CN1923191A - Use of flavanone kind composition in preparation of medicine for curing cardio vascular diseases - Google Patents

Use of flavanone kind composition in preparation of medicine for curing cardio vascular diseases Download PDF

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CN1923191A
CN1923191A CN 200510093643 CN200510093643A CN1923191A CN 1923191 A CN1923191 A CN 1923191A CN 200510093643 CN200510093643 CN 200510093643 CN 200510093643 A CN200510093643 A CN 200510093643A CN 1923191 A CN1923191 A CN 1923191A
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blu
formula
flavanone
preparation
application
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CN1923191B (en
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赵金华
康晖
姚光辉
曾伟珍
刘小柔
李靖
冯汉林
于琳
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Shenzhen Neptunus Pharmaceutical Co Ltd
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Abstract

The invention discloses the use of dihydroflavonoids compounds having general formula (I) in preparing medicament for preventing and treating cardiovascular diseases, wherein R1 is H or CH3, R2 is H or CH3, R3 is H or OH. The invention also relates to the pharmaceutical compositions containing the dihydroflavonoids compounds, wherein the content of the dihydroflavonoids compounds in each unit of the dose is 5-1000mg.

Description

The application of flavanone kind composition in preparation treatment cardiovascular disease medicine
Technical field
The present invention relates to flavanone kind composition and treat and/or prevent application in the cardiovascular disease medicine in preparation.
The invention still further relates to the pharmaceutical composition that comprises described flavanone kind composition.
Background technology
Herba Blumeae Balsamiferae (Blumea balsamifera (L.) DC) is a feverfew, has another name called Balsamiferou Blumea Herb, Da Ai, sees to be stated from " Guangxi Chinese crude drug standard " (nineteen ninety version).Herba Blumeae Balsamiferae medical material main uses is to extract Borneolum Syntheticum (Borneol), also has minority Chinese medicine compound recipe to be used as medicine with this medical material or its volatile oil.
The preparation that is used as medicine with Herba Blumeae Balsamiferae extract in the prior art, its reactive compound are mainly the Oleum Blumeae Balsamiferae that composition is a terpene substances, as " the upright refreshing drop pill of pharynx ", Jinjian larynx spray, the mould peace Oral preparation of match etc.The bibliographical information relevant with Herba Blumeae Balsamiferae relates generally to plant culture, plant component etc., and pharmaceutical research relates generally to the liver protective effect.The disclosed Chinese patent relevant with Herba Blumeae Balsamiferae extract relates generally to laryngopharyngeal diseases, skin scald, gynaecopathia, as, 200410034599 (promoting blood flow and remove blood stasis and stop bleeding regulating menoxenias); 200410013042,200410013040,200410013041,200410013039,200410016005,03124605,03124594 (gynaecopathia); (97107723.1 treatment oral cavity and laryngopharyngeal diseases), 98112092.X (treatment laryngopharyngeal diseases), 94102037.1 (specially controlling various skin scalds and many places dermatopathy); (951100521.9 treatment hyperosteogeny disease); Other has the disclosed Chinese patent of part to relate to the compound Chinese medicinal preparation of being used as medicine with Herba Blumeae Balsamiferae, as 94114866.1 (treatment burn, scald) etc.In addition, Japan Patent JP62087589 relates to three kinds of contained lactone compound Blumealactones A of Herba Blumeae Balsamiferae, B, C.
Disclose in the Chinese patent application 02134927.4 (CN1403451A) Herba Blumeae Balsamiferae total flavones extract preparation resist myocardial ischemia and blood lipid-lowering medicine in application, but described Herba Blumeae Balsamiferae total flavones extract is an effective ingredient in Chinese, only be as main component (or main functional component) with flavone compound, it is the combination of multiple composition, and described flavone compound is meant and belongs to flavonoid on the structure, flavonols, flavanone, the flavanone alcohols, anthocyan, flavanol compound, two benzene pyrrones, osajin, chalcones, dihydrochalcone-type, the aurones class, the chemical compound of homoisoflavone class etc., and they and monosaccharide or the oligosaccharide glucosides or the other forms of derivant that form, and, the gross weight sum of flavone compound accounts for 25~100% of extract gross weight, so, the Herba Blumeae Balsamiferae total flavones extract of this patent disclosure preparation resist myocardial ischemia and blood lipid-lowering medicine in application be the common effect of multiple flavone extract, this on earth effect is to be produced or multiple chemical compound produces by certain chemical compound? which kind of therapeutical effect does each monomer all have? be still waiting further investigation.
