CN1457829A - Chinese medicine composition for curing chronic atrophic sastritis and its preparing method and quality control method - Google Patents
Chinese medicine composition for curing chronic atrophic sastritis and its preparing method and quality control method Download PDFInfo
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- CN1457829A CN1457829A CN03121887A CN03121887A CN1457829A CN 1457829 A CN1457829 A CN 1457829A CN 03121887 A CN03121887 A CN 03121887A CN 03121887 A CN03121887 A CN 03121887A CN 1457829 A CN1457829 A CN 1457829A
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Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The Chinese medicine composition is prepared with lily, Tuckahoe, figwort, Chuanxiong rhizome, chicken's gizzard membrane and other 13 kinds of Chinese medicinal materials. During its preparation, the materials are water decocted and alcohol deposited to extract the effective components. Meanwhile, component identification and content measurement method are provided to control the quality of the medicine product. The Chinese medicine composition has excellent curative effect on chronic atrophic gastritis and no toxic side effect.
Description
Invention field
The present invention relates to a kind of Chinese medicine composition, particularly be used for the treatment of the Chinese medicine composition of chronic atrophic gastritis, relate to the preparation method and the method for quality control of said composition simultaneously.
Background technology
Chronic atrophic gastritis is a kind of commonly encountered diseases, because atrophic gastritis is the cercinoma prophase pathologic change of gastric cancer or to be considered to may be the latency of gastric cancer, therefore, primary disease has caused the extensive attention of medical circle at home and abroad, and the medicine of development treatment atrophic gastritis not only has clinical value but also also seems very important to preventing and treating gastric cancer the radical cure primary disease.At present atrophic gastritis still there is not satisfied medicine.
Summary of the invention
One object of the present invention is to disclose a kind of Chinese medicine composition of new treatment chronic atrophic gastritis; Another object of the present invention is the method for a kind of new treatment chronic atrophic gastritis Chinese medicine composition of open preparation; The object of the invention also is to disclose a kind of method of quality control of new Chinese medicine composition.
Pharmaceutical composition of the present invention is made up of following raw material medicaments, each crude drug component and proportioning following (by weight):
Bulbus Lilii 50-70 weight portion Poria 50-70 weight portion Radix Scrophulariae 60-90 weight portion
Rhizoma Chuanxiong 30-50 weight portion Endothelium Corneum Gigeriae Galli 10-20 weight portion Radix Linderae 30-50 weight portion
Rhizoma Alismatis 30-50 weight portion 60-90 Radix Ophiopogonis weight portion Radix Notoginseng 10-20 weight portion
Rhizoma Atractylodis Macrocephalae 20-40 weight portion Radix Angelicae Sinensis 30-50 weight portion Herba Artemisiae Scopariae 50-70 weight portion
Radix Sanguisorbae 60-90 weight portion Pollen Typhae 30-50 weight portion Rhizoma Corydalis 50-70 weight portion
Radix Paeoniae Alba 130-170 weight portion Herba Dendrobii 60-90 weight portion Rhizoma Anemones Altaicae 30-50 weight portion.
Described Rhizoma Atractylodis Macrocephalae parched with bran, the Rhizoma Corydalis processed with vinegar, Endothelium Corneum Gigeriae Galli is selected Endothelium Corneum Gigeriae Galli (parched) for use.
This preparation of drug combination method:
More than 18 flavors, decoct with water 1.5-3 hour at every turn 1-3 time, collecting decoction filters, and filtrate is concentrated in right amount, add ethanol, make to contain the alcohol amount and reach 60-80%, leave standstill, filter, reclaim ethanol, filtrate concentrates, adding water-cooled hides, filter, at last directly or add pharmaceutically acceptable excipient and make clinical acceptable forms through conventional operation, as tablet, capsule, pill, granule, suspensoid, drop pill, oral liquid etc.The method of quality control of this composition oral liquid formulation comprises to be differentiated and/or assay.
Discrimination method comprises a kind of and/or several in the following method:
A. get this product 20ml,, extract 2 times with the ether jolting to 2-3 with hydrochloric acid adjusting pH value, each 25ml merges ether solution, and evaporate to dryness, residue add methanol 1ml makes dissolving, as supplying the brilliant solution of examination; Other gets and does not eat in acid contrast crystalline substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 2～5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel C lamellae of adhesive with the sodium carboxymethyl cellulose, with 5-7: 2-4: 1-2 toluene-ethyl acetate-formic acid is developing solvent, launch, take out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
B. get this product 30ml, add the chloroform jolting and extract 2 times, each 20ml, combined chloroform liquid, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Herba Artemisiae Scopariae control medicinal material 2g, adds water 60ml, and reflux 25-35 minute, put coldly, filter, add chloroform and shine medical material solution in pairs with legal system; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 5-10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the Sodium Tvlose, with 1-3: 0.5-1.5 petroleum ether (30-60 ℃)-ethyl acetate is developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution-alcoholic solution of new preparation 0.5-1.5: 2-5, and it is clear to be heated to the speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
C. get this product 20ml, add n-butyl alcohol 25ml, jolting is extracted, and divide and get n-butyl alcohol liquid, evaporate to dryness, residue dissolves with small amount of methanol, by the neutral alumina post, with methanol 20ml eluting, collects eluent, and evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material 2g, adds water 30ml, decocts 25-35 minute, filters, and filtrate adds n-butyl alcohol 25ml, and jolting is extracted, and divides and gets n-butyl alcohol liquid, and evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution; Get the peoniflorin reference substance again, add methanol and become every 1ml to contain the solution of 1mg, product solution in contrast; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 3～8 μ l of above-mentioned three kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 4-6: 2-5: 1-2: 0.5-1.5 ethyl acetate-butanone-formic acid-water is developing solvent, launches, and takes out, dry, spray is with 5% vanillin sulfuric acid solution-alcoholic acid mixed solution, and vanillin sulfuric acid solution-alcoholic acid ratio is 1-3: 7-9, and it is clear to be heated to speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show an identical punctation: with the corresponding position of reference substance on, show identical blue spot;
Assay is measured according to high-efficient liquid phase technique (appendix VID of Chinese Pharmacopoeia version in 2000), chromatographic condition and system suitability test, and be filler: 16-25 with octadecylsilane chemically bonded silica: 70-85 second eyeball-0.1% phosphoric acid solution is a mobile phase; The detection wavelength is 230nm; Number of theoretical plate calculates by the peoniflorin peak should be not less than 1500; The preparation of reference substance solution, the peoniflorin reference substance is an amount of, and accurate the title, decide, and adds 45-55% methanol and make the solution that every 1ml contains 0.1mg, promptly; The preparation of need testing solution: this product under the loading amount item, mixing, precision is measured 10ml, puts in the separatory funnel, add water 10ml, shake up, extract 5 times with water saturated n-butyl alcohol jolting, merge n-butyl alcohol liquid, evaporate to dryness, residue add 45-55% methanol makes dissolving, move in the 25ml measuring bottle, and be diluted to scale, shake up, precision is measured 5ml, puts in the 25ml measuring bottle, adds 45-55% methanol and is diluted to scale, shake up, filter, promptly; Algoscopy: the accurate respectively brilliant solution of contrast and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; Present composition oral liquid formulations per unit amount contains the Radix Paeoniae Alba in peoniflorin (C
23H
28O
11) meter, must not be less than 5.0mg.
