CN1810268A - Apoplexy treating medicine composition - Google Patents
Apoplexy treating medicine composition Download PDFInfo
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Abstract
The present invention relates to one kind of medicine composition and its preparation and application. The medicine composition consists of Chinese medicinal materials or their extracts, including shortscape fleabane herb, 14-29 weight portions, red sage 1-17 weight portions, astragalus root 8-17 weight portions and borneol 0.06-0.13 weight portions. The medicine composition is used for treating apoplexy.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition, specifically, is a kind of Chinese medicine composition that is used for the treatment of the apoplexy disease.
Background technology
Apoplexy is the appellation of the traditional Chinese medical science to cerebrovascular accident type disease.It is a kind of commonly encountered diseases and frequently-occurring disease that is caused unusually by vascular factor, blood factor and blood flow factor.It is hurried with onset, dysphonia, disturbance of consciousness, facial hemiparalysis and hemiplegia etc. are principal character.Its sickness rate, mortality rate and disability rate are all quite high, and about 60-80% leaves deformity in various degree among the survivor after the apoplexy, and its quality of life is had a strong impact on, and cause great economy and mental burden for society and family.
In the colony that apoplexy disables, be person more than 50 years old more than 85%, and its ratio increase with the growth at age.These patients mostly are positive QI-insufficiency, brain internal organs function goes down in various degree, even suffer from one or more complication, thereby at when treatment strengthening the body resistance targetedly, adjust immunity of organisms, to reach the purpose for the treatment of both the principal and secondary aspects of a disease, for this reason, many in the last few years medical workers compare research respectively to the combination curative effect of the more Radix Salviae Miltiorrhizae Injection of clinical practice, fleabane injection and Radix Astragali injection.
The medicine that is used for the treatment of apoplexy now is a lot, as: NAOSHUAN KANGFU JIAONANG, NAOXUESHUAN PIAN etc., in the clinical practice, these medicines are not only treated cerebral hemorrhage but also treat cerebral blood stasis, but such medicine is not special for treating apoplexy later stage (convalescent period), so far the also medicine in neither one special for treating apoplexy later stage (convalescent period), therefore the sick convalescent medicine of a kind of treatment apoplexy is developed in market in urgent need, its therapeutic purposes are the recoveries that promote function, reduce sequela, improve patient's ability to work and quality of life, prevent recurrence.So at apoplexy sequela, especially brain network numbness type apoplexy sequela is implemented treating both the principal and secondary aspects of a disease, having systematic treating side's medicine that blood circulation promoting and blood stasis dispelling, supplementing qi and invigorating vasculum function set up is the main task of nowadays developing the medication of treatment apoplexy.
Summary of the invention
One object of the present invention is the medicine that a kind of Chinese medicine composition is provided and contains said composition, and this medicine can be treated the apoplexy disease, is particularly useful for the convalescent period of apoplexy disease.
In the investigative test in early stage, the inventor then goes it according to the stasis of blood, the treatment rule of deficiency syndrome should be treated by tonifying method, on single Herba Erigerontis preparation basis, increase invigorating blood circulation of Radix Salviae Miltiorrhizae, Borneolum Syntheticum, add the QI invigorating of the Radix Astragali, become the compound recipe of blood circulation promoting and blood stasis dispelling, supplementing qi and invigorating vasculum, be intended to residence and mend in leading to, be suitable for the rehabilitation conditioning.In ensuing research; we are surprised to find; being added in of Borneolum Syntheticum improved mice to the tolerance effect of cerebral hypoxia ischemia, cerebral ischemia causes that the protective effect aspect of cerebral edema all is significantly improved to imperfection; this is that those skilled in the art are unpredictable; therefore the inventor expect above-mentioned prescription be not subjected to traditional rule, side separate limit, obtained beneficial effect all be experimental results show that by pharmacological effect.
In order to achieve the above object, the invention provides a kind of Chinese medicine composition is compound breviscpini, is made by Herba Erigerontis 14-29 part, Radix Salviae Miltiorrhizae 1-17 part, Radix Astragali 8-17 part and Borneolum Syntheticum 0.06-0.13 part.Described umber all by weight.
In the present composition, can select flavour of a drug directly to be ground into powder and be used as medicine, the form of extract that also can be equivalent to above-mentioned Chinese crude drug crude drug amount is used as medicine, and also can select the part fecula and all the other components are used as medicine with extract.Therefore, the activity of pharmaceutical composition of the present invention is formed and is comprised the former powder of medical material, fat or water solubility extract, effective site or effective ingredient.For example, comprise described active the composition:
1) Herba Erigerontis herb powder, ethanol extract, effective site breviscapine or effective ingredient such as lamp-dish flower acetic, single, double caffeoylquinic acids;
2) the dry root and rhizome powder of labiate Radix Salviae Miltiorrhizae or water extract or the total phenolic acid of effective site or effective ingredient such as danshensu, salvianolic acid B, tanshinone;
3) dry root powder of leguminous plant Radix Astagali or Radix Astragali, or water extract or effective site Radix Astragali total glycosides, astragalus polysaccharides or effective ingredient astragaloside;
4) processed goods of the resin of Dipterocarpaceae Borneolum Syntheticum and volatile oil (being borneol), or by Camphora, Lignum Pini Nodi wet goods through chemosynthesis and composite (being borneolum syntheticum or BORNEOLUM SYNTHETICUM).
