CN1679698A - Medicinal preparation containing notoginseng and lovge rhizome for treating cardio-cerebral blood vessel diseases and its preparing method - Google Patents
Medicinal preparation containing notoginseng and lovge rhizome for treating cardio-cerebral blood vessel diseases and its preparing method Download PDFInfo
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- CN1679698A CN1679698A CN 200510004925 CN200510004925A CN1679698A CN 1679698 A CN1679698 A CN 1679698A CN 200510004925 CN200510004925 CN 200510004925 CN 200510004925 A CN200510004925 A CN 200510004925A CN 1679698 A CN1679698 A CN 1679698A
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- rhizoma chuanxiong
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- RQKFOGXUTRDQPB-UHFFFAOYSA-N hydron;2,3,5,6-tetramethylpyrazine;chloride Chemical compound Cl.CC1=NC(C)=C(C)N=C1C RQKFOGXUTRDQPB-UHFFFAOYSA-N 0.000 description 1
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- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
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- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
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- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
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- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
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- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
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- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- ZAVXXBAIPSQJGS-UHFFFAOYSA-B tetracalcium;tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O.[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O.[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ZAVXXBAIPSQJGS-UHFFFAOYSA-B 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
A Chinese medicine for treating cerebrovascular and cerebrovascular diseases is prepared from notoginseng and Chuan-xiong rhizome through extracting.
Description
Technical field:
The present invention relates to a kind of pharmaceutical preparation for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof, said preparation is formed through extracting processing and preparing by Chinese medicine Radix Notoginseng, Rhizoma Chuanxiong.
Background technology:
Cardiovascular and cerebrovascular disease as coronary heart disease, cerebral infarction, is human disease and main causes of death, accounts for 1/3rd of general mortality rate, has surpassed cancer at its mortality rate of China.And along with the raising of China along with living standards of the people, the crowd who suffers from cardiovascular and cerebrovascular disease is huge day by day, leave invalid among the survivor, cause huge life to threaten to the patient, the patient needs to take medicine for a long time or all the life more simultaneously, quality of life is had a strong impact on, and causes white elephant also for patient family and even entire society.
At present, the Chinese medicine and western medicine of treatment coronary heart disease is a lot, but how many Western medicine has some side effect, and is not almost having effective method aspect the treatment of cerebrovascular disease.Chinese medicine has certain characteristic aspect the treatment cardiovascular and cerebrovascular disease, utilizes activating blood circulation to dissipate blood stasis method treatment cardiovascular and cerebrovascular disease that certain effect has been arranged, and becomes the focus of cardiovascular and cerebrovascular disease area research in recent years.
The invention provides a kind of Chinese prescription for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof, form, extract pharmaceutically active substance, press pharmaceutical dosage form and add adjuvant, make preparation with the galenic pharmacy routine techniques by Radix Notoginseng and Rhizoma Chuanxiong.Radix Notoginseng has removing stasis to stop bleeding, the function of the analgesic therapy of invigorating blood circulation.Cardiovascular and cerebrovascular disease mostly is deficiency in origin and excess in superficiality, the card of blood stasis due to qi deficiency.Therefore, if emphasize blood circulation promoting and blood stasis dispelling in the treatment simply, then can injure the human righteousness, it is empty to increase the weight of losing of healthy energy, and clinical can the appearance such as the curative effect instability, electrocardiogram improvement rate is lower, takes for a long time and causes nervous phenomenon such as breathe hard.And the pseudo-ginseng blood-circulation-invigovating blood stasis dispelling has the characteristics of " blood stasis dispelling is not just hindered ", simultaneously the strong effect of tonify deficiency is arranged again, can take into account the human righteousness in blood circulation promoting and blood stasis dispelling, so very suitable the use.Modern pharmacological research proves, Radix Notoginseng has tangible blood vessel dilating effect, can coronary artery dilator, cerebrovascular and peripheral blood