CN1166669C - Prepn process of sodium cantharidinate - Google Patents
Prepn process of sodium cantharidinate Download PDFInfo
- Publication number
- CN1166669C CN1166669C CNB021134901A CN02113490A CN1166669C CN 1166669 C CN1166669 C CN 1166669C CN B021134901 A CNB021134901 A CN B021134901A CN 02113490 A CN02113490 A CN 02113490A CN 1166669 C CN1166669 C CN 1166669C
- Authority
- CN
- China
- Prior art keywords
- cantharidin
- filtrate
- water
- acetone
- suction filtration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 title abstract 4
- 229910052708 sodium Inorganic materials 0.000 title abstract 4
- 239000011734 sodium Substances 0.000 title abstract 4
- DHZBEENLJMYSHQ-XCVPVQRUSA-N cantharidin Chemical compound C([C@@H]1O2)C[C@@H]2[C@]2(C)[C@@]1(C)C(=O)OC2=O DHZBEENLJMYSHQ-XCVPVQRUSA-N 0.000 claims abstract description 20
- 229940095758 cantharidin Drugs 0.000 claims abstract description 20
- 229930008397 cantharidin Natural products 0.000 claims abstract description 20
- DHZBEENLJMYSHQ-UHFFFAOYSA-N cantharidine Natural products O1C2CCC1C1(C)C2(C)C(=O)OC1=O DHZBEENLJMYSHQ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 239000002674 ointment Substances 0.000 claims abstract description 5
- 238000001953 recrystallisation Methods 0.000 claims abstract description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 239000000706 filtrate Substances 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 238000000967 suction filtration Methods 0.000 claims description 12
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 239000012043 crude product Substances 0.000 claims description 6
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 5
- 241000623906 Lytta vesicatoria Species 0.000 claims description 4
- 239000000284 extract Substances 0.000 claims description 4
- 239000000047 product Substances 0.000 claims description 4
- 238000004140 cleaning Methods 0.000 claims description 3
- 239000012141 concentrate Substances 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000012074 organic phase Substances 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 3
- 239000002775 capsule Substances 0.000 abstract description 2
- 238000001514 detection method Methods 0.000 abstract description 2
- 239000008187 granular material Substances 0.000 abstract description 2
- 239000003978 infusion fluid Substances 0.000 abstract description 2
- 239000007924 injection Substances 0.000 abstract description 2
- 238000002347 injection Methods 0.000 abstract description 2
- 239000007788 liquid Substances 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 abstract description 2
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 238000000605 extraction Methods 0.000 abstract 1
- 230000001093 anti-cancer Effects 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241000131283 Cantharis Species 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention discloses a technology for preparing sodium cantharidate, which comprises the following steps: cantharidin extraction, cantharidin recrystallization and sodium cantharidate preparation. The present invention has the advantages of reasonable technology, simplicity, practicality, high safety, stable performance of prepared finished products, high finished product purity and easy detection according to quality standards. The sodium cantharidate can be applied to the preparation of anti-tumor medicine of various preparations, such as injections, infusion solution, tablets, capsules, granules, oral liquid and ointment.
Description
The present invention is a kind of preparation technology of disodium cantharidinate.
Disodium cantharidinate is as antineoplastic pioneer's medicine, make the application modern biotechnology from cantharis, extract its effective constituent, the bound drug synthetic technology, through synthesizing, make with extra care, being transformed, its anticancer mechanism mainly is the protein synthesis of anticancer, influence its RNA and DNA, the growth division of final anticancer.The preparation technology of disodium cantharidinate raw material does not see so far the document record.
The objective of the invention is: provide a kind of with the Chinese blister beetle polypide through extract Cantharidin, recrystallization, produce and the technology of disodium cantharidinate elaboration.
