CN100352455C - Ginkgo Damo freeze-drying prepn. and its prepn. method - Google Patents
Ginkgo Damo freeze-drying prepn. and its prepn. method Download PDFInfo
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- CN100352455C CN100352455C CNB2005102006785A CN200510200678A CN100352455C CN 100352455 C CN100352455 C CN 100352455C CN B2005102006785 A CNB2005102006785 A CN B2005102006785A CN 200510200678 A CN200510200678 A CN 200510200678A CN 100352455 C CN100352455 C CN 100352455C
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Abstract
The present invention provides a ginkgodamo freeze-drying preparation and a preparation method thereof, which is prepared with ginkgo leaf extract and dipyridamole according to the calculation of weight components. Compared with the prior art, the method of the present invention can scientifically and reasonably guide production and solve the difficult technical problems of poor medicine stability of the present invention, difficult mold of the freeze-drying preparation and bad solubility; no supplementary material is added in the preparation of the present invention, so the adverse reaction of supplementary materials on human bodies is avoided, the contents of effective ingredients in medicine can be increased, and the medicine effect can be enhanced.
Description
Technical field: the present invention relates to a kind of ginkgo Damo freeze-drying preparation and preparation method thereof, belong to the field of medicine technology.
Technical background: the harm that diseases of cardiovascular and cerebrovascular systems causes the mankind has made its mortality rate be in first.Though have many medicines to put goods on the market at present, with regard to general status, the medicine that domestic pharmaceutical factory produces is dull mostly aging, though that joint medicine, imported medicine show in this respect is original, price is higher, and patient is difficult to accept.Through a large amount of clinical trials, prove that this product can effectively adjust antiotasis by " Ginkgo Leaf Extract and Dipyridamole Injection " of the applicant development, remove free radical, improve hemorheology, the antagonism platelet activating factor alleviates neuronal damage, is the good medicine of treatment cardiovascular and cerebrovascular disease.But this product exists dipyridamole not good shortcoming of stability in preparation, problems such as difficult forming or dissolubility be not good also can appear in the process of preparation lyophilized powder simultaneously, so usually adding various adjuvants, most of producers overcome the above problems, the Dongfang Tianxiang Medical Technology Development Co., Ltd., Beijing applied for patent " injection freeze-dried composition " as on January 14th, 2003, the patent No. is: 03104645.2, in order to solve solubility problem, in medicine, used surfactant in this patent; On June 23rd, 2004, Hubei Hope Pharmaceutical Co., Ltd. applied for a patent " ginkgo bilobate extract injectable powder and preparation method ", and number of patent application is: 200410043336.8, used beta-cyclodextrin derivative in order to solve solubility problem in this patent; Jiang Weishi application on February 11 in 2004 patent " ginkgo-dipyridamole for injection and preparation technology thereof ", number of patent application is: 200410013547.1, used excipient such as mannitol for the problem that solves the preparations shaping difficulty in this patent; Though problems such as above adjuvant has solved this formed product difficulty, dissolubility is not good or dipyridamole stability is bad owing to contain adjuvant in the medicine, make that active constituent content reduces in the medicine, and the adjuvant that adds also can produce untoward reaction to human body; In patent application 200410013547.1, pH value is 2.5-7.5 in addition, because this pH value scope is bigger, this pharmaceutical preparation does not reach the best stabilized effect.
Summary of the invention: the objective of the invention is to: a kind of ginkgo Damo freeze-drying preparation and preparation method thereof is provided, this method can be scientific and reasonable guidance production, solve that stability of drug products of the present invention is not good, lyophilized formulations difficult forming, the bad technical barrier of dissolubility; And do not add any adjuvant in the preparation of the present invention, can avoid adjuvant to the untoward reaction that human body produces, make active constituent content increase in the medicine, its drug effect strengthens.
The present invention constitutes like this: calculate according to composition by weight: it is made in total flavonoids 1-10 part and dipyridamole 0.5-5 part by Folium Ginkgo extract.
