CN1430968A - Injection liquid of extractive gingko leaves and its preparing method - Google Patents
Injection liquid of extractive gingko leaves and its preparing method Download PDFInfo
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Abstract
A ginkgo leaf extract injection is prepared from ginkgo extract, pH value regulator, antioxidizing agent and pharmacologically receptable solvent through removing tannin by gelatin, adding pH value regulator and antioxidizing agent, and dissolving in the mixture of alcohol and water. Its advantages are high content of ginkgolide and high stability.
Description
Technical field
The present invention relates to a kind of Chinese medicine injection and preparation method thereof, especially relate to gingko leaf extract injection and preparation method thereof.
Background technology
Semen Ginkgo is the distinctive ancient plant in the Far East, and its leaf is done medicinal in the history in existing several thousand of China.Pharmacological experiments over nearly 20 years shows, the expansible coronary artery of Folium Ginkgo extract, cerebral blood flow increasing amount, improves brain nutrition, also has tangible anti-platelet activating factor and antibacterial action.Ginkgo leaf extract preparation is mainly used in the treatment cardiovascular and cerebrovascular disease clinically and comprises coronary heart disease, angina pectoris, myocardial infarction, cerebral embolism, cerebral vasospasm etc.; The intermittent claudication that acra arteriospasm or thromboangiitis obliterans cause; The full syndrome of brain function comprise poor memory, absent-minded, energy decline, muscle power tired, interpersonal indifferent, consciousness is muddled, be in a very depressed state, anxiety, giddy, headache, tinnitus, asthenia etc.; Mental sickness such as schizophrenia, dysthymia.
Present studies show that: effective ingredient is total flavonoid of ginkgo, bilobalide and bilobalide in the Folium Ginkgo extract.The solid preparation of Folium Ginkgo extract comprises Folium Ginkgo, Folium Ginkgo capsule, Folium Ginkgo granule etc.They are all stipulated the content of total flavonoid of ginkgo, bilobalide and bilobalide in the preparation.Because bilobalide is very unstable, bring certain degree of difficulty for the preparation of injection.Germany develops in the big pharmaceutical factory of Shu Pei the YINXINGYE ZHUSHEYE of the commodity Ginaton (Ginaton) by name that gone on the market, and every injection also has Folium Ginkgo extract 17.5mg, demarcates to contain Semen Ginkgo total flavones 4.2mg, bilobalide and bilobalide is not made stipulations.Also disclose a kind of YINXINGYE ZHUSHEYE and preparation method thereof among the Chinese patent CN1162474SA, but the quality of the pharmaceutical preparations has not been made clear and definite regulation.
Summary of the invention
One of technical problem of solution required for the present invention provides a kind of gingko leaf extract injection, two of the technical problem of solution required for the present invention provides a kind of preparing ginkgo biloba leaf extract injection, lower to overcome in the prior art content of bilobalide, the shortcoming and defect of less stable.
Design of the present invention is as follows: (1) contains mentioned component because bilobalide is water insoluble if will make in the gingko leaf extract injection that makes, and need select suitable solvent for use; (2) because the bilobalide instability need select for use proper auxiliary agent to increase its stability; (3), need to use suitable antioxidant because total flavonoid of ginkgo is easily oxidized; (4) on inspection as can be known, contain tannin in the Folium Ginkgo extract, the clarity of its appreciable impact injection also can produce zest, therefore must eliminate tannin when the preparation injection.
Technical scheme of the present invention is as follows:
A kind of gingko leaf extract injection is made up of the Folium Ginkgo extract that contains effective ingredient, pH value regulator, antioxidant and medically acceptable solvent.
Injection each component content of the present invention is as follows:
Total flavonoid of ginkgo: 24%～60%, account for the weight ratio of Folium Ginkgo extract,
Bilobalide: 6%～15%, account for the weight ratio of Folium Ginkgo extract,
Ginkgolic acid: 0～2ppm,
Injection solvent volume ratio of alcohol to water: (0.1～0.4): 1.
