CN101054377B - Total alkaloids extraction of corydalis, its preparation method, medicine composition containing the total alkaloids extraction and application thereof - Google Patents

Total alkaloids extraction of corydalis, its preparation method, medicine composition containing the total alkaloids extraction and application thereof Download PDF

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Publication number
CN101054377B
CN101054377B CN200610025704A CN200610025704A CN101054377B CN 101054377 B CN101054377 B CN 101054377B CN 200610025704 A CN200610025704 A CN 200610025704A CN 200610025704 A CN200610025704 A CN 200610025704A CN 101054377 B CN101054377 B CN 101054377B
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corydalis
rhizome
extract
total alkaloid
acid
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CN101054377A (en
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蒋爱芳
杨义芳
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Shanghai Institute of Pharmaceutical Industry
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Shanghai Institute of Pharmaceutical Industry
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Abstract

The present invention discloses a Rhizoma Corydalis Decumbentis total alkaloids extract, its preparation method, pharmaceutical composition containing same. The total alkaloids mainly comprise : macleyine, tetrahydropalmatine, bicucalline, palmatine hydrochloride, 'xiawuning' alkaloid, corydaline harmine, other alkaloid and extract. The preparation method is : using Rhizoma Corydalis Decumbentis as material, adding right amount of polar solvent for leaching, merging the leachate, carrying out large pore adsorption resin chromatography, eluting impurity with diluted acid and alkaline aqueous solution orderly, eluting using polar organic solvent, collecting elution liquor, eliminating impurity further by alumina column adsorption, Collecting after-column liquid, concentrating liquor to obtain the Rhizoma Corydalis Decumbentis total alkaloids extract. The present invention also discloses a pharmaceutical composition containing the total alkaloids extract and uses of the pharmaceutical composition in preparing tablet, capsule, soft capsule, suppository, granula, transdermal absorption agent, drop pills, oral disintegrating agent, slow release agent, freeze-drying powder injection etc.

Description

Total alkaloid of corydalis rhizome extract, its preparation method, the pharmaceutical composition that contains this total alkaloids extract and application thereof
Technical field
The present invention relates to traditional field of Chinese herbal, be specifically related to total alkaloid of corydalis rhizome, its preparation method, contain the pharmaceutical composition of total alkaloid of corydalis rhizome, and the application of this pharmaceutical composition in pharmaceutical preparation.
Background technology
Rhizome of Decumbent Corydalis is dry tuber or the herb of papaveracease Corydalis plant Hotseason grow Corydalis decumbens (Thunb.) Pers., Rhizome of Decumbent Corydalis is distributed widely in provinces such as Jiangsu, Anhui, Zhejiang, Jiangxi, Fujian, Taiwan, Hunan, be China's herbal medicine commonly used, effects such as tool is invigorated blood circulation, vein relaxing, promoting the circulation of qi, pain relieving.Cure mainly the stroke hemiplegia that hypertension, the cerebrovascular cause, and rheumatic arthritis, sciatica, poliomyelitis sequela etc. are had better action.Its main effective constituent is the iloquinoline derivative total alkaloids.From the seventies, scholar both domestic and external has just carried out comparatively systematic research and discussion to chemical ingredients, pharmacologically active, crude drug and the place of production situation of this medicine.The research of Chemical Constituents of Corydalis separated up to now obtained more than 30 isoquinoline alkaloid, mainly contain protopine (protopine), tetrahydropalmatine (tetrahydropalmatine), finish withered spirit (bicuculline), palmatine alkaloids such as (palmatine), nearly all belong to the benzylisoquinoline class, wherein benzene peptidyl isoquinoline 99.9/tetrahydroisoquinoline (phthalideisoquinoline/tetrahydroisoquinoline) is than unique biological alkali, totally 11.
At present, the method for Rhizome of Decumbent Corydalis preparation extract total alkaloids is a lot, in recent years researched and proposed many patent innovative technologies.
The Gu Zhenlun of Suzhou Chinese Herbal Medicine Inst etc. has invented the extracting method of total alkaloid of corydalis rhizome, adopt acid carry-technologies such as resin absorption make with extra care extract, make total alkaloids purity be about 70-90%, and wherein the content of protopine account for more than 50% of total alkaloids.Investigate from the source of students angle, we too much criticize, the composition analysis of different year Rhizome of Decumbent Corydalis crude drug total alkaloids, and it is 20-30% that protopine accounts for total alkaloid content.This method adopts diluted acid to decoct repeatedly, and condition is acute, impels some alkaloid to take place to transform or destroyed possibly; Moreover this technology is power consumption, requires also higher to equipment and materials; Use sour molten alkali precipitation at last, the significant part of water-soluble quaternary ammonium hydroxide is removed (publication number: CN 1445227A).