Described unit quantity is the pharmaceutical quantities of suitable crude drug amount 10.2g.
The present composition all has obvious effects at treatment atrophic gastritis and other gastropathy, and the toxicity that has no adverse reaction is very little, and clinical practice is safe and reliable.
Following experimental example is used to further specify the present invention.
The used MOLUO DAN of following experimental example, sieve that rubs drink are respectively the pill and the oral liquid of the present composition.
Experimental example 1Sieve that rubs drink is to the influence of rat experiment chronic gastritis.Experiment material: (1) laboratory animal: healthy Wistar rat, body weight 216.45 ± 31.27g.Animal housing provides with the institute for drug control, Tianjin.(2) experimental drug: sieve that rubs drink, MOLUO DAN.Provide by Handan Pharmaceutical Co., Ltd.Experimental technique
One, the equipment of experimental chronic gastritis animal model
Get the gastric mucosa of Wistar rat, be prepared into the normal saline homogenate, be made into Emulsion with 1: 1 ratio with complete freund adjuvant.Subcutaneous injection 0.5ml carries out immunity, and every 14 days, again with the same dose subcutaneous injection once, the promptly severe gastric mucosa generation cellular infiltration that brings out formed experimental chronic gastritis animal model after 30 days.
Two, the preparation of freund adjuvant fully
(1) anhydrous lanolin and white oil be mixed in proportion be prepared into the thickness emulsus,
(2) with itself and used equipment autoclaving,
(3) under aseptic technique, add the bacillus calmette-guerin vaccine of deactivation, be placed on and change the refrigerator preservation in the pearl bottle of no cingula over to.
Three, experiment grouping and step
Get 64 of healthy Wistar rats, male and female half and half are divided into 6 groups at random.1 prevention matched group gives normal saline (0.7ml/100g) and irritated stomach 14 days, forms the chronic gastritis animal model then.2 prevention groups, sieve that rubs drink (0.7ml/100g), once a day.After 14 days, finish the process that forms the chronic gastritis animal model again, 3 treatment matched groups after forming the chronic gastritis animal model, are irritated stomach with normal saline (1.5ml/ only).4.5 and 6 groups after forming animal model, treats with rub sieve drink heavy dose of (7.00g/kg) and low dose (3.50g/kg) and MOLUO DAN (0.45g/kg) respectively.Began 7 days, be administered twice every day, changes into once a day later on.Be divided into and treat 14 days and 23 days two courses of treatment, every treated animal is all weighed before and after experiment, and the record ordinary circumstance.After experiment finished, fasting be can't help water and was adopted the vertebra dislocation method to put to death animal in 24 hours, takes out full stomach, cuts off along greater gastric curvature, cleans with normal saline, paved to be fixed on the scraps of paper, placed 10% formalin solution fixing, be prepared into section after, microscopy.
Four, microscopy standard, mirror is observed down and mainly contain mononuclear cell, lymphocyte and plasmocyte infiltrating (hereinafter to be referred as inflammatory cell) in the coat of the stomach tissue is chronic gastritis, size according to inflammatory cell infiltration density, we are divided into level Four with chronic gastritis, the person negative (one) that has the inflammatory cell infiltration is not seen in observation under the mirror, the inflammatory cell infiltration that only a few is arranged is a slight chronic gastritis (+), there is more inflammatory cell infiltration person to be moderate chronic gastritis (++), during the cellular infiltration increase in density, be severe chronic gastritis (+++).
Experimental result:
1, ordinary circumstance is observed: in the process of the test, the dietary amount hair of animal does not have obvious change.Body weight change, each stage does not have the evident regularity variation, learns by statistics and handles nonsignificance (p＞0.05).Experimental result sees attached list 1.
2, perusal: when control animals is cutd open inspection, as seen myxedema is arranged, also can be observed pale and a small amount of petechial hemorrhage sometimes.The visible slight rotten to the corn phenomenon of minority is when prevention group and treatment treated animal cut open inspection, except that individual animal has above-mentioned symptom.There is no typical chronic gastritis pathology state.
3, microscopy result, see Table ~ 2 ~ 4
(1) table 2 result analyzes between U=3.038＞2.58 P＜0.01 liang group difference through Ridit extremely significantly meaning, illustrate that sieve drink that rubs is significantly to the preventive effect of experimental chronic gastritis, can reduce its incidence rate greatly.
(2) table 3 is to use 14 days result of MOLUO DAN treatment, and sieve that rubs is drunk low dose of treatment group and carried out Ridit analysis U=2.166 P＜0.05 with matched group and have remarkable meaning.Pill treatment group compares also significance of U=2.172 P＜0.05, (p＞0.05) no marked difference between two treatment groups with it.Sieve is drunk heavy dose of treatment group and matched group though rub
Do not haveRemarkable meaning (P＞0.05), but from table.
Table 1 prevention group and matched group body weight change (X ± SD)
Time
Group example number
When putting to death in 14 days when initial (58 days)
166.33± 207.50± 238.50±
Matched group 12
17.07 29.06 49.60
171.17± 213.50± 217.17±
Prevention group 12
16.02 36.42 29.60
Treatment group and matched group body weight change (X ± SD)
Time
Group example number
Treatment 14 treatments are 23 days behind the model beginning model
Low dose 12 227.91 ± 262.23 ± 271.17 ± 277.67 ±
37.29 46.67 52.09(n＝6) 63.06(n＝6)
Heavy dose 12 221.64 ± 247.72 ± 259.40 ± 254.33 ±
30.79 35.46 39.24(n＝6) 13.65(n＝6)
Pill 12 217.58 ± 255.42 ± 266.17 ± 272.17 ±
26.54 35.13 38.75(n＝6) 45.82(n＝6)
Contrast 12 195.50 ± 230.17 ± 197.00 ± 224.67 ±
11.33 14.16 11.70(n＝6) 26.01(n＝6)
The table 2 sieve drink prevention group experimental result of rubbing
Degree
Group
Add up to the model incidence rate
- +++ +++
Matched group 01236 100%
Prevention organizes 9210 12 25%
The table 3 14 days experimental results of sieve drink treatment of rubbing
Degree
Group
Add up to cure rate
- + ++ +++
Matched group 005160
Small dose group 31206 50%
Heavy dose of group 032050
The pill 22206 33.33% tables 4 23 days experimental results of sieve drink treatment of rubbing
Degree
Group
Add up to cure rate
- + ++ +++
Matched group 004150
Small dose group 31206 50%
Heavy dose of group 022040
Pill 22206 33.33%
The inflammatory cell infiltration degree is alleviated.
(3) table 4 is results of 23 days groups of treatment.Treatment group and matched group carry out Ridit analysis, small dose group (u=2.100, P＜0.05) and pill group (u=2.10 p＜0.05) respectively and have remarkable meaning, and cure rate is identical with table 3.Heavy dose of treatment group and matched group nonsignificance (p＞0.05)
Use immunization method and prepare slow gastritis animal model, its success rate is up to 100%, repeatability, good stability.Mirror is observed down inflammatory cell infiltration and mainly is distributed in mucosa and mucosa eyeball layer and placenta percreta, and it is bigger to soak into density, and minority has congested phenomenon, along with the court of a feudal ruler length of time there is no the trend of recovering voluntarily, does not also observe intestinal epithelial metaplasia and atrophic lesion.
