A traditional Chinese medicine composition for the treatment or prevention of sepsis

Abstract

This invention relates to the field of medicine, specifically to a traditional Chinese medicine composition for treating or preventing sepsis. The composition contains the following herbs in parts by weight: 5-25 parts dandelion, 5-15 parts ligusticum, 4-20 parts notoginseng, 5-15 parts cinnamon twig, 4-15 parts aster, 3-10 parts *Rhodiola rosea*, 8-25 parts prunella vulgaris, 5-18 parts yangqi stone, 4-15 parts epimedium, 1-2.5 parts tripterygium wilfordii, and 6-20 parts *Piper kadsura*. Animal experiments have confirmed that the traditional Chinese medicine composition of this invention can reduce microglia-mediated neuroinflammation, decrease the expression of inflammatory factors such as TM and IL-6, and reduce neuronal damage. It has an inhibitory effect on the expression of IL-6 and HMGB1 in macrophages during sepsis, and has achieved significant results in clinical use.

Description

Technical Field

[0001] This invention relates to the field of medicine, specifically to a traditional Chinese medicine composition for the treatment or prevention of sepsis. Technical Background Sepsis is a severe infectious disease, usually caused by bacteria, viruses, or other microorganisms, leading to a systemic inflammatory response, or systemic inflammatory response syndrome (SIRS). It is characterized by the release of inflammatory mediators resulting in systemic inflammation, multiple organ dysfunction, and tissue damage. Sepsis can be caused by bacteria, fungi, viruses, or parasites, and typically presents with symptoms such as fever, tachycardia, tachypnea, and abnormal white blood cell count. It is a fatal organ dysfunction caused by a dysregulation of the host's response to infection, and its severe nature and high mortality rate are the leading causes of death in critically ill patients. For many years, antibiotics, antiviral drugs, and vasopressors have been used in the traditional treatment of sepsis, but there are still insufficient specific drugs targeting the pathogenesis of sepsis to be available in clinical practice. The pathogenesis of sepsis involves the host's immune system's response to infection. When the body is infected with pathogens, the immune system releases inflammatory mediators, such as cytokines and other inflammatory mediators, in an attempt to eliminate the pathogens. However, in some cases, the immune system's response may be overactivated, leading to a systemic inflammatory response (SIRS), which can then develop into sepsis.

[0002] How to promptly correct the systemic inflammatory response, coagulation dysfunction, and immune dysregulation during the development of sepsis, restore the body's pro-inflammatory-anti-inflammatory dynamic balance as early as possible, and effectively improve patient prognosis has become a crucial issue that urgently needs to be addressed in the research and development of drugs for the treatment of sepsis. Currently, the most common treatment is drug therapy, such as antibiotics: for sepsis patients, early use of appropriate antibiotics is one of the key treatment measures. Antibiotics should be selected based on the susceptibility of the pathogen and administered to the patient as soon as possible while controlling the infection. Vasoactive drugs: including vasoconstrictors and vasodilators, are used to maintain stable blood pressure and improve tissue perfusion and oxygenation. Glucocorticoids: in some specific situations, such as when antibiotic treatment is ineffective, glucocorticoids may be used to modulate the immune response. Other supportive treatments: including fluid resuscitation, mechanical ventilation, and renal replacement therapy, are used to support the patient's organ function.

[0003] The above-mentioned drugs have significant side effects, and serious drug resistance can develop after a period of use. Summary of the Invention

[0004] To address the above deficiencies, the technical problem solved by this invention is to provide a traditional Chinese medicine composition for sepsis, thereby solving the problem of unsatisfactory treatment effects and poor therapeutic outcomes in the prior art for septic brain injury.

[0005] To solve the technical problems of the invention, the present invention provides the following technical solution: This invention provides a traditional Chinese medicine composition for sepsis, which, according to the weight parts, consists of the following traditional Chinese medicines: 5-25 parts by weight of dandelion, 5-15 parts by weight of ligusticum striatum, 4-20 parts by weight of notoginseng, 5-15 parts by weight of cinnamon twig, 4-15 parts by weight of aster, 3-10 parts by weight of jujube, 8-25 parts by weight of prunella vulgaris, 5-18 parts by weight of yangqi stone, 4-15 parts by weight of epimedium, 1-2.5 parts by weight of triptolide, and 6-20 parts by weight of piper kadsura.