In a scheme of the present invention, preferably adopt the extract of Herba Erigerontis, Radix Salviae Miltiorrhizae, the Radix Astragali and the powder of Borneolum Syntheticum (fine powder).
In a preferred embodiment of the invention, described pharmaceutical composition is made by following proportion raw material: Herba Erigerontis 14-29 part, Radix Salviae Miltiorrhizae 8-17 part, Radix Astragali 8-17 part and Borneolum Syntheticum 0.06-0.13 part; More preferably Herba Erigerontis 20-23 part, Radix Salviae Miltiorrhizae 12-14 part, Radix Astragali 12-14 part and Borneolum Syntheticum 0.09-0.11 part; With most preferably be 5 parts of 1089 parts of Herba Erigerontiss, 653 parts of Radix Salviae Miltiorrhizaes, 653 parts of the Radixs Astragali and Borneolum Syntheticums.
The present invention also provides manufacturing method for above mentioned medicine, comprising: with the Herba Erigerontis alcohol extraction, concentrate, alkali is molten, and acid precipitation filters, and must precipitate and filtrate; The Radix Salviae Miltiorrhizae water extraction, the alcohol precipitation obtains supernatant; Merging filtrate liquid and supernatant with the weak polar solvent extraction, obtain the extract clear paste; Radix Astragali water extraction, the alcohol precipitation, solution concentration becomes extractum; With borneol powder mix with extractum, clear paste and precipitation, dry and pulverize.
Those skilled in the art can take the circumstances into consideration to change to above-mentioned steps according to the physicochemical property and the pharmacological action of different Chinese crude drugs, definite with screening by analysis optimization technology.For example, Borneolum Syntheticum is the volatility medical material, descends, so select directly to pulverize to be used as medicine, also can be used as medicine behind cyclodextrin inclusion compound if through heating extraction its drug effect volatilization is scattered and disappeared; Investigation through extraction process, find that Herba Erigerontis is with ethanol extraction, especially the effective ingredient optimum that obtains of reflux, extract,, the Radix Salviae Miltiorrhizae and the Radix Astragali are then selected water extract-alcohol precipitation, consider the needs of work simplification, and reduce supplementary product consumption, the technology of the alcohol precipitation remove impurity reservation supernatant of especially preferred 40% or more (more preferably about 60%) concentration, pharmacology pharmacodynamic experiment showed, that the resultant effect of this process route is preferable.It is that content with paste-forming rate and lamp-dish flower acetic is index that decocting boils technical conditions (optimum technology parameter) with alcohol reflux, adopts three factors, three water-glasses to carry out that orthogonal test determines.
Specifically, described preparation method may further comprise the steps:
Herba Erigerontis adds ethanol (for example concentration 60%) reflux, extract, at least once (preferably twice), at least 0.5 hour at every turn (preferred 2 hours), merge extractive liquid,, concentrating under reduced pressure reclaims ethanol to about 1.13 (preferably about 45 ℃) of concentrated solution relative density, sodium hydroxide solution (preferred about 10%) with low concentration is transferred pH6～7, leave standstill (preferred about 24 hours), filter, filtrate is transferred pH2～3 with the dilute sulfuric acid test solution, leave standstill (preferred about 48 hours), filter, it is standby that precipitation washes (preferred 2 times) with water, filtrate for later use;
Radix Salviae Miltiorrhizae decocts with water (preferably twice), at least 0.5 hour at every turn (preferred 2 hours), medicinal liquid merges, and is evaporated to the clear paste that relative density is approximately 1.07～1.10 (preferably at 65 ℃), places room temperature, stir and add ethanol down, make ethanol content reach (preferred about 60%) more than 40%, leave standstill (preferred about 24 hours), filter, filtrate decompression is concentrated into relative density and is about 1.18 (preferably at 50 ℃) clear paste, transfers pH2～3;
Radix Salviae Miltiorrhizae clear paste and Herba Erigerontis filtrate merge, and with water saturation ethyl acetate extraction at least 1 time (preferred more than 2 times, more preferably 4 times), combined ethyl acetate extract, reclaim under reduced pressure ethyl acetate to concentrated solution relative density is about 1.12 (preferably at 45 ℃), and is standby;
The Radix Astragali decocts with water at least once (preferred 2 times, each 2 hours), medicinal liquid merges, and filters, and filtrate decompression is concentrated into relative density and is about 1.10 (preferably at 65 ℃) clear paste, be placed to room temperature, add ethanol and make ethanol content reach (preferred about 60%) more than 40%, left standstill 24 hours, filter, filtrate is concentrated into relative density and is about 1.35 (preferably at 55 ℃) clear paste, and is standby; Precipitation is dissolved in water and puts heating in water bath it is fully dissolved, filtered while hot, supernatant concentration to relative density is about 1.18 (preferably at 55 ℃), adding ethanol reaches more than 50% ethanol content (preferably to be about 80%), leave standstill (preferred more than 12 hours, more preferably from about 48 hours), filter, filtrate discards, and precipitation merges with the alcohol deposit fluid clear paste;
The precipitation of the above-mentioned Radix Astragali and alcohol deposit fluid clear paste merge thing and together incorporate in Herba Erigerontis precipitation, the ethyl acetate clear paste, put in the vacuum drying oven, and drying under reduced pressure is pulverized, and sneaks into the Borneolum Syntheticum fine powder and promptly obtains the present composition.
