CN1927346B - Mailuoning injection and preparation thereof - Google Patents
Mailuoning injection and preparation thereof Download PDFInfo
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- CN1927346B CN1927346B CN2005100150048A CN200510015004A CN1927346B CN 1927346 B CN1927346 B CN 1927346B CN 2005100150048 A CN2005100150048 A CN 2005100150048A CN 200510015004 A CN200510015004 A CN 200510015004A CN 1927346 B CN1927346 B CN 1927346B
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- filtrate
- ethanol
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- filter
- injection
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- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a arteries and veins carbamazepine injection product and its preparation methods. After the active component of the dendrobium, achyranthis, figwort root, honeysuckle flower are extracted according to weight rate with equivalent ratio, add mannitol and PVP, ultrafiltrate, adjust pH, aseptic filter, bung, freeze-dry and the freeze-dried powder is obtained; or after sterilization seal gland and the injection is got. The preparation process of effective components is: after the honeysuckle is percolated extracted with ethanol it is purified by the ethyl acetate, achyranthis, figwort root, and honeysuckle flower are soaked with ethanol, and then are purified with the macroporous resin after the backstreaming extraction.
Description
Technical field
The present invention relates to a kind of is the ejection preparation of active component with the Chinese medicine compound extract, particularly, is a kind of 'Mailuoning ' injection preparation and preparation method thereof.
Background technology
MAILUONING ZHUSHEYE is the Chinese medicine compound injection that develops on the basis of famous hospital " SIMIAOYONGAN TANG ", form by Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii, Flos Lonicerae four flavor Chinese medicines, be widely used in thromboangiitis obliterans, arteriosclerosis obliterans, cerebral thrombosis and sequela, multiple takayasu arteritis, acute limb Arteriae embolization, diabetic gangrene, venous thrombosis and thrombophlebitis etc.But the report of untoward reaction in recent years increasing (Luo Zhihua, Jiang Sanyuan. Chinese medicine and clinical .2002,2 (6): 412-413; .70 such as Chen Aiqun example MAILUONING ZHUSHEYE untoward reaction document analysis. adverse effect magazine .2003,2:162-165.), concentrate on many aspects such as skin lesion, acute respiration are embarrassed, throat spasm, anaphylactic shock, headache, microcirculation disturbance, angina pectoris, trembling of limbs, lumbago, edema, renal failure.
Chinese patent CN1078148A discloses the production method of MAILUONING ZHUSHEYE, and this method adopts decoction and alcohol sedimentation technique that four kinds of medical materials are extracted simultaneously, and then gets effective ingredient with ethyl acetate extraction.There is following several respects defective in said method:
1. it is more to adopt water extraction to extract when respectively distinguishing the flavor of the medical material effective ingredient in the prescription water-solubility impurity stripping, though alcohol precipitation process part that can be removed impurity afterwards is thorough inadequately;
2. only adopt ethyl acetate to carry out purification after four flavor Chinese medicine mixing waters are carried, purification effect is not thorough;
3. solution directly carries out preparation process behind the ethyl acetate purification, does not further remove macromolecular substances such as resin, albumen, tannin.
More than analyze as can be seen, existing 'Mailuoning ' injection preparation preparation technology is backward, extensive, makes active constituent content not high on the one hand, makes heterologous impurity can not get effective control on the one hand, so the occurrence frequency of untoward reaction is more and more higher.And also there is problem of unstable in aqueous injection in transportation, storage.
Therefore, it is significant in clinical to develop safer, effective, stable 'Mailuoning '.
Summary of the invention
One of purpose of the present invention is at the deficiencies in the prior art, according to the different physicochemical property of medicine of respectively distinguishing the flavor of in the prescription, adopts diverse ways to extract, and separates, and is refining, and a kind of safe, effective, stable 'Mailuoning ' injection preparation is provided.
Another object of the present invention provides the preparation method of this 'Mailuoning ' injection preparation.
The present invention realizes by following technical scheme:
'Mailuoning ' injection preparation of the present invention comprises that by Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii, Flos Lonicerae be acceptable carrier in the extract that makes of raw material and the ejection preparation.Preferably, described extract by Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii and Chinese medicine honeysuckle according to 1: 1: 1: 1 weight portion proportioning is extracted and is made; Described carrier is selected from one or both among mannitol, lactose, sucrose and the PVP.More preferably, described crude drug and carrier have following weight portion proportioning: Radix Achyranthis Bidentatae 900 Radix Scrophulariaes 900 Herba Dendrobiis 900 Flos Loniceraes 900 mannitol 53 PVP 1.
'Mailuoning ' of the present invention can be made injection, lyophilized injectable powder and infusion solution; Preferred injection and lyophilized injectable powder; The best is a lyophilized injectable powder.
The preparation method of 'Mailuoning ' injection preparation of the present invention may further comprise the steps:
(1) Flos Lonicerae powder of getting recipe quantity is broken into coarse powder, crosses sieve No. 2, uses ethanol percolate extraction, percolate filters, and subsequent filtrate reclaims ethanol, and concentrating under reduced pressure becomes extractum, centrifugal removal insoluble impurities adds water, fully stirs, standing over night is filtered, and filtrate decompression is condensed into extractum, filter, remove precipitation, hydrochloric acid is regulated pH value, ethyl acetate extraction, combining extraction liquid reclaims the dry extract I that gets of ethyl acetate final vacuum;
(2) Radix Achyranthis Bidentatae, Herba Dendrobii, the Radix Scrophulariae of getting recipe quantity pulverized back with reflux, extract, after the soak with ethanol, merge extractive liquid,, filter, filtrate decompression is condensed into extractum, adds entry and fully stirs, standing over night, filter macroporous adsorbent resin on the filtrate, water, 25% ethanol, 75% ethanol elution respectively, collect eluent, reclaim ethanol concentrating under reduced pressure and vacuum drying and get extract II;
(3) will add the heating of injection water after extract I and the extract II merging, dissolving is put cold naturally, cold preservation 24h filters, and it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collect ultrafiltrate, the cold preservation after-filtration that spends the night adds mannitol and PVP in the filtrate, filter, filtrate is added water for injection to recipe quantity, adjust pH 5.5～7.0, aseptic filtration, filtrate are sub-packed in the cillin bottle, jump a queue, lyophilization, packing gets lyophilized injectable powder; Or the sterilization rear seal-cover, packing gets injection.
