Application of Tibetan medicine Wupeng pill compound preparation in relieving acute lung injury caused by sepsis
By using Wupeng Wan in a septic mouse model, the survival rate was significantly improved and the inflammatory factor level was reduced, lung tissue damage was reduced, the problem of lack of treatment measures for septic ALI was solved, and a Chinese medicine was provided Auxiliary products have significant economic and social value.
Patent Information
- Application Number
- CN202411527749.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-30
- Publication Date
- 2025-01-07
AI Technical Summary
The prior art treatment measures for acute lung injury related to sepsis are limited, and the application of traditional Chinese medicine has not been reported in this field. The use of Wupeng Pills depends on clinical experience and lacks effective treatment plans for ALI of sepsis.
Tibetan medicine Wupeng Pills were used to treat acute lung injury caused by sepsis. By treating Wupeng Pills of 1000mg/kg/day in a CLP sepsis mouse model, its survival rate, inflammatory factors and Effects of lung tissue damage.
It significantly improved the survival rate of septic mice, reduced the level of IL-1β in the inflammatory factor in lung tissue, reduced the pathological structure damage of lung tissue, and provided an effective traditional Chinese medicine intervention with economic and social value. .
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Figure CN119258148A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the application field of traditional Chinese medicine, and in particular to the application of a Tibetan medicine Wupeng pill compound preparation in alleviating acute lung injury caused by sepsis. Background Art
[0002] Wupeng Pills are also known as Wuwei Musk Pills. Its Tibetan name is Qiong Aribu. The prescription consists of five Tibetan medicinal materials: 20g of Terminalia chebula (pitted), 5g of costus root, 3g of Tibetan calamus, 10g of black aconite and 1.5g of musk. It is a Tibetan medicine variety included in the "Chinese Pharmacopoeia". The Terminalia chebula in the prescription can astringe the intestines and stop diarrhea, reduce fire and relieve sore throat; costus root can promote qi circulation and relieve pain, strengthen the spleen and reduce swelling; Tibetan calamus can reduce inflammation and relieve pain, resolve phlegm and remove dampness; black aconite can relieve pain and reduce swelling, promote blood circulation and remove blood stasis; musk can promote blood circulation and regulate menstruation, reduce swelling and relieve pain. The five medicines together have the effects of clearing away heat and cooling blood, relieving pain and swelling, and dispelling wind and dampness. It is an ancient Tibetan medicine prescription for treating many diseases such as joint swelling and pain, worm diseases, anthrax, etc., with a very long development history.
[0003] Clinical efficacy observation shows that Wupeng Pills have good anti-inflammatory and analgesic effects. In recent years, the application scope of this prescription has gradually expanded. Relevant literature shows that Wupeng Pills are used in combination with other Tibetan medicines to treat inflammations such as gouty arthritis, chronic gastritis, ulcerative colitis and cystitis. Lv Huiling and others from the School of Medicine of Qinghai University used the xylene-induced mouse ear swelling method, the mouse abdominal capillary permeability method, and the carrageenan-induced rat ankle swelling method to observe the anti-inflammatory effect of Wupeng Pills, and preliminarily concluded that Wupeng Pills have significant anti-inflammatory effects. However, the therapeutic effect of Wupeng Pills on lung injury has not been studied, and it is still unclear whether it can improve the survival rate of septic mice and reduce acute lung injury in sepsis.
[0004] Sepsis refers to a systemic inflammatory response syndrome caused by infection, which is characterized by rapid onset and high mortality. When sepsis occurs, the release and activation of a large number of inflammatory factors and inflammatory mediators often lead to an imbalance of anti-inflammatory and pro-inflammatory factors in the body, impaired immune function, and serious damage to various organs if not controlled in time. Common complications of sepsis include acute lung injury, acute kidney injury, and multiple organ failure. Among them, the lung is the most commonly affected organ when sepsis induces multiple organ dysfunction, and acute lung injury (ALI) is an important cause of death in sepsis patients. According to relevant epidemiological surveys, the incidence of ALI in sepsis patients is 68.2%, and the 90-day mortality rate of patients with ALI is as high as 35.5%.
