CN102716169A - 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 preceding disease of gastric cancer (annual canceration rate is 0.5%～1%); Pathologic finding gastric mucosa atrophy attenuation, body of gland composition reduce or disappear, and clinical manifestation is gastral cavilty distension or distending pain, heating installation, noisy, inappetence, become thin etc., belong to disease categories such as Chinese medicine feeling of fullness, noisy, stomachache.What all think chronic atrophic gastritis for a long time is result of various factor comprehensive action; Like helicobacter pylori infections, peptic ulcer; And it also changes with its activeness and difficulty is more relevant repeatedly, and is relevant to infecting 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 clinical research guideline: 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 common recognition suggestion (2009, Shenzhen). 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 treatment processing such as gastric motility, yet doctor trained in Western medicine is unsatisfactory to the curative effect of chronic atrophic gastritis, also finds the specific drug to this disease; And Chinese medicine, Tibetan medicine and pharmacology can improve clinical symptoms, alleviate mucosa infection; Play a role through strengthening the gastric mucosal protection function; Even can stop the generation of CAG canceration, untoward reaction relatively seldom has the curative effect of consolidation, prevents comprehensive functions such as recurrence and whole body adjustment; In the treatment of chronic atrophic gastritis, have remarkable advantages [Yang Liqiong. the progress of therapy of combining Chinese and Western medicine chronic atrophic gastritis. medical information .2010,23 (8): 2689; More the Tibetan adds, and Ga Zang arranges, Wei Gang. and the Tibetan medicine treats chronic atrophic gastritis 76 examples. 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 Radix Vladimiriae platymiscium Radix Vladimiriae Vladimiria souliei (Franch.) Ling. and gray wool Radix Vladimiriae Vladimiria souliei (Franch.) Ling var.cinerea Ling.; Nature and flavor are hot, bitter, warm; The function promoting the circulation of QI to relieve pain; Be used to treat diseases such as abdominal distention, liver and gall pain [Chinese Pharmacopoeia Commission. one one of Pharmacopoeia of People's Republic of China version in 2005. Beijing: the .2005:41 of Chemical Industry Press], be one of medicine commonly used of treatment digestive tract disease.Radix Vladimiriae be in, hide to intersect medicine variety; All on the books in the classical masterpiece Four-Volume Medical Code of Tibetan medicine, " brilliant pearl book on Chinese herbal medicine "; Clear " Baconic " heat of function, blood-activating analgetic, spleen invigorating removing food stagnancy; Control diseases such as stomach abdominal distention and pain due to " Baconic " heat symptom-complex, the QI and blood amount discord, hypochondriac pain [the Luo Dashang chief editor. book on Chinese herbal medicine is hidden by China. Beijing: Nationalities Press, 1997.265; The institute for drug control, Qinghai Province, the chief editor of Qinghai Tibet Medical Institute. Shanghai: Shanghai science tech publishing house, 1996, the second volume .120].Number of patent application: disclose Radix Vladimiriae in 200710202833.6 and be used for the purposes that peptic ulcer is prevented and treated.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 is as one of numerous predisposing factorss of chronic atrophic gastritis, under the situation of its long-term pessimal stimulation or faulty union; Possibly increase the incidence probability of chronic atrophic gastritis; But do not have necessary connection between the two, and peptic ulcer mainly is non-atrophic acute stage disease (with ulcer is main, and body of gland is complete); There were significant differences (with cellular infiltration is main, and body of gland is impaired) with chronic atrophic gastritis.
At present, also do not see with the single usefulness of Radix Vladimiriae or with the relevant report of treating chronic atrophic gastritis behind Radix Vladimiriae extract and the Oleum Hippophae extract compatibility.
Summary of the invention
Technical scheme of the present invention has provided the new purposes of Radix Vladimiriae or its extract.Another technical scheme of the present invention has provided the new purposes of the pharmaceutical composition behind Radix Vladimiriae or its extract and Fructus Hippophae or the Oleum Hippophae extract compatibility.
The invention provides Radix Vladimiriae or its extract purposes in the medicine of preparation treatment chronic atrophic gastritis.
