CN105481711A - Hydroxy-beta-sanshool monomer preparation method - Google Patents
Hydroxy-beta-sanshool monomer preparation method Download PDFInfo
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- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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Abstract
The invention provides a hydroxy-beta-sanshool monomer preparation method and belongs to the technical field of natural drug extraction. The preparation method effectively realizes extraction of a high-concentration hydroxy-beta-sanshool monomer from a Chinese prickly ash raw material. The preparation method comprises 1, extracting a hydroxysanshool mixture, 2, carrying out enrichment and pressure reduction condensation on the hydroxysanshool mixture to obtain hydroxysanshool mixture extract, 3, transforming hydroxy-beta-sanshool to improve hydroxy-beta-sanshool content of the hydroxysanshool mixture extract solution, 4, purifying the hydroxy-beta-sanshool to obtain a hydroxy-beta-sanshool monomer with purity of 70% or more, and 5, carrying out recrystallization to obtain a hydroxy-beta-sanshool monomer with purity of 98% or more. The preparation method is mainly used for preparing the hydroxy-beta-sanshool monomer.
Description
Technical field
The invention belongs to natural drug extractive technique field.
Background technology
Chinese prickly ash (ZanthoxylumL.) is Rutaceae (Rutaceae) Zanthoxylum (ZanthoxylumLinn) plant.Pericarpium Zanthoxyli fruit is one of China's traditional " eight large seasonings ", and its pungent numb taste is main flavor characteristic, is also most important quality parameter.In addition Chinese prickly ash Ye Shi China conventional Chinese medicine, can be used for treatment vomiting, diarrhoea, ascariasis etc., external application can treat eczema sufferings, promoting blood circulation to remove blood stasis, and all has obvious pharmacologically active to the treatment of cardiovascular system diseases and analgesia, calmness, anti-inflammatory, the aspect such as antibacterial.
Fagaramide is mostly chain unsaturated fatty acids amide structure, and the main component of to be wherein representative with sanshool be Chinese prickly ash fiber crops taste, has effects such as stimulating TRPV1, TRPA1.In Chinese prickly ash, amide substance is mainly hydroxyl-alpha-sanshool and hydroxy-beta-sanshool, but due to hydroxyl-alpha-sanshool instability, does not meet standard substance requirement, do not possess the condition as numb taste reference.Hydroxy-beta-sanshool is less slightly relative to hydroxyl-alpha-sanshool content, but relatively stable, can be prepared into Chinese prickly ash fiber crops taste reference.Hydroxy-beta-sanshool, has narcoticness sharp flavor, and be that Chinese prickly ash produces one of topmost active compound of numb taste mechanism of action, be present in the fruit of rutaceae Chinese pepper and pericarpium zanthoxyli, its molecular formula is C
16h
25nO
2.High woods good fortune waits people once to disclose Chinese patent application on November 13rd, 2012, name is called " manufacture method of the extract of hydroxyl sanshool " (application publication number: CN201210452421.9), has invented the extracting method of the hydroxyl sanshool mixture of low levels.The people such as Zhao Zhifeng once disclosed Chinese patent application on 05 31st, 2012, name is called, and " " (application publication number: CN201210175527.9) has invented the method extracting hydroxyl sanshool mixture to a kind of method extracting hydroxyl sanshool from Fructus Zanthoxyli oil.At present about the extraction preparation method of numb-taste components mainly utilizes supercritical CO
2extracting and separating goes out numb-taste components sanshool, extract is mostly xanthoxylum oleoresin or essential oil, only can obtain the hydroxyl sanshool mixed, and separation and purification efficiently can not obtain the hydroxy-beta-sanshool monomer of Chinese prickly ash, largely limit the Study and appliance of numb-taste components.
Summary of the invention
The object of this invention is to provide the preparation method of a kind of hydroxy-beta-sanshool monomer, it can extract hydroxy-beta-sanshool monomer effectively in Chinese prickly ash raw material.
Another object of the object of the invention is to provide the preparation method of a kind of hydroxy-beta-sanshool monomer, and it can prepare purity higher hydroxy-beta-sanshool monomer effectively.
