CN104109178A - Preparation method of hydroxysafflor yellow A - Google Patents
Preparation method of hydroxysafflor yellow A Download PDFInfo
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- CN104109178A CN104109178A CN201410355732.2A CN201410355732A CN104109178A CN 104109178 A CN104109178 A CN 104109178A CN 201410355732 A CN201410355732 A CN 201410355732A CN 104109178 A CN104109178 A CN 104109178A
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Abstract
The invention belongs to the field of medicines, relates to a purification preparation method of a traditional Chinese medicine red flower medicinal component, and specifically relates to a preparation method of hydroxysafflor yellow A. A purifying method of the hydroxysafflor yellow A adopts macroporous adsorption resin for purifying, and adopts water or low-concentration alcohol for eluting, so that the purity of the finally obtained hydroxysafflor yellow A exceeds 99%, and yield of the hydroxysafflor yellow A exceeds 80%. The preparation method disclosed by the invention is simple to operate, low in cost, high in product purity, high in yield and suitable for large-scale industrial production preparation of the hydroxysafflor yellow A.
Description
Technical field
The invention belongs to field of medicaments, relate to a kind of purification preparation technology of Chinese medicine safflower medicinal ingredients, specifically relate to a kind of preparation method of hydroxyl radical carthamin yellow carthamus A.
Background technology
Chinese medicine safflower derives from the dried floral of feverfew Carthamus tinctorious L., and property is pungent, warm, has the effect of promoting blood circulation to restore menstrual flow blood stasis removing analgesic.Modern pharmacology research shows, the main active component of safflower concentrates on water miscible carthamin yellow.Carthamin yellow is flavonoid compound, has the effects such as coronary artery dilator, anti-oxidant, anti-inflammatory, and itself or a kind of platelet activation factor inhibitor, can suppress the formation of thrombus, for the treatment of cardiovascular and cerebrovascular diseases simultaneously.Further research shows, carthamin yellow is the mixture of three kinds of water soluble components: hydroxyl radical carthamin yellow carthamus A, carthamin yellow carthamus B Flos Carthami yellow pigment C, wherein the content of hydroxyl radical carthamin yellow carthamus A (hydroxysafflor yellow-A) is the highest, safflower Quality Element for pharmacopeia regulation, be the most effective water soluble component of safflower pharmacological effect, its structural formula is as follows:
In view of carthamin yellow compounds structural similitude, and all have very strong water-soluble, the preparation technology of hydroxyl radical carthamin yellow carthamus A sterling is comparatively loaded down with trivial details and cost is higher, and domestic research never obtains satisfied achievement, ubiquity extraction process length consuming time, the problem such as energy consumption is high, yield is low.Chinese patent (publication number: CN101195647A) adopt macroporous adsorbent resin to carry out after preliminary purification hydroxyl radical carthamin yellow carthamus A crude product, re-using gel resin is further purified, the sample purity obtaining can reach more than 99%, yet, the dextrane gel resin price of using in this technique is expensive, and its yield only reaches 50%, long processing period and numerous and diverse simultaneously, application difficulty is large, is difficult for being applied in large-scale industrial production.Chinese patent (publication number: CN102127124A) adopt high speed adverse current chromatogram Refine HSYA, the sample purity obtaining can reach 97%.Yet high-speed counter-current chromatograph device price is high, and a small amount of sample can only be prepared at every turn, the in enormous quantities demand of drug development to product cannot be met.
For these reasons, the inventor has developed the preparation method of hydroxyl radical carthamin yellow carthamus A in long-term research and practice, and the product purity that the method obtains is high, simple to operate, can meet drug development, the demand that particularly meets injection formulations bulk drug, DEVELOPMENT PROSPECT is wide.
Summary of the invention
For overcoming above problem, the invention provides a kind of technique reasonable, simple to operate, yield is high, and production cost is low, is suitable for the hydroxyl radical carthamin yellow carthamus A preparation method of suitability for industrialized production.
A hydroxyl radical carthamin yellow carthamus A preparation method, comprises the steps:
1) take the solution of Flos Carthami extract or hydroxyl radical carthamin yellow carthamus A crude product is raw material, regulates pH value to 6～9 as sample solution;
2) sample solution is added to macroporous adsorptive resins, using water or lower concentration alcohol as elutriant wash-out, collect effluent liquid;
3) concentrate drying.
