CN1931160A - Ginkgo ketone ester dropping pill and its prepn process - Google Patents
Ginkgo ketone ester dropping pill and its prepn process Download PDFInfo
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Abstract
The present invention relates to one kind of ginkgo ketone ester dripping pill and its preparation process, and belongs to the field of Chinese medicine technology. The ginkgo ketone ester dripping pill is prepared mainly with ginkgo ketone ester and medicinal matrix, which is preferably the mixture of polyglycol-4000 and polyglycol-6000. The ginkgo ketone ester dripping pill preparation has ideal treating effect on apoplexy and coronary heart disease caused by blood stasis, and possesses the advantages of quick absorption, high bioavailability, small dosage, several taking modes, low production cost, determined curative effect, etc.
Description
Technical field
The present invention relates to a kind of bilobanone ester dropping pills that is used for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof, belong to technical field of medicaments.
Technical background
Cardiovascular and cerebrovascular disease is the No.1 killer of human health, has characteristics such as high incidence, high mortality, high disability rate, as apoplexy, i.e. and apoplexy, fatality rate occupies the third place in the world, and disability rate ranks first in the world.It is reported that there is 2,600,000 people every year in China because of cardiovascular and cerebrovascular disease death at present, therefore plant disease and death with regard to 1 people is arranged per 12 seconds, so prevention and treatment cardiovascular and cerebrovascular disease become the serious and arduous problem of pendulum in face of us.And in the assault of fortified positions of this human control cerebral ischemia, ginkgo agent is a dark horse, extremely World Focusing.Along with the continuous development of medicine, chemical industry, enjoy favor in recent years especially as the main effective ingredient ginkgo flavone and lactone of Semen Ginkgo.Its preparation XINGLING KELI has the function of activating blood circulation to dissipate blood stasis, TONGMAI SHULUO, is mainly used in apoplexy, thoracic obstruction diseases such as (coronary heart disease) that blood stasis causes, and disease is seen: chest distress and palpitation symptoms, stiff tongue and retardation in speech, hemiplegia, hemianesthesia, crooked mouth and tongue, dementia etc.But because the bilobalide constituents in the ginkgo flavone and lactone is water insoluble, the aglycon constituents is also water insoluble in the flavone, and the granule of making is a mix suspension grain, and ginkgo flavone and lactone fine powder dispersion is lower, and the dissolving that influences lactone and flavonoid absorbs; Along with the continuous development of preparation technique, the new novel form that more helps disease treatment continues to bring out simultaneously, and drop pill still belongs to blank in the preparation of ginkgo flavone and lactone listing at present; In conjunction with the order of importance and emergency at disease, it is far from being enough that a preparation is only arranged again.So the present invention is directed to the deficiencies in the prior art, develop bilobanone ester dropping pills.
Summary of the invention
The object of the present invention is to provide a kind of new bilobanone ester dropping pills and preparation method thereof, ginkgo flavone and lactone promptly contains the Semen Ginkgo extrac of flavone and lactone.Because the bilobalide constituents in the ginkgo flavone and lactone is water insoluble, the aglycon constituents is also water insoluble in the flavone, thereby ginkgo flavone and lactone fine powder dispersion is lower, and ordinary preparation such as granule etc. can not absorb well owing to the low-solubility of lactone and flavonoid, make bioavailability of medicament the end of than.
We are surprised to find that employing new technique---solid dispersion technology, ginkgo flavone and lactone dissolving, suspendible, emulsifying can be become molecule or microgranule with Polyethylene Glycol.Polyethylene Glycol is the crystallinity water soluble (CO) polymers, the helix that two units are arranged in the per unit in the molecule, when medicine solidifies, the molecular weight of ginkgo flavone and lactone is lower than 500, just can be included between the spiral type of Polyethylene Glycol in the matter space, matter solid solution between the two forms is dissolved the ginkgo flavone and lactone that is scattered in wherein in Polyethylene Glycol is dissolved in the process of water, thereby has improved the dissolubility and the dissolution rate of ginkgo flavone and lactone.
