CN1438236A - Method for purifying Huanweihuangyangxing D and preparation thereof - Google Patents
Method for purifying Huanweihuangyangxing D and preparation thereof Download PDFInfo
- Publication number
- CN1438236A CN1438236A CN 03113000 CN03113000A CN1438236A CN 1438236 A CN1438236 A CN 1438236A CN 03113000 CN03113000 CN 03113000 CN 03113000 A CN03113000 A CN 03113000A CN 1438236 A CN1438236 A CN 1438236A
- Authority
- CN
- China
- Prior art keywords
- cyclovirobuxinum
- alcohol
- triethylamine
- hexanaphthene
- chloroform
- 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.)
- Granted
Links
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention refers to a purifying method of Chinese patent drug curing cardiovascular and cerebrovascular disease and preparation of the Chinese patent drug. It uses boxwood as raw material, crushes the boxwood into sawdust, wets and stirs evenly the sawdust by alcohol and ammonia to make pH alkaline; or, dips the sawdust by alcohol and ammonia to make pH alkaline, then filters to eliminate dipping liquid; then dips the sawdust in cyclodexane, filters to get cyclodexane, concentrates and recovers the cyclodexane to get dilute paste body and then places to crystallize, filters to get the crystal and washes by acetone to get boxnine, dissolves the boxnine by flowing phase, then pumps in making column to separate and purify, in sections collects and then makes concentration, crystallization and drying to get high-purity circular dimensional boxstar D.
Description
Technical field
The present invention relates to a kind of purification process of Chinese patent medicine for the treatment of cardiovascular and cerebrovascular diseases and its preparation.
Background technology
Cardiovascular and cerebrovascular diseases is common disease, frequently-occurring disease, and all patients need to adopt pharmacological agent.The effective constituent that the applicant extracts from the natural phant Ramulus Buxi Sinicae---Buxine (containing cyclovirobuxine about 70%), a large amount of clinical proofs through more than 20 years, Buxine is resisting myocardial ischemia, is reducing myocardial consumption of oxygen, is improving the myocardial anoxia ability, is improving coronary circulation, is dwindling myocardial infarct size, is strengthening myocardial contraction, preventing that aspect such as irregular pulse from having obtained certain curative effect, and toxic side effect is little, it is made tablet usually and is used for clinical, its drug effect is slower, and is efficient lower.
Summary of the invention
Purpose of the present invention is exactly in order to address the above problem, and it is fast to propose a kind of drug effect, the purification process of efficient high cyclovirobuxinum D and its preparation.
Technical solution of the present invention:
A kind of extracting method of cyclovirobuxinum D is characterized in that its employing following steps:
A. be raw material with the Ramulus Buxi Sinicae, it is ground into the wood chip shape;
B. wood chip shape Ramulus Buxi Sinicae is moistening and stir with alcohol and ammoniacal liquor, make their pH value be alkalescence; Perhaps, wood chip shape Ramulus Buxi Sinicae is soaked with alcohol and ammoniacal liquor, made their pH value be alkalescence, filter then and remove soak solution;
C. the wood chip shape Ramulus Buxi Sinicae after the moistening stirring is immersed in the hexanaphthene, gets rare shape lotion behind leaching hexanaphthene and the concentrated recovery hexanaphthene then and place crystallization again;
D. the above-mentioned xln of leaching promptly gets Buxine with washing with acetone;
E. above-mentioned Buxine is dissolved with moving phase, the composition of this moving phase and volume percent are:
Chloroform and/or normal hexane are 99.9-99.96%, and triethylamine is 0.04-0.1%;
Perhaps, this moving phase is made up of chloroform, normal hexane, methyl alcohol and triethylamine, and the proportioning between them is:
Chloroform: normal hexane: methyl alcohol: triethylamine=1: 0.8-2: 0.3-0.8: 0.01-0.03,
Pump into then and carry out separation and purification in the preparative column, Fractional Collections reconcentration, crystallization, oven dry promptly get highly purified cyclovirobuxinum D.