Preferably, step 1) the pH value regulate process in, by adding sodium hydroxide solution to regulate pH value.Add the amount of sodium hydroxide solution to determine according to raw material, preferably the concentration of sodium hydroxide solution is 2M.
The pH value of the raw material preferably, step 1) is adjusted to 7～9, and more preferably 9.
Preferably, the sample solution step 2) is 1～2:1 with weight resin ratio.
Preferably, the macroporous adsorptive resins aspect ratio step 2) is 5～10:1.
Preferably, step 2) the loading flow velocity described in is 1～5bV/h, and more preferably 2～3bV/h, most preferably is 2～2.5bV/h.
Preferably, the elutriant step 2) is deionized water or distilled water.
Preferably, step 2) methyl alcohol or ethanol that the elutriant described in is lower concentration, more preferably 0～15% methyl alcohol or 0～10% ethanol.
Preferably, the elutriant elution flow rate step 2) is 1～5bV/h, more preferably 2～3bV/h.
Preferred, specifically comprise the steps:
1) get flos carthami, add 10% ethanol, 40 ℃ of supersound extraction twice, each 1h, extracting liquid filtering, merging filtrate, concentrated, with 2M sodium hydroxide, regulate concentrated solution to pH=9;
2) with sample solution and weight resin, than macroporous adsorptive resins in the ratio of 1:1, adsorb, macroporous adsorptive resins aspect ratio 10:1, loading flow velocity is 2bV/h, after loading absorption, adopt deionized water wash-out, elution flow rate is 2bV/h, collects effluent liquid, HPLC detects effluent liquid, merges purity and surpasses 99% effluent liquid;
3) concentrated, the lyophilize (or spraying is dry) of low-voltage vacuum, finally obtains highly purified hydroxyl radical carthamin yellow carthamus A powder.
Hydroxyl radical carthamin yellow carthamus A crude product derives from commercially available or prepares according to extracting method of the prior art, Flos Carthami extract can obtain with reference to following methods: take dry saffron powder, 20% ethanol that adds 10 times of amounts, maintaining and extracting temperature is 40 degrees Celsius, supersound extraction 1 hour, filters collection filtrate and obtains Flos Carthami extract.
The present inventor surprisingly finds, when pH regulator to 6～9 of sample solution, efficiently solve the drawback that in background technology, prior art exists, final in the situation that not reducing productive rate, still the purity that obtains hydroxyl radical carthamin yellow carthamus A surpasses 99%, after the present invention is optimized other purification conditions, yield can surpass 80%.
Accompanying drawing explanation
Fig. 1 is the high performance liquid phase collection of illustrative plates of the hydroxyl radical carthamin yellow carthamus A powder that obtains of embodiment 1.
Embodiment
Below in conjunction with specific embodiment, further set forth the present invention, should be understood that following examples are only not used in and limit the scope of the invention for the present invention is described.
In the following example, method therefor if no special instructions, is ordinary method.Needed material or reagent in following examples, be if no special instructions market and buy.
Embodiment 1:
Get flos carthami 100g (hydroxyl radical carthamin yellow carthamus A content 1.7%); add 10% ethanol 1L; twice of 40 ℃ of supersound extraction; each 1h; extracting liquid filtering; merging filtrate; be concentrated into 1L; adopt 2M sodium hydrate regulator solution to pH=9; with sample solution and weight resin, than macroporous adsorptive resins in the ratio of 1:1, adsorb (macroporous adsorptive resins specification and model: 1000mL, No. 1, microballoon, Shanghai Huazhen Science and Technology Co., Ltd.); macroporous adsorptive resins aspect ratio 10:1, loading flow velocity 2bV/h.After loading absorption, adopt deionized water as elutriant wash-out, elution flow rate 2bV/h, collect effluent liquid, HPLC detects effluent liquid, merge purity and surpass 99% effluent liquid, low-voltage vacuum is concentrated, lyophilize, finally obtains 99.3% hydroxyl radical carthamin yellow carthamus A powder 1.51g (yield 88.8%).
