CN102633793A - Preparation method for extracting and separating emetini hydrochloridium and cephaeline hydrochloride from ipecace - Google Patents
Preparation method for extracting and separating emetini hydrochloridium and cephaeline hydrochloride from ipecace Download PDFInfo
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- CN102633793A CN102633793A CN2012101131523A CN201210113152A CN102633793A CN 102633793 A CN102633793 A CN 102633793A CN 2012101131523 A CN2012101131523 A CN 2012101131523A CN 201210113152 A CN201210113152 A CN 201210113152A CN 102633793 A CN102633793 A CN 102633793A
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- hydrochloride
- solution
- cephaeline
- ipecac
- emetine
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- APCJEUAHYFIVKA-UHFFFAOYSA-N 5-trimethylsilylthiophene-2-carboxylic acid Chemical compound C[Si](C)(C)C1=CC=C(C(O)=O)S1 APCJEUAHYFIVKA-UHFFFAOYSA-N 0.000 title claims abstract description 65
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 90
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 88
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 85
- 229960001923 emetine hydrochloride Drugs 0.000 claims description 65
- HUEYSSLYFJVUIS-MRFSYGAJSA-N (2s,3r,11bs)-2-[[(1r)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl]methyl]-3-ethyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1h-benzo[a]quinolizine;hydron;chloride Chemical compound Cl.N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@@H]1CC HUEYSSLYFJVUIS-MRFSYGAJSA-N 0.000 claims description 61
- 244000284152 Carapichea ipecacuanha Species 0.000 claims description 50
- 239000009471 Ipecac Substances 0.000 claims description 48
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 48
- 229940029408 ipecac Drugs 0.000 claims description 48
- 238000000605 extraction Methods 0.000 claims description 47
- 238000000034 method Methods 0.000 claims description 34
- 238000000926 separation method Methods 0.000 claims description 29
- 238000000746 purification Methods 0.000 claims description 28
- 239000000463 material Substances 0.000 claims description 25
- 239000007788 liquid Substances 0.000 claims description 24
- 239000003960 organic solvent Substances 0.000 claims description 20
- 238000007670 refining Methods 0.000 claims description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 18
- 230000002378 acidificating effect Effects 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 16
- 238000002953 preparative HPLC Methods 0.000 claims description 16
- 239000006228 supernatant Substances 0.000 claims description 16
- 230000006837 decompression Effects 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 13
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 12
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 12
- 239000012071 phase Substances 0.000 claims description 12
- 238000001228 spectrum Methods 0.000 claims description 12
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 6
- 239000007791 liquid phase Substances 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 2
- 238000004108 freeze drying Methods 0.000 abstract description 25
- 229930013930 alkaloid Natural products 0.000 abstract description 8
- 230000000954 anitussive effect Effects 0.000 abstract description 2
- 229940124584 antitussives Drugs 0.000 abstract description 2
- 239000003172 expectorant agent Substances 0.000 abstract description 2
- 230000003419 expectorant effect Effects 0.000 abstract description 2
- 241000607292 Maguireothamnus speciosus Species 0.000 abstract 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 abstract 1
- 239000002895 emetic Substances 0.000 abstract 1
- 239000000284 extract Substances 0.000 description 14
- -1 emetine hydrochlorides Chemical class 0.000 description 9
- 238000001035 drying Methods 0.000 description 8
- 241000196324 Embryophyta Species 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 239000013558 reference substance Substances 0.000 description 4
- 238000002137 ultrasound extraction Methods 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- 230000008676 import Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 241000150853 Sanguirana varians Species 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- PTCGDEVVHUXTMP-UHFFFAOYSA-N flutolanil Chemical compound CC(C)OC1=CC=CC(NC(=O)C=2C(=CC=CC=2)C(F)(F)F)=C1 PTCGDEVVHUXTMP-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 208000008710 Amebic Dysentery Diseases 0.000 description 1
- 206010001986 Amoebic dysentery Diseases 0.000 description 1
- 241001145897 Cephaelis Species 0.000 description 1
- MBYXEBXZARTUSS-QLWBXOBMSA-N Emetamine Natural products O(C)c1c(OC)cc2c(c(C[C@@H]3[C@H](CC)CN4[C@H](c5c(cc(OC)c(OC)c5)CC4)C3)ncc2)c1 MBYXEBXZARTUSS-QLWBXOBMSA-N 0.000 description 1
- 241001358279 Malaya Species 0.000 description 1
- 241000123069 Ocyurus chrysurus Species 0.000 description 1
- 241001107098 Rubiaceae Species 0.000 description 1
- AUVVAXYIELKVAI-UHFFFAOYSA-N SJ000285215 Natural products N1CCC2=CC(OC)=C(OC)C=C2C1CC1CC2C3=CC(OC)=C(OC)C=C3CCN2CC1CC AUVVAXYIELKVAI-UHFFFAOYSA-N 0.000 description 1
- 241000594182 Sarcophaga sigma Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229960002694 emetine Drugs 0.000 description 1
- AUVVAXYIELKVAI-UWBTVBNJSA-N emetine Natural products N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@H]1CC AUVVAXYIELKVAI-UWBTVBNJSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
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Abstract
The invention discloses a preparation method for separating emetini hydrochloridium and cephaeline hydrochloride from ipecace. The maguireothamnus speciosus ipecace has the functions of being emetic, antitussive and expectorant, and contains six alkaloids such as emetini hydrochloridium, cephaeline hydrochloride and the like at present. The preparation method provided by the invention can be used for preparing the emetini hydrochloridium and cephaeline hydrochloride with the content which is more than 98% from the ipecace by the following steps of extracting, purifying, freeze drying, etc.