The present invention has furtherd investigate the flavanone kind composition that extracts and has treated and/or prevented application in the cardiovascular disease medicine in preparation from Herba Blumeae Balsamiferae.
Summary of the invention
One object of the present invention is to provide suc as formula the flavanone kind composition shown in (I) and treats and/or prevents application in the cardiovascular disease medicine in preparation, and this compounds can separate from the plant Herba Blumeae Balsamiferae and obtains.
Also purpose of the present invention is to provide the pharmaceutical composition that comprises described flavanone kind composition.
According to an aspect of the present invention, described its structure of flavanone kind composition is shown in general formula (I):
Wherein, R 1Be H or CH 3
R 2Be H or CH 3
R 3Be H or OH.
Above-mentioned formula (I) chemical compound can separate from the plant Herba Blumeae Balsamiferae and obtains, and " Herba Blumeae Balsamiferae " of the present invention is meant feverfew Herba Blumeae Balsamiferae (Blumea balsamifera (L.) DC) plant, and the preferred aerial parts of its plant is as dry stem and leaf.
In the chemical compound shown in the above-mentioned general formula (I), the R in formula (I) 1Be H, R 2Be CH 3, R 3During for OH, the chemical name of described chemical compound is 3,3 ', 5,7-tetrahydroxy-4 '-methoxyl group-flavanone (3,3 ', 5,7-tetrahydroxy-4 '-methoxy-flavanone), with its called after blumeatin A (its English name " blumeatin A " or its English initialism " Blu A "), its structure is suc as formula shown in (II) in the present invention:
Figure A20051009364300061
R in formula (I) 1And R 2Be CH 3, R 3During for OH, the chemical name of described chemical compound is 3,3 ', 5-trihydroxy-4 ', 7-dimethoxy-flavanone (3,3 ', 5-tetrahydroxy-4 ', 7-dimethoxy-flavanone), with its called after blumeatin B (its English name " blumeatin B " or its English initialism " Blu B "), its structure is suc as formula shown in (III) in the present invention:
Figure A20051009364300062
R in formula (I) 1Be CH 3, R 2Be H, R 3During for H, the chemical name of described chemical compound is 3 ', 4 ', 5-trihydroxy-7-methoxyl group-flavanone (3,4 ', 5-tetrahydroxy-7-dimethoxy-flavanone), with its called after Herba Blumeae Balsamiferae third element (its English name " blumeatin C " or its English initialism " Blu C "), its structure is suc as formula shown in (IV) in the present invention:
Flavanone kind composition shown in the above-mentioned general formula (I) can separate acquisition by conventional plant Chemical Decomposition purification technique known in the art from the plant Herba Blumeae Balsamiferae.Those skilled in that art can understand, and these chemical compounds also can obtain by the method for chemosynthesis.
In a specific embodiment of the present invention, the preparation method of described flavanone kind composition comprises the steps:
A, with Herba Blumeae Balsamiferae drying, pulverizing, use alcohol reflux, obtain ethanol extract;
B, with ethanol extract in turn with chloroform and ethyl acetate extraction, obtain chloroform extract and ethyl acetate extract;
C, step B is extract obtained through silica gel chromatographic column chromatography repeatedly separates obtaining the flavanone kind composition shown in the general formula (I).
Described cardiovascular disease mainly comprises and myocardial ischemia and dyslipidemia diseases associated, for example myocardial infarction, angina pectoris, hypertension, arteriosclerosis, hyperlipemia and coronary heart disease etc.
Described coronary heart disease is the abbreviation of coronary atherosclerotic heart disease, also claims ischemic heart desease.Clinical symptoms comprises angina pectoris, arrhythmia, acute myocardial infarction, heart failure and sudden cardiac arrest (sudden death) etc.
Described hyperlipemia comprises former or the hyperlipemia concurrent with other disease.
Pharmacodynamics test shows: the flavanone kind composition shown in the formula (I) has and good resist myocardial ischemia and transfer blood fat; And has the pharmacodynamics synergism between them.
