CN101439059A - Ginkgo leaf extract drop and preparation method thereof - Google Patents
Ginkgo leaf extract drop and preparation method thereof Download PDFInfo
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- CN101439059A CN101439059A CNA2007101777417A CN200710177741A CN101439059A CN 101439059 A CN101439059 A CN 101439059A CN A2007101777417 A CNA2007101777417 A CN A2007101777417A CN 200710177741 A CN200710177741 A CN 200710177741A CN 101439059 A CN101439059 A CN 101439059A
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Abstract
The invention discloses ginkgo biloba extract drops. The pharmaceutical active component of the ginkgo biloba extract drops is ginkgo biloba extract, and the proportion by weight between the ginkgo biloba extract and other accessories ranges from 1:5 to 1:25.5; and in detail, the ginkgo biloba extract drops are prepared by using the ginkgo biloba extract and the accessories according to the following parts by weight: 1 part of the ginkgo biloba extract, and 2 parts to 25 parts of thinner, 1 part to 20 parts of latent solvent and 0.01 part to 2 parts of flavoring, which serve as the accessories. Compared with a solid preparation, the ginkgo biloba extract drops are more quickly absorbed in bodies and have high bioavailability; compared with oral liquid or a grain preparation, the ginkgo biloba extract drops have no first-pass effect; compared with the oral liquid, the ginkgo biloba extract drops have the advantages of high stability, accurate dose, small dose and convenient use; compared with dripping pills, the ginkgo biloba extract drops have the advantages of quick acting, small dose, convenient use, and the like; and the production process of the ginkgo biloba extract drops is simple and has low cost, and the ginkgo biloba extract drops are adapted to large-scale production, and pollution does not easily occur during the production; and the ginkgo biloba extract drops overcome the defect that the taking of the dripping pills requires the dissolution by sputum, and the ginkgo biloba extract drops are suitable for suffers of various types. The quality of the drops is standard and perfect and quality control during the production can be facilitated.
Description
Technical field
The present invention relates to a kind of ginkgo leaf extract drop and preparation method thereof, belong to the field of Chinese medicines.
Background technology
Folium Ginkgo extract is the effective site of extracting from the Folium Ginkgo medical material, and the main chemical compositions that contains is total flavonoids, terpene lactone etc.
Modern age, pharmaceutical research and main pharmacodynamics clinical trial showed, ginkgetin has obvious blood fat reducing, cholesterol reducing effect, increased the coronary blood liquid measure, reduced myocardial oxygen consumption, microcirculation improvement.It still is a kind of free radical scavenger, so defying age, antitumaous effect are arranged.Folium Ginkgo lactone B is the antagonist of platelet activating factor (PAF), has anticoagulation, reduces blood viscosity, improves blood flowing characteristic, prevents thrombosis, promotes thrombolytic effect.Thereby since the eighties, Folium Ginkgo extract and preparation have become the focus of the world of medicine's research and development.Folium Ginkgo extract (GBE) is listed in treatment cardiovascular and cerebrovascular disease, dementia and antidotal important drugs.Be applicable to ischemic cardio cerebrovascular diseases, hypertension, hyperlipidemia, arteriosclerosis, coronary heart disease, angina pectoris, cerebral embolism, cerebral vasospasm, brain insufficiency, senile dementia, parkinson, apoplexy, myocardial infarction, allergic asthma, prolonged application can hypermnesis, slow down aging.And take substantially for a long time and have no side effect.
The existing peroral dosage form that contains the Folium Ginkgo extract has capsule, tablet, granule, oral liquid, drop pill etc.Because of capsule, tablet are solid preparation, the patient is when taking, and drug releasing rate is slow, and onset is slow, and bioavailability is low; Oral liquid and granule need dosage bigger when taking, and belong to gastrointestinal mucosa and absorb, and bioavailability is low, and the process of taking is not suitable for the patient with severe symptoms and takes.In order to address the above problem, those skilled in the art are prepared into drop pill with Folium Ginkgo extract, its advantage be quick-acting, efficient, take, easy to carry; But the technological operation step complexity in the drop pill production process, require high to production equipment and operating environment, all is quite strict for the height of fluid temperature, condensed fluid, drip apart from the requirement of the temperature of the distance of condensed fluid and ice bath, has deviation promptly can influence profile, adhesion degree and the hangover etc. of drop pill slightly.Drop pill quality examination strictness, outward appearance is answered glomeration, size is even, the color and luster unanimity, and weight differential also has quite strict requirement, as get drop pill 20 balls, the accurate title, decide gross weight, try to achieve average ball heavy after, claim to decide each ball weight accurate respectively, every ball weight must not surpass 2 balls with the drop pill that average ball heavy phase relatively exceeds limit test of weight variation, and one times of a ball overrun must not be arranged.The drop pill production cost is too high in view of the foregoing, the crowd of clinical practice is only limited to economic base colony's scope preferably, ordinary consumer is beyond affordability economically, and drop pill is a buccal absorption, no first pass effect, must need the oral cavity to possess saliva, can be with the drop pill disintegrate, then inconvenience use of some patient with severe symptoms's saliva of buccal cavity amount rarenesses clinically.
In view of the problems referred to above that prior art exists, be badly in need of a kind of can buccal absorption, no first pass effect, good effect, onset are rapid again, pharmaceutical applications crowd is in extensive range, the efficient ginkgo leaf extract preparation that price is relatively low.
Summary of the invention
The objective of the invention is to solve and remedy the defective of prior art, propose a kind of can buccal absorption, good effect, instant effect, no first pass effect and preparation method be simple, with low cost, suitable crowd is ginkgo leaf extract drop widely.
Another purpose of the present invention is to provide the preparation method of above-mentioned ginkgo leaf extract drop.
To achieve these goals, the present invention adopts following technical scheme:
Folium Ginkgo and Folium Ginkgo extract contain the bioactive substance that can resist multiple disease and slow down aging, wherein ginkgetin glycosides and terpene lactones (GBE-HP) have vasodilator, microcirculation improvement effect, particularly remarkable to big cerebral circulatory disorders and cerebral arteriosclerosis therapeutic effect; Can promote the heart and brain blood flow, improve brain nutrition, overcome disordered brain function; Cholesterol reducing and hyperlipidemia, antagonism platelet activating factor activity has regulating action to cerebral thrombus patient's cerebral circulation, glucose metabolism; Have the effect of superoxide dismutase sample, remove free radical, it is aging to delay the blood cerebrovascular, to the free radical diseases associated, as alzheimer disease, aging, diseases of cardiovascular and cerebrovascular systems the improvement effect is arranged all.