Description
Technical field
The present invention relates to a kind of method of from ipecac, extracting refining emetine hydrochloride and Cephaeline Hydrochloride.
Background technology
Ipecac is the perennial evergreen stunted brushwood, is Rubiaceae, and nine joint belongs to.It is cylindrical that root is distortion, burgundy, and stem is dark green, and branch matter is soft, floral white.Ipecac mainly originates in Brazilian moist forest area, and commodity are called Uragoga ipecacuanha Baillon.Ipecac is planted successfully on the Bengal of India east, Burma, Federation of Malaya, Singapore, Indonesia and other places, and also there is introducing culture in China Guangdong, Yunnan, Taiwan.
Mainly containing ether dissolubility total alkaloids in the ipecac, is main with emetine hydrochloride and Cephaeline Hydrochloride again wherein.Ipecac is the medicine of South America Indian, imports Europe in 1672, is considered to the medicine of dysentery, and is better to the amebic dysentery result of treatment.The application of ipecac now is more extensive, as the vomitive determined curative effect, even median dose also can stimulate vomiting to be eliminated until gastric content; The low dose of use is strong expectorant, is usually used in many antitussive, is used for bronchitis, pertussal treatment.Ipecac has certain toxicity; Its toxic component and therapeutic component all are to be master's total alkaloids with emetine hydrochloride and Cephaeline Hydrochloride, have remarkable meaning thereby this invention improves drug safety property to the accurate control of emetine hydrochloride in the preparation from now on and Cephaeline Hydrochloride.
Because ipecac belongs to import drugs, and is domestic very few to its correlative study, also lack the corresponding document that extracts process for purification.Report and adopt ethanol that ipecac is carried out supersound extraction; Can effectively extract ether dissolubility biology total alkali [Xu Liying, Song Weifeng; The research of ipecac ether dissolubility alkaloid extracting technique; Preparation and technology, April 8 in 2011 were rolled up o. 11th] but ether dissolubility vegeto-alkali has comprised many compositions, and do not relate to the extraction process for purification of emetine hydrochloride and Cephaeline Hydrochloride.
Summary of the invention
The present invention provides a kind of method of from ipecac, extracting refining emetine hydrochloride and Cephaeline Hydrochloride, and this method comprises the steps:
A, supersound extraction: get the ipecac medicinal material, pulverize, add acidic ethanol, supersound extraction gets extracting solution A;
B, concentrated: extracting solution A is centrifugal, gets supernatant, waves most solvent, regulates pH value to alkalescence, gets liquid concentrator B;
C, extraction: liquid concentrator B collects ether layer with extracted with diethyl ether, volatilizes solvent, gets residue C;
D, separation and purification: with residue C dissolving, inject the preparation liquid phase, adopt preparative hplc to carry out separation and purification, adopt the ODS post to separate, moving phase is acetonitrile: triethylamine; According to detecting the corresponding bands of a spectrum of collection of illustrative plates emetine hydrochloride and Cephaeline Hydrochloride, fraction collection solution D and solution E respectively;
E, lyophilize: after the solution D that obtains and solution E be concentrated into organic solvent respectively and remove, regulate pH value, carry out lyophilize, obtain emetine hydrochloride and Cephaeline Hydrochloride to acid.
The acidic ethanol of indication in this method is meant the ethanol with desired concn, adds appropriate hydrochloric acid, is configured to the ethanol of required acidity.
The present invention extracts refining emetine hydrochloride and Cephaeline Hydrochloride from ipecac method preferably includes following steps:
A, supersound extraction: get the ipecac medicinal material, pulverize, add the acidic ethanol that 10-40 doubly measures 1%-3%, alcohol concn is 50-90%, supersound extraction 0.5-2 hour, gets extracting solution A;
B, concentrated: extracting solution A is centrifugal, gets supernatant, and most ethanol is waved in 40-60 ℃ of decompression, regulates pH value to 10-12, gets liquid concentrator B;
C, extraction: liquid concentrator B collects ether layer with volume extracted with diethyl ether 1-4 time, volatilizes solvent, residue C;
D, separation and purification: C dissolves with acetonitrile with residue, is settled to be equivalent to the every ml of crude drug amount 1g, adopts preparative hplc to carry out separation and purification, chromatographic condition: chromatographic column: ODS chromatographic column; Moving phase is acetonitrile: 0.05% triethylamine, room temperature volume ratio are 40-45: 60-55; Flow velocity is 1.0ml/min-5.0ml/min; According to detecting the corresponding bands of a spectrum of collection of illustrative plates emetine hydrochloride and Cephaeline Hydrochloride, fraction collection solution D and solution E respectively;
E, lyophilize: the solution D that obtains and solution E are evaporated to respectively after organic solvent removes, and adjustment pH value is carried out lyophilize to 3-5, obtains emetine hydrochloride and Cephaeline Hydrochloride.
