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Composite nanometer lipid drug delivery system and therapeutic effect thereof on gynecologic tumor

A drug delivery system and nanolipid technology, applied in gene therapy, antitumor drugs, liposome delivery, etc., can solve the problems of easy leakage of liposomes, reduction of drug loading, and weakening of liposome therapeutic effects.

Active Publication Date: 2019-03-05
RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] However, liposomes have the disadvantage of easy leakage, which leads to reduced stability of liposomes, reduced drug loading, and ultimately weakens the therapeutic effect of liposomes.

Method used

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  • Composite nanometer lipid drug delivery system and therapeutic effect thereof on gynecologic tumor
  • Composite nanometer lipid drug delivery system and therapeutic effect thereof on gynecologic tumor
  • Composite nanometer lipid drug delivery system and therapeutic effect thereof on gynecologic tumor

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preparation example Construction

[0086] The invention provides a kind of preparation method of composite nano liposome, described method comprises:

[0087] (i) providing (a) paclitaxel as a first active ingredient; (b) a target inhibitory miRNA as a second active ingredient; and (c) a lipid material;

[0088] (ii) The components (a), (b) and (c) are compounded to form a composite nano-lipid drug delivery system containing composite liposomes, wherein the average particle diameter of the composite liposomes 10-1000nm.

[0089] In a preferred embodiment of the present invention, the lipid material encapsulates the active ingredient to make a composite liposome, and then adds calcium and phosphorus to make a composite nanoliposome (or a liposome containing the given liposome). drug system).

[0090] In another preferred embodiment of the present invention, in the described composite nano-lipid drug delivery system, the anti-tumor active substance or anti-tumor active substance and energy The total content of...

Embodiment 1

[0121] Preparation of Calcium Phosphorous Composite Liposomes Encapsulating Paclitaxel (PTX)

[0122]Dissolve 150mg PC and 30mg CHOL in 1.5ml of 5mg / ml PTX in dichloromethane, dissolve 30mg (about 1:50 molar ratio to PC) mPEG-HA-PC in 15ml water, add to the above solution for ultrasonic emulsification (2s- 2s-60 times, power 200W, ice bath), decompress and extract the organic solvent. CaP compounding was carried out according to the ratio of 2ml liposome-36μl 2M calcium chloride solution-450μl 1.6mM sodium phosphate solution. Add 2M calcium chloride solution dropwise under stirring first, then add sodium phosphate solution dropwise after stirring for 5 minutes, and continue stirring for 30 minutes to obtain the product.

[0123] The particle diameter of the composite liposome prepared by the present embodiment is as follows: figure 1 shown. The average particle size is 184.5nm, the polydispersity coefficient is 0.215, the encapsulation efficiency is >95%, and the drug load...

Embodiment 2

[0125] Preparation and application of calcium-phosphate complex liposomes loaded with paclitaxel and miR-124

[0126] 30 nmol of miR-124 was dissolved in 100 μl of DEPC water containing 2M calcium chloride. 150mg PC and 30mg CHOL were dissolved in 1.5ml 5mg / ml PTX in dichloromethane, and the two were mixed and ultrasonically emulsified to obtain colostrum. Dissolve 30mg (mole ratio to PC about 1:50) of mPEG-HA-PC in 15ml of water, add to the above solution for ultrasonic emulsification (2s-2s-60 times, power 200W, ice bath), and vacuum the organic solvent. CaP compounding was carried out according to the ratio of 2ml liposome-36μl 2M calcium chloride solution-450μl 1.6mM sodium phosphate solution.

[0127] The particle diameter of the composite liposome prepared by the present embodiment is as follows: figure 2 shown. The average particle size is 137.8nm, the polydispersity coefficient is 0.179, the encapsulation efficiency of PTX > 95%, the encapsulation efficiency of miR...

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Abstract

The invention relate to a composite nanometer lipid drug delivery system and therapeutic effect thereof on gynecologic tumor, and particularly provides a composite nanometer lipid drug delivery systemincluding (a) taxol as a first active component, (b) targeted inhibitor miRNA as a second active component and (c) a lipid material, with the components (a), (b) and (c) forming composite lipidosomethe average particle size of which is 10-1000 nm. In addition, the system can also include triptolide and curcumin. The system can reduce toxicity of antitumor drugs, enhance antitumor effect, and reduce drug resistance, thus improving patient's compliance.

Description

technical field [0001] The invention belongs to the field of medicine, and more specifically relates to a composite nano-lipid drug delivery system and its preparation method and application, especially in the treatment of gynecological tumors. The drug composite nano lipid drug delivery system of the invention is particularly suitable for preparing drugs for treating gynecological tumors. Background technique [0002] Ovarian cancer is one of the most common gynecological tumors, and its incidence rate ranks third after cervical cancer and uterine body cancer. Ovarian cancer not only has a very high incidence rate, but also has the highest mortality rate among malignant tumors of the female reproductive system, which has seriously affected the health of women and the happiness of countless families; at present, the incidence rate of ovarian cancer in my country is 8.14 / 10 million, the death rate was 3.13 / 100,000. Ovarian cancer is not easy to be diagnosed at an early stage...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/24A61K47/28A61K31/337A61K31/7105A61K48/00A61K45/06A61P35/00
CPCA61K45/06A61K47/24A61K47/28A61K9/127A61K31/337A61K31/7105A61K2300/00
Inventor 李鹤沈鸣茹丹刘欢熊霄源刘蕾付豪段友容
Owner RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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