CN115006416A - Application of astilbin in preparation of medicine for treating polyp - Google Patents
Application of astilbin in preparation of medicine for treating polyp Download PDFInfo
- Publication number
- CN115006416A CN115006416A CN202110242852.1A CN202110242852A CN115006416A CN 115006416 A CN115006416 A CN 115006416A CN 202110242852 A CN202110242852 A CN 202110242852A CN 115006416 A CN115006416 A CN 115006416A
- Authority
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- Prior art keywords
- polyps
- polyp
- astilbin
- use according
- gastrointestinal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Images
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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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
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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- A—HUMAN NECESSITIES
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
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Abstract
The invention relates to application of astilbin in preparation of a medicine for treating polyp. The astilbin of the invention can reduce the number of polyps formed in the intestinal segment in vivo and reduce the volume of the polyps. The astilbin of the invention has high safety and has application prospect in preparing medicines for treating or preventing polyp.
Description
Technical Field
The invention belongs to the field of medicines, relates to a new application of a natural product, and particularly relates to an application of astilbin in treating polypus.
Background
Polyps are neoplasms that grow out of the surface of human or mammalian tissue, and traditionally include adenomas, dysplasias, jagged lesions, and hamartomas, all of which are precancerous lesions in the classification of epithelial tumors. Histological classification can be classified into neoplastic and non-neoplastic polyps, including adenomatous polyps and non-adenomatous polyps. The pathological components include adenomatous, inflammatory, misstructured, hyperplastic, etc.
Adenomatous polyps include tubular adenomas, villous adenomas, and tubular villous adenomas. Polyp-shaped polyp; inflammatory polyps refer to polypoid granuloma caused by long-term chronic inflammation of mucosa, and are mostly seen in pathological intestinal tracts such as ulcerative colitis and chronic schistosomiasis; hyperplastic polyps, also called metaplastic polyps, occur mostly in the rectum, and although the number of polyps is large, there are no obvious symptoms and no tendency to cancerate. The characteristic of hamartoma polyps is represented by normal cell overgrowth and disorganization, and the currently known alimentary canal hamartoma polyposis is mainly Peutz-Jeghers syndrome, Cronkhite-Canada syndrome, juvenile polyposis and the like, wherein most of the alimentary canal hamartoma polyps are at risk of developing alimentary canal malignant tumors and (or) combining other malignant tumors.
Polyps are clinically manifested as inflammatory polyps, adenomatous polyps and certain syndromes of gastrointestinal polyposis. According to the diseased part, the disease can be divided into intestinal polyposis, uterine polyp, cervical polyp, laryngeal polyp, nasal polyp, large intestine polyp, stomach polyp, colon polyp, gallbladder polyp, etc. Although polyps are found in different sites, they are characterized by hyperproliferation of normal cells and disorganization, and are characterized clinically by multiple, difficult-to-heal, and possibly malignant changes.
Adenomatous polyps have active epithelial proliferation, often accompanied by intraepithelial neoplasia, and can become malignant adenocarcinomas. The incidence of adenomatous polyps increases with age, and increases significantly after age 50. It is generally considered that the rate of cancer is higher in polyps than in single-stage polyps, and the longer the adenoma is present, the higher the risk of canceration. Intestinal polyps, especially colorectal adenomatous polyps, are considered as precancerous lesions of colorectal cancer, surgical resection in different ways is the current main treatment, but the recurrence rate and the risk of canceration still exist. The reported medicaments for cooperating with operative treatment at present mainly comprise aspirin, non-steroidal anti-inflammatory drugs of celecoxib, metformin, folic acid and the like, but the problem of high recurrence rate after polypectomy cannot be thoroughly solved, so the existing treatment means cannot meet the clinical requirements yet.
Research on the etiology of intestinal polyps finds that smoking, drinking, high fat, high protein, low fiber and the like are risk factors in dietary habits. Along with the economic development of China, the change of dietary structures and the step-in aging of the polyps are realized, the incidence rate of the polyps is increased day by day, the requirements on the medicine for treating the polyps are stronger, and therefore, the research and the development of the medicine for effectively treating the polyps have important clinical significance.