The present invention extracts refining emetine hydrochloride and Cephaeline Hydrochloride from ipecac method more preferably comprises the steps:
A, supersound extraction: get the ipecac medicinal material, pulverize, add the acidic ethanol of 20 times of amounts 1%, alcohol concn is 70%, and supersound extraction 1 hour gets extracting solution A;
B, concentrated: extracting solution A is centrifugal, gets supernatant, and most ethanol is waved in 40 ℃ of decompressions, regulates pH value to 10, gets liquid concentrator B;
C, extraction: liquid concentrator B collects ether layer with the extracted with diethyl ether of same volume 4 times, volatilizes solvent, residue C;
D, separation and purification: C dissolves with acetonitrile with residue, is settled to be equivalent to the every ml of crude drug amount 1g, adopts preparative hplc to carry out separation and purification, chromatographic condition: chromatographic column: C
18Chromatographic column; Detect wavelength: 283nm; Moving phase is acetonitrile: 0.05% triethylamine, room temperature volume ratio are 45: 55; Flow velocity is 5.0ml/min; According to detecting the corresponding bands of a spectrum of collection of illustrative plates emetine hydrochloride and Cephaeline Hydrochloride, fraction collection solution D and solution E respectively;
E, lyophilize: the solution D that obtains and solution E are evaporated to respectively after organic solvent removes, and adjustment pH value to 4 is carried out lyophilize, obtains emetine hydrochloride and Cephaeline Hydrochloride.
The present invention extracts refining emetine hydrochloride and Cephaeline Hydrochloride from ipecac method more preferably also comprises the steps:
A, supersound extraction: get the ipecac medicinal material, pulverize, add the acidic ethanol of 30 times of amounts 3%, alcohol concn is 90%, and supersound extraction 2 hours gets extracting solution A;
B, concentrated: extracting solution A is centrifugal, gets supernatant, and most ethanol is waved in 60 ℃ of decompressions, regulates pH value to 12, gets liquid concentrator B;
C, extraction: liquid concentrator B collects ether layer with the extracted with diethyl ether of same volume 1 time, volatilizes solvent, residue C;
D, separation and purification: C dissolves with acetonitrile with residue, is settled to be equivalent to the every ml of crude drug amount 1g, adopts preparative hplc to carry out separation and purification, chromatographic condition: chromatographic column: C
18Chromatographic column; Detect wavelength: 283nm; Moving phase is acetonitrile: 0.05% triethylamine, room temperature volume ratio are 40: 60; Flow velocity is 1.0ml/min; According to detecting the corresponding bands of a spectrum of collection of illustrative plates emetine hydrochloride and Cephaeline Hydrochloride, fraction collection solution D and solution E respectively;
E, lyophilize: the solution D that obtains and solution E are evaporated to respectively after organic solvent removes, add a small amount of Hydrogen chloride, adjustment pH value to 5 is carried out lyophilize, obtains emetine hydrochloride and Cephaeline Hydrochloride.
The present invention extracts refining emetine hydrochloride and Cephaeline Hydrochloride from ipecac method more preferably also comprises the steps:
A, supersound extraction: get the ipecac medicinal material, pulverize, add the acidic ethanol of 10 times of amounts 2%, alcohol concn is 60%, and supersound extraction 0.5 hour gets extracting solution A;
B, concentrated: extracting solution A is centrifugal, gets supernatant, and most ethanol is waved in 50 ℃ of decompressions, regulates pH value to 11, gets liquid concentrator B;
C, extraction: liquid concentrator B collects ether layer with the extracted with diethyl ether of same volume 3 times, volatilizes solvent, residue C;
D, separation and purification: C dissolves with acetonitrile with residue, is settled to be equivalent to the every ml of crude drug amount 1g, adopts preparative hplc to carry out separation and purification, chromatographic condition: chromatographic column: C
18Chromatographic column; Detect wavelength: 283nm; Moving phase is acetonitrile: 0.05% triethylamine, room temperature volume ratio are 45: 55; Flow velocity is 3.0ml/min; According to detecting the corresponding bands of a spectrum of collection of illustrative plates emetine hydrochloride and Cephaeline Hydrochloride, fraction collection solution D and solution E respectively;
E, lyophilize: the solution D that obtains and solution E are evaporated to respectively after organic solvent removes, add a small amount of Hydrogen chloride, adjustment pH value to 3 is carried out lyophilize, obtains emetine hydrochloride and Cephaeline Hydrochloride.
