CN101524488B - Preparation method of compound bamboo leave flavone dripping pill - Google Patents
Preparation method of compound bamboo leave flavone dripping pill Download PDFInfo
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- CN101524488B CN101524488B CN2009100979054A CN200910097905A CN101524488B CN 101524488 B CN101524488 B CN 101524488B CN 2009100979054 A CN2009100979054 A CN 2009100979054A CN 200910097905 A CN200910097905 A CN 200910097905A CN 101524488 B CN101524488 B CN 101524488B
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Abstract
The invention discloses a preparation method of compound bamboo leave flavone dripping pill, belonging to the technical field of traditional Chinese medicine preparation. In the dripping pill preparation, Chinese herbal medicine bamboo leaves and mimosa are used as raw materials, a flavone extractive is obtained by extracting according to a certain method, and then the flavone extractive and pharmaceutical accessories used as matrix are processed by a certain method in proportion to prepare the final product. The dripping pill has the characteristics of high bioavailability, quick dissolution time, fast absorption by oral taking, high content of effective ingredients, accurate dosage, and convenient taking and carrying; the invention also has the functions of anti-lipid overoxidation, free radical removal, blood fat and cholesterolemia reduction, coronary blood flow increase, and myocardial ischemia melioration, and can be used for resisting oxidation, resisting aging, lowering blood fat, preventing and curing arteriosclerosis, cerebral ischemia, miocardial infarction and other diseases as well as the adjuvant therapy for cancer.
Description
Technical field
The invention belongs to the Chinese medicinal preparation method technical field, be specially the preparation method of compound bamboo leave flavone dripping pill.
Background technology
Diseases such as hyperlipidemia, hypercholesterolemia, arteriosclerosis are the chronic diseases in the modern society, it can cause diseases such as coronary heart disease, myocardial infarction, cardiac sudden death, hypertension, diabetes, and these diseases are to cause the lethal one of the main reasons of middle-aged and elderly people in recent years.Therefore exploratory development Chinese medicine is to above treatment of diseases and the Chinese medicine with remarkable clinical efficacy is carried out the novel form exploitation have far reaching significance.But after taking, present most of oral preparation of Chinese traditional medicinal has shortcomings such as molten diffusing time length, dissolution and bioavailability are low.
The natural flavone compounds is one of important physical active substance in the plant, it can not only be as the medicine that prevents cardiovascular and cerebrovascular disease, and physiologically actives such as tangible anti peroxidation of lipid, defying age, removing free radical, blood fat reducing, immunomodulating are arranged, it is the medicine that wide application prospect is arranged in the control of a kind of nutrition the mankind, health and old degenerative disease, it also is the application prospect Natural antioxidant widely, the resistant activity oxygen-derived free radicals can be used for developing the plurality kinds of health care foods and cosmetics.
Its property of Folium Bambusae is light, little puckery, destitute, has clearing heat and relieving fidgetness, a diuresis of quenching one's thirst, the detoxifcation that makes eye bright, and antioxidation, blood fat reducing, increase coronary flow, improves the effect of aspects such as myocardial ischemia.Contain a large amount of active substances in the Folium Bambusae, comprise flavonoid, triterpenes, phenolic acids, anthraquinone class, Coumarins, amino acids and other trace element the human body beneficial.Folium Bambosae flavone is the main component that wherein activity is outstanding, content is abundant.Mainly contain flavone c-glycoside in the Folium Bambusae total flavones, comprise orientin, Lutonaretin, apigenin-8-C-glucoside, Saponaretin etc.Studies show that, the Folium Bambosae flavone glycoside has many-sided biological activity, as antioxidation, defying age, removing free radical, blood fat reducing and cholesterolemia, the coronary artery dilating flow, improve myocardial ischemia, reduce platelet aggregation, resist myocardial infarction, improve cerebral ischemia, the function of aspects such as antitumor and immunological enhancement.Folium Bambosae flavone can not only and can be used for developing plurality kinds of health care foods and cosmetics etc. as the medicine of control cardiovascular and cerebrovascular disease.
Herba Mimosae Pudicae has clearing away heat and promoting diuresis, preventing phlegm from forming and stopping coughing, blood fat reducing, improves effects such as myocardial ischemia.Mainly contain compositions such as flavonoid, phenolic acids, triterpenes in the Herba Mimosae Pudicae, wherein flavone compound is a main component.The Herba Mimosae Pudicae flavone than multicomponent in especially with orientin, Lutonaretin, apigenin-8-C-glucoside, Saponaretin, 5,7,3 ', 4 '-tetrahydroxy-8-C-[α-L-rhamnose-(1 → 2)]-β-D-glucoside, 5,7,3 ', 4 '-tetrahydroxy-8-C-[β-D-celery sugar-(1 → 4)]-content of β-D-glucoside is higher and active outstanding.Studies show that above flavonoid glycoside has certain anti peroxidation of lipid, removes free radical, antitumor, blood fat reducing, blood sugar lowering, many-sided effect such as anti-inflammation, antiviral, raise immunity.
Orientin, Lutonaretin, apigenin-8-C-glucoside, Saponaretin, structural formula is as follows:
The orientin Lutonaretin
The apigenin-8-C-glucoside Saponaretin
Summary of the invention
In view of the above-mentioned problems in the prior art, the object of the present invention is to provide a kind of technical scheme of preparation method of compound bamboo leave flavone dripping pill, the flavone dripping pill active constituent content height that makes, can be used for antioxidation, anti-aging, blood fat reducing, prevent and treat treatment of diseases such as arteriosclerosis, cerebral ischemia and myocardial infarction, also can be used for assistant treating cancer.
