CN1883472A - Orally disintegrating tablet of ginkgolide and preparation method thereof - Google Patents
Orally disintegrating tablet of ginkgolide and preparation method thereof Download PDFInfo
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- CN1883472A CN1883472A CNA2006100403737A CN200610040373A CN1883472A CN 1883472 A CN1883472 A CN 1883472A CN A2006100403737 A CNA2006100403737 A CN A2006100403737A CN 200610040373 A CN200610040373 A CN 200610040373A CN 1883472 A CN1883472 A CN 1883472A
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Abstract
The invention discloses an orally disintegrating tablet of bilobalide and its preparing process, wherein the tablet mainly comprises 1 part of bilobalide, 0.1-1 part of low substituted methylcellulose propylene glycol ether and / or sodium carboxymethylstarch and / or cross-linked sodium carboxymethylcellulose and / or crosslinked povidone, 1-10 parts of crystalline cellulose and / or mannitol bulking agent, 0.01-0.1 part of sodium dodecylsulphate surface active agent, 0.05-0.5 part of anhydrous citric acid and / or sodium hydrogen carbonate.
Description
Technical field
The present invention relates to a kind ofly astringe the lung, relieving asthma, blood circulation promoting and blood stasis dispelling, pain relieving is used for the treatment of the Orally disintegrating tablet of ginkgolide and preparation method thereof of the phlegm stagnation in collateral disease of cough and asthma due to lung deficiency, coronary heart disease, angina pectoris, hyperlipemia, (cerebral thrombosis, cerebral embolism) apoplexy apoplex involving the channels and collaterals.
Background technology
Bilobalide is to find the strongest platelet activating factor (plateletacllvatfactor at present, PAF) receptor antagonist, platelet activating factor (PAF) is a kind ofly to produce the endogenous activity material can act on various kinds of cell again by various kinds of cell, has biological action widely.In vivo, PAF participates in many pathophysiological processes, acts on widely, and activity is very big.Found that PAF plays an important role in the pathological processes such as shock that thrombosis, asthma, organ-graft refection, acute inflammation, heart allergy, endotoxin and IgG cause.At present the bilobalide peroral dosage form is mainly conventional tablet because bilobalide itself is insoluble in water, common oral tablet, then not easy disintegrating, discharge not exclusively in vivo, bioavailability is also lower.
The process for prepaing ginkgo leaf dispersion tablet that Chinese patent CN1502340A discloses, be will be from Folium Ginkgo extract (bilobalide and flavonoid mixture), adding is not less than total sheet and weighs 5%, is not more than 30%, swellbility is greater than carboxymethyl starch sodium (CMS-Na), low-substituted hydroxypropyl cellulose (LS-HPC), crospolyvinylpyrrolidone (PVPP), the cross-linking sodium carboxymethyl cellulose disintegrating agents such as (CCMC-Na) of 5ml/g, and starch, microcrystalline Cellulose etc. fill adjuvant and fluidizer tablet forming, make disintegration time less than 180 seconds dispersible tablet.But this dispersible tablet does not only reach the quick disintegrate requirement in oral cavity, and still needing medicine to arrive stomach could decompose, and can not reach quick performance drug effect, and be unfavorable for that dysphagia person takes, and is unfavorable for that patient with angina pectoris brings into play drug action fast; And principal agent is the bilobalide-containing that extracts of Folium Pruni and the mixture of ginkgetin, and institute's bilobalide-containing content is low, only about 6%, can not give full play to the distinctive drug action of bilobalide itself.And this dosage form can not absorb by Orally disintegrating, compares it with oral cavity disintegration tablet and absorbs slowly, and bioavailability is lower.
The disclosed Ginkgo biloba extract orally disintegrating tablets and the preparation method of Chinese patent CN1660222A is that the Semen Ginkgo extrac and the excipient (disintegrating agent, diluent, correctives, fluidizer) that are wrapped with the basic coated cellulose material of first (second) are pressed 1: 1～1: 3 mixed pressuring plate.Make disintegrating tablet by making the coated granule method, because the cumbersome cost height of technology, need at first make coated granule, add excipient again and make disintegrating tablet, be wrapped in the granule after principal agent is coated, can influence in the body of principal agent fast, absorb fully.What it solved only is to cover the bitterness of Folium Ginkgo extract own by coating, still because of bilobalide content is low, and does not have the above-mentioned disease effect of treatment.