Owing to contain liposoluble constituents such as bilobalide in the Folium Ginkgo extract, separately with water for injection as solvent, bilobalides etc. can not dissolve, so select for use a certain proportion of alcohol-water mixture as molten coal.The ratio of alcohol is suitable, and higher meeting brings side reactions such as haemolysis, zest, on the low sidely can not dissolve liposoluble constituent such as bilobalide.The selected pure water ratio of the present invention is 0.1～0.4: 1 (volume ratio).Employed alcohol is ethanol, 1 for example, and 2-propylene glycol etc. also can be the mixture of alcohol, as ethanol and 1, and the mixture of 2-propylene glycol etc.
The easy oxidation of total flavonoid of ginkgo and bilobalide is so use antioxidant in the prescription of injection.The selected antioxidant of the present invention is sodium sulfite, sodium pyrosulfite, cysteine etc. for example.
Injection must satisfy certain pH value, in the prescription of Chinese medicine pH value is defined as 4.0～9.0.Owing to also have many not principal components in the Folium Ginkgo extract, constant and improve the stability of this injection for keeping pH value, the present invention has used the pH value regulator.The selected pH value regulator of the present invention is acetic acid-sodium acetate, citric acid-sodium citrate, lactic acid etc. for example.
Preparing ginkgo biloba leaf extract injection is as follows: (1) gets Folium Ginkgo extract by 120% of recipe quantity, adds 90% dissolve with ethanol; (2) slowly add gelatin solution while stirring and extremely no longer produce till the precipitation, leave standstill aseptic filtration; (3) filtrate carries out waving to no ethanol flavor after the tannin passed examination; (4) get pH value regulator, antioxidant in addition, with the water for injection dissolving, the consumption of antioxidant is 0.05%～0.2%, and liquor capacity percentage ratio adds in the above-mentioned solution, regulates pH value between 3.5～7.5; (4) add the alcohol of 0.1～0.4 (volume ratio), add to the full amount of water for injection.(5) needle-use activated carbon of adding 0.5 ‰～1.5 ‰ liquor capacity percentage ratios, charcoal is taken off in 60 ℃ of following cores circulations, filters.(6) after the filtrate passed examination, fill, inflated with nitrogen, sealing by fusing.(7) circulation steam sterilization, promptly.
Good conditions is in the preparation method of the present invention:
Employed alcohol is any of mixture of any or they in following: ethanol, 1,2-propylene glycol, glycerol, Polyethylene Glycol.
Employed antioxidant is any in following: sodium sulfite, sodium pyrosulfite, cysteine, methionine, vitamin C or thiourea.
Employed pH value regulator is any in following: acetic acid-sodium acetate, citric acid-sodium citrate, lactic acid, tartaric acid-sodium tartrate, phosphate system such as sodium hydrogen phosphate (potassium)--sodium dihydrogen phosphate (potassium), carbonate system such as sodium bicarbonate-sodium carbonate, buffer such as sodium hydrogen phosphate-citric acid.
Using gelatin in the preparation method of the present invention is in order to remove tannin.When removing tannin, have improvement gelatin method, alcoholic solution commonly used are transferred pH method and polyamide method.Because the index components total flavonoids of polyamide absorption this product is so can not use.Utilize improvement gelatin method and alcoholic solution to transfer the pH method to remove the contained tannin of this product, the result shows that alcoholic solution transfers the pH method can not remove the tannin in this product effectively and influence the stability of this product index components bilobalide, and improvement gelatin method can effectively be removed tannin and less to the absorption of total flavonoids, therefore selects for use improvement gelatin method to remove tannin.
In improvement gelatin method, the gelatin typical concentrations is 2%～5%.
Among the present invention preferably pH value be adjusted between 4.0～4.5.
When using the circulation vapor method to sterilize, preferred condition is 110～115 ℃ of pressure sterilizing 20～30min.The long stability that can influence bilobalide of temperature height or time; Low or time of temperature is short then can cause sterilization not exclusively.
