CN101376653A - Flavonol compound, and preparation and use thereof - Google Patents
Flavonol compound, and preparation and use thereof Download PDFInfo
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- CN101376653A CN101376653A CNA2008102334285A CN200810233428A CN101376653A CN 101376653 A CN101376653 A CN 101376653A CN A2008102334285 A CNA2008102334285 A CN A2008102334285A CN 200810233428 A CN200810233428 A CN 200810233428A CN 101376653 A CN101376653 A CN 101376653A
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- flavonol
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- -1 Flavonol compound Chemical class 0.000 title claims abstract description 32
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Natural products O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 235000011957 flavonols Nutrition 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract 4
- 230000001741 anti-phlogistic effect Effects 0.000 claims abstract 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 39
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- 238000000605 extraction Methods 0.000 claims description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
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Abstract
The invention provides a flavonol compound, and also relates to a preparation method thereof, a pharmaceutical composition comprising the same as the active component, and the application of the compound and the pharmaceutical composition on the preparation of antiphlogistic. The compound has remarkable anti-inflammatory effect, and can be expected to be antiphlogistic. The provided flavonol compound has a structure formula as above.
Description
Technical field
The present invention relates to a kind of flavonol compound---2 ＂-hydroxyl-3 ＂-alkene-dehydration Icaritin, and the preparation method of this compound and be the pharmaceutical composition of activeconstituents, and the application in treatment inflammation medicine with this compound.
Background technology
In recent years, in the research of anti inflammatory immunity medicine, Chinese medicine reaches characteristics such as aboundresources less because of its good drug efficacy, untoward reaction, more and more be subject to people's attention.The anti inflammatory immunity medicine is meant inflammatory reaction inhibited, immune response is had a class medicine of inhibition or enhancing and regulating effect.The immunity system of body is the network system of a complexity, the change of immune certain index often causes the variation of other indexs of body immune system, the anti inflammatory immunity pharmacology has been deep into cell levels and gene level, comprises researchs such as second messenger, nf in cytokine and acceptor thereof, lipoids inflammatory mediator, nitrogen protoxide, active oxygen, the cell.Along with improving constantly of anti-inflammatory pharmacological research method, the especially widespread use of Protocols in Molecular Biology in Chinese medicine anti-inflammatory pharmacological research, researching and developing the new natural drug activeconstituents with anti-inflammatory activity becomes focus gradually.Chinese medicine with antiinflammatory immunity function relates to multiple natural phant kind, as trypterygine, Stem of Orientoine, the coptis, Chinese herbaceous peony, the Radix Astragali, glossy ganoderma, Herba Epimedii etc., activeconstituents relates to polysaccharide, glycosides, alkaloid, lactone, steroidal, tonka bean camphor, anthraquinone, flavones, tannin, volatilization wet goods.
It is found that flavonoid compound has effects such as anti-inflammatory, antiviral, cholagogic, cardiac stimulant, calmness and analgesia the end of the sixties, found again afterwards that it had anti-oxidant, anti-ageing, immunomodulatory and effect such as antitumor.Herba Epimedii total flavones to Oleum Tiglii induced mice ear swelling, acetic acid induced mice abdominal cavity capillary permeability increase, meat Ya hamartoplasia has remarkable restraining effect due to the foot swelling of carrageenin induced mice and the Oleum Tiglii, and primary foot swelling and the Secondary cases foot swelling of adjuvant arthritis rat all had remarkable restraining effect.
Up to now, do not have the report of the flavonol compound 2 ＂-hydroxyl-3 ＂-alkene-dehydration Icaritin of novel structure of the present invention in the prior art, also not this compound as effective ingredient in the relevant report of treatment aspect the disease.
Summary of the invention
The object of the present invention is to provide a kind of new flavonol compound with pharmaceutical use.
Another object of the present invention provides a kind of preparation method of flavonol compound.
It is the pharmaceutical composition of activeconstituents with the flavonol compound that further aim of the present invention provides a kind of.
Another purpose of the present invention provides above-mentioned flavonol compound or the purposes of composition in preparation anti inflammatory immunity medicine.