Mixed three kinds of extracts after also drying under reduced pressure can being pulverized are ground into fine powder, add appropriate amount of auxiliary materials and mix, granulate, and sneak into the Borneolum Syntheticum fine powder again, and encapsulated, content generally is about 0.2～0.7g/ grain, preferred 0.4～0.5g/ grain.
Another object of the present invention provides the purposes of aforementioned pharmaceutical compositions in the treatment apoplexy.Above-mentioned composition of the present invention be at stroke in convalescent stage mark dispel in fact, weakened body resistance be systematic treating side's medicine that main syndrome is set up, it can implement treating both the principal and secondary aspects of a disease to apoplexy sequela, especially brain network numbness type apoplexy sequela, has blood circulation promoting and blood stasis dispelling, the function of supplementing qi and invigorating vasculum.
Studies show that, (be the above dosage continuous oral administration 7 days of compound breviscpini capsule 4.5g crude drug/kg), the rising of biologically active pdgf in the body is had significant inhibitory effect by every kg body weight oral administered compound Herba Erigerontis capsule 4.5g crude drug; The above dosage successive administration of compound breviscpini capsule 4.5g crude drug/kg 5 days can improve Mice Auricle venule and arteriole caliber, and micro-circulation flow rate is increased; The above dosed administration of compound breviscpini capsule 2.25g crude drug/kg 8 days also can reduce blood stasis model rat whole blood viscosity, blood plasma viscosity and erythrocyte aggregation index.Middle and high dosage group also can reduce the low cut of whole blood to viscosity, shows that this medicine improves significantly to the hemorheological property tool of blood stasis model animal; The above dosage continuous oral of compound breviscpini capsule 1.8g crude drug/kg administration five days can make the focal cerebral infarct size of rat significantly dwindle, and behavior disorder is also corresponding to be significantly improved.
Simultaneously, the pathology experiment shows, compares with matched group, and the compound breviscpini capsule of high dose has significantly alleviated the pathological change of the local infarction kitchen range of animal brain, and is parallel with contrast medicine nimodipine.The concordance of this pharmacology and pathological examination has proved that further this medicine has significant protective effect to the local infarction kitchen range of brain.
Pharmaceutical composition of the present invention can be used for apoplexy sequela: hemiplegia, and speech is unfavorable, facial hemiparalysis, or shortness of breath and fatigue etc. is arranged.Can improve apoplexy blood stasis due to qi deficiency syndrome greatly, to also having clear improvement before and after the symptom of apoplexy and blood pressure, the treatment of hemorheology part index number, and determined curative effect, safe and effective.The tcm syndrome curative effect that experiment showed, medicine of the present invention obviously is better than existing Chinese patent medicine.With the capsule is example (content of general 1000 capsules is equivalent to crude drug total amount 2400 gram, i.e. 2.4g crude drug/grains), and clinical recommended dose is 3/time, 3 times/day.
Can adopt conventional adjuvant, according to standard preparation technology, aforementioned pharmaceutical compositions is made any dosage form known in the art, be preferably peroral dosage form, it is that on the pharmacy meaning all can supply oral dosage form, for example granule, hard/soft capsule, tablet, powder, dispersible tablet, oral cavity disintegration tablet, pill, drop pill or oral liquid, preferred particulates agent, capsule, tablet, dispersible tablet, oral cavity disintegration tablet, pill, drop pill; More preferably tablet, pill or hard/soft capsule.
The physical and chemical identification of the present composition and medicine: Herba Erigerontis is the monarch drug in this prescription, so with the content of lamp-dish flower acetic major quality controlling index as this product, therefore adopt high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000) to measure the content of lamp-dish flower acetic in the product in the present invention, this method sensitivity, favorable reproducibility.With capsule of the present invention is example, contains lamp-dish flower acetic in the product of the present invention and should be no less than the 3.7mg/ grain, is preferably the 5-18mg/ grain.
The pharmacology pharmacodynamic experimental study
The scarce flavor of the compound breviscpini capsule of compound breviscpini capsule that this test makes embodiment (Herba Erigerontis, Radix Salviae Miltiorrhizae, the Radix Astragali and Borneolum Syntheticum) and same component ratio (Herba Erigerontis, the Radix Astragali and Borneolum Syntheticum), compound breviscpini capsule scarce flavor 1 (Herba Erigerontis, Radix Salviae Miltiorrhizae and the Radix Astragali) and compound breviscpini capsule lack 2 (Herba Erigerontis, Radix Salviae Miltiorrhizae and the Borneolum Syntheticums) of distinguishing the flavor of and have carried out following research respectively.The result is as follows:
1. to the thrombotic influence of rat experiment
1.1 to the thrombotic influence of rat neck artery-vein blood flow coronary artery bypass grafting
Experiment is undertaken by literature method, male rat, cause the bypass of neck artery-vein, behind the gastric infusion 40 minutes, Herba Clinopodii in behind the open blood flow 15min takes out silk thread rapidly, with filter paper inhale remove excessive moisture after torsion balance weigh, the experiment that hockets of gross weight-silk thread weight=wet weight of thrombus, administration group and matched group.