The object of the invention is to be achieved through the following technical solutions: comprise the extraction of subject matter, enrichment, step of preparation process is as follows:
The extraction of step one, hydroxyl sanshool mixture
By dry Chinese prickly ash peel crushing, Extraction solvent volume fraction is that the aqueous solution of the lower alcohol of more than 85% carries out cold soaking extraction to Chinese prickly ash pericarp powder, liquid ratio is 1:5 ~ 1:10, extraction time is 48h, extracts 2 ~ 3 times, merges vat liquor, abandon the dregs of a decoction, vat liquor concentrating under reduced pressure obtains concentrated solution, and the volume of concentrated solution is 1/5 ~ 1/4 of vat liquor, obtains hydroxyl sanshool mixture;
The enrichment of step 2, hydroxyl sanshool mixture
The hydroxyl sanshool mixture of step one gained is diluted with water to low-alcohol solution volume fraction 10% ~ 20%, separation and purification is carried out by non-polar polystyrene type macroporous adsorbent resin column chromatography, dry Chinese prickly ash fruit weight and macroporous adsorbent resin volume ratio are 1Kg:0.5 ~ 1L, dynamic adsorption loading, rate of adsorption controls at 2.0BV ~ 3.0BV per hour, after absorption, first use the water of 2.0BV ~ 3.0BV and the low-alcohol solution wash-out removal of impurities of 50% ~ 60% respectively, use the low-alcohol solution wash-out of 85% ~ 95% of 2.5BV ~ 4.0BV again, collect elutriant, concentrating under reduced pressure obtains hydroxyl sanshool mixture medicinal extract.
The conversion of step 3, hydroxy-beta-sanshool
Because in the hydroxyl sanshool mixture medicinal extract of step 2 gained, hydroxyl-alpha-sanshool is higher than hydroxy-beta-Chinese pepper content, need to be transformed by the reaction of double bond cis-trans isomerism, by hydroxyl sanshool mixture medicinal extract organic solvent dissolution, add iodine and carry out the reaction of double bond cis-trans isomerization as catalyzer, after molecular balance, part of hydroxyl-α-sanshool changes into hydroxy-beta-sanshool, and reaction formula is as follows:
The content of hydroxy-beta-sanshool in hydroxyl sanshool mixture medicinal extract solution is improve after reaction.
The purifying of step 4, hydroxy-beta-sanshool
Step 3 gained hydroxyl sanshool mixture medicinal extract solution is positioned over cryogenic freezing crystallization in refrigerator, and filtration drying obtains hydroxy-beta-sanshool monomer that purity reaches more than 70%;
Low-alcohol solution described in step one is one or more mixture of methyl alcohol, ethanol.
Non-polar polystyrene type macroporous resin model described in step 2 is D101, AB-8, HP20.
Organic solvent described in step 3 is one or more the mixture in sherwood oil, acetone, ethyl acetate.
Another object of object of the present invention is achieved through the following technical solutions: the preparation method of a kind of hydroxy-beta-sanshool monomer, comprises the step one ~ step 3 repeating above-mentioned process:
The extraction of step one, hydroxyl sanshool mixture
By dry Chinese prickly ash peel crushing, Extraction solvent volume fraction is that the aqueous solution of the lower alcohol of more than 85% carries out cold soaking extraction to Chinese prickly ash pericarp powder, liquid ratio is 1:5 ~ 1:15, extraction time is 48h, extracts 2 ~ 3 times, merges vat liquor, abandon the dregs of a decoction, vat liquor concentrating under reduced pressure obtains concentrated solution, and the volume of concentrated solution is 1/5 ~ 1/4 of vat liquor, obtains hydroxyl sanshool mixture.
The enrichment of step 2, hydroxyl sanshool mixture
It is 10% ~ 20% that the hydroxyl sanshool mixture of step one gained is diluted with water to lower alcohol volume fraction, separation and purification is carried out by non-polar polystyrene type macroporous adsorbent resin column chromatography, dry Chinese prickly ash fruit weight and macroporous adsorbent resin volume ratio are 1Kg:0.5L ~ 1L, dynamic adsorption loading, rate of adsorption controls at 2.0BV ~ 3.0BV per hour, after absorption, first use the water of 2.0BV ~ 3.0BV and the low-alcohol solution wash-out removal of impurities of 50% ~ 60% respectively, use the low-alcohol solution wash-out of the 85%-95% of 2.5BV ~ 4.0BV again, collect elutriant, concentrating under reduced pressure obtains hydroxyl sanshool mixture medicinal extract.
