CN102716169B - Application of common vladimiria root or extract of common vladimiria root in preparing medicines for treating chronic atrophic gastritis - Google Patents
Application of common vladimiria root or extract of common vladimiria root in preparing medicines for treating chronic atrophic gastritis Download PDFInfo
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Abstract
The invention provides application of common vladimiria root or extract of the common vladimiria root in preparing medicines for treating chronic atrophic gastritis and novel application of a medicine composition formed by compatibility of the common vladimiria root or the extract of the common vladimiria root and hippophae rhamnoides or hippophae rhamnoides oil extractive. The common vladimiria root or the extract of the common vladimiria root can promote intestinal peristalsis, restrains contraction effect on smooth muscle caused by acetylcholine, avoids or reduces gland contraction and inflammatory cell infiltration, namely can obviously improve gastrointestinal motility and pathological symptoms of chronic atrophic gastritis, and has good treating effect on the chronic atrophic gastritis caused by autoimmunity or/and bile regurgitation. Simultaneously, the compatibility of the common vladimiria root and hippophae rhamnoides gives play to the synergy effect, the effect in treating the chronic atrophic gastritis is obvious, and the application is a new choice for clinical medication.
Description
Technical field
The present invention relates to the new purposes of Radix Vladimiriae or its extract.
Background technology
Chronic atrophic gastritis (Chronic Atrophic Gastritis, CAG) be digestive system commonly encountered diseases and difficult disease, it is the important front disease (annual canceration rate is 0.5%~1%) of gastric cancer, pathologic finding gastric mucosa atrophy attenuation, body of gland composition reduce or disappear, clinical manifestation is gastral cavilty distension or distending pain, heating installation, noisy, inappetence, becomes thin etc., belongs to the disease categories such as Chinese medicine feeling of fullness, noisy, stomachache.What all think for a long time chronic atrophic gastritis is the result of many factors comprehensive function, as helicobacter pylori infections, peptic ulcer, and it also changes with its activeness and difficulty is more relevant repeatedly, relevant to infecting the factors such as reactivity, bile reflux, autoimmune, heredity, age, high salt and low vitamin diet with environmental factors, host in addition.[National Drug Administration. new Chinese medicine guideline of clinical investigations: tentative. Beijing: the Chinese Medicine science and technology .2002:124-129 of publishing house; The spleen-stomach disease branch of China Association of Traditional Chinese Medicine. chronic atrophic gastritis Chinese traditional medical diagnose National Consensus (2009, Shenzhen). the Chinese combination of Chinese and Western medicine digestion magazine .2010,18(5): 345-349]
Current, doctor trained in Western medicine mainly adopts and removes helicobacter pylori (HP), protection gastric mucosa, strengthens the treatment processing such as gastric motility, but doctor trained in Western medicine is unsatisfactory to the curative effect of chronic atrophic gastritis, does not also find the specific drug for this disease; And Chinese medicine, Tibetan medicine and pharmacology can improve clinical symptoms, alleviate mucosa infection, play a role by strengthening gastric mucosal protection function, even can stop the generation of CAG canceration, untoward reaction is relatively little, there is the curative effect of consolidation, prevent the comprehensive functions such as recurrence and whole body adjustment, in the treatment of chronic atrophic gastritis, have obvious advantage [Yang Liqiong. the progress of therapy of combining Chinese and Western medicine chronic atrophic gastritis. medical information .2010,23(8): 2689; More hide and add, Ga Zang arranges, Wei Gang. and Tibetan medicine treats chronic atrophic gastritis 76 examples. the modern combination of Chinese and Western medicine magazine .2010,19(22): 2810].Therefore, the medicine of exploitation treatment chronic atrophic gastritis from Chinese medicine, national medicine, seems particularly necessary.
