CN101461816B - Novel use of corilagin - Google Patents
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- CN101461816B CN101461816B CN2008101292872A CN200810129287A CN101461816B CN 101461816 B CN101461816 B CN 101461816B CN 2008101292872 A CN2008101292872 A CN 2008101292872A CN 200810129287 A CN200810129287 A CN 200810129287A CN 101461816 B CN101461816 B CN 101461816B
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Abstract
The invention relates to novel application of corilagin or a pharmaceutically acceptable corilagin salt, in particular to application of the corilagin or the pharmaceutically acceptable corilagin salt in treating or preventing diseases related to gastric acid hypersecretion such as hyperchlorhydria, peptic ulcer and chronic gastritis.
Description
Technical field
The present invention relates to the new purposes of corilagin or its officinal salt, relate to the purposes of treatment of corilagin or its officinal salt or prevention gastroxia relevant disease particularly, as diseases such as hyperchlorhydria, peptic ulcer, chronic gastritiss.
Background technology
Hyperchlorhydria is meant gastric juice (comprising compositions such as hydrochloric acid and pepsin) supersecretion, and makes the patient feel stomach discomfort, acid regurgitation water, heartburn (stomach burn feeling).Slight hyperchlorhydria mainly shows as and occurs stomach burn feeling, acid regurgitation repeatedly, if hyperchlorhydria infringement gastric mucosa, also can cause stomachache, feel sick, symptom such as vomiting, hyperchlorhydria also may be further developed into peptic ulcer, even perforated ulcer occurs.
The medicine of hyperchlorhydria can be divided three classes: the first kind be in and the gastric acid medicine, as sodium bicarbonate, aluminium hydroxide etc.; Second class is for pressing down sour medicine, as cimetidine, ranitidine, famotidine and proton pump inhibitor etc.; The 3rd class is for increasing the medicine of gastric mucosal defense ability, as bismuth preparation etc.
Peptic ulcer is a kind of global commonly encountered diseases and frequently-occurring disease, estimates that about 10% crowd was once suffering from this disease in life.Peptic ulcer means gastric ulcer and duodenal ulcer, it is a kind of multi-pathogenesis disease, its morbidity is relevant with multiple factor, as gastric acid, pepsin, Helicobacter pylori infection, heredity, body constitution, environment, diet, living habit, neural Nervous and Mental Factors 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.Wherein, the effect of gastric acid one pepsic invasion and attack effect, especially gastric acid occupies critical role in ulcer, and academia has the judgement of " anacidity does not just have ulcer " always.The treatment ulcer mainly is the secretion of gastric acid inhibitory, reduces the damage of gastric acid to stomach, duodenal mucosa, promotes the healing of ulcer surface.Along with people to the deepening continuously of gastric acid generting machanism understanding, to the Therapeutic Method of peptic ulcer also update (referring to: the time space, the treatment of gastric ulcer and gastric acid secretion, biology circular, 1994,29 (12), 14-15).
Antiacid therapy:
In early days, people recognize that the formation of ulcer is relevant with hyperchlorhydria, so want to treat ulcer with antacid.Generally be to take alkalescent medicine, as in the sodium bicarbonate etc. and gastric acid, but neutral effectiveness can only temporarily live in peace with each other, and gastric acid again can supersecretion soon, if reuse alkalescence medicine neutralizes repeatedly, can cause that more gastric acid secretes in a large number, is as good as and adds fuel to the flames.This is because this class medicine can only neutralize and be secreted into the gastric acid 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 gastric acid on the contrary, make parietal cell generate more gastric acid, cause " knock-on ", present this Therapeutic Method is eliminated basically.
The receptor blocking therapy:
In vivo, have three kinds of materials can directly act on parietal cell, promote the generation and the secretion of gastric acid, they are respectively: acetylcholine, gastrin, histamine.When it is found that these three kinds of physiological stimulating factors all are to act on the receptor on the parietal cell film and behind the gastric acid secretion, just attempt to seek corresponding receptor blocking agent, the receptor with on the blocking-up parietal cell film reduces the generation of gastric acid.Being used for clinical the earliest is cholinoceptor blocker atropine (atropine).Atropine can only reduce the generation of a part of gastric acid, and the patient is effective to part.But, thereby side effect such as xerostomia, the dimness of vision are arranged because of atropine 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 atropine.H receptor blocker mainly contains medicines such as cimetidine, ranitidine, famotidine, nizatidine, roxatidine, and they are by blocking-up parietal cell H
2The secretion of receptor 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 stimulating factors 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.
