CN1843455A - Pharmaceutical composition, its preparation method and usage - Google Patents
Pharmaceutical composition, its preparation method and usage Download PDFInfo
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- CN1843455A CN1843455A CN 200510063087 CN200510063087A CN1843455A CN 1843455 A CN1843455 A CN 1843455A CN 200510063087 CN200510063087 CN 200510063087 CN 200510063087 A CN200510063087 A CN 200510063087A CN 1843455 A CN1843455 A CN 1843455A
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- ginseng rubra
- radix ginseng
- radix ophiopogonis
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Abstract
The invention discloses a pharmaceutical composition, its preparing process and use, wherein the composition comprises red ginseng extract and ophiopogon root extract by a predetermined proportion, and can be used for treating cardiogenic shock and hemorrhagic shock.
Description
Invention field
The present invention relates to a kind of pharmaceutical composition and its production and use, particularly a kind of pharmaceutical composition that is used for the treatment of shock, coronary heart disease, angina pectoris and ischemia apoplexy and its production and use.
Background technology
SHENMAI ZHUSHEYE nearly 30 years history of going on the market at home has a plurality of producers producing this kind now, and has obtained good social benefit and economic benefit.Country has strengthened the dynamics to the injection safety requirements in recent years, and the production technology and the quality control of injection are also had higher requirement.SHENMAI ZHUSHEYE be with clean medical material be raw material through extraction and simple purification after the ejection preparation made, production technology is backward relatively, the control of injection difficult quality, the curative effect instability that causes preparation, and the invalid components in the preparation enters and is easy to produce untoward reaction in the body, even can endanger patient's life.SHENMAI ZHUSHEYE also will could be used through dilution in clinical use more in addition, causes secondary pollution easily.Along with extracting and the raising of purification technique and, the deep development of this kind has been become possibility to the further investigation of this kind.The present invention is by adopting the macroporous adsorbent resin technology, and the effective site of purification Radix Ginseng and Radix Ophiopogonis improves content of effective, is made into the compositions of effective extract, overcomes curative effect and quality instability that clean medical material directly feeds intake and exists, the shortcoming of poor stability.
Summary of the invention
One object of the present invention is to disclose a kind of pharmaceutical composition; Another object of the present invention is to disclose a kind of pharmaceutical composition that is used for the treatment of shock, coronary heart disease, angina pectoris and ischemia apoplexy; The 3rd purpose of the present invention is to disclose a kind of preparation of drug combination method; The 4th purpose of the present invention is to disclose a kind of purposes of pharmaceutical composition.
The crude drug of pharmaceutical composition of the present invention is formed and proportioning following (by weight):
Radix Ginseng Rubra extract 1-16 weight portion
Radix Ophiopogonis extract 1-2 weight portion
It is (by weight) that the crude drug of pharmaceutical composition of the present invention is formed optimum ratio:
Radix Ginseng Rubra extract 16 weight portions
Radix Ophiopogonis extract 1 weight portion
It is (by weight) that the crude drug of pharmaceutical composition of the present invention is formed optimum ratio:
Radix Ginseng Rubra extract 4 weight portions
Radix Ophiopogonis extract 1 weight portion
It is (by weight) that the crude drug of pharmaceutical composition of the present invention is formed optimum ratio:
Radix Ginseng Rubra extract 2 weight portions
Radix Ophiopogonis extract 1 weight portion
It is (by weight) that the crude drug of pharmaceutical composition of the present invention is formed optimum ratio:
Radix Ginseng Rubra extract 5 weight portions
Radix Ophiopogonis extract 1 weight portion
It is (by weight) that the crude drug of pharmaceutical composition of the present invention is formed optimum ratio:
Radix Ginseng Rubra extract 3 weight portions
Radix Ophiopogonis extract 1 weight portion
Radix Ginseng Rubra extract provided by the invention, extraction, purification obtain from the Radix Ginseng Rubra medical material, and the content of its total saponins is more than 50%.Radix Ophiopogonis total saponins provided by the invention extracts from the Radix Ophiopogonis medical material, purification obtains, and the content of its total saponins is more than 50%.
The present invention also provides a kind of preparation of drug combination method:
The Radix Ginseng Rubra medical material is thinly sliced, and the ethanol that adds 40～100% (v/v) of 4～10 times of crude drug amounts carries out reflux 3～6 times, each half an hour; Merge extractive liquid,, decompression and solvent recovery; The concentrated solution that obtains is injected macroporous adsorptive resins, doubly measure the purified water eluting of column volume earlier with 4-10, reuse 5-12 doubly measures column volume 10-30% ethanol elution, discards eluent, uses the 50-90% ethanol elution then, collects the eluent that 4-8 doubly measures column volume; With the eluent that obtains, reclaim ethanol and concentrated, drying is pulverized, and promptly gets Radix Ginseng Rubra extract.Get medical material Radix Ophiopogonis, pulverize, the ethanol that adds 50～100% (v/v) of 4～10 times of crude drug amounts carries out heating and refluxing extraction 1～4 time, each 0.5-2 hour; Merge extractive liquid,, decompression and solvent recovery; The concentrated solution that obtains is injected macroporous adsorptive resins, doubly measure the purified water eluting of column volume earlier with 2-6, reuse 2-6 doubly measures column volume 30-50% ethanol elution, discards eluent, uses the 70-90% ethanol elution then, collects the eluent that 1-6 doubly measures column volume; The eluent that obtains is reclaimed ethanol and concentrated, and drying is pulverized, and promptly gets Radix Ophiopogonis extract.In the ratio of the invention described above pharmaceutical composition, get Radix Ginseng Rubra extract and Radix Ophiopogonis extract, add adjuvant, be prepared into clinical acceptable forms: tablet, capsule, pill, granule, transfusion, freeze-dried powder.
