CN112843123A - Application of Fujian cyclobalanopsis glauca extract in preparation of medicine for treating stomach related diseases - Google Patents
Application of Fujian cyclobalanopsis glauca extract in preparation of medicine for treating stomach related diseases Download PDFInfo
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- CN112843123A CN112843123A CN201911100214.5A CN201911100214A CN112843123A CN 112843123 A CN112843123 A CN 112843123A CN 201911100214 A CN201911100214 A CN 201911100214A CN 112843123 A CN112843123 A CN 112843123A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/49—Fagaceae (Beech family), e.g. oak or chestnut
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- 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
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- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
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Abstract
The invention discloses a method for preparing an extract of cyclobalanopsis glauca H+‑K+-an ATPase inhibitor and its use in the manufacture of a medicament for the prevention or treatment of a gastric related disorder. And a preparation method of the extract of the Fujian cyclobalanopsis glauca. The stomach related diseases comprise gastric mucosal hemorrhage, gastric ulcer and reflux esophagitis. The gastric mucosal hemorrhage comprises gastric mucosal hemorrhage caused by indomethacin and gastric mucosal hemorrhage caused by cold stress.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a new application of extracted cyclobalanopsis glauca, namely an application of an extract of cyclobalanopsis glauca in preparing a medicine for preventing or treating stomach-related diseases and an application of the extract in preparing an H + -K + -ATP enzyme inhibitor.
Background
Cyclobalanopsis chungii (Metc.) Y.C.Hsu et H.W.) Is FagaceaeCyclobalanopsis plants, more than 150 species of which are mainly distributed in tropical and subtropical regions of asia. 77 and 3 varieties exist in China, Fujian Qinggang is mainly produced in Jiangxi, Fujian, Hunan, Guangdong, Guangxi and other places, grows in shady slopes and valleys with the elevation of 200-plus-one 800 meters, is a warm-land, neutral and shady tree species and is mainly used as an elegant garden ornamental tree species. No medical record is found.
We found that the extract of Cyclobalanopsis glauca has high gastric H in a large amount of screening work+-K+The activity of the ATP enzyme inhibition effect, the extract has obvious protection effect on gastric mucosa bleeding caused by indomethacin and cold stress, the extract has the effect of promoting ulcer healing on a chronic acetic acid ulcer model, and no report of research on treatment of stomach illness by Fujian Qinggang is seen so far.
Disclosure of Invention
The invention aims to provide the application of the cyclobalanopsis glauca extract in preparing the medicines for preventing or treating the stomach-related diseases.
In order to solve the technical problem, the invention provides the following technical scheme:
the first aspect of the technical scheme of the invention provides the preparation H of the extract of the Fujian cyclobalanopsis glauca+-K+-use in an ATPase inhibitor.
The invention also provides application of the extract of the Fujian cyclobalanopsis glauca in preparing the medicine for preventing or treating stomach related diseases.
Further, the stomach related diseases comprise gastric mucosal hemorrhage and gastric ulcer.
Furthermore, the bleeding of the gastric mucosa comprises the bleeding of the gastric mucosa caused by indomethacin and the bleeding of the gastric mucosa caused by cold stress.
Further, the preparation method of the fagopyrum tataricum extract is characterized by comprising the following steps: the solvent for extracting cyclobalanopsis glauca is water, alcohol, or mixture of water and alcohol, and is heated under reflux for 3 times. Preferred alcohols include methanol, ethanol, isopropanol, butanol, and the like. After the above steps are finished, the filtrates are combined, and the dregs of a decoction are filtered out. The filtrates were combined and further concentrated under reduced pressure to a paste.
Further, the preparation method of the fagopyrum tataricum extract is characterized by comprising the following steps: extracting raw materials with water at room temperature or under heating (or refluxing) in static or dynamic state, wherein the extraction solvent amount is 4-14 times of the weight of raw materials, the extraction can be continuously or intermittently performed, the intermittent extraction can be repeated for 1-4 times, filtering to remove residue, heating and concentrating the filtrate under normal pressure or reduced pressure in dynamic state to volume of 1-5 times of the weight of raw materials, cooling, filtering to remove insoluble substances, mixing the filtrates, and concentrating to obtain paste; or extracting the raw materials with alcohols (methanol, ethanol, isopropanol, butanol, etc.) or water-containing alcohol (40-90%) at room temperature or under heating (or refluxing) statically or dynamically, wherein the extraction solvent amount is 4-14 times of the weight of the raw materials, the extraction can be continuously or intermittently carried out, the intermittent extraction can be repeated for 1-4 times, filtering to remove residue, heating and concentrating the filtrate under normal pressure or reduced pressure in a dynamic state to a volume 1-5 times of the weight of the raw materials, cooling, centrifuging to remove insoluble substances, washing the insoluble substances with a small amount of water for 1-3 times, mixing the filtrates, and concentrating into paste.