Further, said medicine is the promotion enterokinesia, improves duodenum smooth muscle contraction ability, treatment autoimmune or/and the medicine of the chronic atrophic gastritis due to the bile reflux.
Further, in the described Radix Vladimiriae extract total lactone content in dehydrocostuslactone more than 50%w/w.
Wherein, described Radix Vladimiriae preparation method of extract is:
Get Radix Vladimiriae and be ground into coarse powder, adopt supercritical extraction or solvent supersonic to extract or the extraction of solvent percolation or any method for distilling of solvent refluxing extraction, collect the Radix Vladimiriae extract.
Further, the concrete operations of said supercritical extraction are following: after Radix Vladimiriae is ground into coarse powder, adopt supercritical fluid carbon dioxide to extract, separate, behind the drying under reduced pressure, promptly get the Radix Vladimiriae extract below 60 ℃;
The concrete operations that said solvent supersonic extracts are following: after Radix Vladimiriae was ground into coarse powder, adding concentration was not less than 75% ethanol, after the infiltration; Supersound extract, decompression and solvent recovery below 60 ℃ is again with water-ethyl acetate system extraction; Collect ethyl acetate layer; 60 ℃ of following reclaim under reduced pressure ethyl acetate, drying under reduced pressure below 60 ℃ promptly gets the Radix Vladimiriae extract;
The concrete operations that said solvent percolation extracts are following: after Radix Vladimiriae was ground into coarse powder, adding concentration was not less than 75% ethanol, after the infiltration; Percolation extracts, and decompression and solvent recovery below 60 ℃ is again with water-ethyl acetate system extraction; Collect ethyl acetate layer; 60 ℃ of following reclaim under reduced pressure ethyl acetate, drying under reduced pressure below 60 ℃ promptly gets the Radix Vladimiriae extract;
The concrete operations that said solvent refluxing extracts are following: after Radix Vladimiriae was ground into coarse powder, adding concentration was not less than 75% ethanol, after the infiltration; Reflux, extract, 2 ~ 3 times, each 1 ~ 2 hour, merge extractive liquid; Decompression and solvent recovery below 60 ℃ with water-ethyl acetate system extraction, is collected ethyl acetate layer again; 60 ℃ of following reclaim under reduced pressure ethyl acetate, drying under reduced pressure below 60 ℃ promptly gets the Radix Vladimiriae extract.
The present invention also provides the purposes of the pharmaceutical composition that is prepared from like following raw materials by weight proportions 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 that is prepared from the following weight proportion raw material:
3 parts of Radix Vladimiriaes, 1.5 parts of Fructus Hippophaes.
The present invention also provides the purposes of the pharmaceutical composition that is prepared from like following raw materials by weight proportions 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 that is prepared from the following weight proportion raw material:
18 parts of Radix Vladimiriae extracts, 15 parts of Oleum Hippophae extracts.
Wherein, in the described Radix Vladimiriae extract total lactone content in dehydrocostuslactone more than 50%w/w; Contain in the described Oleum Hippophae extract ester amount in linoleic acid triglyceride more than 50%w/w.
Further, described Oleum Hippophae preparation method of extract is following:
Get the mixture of sea buckthorn fruit, seed or fruit and seed and pulverize, extract, collect the Oleum Hippophae extract with solvent method reflux, extract,, supercritical extraction or any method of squeezing centrifuging.
Further, described solvent method reflux, extract, is that the solvent method reflux, extract, was used normal heptane after the mixture of sea buckthorn fruit, seed or fruit and seed was pulverized, heating and refluxing extraction 2 times, and each 4 hours, reclaim solvent, promptly get the Oleum Hippophae extract;
Said supercritical extraction is after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, supercritical CO
2Fluid extraction is collected the Oleum Hippophae extract through primary separator, and wherein, extracting pressure is 40MPa, and extraction temperature is 65 ℃, and the extraction flow is 18L/h, and flash trapping stage pressure is 6.5MPa, and the flash trapping stage temperature is 36 ℃, promptly gets the Oleum Hippophae extract;
Described squeezing centrifuging is that the squeezing centrifuging was extracted after the mixture of sea buckthorn fruit, seed or fruit and seed was pulverized, and behind the employing mechanical expression, gets slightly oil of Fructus Hippophae, and centrifuging is separated, and promptly gets the 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 the gastrointestinal motility and the pathological symptom of chronic atrophic gastritis; Especially be directed against autoimmune or/and the chronic atrophic gastritis due to the bile reflux has the good curing effect; Simultaneously, the present invention has brought into play synergistic function after Radix Vladimiriae and Fructus Hippophae compatibility are used, and treatment chronic atrophic gastritis effect is more obvious, for clinical application provides new selection.