Suppress the proton pump therapy:
Because proton pump is the final step that produces gastric acid, thereby reducing the effective method of gastric acid 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 gastric acid.Omeprazole has been widely used in clinical treatment abroad, and effect is fine.But because peptic ulcer is a kind of chronic disease, and sour pump metabolism is very fast, must adhere to taking for a long time magnesium difficult to understand and draw azoles, 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.
Chronic gastritis also is a kind of commonly encountered diseases, frequently-occurring disease, and it is the first that its sickness rate occupy in various gastropathy, 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 gastric acid to gastric mucosa, mitigation symptoms; Or colloidal bismuth class Drug therapy, this type of medicine is owing to its colloid property, and the protein binding that can ooze out with mucosa under sour environment still forms firm protective at gastric mucosa together; Or antibiotics or other non-medicine auxiliary treatment 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, adopt reduction gastric acidity, the excretory medicine of gastric acid inhibitory to carry out Primary Care mostly for diseases such as hyperchlorhydria, peptic ulcer, chronic gastritiss clinically at present, normally used is proton pump inhibitor, because the above-mentioned shortcoming of proton pump inhibitor, seek determined curative effect, side effect is little, the medicine that is fit to extensive clinical use is still a problem that waits to solve.The inventor is through experimentation for many years, find that unexpectedly corilagin has good restraining gastric acid secretion effect, under doses, the excretory effect of its gastric acid inhibitory is not second to proton pump inhibitor, therefore, the gastroxia relevant disease there is effect preferably, as diseases such as hyperchlorhydria, peptic ulcer, chronic gastritiss; Especially the gastric ulcer experimental animal model there is better curative effect, finishes the present invention based on above discovery.
Corilagin (corilagin) claims the Fructus Chebulae inferior tan element, corilagin etc. again, chemistry 1-O-Galla Turcica (Galla Helepensis) acyl-3 by name, and 6-O-hexahydroxy biphenyl two formyls-β-D-glucose are naturally occurring polyhydroxy Hydrolysable Tannins with labyrinth.It is present in the various plants, as phyllanthus plant (Cacumen Securinegae Suffruticosae, close Citrus chachiensis Hort. grass), Mang cattle Seedling platymiscium, Geranium plant, euphorbia, Herba Acalyphae platymiscium, pomegranate platymiscium, Acer plant or Terminalia plant etc.Up to now, corilagin has had multiple biological activity to be reported in succession.
The antihypertensive activity of corilagin is disclosed in the U.S. Pat 5266319; The method of extracting corilagin from phyllanthus plant, Mang cattle Seedling platymiscium, Geranium plant is disclosed among the Chinese patent ZL97104154.7, and the activity of the anti-HBV of corilagin; The antithrombotic activity of corilagin is disclosed among the Chinese patent ZL00112894.9; Disclose corilagin among the Japan Patent JP2001072596 and can increase antibiotic antibacterial effect; The purposes of corilagin as antibacterial disclosed among the Japan Patent JP2004115453; People such as Liu Chaoyang have reported that corilagin has good inhibitory effect (referring to Liu Chaoyang etc. to Proliferation of Human Ovarian Cell, KB cell, people's human osteosarcoma cell, human colon cancer cell etc., the corilagin Antitumor Effects, treatment and prevention of tumour research, 2002,29 (5), 356-358).David E Berry etc. discloses activity (the David EBerry of corilagin as topoisomerase enzyme inhibitor adjusting DNA depolymerization, Naturally Occurring Inhibitors of Topoisomerase I Mediated DNARelaxation, J.Org.Chem.1992,57,420-422).
Yet, yet there are no the active report in corilagin gastric acid inhibitory secretion aspect so far, do not see the relevant report of the diseases such as hyperchlorhydria, peptic ulcer and chronic gastritis that corilagin treatment hyperchlorhydria is relevant yet.The inventor finds unexpectedly that through experimentation for many years corilagin has good restraining gastric acid secretion effect, also has better curative effect to the gastric ulcer experimental animal model, and finishes the present invention based on above discovery.
