CN1895298A - Medicinal preparation for treating and preventing coronary heart disease and thromboembolia disease and its preparation - Google Patents
Medicinal preparation for treating and preventing coronary heart disease and thromboembolia disease and its preparation Download PDFInfo
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- CN1895298A CN1895298A CN 200610051010 CN200610051010A CN1895298A CN 1895298 A CN1895298 A CN 1895298A CN 200610051010 CN200610051010 CN 200610051010 CN 200610051010 A CN200610051010 A CN 200610051010A CN 1895298 A CN1895298 A CN 1895298A
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Abstract
A medicine for preventing and treating coronary heart disease and thrombotic diseases is prepared from gingko flavone, dipyridamole and excipient. Its preparing process is also disclosed.
Description
Technical field: the present invention relates to pharmaceutical preparation of a kind of prevention and treatment coronary heart disease, thrombotic disease and preparation method thereof, belong to the field of medicine technology.
Technical background: cardiovascular and cerebrovascular disease is first killer of harm humans life and health, and coronary heart disease and thrombus disease are one of chief-criminals wherein, and in recent years, sickness rate both domestic and external rises gradually, in western countries, only the annual morbidity of thromboembolism is about 1 ‰ and 0.5 ‰ respectively.In China, coronary heart disease and thrombosis equally also are commonly encountered diseases, frequently-occurring disease, and its sickness rate is rapid ascendant trend, make it become first of global general mortality rate.The clinical symptoms that coronary heart disease may cause: angina pectoris, myocardial infarction (abbreviation heart infarction), arrhythmia, heart failure and sudden death, the complexion changed that any one all allows the people hear, and thrombosis is the final key link that causes the heart, brain and peripheral blood vessel incident, be the lethal immediate cause that disables, do not have the cardiovascular and cerebrovascular vessel incident without thrombosis.The whole mankind is faced with the huge challenge of these two kinds of diseases now, and the guide that presses for applied science instructs the diagnosis and the treatment of cardiovascular and cerebrovascular disease.Therefore, the control of this type of disease needs the omnibearing stereo measure, importantly will set up with " preventing " idea for the multidisciplinary intersection of advocating peace.Current society, because development of natural science, fundamental research and The application of new technique, cardiovascular and cerebrovascular vessel research has had significant progress, although cardiovascular and cerebrovascular disease has become human lethal the first reason, the progress of cardiovascular and cerebrovascular vessel can make the patient effectively be prevented and treat.Wherein company produces the Ginkgo Leaf Extract and Dipyridamole Injection of listing under the applicant; it is by Folium Ginkgo extract (ginkgetin glycosides; the terpenoid terpene lactones; bilobalide) forms with dipyridamole; show through a large amount of clinical test results; said preparation has the hemodynamics of improvement; microcirculation improvement; reduce blood viscosity; increase erythrocyte deformability; antagonism platelet activity factor and the effect of removing free radical; can the expansion artery blood vessel; blood circulation promoting; suppress thrombosis and improve the cerebral tissue blood supply; the protection brain cell; for urgency; the chronic ischemic cerebrovascular disease all has curative effect preferably; be to be used for the treatment of ischemic cardio cerebrovascular diseases at present both at home and abroad; coronary heart disease; angina pectoris; cerebral embolism, one of better medicine of diseases such as cerebral vasospasm.Although the said preparation curative effect is preferable, but in clinical application, still can produce various untoward reaction, for example: allergic rash, anaphylactic shock, aberration, the inventor has carried out a large amount of research for this reason, the unit content of finding dipyridamole in the preparation is 0.36～0.44mg/ml, this content range has restriction, causes untoward reaction and instability easily.For this reason, we carry out a series of improvement to former Ginkgo Leaf Extract and Dipyridamole Injection prescription.
Summary of the invention: the object of the present invention is to provide pharmaceutical preparation of a kind of prevention and treatment coronary heart disease, thrombotic disease and preparation method thereof, this preparation is combined by Ginkgo total flavones, dipyridamole and excipient science, this pharmaceutical preparation comprises ejection preparation and oral formulations, ejection preparation can be injection, freeze-dried powder, high-capacity injection, and oral formulations can be dosage forms such as oral liquid, capsule, tablet, pill; Preparation method disclosed by the invention can be scientific and reasonable guidance production, reduced the untoward reaction of preparation in clinical, improve stability of formulation, thereby guarantee stability and the effectiveness and the safety of product.
