CN101461831B - Geranium extract - Google Patents
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Abstract
The invention relates to a novel heroubill geranium extract and a preparation method thereof, in particular to a heroubill geranium extract containing corilagin and application of the heroubill geranium extract in medicines for treating or preventing diseases related to gastric acid hypersecretion.
Description
Technical field
The present invention relates to a kind of new Herba Erodii extract and preparation method thereof, relate to Herba Erodii extract that contains corilagin and preparation method thereof particularly, the purposes that also relates to described Herba Erodii extract gastric acid inhibitory secretion, reduction gastric acidity, and the purposes for the treatment of or preventing diseases such as hyperchlorhydria, peptide ulceration, chronic gastritis.
Background technology
Herba Erodii is China's medicinal material commonly used, it is of a great variety, comprise yak seedling section yak seedling platymiscium yak seedling (Erodium stephanianum Willd) and equal Geranium plant Herba Erodii (Geraniumwilfordii Maxim), and nepal cranesbill (Geranium nepalense Sweet.), thick root Herba Erodii (G.dahuricum DC), Pelargonium (G.sibiricum L.), Carolina Cranesbill Herb (G.caroliniznum L.), Herba Geranii eriostemonis (G.eriostemon Fisch.ex.DC), suede back of the body Herba Erodii (Geranium vlassovianum), Qingdao Cranesbill (Geranium tsingtauense Yabe), Robetium macrorrhizum (Geranium macrorrhizum) and geranium thunbergii (G.thunbergii Sieb.et Zucc.) etc.Chemical ingredients in the Herba Erodii is numerous, mainly comprises tannin, flavonoid, organic acid and volatilization wet goods.Along with people to the deepening continuously of Herba Erodii research, its increasing pharmacological action constantly is found, as anti-inflammatory, analgesic activity, anti-microbial effect, antivirus action, antioxygenation, immunization, antitussive effect, anti-diarrhea effect, hepatoprotective effect, antitumor action, blood sugar reducing function, anastalsis etc.Yet yet there are no the active relevant reports in aspect such as the secretion of Herba Erodii gastric acid inhibitory, reduction gastric acidity.The contriver is engaged in the experimental study of Herba Erodii for a long time, finds that Herba Erodii has the gastric acid inhibitory secretion, reduces the activity of gastric acidity, aspect the diseases such as treatment or prevention hyperchlorhydria, peptide ulceration, chronic gastritis good effect is being arranged.
Hyperchlorhydria is meant gastric juice (comprising compositions such as hydrochloric acid and stomach en-) supersecretion, and makes the patient feel to have a stomach upset, sour regurgitation water, heartburn (stomach burning sensation).Slight hyperchlorhydria mainly shows as and occurs stomach burning sensation, sour regurgitation repeatedly, if hyperchlorhydria infringement stomach mucous membrane, also can cause stomachache, feel sick, symptom such as vomiting, hyperchlorhydria also may be further developed into peptide ulceration, even perforated ulcer occurs.
The medicine of hyperchlorhydria can be divided three classes: the first kind be in and the hydrochloric acid in gastric juice medicine, as sodium bicarbonate, aluminium hydroxide etc.; Second class is for pressing down sour medicine, as Cimitidine Type A/AB, Ranitidine HCL, famotidine and proton pump inhibitor etc.; The 3rd class is for increasing the medicine of gastric mucosal defense ability, as bismuth preparation etc.
Peptide ulceration is a kind of global common disease and frequently-occurring disease, estimates that about 10% crowd was once suffering from this disease in life.Peptide ulceration mainly means stomach ulcer and duodenal ulcer, it is a kind of multi-pathogenesis disease, its morbidity is relevant with multiple factor, as hydrochloric acid in gastric juice, stomach en-, Hp (Hp) infection, heredity, physique, environment, diet, living habit, neural mental element etc., by different approaches or mechanism, cause above-mentioned invasion and attack effect to strengthen and or preventing mechanism weaken, all can inspire ulcer and take place.Along with people's deepening continuously to hydrochloric acid in gastric juice generting machanism and gastric mucosal defense function understanding, methods of treatment to peptic ulcer is also being updated, at present main methods of treatment have (referring to: the time space, the treatment of stomach ulcer and gastric acid secretion, the biology circular, 1994,29 (12), 14-15):
Antiacid pharmacotherapy:
At present, generally acknowledge that it is satisfied ulcer healing environment and indispensable treatment condition that stomach inner pH value maintains more than the 3.5-4.0.Therefore gastric acid inhibitory secretion, improving the interior pH of stomach is the basis of treatment of peptic ulcer.Antacid generally is an alkaline drug, as sodium bicarbonate etc., by reducing acidity in the stomach with hydrochloric acid generation neutralization reaction, but this neutral effectiveness can only temporarily be lived in peace with each other, and hydrochloric acid in gastric juice again can supersecretion soon, if neutralize repeatedly with alkaline medicine again, can cause that more hydrochloric acid in gastric juice secretes in a large number, be as good as and add fuel to the flames.This is because this class medicine can only neutralize and be secreted into the hydrochloric acid in gastric juice of gastral cavity, result's gastral cavity pH value at short notice raises rapidly, this has weakened the effect of the negative feedback inhibition gastric acid secretion of hydrochloric acid in gastric juice on the contrary, make parietal cell generate more hydrochloric acid in gastric juice, cause " knock-on ", so antacid only is used as the adjuvant drug of ulcer treatment at present.