The specific embodiment
Embodiment 1 Radix Vladimiriae preparation method of extract
Get Radix Vladimiriae and be ground into coarse powder, adopt supercritical extraction or solvent supersonic to extract or the extraction of solvent percolation or any method for distilling of solvent refluxing extraction, collect the Radix Vladimiriae extract.
A, Radix Vladimiriae is ground into coarse powder after, adopt supercritical fluid carbon dioxide to extract, separate, behind the drying under reduced pressure, promptly get the Radix Vladimiriae extract below 60 ℃;
The concrete operations that b, said solvent supersonic extract are following: after Radix Vladimiriae was ground into coarse powder, adding concentration was not less than 85% ethanol, after the infiltration; Supersound extract, decompression and solvent recovery below 60 ℃ is again with water-ethyl acetate system extraction; Collect ethyl acetate layer; 60 ℃ of following reclaim under reduced pressure ethyl acetate, drying under reduced pressure below 60 ℃ promptly gets the Radix Vladimiriae extract;
The concrete operations that c, said solvent percolation extract are following: after Radix Vladimiriae was ground into coarse powder, adding concentration was not less than 85% ethanol, after the infiltration; Percolation extracts, and decompression and solvent recovery below 60 ℃ is again with water-ethyl acetate system extraction; Collect ethyl acetate layer; 60 ℃ of following reclaim under reduced pressure ethyl acetate, drying under reduced pressure below 60 ℃ promptly gets the Radix Vladimiriae extract;
The concrete operations that d, said solvent refluxing extract are following: after Radix Vladimiriae was ground into coarse powder, adding concentration was not less than 85% ethanol, after the infiltration; Reflux, extract, 2 ~ 3 times, each 1 ~ 2 hour, merge extractive liquid; Decompression and solvent recovery below 60 ℃ with water-ethyl acetate system extraction, is collected ethyl acetate layer again; 60 ℃ of following reclaim under reduced pressure ethyl acetate, drying under reduced pressure below 60 ℃ promptly gets the Radix Vladimiriae extract.
According to Chinese patent: the method for quality control of embodiment 8 carries out assay to the Oleum Hippophae extract in 200610020203.2, and its result sees the following form:
Table 1
Above result shows that the extraction efficiency of above-mentioned 4 kinds of methods is close.The said extracted method can be referring to Chinese patent: embodiment 1 in 200610020203.2.
Embodiment 2 Oleum Hippophae preparation method of extract
Get the mixture of sea buckthorn fruit, seed or fruit and seed and pulverize, extract, collect the Oleum Hippophae extract with solvent method reflux, extract,, supercritical extraction or any method of squeezing centrifuging.
Method one: described solvent method reflux, extract, is that the solvent method reflux, extract, was used normal heptane after the mixture of sea buckthorn fruit, seed or fruit and seed was pulverized, heating and refluxing extraction 2 times, and each 4 hours, reclaim solvent, promptly get the Oleum Hippophae extract;
Method two: said supercritical extraction is after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, supercritical CO
2Fluid extraction is collected the Oleum Hippophae extract through primary separator, and wherein, extracting pressure is 40MPa, and extraction temperature is 65 ℃, and the extraction flow is 18L/h, and flash trapping stage pressure is 6.5MPa, and the flash trapping stage temperature is 36 ℃, promptly gets the Oleum Hippophae extract;
Method three: described squeezing centrifuging is that the squeezing centrifuging was extracted after the mixture of sea buckthorn fruit, seed or fruit and seed was pulverized, and behind the employing mechanical expression, gets slightly oil of Fructus Hippophae, and centrifuging is separated, and promptly gets the Oleum Hippophae extract.