Summary of the invention
One aspect of the present invention provides corilagin or treatment of its officinal salt or the prevention hyperchlorhydria relevant disease purposes of formula I, and wherein said hyperchlorhydria relevant disease comprises hyperchlorhydria, peptic ulcer, chronic gastritis etc.; The relevant peptic ulcer of preferred hyperchlorhydria; The relevant gastric ulcer of hyperchlorhydria most preferably." hyperchlorhydria " of the present invention or " gastroxia " be meant cause or bring out human body pathological change or disease symptoms appear or cause the patient occur bad impression the gastric acid secretion amount relatively or too much absolute.Peptic ulcer of the present invention comprises gastric ulcer and duodenal ulcer.
Formula I
(chemical name: 1-O-Galla Turcica (Galla Helepensis) acyl-3,6-O-hexahydroxy biphenyl two formyls-β-D-glucose)
The present invention provides a kind of pharmaceutical composition for the treatment of the hyperchlorhydria relevant disease on the other hand, and it contains corilagin or its officinal salt, and one or more acceptable accessories.Described hyperchlorhydria relevant disease comprises hyperchlorhydria, peptic ulcer, chronic gastritis etc.; The relevant peptic ulcer of preferred hyperchlorhydria; The relevant gastric ulcer of hyperchlorhydria most preferably.
" officinal salt " of the present invention do not limit especially, can represent any medicinal salt that can be used in, for example front three amine salt, triethylamine salt, pyridiniujm, picolyl salt, hexanamine salt, N, N ,-dibenzyl ethylenediamine salt, N-methylglucosamine salt, diethanolamine salt, triethanolamine salt, three (hydroxyl methylamino) methane salt, phenethyl benzylamine salt etc.; Amino acid salts such as arginine salt, lysinate, serine salt, glycinate, aspartate, glutamate, Glu or alkali metal salt etc.
Corilagin provided by the invention can adopt disclosed method preparation among Chinese patent ZL97104154.7 or patent ZL00112894.9 or the patent ZL200510010880.1.
Corilagin of the present invention or its officinal salt are when the medicine of preparation treatment or prevention hyperchlorhydria relevant disease, can and mixing acceptable accessories, according to the pharmaceutical preparation technology of routine, be prepared into any pharmaceutical preparation of use clinically that is fit to.For example capsule, tablet, pill, granule, oral liquid etc.
Acceptable accessories comprises pharmaceutically acceptable filler, disintegrating agent, binding agent and lubricant, correctives etc.
Suitable filler such as lactose, microcrystalline Cellulose, pregelatinized Starch, starch, dextrin, mannitol, cellulose, sucrose, glucose, sorbitol, xylitol etc.
Suitable disintegrants such as polyvinylpolypyrrolidone, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, crosslinked hydroxypropyl emthylcellulose etc.
Suitable bonding such as polyvidone, hydroxypropyl cellulose, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, ethyl cellulose etc.
Examples of suitable lubricants such as micropowder silica gel, magnesium stearate, zinc stearate, calcium stearate, stearic acid, refining hydrogenated vegetable oil, Palmic acid, Pulvis Talci, Polyethylene Glycol, sodium lauryl sulphate, Stepanol MG etc.
Suitable correctives such as sucrose, simple syrup, glycerol, sorbitol, mannitol, stevioside, saccharin sodium etc.
The present invention collects 6 hours excretory gastric juice and estimates the influence of corilagin to gastric acid secretion by ligation rat pylorus, and result of the test shows that corilagin can effectively suppress the gastric acid secretion of rat, reduces gastric acidity.When the therapeutic effect of estimating peptic ulcer, adopt following three kinds of experimental animal models: pyloric ligation ulcers rat gastric ulcer model, water logging irritability rat gastric ulcer model, the acetic acid 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 gastric 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 gastric 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 irritability raise, and vasoconstriction causes the mucosa hypoxic-ischemic, and resistance descends.Parasympathetic nervous-hypophysis-adrenal system is excited to raise, and causes that gastric acid, pepsin and gastrin secretion increase, thereby causes stress ulcer.The acetic acid method is directly burnt the stomach serous coat with acetic acid 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: corilagin can significantly reduce gastric acid secretion, reduces ulcer incidence rate 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 acetic acid burn type gastric ulcer model had significant facilitation, and can increase the ulcer healing percentage rate, reduce ulcer index.Show that corilagin can be used in treatment or prevention gastroxia relevant disease.
