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Radiation sensitizer used for brain tumor

A technology of radiation and sensitizers, applied in the field of radiation sensitizers, can solve problems such as undeveloped medicines, and achieve the effect of improving the effect

Active Publication Date: 2014-05-28
POLA PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In other words, in brain tumors, radiation therapy alone cannot be said to be sufficient, and the development of auxiliary means such as radiosensitizers is expected, but it can be said that drugs that sufficiently exert such effects have not yet been developed

Method used

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  • Radiation sensitizer used for brain tumor
  • Radiation sensitizer used for brain tumor
  • Radiation sensitizer used for brain tumor

Examples

Experimental program
Comparison scheme
Effect test

manufacture example

[0029] The radiation sensitizer of the present invention is made according to the following Tables 1 and 2. That is, the formulation components are heated, melted, sterilized and filtered, and returned to room temperature to prepare an injection.

[0030] Table 1

[0031]

[0032] Table 2

[0033]

[0034] These radiation sensitizers were left at 20°C. As a result, no crystals were precipitated until 5 hours, and crystals were observed after 22 hours. The degree of radiation sensitizer 4>radiation sensitizer 1> The order of radiation sensitizer 2>radiation sensitizer 3. Thus, addition of creatinine was judged to increase solubility. In view of the metabolic rate of doradazole, such an effect is beneficial to improve the pharmacokinetic properties.

Embodiment 1

[0038]

[0039] Male 11-week-old Fisher344 rats (Fisher344) were used as animals, and 1×10 6 C6 glioma cells were inoculated into the right caudate nucleus, and the growth of the tumor was confirmed by MRI at 1 week and 2 weeks after inoculation, and at 15 days 14 Cdoladazole (PR350) was dissolved in 3 mg / Kg normal saline and administered from the right common carotid artery. After 30 minutes, it was euthanized, and the brain was removed and divided into tumor part, ipsilateral cerebral cortex, opposite cerebral cortex, and middle cerebral cortex. Brain, cerebellum, and medulla. After the wet weight was determined, the fractions were chopped into 150 mg and dissolved in Solibable 1 mL. Add 0.5 mL of hydrogen peroxide heated at 60°C for 3 hours, heat at 60°C for 1 hour, add 10 mL of liquid scintillation cocktail, and count with a liquid scintillation counter 14 CPM for Fraction C. The results are shown in figure 1 . The control example was only given normal saline instea...

Embodiment 2

[0041]

[0042] according to figure 2 In the sequence shown, adopt the method of Example 1 to inoculate C6 glioma cells, confirm the growth of the tumor with MRI in 1 week and 2 weeks after inoculation, and dissolve doradazole (PR350) in 3 mg / Kg at 15 days Physiological saline was administered from the right common carotid artery, and the brain tumor (right head) was irradiated with 12Gy of radiation immediately, and the feeding was continued. On the 21st day, the size of the tumor was measured again by MRI. The control group was given normal saline only instead of the normal saline solution of doradazole. Radiation irradiation was carried out in both groups. The tumor sizes on day 21 of the doradazole-administered group and the control group are shown in image 3 . It was judged that the tumor shrank by a significant difference due to the radiosensitizing effect of doradazole.

[0043] The present invention can be used as a radiation sensitizer for brain tumors.

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Abstract

The invention provides a radiation sensitizer used for brain tumor, which is a radiation sensitizer in the radiation treatment of brain tumor and used for improving the radiation treatment effect in the radiation treatment of the brain tumor. Particularly, the invention provides a radiation sensitizer which takes 1-[2,3-dihydroxy-1-(hydroxy-methyl) propoxy]methyl-2-nitroimidazole shown in a formula (I) as an active component in the radiation treatment of the brain tumor.

Description

technical field [0001] The present invention relates to radiation sensitizers, and more specifically, to radiation sensitizers for brain tumor radiation therapy. Background technique [0002] It is known that 2-nitroimidazole derivatives have the effect of improving the radiosensitivity of hypoxic cancer cells in the treatment of radiation cancer. However, clinical trials were conducted on chemical agents, but the clinical trials were discontinued due to neurotoxicity (see, for example, Non-Patent Document 1). Thereafter, the development of a drug that does not distribute in nerve tissue but only increases the radiation sensitivity of hypoxic cancer cells has been continued (for example, refer to Patent Document 1), and a drug that hardly distributes in nerve cells but only sensitizes hypoxic cancer cells has been developed. 1-[2,3-Dihydroxy-1-(hydroxymethyl)propoxy]methyl-2-nitroimidazole in cancer cells (for example, refer to Patent Document 2). Since there are 2 chiral ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4164A61P35/00
Inventor 稻波修浅沼武敏辻谷典彦久保田信雄
Owner POLA PHARMA
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