CN105582017A - Composition for treating gastric ulcer combined gastrointestinal bleeding and preparation method of composition - Google Patents

Composition for treating gastric ulcer combined gastrointestinal bleeding and preparation method of composition Download PDF

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CN105582017A
CN105582017A CN201610097583.3A CN201610097583A CN105582017A CN 105582017 A CN105582017 A CN 105582017A CN 201610097583 A CN201610097583 A CN 201610097583A CN 105582017 A CN105582017 A CN 105582017A
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ginseng
ginsenoside
composition
pseudo
gastric ulcer
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CN105582017B (en
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谭喜梅
林艳英
邓裕彦
严灿梅
招丽君
杨北妮
黄源春
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Guangxi Wuzhou Pharmaceutical Group Co Ltd
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    • A61K31/7034Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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    • A61K9/1629Organic macromolecular compounds
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    • A61K2236/00Isolation 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
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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    • A61K2236/30Extraction of the material
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
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Abstract

The invention relates to a composition for treating a gastric ulcer combined gastrointestinal bleeding. The composition comprises the following active components in parts by weight: 8-25 parts of ginsenoside Re, 10-30 parts of ginsenoside Rg3 and 5-20 parts of ginsenoside Rh1. The composition has the effects of obviously improving the gastric mucosal lesion and gastric mucosal lesion, promoting the blood coagulation and stopping bleeding, and is capable of effectively treating and/or preventing gastrointestinal diseases of the gastric ulcer combined gastrointestinal bleeding and the like.

Description

A kind of composition and method of making the same for the treatment of gastric ulcer merging hemorrhage of gastrointestinal tract
Technical field
The present invention relates to field of medicaments, particularly a kind of composition and preparation thereof for the treatment of gastric ulcer merging hemorrhage of gastrointestinal tractMethod.
Background technology
In recent years, along with improving constantly of people's living standard, there is very large change in people's life style, followsAnd what come is that the incidence of disease and the illness rate of enterogastric diseases is all obvious ascendant trend. Gastric ulcer is in gastrointestinal system diseaseCommon disease, frequently-occurring disease, this disease is easy to merge and occurs gastrorrhagia, and main manifestations is stomachache, gasteremphraxis, suffers from diarrhoea, has blood in stool, vomits clinicallyThe symptoms such as blood, in traditional Chinese medicine, belong to the category such as " epigastric pain ", " ruffian is full ".
Aspect etiology and pathogenesis, the generation of the enterogastric diseases such as gastric ulcer, gastrorrhagia, think more main and weakness of the spleen and the stomach,The factors such as disorder of emotion, injury due to diet, being invaded by exogenous pathogen,invasion of exogenous pathogen are relevant, and wherein weakness of the spleen and the stomach is pathologic basis, the many simulataneous insufficiency and excessive of characteristic of disease. InMedical science is thought: overstrain, and injury due to diet, prolonged illness, plain body does not wait and all can undermine spleen sun, causes weakness of the spleen and the stomach.
Clinically, the enterogastric diseases such as gastric ulcer, gastrorrhagia that deficiency-cold in spleen and stomach is caused, doctor trained in Western medicine mainly adopts and presses down acid, onlyBitterly, the methods for the treatment of such as antidiarrheal, traditional Chinese medicine adopts warming stomach for dispelling cold, blood stasis removing analgesic, warming spleen and stopping diarrha method. Traditional Chinese medicine treatment at presentThis sick curative effect is proved, further adopts Chinese medicine extract to study, and more can give full play to the advantage of traditional Chinese medicine.
In recent years, the research of the each side such as extraction process, chemical composition and the pharmacological action of people to pseudo-ginseng is more and more.Modern study shows, the main chemical compositions of pseudo-ginseng comprises saponins, flavonoids, volatile oil, carbohydrate etc., and tcm clinical practice confirms threeSeven have loose stasis of blood hemostasis, the effect of detumescence ding-tong; Modern medicine study confirms that pseudo-ginseng has significantly and controls human body cardiovascular and cerebrovascular diseaseTreatment effect, have simultaneously hypoglycemic, anti-hypertension, antitumor, anticancer, protect the liver effects such as protecting kidney. Clinical pharmacology research shows, pseudo-ginsengWater extract-alcohol precipitation has certain protective effect to mucosal lesion; Saponin has good hemostasia effect, can be by carryingHigh platelet counts and ability of aggregation, shorten the hemorrhage and clotting time, reaches anastalsis.
