CN1296048C - Ginseng and ophiopogon saponin drops and their preparing method - Google Patents
Ginseng and ophiopogon saponin drops and their preparing method Download PDFInfo
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- CN1296048C CN1296048C CNB2003101217120A CN200310121712A CN1296048C CN 1296048 C CN1296048 C CN 1296048C CN B2003101217120 A CNB2003101217120 A CN B2003101217120A CN 200310121712 A CN200310121712 A CN 200310121712A CN 1296048 C CN1296048 C CN 1296048C
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Abstract
The present invention relates to a ginseng and ophiopogon total saponin drop pill preparation which is extracted from the traditional Chinese medicine of red ginseng and ophiopogon root and a preparation method thereof. The contents of the effective constituents of ginsenoside and ophiopogon saponin are largely improved, and bioavailability is obviously improved. The present invention can be used for preventing and treating cardiovascular and cerebrovascular diseases. The preparation technique is simple, and is suitable for commercial production.
Description
Technical field:
The present invention relates to total Saponin dropping pill formulation of Rhizoma Zingiberis Recens that a kind of effective site of extracting from Chinese medicine Radix Ginseng Rubra and Radix Ophiopogonis forms and preparation method thereof.
Background technology:
Ancient prescription ginseng winter drink comes from Ming Dynasty Qin Jing bright " disease is controlled because of arteries and veins ", is to be formed by the Chinese medicine equivalent prescription of distinguishing the flavor of Radix Ginseng, Radix Ophiopogonis two.Major function is a supplementing QI to prevent collapse, Yin-nourishing and body fluid promoting, and multiple arteries and veins nourishes heart; According to the red ginseng and ophiopogon root preparation of ancient prescription ginseng winter drink exploitation comprise that Rhizoma Zingiberis Recens granule, Rhizoma Zingiberis Recens loose, SHENMAI ZHUSHEYE etc.Confirm through pharmacological evaluation, SHENMAI ZHUSHEYE is to cardiovascular enhancing myocardial contraction that act as, increase cardiac output, the expansion peripheral blood vessel increases the blood confession of histoorgan, improves the Hypoxia and ischemia state of histoorgan, SHENMAI ZHUSHEYE also has the adjusting immunity function in addition, strengthening the body resistance improves the resistance of aged lung cardiaopath to infecting, and malignant tumor chemotherapy is had synergism and attenuation etc.But concerning the cardiovascular and cerebrovascular vessel patient, must take medicine for a long time, SHENMAI ZHUSHEYE is used inconvenience; Rhizoma Zingiberis Recens granule, Rhizoma Zingiberis Recens loose, and curative effect is limited, and dose is big.
The common preparation method of existing red ginseng and ophiopogon root preparation raw material is with Radix Ginseng and uses alcohol reflux Radix Ophiopogonis, and extracting solution is with remove impurity with active carbon or be not further purified again, promptly.The material effective component ginsenoside who obtains and Radix Ophiopogonis saponin content low, the impurity content height, the difficult relatively control of quality, the curative effect of medicine is affected, untoward reaction is also big.Patent CN1283500A " a kind of aseptic ' Shenmai ' powder for injection and preparation method thereof ", and CN1283499A " preparation method that a kind of freeze-dried ' Shenmai ' powder for injection is new ", adopt water to carry and add macroporous resin method, improved greatly the ginsenoside and Radix Ophiopogonis Saponin content, and be used for preparing injection Rhizoma Zingiberis Recens lyophilized formulations.But lyophilized formulations has the production cost height, and patient uses shortcomings such as inconvenience.
Summary of the invention:
The object of the present invention is to provide a kind of by Chinese medicine Radix Ginseng Rubra and Radix Ophiopogonis being the total Saponin dropping pill formulation of Rhizoma Zingiberis Recens that raw material is made.
Another object of the present invention is to provide a kind of by the total Saponin of making Radix Ginseng Rubra and Radix Ophiopogonis of Rhizoma Zingiberis Recens preparation method and be the preparation method of the dropping pill formulation made of active component with the total Saponin of the Rhizoma Zingiberis Recens that is extracted.
The total Saponin of active component Rhizoma Zingiberis Recens of dropping pill formulation of the present invention obtains by two kinds of methods: (1) Radix Ginseng Rubra and Radix Ophiopogonis respectively through extraction, chromatography, concentrate, drying steps is made ginsenoside's extract and Radix Ophiopogonis saponin extract, with ginsenoside's extract and Radix Ophiopogonis saponin extract be active component, mix with certain proportioning; Wherein ginsenoside's content even can reach more than 80% greater than 50% in ginsenoside's extract, in the Radix Ophiopogonis saponin extract Radix Ophiopogonis Saponin content greater than 50%.(2) with Radix Ginseng Rubra and Radix Ophiopogonis together by extraction, chromatography, concentrate, drying makes the ginsenoside and Radix Ophiopogonis the Saponin mixed extract; Wherein, the content of the total Saponin of Rhizoma Zingiberis Recens is greater than 50%.Then, be that pharmaceutical carrier is made dropping pill formulation again with the Polyethylene Glycol.
