CN1500798A - Preparing method for kutkin II crystal - Google Patents
Preparing method for kutkin II crystal Download PDFInfo
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- CN1500798A CN1500798A CNA021493561A CN02149356A CN1500798A CN 1500798 A CN1500798 A CN 1500798A CN A021493561 A CNA021493561 A CN A021493561A CN 02149356 A CN02149356 A CN 02149356A CN 1500798 A CN1500798 A CN 1500798A
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- rhizoma picrorhizae
- acid
- glucoside
- wash
- picrorhizae glucoside
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Abstract
The present invention relates to the extraction, separation and purification process of natural compound picroside II with medicinal use. The present invention provides the process including extraction of picroside II from the root and stem of picrorhiza scrophulariiflora Pennell and picrorhiza kurroa Royle excellent enth; separation via adsorption, alkali solution washing and re-adsorption; and purification crystallization and re-crystallization in the composite solvent of ethyl acetate and absolute alcohol.
Description
Rhizoma Picrorhizae glucoside II (Picroside II is a kind of iridoid glycoside analog derivative Amphicoside), have protect the liver, physiologically active (medicinal use patent applied for, application number 02125544.X) such as anti-inflammatory, antianaphylaxis, anti-asthma.S.K.Kapoor in 1971 etc. separate from plant Amphicome emodi Lindl first and obtain Rhizoma Picrorhizae glucoside II, separate obtaining Rhizoma Picrorhizae glucoside II later in succession from India's Rhizoma Picrorhizae (picrorhiza kurroaRoyle ex Benth) rhizome and Tibet picrorhiza rhizome (picrorhiza scrophulariifloraPennell) rhizome.Used method is that the plumbic acetate precipitator method, silica gel column chromatography and reverse silica gel column chromatography separate, but does not all obtain Rhizoma Picrorhizae glucoside II crystallization product.
The chemical structural formula of Rhizoma Picrorhizae glucoside II is as follows:
Molecular formula: C
23H
28O
13
Molecular weight: 512.1530
Fusing point: 214-215 ℃
Solvability: water, methyl alcohol, ethanol are easily molten, acetone solution, and ethyl acetate is molten slightly.
The invention provides the preparation method of Rhizoma Picrorhizae glucoside II with industrial value.Its separation method and crystallization method are quick, and be simple, practicality.Compare with technology in the past, the method novelty has tangible novelty.
The invention provides the extraction of Rhizoma Picrorhizae glucoside II, separate, the method of purifying is, get Tibet picrorhiza rhizome (picrorhiza scrophulariiflora Pennell) and India's Rhizoma Picrorhizae (picrorhizakurroa Royle ex Benth) rhizome or its pulverizing product, water, methyl alcohol, ethanol, acetone equal solvent or its two kinds, multiple mixed solvent extracts, extracting solution vacuum concentration below 70 ℃ is to doing (or organic solvent-free), add water to suitable volume, remove precipitation (if any precipitation), the adsorption column A that last conventional processing is good, wash decon with water, to closely colourless, and sugared reaction test should be negative (molish reaction negative), again with buck or contain lower concentration methyl alcohol, ethanol, the buck wash-out Rhizoma Picrorhizae glucoside II of acetone, elutriant is immediately with the acid neutralization, neutralizer is gone up the good adsorption column B of conventional processing once more, wash with water to closely colourless, use the pure water desalination, use methyl alcohol at last, ethanol, acetone and other organic solvent or their water-containing solvent wash-out, elutriant is concentrated into dried, residue ethanol, the mixed solution of the organic solvent that the acetone isopolarity is bigger or they and ethyl acetate extracts, extracting solution vacuum concentration below 70 ℃ is to doing, get the Rhizoma Picrorhizae glucoside II crude product, with ethyl acetate-dehydrated alcohol mixed solvent crystallization and recrystallization, promptly get Rhizoma Picrorhizae glucoside II.
1, above-mentioned to extract the used solvent of composition contain Rhizoma Picrorhizae glucoside II from crude drug can be water, ethanol, methyl alcohol, acetone, both can use separately, also can two or more solvent merges to use.
2, above-mentionedly extract the composition contain Rhizoma Picrorhizae glucoside II from crude drug and can use refluxing extraction, also can extract with the diacolation extraction or with apparatus,Soxhlet's.
