CN105311119A - Refined rhizoma corydalis decumbentis total alkaloid product, preparation method thereof, pharmaceutical composition and application of refined rhizoma corydalis decumbentis total alkaloid product and pharmaceutical composition - Google Patents
Refined rhizoma corydalis decumbentis total alkaloid product, preparation method thereof, pharmaceutical composition and application of refined rhizoma corydalis decumbentis total alkaloid product and pharmaceutical composition Download PDFInfo
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Abstract
The invention discloses a refined rhizoma corydalis decumbentis total alkaloid product, a preparation method thereof, a pharmaceutical composition and application of the refined rhizoma corydalis decumbentis total alkaloid product and the pharmaceutical composition. The refined rhizoma corydalis decumbentis total alkaloid product comprises, by weight, 15%-40% of protopine, 10%-40% of tetrahydropalmatine, 0-10% of bicuculline, 0.01%-2% of palmatine hydrochloride, 2%-10% of kikemanine, 15%-30% of egenine and 1%-5% of other alkaloids and extracts. The more scientific and efficient, simple, convenient and feasible method for extracting high-purity rhizoma corydalis decumbentis total alkaloids is established, and HPLC (high performance liquid chromatography) purity of the prepared refined rhizoma corydalis decumbentis total alkaloid product is above 98%, so that pharmacology and efficacy of the rhizoma corydalis decumbentis total alkaloids can be given to play more safely and effectively.
Description
Technical field
The present invention relates to total alkaloid of corydalis rhizome and refine thing, preparation method, pharmaceutical composition and application.
Background technology
Rhizoma Corydalis Decumbentis is dry tuber or the herb of Papaveraceae Genus Corydalis Hotseason grow Corydalisdecumbens (Thunb.) Pers., is that China commonly uses Chinese herbal medicine, the effects such as tool is invigorated blood circulation, dredging collateral, circulation of qi promoting, pain relieving.Cure mainly hypertension, apoplectic hemiplegia that cerebrovascular causes, and have good effect to rheumatic arthritis, sciatica, poliomyelitis sequela etc.Its principle active component is iloquinoline derivative total alkaloids.Documents and materials display has been separated and has obtained more than 30 isoquinoline alkaloid from Rhizoma Corydalis Decumbentis, mainly containing alkaloids such as protopine (protopine), tetrahydropalmatine (tetrahydropalmatine), Bicuculline (bicuculline), palmatine (palmatine), jateorhizine.
At present, the extracting and purifying method that Rhizoma corydalis decumbentis total alkaloids is conventional has water extract-alcohol precipitation, percolation, alcohol extraction, acid-base method.Along with the application of Modern preparations technology, macroporous adsorbent resin, ultrasonic, Ultra filtration membrane, supercritical CO
2the methods such as extraction are also applied to the purifying of Rhizoma corydalis decumbentis total alkaloids gradually.Horse HTC etc. have studied supercritical CO
2extraction extracts the process conditions of total alkaloids in Rhizoma Corydalis Decumbentis.With extracting pressure, extraction temperature and extraction time for investigating factor, with the comprehensive grading of total alkaloid of corydalis rhizome, protopine, Content determination of dl-tetrahydropalmatine and dry cream rate for evaluation index, adopt the preferred optimum process condition of orthogonal test.Result: optimum process condition is extracting pressure 30MPa, extraction temperature 55 DEG C, extraction time 2.5h.In extract, total alkaloid content is about 67%, and protopine content is about 17%, and Content determination of dl-tetrahydropalmatine is about 10%.(horse HTC, An Ye, Guo Tao etc.Supercritical CO
2extraction extracts total alkaloid of corydalis rhizome technical study [J]. China Dispensary, 2010,21 (47): 4456-4458) Zhu Caiqing etc. adopt and retain Rhizoma corydalis decumbenti Injection clarification that relative molecular mass is the optimal experimental design of 6 × 103 ~ 1.0 × 104, color and luster is good, demonstrates stronger drug action.Zhu Caiqing, Yu Hua, Fan Qikun, etc. the research of ultrafilter membrane purification Rhizoma corydalis decumbentis total alkaloids. Chinese herbal medicine, 2005,36 (9): 1319-1325.
