CN101993461A - Method for refining crude baicalin - Google Patents

Abstract

The invention discloses a method for refining crude baicalin and relates to the technology of glycosides extraction such as acid protection and alcohol precipitation and is used for refining baicalin. In the invention, alcohol, hydrochloric acid, sodium hydroxide and de-ionized water are adopted to remove impurities of different polarities stepwise, the obtained sample is baicalin exclusively, the purify of the baicalin is as high as over 99 percent, and the total transfer rate of the baicalin is over 85 percent.

Description

A kind of process for purification of baicalin crude product

Technical field

The present invention relates to a kind of process for purification of baicalin crude product, particularly, relate to a kind of method of alcohol precipitation separation and purification baicalin.

Background technology

The main purpose of Chinese medicine preparation production technique is active constituent-enriched, removes invalid impurity.Baicalin is one of effective constituent in the root of large-flowered skullcap, have antibacterial, antiviral, anti-inflammatory, step-down, calmness, protect the liver, cholagogic, etc. pharmacological action.Baicalin is content height (7.0-20%) in the root of large-flowered skullcap, traditional baicalin crude product extracts and adopts water to carry to add Acid precipitation and can propose, for example Zhai protects [Zhai Baotong on an equal basis, Wang Ying. the baicalin Study on extraction. Chinese Medicine Leader 2007,4 (23): 91-93] promptly adopt water to put forward the method that adds Acid precipitation, content of baicalin can reach 70-85% in the crude baicalin that obtains.

Further making with extra care on this basis to make content reach more than 90%, for example Chinese patent CN101475618A promptly adopts baicalin crude product alkali dissolution, add alcohol precipitation partial impurities, filter, with acid baicalin is precipitated out again, this process for purification can make content of baicalin increase to 92%, though can satisfy the production needs of injection liquid, but still contain a large amount of impurity, inevitably bring the untoward reaction and the quality problems of medicine.

Summary of the invention

The invention provides a kind of process for purification of baicalin, this baicalin process for purification may further comprise the steps:

A, baicalin crude product add water, heating in water bath stirs, and it is 6.0-7.0 that the hydro-oxidation sodium solution is regulated the pH value, and the baicalin crude product is dissolved fully, filter, after adding ethanol stirs evenly in the filtrate is 1.0-2.5 with the hydrochloric acid adjust pH immediately, heat tracing, and room temperature is placed, filter, with 40-60% washing with alcohol precipitation, filtration, drying get intermediate A then;

B, intermediate A add water, stir, and it is 6.0-7.0 that the hydro-oxidation sodium solution is regulated the pH value, make dissolving fully, filter, adding with the hydrochloric acid adjust pH in the filtrate is the ethanol of 1.0-3.0, stir evenly, or transfer PH4.0-6.0 with HCL immediately after adding ethanol, place, filter, precipitation adds water, stirs, after adding ethanol stirs evenly is pH1.0-2.5 with the hydrochloric acid tone pitch immediately, heat tracing, and room temperature is placed, filter, with 40-60% washing with alcohol precipitation, filter, get intermediate B then;

C, intermediate B add 40-60% ethanol and stir, and filter, and precipitation with the alcohol immersion washing, is filtered again, is drying to obtain the baicalin elaboration.

This baicalin process for purification step is preferably:

A, baicalin crude product add 5-15 and doubly measure (kg/L) water, heating in water bath stirs, add 10-40% sodium hydroxide solution adjusting pH value and be 6.0-7.0, the baicalin crude product is dissolved fully, filter, adding isopyknic ethanol in the filtrate is 1.0-2.5 with the hydrochloric acid adjust pH of 2-4mol/L immediately after stirring evenly, be heated to 40-85 ℃, be incubated 20-40 minute, room temperature was placed 10-20 hour, filtered, and precipitated with 1-5 times of baicalin crude product (kg/L) 40-60% washing with alcohol, suction filtration, drying get intermediate A then;

