CN101161268B - Pharmaceutical composition of red sage root and cattail pollen - Google Patents
Pharmaceutical composition of red sage root and cattail pollen Download PDFInfo
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- CN101161268B CN101161268B CN2006100692775A CN200610069277A CN101161268B CN 101161268 B CN101161268 B CN 101161268B CN 2006100692775 A CN2006100692775 A CN 2006100692775A CN 200610069277 A CN200610069277 A CN 200610069277A CN 101161268 B CN101161268 B CN 101161268B
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Abstract
The present invention relates to medical technique field, to provide a medicinal composition for treating cardiovascular and cerebrovascular diseases, its preparation method and preparation containing the medicinal composition, constitution of the raw materials used for preparing the medicinal composition containing the effective components are red sage root or red sage root extraction and cattail pollen or cattail pollen extraction. The medicinal composition can be prepared into clinic or pharmaceutical acceptable preparations, optimizing oral preparation or injection. Mainly used for preparing medicine for treating cardiovascular and cerebrovascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, blood stasis type pulmonary heart disease, ischemic encephalopathy, cerebral thrombus, hypertension, hyperlipemia and etc. The medicinal composition of the present invention has synergistic interaction, effect is increased greatly than using single red sage root or red sage root extraction and single cattail pollen or cattail pollen extraction, low toxicity, high safety, and good stability.
Description
[technical field]
The invention belongs to medical technical field, relate to pharmaceutical composition of Radix Salviae Miltiorrhizae or Radix Salviae Miltiorrhizae extract and Pollen Typhae or Pollen Tyjphae extract and preparation method thereof, the application in the medicine of preparation treatment cardiovascular and cerebrovascular disease and contain the preparation of this pharmaceutical composition.
[background technology]
Cardiovascular and cerebrovascular disease all is the formidable enemy who threatens human health all the time, seizes 1,200 ten thousand people's life every year, near 1/4 of the total death of population.Along with China progresses into aged society, and change along with expanding economy and life style, dietary habit, the prevalence of cardiovascular and cerebrovascular disease and mortality rate rise just year by year, predict according to World Health Organization (WHO), to the year two thousand twenty, noninfectious will account for 79% of China's cause of death, and wherein cardiovascular and cerebrovascular disease will account for the first place.Therefore, how effectively to prevent and treat the great attention that cardiovascular and cerebrovascular disease also just causes people.
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 Salvia miltiorrhiza Bge, bitter in the mouth, cold nature, Gui Xin, Liver Channel.Stasis-dispelling and pain-killing is arranged, promoting blood circulation to restore menstrual flow, the effect of the relieving restlessness that clears away heart-fire.Be used for menoxenia, amenorrhea dysmenorrhea ， lumps in the chest and abdomen, breast ventral spine pain, pyretic arthralgia pain, skin infection swells and ache, dysphoria and insomnia, hepatosplenomegaly, angina pectoris.
Radix Salviae Miltiorrhizae 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 makes blood viscosity descend antioxidation; increase oxygen-resistant ability; anti-inflammation improves renal function, to the effects such as protection of cerebral tissue ischemia and reperfusion 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.Total salvianolic acid is the effective ingredient of Radix Salviae Miltiorrhizae blood circulation promoting and blood stasis dispelling, and wherein the effect of salvianolic acid B is the strongest.
Pollen Typhae is the dry pollen of the turbid Herba Typhae Typha of Typhaceae vegetation water angustifolia L, typha orientalis Typha orientalis Presl or congener.Behind the clip male flower, dry, become the pollen that has male flower, be POLLEN TYPHAE CUM STAMEN.Pollen Typhae also can be made Pollen Tyjphae or Pollen Typhae carbon through the process of preparing Chinese medicine.Sweet in the mouth, property is flat, returns liver, pericardium channel.Hemostasis is arranged, blood stasis dispelling, treating stranguria effect.Be used for spitting blood epistaxis, spitting of blood, metrorrhagia, traumatic hemorrhage, amenorrhea dysmenorrhea, gastral cavity ventral spine pain, tumbling and swelling, blood strangury and dry pain.
Pollen Typhae mainly contains steroid class, flavonoid, alkyl compound, acid ingredient, aminoacid, inorganic constituents etc., the pharmacological action of relevant Pollen Typhae report is a lot of in recent years, especially aspect cardiovascular, has microcirculation improvement, reduce the effect of serum cholesterol, atherosclerosis, can be used for cardiovascular disease such as coronary heart disease, angina pectoris, myocardial infarction, hyperlipidemia, hypertension, wherein flavone compound is its main effective ingredient aspect cardiovascular.
At present, utilize the interaction of Radix Salviae Miltiorrhizae or Radix Salviae Miltiorrhizae extract and Pollen Typhae or Pollen Tyjphae extract, 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]
One of purpose of the present invention provides a kind of being used to and prepares the compositions for the treatment of cardiovascular and cerebrovascular diseases medicament, and make the contained raw materials of effective components medicine of this pharmaceutical composition and be: Radix Salviae Miltiorrhizae, Pollen Typhae perhaps are: Radix Salviae Miltiorrhizae extract, Pollen Tyjphae extract.
Make the consisting of of crude drug of the contained active ingredient of this pharmaceutical composition: 200～4000 parts of Radix Salviae Miltiorrhizaes, 1000～10000 parts of Pollen Typhaes, a large amount of screening experiment through the inventor prove that pharmaceutical composition of the present invention all has the effect of Synergistic in above-mentioned weight portion scope; Be preferably: 500～2000 parts of Radix Salviae Miltiorrhizaes, 2000～5000 parts of Pollen Typhaes; More preferably: 1000 parts of Radix Salviae Miltiorrhizaes, 3000 parts of Pollen Typhaes.
In the aforementioned pharmaceutical compositions, Radix Salviae Miltiorrhizae and Pollen Typhae can be with The suitable solvent respectively or mix through extracting processing and obtain its extract, and extract is made various any preparations with the pharmaceutic adjuvant hybrid process again.Described solvent is meant solvent pharmaceutically commonly used, preferred water or alcohol, and extracting method can extract with pharmaceutically conventional method, as infusion process, percolation, decocting method, reflux extraction, continuous extraction etc.The effective ingredient of gained total extract is mainly phenolic acids and flavone compound.
Radix Salviae Miltiorrhizae in the aforementioned pharmaceutical compositions 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 step is as follows:
Get red rooted salvia, be ground into coarse powder, decoct with water twice, add for the first time 12 times of amounts of water, add 10 times of amounts of water, each 2 hours for the second time, collecting decoction filters, and filtrate decompression is concentrated into the concentrated solution of relative density 1.10～1.15 (60 ℃), add ethanol and reach 85% to containing the alcohol amount, cold preservation 24 hours filters, filtrate recycling ethanol adds hydrochloric acid adjust pH 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, promptly.
By the Radix Salviae Miltiorrhizae extract of above-mentioned prepared, yield is 1.5～2%, and Radix Salviae Miltiorrhizae total phenolic acids content is not less than 70%, and wherein the content of salvianolic acid B is not less than 30%.
Pollen Typhae in the aforementioned pharmaceutical compositions can be put on multiple modes such as post, alcohol extraction, alcohol extraction upper prop and prepare by water extract-alcohol precipitation, water, the present invention has carried out preferably the extraction process of Pollen Typhae, and step is as follows:
Get cattail pollen, add 70% ethanol extraction three times, extracted 3 hours at every turn.First and second time adds 14 times of amounts of alcohol, adds 10 times of amounts of alcohol for the third time.Merge extractive liquid,, filter, filtrate recycling ethanol to relative density is the concentrated solution of 1.04～1.06 (50 ℃), adds to wait water gaging to dilute, mixing, 4 ℃ of cold preservation 24 hours, centrifugal, get supernatant, extract 2 times with the jolting of equivalent petroleum ether, discard petroleum ether liquid, water liquid extracts 3 times with the jolting of equivalent water-saturated n-butanol, merges n-butanol extracting liquid, be concentrated into dried, residue adds low amounts of water makes dissolving, last AB-8 macroporous resin column, water, 35% ethanol, 70% ethanol elution respectively, collect 70% ethanol elution, reclaim ethanol, drying under reduced pressure, promptly.
By the Pollen Tyjphae extract of above-mentioned prepared, yield is 2～4%, and content of flavonoids is not less than 50%.