According to Chinese patent: the method for quality control of embodiment 9 carries out assay to the Oleum Hippophae extract in 200610020203.2, and its result sees the following form:
Table 2
The said extracted method can be referring to Chinese patent: embodiment 2 in 200610020203.2.Below through Test Example beneficial effect of the present invention is described.
Each medicine of Test Example 1 the present invention is to the pharmacodynamics screening test of chronic atrophic gastritis
One, receives the preparation of reagent thing
The Radix Vladimiriae extract: the method for distilling d preparation according to embodiment 1, add Polyethylene Glycol-400 again and process the solution that every 1ml contains the 0.5g primary crude drug, subsequent use.By middle regulation Radix Vladimiriae primary crude drug Coming-of-Age Day consumption of Chinese Pharmacopoeia version in 2010 is 3～9g/60kg, and mice consumption proportionately 60 times of people's consumption is converted, i.e. 3～9g/kg; The content of Radix Vladimiriae extract is about 6% in the Radix Vladimiriae, and promptly Radix Vladimiriae extract mice consumption is 0.18～0.54g/kg.
Oleum Hippophae extract: according to method for distilling three preparations of embodiment 2.By middle regulation Fructus Hippophae primary crude drug Coming-of-Age Day consumption of Chinese Pharmacopoeia version in 2010 is 3～9g/60kg, and mice consumption proportionately 60 times of people's consumption is converted, i.e. 3～9g/kg; The content of Oleum Hippophae extract is about 10% in the Fructus Hippophae, and promptly 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 and carry out the integrated approach that active immunity and bile and hot water are irritated stomach simultaneously, make rat atrophic property 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 the Freuud adjuvant is made into 1:1) 0.3ml, duplicate injection is 1 time after 1 month.(2) bile is irritated stomach: when doing initiatively immunity, adopt the bile of no suppurative inflammation patient's drain, give rat oral gavage (irritate stomach and stopped eating in preceding 4 hours, freely drink water), every day 1 time, continuous 70 days by 12.5ml/kg.(3) hot water is irritated stomach: (irritated stomach 5 hours at interval with bile) on the same day what irritate stomach with bile, irritate stomaches with 50 ℃ of hot water 12.5ml/kg, every day 1 time, continuous 7O days.
2.2 normal group
Normal saline 12.5ml/kg irritates stomach, every day 2 times (irritating the stomach time synchronized with model group), continuous 70 days.
2.3 administration group and positive drug administration group
Get the model group rat, random packet is irritated stomach 1 time by uniform Design dosage, continuous 60 days every day.
Each treated animal is conventional raises, and administration is carried out histopathologic examination after finishing, and observes therapeutic outcome.
Table 3 factor level table
Table 4 screening test table and table as a result
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 each symptom of organizing chronic atrophic gastritis of pathologic finding data declaration and have significant improvement effect.
Adopt DAS that data are carried out the quadratic polynomial stepwise regression analysis:
Y=197.5-773.6*X1-13.3*X2+1118.8*X1*X1
Regression equation meaningful (P=0.0558), wherein X1 is a utmost point appreciable impact factor (P=0.0073), and X1*X1 is a utmost point appreciable impact factor (P=0.0063), and X2 is a non-appreciable impact factor (P=0.2753).
Optimization analysis result to the influence factor shows: when the X1 value be 0.18, when the X2 value is 0.15, regression equation is obtained maximum, when promptly conversion is Radix Vladimiriae 3g/kg, Fructus Hippophae 1.5g/kg for the medical material consumption, to improvement effect the best of chronic atrophic gastritis.
The pathological observation conclusion:
The 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 the mucosa pinkiness is glossy, no petechia, and blood vessel is not obvious under the mucosa.Mirror observation gastric mucosa thickness down is big, and epithelium is complete, the epithelial cell marshalling, and nothing comes off or is damaged, and cell is the monolayer column, and glandular epithelium and glandular tube boundary are clear, lamina propria body of gland regular shape.
