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Acid-resistant glycolipid modified liposome and application thereof

A liposome and acid-resistant technology, applied in the field of biological preparations, can solve problems such as limited application of liposomes, achieve good gastric retention effect, good penetration effect, and the effect of eradicating Helicobacter pylori infection

Pending Publication Date: 2022-07-29
OCEAN UNIV OF CHINA +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the instability of liposomes in the external environment limits their application as oral formulations

Method used

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  • Acid-resistant glycolipid modified liposome and application thereof
  • Acid-resistant glycolipid modified liposome and application thereof
  • Acid-resistant glycolipid modified liposome and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Example 1. Preparation and characterization of surfactant-modified liposomes

[0055] 1. Preparation and characterization of empty liposomes

[0056] (1) Construction of Liposome Skeleton (LipoSC)

[0057] Soybean lecithin (SL) and cholesterol (Chol) were dissolved in chloroform according to different mass ratios (1: 1, 2: 1, 3: 1, 4: 1, 5: 1) in a water bath at 70 °C in a fume hood. Chloroform was evaporated under conditions for 5 min to form a thin lipid layer. Pure water was added as the aqueous phase, and the lipid layer was resuspended using an ultrasonic cleaner to obtain a crude liposome solution of 1 mg / mL. The obtained crude liposome suspension was sonicated for 10 min in an ice-water bath (2 s work, 2 s interval, 40% power) to obtain the final liposome suspension. The particle size and polymer polydispersity index (PDI) of liposomes prepared with different mass ratios of soybean lecithin and cholesterol were detected by Malvern particle size analyzer.

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Embodiment 2

[0104] Example 2. Performance evaluation of LipoSC-MELB4 for gastric drug delivery system

[0105] 1. In vitro evaluation of the bacteriostatic effect of free AMX and LipoSC-MELB4 / AMX

[0106] The bacteriostatic effect of free AMX and LipoSC-MELB4 / AMX was evaluated by broth dilution method. Helicobacter pylori was cultured on BHI solid blood plate, and the strains were taken from the laboratory strain library.

[0107] Resuspend well-viable H. pylori in liquid sterile BHI medium containing 5% fetal bovine serum and 0.2% DENT, adjust OD by UV spectrophotometer 600 = 0.1. After the drug is diluted in a sterile 96-well plate, the Helicobacter pylori suspension is inoculated into the 96-well plate and mixed with it, so that the final concentration of the drug in each well reaches a preset concentration. The wells that only added liquid BHI medium or Helicobacter pylori suspension were set up as controls. The above operations are all performed in a sterile operating table. The...

Embodiment 3

[0145] Example 3. Evaluation of the therapeutic effect of LipoSC-MELB4 / AMX on Helicobacter pylori-infected mice

[0146] 1. Establishment of gastric ulcer model in mice

[0147] Mice were housed in a controlled environment with temperature (27 ± 2 °C) and humidity (72 ± 5%). During the experiment, the weight changes of the mice in each group were observed and recorded. The mice in the experimental group first formed a gastric ulcer model by water immersion to help the infection of Helicobacter pylori in the gastric mucosa.

[0148] Method for establishing gastric ulcer model: After the mice fasted for 12 hours, the limbs of the mice were bound on a wooden board, and water was added to the xiphoid process for 3 hours, and the water temperature should not be too cold. After the experiment, the mice were unbound and returned to the group mouse cages, and the experiment was repeated every other day. This was repeated three times to ensure the formation of ulcers in the stomach of...

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Abstract

The invention discloses an acid-resistant glycolipid modified liposome and an application thereof. The glycolipid modified liposome is prepared from soybean lecithin, cholesterol and glycolipid according to the mass ratio of (1-5): 1: (1-5), has acid resistance, can tolerate the pH of 3.0-7.0, is good in dispersity and has the particle size of 70-90 nm. The lipid-modified liposome can directly remove a helicobacter pylori biological membrane. The invention also verifies that by using the glycolipid modified lipidosome to wrap antibiotics, effective and continuous slow release of drugs in a gastric acid environment can be realized, and the glycolipid modified lipidosome has the functions of gastric retention, mucous barrier penetration and helicobacter pylori biological membrane, so that the bioavailability of amoxicillin is remarkably improved. Helicobacter pylori infection can be eradicated, and treatment of helicobacter pylori related gastritis and gastric ulcer is promoted.

Description

technical field [0001] The invention belongs to the field of biological preparations, in particular to an acid-resistant glycolipid modified liposome and an application thereof. Background technique [0002] Helicobacter pylori is a Gram-negative, spiral-shaped, microaerophilic, polyflagellated bacterium. Helicobacter pylori infection is closely associated with a variety of gastric diseases, including gastritis, peptic ulcer and gastric cancer. Due to the increasing drug resistance of Helicobacter pylori, the low compliance of patients with antibiotic therapy, and the instability of the drug in the gastric acid environment, the standard triple therapy or bismuth quadruple therapy commonly used in clinical practice is not effective for Helicobacter pylori. The eradication rate of infection has gradually decreased, and the recurrence rate has increased significantly, so there is an urgent need to find novel antibacterial strategies for H. pylori. [0003] Nano-drug carriers ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/54A61K31/43A61K47/24A61K47/28A61P1/04A61P31/04
CPCA61K47/6911A61K47/549A61K31/43A61K47/24A61K47/28A61P31/04A61P1/04Y02A50/30
Inventor 刘晨光杨莹池哲吴艳平于钰丁松
Owner OCEAN UNIV OF CHINA
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