The receptor blocking agent therapy:
In vivo, have three kinds of materials can directly act on parietal cell, promote the generation and the secretion of hydrochloric acid in gastric juice, they are respectively: vagusstoff, gastrin, histamine.When it is found that these three kinds of physiological stimuluss all are to act on the acceptor on the parietal cell film and behind the gastric acid secretion, just attempt to seek corresponding receptor blocking agent, the acceptor with on the blocking-up parietal cell film reduces the generation of hydrochloric acid in gastric juice.Being used for clinical the earliest is cholinergic receptor blocker coromegine (atropine).Coromegine can only reduce the generation of a part of hydrochloric acid in gastric juice, and the patient is effective to part.But, thereby side effects such as dry, the dimness of vision are arranged because of coromegine also acts on the m receptor of body other parts simultaneously.In recent years, the discovery of specific M receptor blocker pirenzepine (pirenzepine) has substituted atropinic use, and effect is better than coromegine.H receptor blocker mainly contains medicines such as Cimitidine Type A/AB, Ranitidine HCL, famotidine, nizatidine, roxatidine, and they are by the secretion of blocking-up parietal cell H2 acceptor and gastric acid inhibitory, has characteristics such as determined curative effect, untoward reaction are few, economical and practical.Though gastrin-receptor is still at the experimental stage at present through seeking for many years, is not used in clinical treatment.Because three kinds of stimuluss independently play a role by each autoreceptor, thereby the use receptor blocking agent is treated, can only be to a certain extent or only effective to a part of patient.
Proton pump inhibitor (PPI) therapy:
Because proton pump is the final step that produces hydrochloric acid in gastric juice, thereby reducing the effective means of hydrochloric acid in gastric juice is the activity that suppresses proton pump.Yan Zhi proton pump inhibitor such as omeprazole (Omeprazole) can directly act on proton pump in recent years, suppress the effect of its secretion hydrochloric acid in gastric juice.Omeprazole has been widely used in clinical treatment abroad, and effect is fine.But because stomach ulcer is a kind of chronic disease, and sour pump metabolism is very fast, must adhere to taking for a long time omeprazole, and this causes treating the cost costliness, has exceeded many patients' ability to bear, and therefore, this medicine also is not suitable for extensive at home clinical use.
Eradicate the pharmacological agent of Hp:
Should accept the eradication therapy of Hp to Hp male ulcer, main therapy is to unite to use microbiotic and antacid.Microbiotic such as clarithromycin, amoxycilline Trihydrate bp, tinidazole etc. play antibacterial or germicidal action, but these microbiotic are all not acidproof, and its drug effect depends on the pH value; Acid inhibitor such as PPI can provide a suitable pH environment, and many acid nonfast microbiotic will be brought into play maximum effectiveness under this environment.
Chronic gastritis also is a kind of common disease, frequently-occurring disease, and it is the first that its sickness rate occupy in various stomach trouble, accounts for outpatient service gastroscopy patient's 90%, and the age is big more, and sickness rate is high more, and particularly middle-older patient more more sees.The general treatment method of chronic gastritis normally adopts the proton pump inhibitor treatment, reduces the stimulation of hydrochloric acid in gastric juice to stomach mucous membrane, mitigation symptoms; Or the pharmacological agent of colloidal bismuth class, this type of medicine is owing to its colloid property, and the protein binding that can ooze out with mucous membrane under sour environment still forms firm protective at stomach mucous membrane together; Or antibiotics or other non-medicine assisting therapy etc.(referring to: 1, Zhang Yan, the treatment present situation of chronic gastritis, the 24th the 4th phase of volume of Li Ganzhi's journal; 2, Guo Shoujun, the diagnosis and treatment of chronic gastritis, Chinese clinic study magazine, the 13rd the 2nd phase of volume of January in 2007).
In sum, diseases such as hyperchlorhydria, peptide ulceration, chronic gastritis are common frequently-occurring disease, and their treatment need reduce acidity in the stomach mostly, and continuing to seek safely and effectively, the broad-spectrum curing medicine is still the problem that needs solve.The contriver is through experimental study for many years, find that unexpectedly a kind of Herba Erodii extract has the activity of good restraining gastric acid secretion, reduction gastric acidity, aspect the diseases such as treatment or prevention hyperchlorhydria, peptide ulceration, chronic gastritis good effect is being arranged, and finishing the present invention based on above discovery.