A kind of Rhizoma corydalis decumbentis extract of CN101058576 disclosure of the invention and preparation method thereof, its preparation method is with raw material of doing nothing summer, utilize supercritical CO
2fluid extraction condition is extracted, and collects extract, dry Rhizoma corydalis decumbentis total alkaloids extract.The total alkaloid of corydalis rhizome average content that application this law is extracted adopts UV method to be determined as 90%, wherein total alkaloids mainly comprises protopine, tetrahydropalmatine, Bicuculline, palmatine hydrochloride, bright, summer rather alkali and the related alkaloids of Herba corydalis edulis that, and the content of six main alkali accounts for 75% ~ 90% of extract.
A kind of preparation method of total alkaloid of corydalis rhizome hydrochlorate lyophilized products is the invention discloses, with Rhizoma Corydalis Decumbentis supercritical CO in CN101623332
2total alkaloids extract is raw material, adds aqueous acid and makes it dissolve, obtain the aqueous acid of total alkaloid of corydalis rhizome; Filter or centrifugal rear filtration, by settled solution lyophilization, obtain total alkaloid of corydalis rhizome hydrochlorate lyophilized products.
Above-mentioned two patents all provide a kind of method preparing total alkaloid of corydalis rhizome, but have weak point.CN101058576 provide only the total biological method of Rhizoma Corydalis Decumbentis supercritical extraction Rhizoma Corydalis Decumbentis, prepares extract obtainedly to be difficult to drying containing oils composition, to hinder the Application and Development that it is follow-up, and to extraction time and CO
2flow velocity limits, and is difficult to be applied to suitability for industrialized production.
CN101623332B patent on CN101058576B basis with the total alkaloid of corydalis rhizome crude extract of Rhizoma Corydalis Decumbentis supercritical extraction for the method for total alkaloids hydrochlorate lyophilized products to be prepared by raw material by acid solution process postlyophilization, prepare the content of the lyophilized products total alkaloids of gained more than 80%.This patent is not done further study the enrichment of total alkaloid of corydalis rhizome, purification, and obtained Rhizoma Corydalis Decumbentis extract purity is not high enough, limits the range of application of total alkaloid of corydalis rhizome.
Clinical being mainly used in of total alkaloid of corydalis rhizome preparation treats senile dementia, cerebral infarction, students in middle and primary schools' pseudomyopia etc., there is very large market prospect, but resin column method was put forward in extraction and separation technology many employings acid of current total alkaloid of corydalis rhizome, cumbersome, length consuming time, the shortcoming that the purity of the total alkaloids obtained is not high.Therefore, the purity extracting method that is good, that be suitable for large-scale industrial production finding the total alkaloid of corydalis rhizome that technique is simple, extraction ratio is high, extract is the technical barrier being badly in need of at present solving.
Summary of the invention
The technical problem to be solved in the present invention is that existing total alkaloid of corydalis rhizome extracting method complex steps, extraction ratio are low, to extract the extract purity obtained low in order to overcome, impurity content is high, be not suitable for medicinal, be not suitable for the defects such as suitability for industrialized production, and provide a kind of total alkaloid of corydalis rhizome and refine thing, preparation method, pharmaceutical composition and application.The present invention establishes more scientific efficient highly purified total alkaloid of corydalis rhizome extracting method, and the method is efficient, simple and easy to do, and the HPLC purity of the total alkaloid of corydalis rhizome of preparation is greater than 98%, the pharmacological effect of performance total alkaloid of corydalis rhizome that can be safer and more effective.
The invention provides a kind of total alkaloid of corydalis rhizome and refine thing, wherein, the percentage by weight that total alkaloids refines each component in thing is respectively: protopine: 15% ~ 40%; Tetrahydropalmatine: 10% ~ 40%; Bicuculline: 0 ~ 10% (not comprising 0); Palmatine hydrochloride: 0.01% ~ 2%; You are bright for Herba corydalis edulis: 2% ~ 10%; Summer is alkali rather: 15% ~ 30%; Related alkaloids and extract: 1% ~ 5%.
In the present invention, described total alkaloid of corydalis rhizome refines thing, and adopt HPLC method to measure, total alkaloid content is 60% ~ 100%, wherein, six main total alkali contents account for that total alkaloid of corydalis rhizome refines thing more than 95%.
Present invention also offers the preparation method that described total alkaloid of corydalis rhizome refines thing, it comprises the following steps:
Step 1: with the tuber of Rhizoma Corydalis Decumbentis (bloodroot Hotseason grow), pulverizing, alkalization, obtains the Rhizoma Corydalis Decumbentis after alkalizing; In described alkalization, the mass values of described alkali and described Rhizoma Corydalis Decumbentis is 0.001 ~ 1, preferably 0.001 ~ 0.1.