The present invention is beyond thought to have found that Folium Ginkgo extract is made drop can be absorbed through the oral cavity, required dosage is little, instant effect, verify through Experiment of Zoology, Folium Ginkgo drop of the present invention does not have first pass effect than other preparations of Folium Ginkgo, the bioavailability height, it is auxiliary to need not saliva in clinical practice, and the scope of application is extensive.And this drop preparation method is simple, with low cost.
The concrete technical scheme of the present invention is as follows:
A kind of ginkgo leaf extract drop, its active constituents of medicine are Folium Ginkgo extract, and the weight ratio of Folium Ginkgo extract and other adjuvants is 1:5~1:25.5; It specifically is to be made by the Folium Ginkgo extract of following weight portion proportioning, adjuvant:
1 part of Folium Ginkgo extract;
Adjuvant: 2~25 parts of diluent; 1~20 part of cosolvent; 0.01~2 part of correctives.
Above-mentioned a kind of ginkgo leaf extract drop, wherein, described diluent is one or more in water, propylene glycol, glycerol, the PEG400.
Above-mentioned a kind of ginkgo leaf extract drop, wherein, described cosolvent is one or more in water, medicinal alcohol, glycerol, the PEG400.
Above-mentioned a kind of ginkgo leaf extract drop, wherein, described correctives is a kind of in protein sugar, nectar source sugar, the sweet close element.
Above-mentioned a kind of ginkgo leaf extract drop, wherein, described Folium Ginkgo extract is 100~200 order spray drying fine powders, contains moisture less than 3%.
The present inventor is through long term test and Experiment of Zoology checking, drawn the ratio of greater inequality of above-mentioned drop active constituents of medicine and adjuvant and the optimum weight proportion of each adjuvant.The inventor finds:
1. diluent concentration has certain influence to the quality of drop, concentration hour, and the stability of medicinal liquid and clarity are poor slightly; When concentration was big, the stability and the clarity of medicinal liquid were better, and it is influential to the drop quality to illustrate that diluent accounts for whole drop concentration, and were the best with 20~90% concentration ranges.
2. cosolvent concentration also has certain influence to the quality of drop, concentration hour, and the stability of medicinal liquid and clarity are poor slightly; When concentration was big, the stability and the clarity of medicinal liquid were better, and it is influential to the drop quality to illustrate that cosolvent accounts for the concentration of whole drop, and were the best with 10~80% concentration ranges.
Mouthfeel was influential when 3. the agent of sedan-chair flavor was taken drop, and concentration is low, took back mouthfeel hardship, the concentration height, and it is too sweet to take the back mouthfeel, illustrate to distinguish the flavor of sedan-chair to account for the concentration of whole drop influential to taking quality in agent, and is the best with 0.01~5% concentration range.
4. crude drug powder fineness, the speed of being sprinkled into are to influence dissolved key in the preparation process, raw material medicated powder is thick, it is fast to be sprinkled into the mixed liquor medium velocity, fine powder is assembled mutually, and big agglomerate increases, and dissolution velocity is very slow, the dosing time lengthening, on the contrary, raw material medicated powder is thin, be sprinkled into that medicated powder is even, speed is moderate, and dissolution velocity is very fast, the dosing process is finished comparatively fast, can shorten the production cycle.So raw material medicated powder is the best with 100~200 order spray drying powders; Being sprinkled into and being sprinkled into medicated powder again after medicated powder speed is dissolved substantially with the liquid level medicated powder of mixed solution is the best.
Therefore as can be seen, cosolvent, diluent concentration be the whole dosing process of influence than key factor, determine optium concentration, fineness, speed so should look concrete condition.
According to said ratio, the preparation method of a kind of ginkgo leaf extract drop of the present invention is characterized in that it comprises the following steps:
(1) gets the raw materials ready: take by weighing Folium Ginkgo extract and each adjuvant by the described weight portion of claim 1;
(2) cosolvent, an amount of diluent, the agent of sedan-chair flavor are mixed, stir and make mixed solution;
(3) be mixed at above-mentioned mixed solution and when liquid level does not have medicated powder Folium Ginkgo extract at the uniform velocity added, dissolving and mix homogeneously;
(4) amount of being adjusted to: add water and be adjusted to ormal weight, promptly make the ginkgo leaf extract drop medicinal liquid.
(5) packing: the medicine liquid irrigation that makes is packed in the bottle into sealing;
(6) inspection and evaluation: preparation is carried out quality evaluation and study on the stability.
Step of the present invention (3) mixed process can be utilized ultrasonic dissolution method, heating for dissolving method or stirring and dissolving method.The temperature of heating for dissolving is that 40~50 degree are best.
Every 1ml contains total flavonoids and is no less than 9.6mg, contains the content sum of terpene lactone in bilobalide (C15H18O8), ginkalide A (C20H24O9), ginkalide B (C20H24O10), ginkalide C (C20H24O11) in the ginkgo leaf extract drop of the present invention preparation, is no less than 2.4mg.
Ginkgo leaf extract drop character of the present invention is a rufous supernatant liquid preparation, can direct packaging in the bottle of brown PC or PET material.Splash into about 2ml in the use at every turn; Because the present invention is without any side effects, concrete access times and use amount can be abideed by doctor's advice and take according to the symptom of clinical practice embodiment.
The ginkgo leaf extract drop of the present invention's preparation is compared with tablet, capsule, oral liquid, granule, the drop pill of prior art and is had following advantage and benefit:
(1) ginkgo leaf extract drop of the present invention belongs to liquid preparation, compares with the Folium Ginkgo extract solid preparation, and medicine infiltration rate in vivo is very fast, and bioavailability is higher;
(2) ginkgo leaf extract drop of the present invention and ginkgo leaf extract oral liquid, granule compare, and drop belongs to oral mucosa and absorbs no first pass effect; With oral liquid relatively, drop has increased stability of drug, it is accurate to have dosage, dose is few, the advantage of taking convenience;
(3) though drop of the present invention and the comparison of Folium Ginkgo extract drop pill all are oral mucosal absorbent preparations, have efficient, quick-acting, advantages such as taking dose is little, taking convenience, but the operating procedure of ginkgo leaf extract drop production process is simple, production cost is low, be fit to large-scale production, production process is difficult for polluting, and the operating procedure complexity of Folium Ginkgo extract drop pill production process, the production cost height; Application facet clinically, ginkgo leaf extract drop is because cost is low, and price is moderate relatively, and suitable consumption patient is in extensive range; The Folium Ginkgo extract drop pill in use need dissolve through saliva, for the part patient, the no saliva disease patient who causes as nasopharyngeal carcinoma then can not well take, and ginkgo leaf extract drop of the present invention has overcome this defective of prior art, is applicable to all kinds of patients.