The preparation method of ginkgo Damo freeze-drying preparation is: dipyridamole is mixed with Folium Ginkgo extract and be dissolved in the water for injection, regulate PH to 2.5-5, add the injection water to 1000-4000ml, filter, be filled into cillin bottle, lyophilizing, roll behind the lid promptly.
Concrete preparation method is: take by weighing dipyridamole, add 20-100 and doubly measure in the water for injection, regulate PH3～6 with dilute hydrochloric acid, dipyridamole is dissolved fully; Take by weighing Folium Ginkgo extract, add 20-100 and doubly measure in the water for injection; With the solution and the dipyridamole solution mixing of Folium Ginkgo extract, add the injection water to 1000-4000ml, regulate PH2.5～5, mixing filters through the filter membrane smaller or equal to 0.45 μ m, is filled into cillin bottle by every 1-5ml, lyophilizing, rolls behind the lid promptly.
Freeze-drying process in the above-mentioned preparation method is: send into freeze dryer after cillin bottle half tamponade that fill is good, slowly be refrigerated to below-20 ℃, be evacuated to 5-35Pa, control heat temperature raising speed is no more than 3 ℃/h and distils, after distillation 10-30 hour, setting shelf temperature and be 20-40 ℃, to carry out second time dry, when products temperature and shelf temperature near the time, steady temperature drying total head plug after 2-5 hour.
The present invention is directed in the existing ginkgo Damo freeze-drying powder and all add adjuvant, and the adjuvant that adds makes the shortcoming that active constituent content reduces in the medicine, does not add any adjuvant in preparation of the present invention.We find in product research, and poorly soluble in water of the dipyridamole in " Ginkgo Leaf Extract and Dipyridamole Injection " made behind the product easily oxidizedly again, is the main cause that causes dipyridamole stability bad.The inquiry data as can be known, dipyridamole is easily molten in diluted acid, unstable under strong acidic condition, the pH value scope of dipyridamole injection liquid is 2.5-4.5 in the Pharmacopoeia of the People's Republic of China, but in this preparation, the medicine pH value not only will guarantee the stability of dipyridamole, also will guarantee the stability of effective ingredient in the Folium Ginkgo extract, also to guarantee the clarity of medicinal liquid simultaneously, and cause stimulating human body to be advisable when being unlikely to infuse again.The pH value scope is bigger in the patent application 200410013547.1, pharmaceutical preparation does not reach the best stabilized effect, we discover, when this preparation of Chinese medicine pH value is controlled at 2.5-5, the stability of dipyridamole and Ginkgo total flavones alcohol glycosides can reach best, and filter back medicinal liquid clarification, do not have insoluble microgranule, stable performance, the zest that also can avoid the infusion process Chinese medicine that human body is produced.Find after deliberation that in addition parameter control also is the main cause that influences this lyophilized formulations mouldability, dissolubility and preparation stability in the freeze-drying process.If adopt lyophilizing parameter of the present invention, control the pH value in the medicinal liquid simultaneously, can under the situation of not using adjuvant, guarantee mouldability, dissolubility and the preparation stability of this preparation.And we discover, the ginkgo Damo freeze-drying powder that does not add adjuvant and the product that adds adjuvant relatively, there are no significant difference such as goods character, dissolubility, stability, but that the curative effect of medication under the same dosage will be good is many.
In this preparation, the lyophilized powder loading amount is that 10-50mg/ props up, wherein every to contain dipyridamole be 1-5mg, total flavonoids is 2-10mg; The terpenoid lactone is 0.5-3mg.
In more than forming, every part of representative be weight portion.Weight is calculated with crude drug, and as if being unit with the gram, more than composition can be made into freeze-dried powder 500-2000 and props up every dress 5mg-50mg.
Compared with prior art, the guidance production that the inventive method not only can be scientific and reasonable solves that stability of drug products of the present invention is not good, lyophilized formulations difficult forming, the bad technical barrier of dissolubility; And do not add any adjuvant in the preparation of the present invention, the untoward reaction of having avoided adjuvant that human body is produced.Simultaneously, owing to do not add any adjuvant in the medicine, active constituent content increases in the medicine, and its drug effect strengthens, and the effect of treatment cardiovascular and cerebrovascular disease is apparent in view.
