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Method for preparing medicine-carrying microvesicle

A drug-carrying and microbubble technology, applied in the field of medicine, can solve the problems of short half-life in vivo, impermeability of lipid microbubbles, low drug encapsulation efficiency and drug-loading capacity, and achieve tumor inhibition, superior chemical selectivity, The effect of mild reaction conditions

Inactive Publication Date: 2011-09-14
CHONGQING MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] The object of the present invention is to provide a new preparation method of drug-loaded microbubbles in view of the defects of the prior art that lipid microbubbles cannot penetrate the vascular endothelial space, the drug encapsulation rate and drug loading capacity are not high, and the half-life in vivo is short.

Method used

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  • Method for preparing medicine-carrying microvesicle
  • Method for preparing medicine-carrying microvesicle
  • Method for preparing medicine-carrying microvesicle

Examples

Experimental program
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Effect test

Embodiment 1

[0041] (1) Preparation of ordinary lipid microbubbles:

[0042] Distearoylphosphatidylcholine and DSPE-PEG(2000)-NH 2 , Glycerol with a volume ratio of 1:2 was added to a plastic vial and mixed with PBS buffer, distearoylphosphatidylcholine and DSPE-PEG(2000)-NH 2 The ratio of the sum of the mass of glycerol and the sum of the volumes of glycerol and PBS is 6:1 in mg / ml. After heating in a water bath at 35°C for 30 minutes, replace the air in the small tube with perfluoropropane gas, and mechanically shake with an amalgam capsule blender Lipid microvesicles were produced after 40s. Morphological distribution of common lipid microvesicles, see figure 1 . From figure 1 It can be seen that the ordinary lipid microbubbles have uniform particle size and good dispersion.

[0043] (2) Preparation of drug-loaded polymer nanoparticles:

[0044] Dissolve 40 mg of PLGA (PLGA with carboxyl groups, molecular weight 25000, polymerization ratio 50:50) in 1 ml of dichloromethane as the ...

Embodiment 2

[0052] (1) Preparation of ordinary lipid microbubbles:

[0053] Distearoylphosphatidylcholine and DSPE-PEG(2000)-NH with a mass ratio of 3:1 2 , glycerol and PBS buffer solution in a volume ratio of 1:4 were mixed in a plastic vial, and the distearoylphosphatidylcholine and DSPE-PEG(2000)-NH 2 The ratio of the sum of the mass of glycerol and the sum of the volumes of glycerol and PBS is 3:1 in mg / ml. After heating in a water bath at 40°C for 40 minutes, replace the air in the small tube with hexafluoropropane gas, and mechanically shake with an amalgam capsule blender Lipid microbubbles were prepared after 50 s, and the prepared lipid microbubbles had uniform particle size and good dispersion.

[0054] (2) Preparation of drug-loaded polymer nanoparticles:

[0055] Dissolve 50 mg of PLGA (PLGA with carboxyl groups, molecular weight 25000, polymerization ratio 50:50) in 1 ml of dichloromethane as the oil phase, add 250 μl of hematoporphyrin hydrochloride aqueous solution to th...

Embodiment 3

[0063] Step (4) is omitted in embodiment 1 and embodiment 2, and all the other operations are the same as embodiments 1 and 2. After centrifugation and rinsing for 3-5 times, the negatively charged PLGA nanoparticles on the surface of the unactivated carboxyl groups did not significantly combine with the positively charged lipid microbubbles on the surface. The results are shown in Figure 4 . It shows that the combination of the two in Example 1 and Example 2 mainly depends on chemical covalent coupling rather than pure electrostatic adsorption.

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Abstract

The invention relates to the field of medicines, in particular to a medicine-carrying microvesicle and a preparation method thereof. In the method, medicine-carrying high molecular polymer class nano particles are connected with a lipid microvesicle by an amido bond so as to prepare the medicine-carrying microvesicle. Under an ultrasonic action, the lipid microvesicle of the medicine-carrying microvesicle is broken, and the medicine-carrying high molecular polymer class nano particles which are connected with the lipid microvesicle of the medicine-carrying microvesicle are released and enter the clearances of tissues to exert an action. The method has mild reaction conditions and superior chemical selectivity of the reaction process; and the prepared medicine-carrying microvesicle can be used as an ultrasonic contrast agent, can also be used as a controlled release carrier for various medicines and has extensive application prospect.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a method for preparing drug-loaded microbubbles. Background technique [0002] Tumor is one of the three major diseases that seriously threaten human health today. Most of the conventional chemotherapeutic drugs widely used in clinical tumor treatment are non-selective drugs, which can kill normal cells as well as tumor cells, and conventional therapeutic doses can produce significant toxic and side effects on normal tissues and organs, causing patients Can not tolerate, reduce drug efficacy. Therefore, the key to the development of anticancer drugs is to improve the tumor selectivity of drugs and reduce their aggregation in non-targeted sites. [0003] In recent years, with the development and infiltration of molecular pharmacology, biopharmaceutical analysis, cell medicinal chemistry, drug molecular delivery and systems engineering, and the continuous emergence of new technologies, th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/00A61K47/34A61K47/24A61P35/00
Inventor 冉海涛郑元义王志刚张亚萍郝兰李攀张辉
Owner CHONGQING MEDICAL UNIVERSITY
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