CN101708240B - Heard-brain benefiting dropping pills and method for preparing same - Google Patents
Heard-brain benefiting dropping pills and method for preparing same Download PDFInfo
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Abstract
本发明涉及一种中药制剂，具体是一种治疗心脑血管疾病的中药益心脑滴丸及其制备方法。解决利用天然植物类药物治疗心脑血管疾病的问题。其特征是由下列原料药物按重量比组成：黄芪13-17份、三七5-7份、红花8-10份、栀子8-10份、冰片1-1.5份。本发明所涉及的益心脑滴丸，采用水溶性聚乙二醇固体分散技术，将药物的有效成分以分子、胶体、无定形或超细状态分散于水溶性载体中，提高药物的分散度，减小药物粒度，使比表面积增加，而载体又为水溶性物质，从而改善了药物的溶解性能，加快溶出速度，提高生物利用度，提高了临床疗效，达到速效目的，适用于心脑血管疾病的治疗。The invention relates to a traditional Chinese medicine preparation, in particular to a traditional Chinese medicine Yixinnao dripping pill for treating cardiovascular and cerebrovascular diseases and a preparation method thereof. To solve the problem of using natural plant drugs to treat cardiovascular and cerebrovascular diseases. It is characterized in that it is composed of the following raw materials according to weight ratio: 13-17 parts of astragalus, 5-7 parts of notoginseng, 8-10 parts of safflower, 8-10 parts of gardenia and 1-1.5 parts of borneol. The Yixinnao dripping pills involved in the present invention adopt the water-soluble polyethylene glycol solid dispersion technology to disperse the active ingredients of the medicine in the water-soluble carrier in the form of molecules, colloids, amorphous or ultrafine state, so as to improve the dispersion degree of the medicine , reduce the particle size of the drug, increase the specific surface area, and the carrier is a water-soluble substance, thereby improving the solubility of the drug, accelerating the dissolution rate, improving the bioavailability, improving the clinical efficacy, and achieving the purpose of quick effect. It is suitable for cardiovascular and cerebrovascular disease treatment.
Description
Technical field
The present invention relates to a kind of Chinese medicine preparation, specifically is a kind of Chinese medicine Heard-brain benefiting dropping pills for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof.
Background technology
Cardiovascular and cerebrovascular disease is a kind of major disease of serious harm human body health, and it causes mortality rate and occupy second always, has the characteristics of high prevalence, high disability rate, high mortality.In recent years, the medicine that is used to prevent and treat cardiovascular and cerebrovascular disease is all being obtained remarkable progress aspect Application and Development and the clinical treatment, but clinical practice is mainly based on chemical medicine, and has all occurred side effect in various degree such as gastrointestinal tract and hepatorenal damage in clinical practice.Along with the rise of people's back to nature upsurge, the medicine that excavates and develop efficient prevention of new low toxicity and treatment cardiovascular and cerebrovascular disease from natural plants and Chinese medicine becomes the research focus.
Summary of the invention
The present invention provides a kind of Chinese medicine Heard-brain benefiting dropping pills and preparation method thereof in order to solve the problem of utilizing natural plant kind Drug therapy cardiovascular and cerebrovascular disease.
The present invention is realized by following technical scheme, a kind of Chinese medicine Heard-brain benefiting dropping pills is made up of the following raw materials according medicine: Radix Astragali 13-17 part, Radix Notoginseng 5-7 part, Flos Carthami 8-10 part, Fructus Gardeniae 8-10 part, Borneolum Syntheticum 1-1.5 part, above material medicine can be mixed and made into common pill.
This medicine possesses the treatment cardiovascular and cerebrovascular disease, has the effect of benefiting QI for activating blood circulation, disperse blood stasis and dredge collateral.Cure mainly apoplexy apoplex involving the channels and collaterals, hemiplegia, numb limbs and tense tendons, thoracic obstruction cardio palmus due to blood stagnancy due to deficiency of QI, the venation block.Reuse Radix Astragali in the side for monarch, go into spleen lung two warps, qi-supplementing, blood-engendering makes gas prosperous and to promote blood capable, but and blood stasis dispelling and just not hindering; Radix Notoginseng, Flos Carthami are longer than promoting blood circulation to restore menstrual flow, and stasis-dispelling and pain-killing, two medicines altogether principal drug assistance are set upright and do not held back heresy, and blood stasis dispelling and just not hindering is ministerial drug altogether; Stagnation of QI and blood, strongly fragrant and heat-transformation so use the Fructus Gardeniae clearing away heat-fire, removes the heat of Liver Channel, is adjuvant drug; The Borneolum Syntheticum abnormal smells from the patient is hot fragrant, and its " fragrance is walked to scurry, and priming is up ", blood circulation promoting and dispersing pathogen accumulation, reducing swelling and alleviating pain is messenger drug.All medicines share, and then gas is prosperous and blood is capable, stagnation resolvation and beniol, and QI and blood is ruled together, the heart and brain ruton, all diseases can be removed.
