CN1879711B - A Chinese medicinal composition for treating gastric disease, its preparation process and detection method - Google Patents
A Chinese medicinal composition for treating gastric disease, its preparation process and detection method Download PDFInfo
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- CN1879711B CN1879711B CN200610078696A CN200610078696A CN1879711B CN 1879711 B CN1879711 B CN 1879711B CN 200610078696 A CN200610078696 A CN 200610078696A CN 200610078696 A CN200610078696 A CN 200610078696A CN 1879711 B CN1879711 B CN 1879711B
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Abstract
Disclosed is a Chinese medicinal composition for treating gastritis, stomach pain and gastric acidity, which is prepared from a predetermined proportion of notoginseng, wine-treated rhubarb, alum and ophicalcite, and can be made into tablets, capsules, pills or powders. The invention also discloses the method for preparing the Chinese medicinal composition and its quality control method.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition, especially a kind of Chinese medicine composition that is used for the treatment of gastritis, stomachache, gastric acid belongs to the field of Chinese medicines.
Background technology
Gastropathy is clinical common disease, and it much is erosive gastritis that gastroscopy confirms, brings very big misery to the patient, has had a strong impact on broad masses of the people's health.Though the medicine of treatment gastritis is many, unsatisfactory.Develop quick-acting, efficient and lasting, the low-cost new drug of curative effect, this is a needs of society.Show according to Beijing city-level front three hospital gastroscope binding of pathological reconnaissance information, during the adult organizes more than 20 years old, oneself thinking has pathological changes such as suffering from stomach lining inflammation among the crowd of gastropathy more than 80%, and those think oneself there is not the crowd of gastropathy, also has people more than 70% to suffer from various degree gastropathy.67 examples were erosive gastritiss to Wang Changhong etc., accounted for 55% in 123 routine upper abdominal pain patients of Chinese combination of Chinese and Western medicine magazine report in 1994.Shi Jin etc. 1993 report that in Anhui medical science 72 examples are severe erosive gastritiss in the 194 routine chronic gastritiss.Wang Liying etc. 1996 report that in Jilin medical science 76 routine liver cirrhosis merge the upper gastrointestinal hemorrhage patients, and 63% merges gastric mucosal lesion, examines 8 examples into erosive gastritis, accounts for 11%.Wang Xiu model 1994 is reported 126 routine liver cirrhosis upper gastrointestinal hemorrhage persons at Chinese emergency medicine, and 29% is hemorrhage erosive gastritis.Gastral cavilty distending pain or twinge often appear in erosive gastritis patient, with the gastral cavity painful abdominal mass, and noisy acid regurgitation, wait disease indigestion and loss of appetite just deceiving.Chinese medical discrimination belongs to phlegm resistance, and the phlegm-damp stasis of blood of stagnation of QI-blood stagnates and demonstrate,proves.In a word, gastritis, erosive gastritis are clinical common diseases, and the medicine of exploitation treatment gastritis is a needs of society.
Summary of the invention
The purpose of this invention is to provide a kind of Chinese medicine composition for the treatment of gastritis and intercurrent disease thereof of making; Another purpose of the present invention provides this Chinese medicine composition preparation method and method of quality control.
The objective of the invention is to be achieved through the following technical solutions.
The invention provides a kind of Chinese medicine composition that is used for the treatment of gastritis, this Chinese medicine composition is to be made by the crude drug of following weight ratio: 15～25 parts of Radix Notoginseng, 5～10 parts of Radix et Rhizoma Rhei (processed with wine), 10～20 parts of calcined Alumen, 5～10 parts of calcined OPHICALCITUMs.
After preferred, the proportioning of each crude drug is: 17～20 parts of Radix Notoginseng, 5～8 parts of Radix et Rhizoma Rhei (processed with wine), 15～18 parts of calcined Alumen, 7～9 parts of calcined OPHICALCITUMs.
Further preferred, the optimal proportion that obtains each crude drug is: 19 parts of Radix Notoginseng, 7 parts of Radix et Rhizoma Rhei (processed with wine), 16 parts of calcined Alumen, 8 parts of calcined OPHICALCITUMs.
More than in each crude drug, Radix Notoginseng is meant the dry root of panax araliaceae plant Panax notoginseng (Burk.) F.H.Chen, standard should meet the relevant regulations of state-promulgated pharmacopoeia.Radix Et Rhizoma Rhei is meant the dry root and rhizome of polygonum rheum palmatum Rheum Palmatum L., Rheum tanguticum Rheum tanguticum Maxim.ex Balf. or Rheum officinale Rheumofficinale Baill., and makes Radix et Rhizoma Rhei (processed with wine) by state-promulgated pharmacopoeia or national concocted specification.Calcined Alumen also claims dried Alumen, is meant that Sulfates mineral alunite refines the master who makes through processing and contains aqueous sulfuric acid aluminum potassium [KAL (S0
4)
212H
20] Alumen, calcine loses water of crystallization and forms again.Relevant criterion should meet the regulation of Alumen in the state-promulgated pharmacopoeia.Ophicalcitum is a metamorphic rock rocks ophiolite, excavates the back and removes roguing stone and silt and get, and calcined OPHICALCITUM promptly is with behind the Ophicalcitum calcine and get, and relevant criterion should meet in the state-promulgated pharmacopoeia pertinent regulations under the Ophicalcitum item.