Pollen Typhae can also be extracted preparation by following method, but be not limited only to following method except that being adopted the said method extraction:
Technology one: get cattail pollen, decoct with water three times, first, second time is each to decoct 3 hours, added 12 times of amounts of water, decocted for the third time 2 hours.Add 10 times of amounts of water.Merge extractive liquid, filters, and filtrate is concentrated into the clear paste that relative density is 1.10～1.15 (60 ℃), adds ethanol to content and reaches 80%, stirs evenly, and placement is spent the night, and filters, and filtrate recycling ethanol is evaporated to the thick paste shape to there not being the alcohol flavor, vacuum drying, promptly.
By the Pollen Tyjphae extract of above-mentioned prepared, yield is 10～20%, and content of flavonoids is not less than 30%.
Technology two: get cattail pollen, decoct with water three times, first, second time is each to decoct 3 hours, added 12 times of amounts of water, decocted for the third time 2 hours.10 times of amounts of amount of water.Merge extractive liquid, filters, and filtrate is concentrated into the clear paste that relative density is 1.10～1.15 (60 ℃), add ethanol to content and reach 80%, placement is spent the night, and filters, filtrate recycling ethanol to relative density is the concentrated solution of 1.04～1.06 (60 ℃), the water gaging dilution such as add after, extract 2 times with the jolting of equivalent petroleum ether, discard petroleum ether liquid, water liquid extracts 3 times with the jolting of equivalent water-saturated n-butanol, merges n-butanol extracting liquid, is concentrated into the thick paste shape, spray drying, promptly.
By the Pollen Tyjphae extract of above-mentioned prepared, yield is 5～10%, and content of flavonoids is not less than 50%.
Technology three: get cattail pollen, add 70% ethanol extraction three times, extracted 3 hours at every turn.First and second time adds 14 times of amounts of alcohol, adds 10 times of amounts of alcohol for the third time.Merge extractive liquid, filters, and filtrate recycling ethanol to relative density is the clear paste of 1.04～1.06 (50 ℃), the water gaging dilution such as add, mixing, 4 ℃ of cold preservation 24 hours, centrifugal, get supernatant, extract 2 times with the jolting of equivalent petroleum ether, discard petroleum ether liquid, water liquid extracts 3 times with the jolting of equivalent water-saturated n-butanol, merges n-butanol extracting liquid, is concentrated into the thick paste shape, spray drying, promptly.
By the Pollen Tyjphae extract of above-mentioned prepared, yield is 3～9%, and content of flavonoids is not less than 50%.
Technology four: get cattail pollen, decoct with water three times, first, second time is each to decoct 3 hours, added 12 times of amounts of water, decocted for the third time 2 hours.10 times of amounts of amount of water.Merge extractive liquid, filters, and filtrate is concentrated into the clear paste that relative density is 1.10～1.15 (60 ℃), add ethanol to content and reach 80%, stir evenly, placement is spent the night, filter, filtrate recycling ethanol to relative density is the concentrated solution of 1.04～1.06 (60 ℃), the water gaging dilution such as add after, extract 2 times with the jolting of equivalent petroleum ether, discard petroleum ether liquid, water liquid extracts 3 times with the jolting of equivalent water-saturated n-butanol, merges n-butanol extracting liquid, is concentrated into dried, residue adds low amounts of water makes dissolving, last macroporous resin column with the water elution of 1 times of column volume, discards water lotion earlier, 35% ethanol elution of 2 times of volumes of reuse, discard 35% ethanol elution, use 70% ethanol elution of 3 times of column volumes then, collect 70% ethanol elution, decompression recycling ethanol, be concentrated into the thick paste shape, spray drying, promptly.
By the Pollen Tyjphae extract of above-mentioned prepared, yield is 1～5%, and content of flavonoids is not less than 50%.
Pharmaceutical composition of the present invention can also be made by Radix Salviae Miltiorrhizae extract and Pollen Tyjphae extract, calculate with respect to the yield of medical material according to extract that (yield of Radix Salviae Miltiorrhizae extract is 1.5%～2.0%, the yield of Pollen Tyjphae extract is 2%～4%) its parts by weight are: 1～40 part of Radix Salviae Miltiorrhizae extract, 15～400 parts of Pollen Tyjphae extracts; Be preferably: 5～30 parts of Radix Salviae Miltiorrhizae extracts, 30～250 parts of Pollen Tyjphae extracts; More preferably: 15～20 parts of Radix Salviae Miltiorrhizae extracts, 60～120 parts of Pollen Tyjphae extracts.
The main effective ingredient of the Radix Salviae Miltiorrhizae extract in the aforementioned pharmaceutical compositions is a Radix Salviae Miltiorrhizae total phenolic acids, and content is not less than 70%, and wherein salvianolic acid B is not less than 30%; The main effective ingredient of Pollen Tyjphae extract is a flavone compound, and content is not less than 30%, preferably is not less than 50%.
Each drug component gets consumption and gropes in a large number to sum up to draw through the inventor in the pharmaceutical composition of the present invention, and the consumption of each component all has better curative effect in above-mentioned weight range.Above-mentioned composition as if being unit with the gram, can be made the preparation of 100～10000 consumptions.As tablet, can make 100～10000,1～10 of each consumption, every day 1～5 time.As injection, can make 100～10000,1～10 of each consumption, every day 1～3 time.More than form when producing and according to the corresponding proportion increase or to reduce, as large-scale production can be raw material with the kilogram, or is unit with the ton, and 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.Above ratio obtains through science screening, and for especial patient, the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.
Pharmaceutical composition of the present invention can be used for preparing the medicine for the treatment of cardiovascular and cerebrovascular disease.Has microcirculation improvement; reduce serum cholesterol, atherosclerosis increases coronary flow; reduce myocardial excitability and conductivity; the formation of antiplatelet gathering and thrombosis makes blood viscosity descend antioxidation; increase oxygen-resistant ability; anti-inflammation improves renal function, to the effects such as protection of cerebral tissue ischemia and reperfusion injury.
Pharmaceutical composition of the present invention can be mixed and made into clinically any or pharmaceutically acceptable dosage form with one or more pharmaceutically acceptable carriers, preferred oral preparation or injection are applied to the patient who needs this treatment in the mode of oral or parenteral.
When being used for oral administration, can be made into conventional solid preparation, as tablet, capsule, pill, granule etc.; Also can be made into oral liquid, as oral solution, oral suspensions, syrup etc.Tablet means disk shape or the special-shaped flaky solid preparation that medicine and the auxiliary materials and mixing compacting that suits form, based on oral ordinary tablet, other has buccal tablet, Sublingual tablet, mouth paster, chewable tablet, dispersible tablet, fuse, effervescent tablet, slow releasing tablet, controlled release tablet and enteric coatel tablets etc.Capsule means medicine or is added with the adjuvant filling in Capsules or be sealed in solid preparation in the soft capsule material, according to its dissolving and release characteristics, can be divided into hard capsule (being commonly referred to as capsule), soft capsule (soft gelatin capsule), slow releasing capsule, controlled release capsule and enteric coated capsule etc.Pill means medicine and suitable adjuvant uniform mixing, and the spherical or near-spherical solid preparation so that proper method is made comprises drop pill, sugar pill, piller etc.Granule means that medicine and suitable adjuvant make the dried particles shape preparation with certain particle size, can be divided into soluble particles (being commonly referred to as granule), mix suspension grain, effervescent granule, enteric coated particles, slow-releasing granules and controlled release granule etc.Oral solution means that medicine dissolution makes for oral supernatant liquid preparation in suitable solvent.Oral suspensions means the slightly solubility solid drugs, is dispersed in the liquid medium, makes for oral suspension body preparation, also comprises dry suspension or dense suspension.Syrup means the dense aqueous sucrose solution that contains medicine.
When being used for parenteral, can be made into injection.Injection means the intravital solution of confession injection, emulsion or the suspension that medicine is made and supplies to face with preceding preparation or be diluted to solution or the sterile preparation of the powder of suspension or concentrated solution that injection can be divided into injection, injectable sterile powder and concentrated solution for injection.Injection means that the confession that medicine is made is injected into sterile solution type injection, emulsion-type injection or the suspension type injection of using in the body, can be used for intramuscular injection, intravenous injection, intravenous drip etc.; Its specification has 1ml, 2ml, 5ml, 10ml, 20ml, 50ml, 100ml, 200ml, 250ml, 500ml etc., and wherein large volume (generally the being not less than 100ml) injection of using for intravenous drip also claims venous transfusion.Injectable sterile powder means that confession that medicine is made is faced with the suitable sterile solution of preceding usefulness and is mixed with settled solution or the evenly sterilized powder or the aseptic block of suspension, available suitable solvent for injection preparation back injection, also available venous transfusion preparation posterior vein instils; Sterilized powder makes with solvent crystallization, spray drying method or freeze-drying etc.Concentrated solution for injection means that confession that medicine is made faces the aseptic concentrated solution of using for intravenous drip with preceding dilution.