According to also aspect of the present invention, the invention provides a kind of pharmaceutical composition that is used for the treatment of or prevents human diseases, it comprises flavanone kind composition and pharmaceutically acceptable carrier and/or the excipient shown in the general formula (I) of effective therapeutic dose.
Described " effectively therapeutic dose " is meant under this dosage, flavanone kind composition of the present invention can improve or palliate a disease symptom or can suppress or block disease progression.
Pharmaceutical composition of the present invention can be a drug-delivery preparation in the gastrointestinal tract, as oral Preparation etc.Wherein, oral solid formulation can be tablet, capsule, granule, pill, lozenge etc.In these preparations, except that the active component that comprises the present invention, can also choose wantonly and contain pharmaceutically acceptable filler, fluidizer, lubricant, correctives, coloring agent etc.These preparations can also be prepared into slow release or controlled release preparation as required.Oral liquid can be solution, suspension, emulsion, elixir etc.Drug-delivery preparation can also be Sublingual tablet, suppository etc. in the gastrointestinal tract.
The present composition can be the parenteral preparation.These preparations can be solution, suspension, emulsion etc.They can pass through intravenous, subcutaneous, intramuscular administration.
For oral formulations such as tablet, the capsule etc. of the present composition, in active component, the dosage of flavone compound described in its unit dosage forms can be 5~1000mg.Preferably, the dosage of flavone compound described in its unit dosage forms is 30~500mg.It can be administered once and/or several every day, each administration a slice (grain) and/or several pieces (grain).
Compared with prior art, the present invention finds that first the flavanone kind composition monomer has good resisting myocardial ischemia and effect for reducing blood fat, can be used for treating and/or preventing of cardiovascular disease such as coronary heart disease, hyperlipemia, atherosclerosis.
In order to understand essence of the present invention better,, describe in detail but do not limit the present invention below by description to better embodiment of the present invention.
The specific embodiment of invention
The used Herba Blumeae Balsamiferae medical material of the present invention is purchased in medical material company, through being accredited as the dry stem and leaf of feverfew Herba Blumeae Balsamiferae (Blumea balsamifera (L.) DC).Adjuvant that the present invention is used and reagent are commercially available purchase commodity if no special instructions.
The separation and the evaluation of blumeatin A, second element, third element
[embodiment 1]
1, extract and separate:
Herba Blumeae Balsamiferae medical material (dry stem and leaf) 500g, pulverizing, 70% alcohol reflux (7.5L * 2), merge extractive liquid, in turn with chloroform and ethyl acetate extraction, reclaims solvent, and is extract obtained through silica gel chromatographic column chromatography repeatedly.As a result, from ethyl acetate extract, separate obtaining Compound I I, III, from chloroform extract, separate obtaining Compound I I, IV.
2, identify:
Chemical compound 1 (blumeatin A, Blu A): white needle.
Elementary analysis: elementary analysis, C:58.18%; H:5.22% does not contain N, S, X.Empirical formula C 16H 14O 7(theoretical value C:58.28%; H:5.18%; O:36.54%), degree of unsaturation 9.
IR:3451;3413(υO-H,s),2944;2838(υC-H,m),1649;1634(υC=O,s),1361(υC-OH,m),1259(υC-O-C,s),1161,1138(υC-H,s),1086(υC-OH,s),1027,997,975(δC-H,s),839,836,798(δC-H,m),811(δC-H,m),766(δC-H,m).
UV-VIS: with ethanol, three kinds of solvent preparations of 0.1mol/L NaOH, 0.1mol/L HCl sample solution.Determination data is as shown in table 1.