The attenuation of model group rat coat of the stomach, poor flexibility, gastric content increases, and pleat is low flat, moves towards disorderly, disappears than multizone especially gastric antrum portion pleat, and mucus is few, and the mucosa color and luster is greyish white, it is thus clear that be dispersed in the petechia, blood vessel is high-visible under the mucosa.Mirror is observed the gastric mucosa layer attenuation down, and is imperfect, visible degeneration in various degree or downright bad exfoliative cyte, and body of gland atrophy or disappearance in various degree, a matter has multiple inflammatory cell (being mainly lymphocyte and plasma cell) to soak into.
Administration group epithelial cell is complete relatively, and cellular morphology is normal, and body of gland is arranged and owed regular slightly.Flesh layer progressive additive, thickness is more even.The top layer mucosa does not have and comes off, and body of gland does not have obvious atrophy; Cell infiltration significantly reduces in gastric antrum portion, glandular stomach and the stomach intersection lamina propria.Lamina propria edema, vasodilation improve than model group.
From above-mentioned experiment, find out; Radix Vladimiriae extract, Oleum Hippophae extract use all the relevant symptoms to chronic atrophic gastritis due to the bile reflux that certain improvement effect is arranged separately; Most experiments has all embodied the effect that is superior to single medicine behind the two compatibility, and explaining behind both compatibilities has certain synergistic function; And two medicines are introduced as the influence factor in the regression equation, and certain synergistic function is described.
Test Example 2 Radix Vladimiriae extracts are to the influence of enterokinesia and duodenum smooth muscle
Chronic atrophic gastritis patient; Certain stomach-pylorus-duodenum dyskinesia is arranged, and this also is one of reveal any symptoms after the body of gland atrophy, therefore; Medicine can play certain improvement effect to the symptom of chronic atrophic gastritis to the adjusting of enterokinesia, duodenum smooth muscle movement ability.Below through of the influence of effect experiment explanation Radix Vladimiriae extract to enterokinesia, duodenum smooth muscle.
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 big ear of Japan is white, the laboratory animal quality certification number is provided: 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, process extractum, extract, obtain the ethyl acetate position with ethyl acetate with 75% ethanol percolation.Can know through extractant method optimization experiment, ethanol extract behind ethyl acetate extraction, the effective 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 (chemical chemical reagent work of burnt alkali group, 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 (goes up marine rainbow photoinitiator chemical factory, lot number: 010421) Long Huagongshijichang of Chengdu section, lot number:; Calcium chloride (chemical plant among Deng of 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 letter He Huagongshijichang, lot number: 030405).
1.4 experimental apparatus
Magnus' bath (50ml type); BL-410 microcomputer type bio signal is gathered 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 equipment station).
2. experimental technique and result
2.1 each extract of Radix Vladimiriae is to the influence of mice enterokinesia
Get 120 of white mice, male and female half and half, laboratory rearing 3 days is divided into 13 groups at random; Every group 10, water 24h is can't help in fasting, and the continuous irrigation stomach gave the respective concentration drug group 3 days, behind the last administration 30min; Only irritate clothes carbon powder suspension (10% active carbon, 10% arabic gum) 0.2mL/, put to death behind the 20min; Open the abdominal cavity, separate mesentery, the clip upper end is to pylorus; The lower end places on glass, gently that small intestinal is stretching to the intestinal tube of ileocecum portion; Measuring intestinal tube length with ruler is " small intestinal total length ", and the distance from pylorus to the carbon powder forward position is " carbon powder is at the advance distance of enteral ", calculates carbon powder and advances percentage rate (carbon powder propelling percentage rate (%)=carbon powder advance distance (cm)/small intestinal total length (cm) * 100%.The result sees the following form.
Table 5 Radix Vladimiriae extract is to the influence
of mice enterokinesia
Annotate: * and blank group compare, and P < 0.05; * and blank group compare, and P < 0.01
The result shows: the motilium group can promote enterokinesia (P＜0.01) fairly obviously, and the ethyl acetate high dose group can obviously promote enterokinesia (P＜0.05).