Inventors of the present invention isolate a kind of new from dry Herba Epimedii (Epimedium brevicornum Maxim) herb, have multiple valuable drug activity, and these activity are that existing Herba Epimedii plant milk extract is not available.
Flavonol compound provided by the invention has following structural formula:
Flavonol compound provided by the invention is extraction separation from the Herba Epimedii herb, and this method may further comprise the steps:
A, dry Herba Epimedii herb pulverized after, press Herba Epimedii: the mass/volume ratio of aqueous acetone solution=1: 2～4, it is 75% aqueous acetone solution that Herba Epimedii is put into concentration, after soaking 15～30 hours under the room temperature, get extracting solution, so repeat to extract united extraction liquid 2～3 times;
B, with the underpressure distillation of above-mentioned A step gained extracting solution after do not have acetone flavor, press extracting solution: the volume ratio of sherwood oil=1: 1, under room temperature, extracting solution is carried out 2～3 times extraction with sherwood oil, reclaim sherwood oil after, must extraction liquid;
C, press extraction liquid: the volume ratio of ethyl acetate=1: 1, under room temperature, the extraction liquid of above-mentioned B step is carried out 2～3 times extraction with ethyl acetate, after the recovery ethyl acetate medicinal extract;
D, silicagel column on the ethyl acetate medicinal extract of above-mentioned C step is carried out chromatographic separation, use chloroform: methyl alcohol=40～0: the mixture of 1 volume ratio carries out wash-out as eluent, remove impurity after, the roughing out thing;
E, the roughing out thing of above-mentioned D step is carried out the silica gel column chromatography identical with step D and wash-out 2～5 times, remove impurity after, smart isolate;
F, the smart isolate of E step gained analyzed with efficient liquid phase chromatographic analysis instrument of the prior art after, with getting flavonol compound after the ZORBAX SB-C18 post of the prior art half preparation separation.
Described flavonol compound is a yellow powder, and its molecular formula is C
21H
20O
7, degree of unsaturation is 12, structure is: and 3,5,7-trihydroxy--8-(2 ＂-hydroxyl-3 ＂-methyl-3 ＂-butenyl)-4 '-methoxy flavone is 2 ＂-hydroxyl-3 ＂-alkene-dehydration Icaritin, and its structural formula is as follows:
The flavonol compound of structural formula provided by the invention (1) is used the test of MTT detection method and is shown after it is to RAW264.7 cytosis 24h do not have the significant cytotoxicity effect, illustrates that the cytotoxicity of flavonol compound is lower.
The flavonol compound of structural formula provided by the invention (1), find that through experimental study it is the TNF-α of the adjusting LPS inductive RAW264.7 emiocytosis of concentration dependent, and can significantly improve the IL-10 level, IL-10 can suppress the synthetic of TNF-α, illustrates that flavonol compound of the present invention has tangible antiinflammatory immunity function.
Pharmaceutical composition provided by the invention contain the said structure formula (1) for the treatment of significant quantity compound activeconstituents and contain one or more pharmaceutically acceptable carrier or auxiliary materials.
Described pharmaceutically acceptable carrier or auxiliary material are meant the pharmaceutical carrier or the auxiliary material of pharmaceutical field routine, as: thinners such as water or alcohol, vehicle, perhaps starch, weighting agents such as sucrose, perhaps derivatived cellulose, alginate, tackiness agent such as gelatin or polyvinylpyrrolidone, perhaps wetting agent such as glycerine, perhaps agar, disintegrating agent such as lime carbonate or sodium bicarbonate, perhaps absorption enhancer such as quaternary ammonium compound, perhaps tensio-active agent such as cetyl alcohol, perhaps absorption carrier such as bentonite or kaolin, perhaps talcum powder, calcium stearate and Magnesium Stearate, lubricants such as polyoxyethylene glycol can add flavouring agent in addition in composition, other assistant agent such as sweeting agent.
The compounds of this invention can composition form by oral, snuffing is gone into, the mode of rectum or administered parenterally need to be applied to the patient of this treatment.Be used for when oral, can be made into conventional solid preparation such as tablet, pulvis, granula, capsule etc., perhaps make the suspension agent of the water of liquid or oil or other syrup, elixir; When being used for administered parenterally, can be made into injection solution, water or oil-suspending agent.Preferred form is tablet, capsule, suppository, nasal spray or injection.