Step 2: the Rhizoma Corydalis Decumbentis after alkalization step 1 obtained, at supercritical CO
2extraction and fractionation is carried out in the abstraction instrument that extraction and membrance separation are coupled, dry, obtain total alkaloid of corydalis rhizome and refine thing.
In step 1, described pulverizing, the particle diameter that preferred powder is broken to Rhizoma Corydalis Decumbentis (bloodroot Hotseason grow) is 10 order ~ 60 orders (i.e. 1.74mm ~ 0.273mm).Described alkalization, preferred employing inorganic base alkalizes, one or more in the preferred ammonia spirit of described inorganic base, calcium hydroxide, sodium carbonate and sodium bicarbonate, preferred ammonia spirit further, the mass concentration of described ammonia spirit preferably 1% ~ 10%, described mass concentration refers to that the quality of ammonia accounts for the percentage ratio of ammonia spirit gross mass.Described ammonia spirit can adopt ammonia reagent and water to be mixed to get, and described ammonia reagent and the volume ratio of water preferably 5% ~ 10%, described volume ratio refers to the volume of ammonia reagent and the percentage ratio of water volume.Described ammonia reagent can be conventional commercial ammonia reagent in this area, the concentration of described ammonia reagent preferably 2% ~ 30%.Described inorganic base preferably uses with the form of its aqueous solution, and the concentration of the aqueous solution of described inorganic base preferably 1% ~ 10%, described concentration refers to that the quality of inorganic base accounts for the percentage ratio of the gross mass of the aqueous solution of inorganic base.
In step 2, described supercritical CO
2the time preferably 0.5 ~ 5h of extraction and fractionation; Described supercritical CO
2the entrainer particular methanol adopted during extraction and fractionation and/or ethanol, further preferred alcohol, described ethanol preferred mass percentage ratio is the ethanol water of 95%, and described mass percent refers to that the quality of ethanol accounts for the percentage ratio of ethanol water gross mass.Described " supercritical CO
2extraction and the abstraction instrument that is coupled of membrance separation " in the preferred ultrafilter membrane of film, NF membrane, reverse osmosis membrane or hollow-fibre membrane, preferred NF membrane further; Aperture preferably 1 nanometer ~ 3 nanometer of described NF membrane.Preferred nanometer 10 nanometer ~ 40, the aperture nanometer of described ultrafilter membrane.Aperture preferably 1 nanometer ~ 5 nanometer of described reverse osmosis membrane.Aperture preferably 1 nanometer ~ 40 nanometer of described hollow-fibre membrane.
In step 2, described supercritical CO
2the abstraction instrument that extraction and membrance separation are coupled is assembled according to the schematic diagram recorded in " Chinese medicine extraction separation technology " book (in April, 2010, Chemical Industry Press publishes, P353 page), described supercritical CO
2the abstraction instrument that extraction and membrance separation are coupled comprises with lower component: extraction equipment, segregation apparatus, high-pressure pump, film device, cooler and gas reservoir.
In the present invention, the preparation method that described total alkaloid of corydalis rhizome refines thing preferably also comprises step 3, preferably also comprises step 3 and step 4 further, more preferably also comprises step 3, step 4 and step 5 further.
Step 3: total alkaloid of corydalis rhizome step 2 obtained is refined thing and regulated pH to 2 ~ 5, adopts ultrasonic extraction, then adopts ultrafiltration or micro-filtrate membrane filtration, obtains the solution that the total alkaloid of corydalis rhizome after purification refines thing.
Step 4: the solution that total alkaloid of corydalis rhizome step 3 obtained refines thing regulates pH to be 8 ~ 12, and filter, solid phase washes with water to neutrality, obtains the total alkaloid of corydalis rhizome after being further purified and refines thing;
Step 5: step 4 is obtained be further purified after total alkaloid of corydalis rhizome refine thing recrystallization, obtain the total alkaloid of corydalis rhizome after recrystallization and refine thing.
In step 3, the preferred 30Hz ~ 80Hz of frequency of described ultrasonic extraction, preferably 0.5 hour ~ 3 hours time of described ultrasonic extraction.Preferably 0.3 micron ~ 0.8 micron, described ultrafiltration or the aperture of micro-filtration membrane; Described adjustment pH preferably regulates with acid, the preferred mineral acid of described acid and/or organic acid, the preferred hydrochloric acid of described mineral acid, the preferred tartaric acid of described organic acid.Described acid preferably uses with the form of its aqueous solution, when described acid uses with the form of its aqueous solution, the mass percentage concentration of described aqueous acid preferably 1% ~ 10%, further preferably 1% ~ 5%, described mass percent refers to that the quality of acid accounts for the percentage ratio of aqueous acid gross mass.The volume ratio of the refining thing of the total alkaloid of corydalis rhizome that described aqueous acid and described step 2 obtain preferably 5 ~ 10, further preferably 5 ~ 8.Step 3 preferably includes dry step, and the solution drying of the total alkaloid of corydalis rhizome after described purification being refined thing obtains the total alkaloid of corydalis rhizome after purification and refines thing; Described drying can according to the conventional method of this generic operation in this area and condition.
