CN106083744A - A kind of method from Semen Podocarpi Macrophylli seed high efficiency extraction separating high-purity ligustrazine - Google Patents
A kind of method from Semen Podocarpi Macrophylli seed high efficiency extraction separating high-purity ligustrazine Download PDFInfo
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- CN106083744A CN106083744A CN201610460262.5A CN201610460262A CN106083744A CN 106083744 A CN106083744 A CN 106083744A CN 201610460262 A CN201610460262 A CN 201610460262A CN 106083744 A CN106083744 A CN 106083744A
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- C07—ORGANIC CHEMISTRY
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- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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Abstract
The present invention relates to a kind of method from Semen Podocarpi Macrophylli seed high efficiency extraction separating high-purity ligustrazine, the method step, for taking Semen Podocarpi Macrophylli seed meal, was soaked 30 minutes, with steam distillation heating extraction 6～9 hours, collect distillate, adding petroleum ether extraction, take petroleum ether layer decompression and solvent recovery, concentrated solution stands or sucking filtration after cold preservation, it is dried, obtain coarse crystallization, add water recrystallization, wash, be drying to obtain.Using the present invention to prepare ligustrazine, step is few, and the cycle is short, easy and simple to handle, high product purity, and equipment investment is few, and production cost can be greatly lowered.
Description
Technical field
The invention belongs to Chemistry for Chinese Traditional Medicine, Natural Medicine Chemistry and pharmaceutical technology field, be specifically related to a kind of from Semen Podocarpi Macrophylli kind
The method of high efficiency extraction separating and purifying high-purity ligustrazine in son.
Background technology
Semen Podocarpi Macrophylli is Podocarpaceae plant soil China fir Podocarpus macrophyllus (Thunb.) D.Don or short leaf soil
The seed of China fir Podocarpus macrophyllus (Thunb.) D.Don var.maki (Sieb.) Endl. and holder.Document
Recording, Semen Podocarpi Macrophylli has the kidney invigorating lung benefiting, controls blood deficiency shallow complexion, effect of heart stomachache.Semen Podocarpi Macrophylli is existing in Beihai, Guangxi
Fairly large plantation, cultivated area reaches 1.5 ten thousand mu, every year can the substantial amounts of Semen Podocarpi Macrophylli of output.The holder part of Semen Podocarpi Macrophylli can
Directly eat as fruit, or make list marketing after fruit wine or health promoting wine.But the seed fraction of Semen Podocarpi Macrophylli fails in addition
Comprehensive development and utilization, causes the waste of herb resource.Therefore, the seed fraction of Semen Podocarpi Macrophylli is carried out intensive processing research,
Make the best use of everything, reduce the wasting of resources, improve medical material added value, be problem the most in the urgent need to address.There are some researches show, arhat
Pine seed and the medicinal amino acid content of holder are higher, and rich in calcium, magnesium mineral element；Holder ethanol extract has blood fat reducing, antioxygen
Change and hepatoprotective effect.We have discovered that, Semen Podocarpi Macrophylli seed contains important medicinal ingredient ligustrazine, and this may have with it
There is the effect controlling heart stomachache relevant.
Ligustrazine, also known as tetramethylpyazine, for colorless needle crystals, has special foreign odor.Modern pharmacology research shows,
Ligustrazine have antiplatelet aggregation, increase coronary flow, improve microcirculation and increase cerebral blood flow effect.At present, ligustrazine
Can be obtained by following three kinds of approach: one is extraction separation and purification from Ligusticum chuanxiong Hort；Two is prepared by chemical synthesis；Three is profit
Prepare with microbe fermentation method.
