CN103223058B - Fructus Viticis Negundo total flavone extract, and preparation method and medicinal uses thereof - Google Patents
Fructus Viticis Negundo total flavone extract, and preparation method and medicinal uses thereof Download PDFInfo
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- CN103223058B CN103223058B CN201310169292.7A CN201310169292A CN103223058B CN 103223058 B CN103223058 B CN 103223058B CN 201310169292 A CN201310169292 A CN 201310169292A CN 103223058 B CN103223058 B CN 103223058B
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Abstract
The invention provides a Fructus Viticis Negundo total flavone extract, and a preparation method and medicinal uses thereof. The preparation method comprises the following steps: 1, taking Fructus Viticis Negundo, carrying out reflux extraction through using water or alcohol or an alcohol-water solution as an extraction solvent twice, mixing the obtained extraction liquid to obtain an extract liquid mixture, and carrying out vacuum concentration of the mixture; and 2, carrying out polyamide resin column chromatography of a concentrate obtained in step 1, eluting with water to remove impurities, eluting with the alcohol or the alcohol-water solution, and collecting the obtained eluate to obtain the Fructus Viticis Negundo total flavone extract. The invention also provides applications of the Fructus Viticis Negundo total flavone extract in the preparation of medicines for preventing and treating asthma, the chronic obstructive pulmonary disease, the chronic bronchitis or cold coughs.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of Fructus Viticis Cannabifoliae extractive of general flavone and preparation method thereof and medical usage, the more specifically application of Fructus Viticis Cannabifoliae extractive of general flavone in preparation prevention and treatment asthma, chronic obstructive pulmonary disease, chronic bronchitis or cold cough medicine.
Background technology
Bronchial asthma is chronic respiratory tract disease the most common in world wide.At present, global asthmatic patient approximately 300,000,000 people, Chinese patients with asthma approximately 3,000 ten thousand.In recent years, because of its prevalence and mortality rate all in rising trend, become serious public health problem and received the very big concern of countries in the world.Therefore need to provide medicine and the method for effectively treating asthma.
At present the treatment of asthma is not also had to specific drug.Clinical treatment mainly be take application bronchodilator as main, has β
2-adrenergic aceptor antagonist class, alpha-adrenergic aceptor antagonist class, aminophylline class, cholinoceptor antagonist class, calcium ion antagonist class, potassium-channel agonist, glucocorticoid (ICS), cell membrane stability agent, antihistamine drug, LTRA, platelet activating factor antagonist, specific active immunotherapy agent, Nonspecific immunotherapy for bronchus agent etc.Nineteen ninety-five has been put into effect the application that " GINA " further promoted and popularized glucocorticoid.These Therapeutic Method are to relieving asthma symptoms, and there is certain effect the quality of life of improving asthma patient, but do not make the M & M of asthma decrease, and are on the contrary the trend increasing year by year.Treatment asthma needs more effective and safer medicine.
The pathogenesis of chronic obstructive pulmonary disease is not yet completely clear, generally believes that at present take air flue, pulmonary parenchyma and pulmonary vascular chronic inflammatory disease is feature.Clinical employing long-term inhaled glucocorticoid therapy anti-inflammatory treatment and suction β
2the bronchodilators such as-3 adrenergic receptor agonists, cholinoceptor antagonist are treated.But the therapeutic effect of these medicines is not very good, the medicine of finding more effective treatment chronic obstructive pulmonary disease is very important.
Fructus Viticis Cannabifoliae is the fruit with Constellation calyx of Verenaceae perennial plant Herba Viticis Cannabifoliae Vitex negundo L.var.cannabifolia (sieb.Et Zucc) Hand.Mazz, also be little Fructus Viticis Cannabifoliae, < < Chinese medicine voluminous dictionary > >, < < Compendium of Materia Medica > > all record " Fructus Viticis Cannabifoliae bitter in the mouth, temperature; nontoxic, main except cold and heat between bone, tonneau gastric qi, cough-relieving are contrary, the therapeutic method to keep the adverse QI flowing downwards." there is expelling phlegm for arresting cough, relieving asthma and regulate the flow of vital energy and the effect of pain relieving.Document is recorded, and Vitex species mainly contains the number of chemical compositions such as flavonoid, Diterpenes, iridoids, triterpenes.
Less to studying to Fructus Viticis Cannabifoliae extractive of general flavone at present, the research > > (Xiao Guozhen etc. of document < < Fructus Viticis Cannabifoliae ethanol extraction antioxidant activity, Guangdong University of Technology's journal, in JIUYUE, 2006, the 23rd the 3rd phase of volume, 31-35) a kind of preparation method of Fructus Viticis Cannabifoliae ethanol extraction is disclosed, Fructus Viticis Cannabifoliae is dried 3h through 75 ℃, pulverized 40 mesh sieves, weighing 100g puts in conical flask, add 250ml ethanol, in thermostat water bath, 60 ℃～65 ℃ are extracted 60h, and stir at any time, leach leaching liquid distilling under reduced pressure concentrated, vacuum drying, obtain paste extract, in extractum, general flavone content is 11.52%.
