Use of ink pterin and metabolites thereof to treat radiation exposure

A technique for mopterin, biopterin, used in the field of treatment of subjects exposed to radiation

Pending Publication Date: 2022-05-27
PTC医疗MP公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, as observed with survivors of Chernobyl, patients who survive ARS of the hematopoietic and GI systems often die from advanced damage to the lungs and heart

Method used

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  • Use of ink pterin and metabolites thereof to treat radiation exposure
  • Use of ink pterin and metabolites thereof to treat radiation exposure
  • Use of ink pterin and metabolites thereof to treat radiation exposure

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0101] Example 1. Treatment of C57L / J mouse group

[0102] animal

[0103] Both male and female C57L / J wild-type 6-8 week old mice were purchased from Jackson Laboratory (BarHarbor, ME). Mice were housed on a 12:12 h light-dark schedule with ad libitum access to water and food. These experiments were performed in accordance with the Guide to Laboratory Animals for Biomedical Research (Revised 2011) published by the National Institutes of Health. The study protocol was approved by the Institutional Animal Care and Use Committee of Virginia Commonwealth University.

[0104] Experimental treatment plan

[0105] Equal numbers of male and female mice were assigned to each group. Mice were subjected to 5 Gy total body irradiation (TBI) using a Varian 21EX LINAC (Palo Alto, CA) under ketamine / xylazine anesthesia (100 mg / kg and 10 mg / kg, respectively), followed by immediate thoracic supplementation 6.5 Gy dose for a total chest dose of 11.5 Gy. Twenty-four hours after irradiatio...

Embodiment 2

[0106] Example 2. Assessment of Cardiac Function

[0107] echocardiography

[0108] Under light anesthesia (30 mg / kg sodium pentobarbital), all mice underwent transthoracic echocardiography at baseline (before irradiation (IR)), 8, 30, 60, 90, and 180 days. Echocardiography was performed with a Vevo770 imaging system (VisualSonics, Toronto, Ontario, Canada) and a 30 MHz probe. The heart is shown in B-mode from parasternal short-axis and apical views. Left ventricular (LV) end-diastolic diameter (EDD), LV end-systolic diameter (ESD), LV anterior wall diastolic thickness (AWDT) and LV posterior wall diastolic thickness (PWDT), LV anterior wall systolic thickness (AWST) and Posterior LV systolic thickness (PWST) was measured in M ​​mode according to the recommendations of the American Society of Echocardiography. LV ejection fraction (EF) and LV mass were calculated from measurements of wall thickness and chamber diameter. As mentioned earlier, LVEF is derived using Teicholz'...

Embodiment 3

[0111] Example 3. Assessment of Pulmonary Function

[0112] Assessment of lung injury by respiratory rate

[0113] Beginning at week 6, respiratory rate was measured every other week using the Mouse Ox system (STARR Life Sciences Corp., Allison Park, PA). Animals were placed under ketamine / xylazine anesthesia and shaved in the analysis area. Ten minutes after injection, the animal was placed in the supine position with the transducer clamped to the upper thigh. The respiratory rate was recorded for 3 minutes. Respiratory rate was calculated using an algorithm in the Mouse Ox software.

[0114] SP and BH4 reduce radiation-induced lung function loss

[0115] The mouse respiration rate was measured using the MouseOx system as exposure, exposure and SP ( Figure 9 ) and irradiation with BH4 ( Figure 5 ) measure of respiratory function in mice. Mice receiving 1 mg / kg / day SP or 5 mg / kg BH4 for 6 days had a significant delay in the development of lung lesions compared to vehi...

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Abstract

The present invention provides methods for treating radiation exposure in a subject by administering Inopterin, Tetrahydrobiopterin, or Dihydrobiopterin.

Description

[0001] Statement Regarding Federally Funded Research [0002] This invention was made with government support under Grant No. R01 AI133595 awarded by the National Institutes of Health (NIH). The government has certain rights in this invention. [0003] Background of the Invention [0004] Whether through acts of terrorism or nuclear accidents, the threat of a radiological disaster represents a potentially catastrophic public health emergency that underscores the need to develop medical countermeasures to mitigate whole-body radiation-induced injury and death. The initial health consequence of total body radiation (TBI) exposure is acute radiation syndrome (ARS) in the most radiation-sensitive organs, and survival from this exposure depends on stem and progenitor cells in the hematopoietic system and epithelial cells in the gastrointestinal system degree of damage. Hematopoietic growth factors, electrolytes and fluids, blood transfusions and antibiotics are all advances in the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/519A61P43/00
CPCA61K31/519A61P43/00A61P39/00
Inventor E·梅扎罗马C·拉本德R·米克尔森V·亚科夫列夫N·史密斯
Owner PTC医疗MP公司
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