Application of iron broom extract in the preparation of drugs for the prevention and treatment of postoperative ileus

Abstract

This invention discloses the application of *Hemiberlesia lataniae*, *Hemiberlesia lataniae* extract, or compositions containing *Hemiberlesia lataniae* extract in the preparation of drugs for the prevention and treatment of postoperative ileus, relating to the field of traditional Chinese medicine technology. This invention discovers the use of *Hemiberlesia lataniae*, *Hemiberlesia lataniae* extract, or compositions containing *Hemiberlesia lataniae* extract in the treatment of postoperative ileus, providing a new direction for the treatment of postoperative ileus.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to the application of iron broom, iron broom extract, or compositions containing iron broom extract in the preparation of drugs for the prevention and treatment of postoperative paralytic ileus. Background Technology

[0002] *Lespedeza cuneata*, an annual herb belonging to the genus *Lespedeza* of the legume family, has a sweet and slightly bitter taste and is neutral in nature. It is used to clear heat and dampness, aid digestion, eliminate stagnation, and relieve phlegm and cough. The ethanol extract of *Lespedeza cuneata* exhibits selective excitatory effects on various pregnant animals and isolated uteruses sensitized with diethylstilbestrol, but has no significant effect on isolated uteruses of various non-pregnant animals. *Lespedeza cuneata* contains various flavonoids, as well as phenolic and acidic substances. Zhang Fang et al. studied the relationship between the chemical composition and activity of *Lespedeza cuneata*. 10 kg of dried *Lespedeza cuneata* was pulverized and extracted three times with 95% ethanol under reflux for 2 hours each time. The ethanol was recovered under reduced pressure to obtain an extract. After adding an appropriate amount of water for suspension, the extract was further extracted with petroleum ether, chloroform, ethyl acetate, and water-saturated n-butanol. The petroleum ether fraction was separated by repeated silica gel column chromatography with a petroleum ether-ethyl acetate gradient elution, monitored by thin-layer chromatography, and the same components were combined. The ethyl acetate fraction was separated by repeated silica gel column chromatography with a chloroform-methanol gradient elution, monitored by thin-layer chromatography, and the same components were combined and separated. Eight compounds were isolated and identified from the petroleum ether and ethyl acetate fractions of the ethanol extract: β-sitosterol, n-octacosanol, salicylic acid, vanillic acid, kaempferol, quercetin, kaempferol-3-OBD-glucoside, and daucosterol.

[0003] Postoperative ileus (POI), also known as postoperative gastrointestinal dysfunction (POGD), is a clinical phenomenon following surgery where gastrointestinal motility is temporarily inhibited due to non-mechanical reasons, preventing oral intake. It is defined as a prolonged recovery time of gastrointestinal function after surgery due to non-mechanical factors, making oral intake impossible. Its characteristics include impaired gastrointestinal motility, clinically manifesting as postoperative nausea, vomiting, abdominal pain, and cessation of flatus and defecation. Its pathogenesis involves multiple factors, including surgical trauma, anesthetic drugs, sympathetic nervous system hyperactivity, and intestinal inflammatory response.

[0004] Currently, Traditional Chinese Medicine (TCM) generally combines clinical experience with syndrome differentiation and treatment. Cheng Xiaobin et al. believe that post-intestinal obstruction (POI) is caused by stagnation of Qi and blood in the intestines, leading to poor bowel function. Their treatment principle is to regulate Qi and promote bowel movement, thus regulating the intestines. Therefore, they used rhubarb granules (without decoction), which significantly improved the recovery time of flatus and bowel sounds. Dong Wenting believes that "Qi stagnation" is the main pathogenesis of this disease. Her treatment uses Magnolia officinalis decoction to promote Qi circulation, relieve bloating, and dry dampness, resulting in a significantly better recovery time of gastrointestinal function compared to the control group. Zeng Haiping et al. treat POI with Champagne Formula based on the principles of strengthening the spleen and stomach, promoting Qi circulation, and clearing the bowels, finding that it effectively improves gastrointestinal symptoms.

