CN117466951A - Nepal corydalis total alkaloids and preparation method and application thereof - Google Patents
Nepal corydalis total alkaloids and preparation method and application thereof Download PDFInfo
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- CN117466951A CN117466951A CN202311495680.4A CN202311495680A CN117466951A CN 117466951 A CN117466951 A CN 117466951A CN 202311495680 A CN202311495680 A CN 202311495680A CN 117466951 A CN117466951 A CN 117466951A
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07G—COMPOUNDS OF UNKNOWN CONSTITUTION
- C07G5/00—Alkaloids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/66—Papaveraceae (Poppy family), e.g. bloodroot
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses a corydalis nepalensis total alkaloid and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. Pulverizing and extracting the corydalis nepalensis medicinal material, concentrating the extracting solution to obtain an extract, dissolving the obtained extract with acid liquor, filtering, enriching and purifying to obtain a purified product of the corydalis nepalensis total alkaloids. The total alkaloid content of the corydalis nepalensis prepared by the preparation method can reach 49%, has a good treatment effect on ulcerative colitis of mice induced by Dextran Sodium Sulfate (DSS), and can remarkably relieve the weight reduction of ulcerative colitis mice induced by DSS, reduce DAI score, prolong colon length and reduce inflammatory infiltration degree of colon tissues; regulating biochemical indexes such as inflammation, oxidative stress and the like in colon tissues; has certain regulating effect on intestinal flora.
Description
Technical Field
The invention relates to the technical field of traditional Chinese medicines, in particular to a total alkaloid of corydalis nepalensis, and a preparation method and application thereof.
Background
Ulcerative colitis (ulcerative colitis, UC) is a common inflammatory bowel disease and is manifested clinically by symptoms such as diarrhea, abdominal pain, hematochezia, weight loss, vomiting, etc. In recent years, the incidence rate of UC in emerging industrialized countries rises year by year, and the cure difficulty is high because of the complex etiology and repeated attack of symptoms and long lasting period. At present, the most common treatment methods for UC mainly comprise drug treatment, including glucocorticoid, aminosalicylic acid, immunosuppressant, biological preparation and the like, but a plurality of drugs are limited in clinical application, the clinical curative effect is unstable, even a series of problems such as hepatotoxicity, drug dependence, repeated attack of illness after drug withdrawal and the like can be brought, and some biological preparations are expensive and difficult for common patients to bear, so that searching for new UC treatment drugs with definite curative effect, few side effects and proper price becomes an urgent clinical requirement.
The dried whole herb of corydalis amabilis Corydalis hendersonii hemsl (c.hendersonii) is a perennial herb of the genus corydalis of the family poppy, called nepril, and is mainly distributed in the western part of Xinjiang, the western part of Qinghai and the middle to western part of Tibet in China, and is a traditional Tibetan medicine with long history of application. Aromatic smell, cool and bitter taste, and has effects of clearing heat, relieving inflammation, cooling blood, relieving diarrhea, etc.; has effects of relieving fever, relieving pain, resisting inflammation and resisting oxidation, and can be used for treating altitude erythrocytosis. Modern researches have shown that the Nepal corydalis mainly contains berberine, oripavine, spinosa corydaline, protopine and other alkaloid components. At present, the preparation method and related application of the corydalis amabilis alkaloid are more, but in the field of traditional Chinese medicine chemistry, the components and the pharmacological actions of the obtained preparation are different from each other in different preparation methods and steps.
Disclosure of Invention
The invention aims to provide a total alkaloid of corydalis nepalensis and a preparation method and application thereof, so as to solve the problems in the prior art.
In order to achieve the above object, the present invention provides the following solutions:
the invention provides a preparation method of a total alkaloid of corydalis nepalensis, which comprises the steps of crushing and extracting a medicinal material of the corydalis nepalensis, concentrating an extracting solution to obtain an extract, and dissolving, filtering, enriching and purifying the obtained extract by using acid liquor to obtain a purified product of the total alkaloid of the corydalis nepalensis.
Preferably, the method comprises the following steps:
(1) Pulverizing and sieving herba corydalis Bungeanae medicinal materials to obtain powder, ultrasonic extracting for 2-4 times, filtering, mixing filtrates, and concentrating under reduced pressure to obtain crude extract of herba corydalis Bungeanae;
(2) Dissolving the crude extract of corydalis nepalensis with hydrochloric acid, and filtering to obtain an acidic solution;
(3) Dynamically adsorbing the acidic solution by using macroporous resin XDA-8;
(4) Removing impurities from the macroporous resin after the adsorption is finished, eluting, and recovering the solvent to obtain the final total alkaloids of the corydalis nepalensis.