A kind of injection of cyclovirobuxinum D is characterized in that cyclovirobuxinum D and glucose or sodium-chlor are added in the water for injection, transfers its pH value to be controlled at 5-6 with diluted acid again.
A kind of dispersible tablet of cyclovirobuxinum D is characterized in that making according to a conventional method with cyclovirobuxinum D and medical vehicle that the inventive method is extracted.
Ramulus Buxi Sinicae is as medicinal, and in Compendium of Materia Medica the 36 volume woody part three of LI Shi-Zhen medicinal record is just arranged: " the smell hardship is put down, and is nontoxic to claim it.Cure mainly madam's difficult labour,, go in the DASHENG SAN and use.The main again heat moon is given birth to scabies, mashes and is coated with it." cyclovirobuxinum D is little leaf boxwood Buxus MicrophyllaSieb.et Zucc.Var.Sinica Rehd.et Wils.The present invention adopts HPLC preparative column technology, the cyclosiloxane monomer virobuxine D of having purified (content is more than 90%) according to the requirement of the modernization of Chinese medicine from Buxine.Highly purified ring dimension is yellow raises the preparation that star D makes and not only has vitality at home, also is expected to enter the world market, also meets the requirement of U.S. FDA simultaneously.This current state-of-the-art purification technique of high performance preparative liquid chromatography has been adopted in the purification of cyclovirobuxinum D, has adapted to the requirement of Chinese medicine west system, lays a good foundation for Chinese medicine enters the world market.The present invention is along with novel form continues to bring out, deepening continuously of the modernization of Chinese medicine, after highly purified cyclovirobuxinum D made cyclovirobuxinum D glucose injection and cyclovirobuxinum D sodium chloride injection (100ml:6mg), medicament directly injects human body by vein, and is rapid-action, can reach focus rapidly, relief of symptoms, need not pass through the absorption stage, effect is specially adapted to rescue the urgent patient rapidly.The present invention also can be made into dispersible tablet, and it is than conventional tablet easy administration, and Ke Huashui is convenient to the elderly or the child takes, and absorption is fast, bioavailability is high, also can work as conventional tablet and swallow.Dispersible tablet has the advantage that is easy to carry, transports again.
Embodiment
The purification process of cyclovirobuxinum D of the present invention is as follows:
1, with the Ramulus Buxi Sinicae is raw material, it is ground into the wood chip shape.
2, wood chip shape Ramulus Buxi Sinicae is moistening and stir with alcohol and ammoniacal liquor, make their pH value be alkalescence.Perhaps, also wood chip shape Ramulus Buxi Sinicae can be soaked with alcohol and ammoniacal liquor, be made their pH value be alkalescence, filter then and remove soak solution.It is alcohol more than 75% that described alcohol is preferably selected concentration for use, and the best is 95% alcohol, and ammoniacal liquor is preferably selected strong aqua for use, and described pH value the best is 9.
3, the wood chip shape Ramulus Buxi Sinicae after moistening stirring or the immersion is immersed in the hexanaphthene, leaching hexanaphthene and the concentrated hexanaphthene that reclaims get rare shape lotion and place crystallization more then.
4, the above-mentioned xln of leaching promptly gets Buxine (it contains about the about 40-70% of cyclovirobuxinum D) with washing with acetone.
5, above-mentioned Buxine is dissolved with moving phase, the composition of this moving phase and volume percent are: chloroform and/or normal hexane are 99.9-99.96%, and triethylamine is 0.04-0.1%.Perhaps, this moving phase also can be made up of chloroform, normal hexane, methyl alcohol and triethylamine, and the proportioning between them is:
Chloroform: normal hexane: methyl alcohol: triethylamine=1: 0.8-2: 0.3-0.8: 0.01-0.03, their best proportioning=4: 4: 2: 0.08.Pump into then and carry out separation and purification in the preparative column, Fractional Collections reconcentration, crystallization, oven dry promptly get highly purified cyclovirobuxinum D.
Preparative column in the separation and purification operation of the present invention should be silicagel column.