In this extract, flavones content is lower, complicated component, and its activity research is only rested on to antioxidant activity aspect, clinical pharmacology has little significance, and there is no clear and definite pharmacologically active report.
Summary of the invention
The object of this invention is to provide a kind of Fructus Viticis Cannabifoliae extractive of general flavone and preparation method thereof and the application in preparation prevention and treatment asthma, chronic obstructive pulmonary disease, chronic bronchitis or cold cough medicine.
Fructus Viticis Cannabifoliae extractive of general flavone provided by the present invention extracts from Chinese medicine Fructus Viticis Cannabifoliae, and described Fructus Viticis Cannabifoliae is the fruit of Verbenaceae Herba Viticis Cannabifoliae.
The concrete technical scheme of the present invention is as follows:
A preparation method for Fructus Viticis Cannabifoliae extractive of general flavone, is characterized in that comprising the steps:
(1) get Fructus Viticis Cannabifoliae, water or alcohol or alcohol-water solution extract 2 times as extracting solvent refluxing, merge extractive liquid,, vacuum concentration;
(2) by the concentrated solution polyamide column chromatography of step (1), first wash decontamination with water and with alcohol or alcohol-water solution, carry out eluting again, collect eluent, obtain Fructus Viticis Cannabifoliae extractive of general flavone.
Above-mentioned preparation method, the described alcohol particular methanol of step (1), ethanol or isopropyl alcohol, the aqueous solution of described alcohol-water solution particular methanol, ethanol or isopropyl alcohol, further in preferred alcohols aqueous solution, the percent by volume of alcohol is 70%.
Above-mentioned preparation method, in step (1), also available other solvent extracts preparation as acetone etc.
Above-mentioned preparation method, crosses 10 mesh sieves after preferably Fructus Viticis Cannabifoliae being pulverized and extract in step (1).
Above-mentioned preparation method, is preferably used 70% alcohol reflux 2 hours in step (1), extracts altogether twice, preferably by extracting solution vacuum concentration to without alcohol taste.
Above-mentioned preparation method, described in step (2), polyamide selects preferred 60-100 order.
Above-mentioned preparation method, the described alcohol particular methanol of step (2), ethanol or isopropyl alcohol, the aqueous solution of described alcohol-water solution particular methanol, ethanol or isopropyl alcohol, further in preferred alcohols aqueous solution, the percent by volume of alcohol is 70%.
Above-mentioned preparation method, the method for optimizing of step (2): add sample liquid with 2 times of column volume loading flow velocitys hourly and carry out dynamic adsorption.First with the distilled water eluting of 4 times of column volumes, remove impurity, discard water elution liquid.70% alcoholic solution with 5 times of column volumes carries out eluting again, collects ethanol elution, and vacuum concentration is to dry, and obtaining general flavone content in Fructus Viticis Cannabifoliae extractive of general flavone is 83.72%.
The present invention also provides a kind of Fructus Viticis Cannabifoliae extractive of general flavone, adopts above-mentioned preparation method to prepare, and wherein general flavone content is 83.72%.
The present invention also provides the application of above-mentioned Fructus Viticis Cannabifoliae extractive of general flavone in preparation prevention and treatment asthma, chronic obstructive pulmonary disease, chronic bronchitis or cold cough medicine.
The features such as the present invention confirms by experiment, and it is active that Fructus Viticis Cannabifoliae extractive of general flavone of the present invention has treatment asthma, treatment chronic obstructive pulmonary disease (COPD), treatment chronic bronchitis, antiallergic pharmacology, has toxicity little, and life-time service curative effect is better.
Fructus Viticis Cannabifoliae total flavones provided by the invention, can mix with one or more pharmaceutically acceptable carrier components, containing in the pharmaceutical composition of Fructus Viticis Cannabifoliae total flavones, further contains β
2-3 adrenergic receptor agonists.
Application of the present invention, Fructus Viticis Cannabifoliae extractive of general flavone can with the form of single medicine by administration or can with other medicines administering drug combinations.
Fructus Viticis Cannabifoliae extractive of general flavone of the present invention can be used separately or use with the form of pharmaceutical composition.Pharmaceutical composition comprises compound or pharmaceutically acceptable salt thereof of the present invention and the pharmaceutically suitable carrier as active component.Preferably, pharmaceutical composition of the present invention has the Fructus Viticis Cannabifoliae extractive of general flavone of the present invention as active component of 0.1-99.9% percentage by weight." pharmaceutically suitable carrier " can not destroy the pharmaceutical active of compound or pharmaceutically acceptable salt thereof of the present invention, its effective dose simultaneously, and can playing pharmaceutical carrier, to make the consumption of used time nontoxic to human body.
