CN104873503B - The preparation method and new medical use of fibrauretine and combinations thereof - Google Patents
The preparation method and new medical use of fibrauretine and combinations thereof Download PDFInfo
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Abstract
Have the function that to prevent and treat senile dementia the invention discloses the fibrauretine and composition extracted from Menispermaceae (Menispermaceae) beauty Calamus (Fibraurea Lour.) plant herba fibraureae recisae (Fibraurea recisa Pierre) and congener, proved through zymetology and zoopery, fibrauretine and composition are respectively provided with the effect for preventing and treating senile dementia well.Further research shows that fibrauretine is active stronger compared with composition, and it is main effective substance to illustrate fibrauretine.
Description
Technical field
The present invention is the fibrauretine on being extracted from herba fibraureae recisae and congener and the combination using fibrauretine as main component
Application of the thing in the medicine with preventing and treating senile dementia is prepared.The pharmaceutical preparation of the medicine is directed to, the invention belongs to medicine
Technical field.
Background technology
Senile dementia be with progressive memory impairment and mental loss, abstract thinking obstacle, language ability is not normal, recognizes
Know that dysfunction, the disturbance of consciousness, self care ability and social activities ability decline the progressive brain even lost and be characterized
Degenerative disease.Its pathogenesis is unclear, is a kind of extremely complex nerve and cellular senescence process.Therefore senile dementia
Prevention and treatment be still a world-famous puzzle at present.Clinical treatment medicine can be divided into directed against amyloid-beta proteinosis medicine at present
Thing, quinoline drug, promote acetylcholine release medicine, Porcine HGF accelerator and medicine for improving brain function etc..List
Or be going into clinical research medicine have acetylcarnitine, tacrine, to tie up that crin, silymarin, eserine, hydrochloric acid more
Donepezil etc..The medicine toxic side effect listed is all larger, so research and development toxic side effect is small, is safely and effectively crazy about in anti-ageing year
Slow-witted medicine is significant.
Herba fibraureae recisae (Fibraurea recisa Pierre) belongs to Menispermaceae (Menispermaceae) beauty's Calamus
(Fibraurea Lour.) plant, its rattan dried are also known as coptis root rattan, huangteng, golden key, colour of loess lotus etc., integrated distribution
In subtropical and tropical zones, it is common in the hill cheuch of height above sea level 180-1000 rice.China is mainly distributed on Yunnan, Guangxi etc.
The state such as ground, the Burma adjoined, Vietnam, Laos, Cambodia is also distributed.Herba fibraureae recisae naturally changes rich in alkaloid, lactone isoreactivity
Compound, it is local ethnic group conventional Chinese medicine and natural dye.Its it is medicinal first appeared in《Compendium of Materia Medica》：" herba fibraureae recisae gives birth to the south of the Five Ridges,
If the shape root of fangji, valgar this rattan of people's informal dress, drinking bout food is poisonous, does not also send out naturally.Smell sweetness and bitterness is put down nontoxic ".It has clearing heat and detoxicating, sharp
The drug effects such as urine, antibacterial, anti-inflammatory, and multi-infection disease can be prevented and treated, such as skin disease, pernicious malaria.Through modern pharmacology
Learning research has shown that its main pharmacodynamics active component is isoquinoline alkaloid：Fibrauretine, jateorrhizine etc., it was loaded into 1977《In
State's pharmacopeia》, cure mainly the infection of the upper respiratory tract, acute tonsillitis, conjunctivitis, gastroenteritis, acute pelvitis of pelvic cavity, vaginitis etc..But arrive
So far, at home and abroad there is not yet the fibrauretine that is extracted from herba fibraureae recisae and the composition using fibrauretine as main component are used for
Prevent and treat the report of senile dementia.The present invention is with a wide range of applications.
The structural formula of fibrauretine (fibrauretin)
The content of the invention
One of the object of the invention is to provide fibrauretine and the composition using fibrauretine as main component is treating and preventing always
Application in dementia disease.Specifically fibrauretine and the composition using fibrauretine as main component is used to prepare preventing and treating old age
The new application of anti-dementia agent.Fibrauretine and composition using fibrauretine as main component show through enzymology, are respectively provided with obvious
The activity of acetylcholine esterase inhibition；Proved through animal experiment, be respectively provided with and significantly improve dementia mice learning and memory function, and energy
SOD activity is significantly improved, reduces MDA content.And study and show, fibrauretine is compared with the combination using fibrauretine as main component
Thing has stronger pharmacological activity.
