Application of L-aspartic acid-beta-hydroxamate in preparation of medicine for treating type 2 diabetes

A technology of aspartic acid and hydroxamic acid, which can be used in drug combinations, metabolic diseases, pharmaceutical formulations, etc., can solve the problems of vitamin B12 deficiency, aggravating cognitive dysfunction in diabetic patients, etc.

Active Publication Date: 2021-09-24
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current drugs for the treatment of type 2 diabetes all have relatively serious side effects. For example, metformin has a strong gastrointestinal stimulating effect, such as nausea, vomiting, diarrhea, and a small number of patients have lactic acidosis. Long-term use of metformin will lead to vitamin B12 deficiency and aggravate diabetes. Patients with cognitive dysfunction, so metformin should be used with caution in patients with diabetic nephropathy; rosiglitazone has certain nephrotoxicity

Method used

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  • Application of L-aspartic acid-beta-hydroxamate in preparation of medicine for treating type 2 diabetes
  • Application of L-aspartic acid-beta-hydroxamate in preparation of medicine for treating type 2 diabetes
  • Application of L-aspartic acid-beta-hydroxamate in preparation of medicine for treating type 2 diabetes

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Several db / db mice were taken and divided into the following groups from the age of 12 weeks:

[0035] 1. Feed normal saline (denoted as db / db+saline, 0.06mL / 10g, 25 rats in total) from the age of 12;

[0036] 2. Feed Metformin (denoted as db / db+Met, 250mg / kg, 19 rats in total) from the age of 12;

[0037] 3. From the age of 12, LABH was fed (denoted as db / db+LABH, 20 mg / kg, 22 rats in total).

[0038] Each group was fed once a day according to the feeding dose for 18 weeks until the db / db mice were 30 weeks old.

[0039] Within one month after gavage, the wild-type mice (WT, gavage saline 0.06mL / 10g, 14) of the gavage group and the same age as db / db mice were checked once a week for random blood glucose, and the drug was gavaged for one month Afterwards, check random blood sugar every two weeks. The test results are shown in Table 1 and figure 1 as shown, figure 1 The statistical markers in the corresponding colors are the comparisons between the metformin group o...

Embodiment 2

[0044] Several WT mice and db / db mice were taken and divided into the following groups from the age of 12 weeks:

[0045] 1. Feed normal saline (denoted as db / db+saline, 0.06mL / 10g, 8 rats in total) from the age of 12;

[0046] 2. Feed Metformin (denoted as db / db+Met, 250mg / kg, 6 rats in total) from the age of 12;

[0047] 3. Feed LABH (denoted as db / db+LABH, 20mg / kg, 10 rats in total) from the age of 12;

[0048] 4. WT mice (10) did not receive any treatment.

[0049] Once a day, fed for 18 weeks, continued until the 30th week of age. After the experiment, blood was taken to detect the content of glycosylated hemoglobin, and the test results are shown in Table 2 and figure 2 as shown, figure 2Medium **p<0.01.

[0050] Table 2 Effects of different drugs on glycosylated hemoglobin in db / db mice (nmol / L)

[0051] average value SEM WT 582.0842 37.37315 db / db+saline 877.9364 56.19169 db / db+LABH 572.363 56.28566 db / db+Met 561.2123 4...

Embodiment 3

[0054] Glucose Tolerance Test (OGTT)

[0055] The 11-week-old WT mice and db / db mice were fed with glucose to detect the glucose tolerance of the mice. After fasting overnight, each mouse was fed with glucose 2g / kg. Blood glucose was detected in 30 minutes, 60 minutes, 90 minutes, and 120 minutes. The statistical results of the glucose tolerance of WT mice and db / db mice are shown in Table 3 and image 3 as shown, image 3 Moderate ***p<0.001.

[0056] Before table 3 administration, WT mice and db / db mice are to the degree of glucose tolerance (mg / dL)

[0057]

[0058] Several WT mice and db / db mice were taken and divided into the following groups from the age of 12 weeks:

[0059] 1. Feed normal saline (denoted as db / db+saline, 0.06mL / 10g, 21 rats in total) from the age of 12;

[0060] 2. Feed Metformin (denoted as db / db+Met, 250mg / kg, 20 rats in total) from the age of 12;

[0061] 3. Feed LABH (denoted as db / db+LABH, 20mg / kg, 22 rats in total) from the age of 12;

...

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Abstract

The invention belongs to the technical field of medicine application, and particularly relates to application of L-aspartic acid-beta-hydroxamate in preparation of a medicine for treating type 2 diabetes. The invention provides the application of the L-aspartic acid-beta-hydroxamate in preparation of the medicine for treating diabetes. According to the present invention, L-aspartic acid-beta-hydroxamate (LABH) is a reversible serine racemase (SR) inhibitor, and inhibits the catalytic reaction of the SR by competing with pyridoxal for binding sites. In the application of the L-aspartic acid-beta-hydroxamate, the L-aspartic acid-beta-hydroxamate can effectively reduce the content of random blood glucose and glycosylated hemoglobin of db / db mice, improve glucose tolerance and improve insulin sensitivity.

Description

technical field [0001] The invention belongs to the technical field of drug application, in particular to the application of L-aspartic acid-β-hydroxamic acid in the preparation of drugs for treating type II diabetes. Background technique [0002] Type 2 diabetes is a metabolic disease, manifested as high sugar, high insulin, insulin resistance, and even develops to high blood pressure and high blood fat, which seriously endangers the health of adults. The current strategies for the treatment of type Ⅱ diabetes include: behavioral therapy, diet control and drug therapy. Currently, the most common first-line drugs for the treatment of type 2 diabetes include metformin and rosiglitazone. However, the current drugs for the treatment of type 2 diabetes all have relatively serious side effects. For example, metformin has a strong gastrointestinal stimulating effect, such as nausea, vomiting, diarrhea, and a small number of patients have lactic acidosis. Long-term use of metformi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/198A61P3/10
CPCA61K31/198A61P3/10
Inventor 吴圣洲江海燕江雪周翩丝瞿佳
Owner WENZHOU MEDICAL UNIV
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