The Radix Astragali is the dry root of the leguminous plant Radix Astagali or the film folder Radix Astragali, it is conventional Chinese medicine simply, effect with invigorating QI to consolidate the body surface resistance, diuresis poison holding, evacuation of pus, expelling pus and promoting granulation, modern pharmacology studies show that it has coronary artery dilator, strengthens anti-anoxia ability, prevents lipid peroxidation, improves effects such as cardiac function.
Radix Notoginseng is the dry root of panax araliaceae plant, is rare Chinese medicine simply, has the effect of dissipating blood stasis hemostasis, subduing swelling and relieving pain.Pharmaceutical research shows, its main active Radix Notoginseng total arasaponins have resist myocardial ischemia, antithrombotic, arrhythmia, blood pressure lowering, accent blood fat, and improve effects such as cerebral circulation.
Flos Carthami is the dry tubular flower of feverfew Flos Carthami, modern pharmacology proves, main effects material base in the Flos Carthami is a Carthamus yellow, multiple pharmacological effect such as it has coronary artery dilator, improve blood supply of cardiac muscle, anticoagulant, inhibition thrombosis, antioxidation are used extremely extensive in the blood circulation promoting and blood stasis dispelling prescription.
Fructus Gardeniae derives from the dry mature fruit of Maguireothamnus speciosus Fructus Gardeniae, and its bitter in the mouth cold in nature has the effect of clearing away heat-fire, removing pathogenic heat from blood and toxic substance from the body, and the pharmacology proves that its extract has effects such as blood pressure lowering, antithrombotic formation and microcirculation improvement.
The Chinese medicine Borneolum Syntheticum is the processed goods (being called " borneol ") of Dipterocarpaceae aiphyllium Borneolum Syntheticum resin, or the extract of feverfew (being called " Blumeae preparatum Tabellae "), or is the be processed into product (be called BORNEOLUM SYNTHETICUM) of raw material through chemosynthesis with Camphora, Oleum Terebinthinae.Modern pharmacology proves, Borneolum Syntheticum energy coronary artery dilator, and coronary blood flow increasing also can promote that some drugs sees through blood brain barrier.Therefore, Borneolum Syntheticum is widely used in the control of the heart, cerebrovascular disease.
In sum, beneficial heart and brain are reasonable recipe not only, and year clinical practice checking surplus ten, and this side is for cardiovascular and cerebrovascular disease determined curative effects such as atherosclerosis, cerebral infarction, coronary heart disease and angina pectoriss.At present, still with simple form medication such as decoction, powder, its dose is big clinically for this side, and stores, carries inconvenience, the needs of the incompatibility modern life.In recent years, along with science and technology development and growth in the living standard, press for and seek a kind of bioavailability height, fast release, dose is little and the novel form of taking convenience to meet clinical needs, to alleviate patient's misery.This invention is studied the preparation technology of Traditional Chinese Medicine Dropping Pill, and this compound recipe is developed as drop pill.In addition, for the extraction process science that guarantees this side, rationally, and help industrialized great production, this invention adopts orthogonal experimental design method, determines the optimum extraction process of this compound recipe to have wide clinical meaning and market prospect with many index comprehensives scorings.
A kind of Chinese medicine Heard-brain benefiting dropping pills is that the best group by the following raw materials according medicine becomes: 15 parts of the Radixs Astragali, 6 parts of Radix Notoginseng, 9 parts on Flos Carthami, 9 parts of Fructus Gardeniaes, 0.5 part of Borneolum Syntheticum.
Preparation method is, (a) extract preparation: the Radix Astragali, Radix Notoginseng, Fructus Gardeniae, Flos Carthami powder are broken into coarse powder, 50% alcohol dipping 24h, 12 times of quality are carried out percolation, collect the liquid of filtering, and the liquid concentrating under reduced pressure of filtering reclaims ethanol, be concentrated into the thick paste of relative density 1.30～1.32 (60～70 ℃), to concentrate the gained thick paste and adopt drying under reduced pressure, cross 100 mesh sieves, get the A product;
(b) clathrate preparation: take by weighing beta-schardinger dextrin-(β-CD) by Borneolum Syntheticum beta-schardinger dextrin-mass ratio 1: 6-10, beta-schardinger dextrin-adds distilled water and makes β-CD saturated solution, at 40 ℃ of alcoholic solution that drip Borneolum Syntheticum down, stir 1-2h, put cold preservation 20-30h in the refrigerator, filter, with the distilled water flush away part β-CD of enclose not, 40 ℃ of dry 24h down pulverize, cross 100 mesh sieves, get the B product;
(c) drop pill preparation: A product and B product mix homogeneously are got the C product; Get substrate PEG4000: PEG6000 presses 2-1: the mass ratio of 1-2 is at 75 ℃ of following heating and meltings; According to the C product: the mass ratio of mixed-matrix=1: 2-3 joins the C product in the molten matrix, stirs, under 75 ℃, be incubated the D product; At last the D product are dripped and make ball.