The present invention extracts refining emetine hydrochloride and Cephaeline Hydrochloride from ipecac method more preferably also comprises the steps:
A, supersound extraction: get the ipecac medicinal material, pulverize, add the acidic ethanol of 40 times of amounts 3%, alcohol concn is 50%, and supersound extraction 1.5 hours gets extracting solution A;
B, concentrated: extracting solution A is centrifugal, gets supernatant, and most ethanol is waved in 60 ℃ of decompressions, regulates pH value to 10, gets liquid concentrator B;
C, extraction: liquid concentrator B collects ether layer with volume extracted with diethyl ether 2 times, volatilizes solvent, residue C;
D, separation and purification: C dissolves with acetonitrile with residue, is settled to be equivalent to the every ml of crude drug amount 1g, adopts preparative hplc to carry out separation and purification, chromatographic condition: chromatographic column: C
18Chromatographic column; Detect wavelength: 283nm; Moving phase is acetonitrile: 0.05% triethylamine, room temperature volume ratio are 45: 55; Flow velocity is 4.0ml/min; According to detecting the corresponding bands of a spectrum of collection of illustrative plates emetine hydrochloride and Cephaeline Hydrochloride, fraction collection solution D and solution E respectively;
E, lyophilize: the solution D that obtains and solution E are evaporated to respectively after organic solvent removes, and adjustment pH value to 5 is carried out lyophilize, obtains emetine hydrochloride and Cephaeline Hydrochloride.
The present invention extracts from ipecac in the method for refining emetine hydrochloride and Cephaeline Hydrochloride, and adjustment of acidity ethanol uses hydrochloric acid, and regulator solution alkalescence is used ammonia solution.
The present invention also protects the application of refining emetine hydrochloride in preparation treatment loeschiasis medicine that obtains according to above-mentioned arbitrary described method of from ipecac, extracting refining emetine hydrochloride and Cephaeline Hydrochloride.
The raw medicinal material ipecac that the present invention extracts from ipecac in the method for refining emetine hydrochloride and Cephaeline Hydrochloride is made up of madder wort Cephaelis acuminate Karsten or C.ipecacuanha (Brotero) A.Richard rhizome and root.
Adopt the present invention from ipecac, to extract the five batches of emetine hydrochlorides of method continuous production and the Cephaeline Hydrochloride of refining emetine hydrochloride and Cephaeline Hydrochloride, purity is all above 98%, and detailed results is seen table 1
The continuous five batches of purity of producing emetine hydrochloride and Cephaeline Hydrochloride of table 1
| Lot number | Emetine hydrochloride content % | Cephaeline Hydrochloride content % |
| 20120201 | 99.78 | 98.02 |
| 20120202 | 98.56 | 9800 |
| 20120301 | 98.35 | 98.13 |
| 20120302 | 99.20 | 98.23 |
| 20120303 | 98.99 | 98.11 |
Table 2 is made reference substance by oneself and is bought the reference substance parameter relatively
With available from U.S. Sigma company (lot number: emetine hydrochloride 061M1826V) and available from International Laboratory USA (lot number: 325166) Cephaeline Hydrochloride contrasts, and obtains spectrogram, sees Fig. 1-Fig. 4.
Process for purification of the present invention can be used for the refining preparation of standard substance, also can be used for the technology of suitability for industrialized production, produces purity 98% above emetine hydrochloride and Cephaeline Hydrochloride.Purity is apparently higher than the import standard substance.Adopt present method purification emetine hydrochloride and Cephaeline Hydrochloride; Have the advantages that technology is simple, be convenient to operate, and its purifying process stable and controllable, and lyophilized products is a powdery; Can directly use as bulk drug; Also can directly use, also have moulding simple, the advantage that stability is high even process other preparation as standard substance.
Description of drawings:
Fig. 1 Cephaeline Hydrochloride reference substance spectrogram
Fig. 2 makes the Cephaeline Hydrochloride spectrogram by oneself
Fig. 3 emetine hydrochloride reference substance spectrogram
Fig. 4 makes the emetine hydrochloride spectrogram by oneself
Embodiment
Following embodiment is used for illustrating the present invention and extracts the method made from extra care emetine hydrochloride and Cephaeline Hydrochloride from ipecac, but it can not constitute any restriction to scope of the present invention.
Embodiment 1:
One, extraction separation
1, instrument and material: ultrasonic extraction device: preparation HPLC:LC-8A preparative scale chromatography appearance, SPD-M10A detector (day island proper Tianjin); Rotary Evaporators RE-3000 (Shanghai Yarong Biochemical Instrument Plant); Freeze Drying Equipment ALPHA 1-4LD (German christ).
Medicinal material: ipecac, originate from Costa Rica, pulverize, cross sieve No. 3.