[0005] Currently, postoperative ileus is influenced by multiple factors and has a complex pathogenesis. Conventional drugs that increase gastrointestinal motility are often ineffective in treating it, and the clinical use of drugs that simply promote gastrointestinal motility may increase the risk of intestinal obstruction. Therefore, there is currently a lack of clearly effective and targeted traditional Chinese medicine ingredients that promote postoperative gastrointestinal recovery. Furthermore, there is no research on the application of *Hemiberlesia lataniae* extract in the treatment of postoperative ileus. Summary of the Invention

[0006] In view of this, the object of the present invention is to provide the use of iron broom, iron broom extract or a composition containing iron broom extract in the preparation of a medicament for postoperative ileus paralysis.

[0007] To achieve the above-mentioned objectives, the technical solution of this invention is as follows:

[0008] On one hand, the present invention provides the use of iron broom, iron broom extract or a composition containing iron broom extract in the preparation of a medicament for the prevention and / or treatment of postoperative paralytic ileus.

[0009] Preferably, the postoperative intestinal paralysis is intestinal paralysis caused by surgical procedures.

[0010] Preferably, the symptoms of postoperative ileus include at least one of impaired gastrointestinal motility, nausea, vomiting, abdominal pain, cessation of flatus, and cessation of defecation.

[0011] Preferably, in the application, the preparation method of the iron broom extract includes the following steps:

[0012] (1) Extract the iron broom herb 2-4 times and combine the extracts to obtain the extract;

[0013] (2) Concentrate the extract obtained in step (1) to obtain a concentrated solution;

[0014] (3) The concentrate obtained in step (2) is subjected to alcohol precipitation and dried to obtain the iron broom extract.

[0015] More preferably, in step (1), the extraction is water extraction or alcohol extraction;

[0016] More preferably, the water extraction is performed as follows: the first extraction is performed by adding 5-10 times the mass of water, with an extraction time of 1-3 hours and a temperature of 95-100℃; the second extraction is performed by adding 4-8 times the mass of water, with an extraction time of 1-2 hours and a temperature of 95-100℃.

[0017] A further preferred method is: first, decoct and extract with 8 times the weight of the medicinal materials in water for 2 hours; second, decoct and extract with 6 times the weight of the medicinal materials in water for 1.5 hours.

[0018] More preferably, in step (2), the concentration method is dual-effect concentration.

[0019] More preferably, the conditions for the dual-effect concentration are:

[0020] Steam pressure: 0.05~0.15MPa; First-effect vacuum: -0.06~-0.09MPa; First-effect concentration temperature: 60~85℃; Concentration time: 100-150min; Relative density of concentrate: 1.0-1.1; Second-effect vacuum:

[0021] -0.06~-0.09MPa, double-effect concentration temperature: 60~85℃; concentration time: 40-80min, relative density of concentrate: 1.1-1.4.

[0022] More preferably, the conditions for the dual-effect concentration are:

[0023] Steam pressure: 0.1 MPa; First-effect vacuum: -0.08 MPa; First-effect concentration temperature: 75℃; Concentration time: 120 min; Relative density of concentrate: 1.05; Second-effect vacuum: -0.08 MPa; Second-effect concentration temperature: 70℃; Concentration time: 60 min; Relative density of concentrate: 1.20.

[0024] More preferably, in step (3), the alcohol precipitation specifically involves adding ethanol to the concentrate to achieve an ethanol content of 50-70%, mixing evenly, and allowing it to stand.

[0025] More preferably, the alcohol precipitation specifically involves adding ethanol to the concentrate to achieve an ethanol content of 60%, mixing thoroughly, and allowing it to stand.

[0026] More preferably, the alcohol precipitation specifically involves: adding ethanol to the concentrate to achieve an ethanol content of 60%, stirring for 30 minutes until the mixture is homogeneous, and then allowing it to stand for 24 hours.

[0027] On the other hand, the present invention provides the use of Kexiemin pills or Kexiemin granules in the preparation of drugs for the prevention and / or treatment of postoperative paralytic ileus.

[0028] Preferably, the active ingredient in the Kexiemin pills or Kexiemin granules is the aforementioned iron broom extract.

[0029] Preferably, the postoperative intestinal paralysis is intestinal paralysis caused by surgical procedures.

[0030] Preferably, the symptoms of postoperative ileus include at least one of impaired gastrointestinal motility, nausea, vomiting, abdominal pain, cessation of flatus, and cessation of defecation.