The method preparing ligustrazine from Ligusticum chuanxiong Hort extraction separation and purification is more.Chinese invention patent
CN200910032515.9 and CN201010247117.1 discloses the preparation method of ligustrazine, and both approaches is returned by ethanol
Stream extracts, extraction, column chromatography and re-crystallization step obtain the purity product more than 90% repeatedly；Patent of invention
CN200810045194.1 discloses ligustrazine, ferulic acid and the method for volatile oil, this method in a kind of comprehensively extracting and purifying Rhizoma Chuanxiong
Separated by sour water reflux, extract, ion exchange resin column and the ligustrazine of extraction step acquisition purity about 80%.Above this
A little methods are required for column chromatographic isolation and purification, and repeatedly extract, and operating process is loaded down with trivial details, and the cycle is long, and, ligustrazine is in river
Content in rhizome of chuanxiong medical material is extremely low, and therefore, product yield is relatively low.Patent of invention CN201410572434.9 discloses a kind of supercritical
CO2Fluid prepares the method for ligustrazine from Rhizoma Chuanxiong, although this method advanced technology, but need special device pressurised extraction, and still need to
Column chromatographic isolation and purification, industrial applications is wanted to be limited by appointed condition.Chemical synthesis prepares ligustrazine, such as Chinese invention patent
Method disclosed in CN201410610247.5 and CN201410548902.9, although yield is higher, but need a large amount of organic solvent
And obtained by the regulation step such as pH or extraction.Biological synthesis process such as Chinese invention patent CN200910096814.9 and
Method disclosed in CN201010104264.3, need to use culture medium, and the microorganism culturing cycle is long, and condition requires harshness.
Summary of the invention
It is an object of the invention to for prior art exist preparation process loaded down with trivial details, the production cycle is long, product purity low or
Need to be by problems such as a large amount of chemical reagent, it is provided that a kind of new rapid extraction separates the method obtaining high-purity ligustrazine.This method work
Skill is easy, it is easy to controlling, extracting cycle is short, and obtained product purity is high, has more preferable industrial advantages.
Method of the present invention comprises the steps:
(1) extract: take Semen Podocarpi Macrophylli seed, be ground into the coarse powder of 10～30 mesh, add the water of quality of medicinal material 10～20 times amount,
Soak 30 minutes, with steam distillation heating extraction 6～9 hours, collect distillate；
(2) isolated and purified: to take distillate, addition petroleum ether extraction 2～3 times, add the volume of petroleum ether for distillating every time
Long-pending 0.5～2 times of liquid, merges the petroleum ether layer of 2～3 extractions, and record initial volume, in 30～60 DEG C of recovered under reduced pressure oil
Ether, when being more than or equal to the 95% of initial volume to the petroleum ether volume reclaimed, stops reclaiming, and it is little that concentrated solution room temperature stands 8～24
Time or in 0～10 DEG C of cold preservation 8～12 hours, sucking filtration, or naturally volatilize solvent or 30～60 DEG C be dried, obtain purity more than 95%
Ligustrazine crude product, crude product water recrystallization, wash, be drying to obtain purity more than 98% ligustrazine fine work.
Said extracted separation method, it is characterised in that the boiling range of petroleum ether described in step (2) be 30～60 DEG C or 60～
90℃。
The present invention extracts separating obtained ligustrazine crude product and fine work is colourless acicular crystal, and crude product is through gas chromatogram-string
Connection mass spectrum (GC-MS-MS) measures and carries out database search, and result identifies two compounds, and wherein main constituent is tetramethyl
Pyrazine, i.e. ligustrazine, molecular formula is C8H12N2, No. CAS: 1124-11-4, relative amount 97.27% (see accompanying drawing 1).Ligustrazine
Fine work uses high performance liquid chromatography (HPLC), measures purity with areas of peak normalization method, and result purity is 99.80% (see accompanying drawing
2).Ligustrazine fine work measures through micro-meldometer, and fusing point is 82.5～84.0 DEG C.Mass spectroscopy result shows, ligustrazine fine work
Mass spectrum consistent with standard diagram (see accompanying drawing 3).
The present invention compared with prior art has the advantage that
1, the present invention uses steam distillation extracting directly ligustrazine, with ethanol reflux extraction and supercritical CO2Stream
Body extraction is compared, and in the extract obtained, ligustrazine relative amount is higher, and other impurity component is few, it is easy to isolated and purified.
2, the isolated and purified process of ligustrazine of the present invention is not required to use column chromatography to separate, only by simple extraction
Obtaining high-purity ligustrazine, operating procedure is few, and the cycle is short, easy and simple to handle, and equipment investment is few, and production cost can be greatly lowered.
3, the present invention uses petroleum ether directly to extract distillate, and petroleum ether is big to ligustrazine dissolubility, and boiling point
Low, it is easy to recycle and reuse, reduce energy consumption, save solvent, environmental pollution is little.