[0005] At present, clinical treatment measures for sepsis ALI are very limited. In addition to conventional anti-infection and organ function support, the scientific community is working hard to find more effective treatment measures to save the lives of more sepsis patients. At present, the clinical treatment of sepsis widely uses antibiotics, fluid resuscitation, blood purification, mechanical ventilation and multi-organ support, but these treatments are prone to increase bacterial resistance, causing adverse reactions in the body, and significantly reducing the treatment effect. Compared with existing treatment measures, traditional Chinese medicine has the advantages of small side effects and multi-molecule and multi-target effects, and has gradually become an effective complementary alternative therapy. Xuebijing is the only traditional Chinese medicine injection approved for sepsis as an indication, and is mainly used to treat severe patients with sepsis and other combined organ dysfunction.
[0006] Tibetan medicine compound is formulated according to Tibetan medicine theory. Many of the drugs have the effects of anti-inflammatory and antibacterial, clearing away heat and detoxifying, reducing swelling and relieving pain, and expelling wind and dampness. They are used to treat inflammations such as lymph tuberculosis, tonsillitis, bronchitis, and pneumonia. However, there are no reports on the therapeutic effects of Tibetan medicine compound on sepsis and its concurrent acute lung injury (ALI). The use of Wupeng Pills is mainly based on the accumulation of clinical experience. At present, there is no report on the use of Wupeng Pills in the treatment of sepsis-related acute lung injury. Developing it into a traditional Chinese medicine product for sepsis ALI has obvious economic and social value. Summary of the invention
[0007] The purpose of the present invention is to expand the range of diseases treated by the Tibetan medicine Wupeng Pills; at the same time, to accurately locate the Tibetan medicine Wupeng Pills in the prevention and treatment of a new clinical indication, sepsis-related acute lung injury.
[0008] The technical solution of the present invention is as follows:
[0009] Application of Tibetan medicine Wupeng Pills in the preparation of medicines for the treatment of acute lung injury.
[0010] Furthermore, the acute lung injury is acute lung injury caused by sepsis.
[0011] Further, the dosage is 1000 mg (drug) / kg (body weight) / day.
[0012] The beneficial effects of the present invention are:
[0013] In the CLP sepsis mouse model, after treatment with Wupeng Pills, the survival rate of mice in the drug-treated group was significantly improved compared with that in the model group; inflammatory factor detection showed that the level of inflammatory factor IL-1β in the lung tissue of mice in the Wupeng Pills-treated group was significantly reduced; HE staining showed that the pathological structural damage of the lung tissue in the Wupeng Pills-treated group was significantly alleviated. The above results show that Wupeng Pills has the effect of significantly improving sepsis ALI. This compound can provide a Chinese medicine intervention measure with definite efficacy for sepsis ALI, and developing it as an auxiliary Chinese medicine product for sepsis ALI has obvious economic and social value.
[0014] In the application of the present invention, the dosage of Wupeng Pills is a relatively safe dosage (1000 mg / kg / day). In order to evaluate the toxicity of this dosage, we gave a single drug treatment group, and no toxicity was observed at this dosage. BRIEF DESCRIPTION OF THE DRAWINGS
[0015] Figure 1 Effect of Wupeng Pills on the survival rate of CLP sepsis mice;
[0016] Figure 2 Wupeng Pills reduced the level of IL-1β, an inflammatory factor in lung tissue of CLP sepsis mice; Figure 2 A is the mRNA expression level of IL-1β, an inflammatory factor in the lung tissue of mice in each group. Figure 2 B is the expression level of IL-1β protein, an inflammatory factor in the lung tissue of mice in each group. Figure 2 C is the quantitative analysis of the expression level of inflammatory factor IL-1β protein in lung tissue of mice in each group;
[0017] Figure 3 Wupeng Pills alleviate lung tissue damage in CLP sepsis mice (×100) HE staining of lung tissue. DETAILED DESCRIPTION
[0018] The present invention is further explained below with reference to the examples, but the examples do not limit the present invention in any form.
[0019] The Wupeng pills used in the following examples of the present invention were obtained from the Derge Zongsachimei Tibetan Hospital, which were fully ground with a mortar and sieved through an 80-mesh sieve for later use;
[0020] Compound Isatis Root Granules were purchased from Guangzhou Baiyunshan Hutchison Whampoa Chinese Medicine Co., Ltd.;
[0021] ICR mice (male) were purchased from the Center for Comparative Medicine of Yangzhou University, animal license number SCXK (Su) 2022-0009, and were kept in the animal room of the Experimental Animal Center of China Pharmaceutical University for 3 days to adapt to the environment before the experiment began. During the feeding period, they had free access to food and water, and the ambient temperature was controlled at 22 ± 1 ° C, accompanied by 12 h light / dark alternation.