The preparation method of described compound bamboo leave flavone dripping pill is characterized in that comprising following processing step:
1) gets 6～8 parts of Folium Bambusaes and 2～4 portions of Herba Mimosae Pudicaes as medicinal raw material, be ground into coarse powder after the mixing, cross 20～60 mesh sieves, medicinal material coarse powder is measured 50～70% aquiferous ethanol supersound extraction 2～3 times with 6～10 times at 50 ℃ down at every turn, each 30～60min, sucking filtration, merging filtrate;
2) filtrate is concentrated into 1/3～1/5 of original volume at 50 ℃ of following vacuum films of bath temperature, obtain concentrated solution, with concentrated solution powdered active carbon ultrasonic 20～30min under 50 ℃, the consumption of powdery active carbon is a medicinal raw material dry weight 1～2%, remove activated carbon, filtrate continuation is concentrated to 1/8～1/12 of original volume at vacuum film below 50 ℃, obtains concentrated solution once more;
3) with step 2) in the concentrated solution that obtains once more with n-butanol extraction 4 times, preceding 2 each consumptions are 1～1.5 times of amount of concentrated solution volume, 1/2～2/3 times of amount that 2 the each consumptions in back are the concentrated solution volume, combining extraction liquid becomes paste at vacuum concentration below 50 ℃;
4) be dissolved in the low amounts of water concentrating paste behind the n-butanol extraction, by macroporous adsorptive resins, the blade diameter length ratio of chromatographic column is 1: 10～15, uses H earlier
2O and 10% aquiferous ethanol eluting are removed water-solubility impurity, carry out gradient elution with 15～65% aquiferous ethanol more than three kinds or three kinds successively again, all use 70% aquiferous ethanol eluting to remove all dirt at last, the regeneration macroporous adsorbent resin, above elution flow rate is 10～15mLmin
-1Collect each position eluent of 3 times of column volumes respectively, merge each position eluent of 20～60% aquiferous ethanol, it is that 1.2～1.3 thick paste or vacuum drying become dry powder that the eluent that merges is become relative density at vacuum concentration below 50 ℃, promptly gets the compound bamboo leave flavone extract;
5) mixed-matrix is by two kinds of matrix group resulting mixtures in Macrogol 4000, polyethylene glycol 6000, carboxymethyl starch sodium, the poloxamer, and two kinds of substrate are according to the fusion of 1: 1～1: 10 mixed post-heating of weight ratio; The compound bamboo leave flavone extract that makes in the step 4) is pulverized the back cross 200 mesh sieves, add in the fused mixed-matrix and stir, the weight ratio of extractive of general flavone and mixed-matrix is 1: 2～1: 5, the fused solution that makes 70～80 ℃ of insulations 20～30 minutes so that arranged wherein air bubble, standby;
6) place the drop pill machine to make drop pill the fused solution that makes in the step 5), be drying to obtain compound bamboo leave flavone dripping pill.
The preparation method of described compound bamboo leave flavone dripping pill, it is characterized in that in the step 1): the weight ratio of medicinal raw material is 7～8 parts of Folium Bambusaes, 3～2 portions of Herba Mimosae Pudicaes, measure 60～70% aquiferous ethanol supersound extraction, each 40～55min, preferred 45～50min with 7～8 times at every turn.
The preparation method of described compound bamboo leave flavone dripping pill is characterized in that step 2) in: ultrasonic time is 25～28min, and sucking filtration is removed activated carbon, obtains filtrate continuation and is concentrated to 1/9～1/10 of original volume.
The preparation method of described compound bamboo leave flavone dripping pill is characterized in that in the step 4): described macroporous adsorptive resins is a Diaion HP-20 macroporous adsorptive resins, and the blade diameter length ratio of chromatographic column is 1: 10～12, uses H earlier
2O and 10% aquiferous ethanol eluting are removed water-solubility impurity, carry out gradient elution with 20% aquiferous ethanol, 40% aquiferous ethanol, 60% aquiferous ethanol successively again, all use 70% aquiferous ethanol eluting to remove all dirt at last, the regeneration macroporous adsorbent resin, above elution flow rate is 12～14mLmin
-1, collect each position eluents of 3 times of column volumes respectively, merge each position eluent of 20～60% aquiferous ethanol.
The preparation method of described compound bamboo leave flavone dripping pill, it is characterized in that in the step 5): mixed-matrix is a kind of and Macrogol 4000 in carboxymethyl starch sodium, the poloxamer, a kind of composition in the polyethylene glycol 6000, the weight ratio of two kinds of substrate 1: 3～1: 8, preferred 1: 5～1: 6.
The preparation method of described compound bamboo leave flavone dripping pill is characterized in that in the step 5): the weight ratio of extractive of general flavone and mixed-matrix is 1: 3～1: 4, and fused solution was 72～75 ℃ of insulations 22～25 minutes.
The preparation method of described compound bamboo leave flavone dripping pill, it is characterized in that in the step 6): the water dropper temperature constant temperature to 70 of drop pill machine～80 ℃, the temperature of coolant remains on 6～10 ℃, the fluid reservoir that fused solution is placed the drop pill machine drip apart from be 5～7cm, to drip speed be to splash into coolant under 20～60 droplets/minute the condition, is condensed into ball; Taken out by the drop pill of drop pill machine exit with molding, the coolant on filtering surface is put and is drying to obtain compound bamboo leave flavone dripping pill in the vacuum drying oven.
The preparation method of described compound bamboo leave flavone dripping pill, it is characterized in that in the step 6): the water dropper temperature constant temperature to 75 of drop pill machine～78 ℃, the temperature of coolant remains on 7～8 ℃, and dripping distance is that 5.5～6cm, a speed are 30～50 droplets/minute, preferred 40～45 droplets/minute.
The preparation method of described compound bamboo leave flavone dripping pill is characterized in that in the step 6): described coolant is a kind of in liquid paraffin, soybean oil, the methyl-monosilane.
