CN102336795A - Eucommia ulmoides Oliv active monomer compound and preparation method thereof as well as medicament composition and application thereof - Google Patents
Eucommia ulmoides Oliv active monomer compound and preparation method thereof as well as medicament composition and application thereof Download PDFInfo
- Publication number
- CN102336795A CN102336795A CN2011102036803A CN201110203680A CN102336795A CN 102336795 A CN102336795 A CN 102336795A CN 2011102036803 A CN2011102036803 A CN 2011102036803A CN 201110203680 A CN201110203680 A CN 201110203680A CN 102336795 A CN102336795 A CN 102336795A
- Authority
- CN
- China
- Prior art keywords
- eucommia
- bark
- compound
- oxygen
- reactive monomer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a Eucommia ulmoides Oliv active monomer compound of which the structural formula is shown in the specification, and meanwhile discloses a preparation method of the compound, as well as a medicament composition containing the compound and the medicament application thereof. The active monomer compound is extracted from Eucommia ulmoides Oliv or Eucommia bark, Eucommia leaf, Eucommia male flowers or the whole plant of Eucommia ulmoide Oliv. Proven by the experiment research, the extracted active monomer compound 3-((2S,3S,4S,5S))-4,5-dyhydroxy-6-hydroxymethyl-3-((2S,3S,4S,5R)-3,4,5- tripoly hydroxytetrahydrobiopterin-dihydropyran-2-oxygen)-4-oxygen-dihydropyran-2-oxygen)-2-(3,4- dyhydroxy phenyl)-5,7-dioxo-4'-methoxy-isoflavone has a remarkable nervous excitation effect, small side effects, high safety and can be taken for a long time. The invention provides the Eucommia ulmoides Oliv active monomer compound obtained from the Eucommia ulmoides Oliv and the nervous excitation effect of the compound, so as to provide a new natural active substance for the research and development of the novel central nervous system medicament and health food.
Description
Technical field
The present invention relates to Chinese medicine reactive monomer and preparing technical field thereof, be specifically related to a kind of bark of eucommia reactive monomer compound, preparation method, medical composition and its use.
Background technology
Sensu lato cns (CNS) disease comprises multiple disease, like schizophrenia, dysthymia disorders, epilepsy, Alzheimer's disease, Parkinson's disease, neuropathic pain and multiple sclerosis or the like.So the CNS therapeutical agent is a huge drug type.In recent years, receive the influence of world's financial crisis, various countries' unemployment rate constantly rises; People's stress increases; Cause the sickness rate of Psychiatric disorderses such as anxiety and dysthymia disorders to rise rapidly, global in addition aging population has driven global CNS medicine sales volume and has increased fast.The a data that the internationally famous Frost&Sullivan of consulting firm announces shows; Global cns (CNS) medicine total sales volume was 90,000,000,000 dollars in 2006; And rose to 1,048 hundred million dollars in 2008, account for 1/7 of international then medical market total sales volume.The official of The World Health Organization (WHO) once predicted in 2002, and to the year two thousand twenty, the CNS medicine accounts for 14% of global medical market total amount, and it's 6 years has only been past reality, and promptly 2008, CNS medicine whole world Total sales volume reached this predicted figure in advance.Analyze according to official WHO, developed country and the fast rise of developing country's dysthymia disorders sickness rate and the aggravation of aging population degree at present is two major causes that promote global CNS medicine sales volume surge.Dysthymia disorders has risen to the big Psychiatric disorders of the first in the world at present, so the listing number of anti-depression drug and kind also occupy first of the CNS medicine.The anti-depression drug of global marketing in 2008 has 19,000,000,000～19,100,000,000 dollars approximately.
Weckamine (central nervous system stimulants) is the medicine that can improve the cns functional activity.Various weckamines all can be excited to whole cns, but the maincenter different sites is had selectivity to a certain degree.Weckamine can be divided into analeptic, methyl xanthine class, incitantia.Analeptic commonly used has Nikethamide Nicethamide, diformazan fluorine woods, lobeline, pentetrazole, antiradon, Lrax etc.These drug treating times are generally shorter, and oral the absorption mainly through liver metabolism, is used for treatment by disease or drug-induced respiratory insufficiency and maincenter inhibition.The methyl xanthine class has theine, theophylline, Theobromine etc., its maincenter excitation generally a little less than.Incitantia has amphetamine, Ritalin, pemoline, ephedrine and S-768 etc.