When pharmaceutical composition of the present invention is made oral formulations, can add suitable filler, binding agent, disintegrating agent, lubricant etc.Filler commonly used comprises starch, Icing Sugar, calcium phosphate, calcium sulfate two water things, dextrin, microcrystalline Cellulose, lactose, pregelatinized Starch, mannitol etc.; Typical binders comprises sodium carboxymethyl cellulose, PVP-K30, hydroxypropyl cellulose, starch slurry, methylcellulose, ethyl cellulose, hypromellose, gelling starch etc.; Disintegrating agent commonly used comprises dried starch, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose etc.; Conventional lubricants comprises magnesium stearate, Pulvis Talci, sodium lauryl sulphate, micropowder silica gel etc.
When making injection, optional use solvent or non-aqueous solvent can add suitable additives according to the character of medicine.The most frequently used aqueous solvent is a water for injection, also available 0.9% sodium chloride solution or other suitable aqueous solutions; Non-aqueous solvent commonly used is a vegetable oil, is mainly the injection soybean oil, and other also have the aqueous solution of ethanol, propylene glycol, Polyethylene Glycol etc.Additives commonly used comprise osmotic pressure regulator, pH value regulator, solubilizing agent, filler, antioxidant, antibacterial, emulsifying agent, suspending agent etc.Osmotic pressure regulator commonly used comprises sodium chloride, glucose, potassium chloride, magnesium chloride, calcium chloride, sorbitol etc., preferred sodium chloride or glucose; PH value regulator commonly used comprises acetic acid-sodium acetate, lactic acid, citric acid-sodium citrate, sodium bicarbonate-sodium carbonate etc.; Solubilizing agent commonly used comprises polyoxyethylene sorbitan monoleate, propylene glycol, lecithin, polyoxyethylene castor oil etc.; Filler commonly used comprises lactose, mannitol, sorbitol, dextran etc.; Antioxidant commonly used has sodium sulfite, sodium sulfite, sodium pyrosulfite etc.; Antibacterial commonly used is phenol, cresol, chlorobutanol etc.Injection container commonly used has glass ampule, vial, plastic ampoule, plastic bottle etc.
In sum, pharmaceutical composition of the present invention has the following advantages:
(1) adopts Radix Salviae Miltiorrhizae or its extract and Pollen Typhae or its extract reasonable compatibility first, be used to prepare the medicine for the treatment of cardiovascular and cerebrovascular disease, and confirm that by experiment both have synergistic function, be better than both independent medications.
(2) each proportioning of pharmaceutical composition of the present invention is carried out pharmacodynamic study, drawn the optimal proportion of pharmaceutical composition of the present invention.
(3) the pharmacological effect experimental studies results shows, pharmaceutical composition of the present invention can make in the ischemical reperfusion injury rat cerebral tissue NO content reduce, and ChAT content raises, and ET content reduces, and has and treats the cerebral ischemia ability preferably, can Synergistic; Significantly reduce myocardial infarction area; Improve the myocardial ischemia symptom, obviously suppress the phenomenon of arrhythmia; Reduce myocardial oxygen consumption, improve the ischemic myocardium contractile function, improve the active utmost point of SOD in the cardiac muscular tissue, reduction MDA content ,-OH content; Anticoagulant, blood viscosity lowering improves hemorheology and microcirculation; Increase mouse ear arteriole, venule caliber, accelerate blood flow rate, microcirculation improvement.Aspect resisting cardiovascular disease, has beyond thought effect.
(4) pharmacological effect experiment showed, that the drug effect of pharmaceutical composition of the present invention is better than using separately the drug effect of Radix Salviae Miltiorrhizae or its extract and Pollen Typhae or its extract, has synergistic function, and dosage reduces relatively, is with a wide range of applications.
(5) pharmaceutical composition effective ingredient of the present invention is clear and definite, the content height, and better stability of preparation, preparation technology is simple and easy to do, is convenient to control of quality, can guarantee clinical drug safety.
Below routine by experiment beneficial effect of further setting forth pharmaceutical composition of the present invention, these experimental examples comprise the pharmacodynamic experiment of pharmaceutical composition of the present invention, the compositions of Radix Salviae Miltiorrhizae or its extract and Pollen Typhae or its extract is hereinafter to be referred as red Pu compositions.Radix Salviae Miltiorrhizae extract in the experimental example comes from embodiment 1, and Pollen Tyjphae extract comes from embodiment 2.
Experimental example 1: red Pu compositions is to the influence of cerebral ischemia-reperfusion injury in rats
Laboratory animal: 210 of Wistar rats, male, body weight 250g ± 10g.
Test sample:
Radix Salviae Miltiorrhizae group: capsule of red sage root agent, self-control;
Pollen Typhae group: Pollen Typhae capsule, self-control;
Red Pu compositions group: red Pu composition capsule (various dose proportioning), self-control, 17 different proportioning groups, Radix Salviae Miltiorrhizae+Pollen Typhae: 200g+3000g, 200g+5000g, 200g+10000g, 500g+2000g, 500g+3000g, 500g+5000g, 500g+10000g, 1000g+2000g, 1000g+3000g, 1000g+5000g, 2000g+1000g, 2000g+2000g, 2000g+3000g, 2000g+5000g, 4000g+1000g, 4000g+3000g, 4000g+5000g.
Experimental technique:
Animal grouping: be divided into 21 groups at random, 10 every group.1. sham-operation (SAM) group: 5d puts to death after the sham-operation.2. ischemia-reperfusion (IR) is organized: pour into 5d behind the ischemia 30min again and put to death.3. Radix Salviae Miltiorrhizae group: the continuous irrigation stomach gave Radix Salviae Miltiorrhizae 5d (dosage is 45mg/kg) after ischemia 30min poured into 30min again, put to death behind the last administration 1h.4. Pollen Typhae is organized: the continuous irrigation stomach gave Pollen Typhae 5d (dosage is 45mg/kg) after ischemia 30min poured into 30min again, put to death behind the last administration 1h.5. red Pu compositions (Different Weight proportioning) group, 25 groups, the continuous irrigation stomach gave red Pu compositions 5d (dosage is 45mg/kg) after ischemia 30min poured into 30min again, put to death behind the last administration 1h.Get brain on ice rapidly, put in the liquid nitrogen frozen to be measured.
Animal model: the Wistar rat anesthesia, the 4VO legal system is equipped with the global brain ischemia animal model of reperfusion injury, by close the infusion time again of bilateral carotid control rat cerebral ischemia with the bulldog clamp folder.
Index detects:
Acetylcholine (Ach) is measured: Ach changes with choline acetylase (ChAT) in the cerebral tissue) activity represents that the active radiochemical method that adopts of ChAT carries out, and protein content is undertaken by the Lowry method in the tissue, and unit is μ mol/ (h.mg Pr).
Nitric oxide (NO) is measured: big rat brain tissue homogenate, the centrifugal 5min of 4000 * g gets supernatant 2ml and adds 1ml sodium acetate and 1ml P-aminobenzene-sulfonamide.Detect the pH scope 6.25～6.35, add zinc powder 10～15mg, the whirlpool 15min that shakes filters, get supernatant 4ml, add the 2.0ml developer, transfer pH to 1.75～1.85, add NaCl2.0g, n-butyl alcohol 3.0ml, the whirlpool shakes, and 3000 rev/mins of centrifugal 5min get supernatant, 540nm place test sample product absorbance.Biuret method test sample product protein content, NO content in the calculation sample, unit are nmol/mg Pr.
The mensuration of Endothelin (ET): press ET content in ET medicine box (PLA General Hospital) the description ria-determination brain tissue homogenate, unit is pg/mg Pr.
Statistical analysis technique: experimental data represents that with x ± s the t that more all adopts between two sample means checks.
Experimental result and conclusion: cerebral tissue NO, Ach, ET changes of contents after the Ischemia and Reperfusion in vivo in Rats see Table 1.