In preparation Radix Ginseng Rubra extract and Radix Ophiopogonis extract process, described etoh solvent can be substituted by water, methanol, acetone; Described heating and refluxing extraction mode can be substituted by dipping, percolation; Described macroporous adsorbent resin comprises: D series, HPD series, SP series and NKA type and AB-8 type for being crosslinked nonpolar, low pole of primary raw material or polar resin with styrene and divinylbenzene; The preferred D101 of D series, the preferred HPD100 of HPD series, the preferred HP-20 of SP series; Described drying mode can be oven dry, vacuum drying, spray drying or lyophilization.
The present invention is further purified the effective ingredient that curative effect is clear and definite in the existing SHENMAI ZHUSHEYE, provide that a kind of preparation technology is more advanced, proportioning more science, the more controlled pharmaceutical composition of quality, reduced dosage, curative effect of medication and stability have been improved, reduced toxic and side effects, the various preparation curative effects of making are more reliable, and safety is higher, use more conveniently, character is more stable.
Pharmacodynamics to this pharmaceutical composition has partly carried out preliminary study, the result shows that said composition has anti-hemorrhagic shock, anti-cardiogenic shock effect: the contractility that can improve heart failure rat model cardiac muscle, reduce myocardial oxygen consumption, the expansion peripheral blood vessel reduces Peripheral resistance; Can improve myocardial ischemia; Mice anoxia enduring model time-to-live and mouse anti-reflecting fatigue model swimming time are prolonged, these presentation of results, said composition is applicable to cardiogenic shock, hemorrhagic shock and the acute heart failure that caused by shock, diseases such as coronary heart disease, angina pectoris, myocardial infarction.Following experimental example is used to further specify the present invention:
The proportioning screening test of experimental example 1 compositions
(1) to the comparison of myocardial ischemia effect
40 of SD rats, male, body weight 250～350g is divided into 4 groups at random: blank group (waiting the capacity normal saline), Rhizoma Zingiberis Recens A group (32: 1,20mg/kg), the B group (16: 1,20mg/kg), the C group (4: 1,20mg/kg), the D group (2: 1,20mg/kg).6/group, sodium pentobarbital (30mg/Kg) intraperitoneal injection of anesthesia, it is fixing to lie on the back, and tracheal intubation connects respirator, tidal volume 1ml, 14 times/min of frequency, respiratory quotient 3: 1.Regulate physiograph, the right common carotid artery intubate connects pressure converter and measures systolic arterial pressure (SBP) diastolic pressure (DBP).Connect limb lead and measure ECGII, treat stable back each parameter normal value of record.Left side chest unhairing sterilization, along left mid-clavicular line, open breast at the 3rd or the 4th intercostal, expose heart, cut off pericardium, the light right side thorax of pressing, extruding heart slightly, apart from the about 2mm of pulmonary conus root, is sign with the great cardiac vein at the left auricle lower edge, sewing needle be will can't harm and the about 0.5mm of cardiac muscle, ligation ramus descendens anterior arteriae coronariae sinistrae thrust.Send heart back to thoracic cavity immediately, breast is massaged outward, sews up the thoracic cavity, treats to pull out respirator after autonomous respiration recovers.Intravenous administration is thereafter 5,10,20,30,40,50,60,90,120min writes down every index respectively.
The result:
The left coronary artery joint is rolled and is made the rat heart muscle ischemia model, and A, B, C, D four medicines are screened.Take temperature from the variation of rat electrocardiogram J point, organize a t check, the result shows, A, B, C, D have the effect (except indivedual time point J points risings of A) that certain reduction J order, and A, B, D effect are not obvious, but B, D slightly are better than A, compare A, B, D not statistically significant with matched group; C has the effect that remarkable reduction J is ordered, and compares with matched group, has statistical significance (P＜0.05, P＜0.01), and demonstration can improve myocardial ischemia.The results are shown in Table 1.