Preferably, the solvent for ultrasonic extraction is acidic ethanol with ph=1-2.
Preferably, the volume concentration of the ethanol is 70-90%.
Preferably, the mass fraction of the hydrochloric acid is 0.5% -2%.
Preferably, the impurity removal is to wash with 10-40BV water; the elution is 10-40BV by 70-90% ethanol.
The invention also provides the total alkaloids of the corydalis nepalensis obtained by the preparation method.
The invention also provides application of the corydalis nepalensis total alkaloids in preparing medicines for treating ulcerative colitis.
Preferably, the ulcerative colitis comprises dextran sodium sulfate induced ulcerative colitis.
The invention also provides application of the corydalis nepalensis total alkaloids in preparation of medicines for inhibiting the expression of IL-6, IL-1 beta and TNF-alpha.
The invention also provides application of the corydalis nepalensis total alkaloids in preparation of medicines for promoting IL-10 expression.
The invention also provides application of the corydalis nepalensis total alkaloids in preparation of medicines for promoting SOD release.
The invention also provides application of the total alkaloids of corydalis nepalensis in preparation of medicines for inhibiting MDA and MPO release.
The invention discloses the following technical effects:
the invention provides the effect of the total alkaloids of the corydalis nepalensis for treating ulcerative colitis, the content of the total alkaloids of the corydalis nepalensis prepared by the preparation method can reach 49%, the total alkaloids of the corydalis nepalensis has a good treatment effect on ulcerative colitis of mice induced by Dextran Sodium Sulfate (DSS), and the weight reduction, DAI score reduction, colon length extension and colon tissue inflammation infiltration degree of mice induced by the DSS can be remarkably relieved; regulating biochemical indexes such as inflammation, oxidative stress and the like in colon tissues; has certain regulating effect on intestinal flora.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a graph showing the effect of total alkaloids from corydalis amabilis on body weight of mice in UC model;
FIG. 2 is a graph showing the effect of total alkaloids from corydalis amabilis on the Disease Activity Index (DAI) of mice in UC model;
FIG. 3 is a graph showing the effect of total alkaloids from corydalis amabilis on Colon length (Colon length) of mice with UC model, wherein A is a photograph taken to record Colon length results and B is a length statistics node;
FIG. 4 is a graph showing the effect of total alkaloids from corydalis amabilis on the degree of inflammatory infiltration of colon tissue in mice with UC model;
FIG. 5 shows the effect of total alkaloids from Nepal corydaline on the biochemical index of inflammatory stress in mice in UC model, wherein A-D is the effect of total alkaloids from Nepal corydaline on the biochemical index of inflammatory stress of IL-6, IL-1β, TNF- α and IL-10 in colon tissue of mice in UC model, respectively;
FIG. 6 is a graph showing the effect of total alkaloids from Nepal corydaline on the oxidative stress biochemical index of mice in UC model, wherein A-C are the effects of total alkaloids from Nepal corydaline on the oxidative stress biochemical index of SOD, MDA and MPO in mice in UC model, respectively;
FIG. 7 is a graph showing the effect of total alkaloids from corydalis amabilis on the intestinal flora of mice with UC model.
Detailed Description
Various exemplary embodiments of the invention will now be described in detail, which should not be considered as limiting the invention, but rather as more detailed descriptions of certain aspects, features and embodiments of the invention.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. In addition, for numerical ranges in this disclosure, it is understood that each intermediate value between the upper and lower limits of the ranges is also specifically disclosed. Every smaller range between any stated value or stated range, and any other stated value or intermediate value within the stated range, is also encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.
It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the invention described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from consideration of the specification of the present invention. The specification and examples are exemplary only.
As used herein, the terms "comprising," "including," "having," "containing," and the like are intended to be inclusive and mean an inclusion, but not limited to.
The technical scheme of the invention is conventional in the field, and the reagents or raw materials are purchased from commercial sources or are disclosed.
Example 1
Taking 100g of dry corydalis tuber medicinal material, crushing and sieving to obtain powder, extracting with acidic ethanol with pH=1-2, extracting with ultrasound for 2-4 times, filtering, combining filtrates, and concentrating under reduced pressure to obtain crude extract of the corydalis tuber total alkaloids; dissolving the obtained total alkaloids of the corydalis nepalensis with hydrochloric acid with the mass fraction of 0.5% -2%, and filtering; subjecting the obtained acid liquor to XDA-8 macroporous resin for dynamic adsorption; washing the macroporous resin after adsorption with 10-40BV water, eluting with 70-90% ethanol for 10-40BV, and recovering solvent to obtain the final product. The acid dye colorimetry is combined with the ultraviolet-visible spectrophotometry, berberine is used as a reference substance, and the detection result shows that the content of the total alkaloids of the corydalis nepalensis can reach 49%.