The table 1 pair rat neck artery-vein thrombotic influence of blood flow coronary artery bypass grafting (n=10)
| Group and dosage | Wet weight of thrombus (X ± Smg) | Suppression ratio |
| Dosage 2.25g/kg compound breviscpini capsule low dosage 4.5g/kg in the matched group HUATUO ZAIZAO WAN 8g/kg compound breviscpini capsule in high dose 1.35g/kg compound breviscpini capsule | 115.7±45.64 81.3±30.92 77.1±31.24 66.5±13.58 * 70.9±38.39 * | 29.8％ 31.6％ 41.2％ 38.5％ |
Compare with matched group
*P＜0.05
The result shows, compares with matched group, and each administration group all can make wet weight of thrombus alleviate, and wherein middle and high dosage group of compound breviscpini capsule and matched group relatively have significant difference (P＜0.05).
1.2 to the thrombotic influence of rats in vitro
With the rat random packet about body weight 200g, the ig administration is 10 days continuously, last administration 40 minutes, animal is with pentobarbital sodium 50mg/kg intraperitoneal injection of anesthesia, in the vinyon ring with silication, put on formation of XSN-R type external thrombus and the platelet adhesion double-purpose instrument and measure, take off behind the rotation 10min and measure wet weight of thrombus (blotting the back with filter paper measures) and thrombosis dry weight (65 ℃ of baking 20min) respectively.The result shows, each dosage group of compound breviscpini capsule and scarce flavor group (Herba Erigerontis, the Radix Astragali and Borneolum Syntheticum) all make wet weight of thrombus alleviate, in, heavy dose of group can make the thrombosis dry weight alleviate (P＜0.05), but lack flavor group 1 (Herba Erigerontis, Radix Salviae Miltiorrhizae and the Radix Astragali) make this index effect that wet weight of thrombus alleviates obviously not as each dosage group of compound breviscpini capsule and scarce flavor group.
The influence that table 2 pair rats in vitro thrombosis forms (X ± S)
| Group and dosage | Number of animals | Wet weight of thrombus (mg) | The thrombosis dry weight |
| Matched group | 8 | 119.66±43.08 | 74.57±38.97 |
| Huatuo zaizao pill 8g/kg compound breviscpini capsule 1.35g/kg compound breviscpini capsule 2.25g/kg compound breviscpini capsule 4.50g/kg compound breviscpini capsule lacks flavor compound breviscpini capsule and lacks flavor 1 | 8 10 10 10 10 10 | 83.77±38.79 76.31±21.57 * 63.49±18.43 ** 71.75±23.41 * 73.11±24.33 81.98±28.73 | 51.07±31.67 41.04±16.18 31.38±11.81 * 37.58±13.38 * 37.58±13.38 * 49.27±26.57 |
*P＜0.05
*Compare with matched group P＜0.01
In rat artery-thrombotic experiment of venous blood flow coronary artery bypass grafting, with model control group relatively, the wet weight of thrombus that large, medium and small three dosage groups of compound breviscpini capsule and matched group form all has and alleviates.Compare the above dosage group of compound breviscpini capsule 1.35g crude drug/kg P＜0.05 with model control group; In rats in vitro thrombosis process, each administration group of compound breviscpini capsule and scarce flavor group all make wet weight of thrombus than matched group notable difference (P＜0.05) more also be arranged, though and the compound breviscpini capsule lacks 1 group of wet weight of thrombus that forms with matched group of flavor and compares and alleviate, but do not have significant difference (P＞0.05), its effect is similar to positive control drug.
1.3 influence to the formation of mice thrombus in vivo
The above dosage continuous oral of compound breviscpini capsule 1.35g crude drug/kg administration 5 days obviously suppresses the mice thrombus in vivo, and the hemiplegia that improves in the mice 15 minutes is recovered number, shows that this medicine forms thrombus in vivo and has obvious antagonism.
2, to the protective effect of rat test cerebral ischemia
2.1 influence to brain water content
With body weight 150-180g rat random packet, 1hr ig every day (oral) is administered once before preceding 9 days of test and art, and the ligation bilateral carotid arteries causes the incomplete ischemia model of acute experiment, put to death animal, get brain and weigh, roasting to constant weight in 110 ℃ of baking boxs, calculate brain water content (%).