B, intermediate A adds 5-8 and doubly measures (kg/L) water, stir, it is 6.0-7.0 that the hydro-oxidation sodium solution is regulated the pH value, makes dissolving fully, filter, adding 4-8 times of volume in the filtrate is the ethanol of 1.0-3.0 with the hydrochloric acid adjust pH, stirs evenly, or transfers pH4.0-6.0 with HCL immediately after adding ethanol, place 1-3h, filter, precipitation adds water, stirs, adding isopyknic ethanol is 1.0-2.5 with the hydrochloric acid adjust pH immediately after stirring evenly, be heated to 40-85 ℃, insulation 5-30min, room temperature is placed 10-20h, filter, the 40-60% washing with alcohol of doubly measuring intermediate A (kg/L) with 1-5 precipitates, and filters, drying gets intermediate B;

C, intermediate B add 5-10 doubly to be measured (kg/L) 40-60% ethanol and stirs, and filters, and precipitation is doubly measured the 90-99% alcohol immersion washing of intermediate B (kg/L) again with 1-5, filter, and is drying to obtain the baicalin elaboration.

More preferably:

A, baicalin crude product add 8 times of amounts (kg/L) water, and heating in water bath stirs, and add 20% sodium hydroxide solution adjusting pH value and are 6.0-7.0, the baicalin crude product is dissolved fully, filter, adding isopyknic ethanol in the filtrate is 1.0-2.5 with the hydrochloric acid adjust pH of 2mol/L immediately after stirring evenly, and is heated to 50 ℃, be incubated 40 minutes, room temperature was placed 12 hours, filtered, and precipitated with 2 times of baicalin crude products (kg/L) 40-60% washing with alcohol, suction filtration, drying get intermediate A then;

B, intermediate A adds 6 times of amounts (kg/L) water, stir, it is 6.0-7.0 that the hydro-oxidation sodium solution is regulated the pH value, makes dissolving fully, filters, adding 4 times of volumes in the filtrate is the ethanol of 1.0-3.0 with the hydrochloric acid adjust pH, stir evenly, place 3h, filter, precipitation adds the water of 4 times of amount intermediate A (kg/L), stir, adding isopyknic 95% ethanol is 1.0-2.5 with 2mol/L hydrochloric acid adjust pH immediately after stirring evenly, and is heated to 40-85 ℃, heat tracing 5-30min, room temperature is placed 10-20h, filters, with the 50% washing with alcohol precipitation of 2 times of amount intermediate A (kg/L), suction filtration gets intermediate B then;

C, intermediate B add 8 times of amounts (kg/L), 50% ethanol and stir, and filter, and precipitation with the 95% alcohol immersion washing of 2 times of amount intermediate B (kg/L), is filtered again, is drying to obtain the baicalin elaboration.

Also be preferably:

A, baicalin crude product add 5 times of amounts (kg/L) water, and heating in water bath stirs, and add 40% sodium hydroxide solution adjusting pH value and are 6.0-7.0, the baicalin crude product is dissolved fully, filter, adding isopyknic ethanol in the filtrate is 1.0-2.5 with the hydrochloric acid adjust pH of 4mol/L immediately after stirring evenly, and is heated to 40 ℃, be incubated 40 minutes, room temperature was placed 20 hours, filtered, and precipitated with 1.5 times of baicalin crude products (kg/L), 40% washing with alcohol, suction filtration, drying get intermediate A then;

B, intermediate A add 5 times of amounts (kg/L) water, stir, add 30% sodium hydroxide solution adjusting pH value and be 6.0-7.0, make dissolving fully, filter, adding 4 times of volumes in the filtrate is the ethanol of 1.0-3.0 with the hydrochloric acid adjust pH, stir evenly, place 3h, filter, precipitation adds water, stir, adding isopyknic ethanol is 2.0-2.5 with the hydrochloric acid adjust pH of 2mol/L immediately after stirring evenly, and is heated to 85 ℃, insulation 30min, room temperature is placed 20h, filters, with the 40% washing with alcohol precipitation of 1.5 times of amount intermediate A (kg/L), filter, get intermediate B;

C, intermediate B add 5 times of amounts (kg/L), 40% ethanol and stir, and filter, and precipitation with the 90% alcohol immersion washing of 1.5 times of amount intermediate B (kg/L), is filtered again, is drying to obtain the baicalin elaboration.

