CN101200743B - Method for preparing hydrated icaritin - Google Patents
Method for preparing hydrated icaritin Download PDFInfo
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- CN101200743B CN101200743B CN2007101796738A CN200710179673A CN101200743B CN 101200743 B CN101200743 B CN 101200743B CN 2007101796738 A CN2007101796738 A CN 2007101796738A CN 200710179673 A CN200710179673 A CN 200710179673A CN 101200743 B CN101200743 B CN 101200743B
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- TUUXBSASAQJECY-UHFFFAOYSA-N 3,5,7-trihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)chromen-4-one Chemical compound C1=CC(OC)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C(CC=C(C)C)=C2O1 TUUXBSASAQJECY-UHFFFAOYSA-N 0.000 title claims description 74
- CTGVBHDTGZUEJZ-UHFFFAOYSA-N Noricaritin Natural products CC(C)(O)CCC1=C(O)C=C(O)C(C(C=2O)=O)=C1OC=2C1=CC=C(O)C=C1 CTGVBHDTGZUEJZ-UHFFFAOYSA-N 0.000 title claims description 37
- 238000000034 method Methods 0.000 title description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 73
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
- TZJALUIVHRYQQB-UHFFFAOYSA-N icariine Natural products C1=CC(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(C)O2)O)C(=O)C2=C(O)C=C(OC3C(C(O)C(O)C(CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 25
- 238000002360 preparation method Methods 0.000 claims abstract description 22
- 230000007062 hydrolysis Effects 0.000 claims abstract description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- 108010059892 Cellulase Proteins 0.000 claims description 20
- 229940106157 cellulase Drugs 0.000 claims description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 239000011347 resin Substances 0.000 claims description 12
- 229920005989 resin Polymers 0.000 claims description 12
- 239000007795 chemical reaction product Substances 0.000 claims description 10
- 238000013016 damping Methods 0.000 claims description 7
- 239000012530 fluid Substances 0.000 claims description 7
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 239000012535 impurity Substances 0.000 claims description 6
- 108090000790 Enzymes Proteins 0.000 claims description 5
- 102000004190 Enzymes Human genes 0.000 claims description 5
- 239000003463 adsorbent Substances 0.000 claims description 5
- 229940088598 enzyme Drugs 0.000 claims description 5
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 238000002425 crystallisation Methods 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- 229940045641 monobasic sodium phosphate Drugs 0.000 claims description 4
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 4
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 4
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 4
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 4
- 239000001488 sodium phosphate Substances 0.000 claims description 4
- 235000011008 sodium phosphates Nutrition 0.000 claims description 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 4
- 239000000376 reactant Substances 0.000 claims description 3
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 2
- 239000000835 fiber Substances 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000001179 sorption measurement Methods 0.000 claims 1
- 235000018905 epimedium Nutrition 0.000 abstract description 8
- 239000000126 substance Substances 0.000 abstract description 8
- 229930014626 natural product Natural products 0.000 abstract description 2
- TZJALUIVHRYQQB-XFDQAQKOSA-N Icariin Natural products O(C)c1ccc(C2=C(O[C@H]3[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O3)C(=O)c3c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O4)c(C/C=C(\C)/C)c3O2)cc1 TZJALUIVHRYQQB-XFDQAQKOSA-N 0.000 abstract 5
- TZJALUIVHRYQQB-XLRXWWTNSA-N icariin Chemical compound C1=CC(OC)=CC=C1C1=C(O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)C(=O)C2=C(O)C=C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-XLRXWWTNSA-N 0.000 abstract 5
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 abstract 2
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 abstract 2
- 241001016310 Epimedium grandiflorum Species 0.000 abstract 2
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 abstract 2
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 229920002678 cellulose Polymers 0.000 abstract 1
- 239000001913 cellulose Substances 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 7
- 241000893536 Epimedium Species 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
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- 238000003756 stirring Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
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- 239000012043 crude product Substances 0.000 description 2
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- 238000003810 ethyl acetate extraction Methods 0.000 description 2
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- 239000007791 liquid phase Substances 0.000 description 2
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- 206010006458 Bronchitis chronic Diseases 0.000 description 1
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- 241001660849 Epimedium pubescens Species 0.000 description 1
- 241001362411 Epimedium sagittatum Species 0.000 description 1
- 241001362415 Epimedium wushanense Species 0.000 description 1
- 208000007443 Neurasthenia Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
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- 238000010438 heat treatment Methods 0.000 description 1
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- 238000004128 high performance liquid chromatography Methods 0.000 description 1
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- 239000004615 ingredient Substances 0.000 description 1
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- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention relates to a preparation method of hydrated icariin which belongs to the synthesis field of natural compounds. The preparation method of the hydrated icariin is characterized in that the hydrated icariin is obtained from icariin after two steps of the hydrolysis reaction of hydrochloride and cellulose. The desugarization hydrolysis is complete. The chemical structure of barrenwort aglycone can be changed, which changes the barrenwort aglycone into the hydrated icariin. The yield is high. The treatment after the reaction is convenient. And the purity of products fully complies with the medical standards.