CN1589808A " a kind of pharmaceutical composition and preparation technology and purposes for the treatment of peptic ulcer or enteritis ", itsActive principle is: herba fibraureae recisae alkaloid, arasaponin, bletilla polysaccharide, greater celandine alkaloid, its preparation method is: by every (orEvery of person, every ball) in contain in essence the herba fibraureae recisae alkaloid of 36-90mg, the arasaponin of 30-75mg, the bletilla of 30-75mgFour kinds of effective one-tenth of greater celandine alkaloid of polysaccharide, 0.5-2mg, mix rear pulverizing by these four kinds of effective ingredients preparations, cross 80~180 mesh sieves, reinstall capsule (soft, hard shell capsules for common drug) and make capsule (soft capsule, hard capsule), or further addAdd medicinal solvent or excipient, anticorrisive agent, adopt common pharmaceutical technology, make pill or granule, tablet. This patent is disclosedPurposes is the ulcer that treatment peptic ulcer class illness and helicobacter pylori cause, duodenal ulcer, and acute and chronic gastritis,Bacillary dysentery, enteritis, diarrhoea illness or be further used for preparation treatment peptic ulcer class medicine, but and not mentioned this medicine haveTreatment gastrorrhagia or treatment gastric ulcer merge the effect of gastrorrhagia.
Summary of the invention
The object of this invention is to provide a kind of composition that gastric ulcer merges hemorrhage of gastrointestinal tract for the treatment of;
The object of this invention is to provide a kind of preparation method that gastric ulcer merges the composition of hemorrhage of gastrointestinal tract that treats.
The object of the invention is to realize by following technical scheme:
Raw material sources of the present invention:
Pseudo-ginseng is dry root and the rhizome of Araliaceae Parmxnotoginseng (Burk.) F.H.Chen. Autumn, the flowers are in blossomBefore excavate, clean, separately main root, a root and rhizome, dry. Supporting root is practised and is claimed " rib ", and rhizome is practised title " clip ". [nature and flavor with returnThrough] sweet, micro-hardship, temperature. Return liver, stomach warp. [function with cure mainly] loose stasis of blood hemostasis, detumescence ding-tong. For spitting of blood, spit blood, Carp blood, justBlood, uterine bleeding, traumatism and bleeding, chest ventral spine pain, treating swelling and pain by traumatic injury.
The extracting method of inventor to ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1 in pseudo-ginseng of the present invention andIts curative effect has been carried out a large amount of systematic experimental studies, has finally obtained extractive technique scheme of the present invention, and the present invention adopts solelySpecial extract, purifying process resulting composition, its special character is, described composition is made up of the following composition of proportioning: ginsengSaponin(e Re:8~25 part, ginseng sapoglycoside Rg 3: 10~30 parts, ginsenoside Rh 1: 5~20 parts.
Preferably, arasaponin of the present invention, it is to be made up of the following composition of proportioning: ginsenoside Re: 15~25 parts, ginseng sapoglycoside Rg 3: 15~30 parts, ginsenoside Rh 1: 15~20 parts.
Preferably, arasaponin of the present invention, it is to be made up of the following composition of proportioning: ginsenoside Re: 25Part, ginseng sapoglycoside Rg 3: 25 parts, ginsenoside Rh 1: 15 parts.