The various formulations of pharmaceutical composition of the present invention can be according to the conventional production method preparation of pharmaceutical field.After for example making activeconstituents and one or more carriers or auxiliary material mixing, make required formulation according to a conventional method.
It is 0.1～99.5% activeconstituents that pharmaceutical composition of the present invention preferably contains mass ratio, and the best mass ratio that preferably contains is 0.5～95% activeconstituents.
The amount of application of The compounds of this invention can change concrete definite according to route of administration, patient age, body weight, the disease type of being treated and severity etc., and its per daily dose can be 0.01～10mg/kg body weight, preferred 0.1～5mg/kg body weight.Can use by one or many.
Description of drawings
Fig. 1 is the HMBC figure of 2 ＂-hydroxyl-3 ＂-alkene-dehydration Icaritin (1);
Fig. 2 is the toxic action of 1 pair of RAW264.7 scavenger cell of compound, and data are represented in Mean ± SEM mode;
Fig. 3 is 1 pair of external LPS inductive RAW264.7 scavenger cell of compound-monocyte TNF-α synthetic influence;
Fig. 4 is the influence of 1 pair of LPS inductive of compound RAW264.7 cell IL-10 synthetic;
Fig. 5 is the process flow sheet of the embodiment of the invention 1.
Embodiment
Below by embodiment the present invention is described further, makes those skilled in the art understand the present invention more comprehensively, but do not limit the present invention in any way.
Flavonol compound i.e. 2 ＂-hydroxyl-3 ＂-alkene-dehydration Icaritin, or 3,5, the preparation of 7-trihydroxy--8-(2 ＂-hydroxyl-3 ＂-methyl-3 ＂-butenyl)-4 '-methoxy flavone:
After getting dry Herba Epimedii (Epimedium brevicornum Maxim) herb 12kg pulverizing, press Herba Epimedii: the mass/volume ratio of aqueous acetone solution=1: 3, with concentration is lixiviate 3 times under the 75% acetone hydroecium temperature, each acetone water consumption is 35L, soak time 24 hours, after merging No. 3 extracting solutions, underpressure distillation is to there being the acetone flavor; Press extracting solution: the volume ratio of sherwood oil=1: 1, earlier with sherwood oil under room temperature to extracting solution extraction three times, each sherwood oil consumption 10L, reclaim sherwood oil after, extraction liquid; Press extraction liquid: the volume ratio of ethyl acetate=1: 1, again with ethyl acetate under room temperature to extraction liquid extraction three times, each ethyl acetate consumption 8L, ethyl acetate medicinal extract 178g; After ethyl acetate medicinal extract granularity is 100-200 purpose 400g silica gel mixed samples, last silicagel column carries out the chromatography roughing out, and silicagel column is equipped with 2kg (granularity is 200-300 orders) silica gel in being, volume is the glass steel silicagel column of 120 * 1500mm, and use chloroform afterwards: methyl alcohol is respectively: 40: 1,20: 1,10: 1,8: 1,5: 1,4: 1, seven eluents of 0: 1 (volume ratio), the chromatographic separation thing carried out wash-out after, separate obtaining 7 roughing out things;
With chloroform: the isolate 20g of the eluent wash-out of methyl alcohol=8: 1 volume ratio with silica gel mixed sample after, last silicagel column (300g silica gel) chromatography, through chloroform: the eluent of methyl alcohol=100: 1 volume ratio carries out wash-out and obtains the 204.4mg isolate, this isolate is gone up silica gel column chromatography (0.2g silica gel mixed sample once more, last 6g silicagel column), and use chloroform: behind the eluent wash-out of methyl alcohol=120: 1 volume ratio, the smart isolate of 26.6mg; Should the essence isolate analyze that (moving phase is 70% methanol through Agilent 1200 HPLC of the prior art (high performance liquid chromatography), 40 ℃ of column temperatures, residence time t=8.2min) after, with ZORBAX SB-C18 post of the prior art half preparation separate flavonol compound 20.3mg.