In step 4, described pH is preferably 9 ~ 11.Described adjustment pH preferably adopts inorganic base to regulate, the preferred sodium hydroxide of described inorganic base or potassium hydroxide, described inorganic base can use with the form of its aqueous solution, when described inorganic base uses with the form of its aqueous solution, the mass concentration of the aqueous solution of described inorganic base preferably 3% ~ 15%, further preferably 4% ~ 10%, described mass concentration refers to that the quality of inorganic base accounts for the percentage ratio of inorganic base aqueous solution gross mass.Step 4 preferably includes dry step, and described drying can according to the conventional method of this generic operation in this area and condition.
In step 5, described recrystallization can adopt conventional method and the condition of this generic operation in this area.The solvent preferred alcohols kind solvent that described recrystallization adopts and/or halogenated hydrocarbon solvent, described alcohols solvent particular methanol and/or ethanol, the preferred chlorinated hydrocarbon solvent of described halogenated hydrocarbon solvent, the preferred chloroform of described chlorinated hydrocarbon solvent.Step 5 preferably includes dry step, and described drying can according to the conventional method of this generic operation in this area and condition.
The refining thing that present invention also offers described total alkaloid of corydalis rhizome treats and/or prevents the application in the medicine of the disease of the neuronal cell injury that cerebral ischemia or Reperfu-sion cause in preparation.
Present invention also offers a kind of pharmaceutical composition, it contains the refining thing of the described total alkaloid of corydalis rhizome for the treatment of effective dose and pharmaceutically acceptable carrier.In the present invention, described treatment effective dose preferred mass percentage ratio is 0.1% ~ 99.9%, and described mass percent refers to that the refining thing of described total alkaloid of corydalis rhizome accounts for the percentage ratio of pharmaceutical composition gross mass.Described pharmaceutically acceptable carrier is pharmaceutically acceptable carrier conventional in this area.
Present invention also offers described pharmaceutical composition and treat and/or prevent application in the medicine of the disease of the neuronal cell injury that cerebral ischemia or Reperfu-sion cause in preparation.
In the present invention, the disease of the neuronal cell injury that described cerebral ischemia or Reperfu-sion cause comprises cerebral thrombosis and apoplexy.
Without prejudice to the field on the basis of common sense, above-mentioned each optimum condition, can combination in any, obtains the preferred embodiments of the invention.
Agents useful for same of the present invention and raw material are all commercially.
Positive progressive effect of the present invention is: the present invention establishes the extracting method of more scientific efficient highly purified total alkaloid of corydalis rhizome, the method is efficient, simple and easy to do, the HPLC purity that the total alkaloid of corydalis rhizome prepared refines thing is greater than 98%, the pharmacological effect of performance total alkaloid of corydalis rhizome that can be safer and more effective.
Accompanying drawing explanation
Fig. 1 is CO
2the schematic diagram of the extraction process that supercritical extraction and membrance separation are coupled.
Detailed description of the invention
Mode below by embodiment further illustrates the present invention, but does not therefore limit the present invention among described scope of embodiments.The experimental technique of unreceipted actual conditions in the following example, conventionally and condition, or selects according to catalogue.
The supercritical CO adopted in the following example
2the abstraction instrument of extraction and film coupling assembles according to the schematic diagram shown in Fig. 1.