It is another object of the invention to provide the composition using fibrauretine as main component to prepare with preventing and treating old age
Application in anti-dementia agent, composition mainly contain fibrauretine, jateorrhizine, stephanine, stepharanine alkali and jamaicin.It is more true
That cuts says, fibrauretine accounts for 50-85%, and jateorrhizine accounts for 1-5%, and stephanine accounts for 0.5-4%, and stepharanine alkali accounts for 0.5-3%, small
Bark of a cork tree alkali accounts for 0.2-3%, and the content of total alkaloid is not less than 95% in composition.
The present invention using macroreticular resin separation herba fibraureae recisae alkaloid composition, using normal pressure ODS post separation fibrauretines, does not have first
Have and isolate and purify fibrauretine alkaloid composition using the poisonous organic reagent such as chloroform, benzene, ether, methanol, simply profit
Extracted, resin separation, can largely prepared with acidic ethanol, and it is workable, and the pollution to environment is small, has obvious
Technical progress and innovation.
The outstanding contributions of the present invention are：The present invention it has unexpectedly been discovered that, fibrauretine has very strong preventing and treating old silly
Slow-witted effect.Because the preparation that fibrauretine is primary raw material records the applicating history in Chinese Pharmacopoeia, having had more than 20 years, demonstrate,prove
It is bright without any side effects, so the present invention has superiority of the exploitation into preventing and treating senile dementia new drug.
Another outstanding contributions of the present invention are：The present invention it has unexpectedly been discovered that, fibrauretine and composition have very strong
Preventing and treating senile dementia effect, there is stronger pharmacological activity compared with jamaicin and jateorrhizine, and fibrauretine suppresses second in vitro
The activity of acetylcholinesterase is 20 times of positive control drug Doneppezil Hydrochloride, and herba fibraureae recisae promotor composition suppresses acetylcholine ester in vitro
The activity of enzyme is 14 times of positive control drug Doneppezil Hydrochloride, and the present invention provides a kind of new compound for old dementia patients
And Pharmaceutical composition, there is obvious innovative and applicability, also illustrate that present composition main active is herba fibraureae recisae
Element.
Pharmaceutical preparation present invention also offers fibrauretine and using fibrauretine as the composition of main component.Mainly mouth
Formulation, it is mainly selected from any one of tablet, capsule, pill, granule, supensoid agent, oral formulations.
Preparation method it is a further object of the present invention to provide fibrauretine and fibrauretine for the composition of main component, its
It is characterised by：
(1) herba fibraureae recisae coarse powder is extracted 3 times with the 60-95% alcohol refluxs containing acetic acid or formic acid, and each 2-3 hours, merging carries
Liquid is taken, adds medicine liquid volume 0.1%-1% activated carbons, is stirred, filtering, decompression filtrate recycling ethanol obtains medicinal extract, is dissolved in water, makes
Per 1ml medicinal materials containing 1g, centrifugation, supernatant is taken, by D101 macroreticular resins, first with 3-5 times of resin volume of 5-15% ethanol elutions
Enter, then with 4-6 times of resin volume of 50-90% ethanol elutions, collect ethanol eluate, recycling design, be dried under reduced pressure, that is, be able to Huang
Rattan element is the composition of main component.
(2) take the composition using fibrauretine as main component, dissolved with methanol, by ODS Ordinary pressure chromatographic columns, with acetonitrile-
0.4% phosphoric acid solution is mobile phase, gradient elution, isolated fibrauretine.
In order to realize above technical scheme, the content of fibrauretine determines by the following method：
Chromatographic condition：Chromatographic column:ZORBAX SB C18Post (250mm*4.6mm, 35 μm)；Column temperature：30℃；Mobile phase:Second
Nitrile：0.4% phosphoric acid solution (42:68)；Flow velocity：1.0mL/min, Detection wavelength：345nm；Sample size:10μL.
The preparation of reference substance solution：It is appropriate that precision weighs fibrauretine reference substance, adds methanol to dissolve, constant volume, is made into 0.05mg/
ML solution.
The preparation of need testing solution：Precision weighs composition about 25mg, accurately weighed, puts in 50ml measuring bottles, adds methanol to surpass
Sound dissolving is molten to be settled to scale, and precision measures 1ml and put in 10ml measuring bottles, with methanol constant volume to scale.
