CN1931233A - Medicine composition of red sage and epimedium for treating cardiac and cerebral vascular diseases - Google Patents
Medicine composition of red sage and epimedium for treating cardiac and cerebral vascular diseases Download PDFInfo
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- CN1931233A CN1931233A CN 200510044591 CN200510044591A CN1931233A CN 1931233 A CN1931233 A CN 1931233A CN 200510044591 CN200510044591 CN 200510044591 CN 200510044591 A CN200510044591 A CN 200510044591A CN 1931233 A CN1931233 A CN 1931233A
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Abstract
The present invention belongs to the field of medicine technology, and is especially one kind of medicine composition for treating cardiac and cerebral vascular diseases and its preparations and preparation process. The medicine composition is prepared with red sage and epimedium in certain ratio, and may be prepared into different pharmaceutically acceptable forms, preferably injection and orally taken preparation. The medicine composition may be also prepared with red sage extract and epimedium extract. The medicine composition has greatly raised synergistic effect and high stability.
Description
[technical field]
The invention belongs to medical technical field, relate to a kind of Pharmaceutical composition of making by Radix Salviae Miltiorrhizae and Herba Epimedii, and contain preparation of this pharmaceutical composition and preparation method thereof.
[background technology]
Cardiovascular and cerebrovascular disease is known as the No.1 killer who threatens human health always, show that according to relevant investigation report the people that China dies from cardiovascular and cerebrovascular disease every year has more than 300 ten thousand, account for 50% of the annual total death toll of China, and the ill people who survives 75% disability in various degree, 4% is heavy residual.Particularly its morbidity and dead age are rejuvenation trend day by day, and how effectively control also just causes people's great attention.
Cardiovascular and cerebrovascular disease comprises coronary heart disease, angina pectoris, myocardial infarction, blood stasis type pulmonary heart disease, ischemic encephalopathy, cerebral thrombosis, hypertension, hyperlipidemia etc.The main pathogenic factor of these diseases is that arteriosclerosis causes luminal stenosis, pipeline obstruction, thereby causes cerebral ischemia, causes just that head is heavy, dizziness, headache, symptom such as uncomfortable in chest, and severe patient can cause the generation of apoplexy and myocardial infarction.Influence energy metabolism behind the cardiac-cerebral ischemia, multiple variations such as the accumulation of secondary lactic acid, calcium overload, radical damage.Many target spots reverse or improve these and change, and improving comprehensive therapeutic effect is the important goal of Drug therapy.
Radix Salviae Miltiorrhizae is the dry root and rhizome of labiate Radix Salviae Miltiorrhizae; it has many-sided pharmacological action: can increase coronary flow to cardiovascular system; reduce myocardial excitability and conductivity, microcirculation improvement, the formation of antiplatelet gathering and thrombosis; blood viscosity is descended; antioxidation increases oxygen-resistant ability, anti-inflammation; improve renal function, to the cerebral tissue ischemia with in the effects such as protection of perfusion injury.The effective ingredient of Radix Salviae Miltiorrhizae can be divided into fat-soluble and water miscible, and wherein, liposoluble constituent has: Tanshinone I, tanshinone, Tanshinone II B, cryptotanshinone etc.; Water soluble ingredient has: danshensu sodium, protocatechuic acid, protocatechualdehyde, salvianolic acid A, salvianolic acid B, salvianolic acid C etc., and total salvianolic acid is the effective ingredient of Radix Salviae Miltiorrhizae blood circulation promoting and blood stasis dispelling, wherein the effect of salvianolic acid B is the strongest.
Herba Epimedii is the dry aerial parts of Berberidaceae plant Herba Epimedii (EPimedium brevicornum Maxin.), arrow leaf Herba Epimedii (EPimediumsagittatum Maxin.), pubescence Herba Epimedii (EPimedium Pubescens Maxin.), Epimedium wushanense (EPimedium wushanenseT.S.Ying) or Herba Epimedii (EPimedium koreanum Nakai.).Herba Epimedii is used as medicine and starts from Shennong's Herbal, classifies middle product as, has the effect of kidney-replenishing, bone and muscle strengthening, wind-damp dispelling, diseases such as sexual impotence spermatorrhea, dribbling urination, the muscles and bones flaccidity that is usually used in insufficiency of kidney-YANG is soft, anemofrigid-damp arthralgia, numb limbs and tense tendons; Compendium of Material Medica claims it that effect of " beneficial vital essence, hard muscles and bones, by the waist knee joint, heart tonifying power " is arranged.In recent years, for the resources of medicinal plant of comprehensive utilization Epimedium, carried out extensive studies.The modern pharmacology experimentation shows that Herba Epimedii can improve hemorheology, increases the cardiovascular and cerebrovascular vessel blood flow, promote the hemopoietic system function, regulate body's immunity, improve bone metabolism, delay the process of renal failure, strengthen the arrenotoky function, have effects such as defying age, antitumor.The modern chemistry composition Study shows that the main effective ingredient of Herba Epimedii is Herba Epimedii total flavones and epimedium brevicornum polysaccharide.
Herba Epimedii extract is the extract that Herba Epimedii is processed into through extraction, and its main effective ingredient is a Herba Epimedii total flavones, mainly contains icariin and icariside etc.Pharmacological research finds that Herba Epimedii total flavones is that Herba Epimedii promotes immunologic function, participates in bone metabolism, antitumor, the effective ingredient of functions such as enhancing cardiovascular activity.Icariin has coronary blood flow increasing, cerebral blood flow increasing amount, regulates immunity, promotes the synthetic and androgen sample effect of DNA; Can be used for coronary heart disease, climacteric hypertension, sensation of oppression over the chest with shortness of breath and rheumatism etc.
A large amount of pharmacology and clinical researches show that Radix Salviae Miltiorrhizae and Herba Epimedii have good curative effect at aspects such as treatment cardiovascular and cerebrovascular diseases.But, utilize the interaction of Herba Epimedii and Radix Salviae Miltiorrhizae, composition of prescription, the medicine of aspects such as preparation treatment cardiovascular and cerebrovascular disease does not appear in the newspapers as yet.
[summary of the invention]
The purpose of this invention is to provide a kind of medicine for the treatment of cardiovascular and cerebrovascular disease, it is made by following Chinese medicine raw materials by weight proportion: Radix Salviae Miltiorrhizae 60-1000 part Herba Epimedii 30-500 part.Preferably: Radix Salviae Miltiorrhizae 125-500 part Herba Epimedii 60-250 part.Best preferred: 125 parts of 250 parts of Herba Epimedii of Radix Salviae Miltiorrhizae.
More than form,, can make the preparation of 10～100 consumptions,, can be made into 50～100,1～10 of each consumption as injection as if being unit with the gram.As tablet, can be made into 50～100, take 1～10 at every turn.
More than form to be by weight as proportioning, when producing, can or reduce according to the corresponding proportion increase, as large-scale production can be raw material with the kilogram, or be unit with the ton, small-scale production can be unit with the gram also, weight can increase or reduce, but the constant rate of weight proportion between each composition.
The ratio of above weight proportion obtains through science screening, and for especial patient, the ratio of can corresponding adjustment forming increases or reduce being no more than 100%
Radix Salviae Miltiorrhizae and Herba Epimedii respectively or mix through extracting processing and obtain its extract, extract is made various any preparations with the pharmaceutic adjuvant hybrid process again.
Radix Salviae Miltiorrhizae can be carried acid precipitation, alcohol extraction, water extract-alcohol precipitation or water by water and put forward multiple modes such as post and prepare, and the present invention has carried out preferably the extraction process of Radix Salviae Miltiorrhizae, and is as follows:
Get the red rooted salvia coarse powder, decoct with water secondary, add 12 times of amounts of water for the first time, add for the first time 10 times of amounts of water, each 2 hours, collecting decoction, filter, filtrate decompression is concentrated into the concentrated solution of relative density 1.08～1.12, adds ethanol to containing the alcohol amount to 85%, cold preservation 24 hours filters, and filtrate recycling ethanol is to there not being the alcohol flavor, add hydrochloric acid and transfer pH value to 2, extract 3 times with the ethyl acetate jolting, merge ethyl acetate liquid, evaporate to dryness.Residue adds the sour water dissolving of pH value 2, is added on the polyamide column of having handled well, with the water elution of 2 times of column volumes, discards water lotion earlier, and 95% ethanol elution of 4 times of column volumes of reuse is collected eluent, reclaims ethanol, and vacuum drying, promptly.
By the Radix Salviae Miltiorrhizae extract of above-mentioned prepared, yield: 1.5～2% Radix Salviae Miltiorrhizae total phenolic acids content:＞70% content of danshinolic acid B:＞30%.
Herba Epimedii can prepare by mode pharmaceutically commonly used, and the present invention has carried out preferably the extraction process of Herba Epimedii, and is as follows:
Get Herba Epimedii, cut into pieces, decoct with water 2 times, each 1.5 hours, add water was 10 times of amounts at every turn, collecting decoction, cold preservation is placed and is spent the night, and filters, and filtrate is concentrated into the concentrated solution of relative density 1.08～1.10, be added on the polyamide column of having handled well, the water with 3～4 times of column volumes washes 20% alcohol flushing of 2～3 times of column volumes of reuse earlier, discard cleaning mixture, 95% ethanol of 4～5 times of column volumes of reuse carries out eluting, collects eluent, reclaim ethanol, spray drying, promptly.
By the Herba Epimedii extract of above-mentioned prepared, Herba Epimedii total flavones content:＞80%, icariin content:＞15%.
Herba Epimedii can also be by following prepared, but this should be interpreted as Herba Epimedii extract only limits to following preparation technology in the pharmaceutical composition of the present invention.