vessel, increase coronary flow and cerebral blood flow, improve cerebral circulation, can also reduce myocardial oxygen consumption, reduce myocardial contraction, strengthen the hypoxia-bearing capability of heart and brain tissues, obviously to resisting myocardial ischemia and cerebral ischemia-reperfusion injury; Radix Notoginseng also has effects such as blood fat reducing, anti peroxidation of lipid, removing oxygen-derived free radicals, anticoagulant and thrombosis.The active component of Radix Notoginseng is that Radix Notoginseng total arasaponins is (referring to Yang Yun; Zhang Jing; the Chen Yuting chief editor; Natural Medicine Chemistry component extraction separation handbook (revised edition), Beijing: China Traditional Chinese Medicine Publishing House, 2003; second edition; 17 pages), the main component of the XUESHUANTONG ZHUSHEYE of list marketing, XUESAITONG ZHUSHEYE is exactly a Radix Notoginseng total arasaponins, and Radix Notoginseng is to the protective effect and the Radix Notoginseng total arasaponins blocking-up Ca of cardiac-cerebral ischemia hypoxic damage
2+The effect of passage is closely related.The main component of the XUESHUANTONG ZHUSHEYE of list marketing, XUESAITONG ZHUSHEYE is exactly a Radix Notoginseng total arasaponins, and clinical to be used for the treatment of cardiovascular and cerebrovascular disease respond well, no obvious adverse reaction.Drug use Rhizoma Chuanxiong of the present invention and Radix Notoginseng compatibility use.Rhizoma Chuanxiong has blood-activating and qi-promoting, and the function of wind-expelling pain-stopping is gone into pericardium channel, the title of " gas medicine in the blood " is arranged, have the characteristics of orderly and clearly mechanism of qi in blood circulation promoting and blood stasis dispelling, be apt to control stagnation of QI and blood and demonstrate,prove bitterly, can reach blood stasis with the Radix Notoginseng compatibility, the effect that mechanism of qi is smooth helps the treatment of cardiovascular and cerebrovascular disease.The main active of Rhizoma Chuanxiong is a ligustrazine.Ligustrazine (TMP) has the vascular smooth muscle of inhibition spasm, coronary artery dilating, coronary flow reduces the ischemic myocardial cells apoptosis, alleviates histopathology and changes, the effect that improves acute myocardial ischemia is arranged, and the rat myocardial ischemia and reperfusion arrhythmia is had good preventive and therapeutic effect.Its mechanism and blocking-up endothelin receptor, protecting myocardial cell film Ca
2+-ATP enzyme and Na
+-K
+-atpase activities etc. are relevant.Ligustrazine has the cerebral blood flow increasing amount, improve microcirculation in the brain, improve the hypoxia-bearing capability of cerebral tissue, plays the effect of protection cerebral ischemia, its mechanism and blocking-up Ca
2+, protection blood brain barrier, rising ischemia brain mitochondria film effects such as flowability, anti peroxidation of lipid relevant.TMP energy anticoagulant, reduction biologically active pdgf, its anti-aggregation is to have replaced the Ca on the platelet membrane
2+Reason.Secretion and mRNA thereof that TMP can also suppress the vascular endothelial cell plasminogen activator inhibitor (PAI-1) that the endotoxin lipopolysaccharide causes express, and the mRNA expression of inhibition vascular endothelial cell PAI-1 foundation level, this may be one of TMP treatment cardiovascular disease mechanism.TMP energy cholesterol reducing and fat, thus blood viscosity reduced, hypercholesterolemia and hypertriglyceridemia there are therapeutical effect.The ligustrazine preparation that has gone on the market has ligustrazine hydrochloride liquid drugs injection, powder pin and infusion solutions etc.Drug use Radix Notoginseng of the present invention and Rhizoma Chuanxiong compatibility compare with the above-mentioned preparation that has gone on the market, have increased active constituents of medicine; In addition, the mechanism of action of Radix Notoginseng total arasaponins, ligustrazine is also inequality, and both compatibilities use has increased action target spot and approach, has strengthened curative effect.
Summary of the invention:
The invention provides a kind of pharmaceutical preparation, said preparation is that feedstock production forms with Chinese medicine Radix Notoginseng and Rhizoma Chuanxiong, pharmaceutical preparation of the present invention, contain the pseudo-ginseng activity composition of effective dose and the Rhizoma Chuanxiong active component of effective dose, the pseudo-ginseng activity composition is made with Radix Notoginseng, and the Rhizoma Chuanxiong active component is made with Rhizoma Chuanxiong, in the preparation of per 1000 units, the amount that the pseudo-ginseng activity composition that contains is amounted to into crude drug is 2000-8000 part, and the amount that the Rhizoma Chuanxiong active component that contains is amounted to into crude drug is 1000-4000 part.
Preferably Radix Notoginseng 3000-5000 part, Rhizoma Chuanxiong 1500-3000 part.
