CN103127309A - Eight-medicine composition Chinese Eaglewood dropping pill for treating myocardial ischemia, and its preparation method - Google Patents
Eight-medicine composition Chinese Eaglewood dropping pill for treating myocardial ischemia, and its preparation method Download PDFInfo
- Publication number
- CN103127309A CN103127309A CN2013100639896A CN201310063989A CN103127309A CN 103127309 A CN103127309 A CN 103127309A CN 2013100639896 A CN2013100639896 A CN 2013100639896A CN 201310063989 A CN201310063989 A CN 201310063989A CN 103127309 A CN103127309 A CN 103127309A
- Authority
- CN
- China
- Prior art keywords
- extract
- weight portions
- volatile oil
- obtains
- extraction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Landscapes
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a medicinal composition dropping pill for treating myocardial ischemia, and its preparation method. The composition dropping pill is prepared through using 112-169 parts by weight of a primary medicine extract, 21-31 parts by volume of volatile oil, 300-450 parts by weight of polyethylene glycol 4000, 100-150 parts by weight of polyethylene glycol 6000 and 27-40 parts by weight of aerosil. The preparation method comprises the following steps: heating polyethylene glycol 4000 and polyethylene glycol 6000 in a water bath for melting to obtain a matrix, taking the primary medicine extract, adding aerosil to the primary medicine extract, uniformly mixing, adding the mixed primary medicine extract and the volatile oil to the molten matrix, uniformly mixing, carrying out heat insulation at 85DEG C, adding the obtained mixture to cooled dimethicone 100 in a dropwise wise under a speed of 30 droplets/min, condensing in a segment mode which is characterized in that the temperature of the upper portion of a cooling liquid is 20DEG C and the temperature of the lower portion of the cooling liquid is not higher than 5DEG C, and dropping to obtain the pill. The eight-medicine Chinese Eaglewood dropping pill has the characteristics of fast dissolving, fast absorption, fast effectiveness, and high bioavailability.
Description
Technical field
The present invention relates to a kind of medicament composition dropping pills and preparation method thereof, particularly a kind of pharmaceutical composition Bawei Chenxiang drop pill for the treatment of myocardial ischemia and preparation method thereof.
Background technology
The Bawei Chenxiang ball records in the Tibetan medicine ministry standard, standard number: WS
3-BC-0235-95 is pill.Its formula consists of: Lignum Aquilariae Resinatum 100g, Semen Myristicae 100g, Fructus Choerospondiatis 100g, Fructus Chebulae 100g, Olibanum 50g, Radix Aucklandiae 175g, Flos Bombacis Malabarici 75g, Tufa 50g.Bawei Chenxiang ball preparation method is: above eight flavors, be ground into fine powder, and sieve, mixing is used water pill, drying, and get final product.Have the heat of clearing away heart-fire, mind calming is calmed the nerves, the function of having one's ideas straightened out.Be used for calentura and make a psychological attack, unconsciousness and delirium, pareordia pain and cardiotrauma.The Bawei Chenxiang ball records the earliest in the appropriate first Dan Gongbu of space (708-835) the classical literature Four-Volume Medical Code, so far have the clinical practice history of more than 1300, be that the appropriate first Dan Gongbu of space practises medicine and sums up one of 1,100 ancient proved recipes that the folk medicine experience develops in process, curative effect is peculiar." doctor's allusion quotation " record: just take this medicine when heart is wounded by sharp instruments such as arrows.The Bawei Chenxiang ball is the representative drugs that the successive dynasties Tibetan medicine is used for the treatment of myocardial ischemia, traumatic heart disease.The Bawei Chenxiang ball is widely known now, is one of proved recipe commonly used of various places Tibetan medicine hospital.Due to respond well, evident in efficacy through clinical verification, enjoy clinically the patient to favor.
The health of myocardial ischemia serious harm middle-aged and elderly people, in recent years along with growth in the living standard, coronary atherosclerosis presents the trend of rejuvenation, and the performance of myocardial ischemia also appears in the youngster in some 20-30 years.The danger that myocardial infarction and sudden death occur is arranged due to myocardial ischemia, when therefore finding myocardial ischemia, reach early treatment.Bawei Chenxiang ball preparation method is that medical material fine powder mixing is made, the effective ingredient dissolution rate is slow, bioavailability is low, drop pill is to utilize fusion method to prepare a kind of dosage form of solid dispersions technique preparation, fast because of its dissolving, absorb fast, effect is fast, bioavailability is high, be applicable to Chinese medicine emergency case preparation, reach efficient, quick-acting purposes.Bawei Chenxiang ball determined curative effect, market prospect is wide, but present pill production technology backwardness, disintegration time length, mouthfeel and poor compliance, very big curative effect and the popularization that must affect product.
Summary of the invention
For the deficiencies in the prior art, the invention provides a kind of prescription take traditional Tibetan medicine Bawei Chenxiang ball and cross dosage changing form as basic square tube and prepare a kind of pharmaceutical composition Bawei Chenxiang drop pill that is used for the treatment of myocardial ischemia, the present invention also provides the preparation method of this drop pill.
Technical scheme of the present invention is as follows:
A kind of pharmaceutical composition Bawei Chenxiang drop pill for the treatment of myocardial ischemia, made by the supplementary material of following weight portion:
Principal agent extract 112-169 weight portion,
Volatile oil 21-31 parts by volume,
Macrogol 4000 300-450 weight portion,
Polyethylene glycol 6000 100-150 weight portion,
Micropowder silica gel 27-40 weight portion.
The unit of above weight portion and parts by volume is: g/ml or kg/l.
Described principal agent extract and volatile oil make as follows: (1) is got Lignum Aquilariae Resinatum 100 weight portions, Semen Myristicae 100 weight portions, Olibanum 50 weight portions, the Radix Aucklandiae 175 weight portions 4 flavor pulverizing medicinal materials by the crude drug composition and ratio and is crossed the 30-50 mesh sieve, adopt supercritical carbon dioxide extraction method to extract volatile oil, extracting pressure 25-30MPa, extraction temperature 40-50 ℃, extraction time 2.5-3 hour, get volatile oil standby; Medicinal residues extracting in water 2-3 time with extracting after volatile oil adds 6-8 times of water gaging at every turn and extracted 2-3 hour, merging filtrate, and filtration gets aqueous extract A and medicinal residues A ＇; (2) get Fructus Choerospondiatis 100 weight portions, Fructus Chebulae's 100 weight portions, Flos Bombacis Malabarici 75 weight portions, Tufa 50 weight portions totally 4 flavor medical materials by the crude drug composition and ratio, the medicinal residues A ' that obtains with step (1) mixes, alcohol reflux 2-3 time that adds volume fraction 40%-50%, the amount of alcohol that at every turn adds is 8-10 times of total medical material amount, the each extraction 2-3 hour, filter, merging filtrate gets ethanol extract B; (3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.18 ~ 1.25 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), standing 12-24h filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.08 ~ 1.12 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract.
Preferred according to the present invention, a kind of pharmaceutical composition Bawei Chenxiang drop pill for the treatment of myocardial ischemia, made by the supplementary material of following parts by weight: principal agent extract 131-150 weight portion,
Volatile oil 24-28 parts by volume,
Macrogol 4000 350-400 weight portion,
Polyethylene glycol 6000 117-133 weight portion,
Micropowder silica gel 31-36 weight portion.