Technology one: get Herba Epimedii, decoct with water 2 times, each 1.5 hours, add 10 times of amounts of water, merge extractive liquid, filters at every turn, it is 1.08～1.10 concentrated solution that filtrate decompression is concentrated into relative density, adding the petroleum ether jolting, to be extracted into petroleum ether layer colourless, D101 macroporous resin column on the water layer, water, 20% ethanol, 60% ethanol elution successively, collect 60% ethanol elution, concentrating under reduced pressure, spray drying, promptly.By the Herba Epimedii extract of this prepared, Herba Epimedii total flavones content is not less than 60%, and icariin content is not less than 15%.
Technology two: get Herba Epimedii, cut into pieces, add 70% ethanol and decoct 2 times, each 1 hour, add 10 times of amounts of alcohol, merge extractive liquid, at every turn, filter, filtrate recycling ethanol is not to there being the alcohol flavor, and adding the petroleum ether jolting, to be extracted into petroleum ether layer colourless, and water layer adds the ethyl acetate jolting, and to be extracted into ethyl acetate layer colourless, the ethyl acetate layer adds anhydrous sodium sulfate dehydration, concentrating under reduced pressure, spray drying, promptly.By the Herba Epimedii extract of this prepared, Herba Epimedii total flavones content is not less than 50%, and icariin content is not less than 10%.
Technology three: get Herba Epimedii, cut into pieces, add 80% ethanol and decoct 3 times, each 30 minutes, add 8 times of amounts of alcohol, merge extractive liquid, at every turn, filter, filtrate recycling ethanol is not to there being the alcohol flavor, and adding the petroleum ether jolting, to be extracted into petroleum ether layer colourless, and water layer adds the ethyl acetate jolting, and to be extracted into ethyl acetate layer colourless, the ethyl acetate layer adds anhydrous sodium sulfate dehydration, concentrating under reduced pressure, spray drying, promptly.By the Herba Epimedii extract of this prepared, Herba Epimedii total flavones content is not less than 50%, and icariin content is not less than 10%.
Said medicine can be made said dosage form on any pharmaceutics.Optimizing injection and oral formulations commonly used.
Medicine of the present invention can also be made up of a certain proportion of Radix Salviae Miltiorrhizae extract, Herba Epimedii extract, and its weight proportion is: 1: 0.01～20, and optimum ratio: 1: 0.05～10, optimal proportion 1: 0.25～2.Radix Salviae Miltiorrhizae extract wherein can be that water is carried acid precipitation extract, alcohol extract, water extract-alcohol precipitation extract or water and carried column extract, and Radix Salviae Miltiorrhizae extract also can be Radix Salviae Miltiorrhizae total phenolic acids or salvianolic acid B.Radix Salviae Miltiorrhizae extract can utilize the preparation method of prior art to obtain, for example can utilize Chinese patent application CN1352985A, CN1247855A, CN1242364A, CN1384090A, 02117923.9, (Yunnan University of Traditional Chinese Medicine's journal, 2001,24 (4): preparation method 6) obtains Guo Ying etc.Also can grope preparation technology voluntarily obtains.Content of danshinolic acid B is more than 30% in the Radix Salviae Miltiorrhizae extract of the present invention, its total phenolic content more than 50%, be preferably in more than 80%.No matter be or groping preparation technology voluntarily prepares Radix Salviae Miltiorrhizae extract of the present invention,, then should make with extra care, make it to meet above-mentioned content standard if do not reach above-mentioned content standard by prior art.The Herba Epimedii extract can extract by mode pharmaceutically commonly used, as percolation, reflux, extract,, and water extraction, alcohol extraction etc., the main effective ingredient of extract is the Herba Epimedii total flavones, and content is not less than 30%.This medicine can add suitable adjuvant and make acceptable forms on any pharmaceutics.
Another object of the present invention is to provide a kind of medicine for the treatment of cardiovascular and cerebrovascular disease that is used to prepare.Pharmaceutical composition of the present invention can coronary artery dilator, and the alleviating vascular spasm increases coronary flow, improves coronary circulation; Reduce myocardial oxygen consumption, improve the ischemic myocardium contractile function; Can anticoagulant, blood viscosity lowering improves hemorheology and microcirculation; Improve the heart blood supply function, reduce cerebral vascular resistance, increase cerebrovascular flow, improve brain microcirculation; Selectivity retardance β1Shou Ti, decreased heart rate brings high blood pressure down, arrhythmia; Suppress renin-angiotensin system, reduce changes of Catecholamine Content, antiadrenergic drug is risen the sugar effect; Promote the hemopoietic system function, regulate body's immunity, improve bone metabolism, defying age, antitumor etc.Be mainly used in coronary heart disease, angina pectoris, myocardial infarction, blood-deficiency type cardiac insufficiency, ischemic cerebrovascular, and apoplexy and apoplexy sequela, hyperlipidemia etc.
Medicine of the present invention can add one or more pharmaceutically acceptable carriers, with oral, snuffing is gone into or the mode of parenteral is applied to the patient who needs this treatment.Be used for when oral, can be made into conventional solid preparation, as tablet, capsule, soft capsule, dispersible tablet, oral liquid, granule, chewable tablet, oral cavity disintegration tablet, drop pill, slow releasing tablet, slow releasing capsule, controlled release tablet, controlled release capsule, make liquid preparation such as water or oil-suspending agent or other liquid preparation such as syrup etc.; When being used for parenteral, can be made into solution, water or the oil-suspending agent etc. of injection, as liquid drugs injection, freeze-dried powder, aseptic powder injection, transfusion etc.The preferred form of this compositions is injection or oral formulations.
Medicine of the present invention can adopt the conventional method production in the existing pharmaceutical field, can add various pharmaceutically acceptable carriers when needing.Described carrier comprises diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc.
Medicine of the present invention in order to increase its dissolubility, can add solubilizing agents such as tween 80 when making injection.Can add the isoosmotic adjusting agent that is used to regulate osmotic pressure in the transfusion, for example, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium lactate, glucose, xylitol, sorbitol and dextran etc., preferred sodium chloride or glucose.Can add excipient in the powder pin, for example, mannitol, glucose etc.
Medicine of the present invention proves through pharmaceutical research and drug effect animal experiment study result, is the medicine that main component is made by Radix Salviae Miltiorrhizae and Herba Epimedii, can coronary blood flow increasing, increase blood supply of cardiac muscle, reduce left chamber EDP, reduce cardiac preload etc., obviously improve dog blood flow mechanics; Remarkable antiplatelet aggregation; Significantly reduce myocardial infarct size; The rabbit cerebral ischemia reperfusion injury is had significant protective effect remove too much free radical in the body; Protective tissue.Experimental studies results of the present invention proves that Radix Salviae Miltiorrhizae and Herba Epimedii drug combination are synergism, and drug effect obviously strengthens.
The invention has the advantages that: drug combination behind employing Radix Salviae Miltiorrhizae extract and the Herba Epimedii extract reasonable compatibility, prove that through pharmacological experiment drug effect is better than using separately Radix Salviae Miltiorrhizae or Herba Epimedii, drug effect improves.Radix Salviae Miltiorrhizae and Herba Epimedii drug combination are synergism, and dosage reduces relatively, are with a wide range of applications.
Below routine by experiment beneficial effect of further setting forth medicine of the present invention, these experimental examples comprise the pharmacodynamic experiment of pharmaceutical composition of the present invention, the compositions of Radix Salviae Miltiorrhizae extract and Herba Epimedii extract is hereinafter to be referred as the excessive compositions of pellet.Radix Salviae Miltiorrhizae extract in the experimental example comes from embodiment 1, and the Herba Epimedii extract comes from embodiment 2
Experimental example 1: the research of red excessive compositions drug combination drug effect
Animal subject: the Wister rat, male, body weight 200～220g, 10 every group, is divided into 14 groups at random by 140.
Test sample:
Radix Salviae Miltiorrhizae extract group: Radix Salviae Miltiorrhizae extract injection, self-control
Herba Epimedii extract group: Herba Epimedii extract injection, self-control
Red excessive injection (different proportioning) group, 10 groups, self-control
Experimental technique: rat is divided into 14 groups at random: the normal saline matched group; Model group; The Radix Salviae Miltiorrhizae extract group; The Herba Epimedii extract group; Red excessive injection group: red+excessive (1: 0.03,1: 0.05,1: 0.1,1: 0.25,1: 0.5,1: 1,1: 2,1: 6,1: 10,1: 20).Each medicine all is diluted to desired concn with normal saline, the tail vein injection administration.
The rat experiment myocardial infarction model: it is fixing that animal pentobarbital intraperitoneal injection of anesthesia (45mg/kg) is faced upward the position.Tracheal intubation is made the longitudinal incision of 2cm in breastbone left side, nearly breastbone side is cut off the 3rd, the 4th costicartilage, open the thoracic cavity after, connect artificial respirator (ventilation 2ml/100g, 50 times/min).Cut off pericardium, expose heart, left anterior descending coronary artery root threading is in order to ligation, and record standard II lead electrocardiogram was stablized 10 minutes, and the ligation left anterior descending coronary artery is closed the thoracic cavity.With syringe sucking-off animal throat secretions, make animal recover autonomous respiration.Behind the ligation coronary artery 15min, intravenously administrable.Behind the ligation coronary artery 4 hours, win heart, 5 of the following crosscuts of ligature, carry out chlorination nitro blue tetrazolium (N-BT) dyeing, calculating myocardium infarcted region area accounts for the percentage ratio of ventricle and heart area, and carries out statistical procedures (t check).The results are shown in Table 1.