The dipyridamole unit content in the minimizing prescription the present invention is directed to prior art, finds: if will effectively reduce the untoward reaction of this product through a series of experiments.This is because Folium Ginkgo extract contains the insoluble compositions of water such as Ginkgo total flavones, terpene lactone, and ginkgo bilobate extract is in solution state preservation process, and the biological ketone of its Folium Ginkgo extract effective ingredient easy polymerization becoming macromole causes allergic reaction easily.And in dipyridamole content maintains a certain scope the time, just can effectively stop the biological ketone of Folium Ginkgo extract effective ingredient easy polymerization becoming macromole, thereby reduce the anaphylaxis probability.Simultaneously, the inventor finds again: when silver contains the total flavones unit content when constant, only reduce the dipyridamole unit content, help product stability and strengthen, aberration can not occur.Find in addition: if after we make the folding ejection preparation with said preparation, not only can more effectively overcome the above problems, and therapeutic effect the best, because the cardiovascular and cerebrovascular disease morbidity is anxious, the course of disease is short, needs instant rapidly giving approximately.Simultaneously, the present invention feeds intake with crude drug, and the preparation repeatability is better, and each material does not almost have the content difference;
The present invention constitutes like this:
The pharmaceutical preparation of a kind of prevention and treatment coronary heart disease, thrombotic disease, it is characterized in that: the preparation that Folium Ginkgo extract and dipyridamole are mixed and made into is by cubage: every preparation unit contains total flavonoids and should be 0.90～1.10mg, dipyridamole should be 0～0.36mg, and wherein ejection preparation is in every ml unit content.Also contain additives in the preparation.
With this pharmaceutically active substance is that raw material adds the medicine acceptable auxiliary, can be made into any pharmaceutical dosage forms according to the galenic pharmacy routine techniques.
Chinese medicine preparation of the present invention can be any pharmaceutically useful dosage form, and these dosage forms comprise: injection preparation, oral liquid, oral liquid solid preparation.Wherein injection preparation comprises: injection liquor, freeze-dried powder, powder injection formulation, high capacity ejection preparation and oral formulations: comprise oral liquid, capsule, tablet or pill.
Injection preparation acceptable carrier of the present invention can be any carrier (or claiming adjuvant, excipient) that is fit to make pharmaceutical preparation.Described carrier is selected from: cosolvent, analgesic is regulated the osmotic pressure agent, PH regulator, filler, solvent for injection, antiseptic, antioxidant, protective agent etc.
Described cosolvent comprises the 1-4% Tween 80, propylene glycol or sodium bicarbonate etc., described analgesic comprises 1% benzyl alcohol, 5% procaine hydrochloride or 5% glucose etc., the agent of described adjusting osmotic pressure comprises 0.9% sodium chloride, glucose, phosphate or citrate salt etc., described PH regulator comprises meglumine, hydrochloric acid, citric acid, sodium hydroxide, potassium hydroxide, sodium bicarbonate, sodium hydrogen phosphate or sodium dihydrogen phosphate etc., described solvent for injection comprises water, ethanol, Oleum Sesami, Oleum Camelliae or Semen arachidis hypogaeae wet goods, described filler comprises mannitol, lactose, mannitol, xylitol, maltose, glucose, glucosan, fructose, dextran, glycine etc., other compositions that can add comprise glycerol, ethanol, sorbitol, sorbic acid or potassium salt, soil temperature 60, Arlacel-80, gelatin, polyvinylpyrrolidone, hexadecanol, gallate ester, agar, triethanolamine, basic amino acid, carbamide, the allantoin surfactant, Polyethylene Glycol, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, vitamin A, vitamin C, vitamin E, vitamin D, azone, the EDTA disodium, EDTA calcium sodium, the alkali-metal carbonate of monovalence, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid, aminoacid, potassium chloride, sodium lactate, starch, sucrose, silicon derivative, cellulose and derivant thereof, phospholipid material etc.
For oral drugs, preparation of the present invention can contain additives commonly used, such as sweeting agent, binding agent, filler, diluent, tablet agent, lubricant, disintegrating agent, coloring agent, correctives and wetting agent, can carry out coating to tablet in case of necessity.
