CN100336516C - Ginkgo leaf extract and dipyridamole compound medicine and its preparing method - Google Patents
Ginkgo leaf extract and dipyridamole compound medicine and its preparing method Download PDFInfo
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- CN100336516C CN100336516C CNB2005100030968A CN200510003096A CN100336516C CN 100336516 C CN100336516 C CN 100336516C CN B2005100030968 A CNB2005100030968 A CN B2005100030968A CN 200510003096 A CN200510003096 A CN 200510003096A CN 100336516 C CN100336516 C CN 100336516C
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Abstract
The present invention relates to a compound drug of ginkgo biloba extract and dipyridamole and a preparation method thereof. The compound drug is prepared from ginkgo biloba extract and dipyridamole. The product has the functions of dilating the vessel, preventing arterial sclerosis, etc. and also has better treatment effect on the aspects of improving memory, treating vertigo, tinnitus and cerebrovascular diseases, etc. Compared with the prior art, the preparation of the present invention has the advantages of easily-controlled production quality, good quality stability of the product, long storage life, safe clinical use, especially convenient administration and transportation, portability, etc.
Description
Technical field: the present invention relates to the compound medicine and the preparation method of a kind of Folium Ginkgo extract and dipyridamole, belong to the technical field of medicine.
Background technology: the most important effective ingredient of Folium Ginkgo is bilobalide and flavonol, bilobalide has the effect of opposing platelet activating factor, can improve blood circulation, flavonol then has the function of eliminating free radical, except the effect that blood vessel dilating is arranged, also can prevent arteriosclerosis, Folium Ginkgo extract is improving memory, and treatment is revolved aspects such as dizzy, tinnitus and cerebrovascular disease and also had effect preferably.But oral Folium Ginkgo extract mostly is the single medicinal material preparation at present, is difficult to better bring into play the effect of symptomatic treatment.Commercially available Folium Ginkgo extract and dipyridamole formulation are the used for intravenous injection injection, have to critical patient treatment in time, act ons fast characteristics, but need medication in hospital, and the treatment of cardio-cerebralvascular chronic disease is had its deficiency, patient's medication inconvenience.
Summary of the invention: the objective of the invention is to: the compound medicine and the preparation method of a kind of Folium Ginkgo extract and dipyridamole are provided, and this drug quality good stability, safe and effective, taking convenience are to overcome the deficiency that existing medicine for treatment exists.
The present invention constitutes like this: calculate according to components by weight percent, it is prepared from by Folium Ginkgo extract 7～160 and dipyridamole 0.7～16.Specifically: the weight ratio of Folium Ginkgo extract and dipyridamole is between 5: 1 to 20: 1, and it is optimized than being 10: 1.
The preparation method of the compound medicine of described Folium Ginkgo extract and dipyridamole: it may further comprise the steps:
A), get Folium Ginkgo, pulverize, the alcohol heating reflux that adds consumption respectively and be 12 times～6 times water of primary dose or 1%～80% extracts 1～3 time, each 1～3 hour, merge extractive liquid,, decompression recycling ethanol, be concentrated into an amount of after, with 1～3 times amount of concentrated solution thin up to primary dose, under 5～40 ℃, left standstill 4～24 hours, filter, get the macroporous adsorptive resins of supernatant, discard effluent by having handled, cylinder absorption reach saturated after, water or 1%～30% ethanol with 1～5 times of cylinder are washed post, and 40%～95% ethanol elution is collected eluent, surveying relative density during decompression recycling ethanol to 50 ℃ is the extractum of 1.05-1.25, at 40 ℃～80 ℃ following vacuum dryings, pulverize, get the Folium Ginkgo extract crude product;
B), above-mentioned Folium Ginkgo extract crude product is added the heating of 20% ethanol and make it dissolving, liquor strength is about 5%, placed 4～12 hours 5～40 ℃ of coolings, filter the anion exchange resin of filtrate by having handled, collect effluent, and, merging effluent and eluent with the ethanol elution of 1～5 times of column volume 10%～30%, surveying relative density when being evaporated to 50 ℃ is 1.05～1.25, at 40 ℃～80 ℃ following vacuum dryings, get Folium Ginkgo extract;
C), get Folium Ginkgo extract 7～160g and dipyridamole 0.7～16g, be ground into fine powder, cross 100 mesh sieves, promptly obtain active component of the present invention, the active component that obtains is prepared into oral formulations according to conventional method, comprising: drop pill, capsule, tablet.