Astilbin (ASB) is flavanonol glycoside compound with chemical name of (2R, 3R)5, 7, 3 ', 4' -tetrahydroxyflavanonol-3-O-alpha-L-rhamnopyranoside and chemical formula of C 21 H 22 O 11 . The molecular weight is 450.39, CAS number is 29838-67-3, and the structural formula is:
astilbin has wide pharmacological activity, and the existing pharmacological research shows that the astilbin has various pharmacological activities of immunosuppression, rejection reaction inhibition, anti-inflammation, analgesia, liver protection, kidney protection, antibiosis, diabetes and the like. Astilbin is widely available in plant sources, and is mainly present in various plants of Guttiferae, Hypericaceae, Juglandis, Liliaceae, Taxillaceae, Saxifragaceae, and Vitaceae, and can be separated from 26 plants of 15 genus of 12 families in the world at present. Based on the distribution and the accumulation of Chinese traditional medicine and plant resources, the engelhardtia roxburghiana, the glabrous greenbrier rhizome and the grape can be used as main sources of astilbin.
Disclosure of Invention
An object of the present invention is to provide astilbin and a preparation thereof for use in the prevention and or treatment of polyps in humans or mammals, preferably in the prevention and or treatment of polyps in humans. The prevention and or treatment of polyps in humans, including blocking or delaying postoperative recurrence of polyps.
The polyp in the present invention refers to a neoplasm growing on the mucosal surface of a human or a mammal. The polyps of the present invention include digestive tract polyps, endometrial polyps, cervical polyps, laryngeal polyps, nasal polyps, etc. according to the diseased part. The polyp refers to gastrointestinal polyposis syndrome. The gastrointestinal polyposis syndrome is Cronkhite-Canada syndrome.
Polyps according to the present invention are preferably gastrointestinal polyps, most preferably gastrointestinal polyps. Polyps of the digestive tract refer to single or multiple polyps occurring in the entire section of the digestive tract, including: esophageal polyp, gastric polyp, small intestinal polyp, large intestinal polyp (colon polyp, rectal polyp), anal polyp, gallbladder polyp; the present invention also relates to multiple gastrointestinal polyps occurring in both the stomach and small and/or large intestine (including colorectal, anal), such polyps also being referred to herein as gastrointestinal polyps.
Particularly advantageously, the provided astilbin of the invention can be used clinically in the form of a pharmaceutical composition.
The invention provides an application of a pharmaceutical composition containing astilbin in preventing and treating polyps of human or mammals.
The astilbin-containing pharmaceutical composition can comprise a first active agent astilbin and a second active agent. The second active agent comprises one or more of glucocorticoid, immunosuppressant, antibiotic, acid inhibitor and compound obtained from other traditional Chinese medicines, natural medicines or plants. The glucocorticoid provided by the invention comprises prednisone, prednisolone, budesonide, prednisone, hydrocortisone, dexamethasone, betamethasone and the like. The immunosuppressant comprises 6-mercaptopurine, leflunomide, azathioprine, methotrexate, cyclosporine, mycophenolate mofetil, tofacitinib, olatinib, barretinib, TD-1473, rapamycin, everolimus, tacrolimus and the like. The antibiotics comprise clinically common beta-lactams, aminoglycosides, macrolides, lincomycins, polypeptides, quinolones, sulfonamides, antituberculosis drugs, antifungal drugs and other antibiotics. The acid-inhibiting medicine comprises proton pump inhibitors such as omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole and the like, and H2 receptor antagonists such as cimetidine, ranitidine, famotidine, nizatidine, roxatidine and the like. The compounds obtained from other traditional Chinese medicines, natural medicines or plants comprise chlorogenic acid, loganin, phillyrin, forsythoside A, forsythiaside, lobetyolin and the like.
