CN103316088A - Natural pharmaceutical composition - Google Patents
Natural pharmaceutical composition Download PDFInfo
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- CN103316088A CN103316088A CN2013102789737A CN201310278973A CN103316088A CN 103316088 A CN103316088 A CN 103316088A CN 2013102789737 A CN2013102789737 A CN 2013102789737A CN 201310278973 A CN201310278973 A CN 201310278973A CN 103316088 A CN103316088 A CN 103316088A
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Abstract
The invention relates to a natural pharmaceutical composition. The natural pharmaceutical composition is prepared from radish seed and long pepper water decoction and concentration extract, raphanin, ethanol extract of long pepper and piperine in a ratio of (3-6):(3-8):(2-5):(4-6). The composition has great curative effects on cancer chemotherapy-induced diarrhea and meanwhile has a synergistic effect on cancer chemotherapy.
Description
Technical field
The present invention relates to a kind of natural drug composition, relate more specifically to a kind of natural drug composition that is comprised of Semen Raphani Fructus Piperis Longi water boiling concentration extract, raphanin, Fructus Piperis Longi ethanol extraction and piperine, the preparation method of this natural drug composition and this natural drug composition are for the preparation of reducing the cancer chemotherapy induced diarrhea and treatment of cancer being played purposes in the medicine of potentiation.
Background technology
Malignant tumor is current harm humans existence, one of healthy principal disease, and its treatment means comprises operation, chemotherapy, radiotherapy, Chinese medicine, and the effect of chemotherapeutic treatment tumor is particularly outstanding.Chemotherapeutic is the cell toxicant antitumor drug, and no matter alone or unite with the toxicity such as all can cause that the patient suffers from diarrhoea, diarrhoea is again Chemotherapy-induced Diarrhea behind the chemotherapy of tumors.In recent years emerging and applying along with chemotherapeutics such as 5-fluorouracil, taxanes, hydroxy camptothecin, irinotecan, xeloda etc., the incidence rate of Chemotherapy-induced Diarrhea improves year by year, if do not carry out active treatment, easily cause patient's dehydration, malnutrition, serum electrolyte disorder, acid base imbalance etc., it is unfavorable greatly not only the rehabilitation of body to be brought, also bring certain difficulty to CC, therefore effective treatment of Chemotherapy-induced Diarrhea has been become the important component part of tumor patient wholistic therapy.
Chemotherapy-induced Diarrhea is with regard to its clinical manifestation, surely belongs to the Chinese medicine category of " having loose bowels ", and Chinese medicine attracts people's attention for the research of having loose bowels, but there is no at present the Chinese patent medicine that the antagonism cancer chemotherapy has alleviating diarrhoea and potentiation.Therefore, research and develop a kind of high-efficiency low-toxicity, cheap, the natural Chinese medicine that can be used for alleviating the cancer chemotherapy induced diarrhea and playing the chemotherapeutic sensitivity effect that is easy to promote becomes clinical problem demanding prompt solution.
Semen Raphani is the dry mature seed of crucifer Radix Raphani Raphanus sativus L., can be used for being used for the treatment of retention of food and drink, abdominal distention, stagnant dysentery.Fructus Piperis Longi is the green fruit of Piperaceae plant Piper longumI., warming spleen and stomach for dispelling cold, therapeutic method to keep the adverse QI flowing downwards pain relieving.Cure mainly: the disease such as be used for coldness and pain in the epigastrium, vomit, have loose bowels, in recent years, Semen Raphani and Fructus Piperis Longi antitumaous effect are confirmed, the inventor is through research and the experiment of each a large amount of formula proportion, obtained at last optimal drug ratio compositions of the present invention, be the compositions of novelty, and proved that it has fabulous curative effect and can play simultaneously the effect that suppresses tumor the cancer chemotherapy induced diarrhea, has finished the present invention thus.
Summary of the invention
A kind of natural drug composition provided by the invention is made of in the ratio of 3-6:3-8:2-5:4-6 by weight Semen Raphani Fructus Piperis Longi water boiling concentration extract, raphanin, Fructus Piperis Longi ethanol extraction and piperine.