2, extract total alkaloids
A, get and pulverize back medicinal material 10g, add 200ml70% acidic ethanol (adding 2mlHCL in 70% ethanol), supersound extraction 1 hour;
B, extracting solution are centrifugal, get supernatant, and most ethanol is waved in 40 ℃ of decompressions of Rotary Evaporators, is concentrated into 50ml, adds ammonia solution adjust pH to 10;
C, with extracted with diethyl ether 4 times, each 50ml collects ether layer, water-bath volatilizes solvent, residue with the acetonitrile constant volume to the 10ml measuring bottle, subsequent use.
3, purifies and separates
Preparative hplc: LC-8A preparative scale chromatography appearance, SPD-M10A detector (day island proper Tianjin)
Chromatographic column: SunFire Prep C
1810 * 250mm, 5 μ m (U.S. waters company)
Chromatographic condition: acetonitrile: 0.05% triethylamine (45: 55), detect wavelength: 283nm
Flow velocity is: 5.0ml/min
In this system, the chromatographic peak about color atlas 13min is the Cephaeline Hydrochloride compound, directly with behind its fraction collection, is evaporated to after organic solvent removes, and carries out freeze-drying.Add a small amount of Hydrogen chloride, adjustment pH value 4 is carried out lyophilize.Earlier-40 degree pre-freezes after 4 hours, last Freeze Drying Equipment ,-50 spend freeze-drying 24 hours after drying 6 hours again, obtain Cephaeline Hydrochloride.
In this system, the chromatographic peak about color atlas 24min is the emetine hydrochloride compound, directly with behind its fraction collection, is evaporated to after organic solvent removes, and adds a small amount of Hydrogen chloride, and adjustment pH value 4 is carried out lyophilize.Earlier-40 degree pre-freezes after 4 hours, last Freeze Drying Equipment ,-50 spend freeze-drying 24 hours after drying 6 hours again, obtain emetine hydrochloride.
Embodiment 2:
One, extraction separation
1, instrument and material: ultrasonic extraction device; Preparation liquid phase: U.S. Waters 2535 detectors: 2489 UV-detectors; Rotary Evaporators RE-3000 (Shanghai Yarong Biochemical Instrument Plant); Freeze Drying Equipment ALPHA 1-4LD (German christ).
Medicinal material: ipecac, originate from Costa Rica, pulverize, cross sieve No. 2.
2, extract total alkaloids
A, get and pulverize back medicinal material 10g, add the acidic ethanol of 300ml 3%, alcohol concn is 90%, supersound extraction 2 hours;
B, extracting solution are centrifugal, get supernatant, and most ethanol is waved in 60 ℃ of decompressions of Rotary Evaporators, is concentrated into 30ml, adds ammonia solution adjust pH to 12;
C, with extracted with diethyl ether 3 times, each 30ml collects ether layer, water-bath volatilizes solvent, residue with the acetonitrile constant volume to the 10ml measuring bottle, subsequent use.
3, purifies and separates
Preparative hplc: preparation liquid phase: U.S. Waters 2535 detectors: 2489 UV-detector chromatographic columns: Agilent ZORBAX Eclipse XDB-C18 250mm*9.4mm*5um
Chromatographic condition: acetonitrile: 0.05% triethylamine (40: 60), detect wavelength: 283nm, flow velocity is: 1.0ml/min
In this system, the chromatographic peak about color atlas 35min is the Cephaeline Hydrochloride compound, directly with behind its fraction collection, is evaporated to after organic solvent removes, and carries out freeze-drying.Add a small amount of Hydrogen chloride, adjustment pH value 5 is carried out lyophilize.Earlier-40 degree pre-freezes after 4 hours, last Freeze Drying Equipment ,-50 spend freeze-drying 24 hours after drying 6 hours again, obtain Cephaeline Hydrochloride.
In this system, the chromatographic peak about color atlas 44min is the emetine hydrochloride compound, directly with behind its fraction collection, is evaporated to after organic solvent removes, and adds a small amount of Hydrogen chloride, and adjustment pH value 5 is carried out lyophilize.Earlier-40 degree pre-freezes after 4 hours, last Freeze Drying Equipment ,-50 spend freeze-drying 24 hours after drying 6 hours again, obtain emetine hydrochloride.
Embodiment 3:
One, extraction separation
1, instrument and material: ultrasonic extraction device; Preparation liquid phase: U.S. varian 940 LC detector: Prostar 325 UV-detectors; Rotary Evaporators RE-3000 (Shanghai Yarong Biochemical Instrument Plant); Freeze Drying Equipment ALPHA 1-4LD (German christ).
Medicinal material: ipecac, originate from Costa Rica, pulverize, cross sieve No. 3.
2, extract total alkaloids
A, get and pulverize back medicinal material 10g, add 100ml 2% acidic ethanol, alcohol concn is 60%, supersound extraction 0.5 hour;
B, extracting solution are centrifugal, get supernatant, and most ethanol is waved in 50 ℃ of decompressions of Rotary Evaporators, is concentrated into 40ml, adds ammonia solution adjust pH to 11;
C, with extracted with diethyl ether 3 times, each 40ml collects ether layer, water-bath volatilizes solvent, residue with the acetonitrile constant volume to the 10ml measuring bottle, subsequent use.
