CN105616618B - Purposes of the kamuning in terms of preparing Cholagogue drug - Google Patents
Purposes of the kamuning in terms of preparing Cholagogue drug Download PDFInfo
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
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Abstract
The invention discloses a kind of kamuning in the purposes of preparation Cholagogue drug, especially new application of the Folium Et Cacumen Murrayae extract in terms of preparing Cholagogue drug.
Description
Technical field
The present invention relates to the new applications of kamuning, i.e. the purposes in terms of preparing Cholagogue drug.
Background technique
The disease of biliary tract such as cholelithiasis, cholecystitis are global common disease and frequently-occurring disease.By taking cholelithiasis as an example, cholelithiasis hair
It is born in gall-bladder, stones in intrahepatic bile duct and choledochus.Its illness rate is different due to the factors such as race, heredity, geography, diet.20th century 80
In the age, the developed countries such as the U.S., Germany cholelithiasis incidence is about 10%~15%.The total recall rate of China's cholelithiasis is
6.6%, for the recall rate of different regions between 3%~11%, ﹥ 80 years old crowd's disease incidence is up to 23%.Cholelithiasis has gallbladder solid
Point of alcohol calculus, bile pigment calculus and combination calculus, most of is cholesterol stone, accounts for 90% or so.In recent years, due to life
Level is continuously improved, and the intakes such as fat, protein increase in diet, and cholelithiasis disease incidence obviously rises, and patient is more and more.
Meanwhile the disease incidence of cholecystitis also obviously increases, and most of cholecystitis has causality with gall stone.
Often there are the symptoms such as upper abdomen colic pain, shiver with cold fever, jaundice in gall stone, and obstruction of bile duct, canceration, liver can be caused impaired
It is endangered with acute pancreatitis etc., seriously affects patient's physical and mental health.
Cholelithiasis can have an operation treatment, but most people is still based on drug therapy, only under critical condition
Select operative treatment.Therefore, the clinical demand to cholagogic is growing day by day.
Cholagogic, bile secretion can be promoted by referring to, reinforced gallbladder contraction, promoted the drug of gall bladder emptying.Clinical main use
In disease of biliary tract such as cholecystitis, cholelithiasis.According to its effect classification, be divided into promotion bile secretion secretes gallbladder medicine and promotion bile row
The cholekinetic let out.
Western medicine cholagogic market is taken a broad view of, for many years not only Cholagogue drug less varieties, and most of is China in 20th century 70
Start production~the eighties, (such as neocholan, oxaphenamide, Nicotinylmythylamide Hydroxymethylnicotinamide, phenylpropanol, ursodesoxycholic acid, hydroxyl first are fragrant beautiful
The kinds such as element, armillarisin A), few new drugs are released over nearly one, 20 year, and curative effect also complies with one's wishes not to the utmost.Present China market
On, there are some Chinese patent drug cholagogics, such as cholagogic tablet, the easypro glue of relax bladder, XIAOYAN LIDAN PIAN, lidan paishi tablets, compound dantong tablets, gallbladder
Capsule, danshitong capsules etc. can meet patient demand to a certain extent, but curative effect is not still very ideal.To sum up, cholagogic
Status has been unable to meet the demand of current clinic.Therefore it is badly in need of the new cholagogic of research and development good effect, Small side effects.
Kamuning is for the dried leaf of rutaceae murraya paniculataJack Murraya paniculata (L.) Jack and with leaf spray.
Acrid flavour, slight bitter, it is warm-natured, there is the effect of promoting qi circulation and relieving pain, promoting blood circulation to remove blood stasis.Existing literature data shows that kamuning has analgesia, resists
The pharmacological actions such as bacterium, anti-inflammatory, anesthesia, anti-oxidant, inhibition gastrointestinal movement and mitigation diabetic nephropathy renal damage.But it there are no
Close the document report of choleretic effect.
Summary of the invention
The object of the present invention is to provide purposes of the kamuning in terms of preparing Cholagogue drug；
It is a further object of the present invention to provide purposes of the Folium Et Cacumen Murrayae extract in terms of preparing Cholagogue drug；
It is a further object of the present invention to provide purposes of the kamuning ethyl acetate extract in terms of preparing Cholagogue drug；
Kamuning is rutaceae murraya paniculataJackMurraya paniculata(L.) dried leaf of Jack and with leaf spray.
Acrid flavour, slight bitter, it is warm-natured, there is the effect of promoting qi circulation and relieving pain, promoting blood circulation to remove blood stasis, cure mainly stomachache, rheumatic arthralgia, external application smelting is treated toothache, fallen
Flutter swelling and pain, worm snake bite etc..