[0006] Furthermore, according to the weight parts, the traditional Chinese medicine composition consists of the following traditional Chinese medicines: 5 parts by weight of dandelion, 5 parts by weight of ligusticum, 4 parts by weight of notoginseng, 5 parts by weight of cinnamon twig, 4 parts by weight of aster, 3 parts by weight of monthly jujube, 8 parts by weight of prunella vulgaris, 5 parts by weight of yangqi stone, 4 parts by weight of epimedium, 1 part by weight of tripterygium wilfordii, and 6 parts by weight of piper kadsura.

[0007] Furthermore, according to the weight parts, the traditional Chinese medicine composition consists of the following traditional Chinese medicines: 25 parts by weight of dandelion, 15 parts by weight of ligusticum, 20 parts by weight of notoginseng, 15 parts by weight of cinnamon twig, 15 parts by weight of aster, 10 parts by weight of jujube, 25 parts by weight of prunella vulgaris, 18 parts by weight of yangqi stone, 15 parts by weight of epimedium, 2.5 parts by weight of tripterygium wilfordii, and 20 parts by weight of piper kadsura.

[0008] Furthermore, according to the weight parts, the traditional Chinese medicine composition consists of the following traditional Chinese medicines: 15 parts by weight of dandelion, 10 parts by weight of ligusticum, 9 parts by weight of notoginseng, 10 parts by weight of cinnamon twig, 10 parts by weight of aster, 6 parts by weight of monthly jujube, 15 parts by weight of prunella vulgaris, 9 parts by weight of yangqi stone, 10 parts by weight of epimedium, 1.5 parts by weight of tripterygium wilfordii, and 12 parts by weight of piper kadsura.

[0009] A second objective of this invention is to provide a pharmaceutical preparation comprising the traditional Chinese medicine composition described herein. Further, the pharmaceutical preparation may be one of the following: decoction, compound preparation, granules, pills, tablets, capsules, or powder; preferably, the pharmaceutical preparation is selected from decoctions.

[0010] The sepsis mentioned includes brain, epilepsy, and central nervous system diseases caused by septic encephalopathy.

[0011] Compared with existing technologies, the beneficial effects of the technology are: Animal experiments have confirmed that the traditional Chinese medicine composition of this invention can reduce microglial-mediated neuroinflammation, decrease the expression of inflammatory factors such as TM and IL-6, and reduce neuronal damage. It exhibits a stronger inhibitory effect on the expression of IL-6 and HMGB1 in macrophages during sepsis. Experiments of this invention demonstrate that the drug composition has a stronger therapeutic effect on sepsis. In clinical application, by continuously adjusting the types and amounts of the prescription, a better therapeutic effect can ultimately be achieved. Attached Figure Description

[0012] Figure 1 The effects of the blank group, the model group, and each example group on the expression level of CCR2.

[0013] Figure 2 The protective effects of the blank group, model group, and each embodiment group on reducing neuronal inflammatory damage.

[0014] Figure 3 Effects of the blank group, model group, and each example group on the release level of IL-6 in rat peritoneal macrophages.

[0015] Figure 4 Effects of the blank group, model group, and each example group on the release level of HMGB1 in rat peritoneal macrophages.

[0016] Figure 5 Effects of the blank group, model group, and each example group on the release level of rat peritoneal macrophages™.

[0017] Figure 6 Effects of the blank group, model group, and each example group on IL-6 expression in CLP septic rats.

[0018] Figure 7 Effects of the blank group, model group, and each example group on CLP-induced TM release in septic rats. Detailed Implementation

[0019] The present invention will be further described below with reference to specific embodiments to provide a better understanding of the invention.

[0020] Example 1: A traditional Chinese medicine composition for treating sepsis and its preparation method Dandelion 5g, Ligusticum striatum 5g, Panax notoginseng 4g, Cinnamon twig 5g, Aster tataricus 4g, Rhododendron simsii 3g, Prunella vulgaris 8g, Yangqi stone 5g, Epimedium 4g, Tripterygium wilfordii 1g, Piper kadsura 6g Preparation method: Take the above-mentioned drugs, decoct them in water for 15 minutes, filter, collect the filtrate, and obtain the filtrate; continue to decoct the residue in water for 10 minutes, filter, collect the filtrate twice, concentrate it at 60-70℃ to a relative density of 1.12, let it stand, and take the supernatant to obtain the decoction.