The vast stretch of wooded country of Hunan Province's institute of Pharmaceutical Industry etc. has been invented total alkaloid of corydalis rhizome and preparation method thereof, adopts the general technology of diluted acid diacolation, and this is that Rhizome of Decumbent Corydalis Jiangxi standard is in the promptly disclosed technology of the seventies in last century; Then and the diluted acid percolate, after steps such as macroporous adsorbent resin removal of impurities, also need at last with steps such as alkali precipitations, the same with aforesaid method exist extracts active ingredients not exclusively and method too numerous and diverse, make shortcoming (publication numbers: CN 1535969A) such as rate of transform reduction.
Jiangxi Province's Mao Youchang has proposed the patent application (publication number: CN 1456153A) that total alkaloid of corydalis rhizome is used to prepare preparations such as Rhizoma Corydalis Decumbentis tablet, capsule, freeze-dried powder.CN 1557413A) and preparation (publication number: patent application CN 1557414A) such as oral cavity quick disintegrating slice Tianshikang Science ﹠ Technology Development Co., Ltd., Jiangxi Prov has proposed that Rhizome of Decumbent Corydalis is slow, controlled release preparation (publication number:.Above-mentioned two total alkaloid of corydalis rhizome that patent is related have all adopted the extracting method of Jiangxi Province's drug standard (nineteen eighty-twos), and its active constituent content is low, and impurity is many, has influenced curative effect of medication.
At present, commercially available Rhizome of Decumbent Corydalis preparation comprises Rhizome of Decumbent Corydalis tablet, Rhizoma Corydalis Decumbentis Injection and Guttae Rhizoma Corydalis Decumbentis etc. the Rhizome of Decumbent Corydalis preparation still has very big deficiency in clinical application, it is big and store shortcoming such as inconvenience to have dosage as Rhizoma Corydalis Decumbentis tablet; Injection liquid needs frequent injection, bring very big inconvenience to patient. in recent years, also the someone has carried out the exploitation and the research of Rhizome of Decumbent Corydalis capsule and oral liquid, its analgesic activity all is better than the Rhizome of Decumbent Corydalis tablet. and we consider the diversity of total alkaloid of corydalis rhizome pharmacologically active, and it is lower effectively to treat concentration, being fit to be developed into multiple novel modern formulation is applied to clinical. and the inventor is based on the experience of being engaged in modernization of cmm for a long time, at first major tuneup the separation and the extracting method of Chinese medicine total alkaloid of corydalis rhizome, and further study on this basis and proposed total alkaloid of corydalis rhizome and can make tablet, capsule, soft capsule, suppository, granule, transdermal, dripping pill, oral rapidly disintegrating formulation, sustained-release preparation, the application of novel pharmaceutical formulations such as freeze-dried powder, thus the present invention finished.
The extraction process dry technology that the present invention relates to has adopted drying under reduced pressure or spray drying technology; The corydalis decumbentis orally rapidly disintegrating formulation has adopted inclusion technique and spray drying technology, and the Rhizoma corydalis decumbentis total alkaloids freeze-dried powder has adopted Freeze Drying Technique, has improved the quality of preparation.
Summary of the invention
The technical problem to be solved in the present invention is, deficiency at above-mentioned each patented technology, set up the more total alkaloid of corydalis rhizome extracting method of scientific and efficient, its preparation method is with the raw material of doing nothing summer, adds an amount of polar solvent diacolation and extracts, percolate is directly through macroporous adsorption resin chromatography, with diluted acid and dilute alkaline soln wash-out removal of impurities successively, again with the polar organic solvent wash-out, elutriant adsorbs further removal of impurities through alumina column again, collect liquid behind the post, concentrate the Rhizoma corydalis decumbentis total alkaloids extract.
The total alkaloid of corydalis rhizome extract that to the invention provides a kind of dry tuber with papaveracease Corydalis plant Hotseason grow (Rhizome of Decumbent Corydalis) be feedstock production, wherein alkaloidal weight percent is formed and is comprised:
Protopine: 20~30%
Tetrahydropalmatine: 15~25%
Finish withered spirit: 10~15%
Palmatine hydrochloride: 5~10%
Summer is alkali rather: 10~15%
You are bright for corydalis: 5~10%
Other biological alkali and extract: 5~20%
Its total alkaloid content is measured with UV method or HPLC method and is no less than 85%.