More preferably 4000 parts of Radix Notoginseng, 2000 parts of Rhizoma Chuanxiongs.
Described pseudo-ginseng activity composition is selected from: Radix Notoginseng total arasaponins, ginsenoside Rg
1, ginsenoside Rb
1, ginsenoside Re, Panax Notoginseng saponin R
1, Panax Notoginseng saponin R
2, dencichine, the Rhizoma Chuanxiong active component is selected from: the total effective ingredient of ferulic acid and ligustrazine, ligustrazine, ferulic acid.
Above pseudo-ginseng activity composition and Rhizoma Chuanxiong active component can extract with the method for routine and make, it can be crude extract, also can extract, extract preferably, described crude extract, generally without purification step, described extract generally passes through purification step, and pseudo-ginseng activity composition and Rhizoma Chuanxiong active component also can be bought from the market and obtain.
In more than forming, the weight of medicine is calculated with crude drug, per 1 part can be 1 gram, it also can be 1 kilogram or 1 ton, if with gram is unit, this prescription is formed the pharmaceutical preparation that can be made into 1000 units, and the pharmaceutical preparation of described 1000 units is meant, the final drug preparation of making, as make 1000 of capsule preparations, 1000 in tablet, granule 1000g, oral liquid 1000ml etc., also can make big packing as granule, as the 100-500 bag, specifically can be 100 bags, 125 bags, 200 bags, 250 bags, 500 bags etc., every bag can be used as taking dose 1 time.
More than form, can be made into the preparation of 50-1000 taking dose, as tablet, make 1000, each taking dose can be the 1-20 sheet, can take 50-1000 time altogether.As granule, make 125 bags, take the 1-2 bag at every turn, can take 62.5-125 time altogether.
More than form to be by weight as proportioning, when producing, can increase or reduce according to corresponding proportion, as large-scale production can be unit with the kilogram, or be unit with the ton, small-scale production can be unit with the milligram also, weight can increase or reduce, but the constant rate of the raw medicinal herbs weight proportion between each composition.
The ratio of above weight proportion obtains through science screening, for especial patient, and as serious symptom or light disease, fat or modest patient, the proportioning of the amount of can corresponding adjustment forming increases or reduces being no more than 100%, and drug effect is constant.
Pharmaceutical preparation of the present invention is to process through extraction or other modes by the raw material of Chinese medicine that above-mentioned prescription is formed, and makes active constituents of medicine, subsequently, with this material is raw material, adds the medicine acceptable carrier when needing, and makes according to the routine techniques of galenic pharmacy.Described active component can obtain by extracting raw material of Chinese medicine respectively, also can obtain by the co-extracted raw material of Chinese medicine, also can obtain by other modes, as: by pulverize, squeeze, calcine, grind, sieve, percolation, extraction, water are carried, alcohol extraction, ester are carried, methods such as ketone is carried, chromatography obtain, these active component can be the material of extractum form, can be that dry extract also can be a fluid extract, make different concentration according to the different needs decision of preparation.
Active constituents of medicine in the pharmaceutical preparation of the present invention, its shared percentage by weight in preparation can be 0.1-99.9%, all the other are the medicine acceptable carrier.Pharmaceutical preparation of the present invention exists with unit dosage form, and described unit dosage form is meant the unit of preparation, as every of tablet, capsular every capsules, every of injection etc., in the unit dose, the amount that contains active component is 5-800mg, preferably 20-500mg.
Pharmaceutical preparation of the present invention can be any pharmaceutically useful dosage form, and these dosage forms comprise: tablet, capsule, oral liquid, syrup, granule, pill, powder, unguentum, sublimed preparation, injection, suppository, cream, spray, drop pill, patch, slow releasing preparation, controlled release preparation.
Pharmaceutical preparation of the present invention, the preparation of its oral administration can contain excipient commonly used, such as binding agent, filler, diluent, tablet agent, lubricant, disintegrating agent, coloring agent, flavoring agent and wetting agent, can carry out coating to tablet in case of necessity.
The filler that is suitable for comprises cellulose, mannitol, lactose and other similar filler.Suitable disintegrating agent comprises starch, polyvinylpyrrolidone and starch derivatives, for example sodium starch glycollate.Suitable lubricant, for example magnesium stearate.The acceptable wetting agent of appropriate drug comprises sodium lauryl sulphate.