The conversion of step 3, hydroxy-beta-sanshool
Because in the hydroxyl sanshool mixture medicinal extract of step 2 gained, hydroxyl-alpha-sanshool is higher than hydroxy-beta-Chinese pepper content, need to be transformed by the reaction of double bond cis-trans isomerism, by hydroxyl sanshool mixture medicinal extract organic solvent dissolution, add iodine and carry out the reaction of double bond cis-trans isomerization as catalyzer, after molecular balance, part of hydroxyl-α-sanshool changes into hydroxy-beta-sanshool, and reaction formula is as follows:
The content of hydroxy-beta-sanshool in hydroxyl sanshool mixture medicinal extract solution is improve after reaction.
The purifying of step 4, hydroxy-beta-sanshool
Hydroxyl sanshool mixture medicinal extract solution step 3 obtained is positioned over cryogenic freezing crystallization in refrigerator, and filtration drying obtains hydroxy-beta-sanshool monomer that purity reaches more than 70%.
Step 5, recrystallization
By hydroxy-beta-sanshool mixture medicinal extract organic solvent dissolution, freezing placement, crystallization, filtration drying, obtains hydroxy-beta-sanshool monomer that purity reaches more than 98%.
Lower alcohol described in step one is one or more the mixture in methyl alcohol, ethanol.
Non-polar polystyrene type macroporous resin model described in step 2 is D101, AB-8, HP20.
Organic solvent described in step 3 is one or more the mixture in sherwood oil, acetone, ethyl acetate.
Organic solvent described in step 5 is one or more the mixture in sherwood oil, acetone, ethyl acetate.
Advantage compared with prior art and effect:
One, the inventive method can obtain highly purified hydroxy-beta-sanshool monomer by extraction, enrichment, conversion, purifying and recrystallization five steps.Whole preparation process mild condition, top temperature is no more than 60 DEG C, ensure that the stability of hydroxy-beta-sanshool, and yield is high, easy and simple to handle, low to operator's technical requirements, is applicable to industrialization promotion.
Two, the product purity of gained of the present invention is high, and obtained hydroxy-beta-sanshool monomer purity can reach more than 98%.Filled up current Chinese prickly ash fiber crops degree detect and in Chinese prickly ash Quality Detection hydroxy-beta-sanshool as the blank of reference.
Three, the equipment that uses of the inventive method mainly, chromatography column during column chromatography, Rotary Evaporators during concentrating under reduced pressure, chromatography column and Rotary Evaporators cheap, and production cost is low.
Accompanying drawing explanation
Fig. 1 is the efficient liquid phase chromatographic analysis figure of hydroxy-beta-sanshool monomer that the embodiment of the present invention 5 obtains, and in figure, t=17.52min peak is hydroxy-beta-sanshool.
Fig. 2 is the hydrogen nuclear magnetic resonance spectrogram of hydroxy-beta-sanshool monomer that the embodiment of the present invention 5 obtains.
Fig. 3 is the carbon-13 nmr spectra figure of hydroxy-beta-sanshool monomer that the embodiment of the present invention 5 obtains.
Embodiment
Embodiment 1
A preparation method for hydroxy-beta-sanshool monomer, comprises the steps:
(1) the extraction of hydroxyl sanshool mixture
Get dry Chinese prickly ash pericarp 2kg broken, with the aqueous solution lixiviate 48h that volume fraction is 95% ethanol, liquid ratio is 1:10, extract 3 times, merge vat liquor, abandon the dregs of a decoction, vat liquor concentrating under reduced pressure at 50 DEG C of temperature obtains concentrated solution, the volume of concentrated solution is 1/5 of vat liquor, obtains hydroxyl sanshool mixture and fagaramide crude product.
(2) the enrichment of hydroxyl sanshool mixture
By step, (2) the fagaramide crude product of gained is diluted with water to volume fraction of ethanol is 20%, separation and purification is carried out by D101 type macroporous adsorbent resin column chromatography, macroporous adsorbent resin volume and dry Chinese prickly ash fruit weight ratio are 1Kg:1L, dynamic adsorption loading, rate of adsorption controls at 2.0BV per hour, after absorption, first use the water of 2.0BV and the ethanolic soln wash-out removal of impurities of 50% respectively, use the ethanolic soln wash-out of 85% of 2.5BV again, collect elutriant, at 50 DEG C of temperature, concentrating under reduced pressure obtains medicinal extract 70g.
(3) the conversion of hydroxy-beta-sanshool
Because in the hydroxyl sanshool mixture medicinal extract of step (2) gained, hydroxyl-alpha-sanshool is higher than hydroxy-beta-Chinese pepper content, transform so need to carry out double-bond isomerism reaction, hydroxyl sanshool mixture medicinal extract is dissolved with sherwood oil acetone (1:1) mixing solutions, detecting hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio in this solution known by HPLC is 2.55:1, 0.9% iodine adding this solution carries out double-bond isomerism reaction as catalyzer, after 20 DEG C of reaction 9h, part of hydroxyl-α-sanshool changes into hydroxy-beta-sanshool, detecting hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio in known solution by HPLC is 1:2.97.
