CN1899369A - Heart resurrecting injection preparation and its preparing method - Google Patents
Heart resurrecting injection preparation and its preparing method Download PDFInfo
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- CN1899369A CN1899369A CNA2005100870180A CN200510087018A CN1899369A CN 1899369 A CN1899369 A CN 1899369A CN A2005100870180 A CNA2005100870180 A CN A2005100870180A CN 200510087018 A CN200510087018 A CN 200510087018A CN 1899369 A CN1899369 A CN 1899369A
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Abstract
The present invention discloses a kind of heart resurrecting injection preparation and its preparation process, and features that the heart resurrecting injection preparation has improved recipe of traditional Chinese medicine Liushen preparation. The heart resurrecting injection preparation is prepared with the extracts of Chinese medicine materials bezoar, musk, ginseng and red sage and medicinal supplementary material, and may be prepared into injection, transfused fluid or powder for injection. Pharmaceutical research and experiment proves its high curative effect on cardiac vascular diseases and very good pharmaceutical function.
Description
Affiliated technical field
The invention belongs to technical field of traditional Chinese medicine pharmacy, be specifically related to a kind of heart resurrecting injection preparation and preparation method thereof.
Background technology
The watered pill that LIUSHEN WAN is made up of Moschus, Calculus Bovis, Borneolum Syntheticum, Margarita, Realgar and Venenum Bufonis has functions such as detoxifcation, detumescence, pain relieving; LIUSHEN WAN was the key medicine of clinical treatment pharyngeal heat and detoxicating originally, and through the later age of practice and exploring constantly, curative effects such as LIUSHEN WAN treatment cardiovascular disease are proved; The Japan's prescription and genuine Chinese medicine raw material of China's " LIUSHEN WAN ", become famous JIUXIN DAN after transforming a little and packing, the national medicine of robbing China with the method for changing to a new form is cultural and economical, begin by the LIUSHEN WAN prescription, the pills for curing heart disease that centers on this basic side later on and occur, Japan's JIUXIN DAN, YIXIN WAN, coronary heart disease pill, heart pellet alive, Heart pill of Musk etc. all are the new sides who formulates in view of the above, the location that cures mainly because of these new side's functions is mainly aspect the cardiovascular, all used the titles such as " rescuing the heart " that to express its effect simultaneously, along with deepening continuously of LIUSHEN WAN clinical research, prior dosage form can not satisfy the needs of clinical practice, develops rapid onset, the novel form that meets the clinical application needs is imperative.
The LIUSHEN WAN modern pharmacological research shows, the Main Ingredients and Appearance and the mechanism of action of this side's treatment cardiovascular disease are clear and definite substantially, remove the heavy metal composition that easily causes untoward reaction among the former side of LIUSHEN WAN if change sanction, the core active ingredient that keeps the former side's monarch of performance, the very suitable novel form that meets modern medication that is developed as.
Coronary heart disease is meant that coronary atherosclerosis causes myocardial ischemia, anoxia and the heart disease that causes, and wherein angina pectoris belongs to the category of Chinese medicine " precordial pain with cold limbs ", " angina pectoris ", " thoracic obstruction ", is old people's commonly encountered diseases, frequently-occurring disease.Its performance mainly is a stuffy pain over the chest, and very then chest pain radiating to the back is breathed hard and panted, must not peacefully sleeping etc. disease.Clinical often by flaccidity of the heart-yang due to inward invasion of pathogenic cold, eating and drinking without temperance, incoordination of seven emotions, the factor such as old, blockage of the cardiac vessels, QI and blood is popular not smooth, qi depression to blood stasis, finally cause the heart lose blood foster, the blood vessels operation is smooth and bring out angina pectoris.Between the clinical common qi depression to blood stasis of above reason, the turbid obstruction of expectorant, YIN-cold stagnate, deficiency of both QI and YIN, five pattern of syndrome of deficient and weak YANG QI.Work as qi depression to blood stasis, functional activity of QI being not smooth in the heart, then occur uncomfortable in chest, breathe hard; Heart arteries and veins is obstructed, stagnation of QI and blood may bring about pain, then ambition pain; Blood stasis stagnates, and then sore spot is fixing does not move; In a word, the thoracic obstruction finally is that its sick position is mainly at the heart, and is relevant with liver,spleen,kidney, belongs to the card of deficiency in origin and excess in superficiality owing to lose blood foster, qi and blood stagnation of the heart brings out.Mark is real blood stasis, YIN-cold, difference that expectorant is turbid, and deficiency in origin has the difference of negative and positive of qi and blood again.Then work as with promoting flow of QI and blood for coronary heart disease, angina pectoris due to the qi and blood stagnation, stasis-dispelling and pain-killing is a method.
Summary of the invention
For these reasons; we are theoretical and modern science and technology means according to modern Chinese medicine; to tradition six refreshing prescription sanctions; obtain the new heart prescription of rescuing: with Calculus Bovis, Moschus compatibility Radix Ginseng, Radix Salviae Miltiorrhizae; be prepared into heart resurrecting injection preparation; The pharmacological results shows that the present invention respectively organizes preparation and has better pharmacological action.
Calculus Bovis is cool in nature in the heart resurrecting injection preparation side, and bitter in the mouth is flat, the have one's ideas straightened out effect of refreshment, eliminating phlegm arresting convulsion of tool, to phlegm-turbidity and blood stasis hinder, the angina pectoris of caused by energy stagnation and blood stasis has the effect of symptomatic treatment, with being monarch drug; Radix Salviae Miltiorrhizae in the side, Moschus are warm in nature, and the effect of tool promoting flow of QI and blood, acupuncture-stimulating blood stasis dispersing pain relieving is with being ministerial drug; Radix Ginseng strongly invigorating primordial QI, tonification the five internal organs in the side have the effect of auxiliary treatment to the angina pectoris due to malnutrition of heart blood, the qi and blood stagnation, with being adjuvant drug.All medicines are associated with, and play promoting flow of QI and blood altogether, stasis-dispelling and pain-killing, and the merit of analepsia emergency is effectively alleviated the angina pectoris due to the qi and blood stagnation.
What the object of the present invention is to provide a kind of new, better efficacy rescues heart prescription.
The present invention also aims to provide a kind of preparation method of heart resurrecting injection preparation.
The present invention is achieved through the following technical solutions.