Ischemia-reperfusion group is compared with sham operated rats, and NO content raises in the rat cerebral tissue, and ChAT content reduces, and ET content raises, and difference extremely significantly (p＜0.01), illustrate that modeling is successful.Radix Salviae Miltiorrhizae group and sham operated rats compare, and NO content raises in the rat cerebral tissue, and ChAT content reduces, and ET content raises, significant difference (p＜0.05), the Pollen Typhae group compares with sham operated rats, and NO content raises in the rat cerebral tissue, ChAT content reduces, and ET content raises, significant difference (p＜0.05).Red Pu each dosage ratio group of compositions and ischemia-reperfusion group compare NO content reduction in the rat cerebral tissue, and ChAT content raises, and ET content reduces, difference is (p＜0.01) extremely significantly, and the Radix Salviae Miltiorrhizae group is compared with ischemia-reperfusion group, and NO content reduces in the rat cerebral tissue, ChAT content raises, ET content reduces, significant difference (p＜0.05), and Pollen Typhae and ischemia-reperfusion group are relatively, NO content slightly reduces in the rat cerebral tissue, ChAT content slightly raises, and ET content slightly reduces, and difference is not remarkable.The result shows that each dosage ratio group of red Pu compositions can both make NO content reduction in the ischemical reperfusion injury rat cerebral tissue, and ChAT content raises, and ET content reduces, and shows that Radix Salviae Miltiorrhizae and Pollen Typhae compatibility have the effect of collaborative anti-cerebral ischemia.The better effects if of each proportioning in 500～2000 parts of the Radix Salviae Miltiorrhizaes, 2000～4000 parts of scopes of Pollen Typhae; When 3000 parts of 1000 parts of Radix Salviae Miltiorrhizaes, Pollen Typhae, effect is best, points out it may be best proportioning.
The red Pu compositions of table 1 is to NO in the ischemical reperfusion injury rat cerebral tissue, and the influence of ChAT and ET content (x ± s, n=10)
Annotate:
*P＜0.05,
*P＜0.01 is compared with sham operated rats;
#P＜0.05,
##P＜0.01 is compared with ischemia-reperfusion group;
﹠amp;P＜0.05 is compared with the Radix Salviae Miltiorrhizae group;
$P＜0.05 is compared with the Pollen Typhae group.
Experimental example 2 red Pu compositionss are to the influence of rat experiment myocardial inyaretion scope
Animal subject: the Wistar rat, male, body weight 200～220g, 70.
Test sample:
Normal saline: commercial;
Radix Salviae Miltiorrhizae group: DANSHEN KELI agent, self-control;
Pollen Typhae group: Pollen Typhae granule, self-control;
Red Pu compositions group: (Radix Salviae Miltiorrhizae+Pollen Typhae=1000g+3000g), self-control is divided into high, medium and low three dosage groups to red Pu composition granule.
Experimental technique: rat is divided into 7 groups at random, 10 every group: blank group, model group, Radix Salviae Miltiorrhizae group, Pollen Typhae group, red Pu compositions group: high, medium and low three dosage groups.Each administration group is with normal saline and is mixed with gastric infusion behind the suspension.
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, gastric infusion.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 infarction plug district area accounts for the percentage ratio of ventricle and heart area, and carries out statistical procedures (t check).
The red Pu compositions of table 2 to the influence of rat experiment myocardial inyaretion scope (x ± s, n=10)
Annotate:
#P＜0.05 is compared with the blank group;
*P＜0.05,
*P＜0.01 is compared with model group;
﹠amp;P＜0.05 is compared with the Radix Salviae Miltiorrhizae group;
$P＜0.05 is compared with the Pollen Typhae group.
Experimental result and conclusion: experimental result sees Table 2.
(1) compare with the blank group, the myocardial infarction area of model group significantly increases (p＜0.05), and the modeling success is described.
(2) compare with model group, Radix Salviae Miltiorrhizae group myocardial infarction area significantly reduces (p＜0.05), and Pollen Typhae group myocardial infarction area significantly reduces (p＜0.05), and the high, medium and low dosage group of red Pu compositions myocardial infarction area all extremely significantly reduces (p＜0.01).
(3) compare with Radix Salviae Miltiorrhizae group, Pollen Typhae group, the anti-myocardial infarction effect of the high, medium and low dosage of red Pu compositions all is better than single effect with Radix Salviae Miltiorrhizae (p＜0.05) and Pollen Typhae (p＜0.05).
High, medium and low three the dosage groups of red Pu compositions all can significantly reduce myocardial infarction area, and are better than single effect with Radix Salviae Miltiorrhizae and Pollen Typhae, point out two medicine compatibilities that synergistic function is arranged, and action effect are relevant with dosage, and effect is best during high dose.
Experimental example 3 red Pu compositionss are to the research of experimental rat acute myocardial ischemia protective effect
Laboratory animal: the Wistar rat, 170, body weight is at 200 ± 30g, male and female half and half.
Test sample:
The blank group: normal saline, commercial;
Nitroglycerin group: nitroglycerine tablets, specification: 0.5mg, Beijing Yimin Pharmaceutical Co., Ltd.;
Radix Salviae Miltiorrhizae extract group: Radix Salviae Miltiorrhizae extract capsule, self-control;
That extract group of Pollen Typhae: Pollen Tyjphae extract capsule, self-control;
Red Pu compositions group: red Pu composition capsule (Radix Salviae Miltiorrhizae extract+Pollen Tyjphae extract), self-control.
Instrument: six road physiology monitors, Shanghai medical apparatus factory.
Experimental technique: get 170 of Wistar rats, be divided into 17 groups at random, every group 10, be respectively the blank group, the nitroglycerin group, the Radix Salviae Miltiorrhizae extract group, the Pollen Tyjphae extract group, red Pu compositions group: 13 groups (preparation method is referring to embodiment 4), Radix Salviae Miltiorrhizae extract+Pollen Tyjphae extract (5mg+60mg, 5mg+120mg, 5mg+250mg, 15mg+60mg, 15mg+120mg, 15mg+250mg, 20mg+30mg, 20mg+60mg, 20mg+120mg, 20mg+250mg, 30mg+30mg, 30mg+60mg, 30mg+250mg).Each administration group is with normal saline and is mixed with gastric infusion behind the suspension, and each treated animal is irritated stomach and give 1 time every day, continuous 7 days (nitroglycerin group before giving pituitrin sublingual vein injection 1 time).60min after the last administration in six road physiology monitors (Shanghai medical apparatus factory), connects limb lead and precordial leads with urethanes (1g/kg) intraperitoneal injection of anesthesia, in oscillograph observation and recording ecg.Behind the sublingual vein injection of pituitrin 5 μ l/kg, immediate record V3 electrocardiogram, and respectively trace 1 time in 15s, 30s, 1min, 2min, 5min, respectively organize vein and inject and move on the ECG ST section behind the pituitrin and amplitude that the T ripple raises, and observe each group and ARR number of animals occurs.
Acute Myocardial Ischemia in Rats electrocardiogram variation due to the red Pu compositions antagonism of table 3 pituitrin (x ± s, n=10)
Annotate:
*P＜0.05,
*P＜0.01, the blank group is compared;
﹠amp;P＜0.05 is compared with the Radix Salviae Miltiorrhizae extract group;
$P＜0.05 is compared with the Pollen Tyjphae extract group;
*P＜0.05 is compared with the Radix Salviae Miltiorrhizae extract group;
#P＜0.05 is compared with the Pollen Tyjphae extract group.
Experimental result and conclusion: give respectively to organize behind the pituitrin and move on the ECG ST section and amplitude that the T ripple raises and number of animals that arrhythmia occurs see Table 3, behind the injection of pituitrin, moving on the ST section appears in blank group most animals at once, reaches summit in the 2min, and 5min recovers substantially.Raising appears in T ripple 2min at once, recover gradually, but 5min does not return to normally thereupon.Move on nitroglycerin group and the red Pu compositions group ST section and raise time of occurring of T ripple consistent with matched group, but amplitude is significantly less than matched group, and recovers comparatively fast.Compare with Radix Salviae Miltiorrhizae extract group, Pollen Tyjphae extract group, the effect that the anti-electrocardiogram of each compositions proportioning group changes all is better than single effect with Radix Salviae Miltiorrhizae extract and Pollen Tyjphae extract, and significant difference (p＜0.05) is arranged.The effect of each proportioning is better in 15～20 parts of Radix Salviae Miltiorrhizae extracts, 60～120 parts of scopes of Pollen Typhae leaf extract, utmost point significant difference (p＜0.01) is arranged, and the arrhythmia number is few.