The beneficial effect of the pill medicine that obtains according to this such scheme:
Heard-brain benefiting dropping pills involved in the present invention, study through modern pharmacology, these materials such as dextro Borneolum Syntheticum in Carthamus yellow in Radix Astragali total saponins in the Radix Astragali, the Radix Notoginseng in Radix Notoginseng total arasaponins, the Flos Carthami, the extract in the Fructus Gardeniae, the Borneolum Syntheticum, effective coronary artery dilator, reduce vascular resistance, increase coronary blood supply; Promote fibrin degradation, improve the body fibrinolytic; Improve erythrocyte deformability, reduce erythrocyte fragmentation, reduce blood viscosity, improve hemorheology; Anticoagulant prolongs thrombus formation time, prolongs thrombin time; Reverse ventricular hypertrophy; Remove free radical, improve myocardial ischemic preconditioning, protecting myocardial cell, this has proved that Heard-brain benefiting dropping pills has positive prevention and therapeutical effect to the generation development of cardiovascular and cerebrovascular disease.
Heard-brain benefiting dropping pills involved in the present invention adopts the water-soluble polyethylene glycol solid dispersion technology, and the effective ingredient of medicine is scattered in the water-solubility carrier with molecule, colloid, amorphous or ultra-fine state, improve the dispersion of medicine, reduce drug particle size, specific surface area is increased, and carrier is a water-soluble substances, thereby improved the solubility property of medicine, accelerate dissolution rate, improve bioavailability, improved clinical efficacy, reach quick-acting purposes, be applicable to the treatment of cardiovascular and cerebrovascular disease.
Heard-brain benefiting dropping pills involved in the present invention can be used for oral or sublingual administration, can make that effective ingredient fully contacts with mucomembranous surface in the medicine, absorbs by mucomembranous epithelial cell, directly enters blood circulation.Sublingual administration can directly enter blood circulation without gastrointestinal tract and liver, effectively avoids first pass effect, characteristics such as having the bioavailability height, take medicine conveniently, side effect is little.
Example surplus the type heart diseases 150 such as clinical treatment coronary atherosclerosis, angina pectoris cures 120, effective percentage 80%.Sensation of oppression over the chest with shortness of breath patient with sympotoms 95 examples are cured 50 examples, 34 examples that take a turn for the better, and effective percentage reaches 90%.Model case
1 patient neat certain, man, 76 years old.Suffer from surplus coronary atherosclerosis heart disease, the angina pectoris ten year, occur pale complexion at present, lethargy, soreness of waist and knee, uncomfortable in chest, anterior pectorial region squeezing sense, the thorough left side of the pain shoulder back of the body, the body of the tongue purple is dim, deep and hesitant pulse and lack, electrocardiogram is pointed out: STv
1-v
6Decline 0.3mv, Tv
1-v
6Be low flat, two-way, be inverted.Through taking Heard-brain benefiting dropping pills 5 months, have rosy cheeks, in high spirits, chest pain is not being shown effect, other all diseases, mistake also fades.The check electrocardiogram shows that ST returns to baseline values.
2 patients bent certain, man, 71 years old.Sensation of oppression over the chest with shortness of breath, pareordia dull pain discomfort was had a surplus in 1 year, how to show effect under angry, tired situation.Because of overworking, pained outbreak is frequent recently, and cold extremities due to sweating, and thoracic obstruction longer duration are with the xerostomia anorexia.Stringy and thready pulse, taking the pulse heavily is unable, thin lingual fur.Modulate half a year through Heard-brain benefiting dropping pills, angina pectoris is outbreak substantially, and above-mentioned symptom all has improvement.This patient is still taking Heard-brain benefiting dropping pills, as a means of consolidation at present.
3 patient Hus, the woman, 56 years old, the patient was diagnosed as viral myocarditis from August, 2007, protracted course of disease still behind the hospitalization.Electrocardio diagram prompting during prescription on individual diagnosis: ST is disconnected to force down myocardial ischemia; Ventricular premature contraction takes place frequently.With pareordia dull pain discomfort, sensation of oppression over the chest with shortness of breath is slept and rather do not wait disease, deep and hesitant pulse night.Through Heard-brain benefiting dropping pills modulation 20 days, self-induction sx.After continue to take medicine and have a surplus March, the close pain of patient's chest disappears, premature beat disappears, all diseases alleviate.Advise it to adhere to taking medicine four months, to consolidate curative effect.Examine in April, 2008 once more, the electrocardiogram no abnormality seen, and all diseases disappear.