Described oral solid formulation acceptable carrier is preferably from mannitol, sorbitol or potassium salt, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, vitamin C or A or D or E, the EDTA disodium, EDTA calcium sodium, the alkali-metal carbonate of monovalence, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid, aminoacid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch and derivant thereof, sucrose, lactose, mannitol, silicon derivative, cellulose and derivant thereof, alginate, gelatin, polyvinylpyrrolidone, glycerol, soil temperature 80, agar, calcium carbonate, calcium bicarbonate, surfactant, Polyethylene Glycol, cyclodextrin, beta-schardinger dextrin-, the phospholipid material, Kaolin, Pulvis Talci, micropowder silica gel, magnesium carbonate, calcium stearate, magnesium stearate etc.
Described oral liquid acceptable carrier is preferably from the additive of various routines: such as correctives, for example pulp, sucrose, aspartame, fruit Fructus Vitis viniferae slurry, fructose, maltose alcohol, stabilizing agent, for example carboxymethyl cellulose sodium, sorbitol, syrup, methylcellulose, gelatin, hydroxyethyl-cellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenation edible fat, emulsifying agent, for example lecithin, anhydro sorbitol monooleate or arabic gum; Non-aqueous carrier (they can comprise edible oil), for example almond oil, fractionated coconut oil, such as oily ester, propylene glycol or the ethanol of the ester of glycerol; Antiseptic, for example sodium benzoate or propylene glycol or para hydroxybenzene methyl ester or propyl p-hydroxybenzoate or sorbic acid, and if desired, can contain conventional flavouring agent or coloring agent.
The preparation method of pharmaceutical preparation of the present invention: calculate according to unit content: essence is got Ginkgo total flavones extract and dipyridamole mix homogeneously respectively, adds different adjuvants again, makes different products with different conventional methods.
For injection preparation, the liquid unit dosage forms of preparation contains active substance of the present invention and sterile carrier.According to carrier and concentration, this chemical compound can be suspended or dissolving.The preparation of solution is normally by being dissolved in active substance in a kind of carrier, and filter-sterilized before again it is packed into a kind of suitable bottle or the ampoule seals then.For example a kind of local anesthetic of adjuvant, antiseptic and buffer agent also can be dissolved in this carrier.In order to improve its stability, can be behind the bottle of packing into that this compositions is freezing, and under vacuum, water is removed, so just can obtain ejection preparation.
For oral solid formulation, can fill by mixing, the method that tabletting etc. are commonly used prepares solid oral composition.Mix that repeatedly active substance is distributed in those compositionss of a large amount of filleies of whole use, so just can obtain oral solid formulation.
For oral liquid, the present invention can be aqueous or oily suspensions, solution, Emulsion, syrup or elixir, perhaps can be a kind of available water before use or other suitable composite dry products of carrier, so just can obtain oral liquid.
Concrete preparation method:
It is to make like this that the present invention injects liquor: essence is got the Ginkgo total flavones extract and dipyridamole makes dissolving with an amount of water for injection according to quantity, add glycerol, add water for injection to 10000ml, adjust pH is 3.5-5.5, with the aseptic filtration of 0.22um microporous filter membrane, embedding, sterilization promptly get injection; The every ml of injection contains total flavonoids and should be 0.90～1.10mg, allowable error: answer≤3%; Dipyridamole should be 0～0.36mg, allowable error: answer≤3%.
Lyophilized injectable powder of the present invention is to make like this: essence is got the Ginkgo total flavones extract and dipyridamole makes dissolving with an amount of water for injection according to quantity, add water for injection and be diluted to 10000ml, adjust pH is 3.5-5.5, with the aseptic filtration of 0.22um microporous filter membrane, add the mannitol mixing, be distributed into 500, every 2ml, lyophilization, gland promptly gets lyophilized injectable powder; Lyophilized preparation total flavonoids content is whenever prevaricated and is no less than 2.0mg, allowable error: answer≤3%; Every of dipyridamole content is 0～0.72mg, allowable error: answer≤3%.