The preparation method of the total Saponin of Rhizoma Zingiberis Recens of the present invention is: (1) adopts alcohol extraction to Radix Ginseng Rubra, in conjunction with macroporous resin and extracting process, to adopting alcohol extraction and macroporous resin method Radix Ophiopogonis, the total Saponin finished product of the Rhizoma Zingiberis Recens that obtains impurity is few, the effective ingredient ginsenoside and Radix Ophiopogonis Saponin content respectively greater than 50%; (2) with Radix Ginseng Rubra with adopt alcohol extraction Radix Ophiopogonis simultaneously, in conjunction with the purification process of macroporous resin, the content of the total Saponin of Rhizoma Zingiberis Recens is greater than 50%.
The present invention adopts drops, makes the easier absorption of effective ingredient, and bioavailability is further enhanced, and side effect is also littler.
The preparation method (method A) of separately extracting Radix Ginseng Rubra of the present invention and Radix Ophiopogonis saponin component is as follows:
Leptoradix Ginseng Rubra is added about 8 times of amount 70% ethanol soaked overnight in the hot reflux extraction pot, heating and refluxing extraction 1.5 hours, emit medicinal liquid, medicinal residues add 8 times of amount 70% ethanol extractions 1.5 hours again, extract once, extracting solution concentrates and reclaims ethanol to there not being the alcohol flavor, put cold, on the HPD-100 type macroporous resin handled well, absorption is spent the night, with water towards post and do alpha-Naphthol, the concentrated sulphuric acid check, use instead when being negative 75% ethanol wash post and collect alcohol eluen to eluent near when colourless till, decompression recycling ethanol is not to there being the alcohol flavor, puts coldly, and it is closely colourless to be extracted to n-butanol layer with water-saturated n-butanol, merge butanol extraction liquid and be evaporated to dried, powder delivery, powder takes out standby in 60 ℃ of baking oven vacuum dryings 4～5 hours.
Add about 8 times of amount 75% ethanol soaked overnight in the hot reflux extraction pot Radix Ophiopogonis, heating and refluxing extraction 1.5 hours, emit medicinal liquid, medicinal residues add 8 times of amount 75% ethanol extractions 1.5 hours again, extract three times, extracting solution concentrate to reclaim ethanol to there not being the alcohol flavor, put cold, on the HPD-100 type macroporous resin handled well, absorption is spent the night, with water towards post and do α-Nai phenol, concentrated sulphuric acid check, use instead when being negative 75% ethanol wash post and collect alcohol eluen to eluent near when colourless till, with eluent peroxidating aluminum post, collected post liquid, decompression recycling ethanol is to doing, and powder delivery weighs up powder weight and calculates yield.
The preparation method (method B) of extracting Radix Ginseng Rubra of the present invention and Radix Ophiopogonis saponin component simultaneously is as follows:
Take by weighing Radix Ophiopogonis, Radix Ginseng Rubra two flavor medical materials, Radix Ginseng Rubra is given broken section as one thinks fit, adds 8 times of amount 70% alcohol heating reflux and extracts each 1.5 hours 3 times.Merge 3 times extracting solution, 80 ℃ of decompression recycling ethanols are to not having the alcohol flavor and making crude drug: medicinal liquid is about 1: 2, put cold, centrifugal, the HPD-100 type macroporous resin column of having handled well on the extracting centrifugal liquid, till being negative with water elution to alpha-Naphthol, concentrated sulphuric acid experiment, again with 70% ethanol elution of 4 times of column volumes and collect eluent, with eluent after 80 ℃ of concentrating under reduced pressure become the thick paste shape, 80 ℃ of drying under reduced pressure, pulverize, get Rhizoma Zingiberis Recens total glycosides Saponin powder.
The preparation method of the total Saponin drop pill of Rhizoma Zingiberis Recens of the present invention is: ginsenoside's extract that (1) makes said method A and Radix Ophiopogonis saponin extract and adjuvant polyethylene glycol 6000 (PEG6000), cross 60 mesh sieves respectively, mix with certain proportioning; (2) total saponin extract of said method B being made of Rhizoma Zingiberis Recens and adjuvant polyethylene glycol 6000 (PEG6000) are crossed 60 mesh sieves respectively, mix with certain proportioning; Then, said method (1) or (2) gained mixture are put 80 ℃ of-90 ℃ of heating in water bath, and be stirred to and be molten state, add the suitable quantity of water mixing, the impouring insulation is dripped in the system device.Select the water dropper of water dropper for use, splash in the methyl-silicone oil liquid coolant with the speed of 30 ± 5 of per minutes by the heavy 45mg of every ball.