" pharmaceutically suitable carrier " includes but not limited to: ion exchange material, aluminium oxide, aluminium stearate, lecithin, self-emulsifying drug delivery system (SEDDS) is as d-TPGS 1000, the surfactant that the pharmaceutical preparatioies such as tween or other similar polymerisation mediums are used, serum albumin is as human serum albumin, buffer substance is as phosphate, glycine, sorbic acid, potassium sorbate, saturated vegetable fatty acid partial glyceride mixes, water, salt, electrolyte is as sulfate protamine, sodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salt, silica gel, magnesium silicate etc.Polyvidon, cellulosic material, polyvinyl alcohol, sodium carboxymethyl cellulose, polyacrylate, ethylene-polyoxyethylene-block polymer and lanoline, cyclodextrin as α-, β-, gamma-cyclodextrin or its derivant through chemical modification all can be used for promoting the drug delivery of compound of the present invention, its pharmaceutical salts or prodrug as the hydroxyalkyl cyclodextrin such as 2-and 3-HP-β-CD or other soluble derivatives etc.
Other pharmaceutically acceptable auxiliaries also can add in pharmaceutical composition of the present invention as filler (as Lactis Anhydrous, starch, lactose beadlet and glucose), binding agent (as microcrystalline Cellulose), disintegrating agent (as crosslinked carboxymethyl fecula sodium, cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose and cross-linked pvp), lubricant (as magnesium stearate), absorption enhancer, flavouring agent, sweeting agent, diluent, excipient, wetting agent, solvent, solubilizing agent and coloring agent etc.
The Fructus Viticis Cannabifoliae extractive of general flavone of the invention described above and pharmaceutical composition can pass through intestinal or parenteral route administration.Non-intestinal drug delivery agent comprises injection, cream, ointment, patch, spray etc.That route of administration comprises is subcutaneous, in Intradermal, intra-arterial, intravenous, intramuscular, intraarticular, synovial fluid, in breastbone, in sheath, intralesional, intracranial injection or infusion, or, oral, local, rectum, per nasal, through cheek, vagina, Sublingual, Intradermal, mucosa, trachea, urethra administration, or by sucking aerosol or implantation is accumulated or the administration of acupuncture mode.
The Fructus Viticis Cannabifoliae extractive of general flavone of the invention described above and the treatment effective dose of pharmaceutical composition are between 0.5mg/kg – 100mg/kg, can be used for the single drug of relevant disease or drug combination treatment, the scope that can understand for those skilled in the art.
Accompanying drawing explanation
Fig. 1 is the result figure of Fructus Viticis Cannabifoliae extractive of general flavone of the present invention to isolated guinea pig ileum test
The specific embodiment
Concrete steps of the present invention are described by the following examples, but not limited by embodiment.
The term that used in the present invention, except as otherwise noted, generally has the implication that those of ordinary skills understand conventionally.
Below in conjunction with specific embodiment comparable data, the present invention is described in further detail.Should be understood that these embodiment just in order to demonstrate the invention, but not limit the scope of the invention by any way.
In following examples, various processes and the method do not described in detail are conventional methods as known in the art.
The preparation of embodiment 1 Fructus Viticis Cannabifoliae extractive of general flavone
Get Fructus Viticis Cannabifoliae 10kg, after pulverizing, cross 10 mesh sieves, by 70% ethanol 60L reflux, extract, 2 hours, leaching extracting solution, medicinal residues add 70% ethanol 45L reflux, extract, 2 hours, leaching extracting solution again, merge extractive liquid,, vacuum concentration, to without alcohol taste, adds water 2L stirring and dissolving and makes sample solution.
Adopt conventional method to process polyamide 60-100 order (being purchased from the biochemical plastic molding and processing plant of Taizhou road and bridge tetramethyl), get the polyamide 2.5Kg dress post (200mm * 1000mm) of handling well, with 2 times of column volume loading flow velocitys hourly, add sample liquid and carry out dynamic adsorption, add altogether sample solution 1L.First with the distilled water eluting of 4 times of column volumes, remove impurity, discard water elution liquid.70% ethanol with 5 times of column volumes carries out eluting again, collects ethanol elution, and vacuum concentration, to dry, obtains Fructus Viticis Cannabifoliae extractive of general flavone 0.24kg.Through spectrophotometry general flavone content, be 83.72%.