Summary of the invention
The object of the present invention is to provide a kind of bilobalide content height, convenient oral, fast Absorption can improve the Orally disintegrating tablet of ginkgolide of bioavailability.
Another object of the present invention is to provide a kind of preparation method of above-mentioned Orally disintegrating tablet of ginkgolide.
Orally disintegrating tablet of ginkgolide of the present invention, it is characterized in that basically by 1 part of bilobalide, 0.1～1 part of low-substituted hydroxypropyl cellulose and/or carboxymethyl starch sodium and/or cross-linking sodium carboxymethyl cellulose and/or polyvinylpolypyrrolidone disintegrating agent, 1～10 part of microcrystalline Cellulose and/or mannitol filler, 0.01～0.1 part of sodium lauryl sulphate surfactant, 0.05～0.5 part of anhydrous citric acid and/or sodium bicarbonate are formed.
The said bilobalide of the present invention is meant the bilobalide effective site of extracting gained from Folium Ginkgo, comprises ginkalide A, ginkalide B, ginkalide C, wherein better is lactone total content 〉=70%, ginkalide B content 〉=40%.
The said filler of the present invention, preferred amounts are 1.5～3 parts.
In addition, for making things convenient for tabletting, can also add among the present invention in right amount as fluidizer such as micropowder silica gel, magnesium stearate, to improve the flowability of micro powder granule; And the medicine that adds an amount of improvement taste correctives commonly used.
Orally disintegrating tablet of ginkgolide preparation of the present invention: it is characterized in that required supplementary material is crossed 100 mesh sieves respectively, standby; Take by weighing the abundant mix homogeneously of adjuvant respectively by prescription; The bilobalide that adds recipe quantity is with the abundant mixing of above-mentioned adjuvant, compressing dry granulation.
Orally disintegrating tablet of ginkgolide of the present invention, owing to not only select in low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, the polyvinylpolypyrrolidone disintegrating agent one or more for use, but also add anhydrous citric acid and/or sodium bicarbonate disintegrating agent, thereby make the tablet of the present invention disintegrate rapidly that makes, and need in the presence of a small amount of saliva, be solvable loosing only, can reach in the oral cavity fully is the disintegratable requirement.Test shows: after the slightly solubility bilobalide was made oral cavity disintegration tablet of the present invention, sample disintegrate in 1 minute was complete, helps bringing into play rapidly the drug action of bilobalide, thereby had accelerated bilobalide rate of release in vivo.The existing bilobalide oral agents of the present invention has: rate of release is fast, taking convenience, the bioavailability height, because of can directly in the oral cavity, utilizing saliva tablet is decomposed fully, made things convenient for dysphagia (as the old people) patient, and there is not first pass effect because oral mucosa absorbs, thereby improved blood drug level and bioavailability; Compliance is good, and owing to this product can be disperseed in the oral cavity rapidly, and mouthfeel is good, and the compliance that the patient takes this product is good, can not cause bad irritant reaction.And because bilobalide content height (lactone total content 〉=70%, ginkalide B content 〉=40%), drug action is obvious.The test of pesticide effectiveness shows: Orally disintegrating tablet of ginkgolide of the present invention, can reduce the generation of cerebral infarction, and cerebral ischemia there is protective effect; and can reduce the formation of thrombosis, anticoagulant can be astringed the lung; relieving asthma; blood circulation promoting and blood stasis dispelling, pain relieving is applicable to cough and asthma due to lung deficiency; coronary heart disease; angina pectoris, hyperlipemia, the phlegm stagnation in collateral disease of treatment (cerebral thrombosis, cerebral embolism) apoplexy apoplex involving the channels and collaterals.Overcome the problem that the ordinary tablet disintegration rate is slow, release is low.(seeing pharmacodynamics test for details)
The specific embodiment
Embodiment: by the Example formulations table, supplementary material is crossed 100 mesh sieves respectively, standby.Take by weighing the abundant mix homogeneously of adjuvant respectively by prescription, add the bilobalide of recipe quantity, abundant mixing, compressing dry granulation, packing.