The present invention also provides the method for the described total alkaloid of corydalis rhizome extract of preparation, the steps include:
(1) dry tuber of bloodroot Hotseason grow (Rhizome of Decumbent Corydalis) is a raw material, the aqueous acid that adds 2~3 times of this crude drug in whole raw material weights soaked after 12~36 hours, the aqueous acid that continues with 5~20 times carries out the diacolation extraction, 1~3 day extraction time, collect percolate to the lifeless matter alkali reaction, merge percolate;
It is a kind of in 0.01~10% phosphoric acid, hydrochloric acid, sulfuric acid, the aqueous acetic acid that described aqueous acid is selected from concentration; Preferred concentration 0.05~8%, more preferably concentration 0.1~5%, most preferable concentrations 0.2~2%.
(2) with step (1) gained percolate with absorption with macroporous adsorbent resin, remove impurity towards post successively with 1~5 times diluted acid and dilute alkaline aqueous solution respectively then;
It is a kind of in 0.01~10% phosphoric acid, hydrochloric acid, sulfuric acid, the aqueous acetic acid that described diluted acid is selected from concentration, preferred concentration 0.05~8%, and more preferably concentration 0.1~5%, most preferable concentrations 0.2~2%; It is a kind of in 0.01~15% potassium hydroxide, sodium hydroxide, the ammonia aqueous solution that described diluted alkaline is selected from concentration, preferred concentration 0.05~10%, and more preferably concentration 0.1~8%, most preferable concentrations 0.5~5%.
Described macroporous adsorbent resin is selected from a kind of among AL-1, AL-2, D-101, DA-201, DM-301, ADS-5, ADS-8, ME-1, ME-2, the AB-8, be preferably selected from a kind of among AL-1, AL-2, D-101, DA-201, DM-301, ME-1, ME-2, the AB-8, more preferably be selected from a kind of among D-101, DA-201, DM-301, ME-1, ME-2, the AB-8, most preferably be selected from a kind of among D-101, DA-201, ME-1, ME-2, the AB-8.
(3) with the macroporous adsorptive resins of step (2) high concentration ethanol wash-out, collect elutriant with 5~20 times;
Described high concentration ethanol is that concentration is 〉=50% ethanol, is preferably concentration to be 〉=60% ethanol.
(4) with step (3) gained elutriant again through alumina column absorption (aluminum oxide use in advance high concentration ethanol wetting saturated), liquid behind the post is collected in further removal of impurities, concentrate the Rhizoma corydalis decumbentis total alkaloids extract;
Described aluminum oxide is neutral alumina or alkali alumina, and its granularity is 100~300 orders.
Described high concentration ethanol is the ethanol of concentration 〉=50%, is preferably concentration to be 〉=60% ethanol.
The content of gained total alkaloid of corydalis rhizome is measured with UV or HPLC method and is no less than 85%.
The present invention also provides a kind of pharmaceutical composition that comprises described total alkaloid of corydalis rhizome extract, and the application of this pharmaceutical composition on useful in preparing drug formulations.
Described pharmaceutical preparation comprises tablet, capsule, soft capsule, suppository, granule, transdermal absorption formulation, dripping pill, oral rapidly disintegrating formulation, sustained-release preparation, lyophilized injectable powder etc.
The thin-layer chromatography result shows, comprise in the total alkaloid of corydalis rhizome by the inventive method preparation but be not only limited to the summer rather alkali (you are bright for (+)-egenine), corydalis ((+)-kikemanine), protopine (protopine), finishes withered clever alkali (bicuculline), tetrahydropalmatine (tetrahydropalmatine) and palmatine multiple alkaloids such as (palmatine).
Preparation method of the present invention is efficient, simple and easy to do, and its total alkali rate of transform reaches more than 90%, and purity is greater than 85%; Adopt finger printing to analyze and quality control, carry out chemical fingerprint with drug effect finger printing dependency is got in touch research, the ratio of regulation component is measured its weight percent to accounting for the chemical ingredients employing HPLC method of total alkaloids more than 90%.
