CN101108853B - Separation purification process of cantharidin - Google Patents
Separation purification process of cantharidin Download PDFInfo
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- CN101108853B CN101108853B CN200710077857A CN200710077857A CN101108853B CN 101108853 B CN101108853 B CN 101108853B CN 200710077857 A CN200710077857 A CN 200710077857A CN 200710077857 A CN200710077857 A CN 200710077857A CN 101108853 B CN101108853 B CN 101108853B
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Abstract
The invention discloses a cantharidin separation and purification method, which comprises the following steps: (1) the crude extract of the cantharidin is put in a vessel which is sealed, and is connected with air or CO2 and heated to 140 DEG C. to 150 DEG C., the crude extract of the cantharidin is melted and boiled and the large amount of white smog is taken to the cooling device by the air to gain the white power. (2) the ethyl acetate with 80 times volume is added to dissolve the white powder and is heated and refluxed under 80 DEG C. for 10min, and is filtered while heating and is coolednaturally to recrystallize, and conducts pumping filtration, is washed using the volume rate of 1 : 2 between the absolute ethyl alcohol and (30 DEG C. to 60 DEG C.) petroleum ether, and dried under room temperature to gain the cantharidin. The invention is characterized in that the invention has high product purity, high yield, low consumption of the organic solvent and simplified technology.
Description
Technical field
The invention belongs to chemical field, particularly separation purification method.
Background technology
Cantharidin is the monoterpenes defensive substance that is produced by Meloidae (Meloidae) insect.The history of human use's Cantharidin can be traced back to the China in B.C. 1,2nd century, the record of just existing medicinal " Chinese blister beetle " (Meloidae insect) in ancient medical book Shennong's Herbal.After this in famous medical book of successive dynasties all relevant for the record of blister beetle worm.Modern medicine thinks that Chinese blister beetle have antineoplastic pharmacological action, and cancers such as liver cancer, laryngocarcinoma, carcinoma of gastric cardia, esophagus cancer, digestive tract tumor are had significant curative effect, particularly primary hepatocarcinoma is had special efficacy.Except that anticancer, the function of the viral chronic hepatitis B of treatment, leukemia, rabies, dermovirus, fungi is still arranged, also have curative effects such as establishing-Yang, leukocyte increasing simultaneously.European countries' Cantharidin in the past commonly used is done ecbolic, pore forming material etc.; Nowadays often use Cantharidin and remove dermatosis chronic diseases such as sore on the skin, wart, knurl.
Chinese patent publication number CN1374310 discloses a kind of " preparation technology of disodium cantharidinate ", Chinese patent publication number: CN1966508 discloses " a kind of method of extracting Cantharidin ", all be to adopt recrystallization method extraction separation Cantharidin, technical process is handled the Chinese blister beetle polypide for adopting acid hydrolysis, use organic solvent extraction, adopt different ratios blended organic solvent washing, the back adopts recrystallization method to obtain the process of pure product.The main drawback of above technology is as follows: (1) in the process of operation, organic solvents such as a large amount of ethanol of the step consumption of washing, sherwood oil; Organic solvents such as the ethanol of these wastes simultaneously, sherwood oil are higher to operator's harm, and contaminate environment is serious.(2) operation is extensive, and the more Cantharidin of waste is serious waste to natural resources in the washing process; Productive rate is lower, causes cost to increase.(3) still have more Cantharidin can't separate behind the recrystallization with impurity.
Summary of the invention
The objective of the invention is to overcome above-mentioned shortcoming and increase a kind of finished product purity height, the productive rate height, the organic solvent consumption is little, the separation purification process of cantharidin of work simplification.
Separation purification process of cantharidin of the present invention may further comprise the steps:
(1) the Cantharidin crude extract is put into container, closed container feeds gas, is heated to 140-150 ℃, and to fusing of Cantharidin crude extract and boiling, white smoke a large amount of in the container are brought into refrigerating unit by gas, obtain white powder.