(4) the purifying of hydroxy-beta-sanshool
Reacted for double-bond isomerism hydroxyl sanshool mixture medicinal extract solution is positioned over cryogenic freezing 18h in refrigerator, crystallization, and filtration drying obtains hydroxy-beta-sanshool monomer 2.0g that purity reaches 78.2%.
Embodiment 2
A preparation method for hydroxy-beta-sanshool monomer, comprises the steps:
(1) the extraction of hydroxyl sanshool mixture
Get dry Chinese prickly ash pericarp 2kg broken, with the flooding 48h that volume fraction is 85% ethanol, liquid ratio is 1:8, extract 3 times, merge vat liquor, abandon the dregs of a decoction, vat liquor concentrating under reduced pressure at 50 DEG C of temperature obtains concentrated solution, the volume of concentrated solution is 1/5 of vat liquor, obtains hydroxyl sanshool mixture and fagaramide crude product.
(2) the enrichment of hydroxyl sanshool mixture
By step, (2) the fagaramide crude product of gained is diluted with water to volume fraction of ethanol is 20%, separation and purification is carried out by HP-20 type macroporous adsorbent resin column chromatography, macroporous adsorbent resin volume and dry Chinese prickly ash fruit weight ratio are 1Kg:0.7L, dynamic adsorption loading, rate of adsorption controls at 2.5BV per hour, after absorption, first use the water of 2.5BV and the ethanolic soln wash-out removal of impurities of 55% respectively, use the ethanolic soln wash-out of 85% of 3BV again, collect elutriant, at 50 DEG C of temperature, concentrating under reduced pressure obtains medicinal extract 65g.
(3) the conversion of hydroxy-beta-sanshool
Because in the hydroxyl sanshool mixture medicinal extract of step (2) gained, hydroxyl-alpha-sanshool is higher than hydroxy-beta-Chinese pepper content, transform so need to carry out double-bond isomerism reaction, hydroxyl sanshool mixture medicinal extract is dissolved with sherwood oil acetone (2:1) mixing solutions, detecting hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio in known solution by HPLC is 2.31:1, 0.1% iodine adding solution carries out double-bond isomerism reaction as catalyzer, after 35 DEG C of reaction 12h, part of hydroxyl-α-sanshool changes into hydroxy-beta-sanshool, detecting hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio in known solution by HPLC is 1:2.72.
(4) the purifying of hydroxy-beta-sanshool
Reacted for double-bond isomerism hydroxyl sanshool mixture medicinal extract solution is positioned over cryogenic freezing 24h in refrigerator, crystallization, and filtration drying obtains hydroxy-beta-sanshool monomer 1.7g that purity reaches 72.3%.
Embodiment 3
A kind of hydroxy-beta-sanshool method for preparing monomer, comprises the steps:
(1) the extraction of hydroxyl sanshool mixture
Get dry Chinese prickly ash pericarp 2kg broken, with the flooding 48h that volume fraction is 90% methyl alcohol, liquid ratio is 1:10, extract 3 times, merge vat liquor, abandon the dregs of a decoction, vat liquor concentrating under reduced pressure at 50 DEG C of temperature obtains concentrated solution, the volume of concentrated solution is 1/5 of vat liquor, obtains hydroxyl sanshool mixture and fagaramide crude product.
(2) the enrichment of hydroxyl sanshool mixture
By step, (2) the fagaramide crude product of gained is diluted with water to methyl alcohol volume fraction is 15%, separation and purification is carried out by AB--8 type macroporous adsorbent resin column chromatography, macroporous adsorbent resin volume and dry Chinese prickly ash fruit weight ratio are 1Kg:1L, dynamic adsorption loading, rate of adsorption controls at 2.5BV per hour, after absorption, first use the water of 2.5BV and the methanol solution wash-out removal of impurities of 55% respectively, use the methanol solution wash-out of 85% of 3BV again, collect elutriant, at 50 DEG C of temperature, concentrating under reduced pressure obtains medicinal extract 58g.