[0031] More preferably, the Kexiemin pills or Kexiemin granules include the aforementioned iron broom extract, as well as at least one of microcrystalline cellulose, dextrin, starch paste, and sucrose.

[0032] Preferably, the concentration of the starch slurry is 10-20%, more preferably 10%.

[0033] Preferably, in the Kexiemin pill, the mass ratio of the broom extract, microcrystalline cellulose, dextrin and starch paste is 10-20:3-5:10-20:7.5-18.

[0034] As a specific example of the present invention, the Kexiemin pill is composed of iron broom extract, microcrystalline cellulose, dextrin and starch paste.

[0035] As a specific example of the present invention, the preparation method of the Kexiemin pill is as follows: weigh the prescribed amount of iron broom extract, add dextrin and microcrystalline cellulose, mix evenly, add starch paste, make pills, and dry.

[0036] As a specific example of the present invention, the preparation method of the Kexiemin granules is as follows: add sucrose, mix well, granulate, and dry.

[0037] The beneficial effects of this invention are as follows:

[0038] This invention discovers the use of prepared iron broom, iron broom extract, or compositions containing iron broom extract in the treatment of postoperative ileus, solving the problem that the treatment of ileus caused by surgery is more difficult, and that conventional prokinetic drugs are not ideal for the treatment of postoperative ileus, thus providing a new direction for the treatment of postoperative ileus. Attached Figure Description

[0039] Figure 1 This is a diagram of the small intestine propulsion experiment for the normal control group.

[0040] Figure 2 This is a diagram of the small intestine propulsion experiment in the model group.

[0041] Figure 3 This is a diagram of the small intestine propulsion experiment in Example 1.

[0042] Figure 4 Morphological observation of jejunal tissue sections from each group of rats (×100).

[0043] Figure 5 Morphological observation of ileal tissue sections from each group of rats (×100). Detailed Implementation

[0044] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the invention based on the disclosed content, which should also fall within the scope of protection claimed in this application.

[0045] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all chemical reagents used in the embodiments of the present invention were obtained through conventional commercial means. Unless otherwise specified, all contents mentioned below are mass contents. Unless otherwise specified, it is understood that the process was carried out at room temperature.

[0046] Metoclopramide tablets (Reglan tablets) were purchased from Tianjin Lisheng Pharmaceutical Co., Ltd., approval number: National Drug Approval Number H12020161; Magnolia officinalis gas-relieving compound was purchased from Ruiyang Pharmaceutical Co., Ltd., approval number: National Drug Approval Number Z20050563; Sodium pentobarbital and dextran blue-2000 were purchased from Maclean Company; Povidone-iodine (batch number: 20230702) was purchased from Shandong Anjie High-Tech Disinfection Technology Co., Ltd.; EnSpire multi-functional microplate reader (Perkin Elmer, USA); D3024R high-speed refrigerated centrifuge (Dalong Medical Equipment Co., Ltd.).

[0047] Example 1

[0048] (1) Extract the iron broom herb with water twice. The first extraction is carried out with 8 times the weight of the herb and boiled for 2 hours at 50°C. The second extraction is carried out with 6 times the weight of the herb and boiled for 1.5 hours. The extracts are combined to obtain the extract.

[0049] (2) The extract obtained in step (1) is concentrated using a double-effect concentration method. The conditions for double-effect concentration are as follows: steam pressure: 0.1 MPa; first-effect vacuum: -0.08 MPa; first-effect concentration temperature: 75℃; concentration time: 120 min; relative density of concentrate: 1.05; second-effect vacuum: -0.08 MPa; second-effect concentration temperature: 70℃; concentration time: 60 min; relative density of concentrate: 1.20. The concentrate is then obtained.

[0050] (3) Add ethanol to the concentrate obtained in step (2) to make the ethanol content reach 60%, stir for 30 minutes until it is evenly mixed, let stand for 24 hours, filter, vacuum concentrate and dry for 3 days, collect the paste directly, weigh the dried paste after crushing, seal and bag it to obtain the iron broom extract.

[0051] Example 2

[0052] (1) Extract the iron broom herb with water twice. The first extraction is carried out with 5 times the weight of the herb and boiled for 3 hours at 60℃. The second extraction is carried out with 8 times the weight of the herb and boiled for 1 hour at 40℃. The extracts are combined to obtain the extract.