Flavonol compound is a yellow powder, and hydrochloric acid-magnesium powder and Molish reaction all are positive.FAB
+The MS spectrum provides quasi-molecular ion peak m/z:385 ([M+H]
+), in conjunction with HR-ESI-MS (m/z:385.1294 ([M+H]
+385.1287) and the information that provides of NMR spectrum, calculated value is:, determine that its molecular formula is C
21H
20O
7, degree of unsaturation is 12.FAB
+The MS spectrum gives the fragmention of 2 features: m/z368[M+H-OH]
+There is hydroxyl, 313[M-C in the prompting molecule
4H
7O]
+There is different prenyl in the prompting molecule.
1H-NMR (table-1) (400MHz, DMSO-d
6) δ: 12.31 (1H, s), 10.57 (1H, s), 8.79 (1H s) is respectively 5,7,3 hydroxyl proton signals of flavones, 8.28 (2H, d, J=9.0Hz), 7.09 (2H, d, J=9.0Hz) there is phenyl ring AA ' BB ' spin system in prompting, and 6.34 (1H s) prompts for the proton signal that a phenyl ring five replaces.3.88 (3H s) prompts for the proton signal of a methoxyl group, and 1.82 (3H s) prompts for a methyl signals, and this methyl may be connected with two keys.
13C-NMR (table-1) (100MHz, DMSO-d
6) δ: 99～178ppm has 15 carbon signals, wherein 130.2,114.6 strength of signal be other-2 times of CH strength of signal, may be that 2 carbon signals are overlapping, this can by
1Exist AA ' BB ' spin system to be proved among the H-NMR, so should there be 17 carbon signals in this zone, remove 15 carbon signals of flavones parent nucleus, also have 2 carbon signals, wherein 110.3 are-CH
2Carbon signal illustrates there is a terminal double link that 55.7 is the carbon signal of methoxyl group, and 18.1 is the carbon signal of methyl, and 30.3 is the mesomethylene carbon signal in addition, and 75.4 is oxygen containing methine carbon signal.In the HMBC spectrum (description of drawings Fig. 1), chemical shift is at 5 hydroxyl proton signals and δ: 160.1 (C-5) of δ 12.31ppm, 99.1 (C-6), 104.0 it is relevant that carbon signal (C-10) has, hydrogen signal and the δ of δ 6.34 (H-6): 160.1 (C-5), 163.6 (C-7), 104.8 (C-8), 104.0 it is relevant that carbon signal (C-10) has, δ 8.28 (H-2 ', H-6 ') hydrogen signal and δ: 146.6 (C-2), 114.6 (C-3 ', 5 '), 161.7 it is relevant that the carbon signal of (C-4 ') has, δ 7.09 (H-3 ', 5 ') hydrogen signal and δ: 146.6 (C-2), (124.8 C-1 '), 161.7 it is relevant that the carbon signal of (C-4 ') has, and determined the signal ownership of flavones parent nucleus thus.Hydrogen signal and the δ of δ 3.02 (H-1 ＂): 163.6 (C-7), 104.8 (C-8), 155.3 (C-9), (75.4 C-2 ＂), 149.1 the carbon signal of (C-3 ＂) has relevant, hydrogen signal and the δ of δ 4.42 (H-2 ＂): 104.8 (C-8), (30.3 C-1 ＂), (149.1 C-3 ＂), (110.3 C-4 ＂), 18.1 the carbon signal of (C-5 ＂) has relevant, δ: 4.43 (Ha-4 ＂), the hydrogen signal and the δ of (4.72 Hb-4 ＂): 75.4 (C-2 ＂), (149.1 C-3 ＂), 18.1 the carbon signal of (C-5 ＂) has relevant, hydrogen signal and the δ of δ 1.82 (H-5 ＂): 75.4 (C-2 ＂), (149.1 C-3 ＂), 110.3 the carbon signal of (C-4 ＂) has relevant, can determine that thus this different isopentene group is connected on 8 of flavones parent nucleus, for: 2 ＂-hydroxyl-3 ＂-methyl-3 ＂-butenyl.It is relevant that the proton signal of δ 3.88 methoxyl groups and the carbon signal of δ 161.7 (C-4 ') have, and the prompting methoxyl group is connected 4 ' position.
