Traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis and a preparation method and application thereof.The prescription of the traditional Chinese medicine composition comprises 10 + / -1 parts of immature bitter oranges, 10 + / -1 parts of mangnolia officinalis, 20 + / -1 parts of radix aucklandiae, 10 + / -1 parts of radix paeoniae rubra, 10 + / -1 parts of peach kernels, 10 + / -1 parts of salvia miltiorrhiza, 10 + / -1 parts of honeysuckle, 10 + / -1 parts of scutellaria baicalensis, 8 + / -1 parts of fructus cannabis, 10 + / -1 parts of rheum officinale and 15 + / -1 parts of mirabilite. The traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis can treat qi stagnation type intestinal obstruction (simple intestinal obstruction), heat accumulation type intestinal obstruction (twisted narrow intestinal obstruction) and blood stasis type intestinal obstruction (intestinal adhesion or neoplastic intestinal obstruction), the treatment range of Dachengqi decoction is expanded, and the curative effect is remarkable; the traditional Chinese medicine can also treat edema type acute pancreatitis.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis, a preparation method and an application thereof. Background Art

[0002] Intestinal Obstruction (IO) is one of the common acute abdominal diseases in surgery, mainly referring to the sudden stagnation of the contents in the intestine, which causes complex pathophysiological changes in the intestine and even the whole body. The main etiological types are idiopathic pseudo-intestinal obstruction, mechanical, dynamic, and vascular intestinal obstruction. Clinically, it is manifested as abdominal pain, abdominal distension, vomiting, and cessation of defecation and flatulence, with acute abdominal pain as its common symptom. Among them, adhesive intestinal obstruction (AIO) caused by intra-abdominal adhesions (including surgery, inflammation, etc.) is the most common. The treatment of AIO has become a difficult problem in current surgery, and there is no exact method at home and abroad to prevent its occurrence.

[0003] Currently, the western medicine treatment of intestinal obstruction mainly includes non-surgical treatment and surgical treatment. Non-surgical treatment includes: gastrointestinal decompression (fasting and water deprivation), maintaining water, electrolyte and acid-base balance, anti-infection, and applying some drugs for moistening the intestines and relieving constipation. The non-surgical treatment of western medicine has a slow curative effect and a long course of disease, with certain limitations. Surgical treatment will also cause new adhesions and aggravate the symptoms. Surgery includes: laparoscopic surgery, intestinal evacuation surgery, laparotomy for adhesiolysis or intestinal resection and anastomosis surgery, etc. However, the human intestine is complex, the exploration range is wide, and it is easier to miss inspection. With the prolongation of the operation time, the risk of postoperative infection increases, and even new adhesions occur, increasing the pain of patients. Therefore, the clinical treatment of AIO with western medicine has become one of the difficult problems.

[0004] Traditional medicine believes that intestinal obstruction belongs to the category of "intestinal knot" in traditional Chinese medicine. The main pathogenesis: the qi of the fu-organs is not smooth, and the qi mechanism is stagnated. The main causes of the disease are various reasons such as improper diet, cold pathogen stagnation, heat pathogen stagnation, qi and blood stasis, and dry feces accumulation in the large intestine, which lead to abnormal conduction function of the large intestine. Clinically, the four typical symptoms are pain, vomiting, distension, and constipation. The clinical treatment principle of traditional Chinese medicine is "the six fu-organs function by being unobstructed", "if it is unobstructed, there is no pain; if it is unobstructed, there is pain", and usually the Major Decoction for Purgation in Treatise on Febrile Diseases written by Zhang Zhongjing, the sage of medicine, is used for treatment, and the curative effect is remarkable.

[0005] However, the Major Decoction for Purgation can usually only treat heat-type intestinal obstruction (strangulated intestinal obstruction), with certain limitations.

[0006] Based on this, the present invention is proposed. Summary of the Invention

[0007] The object of the present invention is to provide a traditional Chinese medicine composition, a preparation method and an application for treating intestinal obstruction and acute pancreatitis, so as to solve the above problems.

