Hypoglycemic peptide and drug use thereof

A hypoglycemic and drug technology, applied in the field of medicine, can solve problems such as serious adverse reactions, inconvenient insulin administration, hypoglycemia, etc., and achieve the effect of avoiding gastrointestinal digestion and helping gastrointestinal absorption.

Active Publication Date: 2014-03-19
山东康泽健康管理咨询有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Traditional antidiabetic drugs have their own disadvantages
Insulin administration is inconvenient and can easily cause hypoglycemia; insulin secretagogues such as sulfonylureas, repaglinide, and nateglinide can be taken orally, but they depend on the existence of residual pancreatic β cells and are likely to cause hypoglycemia. Secondary failure often occurs; severe adverse reactions of metformin; α-glucosidase inhibitors and thiazolidinediones cannot fundamentally lower blood sugar
The newly launched glucagon-like peptide-1 (glucose-like peptide-1, GLP-1) analogues have excellent effects on type Ⅱ diabetes mellitus, which are not well cured by traditional hypoglycemic drugs, but are unstable in nature and require high storage. Short duration of action, requires injection

Method used

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  • Hypoglycemic peptide and drug use thereof
  • Hypoglycemic peptide and drug use thereof
  • Hypoglycemic peptide and drug use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Synthesis of embodiment 1 hypoglycemic peptide

[0058] The hypoglycemic peptide of the present invention was synthesized by the polypeptide solid-phase synthesis method of Jill Biochemical (Shanghai) Co., Ltd. with a polypeptide synthesizer. The peptide synthesis starts from H-Pro-2-Chlorotrityl chloride Resin, using HOBt / DCC as the activator, followed by Fmoc-Gly-OH, Fmoc-Pro-OH, Fmoc-Pro-OH, Fmoc-Pro-OH. After each amino acid reacts, it is fully washed by DMF, piperidine is deprotected by Fmnoc, and the DMF is fully washed again before the next amino acid is connected. After all the synthesis is completed, use TFA:H 2 O:EDT=95:2.5:2.5 (v / v) Cut the hypoglycemic peptide from the resin, precipitate it with glacial ether, wash it, and use a C18 column for RP-HPLC purification. Chromatographic conditions: Xbrige BEH130C18 (4.6×250mm, 5μm), reagent A: 0.1% trifluoroacetic acid in acetonitrile; reagent B: 0.1% trifluoroacetic acid in water. The flow rate is 1.0ml / min, a...

Embodiment 2

[0061] Embodiment 2 animal experiment grouping and administration

[0062] Take 30 KK-Ay mice, half male and half female, the blood glucose of female mice is not lower than 7.8mmol / L, and the blood glucose of male mice is not lower than 11.1mmol / L, and they are randomly divided into 5 groups with SPSS11.0 software, each group has 6 Only, so that there is no significant difference in blood glucose in each group, they are: Group B (model control group), Group C (positive control group), Group D (low-dose hypoglycemic peptide group), group E (medium-dose hypoglycemic peptide group) , Group F (high-dose hypoglycemic peptide group). Another 6 normal ICR mice were selected as group A (normal reference group). Group C was given rosiglitazone 8 mg / kg, and groups D, E, and F were given hypoglycemic peptides 3 mg / kg, 10 mg / kg, and 30 mg / kg, respectively. Groups A and B were given an equal volume of normal saline. All groups were intragastrically administered for 2 weeks.

Embodiment 3

[0063] The effect of embodiment 3 hypoglycemic peptide on the body weight of KK-Ay mice

[0064] Each group of KK-Ay mice described in embodiment 2 weighed once every day, and counted once every 7 days, and each group's body weight was compared with before administration, A,

[0065] The body weights of groups C, D, and E were compared with those of groups B and C, and the trend of body weight changes was observed.

[0066] During the administration, the effect of hypoglycemic peptide on the body weight of KK-Ay mice is shown in Table 1 and image 3 shown.

[0067] Table 1 Effects of hypoglycemic peptides on the body weight of KK-Ay mice

[0068]

[0069] N=6, *P<0.05,**P<0.01. Group A,C,D,E are compared with Group B,respectively.

[0070] It can be seen from the tables and charts that the body weight of each administration group (C, D, E, F) is higher than that of B (model group), and the body weight of group D > group E > body weight of group F tends to appear in the...

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Abstract

The invention provides a hypoglycemic peptide, which is provided with an amino acid sequence as shown in SEQ ID NO: 1. The invention also provides a modified peptide of the hypoglycemic peptide. A chemical group, an amino acid, polypeptide, protein or PEG is connected to the N end, C end or intermediate residue of the hypoglycemic peptide. The hypoglycemic peptide provided by the invention can perfect the glucose tolerance of KK-Ay mice, reinforce the glucose utilization ability of the KK-Ay mice, significantly improve the fasting blood glucose and glucose tolerance of the KK-Ay mice, significantly reduce serum total cholesterol and serum triglyceride, significantly perfect the SOD level, reduce the MDA level and protect the body cells against oxygen free radicals, the hypoglycemic peptide has glucose and lipid reducing functions and can resist metabolic syndrome. The hypoglycemic peptide can be used for preparing drugs or healthcare products for treating and/or preventing diabetes or hyperlipidemia.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a hypoglycemic peptide and its medicinal use. Background technique [0002] Diabetes mellitus (DM) is a metabolic disease characterized by relative or absolute insufficiency of insulin and the main symptom of hyperglycemia. Relative or absolute insufficiency of insulin causes hyperglycemia, which in turn leads to metabolic disorders of the three major nutrients, ultimately affecting patients Normal physiological function and cause complications. There are many types of diabetes, with type 1 diabetes and type 2 diabetes being the most common. Traditional antidiabetic drugs have their own disadvantages. Insulin administration is inconvenient and can easily cause hypoglycemia; insulin secretagogues such as sulfonylureas, repaglinide, and nateglinide can be taken orally, but they depend on the existence of residual pancreatic β cells and are likely to cause hypoglycemia. Second...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06A61K38/08A61P3/10A61P3/06A23L1/29A23L33/00
Inventor 李谦吴梧桐严国文周文喆
Owner 山东康泽健康管理咨询有限公司
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