In sum, the structure of flavonol compound is confirmed as: 3,5, and 7-trihydroxy--8-(2 ＂-hydroxyl-3 ＂-methyl-3 ＂-butenyl)-4 '-methoxy flavone is 2 ＂-hydroxyl-3 ＂-alkene-dehydration Icaritin, and its structural formula is as follows:
Embodiment 2
Tablet:
The flavonol compound 10mg of activeconstituents---structural formula (1)
Lactose 156mg
W-Gum 55mg
Calcium stearate 4mg
The preparation method: activeconstituents, lactose, W-Gum are mixed, and water is evenly moistening, drying, sieve after, add calcium stearate, after mixing, compacting in flakes, every heavy 225mg, active component content is 10mg.
Embodiment 3
Sprays:
The flavonol compound 8mg of activeconstituents structural formula (1)
Sodium-chlor 9mg
EDTA 0.5mg
Sodium phosphate buffer (Ph6.5) 10mg
Distilled water adds to 2ml
The preparation method: after each solids component added in the distilled water dissolving fully successively, after filtration, after the sterilization, bottling.
The anti-inflammatory action of the flavonol compound of structural formula (1) comprises following testing sequence:
1, material and method
1.1 the cell cultures cell is inoculated in 24 well culture plates after going down to posterity in containing the clear high sugared DMEM substratum of 10% tire ox.Be divided into is three groups, positive controls (LPS1mg/L handles 18h), compound 1 that blank group (no medicine and LPS handle), LPS handle (are respectively 0.5,2.5 and 12.5mg/L)+and the LPS treatment group, LPS and compound 1 are handled 18h simultaneously, and every group each three are parallel.
1.2 the toxicological evaluation of compound 1 is used the MTT detection method and is estimated.Take the logarithm vegetative period RAW cell inoculation in 96 well culture plates, 1 * 10
5Individual cells/well, 37 ℃, 5% CO
2After cultivating 20h under the condition, add 20 μ L MTT (5mg/mL) again and continue to cultivate 4h, add DMSO 150 μ L dissolving then, measure each hole light absorption value (OD value) in the 595nm place, calculate the relevant motility rate of cell with enzyme-linked immunosorbent assay instrument.
1.3 the mensuration of cytokine is got cultured cells supernatant liquor 100 μ L, according to the procedure operation of cytokine ELISA detection kit.
2, result
2.1 behind RAW264.7 monocyte-scavenger cell 20h that the toxicological evaluation 0.5,2.5 of compound 1 and the compound of 12.5mg/L concentration 1 are handled, handling positive controls with the blank group with LPS compares, the cell motility rate does not have significant difference, illustrates that 1 pair of RAW264.7 cell of compound does not have cytotoxic effect (description of drawings Fig. 2).
2.2 behind 1 pair of external LPS inductive RAW264.7 scavenger cell of the compound-blank group of monocyte TNF-α synthetic influence RAW264.7 cell cultures 18h, excretory TNF-alpha levels is respectively 1433.5 ± 417pg/mL.The secretion of TNF-α significantly increases behind LPS (1mg/L) the processing 18h, reaches 4884 ± 600pg/mL.After adding compound 1 (0.5-12.5mg/L) and LPS co-processing, there is concentration dependent (description of drawings Fig. 3) in RAW264.7 excretory TNF-α.Compare with the positive controls that LPS handles, 0.5 and the compound 1 of 12.5mg/L concentration can suppress TNF-α significantly, inhibiting rate is respectively 17.1% (p＜0.01), 55.6% (p＜0.01), 2.5mg/L the compound 1 of concentration can suppress TNF-α, but difference not significantly (p〉0.05) inhibiting rate be 20.1%.