Summary of the invention
One aspect of the present invention provides a kind of new Herba Erodii extract, and the per-cent that the corilagin of described Herba Erodii extract Chinese style I accounts for the extract total mass is 5%-25%, preferred 15%-25%, most preferably 20%.
The present invention provides the preparation method of described Herba Erodii extract on the other hand, it is characterized in that, Herba Erodii (Geranium dahuricum) is pulverized the alcohol reflux that 5-8 doubly measures 2-4 time, extracting solution merges concentrated, after being dissolved in water, organic solvent extraction, extracting solution is concentrated into dried, column chromatography for separation, the chloroform methanol of different ratios is an eluent, collects chloroform: the elutriant of methyl alcohol=5: 1 merges, and is concentrated into and does promptly.Wherein said organic solvent is selected from sherwood oil, ethyl acetate.
Concrete preparation method is: Herba Erodii (Geranium dahuricum) is pulverized, add 5-8 and doubly measure 40% ethanol, refluxing extraction 2-4 time, elimination dregs of a decoction united extraction liquid, concentrate medicinal extract, after being dissolved in water, use sherwood oil successively, ethyl acetate extracts, and acetic acid ethyl acetate extract is evaporated to dried, divide and pull on silicagel column, use chloroform successively, chloroform: methyl alcohol=10: 1, chloroform: methyl alcohol=8: 1, chloroform: methyl alcohol=5: 1 carries out wash-out, with chloroform: the elutriant of methyl alcohol=5: 1 merges, and is concentrated into driedly, obtains containing the Herba Erodii extract of corilagin.
The preparation method is more specifically: get Herba Erodii (Geranium dahuricum) and pulverize, add the ethanol of 8 times of amounts 40%, refluxing extraction three times, each 2 hours.The elimination dregs of a decoction merge No. 3 extracting solutions, and concentrating under reduced pressure gets medicinal extract, add the suitable quantity of water dissolving after, extract with sherwood oil, ethyl acetate successively.Acetic acid ethyl acetate extract is evaporated to dried, divides and to pull on silicagel column (100-200 order silica gel G), use chloroform successively, chloroform: methyl alcohol=10: 1, chloroform: methyl alcohol=8: 1, chloroform: methyl alcohol=carry out wash-out at 5: 1, detect with thin layer chromatography.With chloroform: the elutriant of methyl alcohol=5: 1 merges, and is concentrated into driedly, obtains the described Herba Erodii extract that contains corilagin, and wherein the content of corilagin is 5%-25%.
Further aspect of the present invention provides described Herba Erodii extract gastric acid inhibitory secretion, reduces the purposes of gastric acidity.
Further aspect of the present invention provides described Herba Erodii extract treatment or prevents the purposes of diseases such as hyperchlorhydria, peptide ulceration, chronic gastritis.
Further aspect of the present invention provides a kind of gastric acid inhibitory secretion that is used for, and reduces the pharmaceutical composition of gastric acidity, and it comprises described Herba Erodii extract and one or more acceptable accessories.
Further aspect of the present invention provides a kind of pharmaceutical composition that is used for the treatment of or prevents diseases such as hyperchlorhydria, peptide ulceration, chronic gastritis, and it comprises described Herba Erodii extract and one or more acceptable accessories.
Herba Erodii described in the present invention mainly is selected from one or more the plant in thick root Herba Erodii (Geranium dahuricum) in the Mang ox seedling section plant, Carolina Cranesbill Herb (Geranium caroliniznum), Herba Geranii eriostemonis (Geranium eriostemon), suede back of the body Herba Erodii (Geranium vlassorianum), Qingdao Cranesbill (Geranium tsingtauense), the Robetium macrorrhizum (Geranium macrorrhizum).
The content of corilagin adopts high performance liquid chromatography to detect in the Herba Erodii extract provided by the invention, and actual conditions and method are as follows:
Instrument: high performance liquid chromatograph
Pump: Tianjin, island LC-10AT vp
Detector: Tianjin, island SPD-10A vp
Workstation: the NC2000 of Zhejiang University
Moving phase: acetonitrile-1% phosphoric acid solution (13: 87)
Wavelength X: 268nm
Chromatographic column: Themo Hypersil BDS C18 (4.6 * 250mm, 5 μ m)
Flow velocity: 1.0ml/min
Column temperature: 30 ℃
Reference substance: corilagin (making according to the method among the Chinese patent ZL97104154.7), area normalization content is 95%
Method of calculation: the about 20 μ g/ml of reference substance solution concentration (C to) prepare the about 100 μ g/ml of strength of solution to be measured (C sample), sample size 20 μ l, record reference substance solution peak area (A to), solution peak area to be measured (A sample)
Pharmaceutical composition provided by the invention can be Herba Erodii extract and the mixing acceptable accessories that contains corilagin, pharmaceutical preparation technology according to routine, the any pharmaceutical preparation of use, for example capsule, tablet, pill, granule, the oral liquid etc. clinically of being fit to that are prepared into.