Can fill by mixing, the method that tabletting etc. are commonly used prepares solid oral composition.Mix repeatedly active substance is distributed in those compositionss of a large amount of filleies of whole use.
For injection, the liquid unit dosage forms of preparation contains active substance of the present invention and sterile carrier.According to carrier and concentration, this chemical compound can be suspended or dissolving.The preparation of solution is normally by being dissolved in active substance in a kind of carrier filter-sterilized before it is packed into a kind of suitable bottle or ampoule, sealing then.For example a kind of local anesthetic of adjuvant, antiseptic and buffer agent also can be dissolved in this carrier.In order to improve its stability, can be after the bottle of packing into that this compositions is freezing, and under vacuum, water is removed.
Pharmaceutical preparation of the present invention, when being prepared into medicament, optionally add suitable medicine acceptable carrier, described medicine acceptable carrier is selected from: mannitol, sorbitol, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, vitamin C, the EDTA disodium, EDTA calcium sodium, the alkali-metal carbonate of monovalence, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid, aminoacid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, cellulose and derivant thereof, alginate, gelatin, polyvinylpyrrolidone, glycerol, soil temperature 80, agar, calcium carbonate, calcium bicarbonate, surfactant, Polyethylene Glycol, cyclodextrin, beta-schardinger dextrin-, the phospholipid material, Kaolin, Pulvis Talci, calcium stearate, magnesium stearate etc.
Pharmaceutical preparation of the present invention, active component can extract two flavor medicines respectively, and extraction also can mix.When extracting respectively, method is as follows:
The preparation of Rhizoma Chuanxiong active component: take by weighing the Rhizoma Chuanxiong medical material, add 65～85% ethanol extractions twice, the time is 2 hours, 2 hours.Extracting solution has reclaimed ethanol post-heating water dissolution, filtered while hot, and filtrate is crossed AB-8 macroporous resin (or D while hot
101Macroporous resin), wash remove impurity after the absorption with water, reuse 30～40% ethanol elutions are collected eluent, and eluent concentrates, ferulic acid and the total effective ingredient of ligustrazine in dry the Rhizoma Chuanxiong;
The preparation of arasaponin: get and add 5～9 times of amount 65～75% alcohol reflux secondaries after pseudo-ginseng is pulverized respectively, the time is 1～3 hour at every turn, has extracted the back and has reclaimed ethanol, add water carry out water precipitating after centrifugal D
101Macroporous resin, the resin absorption post washes remove impurity with water, and reuse 40～80% ethanol carry out desorbing, collect eluent, have reclaimed the ethanol after drying and have got dry extract, and dried cream adds 85～95% ethanol extractions and gets Radix Notoginseng total arasaponins;
More than two kinds of active component mix, as active constituents of medicine, add the medicine acceptable carrier after, make pharmaceutical preparation by the galenic pharmacy routine techniques.
Medicine two compositions of the present invention have synergism, have coronary artery dilator, cerebrovascular, increase arteria coronaria, ischemic myocardium and cerebral blood flow, improve cerebral circulation, can also reduce myocardial oxygen consumption, reduce myocardial contraction, strengthen the hypoxia-bearing capability of heart and brain tissues, obviously to resisting myocardial ischemia and the effect of cerebral ischemia-reperfusion injury blood fat reducing in addition, anti peroxidation of lipid, removing oxygen-derived free radicals and effects such as anticoagulant and thrombosis.
Below beneficial effect by pharmacological evaluation explanation medicine of the present invention:
(every 1000ml, by Radix Notoginseng 4000g, Rhizoma Chuanxiong 2000g makes for Radix Notoginseng, Rhizoma Chuanxiong compound injection.Hereinafter to be referred as compound injection) pharmacological research
One, to the protective effect of myocardial ischemia
Get the Wistar rat, be divided into 4 groups at random, be i.e. blank group, model group, compound injection group, XUESHUANTONG ZHUSHEYE matched group.Model is irritated stomach according to group give distilled water 4ml/kg, all the other each groups are pressed the table 1 dosage corresponding medicinal liquid of lumbar injection respectively.Be administered once every day, continuous 6 days.Behind the last administration 1h, urethane (5%, face upward the position and fix by 20ml/kg) anesthetized rat, cut off animal skin along midsternal line, at left border of sternum 6～7 intercostal openings, extrude heart rapidly after, ligation at once left side heart coronary artery anterior descending branch root, heart is put back to the thoracic cavity, close thoracic cavity and stitching, take out heart behind the 6h ,-20 ℃ of preservations are spent the night.In the experimentation, respectively at (normally), ligation before the operation at once, 2h, 6h recording ecg after the ligation, observe that the ST section changes and myocardial ischemia improvement situation.Active and malonaldehyde (MDA) content of superoxide dismutase (SOD) is measured in the muscular tissue homogenate of coring.