Table 1 compositions is to the influence of rat experiment myocardial inyaretion scope (x ± s)
| Group | Dosage (mg/kg) | Infarcted region/ventricle (%) | Infarcted region/heart (%) |
| The normal saline group | 15 | 30.81±5.35 | 25.14±5.16 |
| Model group | 15 | 34.57±7.85 & | 29.48±5.10 & |
| The Radix Salviae Miltiorrhizae extract group | 15 | 23.58±7.85 * | 19.68±5.45 * |
| The Herba Epimedii extract group | 15 | 24.95±5.62 * | 21.45±4.23 * |
| Red+excessive (1: 0.03) | 15 | 16.08±6.25 **# | 14.09±5.45 **# |
| Red+excessive (1: 0.05) | 15 | 13.56±4.54 **# | 11.45±4.23 **# |
| Red+excessive (1: 0.1) | 15 | 13.25±4.91 **# | 11.31±4.25 **# |
| Red+excessive (1: 0.25) | 15 | 11.87±3.46 **# | 9.78±3.21 **# |
| Red+excessive (1: 0.5) | 15 | 11.15±3.48 **# | 9.21±2.83 **# |
| Red+excessive (1: 1) | 15 | 11.45±2.42 **# | 9.62±2.48 **# |
| Red+excessive (1: 2) | 15 | 12.05±5.41 **# | 10.01±4.25 **# |
| Red+excessive (1: 6) | 15 | 13.02±5.54 **# | 11.03±5.23 **# |
| Red+excessive (1: 10) | 15 | 14.58±3.24 **# | 12.75±3.84 **# |
| Red+excessive (1: 20) | 15 | 15.04±3.81 **# | 12.95±3.41 **# |
Annotate:
*P＜0.05,
*P＜0.01 is compared with model group;
#P＜0.05 is compared with Radix Salviae Miltiorrhizae extract group or Herba Epimedii extract group;
﹠amp;P＜0.05, model group is compared with the normal saline group.
Conclusion: model group compares with the normal saline group that there were significant differences, illustrate the modeling success (
﹠amp;P＜0.05).Each administration group all have tangible function of resisting myocardial ischemia (
*P＜0.05 He
*P＜0.01), wherein the effect of each proportioning of Radix Salviae Miltiorrhizae extract and Herba Epimedii extract compatibility (1: 0.03～20) be better than single with Radix Salviae Miltiorrhizae extract or Herba Epimedii extract (
#P＜0.05), point out two medicine compatibilities that synergistic function is arranged; In 1: 0.25～2 scopes, effect is more remarkable
Experimental example 2: red excessive compositions antiplatelet aggregative activity
Laboratory animal: the Wister rat, male, body weight 200～220g, 10 every group, is divided into 7 groups at random by 70.
Test sample: Radix Salviae Miltiorrhizae extract group: Radix Salviae Miltiorrhizae extract injection, self-control
Herba Epimedii extract group: Herba Epimedii extract injection, self-control
Red excessive composite injection (various dose proportioning) group, 4 groups, self-control
Experimental technique: rat is divided into 7 groups at random, 10 every group, is respectively the normal saline matched group; The Radix Salviae Miltiorrhizae extract group; The Herba Epimedii extract group; Red excessive composite injection (pellet+excessive=100mg+25mg; Pellet+excessive=50mg+25mg; Pellet+excessive=50mg+50mg; Red+excessive=as 25mg+50mg) to organize.Each treated animal administration, once a day, successive administration 7 days, after the last administration 1 hour, from abdominal aortic blood, anticoagulant adopted 3.28% sodium citrate after the Animal Anesthesia, with blood with 1: 9 mixed.With anticoagulated whole blood 1500r.min under 20 ℃ of conditions
-1Centrifugal 5min obtains platelet rich plasma (PPR).After leaving and taking quantitative PPR, will remain PPR once more with 3000r.min
-1Centrifugal 10min obtains the rich or poor platelet blood plasma of own control (PPP).Regulate PPR concentration with PPP, make each PPR concentration identical.In 37 ℃ constant temperature hole after the preheating, (final concentration is 3 μ mol.L to add ADP with PPR
-1) cause and write down maximum agglutination rate by platelet aggregation.The results are shown in Table 2.
Table 2 antiplatelet aggregative activity (X ± SD)
| Group | Dosage (mg/kg) | Maximum agglutination rate | The P value |
| The normal saline matched group | 15 | 86.65±18.46 | - |
| The Radix Salviae Miltiorrhizae extract group | 15 | 71.58±16.27 | ＜0.05 |
| The Herba Epimedii extract group | 15 | 68.47±16.78 | ＜0.05 |
| Pellet+excessive=100mg+25mg | 15 | 61.05±16.25 | ＜0.01 |
| Pellet+excessive=50mg+25mg | 15 | 60.14±15.85 | ＜0.01 |
| Pellet+excessive=50mg+50mg | 15 | 61.54±16.48 | ＜0.01 |
| Pellet+excessive=25mg+50mg | 15 | 61.78±15.38 | ＜0.01 |
Annotate: compare P＜0.05 with Radix Salviae Miltiorrhizae extract group or Herba Epimedii extract group for red excessive group
Conclusion: each administration group is anticoagulant (P＜0.05 and P＜0.01) obviously, wherein the effect of red excessive composite injection is better than single with Radix Salviae Miltiorrhizae extract or Herba Epimedii extract (P＜0.05), the compositions of proof Radix Salviae Miltiorrhizae extract and Herba Epimedii extract compatibility has good antiplatelet aggregative activity, and relevant with the dosage ratio of compositions, red+excessive=during 50mg+25mg effect the strongest.
Experimental example 3: red excessive composite injection intravenously administrable is to the hemodynamic influence of anesthetized open-chest dog
Laboratory animal: the hybrid dog, 35, body weight is at 11.0～13.0 kilograms, 5 every group.
Test sample:
Radix Salviae Miltiorrhizae extract group: Radix Salviae Miltiorrhizae extract injection, self-control
Herba Epimedii extract group: Herba Epimedii extract injection, self-control
Red excessive composite injection (various dose proportioning) group, 4 groups, self-control
Dosage: 20mg/kg
Experimental technique: get 35 hybrid dogs, body weight is at 11.0～13.0 kilograms, and 5 every group, the male and female dual-purpose is divided into 7 groups at random, is respectively the normal saline matched group; The Radix Salviae Miltiorrhizae extract group; The Herba Epimedii extract group; Red excessive composite injection (pellet+excessive=100mg+25mg; Pellet+excessive=50mg+25mg; Pellet+excessive=50mg+50mg; Red+excessive=as 25mg+50mg) to organize.
Dog is anaesthetized with 3% pentobarbital sodium 1ml/kg forelimb intravenous injection, and dorsal position is fixed on the operating-table, cuts off the hair of cervical region, chest and right hind inboard.75% ethanol disinfection cropping district.Separate trachea, and insert tracheal intubation, be equipped with the artificial respiration and use; Separate external jugular vein, and enter right atrium and reach auricular sious through superior vena cava, be used to extract the blood of Coronary vein from the external jugular vein intubate; Separate femoral vein, insert venous cannulation, slow constant speed is injected 10% glucose in the whole experiment.Separate femoral artery, insert arterial cannulation (being full of the heparin sodium normal saline of 25U/ml in the pipe), connect TP-400T type pressure transducer, by AP-641G type blood pressure amplifier recording blood pressure (systolic pressure SAP, diastolic pressure DAP, mean arterial pressure MAP).Under the artificial respiration, open breast, cut off pericardium, separate root of ascending aorta and ramus descendens anterior arteriae coronariae sinistrae in the 4th intercostal, place respectively suitable internal diameter the electromagnetic blood flowmeter probe (13,2mm) measure cardiac output (CO) and coronary artery blood flow (CBF).With left ventricular cannulation (being full of the heparin-saline of 25U/ml in the pipe) in the left ventricle apex is inserted left ventricle, by TP-400T type pressure transducer, by AP-641G type blood pressure amplifier record left indoor pressure (LVP), write down left chamber EDP (LVEDP) by AD-601G type amplifier: it is subcutaneous that needle electrode is inserted the dog extremity, traces standard I I lead electrocardiogram (ECG).Above-mentioned measuring-signal is all imported RM-6000 type eight road physiology monitor records, traces.The biomedical biosignal processing system of the signal of telecommunication of cardiac output, electrocardio, blood pressure and intraventricular pressure being imported microcomputer is handled simultaneously, and reads intraventricular pressure peak value (LVSP), EDP (LVEDP), ventricular systole parameter (+dP/dt by microcomputer
Max), ventricular diastole parameter (dP/dt
Max).At last, calculate parameters (TPVR) such as cardiac index (CI), stroke volume (SV), SI (SI), every stroke work index (SWI), blood vessel total peripheral resistance.Stablize 20min after operation is finished, medicine is dissolved in the 100ml normal saline, splash into through the femoral vein constant speed in the 15min.
1h, 2h extract left ventricle and crown venous blood respectively before administration, after the administration, and anticoagulant heparin is injected among the i-STAT G3+Cartridges (G3+ of i-STAT company type test pieces), measure the artery and vein blood oxygen pressure by blood gas analyzer.Myocardial oxygen consumption is calculated by the Kanter formula, and its formula is: MVO
2=3.25 * 10 * CF (PaO
2-PvO
2)/Wt.MVO
2Be meant the oxygen consumption of chamber, every 100g left side cardiac muscle, CF is a coronary flow, PaO
2, PvO
2Represent the artery and vein blood oxygen pressure respectively, Wt is that left compartment muscle is heavy.
All data are all represented with meansigma methods ± standard deviation, according to the variation of each index in each group of medication front and back, adopt pairing t-to check and judge the statistical significance that the various indexs in medication front and back change.