3, the used filler of above-mentioned filling adsorption column can be the resin of nonpolar or low-pole, for example, and styrene type (comprising vinyl toluene type, ethyl styrene type) or vinyl cyanide type interpolymer resin.It also can be activated carbon.
4, above-mentioned can be the aqueous solution of sodium hydroxide, potassium hydroxide, ammonia from the used buck of adsorption column A wash-out Rhizoma Picrorhizae glucoside II, and these aqueous solution can be to contain concentration to be not more than 20% methyl alcohol, ethanol and acetone.
5, the used acid of above-mentioned neutralization bases elutriant can be organic acid, as formic acid, acetate, propionic acid etc.Also can be the mineral acid and their aqueous solution, example hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid etc.
6, if the alkali lye that wash-out is used in above-mentioned 4 is when containing methyl alcohol, ethanol, acetone and other organic solvent, must thin up after the neutralization makes it contain the alcohol amount and is not more than 10%, goes up the macroporous resin column enrichment again, and wash the decolouring desalination with water.
7, above-mentioned can be methyl alcohol, ethanol, acetone, ethyl acetate or their mixture from the used solvent of adsorption column B wash-out Rhizoma Picrorhizae glucoside II, or the mixture of they and water.
8, extracting the used solvent of Rhizoma Picrorhizae glucoside II from above-mentioned residue can be methyl alcohol, dehydrated alcohol, acetone or mixed solution, or the mixed solution of they and ethyl acetate.
Embodiment
With following embodiment the present invention is specified, but the present invention is not limited to down
The content that row embodiment comprises.
[embodiment one]
Get the meal 500g of Tibet picrorhiza rhizome (picrorhiza scrophulariiflora Pennell) rhizome, use 50% ethanol percolate extraction, get percolate 5000ml, be evaporated to about 400ml and remove residual ethanol, the water that adds equivalent, on the D101 type macroporous resin column A (3kgD101 type macroporous resin places in the glass column of Φ=10cm) that handled well, the conventional flush away impurity of water, to closely colourless, and sugared reaction test be negative (molish reaction negative), with the sodium hydroxide solution 5000ml wash-out Rhizoma Picrorhizae glucoside II that contains 15% alcoholic acid 2%, elutriant is neutralized to pH value 6 with acetate immediately, neutralizer adds the ordinary water of equivalent, on the D101 type macroporous resin column B (2kgD101 type macroporous resin places in the glass column of Φ=8cm) that handled well, wash with water to closely colourless, use the pure water desalination, with 85% ethanol 3000ml wash-out, elutriant is concentrated into dried, (V/V=3: 2) mixed-liquor return extracts three (500ml to residue with ethyl acetate-dehydrated alcohol, 400ml, 400ml), extracting solution is extremely placed crystallization behind about 300ml in vacuum concentration below 70 ℃, with promptly getting Rhizoma Picrorhizae glucoside II 21.7g behind ethyl acetate-dehydrated alcohol (3V/V=:2) recrystallization.
[embodiment two]
Get the meal 500g of Tibet picrorhiza rhizome (picrorhiza scrophulariiflora Pennell) rhizome, use 50% ethanol percolate extraction, get percolate 5000ml, be evaporated to about 400ml and remove residual ethanol, the water that adds equivalent, on the macroporous resin column A (3kgD101 type macroporous resin places in the glass column of Φ=10cm) that handled well, the conventional flush away impurity of water, to closely colourless, and sugared reaction test feminine gender (molish reaction negative), with the sodium hydroxide solution 5000ml wash-out Rhizoma Picrorhizae glucoside II that contains 2%, elutriant is neutralized to pH value 6.5 with acetate immediately, (the 3kg gac places in the glass column of Φ=10cm the activated carbon column B that has handled well on the neutralizer, before the dress post, used gac was 140 ℃ of bakings 4.5 hours), wash with water to nearly colourless and potential of hydrogen when neutral, with using 75% ethanol 3000ml wash-out after the pure water desalination again, elutriant is concentrated into dried, (V/V=3: 1) mixed-liquor return extracts three (500ml to residue with ethyl acetate-dehydrated alcohol, 400ml, 400ml), extracting solution is concentrated into about 300ml and places crystallization, with ethyl acetate-dehydrated alcohol (V/V=3: 1) promptly get Rhizoma Picrorhizae glucoside II 17.5g behind the recrystallization.