The ultraviolet spectra of table 1 chemical compound 1
Solvent λ(nm) Remarks
Alcoholic solution 205 The E absorption band of fortified phenol
291 The K absorption band that the phenyl ring of chromophore replacement is arranged
0.1mol/LHCl 205 The E absorption band of fortified phenol
220,228 The K absorption band that the phenyl ring of chromophore replacement is arranged
0.1mol/LNaOH 217 The E absorption band of substituted benzene phenates
310 The K absorption band that the phenyl ring of chromophore replacement is arranged
1H-NMR:3.78(3H,s),4.51-4.54(1H,m,),5.03(1H,d,11.2Hz),5.81(1H,d,6.2Hz),5.87(1H,d,1.9Hz),5.92(1H,d,1.9Hz),6.87(1H,d,8.0Hz),6.47(1H,d,7.0Hz),6.94(1H,s),9.08(1,s),10.85(1,s),11.95(1,s);
13C-NMR:71.56(C-3),82.83(C-2),95.02(C-6),96.02(C-8),100.50(C-4),111.71(C-5’),115.10(C-6’),119.26(C-2’),129.73(C-1’),146.20(C-3’),147.98(C-4’),162.52(C-7),163.34(C-9),166.83(C-5),197.78(C-4)。
MS:317(M+1)。
Identify that according to above data this chemical compound is 3,3 ', 5,7-tetrahydroxy-4 '-methoxyl group-flavanone.With its called after blumeatin A (Blumeatin A, Blu A).Its structural formula is:
Chemical compound 2 (blumeatin B, Blu B): white needle-like crystals.
m.p.:180~182℃;
EI-MS:333(M+1);
UV(CH 3OH,λmax,nm):289;
1H?NMR(DMSO,δ):11.82(1H,s,C5-OH);8.91(1H,s,C3’-OH);9.23(1H,s,C3’-OH);6.92(1H,s,C2’);6.91(1H,d,J=8Hz,C6’);6.88(1H,d,J=8Hz,C5’-H);6.09(1H,d,J=2Hz,C8-H);6.06(1H,d,J=2Hz,C6-H);5.74(1H,d,J=2Hz,3-OH);5.06(1H,dd,J=11Hz,J=2Hz,C3-OH);4.52(1H,d,J=11Hz,C3-H)3.78(6H,S,2×OCH 3)。
Identify that according to above data this chemical compound is 3,3 ', 5-trihydroxy-4 ', 7-methoxyl group-flavanone, the present invention is called blumeatin B (Blumeatin B, Blu B).Its structural formula is:
Figure A20051009364300101
Chemical compound 3 (Herba Blumeae Balsamiferae third element, Blu C): white needle-like crystals.
m.p.:218℃;
EI-MS:303(M+1);
UV(CH 3OH,λmax,nm):289;
1H?NMR(DMSO,δ):12.08(1H,s,C5-OH);8.97(1H,s,C4’-OH);8.91(1H,s,C3’-OH);6.88(1H,s,C2’-H);6.74(2H,s,C5’-H,6’-H);6.06(2H,s,C6-H,C8-H);5.43(1H,dd,J=12.5,4Hz,C2-H);3.78(3H,s,OCH 3);3.20(1H,dd,J=17.5,12.5Hz,C3-H);2.71(1H,dd,J=17.5,4Hz,C3-H)。
Identify that according to above data this chemical compound is 3 ', 4 ', 5-trihydroxy-7-methoxyl group-flavanone, the present invention is called Herba Blumeae Balsamiferae third element (Blumeatin C, Blu C).Its structural formula is:
Figure A20051009364300102
Pharmacodynamic experiment
[embodiment 2] Blu A, B, C are to the influence of rat heart muscle ischemia due to the coronary ligation
1, test material:
1) test specimen
Blu A, Blu B, Blu C: spectroscopic pure, all by the method separation and purification of embodiment 1 from the Herba Blumeae Balsamiferae medical material.
2) experimental animal
SD rat: purchase in Guangdong Medical Lab Animal Center
2, test method:
The SD rat, gastric infusion is 3 days continuously, twice of every day.Experiment grouping and each treated animal dosage see Table 7.NS is a normal saline.30min after the last administration with Animal Anesthesia, opens breast knot and pricks coronary artery left side descending branch, record II lead electrocardiogram.It is dirty to core after 2 hours, and the myocardial infarction area size is observed in dyeing.
3, result of the test:
(1) Blu A, B, C are to the Electrocardiographic influence of coronary ligation rat
The result is as shown in table 2.Experimental result shows: Blu A, B, C all have and suppress the effect that the rat ECG ST section raises due to the coronary ligation, illustrate that these test specimens all have myocardial ischemia effect due to the anti-coronary ligation.