Experimental example:
One, the medicinal liquid pH value directly has influence on the quality of medicine, should guarantee the stability of active ingredient, causes stimulating human body when being unlikely to infuse again.By the described method preparating liquid of invention, the results are shown in following table.
| Group | Medicinal liquid pH | Medicinal liquid clarity | Filter the back clarity | Dipyridamole content (mg/ml) | Loss rate (%) | Total flavonoids content (mg/ml) | Loss rate (%) |
| 1 | 1.48 | Muddy | Qualified | 0.9012 | 9.88 | 2.6154 | 4.89 |
| 2 | 2.51 | Muddy | Qualified | 0.9614 | 3.86 | 2.6384 | 4.05 |
| 3 | 3.25 | Muddy | Qualified | 0.9826 | 1.74 | 2.6090 | 5.12 |
| 4 | 5.05 | Muddy | Qualified | 0.9598 | 4.02 | 2.5978 | 5.53 |
| 5 | 6.54 | Muddy | A small amount of float is arranged after the filtration | 0.8528 | 14.72 | 2.3345 | 15.11 |
As seen from the experiment, between PH2.5～5, the loss rate minimum of dipyridamole and Ginkgo total flavones alcohol glycosides in the medicinal liquid, and filter the back medicinal liquid and clarify, do not have insoluble microgranule, so medicinal liquid PH is controlled at 2.5～5, can keep the stability of effective ingredient in the medicine.
Two, freeze-drying process is the maximum difficult point that the present invention makes freeze-dried products, and freeze-dry process directly has influence on the quality of freeze-dried products, and lyophilizing mainly is divided into prefreezing, sublimation drying, parsing-desiccation three parts.
1, adopts the method for freezing slowly during prefreezing of the present invention.Because find in experiment, the present invention adopts quick freezing, and when promptly per minute was more than 5 ℃, its distillation required time was less, but the product serious cracking, molding is poor; Slowly freeze method as adopting, control cooling rate per minute is below 5 ℃ the time, and the products appearance molding is good, so adopt the method for freezing slowly during prefreezing of the present invention.
2, should be refrigerated to below-20 ℃ during prefreezing, because the prefreezing temperature is below-20 ℃ the time, the Free water in the solution just can all be solidified.
3, the vacuum during evacuation is 5-35Pa.If vacuum is when 5pa is following, heat-transfer effect is relatively poor, and product is difficult for obtaining heat, and the distillation time then prolongs, and when distillation the product molding situation general; If vacuum is when 35pa is above, goods absorb can not in time to distil behind the heat to be removed moisture and causes product Hui Rong, and product molding is bad; In the time of between 5-35Pa, formed product is intact, and no Hui Rong and atrophy phenomenon produce, and required time is shorter.So control vacuum is advisable between 5pa～35pa during distillation.
4, during sublimation drying, programming rate is no more than 3 ℃/h, because if sublimation temperature surpasses 3 ℃/h, then goods have and dissolve phenomenon, are advisable so programming rate should be no more than 3 ℃/h.
If 5 distillation times, then the bound water in the goods can not be removed less than 10 hours, do not reach exsiccant purpose.If the distillation time is higher than 30 hours, drying time is long, and goods easily dissolve.So the distillation time is 10-30 hour, can remove the bound water in the goods, can guarantee that again goods are insoluble.
6, the parsing-desiccation temperature is 20-40 ℃, dry 2-5 hour, can remove the residual moisture in the goods, reaches the bin stability that improves product, prolongs the purpose of its storage life.
Three, stability test research of the present invention
1, light durability test and result
Get lyophilized formulations of the present invention, remove packing, be placed in the plate, (illumination: 3000lx), Continuous irradiation 10 days respectively at sampling in 5,10 days, is checked its appearance character, content, the results are shown in following table to place the clarity test device.