Also be preferably:

A, baicalin crude product add 10 times of amounts (kg/L) water, and heating in water bath stirs, and add 30% sodium hydroxide solution adjusting pH value and are 6.0-7.0, the baicalin crude product is dissolved fully, filtering, is 1.0-2.5 with 2mol/L hydrochloric acid adjust pH immediately after the isopyknic ethanol of adding stirs evenly in the filtrate, is heated to 85 ℃, be incubated 20 minutes, room temperature was placed 10 hours, filtered, and precipitated with 3 times of baicalin crude products (kg/L), 60% washing with alcohol, suction filtration, drying get intermediate A then;

B, intermediate A add 8 times of amounts (kg/L) water, stir, it is 6.0-7.0 that the hydro-oxidation sodium solution is regulated the pH value, makes dissolving fully, filters, adding 8 times of volumes in the filtrate is the ethanol of 1.0-3.0 with the hydrochloric acid adjust pH, stir evenly, place 1h, filter, precipitation adds water, stir, adding isopyknic ethanol is 1.0-2.5 with the hydrochloric acid adjust pH immediately after stirring evenly, and is heated to 75 ℃, insulation 5min, room temperature is placed 10h, filters, with the 60% washing with alcohol precipitation of 3 times of amount intermediate A (kg/L), filtration, drying get intermediate B;

C, intermediate B add 10 times of amounts (kg/L), 60% ethanol and stir, and filter, and precipitation with the 99% alcohol immersion washing of 3 times of amount intermediate B (kg/L), is filtered again, is drying to obtain the baicalin elaboration.

After the inventive method adopts crude product with alkali dissolution, add alcohol and under acidic conditions, baicalin is precipitated out,, can remove neutral polar impurity with the alcohol washing; Use alkali dissolution once more, add the acidic ethanol precipitation, can remove scutellarin, the impurity that composition that chemical property such as wogonoside, polarity and baicalin are close and polarity are less; Add alcohol then and soak, the deacidification after drying, the discovery that the contriver is surprised, the baicalin elaboration content of baicalin that obtains like this can reach more than 99%, and the overall baicalin rate of transform is more than 85%.This method is made with extra care baicalin, and technology is simple, produces easily and realizes not having severe contamination, and content of baicalin is improved greatly, makes medicinal product such as injection liquid, and powder acanthin amount is more reliable, and is stable, and incidence rate of adverse reaction can significantly reduce.

Need content of baicalin is investigated in the process for purification of the present invention.The contriver adopts the method for Chinese Pharmacopoeia to measure, and method is as follows:

Instrument, reagent and medicine Waters2695-2996 type high performance liquid chromatograph, WatersSymmetry C18 (250mm * 4.6mm, 5 μ m), HS6150D, BENCHTOPCLEANERS type ultrasonic cleaner; METTLER TOLED AG135 type 100,000/electronic balance, methyl alcohol: chromatographically pure; U.S. Fisher; Water: purified water, phosphoric acid chromatographically pure; The emerging multiple fine chemistry industry institute in Tianjin.Baicalin reference substance (available from Chinese medicine bioassay institute, lot number is 110715-200815).

The chromatographic condition octadecylsilane chemically bonded silica is weighting agent chromatographic column (250mm * 4.6mm, 5 μ m).With methanol-water-phosphoric acid (47: 53: 0.2) is moving phase; Flow velocity is 1ml/min; Detect wavelength: 280nm; Number of theoretical plate calculates by the baicalin peak should be not less than 2500.

It is an amount of that the preparation precision of reference substance solution takes by weighing the baicalin reference substance, adds the solution that methyl alcohol is made 60 μ g/ml, shakes up, promptly.

The preparation of need testing solution: get the about 15mg of baicalin sample, the accurate title, decide, and puts in the 250ml volumetric flask, adds methyl alcohol 200ml, ultrasonic 15min, and cooling, fixed molten to scale, with millipore filtration (0.45 μ m) filtration, get subsequent filtrate, promptly.

Accurate reference substance solution and each the 10 μ l of need testing solution of drawing of assay method inject liquid chromatograph, with the peak area external standard method, promptly.

Embodiment

Following embodiment is used to illustrate process for purification of the present invention, but it can not constitute any restriction to scope of the present invention.