Radix Vladimiriae is the dry root of Compositae Dolomiaea plant Radix Vladimiriae Vladimiria souliei (Franch.) Ling. and gray wool Radix Vladimiriae Vladimiria souliei (Franch.) Ling var.cinerea Ling., nature and flavor acrid, bitter, warm, function promoting the circulation of QI to relieve pain, be used for the treatment of the disease such as abdominal distention, liver and gall pain [Chinese Pharmacopoeia Commission. one of Pharmacopoeia of People's Republic of China version in 2005. Beijing: the .2005:41 of Chemical Industry Press], be one of common medicine for the treatment of digestive tract disease.Radix Vladimiriae be in, hide intersect medicine variety, all on the books in the classical masterpiece Four-Volume Medical Code of Tibetan medicine, " Jingzhubencao ", clear " Baconic " heat of function, blood-activating analgetic, spleen invigorating removing food stagnancy, control the disease such as stomach abdominal distention and pain, hypochondriac pain due to " Baconic " heat symptom-complex, QI and blood amount discord [Luo Dashang chief editor. book on Chinese herbal medicine is hidden by China. Beijing: Nationalities Press, 1997.265; Institute for drug control, Qinghai Province, the chief editor of Qinghai Tibet Medical Institute. Shanghai: Shanghai science tech publishing house, 1996, volume Two .120].Number of patent application: disclose the purposes of Radix Vladimiriae for peptic ulcer control in 200710202833.6.The patent No.: can be used for treating Peptic Ulcers after disclosing Radix Vladimiriae extract and Oleum Hippophae extract compatibility in 200610020203.2.Peptic ulcer, as one of numerous predisposing factorss of chronic atrophic gastritis, the in the situation that of its long-term pessimal stimulation or faulty union, may increase the incidence probability of chronic atrophic gastritis, but between the two, there is no necessary connection, and peptic ulcer is mainly non-atrophic acute stage disease (taking ulcer as main, body of gland is complete), there were significant differences (taking cellular infiltration as main, body of gland is impaired) with chronic atrophic gastritis.
At present, yet there are no alone Radix Vladimiriae or will treat the relevant report of chronic atrophic gastritis after Radix Vladimiriae extract and Oleum Hippophae extract compatibility.
Summary of the invention
Technical scheme of the present invention has been to provide the new purposes of Radix Vladimiriae or its extract.Another technical scheme of the present invention has been to provide the new purposes of the pharmaceutical composition after Radix Vladimiriae or its extract and Fructus Hippophae or Oleum Hippophae extract compatibility.
The invention provides Radix Vladimiriae or its extract purposes in the medicine of preparation treatment chronic atrophic gastritis.
Further, described medicine is promotion enterokinesia, improves duodenum smooth muscle contraction ability, treatment autoimmune or/and the medicine of the chronic atrophic gastritis due to bile reflux.
Further, in described Radix Vladimiriae extract total lactone content in dehydrocostuslactone more than 50%w/w.
Wherein, the preparation method of described Radix Vladimiriae extract is:
Get Radix Vladimiriae and be ground into coarse powder, adopt supercritical extraction or solvent supersonic extraction or the extraction of solvent percolation or solvent refluxing to extract any extracting method, collect Radix Vladimiriae extract.
Further, the concrete operations of described supercritical extraction are as follows: Radix Vladimiriae is ground into after coarse powder, adopts supercritical fluid carbon dioxide to extract, separate, after 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract;
The concrete operations that described solvent supersonic extracts are as follows: Radix Vladimiriae is ground into after coarse powder, add concentration to be not less than 75% ethanol, after infiltration, supersound extract, 60 DEG C of following decompression and solvent recoveries, then extract with water-ethyl acetate system, collect ethyl acetate layer, 60 DEG C of following reclaim under reduced pressure ethyl acetate, 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract;
The concrete operations that described solvent percolation extracts are as follows: Radix Vladimiriae is ground into after coarse powder, add concentration to be not less than 75% ethanol, after infiltration, percolation extracts, 60 DEG C of following decompression and solvent recoveries, then extract with water-ethyl acetate system, collect ethyl acetate layer, 60 DEG C of following reclaim under reduced pressure ethyl acetate, 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract;
The concrete operations that described solvent refluxing extracts are as follows: Radix Vladimiriae is ground into after coarse powder, add concentration to be not less than 75% ethanol, after infiltration, reflux, extract, 2 ~ 3 times, each 1 ~ 2 hour, merge extractive liquid,, 60 DEG C of following decompression and solvent recoveries, then extract with water-ethyl acetate system, collect ethyl acetate layer, 60 DEG C of following reclaim under reduced pressure ethyl acetate, 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract.
The present invention also provides the purposes of the pharmaceutical composition being prepared from as the crude drug of following weight proportion in the medicine of preparation treatment chronic atrophic gastritis:
1~9 part of Radix Vladimiriae, 1~9 part of Fructus Hippophae.
Further, described medicine is the preparation being prepared from by the raw material of following weight proportioning:
3 parts of Radix Vladimiriaes, 1.5 parts of Fructus Hippophaes.
The present invention also provides the purposes of the pharmaceutical composition being prepared from as the crude drug of following weight proportion in the medicine of preparation treatment chronic atrophic gastritis:
18~54 parts of Radix Vladimiriae extracts, 15~90 parts of Oleum Hippophae extracts.