One. process recipes
(1) raw material medicines in portions by weight of the present invention:
Calculus Bovis 6-15, Moschus 5-15, Radix Ginseng 120-180, Radix Salviae Miltiorrhizae 100200;
(2) get Moschus, extracted 4-8 hour, obtain Moschus extract, filter standby with 2-6 times of 95% ethanol continuous backflow;
(3) get Calculus Bovis, adding 3-6 times of water gaging decocts 2 times, merge decocting liquid, filter, supernatant adds 0.5% activated carbon decolorizing, solution concentrate under reduced pressure at low temperature to 50 ℃ relative density after the decolouring is the extractum of 1.05-1.10, adds ethanol again and makes and contain alcohol amount and reach 70%, leaves standstill 24 hours, filter, supernatant decompression recycling ethanol, and concentrate 50 ℃ of extractum that relative density is 1.05-1.10 adds ethanol and makes and contain the alcohol amount and reach 80%, leave standstill cold preservation more than 24 hours, filter, the supernatant decompression recycling ethanol also concentrates, and cold drying obtains Calculus Bovis extract;
(4) Radix Salviae Miltiorrhizae is pulverized, and is that aqueous alkali more than 10 is carried 2-3 time with pH, and temperature is 80-100 ℃, each 60-120 minute, merge extractive liquid,, centrifugal, get supernatant, being evaporated to 50 ℃ of relative densities is 1.10-1.15, transfers pH6.5-7, adding ethanol makes and contains the alcohol amount and reach 70%-80%, leave standstill, filter, filtrate recycling ethanol is to most, being evaporated to 50 ℃ of relative densities is 1.20-1.30, add ethanol again and make and contain alcohol amount 75%-85%, leave standstill, in solution, by volume add 1% active carbon, stirred 1 hour, filter, filter, filtrate recycling ethanol is to most, the concentrating under reduced pressure drying obtains Radix Salviae Miltiorrhizae extract;
(5) get the Radix Ginseng powder and be broken into coarse powder, add the alcohol reflux 2 times that 5-8 doubly measures 60%-80%, extracting solution filters, add water to every milliliter behind the recovery ethanol and contain the 0.8-1g crude drug, cold preservation 24 hours, centrifugal, D101 macroporous resin adsorption on the supernatant, the washing of doubly measuring earlier with 2-3, reuse 70%-90% ethanol elution is collected the 70%-90% ethanol elution, decompression recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.10 extractum, adding ethanol makes and contains alcohol amount and reach more than 80%, cold preservation 24 hours filters, filtrate recycling ethanol, spray drying gets Radix Ginseng extract;
(6) prescription of preparation:
Aqueous injection: Calculus Bovis extract 2.0-5.0 weight portion, Moschus extract 0.5-2.0 weight portion, Radix Ginseng extract 6.0-15.0 weight portion, Radix Salviae Miltiorrhizae 4.0-10.0 weight portion;
Infusion solution: Calculus Bovis extract 2.0-5.0 weight portion, Moschus extract 0.5-2.0 weight portion, Radix Ginseng extract 6.0-15.0 weight portion, Radix Salviae Miltiorrhizae 4.0-10.0 weight portion;
Injectable powder: Calculus Bovis extract 2.0-5.0 weight portion, Moschus extract 0.5-2.0 weight portion, Radix Ginseng extract 6.0-15.0 weight portion, Radix Salviae Miltiorrhizae 4.0-10.0 weight portion;
(7) formulation preparation:
The preparation of aqueous injection: get HP-β-CD that 20-30 doubly measures Moschus extract, add the solution that the injection water is made into 35-40%, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 20-30 minute, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 0-4 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.2-7.5, add 0.2% active carbon 50-60 ℃ of insulation 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, sterilize, stop leakage in the roof, be packaged to be aqueous injection;
The preparation of infusion solution: get HP-β-CD that 20-30 doubly measures Moschus extract, add the solution that the injection water is made into 35-40%, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 20-30 minute, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 0-4 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.2-7.5, add 0.2% active carbon 50-60 ℃ of insulation 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, 115 ℃ of pressure sterilizings, lamp inspection, be packaged to be infusion solution;
The preparation of injectable powder: get HP-β-CD that 20-30 doubly measures Moschus extract, add the solution that the injection water is made into 35-40%, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 20-30 minute, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 0-4 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed; add freeze-dried excipient; transfer pH value to 6.8-7.5 with 20% sodium hydroxide; supply volume with water for injection; add 0.2% active carbon 50-60 ℃ of insulation 30 minutes; take off charcoal, fine straining, fill, half tamponade, lyophilization, gland, test package obtains injectable powder.
Two. check and analysis
1. the test experience of muscone
Muscone is the main effective ingredient of Moschus, and the present invention adopts gas chromatography that the present invention is respectively organized preparation and analyzes comparison.
Instrument: HP-5890A gas chromatograph, electronic balance, volatile oil determination apparatus.
Experiment medicine: muscone reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute's purchase); Heart resurrecting injection preparation of the present invention (Tianzhijiao Medication Development Co., Ltd., Guangdong); (analytical pure, the Beijing Chemical Plant buys benzene.)
Chromatographic condition: chromatographic column: the stainless steel column of HP-10%OV-17CHROMOSORB WHP 2m*2mm (ID), 220 ℃ of column temperatures, 270 ℃ of temperature of vaporization chamber, 260 ℃ of sensing chamber's temperature, nitrogen is carrier gas, pressure 200kpa, detector FID, sensitivity 2; Sample size 1ul.
Formulations prepared from solutions:
Reference substance preparation: get muscone 10mg, the accurate title in the 10ml volumetric flask, is with the benzene dissolving and be diluted to scale, mixing.
Need testing solution: get the present invention and respectively organize preparation and put into the determination of volatile oil device, add water 230ml, add benzene 1ml, slowly heating, little boiling 3 hours left standstill 1 hour, took out benzene gold-plating liquid and moved in the 2ml volumetric flask, was diluted to scale with benzene, made need testing solution.
Sample determination: get reference substance, sample carries out gas chromatographic analysis, carry out linear experiment of reference substance and precision experiment, calculate the content of respectively organizing the muscone in the preparation, see Table 1 with external standard method:
2. bilirubinic check and analysis
Bilirubin is one of main effective ingredient of Calculus Bovis, and the present invention adopts high performance liquid chromatography that preparation is carried out check and analysis.
Experimental apparatus: day island proper Tianjin LC-6A high performance liquid chromatograph.