Embodiment 1: total alkaloid of corydalis rhizome refines the preparation of thing
Get the dry tuber of Rhizoma Corydalis Decumbentis, pulverize, obtaining granularity is 10 order ~ 40 object medicinal powders; Get medicinal powder 300g, adding volume ratio is that as basifier, (described volume ratio refers to that the volume of ammonia reagent accounts for the percentage ratio of ammonia spirit cumulative volume to 6% ammonia, the mass concentration of ammonia reagent is 25% ~ 28%, described mass concentration refers to that the quality of ammonia accounts for the percentage ratio of ammonia reagent gross mass), consumption is 50% of decumbent corydalis as medicine material weight, infiltrates 2h; Medical material is dropped into supercritical CO
2in the abstraction instrument of extraction and film coupling (aperture is the ultrafilter membrane of 0.8 micron), take methanol as entrainer, extract after 30 minutes, stop extraction, obtain total alkaloids extract, dry, to obtain final product.High effective liquid chromatography for measuring total alkaloid content is 98.47%.Measure through HPLC, its percentage by weight composition comprises: protopine: 34.89%, tetrahydropalmatine: 24.56%, Bicuculline: 3.51%, palmatine hydrochloride: 1.84%, the summer is alkali rather: 19.77%, you are bright for Herba corydalis edulis: 9.58%, other alkali contents 4.32%.
Embodiment 2: total alkaloid of corydalis rhizome refines the preparation of thing
Get the dry tuber of Rhizoma Corydalis Decumbentis, pulverize, obtaining granularity is 20 order ~ 40 object medicinal powders; Get medicinal powder 300g, adding volume ratio is that as basifier, (described volume ratio refers to that the volume of ammonia reagent accounts for the percentage ratio of ammonia spirit cumulative volume to 10% ammonia, the mass concentration of ammonia reagent is 25% ~ 28%, described mass concentration refers to that the quality of ammonia accounts for the percentage ratio of ammonia reagent gross mass), consumption is 60% of decumbent corydalis as medicine material weight, infiltrates 1h; Medical material is dropped into supercritical CO
2in the abstraction instrument of extraction and film coupling (employing aperture is the NF membrane of 2 nanometers), be that 95% ethanol is for entrainer (described mass percent refers to that the quality of ethanol accounts for the percentage ratio of ethanol water gross mass) with mass percent, extraction time 1.5h, high effective liquid chromatography for measuring total alkaloid content is 98.95%.Measure through HPLC, its percentage by weight composition comprises: protopine: 30.52%, tetrahydropalmatine: 28.93%, Bicuculline: 0.01%, palmatine hydrochloride: 0.09%, the summer is alkali rather: 25.64%, you are bright for Herba corydalis edulis: 9.73%, other alkali contents 4.03%.
Embodiment 3: total alkaloid of corydalis rhizome refines the preparation method of thing
Get the dry tuber of Rhizoma Corydalis Decumbentis, beat powder, obtaining granularity is 10 order ~ 20 object medicinal powders; Get medicinal powder 200g, adding volume ratio is that as basifier, (described volume ratio refers to that the volume of ammonia reagent accounts for the percentage ratio of ammonia spirit cumulative volume to 7% ammonia spirit, the mass concentration of ammonia reagent is 25% ~ 28%, described mass concentration refers to that the quality of ammonia accounts for the percentage ratio of ammonia reagent gross mass), consumption is 50% of decumbent corydalis as medicine material weight, infiltrates 3h; Medical material is dropped into supercritical CO
2in the abstraction instrument of extraction and film coupling (employing aperture is the hollow-fibre membrane of 0.1 micron), be that 95% ethanol is for entrainer (described mass percent refers to that the quality of ethanol accounts for the percentage ratio of ethanol water gross mass) with mass percent, extraction time 40 minutes, the total alkaloids mass percent obtained is 1% aqueous hydrochloric acid solution 300mL (described mass percent refers to that the quality of hydrogen chloride accounts for the percentage ratio of aqueous hydrochloric acid solution gross mass), and ultrasonic (supersonic frequency is 80H
z) extraction 2h, 1.0 μm of filter membranes filter, adding mass percent is that 8% potassium hydroxide solution adjusts pH10 ~ 11 (described mass percent refers to that the quality of potassium hydroxide accounts for the percentage ratio of potassium hydroxide gross mass), filter to obtain precipitation, high effective liquid chromatography for measuring total alkaloid content is 98.88%.Measure through HPLC, its percentage by weight composition comprises: protopine: 35.68%, tetrahydropalmatine: 19.36%, Bicuculline: 4.64%, palmatine hydrochloride: 0.61%, the summer is alkali rather: 28.71%, you are bright for Herba corydalis edulis: 8.75%, other alkali contents 1.13%.