Specifically: it may further comprise the steps:
A), get Folium Ginkgo, pulverize, adding consumption respectively is 10 times of primary doses, 8 times 60% alcohol heating reflux extracts 2 times, each 2 hours, merge extractive liquid,, decompression recycling ethanol, be concentrated into an amount of after, with the 2 times amounts of concentrated solution thin up to primary dose, under 5～10 ℃, left standstill 24 hours, filter, get the DA201 type macroporous adsorptive resins of supernatant, discard effluent by having handled, cylinder absorption reach saturated after, water and 10% ethanol with 3 times of cylinders are washed post, and 70% ethanol elution is collected eluent, surveying relative density during decompression recycling ethanol to 50 ℃ is the extractum of 1.10-1.15, at 60 ℃ of following vacuum dryings, pulverize, get the Folium Ginkgo extract crude product;
B), above-mentioned Folium Ginkgo extract crude product is added the heating of 20% ethanol and make it dissolving, liquor strength is 5%, place 5～10 ℃ of coolings, filter the 717 type strong-base anion-exchange resins of filtrate by having handled, collect effluent, and, merging effluent and eluent with the ethanol elution of 3 times of column volumes 20%, surveying relative density when being evaporated to 50 ℃ is 1.10～1.15, at 60 ℃ of vacuum dryings, get Folium Ginkgo extract;
C), get Folium Ginkgo extract 14.0g, dipyridamole 1.4g is ground into fine powder, cross 100 mesh sieves, mixing adds 10.3g Macrogol 4000,20.5g polyethylene glycol 6000,70～80 ℃ of fusions, stir, spice is incubated the system of dripping down at 70～80 ℃, and by 5～10 ℃ of simethicone cooling columns, drop removes coolant, make drop pill 1000 balls, promptly get dropping pill formulation.
Among the present invention; get Folium Ginkgo extract 40g, dipyridamole 4g is ground into fine powder; cross 100 mesh sieves; added lactose 80g, microcrystalline Cellulose 40g, starch 50g, micropowder silica gel 30g, the carboxymethyl starch 10g of 100 mesh sieves, mixing, the starch slurry with 1～5% are wetting agent; in a step comminutor, granulate; add 5～20g magnesium stearate, tabletting, extension film-coat, make 1000, promptly get tablet.
Among the present invention, get Folium Ginkgo extract 80g, dipyridamole 8g is ground into fine powder, crosses 100 mesh sieves, adds starch 120g, lactose 40g, micropowder silica gel 6g, mix homogeneously, and the fill capsule makes 1000 of capsules, promptly gets capsule preparations.
The present invention compared with prior art, its quality of production is controlled easily, product quality stability is good, long shelf-life, and is clinical safe in utilization, and takes, transports, carries advantages such as especially convenient.