[0008] In the first aspect, a traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis, comprising the following traditional Chinese medicine raw materials in parts by mass:

[0009] Fructus Aurantii Immaturus 10±1 parts, Magnolia officinalis 10±1 parts, Aucklandia lappa 20±1 parts, Radix Paeoniae Rubra 10±1 parts, Prunus persica 10±1 parts, Salvia miltiorrhiza 10±1 parts, Lonicera japonica 10±1 parts, Scutellaria baicalensis 10±1 parts, Cannabis sativa seed 8±1 parts, Rheum palmatum 10±1 parts, Natrii Sulfas 15±1 parts.

[0010] Further improvement, the traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis, comprising the following traditional Chinese medicine raw materials in parts by mass:

[0011] Fructus Aurantii Immaturus 10 parts, Magnolia officinalis 10 parts, Aucklandia lappa 20 parts, Radix Paeoniae Rubra 10 parts, Prunus persica 10 parts, Salvia miltiorrhiza 10 parts, Lonicera japonica 10 parts, Scutellaria baicalensis 10 parts, Cannabis sativa seed 8 parts, Rheum palmatum 10 parts, Natrii Sulfas 15 parts.

[0012] Further improvement, the Fructus Aurantii Immaturus is stir-fried with bran Fructus Aurantii Immaturus, the Prunus persica is blanched Prunus persica, and the Scutellaria baicalensis is wine-processed Scutellaria baicalensis.

[0013] Further improvement, the traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis further comprises pharmaceutically acceptable pharmaceutical excipients.

[0014] Further improvement, for the traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis, the pharmaceutical excipients are pharmaceutically acceptable carriers, diluents, excipients.

[0015] In the second aspect, a preparation method of a traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis, comprising the following steps:

[0016] Soak Fructus Aurantii Immaturus, Magnolia officinalis, Aucklandia lappa, Radix Paeoniae Rubra, Prunus persica, Salvia miltiorrhiza, Lonicera japonica, Scutellaria baicalensis and Cannabis sativa seed in water, extract 2 to 4 times by decoction method, combine the extracts, concentrate, add Rheum palmatum and continue decocting, and add Natrii Sulfas after the decoction is finished to obtain the traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis.

[0017] Further improvement, the traditional Chinese medicine dosage form of the traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis is traditional Chinese medicine decoction, traditional Chinese medicine granule, traditional Chinese medicine tablet, traditional Chinese medicine capsule, traditional Chinese medicine dropping pill, traditional Chinese medicine syrup or traditional Chinese medicine ointment.

[0018] In the third aspect, the application of the traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis in the preparation of drugs for treating intestinal obstruction.

[0019] Fourthly, the application of the traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis in the preparation of drugs for treating acute pancreatitis, especially having particularly good curative effects on edematous acute pancreatitis.

[0020] The prescription of the present invention has the following functions and indications:

[0021] Laxative and defecation-promoting, promoting qi and activating blood circulation, clearing heat and detoxifying. Applicable to qi stagnation type intestinal obstruction (simple intestinal obstruction), heat accumulation type intestinal obstruction (strangulated intestinal obstruction), stasis obstruction type intestinal obstruction (intestinal adhesion or neoplastic intestinal obstruction).

[0022] The prescription of the present invention is based on the classic famous prescription, the Major Qi-Regulating Decoction in Treatise on Cold Pathogenic Diseases written by Zhang Zhongjing in the Han Dynasty. Seven traditional Chinese medicines, Aucklandia lappa, Cannabis sativa seed, Scutellaria baicalensis, Lonicera japonica, Paeonia lactiflora, Prunus persica, and Salvia miltiorrhiza, are added and the dosages are continuously explored and adjusted. Based on the clinical application effects, an empirical prescription with characteristics for treating adhesive intestinal obstruction is formed.

[0023] Reasons for modification and addition:

[0024] ① Adding Aucklandia lappa synergistically with Immature Bitter Orange and Magnolia officinalis to break qi and reduce accumulation, promote qi movement and relieve pain, so as to treat qi stagnation type intestinal obstruction.