[0021] Example 2: A traditional Chinese medicine composition for treating sepsis and its preparation method Dandelion 25g, Ligusticum striatum 15g, Panax notoginseng 20g, Cinnamon twig 15g, Aster tataricus 15g, Persian berry 10g, Prunella vulgaris 25g, Yangqi stone 18g, Epimedium 15g, Tripterygium wilfordii 2.5g, Piper kadsura 20g Preparation method: Take the above-mentioned drugs, decoct them in water for 35 minutes, filter, collect the filtrate, and obtain the filtrate; continue to decoct the residue in water for 20 minutes, filter, collect the filtrate twice, concentrate it at 60-70℃ to a relative density of 1.17, let it stand, and take the supernatant to obtain the decoction.

[0022] Example 3: A traditional Chinese medicine composition for treating sepsis and its preparation method Dandelion 15g, Ligusticum striatum 10g, Panax notoginseng 9g, Cinnamon twig 10g, Aster tataricus 10g, Persian sage 6g, Prunella vulgaris 15g, Yangqi stone 9g, Epimedium 10g, Tripterygium wilfordii 1.5g, Piper kadsura 12g Preparation method: Take the above-mentioned drugs, decoct them in water for 25 minutes, filter, collect the filtrate, and obtain the filtrate; add water to the residue and decoct for another 15 minutes, filter, collect the filtrate twice, concentrate it at 60-70℃ to a relative density of 1.15, let it stand, and take the supernatant to obtain the decoction.

[0023] Comparative Example 1: A traditional Chinese medicine composition for treating sepsis and its preparation method Safflower 15g, Red peony root 10g, Panax notoginseng 9g, Cinnamon twig 10g, Aster tataricus 10g, Perennial safflower 6g, Prunella vulgaris 15g, Yangqi stone 9g, Epimedium 10g, Tripterygium wilfordii 1.5g, Piper kadsura 12g Preparation method: Take the above-mentioned drugs, decoct them in water for 25 minutes, filter, collect the filtrate, and obtain the filtrate; add water to the residue and decoct for another 15 minutes, filter, collect the filtrate twice, concentrate it at 60-70℃ to a relative density of 1.15, let it stand, and take the supernatant to obtain the decoction.

[0024] Comparative Example 2: A traditional Chinese medicine composition for treating sepsis and its preparation method Panax notoginseng 9g, Cinnamon twig 10g, Aster tataricus 10g, Hedyotis diffusa 6g, Prunella vulgaris 15g, Yangqi stone 9g, Epimedium brevicornu 10g, Tripterygium wilfordii 1.5g, Piper kadsura 12g Preparation method: Take the above-mentioned drugs, decoct them in water for 25 minutes, filter, collect the filtrate, and obtain the filtrate; continue to decoct the residue in water for 15 minutes, filter, collect the filtrate twice, concentrate it at 60-70℃ to a relative density of 1.10, let it stand, and take the supernatant to obtain the decoction.

[0025] Comparative Example 3: A traditional Chinese medicine composition for treating sepsis and its preparation method Dandelion 35g, Ligusticum striatum 3g, Panax notoginseng 19g, Cinnamon twig 30g, Prunella vulgaris 5g, Yangqi stone 1g, Epimedium brevicornu 3g, Tripterygium wilfordii 0.5g, Piper kadsura vine 5g Preparation method: Take the above-mentioned drugs, decoct them in water for 25 minutes, filter, collect the filtrate, and obtain the filtrate; add water to the residue and decoct for another 15 minutes, filter, collect the filtrate twice, concentrate it at 60-70℃ to a relative density of 1.15, let it stand, and take the supernatant to obtain the decoction.

