Pharmaceutical composition, and preparation method and application thereof

A composition and drug technology, applied in the field of medicine, can solve problems such as adverse reactions

Active Publication Date: 2020-09-15
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, direct intravenous administration of chemotherapy drugs and checkpoint antibodies

Method used

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  • Pharmaceutical composition, and preparation method and application thereof
  • Pharmaceutical composition, and preparation method and application thereof
  • Pharmaceutical composition, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Example 1 Preparation of PLG-g-mPEG / DOX nanoparticles (referred to as DOX NPs)

[0075] The molecular weights of polyethylene glycol and polyglutamic acid were respectively selected to be 5000Da and 21600Da, and the drug carrier PLG-g-mPEG was dissolved in dimethyl sulfoxide solution at a concentration of 20 mg / mL. Dissolve commercially available doxorubicin hydrochloride DOX in dimethyl sulfoxide solution at a concentration of 10 mg / mL. Mix the carrier solution and the drug solution according to the corresponding mass ratio of 2:1, then slowly drop the mixed solution into ultrapure water, the volume of ultrapure water used is eight times the volume of dimethyl sulfoxide, and then stir for 20min, stir The mixed solution was placed in a 3500 molecular weight dialysis bag and dialyzed for 2 days to prepare PLG-g-mPEG / DOX nanoparticles. The particle size of the prepared nanoparticles is 100 nm. The drug loading capacity is 28.6%, and the drug loading rate is 80.3%. The ...

Embodiment 2

[0078] Example 2 Preparation of PEG / PLG / PEI / Spam1+shPD-L1 (Spam1+shPD-L1NPs for short)

[0079] The molecular weights of polyethyleneimine and polyglutamic acid were respectively selected as 25KDa and 2000Da, PEI was dissolved in the aqueous solution at a concentration of 5mg / mL, and polyglutamic acid was dissolved in the aqueous solution at a concentration of 1mg / mL. The two are mixed according to the mass ratio PEI:PLG=5:1. Vortex to mix well, compound for 15 minutes to form PEI / PLG nanoparticles. Mix the Spam1 plasmid and the shPD-L1 plasmid in equal amounts to form an aqueous solution, and the plasmid concentration is 1 mg / mL respectively. Mix the plasmid mixed solution with the PEG / PLG nanoparticle solution, vortex and mix well, and compound for 15 minutes. Dialdehyde PEG was dissolved in water at a concentration of 10 mg / mL. And add it to the previous plasmid nanoparticles, vortex and mix well, and compound for 15 minutes. The final mass ratio of each substance is: P...

Embodiment 3

[0080] Example 3 Anti-tumor therapy of DOX NPs combined with Spam1+shPD-L1NPs

[0081] C57BL6 mice aged 4-6 weeks were randomly divided into 8 groups, 6 mice in each group. One million B16F10 cells were injected subcutaneously to construct a subcutaneous tumor model. Each group of mice received different treatments, and the experimental scheme was as follows: figure 1 As shown in a:

[0082] The mice in the PBS group were used as a control, and were only given the same amount of PBS buffer;

[0083] The dose of DOX NPs group was 5mg / kg;

[0084] The dose of shPD-L1NPs group was 0.75mg / kg;

[0085] DOX NPs+shPD-L1Nps group, according to figure 1 As shown in middle a, 5 mg / kg of DOX NPs and 0.75 mg / kg of shPD-L1NPs were administered;

[0086] The dosage of Spam1 NPs group was 0.75mg / kg;

[0087] DOX NPs+Spam1NPs group, according to figure 1 As shown in a, 5mg / kg of DOXNPs and 0.75mg / kg of Spam1NPs were given;

[0088] (shPD-L1+Spam1)NPs group, according to figure 1 As sh...

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Abstract

The invention relates to the technical field of medicines, and in particular relates to a pharmaceutical composition, and a preparation method and application thereof. The pharmaceutical composition provided by the invention comprises at least two selected from a group consisting of a substance for triggering tumour cell immunogenic death, an immune checkpoint inhibitor and a substance for degrading extracellular matrix in a tumour area; components are supported by a carrier, and can specifically release drugs in a tumour acidic microenvironment to trigger tumour cell death; and thus, the purpose of treating cancers is achieved. Researches show that combined use of the three components can improve the tumour inhibition effect; and the effect is better than that of the three components which are used independently, or combined use of the two.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a pharmaceutical composition and its preparation method and application. Background technique [0002] Cancer immunotherapy, surgery, chemotherapy and radiotherapy have become the first-line therapies against cancer in clinic. Unlike other therapies that target cancer cells, cancer immunotherapy aims to normalize the body's immune system that fights cancer, rather than targeting the tumor directly. Immune checkpoint blockade (ICB) is a classic approach in cancer immunotherapy. ICBs, which interfere with the interaction between immune checkpoints and their receptors, have had encouraging therapeutic effects in many cancer types. However, the low response rate of ICB largely limits its further development. Previous findings have shown that improving the quality of tumor antigens and promoting immune cell infiltration will greatly enhance the therapeutic effect of ICB. [0003]...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K47/64A61K47/60A61K47/59A61K47/69A61K31/704A61K48/00A61P35/00
CPCA61K31/704A61K45/06A61K48/0041A61K48/005A61K47/59A61K47/60A61K47/64A61K47/6935A61P35/00A61K2300/00
Inventor 田华雨吴嘉言陈杰郭兆培林琳孙平杰徐彩娜陈学思
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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