[0025] ② Adding Paeonia lactiflora, Prunus persica, and Salvia miltiorrhiza to dredge blood stasis, promote blood circulation and remove stasis, and jointly achieve the effect of promoting qi movement to promote blood circulation, so as to achieve the purpose of promoting both qi and blood movement and jointly relieve the symptoms of abdominal distension and pain of the patient. Thus, it can treat stasis obstruction type intestinal obstruction.

[0026] ③ Adding Lonicera japonica and Scutellaria baicalensis to clear heat and detoxify to relieve the heat-toxic blood syndrome of the patient.

[0027] ④ Adding Cannabis sativa seed and Prunus persica to moisten the intestines and promote defecation to relieve the drastic purgative power of Rheum officinale and Natrii Sulfas.

[0028] ⑤ Adding Paeonia lactiflora synergistically with Rheum officinale to cool blood and remove stasis; using Lonicera japonica and Scutellaria baicalensis to inhibit the inflammatory reaction; thus treating stasis obstruction type intestinal obstruction.

[0029] All the medicines are used together to jointly achieve the effects of promoting qi movement to relieve pain, purging and reducing accumulation, moistening the intestines and dredging the interior, clearing heat and detoxifying, so as to stop vomiting, cause the stomach qi to descend, make the exhaust and defecation unobstructed, and promote the recovery of gastrointestinal function.

[0030] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0031] 1. The traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis of the present invention can treat qi stagnation type intestinal obstruction (simple intestinal obstruction), heat accumulation type intestinal obstruction (strangulated intestinal obstruction), stasis obstruction type intestinal obstruction (intestinal adhesion or neoplastic intestinal obstruction), expands the treatment scope of the Major Qi-Regulating Decoction, and has remarkable curative effects.

[0032] 2. The traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis of the present invention can also treat edematous acute pancreatitis. Description of the Drawings

[0033] Figure 1 It is a pathological section diagram of the ileocecal part of rats in the blank control group;

[0034] Figure 2 It is a pathological section diagram of the ileocecal part of rats in the sham operation group;

[0035] Figure 3 It is one of the pathological section diagrams of the ileocecal part of rats in the model group;

[0036] Figure 4 It is another pathological section diagram of the ileocecal part of rats in the model group;

[0037] Figure 5 It is a pathological section diagram of the ileocecal part of rats in the low-dose group;

[0038] Figure 6 It is a pathological section diagram of the ileocecal part of rats in the medium-dose group;

[0039] Figure 7 It is a pathological section diagram of the ileocecal part of rats in the high-dose group;

[0040] Figure 8 It is a pathological section diagram of the ileocecal part of rats in the positive control group. Detailed Implementation Modes

[0041] The present invention will be further described in detail below through specific examples in conjunction with the accompanying drawings.

[0042] Example 1

[0043] 1 Materials

[0044] 1.1 Animals

[0045] 72 SPF-grade healthy male SD rats, with a body weight of 180-220 g, were purchased from Jinan Pengyue Experimental Animal Breeding Co., Ltd., license number: SCXK(Lu)20190003. Breeding environment: Animal room of the School of Pharmacy, Anhui University of Chinese Medicine (relative humidity: 50%-70%, temperature: 25±2°C, 12-hour day and night alternation). The rats were housed in separate cages and ventilated regularly. The experiment was approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine, and the animal experiment ethics certificate number: 2024010.

[0046] 1.2 Test Drugs and Formulas

[0047] The prescription described in the present invention is: stir-fried Fructus Aurantii Immaturus 10 g, Magnolia officinalis 10 g, Aucklandia lappa 20 g, Radix Paeoniae Rubra 10 g, semen Persicae 10 g, Salvia miltiorrhiza 10 g, Lonicera japonica 10 g, Scutellaria baicalensis Georgi 10 g, Cannabis sativa L. 8 g, Rheum palmatum L. 10 g (added later), mirabilite 15 g (taken orally after dissolving).