Further, described medicine is the preparation being prepared from by the raw material of following weight proportioning:
18 parts of Radix Vladimiriae extracts, 15 parts of Oleum Hippophae extracts.
Wherein, in described Radix Vladimiriae extract total lactone content in dehydrocostuslactone more than 50%w/w; In described Oleum Hippophae extract containing ester amount in linoleic acid triglyceride more than 50%w/w.
Further, the preparation method of described Oleum Hippophae extract is as follows:
Get the mixture of sea buckthorn fruit, seed or fruit and seed and pulverize, extract by solvent method reflux, extract,, supercritical extraction or any method of squeezing centrifuging, collect Oleum Hippophae extract.
Further, described solvent method reflux, extract, is after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, solvent method reflux, extract,, and by normal heptane, heating and refluxing extraction 2 times, each 4 hours, reclaim solvent, obtain Oleum Hippophae extract;
Described supercritical extraction is after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, supercritical CO
2fluid extraction, collects Oleum Hippophae extract through primary separator, and wherein, extracting pressure is 40MPa, and extraction temperature is 65 DEG C, and extraction flow is 18L/h, and flash trapping stage pressure is 6.5MPa, and flash trapping stage temperature is 36 DEG C, obtains Oleum Hippophae extract;
Described squeezing centrifuging is that after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, squeezing centrifuging is extracted, and adopts after mechanical expression, obtains slightly oil of Fructus Hippophae, and centrifuging separates, and obtains Oleum Hippophae extract.
Radix Vladimiriae of the present invention or its extract can promote enterokinesia, suppress the contraction of acetylcholine to smooth muscle, avoid or reduce body of gland atrophy and inflammatory cell infiltration, show that Radix Vladimiriae or its extract can obviously improve gastrointestinal motility and the pathological symptom of chronic atrophic gastritis, especially for autoimmune or/and the chronic atrophic gastritis due to bile reflux has good therapeutical effect; Meanwhile, the present invention, by after Radix Vladimiriae and the use of Fructus Hippophae compatibility, has brought into play synergistic function, and treatment chronic atrophic gastritis effect is more obvious, for clinical application provides new selection.
Detailed description of the invention
The preparation method of embodiment 1 Radix Vladimiriae extract
Get Radix Vladimiriae and be ground into coarse powder, adopt supercritical extraction or solvent supersonic extraction or the extraction of solvent percolation or solvent refluxing to extract any extracting method, collect Radix Vladimiriae extract.
A, Radix Vladimiriae is ground into after coarse powder, adopts supercritical fluid carbon dioxide to extract, separate, after 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract;
The concrete operations that b, described solvent supersonic extract are as follows: Radix Vladimiriae is ground into after coarse powder, add concentration to be not less than 85% ethanol, after infiltration, supersound extract, 60 DEG C of following decompression and solvent recoveries, then extract with water-ethyl acetate system, collect ethyl acetate layer, 60 DEG C of following reclaim under reduced pressure ethyl acetate, 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract;
The concrete operations that c, described solvent percolation extract are as follows: Radix Vladimiriae is ground into after coarse powder, add concentration to be not less than 85% ethanol, after infiltration, percolation extracts, 60 DEG C of following decompression and solvent recoveries, then extract with water-ethyl acetate system, collect ethyl acetate layer, 60 DEG C of following reclaim under reduced pressure ethyl acetate, 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract;
The concrete operations that d, described solvent refluxing extract are as follows: Radix Vladimiriae is ground into after coarse powder, add concentration to be not less than 85% ethanol, after infiltration, reflux, extract, 2 ~ 3 times, each 1 ~ 2 hour, merge extractive liquid,, 60 DEG C of following decompression and solvent recoveries, then extract with water-ethyl acetate system, collect ethyl acetate layer, 60 DEG C of following reclaim under reduced pressure ethyl acetate, 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract.
According to Chinese patent: in 200610020203.2, the method for quality control of embodiment 8 carries out assay to Oleum Hippophae extract, and it the results are shown in following table:
Table 1
Above result shows, the extraction efficiency of above-mentioned 4 kinds of methods is close.Said extracted method can be referring to Chinese patent: embodiment 1 in 200610020203.2.
The preparation method of embodiment 2 Oleum Hippophae extracts
Get the mixture of sea buckthorn fruit, seed or fruit and seed and pulverize, extract by solvent method reflux, extract,, supercritical extraction or any method of squeezing centrifuging, collect Oleum Hippophae extract.