The influence of table 3 pair experimental cerebral ischemia rat brain water content
| Group and dosage | Number of animals | Brain water content (%) (X ± S) |
| Normal group cerebral ischemic model huatuo zaizao pill 8g/kg compound breviscpini capsule 1.8g/kg compound breviscpini capsule 2.25g/k compound breviscpini capsule 4.5g/kg compound breviscpini capsule lacks flavor 4.5g/kg compound breviscpini capsule and lacks flavor 1 (4.5g/kg) | 10 10 10 10 10 10 10 10 | 72.4±2.94 76.1±2.55 △ 72.9±3.56 69.6±4.14 * 66.1±2.99 ** 63.0±3.10 ** 71.4±4.01 72.3±3.65 |
*Compare with brain blood model P＜0.05;
△P＜0.01 cerebral ischemic model and normal control group are relatively
By the result as can be known, above dosage group of 1.8g crude drug/kg and cerebral ischemic model group compare, and brain water content obviously reduces (P＜0.05), shows that its cerebral edema that cerebral ischemia causes to imperfection has significant protective effect.Simultaneously, data also prove, the scarce flavor group cerebral edema that cerebral ischemia causes to imperfection that does not contain the scarce flavor 1 (Herba Erigerontis, Radix Salviae Miltiorrhizae and the Radix Astragali) of Borneolum Syntheticum and do not contain Radix Salviae Miltiorrhizae does not have obvious protective effect.
In addition, the above dosage continuous oral of evidence compound breviscpini capsule 1.8g crude drug/kg administration 7 days can obviously prolong the mouse brain circulatory disturbance time-to-live, and high, middle dosage group has prolonged about 3 times and 2 times than matched group respectively.Show that this medicine can increase the blood flow of mouse brain circulatory disturbance, thereby improved, and the compound breviscpini capsule lacks flavor 1 owing to lack Borneolum Syntheticum, and do not contain the scarce flavor group of Radix Salviae Miltiorrhizae, all do not demonstrate dependent interaction owing to lack Radix Salviae Miltiorrhizae to cerebral hypoxia ischemia animal tolerance effect.
3, to normal and the influence of blood stasis rat platelet aggregation
3.1 influence to normal rat platelet aggregation
Get body weight 150-200g rat random packet, administration 10 days, 1hr after the last administration, abdominal aortic blood, the sodium citrate anticoagulant, separate platelet rich plasma (PRP) and platelet poor plasma (PPP), with SPA-4 type platelet aggregation with mensuration platelet 3min maximum agglutination rate (ADP with 1mM is a derivant).
The influence of table 4. pair normal rat platelet aggregation (X ± S)
| Group and dosage | Number of animals | 3 minutes maximum agglutination rate (%) |
| Normal group huatuo zaizao pill 8g/kg compound breviscpini capsule 1.35g/kg compound breviscpini capsule 2.25g/k compound breviscpini capsule 4.5g/kg compound breviscpini capsule lacks flavor 1 (4.5g/kg) compound breviscpini capsule and lacks flavor 2 (4.5g/kg) | 10 10 10 10 10 10 10 | 72.1±19.2 48.5±32.4 50.9±16.70 46.0±21.15 41.4±25.86 * 54.3±24.57 52.2±20.55 |
*Compare with matched group P＜0.05
The result shows, each group of administration all has certain inhibitory action to normal rat platelet aggregation, wherein the heavy dose of group of administration relatively acts on obviously (P＜0.05) with matched group, and a little less than the scarce flavor 2 (Herba Erigerontis, Radix Salviae Miltiorrhizae and Borneolum Syntheticum) that does not contain the scarce flavor 1 (Herba Erigerontis, Radix Salviae Miltiorrhizae and the Radix Astragali) of Borneolum Syntheticum and do not contain the Radix Astragali acts on slightly.
3.2. influence to the blood stasis rat platelet aggregation
Rat is divided into 9 groups at random, the ig administration is 8 days continuously, all the other each treated animals are only pressed literature method subcutaneous injection 0.1% epinephrine 0.1ml/ except that first group, after stimulation causes " blood stasis " state with frozen water, continue ig administration 2 days, administration is 10 days altogether, and 1hr puts to death animal and gets blood system from PRP and PPP mensuration platelet aggregation after the last administration.
The influence of table 5. pair blood stasis rat platelet aggregation
| Group and dosage | Number of animals | 3 minutes maximum agglutination rate (%) (X ± S) |
| Zheng control group blood stasis model Zu huatuo zaizao pill 8g/kg compound breviscpini capsule 1.35g/kg compound breviscpini capsule 2.25g/k compound breviscpini capsule 4.5g/kg compound breviscpini capsule lacks flavor (4.5g/kg) compound breviscpini capsule and lacks the scarce flavor of flavor 1 (4.5g/kg) compound breviscpini capsule 2 (4.5g/kg) | 8 8 8 8 8 8 8 8 8 | 62.7±1.11 81.5±8.7 △△ 67.6±10.7 * 71.0±7.7 69.5±13.8 64.8±8.1 *** 72.6±6.7 74.6±8.7 71.9±8.2 |
Compare with the normal control group
△ △P＜0.01; Compare with the blood stasis model group
*P＜0.05;
Compare with the blood stasis model group
* *P＜0.001
By table 5 result as can be known, the heavy dose of group of HUATUO ZAIZAO WAN and compound breviscpini capsule more all has the effect of obvious suppression platelet aggregation with the blood stasis model group, and do not contain the scarce flavor group (Herba Erigerontis, Radix Salviae Miltiorrhizae and the Radix Astragali) of Radix Salviae Miltiorrhizae, the scarce flavor 2 (Herba Erigerontis, Radix Salviae Miltiorrhizae and Borneolum Syntheticum) that does not contain the scarce flavor 1 (Herba Erigerontis, Radix Salviae Miltiorrhizae and the Radix Astragali) of Borneolum Syntheticum and do not contain the Radix Astragali does not all have the effect of obvious suppression platelet aggregation.