Preferably, the preparation method of 'Mailuoning ' injection preparation of the present invention may further comprise the steps:
(1) Flos Lonicerae powder of getting recipe quantity is broken into coarse powder, cross sieve No. 2, with 50～95% ethanol percolate extraction of 8～16 times of amounts, 10～40h percolation finishes, and percolate filters, subsequent filtrate reclaims ethanol, being evaporated to relative density is the extractum of 1.05～1.30 (50 ℃), and centrifugal removal insoluble impurities adds 4～8 times of water gagings, fully stir, standing over night is filtered, and filtrate decompression is concentrated into the extractum that relative density is 1.05～1.25 (50 ℃), filter, remove precipitation, 10%～30% hydrochloric acid is regulated pH value to 2～6, ethyl acetate extraction 2～6 times, combining extraction liquid, 60 ℃ of vacuum dryings get extract I after the recovery ethyl acetate;
(2) Radix Achyranthis Bidentatae, Herba Dendrobii, Radix Scrophulariae of getting recipe quantity pulverized the back with reflux, extract, behind 50%～90% soak with ethanol, 1～3h 2～3 times, each 1～3h, merge extractive liquid,, filter, filtrate decompression is concentrated into the extractum that relative density is 1.05～1.20 (50 ℃), the water that adds 4～6 times of amounts fully stirs, standing over night, filter, Semi-polarity or strong polar macroporous adsorption resin on the filtrate, use 2 times of bed volume water, 2 times of bed volume 25% ethanol, 2 times of bed 75% ethanol elutions respectively, collect 75% ethanol elution, reclaim ethanol concentrating under reduced pressure and 60 ℃ of vacuum drying extract II;
(3) will extract I and extract II add injection water heated and boiled 8～15 minutes after merging, put naturally cold, cold preservation 24h, filter, it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collects ultrafiltrate, the cold preservation after-filtration that spends the night adds the mannitol and the PVP of recipe quantity in the filtrate, filter, filtrate is added water for injection to recipe quantity, adjust pH 6.5～7.0, aseptic filtration, filtrate is sub-packed in the cillin bottle, jumps a queue lyophilization, packing gets lyophilized injectable powder; Or the sterilization rear seal-cover, packing gets injection.
More preferably, the preparation method of 'Mailuoning ' injection preparation of the present invention may further comprise the steps:
(1) Flos Lonicerae powder of getting recipe quantity is broken into coarse powder, cross sieve No. 2, with 80% ethanol percolate extraction of 12 times of amounts, the 20h percolation finishes, percolate filters, subsequent filtrate reclaims ethanol, and concentrating under reduced pressure (temperature≤70 ℃) to relative density is the extractum of 1.20 (50 ℃), centrifugal removal insoluble impurities, add 6 times of water gagings, fully stir, standing over night is filtered, it is the extractum of 1.15 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), filter, remove precipitation, filtrate is determined volume, 20% hydrochloric acid is regulated pH value to 2, equal-volume ethyl acetate extraction 6 times, combining extraction liquid, 60 ℃ of vacuum dryings get extract I after the recovery ethyl acetate;
(2) get the Radix Achyranthis Bidentatae of recipe quantity, Herba Dendrobii, Radix Scrophulariae is pulverized the back with reflux, extract, behind the 70% soak with ethanol 1.5h 2 times, each 2h, add for the first time 8 times of amounts, add for the second time 6 times of amounts, merge extractive liquid,, filter, it is the extractum of 1.15 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), the water that adds 5 times of amounts fully stirs, and standing over night is filtered, AB-8 or SA-1 macroporous adsorbent resin on the filtrate, use 2 times of bed volume water rinse resins respectively, 2 times of bed volume 25% alcohol flushing impurity, 2 times of bed 75% ethanol elutions are collected 75% ethanol elution, reclaim ethanol concentrating under reduced pressure and 60 ℃ of vacuum drying extract II;
(3) will extract I and extract II add injection water heated and boiled 10 minutes after merging, put naturally cold, cold preservation 24h, filter, it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collects ultrafiltrate, the cold preservation after-filtration that spends the night adds the mannitol and the PVP of recipe quantity in the filtrate, filter, filtrate is added water for injection to recipe quantity, adjust pH 6.5～7.0, aseptic filtration, filtrate is sub-packed in the cillin bottle, jumps a queue lyophilization, packing gets lyophilized injectable powder; Or the sterilization rear seal-cover, packing gets injection.
Wherein, the preferred SA-1 type of the macroporous adsorbent resin macroporous adsorbent resin described in the step (2).
Best, 'Mailuoning ' injection preparation of the present invention is an injectable powder, and its prescription and preparation method are:
Prescription:
Radix Achyranthis Bidentatae 4500g Radix Scrophulariae 4500g Herba Dendrobii 4500g Flos Lonicerae 4500g mannitol 265g PVP 5g
Preparation method:
(1) Flos Lonicerae powder of getting recipe quantity is broken into coarse powder, cross sieve No. 2, with 80% ethanol percolate extraction of 12 times of amounts, the 20h percolation finishes, percolate filters, subsequent filtrate reclaims ethanol, and concentrating under reduced pressure (temperature≤70 ℃) to relative density is the extractum of 1.20 (50 ℃), centrifugal removal insoluble impurities, add 6 times of water gagings, fully stir, standing over night is filtered, it is the extractum of 1.15 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), filter, remove precipitation, filtrate is determined volume, 20% hydrochloric acid is regulated pH value to 2, equal-volume ethyl acetate extraction 6 times, combining extraction liquid, 60 ℃ of vacuum dryings get extract I after the recovery ethyl acetate;
(2) get the Radix Achyranthis Bidentatae of recipe quantity, Herba Dendrobii, Radix Scrophulariae is pulverized the back with reflux, extract, behind the 70% soak with ethanol 1.5h 2 times, each 2h, add for the first time 8 times of amounts, add for the second time 6 times of amounts, merge extractive liquid,, filter, it is the extractum of 1.15 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), the water that adds 5 times of amounts fully stirs, and standing over night is filtered, AB-8 or SA-1 macroporous adsorbent resin on the filtrate, use 2 times of bed volume water rinse resins respectively, 2 times of bed volume 25% alcohol flushing impurity, 2 times of bed 75% ethanol elutions are collected 75% ethanol elution, reclaim ethanol concentrating under reduced pressure and 60 ℃ of vacuum drying extract II;
(3) injection water 2000ml will be added after extract I and the extract II merging, heated and boiled 10 minutes, naturally put coldly, cold preservation 24h filters, it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collect ultrafiltrate 3000ml, the cold preservation after-filtration that spends the night adds the mannitol and the PVP of recipe quantity in the filtrate, filter, filtrate is added water for injection to 3500ml, adjust pH to 6.5～7.0, aseptic filtration, filtrate is sub-packed in the 7ml cillin bottle, every bottle of 3.5ml jumps a queue, lyophilization, packing gets lyophilized injectable powder; Or the sterilization rear seal-cover, packing gets injection.