[embodiment three]
Get Tibet picrorhiza rhizome (picrorhiza scrophulariiflora Pennell) rhizome 500g, be added in the 4000ml80 ℃ of water, constantly stirring down, slow fire is heated to the maintenance 10 minutes of boiling, the leaching decoction liquor, the dregs of a decoction add water 3000ml and decoct boiling 20 minutes, the leaching decoction liquor, the dregs of a decoction add water 3000ml and decoct boiling 30 minutes, the leaching decoction liquor, the decoction liquor that merges all leachings, on the D101 type macroporous resin column A (3kgD101 type macroporous resin places in the glass column of Φ=10cm) that handled well, the conventional flush away impurity of water, to closely colourless, and sugared reaction test be negative (molish reaction negative), with the sodium hydroxide solution 5000ml wash-out Rhizoma Picrorhizae glucoside II that contains 2%, elutriant is neutralized to pH value 7 with acetate immediately, the D101 type macroporous resin column B that has handled well on the neutralizer (2kgD101 type macroporous resin column places in the glass column of Φ=8cm), wash with water to nearly colourless and potential of hydrogen when neutral, use the pure water desalination, with 65% ethanol 3000ml wash-out, elutriant is concentrated into dried, (V/V=65: 35) mixed-liquor return extracts three (500ml to residue with ethyl acetate-dehydrated alcohol, 400ml, 400ml), extracting solution is concentrated into about 300ml for 70 ℃ and places crystallization, with ethyl acetate-dehydrated alcohol (V/V=65: 35) promptly get Rhizoma Picrorhizae glucoside II 22.6g behind the recrystallization.
[embodiment four]
Get the meal 500g of Tibet picrorhiza rhizome (picrorhiza scrophulariiflora Pennell) rhizome, use 50% ethanol percolate extraction, get percolate 5000ml, be evaporated to about 400ml and remove residual ethanol, the water that adds equivalent, on the activated carbon column A that handled well (the 3kg gac places in the glass column of Φ=12cm, before the dress post, used gac was 140 ℃ of bakings 4.5 hours), the conventional flush away impurity of water, to closely colourless, and sugared reaction test be negative (molish reaction negative), with the sodium hydroxide solution 5000ml wash-out Rhizoma Picrorhizae glucoside II that contains 10% alcoholic acid 2%, elutriant is neutralized to pH value 7 with acetate immediately, neutralizer adds the ordinary water of equivalent, on the macroporous resin column B (2kgD101 type macroporous resin places in the glass column of Φ=8cm) that handled well, wash with water to nearly colourless and potential of hydrogen when neutral, use the pure water desalination, use 45% ethanol, 3000 wash-outs again, elutriant is concentrated into dried, (V/V=1: 1) mixed-liquor return extracts three (500ml to residue with ethyl acetate-dehydrated alcohol, 400ml, 400ml), extracting solution is concentrated into about 300ml and places crystallization, with ethyl acetate-dehydrated alcohol (V/V=1: 1) promptly get Rhizoma Picrorhizae glucoside II 19.6g behind the 300ml recrystallization.
[embodiment five]
Get the meal 500g of India's Rhizoma Picrorhizae (picrorhiza kurroa Royle ex Benth) rhizome, use 50% ethanol percolate extraction, get percolate 5000ml, be evaporated to about 400ml and remove residual ethanol, the water that adds equivalent, on the activated carbon column A that handled well (the 3kg gac places in the glass column of Φ=12cm, before the dress post, used gac was 140 ℃ of bakings 4.5 hours), the conventional flush away impurity of water, to closely colourless, and sugared reaction test be negative (molish reaction negative), with the sodium hydroxide solution 5000ml wash-out Rhizoma Picrorhizae glucoside II that contains 10% alcoholic acid 2%, elutriant is neutralized to pH value 7 with acetate immediately, neutralizer adds the ordinary water of equivalent, on the macroporous resin column B (2kgD101 type macroporous resin places in the glass column of Φ=8cm) that handled well, wash with water to nearly colourless and potential of hydrogen when neutral, use the pure water desalination, with 45% ethanol, 3000 wash-outs, elutriant concentrate as for, (V/V=1: 1) mixed-liquor return extracts three (500ml to residue with ethyl acetate-dehydrated alcohol, 400ml, 400ml), extracting solution is concentrated into about 300ml and places crystallization, with ethyl acetate-dehydrated alcohol (V/V=1: 1) promptly get Rhizoma Picrorhizae glucoside II 9.6g behind the 300ml recrystallization.
