Application of high pressure homogenate astragalus extract in preparation of nuclear emergency oral uranium excretion and radiation damage prevention medicine

Abstract

Existing nuclear emergency uranium excretion-promoting drugs are mostly intravenous chemical chelators, which have limitations in administration and high organ toxicity. Conventional radiation protection drugs only provide single-function antioxidant protection and cannot simultaneously promote radionuclide excretion and protect against radiation damage, making it difficult to meet the needs of rapid intervention at large-scale nuclear accident sites. This invention discloses a novel pharmaceutical application of high-pressure homogenized Astragalus extract, using physical modification to obtain nano-Astragalus extract, which has no chemical residues and good biosafety. This extract can chelate hexavalent uranyl ions in gastric juice through hydroxyl groups, blocking intestinal absorption, promoting uranium excretion in feces, and reducing uranium accumulation in organs; at the same time, it activates the body's antioxidant system, scavenges radioactive free radicals, and alleviates uranium exposure-induced oxidative stress damage. This invention explores a new application of this nano-Astragalus extract in oral nuclear emergency protection drugs, which is convenient to use, highly safe, and suitable for scenarios such as nuclear power plant leaks, depleted uranium contamination, and radioactive operations, possessing good public health emergency value and industrialization prospects.

Description

Technical Field

[0001] This invention belongs to the field of radiation medicine and nuclear emergency drug application technology, specifically involving a novel use of nano-modified Astragalus extract in the preparation of oral emergency drugs that have both uranium expulsion-promoting and radiation oxidative damage protection effects. Background Technology

[0002] Nuclear leaks and the use of depleted uranium weapons can easily cause widespread uranium contamination in the human body. Once uranium enters the body, it accumulates continuously and causes oxidative stress and organ damage, seriously threatening human health. Existing protective drugs have significant technical shortcomings: traditional uranium chelating agents can only be administered intravenously, which is cumbersome and cannot meet the needs of rapid emergency intervention for large numbers of people at nuclear accident sites. Furthermore, they can easily cause the loss of trace elements and damage to liver and kidney function. Conventional radiation protection drugs only have a single antioxidant effect and lack the ability to chelate and promote the excretion of uranium ions, thus failing to address the root cause of uranium accumulation in the body.

[0003] Currently, there is a lack of oral natural medicines suitable for nuclear emergency scenarios on the market. There are no dedicated formulations that simultaneously achieve the dual effects of "intestinal uranium excretion blockade + organ radiation damage protection," making it impossible to balance the convenience of emergency administration with the comprehensive protection against damage. Therefore, exploring application scenarios for novel, safe, orally administered nuclear emergency medicines with dual effects has significant clinical value and social implications. Summary of the Invention

[0004] Purpose of the invention: To address the shortcomings of existing nuclear emergency protective drugs, such as limited administration, single function, and significant toxic side effects, this invention provides a novel pharmaceutical application for high-pressure homogenized nano-Astragalus extract, developing its application in the preparation of oral uranium efflux promoters and radiation damage protection drugs, achieving the triple advantages of convenient oral administration, efficient efflux promotion, and oxidative damage protection, and adapting to various nuclear contamination emergency scenarios.

[0005] Technical Solution: Application of high-pressure homogenized Astragalus extract HP-ARE in the preparation of oral uranium excretion-promoting and radiation damage protection drugs for nuclear emergency; HP-ARE is a nanoproduct obtained by homogenization modification of Astragalus aqueous extract under constant temperature and high pressure in a pure water system at 200 bar, with a particle size of 8~10 nm, no chemical residues, and excellent biocompatibility. The drug has dual core therapeutic indications: First, oral intervention for uranium contamination in the digestive tract: After oral administration, the drug can remain stable in an artificial gastric fluid environment. Through the formation of stable five-membered chelate rings with uranyl ions by hydroxyl and carboxyl groups on the molecular surface, it efficiently complexes UO2²⁺ using the Langmuir monolayer pseudo-secondary chemisorption mechanism, blocking the absorption of uranyl ions in the intestine, promoting the excretion of uranium contaminants in the body with feces, and significantly reducing the accumulation of radioactive uranium in the kidneys, lungs, and bones; Second, protection against uranium exposure-induced radiation oxidative damage: The drug can upregulate the activity of SOD and CAT antioxidant enzymes in the body, reduce the content of MDA oxidative stress products, effectively remove reactive oxygen free radicals generated by nuclear radiation, reduce oxidative damage to the kidneys and lungs caused by uranium exposure, and achieve radiation damage protection.

[0006] The drug is an oral dosage form, including oral dry powder and aqueous oral suspension. It can be supplemented with conventional food-grade pharmaceutical excipients such as pharmaceutical starch, and is suitable for various scenarios such as nuclear power plant leak emergency response, intervention in depleted uranium war zones, and daily protection of radiation workers.