The Example formulations table
| Example 1 | Example 2 | Example 3 | Example 4 | Example 5 | Example 6 | Example 7 | Example 8 | Example 9 | |
| Bilobalide | 50g | 10g | 200g | 50g | 50g | 50g | 50g | 50g | 50g |
| Low-substituted hydroxypropyl cellulose | 10g | 5g | 5g | 10g | 10g | 10g | 10g | ||
| Carboxymethyl starch sodium | 5g | 5g | 20g | ||||||
| Cross-linking sodium carboxymethyl cellulose | 3g | 30g | |||||||
| Polyvinylpolypyrrolidone | 7g | 30g | 20g | 20g | 20g | ||||
| Microcrystalline Cellulose | 100g | 300g | 100g | 100g | 60g | 300g | 200g | ||
| Mannitol | 50g | 200g | 100g | ||||||
| Sodium lauryl sulphate | 2g | 1g | 10g | 2g | 2g | 2g | 2g | 2g | 2g |
| Anhydrous citric acid | 5g | 3g | 10g | 5g | 5g | 5g | 5g | 5g | 5g |
| Sodium bicarbonate | 7g | 5g | 15g | 7g | 7g | 7g | 7g | 7g | 7g |
| Micropowder silica gel | 5g | 1.5g | 5g | 3g | 3g | 3g | 3g | 3g | 3g |
| Magnesium stearate | 1g | 0.2g | 2g | 1g | 1g | 1g | 1g | 1g | 1g |
| Correctives | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount |
| Make (sheet) | 1000 | 1000 | 1000 | 1000 | 1000 | 1000 | 1000 | 1000 | 1000 |
| Bilobalide content (mg/ sheet) | 50 | 10 | 200 | 50 | 50 | 50 | 50 | 50 | 50 |
Oral cavity disintegration tablet pharmacodynamics test of the present invention
1, medicine and reagent
Claimed by the reagent name: oral cavity disintegration tablet of the present invention; Nimodipine tablet: the inferior precious Pharmaceutical in Shanxi limited company: chloral hydrate: A.R, China Medicine (Group) Shanghai Chemical Reagent Co.; 0.9% sodium chloride injection: state-run Zhangjagang City pharmaceutical factory; Red tetrazolium (TTC): A.R, China Medicine (Group) Shanghai Chemical Reagent Co.,, 10g/ bottle; Azovan blue: China Medicine (Group) Shanghai Chemical Reagent Co.; Aspirin Enteric-coated Tablets, 25mg/ sheet, Nanjing Hencer Pharmaceutical Factory; Heparin sodium: the emerging biochemical reagents company limited of Chinese favour (Shanghai); Pentobarbital sodium: China Medicine (Group) Shanghai Chemical Reagent Co.; 10% glucose injection: Shangdong Hualu Pharmaceutical Co., Ltd.; Aspirin Enteric-coated Tablets, Nanjing Hencer Pharmaceutical Factory; AA (arachidonic acid): specification 100mg/ bottle is provided by sigma company.Platelet activating factor (PAF), specification: 1mg/ props up, and sigma company provides.Trisodium citrate: specification: the 500g/ bottle, AR, the magnificent forever fine chemicals company limited in Changshu City is produced.
2, experimental apparatus
The little electric knife of 1411 high frequencies, Shanghai Medical Instrument High Technology Company; The desk-top drying baker of WG2003, Chongqing Wanda's company limited; JA3003 electronic balance: go up balance equipment factory of Nereid section; SJ-42 polygraph: Shanghai Medical Electric Instrument Factory; XX-1 type thrombosis monitor, the blue or green medical instrument of Nanhui, Shanghai woods factory; RM6000 type polygraph, Nihon Koden; The MFV-3200 electromagnetic flowmeter, Nihon Koden; The MFV-1200 electromagnetic flowmeter, NihonKoden; KHW-501 constant temperature sulculus, Jiangsu ultrasonic device factory; PAPER-I type platelet aggregation and blood clotting analyzer, Beijing Steellex Scientific Instrument Company; The LDZ5-2 centrifuge, Beijing Medical Centrifugal Machine Factory; HH-2 digital display thermostat water bath state China Electrical Appliances Co., Ltd.