Pharmacological evaluation:
1, material and method: medicine and reagent: be subjected to test product: Ginkgodamo drip pill raw material, yellow powder, lot number: 031101.Positive control drug, Ginkgo Leaf Extract and Dipyridamole Injection, lot number 20040103, Guizhou Yibai Pharmaceutical Co., Ltd's product.Positive control drug, FUFANG DANSHEN DIWAN, lot number 20031014, Tianjin Tasly Pharmaceutical Co., Ltd's product.Lignocaine, lot number 20030708, Beijing Yimin Pharmaceutical Co., Ltd. produces; Pentobarbital sodium, lot number 020919, the import packing of Beijing chemical reagents corporation; Red tetrazolium (TTC), lot number 1412B41, AMRESCO company product; Heparin sodium injection, lot number 030628, Chinese changzhou biochemical thousand red pharmaceutical Co. Ltds produce.Animal: the hybrid dog, the male and female dual-purpose, body weight: 17.5 ± 2.2kg, the first edge laboratory animal of virtue plant provides by Beijing.Instrument: SC-3 type electric pulmotor (Shanghai Medical Equipment Factory); MFV-3200 type electromagnetic flowmeter (Japanese photoelectricity product); MP150 type physiograph (U.S. BIOPAC company); RMP6008 physiograph (Japanese photoelectricity product); R80 type blood viscosity instrument (Beijing Steellex Scientific Instrument Company).Dosage grouping and administration: positive control drug Ginkgo Leaf Extract and Dipyridamole Injection, every 5ml contain Semen Ginkgo total flavones 4.5～5.5mg, contain dipyridamole 1.8～2.2mg, the each 10～25ml of adult's intravenous drip, twice of every day.With maximal dose conversion every day, then dog dosage is 1.2ml/kg.Experiment medium-sized vein drug administration by injection, control are injected speed and are finished in 10 minutes.The positive control drug FUFANG DANSHEN DIWAN, oral or sublingual administration, each 10 balls (the heavy 27mg of every ball) convert with this dosage every day 3 times, and dog dosage is 21mg/kg, duodenal administration in the test.Convert according to Ginkgo Leaf Extract and Dipyridamole Injection dosage, two kinds of effective ingredient people consumptions are respectively: about 50mg/ day of Ginkgo total flavones, dipyridamole 20mg/ day, contain the ratio reckoning of total flavones 1mg in addition according to every 4mg Semen Ginkgo extrac, people's consumption every day is Semen Ginkgo extrac 200mg, dipyridamole 20mg is so former dosage form dosage ratio is 10: 1.The reagent that is subjected to of considering this research is a drops, bioavailability is low than injection, regulation Folium Ginkgo extract human dosage is 80mg/ time in the pharmacopeia in addition, every day three times, be 240mg/ day, thus determine in the test with Folium Ginkgo extract 240mg/ day be middle dosage, simultaneously with reference to 10: 1 ratio of former dosage form, determine that dosage is 24mg/ day in the dipyridamole, it is 6.4mg/kg: 0.64mg/kg (in: in) that this dosage is converted to dog.For verifying the science of 10: 1 proportionings of two kinds of effective ingredient, in the test except that carrying out height: high, in: in, low: low three groups, also carried out height: middle and high: low, in: high and low: high and low: in, in: the low dose compatibility that waits is tested, result to each dose compatibility analyzes, to obtain two best component ratios.Each dose compatibility sample is provided by Guizhou Yibai Pharmaceutical Co., Ltd, is made into suitable solution, duodenal administration with preceding with distilled water.Step: animal is divided into 12 groups at random, is provided with as described above.Pentobarbital sodium 30mg/kg intravenous injection anesthesia separates left carotid, and intubate connects the pressure transducer recording blood pressure.Tracheal intubation is carried out assisted respiartion.The 4th intercostal is opened breast along the left side, seam pericardium bed.Separate aortic arch, place the electromagnetic flowmeter probe, measure cardiac output.Apex of the heart intubate connects pressure transducer, measures intraventricular pressure.Seam is put 16 epicardial leads of leading and is connected ecg amplifier, record visceral pericardium electrocardiogram.The abdominal part opening separates duodenum and is equipped with administrable.After every index that writes down is stablized 15min, adopt two steps ligation method ligation arteria coronaria left anterior descending branch, and administration in 15 minutes after formal ligation, model group is given the normal saline with the capacity of grade.Respectively before ligation, ligation at once, 5,10,15,30,45,60,90,120,150,180min record visceral pericardium electrocardiogram.Respectively at 180min time point heart extracting blood before the pre-bundle and after the ligation, measure whole blood viscosity.It is dirty to core during off-test, on average is cut into five from the apex of the heart to ligation point, and 1%TTC dyeing is taken pictures, and picture is imported computer, calculates the ratio of infarct size and cutting cardiac muscular tissue area.Observation index: myocardial ischemia experiment: degree of myocardial ischemia (each each mapping point ST section of the moment is raised total millivolt of number), myocardial ischemia scope (each moment ST section is raised greater than the mapping of 2mV and counted), the myocardial infarction coloration result, the ratio of cutting cardiac muscular tissue area (infarct size with), whole blood viscosity: in testing front and back at shear rate 1,50,100, measure whole blood viscosity 200 times, hemodynamics experiment: before experiment, after the ligation 30,60,120,180 minutes (is after the administration 15,45,105,165 minutes) observe: systolic arterial pressure (BPmax), auterial diastole is pressed (BPmin), tremulous pulse mean pressure (BPmean), left side chamber EDP (LVEDP), left indoor pressure rising maximal rate (dp/dtmax), cardiac output (CO), the acting of chamber, a left side (LVW=CO * (Pmean-LVEDP)), myocardial oxygen consumption (tension time index, TTI=heart rate * left ventricular ejection phase area).