(2) pentobarbital is caused the comparison of rat shock effect
The healthy SD rat, body weight 250～350g, male 40.Be divided into 4 groups at random: matched group (giving the equal-volume normal saline), Rhizoma Zingiberis Recens A group (20mg/kg), B organize (20mg/kg) and C amount group (20mg/kg), and the D group (2: 1,20mg/kg), 10 every group.After rat was weighed, with 3% pentobarbital sodium anesthesia, the anti-back of the body was fixing, separates right common carotid artery and left femoral artery vein, does arterial cannulation, connects eight road physiograph pressure transducers, and venous cannulation is treated to pentobarbital sodium, connects electrocardio II and leads.Write down following index normal value: left indoor systolic pressure (LVSP), systolic arterial pressure (SBP).Pentobarbital sodium 0.5ml with microsyringe 0.15ml/min instillation 3%, changing is that 0.2% pentobarbital sodium 0.15ml/min, the 3～5ml that instils activates pulse pressure and drops to 50% again, and dP/dt drops to about 30%, keeps 10min, be heart failure, every index during the record heart failure.Through the tail intravenously administrable, administration 5min, administration finish the back and finish back 5,10,15,20,30min writes down every index.Calculate each index meansigma methods standard deviation, organize a t check, judge significant difference at each time point and matched group.
The result:
By table 2,3 results as can be seen, cause left indoor systolic pressure (LVSP), systolic arterial pressure (SBP) decline that rat shock causes for pentobarbital, living arteries and veins B, C, D sample sets 20mg/kg can significantly show the decline (P＜0.05) that suppresses animal SBP, LVSP, the time that remarkable drug effect takes place greatly after 10-20min, the effective trend of A sample.Comparatively speaking, the effect of C, D sample slightly is better than the B sample.
Compositions proportioning screening conclusion:
By above-mentioned two tests as can be seen, Radix Ginseng Rubra extract: (16: 1-2: scope 1) is to improving the rat heart muscle ischemia and the shock tool has certain effect, wherein with 4: 1 best results for Radix Ophiopogonis extract.
Influence (n=6, x ± s, unit: mv) that table 1A, B, C, D change coronary ligation rat electrocardiogram J point
| Group | Time after the administration (min) | ||||||||
| 5 | 10 | 20 | 30 | 40 | 50 | 60 | 90 | 120 | |
| Normal saline | -0.021± O.020 | -0.014± 0.04l | -0.029± 0.039 | -0.043± 0.039 | -0.029± 0.047 | -0.029± 0.053 | -0.021± 0.054 | -0.007± 0.069 | 0.000± 0.076 |
| A 20mg/kg | 0.006± 0.042 | 0.012± 0.037 | 0.179± 0.030 | 0.006± 0.047 | -0.006± 0.035 | 0.006± 0.042 | -0.006± 0.035 | 0.006± 0.042 | -0.006± 0.042 |
| B 20mg/kg | 0.000± 0.111 | 0.060± 0.12l | 0.060± 0.121 | 0.089± 0.127 | 0.077± 0.13l | 0.083± 0.140 | 0.095± 0.153 | 0.095± 0.142 | 0.101± 0.140 |
| C 20mg/kg | 0.083± 0.084* | 0.10l± 0.089* | 0.113± 0.039** | 0.113± 0.076** | O.089± 0.067** | 0.089± 0.044** | 0.083± 0.037** | 0.089± 0.037* | 0.083± 0.029* |
| D 20mg/kg | 0.0042± 0.053 | 0.044± 0.038 | 0.101± 0.033 | 0.097± 0.052 | 0.075± 0.045 | 0.086± 0.084 | 0.075± 0.048 | 0.087± 0.085 | 0.097± 0.076 |
Annotate: each time point and normal saline group are organized t check * P＜0.05 * * P＜0.01 behind the medicine
Table 2. pair pentobarbital causes influence (n=6, the x ± s) of rat shock SBP (KPa)
| Group | Normally | After the shock | Time after the administration (min) | |||
| 5 | 10 | 20 | 30 | |||
| Blank group A group B group C group D group | 18.62±4.64 19.68±3.15 19.75±4.11 19.94±3.65 19.78±3.74 | 9.82±2.23 8.85±2.32 9.02±2.51 8.79±2.23 8.81±2.31 | 10.02±2.01 10.08±3.00 10.04±2.21 9.82±2.23 9.95±2.35 | 9.90±2.05 10.57±2.03 11.89±3.02 10.73±2.12 10.56±2.35 | 9.06±3.19 9.97±2.31 12.72±2.23* 11.57±2.34* 11.85±2.43* | 9.50±2.02 9.68±3.76 12.98±2.45* 13.99±3.70* 13.09±3.45* |
Annotate: compare * P＜0.05, * * P＜0.01 with the blank group
Table 3 pair pentobarbital causes influence (n=6, the x ± s) of rat shock LVSP (KPa)
| Group | Normally | After the shock | Time after the administration (min) | |||
| 5 | 10 | 20 | 30 | |||
| Blank group A group B group C group D group | 20.32±5.76 22.40±6.86 21.12±4.76 22.04±6.87 21.53±5.65 | 9.35±4.22 10.67±4.23 9.96±4.23 9.97±2.20 9.78±2.23 | 9.58±3.16 10.96±2.75 10.99±3.15 10.98±2.43 10.96±2.51 | 9.70±2.56 12.196±2.055 12.99±2.48* 13.98±2.05** 13.02±2.125** | 9.58±2.56 12.91±2.60* 13.02±2.24* 14.30±2.64* 12.95±3.25* | 9.62±3.23 10.58±3.45 13.27±2.09* 15.22±3.52* 14.01±3.60* |
Annotate: compare * P＜0.05, * * P＜0.01 with the blank group
The screening of experimental example 2 pharmacodynamicss
(1) influence of the cardiogenic shock that anesthetized open-chest dog ligation arteria coronaria is caused