Injection of the present invention has improved the stability of bilobalide in the Folium Ginkgo extract, a kind of gingko leaf extract injection that contains total flavonoid of ginkgo, bilobalide and bilobalide is provided, improved the stability of bilobalide in the Folium Ginkgo extract, and this composition of bilobalide is still stable in the put procedure of preparation.
The The pharmacological results of injection of the present invention is as follows:
Pharmacodynamics test
1, gingko leaf extract injection is to the protective effect of rat local cerebral ischemia
Utilize intraluminal middle cerebral artery occlusion in rats to block (MCAO) model and observe the influence of gingko leaf extract injection focal cerebral ischemic injury, and with positive drug Ginaton
Injection compares.60 of adult male SD rats, body weight 251.85 ± 10.34g, be divided into 6 groups at random, every group 10, be respectively model control group, vehicle treated group, positive controls, the large, medium and small dosage group of gingko leaf extract injection, through tail vein injection saline, solvent for injection, Ginaton 15mg/kg, gingko leaf extract injection 30,15,7.5mg/kg, each injection in 2 hours once after ischemia reaches ischemia at once successively.With reference to the method for Longa etc. rat function of nervous system defect situation was marked in 8 and 24 hours behind the ischemia, last scoring pneumoretroperitoneum is injected excessive chloral hydrate and is put to death animal, gets brain rapidly and measures cerebral tissue swelling degree and cerebral infarction scope.The result shows that 24 hours function of nervous system's defectives are compared have clear improvement (P＜0.05) in the gingko leaf extract injection, behind the small dose group rat ischemia with model control group, compare no significant difference (P＞0.05) with positive controls; Each dosage group rat cerebral tissue swelling degree of gingko leaf extract injection and cerebral infarction scope are compared all have clear improvement (P＜0.05) with model control group, compare no significant difference (P＞0.05) with positive controls.Result of the test prompting gingko leaf extract injection injection has the effect that improves focal cerebral ischemia injury, and its effect with dosage Ginaton
Injection is compared no significant difference.
2, gingko leaf extract injection is to the influence of dog cerebral blood flow and blood pressure
This laboratory observation the influence of gingko leaf extract injection and its solvent to dog cerebral blood flow, systolic pressure, diastolic pressure.8 of dogs, male and female dual-purpose, body weight 11.2 ± 1.8kg.1.25,2.5,5.0mg/kg gingko leaf extract injection and its solvent are established 3 dosage groups respectively, gingko leaf extract injection:; And with the solvent of the suitable capacity of above-mentioned dosage: 0.025,0.05,0.1ml/kg, as the solvent control group.Before each administration and measured cerebral blood flow, systolic pressure and the diastolic pressure of dog after the administration in 1,3,5,10,15,20,30 minutes respectively.First three dosage solvents of sequential intravenous injection during experiment, the solvent administration finishes, treat cerebral blood flow and blood pressure recover substantially normal after, give gingko leaf extract injection again.The result shows: behind intravenous injection solvent 0.025,0.05, the 0.1ml/kg, and compare before the administration, cerebral blood flow, systolic pressure, diastolic pressure are not had obvious influence.Intravenous injection gingko leaf extract injection 1.25mg/kg, cerebral blood flow there is not obvious effect, intravenous injection gingko leaf extract injection 2.5,5.0mg/kg, 1～5 minute obvious cerebral blood flow increasing amount (P＜0.05, P＜0.01), compares, significant difference (P＜0.05 is arranged with corresponding solvent group, P＜0.05), recovers substantially after 10 minutes.Behind the gingko leaf extract injection of three dosage of intravenous injection, in various degree reduction is all arranged, recover substantially after 10 minutes at 1～5 minute systolic pressure and diastolic pressure.The gingko leaf extract injection of The above results prompting 2.5mg/kg and 5.0mg/kg dosage group has the effect of obvious increase dog cerebral blood flow.