Sample introduction determines, and calculates the content of fibrauretine.
The content of total alkaloid is measured by method once：
The preparation of reference substance solution：Precision, which weighs, to be dried to the fibrauretine reference substance 4.05mg of constant weight, puts 100ml volumetric flasks
In, add pH4.0 citric acids-disodium hydrogen phosphate buffer solution, and scale is diluted to, it is 0.0405mg/ml to shake up and produce concentration
Reference substance solution.
The preparation of need testing solution：Present composition 10mg is taken, it is accurately weighed, put in 250ml volumetric flasks, add pH4.0
Citric acid-disodium hydrogen phosphate buffer solution, and scale is diluted to, shake up and produce need testing solution.
Precision draws fibrauretine reference substance solution 1ml and test solution 1.0ml and respectively adds pH4.0 citric acids-disodium hydrogen phosphate
Buffer solution is to 2ml.Add 0.05% bromine grass phenol green solution 1.5ml, chloroform 10ml, shake 3min, after static 0.5h, point take
Chloroform liquid, citric acid-disodium hydrogen phosphate buffer solution 2ml is separately taken to operate gained chloroform liquid as blank solution with method,
Absorbance is determined at 417nm, calculates the content of total alkaloid.
Fibrauretine and using fibrauretine be main component composition (abbreviation composition) have prevention and treatment senile dementia
The effect of disease, these pharmacological actions, it is confirmed by following pharmacodynamics test example.
Fibrauretine and composition using fibrauretine as main component provide by Jilin Academy of Chinese Medicine Sciences；Positive control
Medicine Doneppezil Hydrochloride is manufactured (140322A) by Pharmaceutical Co., Ltd. of health material.Jamaicin and jateorrhizine are purchased from Chinese food medicine
Research institute is examined and determine, acetylcholinesterase produces (>=200U/g) by Shanghai Yuan Ye bio tech ltd.
1st, fibrauretine, using fibrauretine be the composition of main component to inhibiting activity of acetylcholinesterase
The preparation of 0.05M (pH=7.8) Tris-HCl buffer solutions：Precision claims 6.0501g Tris alkali in 1L beakers,
The dissolving of about 800mL distilled water is added, pH meter is connected, is continuously added a little concentrated hydrochloric acid, pH value is determined after being sufficiently stirred, is finally adjusted to
PH=7.80 is then transferred in 1L volumetric flasks, and beaker and glass bar distill water washing 3 times with a little, are together transferred to volumetric flask
In, finally it is settled to 1L.
0.2M Na2HPO4Solution：Claim Na2HPO4·12H2The common 7.164g of O are dissolved in water to 100mL.
0.2M NaH2PO4Solution：Claim NaH2PO4·2H2The common 3.121g of O are dissolved in water to 100mL.
0.1M pH=7.0 PBS：Take 39mL 0.2M NaH2PO4The Na of solution and 61mL0.2M2HPO4, it is sufficiently mixed
As 0.2M PH=7.0 PBS, this liquid is diluted 1 times, as 0.1M pH7.0 PBS.
0.1M pH=8.0 PBS：Take 5.3mL 0.2M NaH2PO4Solution and 94.7mL0.2M Na2HPO4Solution, fill
Divide the PBS that mixing is 0.2M PH=8.0, this liquid is diluted 1 times, as 0.1M pH=8.0 PBS.
The preparation of acetylcholinesterase (AChE) solution：100U acetylcholinesterase is dissolved in 50mL Tris-HCl
In (0.05M, pH=7.8) buffer solution, the 50mg stable enzyme liquid of Bovine serum albumin is added, produces 2U/mL enzyme solutions.
The enzyme liquid that 2U/mL enzyme liquid is diluted to 0.5U/mL with pH=8.0 PBS uses for Ellman methods.
2mM DTNB preparation：3.96mg DTNB are first dissolved with 500 μ L absolute ethyl alcohol, then add 1.5mg NaHCO3, so
Afterwards with pH=7.0 PBS constant volumes to 5mL.
15mM ATCI preparation：21.67mg ATCI add distilled water to dissolve and are settled to 5mL.4 DEG C of refrigerators preserve.
