Application of ultraviolet light in detoxification of dipyridyl toxicants
By using direct irradiation of UV light at a specific wavelength or combined with blood purification, the problem of toxic removal in patients with bipyridine pesticide poisoning is solved, significantly reducing the mortality rate and improving the prognosis.
Patent Information
- Application Number
- CN202411862965.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-17
- Publication Date
- 2025-03-18
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
The prior art is difficult to effectively remove toxic substances from patients with bipyridine pesticide poisoning, especially in the absence of professional equipment and technical teams in rural areas, resulting in a high mortality rate.
UV light of a specific wavelength is used to directly irradiate the epidermis of a poisoned patient, or combined with blood purification technology to degrade bipyridine poisons by irradiating plasma through external ultraviolet light.
Ultraviolet light exposure can rapidly degrade bipyridine poisons, significantly reduce liver and kidney damage after poisoning, improve patient prognosis, and provide a simple and easy-to-use treatment technology.
Smart Images
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Abstract
Description
Technical Field
[0001] The invention relates to the field of medical technology, and in particular to the application of ultraviolet light in the detoxification of bipyridine poisons. Background Art
[0002] Pesticide poisoning is a major public health and clinical problem worldwide. Bipyridyl herbicides represented by diquat (DQ) and paraquat (PQ) are the most common pesticide poisoning varieties in my country, causing about 85% of herbicide-related deaths. After my country banned the sale of PQ aqueous solution in 2016, DQ poisoning incidents increased significantly. At present, the clinical treatment methods for DQ poisoning mainly include: reducing the absorption of poisons, accelerating the excretion of poisons by means of blood purification, antioxidant drugs and other symptomatic and supportive treatments, but the overall treatment effect is poor, and the mortality rate remains high, much higher than the mortality rate of acute poisoning. The main reasons include: 1. Since blood purification measures as the main means of poison removal require professional equipment and technical teams, it is difficult to carry out early intervention and poison removal in rural areas where DQ poisoning is common; 2. Suicide is a common cause of severe DQ poisoning. Patients often have a large poisoning dose, and blood purification means have limited removal efficiency, need to be performed multiple times, and often have poor prognosis.
[0003] Light therapy (Light Terapyor Photherapy) refers to the method of using sunlight or light of a specific wavelength to treat diseases, such as the use of "psoralen-ultraviolet A" photochemotherapy to treat psoriasis, mycosis fungoides, etc., and photodynamic therapy based on photosensitizers such as porphyrins to treat non-tumor diseases and various types of cancer. Light therapy has the advantages of being non-invasive, having few side effects, being fast-acting, and being low-cost. At the same time, the possibility of combining it with other treatment options makes it widely used in many medical fields. It is a treatment method with a wide range of applications and is relatively safe.
[0004] At present, there are no reports on the treatment of poison removal based on ultraviolet light, and there is a lack of related basic and applied research. Therefore, the research and development of a simple and easy direct treatment technology that can be used alone, or an in vitro detoxification technology that can be combined with blood purification, is of great significance to improve the survival rate of patients poisoned by DQ and its similar pesticides and improve the prognosis of patients. Summary of the invention
[0005] The purpose of the present invention is to provide an application of ultraviolet light in the detoxification of bipyridine poisons. Specifically, ultraviolet light is directly irradiated on the epidermis of poisoned animals or patients, or ultraviolet light is used in combination with blood purification to detoxify technology, both of which can quickly degrade bipyridine poisons (such as diquat or paraquat), providing a technical solution for efficient blood purification and improved prognosis after poisoning.
[0006] The objective of the present invention is achieved through the following technical solutions:
[0007] Application of ultraviolet light in the detoxification of bipyridine poisons.
[0008] As some feasible embodiments of the present application, after acute poisoning, while using a blood purification device, ultraviolet light of a specific wavelength is used to irradiate plasma / blood in an in vitro environment, that is, a blood purification device and in vitro ultraviolet light irradiation are used in combination to degrade bipyridine poisons.
[0009] As some possible embodiments of the present application, the blood purification device is selected from hemodialysis, hemofiltration, hemoperfusion, continuous blood purification equipment, plasma exchange, and immunoadsorption equipment.