High capacity ejection preparation of the present invention is to make like this: essence is got the Ginkgo total flavones extract and dipyridamole dissolves with an amount of water for injection according to quantity, heating, adding 0.20%-0.50%767 type needle-use activated carbon while hot filters, the sodium chloride that filtrate adds final amount of liquid medicine 0.8-2.5% mixes, add water for injection simultaneously to 10000ml, adjust pH is 3.5-5.5, with the aseptic filtration of 0.22um microporous filter membrane, stirring makes mix homogeneously, and packing, sterilization promptly get the high capacity ejection preparation; The every ml of bulk capacity injection contains total flavonoids and should be 0.90～1.10mg, allowable error: answer≤3%; Dipyridamole should be 0～0.36mg, allowable error: answer≤3%.
Oral solutions of the present invention is to make like this: take by weighing Ginkgo total flavones extract and dipyridamole mix homogeneously according to quantity, add an amount of pure water and make dissolving, other gets an amount of sucrose and adds and make dissolving in the water that boils evenly, filter, make simple syrup,, add purified water to 10000ml with making final sugar content 20-60% in an amount of simple syrup adding said medicine, fill promptly gets oral liquid.
Capsule of the present invention is to make like this: take by weighing the abundant mix homogeneously of Ginkgo total flavones extract and dipyridamole according to quantity, add other adjuvants such as starch again, mix homogeneously promptly gets capsule.
More than prescription content obtains through science screening, and for especial patient, content that can corresponding adjustment dipyridamole increases or minimizing being no more than in the given scope, and its drug effect is constant.
Compared with prior art, the pharmaceutical preparation that can prevent and treat coronary heart disease, thrombotic disease provided by the invention, the inventor reduces the dipyridamole unit content in the prescription, effectively reduces the untoward reaction of this product, help strengthening the stability of product, aberration can not occur.Simultaneously, it is constant that the present invention keeps in the preparation Ginkgo total flavones unit content, only reduces the dipyridamole unit content, guaranteed the effectiveness of preparation, thereby reached purpose of the present invention.
For finishing the present invention, we have carried out a series of experiment, research:
Experiment 1: the clinical observation of injection untoward reaction of the present invention
Increasing clinical evidence shows, it is remarkable that Ginkgo Leaf Extract and Dipyridamole Injection is fastened plug property curative effect of disease to the treatment thrombosis, and the untoward reaction that it produces in therapeutic process has also brought very big misery to the patient, and we are from January, 2004 Ginkgo Leaf Extract and Dipyridamole Injection improvement prescription for this reason, reduced dipyridamole content, reduce untoward reaction, cooperate clinical observation, compare with Ginkgo Leaf Extract and Dipyridamole Injection, obtained comparatively satisfied effect, now the result has been announced as follows.
1 data and method
1.1 the physical data 1-12 month in 2004 is accepted patient's 245 examples altogether for medical treatment, male 151 examples, women 94 examples, age 32-62 year, myocardial infarction 71 examples wherein, angina pectoris 63 examples, cerebral thrombosis 56, thromboangiitis obliterans 55
1.2 group technology, medicine and treatment
The patient is divided into matched group 112 example and two groups of experimental group 133 examples; Medicine A: (every 1ml contains total flavonoids and should be 0.90～1.10 the injection for preparing according to the method for the invention, dipyridamole (C
24H
40N
8O
4) should be 0～0.36mg), medicine B: (every 1ml contains total flavonoids and should be 0.90～1.10mg the Ginkgo Leaf Extract and Dipyridamole Injection that company produces under the applicant, dipyridamole (C
24H
40N
8O
4) should be 0.36～0.44mg).Matched group 112 routine patients add normal saline 50ml intravenous drip (6-10min) with Ginkgo Leaf Extract and Dipyridamole Injection 10ml and use normal saline 500ml intravenous drip at last; Experimental group 133 routine patients use preparation 10ml of the present invention instead and add normal saline 50ml intravenous injection (6-10min), use normal saline 500ml intravenous drip at last.Two groups of patient's venipuncture conditions are all better, and guarantee that liquid does not have and exosmose.
2 results (statistical method: to two groups of results' relatively employing X
2Check) a situation arises sees Table 1 for two groups of untoward reaction.