Rhizoma corydalis decumbentis total alkaloids pharmaceutical composition of the present invention contains multiple alkaloid, and the clear and definite weight percent of each composition, more meets the natural ratio that exists of each composition in the decumbent corydalis as medicine material source of students, its pharmacological effect of performance that can be safer and more effective.The data in nearly ten years is investigated and is found, generally all is the pharmacological effect research of carrying out at total alkaloid of corydalis rhizome, and general Shandong tropine only is the effective monomer that wherein easy extraction separation obtains, and Rhizome of Decumbent Corydalis generally is to be that efficient part is used as medicine with the total alkali.
Pharmaceutical composition of the present invention is owing to have this alkaloidal component and the content identical with the medicinal material source of students, and the high purity total alkaloids, makes to have incomparable advantage compared to existing technology aspect the preparation making.The related total alkaloid of corydalis rhizome of patent application of prior art CN 1456153A and CN 1557413A and CN 1557414A, all adopted the extracting method of Jiangxi Province's drug standard (nineteen eighty-twos), its active constituent content is low, impurity is many, influenced curative effect of medication, also be difficult to simultaneously to accomplish the preparation that conforms to quality requirements, especially as freeze-dried powder, slow, controlled release preparation, oral rapidly disintegrating formulation.The extraction process dry technology that the present invention relates to has adopted drying under reduced pressure or spray drying technology; The corydalis decumbentis orally rapidly disintegrating formulation has adopted inclusion technique and spray drying technology, and the Rhizoma corydalis decumbentis total alkaloids freeze-dried powder has adopted Freeze Drying Technique, has improved the quality of preparation.
Pharmaceutical composition of the present invention makes the quality stability of extraction process that guarantee arranged owing to have clear and definite like this component and content, and as the medicine of preventing and curing diseases, this point is particularly important.
As known from the above, the invention provides the application of pharmaceutical composition in pharmaceutical preparation of total alkaloid of corydalis rhizome and preparation method thereof and described total alkaloids composition, they have overcome the defective of prior art, and have realized the controllability of total alkaloid of corydalis rhizome inner quality.
Description of drawings:
Fig. 1 and Fig. 2 are the finger printings that shows that total alkaloids effective constituent of the present invention exists, and wherein Fig. 1 is the thin-layer chromatogram of total alkaloid of corydalis rhizome, and Fig. 2 is high performance liquid chromatography (HPLC) fingerprint image.
The figure acceptance of the bid not expression of keeping the score: a-finishes withered spirit, and the b-summer is alkali rather, the c-protopine, and the d-total alkaloid of corydalis rhizome, the e-tetrahydropalmatine, f-corydalis that is bright, the g-palmatine hydrochloride; 1-finishes withered spirit, and the 2-summer is alkali rather, and you are bright for the 3-corydalis, 4-protopine, 5-tetrahydropalmatine, 6-palmatine hydrochloride.
Embodiment
Further specify the present invention below in conjunction with embodiment.It should be understood that embodiments of the invention are to be used to illustrate the present invention rather than limitation of the present invention.Under the prerequisite of the spirit and principles in the present invention, all belong to the scope of protection of present invention to inventing any change that indivedual technological steps carry out and changing.In the present invention, the percentage composition of each composition in extract is under chromatographic condition, by the external standard two-point method, utilizes the peak area value of corresponding composition in reference substance and the extract to calculate gained.In addition, (v/v) expression volume by volume concentration or volume ratio; (w/w) expression weight ratio concentration or weight ratio.Except as otherwise noted, percentage ratio of the present invention is weight percentage, and removing other has regulation, and the total alkaloid of corydalis rhizome extract that the present invention uses embodiment 1 to prepare carries out formulation preparation.
Embodiment 1: a kind of preparation method of total alkaloid of corydalis rhizome
Get 1 kilogram of Rhizome of Decumbent Corydalis crude drug meal, add 3 liters of soaked overnight of hydrochloric acid soln of 1% (v/v), insert in 50 liters of percolators,, collect percolate to alkaloid and react till the reaction that is negative with the above-mentioned solution diacolation of 1% (v/v).Collect about 12 liters altogether of percolates.Per 100 milliliters of percolates amount to the crude drug amount 8.33 grams approximately.
Get percolate, last column volume is 2000 milliliters macroporous adsorbent resin D-101; Hydrochloric acid soln washing with 1~2 times of column volume 1% (v/v); Use the aqueous sodium hydroxide washes of 10% (w/w) to take off to look shallow again; Be washed till nearly neutrality with deionized water again; Again with the static wash-out of 75% ethanol and collect, get final product to elutriant lifeless matter alkali reaction; Elutriant is again through the absorption of 1000 milliliters alumina column (aluminum oxide use in advance high concentration ethanol wetting saturated), collects liquid behind the post, puts 70 ℃ of water-bath concentrating under reduced pressure dryings, that is, total alkaloid content is 85.7%.Its weight percent is formed and is comprised: protopine 27.9%, tetrahydropalmatine 17.8%, finish withered clever 14.2%, palmatine hydrochloride 8.6%, the summer is alkali 11.8% rather, you are bright 5.4% for corydalis, other biological alkali and extract 14.3%.