30 of hybrid dogs are divided into 5 groups, 6 every group.Matched group waits the contrast of capacity solvent, and the positive drug group gives SHENMAI ZHUSHEYE 3.2ml/kg, and (the 640mg crude drug/kg), experiment component is that the Rhizoma Zingiberis Recens compositions (Radix Ginseng Rubra extract: 4mg/kg dosage group Radix Ophiopogonis extract 4: 1), all slowly instil by employing.With pentobarbital sodium 30mg/kg i.v. anesthesia, back of the body position is fixing, and skin of neck cuts, and tracheal intubation connects electric pulmotor, separates right carotid, connects the AP-601G amplifier, measures blood pressure.Experiment is taken off heart after finishing, and claims to weigh whole-heartedly, cuts off trunk root and atrium along coronary sulcus, claims left ventricle heavy.Be cut into 5 with left ventricle is cross-section equably, place nitro tetrazole orchid (N-BT) dye liquor, 15min dyes in 37 ℃ of constant water bath box.Infarcted region is not painted, and non-infarcted region is dyed by NBT and is blueness.Cut off each myocardium sheet and be colored non-infarcted region cardiac muscle, undyed infarcted myocardium is weighed, obtain infarction size heavily respectively divided by heavy and ventricle whole-heartedly and account for heavy whole-heartedly and the heavy % of ventricle.Get blood from femoral vein, survey aspartate aminotransferase (AST), creatine phosphokinase (CPK) and lactic acid dehydrogenase (LDH) value as being worth before the administration, behind the record 240min, are got blood thought-read flesh three enzymes for the second time.(x ± s) expression uses the mean significance of difference between t check judgement group to all experimental datas with means standard deviation.
The result: Rhizoma Zingiberis Recens compositions (4mg/kg) has anti-cardiogenic shock effect, can reduce the content of LDH, AST and CPK in the ischemic myocardium serum, and the Rhizoma Zingiberis Recens compositions has the effect of dwindling myocardial infarction area.See Table 4.
Table 4 Rhizoma Zingiberis Recens compositions to the influence of myocardial infarction dogs myocardial infarction area (X ± S, n=6)
| Group | Dosage (mg/kg) | Infraction/(%) whole-heartedly | Infraction/left the heart (%) |
| Normal saline group SHENMAI ZHUSHEYE Rhizoma Zingiberis Recens compositions | ----640 (crude drug) 4 | 10.76±1.628 8.26±1.771* 8.42±1.666* | 16.03±2.425 12.28±2.427* 12.58±2.475* |
(2) to the influence of rat heart failure model due to the pentobarbital sodium
The healthy SD rat, body weight 250～350g, male 50.Be divided into 5 groups at random: matched group (give equal-volume solvent contrast), SHENMAI ZHUSHEYE (400mg crude drug/kg), Rhizoma Zingiberis Recens composition dosage group (Radix Ginseng Rubra extract: Radix Ophiopogonis extract 3: 1) (4mg/kg), 10 every group.After rat was weighed, with 3% pentobarbital sodium anesthesia, the anti-back of the body was fixing, separates right common carotid artery and left femoral artery vein, does arterial cannulation, connects eight road physiograph pressure transducers, and venous cannulation is treated to pentobarbital sodium, connects electrocardio II and leads.Write down following index normal value: left indoor systolic pressure (LVSP), the maximum rising+dP/dt of left indoor pressure, systolic arterial pressure (SBP), auterial diastole are pressed (DBP).Pentobarbital sodium 0.5ml with microsyringe 0.15ml/min instillation 3%, changing is that 0.2% pentobarbital sodium 0.15ml/min, the 3～5ml that instils activates pulse pressure and drops to 50% again, and dP/dt drops to about 30%, keeps 10min, be heart failure, every index during the record heart failure.Through the tail intravenously administrable, administration 5min, administration finish the back and finish back 5,10,15,20,30min writes down every index.Calculate each index meansigma methods standard deviation, organize a t check, judge significant difference at each time point and matched group.
The result:
A. to the effect of heart failure rat LVSP due to the pentobarbital sodium
The effect of rat heart failure model LVSP due to the table 5 pair pentobarbital sodium
Annotate: compare * P＜0.05 with matched group, * * P＜0.01
Table 5 is the result show, Rhizoma Zingiberis Recens compositions administration group make heart failure animal LVSP after administration 5,10,15,20,30min all raises, and compares with matched group at each time point, and significant difference (* P＜0.05 or * * P＜0.0) is all arranged.Show that the Rhizoma Zingiberis Recens compositions has the contractility that strengthens left chamber, strengthens the blood effect of penetrating.
