Application of Chinese knotweed rhizome and aloe bowel-relaxing capsule in preparation of medicine for preventing or treating postoperative enteroparalysis

Abstract

The invention provides a novel application of a traditional Chinese medicine composition prepared by taking polygonum multiflorum, aloe, semen cassiae, fructus lycii, colla corii asini, ginseng, rhizoma atractylodis macrocephalae and fructus aurantii immaturus as main components, and particularly relates to an application of the traditional Chinese medicine composition in preparation of a medicine for preventing or treating postoperative intestinal paralysis. Research results show that the traditional Chinese medicine composition provided by the invention can effectively improve the postoperative intestinal peristalsis function and intestinal inflammation and tissue damage caused by postoperative intestinal paralysis. The traditional Chinese medicine composition is exact in curative effect and safe in components, and has wide application prospects and positive clinical significance.

Description

Technical Field

[0001] The invention belongs to the field of medicine and relates to use of a traditional Chinese medicine composition in preparing a drug for preventing or treating postoperative intestinal paralysis. Specifically, the traditional Chinese medicine composition is the marketed drug Shouhui Tongbian Capsule, which is a compound traditional Chinese medicine preparation made by extracting and processing eight traditional Chinese medicines, namely, Polygonum multiflorum, aloe, Cassia seed, wolfberry fruit, donkey-hide gelatin, ginseng, Atractylodes macrocephala, and Citrus aurantium. Background Art

[0002] Postoperative ileus (POI) refers to a type of disease in which temporary gastrointestinal motility disorders caused by non-mechanical reasons after abdominal surgery lead to ineffective emptying of intestinal contents and / or inability to eat orally, mainly manifested by abdominal pain, bloating, vomiting, and anal gas and defecation disorders. If not treated in time, the intestinal barrier will be damaged, the systemic inflammatory response will be aggravated, and various postoperative complications such as enterogenic infection and multiple organ failure will be caused, which will prolong the hospital stay, increase the cost of hospitalization, and reduce the quality of life of patients. Postoperative ileus is a common surgical problem. Almost all abdominal surgeries will have symptoms of postoperative gastrointestinal dysfunction to varying degrees. At present, the mechanism leading to POI has not been clearly defined, involving multiple mechanisms. The use of anesthetics, external environmental stimulation, abdominal inflammation, and preoperative intestinal preparation are all important factors affecting the occurrence of postoperative ileus. Anesthesia and opioids immediately after surgery can cause POI. Opioids are usually used as postoperative analgesics to activate μ-opioid receptors, reduce the release of acetylcholine, and inhibit gastrointestinal motility. The recovery time of POI directly affects the patient's clinical outcome and hospitalization costs. Any single drug or treatment measure cannot play a significant role in prevention and treatment. Therefore, actively exploring the pathogenesis and effective treatment measures is of great clinical significance.

[0003] Shouhui Tongbian Capsule is composed of Polygonum multiflorum, aloe, Cassia seed, donkey-hide gelatin, wolfberry, ginseng, Atractylodes macrocephala, and Citrus aurantium. Ginseng in the formula greatly replenishes vital energy and promotes the production of body fluid; aloe clears liver heat; Polygonum multiflorum and donkey-hide gelatin nourish yin and moisten dryness, nourish blood and moisten the intestines; Cassia seed, wolfberry, and Atractylodes macrocephala purge heat and promote defecation, replenish qi, nourish yin and moisten the intestines; Citrus aurantium breaks up qi and eliminates accumulation, and guides the meridians into medicine; the whole formula nourishes yin and replenishes qi, and has both tonifying and purging effects, and can improve clinical symptoms such as difficulty in defecation in patients with functional constipation by regulating gastrointestinal hormones. Chinese patent CN100453105C discloses a composition with laxative, detoxifying, weight loss and lipid-lowering functions and a preparation method thereof, the composition is prepared from a Chinese medicine prescription of eight flavors of Polygonum multiflorum, Aloe, Cassia seed, Lycium barbarum, donkey-hide gelatin, Ginseng, Atractylodes macrocephala, and Citrus aurantium, and can be used to treat functional constipation; Chinese patent CN106124685A discloses a quality detection method for Shouhui Tongbian Capsule, a Chinese patent medicine for treating constipation; Chinese patent CN111228389A discloses a use of a Chinese medicine composition, specifically discloses the use of Shouhui Tongbian Capsule in the preparation of a drug for preventing and treating abdominal distension. However, there is no report on the use of Shouhui Tongbian Capsule in improving POI. Summary of the invention

[0004] The invention provides use of a traditional Chinese medicine composition in preparing a drug for preventing or treating postoperative intestinal paralysis. The traditional Chinese medicine composition is prepared from polygonum multiflorum, aloe, cassia seed, wolfberry fruit, donkey-hide gelatin, ginseng, atractylodes macrocephala and immature bitter orange as main ingredients.