The astilbin-containing pharmaceutical composition can also be a traditional Chinese medicine extract containing astilbin, or a combination of the traditional Chinese medicine extract containing astilbin and one or more of glucocorticoid, immunosuppressant, antibiotic, acid inhibitor and compounds obtained from other traditional Chinese medicines, natural medicines or plants. The traditional Chinese medicine extract is a composition which is obtained from traditional Chinese medicines, natural medicines or plants by adopting a conventional extraction method and takes astilbin as a main active ingredient or index ingredient. The conventional extraction method includes, but is not limited to, water decoction, maceration, percolation, modified gelatin, reflux, solvent extraction, steam distillation, sublimation, supercritical fluid extraction, membrane separation, micronization, flocculation separation of Chinese medicinal materials, semi-bionic extraction, ultrasonic extraction, cyclone extraction, pressurized countercurrent extraction, enzyme method, macroporous resin adsorption, ultrafiltration, and molecular distillation.
Another object of the present invention is to provide a pharmaceutical formulation form of a pharmaceutical composition comprising astilbin, characterized in that the pharmaceutical formulation form is a gastrointestinal administration formulation. The gastrointestinal tract administration preparation is an oral solid preparation, an oral liquid preparation or an enema administration preparation, and preferably the oral solid preparation comprises but is not limited to tablets, capsules, powder, dripping pills, micro-pills, granules and the like. The tablet comprises tablet, coated tablet, and delayed release tablet, and the capsule comprises hard capsule, soft capsule, microcapsule, delayed release capsule, etc. Most preferably tablet, capsule, microcapsule, soft capsule, pellet, and dripping pill. The medicinal auxiliary materials can be one or more selected from a filler or a diluent, a bonding agent, a disintegrating agent, a wetting agent and a lubricating agent, and particularly, the medicinal auxiliary materials can be added with a coloring agent, a sweetening agent and the like according to clinical requirements.
Adding pharmaceutically acceptable adjuvants and health food acceptable adjuvants according to preparation requirement, wherein the adjuvants comprise lubricant, dispersant, binder, diluent, correctant, etc.; the lubricant comprises stearic acid, magnesium stearate, calcium stearate, liquid paraffin, glyceryl monostearate, glyceryl monopalmitate, boric acid, sodium benzoate, sodium acetate, sodium chloride, polyoxyethylene monostearate, polyoxyethylene lauryl ether, DL-leucine, sodium lauryl sulfate, magnesium lauryl sulfate, polyethylene glycol 4000 or 6000, polyoxyethylene monostearate, polyoxyethylene lauryl ether and the like; the dispersing agent comprises white beeswax, sorbitan sesquioleate, poloxamer, sorbitan monostearate, egg yolk lecithin, span 85, span 60, sucrose stearate, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose, aluminum oxide and the like; the binder comprises polyacrylic acid resin I, IV, polyvidone K30, polyvidone K90, hypromellose (60RT50, E50, K100, 100cps), acacia, alginic acid, methylcellulose, carob bean gum, carbomer, chitosan, hydrogenated vegetable oil, liquid glucose, inulin, sunflower oil, hydroxyethyl methylcellulose, etc. The diluent comprises mannitol, maltodextrin, xylitol, lactose, microcrystalline cellulose, zinc oxide, calcium phosphate, calcium hydrogen phosphate, maltitol, maltose, sucrose powder, lactitol, cyclodextrin, sunflower oil, alpha-lactose, dextran, corn starch, ammonium alginate and the like; the correctant comprises Mentholum, diethyl malonate, ethyl propionate, simple syrup, sodium glutamate, methyl salicylate, anhydrous citric acid, sucrose, sodium citrate, trehalose, etc.
The oral pharmaceutical formulations of the present invention may be prepared using conventional techniques and equipment in the pharmaceutical arts.
It is still another object of the present invention to provide astilbin and pharmaceutical compositions comprising astilbin in a clinically effective amount for treating polyps, human effective dose is 0.01mg/kg to 120mg/kg, preferably 1mg/kg to 20mg/kg, 20mg/kg to 80mg/kg, 80mg/kg to 120mg/kg, most preferably 20mg/kg to 80 mg/kg.