4 patient Zhangs, the man, 50 years old, the patient was because of serious stupor, and gatism was in hospital in July, 2006.Through the brain CT examination, be diagnosed as patients with multiple lacunar infarct, the state of an illness is basicly stable behind the hospitalization.Patient's bradykinesia when examining, one's ears rang and spots danced before one's eyes, and it is amesiality to loll, and the left side upper and lower extremities feels like jelly, the left side dizziness headache, deep and hesitant pulse has hypertension history.Have a surplus April through the Heard-brain benefiting dropping pills treatment, conscious brains is salubrious, and spirit takes a turn for the better, and advises it to hold on and takes medicine five or six months, and go to a doctor in February, 2008 once more, and patient's readme left hand can be held light thing, and headache alleviates, and it is placed in the middle to loll, and is in a cheerful frame of mind.
5 patient Cai, the woman, 74 years old, patient's angina pectoris that often shows effect, uncomfortable in chest and twinge, pain very as the strand shape, the both sides of the chest distension, sweating is frequent, red tip of the tongue, there is ecchymosis on the limit, pulse condition stringy and rapid pulse, electrocardiogram prompting: ST
II, III, avfMove down 0.2mv, the T ripple is inverted.Have a surplus March through taking Heard-brain benefiting dropping pills, breast angor is flat, and night sweat is few, other all diseases, and the mistake that also fades holds on again and took Heard-brain benefiting dropping pills four months, and the check electrocardiogram shows that ST recovers baseline values, and it is normal that the T ripple recovers.Advise it to continue to take Heard-brain benefiting dropping pills, to consolidate curative effect.
6 patients gold certain, the woman, 68 years old, before 3 days, the prominent sense of patient was dizzy, lower limb is soft, and two lower limb walkings are unfavorable, go to see a doctor immediately, and through CT examination, brain is found multiple new and old cerebral infarction, through surplus ten days defeated MAILUONING, be aided with Heard-brain benefiting dropping pills treatment 2 months, the dizzy disappearance, lower limb exercise freely, lower limb is not soft.Now still in taking the Heard-brain benefiting dropping pills treatment, to consolidate curative effect.
7 certain suffer to open persons, the woman, 70 years old, the patient was because of uncomfortable in chest, angina pectoris sometimes, precordialgia comes to go to a doctor sometimes, on inspection, 92 times/min of heart rate, electrocardiogram prompting: STv
1-v
6Raise 0.3mv, the high point of T.Through taking Heard-brain benefiting dropping pills one month, above-mentioned symptom all take a favorable turn.Advise it to hold on and take medicine three or four months, go to a doctor in March, 2008 once more, and above-mentioned symptom disappears substantially, and the check electrocardiogram shows that ST recovers baseline values, and it is normal that the T ripple recovers.Advise it to continue to take Heard-brain benefiting dropping pills, as a means of consolidation.
8 patient Luos, the man, 65 years old, the patient was because of housework fatigue recently, and mood is displeased, and it is dizzy to happen suddenly, and falls down, and left half body limb activity is ineffective, hospitalization immediately, the electrocardiogram prompting: the ST section moves down, and the T ripple is inverted, complete right bundle branch block.Then leave hospital through a treatment in month, still can not autonomic activities, dizzy happening occasionally, weak breathing hard, it is not peaceful to sleep night, come to go to a doctor in May, 2007, through taking two first quarter moons of Heard-brain benefiting dropping pills, feel that now numb limbs and tense tendons, pain alleviate to some extent, dizziness is breathed hard and is no longer taken place, advise it to continue to take Heard-brain benefiting dropping pills, consolidate curative effect.
9 patient Wang, the woman, 52 years old, feel oppressed because of feeling left anterior pectorial region recently, shortness of breath and palpitation, lethargy, fatigue angina pectoris attacks then slightly, soreness of waist and knee, the xerostomia anorexia, stringy and thready pulse, taking the pulse heavily is unable, thin lingual fur.Blood pressure 140/80mmHg (taking depressor), above-mentioned symptom still exists during prescription on individual diagnosis, through taking Heard-brain benefiting dropping pills modulation two months, the further consultation of coming, conscious spiritual amelioration, the food of receiving increases, advise to continue taking Heard-brain benefiting dropping pills in the time of four months, above-mentioned symptom is all to improve blood pressure stabilization, and recovered routine work and advised to continue to take Heard-brain benefiting dropping pills, as a means of consolidation.
The specific embodiment
The prescription of embodiment 1, Chinese medicine Heard-brain benefiting dropping pills: Radix Astragali 15g, Radix Notoginseng 6g, Flos Carthami 9g, Fructus Gardeniae 9g, Borneolum Syntheticum 0.5g water solublity solid state substrate of the present invention are polyethylene glycol 6000 (PEG-6000) and Macrogol 4000 (PEG-4000).