With the dropping pill formulation of the present invention that said method (1) makes, the weight proportion of Radix Ginseng Rubra extract ginsenoside, Radix Ophiopogonis extract Saponin Radix Ophiopogonis and polyethylene glycol 6000 is 5-10: 1-3: 40-80, is preferably 6-8: 2-3: 50-70 most preferably is 3: 1: 20.With the dropping pill formulation of the present invention that said method (2) makes, the weight proportion of total saponin extract of Rhizoma Zingiberis Recens and polyethylene glycol 6000 is 1-10: 10-25, is preferably 3-7: 15-20 most preferably is 1: 5.
Pharmaceutical dosage form of the present invention is a drop pill, and it is shaped as reddish brown-brownish black round bead shape, and size evenly.
The heavy scope 20～60mg of described drop pill ball, weight differential ± 15%.
The invention has the advantages that, Radix Ginseng Rubra and Radix Ophiopogonis have the purity height through the extract itself that method of the present invention obtains, stability is strong, and quality is good, good effect, the characteristics of few side effects, be made into drop pill again,, avoid first pass effect through sublingual administration, the bioavailability height, effective ingredient absorbs directly into blood and reaches quick-acting purposes through the oral cavity mucosa; Owing to utilize modern special extraction process and high-tech Quality Control means, improve content of effective and quality control standard, really guarantee the safety and the effectiveness of medicine.
The test of pesticide effectiveness that the total Saponin drop pill of the Rhizoma Zingiberis Recens raw material (hereinafter to be referred as the total Saponin of Rhizoma Zingiberis Recens) of gained of most preferably filling a prescription according to the present invention below carries out is described further.
1, test material
1.1 main medicine and reagent
The total Saponin raw material of Rhizoma Zingiberis Recens is provided by Jiangsu Zhengda Tianqing Drug Industry Co., Ltd, and lot number 030227, content are 50g crude drug/g raw material, faces with preceding usefulness 0.9% sodium chloride injection to be made into desired concn; Nitroglycerin injection, 5mg/1ml is provided by Mingxing Pharmaceutical Factory, Guangzhou, lot number 020903.Chlorination nitro blue tetrazolium (NBT): olive drab(O powder crystallization, the Shanghai chemical chemical reagent work product that advances, lot number: 20010801.
1.2 experimental animal: the SD rat is provided by Jiangsu Province's Experimental Animal Center, quality certification book number: SCXK (Soviet Union) 2002-0031; The hybrid dog, body weight 8-10.5kg is provided by animal reproduction field, Xian Tangshan Green Dragon mountain, Jiangning, quality certification book number: SCXK (Soviet Union) 2002-0018.
1.3 key instrument: polygraph, Japanese photoelectricity RM-6000 type; Electromagnetic blood flowmeter, Japanese photoelectricity FVM-1200 type and FB-130 Electromagnetic Flow probe are used for measuring cardiac output; Electromagnetic blood flowmeter, Japanese photoelectricity FVM-3100 type and FI-015 Electromagnetic Flow probe are used for measuring coronary artery blood flow; The animal artificial respirator, the DH-101 type.
20.3 experimental condition: before and after the administration, the experimental rat sub-cage rearing is fed full-valence pellet feed, freely drinks water, and room temperature 20-25 ℃, relative humidity 65-70%.
2 statistical method
The statistical analysis of testing data adopts the t check relatively of two sample means, two sample rates X relatively
2Check.
3 test methods and result
3.1 the total Saponin of Rhizoma Zingiberis Recens is to the influence of anesthetized dog heart coronary artery ligation myocardial infarction and ischemia model
Get 30 of hybrid dogs, be divided into 5 groups at random, 6 every group, male and female half and half.With 3% pentobarbital sodium 1ml/kgi.v anesthesia, cervical region and groin cut, and separate trachea, femoral artery and femoral vein.The former connects artificial respirator at intubate, and the artificial respiration uses.Latter's intubate respectively connects pressure transducer for measuring blood pressure and transfusion, administrable; The IV intercostal is opened breast, excises the IV rib, vertically cuts off pericardium along phrenic nerves, makees the pericardium cradle; Separate aorta, hang up the Electromagnetic Flow probe, probe connects electromagnetic blood flowmeter, measures cardiac output; Separate that to fall branch before the coronary artery last 1/3, hang up Electromagnetic Flow probe mensuration coronary circulation blood flow; Do left ventricular cannulation through the apex of the heart, connect the determination of pressure sensor left ventricular pressure, this signal is handled through direct current amplifier and differentiator, can get the left ventricular diastolic end and press and the pressure differential map, and the former reflects the diastole situation of heart, the contractility of latter's reflecting myocardium; Before coronary artery, fall below branch first main split or before and branch 1/2 place falls, and 1/3 place (falling the traffic branch of branch before the blocking-up) penetrates silk thread with sewing needle under left-handed branch second branch, it is standby that each makes a call to an empty knot, for blocking-up arteria coronaria usefulness; Extremity connect ECG electrode, measure the II lead electrocardiogram; Infuse (10/min), keeping the full and water-electrolyte balance of circulation, and supplying intravenously administrable to use with 0.9% sodium chloride injection through femoral vein.