(4) ginkgo leaf extract drop quality standard of the present invention is perfect, is convenient to produce control of quality.
The preparation method emphasis of ginkgo leaf extract drop of the present invention adopts Folium Ginkgo extract to add finite concentration cosolvent, diluent, the agent of sedan-chair flavor and is prepared into drop, at present, also do not find Chinese medicine and make the medicine that code is produced in the acquisition of drop, the drop preparation method is simple, and is with low cost, the product quality height, at home good market prospect and development space will be arranged, it has following advantage and benefit: 1. production process is simple, and production capacity is big, cost of equipment is lower, is fit to suitability for industrialized production; 2. the dosing process time by the crude drug powder fineness, be sprinkled into mixed liquor speed decision, relatively easy control, the medicinal liquid clarity of preparation, good stability; 3. the drop medicinal liquid mix homogeneously that makes, the content of the active component that contains is even.
The specific embodiment
Each raw material sources in the specific embodiment of the invention:
1, Folium Ginkgo extract fine powder: water content is less than 3%: Kang Enbei pharmaceutical Co. Ltd in Zhejiang produces
2, PEG400: Nanjing WeiEr chemical engineering Co., Ltd's pharmaceutical grade
3, propylene glycol: Nanjing WeiEr chemical engineering Co., Ltd's pharmaceutical grade
4, medicinal alcohol: Weifang, Shandong Gene Kelly chemical industry company limited pharmaceutical grade
5, glycerol: the safe chemical industry company limited of Shanghai gold trade import pharmaceutical grade
6, protein sugar: Hengshui, Hebei new photoinitiator chemical company limited food stage
7, nectar source sugar: Hengshui, Hebei new photoinitiator chemical company limited food stage
8, cyclamate: Hengshui, Hebei new photoinitiator chemical company limited food stage
Embodiment 1
(1) gets the raw materials ready: take by weighing former, adjuvant by following weight;
Folium Ginkgo extract 40g
PEG400 222g
Propylene glycol 100g
Medicinal alcohol 120g
Protein sugar 25g
Folium Ginkgo extract and adjuvant weight ratio are 1:11.6;
(2) PEG400, propylene glycol, medicinal alcohol and protein sugar are mixed, stir, be prepared into mixed solution;
(3) when above-mentioned mixed solution is mixed to liquid level and does not have medicated powder, Folium Ginkgo extract is at the uniform velocity joined in the mixed solution of step (2) preparation, adopt the dissolving of excusing from death dissolution method, mix homogeneously;
(4) amount of being adjusted to: add water and be adjusted to ormal weight 1000ml, make the ginkgo leaf extract drop medicinal liquid;
(5) packing: the medicine liquid irrigation that makes is packed in the bottle into sealing.
Embodiment 2
(1) gets the raw materials ready: take by weighing former, adjuvant by following weight;
Folium Ginkgo extract 40g
PEG400 277.5g
Propylene glycol 100g
Medicinal alcohol 96g
Protein sugar 20g
Folium Ginkgo extract and adjuvant weight ratio are 1:12.3;
(2) PEG400, propylene glycol, medicinal alcohol and protein sugar are mixed, stir, be prepared into mixed solution;
(3) when above-mentioned mixed solution is mixed to liquid level and does not have medicated powder, Folium Ginkgo extract is at the uniform velocity joined in the mixed solution of step (2) preparation, adopt the dissolving of excusing from death dissolution method, mix homogeneously;
(4) amount of being adjusted to: add water and be adjusted to ormal weight 1000ml, make the ginkgo leaf extract drop medicinal liquid;
(5) packing: the medicine liquid irrigation that makes is packed in the bottle into sealing.
Embodiment 3
(1) gets the raw materials ready: take by weighing former, adjuvant by following weight;
Folium Ginkgo extract 40g
PEG400 277.5g
Medicinal alcohol 96g
Protein sugar 30g
Folium Ginkgo extract and adjuvant weight ratio are 1:10.1;
(2) PEG400, medicinal alcohol and protein sugar are mixed, stir, be prepared into mixed solution;
(3) when above-mentioned mixed solution is mixed to liquid level and does not have medicated powder, Folium Ginkgo extract is at the uniform velocity joined in the mixed solution of step (2) preparation, adopt the dissolving of excusing from death dissolution method, mix homogeneously;
(4) amount of being adjusted to: add water and be adjusted to ormal weight 1000ml, make the ginkgo leaf extract drop medicinal liquid;
(5) packing: the medicine liquid irrigation that makes is packed in the bottle into sealing.
Embodiment 4
(1) gets the raw materials ready: take by weighing former, adjuvant by following weight;
Folium Ginkgo extract 40g
PEG400 333g
Medicinal alcohol 160g
Protein sugar 40g
Folium Ginkgo extract and adjuvant weight ratio are 1:13.3;
(2) PEG400, medicinal alcohol and protein sugar are mixed, stir, be prepared into mixed solution;
(3) when above-mentioned mixed solution is mixed to liquid level and does not have medicated powder, Folium Ginkgo extract is at the uniform velocity joined in the mixed solution of step (2) preparation, adopt the dissolving of stirring and dissolving method, mix homogeneously;
(4) amount of being adjusted to: add water and be adjusted to ormal weight 1000ml, make the ginkgo leaf extract drop medicinal liquid;
(5) packing: the medicine liquid irrigation that makes is packed in the bottle into sealing.
Embodiment 5
(1) gets the raw materials ready: take by weighing former, adjuvant by following weight;
Folium Ginkgo extract 40g
PEG400 444g
Medicinal alcohol 120g
Glycerol 50g
Protein sugar 40g
Folium Ginkgo extract and adjuvant weight ratio are 1:16.4;
(2) PEG400, medicinal alcohol, glycerol and protein sugar are mixed, stir, be prepared into mixed solution;
(3) when above-mentioned mixed solution is mixed to liquid level and does not have medicated powder, Folium Ginkgo extract is at the uniform velocity joined in the mixed solution of step (2) preparation, adopt the dissolving of heating for dissolving method, 40~50 ℃ of mix homogeneously of solution temperature;
(4) amount of being adjusted to: add water and be adjusted to ormal weight 1000ml, make the ginkgo leaf extract drop medicinal liquid;
(5) packing: the medicine liquid irrigation that makes is packed in the bottle into sealing.