Another aspect of the present invention is according to corilagin or the excretory effect of its officinal salt gastric acid inhibitory, and two class pharmaceutical compositions are provided.
One, based on corilagin or the effectively secretion of gastric acid inhibitory of its officinal salt, thereby reduce gastric acidity, improve gastric juice pH, with corilagin or its officinal salt and one or more under the gastric juice strong acid environment easily the destructive medicine of degraded carry out compatibility and form compositions, thereby reduce these medicines in the destructive situation of gastric, improve the absorption of medicine.This type of medicine comprises: omeprazole, Tenatoprazole, lansoprazole, pantoprazole, esomeprazole, rabeprazole, glycyrrhizic acid and all kinds of officinal salt thereof, Isoglycyrrhiza acid and all kinds of officinal salt thereof, erythromycin, midecamycin, josamycin etc.;
Two,, can have the gastrointestinal side effect compatibility of drugs with itself and one or more and form compositions, thereby reduce these medicines the gastrointestinal side effect according to corilagin or the excretory effect of its officinal salt gastric acid inhibitory.These medicines comprise: prednisone, dexamethasone, cortisone etc., aspirin, Phenylbutazone/crovaril, indometacin, ibuprofen, caffeine, reserpine, furosemide, acidum ethacrynicum, nicotinic acid, ferrous sulfate, ferrous fumarate, potassium chloride tablets, tolbutamide, chlortetracycline, 5-fluorouracil, cyclophosphamide, vinblastine, vincristine, colchicine, dactinomycin etc.
Pharmaceutical composition of the present invention can be corilagin or its officinal salt and one or more the said medicine pharmaceutical preparation technology according to routine, is prepared into any pharmaceutical preparation of use clinically that is fit to; Also can be to be prepared into suitable pharmaceutical preparation respectively to use simultaneously or substantially simultaneously.
Corilagin provided by the invention can significantly reduce gastric acid secretion, reduce gastric acidity, and can reduce the incidence rate and the ulcer index of ulcer, have the effect of good curing or prevention gastric ulcer, and can be prepared into pharmaceutical composition easily according to the conventional method of this area for clinical use.
The specific embodiment
Embodiment 1 corilagin is to the influence of rat tolerance secretion
1 material
1.1 reagent
Corilagin makes according to the method among the Chinese patent ZL97104154.7
Ranitidine hydrochloride is provided by Jiangxi Huiren Pharmaceutical Co., Ltd
Omeprazole is provided by AstraZeneca pharmaceutical Co. Ltd
Sodium carboxymethyl cellulose (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 centrifuge Beijing Medical Centrifugal Machine Factory
1.4 group and drug dose setting
Model group CMC-Na (0.5%)
Ranitidine group 100mg/kg
Omeprazole group 13.6mg/kg
Corilagin 40mg/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.
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, 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, 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. corilagin is to the excretory influence of pylorus ligation rat gastric juice (X ± SD)
Annotate: compare with the blank group,
*P＜0.05,
*P＜0.01.
4 conclusions
Corilagin can reduce rat total acidity gastric juice and total acid output, and the prompting corilagin has the excretory effect of gastric acid inhibitory.