After more than operation is finished, the gauze flap coverage, normal saline is preserved moisture, observe These parameters, when fluctuating less than 10% and keeping more than the 30min, duodenum gives the total Saponin 0.4,0.8 of Rhizoma Zingiberis Recens, 1.6g crude drug/Kg respectively then, and the administration volume is 1ml/Kg, the model control group duodenum gives isometric NS, positive controls intravenous injection isometric(al) nitroglycerin 0.25mg/Kg.Observed 4 hours continuously, relatively the situation of change of each time point and the preceding every index of administration after the administration.
Influence to ECG
ECG shows as ischemic ECG immediately behind the coronary ligation, mainly shows as the S-T skew, and the T wave height is alarmmed, and premature beat appears in the minority animal.Duodenum gives in the total Saponin of Rhizoma Zingiberis Recens, heavy dose ofly all can significantly improve the S-T skew that causes because of myocardial ischemia, and onset time is 60min after administration, and effect can be maintained until after the administration 4 hours, the results are shown in Table 1.
Table 1 pair coronary ligation cause myocardial ischemia dog ECG S-T influence (X ± SD, %)
| Group | Heavy dose of group | Middle dosage group | Small dose group | Positive controls | Model control group |
| 5min 10min 15min 20min 30min 60min 90min 120min 150min 180min 210min 240min | 0.37±60.56 12.65±58.72 58.62±88.82 21.80±102.38 12.12±58.79 -46.67±5.77 * -58.89±8.369 -72.12±10.50 -87.25±6.58 * -89.10±7.92 * -95.77±3.75 * -97.62±4.12 * | 25.09±33.05 34.42±42.43 9.35±32.45 -18.09±23.74 -6.62±37.82 0.38±48.53 -32.48±36.15 * -63.60±15.76 * -90.11±7.31 ** -93.14±7.31 ** -95.52±4.55 ** -98.55±2.51 ** | 16.31±24.34 25.17±19.82 12.43±34.89 23.84±30.59 31.12±34.02 25.26±41.43 11.75±36.29 20.75±46.41 25.33±29.83 20.32±28.95 30.36±41.03 19.76±32.17 | 19.60±19.75 0.29±22.48 -21.23±21.52 -19.24±19.13 -34.60±17.83 -37.34±12.71 -52.84±9.75 * -72.32±7.24 * -93.67±5.57 * -97.49±2.80 * -98.47±2.38 * -98.47±2.38 * | 14.63±21.64 26.57±29.78 27.64±38.94 35.18±35.90 39.11±44.80 35.82±51.14 41.87±46.69 50.47±56.74 55.63±39.18 30.94±35.89 50.83±46.23 59.37±63.77 |
Compare with model control group,
*P＜0.05,
*P＜0.01.
Influence to heart blood-pumping function
Duodenum gives in the total Saponin of Rhizoma Zingiberis Recens, the heavy dose of cardiac output of Ischemic Heart, every rich output of all can obviously increasing, and improves cardiac index, and onset time is 90min after administration, can be maintained until 150min after the administration approximately, illustrates that it can improve cardiac pumping function.The results are shown in Table 2-4.
Table 2 pair coronary ligation cause the kinemic influence of myocardial ischemia dog (X ± SD, %)
| Group | Heavy dose of group | Middle dosage group | Small dose group | Positive controls | Model control group |
| 0min 5min 10min 15min 20min 30min 60min 90min 120min 150min 180min 210min 240min | -3.88±5.62 -1.23±2.09 -3.25±6.01 -6.45±9.13 -7.78±11.28 -11.19±11.44 -9.99±7.10 -11.94±6.79 -13.92±4.06 ** -21.92±12.92 * -33.54±24.79 -44.07±34.18 -47.98±35.20 | -1.64±8.31 -1.24±3.52 -5.35±3.82 -10.98±7.18 -13.14±9.46 -16.24±11.89 -12.87±6.08 -10.49±3.97 * -15.75±3.47 ** -39.11±19.37 -49.72±22.43 -63.99±33.50 -71.93±38.96 | -3.93±10.35 -1.46±9.35 -1.47±12.32 -3.95±11.49 -4.09±18.45 -17.55±26.32 -10.25±18.49 -22.96±27.56 -37.84±20.44 -44.02±13.69 -49.08±20.53 -41.69±12.78 -54.38±14.91 | 8.52±11.26 -2.82±4.13 -1.75±7.25 -4.15±7.95 -6.81±9.17 -11.11±14.30 -17.37±15.73 -26.93±4.79 -30.31±16.15 * -38.81±14.12 * -44.34±8.40 * -50.69±7.11 -50.84±3.75 * | -5.13±11.73 5.16±7.73 3.42±10.22 5.29±10.54 -14.99±28.24 -37.58±46.02 -30.55±28.29 -52.90±29.79 -58.01±17.39 -64.02±19.60 -69.88±22.33 -71.65±22.97 -74.08±24.69 |
Compare with model control group,
*P＜0.05,
*P＜0.01.