(3) the conversion of hydroxy-beta-sanshool
Because in the hydroxyl sanshool mixture medicinal extract of step (2) gained, hydroxyl-alpha-sanshool is higher than hydroxy-beta-Chinese pepper content, transform so need to carry out double-bond isomerism reaction, hydroxyl sanshool mixture medicinal extract is dissolved with ethyl acetate solution, detecting hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio in this solution known by HPLC is 2.41:1, 0.5% iodine adding solution carries out double-bond isomerism reaction as catalyzer, after 40 DEG C of reaction 15h, part of hydroxyl-α-sanshool changes into hydroxy-beta-sanshool, detecting hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio in known solution by HPLC is 1:2.9.
(4) the purifying of hydroxy-beta-sanshool
Reacted for double-bond isomerism hydroxyl sanshool mixture medicinal extract solution is positioned over cryogenic freezing 36h in refrigerator, crystallization, and filtration drying obtains hydroxy-beta-sanshool monomer 1.5g that purity reaches 71.0%.
Embodiment 4
A preparation method for hydroxy-beta-sanshool monomer, comprises the steps:
(1) the extraction of hydroxyl sanshool mixture
Get dry Chinese prickly ash pericarp 2kg broken, be pure methyl alcohol lixiviate 48h by volume fraction, liquid ratio is 1: 8, extract 3 times, merge vat liquor, abandon the dregs of a decoction, vat liquor concentrating under reduced pressure at 50 DEG C of temperature obtains concentrated solution, the volume of concentrated solution is 1/5 of vat liquor, obtains hydroxyl sanshool mixture and fagaramide crude product.
(2) the enrichment of hydroxyl sanshool mixture
By step, (2) the fagaramide crude product of gained is diluted with water to methyl alcohol volume fraction is 20%, separation and purification is carried out by D101 type macroporous adsorbent resin column chromatography, macroporous adsorbent resin volume and dry Chinese prickly ash fruit weight ratio are 1Kg:0.7L, dynamic adsorption loading, rate of adsorption controls at 2.5BV per hour, after absorption, first use the water of 2.5BV and the methanol solution wash-out removal of impurities of 55% respectively, use the methanol solution wash-out of 85% of 3BV again, collect elutriant, at 50 DEG C of temperature, concentrating under reduced pressure obtains medicinal extract 65g.
(3) the conversion of hydroxy-beta-sanshool
Because in the hydroxyl sanshool mixture medicinal extract of step (2) gained, hydroxyl-alpha-sanshool is higher than hydroxy-beta-Chinese pepper content, transform so need to carry out double-bond isomerism reaction, hydroxyl sanshool mixture medicinal extract is dissolved with sherwood oil acetone (2:1) mixing solutions, detecting hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio in this solution known by HPLC is 2.31:1, 0.05% iodine adding this solution carries out double-bond isomerism reaction as catalyzer, after 20 DEG C of reaction 10h, part of hydroxyl-α-sanshool changes into hydroxy-beta-sanshool, detecting hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio in known solution by HPLC is 1:2.72.
(4) the purifying of hydroxy-beta-sanshool
Reacted for double-bond isomerism hydroxyl sanshool mixture medicinal extract solution is positioned over cryogenic freezing 20h in refrigerator, crystallization, and filtration drying obtains hydroxy-beta-sanshool monomer 1.7g that purity reaches 72.3%.
Embodiment 5
A preparation method for hydroxy-beta-sanshool monomer, comprises the steps:
(1) the extraction of hydroxyl sanshool mixture
Get dry Chinese prickly ash pericarp 10kg broken, be pure methyl alcohol lixiviate 48h by volume fraction, liquid ratio is 1:5, extract 3 times, merge vat liquor, abandon the dregs of a decoction, vat liquor concentrating under reduced pressure at 50 DEG C of temperature obtains concentrated solution, the volume of concentrated solution is 1/4 of vat liquor, obtains hydroxyl sanshool mixture and fagaramide crude product.
(2) the enrichment of hydroxyl sanshool mixture
By step, (1) the fagaramide crude product of gained is diluted with water to methyl alcohol volume fraction is 10%, separation and purification is carried out by AB-8 type macroporous adsorbent resin column chromatography, macroporous adsorbent resin volume and dry Chinese prickly ash fruit weight ratio are 1Kg:0.5L, dynamic adsorption loading, rate of adsorption controls at 3.0BV per hour, after absorption, first use the water of 3.0BV and the methanol solution wash-out removal of impurities of 60% respectively, use the methanol solution wash-out of 90% of 3.0BV again, collect elutriant, at 50 DEG C of temperature, concentrating under reduced pressure obtains medicinal extract 150g;
(3) the conversion of hydroxy-beta-sanshool
Because in the hydroxyl sanshool mixture medicinal extract of step (2) gained, hydroxyl-alpha-sanshool is higher than hydroxy-beta-Chinese pepper content, transform so need to carry out double-bond isomerism reaction, hydroxyl sanshool mixture medicinal extract is dissolved with sherwood oil acetone (0.5:1) mixing solutions, detecting hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio in this solution known by HPLC is 2.47:1, 1% iodine adding this solution carries out double-bond isomerism reaction as catalyzer, after 25 DEG C of reaction 8h, part of hydroxyl-α-sanshool changes into hydroxy-beta-sanshool, in solution, hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 1:2.87.
