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Polypeptides and composition thereof for treating metabolic system diseases

A composition and mixture technology, applied in the field of biomedicine, can solve problems such as hypoglycemia, nausea and vomiting of patients, and bone loss, and achieve long-term stable storage, excellent hypoglycemic and blood lipid-lowering activities, and convenient and safe medication

Active Publication Date: 2018-10-23
WUHAN GRECTTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These existing medicines all have obvious disadvantages, such as metformin, which can easily lead to lactic acidemia, thiazolidinediones, which have side effects such as liver toxicity and bone loss, and long-term use of sulfonylureas, which can easily cause hypoglycemia, and long-term use DD-IV inhibitors are prone to coughing, GLP-1 is likely to cause nausea and vomiting in patients, and insulin has a series of problems such as inability to take orally, inconvenient storage and use, hypoglycemia in patients, insulin resistance and subcutaneous fat atrophy caused by long-term use
[0006] At present, the hypoglycemic drugs used clinically have various defects, and they cannot cure diabetes. Diabetics' needs

Method used

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  • Polypeptides and composition thereof for treating metabolic system diseases
  • Polypeptides and composition thereof for treating metabolic system diseases
  • Polypeptides and composition thereof for treating metabolic system diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0151] Embodiment 1 extracts polypeptide of the present invention from leguminous plant

[0152] The polypeptides of the present invention can be extracted from the seeds of leguminous plants or soybean meal, a by-product of processing. The specific extraction process is as follows:

[0153] Take 10 kg of commercial pea soybean meal, pulverize it with a pulverizer, and sieve it to obtain particles with an average particle size of 100 mesh, mix it with 50 liters of chloroform, stir for 1 hour, centrifugally filter, wash the filter cake with chloroform, and obtain decolorized and degreased soybean meal after drying.

[0154] The above-mentioned decolorized and defatted soybean meal was mixed with 100 liters of n-butanol, homogenized by a homogenizer for 30 minutes, connected to a freezer to control the working temperature at 10°C, then transferred to a jacketed extraction tank, stirred for 24 hours at 10°C, and centrifuged to obtain The supernatant, the filter cake was washed w...

Embodiment 2

[0171] Embodiment 2 Utilizes the solid-phase polypeptide synthesis method to synthesize the polypeptide of the present invention

[0172] The polypeptide of the present invention can also be synthesized by a solid-phase polypeptide synthesis method, and the specific process is as follows:

[0173] Use the ABI 433A type peptide synthesizer of Applied Biosystems, adopt the Fmoc / tBu method, NMP solvent system, HBTU / HOBt as the condensation agent, the groups used to protect the amino acid side chains are: Ser, Thr and Tyr use tert-butyl (tBu ), Asp and Glu use tert-butyl ester group, Asn, Gln and Cys use trityl (Trt), Arg uses 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfone Acyl (Pbf), Lys uses 2-chlorobenzyloxycarbonyl. The synthesis scale is 0.5 mmol, and the amino acid with protective group and condensing agent are in excess of 10 times, and it is automatically completed after the program is set. After the reaction was completed, the resin was washed three times with DCM, va...

Embodiment 3

[0189] Example 3 Normal mouse tail vein injection polypeptide hypoglycemic effect experiment of the present invention

[0190] 1. Materials and Instruments

[0191] Polypeptide: the polypeptide of SEQ ID No.7 in embodiment 1, average molecular weight 3789, aminoacid sequence is ASCNGVCSPFEMPPCGTSACCRCIPVGLFIGYCRNPSG (see figure 2 ), HPLC purity ≥ 98%, is prepared into the solution of 1mg / ml with normal saline for subsequent use;

[0192] Kunming white mice: Hubei Provincial Health and Epidemic Prevention Station, 40, weighing 20±2g, male;

[0193] Blood glucose tester and test strips: Beijing Yicheng Medical Co., Ltd.;

[0194] 2. Experimental method

[0195] The above-mentioned mice were fasted for 4 hours (without water) and randomly divided into 4 groups, 10 mice in each group. Each mouse was stained with picric acid as a marker, and the tail vein blood was taken to measure blood sugar. The blank control group was given normal saline 0.05ml / 10g rat tail vein injection ...

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Abstract

The invention provides a polypeptide with excellent activities, after combination with amino acids, the stability is improved, and the hypoglycemic and lipid-lowering activities are improved. The polypeptide and a composition thereof with the amino acids are resistant to pepsin and trypsin hydrolysis, so that the polypeptide and the composition can be administered orally and injected intravenously, intramuscularly or subcutaneously. The polypeptide and the composition are rare hypoglycemic and hypolipidemic medicines that can be used by four administration modes. The polypeptide and the composition are flexible in medication modes, have the function of protecting and repairing pancreatic beta cells, do not cause hypoglycemia reaction and insulin resistance in patients, have no toxic and side effects, are convenient and safe to use, can be stored stably for a long time, and can effectively prevent and treat type 2 diabetes diabetes and hyperlipidemia. Compared with the existing hypoglycemic drugs, the polypeptide and the composition can effectively reduce glycated hemoglobin of the diabetic patients, and has obvious advantages of additional cardiovascular benefits and reduction of diabetic complications.

Description

technical field [0001] The invention belongs to the field of biomedicine, relates to a polypeptide and its composition, in particular to a polypeptide and its composition for treating metabolic system diseases. Background technique [0002] Diabetes mellitus is a comprehensive metabolic system disease caused by the relative or absolute deficiency of insulin secretion in the body, the inability of insulin to play a normal physiological role in the target cells and / or the excessive secretion of glucagon. The basic feature is that the patient has chronic hyperglycemia. [0003] The main hazard of diabetes is the complications of diabetes. Long-term diabetes will damage multiple systems of the body, especially the cardiovascular system, leading to chronic progressive lesions in the eyes, kidneys, nerves, heart, blood vessels and other tissues, causing functional defects and failure, such as Cardiovascular and cerebrovascular arteriosclerosis, retinal and renal microvascular les...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/16A61P3/10A61P3/06A23L33/185
CPCA61K38/168A23V2002/00A61K45/06A61K9/0019A23L33/18A23L33/105A61K38/28A61K36/48A61K2300/00A23V2200/328A23V2250/21A23V2250/55A23L33/185A61K38/16A61P3/06A61P3/10C07K14/415A61K38/22A61P3/00A61P3/08A61K31/198A61K9/0056A61K47/02A61K47/10A61K47/12A61K47/183A61K47/26A61K47/42
Inventor 张宇飞
Owner WUHAN GRECTTECH CO LTD
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