Different time points ECG ST section current potential behind the table 2 rat coronary ligation (mV, n=6, X ± SD)
Grouping and administration 5min 10min 30min 60min 120min
NS 10ml/kg * 2/ day 0.24±0.06 0.27±0.05 0.31±0.09 0.32±0.10 0.30±0.08
Blu?A 9mg/kg * 2/ day 0.13±0.07 * 0.15±0.06 ** 0.18±0.06 ** 0.20±0.07 0.17±0.07 *
Blu?B 9mg/kg * 2/ day 0.18±0.05 0.18±0.07 * 0.21±0.07 * 0.19±0.05 * 0.20±0.06 *
Blu?C 9mg/kg * 2/ day 0.14±0.06 * 0.17±0.05 * 0.23±0.09 0.25±0.08 0.22±0.06 *
*P<0.05, *P<0.01 sampling test group and NS group be (t-test) relatively.
(2) Blu A, B, C are to the influence of coronary ligation rat heart muscle infarcted region area
The result is as shown in table 3.Experimental result shows: Blu A, B, C all significantly reduce ischemic necrosis district area, confirm that further these test specimens all have function of resisting myocardial ischemia; Aspect efficacy strength, its strong and weak order with above-mentioned to the Electrocardiographic basically identical that influences, that is, and Blu A, B, C.
Table 3 is respectively organized after the rat coronary artery ligation myocardial infarction region area than (n=6, X ± SD)
Grouping and administration The infarcted region area is than (%)
NS 10ml/kg * 2/ day 35.6±4.9
Blu?A 9mg/kg * 2/ day 24.3±2.7 **
Blu?B 9mg/kg * 2/ day 26.6±3.5 **
Blu?C 9mg/kg * 2/ day 25.7±4.6 **
*(t-test) compared with the NS group in p<0.01
[embodiment 3] Blu A, B, C are to the regulating action of unusual blood fat
1, test material:
Test specimen and experimental animal and source thereof are with embodiment 2.
2, experimental technique:
The SD rat feeds 1 week of normal diet under experimental situation, and the blood sampling of the eye corner of the eyes is surveyed blood fat as normal value.The normal control group is fed normal diet, and high fat matched group is fed high lipid food, and experimental group is fed high lipid food administration simultaneously, and administration is plucked eyeball after 2 weeks and got blood, measures every index.
3, experimental result:
The influence of rat hyperlipidemia is as shown in table 4 due to Blu A, B, the C high lipid food.Experimental result shows: Blu A, B, C all have certain accent blood fat.
Table 4 rat high blood lipid model is respectively organized blood fat reducing experimental result (n=10)
Grouping and administration T-CHOL (mmol/L) Triglyceride (mmol/L) Low density lipoprotein, LDL (mmol/L)
Contrast --- 2.86±0.22 0.82±0.24 0.96±0.16 **
NS 10ml/kg * 2/ day 3.32±0.13 1.20±0.35 1.69±0.37
Blu?A 9mg/kg * 2/ day 3.10±0.32 1.15±0.29 1.40±0.25 *
Blu?B 9mg/kg * 2/ day 2.97±0.29 * 1.23±0.34 1.39±0.26 *
Blu?C 9mg/kg * 2/ day 3.07±0.42 1.09±0.36 1.48±0.21 *
*P<0.05, *P<0.01 sampling test group and blank group be (t-test) relatively
The preparation of drug combination that contains Blu A, B, C
Raw material sources:
Blu A, Blu B, Blu C: spectroscopic pure, all separate purification from the Herba Blumeae Balsamiferae medical material.
The preparation of [embodiment 4] tablet
I, prescription:
Principal agent 60g
Starch 50g
Dextrin 60g
Sucrose 10g
Magnesium stearate 2g
Make 1000
Annotate: the principal agent in the prescription is Blu A or Blu B or Blu C
II, method for making: Blu A or Blu B or Blu C sieve with suitable medicine sieve and mix until the mixture that forms homogeneous with sucrose, starch.Add an amount of water and powder is granulated.After the drying, this granule sieved and with all the other mixed with excipients.Then the gained granule is pressed into the tablet of required form.The tablet of other content can prepare by ratio or the tabletting weight that changes reactive compound and excipient.
The preparation of [embodiment 5] capsule
I, prescription:
Principal agent 60g
Lactose 60g
Dextrin 15g
Starch (120 order) 45g
3%HPMC is an amount of
Make 1000
Annotate: the principal agent in the prescription is Blu A or Blu B or Blu C
II, method for making: Blu A or Blu B or Blu C cross 80 mesh sieves, with starch, lactose, dextrin by equivalent multiplication method mix homogeneously, add the HPMC solution for preparing in advance and make soft material, 20 mesh sieves are granulated, about 30 minutes of 60 ℃ of dryings, 18 mesh sieve granulate, encapsulated.