Preparation method of the present invention is:
[extract preparation]
A, the Radix Astragali, Radix Notoginseng, Fructus Gardeniae, Flos Carthami powder are broken into coarse powder, earlier with 50% alcohol dipping 24h, 12 times of quality of reuse, 50% ethanol liquid carries out percolation, collects the liquid of filtering with the percolation speed of 5ml/min, and the liquid of filtering in condition is: 60～70 ℃,-0.08MPa concentrating under reduced pressure reclaims ethanol, be concentrated into the thick paste of relative density 1.30～1.32 (60～70 ℃), will concentrate the gained thick paste at 60～70 ℃ ,-0.08Mpa adopts drying under reduced pressure 8h down, cross 100 mesh sieves, get the A product;
[clathrate preparation]
B, take by weighing a certain amount of beta-schardinger dextrin-(β-CD) at 1: 8 by Borneolum Syntheticum beta-schardinger dextrin-mass ratio, add distilled water and make β-CD saturated solution (1 :≤10 mass ratioes), at 40 ℃ of alcoholic solution (1 part of Borneolum Syntheticums: 2 parts of mass ratio configurations of dehydrated alcohol), stir 1.5h, put cold preservation 24h in the refrigerator that slowly drip Borneolum Syntheticum down, filter, with a small amount of distilled water flush away part β-CD of enclose not, 40 ℃ of dry 24h down pulverize, cross 100 mesh sieves, get the B product
[drop pill preparation]
C, A product and B product are even by the prescription mixed gets the C product;
D, by substrate PEG4000: PEG6000=1: 2 mass ratioes are at 75 ℃ of following heating and meltings, and according to C product: the mass ratio of substrate=1: 2 joins C product in the molten matrix, stir, 75 ℃ down insulation deposit, get the D product;
E, the D product are inserted in the drop pill machine liquid storing cup,, drip apart from be 10cm 75 ℃ of insulations,, drip speed and splash in the condensing agent dimethicone under the 30d/min condition, cryogenic temperature is 10 ℃, droplet makes ball, wipes condensing agent with paper scrap, promptly gets 40mg/ ball drop pill finished product.
Heard-brain benefiting dropping pills is used for the treatment of cardiovascular and cerebrovascular disease, has the effect of benefiting QI for activating blood circulation, disperse blood stasis and dredge collateral, is particularly suitable for middle-aged and elderly people and takes, oral a 1～1.5g, three times on the one.
The present invention adopts orthogonal experimental design method, determines the optimum extraction process of this compound recipe with the scoring of many index comprehensives, guarantees this side's extraction process science, rationally to be beneficial to industrialized great production.
1. extraction process
1.1 EXPERIMENTAL DESIGN: adopt orthogonal experiment, concentration of alcohol, ethanol consumption, soak time, percolation speed four factors three levels are investigated, utilize each index components content of high effective liquid chromatography for measuring, and this technology is carried out scientific evaluation in conjunction with many index comprehensives point system, the factor level table sees Table 1, and experimental result sees Table 2.
Table 1 factor level table
Take by weighing 9 parts of medicinal material coarse powder in the prescription ratio, carry out percolation, collect the liquid of filtering, be settled to 600ml by orthogonality condition.
Measuring the results are shown in Table 2
Table 2 extraction process orthogonal experiments
1.2 demonstration test is by fixed optimum extraction process condition, i.e. 50% alcohol dipping 24h, and 12 times of quality are carried out percolation, and the percolation flow velocity is 5mlmin
-1, repeated trials 3 times.Demonstration test result and orthogonal experiments are close, and process stabilizing is described, and be rationally feasible.The results are shown in Table 3.
Table 3 demonstration test result
2. clathrate process
2.1 EXPERIMENTAL DESIGN
Adopt L
9(3
4) orthogonal design, investigate the principal element that influences the enclose effect: Borneolum Syntheticum beta-schardinger dextrin-ratio, enclose time, enclose temperature, the factor level table sees Table 4.
Table 4 orthogonal test factor level table
2.2 clathrate preparation
Get a certain amount of beta-schardinger dextrin-(β-CD), add an amount of distilled water and make β-CD saturated solution, under set point of temperature, slowly drip the alcoholic solution of Borneolum Syntheticum, be stirred to the stipulated time, put cold preservation 24h in the refrigerator, filter, with a small amount of distilled water flush away β-CD of enclose not partly, dry 24h under 40 ℃, promptly.
Table 5 orthogonal experiments
2.3 by fixed best clathrate process condition is that Borneolum Syntheticum β-CD mass ratio is 1: 8, the enclose temperature is 40 ℃, and the enclose time is 1.5h, repeated trials 3 times.Demonstration test result and orthogonal experiments are close, and process stabilizing is described, and be rationally feasible.The results are shown in Table 6.
Table 6 demonstration test result
3. preparation process
1. the mass ratio of substrate (PEG4000 and PEG6000)
Experimental example 1 with drug powder and fusion substrate (PEG4000 and PEG6000=3: 1) mix homogeneously, splash into it in the condensing agent dimethicone of phase mixing not, (medicine and substrate ratio are 1: 2 to fix other conditions; Dripping the system temperature is 75 ℃; Dripping speed is 30d/min), drip and make ball.
Experimental example 2 with drug powder and fusion substrate (PEG4000 and PEG6000=2: 1) mix homogeneously, splash into it in the condensing agent dimethicone of phase mixing not, (medicine and substrate ratio are 1: 2 to fix other conditions; Dripping the system temperature is 75 ℃; Dripping speed is 30d/min), drip and make ball.