2.3 the IL-10 that 1 pair of external LPS inductive RAW264.7 cell IL-10 synthetic of compound influences the RAW264.7 emiocytosis of blank group is respectively 19.435 ± 2.32pg/mL, significantly is lower than positive controls 100.64 ± 6.15pg/mL (description of drawings Fig. 4) that LPS handles.For the RAW cell, the IL-10 0.5-12.5mg/L the compound 1 of concentration can raise, the IL-10 level 0.5mg/L the compound 1 of concentration can raise, the compound 1 of the promotion rate is 8% (p〉0.05) .2.5 and the 12.5mg/L concentration IL-10 level that can significantly raise, be respectively 115.11 ± 14.16pg/mL and 127.6 ± 8.39pg/mL, the promotion rate is 15% and 27% (p＜0.01).
Table-1 compound 1
1H-NMR and
13C-NMR data (δ: ppm; J:Hz)
Annotate: compound 1
1H-NMR and
13C-NMR measures in 400MHz and 100MHz respectively; Solvent is: DMSO
Claims (4)
1. flavonol compound has following structural formula:
2. the preparation method of flavonol compound according to claim 1 is characterized in that comprising the following steps:
A, dry Herba Epimedii herb pulverized after, press Herba Epimedii: the mass/volume ratio of aqueous acetone solution=1:2～4, it is 75% aqueous acetone solution that Herba Epimedii is put into concentration, after soaking 15～30 hours under the room temperature, get extracting solution, so repeat to extract united extraction liquid 2～3 times;
B, with the underpressure distillation of above-mentioned A step gained extracting solution after do not have acetone flavor, press extracting solution: the volume ratio of sherwood oil=1: 1, under room temperature, extracting solution is carried out 2～3 times extraction with sherwood oil, reclaim sherwood oil after, must extraction liquid;
C, press extraction liquid: the volume ratio of ethyl acetate=1: 1, under room temperature, the extraction liquid of above-mentioned B step is carried out 2～3 times extraction with ethyl acetate, after the recovery ethyl acetate medicinal extract;
D, silicagel column on the ethyl acetate medicinal extract of above-mentioned C step is carried out chromatographic separation, use chloroform: methyl alcohol=40～0: the mixture of 1 volume ratio carries out wash-out as eluent, remove impurity after, the roughing out thing;
E, the roughing out thing of above-mentioned D step is carried out the silica gel column chromatography identical with step D and wash-out 2～5 times, remove impurity after, smart isolate;
F, the smart isolate of E step gained analyzed with the efficient liquid phase chromatographic analysis instrument after, after separating with half preparation of ZORBAX SB-C18 post flavonol compound.
3, be used for antiphlogistic pharmaceutical composition, wherein contain compound and the pharmaceutically acceptable carrier or the auxiliary material of the claim 1 for the treatment of significant quantity.
4, the application of claim 1 compound in the preparation anti-inflammatory drug.
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| CN109393254A (en) * | 2017-08-18 | 2019-03-01 | 彦臣生技药品股份有限公司 | Composition and method for improving insect immunity |
| CN111995628A (en) * | 2020-07-17 | 2020-11-27 | 山东省中医药研究院 | Novel compound extracted from coptis chinensis medicinal material and extraction separation method and application thereof |
| CN113072526A (en) * | 2021-03-30 | 2021-07-06 | 滨州医学院 | Anthraquinone/coumarin dimer novel skeleton compound and preparation method and application thereof |
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| CN101205223B (en) * | 2006-12-18 | 2010-10-06 | 李毅林 | Total synthesis method of natural product barrenwort glycosides compounds |
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| CN109393254A (en) * | 2017-08-18 | 2019-03-01 | 彦臣生技药品股份有限公司 | Composition and method for improving insect immunity |
| CN111995628A (en) * | 2020-07-17 | 2020-11-27 | 山东省中医药研究院 | Novel compound extracted from coptis chinensis medicinal material and extraction separation method and application thereof |
| CN111995628B (en) * | 2020-07-17 | 2023-02-03 | 山东省中医药研究院 | Novel compound extracted from coptis chinensis medicinal material and extraction separation method and application thereof |
| CN113072526A (en) * | 2021-03-30 | 2021-07-06 | 滨州医学院 | Anthraquinone/coumarin dimer novel skeleton compound and preparation method and application thereof |
| CN113072526B (en) * | 2021-03-30 | 2022-09-13 | 滨州医学院 | Anthraquinone/coumarin dimer compound and preparation method and application thereof |
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