[embodiment six]
Get the meal 500g of India's Rhizoma Picrorhizae (picrorhiza kurroa Royle ex Benth) rhizome, use 50% ethanol percolate extraction, get percolate 5000ml, be evaporated to about 400ml and remove residual ethanol, the water that adds equivalent, on the activated carbon column A that handled well (the 3kg gac places in the glass column of Φ=12cm, before the dress post, used gac was 140 ℃ of bakings 4.5 hours), the conventional flush away impurity of water, to closely colourless, and sugared reaction test is negative (molish reaction negative), and with the sodium hydroxide solution 5000ml wash-out Rhizoma Picrorhizae glucoside II that contains 10% alcoholic acid 2%, elutriant is neutralized to pH value 7 with acetate immediately, neutralizer adds the ordinary water of equivalent, on the macroporous resin column B (2kgDM that handled well
2The type macroporous resin places in the glass column of Φ=8cm), wash with water to nearly colourless and potential of hydrogen when neutral, use the pure water desalination, with 45% ethanol, 3000 wash-outs, elutriant is concentrated into dried, and (V/V=1: 1) mixed-liquor return extracts three (500ml to residue with ethyl acetate-dehydrated alcohol, 400ml, 400ml), extracting solution is concentrated into about 300ml and places crystallization, with ethyl acetate-dehydrated alcohol (V/V=1: 1) promptly get Rhizoma Picrorhizae glucoside II 9.0g behind the 300ml recrystallization.
[embodiment seven]
Get Tibet picrorhiza rhizome (picrorhiza scrophulariiflora Pennell) rhizome 500g, be added in the 4000ml80 ℃ of water, constantly stirring down, slow fire is heated to the maintenance 10 minutes of boiling, the leaching decoction liquor, the dregs of a decoction add water 3000ml and decoct boiling 20 minutes, the leaching decoction liquor, the dregs of a decoction add water 3000ml and decoct boiling 30 minutes, the leaching decoction liquor, the decoction liquor that merges all leachings, on the activated carbon column A that handled well (the 3kg gac places in the glass column of Φ=12cm, before the dress post, used gac was 140 ℃ of bakings 4.5 hours), the conventional flush away impurity of water, to closely colourless, and sugared reaction test is negative (molish reaction negative), and with the sodium hydroxide solution 5000ml wash-out Rhizoma Picrorhizae glucoside II that contains 10% alcoholic acid 2%, elutriant is neutralized to pH value 7 with acetate immediately, neutralizer adds the ordinary water of equivalent, on the macroporous resin column B (2kgD that handled well
2The type macroporous resin places in the glass column of Φ=8cm), wash with water to nearly colourless and potential of hydrogen when neutral, use the pure water desalination, use 45% ethanol, 3000 wash-outs again, elutriant is concentrated into dried, and (V/V=1: 1) mixed-liquor return extracts three (500ml to residue with ethyl acetate-dehydrated alcohol, 400ml, 400ml), extracting solution is concentrated into about 300ml and places crystallization, with ethyl acetate-dehydrated alcohol (V/V=1: 1) promptly get Rhizoma Picrorhizae glucoside II 19.6g behind the 300ml recrystallization.
Claims (7)
1, a kind ofly be used for Tibet picrorhiza rhizome (picrorhiza scrophulariiflora Pennell) and India's Rhizoma Picrorhizae (picrorhiza kurroa Royle ex Benth) rhizome prepares the method for Rhizoma Picrorhizae glucoside II, it is characterized in that, Tibet picrorhiza rhizome (or India's Rhizoma Picrorhizae) is through water, methyl alcohol, ethanol, acetone or its mixed solvent extract, compositions such as Rhizoma Picrorhizae glucoside II after extracting solution concentrates in the aqueous solution of the extract of gained are after adsorbents adsorb is handled, separate Rhizoma Picrorhizae glucoside II with the basic solution wash-out, alkaline eluant neutralizes with acid, but basic solvent wash-out compositions such as the Rhizoma Picrorhizae glucoside II in the neutralizer are once more after handling with adsorbents adsorb, use methyl alcohol, ethanol, acetone or its mixed solvent, the perhaps mixed solvent wash-out of they and water, after elutriant is concentrated into and does, residue anhydrous solvent such as methyl alcohol, ethanol, acetone, ethyl acetate extraction, extracting solution is concentrated into dried, promptly get the Rhizoma Picrorhizae glucoside II crude product, the Rhizoma Picrorhizae glucoside II crude product mixed solvent crystallization and the recrystallization of ethyl acetate-dehydrated alcohol.