Embodiment 4: total alkaloid of corydalis rhizome refines the preparation method of thing
Get the dry tuber of Rhizoma Corydalis Decumbentis, beat powder, obtaining granularity is 20 order ~ 40 object decumbent corydalis as medicine material powder; Get decumbent corydalis as medicine material powder 300g, (described volume ratio refers to that the volume of ammonia reagent accounts for the percentage ratio of ammonia spirit cumulative volume as basifier to add volume ratio 10% ammonia, the mass concentration of ammonia reagent is 25% ~ 28%, described mass concentration refers to that the quality of ammonia accounts for the percentage ratio of ammonia reagent gross mass), consumption is 50% of decumbent corydalis as medicine material weight, infiltrates 2.5h; Medical material is dropped into supercritical CO
2in the abstraction instrument of extraction and film coupling (employing aperture is the composite nanometer filtering film of 1 nanometer), be that 95% ethanol is for entrainer (described mass percent refers to that the quality of ethanol accounts for the percentage ratio of ethanol water gross mass) with mass percent, extract after 1 hour, to obtain final product.Be 1% aqueous hydrochloric acid solution 500ml, ultrasonic (supersonic frequency 60H by mass percent
z) extraction 1h, 0.45 μm of filter membrane filters, adding mass percent is that 10% sodium hydroxide solution adjusts pH9 ~ 10 (described mass percent refers to that the quality of potassium hydroxide accounts for the percentage ratio of potassium hydroxide gross mass), filter to obtain precipitation, high effective liquid chromatography for measuring total alkaloid content is 98.68%.Measure through HPLC, its percentage by weight composition comprises: protopine: 20.68%, tetrahydropalmatine: 32.16%, Bicuculline: 8.84%, palmatine hydrochloride: 0.50%, and the summer is alkali rather: 28.71%, and you are bright for Herba corydalis edulis: 6.75%, other alkali 1.04%.
Embodiment 5: total alkaloid of corydalis rhizome refines the preparation method of thing
Get the dry tuber of Rhizoma Corydalis Decumbentis, beat powder, obtaining granularity is 30 order ~ 40 object decumbent corydalis as medicine material powder; Get decumbent corydalis as medicine material powder 8000g, adding volume ratio is that as basifier, (described volume ratio refers to that the volume of ammonia reagent accounts for the percentage ratio of ammonia spirit cumulative volume to 10% ammonia, the mass concentration of ammonia reagent is 25% ~ 28%, described mass concentration refers to that the quality of ammonia accounts for the percentage ratio of ammonia reagent gross mass), consumption is 70% of decumbent corydalis as medicine material weight, infiltrates 24h; Medical material is dropped into supercritical CO
2in the abstraction instrument of extraction and film coupling (adopting aperture to be 15 nanometer reverse osmosis membranes), be that 95% ethanol is for entrainer (described mass percent refers to that the quality of ethanol accounts for the percentage ratio of ethanol water gross mass) with mass percent, extraction time 1h, dry, to obtain final product.Be 2% aqueous hydrochloric acid solution 300mL (described mass percent refers to that the quality of hydrogen chloride accounts for the percentage ratio of aqueous hydrochloric acid solution gross mass) by mass percent again, ultrasonic (supersonic frequency 80H
z) extraction 0.5h, aperture is that the filter membrane of 0.1 micron filters, adding mass percent is that 10% sodium hydroxide solution adjusts pH9 ~ 10 (described mass percent refers to that the quality of sodium hydroxide accounts for the percentage ratio of sodium hydroxide gross mass), filter to obtain precipitation, by recrystallizing methanol, high effective liquid chromatography for measuring total alkaloid content is 99.88%.Measure through HPLC, its percentage by weight composition comprises: protopine: 29.28%, tetrahydropalmatine: 23.83%, Bicuculline: 8.52%, palmatine hydrochloride: 1.90%, and the summer is alkali rather: 29.71%, and you are bright for Herba corydalis edulis: 4.62%, other alkali 2.02%.
Claims (17)
1. total alkaloid of corydalis rhizome refines a thing, it is characterized in that: the percentage by weight that total alkaloids refines each component in thing is respectively: protopine: 15% ~ 40%; Tetrahydropalmatine: 10% ~ 40%; Bicuculline: 0 ~ 10% (not comprising 0); Palmatine hydrochloride: 0.01% ~ 2%; You are bright for Herba corydalis edulis: 2% ~ 10%; Summer is alkali rather: 15% ~ 30%; Related alkaloids and extract: 1% ~ 5%.