HPLC detection method: select C18 chromatographic column, Agilent HP1260 liquid chromatograph, mobile phase methanol: acetonitrile: 0.7% phosphoric acid=26:2:72, detects wavelength 403nm, sampling volume 10 μ L.
Embodiment 2:
Purifying is adjusted to 8:1 with macroporous adsorptive resins aspect ratio, and all the other finally obtain 99.3% hydroxyl radical carthamin yellow carthamus A 1.48g with embodiment 1.(yield 87.1%)
Embodiment 3:
Purifying is adjusted to 5:1 with macroporous adsorptive resins aspect ratio, and all the other finally obtain 99.2% hydroxyl radical carthamin yellow carthamus A 1.40g with embodiment 1.(yield 82.4%)
Comparative example 1:
Purifying is adjusted to 4:1 with macroporous adsorptive resins aspect ratio, and all the other finally obtain 99.0% hydroxyl radical carthamin yellow carthamus A 1.28g with embodiment 1.(yield 75.3%)
Comparative example 2:
Purifying is adjusted to 15:1 with macroporous adsorptive resins aspect ratio, and all the other finally obtain 99.0% hydroxyl radical carthamin yellow carthamus A 1.39g with embodiment 1.(yield 81.8%)
Embodiment 4:
Purifying is adjusted to 5:1 with macroporous adsorptive resins aspect ratio, and last drying step adopts spray-drying process, and all the other finally obtain 99.2% hydroxyl radical carthamin yellow carthamus A 1.36g with embodiment 1.(yield 80.0%)
Embodiment 5:
Drying step adopts spray-drying process, and all the other finally obtain 99.2% hydroxyl radical carthamin yellow carthamus A 1.42g with embodiment 1.(yield 83.5%)
Embodiment 6:
Purifying adopts the XAD-2 resin of ROHM AND HAAS resin company limited production with the resin of macroporous adsorptive resins, all the other finally obtain the hydroxyl radical carthamin yellow carthamus A 1.41g of purity 99.0% with embodiment 1.(yield 82.9%)
Embodiment 7:
Purifying adopts the YPR-2 resin of Anhui Samsung resin company limited production with the resin of macroporous adsorptive resins, all the other finally obtain the hydroxyl radical carthamin yellow carthamus A 1.37g of purity 99.1% with embodiment 1.(yield 80.6%)
Embodiment 8:
During purifying, regulate safflower to extract concentrated solution to pH=6, all the other finally obtain the hydroxyl radical carthamin yellow carthamus A 1.39g of purity 99.1% with embodiment 1.(yield 81.8%)
Embodiment 9:
During purifying, regulate safflower to extract concentrated solution to pH=8, all the other finally obtain the hydroxyl radical carthamin yellow carthamus A 1.44g of purity 99.2% with embodiment 1.(yield 84.7%)
Comparative example 3:
During purifying, regulate safflower to extract concentrated solution to pH=5, all the other finally obtain 99.1% hydroxyl radical carthamin yellow carthamus A 1.22g with embodiment 1.(yield 71.8%)
Comparative example 4:
During purifying, regulate safflower to extract concentrated solution to pH=10, all the other finally obtain 99.2% hydroxyl radical carthamin yellow carthamus A 0.86g with embodiment 1.(yield 50.6%)
Embodiment 10:
During purifying, sample solution is with weight resin than being 2:1, and all the other finally obtain the hydroxyl radical carthamin yellow carthamus A 1.53g of purity 99.2% with embodiment 1.(yield 90%)
Comparative example 5:
During purifying, sample solution is with weight resin than being 0.5:1, and all the other finally obtain the hydroxyl radical carthamin yellow carthamus A 1.29g of purity 99.0% with embodiment 1.(yield 75.9%)
Comparative example 6:
During purifying, sample solution is with weight resin than being 2.5:1, and all the other finally obtain the hydroxyl radical carthamin yellow carthamus A 1.16g of purity 99.0% with embodiment 1.(yield 68.2%)
Embodiment 11:
Elutriant adopts 10% methyl alcohol, and all the other finally obtain the hydroxyl radical carthamin yellow carthamus A 1.39g of purity 99.2% with embodiment 1.(yield 81.8%)
Embodiment 12:
Elutriant adopts 15% methyl alcohol, and all the other finally obtain the hydroxyl radical carthamin yellow carthamus A 1.41g of purity 99.3% with embodiment 1.(yield 82.9%)