'Mailuoning ' injection preparation of the present invention is the result of a large amount of scientific experimentss, and the extracting method of every kind of medical material and preparation process are all through testing repeatedly and verifying.Science below by concrete test explanation preparation method of the present invention.
Flos Lonicerae extract preparation technology's research
1. experimental technique:
Flos Lonicerae is crossed pulverizer break into coarse powder, accurately take by weighing two parts, every part of 100g.12 times of water gaging reflux, extract, twice of sample 1 usefulness stir reflux, extract, 3h down with 7 times of amounts for the first time, and inclining supernatant; The 5 times of amounts that medicinal residues add for the second time stir reflux, extract, 2h down, and inclining supernatant; Merge the secondary aqueous extract, determine that HPLC behind the volume measures the concentration of chlorogenic acid.12 times of amounts of sample 2 usefulness, 75% ethanol percolation, percolate is determined volume, HPLC measures the concentration of chlorogenic acid.
2. result:
Two groups of experiment extracting solution are measured the concentration of volume and chlorogenic acid, calculate the amount of chlorogenic acid, and calculate extraction ratio.Get extracting solution 20ml and put evaporate to dryness in the evaporating device, vacuum drying is weighed, and calculates the amount of the total gained solid content of every kind of extracting method.The results are shown in Table 1.
The extraction ratio of two kinds of extracting method active ingredient chlorogenic acids of table 1
As can be seen from Table 1, the extraction ratio of ethanol percolate extraction is higher than the total extraction ratio of water extraction, and the amount of gained solid content also is lower than water extraction, so, be better than water extraction with the method for ethanol extraction Flos Lonicerae.
Radix Achyranthis Bidentatae, Radix Scrophulariae and Herba Dendrobii extract preparation technology's research
1. experimental technique:
Respectively Radix Achyranthis Bidentatae and Herba Dendrobii are ground into coarse powder, the 100g uniform mixing is respectively got in the Radix Scrophulariae section, takes by weighing 2 parts.The water reflux, extract, twice of 14 times of amounts of sample 1 usefulness with the water logging bubble 2h of 8 times of amounts, stirs reflux, extract, 3h down for the first time then, and inclining supernatant; The water that medicinal residues add 6 times of amounts for the second time stirs reflux, extract, 2h down, and inclining supernatant; Merge aqueous extract twice, determine that HPLC behind the volume measures the concentration of cinnamic acid, oleanolic acid type saponin, escoparone.Sample 2 is used 80% ethanol extraction instead with the method operation, determines volume behind the merging extracted twice liquid, and HPLC measures the concentration of cinnamic acid, oleanolic acid type saponin, escoparone.
2. result:
Two groups of experiment extracting solution are measured the concentration of volume and cinnamic acid, oleanolic acid type saponin, escoparone, the amount of parameter composition, and calculate extraction ratio.Get extracting solution 20ml and put evaporate to dryness in the evaporating device, vacuum drying is weighed, and calculates the amount of the total gained solid content of every kind of extracting method.The results are shown in Table 2.
The extraction ratio of two kinds of extracting method index components of table 2
As can be seen from Table 2, the extraction ratio of three index components ethanol extractions all is higher than the total extraction ratio of water extraction, and the amount of gained solid content also is lower than water extraction, so, be better than water extraction with the method for ethanol extraction Radix Achyranthis Bidentatae, Radix Scrophulariae and Herba Dendrobii.
The rational research of ultrafiltration technology
1. experimental technique:
Get and pulverize back Radix Achyranthis Bidentatae figwort, dendrobium stem extract 4g, Flos Lonicerae extract 15g, uniform mixing are designated as sample 1.Same operation is got two parts again, is designated as sample 2 samples 3 respectively.Add injection water 200ml respectively, respectively heated and boiled is 10 minutes, puts coldly naturally, and cold preservation 24h after-filtration, filtered solution mistake molecular cut off respectively are 3000 ultrafilter membrane ultrafiltration, collect ultrafiltrate 300ml respectively.The HPLC method is measured cinnamic acid in the ultrafiltrate, the concentration of oleanolic acid type saponin, escoparone.Precision is measured ultrafiltrate 20ml and is dried in the water-bath to the evaporating dish respectively, dries by the fire 3h in 105 ℃ of baking ovens, takes out the back and places half an hour in the exsiccator, weighs.
2, result:
Calculate the rate of transform and the solid content yield of ultrafiltration front and back cinnamic acid, oleanolic acid type saponin, escoparone, the results are shown in Table 3.
The rate of transform and the solid content yield of index components before and after table 3 ultrafiltration
Solution before and after the ultrafiltration detects resin, tannin, protein item according to official method respectively, the results are shown in Table 4.
Test item result's contrast before and after table 4 ultrafiltration
By result of the test as can be seen, color and luster obviously improves after the ultrafiltration, and ultrafiltration can be gone out most resins, tannin, protein impurities.The rate of transform of index components is all higher as can be seen from Table 4, therefore can determine that ultrafiltration is necessary.
Determining of freeze-drying curve
1. experimental technique:
Get and pulverize back Radix Achyranthis Bidentatae figwort, dendrobium stem extract 4g, Flos Lonicerae extract 15g, uniform mixing add injection water 200ml, heated and boiled 10 minutes, put naturally cold, cold preservation 24h after-filtration, it is 3000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, collects ultrafiltrate 300ml.Add mannitol 26.5g in the ultrafiltrate, PVP0.5g filters, and filtrate is added water for injection to 350ml.Transfer PH to 6.5-7.0, degerming filters, filtrate is sub-packed in the 7ml cillin bottle, every bottle of 3.5ml, sample moves in the freeze drying box, sample temperature probe and mensuration electrode are divided in 3 sample bottles of insertion, fridge is lowered the temperature with 20 ℃/hour speed, treat that sample thaws back (observe from form, sample is color and luster, the uniform crystal column of quality) fully, stops compressor, and begin to lower the temperature, the temperature that makes dividing plate rises with 10 ℃/hour speed, temperature and the baffle temperature and the corresponding resistance of record sample, eutectic point be :-21 ℃.