(2) add the acetic acid ethyl dissolution white powder of 80 times of volumes, 80 ℃ of reflux 10 minutes, filtered while hot, natural cooling crystallization, suction filtration is to wash at 1: 2 with dehydrated alcohol and (30 ℃-60 ℃) sherwood oil volume ratio, airing under the room temperature, promptly.
Above-mentioned separation purification process of cantharidin, wherein: gas is meant air or CO
2
Above-mentioned separation purification process of cantharidin, wherein the preparation method of crude extract is: the Chinese blister beetle polypide is placed 60 ℃ of oven dry down, be ground into the powder about 40 orders, put into reactor, add the trichloromethane of 3 times of weight, shake up, add the distilled water of 2 times of weight, add hydrochloric acid modulation pH=1, static 48h takes out separatory, filters, be concentrated into absence of liquid with Rotary Evaporators and flow out, promptly.
Above-mentioned separation purification process of cantharidin, wherein the preparation method of crude extract is: the Chinese blister beetle polypide is placed 60 ℃ of oven dry down, and pulverizer is ground into the powder about 40 orders, adds the hydrochloric acid soln of pH=1, soaks 48h, is drying to obtain.
The present invention compared with prior art, by above technical scheme as can be known, it can make Cantharidin separate well with impurity, purity and productive rate height; Need not repeatedly to wash, greatly saved organic dissolved consumptions such as ethanol, sherwood oil, reduced to operator's harm and to the pollution of environment; Simplify operation steps, thereby reduced cost effectively.
Embodiment
Embodiment 1:
The preparation of crude extract: the Chinese blister beetle polypide is placed 60 ℃ of oven dry down, and pulverizer is ground into the powder about 40 orders, puts into reactor, the trichloromethane that adds 3 times of weight, shake up, add the distilled water of 2 times of weight, add hydrochloric acid modulation pH=1, static 48h, take out separatory, filter, be concentrated into absence of liquid with Rotary Evaporators and flow out, promptly get the Cantharidin crude extract, standby.
Cantharidin crude extract 15g (Cantharidin content is 2.86g after measured) is put into container, closed container, bubbling air, heating, to the fusing of Cantharidin crude extract, and boiling, this moment, the fluid surface temperature was about 150 ℃, white smoke a large amount of in the container are brought into refrigerating unit by gas, obtain white powder.
Recrystallization process: the acetic acid ethyl dissolution white powder that adds 80 times of volumes, 80 ℃ of reflux 10 minutes, filtered while hot, natural cooling crystallization, suction filtration is used dehydrated alcohol: the washing of (30 ℃-60 ℃) sherwood oil=1: 2 (volume ratio), airing under the room temperature, obtain Cantharidin crystal 2 .38g (purity＞98%), the productive rate of Cantharidin is 83.22%.
Embodiment 2:
Cantharidin crude extract 15g (Cantharidin content is 2.86g after measured) is put into container, and closed container feeds CO
2, be heated to 150 ℃, the fusing of Cantharidin crude extract, white smoke a large amount of in the container are brought into refrigerating unit by gas, obtain white powder.
Recrystallization process is identical with embodiment 1.
Present embodiment obtains Cantharidin crystal 2 .31g (purity＞98%), and the productive rate of Cantharidin is 80.87%.
Embodiment 3:
Cantharidin crude extract 15g (Cantharidin content is 2.86g after measured) is put into container, closed container, bubbling air is heated to 140 ℃, the fusing of Cantharidin crude extract, white smoke a large amount of in the container are brought into refrigerating unit by gas, obtain white powder.
Recrystallization process is identical with embodiment 1.
Present embodiment obtains Cantharidin crystal 2 .23g (purity＞98%), and the productive rate of Cantharidin is 77.87%.