Take the rat of sieve drink that rubs in advance, the incidence rate of chronic gastritis animal model is reduced to 25 inflammatory cell infiltration density and does not all surpass (++), does not see that at mucous layer inflammatory cell infiltration is arranged, and does not have congested phenomenon.Point out sieve drink that rubs to have protective effect to gastric mucosa.The result shows that it is extremely significant that sieve that rubs is drunk the preventive effect of experimental chronic gastritis animal model.
Give rub sieve drink and Luo Dan of low dose and treated 14 days, cure rate is respectively 50% and 33.3%.The rat mucous layer inflammatory cell infiltration density of Zhi Yuing does not obviously reduce yet.No significant difference between two-form.Though the therapeutic effect of heavy dose of group is lower than the above two, does not see inflammatory cell infiltration at mucous layer, tela submucosa and placenta percreta have inflammatory cell infiltration.Finally, soak into density and decrease the trend that take a favorable turn.Treated 23 days, treatment rate is identical with 14 days groups.Inflammatory cell infiltration density does not have big difference, at the visible inflammatory cell infiltration of mucous layer.
In sum, sieve that rubs drink does not all have obvious influence to dietary amount and the body weight of rat, fails to illustrate that it has Nutrition.Sieve that rubs drink can reduce the incidence rate of experimental chronic gastritis animal model greatly, has to give anti-effect significantly.Rub sieve drink of low dose is close with the therapeutic effect of pill.No marked difference (p＞0.05).Cure rate reaches 50%, and other rat pathology degree of not curing is alleviated, and is to give a kind of desirable Chinese patent medicine anti-and the treatment chronic gastritis.
Experimental example 2Sieve that rubs drink is to the mensuration of the stripped stomach sill strip contractility of rat
Material: medicine: sieve that rubs drink (10 milliliters contain 10 gram MOLUO DAN crude drugs, 100% solution), supply with Handan pharmaceutical factory.MOLUO DAN: (9.0 gram pill+30ml distilled water become 13% solution approximately) supplies with Handan pharmaceutical factory.Normal saline
Instrument: LH586-1 type water bath with thermostatic control; The little pulling force sensor of ZH-5 type; LZ6 type three-pen recorder; Little oxygen bucket; Perifusion pipe animal: rat.Body weight: sieve that rubs drink: 273.66 ±
Draw materials: the preparation of the stomach sill strip that exsomatizes, get rat executions of tapping the head, the full stomach of taking-up of cutting open the belly immediately.Then with stomach undercutting slivering, long 2cm, wide 0.3cm puts into the plate of equipment gansenShi liquid, and is standby.
The experiment grouping: get 24 of healthy white rats, make the stomach sill strip according to last method, be divided into following 16 groups at random, it is 10 that sieve that rubs drink is divided into matched group (normal saline) 100% concentration 0.2ml, 0.4ml, 0.6ml and concentration dilution
-4, 10
-3, 10
-2, 10
-1Eight groups (N=12), it is 10 that MOLUO DAN is divided into matched group (normal saline) 13% concentration 0.2ml, 0.4ml, 0.6ml and concentration dilution
-4, 10
-3, 10
-2, 10
-1Eight groups, (N=12)
Experimental technique: after the extracorporeal surface perfusion device installed, with the stomach sill strip two ends ligature of having got ready the pipe that overflows of packing into, one fixing, and No.1 being connected on the transducer probe used with memorandum.Among the figure really, 3 pipes connect waters bath with thermostatic control.Constant with temperature in the maintenance central canal, 95%O is used in nutrition earlier
2+ 5%CO
2Saturated.After water bath with thermostatic control is heated, in the interlayer of bathing pipe, heat again, then flow into central authorities and bathe pipe by managing 4.Administration is directly thrust syringe needle in the rubber tube of connection tube 4 and is injected.
Water temperature is 37 ℃ in the water bath with thermostatic control.Oxygen supply amount (gaseous mixture 95%O
2, 5%CO
2) interior 8～10 bubbles of oxygen-supply quantity of nutritional solution/minute.
Experimental result: see the following form 5,6
Rub sieve drink of table 5 influences N=12 to what the stomach bar shrank
Amplitude (cm) matched group (normal saline) 0.2ml 0.28 ± 0.15 that dosage stomach bar shrinks
10
-4 0.2ml 5.00±2.46
10
-3 0.2ml 4.46±2.35
10
-2 0.2ml 4.57±2.34
10
-10.2ml 5.31 ± 2.31 stock solutions (100%)
0.2ml 7.48±2.17
0.4ml 10.20±2.50
0.6ml 10.86±2.37
Table 6 MOLUO DAN is to the N=12 that influences of stomach bar contraction
The amplitude (cm) that dosage stomach bar shrinks
Matched group (normal saline) 0.2ml 0.48 ± 0.20
10
-4 0.2ml 1.80±0.59*O
10
-3 0.2ml 1.71±0.44*O
10
-2 0.2ml 1.61±0.49*O
10
-1 0.2ml 2.24±0.69*O
Stock solution
0.2ml 4.05±0.99*O
0.4ml 5.33±0.95*O
0.6ml 6.70±0.98*O
Annotate: the * various dose compares p＜0.01 with contrast dosage
The oral liquid of O Isodose and pill be p＜0.05 relatively
For the relation of piecewise analysis medicine (oral liquid, pill) and effect, medicine is divided into heavy dose (stock solution 100%0.2ml, 0.4ml, 0.6ml) respectively to the spy and low dose (white stock solution 100%) dilution is 10
-4, 10
-3, 10
-2, 10
-1) two groups do regression analysis, analysis result shows: heavy dose of group and small dose group all are respectively the effects (p＜0.05) that the effect of oral liquid is much higher than pill.
No matter oral liquid or pill.10
-4, 10
-3, 10
-2, 10
-1(amount is 0.2ml) presents linear relationship along with the contractility of the increase stomach sill strip of dosage increases between dosage and the reaction within the concentration range.The former is y=8.46x+6.13.R=0.94, the latter are y=6.62x+2.38, x=0.98
At oral liquid, pill dosage is 0.2,0.4, within the 0.6ml scope, and along with dosage increases, shrinkage amplitude increases, and the former is y=6.34x+4.66, r=0.78, latter y=5.38x+1.69, r=0.93
More than the determined collinear collimation of two equations relatively all indifference (p＞0.05) therefore, the reliable r of phase relation number average＞0.9.
As seen experiment herewith rubs, and sieve is drunk and MOLUO DAN can increase the stripped stomach bar contractility of rat.
Herba Artemisiae Scopariae, Endothelium Corneum Gigeriae Galli are arranged the MOLUO DAN Main Ingredients and Appearance and Endothelium Corneum Gigeriae Galli has functions such as invigorating the stomach and promoting digestion, and cure mainly food stagnation etc., and MOLUO DAN has functions such as regulating the stomach and sending down the abnormal ascending QI, spleen invigorating relieving distension again.Therefore it is stronger to stomach bar contractility from above result, and can also advance intestinal motility, can advance food digestion, for the existing partial symptoms of chronic gastritis, can obtain good effect.