The preparation of [embodiment 6] injection
I, prescription:
Principal agent 25g
Thimerosal 0.01g
Tween 80 1.5g
Sodium chloride 3g
Sodium carboxymethyl cellulose (30-60cpas) 5g
Water for injection adds to 1000ml
Annotate: the principal agent in the prescription is Blu A or Blu B or Blu C
II, method for making: thimerosal is added in the water for injection of 50% amount, adds sodium carboxymethyl cellulose, and the dissolving back filters with 200 order nylon wires, and is airtight standby.Sodium chloride is dissolved in an amount of water for injection, after No. 4 sintered filter funnel filters, adds preheating thimerosal solution and tween 80 and stirs evenly, and heating makes boiling, add BluA or BluB or BluC, mixing takes out and is chilled to room temperature, adds the injection water and transfers to cumulative volume, sintered filter funnel filters, packing (5ml/ props up), sterilization.
Above detailed description of the present invention does not limit the present invention, and those skilled in the art can make various changes and distortion according to the present invention, only otherwise break away from spirit of the present invention, all should belong to the defined scope of claims of the present invention.

Claims (9)

1, the flavanone kind composition shown in the formula (I) treats and/or prevents application in the cardiovascular disease medicine in preparation
Figure A2005100936430002C1
Wherein, R 1Be H or CH 3
R 2Be H or CH 3
R 3Be H or OH.
2, application as claimed in claim 1 is characterized in that the R in the formula (I) 1Be H, R 2Be CH 3, R 3Be OH; Structure is suc as formula shown in (II):
Figure A2005100936430002C2
3, application as claimed in claim 1 is characterized in that the R in the formula (I) 1And R 2Be CH 3, R 3Be OH; Structure is suc as formula shown in (III):
Figure A2005100936430002C3
4, application as claimed in claim 1 is characterized in that the R in the formula (I) 1Be CH 3, R 2Be H, R 3Be H; Structure is suc as formula shown in (IV):
5, application as claimed in claim 1 is characterized in that described cardiovascular disease comprises myocardial infarction, angina pectoris, hypertension, arteriosclerosis, hyperlipemia and coronary heart disease.
6, application as claimed in claim 1 is characterized in that described flavanone kind composition separates to obtain from plant Herba Blumeae Balsamiferae (Blumea balsamifera (L.) DC).
7, a kind of pharmaceutical composition is characterized in that comprising
Flavanone kind composition shown in the formula (I) of effective therapeutic dose; And
Pharmaceutically acceptable carrier and/or excipient;
Figure A2005100936430003C2
Wherein, R 1Be H or CH 3
R 2Be H or CH 3
R 3Be H or OH.。
8, the described pharmaceutical composition of claim 7, the dosage that it is characterized in that flavanone kind composition described in its unit dosage forms is 5~1000mg.
9, the described pharmaceutical composition of claim 8, the dosage that it is characterized in that flavanone kind composition described in its unit dosage forms is 30~500mg.
CN2005100936436A 2005-08-31 2005-08-31 Use of flavanone kind composition in preparation of medicine for curing cardio vascular diseases Expired - Fee Related CN1923191B (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102973552A (en) * 2012-12-06 2013-03-20 北京中医药大学 Application of blumea balsamifera
CN107515259A (en) * 2017-08-03 2017-12-26 深圳海王医药科技研究院有限公司 The assay method of blumeatin A content in Chinese mugwort heart ketone piece

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1125637C (en) * 2000-07-19 2003-10-29 中山大学 Application of 5,3',5'-trihydroxy-methoxyl dihydroflavone in preparing medicine

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102973552A (en) * 2012-12-06 2013-03-20 北京中医药大学 Application of blumea balsamifera
CN102973552B (en) * 2012-12-06 2015-04-01 北京中医药大学 Application of blumea balsamifera
CN107515259A (en) * 2017-08-03 2017-12-26 深圳海王医药科技研究院有限公司 The assay method of blumeatin A content in Chinese mugwort heart ketone piece

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