Above-mentioned natural drug composition, wherein the usage ratio of Semen Raphani Fructus Piperis Longi water boiling concentration extract, raphanin, Fructus Piperis Longi ethanol extraction and piperine is 6:8:5:6.
Wherein, Semen Raphani Fructus Piperis Longi water boiling concentration extract, raphanin, Fructus Piperis Longi ethanol extraction can be by well known to a person skilled in the art the conventional method acquisition of purifying, and adopt these compositions that conventional method obtains or the natural drug of the present invention that adopts the commercial one-tenth of buying to be grouped into all can obtain identical curative effect.
Preferably, the preparation method of Semen Raphani Fructus Piperis Longi water boiling concentration extract is in the above-mentioned natural drug composition:
Be 1-6 according to proportion compatibility: 1 gets Semen Raphani, Fructus Piperis Longi, distilled water immersion, and heating decocts 1h, and silk filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating is concentrated, ultrafiltration membrance filter, drying under reduced pressure, and get final product.
The preparation method of raphanin is in the above-mentioned natural drug composition:
Semen Raphani grinds and adds excessive defat with n-hexane, phosphate buffer enzymolysis with pH 7.0, add respectively dichloromethane extraction 3 times, merge solvent, organic solvent is removed in decompression, residue volume fraction 10% dissolve with ethanol solution, n-hexane extraction 3 times is with except degrease, again ethanol is used dichloromethane extraction 3 times mutually, merge solvent, rotary evaporation is removed dichloromethane and be get final product.
Fructus Piperis Longi ethanol extraction preparation method is in the above-mentioned natural drug composition:
Get Fructus Piperis Longi, crushing screening, soak with ethanol is crossed the leaching clear liquor, and residue continues to soak 12h, twice filtrate merged, centrifugal 15 minutes of 3000rpm, separation of supernatant, water bath method is concentrated, and drying under reduced pressure becomes dry extract again, pulverizes, and crosses 100 mesh sieves, and get final product.
Process for preparing piperine is in the above-mentioned natural drug composition:
The Fructus Piperis Longi granule is pulverized, and soak with ethanol is crossed the leaching clear liquor, residue continues to soak 12h, and twice filtrate is merged, and is evaporated to thick, left standstill 1-2 days at the concentrated solution place of letting cool, and separates out piperine, filters to get crude product, the crude product of drying is dissolved in the ether, and 10%KOH solution washing three times is collected ether layer, boil off ether and get the faint yellow solid powder, the gained powder is dissolved in the ethanol, the activated carbon decolorizing recrystallization, and get final product.
The present invention also provides the preferred preparation method of this natural drug composition, comprising:
(1) preparation of Semen Raphani Fructus Piperis Longi water boiling concentration extract
Be 1-6 according to proportion compatibility: 1 gets Semen Raphani, Fructus Piperis Longi, distilled water immersion, and heating decocts 1h, and silk filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating is concentrated, ultrafiltration membrance filter, drying under reduced pressure, and get final product.
(2) preparation of raphanin
Semen Raphani grinds and adds excessive defat with n-hexane, phosphate buffer enzymolysis with pH 7.0, add respectively dichloromethane extraction 3 times, merge solvent, organic solvent is removed in decompression, residue volume fraction 10% dissolve with ethanol solution, n-hexane extraction 3 times is with except degrease, again ethanol is used dichloromethane extraction 3 times mutually, merge solvent, rotary evaporation is removed dichloromethane and be get final product.
(3) Fructus Piperis Longi ethanol extraction preparation
Get Fructus Piperis Longi, crushing screening, soak with ethanol is crossed the leaching clear liquor, and residue continues to soak 12h, twice filtrate merged, centrifugal 15 minutes of 3000rpm, separation of supernatant, water bath method is concentrated, and drying under reduced pressure becomes dry extract again, pulverizes, and crosses 100 mesh sieves, and get final product.