2, result:
Determine freeze-drying curve through the test of lyophilization repeatedly, concrete parameter sees the following form.
| Time (hour) | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 |
| Baffle temperature (℃) | 30 | -20 | -8 | -40 | -40 | -40 | -40 | -40 | -25 | -20 | 25 | 7.5 | 10 | 12.5 | 15 | 15 |
| Sample temperature (℃) | 25 | -5 | -5 | -35 | -36 | -38 | -38 | -38 | -36 | -35 | -31 | -30 | -28 | -27 | -25 | -25 |
| Time (hour) | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | 24 | 25 | 26 | 27 | 28 | 29 | 30 | |
| Baffle temperature (℃) | 15.2 | 15.2 | 20 | 20 | 30 | 31 | 31 | 35 | 35 | 35 | 40 | 40 | 40 | 40 | 40 | |
| Sample temperature (℃) | -22 | -20 | -15 | -15 | -10 | -8 | -4 | -1 | 10 | 30 | 35 | 35 | 35 | 35 | 35 |
'Mailuoning ' injection preparation of the present invention has following beneficial effect:
1. according to the physicochemical property of each single medicinal material in the prescription, adopt the method for alcohol extracting-water precipitating to extract respectively, improved content of effective;
2. according to the physicochemical property of each single medicinal material in the prescription, adopt the method for ethyl acetate and macroporous resin refining respectively, be further purified effective ingredient;
3. the ultrafiltration step in the preparation process is removed impurity to the full extent, thereby has guaranteed the safe, effective, stable of final products.
Description of drawings
Fig. 1 is the freeze-drying curve figure of medicine freeze dried Mailuoning powder of the present invention
For a better understanding of the present invention, below by experiment the example further set forth the useful effect of invention medicine, experimental example comprises drug effect animal experiment and the stability study of medicine of the present invention. Test is intended to further illustrate the effect of medicine of the present invention below, but not limitation of the present invention. The invention medicine that this experimental example adopts is to be prepared from by embodiment 4.
The treatment effect of one pair of intraluminal middle cerebral artery occlusion in rats bolt of experimental example line method focal brain ischemia-reperfusion injury model
Receive in the limb in face of the offside through the rat anesthesia of cerebral infarction plug clear-headed appearance, the shoulder inward turning, flesh tension force descends, and pushes away right shoulder to side shifting, and resistance reduces, even some animal also occurs ceaselessly to the side hemiplegia sample symptoms such as phenomenon of turn-taking. The rat of survival in 24 hours is carried out the neurology scoring, and train of thought rather organizes rat and model group compares, and the behavior obstacle of rat obviously improves (p＜0.01): the brain water content of the peaceful height of train of thought, middle dosage group is starkly lower than model group (p＜0.01); Brain tissue infraction degree obviously reduced after the TTC coloration result showed medication group cerebral ischemia re-pouring 24h, observes brain tissue and mainly be the ischemic change under light microscopic, significantly softening kitchen range occurred, rather organized rat cerebral tissue's degree of ischemia through train of thought and alleviated, and reduced softening kitchen range.
The complete cerebral ischemia re-pouring injured protective effect of two pairs of pallasiomys of experimental example
Full cerebral ischemic model group murine brain water content is obviously in the art group of doing evil through another person, the peaceful medication height of train of thought, and middle dosage group and model group contrast be variant remarkable (p＜0.01) all; Model group brain tissue SOD is movable obviously to be reduced, and MDA content obviously improves, peaceful each the dosage group of train of thought and the more then active obviously raising of SOD of model control group, MDA content significantly descend (p＜0.05); Pathological examination shows that model group 6 examples are seen the special mess infarcted region, the visible cell karyopycnosis, dyeing is deepened, and kernel is unclear, and the hippocampus nerve cell obviously reduces, arrangement disorder, cell volume diminishes, and form is irregular, and the pyknosis of part karyon is dyed deeply, kernel disappears, the kytoplasm inequality, cavity appears in the part cell, separates between cell. Train of thought peaceful medication group neuron and brain parenchymal cell structure are substantially normal, have no the infarct kitchen range, the karyopycnosis of part sample visible cell, and dyeing is deepened, and kernel is unclear, and varied number and degree are obviously light than model group.
The impact of three pairs of focal cerebral ischemias of experimental example (MCAO) rat brain blood flow amount
Model control group rat cerebral embolism Cerebral Blood Flow Following obviously reduces, drop to original 51.3% behind the MCAO10min, continue afterwards to descend, but each time point fall and 10min no significant difference, each administration amount group shows, its brain blood flow value is than the obvious increase of model group (p＜0.05) behind the MACO, and is the most obvious with the peaceful high dosage of train of thought, shows that train of thought rather can obviously increase the brain blood flow amount of rat behind the MCAO.
Experimental example four function of promoting blood circulation to disperse blood clots
The rabbit blood platelet that train of thought is rather induced ADP is assembled obvious inhibitory action, increase inhibitory action along with dosage between 0.1ml～0.4g/ml dosage strengthens gradually, and namely its rabbit blood platelet that ADP is induced inhibitory action of assembling has obvious dosage dependence; Peaceful three dosage of train of thought all can obviously suppress rat suppository formation during anti-thrombosis was tested in the body; Peaceful three dosage of train of thought all have the effect in obvious prolongation clotting time. After rat gave the peaceful 3d of train of thought, each dosage group was similar to the effect of compound injection of red sage root, and the fibrin ferment time is obviously prolonged, and factor time and partial thromboplastin time also significantly prolong, and reduced the fibrin original content.
Experimental example five acute toxicity tests
After train of thought is rather pressed the administration of the former crude drug body weight of 338g/kg mouse stomach, twice on the one, activity, feed intake reduce behind for the second time administration 30min, recovered afterwards normal on the 2nd day, have no other abnormal responses, continuous 7 days interim other the obvious toxic reactions that have no of observation afterwards, none animal dead, average weight increases 1.21g, anatomic observation, and each animal main organs does not have the visible pathology of naked eyes. Integral dose 676g/kg, maximum dosage-feeding are equivalent to more than 1127 times of clinical consumption.