B. to the effect of the intrinsic pressure maximum climbing speed+dp/dt of heart failure rat left chamber due to the pentobarbital sodium
The effect of rat heart failure model+dp/dt due to the table 6 pair pentobarbital sodium
Table 6 is the result show, each administration group+dp/dt is after administration finishes and finish back 5,10,15,20,30min all raises, and compares with matched group at each time point, and significant difference (* P＜0.05 or * * P＜0.01) is all arranged.
(3) to the influence of platelet aggregation
Table 7 Rhizoma Zingiberis Recens compositions is to the influence of platelet aggregation
| Group | Assemble suppression ratio (%) |
| Blank group positive controls (SHENMAI ZHUSHEYE of 0.5mg/ml) Rhizoma Zingiberis Recens compositions (4: 1,0.4mg/ml) Rhizoma Zingiberis Recens compositions (3: 1,0.4mg/ml) the Rhizoma Zingiberis Recens compositions (5: 1,0.4mg/ml) | ------ 43.19 54.39 58.96 49.15 |
Annotate: compare * P＜0.05, * * P＜0.01 with the blank group
The result shows that the Rhizoma Zingiberis Recens compositions has the effect of good antiplatelet aggregation.
Embodiment 1: the preparation of Rhizoma Zingiberis Recens ordinary tablet
Get the Radix Ginseng Rubra medical material, 50% the alcohol heating reflux that adds 6 times of amounts of crude drug extracted 0.5 hour, filtered filtrate for later use, medicinal residues add 50% ethanol extraction 4 times of 6 times of amounts again, each 0.5 hour, filter, merge four times filtrate, concentrating under reduced pressure, concentrated solution is placed to room temperature, injects D101 macroporous adsorptive resins (medical material and dried resin ratio are 3: 1) slowly, earlier with 10 times of deionized water eluting of measuring column volumes, 5 times of amounts of reuse column volume, 30% ethanol elution, discard 30% eluent, use 70% ethanol elution then, collect 60% eluent of 6 times of amount column volumes, reclaim ethanol and concentrated, the concentrated solution vacuum drying is pulverized, and promptly gets Radix Ginseng Rubra extract.Get medical material Radix Ophiopogonis, pulverize, 90% the alcohol heating reflux that adds 10 times of amounts of crude drug extracted 2 hours, filtered filtrate for later use.90% the alcohol heating reflux that residue adds 6 times of amounts again extracts and extracted twice in 1 hour, filters respectively, merges three times filtrate, concentrating under reduced pressure.Concentrated solution is placed to room temperature, slowly inject NKA macroporous adsorptive resins (medical material and dried resin ratio are 3: 1), with the deionized water eluting of 3 times of bed volumes, 3 times of bed volume 30% ethanol elutions of reuse discard 30% ethanol elution earlier, use 80% ethanol elution then, collect 80% eluent of 4 times of bed volumes, reclaim ethanol, vacuum drying, pulverize, promptly get Radix Ophiopogonis extract.
Radix Ginseng Rubra extract 85g
Radix Ophiopogonis extract 5.31g
Starch 100g
The polyvinylpyrrolidone alcoholic solution is an amount of
Magnesium stearate 1%
Make 1000
With Radix Ginseng Rubra extract, Radix Ophiopogonis extract, starch mix homogeneously, with polyvinylpyrrolidone alcoholic solution system soft material, 18 mesh sieves are granulated, dry back granulate, the magnesium stearate of adding 1%, mixing, tabletting.
Embodiment 2: the preparation of Rhizoma Zingiberis Recens dispersible tablet
Get the Radix Ginseng Rubra medical material, pulverize, 60% the alcohol heating reflux that adds 10 times of amounts of crude drug extracted 1 hour, filter, and filtrate for later use, medicinal residues add 60% ethanol extraction 2 times of 6 times of amounts again, and each 1 hour, filter, merge three times filtrate, concentrating under reduced pressure.Concentrated solution is placed to room temperature, slowly inject NKA macroporous adsorptive resins (medical material and dried resin ratio are 3: 1), with the deionized water eluting of 8 times of amount column volumes, 8 times of amounts of reuse column volume, 20% ethanol elution discards 20% eluent earlier, use 50% ethanol elution then, collect 50% eluent of 8 times of amount column volumes, reclaiming ethanol and being concentrated into relative density is 1.10～1.20 (50 ℃), and concentrated solution is vacuum drying below 50 ℃, crushing screening promptly gets Radix Ginseng Rubra extract; Get medical material Radix Ophiopogonis, pulverize, 70% the alcohol heating reflux that adds 6 times of amounts of crude drug extracted 1 hour, filtered filtrate for later use.70% the alcohol heating reflux that residue adds 6 times of amounts again extracts twice, each 1 hour, filter, merge three times filtrate, concentrating under reduced pressure, slowly inject AB-8 macroporous adsorptive resins (first deionized water eluting with 2 times of bed volumes, 6 times of bed volume 50% ethanol elutions of reuse, discard 50% ethanol elution, use 70% ethanol elution then, collect 70% eluent of 1 times of bed volume, reclaiming ethanol and being concentrated into relative density is 1.15～1.25 (50 ℃), vacuum drying is pulverized, and promptly gets Radix Ophiopogonis extract.