Embodiment 2 corilagin anti-gastric-ulcer zooperies
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:
Corilagin: make according to the method among the Chinese patent ZL97104154.7
Positive drug: ranitidine hydrochloride capsules is provided by middle promise pharmaceutcal corporation, Ltd
Acetic acid: Shanghai is insulted wind chemical reagent company limited and is provided
Pentobarbital sodium: Chinese Medicine Shanghai chemical reagents corporation provides
1.3 equipment:
The rat fixing head, operating scissors, scalpel, tweezers, needle holder, microsyringe, balance
1.4 experiment condition:
The experimental rat sub-cage rearing, the feed full-valence pellet feed is freely drunk 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 group (135mg/kg), corilagin high dose group (40mg/kg), corilagin low dose group (20mg/kg).According to the continuous gastric infusion of 10ml/kg 5 days, the blank group gave the 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 pentobarbital sodium 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 normal 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 cardia 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 Mus number, ulcer number, ulcer level, ulcer area and pathological changes situation, calculate ulcer index with normal 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 gauges 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 gross 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 rate %=(blank group ulcer index-medication group ulcer index)/blank group ulcer index * 100%
The ulcer incidence rate: the number of animals that ulcer takes place accounts for the percentage ratio of laboratory animal number.
2.2 experimental result
To the influence of pyloric ligation ulcers gastric ulcer (X ± s)
| Group | Dosage mg/kg | Number of animals | Ulcer index | Ulcer suppresses percentage rate % | Ulcer incidence rate % | Gastric juice volume ml |
| Blank | - | 10 | 3.9±1.7 | 100 | 18.8±3.0 | |
| Ranitidine | 135 | 10 | 1.5±1.0 ** | 61.5 | 80 | 14.6±4.5 * |
| Corilagin | 40 | 10 | 1.3±1.6 ** | 66.7 | 60 | 12.0±5.4 ** |
| Corilagin | 20 | 10 | 3.0±1.7 | 23.1 | 100 | 13.8±6.4 * |
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 can reduce gastric acid secretion, reduces the incidence rate and the ulcer index of ulcer.The corilagin high and low dose can both reduce gastric acid secretion, reduces the incidence rate and the ulcer index of ulcer.Reduce gastric acid secretion during the corilagin high dose, effects such as the incidence rate of reduction ulcer and ulcer index are better than the ranitidine 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 group (135mg/kg), corilagin high dose group (40mg/kg), corilagin low dose group (20mg/kg).Rat was pressed the continuous gastric infusion of 10ml/kg 5 days, the blank group gives the equivalent distilled water, and last administration rat fasting in preceding 24 hours was fixed in the extremity 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 cardia and the pylorus stomach is taken out, inject 1% formalin 10ml to gastric, and stomach was immersed in 1% formalin 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 normal saline flush away gastric content.The degree of ulcer is represented with ulcer index, and the incidence rate of calculating ulcer inhibition percentage rate 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 rate %=(blank group ulcer index-medication group ulcer index)/blank group ulcer index * 100%
The ulcer incidence rate: the number of animals that ulcer takes place accounts for the percentage ratio 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 rate % | Ulcer incidence rate % |
| Blank | - | 10 | 11.9±5.4 | 0 | 100 |
| Ranitidine | 135 | 10 | 2.6±1.9 ** | 78.2 | 80 |
| Corilagin | 40 | 10 | 2.8±2.3 ** | 76.5 | 80 |
| Corilagin | 20 | 10 | 7.6±3.0 * | 36.1 | 100 |
Compare with the blank group
*Represent P＜0.05,
*Represent P＜0.01;
Experimental result shows: formed tangible gastric ulcer after the rat water logging in this experiment, shown the modeling success.Positive control medicine ranitidine has the obvious suppression effect to ulcer, and can significantly reduce ulcer index.Close during the corilagin high dose with the action effect of ranitidine, the ulcer of irritability rat gastric ulcer model is had inhibitory action, and dose-effect relationship is obvious, the high dose group effect is better than low dose group.
The 4 acetic acid 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 group (135mg/kg), corilagin high dose group (40mg/kg), corilagin low dose group (20mg/kg).The rat fasting after 24 hours, is carried out intraperitoneal injection of anesthesia with 5mg/100g body weight pentobarbital sodium, then its dorsal position is fixed on the operating-table.Cut the stomach wall hair, use the ethanol 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 acetic acid of 50 μ l10%, form pimple.Stomach is sent back to gently, sew up abdominal muscle, skin suture then.With iodine tincture, 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 the equivalent distilled water.Animal was all put to death in the 7th day.Open fu jie and prick pylorus and cardia, get stomach and be dipped in 1% formalin, fix 10 minutes.Cut off along greater gastric curvature, stomach is turned up, outwell content, reuse nipple suction pipe washes out food debris gently.Ulcer is rounded or oval, and central concave is swelled all around slightly, and blood capillary 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 rate, the evaluation medicine is to the facilitation of ulcer healing.