2, result: Semen Ginkgo: dipyridamole 12.8: 1.28,6.4: 0.64,3.2: 0.32mg/kg shows tangible function of resisting myocardial ischemia, dwindles myocardial ischemia area, alleviate myocardial ischemia degree, dwindles the myocardial infarction area that cardiac muscle dyeing shows.
● Folium Ginkgo extract: dipyridamole 3.2: 0.64mg/kg has certain trend aspect myocardial ischemia area, the alleviate myocardial ischemia degree dwindling, and obviously dwindles the myocardial infarction area that cardiac muscle dyeing shows simultaneously.
● Folium Ginkgo extract: dipyridamole 12.8: 1.28,6.4: 0.64,3.2: the 0.32mg/kg drug effect obviously is better than the injection matched group, compares with Radix Salviae Miltiorrhizae drop pill, and above-mentioned each administration group drug effect is the regular hour dependency.
● heart inhibitory action such as tangible blood pressure drops, decreased heart rate, myocardium shrinkage function reduction appear in animal after the administration of ginkgo bilobate extract injection.
● Folium Ginkgo extract: animal blood pressure obviously rises after dipyridamole 12.8mg/kg: 1.28mg/kg group and the administration of 6.4mg/kg: 0.64mg/kg group.
3, conclusion: Folium Ginkgo extract: dipyridamole 12.8mg/kg: 1.28mg/kg group, 6.4mg/kg: 0.64mg/kg group and 3.2mg/kg: 0.32mg/kg group have myocardial ischemia effect due to the tangible anti-dog coronary ligation, its action intensity is better than other dosage ratio group, is better than the effect of Ginkgo Leaf Extract and Dipyridamole Injection simultaneously.
Toxicity (the acute and long term toxicity test brief summary of this product):
This product mouse stomach acute toxicity test LD50 6480.1mg/kg.This product rat oral gavage is not measured LD50 and is not seen the tangible toxic action of rat.This product rat oral gavage 100,316,1000mg/kg administration 3 months under maximal dose administration concentration condition, is not seen the tangible toxic action of rat.
Illustrate that this product oral administration does not have the overt toxicity effect.
This product drop pill technical study:
(1) proportioning of medicine and substrate: find out that through test different dripping of drop pill made the very big wherein more selectable ratio of type influence is medicine: substrate (1: 1.5-1: 2) for the proportioning of medicine and substrate.
The proportioning of table 1. medicine and substrate
| Medicine: substrate | The fusion situation | Stickiness | Drip the system situation |
| 1∶1.0 1∶1.5 1∶2.0 1∶2.5 | Be difficult for fusion and easily fuse the meltable easy fusion of closing | Sticky moderate | The difficult system of dripping is better dripped the system of dripping that makes of dripping that makes |
(2) medicine and substrate composition and drop temperature are selected: with the kind of substrate, and the proportioning of medicine and substrate, dripping system temperature and coolant temperature is A, B, C, D four factors, makes L
9(3
4) orthogonal optimum seeking test, design and the results are shown in Table 5,6,7.Fixed controlled condition: water dropper internal diameter 3.0mm, external diameter 4.0mm, water dropper is apart from cooling liquid level 8cm.Cooling column height 60cm.