3, purifies and separates
Preparative hplc: U.S. varian 940LC detector: Prostar 325 UV-detectors;
Chromatographic column: Tianjin, island shjm-pack prep-ODS C1810 * 250mm 5 μ m
Chromatographic condition: acetonitrile: 0.05% triethylamine (50: 50), detect wavelength: 283nm, flow velocity is: 3.0ml/min
In this system, the chromatographic peak about color atlas 24min is the Cephaeline Hydrochloride compound, directly with behind its fraction collection, is evaporated to after organic solvent removes, and carries out freeze-drying.Add a small amount of Hydrogen chloride, adjustment pH value 5 is carried out lyophilize.Earlier-40 degree pre-freezes after 4 hours, last Freeze Drying Equipment ,-50 spend freeze-drying 24 hours after drying 6 hours again, obtain Cephaeline Hydrochloride.
In this system, the chromatographic peak about color atlas 32min is the emetine hydrochloride compound, directly with behind its fraction collection, is evaporated to after organic solvent removes, and adds a small amount of Hydrogen chloride, and adjustment pH value 5 is carried out lyophilize.Earlier-40 degree pre-freezes after 4 hours, last Freeze Drying Equipment ,-50 spend freeze-drying 24 hours after drying 6 hours again, obtain emetine hydrochloride.
Embodiment 4:
One, extraction separation
1, instrument and material: ultrasonic extraction device: preparation HPLC:LC-8A preparative scale chromatography appearance, SPD-M10A detector (day island proper Tianjin); Rotary Evaporators RE-3000 (Shanghai Yarong Biochemical Instrument Plant); Freeze Drying Equipment ALPHA 1-4LD (German christ).
Medicinal material: ipecac, originate from Costa Rica, pulverize, cross sieve No. 4.
2, extract total alkaloids
A, get and pulverize back medicinal material 10g, add 400ml 3% acidic ethanol, alcohol concn is 50%, supersound extraction 1.5 hours;
B, extracting solution are centrifugal, get supernatant, and most ethanol is waved in 60 ℃ of decompressions of Rotary Evaporators, is concentrated into 200ml, adds ammonia solution adjust pH to 10;
C, with extracted with diethyl ether 2 times, each 200ml collects ether layer, water-bath volatilizes solvent, residue with the acetonitrile constant volume to the 10ml measuring bottle, subsequent use.
3, purifies and separates
Preparative hplc: LC-8A preparative scale chromatography appearance, SPD-M10A detector (day island proper Tianjin) chromatographic column: SunFire Prep C
1810 * 250mm, 5 μ m (U.S. waters company)
Chromatographic condition: acetonitrile: 0.05% triethylamine (45: 55), detect wavelength: 285nm, flow velocity is: 5.0ml/min
In this system, the chromatographic peak about color atlas 18min is the Cephaeline Hydrochloride compound, directly with behind its fraction collection, is evaporated to after organic solvent removes, and carries out freeze-drying.Add a small amount of Hydrogen chloride, adjustment pH value 5 is carried out lyophilize.Earlier-40 degree pre-freezes after 4 hours, last Freeze Drying Equipment ,-50 spend freeze-drying 24 hours after drying 6 hours again, obtain Cephaeline Hydrochloride.
In this system, the chromatographic peak about color atlas 24min is the emetine hydrochloride compound, directly with behind its fraction collection, is evaporated to after organic solvent removes, and adds a small amount of Hydrogen chloride, and adjustment pH value 5 is carried out lyophilize.Earlier-40 degree pre-freezes after 4 hours, last Freeze Drying Equipment ,-50 spend freeze-drying 24 hours after drying 6 hours again, obtain emetine hydrochloride.
Claims (8)
1. one kind is extracted the method made from extra care emetine hydrochloride and Cephaeline Hydrochloride from ipecac, and this method comprises the steps:
A, supersound extraction: get the ipecac medicinal material, pulverize, add acidic ethanol, supersound extraction gets extracting solution A;
B, concentrated: extracting solution A is centrifugal, gets supernatant, waves most solvent, regulates pH value to alkalescence, gets liquid concentrator B;
C, extraction: liquid concentrator B collects ether layer with extracted with diethyl ether, volatilizes solvent, gets residue C;
D, separation and purification: with residue C dissolving, inject the preparation liquid phase, adopt preparative hplc to carry out separation and purification, adopt the ODS post to separate, moving phase is acetonitrile: triethylamine; According to detecting the corresponding bands of a spectrum of collection of illustrative plates emetine hydrochloride and Cephaeline Hydrochloride, fraction collection solution D and solution E respectively;
E, lyophilize: after the solution D that obtains and solution E be concentrated into organic solvent respectively and remove, regulate pH value, carry out lyophilize, obtain emetine hydrochloride and Cephaeline Hydrochloride to acid.