Table 3 pair coronary ligation cause the whenever rich output of myocardial ischemia dog influence (X ± SD, %)
| Group | Heavy dose of group | Middle dosage group | Small dose group | Positive controls | Model control group |
| 0min 5min 10min 15min 20min 30min 60min 90min 120min 150min 180min 210min 240min | -0.43±3.56 0.77±2.76 1.14±8.74 -0.82±12.18 10.25±32.23 -6.55±12.37 49.06±78.21 13.63±29.50 * -0.43±14.83 ** -4.03±27.46 ** -16.28±39.75 * -22.85±52.98 -25.48±55.20 | 4.12±6.64 -0.99±3.62 -4.40±2.37 -5.94±11.71 -10.08±7.49 -14.60±11.08 0.79±13.28 -3.84±8.99 * -10.01±13.30 ** -32.12±33.48 -40.03±40.42 -53.64±52.37 -61.01±58.44 | -1.62±9.16 5.03±7.59 -1.65±11.13 -5.95±9.58 -2.74±14.24 -15.48±21.47 -1.88±30.62 -18.52±16.85 -5.46±10.23 -29.35±21.92 -26.88±12.53 -38.79±25.13 -46.82±20.85 | 4.63±13.26 -2.92±3.94 * -1.52±7.27 -4.64±7.93 -8.78±9.68 -9.65±17.15 -5.02±39.72 -25.11±6.55 -11.49±33.96 * -26.18±23.89 * -25.04± -35.06±23.75 * -32.16±17.61 * | -6.56±6.56 7.92±9.39 6.60±10.33 -1.19±7.10 -12.34±24.94 -35.40±41.34 -11.48±40.53 -48.32±26.78 -52.45±12.99 -59.59±18.19 -66.58±22.23 -68.73±23.55 -41.38±25.38 |
Compare with model control group,
*P＜0.05,
*P＜0.01.
Table 4 pair coronary ligation cause myocardial ischemia dog cardiac index influence (X ± SD, %)
| Group | Heavy dose of group | Middle dosage group | Small dose group | Positive controls | Model control group |
| 0min 5min 10min 15min 20min 30min 60min 90min 120min 150min 180min 210min 240min | -3.88±5.62 -1.23±2.09 -3.25±6.01 -6.45±9.13 -7.78±11.28 -11.19±11.44 -9.99±7.10 -11.94±6.79 -13.92±4.06 ** -21.22±12.92 * -33.54±24.79 -44.07±34.18 -47.98±35.20 | -1.64±8.31 -1.24±3.52 -5.35±3.82 -10.98±7.18 -13.14±9.46 -16.24±11.89 -12.87±6.08 -10.49±3.97 * -15.75±3.47 ** -39.11±19.37 -49.72±22.43 -63.99±33.50 -71.93±38.96 | -6.33±10.34 -5.64±8.32 -4.41±12.02 -7.99±11.43 -11.09±18.46 -17.82±26.29 -20.75±18139 -22.47±20.92 -28.14±27.33 -40.25±29.14 -59.81±20.31 -51.52±29.25 -64.85±20.19 | 8.52±11.26 -2.82±4.13 * -1.75±7.25 -4.15±7.95 -6.81±9.17 -11.11±14.30 -17.37±15.73 -30.46±26.93 -22.97±30.31 * -38.81±14.12 * -44.34±8.40 * -50.69±7.11 -50.84±3.75 * | -5.13±11.73 5.16±7.73 3.42±10.22 -5.29±10.54 -14.99±28.24 -37.58±46.02 -30.55±28.29 -52.90±29.79 -58.01±17.39 -64.02±19.60 -69.88±22.33 -71.65±22.97 -74.08±24.69 |
Compare with model control group,
*P＜0.05,
*P＜0.01.
Variation to coronary flow in the experiment:
Duodenum gives the total Saponin heavy dose of Rhizoma Zingiberis Recens can obviously increase coronary flow, and onset time is 90min after administration, can be maintained until 150min after the approximately administration, illustrates that it can improve the blood supply of Ischemic Heart.The results are shown in Table 5.