The astilbin provided by the invention is a compound with a chemical name of (2R, 3R)5, 7, 3 ', 4' -tetrahydroxyflavanonol-3-O-alpha-L-rhamnopyranoside. In the main source of astilbin, the glabrous greenbrier rhizome is the dried rhizome of Smilax glabra Roxb. The Engelhardtia roxburghiana Wall of Juglandaceae family has high content of astilbin. The grape is Vitis vinifera L.of Vitaceae, and astilbin exists in the berry (skin, juice, seed) part.
The advantages of the invention are as follows:
the composition can be used for treating and preventing polyp, including blocking or delaying postoperative recurrence of polyp.
The astilbin composition has strong pharmacological action, obvious effect of treating intestinal polyps, good safety, long-term taking and good medicinal prospect.
Astilbin has rich sources, simple preparation process, easy preparation into various dosage forms and easy popularization.
Drawings
FIG. 1 shows the effect of astilbin on the number and size of colorectal polyps in mice. Statistical plots of intestinal polyp number and size in mice (Mean ± SD, n ═ 6, × P <0.05, × P < 0.01, × P < 0.001).
FIG. 2 is a graph showing the effect of astilbin on thymus index and spleen index in mice. Effect of test drug on thymus index and spleen index in mice (Mean ± SD, n ═ 6).
FIG. 3 is a graph showing the effect of astilbin on the number and size of intestinal polyps in APCmin/+ mice. Statistical plots of number and size of intestinal polyps in APCmin/+ mice (Mean ± SD, n ═ 6, × P <0.05, × P < 0.01, × P < 0.001).
FIG. 4 is a graph showing the effect of astilbin in combination with loganin on the number and size of colorectal polyps in mice. Statistical plots of number and size of intestinal polyps in mice (Mean ± SD, n ═ 6, × P <0.05, × P < 0.01, × P < 0.001).
Detailed Description
The present invention will be described in further detail below by way of examples, but it should not be construed that the scope of the above-described subject matter of the present invention is limited to the following examples. Modifications and variations that may be made in accordance with the teachings of the present invention without departing from the foregoing teachings and practice are intended to be included within the scope of the present invention.
Example 1 preparation of granules containing astilbin extract
Rhizoma Smilacis Glabrae decoction pieces are purchased from Beijing Wan Chinese medicinal tablet factories in Bozhou city, are added with 10 times of water and soaked for 2h at normal temperature, and are heated and refluxed for extraction for 2h, and water extract is collected. Extracting the residue with water for 2 hr, mixing the two extractive solutions, filtering, and concentrating to obtain extract containing 3g crude drug per ml, wherein the astilbin content in the extract is 8.12%. Mixing the extract with appropriate amount of adjuvants, sieving with 20 mesh nylon sieve, granulating, oven drying, and grading.
EXAMPLE 2 preparation of astilbin tablets
Weighing 30g of astilbin, 20g of powdered sugar, 40g of lactose and 45g of sodium carboxymethyl starch, fully mixing the materials, sieving with a 100-mesh sieve, adding 5% PVP-K30 aqueous solution to prepare a soft material, and granulating with a 20-mesh nylon sieve. After drying, the granules were compressed with magnesium stearate using an external lubricating device to give tablets weighing about 150mg and about 1000 tablets.
Example 3 preparation of astilbin capsules
Mixing astilbin with 10% starch slurry, making into soft material, sieving with 20 mesh nylon sieve, and granulating. Drying the granules, finishing granules, and filling the granules into capsules to obtain the astilbin capsules.
Example 4 establishment of mouse model of AOM in combination with DSS-induced intestinal polyps and evaluation of Astilbin potency
1 test materials
1.1 animals
BALB/c mice, SPF grade, weight 18-22g, male, Beijing Wintorlington laboratory animal technology Limited, license number: SCXK (threo) 2016-. The mice are raised in cages in the animal experiment center of Nanjing Chinese medicine university, and the raising license is as follows: SYXK2018-0049 is moderate in illumination, and has the room temperature of 22-25 ℃ and the humidity of 50-60%.