Experimental example six rat chronic toxicity tests
Train of thought is peaceful, and three dosage of continuous 90 days gastric infusion 120.0 60.0 12.0g/kg crude drugs of rat, control group are given distilled water, and stops 15 days convalescences of observation post administration.
Administration is 90 days continuously, and the outward appearance sign of three dosage treated animals, behavioral activity do not have obviously unusual, and the feed day consumption increases with body weight, and each treated animal does not have obvious difference to feed consumption. (0 day) ratio before administration 90 days and the administration, weight average increases: heavy dose of 151.93g, middle dosage 117.36g, low dose of 152.13g, control group 157.9g. Administration 90 days, large, medium and small dosage group peripheral hemogram Index for examination and the equal no difference of science of statistics of control group, 10 indexs of blood biochemistry checking, heavy dose of group T-bil and control group relatively have significant difference (p＜0.05), other blood biochemistry checkings, data all fluctuate in normal scope, stop medicine and observe 15 days, have no unusual. Each treated animal of anatomic observation except have the individual animal lung tissue have naked eyes as seen unusually, other is organized does not all have the visible pathology of naked eyes; 90 days big or middle dosage group liver coefficients of administration and small dose group and control group be p＜0.05 relatively, relatively equal no difference of science of statistics between other each liver coefficient sets; Stop also no difference of science of statistics of medicine 15 days. Histopathological examination, heavy dose of group and the control group heart, liver, spleen, lung, kidney, brain (cerebellum), sexual gland (testis, prostate, uterus, ovary), thyroid gland, thymus gland, pancreas, adrenal gland, stomach, upper duodenum 12, time, colon, lymph node etc. Administration 90 days, each internal organs does not all have form more than 15 days, structure changes to stop medicine.
Experimental example six stability tests
1. method: three batches of freeze dried Mailuoning powder samples (lot number is respectively 030515,030521,030526) are placed with packing (being equivalent to the pharmaceutical packing of going on the market in packaging material quality and structure) room temperature with clinical testing, investigate 12 months continuously, observe its variation situation, get its mean value.
2. result: the results are shown in Table 5.
Table 5 three batch sample results of stability
Medicine of the present invention is to be prepared from by following examples, and following specific embodiment is explanation of the invention, can not limit the present invention.
The specific embodiment
Embodiment 1: the preparation of freeze dried Mailuoning powder
(1) extracting honeysuckle 1500g is ground into coarse powder, cross sieve No. 2, with 50 ethanol percolate extraction of 8 times of amounts, the 15h percolation finishes, and percolate filters, subsequent filtrate reclaims ethanol, being evaporated to relative density is the extractum of 1.05 (50 ℃), and centrifugal removal insoluble impurities adds 4 times of water gagings, fully stir, standing over night is filtered, and filtrate decompression is concentrated into the extractum that relative density is 1.15 (50 ℃), filter, remove precipitation, 10% hydrochloric acid is regulated pH value to 2.5, equal-volume ethyl acetate extraction 4 times, combining extraction liquid, 60 ℃ of vacuum dryings get extract I after the recovery ethyl acetate;
(2) get each 1500g of Radix Achyranthis Bidentatae, Herba Dendrobii, Radix Scrophulariae and pulverize the back with reflux, extract, behind the 60% soak with ethanol 2h 2 times, each 2h, merge extractive liquid,, filter, it is the extractum of 1.05 (50 ℃) that filtrate decompression concentrates (≤70 ℃) to relative density, the water that adds 4 times of amounts fully stirs, standing over night, filter, AB-8 macroporous adsorbent resin on the filtrate, use 2 times of bed volume water, 2 times of bed volume 25% ethanol, 2 times of bed 75% ethanol elutions respectively, collect 75% ethanol elution, reclaim ethanol concentrating under reduced pressure and 60 ℃ of vacuum drying extract II;
(3) injection water 600ml will be added after extract I and the extract II merging, heated and boiled 8 minutes, naturally put coldly, cold preservation 24h filters, it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collect ultrafiltrate 1000ml, the cold preservation after-filtration that spends the night adds mannitol and the 2gPVP of 100g in the filtrate, filter, filtrate is added water for injection to 1050ml, adjust pH 6.5～7.0,0.22 μ m microporous filter membrane aseptic filtration, filtrate is sub-packed in the 7ml cillin bottle, every bottle of 3.5ml jumps a queue, lyophilization, packing gets lyophilized injectable powder.
The preparation of embodiment 2 freeze dried Mailuoning powders
(1) gets the 2000g Flos Lonicerae powder and be broken into coarse powder, cross sieve No. 2, with 75% ethanol percolate extraction of 12 times of amounts, the 20h percolation finishes, and percolate filters, subsequent filtrate reclaims ethanol, being evaporated to relative density is the extractum of 1.15 (50 ℃), and centrifugal removal insoluble impurities adds 6 times of water gagings, fully stir, standing over night is filtered, and filtrate decompression is concentrated into the extractum that relative density is 1.20 (50 ℃), filter, remove precipitation, 30% hydrochloric acid is regulated pH value to 3, equal-volume ethyl acetate extraction 4 times, combining extraction liquid, 60 ℃ of vacuum dryings get extract I after the recovery ethyl acetate;
(2) get each 2000g of Radix Achyranthis Bidentatae, Herba Dendrobii, Radix Scrophulariae and pulverize the back with reflux, extract, behind the 70% soak with ethanol 3h 3 times, each 1h, merge extractive liquid,, filter, it is the extractum of 1.20 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), the water that adds 6 times of amounts fully stirs, standing over night, filter, AB-8 macroporous adsorbent resin on the filtrate, use 2 times of bed volume water, 2 times of bed volume 25% ethanol, 2 times of bed 75% ethanol elutions respectively, collect 75% ethanol elution, reclaim ethanol concentrating under reduced pressure and 60 ℃ of vacuum drying extract II;
(3) injection water 1200ml heated and boiled 10 minutes will be added after extract I and the extract II merging, naturally put cold, cold preservation 24h, filter, it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collects ultrafiltrate 1500ml, the cold preservation after-filtration that spends the night, add 100g mannitol and 3gPVP in the filtrate, filter, filtrate is added water for injection to 1575ml, adjust pH 6.5～7.0,0.22 the aseptic filtration of μ m microporous filter membrane, filtrate is sub-packed in the 7ml cillin bottle, every bottle of 3.5ml, jump a queue, lyophilization, packing gets lyophilized injectable powder.