Table 1 compound injection is to the influence of ST section change absolute value and myocardial ischemia scope
| Group | ????n | Dosage mg/kg | ST section change absolute value (x ± s) | Myocardial ischemia scope ratio | ||
| Ligation at once | ?2h | 6h | ||||
| Model group compound injection group XUESHUANTONG group | ????12 ????14 ????14 | ??- ??100 ??70 | ??2.48±1.23 ??2.43±1.16 ??2.50±1.31 | ?2.39±1.26 ?1.40±1.13 **△??1.78±1.33 * | 2.52±1.24 1.07±1.16 **△1.51±1.35 * | 0.34±0.07 0.15±0.09 **△0.23±0.11 * |
Annotate: compare with model group,
*P＜0.05,
*P＜0.01.
Compare with the XUESHUANTONG model group,
△P＜0.05.
As seen from the above table, compound injection is raised ECG ST section and is significantly improved behind the ligation 2h, and compound injection, XUESHUANTONG group are also significantly improved its variation during 6h, and the compound recipe group is better than XUESHUANTONG treatment group (P＜0.05) in the improvement of every index.And compound injection also is better than XUESHUANTONG group (P＜0.05) aspect the myocardial ischemia scope alleviating.
Table 2 compound injection is to the influence of rats with myocardial ischemia lipid peroxidation
| Group | ????n | Dosage (mg/kg) | SOD (U/g weight in wet base) | MDA (nmol/g weight in wet base) |
| Blank group model group compound injection group XUESHUANTONG group | ????15 ????12 ????14 ????14 | ??- ??- ??100 ??70 | ??495.46±14.24 **??345.17±13.28 ??472.74±18.54 **△????436.78±16.75 ** | ??126.4±16.8 **??348.6±14.9 ??162.7±17.6 **△△????206.4±20.4 ** |
Annotate: compare with model group,
*P＜0.01,
Compare with the XUESHUANTONG group,
△P＜0.05,
△ △P＜0.01.
As seen from the above table, compound injection can obviously improve rat heart muscle tissue SOD activity, reduces the level of myocardium MDA, and the prompting compound injection has the rat lipid peroxidation that resists myocardial ischemia to a certain degree, and its effect is better than the XUESHUANTONG ZHUSHEYE group.
In sum, compound injection has protective effect to the Acute Myocardial Ischemia in Rats that the ligation coronary artery is caused.
Two, to the protective effect of rat cerebral ischemia
(Wu Junfang, Shi Yiju, Liu Tianpei, berberine be to the protective effect of mice and rat cerebral ischemia, Chinese J Pharmacol Toxicol, 1995,9 (2): 100-103 for list of references.) described reversibility middle cerebral artery infraction (MCAO) method duplicates the focal cerebral ischemia in rats model.Behind the modeling 2h to the nervous symptoms of animal according to document (Bedexson JB.Pitts LH, Tsuji M, et al.Stroke, 1986,17:472.) mark, broken end is got brain after 24 hours, measures cerebral infarction scope, cerebral tissue superoxide dismutase (SOD) activity and malonaldehyde (MDA) content.
Table 3 compound injection is to the protective effect of rat cerebral ischemia
| Group | ????n | Dosage mg/kg | The nervous symptoms scoring | Cerebral infarction scope (%) | ??SOD ??(U/mgpr) | ??MDA ??(nmol/mgpr)) |
| Sham operated rats model group compound injection group XUESHUANTONG group | ????20 ????14 ????18 ????17 | ??- ??- ??100 ??70 | 0.7±1.2 **8.7±0.6 6.2±0.7 **△7.3±0.8 ** | ??0 **??13.6±3.2 ??8.4±1.1 **△????9.7±1.4 ** | ??46.8±8.8 **??21.7±6.4 ??35.8±6.1 **△????27.1±5.6 * | ??7.4±1.3 **??19.6±2.0 ??12.3±3.4 **△????15.6±2.5 * |
Annotate: compare with model group,
*P＜0.05,
*P＜0.01.
Compare with the XUESHUANTONG matched group,
△P＜0.05.