[0005] Furthermore, the Chinese medicine composition is prepared from the following weight portions of Polygonum multiflorum, aloe, Cassia seed, Lycium barbarum, donkey-hide gelatin, ginseng, Atractylodes macrocephala and Citrus aurantium as main ingredients:

[0006] Polygonum multiflorum 60-150 weight parts Aloe 100-200 weight parts Cassia seed 80-180 weight parts

[0007] 30-150 parts by weight of wolfberry 30-150 parts by weight of donkey hide gelatin 20-100 parts by weight of ginseng

[0008] Atractylodes macrocephala 20-100 parts by weight, Citrus aurantium 50-200 parts by weight.

[0009] Furthermore, the Chinese medicine composition is prepared with the following weight portions of Polygonum multiflorum, aloe, Cassia seed, Lycium barbarum, donkey-hide gelatin, ginseng, Atractylodes macrocephala and Citrus aurantium as main ingredients:

[0010] 120 parts by weight of Polygonum multiflorum 160 parts by weight of Aloe Vera 140 parts by weight of Cassia seed

[0011] 75 parts by weight of wolfberry 75 parts by weight of donkey hide gelatin 50 parts by weight of ginseng

[0012] 50 parts by weight of Atractylodes macrocephala and 120 parts by weight of Citrus aurantium.

[0013] The Chinese medicine composition provided by the present invention can be added with pharmaceutically acceptable excipients to prepare a clinically acceptable dosage form, such as an oral preparation or an injection preparation.

[0014] Furthermore, the dosage form can be pills, tablets, granules, capsules, oral liquids, suspensions, mixtures, powders, or injections.

[0015] The present invention also provides use of the traditional Chinese medicine composition in preparing a medicine for improving postoperative intestinal motility function.

[0016] The present invention also provides use of the traditional Chinese medicine composition in preparing a medicine for improving postoperative intestinal tissue damage.

[0017] The present invention also provides use of the traditional Chinese medicine composition in preparing a medicine for improving postoperative intestinal inflammation.

[0018] The medicine described in the present invention is Shouhui Tongbian Capsule.

[0019] The present invention is a new use development for the existing product of Runan Pharmaceutical Group, Shouhui Tongbian Capsule. The patent of Shouhui Tongbian Capsule is CN100453105C, and the invention name is "A composition with laxative, detoxification, weight loss and lipid reduction functions and preparation method" has been authorized. The Chinese medicine composition of the present invention is prepared according to the preparation or extraction method in patent CN100453105C.

[0020] The present invention has achieved the following beneficial technical effects:

[0021] The POI mouse model was established by using classic small intestinal interference surgery, and it was observed that the intestinal motility of POI mice was significantly weakened. After intervention with Mosapride Capsules, the intestinal motility of POI mice was significantly improved. Both high and low doses of Shouhui Tongbian Capsules significantly improved the intestinal motility of POI mice, with no significant difference compared with Mosapride Capsules, indicating that Shouhui Tongbian Capsules can effectively improve postoperative intestinal paralysis. The neutrophils and lymphocytes in the lamina propria of the small intestinal mucosa of POI mice increased, accompanied by congestion, edema of connective tissue and other pathological phenomena, while the intestinal tissue damage, mucosal congestion, edema, inflammatory cell infiltration, etc. of mice in the high and low doses of Shouhui Tongbian Capsules group and Mosapride group were significantly alleviated, indicating that Shouhui Tongbian Capsules have a good improvement effect on intestinal inflammation and tissue damage in postoperative intestinal paralysis. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The total length of the small intestine and the distance from the pylorus to the front of the ink were measured in each group of mice;

[0023] Figure 2 is the small intestinal propulsion rate of mice in each group;

[0024] Figure 3Intestinal tissue pathological sections of each group of mice.