[0026] Comparative Example 4: A traditional Chinese medicine composition for treating sepsis and its preparation method Dandelion 15g, Ligusticum striatum 10g, Panax notoginseng 9g, Cinnamon twig 10g, Aster tataricus 10g, Persian sage 6g, Prunella vulgaris 15g, Yangqi stone 9g, Epimedium 10g, Tripterygium wilfordii 1.5g, Piper kadsura 12g Preparation method: Take the above-mentioned drugs, decoct them in water for 25 minutes, filter, collect the filtrate, and obtain the filtrate; add water to the residue and decoct for another 15 minutes, filter, collect the filtrate twice, concentrate it at 60-70℃ to a relative density of 1.15, let it stand, and take the supernatant to obtain the decoction.

[0027] Verification Example 1: CCR2 reduces microglia-mediated neuroinflammation and neuronal damage after septic encephalopathy. Seventy clean-grade SD rats (half male and half female), weighing 180–220g, were selected for this experiment based on their weight gain, diet, and activity during the adaptation period. They were divided into seven groups of 10 rats each using a weight-based grouping method: blank group, model group, Example 3 group, and comparative groups 1–4, with half male and half female.

[0028] 1. Cell model construction BV2 microglia were cultured in DMEM medium with 10% FBS and 1% penicillin-streptomycin at 37°C and 5% CO2. LPS was used to induce an inflammatory phenotype in the microglia.

[0029] 2. Cell Experiment Grouping BV2 microglia were seeded into 6-well plates and divided into a blank group, a model group, and groups of Examples 3, 1, 2, 3, and 4. TAX (taraxasterol) was administered to the blank group. BV2 cells in the blank group were cultured normally without treatment. The model group was treated with LPS. Groups of Examples 3, 1, 2, 3, and 4 were treated with supernatant for 36 hours.

[0030] 3. Neuronal damage detection Neuronal damage was assessed using the CCK8 assay to detect cell viability.

[0031] 4. CCR2 detection After centrifuging and collecting BV-2 cells, proteins were extracted using a kit and their concentrations were determined. CCR2 expression was detected by Western blotting, the bands were visualized using an imaging system, and quantitative analysis was performed using ImageJ software.

[0032] 5. Data Statistical Analysis All statistical analyses were performed using GraPhpadPrism 9.0 software with blinding. Data were expressed as mean ± SD within the body and as mean ± SEM in vitro. All data were analyzed using one-way ANOVA for multiple comparisons, Student's t-tests, and nonparametric tests. A p-value < 0.05 was considered statistically significant.

[0033] 6. Results Analysis Figure 1 It can be seen that the effect of CCR2 expression level is significant. The linear relationship between the blank group and the model group is extremely significant, and all example groups effectively reduce CCR2 expression level. Example 3 group shows significant differences compared with the comparative groups, indicating that the formulation and dosage of the present invention are superior to the prior art.

[0034] Figure 2 As can be seen, the effects of each group in the embodiments of the present invention on reducing neuronal inflammatory damage were detected by constructing a BV2 microglia inflammatory phenotype and incubating HT22 hippocampal neurons with the supernatant. Both the Example 3 group and the comparative groups effectively increased neuronal survival, with the Example 3 group showing a significant difference compared to the comparative groups.

[0035] Verification Example 2: Evaluation of the effect of the drug of the present invention on IL-6 release from rat peritoneal macrophages under endotoxin LPS stimulation. 1. Experimental Materials Seventy clean-grade male SD rats, weighing 180–220g, were selected for this experiment based on their weight gain, diet, and activity during the adaptation period. They were then divided into seven groups of ten rats each using a weight-based grouping method: a control group, a model group, Example 3 group, and Comparative Examples 1–4 groups. RPMI-1640 medium, 24-well plates, and an IL-6 ELISA kit were used.