The experiment medicine: chloroform, glacial acetic acid (analytical pure), methanol (analytical pure), acetonitrile (chromatographically pure) Beijing Chemical Plant buy; Bilirubin reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute's purchase); Heart resurrecting injection preparation of the present invention (Tianzhijiao Medication Development Co., Ltd., Guangdong)
Experimental technique:
Chromatographic condition: chromatographic column: ODS; Column temperature: 38 ℃; Detect wavelength: 450nm;
Accurately take by weighing bilirubin reference substance 10mg, put in the 50ml volumetric flask, add chloroform-1% methanol hydrochloride solution (5: 1) 40ml, supersound process 10 minutes is dissolved and is diluted to scale, shakes up, draw 1,3,5,7,9 microlitres successively, last sample, the drawing standard curve is: Y=9838.7X-2765.1, r=0.9997.
Precision takes by weighing (aqueous injection of the present invention, infusion solution are carried out drying) the present invention and respectively organizes preparation 20mg, put in the 50ml volumetric flask, add chloroform-1% methanol hydrochloride solution (5: 1) 40ml, supersound process 10 minutes, dissolving also is diluted to scale, shakes up last sample, obtain data and calculate, experimental result sees Table 1:
Table 1 the present invention respectively organizes the preparation active constituent content
| Group | Muscone content mg/ props up | Content of bilirubin mg/ props up |
| Aqueous injection of the present invention infusion solution of the present invention injectable powder of the present invention | 3.29 3.18 3.31 | 27.18 27.55 27.40 |
Conclusion: show that by above check and analysis experiment technology of the present invention has practical significance.
Three. toxicological experiment
Experiment 1
Studies on acute toxicity
The experiment medicine: the present invention respectively organizes heart resurrecting injection preparation (Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory provides);
Laboratory animal: healthy mice 18-22g,, male and female half and half.
Experimental technique: get mice, be divided into and rescue edema with the heart involved injection group, infusion solution group, injectable powder group, intraperitoneal administration or tail intravenously administrable, be converted into the mice dosage according to body surface area, administration every day 3 times continuous 7 days, is observed the dead mouse situation, record data are by the LD of improvement karber's method calculating sodium cantharidin injection preparation
50Value.
Experimental result: mouse tail vein gives heart resurrecting injection preparation, records the LD of this product
50Be 26.45g crude drug/kg (95% credible 24.28-28.75g crude drug/kg); This product is by the LD of intraperitoneal administration
50Be 35.47g crude drug/kg (95% credible 33.71-37.64g crude drug/kg).
Experiment 2
Long term toxicity research
Rats by intraperitoneal injection heart resurrecting injection preparation, administration detect each index after 90 days and after drug withdrawal recovered for 2 weeks: 1. general situation 2. hematological indices 3. blood parameters 4. dissect and pathological examination.The result shows that this product do not have influence to each index, the clinical practice dosage safety.
Beagle dog intravenous drip heart resurrecting injection preparation, administration detect each index after 90 days and after drug withdrawal recovered for 2 weeks: 1. general situation 2. hematological indices 3. blood parameters 4. intravital bone marrow check that 6. 5. Electrocardioscopy dissect and pathological examination.The result shows that this product do not have influence to each index, the clinical practice dosage safety.
Experiment 3
Safety research
Heart resurrecting injection preparation does not have haemolysis and red cell agglutination; The intravenous drip of rabbit ear edge, the medicine-feeding part blood vessel is not seen irritant reaction; The injection of rabbit quadriceps femoris does not see that injection site muscular tissue has irritant reaction; Systemic anaphylaxis does not appear in the Cavia porcellus administration; Rat there is not passive cutaneous anaphylaxis, PCA; The pyrogen reaction test is negative.
Experiment conclusion: show that by above experiment heart resurrecting injection preparation of the present invention has good safety.
Four. pharmacological evaluation
Anti-acute myocardial ischemia effect
Experiment medicine: heart resurrecting injection preparation of the present invention (Tianzhijiao Medication Development Co., Ltd., Guangdong's laboratory provides); Commercially available XIANGDAN ZHUSHEYE (Jiangsu Kang Yi pharmaceutical Co. Ltd product); LIUSHEN WAN (Shanghai Leiyun Pharmaceutical Industry Co., Ltd.).
Laboratory animal: hybrid dog, body weight 11.0-14.0kg.
Laboratory animal: get healthy hybrid dog, male and female all have, be divided into sham operated rats, model group (normal saline) at random, rescue edema with the heart involved injection group, infusion solution group, injectable powder group and XIANGDAN ZHUSHEYE group, LIUSHEN WAN group, rescuing heart preparation group dosage is 0.36g/kg, XIANGDAN ZHUSHEYE group dosage is 0.39ml/kg, LIUSHEN WAN group gastric infusion, and dosage is 0.80g/kg, 3% pentobarbital sodium (30mg/kg) intravenous injection row general anesthesia, back of the body position is fixing.Standby from right jugular vein intubate as blood drawing.Tracheostomize inserts tracheal casing pipe, connect the capable malleation artificial respiration of animal respirator (16 times/min).Right arm reclining is fixed, and opens breast in left IV intercostal, cuts off pericardium, exposes left anterior descending coronary artery (LAD) threading standby (doing ligation), puts 9 electrodes and make thought-read adventitia electrograph and use on the pericardium of appropriate location down.Surgical injury finishes, treat that all observation indexs are stable after, record normal index and blood drawing.Ligation arteria coronaria left anterior descending branch (LAD) duplicates myocardial infarction and ischemia model, stablizes 30min record index, then respectively by each group dosage intravenous drip administration (dripping off in the control 15min).The epicardial electrogram of each some when 30min, 60min, 120min after 30min and the administration before drawing blood respectively and writing down the ligation arteria coronaria, behind the ligation arteria coronaria.In the experimentation, the variation that continuous monitoring electrocardiogram II leads.Trace epicardial electrogram and electrocardiogram with collection of BL-410 bio signal and analytical equipment.
Observation index
(1) to the influence of myocardial ischemia scope: 1. trace epicardial electrogram at each time point with BL-410 bio signal system respectively, electrocardiogram ischemia scope (N-ST) is raised the summation of counting that exceeds 2mv with ST section in whenever leading and is represented.Degree of myocardial ischemia (∑-ST) represent with the summation of rising of ST section or fall in whenever leading.2. to the mensuration of myocardial infarct size: behind 180min, take off heart and carry out the NBT of cardiac muscular tissue dyeing, measure the scope (infarcted region/left chamber heavy * 100%) of infarction with weight method.