(4) the purifying of hydroxy-beta-sanshool
Reacted for double-bond isomerism hydroxyl sanshool mixture medicinal extract solution is positioned over cryogenic freezing 48h in refrigerator, crystallization, and filtration drying obtains hydroxy-beta-sanshool monomer 13g that purity reaches 79%;
(5) by step (4) gained hydroxy-beta-sanshool monomer acetone solution, freezing placement 8h, crystallization, filtration drying, obtain hydroxy-beta-sanshool monomer 8.1g, utilize high phase liquid chromatography (HPLC) to detect the purity of hydroxyl β-sanshool monomer that this example obtains, recording its purity is 99.4%.
Embodiment 6
A preparation method for hydroxy-beta-sanshool monomer, comprises the steps:
(1) the extraction of hydroxyl sanshool mixture
Get dry Chinese prickly ash pericarp 10kg broken, with the water alcohol lixiviate 48h that volume fraction is 95% ethanol, liquid ratio is 1:15, extract 3 times, merge vat liquor, abandon the dregs of a decoction, vat liquor concentrating under reduced pressure at 50 DEG C of temperature obtains concentrated solution, the volume of concentrated solution is 1/4 of vat liquor, obtains hydroxyl sanshool mixture and fagaramide crude product.
(2) the enrichment of hydroxyl sanshool mixture
By step, (1) the fagaramide crude product of gained is diluted with water to methyl alcohol volume fraction is 10%, separation and purification is carried out by D101 type macroporous adsorbent resin column chromatography, macroporous adsorbent resin volume and dry Chinese prickly ash fruit weight ratio are 1Kg:0.5L, dynamic adsorption loading, rate of adsorption controls at 2.0BV per hour, after absorption, first use the water of 2.0BV and the ethanolic soln wash-out removal of impurities of 50% respectively, use the ethanolic soln wash-out of 95% of 4.0BV again, collect elutriant, at 50 DEG C of temperature, concentrating under reduced pressure obtains medicinal extract 134g;
(3) the conversion of hydroxy-beta-sanshool
Because in the hydroxyl sanshool mixture medicinal extract of step (2) gained, hydroxyl-alpha-sanshool is higher than hydroxy-beta-Chinese pepper content, transform so need to carry out double-bond isomerism reaction, with sherwood oil: ethyl acetate (1:5) mixing solutions dissolves hydroxyl sanshool mixture medicinal extract, detecting hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio in this solution known by HPLC is 2.3:1, 2% iodine adding this solution carries out double-bond isomerism reaction as catalyzer, 10 DEG C of reactions are after 36 hours, part of hydroxyl-α-sanshool changes into hydroxy-beta-sanshool, in solution, hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 1:2.73.
(4) the purifying of hydroxy-beta-sanshool
Reacted for double-bond isomerism hydroxyl sanshool mixture medicinal extract solution is positioned over cryogenic freezing 10h in refrigerator, crystallization, and filtration drying obtains hydroxy-beta-sanshool monomer 11g that purity reaches 73.4%.
By step (4) gained hydroxy-beta-sanshool monomer sherwood oil ethyl acetate (1:2) dissolve, freezing placement 8h, crystallization, filtration drying, obtain hydroxy-beta-sanshool monomer 7g, utilize high phase liquid chromatography (HPLC) to detect the purity of hydroxyl β-sanshool monomer that this example obtains, recording its purity is 98.2%.
High performance liquid chromatography (HPLC) finished product hydroxy-beta-sanshool monomer to following embodiment is used to carry out purity detecting.Wherein chromatographic condition is: moving phase consists of methanol-water 70:3, chromatographic column model YMC-PackODS-A chromatographic column (4.6mm × 250mm, 5 μm); Flow velocity 1.0mL/min; Column temperature: room temperature; Determined wavelength 254nm.