Table 1 liang group adverse reaction rate is (example) relatively
| Group | The example number | Phlebalgia | Allergic rash | Feel sick | Uncomfortable in chest | Bring out asthma | The heart quivers | The total routine number of untoward reaction |
| Matched group | 133 | 6 | 5 | 6 | 5 | 2 | 4 | 28 |
| Experimental group | 112 | 1 | 0 | 0 | 1 | 0 | 0 | 2 |
| X 2 | 14.01 | 11.82 | 21.96 | 25.92 | 7.91 | 8.63 | 31.33 | |
| P | ＜0.01 | ＜0.01 | ＜0.01 | ＜0.01 | ＜0.01 | ＜0.01 | ＜0.01 |
The two groups of various untoward reaction example of patient number comparing differences all have significance, and matched group has 7 routine infants because of can not the Intolerance reaction being forced to drug withdrawal, and experimental group has 1 example, X
2=5.14, P＜0.01, difference has significance.Dermoreaction and the intravenous site of seeing experimental group thus wait untoward reaction obviously to reduce bitterly.
3 conclusions:
The result shows, is starkly lower than Ginkgo Leaf Extract and Dipyridamole Injection according to the untoward reaction rate of the injection (promptly reducing dipyridamole content) of the method for the invention preparation.
Experiment 2: the present invention improves the injection Experimental Study of Stability
Former Ginkgo Leaf Extract and Dipyridamole Injection is to adopt Folium Ginkgo extract and dipyridamole to make raw material, and by staying auspicious observation discovery, although before the deadline, content meets the pharmacopeia requirement, and color and luster changes often and maintains lower bound.We analyze influencing former injection stability factor, utilize orthogonal test to screen optimum prescription, and result of the test shows that this new choosing prescription stability improves, and tests as follows.
One, instrument and reagent
PHD-25 type acidometer (Shanghai analytical tool factory), electric-heated thermostatic water bath (Chongqing Medical Apparatus ﹠ Instrument Factory), injection of the present invention is by the inventive method preparation; Former Ginkgo Leaf Extract and Dipyridamole Injection is produced by our company.
Two, experimental technique and result
1, quadrature contrast test
Result with reference to interrelated data research has drafted three factors, and each factor is selected three levels (table 1,2), presses L9 (3
4) Orthogonal Experiment and Design (table 3), it is as follows to influence injection stability factor discussion experiment of the present invention:
Table 1 factor level table
| Factor level | The A pH value | B Folium Ginkgo extract (g) | C dipyridamole consumption (g) |
| 1 2 3 | 1～3.5(2.8，3.1，3.4) 3.5～5.5(3.5，4.5，5.5) 5.5～9.0(5.6，7.2，9.0) | 0～9.0(3.0，5.0，7.0) 9～11.0(9.0，10.0，11.0) ＞11.0(13.0，17.0，21.0) | 0～3.6(3.0，3.3，3.6) 3.6～4.4(3.7，4.0，4.4) ＞4.4(4.5，4.9，5.3) |
Annotate: Folium Ginkgo extract calculates with total flavonoids.
Table 2 factor level table
| Factor level | The A pH value | B Folium Ginkgo extract (g) | C dipyridamole consumption (g) |
| 1 2 3 | 3.1 4.5 7.2 | 10.0 5.0 17.0 | 3.3 4.0 4.9 |
Annotate: Folium Ginkgo extract calculates with total flavonoids.
2 methods
(1) injection formula of the present invention
Prescription is seen the factor table, gets Folium Ginkgo extract and dipyridamole respectively, adds a certain amount of glycerol, and water for injection adds to 10000ml.
(2) test method
Form according to prescription, be equipped with injection by the orthogonal test numbering scheme, embedding is pacified in the bottle 100 ℃ in 5ml respectively, the sterilization of 30min flowing steam gets finished product, puts respectively and boils 2h in the water-bath, regularly take out respectively and place cold water, pH value, content, color and luster are measured in cooling rapidly.