[0007] Beneficial effects: First, this invention is the first to develop the dual medical applications of HP-ARE, simultaneously achieving radionuclide excretion promotion and radiation oxidative damage protection, filling the market gap for natural oral nuclear emergency drugs and breaking through the limitations of traditional drugs with single functions; Second, the drug is in oral dosage form, making administration convenient and requiring no professional medical care, enabling large numbers of people at nuclear accident sites to take it independently in emergency situations, and is suitable for large-scale nuclear emergency intervention scenarios; Third, the pure Chinese herbal modified raw materials are non-toxic and residue-free, and will not cause the loss of essential trace elements in the human body, making its safety far superior to traditional chemical chelating agents, and it can be used for short-term emergency intervention and long-term low-dose radiation protection; Fourth, the raw material cost is low, the preparation process is simple, it can be mass-produced, and it is convenient to store and transport, making it suitable as a routine emergency reserve material for nuclear power plants, research institutions, and war zones. Attached Figure Description

[0008] Figure 1 The graph shows the effect of ARE and HP-ARE on the survival rate of NRK-52E cells.

[0009] Figure 2 The effects of ARE and HP-ARE on the survival rate of uranium-poisoned NRK-52E cells.

[0010] Figure 3 A comparison of uranium removal rates in feces / urine of ARE and HP-ARE mice.

[0011] Figure 4 Comparison of uranium accumulation in the kidneys, lungs, and femurs of ARE and HP-ARE mice. Detailed Implementation

[0012] The following detailed description of the drug uses, applicable scenarios, and protective effects of the present invention is provided in conjunction with specific application examples. All examples are for illustrative purposes only and are not intended to limit the scope of protection of the present invention.

[0013] Example 1: An acute gastrointestinal uranium contamination model was established using healthy SPF-grade mice. HP-ARE raw materials prepared using the optimal process were formulated into an oral aqueous suspension with a concentration of 20 mg / mL. Mice were administered the medication by gavage once daily for 3 consecutive days immediately after modeling. Various indicators were measured after 72 hours of standard feeding. Results showed that the oral HP-ARE formulation rapidly complexes uranyl ions in the gastrointestinal tract, forming a stable, poorly absorbed chelate. This significantly increased the uranium excretion rate in mouse feces and substantially reduced the accumulation of radioactive uranium in the kidneys and lungs. It can achieve rapid emergency intervention to promote excretion in acute nuclear contamination scenarios. The administration is convenient, the onset of action is rapid, no professional medical intervention is required, and it is suitable for large-scale self-administered emergency use.

[0014] Example 2: To address persistent oxidative radiation damage caused by uranium exposure, a low-dose, multiple-dose administration regimen was used, with oral administration of HP-ARE preparation for 7 consecutive days. Results showed that the activities of SOD and CAT antioxidant enzymes in the serum and organs of experimental mice remained elevated, while the content of MDA oxidative damage products significantly decreased. The body's oxidative stress level was effectively regulated, significantly alleviating chronic organ damage induced by uranium radiation and achieving a synergistic effect of promoting detoxification and repairing damage.

[0015] Comparative Example 1: A clinically commonly used EDTA-CaNa2 chelating agent was used as a control, and uranium-contaminated mice were treated with the same dose. The results showed that chemical chelating agents only have a single excretion-promoting effect, no radiation damage protection capability, and long-term administration can cause the loss of trace elements and mild damage to liver and kidney function. In contrast, the drug of this invention has dual protective effects, no toxic side effects, and can be taken orally for emergency use. Its comprehensive application effect is significantly better than that of traditional drugs.

[0016] Summary of application effects: The pharmaceutical applications of the nano-Astragalus extract disclosed in this invention break through the bottlenecks of traditional nuclear emergency drugs, such as single function, limited administration, and poor safety. Relying on pure natural physically modified raw materials, it achieves the triple advantages of convenient oral administration, efficient excretion promotion, and radiation damage protection. It is suitable for various nuclear pollution emergency scenarios and has extremely high industrialization and emergency application value.

Claims

1. The application of high-pressure homogenized Astragalus extract HP-ARE in the preparation of oral uranium elution promoters and radiation damage protectants for nuclear emergency use, characterized in that... The HP-ARE is a nanoproduct obtained by homogenizing and modifying the water-extracted alcohol precipitate of Astragalus membranaceus under constant temperature and high pressure in a 200 bar pure water system. The drug has dual therapeutic functions: first, it is used orally to promote the excretion of hexavalent uranium contamination in the human digestive tract by chelating uranyl ions in the intestine, blocking absorption, promoting fecal excretion, and reducing the accumulation of radioactive uranium in the body; second, it is used to protect against radiation oxidative damage caused by uranium exposure by upregulating the activity of antioxidant enzymes in the body and reducing oxidative stress damage to organs. The drug is in oral dosage form.

2. The application according to claim 1, characterized in that, The oral dosage forms are dry powder and aqueous oral suspension, with only food-grade conventional pharmaceutical excipients added and no toxic additives added.

3. The application according to claim 1, characterized in that, The drug is applicable to scenarios including emergency intervention for radioactive leaks in nuclear power plants, protection of people contaminated by depleted uranium weapons, and daily low-dose radiation protection for workers in radioactive laboratories.

4. The application according to claim 1, characterized in that, The adsorption mechanism of HP-ARE with uranyl ions conforms to the Langmuir isothermal adsorption model, with chemical chelation adsorption as the core mechanism.

Images