3, experimental animal
The SD rat, body weight 250～300g, The 2nd Army Medical College Experimental Animal Center; White big ear rabbit, male, 2.0～2.3kg is provided by Nanjing An Limo Science and Technology Ltd..
Experimental technique and result:
(1) Orally disintegrating tablet of ginkgolide is to the protective effect of rat experiment focal cerebral ischemia
Get the SD rat, body weight 250～300g is divided into 6 groups at random by the body weight sex, and 10 every group, male and female half and half.Be respectively Orally disintegrating tablet of ginkgolide high dose group 60.0mg/kg (in bilobalide, down together), middle dosage group 30.0mg/kg, low dose group 15.0mg/kg, positive control nimodipine group 12mg/kg (1.2mg/ml), sham operated rats and ischemia model matched group (all giving equivalent 0.5%CMC-Na).In preceding four days of experiment, be administered once every day, and gastric infusion is 4 days continuously.The 4th day for the last time in ischemia administration in preceding 30 minutes.Adopt internal carotid artery line bolt legal system to be equipped with intraluminal middle cerebral artery occlusion in rats obturation (MCAO) model: rat is anaesthetized with 10% chloral hydrate (300mg/kg) ip, the cervical region median incision on the operating-table of lying on the back, expose right carotid, outwards draw digastric and sternocleidomastoid, free successively by common carotid artery crotch head-end, ligation and the branch of cutting off external carotid artery: tremulous pulse and superior thyroid artery under the occipital bone.In the ligation of external carotid artery far-end, cut off external carotid artery and make its trunk free standby.Separate internal carotid artery then, make a call to one with silk thread at the external carotid artery root and release, folder closes common carotid artery and internal carotid artery.With nylon wire (long 4cm, diameter 0.26mm) through external carotid artery trunk otch, slowly going into the cranium direction to internal carotid artery advances, with the common carotid artery crotch is labelling, feel resistance when advancing the 18mm left and right sides, promptly reached in the thinner anterior cerebral artery, all blood of having blocked MCA are tightened the external carotid artery root and are released for the source.After one hour, extract nylon wire, tighten the tremulous pulse stump.Skin suture is finished MCAO and is caused focal cerebral ischemia-irritate again model.Behind the sham operated rats rat anesthesia, only expose the inside and outside aortic bifurcation of neck, not inaccessible MCA.
By the method for Bederson the behavioral deficiency of animal is carried out rank scores behind the MCAO 24h, standard is as follows:
0 minute: do not observe nervous symptoms;
1 minute: carry tail when unsettled, the operation offside forelimb of animal showed as wrist elbow flexing, the shoulder inward turning, and the elbow abduction is close to thoracic wall;
2 minutes: animal is placed on the smooth flat, and pushing hands art side was takeed on to side shifting the time, and resistance reduces;
3 minutes: side ring is changeed or turn-take to operation during the animal walking freely;
4 minutes; Collapse from physical exhaustion, limbs do not have spontaneous activity.
24h sacrificed by decapitation rat behind the MCAO, it is fixing in 10% formalin to take out full brain, get the brain coronal section, dehydration, paraffin embedding, film-making (4 μ m), HE dyeing, under optical microscope, read sheet by the pathology professional, observe its cerebral cortex hippocampus morphocytology and change, be designated as respectively according to lesion degree: "-" "+" " ++ " " +++".
Normal control group (pseudo-operation group):
10 routine cerebral tissue cerebral cortex and hippocampus neuron (pyramidal cell) are normal substantially, and nuclear is placed in the middle, does not see pathological changes such as the obvious degeneration of neuron, necrosis and cell infiltration.
Model control group:
During 10 routine brain cell cerebral cortex and CA1-CA3 hippocampus neuron (pyramidal cell) are all seen-severe degeneration, necrosis (++～+++).Neuronal structure is fuzzy, cell space swelling, Nissl body reduces or disappear, and in various degree nuclear hyperchromatism, karyopycnosis, karyolysis occur, and the neuron number obviously reduces.