The extract can be freeze-dried or vacuum-dried into dry powder, or the concentrated liquid can be directly spray-dried into dry powder for preparation molding.
In a second aspect of the present invention, there is provided a pharmaceutical composition for use in the preparation of H+-K+-use of an atpase inhibitor, characterized in that said pharmaceutical composition comprises an extract of cyclobalanopsis glauca according to the first aspect of the present invention, together with a pharmaceutically acceptable carrier or excipient.
The second aspect of the present invention also provides a use of a pharmaceutical composition for preparing a medicament for preventing or treating stomach-related diseases, wherein the pharmaceutical composition comprises the extract of fava key according to any one of claims 1 to 7 and a pharmaceutically acceptable carrier or excipient.
The beneficial technical effects are as follows: the application of the extract of the Fujian cyclobalanopsis glauca in preparing the medicine for treating the gastric ulcer is found for the first time and is not reported at home.
Detailed Description
The raw medicinal materials are identified as the Fujian cyclobalanopsis glauca by the institute of medicine of Chinese academy of medical sciences specimen room.
Example 1 preparation of Fujian cyclobalanopsis glauca extract (aqueous extract)
1 kg of Fujian cyclobalanopsis glauca branches and leaves are extracted by distilled water under reflux for three times, one hour each time, and the extract is concentrated under reduced pressure to obtain 47g of water extract.
Example 2 preparation of Fujian cyclobalanopsis glauca extract (alcohol extract example)
3.4 kg of Fujian cyclobalanopsis glauca, adding 90% ethanol in an amount which is 6 times that of the Fujian cyclobalanopsis glauca, soaking overnight or 4 hours, slowly heating to boil, refluxing for 1 hour, and filtering; repeating the whole process twice, combining filtrates, concentrating under reduced pressure at 60-70 deg.C under 85-98KPa, adding water of the same weight as the medicinal materials when concentrating to completely remove ethanol, heating to boil, cooling, centrifuging to remove insoluble substances, adding a small amount of water to wash the insoluble substances for three times, combining filtrates, concentrating under reduced pressure at 60-70℃, drying under reduced pressure (at 70-80 deg.C under 85-98 KPa), and drying under reduced pressure (at 70-80 deg.C under 85-98 KPa) to obtain 167g extract.
Pharmacological experiments:
the samples used in the pharmacological experiments were all the samples obtained in the preparation of the extract of cyclobalanopsis glauca (example of alcoholic extract) of example 2.
Experimental example 1. Fujian cyclobalanopsis glauca extract vs. H+-K+Influence of ATPase Activity
The method comprises the following steps: taking a 96-well plate, adding lysozyme and 1.0mg/ml and 0.2mg/ml of the extract of the green fagopyrum futoki in blank and control, and 20ul of rabeprazole sodium 10-3mol/L and 10-4 mol/L. Adding pig H diluted by 20 times with the reaction solution+-K+160ul of ATPase, incubated at 37 ℃ for 20 minutes, 20ul of 20mg/ml ATP was added, and no ATP was added to the blank. The reaction was carried out at 37 ℃ for 30 minutes. The reaction was stopped by adding 10% TCA 50 ul. Blank plus 20mg/ml ATP 20 ul. 50 mul of the enzyme-linked immunosorbent assay solution is placed in a 96-hole enzyme label plate, 200ul of the phosphorus solution is added for color reaction, and color comparison is carried out at 660 nm. The inhibition was calculated as (control-sample)/(control-blank) × 100%.
As a result: extract of Fujian cyclobalanopsis glauca on pig stomach H+-K+The ATPase activity has stronger inhibition effect, and the inhibition rates of 100ug/ml and 20ug/ml are respectively 59% and 9%. Rabeprazole sodium 10-4mol/L and 10-5mol/The inhibition rates for L were 71% and 57%, respectively.
Experimental example 2 Effect of Fujian cyclobalanopsis glauca extract on rat anti-inflammatory pain type gastric ulcer model
The method comprises taking male wistar rat, and fasting for 48 hours. The test pieces were randomly divided into a control group, a rabeprazole sodium group and an extract group of faggot, and each group had 5 pieces. The administration is 10 ml/kg. The control group was administered with vehicle, rabeprazole sodium by gavage at 10mg/kg, and the extract of cyclobalanopsis glauca at 500 mg/kg. The abdominal cavity is injected with indomethacin 35mg/kg after 0.5 hour, the cervical vertebra is removed after 6.0 hours, the rat is killed, the stomach is taken out, 10ml of water is injected, the rat is fixed in 3% formaldehyde solution, and the bleeding point of the mucous membrane part is counted. Significance testing was performed using the t-program.