2, described according to claim 1, a kind of separation method of Rhizoma Picrorhizae glucoside II, it is characterized in that, compositions such as Rhizoma Picrorhizae glucoside II in the aqueous solution of the extract of Rhizoma Picrorhizae (Tibet picrorhiza rhizome or India's Rhizoma Picrorhizae) are after adsorbents adsorb is handled, separate the wash-out Rhizoma Picrorhizae glucoside II with basic solution, alkaline eluant neutralizes with acid.
3, described according to claim 1, alkaline eluant is crossed the chromatography column adsorption and enrichment Rhizoma Picrorhizae glucoside II that sorbent material is housed with the solution that contains Rhizoma Picrorhizae glucoside II after the acid neutralization, and the mixed solvent with ethanol, methyl alcohol or they and water carries out wash-out again.
4, described according to claim 1, a kind of crystallization purifying method of Rhizoma Picrorhizae glucoside II is characterized in that, the Rhizoma Picrorhizae glucoside II crude product mixed solvent crystallization and the recrystallization of ethyl acetate-dehydrated alcohol.
5, according to claim 1,2,3 described sorbent materials, can be the resin of nonpolar or low-pole, for example, styrene type (comprising vinyl toluene type, ethyl styrene type) resin, vinyl cyanide type resin also can be activated carbon.
6,, can be sodium hydroxide, potassium hydroxide, ammonia (ammoniacal liquor), solution that yellow soda ash, sodium bicarbonate were made into according to claim 1,2 described basic solutions.
7, requiring 1,2 described acid, can be organic acid, as formic acid, acetate, propionic acid and their aqueous solution that is made into, also can be ore deposit acid example hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid and their aqueous solution that is made into.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02149356 CN1218952C (en) | 2002-11-13 | 2002-11-13 | Preparing method for kutkin II crystal |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02149356 CN1218952C (en) | 2002-11-13 | 2002-11-13 | Preparing method for kutkin II crystal |
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| CN1500798A true CN1500798A (en) | 2004-06-02 |
| CN1218952C CN1218952C (en) | 2005-09-14 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013042131A1 (en) | 2011-09-23 | 2013-03-28 | M KUMAR, Anil | A process for preparation of synergistic herbal preparation of extracts picrorhiza kurroa and glycyrrhiza glabra having medicinal value |
| CN103936804A (en) * | 2014-03-31 | 2014-07-23 | 扬子江药业集团有限公司 | Preparation process of crystals of picroside II |
| CN104592325A (en) * | 2015-01-30 | 2015-05-06 | 济南东源生物医药技术有限公司 | Method for recycling picroside II from mother liquor after hydrothermal recrystallization of picroside II |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100371340C (en) * | 2004-11-26 | 2008-02-27 | 周亚伟 | Production of Rhizoma Picrorhizae glucoside II monomer and its drug form for treating hepatitis B |
-
2002
- 2002-11-13 CN CN 02149356 patent/CN1218952C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013042131A1 (en) | 2011-09-23 | 2013-03-28 | M KUMAR, Anil | A process for preparation of synergistic herbal preparation of extracts picrorhiza kurroa and glycyrrhiza glabra having medicinal value |
| CN103936804A (en) * | 2014-03-31 | 2014-07-23 | 扬子江药业集团有限公司 | Preparation process of crystals of picroside II |
| CN103936804B (en) * | 2014-03-31 | 2016-05-11 | 扬子江药业集团有限公司 | A kind of kutkin Ⅱcrystal preparation technology |
| CN104592325A (en) * | 2015-01-30 | 2015-05-06 | 济南东源生物医药技术有限公司 | Method for recycling picroside II from mother liquor after hydrothermal recrystallization of picroside II |
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| Publication number | Publication date |
|---|---|
| CN1218952C (en) | 2005-09-14 |
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