Method one: described solvent method reflux, extract, is after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, solvent method reflux, extract,, by normal heptane, heating and refluxing extraction 2 times, each 4 hours, reclaim solvent, obtain Oleum Hippophae extract;
Method two: described supercritical extraction is after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, supercritical CO
2fluid extraction, collects Oleum Hippophae extract through primary separator, and wherein, extracting pressure is 40MPa, and extraction temperature is 65 DEG C, and extraction flow is 18L/h, and flash trapping stage pressure is 6.5MPa, and flash trapping stage temperature is 36 DEG C, obtains Oleum Hippophae extract;
Method three: described squeezing centrifuging is that after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, squeezing centrifuging is extracted, and adopts after mechanical expression, obtains slightly oil of Fructus Hippophae, and centrifuging separates, and obtains Oleum Hippophae extract.
According to Chinese patent: in 200610020203.2, the method for quality control of embodiment 9 carries out assay to Oleum Hippophae extract, and it the results are shown in following table:
Table 2
Said extracted method can be referring to Chinese patent: embodiment 2 in 200610020203.2.By test example, beneficial effect of the present invention is described below.
The Pharmacodynamics screening test of the each medicine of test example 1 the present invention to chronic atrophic gastritis
One, the preparation of tested medicine
Radix Vladimiriae extract: according to the extracting method d preparation of embodiment 1, then add PEG-4000 and make the solution of every 1ml containing 0.5g primary crude drug, for subsequent use.Be 3~9g/60kg by middle regulation Radix Vladimiriae primary crude drug Coming-of-Age Day consumption of Chinese Pharmacopoeia version in 2010, mice consumption is converted by 60 times of adult's consumption, i.e. 3~9g/kg; In Radix Vladimiriae, the content of Radix Vladimiriae extract is about 6%, and Radix Vladimiriae extract mice consumption is 0.18~0.54g/kg.
Oleum Hippophae extract: prepare according to the extracting method of embodiment 2 three.Be 3~9g/60kg by middle regulation Fructus Hippophae primary crude drug Coming-of-Age Day consumption of Chinese Pharmacopoeia version in 2010, mice consumption is converted by 60 times of adult's consumption, i.e. 3~9g/kg; In Fructus Hippophae, the content of Oleum Hippophae extract is about 10%, and Oleum Hippophae extract mice consumption is 0.15~0.9g/kg.
Two, experimental technique and result
1. laboratory animal: SD rat, male and female half and half, body weight 180g
2. experimental technique:
2.1 model group
Adopt the integrated approach that simultaneously carries out active immunity and bile and hot water gavage, make rat atrophic gastritis model.(1) active immunity: every rat skin lower injection adjuvant antigen (with the tissue homogenate of the normal saline of gastric mucosa of rat of the same race and the Emulsion that Freuud adjuvant is made into 1:1) 0.3ml, duplicate injection 1 time after 1 month.(2) bile gavage: in doing active immunity, adopt the bile without suppurative inflammation patient's drain, by 12.5ml/kg to rat oral gavage (gavage is stopped eating for first 4 hours, freely drinks water), every day 1 time, continuous 70 days.(3) hot water gavage: in (with bile gavage interval 5 hours) on the same day by bile gavage, with 50 DEG C of hot water 12.5ml/kg gavages, every day 1 time, continuous 7O days.
2.2 normal group
Normal saline 12.5ml/kg gavage, every day 2 times (with model group gavage time synchronized), continuous 70 days.
2.3 administration groups and positive drug administration group
Get model group rat, random packet, by uniform Design dosage gavage every day 1 time, continuous 60 days.
Each treated animal is conventional raises, and after administration finishes, carries out histopathologic examination, observes therapeutic outcome.
Table 3 factor level table
Table 4 screening test table and result table
Relatively be utmost point significant difference (P<0.01) with model group, with positive group relatively there are no significant difference (P>0.05)
Below respectively organize the symptom tool of each group of pathologic finding data declaration to chronic atrophic gastritis and be significantly improved effect.
Adopt data analysis software to carry out quadratic polynomial stepwise regression analysis to data:
Y=197.5-773.6*X1-13.3*X2+1118.8*X1*X1
Regression equation meaningful (P=0.0558), wherein X1 is utmost point appreciable impact factor (P=0.0073), and X1*X1 is utmost point appreciable impact factor (P=0.0063), and X2 is non-appreciable impact factor (P=0.2753).