The light durability result of the test
| Time | Outward appearance | Dipyridamole content (mg/ props up) | Terpene lactone contents (mg/ props up) | Total flavonoids content (mg/ props up) |
| 0 day 5 days 10 days | The yellow loose shape thing of the yellow loose shape thing of yellow loose shape thing | 2.1 1.9 1.9 | 1.3 1.3 1.2 | 5.08 5.06 5.03 |
As seen, under high light 3000Lx condition, observed 10 days, active constituent content no significant difference in the preparation of the present invention, each detects index all in acceptability limit.
2, thimble test and result
Get lyophilized formulations of the present invention, put in 60 ℃ the calorstat ten days,, check its appearance character, content, the results are shown in following table respectively at sampling in 5,10 days.
Thimble test result
| Time | Outward appearance | Dipyridamole content (mg/ props up) | Terpene lactone contents (mg/ props up) | Total flavonoids content (mg/ props up) |
| 0 day 5 days 10 days | The yellow loose shape thing of the yellow loose shape thing of yellow loose shape thing | 2.1 2.2 2.0 | 1.3 1.3 1.2 | 5.08 5.09 5.06 |
As seen, under hot conditions, observed 10 days, active constituent content no significant difference in the preparation of the present invention, each detects index does not all have significant change.
3, high humidity stability test and result
Get lyophilized formulations of the present invention, be put in the surface plate, put in the constant humidity sealed container, placed 10 days under respectively at relative humidity 75 ± 5% conditions at 25 ℃, sampling is investigated in the time of the 5th, 10 day, checks its appearance character, content, the results are shown in following table.
High humidity stability test result
| Time | Outward appearance | Dipyridamole content (mg/ props up) | Terpene lactone contents (mg/ props up) | Total flavonoids content (mg/ props up) |
| 0 day 5 days 10 days | The yellow loose shape thing of the yellow loose shape thing of yellow loose shape thing | 2.1 2.2 2.0 | 1.3 1.4 1.3 | 5.08 5.07 5.09 |
As seen, under relative humidity 75% condition, observe 10 big, active constituent content no significant difference in the preparation of the present invention, each detects index does not all have significant change.
Four, preparation pharmacodynamic study of the present invention
(1) preparation of the present invention is to cat myocardial ischemia hemodynamics and Electrocardiographic influence
1, experiment medicine: preparation 1: according to the described method preparation of number of patent application 200410013547.1 " ginkgo-dipyridamole for injection and preparation thereof " technology; Preparation 2: according to the described method preparation of number of patent application 200410013336.8 " ginkgo bilobate extract injectable powder and preparation method "; Preparation 3: according to the described method preparation of number of patent application 03104645.2 " injection freeze-dried composition "; Preparation group of the present invention: prepare according to the method for the invention.
2, method and result: the animal random packet, respectively, intravenous administration.Animal is adopted tracheal intubation with pentobarbital sodium 30mg/kg intraperitoneal injection of anesthesia, connects the SC-2 respirator and practices artificial respiration.The 4th intercostal is opened breast, cut off pericardium, 1/3 intersection ligation down in left anterior descending branch, record II leads electrocardiogram, and thought-read electrograph S-T section and T ripple change, the animal random packet, intravenous injection gives medicine 5mg/kg before the ligation, give in the 1min, and the slow again drug administration by injection thing half of 1h is measured after ligation, annotated in the 5min, observed the every index of ligation 3h and change.The results are shown in following table:
Table 1 preparation of the present invention is to the influence of cat myocardial ischemia blood pressure
| Index | Group | Before the ligation | After the ligation | |||
| 15min | 60min | 120min | 180min | |||