Further preferred, a kind of pharmaceutical composition Bawei Chenxiang drop pill for the treatment of myocardial ischemia, made by following supplementary material:
Principal agent extract 135g,
Volatile oil 25ml,
Macrogol 4000 360g,
Polyethylene glycol 6000 120g,
Micropowder silica gel 32g.
described principal agent extract and volatile oil make as follows: (1) gets Lignum Aquilariae Resinatum 100g by the crude drug composition and ratio, Semen Myristicae 100g, Olibanum 50g, Radix Aucklandiae 175g4 flavor pulverizing medicinal materials is crossed 40 mesh sieves, adopt supercritical carbon dioxide extraction method to extract volatile oil, extracting pressure 25MPa, 40 ℃ of extraction temperature, extraction time 2.5 hours, get volatile oil standby, with twice of the medicinal residues extracting in water that extracts after volatile oil, adding for the first time 8 times of water gagings extracted 2 hours, adding for the second time 6 times of water gagings extracted 2 hours, merging filtrate, filter, get aqueous extract A and medicinal residues A ＇, (2) get Fructus Choerospondiatis 100g, Fructus Chebulae 100g, Flos Bombacis Malabarici 75g, Tufa 50g totally 4 flavor medical materials by the crude drug composition and ratio, mix with the medicinal residues A ＇ that step (1) obtains, the alcohol reflux 2 times that adds volume fraction 50%, the amount of alcohol that adds for the first time is 10 times of total medical material amount, the amount of alcohol that adds for the second time is 8 times of total medical material amount, the each extraction 2 hours filters, and merging filtrate gets ethanol extract B, (3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.25 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), standing 20h filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.08 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract.
Can add conventional adjuvant in the raw material of pharmaceutical composition Bawei Chenxiang drop pill of the present invention, be prepared into pharmaceutically acceptable any dosage form according to common process.
A kind of preparation method for the treatment of the pharmaceutical composition Bawei Chenxiang drop pill of myocardial ischemia of the present invention comprises the following steps:
(1) get Lignum Aquilariae Resinatum 100 weight portions, Semen Myristicae 100 weight portions, Olibanum 50 weight portions, the Radix Aucklandiae 175 weight portions 4 flavor pulverizing medicinal materials by the crude drug composition and ratio and cross the 30-50 mesh sieve, adopt supercritical carbon dioxide extraction method to extract volatile oil, extracting pressure 25-30MPa, extraction temperature 40-50 ℃, extraction time 2.5-3 hour, get volatile oil standby, with medicinal residues extracting in water 2-3 time that extracts after volatile oil, add 6-8 times of water gaging extracted 2-3 hour at every turn, merging filtrate, filter, get aqueous extract A and medicinal residues A ＇;
(2) get Fructus Choerospondiatis 100 weight portions, Fructus Chebulae's 100 weight portions, Flos Bombacis Malabarici 75 weight portions, Tufa 50 weight portions totally 4 flavor medical materials by the crude drug composition and ratio, mix with the medicinal residues A ＇ that step (1) obtains, alcohol reflux 2-3 time that adds volume fraction 40%-50%, the amount of alcohol that at every turn adds is 8-10 times of total medical material amount, the each extraction 2-3 hour, filter, merging filtrate gets ethanol extract B;
(3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.18 ~ 1.25 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), standing 12-24h filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.08 ~ 1.12 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract;
(4) taking polyethylene glycol 4000 and polyethylene glycol 6000 mix, 80 ℃ of heating in water bath make and melt to get substrate, get the principal agent extract that obtains in step (3), add the micropowder silica gel mix homogeneously, the volatile oil that obtains in the principal agent extract that mixes and step (1) is joined melt in good substrate, mixing, 80 ℃ of-85 ℃ of insulations, splash in cooling dimethicone 100, dripping becomes ball, and get final product.
Preferably, a kind of preparation method for the treatment of the pharmaceutical composition Bawei Chenxiang drop pill of myocardial ischemia of the present invention comprises the following steps:
(1) get Lignum Aquilariae Resinatum 100 weight portions, Semen Myristicae 100 weight portions, Olibanum 50 weight portions, the Radix Aucklandiae 175 weight portions 4 flavor pulverizing medicinal materials by the crude drug composition and ratio and cross 40 mesh sieves, adopt supercritical carbon dioxide extraction method to extract volatile oil, extracting pressure 25MPa, 40 ℃ of extraction temperature, extraction time 2.5 hours, get volatile oil standby, with twice of the medicinal residues extracting in water that extracts after volatile oil, adding for the first time 8 times of water gagings extracted 2 hours, adding for the second time 6 times of water gagings extracted 2 hours, merging filtrate filters, and gets aqueous extract A and medicinal residues A ＇;
(2) get Fructus Choerospondiatis 100 weight portions, Fructus Chebulae's 100 weight portions, Flos Bombacis Malabarici 75 weight portions, Tufa 50 weight portions totally 4 flavor medical materials by the crude drug composition and ratio, mix with the medicinal residues A ＇ that step (1) obtains, the alcohol reflux 2 times that adds volume fraction 50%, the amount of alcohol that adds for the first time is 10 times of total medical material amount, the amount of alcohol that adds for the second time is 8 times of total medical material amount, the each extraction 2 hours filters, and merging filtrate gets ethanol extract B;
(3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.25 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), standing 20h filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.08 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract;
(4) taking polyethylene glycol 4000 and polyethylene glycol 6000,80 ℃ of heating in water bath make and melt to get substrate, get the principal agent extract that obtains in step (3), add the micropowder silica gel mix homogeneously, volatile oil in the principal agent extract that mixes and step (1) is joined melt in good substrate, mixing is 85 ℃ of insulations, the speed of 30 droplets/minute splashes in cooling dimethicone 100, adopt the mode of segmentation condensation, 20 ℃, liquid coolant top, the bottom is not higher than 5 ℃, dripping becomes ball, and get final product.
Preferably, a kind of preparation method for the treatment of the pharmaceutical composition Bawei Chenxiang drop pill of myocardial ischemia of the present invention comprises the following steps:
(1) get Lignum Aquilariae Resinatum 100 weight portions, Semen Myristicae 100 weight portions, Olibanum 50 weight portions, the Radix Aucklandiae 175 weight portions 4 flavor pulverizing medicinal materials by the crude drug composition and ratio and cross 30 sieves, adopt supercritical carbon dioxide extraction method to extract volatile oil, extracting pressure 30MPa, 50 ℃ of extraction temperature, extraction time 3 hours, get volatile oil standby, medicinal residues extracting in water 3 times with extracting after volatile oil adds 8 times of water gagings at every turn and extracted 3 hours, merging filtrate, filter, get aqueous extract A and medicinal residues A ＇;
(2) get Fructus Choerospondiatis 100 weight portions, Fructus Chebulae's 100 weight portions, Flos Bombacis Malabarici 75 weight portions, Tufa 50 weight portions totally 4 flavor medical materials by the crude drug composition and ratio, mix with the medicinal residues A ＇ that step (1) obtains, the alcohol reflux 3 times that adds volume fraction 40%, the amount of alcohol that at every turn adds is 10 times of total medical material amount, the each extraction 3 hours, filter, merging filtrate gets ethanol extract B;
(3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.20 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), standing 24h filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.12 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract;
(4) taking polyethylene glycol 4000 and polyethylene glycol 6000 mix, 80 ℃ of heating in water bath make and melt to get substrate, get the principal agent extract that obtains in step (3), add the micropowder silica gel mix homogeneously, the volatile oil that obtains in the principal agent extract that mixes and step (1) is joined melt in good substrate, mixing, 80 ℃ of insulations, the speed of 30 droplets/minute splashes in cooling dimethicone 100, adopt the mode of segmentation condensation, 20 ℃, liquid coolant top, the bottom is not higher than 5 ℃, dripping becomes ball, and get final product.