Simultaneously, this test has also been carried out same pharmacological effect research respectively to the compound breviscpini capsule (Herba Erigerontis, Radix Salviae Miltiorrhizae, the Radix Astragali and Borneolum Syntheticum) of different component proportioning, the result shows, when having only the ratio of Herba Erigerontis 14-29 part, Radix Salviae Miltiorrhizae 8-17 part, Radix Astragali 8-17 part and Borneolum Syntheticum 0.06-0.13 part to carry out prescription, the effect of its compound capsule is remarkable; When the prescription ratio was Herba Erigerontis 20-23 part, Radix Salviae Miltiorrhizae 12-14 part, Radix Astragali 12-14 part and Borneolum Syntheticum 0.09-0.11 part, drug effect obviously was better than the compound recipe of other proportionings; When most preferably being 5 parts of 1089 parts of Herba Erigerontiss, 653 parts of Radix Salviae Miltiorrhizaes, 653 parts of the Radixs Astragali and Borneolum Syntheticums (embodiment 1), it is best that its pharmacological effect reaches.
Above-mentioned pharmacological effect experiment also shows; when lacking in Radix Salviae Miltiorrhizae, the Radix Astragali and the Borneolum Syntheticum arbitrary flavor raw material in the prescription of the present invention; its drug effect does not all reach the requirement of purpose of the present invention; especially when lacking Borneolum Syntheticum; its pharmacological effect greatly reduces; therefore; we are surprised to find; being added in of Borneolum Syntheticum improved mice to the tolerance effect of cerebral hypoxia ischemia, cerebral ischemia causes that the protective effect aspect of cerebral edema all is significantly improved to imperfection; this is that those skilled in the art are unpredictable, the resulting beneficial effect of this technical scheme also of the present invention just place.
Toxicology
1. chmice acute toxicity: behind the disposable orally give compound breviscpini of mice capsule 192g crude drug/kg, observed continuously 7, do not see animal toxicity reaction and dead the generation.So compound breviscpini capsule maximum dosage-feeding is 192g crude drug/kg, be about clinical adult and intend 533 times of consumption per day, (it is 0.36g crude drug/kg) that clinical adult intends consumption per day.Compound breviscpini capsule mice LD
50＞192g crude drug/kg.
2. rat long term toxicity: compound breviscpini capsule 24,12, three dosage continuous orals of 6g crude drug/kg, 12 weeks of administration, 26 weeks and 4 weeks of drug withdrawal, male 16 week of Mus administration of performance high dose group the back body weight gains slow down.Each administration group male and female rat urine, defecation, drink water, take the photograph material and general signs and matched group no significant difference; In the routine urianlysis, every index and matched group do not have marked difference; In the hematology measures, rarely seen administration during 26 weeks the female Mus clotting time of high, medium and low dosage group obviously prolong, the no significant difference of each group of 4 weeks of drug withdrawal, this effect points out this medical instrument that certain anticoagulation is arranged, and is not toxic reaction; In the biochemical analysis, the male Mus glutamic oxaloacetic transaminase, GOT of high and low two dosage groups in 12 weeks of compound breviscpini capsule administration is lower than matched group, the creatinine assay of female Mus glutamic oxaloacetic transaminase, GOT of 26 all high dose group and male Mus is lower than matched group, drug withdrawal 4 during week the female Mus glutamic oxaloacetic transaminase, GOT of still visible high dose group measure and be lower than matched group, so do not get rid of this medicine liver function is not had certain influence.All other biochemical indicators are all in normal range; During organ coefficient is checked, the compound breviscpini capsule all is higher than matched group at the coefficient of the administration heart, liver, lung, kidney, prostate and brain of the male Mus of high dose group during 26 weeks, but rarely seen weight of prostate was higher than matched group during the above-mentioned organ weights of the same period was measured, other each organ coefficient of administration group is compared with matched group does not all have significant difference, this kind effect may be slowly relevant with the male Mus body weight gain of high dose group, but it is little that internal organs are increased influence; PATHOMORPHOLOGICAL OBSERVATION OF PULLORUM, rat main organs there is no and be subjected to the relevant pathological change of reagent thing toxicity.So show that compound breviscpini capsule 12g crude drug/kg is a basic security dosage.