Ulcer healing percentage rate (%)=(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 gastric ulcer of rats acetic acid
| Group | Dosage mg/kg | Number of animals | Ulcer index mm | Ulcer healing percentage rate % |
| The blank group | - | 10 | 5.5±1.6 | |
| Ranitidine | 135 | 10 | 3.2±1.5 ** | 41.8 |
| Corilagin | 40 | 10 | 3.5±2.0 * | 36.4 |
| Corilagin | 20 | 10 | 4.2±1.7 | 23.6 |
Compare with the blank group
*Represent P＜0.05,
*Represent P＜0.01;
Healing to rat gastric ulcer during the corilagin high dose has significant facilitation, can increase the ulcer healing percentage rate, reduces ulcer index, and effects such as the incidence rate of reduction ulcer and ulcer index are all near with the ranitidine winding.Little during low dosage to the influence of ulcer healing and ulcer index.
Claims (8)
1. the corilagin of formula I or its officinal salt purposes in the medicine of preparation treatment or prevention hyperchlorhydria relevant disease.
2. the described purposes of claim 1, wherein the hyperchlorhydria relevant disease is hyperchlorhydria, peptic ulcer, chronic gastritis.
3. the described purposes of claim 1, wherein the hyperchlorhydria relevant disease is the relevant peptic ulcer of hyperchlorhydria.
4. the described purposes of claim 1, wherein the hyperchlorhydria relevant disease is the relevant gastric ulcer of hyperchlorhydria.
5. the purposes of a compositions that contains corilagin or its officinal salt and one or more acceptable accessories in the medicine of preparation treatment or prevention hyperchlorhydria relevant disease.
6. the described purposes of claim 5, wherein the hyperchlorhydria relevant disease is hyperchlorhydria, peptic ulcer, chronic gastritis etc.
7. the described purposes of claim 5, wherein the hyperchlorhydria relevant disease is the relevant peptic ulcer of hyperchlorhydria.
8. the described purposes of claim 5, wherein the hyperchlorhydria relevant disease is the relevant gastric ulcer of hyperchlorhydria.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101292872A CN101461816B (en) | 2007-12-21 | 2008-06-25 | Novel use of corilagin |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710192214 | 2007-12-21 | ||
| CN200710192214.3 | 2007-12-21 | ||
| CN2008101292872A CN101461816B (en) | 2007-12-21 | 2008-06-25 | Novel use of corilagin |
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| CN101461816A CN101461816A (en) | 2009-06-24 |
| CN101461816B true CN101461816B (en) | 2010-12-01 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2008101292853A Expired - Fee Related CN101461831B (en) | 2007-12-21 | 2008-06-25 | Geranium extract |
| CN2008101292872A Expired - Fee Related CN101461816B (en) | 2007-12-21 | 2008-06-25 | Novel use of corilagin |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2008101292853A Expired - Fee Related CN101461831B (en) | 2007-12-21 | 2008-06-25 | Geranium extract |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103749490B (en) * | 2014-01-08 | 2015-04-22 | 杨凌农科大无公害农药研究服务中心 | Plant virus resistant agent and preparation method thereof |
| 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 |
| CN113368119A (en) * | 2021-05-28 | 2021-09-10 | 昆明医科大学 | Application of Corilagin in preparation of medicine for treating burns and scalds |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1197641A (en) * | 1997-04-25 | 1998-11-04 | 中日友好临床医学研究所 | Medicine containing tan matter caesalpinia extract |
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| CN1857453B (en) * | 2006-03-03 | 2010-05-12 | 延边大学 | Chinese medicine composition for treating ulcerative colitis and its preparing method |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1197641A (en) * | 1997-04-25 | 1998-11-04 | 中日友好临床医学研究所 | Medicine containing tan matter caesalpinia extract |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101461831B (en) | 2011-07-20 |
| CN101461831A (en) | 2009-06-24 |
| CN101461816A (en) | 2009-06-24 |
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