Table 3 L9 (3
4) test arrangement and result of the test
| A | B | C | Content (%) | |
| 1 2 3 4 5 6 7 8 9 K1 | 3.3 3.3 3.3 4.5 4.5 4.5 7.2 7.2 7.2 257.13 | 10.0 5.0 17.0 10.0 5.0 17.0 0.0 5.0 17.0 275.75 | 1.8 4.0 4.9 4.0 4.9 1.8 4.9 1.8 4.0 284.1 | 93.45 83.12 80.56 92.07 96.43 97.02 90.19 93.63 81.35 |
| K2 K3 K1 K2 K3 R | 285.52 265.17 85.71 95.17 88.39 9.46 | 273.18 258.93 91.92 91.06 86.31 5.61 | 256.54 267.18 94.70 85.51 89.06 9.19 |
3 experimental results
Just testing the gained result carries out intuitive analysis and handles and to see Table 2.Can find out according to the R value: the primary and secondary of three factors is respectively A, C, B.From the R value of each row as can be seen: optimum level is A
2B
1C
1, promptly pH value is 4.5, the Folium Ginkgo extract consumption is 10.0g, the dipyridamole consumption is 3.3g, and promptly optimum prescription scope is: the Folium Ginkgo extract consumption is 9.0～11.0g, and the dipyridamole consumption is 0～3.6g, adjust pH is 3.5～5.5, and glycerol is an amount of, and water for injection adds to 10000ml; After promptly making injection, every ml contains total flavonoids the best and should be 0.90～1.10mg, and dipyridamole the best should be 0～0.36mg, and pH value the best is 3.5～5.5.
4 new, old prescription stability relatively
By new, old prescription preparation dipyridamole injection liquid, get finished product respectively, carry out accelerated test (100 ℃, heating 2h), measure content, color and luster, the results are shown in Table 3.
Table 3
Can find out that from table 3 stability of the present invention's prescription is apparently higher than the former prescription of corresponding specification.
Three, conclusion
Need increase when the injection poor stability of former prescription preparation, Workshop Production and throw the principal agent amount, and new recipe stability has improved, and does not need to increase the principal agent amount of throwing again, the corresponding production cost that reduced has improved product quality.
The specific embodiment:
Embodiments of the invention 1: injection
Take by weighing: Ginkgo total flavones extract (amounting to total flavonoids 10g) dipyridamole 3.3g glycerol 10g
Preparation technology is: essence is got the Ginkgo total flavones extract and dipyridamole makes dissolving with an amount of water for injection according to quantity, add glycerol and add water for injection to 10000ml, adjust pH is 3.5-5.5, and with the aseptic filtration of 0.22um microporous filter membrane, embedding, sterilization promptly get injection.The every ml of injection contains total flavonoids and should be 0.90～1.10mg, allowable error: answer≤3%; Dipyridamole should be 0～0.36mg, allowable error: answer≤3%.
Embodiments of the invention 2: injection
Take by weighing: Ginkgo total flavones extract (amounting to total flavonoids 9g) dipyridamole 3.0g glycerol 10g
Preparation technology is: essence is got the Ginkgo total flavones extract and dipyridamole makes dissolving with an amount of water for injection according to quantity, add glycerol and add water for injection to 10000ml, adjust pH is 3.5-5.5, and with the aseptic filtration of 0.22um microporous filter membrane, embedding, sterilization promptly get injection.
Embodiments of the invention 3: injection
Take by weighing: Ginkgo total flavones extract (amounting to total flavonoids 11g) dipyridamole 3.6g glycerol 10g
Preparation technology is: essence is got the Ginkgo total flavones extract and dipyridamole makes dissolving with an amount of water for injection according to quantity, add glycerol and add water for injection to 10000ml, adjust pH is 3.5-5.5, and with the aseptic filtration of 0.22um microporous filter membrane, embedding, sterilization promptly get injection.
Embodiments of the invention 4: freeze-dried powder
Take by weighing: Ginkgo total flavones extract (amounting to total flavonoids 10g) dipyridamole 3.3g mannitol 20g
Preparation technology is: essence is got the Ginkgo total flavones extract and dipyridamole makes dissolving with an amount of water for injection according to quantity, add water for injection and be diluted to 10000ml, adjust pH is 3.5-5.5, with the aseptic filtration of 0.22um microporous filter membrane, add the mannitol mixing, be distributed into 500, every 2ml, lyophilization, gland promptly gets lyophilized injectable powder; Lyophilized preparation total flavonoids content is whenever prevaricated and is no less than 2.0mg, allowable error: answer≤3%; Every of dipyridamole content is 0～0.72mg, allowable error: answer≤3%.