Acceptable accessories comprises pharmaceutically acceptable weighting agent, disintegrating agent, tackiness agent and lubricant, correctives etc.
Suitable weighting agent is selected from lactose, Microcrystalline Cellulose, pregelatinized Starch, starch, dextrin, N.F,USP MANNITOL, Mierocrystalline cellulose, sucrose, glucose, sorbyl alcohol, Xylitol etc.
Suitable disintegrants is selected from polyvinylpolypyrrolidone, sodium starch glycolate, low-substituted hydroxypropyl cellulose, crosslinked Vltra tears etc.
Suitable binder is selected from polyvidone, hydroxypropylcellulose, methylcellulose gum, Xylo-Mucine, Vltra tears, ethyl cellulose etc.
Examples of suitable lubricants is selected from micropowder silica gel, Magnesium Stearate, Zinic stearas, calcium stearate, stearic acid, refining hydrogenated vegetable oil, palmitinic acid, talcum powder, polyoxyethylene glycol, sodium lauryl sulphate, Stepanol MG etc.
Suitable correctives is selected from sucrose, simple syrup, glycerine, sorbyl alcohol, N.F,USP MANNITOL, stevioside, soluble saccharin etc.
Peptide ulceration of the present invention comprises stomach ulcer and duodenal ulcer.
The present invention is by ligation rat pylorus, collect 6 hours excretory gastric juice and estimate the described influence that contains the Herba Erodii extract of corilagin to gastric acid secretion, test-results shows that described Herba Erodii extract can effectively suppress the gastric acid secretion of rat, reduces gastric acidity.When the result of treatment of estimating peptide ulceration, adopt following three kinds of experimental animal models: pyloric ligation ulcers rat gastric ulcer model, water logging irritability rat gastric ulcer model, the acetate type rat gastric ulcer model of burning.Wherein, pylorus ligature law is a Shay ' s traditional classical rat gastric ulcer modelling, and behind the ligation pylorus, gastric juice is detained in the stomach, and the coat of the stomach defence capability weakens, and causes stomach ulcer to form.Microscopically is observed and is seen leukocyte infiltration and tissue necrosis, and ulcer reaches the flesh layer deeply.This model is similar to the stomach ulcer that human hyperchlorhydria causes.The modeling mechanism of water logging irritability rat gastric ulcer model is, after animal was subjected to stress stimulation, the sympathetic nervous system excitability raise, and vasoconstriction causes the mucous membrane hypoxic-ischemic, and resistibility descends.Parasympathetic nerve-hypophysis-adrenal system is excited to raise, and causes that hydrochloric acid in gastric juice, stomach en-and gastrin secretion increase, thereby causes stress ulcer.The acetate method is directly burnt the stomach serous coat with acetate and is formed ulcer, and this method is reliable, good reproducibility, and ulcer is dark and big, and is very similar to the mankind's chronic gastric ulcer.Its normal healing needs about 60 days, individual animal is also arranged in still disunion more than 200 days, thereby is applicable to the effect of observing medicine promotion ulcer healing, can be used as the experimental model of screening treatment chronic gastric ulcer medicine.
Animal test results shows: the Herba Erodii extract that contains corilagin provided by the invention can reduce gastric acid secretion, reduces ulcer incidence and the ulcer index of rat in pyloric ligation ulcers and the water logging stress gastric ulcer model; And the healing of rat gastric ulcer in the acetate burn type gastric ulcer model had significant promoter action, and can increase the ulcer healing percentage, reduce ulcer index.
The Herba Erodii extract preparation technology who contains corilagin provided by the invention is simple, and can reduce gastric acid secretion, reduce gastric acidity, reduce the incidence and the ulcer index of ulcer, have good curing or the prevention peptide ulceration effect, and can be prepared into easily according to the ordinary method of this area the treatment peptide ulceration pharmaceutical composition for clinical use.
Embodiment
Describe content of the present invention in detail with specific embodiment below, following examples also do not mean that any limitation of the invention.
Embodiment 1 preparation contains the Herba Erodii extract of corilagin
Get thick root Herba Erodii (Geranium dahuricum) 2000g, pulverize, add the ethanol of 8 times of amounts 40%, refluxing extraction three times, each 2 hours.The elimination dregs of a decoction merge No. 3 extracting solutions, and concentrating under reduced pressure gets medicinal extract 280g, add the suitable quantity of water dissolving after, use sherwood oil (500ml * 4), ethyl acetate (500ml * 4) to extract successively.Acetic acid ethyl acetate extract is merged, be evaporated to driedly, divide and pull on silicagel column (silica gel with 100～200 purpose silica gel G), use chloroform successively, chloroform: methyl alcohol=10: 1, chloroform: methyl alcohol=8: 1, chloroform: methyl alcohol=carry out wash-out at 5: 1, adopt thin layer chromatography to follow the tracks of and detect.With chloroform: the elutriant of methyl alcohol=5: 1 merges, and is concentrated into driedly, obtains containing the Herba Erodii extract 25g of corilagin, and detecting wherein with high performance liquid chromatography, the content of corilagin is 20%.