[0025] Note: *** indicates P < 0.001 compared with Control; ## indicates P < 0.01 compared with the POI group, and indicates P < 0.001 compared with the POI group. Detailed implementation manners

[0026] The present invention will be further described in detail below in conjunction with specific embodiments. The following embodiments give detailed implementation manners and specific operation processes to illustrate the technical solutions of the present invention, but do not limit the protection scope of the present invention. Those of ordinary skill in the art who modify or equivalently replace the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention still fall within the protection scope of the present invention.

[0027] 1. Experimental animals

[0028] Thirty male C57BL / 6J mice (SPF grade), weighing 20 - 22 grams, were purchased from Henan Sk贝斯 Biotechnology Co., Ltd., with the license number SCXK(Yu)2020 - 0005. The animals were housed in the Animal Experiment Center of Jiangsu Provincial Hospital of Traditional Chinese Medicine and fed a standard experimental diet.

[0029] 2. Drugs and reagents

[0030] Shouhui Laxative Capsule (Lunan Hepu Pharmaceutical Co., Ltd., national drug approval number Z20150041);

[0031] Mosapride Citrate Capsule (Shanghai上药信谊药厂有限公司, national drug approval number H20051719);

[0032] Isoflurane (Reword Life Science Co., Ltd., 22061101);

[0033] Absolute ethanol (Sinopharm Chemical Reagent Co., Ltd., 100092683);

[0034] Xylene (Sinopharm Chemical Reagent Co., Ltd., 10023418);

[0035] Environmentally friendly dewaxing solution (Servicebio, G1128);

[0036] Universal tissue fixative (Servicebio, G1101);

[0037] HE staining solution set (Servicebio, G1003);

[0038] Neutral gum (Sinopharm Chemical Reagent Co., Ltd., 10004160);

[0039] 3. Experimental process

[0040] 3.1 Animal grouping, modeling and drug administration

[0041] The mice were randomly divided into control group, POI group, mosapride group (MSBL), Shouhui Tongbian capsule low-dose group (SHTB-L) and Shouhui Tongbian capsule high-dose group (SHTB-H), with 6 mice in each group. The mice in each group were fasted for 12 hours with free drinking water before the experiment.

[0042] The mouse POI model was established by classic small intestinal interference: the mice were anesthetized by inhalation of isoflurane and placed supine on the operating table, depilated and disinfected; the abdominal cavity was opened along the linea alba, and a sterile gauze towel was placed on the mouse abdomen. Two sterile cotton swabs moistened with normal saline were used to gently remove the small intestinal segment from the abdominal cavity and place it on the gauze, and then rolled back and forth from the proximal jejunum (Treitz ligament) to the terminal ileum and gently squeezed for 15 minutes; after the stimulation, the small intestine was returned to the abdominal cavity, and the abdominal cavity was closed by double-layer continuous suture. After the operation, the Control group and the POI group were given an equal dose of normal saline by gavage, the MSBL group was given a solution of mosapride capsules (0.195 mg / mL), and the SHTB-L group and the SHTB-H group were given a solution of 0.135 g / mL and 0.27 g / mL of Shouhui Tongbian capsules, respectively, with a volume of 10 ml / kg, once a day, for 2 consecutive days.

[0043] 3.2 Detection indicators

[0044] 3.2.1 Detection of intestinal motility function of mice in each group

[0045] 36 hours after the end of the administration, the mice in each group were fasted for 12 hours, and the mice in each group were gavaged with India ink (1 mL / 100 g). After 20 minutes, the mice were anesthetized by intraperitoneal injection of isoflurane (0.1 mL / 10 g), and the mice were killed by cervical dislocation after orbital blood sampling. The intestinal tube from the pylorus to the ileocecal part was obtained by laparotomy, and the total length of the small intestine and the distance from the pylorus to the front end of the ink were measured flat, and the small intestine propulsion rate was calculated. Small intestine propulsion rate (%) = ink propulsion distance in the small intestine / total length of the small intestine × 100%.

[0046] 3.2.2 Histopathological observation

[0047] A section of ileum near the cecum was fixed in 4% formaldehyde solution, dehydrated with gradient ethanol, embedded in paraffin, and sliced. It was then stained with hematoxylin and eosin (HE), and finally the pathological changes of intestinal tissue were observed under an optical microscope.

[0048] 3.3 Statistical analysis

[0049] GraphPadPrism 8.0 software was used for statistical analysis and graph drawing. All data are expressed as mean ± standard deviation The data were expressed in the form of . One-way analysis of variance was used for comparison among the groups. P < 0.05 was considered statistically significant.