[0010] As some possible implementation methods of the present application, before ultraviolet light irradiation of plasma, a photocatalyst, such as titanium dioxide, is first added to the plasma to enhance the degradation effect of bipyridine poisons.
[0011] As some possible implementation methods of the present application, in the blood purification device and in vitro ultraviolet irradiation combined technology, the ultraviolet light wavelength range is less than 310nm. Preferably, the ultraviolet light wavelength range is 190 to 310nm. More preferably, the ultraviolet light wavelength is 254nm.
[0012] As some possible implementation methods of the present application, after acute poisoning, ultraviolet light of a specific wavelength is directly irradiated to the epidermis.
[0013] As some possible implementation methods of the present application, in the technology of direct ultraviolet light irradiation on the epidermis, the ultraviolet light wavelength range is less than 310nm. Preferably, the ultraviolet light wavelength range is 190 to 310nm. More preferably, the ultraviolet light wavelength is 254nm.
[0014] As some feasible implementation methods of the present application, in the technology of direct ultraviolet light irradiation to the epidermis, the single ultraviolet light irradiation time is less than 4 hours, and the treatment effect is best in the early stage of poisoning.
[0015] As some feasible implementation methods of the present application, in the technology of direct ultraviolet light irradiation to the epidermis, the patient first supplements common vitamins or applies a photocatalyst on the skin surface, or both supplements common vitamins and applies a photocatalyst. Among them, common vitamins are vitamins A, B, C, D vitamins, etc., and photocatalysts are titanium dioxide, etc. In this scheme, by supplementing vitamins or applying a photocatalyst before ultraviolet light irradiation, it is possible to effectively prevent cells from being excessively damaged under ultraviolet light irradiation, and at the same time, it is possible to further accelerate the degradation of bipyridine poisons under irradiation with lower light intensity, thereby improving the detoxification effect. As some feasible implementation methods of the present application, the bipyridine poison is diquat or paraquat.
[0016] Compared with the prior art, the present invention has the following beneficial effects:
[0017] The present invention discloses a new application based on ultraviolet light-promoted degradation for detoxification of bipyridine poisons such as diquat and paraquat. By optimizing the wavelength of ultraviolet light source, verifying the effects of different matrices and concentrations on the photodegradation of diquat and paraquat, and evaluating the safety and effectiveness of direct irradiation of animals, it is confirmed that ultraviolet light irradiation with a suitable wavelength can effectively reduce the blood drug concentration after diquat poisoning, significantly reduce the liver and kidney damage of mice after diquat poisoning, and has a positive effect on prognosis. The present invention can provide a new solution for the treatment of acute poisoning, and is intended to solve the clinical bottleneck problem of no specific treatment for diquat poisoning and high mortality rate, lay a foundation for the development of new diquat poisoning treatment methods, and also provide new technical support for the treatment and detoxification of related similar poisons (such as paraquat, etc.). BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 :Effects of different light sources (190nm, 254nm, 310nm, 365nm and natural light) on the photodegradation of diquat in vitro;
[0019] Figure 2 :Effects of different matrices (water, plasma) and concentrations on the in vitro photodegradation of diquat;
[0020] Figure 3 :The effect of ultraviolet irradiation on the blood concentration of diquat in mice exposed to it;
[0021] Figure 4 :Effects of ultraviolet irradiation on liver and kidney damage in mice exposed to diquat;
[0022] Figure 5 :Effects of different light sources (254nm, 365nm and natural light) on the photodegradation of paraquat in vitro;
[0023] Figure 6 :Effects of different matrices (water, plasma) and concentrations on the photodegradation of paraquat in vitro. DETAILED DESCRIPTION
[0024] Example 1 Evaluation of the effect of ultraviolet light on promoting the degradation of diquat in vitro
[0025] (1) Selection of UV light source
[0026] Light is a photon in a specific frequency band. Generally speaking, visible light is an electromagnetic wave that can be seen by humans. Its wavelength range is generally between 360-400nm and 760-830nm, while the range of ultraviolet light is usually between 100-400nm. Here, we explored the effects of different light sources on the degradation of diquat and paraquat. A standard aqueous solution with a diquat concentration of 1ug / mL was irradiated with natural light, light sources with a wavelength of 365nm, a wavelength of 310nm, a wavelength of 254nm, and a wavelength of 190nm. The irradiation time was 0.5, 1, 2, 4, 8, and 16h. Samples were taken for chromatography-mass spectrometry (LC-MS) detection. The results are shown in Figure 2. Figure 1 .