[0036] 2. Experimental Methods The following method was used to isolate peritoneal macrophages from male SD rats: Male SD rats were fasted for 12 hours before surgery. After anesthesia, the peritoneal cavity was opened, and 10 mL of pre-cooled PBS was injected. The abdominal wall was gently massaged with fingers to allow the fluid to flow within the peritoneal cavity. The fluid from the peritoneal cavity was aspirated and injected into a sterile tube, which was then rinsed once with 10 mL of pre-cooled PBS, following the same procedure. 250 g of the combined rinsing fluid was centrifuged at 4°C for 10 min, and the supernatant was discarded. 2 mL of erythrocyte lysis buffer was added to dissolve the erythrocytes, and the cells were gently shaken twice for 5 seconds each time. After standing for 5 min, 4 mL of L-Hanks solution was added to terminate the reaction. The cells were centrifuged again using the same method, and the supernatant was discarded. The precipitate was washed with culture medium, and the cells were resuspended to prepare 2 × 10⁶ cells / mL. 6 / mL cell suspension. The cell suspension was seeded into 24-well plates and incubated in a cell culture incubator at 37°C and 5% CO2. Six parallel wells were used per group. After 12h and 24h of culture, the supernatant was collected, and the cytokine content was determined by a one-step sandwich enzyme-linked immunosorbent assay (ELISA) with double antibodies.

[0037] The experiment was divided into a blank control group, a model group, Example 3 group, and Comparative Examples 1-4 groups. The treatment methods for each group were as follows: Cells in each group were cultured overnight at 37°C in a 5% CO2 incubator. The blank control group and model group were given the corresponding volume of culture medium, while Example 3 group and Comparative Examples 1-4 groups were given the corresponding volume of supernatant. After incubation for 1 hour, the blank control group was not given LPS, while the model group, Example 3 group, and Comparative Examples 1-4 groups were stimulated with LPS (75 ng / mL). At 12 and 24 hours, 0.5 mL of cell culture supernatant was collected from each group and stored at -20°C for subsequent cytokine detection.

[0038] Figure 3 The results showed that, compared with the model group, both the blank group and each example group significantly reduced the release level of IL-6 in rat peritoneal macrophages at 12h and 24h, indicating that each example group had a good inhibitory effect on early inflammatory factors in the sepsis cell model. At 12h, the comparison showed that the Example 3 group was significantly different from the Comparative Examples 1-4 groups, and at 24h, the comparison showed that the Example 3 group was extremely significantly different from the Comparative Examples 1-4 groups (P<0.01).

[0039] Verification Example 3: Evaluation of the effect of the drug of the present invention on the release of HMGB1 from rat peritoneal macrophages under endotoxin LPS stimulation. 1. Experimental Materials Seventy male clean-grade SD rats (180–220g) were selected for this experiment based on their weight gain, diet, and activity during the adaptation period. They were then divided into seven groups of ten rats each using a weight-based grouping method: a control group, a model group, Example 3 group, and Comparative Examples 1–4 groups. RPMI-1640 medium, 24-well plates, and endotoxin (LPS) and IL-6 ELISA kits were used.

[0040] 2. Experimental Methods The following method was used to isolate peritoneal macrophages from male SD rats: Male SD rats were fasted for 12 hours before surgery. After anesthesia, the peritoneal cavity was opened, and 10 mL of pre-cooled PBS was injected. The abdominal wall was gently massaged with fingers to allow the fluid to flow within the peritoneal cavity. The fluid from the peritoneal cavity was aspirated and injected into a sterile tube, which was then rinsed once with 10 mL of pre-cooled PBS, following the same procedure. 250 g of the combined rinsing fluid was centrifuged at 4°C for 10 min, and the supernatant was discarded. 2 mL of erythrocyte lysis buffer was added to dissolve the erythrocytes, and the cells were gently shaken twice for 5 seconds each time. After standing for 5 min, 4 mL of L-Hanks solution was added to terminate the reaction. The cells were centrifuged again using the same method, and the supernatant was discarded. The precipitate was washed with culture medium, and the cells were resuspended to prepare 2 × 10⁶ cells / mL. 6 / mL cell suspension. The cell suspension was seeded into 24-well plates and cultured in a cell culture incubator at 37°C and 5% CO2. Six parallel wells were used per group. After culturing for 48 h and 72 h, the supernatant was collected, and the cytokine content was determined by a one-step sandwich enzyme-linked immunosorbent assay (ELISA) with double antibodies.