[0050] 4 Results and conclusions

[0051] 4.1 Effect of Shouhui Tongbian Capsule on Intestinal Peristalsis Function of POI Mice

[0052] like Figure 1 and Figure 2 As shown in the figure, compared with the Control group, the intestinal ink propulsion rate of mice in the POI group was significantly reduced 48 hours after surgery (P<0.001), indicating that the model was successfully established. The small intestinal propulsion rate of mice in the MSBL group was significantly increased after intervention with Mosapride Capsules (P<0.001); compared with the POI group, the intestinal ink propulsion rate of mice in the SHTB-L (P<0.01) and SHTB-H groups (P<0.001) was significantly increased, and there was no statistically significant difference compared with the MSBL group. The above experimental results show that Shouhui Tongbian Capsules can effectively improve postoperative intestinal paralysis.

[0053] 4.2 Effect of Shouhui Tongbian Capsule on Intestinal Histopathology of POI Mice

[0054] like Figure 3 As shown in the figure, the epithelial cells of the small intestinal tissue of the Control group were intact, with a small amount of inflammatory cell infiltration, and no congestion and edema. Compared with the Control group, the neutrophils and lymphocytes in the lamina propria of the small intestinal tissue of the mice in the POI group increased, and the epithelial cells reactively proliferated, indicating changes in acute injury. At the same time, the epithelial cell nuclei became larger, and subserous fibrous connective tissue edema, vascular dilation, congestion and bleeding were observed on some serosal surfaces; similar to the MSBL group, the intestinal tissue damage, mucosal congestion, edema, etc. of the mice in the SHTB-L and SHTB-H groups were significantly alleviated, and the infiltration of inflammatory cells was significantly reduced. The above suggests that Shouhui Tongbian Capsule has a good improvement effect on intestinal inflammation and tissue damage in postoperative intestinal paralysis.

Claims

1. Use of a Chinese medicine composition in preparing a drug for preventing or treating postoperative intestinal paralysis, wherein the Chinese medicine composition is prepared with Polygonum multiflorum, aloe, Cassia seed, Lycium barbarum, donkey-hide gelatin, ginseng, Atractylodes macrocephala and Citrus aurantium as main ingredients.

2. The use according to claim 1, characterized in that The Chinese medicine composition is prepared from the following weight portions of Polygonum multiflorum, aloe, Cassia seed, Lycium barbarum, donkey-hide gelatin, ginseng, Atractylodes macrocephala and Citrus aurantium as main ingredients: Polygonum multiflorum 60-150 weight parts Aloe 100-200 weight parts Cassia seed 80-180 weight parts 30-150 parts by weight of wolfberry 30-150 parts by weight of donkey hide gelatin 20-100 parts by weight of ginseng Atractylodes macrocephala 20-100 parts by weight, Citrus aurantium 50-200 parts by weight.

3. The use according to claim 2, characterized in that The Chinese medicine composition is prepared from the following weight portions of Polygonum multiflorum, aloe, Cassia seed, Lycium barbarum, donkey-hide gelatin, ginseng, Atractylodes macrocephala and Citrus aurantium as main ingredients: 120 parts by weight of Polygonum multiflorum 160 parts by weight of Aloe Vera 140 parts by weight of Cassia seed 75 parts by weight of wolfberry 75 parts by weight of donkey hide gelatin 50 parts by weight of ginseng 50 parts by weight of Atractylodes macrocephala and 120 parts by weight of Citrus aurantium.

4. The use according to any one of claims 1 to 3, characterized in that The traditional Chinese medicine composition can be added with pharmaceutically acceptable excipients to prepare a clinically acceptable dosage form.

5. The use according to claim 4, characterized in that The dosage form can be an oral preparation or an injection preparation.

6. The use according to claim 5, characterized in that The dosage forms include, but are not limited to, pills, tablets, granules, capsules, oral solutions, suspensions, mixtures, powders, and injections.

7. The use according to claim 1, characterized in that The Chinese medicine composition is used in preparing a medicine for improving postoperative intestinal motility function.

8. The use according to claim 1, characterized in that The Chinese medicine composition is used in preparing a medicine for improving postoperative intestinal tissue damage.

9. The use according to claim 1, characterized in that The Chinese medicine composition is used in preparing a drug for improving postoperative intestinal inflammation.

10. The use according to claim 1, characterized in that The medicine is Shouhui laxative capsule.

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