The invention also discloses and there is the method that treatment gastric ulcer merges the composition of hemorrhage of gastrointestinal tract effect a kind of preparation, concreteStep is as follows:
(1) Radix Notoginseng powder is broken into 40 order meal, adding 20 times of percents by volume of medicinal material weight is that 70-80% alcohol reflux extracts 2~3Inferior, each 1~3h, filters, and merging filtrate, obtains pseudo-ginseng alcohol extract; The dregs of a decoction add 10-15 times of water refluxing extraction 2 of medicinal material weight againInferior, each 1~2h, filters, and merging filtrate, obtains pseudo-ginseng water extract; Merge pseudo-ginseng alcohol extract and water extraction liquid, concentrated, dry, obtain threeSeven dry extracts; Pseudo-ginseng dry extract, adds a small amount of ethanol to dissolve, by D101 macroporous adsorbent resin column chromatography, first with 1-4BV go fromSub-water elution, discards eluent; Be 70-80% ethanol elution by 2-6BV percent by volume again, elution speed is 1~3BV/H, merges ethanol eluate, reclaims solvent, dry, obtains arasaponin;
(2), after arasaponin is dissolved in water, upper HPD-100 resin column, with 1~4BV deionized water wash-out, discards eluent;With 1~3BV15% ethanolic solution wash-out, discard eluent; Use successively 2~5BV30%, 2~5BV50%, 2~4BV75%Ethanol elution, elution speed is 2~5BV/h, collects respectively each section of eluent, obtains ginsenoside Re, ginseng sapoglycoside Rg 3, ginsengThe eluent of saponin(e Rh1, reduced pressure concentration, dry;
(3), by ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1 mix by weight portion described in claim 1, to obtain final product.
Preferably, preparation method is:
(1) Radix Notoginseng powder is broken into 40 order meal, adding 20 times of percents by volume of medicinal material weight is that 75% alcohol reflux extracts 2 times, each3h, filters, and merging filtrate, obtains pseudo-ginseng alcohol extract; The dregs of a decoction add 12 times of water refluxing extraction of medicinal material weight 2 times again, each 1.5h, mistakeFilter, merging filtrate, obtains pseudo-ginseng water extract; Merge pseudo-ginseng alcohol extract and water extraction liquid, 80 DEG C of reduced pressure concentrations, dry, obtain that pseudo-ginseng is dry to be soakedCream; Pseudo-ginseng dry extract, adds a small amount of 70% ethanol to dissolve, and by D101 macroporous adsorbent resin column chromatography, first uses 2BV deionized waterWash-out, discards eluent; Be 75% ethanol elution by 4BV percent by volume again, elution speed is 3BV/h, merges ethanol and washesDe-liquid, reclaims solvent, and 80 DEG C dry, obtains arasaponin;
(2), after arasaponin is dissolved in water, upper HPD-100 resin column, with 2BV deionized water wash-out, discards eluent; With2BV15% ethanolic solution wash-out, discards eluent; Use successively 4BV30%, 4BV50%, 3BV75% ethanol elution, wash-out speedDegree, for 3BV/h, is collected respectively each section of eluent, obtains the eluent of ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1, subtractsPress and concentrate, 65 DEG C dry;
(3), by ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1 mix by weight portion described in claim 1, to obtain final product.
The present invention also provides the pharmaceutical preparation containing above-mentioned composition, and said preparation was by above-mentioned composition and pharmaceutically acceptable yearBody composition.
Described preparation is solid pharmaceutical preparation or liquid preparation, and solid pharmaceutical preparation is tablet, capsule or granule; Liquid preparation isMixture or oral liquid.
Described pharmaceutically acceptable carrier is lactose, starch, dextrin, sweet mellow wine, sucrose, HPMC, friendshipConnection sodium carboxymethylcellulose, low-substituted hydroxypropyl cellulose, microcrystalline cellulose, superfine silica gel powder, pregelatinized starch, sorbierite, hardFatty acid magnesium, talcum powder, HPMC, low-substituted hydroxypropyl cellulose, Sodium Benzoate, potassium sorbate, sucrose or A SiOne or more of Ba Tianzhong, monosodium glutamate, honey, orange flavor.
The preparation method of arasaponin pharmaceutical preparation of the present invention, the method can adopt the preparation of conventional formulation techniqueFor various common formulations.
The present invention also provides above-mentioned composition or preparation to merge the enterogastric diseases such as gastrorrhagia in preparation treatment gastric ulcerThe application of Shi Tigao result for the treatment of.