3, gingko leaf extract injection and solvent thereof are to the influence of Medulla Leporis seu Oryctolagi blood flow and blood pressure
This laboratory observation the influence of gingko leaf extract injection and its solvent to Medulla Leporis seu Oryctolagi blood flow, systolic pressure, diastolic pressure.8 of rabbits, male and female dual-purpose, body weight 2.6 ± 0.2kg.Gingko leaf extract injection and its solvent are established 3 dosage groups respectively, are 2.5,5.0,10.0mg/kg; Be 0.05,0.1 with the solvent of above-mentioned suitable capacity, 0.2ml/kg, as the solvent control group.Before each administration and measured cerebral blood flow, systolic pressure and the diastolic pressure of rabbit after the administration in 1,3,5,10,15,20,30 minutes respectively.Solvent writing time is 1,5,10 minutes.The solvent of three dosage of sequential intravenous injection earlier during experiment after the solvent administration finishes, after cerebral blood flow and blood pressure recover normally substantially, is given gingko leaf extract injection again.Observed of the influence of positive control drug-Ginaton injection with same experimental technique to Medulla Leporis seu Oryctolagi blood flow, systolic pressure, diastolic pressure.8 of rabbits, male and female dual-purpose, body weight 2.5 ± 0.17kg.2.5,5.0,10.0mg/kg establish three dosage groups altogether:.The first Ginaton injection of three dosage groups of sequential intravenous injection during experiment is before each administration and measured cerebral blood flow, systolic pressure and the diastolic pressure of rabbit after the administration in 1,3,5,10,15,20,30 minutes respectively.Experimental result shows: behind intravenous injection solvent 0.05,0.1, the 0.2ml/kg, cerebral blood flow, systolic pressure, diastolic pressure all do not have obvious change.Behind intravenous injection gingko leaf extract injection 2.5,5.0, the 10.0mg/kg, cerebral blood flow increases at once, 2.5mg/kg group effect maximum wherein, and the increase of cerebral blood flow in the time of 15 minutes is compared significant difference with corresponding solvent.The gingko leaf extract injection of three dosage groups does not all have obvious influence to systolic pressure and diastolic pressure.Intravenous injection Ginaton injection 2.5,5.0,10.0mg/kg have the effect of cerebral blood flow increasing amount, wherein compare difference work property (p＜0.05) before 10.0mg/kg group and the administration.The Ginaton of three dosage groups does not all have obvious influence to systolic pressure and diastolic pressure.The effect of gingko leaf extract injection 2.5mg/kg and Ginaton 10.0mg/kg is compared, and the T check shows no significant difference between two groups, points out the action intensity of two groups of medicines close.
Above results suggest, 2.5mg/kg dosage group gingko leaf extract injection has the effect of obvious increase Medulla Leporis seu Oryctolagi blood flow, and the effect of its action intensity and Ginaton injection 10.0mg/kg dosage group is close.
4, gingko leaf extract injection is to the effect of isolated rat papillary muscles of left ventricle
Observe the effect of gingko leaf extract injection to the isolated rat papillary muscles of left ventricle.Rat is taken out heart rapidly after tapping the head and putting to death, and opens left ventricle, exposes left chamber papillary muscles.With cutting behind No. 0000 silk thread ligation anterior papillary muscle chordae tendineae end, be fixed in the thermostatic bath resting tension 1g.Begin electricity irritation after the balance 30 minutes (every changing one time of nutrition liquid in 15 minutes), treat shrinkage curve before the recording medicine of the stable back of its shrinkage amplitude, administration then, the shrinkage curve behind the recording medicine in 10 minutes calculates the variation percentage rate that the ventricle papillary muscles shrinks.The result shows: the interior cumulative concentration of the bath of 25ml gives 5% gingko leaf extract injection, 0.125～1ml, and (final concentration of Folium Ginkgo extract is 0.5～2mg/ml) in the bath, but concentration dependent increases the contractility of papillary muscles; And give the solvent of same capability, then concentration dependent weakens the contractility of papillary muscles.Gingko leaf extract injection (containing solvent) increases the EC that papillary muscles shrinks
50Be 10.23mg/ml, the 95% credible 1.89～55.32mg/ml that is limited to; Gingko leaf extract injection increases the EC that papillary muscles shrinks after getting rid of the solvent effect
50Be 0.94mg/ml, the 95% credible 0.49～1.83mg/ml that is limited to, difference of them is (p＜0.05) significantly.