Experimental example 3 with drug powder and fusion substrate (PEG4000 and PEG6000=1: 1) mix homogeneously, splash into it in the condensing agent dimethicone of phase mixing not, (medicine and substrate ratio are 1: 2 to fix other conditions; Dripping the system temperature is 75 ℃; Dripping speed is 30d/min), drip and make ball.
Experimental example 4 with drug powder and fusion substrate (PEG4000 and PEG6000=1: 2) mix homogeneously, splash into it in the condensing agent dimethicone of phase mixing not, (medicine and substrate ratio are 1: 2 to fix other conditions; Dripping the system temperature is 75 ℃; Dripping speed is 30d/min), drip and make ball.
Experimental example 5 with drug powder and fusion substrate (PEG4000 and PEG6000=1: 3) mix homogeneously, splash into it in the condensing agent dimethicone of phase mixing not, (medicine and substrate ratio are 1: 2 to fix other conditions; Dripping the system temperature is 75 ℃; Dripping speed is 30d/min), drip and make ball.
Result of the test sees Table 7.
The influence of table 7 substrate comparison drop pill molding
Conclusion: by record in the table as can be known, as PEG4000: PEG6000 is 2: 1-1: in the time of between 2, the amalgamation of medicinal liquid is good, and drop pill is plastic.
The ratio of 2 medicines and substrate
Experimental example 1 is with drug powder and fusion substrate (medicine: substrate=1: 1) mix homogeneously, observe medicine and the blended complexity of substrate and drip the type situation of making, determine the ratio range of medicine and substrate, fix other conditions (PEG4000 and PEG6000=1: 2; Dripping the system temperature is 75 ℃; Dripping speed is 30d/min), drip and make ball.
Experimental example 2 is with drug powder and fusion substrate (medicine: substrate=1: 2) mix homogeneously, observe medicine and the blended complexity of substrate and drip the type situation of making, determine the ratio range of medicine and substrate, fix other conditions (PEG4000 and PEG6000=1: 2; Dripping the system temperature is 75 ℃; Dripping speed is 30d/min), drip and make ball.
Experimental example 3 is with drug powder and fusion substrate (medicine: substrate=1: 3) mix homogeneously, observe medicine and the blended complexity of substrate and drip the type situation of making, determine the ratio range of medicine and substrate, fix other conditions (PEG4000 and PEG6000=1: 2; Dripping the system temperature is 75 ℃; Dripping speed is 30d/min), drip and make ball.
Experimental result sees Table 8.
Table 8 medicine and substrate ratio are to the influence of drop pill molding
By experiment as can be known, the drug ratios height, drop pill easily trails, and roundness is bad, and medicine and substrate maximum ratio are 1: 2.
3 moulding processs:
3.1 behind fixing distance, a speed and the coolant temperature, the ratio of the ratio of PEG4000 and PEG6O00, medicine and substrate, three aspects investigations of system feed temperature drop pill moulding process from substrate.The quality examination project of drop pill comprises objective indicator, as the molten diffusing time, the ball method of double differences is different, roundness etc., but only use these indexs, be difficult to reflect the quality of drop pill comprehensively, need be to estimating the index of drop pill presentation quality, as hardness, the equal first-class of color and luster is judged, but this judgement has certain subjectivity again, for reducing its error, with each concrete performance assessment criteria by good to poor, be designated as 1 respectively, 2,3 minutes, with hardness and color and luster this two " subjective index " adds and after, as " presentation quality " of drop pill, with " molten diffusing time ", " the ball method of double differences is different " and " roundness " objective indicator comprehensive grading are estimated the quality of drop pill jointly.
3.2 adopt the test of three factors, three horizontal quadratures, investigate the principal element influence the drop pill molding: PEG4000: PEG 6000 (2: 1,1: 1,1: 2), medicine base ratio (1: 2,1: 3,1: 4), chemical medicine temperature (70 ℃, 75 ℃, 80 ℃), fixing distance is 10cm, dripping speed is 30d/min, and the condensing agent temperature is 10 ℃, obtains 9 groups of different experimental results.See Table 9
Table 9 orthogonal experiments
The result shows: best molding technological condition is PEG4000: PEG6000=1: 2, and medicine: substrate=1: 2, chemical medicine temperature are 75 ℃.
4. drip system technology: investigate the principal element that system is dripped in influence: drip apart from (5cm, 10cm, 15cm), condensing agent temperature (5 ℃, 10 ℃, 15 ℃), drip speed (30d/min, 40d/min, 50d/min), PEG4000 under best molding technological condition: PEG6000=1: 2, medicine: substrate=1: 2, chemical medicine temperature are 75 ℃ and drip the investigation of system technology.Obtain 9 groups of different experimental results.See Table 10.