Embodiment 2: a kind of preparation method of total alkaloid of corydalis rhizome
Get 1 kilogram of Rhizome of Decumbent Corydalis crude drug meal, add 3 liters of soaked overnight of phosphoric acid solution of 10% (v/v), insert in 50 liters of percolators,, collect percolate to alkaloid and react till the reaction that is negative with the above-mentioned solution diacolation of 10% (v/v).Collect about 15 liters altogether of percolates.Per 100 milliliters of percolates amount to the crude drug amount 6.67 grams approximately.
Get percolate, last column volume is 2000 milliliters macroporous adsorbent resin ME-2; Phosphoric acid solution washing with 1~2 times of column volume 10% (v/v); Use the aqueous sodium hydroxide washes of 15% (w/w) to take off to look shallow again; Be washed till nearly neutrality with deionized water again; Again with the static wash-out of 95% ethanol and collect, get final product to elutriant lifeless matter alkali reaction; Elutriant is again through the absorption of 1000 milliliters alumina column (aluminum oxide use in advance high concentration ethanol wetting saturated), collects liquid behind the post, puts 70 ℃ of water-bath concentrating under reduced pressure dryings, that is, total alkaloid content is 83.2%.Its weight percent is formed and is comprised: protopine 21.7%, tetrahydropalmatine 19.9%, finish withered clever 13.8%, palmatine hydrochloride 5.6%, the summer is alkali 13.5% rather, you are bright 8.7% for corydalis, other biological alkali and extract 16.8%.
Embodiment 3: a kind of preparation method of total alkaloid of corydalis rhizome
Get 1 kilogram of Rhizome of Decumbent Corydalis crude drug meal, add 3 liters of soaked overnight of sulphuric acid soln of 0.01% (v/v), insert in 50 liters of percolators,, collect percolate to alkaloid and react till the reaction that is negative with the above-mentioned solution diacolation of 0.01% (v/v).Collect about 10 liters altogether of percolates.Per 100 milliliters of percolates amount to the crude drug amount 10 grams approximately.
Get percolate, last column volume is 2000 milliliters macroporous adsorbent resin D-101; Sulphuric acid soln washing with 1~2 times of column volume 0.01% (v/v); Use the aqueous sodium hydroxide washes of 0.05% (w/w) to take off to look shallow again; Be washed till nearly neutrality with deionized water again; Again with 60~95% ethanol dynamic desorption and collect, get final product to elutriant lifeless matter alkali reaction; Elutriant is again through the absorption of 1000 milliliters alumina column (aluminum oxide use in advance high concentration ethanol wetting saturated), collects liquid behind the post, puts 70 ℃ of water-bath concentrating under reduced pressure dryings, that is, total alkaloid content is 94.4%.Its weight percent is formed and is comprised: protopine 29.8%, tetrahydropalmatine 21.6%, finish withered clever 12.7%, palmatine hydrochloride 9.7%, the summer is alkali 10.8% rather, you are bright 9.8% for corydalis, other biological alkali and extract 5.6%.
Embodiment 4: a kind of preparation method of total alkaloid of corydalis rhizome
Get 1 kilogram of Rhizome of Decumbent Corydalis crude drug meal, add 3 liters of soaked overnight of hydrochloric acid soln of 4% (v/v), insert in 50 liters of percolators,, collect percolate to alkaloid and react till the reaction that is negative with the above-mentioned solution diacolation of 4% (v/v).Collect about 13 liters altogether of percolates.Per 100 milliliters of percolates amount to the crude drug amount 7.7 grams approximately.
Get percolate, last column volume is 2000 milliliters macroporous adsorbent resin AB-8; Hydrochloric acid soln washing with 1~2 times of column volume 4% (v/v); Use the aqueous sodium hydroxide washes of 1% (w/w) to take off to look shallow again; Be washed till nearly neutrality with deionized water again; Again with 60~95% ethanol dynamic desorption and collect, get final product to elutriant lifeless matter alkali reaction; Elutriant is again through the absorption of 1000 milliliters alumina column (aluminum oxide use in advance high concentration ethanol wetting saturated), collects liquid behind the post, puts 70 ℃ of water-bath concentrating under reduced pressure dryings, that is, total alkaloid content is 80.5%.Its weight percent is formed and is comprised: protopine 25.2%, tetrahydropalmatine 15.6%, finish withered clever 11.4%, palmatine hydrochloride 6.9%, the summer is alkali 14.9% rather, you are bright 6.5% for corydalis, other biological alkali and extract 19.5%.