The preparation method of above-mentioned compound bamboo leave flavone dripping pill, with Folium Bambusae total flavones and Herba Mimosae Pudicae total flavones is main component, mixing pharmaceutic adjuvant is that compatibility substrate is made the oral administration solid dispersant according to certain ratio and method, all contain important activity composition orientin, Lutonaretin, apigenin-8-C-glucoside, Saponaretin in main component Folium Bambusae total flavones and the Herba Mimosae Pudicae total flavones, its preparation method is simple, and working condition is controlled easily, the automaticity height, save great amount of manpower, the production efficiency height.This drop pill bioavailability height, dissolve scattered time limit is fast, and buccal absorbs rapidly, has efficient quick-acting effect; The volume of drop pill is little, and is easy to use and carry; The active constituent content height, wherein the content of orientin is 5.3%～8.8%, and the content of Lutonaretin is 4.7%～6.2%, and the content of apigenin-8-C-glucoside is 2.4%～5.6%, and the content of Saponaretin is 1.3%～5.1%; The ball method of double differences is different little, and content of effective is accurate, and quality is convenient to control, and the dosage of drop pill is accurate, controls taking dose easily.This dropping pill formulation can be used for antioxidation, anti-aging, blood fat reducing, prevents and treats treatment of diseases such as arteriosclerosis, cerebral ischemia and myocardial infarction, also can be used for assistant treating cancer.The percentage composition that relates in the present specification, except other had explanation, the percentage composition of liquid was a volume ratio, solid percentage composition is a weight ratio.
Description of drawings
Fig. 1 is the HPLC collection of illustrative plates of reference substance; Fig. 2 is the HPLC collection of illustrative plates of test sample;
Among the figure: 1-Lutonaretin, 2-orientin, 3-apigenin-8-C-glucoside, 4-Saponaretin.
The specific embodiment
The preparation method of compound bamboo leave flavone dripping pill of the present invention is implemented by following concrete technical scheme.
Embodiment 1
1) get 7 parts of Folium Bambusaes and 3 portions of Herba Mimosae Pudicaes as medicinal raw material, be ground into coarse powder after the mixing, cross 40 mesh sieves, with medicinal material coarse powder 50 ℃ of each down aquiferous ethanol supersound extraction with 8 times of amounts 60% 3 times, 45min at every turn, sucking filtration, merging filtrate;
2) filtrate is concentrated into 1/4 of original volume at 50 ℃ of following vacuum films of bath temperature, obtain concentrated solution, with concentrated solution powdered active carbon ultrasonic 25min under 50 ℃, the consumption of powdered active carbon is 1.5% of a medicinal raw material dry weight, sucking filtration, remove activated carbon, filtrate continuation is concentrated to 1/10 of original volume at vacuum film below 50 ℃, obtains concentrated solution once more;
3) with step 2) in the concentrated solution that obtains once more with n-butanol extraction 4 times, preceding 2 each consumptions are 1.2 times of amounts of concentrated solution volume, back 2 each consumptions are 1/2 times of amount of concentrated solution volume, combining extraction liquid becomes paste at vacuum concentration below 50 ℃;
4) be dissolved in the low amounts of water concentrating paste behind the n-butanol extraction, by Diaion HP-20 macroporous adsorptive resins, the blade diameter length ratio of chromatographic column is 1: 12, uses H earlier
2O and 10% aquiferous ethanol eluting are removed water-solubility impurity, carry out gradient elution with 20% aquiferous ethanol, 40% aquiferous ethanol, 60% aquiferous ethanol successively again, all use 70% aquiferous ethanol eluting to remove all dirt at last, the regeneration macroporous adsorbent resin, above elution flow rate is 12mLmin
-1Collect each position eluent of 3 times of column volumes respectively, merge 20% aquiferous ethanol, 40% aquiferous ethanol, each position eluent of 60% aquiferous ethanol, it is that 1.25 thick paste or vacuum drying become dry powder that the eluent that merges is become relative density at vacuum concentration below 50 ℃, promptly gets the compound bamboo leave flavone extract;
5) mixed-matrix is that 1: 1 Macrogol 4000 and polyethylene glycol 6000 are formed by weight ratio, and two kinds of substrate are mixed the post-heating fusion; The compound bamboo leave flavone extract that makes in the step 4) is pulverized the back cross 200 mesh sieves, add in the fused mixed-matrix and stir, the weight ratio of extractive of general flavone and mixed-matrix is 1: 3, the fused solution that makes 75 ℃ of insulations 25 minutes so that arranged wherein air bubble, standby;
6) preheating drop pill machine, adjust the temperature-controlling system of drop pill machine, make water dropper temperature constant temperature to 78 ℃, the temperature of coolant remains on 8 ℃, the fluid reservoir that fused solution is placed the drop pill machine drip apart from for 6cm, to drip speed be to splash into coolant under 40 droplets/minute the condition, is condensed into ball; Taken out by the drop pill of drop pill machine exit with molding, the coolant on filtering surface is put and is drying to obtain compound bamboo leave flavone dripping pill in the vacuum drying oven.