Embodiment 6
(1) gets the raw materials ready: take by weighing former, adjuvant by following weight;
Folium Ginkgo extract 40g
PEG400 555g
Medicinal alcohol 160g
Glycerol 100g
Protein sugar 40g
Folium Ginkgo extract and adjuvant weight ratio are 1:21.4;
(2) PEG400, medicinal alcohol, glycerol and protein sugar are mixed, stir, be prepared into mixed solution;
(3) when above-mentioned mixed solution is mixed to liquid level and does not have medicated powder, Folium Ginkgo extract is at the uniform velocity joined in the mixed solution of step (2) preparation, adopt the dissolving of ultrasonic dissolution method, mix homogeneously;
(4) amount of being adjusted to: add water and be adjusted to ormal weight 1000ml, make the ginkgo leaf extract drop medicinal liquid;
(5) packing: the medicine liquid irrigation that makes is packed in the bottle into sealing.
Embodiment 7
(1) gets the raw materials ready: take by weighing former, adjuvant by following weight;
Folium Ginkgo extract 40g
PEG400 277.5g
Medicinal alcohol 160g
Nectar source sugar 30g
Folium Ginkgo extract and adjuvant weight ratio are 1:11.7;
(2) PEG400, medicinal alcohol and nectar source sugar are mixed, stir, be prepared into mixed solution;
(3) when above-mentioned mixed solution is mixed to liquid level and does not have medicated powder, Folium Ginkgo extract is at the uniform velocity joined in the mixed solution of step (2) preparation, adopt the dissolving of stirring and dissolving method, mix homogeneously;
(4) amount of being adjusted to: add water and be adjusted to ormal weight 1000ml, make the ginkgo leaf extract drop medicinal liquid;
(5) packing: the medicine liquid irrigation that makes is packed in the bottle into sealing.
Embodiment 8
(1) gets the raw materials ready: take by weighing former, adjuvant by following weight;
Folium Ginkgo extract 40g
PEG400 277.5g
Medicinal alcohol 120g
Nectar source sugar 30g
Folium Ginkgo extract and adjuvant weight ratio are 1:10.7;
(2) PEG400, medicinal alcohol and nectar source sugar are mixed, stir, be prepared into mixed solution;
(3) when above-mentioned mixed solution is mixed to liquid level and does not have medicated powder, Folium Ginkgo extract is at the uniform velocity joined in the mixed solution of step (2) preparation, adopt the dissolving of stirring and dissolving method, mix homogeneously;
(4) amount of being adjusted to: add water and be adjusted to ormal weight 1000ml, make the ginkgo leaf extract drop medicinal liquid;
(5) packing: the medicine liquid irrigation that makes is packed in the bottle into sealing.
Embodiment 9
(1) gets the raw materials ready: take by weighing former, adjuvant by following weight;
Folium Ginkgo extract 40g
PEG400 388.5g
Medicinal alcohol 160g
Cyclamate 30g
Folium Ginkgo extract and adjuvant weight ratio are 1:14.5;
(2) PEG400, medicinal alcohol and cyclamate are mixed, stir, be prepared into mixed solution;
(3) when above-mentioned mixed solution is mixed to liquid level and does not have medicated powder, Folium Ginkgo extract is at the uniform velocity joined in the mixed solution of step (2) preparation, adopt the dissolving of stirring and dissolving method, mix homogeneously;
(4) amount of being adjusted to: add water and be adjusted to ormal weight 1000ml, make the ginkgo leaf extract drop medicinal liquid;
(5) packing: the medicine liquid irrigation that makes is packed in the bottle into sealing.
Embodiment 10
(1) gets the raw materials ready: take by weighing former, adjuvant by following weight;
Folium Ginkgo extract 40g
PEG400 444g
Medicinal alcohol 200g
Cyclamate 40g
Folium Ginkgo extract and adjuvant weight ratio are 1:17.1;
(2) PEG400, medicinal alcohol and cyclamate are mixed, stir, be prepared into mixed solution;
(3) when above-mentioned mixed solution is mixed to liquid level and does not have medicated powder, Folium Ginkgo extract is at the uniform velocity joined in the mixed solution of step (2) preparation, adopt the dissolving of ultrasonic dissolution method, mix homogeneously;
(4) amount of being adjusted to: add water and be adjusted to ormal weight 1000ml, make the ginkgo leaf extract drop medicinal liquid;
(5) packing: the medicine liquid irrigation that makes is packed in the bottle into sealing.
Embodiment 11
(1) gets the raw materials ready: take by weighing former, adjuvant by following weight;
Folium Ginkgo extract 40g
PEG400 111g
Medicinal alcohol 72g
Cyclamate 20g
Folium Ginkgo extract and adjuvant weight ratio are 1:5.1;
(2) PEG400, medicinal alcohol and cyclamate are mixed, stir, be prepared into mixed solution;
(3) when above-mentioned mixed solution is mixed to liquid level and does not have medicated powder, Folium Ginkgo extract is at the uniform velocity joined in the mixed solution of step (2) preparation, adopt the dissolving of stirring and dissolving method, mix homogeneously;
(4) amount of being adjusted to: add water and be adjusted to ormal weight 1000ml, make the ginkgo leaf extract drop medicinal liquid;
(5) packing: the medicine liquid irrigation that makes is packed in the bottle into sealing.
Embodiment 12
(1) gets the raw materials ready: take by weighing former, adjuvant by following weight;
Folium Ginkgo extract 40g
PEG400 666g
Propylene glycol 150g
Medicinal alcohol 160g
Cyclamate 30g
Folium Ginkgo extract and adjuvant weight ratio are 1:25.2;
(2) PEG400, medicinal alcohol, propylene glycol and cyclamate are mixed, stir, be prepared into mixed solution;
(3) when above-mentioned mixed solution is mixed to liquid level and does not have medicated powder, Folium Ginkgo extract is at the uniform velocity joined in the mixed solution of step (2) preparation, adopt the dissolving of stirring and dissolving method, mix homogeneously;
(4) amount of being adjusted to: add water and be adjusted to ormal weight 1000ml, make the ginkgo leaf extract drop medicinal liquid;
(5) packing: the medicine liquid irrigation that makes is packed in the bottle into sealing.
Every 1ml contains total flavonoids and all is no less than 9.6mg, contains the content sum of terpene lactone in bilobalide (C15H18O8), ginkalide A (C20H24O9), ginkalide B (C20H24O10), ginkalide C (C20H24O11) in the ginkgo leaf extract drop of above embodiment preparation, all is no less than 2.4mg.