[0027] The results show that under sunlight, natural light and light with a wavelength of 365nm, diquat hardly undergoes photodegradation, and cannot achieve the purpose described in the patent of this invention; under ultraviolet light with wavelengths of 310nm, 254nm and 190nm, diquat aqueous solution can be rapidly degraded, laying the foundation for the in vitro removal of diquat; at the same time, the results show that the photodegradation ability of wavelengths of 254nm and 190nm is better than that of wavelength 310nm, but ultraviolet rays with a wavelength of 180-190nm react with air to produce ozone with strong oxidizing properties, which is harmful to the human body. Ultraviolet light sources with a wavelength of 254nm are the most easily available ultraviolet rays, with high commercialization, and have been used in many fields such as environmental disinfection and sterilization, agriculture and food, and anti-counterfeiting technology. Taking all factors into consideration, the subsequent ultraviolet irradiation experiments plan to use ultraviolet light sources with a wavelength of 254nm for further research.
[0028] (2) Effects of different matrices and different concentrations of diquat standard solutions on photodegradation
[0029] Using ultraviolet light with a wavelength of 254nm as the irradiation light source, the effects of different concentrations (0.5, 1.0, 2.0μg / mL) of diquat standard solution on photodegradation in different matrices (water, plasma) were investigated. The results are as follows Figure 2 The results showed that the in vitro degradation effect of diquat described in the present invention can be achieved by using 254 nm light in different substrates and at different concentrations.
[0030] Example 2 Evaluation of the therapeutic effect of direct irradiation of animals with ultraviolet light to promote diquat degradation
[0031] (1) Effects of UV irradiation on blood concentrations of diquat in mice exposed to diquat
[0032] Monitoring the blood concentration level of poisons can help to better understand and deal with poisoning cases, and more accurately determine the nature, severity and prognosis of poisoning. The experiment used male BALB / c mice, SPF grade, 8-9 weeks old, weighing 22-25g, purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd. (Beijing, China); administration method: intravenous injection of diquat at a toxic dose of 50 mg / kg; treatment method: 254nm irradiation; grouping: blank group (irradiation treatment only, no drug administration), group treated without irradiation after drug administration, and group treated with irradiation after drug administration, 6 mice in each group; blood was collected from the orbital venous plexus, and after blood collection, centrifuged at 3500rpm for 10 minutes, and the supernatant plasma sample was taken for LC-MS detection of blood drug concentration. The results are as follows Figure 3 The results showed that the blood concentration of diquat in the irradiation treatment group was lower than that in the untreated group (n=6) at 0.5, 1, 2, and 4 hours after poisoning, indicating that direct ultraviolet irradiation can significantly reduce the early blood concentration of diquat after poisoning (P<0.001).
[0033] The above results prove the safety of ultraviolet irradiation, which can effectively reduce the concentration of poisons after diquat poisoning and achieve therapeutic effects.