As a result, after the extract of the cyclobalanopsis glauca is administrated by gastric lavage in advance, the bleeding point of the gastric mucosa caused by indomethacin can be obviously reduced, and the extract of the cyclobalanopsis glauca has obvious protective effect on the bleeding of the gastric mucosa caused by indomethacin. Compared with the control, the inhibitor has significant difference, and the inhibition rate is 46%. Rabeprazole sodium inhibits 18% at the used dose.
Experimental example 3 Effect of Fujian cyclobalanopsis glauca extract on Water restraint ulcer model in rats
The method comprises the following steps: male wistar rats were taken and fasted for 48 hours. The test pieces were randomly divided into a control group, a rabeprazole sodium group and an extract group of faggot, and each group had 5 pieces. The administration is 10 ml/kg. The control group was administered with vehicle, 20mg/kg of rabeprazole sodium, and 500mg/kg of the extract of cyclobalanopsis glauca. After 0.5 hour, the rats were placed in a special stress cage and placed in a water bath at 16 ℃ until the water surface reached the xiphoid process of the rats. Animals were sacrificed after 6 hours. Taking out the stomach, injecting 10ml of water, fixing in 3% formaldehyde solution, shearing to stimulate the appetite, and counting the number of ulcer at the mucous membrane part.
As a result: after the extract of the cyclobalanopsis glauca is perfused into the stomach in advance and administered, the bleeding point of the gastric mucosa caused by cold stress can be obviously reduced, and the extract of the cyclobalanopsis glauca has better protective effect on the bleeding of the gastric mucosa caused by cold stress. Compared with the control, the inhibitor has significant difference, and the inhibition rate is 44%. Rabeprazole sodium has an inhibition rate of 97% under the used dosage.
Experimental example 4 Effect of extract of Cyclobalanopsis glauca on model of chronic acetic acid ulcer in rat
The method comprises the following steps: rats were fasted for 24 hours, anesthetized with 0.5mg/kg sodium pentobarbital, the abdominal cavity was opened, the stomach was gently flattened, and 20 μ l of 30% acetic acid was injected transpylorically into the glandular stomach and the abdominal cavity was closed. Animals were randomly grouped, as per table 1. The administration is started the next day after the operation, the dosage of the extract of the fagopyrum foenum-graecum is 500mg/kg, the dosage of the rabeprazole sodium is 100mg/kg, and the vehicle is administered in a contrast mode. Once daily for 10 consecutive days. The rats were fasted for 24 hours after the last dose, the animals were sacrificed the next day, the stomach was removed and injected with 10ml of water and fixed in 3% formalin. After 30 minutes, the stomach was cut along the greater curvature of the stomach, laid flat on a glass plate, photographed with a digital camera, and the images were processed with spot advanced software to determine the area of the ulcer.
Table 1: effect of the extract of Cyclobalanopsis glauca on Chronic acetic acid ulcer model
As a result: the ulcer area of 500mg/kg of the extract of cyclobalanopsis glauca in rats was reduced by 19.1%. The ulcer area of the rabeprazole sodium is reduced by 33.0 percent when the rabeprazole sodium is 100 mg/kg. The result shows that the extract of the Fujian cyclobalanopsis glauca has the function of promoting ulcer healing on a chronic acetic acid ulcer model.
Preparation of the formulations
The extract or extract powder prepared in the embodiments 1 and 2 is added with relevant auxiliary materials to be prepared into medicinal granules, powder, capsules, tablets, oral liquid and other dosage forms.
1. Instant granule
Comprises soluble granule and block agent, and is prepared by mixing the dry powder obtained by the first and second methods with appropriate amount of excipient (selected from dextrin, starch, microcrystalline cellulose, alginic acid, sodium alginate, carboxymethyl starch, low-substituted hydroxypropyl cellulose, etc.), press drying to obtain granule, grading, and packaging in moisture-proof packaging material (such as thick plastic, aluminum foil, etc.). Or adding the above excipient into the extract, granulating by wet method, drying, and making into block.
2. Capsule preparation
Adding appropriate amount of adjuvants (such as calcium carbonate, mannitol, magnesium carbonate, magnesium oxide, and silica gel micropowder), lubricant (such as pulvis Talci, magnesium stearate, glycol ester, and silicone), binder (such as mineral oil and edible oil), mixing to obtain dry powder or granulating, and making into capsule. Or making into soft material with proper amount of excipient (polyethylene glycol, oil, etc.) by pumping method, and packaging in sealed aluminum-plastic package.