As seen from the above table, compound injection can obviously reduce the delayed ischemic neurological deficits grade scoring of rat model, obviously reduces the cerebral infarction scope, improves cerebral tissue SOD vigor, reduce MDA content (P all＜0.01), and its effect is better than XUESHUANTONG ZHUSHEYE (P＜0.05).Show that compound injection of the present invention has significant protective effect to MCAO cerebral ischemic model rat.
The specific embodiment:
Specific embodiment is as follows, includes but not limited to the following example.
Embodiment 1
The preparation of injection
The preparation method of active component is as follows:
The preparation of Rhizoma Chuanxiong active component: take by weighing Rhizoma Chuanxiong medical material 2000g, add 80% ethanol extraction twice, the time is 2 hours, 2 hours.Extracting solution has reclaimed ethanol post-heating water dissolution, filtered while hot, and filtrate is crossed the AB-8 macroporous resin while hot, wash remove impurity after the absorption with water, reuse 30% ethanol elution is collected eluent, eluent concentrates, ferulic acid and the total effective ingredient 71.9g of ligustrazine in dry the Rhizoma Chuanxiong;
The preparation of Radix Notoginseng total arasaponins: get and add 7 times of amounts, 5 times of amount 70% alcohol reflux secondaries after pseudo-ginseng 4000g pulverizes respectively, the time was respectively 2 hours, 2 hours, had extracted back recovery ethanol, add water carry out water precipitating after centrifugal D
101Macroporous resin, the resin absorption post washes remove impurity with water, reuse 70% ethanol carries out desorbing, collects eluent, reclaimed ethanol after drying under reduced pressure get dry extract, dried cream adds 90% ethanol extraction and gets Radix Notoginseng total arasaponins 20.9g;
Get pseudo-ginseng activity composition and Rhizoma Chuanxiong active component and add mannitol and water for injection, heated and stirred makes dissolving, transfers pH value, filters, add active carbon heating 15 minutes, cooling filters, and adds the volume that the injection water is settled to regulation, with the 0.2 μ m microporous filter membrane fine straining of sterilizing, degerming, bottling, lyophilization gets 1000 bottles (200mg/ bottles).
Embodiment 2
Capsule preparation method thereof,
The preparation method of active component is as follows:
The preparation of Rhizoma Chuanxiong active component: take by weighing Rhizoma Chuanxiong medical material 2000g, add 80% ethanol extraction twice, the time is 2 hours, 2 hours.Extracting solution has reclaimed ethanol post-heating water dissolution, filtered while hot, and filtrate is crossed the AB-8 macroporous resin while hot, wash remove impurity after the absorption with water, reuse 30% ethanol elution is collected eluent, eluent concentrates, ferulic acid and the total effective ingredient 72.5g of ligustrazine in dry the Rhizoma Chuanxiong;
The preparation of Radix Notoginseng total arasaponins: get and add 7 times of amounts, 5 times of amount 70% alcohol reflux secondaries after pseudo-ginseng 4000g pulverizes respectively, the time was respectively 2 hours, 2 hours, had extracted back recovery ethanol, add water carry out water precipitating after centrifugal D
101Macroporous resin, the resin absorption post washes remove impurity with water, reuse 70% ethanol carries out desorbing, collects eluent, reclaimed ethanol after drying under reduced pressure get dry extract, dried cream adds 90% ethanol extraction and gets Radix Notoginseng total arasaponins 21.6g;
Get that two kinds of active component of Radix Notoginseng and Rhizoma Chuanxiong are pulverized, behind the mix homogeneously, add a certain amount of adjuvant mix homogeneously and incapsulate, make 1000 capsules (0.30g/ grain), reinstall in the bottle after aluminum-plastic packaged and seal.