Nimodipine group (positive drug group):
There are 8 routine cerebral tissue not see pathological changes such as obvious neuronal degeneration, necrosis and cell infiltration in the 10 routine cerebral tissue.2 routine cerebral tissue CA1-CA3 hippocampus neurons (pyramidal cell) take a favourable turn-moderate degeneration, necrosis (+), neuronal structure is fuzzy, cell space swelling, Nissl body reduces or disappear, in various degree nuclear hyperchromatism, karyopycnosis, karyolysis occur, the neuron number increases than model control group.
The bilobalide low dose group:
There are 5 routine cerebral tissue not see pathological changes such as obvious neuronal degeneration, necrosis and cell infiltration in the 10 routine cerebral tissue.5 routine cerebral tissue CA1-CA3 hippocampus neurons (pyramidal cell) take a favourable turn-severe degeneration, necrosis (+～+++), and neuronal structure is fuzzy, cell space swelling, Nissl body reduces or disappear, and in various degree nuclear hyperchromatism, karyopycnosis, karyolysis occur.
Dosage group in the bilobalide:
There are 7 routine cerebral tissue not see pathological changes such as obvious neuronal degeneration, necrosis and cell infiltration in the 10 routine cerebral tissue.3 routine cerebral tissue CA1-CA3 hippocampus neurons (pyramidal cell) take a favourable turn-moderate degeneration, necrosis (+～++), neuronal structure is fuzzy, cell space swelling, Nissl body reduces or disappear, in various degree nuclear hyperchromatism, karyopycnosis, karyolysis occur, the neuron number increases than model control group.
The bilobalide high dose group:
There are 8 routine cerebral tissue not see pathological changes such as obvious neuronal degeneration, necrosis and cell infiltration in the 10 routine cerebral tissue.2 routine cerebral tissue CA1-CA3 hippocampus neurons (pyramidal cell) take a favourable turn-moderate degeneration, necrosis (+～++), neuronal structure is fuzzy, cell space swelling, Nissl body reduces or disappear, in various degree nuclear hyperchromatism, karyopycnosis, karyolysis occur, the neuron number increases than model control group.
(2) Orally disintegrating tablet of ginkgolide is to the influence of platelet function
1, bilobalide is to the thrombotic influence of rabbit Chandler
Adopt the Chandler method, get 40 of male rabbits, be divided into 5 groups at random, 8 every group, Orally disintegrating tablet of ginkgolide high dose group 30mg/kg, middle dosage group 15mg/kg, low dose group 7.5mg/kg; Solvent control group (0.5%CMC), aspirin (ASP) group 15mg/kg.Gastric infusion, administration every day 1 time, successive administration 5 days; 45min after the administration in the 5th day, back of the body position is fixed on the operating-table.Adopt 10mg.ml
-1The procaine hydrochloride local anaesthesia, separate a side common carotid artery and make the common carotid artery intubate, getting blood 2ml with disposable syringe from common carotid artery injects in the polyethylene pipe ring, thrombosis is after the thrombosis instrument rotates 15 minutes, removal of thromboses in ring blots blood, weighing weight in wet base at once, 60 ℃ of dryings 30 minutes, the weighing dry weight.Calculate dry weight suppression ratio (the results are shown in following table).
Suppression ratio=(matched group thrombosis dry weight-administration group thrombosis dry weight)/matched group thrombosis dry weight * 100%
| Group | Dosage (mg/kg) | Wet weight of thrombus (mg) | Thrombosis dry weight (mg) | Suppression ratio |
| The solvent control group | - | 80.88±13.11 | 26.25±6.67 | - |
| Aspirin | 15 | 41.13+11.48 ** | 10.25±3.06 ** | 60.95 |
| Bilobalide | 30 15 7.5 | 48.13+9.64 ** 58.00±16.65 ** 69.00±12.77 | 12.25±3.01 ** 16.13±4.39 ** 22.00±5.42 | 53.33 38.57 16.19 |
*P＜0.05,
*Compare with the solvent control group P＜0.01
The result shows that Orally disintegrating tablet of ginkgolide height, middle dosage group all have the effect of obvious inhibition rabbit Chandler thrombosis, more all have utmost point significant difference (P＜0.01) with the solvent control group.High, middle dosage group thrombosis dry weight suppression ratio is respectively 53.33% and 38.57%.