Inventor observes kamuning alcohol extract, ethyl acetate extract and water using the direct weight method of mouse gall-bladder is won
Influence of the extract to normal mouse and ligation bile duct mouse bile secretion and excretion；Kamuning is observed using rat biliary drainage method
The influence of alcohol extract, ethyl acetate extract to normal rat bile flow and its bile component.It was found that kamuning alcohol extract, second
Acetoacetic ester extract can significantly mitigate the bile coefficient of normal mouse, dramatically increase the bile coefficient of ligation bile duct mouse；Energy
The bile discharge rate of biliary drainage rat is enough dramatically increased, while significantly reducing rat bile total cholesterol level.Show nine li
Alcoholic extract and ethyl acetate extract can promote the secretion and excretion of bile, have choleretic effect.And kamuning water extract
Have the tendency that mitigating the bile coefficient of normal mouse and increase the bile coefficient of ligation bile duct mouse, is i.e. becoming with choleretic effect
Gesture.
Therefore, applicant provides purposes of the kamuning in terms of preparing Cholagogue drug；Especially in Folium Et Cacumen Murrayae extract, nine
The use of fragrant ethanol extract and kamuning ethanol extract through ethyl acetate extract extracted in terms of preparing Cholagogue drug
On the way.
It is a further object of the present invention to provide the preparation methods of kamuning acetic acid ethyl ester extract.
The preparation method of the kamuning acetic acid ethyl ester extract
The following steps are included:
It by kamuning medicinal material drying, crushes, is first extracted with ethyl alcohol, recycle ethyl alcohol and be concentrated, alcohol extract is made；By alcohol extract
It is cleaned with petroleum ether extraction, removes the ingredient for being dissolved in petroleum ether, the alcohol after then being cleaned with ethyl acetate to petroleum ether extraction
Extract is extracted, and carries out recycling ethyl acetate to acetic acid ethyl ester extract, and be concentrated and be prepared.
Specifically, the extracting method of kamuning acetic acid ethyl ester extract of the present invention the following steps are included:
A. kamuning medicinal material drying, the ethyl alcohol heating and refluxing extraction for being 50% or more with concentration expressed in percentage by volume after crushing, filter
It crosses, filtrate recycling ethanol to no alcohol taste is concentrated to give ethanol extract A；
B. add water that suspension is made ethanol extract A, with petroleum ether extraction, discard petroleum ether liquid, remainder is to mention
Take object B；
C. extract B is extracted with ethyl acetate, extract liquor recycling ethyl acetate is simultaneously condensed into cream to get kamuning second
Acetoacetic ester extract.
Preferably,
The extracting method of the kamuning acetic acid ethyl ester extract the following steps are included:
A. kamuning medicinal material drying is taken, after crushing, with the concentration expressed in percentage by volume 50%- for being equivalent to 4-12 times of kamuning weight
After 95% ethyl alcohol impregnates 0.5-2h, filtrate is collected in heating and refluxing extraction 1-3h, filtration；Dregs of a decoction addition is equivalent to kamuning weight
Twice, filtrate is collected in each 1-3h, filtration to the ethyl alcohol heating and refluxing extraction of 4-8 times of concentration expressed in percentage by volume 50%-95%；Merge 3
Secondary filtrate recycles ethyl alcohol to no alcohol taste, is concentrated to give ethanol extract A；
B. by ethanol extract A greenhouse cooling to 0 DEG C hereinafter, then into ethanol extract A be added the ice water with ice cube,
Constantly grinding makes ethanol extract A dissolution that suspension be made during ice melting；Control suspension temperature at 10 DEG C hereinafter,
Then extraction being carried out with petroleum ether to clean, removing the ingredient for being dissolved in petroleum ether, discard petroleum ether extraction liquid, remainder is to mention
Take object B；
C. extract B sufficiently being extracted with ethyl acetate solution, collects extract liquor, recycling ethyl acetate is condensed into medicinal extract,
Up to the kamuning ethyl acetate extract.
The present invention also provides Folium Et Cacumen Murrayae extracts and pharmaceutically acceptable carrier combination to be formed in preparation Cholagogue drug
The new application of aspect.Folium Et Cacumen Murrayae extract cooperates pharmaceutically acceptable carrier, by conventional method in that art be prepared into tablet,
The dosage forms such as granule, capsule, dripping pill, tincture.
Pharmaceutically acceptable carrier of the invention includes but is not limited to following:
Diluent: starch, lactose, dextrin, microcrystalline cellulose, inorganic salts etc..
Wetting agent and adhesive: purified water, ethyl alcohol, gelatin, polyethylene glycol, cellulose derivative etc..
Disintegrating agent: starch, sodium carboxymethyl starch, cellulose derivative, crospovidone etc..
