CN107648294A - The purposes in treating vascular dementia medicine is being prepared containing the double-colored golden wave active component of marein - Google Patents
The purposes in treating vascular dementia medicine is being prepared containing the double-colored golden wave active component of marein Download PDFInfo
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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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
- A61K2236/30—Extraction of the material
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- A—HUMAN NECESSITIES
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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
- A61K2236/50—Methods involving additional extraction steps
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Abstract
The present invention relates to a kind of the purposes in treating vascular dementia medicine is being prepared containing the double-colored golden wave active component of marein, it is the total flavone valid target extracted from the capitulum of the double-colored golden wave of the peculiar medical and edible dual purpose plant in Xinjiang, shown by experimental study, the double-colored golden wave active component containing marein can substantially shorten the escape latency of vascular dementia rats;Improve vascular dementia rats 120s spanning platform numbers;Raise the superoxide dismutase in cortex, hippocampus, choline acetyl transferase, acetylcholine activity;Mda content is reduced, significantly improves human neuroblastoma cells' strain of Hydroperoxide injury(SH‑SY5Y)Cell survival rate, have and protect neural cytosis;And the hypertension to inducing vascular dementia has good therapeutic action, while there is protective effect to oxidativestress damage caused by hypertension.The medicine for preparing treatment vascular dementia for raw material for double-colored golden wave provides new approach.
Description
Technical field
The present invention relates to pharmaceutical technology field, relates generally to the medicine that vascular dementia is treated in the extraction from double-colored golden wave
Purposes.
Background technology
Vascular dementia (vascular dementia, VD), refers to cause brain tissue damage by a series of cerebrovascular factors
Caused one group of clinical syndrome characterized by cognitive decrease, it is to be only second to Alzheimer disease (Alzheimer ' s
Disease, AD) second largest common dementia type.In the Asian countries such as China and Japan, vascular dementia accounts for all kinds of dementias
The 1st of morbidity, it has also become seriously endanger the clinical common disease of human life and health and quality of life.Therefore, to this disease
Prevent and treat significant.
Vascular dementia (VD) has potentially preventing and treating property, is referred to as " cataphrenia ".Research finds that hypertension is
The important risk factor for causing vascular dementia (VD) to occur.Cerebral white matter damage caused by long-term hypertension can cause to recognize work(
It can decline, hypertension increases antihypertensive drugs that is significantly correlated, and implying good with Onset of Vascular Dementia danger, is to prevent blood
The key measure of pipe dementia development.
Double-colored golden wave is originated in the Karakorum mountain of more than 3000 meters of Xinjiang height above sea level, also known as snow chrysanthemum, and it ties up language title
It is the dry capitulum of composite family (Compositae) golden pheasant Chrysanthemum (Coreopsis) for " ancient just beautiful you " (Gulqai), it is single
Valve, polyphyll or half polyphyll, ligulate flower, yellow or golden yellow.Local resident selects " snow chrysanthemum " to be quoted when tea more, because of its good drop
Blood pressure, antilipemic healthy effect, among the people extensive favorable comment is obtained local.And, it has been found that often drink " snow chrysanthemum " dimension I
Your race old man not only has preferable blood pressure, blood fat, and also clear-headed and clear-sighted, thinking is clear, very occurs senile dementia less.
The double-colored golden wave active component containing marein can substantially shorten the escape latency of vascular dementia rats;Improve
Vascular dementia rats 120s spanning platform numbers;Raise the superoxide dismutase (SOD) in cortex, hippocampus, choline acetyl
Change transferase (ChAT), acetylcholine (AChE) activity;MDA (MDA) content is reduced, significantly improves Hydroperoxide injury
Human neuroblastoma cells' strain (SH-SY5Y) cell survival rate, have and protect neural cytosis;And it is crazy about to inducing vascular
Slow-witted hypertension etc. has good therapeutic action, while has protective effect to oxidativestress damage caused by hypertension, tool
There is treatment of vascular dementia.