The present invention is in above-mentioned steps 3, and the hexanaphthene of recovery can be applied mechanically repeatedly, and the hexanaphthene soak time was generally more than 2 hours.
Embodiment:
Get the Ramulus Buxi Sinicae wood chip of 300kg, add the alcohol of 30kg and the mixed solution of ammoniacal liquor then, they are stirred, transferring pH value is 7.5, and the purpose that adds alcohol is in order to destroy the cellularstructure of Ramulus Buxi Sinicae, so that the solvent porous advances the Chinese littleleaf box cell.Ramulus Buxi Sinicae after stirring is immersed in the hexanaphthene of 200kg, standing over night, filtering Ramulus Buxi Sinicae wood chip then, and filtering hexanaphthene liquid is concentrated, reclaims, the rare shape lotion after concentrating is placed crystallization, and the hexanaphthene of recovery can be applied mechanically repeatedly.The above-mentioned crystallization of leaching promptly gets about 30g Buxine with washing with acetone.Preparation moving phase, can select the moving phase of chloroform 99.9ml and triethylamine 0.1ml preparation 100ml for use, also can select for use the triethylamine of normal hexane 99.95ml and 0.05ml to be mixed with the moving phase of 100ml, or be mixed with the moving phase of 100ml with the triethylamine of the normal hexane of 50ml chloroform, 49.91ml and 0.09ml, or being mixed with the moving phase of 100ml with the triethylamine of 35ml chloroform, 50ml normal hexane, 14.3ml methyl alcohol and 0.7ml, best proportioning is: get the moving phase that 40ml chloroform, 40ml normal hexane, 19.2ml methyl alcohol and 0.8ml triethylamine are mixed with 100ml.
Above-mentioned 30g Buxine is dissolved with the 100ml moving phase for preparing, pump into high-pressure pump then and carry out separation and purification in the silicagel column, the content of Fractional Collections and detection ring virobuxine D, merge the part 90% or more, after concentrated, crystallization, the oven dry cyclovirobuxinum D about can about 5g.
Most preferred embodiment: the alcohol and the strong aqua mixed solution 30kg of adding 95% in 300kg Ramulus Buxi Sinicae wood chip, stir, the pH value of transferring them is 9.Other step is constant, can get the about 150g of intermediate Buxine, finally obtains cyclovirobuxinum D and can be about 45g.
The method of purification of cyclovirobuxinum D: chromatographic condition: instrument: Waters pump; Chromatographic column: preparation silicagel column.Moving phase: normal hexane, chloroform, methyl alcohol, triethylamine.Sample introduction, sampling is collected.The liquid of collecting is spin-dried for Rotary Evaporators, reclaims moving phase.
The cyclovirobuxinum D that the inventive method is extracted can be mixed with injection, also can be made into dispersible tablet.The compound method of its injection is:
It is 5-6 that cyclovirobuxinum D is transferred pH value with acid, and ultrasonic dissolution, adds the water for injection dilution then, adds an amount of glucose or sodium-chlor again and promptly makes the cyclovirobuxinum D injection liquid.Described acid can be selected hydrochloric acid, Glacial acetic acid etc. for use.
Dispersible tablet of the present invention can make according to a conventional method with cyclovirobuxinum D and pharmaceutical excipient.
Claims (9)
1, a kind of purification process of cyclovirobuxinum D is characterized in that its employing following steps:
A. be raw material with the Ramulus Buxi Sinicae, it is ground into the wood chip shape;
B. wood chip shape Ramulus Buxi Sinicae is moistening and stir with alcohol and ammoniacal liquor, make their pH value be alkalescence; Perhaps, wood chip shape Ramulus Buxi Sinicae is soaked with alcohol and ammoniacal liquor, made their pH value be alkalescence, filter then and remove soak solution;
C. the wood chip shape Ramulus Buxi Sinicae after moistening stirring or the immersion is immersed in the hexanaphthene, leaching hexanaphthene and the concentrated hexanaphthene that reclaims get rare shape lotion and place crystallization more then;
D. the above-mentioned xln of leaching promptly gets Buxine with washing with acetone;
E. above-mentioned Buxine is dissolved with moving phase, the composition of this moving phase and volume percent are:
Chloroform and/or normal hexane are 99.9-99.96%, and triethylamine is 0.04-0.1%;
Perhaps, this moving phase is made up of chloroform, normal hexane, methyl alcohol and triethylamine, and the proportioning between them is:
Chloroform: normal hexane: methyl alcohol: triethylamine=1: 0.8-2: 0.3-0.8: 0.01-0.03,
Pump into then and carry out separation and purification in the preparative column, Fractional Collections reconcentration, crystallization, oven dry promptly get highly purified cyclovirobuxinum D.