Central excitation medicine commonly used both at home and abroad at present all has certain spinoff and dependency.Low dose can make sleepiness disappear, and fatigue alleviates, and is in high spirits; Resourceful, along with the raising of drug dose not only action intensity increase, and the reach of cns is also enlarged; Cause excitement widely, even cause fainting from fear, also can change inhibition over to because of the exhaustion of energy; Suppress and stupor like excessive convulsions, the nervus centralis of causing of using dosage, severe patient can cause death.Weckamine is mainly used in the central respiratory failure that the antagonism central depressant is poisoned or some transmissible disease causes at present.Their selectivity is generally not high, and safety range is little, and the distance between the dosage of excited respiratory centre and the convulsivant amount is little, and danger is bigger, should strictly grasp dosage during application.Therefore, seek safe and effective medicine more, become the key subjects in the current central excitation medicine research field.
Result of study shows that many traditional Chinese medicine ingredients have good biological activity, and untoward reaction is few, meets medicine from the development trend of non-selectivity to the little direction of efficient, highly selective, spinoff, has broad prospect of application.But traditional Chinese medicine ingredients is complicated; The extraction of active compound, separation, purification difficult; Also need screen highly active compound simultaneously, at present domestic not finding yet has the active monomeric compound of nervous excitation in the Chinese medicine, and efficient, highly selective, the little central excitation series products of spinoff are demanded exploitation urgently.The centering pharmaceutically active ingredient extracts and proves its curative effect through animal experiment, for the modernization of Chinese medicine provides an effective way.
The bark of eucommia (Eucommia ulmoides Oilv.) is the distinctive medicinal plant of China, accounts for 95% of world's total amount, and at present the wild bark of eucommia with plantation in the whole nation reaches 1,000 ten thousand mu according to incompletely statistics, Henan Province wild with more than 100 ten thousand mu of artificial growth areas.Multiple efficacies such as the modern medicine proof bark of eucommia has blood pressure regulation, lowering blood glucose, regulating blood fat, Azelaic Acid, inhibition growth of tumour cell, enriching yin and nourishing kidney, strong muscles and bones, delay senility.In recent years; Existing research shows that Cortex Eucommiae and seed thereof, leaf, flower all have effect to cns; But show as sedative-hypnotic effect always; The concrete activeconstituents and the mechanism of action are not found out as yet yet, up to the present do not see the information that bark of eucommia reactive monomer compound is used in cns effect field as yet.
Summary of the invention
The object of the present invention is to provide a kind of bark of eucommia reactive monomer compound.
The present invention also aims to provide a kind of preparation method of bark of eucommia reactive monomer compound.
The present invention also aims to provide a kind of pharmaceutical composition that contains this bark of eucommia reactive monomer compound.
The present invention also aims to provide a kind of purposes of bark of eucommia reactive monomer compound.
In order to realize above purpose, the technical scheme that the present invention adopted is: a kind of bark of eucommia reactive monomer compound, and the name of this compound is called 3-((2S, 3S; 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S, 3S; 4S, 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3; The 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400, its structural formula is suc as formula shown in the I:
The formula I.
Enantiomorph, tautomer, physiology functional derivatives or the pharmacy acceptable salt of the bark of eucommia reactive monomer compound shown in the formula I.
The preparation method of the bark of eucommia reactive monomer compound shown in the formula I, this compound extracts from the Chinese medicine bark of eucommia and obtains, and its preparation process may further comprise the steps:
(1) systematic solvent extraction leaching process
Get Cortex Eucommiae, Folium Eucommiae, eucommia Bark male flower or bark of eucommia complete stool; The preparation ethanol extract adopts systematic solvent extraction then, and extraction separation is prepared the extract of opposed polarity; Promptly extract said ethanol extract with solvent sherwood oil, ETHYLE ACETATE and propyl carbinol normal temperature successively; The same solvent extract merges afterwards, concentrates, and obtains ligroin extraction, ethyl acetate extract, n-butanol extract respectively;
(2) chromatographic separation process
Said n-butanol extract separates through silica gel column chromatography; The filler that adopts when silica gel column chromatography separates is 100～200 order silica gel, and elutriant is that the volume ratio content of methyl alcohol is 20% chloroform-methanol mixed solution, and the product that wash-out obtains is through concentrating; Carrying out gel column chromatography again separates; The filler of said gel column is Sephadex LH-20, adopts methanol-eluted fractions, obtains bark of eucommia reactive monomer compound.
Wherein the preparation method of ethanol extract is: Cortex Eucommiae, Folium Eucommiae, eucommia Bark male flower or bark of eucommia complete stool are dried in the shade; Pulverize, the use mass percent concentration is 70～95% two weeks of alcohol immersion, then 65 ℃ of recovery soak solutions under vacuum condition; Triplicate, merging obtains ethanol extract.