[0034] (2) Effects of UV irradiation on liver and kidney damage in mice exposed to diquat
[0035] After human poisoning, the kidney is the main excretion organ after diquat absorption and is also the main target organ of damage. In addition, diquat can cause liver damage. Therefore, liver (aspartate aminotransferase (AST), alanine aminotransferase (ALT)) and kidney (serum creatinine (CrEA) and urea (U1REA)) function monitoring is an important clinical laboratory auxiliary diagnostic indicator after diquat poisoning ("Expert Consensus on Diagnosis and Treatment of Acute Diquat Poisoning" 2020 edition). The experiment used male BALB / c mice, SPF grade, 8-9 weeks old, weighing 22-25g, purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd. (Beijing, China); administration method: intravenous injection of diquat at a toxic dose of 50 mg / kg; treatment method: 254nm irradiation; grouping: blank group (irradiation treatment only, no drug administration), drug administration without irradiation treatment group, drug administration after irradiation treatment group, 6 mice in each group; orbital venous plexus blood was collected, and after blood collection, centrifuged at 3500rpm for 10 minutes, and the supernatant serum sample was taken for biochemical analysis. The results are shown in Figure 4 The results showed that after diquat administration, liver and kidney markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (CrEA) and urea (UREA) increased significantly after 4 hours, indicating significant liver and kidney damage. After treatment with ultraviolet light at a wavelength of 254nm, the degree of liver and kidney damage in mice was significantly reduced (P < 0.001), proving the therapeutic effect of ultraviolet light irradiation on diquat-exposed mice.
[0036] Example 3 Evaluation of the effect of ultraviolet light on promoting paraquat degradation in vitro
[0037] (1) Selection of UV light source
[0038] Paraquat is a bipyridine compound with a similar structure to diquat. We irradiated a standard blood sample with a paraquat concentration of 500 ng / mL with sunlight, natural light, 365 nm wavelength, and 254 nm wavelength light for 0.5, 1, 2, 4, and 8 seconds, and then took samples for LC-MS detection. The results are as follows: Figure 5 .
[0039] The results showed that the photodegradation behavior of paraquat was similar to that of diquat. Within 8 hours of irradiation with natural light and ultraviolet light of a wavelength of 365nm, the concentration of paraquat did not change significantly, and almost no photodegradation occurred, which could not achieve the purpose of the patent of this invention. However, under ultraviolet light of a wavelength of 254nm, the concentration of paraquat in the sampled blood continued to decrease, proving that ultraviolet light of a certain wavelength can promote the rapid degradation of paraquat in the blood, laying the foundation for the in vitro elimination of paraquat.
[0040] (2) Effects of different matrices and different concentrations of diquat standard solutions on photodegradation
[0041] Using ultraviolet light with a wavelength of 254nm as the irradiation light source, the effects of different concentrations (100, 500, 1000ng / mL) of diquat standard solution on photodegradation in different matrices (water, plasma) were investigated. The results are as follows Figure 6 The results showed that the paraquat in vitro degradation effect of the present invention can be achieved by using 254nm light under different matrices and different concentrations.
[0042] Example 4
[0043] In Example 2, the inventors found that long-term direct exposure to ultraviolet light can cause skin burns and produce related inflammatory reactions. On this basis, the inventors found that the relevant problems can be solved by any of the following methods. Specifically as follows:
[0044] 1) Give vitamin supplements (such as vitamin C, vitamin A, B vitamins and vitamin D) in advance, at least vitamin B, vitamin C and vitamin A, and the amount of each vitamin supplemented is the maximum daily dose of that vitamin. This method can reduce skin damage and allergic reactions caused by ultraviolet rays and free radicals;
[0045] 2) Select to apply the photocatalyst (titanium dioxide) on the surface of animal skin, with a coating thickness of 1 mm (during actual application, the coating thickness can be appropriately adjusted, with a thickness range of 0 mm < coating thickness ≤ 2 mm). Under lower light intensity, the degradation of diquat is further accelerated, thereby reducing skin damage. For example, conventional 25W 254nm wavelength ultraviolet light source can achieve the expected effect, but after applying the photocatalyst (titanium dioxide), only 10 to 20W of ultraviolet light is needed to achieve the same expected effect as the conventional 25W.
[0046] 3) Using the above method 1) and method 2) at the same time will produce better results.
[0047] In addition, in the in vitro irradiation studies of Examples 1 and 3, the inventors found that adding the photocatalyst to the plasma in advance can also achieve better results and improve the degradation capacity of diquat under the same light intensity.
[0048] Example 5
[0049] Based on the ultraviolet light conditions optimized and verified in Example 1, it is further used in conjunction with common blood purification equipment to accelerate the clearance rate of poisons.