Example 2
1. Ulcerative colitis mice were modeled: after C57BL/6 mice are adaptively fed for one week, 3% DSS solution prepared by freely drinking sterilized water is adopted to induce ulcerative colitis mice model for 7 days, and then the weight change, fecal form and hematochezia degree, colon length, colon tissue pathological change and the like of the mice are used as indexes to verify whether the ulcerative colitis mice model is successfully established.
2. The test method comprises the following steps: 56 healthy male C57BL/6 mice of SPF grade weighing 18-22g were fed adaptively for 7 days, randomly divided into 7 groups: blank (Blank), model (Model), pill (Pill), 5-aminosalicylic acid (5-ASA), high-dose (High), medium (Medium), low-dose (Low) of total alkaloids; the blank group can drink sterilized water freely, the other groups drink sterilized water containing 3% DSS freely every day, other conditions are the same, and the molding day is the administration day; the blank group and the model group are subjected to gastric administration by 0.1mL/10g of body weight to obtain a carrier solvent, the antidiarrheal pill group is subjected to gastric administration by 0.1mL/10g of body weight to obtain an antidiarrheal pill of 200mg/kg/d, the 5-aminosalicylic acid group is subjected to gastric administration by 0.1mL/10g of body weight to obtain 5-ASA of 200mg/kg/d, the high dose group, the medium dose group and the low dose group are subjected to gastric administration by 0.1mL/10g of body weight to obtain a total alkaloids of corydalis nepalensis of 200mg/kg/d, 100mg/kg/d and 50mg/kg/d, the administration is carried out once daily for 7 days, and after the last administration, the administration is fasted for 12 hours without water inhibition. Daily observations recorded the mice weight change, stool morphology and hematochezia levels over 7 days of the experiment.
Mice were sacrificed 7 days after dosing, blood and colon tissues of the mice were collected and processed, and colon length was recorded by photographing; hematoxylin-eosin staining (H & E staining) to observe pathological changes of colon tissue; biochemical indexes such as colon tissue inflammation, oxidative stress and the like are measured by adopting an enzyme-linked immunosorbent assay (ELISA), and the contents of interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF-alpha), interleukin-10 (IL-10), superoxide dismutase (SOD), malonaldehyde (MDA) and Myeloperoxidase (MPO) (wherein IL-6, IL-1 beta, TNF-alpha are pro-inflammatory factor indexes and IL-10 is an anti-inflammatory factor index) are respectively measured according to the specifications of each kit.
Experimental results:
the effect of the total alkaloids from corydalis nepalensis on the body weight of mice in the UC model is shown in fig. 1. From day 5, except for blank groups, obvious weight loss appears in the groups, the weight loss of mice in the model group is most obvious, and the weight loss of each administration group of the total alkaloids of the corydalis nepalensis is relieved, so that the total alkaloids preparation of the corydalis nepalensis for treating ulcerative colitis can obviously relieve the weight loss caused by the ulcerative colitis.
The effect of the total alkaloids from corydalis nepalensis on the Disease Activity Index (DAI) of mice in the UC model is shown in fig. 2. The DAI score table of the UC model mice is shown in Table 1. The mouse DAI score consisted of percent body mass reduction, fecal morphology score, and hematochezia condition score.
The calculation formula is as follows: dai= (percent body mass reduction + fecal morphology fraction + hematochezia condition fraction)/3.
TABLE 1 Disease Activity Index (DAI) score table for ulcerative colitis
Note that: (+) is indicated as "light-duty", (++) is indicated as "heavy-duty".
As can be seen from fig. 2, as the number of administration days increases, each administration group of the nepal corydalis total alkaloids can significantly alleviate the rise of DAI score compared to the model group, indicating that the nepal corydalis total alkaloids preparation for treating ulcerative colitis of the present invention significantly reduces DAI score of UC mice.
As can be seen from fig. 3, compared with the blank group, the colon length of the mice in the model group is significantly shortened, and the administration groups of the total alkaloids of the nepol corydalis are all relieved to a certain extent, which indicates that the preparation of the total alkaloids of the nepol corydalis for treating ulcerative colitis of the invention significantly prolongs the colon length of the mice with UC.
As can be seen from fig. 4, colon tissue of the mice in the blank group had intact mucosa and normal villi, and no inflammatory cell infiltration or mucosal erosion; compared with a blank group, the colon tissue morphology of a model group mouse is obviously changed, a large amount of inflammatory cells infiltrate, the number of goblet cells and crypts is obviously reduced, the submucosal area of the colon is edematous, the cell gap is incomplete, and the barrier of the colon mucosa is seriously damaged; after the treatment of the high-dose group of the total alkaloids of the corydalis nepalensis, the colon tissue morphology of the UC mice is obviously improved, inflammatory cell infiltration is obviously reduced, and the intestinal mucosa barrier is relatively complete. Thus, the total alkaloid preparation of the corydalis nepalensis for treating ulcerative colitis obviously reduces the inflammatory infiltration degree of colon tissues caused by the ulcerative colitis.