[0041] The experiment was divided into a blank group (control), a model group, Example 3 group, and Comparative Examples 1-4 groups. The treatment methods for each group were as follows: After the cells in each group were cultured overnight in a cell culture incubator at 37°C and 5% CO2, the blank group (control) and the model group were given the corresponding volume of culture medium, while Example 3 group and Comparative Examples 1-4 groups were given the same volume of the corresponding concentration of drug solution. After incubation in the incubator for 1 hour, the blank group (control) was not given LPS, while the model group, Example 3 group, and Comparative Examples 1-4 groups were given LPS (75 ng / mL) for stimulation. After 48 hours and 72 hours, 0.5 mL of cell culture supernatant was collected from each group and stored in a -20°C refrigerator for centralized detection of corresponding cytokines.

[0042] 3. Experimental Results Figure 4 The results showed that, compared with the model group, both the blank group and each example group significantly reduced the release level of HMGB1 from rat peritoneal macrophages at 48h and 72h, indicating that each example group had a good inhibitory effect on early inflammatory factors in the sepsis cell model. At 48h and 72h, the comparison revealed that the Example 3 group had a highly significant difference compared with the Comparative Examples 1-4 (P<0.01).

[0043] Verification Example 4: Evaluation of the effect of the drug of the present invention on the release of TM from rat abdominal aortic endothelial cells under endotoxin LPS stimulation. 1. Experimental Materials Seventy male clean-grade SD rats (180–220 g) were selected for this experiment based on their weight gain, diet, and activity during the adaptation period. They were then divided into seven groups of ten rats each using a weight-based grouping method: blank group, model group, Example 3 group, and comparative groups 1–4. ECM culture medium, 24-well plates, and endotoxin (LPS) and tissue factor (TM) ELISA kits were used.

[0044] 2. Experimental Methods After euthanizing rats by cervical dislocation, they were immersed in 75% ethanol for 5 minutes. The thoracic and abdominal cavities were opened layer by layer to fully expose the thoracic and abdominal aortas. The surrounding tissues were separated, and the aorta was separated from the proximal end to the branch of the common iliac artery. The rats were placed in a culture dish containing PBS, and the adipose and fibrous tissues of the adventitia of the blood vessels were aseptically dissected. The blood vessel lumen was then rinsed with PBS. Cut the aorta into small pieces of approximately 1.5 mm × 1.5 mm and place them in 6 mL of 0.25% type IV collagenase. Digest at 37°C for 15 min, shaking every 5 min. Carefully aspirate the digestive fluid, retaining the tissue pieces. Add 6 mL of 1.0% neutral protease and digest at 37°C for 15 min, shaking every 5 min. Aspirate the digestive fluid, add 10 mL of ECM, and repeatedly pipette. Centrifuge at 1000 rpm for 10 min, discarding the culture medium and digestive fluid, retaining the fragments. Spread the tissue pieces evenly on the bottom of a 10 cm culture dish, invert it in a 37°C oven for 2 h to allow the tissue pieces to adhere firmly. Add an appropriate amount of ECM, ensuring it submerges the tissue pieces. Incubate at 37°C in a 5% CO2 saturated humidity incubator, changing the culture medium every 3 days. After about 7 days, endothelial cells can be seen crawling out from the edge of the tissue block and gradually extending outward, appearing as flat, short spindle-shaped or polygonal cells. Remove the tissue block, digest it with 0.25% trypsin, and passage it in a 25cm2 culture flask at a ratio of 1:3. Use the 3rd to 4th generation cells for experiments.

[0045] Cells were cultured according to the above-described method for culturing rat abdominal aortic endothelial cells, and a cell suspension was prepared at 1.2 × 10⁻⁶. 5 Cells were seeded at / mL and the cell suspension was seeded into 24-well plates and cultured at 37°C. After about 12 hours, the model group, Example 3 group and Comparative Examples 1-4 groups were stimulated with LPS. After 1 hour, different drug solutions were administered for intervention. The supernatant was collected at 24 hours, 48 ​​hours and 72 hours after stimulation.

[0046] The experiment was divided into a blank group (control), a model group, Example 3 group, and Comparative Examples 1-4 groups. The treatment methods for each group were as follows: After the cells in each group were cultured overnight in a cell culture incubator at 37°C and 5% CO2, the blank group (control) and the model group were given the corresponding volume of culture medium, while Example 3 group and Comparative Examples 1-4 groups were given the same volume of the corresponding concentration of drug solution. After incubation in the incubator for 1 hour, the blank group (control) was not given LPS, while the model group, Example 3 group, and Comparative Examples 1-4 groups were given LPS (75 ng / mL) for stimulation. After 48 hours and 72 hours, 0.5 mL of cell culture supernatant was collected from each group and stored in a -20°C refrigerator for centralized detection of corresponding cytokines.