Use molecular weight to be respectively one or more mixed-matrix of 4000,6000 and 8000 Macrogol 4000, polyethylene glycol 6000, Polyethylene Glycol 8000 in the present invention as disperseing to use substrate, its characteristic is a Polyethylene Glycol--after the rapid cooling of dispersion of medicine, in very short time, solidify during low temperature, utilize this characteristic that Polyethylene Glycol-ginkgo flavone and lactone dispersion is made drop pill, further increased the surface area of medicine, improved the infiltration rate and the bioavailability of ginkgo flavone and lactone, played quick-acting and effect efficiently; Drops of the present invention has reduced production cost simultaneously, is about 50% of general formulation; Polyethylene Glycol is transparent in visible light and ultraviolet ray range, can directly detect with visible light or ultraviolet in assay and dissolution test, and this quality of the pharmaceutical preparations controllability, medicine stability improve greatly; But said preparation both can oral also sublingual administration, enlarged the use crowd, and former dosage form granule was oral only, for being difficult for oral patient, can delay the state of an illness; Compare with former dosage form, active constituent content improves, and dose reduces.
The present invention finishes like this:
A kind of bilobanone ester dropping pills that is used for the treatment of cardiovascular and cerebrovascular disease, calculate according to percentage by weight, it mainly is made by ginkgo flavone and lactone 8-25%, medicinal substrate 92-75%, and described medicinal substrate is one or more mixture of Macrogol 4000, polyethylene glycol 6000, Polyethylene Glycol 8000.Specifically, calculate according to percentage by weight, it mainly is made by ginkgo flavone and lactone 15-20%, medicinal substrate 85-80%, and described drug matrices is the mixture of Macrogol 4000 and polyethylene glycol 6000.
Ginkgo flavone and lactone can be that method commercially available or that employing is conventional prepares, and wherein the content of Ginkgo total flavones must not be lower than 44%, and the content of Ginkgo total lactones must not be lower than 6.0%.
The part by weight scope is 2 in the mixed-matrix of Macrogol 4000 and polyethylene glycol 6000: 1-4: 1.Be preferably 3: 1.
Described a kind of preparation method that is used for the treatment of the bilobanone ester dropping pills of cardiovascular and cerebrovascular disease is: medicinal substrate is put in the rustless steel container, be heated to 80-110 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, be transferred in the reservoir, 70-90 ℃ of insulation, dripping the system condition is: water dropper bore 2.5-3.5mm/3.5-4.5mm, drip apart from being 4-10cm, regulate dropping liquid valve (drip speed and be about 50 of per minutes), regulate the dropping liquid valve, splash in 2-15 ℃ the liquid coolant, liquid coolant is use up and wiped to the drop pill drop that forms, collect drop pill, promptly.
Described a kind of preparation method that is used for the treatment of the bilobanone ester dropping pills of cardiovascular and cerebrovascular disease is: with Macrogol 4000, polyethylene glycol 6000 in 2: 1-4: 1 ratio is put in the rustless steel container, be heated to 90-100 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, be transferred in the reservoir, 80-85 ℃ of insulation, dripping the system condition is: water dropper bore 3mm/4mm, dripping distance is 6-8cm, regulate dropping liquid valve (drip speed and be about 50 of per minutes), splash in 5-10 ℃ the liquid coolant, to the greatest extent and wipe liquid coolant the drop pill drop that forms, collect drop pill, promptly.
Specifically, this drop pill is preparation like this: Macrogol 4000, polyethylene glycol 6000 are put in the rustless steel container in 3: 1 ratio, be heated to 90-100 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, be transferred in the reservoir, 80-85 ℃ of insulation, dripping the system condition is: water dropper bore 3mm/4mm, drip apart from being 6-8cm, and regulate dropping liquid valve (drip speed and be about 50 of per minutes), splash in 5-10 ℃ the liquid coolant, liquid coolant is use up and wiped to the drop pill drop that forms, collect drop pill, promptly.