[0053] (2) The extract obtained in step (1) is concentrated using a double-effect method. The conditions for double-effect concentration are as follows: steam pressure: 0.15 MPa; first-effect vacuum: -0.09 MPa; first-effect concentration temperature: 85℃; concentration time: 150 min; relative density of concentrate: 1.10; second-effect vacuum: -0.06 MPa; second-effect concentration temperature: 60℃; concentration time: 40 min; relative density of concentrate: 1.30. The concentrate is then obtained.

[0054] (3) Add ethanol to the concentrate obtained in step (2) to make the ethanol content reach 70%, stir for 30 minutes until it is evenly mixed, let stand for 24 hours, filter, vacuum concentrate and dry for 3 days, collect the paste directly, weigh the dried paste after crushing, seal and bag it to obtain the iron broom extract.

[0055] Example 3

[0056] (1) Extract the iron broom herb with water 4 times. For the first and second extractions, add 10 times the weight of the herb with water and decoct for 1 hour at 40°C. For the third and fourth extractions, add 4 times the weight of the herb with water and decoct for 2 hours at 60°C. Combine the extracts to obtain the final extract.

[0057] (2) The extract obtained in step (1) is concentrated using a double-effect method. The conditions for double-effect concentration are as follows: steam pressure: 0.05 MPa; first-effect vacuum: -0.06 MPa; first-effect concentration temperature: 60℃; concentration time: 100 min; relative density of concentrate: 1.0; second-effect vacuum: -0.09 MPa; second-effect concentration temperature: 85℃; concentration time: 80 min; relative density of concentrate: 1.40. The concentrate is then obtained.

[0058] (3) Add ethanol to the concentrate obtained in step (2) to make the ethanol content reach 50%, stir for 30 minutes until it is evenly mixed, let stand for 24 hours, filter, vacuum concentrate and dry for 3 days, collect the paste directly, weigh the dried paste after crushing, seal and bag it to obtain the iron broom extract.

[0059] Preparation Example 1

[0060] Unlike Example 1, in step (1), 50% ethanol was used for extraction in Example 1, and the extraction was performed twice. Each time, 5 times the mass of the medicinal material was added to the 50% ethanol, and the extraction was carried out at 40°C for 2 hours. The extracts were then combined. The remaining steps were the same.

[0061] Preparation Example 2

[0062] Unlike Example 1, step (1) is as follows: extract the iron broom herb with 50% ethanol 4 times, each time adding 10 times the mass of the herb with 70% ethanol, soaking and extracting at 50°C for 4 hours, and combining the extracts to obtain the extract.

[0063] Preparation Example 3

[0064] Unlike Example 1, step (1) is as follows: extract the iron broom herb with 70% ethanol twice, adding 5 times the mass of the herb with 70% ethanol each time, soaking and extracting at 40°C for 2 hours, and combining the extracts to obtain the extract.

[0065] Preparation Example 4

[0066] Unlike Example 1, step (1) is as follows: extract the iron broom herb with 70% ethanol 4 times, each time adding 10 times the mass of the herb with 70% ethanol, soaking and extracting at 50°C for 4 hours, and combining the extracts to obtain the extract.

[0067] Preparation Example 5

[0068] Unlike Example 1, in step (2), Preparation Example 2 uses evaporation and concentration to concentrate to a relative density of 1.20 to obtain a concentrated solution. The remaining steps are the same.

[0069] Preparation Example 6

[0070] Unlike Example 1, in step (2), Preparation Example 2 uses evaporation and concentration to concentrate to a relative density of 1.40, obtaining a concentrated solution. The remaining steps are the same.

[0071] Results Test

[0072] A rat model of postoperative ileus induced by friction was used to simulate surgery. The efficacy of the extract in treating postoperative ileus induced by this method was evaluated using gastrointestinal motility tests, histopathological examination, and inflammatory factor analysis. Simultaneously, a New Zealand rabbit model of gastrointestinal ileus induced by colectomy was used to evaluate the efficacy of the extract in treating postoperative ileus induced by this method, using indicators such as postoperative bowel sound recovery time and first defecation time. All experimental results are presented as... The experimental data were analyzed using Graph-pad Prism 8.0 software. Statistical differences between each group and the control group were compared using one-way ANOVA and Dunnett's t-test.