The preparation of embodiment 3 freeze dried Mailuoning powders
(1) gets the 5000g Flos Lonicerae powder and be broken into coarse powder, cross sieve No. 2, with 90% ethanol percolate extraction of 14 times of amounts, the 30h percolation finishes, and percolate filters, subsequent filtrate reclaims ethanol, being evaporated to relative density is the extractum of 1.25 (50 ℃), and centrifugal removal insoluble impurities adds 5 times of water gagings, fully stir, standing over night is filtered, and filtrate decompression is concentrated into the extractum that relative density is 1.15 (50 ℃), filter, remove precipitation, 20% hydrochloric acid is regulated pH value to 4, equal-volume ethyl acetate extraction 5 times, combining extraction liquid, 60 ℃ of vacuum dryings get extract I after the recovery ethyl acetate;
(2) get each 4500g of Radix Achyranthis Bidentatae, Herba Dendrobii, Radix Scrophulariae and pulverize the back with reflux, extract, behind the 80% soak with ethanol 2h 2 times, each 3h, merge extractive liquid,, filter, it is the extractum of 1.05 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), the water that adds 5 times of amounts fully stirs, standing over night, filter, SA-1 macroporous adsorbent resin on the filtrate, use 2 times of bed volume water, 2 times of bed volume 25% ethanol, 2 times of bed 75% ethanol elutions respectively, collect 75% ethanol elution, reclaim ethanol concentrating under reduced pressure and 60 ℃ of vacuum drying extract II;
(3) injection water 2000ml heated and boiled 10 minutes will be added after extract I and the extract II merging, naturally put cold, cold preservation 24h, filter, it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collects ultrafiltrate 3000ml, the cold preservation after-filtration that spends the night, add 275g mannitol and 5gPVP in the filtrate, filter, filtrate is added water for injection to 3500, adjust pH 6.5～7.0,0.22 the aseptic filtration of μ m microporous filter membrane, filtrate is sub-packed in the 7ml cillin bottle, every bottle of 3.5ml, jump a queue, lyophilization, packing gets lyophilized injectable powder.
The preparation of embodiment 4 freeze dried Mailuoning powders
(1) gets the 4500g Flos Lonicerae powder and be broken into coarse powder, cross sieve No. 2, with 80% ethanol percolate extraction of 12 times of amounts, the 20h percolation finishes, percolate filters, subsequent filtrate reclaims ethanol, and concentrating under reduced pressure (temperature≤70 ℃) to relative density is the extractum of 1.20 (50 ℃), centrifugal removal insoluble impurities, add 6 times of water gagings, fully stir, standing over night is filtered, it is the extractum of 1.15 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), filter, remove precipitation, filtrate is determined volume, 20% hydrochloric acid is regulated pH value to 2, equal-volume ethyl acetate extraction 6 times, combining extraction liquid, 60 ℃ of vacuum dryings get extract I after the recovery ethyl acetate;
(2) get Radix Achyranthis Bidentatae, Herba Dendrobii, each 4500g of Radix Scrophulariae pulverizes the back with reflux, extract, behind the 70% soak with ethanol 1.5h 2 times, each 2h, add for the first time 8 times of amounts, add for the second time 6 times of amounts, merge extractive liquid,, filter, it is the extractum of 1.15 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), the water that adds 5 times of amounts fully stirs, and standing over night is filtered, AB-8 or SA-1 macroporous adsorbent resin on the filtrate, use 2 times of bed volume water rinse resins respectively, 2 times of bed volume 25% alcohol flushing impurity, 2 times of bed 75% ethanol elutions are collected 75% ethanol elution, reclaim ethanol concentrating under reduced pressure and 60 ℃ of vacuum drying extract II;
(3) injection water 2000ml will be added after extract I and the extract II merging, heated and boiled 10 minutes, naturally put coldly, cold preservation 24h filters, it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collect ultrafiltrate 3000ml, the cold preservation after-filtration that spends the night adds 265g mannitol and 5gPVP in the filtrate, filter, filtrate is added water for injection to 3500ml, adjust pH to 6.5～7.0,0.22 μ m microporous filter membrane aseptic filtrations, filtrate is sub-packed in the 7ml cillin bottle, every bottle of 3.5ml jumps a queue, lyophilization, packing gets lyophilized injectable powder.
The preparation of embodiment 5 freeze dried Mailuoning powders
(1) gets the 6000g Flos Lonicerae powder and be broken into coarse powder, cross sieve No. 2, with 80% ethanol percolate extraction of 12 times of amounts, the 20h percolation finishes, percolate filters, subsequent filtrate reclaims ethanol, and concentrating under reduced pressure (temperature≤70 ℃) to relative density is the extractum of 1.05 (50 ℃), centrifugal removal insoluble impurities, add 6 times of water gagings, fully stir, standing over night is filtered, it is the extractum of 1.05 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), filter, remove precipitation, filtrate is determined volume, 20% hydrochloric acid is regulated pH value to 2, equal-volume ethyl acetate extraction 6 times, combining extraction liquid, 60 ℃ of vacuum dryings get extract I after the recovery ethyl acetate;
(2) get Radix Achyranthis Bidentatae, Herba Dendrobii, each 6000g of Radix Scrophulariae pulverizes the back with reflux, extract, behind the 70% soak with ethanol 1.5h 2 times, each 2h, add for the first time 8 times of amounts, add for the second time 6 times of amounts, merge extractive liquid,, filter, it is the extractum of 1.15 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), the water that adds 6 times of amounts fully stirs, and standing over night is filtered, AB-8 macroporous adsorbent resin on the filtrate, use 2 times of bed volume water rinse resins respectively, 2 times of bed volume 25% alcohol flushing impurity, 2 times of bed 75% ethanol elutions are collected 75% ethanol elution, reclaim ethanol concentrating under reduced pressure and 60 ℃ of vacuum drying extract II;
(3) injection water 2500ml heated and boiled 10 minutes will be added after extract I and the extract II merging, naturally put cold, cold preservation 24h, filter, it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collects ultrafiltrate 3500ml, the cold preservation after-filtration that spends the night, add 350g mannitol and 6gPVP in the filtrate, filter, filtrate is added water for injection to 4550ml, adjust pH 6.5～7.0,0.22 the aseptic filtration of μ m microporous filter membrane, filtrate is sub-packed in the 7ml cillin bottle, every bottle of 3.5ml, jump a queue, lyophilization, packing gets lyophilized injectable powder.