The animal pharmacodynamic experiment of Folium Ginkgo drop of the present invention:
One, experiment summary: the Folium Ginkgo drop improves significantly to the animal brain ischemic injuries: in mice broken end cerebral ischemia test, compare with its excipient blank group, dosage with 5-10mg/kg (by the flavonoid glycoside cubage) drips clothes, is obviously prolonged (P<0.01) time of panting of animal; In acute cerebral ischemia in rats test, drip clothes with the dosage of 3-10mg/kg, with model group relatively, can obviously reduce the brain water content of cerebral ischemia animal.Animal anoxia, ischemic myocardial are had the certain protection effect: in rat heart muscle ischemia test, the Folium Ginkgo drop that gives 3mg/kg can obviously resist the myocardial ischemic injury due to the pituitrin; In mice normal pressure hypoxia endurance test, give the drop of 5-15mg/kg, the time-to-live of animal is obviously prolonged.And the Folium Ginkgo drop can make blood viscosity of blood stasis animal (rat) and platelet aggregation be able to obvious improvement.Various effects that the Folium Ginkgo drop is shown and Ginkgo oral liquid compare, and its intensity quite or slightly is better than the latter.
Folium Ginkgo drop (10mg/ml HPLC method) is a high-load flavonoid glycoside Folium Ginkgo extract product.Be the arteries dilator, be mainly used in activating blood circulation to dissipate blood stasis, TONGMAI SHULUO, the cerebral ischemia disease is had some improvement.And this dosage form oral dose is little, and facility is carried.This paper is with its existing dosage form---and ginkgo leaf extract oral liquid (10ml/ props up, 2.0mg/ml determined by ultraviolet spectrophotometry content) has carried out the research of part pharmacodynamic experiment to this dosage form (drop) in contrast.
Two, test method and result
1, cerebral ischemia test
1.1 influence to the time of breathing of dehiscing behind the mice broken end
1.1.1 material: select 72 of 17-20g healthy mices for use, ♂ ♀ half and half.
1.1.2 grouping: divide six groups at random; Three groups is the reagent group, the ginkgo leaf extract drop that splashes into three kinds of various dose respectively at the mice oral cavity is respectively heavy dose of group (containing Folium Ginkgo extract 15mg/kg), middle dosage group (containing Folium Ginkgo extract 5mg/kg), small dose group (containing Folium Ginkgo extract 1.67mg/kg), and the amount of splashing into is 15 μ l/10g (with the metering of mice body weight); Other establishes three matched groups, i.e. excipient blank group (consumption is with the reagent group), troxerutin positive drug control group (consumption is with the reagent group); The former drug form matched group of ginkgo leaf extract oral liquid (containing Folium Ginkgo extract 15mg/kg), consumption is 90 μ l/10g.
1.1.3 experimental technique: the oral cavity splashed into or irritated stomach once every day, continuous seven days, and after the last administration 1 hour, break end fast in the ear bottom with shears, breathe the persistent period behind the record broken end (second .S) is with T check carrying out statistical disposition.
1.1.4 experimental result and analysis:
Ginkgo leaf extract drop heavy dose, middle dosage and small dose group compare, P<0.05, P<0.01.
The ginkgo leaf extract drop of 5mg/kg and 15mg/kg is breathed the time after can obviously prolonging the mice broken end, compares with the blank group, learns by statistics and handles, and extremely significantly meaning is arranged.Its drug action intensity of ginkgo leaf extract drop of the present invention and troxerutin and ginkgo leaf extract oral liquid phase are worked as.Show from secular clinical experiment, the side effect of troxerutin is bigger and in rising trend year by year, from this experiment, dyspnea has wherein taken place even has stopped the welt sample erythema that differing in size appears in nape skin severe allergic reactions such as (pressing colour-fast) before the broken end after 2 medications in troxerutin group 9 mices.From consumption, ginkgo leaf extract drop of the present invention is compared with oral liquid, the drop of identical Folium Ginkgo extract concentration and oral liquid, and the consumption of drop will be far smaller than the consumption of oral liquid.
1.2 protective effect to the experimental rat cerebral ischemia
1.2.1 selection: select 105 of healthy ♂ rats for use, body weight 272 ± 27g.
1.2.2 grouping: divide equally seven groups at random; Dosage is standard with the rat body weight; The reagent group is selected the embodiment of the invention 4 respectively for use, 5, the ginkgo leaf extract drop of 6 preparations 1. sham operated rats (is explained: also undergo surgery, but do not carry out ligation and cause ischemia, directly stitching) 2. model control group (is explained: rat is undergone surgery sew up after ligation causes ischemia, bestow excipient, promptly do not add medicine and only add the control sample that adjuvant is made) the 3. 4. 5. 6. 7. former dosage form matched group of ginkgo leaf extract oral liquid (containing Folium Ginkgo extract 10.0mg/kg) of troxerutin positive drug control group of the heavy dose of reagent group of the present invention (containing Folium Ginkgo extract 10.0mg/kg) of dosage reagent group (containing Folium Ginkgo extract 3.0mg/kg) among the present invention of the low dose of reagent group of the present invention (containing Folium Ginkgo extract 1.0mg/kg).
1.2.3 experimental technique: at first make cerebral ischemic model, rat is undergone surgery sew up after ligation causes ischemia.The operation back regularly splashes into or irritates stomach once every day in the rat oral cavity, and continuous 10 days, behind the last medicine, underwent surgery in 1 hour, the ligation bilateral common carotid arteries was put to death after 3 hours, took out cerebral tissue and tested.The consumption of excipient, low dose of reagent group, middle dosage reagent group, heavy dose of reagent group and troxerutin is 15 μ l/10g, and ginkgo leaf extract oral liquid consumption is 90 μ l/10g.
Test index is: 1, cerebral index; 2, brain water content; 3, capillary permeability: promptly at ligation carotid artery preceding 5 minutes, i.v was soaked in respectively behind the decerebrate in the formamide solution according to train of thought orchid (EVB) 50mg/kg, 45 ℃ of incubations 72 hours.Use its immersion, carry out colorimetric, calculate EVB content in the brain at wavelength 630nm place.More than each index all carry out statistical procedures with t check.4, tissue morphology is observed.