[0047] 3. Experimental Results Figure 5 The results showed that, compared with the model group, both the blank group and each example group significantly reduced the release level of TM from rat peritoneal macrophages at 48h and 72h, indicating that each example group had a good inhibitory effect on early inflammatory factors in the sepsis cell model. At 48h and 72h, comparison revealed that the Example 3 group had a highly significant difference compared with Comparative Examples 1-4 (P<0.01). This further demonstrates that the composition and dosage of Example 3 of the present invention can effectively promote the restoration of normal coagulation function.

[0048] Verification Example 5: Evaluation of the effect of the drug of the present invention on IL-6 expression in CLP-induced septic rats. 1. Experimental Materials Male clean-grade SD rats (180–220 g) were acclimatized for one week. Seventy animals were selected for this experiment based on their weight gain, diet, and activity during the acclimatization period. They were divided into seven groups of 10 animals each using a weight-based grouping method: blank group, model group, Example 3 group, and comparative groups 1–4. ELISA kits were used.

[0049] 2. Experimental Procedure The CLP modeling process is as follows: Rats were anesthetized by intramuscular injection of a mixture of ketamine injection and sedative injection at a volume ratio of 2:1. A sepsis animal model was established using CLP. The junction of the cecum and ileum was ligated, and the cecum was punctured twice with an 18-gauge needle to form an intestinal fistula. Two drainage strips (0.5cm × 2.0cm) were left in place to prevent the needle holes from healing. The skin was then sutured layer by layer. Immediately after the operation, 10mL of physiological saline was injected subcutaneously for resuscitation.

[0050] 3. Dosage Each rat was administered the drug via gavage at a dose of 200g. In the example, the dosage for each group was calculated as 0.27g / kg of raw drug, once daily, 5ml each time. The model group and the control group were injected with physiological saline via the tail vein at the corresponding time, once daily, 5ml each time.

[0051] 4. Blood collection and testing 48h and 72h after CLP, 3mL of blood was aseptically collected from the abdominal aorta of each group of animals after anesthesia, and the plasma IL-6 content was detected by ELISA.

[0052] 5. Experimental Results Figure 6 As can be seen, compared with the model group, all example groups significantly reduced the expression of IL-6 in CLP septic rats, suggesting a significant inhibitory effect on the early inflammatory response in the septic rat model. The expression of TM in the model group (8h, 16h, and 24h post-surgery) was significantly higher than that in the control group (p<0.05), and gradually increased with the extension of post-operative time. The expression of IL-6 in Example 3 and Comparative Examples 1-4 was significantly lower than that in the model group (p<0.05). These findings suggest that, compared with the model group, all example groups significantly reduced the release of IL-6 in CLP septic rats, and that these groups significantly inhibited the release of coagulation factors and improved the hypercoagulable state in the septic rat model. Furthermore, Example 3 showed a significant difference compared with Comparative Examples 1-4 (48h and 72h post-surgery, P<0.05).

[0053] Verification Example 6: Evaluation of the effect of the drug of the present invention on CLP-induced TM release in CLP-induced septic rats 1. Experimental Materials Male clean-grade SD rats (180–220 g) were acclimatized for one week. Seventy animals were selected for this experiment based on their weight gain, diet, and activity during the acclimatization period. They were divided into seven groups of 10 animals each using a weight-based grouping method: blank group, model group, Example 3 group, and comparative groups 1–4. ELISA kits were used.

[0054] 2. Experimental Procedure The CLP modeling process is as follows: Rats were anesthetized by intramuscular injection of a mixture of ketamine injection and sedative II injection at a volume ratio of 2:1. A sepsis animal model was established using CLP. The junction of the cecum and ileum was ligated, and the cecum was punctured twice with an 18-gauge needle to create an enterocutaneous fistula. Two drainage strips (0.5cm × 2.0cm) were left in place to prevent the needle punctures from healing. The skin was then sutured layer by layer. Immediately after the procedure, 10mL of physiological saline was injected subcutaneously for resuscitation. 3. Dosage Each rat was administered the drug via gavage at a dose of 200g. In the example, the dosage for each group was calculated as 0.27g / kg of raw drug, once daily, 5ml each time. The model group and the control group were injected with physiological saline via the tail vein at the corresponding time, once daily, 5ml each time.