The content of the invention
It is crazy about it is an object of the present invention to provide one kind containing the double-colored golden wave active component of marein in preparation treatment vascular
Purposes in slow-witted medicine, is that the general flavone extracted from the capitulum of the double-colored golden wave of the peculiar medical and edible dual purpose plant in Xinjiang has
Position is imitated, capsule, granule, tablet then is made according to traditional drug formulations method in the total flavone valid target of extraction
Or pill uses.Shown by experimental study, the double-colored golden wave active component containing marein can substantially shorten blood vessel
The escape latency of dementia rats;Improve vascular dementia rats 120s spanning platform numbers;Raise super in cortex, hippocampus
Superoxide dismutase (SOD), choline acetyl transferase (ChAT), acetylcholine (AChE) activity;MDA (MDA) is reduced to contain
Amount, human neuroblastoma cells' strain (SH-SY5Y) cell survival rate of Hydroperoxide injury is significantly improved, there is protection nerve
Cytosis;And the hypertension to inducing vascular dementia has good therapeutic action, while to oxidation caused by hypertension
Stress damage has protective effect.The medicine that treatment vascular dementia is prepared for the double-colored golden wave of raw material provides new approach.
A kind of double-colored golden wave active component of marein that contains of the present invention is in treatment vascular dementia medicine is prepared
Purposes, from double-colored golden wave extraction contain Malian glycosides effective part, concrete operations follow these steps to carry out:
A. using double-colored golden wave capitulum as raw material, flowed back 3 times using the 5-20 times of petroleum ether measured micro-boiling, 1 is small every time
When, petroleum ether is discarded, retains double-colored golden wave residue;
B. remaining golden wave residue in step a, the ethanol for being 40-95% with concentration are extracted 2 times, Extracting temperature 60-80
DEG C, solid-liquid ratio 1:5-1:25, obtain total extract;
C. by the total extract that step b is obtained by concentration be 10-95% ethanol dissolve, with macroreticular resin, polyamide or
Glucose gel is adsorbed, the ethanol elution for being 20-90% with concentration, collects eluent, and eluent is concentrated under reduced pressure drying, both
Containing Malian glycosides effective part, with dry product cubage, general flavone content is calculated as 73.5% with rutin, using high performance liquid chromatograph
It is 47.3-56.5mg/g to measure marein content in general flavone, then according to conventional pharmaceutical method be made capsule, granule,
Tablet or pill.
A kind of double-colored golden wave active component of marein that contains of the present invention is in treatment vascular dementia medicine is prepared
Purposes, using correlation pharmacological experiment carry out inside and outside pharmacodynamic evaluation research, illustrate controlling containing Malian glycosides effective part
Treat the medicinal usage in terms of vascular dementia.
Containing the double-colored golden wave active component of marein, with dry product cubage, general flavone content is calculated as 73.5% with rutin,
High performance liquid chromatograph is used to measure in general flavone marein content as 47.3-56.5mg/g.General flavone uses ultraviolet spectrometry light
Degree method determines.Marein uses high effective liquid chromatography for measuring.
The medicinal usage of the present invention for treating vascular dementia as preparation containing Malian glycosides effective part.Pass through experiment
Show, can substantially shorten the escape latency of vascular dementia rats containing Malian glycosides effective part;It is big to improve vascular dementia
Mouse 120s spanning platform numbers;Raise the SOD in cortex, hippocampus, ChAT, AChE activity;MDA contents are reduced, were significantly improved
Human neuroblastoma cells' strain (SH-SY5Y) cell survival rate of hydrogen damage is aoxidized, has and protects neural cytosis;It is and right
Inducing hypertension of vascular dementia etc. has good therapeutic action.
Brief description of the drawings
Fig. 1 is protective effect figure of the present invention to SH-SY5Y neural cell injuries, wherein compared with control group,###P <
0.001;Compared with model group, * P < 0.05, * * * P < 0.001.
