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Anti-tumor drug prepared from combination of deoxyadenosine with other nucleosides or bases and preparation method and application thereof

A deoxypurine nucleoside and anti-tumor drug technology, applied in the field of new tumor drug development, to achieve the effects of obvious anti-tumor effect, delaying tumor drug resistance and remarkable therapeutic effect

Inactive Publication Date: 2016-11-09
张始状
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the combination of normal deoxypurine nucleosides with other nucleosides or bases to prepare anti-tumor drugs has not been reported at home and abroad.

Method used

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  • Anti-tumor drug prepared from combination of deoxyadenosine with other nucleosides or bases and preparation method and application thereof
  • Anti-tumor drug prepared from combination of deoxyadenosine with other nucleosides or bases and preparation method and application thereof
  • Anti-tumor drug prepared from combination of deoxyadenosine with other nucleosides or bases and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0095] The 245 combination, 25 combination, 2145 combination tumor suppression experiment, the specific experimental methods are as follows:

[0096] 1. Inoculation of cells

[0097] Take Hela cells and 7402 cells in the logarithmic growth phase, digest with trypsin and dilute to (2.0~3.0)×104 / mL viable cell suspension, inoculate 2~10 rows in 96-well culture plate, each row Set up 6 replicate wells, each with 100μL, add 100μL of RPMI-1640 culture medium containing 10% fetal bovine serum to the 11th column, fill with 100μL PBS around, place at 37℃, 5%CO 2 Cultivate for 24h in an incubator.

[0098] 2. Dosing intervention

[0099] After the cells adhere to the wall, discard the culture medium in the well, and add 245 combinations in order from large to small. The molar ratio of 2, 4, and 5 is 2:1:2. The seven concentration gradients of the combined drugs (C1~C7 ), the total concentrations are 2.0 mmol / L, 1.0 mmol / L, 0.5 mmol / L, 0.25 mmol / L, 0.125 mmol / L, 0.0625 mmol / L, 0.03125 mmol / L; ...

Embodiment 2

[0120] The factorial design experiment of any three nucleoside combinations in vitro anti-tumor, the specific experimental methods are as follows:

[0121] 1. Inoculation of cells

[0122] See the "cell seeding" step in Example 1

[0123] 2. Dosing intervention

[0124] After the cells adhere to the wall, discard the culture medium in the well, and add 1 (adenosine), 2 (deoxyadenosine), 3 (adenine), 4 (guanosine), 5 (deoxyguanosine), 6 (guanine) six drugs and a combination of these six drugs with a molar ratio of 1:1:1 (123, 124, 125, 126, 134, 135, 136, 145, 146, 156) , 234, 235, 236, 245, 246, 256, 345, 346, 356, 456);

[0125] Use RPMI-1640 culture medium containing 10% fetal bovine serum to dispense to the required concentration, add 200 µL to each well;

[0126] The blank control group and the negative control group were respectively added with 200 µL of RPMI-1640 culture medium containing 10% fetal bovine serum and placed at 37°C, 5% CO 2 In an incubator.

[0127] 3. Color

[0128]...

Embodiment 3

[0145] Orthogonal experimental design of deoxyadenosine-guanosine-deoxyguanosine (245) combination concentration ratio, the specific experimental steps are as follows:

[0146] 1. Inoculation of cells

[0147] Take Hela cells and 7402 cells in the logarithmic growth phase, digest with trypsin and dilute to (2.0~3.0)×104 / mL viable cell suspension, inoculate 2~10 rows in 96-well culture plate, each row Set up 6 replicate wells, each with 100μL, add 100μL of RPMI-1640 culture medium containing 10% fetal bovine serum to the 11th column, fill with 100μL PBS around, place at 37℃, 5%CO 2 Cultivate for 24h in an incubator.

[0148] 2. Dosing intervention

[0149] After the cells adhere to the wall, discard the culture medium in the well, and the dosing scheme is as follows: the concentration of 2 (deoxyadenosine), 4 (guanosine), and 5 (deoxyguanosine) are all 3mmol / L, and the 9 groups designed are respectively : The molar ratios of 2 (deoxyadenosine), 4 (guanosine), and 5 (deoxyguanosine) ar...

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Abstract

The invention discloses an anti-tumor drug prepared from combination of deoxyadenosine with other nucleosides or bases and a preparation method and application thereof. The deoxyadenosine includes deoxyadenosine and deoxyguanosine; the other nucleotides and bases include: deoxycytidine, thymidine, adenosine, guanosine, cytidine, uridine, adenine, guanine, cytosine, uracil and thymidine; The invention has the advantages that both the deoxyadenosine and other nucleosides or bases are human normal nucleotides, the drug for treating various common malignancies such as gastric cancer, lung cancer, liver cancer, colon cancer, esophageal cancer, pancreatic cancer, breast cancer and genital system neoplasms is prepared from the combination of deoxyadenosine as a main drug and other nucleotides and bases as auxiliaries, and the drug has features wide spectrum, low toxicity, mechanism novelty and the like in terms of anti-tumor action; the combine drug has lower toxic and side effects than a single drug; anti-tumour effects are more multiplicative; meanwhile drug resistance of tumors can be delayed.

Description

[0001] The present invention is a divisional application of application number 201410675196.4, application date: November 24, 2014, and title of the invention: "antineoplastic drugs prepared by combining deoxypurine nucleosides and other nucleosides or bases and their preparation methods and applications". Technical field [0002] The present invention relates to the application of the combination of human normal deoxyadenosine nucleosides and nucleosides or bases in the preparation of tumor drugs, specifically combining one or two of deoxyadenosine and deoxyguanosine with nucleosides or bases One or more of the combined drugs are used to treat tumors. The most classic one is to combine two deoxypurine nucleosides and one other nucleoside or base to prepare tumor drugs. It belongs to the field of new tumor drug development. Background technique [0003] Nucleoside (nucleoside) is formed by the connection of base and five-carbon sugar (ribose or deoxyribose), that is, N-9 of purin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/708A61K31/7076A61K9/107A61K9/20A61K47/44A61P35/00
CPCA61K47/44A61K9/0019A61K9/107A61K9/2059A61K31/7076A61K31/708A61K2300/00
Inventor 张始状
Owner 张始状
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