[0055] 4. Blood collection and testing 48h and 72h after CLP, 3mL of blood was aseptically collected from the abdominal aorta of each group of animals after anesthesia, and the plasma TM content was detected by ELISA.

[0056] 5. Experimental Results Figure 7 It can be seen that TM expression was present in monocytes of the control group; the expression of TM in the model group (8h, 16h, 24h, 48h, and 72h post-surgery) was significantly higher than that in the control group (p<0.05), and gradually increased with the extension of post-operative time. The expression of TM in Example 3 and Comparative Examples 1-4 was significantly lower than that in the model group (p<0.05). These findings suggest that, compared with the model group, each example group can significantly reduce the release of TM in CLP-secreting rats, and the group has a significant effect on inhibiting the release of coagulation factors and improving the hypercoagulable state in the sepsis rat model. Furthermore, Example 3 showed a significant difference compared with Comparative Examples 1-4 (8h, 16h, 24h, 48h, and 72h post-surgery, P<0.05).

Claims

1. A traditional Chinese medicine composition for treating sepsis, characterized in that, According to the weight parts, the traditional Chinese medicine composition consists of the following traditional Chinese medicines: 5-25 parts by weight of dandelion, 5-15 parts by weight of ligusticum, 4-20 parts by weight of notoginseng, 5-15 parts by weight of cinnamon twig, 4-15 parts by weight of aster, 3-10 parts by weight of jujube, 8-25 parts by weight of prunella vulgaris, 5-18 parts by weight of yangqi stone, 4-15 parts by weight of epimedium, 1-2.5 parts by weight of tripterygium wilfordii, and 6-20 parts by weight of piper kadsura.

2. The traditional Chinese medicine composition as described in claim 1, characterized in that, According to the weight parts, the traditional Chinese medicine composition consists of the following traditional Chinese medicines: 5 parts by weight of dandelion, 5 parts by weight of ligusticum, 4 parts by weight of notoginseng, 5 parts by weight of cinnamon twig, 4 parts by weight of aster, 3 parts by weight of monthly jujube, 8 parts by weight of prunella vulgaris, 5 parts by weight of yangqi stone, 4 parts by weight of epimedium, 1 part by weight of tripterygium wilfordii, and 6 parts by weight of piper kadsura.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition, by weight, consists of the following herbs: 25 parts dandelion, 15 parts ligusticum, 20 parts notoginseng, 15 parts cinnamon twig, 15 parts aster, 10 parts perennial rhododendron, 25 parts prunella vulgaris, 18 parts yangqi stone, 15 parts epimedium, 2.5 parts tripterygium wilfordii, and 20 parts piper kadsura.

4. The traditional Chinese medicine composition according to claim 1, characterized in that, According to the weight parts, the traditional Chinese medicine composition consists of the following traditional Chinese medicines: 15 parts by weight of dandelion, 10 parts by weight of ligusticum, 9 parts by weight of notoginseng, 10 parts by weight of cinnamon twig, 10 parts by weight of aster, 6 parts by weight of jujube, 15 parts by weight of prunella vulgaris, 9 parts by weight of yangqi stone, 10 parts by weight of epimedium, 1.5 parts by weight of tripterygium wilfordii, and 12 parts by weight of piper kadsura.

5. A pharmaceutical preparation for treating sepsis, characterized in that, The pharmaceutical preparation contains any one of the traditional Chinese medicine compositions described in 1-4.

6. The pharmaceutical formulation as described in claim 5, characterized in that, The pharmaceutical preparation mentioned is one of the following: decoction, mixture, granules, pills, tablets, capsules, or powder.

7. The pharmaceutical formulation as described in claim 5, characterized in that, The pharmaceutical preparation mentioned is selected from decoctions.

8. The traditional Chinese medicine composition according to claim 1, characterized in that, The sepsis mentioned refers to septic encephalopathy, which causes brain, epilepsy, or other central nervous system diseases.

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