Table 2 factor level table
| Factor level | The A matrix species | B medicine: substrate (g: g) | C drop temperature (℃) | The D coolant temperature (℃) |
| 1 2 3 | Macrogol 4000: polyethylene glycol 6000, (1: 1) polyethylene glycol 6000 Macrogol 4000: polyethylene glycol 6000, (1: 2) | 1.0∶2.0 1.0∶1.7 1.0∶1.5 | 70 80 90 | 5 10 15 |
Table 3 medicine and substrate composition, a system temperature are selected test and result
| Tested number | The A matrix species | B medicine: substrate (g: g) | C drip the system temperature (℃) | The D chilling temperature (℃) | RSD (%) as a result |
| 1 2 3 4 5 6 7 8 | 1 1 1 2 2 2 3 3 | 1 2 3 1 2 3 1 2 | 1 2 3 2 3 1 3 1 | 1 2 3 3 1 2 2 3 | 2.97 2.67 3.67 2.31 3.24 3.93 1.94 2.61 |
| 9 K 1 K 2 K 3 R | 3 9.31 9.48 6.63 2.85 | 3 7.22 8.52 9.68 2.46 | 2 9.51 7.06 8.85 2.45 | 1 8.29 8.54 8.59 0.30 | 2.08 |
Table 4 test variance analysis
| Soruces of variation | Sum of deviation square | Degree of freedom | Mean square | The F value | Significance |
| A B C error | 1.704 1.010 1.071 0.017 | 2 2 2 | 0.852 0.505 0.536 0.0085 | 100 59 63 | P＜0.01 ** P＜0.05 * P＜0.05 * |
Conclusion: find out that from extreme difference R value A, B, C three factors are all influential, the D factor affecting is little.Find out that from The results of analysis of variance the A factor is very remarkable, P＜0.01, B, C two factors are also remarkable, P＜0.05.The drop pill optimum process condition: substrate is Macrogol 4000: polyethylene glycol 6000 (1: 2); Medicine: substrate (g:, also can reach good effect at 1.0: 1.7 o'clock g) with 1.0: 2.0 the bests; The spice heat-retaining condition is best with 80 ℃; But 5 ℃-10 ℃ of chilling temperatures are the drop pill cooling forming all the time, with 5 ℃ of the bests.
This product capsule technical study:
Hard capsule is when preparation medicated powder, because the physical property difference of ingredient is dealt with the granularity inequality of medicated powder, layering when easily causing fill, mobile bad phenomenon improperly when adjuvant uses.By to capsule filler starch, lactose and fluidizer micropowder silica gel proportioning test, the results are shown in Table.
Table 5 capsule adjuvant is to EFFECT OF CORK STOPPER
| Composition proportion | Medicated powder (g) | Starch (g) | Lactose (g) | Disintegration (branch) as a result |
| 1 2 3 | 44 44 44 | 120 80 40 | 40 80 120 | 15 18 25 |
Table 6 capsule adjuvant is to the influence of medicated powder flowability
| Composition proportion | Medicated powder (g) | Starch (g) | Lactose (g) | Micropowder silica gel (g) | Medicated powder flowability as a result |
| 1 2 3 | 44 44 44 | 120 120 120 | 40 40 40 | 2 6 10 | Carefully relatively poor |
*In 1000 seed lac wafer consumptions
Find out starch from result of the test: lactose (120g: 40g) add micropowder silica gel 3% (6g) medicated powder flowability better for well disintegration.
This product tablet technical study:
This product is a thin membrane coated tablet, has good disintegration simultaneously at the sheet heart, also certain rigidity should be arranged, and just can carry out the coating operation.Compared starch, the lactose consumption consumption of sodium carboxymethyl cellulose when by experiment, to the disintegration of the sheet heart and the influence of hardness, testing program is the A factor with lactose and starch proportioning, is the B factor with the addition of carboxymethyl cellulose, carries out L
4(2
3) test, the results are shown in Table.