[0048] The Chinese herbal pieces in the formula, such as Magnoliae Officinalis Cortex, Aurantii Fructus Immaturus, Rhei Radix et Rhizoma, Aucklandiae Radix, Cannabis Semen, Scutellariae Radix, Lonicerae Japonicae Flos, Paeoniae Radix Rubra, Persicae Semen, Salviae Miltiorrhizae Radix, Natrii Sulfas (provided by Chuzhou Hospital of Integrated Traditional Chinese and Western Medicine and identified by Associate Professor Xie Dongmei of Anhui University of Chinese Medicine), and the decoction of Dachengqi Decoction (provided by Chuzhou Hospital of Integrated Traditional Chinese and Western Medicine).

[0049] 1.3 Reagents

[0050] Urethane reagent (Sinopharm Chemical Reagent Co., Ltd., batch number: 20160920), 0.9% sodium chloride injection (Jiangxi Kelun Pharmaceutical Co., Ltd., batch number: C23090703), 4% paraformaldehyde (Beijing Lanjeck Technology Co., Ltd., batch number: 71032700), ELISA kits for IL-1β, IL-6, and TNF-α (Enzyme linked immunosorbentassay, ELISA) (Shanghai Jianglai Biotechnology Co., Ltd., batch numbers: JL2022050001, JL2022050001, JL2022050001).

[0051] 1.4 Instruments

[0052] Decoction pot (SW-30Y09, Zhejiang Supor Co., Ltd.), electronic analytical balance (YP-5102, Shanghai Guangzheng Medical Instrument Co., Ltd.), automatic ice maker (IMS-20, Changshu Xueke Electric Appliance Co., Ltd.), centrifuge (LC-4016, Anhui University of Science and Technology Zhongjia), micropipette (Eppendorf, Germany).

[0053] 2 Methods and Results

[0054] 2.1 Preliminary Pharmacodynamic Evaluation

[0055] 2.1.1 Selection of Positive Drugs

[0056] The principle of traditional Chinese medicine in the clinical treatment of intestinal obstruction is that "the six fu-organs function normally when unobstructed", "pain occurs when there is obstruction, and pain subsides when there is no obstruction", and the treatment direction is to promote defecation and purge, activate blood circulation to remove stasis, promote qi movement to relieve stagnation, and clean the intestines and stomach. Dachengqi Decoction has the effects of promoting defecation and activating blood circulation, purging the bowels, etc., can increase gastrointestinal motility, reduce the inflammatory level, and is commonly used in the treatment of postoperative intestinal obstruction. Moreover, the prescription described in the present invention is obtained by repeatedly verifying the effects, adding and subtracting medicinal flavors according to the actual situation of clinical patients on the basis of Dachengqi Decoction. Therefore, Dachengqi Decoction is selected as the positive control drug.

[0057] 2.1.2 Preparation of Test Drugs

[0058] Dachengqi Decoction: Take the single-day prescription amount of Fructus Aurantii Immaturus and Magnoliae Officinalis Cortex, add 10 times the amount of water and soak for 30 minutes, extract by decoction 3 times, each time for 30 minutes. After combining the filtrates, concentrate to about 200 mL, add Rhei Radix et Rhizoma and continue to decoct for 10 minutes, make up the volume to 200 mL, and add Natrii Sulfas, then the positive control drug containing 0.285 g·mL of crude drug is obtained. -1 of the positive control drug.

[0059] The prescription described in the present invention: Weigh the single-day prescription amount of cut crude drugs (except Rhei Radix et Rhizoma and Natrii Sulfas), which is consistent with the preparation process of Dachengqi Decoction. After making up the volume to 200 mL, add Natrii Sulfas as the test drug. The test drug is respectively made up the volume to contain 0.3075 g, 0.615 g, and 1.230 g of crude drug per milliliter, and then the low-, medium-, and high-dose test drugs are obtained.