The embodiment of the invention 5: high capacity ejection preparation
Take by weighing: Ginkgo total flavones extract (amounting to total flavonoids 10g) dipyridamole 3.3g sodium chloride 100g
Preparation technology is: essence is got the Ginkgo total flavones extract and dipyridamole dissolves with an amount of water for injection according to quantity, heating, adding 0.20%-0.50% 767 type needle-use activated carbons while hot filters, the sodium chloride that filtrate adds final amount of liquid medicine 0.8-2.5% mixes, add water for injection simultaneously to 10000ml, adjust pH is 3.5-5.5, with the aseptic filtration of 0.22um microporous filter membrane, stirring makes mix homogeneously, and packing, sterilization promptly get the high capacity ejection preparation.The every ml of bulk capacity injection contains total flavonoids and should be 0.90～1.10mg, allowable error: answer≤3%; Dipyridamole should be 0～0.36mg, allowable error: answer≤3%.
Embodiments of the invention 6: oral liquid
Take by weighing: Ginkgo total flavones extract (amounting to total flavonoids 11g) dipyridamole 3.6g sucrose 4000g
Preparation technology is: take by weighing Ginkgo total flavones extract and dipyridamole mix homogeneously according to quantity, add an amount of pure water and make dissolving, other gets an amount of sucrose and adds and make dissolving in the water that boils evenly, filter, make simple syrup,, add purified water to 10000ml with making final sugar content 20-60% in an amount of simple syrup adding said medicine, fill promptly gets oral liquid.
Embodiments of the invention 7: capsule
Take by weighing: Ginkgo total flavones extract (amounting to total flavonoids 11g) dipyridamole 3.6g starch 1000g sodium carboxymethyl cellulose 100g
Preparation technology is: take by weighing the abundant mix homogeneously of Ginkgo total flavones extract and dipyridamole according to quantity, add starch, sodium carboxymethyl cellulose, mix homogeneously promptly gets capsule.
Claims (9)
1, the pharmaceutical preparation of a kind of prevention and treatment coronary heart disease, thrombotic disease, it is characterized in that: the preparation that Folium Ginkgo extract and dipyridamole are mixed and made into is by cubage: every preparation unit contains total flavonoids and should be 0.90～1.10mg, dipyridamole should be 0～0.36mg, and wherein ejection preparation is in every ml unit content.Also contain additives in the preparation.
2, according to the pharmaceutical preparation of the described prevention of claim 1 and treatment coronary heart disease, thrombotic disease, it is characterized in that: described preparation comprises injection preparation, oral liquid, oral liquid solid preparation.Wherein injection preparation comprises: injection liquor, freeze-dried powder, powder injection formulation, high capacity ejection preparation and oral formulations: comprise oral liquid, capsule, tablet or pill.
3, the preparation method of the pharmaceutical preparation of prevention described in claim 1 or 2 and treatment coronary heart disease, thrombotic disease, it is characterized in that: calculate according to the preparation unit content, essence is got Ginkgo total flavones extract and dipyridamole mix homogeneously respectively, add different adjuvants again, make different products with different conventional methods.
4, according to the preparation method of the pharmaceutical preparation of the described prevention of claim 3 and treatment coronary heart disease, thrombotic disease, it is characterized in that: essence is got the Ginkgo total flavones extract and dipyridamole makes dissolving with an amount of water for injection according to quantity, add glycerol and add water for injection to 10000ml, adjust pH is 3.5-5.5, with the aseptic filtration of 0.22um microporous filter membrane, embedding, sterilization promptly get injection; The every ml of injection contains total flavonoids and should be 0.90～1.10mg, allowable error: answer≤3%; Dipyridamole should be 0～0.36mg, allowable error: answer≤3%.
5, according to the preparation method of the pharmaceutical preparation of the described prevention of claim 3 and treatment coronary heart disease, thrombotic disease, it is characterized in that: essence is got the Ginkgo total flavones extract and dipyridamole makes dissolving with an amount of water for injection according to quantity, add water for injection and be diluted to 10000ml, adjust pH is 3.5-5.5, with the aseptic filtration of 0.22um microporous filter membrane, add the mannitol mixing, be distributed into 500, every 2ml, lyophilization, gland promptly gets lyophilized injectable powder; Lyophilized preparation total flavonoids content is whenever prevaricated and is no less than 2.0mg, allowable error: answer≤3%; Every of dipyridamole content is 0～0.72mg, allowable error: answer≤3%.