The preparation of embodiment 6 freeze dried Mailuoning powders
(1) gets the 3000g Flos Lonicerae powder and be broken into coarse powder, cross sieve No. 2, with 80% ethanol percolate extraction of 10 times of amounts, the 25h percolation finishes, percolate filters, subsequent filtrate reclaims ethanol, and concentrating under reduced pressure (temperature≤70 ℃) to relative density is the extractum of 1.20 (50 ℃), centrifugal removal insoluble impurities, add 6 times of water gagings, fully stir, standing over night is filtered, it is the extractum of 1.20 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), filter, remove precipitation, filtrate is determined volume, 20% hydrochloric acid is regulated pH value to 2.5, equal-volume ethyl acetate extraction 6 times, combining extraction liquid, 60 ℃ of vacuum dryings get extract I after the recovery ethyl acetate;
(2) get Radix Achyranthis Bidentatae, Herba Dendrobii, each 3000g of Radix Scrophulariae pulverizes the back with reflux, extract, behind the 70% soak with ethanol 2h 2 times, each 2h, add for the first time 8 times of amounts, add for the second time 6 times of amounts, merge extractive liquid,, filter, it is the extractum of 1.15 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), the water that adds 5 times of amounts fully stirs, and standing over night is filtered, SA-1 macroporous adsorbent resin on the filtrate, use 2 times of bed volume water rinse resins respectively, 2 times of bed volume 25% alcohol flushing impurity, 2 times of bed 75% ethanol elutions are collected 75% ethanol elution, reclaim ethanol concentrating under reduced pressure and 60 ℃ of vacuum drying extract II;
(3) injection water 1500ml heated and boiled 10 minutes will be added after extract I and the extract II merging, naturally put cold, cold preservation 24h, filter, it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collects ultrafiltrate 2000ml, the cold preservation after-filtration that spends the night, add 180g mannitol and 2gPVP in the filtrate, filter, filtrate is added water for injection to 2500ml, adjust pH 6.5～7.0,0.22 the aseptic filtration of μ m microporous filter membrane, filtrate is sub-packed in the 7ml cillin bottle, every bottle of 3.5ml, jump a queue, lyophilization, packing gets lyophilized injectable powder.
The preparation of embodiment 7 MAILUONING ZHUSHEYE
(1) gets the 4500g Flos Lonicerae powder and be broken into coarse powder, cross sieve No. 2, with 75% ethanol percolate extraction of 10 times of amounts, the 20h percolation finishes, percolate filters, subsequent filtrate reclaims ethanol, and concentrating under reduced pressure (temperature≤70 ℃) to relative density is the extractum of 1.20 (50 ℃), centrifugal removal insoluble impurities, add 6 times of water gagings, fully stir, standing over night is filtered, it is the extractum of 1.20 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), filter, remove precipitation, filtrate is determined volume, 30% hydrochloric acid is regulated pH value to 2, equal-volume ethyl acetate extraction 6 times, combining extraction liquid, 60 ℃ of vacuum dryings get extract I after the recovery ethyl acetate;
(2) get Radix Achyranthis Bidentatae, Herba Dendrobii, each 5000g of Radix Scrophulariae pulverizes the back with reflux, extract, behind the 70% soak with ethanol 2h 2 times, each 2h, add for the first time 8 times of amounts, add for the second time 6 times of amounts, merge extractive liquid,, filter, it is the extractum of 1.15 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), the water that adds 4 times of amounts fully stirs, and standing over night is filtered, SA-1 macroporous adsorbent resin on the filtrate, use 2 times of bed volume water rinse resins respectively, 2 times of bed volume 25% alcohol flushing impurity, 2 times of bed 75% ethanol elutions are collected 75% ethanol elution, reclaim ethanol concentrating under reduced pressure and 60 ℃ of vacuum drying extract II;
(3) injection water 2500ml heated and boiled 10 minutes will be added after extract I and the extract II merging, naturally put cold, cold preservation 24h, filter, it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collects ultrafiltrate 3000ml, the cold preservation after-filtration that spends the night, add 270g mannitol and 5gPVP in the filtrate, filter, filtrate is added water for injection to 3500ml, adjust pH 6.5～7.0,0.22 μ m microporous filter membrane aseptic filtration, filtrate is sub-packed in the 7ml cillin bottle, every bottle of 3.5ml, sterilization rear seal-cover, packing gets injection.
The preparation of embodiment 8 MAILUONING ZHUSHEYE
(1) gets the 4500g Flos Lonicerae powder and be broken into coarse powder, cross sieve No. 2, with 80% ethanol percolate extraction of 12 times of amounts, the 20h percolation finishes, percolate filters, subsequent filtrate reclaims ethanol, and concentrating under reduced pressure (temperature≤70 ℃) to relative density is the extractum of 1.20 (50 ℃), centrifugal removal insoluble impurities, add 6 times of water gagings, fully stir, standing over night is filtered, it is the extractum of 1.15 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), filter, remove precipitation, filtrate is determined volume, 20% hydrochloric acid is regulated pH value to 2, equal-volume ethyl acetate extraction 6 times, combining extraction liquid, 60 ℃ of vacuum dryings get extract I after the recovery ethyl acetate;
(2) get Radix Achyranthis Bidentatae, Herba Dendrobii, each 4500g of Radix Scrophulariae pulverizes the back with reflux, extract, behind the 70% soak with ethanol 1.5h 2 times, each 2h, add for the first time 8 times of amounts, add for the second time 6 times of amounts, merge extractive liquid,, filter, it is the extractum of 1.15 (50 ℃) to relative density that filtrate decompression concentrates (temperature≤70 ℃), the water that adds 5 times of amounts fully stirs, and standing over night is filtered, AB-8 or SA-1 macroporous adsorbent resin on the filtrate, use 2 times of bed volume water rinse resins respectively, 2 times of bed volume 25% alcohol flushing impurity, 2 times of bed 75% ethanol elutions are collected 75% ethanol elution, reclaim ethanol concentrating under reduced pressure and 60 ℃ of vacuum drying extract II;
(3) injection water 2000ml will be added after extract I and the extract II merging, heated and boiled 10 minutes, naturally put cold, cold preservation 24h filters, and it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collect ultrafiltrate 3000ml, the cold preservation after-filtration that spends the night adds 265g mannitol and 5gPVP in the filtrate, filter, filtrate is added water for injection to 3500ml, adjust pH to 6.5～7.0,0.22 μ m microporous filter membrane aseptic filtrations, filtrate is sub-packed in the 7ml cillin bottle, every bottle of 3.5ml, the sterilization rear seal-cover, packing gets injection.