In the present invention, the pass of weight portion and parts by volume is g/ml or kg/l.
Bawei Chenxiang drop pill of the present invention is compared with prior art Bawei Chenxiang ball has following characteristics:
1. according to the physicochemical property of plant amedica ingredient, carried out respectively the volatile oil extraction, ethanol extraction, water extraction has been removed invalid impurity, has reduced dose, has accelerated onset speed.
2. will contain the volatile oil medical material and carry out supercritical carbon dioxide extraction, improve the yield of volatile oil, strengthen the preparation curative effect.
3. after volatile oil disperses by the Polyethylene Glycol solid, play the inclusion essential oil effect, the stability of volatile oil is improved.
4. introducing micropowder silica gel reduces viscosity.
Following experimental example and embodiment are used for further illustrating but being not limited to the present invention.
The craft screening experiment of experimental example 1. Bawei Chenxiang drop pill
One, Bawei Chenxiang drop pill Extraction Process of Volatile Oil experiment
Extracting method is as follows:
Get Lignum Aquilariae Resinatum, Semen Myristicae, Olibanum, the Radix Aucklandiae 4 flavor medical materials by the crude drug composition and ratio appropriate, cross 40 mesh sieves after pulverizing, mix homogeneously, use carbon dioxide supercritical fluid extraction volatile oil, be placed in extraction kettle, the heating extraction kettle is after reaching predetermined temperature, send into the carbon dioxide of certain flow rate, regulate the extraction that circulates after each still pressure.
1, the impact of extracting pressure on oil yield
During test, setting extraction temperature is 45 ℃, and extraction time is 2 hours, investigates extracting pressure to the impact of oil yield, and result of the test is seen Fig. 1.
Conclusion: can be got by Fig. 1, when extracting pressure 25MPa, oil yield is the highest, therefore preferred extracting pressure is 25MPa.
2, the impact of extraction temperature on oil yield
During test, set extracting pressure position 25MPa, extraction time is 2 hours, investigates extraction temperature to the impact of oil yield, and result of the test is seen Fig. 2.
Conclusion: can be got by Fig. 2, along with the rising of temperature, oil yield also increases, but when arriving 40 ℃, oil-collecting ratio is higher, and is slightly low with the oil-collecting ratio of 45 ℃, 50 ℃, but there is no obvious difference, therefore determines 40 ℃ of final extraction temperature of conduct.
3, the impact of extraction time on oil yield
Based on above experimental data, the setting extracting pressure is 25MPa, and extraction temperature is 40 ℃, investigates extraction time to the impact of oil yield.Result of the test is seen Fig. 3.
Conclusion: can be got by Fig. 3, prolongation in time, oil yield increases thereupon, though and the oil yield of 2.5 hours and 3.0 hours is different, difference is little, considers from energy-saving and cost-reducing aspect, determines that extraction time is 2.5 hours.
In sum, the process conditions of preferred carbon dioxide supercritical fluid extraction volatile oil are: extracting pressure 25MPa, 40 ℃ of extraction temperature, extraction time 2.5 hours.
The adjuvant screening experiment of experimental example 2. Bawei Chenxiang drop pill
1. the screening experiment of Basic compose
Character according to the prescription Chinese medicine, the present invention selects water miscible Macrogol 4000 and polyethylene glycol 6000 as substrate, when preliminary experiment is selected separately Macrogol 4000 (PEG4000) or select separately polyethylene glycol 6000 (PEG6000) drop pill molding effect relatively poor, therefore select that both mixture is as substrate, result of the test sees Table 1.
The impact of table 1 substrate on the drop pill mouldability
| PEG4000：PEG6000 | Viscosity | Drop pill molding situation | Drop pill hardness |
| 1:1 | Thickness | Drop pill easily trails | Hardness is large |
| 2:1 | Thicker | Drop pill is oblate spheroid, and conditions of streaking is arranged | Hardness is larger |
| 3:1 | Moderate | The drop pill roundness is good, smooth surface | Hardness is moderate |
| 4:1 | Rarer | The easy adhesion of drop pill | Hardness is less |
Conclusion: can be got by table 1 data, in substrate, when Macrogol 4000 and polyethylene glycol 6000 ratio were 3:1, during melting, viscosity was good, and made drop pill roundness is good, smooth surface, and without hangover and cavitation, molding is better.
2. the research of principal agent extract and substrate composition
Crude drug forms and consumption is: Lignum Aquilariae Resinatum 100 weight portions, Semen Myristicae 100 weight portions, Fructus Choerospondiatis 100 weight portions, Fructus Chebulae's 100 weight portions, Olibanum 50 weight portions, the Radix Aucklandiae 175 weight portions, Flos Bombacis Malabarici 75 weight portions, Tufa 50 weight portions.
(1) get Lignum Aquilariae Resinatum, Semen Myristicae, Olibanum, the Radix Aucklandiae 4 flavor pulverizing medicinal materials by the crude drug composition and ratio and cross 40 mesh sieves, adopt supercritical carbon dioxide extraction method to extract volatile oil, get volatile oil standby, with twice of the medicinal residues extracting in water that extracts after volatile oil, add for the first time 8 times of water gagings and extracted 2 hours, add for the second time 6 times of water gagings and extracted 2 hours, merging filtrate, filter, get aqueous extract A and medicinal residues A ＇;
(2) get Fructus Choerospondiatis, Fructus Chebulae, Flos Bombacis Malabarici, Tufa totally 4 flavor medical materials by the crude drug composition and ratio, mix with the medicinal residues A ＇ that step (1) obtains, the alcohol reflux 2 times that adds volume fraction 50%, the amount of alcohol that adds for the first time is 10 times of total medical material amount, the amount of alcohol that adds for the second time is 8 times of total medical material amount, the each extraction 2 hours filters, and merging filtrate gets ethanol extract B;
(3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.18 ~ 1.25 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), hold over night filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.08 ~ 1.12 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract;
Get a certain amount of principal agent extract, (quality is than Macrogol 4000: polyethylene glycol 6000=3:1), complexity that medicine mixes with substrate and the molding situation of drop pill are investigated in melting to add respectively not commensurability mixed-matrix.
Table 2 medicine and substrate composition investigation table
| The ratio of medicine and substrate | Medicine and substrate merge situation | Viscosity | The dripping situation |
| 1:1 | Time of fusion is long, is the bulk of thickness | Thickness too | Dripping drop pill not |
| 1:2 | More easily merge | Thicker | External form is rounding not, easily hangover |
| 1:3 | Easily merge | Moderate | The drop pill forming, smooth surface |
| 1:4 | Easily merge | Moderate | The drop pill forming, smooth surface |
Conclusion: can be got by table 2, when the ratio of medicine and substrate was 1:3 and 1:4, the amalgamation of medicine and substrate was better, and viscosity is suitable, is easy to dripping, and the drop pill mouldability is better, but considered and should reduce dose as far as possible, and selecting principal agent and substrate ratio is that 1:3 is more suitable.
