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Alkaline amino acid salt of Glycididazole acid, preparation and application

A technology of glycidazole acid arginine salt and glycidazole acid lysine salt, which is applied in the field of medicine, can solve the problems of poor stability, side effects, poor water solubility of glycidazole acid, and achieves water solubility and Good stability, easy to use, avoid the effect of sodium retention

Inactive Publication Date: 2009-11-18
SHENZHEN HEPALINK PHARMA GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Molecular formula is C 18 h 22 N 7 o 10 Na, glycididazole sodium for injection, which has been approved for marketing, is a metal sodium salt compound of glycididazole acid, which is an ionic salt compound. When used, it is dissolved in normal saline and injected intravenously. The main product of its metabolism in the body is formazan Nitazole, but it should be noted that metronidazole can cause metabolic disorders such as sodium retention under the condition of excessive sodium salt intake. dissolved, which may cause some potential unforeseen side effects when using glycididazole sodium
[0005] The water solubility of glycidazole acid is poor, almost insoluble in water, which is very inconvenient in the preparation and application of medicines, and the metal ion salt compound of glycidazole acid has certain disadvantages. In addition, glycidazole acid itself is a diester Type compound, poor stability, ionic salt compounds such as glycidiazole sodium are ionized solutions in aqueous solution, easy to hydrolyze and produce impurities such as metronidazole, making it very inconvenient in drug application, in view of this, the purpose of the present invention is to provide glycine The non-metallic salt of Amidazole acid not only has better water solubility and stability in aqueous solution, but also avoids some side effects caused by excessive intake of sodium when using drugs

Method used

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  • Alkaline amino acid salt of Glycididazole acid, preparation and application
  • Alkaline amino acid salt of Glycididazole acid, preparation and application
  • Alkaline amino acid salt of Glycididazole acid, preparation and application

Examples

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Effect test

Embodiment 1

[0031] Example 1: Preparation of glycidazole arginine (1:1)

[0032] Take 8 grams (about 0.016mol) of glycididazole acid and add 30ml of absolute ethanol to make a suspension, and take another 2.8 grams (about 0.016mol) of L-arginine and add 20ml of water to dissolve it. The solution is slowly added dropwise to the suspension of glycididazole acid, and after adding completely, continue to shake and shake until the mixed solution is light yellow and clear, and then add about 150ml of absolute ethanol, and a white emulsion will appear. Place the emulsion in the refrigerator overnight to allow it to precipitate, then remove the supernatant, vacuum-dry the light yellow precipitate below 45°C to constant weight to obtain a light yellow solid powder, wash with absolute ethanol for 2 to 3 times, and evaporate under reduced pressure. After removal of ethanol, the high-quality product of glycidazole arginine salt (abbreviated as glycidazole arginine) with a salt-forming ratio of 1:1 is...

Embodiment 2

[0033] Example 2: Stability experiment of glycidiazole arginine in aqueous solution

[0034] The glycidiazole arginine prepared in Example 1 has excellent water solubility, with a solubility greater than 30%, which can fully meet the application in the preparation of medicaments. The aqueous solution stability of glycidiazole arginine and glycidiazole sodium is verified by experiments.

[0035] Experimental method: Accurately weigh glycididazole arginine and glycididazole sodium, use distilled water to make solutions with a concentration of about 5%, and adjust the pH of the solution to 7.5±0.2, and measure the two solutions every 5hr The concentration of glycidazole arginine and glycididazole sodium was observed.

[0036] Content Determination Method: Determination according to high performance liquid chromatography. The system suitability test uses octadecylsilane bonded silica gel as the filler, acetonitrile-0.05mol / L ammonium acetate (pH7.1) (15:85) as the mobile phase, ...

Embodiment 3

[0039] Embodiment 3: Animal experiments are used to further observe the pharmacodynamic effect of glycidazole arginine of the present invention.

[0040] Experimental method: (1) The animal model adopts the C 57 / BL inbred mice, the tumor cell suspension was transplanted into the hind limbs of the mice, and the tumor grew to 200-400mm 3 used for experiments.

[0041] (2) Each group of 8 animals was divided into four groups, which were blank group, single radiation group, glycidazole sodium+radiation group, glycidazole arginine+radiation group. The blank group did not receive any treatment; the radiation group alone received gamma-ray irradiation at a dose of 8 Gy / time / 3 days; the glycididazole sodium + radiation group received intraperitoneal injection of glycididazole sodium 0.3 mmol / kg, and then irradiated gamma-rays , the dose was 8Gy / time / 3 days; the glycidazole-arginine+radiation group was given intraperitoneal injection of glycidazole-arginine 0.3mmol / kg, and then γ-ra...

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Abstract

The present invention relates to double salt compound of glycididazole acid and basic amino acid, including glycididazole acid arginine salt, glycididazole acid lysine salt, glycididazole acid ornithine salt, glycine Bisazole acid histidine salt, its preparation method and application of tumor radiochemotherapy sensitizer. Its preparation method is to contact glycididazole acid with basic amino acid in a liquid environment to form a salt, and then remove the liquid. Using basic amino acids as safe double salt ligands provides a new compound form with better water solubility and stability for the application of glycididazole in medicine, which is more convenient for the preparation and use of medicaments; moreover, The basic amino acid salt of glycididazole acid is a non-sodium ion salt, which avoids the occurrence of adverse reactions such as sodium retention and other electrolyte metabolic disorders caused by excessive sodium intake.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a radiochemotherapy sensitizer-a basic amino acid double salt compound of glycididazole acid, its preparation method and application. Background technique [0002] Radiation and chemotherapy are important methods in the treatment of tumor diseases. The effect of radiotherapy and chemotherapy directly affects the recovery and survival of patients. There are many factors that affect the curative effect of radiation and chemotherapy. One of the important reasons is that tumor tissue contains 10 ~50% hypoxic cells, these hypoxic cells are about 3 times more resistant to radiation and chemotherapy drugs than aerobic cells and normal cells in tumors, and have obvious resistance to radiation and chemotherapy drugs, so in routine During radiotherapy and chemotherapy dose treatment, hypoxic cells cannot be effectively killed and become a "shelter" for tumor metastasis and survival. This is...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D233/91A61K31/4164A61P35/00
Inventor 杨喜鸿
Owner SHENZHEN HEPALINK PHARMA GRP CO LTD