A kind of pharmaceutical composition that contains the bark of eucommia reactive monomer compound shown in the formula I; Be made up of the bark of eucommia reactive monomer compound shown in the formula I, pharmaceutically acceptable carrier and/or vehicle, this pharmaceutical composition can be processed acceptable any formulation on the pharmaceutics.For example tablet, dispersible tablet, soft capsule, microcapsule, granule, pill, micropill, powder, pill, sustained release preparation, controlled release preparation, stomach and intestine location preparation, oral liquid, injection, powder pin etc.
Further, the weight percentage of bark of eucommia reactive monomer compound in this pharmaceutical composition shown in the formula I is 1%～99%.Preferably, the weight percentage of bark of eucommia reactive monomer compound in this pharmaceutical composition shown in the formula I is 20%～80%.
The application of bark of eucommia reactive monomer compound shown in the formula I in preparation central nervous system stimulant thing and protective foods.
The application of enantiomorph, tautomer, physiology functional derivatives or the pharmacy acceptable salt of the bark of eucommia reactive monomer compound shown in the formula I in preparation central nervous system stimulant thing and protective foods.
Bark of eucommia reactive monomer compound shown in the formula 1 provided by the invention extracts from the bark of eucommia, from Cortex Eucommiae, Folium Eucommiae, eucommia Bark male flower or bark of eucommia complete stool, all can extract to obtain.This reactive monomer compound 3-that extraction obtains ((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3; 4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5; 7-dioxy-4 '-methoxyl group NOVASOY 400 proves to have significant cns excitation through experimental study, and spinoff is less, security is higher.
The stable of dosage guaranteed in the successful extraction preparation of bark of eucommia reactive monomer compound of the present invention, reduced the dose fluctuations that decoction causes.Traditional Chinese medicine all has strict regulation to the place of production, plantation and the collection of medicine, and purpose is exactly to guarantee the quality of medicinal material, still is the stable of effective constituent after all.The bark of eucommia also has other effects such as step-down, anti-inflammatory, and the extraction purifying of nervous excitation reactive monomer compound can be avoided interference and the antagonism between the multiple drug effect.Therefore, confirm and purify in pharmaceutically active ingredient can change traditional method into the more easy control of result accurately to the process control of traditional Chinese medicine quality, and significantly strengthen drug effect, help the modernization of Chinese medicine.
Provided by the invention is active ingredient of Chinese herbs suc as formula the bark of eucommia reactive monomer compound shown in the I, has good promotion cns excitation, and has no side effect and dependency, can take for a long time.The invention provides the reactive monomer compound and the effect of this compound aspect the cns excitement that from the bark of eucommia, obtain, new natural active matter is provided for developing novel healthy food and central nervous system stimulant thing.
Reactive monomer compound provided by the invention can add assistant agent as active constituents of medicine, processes various beverages through modern crafts such as sterilization, tinning, sealings again; Or can become oral liquid through decompression heating (60～70 ℃) evaporation concentration, and also can add the auxiliary material oven dry, auxiliary material can be starch, dextrin etc.; Pulverize the suitable pulvis such as sugar, fruit juice that add in back and process various electuaries; Maybe can add assistant agent, health nutrient meal is processed in sterilization, tinning, sealing, or the electuary form is processed in oven dry.Reactive monomer compound provided by the invention also can be processed medicine material and the conventional pharmaceutical dosage form with cns excitation, like tablet, capsule, granule, oral liquid and injection.
Bark of eucommia reactive monomer compound provided by the invention separates from the bark of eucommia and obtains; Its source is abundant; The stable row that is prone to of the extraction and separation process that adopts, quality controllable, drug effect is sure; To from Chinese medicine, seeking new central nervous system stimulant thing promoter action is arranged, significant to developing of the comprehensive utilization of eucommia resource and bark of eucommia industry.
Description of drawings
Fig. 1 is the mass spectrum of the bark of eucommia reactive monomer compound products that obtains in the embodiment of the invention 1;
Fig. 2 is the H-NMR nuclear magnetic spectrogram of the bark of eucommia reactive monomer compound products that obtains in the embodiment of the invention 1;
Fig. 3 is the C of the bark of eucommia reactive monomer compound products that obtains in the embodiment of the invention 1
13-NMR nuclear magnetic spectrogram.