Embodiment 5: a kind of preparation method of total alkaloid of corydalis rhizome
Get 1 kilogram of Rhizome of Decumbent Corydalis crude drug meal, add 3 liters of soaked overnight of acetum of 8% (v/v), insert in 50 liters of percolators,, collect percolate to alkaloid and react till the reaction that is negative with the above-mentioned solution diacolation of 5% (v/v).Collect about 13 liters altogether of percolates.Per 100 milliliters of percolates amount to the crude drug amount 7.7 grams approximately.
Get percolate, last column volume is 2000 milliliters macroporous adsorbent resin AB-8; Acetum washing with 1~2 times of column volume 5% (v/v); Use the aqueous sodium hydroxide washes of 5% (w/w) to take off to look shallow again; Be washed till nearly neutrality with deionized water again; Again with 60~95% ethanol dynamic desorption and collect, get final product to elutriant lifeless matter alkali reaction; Elutriant is again through the absorption of 1000 milliliters alumina column (aluminum oxide use in advance high concentration ethanol wetting saturated), collects liquid behind the post, puts 70 ℃ of water-bath concentrating under reduced pressure dryings, that is, total alkaloid content is 87.2%.Its weight percent is formed and is comprised: protopine 23.8%, tetrahydropalmatine 24.6%, finish withered clever 10.5%, palmatine hydrochloride 7.8%, the summer is alkali 12.6% rather, you are bright 7.9% for corydalis, other biological alkali and extract 12.8%.
Embodiment 6: a kind of preparation---the tablet of total alkaloid of corydalis rhizome
Total alkaloid of corydalis rhizome 5 grams
Magnesium Stearate 5 grams
Starch 90 grams
Make 1000
Promptly get the total alkaloid of corydalis rhizome oral tablet through technologies such as compressing tablet, dressing, bottlings according to a conventional method behind said components (total alkaloid of corydalis rhizome, Magnesium Stearate and the starch) mixing.
Embodiment 7: a kind of preparation of total alkaloid of corydalis rhizome---oral hard capsule agent
Total alkaloid of corydalis rhizome 5 grams
Dry starch 100 grams
Make 1000
1000 hard capsule of packing into behind said components (total alkaloid of corydalis rhizome and the dry starch) mixing granulation promptly get the agent of total alkaloid of corydalis rhizome oral hard capsule.
Embodiment 8: a kind of preparation---the soft capsule of total alkaloid of corydalis rhizome
Total alkaloid of corydalis rhizome 5 grams
PEG400 200 grams
Polyglycerol ester 10 grams
Make 1000
Total alkaloid of corydalis rhizome is ground into fine powder, adds PEG400 and polyglycerol ester and puts in the colloidal mill, disperses, and pressing is sealed in the soft capsule material after the even matter.Promptly.
Embodiment 9: a kind of preparation---the suppository of total alkaloid of corydalis rhizome
Total alkaloid of corydalis rhizome 5 grams
Semi-synthetic lipid acid is sweet an amount of
Grease
Make 1000
Get the heating of semi-synthetic fatty acid glycerine fat and make and melt, suitably the cooling back adds 5 gram total alkaloid of corydalis rhizome mixings, the system bolt, and cooling promptly gets total alkaloid of corydalis rhizome suppository.
Embodiment 10: a kind of preparation---the granule of total alkaloid of corydalis rhizome
Total alkaloid of corydalis rhizome 5 grams
Lactose 200 grams
Dextrin 795 grams
Make 500 bags
Said components is mixed the back granulation, is distributed into 500 bags.Promptly get the total alkaloid of corydalis rhizome oral granular formulation.
Embodiment 11: a kind of preparation---the transdermal absorption formulation of total alkaloid of corydalis rhizome
Total alkaloid of corydalis rhizome 5 grams
15% propylene glycol is an amount of
5% oleic acid is an amount of
1.5% azone is an amount of
Make 1000
Total alkaloid of corydalis rhizome is ground into fine powder; the mixing solutions that adds 15% propylene glycol, 5% oleic acid, 1.5% azone is an infiltration accelerating agent, and is an amount of, homogenate; be dissolved in the medical grade silicone pressure-sensitive adhesive; prepare each layer matrix, with back sheet, pastille pressure sensitive adhesive, the coating of each layer of protective layer, oven dry; each lamination closes; cut, packing, promptly.