Description
Technical field
The present invention relates to the synthetic of natural compounds, particularly relate to the preparation method of the composition hydrated icaritin in a kind of Chinese medicine Herba Epimedii.
Background technology
Herba Epimedii is the Chinese medicinal materials of using always, it is the ground drying nest of Berberidaceae (Berberridaceae) Epimedium (Epimedium genus) various plants, Pharmacopoeia of People's Republic of China (2000 editions) has been included following five kinds of epimedium herbs, i.e. Herba Epimedii (Epimedium brevicomum Maxim)), arrow leaf Herba Epimedii (Epimedium sagittatum), pubescence Herba Epimedii (Epimedium pubescens), Epimedium wushanense (Epimedium wushanenes), Herba Epimedii (Epimedium koreanum Nakai) etc.The effect that Herba Epimedii has kidney invigorating and YANG supporting, strengthening the muscles and bones, dispels rheumatism is usually used in treating that impotence erectile problem, urine are dripping, weakness of the waist and knees and diseases such as coronary heart disease, chronic bronchitis, neurasthenia and poliomyelitis.Modern pharmacological research proves that Herba Epimedii contains special chemical ingredients and significant biological activity.
Hydrated icaritin, chemical name: 3,5,7-trihydroxy--4 '-methoxyl group-8-(3-methyl-3-hydroxyl)-butyl-flavones.Shown in the chemical structure (I).
Natural hydrated icaritin has two kinds of sources, and a kind of is the free hydrated icaritin, has report to separate from Herba Epimedii in early days and obtains; Another kind is to derive from and sugared bonded glucoside, can get through hydrolysis.But because of its content in plant is very low, thus can't carry out preparation of industrialization (Chemical and pharmacological investigations of Epimediumspecies:a survey,
Prog.Drug Res.2003; 60,1-57.The research new development of Herba Epimedii, Chinese Pharmaceutical Journal, 1997,32,449-451).
Summary of the invention
Icarin, chemical name is: 3,5,7-trihydroxy--4 ' methoxyl group-8-isoamylene radical chromocor-3-O-α-L-pyrans rhamnosyl-7-O-β-D-glucopyranoside.Its structural formula is shown in (II)
Abundant because of naturally occurring icarin content in plant, a kind ofly prepare the method for hydrated icaritin so the invention provides from icarin, reaction yield is higher, whole simple operation of process, post-reaction treatment makes things convenient for, and purifying is simple.
A kind of preparation method of hydrated icaritin is characterized in that: comprise by icarin obtaining through hydrochloric acid and the reaction of cellulase two one-step hydrolysis.
The said hydrolyzed reactions steps is the plain enzymic hydrolysis of icarin reprocess fibre behind hydrochloric acid hydrolysis.
In the described hydrochloric acid hydrolysis reaction, concentration of hydrochloric acid is 1N-5N, and reactant ratio is every 1g icarin and the reaction of 20-100mL hydrochloric acid solution, and temperature of reaction is 50-100 ℃, and the reaction times is 0.5-2 hour.
The preferably salt acid concentration is 3N, and ratio is every 1g icarin and the reaction of 50mL hydrochloric acid solution, and temperature of reaction is 80 ℃, and be 1 hour heat-up time.