Experimental example 4 red Pu compositionss are to the influence of myocardial oxygen consumption and antioxidase
Laboratory animal: 42 of hybrid dogs, body weight 12.68kg ± 1.87kg, male and female half and half.
Test sample:
Radix Salviae Miltiorrhizae extract group: Radix Salviae Miltiorrhizae extract tablet, self-control;
Pollen Tyjphae extract group: Pollen Tyjphae extract tablet, self-control;
Red Pu compositions group: red Pu composition tablet (Radix Salviae Miltiorrhizae extract+Pollen Tyjphae extract=20mg+120mg), high, medium and low three various dose groups, self-control (preparation method is referring to embodiment 3).
Experimental technique: 42 dogs are divided into 7 groups, 6 every group at random: false ligation group, model control group, Radix Salviae Miltiorrhizae extract group, Pollen Tyjphae extract group, red Pu compositions group.Each administration group is with normal saline and is mixed with gastric infusion behind the suspension.
Dog myocardial infarction and ischemia model preparation: the administration expiration respectively organize dog intravenous injection pentobarbital sodium (30mgkg
-1) anaesthetize and fix, monitoring limbs II lead electrocardiogram; Set up the femoral vein passage, anticoagulant in the 0.5% heparin sodium body; Separate femoral artery, femoral arteriography continuous monitoring BP after the heparinization; Separate trachea and intubate, pedestrian worker's respirator positive pressure respiration (16～18 min of frequency
-1, air-breathing expiration is than 1: 1.5, tidal volume 350～550ml); Open breast and expose heart, separate the left coronary artery LC, connect blood flowmeter, measure coronary flow; Separate the below 2mm of left coronary artery anterior descending branch first branch, except that the not ligation of threading of false ligation group, all the other each groups all penetrate two No. 1 silk threads, 5min before the first phase ligation, and by per kilogram of body weight 2mg, vein splashes into lignocaine.Article one, handling diameter with one during the silk thread ligation is that No. 9 syringe needles of 1mm place between ligature and the blood vessel, after the ligation syringe needle is extracted out, carry out the first phase ligation of angiostenosis, behind the 30min, again with the ligation of second silk thread, carry out the second stage of ligation of bloodstream blocking, finish the preparation of myocardial infarction and ischemia model.
Detect index: blood oxygen saturation is measured: before ligation, first phase ligation 10mm, the second stage of ligation at once, 15min, 30min, 60min, 120min measure and the record coronary flow, and respectively get blood 1ml respectively at coronary sinus (venous blood), neck aorta before ligation and during the second stage of ligation 120min, measure blood oxygen saturation, by formula:
Myocardial oxygen consumption (MVO
2) ml/ (min100g)=coronary artery blood flow (CBF) ml/ (min100g) * (arterial blood oxygen ml%-coronary sinus blood oxygen ml%) calculate and respectively to organize myocardial oxygen consumption.
The SOD of cardiac muscular tissue, MDA ,-OH mensuration: each group of the second stage of ligation 120min is taken out heart immediately, get the left ventricle myocardium of apex of heart with the ice normal saline solution after washing, blotting, weigh and organize 1g, with the normal saline solution is medium, make the homogenate of 10% cardiac muscular tissue with homogenizer, measure SOD activity, MDA and-OH content.
Experimental result and conclusion: experimental result sees Table 4.
(1) to the influence of myocardial oxygen consumption: model group is compared myocardial oxygen consumption and is extremely significantly raise (p＜0.01) with false ligation group, and the modeling success is described.
(2) Radix Salviae Miltiorrhizae extract group, Pollen Tyjphae extract group, high, medium and low each the dosage group myocardial oxygen consumption of red Pu compositions all extremely significantly are lower than model group, and utmost point significant difference (p＜0.01) is arranged.
(3) compare with Radix Salviae Miltiorrhizae extract group, Pollen Tyjphae extract group with single, red Pu compositions group is better than single with Radix Salviae Miltiorrhizae extract group (p＜0.05) and Pollen Tyjphae extract group (p＜0.05).
(4) to SOD, MDA in the cardiac muscular tissue and-influence of OH: model group compares with false ligation group that the SOD activity extremely significantly raises (p＜0.01) in the cardiac muscular tissue, and MDA reaches-OH content extremely significantly reduces (p＜0.01); Radix Salviae Miltiorrhizae extract group, Pollen Tyjphae extract group, high, medium and low each the dosage group of red Pu compositions, the active utmost point of SOD is significantly higher than model group (p＜0.01) in the cardiac muscular tissue; MDA content ,-OH content significantly reduces and all extremely significantly is lower than model group (p＜0.01).
Red each dosage group of Pu compositions can significantly reduce the ischemic myocardium oxygen consumption behind the coronary ligation blocking blood flow; Improve free radical resisting enzymatic activity in the ischemic myocardial tissue, strengthen the ability that cardiac muscular tissue removes free radical, reduce the generation of myocardium peroxide and hydroxy radical, and be better than but with the effect of Radix Salviae Miltiorrhizae extract and Pollen Tyjphae extract, point out two medicine compatibilities to have synergistic function, and action effect is relevant with dosage, and effect is best during high dose.
Table 4PS to dog ischemic myocardium oxygen consumption and SOD, MDA ,-influence of OH (x ± s, n=6)
Annotate:
#P＜0.01 is with false ligation group ratio;
*P＜0.05,
*P＜0.01 is with the model group ratio;
﹠amp;P＜0.05 is compared with the Radix Salviae Miltiorrhizae extract group;
$P＜0.05 is compared with the Pollen Tyjphae extract group.
The antiplatelet aggregative activity of experimental example 5 red Pu compositionss
Animal subject: the Wistar rat, male, body weight 200～220g, 60.
Test sample:
The blank group: normal saline, commercial;
Radix Salviae Miltiorrhizae extract group: Radix Salviae Miltiorrhizae extract tablet, self-control;
Pollen Tyjphae extract group: Pollen Tyjphae extract tablet, self-control;
Red Pu compositions group: red Pu composition tablet (Radix Salviae Miltiorrhizae extract+Pollen Tyjphae extract), be equivalent to crude drug Radix Salviae Miltiorrhizae+Pollen Typhae=1000mg+3000mg, self-control (preparation method is referring to embodiment 3) is divided into high, medium and low three dosage groups.
Experimental technique: rat is divided into 6 groups at random, 10 every group, is respectively the blank group, Radix Salviae Miltiorrhizae extract group, Pollen Tyjphae extract group, the high, medium and low dosage group of red Pu compositions.Each administration group is with normal saline and is mixed with gastric infusion behind the suspension, 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.The centrifugal 5min of anticoagulated whole blood 1500r/min under 20 ℃ of conditions is obtained platelet rich plasma (PPR).After leaving and taking quantitative PPR, will remain PPR, obtain own control platelet poor plasma (PPP) once more with the centrifugal 10min of 3000r/min.Regulate PPR concentration with PPP, make each PPR concentration identical.PPR after the preheating, is added ADP (final concentration is 3 μ mol/L) and causes platelet aggregation in 37 ℃ constant temperature hole, the record maximum agglutination rate.
Experimental result and conclusion: experimental result sees Table 5.
(1) compare with the blank group, Radix Salviae Miltiorrhizae extract group and Pollen Tyjphae extract group platelet maximum agglutination rate all significantly reduce (p＜0.05), and each dosage group platelet maximum agglutination rate of compositions extremely significantly reduces (p＜0.01).
(2) compare with Radix Salviae Miltiorrhizae extract group, Pollen Tyjphae extract group, the platelet maximum agglutination rate of red each dosage group of Pu compositions significantly reduces (p＜0.05, p＜0.05).
Red each dosage of Pu compositions is remarkable anticoagulant all, and all be better than single effect with Radix Salviae Miltiorrhizae extract and Pollen Tyjphae extract, show that Radix Salviae Miltiorrhizae extract and Pollen Tyjphae extract compatibility have good synergism, and action effect is relevant with dosage, effect is best during high dose.
The antiplatelet aggregative activity of the red Pu compositions of table 5 (x ± s, n=10)
Annotate:
*P＜0.05,
*P＜0.01 is compared with the blank group;
﹠amp;P＜0.05 is compared with the Radix Salviae Miltiorrhizae extract group;
$P＜0.05 is compared with the Pollen Tyjphae extract group.