The configuration of Doneppezil Hydrochloride solution：10mg Doneppezil Hydrochloride is dissolved in 5mL pH=8.0 PBS, is filled
Point concussion is made into 2mg/mL solution, then successively with pH=8.0 PBS be diluted to 0.025mg/mL, 0.05mg/mL,
0.1mg/mL, 0.25mg/mL, 0.5mg/mL, 1.0mg/mL stand-by solution.
Treat the configuration of sample measuring liquid：Fibrauretine, composition, jamaicin, jateorrhizine using fibrauretine as main component are taken, accurately
Weigh, it is 2mgmL to be made into concentration with pH=8.0 PBS solution dissolving-1Solution, be then diluted to pH=8.0 PBS
0.001mg/mL, 0.025mg/mL, 0.05mg/mL 0.1mg/mL, 0.25mg/mL, 0.5mg/mL, 1.0mg/mL it is stand-by molten
Liquid.
Sample well：140 μ L PBSs (0.1M, pH=8.0) are added in ELISA Plate aperture, 20 μ L testing samples are molten
Liquid and 15 μ L enzyme solutions, 20min is preserved at 4 DEG C after being well mixed.Take out and add 10 μ L DTNB (2mM) and 10 μ L ATChI
(15mM), absorbance can be read in 405nm after reacting 20min at 37 DEG C.
Sample Background control wells：15 μ L enzyme solutions are replaced with 15 μ L PBSs, and other conditions are constant.
Blank control wells：20 μ L testing sample solutions are replaced with 20 μ L PBSs, and other conditions are constant.
Experimental result is shown in accompanying drawing 1-5.
Fig. 1 is positive control drug acetylcholine esterase inhibition suppression curve figure
Fig. 2 is fibrauretine acetylcholine esterase inhibition suppression curve figure
Fig. 3 is composition acetylcholine esterase inhibition suppression curve figure
Fig. 4 is jamaicin acetylcholine esterase inhibition suppression curve figure
Fig. 5 is jateorrhizine acetylcholine esterase inhibition suppression curve figure
It can be seen from suppression curve, fibrauretine and more compared with positive control drug hydrochloric acid as the composition of main component using fibrauretine
Donepezil has stronger inhibitory activity.The IC of positive control drug Doneppezil Hydrochloride50For 0.091mg/mL, fibrauretine IC50For
0.0037mg/mL, the IC of composition50For 0.0062mg/mL, jamaicin IC50For 0.139mg/mL, the IC of jateorrhizine50For
0.090mg/mL。
Illustrate that the activity of fibrauretine is best, composition takes second place, and jamaicin and jateorrhizine also have certain suppression acetyl courage
The activity of alkali esterase, but activity is mutually far short of what is expected compared with fibrauretine and the present composition.
2nd, fibrauretine and composition are to AlCl3Cause the influence of memory deficits in mice
Mouse 90 is taken, is randomly divided into 9 groups, is grouped by table 1.1st day to the 7th day, physiology was subcutaneously injected in control group daily
Salt solution, remaining each group mouse subcutaneous injection AlCl350mg/kg.Medication group difference continuous gavage is administered 2 weeks.Carry out keeping away dark experiment,
The errors number that mouse in 3min enters darkroom is recorded, with errors number and wrong percentage test Memory result after 24h.Experiment
It the results are shown in Table 1.
Table 1, fibrauretine and composition are to AlCl3Cause the influence (n=10, X ± S) of memory deficits in mice
* compared with normal group, * P<0.05, * * P<0.01；△ compared with model group,△P<0.05,△△P<0.0l
Illustrate fibrauretine metering different from composition to AlCl3Memory disorders are caused to have different degrees of confrontation effect.Subtract
The when young wrong frequency and error generation rate of mouse.Under the conditions of same dose, fibrauretine has preferably activity compared with composition.
Under same dose, jamaicin collection jateorrhizine is poor compared with fibrauretine and composition activity.
3rd, fibrauretine and composition cause the influence of memory deficits in mice to hyoscine
Mouse 90 is taken, is randomly divided into 9 groups, is grouped by table 2.1st day to the 7th day, control group and model group to distilled water,
Remaining each group is administered by table 2.Once a day, continuous 7 days, after last dose 1h, normal group gave physiological saline 0.1ml/10g, its
Remaining each group carries out Jumping test after giving scopolamine hydrobromide 3mg/kg, 10min, trains 3min, test result is carried out after 24h.
It the results are shown in Table 2.