Claims (3)
1. the preparation method of a 'Mailuoning ' injection preparation is characterized in that, may further comprise the steps:
(1) extracting honeysuckle is ground into coarse powder, cross sieve No. 2, with 50～95% ethanol percolate extraction of 8～16 times of amounts, 10～40h percolation finishes, and percolate filters, subsequent filtrate reclaims ethanol, 50 ℃ are evaporated to relative density is 1.05～1.30 extractum, and centrifugal removal insoluble impurities adds 4～8 times of water gagings, fully stir, standing over night is filtered, and it is 1.05～1.25 extractum that 50 ℃ of filtrates are evaporated to relative density, filter, remove precipitation, 10%～30% hydrochloric acid is regulated pH value to 2～6, ethyl acetate extraction 2～6 times, combining extraction liquid, 60 ℃ of vacuum dryings get the extract I after the recovery ethyl acetate;
(2) get Radix Achyranthis Bidentatae, Herba Dendrobii, Radix Scrophulariae and pulverize the back with reflux, extract, behind 50%～90% soak with ethanol, 1～3h 2～3 times, each 1～3h, merge extractive liquid,, filter, it is 1.05～1.20 extractum that 50 ℃ of filtrates are evaporated to relative density, the water that adds 4～6 times of amounts fully stirs, standing over night, filter, Semi-polarity or strong polar macroporous adsorption resin on the filtrate, use 2 times of bed volume water, 2 times of bed volume 25% ethanol, 2 times of bed 75% ethanol elutions respectively, collect 75% ethanol elution, reclaim ethanol concentrating under reduced pressure and 60 ℃ of vacuum drying extract II;
(3) will the extract I and the extract II add injection water heated and boiled 8～15 minutes after merging, put naturally cold, cold preservation 24h, filter, it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collects ultrafiltrate, the cold preservation after-filtration that spends the night adds the mannitol and the PVP of recipe quantity in the filtrate, filter, filtrate is added water for injection to recipe quantity, adjust pH 6.5～7.0, aseptic filtration, filtrate is sub-packed in the cillin bottle, jumps a queue lyophilization, packing gets lyophilized injectable powder; Or the sterilization rear seal-cover, packing gets injection;
Described Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii and Chinese medicine honeysuckle were according to 1: 1: 1: 1 weight portion proportioning.
2. the preparation method of 'Mailuoning ' injection preparation as claimed in claim 1 is characterized in that, may further comprise the steps:
(1) extracting honeysuckle is ground into coarse powder, cross sieve No. 2, with 80% ethanol percolate extraction of 12 times of amounts, the 20h percolation finishes, percolate filters, subsequent filtrate reclaims ethanol, and it is 1.20 extractum that temperature≤70 ℃ are evaporated to 50 ℃ of relative densities, centrifugal removal insoluble impurities, add 6 times of water gagings, fully stir, standing over night is filtered, it is 1.15 extractum that filtrate temperature≤70 ℃ are evaporated to 50 ℃ of relative densities, filter, remove precipitation, filtrate is determined volume, 20% hydrochloric acid is regulated pH value to 2, equal-volume ethyl acetate extraction 6 times, combining extraction liquid, 60 ℃ of vacuum dryings get the extract I after the recovery ethyl acetate;
(2) get Radix Achyranthis Bidentatae, Herba Dendrobii, Radix Scrophulariae is pulverized the back with reflux, extract, behind the 70% soak with ethanol 1.5h 2 times, each 2h, add for the first time 8 times of amounts, add for the second time 6 times of amounts, merge extractive liquid,, filter, it is 1.15 extractum that filtrate temperature≤70 ℃ are evaporated to 50 ℃ of relative densities, the water that adds 5 times of amounts fully stirs, and standing over night is filtered, AB-8 or SA-1 macroporous adsorbent resin on the filtrate, use 2 times of bed volume water rinse resins respectively, 2 times of bed volume 25% alcohol flushing impurity, 2 times of bed 75% ethanol elutions are collected 75% ethanol elution, reclaim ethanol concentrating under reduced pressure and 60 ℃ of vacuum drying extract II;
(3) will the extract I and the extract II add injection water heated and boiled 10 minutes after merging, put naturally cold, cold preservation 24h, filter, it is 3000 ultrafilter membrane ultrafiltration that filtrate is crossed molecular cut off, collects ultrafiltrate, the cold preservation after-filtration that spends the night adds the mannitol and the PVP of recipe quantity in the filtrate, filter, filtrate is added water for injection to recipe quantity, adjust pH 6.5～7.0, aseptic filtration, filtrate is sub-packed in the cillin bottle, jumps a queue lyophilization, packing gets lyophilized injectable powder; Or the sterilization rear seal-cover, packing gets injection.
3. the preparation method of 'Mailuoning ' injection preparation as claimed in claim 2 is characterized in that, the macroporous adsorbent resin described in the step (2) is a SA-1 type macroporous adsorbent resin.
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| CN1557347A (en) * | 2004-01-13 | 2004-12-29 | 吴良信 | Medicine for treating cardiac and cerebral vascular diseases and its preparation |
| CN1562093A (en) * | 2004-03-19 | 2005-01-12 | 秦吉兴 | Method for preparing mailuoning freeze-dried powder for injection |
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| CN1557347A (en) * | 2004-01-13 | 2004-12-29 | 吴良信 | Medicine for treating cardiac and cerebral vascular diseases and its preparation |
| CN1562093A (en) * | 2004-03-19 | 2005-01-12 | 秦吉兴 | Method for preparing mailuoning freeze-dried powder for injection |
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