Accompanying drawing explanation
Fig. 1 ligustrazine crude product GC-MS-MS measures total ion current figure
Fig. 2 HPLC areas of peak normalization method detection ligustrazine fine work purity chromatogram
Fig. 3 ligustrazine fine work mass spectrum
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is described in further details, but the scope of protection of present invention is also
It is not limited to the following example.
Embodiment 1
Take Semen Podocarpi Macrophylli seed 100g, go the removal of impurity, pulverize, cross 10 mesh sieves, put in round-bottomed flask, add quality of medicinal material 10
The water of times amount, soaks 30 minutes, by steam distillation, heating extraction 6 hours, collects distillate, puts in separatory funnel, adds
Boiling range is the petroleum ether extraction 2 times of 30～60 DEG C, each petroleum ether consumption and distillate equal-volume, merges the oil extracted 2 times
Ether layer, with Rotary Evaporators in 30 DEG C of recovered under reduced pressure petroleum ether, when being equal to the 99% of initial volume to the petroleum ether volume reclaimed,
Stopping reclaiming, concentrated solution volatilizes solvent naturally, obtains ligustrazine crystallization, and HPLC detection purity is 95.2%, uses water recrystallization, washes
Washing, being drying to obtain ligustrazine fine work 0.01g, HPLC detection purity is 98.5%.
Embodiment 2
Take Semen Podocarpi Macrophylli seed 100g, go the removal of impurity, pulverize, cross 10 mesh sieves, put in round-bottomed flask, add quality of medicinal material 15
The water of times amount, soaks 30 minutes, by steam distillation, heating extraction 8 hours, collects distillate, puts in separatory funnel, adds
Boiling range is the petroleum ether extraction 2 times of 30～60 DEG C, every time add that petroleum ether volume is distillate volume 1.5 times, merges 2 extractions
The petroleum ether layer taken, with Rotary Evaporators in 40 DEG C of recovered under reduced pressure petroleum ether, to the petroleum ether volume reclaimed equal to initial volume
98% time, stop reclaim, concentrated solution room temperature stand 12 hours, sucking filtration, obtain ligustrazine crystallization, HPLC detection purity be
96.4%, use water recrystallization, washing, being drying to obtain ligustrazine fine work 0.012g, HPLC detection purity is 99.5%.
Embodiment 3
Take Semen Podocarpi Macrophylli seed 100g, go the removal of impurity, pulverize, cross 10 mesh sieves, put in round-bottomed flask, add quality of medicinal material 20
The water of times amount, soaks 30 minutes, by steam distillation, heating extraction 9 hours, collects distillate, puts in separatory funnel, adds
Boiling range is the petroleum ether extraction 3 times of 30～60 DEG C, every time add that petroleum ether volume is distillate volume 0.5 times, merges 3 extractions
The petroleum ether layer taken, with Rotary Evaporators in 50 DEG C of recovered under reduced pressure petroleum ether, to the petroleum ether volume reclaimed equal to initial volume
95% time, stop reclaim, 4 DEG C of cold preservations of concentrated solution 8 hours, sucking filtration, obtain ligustrazine crystallization, HPLC detection purity be 96.0%,
Using water recrystallization, washing, being drying to obtain ligustrazine fine work 0.015g, HPLC detection purity is 99.0%.
Embodiment 4
Take Semen Podocarpi Macrophylli seed 100g, go the removal of impurity, pulverize, cross 16 mesh sieves, put in round-bottomed flask, add quality of medicinal material 12
The water of times amount, soaks 30 minutes, by steam distillation, heating extraction 7 hours, collects distillate, puts in separatory funnel, adds
Boiling range is the petroleum ether extraction 2 times of 30～60 DEG C, every time add that petroleum ether volume is distillate volume 2 times, merges 2 extractions
Petroleum ether layer, with Rotary Evaporators in 60 DEG C of recovered under reduced pressure petroleum ether, to the petroleum ether volume reclaimed equal to initial volume
When 97%, stopping reclaiming, concentrated solution 40 DEG C is dried, and obtains ligustrazine crystallization, and HPLC detection purity is 95.0%, uses water recrystallization,
Washing, being drying to obtain ligustrazine fine work 0.01g, HPLC detection purity is 98.0%.