2.2 each extract of Radix Vladimiriae is to the enhanced influence of rabbit duodenum smooth muscle contraction ability due to the acetylcholine
Adjustment Magnus' bath, oxygen generator, pressure transducer and BL-410 microcomputer type bio signal are gathered and processing system, make operate as normal, zeroing and calibration.Get rabbit (fasting 12h before the experiment), hit occipital bone with wooden mallet and put to death, cut the abdominal cavity immediately open; Take out one section of duodenum; Place the beaker that fills tyrode's solution, fall mesentery along the 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, observes the motion of normal myenteron earlier; Myenteron tension force in the adjustment Magnus' bath; Making relaxes contract stablize 10-30min after; The curve of tracing one section myenteron proper motion drips various medicinal liquids (seeing after) then again in Magnus' bath, the relax curve that contracts of immediate record (is all used tyrode's solution flushing myenteron 2-3 time before dripping medicinal liquid at every turn; Fresh body lotion can stop 1～2min and bleed off then, waits to relax to contract to return to before the medication to add group medicinal liquid down again after the level).
The order of administration of acetylcholine modeling: can on a myenteron, accomplish following experiment.Observe the effect of Radix Vladimiriae extract solution: 1. write down normal value; 2. add acetylcholine solution 25 μ l behind the 60s; 3. add Radix Vladimiriae behind the 30s and extract solution 100 μ l; 4. add Radix Vladimiriae behind the 30s again and extract solution 100 μ l; 5. add Radix Vladimiriae behind the 30s again and extract solution 100 μ l; With tyrode's solution flushing myenteron 2～3 times, fresh body lotion can stop 1～2min and bleed off then, waits that relaxing contracts and return to add group medicinal liquid down again after the level before the medication.Observe atropinic effect (because atropinic inhibitory action is too strong, so the experiment of putting behind): 9. write down normal value; 10. add acetylcholine solution 25 μ l behind the 60s; (11) add atropine 25 μ l behind the 30s; With tyrode's solution flushing myenteron 2～3 times, fresh body lotion can stop 1～2min and bleed off then, waits that relaxing contracts and return to add group medicinal liquid down again after the level before the medication.Experimental result sees the following form.
Table 6 Radix Vladimiriae extract is to the enhanced influence of rabbit duodenum smooth muscle contraction ability
due to the 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 |
Annotate: * and blank group compare, and P < 0.05; * and blank group compare, and P < 0.01.
The result shows, the atropine group can obviously suppress acetylcholine to the contraction of smooth muscle (P < 0.01), and the 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 the gastrointestinal motility and the pathological symptom of chronic atrophic gastritis, especially be directed against autoimmune or/and the chronic atrophic gastritis due to the bile reflux has the good curing effect; Simultaneously, the present invention has brought into play synergistic function after Radix Vladimiriae and Fructus Hippophae compatibility are used, and treatment chronic atrophic gastritis effect is more obvious, for clinical application provides new selection.
Claims (12)
1. Radix Vladimiriae or its extract purposes in the medicine of preparation treatment chronic atrophic gastritis.
2. purposes according to claim 1 is characterized in that: said 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 the bile reflux.
3. purposes according to claim 1 is characterized in that: in the described Radix Vladimiriae extract total lactone content in dehydrocostuslactone more than 50%w/w.
4. according to any described purposes of claim 1-3, it is characterized in that: described Radix Vladimiriae preparation method of extract is:
Get Radix Vladimiriae and be ground into coarse powder, adopt supercritical extraction or solvent supersonic to extract or the extraction of solvent percolation or any method for distilling of solvent refluxing extraction, collect the Radix Vladimiriae extract.