Embodiment
Embodiment 1 (prepares granule)
A. using double-colored golden wave capitulum as raw material, flowed back 3 times using the petroleum ether micro-boiling of 5 times of amounts, 1 hour every time,
Petroleum ether is discarded, retains double-colored golden wave residue;
B. by remaining golden wave residue in step a, extracted 2 times with the ethanol that concentration is 65%, 60 DEG C of Extracting temperature, feed liquid
Than 1:5, obtain total extract;
C. the ethanol that total extract concentration step b obtained is 50% dissolves, and with macroporous resin adsorption, is with concentration
40% ethanol elution, eluent is collected, eluent is concentrated under reduced pressure drying, must both contain Malian glycosides effective part, be contained with dry product
Amount calculates, and general flavone content is calculated as 73.5% with rutin, use high performance liquid chromatograph measure in general flavone marein content for
47.3-56.5mg/g, then Malian glycosides effective part will be contained and dried according to a conventional method, obtain containing the dry leaching powder of Malian glycosides effective part,
It will obtain again containing the dry leaching powder of Malian glycosides effective part and dextrin in mass ratio 1:0.75 is well mixed, using concentration as 90% ethanol
Softwood processed, temperature 60 C are dried, and produce granule.
Embodiment 2 (prepares granule)
A. using double-colored golden wave capitulum as raw material, flowed back 3 times using the petroleum ether micro-boiling of 8 times of amounts, 1 hour every time,
Petroleum ether is discarded, retains double-colored golden wave residue;
B. by remaining golden wave residue in step a, extracted 2 times with the ethanol that concentration is 70%, 65 DEG C of Extracting temperature, feed liquid
Than 1:10, obtain total extract;
C. total extract step b obtained dissolves for 50% ethanol by volume, with polycaprolactam, uses concentration
50% ethanol elution, eluent is collected, eluent is concentrated under reduced pressure drying, must both contain Malian glycosides effective part, be contained with dry product
Amount calculates, and general flavone content is calculated as 73.5% with rutin, use high performance liquid chromatograph measure in general flavone marein content for
47.3-56.5mg/g, then Malian glycosides effective part will be contained and dried according to a conventional method, obtain containing the dry leaching powder of Malian glycosides effective part,
It will obtain again containing the dry leaching powder of Malian glycosides effective part and dextrin in mass ratio 1:0.75 is well mixed, using concentration as 90% ethanol
Softwood processed, temperature 60 C are dried, and produce granule.
Embodiment 3 (prepares granule)
A. using double-colored golden wave capitulum as raw material, flowed back 3 times using the petroleum ether micro-boiling of 10 times of amounts, 1 hour every time,
Petroleum ether is discarded, retains double-colored golden wave residue;
B. it is that 80% ethanol extracts 2 times with concentration by remaining golden wave residue in step a, 70 DEG C of Extracting temperature, solid-liquid ratio
1:15, obtain total extract;
C. the total extract that step b is obtained is dissolved by the ethanol that concentration is 50%, with macroporous resin adsorption, uses concentration
50% ethanol elution, eluent is collected, eluent is concentrated under reduced pressure drying, must both contain Malian glycosides effective part, be contained with dry product
Amount calculates, and general flavone content is calculated as 73.5% with rutin, use high performance liquid chromatograph measure in general flavone marein content for
47.3-56.5mg/g, then Malian glycosides effective part will be contained and dried according to a conventional method, obtain containing the dry leaching powder of Malian glycosides effective part,
It will obtain again containing the dry leaching powder of Malian glycosides effective part and dextrin in mass ratio 1:0.75 is well mixed, using concentration as 90% ethanol
Softwood processed, temperature 60 C are dried, and produce granule.
Embodiment 4 (prepares tablet)
A. using double-colored golden wave capitulum as raw material, flowed back 3 times using the petroleum ether micro-boiling of 12 times of amounts, 1 hour every time,
Petroleum ether is discarded, retains double-colored golden wave residue;
B. it is that 70% ethanol extracts 2 times with concentration by remaining golden wave residue in step a, 80 DEG C of Extracting temperature, solid-liquid ratio
1:18, obtain total extract;
C. the total extract that step b is obtained is dissolved by the ethanol that concentration is 55%, with macroporous resin adsorption, uses concentration
60% ethanol elution, eluent is collected, eluent is concentrated under reduced pressure drying, must both contain Malian glycosides effective part, be contained with dry product
Amount calculates, and general flavone content is calculated as 73.5% with rutin, use high performance liquid chromatograph measure in general flavone marein content for
47.3-56.5mg/g, then Malian glycosides effective part will be contained and dried according to a conventional method, obtain containing Malian glycosides effective part dry extract
Powder, then fine powder is broken into containing Malian glycosides effective part dry extract by what is obtained, according to extract powder and starch in mass ratio 8.5:1.5
Supplementary product starch is added, mixes, particle is made, is dried, it is tabletted, film coating, produce tablet.