1.2.4 experimental result and analysis:
Each index shows that cerebral ischemia has the certain protection effect to the rat imperfection for Folium Ginkgo drop 3mg/kg and 10mg/kg.EVB content and the apparent in view increase of sham operated rats in brain water content of model control group animal and the brain, statistical procedures have extremely significantly meaning (P<0.01); And except that Folium Ginkgo extract drop 1.0mg/kg group, EVB content all is starkly lower than model control group in the brain water content of other each medication treated animal and the brain, and statistical procedures has extremely significantly meaning (P<0.01); Observe by tectology, the rat tissue of cerebral ischemic model matched group and sham operated rats relatively have tangible pathological change.Sham operated rats rat tissue neurocyte and neurogliocyte are normal, i.e. kernel, and nuclear membrane is clear, and endochylema is bright, and blood capillary is with around little vessel lumen and neurocyte and the little blood vessel space being arranged all.The cerebral tissue neuronal shrinkage of model control group rat, cell space diminishes, the glial cell lucent area increases, neurocyte, blood capillary and little circumvascular space are obviously given wide, around the ventricles of the brain between matter loose, meningovascular, chamber film blood vessel blood stasis is obvious.And the dosage group is organized with heavy dose of in the ginkgo leaf extract drop, and brain tissue pathology change's degree of troxerutin group and ginkgo leaf extract oral liquid group rat all obviously is lighter than model control group.But brain tissue pathology change's degree of dosage group and heavy dose of group rat all obviously is lighter than troxerutin group and ginkgo leaf extract oral liquid group in the ginkgo leaf extract drop of the present invention.
2, myocardial ischemia, hypoxia test
2.1 to the influence of anoxia enduring time-to-live of mice normal pressure
2.1.1 selection: choose 90 of ♂ mices, body weight 18-22g.
2.1.2 grouping: divide equally six groups at random; Every group of consumption measures with the mice body weight.Remove except the Folium Ginkgo extract oral liquid group, other group consumptions are 15 μ l/10g, and ginkgo leaf extract oral liquid consumption is 90 μ l/10g.
Excipient blank group, Folium Ginkgo drop small dose group (containing Folium Ginkgo extract 1.67mg/kg), middle dosage group (containing Folium Ginkgo extract 5.0mg/kg), high dose group (containing Folium Ginkgo extract 15mg/kg) reagent group, propranolol positive drug control group and the former dosage form matched group of ginkgo leaf extract oral liquid (containing Folium Ginkgo extract 15mg/kg).Except that propranolol medication once (i.g), other each group all continuously the oral cavity splashed into or irritate stomach seven days, choose 72 of body weight 20-24g mices (12 every group) before the last medication and be used for test.After the last medication 40 minutes, it was that 250ml fills in the sealing ground wide mouthed bottle of 15g sodica calx that mice is placed capacity respectively, observed and recorded death time, t check carrying out statistical disposition.
2.1.3 result and analysis:
The Folium Ginkgo drop of middle dosage group (5mg/kg) and high dose group (15mg/kg) can obviously prolong the time-to-live of mice normal pressure anoxia enduring.Except that low dose, time-to-live of other each medication group mice and blank group more all have extremely significantly meaning (P<0.01).And as can be known, ginkgo leaf extract drop makes the prolongation effect of mice time-to-live be dose dependent.The action intensity of its 5.0mg/kg dosage is suitable with ginkgo leaf extract oral liquid 9ml/kg.Explanation will reach equal drug effect, and ginkgo leaf extract oral liquid using dosage is 6 times of Folium Ginkgo drop.
2.2 protective effect to the rat heart muscle ischemia
2.2.1 draw materials: get 48 of healthy ♂ rats, body weight 294 ± 73g.
2.2.2 grouping: divide five groups at random, every group of consumption measures with the mice body weight.Excipient blank group, ginkgo leaf extract drop 1.0mg/kg and 3.0mg/kg two reagent groups (explaining :) for containing Folium Ginkgo extract 1.0mg/kg and 3.0mg/kg, the former dosage form matched group of sorbitrate positive drug control group and Ginkgo oral liquid (containing Folium Ginkgo extract 3.0mg/kg).Remove except the Folium Ginkgo extract oral liquid group, other group consumptions are 15 μ l/10g, and ginkgo leaf extract oral liquid consumption is 60 μ l/10g.
2.2.3 experimental technique: except that sorbitrate was administered once, all continuous oral cavity of other each group splashed into or irritates stomach 10 days.Behind the last medicine 1 hour, the anesthesia of i.p urethane, it is fixing to face upward the position, regulate electrocardiogram sensitivity to 1mv=20mm, chart speed is 50mm/ second, after the record II lead electrocardiogram, Sublingual i.v pituitrin 0.5u/kg, injection speed is 10 seconds, after the injection immediately, 15 seconds, 30 seconds, 1 minute, 2 minutes, 5 minutes, 15 fens duplicate record electrocardiograms.Raise and the J point is raised several (mv) and second phase heart rate slack-off to be index, to carry out statistical procedures with first phase T ripple.
2.2.4 experimental result and analysis:
Ginkgo leaf extract drop can make various myocardial ischemia symptoms such as slowing down of the rising of J point that pituitrin causes and T ripple and heart rate obviously alleviate, relatively have significantly or utmost point significant difference (P<0.05 with the blank group, P<0.01), it slightly is better than ginkgo leaf extract oral liquid to the effect that resists myocardial ischemia, and does not have statistical significance.But reach equal drug effect, the using dosage of the Ginkgo oral liquid of same medicine concentration is 4 times of ginkgo leaf extract drop, illustrates that the bioavailability of ginkgo leaf extract drop is higher than oral liquid far away.
3, to the influence of blood stasis model rat blood rheological characteristic and platelet aggregation
3.1 draw materials: choose 45 of healthy ♂ rats, body weight 278 ± 46.2g.
3.2 grouping: divide equally five groups at random: excipient blank group; The blood stasis model matched group; Ginkgo leaf extract drop (containing Folium Ginkgo extract 3mg/kg) reagent group; The former drug form matched group of compound Salviae Miltiorrhizae positive drug control group and ginkgo leaf extract oral liquid (containing Folium Ginkgo extract 3mg/kg).Remove except the Folium Ginkgo extract oral liquid group, other group consumptions are 15 μ l/10g, and ginkgo leaf extract oral liquid consumption is 90 μ l/10g (all by the rat body weight meterings).
3.3 experimental technique: the above oral cavity of respectively organizing respectively splashes into or irritates stomach and gives corresponding medicine and excipient, continuous 10 days.In the 10th day subcutaneous injection epinephrine (Adr) 0.08ml/100g, after 2 hours, rat was immersed in the frozen water 5 minutes, at 2 hours at interval, duplicate injection Adr stopped eating, in next day heart extracting blood carry out blood viscosity and platelet aggregation is measured.
3.4 influence to hemorheological property
Carrying out blood viscosity with capillary tube method measures: a. from well add about 2ml to four red light of normal saline (NS) all bright till, b. write down first, the blanking time that two red lights extinguish, high value of cutting as NS, same record the 3rd, low value of cutting of blanking time that the quatre lamp extinguishes such as NS, the c. taking heparin is prevented blood coagulation 2ml, till adding well to four red light is all bright; D. repeat the high value of cutting and the low value of cutting that the b step gets whole blood; E. institute is surveyed the NS value and remove the whole blood value then for terminating really.