Embodiment 3
Process for producing granula,
The preparation method of active component is as follows:
The preparation of Rhizoma Chuanxiong active component: take by weighing Rhizoma Chuanxiong medical material 1000g, add 80% ethanol extraction twice, the time is 2 hours, 2 hours.Extracting solution has reclaimed ethanol post-heating water dissolution, filtered while hot, and filtrate is crossed the AB-8 macroporous resin while hot, wash remove impurity after the absorption with water, reuse 30% ethanol elution is collected eluent, eluent concentrates, ferulic acid and the total effective ingredient 36.5g of ligustrazine in dry the Rhizoma Chuanxiong;
The preparation of Radix Notoginseng total arasaponins: get and add 7 times of amounts, 5 times of amount 70% alcohol reflux secondaries after pseudo-ginseng 8000g pulverizes respectively, the time was respectively 2 hours, 2 hours, had extracted back recovery ethanol, add water carry out water precipitating after centrifugal D
101Macroporous resin, the resin absorption post washes remove impurity with water, reuse 70% ethanol carries out desorbing, collects eluent, reclaimed ethanol after drying under reduced pressure get dry extract, dried cream adds 90% ethanol extraction and gets Radix Notoginseng total arasaponins 42.6g;
After getting two kinds of active component pulverizing of Radix Notoginseng and Rhizoma Chuanxiong, mix homogeneously, add a certain amount of adjuvant mixing and all make the 1000g granule, the packaging bag of packing into.
Embodiment 4
Method for preparing tablet thereof,
The preparation method of active component is as follows:
The preparation of Rhizoma Chuanxiong active component: take by weighing Rhizoma Chuanxiong medical material 4000g, add 80% ethanol extraction twice, the time is 2 hours, 2 hours.Extracting solution has reclaimed ethanol post-heating water dissolution, filtered while hot, and filtrate is crossed the AB-8 macroporous resin while hot, wash remove impurity after the absorption with water, reuse 30% ethanol elution is collected eluent, eluent concentrates, ferulic acid and the total effective ingredient 144.5g of ligustrazine in dry the Rhizoma Chuanxiong;
The preparation of Radix Notoginseng total arasaponins: get and add 7 times of amounts, 5 times of amount 70% alcohol reflux secondaries after pseudo-ginseng 2000g pulverizes respectively, the time was respectively 2 hours, 2 hours, had extracted back recovery ethanol, add water carry out water precipitating after centrifugal D
101Macroporous resin, the resin absorption post washes remove impurity with water, reuse 70% ethanol carries out desorbing, collects eluent, reclaimed ethanol after drying under reduced pressure get dry extract, dried cream adds 90% ethanol extraction and gets Radix Notoginseng total arasaponins 11.2g;
After getting two kinds of active component pulverizing of Radix Notoginseng and Rhizoma Chuanxiong, mix homogeneously, add a certain amount of adjuvant mixing and all make 1000 tablets of tablets, packing.
Claims (7)
1. pharmaceutical preparation for the treatment of cardiovascular and cerebrovascular disease, it is characterized in that, contain the pseudo-ginseng activity composition of effective dose and the Rhizoma Chuanxiong active component of effective dose, the pseudo-ginseng activity composition is made with Radix Notoginseng, the Rhizoma Chuanxiong active component is made with Rhizoma Chuanxiong, in the preparation of per 1000 units, the amount that the pseudo-ginseng activity composition that contains is amounted to into crude drug is 2000-8000 part, and the amount that the Rhizoma Chuanxiong active component that contains is amounted to into crude drug is 1000-4000 part.
2. the pharmaceutical preparation of claim 1 is characterized in that, in the preparation of per 1000 units, the amount that the pseudo-ginseng activity composition that contains is amounted to into crude drug is 3000-5000 part, and the amount that the Rhizoma Chuanxiong active component that contains is amounted to into crude drug is 1500-3000 part.
3. the pharmaceutical preparation of claim 1 is characterized in that, in the preparation of per 1000 units, the amount that the pseudo-ginseng activity composition that contains is amounted to into crude drug is 4000 parts, and the amount that the Rhizoma Chuanxiong active component that contains is amounted to into crude drug is 2000 parts.
4. any one pharmaceutical preparation of claim 1-3 is characterized in that described pseudo-ginseng activity composition is selected from: Radix Notoginseng total arasaponins, ginsenoside Rg
1, ginsenoside Rb
1, ginsenoside Re, Panax Notoginseng saponin R
1, Panax Notoginseng saponin R
2, dencichine, the Rhizoma Chuanxiong active component is selected from: the total effective ingredient of ferulic acid and ligustrazine, ligustrazine, ferulic acid.
5. the pharmaceutical preparation of claim 1 is selected from injection, tablet, granule, capsule, drop pill or pellet.
6. the application of the pharmaceutical preparation of claim 1 in the medicine of preparation treatment cardiovascular and cerebrovascular disease.