Comparative example 7:
Elutriant adopts 20% methyl alcohol, and all the other finally obtain the hydroxyl radical carthamin yellow carthamus A 1.30g of purity 99.0% with embodiment 1.(yield 76.5%)
Embodiment 13:
Elutriant adopts 5% ethanol, and all the other finally obtain the hydroxyl radical carthamin yellow carthamus A 1.39g of purity 99.2% with embodiment 1.(yield 81.8%)
Embodiment 14:
Elutriant adopts 10% ethanol, and all the other finally obtain the hydroxyl radical carthamin yellow carthamus A 1.40g of purity 99.3% with embodiment 1.(yield 82.4%)
Comparative example 8:
Elutriant adopts 15% ethanol, and all the other finally obtain 99.0% hydroxyl radical carthamin yellow carthamus A 1.28g with embodiment 1.(yield 75.0%)
Embodiment 15:
Loading flow velocity changes 5bV/h into, and all the other finally obtain 99.2% hydroxyl radical carthamin yellow carthamus A 1.43g with embodiment 1.(yield 84.1%)
Embodiment 16:
Loading flow velocity changes 1bV/h into, and all the other finally obtain 99.2% hydroxyl radical carthamin yellow carthamus A 1.44g with embodiment 1.(yield 84.7%)
Comparative example 9:
Loading flow velocity changes 6bV/h into, and all the other finally obtain 99.1% hydroxyl radical carthamin yellow carthamus A 1.28g with embodiment 1.(yield 75.3%)
Embodiment 17:
Elution flow rate changes 1bV/h into, and all the other finally obtain 99.2% hydroxyl radical carthamin yellow carthamus A 1.45g with embodiment 1.(yield 85.3%)
Embodiment 18:
Elution flow rate changes 5bV/h into, and all the other finally obtain 99.1% hydroxyl radical carthamin yellow carthamus A 1.40g with embodiment 1.(yield 82.3%)
Comparative example 10:
Elution flow rate changes 0.5bV/h into, and all the other finally obtain 99.0% hydroxyl radical carthamin yellow carthamus A 1.28g with embodiment 1.(yield 75.3%)
Comparative example 11:
Elution flow rate changes 6bV/h into, and all the other finally obtain 99.0% hydroxyl radical carthamin yellow carthamus A 1.02g with embodiment 1.(yield 60.0%)
Above content is only to operational path example of the present invention and explanation; affiliated those skilled in the art make various modifications to described specific embodiment or supplement or adopt similar mode to substitute; only otherwise depart from the design of invention or surmount this scope as defined in the claims, all should belong to protection scope of the present invention.
Claims (9)
1. a preparation method for hydroxyl radical carthamin yellow carthamus A, is characterized in that, comprises the steps:
1) take the solution of Flos Carthami extract or hydroxyl radical carthamin yellow carthamus A crude product is raw material, regulates pH value to 6～9 as sample solution;
2) by step 1) sample solution add macroporous adsorptive resins, using water or lower concentration alcohol as elutriant wash-out, collect effluent liquid;
3) concentrate drying obtains pure hydroxyl radical carthamin yellow carthamus A.
2. the preparation method of hydroxyl radical carthamin yellow carthamus A according to claim 1, is characterized in that step 1) the pH value of raw material is adjusted to 9.
3. the preparation method of hydroxyl radical carthamin yellow carthamus A according to claim 1 and 2, is characterized in that step 2) in, sample solution is 1～2:1 with the weight resin ratio of macroporous adsorptive resins.
4. according to the preparation method of the arbitrary described hydroxyl radical carthamin yellow carthamus A of claim 1-2, it is characterized in that step 2) in, described macroporous adsorptive resins aspect ratio is 5～10:1.
5. the preparation method of hydroxyl radical carthamin yellow carthamus A according to claim 1, is characterized in that, described loading flow velocity is 1～5bV/h.
6. the preparation method of hydroxyl radical carthamin yellow carthamus A according to claim 1, is characterized in that, described elutriant is deionized water, distilled water, or is methyl alcohol or the ethanol of lower concentration.