Embodiment 2 preparations contain the Herba Erodii extract of corilagin
Get Qingdao Cranesbill (Geranium tsingtauense) 2000g, pulverize, add the ethanol of 8 times of amounts 40%, refluxing extraction twice, each 2 hours.The elimination dregs of a decoction merge No. 2 extracting solutions, and concentrating under reduced pressure gets medicinal extract 220g, add the suitable quantity of water dissolving after, use sherwood oil (500ml * 4), ethyl acetate (500ml * 4) to extract successively.Acetic acid ethyl acetate extract is merged, be evaporated to driedly, divide and pull on silicagel column (silica gel with 100～200 purpose silica gel G), use chloroform successively, chloroform: methyl alcohol=10: 1, chloroform: methyl alcohol=8: 1, chloroform: methyl alcohol=carry out wash-out at 5: 1, adopt thin layer chromatography to follow the tracks of and detect.With chloroform: the elutriant of methyl alcohol=5: 1 merges, and is concentrated into driedly, obtains containing the Herba Erodii extract 18g of corilagin, and detecting wherein with high performance liquid chromatography, the content of corilagin is 25%.
Embodiment 3 preparations contain the Herba Erodii extract of corilagin
Get suede back of the body Herba Erodii (Geranium vlassovianum) 2000g, pulverize, add the ethanol of 5 times of amounts 40%, refluxing extraction four times, each 2 hours.The elimination dregs of a decoction merge No. 4 extracting solutions, and concentrating under reduced pressure gets medicinal extract 250g, add the suitable quantity of water dissolving after, use sherwood oil (500ml * 4), ethyl acetate (500ml * 4) to extract successively.Acetic acid ethyl acetate extract is merged, be evaporated to driedly, divide and pull on silicagel column (silica gel with 100～200 purpose silica gel G), use chloroform successively, chloroform: methyl alcohol=10: 1, chloroform: methyl alcohol=8: 1, chloroform: methyl alcohol=carry out wash-out at 5: 1, adopt thin layer chromatography to follow the tracks of and detect.With chloroform: the elutriant of methyl alcohol=5: 1 merges, and is concentrated into driedly, obtains containing the Herba Erodii extract 16g of corilagin, and detecting wherein with high performance liquid chromatography, the content of corilagin is 6%.
Embodiment 4
Contain of the influence of the Herba Erodii extract of corilagin to rat tolerance secretion
1 material
1.1 reagent
Herba Erodii extract makes according to the method for embodiment 1
Ranitidine hydrochloride is provided by Jiangxi Huiren Pharmaceutical Co., Ltd
Omeprazole is provided by AstraZeneca pharmaceutical Co. Ltd
Xylo-Mucine (CMC-Na) is provided by Chemical Reagent Co., Ltd., Sinopharm Group
Benzylpenicillin sodium for injection is provided by Huabei Pharmaceutic Co., Ltd
Chloral Hydrate is provided by Chemical Reagent Co., Ltd., Sinopharm Group
Sodium hydroxide is provided by Nanjing chemical reagent one factory
Phenolphthalein cause Nereid analyses Chemical Industry Science Co., Ltd to be provided
1.2 animal
Cleaning level SD rat, male, body weight 180-200g, Shanghai Slac Experimental Animal Co., Ltd.
1.3 instrument
Sartorius BS110S electronic balance Beijing Sai Duolisi balance company limited
LDZ5-2 whizzer Beijing Medical Centrifugal Machine Factory
1.4 group and drug dose setting
Model group CMC-Na (0.5%)
Ranitidine HCL group 100mg/kg
Omeprazole group 13.6mg/kg
Herba Erodii extract 200mg/kg
Herba Erodii extract 100mg/kg
1.5 medicine preparation and route of administration: medicine is with CMC-Na (0.5%) suspendible, gastric infusion, 10ml/kg.
2 methods
2.1 modeling method
Each organizes the rat oral gavage administration, and 1 time/d, continuous 5d.Fasting 48h before the experiment.During experiment with rat with Chloral Hydrate (0.30g/kg) anesthesia, carry out pyloric ligation, and duodenal administration 1 time, water is prohibited in the postoperative fasting, puts to death animal behind the 6h, collects gastric juice in graduated centrifuge tube.With 3000r/min, centrifugal 15min gets supernatant liquor.
2.2 observation index
2.2.1 gastric juice amount
Behind the modeling 6h, put to death rat, collect gastric juice in graduated centrifuge tube.With 3000r/min, centrifugal 15min gets supernatant liquor, accurately measures the gastric juice volume.
