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Antineoplastic medicine preparation and prepn. method therefor

A composition and anti-tumor technology, which is applied in the direction of drug combination, bacteria, nervous system diseases, etc., can solve the problems of non-specific anti-tumor effect, neurotoxicity and allergic reaction, and limit anti-tumor effect, so as to achieve easy purchase and high cost. curative effect, less damage effect

Inactive Publication Date: 2011-07-06
BIOMEDICAL ANALYSIS CENT OF ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, cisplatin is highly toxic to the human body, and patients will experience various side effects when applied in large doses, such as gastrointestinal reactions, nephrotoxicity, neurotoxicity, and allergic reactions, which limit its anti-tumor effect to a certain extent.
If cisplatin is injected intravenously, the drug will be distributed throughout the body and metabolized quickly, and cannot specifically reach the tumor site to exert its anti-tumor effect, and cannot accumulate a high concentration in the tumor site, and the anti-tumor effect is non-specific
At present, there is no report on the use of Escherichia coli's ability to target tumors and accumulate heavy metals to exert anti-tumor effects

Method used

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  • Antineoplastic medicine preparation and prepn. method therefor
  • Antineoplastic medicine preparation and prepn. method therefor
  • Antineoplastic medicine preparation and prepn. method therefor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1 Establishment of Recipient Animals and Tumor Models

[0037] 1. Materials and methods

[0038] 1.1 Bacteria, cells and their culture conditions

[0039] Escherichia coli DH5α, BL21 and HB101 were stably integrated with fluorescent plasmid pXen-1, which were all purchased from Xenogen. Plasmid pXen-1 is resistant to ampicillin, and the bacteria can grow in the medium with ampicillin without adding additional substances. In the experiment of observing the growth inhibition of simple Escherichia coli on tumors, Escherichia coli was cultured in a culture medium with ampicillin at 37°C and 220 rpm for 6-8 hours until the OD600 reached 0.6-0.8. Bacillus growth reached mid-log phase. Bacteria were harvested, washed 3 times with sterile normal saline, centrifuged to precipitate, and finally resuspended with a certain volume of normal saline. The cisplatin used was purchased from the 307 Hospital of the Chinese People's Liberation Army. The cells used were B16 mela...

Embodiment 2

[0045] Example 2 Detection of Escherichia coli enrichment of cisplatin by ICP-MS

[0046] 1. Material: same as embodiment one.

[0047] 2. Method results:

[0048] Shake Escherichia coli DH5α in 5ml LB medium with ampicillin to 0.6-0.8, add 0.5mg, 0.25mg, 0.05mg of cisplatin respectively, and incubate for 1h, 12h, 48h for long-term culture. The Escherichia coli treated with cisplatin were washed five times with 1×PBS, centrifuged, placed in an oven at 60°C for 24 hours, after being thoroughly dried, weighed, and sent to ICP-MS for detection of platinum content. Long-term culture means that the bacteria are transferred to LB medium containing a certain concentration of cisplatin, placed in a shaker, 37°C, 220 rpm, and cultured until the OD of the bacteria reaches about 1.5. It was found that the amount of platinum enriched by Escherichia coli increased with the concentration of cisplatin, and the Escherichia coli absorbed the largest amount of cisplatin after incubation for 2...

Embodiment 3

[0049] Example 3 Observation of the Inhibitory Effect of Simple Bacteria on Tumor Growth

[0050] 1. Materials:

[0051] Same as embodiment one.

[0052] 2. Method results:

[0053] Set up experimental group 1, experimental group 2, and control group. Five mice in each of the experimental group and the control group, Balb / C mice, male, 6-8 weeks old, were purchased from the Experimental Animal Center of the Academy of Military Medical Sciences. Shake the Escherichia coli DH5α transformed with pXen-1 to 0.6-0.8 in the medium with ampicillin, collect the bacteria in the middle logarithmic growth phase, wash with sterile normal saline for 3 times, centrifuge, and reconstitute with a certain volume of normal saline. overhang, the 1 x 10 8 cfu / 100 μl of Escherichia coli was injected into the tumor-bearing mice of the experimental group through the tail vein, and the tumor inoculated into the mice was B16 melanoma, and the injection time was 7 days after the inoculation of the tum...

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Abstract

An antineoplastic composite medicine features that the living colibacillus rich in antineoplastic substance (cisplatin) is one of its active components. After the living colibacillus carries the cisplatin to the tumor position, it can specifically play its antineoplastic role.

Description

technical field [0001] The invention relates to an anti-tumor pharmaceutical composition, and also relates to a preparation method of the pharmaceutical composition. Background technique [0002] Some live bacteria have been found to accumulate in tumor tissues for about 150 years, and the purposeful use of this characteristic of these bacteria in the study of tumor therapy began in the middle of the last century. Three bacteria have been studied most intensively in this regard: Salmonella, anaerobic bacillus and bifidobacteria. Among them, anaerobic bacillus and bifidobacteria mainly reproduce in tumor necrosis sites, and their affinity for tumors depends on the size of tumor volume [Dang LH, Beltegowda C, Huso DL, et al. Combinationbacteriolytic therapy for the treatment of experimental tumors. PNAS 2001;98:15155-60]. Salmonella is a facultative anaerobic bacterium that can grow in both tumor necrosis and living tumor tissue, and its tumor affinity does not depend on tum...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K35/74A61P25/00C12N1/21
Inventor 张学敏王晨辉张海英
Owner BIOMEDICAL ANALYSIS CENT OF ACADEMY OF MILITARY MEDICAL SCI