General pharmacology research
Experimental observation gingko leaf extract injection and its solvent to the influence of spontaneous activity in mice, coordination exercise and to the influence of dog heart rate, EGC parameter, blood pressure, breathing.1, the gingko leaf extract injection intravenously administrable is to the influence of spontaneous activity in mice: 60 of Kunming mouses, and male and female half and half, body weight 19.37 ± 0.89g is divided into 5 groups, 12 every group.If 3 medication groups and 2 matched groups (normal saline and solvent).Medication group dosage is respectively 10.5,21 and 42mg.kg
-1, matched group waits capacity normal saline or solvent.Equal one week of successive administration of experiment mice, and before administration and the 1st, 5,10 minutes of administration measure the spontaneous activity ripple of respectively organizing mice, METHOD FOR CONTINUOUS DETERMINATION 15 seconds.The result shows with the normal saline group and compares, but the short time is obviously suppressed the spontaneous activity of mice behind the intravenous injection solvent, effect is tending towards disappearing after 10 minutes, 1 and 5 minute spontaneous activity and normal saline group more also have obvious minimizing after the administration of gingko leaf extract injection various dose group mice, but it is similar to the solvent group, no significant difference points out this inhibitory action may be relevant with the solvent in the preparation.2, the gingko leaf extract injection intravenously administrable is to the influence of mice coordination exercise: use the pole-climbing method and observe the influence of intravenous injection gingko leaf extract injection to the mice coordination exercise.60 of Kunming mouses, male and female half and half, body weight 19.96 ± 0.98g is divided into 5 groups at random, 12 every group.The normal saline or the solvent of capacity such as matched group intravenous injection, the medication group is intravenous injection gingko leaf extract injection 10.5,21 and 42mgkg respectively
-1, after administration, measured mice coordination exercise ability in 1,10,20 and 30 minute, the coordination exercise ability represents that with the 0-3 level data are represented with X ± SD, adopt the rank test method to carry out analyzing and processing (each group and matched group are relatively).The result as seen, after the administration 1 minute, identical before normal saline group mice and the medication, be 0 grade; The solvent matched group, little, in, heavy dose of gingko leaf extract injection group part mice is the 1.5-2 level, with the normal saline group relatively, the coordination exercise ability obviously is subjected to press down (p＜0.01), does not have significant difference (p＞0.05) between medication group and the solvent group; Mice coordination exercise ability is recovered normally and the normal saline group does not relatively have marked difference (P＞0.05) and 10 minutes to 30 minutes each time point are respectively organized.3, the gingko leaf extract injection intravenously administrable is to the influence of dog heart rate, EGC parameter, blood pressure, breathing: 8 of dogs, male and female dual-purpose, body weight 11.2 ± 1.8kg.Gingko leaf extract injection is established 3 dosage groups, is respectively 1.25,2.5,5.0mg/kg; Be 0.025,0.05 with the solvent of the suitable capacity of above-mentioned dosage, 0.01ml/kg, as solvent control.Intravenously administrable was measured dog systolic pressure, diastolic pressure, mean arterial pressure, heart rate, EGC parameter and respiratory variations before each administration and after the administration in 1,3,5,10,15,20,30 minutes respectively.First three dosage solvents of sequential intravenous injection during experiment, after the solvent administration finishes, treat each experiment parameter recover substantially normal after, give gingko leaf extract injection again.The result shows: compares before the solvent of three dosage groups, its each time period and administration, and to the dog systolic pressure, diastolic pressure, mean arterial pressure, breathing and heart rate, EGC parameter all do not have obvious change.The gingko leaf extract injection of three dosage groups is compared to before the systolic pressure of dog, diastolic pressure, mean arterial pressure, heart rate and the medication, 1～5 minute systolic pressure after administration, diastolic pressure, mean arterial pressure reduces, and with decreased heart rate, with comparison before the administration, significant difference compares with solvent, and also there were significant differences, wherein the effect of 2.5mg/kg is stronger, and this blood pressure and changes in heart rate were recovered in 30 minutes substantially.Gingko leaf extract injection and solvent do not have obvious influence to the dog respiratory frequency.Experimental result shows that gingko leaf extract injection has the effect of of short duration systolic pressure, diastolic pressure reduction and decreased heart rate after administration.