Table 2, fibrauretine and composition cause the influence (n=10, X ± S) of memory deficits in mice to hyoscine
* compared with normal group, * P<0.05, * * P<0.01；△Compared with model group,△P<0.05,△△P<0.0l
Scopolamine hydrobromide group mouse wrong times dramatically increase compared with normal group, and medication group considerably reduces the mistake of mouse
Number by mistake, has obvious antagonism to the memory deficits in mice caused by scopolamine hydrobromide group.Significantly reduce the mistake of mouse
Frequency and error generation rate by mistake.Under the conditions of same dose, fibrauretine has preferably activity compared with composition.In same dose
Under, jamaicin collection jateorrhizine is poor compared with fibrauretine and composition activity.
4th, fibrauretine and composition cause the influence of memory deficits in mice to 30% ethanol
Mouse 90 is taken, is randomly divided into 9 groups, is grouped by table 3.1st day to the 7th day, control group and model group to distilled water,
Remaining each group is administered by table 3.Once a day, continuous 7 days, after last dose 1h, normal group gave physiological saline 0.1ml/10g, its
Remaining each group gives 30% ethanol, carries out Jumping test after 15min, in test record 5min per mouse errors number.As a result see
Table 3.
Table 3, fibrauretine and composition cause the influence (n=10, X ± S) of memory deficits in mice to 30% ethanol
* compared with normal group, * P<0.05, * * P<0.01；△Compared with model group,△P<0.05,△△P<0.0l
30% ethanol group mouse wrong times dramatically increase compared with normal group, and for medication group in addition to low dose of general flavone, remaining is each
Group has obvious antagonism to the memory deficits in mice caused by 30% ethanol.Under the conditions of same dose, fibrauretine is compared with composition
It is stronger to the memory deficits in mice antagonism caused by 30% ethanol.Under same dose, jamaicin collection jateorrhizine is compared with fibrauretine
And composition activity is poor.
5th, fibrauretine and composition are to Senlie dementia model mouse brain SOD2 SOD activity, the third two
The influence of aldehyde (MDA) content and brain coefficient.
Mouse 90 is taken, is randomly divided into Normal group and model group.Model group is to A1C13Solution, starts to press for 70 days
400mg/kg/d gavages, use 2g/L A1C1 always later3Solution is drunk；The distilled water of Normal group gavage equivalent.By model
Group is randomly divided into 8 groups, and as shown in table 4, gastric infusion 60 days, Normal group Model of Dementia group fills the distilled water to measure.Entirely
Experimentation avoids contacting with aluminum products.Mouse is put to death, takes out brain tissue rapidly in ice bath, and is accurately weighed, is determined respectively
SOD, MDA and calculating brain coefficient.Experimental result is shown in Table 4.
Influence (the n of table 4, fibrauretine and composition to Senlie dementia model mouse brain SOD activity, MDA contents and brain coefficient
=10, X ± S)
* compared with normal group, * P<0.05, * * P<0.01；△ compared with model group,△P<0.05,△△P<0.0l
Model control group brain SOD activity reduces, and MDA contents increase, brain coefficient reduces (P<0.05).Compared with model group,
The high, medium and low dosage group SOD activity rise of fibrauretine, MDA contents reduce, and composition is high, middle dose group SOD activity rises, MDA
Content reduces (P<0.05 or P<0.01), illustrate that fibrauretine and composition have obvious antioxidation, improve free radical and exist
Internal excess metabolism.Increase SOD contents, strengthen oxidation resistance, accelerate the removing of free radical, suppress peroxidization, suppression
Peroxidation Product MDA processed produces and removed excessive MDA effect, and fibrauretine is notable to the increase of brain coefficient compared with composition, so as to
Illustrate that there is stronger anti-encephalatrophy.Under same dose, jamaicin collection jateorrhizine compared with fibrauretine and composition activity compared with
Difference.
6th, the influence of fibrauretine and composition to Senlie dementia model acetyl choline content.
Mouse 90 is taken, is randomly divided into Normal group and model group.Model group is to A1C13Solution, starts to press for 70 days
400mg/kg/d gavages, use 2g/L A1C1 always later3Solution is drunk；The distilled water of the appearances such as Normal group gavage.By model
Group is randomly divided into 8 groups, and as shown in table 5, gastric infusion 60 days, Normal group Model of Dementia group is filled with isometric distilled water.