(4) piperine preparation
The Fructus Piperis Longi granule is pulverized, and soak with ethanol is crossed the leaching clear liquor, residue continues to soak 12h, and twice filtrate is merged, and is evaporated to thick, left standstill 1-2 days at the concentrated solution place of letting cool, and separates out piperine, filters to get crude product, the crude product of drying is dissolved in the ether, and 10%KOH solution washing three times is collected ether layer, boil off ether and get the faint yellow solid powder, the gained powder is dissolved in the ethanol, the activated carbon decolorizing recrystallization, and get final product.
(5) choose in proportion Semen Raphani Fructus Piperis Longi water boiling concentration extract, raphanin, Fructus Piperis Longi ethanol extraction and piperine, evenly mix, and get final product.
The preparation method of above-mentioned natural drug composition also comprises: the product that step (5) makes is further made capsule or the tablet that contains natural drug composition 100mg or 200mg specification by the pharmacy means of routine.
The beneficial effect of natural drug composition of the present invention aspect anti-Chemotherapy-induced Diarrhea and inhibition tumor is as follows:
1, natural drug composition of the present invention causes studies show that of diarrhea of mouse model at irinotecan: the diarrhoea reaction for the irinotecan induced mice has obvious antagonism.
2, proved that this natural drug composition can strengthen chemotherapeutics to the inhibitory action of tumor, adopted mouse tumor model, observed this natural drug composition and cyclophosphamide combined to the inhibitory action of mouse interior tumor.Studies show that: this natural drug composition can obviously increase cyclophosphamide for the inhibitory action of tumor.
3, the inventor makes up Semen Raphani Fructus Piperis Longi water boiling concentration extract, raphanin, Fructus Piperis Longi ethanol extraction and piperine originally, and determine consumption proportion between these components by great many of experiments, make said composition bring into play good synergism, obtain unexpected effect.Pass through our repeatedly experimentation, ratio between each component of natural drug composition of the present invention has produced unexpected synergism when 3-6:3-8:2-5:4-6, potentiation is obvious, extraordinary effect is played in side effect, especially especially obvious when the usage ratio of each component is 6:8:5:6, this is that the inventor pays a large amount of creative works by keeping punching and obtains on the paper basis of delivering before, and those of ordinary skills only can't simply obtain this ratio range and optimum amount ratio by disclosed content.
4, this natural drug composition Semen Raphani Fructus Piperis Longi water boiling concentration extract, raphanin, Fructus Piperis Longi ethanol extraction and each component of piperine all can obtain by conventional means, some of them component for example raphanin and piperine also can be buied by commerce, and such compositions itself has and obtains convenient, lower-cost effect.This also is the product that has splendid curative effect and higher industrial practicality concurrently that the inventor obtains by a large amount of creative work sides.
The specific embodiment
Further set forth the preparation of natural drug composition of the present invention below by embodiment and test example, with and the beneficial effect in diarrhea and antitumor, used.
Embodiment
The first step: the preparation of various extracts
(1) preparation of Semen Raphani Fructus Piperis Longi water boiling concentration extract
Be 1-6 according to proportion compatibility: 1 gets Semen Raphani, Fructus Piperis Longi, distilled water immersion, and heating decocts 1h, and silk filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating is concentrated, ultrafiltration membrance filter, drying under reduced pressure, and get final product.
(2) preparation of raphanin
Semen Raphani grinds and adds excessive defat with n-hexane, phosphate buffer enzymolysis with pH 7.0, add respectively dichloromethane extraction 3 times, merge solvent, organic solvent is removed in decompression, residue volume fraction 10% dissolve with ethanol solution, n-hexane extraction 3 times is with except degrease, again ethanol is used dichloromethane extraction 3 times mutually, merge solvent, rotary evaporation is removed dichloromethane and be get final product.
(3) Fructus Piperis Longi ethanol extraction preparation
Get Fructus Piperis Longi, crushing screening, soak with ethanol is crossed the leaching clear liquor, and residue continues to soak 12h, twice filtrate merged, centrifugal 15 minutes of 3000rpm, separation of supernatant, water bath method is concentrated, and drying under reduced pressure becomes dry extract again, pulverizes, and crosses 100 mesh sieves, and get final product.