Experimental example 3. preparation process screening experiment
1, the research of dripping temperature
(Macrogol 4000: polyethylene glycol 6000=3:1) is the ratio of 1:3 in medicine and substrate, take appropriate amount of drug and substrate, substrate is placed in respectively in 80 ℃, 85 ℃, 90 ℃ different water-baths is heated to dissolve fully, add again medicine, stirring makes and is uniformly dispersed, prepare respectively drop pill, and check its weight differential and roundness, the results are shown in Table 3.
The impact of table 3 dripping temperature on drop pill
| Temperature (± 2 ℃) | Average ball heavy (g) | RSD（%） | Roundness |
| 80 | 0.0453 | 1.72 | Roundness is better |
| 85 | 0.0403 | 1.09 | Roundness is good, smooth surface |
| 90 | 0.0348 | 2.61 | Roundness is better |
Conclusion: can be got by table 3, with the rising of temperature, ball heavily diminishes, and in the time of 85 ℃, the drop pill weight differential is less, and roundness is good.Therefore select 85 ℃ as the dripping temperature of drop pill.
2, the research of dripping speed
(Macrogol 4000: polyethylene glycol 6000=3:1) is the ratio of 1:3 in medicine and substrate, take appropriate amount of drug and substrate, substrate is placed in 85 ℃ of water-baths is heated to dissolve fully, add again medicine, stirring makes and is uniformly dispersed, respectively with 20 droplets/minute, 30 droplets/minute, 40 droplets/minute preparation drop pill, and check its weight differential and roundness, the results are shown in Table 4.
The impact of table 4 dripping speed on drop pill
| Drip speed (droplet/minute) | Average ball heavy (g) | RSD（%） | |
| 20 | 0.0431 | 1.63 | Drop pill has conditions of streaking |
| 30 | 0.0403 | 1.51 | Roundness is good, |
| 40 | 0.0381 | 1.94 | Roundness is better |
Conclusion: can be got by table 4, along with an increase of dripping speed, drop pill weight presents the trend that reduces, and drips speed when slow, and drop is long in the mouth of pipe time of staying, is prone to conditions of streaking, and drips fastly when too fast, and the drop pill roundness is relatively poor, is 30 droplets/minute therefore select a speed.
3, the research of condensation temperature
Through preliminary experiment research, adopt single temperature condensation, when condensate temperature was high, the drop pill sedimentation velocity was fast, easily caused adhesion; And temperature is when low, and the drop pill mouldability is bad, therefore adopt the mode of segmentation condensation, namely the condensed fluid upper temp is high, and temperature of lower is low.Experimental result sees Table 5 and table 6.
The impact of table 5 condensed fluid upper temp on drop pill
| The condensed fluid upper temp (℃) | The drop pill sedimentation velocity | Drop |
| 15 | Slightly slow | Roundness is better |
| 20 | Moderate | Roundness is good |
| 25 | Comparatively fast | The easy adhesion of drop pill |
Annotate: during test, the condensed fluid temperature of lower is selected 5 ℃.
The impact of table 6 condensed fluid temperature of lower on drop pill
| The condensed fluid temperature of lower (℃) | The drop pill sedimentation velocity | Drop pill molding situation |
| ≤5 | Moderate | Roundness is good |
| 10 | Generally | Roundness is better |
| 20 | Comparatively fast | The easy adhesion of drop pill |
Annotate: during test, the condensed fluid upper temp is selected 20 ℃.
Conclusion: can be got by table 5, table 6, condensed fluid selects segmentation condensing mode effect better, and wherein preferred condensation temperature is: 20 ℃, top, bottom≤5 ℃.
The stability experiment of experimental example 4. Bawei Chenxiang drop pill
(1) preferred a kind of medicament composition dropping pills for the treatment of myocardial ischemia is made by the supplementary material of following weight portion:
(2) get volatile oil 0.3g and add beta cyclodextrin and carry out enclose, prepare altogether volatile oil clathrate compound 1.95g.Prepare drop pill according to following prescription.
Can draw by above two prescriptions, when after inclusion essential oil, gained drop pill adjuvant amount is obviously greater than enclose not, so preferably not enclose volatile oil form as prescription obvious advantage arranged.
Make respectively drop pill by prescription (1) and prescription (2), investigate the stability of drop pill, its data are as shown in table 7:
Table 7 volatile oil content stability study
Conclusion: can be got by table 7, after the prepared drop pill of enclose volatile oil and enclose, the prepared drop pill stability difference of volatile oil is not little.And volatile oil is when using beta-cyclodextrin inclusion compound, and its inclusion essential oil rate is generally in 85% left and right, loses morely, and when enclose did not directly prepare drop pill, loss of volatile oil was less, so the preferred not volatile oil of enclose carries out the dripping drop pill.
Experimental example 5. disintegrate experiments
By inspection technique disintegration (appendix XII A of Pharmacopoeia of the People's Republic of China version in 2010), Bawei Chenxiang ball and Bawei Chenxiang drop pill have been carried out the disintegration time test relatively, result of the test such as following table 8.
The Bawei Chenxiang ball is scolded Tibetan medicine limited company by gold and is produced, lot number: 20120101
The Bawei Chenxiang drop pill is pressed embodiment 2 self-control samples, lot number: 20120403
Table 8 drop pill disintegration time investigation table
Conclusion: can be got by table 8, the disintegration time of Bawei Chenxiang drop pill obviously is better than the Bawei Chenxiang ball.
The clinical experiment of experimental example 6. Bawei Chenxiang drop pill
One, data and method
1, inclusion criteria: include case in by diagnostic criteria for coronary heart disease, choose and meet inclusion criteria patient 126 examples, be divided at random 3 groups.The physical data such as 3 groups of Genders, age, the course of disease, long-term prescription have comparability through check difference not statistically significant (P＞0.05).Wherein, 27 examples of being in hospital, outpatient service 99 examples; Male's 81 examples, women's 45 examples; 40 years old-69 years old age, average 56.8 years old; Course of disease 7d to 12 year, average 2,16 years.
2, Therapeutic Method: the patient of 126 routine coronary heart disease and myocardial ischemias is divided into 3 groups at random.1 group (43 example) adds on the routine medication basis and uses the Bawei Chenxiang ball, 3 treatments every day; 2 groups (41 example) adds the Bawei Chenxiang drop pill of embodiment 2 on the routine medication basis, 3 treatments every day; 3 groups (42 examples) are matched group, only use routine medication, adopt aspirin or the treatments such as clopidogrel, metoprolol, Statins fat regulation medicine and angiotensin converting enzyme inhibitor (ACEI) or angiotensin ii receptor antagonist (ARB) class.4 weeks were 1 course for the treatment of.
3, detect index: carry out semiography and untoward reaction (dizzy, nauseating, stomachache, hemorrhage) registration before and after treatment; 12 lead Electrocardiography; The chemical examination liver function: glutamate pyruvate transaminase (GPT), glutamic oxaloacetic transaminase, GOT (GOT), gamma glutamyl transpeptidase (γ-GT); Chemical examination liver function: creatinine (Cr), bladder chalone C (Cy-c), urinaryalbumin (U-Pro); Index of correlation is analyzed.