2.2.2 total acidity
Behind the modeling 6h, put to death rat, collect gastric juice in graduated centrifuge tube.With 3000r/min, centrifugal 15min gets supernatant liquor, measures total acidity with 0.01mol/L NaOH by acid base neutralization titration (phenolphthalein is indicator), and calculates total acid output according to gastric secretion.
2.3 statistical procedures
Data are represented with X ± SD, carry out statistical procedures with SPSS11.0, relatively use the least significant difference method in twos between each group.
3. experimental result
Table 1. Herba Erodii extract is to pylorus ligation rat gastric juice excretory influence (X ± SD)
Annotate: compare with the blank group,
*P＜0.05,
*P＜0.01.
4 conclusions
Herba Erodii extract can reduce rat total acidity gastric juice and total acid output, and the prompting Herba Erodii extract has the effect of gastric acid inhibitory excretory, can be used for the treatment of hyperchlorhydria, chronic gastritis.
Embodiment 5 contains the anti-gastric-ulcer experimentation on animals of the Herba Erodii extract of corilagin
1 experiment material:
1.1 animal:
The SD rat, male, 180-220g is provided by the Yangzhou University experimental center
1.2 medicine and reagent:
Herba Erodii extract: the method according to embodiment 1 makes
Positive drug: ranitidine hydrochloride capsules is provided by middle promise pharmaceutcal corporation, Ltd
Acetate: Shanghai is insulted wind chemical reagent company limited and is provided
Vetanarcol: Chinese Medicine Shanghai chemical reagents corporation provides
1.3 equipment:
The rat retaining plate, operating scissors, scalpel, tweezers, needle holder, microsyringe, balance
1.4 experiment condition:
The experimental rat sub-cage rearing is fed and is raised full-valence pellet feed, freely drinks water 20 ± 2 ℃ of room temperatures, humidity 50-70%
2. pyloric ligation ulcers rat gastric ulcer model
2.1 experimental technique
Rat is divided into 4 groups at random by body weight, 10 every group: blank group, Ranitidine HCL group (135mg/kg), Herba Erodii extract high dose group (150mg/kg), Herba Erodii extract low dose group (75mg/kg).According to the continuous gastric infusion of 10ml/kg 5 days, the blank group gave equivalent distilled water to administration group rat respectively.Rat begins fasting and can't help water after the 1st administration, the last administration after 2 hours with rat with 0.7ml/ 1% shallow fiber crops of vetanarcol only, from ensiform process of sternum lower edge ventrimeson open abdomen, the about 2-3cm of otch.At costal margin position, left side, up one push away gently with referring to, make stomach be exposed to otch.Wear a line (not injuring blood vessel) with pylorus ligation (other vascular ligations that will not be close to) under the stomach pylorus, sew up incision of abdominal wall, clean with physiological saline, iodine disinfection is with bundle cutting mouth.Fasting is put to death animal after prohibiting water 18h, opens the abdominal cavity, behind the ligation orifice of the stomach stomach is taken out.Collect gastric juice, volume calculated.Cut off stomach along greater gastric curvature,, be tiled on the blank sheet of paper, observe the situation that glandular stomach portion ulcer takes place, write down every group of ulcerogenic mouse number, ulcer number, ulcer level, ulcer area and pathology situation, calculate ulcer index with physiological saline flush away gastric content.
The ulcer index assessment method: the rat that gastric perforation do not occur is calculated ulcer index with aphtha number and ulcer area.Calculate the area summation that all maximum diameters surpass the ulcer of 1mm, the area of each ulcer is according to S=π * r
1* r
2Calculate r
1And r
2Be respectively diameter and wide footpath; All count according to aphtha less than the ulcer of 1mm in diameter and wide footpath, with aphtha number and the ulcer total area as the Comprehensive Assessment index.Evaluation criteria sees the following form:
| Ulcer index | 0 | 1 | 2 | 3 | 4 | 5 | 6 |
| The aphtha number | 0 | 1-5 | 6-30 | 31-60 | ＞60 | ||
| Ulcer area mm 2 | 0 | 1-10 | 11-20 | 21-30 | 31-40 | 41-50 | ＞50 or the perforation |
Ulcer suppresses percentage %=(blank group ulcer index-medication group ulcer index)/blank group ulcer index * 100%
The ulcer incidence: the number of animals that ulcer takes place accounts for the per-cent of laboratory animal number.