The weight ratio of step 1) Chinese crude drug raw material is 6 parts of Folium Bambusaes, 4 portions of Herba Mimosae Pudicaes, measures 70% aquiferous ethanol supersound extraction 40min with 6 times at every turn; Step 2) ultrasonic time is 20min in, and sucking filtration is removed activated carbon, obtains filtrate continuation and is concentrated to 1/8 of original volume.Be dissolved in the low amounts of water concentrating paste behind the n-butanol extraction in the step 4), by Diaion HP-20 macroporous adsorptive resins, the blade diameter length ratio of chromatographic column is 1: 10, uses H earlier
2O and 10% aquiferous ethanol eluting are removed water-solubility impurity, carry out gradient elution with 25% aquiferous ethanol, 35% aquiferous ethanol, 55% aquiferous ethanol successively again, all use 70% aquiferous ethanol eluting to remove all dirt at last, the regeneration macroporous adsorbent resin, above elution flow rate is 12mLmin
-1, collect each position eluents of 3 times of column volumes respectively, merge 25% aquiferous ethanol, 35% aquiferous ethanol, each position eluent of 55% aquiferous ethanol.Mixed-matrix is made up of 1: 5 carboxymethyl starch sodium of weight ratio, Macrogol 4000 in the step 5); The weight ratio of extractive of general flavone and mixed-matrix is 1: 3, and fused solution was 70 ℃ of insulations 20 minutes.In the step 6): the water dropper temperature constant temperature to 70 of drop pill machine ℃, the temperature of coolant remains on 6 ℃, the fluid reservoir that fused solution is placed the drop pill machine drip apart from for 5cm, to drip speed be to splash into coolant under 20 droplets/minute the condition, is condensed into ball.Other is with embodiment 1.
Embodiment 3
The weight ratio of step 1) Chinese crude drug raw material is 8 parts of Folium Bambusaes, 2 portions of Herba Mimosae Pudicaes, measures 65% aquiferous ethanol supersound extraction 50min with 9 times at every turn; Step 2) ultrasonic time is 28min in, and sucking filtration is removed activated carbon, obtains filtrate continuation and is concentrated to 1/11 of original volume.Be dissolved in the low amounts of water concentrating paste behind the n-butanol extraction in the step 4), by Diaion HP-20 macroporous adsorptive resins, the blade diameter length ratio of chromatographic column is 1: 13, uses H earlier
2O and 10% aquiferous ethanol eluting are removed water-solubility impurity, carry out gradient elution with 35% aquiferous ethanol, 45% aquiferous ethanol, 55% aquiferous ethanol successively again, all use 70% aquiferous ethanol eluting to remove all dirt at last, the regeneration macroporous adsorbent resin, above elution flow rate is 13mLmin
-1, collect each position eluents of 3 times of column volumes respectively, merge 35% aquiferous ethanol, 45% aquiferous ethanol, each position eluent of 55% aquiferous ethanol.Mixed-matrix is made up of 1: 5 poloxamer of weight ratio, Macrogol 4000 in the step 5); The weight ratio of extractive of general flavone and mixed-matrix is 1: 4, and fused solution was 76 ℃ of insulations 26 minutes.In the step 6): the water dropper temperature constant temperature to 76 of drop pill machine ℃, the temperature of coolant remains on 9 ℃, the fluid reservoir that fused solution is placed the drop pill machine drip apart from for 7cm, to drip speed be to splash into coolant under 30 droplets/minute the condition, is condensed into ball.Other is with embodiment 1.
Embodiment 4
The weight ratio of step 1) Chinese crude drug raw material is 6 parts of Folium Bambusaes, 4 portions of Herba Mimosae Pudicaes, measures 70% aquiferous ethanol supersound extraction 60min with 10 times at every turn; Step 2) ultrasonic time is 30min in, and sucking filtration is removed activated carbon, obtains filtrate continuation and is concentrated to 1/12 of original volume.Be dissolved in the low amounts of water concentrating paste behind the n-butanol extraction in the step 4), by Diaion HP-20 macroporous adsorptive resins, the blade diameter length ratio of chromatographic column is 1: 15, uses H earlier
2O and 10% aquiferous ethanol eluting are removed water-solubility impurity, carry out gradient elution with 40% aquiferous ethanol, 50% aquiferous ethanol, 60% aquiferous ethanol successively again, all use 70% aquiferous ethanol eluting to remove all dirt at last, the regeneration macroporous adsorbent resin, above elution flow rate is 14mLmin
-1, collect each position eluents of 3 times of column volumes respectively, merge 40% aquiferous ethanol, 50% aquiferous ethanol, each position eluent of 60% aquiferous ethanol.Mixed-matrix is made up of 1: 10 poloxamer of weight ratio, Macrogol 4000 in the step 5); The weight ratio of extractive of general flavone and mixed-matrix is 1: 5, and fused solution was 80 ℃ of insulations 30 minutes.In the step 6): the water dropper temperature constant temperature to 76 of drop pill machine ℃, the temperature of coolant remains on 9 ℃, the fluid reservoir that fused solution is placed the drop pill machine drip apart from for 6cm, to drip speed be to splash into coolant under 60 droplets/minute the condition, is condensed into ball.Other is with embodiment 1.
Embodiment 5
The weight ratio of step 1) Chinese crude drug raw material is 7 parts of Folium Bambusaes, 3 portions of Herba Mimosae Pudicaes, measures 70% aquiferous ethanol supersound extraction 55min with 10 times at every turn; Step 2) ultrasonic time is 26min in, and sucking filtration is removed activated carbon, obtains filtrate continuation and is concentrated to 1/10 of original volume.Be dissolved in the low amounts of water concentrating paste behind the n-butanol extraction in the step 4), by Diaion HP-20 macroporous adsorptive resins, the blade diameter length ratio of chromatographic column is 1: 14, uses H earlier
2O and 10% aquiferous ethanol eluting are removed water-solubility impurity, carry out gradient elution with 30% aquiferous ethanol, 40% aquiferous ethanol, 60% aquiferous ethanol successively again, all use 70% aquiferous ethanol eluting to remove all dirt at last, the regeneration macroporous adsorbent resin, above elution flow rate is 12mLmin
-1, collect each position eluents of 3 times of column volumes respectively, merge 30% aquiferous ethanol, 40% aquiferous ethanol, each position eluent of 60% aquiferous ethanol.Mixed-matrix is made up of 1: 10 poloxamer of weight ratio, polyethylene glycol 6000 in the step 5); The weight ratio of extractive of general flavone and mixed-matrix is 1: 4, and fused solution was 72 ℃ of insulations 24 minutes.In the step 6): the water dropper temperature constant temperature to 72 of drop pill machine ℃, the temperature of coolant remains on 7 ℃, the fluid reservoir that fused solution is placed the drop pill machine drip apart from for 6cm, to drip speed be to splash into coolant under 35 droplets/minute the condition, is condensed into ball.Other is with embodiment 1.