2. total alkaloid of corydalis rhizome as claimed in claim 1 refines the preparation method of thing, it is characterized in that: step 1: with the tuber of Rhizoma Corydalis Decumbentis, pulverizing, alkalization, and obtain the Rhizoma Corydalis Decumbentis after alkalizing, the mass values of described alkali and described Rhizoma Corydalis Decumbentis is 0.001 ~ 1;
Step 2: the Rhizoma Corydalis Decumbentis after alkalization step 1 obtained, at supercritical CO
2extraction and fractionation is carried out in the abstraction instrument that extraction and membrance separation are coupled, dry, obtain described total alkaloid of corydalis rhizome and refine thing.
3. total alkaloid of corydalis rhizome as claimed in claim 2 refines the preparation method of thing, it is characterized in that: in step 1, described pulverizing, for the particle diameter being crushed to Rhizoma Corydalis Decumbentis is 10 order ~ 60 orders;
And/or,
In step 1, described alkalization, adopts inorganic base to alkalize;
And/or,
In alkalization described in step 1, the mass values of described alkali and described Rhizoma Corydalis Decumbentis is 0.001 ~ 0.1.
4. total alkaloid of corydalis rhizome as claimed in claim 3 refines the preparation method of thing, it is characterized in that: in step 1, and described inorganic base is one or more in ammonia spirit, calcium hydroxide, sodium carbonate and sodium bicarbonate; When adopting ammonia spirit to alkalize, the mass concentration of described ammonia spirit is 1% ~ 10%, and described mass concentration refers to that the quality of ammonia accounts for the percentage ratio of ammonia spirit gross mass.
5. total alkaloid of corydalis rhizome as claimed in claim 2 refines the preparation method of thing, and it is characterized in that: in step 2, the time of described extraction and fractionation is 0.5 ~ 5h;
And/or,
In step 2, the entrainer adopted during described extraction and fractionation is methanol and/or ethanol;
And/or,
In step 2, described " supercritical CO
2extraction and the abstraction instrument that is coupled of membrance separation " in film be ultrafilter membrane, NF membrane, reverse osmosis membrane or hollow-fibre membrane.
6. total alkaloid of corydalis rhizome as claimed in claim 2 refines the preparation method of thing, it is characterized in that: the preparation method that described total alkaloid of corydalis rhizome refines thing also comprises step 3, step 3: total alkaloid of corydalis rhizome step 2 obtained is refined thing and regulated pH to 2 ~ 5, adopt ultrasonic extraction, then adopt ultrafiltration or micro-filtrate membrane filtration, obtain the solution that the total alkaloid of corydalis rhizome after purification refines thing.
7. total alkaloid of corydalis rhizome as claimed in claim 6 refines the preparation method of thing, and it is characterized in that: in step 3, the frequency of described ultrasonic extraction is 30Hz ~ 80Hz;
And/or,
In step 3, the time of described ultrasonic extraction is 0.5 hour ~ 3 hours;
And/or,
In step 3, described ultrafiltration or the aperture of micro-filtration membrane are 0.3 micron ~ 0.8 micron;
And/or,
In step 3, described adjustment pH acid regulates, and described acid is mineral acid and/or organic acid.
8. total alkaloid of corydalis rhizome as claimed in claim 7 refines the preparation method of thing, and it is characterized in that: in step 3, described mineral acid is hydrochloric acid;
And/or,
In step 3, described organic acid is tartaric acid;
And/or,
In step 3, described acid uses with the form of its aqueous solution, and when described acid uses with the form of its aqueous solution, the mass percentage concentration of described aqueous acid is 1% ~ 10%; Described mass percent refers to that the quality of acid accounts for the percentage ratio of aqueous acid gross mass; The volume ratio that the total alkaloid of corydalis rhizome that described aqueous acid and described step 2 obtain refines thing is 5 ~ 10;
And/or,
Step 3 comprises dry step, and the solution drying of the total alkaloid of corydalis rhizome after described purification being refined thing obtains the total alkaloid of corydalis rhizome after purification and refines thing.
9. total alkaloid of corydalis rhizome as claimed in claim 6 refines the preparation method of thing, it is characterized in that: the preparation method that described total alkaloid of corydalis rhizome refines thing also comprises step 4, step 4: the solution that total alkaloid of corydalis rhizome step 3 obtained refines thing regulates pH to be 8 ~ 12, filter, solid phase washes with water to neutrality, obtains the total alkaloid of corydalis rhizome after being further purified and refines thing.
10. total alkaloid of corydalis rhizome as claimed in claim 9 refines the preparation method of thing, and it is characterized in that: in step 4, described pH is 9 ~ 11; And/or in step 4, described adjustment pH adopts inorganic base to regulate.
