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Preparation of gas containing lipid body and composite granule

A technology of composite particles and liposomes, which is applied in the directions of liposome delivery, preparations for in vivo tests, and pharmaceutical formulations, which can solve the problem of difficult application of contrast agents, difficulty in controlling gas velocity and uniformity, and gas-containing liposomes. Reduce the stability and other problems, to achieve the effects of improving sensitivity and imaging quality, good ultrasonic reflection characteristics, and simple and easy preparation methods

Inactive Publication Date: 2005-02-23
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the liposome is only used in contrast-enhanced ultrasound, and has no application in other medical imaging such as computer-aided tomography (CT)
At the same time, it has not been combined with ultrasound-mediated gene delivery to optimize the lipid composition, concentration, and dosage ratio of gas-containing liposomes and other important parameters
Among them, although the decompression method and physical stirring method are widely used, the method is convenient, but the carrier gas is limited and it is difficult to control the speed and uniformity of gas generation; when the gas carried is air, because the air is easy to permeate the lipid membrane, the The stability of gas-containing liposomes is reduced; switching to fluoroalkane can effectively prolong the stability time, but obviously the cost is greatly increased, and it is difficult to apply to the field that requires a large amount of contrast agent
Moreover, for the application of targeted drug delivery, the drug loading capacity of the existing preparation methods is very limited

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1, and preparation 10nm, application 。 Embodiment approach

[0016] (1) dissolving soy lecithin and cholesterol in an organic solvent with a molar ratio of 3:1, removing the organic solvent, and dispersing to form a film;

[0017] (2) the lipid film prepared by step (1) is hydrated with a concentration of carbonate and / or bicarbonate ion solution of 0.005 mol / liter, dispersed, and made into a liposome suspension with a concentration of 20mg / ml , high pressure homogenization, to obtain a liposome solution with an average particle size of about 5nm;

[0018] (3) Dialysis removes free carbonate and / or bicarbonate ions, and adding hydrogen ion concentration to the liposome suspension prepared in step (2) is an aqueous solution of 0.001 mol / liter, mixes and places, that is Liposomes containing carbon dioxide gas can be obtained.

[0019] (4) Add an appropriate amount of alkaline substances to adjust the pH as required, and the average particle size measured by a dynamic laser particle size analyzer is 10 nm.

[0020] (5) Observing the ultr...

Embodiment 2

[0021] Example 2, after embedding a water-insoluble compound in liposomes, the gas-containing liposomes with an average particle size of 10 μm are prepared by adjusting the pH value of the solution. The preparation method is as follows:

[0022] (1) dissolving soybean lecithin and cholesterol in an organic solvent with a molar ratio of 4:1, removing the organic solvent, and dispersing to form a film;

[0023] (2) hydration of 3 milliliters of calcium chloride solution of 1.35 mol / liter by the lipid film that step (1) is made with concentration, disperse, freeze-thaw 3 times, make the multilamellar liposome that concentration is 20mg / ml liposome suspension

[0024] (3) Dialysis removes free calcium chloride, and in the liposome suspension prepared in step (2), gradually adding concentration is 3 milliliters of sodium carbonate solution of 1 mol / liter, mixes and places, for subsequent use.

[0025] (4) after dialysis removes free carbonate ion, in the liposome suspension that i...

Embodiment 3

[0026] Embodiment 3, the preparation of gas-containing liposome solution and its effect of reducing the CT value of aqueous solution, the preparation method is as follows:

[0027] Weigh 100 mg of lipid mixture of lecithin: cholesterol = 4: 1 (molar ratio), dissolve it in 5 ml of chloroform, evaporate in a water bath at 30 degrees Celsius, remove chloroform, and form a film; add 5 ml of 0.5 mol / liter aqueous sodium bicarbonate solution to hydrate , and use ultrasonic dispersion to obtain a translucent liposome suspension with an average particle size of about 80nm; after dialysis to remove free sodium bicarbonate, add 5 ml of 0.2 mol / liter citric acid aqueous solution, shake gently, and mix well Afterwards, CT tomography was performed to measure the CT value.

[0028] The results showed that the density of the prepared gas-containing liposomes was constant within 4 hours, and the CT value was about -40HU. Measure the CI value of the sodium bicarbonate aqueous solution of 0.5 ...

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Abstract

A process for preparing the gas-contained lipid or gas-contained composite lipid particles includes such steps as preparing the suspension of lipid or composite lipid particles from one or more ions, removing free ions, adding another solution of one or more ions to be reacted, regulating temp and pH value, mixing, and chemical reacting, another process is also disclosed.

Description

technical field [0001] The invention relates to a method for preparing composite particles, in particular to a method for preparing gas-containing liposomes and gas-containing lipid complexes based on chemical reactions in microspaces. Used in the field of biomedical technology. Background technique [0002] With the increasing development of ultrasound medicine, gas-containing particles with specific response characteristics to ultrasound have been widely used in biomedicine, including medical image enhancement, drug and gene targeted delivery, etc. At present, the most widely used gas-containing particles are albumin as a carrier, and the gases carried by them are usually air, nitrogen and fluorinated alkanes, and are widely used as ultrasound contrast agents. However, the second-generation ultrasound contrast agents represented by Aerosome gas-containing liposomes have also received great attention. At the same time, gas-containing microbubbles also have potential appli...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K49/00A61K49/18
Inventor 徐宇虹魏晓慧冯海
Owner SHANGHAI JIAO TONG UNIV
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