2, Orally disintegrating tablet of ginkgolide is to the influence of rabbit platelet aggregation
Grouping and medication: rabbit is divided into 5 groups at random: normal control group (isometric(al) CMC-Na), positive controls aspirin (10.0mg/kg), Orally disintegrating tablet of ginkgolide high dose (32.0mg/kg), middle dosage (16mg/kg), low dosage (8mg/kg).Gastric infusion, every day 1 time, for three days on end.
Platelet aggregation rate detects: 20min (positive controls is 60min after administration) neck is always got blood behind the 3rd day drug administration by injection, sodium citrate (3.8%) anticoagulant in 1: 9, with the centrifugal 10min of 1000r/min, get platelet rich plasma (PRP), remainder is centrifugal with 3000r/min, get platelet poor plasma (PPP), aggregation inducing agent PAF (final concentration 0.38 μ g/ml), ADP (5.54ug/ml), AA (76.9ug/ml).Measure platelet 1min, 5min, max aggregation rate with PAPER-I type platelet aggregation and blood clotting analyzer, and calculate suppression ratio by following formula.
Orally disintegrating tablet of ginkgolide shows the experimental result that influences of rabbit at the body platelet aggregation rate: three dosage of bilobalide gastric infusion all can suppress the hematoblastic maximum agglutination rate of the inductive rabbit of ADP, and middle dosage also has inhibitory action (seeing Table A) to 1min, 5min aggregation rate; Bilobalide height, middle dosage have inhibitory action to hematoblastic 1min of the inductive rabbit of PAF and maximum agglutination rate, and high dose also has inhibitory action (seeing Table B) to the 5min aggregation rate; Bilobalide height, middle dosage have inhibitory action (seeing Table C) to the hematoblastic 5min of the inductive rabbit of AA, maximum agglutination rate.
Table A. bilobalide is induced the influence of rabbit platelet aggregation rate-(X ± SD) to ADP
| Group | Dosage mg/kg | Number of animals | Platelet aggregation rate % | Assemble suppression ratio % | ||
| 1min | 5min | Max | ||||
| Normal control | Isometric(al) | 6 | 34.93±9.53 | 48.15±14.74 | 55.93±10.72 | |
| Aspirin | 10.0 | 6 | 18.91±5.25 ** | 30.78±4.18 * | 32.85±4.63 ** | 41.27 |
| Bilobalide | 32 16 8 | 6 6 6 | 27.48±4.53 20.38±5.16 **29.65±2.00 | 31.93±13.67 26.64±4.01 **38.27±5.67 | 37.76±8.62 **30.46±4.00 **43.73±3.33 * | 32.49 45.54 21.81 |
Annotate: compare with model group
*P＜0.05
*P＜0.01 (down together)
Table B. bilobalide is induced the influence of rabbit platelet aggregation rate-(X ± SD) to PAF
| Group | Dosage mg/kg | Number of animals | Platelet aggregation rate % | Assemble suppression ratio % | ||
| 1min | 5min | Max | ||||
| Normal control | Isometric(al) | 6 | 24.73±0.89 | 43.72±2.26 | 44.91±2.19 | |
| Aspirin | 10.0 | 6 | 19.57±2.56** | 27.79±4.10** | 30.28±4.08** | 32.58 |
| Bilobalide | 32 16 8 | 6 6 6 | 20.2±3.46* 21.84±1.21** 23.39±2.12 | 26.47±14.65* 31.38±13.69 41.19±3.56 | 31.43±9.04** 35.68±5.38** 41.88±3.58 | 30.02 20.55 6.75 |
Table C. bilobalide is induced the influence of rabbit platelet aggregation rate-(X ± SD) to AA
| Group | Dosage mg/kg | Number of animals | Platelet aggregation rate % | Assemble suppression ratio % | ||
| 1min | 5min | Max | ||||
| Normal control | Isometric(al) | 6 | 26.93±3.04 | 53.41±6.22 | 55.59±5.73 | |
| Aspirin | 10.0 | 6 | 20.13±3.68 ** | 34.12±13.34 ** | 36.48±12.53 ** | 34.38 |
| Bilobalide | 32 16 8 | 6 6 6 | 28.62±2.70 24.23±3.11 29.04±2.61 | 44.64±5.45 *36.70±8.71 **49.57±3.86 | 46.15±4.92 *39.74±6.60 **51.22±3.03 | 16.98 28.51 7.86 |
Annotate: compare with model group
*P＜0.05
*P＜0.01 (down together)
Conclusion (of pressure testing)
Behind Orally disintegrating tablet of ginkgolide height, the middle dosage group focal cerebral ischemia 24h, histopathologic examination shows that bilobalide can obviously improve the brain metabolism of rat under the focal cerebral ischemia; Keep the normal morphology and the function of neurocyte under the cerebral ischemic condition, delay, alleviate its necrosis.