4, symptom criterion of therapeutical effect: produce effects: original uncomfortable in chest or angina pectoris symptom disappears and does not reaccess; Effectively: sx↓ or seizure frequency reduce more than 50%; Invalid: symptom is without significant change (comprising the front asymptomatic person for the treatment of); Increase the weight of: the more obvious or seizure frequency of symptom increases.
5, electrocardiogram improves standard: produce effects: abnormal ischemic ST force down with or the T ripple be inverted and recover normal or have clear improvement; Effectively: abnormal ST section and T ripple make moderate progress; Invalid: electrocardiogram unchanged (before comprising treatment, electrocardiogram is as good as normal person) before and after treatment; Increase the weight of: electrocardiographic abnormality is more obvious.
6, Excluded cases standard: acute myocardial infarction and other heart disease, in nerve functional disease, Climacteric, cervical spondylosis due to chest pain person; Merge the above hypertension of moderate, severe pulmonary insufficiency, the serious protopathy such as liver, kidney hemopoietic system, psychotic.Below 45 years old or more than 68 years old, gestation or women breast-feeding their children have allergy sufferers to this product; Not medication in accordance with regulations can't judge the not congruent patient of affecting the treatment of curative effect or data.
7, observation index: observe treatment front and back clinical symptoms outbreak situation, electrocardiogram situation of change, chemical examination hepatic and renal function situation of change and untoward reaction etc.The number of cases that after untoward reaction statistics treatment, related symptoms increases wherein hemorrhagely comprises hematuria new during treatment, has blood in stool, gingiva and conjunctival hemorrhage.
8, statistical procedures: adopt SPSS12.0 software to carry out statistical analysis, enumeration data represents with rate, adopts inspection χ 2 to test.
Two, result
1, after 3 groups of symptom curative effects relatively treated for 4 weeks, 3 groups of subjective symptomss have clear improvement.See table 1 for details.
Table 9 group symptom curative effect relatively
Obvious effective rate=produce effects/n * 100%; Total effective rate=(produce effects+effectively)/n * 100%.
The present invention is through improving the new compositions of development on the basis of former Bawei Chenxiang ball, on the basis that keeps original drug form curative effect, the characteristic that has kept Tibetan medicine, by above, the clinical symptoms effectiveness study result of Tibetan medicinal composition in the present invention to curing myocardial ischemia shown, 1 group of (embodiment 2 compositions Bawei Chenxiang drop pill treatment groups) total effective rate 82.9%, 69.8%, 3 group of (matched group) total effective rate 50.0% of 2 groups of (Bawei Chenxiang pill for curing group) total effective rates; 39.0%, 3 group of (matched group) obvious effective rate 21.4% of 1 group of 30.2%, 2 group of (Bawei Chenxiang pill for curing group) obvious effective rate of (embodiment 2 compositions Bawei Chenxiang drop pill treatment groups) obvious effective rate.1 group, 2 groups with 3 groups relatively, through the Ridit check, between P＜0.05, two group, relatively there were significant differences, 1 group, 2 groups therapeutic effect are better than 3 groups; 2 groups with 1 group relatively, through the Ridit check, between P＜0.05, two group, relatively there were significant differences, 2 groups of curative effects are higher than 1 group, prompting embodiment 2 Bawei Chenxiang drop pill curative effects are better than the Bawei Chenxiang ball.
2,3 groups of electrocardiograms improve relatively (seeing Table 2)
Table 10 electrocardiogram improves relatively
Obvious effective rate=produce effects/n * 100%; Total effective rate=(produce effects+effectively)/n * 100%.
The present invention is through improving the new compositions of development on the basis of former Bawei Chenxiang ball, on the basis that keeps original drug form curative effect, the characteristic that has kept Tibetan medicine, by above, the electrocardiogram effectiveness study result of Tibetan medicinal composition in the present invention to curing myocardial ischemia shown, 1 group of (embodiment 2 compositions Bawei Chenxiang drop pill treatment groups) total effective rate 55.8%, 75.6%, 3 group of (matched group) total effective rate 45.2% of 2 groups of (Bawei Chenxiang pill for curing group) total effective rates; 31.7%, 3 group of (matched group) obvious effective rate 11.9% of 1 group of 23.3%, 2 group of (Bawei Chenxiang pill for curing group) obvious effective rate of (embodiment 2 compositions Bawei Chenxiang drop pill treatment groups) obvious effective rate.1 group, 2 groups with 3 groups relatively, through the Ridit check, between P＜0.05, two group, relatively there were significant differences, 1 group, 2 groups therapeutic effect are better than 3 groups; 2 groups with 1 group relatively, through the Ridit check, between P＜0.05, two group, relatively there were significant differences, 2 groups of curative effects are higher than 1 group, prompting embodiment 2 flavor Lignum Aquilariae Resinatum drop pill curative effects are better than the Bawei Chenxiang ball.
3,3 groups of hepatic and renal functions and untoward reaction not statistically significant relatively before and after hepatic and renal function and untoward reaction a situation arises treatment.See Table 3.
Before and after the treatment of table 113 group, hepatic and renal function reaches relatively (notes: P＞0.05) of untoward reaction extremely
Three, discussion of results
Experimental result shows: Bawei Chenxiang ball and embodiment 2 Bawei Chenxiang drop pill are being alleviated uncomfortable in chest and angina pectoris symptom, are being improved the aspect such as myocardial ischemia and obviously be better than alone conventional western medicine, and embodiment 2 Bawei Chenxiang drop pill curative effects are better than the Bawei Chenxiang ball.And do not find hepatorenal damage and untoward reaction.
Description of drawings
The affect figure of Fig. 1 extracting pressure on oil yield.
The affect figure of Fig. 2 extraction temperature on oil yield.
The affect figure of Fig. 3 extraction time on oil yield.
The specific embodiment
The following example and experimental example are used for further illustrating but being not limited to the present invention.
A kind of Bawei Chenxiang drop pill is made by the supplementary material of following weight portion:
Principal agent extract 112g,
Volatile oil 21ml,
Macrogol 4000 300g,
Polyethylene glycol 6000 100g,
Micropowder silica gel 26.7g.