Lubricant: magnesium stearate, superfine silica gel powder, talcum powder, polyethylene glycol etc..
Cosolvent: water, ethyl alcohol, glycerol, propylene glycol, liquid paraffin, vegetable oil etc..
Corrigent: sucrose, monosaccharide, aromatic etc..
Preservative: benzoic acid, sorbic acid, methyl esters, ethyl ester, propyl ester etc..
Existing literature data show kamuning have analgesia, antibacterial, it is anti-inflammatory, anesthesia, it is anti-oxidant, inhibition gastrointestinal movement with
And mitigate the pharmacological actions such as diabetic nephropathy renal damage.But have no the document report in relation to choleretic effect.
New application in terms of kamuning provided by the invention, Folium Et Cacumen Murrayae extract preparation Cholagogue drug has the advantage that
1, Folium Et Cacumen Murrayae extract choleretic effect effect is ideal.To normal mouse and ligation bile duct mouse bile secretion and excretion
The test results such as influence, and influence to normal rat bile flow and its bile component show: kamuning of the present invention mentions
It takes object that can significantly mitigate the bile coefficient of normal mouse, dramatically increases the bile coefficient of ligation bile duct mouse；Can significantly it increase
Add the bile discharge rate of biliary drainage rat, while significantly reducing rat bile total cholesterol level.The prompt present invention can promote
Into the secretion and excretion of bile, there is choleretic effect, provide new material base to be developed into Cholagogue drug, has potential
Huge Social benefit and economic benefit.
2, kamuning herb resource is abundant, and preparation method is simple, raw material sources are conveniently easy to get, can be used for nine li for extraction
A large amount of preparations of fragrant extract.
Specific embodiment
Embodiment 1
A. kamuning medicinal material 1kg is taken, after dry, pulverize, is set in extraction vessel, 95% ethyl alcohol of 4L is added to impregnate 0.5h, heating
Filtrate is collected in refluxing extraction 1.5h, filtration.The dregs of a decoction add 95% ethyl alcohol 5L, extract 1.0h；Filtrate is collected in filtration；The dregs of a decoction add 95% again
Ethyl alcohol 4L extracts 1.0h；Filtrate is collected in filtration.Merge 3 filtrates, recycles ethyl alcohol to no alcohol taste, be concentrated to give ethanol extract A；
B. by ethanol extract A greenhouse cooling to 0 DEG C hereinafter, the ice with ice cube is then added into ethanol extract A
Water, constantly grinding makes ethanol extract A dissolution that suspension be made during ice melting；Control suspension temperature 10 DEG C with
Under, extraction then is carried out with petroleum ether and is cleaned, and is removed the ingredient for being dissolved in petroleum ether, is discarded petroleum ether extraction liquid, remainder
For extract B；
C. extract B sufficiently being extracted with ethyl acetate solution, collects extract liquor, recycling ethyl acetate is condensed into medicinal extract,
Up to the kamuning ethyl acetate extract.
Embodiment 2
A. kamuning medicinal material 1kg is taken, after dry, pulverize, is set in extraction vessel, 75% ethyl alcohol of 8L is added to impregnate 1.0h, heating
Filtrate is collected in refluxing extraction 1h, filtration.The dregs of a decoction add 75% ethyl alcohol 6L, extract 2h；Filtrate is collected in filtration；The dregs of a decoction add 95% ethyl alcohol again
6L extracts 1h；Filtrate is collected in filtration.Merge 3 filtrates, recycling ethyl alcohol is condensed into cream, obtains kamuning ethanol extract A.
B. by ethanol extract A greenhouse cooling to 0 DEG C hereinafter, the ice with ice cube is then added into ethanol extract A
Water, constantly grinding makes ethanol extract A dissolution that suspension be made during ice melting；Control suspension temperature 10 DEG C with
Under, extraction then is carried out with petroleum ether and is cleaned, and is removed the ingredient for being dissolved in petroleum ether, is discarded petroleum ether extraction liquid, remainder
For extract B；
C. extract B sufficiently being extracted with ethyl acetate solution, collects extract liquor, recycling ethyl acetate is condensed into medicinal extract,
Up to the kamuning ethyl acetate extract.
Embodiment 3
A. kamuning medicinal material 1kg is taken, pulverizes and sieves, sets in extraction vessel, adds 60% ethyl alcohol of 10L to impregnate 1.5h, heats back
Stream extracts 2.0h, and filtrate is collected in filtration.The dregs of a decoction add 60% ethyl alcohol 4L, extract 3h；Filtrate is collected in filtration；The dregs of a decoction add 60% ethyl alcohol again
8L refluxing extraction 1h；Filtrate is collected in filtration.Merge 3 filtrates, recycling ethyl alcohol is condensed into cream, obtains kamuning ethanol extract A.