Embodiment
Embodiment 1
The preparation method of the bark of eucommia reactive monomer compound shown in the formula I, step is following:
(1) systematic solvent extraction leaching process
The Folium Eucommiae harvesting is got wherein 2500g after the cleaning removal of impurities is slightly pulverized after drying in the shade, and the use mass percent is 75% ethanol 30L; Soaked for two weeks, vacuum and low temperature reclaims soak solution (65 ℃, 0.08 mp); Triplicate merges, and obtains ethanol extract; Dry weight 442g adopts systematic solvent extraction then, and extraction separation is prepared the extract of opposed polarity; Concrete grammar is: use each 2000 ml normal temperature ethanol extraction medicinal extract of sherwood oil, ETHYLE ACETATE, propyl carbinol successively, every kind of solvent re-extract four times concentrates each extraction liquid respectively; Obtain all kinds of SOLVENTS medicinal extract, wherein ligroin extraction 29.0g, ethyl acetate extract 50.7g, n-butanol extract 128.2g concentrate surplus water at last and obtain aqueous extract 343.0g;
(2) chromatographic separation process
Bark of eucommia reactive monomer compound shown in the formula I uses the chloroform-methanol volume ratio to be chloroform in the thin-layer chromatography experiment: the developping agent of methyl alcohol=7 ︰ 3 launches, and is the circular point of yellow, and the Rf value is 3;
Get the n-butanol extract 66g that step (1) makes, separate through silica gel column chromatography, the filler of employing is 100～200 order silica gel; Elutriant is that the volume ratio content of methyl alcohol is 20% chloroform-methanol mixed solution, and the product that wash-out obtains separates with gel column chromatography through concentrating again; The filler of gel column is Sephadex LH-20, adopts methanol-eluted fractions, obtains bark of eucommia reactive monomer compound 0.961 g shown in the formula I; For yellow tabular crystal, be soluble in methyl alcohol.Its mass spectrum is seen shown in Figure 1, and the H-NMR nuclear magnetic spectrogram is seen shown in Figure 2, C
13-NMR nuclear magnetic spectrogram is seen shown in Figure 3.Judge that according to Fig. 1, Fig. 2 and Fig. 3 this compound is 3-((2S, 3S, 4S; 5S)-4,5-dihydroxyl-6-methylol-3-((2S, 3S, 4S; 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3; The 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400, its structural formula is:
The formula I.
The biological activity determination of compound shown in the Test Example formula I
1, the excited activity research of cns
1.1 materials and methods
1.1.1 main raw and reagent
The bark of eucommia is taken from bark of eucommia planting base, Wang Ping township, Ruyang County, Luoyang City; Nikethamide Nicethamide, 0.9% sodium chloride solution, Shanghai try a chemical reagent ltd;
1.1.2 key instrument and equipment
GJ-1 type photoelectric counting appearance, Tianjin medicine equipment repair plant;
1.1.3 experimental animal
Kunming kind small white mouse, regular grade, 20～30g (male), University Of Science and Technology Of He'nan experimentation on animals center provides;
1.1.4 TP
1.1.4.1 influence to the mouse autonomic activities
Experiment is divided into groups: 60 of Kunming kind small white mouses are divided into 6 groups, 10 every group at random; The 1st group of negative control group; The 2nd group is formula I active compound low dose group; The 3rd group is following dose groups in the formula I active compound; The 4th group is to go up dose groups in the formula I active compound; The 5th group is formula I active compound high dose group; The 6th group of positive contrast Nikethamide Nicethamide group.Irritate stomach on an empty stomach with saline water for the 1st group, the 2nd group, the 3rd group, the 4th group, the 5th group mice lavage dosage is respectively 50 mgkg
-1Bw
-1, 100 mgkg
-1Bw
-1, 200 mgkg
-1Bw
-1, 400 mgkg
-1Bw
-1, the 6th group of abdominal injection Nikethamide Nicethamide, dosage is 50 mgkg
-1Bw
-1Afterwards each group small white mouse is put into the active box of GJ-1 type photoelectric counting appearance respectively, behind administration 30 min, start the movable number of times that registering instrument writes down small white mouse in 5 min, record is the result see shown in the table 1.
1.1.4.2 the convulsions effect that causes test to mouse
Experiment is divided into groups: 60 of Kunming kind small white mouses are divided into 6 groups, 10 every group at random; The 1st group of negative control group; The 2nd group is formula I active compound low dose group; The 3rd group is following dose groups in the formula I active compound; The 4th group is to go up dose groups in the formula I active compound; The 5th group is formula I active compound high dose group; The 6th group of positive contrast Nikethamide Nicethamide group.Irritate stomach on an empty stomach with saline water for the 1st group, the 2nd group, the 3rd group, the 4th group, the 5th group mice lavage dosage is respectively 50 mgkg
-1Bw
-1, 100 mgkg
-1Bw
-1, 200 mgkg
-1Bw
-1, 400 mgkg
-1Bw
-1, the 6th group of abdominal injection Nikethamide Nicethamide, dosage is 50 mgkg
-1Bw
-1The convulsions incidence of mouse in 30 min after the observation administration, record is the result see shown in the table 2.