Be prepared as follows and form:
(1) get Lignum Aquilariae Resinatum 100 weight portions, Semen Myristicae 100 weight portions, Olibanum 50 weight portions, the Radix Aucklandiae 175 weight portions 4 flavor pulverizing medicinal materials by the crude drug composition and ratio and cross 40 mesh sieves, adopt supercritical carbon dioxide extraction method to extract volatile oil, extracting pressure 25MPa, 40 ℃ of extraction temperature, extraction time 2.5 hours, get volatile oil standby, with twice of the medicinal residues extracting in water that extracts after volatile oil, adding for the first time 8 times of water gagings extracted 2 hours, adding for the second time 6 times of water gagings extracted 2 hours, merging filtrate filters, and gets aqueous extract A and medicinal residues A ＇;
(2) get Fructus Choerospondiatis 100 weight portions, Fructus Chebulae's 100 weight portions, Flos Bombacis Malabarici 75 weight portions, Tufa 50 weight portions totally 4 flavor medical materials by the crude drug composition and ratio, mix with the medicinal residues A ＇ that step (1) obtains, the alcohol reflux 2 times that adds volume fraction 50%, the amount of alcohol that adds for the first time is 10 times of total medical material amount, the amount of alcohol that adds for the second time is 8 times of total medical material amount, the each extraction 2 hours filters, and merging filtrate gets ethanol extract B;
(3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.25 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), standing 20h filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.08 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract;
(4) taking polyethylene glycol 4000 and polyethylene glycol 6000,80 ℃ of heating in water bath make and melt to get substrate, get the principal agent extract that obtains in step (3), add the micropowder silica gel mix homogeneously, the volatile oil in the principal agent extract that mixes and step (1) is joined melt in good substrate, mixing, 85 ℃ of insulations, the speed of 30 droplets/minute splashes in cooling dimethicone 100, and dripping becomes ball, and get final product.
A kind of Bawei Chenxiang drop pill is made by the supplementary material of following weight portion:
Principal agent extract 135g,
Volatile oil 25ml,
Macrogol 4000 360g,
Polyethylene glycol 6000 120g,
Micropowder silica gel 32g.
Be prepared as follows and form:
(1) get Lignum Aquilariae Resinatum 100 weight portions, Semen Myristicae 100 weight portions, Olibanum 50 weight portions, the Radix Aucklandiae 175 weight portions 4 flavor pulverizing medicinal materials by the crude drug composition and ratio and cross 30 sieves, adopt supercritical carbon dioxide extraction method to extract volatile oil, extracting pressure 30MPa, 50 ℃ of extraction temperature, extraction time 3 hours, get volatile oil standby, medicinal residues extracting in water 3 times with extracting after volatile oil adds 8 times of water gagings at every turn and extracted 3 hours, merging filtrate, filter, get aqueous extract A and medicinal residues A ＇;
(2) get Fructus Choerospondiatis 100 weight portions, Fructus Chebulae's 100 weight portions, Flos Bombacis Malabarici 75 weight portions, Tufa 50 weight portions totally 4 flavor medical materials by the crude drug composition and ratio, mix with the medicinal residues A ＇ that step (1) obtains, the alcohol reflux 3 times that adds volume fraction 40%, the amount of alcohol that at every turn adds is 10 times of total medical material amount, the each extraction 3 hours, filter, merging filtrate gets ethanol extract B;
(3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.20 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), standing 24h filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.12 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract;
(4) taking polyethylene glycol 4000 and polyethylene glycol 6000 mix, 80 ℃ of heating in water bath make and melt to get substrate, get the principal agent extract that obtains in step (3), add the micropowder silica gel mix homogeneously, the volatile oil that obtains in the principal agent extract that mixes and step (1) is joined melt in good substrate, mixing, 80 ℃ of insulations, the speed of 30 droplets/minute splashes in cooling dimethicone 100, adopt the mode of segmentation condensation, 20 ℃, liquid coolant top, the bottom is not higher than 5 ℃, dripping becomes ball, and get final product.
Embodiment 3, Bawei Chenxiang drop pill of the present invention
Principal agent extract 169g,
Volatile oil 31ml,
Macrogol 4000 450g,
Polyethylene glycol 6000 150g,
Micropowder silica gel 40g.
Be prepared as follows and form:
(1) get Lignum Aquilariae Resinatum 100 weight portions, Semen Myristicae 100 weight portions, Olibanum 50 weight portions, the Radix Aucklandiae 175 weight portions 4 flavor pulverizing medicinal materials by the crude drug composition and ratio and cross 40 mesh sieves, adopt supercritical carbon dioxide extraction method to extract volatile oil, extracting pressure 25MPa, 40 ℃ of extraction temperature, extraction time 2.5 hours, get volatile oil standby, with twice of the medicinal residues extracting in water that extracts after volatile oil, adding for the first time 8 times of water gagings extracted 2 hours, adding for the second time 6 times of water gagings extracted 2 hours, merging filtrate filters, and gets aqueous extract A and medicinal residues A ＇;
(2) get Fructus Choerospondiatis 100 weight portions, Fructus Chebulae's 100 weight portions, Flos Bombacis Malabarici 75 weight portions, Tufa 50 weight portions totally 4 flavor medical materials by the crude drug composition and ratio, mix with the medicinal residues A ＇ that step (1) obtains, the alcohol reflux 2 times that adds volume fraction 50%, the amount of alcohol that adds for the first time is 10 times of total medical material amount, the amount of alcohol that adds for the second time is 8 times of total medical material amount, the each extraction 2 hours filters, and merging filtrate gets ethanol extract B;
(3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.25 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), standing 20h filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.08 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract;
(4) taking polyethylene glycol 4000 and polyethylene glycol 6000,80 ℃ of heating in water bath make and melt to get substrate, get the principal agent extract that obtains in step (3), add the micropowder silica gel mix homogeneously, volatile oil in the principal agent extract that mixes and step (1) is joined melt in good substrate, mixing is 85 ℃ of insulations, the speed of 30 droplets/minute splashes in cooling dimethicone 100, adopt the mode of segmentation condensation, 20 ℃, liquid coolant top, the bottom is not higher than 5 ℃, dripping becomes ball, and get final product.
Claims (6)
1. a medicament composition dropping pills for the treatment of myocardial ischemia, is characterized in that, made by the raw material of following weight portion:
Principal agent extract 112-169 weight portion,
Volatile oil 21-31 parts by volume,
Macrogol 4000 300-450 weight portion,
Polyethylene glycol 6000 100-150 weight portion,
Micropowder silica gel 27-40 weight portion;
The unit of above weight portion and parts by volume is: g/ml or kg/l;
Described principal agent extract and volatile oil make as follows: (1) is got Lignum Aquilariae Resinatum 100 weight portions, Semen Myristicae 100 weight portions, Olibanum 50 weight portions, the Radix Aucklandiae 175 weight portions 4 flavor pulverizing medicinal materials by the crude drug composition and ratio and is crossed the 30-50 mesh sieve, adopt supercritical carbon dioxide extraction method to extract volatile oil, extracting pressure 25-30MPa, extraction temperature 40-50 ℃, extraction time 2.5-3 hour, get volatile oil standby; Medicinal residues extracting in water 2-3 time with extracting after volatile oil adds 6-8 times of water gaging at every turn and extracted 2-3 hour, merging filtrate, and filtration gets aqueous extract A and medicinal residues A ＇; (2) get Fructus Choerospondiatis 100 weight portions, Fructus Chebulae's 100 weight portions, Flos Bombacis Malabarici 75 weight portions, Tufa 50 weight portions totally 4 flavor medical materials by the crude drug composition and ratio, mix with the medicinal residues A ＇ that step (1) obtains, alcohol reflux 2-3 time that adds volume fraction 40%-50%, the amount of alcohol that at every turn adds is 8-10 times of total medical material amount, the each extraction 2-3 hour, filter, merging filtrate gets ethanol extract B; (3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.18 ~ 1.25 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), standing 12-24h filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.08 ~ 1.12 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract.