Claims (1)
1. separation purification process of cantharidin may further comprise the steps:
(1) the Cantharidin crude extract is put into container, closed container feeds gas, is heated to 140-150 ℃, and to fusing of Cantharidin crude extract and boiling, white smoke a large amount of in the container are brought into refrigerating unit by gas, obtain white powder;
(2) add the acetic acid ethyl dissolution white powder of 80 times of volumes, 80 ℃ of reflux 10 minutes, filtered while hot, natural cooling crystallization, suction filtration is to wash at 1: 2 with dehydrated alcohol and 30-60 ℃ of sherwood oil volume ratio, airing under the room temperature obtains the Cantharidin crystal;
Wherein: gas is meant air or CO
2
Wherein the preparation method of crude extract is: the Chinese blister beetle polypide is placed 60 ℃ of oven dry down, be ground into the powder about 40 orders, put into reactor, add the trichloromethane of 3 times of weight, shake up, the distilled water that adds 2 times of weight adds hydrochloric acid modulation pH=1, static 48h, take out separatory, filter, be concentrated into absence of liquid with Rotary Evaporators and flow out, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710077857A CN101108853B (en) | 2007-07-27 | 2007-07-27 | Separation purification process of cantharidin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710077857A CN101108853B (en) | 2007-07-27 | 2007-07-27 | Separation purification process of cantharidin |
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| Publication Number | Publication Date |
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| CN101108853A CN101108853A (en) | 2008-01-23 |
| CN101108853B true CN101108853B (en) | 2010-05-26 |
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| CN200710077857A Expired - Fee Related CN101108853B (en) | 2007-07-27 | 2007-07-27 | Separation purification process of cantharidin |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016118633A1 (en) * | 2015-01-20 | 2016-07-28 | Verrica Pharmaceuticals, Inc. | Quantification and preparation of pharmaceutical grade cantharidin |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102146086B (en) * | 2011-04-12 | 2012-03-07 | 贵州金桥药业有限公司 | Preparation method of sodium cantharidate |
| CN102276619A (en) * | 2011-06-21 | 2011-12-14 | 贵州金桥药业有限公司 | Method for preparing sodium canthanridate |
| EP3035992B1 (en) | 2013-08-21 | 2024-05-15 | Verrica Pharmaceuticals, Inc. | Compositions and systems for the treatment of cutaneous disorders |
| AU2015364524A1 (en) | 2014-12-17 | 2017-07-13 | Verrica Pharmaceuticals, Inc. | Commercially viable synthesis of cantharidin and bioactive cantharidin derivatives |
| CN106674247A (en) * | 2016-12-06 | 2017-05-17 | 广西壮族自治区兽医研究所 | Method for extracting cantharidin by using supercritical carbon dioxide |
| MX2019014667A (en) | 2017-06-06 | 2020-02-07 | Verrica Pharmaceuticals Inc | Treatment of cutaneous disorders. |
| USD900312S1 (en) | 2017-06-15 | 2020-10-27 | Verrica Pharmaceuticals, Inc. | Applicator |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1374310A (en) * | 2002-03-20 | 2002-10-16 | 贵州君之堂制药有限公司 | Prepn process of sodium cantharidinate |
| CN1966508A (en) * | 2006-08-18 | 2007-05-23 | 芜湖天远科技开发有限责任公司 | Method for extracting cantharidin |
-
2007
- 2007-07-27 CN CN200710077857A patent/CN101108853B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1374310A (en) * | 2002-03-20 | 2002-10-16 | 贵州君之堂制药有限公司 | Prepn process of sodium cantharidinate |
| CN1966508A (en) * | 2006-08-18 | 2007-05-23 | 芜湖天远科技开发有限责任公司 | Method for extracting cantharidin |
Non-Patent Citations (6)
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| 李晓飞等.斑蝥样品制备方法的改进及其成效比较.中成药 1.2007,(1),129-131. |
| 李晓飞等.斑蝥样品制备方法的改进及其成效比较.中成药 1.2007,(1),129-131. * |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016118633A1 (en) * | 2015-01-20 | 2016-07-28 | Verrica Pharmaceuticals, Inc. | Quantification and preparation of pharmaceutical grade cantharidin |
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