The present invention is achieved in that it comprises that Cantharidin extracts, recrystallization, and several steps of preparation disodium cantharidinate:
(1) gets Chinese blister beetle polypide powder earlier and place container, add hydrochloric acid and soaked into 24 hours, add the acetone cold soaking again, shake up, soaked 72 hours, filter, filtrate places separating funnel, divide and get organic phase, put water-bath and reclaim acetone, add the washing of sherwood oil and dehydrated alcohol mixing solutions while hot to the ointment shape, through suction filtration, discard washings, with sherwood oil and dehydrated alcohol mixed solution cleaning product several, get yellow-white Cantharidin crude product again;
(2) get the ratio adding acetone soln of Cantharidin crude product in 1: 30 weight, make its dissolving in the heating in water bath backflow, treat that it dissolves the gac of back adding 0.3% fully, refluxed 30 minutes, suction filtration gets achromatism and clarity filtrate while hot, filtrate is placed flask, reclaim acetone to 1/5 of original volume, cooling back suction filtration gets white crystals;
(3) get the ratio adding acetone soln of Cantharidin elaboration in 1: 20 weight, heating in water bath refluxes and makes its dissolving, get simultaneously with the Cantharidin mol ratio be that to make concentration be 20% solution for 1: 2 sodium hydroxide adding distil water, treat that Cantharidin dissolves the back fully and adds sodium hydroxide solution reaction 1 hour, use water distilling apparatus instead and steam acetone to doing, the gac of adding 0.3%, refluxed 10 minutes, suction filtration while hot, get water white transparency filtrate, filtrate is diluted to original 10 times, put water-bath and concentrate, drying gets white crystalline powder.
The present invention has that technology is reasonable, simple and practical, security is good, the finished product stable in properties of preparation, and the purity height is easy to advantages such as detection by quality standard.Can be applicable to the antitumor drug production of multiple formulations such as injection, infusion solutions, tablet, capsule, granule, oral liquid and ointment.
Embodiments of the invention:
(1) gets Chinese blister beetle polypide powder 1kg, place the tool plug container of 10000ml, add hydrochloric acid and soaked into 24 hours, add acetone (or chloroform) cold soaking again, shake up, soaked 72 hours, filter, filtrate places separating funnel, divides and gets organic phase, put water-bath and reclaim acetone to the ointment shape, add sherwood oil and dehydrated alcohol (1: 1) mixing solutions while hot and wash in right amount,, discard washings through suction filtration, with sherwood oil and an amount of cleaning product several of dehydrated alcohol (1: 1) mixed solution, get yellow-white Cantharidin crude product again;
(2) get the ratio adding acetone soln of Cantharidin crude product in 1: 30 weight, make its dissolving in the heating in water bath backflow, treat that it dissolves the gac of back adding 0.3% fully, refluxed 30 minutes, suction filtration gets achromatism and clarity filtrate while hot, filtrate is placed round-bottomed flask, reclaim acetone to 1/5 of original volume, be positioned over suction filtration next day (filtrate preservation), get white crystals;
(3) get the ratio adding acetone soln of Cantharidin elaboration in 1: 20 weight, heating in water bath refluxes and makes its dissolving, get simultaneously with the Cantharidin mol ratio be that to make concentration be 20% solution for 1: 2 sodium hydroxide adding distil water, after treating that Cantharidin dissolves fully, add the sodium hydroxide solution that configures, reacted 1 hour, use water distilling apparatus instead and steam acetone, add 0.3% gac, refluxed 10 minutes to doing, suction filtration while hot, get water white transparency filtrate, filtrate is diluted to original 10 times, put water-bath and concentrate, drying gets white crystalline powder and is the disodium cantharidinate elaboration.