Embodiment 5 (prepares tablet)
A. using double-colored golden wave capitulum as raw material, flowed back 3 times using the petroleum ether micro-boiling of 15 times of amounts, 1 hour every time,
Petroleum ether is discarded, retains double-colored golden wave residue;
B. it is that 80% ethanol extracts 2 times with concentration by remaining golden wave residue in step a, 60 DEG C of Extracting temperature, solid-liquid ratio
1:18, obtain total extract;
C. the total extract that step b is obtained is dissolved by the ethanol that concentration is 70%, with macroporous resin adsorption, uses concentration
95% ethanol elution, eluent is collected, eluent is concentrated under reduced pressure drying, must both contain Malian glycosides effective part, be contained with dry product
Amount calculates, and general flavone content is calculated as 73.5% with rutin, use high performance liquid chromatograph measure in general flavone marein content for
47.3-56.5mg/g, then Malian glycosides effective part will be contained and dried according to a conventional method, obtain containing Malian glycosides effective part dry extract
Powder, then fine powder is broken into containing Malian glycosides effective part dry extract by what is obtained, according to extract powder and starch in mass ratio 8.5:1.5
Supplementary product starch is added, mixes, particle is made, is dried, it is tabletted, film coating, produce tablet.
Embodiment 6 (prepares tablet)
A. using double-colored golden wave capitulum as raw material, flowed back 3 times using the petroleum ether micro-boiling of 18 times of amounts, 1 hour every time,
Petroleum ether is discarded, retains double-colored golden wave residue;
B. it is that 82% ethanol extracts 2 times with concentration by remaining golden wave residue in step a, 60 DEG C of Extracting temperature, solid-liquid ratio
1:20, obtain total extract;
C. the total extract that step b is obtained is dissolved by the ethanol that concentration is 80%, with polycaprolactam, with concentration 95%
Ethanol elution, collect eluent, eluent be concentrated under reduced pressure drying, must both contain Malian glycosides effective part, with dry product content meter
Calculate, general flavone content is calculated as 73.5% with rutin, uses high performance liquid chromatograph to measure in general flavone marein content as 47.3-
56.5mg/g, then Malian glycosides effective part will be contained and dried according to a conventional method, obtain containing Malian glycosides effective part dry extract, then will
What is obtained is broken into fine powder containing Malian glycosides effective part dry extract, according to extract powder and starch in mass ratio 8.5:1.5 additions are auxiliary
Expect starch, mix, particle is made, dry, it is tabletted, film coating, produce tablet.
Embodiment 7 (prepares tablet)
A. using double-colored golden wave capitulum as raw material, flowed back 3 times using the petroleum ether micro-boiling of 20 times of amounts, 1 hour every time,
Petroleum ether is discarded, retains double-colored golden wave residue;
B. it is that 95% ethanol extracts 2 times with concentration by remaining golden wave residue in step a, 60 DEG C of Extracting temperature, solid-liquid ratio
1:15, obtain total extract;
C. the total extract that step b is obtained is dissolved by the ethanol that concentration is 60%, with polycaprolactam, with concentration 70%
Ethanol elution, collect eluent, eluent be concentrated under reduced pressure drying, must both contain Malian glycosides effective part, with dry product content meter
Calculate, general flavone content is calculated as 73.5% with rutin, uses high performance liquid chromatograph to measure in general flavone marein content as 47.3-
56.5mg/g, then Malian glycosides effective part will be contained and dried according to a conventional method, obtain containing Malian glycosides effective part dry extract, then will
What is obtained is broken into fine powder containing Malian glycosides effective part dry extract, according to extract powder and starch in mass ratio 8.5:1.5 additions are auxiliary
Expect starch, mix, particle is made, dry, it is tabletted, film coating, produce tablet.