Embodiment 6
The weight ratio of step 1) Chinese crude drug raw material is 8 parts of Folium Bambusaes, 2 portions of Herba Mimosae Pudicaes, measures 65% aquiferous ethanol supersound extraction 50min with 9 times at every turn; Step 2) ultrasonic time is 28min in, and sucking filtration is removed activated carbon, obtains filtrate continuation and is concentrated to 1/9 of original volume.Be dissolved in the low amounts of water concentrating paste behind the n-butanol extraction in the step 4), by Diaion HP-20 macroporous adsorptive resins, the blade diameter length ratio of chromatographic column is 1: 11, uses H earlier
2O and 10% aquiferous ethanol eluting are removed water-solubility impurity, carry out gradient elution with 40% aquiferous ethanol, 45% aquiferous ethanol, 60% aquiferous ethanol successively again, all use 70% aquiferous ethanol eluting to remove all dirt at last, the regeneration macroporous adsorbent resin, above elution flow rate is 13mLmin
-1, collect each position eluents of 3 times of column volumes respectively, merge 40% aquiferous ethanol, 45% aquiferous ethanol, each position eluent of 60% aquiferous ethanol.Mixed-matrix is made up of 1: 10 carboxymethyl starch sodium of weight ratio, polyethylene glycol 6000 in the step 5); The weight ratio of extractive of general flavone and mixed-matrix is 1: 3, and fused solution was 75 ℃ of insulations 25 minutes.In the step 6): the water dropper temperature constant temperature to 75 of drop pill machine ℃, the temperature of coolant remains on 8 ℃, the fluid reservoir that fused solution is placed the drop pill machine drip apart from for 5.5cm, to drip speed be to splash into coolant under 50 droplets/minute the condition, is condensed into ball.Other is with embodiment 1.
Described mixed-matrix is by two kinds of matrix group resulting mixtures in Macrogol 4000, polyethylene glycol 6000, carboxymethyl starch sodium, the poloxamer.Wherein carboxymethyl starch sodium and poloxamer are surfactant, they help the dispersion stripping of medicine, the uniformity and the stability that help drop pill, a kind of composition mixed-matrix in therefore preferred wherein a kind of surfactant and Macrogol 4000, the polyethylene glycol 6000.
One, followingly illustrates that by corresponding test how setting up high performance liquid chromatography carries out active constituent content measuring to the compound bamboo leave flavone dripping pill preparation of the present invention preparation.
1, instrument and reagent
Waters 2695 high performance liquid chromatographs (U.S. Waters company); Waters 2996 PAD detectors (U.S. Waters company); The Empower chromatographic work station.Reference substance orientin, Lutonaretin, apigenin-8-C-glucoside, Saponaretin self-control (identifying) by NMR (Nuclear Magnetic Resonance) spectrum, above reference substance is respectively 99.18%, 98.24%, 98.36% and 98.08% by HPLC area normalization method nominal purity; Methanol is chromatographically pure, and water is ultra-pure water, and other reagent are analytical pure, all filters through 0.45 μ m microporous filter membrane.
2, chromatographic condition and system suitability test
Waters XBridge C
18Post (4.6mm * 250mm, 5 μ m); Mobile phase: methanol-0.05% glacial acetic acid (35: 65); Flow velocity 1.0mLmin
-1Detect wavelength 340nm; 25 ℃ of column temperatures; Sensitivity 0.2AUFS.Under above-mentioned chromatographic condition, orientin, Lutonaretin, apigenin-8-C-glucoside, Saponaretin chromatographic peak and adjacent chromatographic peak separating degree are greater than 2.0, and the theoretical tray number average is greater than 6000.
3, the preparation of reference substance solution
It is a certain amount of that precision takes by weighing orientin, Lutonaretin, apigenin-8-C-glucoside, Saponaretin reference substance respectively, mix back methanol ultrasonic dissolution and standardize solution, make the mixed solution of orientin, Lutonaretin, apigenin-8-C-glucoside, Saponaretin, filter through 0.45 μ m microporous filter membrane, filtrate is product solution in contrast.
4, the preparation of need testing solution
The accurate respectively drop pill sample that takes by weighing a certain amount of different embodiment by the inventive method preparation in the rearmounted conical flask of porphyrize, adds 50 ℃ of following ultrasonic dissolutions of 50mL methanol.Put cold after-filtration, be transferred in the 100mL measuring bottle with methanol constant volume to scale, filter through 0.45 μ m filter membrane, filtrate is as need testing solution, and is standby.
5, linear relationship is investigated
Precision is drawn successively and is mixed reference substance solution 2,4,6,8,10 μ L, measures by above-mentioned chromatographic condition.With reference substance quality X (μ g) is abscissa, and peak area Y is that vertical coordinate carries out linear regression, gets the regression equation of 4 kinds of compositions, and correlation coefficient r is 0.9999.
6, precision test
The accurate absorption mixed reference substance solution, repeat sample introduction 5 times by above-mentioned chromatographic condition, each 10 μ L, the peak area of 4 kinds of flavonoid glycosides of record, the RSD of result of calculation orientin, Lutonaretin, apigenin-8-C-glucoside, Saponaretin is respectively 1.85%, 2.25%, 2.58% and 1.98%, shows that precision is good.
7, stability test
Get same need testing solution, respectively at 0,5,10,24,36,48h sample introduction 10 μ L, the record peak area, the RSD of orientin, Lutonaretin, apigenin-8-C-glucoside, Saponaretin is respectively 2.21%, 2.03%, 2.66% and 1.88% as a result, and the result shows that sample solution is stable in 48h.