[0060] 2.1.3 Modeling method

[0061] The semi-ligation method is used for modeling. The rats are fasted for 12 hours, and anesthetized thoroughly with 5 mL·kg of 20% urethane -1 and the skin is prepared and disinfected. After opening the abdomen along the midline of the abdomen, take out the gastrointestinal tract of the rats. Gently wipe and squeeze the whole intestine from the pylorus to the ileocecal part with a moist sterile cotton swab, and use a toothed forceps to squeeze at about 3 cm intervals until punctate bruises appear. Then place a central venous catheter closely against the intestine 3 cm away from the ileocecal part, tie it with a surgical thread and carefully draw out the central venous catheter, and then smooth the intestine and put it back into the abdominal cavity and suture and disinfect layer by layer. In the sham operation group, only the abdomen is opened and the mesentery is penetrated with a needle and thread but not ligated, and the control group does not undergo any surgical treatment. Change the bedding in time after the operation to prevent the rats from being infected.

[0062] One day after the operation, randomly select 4 rats from the model group and the sham operation group respectively, and divide them into two groups on average. One group is used to compare the fecal volume and water content. The other group is intragastrically administered with a carbon powder suspension in normal saline according to the dose, and the intestinal propulsion rate of the rats is calculated and compared to judge whether the modeling is successful.

[0063] 2.1.4 Grouping and administration

[0064] There are 8 rats in the blank control group, 12 rats in the sham operation group, among which 4 rats are used to evaluate the modeling, and 52 rats are used to establish the rat intestinal obstruction model. 6 rats are lost during the modeling process. Because the rats in this model are prone to loss, 4 rats with intestinal obstruction are used to evaluate the modeling. The successfully modeled rats are divided into 10 rats in the model group, 8 rats in each of the low-, medium-, and high-dose groups of the prescription described in the present invention and the positive control group of Dachengqi Decoction.

[0065] Taking the classic famous prescription Dachengqi Decoction as the positive control drug, the rats in the positive control group, low-, medium-, and high-dose groups are respectively intragastrically administered with the corresponding test drug 1 mL·100 g -1 , and the corresponding test drug of equal dose is given by enema 1 hour after administration, 2 times / d, for a total of 10 times. The rats in the remaining groups are administered with an equal volume of normal saline.

[0066] 2.1.5 Detection indicators

[0067] 2.1.5.1 Observation of pathological changes in the ileocecal region

[0068] Take the ileum tissue near the ileocecal region, fix it in 4% paraformaldehyde solution, dehydrate it with ethanol, embed it in paraffin, section it, and after staining with hematoxylin and eosin (HE), observe the pathological changes of the intestinal tissue under an optical microscope.

[0069] The pathological section results of the ileum tissue of rats in each group are as Figures 1-8 shown. The ileum mucosal structure of the blank control group is normal, the crypt boundaries are clear, and they are arranged neatly ( Figure 1 ). There is no significant difference between the sham operation group and the blank control group ( Figure 2 ). Compared with the blank control group and the sham operation group, the serosa layer of the model group showed obvious edema and congestion, a large number of red blood cells could be seen, the crypts were distorted and branched, and a large number of inflammatory cells infiltrated ( Figure 3 , 4 ). In the low-dose group, the serosa layer peeled off, showed obvious edema, the crypt structure was absent, a large number of red blood cells could be seen, and the degree of inflammatory cell infiltration was lower ( Figure 5 ). In the medium-dose group, the ileum structure was complete, occasional tissue edema, exfoliation and sporadic inflammatory cell infiltration were seen, and the degree was lower than that of the model group and the low-dose group ( Figure 6 ). The high-dose group showed a complete structure, rare tissue exfoliation, a small degree of edema, clear and neat crypt boundaries, almost no congestion caused by in vivo inflammation, and a relatively small number of red blood cells ( Figure 7 ). Finally, the positive control group was similar to the high-dose group, with a complete structure and a small number of red blood cells ( Figure 8 ).

[0070] 2.1.5.2 Detection of the levels of IL-1β, IL-6 and TNF-α in rat serum

[0071] Fast the rats for 12 h before surgery and allow free access to water. 1 h after the last administration, anesthetize the rats with 5 mL·kg -1 of 20% urethane, collect 5 - 10 mL of blood from the abdominal aorta, let it stand at room temperature for 2 h, transfer it to a 4°C refrigerator and let it stand for another 4 h, then centrifuge it at 3000 rpm for 15 min, collect the serum, and store it in a -20°C refrigerator for later use. Take it out before detection, let it stand at room temperature for 1 h, and then operate according to the instructions of the ELISA kit to detect the contents of IL-1β, IL-6 and TNF-α in rat serum respectively.