1.2 result and analysis
Adopt statistics software SPSS 11.0 to carry out the statistical analysis of data; One-way analysis of variance is used to the result that influences of the autonomic activities number of times of mouse in bark of eucommia reactive monomer compound various dose group filling stomach processing back, and paired samples t check is adopted in the significance of difference analysis of drug group and control group.
1.2.1 influence to the mouse autonomic activities
In the influence test to the mouse autonomic activities, the autonomic activities number of times result of six groups of mouse that record sees shown in the table 1.
That writes down among table 1 1.1.4.1 respectively organizes mouse autonomic activities number of times (x ± s)
Can find out that from table 1 bark of eucommia reactive monomer compound shown in the formula I has significant short cns excitation, irritate stomach low, in down, in go up, the bark of eucommia reactive monomer compound of high four dosage all can make the autonomic activities number of times of mouse increase.Compare with negative control group, in down dose groups mouse autonomic activities number of times increase significantly (P＜0.05); In go up dose groups and high dose group; Mouse autonomic activities number of times is compared increase extremely significantly (P＜0.01) with negative control group; Results of statistical analysis shows; This bark of eucommia reactive monomer compound has significant dosage correlation (P=0.00079) to the influence of mouse autonomic activities, and is suitable with positive control, do not have significant difference.Low dosage in the dosage range mouse autonomic activities number of times be increased to 201 ± 18 with the increase linear increment of dosage by 142 ± 21.This bark of eucommia reactive monomer compound effects effect and its dosage are proportionate.
1.2.2 the convulsions effect that causes to mouse
In the convulsions effect that the causes test to mouse, the convulsions incidence result of six groups of mouse that record sees shown in the table 2.
That writes down among table 2 1.1.4.2 respectively organizes the mice convulsion incidence
Can find out that from table 2 bark of eucommia reactive monomer compound shown in the formula I has and significantly causes the convulsions effect.Irritate stomach low, in down, in go up, the bark of eucommia reactive monomer compound of high four dosage; In 30 min, the convulsions rate that causes of the bark of eucommia reactive monomer compound of low dosage is 20%, compares obvious rising with negative control group; The convulsions incidence of mouse increases with the increase of dosage; Bark of eucommia reactive monomer compound is irritated when going up dosage in the stomach, and the convulsions incidence of mouse reaches 100%, and is suitable with the Nikethamide Nicethamide positive control.The convulsions incidence of mouse descends to some extent during high dosage, is reduced to 40%.Low dosage in the dosage range, the mice convulsion incidence with irritate stomach dosage and be proportionate.
The health herb tea that present embodiment provides, by 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3,4; 5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400, black tea and composite sweetener are formed, wherein 3-((2S, 3S; 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S, 3S, 4S; 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5, the weight percentage of 7-dioxy-4 '-methoxyl group NOVASOY 400 is 3%.
The preparation method of the health herb tea that present embodiment provides: get 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3; 4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400 3 grams; Mix with 50 gram black tea tealeaves, change kibbler over to and be crushed to the 15-30 order, add 47 kilograms of composite sweeteners, the special-purpose papery bubble bag of packing into after mixing well; The overcoat Aluminum-plastic composite bag seals, and every bag of 5-8 gram is processed the present embodiment health herb tea.
The health instant powder that present embodiment provides, by 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3,4; 5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400, fruit juice pulvis and white sugar are formed, wherein 3-((2S, 3S; 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S, 3S, 4S; 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5, the weight percentage of 7-dioxy-4 '-methoxyl group NOVASOY 400 is 1%.
The preparation method of the health instant powder that present embodiment provides: get 3-((2S, 3S, 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S; 3S, 4S, 5R)-3,4; 5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400 1 gram mixes with 50 gram fruit juice pulvis and 49 gram white sugars; Cross 12 mesh sieves, 75 ℃ of oven dry are packaged into bag, process the health instant powder of present embodiment.
The oral liquid that present embodiment provides, by 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3,4; 5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400, water, phenylformic acid and seasonings are formed, wherein 3-((2S, 3S; 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S, 3S, 4S; 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5, the weight percentage of 7-dioxy-4 '-methoxyl group NOVASOY 400 is 20%.
The preparation method of the oral liquid that present embodiment provides: get 3-((2S, 3S, 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S; 3S, 4S, 5R)-3,4; 5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400 20 grams adds 0.5 gram phenylformic acid and 0.5 gram seasonings; Add water to 100 grams then, be sub-packed in afterwards in 5 milliliters of bottles, gland promptly gets the oral liquid of present embodiment.
The tablet that present embodiment provides, by 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3,4; 5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400, starch, Icing Sugar, talcum powder, Magnesium Stearate are formed, wherein 3-((2S, 3S; 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S, 3S, 4S; 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5, the weight percentage of 7-dioxy-4 '-methoxyl group NOVASOY 400 is 80%.