Claims (1)
1, a kind of preparation technology of disodium cantharidinate, it comprises that Cantharidin extracts, recrystallization, several steps of preparation disodium cantharidinate is characterized in that:
(1) gets Chinese blister beetle polypide powder earlier and place container, add hydrochloric acid and soaked into 24 hours, add the acetone cold soaking again, shake up, soaked 72 hours, filter, filtrate places separating funnel, divide and get organic phase, put water-bath and reclaim acetone, add the washing of sherwood oil and dehydrated alcohol mixing solutions while hot to the ointment shape, through suction filtration, discard washings, with sherwood oil and dehydrated alcohol mixed solution cleaning product several, get yellow-white Cantharidin crude product again;
(2) get the ratio adding acetone soln of Cantharidin crude product in 1: 30 weight, make its dissolving in the heating in water bath backflow, treat that it dissolves the gac of back adding 0.3% fully, refluxed 30 minutes, suction filtration gets achromatism and clarity filtrate while hot, filtrate is placed flask, reclaim acetone to 1/5 of original volume, cooling back suction filtration gets white crystals;
(3) get the ratio adding acetone soln of Cantharidin elaboration in 1: 20 weight, heating in water bath refluxes and makes its dissolving, get simultaneously with the Cantharidin mol ratio be that to make concentration be 20% solution for 1: 2 sodium hydroxide adding distil water, treat that Cantharidin dissolves the back fully and adds sodium hydroxide solution reaction 1 hour, use water distilling apparatus instead and steam acetone to doing, the gac of adding 0.3%, refluxed 10 minutes, suction filtration while hot, get water white transparency filtrate, filtrate is diluted to original 10 times, put water-bath and concentrate, drying gets white crystalline powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021134901A CN1166669C (en) | 2002-03-20 | 2002-03-20 | Prepn process of sodium cantharidinate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021134901A CN1166669C (en) | 2002-03-20 | 2002-03-20 | Prepn process of sodium cantharidinate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1374310A CN1374310A (en) | 2002-10-16 |
| CN1166669C true CN1166669C (en) | 2004-09-15 |
Family
ID=4742641
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB021134901A Expired - Lifetime CN1166669C (en) | 2002-03-20 | 2002-03-20 | Prepn process of sodium cantharidinate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1166669C (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1190190C (en) * | 2001-11-23 | 2005-02-23 | 王卫 | Antiviral and antibacterial cantharidinic anhydride medicine composition and its prepn process |
| CN101108854B (en) * | 2007-07-27 | 2010-05-26 | 贵州大学 | A kind of cantharidin separation and purification method |
| CN101108853B (en) * | 2007-07-27 | 2010-05-26 | 贵州大学 | Cantharidin separation and purification method |
| CN102146086B (en) * | 2011-04-12 | 2012-03-07 | 贵州金桥药业有限公司 | Preparation method of sodium cantharidate |
| CN102268006B (en) * | 2011-06-15 | 2013-08-14 | 北京联合大学生物化学工程学院 | Method for extracting cantharidin from compound enzyme |
| CN102276619A (en) * | 2011-06-21 | 2011-12-14 | 贵州金桥药业有限公司 | Method for preparing sodium canthanridate |
| CN102336765A (en) * | 2011-10-11 | 2012-02-01 | 江苏四环生物股份有限公司 | Method for extracting cantharidin from cantharides |
| CN102796794A (en) * | 2012-08-31 | 2012-11-28 | 哈尔滨工业大学 | Preparation method of cantharis toxin |
| CN103479642B (en) * | 2013-09-30 | 2015-04-29 | 贵州金桥药业有限公司 | Nano sodium cantharidinate composition and preparation method thereof |
| CN107936036A (en) * | 2017-11-29 | 2018-04-20 | 贵州柏强制药有限公司 | A kind of disodium cantharidinate and preparation method thereof |
-
2002
- 2002-03-20 CN CNB021134901A patent/CN1166669C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CN1374310A (en) | 2002-10-16 |
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| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Guizhou Baiqiang Pharmaceutical Co., Ltd. Assignor: Guizhou Junzhitang Pharmaceutical Co., Ltd. Contract record no.: 2011520000004 Denomination of invention: Preparing process of sodium cantharidinate Granted publication date: 20040915 License type: Exclusive License Open date: 20021016 Record date: 20110725 |
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| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170616 Address after: 550002 N-10, industrial zone, Nanming District, Guizhou, Guiyang Patentee after: Guizhou Baiqiang Pharmaceutical Co., Ltd. Address before: 550001 No. 85 Zhonghua Road, Guiyang, Guizhou Patentee before: Guizhou Junzhitang Pharmaceutical Co., Ltd. |
|
| CX01 | Expiry of patent term | ||
| CX01 | Expiry of patent term |
Granted publication date: 20040915 |