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Antineoplastic medicament and adenovirus composite preparations and uses thereof

A technology of anti-tumor drugs and compound preparations, applied in the field of biomedicine, can solve problems such as lack of targeting, achieve the effects of increasing toxic and side effects, enhancing efficacy, and improving cure rate

Inactive Publication Date: 2008-03-12
上海交通大学附属第一人民医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

② Lack of targeting
There are also studies that suggest that adenovirus can sensitize antitumor drugs, but so far, there has been no research on antitumor drugs that increase the expression level of adenovirus-mediated exogenous genes in tumor cells, prolong the duration of gene expression, and in tumor cells. Reports on the use of small doses of antineoplastic drugs as adjuvants in gene therapy to increase the level and time of gene expression mediated by adenovirus

Method used

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  • Antineoplastic medicament and adenovirus composite preparations and uses thereof
  • Antineoplastic medicament and adenovirus composite preparations and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1 The antitumor drug doxorubicin increases the gene expression level of Ad5-GFP in various tumor cells

[0053] According to the different doses of Ad5-GFP combined with doxorubicin, the experiment was divided into 10 groups. Doxorubicin doses were 0.1 μg / ml (0.1 μg), 1.3 μg / ml (1.3 μg), 1.7 μg / ml (1.7 μg), 10 μg / ml (10 μg), 20 μg / ml (20 μg), 30 μg / ml ml (30 μg), 40 μg / ml (40 μg), 60 μg / ml (60 μg) and 80 μg / ml (80 μg), the last group was Ad5-GFP alone. The dosage of Ad5-GFP was 10moi (the total amount was 1×10e6).

[0054] The tumor cells involved in the experiment include human non-small cell lung cancer cell line NCI-H446, human small cell lung cancer cell line NCI-H460, human lung adenocarcinoma cell line A549, human liver cancer cell line SMMC-7721, human gastric cancer cell line SGC7901, Human breast cancer cell line SKBR-3, human ovarian cancer cell line SKOV-3 and mouse bladder transitional epithelial cancer cell line BTT.

[0055]The above-mentioned v...

Embodiment 2

[0061] Example 2 The antitumor drug cytarabine increases the gene expression level of Ad5-GFP in various tumor cells

[0062] According to the dose of cytarabine combined with Ad5-GFP, the experiment was divided into 7 groups. The combined doses of cytarabine are 0.1 μg / ml (0.1 μg), 1 μg / ml (1 μg), 10 μg / ml (10 μg), 20 μg / ml (20 μg), 40 μg / ml (40 μg) and 60 μg / ml (60 μg), and the last group was Ad5-GFP alone. The dosage of Ad5-GFP was 10moi (the total amount was 1×10e6 PFU).

[0063] The tumor cells involved in the experiment include human non-small cell lung cancer cell line NCI-H446, human small cell lung cancer cell line NCI-H460, human lung adenocarcinoma cell line A549, human liver cancer cell line SMMC-7721, human gastric cancer cell line SGC7901, Human breast cancer cell line SKBR-3, human ovarian cancer cell line SKOV-3 and mouse bladder transitional epithelial cancer cell line BTT.

[0064] The above-mentioned various cells were inoculated in 24-well cell culture p...

Embodiment 3

[0070] Example 3 The antineoplastic drug etoposide increases the gene expression level of Ad5-GFP in various tumor cells

[0071] According to the dose of etoposide combined with Ad5-GFP, the experiment was divided into 7 groups. The dose of etoposide used in combination is 20 μg / ml (20 μg), 40 μg / ml (40 μg), 60 μg / ml (60 μg), 80 μg / ml (80 μg), 100 μg / ml (100 μg), 200 μg / ml (200 μg), The last group is the application of Ad5-GFP alone. The dosage of Ad5-GFP was 10moi (1×10e6 PFU in total).

[0072] The tumor cells involved in the experiment include human non-small cell lung cancer cell line NCI-H446, human small cell lung cancer cell line NCI-H460, human lung adenocarcinoma cell line A549, human liver cancer cell line SMMC-7721, human gastric cancer cell line SGC7901, Human breast cancer cell line SKBR-3, human ovarian cancer cell line SKOV-3 and mouse bladder transitional epithelial cancer cell line BTT.

[0073] The above-mentioned cells were seeded in 24-well cell culture...

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Abstract

The present invention belongs to the biological field and the medical field, which relates to an adenovirus composite preparation for a new genetic therapy as well as the application and the application method. The present invention demonstrates that when the adenovirus is taken as a gene delivery vector, the combined use of adenovirus with a certain dose of antitumor drug can dramatically enhance the foreign gene expression of the adenovirus and significantly prolong the period of the foreign gene expression, and the therapy effect of the gene is improved. The composite preparation and the application method of the present invention can be applied as a guide of the genetic therapy of the malignant tumor, the eye disease, the genetic disease, the cardiovascular disease and the neuromuscular disorder, etc.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to a new compound preparation for gene therapy, in particular to the compound preparation composed of antitumor drugs and adenovirus and its application and application method. Background technique [0002] Malignant tumors are major diseases that seriously threaten human health. Malignant tumors have become the second cause of death worldwide. Although great progress has been made in the treatment of malignant tumors, the remission and cure rates still cannot be changed for advanced tumors. The implementation and completion of the Human Genome Project has provided a huge resource pool for the development of new drugs, and has also greatly changed the thinking of clinical diagnosis, prevention and treatment of diseases. Since the first gene therapy program was approved for clinical trials in the United States in 1990, gene therapy has been developing steadily. According to incomplete stati...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K45/00A61K31/7052A61K31/4745A61K31/7048A61K31/282A61K33/24A61P35/00
Inventor 黄倩吴继红张圣海刘新建吴小兵董小岩韦芳陈霞芳田毓华谢匡成李川源
Owner 上海交通大学附属第一人民医院
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