Experimental example 3Sieve that rubs drink is to the influence of the stomachial secretion function of rat experiment chronic gastritis
Materials and methods: healthy Wistar rat is selected in experiment for use, and totally 83, the male and female dual-purpose.Body weight 227.91 ± 37.29g (X ± SD) is divided into following each group at random, tests and finishes to experiment in preceding 2 months, feeds the 1st group with standard feed, matched group, and with 3 of rats, normal saline is irritated stomach, once-a-day, totally one week.The 2nd group, sieve that rubs drink is to normal rat day secretion function effect.Get 3 of rats.The year drink 0.35ml/100g that rubs irritates stomach, and once a day, the 3rd group of totally one week, MOLUO DAN influences normal rat stomach secretory function, gets 8 of rats, and MOLUO DAN solution 0.3ml/100g irritates stomach, and once a day, in totally one week, ball solution is joined the field and is.Take by weighing 18g shovel MOLUO DAN, place mortar, add the 31ml normal saline and will grind to form suspension.The 4th group, experimental chronic gastritis group.Get 16 of rats, form the gastritis model by the immunoreation method.The 5th group, sieve that rubs drink prevention group.Get big shortsighted 1, sieve that rubs drink is irritated stomach 0.7ml/100g.Once-a-day, totally 4 weeks, and drink first-class week in taking sieve that rubs, finish the group method on time and form the chronic gastritis model.The 6th group, MOLUO DAN treatment group is got 32 of rats, begins administration after the gastritis model forms.Sieve that rubs drink was divided into for 2 week and 3 weeks with the course of treatment of MOLUO DAN, and the therapeutic dose of each group is respectively, and sieve that rubs drink 0.35ml/100g irritates stomach once a day, and sieve that rubs drink 0.7ml/100g irritates stomach once a day, and MOLUO DAN 0.30ml/100g irritates stomach once a day.
The index of stomachial secretion function.The gastric secretion total amount.Gastric total acidity and white enzymatic activity of stomach dawn.
The gastric juice collection method: each treated animal is in collecting gastric juice fasting (can't help water) in preceding 24 hours.In descending deep and remote six ligations of the slight anesthesia of ether.After 4 hours, put to death animal with cervical vertebra from disconnected method, operative incision is opened,, then full stomach is taken out earlier with the rapid ligation of cardia and esophagus junction, cut an osculum along big curved side, gastric content is collected in the test tube, centrifugal 20 minutes, gets its whole supernatant as 4 hours gastric secretion total amounts, get pure gastric juice 1ml again, with 0.01N NaOH solution titration and calculate 4 hours total acidity (uEg/4hr)
Measure proteinase activity by mett protein pipe method. the enzymatic activity computing formula is:
4 pipe meansigma methodss
2* 16 (units)
The MOLUO DAN preparation provides with Handan pharmaceutical factory, and sieve that rubs drink concentration is that every ml contains crude drug 1g.10ml/ and props up lot number: the every ball net weight of 880102. MOLUO DAN 9g, and its crude drug and close ratio are 1: 1.2～1: 1.3, every ball contains about crude drug amount 3.9g.
The experiment data that obtain are all imported the Apple-II microcomputer and are handled, and calculate the significance difference by " T " method of inspection.
The result
Experimental result sees following each table for details;
Table 7 MOLUO DAN is to the influence of normal rat stomach secretory function (X ± SD)
Group example number gastric secretion gastric acidity pepsin activity
(ml/4h) (mEq/4h) (U)
Contrast 8 6.27 ± 2.11 738.18 ± 149.42 38.66 ± 17.88
Oral liquid 8 7.5941.36
B*752.33 ± 238.70
B*62.77 ± 21.11
A**b*
Pill 8 9.16 ± 2.40 740.27 ± 376.69 73.64 ± 21.76
A***
A: compare b: compare * p＞0. with the pill group with matched group
05**p＜0.05***p＜0.01
Table 8 rubs sieve drink prevention administration to the influence of chronic gastritis Mus stomachial secretion function (X ± SD)
Example gastric secretion gastric acidity pepsin activity
Group
Number (ml/4h) is (U) (mEq/4h)
Chronic gastritis
Δ5 5.2 ± 1.85 5.42 ± 9.49 0.67 ± 0.92
Prevention organizes 11 9.26 ± 1.18
A.b**876.17 ± 171.42
A**b*76.71 ± 46.4
A***b**
Matched group 8 6.27 ± 2.11 738.18 ± 149.42 38.66 ± 17.88
Δ is from immunoreation the 44th day sampling and measuring that begin
A: compare b: compare * p＞0.05**p＜0.05***p＜0.01 with the saline control group with the chronic gastritis group
2 weeks of table 9 treatment are to the influence of chronic gastritis Mus stomachial secretion function (X ± SD)
Gastric secretion gastric acidity pepsin activity group example number
(ml/4h) (mEq/4h) (U) chronic gastritis
Δ5 4.4 ± 0.98 409.72 ± 112.47 15.75 ± 6.16 oral liquid 6 7.0 ± 0.99 654.40 ± 254.44
*40.75 ± 15.32
A**0.35ml/100g 0.70ml/100g 4 8.8 ± 0.80
a1092.4 ± 872.92
* *51.16 ± 26.52
A**Pill 0.30ml/100g 6 7.1 ± 1.60
A**b*791.1 ± 224.86
A**b*117.92 ± 59.85
A.b**Δ is from immunoreation the 58th day sampling and measuring a that begin: with chronic gastritis group b relatively: with low dose of oral liquid relatively * p＞0.05**p＜0.05***p＜0.01 table 10,3 weeks of treatment to the influence of chronic gastritis Mus stomachial secretion function (X ± SD)
Gastric secretion gastric acidity pepsin activity
Group example number
(ml/4h) (mEq/4h) (U) chronic gastritis
Δ6 4.27 ± 1.72 348.13 ± 146.07 37.96 ± 12.44 oral liquids 5 6.28 ± 1.22
A**480.35 ± 77.87
Ab46.20 ± 23.68
A*0.35ml/100g0.70ml/100g 6 8.30 ± 1.15
A**855.43 ± 150.75
A**90.79 ± 30.46
A**0.30ml/100g 5 6.26 ± 2.36
A.b*768.08 ± 318.18
A**b*68.34 ± 30.84
A.b*Δ is from immunoreation the 65th day sampling and measuring a that begin: with chronic gastritis group b relatively: with low dose of oral liquid * p＞0.05**p＜0.05***p＜0.01 relatively
Experiment shows that sieve that rubs drink (0.35ml/100g) can significantly improve normal rat gastric juice and proteinase activity (comparing p＜0.05 with matched group), and very little to normal rat stomach liquid and gastric acid influence.Simultaneously, two kinds of dosage forms are that MOLUO DAN and Mo Luo drink the basically identical that influences to normal rat stomach secretory function.So can think the selective effect that improves the stomachial secretion function of this medical instrument.Although the mechanism of this effect waits to inquire into,, expanded the clinical scope of application of sieve drink that rubs at least with regard to its meaning, positive reason subordinate, this medical instrument has the increase pepsin activity, and the effect of facilitating digestion is to the chronic digestive system disease patient, also can significantly improve digestive function, appetite strengthening is alleviated poor appetite, the symptom that digestive system functions such as feeling of fullness are bad, therefore, chronic digestive system disease had more general clinical meaning.