Table 7 film-making agent adjuvant factor level table
| Factor level | A lactose: little product cellulose: starch: micropowder silica gel (g) | B sodium carboxymethyl cellulose addition (g) |
| 1 2 | 80∶40∶50∶30 60∶40∶70∶30 | 10 5 |
*In 1000 tablet dosages.
Table 7 film-making and test technology scheme and result
| Tested number | A | B | C (sky) | The result | |
| Disintegration (minute) | Sheet hardness (kg) | ||||
| 1234 disintegration K1 | 1 1 2 2 55 | 1 2 1 2 42 | 1 2 2 1 45 | 15 40 27 30 | 8.5 7.2 6.5 6.0 |
| The hard-hearted degree of K2 R sheet K1 K2 R | 57 3 15.7 12.5 3.2 | 70 28 15.0 13.2 2.8 | 67 22 14.5 13.7 0.8 |
Conclusion: from test extreme difference R value result, the B factor is good with B1 to influence disintegration greatly, when promptly making 1000, the sodium carboxymethyl cellulose dosage with 10g for well; A, B two factors are all influential to the hardness of sheet, A1＞A2, B1＞B2, when promptly making 1000, lactose: microcrystalline Cellulose: starch: micropowder silica gel (80g: 40g: 50g: 30g) optimum, sodium carboxymethyl cellulose dosage with 10g for well.
The specific embodiment:
Embodiments of the invention 1 (tablet): get Folium Ginkgo, pulverize, adding consumption respectively is 10 times of primary doses, 8 times 60% alcohol heating reflux extracts 2 times, each 2 hours, merge extractive liquid,, decompression recycling ethanol, be concentrated into an amount of after, with the 2 times amounts of concentrated solution thin up to primary dose, under 5～10 ℃, left standstill 24 hours, filter, get the DA201 type macroporous adsorptive resins of supernatant, discard effluent by having handled, cylinder absorption reach saturated after, water and 10% ethanol with 3 times of cylinders are washed post, and 70% ethanol elution is collected eluent, surveying relative density during decompression recycling ethanol to 50 ℃ is the extractum of 1.10-1.15, at 60 ℃ of following vacuum dryings, pulverize, get the Folium Ginkgo extract crude product; Above-mentioned Folium Ginkgo extract crude product is added the heating of 20% ethanol make it dissolving, liquor strength is 5%, place 5～10 ℃ of coolings, filter the 717 type strong-base anion-exchange resins of filtrate by having handled, collect effluent, and, merging effluent and eluent with the ethanol elution of 3 times of column volumes 20%, surveying relative density when being evaporated to 50 ℃ is 1.10～1.15, at 60 ℃ of vacuum dryings, get Folium Ginkgo extract; Get Folium Ginkgo extract 40g; dipyridamole 4g; be ground into fine powder, cross 100 mesh sieves, added lactose 80g, microcrystalline Cellulose 40g, starch 50g, micropowder silica gel 30g, the carboxymethyl starch 10g of 100 mesh sieves; mixing; starch slurry with 1～5% is a wetting agent, granulates in a step comminutor, adds 5～20g magnesium stearate, tabletting, extension film-coat; make 1000, promptly get tablet.
Embodiments of the invention 2 (capsule preparations): get Folium Ginkgo, pulverize, the adding consumption is that the alcohol heating reflux of 10 times 60% of primary dose extracts 1 time, each 3 hours, merge extractive liquid,, decompression recycling ethanol, be concentrated into an amount of after, with the 3 times amounts of concentrated solution thin up to primary dose, under 5～10 ℃, left standstill 24 hours, filter, get the DA201 type macroporous adsorptive resins of supernatant, discard effluent by having handled, cylinder absorption reach saturated after, water and 10% ethanol with 2 times of cylinders are washed post, and 70% ethanol elution is collected eluent, surveying relative density during decompression recycling ethanol to 50 ℃ is the extractum of 1.10-1.15, at 50 ℃ of following vacuum dryings, pulverize, get the Folium Ginkgo extract crude product; Above-mentioned Folium Ginkgo extract crude product is added the heating of 20% ethanol make it dissolving, liquor strength is 5%, place 5～10 ℃ of coolings, filter the 717 type strong-base anion-exchange resins of filtrate by having handled, collect effluent, and, merging effluent and eluent with the ethanol elution of 2 times of column volumes 20%, surveying relative density when being evaporated to 50 ℃ is 1.10～1.15, at 50 ℃ of vacuum dryings, get Folium Ginkgo extract; Get Folium Ginkgo extract 80g, dipyridamole 8g is ground into fine powder, crosses 100 mesh sieves, adds starch 120g, lactose 40g, micropowder silica gel 6g, mix homogeneously, and the fill capsule makes 1000 of capsules, promptly gets capsule preparations.