Acute toxicity test
Mice single intravenous injection gingko leaf extract injection 17.5ml/kg (Folium Ginkgo extract 875mg/kg, this dosage are 100 times of mice effective dose) observes its acute toxic reaction to mice.The result is as follows: in the Folium Ginkgo extract group mice, except 1 male Mus after medication the death in 10 minutes, all the other mices lethargy in 10 minutes after medication flatly crouches motionlessly, recovers gradually after 20 minutes, observes and does not see death in 7 days.Male Mus: LD
50＞875mg/kg; Female Mus: LD
50＞875mg/kg.There is not significant difference between the male and female mice.
Safety testing
Comprise the test of intravenous injection blood vessel irritation, local irritation, hemolytic test and hypersensitive test.The result shows that gingko leaf extract injection does not have blood vessel irritation and local irritation, can not cause haemolysis and allergy.
Long term toxicity test
1, dog long term toxicity test
Observe continuous 12 all intravenous injection gingko leaf extract injections, to the toxic reaction of dog generation.17 of Beagle dogs are divided into 4 groups at random, and promptly heavy dose group, solvent group, small dose group are respectively 5 (female 2, male 3), 2 of matched groups (female 2), wherein heavy dose of group and small dose group intravenous injection gingko leaf extract injection are respectively 95mgkg with Folium Ginkgo extract calculating
-1(1.9mlkg
-1), 9.5mgkg
-1(0.19mlkg
-1), solvent group intravenous injection solvent 1.9mlkg
-1, matched group intravenous injection normal saline 1.9mlkg
-1, every day 1 time, administration is 6 days weekly, altogether 12 weeks of administration.Observe body weight and other the general situations of dog during the medication, carry out hematology, blood biochemical, electrocardiogram, routine urianlysis before the medication and after the medication per 4 weeks, experiment finishes laggard capable hematology, blood biochemical, electrocardiogram, routine urianlysis.Every group is stayed 1 dog then, and all the other sacrifice of animal are measured organ coefficient and carried out pathological examination.Do not continue to observe the back execution of 3 weeks after putting to death the dog drug withdrawal, repeat above-mentioned detection.Result of the test shows, in the process of the test between each treated animal food ration and body weight change no significant difference.Each treated animal blood and blood biochemical are learned index and be there is no obvious change.Pathologic finding shows, heavy dose of group, small dose group, each organ of solvent group dog there is no the toxic reaction relevant with medicine.
2, rat long term toxicity test
Observe continuous 12 all lumbar injection gingko leaf extract injections, to the toxic reaction of rat generation.60 of SD rats, male and female half and half are divided into 3 groups at random, and 20 every group, be respectively matched group, small dose group and heavy dose of group, wherein heavy dose of group and small dose group lumbar injection gingko leaf extract injection, dosage is respectively 750,75mgkg
-1(calculating) with Folium Ginkgo extract, matched group lumbar injection solvent (15mlkg
-1), every day 1 time, administration is 6 days weekly, stops 1 day, altogether 12 weeks of administration.Observe rat body weight and other general situations during the medication, experiment finishes back execution 2/3 animal and carries out inspections such as hematology, blood biochemical, pathology, organ coefficient; Continue after all the other 1/3 animal drug withdrawals to observe for 4.5 weeks, put to death then, repeat above-mentioned detection.Result of the test shows, in the process of the test between each treated animal food ration and body weight change no significant difference, during the medication, heavy dose of treated animal has 2 rats deaths in 11 weeks of medication, small dose group is not seen animal dead.Each treated animal blood and blood biochemical are learned index and be there is no obvious change.Pathologic finding shows that the pathological change of heavy dose of group is relevant with the local inflammation reaction that lumbar injection causes, can avoid as changing route of administration.