[0073] Test Example 1: Experiment on the Animal Model of Postoperative Intestinal Paralysis in Rats

[0074] 1. Method

[0075] 1.1 Animals and Grouping

[0076] SPF-grade male SD rats, weighing 160 - 200 g, were purchased from Shanghai Slack Experimental Animal Co., Ltd. (License No.: SCXK(Shanghai)2022 - 0004; Certificate No.: 20220004032973). They were conventionally raised in the Experimental Animal Center of Nanjing University of Chinese Medicine. After 7 days of adaptive feeding, they were randomly divided into groups of 12 each: a normal control group (control), a model group (model), a sham operation group (J), a Houpu Paqi Mixture group (P), a metoclopramide group (W), and three example groups.

[0077] 1.2 Model Establishment and Administration Method

[0078] Rats in each group were fasted 12 h before surgery. Except for the animals in the normal control group, rats in the other groups were anesthetized by intraperitoneal injection of 1% sodium pentobarbital according to their body weight, their fur was prepared, and the abdominal incision site was routinely disinfected and covered with a sterile gauze. A vertical incision of about 2 cm was made in the midline of the abdomen. After the small intestine of the rats in the model group and each administration group was placed on a gauze containing normal saline, a slightly wet cotton swab of normal saline was used to rub the small intestine back and forth 3 times from the proximal jejunum to the terminal ileum and then from the terminal ileum to the proximal jejunum within 5 min. It was appropriate for the small intestine to be moderately congested and edematous. After the intestinal manipulation of the rats was completed, the small intestine was gently placed back into the intestinal cavity, and the abdominal muscle layer and skin wound were sutured separately with 5 - 0 silk thread. After suturing, the wound was disinfected again to prevent infection. Successful modeling was achieved when there was a certain degree of intestinal adhesion in the small intestine, increased exudation around it, and obvious inhibition of gastrointestinal motility. Rats in the sham operation group had a 2 - cm abdominal incision and were left stationary for 6 min, during which the small intestine was not taken out for wiping.

[0079] Each administration group was given intragastric administration at the specified dose 3 h after surgery, and the normal control group, sham operation group, and model group were given an equal volume of normal saline.

[0080] Table 1.

[0081] test substance Dosage physiological saline — physiological saline — physiological saline — Magnolia officinalis decomposition compound 8.94 mL / kg TSZ Iron Broom Extract 1.3g / kg Metoclopramide group 8mg / kg

[0082] [[ID=2十七]]2. Experimental Method

[0083] Each group of rats was given intragastric administration of dextran blue - 2000 (20 g / L), 1.5 mL / rat, 30 min before being sacrificed. Rats were sacrificed 24 h after surgery, and the gastric emptying rate, gastric volume, and small intestine propulsion (small intestine propulsion rate, relative percentage of dextran blue - 2000 in each segment of the small intestine) of the rats were measured respectively.

[0084] 2.1 Measurement of Gastric Volume

[0085] Tie the anterior and posterior ends of the stomach together with a string, place it in a 50mL centrifuge tube containing a fixed volume of water, observe the rise of the water level, and record the volume change, which is the stomach volume.

[0086] 2.2 Gastric emptying rate determination

[0087] The stomach was minced, and distilled water was added to a final volume of 20 mL. The mixture was thoroughly mixed and centrifuged at 13000 rpm for 5 min. The supernatant was collected, and the absorbance (Ag) of the residual pigment in the stomach and the pigment in the standard tube was measured using an EnSpire multi-functional microplate reader at a wavelength of 620 nm. 胃内残留 ) value. Gastric emptying percentage (%) = (1-A 胃内残留 / A 标准管 )×100%, A 标准管 Add water to 1.5 mL of dextran blue-2000 (20 g / L) to a final volume of 20 mL, and measure the A value at 620 nm.

[0088] 2.3 Determination of small intestinal propulsion rate

[0089] Lay the small intestine flat on a cardboard and straighten it naturally. Measure the distance from the pyloric sphincter to the ileocecal junction (M) and the distance from the pyloric sphincter to the front of the pigment (m). The small intestine propulsion rate (%) = m / M × 100%.