3. Tablet formulation
Including ordinary tablets, film-coated tablets, and the like. Adding appropriate amount of diluent (selected from dextrin, starch, microcrystalline cellulose, mannitol, etc.), appropriate amount of binder (selected from water, ethanol, starch slurry, cellulose, etc.), appropriate amount of disintegrating agent (selected from starch, alginic acid, sodium alginate, carboxymethyl starch, low-substituted hydroxypropyl cellulose, etc.), and appropriate amount of lubricant (selected from pulvis Talci, magnesium stearate, polyethylene glycol, etc.) into the dry powder or extract obtained by the first and second methods, granulating by conventional wet method, drying, and tabletting. The film-coated tablet can be prepared by coating with film-forming material (such as cellulose and polyvinyl alcohol) and packaging into sealed bottle or aluminum-plastic plate.
4. Oral liquid
The preparation method comprises dissolving the dry powder or extract obtained by the first and second methods in water or ethanol, adding appropriate amount of stabilizer (selected from disodium ethylene diamine tetraacetate, sodium pyrosulfite, sodium thiosulfate, VC derivatives, etc.) or appropriate amount of antiseptic (selected from benzoic acid, p-hydroxybenzoate esters, sorbic acid, etc.), and packaging in sealed bottles.
5. Powder preparation
Appropriate amount of sweetener such as D-xylose, xylitol, maltitol, steviosin, and radix asparagi Matricariae Fellissilifoliae can be added into the above dosage forms.
Claims (10)
1. Preparation H of Fujian cyclobalanopsis glauca extract+-K+-use in an ATPase inhibitor.
2. Application of Fujian cyclobalanopsis glauca extract in preparing medicine for preventing or treating stomach related diseases.
3. The use according to claim 2, wherein said stomach related disorders comprise bleeding of the gastric mucosa, gastric ulcers, reflux esophagitis.
4. The use according to claim 3, wherein said bleeding from the gastric mucosa comprises bleeding from the gastric mucosa caused by indomethacin, bleeding from the gastric mucosa caused by cold stress.
5. The use as claimed in any one of claims 1 to 4, wherein the extract of Cyclobalanopsis glauca is prepared by: reflux-extracting rhizoma Begoniae Evansianae with solvent under heating for 3 times, mixing filtrates, filtering to remove residue, and concentrating the filtrate under reduced pressure to obtain paste.
6. The use according to claim 5, wherein the solvent is selected from the group consisting of water, alcohols, and mixtures of water and alcohols in varying proportions.
7. Use according to claim 6, characterized in that the alcohol is methanol, ethanol, isopropanol, butanol or a mixture thereof.
8. Preparation of a pharmaceutical composition in H+-K+-use of an atpase inhibitor, characterized in that said pharmaceutical composition comprises the extract of fava-glauca of any of claims 1 to 7, together with a pharmaceutically acceptable carrier or excipient.
9. Use of a pharmaceutical composition for preparing a medicament for preventing or treating stomach-related diseases, wherein the pharmaceutical composition comprises the extract of fava-glauca of any one of claims 1 to 7 and a pharmaceutically acceptable carrier or excipient.
10. The use according to claim 9, wherein said stomach related disorders comprise bleeding of the gastric mucosa, gastric ulcers, reflux esophagitis.
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| CN201911100214.5A CN112843123B (en) | 2019-11-12 | 2019-11-12 | Application of Fujian cyclobalanopsis glauca extract in preparation of medicine for treating stomach related diseases |
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| CN201911100214.5A CN112843123B (en) | 2019-11-12 | 2019-11-12 | Application of Fujian cyclobalanopsis glauca extract in preparation of medicine for treating stomach related diseases |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101018557A (en) * | 2004-09-13 | 2007-08-15 | 辻田隆广 | Carbohydrase inhibitors derived from chestnut and use thereof |
| CN101297880A (en) * | 2007-04-30 | 2008-11-05 | 常州高新技术产业开发区三维工业技术研究所有限公司 | Active extract containing phlorizin and uses thereof |
| CN101874824A (en) * | 2009-05-01 | 2010-11-03 | 常州高新技术产业开发区三维工业技术研究所有限公司 | Active extract containing trilobatin and application thereof |
| WO2015114855A1 (en) * | 2014-01-28 | 2015-08-06 | 一丸ファルコス株式会社 | Kinesin inhibitor containing luteolin or glucoside thereof as active ingredient |
-
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- 2019-11-12 CN CN201911100214.5A patent/CN112843123B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101018557A (en) * | 2004-09-13 | 2007-08-15 | 辻田隆广 | Carbohydrase inhibitors derived from chestnut and use thereof |
| CN101297880A (en) * | 2007-04-30 | 2008-11-05 | 常州高新技术产业开发区三维工业技术研究所有限公司 | Active extract containing phlorizin and uses thereof |
| CN101874824A (en) * | 2009-05-01 | 2010-11-03 | 常州高新技术产业开发区三维工业技术研究所有限公司 | Active extract containing trilobatin and application thereof |
| WO2015114855A1 (en) * | 2014-01-28 | 2015-08-06 | 一丸ファルコス株式会社 | Kinesin inhibitor containing luteolin or glucoside thereof as active ingredient |
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