The preparation method of the tablet that present embodiment provides: get 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3; 4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400 4120 grams; With starch 800 grams, Icing Sugar 200 grams, talcum powder 20 grams, Magnesium Stearate 10 grams mix, and mix drying thoroughly, the tablet of pressing cost embodiment.
The capsule that present embodiment provides, by 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3,4; 5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400, starch, dextrin, talcum powder are formed, wherein 3-((2S, 3S; 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S, 3S, 4S; 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5, the weight percentage of 7-dioxy-4 '-methoxyl group NOVASOY 400 is 99%.
The preparation method of the capsule that present embodiment provides: get 3-((2S, 3S, 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S; 3S, 4S, 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3; The 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400 990 grams mix with starch 4 grams, dextrin 4 grams and talcum powder 2 grams, add 70% ethanol and make wetting agent, granulation; Oven dry, whole grain incapsulates, and processes the capsule of present embodiment.
The injection that present embodiment provides, by 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3,4; 5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400, water for injection, phenylcarbinol, tween-80 are formed, wherein 3-((2S, 3S; 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S, 3S, 4S; 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5, the weight percentage of 7-dioxy-4 '-methoxyl group NOVASOY 400 is 5%.
The preparation method of the injection that present embodiment provides: get 3-((2S, 3S, 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S; 3S, 4S, 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3; The 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400 50 grams adds 500 milliliters of injection waters, and 20 milliliters of phenylcarbinols are with thermal treatment half a hour of 10 pounds of pressure; Freezing 24 hours after-filtration add 10 milliliters of tween-80s again, and adding injection water ad pond om is 1000 grams, stirs, filters, clear and bright; Embedding, 100 ℃ of circulation steams were sterilized in 1 hour, promptly processed the injection of present embodiment, supplied intravenous drip to use.
Embodiment 8
The pill that present embodiment provides, by 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3,4; 5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400 and polyoxyethylene glycol are formed, wherein 3-((2S, 3S; 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S, 3S, 4S; 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5, the weight percentage of 7-dioxy-4 '-methoxyl group NOVASOY 400 is 10%.
The preparation method of the pill that present embodiment provides: get 3-((2S, 3S, 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S; 3S, 4S, 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3; The 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400 50 grams takes by weighing polyethylene glycol 6000 (PEG6000) 450 grams afterwards again, is heated to 100 ℃ to fusion, and this moment is with 50 gram 3-((2S; 3S, 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S, 3S; 4S, 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5; 7-dioxy-4 '-methoxyl group NOVASOY 400 joins in the fused polyoxyethylene glycol, stirs the uniform fused solution of preparation, under the constant temperature fused solution is inclined to dripping pill machine liquid container, and dropping liquid is to whiteruss; Cooling forming, the flush away whiteruss, drying promptly gets the pill of present embodiment.
The dispersible tablet that present embodiment provides, by 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3; 4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400, monocalcium phosphate, lactose, N.F,USP MANNITOL, cross-linked second pyrrolidone and Magnesium Stearate are formed; Wherein 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3; 4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5, the weight percentage of 7-dioxy-4 '-methoxyl group NOVASOY 400 is 9%.
The preparation method of the dispersible tablet that present embodiment provides: get 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3; 4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400 5 grams; Mix with monocalcium phosphate 20 grams, lactose 5 grams, N.F,USP MANNITOL 15 grams, cross-linked second pyrrolidone 10 grams and Magnesium Stearate 0.3 gram afterwards, with 70% ethanol system softwood, 20 mesh sieves are granulated, drying; The whole grain of 14 mesh sieves, compressing tablet makes the dispersible tablet of present embodiment.
Embodiment 10
The chewing tablet that present embodiment provides, by 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3,4; 5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400, monocalcium phosphate, lactose, N.F,USP MANNITOL and Magnesium Stearate are formed, wherein 3-((2S, 3S; 4S, 5S)-4,5-dihydroxyl-6-methylol-3-((2S, 3S, 4S; 5R)-3,4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5, the weight percentage of 7-dioxy-4 '-methoxyl group NOVASOY 400 is 16.5%.
The preparation method of the chewing tablet that present embodiment provides: get 3-((2S, 3S, 4S, 5S)-4; 5-dihydroxyl-6-methylol-3-((2S, 3S, 4S, 5R)-3; 4,5-trihydroxy-tetrahydrochysene-dihydropyrane-2-oxygen)-4-oxygen-dihydropyrane-2-oxygen)-2-(3, the 4-dihydroxy phenyl)-5,7-dioxy-4 '-methoxyl group NOVASOY 400 5 grams; Mix with monocalcium phosphate 5 grams, lactose 5 grams, N.F,USP MANNITOL 15 grams, Magnesium Stearate 0.3 gram afterwards, with 70% ethanol system softwood, 20 mesh sieves are granulated, drying; The whole grain of 14 mesh sieves, compressing tablet makes the chewing tablet of present embodiment.