[0050] The experiment used male Landrace pigs, 12 to 18 months old, which were fed daily and had free access to drinking water. The ambient temperature was 22 to 25°C. The administration method was intraperitoneal injection of diquat solution at a toxic dose of 40 mg / kg.
[0051] Treatment methods: 1) Hemoperfusion and hemodiafiltration, each treatment lasts 2 hours, and the treatment is performed 3 times.
[0052] 2) Continuous renal replacement therapy (CRRT) was performed using a continuous blood purification device, with each treatment lasting 8 hours and 2 treatments.
[0053] The experiment set up a blank group (no treatment was used, and the final outcome was death), a control group (equipment alone treatment group, which was conventional treatment) and an experimental group (ultraviolet combined with equipment treatment group, that is, conventional treatment combined with ultraviolet irradiation treatment); the above treatment interventions began 2 hours after administration, and blood was collected before and after treatment, recorded as Cs and Ce. After blood collection, centrifugation was performed at 3500rpm for 10 minutes, and the supernatant serum sample was taken for blood drug concentration analysis. The poison clearance rate was calculated using the formula "poison clearance rate = (Cs-Ce) / Cs×100%", and the prognosis results were recorded. The results are shown in Table 1.
[0054] Table 1:
[0055]
[0056]
[0057] It can be seen from Table 1 that the toxin clearance rate of ultraviolet combined with blood purification treatment is significantly higher than that of single blood purification treatment. The combined treatment has a good detoxification effect and can improve the prognosis.
[0058] Example 6
[0059] Similar to Example 5, hemoperfusion combined with continuous veno-venous hemofiltration (HP+CVVH) was used to treat paraquat-infected Landrace pigs. The paraquat clearance rate was 53.5% after 8 hours of single treatment, and the paraquat clearance rate was 82.1% after 8 hours of combined ultraviolet light irradiation treatment, which was better than the conventional single blood purification method.
[0060] Comparative Example 1
[0061] Using natural light, light sources with wavelengths of 365nm, 310nm, 254nm and 190nm to irradiate other types of pesticides in vitro, including glyphosate, glufosinate, lufenuron, cypermethrin and other non-bipyridine pesticides (non-diquat-similar structures), cannot achieve ultraviolet light degradation and cannot achieve the purpose described in the patent of this invention.
Claims
1. Application of ultraviolet light in the detoxification of bipyridine poisons.
2. The use of ultraviolet light in the detoxification of bipyridine poisons according to claim 1, characterized in that: After acute poisoning, the plasma / blood is irradiated with ultraviolet light of a specific wavelength in an in vitro environment while using a blood purification device.
3. The use of ultraviolet light in the detoxification of bipyridine poisons according to claim 2, characterized in that: The blood purification device is selected from hemodialysis, hemofiltration, hemoperfusion, continuous blood purification equipment, plasma exchange, and immunoadsorption equipment.
4. The use of ultraviolet light in the detoxification of bipyridine poisons according to claim 2, characterized in that: Before irradiating the plasma with ultraviolet light, a photocatalyst is added to the plasma.
5. The use of ultraviolet light in the detoxification of bipyridine poisons according to claim 1, characterized in that: After acute poisoning, ultraviolet light of a specific wavelength is directly irradiated to the epidermis.
6. The use of ultraviolet light in the detoxification of bipyridine poisons according to claim 1 or 5, characterized in that: The ultraviolet light wavelength range is less than 310 nm.
7. The use of ultraviolet light in the detoxification of bipyridine poisons according to claim 6, characterized in that: The wavelength range of the ultraviolet light is 190-310 nm.
8. The use of ultraviolet light in the detoxification of bipyridine poisons according to claim 5, characterized in that: The single ultraviolet light irradiation time is less than 4 hours.
9. The use of ultraviolet light in detoxification of diquat and paraquat according to claim 5, characterized in that: Before ultraviolet light irradiation, the patient first supplements common vitamins or applies a photocatalyst on the skin surface, or both supplements common vitamins and applies a photocatalyst.
10. The use of ultraviolet light in the detoxification of bipyridine poisons according to claim 1, characterized in that: The bipyridine poison is diquat or paraquat.