Described liquid coolant includes but not limited to one or more in liquid paraffin, methyl-silicone oil, dimethicone, the vegetable oil, preferably liquid paraffin.
At prior art, bilobalide constituents in the ginkgo flavone and lactone is water insoluble, the aglycon constituents is also water insoluble in the flavone, ginkgo flavone and lactone fine powder dispersion is lower, granule can not make lactone and flavonoids effective constituent dissolving fast, influence the absorption of medicine, and then curative effect can not be as people's will, its bioavailability is on the low side simultaneously, and the inventor adopts solid dispersion technology, with Polyethylene Glycol ginkgo flavone and lactone is dissolved, suspendible, emulsifying becomes molecule or microgranule, be made into drop pill, increased surface area, improved the infiltration rate and the bioavailability of ginkgo flavone and lactone, played quick-acting and effect efficiently; The present invention adopts Macrogol 4000 and polyethylene glycol 6000 mixed-matrix as medicinal substrate, its advantage is that Polyethylene Glycol is the crystallinity water soluble (CO) polymers, the helix that two units are arranged in the per unit in the molecule, when medicine solidifies, the medicine that can comprise volume between this spiral type in the matter space, this substrate are accelerated the dissolution rate of inclusion; The molecular weight of ginkgo flavone and lactone is lower than 500, and molecular weight polyethylene glycol is 4000 and 6000, matter solid solution between the two forms; Polyethylene Glycol--behind the medicine dissolution rapidly the cooling, during low temperature the very big formation of dielectric viscosity very short hardening time, solute can form crystallite; Polyethylene Glycol is transparent in visible light and ultraviolet ray range, can directly detect with visible light or ultraviolet in assay and dissolution test.Preparation of the present invention is compared with former dosage form simultaneously, also has following advantage: effectively reduce production cost, be about 50% of former granule; Quality controllability, medicine stability, bioavailability improve greatly; But both can oral also sublingual administration, enlarged the use crowd; Active constituent content improves, and dose reduces.
The applicant has carried out a series of experiments, to prove effective effect of the present invention.
Experimental example 1: technology examination
1.1 adjuvant screening
The Polyethylene Glycol of different model is put in the small beaker, be heated to 90-100 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stir evenly, be transferred in the reservoir, the dropping liquid valve is regulated in 80 ℃ of insulations, splash in 5-10 ℃ the liquid paraffin screening of writing out a prescription with indexs such as the flowability of fusion medicinal liquid, drop pill mouldabilities.The results are shown in Table 1.
The screening of table 1 adjuvant
Prescription | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 | Prescription 6 | Prescription 7 | Prescription 8 |
Ginkgo flavone and lactone (g) | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 |
PEG4000(g) | 9 | - | 4.5 | 6 | 6.75 | 7.2 | 7.5 | - |
PEG6000(g) | - | 9 | 4.5 | 3 | 2.25 | 1.8 | 1.5 | - |
PEG8000(g) | - | - | - | - | - | - | - | 9 |
The flowability of medicinal liquid | Poor slightly | Relatively poor | Relatively poor | Good | Good | Good | Poor slightly | Good slightly |
The drop pill molded appearance | ± | ± | ± | + | + | + | ± | ± |
Drop pill hardness | Hard slightly | Hard slightly | Harder | Better | Moderate | Better | Harder | Better |
Annotate: "+" expression is dripped system smoothly, and molding is good, and pill shaped circle is whole;
" ± " expression system of dripping smoothly, but part rounding not.
The result shows: select for use PEG4000, PEG6000, PEG8000 can both satisfy the preparation requirement substantially, wherein with PEG4000: PEG6000=2: 1-4: 1 for well, PEG4000: PEG6000=3: 1 fusion medicinal liquid good fluidity, drop pill good moldability, smooth, mellow and full, so optimizing prescriptions 5.
1.2 the investigation of fusion fluid temperature and drop pill condensation temperature
In 3 batches of drop pill of prescription ratio preparation, the temperature of fusion medicinal liquid is respectively 70-75 ℃, 80-85 ℃, 85-90 ℃, and condensation temperature is respectively 2-5 ℃, 5-10 ℃, 10-15 ℃, the results are shown in Table 2.