Claims (9)
1. a bark of eucommia reactive monomer compound is characterized in that, the structural formula of this compound is suc as formula shown in the I:
The formula I.
2. the enantiomorph of the described bark of eucommia reactive monomer of claim 1 compound, tautomer, physiology functional derivatives or pharmacy acceptable salt.
3. the preparation method of the described bark of eucommia reactive monomer of claim 1 compound is characterized in that, this compound extracts from the Chinese medicine bark of eucommia and obtains, and its preparation process may further comprise the steps:
(1) systematic solvent extraction leaching process
Get Cortex Eucommiae, Folium Eucommiae, eucommia Bark male flower or bark of eucommia complete stool; The preparation ethanol extract adopts systematic solvent extraction then, and extraction separation is prepared the extract of opposed polarity; Promptly extract said ethanol extract with solvent sherwood oil, ETHYLE ACETATE and propyl carbinol normal temperature successively; The same solvent extract merges afterwards, concentrates, and obtains ligroin extraction, ethyl acetate extract, n-butanol extract respectively;
(2) chromatographic separation process
Said n-butanol extract separates through silica gel column chromatography; The filler that adopts when silica gel column chromatography separates is 100～200 order silica gel, and elutriant is that the volume ratio content of methyl alcohol is 20% chloroform-methanol mixed solution, and the product that wash-out obtains is through concentrating; Carrying out gel column chromatography again separates; The filler of said gel column is Sephadex LH-20, adopts methanol-eluted fractions, obtains bark of eucommia reactive monomer compound.
4. the preparation method of bark of eucommia reactive monomer compound according to claim 3; It is characterized in that the preparation method of ethanol extract is: Cortex Eucommiae, Folium Eucommiae, eucommia Bark male flower or bark of eucommia complete stool are dried in the shade, pulverize; The use mass percent concentration is 70～95% two weeks of alcohol immersion; Then under vacuum condition 65 ℃ reclaim soak solutions, triplicate merges and obtains ethanol extract.
5. pharmaceutical composition that contains the described bark of eucommia reactive monomer of claim 1 compound; It is characterized in that; Be made up of the described bark of eucommia reactive monomer of claim 1 compound, pharmaceutically acceptable carrier and/or vehicle, this pharmaceutical composition can be processed acceptable any formulation on the pharmaceutics.
6. pharmaceutical composition according to claim 5 is characterized in that, the weight percentage of the described bark of eucommia reactive monomer of claim 1 compound in this pharmaceutical composition is 1%～99%.
7. pharmaceutical composition according to claim 6 is characterized in that, the weight percentage of the described bark of eucommia reactive monomer of claim 1 compound in this pharmaceutical composition is 20%～80%.
8. the application of the described bark of eucommia reactive monomer of claim 1 compound in preparation central nervous system stimulant thing and protective foods.
9. the application of the described compound of claim 2 in preparation central nervous system stimulant thing and protective foods.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102036803A CN102336795A (en) | 2011-07-20 | 2011-07-20 | Eucommia ulmoides Oliv active monomer compound and preparation method thereof as well as medicament composition and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102036803A CN102336795A (en) | 2011-07-20 | 2011-07-20 | Eucommia ulmoides Oliv active monomer compound and preparation method thereof as well as medicament composition and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102336795A true CN102336795A (en) | 2012-02-01 |
Family
ID=45512781
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011102036803A Pending CN102336795A (en) | 2011-07-20 | 2011-07-20 | Eucommia ulmoides Oliv active monomer compound and preparation method thereof as well as medicament composition and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102336795A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103819518A (en) * | 2014-03-05 | 2014-05-28 | 吉首大学 | Preparation method for standardized extracts of eucommia ulmoides pinoresinol diglucoside |
| CN113209153A (en) * | 2021-04-30 | 2021-08-06 | 江西普正制药股份有限公司 | Eucommia ulmoides composition, preparation method and application thereof |
| CN115385925A (en) * | 2022-09-08 | 2022-11-25 | 河南大学 | Nitrogen-containing epoxy compound and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20040074249A (en) * | 2003-02-17 | 2004-08-25 | 주식회사 쓰리지케어 | Method for qualifying the leaves of eucommia ulmoides |