Radix Ginseng Rubra extract 85g
Radix Ophiopogonis extract 42.5g
Lactose 100g
2% mucialga of arabic gummy is an amount of
Magnesium stearate 1%
Make 1000
With Radix Ginseng Rubra extract, Radix Ophiopogonis extract, lactose mix homogeneously, with 2% mucialga of arabic gummy system soft material, 18 mesh sieves are granulated, dry back granulate, the magnesium stearate of adding 1%, mixing, tabletting.
Embodiment 3: the preparation of Rhizoma Zingiberis Recens oral cavity disintegration tablet
Get the Radix Ginseng Rubra medical material, pulverize, 60% the alcohol heating reflux that adds 4 times of amounts of crude drug extracted 0.5 hour, filter, filtrate for later use, medicinal residues add 60% ethanol extraction 4 times of 4 times of amounts, each 0.5 hour again, filter, merge four times filtrate, concentrating under reduced pressure, concentrated solution is placed to room temperature, slowly inject HPD100 macroporous adsorptive resins (medical material and dried resin ratio are 4: 1), with the deionized water eluting of 6 times of amount column volumes, 10 times of amounts of reuse column volume, 10% ethanol elution discards 10% eluent earlier, use 60% ethanol elution then, collect 60% eluent of 4 times of amount column volumes, reclaim ethanol and concentrate spray drying, pulverize, promptly get Radix Ginseng Rubra extract; Get medical material Radix Ophiopogonis, pulverize, 50% the alcohol heating reflux that adds 8 times of amounts of crude drug extracted 2 hours, filtered filtrate for later use.50% the alcohol heating reflux that residue adds 6 times of amounts again extracts 3 times, each 1 hour, filter, merge three times filtrate, concentrating under reduced pressure, concentrated solution is placed to room temperature, injects HPD100 macroporous adsorptive resins (medical material and dried resin ratio are 3: 1) slowly, first deionized water eluting with 6 times of bed volumes, 5 times of bed volume 40% ethanol elutions of reuse, discard 40% ethanol elution, use 90% ethanol elution then, collect 90% eluent of 3 times of bed volumes, reclaim ethanol, vacuum drying is pulverized, and promptly gets Radix Ophiopogonis extract.
Radix Ginseng Rubra extract 85g
Radix Ophiopogonis extract 21.25g
Mannitol 400g
Microcrystalline Cellulose 50g
Micropowder silica gel 5%
Magnesium stearate 1%
Make 1000
With Radix Ginseng Rubra extract, Radix Ophiopogonis extract, mannitol, microcrystalline Cellulose, micropowder silica gel, magnesium stearate mix homogeneously, direct compression.
Embodiment 4: the preparation of Rhizoma Zingiberis Recens slow releasing tablet
Radix Ginseng Rubra extract 170g
Radix Ophiopogonis extract 5.31g
Hydroxypropyl emthylcellulose 200g
The ethyl cellulose alcoholic solution is an amount of
Magnesium stearate 1%
Make 1000
With Radix Ginseng Rubra extract, Radix Ophiopogonis extract, hydroxypropyl emthylcellulose mix homogeneously, with ethyl cellulose alcoholic solution system soft material, 18 mesh sieves are granulated, dry back granulate, the magnesium stearate of adding 1%, mixing, tabletting.
Embodiment 5: the preparation of capsule with red ginseng and lilyturf root
Radix Ginseng Rubra extract 85g
Radix Ophiopogonis extract 21.25g
Microcrystalline Cellulose 100g
Magnesium stearate 1%
Make 1000
With Radix Ginseng Rubra extract, Radix Ophiopogonis extract, microcrystalline Cellulose, magnesium stearate mix homogeneously, fill capsule.
Embodiment 6: the preparation of Rhizoma Zingiberis Recens granule
Radix Ginseng Rubra extract 85g
Radix Ophiopogonis extract 28.33g
Starch 1800g
The polyvinylpyrrolidone alcoholic solution is an amount of
Make 1000 bags
With Radix Ginseng Rubra extract, Radix Ophiopogonis extract, starch mix homogeneously, with polyvinylpyrrolidone alcoholic solution system soft material, 14 mesh sieves are granulated, dry pack.
Embodiment 7: the preparation of Rhizoma Zingiberis Recens pill
Radix Ginseng Rubra extract 85g
Radix Ophiopogonis extract 17g
Starch 100g
Make 1000 of capsules
With Radix Ginseng Rubra extract, Radix Ophiopogonis extract, starch mix homogeneously, make the micropill that particle diameter is about 1.5mm with agitation procedure, encapsulated.