[0090] Small intestinal propulsion movements of the normal control group, model group, and Example 1 group are as follows: Figures 1-3 As shown.

[0091] 2.4 Assessment of the intestinal segment with the highest relative percentage of small intestinal dextran blue-2000

[0092] Divide the small intestine into 10 equal parts and place them into labeled centrifuge tubes. After chopping, add distilled water to a volume of 2 mL, mix well, and centrifuge at 13000 rpm for 5 min. Collect the supernatant and measure the absorbance (A) at 620 nm using an EnSpire microplate reader. i Values ​​of i = 1, 2, ..., 10, and the relative percentage (%) of dextran blue-2000 in each segment of the small intestine = A i / (A1+A2+……+A 10 The percentage of small intestinal dextran blue-2000 was calculated as 100%, and the intestinal segment with the highest relative percentage of small intestinal dextran blue-2000 was determined. The higher the value of the intestinal segment, the better the small intestinal motility.

[0093] 2.5 Pathological and Histological Observation

[0094] Rat small intestinal tissue was collected in transverse sections, including the jejunum and ileum. After removing intestinal contents, the tissue was fixed with 4% paraformaldehyde tissue fixative, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (HE). At least three views of each specimen were selected from each group to observe the pathological changes in the jejunum and ileum, and a comprehensive score was given for mucosal damage and the extent of lesions.

[0095] 3. Test Results

[0096] 3.1 Results of stomach volume, gastric emptying, intestinal propulsion, and number of intestinal segments in rats

[0097] Table 2 shows that, compared with the normal group, the model group had a significantly larger stomach volume and significantly lower intestinal propulsion rate and number of intestinal segments, indicating severe gastric distension and insufficient gastrointestinal motility in the model mice, and the rat model was successfully established. Compared with the model group, the *Hemiberlesia lataniae* extract group (Examples 1-3) significantly reduced gastric distension and increased gastric emptying rate, small intestinal propulsion rate, and number of intestinal segments, with effects comparable to the *Magnolia officinalis* gas-relieving compound group. The metoclopramide group showed poor or even no effect on gastric distension, gastric emptying rate, intestinal propulsion rate, and number of intestinal segments in postoperative paralytic ileus rats, far lower than the *Hemiberlesia lataniae* extract group and the *Magnolia officinalis* gas-relieving compound group. This indicates that simple prokinetic drugs are not ideal for postoperative paralytic ileus. The *Hemiberlesia lataniae* extract obtained by the preparation method of this invention has a good therapeutic effect on postoperative paralytic ileus, and this difference is related to the more complex pathogenesis of postoperative paralytic ileus.

[0098] Table 2. Results of the rat postoperative ileus animal model

[0099] Stomach volume (mL) Gastric emptying rate (%) Small intestinal propulsion rate (%) Intestinal segment values normal control group 3.97±1.74 79.01±6.37 75.18±11.1 5.44±1.74 Model group <![CDATA[11.30±3.34 ## ]]> 80.80±7.73 <![CDATA[21.70±13.33 ## ]]> <![CDATA[2.40±1.07 ## ]]> Sham surgery group <![CDATA[5.18±2.70 ** ]]> 84.83±7.91 <![CDATA[72.22±13.44 ** ]]> <![CDATA[4.80±1.69 ** ]]> Magnolia officinalis exhaust mixture <![CDATA[7.59±3.94 * ]]> 83.77±4.13 <![CDATA[75.43±25.24 ** ]]> <![CDATA[5.40±2.76 ** ]]> Example 1 Group <![CDATA[6.78±3.55 * ]]> <![CDATA[89.48±4.28 ** ]]> <![CDATA[67.09±16.91 ** ]]> <![CDATA[5.20±2.25 ** ]]> Example 2 group <![CDATA[6.47±2.82 ** ]]> <![CDATA[90.87±2.25 ** ]]> <![CDATA[71.03±16.09 ** ]]> <![CDATA[5.70±2.00 ** <!-- 6 -->]]> Example 3 Group <![CDATA[6.25±2.81 ** ]]> <![CDATA[89.30±2.65 ** ]]> <![CDATA[70.33±11.47 * ]]> <![CDATA[5.30±1.95 ** ]]> Metoclopramide group 8.90±2.84 81.33±2.81 <![CDATA[41.53±16.0 ** ]]> 2.80±1.14

[0100] Note: # P < 0.05 ## P < 0.01, model group vs. normal group; * P < 0.05 ** P < 0.01 Treatment group vs. model group; mean ± SD, n = 9–12.