5. purposes according to claim 4; It is characterized in that: the concrete operations of said supercritical extraction are following: after Radix Vladimiriae is ground into coarse powder; Adopt supercritical fluid carbon dioxide to extract, separate, behind the drying under reduced pressure, promptly get the Radix Vladimiriae extract below 60 ℃;
The concrete operations that said solvent supersonic extracts are following: after Radix Vladimiriae was ground into coarse powder, adding concentration was not less than 75% ethanol, after the infiltration; Supersound extract, decompression and solvent recovery below 60 ℃ is again with water-ethyl acetate system extraction; Collect ethyl acetate layer; 60 ℃ of following reclaim under reduced pressure ethyl acetate, drying under reduced pressure below 60 ℃ promptly gets the Radix Vladimiriae extract;
The concrete operations that said solvent percolation extracts are following: after Radix Vladimiriae was ground into coarse powder, adding concentration was not less than 75% ethanol, after the infiltration; Percolation extracts, and decompression and solvent recovery below 60 ℃ is again with water-ethyl acetate system extraction; Collect ethyl acetate layer; 60 ℃ of following reclaim under reduced pressure ethyl acetate, drying under reduced pressure below 60 ℃ promptly gets the Radix Vladimiriae extract;
The concrete operations that said solvent refluxing extracts are following: after Radix Vladimiriae was ground into coarse powder, adding concentration was not less than 75% ethanol, after the infiltration; Reflux, extract, 2 ~ 3 times, each 1 ~ 2 hour, merge extractive liquid; Decompression and solvent recovery below 60 ℃ with water-ethyl acetate system extraction, is collected ethyl acetate layer again; 60 ℃ of following reclaim under reduced pressure ethyl acetate, drying under reduced pressure below 60 ℃ promptly gets the Radix Vladimiriae extract.
6. the purposes of pharmaceutical composition in the medicine of preparation treatment chronic atrophic gastritis that is prepared from like following raw materials by weight proportions:
1～9 part of Radix Vladimiriae, 1～9 part of Fructus Hippophae.
7. purposes according to claim 6 is characterized in that: described medicine is the preparation that is prepared from the following weight proportion raw material:
3 parts of Radix Vladimiriaes, 1.5 parts of Fructus Hippophaes.
8. the purposes of pharmaceutical composition in the medicine of preparation treatment chronic atrophic gastritis that is prepared from like following raw materials by weight proportions:
18～54 parts of Radix Vladimiriae extracts, 15～90 parts of Oleum Hippophae extracts.
9. purposes according to claim 8 is characterized in that: described medicine is the preparation that is prepared from the following weight proportion raw material:
18 parts of Radix Vladimiriae extracts, 15 parts of Oleum Hippophae extracts.
10. it is characterized in that according to Claim 8 or 9 described purposes: in the described Radix Vladimiriae extract total lactone content in dehydrocostuslactone more than 50%w/w; Contain in the described Oleum Hippophae extract ester amount in linoleic acid triglyceride more than 50%w/w.
11. purposes according to claim 10 is characterized in that: described Oleum Hippophae preparation method of extract is following:
Get the mixture of sea buckthorn fruit, seed or fruit and seed and pulverize, extract, collect the Oleum Hippophae extract with solvent method reflux, extract,, supercritical extraction or any method of squeezing centrifuging.
12. purposes according to claim 11; It is characterized in that: described solvent method reflux, extract, is for after pulverizing the mixture of sea buckthorn fruit, seed or fruit and seed, and the solvent method reflux, extract, is used normal heptane; Heating and refluxing extraction 2 times; Each 4 hours, reclaim solvent, promptly get the Oleum Hippophae extract;
Said supercritical extraction is after the mixture of sea buckthorn fruit, seed or fruit and seed is pulverized, supercritical CO
2Fluid extraction is collected the Oleum Hippophae extract through primary separator, and wherein, extracting pressure is 40MPa, and extraction temperature is 65 ℃, and the extraction flow is 18L/h, and flash trapping stage pressure is 6.5MPa, and the flash trapping stage temperature is 36 ℃, promptly gets the Oleum Hippophae extract;
Described squeezing centrifuging is that the squeezing centrifuging was extracted after the mixture of sea buckthorn fruit, seed or fruit and seed was pulverized, and behind the employing mechanical expression, gets slightly oil of Fructus Hippophae, and centrifuging is separated, and promptly gets the Oleum Hippophae extract.
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