Whole experiment process avoids contacting with aluminum products.Rat sacrificed by decapitation, cranium is opened rapidly and peels off brain tissue (removal cerebellar tissue), is taken
Rinsed in the brain tissue physiological saline of part, remove blood, filter paper is wiped dry, adds cold saline and is put into homogenate tube and is filled in ice bath
Divide and grind, 10% brain homogenate is made, centrifugation, takes supernatant colorimetric method for determining brain tissue enzyme acetylcholine content.Experimental result
It is shown in Table 5.
The influence (n=10, X ± S) of table 5, fibrauretine and composition to Senlie dementia model acetyl choline content
* compared with normal group, * P<0.05, * * P<0.01；△ compared with model group,△P<0.05,△△P<0.0l
Each treatment group and model group compare, and acetyl choline content reduces, and has significant difference.Under same dose, herba fibraureae recisae
Element influences more notable compared with composition on the content of acetylcholine.Under same dose, jamaicin collection jateorrhizine is compared with fibrauretine and group
Compound activity is poor.
The present invention is achieved (confirmation) by examples below
Embodiment
Embodiment 1, composition extraction prepare
Herba fibraureae recisae medicinal material 5kg is ground into coarse powder, is extracted 3 times, 2 hours every time, closed with 70% alcohol reflux containing 2% glacial acetic acid
And extract solution, the activated carbon of medicine liquid volume 0.2% is added, is stirred, filtering, decompression filtrate recycling ethanol obtains medicinal extract, is dissolved in water, makes
Per 1ml medicinal materials containing 1g, centrifuge, take supernatant, by D101 macroreticular resins, first with 10% ethanol elution, 5 times of resin volumes, then use
60% 5 times of ethanol elution resin volume, collect ethanol eluate, recycling design, be dried under reduced pressure, that is, be able to fibrauretine for mainly into
The composition divided.Herba fibraureae recisae cellulose content is in composition
78.5%.The content of total alkaloid is 97.8%.
Embodiment 2, fibrauretine preparation
The composition 100mg using fibrauretine as main component is taken, dissolved with methanol, by ODS Ordinary pressure chromatographic columns, with second
The phosphoric acid solution of nitrile -0.4% (42:68) eluted for mobile phase, merge fibrauretine component, be recrystallized to give fibrauretine.
Claims (3)
- A kind of 1. composition using fibrauretine as main component, it is characterised in that：Fibrauretine accounts for 50- by weight percentage 85%, jateorrhizine accounts for 1-5%, and stephanine accounts for 0.5-4%, and stepharanine alkali accounts for 0.5-3%, and jamaicin accounts for 0.2-3%, combination The content of total alkaloid is not less than 95% in thing.
- 2. the preparation method of composition according to claim 1, it is characterised in that：(1) herba fibraureae recisae coarse powder is extracted 3 times with the 60-95% alcohol refluxs containing acetic acid or formic acid, each 2-3 hours, merges extract solution, Medicine liquid volume 0.1%-1% activated carbons are added, are stirred, filtering, decompression filtrate recycling ethanol obtains medicinal extract, is dissolved in water, and makes every 1ml Medicinal material containing 1g, centrifugation, takes supernatant, by D101 macroreticular resins, is first entered with 3-5 times of resin volume of 5-15% ethanol elutions, then With 4-6 times of resin volume of 50-90% ethanol elutions, ethanol eluate is collected, recycling design, is dried under reduced pressure, that is, is able to fibrauretine For the composition of main component.
- 3. the composition using fibrauretine as main component exists in preparation with the application in preventing and treating medicine for senile dementia, its feature In：Composition mainly contains fibrauretine, jateorrhizine, stephanine, stepharanine alkali, jamaicin.
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| CN106349239A (en) * | 2016-08-25 | 2017-01-25 | 西安天生物技术股份有限公司 | Process method for alcohol extraction of palmatine |
| CN106866653A (en) * | 2017-03-01 | 2017-06-20 | 贵州师范学院 | A kind of preparation method and application of jateorrhizine derivant hydrochloric acid salt |
| CN109125321A (en) * | 2018-10-18 | 2019-01-04 | 何忠梅 | Fibrauretine is preparing the application in prevention and/or treatment anti-parkinson drug, herba fibraureae recisae promotor composition and its preparation method and application |
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| 大孔吸附树脂法富集黄藤生物碱提取物的工艺研究;陈鸿平等;《中药与临床》;20111231;第2卷(第6期);第12-15、21页 * |
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