The investigation of table 2 fusion fluid temperature and drop pill condensation temperature
Batch | 1 | 2 | 3 |
Ginkgo flavone and lactone (g) | 8 | 8 | 8 |
PEG4000(g) | 27 | 27 | 27 |
PEG6000(g) | 9 | 9 | 9 |
Fluid temperature ℃ | 70-75℃ | 80-85℃ | 85-90℃ |
Drop pill condensation temperature ℃ | 2-5℃ | 5-10℃ | 10-15℃ |
Mean droplet speed (drip/min) | 30 | 50 | 80 |
Average particle heavy (mg) | 47 | 44 | 42 |
Fusion medicinal liquid flowability | Better | Good | Better |
Outward appearance | Owe mellow and full individually | Smooth, mellow and full | Smooth, mellow and full |
Ginkgo flavone and lactone amount (mg/ grain) | 8.5 | 8 | 7.6 |
Must measure (grain) | 919 | 934 | 945 |
Yield (%) | 91.9 | 93.4 | 94.5 |
The result shows: the fusion fluid temperature is 70~90 ℃, and the drop pill condensation temperature is 2~15 ℃, all can satisfy the preparation requirement.But experimentation shows that the fusion fluid temperature is 70~75 ℃, and indivedual drop pill were not mellow and full when the drop pill condensation temperature was 2~5 ℃; The fusion fluid temperature is 85~90 ℃, and content was lower when the drop pill condensation temperature was 10~15 ℃; The fusion fluid temperature is 80-85 ℃ and drop pill condensation temperature when being 5-10 ℃, and the outward appearance of drop pill, the content of ginkgo flavone and lactone, the equal no significant difference of yield are so determine that this condition is an optimum condition.
1.3 the investigation of water dropper bore
Under above-mentioned preferred condition, compared the water dropper in 2.5mm/3.5mm, 3mm/4mm and 3.5mm/4.5mm aperture, the results are shown in Table 3.
The investigation in table 3 water dropper aperture
The aperture | 2.5mm/3.5mm | 3mm/4mm | 3.5mm/4.5mm |
The ball type | The part hangover | Rounding | Part hangover or adhesion |
Table 3 shows that the aperture is that 2.5~3.5mm/3.5~4.5mm can both satisfy the preparation requirement substantially, shows but test, and selects for use the water dropper in 3mm/4mm aperture preferable.
1.4 drip apart from investigation to shaping influence
Other experimental conditions are constant, are index with the roundness of gained drop pill, investigate the influence of dripping apart to it, the results are shown in Table 4.
The investigation of table 4 distance
Drip distance | 4-6cm | 6-8cm | 8-10cm |
The ball type | Part hangover or adhesion | Rounding | Part is rounding not |
Table 4 shows, drip apart from 4~10cm and can both satisfy the preparation requirement, but best distance is 6-8cm.
In sum, the optimised process of drop pill is: Macrogol 4000, polyethylene glycol 6000 are put in the rustless steel container in 3: 1 ratio, be heated to 90-100 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, is transferred in the reservoir 80-85 ℃ of insulation, select the water dropper in 3mm/4mm aperture for use, regulate to drip apart from be 6-8cm, regulate dropping liquid valve (speed is about 50 of per minutes), splash in 5-10 ℃ the liquid paraffin, with the drop pill drop that forms to the greatest extent and the erasing liquor paraffin body, promptly.
Concrete embodiment
Embodiment 1: ginkgo flavone and lactone 8g, Macrogol 4000 27g, polyethylene glycol 6000 9g
Macrogol 4000, polyethylene glycol 6000 are put in the rustless steel container by recipe quantity, be heated to 90-100 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, be transferred in the reservoir, 80-85 ℃ of insulation, a system condition is: water dropper bore 3mm/4mm, dripping distance is 6-8cm, regulate dropping liquid valve (drip speed and be about 50 of per minutes), splash in 5-10 ℃ the liquid paraffin, to the greatest extent and the erasing liquor paraffin body the drop pill drop that forms, make 1000 of drop pill, promptly.