7. the preparation method of hydroxyl radical carthamin yellow carthamus A according to claim 6, is characterized in that, described methanol concentration is 0～15%, and described alcohol concn is 0～10%.
8. the preparation method of hydroxyl radical carthamin yellow carthamus A according to claim 1, is characterized in that, described elution flow rate is 1～5bV/h.
9. the preparation method of hydroxyl radical carthamin yellow carthamus A according to claim 1, is characterized in that, specifically comprises the steps:
1) get flos carthami, add 10% ethanol, 40 ℃ of supersound extraction twice, each 1h, extracting liquid filtering, merging filtrate, concentrated, adopt 2M sodium hydroxide regulate concentrated solution to pH=9 as sample solution;
2) sample solution adsorbs than macroporous adsorptive resins in the ratio of 1:1 with weight resin, macroporous adsorptive resins aspect ratio 10:1, loading flow velocity is 2bV/h, after upper prop absorption, adopt deionized water wash-out, elution flow rate is 2bV/h, collects effluent liquid, HPLC detects effluent liquid, merges purity and surpasses 99% effluent liquid;
3) concentrated, the lyophilize of low-voltage vacuum, finally obtains highly purified hydroxyl radical carthamin yellow carthamus A powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410355732.2A CN104109178B (en) | 2014-07-24 | A kind of preparation method of S-A Hydroxysafflor yellow A |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410355732.2A CN104109178B (en) | 2014-07-24 | A kind of preparation method of S-A Hydroxysafflor yellow A |
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| CN104109178A true CN104109178A (en) | 2014-10-22 |
| CN104109178B CN104109178B (en) | 2017-01-04 |
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| CN106189351A (en) * | 2016-07-18 | 2016-12-07 | 唐翔 | A kind of process extracting safflower yellow from Flos Carthami |
| CN113816933A (en) * | 2021-10-14 | 2021-12-21 | 北京悦康科创医药科技股份有限公司 | Preparation method of hydroxysafflor yellow A |
| WO2022247860A1 (en) * | 2021-05-26 | 2022-12-01 | 台州永健医药科技有限公司 | Novel crystal form of hydroxysafflor yellow a and preparation method therefor |
| CN115677638A (en) * | 2018-12-25 | 2023-02-03 | 浙江永宁药业股份有限公司 | Safflower yellow and application thereof in preparing medicine for treating cardiovascular and cerebrovascular diseases |
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| CN101628022A (en) * | 2009-08-18 | 2010-01-20 | 山西德元堂药业有限公司 | Safflower dripping pill and preparation method thereof |
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| CN1704079A (en) * | 2004-05-31 | 2005-12-07 | 四川远大蜀阳药业有限公司 | Pharmaceutical composition for treating coronary heart disease and ischemia cerebral apoplexy and its preparation method |
| CN101628022A (en) * | 2009-08-18 | 2010-01-20 | 山西德元堂药业有限公司 | Safflower dripping pill and preparation method thereof |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106189351A (en) * | 2016-07-18 | 2016-12-07 | 唐翔 | A kind of process extracting safflower yellow from Flos Carthami |
| CN115677638A (en) * | 2018-12-25 | 2023-02-03 | 浙江永宁药业股份有限公司 | Safflower yellow and application thereof in preparing medicine for treating cardiovascular and cerebrovascular diseases |
| CN115677638B (en) * | 2018-12-25 | 2023-11-14 | 浙江永宁药业股份有限公司 | Carthamin yellow and application thereof in preparing medicine for treating cardiovascular and cerebrovascular diseases |
| WO2022247860A1 (en) * | 2021-05-26 | 2022-12-01 | 台州永健医药科技有限公司 | Novel crystal form of hydroxysafflor yellow a and preparation method therefor |
| CN113816933A (en) * | 2021-10-14 | 2021-12-21 | 北京悦康科创医药科技股份有限公司 | Preparation method of hydroxysafflor yellow A |
| CN113816933B (en) * | 2021-10-14 | 2024-02-09 | 北京悦康科创医药科技股份有限公司 | Preparation method of hydroxysafflor yellow A |
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