Embodiment 1:

A, baicalin crude product 0.3Kg, add the deionized water of 2.5L, heating in water bath stirs into homogeneous body, under agitation transfers the pH6.44 dissolving with 30% sodium hydroxide solution, filter, immediately with the HCL accent pH2.08 of 2mol/L, be heated to 50 ℃ of insulation 40min under stirring, room temperature placement 12h after 95% medicinal alcohol of adding 2.5L stirs evenly in the filtrate, filter, the medicinal alcohol placement natural subsidence that adds 600ml50% again on filter cake does not arrive drips, and suction filtration, drying get intermediate A then;

B, intermediate A add the 1.5L deionized water, stir into homogeneous body, transfer the pH6.80 dissolving with 30% sodium hydroxide solution, filtration, and adding 9.1L transfers 95% medicinal alcohol of pH2.20 to stir evenly the back with hydrochloric acid and places 3h, filtration in the filtrate.Precipitation adds the 1.0L deionized water, stir into homogeneous body, after 95% medicinal alcohol that adds 1.0L again stirs evenly immediately the HCL with 2mol/L transfer pH2.10, be heated to 84 ℃ of backflow 5min, room temperature is placed 14h, filters, and the medicinal alcohol placement natural subsidence that adds 600ml 50% again on filter cake does not arrive drips, suction filtration gets intermediate B then;

The medicinal alcohol that c, intermediate B add 2.0L 50% stirs, and filters, and the ethanol that adds 600ml 95% again on filter cake is placed 1h, suction filtration will be deposited in 60 ℃ of following drying under reduced pressure then, get baicalin elaboration 158.9g, the gained sample is detected with high performance liquid phase, and its content is 99.76%.

Embodiment 2:

A, baicalin crude product 0.3Kg, add the deionized water of 2.0L, heating in water bath stirs into homogeneous body, under agitation transfers the pH6.80 dissolving with 20% sodium hydroxide solution, filter, immediately with the HCL accent PH2.05 of 4mol/L, be heated to 75 ℃ of insulation 30min under stirring, room temperature placement 16h after 95% medicinal alcohol of adding 2.2L stirs evenly in the filtrate, filter, the medicinal alcohol placement natural subsidence that adds 600ml50% again on filter cake does not arrive drips, and suction filtration, drying get intermediate A then;

B, intermediate A add the 1.8L deionized water, stir into homogeneous body, transfer the PH6.80 dissolving with 40% sodium hydroxide solution, filter, and add in the filtrate to transfer pH5.3 with hydrochloric acid immediately after 8L 95% medicinal alcohol stirs evenly, and place 2h then, filter.Precipitation adds the 1.0L deionized water, stir into homogeneous body, after stirring evenly, 95% medicinal alcohol that adds 1.0L again transfers pH2.50 with 2NHCL immediately, be heated to 84 ℃ of backflow 5min, room temperature is placed 13h, filters, and the medicinal alcohol placement natural subsidence that adds 400ml50% again on filter cake does not arrive drips, suction filtration gets intermediate B then;

The medicinal alcohol that c, intermediate B add 2.0L 50% stirs, and filters, and the ethanol that adds 400ml 95% again on filter cake is placed 1h, suction filtration will be deposited in 60 ℃ of following drying under reduced pressure then, get 160.23g, the gained sample is detected with high performance liquid phase, and its content is 99.51%.

Embodiment 3:

A, baicalin crude product 0.3Kg add the deionized water of 2.0L, heating in water bath stirs into homogeneous body, under agitation transfer the pH7.0 dissolving, filter, transfer PH2.08 with 2NHCL immediately after 95% medicinal alcohol of adding 2.0L stirs evenly in the filtrate with 20% sodium hydroxide solution, be heated to 78 ℃ of insulation 30min under stirring, room temperature is placed 12h, filters, and the medicinal alcohol placement natural subsidence that adds 400ml50% again on filter cake does not arrive drips, suction filtration, drying get intermediate A then;

B, intermediate A add the 1.5L deionized water, stir into homogeneous body, transfer the pH6.50 dissolving with 40% sodium hydroxide solution, filter, and add in the filtrate to transfer pH4.9 with hydrochloric acid immediately after 11.0L 95% medicinal alcohol stirs evenly, and place 1h then, filter.Precipitation adds the 0.8L deionized water, stir into homogeneous body, after 95% medicinal alcohol that adds 0.8L again stirs evenly immediately the HCL with 2mol/L transfer pH2.20, be heated to 84 ℃ of backflow 5min, room temperature is placed 12h, filters, and the medicinal alcohol placement natural subsidence that adds 400ml50% again on filter cake does not arrive drips, filter then, get intermediate B;

The medicinal alcohol that c, intermediate B add 2.0L 50% stirs, and filters, and the ethanol that adds 400ml 95% again on filter cake is placed 1h, suction filtration will be deposited in 60 ℃ of following drying under reduced pressure then, get 164.49g, the gained sample is detected with high performance liquid phase, and its content is 99.01%.

