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Oxygen-carrying liposome with low surface tension and preparation method thereof

A liposome and oxygen-carrying technology, applied in the direction of liposome delivery, halogenated hydrocarbon active ingredients, amine active ingredients, etc., can solve high surface tension, difficult alveolar surface spreading, and inability to provide oxygen-carrying lipids problems such as bulk, to achieve the effect of high oxygen content and low surface tension

Inactive Publication Date: 2016-01-13
SHANGHAI NAT ENG RES CENT FORNANOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, liposome-encapsulated perfluorocarbons have been studied to some extent, but it is still not possible to provide an oxygen-carrying liposome that meets clinical needs.
Fluorocarbon liposomes with smaller particle sizes can be prepared by the injection method, but only phospholipids are used as the film-forming substrate, and the obtained liposome solution has a relatively high surface tension, which is difficult to spread on the alveolar surface, thereby limit its application

Method used

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  • Oxygen-carrying liposome with low surface tension and preparation method thereof
  • Oxygen-carrying liposome with low surface tension and preparation method thereof
  • Oxygen-carrying liposome with low surface tension and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0025] Example 1: Preparation of oxygen-carrying liposomes.

[0026] In parts by weight, the formula is as follows:

[0027] 2000 parts of normal saline;

[0028] 200 parts of soybean lecithin;

[0029] Perfluorooctyl bromide 200 parts;

[0030] 1000 parts of dichloromethane;

[0031] 5 parts of palmitic acid;

[0032] 2 parts of tyloxapol.

[0033] Preparation Process:

[0034] (1) In parts by weight, 200 parts of soybean lecithin, 5 parts of palmitic acid, and 2 parts of tyloxapol were dissolved in 2000 parts of ether, and ultrasonically mixed evenly;

[0035] (2) Add 200 parts of perfluorooctyl bromide to the ether solution, and continue to mix evenly by ultrasonic;

[0036] (3) Slowly add the solution obtained in step (2) dropwise to 2000 parts of normal saline, stir the solution (stirring speed is 1000 rpm), and stir until the ether is completely volatilized for about 2 hours. That is, oxygen-carrying liposomes encapsulating perfluorooctyl bromide can be obtained....

Embodiment 2

[0037] Example 2: Preparation of oxygen-carrying liposomes.

[0038] In parts by weight, the formula is as follows:

[0039] 2000 parts of phosphate buffer;

[0040] 200 parts of egg yolk lecithin;

[0041] FC-77 (a mixture of perfluorooctane and perfluorocyclooctyl ether) 200 parts;

[0042] 1000 parts of ether;

[0043] 1 part cetyl alcohol;

[0044] 1 part of tyloxapol.

[0045] Preparation Process:

[0046] (1) In parts by weight, 200 parts of soybean lecithin, 2 parts of cetyl alcohol, and 1 part of tyloxapol were dissolved in 1000 parts of ether, and ultrasonically mixed evenly;

[0047] (2) Add 200 parts of FC-77 (a mixture of perfluorooctane and perfluorocyclohexyl ether) to the ether solution, and continue to mix evenly by ultrasonic;

[0048] (3) Slowly add the solution obtained in step (2) dropwise to 2000 parts of normal saline, stir the solution (stirring speed is 1000 rpm), and stir until the ether is completely volatilized for about 2 hours. That is, oxy...

Embodiment 3

[0049] Example 3 Toxicity evaluation of oxygen-carrying liposomes.

[0050] Take monolayer cultured HEK293 epithelial cells in the logarithmic growth phase, digest the monolayer cultured cells with 0.25% trypsin and 0.025% ethylenediaminetetraacetic acid disodium salt solution, and prepare with DMEM cell culture medium containing 10% fetal bovine serum Single cell suspension, 1×10 per well 4 Cells were seeded in a 96-well plate with a volume of 100 microliters per well, and the culture plate was moved into a carbon dioxide incubator, and cultured overnight at 37°C, 5% carbon dioxide and saturated humidity to allow the cells to adhere to the wall. On the next day, a series of fluorocarbon oxygen-carrying liposome solutions (using the oxygen-carrying liposome prepared in Example 2) with different concentrations were prepared with phosphate-containing solution. Aspirate the culture medium in the culture dish, add the oxygen-carrying liposome solution, incubate at 37°C for differen...

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Abstract

The invention relates to a method for preparing oxygen-carrying liposomes with low surface tension. The specific steps of the method are as follows: first dissolving phospholipid, cholesterol, tyloxapol, cetyl alcohol and palmitic acid in an organic solvent, and mixing uniformly by ultrasonic, then adding fluorocarbon compound in the solution, and continuing to mix uniformly by ultrasonic. The obtained mixed solution is slowly added dropwise into the saline solution, and the solution is stirred until the organic solvent is completely volatilized, and then oxygen-carrying liposomes encapsulating fluorocarbons can be obtained. The oxygen-carrying liposome prepared by the invention has a relatively low surface tension, which is convenient for spreading in the pulmonary administration and increases the contact area. It can be applied in emergency oxygen supply medicine, acute blood supply, etc.

Description

technical field [0001] The invention belongs to the field of preparation of nanometer materials, and relates to a water-soluble nanoscale oxygen-carrying liposome and its preparation technology. technical background [0002] Perfluorocarbons are a class of compounds obtained by replacing hydrogen atoms in hydrocarbons with fluorine atoms. They are generally colorless and transparent liquids at room temperature, with high density, stable properties, and are not prone to metabolic decomposition. They have the function of fully carrying oxygen and carbon dioxide. It is an ideal liquid breathing medium. Using the intrapulmonary route, it can provide treatment for acute respiratory distress, emergencies and other situations. [0003] Using direct liquid ventilation, that is, directly injecting oxygenated fluorocarbons into the lungs for gas exchange, although it can improve the lung compliance and oxygenation of patients with respiratory distress, it is likely to cause additiona...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K47/10A61K47/12A61K31/035A61K31/03A61K31/13A61K31/02A61K31/131A61K31/4375A61K31/47A61K31/40
Inventor 刘璐魏岱旭朱君王丹
Owner SHANGHAI NAT ENG RES CENT FORNANOTECH
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