Embodiment 8: the preparation of ginseng and ophiopogon root dripping pill agent
Radix Ginseng Rubra extract 85g
Radix Ophiopogonis extract 21.25g
Polyethylene glycol 6000 200g
Make 1000 bottles of bottles
Polyethylene glycol 6000 is put in the water-bath fusion fully, adds Radix Ginseng Rubra extract, Radix Ophiopogonis extract, stirs to make evenly, keeps 80 ℃ to splash in 15 ℃ of liquid paraffin and become ball, bottles.
Embodiment 9: the preparation of Rhizoma Zingiberis Recens injection
Radix Ginseng Rubra extract 17g
Radix Ophiopogonis extract 3.4g
Methionine 50g
HYDROXYPROPYL BETA-CYCLODEXTRIN 40g
Water for injection 10000ml
Make 1000
Radix Ginseng Rubra extract, Radix Ophiopogonis extract are dissolved in proper amount of water for injection, respectively methionine and HYDROXYPROPYL BETA-CYCLODEXTRIN are dissolved in above-mentioned solution again, the active carbon of adding 0.2%, desuperheating is former, regulates pH to 8.0, aseptic filtration with sodium hydroxide solution, adding injection is diluted with water to volume required, embedding, every 10ml, but with method also fill become 2ml, 5ml, 50ml.
Embodiment 10: the preparation of ginseng freeze-drying powdery injection
Radix Ginseng Rubra extract 17g
Radix Ophiopogonis extract 4.25g
Water for injection 2000ml
Make 1000
Radix Ginseng Rubra extract, Radix Ophiopogonis extract are dissolved in proper amount of water for injection, add 0.2% active carbon, desuperheating is former, aseptic filtration, add injection be diluted with water to volume required, fill, every fill volume is 2ml, lyophilizing.
Embodiment 11: the preparation of Rhizoma Zingiberis Recens transfusion
Radix Ginseng Rubra extract 85g
Radix Ophiopogonis extract 21.25g
Methionine 1250g
PEG400 12500ml
Pin glucose 12500g
Water for injection 237500ml
Make 1000 bottles
Radix Ginseng Rubra extract, Radix Ophiopogonis extract are dissolved in proper amount of water for injection with, PEG400, respectively methionine and pin are dissolved in above-mentioned solution with glucose again, regulate pH to 8.0 with sodium hydroxide solution, the ultrafiltration desuperheating is former, aseptic filtration, add the injection be diluted with water to volume required, fill, every bottle of 250ml, but with method also fill become 100ml.
Claims (10)
1, a kind of pharmaceutical composition for the treatment of shock, coronary heart disease, angina pectoris, ischemia apoplexy is characterized in that this pharmaceutical composition made by following raw medicaments in portion by weight:
Radix Ginseng Rubra extract 1-16 weight portion
Radix Ophiopogonis extract 1-2 weight portion.
2, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition made by following raw medicaments in portion by weight:
Radix Ginseng Rubra extract 16 weight portions
Radix Ophiopogonis extract 1 weight portion.
3, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition made by following raw medicaments in portion by weight:
Radix Ginseng Rubra extract 4 weight portions
Radix Ophiopogonis extract 1 weight portion.
4, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition made by following raw medicaments in portion by weight:
Radix Ginseng Rubra extract 2 weight portions
Radix Ophiopogonis extract 1 weight portion.
5, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition made by following raw medicaments in portion by weight:
Radix Ginseng Rubra extract 5 weight portions
Radix Ophiopogonis extract 1 weight portion.
6, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition made by following raw medicaments in portion by weight:
Radix Ginseng Rubra extract 3 weight portions
Radix Ophiopogonis extract 1 weight portion.
7, as claim 1,2,3,4,5 or 6 described preparation of drug combination methods, it is characterized in that this method is:
The Radix Ginseng Rubra medical material is thinly sliced, and the ethanol that adds 40～100% (v/v) of 4～10 times of crude drug amounts carries out reflux 3～6 times, each half an hour; Merge extractive liquid,, decompression and solvent recovery; The concentrated solution that obtains is injected macroporous adsorptive resins, doubly measure the purified water eluting of column volume earlier with 4-10, reuse 5-12 doubly measures column volume 10-30% ethanol elution, discards eluent, uses the 50-90% ethanol elution then, collects the eluent that 4-8 doubly measures column volume; The eluent that obtains is concentrated, and drying is pulverized, and promptly gets Radix Ginseng Rubra extract; Get medical material Radix Ophiopogonis, pulverize, 50～100% the ethanol that adds 4～10 times of crude drug amounts carries out heating and refluxing extraction 1～4 time, each 0.5-2 hour; Merge extractive liquid,, decompression and solvent recovery; The concentrated solution that obtains is injected macroporous adsorptive resins, doubly measure the purified water eluting of column volume earlier with 2-6, reuse 2-6 doubly measures column volume 30-50% ethanol elution, discards eluent, uses the 70-90% ethanol elution then, collects the eluent that 1-6 doubly measures column volume; Concentrate, drying is pulverized, and promptly gets Radix Ophiopogonis extract; Get Radix Ginseng Rubra extract and Radix Ophiopogonis extract, add adjuvant, be prepared into the dosage form of clinical acceptance: tablet, capsule, pill, granule, transfusion, freeze-dried powder.
