Group of polypeptides having percutaneous and transmembrane penetration promoting effect, and applications thereof

A technology that promotes transdermal and permeation effects. It is applied in the direction of peptides, non-active ingredients of polymer compounds, and aerosol delivery. It can solve the problems of a large number of animal samples and poor analysis stability, so as to improve the transport capacity and enhance the penetration-promoting activity. , the effect of improving the permeation ability of the skin and transmembrane

Active Publication Date: 2013-06-12
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, the screening method for peptide permeation-enhancing activity mainly adopts in vivo animal experiment method, whi

Method used

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  • Group of polypeptides having percutaneous and transmembrane penetration promoting effect, and applications thereof
  • Group of polypeptides having percutaneous and transmembrane penetration promoting effect, and applications thereof
  • Group of polypeptides having percutaneous and transmembrane penetration promoting effect, and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0012] Diabetic rat model establishment: SD rats were weighed after fasting overnight, and the corresponding streptozotocin was injected according to 70 mg / kg fasting body weight, and the injection was completed within 30 minutes. After about 10 days of modeling, SD rats with a blood sugar level of 20-30 mmol / L were selected for polypeptide screening experiments. Moisten with normal saline and cut off the abdominal hair, so that the exposed area of ​​the rat skin is within 4cm 2 Effect and wash with saline. After transdermal administration, the time-dependent changes in blood sugar in SD rats were observed in vivo and the ability of peptides to promote insulin transdermal penetration was studied, and the transdermal penetration enhancement ability of a series of synthetic peptides was screened.

Embodiment 2

[0014] Caco-2 cell culture method: plant 40-60 generation Caco-2 cells in 25cm 2 in cell culture flasks. DMEM medium contains: 20% bovine serum, 1% (v / v) non-essential amino acids, 2mmol / L L-glutamine, 100IU / mL penicillin, 100μg / mL streptomycin (pH=7.4). Culture conditions are 37°C, 5% CO 2 , 95% air and 90% relative humidity, and the medium was changed three times a week.

Embodiment 3

[0016] Insulin transmembrane transport experiment: Caco-2 cells were seeded in 12-well Transwell culture plates at a seeding density of 2×105 cells / mL. Cell monolayers formed after 20-22 days of culture. Before the transport experiment, the Caco-2 cell monolayer was incubated with HBSS at 37°C for 10 min. At the same time, the resistance value of the cell monolayer membrane is detected to ensure the integrity of the cell membrane. Select a resistance value greater than 400Ω·cm 2 The cell monolayer membrane was used for transport experiments. Add 1.5mL 21IU / mL insulin solution, or 1.5mL 21IU / mL insulin and 5μmol / mL polypeptide (sequence 1-10) solution to the BL side, and add 0.5mL Hank’s solution to the AP side. At different time points (0.5h, 1h, 1.5h and 2h), 100 μL of the receiving solution was drawn from the AP side and the transmembrane resistance of the cell monolayer was detected, and the insulin concentration in the receiving solution was detected by HPLC. Observe t...

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Abstract

The invention discloses a group of polypeptides having a percutaneous and transmembrane penetration promoting effect, and applications thereof, and is suitable for the fields of transdermal and transmembrane drug delivery systems and cosmetics. Each of the polypeptides has eleven amino acid residues, and has an annular structure formed by nine amino acid residues and a disulfide bond, and the structure of each of the polypeptides is characterized in that the N-5 and N-6 positions of the N-terminal of each of the polypeptides are alkaline amino acids or the C-terminal is amidated. The polypeptides synthesized through substituting the N-5 or N-6 position of the N-terminal by an alkaline amino acid and C-terminal amidated polypeptides have substantially higher insulin transdermal and transmembrane penetration capabilities than reported polypeptides having penetration promoting activities. The transdermal and transmembrane penetration promoting capabilities of the polypeptides obtained after the simultaneous substitution of the N-5 and N-6 positions of the N-terminal by the alkaline amino acids are further enhanced, the blood sugar reducing effects of diabetic rats are substantially improved through insulin common transdermal drug delivery, the in-vivo blood sugar level of the diabetic rats within 8h after the transdermal drug delivery is reduced to 20-30% of the original level, and the group of the polypeptides disclosed in the invention can be used in solutions, gels and ointments to promote the percutaneous and transmembrane absorption of biological macromolecular drugs comprising insulin, vaccines and the like.

Description

technical field [0001] The invention relates to a group of polypeptides capable of promoting transdermal and transmembrane penetration and applications thereof, which are suitable for the fields of transdermal and transmembrane drug delivery systems and cosmetics. Background technique [0002] Transdermal administration means that the drug passes through the skin at a certain rate, and is absorbed into the body circulation through capillaries to produce drug effects. It also means that the drug is absorbed through the skin and enters the epidermis, dermis or subcutaneous tissue to exert local therapeutic effects. It means that the drug enters the circulatory system through the biomembrane to produce curative effect. Compared with traditional drug delivery methods, it has many advantages: transdermal and transmembrane drug delivery can reduce or avoid the first-pass effect of the liver, reduce toxic and side effects; avoid various factors that affect gastrointestinal absorpti...

Claims

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Application Information

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IPC IPC(8): C07K7/06A61K47/42A61K9/08A61K9/06
Inventor 李晓晖汪晴常明明
Owner DALIAN UNIV OF TECH
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