Experimental example 6: red Pu compositions influences microcirculation of mouse auricle
Animal subject: male mice, 60, body weight 20～25g is divided into 6 groups at random, 10 every group.
Test sample:
Matched group: normal saline, commercial.
Radix Salviae Miltiorrhizae extract group: Radix Salviae Miltiorrhizae extract tablet, self-control;
Pollen Tyjphae extract group: Pollen Tyjphae extract tablet, self-control;
Red Pu compositions group: red Pu composition tablet (Radix Salviae Miltiorrhizae extract+Pollen Tyjphae extract=20mg+120mg), high, medium and low three various dose groups, self-control (preparation method is referring to embodiment 3).
Experimental technique: mice is pressed the dosage gastric infusion of table 6, and matched group filling stomach gives the normal saline with volume, uses urethane 1g/kg intraperitoneal injection of anesthesia then.Postanesthetic mice places on the supporting plate that is covered with Cotton Gossypii, keeps 20 ± 2 ℃ of room temperatures.Mouse right ear is placed on the ear carriage, on auris dextra, drips a little liquid paraffin, supporting plate is put on the microscope carrier, regulate cold light source, make illuminating ray and auricle plane at 45～60 ° of angles, and parallel with the direction of growth of hair.Under low power lens, observe the auricle overall picture earlier, select suitable position, use high power lens instead and fix a point to observe continuously.The microcirculating state of 20min after the observation administration, the diameter and the blood flow rate of measurement arteriole, venule.
Experimental result and conclusion: experimental result sees Table 6.Compare with matched group, Radix Salviae Miltiorrhizae extract group and Pollen Tyjphae extract group all can make mouse ear arteriole, venule caliber obviously increase (p＜0.05), and blood flow rate is obviously accelerated (p＜0.05); Red each dosage group of Pu compositions all can make mouse ear arteriole, the venule caliber utmost point enlarge markedly (p＜0.01), and blood flow rate is extremely significantly accelerated (p＜0.01).Compare with the Pollen Tyjphae extract group with the Radix Salviae Miltiorrhizae extract group, each dosage group of red Pu compositions can make mouse ear arteriole, venule caliber obviously increase, and blood flow rate is obviously accelerated, and has significant difference (p＜0.05, p＜0.05).By The above results as can be seen, the effect of red Pu compositions all is better than Radix Salviae Miltiorrhizae extract and the individually dosed effect of Pollen Tyjphae extract, prompting Radix Salviae Miltiorrhizae extract and Pollen Tyjphae extract drug combination have synergistic function, and action effect is relevant with dosage, and effect is best during high dose.
The red Pu compositions of table 6 to microcirculation of mouse auricle influence (x ± s, n=10)
Annotate:
*P＜0.05,
*P＜0.01 is compared with matched group;
﹠amp;P＜0.05 is compared with the Radix Salviae Miltiorrhizae extract group;
$P＜0.05 is compared with the Pollen Tyjphae extract group.
Experimental example 7 red Pu compositionss are to the influence of myocardial ischemia due to the ligation rat coronary artery
Animal subject: rat, 60, body weight 200～220g, the male and female dual-purpose is divided into 6 groups at random, 10 every group.
Test sample:
The myocardial ischemia matched group: normal saline, commercial;
Radix Salviae Miltiorrhizae extract group: Radix Salviae Miltiorrhizae extract injection, self-control;
Pollen Tyjphae extract group: Pollen Tyjphae extract injection, self-control;
Red Pu compositions group: red Pu composite injection (Radix Salviae Miltiorrhizae extract+Pollen Tyjphae extract=20mg+120mg), high, medium and low three various dose groups, self-control (preparation method is referring to embodiment 8).
Experimental technique: rat is used urethane 1g/kg intraperitoneal injection of anesthesia, back of the body position is fixing, the record electrocardio connects artificial respirator and practices artificial respiration, and opens the thoracic cavity, cut off pericardium, each treated animal is pressed medicine intravenous administration (dosage unit: mg/kg), fall branch before the coronary artery of ligation left side behind the 3min, omnidistance record electrocardio 30min separately, 1h gets blood after the ligation, detects creatine phosphokinase (CK) and lactic acid dehydrogenase (LDH).Take out rat heart, with 4 of the even crosscuts of ventricular muscles, 0.5% chlorination nitro tetrazole is blue to dye along ligature, and with the ischemic areas on every myocardium two sides of planimeter survey, the calculating myocardium ischemic areas accounts for the percentage ratio of ventricle area.
The red Pu compositions of table 7 to the influence of myocardial ischemia due to the ligation rat coronary artery (X ± S, n=10)
Annotate:
*P＜0.05,
*Compare with the myocardial ischemia matched group in p＜0.01;
﹠amp;Compare with the Radix Salviae Miltiorrhizae extract group in p＜0.05;
$Compare with the Pollen Tyjphae extract group in p＜0.05.
Experimental result and conclusion: experimental result sees Table 7.After the ligation, the cardiac electrical QRS ripple of myocardial ischemia control rats all increases unusually suddenly, widens, and cardiac muscle is ischemia on a large scale, and biochemistry detection shows as CK and LDH all increases unusually.Compare with the myocardial ischemia matched group, each dosage group of red Pu composite injection all can extremely significantly reduce extremely significantly to reduce myocardial ischemia scope (p＜0.01) because of the electrocardio due to the ligation coronary artery and the abnormal change (p＜0.01) of biochemical indicator; Radix Salviae Miltiorrhizae extract group and Pollen Tyjphae extract group all can significantly reduce significantly to reduce myocardial ischemia scope (p＜0.05) because of the electrocardio due to the ligation coronary artery and the abnormal change (p＜0.05) of biochemical indicator.Compare with Radix Salviae Miltiorrhizae extract group or Pollen Tyjphae extract group with single, red Pu compositions group significantly reduces because of the electrocardio due to the ligation coronary artery and the abnormal change (p＜0.05) of biochemical indicator, significantly reduce myocardial ischemia scope (p＜0.05), prompting Radix Salviae Miltiorrhizae extract and Pollen Tyjphae extract have synergistic function, aspect the treatment ischemic cardiovascular significant curative effect will arranged.
[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 comes from embodiment 1, and Pollen Tyjphae extract comes from embodiment 2.
Embodiment 1 Radix Salviae Miltiorrhizae extract extraction process and preparation
The preparation of Radix Salviae Miltiorrhizae extract
Get red rooted salvia, be ground into coarse powder, decoct with water twice, 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 1.10～1.15 (60 ℃), 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.
Prepare three batches of Radix Salviae Miltiorrhizae extracts respectively, yield sees Table 8.
The assay of Radix Salviae Miltiorrhizae extract
Total phenolic content is measured
The preparation of reference substance solution: precision 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 of need testing solution: precision 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-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 of salvianolic acid B: high performance liquid chromatography
Chromatographic condition and system suitability experiment: with the octadecylsilane chemically bonded silica is filler; 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.
The preparation of reference substance solution: it is an amount of that precision takes by weighing the salvianolic acid B reference substance, adds 75% methanol and make the solution that every 1ml contains 0.14mg, promptly.
The preparation of need testing solution: get the about 0.2g of this product, the accurate title, decide, 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.
Algoscopy: accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly.
Three batches of Radix Salviae Miltiorrhizae extracts to above-mentioned preparation carry out assay respectively, and measurement result sees Table 8.
The assay result and the yield of table 8 Radix Salviae Miltiorrhizae extract
Embodiment 2 Pollen Tyjphae extract extraction process and preparations
The preparation of Pollen Tyjphae extract
Get cattail pollen, add 70% ethanol extraction three times, extracted 3 hours at every turn.First and second time adds 14 times of amounts of alcohol, adds 10 times of amounts of alcohol for the third time.Merge extractive liquid,, filter, filtrate recycling ethanol to relative density is the concentrated solution of 1.04～1.06 (50 ℃), adds to wait water gaging to dilute, mixing, 4 ℃ of cold preservation 24 hours, centrifugal, get supernatant, extract 2 times with the jolting of equivalent petroleum ether, discard petroleum ether liquid, water liquid extracts 3 times with the jolting of equivalent water-saturated n-butanol, merges n-butanol extracting liquid, be concentrated into dried, residue adds low amounts of water makes dissolving, last AB-8 macroporous resin column, water, 35% ethanol, 70% ethanol elution respectively, collect 70% ethanol elution, reclaim ethanol, drying under reduced pressure promptly gets Pollen Tyjphae extract.