B. by ethanol extract A greenhouse cooling to 0 DEG C hereinafter, the ice with ice cube is then added into ethanol extract A
Water, constantly grinding makes ethanol extract A dissolution that suspension be made during ice melting；Control suspension temperature 10 DEG C with
Under, extraction then is carried out with petroleum ether and is cleaned, and is removed the ingredient for being dissolved in petroleum ether, is discarded petroleum ether extraction liquid, remainder
For extract B；
C. extract B sufficiently being extracted with ethyl acetate solution, collects extract liquor, recycling ethyl acetate is condensed into medicinal extract,
Up to the kamuning ethyl acetate extract.
Embodiment 4
A. kamuning medicinal material 1kg is taken, pulverizes and sieves, sets in extraction vessel, adds 12 L, 50% ethyl alcohol to impregnate 2h, is heated to reflux
3.0h is extracted, filtrate is collected in filtration.The dregs of a decoction add 50% ethyl alcohol 8L, extract 2.0h；Filtrate is collected in filtration；The dregs of a decoction add 50% ethyl alcohol again
8L refluxing extraction 2.0h；Filtrate is collected in filtration.Merge 3 filtrates, recycling ethyl alcohol is condensed into cream, obtains kamuning ethanol extract
A。
B. by ethanol extract A greenhouse cooling to 0 DEG C hereinafter, the ice with ice cube is then added into ethanol extract A
Water, constantly grinding makes ethanol extract A dissolution that suspension be made during ice melting；Control suspension temperature 10 DEG C with
Under, extraction then is carried out with petroleum ether and is cleaned, and is removed the ingredient for being dissolved in petroleum ether, is discarded petroleum ether extraction liquid, remainder
For extract B；
C. extract B sufficiently being extracted with ethyl acetate solution, collects extract liquor, recycling ethyl acetate is condensed into medicinal extract,
Up to the kamuning ethyl acetate extract.
Embodiment 5
Kamuning medicinal material 0.45kg is taken, pulverizes and sieves, sets in extraction vessel, water 10L is added to impregnate 1h, heating is boiled, and is kept
Filtrate is collected in slightly boiled 1h, filtration.The dregs of a decoction add water 10L, extract 2 times, each 1h, and filtrate is collected in filtration.Merge 3 filtrates, it is dense
It is settled to 1000ml with distilled water after contracting, obtains kamuning water extract.4 DEG C of refrigerators save, and face used time mixing.
Embodiment 6
Extract 5ml in Example 5, with distilled water be settled in the volumetric flask of 10ml to get.4 DEG C of refrigerators save,
Face used time mixing.
Embodiment 7
Kamuning medicinal material 0.45kg is taken, pulverizes and sieves, sets in extraction vessel, with the volume for being equivalent to 8 times of kamuning weight
After the ethyl alcohol of percentage concentration 95% impregnates 1h, filtrate is collected in heating and refluxing extraction 2h, filtration；Dregs of a decoction addition is equivalent to kamuning weight
Twice, filtrate is collected in each 1.5h, filtration to the ethyl alcohol heating and refluxing extraction of the concentration expressed in percentage by volume 95% of 6 times of amount；Merge 3 filters
Liquid recycles ethyl alcohol to no alcohol taste, is concentrated to give ointment.Ointment greenhouse cooling is to 0 DEG C hereinafter, being then added into ointment with ice cube
Ice water, constantly grinding makes ointment dissolution that suspension be made during ice melting, is finally settled to 1000ml with distilled water, obtains
Kamuning alcohol extracting thing.4 DEG C of refrigerators save, and face used time mixing.
Embodiment 8
Extract 5ml in Example 7, with distilled water be settled in the volumetric flask of 10ml to get.4 DEG C of refrigerators save,
Face used time mixing.
Embodiment 9
A. kamuning medicinal material 0.45kg is taken, pulverizes and sieves, sets in extraction vessel, with the body for being equivalent to 8 times of kamuning weight
After the ethyl alcohol of product percentage concentration 95% impregnates 1h, filtrate is collected in heating and refluxing extraction 2h, filtration；Dregs of a decoction addition is equivalent to kamuning
Twice, filtrate is collected in each 1.5h, filtration to the ethyl alcohol heating and refluxing extraction for the concentration expressed in percentage by volume 95% that 6 times of weight；Merge 3 times
Filtrate recycles ethyl alcohol to no alcohol taste, obtains kamuning alcohol extracting thing A.
