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Composition and pharmaceutical preparation and application thereof

A technology for pharmaceutical preparations and compositions, which is applied to compositions and pharmaceutical preparations and their application fields, can solve problems such as ineffective treatment and docetaxel resistance, reduce toxic side effects, improve drug sensitivity, and enhance inhibitory activity. Effect

Inactive Publication Date: 2017-06-13
GUANGDONG UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Docetaxel is a very effective anti-tumor chemotherapy drug. However, with the increase of drug time and dosage, patients are prone to develop resistance to docetaxel, which often leads to ineffective treatment and death

Method used

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  • Composition and pharmaceutical preparation and application thereof
  • Composition and pharmaceutical preparation and application thereof
  • Composition and pharmaceutical preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] The cell viability of prostate cancer cells was measured by CCK-8 assay, and the specific process was as follows:

[0037] 1. Obtain test cells: human prostate cancer cell lines LNCaP and PC-3.

[0038] 2. Prepare different ratios of docetaxel and YK-4-279 compositions respectively, the molar concentrations of docetaxel and YK-4-279 in the composition are set to 1:100, 1:500 and 1:100 respectively : 1000, and set up 1 group of blank control and 4 groups of positive control. Wherein, the concentration of the docetaxel group in the positive control group was set to 1 nM, and the concentrations of the YK-4-279 group were set to 0.1 μM, 0.5 μM and 1 μM, respectively.

[0039] 3. Divide the test cells into 2×10 4 cells / ml inoculated in a 96-well plate, add 100ul of cell suspension to each well, culture in a cell culture incubator for 24h, then add the sample solution prepared in step 2 for 72h, remove the old medium and add new Add 10 ul of CCK-8 reagent to each well of t...

Embodiment 2

[0042] The number of living cells of prostate cancer cells LNCaP and PC-3 was measured when docetaxel and YK-4-279 were administered in combination at a molar concentration of 1:1000 by trypan blue exclusion test, and the specific embodiments were as follows:

[0043] Divide LNCaP and PC-3 cells into 2 × 10 4 cells / ml inoculated in a petri dish with a diameter of 35 mm, add 2 ml of cell suspension to each dish, culture in a cell incubator for 24 hours, then treat with the test sample for 72 hours, digest with trypsin and prepare a single cell suspension liquid. Take 80ul of cell suspension and mix with 20ul of 0.4% trypan blue solution, stain for 5min, count with a hemocytometer under an inverted microscope, the cells stained blue are dead cells, otherwise they are live cells. Among them, the concentration of the test sample docetaxel (nM)-YK-4-279 (μM) was set to 4 gradients of 0.1, 0.5, 1, and 2, and the same concentration of docetaxel was used alone Or YK-4-279 as a posit...

Embodiment 3

[0047] The effects of 0.5nM docetaxel and 0.5uM YK-4-279 alone and in combination on the apoptosis of human prostate cancer cells LNCaP and PC-3 were studied. The number of dead cells was measured by trypan blue exclusion test, and apoptosis was studied by combining propidium iodide staining with morphological evaluation. The specific implementation scheme is as follows:

[0048] Divide LNCaP and PC-3 cells into 2 × 10 4 cells / ml inoculated in a petri dish with a diameter of 35mm, added 2ml of cell suspension to each dish, placed in a cell culture incubator for 24h, and then treated with 0.5nM docetaxel and 0.5uM YK-4-279 alone or in combination Treat for 72 hours, digest with trypsin and prepare a single cell suspension, then use a smear centrifuge to prepare a single cell layer smear, and fix with a fixative solution (acetone:methanol=1:1) for 10 minutes at room temperature. Stain with PI (1ug / ml in PBS) staining solution for 10 min, and randomly select a field of view to t...

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Abstract

The invention relates to a composition and pharmaceutical preparation and application thereof. The composition and pharmaceutical preparation comprises docetaxel and YK-4-279, the molar concentration ratio of which is 1:1000, the compounding is reasonable, the combination of the two not only can improve the pharmaceutical sensitivity of docetaxel, but also realizes the effects of the YK-4-279 in aspects of anti-prostate cancer as an ETV1 small-molecular inhibitor, and the treatment effect of docetaxel can be synergistically enhanced. Experiments proved that the combination of docetaxel and YK-4-279 has obviously enhanced inhibition activity to human prostate cancer cells compared with single medication, furthermore, the administration dose in cancer treatment can be decreased, the toxic and side effects of the medicines can be reduced, the harm to a human body can be decreased, and the composition and pharmaceutical preparation hopefully becomes a high-efficiency and low-toxicity anti-prostate cancer drug.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to a composition, a pharmaceutical preparation and applications thereof. Background technique [0002] Prostate cancer refers to epithelial malignant tumors that occur in the prostate. According to the pathological type, it includes adenocarcinoma, ductal adenocarcinoma, urothelial carcinoma, squamous cell carcinoma, and adenosquamous carcinoma. Among them, prostate adenocarcinoma accounts for more than 95%. Therefore, usually When we say prostate cancer we mean prostate adenocarcinoma. Prostate cancer is one of the most frequent cancers in European and American men, and it is the second most lethal cancer among male cancer patients. With the changes in the environment and diet, in recent years, in Asia, the number of prostate cancer patients has also shown a clear upward trend. [0003] The most commonly used treatment for metastatic androgen-sensitive prostate cancer...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/404A61K31/337A61P35/00
CPCA61K31/404A61K31/337A61K2300/00
Inventor 喻琳郑希吴晓凤黄华容何燕杜志云张焜
Owner GUANGDONG UNIV OF TECH
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