Embodiment 12: a kind of preparation---the dripping pill of total alkaloid of corydalis rhizome
Total alkaloid of corydalis rhizome 5 grams
Polyoxyethylene glycol is an amount of
Make 1000
Total alkaloid of corydalis rhizome is ground into fine powder, and taking polyethylene glycol is an amount of, and heating makes fusion, adds the total alkaloid of corydalis rhizome fine powder, and mixing splashes in the refrigerative whiteruss, makes 1000 of dripping pills.
Embodiment 13: a kind of preparation of total alkaloid of corydalis rhizome---oral rapidly disintegrating formulation (tablet)
Total alkaloid of corydalis rhizome 7.5 grams
Beta-cyclodextrin 30 grams
Microcrystalline Cellulose 130 grams
Crosslinked polyethylene pyrroles 30 grams
Alkane ketone
Magnesium Stearate 1.5 grams
Stevioside 1 gram
Make 1000
The Rhizoma corydalis decumbentis total alkaloids superfine grinding gets 300 order fine powders, gets the recipe quantity beta-cyclodextrin and carries out inclusion, takes by weighing recipe quantity Microcrystalline Cellulose, cross-linked polyvinylpyrrolidone, Magnesium Stearate, stevioside mixing then, and low pressure is pressed into 1000.
Embodiment 14: a kind of preparation of total alkaloid of corydalis rhizome---sustained-release preparation (gel matrix tablet)
Immediate release section total alkaloid of corydalis rhizome 2.5 grams
Lactose 50 grams
Starch 50 grams
Magnesium Stearate is an amount of
Slow-released part total alkaloid of corydalis rhizome 5 grams
Hydroxypropyl methyl fiber 75 grams
Plain
Starch 25 grams
Magnesium Stearate is an amount of
Make 1000
By above-mentioned immediate release section and slow-released part recipe quantity sieve respectively, mixing, granulate, dry, whole grain, add starch, Magnesium Stearate mixing; Immediate release section and slow-released part are pressed into double-layer tablets in the prescription ratio.
Embodiment 15: a kind of preparation---the freeze-dried powder of total alkaloid of corydalis rhizome
Total alkaloid of corydalis rhizome 2 grams
N.F,USP MANNITOL is an amount of
Make 1000
Get total alkaloid of corydalis rhizome 2 grams, add 1% hydrochloric acid soln and make dissolving, add an amount of N.F,USP MANNITOL, regulate pH 4~5 with 1% sodium hydroxide solution again, cross the millipore filtration of 0.2 μ m, packing, freeze-drying, promptly.

Claims (11)

1. a method for preparing total alkaloid of corydalis rhizome comprises the following steps:
(1) dry tuber of papaveracease Corydalis plant Rhizome of Decumbent Corydalis is a raw material, the aqueous acid that adds 2~3 times of this crude drug in whole raw material weights soaked after 12~36 hours, continue to carry out the diacolation extraction with the aqueous acid of 5~20 times of crude drug in whole raw material weights, 1~3 day extraction time, collect percolate to the lifeless matter alkali reaction, merge percolate;
(2) step (1) gained percolate is carried out macroporous adsorption resin chromatography, remove impurity towards post successively with the diluted acid and the dilute alkaline aqueous solution of 1~5 times of crude drug in whole raw material weight respectively then;
(3) with the macroporous adsorptive resins of step (2) with the high concentration ethanol wash-out of 5~20 times of crude drug in whole raw material weights and collect, wherein, described high concentration ethanol is that concentration is 〉=50% ethanol;
(4) with step (3) gained elutriant again through alumina column absorption, liquid behind the post is collected in further removal of impurities, concentrate the Rhizoma corydalis decumbentis total alkaloids extract,
Wherein, the weight percent of the total alkaloid of corydalis rhizome of gained consists of:
Protopine: 20~30%
Tetrahydropalmatine: 15~25%
Finish withered spirit: 10~15%
Palmatine hydrochloride: 5~10%
Summer is alkali rather: 10~15%
You are bright for corydalis: 5~10%
Other biological alkali and extract: 5~20%.