(2) sero-enzyme is measured: respectively at getting blood during 180min before pricking and after the administration, separation of serum is used automatic biochemical analyzer and is measured serum lactate dehydrogenase (SLD) (LDH) and creatine phosphokinase (CPK).
Experimental result
Influence to epicardial electrogram N-ST and ∑-ST
Table 1 rescue heart preparation to myocardial ischemia dog epicardial electrogram influence (x ± s, n=6)
| Detection time | Group | Prick back 30min | 30min begins administration after the ligation | ||
| 30min after the administration | 60min after the administration | 120min after the administration | |||
| N-ST ∑-ST | The fragrant red group Liushen Pills group of the fragrant red group Liushen Pills group sham-operation model group liquid drugs injection group transfusion group powder pin group of sham-operation model group liquid drugs injection group transfusion group powder pin group | 0.20±0.45 ** 8.40±0.89 8.37±0.46 8.41±0.45 8.48±0.53 8.40±0.55 8.37±0.44 8.28±2.66 ** 29.84±11.24 41.79±6.12 41.16±6.82 41.62±5.54 38.18±2.11 37.51±3.31 | 0.20±0.45 ** 8.20±1.30 5.78±1.33 * 5.64±1.27 * 5.60±1.34 * 6.00±1.22 * 6.31±1.37 * 8.80±1.73 ** 28.13±10.45 21.10±5.14 △△ 21.78±3.76 △△ 20.00±2.40 △△ 19.16±1.23 △ 24.32±1.54 | 0.00±0.00 ** 8.40±0.80 5.78±0.39 ** 5.82±0.43 ** 5.80±0.40 ** 6.20±1.47 * 6.54±1.59 * 8.33±1.28 ** 28.14±9.23 18.05±1.72 △△ 18.00±1.95 △△ 18.29±1.88 △△ 18.94±0.76 △ 23.47±1.03 △ | 0.00±0.00 ** 8.20±0.98 5.20±1.63 5.23±1.58 * 5.20±1.60 * 6.20±1.40 ** 6.82±1.57 * 9.02±0.88 ** 25.78±7.84 20.83±0.47 △△ 20.40±0.53 △△ 20.09±0.60 △△ 19.49±0.94 △ 22.58±0.75 △ |
Annotate: compare with model group,
*P＜0.05,
*P＜0.01; With contrast before the administration,
△P＜0.05,
△ △The influence of P＜0.01 pair myocardial infarct size
The influence of table 2 pair myocardial ischemia dog myocardial infarction scope (x ± s, n=6)
| Group | Myocardial infarct size (%) |
| Sham-operation group model control group liquid drugs injection group transfusion group powder pin group Clary injection group Liushen Pills group | 0.99±0.88 ** 14.80±3.54 6.51±2.00 ** 6.58±1.86 ** 6.48±2.68 ** 8.05±3.37 * 9.57±3.81 * |
Annotate: compare with model group,
*P＜0.05,
*P＜0.01; To sero-enzyme (LDH, CK) influence of level
Table 3 rescue heart preparation to the influence of myocardial ischemia dog LDH and CK (x ± s, n=6)
| Detection time | Group | Before the ligation | 180 min after the administration |
| LDH (U/L) CK (U/L) | Sham-operation group model control group liquid drugs injection group transfusion group powder pin group Clary injection group Liushen Pills group sham-operation group model control group liquid drugs injection group transfusion group powder pin group Clary injection group Liushen Pills group | 176±51 228±47 172±48 175±47 179±46 185±38 189±39 245±62 430±90 358±137 362±140 360±132 338±76 327±72 | 212±44 ** 561±109 323±31 ** 327±33 ** 325±28 ** 371±59 ** 401±62 * 1231±437 3613±599 1744±659 ** 1754±659 ** 1758±694 ** 2220±642 * 2876±743 * |
Annotate: compare with model group,
*P＜0.05,
*P＜0.01;
Conclusion: show that by pharmacological evaluation heart resurrecting injection preparation of the present invention has better pharmacological action.
Five. preparation embodiment
Embodiment 1
(1) raw material medicines in portions by weight of the present invention:
Calculus Bovis 6 grams, Moschus 5 grams, Radix Ginseng 120 grams, Radix Salviae Miltiorrhizae 100 grams;
(2) get Moschus, extracted 4 hours, obtain Moschus extract, filter standby with 2 times of 95% ethanol continuous backflow;
(3) get Calculus Bovis, adding 3 times of water gagings decocts 2 times, merge decocting liquid, filter, supernatant adds 0.5% activated carbon decolorizing, solution concentrate under reduced pressure at low temperature to 50 ℃ relative density after the decolouring is 1.05 extractum, adds ethanol again and makes and contain alcohol amount and reach 70%, leaves standstill 24 hours, filter, supernatant decompression recycling ethanol, and to concentrate 50 ℃ of relative densities be 1.05 extractum adds ethanol and makes and contain the alcohol amount and reach 80%, leave standstill cold preservation more than 24 hours, filter, the supernatant decompression recycling ethanol also concentrates, and cold drying obtains Calculus Bovis extract;
(4) Radix Salviae Miltiorrhizae is pulverized, and is that aqueous alkali more than 10 is carried 2 times with pH, and temperature is 80 ℃, each 60 minutes, merge extractive liquid,, centrifugal, get supernatant, being evaporated to 50 ℃ of relative densities is 1.10, transfers pH6.5, adding ethanol makes and contains the alcohol amount and reach 70%, leave standstill, filter, filtrate recycling ethanol is to most, being evaporated to 50 ℃ of relative densities is 1.20, add ethanol again and make the alcohol amount of containing 75%, leave standstill, in solution, by volume add 1% active carbon, stirred 1 hour, filter, filter, filtrate recycling ethanol is to most, the concentrating under reduced pressure drying obtains Radix Salviae Miltiorrhizae extract;
(5) get the Radix Ginseng powder and be broken into coarse powder, add 5 times of amount alcohol reflux of 60% 2 times, extracting solution filters, add water to every milliliter behind the recovery ethanol and contain the 0.8g crude drug, cold preservation 24 hours, centrifugal, D101 macroporous resin adsorption on the supernatant, first washing with 2 times of amounts, reuse 70% ethanol elution is collected 70% ethanol elution, decompression recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.10 extractum, adding ethanol makes and contains alcohol amount and reach more than 80%, cold preservation 24 hours filters, filtrate recycling ethanol, spray drying gets Radix Ginseng extract;
(6) prescription of preparation:
Aqueous injection: Calculus Bovis extract 2.0 grams, Moschus extract 0.5 gram, Radix Ginseng extract 6.0 grams, Radix Salviae Miltiorrhizae 4.0 grams;
Infusion solution: Calculus Bovis extract 2.0 grams, Moschus extract 0.5 gram, Radix Ginseng extract 6.0 grams, Radix Salviae Miltiorrhizae 4.0 grams;
Injectable powder: Calculus Bovis extract 2.0 grams, Moschus extract 0.5 gram, Radix Ginseng extract 6.0 grams, Radix Salviae Miltiorrhizae 4.0 grams;
(7) formulation preparation:
The preparation of aqueous injection: the HP-β-CD that gets 20 times of amount Moschus extracts, add the injection water and be made into 35% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 20 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 0 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.2, add 50 ℃ of insulations of 0.2% active carbon 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, sterilize, stop leakage in the roof, be packaged to be 1000 bottles of aqueous injection;
The preparation of infusion solution: the HP-β-CD that gets 20 times of amount Moschus extracts, add the injection water and be made into 35% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 20 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 0 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.2, add 50 ℃ of insulations of 0.2% active carbon 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, 115 ℃ of pressure sterilizings, lamp inspection, be packaged to be 1000 bottles of infusion solutions;
The preparation of injectable powder: the HP-β-CD that gets 20 times of amount Moschus extracts, add the injection water and be made into 35% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 20 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 0 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed; add freeze-dried excipient; transfer pH value to 6.8 with 20% sodium hydroxide; supply volume with water for injection; add 0.2% active carbon 50-60 ℃ of insulation 30 minutes; take off charcoal, fine straining, fill, half tamponade, lyophilization, gland, test package obtains 1000 bottles of injectable powder.
Embodiment 2
(1) raw material medicines in portions by weight of the present invention:
Calculus Bovis 15 grams, Moschus 15 grams, Radix Ginseng 180 grams, Radix Salviae Miltiorrhizae 200 grams;
(2) get Moschus, extracted 8 hours, obtain Moschus extract, filter standby with 6 times of 95% ethanol continuous backflow;
(3) get Calculus Bovis, adding 6 times of water gagings decocts 2 times, merge decocting liquid, filter, supernatant adds 0.5% activated carbon decolorizing, solution concentrate under reduced pressure at low temperature to 50 ℃ relative density after the decolouring is 1.10 extractum, adds ethanol again and makes and contain alcohol amount and reach 70%, leaves standstill 24 hours, filter, supernatant decompression recycling ethanol, and to concentrate 50 ℃ of relative densities be 1.10 extractum adds ethanol and makes and contain the alcohol amount and reach 80%, leave standstill cold preservation more than 24 hours, filter, the supernatant decompression recycling ethanol also concentrates, and cold drying obtains Calculus Bovis extract;
(4) Radix Salviae Miltiorrhizae is pulverized, and is that aqueous alkali more than 10 is carried 3 times with pH, and temperature is 100 ℃, each 120 minutes, merge extractive liquid,, centrifugal, get supernatant, being evaporated to 50 ℃ of relative densities is 1.15, transfers pH7, adding ethanol makes and contains the alcohol amount and reach 80%, leave standstill, filter, filtrate recycling ethanol is to most, being evaporated to 50 ℃ of relative densities is 1.30, add ethanol again and make the alcohol amount of containing 85%, leave standstill, in solution, by volume add 1% active carbon, stirred 1 hour, filter, filter, filtrate recycling ethanol is to most, the concentrating under reduced pressure drying obtains Radix Salviae Miltiorrhizae extract;
(5) get the Radix Ginseng powder and be broken into coarse powder, add 8 times of amount alcohol reflux of 80% 2 times, extracting solution filters, add water to every milliliter behind the recovery ethanol and contain the 1g crude drug, cold preservation 24 hours, centrifugal, D101 macroporous resin adsorption on the supernatant, first washing with 3 times of amounts, reuse 90% ethanol elution is collected 90% ethanol elution, decompression recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.10 extractum, adding ethanol makes and contains alcohol amount and reach more than 80%, cold preservation 24 hours filters, filtrate recycling ethanol, spray drying gets Radix Ginseng extract;
(6) prescription of preparation:
Aqueous injection: Calculus Bovis extract 5.0 grams, Moschus extract 2.0 grams, Radix Ginseng extract 15.0 grams, Radix Salviae Miltiorrhizae 10.0 grams;
Infusion solution: Calculus Bovis extract 5.0 grams, Moschus extract 2.0 grams, Radix Ginseng extract 15.0 grams, Radix Salviae Miltiorrhizae 10.0 grams;
Injectable powder: Calculus Bovis extract 5.0 grams, Moschus extract 2.0 grams, Radix Ginseng extract 15.0 grams, Radix Salviae Miltiorrhizae 10.0 grams;
(7) formulation preparation:
The preparation of aqueous injection: the HP-β-CD that gets 30 times of amount Moschus extracts, add the injection water and be made into 40% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 30 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 4 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.5, add 60 ℃ of insulations of 0.2% active carbon 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, sterilize, stop leakage in the roof, be packaged to be 1000 bottles of aqueous injection;
The preparation of infusion solution: the HP-β-CD that gets 30 times of amount Moschus extracts, add the injection water and be made into 40% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 30 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 4 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.5, add 60 ℃ of insulations of 0.2% active carbon 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, 115 ℃ of pressure sterilizings, lamp inspection, be packaged to be 1000 bottles of infusion solutions;
The preparation of injectable powder: the HP-β-CD that gets 30 times of amount Moschus extracts, add the injection water and be made into 40% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 30 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 4 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed; add freeze-dried excipient; transfer pH value to 7.5 with 20% sodium hydroxide; supply volume with water for injection; add 60 ℃ of insulations of 0.2% active carbon 30 minutes; take off charcoal, fine straining, fill, half tamponade, lyophilization, gland, test package obtains 1000 bottles of injectable powder.