Packed cell volume (HCT): whole blood is mixed injects in erythrocyte (RBC) the hematocrit pipe, with 3000rpm centrifugal 30 minutes, observe RBC hematocrit pipe scale, HTC.
Carry out fibrinogen assay with biuret method.
The result shows: the ginkgo leaf extract drop of 3mg/kg has tangible mitigation to the rat acute blood stasis, and its intensity and ginkgo leaf extract oral liquid phase are worked as, and ginkgo leaf extract drop can reach same drug effect with the dosage that is far smaller than Ginkgo oral liquid as can be seen.
3.5 influence to the platelet focusing function
Get the 40ml blood sample, 3.8% sodium citrate anti-condensation (9:1 V/V) is put in the silication pipe, 800rpm * 5 are minute centrifugal, collect upper strata platelet rich plasma (PRP), and surplus blood 3000rpm * 5 minutes is centrifugal, collect platelet poor plasma (PPP), counting PRP causes 250,000/mm3 with the PPP adjustment, gets 225 μ lPRP and PPP respectively, use the PRP zeroising, PPP transfers " 100 ", adds 5 minutes platelet aggregation situations of 25 μ l derivants (ADP, final concentration 23.4um) record then in the PRP pipe.
The result:
Ginkgo leaf extract drop has tangible reduction effect and effect to be better than ginkgo leaf extract oral liquid to the platelet aggregation rate of stasis syndrome rat model.
Three, the animal pharmacodynamics experimental summary of Folium Ginkgo drop of the present invention:
Folium Ginkgo drop (10mg/ml HPLC method) is a high-load flavonoid glycoside Folium Ginkgo extract product.The dosage form oral dose of making is little, and facility is carried.This paper is with its existing dosage form---and ginkgo leaf extract oral liquid (10ml/ props up, 2.0mg/ml determined by ultraviolet spectrophotometry content) has carried out the research of part pharmacodynamic experiment to this dosage form (drop) in contrast.
1,1. Folium Ginkgo drop medication 0.15mg/10g is tested in cerebral ischemia, positive drug control group troxerutin medication 2mg/10g, and ginkgo leaf extract oral liquid medication 0.18mg/10g, the time of breathing can obviously prolong to dehiscing behind the mice broken end; And from dosage, the consumption of ginkgo leaf extract drop of the present invention will be far smaller than the consumption of troxerutin; The consumption of ginkgo leaf extract oral liquid is obviously more than the consumption of ginkgo leaf extract drop of the present invention.2. each index shows Folium Ginkgo drop 3-10mg/kg, and cerebral ischemia has the certain protection effect to the rat imperfection, and EVB content obviously reduces in the brain water content of rats with cerebral ischemia and the brain; And dosage group (3mg/kg) and heavy dose of group (10mg/kg) in the ginkgo leaf extract drop, brain tissue pathology change's degree that troxerutin (100mg/kg) and Ginkgo oral liquid (12mg/kg) are organized rat all obviously is lighter than model control group.
2, myocardial ischemia, 1. hypoxia test shows the test of mice normal pressure anoxia enduring time-to-live: the Folium Ginkgo drop of middle dosage group (5mg/kg) and high dose group (15mg/kg) can obviously prolong the time-to-live of mice normal pressure anoxia enduring, and as can be known, ginkgo leaf extract drop makes the prolongation effect of mice time-to-live be dose dependent, and the action intensity of its 5.0mg/kg dosage and ginkgo leaf extract oral liquid 18mg/kg dosage (9ml/kg) are suitable.Explanation will reach equal drug effect, and ginkgo leaf extract oral liquid using dosage is 3.6 times of Folium Ginkgo drop.2. the protective effect test to the rat heart muscle ischemia shows: ginkgo leaf extract drop 1.0mg/kg and 3.0mg/kg two reagent groups; various myocardial ischemia symptoms such as slowing down of the rising of J point that pituitrin causes and T ripple and heart rate are obviously alleviated, and it slightly is better than 12mg/kg Ginkgo oral liquid matched group to the effect that resists myocardial ischemia.And the dosage of Ginkgo oral liquid is 4 times of ginkgo leaf extract drop.
3, the test to blood stasis model rat blood rheological characteristic and platelet aggregation shows: ginkgo leaf extract drop has tangible reduction effect to the platelet aggregation rate of stasis syndrome rat model; The ginkgo leaf extract drop of 3mg/kg has tangible mitigation to the rat acute blood stasis, and the ginkgo leaf extract oral liquid phase of its intensity and 12mg/kg is worked as, and ginkgo leaf extract drop can reach same drug effect with the dosage that is far smaller than Ginkgo oral liquid as can be seen.
The research of ginkgo leaf extract drop acute toxicity testing
One, experiment summary: ginkgo leaf extract drop is carried out acute toxicity testing with mice, calculate by contained flavonoid glycoside amount, its median lethal dose(LD 50) (LD50) is 521.86mg/kg (95% fiducial limit: 502.67-541.80mg/kg), be equivalent to crude drug amount 100g/kg approximately, be 869 times of clinical people's consumption.
Two, experiment brief summary:
Acute toxicity testing shows: ginkgo leaf extract drop is 521.87mg/kg (502.67-541.80mg/kg) to the LD50 that irritates stomach, is equivalent to crude drug amount 100g/kg approximately.Be 869 times of clinical consumptions, tolerance people consumption is oral more than 100 times, illustrates that the Folium Ginkgo drop has very high safety.
The research of ginkgo leaf extract drop rat long term toxicity
One, experiment summary: Folium Ginkgo according to the clinical consumption and the course of treatment, carried out the i.g administration 90 days to ginkgo leaf extract drop, the rat long term toxicity test of 15 days convalescent periods for the medicine of the treatment heart, cerebrovascular disease.Be divided into ginkgo leaf extract drop height (5ml/kg/d, 104 times of clinical consumptions), low (1.5ml/kg/d) two dosage groups, excipient group and blank group.The result: each treated animal generally shows, and indexs such as body weight, routine blood test regulating liver-QI, renal function biochemistry detection learn to be handled by statistics, does not all have significant difference (P〉0.05).When pathological examination found that medication finishes, inflammation was obvious in the heavy dose of group of the ginkgo leaf extract drop part animal hilus renalis district after birth, and convalescent period shows no obvious abnormalities when finishing.Show: rat i.g1.5ml/kg/d is safer.