Embodiment 4:

A, baicalin crude product 0.3Kg add the deionized water of 2.0L, heating in water bath stirs into homogeneous body, under agitation transfer the pH6.54 dissolving, filter, transfer pH2.16 with 4NHCL immediately after 95% medicinal alcohol of adding 2.0L stirs evenly in the filtrate with 30% sodium hydroxide solution, be heated to 71 ℃ of insulation 30min under stirring, room temperature is placed 16h, filters, and the medicinal alcohol placement natural subsidence that adds 500ml50% again on filter cake does not arrive drips, suction filtration, drying get intermediate A then;

B, intermediate A add the 1.5L deionized water, stir into homogeneous body, transfer the pH6.50 dissolving with 40% sodium hydroxide solution, filter, and add in the filtrate to transfer pH4.9 with hydrochloric acid immediately after 11.0L 95% medicinal alcohol stirs evenly, and place 1h then, filter.Precipitation adds the 0.8L deionized water, stir into homogeneous body, after 95% medicinal alcohol that adds 0.8L again stirs evenly immediately the HCL with 2mol/L transfer pH2.20, be heated to 84 ℃ of backflow 5min, room temperature is placed 12h, filters, and the medicinal alcohol placement natural subsidence that adds 400ml50% again on filter cake does not arrive drips, filter then, get intermediate B;

The medicinal alcohol that c, intermediate B add 2.0L 50% stirs, and filters, and the ethanol that adds 400ml 95% again on filter cake is placed 1h, suction filtration will be deposited in 60 ℃ of following drying under reduced pressure then, get 152.6g, the gained sample is detected with high performance liquid phase, and its content is 99.31%.

Embodiment 5:

A, baicalin crude product 0.3Kg add the deionized water of 2.0L, heating in water bath stirs into homogeneous body, under agitation transfer the pH6.72 dissolving, filter, use the HCL of 2mol/L to transfer pH2.09 immediately after 95% medicinal alcohol of adding 2.0L stirs evenly in the filtrate with 20% sodium hydroxide solution, be heated to 80 ℃ of insulation 30min under stirring, room temperature is placed 12h, filters, and the medicinal alcohol placement natural subsidence that adds 400ml50% again on filter cake does not arrive drips, suction filtration, drying get intermediate A then;

B, intermediate A add the 1.3L deionized water, stir into homogeneous body, transfer the pH6.80 dissolving with 40% sodium hydroxide solution, filtration, and adding 9.1L transfers 95% medicinal alcohol of pH1.9 to stir evenly the back with hydrochloric acid and places 3h, filtration in the filtrate.Precipitation adds the 0.8L deionized water, stir into homogeneous body, after 95% medicinal alcohol that adds 0.8L again stirs evenly immediately the HCL with 2mol/L transfer pH2.10, be heated to 84 ℃ of backflow 5min, room temperature is placed 14h, filters, and the medicinal alcohol placement natural subsidence that adds 400ml50% again on filter cake does not arrive drips, suction filtration gets intermediate B then;

The medicinal alcohol that c, intermediate B add 1.6L 50% stirs, and filters, and the ethanol that adds 400ml 95% again on filter cake is placed 1h, suction filtration will be deposited in 60 ℃ of following drying under reduced pressure then, get 163.60g, the gained sample is detected with high performance liquid phase, and its content is 99.17%.