Table 10 orthogonal experiments
Moulding process in conjunction with drop pill is made technology as can be known with dripping: the optimal formulation process conditions are PEG4000: PEG6000=1: 2, medicine: substrate=1: 2, chemical medicine temperature are 75 ℃, and dripping distance is 10cm, dripping speed is 30d/min, and dimethicone is made ball at 10 ℃ following.
The prescription of embodiment 2, Chinese medicine Heard-brain benefiting dropping pills: Radix Astragali 13g, Radix Notoginseng 7g, Flos Carthami 8g, Fructus Gardeniae 10g, Borneolum Syntheticum 1g water solublity solid state substrate of the present invention are polyethylene glycol 6000 (PEG-6000) and Macrogol 4000 (PEG-4000).
Preparation method of the present invention is:
[extract preparation]
A, the Radix Astragali, Radix Notoginseng, Fructus Gardeniae, Flos Carthami powder are broken into coarse powder, 50% alcohol dipping 24h, 12 times of amounts are carried out percolation, collect the liquid of filtering with the percolation speed of 5ml/min, and the liquid of filtering in condition is: 60 ℃,-0.08MPa concentrating under reduced pressure reclaims ethanol, be concentrated into the thick paste of relative density 1.30～1.32, will concentrate the gained thick paste at 60～70 ℃ ,-0.08Mpa adopts drying under reduced pressure 8h down, cross 100 mesh sieves, get the A product;
[clathrate preparation]
B, take by weighing a certain amount of beta-schardinger dextrin-(β-CD) at 1: 8 by Borneolum Syntheticum beta-schardinger dextrin-mass ratio, add distilled water and make β-CD saturated solution, at 40 ℃ of alcoholic solution that slowly drip Borneolum Syntheticum down, stir 1.5h, put cold preservation 24h in the refrigerator, filter, with a small amount of distilled water flush away part β-CD of enclose not, 40 ℃ of dry 24h down pulverize, cross 100 mesh sieves, get the B product
[drop pill preparation]
C, A product and B product are even by the prescription mixed gets the C product;
D, by substrate PEG4000: PEG6000=1: 1 at 75 ℃ of following heating and meltings, and according to C product: the ratio of substrate=1: 2 joins C product in the molten matrix, stir, 75 ℃ down insulation deposit, get the D product;
E, the D product are inserted in the drop pill machine liquid storing cup,, drip apart from be 10cm 75 ℃ of insulations,, drip speed and splash in the condensing agent dimethicone under the 30d/min condition, cryogenic temperature is 10 ℃, droplet makes ball, wipes condensing agent with paper scrap, promptly gets 40mg/ ball drop pill finished product.
The prescription of embodiment 3, Chinese medicine Heard-brain benefiting dropping pills: Radix Astragali 17g, Radix Notoginseng 5g, Flos Carthami 10g, Fructus Gardeniae 8g, Borneolum Syntheticum 1.5g water solublity solid state substrate of the present invention are polyethylene glycol 6000 (PEG-6000) and Macrogol 4000 (PEG-4000).
Preparation method of the present invention is:
[extract preparation]
A, the Radix Astragali, Radix Notoginseng, Fructus Gardeniae, Flos Carthami powder are broken into coarse powder, 50% alcohol dipping 24h, 12 times of amounts are carried out percolation, collect the liquid of filtering with the percolation speed of 5ml/min, and the liquid of filtering in condition is: 70 ℃,-0.08MPa concentrating under reduced pressure reclaims ethanol, be concentrated into the thick paste of relative density 1.30～1.32, will concentrate the gained thick paste at 60～70 ℃ ,-0.08Mpa adopts drying under reduced pressure 8h down, cross 100 mesh sieves, get the A product;
[clathrate preparation]
B, take by weighing a certain amount of beta-schardinger dextrin-(β-CD) at 1: 8 by Borneolum Syntheticum beta-schardinger dextrin-mass ratio, add distilled water and make β-CD saturated solution, at 40 ℃ of alcoholic solution that slowly drip Borneolum Syntheticum down, stir 1.5h, put cold preservation 24h in the refrigerator, filter, with a small amount of distilled water flush away part β-CD of enclose not, 40 ℃ of dry 24h down pulverize, cross 100 mesh sieves, get the B product
[drop pill preparation]
C, A product and B product are even by the prescription mixed gets the C product;
D, by substrate PEG4000: PEG6000=2: 2 at 75 ℃ of following heating and meltings, and according to C product: the ratio of substrate=1: 2.5 joins C product in the molten matrix, stir, 75 ℃ down insulation deposit, get the D product;
E, the D product are inserted in the drop pill machine liquid storing cup,, drip apart from be 10cm 75 ℃ of insulations,, drip speed and splash in the condensing agent dimethicone under the 30d/min condition, cryogenic temperature is 10 ℃, droplet makes ball, wipes condensing agent with paper scrap, promptly gets 40mg/ ball drop pill finished product.
