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Method for preparing nanoliposomes by supercritical CO2 fluid

A nano-liposome and supercritical technology, which is applied in the direction of liposome transportation, can solve the problems of limited compatibility and other problems, and achieve the effect of good affinity, uniform particle size distribution and narrow particle size distribution

Inactive Publication Date: 2013-02-27
SHENZHEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, limited by supercritical CO 2 With the compatibility problem of water, purely utilize RESS technology to reduce liposome particle diameter and also have certain limitation, the average particle diameter of prepared liposome is about 100nm, as further reducing the particle diameter of liposome, until Below 50nm, there are still some difficulties

Method used

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  • Method for preparing nanoliposomes by supercritical CO2 fluid
  • Method for preparing nanoliposomes by supercritical CO2 fluid
  • Method for preparing nanoliposomes by supercritical CO2 fluid

Examples

Experimental program
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Effect test

Embodiment 1

[0029] Preparation and determination of embodiment 1 nano liposome

[0030] 1. Preparation of Nanoliposomes

[0031] Phosphatidylcholine, provided by Shanghai Bioengineering Company;

[0032] Experimental device: Jiangsu Hua'an supercritical reaction device, in which the rapid expansion part is designed and manufactured by the Modern Technology Center of South China University of Technology. The capacity of the reactor is 1L, the capacity of the collection tank is 2L, the maximum pressure is 35MPa, and the maximum temperature is 368K.

[0033] Preparation method: In one embodiment, the method for preparing nanoliposomes of the present invention can be carried out in supercritical CO 2 Completed in the reaction device, the flow chart is as follows figure 1 shown. The specific steps are: mix 22g of phosphatidylcholine [x(PC)=1.7×10 -3 ] dissolved in 150mL ethanol [x(CH 3 CH 2 OH)=1.5×10 -1 ], inject CO 2 In the fluid reaction kettle 6, inject 500 mL of PBS buffer solutio...

Embodiment 2

[0038] The impact of embodiment 2 phospholipid dosage on liposome formation

[0039] This embodiment investigates and forms the required phospholipid consumption of microemulsion [phospholipid is in supercritical CO 2 Effect of mole fraction, x(PC)] on the formation of nanoliposomes. Control x(PC) is 3.8×10 -4 ~2.3×10 -3 , the amount of ethanol and water is set to x(CH 3 CH 2 OH)=1.5×10 -1 with x(H 2 O)=1.5×10 -1 , at a pre-expansion pressure of 25MPa and a pre-expansion temperature of 333K for 2h. The formed supercritical microemulsion was sprayed into the buffer solution at 2L / min, and the prepared liposome suspension was collected. According to the method and parameters of Example 1, the average particle size and particle size distribution of the prepared liposomes were measured, and the results are shown in Table 1.

[0040] The influence of table 1 phospholipid dosage on nano liposome preparation

[0041]

[0042] The results of this example show that when ...

Embodiment 3

[0043] The influence of embodiment 3 distilled water consumption on liposome formation

[0044] This example examines the amount of water required to form a microemulsion [x(H 2 O)] on liposome formation. Control x(PC)=1.7×10 -4 , the amount of ethanol is x(CH 3 CH 2 OH)=1.5×10 -1 , the amount of distilled water x(H 2 O) is 0~3.1×10 -1 , at a pre-expansion pressure of 25MPa and a pre-expansion temperature of 333K for 2h. Formation of supercritical microemulsion CO 2 Spray into the buffer solution at a speed of 2L / min, and collect the prepared liposome suspension. According to the method and parameters of Example 1, the average particle size and particle size distribution of the prepared liposomes were measured, and the results are shown in Table 2.

[0045] The impact of the amount of water required for the formation of table 2 microemulsions on the preparation of nanoliposomes

[0046]

[0047] The results of this example show that distilled water can 2 The mo...

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Abstract

The invention discloses a method for preparing nanoliposomes by supercritical CO2 fluid, which comprises the following steps of: (1) dissolving a certain amount of lipid membrane materials and cosurfactant into supercritical CO2 in a supercritical reaction kettle, and solubilizing a certain amount of distilled water to form a supercritical micro-emulsion; (2) pre-expanding the supercritical micro-emulsion under set pressure and temperature and then rapidly jetting into a water phase medium in a supercritical collection kettle through a nozzle at a certain flow velocity, and dispersing and settling out to form liposome mixed suspension liquid; and (3) continuously dissolving CO2 through the supercritical collection kettle and removing residual ethanol in the liposome mixed suspension liquid, metering by a rotor metering gauge and evacuating, and collecting the liposome mixed suspension liquid in the supercritical collection kettle. In the technology, the micro-emulsion of the lipid membrane materials formed in the supercritical CO2 is used as a template for assembling the lipid, and the lipid is collected by using the supercritical rapid expansion technology so as to provide a new path for preparing the nanoliposomes.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a method for preparing nano liposomes by a supercritical microemulsion coupling rapid expansion technology. Background technique [0002] Nanoliposomes are small unilamellar vesicles (SUVs) with a particle size of less than 100 nm prepared by encapsulating drugs in phospholipid bilayers using phospholipids as drug carriers. Compared with ordinary liposomes, nano-liposomes have outstanding nano-effects, namely small size effects and surface effects, which are conducive to improving the bioavailability and absorption stability of insoluble drugs, improving the targeting effect of drugs, reducing or Reduce drug damage to normal tissues, especially suitable for injection administration. [0003] The preparation methods adopted by liposomes include film dispersion method, film-ultrasonic dispersion method, melting method, freeze-thaw method, injection method, re...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127
Inventor 文震刘波郑宗坤游新奎蒲一涛刘剑洪
Owner SHENZHEN UNIV
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