(4) piperine preparation
The Fructus Piperis Longi granule is pulverized, and soak with ethanol is crossed the leaching clear liquor, residue continues to soak 12h, and twice filtrate is merged, and is evaporated to thick, left standstill 1-2 days at the concentrated solution place of letting cool, and separates out piperine, filters to get crude product, the crude product of drying is dissolved in the ether, and 10%KOH solution washing three times is collected ether layer, boil off ether and get the faint yellow solid powder, the gained powder is dissolved in the ethanol, the activated carbon decolorizing recrystallization, and get final product.
Second step: the preparation of preparation
(1) preparation of natural drug composition capsule preparations of the present invention
Take by weighing respectively Semen Raphani Fructus Piperis Longi water boiling concentration extract 24mg, raphanin 32mg, Fructus Piperis Longi ethanol extraction 20mg and the piperine 24mg of above-mentioned steps preparation, take by weighing simultaneously starch 395mg, magnesium stearate 5mg, evenly mix, be filled to capsule.
(2) preparation of natural drug composition tablet of the present invention
Take by weighing respectively Semen Raphani Fructus Piperis Longi water boiling concentration extract 24mg, raphanin 32mg, Fructus Piperis Longi ethanol extraction 20mg and the piperine 24mg of above-mentioned steps preparation, take by weighing simultaneously starch 295mg, lactose 100mg, evenly mix, with wet granulation, drying, mix with the 5mg magnesium stearate behind the granulate, be pressed into tablet.
Drug effect and pharmacology's data:
Compositions is in following test example: the usage ratio of Semen Raphani Fructus Piperis Longi water boiling concentration extract, raphanin, Fructus Piperis Longi ethanol extraction and piperine is 6:8:5:6.Inventor's compositions that the multiple proportioning combination between 3-6:3-8:2-5:4-6 the time obtains to above-mentioned each composition usage ratio carried out with on identical experiment, find that all the natural drug composition in this amount ranges can obtain good synergism, can play good effect and the treatment of cancer is had potentiation the cancer chemotherapy induced diarrhea.Below be the pharmacodynamics data that preferred embodiment obtains:
Test example 1: the pharmacodynamic study of natural drug composition treatment Chemotherapy-induced Diarrhea effect
1, test material
(1) Semen Raphani, Fructus Piperis Longi is purchased from medical material market.
(2) mice, male, ad lib drinking-water before the experiment.
2, test method:
Mice is divided into 5 groups at random, and 5 every group, the A group is model group, and the B group is Semen Raphani Fructus Piperis Longi water boiling concentration extract 10g.kg
-1(being equivalent to contain the crude drug amount), the C group is raphanin 10g.kg
-1(being equivalent to contain the crude drug amount), D group Fructus Piperis Longi ethanol extraction mixes 10g.kg with piperine in the 5:6 ratio
-1(being equivalent to contain the crude drug amount), the E group is natural drug composition 10g.kg of the present invention
-1(being equivalent to contain the crude drug amount), irinotecan intraperitoneal injection (75mg/kg), continuous 4 days, copies the Chemotherapy-induced Diarrhea model at every day 1 time.B, C, D, E group with corresponding extract gavage 8 days, places metabolic cage with mice continuously, spreads white filter paper at the bottom of the cage observing the stool situation, and observes mice crissum situation and Mus tail fecal pollution situation, and in conjunction with cotton swab stimulation anus defecation, every day, observed and recorded was 2 times.Diarrhoea degree standard scoring is as follows: 0 minute: stool is normal or do not have; 1 minute: laxativeness, stool is visible slight wet soft; 2 minutes: moderate diarrhoea, stool wet and not molding.And there is slight crissum painted; 3 minutes, severe diarrhoea, watery stool is also painted with the severe crissum.
3, experimental result
Compare with model group, natural drug composition group Incidence of Diarrhea of the present invention obviously alleviates.The results are shown in Table 1.
Table 1 present composition is on mice Chemotherapy-induced Diarrhea incidence rate and scoring impact
Annotate: a is equivalent to contain the crude drug amount
Test example 2: the pharmacodynamic study of natural drug composition antitumor action of the present invention
1, experiment material
(1) Kunming mouse, body weight 20 ± 2g, ad lib drinking-water before the experiment, 24h natural light irradiation.