Embodiment 6:

A, baicalin crude product 0.3Kg add the deionized water of 2.0L, heating in water bath stirs into homogeneous body, under agitation transfer the pH6.74 dissolving, filter, use the HCL of 2mol/L to transfer pH2.11 immediately after 95% medicinal alcohol of adding 2.0L stirs evenly in the filtrate with 20% sodium hydroxide solution, be heated to 81 ℃ of insulation 28min under stirring, room temperature is placed 12h, filters, and the medicinal alcohol placement natural subsidence that adds 400ml50% again on filter cake does not arrive drips, suction filtration, drying get intermediate A then;

B, intermediate A add the 2.0L deionized water, stir into homogeneous body, transfer the pH6.80 dissolving with 40% sodium hydroxide solution, filtration, and adding 10L transfers 95% medicinal alcohol of pH1.6 to stir evenly the back with hydrochloric acid and places 3h, filtration in the filtrate.Precipitation adds the 0.8L deionized water, stir into homogeneous body, after 95% medicinal alcohol that adds 0.8L again stirs evenly immediately the HCL with 2mol/L transfer pH2.30, be heated to 70 ℃ of insulation 20min, room temperature is placed 14h, filters, and the medicinal alcohol placement natural subsidence that adds 400ml50% again on filter cake does not arrive drips, suction filtration gets intermediate B then;

The medicinal alcohol that c, intermediate B add 1.6L 50% stirs, and filters, and the ethanol that adds 400ml 95% again on filter cake is placed 1h, suction filtration will be deposited in 60 ℃ of following drying under reduced pressure then, get 164.60g, the gained sample is detected with high performance liquid phase, and its content is 99.29%.

Embodiment 7:

A, baicalin crude product 0.3Kg add the deionized water of 2.0L, heating in water bath stirs into homogeneous body, under agitation transfer the pH6.72 dissolving, filter, use the HCL of 2mol/L to transfer pH2.09 immediately after 95% medicinal alcohol of adding 2.0L stirs evenly in the filtrate with 20% sodium hydroxide solution, be heated to 80 ℃ of insulation 25min under stirring, room temperature is placed 12h, filters, and the medicinal alcohol placement natural subsidence that adds 400ml50% again on filter cake does not arrive drips, suction filtration, drying get intermediate A then;

B, intermediate A add the 1.6L deionized water, stir into homogeneous body, transfer the pH6.89 dissolving with 40% sodium hydroxide solution, filtration, and adding 9.0L transfers 95% medicinal alcohol of pH2.2 to stir evenly the back with hydrochloric acid and places 3h, filtration in the filtrate.Precipitation adds the 0.8L deionized water, stir into homogeneous body, after 95% medicinal alcohol that adds 0.8L again stirs evenly immediately the HCL with 2mol/L transfer pH2.10, be heated to 60 ℃ and place 30min, room temperature is placed 14h then, filters, and the medicinal alcohol placement natural subsidence that adds 600ml50% again on filter cake does not arrive drips, suction filtration gets intermediate B then;

The medicinal alcohol that c, intermediate B add 1.6L 50% stirs, and filters, and the ethanol that adds 400ml 95% again on filter cake is placed 1h, suction filtration will be deposited in 60 ℃ of following drying under reduced pressure then, get 163.60g, the gained sample is detected with high performance liquid phase, and its content is 99.51%.

Embodiment 8:

A, baicalin crude product 0.3Kg add the deionized water of 2.0L, heating in water bath stirs into homogeneous body, under agitation transfer the pH6.69 dissolving, filter, use the HCL of 2mol/L to transfer pH2.09 immediately after 95% medicinal alcohol of adding 2.0L stirs evenly in the filtrate with 20% sodium hydroxide solution, be heated to 43 ℃ of insulation 40min under stirring, room temperature is placed 19h, filters, and the medicinal alcohol placement natural subsidence that adds 400ml50% again on filter cake does not arrive drips, suction filtration, drying get intermediate A then;

B, intermediate A add the 1.4L deionized water, stir into homogeneous body, transfer the pH6.80 dissolving with 40% sodium hydroxide solution, filter, give to add in the filtrate and place 3h after 10L transfers 95% medicinal alcohol of pH1.95 to stir evenly with hydrochloric acid, filter, precipitation adds the 1.0L deionized water, stirs into homogeneous body, after 95% medicinal alcohol that adds 1.0L again stirs evenly immediately the HCL with 2mol/L transfer pH2.10, be heated to 70 ℃ of insulation 30min, room temperature is placed 14h, filters, and the medicinal alcohol placement natural subsidence that adds 400ml50% again on filter cake does not arrive drips, suction filtration gets intermediate B then;

The medicinal alcohol that c, intermediate B add 1.6L50% stirs, and filters, and the ethanol that adds 400ml 95% again on filter cake is placed 1h, suction filtration will be deposited in 60 ℃ of following drying under reduced pressure then, get 154.69g, the gained sample is detected with high performance liquid phase, and its content is 99.07%.