Above crude drug can be made into any in tablet, capsule, pill, the powder as required.No matter make which kind of dosage form, its basic technology is identical, is about to each crude drug pulverize separately and becomes fine powder, feeds intake with clean medicated powder in proportion, and the needs according to dosage form add suitable adjuvant again, and technology is made required dosage form routinely.As make capsule, and can not add any adjuvant, directly get final product dressing up capsule behind each medicated powder mixing.Can certainly add a small amount of hypromellose sodium, behind the mixing, be pressed into tablet.
In order to control product quality, the inventor has also formulated a cover method of quality control, the all items of this method state-promulgated pharmacopoeia regulation, qualitative identification wherein and assay two projects are most crucial parts, qualitative identification wherein is divided into microscopical identification again and thin layer chromatography is differentiated, every content division is as follows:
Microscopical identification: get the powder of invention product, put microscopically and observe, yellow resin canal fragment sees that easily calcium oxalate cluster crystal is big, diameter 60-140um.
Thin layer chromatography is differentiated:
(1) get product powder 1～3g of the present invention, add dilute hydrochloric acid 15ml, heated and boiled also keeps little and boiled 5 minutes, puts cold, filter, get filtrate 2ml, put in the test tube, drip ammonia solution to producing white gels shape precipitation, drip alizarine S test solution number droplet, precipitation becomes cherry red;
(2) get invention product powder 1～3g, put in the tool plug triangular flask, add methanol 10ml, supersound extraction 1 hour is filtered, and gets filtrate as need testing solution; Other gets Radix Notoginseng control medicinal material powder 0.4g, shines medical material solution in pairs with legal system; Get ginsenoside Rg1, arasaponin R1 reference substance again, add methanol respectively and make the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw each 5ul of above-mentioned solution, put respectively on same silica gel g thin-layer plate, under the condition of relative humidity 45% saturated 30 minutes, with volume ratio is that the subnatant that chloroform-methanol-water mixed liquid of 65: 35: 10 is placed below 10 ℃ is developing solvent, launches, and takes out, dry, spray is with 5% ethanol solution of sulfuric acid, in about 10 minutes of 105 ℃ of bakings, in the test sample chromatograph, with reference substance and the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
(3) get invention product powder 1～3g, put in the tool plug triangular flask, add methanol 10ml, supersound extraction 1 hour is filtered, and gets filtrate as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material powder 0.3g, shines medical material solution in pairs with legal system; According to the thin layer chromatography test, draw above-mentioned two kinds of each 8ul of solution, put respectively on same silica gel g thin-layer plate, with volume ratio is that the upper solution of 15: 5: 1 petroleum ether-formic acid second fat-formic acid mixed liquors is developing solvent, launches, and takes out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show 5 identical orange-yellow fluorescence speckles; Put in the ammonia smoked after, speckle becomes orange red.
Assay:
Get product powder 1～2g of the present invention, the accurate title, decide, and puts in the tool plug triangular flask, accurate methanol 10ml, the close plug of adding, claim decide weight, supersound extraction 1 hour is put coldly, and weight decided in title, supplies the weight that subtracts mistake with methanol, shake up, put in the centrifuge tube, after the centrifugalize, get supernatant, as need testing solution; Other gets the ginsenoside Rg1 reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography, draw above-mentioned two kinds of each 5ul of solution, the cross point is on same silica gel g thin-layer plate respectively, with volume ratio is 20: 40: 10: lower floor's solution of chloroform-n-butyl alcohol of 20-methanol-water mixture 5-10 ℃ placement is developing solvent, after under relative humidity 45% condition saturated 20 minutes, launch, take out, dry, spray is with 5% ethanol solution of sulfuric acid, about 10 minutes of 105 ℃ of bakings, clear to the speckle colour developing, take out, on lamellae, cover onesize glass plate, fixing, scan wavelength according to thin layer chromatography: λ S=525nm, λ R=700nm, measure test sample trap integrated value and reference substance trap integrated value, calculate, promptly get the content of ginsenoside Rg1 in the product.
Each crude drug of this Chinese medicine composition, fully according to the theory of Chinese medical science prescription, with the passing of time stomachache, gastral cavity painful abdominal mass, flatulence for the phlegm-damp stasis of blood stagnates do not heal, noisy acid regurgitation, the indigestion and loss of appetite treatment that waits disease is with blood-activating analgetic, and dampness method expectorant is method.The Radix Notoginseng sweet and slightly bitter taste is warm in nature in the side, returns liver stomach warp.Sweet slow temperature is logical, and hardship is fallen and let out, the analgesic therapy of energy dissipating blood stasis, and can eliminate the phlegm, specially control cards such as swelling and pain due to blood stasis, be used for the stomachache card that the phlegm-damp stasis of blood stagnates, in the side, play main therapeutical effect, monarch drug in the side of being.Radix et Rhizoma Rhei (processed with wine) bitter in the mouth gas perfume (or spice) is cool in nature, returns taste large intestine and Liver Channel, blood circulation promoting and blood stasis dispelling, and the regulating QI pain relieving can strengthen the principal agent blood stasis dispelling, and it is descending to draw gastric qi, for minister makes it medicine.It is cold in nature that Alumen is sour and astringent, after the calcine, and the convergence analgesic therapy, removing dampness and eliminating phlegm is adjuvant drug.The misery property of calcined OPHICALCITUM is flat, goes into Liver Channel, and removing stasis to stop bleeding is controlled and spitted blood and the stasis of blood person that holds concurrently, and can relieving gastric hyperacidity to alleviate stomachache.Being used for our removing stasis to stop bleeding, blood is ended and not staying the stasis of blood, also is adjuvant drug.All medicines are harmonious, blood-activating analgetic, removing dampness and eliminating phlegm.Be applicable to that the phlegm-damp stasis of blood stagnates, the stomachache flatulence, noisy acid regurgitation, purplish tongue or ecchymosis is arranged, moist and slippery fur is greasy, diseases such as stringy and thready pulse, and erosive gastritis is seen the phlegm-damp stasis of blood syndrome that stagnates.