8, application of sample recovery test
Precision takes by weighing the same a collection of drop pill sample by the inventive method preparation of 5 parts of known content, it is an amount of to add orientin, Lutonaretin, apigenin-8-C-glucoside, Saponaretin reference substance respectively, press the preparation method preparation and the sample introduction 10 μ L of need testing solution, calculate the average average recovery of each reference substance, the average recovery rate of orientin, Lutonaretin, apigenin-8-C-glucoside, Saponaretin is respectively 98.34%, 100.23%, 102.67% and 101.56% as a result, and RSD is respectively 2.08%, 2.39%, 1.68% and 1.74%.
9, assay
The above-mentioned need testing solution 10 μ L sample introductions of accurate respectively absorption, the record peak area, press standard curve and calculate content, the result is 5.3%～8.8% by the content of orientin in the molding drop pill of the inventive method preparation, the content of Lutonaretin is 4.7%～6.2%, the content of apigenin-8-C-glucoside is 2.4%～5.6%, and the content of Saponaretin is 1.3%～5.1%.
Two, the best proportioning test of compound bamboo leave flavone extract and mixed-matrix sees Table 1, table 2, table 3.
Table 1 extractive of general flavone: the test effect of mixed-matrix (1: 2)
| The mixed-matrix proportioning | Content of dispersion (%) | The ball method of double differences different (%) | Dissolve scattered time limit (minute) | The drop pill shape | The drop pill mouldability | Hardness |
| Macrogol 4000-polyethylene glycol 6000 (1: 1) | 33.33 | 5～10 | 5.6～6.4 | Spherical | Better | Harder |
| Macrogol 4000-polyethylene glycol 6000 (5: 1) | 33.33 | 5～10 | 5.2～6.8 | Oblate spheroid | Relatively poor | Softer |
| Macrogol 4000-carboxymethyl starch sodium (5: 1) | 33.33 | 5～10 | 5.0～6.8 | Pyriform | Relatively poor | Softer |
| Macrogol 4000-carboxymethyl starch sodium (10: 1) | 33.33 | 5～10 | 5.2～6.8 | Eggplant shape | Relatively poor | Softer |
| Polyethylene glycol 6000-carboxymethyl starch sodium (5: 1) | 33.33 | 5～10 | 5.8～6.3 | Spherical | Better | Harder |
| Polyethylene glycol 6000-carboxymethyl starch sodium (10: 1) | 33.33 | 5～10 | 5.0～6.8 | Oblate spheroid | Relatively poor | Softer |
| Macrogol 4000-poloxamer (5: 1) | 33.33 | 5～10 | 5.0～6.8 | Pyriform | Relatively poor | Softer |
| Macrogol 4000-poloxamer (10: 1) | 33.33 | 5～10 | 5.1～6.8 | Eggplant shape | Relatively poor | Softer |
| Polyethylene glycol 6000-poloxamer (5: 1) | 33.33 | 5～10 | 5.7～6.4 | Spherical | Better | Harder |
| Polyethylene glycol 6000-poloxamer (10: 1) | 33.33 | 5～10 | 5.0～6.8 | Eggplant shape | Relatively poor | Softer |
Table 2 extractive of general flavone: the test effect of mixed-matrix (1: 3)
| The mixed-matrix proportioning | Content of dispersion (%) | The ball method of double differences different (%) | Dissolve scattered time limit (minute) | The drop pill shape | The drop pill mouldability | Hardness |
| Macrogol 4000-polyethylene glycol 6000 (1: 1) | 25.00 | 5～10 | 5.9～6.3 | Spheroidal | Good | Hardness is good |
| Macrogol 4000-polyethylene glycol 6000 (5: 1) | 25.00 | 5～10 | 5.2～6.6 | Spheroidal | Good | Hardness is good |
| Macrogol 4000-carboxymethyl starch sodium (5: 1) | 25.00 | 5～10 | 5.4～6.4 | Spheroidal | Good | Hardness is good |
| Macrogol 4000-carboxymethyl starch sodium (10: 1) | 25.00 | 5～10 | 5.2～6.8 | Pyriform | Relatively poor | Softer |
| Polyethylene glycol 6000-carboxymethyl starch sodium (5: 1) | 25.00 | 5～10 | 5.8～6.4 | Spheroidal | Good | Hardness is good |
| Polyethylene glycol 6000-carboxymethyl starch sodium (10: 1) | 25.00 | 5～10 | 5.5～6.8 | Spheroidal | Good | Hardness is good |
| Macrogol 4000-poloxamer (5: 1) | 25.00 | 5～10 | 5.1～6.8 | Spheroidal | Good | Hardness is good |
| Macrogol 4000-poloxamer (10: 1) | 25.00 | 5～10 | 5.5～6.8 | Pyriform | Relatively poor | Softer |
| Polyethylene glycol 6000-poloxamer (5: 1) | 25.00 | 5～10 | 5.6～6.5 | Spheroidal | Good | Hardness is good |
| Polyethylene glycol 6000-poloxamer (10: 1) | 25.00 | 5～10 | 5.0～6.6 | Spheroidal | Good | Hardness is good |
Table 3 extractive of general flavone: the test effect of mixed-matrix (1: 5)
| The mixed-matrix proportioning | Content of dispersion (%) | The ball method of double differences different (%) | Dissolve scattered time limit (minute) | The drop pill shape | The drop pill mouldability | Hardness |
| Macrogol 4000-polyethylene glycol 6000 (1: 1) | 16.67 | 5～10 | 5.6～6.6 | Spheroidal | Good | Hardness is good |
| Macrogol 4000-polyethylene glycol 6000 (5: 1) | 16.67 | 5～10 | 5.2～6.8 | Spheroidal | Good | Hardness is good |
| Macrogol 4000-carboxymethyl starch sodium (5: 1) | 16.67 | 5～10 | 5.0～6.9 | Spheroidal | Good | Hardness is good |
| Macrogol 4000-carboxymethyl starch sodium (10: 1) | 16.67 | 5～10 | 5.2～6.7 | Spheroidal | Good | Hardness is good |
| Polyethylene glycol 6000-carboxymethyl starch sodium (5: 1) | 16.67 | 5～10 | 6.0～6.6 | Spheroidal | Good | Hardness is good |
| Polyethylene glycol 6000-carboxymethyl starch sodium (10: 1) | 16.67 | 5～10 | 5.0～6.8 | Spheroidal | Good | Hardness is good |
| Macrogol 4000-poloxamer (5: 1) | 16.67 | 5～10 | 5.0～6.9 | Spheroidal | Good | Hardness is good |
| Macrogol 4000-poloxamer (10: 1) | 16.67 | 5～10 | 5.3～6.8 | Spheroidal | Good | Hardness is good |
| Polyethylene glycol 6000-poloxamer (5: 1) | 16.67 | 5～10 | 5.5～6.4 | Spheroidal | Good | Hardness is good |
| Polyethylene glycol 6000-poloxamer (10: 1) | 16.67 | 5～10 | 5.1～6.8 | Spheroidal | Good | Hardness is good |