Table 5 pair coronary ligation cause myocardial ischemia dog coronary flow influence (X ± SD, %)
| Group | Heavy dose of group | Middle dosage group | Small dose group | Positive controls | Model control group |
| 0min 5min 10min 15min 20min 30min 60min 90min 120min 150min 180min 210min 240min | 2.52±16.01 -0.55±4.15 -4.65±11.76 -5.38±11.25 -7.60±11.27 -9.53±11.14 -9.63±13.51 -14.97±17.73 ** -14.23±16.63 * -13.55±16.02 * -22.49±22.04 -26.24±17.11 -34.37±14.46 | 10.78±23.01 -4.20±7.53 -7.42±12.42 -15.75±13.53 -15.72±11.66 -21.19±16.76 -16.68±15.24 -23.02±13.00 ** -19.34±12.77 -26.52±22.55 -35.27±17.76 -41.18±19.29 -39.16±9.20 | 9.09±17.14 -5.31±10.35 -1.66±15.91 -10.52±16.29 -12.75±21.38 -26.14±14.22 -22.85±29.18 -34.59±14.65 -25.93±18.38 -30.27±5.90 -31.24±18.32 -30.26±18.07 -33.48±12.35 | 7.51±29.44 17.00±24.79 30.49±26.27 ** 22.64±15.94 ** 39.35±52.79 * 18.06±22.77 ** 3.08±21.15 * 5.16±28.24 ** -1.41±27.25 * 8.83±23.46 ** 3.50±21.99 ** -2.64±21.17 ** -23.49±39.53 | 4.99±27.71 -8.61±17.23 -11.16±14.51 -19.45±18.62 -19.05±18.18 -36.91±24.72 -32.28±19.98 -44.50±4.46 -35.29±10.08 -38.12±6.10 -41.94±8.93 -40.12±8.57 -43.74±13.22 |
Compare with model control group,
*P＜0.05,
*P＜0.01.
More than experiment and other experimental results show, duodenum gives to fall the ischemic electrocardiogram that a myocardial infarction and ischemia model causes before each dosage group of the total Saponin of Rhizoma Zingiberis Recens all can be improved dog ligation coronary artery to some extent, myocardial contractility and cardiac pumping function reduction are also had some improvement, heart acting and myocardial oxygen consumption are maintained than reasonable levels, can significantly increase simultaneously the blood flow of arteria coronaria, and total peripheral resistance, heart rate and blood pressure etc. are not all had significantly effect.The total Saponin of prompting Rhizoma Zingiberis Recens has excellent curative to myocardial ischemia.
3.2 the total Saponin of Rhizoma Zingiberis Recens is to the influence of coronary ligation rat acute myocardial infarction
Get 84 of SD rats, body weight 180-220g is divided into 6 groups at random: blank group, model control group, positive controls, the high, medium and low dosage group of the total Saponin of Rhizoma Zingiberis Recens, 14 every group, male and female half and half.Irritate stomach respectively and give the total Saponin 1.25,2.5 of Rhizoma Zingiberis Recens, 5g/Kg/ time, positive controls lumbar injection nitroglycerin injection 0.8mg/Kg/ time, blank group and model control group are irritated stomach and are given isometric(al) NS, administration every day 2 times, continuous 4 days.After administration in second day, except that the blank group, each group row left coronary artery ligation causes the rat acute myocardial infarction; 1h after the administration in the 4th day, when being rat coronary ligation 48h, the intraperitoneal anesthesia of 40mg/kg pentobarbital sodium, vena femoralis injection 100U/100g heparin whole body heparinization detects hemorheological indexes such as whole blood viscosity, packed cell volume again through common carotid artery blood-letting 4-5ml then; Getting blood finishes, take out heart, keep ventricle, wash away blood with normal saline, do to be parallel to the ventricle section of the thick 0.2mm of coronary sulcus, immerse 0.1% nitro tetrazole orchid (N-BT), 370C jolting dyeing 10 minutes, accurately weigh in clip dyeing district and non-dyeing district ventricle, calculate the infarct ventricle and account for full chamber percentage by weight.Result of the test sees Table 8,9.
The influence of table 8 pair rat acute myocardial infarct size (X ± SD)
| Group | Number of animals (individual) | The infarcted region ventricle weighs/full chamber heavy (%) |
| Dosage group TQG-6 small dose group among the heavy dose of group of the blank group model matched group positive controls TQG-6 TQG-6 | 14 10 8 10 9 10 | 0 30.8±1.7 25.8±6.2 * 26.1±5.0 * 28.1±6.0 28.5±4.3 |
Compare with model control group,
*P＜0.05.