The inventor mainly observes the protective effect of the gastric mucosa injury that product of the present invention brings out to rat acetic acid ulcer healing, to absolute alcohol again by zoopery; to effects such as gastric juice, gastric acid, pepsic secretion, pain relievings, and observed it to the inhibitory action of helicobacter pylorus bacteria growing and to the influence of gastric mucosal blood flow.Now be reported as follows:
Experiment material
1, laboratory animal
Wistar is 1 grade of male and healthy rat [word＜8910R016 is moved in the capital 〉], body weight 180-220 gram, 1 grade of the male body weight 20-25 gram of kunming mice [word＜8806M038 is moved in the capital 〉], all provide by Department Of Medicine, Peking University's Experimental Animal Center.Feed with standard feed.
2, experiment medicine
(1) product of the present invention " sharp capsule for treating gastropathy ", the inventor makes by optimal technical solution of the present invention.
(2) sucralfate (sucralfate) was so kind as to give by the S.K.Lam of Mary hospital of Hong Kong University professor in 1993.
(3) tripotassium dicitratobismuthate: by especially big pharmaceutical factory advanced in years product batch number: 93115/51.
(4) aspirin (pure product) is given by Tokyo woman professor H.K.Mori of medical university.Force field pharmaceutical factory produces; 1992 give.
(5) indometacin (pure product) was produced by Beijing the 4th pharmaceutical factory in 1994, was dissolved in 2% sodium bicarbonate solution concentration 5mg/ml, preparation before the experiment.
Experimental technique
Experiment one: sharp capsule for treating gastropathy is to the influence of rats acetic acid gastric ulcer healing and gastric acid, pepsinia.This experiment is burnt gastric ulcer with sharp capsule for treating gastropathy, carafate for treating rats acetic acid, and observes the variation of ulcer healing gastric acid in late period, pepsinia.Sharp capsule for treating gastropathy is dissolved in the distilled water, is mixed with the suspension of variable concentrations, each 1ml (with before shaking up), 2 times on the 1st (down together).
Experimental procedure is as follows:
Ulcer model preparation method: prepare the rats acetic acid gastric ulcer model and also improved (1) with reference to the method for Okabc.Fasting is 24 hours before the art, and etherization is opened abdomen, with the full gland division that is clipped in of acetic acid, injects in the annulus with 50% acetic acid 0.1ml; After treating for 60 seconds, blot intra-annular acetic acid with Cotton Gossypii, take off full folder, use the normal saline flushing coat of the stomach, close abdomen, operation process is by the sterile working.Be divided into 4 groups at random, the normal saline group: (8), to the normal saline of the capacity of grade; Sharp capsule for treating gastropathy group: (8), 188mg/kgd; 2 groups of sharp capsule for treating gastropathy: (8), 376mg/kgd; Sucralfate group: (7): 125mg/kgd.Each organizes the no significant difference of body weight (average 187.30 gram), every day at twice, per os gastric infusion (same down); Administration 11 days.
Gastric juice is collected, acidity stomach function regulating protease assay:
Administration fasting in the 11st day was under etherization opened the abdominal cavity on the 12nd day, and injured blood vessel is avoided in ligation between pylorus and duodenum.It is the vinyl tube of 3mm that per os inserts diameter, is inserted into gastric always, injects warm saline 4ml with syringe, and gastric content is pumped.Send stomach back to abdominal cavity then, sew up the incision, postoperative 3 hours, the reuse etherization is put to death animal, opens otch, in esophagus and the ligation of cardia place, takes out whole stomach, opens pylorus and collects gastric juice, calculates the gastric juice amount, with 0.1NNaOH titration gastric juice.Measure pepsin content (2) in the gastric juice with the Anson of improvement and the method for Mirsky.Concrete steps are as follows:
The drafting of standard curve, tyrosine makees standard substance with tyrosine, be made into 200 μ g/ stock solutions, the time spent with 0.04NHCL be diluted to 50 μ g/ml, 100 μ g/ml, 150 μ g/ml, 200 μ g/ml do transverse axis with concentration of standard solution, the OD value is done the longitudinal axis and is drawn standard curve.Gastric juice 0.1ml+0.04NHCL1.9ml acidify gastric juice is got 0.5ml+2.5% bovine serum albumin 2ml, and 5% trichloroacetic acid 5ml mixes, and places 30 minutes (room temperature), filters; Filtrate 1ml+0.5M sodium carbonate 5ml, 0.5ml phenol liquid is placed more than 60 minutes (room temperature), measures by (640nrn spectrophotometer).
The ulcer area calculates:
Got after the gastric juice,, injected gastric, and put into fixedly gastric outer wall 10 minutes of formalin solution, so that measure the ulcer area with 5% formalin solution 7ml with pylorus ligation again.Cut off along greater gastric curvature, stomach is flattened, use slide calliper rule under anatomical lens, to measure the diameter of ulcer, with the size of its area (mm.mm) expression ulcer.