Embodiments of the invention 3 (dropping pill formulation): get Folium Ginkgo, pulverize, adding consumption respectively is 10 times of primary doses, 8 times, 6 times 60% alcohol heating reflux extracts 3 times, each 1 hour, merge extractive liquid,, decompression recycling ethanol, be concentrated into an amount of after, with the 1 times amount of concentrated solution thin up to primary dose, under 5～10 ℃, left standstill 24 hours, filter, get the DA201 type macroporous adsorptive resins of supernatant, discard effluent by having handled, cylinder absorption reach saturated after, water and 10% ethanol with 4 times of cylinders are washed post, and 70% ethanol elution is collected eluent, surveying relative density during decompression recycling ethanol to 50 ℃ is the extractum of 1.10-1.15, at 70 ℃ of following vacuum dryings, pulverize, get the Folium Ginkgo extract crude product; Above-mentioned Folium Ginkgo extract crude product is added the heating of 20% ethanol make it dissolving, liquor strength is 5%, place 5～10 ℃ of coolings, filter the 717 type strong-base anion-exchange resins of filtrate by having handled, collect effluent, and, merging effluent and eluent with the ethanol elution of 4 times of column volumes 20%, surveying relative density when being evaporated to 50 ℃ is 1.10～1.15, at 70 ℃ of vacuum dryings, get Folium Ginkgo extract; Get Folium Ginkgo extract 14.0g, dipyridamole 1.4g is ground into fine powder, cross 100 mesh sieves, mixing adds 10.3g Macrogol 4000,20.5g polyethylene glycol 6000,70～80 ℃ of fusions, stir, spice is incubated the system of dripping down at 70～80 ℃, and by 5～10 ℃ of simethicone cooling columns, drop removes coolant, make drop pill 1000 balls, promptly get dropping pill formulation.
Claims (4)
1, the compound medicine of Folium Ginkgo extract and dipyridamole calculates according to components by weight percent, and it is prepared from for 0.7～16 part by 7～160 parts of Folium Ginkgo extract and dipyridamole; It is characterized in that: it prepares like this:
A), get Folium Ginkgo, pulverize, the alcohol heating reflux that adds consumption respectively and be 12 times～6 times water of primary dose or 1%～80% extracts 1～3 time, each 1～3 hour, merge extractive liquid,, decompression recycling ethanol, be concentrated into an amount of after, with 1～3 times amount of concentrated solution thin up to primary dose, under 5～40 ℃, left standstill 4～24 hours, filter, get the macroporous adsorptive resins of supernatant, discard effluent by having handled, cylinder absorption reach saturated after, water or 1%～30% ethanol with 1～5 times of cylinder are washed post, and the ethanol elution of reuse 40%～95% is collected eluent, surveying relative density during decompression recycling ethanol to 50 ℃ is the extractum of 1.05-1.25, at 40 ℃～80 ℃ following vacuum dryings, pulverize, get the Folium Ginkgo extract crude product;
B), above-mentioned Folium Ginkgo extract crude product is added the heating of 5%～40% ethanol and make it dissolving, liquor strength is about 3%～10%, placed 4～12 hours 5～40 ℃ of coolings, filter the anion exchange resin of filtrate by having handled, collect effluent, and, merging effluent and eluent with the ethanol elution of 1～5 times of column volume 10%～30%, surveying relative density when being evaporated to 50 ℃ is 1.05～1.25, at 40 ℃～80 ℃ following vacuum dryings, get Folium Ginkgo extract;
C), get Folium Ginkgo extract 7～160g and dipyridamole 0.7～16g, be ground into fine powder, cross 100 mesh sieves, promptly obtain active component, the active component that obtains is prepared into oral formulations according to conventional method, comprising: drop pill, capsule, tablet.