Prepare three batches of Pollen Tyjphae extracts respectively, yield sees Table 9.
The assay of Pollen Tyjphae extract
Flavonoid content is measured
Chromatographic condition and system suitability: with the octadecylsilane chemically bonded silica is filler; With methanol-0.4% phosphoric acid liquid (50: 50) is mobile phase; The detection wavelength is 360nm; Calculate post with isorhamnetin, kaempferol, Quercetin and imitate, theoretical cam curve is 3000～4000.
The preparation of reference substance solution: accurate respectively Quercetin, nimbecetin, the isorhamnetin reference substance that takes by weighing through the phosphorus pentoxide dried overnight is an amount of, respectively adds methanol and makes the solution that every 1ml contains 0.04mg, 0.02mg, 0.1mg, in contrast product solution.Stepwise dilution is made into a series of reference substance solution respectively again, promptly.
The preparation of need testing solution: get Cattail Pollen 1.0g, the accurate title, decide, and puts in the 250ml conical flask, add methanol 100ml supersound extraction 40min, put cold filtration, get filtrate, extracting solution evaporate to dryness, residue add methanol 225% hydrochloric acid (4: 1) mixed liquor 25ml, backflow 45min, put cold, be transferred in the 50ml measuring bottle, add methanol, shake up to scale, get centrifugal in right amount, promptly.
Algoscopy: accurate respectively above-mentioned reference substance solution of absorption and need testing solution be 20 μ l respectively, inject the chromatograph of liquid injector of 5 μ l quantity tubes, measure, promptly.
Three batches of Pollen Tyjphae extracts to above-mentioned preparation carry out assay respectively, and measurement result sees Table 9.
The assay result and the yield of table 9 Pollen Tyjphae extract
The preparation of embodiment 3 red Pu composition tablets
Prescription one:
Radix Salviae Miltiorrhizae extract 17g is equivalent to crude drug 1kg
Pollen Tyjphae extract 32g is equivalent to crude drug 1kg
Pregelatinized Starch 100g
Microcrystalline Cellulose 30g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4g
Carboxymethylstach sodium 8g
Prepare 1000 altogether
Prescription two:
Radix Salviae Miltiorrhizae extract 17g is equivalent to crude drug 1kg
Pollen Tyjphae extract 63g is equivalent to crude drug 2kg
Pregelatinized Starch 110g
Microcrystalline Cellulose 35g
Low-substituted hydroxypropyl cellulose 35g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 5g
Carboxymethylstach sodium 10g
Prepare 1000 altogether
Prescription three:
Radix Salviae Miltiorrhizae extract 20g
Pollen Tyjphae extract 120g
Pregelatinized Starch 120g
Microcrystalline Cellulose 40g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 12g
Prepare 1000 altogether
Prescription four:
Radix Salviae Miltiorrhizae extract 17g is equivalent to crude drug 1kg
Pollen Tyjphae extract 158g is equivalent to crude drug 5kg
Pregelatinized Starch 130g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 50g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 9g
Carboxymethylstach sodium 15g
Prepare 1000 altogether
Prescription five:
Radix Salviae Miltiorrhizae extract 17g is equivalent to crude drug 1kg
Pollen Tyjphae extract 315g is equivalent to crude drug 10kg
Pregelatinized Starch 150g
Microcrystalline Cellulose 60g
Low-substituted hydroxypropyl cellulose 60g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 12g
Carboxymethylstach sodium 18g
Prepare 1000 altogether
Preparation technology:
Radix Salviae Miltiorrhizae in the raw material and Pollen Typhae are made extract with reference to the preparation method among the embodiment 1,2.
(1) it is standby Radix Salviae Miltiorrhizae extract and Pollen Tyjphae extract to be pulverized 100 mesh sieves.
(2) take by weighing raw material and adjuvant according to recipe quantity.
(3) hypromellose 2% the aqueous solution made soluble in water is standby.
(4) with Radix Salviae Miltiorrhizae extract, Pollen Tyjphae extract, pregelatinized Starch, microcrystalline Cellulose, low-substituted hydroxypropyl 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.
The preparation of embodiment 4 red Pu composition capsules
Prescription one:
Radix Salviae Miltiorrhizae extract 9g is equivalent to crude drug 0.5kg
Pollen Tyjphae extract 63g is equivalent to crude drug 2kg
Pregelatinized Starch 115g
Microcrystalline Cellulose 45g
Low-substituted hydroxypropyl cellulose 25g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 5g
Prepare 1000 altogether
Prescription two:
Radix Salviae Miltiorrhizae extract 9g is equivalent to crude drug 0.5kg
Pollen Tyjphae extract 95g is equivalent to crude drug 3kg
Pregelatinized Starch 120g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Prepare 1000 altogether
Prescription three:
Radix Salviae Miltiorrhizae extract 9g is equivalent to crude drug 0.5kg
Pollen Tyjphae extract 158g is equivalent to crude drug 5kg
Pregelatinized Starch 130g
Microcrystalline Cellulose 60g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 8g
Prepare 1000 altogether
Prescription four:
Radix Salviae Miltiorrhizae extract 35g is equivalent to crude drug 2kg
Pollen Tyjphae extract 63g is equivalent to crude drug 2kg
Pregelatinized Starch 120g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Prepare 1000 altogether
Prescription five:
Radix Salviae Miltiorrhizae extract 20g
Pollen Tyjphae extract 120g
Pregelatinized Starch 130g
Microcrystalline Cellulose 60g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 8g
Prepare 1000 altogether
Prescription six:
Radix Salviae Miltiorrhizae extract 35g is equivalent to crude drug 2kg
Pollen Tyjphae extract 158g is equivalent to crude drug 5kg
Pregelatinized Starch 140g
Microcrystalline Cellulose 70g
Low-substituted hydroxypropyl cellulose 50g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 10g
Prepare 1000 altogether
Preparation technology:
Radix Salviae Miltiorrhizae in the raw material and Pollen Typhae are made extract with reference to the preparation method among the embodiment 1,2.
(1) with Radix Salviae Miltiorrhizae extract and and Pollen Tyjphae extract to pulverize 100 mesh sieves standby.
(2) take by weighing raw material and adjuvant according to recipe quantity.
(3) hypromellose 2% the aqueous solution made soluble in water is standby.
(4) with Radix Salviae Miltiorrhizae extract, Pollen Tyjphae extract, pregelatinized Starch, microcrystalline Cellulose, low-substituted hydroxypropyl 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.
The preparation of embodiment 5 medicinal composition soft capsules of the present invention
Prescription one:
Radix Salviae Miltiorrhizae extract 17g is equivalent to crude drug 1kg
Pollen Tyjphae extract 95g is equivalent to crude drug 3kg
Soybean oil 500g
Soybean phospholipid 30g
Cera Flava 15g
Prepare 1000 altogether
Prescription two:
Radix Salviae Miltiorrhizae extract 20g
Pollen Tyjphae extract 95g
Soybean oil 500g
Soybean phospholipid 30g
Cera Flava 15g
Prepare 1000 altogether
Preparation technology:
Radix Salviae Miltiorrhizae in the raw material and Pollen Typhae are made extract with reference to the preparation method among the embodiment 1,2.
