CN112043718A - Application of magnesium isoglycyrrhizinate in preparing medicine for treating colitis - Google Patents
Application of magnesium isoglycyrrhizinate in preparing medicine for treating colitis Download PDFInfo
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- CN112043718A CN112043718A CN202011020718.9A CN202011020718A CN112043718A CN 112043718 A CN112043718 A CN 112043718A CN 202011020718 A CN202011020718 A CN 202011020718A CN 112043718 A CN112043718 A CN 112043718A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Abstract
The invention belongs to the technical field of pharmacy. The application of magnesium isoglycyrrhizinate in preparing the medicament for treating colitis: in a disease model of acute and chronic enteritis of mice induced by dextran sodium sulfate DSS, the magnesium isoglycyrrhizinate can effectively improve the conditions of weight loss, diarrhea, hematochezia and colon shortening of the mice, reduce inflammatory cell infiltration and the expression level of inflammatory factors in the colon of the mice, maintain the integrity of an intestinal epithelial barrier, increase connexin Zo-1, occludin and E-cadherin, reduce the expression level of Claudin-2 and reduce fibrosis caused by colitis. The invention discovers that the magnesium isoglycyrrhizinate can treat the colitis for the first time, increases the clinical application of the magnesium isoglycyrrhizinate and has remarkable popularization value.
Description
Technical Field
The invention relates to a new application of magnesium isoglycyrrhizinate, in particular to an application of magnesium isoglycyrrhizinate in a medicine for treating colitis.
Background
Inflammatory bowel disease is a chronic incurable disease and has the characteristics of complex etiology, easy relapse and difficult cure. Inflammatory bowel disease is classified into ulcerative colitis and crohn's disease. The clinical features of colitis are repeated diarrhea and ulcer accompanied by inflammatory cell infiltration and secretion of cytokines such as IL-6 and TNF-alpha. At present, clinical drug treatment schemes are not many, the existing drugs have large side effects, and a great part of patients do not respond in clinical treatment.
The magnesium isoglycyrrhizinate injection is developed as a liver protection drug, and the research on the compound mainly focuses on the aspect of chronic viral hepatitis. The unique pharmacological action for treating the colitis is not reported so far. The invention discovers that the magnesium isoglycyrrhizinate has obvious improvement effect on a mouse colitis model for the first time. The magnesium isoglycyrrhizinate has the following structural formula:
disclosure of Invention
The purpose of the invention is as follows:
the invention provides a new application of magnesium isoglycyrrhizinate.
The technical scheme is as follows:
use of magnesium isoglycyrrhizinate in preparing medicine for treating colitis is provided.
Advantageous effects
The invention discovers that the magnesium isoglycyrrhizinate can treat the colitis for the first time, increases the clinical application of the magnesium isoglycyrrhizinate and has remarkable popularization value.
Specifically, the method comprises the following steps:
there are many animal models of colitis, such as drug-induced acute enteritis model and chronic enteritis model, bacteria-induced enteritis model, gene mutation and transgenic model. The DSS-induced colitis model in mice has been widely used in the study of human colitis in recent years because of its simple preparation method and similar pathogenesis to human colitis.
The invention adopts a mouse colitis model induced by dextran sodium sulfate DSS, and experimental results show that subcutaneous injection of magnesium isoglycyrrhizinate (2.5mg/kg, 5mg/kg) can obviously inhibit the weight loss of mice, reduce Disease Activity Index (DAI) scores, inhibit the shortening of colon length, reduce the expression levels of inflammatory factors IL-1 beta, IL-6, IL-17A, IFN-gamma and TNF-alpha in colon tissues, reduce intestinal permeability, increase the expression of connexin ZO-1 and E-cadherin, and maintain the intestinal epithelial barrier function.
The results indicate that the magnesium isoglycyrrhizinate injection can improve the relevant symptoms of the colitis of the mice, so the magnesium isoglycyrrhizinate injection can be applied to the treatment medicines of the colitis.
Drawings
FIG. 1 shows the effect of magnesium isoglycyrrhizinate injection on DSS-induced acute colitis in mice. The mice were randomly divided into 5 groups, a normal group (Control group), a model group (DSS group), and low, medium, and high doses of magnesium isoglycyrrhizinate (1.25mg/kg, 2.5mg/kg, 5 mg/kg). Mice were fed with 2.5% DSS for 7 days in both the model and the dosed groups, followed by 2 days of water recovery. The administration group was administered intraperitoneally once a day, 200. mu.l each time, in a dose. Thereafter, the body weight of the mice was recorded daily and Disease Activity Index (DAI) scores were performed. Mice were sacrificed on day 9. (A) Body weight change (percentage of original body weight). (B) Clinical disease activity index of mice. (C) 2.5% DSS induced colon morphology on day 9 of the enteritis model. (D) The length of the colon. Results are expressed as mean ± standard deviation. Data analysis was performed using the Unpreared Student's t-test method: p <0.05, x: p <0.01vs DSS.