Embodiment 8
Influence containing Malian glycosides effective part to vascular dementia (VD) rat behavior:
Healthy female Wistar rats 50, mouse age 4-7 months, body weight 280-350g, Xinjiang Experimental Animal Center provides
And nursing;It is randomly divided into sham-operation group (Normal group), model control group, containing the double-colored golden wave active component group of marein;
Rat 10% chloraldurate (0.35ml/100g) intraperitoneal injection of anesthesia, neck median incision, bilateral common carotid arteries are separated, point
Not Jie Zha bilateral common carotid arteries far and near end, and from centre cut, with ensure block arteria carotis communis blood flow;Sham-operation group is removed and not tied
Prick, do not cut outside bilateral common carotid arteries, remaining process is identical with operation group.The double-colored golden wave active component group containing marein is preoperative
10d and the postoperative daily double-colored golden wave active component group gavage containing marein, common gavage 45d;Sham-operation compares, model comparison
Group rat gives physiological saline 3ml/d, 1 time/d gavage;
The measure of memory function:The survey that Rats With Memory function is carried out using Morris water mazes in the 15th day after modeling
It is fixed;The Experiment Training stage is carried out continuously 4d, daily training 2 times, carries out the orientation navigation experiment training of Morris water mazes, afterwards
Continuous 5d carries out positioning cruise experiment, 2 times a day, calculates average achievement;
5d carries out space exploration experiment, removes platform, and optional 1 place of entry puts into rat in water towards pool wall, record
Rat, across the number of virtual platform, is shown in Table 1, table 2 in 120s;
Table 1.Morris water maze rat orientation navigations result of the test (second,N=10)
Compared with model group, * P < 0.05, * * P < 0.01.
Table 2.Morris water maze rats space exploration result of the test (N=10)
Compared with model group, * P < 0.05, * * P < 0.01.
Result of study shows:Compared with model group, the escape latency of the double-colored golden wave active component group containing marein is bright
Aobvious to shorten, 120s spanning platform numbers are significantly greater than model group.
Embodiment 9
Effect of the double-colored golden wave active component containing marein to vascular dementia (VD) rat oxygen radical:
Put to death and take brain in embodiment 9 after rat, separate hippocampus and cortex, the water-bath that 4 DEG C of temperature is immediately placed on after weighing are even
Device homogenate is starched, centrifuges 150g × 10min, 10% hippocampus, cortical tissue's homogenate is prepared, it is standby to put -20 DEG C of refrigerators of temperature;Examination
Agent box method measure superoxide dismutase (SOD), choline acetyl transferase (ChAT), acetylcholine (AChE) content, specifically
Operation is carried out by kit specification, is shown in Table 3
The double-colored golden wave active component containing marein of table 3 to VD rats SOD, MDA, ChAT, AChE influence (n
=10)
Compared with model group, * P < 0.05, * * P < 0.01
Compared with model group, the superoxide dismutase (SOD) in coreopsis extract group cortex, hippocampus, choline acetyl
Change transferase (ChAT), acetylcholine (AChE) activity rise, MDA (MDA) content declines.Result above prompting is containing Mali
Glycosides golden wave active component has the ability for improving vascular dementia (VD) learning and memory in rats, removes in cortex, hippocampus freely
Base, peroxidatic reaction of lipid ability is reduced, so as to play a part of mitigating oxidative damage, protection neuron.
Embodiment 10
The double-colored golden wave active component containing marein is to H2O2The protective effect of inducing nerve cell damage:
With human neuroblastoma cells' strain (SH-SY5Y) for research object, by MTS (3- (4,5- lutidines-
2- yls) -5- (3- carboxy-- methoxyphenyls) -2- (4- sulfophenyls) -2H- tetrazoliums) colorimetric determination coreopsis extract is to nerve
The protective effect of cell, light absorption value is determined at 490nm wavelength with enzyme-linked immunosorbent assay instrument, pass through the reacting condition gold of light absorption value
Chicken chrysanthemum extract is shown in Fig. 1 to cell survival and the influence of growth;
As a result show, H2O2Damage group cell survival rate is 23.86%;The double-colored golden wave active component containing marein is to 100
μ g/mL groups cell survival rate is 70.16%, with respect to H2O2Damage group survival rate improves 194.01%;Golden wave containing marein has
It is 31.73% to 20 μ g/mL groups cell survival rates to imitate position, with respect to H2O2Damage group survival rate improves 32.96%;Containing Mali
Glycosides golden wave active component is 25.89% to 4 μ g/mL groups cell survival rates, with respect to H2O2Damage group survival rate improves
8.52%.