2. the method for from ipecac, extracting refining emetine hydrochloride and Cephaeline Hydrochloride according to claim 1, this method comprises the steps:
A, supersound extraction: get the ipecac medicinal material, pulverize, add the acidic ethanol that 10-40 doubly measures 1%-3%, alcohol concn is 50-90%, supersound extraction 0.5-2 hour, gets extracting solution A;
B, concentrated: extracting solution A is centrifugal, gets supernatant, and most ethanol is waved in 40-60 ℃ of decompression, regulates pH value to 10-12, gets liquid concentrator B;
C, extraction: liquid concentrator B collects ether layer with volume extracted with diethyl ether 1-4 time, volatilizes solvent, residue C;
D, separation and purification: C dissolves with acetonitrile with residue, is settled to be equivalent to the every ml of crude drug amount 1g, adopts preparative hplc to carry out separation and purification, chromatographic condition: chromatographic column: ODS chromatographic column; Moving phase is acetonitrile: 0.05% triethylamine, room temperature volume ratio are 40-45: 60-55; Flow velocity is 1.0ml/min-5.0ml/min; According to detecting the corresponding bands of a spectrum of collection of illustrative plates emetine hydrochloride and Cephaeline Hydrochloride, fraction collection solution D and solution E respectively;
E, lyophilize: the solution D that obtains and solution E are evaporated to respectively after organic solvent removes, and adjustment pH value is carried out lyophilize to 3-5, obtains emetine hydrochloride and Cephaeline Hydrochloride.
3. the method for from ipecac, extracting refining emetine hydrochloride and Cephaeline Hydrochloride according to claim 1, this method comprises the steps:
A, supersound extraction: get the ipecac medicinal material, pulverize, add the acidic ethanol of 20 times of amounts 1%, alcohol concn is 70%, and supersound extraction 1 hour gets extracting solution A;
B, concentrated: extracting solution A is centrifugal, gets supernatant, and most ethanol is waved in 40 ℃ of decompressions, regulates pH value to 10, gets liquid concentrator B;
C, extraction: liquid concentrator B collects ether layer with the extracted with diethyl ether of same volume 4 times, volatilizes solvent, residue C;
D, separation and purification: C dissolves with acetonitrile with residue, is settled to be equivalent to the every ml of crude drug amount 1g, adopts preparative hplc to carry out separation and purification, chromatographic condition: chromatographic column: C
18Chromatographic column; Moving phase is acetonitrile: 0.05% triethylamine, room temperature volume ratio are 45: 55; Flow velocity is 5.0ml/min; According to detecting the corresponding bands of a spectrum of collection of illustrative plates emetine hydrochloride and Cephaeline Hydrochloride, fraction collection solution D and solution E respectively;
E, lyophilize: the solution D that obtains and solution E are evaporated to respectively after organic solvent removes, and adjustment pH value to 4 is carried out lyophilize, obtains emetine hydrochloride and Cephaeline Hydrochloride.
4. the method for from ipecac, extracting refining emetine hydrochloride and Cephaeline Hydrochloride according to claim 1 is characterized in that this method comprises the steps:
A, supersound extraction: get the ipecac medicinal material, pulverize, add the acidic ethanol of 30 times of amounts 3%, alcohol concn is 90%, and supersound extraction 2 hours gets extracting solution A;
B, concentrated: extracting solution A is centrifugal, gets supernatant, and most ethanol is waved in 60 ℃ of decompressions, regulates pH value to 12, gets liquid concentrator B;
C, extraction: liquid concentrator B collects ether layer with the extracted with diethyl ether of same volume 1 time, volatilizes solvent, residue C;
D, separation and purification: C dissolves with acetonitrile with residue, is settled to be equivalent to the every ml of crude drug amount 1g, adopts preparative hplc to carry out separation and purification, chromatographic condition: chromatographic column: C
18Chromatographic column; Moving phase is acetonitrile: 0.05% triethylamine, room temperature volume ratio are 40: 60; Flow velocity is 1.0ml/min; According to detecting the corresponding bands of a spectrum of collection of illustrative plates emetine hydrochloride and Cephaeline Hydrochloride, fraction collection solution D and solution E respectively;
E, lyophilize: the solution D that obtains and solution E are evaporated to respectively after organic solvent removes, add a small amount of Hydrogen chloride, adjustment pH value to 5 is carried out lyophilize, obtains emetine hydrochloride and Cephaeline Hydrochloride.