Embodiment 5
Take Semen Podocarpi Macrophylli seed 100g, go the removal of impurity, pulverize, cross 24 mesh sieves, put in round-bottomed flask, add quality of medicinal material 18
The water of times amount, soaks 30 minutes, by steam distillation, heating extraction 9 hours, collects distillate, puts in separatory funnel, adds
Boiling range is the petroleum ether extraction 2 times of 30～60 DEG C, each petroleum ether consumption and distillate equal-volume, merges the oil extracted 2 times
Ether layer, with Rotary Evaporators in 45 DEG C of recovered under reduced pressure petroleum ether, when being equal to the 95% of initial volume to the petroleum ether volume reclaimed,
Stopping reclaiming, 10 DEG C of cold preservations of concentrated solution 12 hours, sucking filtration, obtain ligustrazine crystallization, HPLC detection purity is 95.7%, heavily ties with water
Crystalline substance, washing, being drying to obtain ligustrazine fine work 0.013g, HPLC detection purity is 99.2%.
Claims (2)
1. the method from Semen Podocarpi Macrophylli seed high efficiency extraction separating high-purity ligustrazine, it is characterised in that described method includes
The following step:
(1) extract: take Semen Podocarpi Macrophylli seed, be ground into the coarse powder of 10～30 mesh, add the water of quality of medicinal material 10～20 times amount, soak
30 minutes, with steam distillation heating extraction 6～9 hours, collect distillate；
(2) isolated and purified: to take distillate, addition petroleum ether extraction 2～3 times, add the volume of petroleum ether for distillating liquid every time
Long-pending 0.5～2 times, merges the petroleum ether layer of 2～3 extractions, records initial volume, in 30～60 DEG C of recovered under reduced pressure petroleum ether,
To reclaim petroleum ether volume more than or equal to initial volume 95% time, stop reclaim, concentrated solution room temperature stand 8～24 hours or
In 0～10 DEG C of cold preservation 8～12 hours, sucking filtration, naturally volatilize solvent or 30～60 DEG C be dried, obtain the purity river more than 95%
Rhizome of chuanxiong piperazine crude product, crude product water recrystallization, washs, is drying to obtain the purity ligustrazine fine work more than 98%.
The method of extraction separating high-purity ligustrazine the most according to claim 1, it is characterised in that stone described in step (2)
The boiling range of oil ether is 30～60 DEG C or 60～90 DEG C.
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| CN201610460262.5A CN106083744B (en) | 2016-06-23 | 2016-06-23 | A method of from podocarpus seed high efficiency extraction separating high-purity ligustrazine |
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| CN201610460262.5A CN106083744B (en) | 2016-06-23 | 2016-06-23 | A method of from podocarpus seed high efficiency extraction separating high-purity ligustrazine |
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| CN106083744B CN106083744B (en) | 2018-08-14 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109602759A (en) * | 2019-01-17 | 2019-04-12 | 广西医科大学 | The purposes of kusamaki broad-leaved podocarpus seed and receptacle polysaccharide |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110487938B (en) * | 2019-09-25 | 2022-01-11 | 广西医科大学 | Quality control method of podocarpus macrophyllus kurz medicinal material |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101503718A (en) * | 2009-03-16 | 2009-08-12 | 浙江大学 | Preparation of Tetramethylpyrazine |
| CN101602735A (en) * | 2009-07-01 | 2009-12-16 | 南京泽朗医药科技有限公司 | A kind of preparation method of Ligustrazine |
| CN102344417A (en) * | 2010-08-06 | 2012-02-08 | 苏州瑞蓝博中药技术开发有限公司 | Extraction method for ligustrazine |
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2016
- 2016-06-23 CN CN201610460262.5A patent/CN106083744B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101503718A (en) * | 2009-03-16 | 2009-08-12 | 浙江大学 | Preparation of Tetramethylpyrazine |
| CN101602735A (en) * | 2009-07-01 | 2009-12-16 | 南京泽朗医药科技有限公司 | A kind of preparation method of Ligustrazine |
| CN102344417A (en) * | 2010-08-06 | 2012-02-08 | 苏州瑞蓝博中药技术开发有限公司 | Extraction method for ligustrazine |
Non-Patent Citations (1)
| Title |
|---|
| 方欣等: "水蒸气蒸馏罗汉松精油工艺及有效成份分析", 《广州化工》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109602759A (en) * | 2019-01-17 | 2019-04-12 | 广西医科大学 | The purposes of kusamaki broad-leaved podocarpus seed and receptacle polysaccharide |
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