Experimental result: (1) is to the influence of the total peripheral vascular resistance of anesthetized dog: with matched group relatively, the red excessive composite injection group of each proportioning all can significantly reduce the total peripheral vascular resistance of anesthetized dog (P＜0.01), the Herba Epimedii extract group can obviously reduce the total peripheral vascular resistance of anesthetized dog (P＜0.05), and the effect of Radix Salviae Miltiorrhizae extract group is than Herba Epimedii extract injection group low (P＜0.05).
(2) to the influence of chamber, anesthetized dog left side EDP: with matched group relatively, the red excessive composite injection group of each proportioning all can significantly reduce anesthetized dog left side chamber EDP (P＜0.01), and Radix Salviae Miltiorrhizae extract group and Herba Epimedii extract injection group can obviously reduce anesthetized dog left side chamber EDP (P＜0.05).
(3) to the influence of anesthetized dog coronary artery blood flow: with matched group relatively, the red excessive composite injection group of each proportioning all can significantly increase anesthetized dog coronary artery blood flow (P＜0.01), and Radix Salviae Miltiorrhizae extract group and Herba Epimedii extract injection group can obviously increase anesthetized dog coronary artery blood flow (P＜0.05).
(4) to the influence of anesthetized dog ventricular systole parameter: with matched group relatively, the red excessive composite injection group of each proportioning all can significantly increase anesthetized dog ventricular systole parameter (P＜0.01), and Radix Salviae Miltiorrhizae extract group and Herba Epimedii extract injection group can obviously increase anesthetized dog ventricular systole parameter (P＜0.05).
(5) to the influence of anesthetized dog ventricular diastole parameter: with matched group relatively, the red excessive composite injection group of each proportioning all can significantly increase anesthetized dog ventricular diastole parameter (P＜0.01), and Radix Salviae Miltiorrhizae extract group and Herba Epimedii extract injection group can obviously increase anesthetized dog ventricular diastole parameter (P＜0.05).
(6) to the influence of anesthetized dog cardiac output, stroke volume, cardiac index and SI: with matched group relatively, the red excessive composite injection group of each proportioning all can significantly increase cardiac output, stroke volume, cardiac index, the SI (P＜0.01) of anesthetized dog, and Radix Salviae Miltiorrhizae extract group and Herba Epimedii extract injection group can obviously increase cardiac output, stroke volume, cardiac index, the SI (P＜0.05) of anesthetized dog.
Conclusion: Radix Salviae Miltiorrhizae extract and Herba Epimedii extract drug combination can pass through coronary blood flow increasing, the blood supply of cardiac muscle is increased, reduce left chamber EDP, make blood be easy to flow to the endocardium lower area, coronary artery blood flow is redistributed from visceral pericardium; Can obviously reduce cardiac preload, afterload is not had obvious influence; Can significantly improve the blood-pumping function of heart; Can obviously improve the contraction and the diastolic function of heart.The effect of Radix Salviae Miltiorrhizae extract and Herba Epimedii extract drug combination is better than the effect of Radix Salviae Miltiorrhizae extract or the independent medication of Herba Epimedii extract, points out two medicines that synergistic function is arranged.
Experimental example 4: red excessive compositions is to the protective effect of rabbit cerebral ischemia perfusion injury
Laboratory animal: rabbit, 132, the male and female dual-purpose, body weight 2.4～2.8kg is divided at random: ischemia-reperfusion group (18), the different proportioning groups (18 every group) of red excessive composite injection, salvia miltiorrhiza extract for treating group (18), Herba Epimedii extract injection for treating group (18) and Sham-operated control group (6).
Test sample:
Radix Salviae Miltiorrhizae extract group: Radix Salviae Miltiorrhizae extract injection, self-control
Herba Epimedii extract group: Herba Epimedii extract injection, self-control
Red excessive composite injection (various dose proportioning) group, 4 groups of (pellet+excessive=100mg+25mg; Pellet+excessive=50mg+25mg; Pellet+excessive=50mg+50mg; Red+excessive=25mg+50mg), self-control
The preparation of test liquid: all test samples all are made into the test liquid of 15mg/ml
Dosage: 15mg/kg
Experimental technique: (1) ischemia-reperfusion group: 18, urethane lipoprotein solution 1g/kg auricular vein anesthesia with 25%, the cervical region median incision separates trachea and inserts tracheal casing pipe, expose bilateral carotid, folder closes both sides tremulous pulse 20min, cause cerebral ischemia, pour into 1,6 and 12h respectively again, each 6 of 3 time points.Behind the pine folder 10min, auricular vein is injected normal saline 5ml/kg.(2) red excessive composite injection treatment group: the red excessive composite injection of each proportioning is a group greatly, totally 4 groups greatly, 18 of every big groups, the same ischemia-reperfusion group of operation method, each 6 of 3 time points.Behind the pine folder 10min, auricular vein is injected red excessive composite injection 15mg/kg.(3) salvia miltiorrhiza extract for treating group: 18, the same ischemia-reperfusion group of operation method, each 6 of 3 time points.Behind the pine folder 10min, auricular vein is injected Radix Salviae Miltiorrhizae extract test liquid 15mg/kg.(4) Herba Epimedii extract injection for treating group: 18, the same ischemia-reperfusion group of operation method, each 6 of 3 time points.Behind the pine folder 10min, auricular vein is injected Herba Epimedii extract injection 15mg/kg.(5) Sham-operated control group: 6, only row anesthesia and tremulous pulse exclusion and not pressing from both sides closed, and puts to death behind the 1h.Above-mentioned each group promptly breaks end after testing and finishing, and strips out brain in ice bath, separates on the ice pan and cuts bilateral hippocampus tissue, is placed in 4 ℃ of refrigerators with the tinfoil parcel to store, and surveys phospholipase A fully
2(PLA
2); Cut cortical tissue and survey brain infarction area, brain water content, the E Ding district tissue specimen of choosing middle cerebral artery blood supply district carries out pathological observation.All measurement data data all adopt meansigma methods ± standard deviation to represent, relatively adopt the t check between group.
Experimental result: (1) is to hippocampal tissue PLA
2Active influence: after ischemia-reperfusion group is poured into 1h, 6h and 12h again, PLA
2Activity obviously increases (P＜0.01) than Sham-operated control group, and prolongs PLA with infusion time
2The activity trend that tapers off, but comparing difference not significantly (P＞0.05) between each time point; Red excessive composite injection treatment group (1h, 6h, the 12h) PLA of each proportioning
2Active obviously reduction relatively has significant difference (P＜0.01) with Sham-operated control group and each corresponding time point of ischemia-reperfusion group, and with irritating time lengthening, PLA again
2Activity is recovered normal level gradually; Salvia miltiorrhiza extract for treating group and Herba Epimedii extract injection for treating group (1h, 6h, 12h) PLA
2The active reduction relatively has notable difference (P＜0.05) with Sham-operated control group and each corresponding time point of ischemia-reperfusion group, and the effect of Radix Salviae Miltiorrhizae extract is lower than the Herba Epimedii extract injection.
(2) to the influence of cortical tissue's water content (%) and infarct size (%): each time point brain water content of ischemia-reperfusion group all increases; The red excessive composite injection treatment of each proportioning is organized each time point brain water content and is compared obviously with ischemia-reperfusion group and alleviate (P＜0.001), and brain infarction area is compared obviously with ischemia-reperfusion group and dwindled (P＜0.01); The salvia miltiorrhiza extract for treating group is compared obvious reduction (P＜0.01) with each time point brain water content of Herba Epimedii extract injection for treating group with ischemia-reperfusion group, brain infarction area is compared obviously with ischemia-reperfusion group and dwindled (P＜0.05, P＜0.01).
(3) brain tissue pathology change: Sham-operated control group does not have the infarction shape, and the neuronal structure form is normal, continuously the matter edema; Ischemia-reperfusion group has the infarction shape, the neuron swelling of infarction shape week, and cell outline is unclear, and interstitial edema is obvious; The red excessive composite injection treatment group of each proportioning, salvia miltiorrhiza extract for treating group, Herba Epimedii extract injection for treating group infarction shape area all dwindle, and the neuron swelling of infarction shape week is not obvious, and interstitial edema obviously alleviates; Red excessive composite injection treatment group effect is more obvious.
Conclusion: above-mentioned experimental result shows that behind the cerebral ischemia re-pouring, red excessive composite injection, Radix Salviae Miltiorrhizae extract, Herba Epimedii extract injection all can reduce hippocampal tissue PLA
2Activity, improve due to the cerebral ischemia in the environment disorder, alleviate cerebral edema, reduce brain infarction area; Illustrate that red excessive compositions, Radix Salviae Miltiorrhizae extract, Herba Epimedii extract all have the removing free radical, the fast shut-off free radical chain reactions suppresses lipid peroxidation, alleviates cerebral tissue protective effects such as delayed cerebral injury.The red excessive composite injection of each proportioning drug effect in every index all is higher than the effect of Radix Salviae Miltiorrhizae extract and the independent medication of Herba Epimedii extract injection, points out two medical instruments that synergistic function is arranged.
Experimental example 5: red excessive compositions is to the influence of hyperlipidemia rats lipid metabolism
Laboratory animal: rat, 50, body weight 200～220g is divided into 5 groups at random, 10 every group.
Test sample:
Radix Salviae Miltiorrhizae extract group: Radix Salviae Miltiorrhizae extract injection, self-control.
Herba Epimedii extract group: Herba Epimedii extract injection, self-control.
Red excessive composite injection group (red+excessive=as 50mg+25mg), to be divided into basic, normal, high 3 dosage groups, self-control.