Inventor finds in research gastric ulcer merges the therapeutic process of hemorrhage of gastrointestinal tract, and panax araliaceae plant has goodGood protection stomach lining, the effect of promotion blood coagulation hemostasis. Notogineng Extract and arasaponin can significantly reduce the stomach of rat and burstUlcer index, the platelet count of increase rat, the prothrombin time of shortening rat, and bad reaction is few. The present invention studies cardThe intestines and stomach microcirculation that has clear improvement of real pseudo-ginseng, Notogineng Extract and arasaponin tool, the effect of protection mucosal lesion, canBe used for the treatment of the enterogastric diseases such as gastric ulcer, hemorrhage of gastrointestinal tract that deficiency-cold in spleen and stomach causes, and there is determined curative effect, safety, useEasy, the feature such as bad reaction is few. Also not exclusively clear to its concrete mechanism of action at present, but arasaponin closes gastric ulcerAnd gastrorrhagia animal model has good the protective effects on gastric mucosa and blood coagulation anastalsis, point out it to there is good treatment stomachUlcer and gastrorrhagia effect.
Therefore, applicant puies forward the group of pseudo-ginseng activity component extract ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1Compound is enough in the new purposes that treatment gastric ulcer merges gastrorrhagia medicine aspect.
The new purposes that composition provided by the invention merges gastrorrhagia medicine aspect for gastric ulcer has the following advantages:
1, the each composition of the present composition extracts and obtains from panax araliaceae plant, and safety non-toxic, can long-term taking.
2, experimental result shows, the gastric ulcer that said composition can significantly reduce gastric ulcer merging gastrorrhagia animal model refers toCount, significantly shorten bleeding time and the clotting time of rat.
Detailed description of the invention
Further illustrate the present invention below by embodiment. It should be understood that embodiments of the invention are for explanationThe present invention instead of limitation of the present invention. The simple modifications that essence according to the present invention is carried out the present invention all belongs to the present inventionClaimed scope. Except as otherwise noted, the percentage of the amount of alcohol in the present invention is percentage by volume, and v/v represents solutionVolume ratio.
Embodiment 1: the preparation of composition of the present invention
(1) take pseudo-ginseng 2kg, be ground into 40 order meal, add 20 times of 75% alcohol reflux of medicinal material weight to extract 2 times, each 3h,Filter, merging filtrate, obtains pseudo-ginseng alcohol extract; The dregs of a decoction add 12 times of water refluxing extraction of medicinal material weight 2 times again, and each 1.5h, filters,Merging filtrate, obtains pseudo-ginseng water extract; Merge pseudo-ginseng alcohol extract and water extraction liquid, 80 DEG C of reduced pressure concentrations, dry, obtain pseudo-ginseng dry extract;Pseudo-ginseng dry extract, adds a small amount of 70% ethanol to dissolve, by D101 macroporous adsorbent resin column chromatography, first with the washing of 2BV deionizationDe-, discard eluent; Use 4BV75% ethanol elution, elution speed is 3BV/h again, merges ethanol eluate, reclaims solvent,80 DEG C dry, obtains arasaponin;
(2), after arasaponin is dissolved in water, upper HPD-100 macroreticular resin, with 2BV deionized water wash-out, discards eluent; With2BV15% ethanolic solution wash-out, discards eluent; Use successively 4BV30%, 4BV50%, 3BV75% ethanol elution, wash-out speedDegree, for 3BV/h, is collected respectively each section of eluent, obtains the eluent of ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1, subtractsPress and concentrate, 65 DEG C dry, obtains ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1;
(3) by ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1 mix by following weight portion: 25g, 25g, 15g mix,Obtain.