The result:
(1) sharp capsule for treating gastropathy is to the influence of rat gastric ulcer healing:
The ulcer model that uses has many advantages, and method is easy, and the ulcer size evenly generally healed in 12 days after surgery substantially.The sharp capsule for treating gastropathy of various dose is to the influence such as the table 1 of ulcer healing
The sharp capsule for treating gastropathy of table 1 is to the influence of rat gastric ulcer healing
| Grouping | Quantity (only) | The ulcer area (mm.mm ± SD) | The P value |
| Normal saline | 8 | 5.76±1.12 | |
| Sharp capsule for treating gastropathy (188mg/kg) | 8 | 1.93±0.57 | ＜0.01 |
| Sharp capsule for treating gastropathy (376mg/kg) | 8 | 3.25±0.64 | ＜0.05 |
| Sucralfate (125mg/kg) | 8 | 1.67±0.68 | ＜0.01 |
2.75,5.5 times of rats to people's consumption of sharp capsule for treating gastropathy dosage are organized and the sucralfate group, and the ulcer area is significantly less than matched group.
(2) sharp capsule for treating gastropathy is to the influence of rat gastric juice, gastric acid, pepsinia:
(1) to the influence of gastric secretion, collect 3 hours gastric juice amount, the average 3.13 ± 0.52ml of matched group (X ± SD is down together), 2.75 times to human dose group (sharp capsule for treating gastropathy 188mg/kg group), average 2.33 ± 0.51ml, 5.5 amount group (sharp capsule for treating gastropathy 376mg/kg group) doubly, average 3.34 ± 0.55ml, sucralfate group, average 2.42 ± 0.42ml, sharp capsule for treating gastropathy 188mg/kg group and matched group compare, and the gastric juice amount reduces (p＜0.05), and there were significant differences.Sharp capsule for treating gastropathy 376mg/kg group and matched group do not reduce (table 2) than gastric secretion.
(2) to the influence of gastric acidity, the average 68.3 ± 6.0MEq/L of the average 100.8 ± 4.0MEq/L sucralfate of matched group group, sharp capsule for treating gastropathy group is to not significantly influence (table 2) of gastric acidity.
(3) to the gastric acid influence of output, the average 0.31 ± 0.02MEq/3 of matched group hour, sharp capsule for treating gastropathy 188mg/kg group, average 0.24 ± 0.06MEq/3 hour, sharp capsule for treating gastropathy 376mg/kg group, 0.30 ± 0.05 sucralfate group 0.16 ± 0.03MEq/3 hour.Sharp capsule for treating gastropathy 188mg/kg group, gastric acid output are lacked (p＜0.05), sucralfate group gastric acid meaningful minimizing of output (table 2) than matched group.
(4) the sharp capsule for treating gastropathy group of the influence of pepsinia is not had evident difference to pepsic concentration and output and matched group than all, sucralfate is to pepsic concentration and all significant minimizing of output (table 2).
The sharp capsule for treating gastropathy of table 2 is to the influence of rat gastric acid, pepsinia (X ± SD)
| Grouping | Quantity (only) | Gastric juice amount (ml) | Total acidity MEq/L | Total enzyme output (MEq/3h) | Pepsin concn μ g/ml | Pepsin output μ g/3h |
| Saline | 8 | 3.13±0.52 | 100.8±4.0 | 0.31±0.02 | 600.33±84.2 | 1750.70±29.22 |
| Sharp stomach 1 | 8 | 2.33±0.51* | 104.2±2.3 | 0.24±0.06* | 646.60±89.9 | 1505.18±198.0 |
| Sharp stomach 2 | 8 | 3.34±0.55 | 92.1±1.6 | 0.30±0.05 | 674.28±38.8 | 2019.20±192.5 |
| Sucralfate | 7 | 2.42±0.42* | 68.3±6.0** | 0.16±0.03** | 255.0±54.2** | 617.10±82.0** |
Annotate:
*With the normal saline group than P＜0.05
*P＜0.01
Conclusion: sharp capsule for treating gastropathy promotes the rat gastric ulcer healing, slight gastric acid inhibitory secretion.Sucralfate promotes ulcer healing, gastric acid inhibitory, pepsinia.
Experiment two: the influence of the rat gastric mucosa injury that sharp capsule for treating gastropathy brings out ethanol.
Grouping and medication: rat is divided into 4 groups (twice) at random, 11 of normal saline groups (NS), and 1 group 11 of sharp capsule for treating gastropathy, 2 groups 8 of sharp capsule for treating gastropathy, sucralfate group (11), per os gives.Administration fasting in the 4th day, the 5th day, be administered once before the experiment, after the administration 1 hour, pour into absolute alcohol 1ml, put to death animal after 1 hour, fixedly the gastric outer wall.
The calculating of damaged area: fixedly after the inside and outside wall 10 minutes, cut off along greater gastric curvature, stomach is flattened, calculate damage index with the Guth method, the damage index standard: 1 is divided into the point-like damage, and 2 are divided into 1mm～2mm damage, and 3 are divided into 3～4mm damage, 4 are divided into 4～5mm damage, and 5 are divided into the damage greater than 5mm.(X ± SD) expression, statistical analysis adopts two sample mean t check to experimental data, P＜0.05 expression significant difference with means standard deviation.