1.2 drugs and reagents
Test agent configuration:
dissolving astilbin in Tween 80, diluting with normal saline to desired concentration, and making into suspension, and mixing before administration. The administration volume was 0.1mL/10g, and the administration dose was 25mg/kg and 50 mg/kg. Molding reagent: AOM (azoxymethane), sigma, batch number: SLCC 0424. DSS (dextran sulfate sodium salt), MP biomedicals, lot number: q1723.
2 Experimental methods
2.1 animal grouping, modeling and administration
Grouping: after the mice are bred adaptively, the mice are divided into a blank group, a model group, a test drug low-dose group and a test drug high-dose group randomly according to weight stratification.
Establishing an AOM combined DSS three-cycle model: except for the blank group, mice in each group were given 10mg/kg of AOM intraperitoneally on day 1 of week 1 and simultaneously given 2.5% DSS drinking water continuously for 1 week, and were free to drink in plain drinking water for 2 weeks, for a total of 3 weeks as one cycle. In the same way as the first cycle, AOM was intraperitoneally injected at a dose of 10mg/kg on day 1 at weeks 4 and 7, and given 2 weeks of 2.5% DSS drinking, respectively, and ordinary drinking water for the remaining time, for 9 weeks for 3 cycles. The mice in the blank group are injected with normal saline in the abdominal cavity on the same day of the injection of the abdominal cavity of the model group, and common drinking water is given from the beginning to the end of the experiment for drinking.
Administration: starting from day 1 of week 1, the mice in the administration group are subjected to intragastric administration of the test drug 1 time per day, the intragastric administration is continued for 9 weeks during the molding period, and the intragastric administration is continued for 1 week after the molding is completed, and the administration is continued for 10 weeks in total.
2.2 index detection:
closely observing and recording the weight, diet, defecation and other conditions of the mouse during the molding period, and taking the thymus and the spleen on the last day of the 10 th week to calculate the thymus index and the spleen index; the method comprises the steps of obtaining the whole colorectal of a mouse from the tail end of a cecum to an anus, longitudinally splitting along an intestinal canal, cleaning intestinal excrement by using normal saline, placing the mouse on a dissecting table with an intestinal mucosa facing upwards, observing whether an intestinal mucosa tissue has an inflammatory reaction and polyp generation, and recording the number, the position, the size and the like of the polyp generation.
2.3 statistical methods:
data results are expressed as mean ± standard deviation (mean ± SD), and comparisons of differences between groups were statistically significant with P <0.05 using the one-way ANOVA analysis method of GraphPad Prism 7 software and comparisons between groups using Dunnett's test.
3, experimental results:
through AOM combined DSS modeling, a certain number of polyps are obviously formed in the large intestine of the model mouse, and the tested drugs can obviously inhibit the generation of the polyps, obviously reduce the number of the polyps and reduce the volume of the polyps. The inhibition rates of the low-dose and high-dose test drugs are 44.78% and 52.24%, respectively. Meanwhile, the tested drug has no obvious influence on thymus index and spleen index of mice (table 1 and figures 1 and 2).
Table 1: influence of test drugs on the number of polyps in the large intestine of mice
### P<0.001 compared to blank; ** P<0.01, *** P<0.001 compared to the model group.
Example 5APC min/+ Evaluation of drug efficacy of test substance by spontaneous polyp mouse model
1 materials of the experiment
1.1 animals
Line name B6/JGpt-Apc em1Cin(MinC) mice/Gpt, SPF grade, 6 weeks old, male. Wild type C57/B6J mice, SPF grade, 6 weeks old, males. Purchased from Jiangsu Jiejiaokang Biotech, Inc., license number: SCXK (su) 2018-. The mice are raised in cages in the animal experiment center of Nanjing Chinese medicine university, and the raising license is as follows: SYXK2018-0049, which is moderate in illumination, has the room temperature of 22-25 ℃ and the humidity of 50-60%.