Experimental technique: rat is divided into normal feedstuff group at random, high lipid food group, the basic, normal, high dosage group of the red excessive compositions of injection; Single cage is raised, and freely ingests and drinks water.Normal feedstuff group feed normal feedstuff; The Adeps Sus domestica of high lipid food group interpolation 10% on normal feedstuff prescription basis and 2% cholesterol and 1% gallbladder salt; The basic, normal, high dosage group of the red excessive compositions of injection is replenished the red excessive compositions of injection respectively on the high lipid food basis, the content that makes the red excessive compositions of injection of replenishing in the feedstuff is 1,2,3g/kg.Nutritional intervention is after 4 weeks, and femoral vein is got the variation that blood is observed every analysis indexes.Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and HDL-C (HDL-C) are measured with biotinylation kit.Atherogenic index (AI) is calculated with formula AI=LDL-C/HDL-C.Experimental data is represented with meansigma methods ± standard deviation, carries out one factor analysis of variance.
Experimental result: high lipid food group Serum TC, TG, LDL-C, HDL-C and AI are significantly higher than normal feedstuff group (P＜0.05, P＜0.01), but the amplitude (215%) that LDL-C raises is much larger than HDL-C (25%), and it mainly is because due to the LDL-C rising that the Serum TC that visible high lipid food group causes raises.The red excessive compositions intervention groups Serum TC of injection, TG, LDL-C and AI all significantly are lower than high lipid food group (P＜0.01, P＜0.001), but the red excessive compositions low dosage rat blood serum HDL-C of injection reduces to normal feedstuff group level, middle and high dosage group HDL-C level significantly raise (P＜0.05).
Conclusion: this experiment is intervened high fat rat with the red excessive compositions of the injection of various dose, experimental result shows, the red excessive compositions of intervention groups injection all can effectively reduce the value of high lipid diet Serum TC, TG, LDL-C level and AI, and is the most remarkable with the effect of high dose group; Illustrate that Herba Epimedii extract and Radix Salviae Miltiorrhizae extract drug combination have good effect for reducing blood fat, HDL-C in the blood that can significantly raise simultaneously, atherosis (AS) will play better action to prevention of arterial.
Experimental example 6: red excessive composite injection stability experiment
Sample: red excessive composite injection (self-control, red+excessive=50mg+25mg)
Investigation project: character, pH value, clarity
Long-time stability experimental technique and result: this product is put under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% and placed 6 months, 12 months, every index has no significant change, experimental result show composite injection long-term place basicly stable.
[specific embodiment]
Come further to set forth preparation of drug combination method of the present invention by the following examples.Following embodiment can make those skilled in the art more fully understand the present invention, but does not limit the present invention in any way.The used Radix Salviae Miltiorrhizae extract of embodiment 4-12 comes from embodiment 1, and the Herba Epimedii extract comes from embodiment 2, and red excessive extract comes from embodiment 3.
The preparation of embodiment 1 Radix Salviae Miltiorrhizae extract
1. extraction process by water screening experiment
Amount of water, extraction time and extraction time are bigger to the influence of extracting the result, are index with Radix Salviae Miltiorrhizae total phenolic acids content and yield of extract therefore, investigate three kinds of factors to extracting result's influence with orthogonal experiment method.Factor and level design see Table 3.
Table 3 Radix Salviae Miltiorrhizae alcohol extraction process is investigated the factor level table
| Level/factor | A amount of water (doubly) | B extraction time (hour) | C extraction time (inferior) |
| 1 | 18 | 3 | 1 |
| 2 | 20 | 4 | 2 |
| 3 | 22 | 5 | 3 |
Experimental technique takes by weighing Radix Salviae Miltiorrhizae 100g, and totally 9 parts, extract by the requirement of each row of table 3 number, merge extractive liquid, filters, and filtrate concentrates and is settled to 500ml, and is standby.
The assay of Radix Salviae Miltiorrhizae total phenolic acids
The preparation precision of reference substance solution takes by weighing exsiccant protocatechualdehyde reference substance 1mg, is dissolved in water, and is settled to 100ml.
The preparation precision of need testing solution is measured sample solution 25ml, put in the 50ml volumetric flask, thin up to scale precision is measured 0.1ml and is put and add ethanol 5ml in the 25ml volumetric flask, adds 0.3% sodium lauryl sulphate 2ml, 0.6% potassium ferricyanide, one 0.9% ferric oxide (face and use preceding mixed in equal amounts) 1ml, so 5min is placed in the dark place, add the 0.1mol/L hydrochloric acid solution to scale, shake up, after 20min is placed in the dark place, put in the lena colorimetric pool, the 720nm place measures.
The algoscopy colorimetry
The mensuration precision of yield of extract is measured each sample solution 25ml, puts in the evaporating dish of constant weight, and behind water bath method, 105 ℃ of dryings 3 hours, cooling was 30 minutes in the dislocation exsiccator, accurately rapidly claims to decide weight.Calculate yield of extract.The results are shown in Table 4.
Table 4 Radix Salviae Miltiorrhizae extraction process by water is investigated orthogonal design table
| Sequence number | Factor | Total phenolic acid (%) | Yield of extract (%) | |||
| A | B | C | D | |||
| 1 | 1 | 1 | 1 | 1 | 0.572 | 15.12 |
| 2 | 1 | 2 | 2 | 2 | 0.631 | 16.23 |
| 3 | 1 | 3 | 3 | 3 | 0.569 | 16.78 |
| 4 | 2 | 1 | 2 | 3 | 0.763 | 18.32 |
| 5 | 2 | 2 | 3 | 1 | 0.656 | 18.09 |
| 6 | 2 | 3 | 1 | 2 | 0.737 | 17.67 |
| 7 | 3 | 1 | 3 | 2 | 0.761 | 19.11 |
| 8 | 3 | 2 | 1 | 3 | 0.802 | 18.42 |
| 9 | 3 | 3 | 2 | 1 | 0.823 | 19.84 |
| K 1 | 1.772 | 2.096 | 2.111 | 2.051 | ||
| K 2 | 2.156 | 2.089 | 2.217 | 2.129 | ||
| K 3 | 2.386 | 2.129 | 1.986 | 2.134 | ||
| R | 0.614 | 0.043 | 0.231 | 0.083 | ||
Table 5 Radix Salviae Miltiorrhizae extraction process analysis of variance table
| Factor | Sum of sguares of deviation from mean | Degree of freedom | Inequality | The F value | Significance |
| A | 0.06415 | 2 | 0.032 | 44.549 | P＜0.05 |
| B | 0.0003 | 2 | 0.000 | 0.208 | |
| C | 0.00891 | 2 | 0.00446 | 6.188 | |
| D (error term) | 0.00144 | 2 | 0.00024 |
F
0.05(2，2)＝19.00 F
0.05(2，2)＝99.00
By table 4, table 5 result as can be seen, amount of water is to influence the principal element that Radix Salviae Miltiorrhizae extracts, and extraction time and extraction time are little to its influence, in conjunction with commercial production, with reference to yield of extract, determine that the Radix Salviae Miltiorrhizae extraction process is A
3B
3C
2, that is: get Radix Salviae Miltiorrhizae, decocting with water twice, twice all is 2 hours, adds 12 times of amounts of water for the first time, adds 10 times of amounts of water for the second time.
2. the investigation of alcohol precipitation process
The investigation of alcohol precipitation concentration:
Experimental technique takes by weighing Radix Salviae Miltiorrhizae 200g, totally 3 parts, decocts with water respectively twice, 1.5 hours for the first time, add 12 times of amounts of water, 1 hour for the second time, add 10 times of amounts of water, merge extractive liquid, filters, it is 1.17～1.20 (80 ℃) that filtrate is concentrated into relative density, uses Ethanol Treatment 2 times, and containing amount of alcohol in the solution for the first time is 75%, for the second time be respectively 80%, 85%, 90%, each all cold preservation is placed, and filters, reclaim ethanol, concentrate and be settled to 1000ml.Precision is measured 50ml, according to 1 following assay and yield of extract assay method, measures the content and the yield of extract of total phenolic acid.Experimental result sees Table 6.
Table 6 alcohol precipitation concentration is investigated experimental result
| Alcohol precipitation concentration (%) | Total phenolic content (%) | Yield of extract (%) |
| 80 | 0.737％ | 9.49 |
| 85 | 0.779％ | 6.55 |
| 90 | 0.798％ | 4.97 |
By table 6 result as can be seen, when alcohol precipitation concentration is 85%, can guarantee the content of total phenolic acid, can reach the purpose of remove impurity again, therefore selecting ethanol precipitation twice concentration is 85%.
The Radix Salviae Miltiorrhizae extract identification experiment:
Get this product 0.2g, porphyrize adds 70% methanol 25ml, and reflux 1 hour filters, and filtrate evaporate to dryness, residue add 70% methanol 1ml makes dissolving, as need testing solution.Other gets the salvianolic acid B reference substance, adds 70% methanol and makes the solution that every 1ml contains 2mg, in contrast product solution.Use tlc determination, draw above-mentioned two kinds of each 5ul of solution, put in same silica gel G F respectively
254On the lamellae, be developing solvent, launch, take out, dry, put under the ultra-violet lamp (254nm) and inspect with toluene-chloroform-ethyl acetate-methanol-formic acid (2: 3: 4: 0.5: 2).
In the test sample chromatograph, with reference substance chromatograph relevant position on, show the speckle of same color.
The experiment of Radix Salviae Miltiorrhizae extract assay:
Total phenolic content is measured colorimetry
The preparation precision of reference substance solution takes by weighing the protocatechualdehyde reference substance 1mg that is dried to constant weight in 105 ℃, is dissolved in water, and is settled to 100ml.