Two, experiment brief summary:
Ginkgo leaf extract drop in the dosage range of 1.5-5ml/kg/d, i.g90 days continuously, in the rat long term toxicity test of 15 days convalescent periods, with matched group relatively, the diet of animal, activity and body weight gain situation are normal substantially, do not have dead the generation; Hematology and blood biochemical are learned each index and are not also seen harmful effect; The main organs coefficient no significant difference of each treated animal, not seeing morphological change, pathologic finding, when finding that medication finishes, the Folium Ginkgo high dose group, part animal hilus renalis district chronic inflammation cellular infiltration, convalescent period is when finishing, no abnormality seen.Show: the safe dose of the long poison of ginkgo leaf extract drop rat is 1.5ml/kg/d (is about clinical consumption 30 times).
Folium ginkgo dripping pill and drop production technology, equipment cost are relatively
One, folium ginkgo dripping pill production technology, equipment:
1, Folium Ginkgo extract raw material and substrate adjuvant join in the mixer, and heated and stirred is mixed and made into admixing medical solutions.
2, admixing medical solutions is transported in the fluid reservoir of drop pill machine, drips the system drop pill.
3, the drop pill of making is transported in the centrifuge, gets rid of cold oil on the most drop pill.
4, drop pill is transported to pill-screening machine top sieve ball, sorts out piller, broken ball, sticking ball.
5, packing, labeling.
Two, Folium Ginkgo drop production technology, equipment:
1, with diluent, cosolvent, sedan-chair flavor agent adjuvant, joins in the Agitation Tank, stir and make mixed solution.
2, the Folium Ginkgo extract raw material is at the uniform velocity joined in the mixed solution, adopt the dissolving of stirring and dissolving method, mix homogeneously.
3, Jia Shui is adjusted to ormal weight, makes the ginkgo leaf extract drop medicinal liquid.
4, packing, labeling.
Three, the two compares
1, the drop pill production technology is seen, drop pill is produced equipment needed thereby before the packing: drop pill machine, centrifuge, pill-screening machine; Do not comprise mixer, a medium-sized production-scale cover drop pill production equipment needs 270,000 yuan of funds (the piller drilling pill device that every ball 70mg is following is if the above drilling pill device of every ball 70mg then needs 500,000 yuan of funds).The drop production technology is seen, drop production equipment before the packing: the Agitation Tank that only needs the band stirring; Production-scale production equipment, the fund of need gets final product for several ten thousand yuan.Find out that thus the infusion of financial resources of drop equipment is less than drilling pill device far away.
See by production process that 2, the drop production technology is simple, get final product packing after the dosing; Drop pill then needs a few step production technologies, and the production cost drop cost height that compares is more.
3, finished product relatively: compare by above-mentioned production technology and equipment, calculate that drop pill finished product production cost is more than 2 times of drop finished product at least.
As from the foregoing, Folium Ginkgo extract drop pill product cost is too high, and ordinary consumer is difficult to bear economically, and consumer groups only limit to economy preferably.The good drug efficacy of Folium Ginkgo drop, cost is low, moderate cost, ordinary consumer all can be accepted, and suitable consumption patient is in extensive range.
Claims (10)
1, a kind of ginkgo leaf extract drop is characterized in that, its active constituents of medicine is a Folium Ginkgo extract, and the weight ratio of Folium Ginkgo extract and other adjuvants is 1:5~1:25.5; It specifically is to be made by the Folium Ginkgo extract of following weight portion proportioning and adjuvant:
1 part of Folium Ginkgo extract;
Adjuvant: 2~25 parts of diluent; 1~20 part of cosolvent; 0.01~2 part of correctives.
2, a kind of ginkgo leaf extract drop according to claim 1 is characterized in that, described diluent is one or more in propylene glycol, glycerol, the PEG400.
3, a kind of ginkgo leaf extract drop according to claim 1 and 2 is characterized in that, diluent concentration is 20~90% in the described drop.
4, a kind of ginkgo leaf extract drop according to claim 1 is characterized in that, described cosolvent is one or more in medicinal alcohol, glycerol, the PEG400.
5, according to claim 1 or 4 described a kind of ginkgo leaf extract drops, it is characterized in that cosolvent concentration is 10~80% in the described drop.
6, a kind of ginkgo leaf extract drop according to claim 1 is characterized in that, described correctives is a kind of in protein sugar, nectar source sugar, the sweet close element.
7, according to claim 1 or 6 described a kind of ginkgo leaf extract drops, it is characterized in that correctives concentration is 0.01~5% in the described drop.
8, a kind of ginkgo leaf extract drop according to claim 1 is characterized in that, described Folium Ginkgo extract is 100~200 order spray drying fine powders, contains moisture less than 3%.
9, a kind of preparation method of ginkgo leaf extract drop is characterized in that, it comprises the following steps:
(1) gets the raw materials ready: take by weighing Folium Ginkgo extract and each adjuvant by the described weight portion of claim 1;
(2) cosolvent, an amount of diluent, the agent of sedan-chair flavor are mixed, stir and make mixed solution;
(3) when above-mentioned mixed solution is mixed to liquid level and does not have medicated powder, Folium Ginkgo extract is at the uniform velocity added dissolving and mix homogeneously;
(4) amount of being adjusted to: add water and be adjusted to ormal weight, promptly make the ginkgo leaf extract drop medicinal liquid.
10, the preparation method of a kind of ginkgo leaf extract drop according to claim 9 is characterized in that, ultrasonic dissolution method, heating for dissolving method or stirring and dissolving method are adopted in dissolving in the described step (3), and the temperature of described heating for dissolving is 40~50 ℃.
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CN102309054A (en) * | 2011-08-11 | 2012-01-11 | 青岛三九九洲生物技术有限公司 | Ginkgo biloba essence oral liquid, preparation method thereof and application thereof |
CN103877130A (en) * | 2013-09-17 | 2014-06-25 | 狄留庆 | Chinese medicinal composition for treating ischemic cerebral paralysis, application thereof to preparation of oral preparation and preparation of Chinese medicinal composition |
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CN102309054A (en) * | 2011-08-11 | 2012-01-11 | 青岛三九九洲生物技术有限公司 | Ginkgo biloba essence oral liquid, preparation method thereof and application thereof |
CN102309054B (en) * | 2011-08-11 | 2014-04-02 | 青岛三九九洲生物技术有限公司 | Ginkgo biloba essence oral liquid, preparation method thereof and application thereof |
CN103877130A (en) * | 2013-09-17 | 2014-06-25 | 狄留庆 | Chinese medicinal composition for treating ischemic cerebral paralysis, application thereof to preparation of oral preparation and preparation of Chinese medicinal composition |
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