FIG. 2 shows the effect of magnesium isoglycyrrhizinate injection on DSS-induced acute colitis in mice. The mice were randomly divided into 5 groups, a normal group (Control group), a model group (DSS group), and low, medium, and high doses of magnesium isoglycyrrhizinate (1.25mg/kg, 2.5mg/kg, 5 mg/kg). Mice were fed with 2.5% DSS for 7 days in both the model and the dosed groups, followed by 2 days of water recovery. The administration group was administered intraperitoneally once a day, 200. mu.l each time, in a dose. Thereafter, the body weight of the mice was recorded daily and a Disease Activity Index (DAI) score was performed, and the mice were sacrificed at day 9. DSS-induced mRNA expression of inflammatory factors (IL-1 beta, IL-6, IL-17, TNF-alpha, IFN-gamma) in colon tissue of mice. Data analysis was performed using the Unpreared Student's t-test method: p <0.05, x: p <0.01vs DSS.
FIG. 3 shows the effect of magnesium isoglycyrrhizinate injection on intestinal barrier of DSS-induced acute colitis in mice. The mice were randomly divided into 5 groups, a normal group (Control group), a model group (DSS group), and low, medium, and high doses of magnesium isoglycyrrhizinate (1.25mg/kg, 2.5mg/kg, 5 mg/kg). Mice were fed with 2.5% DSS for 7 days in both the model and the dosed groups, followed by 2 days of water recovery. The administration group was administered intraperitoneally once a day, 200. mu.l each time, in a dose. Thereafter, the body weight of the mice was recorded daily and a Disease Activity Index (DAI) score was performed, and the mice were sacrificed at day 9. (A) FITC-Dextran intestinal permeability assay. (B) mRNA expression of tissue ligation indicator (claudin, occludin, E-cadherin, ZO-1). Results are expressed as mean ± standard deviation; *: p <0.05, x: p <0.01vs DSS (Student's-t test).
FIG. 4 shows the effect of magnesium isoglycyrrhizinate injection on DSS-induced chronic colitis in mice. The mice were randomly divided into 3 groups, a normal group (Control group), a model group (DSS group), and a magnesium isoglycyrrhizinate injection of 5 mg/kg. Mice were fed with 2.5% DSS for 7 days in both the model and the dosed groups, followed by 2 days of water recovery. The administration group was administered intraperitoneally once a day, 200. mu.l each time, in a dose. Thereafter, the body weight of the mice was recorded daily and a Disease Activity Index (DAI) score was performed, and the mice were sacrificed at day 9. (A) Body weight change (percentage of original body weight). (B) Clinical disease activity index of mice. (C) 2.5% DSS induced colon morphology on day 9 of the enteritis model. (D) The length of the colon. Results are expressed as mean ± standard deviation; *: p <0.05, x: p <0.01vs DSS (Student's-t test).
FIG. 5 Effect of magnesium isoglycyrrhizinate injection on DSS-induced chronic colitis model in mice. The mice were randomly divided into 3 groups, a normal group (Control group), a model group (DSS group), and a magnesium isoglycyrrhizinate injection of 5 mg/kg. Mice were fed with 2.5% DSS for 7 days in both the model and the dosed groups, followed by 2 days of water recovery. The administration group was administered intraperitoneally once a day, 200. mu.l each time, in a dose. Thereafter, the body weight of the mice was recorded daily and a Disease Activity Index (DAI) score was performed, and the mice were sacrificed at day 9. DSS-induced mRNA expression of inflammatory factors (IL-1 beta, IL-6, IL-17, TNF-alpha, IFN-gamma) in colon tissue of mice. Results are expressed as mean ± standard deviation; *: p <0.05, x: p <0.01vs DSS (Student's-t test).
FIG. 6 shows the effect of magnesium isoglycyrrhizinate injection on intestinal barrier of DSS-induced chronic colitis in mice. The mice were randomly divided into 3 groups, a normal group (Control group), a model group (DSS group), and a magnesium isoglycyrrhizinate injection of 5 mg/kg. Mice were fed with 2.5% DSS for 7 days in both the model and the dosed groups, followed by 2 days of water recovery. The administration group was administered intraperitoneally once a day, 200. mu.l each time, in a dose. Thereafter, the body weight of the mice was recorded daily and a Disease Activity Index (DAI) score was performed, and the mice were sacrificed at day 9. mRNA expression of tissue ligation indicator (claudin, occludin, E-cadherin, ZO-1). Results are expressed as mean ± standard deviation; *: p <0.05, x: p <0.01vs DSS (Student's-t test).