Embodiment 3
(1) raw material medicines in portions by weight of the present invention:
Calculus Bovis 10 grams, Moschus 10 grams, Radix Ginseng 150 grams, Radix Salviae Miltiorrhizae 150 grams;
(2) get Moschus, extracted 6 hours, obtain Moschus extract, filter standby with 4 times of 95% ethanol continuous backflow;
(3) get Calculus Bovis, adding 4 times of water gagings decocts 2 times, merge decocting liquid, filter, supernatant adds 0.5% activated carbon decolorizing, solution concentrate under reduced pressure at low temperature to 50 ℃ relative density after the decolouring is 1.08 extractum, adds ethanol again and makes and contain alcohol amount and reach 70%, leaves standstill 24 hours, filter, supernatant decompression recycling ethanol, and to concentrate 50 ℃ of relative densities be 1.08 extractum adds ethanol and makes and contain the alcohol amount and reach 80%, leave standstill cold preservation more than 24 hours, filter, the supernatant decompression recycling ethanol also concentrates, and cold drying obtains Calculus Bovis extract;
(4) Radix Salviae Miltiorrhizae is pulverized, and is that aqueous alkali more than 10 is carried 2 times with pH, and temperature is 90 ℃, each 90 minutes, merge extractive liquid,, centrifugal, get supernatant, being evaporated to 50 ℃ of relative densities is 1.12, transfers pH6.8, adding ethanol makes and contains the alcohol amount and reach 75%, leave standstill, filter, filtrate recycling ethanol is to most, being evaporated to 50 ℃ of relative densities is 1.25, add ethanol again and make the alcohol amount of containing 80%, leave standstill, in solution, by volume add 1% active carbon, stirred 1 hour, filter, filter, filtrate recycling ethanol is to most, the concentrating under reduced pressure drying obtains Radix Salviae Miltiorrhizae extract;
(5) get the Radix Ginseng powder and be broken into coarse powder, add 6 times of amount alcohol reflux of 70% 2 times, extracting solution filters, add water to every milliliter behind the recovery ethanol and contain the 0.9g crude drug, cold preservation 24 hours, centrifugal, D101 macroporous resin adsorption on the supernatant, first washing with 3 times of amounts, reuse 80% ethanol elution is collected 80% ethanol elution, decompression recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.10 extractum, adding ethanol makes and contains alcohol amount and reach more than 80%, cold preservation 24 hours filters, filtrate recycling ethanol, spray drying gets Radix Ginseng extract;
(6) prescription of preparation:
Aqueous injection: Calculus Bovis extract 3.5 grams, Moschus extract 1.3 grams, Radix Ginseng extract 10 grams, Radix Salviae Miltiorrhizae 7 grams;
Infusion solution: Calculus Bovis extract 3.5 grams, Moschus extract 1.3 grams, Radix Ginseng extract 10 grams, Radix Salviae Miltiorrhizae 7 grams;
Injectable powder: Calculus Bovis extract 3.5 grams, Moschus extract 1.3 grams, Radix Ginseng extract 10 grams, Radix Salviae Miltiorrhizae 7 grams;
(7) formulation preparation:
The preparation of aqueous injection: the HP-β-CD that gets 25 times of amount Moschus extracts, add the injection water and be made into 38% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 25 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 2 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.3, add 55 ℃ of insulations of 0.2% active carbon 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, sterilize, stop leakage in the roof, be packaged to be 1000 bottles of aqueous injection;
The preparation of infusion solution: the HP-β-CD that gets 25 times of amount Moschus extracts, add the injection water and be made into 38% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 25 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 2 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.3, add 55 ℃ of insulations of 0.2% active carbon 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, 115 ℃ of pressure sterilizings, lamp inspection, be packaged to be 1000 bottles of infusion solutions;
The preparation of injectable powder: the HP-β-CD that gets 25 times of amount Moschus extracts, add the injection water and be made into 38% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 25 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 2 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed; add freeze-dried excipient; transfer pH value to 7.0 with 20% sodium hydroxide; supply volume with water for injection; add 55 ℃ of insulations of 0.2% active carbon 30 minutes; take off charcoal, fine straining, fill, half tamponade, lyophilization, gland, test package obtains 1000 bottles of injectable powder.
Embodiment 4
(1) raw material medicines in portions by weight of the present invention:
Calculus Bovis 7 grams, Moschus 6 grams, Radix Ginseng 130 grams, Radix Salviae Miltiorrhizae 110 grams;
(2) get Moschus, extracted 5 hours, obtain Moschus extract, filter standby with 3 times of 95% ethanol continuous backflow;
(3) get Calculus Bovis, adding 4 times of water gagings decocts 2 times, merge decocting liquid, filter, supernatant adds 0.5% activated carbon decolorizing, solution concentrate under reduced pressure at low temperature to 50 ℃ relative density after the decolouring is 1.06 extractum, adds ethanol again and makes and contain alcohol amount and reach 70%, leaves standstill 24 hours, filter, supernatant decompression recycling ethanol, and to concentrate 50 ℃ of relative densities be 1.06 extractum adds ethanol and makes and contain the alcohol amount and reach 80%, leave standstill cold preservation more than 24 hours, filter, the supernatant decompression recycling ethanol also concentrates, and cold drying obtains Calculus Bovis extract;
(4) Radix Salviae Miltiorrhizae is pulverized, and is that aqueous alkali more than 10 is carried 2 times with pH, and temperature is 85 ℃, each 65 minutes, merge extractive liquid,, centrifugal, get supernatant, being evaporated to 50 ℃ of relative densities is 1.11, transfers pH6.6, adding ethanol makes and contains the alcohol amount and reach 72%, leave standstill, filter, filtrate recycling ethanol is to most, being evaporated to 50 ℃ of relative densities is 1.22, add ethanol again and make the alcohol amount of containing 79%, leave standstill, in solution, by volume add 1% active carbon, stirred 1 hour, filter, filter, filtrate recycling ethanol is to most, the concentrating under reduced pressure drying obtains Radix Salviae Miltiorrhizae extract;
(5) get the Radix Ginseng powder and be broken into coarse powder, add 6 times of amount alcohol reflux of 65% 2 times, extracting solution filters, add water to every milliliter behind the recovery ethanol and contain the 0.9g crude drug, cold preservation 24 hours, centrifugal, D101 macroporous resin adsorption on the supernatant, first washing with 2 times of amounts, reuse 75% ethanol elution is collected 75% ethanol elution, decompression recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.10 extractum, adding ethanol makes and contains alcohol amount and reach more than 80%, cold preservation 24 hours filters, filtrate recycling ethanol, spray drying gets Radix Ginseng extract;
(6) prescription of preparation:
Aqueous injection: Calculus Bovis extract 2.5 grams, Moschus extract 0.8 gram, Radix Ginseng extract 6.9 grams, Radix Salviae Miltiorrhizae 5.2 grams;
Infusion solution: Calculus Bovis extract 2.5 grams, Moschus extract 0.8 gram, Radix Ginseng extract 6.9 grams, Radix Salviae Miltiorrhizae 5.2 grams;
Injectable powder: Calculus Bovis extract 2.5 grams, Moschus extract 0.8 gram, Radix Ginseng extract 6.9 grams, Radix Salviae Miltiorrhizae 5.2 grams;
(7) formulation preparation:
The preparation of aqueous injection: the HP-β-CD that gets 22 times of amount Moschus extracts, add the injection water and be made into 36% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 22 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 1 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.3, add 52 ℃ of insulations of 0.2% active carbon 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, sterilize, stop leakage in the roof, be packaged to be 1000 bottles of aqueous injection;
The preparation of infusion solution: the HP-β-CD that gets 22 times of amount Moschus extracts, add the injection water and be made into 36% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 22 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 1 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.3, add 52 ℃ of insulations of 0.2% active carbon 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, 115 ℃ of pressure sterilizings, lamp inspection, be packaged to be 1000 bottles of infusion solutions;
The preparation of injectable powder: the HP-β-CD that gets 22 times of amount Moschus extracts, add the injection water and be made into 36% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 22 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 1 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed; add freeze-dried excipient; transfer pH value to 6.9 with 20% sodium hydroxide; supply volume with water for injection; add 52 ℃ of insulations of 0.2% active carbon 30 minutes; take off charcoal, fine straining, fill, half tamponade, lyophilization, gland, test package obtains 1000 bottles of injectable powder.