11. total alkaloid of corydalis rhizome as claimed in claim 10 refine the preparation method of thing, and it is characterized in that: in step 4, described inorganic base is sodium hydroxide or potassium hydroxide;
And/or,
In step 4, described inorganic base uses with the form of its aqueous solution, and when described inorganic base uses with the form of its aqueous solution, the mass concentration of the aqueous solution of described inorganic base is 3% ~ 15%; Described mass concentration refers to that the quality of inorganic base accounts for the percentage ratio of inorganic base aqueous solution gross mass;
And/or,
Step 4 comprises dry step.
12. total alkaloid of corydalis rhizome as claimed in claim 9 refine the preparation method of thing, it is characterized in that: the preparation method that described total alkaloid of corydalis rhizome refines thing also comprises step 5, step 5: step 4 is obtained be further purified after total alkaloid of corydalis rhizome refine thing recrystallization, obtain the total alkaloid of corydalis rhizome after recrystallization and refine thing.
13. total alkaloid of corydalis rhizome as claimed in claim 12 refine the preparation method of thing, it is characterized in that: in step 5, and the solvent that described recrystallization adopts is alcohols solvent and/or halogenated hydrocarbon solvent.
14. total alkaloid of corydalis rhizome as claimed in claim 13 refine the preparation method of thing, and it is characterized in that: in step 5, described alcohols solvent is methanol and/or ethanol;
And/or,
In step 5, described halogenated hydrocarbon solvent is chlorinated hydrocarbon solvent, preferred chloroform.
15. 1 kinds of pharmaceutical compositions, is characterized in that: the total alkaloid of corydalis rhizome as claimed in claim 1 containing treatment effective dose refines thing and pharmaceutically acceptable carrier; Described treatment effective dose preferred mass percentage ratio is 0.1% ~ 99.9%, and described mass percent refers to that the refining thing of described total alkaloid of corydalis rhizome accounts for the percentage ratio of pharmaceutical composition gross mass.
16. total alkaloid of corydalis rhizome as claimed in claim 1 refine thing or pharmaceutical composition as claimed in claim 15, treat and/or prevent the application in the medicine of the disease of the neuronal cell injury that cerebral ischemia or Reperfu-sion cause in preparation.
17. apply as claimed in claim 16, it is characterized in that: the disease of the neuronal cell injury that described cerebral ischemia or Reperfu-sion cause comprises cerebral thrombosis and apoplexy.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107176960A (en) * | 2016-03-10 | 2017-09-19 | 江苏康缘药业股份有限公司 | A kind of alkaloid compound and its preparation and application |
| CN110141605A (en) * | 2019-04-19 | 2019-08-20 | 南京康齐生物科技有限公司 | A kind of preparation method of snowpoppy total alkaloid nanoparticle |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101058576A (en) * | 2006-04-21 | 2007-10-24 | 上海医药工业研究院 | Rhizoma corydalis decumbentis extract, preparation method thereof, medicament composition containing the rhizoma corydalis decumbentis and application thereof |
| CN101623332A (en) * | 2008-07-10 | 2010-01-13 | 上海医药工业研究院 | Method for preparing rhizoma corydalis decumbeutis total alkaloids acid salt freeze-drying substance and application of obtained freeze-drying substance |
-
2014
- 2014-08-04 CN CN201410380316.8A patent/CN105311119A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101058576A (en) * | 2006-04-21 | 2007-10-24 | 上海医药工业研究院 | Rhizoma corydalis decumbentis extract, preparation method thereof, medicament composition containing the rhizoma corydalis decumbentis and application thereof |
| CN101623332A (en) * | 2008-07-10 | 2010-01-13 | 上海医药工业研究院 | Method for preparing rhizoma corydalis decumbeutis total alkaloids acid salt freeze-drying substance and application of obtained freeze-drying substance |
Non-Patent Citations (2)
| Title |
|---|
| 胡雪勇等: "夏天无总碱抗实验性脑缺血的作用", 《中西医结合学报》 * |
| 郭清泉等: "超临界流体耦合技术的现状及发展", 《现代化工》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107176960A (en) * | 2016-03-10 | 2017-09-19 | 江苏康缘药业股份有限公司 | A kind of alkaloid compound and its preparation and application |
| CN107176960B (en) * | 2016-03-10 | 2019-07-12 | 江苏康缘药业股份有限公司 | A kind of alkaloid compound and its preparation and application |
| CN110141605A (en) * | 2019-04-19 | 2019-08-20 | 南京康齐生物科技有限公司 | A kind of preparation method of snowpoppy total alkaloid nanoparticle |
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