The result: absolute alcohol is strip to gastric mucosal damage more, and slabbing is seldom arranged, and damage is 100% generation, and the matched group damage index is 21.80 ± 5.41, and all the other each medicine groups see Table 3.
The sharp capsule for treating gastropathy of table 3 brings out the influence of rat gastric mucosa injury to ethanol
| Grouping | Quantity (only) | Damage index (X ± SD) | The P value |
| Saline | 11 | 21.80±5.41 | |
| Sharp stomach 1 | 11 | 8.18±3.09 | ＜0.05 |
| Grouping | Quantity (only) | Damage index (X ± SD) | The P value |
| Sharp stomach 2 | 8 * | 19.83±4.04 | ＞0.05 |
| Sucralfate | 11 | 8.33±4.07 | ＜0.05 |
*Annotate: animal example number difference in the table 3,5 is that the result is undesirable because experimental result is found the 376mg/kg group for the first time, thus during compensation, discarded, other group repeated observations several number of animals.
Conclusion: every day, sharp capsule for treating gastropathy, the sucralfate (125mg/kg) of 188mg/kg dosage were resisted absolute alcohol to gastric mucosal damage.
Experiment three: sharp capsule for treating gastropathy brings out the effect of mice stomachache to glacial acetic acid, and animal is divided into 4 groups: the normal saline group, and 1,2 groups of sharp capsule for treating gastropathy, the aspirin group, the sharp capsule for treating gastropathy medication time is the same, but dosage big (3 times, 6 times amounts of people's consumption) a little.Successive administration 4 days, fasting, the 5th day, 1,2 groups of administrations of sharp capsule for treating gastropathy 1 time, aspirin group, oral administration, dosage 200mg/kg.After the administration 1 hour, lumbar injection 0.7% glacial acetic acid 0.1ml/10g body weight.In back 15 minutes of the record injection, animal is turned round the body number of times.
The result: behind the injection glacial acetic acid, hundred-percent animal embodiment occurs turning round and resembles.Matched group on average occurred 29.29 ± 5.6 times in 15 minutes, and it is minimum that the aspirin group reveals, as table 4.1,2 groups of sharp capsule for treating gastropathy, through repeatedly observing, the degree of turning round body is light, has slightly and straightens one's back.When matched group is serious, straighten one's back significantly, lift up tail, stretch hind leg, longer duration.See Table 4.
The sharp capsule for treating gastropathy of table 4 is to the analgesic activity of mice (X ± SD)
| Grouping | The example number | Turn round body number (inferior/15 minute) | The P value |
| Saline | 17 | 29.29±5.6 | |
| Sharp stomach 1 | 16 | 18.33±4.5 | ＜0.05 |
| Sharp stomach 2 | 15 | 16.33±3.6 | ＜0.05 |
| Aspirin | 12 | 6.50±1.3 | ＜0.01 |
Conclusion: sharp capsule for treating gastropathy has slight analgesic effect, and aspirin has good analgesic effect.
Experiment four: sharp capsule for treating gastropathy is to the influence of rat gastric mucosal blood flow.
Medication, dosage and time are as testing 2.The assay method of gastric mucosal blood flow (GMBF) is as follows:
Determining instrument:
1, laser doppler flowmetry (Lascr Dopplcr Flowmctry, LDF), the BPM403A type, U.S. Technical Sourcing Internation produces.
2, PR434 type laser probe.U.S. Technical Sourcing Internation produces.
Assay method: survey GMBF with laser-Doppler (LDF).After 4 days, fasting behind the etherization, is fixed in rat on the platform in administration, is 37 ℃ of thermostats under the platform, to keep rat temperature; In last median abdominal incision 1.5cm, stomach is gently proposed, place 37 ℃ of thermostats, this thermostat connects the constant temperature pump.Temperature with the protection stomach.Pro-greater gastric curvature side is cut one and is about the 0.2cm otch, and miniature laser control head is put into body of stomach from otch, measures GMBF record blood flow curve, continues 1 minute, reads relative value from display, at interval after 5 minutes, and replication 2 times.Its average is as the blood flow of rat glandular stomach body.Experiment same day, matched group after giving normal saline 1ml, 1 hour, under etherization survey GMBF three times, animal is clear-headed immediately, per os gives absolute alcohol 1ml again, surveys GMBF after 1 hour, puts to death animal immediately, checks the gastric mucosa injury situation.The administration group, dispensing 1ml 1 hour afterwards, etherization is surveyed GMBF three times down, irritates absolute alcohol 1ml again, surveys GMBF three times, puts to death animal inspection gastric mucosa injury situation.
The result: the method for measuring GMBF with the laser-Doppler instrument is easy, stable, but replication in a short time.Matched group was 31.95 ± 4.97 (ml/min.100g) before giving ethanol, gives after the ethanol, and be 43.7 ± 3.62 (ml/min.100g).The variation of each group of all the other administrations is as shown in table 5.Ethanol increases GMBF, and blood flow is increased to 43.7 ± 8.09 (ml/min100g) from normal 31.95 ± 4.97 (ml/min.100g), and there were significant differences for both.1 group of sharp capsule for treating gastropathy and normal rat GMBF do not have evident difference, but the rat GMBF that gives ethanol is had the increase effect.As if sucralfate do not influence GMBF.
The sharp capsule for treating gastropathy of table 5 is to the influence of rat gastric mucosal blood flow (X ± SD)
Annotate:
*With normal saline group ratio significant difference P＜0.05 is arranged
*With the matched group of irritating stomach to ethanol significant difference P＜0.05 is arranged relatively.