In the described cellulase hydrolysis reaction, reaction conditions is 40-50 ℃, pH be in SODIUM PHOSPHATE, MONOBASIC-Sodium phosphate dibasic damping fluid of 4.8-5.5 with above-mentioned hydrochloric acid reaction product with cellulase hydrolysis 24-36 hour, the comprehensive enzyme activity of described cellulase 〉=1.8 ten thousand u/mL.
Preferred reaction conditions is 40 ℃, pH be in SODIUM PHOSPHATE, MONOBASIC-Sodium phosphate dibasic damping fluid of 5.0 with above-mentioned hydrochloric acid reaction product with cellulase hydrolysis 36 hours.
A kind of preparation method of hydrated icaritin comprises also that the purifying of hydrated icaritin, described purifying comprise with solvent to extract, adopt macroporous adsorbent resin to remove impurity and three steps of methanol-water solution weight crystallization from hydrolysis reaction mixture.
Described solvent is an ethyl acetate.
The suction of hydrated icaritin is taken off and is adopted 50%, 60%, 70% ethanol-water solution wash-out successively on the described macroporous adsorbent resin.
Described methanol-water solution contains methyl alcohol 95-98% (V/V).
From the icarin to the hydrated icaritin, key is not only will be with the 3-of icarin, and the sugared substituting group hydrolysis on the 7-is fallen, and will be on the 8-of icarin isopentene group adduction a part water, make it generate hydrated icaritin.The contriver has done long term studies and exploration, finds that cellulase can hydrolysis 7-glucose substituting group, but a spot of 3-rhamnosyl of hydrolysis substituting group only.Hydrochloric acid soln energy complete hydrolysis 3-rhamnosyl substituting group, but partial hydrolysis 7-glucose substituting group, the hydrolysis reaction of hydrochloric acid can form addition reaction with a part water on two keys simultaneously.In the hydrochloric acid soln of different concns, under the different temperature of reaction, and in different hydrochloric acid and the cellulase hydrolysis order, the yield of the hydrated icaritin of its generation is different.The preferred the first step of the present invention is reacted with 3N hydrochloric acid and icarin, and second step was used cellulase hydrolysis, can obtain the hydrated icaritin yield higher than other additive methods of having attempted.
The purifying of the hydrated icaritin of the present invention's preparation directly extracts hydrated icaritin with ethyl acetate from reaction solution behind enzyme digestion reaction.Ethyl acetate layer can be removed insoluble impurity after filtration, as the purifying first time, and can be used for next step purification process.
Going on foot purification step down comprises: the above-mentioned ethyl acetate layer that contains reaction product is mixed sample with macroporous adsorbent resin, reclaim ethyl acetate, reaction product is adsorbed on the resin, the resin of mixing behind the sample is added on the macroporous adsorptive resins, with 50%, 60%, 70% ethanolic soln is wash-out successively, collection contains the cut of hydrated icaritin, concentrates to reclaim ethanol to small volume, promptly has the hydrated icaritin precipitation to separate out.The hydrated icaritin of separating out filters with the dissolving of 95-98% methyl alcohol repeated multiple times, concentrates, and separates out, and can obtain the purity more than 99%, and make hydrated icaritin be needle crystal.
The present invention adopts hydrochloric acid and cellulase that the hydration icarin is reacted, and its desaccharification hydrolysis is complete, and can change the chemical structure of epimedium aglucone, make it become hydrated icaritin, and yield is higher.Post-reaction treatment is convenient, and product purity meets medicinal standard fully.
Description of drawings
The hydrated icaritin HPLC collection of illustrative plates that Fig. 1 embodiment 1 makes
The hydrated icaritin X scatter pattern that Fig. 2 embodiment 1 makes
Embodiment
The present invention is described in further detail below in conjunction with embodiment.
Embodiment 1
1.1 the reaction of icarin and hydrochloric acid soln:
Get icarin 5g (content is more than 90%), be added in the hydrochloric acid soln of 250mL 3N (concentrated hydrochloric acid and water by 3: 7 volume ratio preparation), stir, progressively be warming up to 80 ℃, and kept 1 hour.After reaction finished, cooling was placed, and made precipitation fully.Filter, throw out washes with water for several times to neutral (as can't be washed till neutrality, in the available small amount of N aOH solution and acid).Filtrate discards or is left to down secondary response and uses.