By table 1～3 as can be seen, when the ratio of extractive of general flavone and mixed-matrix is 1: 2,, make the fused solution denseness bigger because the proportion of extractive of general flavone extract is bigger, should not drip and make ball, the roundness of its drop pill, forming degree and hardness are all undesirable; When the ratio of extractive of general flavone and mixed-matrix was 1: 3 and 1: 5, every index was all more satisfactory in the table.But consider that drop pill should possess " triple effect ", " three is little ", the characteristics of " three just ", in order to guarantee that dose is little and curative effect is obvious, supplementary product consumption is unsuitable excessive when proportioning, therefore although extractive of general flavone and substrate ratio are that 1: 3 and 1: 5 o'clock general effect are all better, extractive of general flavone and substrate composition should be preferred 1: 3.
When carrying out proportioning between the different molecular weight polyethylene glycol, with Macrogol 4000 and polyethylene glycol 6000 ratio be 1: 1 be best proportioning; The mixing match that carries out between the different substrates, with Polyethylene Glycol and surfactant ratio be 5: 1 be best proportioning.
The different system conditions of dripping compare the influence of dripping the system effect: under extractive of general flavone and the fixed condition of mixed-matrix configuration proportion, by adopting the different system conditions of dripping (to comprise the fused solution temperature, the fused solution temperature retention time, the water dropper temperature, the temperature of coolant, drip speed, drip distance) system of dripping, comprehensive observing drips the color and luster of the drop pill of the type of making, forming degree, roundness, the molten diffusing time, factors such as hardness, a system condition that optimizes drop pill is 80 ℃ of fused solution temperature, fused solution temperature retention time 20min, 70 ℃ of water dropper temperature, 8～10 ℃ of the temperature of coolant, drip 30～40 droplets/minute of speed, drip apart from being 5cm, described coolant is a liquid paraffin, soybean oil, a kind of in the methyl-monosilane.By investigating the factors such as shape, mouldability, roundness and surface flatness with drop pill after the above-mentioned different coolant cools, preferable methyl silane or liquid paraffin are as coolant.
Claims (9)
1. the preparation method of compound bamboo leave flavone dripping pill is characterized in that comprising following processing step:
1) gets 6～8 parts of Folium Bambusaes and 2～4 portions of Herba Mimosae Pudicaes as medicinal raw material, be ground into coarse powder after the mixing, cross 20～60 mesh sieves, medicinal material coarse powder is measured 50～70% aquiferous ethanol supersound extraction 2～3 times with 6～10 times at 50 ℃ down at every turn, each 30～60min, sucking filtration, merging filtrate;
2) filtrate is concentrated into 1/3～1/5 of original volume at 50 ℃ of following vacuum films of bath temperature, obtain concentrated solution, with concentrated solution powdered active carbon ultrasonic 20～30min under 50 ℃, the consumption of powdered active carbon is a medicinal raw material dry weight 1～2%, remove activated carbon, filtrate continuation is concentrated to 1/8～1/12 of original volume at vacuum film below 50 ℃, obtains concentrated solution once more;
3) with step 2) in the concentrated solution that obtains once more with n-butanol extraction 4 times, preceding 2 each consumptions are 1～1.5 times of amount of concentrated solution volume, 1/2～2/3 times of amount that 2 the each consumptions in back are the concentrated solution volume, combining extraction liquid becomes paste at vacuum concentration below 50 ℃;
4) be dissolved in the low amounts of water concentrating paste behind the n-butanol extraction, by macroporous adsorptive resins, the blade diameter length ratio of chromatographic column is 1: 10～15, uses H earlier
2O and 10% aquiferous ethanol eluting are removed water-solubility impurity, carry out gradient elution with 15～65% aquiferous ethanol more than three kinds or three kinds successively again, all use 70% aquiferous ethanol eluting to remove all dirt at last, the regeneration macroporous adsorbent resin, above elution flow rate is 10～15mLmin
-1Collect each position eluent of 3 times of column volumes respectively, merge each position eluent of 20～60% aquiferous ethanol, it is that 1.2～1.3 thick paste or vacuum drying become dry powder that the eluent that merges is become relative density at vacuum concentration below 50 ℃, promptly gets the compound bamboo leave flavone extract;
5) mixed-matrix is by two kinds of matrix group resulting mixtures in Macrogol 4000, polyethylene glycol 6000, carboxymethyl starch sodium, the poloxamer, and two kinds of substrate are according to the fusion of 1: 1～1: 10 mixed post-heating of weight ratio; The compound bamboo leave flavone extract that makes in the step 4) is pulverized the back cross 200 mesh sieves, add in the fused mixed-matrix and stir, the weight ratio of extractive of general flavone and mixed-matrix is 1: 3～1: 5, the fused solution that makes 70～80 ℃ of insulations 20～30 minutes so that arranged wherein air bubble, standby;
6) place the drop pill machine to make drop pill the fused solution that makes in the step 5), be drying to obtain compound bamboo leave flavone dripping pill.
