Cyclooxygenase-2 inhibitor and nano-drug delivery system drug composition and application thereof

A technology of nano-medicine and cyclooxygenase, which is applied in the direction of drug combination, capsule delivery, anti-tumor drugs, etc., to improve the therapeutic effect, promote normalization, and reduce the effect of tumor stromal cells

Inactive Publication Date: 2017-12-08
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, there is currently no research on the application of COX-2 inhibitors to comprehensi

Method used

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  • Cyclooxygenase-2 inhibitor and nano-drug delivery system drug composition and application thereof
  • Cyclooxygenase-2 inhibitor and nano-drug delivery system drug composition and application thereof
  • Cyclooxygenase-2 inhibitor and nano-drug delivery system drug composition and application thereof

Examples

Experimental program
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Effect test

Example Embodiment

[0031] Example 1. The comprehensive regulation effect of celecoxib on tumor microenvironment

[0032] A549 lung cancer model mice were treated with celecoxib for two consecutive weeks (a dose of 200mg / kg / d), then sacrificed, cardiac perfused, and tumors were taken to prepare frozen sections; immunofluorescence staining, FAPα antibody labeled TAF (green ), fibronectin is used as a representative extracellular matrix, labeled with fibronectin (green), pericytes are labeled with SMA-α antibody (green), and vascular endothelial cells are labeled with CD-31 antibody (red). The experimental results show that, Compared with the control group, the fibroblasts in the celecoxib group were significantly reduced (such as figure 2 Shown in A, P figure 2 B), the coverage rate of pericytes to endothelial cells increased significantly (such as figure 2 Shown in C, P 488 labeled lectin ( 488-lectin), the dose was 5mg / kg, and the animals were killed by carbon dioxide asphyxiation after 1 hour....

Example Embodiment

[0033] Example 2. The effect of celecoxib on the delivery of micellar tumors after regulating the tumor microenvironment

[0034] Weigh mPEG 2000 -PLA 2000 20mg, dissolved in 1ml of acetonitrile, ultrasonically dispersed, 40°C rotary evaporation for 2h to remove acetonitrile, reconstituted with PBS preheated at 40°C for several minutes to obtain a blank micelle preparation; use a particle size / Zeta potential analyzer to measure the blank micelle The average particle size and Zeta potential value, the measured micelle particle size is about 22.1±1.5nm (such as image 3 A), the potential is -3.1±0.7mv. After the micelles were negatively stained with 2% (w / v, pH=7.0) phosphotungstic acid, the morphology of the micelles was observed by transmission electron microscope. The results showed that the particles under the electron microscope were spherical, regular in shape, smooth surface, and good dispersion (such as image 3 Shown in B);

[0035] After administration of celecoxib to the ...

Example Embodiment

[0037] Example 3 The therapeutic effect of celecoxib combined with paclitaxel-loaded micelles on A549 tumor

[0038] When the tumor diameter reached 4-5mm, 24 tumor-bearing nude mice models were randomly divided into four groups, each with 6 mice. a, Control group (two weeks of blank celecoxib preparation by gavage, after the treatment is finished, blank micelles are given to the tail vein); b, Celecoxib group (two weeks of celecoxib preparation is given by gavage, and the tail vein is given after treatment Blank micelles); c, Control+Micelles-PTX group (two-week blank celecoxib preparation was treated by gavage, and paclitaxel-loaded micelles were given to the tail vein after the treatment); d, Celecoxib++Micelles-PTX group (two weeks Celecoxib preparations were treated by intragastric administration. After the treatment, paclitaxel-loaded micelles were administered to the tail vein); the administration method of paclitaxel micelles or blank micelles was: the start of tail vein ...

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Abstract

The invention belongs to the technical field of biology and relates to a tumor targeting therapy drug composition, in particular to a cyclooxygenase-2 inhibitor and nano-drug delivery system drug composition and application thereof. According to the drug composition, COX-2 serves as a target spot to comprehensively adjust and control the tumor microenvironment so as to increase nano-drug tumor-interior delivery to be used for tumor therapy. By inhibiting COX-2 of the tumor position, reducing tumor matrix cells, destroying tumor matrix components, facilitating normalization of tumor blood vessels and increasing tumor-interior blood flow pouring and nano-particle tumor-interior penetration, tumor-interior delivery of nano drugs is increased, and the therapy effect of the nano drugs for tumor is improved. The invention provides a novel intervention strategy aiming at the tumor for clinical practice.

Description

technical field [0001] The invention belongs to the field of biological technology, and relates to a pharmaceutical composition for targeted tumor therapy, in particular to a pharmaceutical composition of a cyclooxygenase-2 inhibitor and a nanometer drug delivery system and its application. Enzyme-2 as a target to regulate the tumor microenvironment to increase the intratumoral delivery of nanomedicine for the treatment of solid tumors. Background technique [0002] The prior art discloses that the tumor microenvironment includes extracellular matrix and stromal cells, such as tumor-associated fibroblasts, vascular endothelial cells, macrophages, pericytes, and some immune cells and adipocytes. The tumor microenvironment makes the internal environment of the tumor very complicated, which seriously affects the drug delivery of the tumor. The impact mainly includes: ① Leakage of blood vessels inside the tumor, poor function, coupled with the extrusion of the matrix, the blood ...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/635A61K31/337A61K9/107A61K9/51A61P35/00
Inventor 庞志清张波蒋新国沈顺
Owner FUDAN UNIV
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