1.2 the reaction of hydrochloric acid reaction product and cellulase
Above-mentioned hydrochloric acid reaction product is added to 250mLNaH
2PO
4-Na
2HPO
4(pH5.0 in damping fluid 50uM), adds the about 5mL of cellulase (comprehensive enzyme activity 〉=1.8 ten thousand u/mL) again, stirs 36 hours in 40 ℃.After reaction finished, cooling added equivalent ethyl acetate extraction twice, and the combined ethyl acetate layer filters, and removes insoluble impurities.
1.3 the aftertreatment of reaction solution:
Add about 50g DM130 resin in the above-mentioned ethyl acetate solution and mix sample, reclaim ethyl acetate to doing.The resin of mixing behind the sample is added on the 200g macroporous adsorptive resins, and with 50%, 60%, 70% ethanolic soln is wash-out successively, collects the cut that contains hydrated icaritin, concentrates to reclaim ethanol to small volume, and existing hydrated icaritin precipitation is separated out.Filter, get the about 2g of hydrated icaritin crude product, yield is about 40%.
1.4 the pure product preparation of hydrated icaritin:
The hydrated icaritin crude product of collecting with 95-98% methyl alcohol 600mL heating for dissolving, removes by filter impurity, is concentrated into about 150mL, has crystallization to separate out.Monitor purity so repeatedly with about 6-10 time of methanol crystallization, and with high performance liquid phase, until reaching medicinal standard.Can get the about 1.5g of the pure product of hydrated icaritin.High performance liquid phase moving phase is acetonitrile and 0.3% phosphate aqueous solution, and ratio is 52: 48, and chromatographic column is C18,200 * 4.6mm, 5um.The hydrated icaritin retention time is about 18min.See Fig. 1.
1.5 structural identification and physical and chemical parameter:
1.5.1 hydrated icaritin, the methanol-water recrystallization gets yellow needle-like crystal, and fusing point is 238-9 ℃.
1.5.2 NMR data
NMR instrument: Brucker AM-400 NMR Spectrometer.
Solvent: DMSO
Test event:
1H,
13C, DEPT-135.
Survey formula result::
1H-NMR:1.18 (6H, s); 1.55 (2H, m); 2.50 (2H, m); 3.85 (3H, s); 4.31 (1H, s); 6.28 (1H, s); 7.09 (2H, d, J=9Hz); 8.23 (2H, d, J=9Hz); 9.50 (1H, s); 10.61 (1H, s); 12.33 (1H, s).
13C-NMR：18.09；29.81；43.58；56.03；69.53；98.46；103.72；107.52；114.64；124.31；129.94；136.55；146.62；154.13；158.75；161.13；162.02；176.95。
1.5.3 Mass data
MS instrument: Agilent LC/MS Apparatus.
Condition determination: ESI Source.
Measurement result: (M+H)
+M/z 387.2.
1.5.4 the X scatter pattern is seen Fig. 2.
2.1 the reaction of icarin and cellulase
Get icarin 5g (content is more than 90%), add to 250mLNaH
2PO
4-Na
2HPO
4(pH4.8 in damping fluid 50uM), adds the about 5mL of cellulase (comprehensive enzyme activity 〉=1.8 ten thousand u/mL) again, stirs 24 hours in 50 ℃.After reaction finished, cooling was placed, and made precipitation fully.Filter, throw out washes with water for several times.
2.2 the reaction of enzymolysis product and hydrochloric acid soln:
Above-mentioned enzymolysis product is added in the hydrochloric acid soln of 500mL 1N (concentrated hydrochloric acid and water by 1: 10 volume ratio preparation), stirs, progressively be warming up to 60 ℃, and kept 8 hours.After reaction finished, cooling was placed, and made precipitation fully, filtered.Throw out washes with water to neutrality.
2.3 the aftertreatment of reaction solution: (with embodiment 1), yield is about 10%.