[0072] The levels of IL-1β, IL-6 and TNF-α in the sera of rats in each group are shown in Table 5. Compared with the blank control group, there were no significant differences in the levels of IL-1β, IL-6 and TNF-α in the sham operation group (P > 0.05); the levels of IL-1β, IL-6 and TNF-α in the model group were significantly higher than those in the sham operation group (P < 0.01); compared with the model group, the levels of IL-1β in the low-dose group and the medium-dose group were significantly lower than those in the model group (P < 0.05), and the levels of IL-6 and TNF-α were significantly lower than those in the model group (P < 0.01); the levels of IL-1β, IL-6 and TNF-α in the high-dose group and the positive control group were significantly lower than those in the model group (P < 0.01).

[0073] Table 1 Levels of IL-1β, IL-6 and TNF-α in the sera of rats in each group

[0074] Group <![CDATA[IL-1β / (ng·L -1 )]]> <![CDATA[IL-6 / (pg·mL -1 )]]> <![CDATA[TNF-α / (ng·L -1 )]]> Low-dose group / (n = 6) <![CDATA[44.24±1.90 ** > <![CDATA[147.59±7.45 ** > <![CDATA[412.77±22.43 ** > Medium-dose group / (n = 6) <![CDATA[47.21±2.89 * > <![CDATA[147.18±5.65 ** > <![CDATA[474.57±30.58 ** > High-dose group / (n = 6) <![CDATA[45.23±2.03 ** > <![CDATA[134.67±4.20 ** > <![CDATA[455.83±24.64 ** > Model group / (n = 8) <![CDATA[51.03±4.55 ## > <![CDATA[159.17±7.09 ## > <![CDATA[578.79±48.75 ## > Sham operation group / (n = 7) 41.77±3.53 122.06±4.14 418.79±43.08 Blank control group / (n = 6) 39.12±2.05 119.74±4.25 404.00±51.78 Positive control group / (n = 6) <![CDATA[45.16±2.38 ** > <![CDATA[136.47±4.35 ** > <![CDATA[437.52±28.46 ** > F 0.19 0.10 0.68

[0075] ## indicates P < 0.01 compared with the sham operation group, * indicates P < 0.05 compared with the model group, and ** indicates P < 0.01 compared with the model group.

[0076] 2.2 Statistical analysis method

[0077] This experiment was statistically analyzed based on SPSS 26.0 software, and GraphPad Prism 9.0.0 software was used for drawing. The statistical results were expressed as mean ± standard deviation If the data conform to the normal distribution, one-way analysis of variance is performed on the inter-group results, and the LSD method is used for testing when the variances are homogeneous. If the data do not conform to the normal distribution, non-parametric tests are used. P < 0.05 indicates that the difference is statistically significant.

[0078] 2.3 Conclusion

[0079] Adhesive intestinal obstruction, except for congenital intestinal dysplasia, is mostly caused by intra-abdominal surgery, bleeding, inflammation, foreign bodies, etc. Inflammation, ischemia or serosal injury will stimulate deep mast cells and mesothelial cells, resulting in an increase in fibrin. If it cannot be absorbed in time, it will cause obstruction.

[0080] Through a large number of experiments, among the screened potential pathways, the PI3K / Akt signaling pathway consists of PI3K with lipid kinase activity phosphorylating phosphatidylinositol 3-hydroxy and downstream Akt. PI3K plays a key role in pathways such as apoptosis, pyroptosis, and oxidative stress of cells. After activation, it activates Akt through phosphorylated Akt phosphorylation sites, regulating multiple downstream proteins to participate in regulating cell survival, proliferation, apoptosis, etc., thereby reducing the expression of body inflammatory factors and mediating the inflammatory response. It is suggested that the prescription described in the present invention can improve intestinal obstruction by improving the inflammatory response. Therefore, experiments were selected to detect the levels of serum inflammatory factors for a preliminary pharmacodynamic evaluation of the prescription described in the present invention.