6, according to the preparation method of the pharmaceutical preparation of the described prevention of claim 3 and treatment coronary heart disease, thrombotic disease, it is characterized in that: essence is got the Ginkgo total flavones extract and dipyridamole dissolves with an amount of water for injection according to quantity, heating, adding 0.20%-0.50%767 type needle-use activated carbon while hot filters, the sodium chloride that filtrate adds final amount of liquid medicine 0.8-2.5% mixes, add water for injection simultaneously to 10000ml, adjust pH is 3.5-5.5, with the aseptic filtration of 0.22um microporous filter membrane, stirring makes mix homogeneously, and packing, sterilization promptly get the high capacity ejection preparation; Among the present invention, also can add additives.The every ml of bulk capacity injection contains total flavonoids and should be 0.90～1.10mg, allowable error: answer≤3%; Dipyridamole should be 0～0.36mg, allowable error: answer≤3%.
7, according to the preparation method of the pharmaceutical preparation of the described prevention of claim 3 and treatment coronary heart disease, thrombotic disease, it is characterized in that: take by weighing Ginkgo total flavones extract and dipyridamole mix homogeneously according to quantity, add an amount of pure water and make dissolving, other gets an amount of sucrose and adds and make dissolving in the water that boils evenly, filters, and makes simple syrup, to make final sugar content 20-60% in an amount of simple syrup adding said medicine, add purified water to 10000ml, fill promptly gets oral liquid.
8, according to the preparation method of the pharmaceutical preparation of right 3 described preventions and treatment coronary heart disease, thrombotic disease, it is characterized in that: take by weighing the abundant mix homogeneously of Ginkgo total flavones extract and dipyridamole according to quantity, add other adjuvants such as starch again, mix homogeneously promptly gets capsule.
9, according to the preparation method of the pharmaceutical preparation of the described prevention of claim 3 and treatment coronary heart disease, thrombotic disease, it is characterized in that: the described carrier of injection preparation is selected from: cosolvent, analgesic, regulate the osmotic pressure agent, PH regulator, filler, solvent for injection, antiseptic, antioxidant, protective agent; The described carrier of oral formulations is selected from: sweeting agent, binding agent, filler, diluent, tablet agent, lubricant, disintegrating agent, coloring agent, correctives and wetting agent, can carry out coating to tablet in case of necessity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610051010 CN1895298A (en) | 2006-04-18 | 2006-04-18 | Medicinal preparation for treating and preventing coronary heart disease and thromboembolia disease and its preparation |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610051010 CN1895298A (en) | 2006-04-18 | 2006-04-18 | Medicinal preparation for treating and preventing coronary heart disease and thromboembolia disease and its preparation |
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| CN1895298A true CN1895298A (en) | 2007-01-17 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670671A (en) * | 2012-06-12 | 2012-09-19 | 湖北济生医药有限公司 | Ginkgo-dipyridamole medicine combination and preparation method thereof |
| CN102793730A (en) * | 2012-08-31 | 2012-11-28 | 山西普德药业股份有限公司 | Ginkgo-damole medicinal composition and preparation method thereof |
| RU2823161C1 (en) * | 2023-11-10 | 2024-07-18 | федеральное государственное автономное образовательное учреждение высшего образования Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский университет) (ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Се | Method of treating pulmonary artery thromboembolism by ultrasound-assisted systemic thrombolytic therapy |
-
2006
- 2006-04-18 CN CN 200610051010 patent/CN1895298A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670671A (en) * | 2012-06-12 | 2012-09-19 | 湖北济生医药有限公司 | Ginkgo-dipyridamole medicine combination and preparation method thereof |
| CN102670671B (en) * | 2012-06-12 | 2014-09-17 | 湖北济生医药有限公司 | Ginkgo-dipyridamole medicine combination and preparation method thereof |
| CN102793730A (en) * | 2012-08-31 | 2012-11-28 | 山西普德药业股份有限公司 | Ginkgo-damole medicinal composition and preparation method thereof |
| CN102793730B (en) * | 2012-08-31 | 2013-11-06 | 山西普德药业股份有限公司 | Ginkgo-damole medicinal composition and preparation method thereof |
| RU2823161C1 (en) * | 2023-11-10 | 2024-07-18 | федеральное государственное автономное образовательное учреждение высшего образования Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский университет) (ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Се | Method of treating pulmonary artery thromboembolism by ultrasound-assisted systemic thrombolytic therapy |
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