The preparation precision of need testing solution takes by weighing sample 50mg, put in the 50ml volumetric flask, thin up to scale precision is measured 0.1ml and is put and add ethanol 5ml in the 25ml volumetric flask, adds 0.3% sodium lauryl sulphate 2ml, 0.6% potassium ferricyanide, one 0.9% ferric oxide (face and use preceding mixed in equal amounts) 1ml, so 5min is placed in the dark place, add the 0.1mol/L hydrochloric acid solution to scale, shake up, after 20min is placed in the dark place, put in the lena colorimetric pool, the 720nm place measures.
The assay high performance liquid chromatography of salvianolic acid B
Chromatographic condition and system suitability experiment are filler with the octadecylsilane chemically bonded silica; With methanol-acetonitrile-formic acid-water (30: 10: 1: 59) be mobile phase; The detection wavelength is 286nm.Theoretical cam curve is calculated by the danshensu peak should be not less than 1500.
It is an amount of that the preparation precision of reference substance solution takes by weighing the salvianolic acid B reference substance, adds 75% methanol and make the solution that every 1ml contains 0.14mg, promptly.
The about 0.2g of this product is got in the preparation of need testing solution, and accurate the title decides, and puts in the tool plug conical flask, and the accurate 75% methanol 50ml that adds claims to decide weight, reflux 1h takes out, and puts coldly, claims to decide weight again, supplies with 75% methanol to subtract weight loss, shake up, filter, get subsequent filtrate, promptly.
Accurate respectively reference substance solution and each 20ul of need testing solution of drawing of algoscopy injects chromatograph of liquid, measures, promptly.
According to above-mentioned selection process, get red rooted salvia coarse powder 100kg, decoct with water secondary, add for the first time 12 times of amounts of water, add 10 times of amounts of water, each 2 hours for the first time, collecting decoction filters, and filtrate decompression is concentrated into the concentrated solution of relative density 1.08～1.12, add ethanol to containing the alcohol amount to 85%, cold preservation 24 hours filters, filtrate recycling ethanol adds hydrochloric acid and transfers pH value to 2 to there not being the alcohol flavor, extracts 3 times with the ethyl acetate jolting, merge ethyl acetate liquid, evaporate to dryness.Residue adds the sour water dissolving of pH value 2, is added on the polyamide column of having handled well, with the water elution of 2 times of column volumes, discards water lotion earlier, and 95% ethanol elution of 4 times of column volumes of reuse is collected eluent, reclaims ethanol, and vacuum drying, gets Radix Salviae Miltiorrhizae extract.
3 batches of water-soluble extract of red sage root that make according to the method described above, wherein total phenolic acid and content of danshinolic acid B measurement result see Table 7.As can be seen from the results, the yield of the Radix Salviae Miltiorrhizae extract that this method obtains is: 1.5～2%, and Radix Salviae Miltiorrhizae total phenolic acids content:＞70%, content of danshinolic acid B:＞45%.
The assay result and the yield of table 7 Radix Salviae Miltiorrhizae extract
| Batch | Radix Salviae Miltiorrhizae extract (kg) | Total phenolic content (%) | Content of danshinolic acid B (%) |
| 1 | 1.78 | 75.11 | 51 |
| 2 | 1.85 | 80.85 | 54 |
| 3 | 1.94 | 70.27 | 48 |
Experiment of embodiment 2 Herba Epimedii extract craft screenings and preparation
Amount of water, extraction time, extraction time are bigger to the influence of extracting the result, are index with icariin and general flavone content therefore, investigate four kinds of factors to extracting result's influence with orthogonal experiment method.Factor and level design see Table 8.
Table 8 Herba Epimedii extraction process by water is investigated the factor level table
| Level/factor | A amount of water (doubly) | B extraction time (inferior) | C extraction time (hour) |
| 1 | 16 | 1 | 2 |
| 2 | 18 | 2 | 3 |
| 3 | 20 | 3 | 4 |
Experimental technique takes by weighing Herba Epimedii 100g, and totally 9 parts, extract by the requirement of each row of table 8 number, merge extractive liquid, filters, and filtrate concentrates and is settled to 1000ml, and is standby.
The assay of Herba Epimedii total flavones
The algoscopy precision is measured above-mentioned solution 1ml, puts in the 10ml volumetric flask, adds 70% ethanol dilution to scale, shakes up, as need testing solution.Other gets the icariin reference substance, adds 70% ethanol and makes the solution that every 1ml contains 10 μ g, in contrast product solution.Getting need testing solution and reference substance solution respectively, is blank with the corresponding reagent, detects according to spectrophotography, measures absorbance at 270nm wavelength place, calculates, promptly.The results are shown in Table 9.
Content Determination of Icariin is measured
Detect according to high performance liquid chromatography.
Chromatographic condition and system suitability experiment are filler with the octadecyl silane; With second eyeball-water (30: 70) is mobile phase; The detection wavelength is 270nm.Theoretical cam curve is calculated by the icariin peak and is not less than 1500.
Reference substance solution must prepare precision, and to take by weighing the icariin reference substance an amount of, adds methanol and make the solution that every 1ml contains 0.1mg, promptly.
The preparation precision of need testing solution is measured each sample liquid 2ml, puts in the 25ml measuring bottle, adds 70% methanol and is diluted to scale, shakes up, promptly.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.The results are shown in Table 9.
Table 9 Herba Epimedii extraction process is investigated orthogonal design table
| Sequence number | Factor | General flavone content (%) | Icariin (%) | ||||
| A | B | C | D | ||||
| 1 | 1 | 1 | 1 | 1 | 3.23 | 0.396 | |
| 2 | 1 | 2 | 2 | 2 | 3.91 | 0.452 | |
| 3 | 1 | 3 | 3 | 3 | 3.14 | 0.381 | |
| 4 | 2 | 1 | 2 | 3 | 3.09 | 0.372 | |
| 5 | 2 | 2 | 3 | 1 | 3.67 | 0.425 | |
| 6 | 2 | 3 | 1 | 2 | 3.31 | 0.401 | |
| 7 | 3 | 1 | 3 | 2 | 3.07 | 0.352 | |
| 8 | 3 | 2 | 1 | 3 | 3.48 | 0.431 | |
| 9 | 3 | 3 | 2 | 1 | 3.81 | 0.447 | |
| Total flavones | K 1 | 10.28 | 9.37 | 10.02 | 10.71 | ||
| K 2 | 10.07 | 11.06 | 10.81 | 10.29 | |||
| K 3 | 10.36 | 10.26 | 9.88 | 9.71 | |||
| R | 0.29 | 1.69 | 0.93 | 1.00 | |||
| Icariin | K 1 | 1.229 | 1.12 | 1.228 | 1.268 | ||
| K 2 | 1.198 | 1.308 | 1.271 | 2.753 | |||
| K 3 | 1.23 | 1.229 | 1.158 | 1.184 | |||
| R | 0.031 | 0.188 | 0.113 | 0.084 | |||
Table 10 Herba Epimedii total flavones analysis of variance table
| Soruces of variation | Sum of sguares of deviation from mean | Degree of freedom | Variance | The F value |
| A | 0.015 | 2 | 0.00748 | 0.089 |
| B | 0.340 | 2 | 0.170 | 2.023 |
| C | 0.168 | 2 | 0.0838 | 0.997 |
| D (error term) | 0.168 | 2 | 0.0840 |
Table 11 icariin analysis of variance table
| Soruces of variation | Sum of sguares of deviation from mean | Degree of freedom | Variance | The F value |
| A | 0.000221 | 2 | 0.00011 | 0.173 |
| B | 0.005941 | 2 | 0.00297 | 4.663 |
| C | 0.002169 | 2 | 0.00108 | 1.702 |
| D (error term) | 0.001274 | 2 | 0.00064 |
By the result of table 9, table 10, table 11 as can be seen, the descending factor of Herba Epimedii total flavones extraction effect influence is followed successively by B＞C＞A,, determines that the Herba Epimedii extraction process is A in conjunction with industrial practical situation
3B
2C
2, that is: get Herba Epimedii, decoct with water twice, each 1.5 hours, add 10 times of amounts of water at every turn.
Because having relatively high expectations of injection, so on the basis of above-mentioned selection process, make with extra care again.Concrete technology is as follows:
Get Herba Epimedii 100kg, cut into pieces, decoct with water 2 times, each 1.5 hours, add water was 10 times of amounts at every turn, collecting decoction, cold preservation is placed and is spent the night, and filters, and filtrate is concentrated into the concentrated solution of relative density 1.08～1.10, be added on the polyamide column of having handled well, the water with 3～4 times of column volumes washes 20% alcohol flushing of 2～3 times of column volumes of reuse earlier, discard cleaning mixture, 95% ethanol of 4～5 times of column volumes of reuse carries out eluting, collects eluent, reclaim ethanol, spray drying, promptly.
By above-mentioned prepared 3 batch samples, check as follows:
The Herba Epimedii extract identification experiment:
Get Herba Epimedii extract 0.1g, add ethanol 10ml, warm macerating 30 minutes filters, and filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.It is an amount of that other gets the icariin reference substance, adds methanol and make the solution that every 1ml contains 0.1mg, in contrast product solution.The thin layer chromatography experiment, draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel H lamellae of adhesive with the sodium carboxymethyl cellulose, with ethyl acetate-butanone-formic acid-water (10: 1: 1: 1) as developing solvent, launch, take out, airing is put under the ultra-violet lamp (365nm) and is inspected.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the kermesinus speckle of same color; Spray is put under the ultra-violet lamp (365nm) again and is inspected with the aluminum chloride test solution, shows identical fluorescent red-orange speckle.
The experiment of Herba Epimedii extract assay:
(1) assay of Herba Epimedii total flavones
The algoscopy precision takes by weighing Herba Epimedii extract 0.01g, puts in the 50ml measuring bottle, adds methanol 25ml supersound process 30 minutes, adds methanol and is diluted to scale, shakes up, and filters, as need testing solution.Other gets the icariin reference substance, adds methanol and makes the solution that every 1ml contains 10 μ g, in contrast product solution.Getting need testing solution and reference substance solution respectively, is blank with the corresponding reagent, according to spectrophotography, measures absorbance at 270nm wavelength place, calculates, promptly.