Embodiment 11
Containing the double-colored golden wave active component Study on antioxidation of marein:
This example uses Kunming mouse 60, male and female half and half, hypertension mouse mould is made using high salt composite frozen legal system
Type, after model success, it is administered using the double-colored golden wave active component containing marein, and set positive control drug captopril
Group, successive administration 30 days, 4 are shown in Table, table 5;
The double-colored golden wave active component containing marein of table 4 is to hypertension mouse SOD in serum, MDA influence
The * P < 0.05 compared with model group, * * P < 0.01.
The double-colored golden wave active component containing marein of table 5 is to hypertension mouse liver SOD, MDA, GSH-Px, T-AOC shadow
Ring (N=10)
Compared with model group, * P < 0.05, * * P < 0.01.
The double-colored golden wave active component containing marein can improve SOD, GSH-Px in blood pressure model group mice serum and liver,
T-AOC vigor, reduction MDA contents are bright, illustrate the oxidative stress to hypertension mouse containing the double-colored golden wave active component of marein
Damage has protective effect, so as to prevent and treat the vascular dementia as caused by hypertension.
Embodiment 12
The antihypertensive effect and study on mechanism of the double-colored golden wave active component containing marein:
Mouse in embodiment 11 is after administration terminates, measure blood pressure, plasma A ng I, plasma A ng II, nephridial tissue Ang II
And serum NO levels, 6 are shown in Table, table 7;
The double-colored golden wave active component containing marein of table 6 to hypertension mouse blood pressure influence (N=10)
Compared with model group, * P<0.05.**P<0.01;Compared with positive controls,#P<0.05.##P<0.01;
The double-colored golden wave active component containing marein of table 7 is to the Ang I of hypertension mouse blood plasma, Ang II, plasma A LD, blood
Starch ET-1 and serum NO level influence (N=10)
Compared with model group, * P < 0.05, * * P < 0.01;
As can be seen from the table:The double-colored golden wave active component containing marein can significantly reduce the blood pressure of hypertension mouse,
It is horizontal to raise plasma angiotensinogen I (Ang I);Reduce plasma angiotensinogen II (Ang II) levels, plasma aldosterone (ALD)
Horizontal, endothelin level 1 (ET-1) level;Improve serum NO levels.It these results suggest that:The double-colored golden wave containing marein is effective
Position has definite therapeutic action to hypertension mouse, so as to prevent and treat the vascular dementia as caused by hypertension.
Claims (1)
1. a kind of purposes containing the double-colored golden wave active component of marein in treatment vascular dementia medicine is prepared, its feature exists
Contain Malian glycosides effective part in being extracted from double-colored golden wave, concrete operations follow these steps to carry out:
A, using double-colored golden wave capitulum as raw material, flowed back 3 times, 1 hour every time, abandoned using the 5-20 times of petroleum ether measured micro-boiling
Petroleum ether is removed, retains double-colored golden wave residue;
B, remaining golden wave residue in step a, the ethanol for being 40-95% with concentration are extracted 2 times, 60-80 DEG C of Extracting temperature, material
Liquor ratio 1:5-1:25, obtain total extract;
C, the total extract that step b is obtained is dissolved by the ethanol that concentration is 10-95%, with macroreticular resin, polyamide or glucose
Gel adsorption, with concentration 20-90% ethanol elution, eluent is collected, eluent is concentrated under reduced pressure drying, must both contain marein
Active component, with dry product cubage, general flavone content is calculated as 73.5% with rutin, and total Huang is measured using high performance liquid chromatograph
Marein content is 47.3-56.5mg/g in ketone, and granule or tablet then is made according to conventional pharmaceutical method.
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