2.4 the pure product preparation of hydrated icaritin: (with embodiment 1)
Embodiment 3
3.1 the reaction of icarin and hydrochloric acid soln:
Get icarin 5g (content is more than 90%), be added in the hydrochloric acid soln of 500mL 1N (concentrated hydrochloric acid and water by 1: 10 volume ratio preparation), stir, progressively be warming up to 80 ℃, and kept 8 hours.After reaction finished, cooling was placed, and made precipitation fully.Filter, throw out washes with water for several times to neutral (as can't be washed till neutrality, in the available small amount of N aOH solution and acid).Filtrate discards or is left to down secondary response and uses.
3.2 the reaction of hydrochloric acid reaction product and cellulase
Above-mentioned hydrochloric acid reaction product is added to 250mLNaH
2PO
4-Na
2HPO
4(pH5.5 in damping fluid 50uM), adds the about 5mL of cellulase (comprehensive enzyme activity 〉=1.8 ten thousand u/mL) again, stirs 32 hours in 40 ℃.After reaction finished, cooling added equivalent ethyl acetate extraction twice, and the combined ethyl acetate layer filters, and removes insoluble impurities.
3.3 the aftertreatment of reaction solution: (with embodiment 1), yield is about 20%.
3.4 the pure product preparation of hydrated icaritin: (with embodiment 1).
Claims (8)
1. the preparation method of a hydrated icaritin, it is characterized in that: comprise by icarin obtaining through hydrochloric acid and the reaction of cellulase two one-step hydrolysis, in the described hydrochloric acid hydrolysis reaction, concentration of hydrochloric acid is 3N-5N, reactant ratio is every 1g icarin and the reaction of 20-100mL hydrochloric acid solution, temperature of reaction is 50-100 ℃, and the reaction times is 0.5-2 hour; In the described cellulase hydrolysis reaction, reaction conditions is 40-50 ℃, pH be in SODIUM PHOSPHATE, MONOBASIC-Sodium phosphate dibasic damping fluid of 4.8-5.5 with the hydrochloric acid hydrolysis reaction product with cellulase hydrolysis 24-36 hour, the comprehensive enzyme activity of described cellulase 〉=1.8 ten thousand u/mL.
2. preparation method according to claim 1, the order of described hydrolysis reaction step are the plain enzymic hydrolysiss of icarin reprocess fibre behind hydrochloric acid hydrolysis.
3. preparation method according to claim 1, described concentration of hydrochloric acid is 3N, and reactant ratio is every 1g icarin and the reaction of 50mL hydrochloric acid solution, and temperature of reaction is 80 ℃, and be 1 hour heat-up time.
4. preparation method according to claim 1, described reaction conditions is 40 ℃, pH be in SODIUM PHOSPHATE, MONOBASIC-Sodium phosphate dibasic damping fluid of 5.0 with the hydrochloric acid hydrolysis reaction product with cellulase hydrolysis 36 hours.
5. preparation method according to claim 1 comprises also that the purifying of hydrated icaritin, described purifying comprise with solvent to extract, adopt macroporous adsorbent resin to remove impurity and three steps of methanol-water solution weight crystallization from hydrolysis reaction mixture.
6. preparation method according to claim 5, described solvent is an ethyl acetate.
7. preparation method according to claim 5, described macroporous adsorbent resin is a nonpolar macroporous adsorption resin, the wash-out of hydrated icaritin adopts 50%, 60%, 70% ethanol-water solution wash-out successively.
8. preparation method according to claim 5, described methanol-water solution contains methyl alcohol 95-98% (V/V).
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| CN101200743B true CN101200743B (en) | 2010-12-15 |
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| CN102093450B (en) * | 2010-12-24 | 2013-09-04 | 台州市黄岩源宏医化科技有限公司 | Method for synthesizing icariin by glucosidation of dehydrated epimedium herb |
| CN103305564B (en) * | 2013-07-05 | 2014-10-15 | 西安瑞天生物科技有限公司 | Method for converting icariin to herba epimedii |
| CN104230870A (en) * | 2014-09-16 | 2014-12-24 | 北京盛诺基医药科技有限公司 | Icaritin compound and application thereof |
| CN110699263B (en) * | 2019-10-29 | 2021-05-11 | 浙江工业大学 | Aspergillus niger YH-6 and application thereof in improving content of icaritin in epimedium |
| CN114671840B (en) * | 2021-12-30 | 2023-03-28 | 西安岳达生物科技股份有限公司 | Preparation method of icariin derivative |
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