Claims (4)
1. a Chinese medicine Heard-brain benefiting dropping pills is characterized in that being made up of by weight the following raw materials according medicine: Radix Astragali 13-17 part, Radix Notoginseng 5-7 part, Flos Carthami 8-10 part, Fructus Gardeniae 8-10 part, Borneolum Syntheticum 1-1.5 part.
2. Chinese medicine Heard-brain benefiting dropping pills according to claim 1 is characterized in that being made up of the following raw materials according medicine: 15 parts of the Radixs Astragali, 6 parts of Radix Notoginseng, 9 parts on Flos Carthami, 9 parts of Fructus Gardeniaes, 0.5 part of Borneolum Syntheticum.
3. the preparation method of a Chinese medicine Heard-brain benefiting dropping pills is characterized in that may further comprise the steps:
(a) extract preparation: 15 parts of the Radixs Astragali, 6 parts of Radix Notoginseng, 9 parts of Fructus Gardeniaes, Flos Carthami are ground into coarse powder for 9 parts, 50% alcohol dipping 24h, 12 times of quality are carried out percolation, the collection liquid of filtering, the liquid concentrating under reduced pressure of filtering reclaims ethanol, and the survey relative density is 1.30～1.32 thick paste when being concentrated into 60～70 ℃, will concentrate the gained thick paste and adopt drying under reduced pressure, cross 100 mesh sieves, get the A product;
(b) clathrate preparation: get 0.5 part of Borneolum Syntheticum, by Borneolum Syntheticum beta-schardinger dextrin-mass ratio 1: 6-10 takes by weighing beta-schardinger dextrin-, and beta-schardinger dextrin-adds distilled water and makes β-CD saturated solution, at 40 ℃ of alcoholic solution that drip Borneolum Syntheticums down, stir 1-2h, put cold preservation 20-30h in the refrigerator, filter, use the not β-CD of enclose of distilled water flush away part, dry 20-30h under 40 ℃, pulverize, cross 100 mesh sieves, get the B product;
(c) drop pill preparation: A product and B product mix homogeneously are got the C product; Get substrate PEG4000:PEG6000 by the mass ratio of 2-1: 1-2 at 75 ℃ of following heating and meltings; According to the C product: the mass ratio of substrate=1: 2-3 joins the C product in the molten matrix, stirs, under 75 ℃, be incubated the D product; At last the D product are dripped and make ball.
4. as the preparation method of Chinese medicine Heard-brain benefiting dropping pills as described in the claim 3, it is characterized in that may further comprise the steps:
(a) extract preparation: 15 parts of the Radixs Astragali, 6 parts of Radix Notoginseng, 9 parts of Fructus Gardeniaes, Flos Carthami are ground into coarse powder for 9 parts, 50% alcohol dipping 24h, 12 times of quality are carried out percolation, the collection liquid of filtering, the liquid concentrating under reduced pressure of filtering reclaims ethanol, and the survey relative density is 1.30～1.32 thick paste when being concentrated into 60～70 ℃, will concentrate the gained thick paste and adopt drying under reduced pressure, cross 100 mesh sieves, get the A product;
(b) clathrate preparation: get 0.5 part of Borneolum Syntheticum, take by weighing beta-schardinger dextrin-at 1: 8 by Borneolum Syntheticum beta-schardinger dextrin-mass ratio, beta-schardinger dextrin-adds distilled water and makes β-CD saturated solution, at 40 ℃ of alcoholic solution that drip Borneolum Syntheticum down, stir 1.5h, put cold preservation 24h in the refrigerator, filter, use the not β-CD of enclose of distilled water flush away part, dry 24h under 40 ℃, pulverize, cross 100 mesh sieves, get the B product;
(c) drop pill preparation: A product and B product mix homogeneously are got the C product; Get substrate PEG4000:PEG6000 by 1: 2 mass ratio at 75 ℃ of following heating and meltings; According to the C product: the mass ratio of substrate=1: 2 joins the C product in the molten matrix, stirs, under 75 ℃, be incubated the D product; At last the D product are dripped and make ball.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1404847A (en) * | 2001-08-09 | 2003-03-26 | 项钧 | Medicine for treating sequel resulted from cardio-cerebral blood-vessel diseases |
| CN1600318A (en) * | 2003-09-23 | 2005-03-30 | 天津天士力制药股份有限公司 | Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease |
| CN1919238A (en) * | 2005-08-24 | 2007-02-28 | 天津天士力现代中药研究开发有限公司 | Medicine for treating cardiovascular and cerebrovascular disease |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1404847A (en) * | 2001-08-09 | 2003-03-26 | 项钧 | Medicine for treating sequel resulted from cardio-cerebral blood-vessel diseases |
| CN1600318A (en) * | 2003-09-23 | 2005-03-30 | 天津天士力制药股份有限公司 | Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease |
| CN1919238A (en) * | 2005-08-24 | 2007-02-28 | 天津天士力现代中药研究开发有限公司 | Medicine for treating cardiovascular and cerebrovascular disease |
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