(1) soybean oil of recipe quantity and soybean phospholipid, Cera Flava heating and melting, mixing is put cold;
(2) add Radix Salviae Miltiorrhizae extract and Pollen Tyjphae extract, mixing is crossed colloid mill;
(3) sampling, the semi-finished product chemical examination;
(4) be pressed into soft capsule;
(5) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 6 red Pu composition granules
Prescription one:
Radix Salviae Miltiorrhizae extract 9g is equivalent to crude drug 0.5kg
Pollen Tyjphae extract 32g is equivalent to crude drug 1kg
Icing Sugar 1000g
Steviosin 10g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription two:
Radix Salviae Miltiorrhizae extract 9g is equivalent to crude drug 0.5kg
Pollen Tyjphae extract 315g is equivalent to crude drug 10kg
Icing Sugar 3000g
Steviosin 30g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription three:
Radix Salviae Miltiorrhizae extract 35g is equivalent to crude drug 2kg
Pollen Tyjphae extract 32g is equivalent to crude drug 1kg
Icing Sugar 1900g
Steviosin 14g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription four:
Radix Salviae Miltiorrhizae extract 35g is equivalent to crude drug 2kg
Pollen Tyjphae extract 315g is equivalent to crude drug 10kg
Icing Sugar 3500g
Steviosin 35g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription five:
Radix Salviae Miltiorrhizae extract 6g is equivalent to crude drug 0.2kg
Pollen Tyjphae extract 63g is equivalent to crude drug 2kg
Icing Sugar 1600g
Steviosin 12g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription six:
Radix Salviae Miltiorrhizae extract 6g is equivalent to crude drug 0.2kg
Pollen Tyjphae extract 95g is equivalent to crude drug 3kg
Icing Sugar 2000g
Steviosin 15g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription seven:
Radix Salviae Miltiorrhizae extract 20g
Pollen Tyjphae extract 120g
Icing Sugar 2500g
Steviosin 20g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription eight:
Radix Salviae Miltiorrhizae extract 70g is equivalent to crude drug 4kg
Pollen Tyjphae extract 95g is equivalent to crude drug 3kg
Icing Sugar 2800g
Steviosin 25g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Preparation technology:
Radix Salviae Miltiorrhizae in the raw material and Pollen Typhae are made extract with reference to the preparation method among the embodiment 1,2.
(1) it is standby sucrose to be pulverized 80 mesh sieves; It is standby that Radix Salviae Miltiorrhizae extract and Pollen Tyjphae extract were pulverized 100 mesh sieves.
(2) take by weighing raw material and adjuvant according to recipe quantity.
(3) the method mix homogeneously that Radix Salviae Miltiorrhizae extract, Pollen Tyjphae extract and Icing Sugar, steviosin 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, sprays into an amount of Fructus Citri Limoniae essence.
(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.
The preparation of embodiment 7 red Pu composition oral liquid
Prescription one:
Radix Salviae Miltiorrhizae extract 15g
Pollen Tyjphae extract 60g
Propylene glycol 1000ml
Sodium benzoate 15g
Stevioside 10g
Purified water adds to 10000ml
Prepare 1000 altogether
Prescription two:
Radix Salviae Miltiorrhizae extract 15g
Pollen Tyjphae extract 120g
Propylene glycol 1000ml
Sodium benzoate 20g
Stevioside 15g
Purified water adds to 10000ml
Prepare 1000 altogether
Prescription three:
Radix Salviae Miltiorrhizae extract 20g
Pollen Tyjphae extract 60g
Propylene glycol 1000ml
Sodium benzoate 15g
Stevioside 10g
Purified water adds to 10000ml
Prepare 1000 altogether
Prescription four:
Radix Salviae Miltiorrhizae extract 20g
Pollen Tyjphae extract 120g
Propylene glycol 1000ml
Sodium benzoate 25g
Stevioside 20g
Purified water adds to 10000ml
Prepare 1000 altogether
Preparation technology:
(1) fully with heated and stirred dissolving in the purified water of Radix Salviae Miltiorrhizae extract and Pollen Tyjphae extract adding dosing amount 50%; It is complete to add the propylene glycol stirring and dissolving again.
(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 0.8 μ m.
(5) semi-finished product chemical examination.
(6) fill.Finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 8 red Pu composite injections
Prescription one:
Radix Salviae Miltiorrhizae extract 15g
Pollen Tyjphae extract 60g
Polysorbate 10g
Water for injection 2000ml
Prepare 1000 altogether
Prescription two
Radix Salviae Miltiorrhizae extract 15g
Pollen Tyjphae extract 120g
Polysorbate 20 g
Water for injection 2000ml
Prepare 1000 altogether
Prescription three:
Radix Salviae Miltiorrhizae extract 20g
Pollen Tyjphae extract 60g
Polysorbate 10g
Water for injection 2000ml
Prepare 1000 altogether
Prescription four:
Radix Salviae Miltiorrhizae extract 20g
Pollen Tyjphae extract 120g
Polysorbate 20 g
Water for injection 2000ml
Prepare 1000 altogether
Preparation technology:
(1) will produce with the ampoule dosing with vessel, instrument and equipment etc. clear up, degerming, depyrogenation;
(2) take by weighing raw material and adjuvant by prescription;
(3) get the water for injection that Polysorbate adds dosing amount 80%, stirring and dissolving; The needle-use activated carbon that adds dosing amount 0.05% stirs 15min, filters, and takes off charcoal;
(4) in solution, add Radix Salviae Miltiorrhizae extract and Pollen Tyjphae extract, stirring and dissolving;
(5) pH value of survey solution, adjust pH in case of necessity;
(6) benefit adds to the full amount of water for injection standardize solution;
(7) medicinal liquid is checked clarity through the microporous filter membrane fine straining of 0.22 μ m;
(8) inspection of semifinished product;
(9) medicinal liquid is loaded in the ampoule;
(10) 100 ℃ of flowing steam sterilization 30min;
(11) leak detection, lamp inspection;
(12) finished product is examined entirely, the packing warehouse-in.
Claims (10)
1. a pharmaceutical composition that is used for cardiovascular and cerebrovascular disease is characterized in that, make its contained composition and effectiveness crude drug consist of Radix Salviae Miltiorrhizae and Pollen Typhae, its parts by weight are: 200～4000 parts of Radix Salviae Miltiorrhizaes, 1000～10000 parts of Pollen Typhaes.
2. pharmaceutical composition according to claim 1 is characterized in that, the parts by weight of Radix Salviae Miltiorrhizae and Pollen Typhae are: 500～2000 parts of Radix Salviae Miltiorrhizaes, 2000～5000 parts of Pollen Typhaes.
3. pharmaceutical composition according to claim 2 is characterized in that, the parts by weight of Radix Salviae Miltiorrhizae and Pollen Typhae are: 1000 parts of Radix Salviae Miltiorrhizaes, 3000 parts of Pollen Typhaes.
4. according to the described arbitrary preparation of drug combination method of claim 1～3, it is characterized in that, described Radix Salviae Miltiorrhizae and Pollen Typhae can be with The suitable solvent respectively or mix through extracting processing and obtain its extract, total extract is made preparation with the pharmaceutic adjuvant hybrid process again, and the main effective ingredient of gained total extract is phenolic acids and flavone compound.
5. pharmaceutical composition according to claim 1 is characterized in that, this pharmaceutical composition can also be made by Radix Salviae Miltiorrhizae extract and Pollen Tyjphae extract, and its parts by weight are: 1～40 part of Radix Salviae Miltiorrhizae extract, 15～400 parts of Pollen Tyjphae extracts.
6. pharmaceutical composition according to claim 5 is characterized in that, its parts by weight are: 5～30 parts of Radix Salviae Miltiorrhizae extracts, 30～250 parts of Pollen Tyjphae extracts.
7. pharmaceutical composition according to claim 6 is characterized in that, its parts by weight are: 15～20 parts of Radix Salviae Miltiorrhizae extracts, 60～120 parts of Pollen Tyjphae extracts.
8. according to the described arbitrary pharmaceutical composition of claim 5～7, it is characterized in that the main component of described Radix Salviae Miltiorrhizae extract is a Radix Salviae Miltiorrhizae total phenolic acids, content is not less than 70%, and wherein the content of salvianolic acid B is not less than 30%; The main component of Pollen Tyjphae extract is a flavone compound, and content is not less than 30%.
9. according to claim 1～3,5～7 described arbitrary pharmaceutical compositions, it is characterized in that this pharmaceutical composition can combine with arbitrary acceptable accessories and make clinically any or pharmaceutically acceptable dosage form.
10. pharmaceutical composition according to claim 9 is characterized in that, clinically described or pharmaceutically acceptable dosage form is oral formulations or injection.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2006100692775A CN101161268B (en) | 2006-10-12 | 2006-10-12 | Pharmaceutical composition of red sage root and cattail pollen |
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Non-Patent Citations (4)
| Title |
|---|
| 张武.药对心析.江西中医药24 1.1993,24(1),50-51. |
| 张武.药对心析.江西中医药24 1.1993,24(1),50-51. * |
| 黄桂秋.蒲黄、丹参对纤维蛋白损伤内皮细胞的保护作用.上海第二医科大学学报7 2.1987,7(2),128-131. |
| 黄桂秋.蒲黄、丹参对纤维蛋白损伤内皮细胞的保护作用.上海第二医科大学学报7 2.1987,7(2),128-131. * |
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