Embodiment 5
(1) raw material medicines in portions by weight of the present invention:
Calculus Bovis 14 grams, Moschus 13 grams, Radix Ginseng 170 grams, Radix Salviae Miltiorrhizae 190 grams;
(2) get Moschus, extracted 7 hours, obtain Moschus extract, filter standby with 5 times of 95% ethanol continuous backflow;
(3) get Calculus Bovis, adding 5 times of water gagings decocts 2 times, merge decocting liquid, filter, supernatant adds 0.5% activated carbon decolorizing, solution concentrate under reduced pressure at low temperature to 50 ℃ relative density after the decolouring is 1.09 extractum, adds ethanol again and makes and contain alcohol amount and reach 70%, leaves standstill 24 hours, filter, supernatant decompression recycling ethanol, and to concentrate 50 ℃ of relative densities be 1.09 extractum adds ethanol and makes and contain the alcohol amount and reach 80%, leave standstill cold preservation more than 24 hours, filter, the supernatant decompression recycling ethanol also concentrates, and cold drying obtains Calculus Bovis extract;
(4) Radix Salviae Miltiorrhizae is pulverized, and is that aqueous alkali more than 10 is carried 3 times with pH, and temperature is 95 ℃, each 110 minutes, merge extractive liquid,, centrifugal, get supernatant, being evaporated to 50 ℃ of relative densities is 1.14, transfers pH6.9, adding ethanol makes and contains the alcohol amount and reach 78%, leave standstill, filter, filtrate recycling ethanol is to most, being evaporated to 50 ℃ of relative densities is 1.29, add ethanol again and make the alcohol amount of containing 84%, leave standstill, in solution, by volume add 1% active carbon, stirred 1 hour, filter, filter, filtrate recycling ethanol is to most, the concentrating under reduced pressure drying obtains Radix Salviae Miltiorrhizae extract;
(5) get the Radix Ginseng powder and be broken into coarse powder, add 7 times of amount alcohol reflux of 78% 2 times, extracting solution filters, add water to every milliliter behind the recovery ethanol and contain the 0.9g crude drug, cold preservation 24 hours, centrifugal, D101 macroporous resin adsorption on the supernatant, first washing with 3 times of amounts, reuse 88% ethanol elution is collected 88% ethanol elution, decompression recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.10 extractum, adding ethanol makes and contains alcohol amount and reach more than 80%, cold preservation 24 hours filters, filtrate recycling ethanol, spray drying gets Radix Ginseng extract;
(6) prescription of preparation:
Aqueous injection: Calculus Bovis extract 4.2 grams, Moschus extract 1.9 grams, Radix Ginseng extract 14.3 grams, Radix Salviae Miltiorrhizae 9.4 grams;
Infusion solution: Calculus Bovis extract 4.2 grams, Moschus extract 1.9 grams, Radix Ginseng extract 14.3 grams, Radix Salviae Miltiorrhizae 9.4 grams;
Injectable powder: Calculus Bovis extract 4.2 grams, Moschus extract 1.9 grams, Radix Ginseng extract 14.3 grams, Radix Salviae Miltiorrhizae 9.4 grams;
(7) formulation preparation:
The preparation of aqueous injection: the HP-β-CD that gets 29 times of amount Moschus extracts, add the injection water and be made into 38% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 28 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 3 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.4, add 59 ℃ of insulations of 0.2% active carbon 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, sterilize, stop leakage in the roof, be packaged to be 1000 bottles of aqueous injection;
The preparation of infusion solution: the HP-β-CD that gets 28 times of amount Moschus extracts, add the injection water and be made into 39% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 29 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 3 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.4, add 59 ℃ of insulations of 0.2% active carbon 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, 115 ℃ of pressure sterilizings, lamp inspection, be packaged to be 1000 bottles of infusion solutions;
The preparation of injectable powder: the HP-β-CD that gets 29 times of amount Moschus extracts, add the injection water and be made into 39% solution, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 28 minutes, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 3 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed; add freeze-dried excipient; transfer pH value to 7.4 with 20% sodium hydroxide; supply volume with water for injection; add 59 ℃ of insulations of 0.2% active carbon 30 minutes; take off charcoal, fine straining, fill, half tamponade, lyophilization, gland, test package obtains 1000 bottles of injectable powder.
Claims (3)
1. a heart resurrecting injection preparation is characterized in that being made by following weight parts proportioning raw material: Calculus Bovis 6-15, Moschus 5-15, Radix Ginseng 120-180, Radix Salviae Miltiorrhizae 100-200.