Embodiment 2: ginkgo flavone and lactone 2g, Macrogol 4000 18.4g, polyethylene glycol 6000 4.6g
Macrogol 4000, polyethylene glycol 6000 are put in the rustless steel container by recipe quantity, be heated to 80-90 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, be transferred in the reservoir, 70-80 ℃ of insulation, a system condition is: water dropper bore 3.5mm/4.5mm, dripping distance is 6-8cm, regulate dropping liquid valve (drip speed and be about 50 of per minutes), splash in 5-10 ℃ the methyl-silicone oil, to the greatest extent and wipe methyl-silicone oil the drop pill drop that forms, collect drop pill, promptly.
Embodiment 3: ginkgo flavone and lactone 5g, Macrogol 4000 10g, polyethylene glycol 6000 5g
Macrogol 4000, polyethylene glycol 6000 are put in the rustless steel container by recipe quantity, be heated to 100-110 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, be transferred in the reservoir, 85-90 ℃ of insulation, a system condition is: water dropper bore 3mm/4mm, dripping distance is 4-6cm, regulate dropping liquid valve (drip speed and be about 50 of per minutes), splash in 5-10 ℃ the dimethicone, to the greatest extent and wipe dimethicone the drop pill drop that forms, collect drop pill, promptly.
Embodiment 4: ginkgo flavone and lactone 7.5g, Macrogol 4000 42.5g
Macrogol 4000 is put in the rustless steel container by recipe quantity, be heated to 80-90 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, is transferred in the reservoir 70-80 ℃ of insulation, dripping the system condition is: water dropper bore 3.5mm/4.5mm, drip apart from being 8-10cm, regulate dropping liquid valve (drip speed and be about 50 of per minutes), regulate the dropping liquid valve, splash in 2-5 ℃ the liquid paraffin, collect drop pill, promptly with the drop pill drop that forms to the greatest extent and the erasing liquor paraffin body.
Embodiment 5: ginkgo flavone and lactone 8g, polyethylene glycol 6000 32g
Polyethylene glycol 6000 is put in the rustless steel container by recipe quantity, be heated to 80~90 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, be transferred in the reservoir, 70~80 ℃ of insulations, a system condition is: water dropper bore 2.5mm/3.5mm, dripping distance is 4~6cm, regulate the dropping liquid valve, splash in 10~15 ℃ the soybean oil, to the greatest extent and wipe soybean oil the drop pill drop that forms, collect drop pill, promptly.
Embodiment 6: ginkgo flavone and lactone 6.6g, Macrogol 4000 25.05g, polyethylene glycol 6000 8.35g
Macrogol 4000, polyethylene glycol 6000 are put in the rustless steel container by recipe quantity, be heated to 100-110 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, be transferred in the reservoir, 85-90 ℃ of insulation, a system condition is: water dropper bore 3mm/4mm, dripping distance is 4-6cm, regulate dropping liquid valve (drip speed and be about 50 of per minutes), splash in 5-10 ℃ the dimethicone, to the greatest extent and the erasing liquor paraffin body the drop pill drop that forms, collect drop pill, promptly.
Embodiment 7: ginkgo flavone and lactone 8g, Polyethylene Glycol 8000 36g
Polyethylene Glycol 8000 is put in the rustless steel container by recipe quantity, be heated to 90-100 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, be transferred in the reservoir, 80-85 ℃ of insulation, a system condition is: water dropper bore 3mm/4mm, dripping distance is 6-8cm, regulate dropping liquid valve (drip speed and be about 50 of per minutes), splash in 5-10 ℃ the vegetable oil, to the greatest extent and wipe vegetable oil the drop pill drop that forms, collect drop pill, promptly.