[0081] IL-6 is a typical cytokine maintaining homeostasis in the body. When the internal environment in the body is out of balance, IL-6 will be immediately produced, but excessive production will have a pathological impact on the acute systemic inflammatory response syndrome. IL-1β is an effective pro-inflammatory cytokine produced by cells of the innate immune system and can be induced to generate when the body is stimulated by the outside world. TNF-α is mainly produced by activated macrophages and T lymphocytes. An increase in TNF-α levels is found in inflammatory and infectious diseases, and the level is related to the severity of the infection. TNF can also induce programmed necrosis in an inflammatory environment. The experimental results show that when AIO-related symptoms appear, the levels of IL-6, IL-1β, and TNF-α in the experimental rats are higher than those in normal rats. After administration, the related inflammatory response is inhibited, the inflammatory environment in the rats is improved, and the levels of these three serum inflammatory factors are reduced.

[0082] In summary, the prescription described in the present invention has certain pharmacodynamic effects on the treatment of intestinal obstruction, can act on multiple targets and multiple pathways, and can mediate the inflammatory response by affecting the mRNA expression of inflammatory factors or by reducing the expression of inflammatory factors through affecting multiple pathways, thereby treating intestinal obstruction.

[0083] Example 2

[0084] Clinical symptoms of acute pancreatitis (edematous type):

[0085] 1. Acute abdominal pain

[0086] The main symptom of acute edematous pancreatitis is acute abdominal pain, mostly manifested as continuous upper abdominal pain. Patients often get sick after eating or drinking. Usually, patients will have pain of varying degrees. Patients with mild symptoms show mild dull pain, and patients with severe symptoms show colic.

[0087] 2. Abdominal distension: Due to intestinal paralysis (inflammation affecting the mesentery or celiac plexus), intestinal peristalsis is weakened. Decreased bowel sounds: Reflecting intestinal paralysis.

[0088] 3. Vomiting

[0089] Most patients will also experience vomiting symptoms. Usually, after eating, patients will vomit out the food that has just entered the stomach. Patients with severe conditions will vomit bile.

[0090] 3. Fever

[0091] Some patients have a fever due to inflammation in the body. Usually, the body temperature of a feverish patient is within 39. If it exceeds 39 and the fever persists, it can be considered a combined infection.

[0092] According to traditional Chinese medicine theory, for acute pancreatitis (edematous type), the treatment principle is to clear heat and detoxify, promote defecation to relieve constipation, promote qi circulation and activate blood circulation. The prescription described in the present invention can be used to treat acute pancreatitis (edematous type). The treatment theory is as follows:

[0093] Compare the components of the traditional Chinese medicine in the prescription of the present invention pairwise, screen out all common components, and then import the Chinese medicine names, single-herb components, common components, and intersection gene targets into Cytoscape 3.9.1. Use the CytoNCA plug-in to analyze the data, obtain multiple parameters such as Degree, Betweenness Centrality, and Closeness Centrality, and construct a "traditional Chinese medicine-component-target" network according to the Degree value results. Conduct GO and KEGG pathway enrichment analysis to obtain the core targets, arrange them in descending order according to the P value, and conduct KEGG pathway analysis (P < 0.01) to screen the signal pathways related to pancreatitis. The results are shown in Table 2:

[0094] Table 2 KEGG signal pathways of component-disease targets (related to pancreatitis)

[0095]

[0096]

[0097] The MAPK signaling pathway also plays an important role in acute pancreatitis. The activation of the MAPK pathway can lead to the release of pro-inflammatory factors, exacerbating the pancreatic inflammatory response. Studies on acupuncture treatment of acute pancreatitis have shown that by regulating the MAPK signaling pathway, the inflammatory response can be effectively reduced.