Conclusion:
1, ethanol increases GMBF.
2, sharp capsule for treating gastropathy (188mg/kg) increases ethanol filling stomach rat GMBF, reduces the gastric mucosa injury that is brought out by ethanol.
3, sharp capsule for treating gastropathy (376mg/kg) increases normal rat GMBF, but the rat GMBF that gives ethanol is reduced, may be relevant with the blood vessel overdistension.
4, sucralfate does not increase the GMBF that ethanol is irritated the stomach rat, but reduces gastric mucosa injury, may also have other mechanism protection gastric mucosas.
Experiment five: sharp capsule for treating gastropathy is to the influence of helicobacter pylorus bacteria growing:
This experiment is got the male ulcer patient's of helicobacter pylori (HP) (through the urease inspection) gastric mucosa and is cultivated with improvement Skirrow culture medium, and under little oxygen condition of 6%, 37 ℃, humidity was cultivated 3-5 days more than 98%.Positive judgement; Translucent linen protuberance, circular petite, diameter 0.52mm, neat in edge, the Gram stained positive, curved or S shape, the sea-gull shape of spreading the wings with reference to the experiment (7) of Tomoyuki, is determined drug concentrations.Medicine dissolution is made into the solution of 10mg/ml in the mute cave liquid of dimethyl.Time spent reuse distilled water diluting becomes needed concentration.Cut-off footpath 6mm circular filter paper sheet, inhaling has the variety classes variable concentrations to hold the survey medicine, is placed on respectively in the agar plate, and 6 filter papers of every kind of concentration inoculation adopt semiquantitative method to judge drug effect.0 is not have bacterial growth around the scraps of paper ,+for the scraps of paper have a few colony growth on every side, ++ for the scraps of paper have a plurality of colony growths on every side, +++be around the scraps of paper intensive colony growth in heaps to be arranged.
The result: as shown in table 6, the result that the concentration of sharp capsule for treating gastropathy shows in 6 wares when 250 μ g/ml is very consistent, around the scraps of paper intensive colony growth in heaps is arranged, and when concentration is 500 μ g/ml, more a plurality of bacterium colonies, (8-12 bacterium colony) is arranged all around 6 scraps of paper.Concentration has several colony growths around the scraps of paper when 1000 μ g/ml, be approximately 4～7.Tripotassium dicitratobismuthate is divided into three concentration, 60 μ g/ml, 120 μ g/ml, 240 μ g/ml, and the situation such as the table 6 of bacterial growth have a few colony growth around the scraps of paper when 240 μ g/ml, but do not suppress fully.See Table 6.
The sharp capsule for treating gastropathy of table 6 is to the inhibitory action of helicobacter pylorus bacteria growing
| Grouping | Concentration (μ g/ml) | The colony growth situation |
| Tripotassium dicitratobismuthate | 60 | +++ |
| 120 | ++ | |
| 240 | + | |
| Sharp capsule for treating gastropathy | 250 | +++ |
| 500 | ++ | |
| 1000 | + |
Conclusion: sharp capsule for treating gastropathy has the effect that suppresses the helicobacter pylorus bacteria growing.
As fully visible, sharp capsule for treating gastropathy can obviously promote the healing of the rat gastric ulcer that acetic acid burns, the opposing absolute alcohol is to gastric mucosal damage, improve the gastric mucosal blood flow of the model mouse of absolute alcohol damage, suppress helicobacter pylori (HP), the slight acetic acid that reduces burns the gastric juice and the gastric acid of ulcer model mouse, and analgesic effect is arranged.Suitably the sharp capsule for treating gastropathy of dosage has the damaging action of protection gastric mucosa opposing ethanol, and the acute inflammation that ethanol is caused has therapeutical effect, to stress having damaged significant protective effect, and is dose-effect relationship.Suitably the sharp capsule for treating gastropathy of dosage has the effect that increases gastric mucosal blood flow.Simultaneously, can also suppress the growth of helicobacter pylori.The effect that these pharmacology indexs point out this medical instrument treatment gastritis to be arranged and alleviate the gastritis symptom.
Show from the toxicologic study aspect in addition:
(1) studies on acute toxicity: the medicated powder suspension of this product is given mouse stomach twice on the one with Cmax, maximum volume, always giving dose is 26.4g/kg (crude drug), be equivalent to the day for human beings 394 times with dosage, observe a week, do not see the reaction of animal dead and overt toxicity, maximum tolerated dose (MTD), the LD50＞26g/kg of this medicine to the mouse stomach administration is described.By the classification of " pharmacology's introduction " book, belong to " actual nontoxic ", by the classification of " new drug evaluation outline " book, belong to " nontoxic substantially ", so clinical application is safe.
(2) long term toxicity research: this product is with 1.7g/kg.d, and 3.4g/kg.d (be equivalent to the clinical consumption of people 25 times, 50 times) gives rat oral gavage, continuous 11 weeks.The ingesting of animal during the administration, drain, activity and hair color be all normal, body weight gain situation and matched group relatively do not have significant difference, 2 week of administration end and drug withdrawal the back blood parameters such as routine blood test regulating liver-QI, the renal function surveyed and main organs coefficient all in normal range, fluctuate, and there is not significant difference with matched group, become celestial all no abnormal change of internal organs of each treated animal of system, histopathologic examination does not all find positive pathology pathological changes.More than test shows after sharp capsule for treating gastropathy is to the animal long term administration there is not cumulative toxicity, and routine blood test and the every index of blood biochemical and internal organs are not all had influence, and long-term oral administration is safe.