[0101] 3.2 Pathological and histological observation

[0102] HE staining was used to observe the morphology of jejunal tissue in each group of rats. The results showed that the jejunal mucosa structure was intact in the normal control group, with complete intestinal villi, clearly visible outlines, and a tight, orderly arrangement. The villi epithelial cells were continuous and intact. Compared with the control group, the jejunal tissue of the model group showed extensive shedding of intestinal villi epithelial cells, exposure of the lamina propria, separation of intestinal villi epithelial cells from the lamina propria, shortened villi, structural damage, and a significantly loose and disordered arrangement. Damage to the basal layer of the crypts was observed, with hemorrhage and inflammatory cell infiltration. Compared with the model group, the degree of mucosal damage was significantly reduced in the treatment groups of Examples 1 and 2, the length of intestinal villi was significantly increased, the villi tips were slightly ruptured, and the arrangement tended to be regular and orderly.

[0103] Test Example 2: Pharmacodynamic Model Experiment of Postoperative Gastrointestinal Paralysis in Rabbits

[0104] 1. Model Establishment

[0105] New Zealand rabbits were fasted but allowed to drink water for 24 hours, anesthetized by intravenous injection of sodium pentobarbital, routinely disinfected abdominally, incised in the midline of the lower abdomen, the colon 5 cm away from the ileocecal junction was taken out and resected, and the abdomen was closed after intestinal end-to-end anastomosis. The blank group underwent sham operation, that is, sutured after laparotomy. There were 24 animals in each group, and bowel sounds and the time of first defecation of 12 of them were observed.

[0106] 2. Test Grouping and Drug Administration

[0107] New Zealand rabbits were purchased from Shanghai Slack Experimental Animal Co., Ltd. (License No.: SCXK (Shanghai) 2022-0004) and were routinely raised in the Experimental Animal Center of Nanjing University of Chinese Medicine.

[0108] New Zealand rabbits were randomly divided into a control group (control), a model group (model), a Houpu Exhaust Mixture group (P), a metoclopramide group (W), and three examples according to sex and body weight. Intragastric administration was carried out 3, 6, and 12 hours after surgery, and the intragastric dose was equal each time.

[0109] Table 3.

[0110] test substance Dosage physiological saline - physiological saline - Magnolia officinalis decomposition compound 4.64 mg / kg Metoclopramide group 4.15 mg / kg TSZ Iron Broom Extract 0.67g / kg

[0111] 3. Detection

[0112] Recovery of bowel sounds and time of first defecation after surgery: Starting from 6 hours after the surgery, bowel sounds of the animals were recorded once every 1 hour, and the time of first defecation was determined according to video recording.

[0113] 4. Results

[0114] As can be seen from Table 4, in rabbit surgery, compared with the model group, there were extremely significant differences (P < 0.01) in the total bowel sound appearance time and the time of first defecation of New Zealand rabbits in the Lespedeza cuneata extract groups (Examples 1-3 groups) and the Houpu Exhaust Mixture group, and there were no significant differences among the groups, indicating that: Lespedeza cuneata extract can shorten the total bowel sound appearance time and the time of first defecation after surgery and improve postoperative intestinal paralysis.

[0115] At the same time, the metoclopramide group did not significantly improve the total bowel sound appearance time of New Zealand rabbits, and the time of first defecation was not much different from that of the model group, indicating that simple gastrokinetic drugs have an unsatisfactory effect on postoperative intestinal paralysis.

[0116] The above results indicate that the iron broom extract obtained by the preparation method of the present invention has a good therapeutic effect on postoperative paralytic ileus, and this difference is related to the more complex pathogenesis of postoperative paralytic ileus.

[0117] Table 4. Animal efficacy model of postoperative gastrointestinal paralysis in rabbits

[0118]

[0119] Note: # P < 0.05 ## P < 0.01, model group vs. normal group; * P < 0.05 ** P < 0.01 Treatment group vs. model group; mean ± SD, n = 9–12.

[0120] In summary, the iron broom extract of the present invention has a significant therapeutic effect on postoperative ileus (POI).