Injection of the present invention provides a kind of gingko leaf extract injection that contains total flavonoid of ginkgo, bilobalide and bilobalide.Prove that through pharmacodynamics test and pharmacological research this injection has the good cardiovascular function effect that improves, and toxicity test shows and does not see toxic reaction.The inventive method raw material sources are extensive, operating process is simple, realizes easily on the technology that main is that the present invention has improved the content and the stability of bilobalide in the product, and bilobalide still shows stable in preparation is deposited, and product drug effect of the present invention is significantly improved.
The specific embodiment
Embodiment 1 gingko leaf extract injection prescription:
Per 1000 consumptions
Folium Ginkgo extract 17.5g
Acetic acid 9.8ml
Sodium acetate 18g
Sodium sulfite 5g
Ethanol 250ml
1,2-propylene glycol 250ml
Water for injection 5000ml
Preparing ginkgo biloba leaf extract injection is as follows:
Get Folium Ginkgo extract 17.5g (feeding intake), add injection water 50ml, ethanol 450ml dissolving by 120% of recipe quantity; Slowly add 4% gelatin while stirring and extremely no longer produce till the precipitation, left standstill 30 minutes, with aseptic buchner funnel shop dual-layer sterilization filter paper sucking filtration; Filtrate carries out waving to no ethanol flavor in 60 ℃ of water-baths after the tannin passed examination; Other gets acetic acid 9.8ml, acetic acid and receives 18g and add injection water 1000ml dissolving, adds to wherein, adds water to 3000ml; Add sodium sulfite 5g, stirring and dissolving; Add ethanol 250ml, 1,2 propylene glycol 250ml, 5000ml adds to the full amount of water for injection.Add needle-use activated carbon 2.5g (0.5 ‰), 60 ℃ of following cores circulated 20 minutes, took off charcoal, 0.45 μ m membrane filtration.After the filtrate passed examination, press every loading amount 5ml fill in the brown ampoule of 5ml, inflated with nitrogen, sealing by fusing.115 ℃ of pressure sterilizing 30min, promptly.Embodiment 2 gingko leaf extract injections prescription:
Per 1000 consumptions
Folium Ginkgo extract 17.5g
Potassium dihydrogen phosphate 4.2g
Dipotassium hydrogen phosphate 0.44g
Sodium sulfite 10g
Ethanol 250ml
1,2-propylene glycol 1000ml
Water for injection 5000ml
Preparing ginkgo biloba leaf extract injection is as follows: get Folium Ginkgo extract 17.5g (feeding intake by 120% of recipe quantity), add injection water 50ml, ethanol 450ml dissolving; Slowly add 4% gelatin while stirring and extremely no longer produce till the precipitation, left standstill 30 minutes, with aseptic buchner funnel shop dual-layer sterilization filter paper sucking filtration; Filtrate carries out waving to no ethanol flavor in 60 ℃ of water-baths after the tannin passed examination; Other gets potassium dihydrogen phosphate 4.2g, dipotassium hydrogen phosphate 0.44g and adds injection water 1000ml dissolving, adds to wherein, adds water to 3000ml; Add sodium sulfite 10g, stirring and dissolving; Add ethanol 250ml, 1,2 propylene glycol 1000ml, 5000ml adds to the full amount of water for injection.Add needle-use activated carbon 7.5g (1.5 ‰), 60 ℃ of following cores circulated 20 minutes, took off charcoal, 0.45 μ m membrane filtration.After the filtrate passed examination, press every loading amount 5ml fill in the brown ampoule of 5ml, inflated with nitrogen, sealing by fusing.115 ℃ of pressure sterilizing 30min, promptly.