Embodiment 2: the preparation of composition of the present invention
(1) take pseudo-ginseng 2kg, be ground into 40 order meal, add 15 times of 70% alcohol reflux of medicinal material weight to extract 2 times, each 1h,Filter, merging filtrate, obtains pseudo-ginseng alcohol extract; The dregs of a decoction add 10 times of water refluxing extraction of medicinal material weight 2 times again, and each 1h, filters, and closesAnd filtrate, obtain pseudo-ginseng water extract; Merge pseudo-ginseng alcohol extract and water extraction liquid, 80 DEG C of reduced pressure concentrations, dry, obtain pseudo-ginseng dry extract; ThreeSeven dry extracts, add a small amount of 70% ethanol to dissolve, and by D101 macroporous adsorbent resin column chromatography, first use 1BV deionized water wash-out,Discard eluent; Use 2BV70% ethanol elution, elution speed is 1BV/h again, merges ethanol eluate, reclaims solvent, 80 DEG CDry, obtain arasaponin;
(2), after arasaponin is dissolved in water, upper HPD-100 macroreticular resin, with 1BV deionized water wash-out, discards eluent; With1BV15% ethanolic solution wash-out, discards eluent; Use successively 2BV30%, 2BV50%, 2BV75% ethanol elution, wash-out speedDegree, for 2BV/h, is collected respectively each section of eluent, obtains the eluent of ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1, subtractsPress and concentrate, 65 DEG C dry, obtains ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1;
(3) by ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1 mix by following weight portion: 8g, 10g, 5g mix,.
Embodiment 3: the preparation of composition of the present invention
(1) take pseudo-ginseng 2kg, be ground into 40 order meal, add 25 times of 70% alcohol reflux of medicinal material weight to extract 3 times, each 3h,Filter, merging filtrate, obtains pseudo-ginseng alcohol extract; The dregs of a decoction add 15 times of water refluxing extraction of medicinal material weight 2 times again, and each 2h, filters, and closesAnd filtrate, obtain pseudo-ginseng water extract; Merge pseudo-ginseng alcohol extract and water extraction liquid, 80 DEG C of reduced pressure concentrations, dry, obtain pseudo-ginseng dry extract; ThreeSeven dry extracts, add a small amount of 70% ethanol to dissolve, and by D101 macroporous adsorbent resin column chromatography, first use 4BV deionized water wash-out,Discard eluent; Use 3BV70% ethanol elution, elution speed is 1BV/h again, merges ethanol eluate, reclaims solvent, 80 DEG CDry, obtain arasaponin;
(2), after arasaponin is dissolved in water, upper HPD-100 macroreticular resin, with 4BV deionized water wash-out, discards eluent; With3BV15% ethanolic solution wash-out, discards eluent; Use successively 5BV30%, 5BV50%, 4BV75% ethanol elution, wash-out speedDegree, for 5BV/h, is collected respectively each section of eluent, obtains the eluent of ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1, subtractsPress and concentrate, 65 DEG C dry, obtains ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1;
(3) by ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1 mix by following weight portion: 25g, 30g, 20g mix,Obtain.
Embodiment 4: the preparation of composition of the present invention
Get embodiment 1 step (2) gained ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1, mix by following weight portion:15g, 15g, 15g mix, and to obtain final product.
Embodiment 5: the preparation of composition of the present invention
Get embodiment 2 steps (2) gained ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1, mix by following weight portion:25g, 30g, 20g mix, and to obtain final product.
Embodiment 6: granule of the present invention
Get embodiment 1 resulting composition, add supplementary product starch, sucrose, lactose to mix, with 70% ethanol softwood processed, cross 60 ordersSieve series grain, dry, whole grain, packing, granulation agent, to obtain final product.
Embodiment 7: tablet of the present invention
Get embodiment 2 resulting compositions, add microcrystalline cellulose excipients, hydroxypropyl cellulose, sodium carboxymethyl starch to mix,Add lubricant talcum powder, dolomol to mix, compressing tablet, to obtain final product.
Embodiment 8: capsule of the present invention
Get embodiment 3 resulting compositions, be dried to dried cream powder, after adding the conventional auxiliary material of the capsules such as starch lactose to mix,Production method preparation routinely, pulverizes, sieves, and filling, fit, to obtain final product.