| SBP | Normal saline | 158±21 | 132±21* | 130±28* | 122±28** | 117±27** |
| DBP | 112±26 | 93±14* | 90±23* | 80±28** | 69±28** | |
| SBP | Preparation 1 | 147±24 | 132±25 | 130±38 | 128±27* | 122±27* |
| DBP | 104±29 | 98±35 | 100±41 | 95±37 | 93±28* | |
| SBP | Preparation 2 | 131±18 | 128±28 | 120±28 | 114±49 | 107±30* |
| DBP | 97±27 | 91±29 | 89±29 | 85±27 | 78±42* | |
| SBP | Preparation 3 | 132±30 | 125±17 | 118±31 | 108±38* | 98±18* |
| DBP | 96±34 | 90±28 | 88±41 | 80±19 | 76±17* | |
| SBP | Of the present invention group | 136±28 | 130±20 | 133±21 | 131±19 | 131±27 |
| DBP | 97±20 | 95±20 | 93±27 | 92±18 | 91±17 | |
With comparison before the ligation, * P＜0.05; * P＜0.01
Table 2 preparation of the present invention is to cat myocardial ischemia heart rate, kinemic influence
| Index | Group | Before the ligation | After the ligation | |||
| 15min | 60min | 120min | 180min | |||
| Heart rate | The normal saline group | 158±14 | 150±18 | 142±17* | 137±16** | 120±14** |
| Preparation 1 | 163±12 | 161±19 | 150±27 | 141±13* | 142±28* | |
| Preparation 2 | 175±19 | 165±28 | 151±18 | 143±17* | 140±24* | |
| Preparation 3 | 136±18 | 121±15 | 109±24 | 100±21* | 92±18* | |
| Of the present invention group | 154±15 | 158±21 | 150±20 | 149±17 | 147±20 | |
| Cardiac output | The normal saline group | 196±56 | 180±74 | 154±69* | 137±68* | 126±46** |
| Preparation 1 | 199±27 | 180±34 | 159±52 | 157±47* | 141±64* | |
| Preparation 2 | 286±34 | 251±47 | 241±41 | 237±54* | 229±47* | |
| Preparation 3 | 262±48 | 237±48 | 229±57 | 209±57* | 212±57* | |
| Of the present invention group | 179±46 | 173±42 | 162±48 | 159±48 | 155±48 | |
With comparison before the ligation, * P＜0.05; * P＜0.01
Table 3 preparation of the present invention is to the influence of cat myocardial ischemia left indoor pressure (LVP), left ventricular end diastolic presssure (LVEDP)
| Index | Group | Before the ligation | After the ligation | |||
| 15min | 60min | 120min | 180min | |||
| LVP | The normal saline group | 154±46 | 125±37* | 119±35* | 104±29* | 97±31** |
| Preparation 1 | 156±45 | 147±38 | 140±35 | 137±28 | 134±65* | |
| Preparation 2 | 153±41 | 143±39 | 137±31 | 130±24* | 124±37* | |
| Preparation 3 | 133±56 | 128±51 | 124±47 | 119±32* | 106±28* | |
| Of the present invention group | 144±45 | 134±31 | 130±54 | 136±64 | 128±4 | |
| LVEDP | The normal saline group | 1±5 | 1±4 | 0±4 | -1±2 | -1±5 |
| Preparation 1 | -6±2 | -6±5 | -6±5 | -7±3 | -7±6 | |
| Preparation 2 | -5±5 | -5±4 | -5±2 | -6±2 | -5±2 | |
| Preparation 3 | -1±3 | 0±2 | 0±5 | -1±4 | -1±4 | |
| Of the present invention group | -2±4 | -2±5 | -2±7 | -2±3 | -3±4 | |
With comparison before the ligation, * P＜0.05; * P＜0.01
Table 4 preparation of the present invention is to the influence of the maximum rate of change of left ventricular pressure
| Index | Group | Before the ligation | After the ligation | |||
| 15min | 60min | 120min | 180min | |||
| dp/dt max | The normal saline group | 2720± 1006 | 2180± 760* | 1760±744* | 1840±836** | 1240± 783** |
| Preparation 1 | 2720±765 | 2260±835 | 1920±769 | 1700±607* | 1580±563* | |
| Preparation 2 | 3100±329 | 2860±316 | 2450±425 | 2010±550 | 1850±434* | |
| Preparation 3 | 2500±510 | 1970±701 | 1760±369 | 1459±512* | 1320±843* | |
| Of the present invention group | 2500±725 | 2383±261 | 2233±381 | 2300±564 | 2279±520 | |
| -dp/dt max | The normal saline group | 1860±359 | 1358±290 | 1320±318** | 1270±410** | 1130± 568** |
| Preparation 1 | 1890±540 | 1540±432 | 1460±452 | 1390±956 | 1260±621* | |
| Preparation 2 | 1750±572 | 1480±456 | 1460±562 | 1290±485 | 1183±456* | |
| Preparation 3 | 1640±927 | 1530±346 | 1309±379 | 1210±504* | 1060±891* | |
| Of the present invention group | 1720±765 | 1640±923 | 1560±460 | 1542±562 | 1520±614 | |
With comparison before the ligation, * P＜0.05; * P＜0.01
(2) preparation of the present invention is to the influence of cat ischemic myocardium infarction size
Behind the cat coronary ligation 3h, take off heart, dye, measure and calculate the infarction size of ischemic myocardium with the cardiac muscle section and with the nitroso-group tetrazole is blue.Experimental result sees Table 5.