| CN101543505A (en) * | 2009-04-29 | 2009-09-30 | 香港科技大学 | Medicine for preventing and treating Alzheimer's disease and preparing method thereof |
-
2011
- 2011-07-20 CN CN2011102036803A patent/CN102336795A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20040074249A (en) * | 2003-02-17 | 2004-08-25 | 주식회사 쓰리지케어 | Method for qualifying the leaves of eucommia ulmoides |
| CN101543505A (en) * | 2009-04-29 | 2009-09-30 | 香港科技大学 | Medicine for preventing and treating Alzheimer's disease and preparing method thereof |
Non-Patent Citations (5)
| Title |
|---|
| CHIKA TAKAMURA: "Studies on the chemical constituents of green leaves of eucommia ulmoides oliv.", 《J NAT MED》 * |
| LI-WEN TIAN,等: "Phloroglucinol Glycosides from the fresh fruits of eucalyptus maideni", 《J. NAT. PROD》 * |
| ROSEMARY F. WEBBY，等: "A flavonol triglycoside from actinidia arguta var. giraldii", 《PHYTOCHEMISTRY》 * |
| 孙兰萍，等: "杜仲黄酮类化合物的研究进展", 《食品工业科技》 * |
| 李春梅，等: "中药黄蜀葵花化学成分的分离与鉴定（II）", 《沈阳药科大学学报》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103819518A (en) * | 2014-03-05 | 2014-05-28 | 吉首大学 | Preparation method for standardized extracts of eucommia ulmoides pinoresinol diglucoside |
| CN113209153A (en) * | 2021-04-30 | 2021-08-06 | 江西普正制药股份有限公司 | Eucommia ulmoides composition, preparation method and application thereof |
| CN115385925A (en) * | 2022-09-08 | 2022-11-25 | 河南大学 | Nitrogen-containing epoxy compound and preparation method and application thereof |
| CN115385925B (en) * | 2022-09-08 | 2023-06-02 | 河南大学 | Nitrogen-containing epoxy compound and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105878322B (en) | It is a kind of to crystallize sunflower disk extract prepared by enzymatic isolation method and preparation method thereof | |
| CN101244110B (en) | Preparation method of Chinese medicine composition with function of releasing fatigue, reinforcing immunity | |
| CN101559092B (en) | Application of eucommia ulmoides extracts | |
| CN101559168B (en) | Pharmaceutical composition for invigorating Qi, tonifying blood and nourishing liver and kidney as well as preparation method and application thereof | |
| CN101961375B (en) | Extractive of Pu'er tea and preparation method thereof | |
| CN103977179B (en) | Medicine substance with anti-dementia effect and preparation method and application thereof | |
| CN1840166A (en) | Modern Chinese medicinal oral liquid of 'Wen Dan Tang' and preparation method thereof | |
| CN102743401B (en) | Application of panaxadiol saponins fraction in preparing medicine for preventing epilepsia | |
| CN101961424B (en) | Pu-erh tea extract and preparation thereof | |
| CN102697781B (en) | Application of trigonelline in preparation of medicament for preventing and treating diabetes and complication thereof | |
| CN102336795A (en) | Eucommia ulmoides Oliv active monomer compound and preparation method thereof as well as medicament composition and application thereof | |
| CN101829224A (en) | Traditional Chinese medicine composition preparation and preparation method and quality control method | |
| CN112618608A (en) | Composition with function of dispelling effects of alcohol and preparation method and application thereof | |
| CN106822331A (en) | To lock application of the lichee bark extract based on shape polymer polyphenol in treatment antihyperuricemic disease drug or health products are prepared | |
| CN102579530A (en) | Preparation method of aralia taibaiensis total saponin having diabetes mellitus resisting effect and medicament | |
| CN104922295A (en) | Blood-nourishing and blood-enriching traditional Chinese medicine composition | |
| CN1548053A (en) | New use of baicalin as medicine for treating anxiety neurosis | |
| CN103830374A (en) | Application of three-leaf glycolipid-removal medicine in hyperuricemia | |
| CN101049435A (en) | Method of preparing nutriment for preventing brain dementia of middle-aged persons and elderly persons | |
| CN107648424A (en) | A kind of preparation method of Lycium-rehmannia preparation | |
| CN107802678A (en) | A kind of scattered preparation method of larynx health | |
| CN103520235A (en) | Plant composition with lipid-lowering function and preparation method and application thereof | |
| CN103666990A (en) | Health-care wine and preparation method thereof | |
| CN102614243A (en) | Method for extracting common macrocarpium fruit total glycoside and application of common macrocarpium fruit total glycoside to preparation of hypoxia tolerant medicines | |
| CN101940318B (en) | Soft capsule with functions of relieving cough, anti-inflammation and reducing blood lipid and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20120201 |