In sum, the compound breviscpini capsule has the effect that improves hemorheological property, antithrombotic, improves cerebral ischemia and focal cerebral infarction really, and this prescription is owing to increased Radix Salviae Miltiorrhizae, the Radix Astragali and Borneolum Syntheticum on the basis of Herba Erigerontis, especially the adding of the Radix Astragali and Borneolum Syntheticum, make drug effect significantly better than other compound modes between this four Chinese medicine material (for example lack flavor, lack flavor 1 and 2), this is that those skilled in the art are unpredictable.Its effective dose is that (5-12.5 of 0.36g crude drug/kg) doubly for clinical people's consumption per day in this test in addition, be the mice maximum dosage-feeding (1/107-1/43 of 192g crude drug/kg), illustrating that this medical instrument is equipped with the advantage that toxicity is low, curative effect is high, is safely and effectively for cardiovascular and cerebrovascular disease patient's long-term prescription.
Clinical trial
Adopt the method for randomized controlled to investigate its curative effect and untoward reaction, observe patient's 700 examples altogether, wherein 380 examples are organized in treatment, curative effect cure-remarkable-effectiveness rate 37.87%, total effective rate 86.313%; Matched group 320 examples, cure-remarkable-effectiveness rate 25.56%, 75.13%, two group of apoplexy curative effect of total effective rate is learned processing by statistics, and there is significant difference P＜0.05, and the treatment group is better than matched group.The treatment group is not seen tangible untoward reaction.
Embodiment 1 capsule
Prescription: 5 parts of 653 parts of Borneolum Syntheticums of 653 parts of Radixs Astragali of 1089 parts of Radix Salviae Miltiorrhizaes of Herba Erigerontis
Preparation method:
Get Herba Erigerontis and add 60% alcohol reflux 2 times, each 2 hours, merge extractive liquid,, concentrating under reduced pressure reclaims ethanol to concentrated solution relative density 1.13 (45 ℃), transfer pH6～7 with 10% sodium hydroxide solution, left standstill 24 hours, filter, filtrate is transferred pH2～3 with the dilute sulfuric acid test solution, left standstill 48 hours, and filtered, precipitation washes with water 2 times, standby, filtrate for later use;
Get Radix Salviae Miltiorrhizae and decoct with water 2 times, each 2 hours, medicinal liquid merged, being evaporated to relative density is the clear paste of 1.07～1.10 (65 ℃), places room temperature, stirs to add ethanol down, make ethanol content reach 60%, left standstill 24 hours, filter, it is 1.18 (50 ℃) clear paste that filtrate decompression is concentrated into relative density, transfers pH2～3, merges with Herba Erigerontis filtrate, with water saturation ethyl acetate extraction 4 times, the combined ethyl acetate extract, the reclaim under reduced pressure ethyl acetate is to concentrated solution relative density 1.12 (45 ℃), and is standby;
The Radix Astragali decocts with water 2 times, and each 2 hours, medicinal liquid merged, and filtered, filtrate decompression is concentrated into relative density 1.10 (65 ℃) clear paste, is placed to room temperature, adds ethanol and makes ethanol content reach 60%, leaves standstill 24 hours, filter, filtrate is concentrated into relative density 1.35 (55 ℃) clear paste, and is standby; Precipitation is dissolved in water and puts heating in water bath it is fully dissolved, filtered while hot, and supernatant concentration adds ethanol and makes ethanol content reach 80% to relative density 1.18 (55 ℃).Left standstill 48 hours, and filtered, filtrate discards, and precipitation merges with its alcohol deposit fluid clear paste and together incorporates in Herba Erigerontis precipitation, the ethyl acetate clear paste, put in the vacuum drying oven, drying under reduced pressure is pulverized, and fine powder sieves, add appropriate amount of auxiliary materials and mix, granulate, sneak into the Borneolum Syntheticum fine powder, encapsulated 1000, promptly.After testing, contain lamp-dish flower acetic 5.01mg/ grain in this capsule.
Embodiment 2 soft capsules
Prescription: 8 parts of 549 parts of Borneolum Syntheticums of 453 parts of Radixs Astragali of 1390 parts of Radix Salviae Miltiorrhizaes of Herba Erigerontis
Preparation method: preparation of compositions is with embodiment 1;
The formulation method of soft capsule is made soft capsule routinely.After testing, contain lamp-dish flower acetic 5.68mg/ grain in this capsule.
Embodiment 3 tablets
Prescription: 5 parts of 653 parts of Borneolum Syntheticums of 500 parts of Radixs Astragali of 1089 parts of Radix Salviae Miltiorrhizaes of Herba Erigerontis
Preparation method: preparation of compositions is with embodiment 1;
According to the formulation method of conventional tablet, make tablet.After testing, contain lamp-dish flower acetic 5.20mg/ sheet.
Embodiment 4 granules
Prescription: 6 parts of 894 parts of Borneolum Syntheticums of 600 parts of Radixs Astragali of 900 parts of Radix Salviae Miltiorrhizaes of Herba Erigerontis.
Preparation method: preparation of compositions is with embodiment 1;
According to the formulation method of conventional granulates agent, make granule.After testing, contain lamp-dish flower acetic 1.54mg/g.
Embodiment 5 watered pill
Prescription: 3.5 parts of 800 parts of Borneolum Syntheticums of 453.5 parts of Radixs Astragali of 1447 parts of Radix Salviae Miltiorrhizaes of Herba Erigerontis
Preparation method: preparation of compositions is with embodiment 1;
According to the formulation method of the conventional watered pill, become the watered pill.After testing, contain lamp-dish flower acetic 1.66mg/ ball.