Comparative example 1:
Take pseudo-ginseng 2kg, be ground into 40 order meal, add 20 times of 75% alcohol reflux to extract 2 times, each 3h, filters, and merges filterLiquid, obtains pseudo-ginseng alcohol extract; The dregs of a decoction add 12 times of water refluxing extraction 2 times again, and each 1.5h, filters, and merging filtrate, obtains pseudo-ginseng water extractionLiquid; Merge pseudo-ginseng alcohol extract and water extraction liquid, 80 DEG C of reduced pressure concentrations, dry, obtain pseudo-ginseng dry extract; Pseudo-ginseng dry extract, adds a small amount of70% ethanol dissolves, and by D101 macroporous adsorbent resin column chromatography, first uses 2BV deionized water wash-out, discards eluent; Use again4BV75% ethanol elution, elution speed is 3BV/h, merges ethanol eluate, reclaims solvent, 80 DEG C are dry, obtain pseudo-ginseng totalSaponin(e, adds starch, granulates, and reinstalls capsule, makes capsule.
Pharmacodynamics test:
1 experiment material
1.1 animal used as test
SPF level SD rat, male, 180~220 grams, 10 every group. Buy from Guangxi Medical University's Experimental Animal Center licenseCard SCXK(Hunan) 2015-0003.
1.2 given the test agent and reagent
Embodiment 1, comparative example 1 medicine; Aspirin (Changbaishan Pharmacy Co., Ltd, lot number: 140101); Chloraldurate(Chengdu Ke Long chemical reagent factory, lot number: 2013092101); Formaldehyde (Bo Di chemical inc, Tianjin, lot number:20140401)。
1.3 laboratory apparatus
Anatomical lens with scale, the long ELIASA of EPOCHBIOTEK all-wave (Bai Teng Instrument Ltd. of the U.S.).
2 experimental techniques
2.1 gastric ulcer merge the modeling of gastrorrhagia rat animal model
Get at random 10 as blank group, all the other rat fasting be can't help water after 18 hours, with etherization, were fixed on plankUpper, is immersed in the Water Tank with Temp.-controlled of 23 DEG C, water is in the 30min of xiphoid-process portion, the aspirin that while gavage dosage is 6mg/kg,Dosage is 10ml/kg, every day gavage 2 times, continuously gavage 7 days, preparation gastric ulcer merges gastrorrhagia rat model.
2.2 animal grouping and administrations
After modeling, be divided at random 1 group of model group, positive group and embodiment by body weight. Positive group gives the Aomei that dosage is 4mg/kgDraw azoles, each administration gives corresponding embodiment medicine, and dosage is 20ml/kg, administration every day 1 time, continuous 30 days, blank group andThe isopyknic distilled water of model group gavage.
2.3 collections of specimens and detection
After last administration, fasting be can't help water after 12 hours, from rat tail vein blood sampling, measured platelet counts (/L) and fibrin fermentThe former time (PT). Then use chloral hydrate anesthesia rat, cut abdominal cavity open, ligation pylorus and orifice of the stomach, take out whole stomach, intragastric infusion10% formalin of 5mL, soaks and cuts off along greater curvature after 10 minutes, cleans content, and whole stomach is launched to be laid in glass plateUpper, paper using blots the moisture in ulcer, and a situation arises to observe gastric ulcer, and ulcer level is evaluated, to ulcer levelAssessment method be: by ulcer area and quantity in conjunction with dividing UI, 0: without ulcer; 1:1~3 aphtha (3mm withUnder); 2:3 above aphtha or 1 large ulcer; 3:1 large ulcer and several aphtha; 4: several large ulcer; 5: pierceabilityUlcer; Calculate ulcer inhibition percentage: ulcer inhibition percentage=(model control group UI-administration group UI)/Model control group UI/100%.
3 statistical procedures
Experimental data adopt SPSS carry out statistical procedures, continuous data with± s represents, relatively adopts two sample averages between groupT inspection, between many groups, sample average relatively adopts variance analysis; Think there is significant difference with P < 0.05.