Following inventor further specifies technical scheme of the present invention by specific embodiment, but the claimed content of the present invention includes but not limited to these embodiment.
The specific embodiment
Embodiment 1: the preparation of capsule
Prescription: Radix Notoginseng 1500g, Radix Et Rhizoma Rhei (wine is processed) 500g, Alumen (forging) 2000g, Ophicalcitum (forging) 1000g
Method for making: above four flavors, all be ground into fine powder separately, feed intake in proportion with clean powder, mixing sieves, and the dress Capsules goes out 10000, the compacting aluminium foil, packing, promptly.
Embodiment 2: the preparation of tablet
Prescription: Radix Notoginseng 1500g, Radix Et Rhizoma Rhei (wine is processed) 1000g, Alumen (forging) 1000g, Ophicalcitum (forging) 1000g
Method for making: above four flavors, all be ground into fine powder separately, feed intake in proportion with clean powder, and add carboxymethylstach sodium 40g, mixed pelletization, dry granulate adds amount of starch, and mixing is pressed into 10000.
Embodiment 3: the preparation of pill
Prescription: Radix Notoginseng 2500g, Radix Et Rhizoma Rhei (wine is processed) 1000g, Alumen (forging) 1000g, Ophicalcitum (forging) 500g
Method for making: above four flavors, all be ground into fine powder separately, feed intake in proportion with clean powder, and add carboxymethylstach sodium 20g, starch 100g, mixing, the system soft material is pressed into pill.
Embodiment 4: the preparation of powder
Prescription: Radix Notoginseng 2500g, Radix Et Rhizoma Rhei (wine is processed) 500g, Alumen (forging) 2000g, Ophicalcitum (forging) 500g
Method for making: above four flavors, all be ground into fine powder separately, feed intake in proportion with clean powder, mixing, promptly.
Embodiment 5:
Prescription: Radix Notoginseng 1900g, Radix Et Rhizoma Rhei (wine is processed) 700g, Alumen (forging) 1600g, Ophicalcitum (forging) 800g
Method for making: above four flavors, all be ground into fine powder separately, feed intake in proportion with clean powder, mixing, promptly.
Embodiment 6: the capsule to embodiment 1 carries out quality inspection
Differentiate:
(1) get this product, put microscopically and observe, yellow resin canal fragment sees that easily calcium oxalate cluster crystal is big, diameter 60-140um.
(2) get this product content 1g, add dilute hydrochloric acid 15ml, heated and boiled also keeps little and boiled 5 minutes, puts coldly, filters, and gets filtrate 2ml, puts in the test tube, drips ammonia solution to producing white gels shape precipitation, drips alizarine S test solution number droplet, and precipitation becomes cherry red.
(3) get the test liquid under [assay] item, as need testing solution.Other gets Radix Notoginseng control medicinal material powder 0.4g, shines medical material solution in pairs with legal system.Get ginsenoside Rg1, arasaponin R1 reference substance again, add methanol respectively and make the solution that every 1ml contains 1mg, in contrast product solution.According to the thin layer chromatography test, draw each 5ul of above-mentioned solution, put respectively on same silica gel g thin-layer plate, under the condition of relative humidity 45% saturated 30 minutes, the subnatant of placing below 10 ℃ with chloroform-methanol-water (65: 35: 10) is developing solvent, launches, and takes out, dry, spray is with 5% ethanol solution of sulfuric acid, in about 10 minutes of 105 ℃ of bakings, in the test sample chromatograph, with reference substance and the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
(4) get the test liquid under [assay] item, as need testing solution.Other gets Radix Et Rhizoma Rhei control medicinal material powder 0.3g, shines medical material solution in pairs with legal system.According to the thin layer chromatography test, draw above-mentioned two kinds of each 8ul of solution, put respectively on same silica gel g thin-layer plate, upper solution with petroleum ether (30-60 ℃)-formic acid second fat-formic acid (15: 5: 1) is developing solvent, launches, and takes out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show 5 identical orange-yellow fluorescence speckles; Put in the ammonia smoked after, speckle becomes orange red.
Assay:
Get the about 1g of this product content, the accurate title, decide, and puts in the tool plug triangular flask, accurate methanol 10ml, the close plug of adding, claim decide weight, supersound extraction 1 hour is put coldly, and weight decided in title, supplies the weight that subtracts mistake with methanol, shake up, put in the centrifuge tube, after the centrifugalize, get supernatant, as need testing solution.Other gets the ginsenoside Rg1 reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography, draw above-mentioned two kinds of each 5ul of solution, the cross point is on same silica gel g thin-layer plate respectively, (20: 40: 10: 20) lower floor's solution of 5-10 ℃ of placement was developing solvent with chloroform-n-butyl alcohol-methanol-water, after under relative humidity 45% condition saturated 20 minutes, launch, take out, dry, spray is with 5% ethanol solution of sulfuric acid, about 10 minutes of 105 ℃ of bakings, clear to the speckle colour developing, take out, on lamellae, cover onesize glass plate, use immobilization with adhesive tape on every side, scan wavelength according to thin layer chromatography (an appendix VIB of Chinese Pharmacopoeia nineteen ninety-five version thin layer chromatography scanning): λ S=525nm, λ R=700nm, measure test sample trap integrated value and reference substance trap integrated value, calculate, promptly.Every of this product contains ginsenoside Rg1 and is no less than 4.0mg.