Optimality analysis result to influence factor shows: when X1 value is 0.18, X2 value is while being 0.15, regression equation is obtained maximum, when conversion is Radix Vladimiriae 3g/kg, Fructus Hippophae 1.5g/kg for medical material consumption, to improvement effect the best of chronic atrophic gastritis.
Pathological observation conclusion:
Rats in normal control group stomach is less, and coat of the stomach elasticity is good, and pleat smooth surface and regular has more mucus, and mucosa pinkiness is glossy, and without petechia, under mucosa, blood vessel is not obvious.Microscopic observation gastric mucosa thickness is large, and epithelium is complete, epithelial cell marshalling, and nothing comes off or is damaged, and cell is monolayer column, and glandular epithelium and glandular tube boundary are clear, lamina propria body of gland regular shape.
The attenuation of model group gastric wall in rats, poor flexibility, gastric content increases, and pleat is low flat, moves towards disorderly, disappears compared with multizone especially gastric antrum portion pleat, and mucus is few, and mucosa color and luster is greyish white, is dispersed in as seen petechia, and under mucosa, blood vessel is high-visible.The attenuation of Microscopic observation gastric mucosa layer, imperfect, visible degeneration in various degree or downright bad exfoliative cyte, body of gland is atrophy or disappearance in various degree, and interstitial has multiple inflammatory cell (being mainly lymphocyte and plasma cell) to infiltrate.
Administration group epithelial cell is relatively complete, and cellular morphology is normal, and body of gland is arranged and slightly owed regular.Flesh layer progressive additive, thickness is more even.Top layer mucosa is without coming off, and body of gland is without obvious atrophy; In gastric antrum portion, glandular stomach and stomach intersection lamina propria, cell infiltration significantly reduces.Lamina propria edema, vasodilation improve compared with model group.
From above-mentioned experiment, find out, Radix Vladimiriae extract, Oleum Hippophae extract use separately all has certain improvement effect to the relevant symptoms of chronic atrophic gastritis due to bile reflux, after the two compatibility, most experiments has all embodied the effect that is better than single medicine, illustrates after both compatibilities and has certain synergistic function; And in regression equation, two medicines are introduced as influence factor, and certain synergistic function is described.
The impact of test example 2 Radix Vladimiriae extracts on enterokinesia and duodenum smooth muscle
Chronic Atrophic Gastritis Patients, have certain stomach-pylorus-uodenal movement obstacle, this is also one of reveal any symptoms after body of gland atrophy, therefore, the adjusting of medicine to enterokinesia, duodenum smooth muscle movement ability, can play certain improvement effect to the symptom of chronic atrophic gastritis.By effect experiment, the impact of Radix Vladimiriae extract on enterokinesia, duodenum smooth muscle is described below.
1. experiment material
1.1. laboratory animal
Mice: Kunming kind, Chengdu University of Traditional Chinese Medicine's Experimental Animal Center, the laboratory animal quality certification number: the real moving pipe o.11 in river.
Rabbit: the large ear of Japan is white, is provided the laboratory animal quality certification number: SCXK(river 2004-15 by Sichuan Academy of Medical Sciences's Experimental Animal Center).
1.2. the preparation of medicinal liquid
Get Radix Vladimiriae medical material Vladimiria souliei (Franch.) Ling var.cinerea Ling, make extractum with 75% ethanol percolation, extract with ethyl acetate, obtain Ethyl acetate extract.Known through extractant method optimization experiment, ethanol extract after ethyl acetate extraction, the effectively total lactone of enrichment Radix Vladimiriae.
1.3. experimental drug
Motilium (batch number: C50126127, the accurate font size of traditional Chinese medicines: H10910003, manufacturer: Xian-Janssen Pharmaceutical Ltd.); Pethidine (5%, product batch number 690101); (lot number is acecoline: 0000420); Atropine sulfate injection (Xuzhou Lai En pharmaceutcal corporation, Ltd, lot number: 011020); Tyrode's solution; Sodium chloride (Jiao Jian group chemical reagent factory, lot number: 20000706); Potassium chloride (Chengdu chemical reagent factory, lot number: 990928); Magnesium sulfate (MgSO
47H
2o, 20040902), sodium dihydrogen phosphate (Kingsoft, Chengdu chemical reagent factory, lot number: 20001011), sodium bicarbonate (upper marine rainbow photoinitiator chemical factory, lot number: 010421) Chengdu Ke Long chemical reagent factory, lot number:; Calcium chloride (Deng Zhong chemical plant, Tianjin City Tanggu, lot number: 20000106); Glucose (Sichuan Fei Deli pharmaceutical Co. Ltd, lot number: 040901); Aspirin effervescent tablets (product batch number: 0407002); Glacial acetic acid (Chengdu Hong He chemical reagent factory, lot number: 030405).