[0121] Based on the above experiments, the iron broom extract was further prepared into common dosage forms in this field, such as pills and granules. Preparation examples are as follows:

[0122] (1) Preparation of Kexiemin Pill 1

[0123] Weigh the prescribed amount of iron broom extract, pulverize, sieve, make into pills with water, coat, polish, and dry to obtain the final product.

[0124] (2) Preparation of Kexiemin Pill 2

[0125] Weigh the prescribed amount of iron broom extract, add dextrin, mix well, add starch slurry, sieve, make into pills with water, coat, polish, and dry to obtain the product.

[0126] (3) Preparation of Kexiemin Pill 3

[0127] Weigh out the prescribed amount of iron broom extract, add dextrin and microcrystalline cellulose, mix well, add starch slurry, sieve, make into pellets with water, coat, polish, and dry to obtain the product.

[0128] (4) Preparation of Kexiemin Granules 1

[0129] The preparation method of Kexiemin granules is as follows: take the prescribed amount of iron broom extract, crush, sieve, mix, granulate, and dry.

[0130] (5) Preparation of Kexiemin Granules 2

[0131] The preparation method of Kexiemin granules is as follows: take the prescribed amount of iron broom extract, crush it, sieve it, add sucrose, mix it well, granulate it, and dry it.

[0132] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. Application of iron broom in the preparation of drugs for the prevention and / or treatment of postoperative ileus.

2. The application according to claim 1, characterized in that, The postoperative ileus is ileus caused by surgical procedures.

3. The application according to claim 1, characterized in that, The symptoms of postoperative ileus include at least one of the following: impaired gastrointestinal motility, nausea, vomiting, abdominal pain, cessation of flatus, and cessation of defecation.

4. The application of *Hemiberlesia lataniae* extract in the preparation of drugs for the prevention and / or treatment of postoperative paralytic ileus, wherein the preparation method of *Hemiberlesia lataniae* extract includes the following steps: (1) Extract the iron broom herb with water 2-4 times and combine the extracts to obtain the extract; (2) Concentrate the extract obtained in step (1) to obtain a concentrated solution; (3) The concentrate obtained in step (2) is subjected to alcohol precipitation and dried to obtain the iron broom extract.

5. The application according to claim 4, characterized in that, The postoperative ileus is ileus caused by surgical procedures.

6. The application according to claim 4, characterized in that, The symptoms of postoperative ileus include at least one of the following: impaired gastrointestinal motility, nausea, vomiting, abdominal pain, cessation of flatus, and cessation of defecation.

7. The application according to claim 4, characterized in that, In step (1), the water extraction is performed as follows: for the first extraction, add 5-10 times the mass of water, extract for 1-3 hours, and at a temperature of 95-100℃; for the second extraction, add 4-8 times the mass of water, extract for 1-2 hours, and at a temperature of 95-100℃.

8. The application according to claim 4, characterized in that, The concentration is either evaporative concentration or double-effect concentration.

9. The application according to claim 8, characterized in that, The conditions for the dual-effect concentration are as follows: Steam pressure: 0.05~0.15MPa; First-effect vacuum: -0.06~-0.09MPa; First-effect concentration temperature: 60~85℃; Concentration time: 100-150 min; Relative density of concentrate: 1.0-1.1; Second-effect vacuum: -0.06~-0.09MPa; Second-effect concentration temperature: 60~85℃; Concentration time: 40-80 min; Relative density of concentrate: 1.2-1.

4.

10. The application according to claim 4, characterized in that, In step (3), the alcohol precipitation specifically involves adding ethanol to the concentrate to achieve an ethanol content of 50-70%, mixing thoroughly, and allowing it to stand.

11. The use of Kexiemin pills or Kexiemin granules in the preparation of drugs for the prevention and / or treatment of postoperative paralytic ileus, characterized in that the active ingredient of the Kexiemin pills or Kexiemin granules is the iron broom extract as described in claim 4.

12. The application according to claim 11, characterized in that, The postoperative ileus is ileus caused by surgical procedures.

13. The application according to claim 11, characterized in that, The symptoms of postoperative ileus include at least one of the following: impaired gastrointestinal motility, nausea, vomiting, abdominal pain, cessation of flatus, and cessation of defecation.

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