[0022] Example 1 Wupeng Pills improve the survival protection rate of CLP sepsis mice
[0023] 32 mice were randomly divided into four groups, as follows: Group 1: normal control group (normal saline); Group 2: CLP sepsis lung injury model group; Group 3: Wupeng pill administration group (1000mg / kg); Group 4: Isatis root administration group (1000mg / kg). There were 8 mice in each group, and all mice had a normal diet. The mice in the above groups were given normal saline or pre-administration once a day for two consecutive days, and CLP modeling was performed 1 hour after the end of gavage on the second day.
[0024] Cecal ligation operation process: Anesthetize the mouse with 4% chloral hydrate (400 mg / kg). If there is no response when the mouse's limbs are touched with tweezers, the surgery can be performed. Fix the mouse on a foam board, use sterilized surgical scissors to cut the outer skin about 1 to 1.5 cm along the midline of the mouse's abdomen, then cut the endothelium, find the mouse's cecum, and place the cecum outside the abdominal cavity. Use 3-0 sutures to ligate it at three quarters of the distance from the end of the cecum, and then use an 18G puncture needle to puncture the cecum and squeeze out a small amount of contents. Put the ligated and punctured cecum back into the abdominal cavity, and suture the inner and outer skins. The blank group was operated in the same way, but no ligation and puncture were performed. 72 hours after surgery, the survival status of mice in each group was observed. The results are as follows Figure 1 As shown, compared with the model group, the survival rate of septic mice was improved after administration of Wupeng Pills, and the effect was better than that of the Isatis root group.
[0025] Example 2 Wupeng Pills reduce the inflammatory response in the lung tissue of CLP sepsis mice
[0026] The mice were randomly divided into four groups as follows: Group 1: normal control group (normal saline); Group 2: CLP sepsis lung injury model group; Group 3: Wupeng pill administration group (1000 mg / kg); Group 4: Isatis root administration group (1000 mg / kg). All mice had a normal diet. The mice in the above groups were given normal saline or pre-administered once a day for two consecutive days, and CLP modeling was performed 1 hour after the end of gavage on the second day.
[0027] After 48 hours of modeling, the lungs were harvested and protein and mRNA were extracted to detect the levels of inflammatory factors. Figure 2 As shown in the figure, we observed that the level of IL-1β, an inflammatory factor in the lung tissue of mice in the Wupeng Pills group, was significantly lower than that in the CLP model group, with statistically significant differences. The results showed that Wupeng Pills has a lung-protecting effect and can reduce the damage caused by sepsis to the lungs of mice.
[0028] Example 3 Wupeng Pills alleviate pathological damage in lung tissue of septic mice
[0029] The mice were randomly divided into four groups as follows: Group 1: normal control group (normal saline); Group 2: sepsis lung injury model group; Group 3: Wupeng pill administration group (1000 mg / kg); Group 4: Isatis root administration group (1000 mg / kg). All mice had a normal diet. The mice in the above groups were given normal saline or pre-administered once a day for two consecutive days, and CLP modeling was performed 1 hour after the end of gavage on the second day.
[0030] 48 hours after modeling, lung tissue HE staining was performed. Figure 3 As shown in the figure, there was no significant difference in the pathological morphology of the mouse lung tissue between the Wupeng Pills alone administration group and the normal control group, indicating that this dose of Wupeng Pills had no damaging effect on the lung tissue; secondly, we observed that the lung tissue sections of the model group showed obvious alveolar structural destruction, inflammatory cell infiltration, vascular wall thickening, capillary congestion and other inflammatory manifestations. The organ congestion phenomenon in the Wupeng Pills group and the Isatis Radix group was alleviated, and the alveolar structure was protected to a certain extent. The pathological structural damage of the lung tissue of the mice in the Wupeng Pills treatment group was significantly reduced compared with the model group, with statistical differences. The above results show that Wupeng Pills has the effect of protecting the lungs and can reduce the structural damage caused by sepsis to the lung tissue of mice.
[0031] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.
Claims
1. Application of Tibetan medicine Wupeng Pills in the preparation of drugs for the treatment of acute lung injury.
2. The use according to claim 1, characterized in that: The acute lung injury is acute lung injury caused by sepsis.
3. The use according to claim 1, characterized in that: The dosage is 1000mg / kg / day.