The influence of table 9 pair acute coronary ligation hemorheology of rat (X ± SD)
| Group | Blank | The model contrast | Positive control | Heavy dose of | Middle dosage | Low dose of |
| In cut the low erythrocyte aggregation index packed cell volume of cutting | 7.51±0.83 14.38±2.23 2.41±0.21 42.5±2.2 | 8.52±1.02 * 16.84±2.32 * 2.53±0.14 44.7±3.3 | 8.43±0.65 * 16.09±1.21 2.40±0.23 42.2±3.7 | 7.73±0.61 13.80±1.69 ** 2.30±0.11 ** 43.9±2.7 | 7.18±1.13 * 13.05±2.51 ** 2.23±0.16 ** 40.6±5.2 | 7.49±1.41 13.41±3.35 * 2.17±0.24 ** 43.3±4.4 |
Compare with the blank group,
*P＜0.05; With model control group quite,
*P＜0.05,
*P＜0.01
Result of the test shows that the heavy dose of group of the total Saponin of Rhizoma Zingiberis Recens can reduce the infarct size of rats with acute myocardial infarction, and each dosage group all can reduce blood viscosity simultaneously, reduces erythrocyte aggregation, improves blood circulation, has certain function of resisting myocardial ischemia.
The specific embodiment:
Further specify the present invention by the following examples, embodiment only is used to illustrate the present invention, rather than limits the present invention by any way.
Embodiment 1:
Get Leptoradix Ginseng Rubra 100g, add 800ml 70% ethanol soaked overnight in the hot reflux extraction pot, heating and refluxing extraction 1.5 hours, emit medicinal liquid, medicinal residues add 800ml 70% ethanol extraction 1.5 hours again, extract once, extracting solution concentrates and reclaims ethanol to there not being the alcohol flavor, puts cold, on the HPD-100 type macroporous resin handled well, absorption is spent the night, with water towards post and do α-Nai phenol, concentrated sulphuric acid check, use instead when being negative 75% ethanol wash post and collect alcohol eluen to eluent near when colourless till, decompression recycling ethanol is to there not being the alcohol flavor, put coldly, it is closely colourless to be extracted to n-butanol layer with water-saturated n-butanol, merges butanol extraction liquid and also is evaporated to dried, powder delivery, powder can get 4.7g ginsenoside extract in 60 ℃ of baking oven vacuum dryings 4～5 hours, and wherein ginsenoside's content can reach 88%.
Embodiment 2:
Get 100g Radix Ophiopogonis, add about 800ml 75% ethanol soaked overnight in the hot reflux extraction pot, heating and refluxing extraction 1.5 hours, emit medicinal liquid, medicinal residues add 800ml 75% ethanol extraction 1.5 hours again, extract three times, extracting solution concentrates and reclaims ethanol to there not being the alcohol flavor, put cold, on the HPD-100 type macroporous resin handled well, absorption is spent the night, with water towards post and do α-Nai phenol, the concentrated sulphuric acid check, use instead when being negative 75% ethanol wash post and collect alcohol eluen to eluent near when colourless till, with eluent peroxidating aluminum post, collected post liquid, decompression recycling ethanol is to doing, powder delivery can get 1.4g saponin extract Radix Ophiopogonis, wherein Radix Ophiopogonis Saponin content can reach 60%.
Embodiment 3:
Take by weighing Radix Ophiopogonis, Radix Ginseng Rubra two flavor medical material 200g and 100g respectively, Radix Ginseng Rubra is cut into chunks, and adds 2400ml 70% alcohol heating reflux and extracts each 1.5 hours 3 times.Merge 3 times extracting solution, 80 ℃ of decompression recycling ethanols are to not having the alcohol flavor and making crude drug: medicinal liquid is about 1: 2, puts cold, centrifugal, the HPD-100 type macroporous resin column of having handled well on the extracting centrifugal liquid, till being negative with water elution to alpha-Naphthol, concentrated sulphuric acid experiment, again with 70% ethanol elution of 4 times of column volumes and collect eluent, with eluent after 80 ℃ of concentrating under reduced pressure become the thick paste shape, 80 ℃ of drying under reduced pressure, pulverize, get the total Saponin powder of Rhizoma Zingiberis Recens 8.4g, wherein the content of the total Saponin of Rhizoma Zingiberis Recens reaches 60%.
Embodiment 4:
Take by weighing respectively Radix Ginseng Rubra and Radix Ophiopogonis the extract ginsenoside and Radix Ophiopogonis Saponin 5g and 1g, PEG6000 40g, cross 60 mesh sieves respectively, put 80 ℃ of heating in water bath, and be stirred to and be molten state, add 14ml water mixing, the impouring insulation is dripped in the system device.Select the water dropper of water dropper for use, splash in the methyl-silicone oil liquid coolant, drip and make ball with the speed of 30 of per minutes by the heavy 20mg of every ball, oil removing, drying, promptly.