Claims (9)
1. a preparation method for hydroxy-beta-sanshool monomer, comprises the extraction of subject matter, enrichment, it is characterized in that:
The extraction of step one, hydroxyl sanshool mixture
By dry Chinese prickly ash peel crushing, Extraction solvent volume fraction is that the aqueous solution of the lower alcohol of more than 85% carries out cold soaking extraction to Chinese prickly ash pericarp powder, liquid ratio is 1:5 ~ 1:10, extraction time is 48h, extracts 2 ~ 3 times, merges vat liquor, abandon the dregs of a decoction, vat liquor concentrating under reduced pressure obtains concentrated solution, and the volume of concentrated solution is 1/5 ~ 1/4 of vat liquor, obtains hydroxyl sanshool mixture;
The enrichment of step 2, hydroxyl sanshool mixture
The hydroxyl sanshool mixture of step one gained is diluted with water to low-alcohol solution volume fraction 10% ~ 20%, separation and purification is carried out by non-polar polystyrene type macroporous adsorbent resin column chromatography, dry Chinese prickly ash fruit weight and macroporous adsorbent resin volume ratio are 1Kg:0.5 ~ 1L, dynamic adsorption loading, rate of adsorption controls at 2.0BV ~ 3.0BV per hour, after absorption, first use the water of 2.0BV ~ 3.0BV and the low-alcohol solution wash-out removal of impurities of 50% ~ 60% respectively, use the low-alcohol solution wash-out of 85% ~ 95% of 2.5BV ~ 4.0BV again, collect elutriant, concentrating under reduced pressure obtains hydroxyl sanshool mixture medicinal extract,
The conversion of step 3, hydroxy-beta-sanshool
Because in the hydroxyl sanshool mixture medicinal extract of step 2 gained, hydroxyl-alpha-sanshool is higher than hydroxy-beta-Chinese pepper content, with organic solvent dissolution hydroxyl sanshool mixture medicinal extract, add iodine and carry out the reaction of double bond cis-trans isomerization as catalyzer, after molecular balance, part of hydroxyl-α-sanshool changes into hydroxy-beta-sanshool, and reaction formula is as follows:
This reaction can improve the content of hydroxy-beta-sanshool in hydroxyl sanshool mixture medicinal extract solution;
The purifying of step 4, hydroxy-beta-sanshool
Step 3 gained hydroxy-beta-sanshool mixture medicinal extract solution is positioned over cryogenic freezing crystallization in refrigerator, and filtration drying obtains hydroxy-beta-sanshool monomer that purity reaches more than 70%.
2. require the preparation method of described a kind of hydroxy-beta-sanshool monomer according to right 1, it is characterized in that, the low-alcohol solution described in step one is one or more mixture of methyl alcohol, ethanol.
3. require the preparation method of described a kind of hydroxy-beta-sanshool monomer according to right 1, it is characterized in that, the non-polar polystyrene type macroporous resin model described in step 2 is D101, AB-8, HP20.
4. require the preparation method of described a kind of hydroxy-beta-sanshool monomer according to right 1, it is characterized in that, organic solvent described in step 3 is one or more the mixture in sherwood oil, acetone, ethyl acetate.
5. a preparation method for hydroxy-beta-sanshool monomer, comprises the step one ~ step 3 of repetition claim 1:
The extraction of step one, hydroxyl sanshool mixture
By dry Chinese prickly ash peel crushing, Extraction solvent volume fraction is that the aqueous solution of the lower alcohol of more than 85% carries out cold soaking extraction to Chinese prickly ash pericarp powder, liquid ratio is 1:5 ~ 1:15, extraction time is 48h, extracts 2 ~ 3 times, merges vat liquor, abandon the dregs of a decoction, vat liquor concentrating under reduced pressure obtains concentrated solution, and the volume of concentrated solution is 1/5 ~ 1/4 of vat liquor, obtains hydroxyl sanshool mixture;
The enrichment of step 2, hydroxyl sanshool mixture
It is 10%-20% that the hydroxyl sanshool mixture of step one gained is diluted with water to lower alcohol volume fraction, separation and purification is carried out by non-polar polystyrene type macroporous adsorbent resin column chromatography, dry Chinese prickly ash fruit weight and macroporous adsorbent resin volume ratio are 1Kg:0.5 ~ 1L, dynamic adsorption loading, rate of adsorption controls at 2.0BV ~ 3.0BV per hour, after absorption, first use the water of 2.0BV ~ 3.0BV and the low-alcohol solution wash-out removal of impurities of 50% ~ 60% respectively, use the low-alcohol solution wash-out of 85% ~ 95% of 2.5BV ~ 4.0BV again, collect elutriant, concentrating under reduced pressure obtains hydroxyl sanshool mixture medicinal extract,
The conversion of step 3, hydroxy-beta-sanshool
Carry out the reaction of double bond cis-trans isomerization using adding iodine after the hydroxyl sanshool mixture medicinal extract organic solvent dissolution of step 2 gained as catalyzer, after molecular balance, part of hydroxyl-α-sanshool changes into hydroxy-beta-sanshool, and reaction formula is as follows:
This reaction can improve the content of hydroxy-beta-sanshool in hydroxyl sanshool mixture medicinal extract solution;
The purifying of step 4, hydroxy-beta-sanshool
Hydroxy-beta step 3 obtained-sanshool mixture medicinal extract solution is positioned over cryogenic freezing crystallization in refrigerator, and filtration drying obtains hydroxy-beta-sanshool monomer that purity reaches more than 70%;
Step 5, recrystallization
By obtain in step 4 more than 70% hydroxy-beta-sanshool monomer organic solvent dissolution, freezing placement, crystallization, filtration drying, obtains hydroxy-beta-sanshool monomer that purity reaches more than 98%.