1.4 experimental apparatus
Magnus' bath (50ml type); BL-410 microcomputer type biological signal collecting and processing system (Chengdu TME Technology Co., Ltd.); Physiological pressure transducer (YH-4 type, Beijing Astronautics Medical Engineering Inst.); YLS-6A intelligence hot-plate instrument (Shandong Academy of Medical Sciences's equipment station).
2. experimental technique and result
The impact of the each extract of 2.1 Radix Vladimiriae on mice enterokinesia
Get 120 of white mice, male and female half and half, laboratory rearing 3 days, be divided at random 13 groups, every group 10, water 24h is can't help in fasting, gavage gives respective concentration medicine group 3 days continuously, after last administration 30min, gavage carbon powder suspension (10% active carbon, 10% arabic gum) 0.2mL/ is only, after 20min, put to death, open abdominal cavity, separate mesentery, clip upper end is to pylorus, the intestinal pipe of lower end to ileocecum portion, be placed on glass, gently that small intestinal is stretching, measure Length of intestine as " small intestinal total length " taking ruler, distance from pylorus to carbon powder forward position is " carbon powder is at the advance distance of enteral ", calculate carbon powder ink propulsive rate (carbon powder ink propulsive rate (%)=carbon powder advance distance (cm)/small intestinal total length (cm) × 100%.The results are shown in following table.
The impact of table 5 Radix Vladimiriae extract on mice enterokinesia
Note: * and the comparison of blank group, P<0.05; * and the comparison of blank group, P<0.01
Result shows: motilium group can obviously promote enterokinesia (P < 0.01), and ethyl acetate high dose group can obviously promote enterokinesia (P < 0.05).
The impact that the each extract of 2.2 Radix Vladimiriae strengthens duodenum in rabbit smooth muscle contraction ability due to acetylcholine
Adjust Magnus' bath, oxygen generator, pressure transducer and BL-410 microcomputer type biological signal collecting and processing system, make normal work, return to zero and calibrate.Get rabbit (fasting 12h before experiment), hitting occipital bone with wooden mallet puts to death, cut immediately abdominal cavity open, take out one section of duodenum, be placed in the beaker that fills tyrode's solution, fall mesentery along intestinal wall simple separation, and intestinal contents is rinsed well with tyrode's solution, intestinal tube is cut into the intestinal segment of 1.5-2.5cm, first observes the motion of normal myenteron; Adjust myenteron tension force in Magnus' bath, the contracting that makes to relax is stablized after 10-30min, trace the curve of one section of myenteron proper motion then, in Magnus' bath, drip various medicinal liquids (seeing below) again, the immediate record contracting curve that relaxes (drips at every turn and all applies tyrode's solution before medicinal liquid and rinse myenteron 2-3 time, fresh body lotion can stop 1~2min and then bleed off, and returns to before medication and adds lower group of medicinal liquid after level again wait the contracting of relaxing).
The order of administration of acetylcholine modeling: can complete following experiment on a myenteron.Observe the effect of Radix Vladimiriae extract solution: 1. record normal value; 2. after 60s, add acetylcholine solution 25 μ l; 3. after 30s, add Radix Vladimiriae to extract solution 100 μ l; 4. after 30s, add again Radix Vladimiriae to extract solution 100 μ l; 5. after 30s, add again Radix Vladimiriae to extract solution 100 μ l; Rinse myenteron 2~3 times with tyrode's solution, fresh body lotion can stop 1~2min and then bleed off, and returns to before medication and adds lower group of medicinal liquid after level again wait the contracting of relaxing.Observe atropinic effect (because atropinic inhibitory action is too strong, so the experiment of putting behind): 9. record normal value; 10. after 60s, add acetylcholine solution 25 μ l; (11) after 30s, add atropine 25 μ l; Rinse myenteron 2~3 times with tyrode's solution, fresh body lotion can stop 1~2min and then bleed off, and returns to before medication and adds lower group of medicinal liquid after level again wait the contracting of relaxing.Experimental result sees the following form.
The impact that table 6 Radix Vladimiriae extract strengthens duodenum in rabbit smooth muscle contraction ability due to acetylcholine
Group | Sample | Drug dose (mg/ml) | Mean tension |
Acetylcholine-normal | 10 | / | 3.63±2.31 |
Atropine-normal | 10 | 0.00025 | -0.94±0.74** |
Ethyl acetate high dose group-normal | 10 | 0.2415 | 1.73±1.23* |
Ethyl acetate low dose group-normal | 10 | 0.0805 | 2.46±1.38 |
Note: * and the comparison of blank group, P<0.05; * and the comparison of blank group, P<0.01.