2, by the purification process of the described cyclovirobuxinum D of claim 1, it is characterized in that described moisteningly or soak alcohol and the ammoniacal liquor of wood chip shape Ramulus Buxi Sinicae, it is alcohol more than 75% that its alcohol is selected concentration for use, and ammoniacal liquor is selected strong aqua for use, and their PH is 9.
3,, it is characterized in that it is 95% alcohol that described alcohol is selected concentration for use by the purification process of the described cyclovirobuxinum D of claim 2.
4, by the purification process of the described cyclovirobuxinum D of claim 1, it is characterized in that the described moving phase of being made up of chloroform, normal hexane, methyl alcohol and triethylamine, the proportioning between them is:
Chloroform: normal hexane: methyl alcohol: triethylamine=4: 4: 2: 0.08.
5, by the purification process of the described cyclovirobuxinum D of claim 1, it is characterized in that the preparative column in the described separation and purification operation is a silicagel column.
6, by the purification process of the described cyclovirobuxinum D of claim 1, it is characterized in that in described step c, the hexanaphthene of recovery should be applied mechanically repeatedly; The hexanaphthene soak time is more than 2 hours.
7, a kind of injection of cyclovirobuxinum D is characterized in that it is 5-6 that cyclovirobuxinum D is transferred pH value with acid, and ultrasonic dissolution, adds the water for injection dilution then, adds an amount of glucose or sodium-chlor again and promptly makes the cyclovirobuxinum D injection liquid.
8,, it is characterized in that described acid selects hydrochloric acid, Glacial acetic acid for use by the injection of the described cyclovirobuxinum D of claim 7.
9, a kind of dispersible tablet of cyclovirobuxinum D is characterized in that making according to a conventional method with cyclovirobuxinum D and pharmaceutical excipient that claim 1 method is extracted.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031130003A CN1182151C (en) | 2003-03-19 | 2003-03-19 | Method for purifying Huanweihuangyangxing D and preparation thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031130003A CN1182151C (en) | 2003-03-19 | 2003-03-19 | Method for purifying Huanweihuangyangxing D and preparation thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410062752 Division CN1864690A (en) | 2003-03-19 | 2003-03-19 | Preparation of cyclovirobuxinum D |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1438236A true CN1438236A (en) | 2003-08-27 |
| CN1182151C CN1182151C (en) | 2004-12-29 |
Family
ID=27674024
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031130003A Expired - Fee Related CN1182151C (en) | 2003-03-19 | 2003-03-19 | Method for purifying Huanweihuangyangxing D and preparation thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1182151C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112094312A (en) * | 2019-06-18 | 2020-12-18 | 江苏晶立信医药科技有限公司 | Crystal form A of cyclovirobuxine D dihydrochloride |
| CN112521440A (en) * | 2020-05-25 | 2021-03-19 | 南京经皮科技有限公司 | Method for purifying cyclochrysine D |
-
2003
- 2003-03-19 CN CNB031130003A patent/CN1182151C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112094312A (en) * | 2019-06-18 | 2020-12-18 | 江苏晶立信医药科技有限公司 | Crystal form A of cyclovirobuxine D dihydrochloride |
| CN112094312B (en) * | 2019-06-18 | 2022-03-11 | 江苏晶立信医药科技有限公司 | Crystal form A of cyclovirobuxine D dihydrochloride |
| CN112521440A (en) * | 2020-05-25 | 2021-03-19 | 南京经皮科技有限公司 | Method for purifying cyclochrysine D |