4 experimental results
4.1 impacts on rat gastric ulcer index, experimental result is in table 1
The impact of each group of table 1 on rat ulcer index (±s,n=10)
Group Dosage (mg/kg) UI Inhibiting rate (%)
Blank group / 0.90±0.85 /
Model group / 4.52±0.76** /
Omeprazole group 4 2.64±0.82△△ 41.59%
1 group of embodiment 22.5 2.58±0.84△△## 42.92%
4 groups of embodiment 22.5 2.61±1.02△△## 41.25%
1 group of comparative example 48 3.20±0.75△ 35.86%
Note: with the comparison of blank group, * * p < 0.01, * p < 0.05; With model group comparison, △ △ P < 0.01, △ P <0.05;##p<0.01,#p<0.05。
4.2 impacts on rat platelet counting (/L) and prothrombin time (PT), experimental result is in table 2
The impact of table 2 on rat platelet counting and prothrombin time
Group Dosage (mg/kg) Platelet count (109/L) PT(s)
Blank group 470.29±45.84 10.56±3.58
Model group 379.56±30.72** 18.27±3.71**
Omeprazole group 4 453.88±42.63△△ 12.86±4.32△△
1 group of embodiment 22.5 449.05±38.67△△## 13.45±5.26△
4 groups of embodiment 22.5 451.37±36.28△△## 12.92±5.31△△
1 group of comparative example 48 419.75±30.58△ 15.83±4.65
Note: with the comparison of blank group, * * p < 0.01, * p < 0.05; With model group comparison, △ △ P < 0.01, △ P <0.05;##p<0.01,#p<0.05。
Conclusion: experimental result demonstration, model group rat platelet counting is obviously less than blank group, and ulcer indexWith the clotting time more than Normal group. Each administration group platelet count is apparently higher than model group, when ulcer index and blood coagulationBetween all lower than model group, with comparative example comparison, each embodiment group platelet count is apparently higher than comparative example group, ulcer index andClotting time, between above group, index comparing difference all had significant difference (P < 0.05 or P < 0.01) all lower than comparative example group. SayThe bright present composition has good protection stomach lining, promotes the effect of blood coagulation hemostasis, can effectively treat gastric ulcer and mergeThe enterogastric diseases such as gastrorrhagia, and result for the treatment of is obviously better than prior art.
Although, above use general explanation, detailed description of the invention and test, the present invention has been done to detailed retouchingState, but on basis of the present invention, can make some modifications or improvements it, this is apparent to those skilled in the art. Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the present invention claimedScope.

Claims (8)

1. a composition for the treatment of gastric ulcer merging hemorrhage of gastrointestinal tract, is characterized in that, described composition is by following weight portionOne-tenth be grouped into:
Ginsenoside Re: 8~25 parts, ginseng sapoglycoside Rg 3: 10~30 parts, ginsenoside Rh 1: 5~20 parts.
2. treatment gastric ulcer according to claim 1 merges the composition of hemorrhage of gastrointestinal tract, it is characterized in that described combinationThing is grouped into by the one-tenth of following weight portion:
Ginsenoside Re: 15~25 parts, ginseng sapoglycoside Rg 3: 15~30 parts, ginsenoside Rh 1: 15~20 parts.
3. treatment gastric ulcer according to claim 2 merges the composition of hemorrhage of gastrointestinal tract, it is characterized in that described combinationThing is made up of the following composition of weight portion proportioning: ginsenoside Re: 25 parts, ginseng sapoglycoside Rg 3: 25 parts, ginsenoside Rh 1: 15Part.