2, according to the compound medicine of described Folium Ginkgo extract of claim 1 and dipyridamole, it is characterized in that: it prepares like this:
A), get Folium Ginkgo, pulverize, adding consumption respectively is 10 times of primary doses, 8 times 60% alcohol heating reflux extracts 2 times, each 2 hours, merge extractive liquid,, decompression recycling ethanol, be concentrated into an amount of after, with the 2 times amounts of concentrated solution thin up to primary dose, under 5～10 ℃, left standstill 24 hours, filter, get the DA201 type macroporous adsorptive resins of supernatant, discard effluent by having handled, cylinder absorption reach saturated after, water and 10% ethanol with 3 times of cylinders are washed post, and 70% ethanol elution is collected eluent, surveying relative density during decompression recycling ethanol to 50 ℃ is the extractum of 1.10-1.15, at 60 ℃ of following vacuum dryings, pulverize, get the Folium Ginkgo extract crude product;
B), above-mentioned Folium Ginkgo extract crude product is added the heating of 20% ethanol and make it dissolving, liquor strength is 5%, place 5～10 ℃ of coolings, filter the 717 type strong-base anion-exchange resins of filtrate by having handled, collect effluent, and, merging effluent and eluent with the ethanol elution of 3 times of column volumes 20%, surveying relative density when being evaporated to 50 ℃ is 1.10～1.15, at 60 ℃ of vacuum dryings, get Folium Ginkgo extract;
C), get Folium Ginkgo extract 7～28g, dipyridamole 0.7～2.8g is ground into fine powder, cross 100 mesh sieves, mixing adds 5～20g Macrogol 4000,10～30g polyethylene glycol 6000,50～90 ℃ of fusions, stir, spice is incubated the system of dripping down at 70～80 ℃, and by 2～30 ℃ of simethicone cooling columns, drop removes coolant, make drop pill 1000 balls, promptly get dropping pill formulation.
3, according to the compound medicine of described Folium Ginkgo extract of claim 1 and dipyridamole; it is characterized in that: get Folium Ginkgo extract 20～80g; dipyridamole 2～8g; be ground into fine powder; cross 100 mesh sieves; lactose 20～120g, the microcrystalline Cellulose 10～80g, starch 20～80g, micropowder silica gel 10～40g, the sodium carboxymethyl cellulose 5～20g that added 100 mesh sieves; mixing; starch slurry with 1%～5% is a wetting agent; in a step comminutor, granulate; add 5～20g magnesium stearate, tabletting, extension film-coat, make 1000, promptly get tablet.
4, according to the compound medicine of described Folium Ginkgo extract of claim 1 and dipyridamole, it is characterized in that: get Folium Ginkgo extract 40～160g, dipyridamole 4～16g, be ground into fine powder, cross 100 mesh sieves, add starch 60～240g, lactose 20～80g, micropowder silica gel 3～20g, mix homogeneously, the fill capsule makes 1000 of capsules, promptly gets capsule preparations.
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| CNB2005100030968A CN100336516C (en) | 2005-06-03 | 2005-06-03 | Ginkgo leaf extract and dipyridamole compound medicine and its preparing method |
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| CN100336516C true CN100336516C (en) | 2007-09-12 |
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| CN1569060A (en) * | 2003-07-25 | 2005-01-26 | 李炳阳 | Oral compound medicament with gingko leaf extractions |
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| CN1569060A (en) * | 2003-07-25 | 2005-01-26 | 李炳阳 | Oral compound medicament with gingko leaf extractions |
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| Title |
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| 银杏中有效成分的提取分离 温普红，现代中药研究与实践，第18卷第2期 2004 * |
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