Claims (8)
1, a kind of gingko leaf extract injection contains the effective ingredient of Folium Ginkgo extract and medically acceptable solvent, it is characterized in that each component content is:
Total flavonoid of ginkgo: 24%～60%, account for the weight ratio of Folium Ginkgo extract
Bilobalide: 6%～15%, account for the weight ratio of Folium Ginkgo extract
Ginkgolic acid: 0～2ppm
Injection solvent volume ratio of alcohol to water: 0.1～0.4: 1.
2, gingko leaf extract injection according to claim 1 is characterized in that preparing as follows:
(1) gets Folium Ginkgo extract, add dissolve with ethanol;
(2) slowly add gelatin solution while stirring and extremely no longer produce till the precipitation, leave standstill aseptic filtration;
(3) filtrate carries out waving to no ethanol flavor after the tannin passed examination;
(4) get pH value regulator, antioxidant in addition, with the water for injection dissolving, add in the above-mentioned solution, pH value is adjusted between 3.5～7.5, and the consumption of antioxidant is 0.05%～0.2% liquor capacity percentage ratio;
(5) add the alcohol of 0.1～0.4 volume ratio, add to the full amount of water for injection;
(6) needle-use activated carbon of adding 0.5 ‰～1.5 ‰ liquor capacity percentage ratios, charcoal is taken off in the core circulation, filters;
(7) after the filtrate passed examination, fill, inflated with nitrogen, sealing by fusing;
(8) circulation steam sterilization, promptly.
3, gingko leaf extract injection according to claim 2 is characterized in that employed alcohol is any of mixture of any or they in following: ethanol, 1,2-propylene glycol, glycerol, Polyethylene Glycol.
4, gingko leaf extract injection according to claim 2 is characterized in that employed antioxidant is any in following: sodium sulfite, sodium pyrosulfite, cysteine, methionine, vitamin C, thiourea.
5, gingko leaf extract injection according to claim 2 is characterized in that employed pH value regulator is any in following: acetic acid-sodium acetate, citric acid-sodium citrate, lactic acid, tartaric acid-sodium tartrate, phosphate system, carbonate system, sodium hydrogen phosphate-citrate buffer.
6, gingko leaf extract injection according to claim 2, the concentration that it is characterized in that employed gelatin solution is 2%～5%.
7, gingko leaf extract injection according to claim 2 is characterized in that pH value is adjusted between 4.0～4.5.
8, gingko leaf extract injection according to claim 2 is characterized in that 110～115 ℃ of pressure sterilizing 20～30min.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101596221B (en) * | 2008-06-04 | 2012-06-20 | 上海信谊百路达药业有限公司 | Process for preparing water-soluble ginkgo biloba extract used for injection |
| CN102626383A (en) * | 2012-04-23 | 2012-08-08 | 成都百裕科技制药有限公司 | Bilobalide injection and preparation method thereof |
| CN103751061A (en) * | 2014-01-23 | 2014-04-30 | 广州丹奇日用化工厂有限公司 | Tomato leaf extract and application thereof in cosmetics |
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2003
- 2003-01-30 CN CN 03115286 patent/CN1430968A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101596221B (en) * | 2008-06-04 | 2012-06-20 | 上海信谊百路达药业有限公司 | Process for preparing water-soluble ginkgo biloba extract used for injection |
| CN102626383A (en) * | 2012-04-23 | 2012-08-08 | 成都百裕科技制药有限公司 | Bilobalide injection and preparation method thereof |
| CN103751061A (en) * | 2014-01-23 | 2014-04-30 | 广州丹奇日用化工厂有限公司 | Tomato leaf extract and application thereof in cosmetics |
| CN103751061B (en) * | 2014-01-23 | 2016-01-20 | 广州千百度化妆品有限公司 | Tomato leaf extract and the application in cosmetics |
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