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Pharmaceutical composition containing IL-15 cationic liposome compound and celecoxib liposome as well as preparation method and application of pharmaceutical composition

A technology of cationic liposome and celecoxib, which is applied in the field of medicine to achieve the effects of improving tumor targeting, reducing tumor immunosuppression, and avoiding the damage of pH environment

Pending Publication Date: 2021-11-26
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] From the above analysis, it can be seen that IL-15, celecoxib and cationic liposome non-viral carrier system have their own characteristics and defects in the treatment of tumors. It seems that the combination of them can produce greater anti-tumor effects. benefit, but unfortunately, there is no teaching in the prior art to combine celecoxib liposome and IL-15 cationic liposome complex for NK immune activation, let alone use the two in combination to treat tumors

Method used

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  • Pharmaceutical composition containing IL-15 cationic liposome compound and celecoxib liposome as well as preparation method and application of pharmaceutical composition
  • Pharmaceutical composition containing IL-15 cationic liposome compound and celecoxib liposome as well as preparation method and application of pharmaceutical composition
  • Pharmaceutical composition containing IL-15 cationic liposome compound and celecoxib liposome as well as preparation method and application of pharmaceutical composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0075] Embodiment 1: Preparation of celecoxib liposome

[0076]Accurately weigh 64 mg of soybean lecithin, 4 mg of celecoxib, and 8 mg of cholesterol, respectively, and place them in a 25 mL round-bottomed flask, add a mixed solution of chloroform and methanol (V:V=1:1) and oscillate until completely dissolved, and evaporate in a vacuum at 37°C. After all the films were formed, add Hepes buffer, hydrate in a water bath at 60°C for 10 minutes, sonicate with a probe ultrasonic cell disruptor (200W, 3 minutes) and pass through a 0.22 μm microporous membrane to obtain celecoxib liposomes.

Embodiment 2

[0077] Embodiment 2: the mensuration of celecoxib liposome encapsulation efficiency

[0078] Select the ultraviolet absorption wavelength 252nm to detect celecoxib. The absorption intensity value A of celecoxib with different concentrations of 5, 10, 20, 50, and 100 μg / mL was measured at this wavelength, and the standard curve was drawn with the ultraviolet absorption intensity A as the ordinate and the concentration C as the abscissa. The standard curve of CEL is A=0.0242C-0.0172, R 2 = 0.9909. The results showed that CEL had a good linear relationship in the range of 5-100μg / mL.

[0079] Precisely draw the celecoxib liposome solution after ultracentrifugation, put it in a 10mL volumetric flask, then add methanol to carry out ultrasonic demulsification, measure its ultraviolet absorption intensity A with a UV spectrophotometer, and then in different drug-to-lipid ratios: Under the conditions of 1:5, 1:10, 1:15, and 1:20, the encapsulation efficiency was measured according ...

Embodiment 3

[0083] Embodiment 3: Characterization of celecoxib liposome formulation

[0084] (1) Morphological observation: Take 9 μL of celecoxib liposomes prepared in Example 1 and slowly drip it onto the center of the copper mesh covered with carbon film, let it stand for 1 minute, then use filter paper to suck off the excess liquid, and absorb 9 μL of phosphotungstic acid ( 2%) negative staining for 1 minute, use the above operation to absorb excess liquid, put it into a transmission electron microscope for detection and take pictures, as figure 1 shown. Depend on figure 1 It can be observed that the shape of the complex is regular, the shape is spherical, and the distribution is uniform, and the particle size of the liposome is about 120nm.

[0085] (2) Determination of particle size and potential: We used a Malvern laser particle size analyzer to characterize liposome Zeta potential. Take liposome solutions with different concentrations and carefully add them into the potentiomet...

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Abstract

The invention belongs to the field of medicines, and particularly relates to a pharmaceutical composition containing an IL-15 cationic liposome compound and a celecoxib liposome as well as a preparation method and application of the pharmaceutical composition. In the pharmaceutical composition, the IL-15 cationic liposome compound is a delivery system of a folic acid PEGylation DOTAP cationic liposome nuclear transport gene drug, which is designed by taking plasmid DNA (pcDNA3.1 / IL-15) capable of editing and releasing a cell factor IL-15 as a gene drug, after the IL-15 cationic liposome compound and Celecoxib liposome which is released in a targeted manner in TIME are used in a combined manner, Celecoxib promotes NK-cells to be recruited into a tumor microenvironment, infiltration of the NK-cells is greatly improved, IL-15 factors promote proliferation and activation of the NK-cells in the tumor microenvironment, the number of Treg cells is remarkably reduced, the tumor microenvironment is changed, the immunosuppression is relieved to a certain degree, the two components are combined for use, so that the inherent immune anti-tumor effect can be better played, and the safe and low-toxicity synergistic tumor immunotherapy effect is played.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a pharmaceutical composition comprising IL-15 cationic liposome complex and celecoxib liposome, a preparation method and application thereof. Background technique [0002] Tumor immunotherapy is a new tumor treatment strategy after surgery, radiotherapy and chemotherapy. Among them, NK-cell-based immunotherapy technology has received more and more attention. The role of NK-cells is to recognize and dissolve tumor cells and virus-infected cells, and to produce two main functions of immunoregulatory cytokines. They are important immune regulatory cells for the human body to resist infection, prevent autophagy and prevent cell malignant differentiation. The number and activity of NK-cells in the peripheral blood of tumor patients are significantly reduced. If the proliferation and activation of NK-cells can be promoted to produce more cells to kill tumor cells, the ant...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K9/127A61K31/635A61K38/20A61K47/24A61K47/28A61K47/54A61K47/60A61K47/69A61P35/00
CPCA61K48/0008A61K48/005A61K38/2086A61K31/635A61K47/545A61K47/60A61K47/6911A61K9/1277A61K47/24A61K47/28A61P35/00A61K2300/00Y02A50/30
Inventor 江芷萱宋宝慧常爽胡海洋陈大为
Owner SHENYANG PHARMA UNIVERSITY
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