Orally disintegrating tablet of ginkgolide height, middle dosage group all have the effect of obvious inhibition rabbit Chandler thrombosis, with the solvent control group utmost point significant difference (P＜0.01) are arranged more all.The highest thrombosis dry weight suppression ratio can reach 45.59%.
Bilobalide vivo medicine-feeding and treated in vitro have the obvious suppression effect to the inductive rabbit platelet aggregation rate of PAF, and inhibiting power and dosage are dependence.
Claims (6)
1, Orally disintegrating tablet of ginkgolide, it is characterized in that basically by 1 part of bilobalide, 0.1～1 part of low-substituted hydroxypropyl cellulose and/or carboxymethyl starch sodium and/or cross-linking sodium carboxymethyl cellulose and/or polyvinylpolypyrrolidone disintegrating agent, 1～10 part of microcrystalline Cellulose and/or mannitol filler, 0.01～0.1 part of sodium lauryl sulphate surfactant, 0.05～0.5 part of anhydrous citric acid and/or sodium bicarbonate are formed.
2,, it is characterized in that said bilobalide lactone total content 〉=70%, ginkalide B content 〉=40% according to the described Orally disintegrating tablet of ginkgolide of claim 1.
3,, it is characterized in that said filler is 1.5～3 parts according to the described Orally disintegrating tablet of ginkgolide of claim 1.
4, according to claim 1,2 or 3 described Orally disintegrating tablet of ginkgolide, it is characterized in that also adding fluidizer such as an amount of micropowder silica gel, magnesium stearate.
5,, it is characterized in that also adding an amount of correctives according to the described Orally disintegrating tablet of ginkgolide of claim 4.
6, according to the preparation of the described Orally disintegrating tablet of ginkgolide of claim 1-5, it is characterized in that required supplementary material is crossed 100 mesh sieves respectively, standby; Take by weighing the abundant mix homogeneously of adjuvant respectively by prescription; The bilobalide that adds recipe quantity is with the abundant mixing of above-mentioned adjuvant, compressing dry granulation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CNA2006100403737A CN1883472A (en) | 2006-05-19 | 2006-05-19 | Orally disintegrating tablet of ginkgolide and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100403737A CN1883472A (en) | 2006-05-19 | 2006-05-19 | Orally disintegrating tablet of ginkgolide and preparation method thereof |
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| CN1883472A true CN1883472A (en) | 2006-12-27 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103976967A (en) * | 2014-06-04 | 2014-08-13 | 湖南科技学院 | Ginkgolide sublingual tablet and preparation method thereof |
| CN113995728A (en) * | 2020-07-28 | 2022-02-01 | 江苏康缘药业股份有限公司 | Pharmaceutical composition and preparation method thereof |
-
2006
- 2006-05-19 CN CNA2006100403737A patent/CN1883472A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103976967A (en) * | 2014-06-04 | 2014-08-13 | 湖南科技学院 | Ginkgolide sublingual tablet and preparation method thereof |
| CN113995728A (en) * | 2020-07-28 | 2022-02-01 | 江苏康缘药业股份有限公司 | Pharmaceutical composition and preparation method thereof |
| CN113995728B (en) * | 2020-07-28 | 2023-03-14 | 江苏康缘药业股份有限公司 | Medicinal composition and preparation method thereof |
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Open date: 20061227 |