8, preparation of drug combination method as claimed in claim 7 is characterized in that this method is:
The Radix Ginseng Rubra medical material is thinly sliced, and 60% the ethanol that adds 6 times of crude drug amounts carries out reflux 4 times, each half an hour; Merge extractive liquid,, decompression and solvent recovery; The concentrated solution that obtains is injected macroporous adsorptive resins, and with the purified water eluting of 6 times of amount column volumes, 8 times of amounts of reuse column volume, 20% ethanol elution discards eluent, uses 70% ethanol elution then, collects the eluent of 8 times of amount column volumes earlier; With the eluent that obtains, reclaim ethanol and concentrated, vacuum drying is pulverized, and promptly gets Radix Ginseng Rubra extract; Get medical material Radix Ophiopogonis, pulverize, 80% the ethanol that adds 6 times of crude drug amounts carries out heating and refluxing extraction 2 times, each 1 hour; Merge extractive liquid,, decompression and solvent recovery; The concentrated solution that obtains is injected macroporous adsorptive resins, and with the purified water eluting of 4 times of amount column volumes, 4 times of amounts of reuse column volume, 40% ethanol elution discards eluent, uses 80% ethanol elution then, collects the eluent of 3 times of amount column volumes earlier; The eluent that obtains is concentrated, and vacuum drying is pulverized, and promptly gets Radix Ophiopogonis extract; Get Radix Ginseng Rubra extract and Radix Ophiopogonis extract, add adjuvant, be prepared into clinical acceptable forms: tablet, capsule, pill, granule, transfusion, freeze-dried powder.
9, as claim 1,2,3,4, the application of 5 or 6 described pharmaceutical compositions in the medicine of preparation anti-hemorrhagic shock, anti-cardiogenic shock or heart failure resistance.
10, pharmaceutical composition as claimed in claim 9 has the myocardial contraction of raising, reduces myocardial oxygen consumption, expands peripheral blood vessel, reduces Peripheral resistance, improves hypoxia-bearing capability, improves anti-fatigue ability, improves myocardial ischemia in preparation, reduce the content of aspartate aminotransferase, creatine phosphokinase or lactic acid dehydrogenase in the ischemic myocardium serum, suppress that systolic arterial pressure, auterial diastole are pressed, left indoor systolic pressure and ± decline of dP/dt or dwindle application in the medicine of myocardial infarction area effect.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100630878A CN100352480C (en) | 2005-04-06 | 2005-04-06 | Pharmaceutical composition, its preparation method and usage |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2005100630878A CN100352480C (en) | 2005-04-06 | 2005-04-06 | Pharmaceutical composition, its preparation method and usage |
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| CN1843455A true CN1843455A (en) | 2006-10-11 |
| CN100352480C CN100352480C (en) | 2007-12-05 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104623262A (en) * | 2013-11-12 | 2015-05-20 | 雅安三九药业有限公司 | Red ginseng and dwarf lilyturf tuber injection as well as preparation method thereof |
| CN106237065A (en) * | 2016-08-25 | 2016-12-21 | 神威药业集团有限公司 | A kind of pharmaceutical composition and preparation method thereof |
| CN106511745A (en) * | 2016-11-25 | 2017-03-22 | 神威药业集团有限公司 | Xuanmaiganju composition (composition consisting of radix scrophulariae, radix ophiopogonis, liquorice root and radix platycodonis) and preparation method of composition |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1596954A (en) * | 2004-09-24 | 2005-03-23 | 贵阳云岩西创药物科技开发有限公司 | Red ginseng and ophiopogon root preparation and its making method |
-
2005
- 2005-04-06 CN CNB2005100630878A patent/CN100352480C/en active Active
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104623262A (en) * | 2013-11-12 | 2015-05-20 | 雅安三九药业有限公司 | Red ginseng and dwarf lilyturf tuber injection as well as preparation method thereof |
| CN104623262B (en) * | 2013-11-12 | 2017-12-19 | 华润三九（雅安）药业有限公司 | A kind of Shenmai injection and preparation method thereof |
| CN106237065A (en) * | 2016-08-25 | 2016-12-21 | 神威药业集团有限公司 | A kind of pharmaceutical composition and preparation method thereof |
| CN106511745A (en) * | 2016-11-25 | 2017-03-22 | 神威药业集团有限公司 | Xuanmaiganju composition (composition consisting of radix scrophulariae, radix ophiopogonis, liquorice root and radix platycodonis) and preparation method of composition |
| CN106511745B (en) * | 2016-11-25 | 2020-06-16 | 神威药业集团有限公司 | Xuanmai Ganju composition and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN100352480C (en) | 2007-12-05 |
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