Result shows, atropine group can obviously suppress the contraction (P<0.01) of acetylcholine to smooth muscle, and ethyl acetate high dose group can obviously suppress the contraction (P < 0.05) of acetylcholine to smooth muscle.
In sum, Radix Vladimiriae of the present invention or its extract can promote enterokinesia, suppress the contraction of acetylcholine to smooth muscle, avoid or reduce body of gland atrophy and inflammatory cell infiltration, show that Radix Vladimiriae or its extract can obviously improve gastrointestinal motility and the pathological symptom of chronic atrophic gastritis, especially for autoimmune or/and the chronic atrophic gastritis due to bile reflux has good therapeutical effect; Meanwhile, the present invention, by after Radix Vladimiriae and the use of Fructus Hippophae compatibility, has brought into play synergistic function, and treatment chronic atrophic gastritis effect is more obvious, for clinical application provides new selection.
Claims (8)
- Radix Vladimiriae or its extract as unique active component the purposes in the medicine of preparation treatment chronic atrophic gastritis; In described Radix Vladimiriae extract total lactone content in dehydrocostuslactone more than 50%w/w.
- 2. purposes according to claim 1, is characterized in that: described medicine is to promote enterokinesia, improve duodenum smooth muscle contraction ability or treat autoimmune or/and the medicine of the chronic atrophic gastritis due to bile reflux.
- 3. purposes according to claim 1 and 2, is characterized in that: the preparation method of described Radix Vladimiriae extract is:Get Radix Vladimiriae and be ground into coarse powder, adopt supercritical extraction or solvent supersonic extraction or the extraction of solvent percolation or solvent refluxing to extract any extracting method, collect Radix Vladimiriae extract.
- 4. purposes according to claim 3, it is characterized in that: the concrete operations of described supercritical extraction are as follows: Radix Vladimiriae is ground into after coarse powder, adopt supercritical fluid carbon dioxide to extract, separate, after 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract;The concrete operations that described solvent supersonic extracts are as follows: Radix Vladimiriae is ground into after coarse powder, add concentration to be not less than 75% ethanol, after infiltration, supersound extract, 60 DEG C of following decompression and solvent recoveries, then extract with water-ethyl acetate system, collect ethyl acetate layer, 60 DEG C of following reclaim under reduced pressure ethyl acetate, 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract;The concrete operations that described solvent percolation extracts are as follows: Radix Vladimiriae is ground into after coarse powder, add concentration to be not less than 75% ethanol, after infiltration, percolation extracts, 60 DEG C of following decompression and solvent recoveries, then extract with water-ethyl acetate system, collect ethyl acetate layer, 60 DEG C of following reclaim under reduced pressure ethyl acetate, 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract;The concrete operations that described solvent refluxing extracts are as follows: Radix Vladimiriae is ground into after coarse powder, add concentration to be not less than 75% ethanol, after infiltration, reflux, extract, 2 ~ 3 times, each 1 ~ 2 hour, merge extractive liquid,, 60 DEG C of following decompression and solvent recoveries, then extract with water-ethyl acetate system, collect ethyl acetate layer, 60 DEG C of following reclaim under reduced pressure ethyl acetate, 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract.