B. by ethanol extract A greenhouse cooling to 0 DEG C hereinafter, the ice with ice cube is then added into ethanol extract A
Water, constantly grinding makes ethanol extract A dissolution that suspension be made during ice melting；Control suspension temperature 10 DEG C with
Under, extraction then is carried out with petroleum ether and is cleaned, and is removed the ingredient for being dissolved in petroleum ether, is discarded petroleum ether extraction liquid, remainder
For extract B；
C. extract B is sufficiently extracted with ethyl acetate solution, collects extract liquor, obtain ointment after recycling ethyl acetate.Medicine
Then cream greenhouse cooling into ointment to 0 DEG C hereinafter, be added the ice water with ice cube, constantly grinding makes medicine during ice melting
Suspension is made in cream dissolution, is finally settled to 1000ml with distilled water, obtains kamuning ethyl acetate extract.4 DEG C of refrigerators save,
Face used time mixing.
Embodiment 10
Extract 5ml in Example 9, with distilled water be settled in the volumetric flask of 10ml to get.4 DEG C of refrigerators are kept,
Face used time mixing.
Embodiment 11
Kamuning medicinal material 1kg is taken, pulverizes and sieves, sets in extraction vessel, water 9L is added to impregnate 1h, heating and refluxing extraction 2h, filter
It crosses, collects filtrate.The dregs of a decoction add water 5L, extract 1h；Filtrate is collected in filtration；The dregs of a decoction add water 5L refluxing extraction 1h；Filtration is collected
Filtrate.Merge 3 filtrates, be condensed into medicinal extract, obtains kamuning water extract.
Embodiment 12
Kamuning medicinal material 1kg is taken, pulverizes and sieves, sets in extraction vessel, water 12L is added to impregnate 2h, heating and refluxing extraction 3h, filter
It crosses, collects filtrate.The dregs of a decoction add water 8L, extract 1h, and filtrate is collected in filtration.Merge 2 filtrates, be condensed into medicinal extract, obtains kamuning water
Extract.
Embodiment 13
Kamuning medicinal material 1kg is taken, pulverizes and sieves, sets in extraction vessel, is impregnated with the ethyl alcohol 10L of concentration expressed in percentage by volume 95%
After 2h, filtrate is collected in heating and refluxing extraction 2h, filtration；The ethyl alcohol 5L heating and refluxing extraction of dregs of a decoction addition concentration expressed in percentage by volume 95%
Filtrate is collected in 1h, filtration；Merge 2 filtrates, recycles ethyl alcohol to no alcohol taste, be condensed into medicinal extract, obtain kamuning alcohol extracting thing.
Embodiment 14
Kamuning medicinal material 1kg is taken, pulverizes and sieves, sets in extraction vessel, is impregnated with the ethyl alcohol 12L of concentration expressed in percentage by volume 95%
After 3h, filtrate is collected in heating and refluxing extraction 3h, filtration, is recycled ethyl alcohol to no alcohol taste, is condensed into medicinal extract, obtains kamuning alcohol extracting
Object.
Experimental example 1: the influence that Folium Et Cacumen Murrayae extract drains normal mouse bile
1 test sample:
1.1 trial drugs: test drug: 5-10 of embodiment of the present invention preparation gained kamuning water extract, alcohol extract and second
Acetoacetic ester extract.
Comparison medicine: bladder of relaxing, lot number 009,503 214, Hanwang Pharmaceutical Industry Co., Ltd., Shanxi.
1.2 animals: Kunming mouse, male, are purchased from Guangxi Medical University's Experimental Animal Center, credit number by SPF grades:
The osmanthus SCXK 2014-0002.
1.3 key instruments: FA1004 type counter scale, upper balance factory, Nereid section；JY1002 electronic balance, Shanghai Pu spring
Metrical instrument Co., Ltd, etc..
2 experimental groups
Blank control group: distilled water
Test 1 group: kamuning water extract high dose group, using the extract of the embodiment of the present invention 5, dosage is
4.50g crude drug/kg；
Test 2 groups: kamuning water extract low dose group, using the extract of the embodiment of the present invention 6, dosage is
2.25g crude drug/kg；
Test 3 groups: kamuning alcohol extract high dose group, using the extract of the embodiment of the present invention 7, dosage is
4.50g crude drug/kg；
Test 4 groups: kamuning alcohol extract low dose group, using the extract of the embodiment of the present invention 8, dosage is
2.25g crude drug/kg；
Test 5 groups: kamuning ethyl acetate extract high dose group gives medicament using the extract of the embodiment of the present invention 9
Amount is 4.50g crude drug/kg；
Test 6 groups: kamuning ethyl acetate extract low dose group is administered using the extract of the embodiment of the present invention 10
Dosage is 2.25g crude drug/kg；
1 group of comparative example: bladder of relaxing, 7.76g crude drug/kg.