2. a kind of medicament composition dropping pills for the treatment of myocardial ischemia as claimed in claim 1, is characterized in that, made by the raw material of following weight portion:
Principal agent extract 131-150 weight portion,
Volatile oil 24-28 parts by volume,
Macrogol 4000 350-400 weight portion,
Polyethylene glycol 6000 117-133 weight portion,
Micropowder silica gel 31-36 weight portion.
3. a kind of medicament composition dropping pills for the treatment of myocardial ischemia as claimed in claim 2, is characterized in that, made by the raw material of following weight portion:
Principal agent extract 135g,
Volatile oil 25ml,
Macrogol 4000 360g,
Polyethylene glycol 6000 120g,
Micropowder silica gel 32g;
described principal agent extract and volatile oil make as follows: (1) gets Lignum Aquilariae Resinatum 100g by the crude drug composition and ratio, Semen Myristicae 100g, Olibanum 50g, Radix Aucklandiae 175g4 flavor pulverizing medicinal materials is crossed 40 mesh sieves, adopt supercritical carbon dioxide extraction method to extract volatile oil, extracting pressure 25MPa, 40 ℃ of extraction temperature, extraction time 2.5 hours, get volatile oil standby, with twice of the medicinal residues extracting in water that extracts after volatile oil, adding for the first time 8 times of water gagings extracted 2 hours, adding for the second time 6 times of water gagings extracted 2 hours, merging filtrate, filter, get aqueous extract A and medicinal residues A ＇, (2) get Fructus Choerospondiatis 100g, Fructus Chebulae 100g, Flos Bombacis Malabarici 75g, Tufa 50g totally 4 flavor medical materials by the crude drug composition and ratio, mix with the medicinal residues A ＇ that step (1) obtains, the alcohol reflux 2 times that adds volume fraction 50%, the amount of alcohol that adds for the first time is 10 times of total medical material amount, the amount of alcohol that adds for the second time is 8 times of total medical material amount, the each extraction 2 hours filters, and merging filtrate gets ethanol extract B, (3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.25 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), standing 20h filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.08 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract.
4. a kind of preparation method for the treatment of the medicament composition dropping pills of myocardial ischemia as claimed in claim 1 or 2, is characterized in that, step is as follows:
(1) get Lignum Aquilariae Resinatum 100 weight portions, Semen Myristicae 100 weight portions, Olibanum 50 weight portions, the Radix Aucklandiae 175 weight portions 4 flavor pulverizing medicinal materials by the crude drug composition and ratio and cross the 30-50 mesh sieve, adopt supercritical carbon dioxide extraction method to extract volatile oil, extracting pressure 25-30MPa, extraction temperature 40-50 ℃, extraction time 2.5-3 hour, get volatile oil standby, with medicinal residues extracting in water 2-3 time that extracts after volatile oil, add 6-8 times of water gaging extracted 2-3 hour at every turn, merging filtrate, filter, get aqueous extract A and medicinal residues A ＇;
(2) get Fructus Choerospondiatis 100 weight portions, Fructus Chebulae's 100 weight portions, Flos Bombacis Malabarici 75 weight portions, Tufa 50 weight portions totally 4 flavor medical materials by the crude drug composition and ratio, mix with the medicinal residues A ＇ that step (1) obtains, alcohol reflux 2-3 time that adds volume fraction 40%-50%, the amount of alcohol that at every turn adds is 8-10 times of total medical material amount, the each extraction 2-3 hour, filter, merging filtrate gets ethanol extract B;
(3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.18 ~ 1.25 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), standing 12-24h filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.08 ~ 1.12 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract;
(4) taking polyethylene glycol 4000 and polyethylene glycol 6000 mix, 80 ℃ of heating in water bath make and melt to get substrate, get the principal agent extract that obtains in step (3), add the micropowder silica gel mix homogeneously, the volatile oil that obtains in the principal agent extract that mixes and step (1) is joined melt in good substrate, mixing, 80 ℃ of-85 ℃ of insulations, splash in cooling dimethicone 100, dripping becomes ball, and get final product.
5. a kind of preparation method for the treatment of the medicament composition dropping pills of myocardial ischemia as claimed in claim 4, is characterized in that, step is as follows:
(1) get Lignum Aquilariae Resinatum 100 weight portions, Semen Myristicae 100 weight portions, Olibanum 50 weight portions, the Radix Aucklandiae 175 weight portions 4 flavor pulverizing medicinal materials by the crude drug composition and ratio and cross 40 mesh sieves, adopt supercritical carbon dioxide extraction method to extract volatile oil, extracting pressure 25MPa, 40 ℃ of extraction temperature, extraction time 2.5 hours, get volatile oil standby, with twice of the medicinal residues extracting in water that extracts after volatile oil, adding for the first time 8 times of water gagings extracted 2 hours, adding for the second time 6 times of water gagings extracted 2 hours, merging filtrate filters, and gets aqueous extract A and medicinal residues A ＇;
(2) get Fructus Choerospondiatis 100 weight portions, Fructus Chebulae's 100 weight portions, Flos Bombacis Malabarici 75 weight portions, Tufa 50 weight portions totally 4 flavor medical materials by the crude drug composition and ratio, mix with the medicinal residues A ＇ that step (1) obtains, the alcohol reflux 2 times that adds volume fraction 50%, the amount of alcohol that adds for the first time is 10 times of total medical material amount, the amount of alcohol that adds for the second time is 8 times of total medical material amount, the each extraction 2 hours filters, and merging filtrate gets ethanol extract B;
(3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.25 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), standing 20h filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.08 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract;
(4) taking polyethylene glycol 4000 and polyethylene glycol 6000,80 ℃ of heating in water bath make and melt to get substrate, get the principal agent extract that obtains in step (3), add the micropowder silica gel mix homogeneously, volatile oil in the principal agent extract that mixes and step (1) is joined melt in good substrate, mixing is 85 ℃ of insulations, the speed of 30 droplets/minute splashes in cooling dimethicone 100, adopt the mode of segmentation condensation, 20 ℃, liquid coolant top, the bottom is not higher than 5 ℃, dripping becomes ball, and get final product.