Experiment shows that sieve that rubs drink (0.2ml/100g) can prevent the generation of chronic gastritis preferably.Oral this medicine of rat is totally 4 weeks, forms experimental gastritis model then, and chronic gastritis takes place none example, and morphological observation stomach function regulating secretory function is measured all and normal healthy controls group indifference, and wherein some stomachial secretion functional parameter also improves than matched group.
Experiment shows that also the treatment of different course MOLUO DAN is organized experimental chronic gastritis and all demonstrated curative effect preferably.Sieve that rubs drink and MOLUO DAN relatively, the curative effect basically identical, only in indivedual indexs and course of treatment group, the therapeutical effect of MOLUO DAN sieve drink that rubs is slightly high, whether with in the pill this contain more relevant being worthy of consideration of close composition.
By experiment, we think that the Luo Yinneng that rubs promotes pepsin activity under the normal condition and do not improve gastric acid.Experimental chronic gastritis there are tangible prevention and effect.The drug effect basically identical of two kinds of dosage forms.This poison of drug property is low, and attached effect is few, has clinical value widely.
Experimental example 4Sieve that rubs drink is to white mice intestinal propulsion exercise testing medicine: sieve that rubs drink (10 milliliters contain 10 gram MOLUO DAN crude drugs 100% oral liquid), supply with Handan pharmaceutical factory.
Sieve that rubs is drunk (pill is dissolved in being mixed with in the distilled water contains crude drug 100% solution), supplies with Handan pharmaceutical factory.
Arabic gum suspension 5 gram charcoals end ÷ gram arabic gums in charcoal end are put into mortar earlier, gradually the 100MI distilled water is ground then, suspension).
Normal saline
Instrument: syringe 1MI, filling stomach syringe needle, operating theater instruments, surgery shears, ophthalmology tweezers plank meter ruler (1 meter).
Animal: half and half every group 10 totally 30 of white mice male and female
Body weight: matched group: 19.4 ± 1.07 grams
Oral liquid group: 18.6 ± 0.69 grams
Pill group: 18.4 ± 0.76 grams
Experimental technique: the white mice that selects 18 ~ 22 gram male and female half and half, 10 is one group, be divided into three groups, after testing fasting in preceding 24 hours, elder generation's perfusion is in high spirits, irritate charcoal end suspension (0.2ML/20 gram) again, use the cervical vertebra dislocation method with sacrifice of animal after 20 minutes, cut open the belly immediately the digestive tract cardia to the complete extraction of rectum end, do not add tractive, be tiled in and be with on the graduated meter ruler, survey its total length, the forward position of writing down the charcoal end simultaneously is to the distance of cardia, calculates the percentage ratio of itself and gastrointestinal tract total length, gets full cell mean and compares.
Experimental result: 11 tables 11 that see the following form sieve drink and MOLUO DAN the influence that rubs to the white mice intestinal propulsion
Group dosage charcoal end operation ratio %%
Matched group n=10 0.2ML/20g 54.67 ± 5.60
Sieve that rubs drink n=10 0.2ML/20g 63.82 ± 8.48**
Sieve that rubs drink n=10 0.2ML/20g 62.95 ± 2.96**
Annotate: * * and matched group compare: p＜0.05
+ sieve drink group compares with rubbing: p＞0.05
The Chinese medicine MOLUO DAN has the effect of regulating the stomach and sending down the abnormal ascending QI, spleen invigorating relieving distension, dredging collateral to stop pain, and experimental result shows, the soft DANJI of rubbing sieve drink that rubs has progradation to the white mice small intestinal, thus can the mitigate the disease partial symptoms, and effect is more satisfactory.
Experimental example 5Sieve that rubs drink treatment chronic atrophic gastritis one, clinical data
Observe that case derives from all that Second Hospital Attached To Tianjin Chinese Medicine College is in hospital or six people that diagnose a disease, diagnostic criteria, according to the national standard (summary) that digests sick specialized conference and national atrophic gastritis cooperative groups proposition in 1984 of nineteen eighty-two, and conform to the pertinent regulations of Handan pharmaceutical factory, gastral cavilty portion pain is arranged, symptoms such as distension, the different chronic atrophic gastritis patient who has gastroscope and pathology to make a definite diagnosis in recent (in month).50 routine patients are divided into sieve drink group (observation case) 25 people that rub at random, MOLUO DAN group (contrast case) 25 people, and male's 29 examples wherein, women's 21 examples, the age, the course of disease was 1 month-30 years in 37-78 year.Two, Therapeutic Method
Sieve drink group of rubbing: oral sieve drink that rubs, three times on the one, one time 1-2 props up (10-20-t), and taking medicine before meal is used.
The MOLUO DAN group: oral MOLUO DAN, three times on the one, a 1-2 ball, taking medicine before meal is used.
Three months is a course of treatment, diet cold between period in a medicine is annotated, hard, heat, boiling hot, excitant food and wine, strong tea, coffee etc., and withdraw other Chinese and western drugs, the situation of periodic logging clinical symptoms change meter in the observation of curative effect table is checked gastroscope and pathology when treating and finish simultaneously.
Observe medicine: sieve that rubs drink and MOLUO DAN are Handan pharmaceutical factory to be provided.Three, efficacy assessment standard
Carry out Comprehensive Assessment according to gastroscope and pathological examination results and clinical symptoms change before and after the treatment, curative effect is divided into recovery from illness, produce effects, effective, invalid level Four (particular content sees following Handan institute of pharmaceutical factory enclosure material for details).Four, observed result
The total effective rate of sieve drink group of rubbing treatment chronic atrophic gastritis is 92%, and the total effective rate of MOLUO DAN group treatment chronic atrophic gastritis is 80%.Two groups of curative effects relatively see following table for details.
Sieve that rubs drink, MOLUO DAN treatment chronic atrophic gastritis curative effect and comparison (routine number/letter proportion by subtraction)
Total routine number recovery from illness produce effects enabledisable total effective rate
Sieve that rubs drinks 25 7 (28%) 12 (48%) 4 (16%) 2 (8%) 23 (92%)
MOLUO DAN group 25 5 (20%) 9 (36%) 6 (24%) 5 (20%) 20 (80%)
P value＞0.05＞0.05＞0.05＞0.05＞0.05
Observed result is learned processing, X by statistics
2Inspection danger, P value is equal＞and two groups of curative effect difference of 0.05. do not have the significance meaning.
This observation checking: sieve that rubs drink and MOLUO DAN comparing difference significance, evident in efficacy because of its improvement clinically, and have clothes convenient to symptom, comfortable taste, advantage such as have no adverse reaction is accepted by the patient with agent is easier, worthly applies socially.The following example all can be realized the effect of above-mentioned experimental example.