Table 5 Ginkgo Leaf Extract and Dipyridamole Injection is to the influence of cat ischemic myocardium infarction size
| Group | Cat (only) | Dosage (mg/kg) | Infarction size (%) | The P value |
| The normal saline group | 5 | - | 36±7 | |
| Preparation 1 | 5 | 5 | 26±3 | ＜0.05 |
| Preparation 2 | 5 | 5 | 27±5 | ＜0.05 |
| Preparation 3 | 5 | 5 | 24±8 | ＜0.05 |
| Of the present invention group | 5 | 5 | 16±6 | ＜0.01 |
(3) conclusion: behind the normal saline group cat cardiac muscle coronary ligation, blood pressure, left indoor pressure, the maximum rate of change of left ventricular pressure, cardiac output etc. obviously reduce, the displacement of electrocardiogram S-T section, the T wave height is alarmmed, be myocardial ischemia, myocardial contractility is subjected to the obviously variation of influence, and administration group of the present invention is not seen significant change, and preparation 1, preparation 2, preparation change little for 3 groups.As seen, preparation of the present invention produces tangible preventive and therapeutic effect to myocardial ischemia, and can dwindle myocardial infarct size, and is better than 3 groups in preparation 1, preparation 2 and preparation; Electron microscope showed, to coronary ligation to the damage of myocardial cell, the myocardial damage degree of preparation group of the present invention also obviously is lighter than 3 groups in preparation 1, preparation 2 and preparation.
The specific embodiment:
Embodiments of the invention 1: 5 parts of Folium Ginkgo extract (in total flavonoids), 2.5 parts of dipyridamoles
Take by weighing dipyridamole, add in 60 times of amount waters for injection, regulating PH with dilute hydrochloric acid is 5, and dipyridamole is dissolved fully;
Take by weighing Folium Ginkgo extract, add in 60 times of amount waters for injection; With the solution and the dipyridamole solution mixing of Folium Ginkgo extract, add the injection water to 3000ml, regulating PH is 4, mixing filters through the filter membrane of 0.25 μ m, is filled into cillin bottle by every 2ml, lyophilizing, rolls behind the lid promptly; Freeze-drying process is: send into freeze dryer after cillin bottle half tamponade that fill is good, slowly be refrigerated to-35 ℃, be evacuated to 10-30Pa, control heat temperature raising speed is no more than 3 ℃/h and distils, distil after 20 hours, setting shelf temperature and be 30 ℃, to carry out second time dry, when products temperature and shelf temperature near the time, steady temperature drying total head plug after 4 hours.