6. the preparation method of a kind of hydroxy-beta-sanshool monomer according to claim 5, is characterized in that, the lower alcohol described in step one is one or more the mixture in methyl alcohol, ethanol.
7. the preparation method of a kind of hydroxy-beta-sanshool monomer according to claim 5, is characterized in that, the non-polar polystyrene type macroporous resin model described in step 2 is D101, AB-8, HP20.
8. the preparation method of a kind of hydroxy-beta-sanshool monomer according to claim 5, is characterized in that: the organic solvent described in step 3 is one or more the mixture in sherwood oil, acetone, ethyl acetate.
9. the preparation method of a kind of hydroxy-beta-sanshool monomer according to claim 5, is characterized in that: the organic solvent described in step 5 is one or more mixture of sherwood oil, acetone, ethyl acetate.
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| CN106866455A (en) * | 2015-12-11 | 2017-06-20 | 西南大学 | A kind of preparation method of high-purity numb-taste components |
| CN107033017A (en) * | 2017-04-25 | 2017-08-11 | 四川大学 | A kind of method of quick preparation high-purity hydroxyl γ sanshools |
| CN113816870A (en) * | 2021-08-25 | 2021-12-21 | 沈阳药科大学 | Method for rapidly extracting different sanshool monomers |
| CN113841745A (en) * | 2021-01-28 | 2021-12-28 | 丰益(上海)生物技术研发中心有限公司 | Zanthoxylum oil, preparation method and application thereof, and material using zanthoxylum oil |
| CN115286529A (en) * | 2022-08-05 | 2022-11-04 | 西南交通大学 | Stabilizer of hydroxy-alpha-sanshool and storage method |
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| CN106866455A (en) * | 2015-12-11 | 2017-06-20 | 西南大学 | A kind of preparation method of high-purity numb-taste components |
| CN106866455B (en) * | 2015-12-11 | 2019-11-19 | 西南大学 | A kind of preparation method of high-purity numb-taste components |
| CN106309671A (en) * | 2016-09-23 | 2017-01-11 | 甘肃中医药大学 | Gansu Longnan Zanthoxylum Bungeagum Maxim extract component and preparation and detection methods thereof |
| CN106309671B (en) * | 2016-09-23 | 2017-07-18 | 甘肃中医药大学 | Longnan of Gansu Province Z-bungeanum Maxim extract components and preparation method thereof and detection method |
| CN107033017A (en) * | 2017-04-25 | 2017-08-11 | 四川大学 | A kind of method of quick preparation high-purity hydroxyl γ sanshools |
| CN113841745A (en) * | 2021-01-28 | 2021-12-28 | 丰益(上海)生物技术研发中心有限公司 | Zanthoxylum oil, preparation method and application thereof, and material using zanthoxylum oil |
| CN113816870A (en) * | 2021-08-25 | 2021-12-21 | 沈阳药科大学 | Method for rapidly extracting different sanshool monomers |
| CN113816870B (en) * | 2021-08-25 | 2023-10-31 | 沈阳药科大学 | Method for rapidly extracting different sanshool monomers |
| CN115286529A (en) * | 2022-08-05 | 2022-11-04 | 西南交通大学 | Stabilizer of hydroxy-alpha-sanshool and storage method |
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