Detailed Description
DSS was purchased from MP corporation; the magnesium isoglycyrrhizinate injection is purchased from Jiangsu Zhengda Tianqing pharmaceutical industry GmbH.
Example 1
1. Pharmacological experiment of magnesium isoglycyrrhizinate injection: DSS-induced mouse colitis model [1]
C57BL/6 female mice are taken, aged 6-8 weeks and 22-24g are bred in an SPF animal room at 21 +/-2 ℃, freely drunk by drinking water and taken, and are alternated day and night for 12 h. Mice were randomly divided into 5 groups, a normal group (Sham group), a model group (DSS group), and low, medium, and high dose groups (1.25mg/kg, 2.5mg/kg, 5mg/kg) of Magnesium Isoglycyrrhizinate (MIG). Mice were fed with 2.5% DSS for 7 days in both the model and the dosed groups, followed by 2 days of water recovery. The administration group was administered intraperitoneally once a day, 200. mu.l each time, in a dose. Thereafter, the body weight of the mice was recorded daily and a Disease Activity Index (DAI) score was performed, the mice were sacrificed at day 9, and then the length of the colon of the mice and histopathological sections thereof were observed to detect the expression level of inflammatory factors in the colon.
Pharmacological experiment result analysis of magnesium isoglycyrrhizinate injection
1) Magnesium isoglycyrrhizinate injection for relieving DSS-induced acute colitis in mice
As shown in fig. 1, the body weight of the model group (DSS group) was significantly reduced and the DAI score was significantly increased compared to the normal group (control group); magnesium Isoglycyrrhizinate (MIG) group (2.5mg/kg, 5mg/kg) significantly inhibited weight loss, increased DAI score and colon shortening in mice; the Magnesium Isoglycyrrhizinate (MIG)5mg/kg group showed a slower weight loss and a slower DAI increase, with a longer colon length.
As shown in FIG. 2, compared with the normal group, the expression levels of the inflammatory factors IL-1 beta, IL-6, IL-17A, IFN-gamma and TNF-alpha in the model group are obviously increased, and the expression of the inflammatory factors can be obviously reduced by administering the magnesium isoglycyrrhizinate group (2.5mg/kg, 5 mg/kg).
As shown in FIG. 3, compared with the normal group, the intestinal epithelial permeability of the model group is obviously increased, the expression of the connexin (ZO-1, occludin, E-cadherin) is obviously reduced, and the expression of claudin-2 is obviously increased; the magnesium isoglycyrrhizinate can obviously reduce the intestinal permeability and maintain the expression of connexin.
2) Magnesium isoglycyrrhizinate injection for relieving DSS-induced chronic colitis in mice
As shown in fig. 4, the body weight of the model group (DSS group) was significantly reduced and the DAI score was significantly increased compared to the normal group (control group); magnesium Isoglycyrrhizinate (MIG) group (5mg/kg) significantly inhibited weight loss, increased DAI score, and shortened colon in mice; the Magnesium Isoglycyrrhizinate (MIG)5mg/kg group showed a slower weight loss and a slower DAI increase, with a longer colon length.
As shown in FIG. 5, compared with the normal group, the expression levels of the inflammatory factors IL-1 beta, IL-6, IL-17A, IFN-gamma and TNF-alpha in the model group were significantly increased, and the administration of magnesium isoglycyrrhizinate (5mg/kg) all significantly reduced the expression of the inflammatory factors.
As shown in FIG. 6, the expression of connexin (ZO-1, occludin, E-cadherin) was significantly decreased and the expression of claudin-2 was significantly increased in the model group as compared with the normal group; the magnesium isoglycyrrhizinate can obviously reduce the intestinal permeability and maintain the expression of connexin.
[1]Guo W,Sun Y,Liu W,Wu X,Guo L,Cai P,et al.Small molecule-driven mitophagy-mediated NLRP3 inflammasome inhibition is responsible for the prevention of colitis-associated cancer.AUTOPHAGY 2014;10:972-85.
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Non-Patent Citations (2)
Title |
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余水岸等: "异甘草酸镁联合美沙拉嗪治疗轻中度克罗恩病的效果及分泌型磷脂酶A2与克罗恩病活动指数的相关性", 《广东医科大学学报》 * |
鲁占彪: "68例异甘草酸镁治疗溃疡性结肠炎效果观察", 《医学信息》 * |
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