- 5. as the purposes of the pharmaceutical composition that is prepared from of the crude drug of following weight proportion in the medicine of preparation treatment chronic atrophic gastritis:3 parts of Radix Vladimiriaes, 1.5 parts of Fructus Hippophaes;In crude drug, the extracting method of Radix Vladimiriae is:Get Radix Vladimiriae and be ground into coarse powder, adopt supercritical extraction or solvent supersonic extraction or the extraction of solvent percolation or solvent refluxing to extract any extracting method, collect Radix Vladimiriae extract;Wherein, the concrete operations of described supercritical extraction are as follows: Radix Vladimiriae is ground into after coarse powder, adopts supercritical fluid carbon dioxide to extract, separate, after 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract; The concrete operations that described solvent supersonic extracts are as follows: Radix Vladimiriae is ground into after coarse powder, add concentration to be not less than 75% ethanol, after infiltration, supersound extract, 60 DEG C of following decompression and solvent recoveries, then extract with water-ethyl acetate system, collect ethyl acetate layer, 60 DEG C of following reclaim under reduced pressure ethyl acetate, 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract; The concrete operations that described solvent percolation extracts are as follows: Radix Vladimiriae is ground into after coarse powder, add concentration to be not less than 75% ethanol, after infiltration, percolation extracts, 60 DEG C of following decompression and solvent recoveries, then extract with water-ethyl acetate system, collect ethyl acetate layer, 60 DEG C of following reclaim under reduced pressure ethyl acetate, 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract; The concrete operations that described solvent refluxing extracts are as follows: Radix Vladimiriae is ground into after coarse powder, add concentration to be not less than 75% ethanol, after infiltration, reflux, extract, 2 ~ 3 times, each 1 ~ 2 hour, merge extractive liquid,, 60 DEG C of following decompression and solvent recoveries, then extract with water-ethyl acetate system, collect ethyl acetate layer, 60 DEG C of following reclaim under reduced pressure ethyl acetate, 60 DEG C of following drying under reduced pressure, obtain Radix Vladimiriae extract;In crude drug, the extracting method of Fructus Hippophae is:Get the mixture of sea buckthorn fruit, seed or fruit and seed and pulverize, extract by solvent method reflux, extract,, supercritical extraction or any method of squeezing centrifuging, collect Oleum Hippophae extract;Wherein, described solvent method reflux, extract, is after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, solvent method reflux, extract,, and by normal heptane, heating and refluxing extraction 2 times, each 4 hours, reclaim solvent, obtain Oleum Hippophae extract; Described supercritical extraction is after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, supercritical CO 2fluid extraction, collects Oleum Hippophae extract through primary separator, and wherein, extracting pressure is 40MPa, and extraction temperature is 65 DEG C, and extraction flow is 18L/h, and flash trapping stage pressure is 6.5MPa, and flash trapping stage temperature is 36 DEG C, obtains Oleum Hippophae extract; Described squeezing centrifuging is that after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, squeezing centrifuging is extracted, and adopts after mechanical expression, obtains slightly oil of Fructus Hippophae, and centrifuging separates, and obtains Oleum Hippophae extract.
- 6. as the purposes of the pharmaceutical composition that is prepared from of the crude drug of following weight proportion in the medicine of preparation treatment chronic atrophic gastritis:18 parts of Radix Vladimiriae extracts, 15 parts of Oleum Hippophae extracts;In described Radix Vladimiriae extract total lactone content in dehydrocostuslactone more than 50%w/w; In described Oleum Hippophae extract containing ester amount in linoleic acid triglyceride more than 50%w/w.
- 7. purposes according to claim 6, is characterized in that: the preparation method of described Oleum Hippophae extract is as follows:Get the mixture of sea buckthorn fruit, seed or fruit and seed and pulverize, extract by solvent method reflux, extract,, supercritical extraction or any method of squeezing centrifuging, collect Oleum Hippophae extract.
- 8. purposes according to claim 7, it is characterized in that: described solvent method reflux, extract, is after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, solvent method reflux, extract,, with normal heptane, heating and refluxing extraction 2 times, each 4 hours, reclaim solvent, obtain Oleum Hippophae extract;Described supercritical extraction is after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, supercritical CO 2fluid extraction, collects Oleum Hippophae extract through primary separator, and wherein, extracting pressure is 40MPa, and extraction temperature is 65 DEG C, and extraction flow is 18L/h, and flash trapping stage pressure is 6.5MPa, and flash trapping stage temperature is 36 DEG C, obtains Oleum Hippophae extract;Described squeezing centrifuging is that after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, squeezing centrifuging is extracted, and adopts after mechanical expression, obtains slightly oil of Fructus Hippophae, and centrifuging separates, and obtains Oleum Hippophae extract.
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CN1730064A (en) * | 2005-06-15 | 2006-02-08 | 肖万郁 | Gastric medicine and its preparation method |
CN101007044A (en) * | 2006-01-23 | 2007-08-01 | 成都中医药大学 | A medicine composition for treating peptic ulcer, preparing method and use thereof |
CN101450092A (en) * | 2007-12-03 | 2009-06-10 | 成都中医药大学 | Vladimiria root extract, composition containing the vladimiria root extract and use thereof |
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CN101007044A (en) * | 2006-01-23 | 2007-08-01 | 成都中医药大学 | A medicine composition for treating peptic ulcer, preparing method and use thereof |
CN101450092A (en) * | 2007-12-03 | 2009-06-10 | 成都中医药大学 | Vladimiria root extract, composition containing the vladimiria root extract and use thereof |
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