[0098] The PI3K / Akt signaling pathway plays a role in acute pancreatitis mainly by regulating the inflammatory response and apoptosis. The activation of Akt can inhibit the release of inflammatory factors and reduce apoptosis, but over-activation may lead to pancreatic regeneration disorders. Therefore, moderately regulating the PI3K / Akt signaling pathway may be helpful for the treatment of acute pancreatitis.

[0099] It was found through GO-KEGG pathway enrichment analysis that it mainly involves the PI3K-Akt signaling pathway, MAPK signaling pathway, etc.; the molecular docking results show that the binding ability of the component targets is good, having a certain pharmacodynamic basis.

[0100] Therefore, the prescription described in the present invention is multi-target and multi-pathway in the treatment of acute pancreatitis, and can play a role in treating acute pancreatitis by inhibiting the expression of proteins related to signal pathways such as PI3K / AKT and down-regulating the levels of various inflammatory factors.

[0101] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention can have various changes and modifications. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis, characterized in that, Comprising the following parts by mass of traditional Chinese medicine raw materials: Fructus Aurantii Immaturus 10±1 part, Magnolia officinalis 10±1 part, Aucklandia lappa 20±1 part, Radix Paeoniae Rubra 10±1 part, Prunus persica 10±1 part, Salvia miltiorrhiza 10±1 part, Lonicera japonica 10±1 part, Scutellaria baicalensis 10±1 part, Cannabis sativa seed 8±1 part, Rheum palmatum 10±1 part, Mirabilitum 15±1 part.

2. The traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis according to claim 1, wherein, Comprising the following parts by mass of traditional Chinese medicine raw materials: Fructus Aurantii Immaturus 10 parts, Magnolia officinalis 10 parts, Aucklandia lappa 20 parts, Radix Paeoniae Rubra 10 parts, Prunus persica 10 parts, Salvia miltiorrhiza 10 parts, Lonicera japonica 10 parts, Scutellaria baicalensis 10 parts, Cannabis sativa seed 8 parts, Rheum palmatum 10 parts, Mirabilitum 15 parts.

3. The traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis according to claim 1, wherein: The Fructus Aurantii Immaturus is selected as stir-fried Fructus Aurantii Immaturus with bran, the Prunus persica is selected as blanched Prunus persica, and the Scutellaria baicalensis is selected as wine-processed Scutellaria baicalensis.

4. The traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis according to claim 1, wherein: It further comprises pharmaceutically acceptable pharmaceutical excipients.

5. The traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis according to claim 4, wherein: The pharmaceutical excipients are pharmaceutically acceptable carriers, diluents, and excipients.

6. The preparation method of a traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis according to any one of claims 1 to 5, characterized in that, Comprising the following steps: Soak Fructus Aurantii Immaturus, Magnolia officinalis, Aucklandia lappa, Radix Paeoniae Rubra, Prunus persica, Salvia miltiorrhiza, Lonicera japonica, Scutellaria baicalensis, and Cannabis sativa seed in water, extract 2 - 4 times by decoction method, combine the extracts, concentrate, add Rheum palmatum and continue decocting, and add Mirabilitum after the decoction is completed to obtain the traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis.

7. The preparation method of a traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis according to claim 6, wherein: The traditional Chinese medicine dosage form of the traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis is traditional Chinese medicine decoction, traditional Chinese medicine granule, traditional Chinese medicine tablet, traditional Chinese medicine capsule, traditional Chinese medicine dropping pill, traditional Chinese medicine syrup, or traditional Chinese medicine ointment.

8. Use of a traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis according to any one of claims 1 - 5 in the preparation of a medicament for treating intestinal obstruction.

9. Use of a traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis according to claim 8 in the preparation of a medicament for treating intestinal obstruction, characterized in that: The treatment can be used for treating drugs for qi-stagnation type intestinal obstruction (simple intestinal obstruction), heat-binding type intestinal obstruction (strangulated intestinal obstruction), and stasis-obstruction type intestinal obstruction (intestinal adhesion or neoplastic intestinal obstruction).

10. Use of a traditional Chinese medicine composition for treating intestinal obstruction and acute pancreatitis according to any one of claims 1 - 5 in the preparation of a medicament for treating acute pancreatitis.

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