Claims (9)
1, a kind of pharmaceutical composition is made by following materials of weight proportions medicine: Herba Erigerontis 14-29 part, Radix Salviae Miltiorrhizae 1-17 part, Radix Astragali 8-17 part and Borneolum Syntheticum 0.06-0.13 part.
2. the described pharmaceutical composition of claim 1, wherein Herba Erigerontis is that 20-23 part, Radix Salviae Miltiorrhizae are that 8-14 part, the Radix Astragali are that 12-14 part and Borneolum Syntheticum are 0.09-0.11 part.
3. claim 1 or 2 described pharmaceutical compositions, wherein contain:
Herba Erigerontis herb powder, ethanol extract, effective site breviscapine or effective ingredient lamp-dish flower acetic or single, double caffeoylquinic acids; With
The dry root and rhizome powder of Radix Salviae Miltiorrhizae or water are got thing, the total phenolic acid of effective site or effective ingredient such as danshensu, salvianolic acid B, tanshinone; With
The dry root powder of the Radix Astragali or water are got thing or effective site Radix Astragali total glycosides, astragalus polysaccharides or effective ingredient astragaloside; With
Borneolum Syntheticum.
4. the pharmaceutical composition of one of claim 1-3 is granule, hard/soft capsule, tablet, powder, dispersible tablet, oral cavity disintegration tablet, pill, drop pill or oral liquid.
5. the pharmaceutical composition of claim 4 is tablet, pill or hard/soft capsule.。
6. the described medicine of claim 4, wherein said medicine is granule, capsule or tablet.
7. the described preparation of drug combination method of one of claim 1-3 may further comprise the steps:
1) with the Herba Erigerontis alcohol reflux, concentrate, alkali is molten, and acid precipitation filters, and must precipitate and filtrate;
2) Radix Salviae Miltiorrhizae water extraction, ethanol precipitation gets supernatant;
3) concentration step 1) filtrate and step 2) supernatant, merge, use ethyl acetate extraction, obtain the extract clear paste;
4) Radix Astragali water extraction, ethanol precipitation, solution concentration becomes extractum;
5) with borneol powder and step gained 4) extractum, step 3) gained clear paste, step 1) and 4) the gained precipitation merges, mixes.
8. the application of the pharmaceutical composition of one of claim 1-3 in the medicine of preparation treatment apoplexy.
9. the application of claim 9, described medicine is used for the treatment of apoplexy sequela.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102119960A (en) * | 2010-01-07 | 2011-07-13 | 大道隆达（北京）医药科技发展有限公司 | Medicinal composition for activating blood, dissolving stasis, tonifying qi and freeing vessels |
| CN106456688A (en) * | 2014-04-09 | 2017-02-22 | 怀特生技新药股份有限公司 | A composition comprising astragalus membranaceus extract for preventing/treating brain injury and a preparation method thereof |
| CN107137410A (en) * | 2017-06-08 | 2017-09-08 | 中国人民解放军第四军医大学 | A kind of Compound Chinese Herbal Monomer Recipe compatibility agent and preparation method for being used to treat cerebral ischemia |
| CN110680845A (en) * | 2018-07-05 | 2020-01-14 | 北京盈科瑞创新医药股份有限公司 | Pharmaceutical composition for treating stroke and preparation method and application thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1086425A (en) * | 1992-11-05 | 1994-05-11 | 上海中药制药二厂 | Herba asari capsule and preparation method thereof |
| CN1173707C (en) * | 2001-04-23 | 2004-11-03 | 深圳市生物谷科技有限公司 | Medicinal composition containing baicalin and caffoeoylchinic acid |
| CN1194741C (en) * | 2002-12-04 | 2005-03-30 | 云南生物谷灯盏花药业有限公司 | Erigeron breviscapus compound medicament |
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2005
- 2005-01-24 CN CNB2005100026110A patent/CN100435811C/en active Active
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102119960A (en) * | 2010-01-07 | 2011-07-13 | 大道隆达（北京）医药科技发展有限公司 | Medicinal composition for activating blood, dissolving stasis, tonifying qi and freeing vessels |
| CN106456688A (en) * | 2014-04-09 | 2017-02-22 | 怀特生技新药股份有限公司 | A composition comprising astragalus membranaceus extract for preventing/treating brain injury and a preparation method thereof |
| CN107137410A (en) * | 2017-06-08 | 2017-09-08 | 中国人民解放军第四军医大学 | A kind of Compound Chinese Herbal Monomer Recipe compatibility agent and preparation method for being used to treat cerebral ischemia |
| CN110680845A (en) * | 2018-07-05 | 2020-01-14 | 北京盈科瑞创新医药股份有限公司 | Pharmaceutical composition for treating stroke and preparation method and application thereof |
| CN110680845B (en) * | 2018-07-05 | 2022-05-24 | 浙江维康药业股份有限公司 | Pharmaceutical composition for treating stroke and preparation method and application thereof |
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| CN100435811C (en) | 2008-11-26 |
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