1.2 test agent configuration:
completely grinding astilbin with Tween 80, mixing, diluting with normal saline to desired concentration, and making into suspension, and mixing before each administration. The administration volume was 0.1mL/10g, and the administration dose was 25mg/kg and 50 mg/kg.
2 method of experiment
2.1 animal grouping and dosing:
APC min/+ after the mice are adaptively raised for 1 week, the mice are randomly divided into a model group, an astilbin low dose group (25 mg/kg) and an astilbin high dose according to weight stratificationAmount group (50 mg/kg). The mice in the administration group are gavaged with corresponding dose of astilbin, 1 time per day, and administered for 10 weeks in total, and wild type control mice and APC min/+ The model group mice were gavaged with an equal volume of saline. During which time groups of mice had free access to feed.
2.2 index detection:
closely observing and recording the weight, diet, defecation and other conditions of the mouse during administration, taking the whole section of the intestine of the mouse 24 hours after the last administration, longitudinally splitting the intestine along the intestinal canal, cleaning the intestinal contents by physiological saline, placing the intestine on an anatomical table with the intestinal mucosa facing upwards, observing whether the intestinal mucosa tissue has inflammatory reaction and polyp, and recording the number and the size of the polyp.
2.3 statistical methods:
data results are expressed as mean ± standard deviation (mean ± SD), and comparisons of differences between groups were statistically significant with P <0.05 using the one-way ANOVA analysis method of GraphPad Prism 7 software and comparisons between groups using Dunnett's test.
3, experimental results:
APC min/+ a certain number of polyps are obviously formed in the intestinal part of a mouse, and the number of the polyps can be obviously reduced and the volume of the polyps can be reduced by giving the test drug astilbin. The inhibition rates of the low and high dose test drugs were 27.19% and 44.74%, respectively (table 2, fig. 3).
Table 2: test drug vs APC min/+ Effect of the number of intestinal polyps in mice
### P<0.001 compared to wild type control group; * P<0.05, *** P<0.001 compared to the model group.
Example 6 evaluation of the Effect of astilbin in combination with loganin on intestinal polyp formation in mice
1 materials of the experiment
1.1 animals
BALB/c mice, SPF grade, weight 18-22g, male, Beijing Wintorlington laboratory animal technology Limited, license number: SCXK (threo) 2016-. The mice are raised in cages in the animal experiment center of Nanjing Chinese medicine university, and the raising license is as follows: SYXK2018-0049 is moderate in illumination, and has the room temperature of 22-25 ℃ and the humidity of 50-60%.
1.2 drugs and reagents
Test agent configuration:
completely dissolving astilbin and loganin in Tween 80, respectively, diluting with normal saline to desired concentration, and making into suspension, and mixing well before each administration. The administration volume is 0.1mL/10g, and the administration dose is 50 mg/kg.
Molding reagent: AOM (azoxymethane), sigma, batch number: SLCC 0424. DSS (dextran sulfate sodium salt), MP biomedicals, lot No.: q1723.
2 Experimental methods
2.1 animal grouping, modeling and administration
Grouping: after the mice are adaptively fed, the mice are randomly divided into a blank group, a model group, an astilbin 50mg/kg group and a loganin 50mg/kg group according to weight layering.
Establishing an AOM combined DSS three-cycle model: except for the blank group, mice in each group were given 10mg/kg of AOM intraperitoneally on day 1 of week 1 and simultaneously given 2.5% DSS drinking water continuously for 1 week, and were free to drink in plain drinking water for 2 weeks, for a total of 3 weeks as one cycle. As with the first cycle, AOM was intraperitoneally administered at a dose of 10mg/kg on day 1 at weeks 4 and 7, and 2.5% DSS was administered for 2 weeks, respectively, and plain drinking water was administered for the remaining time, for 9 weeks and 3 cycles. The mice in the blank group are injected with normal saline in the abdominal cavity on the same day of the injection of the abdominal cavity of the model group, and common drinking water is given from the beginning to the end of the experiment for drinking. Starting from day 1 of week 1, the mice in the administration group are subjected to intragastric administration of the test drug 1 time per day, the intragastric administration is continued for 9 weeks during the molding period, and the intragastric administration is continued for 1 week after the molding is completed, and the administration is continued for 10 weeks in total.