6. a kind of preparation method for the treatment of the medicament composition dropping pills of myocardial ischemia as claimed in claim 4, is characterized in that, step is as follows:
(1) get Lignum Aquilariae Resinatum 100 weight portions, Semen Myristicae 100 weight portions, Olibanum 50 weight portions, the Radix Aucklandiae 175 weight portions 4 flavor pulverizing medicinal materials by the crude drug composition and ratio and cross 30 sieves, adopt supercritical carbon dioxide extraction method to extract volatile oil, extracting pressure 30MPa, 50 ℃ of extraction temperature, extraction time 3 hours, get volatile oil standby, medicinal residues extracting in water 3 times with extracting after volatile oil adds 8 times of water gagings at every turn and extracted 3 hours, merging filtrate, filter, get aqueous extract A and medicinal residues A ＇;
(2) get Fructus Choerospondiatis 100 weight portions, Fructus Chebulae's 100 weight portions, Flos Bombacis Malabarici 75 weight portions, Tufa 50 weight portions totally 4 flavor medical materials by the crude drug composition and ratio, mix with the medicinal residues A ＇ that step (1) obtains, the alcohol reflux 3 times that adds volume fraction 40%, the amount of alcohol that at every turn adds is 10 times of total medical material amount, the each extraction 3 hours, filter, merging filtrate gets ethanol extract B;
(3) the ethanol extract B that obtains in the aqueous extract A that obtains in step (1) and step (2) is merged, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.20 thick paste, add ethanol, make the alcohol amount of containing reach 70%(v/v), standing 24h filters filtrate recycling ethanol, 60 ℃ are evaporated to 50 ℃ to measure relative densities are 1.12 thick paste, 60 ℃ of drying under reduced pressure, pulverize winner's medicament extract;
(4) taking polyethylene glycol 4000 and polyethylene glycol 6000 mix, 80 ℃ of heating in water bath make and melt to get substrate, get the principal agent extract that obtains in step (3), add the micropowder silica gel mix homogeneously, the volatile oil that obtains in the principal agent extract that mixes and step (1) is joined melt in good substrate, mixing, 80 ℃ of insulations, the speed of 30 droplets/minute splashes in cooling dimethicone 100, adopt the mode of segmentation condensation, 20 ℃, liquid coolant top, the bottom is not higher than 5 ℃, dripping becomes ball, and get final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310063989.6A CN103127309B (en) | 2013-02-28 | 2013-02-28 | Eight-medicine composition Chinese Eaglewood dropping pill for treating myocardial ischemia, and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310063989.6A CN103127309B (en) | 2013-02-28 | 2013-02-28 | Eight-medicine composition Chinese Eaglewood dropping pill for treating myocardial ischemia, and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103127309A true CN103127309A (en) | 2013-06-05 |
| CN103127309B CN103127309B (en) | 2015-01-07 |
Family
ID=48488179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310063989.6A Active CN103127309B (en) | 2013-02-28 | 2013-02-28 | Eight-medicine composition Chinese Eaglewood dropping pill for treating myocardial ischemia, and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103127309B (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101234120A (en) * | 2008-03-04 | 2008-08-06 | 王玉良 | Notoginseng dropping pills and preparation method thereof |
| CN101554466A (en) * | 2009-05-19 | 2009-10-14 | 赤峰天奇制药有限责任公司 | Drug for treating coronary heart disease |
| CN101744849A (en) * | 2008-12-18 | 2010-06-23 | 海南中化联合制药工业有限公司 | Glabrous sarcandra herb dripping pill and preparation technology |
| CN101953810A (en) * | 2009-07-14 | 2011-01-26 | 北京亚东生物制药有限公司 | Breviscapine pill |
| CN102526353A (en) * | 2012-03-15 | 2012-07-04 | 山东阿如拉药物研究开发有限公司 | Method for preparing medicinal composition preparation for treating myocardial ischemia |
-
2013
- 2013-02-28 CN CN201310063989.6A patent/CN103127309B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101234120A (en) * | 2008-03-04 | 2008-08-06 | 王玉良 | Notoginseng dropping pills and preparation method thereof |
| CN101744849A (en) * | 2008-12-18 | 2010-06-23 | 海南中化联合制药工业有限公司 | Glabrous sarcandra herb dripping pill and preparation technology |
| CN101554466A (en) * | 2009-05-19 | 2009-10-14 | 赤峰天奇制药有限责任公司 | Drug for treating coronary heart disease |
| CN101953810A (en) * | 2009-07-14 | 2011-01-26 | 北京亚东生物制药有限公司 | Breviscapine pill |
| CN102526353A (en) * | 2012-03-15 | 2012-07-04 | 山东阿如拉药物研究开发有限公司 | Method for preparing medicinal composition preparation for treating myocardial ischemia |
Non-Patent Citations (1)
| Title |
|---|
| 景舒等: ""正交实验法优选清心沉香八味滴丸制备工艺"", 《时珍国医国药》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103127309B (en) | 2015-01-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101554466B (en) | Drug for treating coronary heart disease | |
| CN107714949A (en) | Dendrobium candidum is preparing the application process in treating hypertension drug | |
| CN103006838B (en) | Traditional Chinese medicine composition for treating cardiovascular and cerebrovascular diseases | |
| CN103520278B (en) | A kind of have Chinese medicine granules of QI invigorating warming YANG effect and preparation method thereof | |
| CN1318083C (en) | Chinese patent medicine for preventing and treating apoplexia disease, and its production method and use | |
| CN106138668B (en) | A kind of Chinese medicine composition and preparation method thereof for treating Chronic Obstructive Pulmonary Disease | |
| CN103006769A (en) | Traditional Chinese medicine composition for treating cardiovascular and cerebrovascular diseases and preparation method thereof | |
| CN102258742A (en) | Chinese medicinal medicine composition for treating depression and preparation method thereof | |
| CN110251591A (en) | A kind of pharmaceutical composition and its preparation method and application that aided blood pressure-lowering is hypoglycemic | |
| CN1958010A (en) | Composition preparation of Chinese traditional medicine, and preparation method | |
| CN103127309B (en) | Eight-medicine composition Chinese Eaglewood dropping pill for treating myocardial ischemia, and its preparation method | |
| CN1310664C (en) | Chinese medicine capsule for treating cardiac and cerebral vascular diseases and its production process | |
| CN104904909A (en) | Anti-hypertension tea bag | |
| CN101249158B (en) | Traditional Chinese medicine preparation for preventing and treating cardiovascular and cerebrovascular diseases and preparation | |
| CN1310662C (en) | Chinese medicine for coronary heart disease | |
| CN103386006B (en) | A kind of application of Chinese medicine composition in the dull-witted drug for the treatment of is prepared | |
| CN101053626B (en) | Traditional Chinese medicine for treating coronary heart disease and angina pectoris and its preparation method | |
| CN102274428B (en) | Pharmaceutical composition with effect on treating irritable bowel syndrome and preparation method and application thereof | |
| CN108704105A (en) | A kind of Chinese medicine composition for treating Acute Cerebral Infarction | |
| CN102743456B (en) | The application of a kind of Chinese medicine composition in the medicine of preparation control delayed encephalopathy after acute carbon monoxide poisoning | |
| CN107095977A (en) | A kind of medicament and its pharmaceutical formulation and preparation method with the malicious effect of fire row of dispelling | |
| CN1293971A (en) | Medicine for treating apoplexy and its preparing process | |
| CN102204956A (en) | Chinese medicinal composition used at stroke recovery period and preparation method thereof | |
| CN102416147B (en) | Medicinal composition for treating mania of patients abstained from drugs | |
| CN105687499A (en) | Betaxolol containing pharmaceutical composition for treating hypertension and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: SHANDONG JINHE DRUG RESEARCH AND DEVELOPMENT CO., Free format text: FORMER NAME: SHANDONG ARURA PHARMACEUTICAL RESEARCH + DEVELOPMENT CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 250101 Shandong city of Ji'nan province (Lixia District Shun) high wind Road No. 322 room 501-506 Patentee after: Shandong Jin He drug development research company limited Address before: 250101 Shandong city of Ji'nan province (Lixia District Shun) high wind Road No. 322 room 501-506 Patentee before: Shandong ARURA Pharmaceutical Research & Development Co., Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170719 Address after: 810003, No. two, No. 22, Xining Road, Qinghai, Qinghai Province Patentee after: JINHE TIBETAN MEDICINE CO., LTD. Address before: 250101 Shandong city of Ji'nan province (Lixia District Shun) high wind Road No. 322 room 501-506 Patentee before: Shandong Jin He drug development research company limited |