Embodiment 5:
Take by weighing respectively Radix Ginseng Rubra and Radix Ophiopogonis the extract ginsenoside and Radix Ophiopogonis Saponin 10g and 3g, PEG6000 80g crosses 60 mesh sieves respectively, puts 85 ℃ of heating in water bath, and is stirred to and is molten state, adds 28ml water mixing, the impouring insulation is dripped in the system device.Select the water dropper of water dropper for use, splash in the methyl-silicone oil liquid coolant, drip and make ball with the speed of 35 of per minutes by the heavy 60mg of every ball, oil removing, drying, promptly.
Embodiment 6:
Take by weighing respectively Radix Ginseng Rubra and Radix Ophiopogonis the extract ginsenoside and Radix Ophiopogonis each 9g of Saponin and 3g, PEG6000 60g, cross 60 mesh sieves respectively, put 90 ℃ of heating in water bath, and be stirred to and be molten state, add 22ml water mixing, the impouring insulation is dripped in the system device.Select the water dropper of water dropper for use, splash in the methyl-silicone oil liquid coolant, drip and make ball with the speed of 30 of per minutes by the heavy 45mg of every ball, oil removing, drying, promptly.
Embodiment 7:
Take by weighing the total Saponin 10g of Rhizoma Zingiberis Recens, PEG6000 100g, cross 60 mesh sieves respectively, put 90 ℃ of heating in water bath, and be stirred to and be molten state, add 33ml water mixing, the impouring insulation is dripped in the system device.Select the water dropper of water dropper for use, splash in the methyl-silicone oil liquid coolant, drip and make ball with the speed of 30 of per minutes by the heavy 20mg of every ball, oil removing, drying, promptly.
Embodiment 8:
Take by weighing the total Saponin 10g of Rhizoma Zingiberis Recens, PEG6000 50g, cross 60 mesh sieves respectively, put 90 ℃ of heating in water bath, and be stirred to and be molten state, add 18ml water mixing, the impouring insulation is dripped in the system device.Select the water dropper of water dropper for use, splash in the methyl-silicone oil liquid coolant, drip and make ball with the speed of 30 of per minutes by the heavy 45mg of every ball, oil removing, drying, promptly.
Embodiment 9:
Take by weighing the total Saponin 10g of Rhizoma Zingiberis Recens, PEG6000 20g, cross 60 mesh sieves respectively, put 90 ℃ of heating in water bath, and be stirred to and be molten state, add 9ml water mixing, the impouring insulation is dripped in the system device.Select the water dropper of water dropper for use, splash in the methyl-silicone oil liquid coolant, drip and make ball with the speed of 35 of per minutes by the heavy 60mg of every ball, oil removing, drying, promptly.
Claims (4)
1, a kind of drop pill for the treatment of cardiovascular and cerebrovascular disease, it is characterized in that active component be the Radix Ginseng Rubra saponin extract and Radix Ophiopogonis saponin extract, wherein content of ginsenoside is greater than 80% in the Radix Ginseng Rubra saponin extract, and saponin content is greater than 50% Radix Ophiopogonis in the Radix Ophiopogonis saponin extract.
2, drop pill according to claim 1 is characterized in that content of ginsenoside in the Radix Ginseng Rubra extract 〉=88%, in the Radix Ophiopogonis extract Radix Ophiopogonis saponin content 〉=60%.
3,, it is characterized in that polyethylene glycol 6000 is a pharmaceutical carrier according to the dropping pill formulation of claim 1 or 2.
4, according to the drop pill of claim 3, it is characterized in that ginsenoside's extract, Radix Ophiopogonis saponin extract and the weight proportion of polyethylene glycol 6000 be 5-10: 1-3: 40-80.
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| CN100486630C (en) * | 2005-05-27 | 2009-05-13 | 成都迪康药物研究所 | Medicine composition for treating eye disease, and its use |
| CN101744989B (en) * | 2008-12-05 | 2014-01-29 | 天津天士力之骄药业有限公司 | Method for extracting schisandra chinensis, ginseng and dwarf lilyturf root and preparation thereof |
| KR101593618B1 (en) | 2009-05-26 | 2016-02-15 | (주)아모레퍼시픽 | Composition for improving bioavailability of saponin |
| CN102127212B (en) * | 2010-12-10 | 2013-11-06 | 中国电器科学研究院 | Terminal carboxyl group polyester resin for weather-resistance high-gloss powder coating and preparation method thereof |
| CN103131535B (en) * | 2011-11-29 | 2015-01-21 | 福建中烟工业有限责任公司 | Preparation method of ophoipogon japonicus extract and application thereof in cigarettes |
| CN106589048B (en) * | 2016-12-28 | 2019-03-22 | 华宝香精股份有限公司 | A kind of extracting method for the ophiopogon saponin improving antioxidant activity |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US4684628A (en) * | 1985-05-03 | 1987-08-04 | Yaguang Liu | Pharmaceutical composition containing pure San-Mai-Sen |
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