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Application of ferric iron ferriporphyrin compound in preparation of anti-type-2 diabetes drug

A technology of type 2 diabetes and ferric iron, applied in the direction of drug combination, dipeptide component, tetrapeptide component, etc., to achieve the effect of lowering blood sugar

Active Publication Date: 2013-02-20
吉林省润宝生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] This type of ferric porphyrin and its derivatives-short peptides with peroxidase activity have a strong ability to penetrate the cell membrane to scavenge intracellular free radicals. They have good antioxidant activity and have been obtained in an in vitro cataract-induced model. It has been verified, but the application in the preparation of drugs for the prevention or treatment of type 2 diabetes has not been published in the literature after searching

Method used

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  • Application of ferric iron ferriporphyrin compound in preparation of anti-type-2 diabetes drug
  • Application of ferric iron ferriporphyrin compound in preparation of anti-type-2 diabetes drug
  • Application of ferric iron ferriporphyrin compound in preparation of anti-type-2 diabetes drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1. Effect of D1 to D10 on promoting sugar consumption in C2C12 cells

[0032] After administration, the glucose content in the culture supernatant of differentiated C2C12 cells was determined by the reductase method, and the effect of the drug on promoting the glucose consumption of C2C12 cells was observed.

[0033] experimental method:

[0034] 1. Cell line: C2C12, a mouse skeletal muscle cell line;

[0035] 2. The final concentration of the drug acting on C2C12 cells is 16 μM;

[0036] 3. When the cells proliferate to 80%~90% in the culture flask, digest with 0.25% trypsin, centrifuge, add medium and blow gently to form a cell suspension, count, 10 4 Place each well in a 96-well plate, change the medium every 2 days, add inducing factors to induce C2C12 cells to differentiate into myotube cells when the cell proliferation reaches 70%, change the low-glucose medium overnight, and change the low-glucose medium again the next morning Different drugs were admi...

Embodiment 2

[0043] Example 2 Observation of the effects of D1~D10 drugs on blood sugar in type 2 diabetic rats induced by high fat and STZ

[0044] experimental method:

[0045] After feeding rats with high-fat diet for 4 weeks, 30 mg / kg STZ was injected intraperitoneally twice to prepare diabetes models, and the model rats with fasting blood glucose in the range of 7.8-15.0 were selected into groups, normal control group, model group, insulin treatment group (subcutaneous injection ,3.2U / kg), the drug treatment (subcutaneous injection 0.3mg / kg) group. After subcutaneous injection for 3 weeks, fasting blood glucose, glucose tolerance test, fasting insulin test, fasting cholesterol test, and fasting triglyceride test were performed.

[0046] Experimental results:

[0047] After 3 weeks of subcutaneous injection in each drug group from D1 to D10, the fasting blood glucose in the drug group and insulin group was significantly lower than that in the model group (see Table 2). significantly...

Embodiment 3

[0054] Embodiment 3 toxicity test

[0055] 1. Acute toxicity test

[0056] A single intravenous injection of D4 was given to ICR mice, and the symptoms of poisoning, degree of poisoning, nature, recovery and death were observed to clarify the acute toxicity of the drug and to understand the target organs of acute toxicity. Adverse reaction monitoring provides reference materials.

[0057] experiment method:

[0058] In this experiment, the median lethal dose method was used. There are 7 dosage groups for males and females, and the dosages for each group are 49, 70, 100, 143, 204, 292, 417 mg·kg-1 respectively; 10 mice in each group are administered intravenously, and the administration volume is 0.25ml / 10g, observed for 14 days after administration. The poisoning symptoms, appearance and duration of the animals were observed, the development of the poisoning symptoms, the time of death, and the number of deaths were observed, and the dead animals were autopsyed.

[0059]...

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Abstract

The invention provides application of a ferric iron ferriporphyrin compound in preparation of an anti-type-2 diabetes drug and belongs to the technical field of biological pharmacy. The ferric iron ferriporphyrin compound consists of heme and oligopeptide. A carboxyl of the heme is connected with an amino on a peptide chain through an amido bond to achieve connection of the heme and the oligopeptide. Other type-2 diabetes treating or preventing drugs can be applied to the drug preparation. The ferric iron ferriporphyrin compound serves as a peroxidase stimulant, has small molecular weight, can enter cells to effectively remove internal superoxide, super-oxygen ions and free radicals and has the effects of reducing blood sugar, cholesterol and triglycerides activity.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and particularly relates to a new medical application of ferric porphyrin and its derivatives, and furthermore, an application in the preparation of anti-type 2 diabetes drugs. Background technique [0002] The trivalent iron porphyrin involved in the present invention and derivatives include heme-short peptide, hypoheme-short peptide, microperoxidase with iron porphyrin as a prosthetic group, including cytochrome C (Cyt C) Octapeptide (abbreviation: MP-8), nonapeptide (abbreviation: MP-9), and undecapeptide (abbreviation: MP-11) from hydrolysis. They all contain covalently bound heme and contain a histidine residue in the peptide, and they have been found to be good peroxidase mimetics. [0003] The trivalent iron porphyrin short peptide compound and its synthesis method involved in the present invention can be referred to the Chinese patent (publication number CN1424322A, publicatio...

Claims

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Application Information

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IPC IPC(8): A61K38/08A61K38/05A61K38/07A61K38/10A61P3/10
Inventor 李惟王丽萍于佳一陈立薛辉
Owner 吉林省润宝生物科技有限公司
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