Embodiments of the invention 2: 1 part of Folium Ginkgo extract, 5 parts of dipyridamoles
Take by weighing dipyridamole, add in 20 times of amount waters for injection, regulating PH with dilute hydrochloric acid is 3, and dipyridamole is dissolved fully; Take by weighing Folium Ginkgo extract, add in 20 times of amount waters for injection; With the solution and the dipyridamole solution mixing of Folium Ginkgo extract, add the injection water to 1000ml, regulating PH is 2.5, mixing filters through the filter membrane of 0.45 μ m, is filled into cillin bottle by every 1ml, lyophilizing, rolls behind the lid promptly; Freeze-drying process is: send into freeze dryer after cillin bottle half tamponade that fill is good, slowly be refrigerated to-20 ℃, be evacuated to 5-15Pa, control heat temperature raising speed is no more than 2 ℃/h and distils, distil after 10 hours, setting shelf temperature and be 20 ℃, to carry out second time dry, when products temperature and shelf temperature near the time, steady temperature drying total head plug after 2 hours.
Embodiments of the invention 3: 10 parts of Folium Ginkgo extract, 0.5 part of dipyridamole
Take by weighing dipyridamole, add in 100 times of amount waters for injection, regulating PH with dilute hydrochloric acid is 6, and dipyridamole is dissolved fully; Take by weighing Folium Ginkgo extract, add in 100 times of amount waters for injection; With the solution and the dipyridamole solution mixing of Folium Ginkgo extract, add the injection water to 4000ml, regulating PH is 5, mixing filters through the filter membrane of 0.1 μ m, is filled into cillin bottle by every 5ml, lyophilizing, rolls behind the lid promptly; Freeze-drying process is: send into freeze dryer after cillin bottle half tamponade that fill is good, slowly be refrigerated to-50 ℃, be evacuated to 20-35Pa, control heat temperature raising speed is no more than 1.5 ℃/h and distils, distil after 30 hours, setting shelf temperature and be 40 ℃, to carry out second time dry, when products temperature and shelf temperature near the time, steady temperature drying total head plug after 5 hours.
Claims (4)
1. ginkgo Damo freeze-drying preparation, it is characterized in that: calculate according to composition by weight: it is made in total flavonoids 1-10 part and two kinds of medicines of dipyridamole 0.5-5 part jointly by Folium Ginkgo extract.
2. the preparation method of ginkgo Damo freeze-drying preparation as claimed in claim 1 is characterized in that: dipyridamole is mixed with Folium Ginkgo extract and be dissolved in the water for injection, regulate PH to 2.5-5, add the injection water to 1000-4000ml, filter, be filled into cillin bottle, lyophilizing, roll behind the lid promptly.
3. according to the preparation method of the described ginkgo Damo freeze-drying preparation of claim 2, it is characterized in that: take by weighing dipyridamole, add 20-100 and doubly measure in the water for injection, regulate PH3～6, dipyridamole is dissolved fully with dilute hydrochloric acid; Take by weighing Folium Ginkgo extract, add 20-100 and doubly measure in the water for injection; With the solution and the dipyridamole solution mixing of Folium Ginkgo extract, add the injection water to 1000-4000ml, regulate PH2.5～5, mixing filters through the filter membrane smaller or equal to 0.45 μ m, is filled into cillin bottle by every 1-5ml, lyophilizing, rolls behind the lid promptly.
4. according to the preparation method of claim 2 or 3 described ginkgo Damo freeze-drying preparations, it is characterized in that: freeze-drying process is: send into freeze dryer after cillin bottle half tamponade that fill is good, slowly be refrigerated to below-20 ℃, be evacuated to 5-35Pa, control heat temperature raising speed is no more than 3 ℃/h and distils, and distillation is after 10-30 hour, and the setting shelf temperature is 20-40 ℃ and carries out the drying second time, when products temperature and shelf temperature near the time, steady temperature is the total head plug after dry 2-5 hour.
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|---|---|---|---|---|
| CN1454596A (en) * | 2003-05-30 | 2003-11-12 | 张哲峰 | Compound medicine of ginkgo leaf extract and dipyridamole and preparing method thereof |
| CN1481798A (en) * | 2003-07-31 | 2004-03-17 | 王景成 | Large capacity gingko damole injection and its preparation method |
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| Publication number | Publication date |
|---|---|
| CN1785217A (en) | 2006-06-14 |
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