Claims (10)
1. a Chinese medicine composition that is used for the treatment of gastropathy is characterized in that this Chinese medicine composition is to be made by the crude drug of following weight ratio: 15～25 parts of Radix Notoginseng, 5～10 parts of Radix et Rhizoma Rhei (processed with wine), 10～20 parts of calcined Alumen, 5～10 parts of calcined OPHICALCITUMs.
2. Chinese medicine composition as claimed in claim 1 is characterized in that the proportioning of each crude drug is: 17～20 parts of Radix Notoginseng, 5～8 parts of Radix et Rhizoma Rhei (processed with wine), 15～18 parts of calcined Alumen, 7～9 parts of calcined OPHICALCITUMs.
3. Chinese medicine composition as claimed in claim 2 is characterized in that the proportioning of each crude drug is: 19 parts of Radix Notoginseng, 7 parts of Radix et Rhizoma Rhei (processed with wine), 16 parts of calcined Alumen, 8 parts of calcined OPHICALCITUMs.
4. as claim 1,2 or 3 described Chinese medicine compositions, it is characterized in that this Chinese medicine composition is made into any in tablet, capsule, pill, the powder.
5. the method for preparing Chinese medicine composition as claimed in claim 4 is characterized in that each crude drug pulverize separately is become fine powder, feeds intake with clean medicated powder in proportion, and according to the suitable adjuvant of needs adding of dosage form, technology is made required dosage form routinely.
6. as the detection method of Chinese medicine composition as described in the claim 4, this method contains qualitative identification and assay two parts, it is characterized in that containing in the qualitative identification following one or several:
A, get the product powder, put microscopically and observe, yellow resin canal fragment sees that easily calcium oxalate cluster crystal is big, diameter 60-140um;
B, get product powder 1～3g, add dilute hydrochloric acid 15ml, heated and boiled also keeps little and boiled 5 minutes, puts coldly, filters, and gets filtrate 2ml, puts in the test tube, drips ammonia solution to producing white gels shape precipitation, drips alizarine S test solution number droplet, and precipitation becomes cherry red;
C, get product powder 1～3g, put in the tool plug triangular flask, add methanol 10ml, supersound extraction 1 hour is filtered, and gets filtrate as need testing solution; Other gets Radix Notoginseng control medicinal material powder 0.4g, shines medical material solution in pairs with legal system; Get ginsenoside Rg1, arasaponin R1 reference substance again, add methanol respectively and make the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw each 5ul of above-mentioned solution, put respectively on same silica gel g thin-layer plate, under the condition of relative humidity 45% saturated 30 minutes, with volume ratio is that the subnatant that chloroform-methanol-water mixed liquid of 65: 35: 10 is placed below 10 ℃ is developing solvent, launches, and takes out, dry, spray is with 5% ethanol solution of sulfuric acid, in about 10 minutes of 105 ℃ of bakings, in the test sample chromatograph, with reference substance and the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
D, get product powder 1～3g, put in the tool plug triangular flask, add methanol 10ml, supersound extraction 1 hour is filtered, and gets filtrate as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material powder 0.3g, shines medical material solution in pairs with legal system; According to the thin layer chromatography test, draw above-mentioned two kinds of each 8ul of solution, put respectively on same silica gel g thin-layer plate, with volume ratio is that the upper solution of 15: 5: 1 petroleum ether-formic acid second fat-formic acid mixed liquors is developing solvent, launches, and takes out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show 5 identical orange-yellow fluorescence speckles; Put in the ammonia smoked after, speckle becomes orange red.
7. the quality determining method of Chinese medicine composition as claimed in claim 6 is characterized in that content assaying method wherein realizes in the following way: get product powder 1～2g, accurate claim fixed, put in the tool plug triangular flask accurate methanol 10ml, the close plug of adding, claim to decide weight, supersound extraction 1 hour is put cold, claim to decide weight, supply the weight that subtracts mistake, shake up with methanol, put in the centrifuge tube, after the centrifugalize, get supernatant, as need testing solution; Other gets the ginsenoside Rg1 reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography, draw above-mentioned two kinds of each 5ul of solution, the cross point is on same silica gel g thin-layer plate respectively, with volume ratio is 20: 40: 10: lower floor's solution of chloroform-n-butyl alcohol of 20-methanol-water mixture 5-10 ℃ placement is developing solvent, after under relative humidity 45% condition saturated 20 minutes, launch, take out, dry, spray is with 5% ethanol solution of sulfuric acid, about 10 minutes of 105 ℃ of bakings, clear to the speckle colour developing, take out, on lamellae, cover onesize glass plate, fixing, scan wavelength according to thin layer chromatography: λ S=525nm, λ R=700nm, measure test sample trap integrated value and reference substance trap integrated value, calculate, promptly get the content of ginsenoside Rg1 in the product.
8. be used for the treatment of application in the medicine of gastropathy as arbitrary described Chinese medicine composition in the claim 1 to 3 in preparation.
9. be used for the treatment of application in the medicine of gastritis and/or stomachache and/or gastric acid as arbitrary described Chinese medicine composition in the claim 1 to 3 in preparation.
10. be used for the treatment of application in the medicine of erosive gastritis as arbitrary described Chinese medicine composition in the claim 1 to 3 in preparation.
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