Embodiment 8: ginkgo flavone and lactone 8g, Macrogol 4000 27g, Polyethylene Glycol 8000 9g
With Macrogol 4000, Polyethylene Glycol 8000 is put in the rustless steel container by recipe quantity, is heated to 90-100 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, is transferred in the reservoir, 80-85 ℃ of insulation, dripping the system condition is: water dropper bore 3mm/4mm, drip apart from being 6-8cm, and regulate dropping liquid valve (drip speed and be about 50 of per minutes), splash in 5-10 ℃ the liquid paraffin, collect drop pill, promptly with the drop pill drop that forms to the greatest extent and the erasing liquor paraffin body.
Embodiment 9: ginkgo flavone and lactone 8g, polyethylene glycol 6000 27g, Polyethylene Glycol 8000 9g
Polyethylene glycol 6000, Polyethylene Glycol 8000 are put in the rustless steel container by recipe quantity, be heated to 90-100 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, be transferred in the reservoir, 80-85 ℃ of insulation, a system condition is: water dropper bore 3mm/4mm, dripping distance is 6-8cm, regulate dropping liquid valve (drip speed and be about 50 of per minutes), splash in 5-10 ℃ the liquid paraffin, to the greatest extent and the erasing liquor paraffin body the drop pill drop that forms, collect drop pill, promptly.
Claims (12)
1, a kind of bilobanone ester dropping pills that is used for the treatment of cardiovascular and cerebrovascular disease, it is characterized in that, calculate according to percentage by weight, it mainly is made by ginkgo flavone and lactone 8-25%, medicinal substrate 92-75%, and described medicinal substrate is one or more mixture of Macrogol 4000, polyethylene glycol 6000, Polyethylene Glycol 8000.
2, a kind of bilobanone ester dropping pills that is used for the treatment of cardiovascular and cerebrovascular disease according to claim 1, it is characterized in that, calculate according to percentage by weight, it mainly is made by ginkgo flavone and lactone 15-20%, medicinal substrate 85-80%, and described drug matrices is the mixture of Macrogol 4000 and polyethylene glycol 6000.
3, a kind of bilobanone ester dropping pills that is used for the treatment of cardiovascular and cerebrovascular disease according to claim 1, it is characterized in that: ginkgo flavone and lactone can be commercially available or adopt conventional method to prepare, wherein the content of Ginkgo total flavones must not be lower than 44%, and the content of Ginkgo total lactones must not be lower than 6.0%.
4, a kind of bilobanone ester dropping pills that is used for the treatment of cardiovascular and cerebrovascular disease according to claim 1 and 2, it is characterized in that: the part by weight scope is 2 in the mixed-matrix of Macrogol 4000 and polyethylene glycol 6000: 1-4: 1.
5, a kind of bilobanone ester dropping pills that is used for the treatment of cardiovascular and cerebrovascular disease according to claim 4, it is characterized in that: the part by weight scope is 3: 1 in the mixed-matrix of Macrogol 4000 and polyethylene glycol 6000.
6, according to claim 1,2,3,4, any described a kind of preparation method that is used for the treatment of the bilobanone ester dropping pills of cardiovascular and cerebrovascular disease in 5, it is characterized in that, this drop pill is like this preparation: Macrogol 4000 just, polyethylene glycol 6000 and/or Polyethylene Glycol 8000 are put in the rustless steel container, be heated to 80-110 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, be transferred in the reservoir, 70-90 ℃ of insulation, dripping the system condition is: water dropper bore 2.5-3.5mm/3.5-4.5mm, drip apart from being 4-10cm, regulate the dropping liquid valve and make a speed be about 50 of per minutes, regulate the dropping liquid valve, splash in 2-15 ℃ the liquid coolant, liquid coolant is use up and wiped to the drop pill drop that forms, collect drop pill, promptly.
7, a kind of preparation method that is used for the treatment of the bilobanone ester dropping pills of cardiovascular and cerebrovascular disease according to claim 6, it is characterized in that, this drop pill is preparation like this: with Macrogol 4000, polyethylene glycol 6000 is in 2: 1-4: 1 ratio is put in the rustless steel container, be heated to 90-100 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, be transferred in the reservoir, 80-85 ℃ of insulation, a system condition is: water dropper bore 3mm/4mm, dripping distance is 6-8cm, regulate dropping liquid valve (drip speed and be about 50 of per minutes), splash in 5-10 ℃ the liquid coolant, to the greatest extent and wipe liquid coolant the drop pill drop that forms, collect drop pill, promptly.