(2) cyclophosphamide, the permanent auspicious medical Pharmacy stock Co., Ltd in Jiangsu product.
2, test method:
To mice S
180The inhibition test of sarcoma growth
Employing was gone down to posterity 5-7 days, and well-grown milky ascites is diluted to tumor cell suspension with an amount of physiological saline solution, and cell number is 10
7/ mL, 5 every group, the right axillary fossa subcutaneous vaccination of every Mus 0.2mL(contains oncocyte 2 * 10
6Individual).The inoculation next day random packet, experimental group natural drug composition of the present invention is divided into (200,100mg/mL) two dosage groups, every Mus gavage 0.5 ml gives cyclophosphamide 10gkg simultaneously
-1D
-1Negative control group gives 0.5 mL distilled water; The positive drug group gives cyclophosphamide 10gkg
-1D
-1, successive administration 10 days.The conventional raising, drinking-water, food is not limit.Drug withdrawal next day, mice all takes off cervical vertebra puts to death, and strips subcutaneous solid tumor tumor piece, weighs, and calculates tumor control rate (%) by following formula:
Tumor control rate=(the average tumor of the matched group average tumor of heavy (C)-experimental group heavy (T))/average tumor of matched group heavy (C)
3, result of the test
Natural drug composition of the present invention is low, high dose group all can strengthen the cyclophosphamide agent with to S
180The effect of inhibition degree, especially the strongest with the high dose group effect.(such as table 2)
Table 2 natural drug composition of the present invention is to S
180The tumor inhibition effect of mice
| Group | Suppression ratio (%) |
| Cyclophosphamide | 31.5 |
| Compositions is low+cyclophosphamide | 38.7 |
| Height+cyclophosphamide | 46.1 |
Claims (5)
1. one kind is reduced the cancer chemotherapy induced diarrhea and the treatment cancer is played the natural drug composition of potentiation, it is characterized in that said composition is made of in the ratio of 3-6:3-8:2-5:4-6 by weight Semen Raphani Fructus Piperis Longi water boiling concentration extract, raphanin, Fructus Piperis Longi ethanol extraction and piperine
Wherein the preparation method of Semen Raphani Fructus Piperis Longi water boiling concentration extract is:
Be 1-6 according to proportion compatibility: 1 gets Semen Raphani, Fructus Piperis Longi, distilled water immersion, and heating decocts 1h, and silk filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating is concentrated, ultrafiltration membrance filter, drying under reduced pressure, and get final product;
Wherein the preparation method of raphanin is:
Semen Raphani grinds and adds excessive defat with n-hexane, phosphate buffer enzymolysis with pH 7.0, add respectively dichloromethane extraction 3 times, merge solvent, organic solvent is removed in decompression, residue volume fraction 10% dissolve with ethanol solution, n-hexane extraction 3 times is with except degrease, again ethanol is used dichloromethane extraction 3 times mutually, merge solvent, rotary evaporation is removed dichloromethane and be get final product;
Wherein the preparation method of Fructus Piperis Longi ethanol extraction is:
Get Fructus Piperis Longi, crushing screening, soak with ethanol is crossed the leaching clear liquor, and residue continues to soak 12h, twice filtrate merged, centrifugal 15 minutes of 3000rpm, separation of supernatant, water bath method is concentrated, and drying under reduced pressure becomes dry extract again, pulverizes, and crosses 100 mesh sieves, and get final product;
Wherein the preparation method of piperine is:
The Fructus Piperis Longi granule is pulverized, and soak with ethanol is crossed the leaching clear liquor, residue continues to soak 12h, and twice filtrate is merged, and is evaporated to thick, left standstill 1-2 days at the concentrated solution place of letting cool, and separates out piperine, filters to get crude product, the crude product of drying is dissolved in the ether, and 10%KOH solution washing three times is collected ether layer, boil off ether and get the faint yellow solid powder, the gained powder is dissolved in the ethanol, the activated carbon decolorizing recrystallization, and get final product.