2.2 experimental result
To the influence of pyloric ligation ulcers stomach ulcer (X ± s)
| Group | Dosage mg/kg | Number of animals | Ulcer index | Ulcer suppresses percentage % | Ulcer incidence % | Gastric juice volume ml |
| Blank | - | 10 | 3.9±1.7 | 100 | 18.8±3.0 | |
| Ranitidine HCL | 135 | 10 | 1.5±1.0 ** | 61.5 | 80 | 14.6±4.5 * |
| Herba Erodii extract | 150 | 10 | 0.9±1.1 ** | 76.9 | 50 | 9.7±3.5 ** |
| Herba Erodii extract | 75 | 10 | 2.2±0.9 * | 43.6 | 100 | 14.3±4.2 * |
Compare with the blank group
*Represent P＜0.05,
*Represent P＜0.01;
Above result shows: form tangible ulcer behind the rat pylorus ligation in this experiment, show the modeling success.Positive control medicine Ranitidine HCL can reduce gastric acid secretion, reduces the incidence and the ulcer index of ulcer.The high and low dose of Herba Erodii extract can both reduce gastric acid secretion, reduces the incidence and the ulcer index of ulcer.Herba Erodii extract reduces gastric acid secretion when high dosage, effects such as the incidence of reduction ulcer and ulcer index are better than the Ranitidine HCL group.
3 water logging irritability rat gastric ulcer models
3.1 experimental technique
Rat is divided into 4 groups at random by body weight, 10 every group: blank group, Ranitidine HCL group (135mg/kg), Herba Erodii extract high dose group (150mg/kg), Herba Erodii extract low dose group (75mg/kg).Rat was pressed the continuous gastric infusion of 10ml/kg 5 days, the blank group gives equivalent distilled water, and last administration rat fasting in preceding 24 hours was fixed in the four limbs colligation of rat on the plank after the administration in 1 hour, be dipped in the tank about 20 ℃, liquid level remains on the ensiform process of sternum level.Put to death rat after 20 hours, open the abdominal cavity, behind ligation orifice of the stomach and the pylorus stomach is taken out, in stomach, inject 1% formaldehyde solution 10ml, and stomach was immersed in 1% formaldehyde solution 10 minutes, fixedly ectonexine by pylorus.Cut off stomach along greater gastric curvature,, be tiled on the blank sheet of paper, observe the situation that glandular stomach portion ulcer takes place with physiological saline flush away gastric content.The degree of ulcer is represented with ulcer index, and the incidence of calculating ulcer inhibition percentage and ulcer is estimated the effect of medicine.
Ulcer index: the major diameter of ulcer is directly measured length greater than 1mm person, and every 1mm is 1 minute; If then score greater than 1mm person and double in wide footpath, for major diameter and wide footpath all less than 1mm person, by the score of ulcer number, each ulcer meter 0.5 minute.The accumulative total total points of every animal is the ulcer index of this animal.
Ulcer suppresses percentage %=(blank group ulcer index-medication group ulcer index)/blank group ulcer index * 100%
The ulcer incidence: the number of animals that ulcer takes place accounts for the per-cent of experimental animal number.
3.2 experimental result
To the influence of water logging stress gastric ulcer model (X ± s)
| Group | Dosage (mg/kg) | Number of animals | Ulcer index | Ulcer suppresses percentage % | Ulcer incidence % |
| Blank | - | 10 | 11.9±5.4 | 0 | 100 |
| Ranitidine HCL | 135 | 10 | 2.6±1.9 ** | 78.2 | 80 |
| Herba Erodii extract | 150 | 10 | 2.3±2.3 ** | 80.7 | 80 |
| Herba Erodii extract | 75 | 10 | 6.6±2.8 * | 44.5 | 100 |
Compare with the blank group
*Represent P＜0.05,
*Represent P＜0.01;
Experimental result shows: formed tangible stomach ulcer after the rat water logging in this experiment, shown the modeling success.Positive control medicine Ranitidine HCL has the obvious suppression effect to ulceration, and can significantly reduce ulcer index.Close during the Herba Erodii extract high dosage with the action effect of Ranitidine HCL, the ulceration of irritability rat gastric ulcer model is had restraining effect, and dose-effect relationship is obvious, the high dose group effect is better than low dose group.
The 4 acetate type rat gastric ulcer model of burning
4.1 experimental technique
Rat is divided into 4 groups at random by body weight, 10 every group: blank group, Ranitidine HCL group (135mg/kg) Herba Erodii extract high dose group (150mg/kg), Herba Erodii extract low dose group (75mg/kg).The rat fasting after 24 hours, is carried out intraperitoneal injection of anesthesia with 5mg/100g body weight vetanarcol, then its dorsal position is fixed on the operating table.Cut the stomach wall hair, use the alcohol routine disinfection, under xiphoid-process to the about 2cm of lower edge ventrimeson clip, stomach is shifted out the abdominal cavity, at the facies ventralis of stomach, body of stomach and pyloric antrum intersection, thrust 0.4-0.5mm under the serous coat with microsyringe is flat, inject the acetate of 50 μ l10%, form papule.Stomach is sent back to gently, sew up abdominal muscle, skin suture then.With the tincture of iodine, alcohol disinfecting, the conventional raising.From performing the operation next day, each organizes every day by the 10ml/kg gastric infusion, successive administration 7 days, and the blank group is given equivalent distilled water.Animal was all put to death in the 7th day.Open fu jie and prick pylorus and orifice of the stomach, get stomach and be dipped in 1% formaldehyde solution, fix 10 minutes.Cut off along greater gastric curvature, stomach is turned up, outwell content, wash out swill gently with the nipple suction pipe again.Ulcer is rounded or oval, and central concave is swelled all around slightly, and capillary vessel gathers.The ulcer that has healed has protuberance on every side slightly, and the surface is ruddy, and as seen radial microgroove is arranged.With the equal value representation ulcer index of the major diameter of ulcer and minor axis, carry out statistical procedures to calculate the ulcer healing percentage, the evaluation medicine is to the promoter action of ulcer healing.