2. be a kind of in 0.01~10% phosphoric acid, hydrochloric acid, sulfuric acid, the aqueous acetic acid according to the process of claim 1 wherein that the described aqueous acid of step (1) is selected from concentration.
3. according to the process of claim 1 wherein that the described macroporous adsorbent resin of step (2) is selected from a kind of among AL-1, AL-2, D-101, DA-201, DM-301, ADS-5, ADS-8, ME-1, ME-2, the AB-8.
4. be a kind of in 0.01~10% phosphoric acid, hydrochloric acid, sulfuric acid, the aqueous acetic acid according to the process of claim 1 wherein that the described diluted acid of step (2) is selected from concentration; It is a kind of in 0.01~15% potassium hydroxide, sodium hydroxide, the ammonia aqueous solution that described diluted alkaline is selected from concentration.
5. according to the process of claim 1 wherein that the described aluminum oxide of step (4) is neutral alumina or alkali alumina, its granularity is 100~300 orders.
6. extract the total alkaloid of corydalis rhizome extract that obtains by each method among the claim 1-5, it is characterized in that wherein the weight percent of total alkaloids consists of:
Protopine: 20~30%
Tetrahydropalmatine: 15~25%
Finish withered spirit: 10~15%
Palmatine hydrochloride: 5~10%
Summer is alkali rather: 10~15%
You are bright for corydalis: 5~10%
Other biological alkali and extract: 5~20%.
7. total alkaloid of corydalis rhizome extract according to claim 6 is characterized in that, its total alkaloid content is measured with UV method or HPLC method and is no less than 85%.
8. pharmaceutical composition, it contains described total alkaloid of corydalis rhizome extract of the claim 6 for the treatment of significant quantity and pharmaceutically acceptable carrier.
9. the application of the pharmaceutical composition of claim 8 in useful in preparing drug formulations.
10. application as claimed in claim 9, wherein said pharmaceutical preparation are tablet, capsule, suppository, granule, transdermal absorption formulation, dripping pill, oral rapidly disintegrating formulation, sustained-release preparation or lyophilized injectable powder.
11. application as claimed in claim 10, wherein said capsule is a soft capsule.
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Publication number Priority date Publication date Assignee Title
CN101893607B (en) * 2009-05-22 2013-05-29 上海医药工业研究院 Method for determining decumbent corydalis tuber total alkaloid extractive content with UFLC and method for establishing UFLC finger print thereof
CN103610762B (en) * 2013-12-12 2015-04-29 山东金诃药物研究开发有限公司 Extract of corydalis impatiens total alkaloids and extraction method thereof
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CN105367580B (en) * 2014-08-29 2018-06-12 上海医药工业研究院 A kind of preparation method of decumbent corydalis tuber alkaloid monomer
CN106722839B (en) * 2016-12-05 2020-06-23 桂林莱茵生物科技股份有限公司 Preparation method of momordica grosvenori bittering agent
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CN108519450B (en) * 2017-06-05 2021-03-16 广州市药品检验所 Rhizoma corydalis reference extract and preparation method and application thereof
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CN110559298A (en) * 2019-10-28 2019-12-13 中国药科大学 Application of natural compound Egenine in preparation of anti-renal fibrosis drugs
CN112915583A (en) * 2021-02-01 2021-06-08 金华寿仙谷药业有限公司 Purification system and purification process of lotus leaf alkaloid monomer

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1445227A (en) * 2002-03-20 2003-10-01 苏州中药研究所 Method for extracting total alkaloid of corydalis rhizome and its new usage
CN1456153A (en) * 2003-03-21 2003-11-19 毛友昌 Preparing method for Xiatianwu alkaloids
CN1535969A (en) * 2003-04-11 2004-10-13 湖南医药工业研究所 Total alkaloid of xiatianwu (a Chinese medicinal material), its preparation method and application
CN1683372A (en) * 2005-03-11 2005-10-19 上海医药工业研究院 Method for extracting protopine from decumbent corydalis tuber

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1445227A (en) * 2002-03-20 2003-10-01 苏州中药研究所 Method for extracting total alkaloid of corydalis rhizome and its new usage
CN1456153A (en) * 2003-03-21 2003-11-19 毛友昌 Preparing method for Xiatianwu alkaloids
CN1535969A (en) * 2003-04-11 2004-10-13 湖南医药工业研究所 Total alkaloid of xiatianwu (a Chinese medicinal material), its preparation method and application
CN1683372A (en) * 2005-03-11 2005-10-19 上海医药工业研究院 Method for extracting protopine from decumbent corydalis tuber

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