Application and drug of tetrahydrobiopterin

A technology of tetrahydrobiopterin and drugs, applied in the direction of drug combination, respiratory diseases, etc., to achieve the effect of enhancing anti-oxidation

Pending Publication Date: 2019-10-22
鞍山市肿瘤医院 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the protective and therapeutic functions of the BH4 synthesis pathway have been reported in radiation-induced skin injury, cardiovascular system and other diseases, there has been no application of BH4 in the prevention and treatment of radiation-induced lung injury at home and abroad. Much research and exploration

Method used

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  • Application and drug of tetrahydrobiopterin
  • Application and drug of tetrahydrobiopterin
  • Application and drug of tetrahydrobiopterin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] The oxidative inactivation of BH4 can be caused after the ionizing radiation of embodiment 1

[0036] The BH4 powder was dissolved in double-distilled water with a final concentration of 1 μg / ml. The aqueous solution was divided into two groups, and after 0Gy and 10Gy X-ray irradiation, the ultraviolet absorption spectrum was detected. BH4 has three characteristic absorption peaks at 230nm, 280nm and 330nm respectively. The spectrum of BH4 was detected immediately after 10Gy of X-ray irradiation, and its spectrum did not change significantly. With the increase of time after irradiation, the characteristic absorption peaks at 230nm, 280nm and 330nm of BH4 decreased gradually.

[0037] Such as figure 1 (attachment1 figure 1 ), the results showed that ionizing radiation itself did not cause changes in the structure of BH4, but the structure of BH4 changed with the increase of time after irradiation.

Embodiment 2

[0038] Example 2 Anti-radiation effect test of BH4 on lung cells

[0039] 1. BH4 reverses the reduction of NO caused by ionizing radiation

[0040] Human embryonic lung fibroblasts in the exponential growth phase were inoculated in 96-well plates and cultured for 12 hours. PBS or 12.5 μmol / L BH4 were added 24 hours before irradiation. Each group had 4 parallel samples, and the experiment was repeated 3 times. Afterwards, an absorbed dose of 20Gy X-rays was irradiated. Aspirate the medium 24 hours after exposure, add 100 μL of diluted DAF-FMDA to each well (dilute DAF-FMDA with DAF-FMDA diluent according to 1:1000, so that the final concentration is 5 μmol / L), and incubate in the incubator 20min. Wash three times with PBS to fully remove DAF-FMDA that did not enter the cells. Detection by microplate reader.

[0041] Such as figure 2 (P<0.05), the results showed that the BH4 treatment group had no effect on the NO content of the 0Gy group, but could significantly reverse ...

Embodiment 3

[0048] Example 3 Anti-radiation effect test of BH4 on mouse lung tissue

[0049] Male C57 mice aged 6 to 8 weeks were purchased from Shanghai Slack Experimental Animal Co., Ltd., and each mouse was anesthetized by intraperitoneal injection of 4% chloral hydrate according to 1% of its body weight, and small animal positioning was performed using a small animal precision irradiation device Afterwards, the right lung was precisely irradiated with an aperture of 5mm, so that 100% of the volume reached the prescribed dose of 20Gy, and a mouse radiation-induced lung injury model was established, and then the mice were randomly divided into 2 groups (5 in each group):

[0050] 1) Give mice a tail vein injection of 100 μL of BH4 aqueous solution at a concentration (1 mg / kg); 2) Give mice a tail vein injection of 100 μL of PBS.

[0051] After 7 days of irradiation, C57 mice were sacrificed by cervical dislocation. The right lung tissue was taken, rinsed repeatedly with normal saline, ...

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Abstract

The invention relates to application and a drug of tetrahydrobiopterin. It is found that tetrahydrobiopterin (BH4) has the prevention and treatment effect on radiation injury of human lung cells and animal model lung tissues, and can enhance oxidation resistance of the cells and cell proliferation capacity after radiation. The tetrahydrobiopterin or the drug containing the tetrahydrobiopterin canbe used for preventing and treating human acute lung radiation injury, and has the important significance and application value in coping with nuclear and radiation accidents, nuclear emergencies, reduction of the lung radiation injury effects on tumor radiation patients and the like.

Description

technical field [0001] The invention relates to the application and medicine of tetrahydrobiopterin and belongs to the field of biotechnology. Background technique [0002] Radiation-induced lung injury is a common complication after radiotherapy for thoracic tumors and pretreatment for bone marrow transplantation. In addition, since the lung is a radiation-sensitive organ, occasional nuclear radiation accidents in normal times or nuclear radiation damage in wartime often involve the lungs, resulting in radiation-induced lung injury. In tumor radiotherapy, a considerable number of patients will have different degrees of radiation-induced lung injury. Radiation lung injury is more serious in patients with thoracic malignancies, such as lung, breast and esophageal cancer. Severe radiation-induced lung injury may affect the smooth progress of radiotherapy and the quality of life of patients. [0003] Radiation-induced lung injury refers to a series of pathological changes in...

Claims

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Application Information

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IPC IPC(8): A61K31/519A61P11/00
CPCA61K31/519A61P11/00
Inventor 李旭刚张镇曹建平冯阳高晶晶张舒羽
Owner 鞍山市肿瘤医院
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