(2) content Determination of Icariin is measured
Detect according to high performance liquid chromatography.
Chromatographic condition and system suitability experiment are filler with the octadecyl silane; With second eyeball-water (30: 70) is mobile phase; The detection wavelength is 270nm.Theoretical cam curve is calculated by the icariin peak and is not less than 1500.
Reference substance solution must prepare precision, and to take by weighing the icariin reference substance an amount of, adds methanol and make the solution that every 1ml contains 0.1mg, promptly.
The preparation precision of need testing solution is measured each sample liquid 2ml, puts in the 25ml measuring bottle, adds 70% methanol and is diluted to scale, shakes up, promptly.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
3 batch sample assays the results are shown in Table 12.The result shows, by the Herba Epimedii extract of this prepared, and yield: 2-3%, Herba Epimedii total flavones content is not less than 80%, and icariin content is not less than 15%.
The assay result and the yield of table 12 Herba Epimedii extract
| Batch | General flavone content (%) | Icariin content (%) | Yield (%) |
| 1 | 82.12 | 17.56 | 2.67 |
| 2 | 83.23 | 18.05 | 2.34 |
| 3 | 82.35 | 17.72 | 2.45 |
Embodiment 3: the preparation of Radix Salviae Miltiorrhizae extract and Herba Epimedii extract
1000 times by the clinical prescription amount take by weighing raw material:
Radix Salviae Miltiorrhizae 2.5kg Herba Epimedii 1.25kg
Preparation method is as follows:
(a) get the red rooted salvia coarse powder of recipe quantity, decoct with water secondary, add 12 times of amounts of water for the first time, add for the second time 10 times of amounts of water, each 2 hours, collecting decoction, filter, filtrate decompression is concentrated into the concentrated solution of relative density 1.08～1.12, adds ethanol to containing the alcohol amount to 85%, cold preservation 24 hours filters, and filtrate recycling ethanol is to there not being the alcohol flavor, add hydrochloric acid and transfer pH value to 2, extract 3 times with the ethyl acetate jolting, merge ethyl acetate liquid, evaporate to dryness.Residue adds the sour water dissolving of pH value 2, is added on the polyamide column of having handled well, with the water elution of 2 times of column volumes, discards water lotion earlier, and 95% ethanol elution of 4 times of column volumes of reuse is collected eluent, reclaims ethanol, and vacuum drying, gets Radix Salviae Miltiorrhizae extract.Yield: 1.77% Radix Salviae Miltiorrhizae total phenolic acids content: 76% content of danshinolic acid B: 40%.
(b) get the Herba Epimedii of recipe quantity, cut into pieces, decoct with water 2 times, each 1.5 hours, add water was 10 times of amounts at every turn, collecting decoction, cold preservation is placed and is spent the night, filter, filtrate is concentrated into the concentrated solution of relative density 1.08～1.10, is added on the polyamide column of having handled well, water with 3～4 times of column volumes washes earlier, 20% alcohol flushing of 2～3 times of column volumes of reuse discards cleaning mixture, and 95% ethanol of 4～5 times of column volumes of reuse carries out eluting, collect eluent, reclaim ethanol, spray drying promptly gets Herba Epimedii extract.Herba Epimedii total flavones content: 83%, icariin content: 25%.
(c) with above-mentioned Radix Salviae Miltiorrhizae extract and Herba Epimedii extract mixture and, be called for short red excessive extract, promptly get the effective ingredient of medicine of the present invention, can add suitable adjuvant and make various dosage forms.
Embodiment 4: the preparation of red excessive composition powder injection
Prescription 1:
Radix Salviae Miltiorrhizae extract 100g
Herba Epimedii extract 25g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
Prescription 2:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 25g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
Prescription 3:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 50g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
Prescription 4:
Radix Salviae Miltiorrhizae extract 25g
Herba Epimedii extract 50g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
Prescription 5:
Red excessive extract 100g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
Preparation technology:
1) vessel of at first dosing being used and antibiotic glass bottle, plug etc. carry out aseptic process.
2) take by weighing supplementary material according to recipe quantity.
3) heating for dissolving in Herba Epimedii extract and Radix Salviae Miltiorrhizae extract (or red excessive extract) adding dosing amount 50% sterile water for injection is complete.It is complete that mannitol adds the sterile water for injection heated and stirred dissolving of dosing amount 30%, merges above-mentioned solution, adds sterile water for injection to full dose.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.22um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) be sub-packed in the antibiotic glass bottle half tamponade.Sample is put into the freeze dryer lyophilization.Pre-freeze-45 ℃ 5 hours, low-temperature vacuum drying-45 ℃～0 ℃ 20 hours was warming up to 25 ℃ of vacuum dryings 3 hours then.
9) lyophilizing finishes, and lid is rolled in tamponade.
10) finished product is examined entirely, the packing warehouse-in.
Embodiment 5: the preparation of red excessive compositions aqueous injection
Prescription 1:
Radix Salviae Miltiorrhizae extract 100g
Herba Epimedii extract 25g
Water for injection adds to 1000ml
Prepare 1000 altogether
Prescription 2:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 25g
Water for injection adds to 1000ml
Prepare 1000 altogether
Prescription 3:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 50g
Water for injection adds to 1000ml
Prepare 1000 altogether
Prescription 4:
Radix Salviae Miltiorrhizae extract 25g
Herba Epimedii extract 50g
Water for injection adds to 1000ml
Prepare 1000 altogether
Prescription 5:
Red excessive extract 100g
Water for injection adds to 1000ml
Prepare 1000 altogether
Preparation technology:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) with heated and stirred dissolving in the water for injection of Radix Salviae Miltiorrhizae extract and Herba Epimedii extract (or red excessive extract) adding dosing amount 80% fully.
3) benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.45um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) with the solution sealing by fusing in glass ampule.
9) 100 ℃ of flowing steam sterilizations are 30 minutes.
10) while hot sample being put into 0.01% methylene blue solution hunts leak.
11) lamp inspection, finished product is examined entirely, the packing warehouse-in.
Embodiment 6: the preparation of red excessive compositions transfusion
The sodium chloride transfusion:
Prescription 1:
Radix Salviae Miltiorrhizae extract 100g
Herba Epimedii extract 25g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 2:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 25g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 3:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 50g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 4:
Radix Salviae Miltiorrhizae extract 25g
Herba Epimedii extract 50g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 5:
Red excessive extract 100g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Preparation technology:
1) handles the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) Herba Epimedii extract, Radix Salviae Miltiorrhizae extract (or red excessive extract) are added the dissolving of dosing amount 40% water for injection heated and stirred fully, sodium chloride is complete with the water for injection dissolving of dosing amount 20%.
3) merge above-mentioned solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.45um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) fill is in the infusion bottle of 100ml.
9) 115 ℃ of pressure sterilizings are 30 minutes.
10) lamp inspection, finished product is examined entirely, the packing warehouse-in.
Glucose infusion liquid:
Prescription 1:
Radix Salviae Miltiorrhizae extract 100g
Herba Epimedii extract 25g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 2:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 25g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 3:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 50g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 4:
Radix Salviae Miltiorrhizae extract 25g
Herba Epimedii extract 50g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 5:
Red excessive extract 100g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Preparation technology:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) with heated and stirred dissolving in Herba Epimedii extract, Radix Salviae Miltiorrhizae extract (or red excessive extract) adding dosing amount 20% water for injection fully, that glucose is complete with the water for injection dissolving of dosing amount 20%, heated and boiled 15 minutes.
3) merge above-mentioned solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.45um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) fill is in the infusion bottle of 100ml.
9) 115 ℃ of pressure sterilizings are 30 minutes.
10) lamp inspection, finished product is examined entirely, the packing warehouse-in.
Embodiment 7: the preparation of red excessive composition tablet
Prescription 1:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 25g
Starch 40.0g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6.0g
Carboxymethylstach sodium 12.0g
Prepare 1000 altogether
Prescription 2:
Red excessive extract 100g
Starch 40.0g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6.0g
Carboxymethylstach sodium 12.0g
Prepare 1000 altogether
Preparation technology:
1) it is standby Herba Epimedii extract and Radix Salviae Miltiorrhizae extract (or red excessive extract) to be pulverized 100 mesh sieves.
2) take by weighing supplementary material according to recipe quantity.
3) hypromellose 2% the aqueous solution made soluble in water is standby.
4) with Herba Epimedii extract, Radix Salviae Miltiorrhizae extract, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is dried under 60 ℃ condition.
7) dry good granule adds magnesium stearate and carboxymethylstach sodium, crosses 18 mesh sieve granulate, mix homogeneously.
8) sampling, the semi-finished product chemical examination.
9) the sheet weight sheet of determining according to chemical examination.
10) finished product is examined entirely, the packing warehouse-in.
Embodiment 8: the preparation of red excessive composition capsule
Prescription 1:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 25g
Starch 20.0g
Microcrystalline Cellulose 60.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6.0g
Prepare 1000 altogether
Prescription 2:
Red excessive extract 100g
Starch 20.0g
Microcrystalline Cellulose 60.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6.0g
Prepare 1000 altogether
Preparation technology:
1) it is standby Herba Epimedii extract and Radix Salviae Miltiorrhizae extract (or red excessive extract) to be pulverized 100 sieves.
2) take by weighing supplementary material according to recipe quantity.
3) hypromellose 2% the aqueous solution made soluble in water is standby.
4) with Herba Epimedii extract, Radix Salviae Miltiorrhizae extract, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is dried under 60 ℃ condition.