8, according to claim 6,7 described a kind of preparation methoies that are used for the treatment of the bilobanone ester dropping pills of cardiovascular and cerebrovascular disease, it is characterized in that, this drop pill is preparation like this: with Macrogol 4000, polyethylene glycol 6000 is put in the rustless steel container in 3: 1 ratio, be heated to 90-100 ℃, treat to add the ginkgo flavone and lactone fine powder after whole fusions, stirring makes evenly, be transferred in the reservoir, 80-85 ℃ of insulation, a system condition is: water dropper bore 3mm/4mm, dripping distance is 6-8cm, regulate dropping liquid valve (drip speed and be about 50 of per minutes), splash in 5-10 ℃ the liquid coolant, to the greatest extent and wipe liquid coolant the drop pill drop that forms, collect drop pill, promptly.
9, according to claim 7 or 8 described a kind of preparation methoies that are used for the treatment of the bilobanone ester dropping pills of cardiovascular and cerebrovascular disease, it is characterized in that described liquid coolant includes but not limited to liquid paraffin, methyl-silicone oil, dimethicone, plant wet goods.
10, a kind of preparation method that is used for the treatment of the bilobanone ester dropping pills of cardiovascular and cerebrovascular disease according to claim 9 is characterized in that described liquid coolant is meant liquid paraffin.
11, a kind of preparation method that is used for the treatment of the bilobanone ester dropping pills of cardiovascular and cerebrovascular disease according to claim 6 is characterized in that, described liquid coolant includes but not limited to liquid paraffin, methyl-silicone oil, dimethicone, plant wet goods.
12, a kind of preparation method that is used for the treatment of the bilobanone ester dropping pills of cardiovascular and cerebrovascular disease according to claim 11 is characterized in that described liquid coolant is meant liquid paraffin.
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Cited By (4)
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CN101879194A (en) * | 2010-07-02 | 2010-11-10 | 山西千汇药业有限公司 | Method for preparing bilobanone ester dropping pills |
CN104997742A (en) * | 2015-07-01 | 2015-10-28 | 北京汉典制药有限公司 | Ginkgo ketonic ester dripping pill and preparation method thereof |
CN112823790A (en) * | 2019-11-21 | 2021-05-21 | 成都百裕制药股份有限公司 | A ginkgolide dripping pill and its preparation method |
CN113133976A (en) * | 2020-01-19 | 2021-07-20 | 成都百裕制药股份有限公司 | A dripping pill containing ginkgolide as effective component |
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2006
- 2006-09-28 CN CN 200610113450 patent/CN1931160A/en active Pending
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
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CN101879194A (en) * | 2010-07-02 | 2010-11-10 | 山西千汇药业有限公司 | Method for preparing bilobanone ester dropping pills |
CN104997742A (en) * | 2015-07-01 | 2015-10-28 | 北京汉典制药有限公司 | Ginkgo ketonic ester dripping pill and preparation method thereof |
CN104997742B (en) * | 2015-07-01 | 2018-05-29 | 北京汉典制药有限公司 | Bilobanone ester dropping pills and preparation method thereof |
CN112823790A (en) * | 2019-11-21 | 2021-05-21 | 成都百裕制药股份有限公司 | A ginkgolide dripping pill and its preparation method |
CN112823790B (en) * | 2019-11-21 | 2022-07-05 | 成都百裕制药股份有限公司 | A ginkgolide dripping pill and its preparation method |
CN113133976A (en) * | 2020-01-19 | 2021-07-20 | 成都百裕制药股份有限公司 | A dripping pill containing ginkgolide as effective component |
CN113133976B (en) * | 2020-01-19 | 2022-03-04 | 成都百裕制药股份有限公司 | A dripping pill containing ginkgolide as effective component |
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