Embodiment 2 ammonia draw coughs test
40 of mices, are divided into dosage group (200mg/kg), Fructus Viticis Cannabifoliae extractive of general flavone low dose group (100mg/kg) in matched group, Fructus Viticis Cannabifoliae extractive of general flavone high dose group (400mg/kg), Fructus Viticis Cannabifoliae extractive of general flavone, 10 every group at random.After gastric infusion, 1h starts experiment.Get 1 mice at every turn, put into the bell glass that volume is 1L, inside put a filter paper (2 * 2cm
2), the ammonia of 0.3ml is dripped on filter paper, make mice at bell glass internal stimulus 30s, after taking-up, observe immediately and record the incubation period of mice 2min interior cough number of times and cough, the abdominal muscle contraction that shows as of mouse cough is dehisced.After gavage 3h, repeat to test 1 time, observe and record.
The mouse cough inhibitory action that table 1 Fructus Viticis Cannabifoliae extractive of general flavone causes ammonia
Note: * P < 0.001 has significantly or highly significant difference.
Experimental result is as shown in table 1, and three dosage groups of Fructus Viticis Cannabifoliae extractive of general flavone all can significantly suppress the mouse cough number of times that ammonia causes and extend the incubation period of cough, and action intensity and dosage effect are proportionate.Compare with matched group, have significantly or highly significant difference.
Embodiment 3 acecolines add histamine phosphate salt and suck to draw and breathe heavily test
Get 40 of 200-250g Cavia porcelluss, male and female half and half, are placed in the airtight glass beaker of 5000mL volume, with ultrasound atomizer spray 1% acecoline and 0.2% histamine phosphate salt isometric(al) mixed liquor 10s.Take out immediately Cavia porcellus, observe drawing of Cavia porcellus and breathe heavily incubation period (from spraying, starting to be the devil to asthma attack, breathing, until the time of twitching and falling).Then Cavia porcellus is divided at random to dosage group (200mg/kg), Fructus Viticis Cannabifoliae extractive of general flavone low dose group (100mg/kg) in matched group, Fructus Viticis Cannabifoliae extractive of general flavone high dose group (400mg/kg), Fructus Viticis Cannabifoliae extractive of general flavone, 10 every group.After administration, 1h and 3h draw and breathe heavily respectively, observe to draw and breathe heavily incubation period.Within two minutes, not breathing heavily above person draws and breathes heavily incubation period in 120s.
Table 2 Fructus Viticis Cannabifoliae extractive of general flavone draws on medicine the impact that Cavia porcellus breathes heavily
Note: * P<0.001 has significant difference.
Result of the test is as shown in table 2, three dosage groups of Fructus Viticis Cannabifoliae extractive of general flavone are the tic incubation period of energy significant prolongation Cavia porcellus all, comparing difference with blank group has significant, shows that Fructus Viticis Cannabifoliae extractive of general flavone has significant antiasthmatic effect, and its increase acting on dosage strengthens.
Embodiment 4 isolated guinea pig ileum tests
Get 300g left and right Cavia porcellus, its head is struck to dusk, arterial blood letting is put to death.Get one section, the ileum of about 6ml left and right, hang in the Magnus' bath that fills tyrode's solution, 37 ± 0.5 ℃ of constant temperature, one end ties up on L-type breather, is fixed, from the logical people's oxygen in bath bottom, a 15-20 per minute bubble, the other end is fixed on preset load 2g on pressure transducer, after balance 30min, traces normal myenteron shrinkage curve.With acetylcholine (1 * 10
-3g/L) shrinkage curve in contrast, rinses 3 times, adds Fructus Viticis Cannabifoliae extractive of general flavone (10 * 10 of the present invention
-3g/L) effect adds the acetylcholine of equivalent after 5 minutes, trace shrinkage curve and with control curve comparison, result is (impact of A. acetylcholine on ileum, B. Fructus Viticis Cannabifoliae total flavones effect acetylcholine impact on ileum after 5 minutes) as shown in Figure 1.Result shows that Fructus Viticis Cannabifoliae extractive of general flavone of the present invention can significantly alleviate the Contraction of The Ileum From A White reaction that acetylcholine causes.
Claims (1)
1. the application of the Fructus Viticis Cannabifoliae extractive of general flavone that a general flavone content is 83.72% in preparation prevention and treatment asthma, chronic obstructive pulmonary disease, chronic bronchitis or cold cough medicine.
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Non-Patent Citations (3)
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| 微波法提取牡荆总黄酮的研究;黄琼，等;《安徽农业科学》;20110630;第39卷(第18期);第10857、10921 * |
| 牡荆属植物的化学成分及其药理作用与临床应用;刘树根，等;《江西医药》;19841231(第6期);第40-49页 * |
| 黄琼，等.微波法提取牡荆总黄酮的研究.《安徽农业科学》.2011,第39卷(第18期),第10857、10921页. * |
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