| CN112521440B (en) * | 2020-05-25 | 2021-08-20 | 南京经皮科技有限公司 | Method for purifying cyclochrysine D |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1182151C (en) | 2004-12-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101229199B (en) | Integrative extract method of multi-active ingredient in cordyceps militaris mycelium | |
| CN1164582C (en) | Process for preparing danshen salviandic acid | |
| CN101560201B (en) | Technique for extracting puerarin and diverse medical ingredients from root of kudzuvine | |
| CN1179941C (en) | Process for extracting 4-hydroxy-isoleucine and by-products including feungreek gum from seed of feungreek | |
| CN111233658B (en) | Method for extracting shikimic acid and quinic acid from folium ginkgo | |
| CN1257182C (en) | Method for preparing enoxolone | |
| CN1229324C (en) | Extraction process of tanshin general phenolic acid and its prepn and use | |
| CN1182151C (en) | Method for purifying Huanweihuangyangxing D and preparation thereof | |
| CN1453277A (en) | Meadowrueleaf corydalis general alkaloid and its prepn and application | |
| CN1785308A (en) | Extraction technology of plant total alkaloid extract having anti tumour action and its preparation | |
| CN107880149A (en) | A kind of extraction process of Dendrobium officinale polysaccharide | |
| CN1384110A (en) | Prepn of hederagenin | |
| CN101792394B (en) | Extraction separation method of L-synephrine | |
| CN110078667A (en) | A method of extracting huperzine | |
| CN1864690A (en) | Preparation of cyclovirobuxinum D | |
| CN1107680C (en) | Solasodine hydrochlorate and productive method and application in medicine | |
| CN1272311C (en) | Extracting method for natural amino acid mixture with rich 4-hydroxy-isolecine | |
| CN1634214A (en) | Method for preparing acanthopanax injectio | |
| CN101613387A (en) | The method of extracting purified puerarin by utilizing ion-exchange fiber | |
| CN1872101A (en) | Distillage of Ardisia chinensis Benth of possessing function of antivirus, distilling method and application | |
| CN1267665A (en) | Preparation of notoginseng essence as efficient hemostatic material | |
| CN1600357A (en) | Effective position of pilose asiabell root, preparation, medication use and preparation method | |
| CN102838692A (en) | Extraction method for heparin sodium | |
| CN1253430C (en) | Method for extracting 4-hydroxyl-isoleucine extract and three by-product from endosperm removed fenugreek seed powder | |
| CN1224023A (en) | Medicinal use of total sterone in Radix Rhapontici and preparing method thereof |
Legal Events
| 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 | ||
| C56 | Change in the name or address of the patentee |
Owner name: NANJING XIAOYING PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: NANJING XIAOYING PHARMACEUTICAL FACTORY Owner name: NANJING XIAOYING MEDICINE GROUP CO.,LTD. Free format text: FORMER NAME: NANJING XIAOYING PHARMACEUTICAL CO., LTD. |
|
| CP03 | Change of name, title or address |
Address after: No. 18, Shun Fa Road, Dongshan high tech Industrial Zone, Nanjing, Jiangsu, Jiangning: 211103 Patentee after: Nanjing Xiaoying Pharmaceutical Group Co.,Ltd. Address before: No. 18, Shun Fa Road, Dongshan high tech Industrial Zone, Nanjing, Jiangsu, Jiangning: 211103 Patentee before: Nanjing Xiaoying Pharmaceutical Co.,Ltd. Address after: No. 18, Shun Fa Road, Dongshan high tech Industrial Zone, Nanjing, Jiangsu, Jiangning: 211103 Patentee after: Nanjing Xiaoying Pharmaceutical Co.,Ltd. Address before: Nanjing City, Jiangsu province Longpan Road No. 29 zip code: 210016 Patentee before: XIAOYING PHARMACEUTICAL FACTOR |
|
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20041229 Termination date: 20120319 |