7. the preparation method of the pharmaceutical preparation of claim 1 is characterized in that, the process following steps:
The preparation of Rhizoma Chuanxiong active component: take by weighing the Rhizoma Chuanxiong medical material, add 65～85% ethanol extractions twice, the time is 2 hours, 2 hours.Extracting solution has reclaimed ethanol post-heating water dissolution, filtered while hot, and filtrate is crossed AB-8 macroporous resin (or D while hot
101Macroporous resin), wash remove impurity after the absorption with water, reuse 30～40% ethanol elutions are collected eluent, and eluent concentrates, ferulic acid and the total effective ingredient of ligustrazine in dry the Rhizoma Chuanxiong;
The preparation of pseudo-ginseng activity composition: get and add 5～9 times of amount 65～75% alcohol reflux secondaries after pseudo-ginseng is pulverized respectively, the time is 1～3 hour at every turn, has extracted the back and has reclaimed ethanol, add water carry out water precipitating after centrifugal D
101Macroporous resin, the resin absorption post washes remove impurity with water, and reuse 40～80% ethanol carry out desorbing, collect eluent, have reclaimed the ethanol after drying and have got dry extract, and dried cream adds 85～95% ethanol extractions and gets Radix Notoginseng total arasaponins;
More than two kinds of active component mix, as active constituents of medicine, this active component with make preparation after the medication medication acceptable carrier mixes.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510004925 CN1679698A (en) | 2005-01-28 | 2005-01-28 | Medicinal preparation containing notoginseng and lovge rhizome for treating cardio-cerebral blood vessel diseases and its preparing method |
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| CN 200510004925 CN1679698A (en) | 2005-01-28 | 2005-01-28 | Medicinal preparation containing notoginseng and lovge rhizome for treating cardio-cerebral blood vessel diseases and its preparing method |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102512470A (en) * | 2012-01-05 | 2012-06-27 | 成都中医药大学 | Pharmaceutical composition for treating cerebrovascular and cardiovascular diseases as well as preparation method and application |
| CN102940702A (en) * | 2012-10-31 | 2013-02-27 | 成都医路康医学技术服务有限公司 | Medicine composition for treating cardia-cerebrovascular diseases |
| CN103039970A (en) * | 2012-11-30 | 2013-04-17 | 湛江市八和药业有限公司 | Active ingredients of anti-hypoxia and anti-fatigue nutritional health-care product and preparation method for active ingredients |
| CN112294855A (en) * | 2020-12-01 | 2021-02-02 | 广州白云山奇星药业有限公司 | Dispersible tablet for treating coronary heart disease and preparation method thereof |
| CN115300553A (en) * | 2018-07-18 | 2022-11-08 | 中国医学科学院药物研究所 | Pharmaceutical composition, preparation method and application of pharmaceutical composition in treatment of cerebral arterial thrombosis |
-
2005
- 2005-01-28 CN CN 200510004925 patent/CN1679698A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102512470A (en) * | 2012-01-05 | 2012-06-27 | 成都中医药大学 | Pharmaceutical composition for treating cerebrovascular and cardiovascular diseases as well as preparation method and application |
| CN102512470B (en) * | 2012-01-05 | 2013-08-28 | 成都中医药大学 | Pharmaceutical composition for treating cerebrovascular and cardiovascular diseases as well as preparation method and application |
| CN102940702A (en) * | 2012-10-31 | 2013-02-27 | 成都医路康医学技术服务有限公司 | Medicine composition for treating cardia-cerebrovascular diseases |
| CN102940702B (en) * | 2012-10-31 | 2014-05-28 | 成都医路康医学技术服务有限公司 | Medicine composition for treating cardia-cerebrovascular diseases |
| CN103039970A (en) * | 2012-11-30 | 2013-04-17 | 湛江市八和药业有限公司 | Active ingredients of anti-hypoxia and anti-fatigue nutritional health-care product and preparation method for active ingredients |
| CN103039970B (en) * | 2012-11-30 | 2016-01-20 | 湛江市八和药业有限公司 | A kind of active component and preparation method thereof of nutrient and healthcare products with resist oxygen lack, antifatigue |
| CN115300553A (en) * | 2018-07-18 | 2022-11-08 | 中国医学科学院药物研究所 | Pharmaceutical composition, preparation method and application of pharmaceutical composition in treatment of cerebral arterial thrombosis |
| CN112294855A (en) * | 2020-12-01 | 2021-02-02 | 广州白云山奇星药业有限公司 | Dispersible tablet for treating coronary heart disease and preparation method thereof |
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