Claims (5)

1. the process for purification of a baicalin is characterized in that this baicalin process for purification may further comprise the steps:

A, baicalin crude product add water, heating in water bath stirs, and it is 6.0-7.0 that the hydro-oxidation sodium solution is regulated the pH value, and the baicalin crude product is dissolved fully, filter, after adding ethanol stirs evenly in the filtrate is 1.0-2.5 with the hydrochloric acid adjust pH immediately, heat tracing, and room temperature is placed, filter, with 40-60% washing with alcohol precipitation, filtration, drying get intermediate A then;

B, intermediate A add water, stir, and it is 6.0-7.0 that the hydro-oxidation sodium solution is regulated the pH value, make dissolving fully, filter, adding with the hydrochloric acid adjust pH in the filtrate is the ethanol of 1.0-3.0, stir evenly, or transfer PH4.0-6.0 with HCL immediately after adding ethanol, place, filter, precipitation adds water, stirs, after adding ethanol stirs evenly is pH1.0-2.5 with the hydrochloric acid tone pitch immediately, heat tracing, and room temperature is placed, filter, with 40-60% washing with alcohol precipitation, filter, get intermediate B then;

C, intermediate B add 40-60% ethanol and stir, and filter, and precipitation with the alcohol immersion washing, is filtered again, is drying to obtain the baicalin elaboration.

2. process for purification according to claim 1 is characterized in that described baicalin process for purification may further comprise the steps:

A, baicalin crude product add 5-15 and doubly measure (kg/L) water, heating in water bath stirs, add 10-40% sodium hydroxide solution adjusting pH value and be 6.0-7.0, the baicalin crude product is dissolved fully, filter, adding isopyknic ethanol in the filtrate is 1.0-2.5 with the hydrochloric acid adjust pH of 2-4mol/L immediately after stirring evenly, be heated to 40-85 ℃, be incubated 20-40 minute, room temperature was placed 10-20 hour, filtered, and precipitated with 1-5 times of baicalin crude product (kg/L) 40-60% washing with alcohol, suction filtration, drying get intermediate A then;

B, intermediate A adds 5-8 and doubly measures (kg/L) water, stir, it is 6.0-7.0 that the hydro-oxidation sodium solution is regulated the pH value, makes dissolving fully, filter, adding 4-8 times of volume in the filtrate is the ethanol of 1.0-3.0 with the hydrochloric acid adjust pH, stirs evenly, or transfers pH4.0-6.0 with HCL immediately after adding ethanol, place 1-3h, filter, precipitation adds water, stirs, adding isopyknic ethanol is 1.0-2.5 with the hydrochloric acid adjust pH immediately after stirring evenly, be heated to 40-85 ℃, insulation 5-30min, room temperature is placed 10-20h, filter, the 40-60% washing with alcohol of doubly measuring intermediate A (kg/L) with 1-5 precipitates, and filters, drying gets intermediate B;

C, intermediate B add 5-10 doubly to be measured (kg/L) 40-60% ethanol and stirs, and filters, and precipitation is doubly measured the 90-99% alcohol immersion washing of intermediate B (kg/L) again with 1-5, filter, and is drying to obtain the baicalin elaboration.

3. process for purification according to claim 2 is characterized in that described baicalin process for purification may further comprise the steps:

A, baicalin crude product add 8 times of amounts (kg/L) water, and heating in water bath stirs, and add 20% sodium hydroxide solution adjusting pH value and are 6.0-7.0, the baicalin crude product is dissolved fully, filter, adding isopyknic ethanol in the filtrate is 1.0-2.5 with the hydrochloric acid adjust pH of 2mol/L immediately after stirring evenly, and is heated to 50 ℃, be incubated 40 minutes, room temperature was placed 12 hours, filtered, and precipitated with 2 times of baicalin crude products (kg/L) 40-60% washing with alcohol, suction filtration, drying get intermediate A then;