2. the preparation method of compound bamboo leave flavone dripping pill as claimed in claim 1, it is characterized in that in the step 1): the weight ratio of medicinal raw material is 7～8 parts of Folium Bambusaes, 3～2 portions of Herba Mimosae Pudicaes, measure 60～70% aquiferous ethanol supersound extraction, each 40～55min with 7～8 times at every turn.
3. the preparation method of compound bamboo leave flavone dripping pill as claimed in claim 1 is characterized in that step 2) in: ultrasonic time is 25～28min, and sucking filtration is removed activated carbon, obtains filtrate continuation and is concentrated to 1/9～1/10 of original volume.
4. the preparation method of compound bamboo leave flavone dripping pill as claimed in claim 1, it is characterized in that in the step 4): the blade diameter length ratio of chromatographic column is 1: 10～12, uses H earlier
2O and 10% aquiferous ethanol eluting are removed water-solubility impurity, carry out gradient elution with 20% aquiferous ethanol, 40% aquiferous ethanol, 60% aquiferous ethanol successively again, all use 70% aquiferous ethanol eluting to remove all dirt at last, the regeneration macroporous adsorbent resin, above elution flow rate is 12～14mLmin
-1, collect each position eluents of 3 times of column volumes respectively, merge each position eluent of 20～60% aquiferous ethanol.
5. the preparation method of compound bamboo leave flavone dripping pill as claimed in claim 1, it is characterized in that in the step 5): mixed-matrix is a kind of and Macrogol 4000 in carboxymethyl starch sodium, the poloxamer, a kind of composition in the polyethylene glycol 6000, the weight ratio of two kinds of substrate 1: 3～1: 8.
6. the preparation method of compound bamboo leave flavone dripping pill as claimed in claim 1, it is characterized in that in the step 5): the weight ratio of extractive of general flavone and mixed-matrix is 1: 3～1: 4, fused solution was 72～75 ℃ of insulations 22～25 minutes.
7. the preparation method of compound bamboo leave flavone dripping pill as claimed in claim 1, it is characterized in that in the step 6): the water dropper temperature constant temperature to 70 of drop pill machine～80 ℃, the temperature of coolant remains on 6～10 ℃, the fluid reservoir that fused solution is placed the drop pill machine drip apart from be 5～7cm, to drip speed be to splash into coolant under 20～60 droplets/minute the condition, is condensed into ball; Taken out by the drop pill of drop pill machine exit with molding, the coolant on filtering surface is put and is drying to obtain compound bamboo leave flavone dripping pill in the vacuum drying oven.
8. the preparation method of compound bamboo leave flavone dripping pill as claimed in claim 7, it is characterized in that in the step 6): the water dropper temperature constant temperature to 75 of drop pill machine～78 ℃, the temperature of coolant remains on 7～8 ℃, and dripping distance is that 5.5～6cm, a speed are 30～50 droplets/minute.
9. the preparation method of compound bamboo leave flavone dripping pill as claimed in claim 7 is characterized in that in the step 6): described coolant is a kind of in liquid paraffin, soybean oil, the methyl-monosilane.
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| CN102285976A (en) * | 2011-09-27 | 2011-12-21 | 天津市尖峰天然产物研究开发有限公司 | Method for extracting isoorientin from bamboo leaf flavones |
| CN103719840A (en) * | 2013-11-22 | 2014-04-16 | 镇江市丹徒区南山溪园茶叶专业合作社 | Processing technology of bamboo leaf flavonoid chewable tablets |
| CN109700822B (en) * | 2019-03-13 | 2021-05-07 | 中央民族大学 | Pharmaceutical composition for treating myocardial anoxia reoxygenation injury and preparation method and application thereof |
| CN110101677A (en) * | 2019-05-24 | 2019-08-09 | 蚌埠医学院 | A kind of bamboo extractive chewable tablets and preparation method thereof |
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| CN1228968A (en) * | 1998-03-17 | 1999-09-22 | 浙江农业大学 | Production method for extracting flavonoid compound extract or powder from bamboo leaf |
| CN1596907A (en) * | 2003-09-17 | 2005-03-23 | 昆明老拨云堂药业有限公司 | Use of bamboo leaf flavone in preparation of medicine or health-care food for preventing or treating thrombus disease or blood deficiency disease |
| CN101474240A (en) * | 2009-01-22 | 2009-07-08 | 浙江林学院 | Method for extracting total flavone from sensitive plant |
| CN101508711A (en) * | 2009-03-26 | 2009-08-19 | 浙江林学院 | Method for separating and purifying flavonoid glycoside monomer from sensitive plant |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1228968A (en) * | 1998-03-17 | 1999-09-22 | 浙江农业大学 | Production method for extracting flavonoid compound extract or powder from bamboo leaf |
| CN1596907A (en) * | 2003-09-17 | 2005-03-23 | 昆明老拨云堂药业有限公司 | Use of bamboo leaf flavone in preparation of medicine or health-care food for preventing or treating thrombus disease or blood deficiency disease |
| CN101474240A (en) * | 2009-01-22 | 2009-07-08 | 浙江林学院 | Method for extracting total flavone from sensitive plant |
| CN101508711A (en) * | 2009-03-26 | 2009-08-19 | 浙江林学院 | Method for separating and purifying flavonoid glycoside monomer from sensitive plant |
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