5. the method for from ipecac, extracting refining emetine hydrochloride and Cephaeline Hydrochloride according to claim 1 is characterized in that this method comprises the steps:
A, supersound extraction: get the ipecac medicinal material, pulverize, add the acidic ethanol of 10 times of amounts 2%, alcohol concn is 60%, and supersound extraction 0.5 hour gets extracting solution A;
B, concentrated: extracting solution A is centrifugal, gets supernatant, and most ethanol is waved in 50 ℃ of decompressions, regulates pH value to 11, gets liquid concentrator B;
C, extraction: liquid concentrator B collects ether layer with the extracted with diethyl ether of same volume 3 times, volatilizes solvent, residue C;
D, separation and purification: C dissolves with acetonitrile with residue, is settled to be equivalent to the every ml of crude drug amount 1g, adopts preparative hplc to carry out separation and purification, chromatographic condition: chromatographic column: C
18Chromatographic column; Moving phase is acetonitrile: 0.05% triethylamine, room temperature volume ratio are 40: 60; Flow velocity is 3.0ml/min; According to detecting the corresponding bands of a spectrum of collection of illustrative plates emetine hydrochloride and Cephaeline Hydrochloride, fraction collection solution D and solution E respectively;
E, lyophilize: the solution D that obtains and solution E are evaporated to respectively after organic solvent removes, add a small amount of Hydrogen chloride, adjustment pH value to 3 is carried out lyophilize, obtains emetine hydrochloride and Cephaeline Hydrochloride.
6. the method for from ipecac, extracting refining emetine hydrochloride and Cephaeline Hydrochloride according to claim 1 is characterized in that this method comprises the steps:
A, supersound extraction: get the ipecac medicinal material, pulverize, add the acidic ethanol of 40 times of amounts 3%, alcohol concn is 50%, and supersound extraction 1.5 hours gets extracting solution A;
B, concentrated: extracting solution A is centrifugal, gets supernatant, and most ethanol is waved in 60 ℃ of decompressions, regulates pH value to 10, gets liquid concentrator B;
C, extraction: liquid concentrator B collects ether layer with volume extracted with diethyl ether 2 times, volatilizes solvent, residue C;
D, separation and purification: C dissolves with acetonitrile with residue, is settled to be equivalent to the every ml of crude drug amount 1g, adopts preparative hplc to carry out separation and purification, chromatographic condition: chromatographic column: C
18Chromatographic column; Moving phase is acetonitrile: 0.05% triethylamine, room temperature volume ratio are 45: 55; Flow velocity is 4.0ml/min; According to detecting the corresponding bands of a spectrum of collection of illustrative plates emetine hydrochloride and Cephaeline Hydrochloride, fraction collection solution D and solution E respectively;
E, lyophilize: the solution D that obtains and solution E are evaporated to respectively after organic solvent removes, and adjustment pH value to 5 is carried out lyophilize, obtains emetine hydrochloride and Cephaeline Hydrochloride.
7. according to the arbitrary described method of from ipecac, extracting refining emetine hydrochloride and Cephaeline Hydrochloride of claim 1-6, it is characterized in that adjustment of acidity is used hydrochloric acid, regulate alkalescence and use ammonia solution.
8. according to the arbitrary described method of from ipecac, extracting refining emetine hydrochloride and Cephaeline Hydrochloride of claim 1-6, it is characterized in that in the steps d, detecting wavelength in the chromatographic condition is 283nm.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106421013A (en) * | 2016-08-30 | 2017-02-22 | 山东百维药业有限公司 | Extracting method of radix ipecacuanhae extract |
| WO2017067366A1 (en) * | 2015-10-22 | 2017-04-27 | 成都瑞芬思生物科技有限公司 | Method for extracting and refining alkaloid from ipecac |
| CN109662965A (en) * | 2019-01-31 | 2019-04-23 | 吉林大学 | Application of the Cephaeline Hydrochloride in preparation treatment neuroglia tumor medicine |
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|---|---|---|---|---|
| WO1995001984A1 (en) * | 1993-07-06 | 1995-01-19 | Polis A.G. | Process for the extraction and purification of alkaloids |
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| WO1995001984A1 (en) * | 1993-07-06 | 1995-01-19 | Polis A.G. | Process for the extraction and purification of alkaloids |
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| 许立颖等: "吐根醚溶性生物碱提取工艺研究", 《制剂与技术》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017067366A1 (en) * | 2015-10-22 | 2017-04-27 | 成都瑞芬思生物科技有限公司 | Method for extracting and refining alkaloid from ipecac |
| US10258661B2 (en) | 2015-10-22 | 2019-04-16 | Chengdu Herbpurify Co., Ltd. | Method for extracting and refining alkaloids from ipecac |
| CN106421013A (en) * | 2016-08-30 | 2017-02-22 | 山东百维药业有限公司 | Extracting method of radix ipecacuanhae extract |
| CN109662965A (en) * | 2019-01-31 | 2019-04-23 | 吉林大学 | Application of the Cephaeline Hydrochloride in preparation treatment neuroglia tumor medicine |
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Effective date of registration: 20151110 Address after: 055550 Xingtai City, Cao Zhuang management area, Hebei Patentee after: Jing Jing Pharmaceutical Co., Ltd. Address before: 050035 Shijiazhuang high tech Development Zone, Hebei Province, Tianshan Road, No. 238 Patentee before: Song Jian |