2.2 index detection:
closely observing and recording the weight, diet, defecation and other conditions of the mouse during the molding process, obtaining the whole colorectal from the tail end of the cecum to the anus on the last day of the 10 th week, longitudinally splitting along an intestinal canal, cleaning intestinal excrement by using normal saline, upwards placing the intestinal mucosa on an anatomical table, observing whether an intestinal mucosa tissue has an inflammatory reaction or polyp, and recording the number and the size of the polyp.
2.3 statistical methods:
data results are expressed as mean ± standard deviation (mean ± SD), and comparisons of differences between groups were statistically significant with P <0.05 using the one-way ANOVA analysis method of GraphPad Prism 7 software and comparisons between groups using Dunnett's test.
3 results of the experiment
Through AOM combined with DSS modeling, a certain amount of polyps are obviously formed in the large intestine of the mice in the model group, and the generation of the polyps can be obviously inhibited by the administration of astilbin or the combined administration of astilbin and loganin, the number of the polyps is obviously reduced, and the volume of the polyps is reduced. Astilbin has a polyp suppression rate of 54.84%, and astilbin and loganin used in combination have a polyp suppression rate of 64.52% (table 3 and fig. 4).
Table 3: influence of test drugs on the number of colorectal adenomas of mice
### P<0.001, compared to blank; * P<0.05, ** P<0.01 compared to the model set.
Claims (13)
1. Use of astilbin in preparing medicine for preventing and/or treating polyp of human or mammal is provided.
2. Use according to claim 1, characterized in that said polyps comprise human or mammalian digestive tract polyps, endometrial polyps, cervical polyps, laryngeal polyps, nasal polyps.
3. Use according to claim 2, characterized in that the polyp of the digestive tract is gastrointestinal polyposis syndrome.
4. Use according to claim 3, characterized in that the gastrointestinal polyposis syndrome is Cronkhite-Canada syndrome.
5. Use according to claim 2, characterized in that the polyp of the digestive tract is a polyp of the gastrointestinal tract or a polyp of the gallbladder.
6. An application of a pharmaceutical composition containing astilbin in preparing medicines for preventing and/or treating human or mammal polyp is characterized in that the pharmaceutical composition is tablets, dispersible tablets, capsules, soft capsules, microcapsules, granules, injections, powder injections, freeze-dried powder injections, micro-pills, dropping pills, syrups, powders, extracts, soft extracts and oral liquid preparations.
7. Use according to claim 6, characterized in that said polyps comprise human or mammalian digestive tract polyps, endometrial polyps, cervical polyps, laryngeal polyps, nasal polyps.
8. Use according to claim 7, characterized in that the polyp of the digestive tract is gastrointestinal polyposis syndrome.
9. Use according to claim 8, characterized in that the gastrointestinal polyposis syndrome is Cronkhite-Canada syndrome.
10. Use according to claim 6, characterized in that the polyp of the digestive tract is a polyp of the gastrointestinal tract or a polyp of the gallbladder.
11. Use according to any one of claims 6 to 10, characterized in that the pharmaceutical composition is a formulation for gastrointestinal administration.
12. Use according to any one of claims 6 to 10, characterized in that the pharmaceutical composition is an oral solid formulation.
13. Use according to any one of claims 6 to 10, characterized in that the pharmaceutical composition is an oral liquid formulation.
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CN108853404A (en) * | 2018-07-24 | 2018-11-23 | 近晟(上海)医药科技有限公司 | A kind of compound Chinese medicinal preparation and preparation method thereof for treating skin and mucous membrane disease |
CN112274607A (en) * | 2019-07-25 | 2021-01-29 | 南京三同医药科技有限公司 | Pharmaceutical composition for treating polyp |
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