Embodiment 1Oral liquid
Bulbus Lilii 60g Poria 60g Radix Scrophulariae 75g
Rhizoma Chuanxiong 45g Endothelium Corneum Gigeriae Galli＜stir-fry) 15g Radix Linderae 45g
Rhizoma Alismatis 45g 75g Radix Ophiopogonis Radix Notoginseng 15g
The Rhizoma Atractylodis Macrocephalae＜parched with bran) 30g Radix Angelicae Sinensis 45g Herba Artemisiae Scopariae 60g
Radix Sanguisorbae 75g Pollen Typhae 45g Rhizoma Corydalis (processed with vinegar) 60g
Radix Paeoniae Alba 150g Herba Dendrobii 75g Rhizoma Anemones Altaicae 45g
More than 18 the flavor, decoct with water secondary, each 2 hours, collecting decoction, filter, filtrate is concentrated in right amount, adds ethanol, makes to contain alcohol and measure and reach 70%, leave standstill, filter, reclaim ethanol, filtrate concentrates, add water-cooled and hide, filter, it is an amount of that filtrate adds refined honey, adds water to 1000ml, stir evenly, it is an amount of to add medicinal charcoal again, is filtered to clear and bright, embedding, fiery bacterium, promptly.Oral, a 10～20ml, 3 times on the one; Taking medicine before meal is used.Diet irritable food and beverage; The careful usefulness of anemia of pregnant woman.Every dress 10ml.
Embodiment 2Granule
Bulbus Lilii 70g Poria 70g Radix Scrophulariae 65g
Rhizoma Chuanxiong 35g Endothelium Corneum Gigeriae Galli＜stir-fry) 20g Radix Linderae 50g
Rhizoma Alismatis 40g 70g Radix Ophiopogonis Radix Notoginseng 20g
The Rhizoma Atractylodis Macrocephalae＜parched with bran) 25g Radix Angelicae Sinensis 50g Herba Artemisiae Scopariae 65g
Radix Sanguisorbae 65g Pollen Typhae 55g Rhizoma Corydalis (processed with vinegar) 55g
Radix Paeoniae Alba 160g Herba Dendrobii 60g Rhizoma Anemones Altaicae 40g
More than 18 flavors, decoct with water secondary, each 2 hours, collecting decoction filtered, filtrate is concentrated in right amount, add ethanol, make to contain the alcohol amount and reach 70%, leave standstill, filter, reclaim ethanol, be condensed into cream, add auxiliary materials and mixing such as dextrin, granulate, drying, granulate, packing, promptly.Oral, one time 1～2 bag, 3 times on the one; Taking medicine before meal is used.Diet irritable food and beverage; The careful usefulness of anemia of pregnant woman.Every packed 8 grams.
Embodiment 3The method of quality control of oral liquid formulations is differentiated:
A. get this product 20ml,, extract 2 times with the ether jolting to 2-3 with hydrochloric acid adjusting pH value, each 25ml merges ether solution, and evaporate to dryness, residue add methanol 1ml makes dissolving, as supplying the brilliant solution of examination; Other gets and does not eat in acid contrast crystalline substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 2～5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel C lamellae of adhesive with the sodium carboxymethyl cellulose, with 6: 3: 1 toluene-ethyl acetate-formic acid was developing solvent, launch, take out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
B. get this product 30ml, add the chloroform jolting and extract 2 times, each 20ml, combined chloroform liquid, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Herba Artemisiae Scopariae control medicinal material 2g, adds water 60ml, and reflux 30 minutes is put coldly, filters, and adds chloroform and shines medical material solution in pairs with legal system; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 5-10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the Sodium Tvlose, with 2: 1 petroleum ether (30-60 ℃)-ethyl acetates was developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution-ethanol (1: 3) solution of new preparation, and it is clear to be heated to the speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
C. get this product 20ml, add n-butyl alcohol 25ml, jolting is extracted, and divides and gets n-butyl alcohol liquid, evaporate to dryness, residue dissolves with small amount of methanol, by 200 orders, and 2g, internal diameter 1cm neutral alumina post is with methanol 20ml eluting, collect eluent, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material 2g, adds water 30ml, decocts 30 minutes, filters, and filtrate adds n-butyl alcohol 25ml, and jolting is extracted, and divides and gets n-butyl alcohol liquid, and evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution; Get the peoniflorin reference substance again, add methanol and become every 1ml to contain the solution of 1mg, product solution in contrast; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 3～8 μ l of above-mentioned three kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 5: 3: 1: 1 ethyl acetate-butanone-formic acid-water was developing solvent, launched, and took out, dry, spray is with 5% vanillin sulfuric acid solution-alcoholic acid mixed solution, and vanillin sulfuric acid solution-alcoholic acid ratio is 2: 8, and it is clear to be heated to speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show an identical punctation: with the corresponding position of reference substance on, show identical blue spot.
Assay: measure according to high-efficient liquid phase technique (appendix VID of Chinese Pharmacopoeia version in 2000), chromatographic condition and system suitability test, be filler with octadecylsilane chemically bonded silica: second eyeball-0.1% phosphoric acid solution was a mobile phase in 20: 80; The detection wavelength is 230nm; Number of theoretical plate calculates by the peoniflorin peak should be not less than 1500; The preparation of reference substance solution, the peoniflorin reference substance is an amount of, and accurate the title, decide, and adds 50% methanol and make the solution that every 1ml contains 0.1mg, promptly; The preparation of need testing solution: this product under the loading amount item, mixing, precision is measured 10ml, puts in the separatory funnel, add water 10ml, shake up, extract 5 times, each n-butyl alcohol 20ml with water saturated n-butyl alcohol jolting, 20ml, 20ml, 15ml, 15ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add 50% methanol makes dissolving, moves in the 25ml measuring bottle, and be diluted to scale, and shaking up, precision is measured 5ml, puts in the 25ml measuring bottle, add 50% methanol and be diluted to scale, shake up, filter, promptly; Algoscopy: the accurate respectively brilliant solution of contrast and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; Every of this product contains the Radix Paeoniae Alba in peoniflorin (C
23H
28O
11) meter, must not be less than 5.0mg.
Claims (11)
1, a kind of Chinese medicine compositions for the treatment of chronic atrophic gastritis is characterized in that this pharmaceutical composition made by following raw material medicaments:
Bulbus Lilii 50-70 weight portion Poria 50-70 weight portion Radix Scrophulariae 60-90 weight portion
Rhizoma Chuanxiong 30-50 weight portion Endothelium Corneum Gigeriae Galli 10-20 weight portion Radix Linderae 30-50 weight portion
Rhizoma Alismatis 30-50 weight portion 60-90 Radix Ophiopogonis weight portion Radix Notoginseng 10-20 weight portion
Rhizoma Atractylodis Macrocephalae 20-40 weight portion Radix Angelicae Sinensis 30-50 weight portion Herba Artemisiae Scopariae 50-70 weight portion
Radix Sanguisorbae 60-90 weight portion Pollen Typhae 30-50 weight portion Rhizoma Corydalis 50-70 weight portion
Radix Paeoniae Alba 130-170 weight portion Herba Dendrobii 60-90 weight portion Rhizoma Anemones Altaicae 30-50 weight portion.
2. pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition made by following raw material medicaments:
Bulbus Lilii 60 weight portion Poria 60 weight portion Radix Scrophulariaes 75 weight portions
The Rhizoma Chuanxiong 45 weight portion Endothelium Corneum Gigeriae Galli 15 weight portion Radixs Linderae 45 weight portions
Rhizoma Alismatis 45 weight portion 75 weight portion Radix Notoginseng Radix Ophiopogonis 15 weight portions
The Rhizoma Atractylodis Macrocephalae 30 weight portion Radix Angelicae Sinensis 45 weight portion Herba Artemisiae Scopariaes 60 weight portions
Radix Sanguisorbae 75 weight portion Pollen Typhaes 45 weight portion Rhizoma Corydalis 60 weight portions
The Radix Paeoniae Alba 150 weight portion Herba Dendrobiis 75 weight portion Rhizoma Anemones Altaicaes 45 weight portions.
3. as claim 1,2 described pharmaceutical compositions, it is characterized in that Rhizoma Atractylodis Macrocephalae parched with bran described in this pharmaceutical composition, the Rhizoma Corydalis processed with vinegar, Endothelium Corneum Gigeriae Galli is selected Endothelium Corneum Gigeriae Galli (parched) for use.
4. preparation of drug combination method as claimed in claim 3, it is characterized in that this method is: above 18 flavors, decoct with water 1-3 time, each 1.5-3 hour, collecting decoction filters, and filtrate is concentrated in right amount, add ethanol, make to contain alcohol amount and reach 60-80%, leave standstill, filter, reclaim ethanol, filtrate concentrates, and adds water-cooled and hides, and filters, at last directly or add pharmaceutically acceptable excipient and make clinical acceptable forms, as tablet, capsule, granule, suspensoid, drop pill, oral liquid through conventional operation.
5. preparation of drug combination method as claimed in claim 4 is characterized in that the preparation method of oral liquid formulations is: above 18 flavors decoct with water secondary, each 2 hours, collecting decoction filters, and filtrate is concentrated into relative density 1.10～1.15, adds ethanol, make to contain alcohol amount and reach 70%, leave standstill, filter, reclaim ethanol, filtrate concentrates, and adds water-cooled and hides, and filters, and filtrate adds 10% refined honey, add water to 1000ml, stir evenly, add medicinal charcoal 28～33g again, be filtered to clear and bright, embedding, sterilization, promptly.
6. as the sharp method of quality control that requires 3 described drug composition oral liquid formulations, it is characterized in that discrimination method in this method comprises one or more in the following discriminating:
A. get this product 20ml,, extract 2 times with the ether jolting to 2-3 with hydrochloric acid adjusting pH value, each 25ml merges ether solution, and evaporate to dryness, residue add methanol 1ml makes dissolving, as supplying the brilliant solution of examination; Other gets and does not eat in acid contrast crystalline substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 2～5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel C lamellae of adhesive with the sodium carboxymethyl cellulose, with 5-7: 2-4: 1-2 toluene-ethyl acetate-formic acid is developing solvent, launches, and takes out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
B. get this product 30ml, add the chloroform jolting and extract 2 times, each 20ml, combined chloroform liquid, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Herba Artemisiae Scopariae control medicinal material 2g, adds water 60ml, and reflux 25-35 minute, put coldly, filter, add chloroform and shine medical material solution in pairs with legal system; Test according to thin layer chromatography, draw each 5-10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the Sodium Tvlose, with 30-60 ℃ of petroleum ether-ethyl acetate is developing solvent, and ratio is 1-3: 0.5-1.5, launches, take out, dry, spray is with 5% vanillin sulfuric acid solution-alcoholic solution of new preparation 0.5-1.5: 2-5, and it is clear to be heated to the speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
C. get this product 20ml, add n-butyl alcohol 25ml, jolting is extracted, and divide and get n-butyl alcohol liquid, evaporate to dryness, residue dissolves with small amount of methanol, by the neutral alumina post, with methanol 20ml eluting, collects eluent, and evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material 2g, adds water 30ml, decocts 25-35 minute, filters, and filtrate adds n-butyl alcohol 25ml, and jolting is extracted, and divides and gets n-butyl alcohol liquid, and evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution; Get the peoniflorin reference substance again, add methanol and become every 1ml to contain the solution of 1mg, product solution in contrast; Test according to thin layer chromatography, draw each 3～8 μ l of above-mentioned three kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 4-6: 2-5: 1-2: 0.5-1.5 ethyl acetate-butanone-formic acid-water is developing solvent, launches, and takes out, dry, spray is with 5% vanillin sulfuric acid solution-alcoholic acid mixed solution, and vanillin sulfuric acid solution-alcoholic acid ratio is 1-3: 7-9, and it is clear to be heated to speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show an identical punctation: with the corresponding position of reference substance on, show identical blue spot.
7. as the sharp method of quality control that requires 6 described drug composition oral liquid formulations, it is characterized in that discrimination method in this method comprises one or more in the following discriminating:
A. get this product 20ml,, extract 2 times with the ether jolting to 2-3 with hydrochloric acid adjusting pH value, each 25ml merges ether solution, and evaporate to dryness, residue add methanol 1ml makes dissolving, as supplying the brilliant solution of examination; Other gets and does not eat in acid contrast crystalline substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 2～5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel C lamellae of adhesive with the sodium carboxymethyl cellulose, with 6: 3: 1 toluene-ethyl acetate-formic acid was developing solvent, launched, and took out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
B. get this product 30ml, add the chloroform jolting and extract 2 times, each 20ml, combined chloroform liquid, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Herba Artemisiae Scopariae control medicinal material 2g, adds water 60ml, and reflux 30 minutes is put coldly, filters, and adds chloroform and shines medical material solution in pairs with legal system; Test according to thin layer chromatography, draw each 5-10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the Sodium Tvlose, with 2: 1 temperature was that 30-60 ℃ of petroleum ether-ethyl acetate is developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution-alcoholic solution of 1: 3 of new preparation, and it is clear to be heated to the speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
C. get this product 20ml, add n-butyl alcohol 25ml, jolting is extracted, and divides and gets n-butyl alcohol liquid, evaporate to dryness, residue dissolves with small amount of methanol, by 200 orders, and 2g, internal diameter 1cm neutral alumina post is with methanol 20ml eluting, collect eluent, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material 2g, adds water 30ml, decocts 30 minutes, filters, and filtrate adds n-butyl alcohol 25ml, and jolting is extracted, and divides and gets n-butyl alcohol liquid, and evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution; Get the peoniflorin reference substance again, add methanol and become every 1ml to contain the solution of 1mg, product solution in contrast; Test according to thin layer chromatography, draw each 3～8 μ l of above-mentioned three kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 5: 3: 1: 1 ethyl acetate-butanone-formic acid-water was developing solvent, launched, and took out, dry, spray is with 5% vanillin sulfuric acid solution-alcoholic acid mixed solution, and vanillin sulfuric acid solution-alcoholic acid ratio is 2: 8, and it is clear to be heated to speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show an identical punctation: with the corresponding position of reference substance on, show identical blue spot.