4. treatment gastric ulcer according to claim 2 merges the composition of hemorrhage of gastrointestinal tract, it is characterized in that preparation methodComprise the steps:
(1) Radix Notoginseng powder is broken into meal, adding percent by volume is that 70-80% alcohol reflux extracts 2~3 times, each 1~3h, mistakeFilter, merging filtrate, obtains pseudo-ginseng alcohol extract; The dregs of a decoction add 10-15 times of water refluxing extraction of medicinal material weight 2 times again, each 1~2h, mistakeFilter, merging filtrate, obtains pseudo-ginseng water extract; Merge pseudo-ginseng alcohol extract and water extraction liquid, concentrated, dry, obtain pseudo-ginseng dry extract; Pseudo-ginseng is dryMedicinal extract, adds a small amount of ethanol to dissolve, and by D101 macroporous adsorbent resin column chromatography, first uses 1-4BV deionized water wash-out, discards and washesDe-liquid; Be 70-80% ethanol elution by 2-6BV percent by volume again, elution speed is 1~3BV/h, merges ethanol elutionLiquid, reclaims solvent, dry, obtains arasaponin;
(2), after arasaponin is dissolved in water, upper HPD-100 resin column, with 1~4BV deionized water wash-out, discards eluent;With 1~3BV15% ethanolic solution wash-out, discard eluent; Use successively 2~5BV30%, 2~5BV50%, 2~4BV75%Ethanol elution, elution speed is 2~5BV/h, collects respectively each section of eluent, obtains ginsenoside Re, ginseng sapoglycoside Rg 3, ginsengThe eluent of saponin(e Rh1, reduced pressure concentration, dry;
(3), by ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1 mix by weight portion described in claim 1, to obtain final product.
5. treatment gastric ulcer according to claim 4 merges the composition of hemorrhage of gastrointestinal tract, it is characterized in that preparation methodComprise the steps:
(1) Radix Notoginseng powder is broken into 40 order meal, adding 20 times of percents by volume of medicinal material weight is that 75% alcohol reflux extracts 2 times, each3h, filters, and merging filtrate, obtains pseudo-ginseng alcohol extract; The dregs of a decoction add 12 times of water refluxing extraction of medicinal material weight 2 times again, each 1.5h, mistakeFilter, merging filtrate, obtains pseudo-ginseng water extract; Merge pseudo-ginseng alcohol extract and water extraction liquid, 80 DEG C of reduced pressure concentrations, dry, obtain that pseudo-ginseng is dry to be soakedCream; Pseudo-ginseng dry extract, adds a small amount of 70% ethanol to dissolve, and by D101 macroporous adsorbent resin column chromatography, first uses 2BV deionized waterWash-out, discards eluent; Be 75% ethanol elution by 4BV percent by volume again, elution speed is 3BV/h, merges ethanol and washesDe-liquid, reclaims solvent, and 80 DEG C dry, obtains arasaponin;
(2), after arasaponin is dissolved in water, upper HPD-100 resin column, with 2BV deionized water wash-out, discards eluent; With2BV15% ethanolic solution wash-out, discards eluent; Use successively 4BV30%, 4BV50%, 3BV75% ethanol elution, wash-out speedDegree, for 3BV/h, is collected respectively each section of eluent, obtains the eluent of ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1, subtractsPress and concentrate, 65 DEG C dry;
(3), by ginsenoside Re, ginseng sapoglycoside Rg 3, ginsenoside Rh 1 mix by weight portion described in claim 1, to obtain final product.
6. treat a preparation for gastric ulcer merging hemorrhage of gastrointestinal tract, by the treatment gastric ulcer described in claims 1 to 3 any oneThe composition that merges hemorrhage of gastrointestinal tract can prepare and form with the carrier of pharmaceutically accepting.
7. treatment gastric ulcer according to claim 6 merges the preparation of hemorrhage of gastrointestinal tract, it is characterized in that described medicine and pharmacologyThe carrier of upper acceptance comprises: lactose, starch, dextrin, sweet mellow wine, sucrose, HPMC, cross-linked carboxymethyl celluloseSodium, low-substituted hydroxypropyl cellulose, microcrystalline cellulose, superfine silica gel powder, pregelatinized starch, sorbierite, dolomol, talcum powder,In HPMC, low-substituted hydroxypropyl cellulose, Sodium Benzoate, potassium sorbate, sucrose or Aspartame, monosodium glutamate, honeybeeThe mixing of any one or more in honey, orange flavor.
8. treatment gastric ulcer according to claim 6 merges the preparation of hemorrhage of gastrointestinal tract, it is characterized in that described medicine systemAgent comprises capsule, tablet, granule, mixture, oral liquid, syrup etc.
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