3 experimental methods
Take 18~22g of weight mouse 80, be randomly divided into 8 groups, every group 10, respectively blank control group, 1 group of experiment,
Test 2 groups, experiment 3, experiment 4, experiment 5,6 groups and 1 group of comparative example of experiment.Gastric infusion, 1 time/d, continuous 2d, control group is given
Equal volume distilled water.It being administered after 2nd day mouse fasting (can't help water) 16h, 1h after medicine, mouse is put to death in dislocation, gall-bladder weighing is won,
Puncturing gall-bladder flows out bile, is re-weighed after blotting bile with filter paper.Using the difference of front and back weight twice as choleresis, meter
It calculates bile secretion coefficient (mg/10g weight).
Statistical method data withIt indicates；Variance analysis is carried out using 16.0 software of SPSS,P< 0.05 has system
Meter learns meaning.
4 results: as shown in table 1.
1 Folium Et Cacumen Murrayae extract of table to normal mouse bile secretion (excretion) influence (, n=10)
Compared with blank control group: *P< 0.05, * *P <0.01
Table 1 shows compared with blank control group, kamuning alcohol extract 4.50g crude drug/kg dosage, ethyl acetate extract
4.50,2.25g crude drugs/kg dosage can significantly reduce the bile coefficient (promoting bile excretion) of normal mouse, and ethyl acetate mentions
Take object more excellent than the effect of alcohol extract.
Experimental example 2: influence of the murraya paniculataJack extract to ligation bile duct mouse bile secretion
1 test sample:
1.1 trial drugs: test drug: 5-10 of embodiment of the present invention preparation gained kamuning water extract, alcohol extract and second
Acetoacetic ester extract.Comparison medicine: bladder of relaxing, lot number 009,503 214, Hanwang Pharmaceutical Industry Co., Ltd., Shanxi.
1.2 animals: Kunming mouse, male, are purchased from Guangxi Medical University's Experimental Animal Center, credit number by SPF grades:
The osmanthus SCXK 2014-0002.
1.3 key instruments: FA1004 type counter scale, upper balance factory, Nereid section；JY1002 electronic balance, Shanghai Pu spring
Metrical instrument Co., Ltd, etc..
2 experimental groups
Blank control group: distilled water
Model group: distilled water
Test 1 group: kamuning water extract high dose group, using the extract of the embodiment of the present invention 5, dosage is
4.50g crude drug/kg；
Test 2 groups: kamuning water extract low dose group, using the extract of the embodiment of the present invention 6, dosage is
2.25g crude drug/kg；
Test 3 groups: kamuning alcohol extract high dose group, using the extract of the embodiment of the present invention 7, dosage is
4.50g crude drug/kg；
Test 4 groups: kamuning alcohol extract low dose group, using the extract of the embodiment of the present invention 8, dosage is
2.25g crude drug/kg；
Test 5 groups: kamuning ethyl acetate extract high dose group gives medicament using the extract of the embodiment of the present invention 9
Amount is 4.50g crude drug/kg；
Test 6 groups: kamuning ethyl acetate extract low dose group is administered using the extract of the embodiment of the present invention 10
Dosage is 2.25g crude drug/kg；
1 group of comparative example: bladder of relaxing, 7.76g crude drug/kg.
3 experimental methods
22~25g of weight mouse 90 is taken, is randomly divided into 9 groups, every group 10, respectively blank control group, model group, reality
Test 1 group, 2 groups of experiment, 3 groups of experiment, 4 groups of experiment, 5 groups of experiment, 6 groups and 1 group of comparative example of experiment.Gastric infusion, 1 time/d, even
Continuous 5d, Normal group and model group, which are given, waits capacity distilled water.Mouse fasting (can't help water) after 16 hours in 5th day, through ether
Anesthesia, from xiphoid-process under open abdominal cavity, after ligaturing bile duct, suturing them is administered immediately, and mouse is put to death in dislocation after 4h after administration, plucks
It takes gall-bladder and weighs, puncturing gall-bladder flows out bile, is re-weighed after blotting bile with filter paper.Using front and back twice weight difference as
Choleresis calculates bile secretion coefficient (mg/10g weight).
Statistical method data withIt indicates；Variance analysis is carried out using 16.0 software of SPSS,P< 0.05 has system
Meter learns meaning.
4 results: as shown in table 2.
2 murraya paniculataJack extract of table to ligation bile duct mouse bile secretion influence (, n=10)
Compared with model group: *P< 0.05, * *P <0.01
Table 2 the result shows that, kamuning ethyl acetate extract 4.50g crude drug/kg can dramatically increase ligation bile duct mouse
Bile coefficient (promote bile secretion), and water extract, alcohol extract have the tendency that increasing ligation bile duct mouse bile coefficient.