2. according to claim 1 described a kind of heart resurrecting injection preparation; its feature is that also its active component is by Calculus Bovis extract 2.0-5.0 weight portion; Moschus extract 0.5-2.0 weight portion, Radix Ginseng extract 6.0-15.0 weight portion, Radix Salviae Miltiorrhizae extract 4.0-10.0 weight portion is made.
3. heart resurrecting injection preparation is characterized in that preparation method may further comprise the steps:
(1) gets Moschus, extracted 4-8 hour, obtain Moschus extract, filter standby with 2-6 times of 95% ethanol continuous backflow;
(2) get Calculus Bovis, adding 3-6 times of water gaging decocts 2 times, merge decocting liquid, filter, supernatant adds 0.5% activated carbon decolorizing, solution concentrate under reduced pressure at low temperature to 50 ℃ relative density after the decolouring is the extractum of 1.05-1.10, adds ethanol again and makes and contain alcohol amount and reach 70%, leaves standstill 24 hours, filter, supernatant decompression recycling ethanol, and concentrate 50 ℃ of extractum that relative density is 1.05-1.10 adds ethanol and makes and contain the alcohol amount and reach 80%, leave standstill cold preservation more than 24 hours, filter, the supernatant decompression recycling ethanol also concentrates, and cold drying obtains Calculus Bovis extract;
(3) Radix Salviae Miltiorrhizae is pulverized, and is that aqueous alkali more than 10 is carried 2-3 time with pH, and temperature is 80-100 ℃, each 60-120 minute, merge extractive liquid,, centrifugal, get supernatant, being evaporated to 50 ℃ of relative densities is 1.10-1.15, transfers pH6.5-7, adding ethanol makes and contains the alcohol amount and reach 70%-80%, leave standstill, filter, filtrate recycling ethanol is to most, being evaporated to 50 ℃ of relative densities is 1.20-1.30, add ethanol again and make and contain alcohol amount 75%-85%, leave standstill, in solution, by volume add 1% active carbon, stirred 1 hour, filter, filter, filtrate recycling ethanol is to most, the concentrating under reduced pressure drying obtains Radix Salviae Miltiorrhizae extract;
(4) get the Radix Ginseng powder and be broken into coarse powder, add the alcohol reflux 2 times that 5-8 doubly measures 60%-80%, extracting solution filters, add water to every milliliter behind the recovery ethanol and contain the 0.8-1g crude drug, cold preservation 24 hours, centrifugal, D101 macroporous resin adsorption on the supernatant, the washing of doubly measuring earlier with 2-3, reuse 70%-90% ethanol elution, collect the 70%-90% ethanol elution, decompression recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.10 extractum adds ethanol and makes and contain the alcohol amount and reach more than 80%, cold preservation 24 hours, filter, filtrate recycling ethanol, spray drying gets Radix Ginseng extract;
(5) preparation of preparation:
The preparation of aqueous injection: get HP-β-CD that 20-30 doubly measures Moschus extract, add the solution that the injection water is made into 35-40%, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 20-30 minute, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 0-4 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.2-7.5, add 0.2% active carbon 50-60 ℃ of insulation 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, sterilize, stop leakage in the roof, be packaged to be aqueous injection;
The preparation of infusion solution: get HP-β-CD that 20-30 doubly measures Moschus extract, add the solution that the injection water is made into 35-40%, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 20-30 minute, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 0-4 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed, supply volume with water for injection, transfer pH value to 7.2-7.5, add 0.2% active carbon 50-60 ℃ of insulation 30 minutes with 20% sodium hydroxide, take off charcoal, fine straining, fill, 115 ℃ of pressure sterilizings, lamp inspection, be packaged to be infusion solution;
The preparation of injectable powder: get HP-β-CD that 20-30 doubly measures Moschus extract, add the solution that the injection water is made into 35-40%, filter, charcoal is taken off in 90 ℃ of insulations of the active carbon of adding 0.5% 20-30 minute, and filtrate is cooled to 50 ℃, the 3-methylcyclopentadecanol extract is slowly dropped to wherein, dropping while stirring makes and is uniformly dispersed, airtight shearing enclose 8 hours, and it is standby that enclose liquid low-temperature reduced-pressure is flung to part ethanol; Radix Ginseng extract, Radix Salviae Miltiorrhizae extract mixed pulverize, add the dissolving of injection water, boiled 15 minutes, put naturally cold, 0-4 ℃ of cold preservation 24 hours, filtration, it is 10000 ultrafilter membrane ultrafiltration that filtered solution is crossed molecular cut off, ultrafiltrate is standby; With the Calculus Bovis extract saturated dissolve with ethanol of sodium hydroxide, it is an amount of, standby to add the injection water; Above Moschus enclose liquid, ultrafiltrate, Calculus Bovis solution are mixed; add freeze-dried excipient; transfer pH value to 6.8-7.5 with 20% sodium hydroxide; supply volume with water for injection; add 0.2% active carbon 50-60 ℃ of insulation 30 minutes; take off charcoal, fine straining, fill, half tamponade, lyophilization, gland, test package obtains injectable powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2005100870180A CN1899369A (en) | 2005-07-22 | 2005-07-22 | Heart resurrecting injection preparation and its preparing method |
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| CNA2005100870180A CN1899369A (en) | 2005-07-22 | 2005-07-22 | Heart resurrecting injection preparation and its preparing method |
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| CN1899369A true CN1899369A (en) | 2007-01-24 |
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| CNA2005100870180A Pending CN1899369A (en) | 2005-07-22 | 2005-07-22 | Heart resurrecting injection preparation and its preparing method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102764280A (en) * | 2011-05-06 | 2012-11-07 | 秦引林 | Bezoar and musk containing pharmaceutical composition and its application |
| CN114522190A (en) * | 2020-11-20 | 2022-05-24 | 上海和黄药业有限公司 | Pharmaceutical composition for resisting myocardial ischemia injury and preparation method and application thereof |
-
2005
- 2005-07-22 CN CNA2005100870180A patent/CN1899369A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102764280A (en) * | 2011-05-06 | 2012-11-07 | 秦引林 | Bezoar and musk containing pharmaceutical composition and its application |
| CN114522190A (en) * | 2020-11-20 | 2022-05-24 | 上海和黄药业有限公司 | Pharmaceutical composition for resisting myocardial ischemia injury and preparation method and application thereof |
| CN114522190B (en) * | 2020-11-20 | 2023-06-27 | 上海和黄药业有限公司 | Pharmaceutical composition for resisting myocardial ischemia injury, and preparation method and application thereof |
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