Ulcer healing percentage (%)=(blank group ulcer diameter average summation-medication group ulcer diameter average summation)/blank group ulcer diameter average summation * 100%
4.2 experimental result
To the burn influence (X ± s) of type stomach ulcer of rats acetic acid
| Group | Dosage mg/kg | Number of animals | Ulcer index mm | Ulcer healing percentage % |
| The blank group | - | 10 | 5.5±1.6 | |
| Ranitidine HCL | 135 | 10 | 3.2±1.5 ** | 41.8 |
| Herba Erodii extract | 150 | 10 | 2.8±1.3 ** | 49.1 |
| Herba Erodii extract | 75 | 10 | 4.3±1.8 | 21.8 |
Compare with the blank group
*Represent P＜0.05,
*Represent P＜0.01;
Healing to rat gastric ulcer during the Herba Erodii extract high dosage has significant promoter action, can increase the ulcer healing percentage, reduces ulcer index, and effects such as the incidence of reduction ulcer and ulcer index are all near with the Ranitidine HCL winding.Little during low dosage to the influence of ulcer healing and ulcer index.
Claims (6)
1. Herba Erodii extract, it is characterized in that adopting following method preparation: Herba Erodii is pulverized, doubly measure 40% alcohol reflux 2-4 time with 5-8, extracting solution merges concentrated, after being dissolved in water, use sherwood oil, ethyl acetate extraction respectively, acetic acid ethyl acetate extract is concentrated into dried, divide and pull on silicagel column, use chloroform successively, chloroform: methyl alcohol=10: 1, chloroform: methyl alcohol=8: 1, chloroform: methyl alcohol=5: 1 carries out wash-out, and with chloroform: the elutriant of methyl alcohol=5: 1 merges, and is concentrated into and does promptly.
2. the preparation method of the described Herba Erodii extract of claim 1, it comprises the steps: Herba Erodii is pulverized, add 5-8 and doubly measure 40% ethanol, refluxing extraction 2-4 time, elimination dregs of a decoction united extraction liquid, concentrate medicinal extract, after being dissolved in water, use sherwood oil successively, ethyl acetate extracts, acetic acid ethyl acetate extract is evaporated to dried, divides and to pull on silicagel column, use chloroform successively, chloroform: methyl alcohol=10: 1, chloroform: methyl alcohol=8: 1, chloroform: methyl alcohol=5: 1 carries out wash-out, and with chloroform: the elutriant of methyl alcohol=5: 1 merges, be concentrated into driedly, obtain Herba Erodii extract.
The described Herba Erodii extract of claim 1 in preparation gastric acid inhibitory secretion, reduce the purposes in the medicine of gastric acidity.
4. the purposes of the described Herba Erodii extract of claim 1 in the medicine of preparation treatment or prevention hyperchlorhydria, peptide ulceration, chronic gastritis.
5. one kind is used for the pharmaceutical composition that gastric acid inhibitory is secreted, reduced gastric acidity, and it contains the described Herba Erodii extract of claim 1, and one or more acceptable accessories.
6. pharmaceutical composition that is used for the treatment of or prevents hyperchlorhydria, peptide ulceration, chronic gastritis, it contains the described Herba Erodii extract of claim 1, and one or more acceptable accessories.
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| CN111269277B (en) * | 2020-04-07 | 2023-02-28 | 云南农业大学 | Method for extracting and separating isocorilagin from Geranium strictipes |
| CN112451534B (en) * | 2020-10-12 | 2021-09-17 | 中国医学科学院医药生物技术研究所 | Application of corilagin in inhibiting coronavirus replication to exert anti-coronavirus medicinal function |
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| 李琳波，等.青岛老鹳草化学成分的研究.《中草药》.2000,第31卷(第2期),92-93. * |
| 杜树山,等.毛蕊老鹳草化学成分研究.《中国中药杂志》.2003,第28卷(第7期),625-626. * |
| 杜树山，等.毛蕊老鹳草水溶性化学成分研究.《中草药》.2003,第34卷(第6期),501-502. * |
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