Experimental example 3: influence of the Folium Et Cacumen Murrayae extract to rat bile flow and bile component
1 test sample:
1.1 trial drugs: test drug: 7-10 of embodiment of the present invention preparation gained kamuning alcohol extract, ethyl acetate extract
Object.Comparison medicine: bladder of relaxing, lot number 009,503 214, Hanwang Pharmaceutical Industry Co., Ltd., Shanxi.
1.2 animals: SD rat, male, are provided by Guangxi Medical University's Experimental Animal Center by SPF grades, animal quality certification card
Number: the osmanthus SCXK 2014-0002.
1.3 reagents: total cholesterol assay kit (cholesterol oxidation enzyme process), lot number 20150703, Beijing North inspection are new
Chuan Yuan Bioisystech Co., Ltd；Total bilirubin (T-XZBIL) assay kit (heavy nitrogen), lot number 2015039, Changchun remittance power
Bioisystech Co., Ltd.
1.4 instruments: Thermo Multiskan go all-wave length multi-function microplate reader；Eppendorf Research
Plus single track pipettor；Venous detaining needle, specifications and models: 24G × 19mm/Y-G, Weihai Jierui Medical Products Co., Ltd.；
FA1004 type counter scale, upper balance factory, Nereid section；JY1002 electronic balance, Shanghai Pu Chun metrical instrument Co., Ltd；Deng.
2 experimental groups
Blank control group: distilled water
Test 3 groups: kamuning alcohol extract high dose group, using the extract of the embodiment of the present invention 7, dosage is
4.50g crude drug/kg；
Test 4 groups: kamuning alcohol extract low dose group, using the extract of the embodiment of the present invention 8, dosage is
2.25g crude drug/kg；
Test 5 groups: kamuning ethyl acetate extract high dose group gives medicament using the extract of the embodiment of the present invention 9
Amount is 4.50g crude drug/kg；
Test 6 groups: kamuning ethyl acetate extract low dose group is administered using the extract of the embodiment of the present invention 10
Dosage is 2.25g crude drug/kg；
1 group of comparative example: bladder of relaxing, 7.76g crude drug/kg.
3 experimental methods
300~350 g male rat of weight 60 is taken, is randomly divided into 6 groups, every group 10, respectively blank control group, reality
Test 3 groups, 4 groups of experiment, 5 groups of experiment, 6 groups, 1 group of comparative example of experiment.Gastric infusion, 1 time/d, continuous 3d, blank control group is given
Equal volume distilled water；It is administered after 3rd day Rat Fast (can't help water) 16 h, 30 min anaesthetize (1.25g/ with urethane after medicine
Kg), face upward position to be fixed in fixed plate, open abdominal cavity along abdomen median line, find stomachus pyloricus, overturn duodenum, refer to 12
The bile duct that white flexible is found in intestines drop portion mesenterium wears 2 silk threads under it, ligatures pars papillaris, makees " V " to liver direction
Shape notch makees cystic duct cannula with venous detaining needle, i.e., visible to have the outflow of pistac bile, collects bile with EP pipe.Wait stablize
After 20 min, collect bile 1 time, totally 3 times per hour.Each period bile flow (mL) is recorded, and measures each period bile
Middle total cholesterol and total bilirubin content.
4 results: as shown in table 3, table 4, table 5.
3 Folium Et Cacumen Murrayae extract of table to rat bile flow influence (, n=10)
Compared with blank control group: *P< 0.05, * *P <0.01
4 Folium Et Cacumen Murrayae extract of table to rat bile total cholesterol level influence (, n=10)
Compared with the control group: *P< 0.05, * *P <0.01
5 Folium Et Cacumen Murrayae extract of table to rat bile total bilirubin content influence (, n=10)
Compared with the control group: *P< 0.05, * *P <0.01
Table 3 the result shows that, kamuning alcohol extract 4.50g crude drug/kg dosage and ethyl acetate extract 4.50,2.25g
Crude drug/kg dosage can dramatically increase rat biliary drainage 1h, 2h, 3h；2.25g crude drug/kg dosage dramatically increases bile duct and draws
Flow the bile discharge rate of 2h.
Table 4 the result shows that, kamuning alcohol extract 4.50g crude drug/kg dosage can significantly reduce rat biliary drainage 1h,
2h, 3h；2.25g crude drug/kg dosage significantly reduces total cholesterol level in biliary drainage 2h bile.Kamuning ethyl acetate mentions
Take object 4.50g crude drug/kg dosage that can significantly reduce rat biliary drainage 1h, 2h, 3h；2.25g crude drug/kg dosage significantly drops
Total cholesterol level in low biliary drainage 2h bile.