As can be seen from fig. 5, each of the administered groups of the total alkaloids of nepal corydalis had significantly inhibited the release of pro-inflammatory factors IL-6, IL-1β and TNF- α, and exhibited dose dependency, with the high dose group of total alkaloids of nepal corydalis having the best inhibitory effect, relative to the model group; compared with the model group, each administration group of the total alkaloids of the Nepal can obviously promote the release of the anti-inflammatory factor IL-10, and the dose dependence is presented, wherein the high-dose group of the total alkaloids of the Nepal has the best promoting effect. Therefore, the total alkaloids of the corydalis nepalensis prepared by the preparation method can play a role of medicine by inhibiting pro-inflammatory factors and promoting the release of anti-inflammatory factors, and the total alkaloids of the corydalis nepalensis for treating ulcerative colitis can obviously relieve the unbalance of inflammatory stress biochemical indexes caused by the ulcerative colitis.
As can be seen from fig. 6, the administration groups of the total alkaloids of the corydalis nepalensis can promote SOD and inhibit the release of MDA and MPO, thereby acting in comparison with the blank group and the model group. The invention shows that the preparation of the total alkaloids of the corydalis nepalensis for treating ulcerative colitis can obviously relieve the oxidative stress biochemical index imbalance caused by the ulcerative colitis.
As can be seen from fig. 7, the total alkaloids preparation of nepal corydaline plays a therapeutic role by adjusting the ratio of harmful and beneficial flora in the intestinal tract of mice, which indicates that the total alkaloids preparation of nepal corydaline for treating ulcerative colitis can significantly adjust the intestinal flora imbalance caused by ulcerative colitis.
In conclusion, the total alkaloids of the corydalis nepalensis prepared by the preparation method can obviously relieve the weight reduction of mice with ulcerative colitis induced by DSS, reduce DAI score, prolong colon length and reduce inflammatory infiltration degree of colon tissues; regulating biochemical indexes such as inflammation, oxidative stress and the like in colon tissues; regulating intestinal flora.
The above embodiments are only illustrative of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention, and various modifications and improvements made by those skilled in the art to the technical solutions of the present invention should fall within the protection scope defined by the claims of the present invention without departing from the design spirit of the present invention.
Claims (10)
1. A preparation method of the total alkaloids of the corydalis nepalensis is characterized by crushing and extracting the corydalis nepalensis medicinal materials, concentrating the extracting solution to obtain an extract, and dissolving, filtering, enriching and purifying the obtained extract by using acid liquor to obtain a purified product of the total alkaloids of the corydalis nepalensis.
2. The method of manufacturing according to claim 1, comprising the steps of:
(1) Pulverizing and sieving herba corydalis Bungeanae medicinal materials to obtain powder, ultrasonic extracting for 2-4 times, filtering, mixing filtrates, and concentrating under reduced pressure to obtain crude extract of herba corydalis Bungeanae;
(2) Dissolving the crude extract of corydalis nepalensis with hydrochloric acid, and filtering to obtain an acidic solution;
(3) Dynamically adsorbing the acidic solution by using macroporous resin XDA-8;
(4) Removing impurities from the macroporous resin after the adsorption is finished, eluting, and recovering the solvent to obtain the final total alkaloids of the corydalis nepalensis.
3. The preparation method according to claim 2, wherein the mass fraction of the hydrochloric acid is 0.5% -2%.
4. A method according to claim 2 or 3, wherein the impurity removal is an impurity removal by washing with 10-40BV water; the elution is 10-40BV by 70-90% ethanol.
5. The total alkaloids of corydalis amabilis obtained by the process according to any one of claims 1-4.
6. The use of the total alkaloids from corydalis amabilis according to claim 5 for the preparation of a medicament for the treatment of ulcerative colitis.
7. The use of the total alkaloids of corydalis amabilis according to claim 5 for the preparation of a medicament for inhibiting the expression of IL-6, IL-1 β and TNF- α.
8. The use of the total alkaloids of corydalis amabilis according to claim 5 for the preparation of a medicament for promoting the expression of IL-10.
9. The use of the total alkaloids of corydalis amabilis according to claim 5 for the preparation of a medicament for promoting the release of SOD.
10. The use of the total alkaloids of corydalis amabilis according to claim 5 for the preparation of a medicament for inhibiting the release of MDA and MPO.
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