2. natural drug composition as claimed in claim 1, wherein the usage ratio of Semen Raphani Fructus Piperis Longi water boiling concentration extract, raphanin, Fructus Piperis Longi ethanol extraction and piperine is 6:8:5:6.
3. such as the preparation method of the natural drug composition of claim 1 or 2, it is characterized in that the method comprises:
(1) preparation of Semen Raphani Fructus Piperis Longi water boiling concentration extract
Be 1-6 according to proportion compatibility: 1 gets Semen Raphani, Fructus Piperis Longi, distilled water immersion, and heating decocts 1h, and silk filters, and medicinal residues are adding distil water again, soaks, decocts, filters with method, and twice filtrate is mixed, and heating is concentrated, ultrafiltration membrance filter, drying under reduced pressure, and get final product;
(2) preparation of raphanin
Semen Raphani grinds and adds excessive defat with n-hexane, phosphate buffer enzymolysis with pH 7.0, add respectively dichloromethane extraction 3 times, merge solvent, organic solvent is removed in decompression, residue volume fraction 10% dissolve with ethanol solution, n-hexane extraction 3 times is with except degrease, again ethanol is used dichloromethane extraction 3 times mutually, merge solvent, rotary evaporation is removed dichloromethane and be get final product;
(3) preparation of Fructus Piperis Longi ethanol extraction
Get Fructus Piperis Longi, crushing screening, soak with ethanol is crossed the leaching clear liquor, and residue continues to soak 12h, twice filtrate merged, centrifugal 15 minutes of 3000rpm, separation of supernatant, water bath method is concentrated, and drying under reduced pressure becomes dry extract again, pulverizes, and crosses 100 mesh sieves, and get final product;
(4) preparation of piperine
The Fructus Piperis Longi granule is pulverized, and soak with ethanol is crossed the leaching clear liquor, residue continues to soak 12h, and twice filtrate is merged, and is evaporated to thick, left standstill 1-2 days at the concentrated solution place of letting cool, and separates out piperine, filters to get crude product, the crude product of drying is dissolved in the ether, and 10%KOH solution washing three times is collected ether layer, boil off ether and get the faint yellow solid powder, the gained powder is dissolved in the ethanol, the activated carbon decolorizing recrystallization, and get final product;
(5) choosing in proportion Semen Raphani Fructus Piperis Longi water boiling concentration extract, raphanin, Fructus Piperis Longi ethanol extraction evenly mixes with piperine, and get final product.
4. the preparation method of natural drug composition as claimed in claim 3 also comprises: the product that step (5) makes is further made capsule or the tablet that contains natural drug composition 100mg or 200mg specification by the pharmacy means of routine.
5. such as the purposes of each described natural drug composition of claim 1-2 in preparing the medicine that reduces the reaction of cancer chemotherapy induced diarrhea and the treatment cancer is played potentiation.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103768122A (en) * | 2014-02-13 | 2014-05-07 | 山东中医药大学 | Method for extracting total thioglycosides from Raphanus sativus seeds |
| CN103768121A (en) * | 2014-02-13 | 2014-05-07 | 山东中医药大学 | Method for extracting sinapine extract from Raphanus sativus seeds |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103182016A (en) * | 2013-03-27 | 2013-07-03 | 张宗升 | Traditional chinese medicine composition and preparation method thereof |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103182016A (en) * | 2013-03-27 | 2013-07-03 | 张宗升 | Traditional chinese medicine composition and preparation method thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103768122A (en) * | 2014-02-13 | 2014-05-07 | 山东中医药大学 | Method for extracting total thioglycosides from Raphanus sativus seeds |
| CN103768121A (en) * | 2014-02-13 | 2014-05-07 | 山东中医药大学 | Method for extracting sinapine extract from Raphanus sativus seeds |
| CN103768122B (en) * | 2014-02-13 | 2015-11-11 | 山东中医药大学 | A kind of method extracting total sulfur glycosides position from Semen Raphani |
| CN103768121B (en) * | 2014-02-13 | 2015-11-11 | 山东中医药大学 | A kind of method extracting sinapic acid choline ester. extract from Semen Raphani |
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Application publication date: 20130925 |