Table 5 the result shows that, kamuning alcohol extract, ethyl acetate extract 4.50,2.25g crude drug/kg dosage is to each time
The total bilirubin content of section rat bile has no significant effect.
Conclusion Folium Et Cacumen Murrayae extract is to normal mouse with the influence for ligaturing bile duct mouse bile secretion and excretion and to just
The test results such as influence of normal rat bile flow and its bile component are shown: kamuning alcohol extract of the present invention, ethyl acetate mention
It takes object that can significantly mitigate the bile coefficient of normal mouse, dramatically increases the bile coefficient of ligation bile duct mouse；And it can show
The bile discharge rate for increasing rat biliary drainage is write, while significantly reducing rat bile total cholesterol level.And same dose
Kamuning water extract has the tendency that mitigating the bile coefficient of normal mouse and increases the bile coefficient of ligation bile duct mouse.Prompt is originally
Invention Folium Et Cacumen Murrayae extract can remarkably promote the secretion and excretion of bile, have choleretic effect.Folium Et Cacumen Murrayae extract cholagogue is made
With being sequentially ethyl acetate extract > alcohol extract > water extract.
Although above having used general explanation, specific embodiment and test, the present invention is made to retouch in detail
It states, but on the basis of the present invention, it can be made some modifications or improvements, this is apparent to those skilled in the art
's.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, belong to claimed
Range.
Claims (4)
1. purposes of the kamuning acetic acid ethyl ester extract in terms of preparing Cholagogue drug；
The preparation method of the kamuning acetic acid ethyl ester extract the following steps are included:
It by kamuning medicinal material drying, crushes, is first extracted with ethyl alcohol, recycle ethyl alcohol and be concentrated, alcohol extract is made；By alcohol extract stone
Oily ether extraction cleaning, removes the ingredient for being dissolved in petroleum ether, the alcohol extract after then being cleaned with ethyl acetate to petroleum ether extraction
It is extracted, recycling ethyl acetate is carried out to the extract of ethyl acetate, and be concentrated and be prepared.
2. purposes according to claim 1, which is characterized in that the extracting method of the kamuning acetic acid ethyl ester extract
The following steps are included:
A. kamuning medicinal material drying, the ethyl alcohol heating and refluxing extraction for being 50% or more with concentration expressed in percentage by volume after crushing filter, filter
Liquid recycles ethyl alcohol to no alcohol taste, is concentrated to give ethanol extract A；
B. add water that suspension is made ethanol extract A, with petroleum ether extraction, discard petroleum ether liquid, remainder is extract
B；
C. extract B is extracted with ethyl acetate, extract liquor recycling ethyl acetate is simultaneously condensed into cream to get kamuning ethyl acetate
Extract.
3. purposes according to claim 1, which is characterized in that the extracting method of the kamuning acetic acid ethyl ester extract
The following steps are included:
A. kamuning medicinal material drying is taken, after crushing, with the concentration expressed in percentage by volume 50%-95%'s for being equivalent to 4-12 times of kamuning weight
After ethyl alcohol impregnates 0.5-2h, filtrate is collected in heating and refluxing extraction 1-3h, filtration；Dregs of a decoction addition is equivalent to 4-8 times of kamuning weight
Concentration expressed in percentage by volume 50%-95% ethyl alcohol heating and refluxing extraction twice, each 1-3h, filtration, collect filtrate；Merge 3 filters
Liquid recycles ethyl alcohol to no alcohol taste, is concentrated to give ethanol extract A；
B. by ethanol extract A greenhouse cooling to 0 DEG C hereinafter, the ice water with ice cube is then added into ethanol extract A, in ice
Constantly grinding makes ethanol extract A dissolution that suspension be made in block melting process；Suspension temperature is controlled at 10 DEG C hereinafter, then
Extraction is carried out with petroleum ether to clean, and is removed the ingredient for being dissolved in petroleum ether, is discarded petroleum ether extraction liquid, remainder is extract
B；
C. extract B is sufficiently extracted with ethyl acetate solution, collect extract liquor, recycling ethyl acetate be condensed into medicinal extract to get
The kamuning acetic acid ethyl ester extract.
4. the kamuning acetic acid ethyl ester extract as described in claim 1-3 any one is matched with pharmaceutically acceptable carrier
Close the purposes in terms of Cholagogue drug is made.
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Application publication date: 20160601 Assignee: GUANGXI WUZHOU SANHE PHARMACEUTICAL CO.,LTD. Assignor: GUANGXI INSTITUTE OF CHINESE MEDICINE & PHARMACEUTICAL SCIENCE Contract record no.: X2022450000393 Denomination of invention: Application of Jiuli Xiang in the preparation of cholagogic drugs Granted publication date: 20191126 License type: Common License Record date: 20221226 |