7) dry good granule adds magnesium stearate, crosses 18 mesh sieve granulate, mix homogeneously.
8) sampling, the semi-finished product chemical examination.
9) loading amount of determining according to chemical examination incapsulates.
10) finished product is examined entirely, the packing warehouse-in.
Embodiment 9: the preparation of red excessive composition granule
Prescription 1:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 25g
Icing Sugar 2000.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription 2:
Red excessive extract 100g
Icing Sugar 2000.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Preparation technology:
1) it is standby sucrose to be pulverized 100 mesh sieves.It is standby that Herba Epimedii extract and Radix Salviae Miltiorrhizae extract (or red excessive extract) were pulverized 100 mesh sieves.
2) take by weighing supplementary material according to recipe quantity.
3) the method mix homogeneously that Herba Epimedii extract, Radix Salviae Miltiorrhizae extract and Icing Sugar are progressively increased with equivalent, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and makes suitable soft material,
4) cross 20 mesh sieve system granules.
5) granule is dried under 60 ℃ condition.
6) dried granule is crossed 18 mesh sieve granulate.
7) sampling, the content of principal agent is determined loading amount in the semi-finished product chemical examination granule.
8) packing, finished product is examined entirely, the packing warehouse-in.
Embodiment 10: the preparation of red excessive composition dripping agent
Prescription 1:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 25g
Polyethylene glycol 6000 1000g
Prescription 2:
Red excessive extract 100g
Polyethylene glycol 6000 1000g
Preparation technology:
Pulverized behind 100 mesh sieves Herba Epimedii extract and Radix Salviae Miltiorrhizae extract (or red excessive extract) standby.With polyethylene glycol 6000 heating and melting in water-bath, treat to add after whole fusions Herba Epimedii extract and Radix Salviae Miltiorrhizae extract (or red excessive extract), stirring and dissolving, 60 mesh sieves filter, and keep 60 ℃ to splash in the liquid paraffin that is chilled to below 10 ℃ and make ball.
Embodiment 11: the preparation of red excessive composition soft
Prescription 1:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 25g
Soybean oil 1000.0g
Soybean phospholipid 500g
Cera Flava 500g
Prepare 1000 altogether
Prescription 2:
Red excessive extract 100g
Soybean oil 1000.0g
Soybean phospholipid 500g
Cera Flava 500g
Prepare 1000 altogether
Preparation technology:
With the soybean oil of recipe quantity and soybean phospholipid, Cera Flava heating and melting, mixing is put coldly, adds the Herba Epimedii extract, Radix Salviae Miltiorrhizae extract (or red excessive extract) grinds well, and is pressed into soft capsule and gets final product.
Embodiment 12: the preparation of red excessive composition oral liquid
Prescription 1:
Radix Salviae Miltiorrhizae extract 50g
Herba Epimedii extract 25g
Sodium benzoate 15g
Stevioside 10g
Purified water adds to 10000ml
Prepare 1000 altogether
Prescription 2:
Red excessive extract 100g
Sodium benzoate 15g
Stevioside 10g
Purified water adds to 10000ml
Prepare 1000 altogether
Preparation technology:
1) with heated and stirred dissolving in the purified water of Herba Epimedii extract, Radix Salviae Miltiorrhizae extract (or red excessive extract) adding dosing amount 50% fully.
2) sodium benzoate and stevioside is complete with the water dissolution of dosing amount 20%.
3) merge above-mentioned solution, add purified water to full dose.
4) filtering with microporous membrane of mistake 0.8um.
5) semi-finished product chemical examination.
6) fill.Finished product is examined entirely, the packing warehouse-in.
Claims (10)
1. a medicine for the treatment of cardiovascular and cerebrovascular disease is characterized in that, is made by following Chinese medicine raw materials by weight proportion:
Radix Salviae Miltiorrhizae 60-1000 part Herba Epimedii 30-500 part.
2. medicine according to claim 1 is characterized in that, is made by following Chinese medicine raw materials by weight proportion:
Radix Salviae Miltiorrhizae 125-500 part Herba Epimedii 60-250 part.
3. medicine according to claim 2 is characterized in that, is made by following Chinese medicine raw materials by weight proportion:
125 parts of 250 parts of Herba Epimedii of Radix Salviae Miltiorrhizae.
4. according to the described arbitrary medicine of claim 1-3, it is characterized in that described Radix Salviae Miltiorrhizae and Herba Epimedii respectively or mix through extracting processing and obtain its extract, extract is made various any preparations with the pharmaceutic adjuvant hybrid process again.
5. medicine according to claim 4 is characterized in that the extraction process of Radix Salviae Miltiorrhizae wherein may further comprise the steps:
A) get red rooted salvia, pulverize, decoct with water, filter, merging filtrate concentrates;
B) precipitate with ethanol filters, and filtrate is transferred pH value;
C) extraction, jolting are extracted, and the extracting solution evaporate to dryness gets Radix Salviae Miltiorrhizae extract A;
The extraction process of Herba Epimedii may further comprise the steps:
A) get epimedium herb, section decocts with water, and filters, and gets filtrate;
B) filtrate concentrates, and drying gets the Herba Epimedii extract A.
6. according to the described medicine of claim 5, it is characterized in that Radix Salviae Miltiorrhizae extract A can also be further refining, step is: with Radix Salviae Miltiorrhizae extract A dissolving, last polyamide column separates, and water and ethanol elution are collected eluent successively, and vacuum drying gets Radix Salviae Miltiorrhizae extract B;
Herba Epimedii extract A can also be further refining, and step is: after Herba Epimedii extract A is dissolved in water, be added on the polyamide column of having handled well, water and ethanol is eluting respectively, collects eluent, reclaims ethanol, and spray drying gets Herba Epimedii extract B.
7. according to the described arbitrary medicine of claim 1-3, it is characterized in that this medicine can make said dosage form on any pharmaceutics.
8. medicine according to claim 1, it is characterized in that this medicine can also be made by Radix Salviae Miltiorrhizae extract, Herba Epimedii extract, its weight proportion is: 1: 0.01～20, and the main effective ingredient of Radix Salviae Miltiorrhizae extract wherein is Radix Salviae Miltiorrhizae total phenolic acids or salvianolic acid B, content is not less than 30%; The main effective ingredient of Herba Epimedii extract wherein is the Herba Epimedii total flavones, and content is not less than 30%.
9. medicine according to claim 8 is characterized in that the weight proportion of Radix Salviae Miltiorrhizae extract and Herba Epimedii extract is: 1: 0.05～10, and the main effective ingredient of Radix Salviae Miltiorrhizae extract wherein is Radix Salviae Miltiorrhizae total phenolic acids or salvianolic acid B, content is not less than 30%; The main effective ingredient of Herba Epimedii extract wherein is the Herba Epimedii total flavones, and content is not less than 30%.
10. described medicine according to Claim 8-9 is characterized in that this medicine can make said dosage form on any pharmaceutics.
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|---|---|---|---|
| CN2005100445913A CN1931233B (en) | 2005-09-14 | 2005-09-14 | Medicine composition of red sage and epimedium for treating cardiac and cerebral vascular diseases |
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|---|---|---|---|
| CN2005100445913A CN1931233B (en) | 2005-09-14 | 2005-09-14 | Medicine composition of red sage and epimedium for treating cardiac and cerebral vascular diseases |
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| CN1931233B CN1931233B (en) | 2011-03-23 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108887535A (en) * | 2018-06-20 | 2018-11-27 | 天马（安徽）国药科技股份有限公司 | A kind of health beverages and preparation method thereof that restoring consciouness is allayed excitement |
| CN111544465A (en) * | 2020-06-08 | 2020-08-18 | 上海市同济医院 | Traditional Chinese medicine composition for secondary prevention after PCI (peripheral component interconnect) operation of acute coronary syndrome |
| CN112089786A (en) * | 2020-10-19 | 2020-12-18 | 琛蓝(美国)营养制品股份有限公司 | Multifunctional traditional Chinese medicine compound composition and application thereof in pharmaceutical preparation |
| CN115804453A (en) * | 2022-12-20 | 2023-03-17 | 吉林大学 | Epimedium lipid-lowering tablet and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1255125C (en) * | 2003-07-02 | 2006-05-10 | 广东医学院 | Chinese medicine formulation with functions of resisting senescence and preventing and treating posteoporosis and cerebral lesion |
| CN1739606A (en) * | 2005-08-26 | 2006-03-01 | 江苏省药物研究所 | Active extract composition of epimedium and red sage and its medicinal use |
-
2005
- 2005-09-14 CN CN2005100445913A patent/CN1931233B/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108887535A (en) * | 2018-06-20 | 2018-11-27 | 天马（安徽）国药科技股份有限公司 | A kind of health beverages and preparation method thereof that restoring consciouness is allayed excitement |
| CN111544465A (en) * | 2020-06-08 | 2020-08-18 | 上海市同济医院 | Traditional Chinese medicine composition for secondary prevention after PCI (peripheral component interconnect) operation of acute coronary syndrome |
| CN112089786A (en) * | 2020-10-19 | 2020-12-18 | 琛蓝(美国)营养制品股份有限公司 | Multifunctional traditional Chinese medicine compound composition and application thereof in pharmaceutical preparation |
| WO2022082485A1 (en) * | 2020-10-19 | 2022-04-28 | 琛蓝(美国)营养制品股份有限公司 | Traditional chinese medicine compound composition having multiple effects and application thereof in pharmaceutical preparation |
| CN115804453A (en) * | 2022-12-20 | 2023-03-17 | 吉林大学 | Epimedium lipid-lowering tablet and preparation method thereof |
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| Publication number | Publication date |
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| CN1931233B (en) | 2011-03-23 |
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