8. as the sharp method of quality control that requires 3 described drug composition oral liquid formulations, it is characterized in that the content assaying method in this method is: measure according to high-efficient liquid phase technique, chromatographic condition and system suitability test, be filler: 16-25 with octadecylsilane chemically bonded silica: 70-85 second eyeball-0.1% phosphoric acid solution is a mobile phase; The detection wavelength is 230nm; Number of theoretical plate calculates by the peoniflorin peak should be not less than 1500; The preparation of reference substance solution, the peoniflorin reference substance is an amount of, and accurate the title, decide, and adds 45-55% methanol and make the solution that every 1ml contains 0.1mg, promptly; The preparation of need testing solution: this product under the loading amount item, mixing, precision is measured 10ml, puts in the separatory funnel, add water 10ml, shake up, extract 5 times with water saturated n-butyl alcohol jolting, merge n-butyl alcohol liquid, evaporate to dryness, residue add 45-55% methanol makes dissolving, move in the 25ml measuring bottle, and be diluted to scale, shake up, precision is measured 5ml, puts in the 25ml measuring bottle, adds 45-55% methanol and is diluted to scale, shake up, filter, promptly; Algoscopy: the accurate respectively brilliant solution of contrast and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; Present composition oral liquid formulations per unit amount contains the Radix Paeoniae Alba to be counted in peoniflorin, must not be less than 5.0mg.
9. as the sharp method of quality control that requires 8 described drug composition oral liquid formulations, it is characterized in that the content assaying method in this method is: measure according to high-efficient liquid phase technique, chromatographic condition and system suitability test, be filler with octadecylsilane chemically bonded silica: second eyeball-0.1% phosphoric acid solution was a mobile phase in 20: 80; The detection wavelength is 230nm; Number of theoretical plate calculates by the peoniflorin peak should be not less than 1500; The preparation of reference substance solution, the peoniflorin reference substance is an amount of, and accurate the title, decide, and adds 50% methanol and make the solution that every 1ml contains 0.1mg, promptly; The preparation of need testing solution: this product under the loading amount item, mixing, precision is measured 10ml, puts in the separatory funnel, add water 10ml, shake up, extract 5 times, each n-butyl alcohol 20ml with water saturated n-butyl alcohol jolting, 20ml, 20ml, 15ml, 15ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add 50% methanol makes dissolving, moves in the 25ml measuring bottle, and be diluted to scale, and shaking up, precision is measured 5ml, puts in the 25ml measuring bottle, add 50% methanol and be diluted to scale, shake up, filter, promptly; Algoscopy: the accurate respectively brilliant solution of contrast and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; Every of this product contains the Radix Paeoniae Alba to be counted in peoniflorin, must not be less than 5.0mg.
10. the method for quality control of the described drug composition oral liquid formulation of claim 3 is characterized in that this method.Differentiate:
A. get this product 20ml,, extract 2 times with the ether jolting to 2-3 with hydrochloric acid adjusting pH value, each 25ml merges ether solution, and evaporate to dryness, residue add methanol 1ml makes dissolving, as supplying the brilliant solution of examination; Other gets and does not eat in acid contrast crystalline substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 2～5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel C lamellae of adhesive with the sodium carboxymethyl cellulose, with 5-7: 2-4: 1-2 toluene-ethyl acetate-formic acid is developing solvent, launches, and takes out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
B. get this product 30ml, add the chloroform jolting and extract 2 times, each 20ml, combined chloroform liquid, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Herba Artemisiae Scopariae control medicinal material 2g, adds water 60ml, and reflux 25-35 minute, put coldly, filter, add chloroform and shine medical material solution in pairs with legal system; Test according to thin layer chromatography, draw each 5-10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the Sodium Tvlose, with 30-60 ℃ of petroleum ether-ethyl acetate is developing solvent, and ratio is 1-3: 0.5-1.5, launches, take out, dry, spray is with 5% vanillin sulfuric acid solution-alcoholic solution of new preparation 0.5-1.5: 2-5, and it is clear to be heated to the speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
C. get this product 20ml, add n-butyl alcohol 25ml, jolting is extracted, and divide and get n-butyl alcohol liquid, evaporate to dryness, residue dissolves with small amount of methanol, by the neutral alumina post, with methanol 20ml eluting, collects eluent, and evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material 2g, adds water 30ml, decocts 25-35 minute, filters, and filtrate adds n-butyl alcohol 25ml, and jolting is extracted, and divides and gets n-butyl alcohol liquid, and evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution; Get the peoniflorin reference substance again, add methanol and become every 1ml to contain the solution of 1mg, product solution in contrast; Test according to thin layer chromatography, draw each 3～8 μ l of above-mentioned three kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 4-6: 2-5: 1-2: 0.5-1.5 ethyl acetate-butanone-formic acid-water is developing solvent, launches, and takes out, dry, spray is with 5% vanillin sulfuric acid solution-alcoholic acid mixed solution, and vanillin sulfuric acid solution-alcoholic acid ratio is 1-3: 7-9, and it is clear to be heated to speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show an identical punctation: with the corresponding position of reference substance on, show identical blue spot; Assay: measure according to high-efficient liquid phase technique, chromatographic condition and system suitability test, be filler: 16-25 with octadecylsilane chemically bonded silica: 70-85 second eyeball-0.1% phosphoric acid solution is a mobile phase; The detection wavelength is 230nm; Number of theoretical plate calculates by the peoniflorin peak should be not less than 1500; The preparation of reference substance solution, the peoniflorin reference substance is an amount of, and accurate the title, decide, and adds 45-55% methanol and make the solution that every 1ml contains 0.1mg, promptly; The preparation of need testing solution: this product under the loading amount item, mixing, precision is measured 10ml, puts in the separatory funnel, add water 10ml, shake up, extract 5 times with water saturated n-butyl alcohol jolting, merge n-butyl alcohol liquid, evaporate to dryness, residue add 45-55% methanol makes dissolving, move in the 25ml measuring bottle, and be diluted to scale, shake up, precision is measured 5ml, puts in the 25ml measuring bottle, adds 45-55% methanol and is diluted to scale, shake up, filter, promptly; Algoscopy: the accurate respectively brilliant solution of contrast and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; Present composition oral liquid formulations per unit amount contains the Radix Paeoniae Alba to be counted in peoniflorin, must not be less than 5.0mg.
11. the application of pharmaceutical composition as claimed in claim 3 in preparation treatment chronic atrophic gastritis medicine.
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| CN101229323B (en) * | 2008-01-21 | 2014-03-26 | 邯郸制药有限公司 | Lily oral liquid and quality standard and test method of pharmaceutical preparation thereof |
| CN105327150A (en) * | 2015-12-16 | 2016-02-17 | 邯郸制药股份有限公司 | Preparing method for traditional Chinese medicine composition for treating gastritis and preparation |
| CN105381256A (en) * | 2015-12-16 | 2016-03-09 | 邯郸制药股份有限公司 | Traditional Chinese medicine composition for treating gastritis and preparation method thereof |
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2003
- 2003-04-17 CN CNB031218873A patent/CN1239187C/en not_active Expired - Lifetime
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