B, intermediate A adds 6 times of amounts (kg/L) water, stir, it is 6.0-7.0 that the hydro-oxidation sodium solution is regulated the pH value, makes dissolving fully, filters, adding 4 times of volumes in the filtrate is the ethanol of 1.0-3.0 with the hydrochloric acid adjust pH, stir evenly, place 3h, filter, precipitation adds the water of 4 times of amount intermediate A (kg/L), stir, adding isopyknic 95% ethanol is 1.0-2.5 with 2mol/L hydrochloric acid adjust pH immediately after stirring evenly, and is heated to 40-85 ℃, heat tracing 5-30min, room temperature is placed 10-20h, filters, with the 50% washing with alcohol precipitation of 2 times of amount intermediate A (kg/L), suction filtration gets intermediate B then;

C, intermediate B add 8 times of amounts (kg/L), 50% ethanol and stir, and filter, and precipitation with the 95% alcohol immersion washing of 2 times of amount intermediate B (kg/L), is filtered again, is drying to obtain the baicalin elaboration.

4. process for purification according to claim 2 is characterized in that described baicalin process for purification may further comprise the steps:

A, baicalin crude product add 5 times of amounts (kg/L) water, and heating in water bath stirs, and add 40% sodium hydroxide solution adjusting pH value and are 6.0-7.0, the baicalin crude product is dissolved fully, filter, adding isopyknic ethanol in the filtrate is 1.0-2.5 with the hydrochloric acid adjust pH of 4mol/L immediately after stirring evenly, and is heated to 40 ℃, be incubated 40 minutes, room temperature was placed 20 hours, filtered, and precipitated with 1.5 times of baicalin crude products (kg/L), 40% washing with alcohol, suction filtration, drying get intermediate A then;

B, intermediate A add 5 times of amounts (kg/L) water, stir, add 30% sodium hydroxide solution adjusting pH value and be 6.0-7.0, make dissolving fully, filter, adding 4 times of volumes in the filtrate is the ethanol of 1.0-3.0 with the hydrochloric acid adjust pH, stir evenly, place 3h, filter, precipitation adds water, stir, adding isopyknic ethanol is 2.0-2.5 with the hydrochloric acid adjust pH of 2mol/L immediately after stirring evenly, and is heated to 85 ℃, insulation 30min, room temperature is placed 20h, filters, with the 40% washing with alcohol precipitation of 1.5 times of amount intermediate A (kg/L), filter, get intermediate B;

C, intermediate B add 5 times of amounts (kg/L), 40% ethanol and stir, and filter, and precipitation with the 90% alcohol immersion washing of 1.5 times of amount intermediate B (kg/L), is filtered again, is drying to obtain the baicalin elaboration.

5. process for purification according to claim 2 is characterized in that described baicalin process for purification may further comprise the steps:

A, baicalin crude product add 10 times of amounts (kg/L) water, and heating in water bath stirs, and add 30% sodium hydroxide solution adjusting pH value and are 6.0-7.0, the baicalin crude product is dissolved fully, filtering, is 1.0-2.5 with 2mol/L hydrochloric acid adjust pH immediately after the isopyknic ethanol of adding stirs evenly in the filtrate, is heated to 85 ℃, be incubated 20 minutes, room temperature was placed 10 hours, filtered, and precipitated with 3 times of baicalin crude products (kg/L), 60% washing with alcohol, suction filtration, drying get intermediate A then;

B, intermediate A add 8 times of amounts (kg/L) water, stir, it is 6.0-7.0 that the hydro-oxidation sodium solution is regulated the pH value, makes dissolving fully, filters, adding 8 times of volumes in the filtrate is the ethanol of 1.0-3.0 with the hydrochloric acid adjust pH, stir evenly, place 1h, filter, precipitation adds water, stir, adding isopyknic ethanol is 1.0-2.5 with the hydrochloric acid adjust pH immediately after stirring evenly, and is heated to 75 ℃, insulation 5min, room temperature is placed 10h, filters, with the 60% washing with alcohol precipitation of 3 times of amount intermediate A (kg/L), filtration, drying get intermediate B;

C, intermediate B add 10 times of amounts (kg/L), 60% ethanol and stir, and filter, and precipitation with the 99% alcohol immersion washing of 3 times of amount intermediate B (kg/L), is filtered again, is drying to obtain the baicalin elaboration.