CN101084998B

CN101084998B - Compound red sage root freezing-dried powder injection

Info

Publication number: CN101084998B
Application number: CN 200610014223
Authority: CN
Inventors: 叶正良; 李永强; 郑永锋; 周桂荣
Original assignee: Tianjin Tasly Zhijiao Pharmaceutical Co Ltd
Current assignee: Tianjin Tasly Zhijiao Pharmaceutical Co Ltd
Priority date: 2006-06-08
Filing date: 2006-06-08
Publication date: 2011-10-26
Anticipated expiration: 2026-06-08
Also published as: CN101084998A

Abstract

The present invention provides a compound red sage root freeze dried powder injection which comprises root of red rooted saliva, notoginseng, baras camphor through extracting root of red rooted saliva, notoginseng to obtain red sage root extract, pseudo-ginseng extract, finally dissolving baras camphor with right amount of ethanol. Calculated by the total amount of ginseng saponin Rg1 (C27H32O16), ginseng saponin Rb1, the content of notoginseng saponin R1 is 12.5-50.0mg/g of freeze-dried powder solid. Calculated by Danshensu (C9H10O5), the content of notoginseng is 2.5-15.5mg/g freeze-dried powder solid. Calculated by salvianolic acid B (C36H30O16), the content of salvia miltiorrhizae is 12.5-75.0mg/g of freeze-dried powder solid. Calculated by D-borneol (C10H180), the content of baras camphor is12.5-62.5mg/g of freeze-dried powder solid.

Description

A kind of compound red sage root freezing-dried powder injection

Technical field

The invention belongs to field of medicaments, more particularly, relating to Chinese medicine is that raw material is made a kind of compound red sage root freezing-dried powder injection.

Background technology

In most of western countries, cardiovascular diseases's death accounts for half of total death toll, and wherein coronary heart disease accounts for the first place, accounts for more than 50% of cardiovascular death number.As Asian countries, coronary heart disease is seen not as American-European countries in China more, but in recent years the trend of increasing is arranged.According to the vital statistics data that Ministry of Public Health is announced, the death of nineteen fifty-seven urbanite cardiovascular and cerebrovascular disease accounts for and rose to 16.6% in total 12.0%, 1989 year, and cause of the death cis-position rises to 2,3 by the 5th, 7.This shows that evidence of coronary heart diseases increases year by year, most of people's cardiovascular risk factors also is ascendant trend continuously and healthily.Patients with coronary heart disease is except causing that myocardial infarction causes the death because of arteria coronaria blocks, and anginal frequent outbreak also will make its study, ability to work limited greatly, and personal lifestyle can not be taken care of oneself when serious, and family and society have all been brought white elephant.Therefore, since the seventies, one of state key problem has been classified in the preventing and controlling of coronary heart disease as, along with the increase of Incidence of CHD, developing and effectively preventing, to treat coronary heart disease, anginal medicine is a very significant job to reduce cardiovascular disease to the threat of human health.

Modern medicine study is thought, heart is given mechanical irritation do not cause pain, but myocardial ischemia-anoxemia then causes pain.Conflict between the needs of blood supply coronarius and cardiac muscle, coronary artery blood flow can not satisfy the needs of myocardial metabolism, when causing rapid, temporary transient ischemia of cardiac muscle and anoxia, promptly produces angina pectoris.Modern medicine is the oxygen consumption that improves blood supply coronarius and alleviate cardiac muscle to the Therapeutic Principle of primary disease, treats atherosclerosis simultaneously.Can the use effect during angina pectoris attacks nitric acid preparation faster.Commonly used have nitroglycerin 0.3～0.6mg, a sublingual administration; Isosorbide dinitrate 5～10mg, sublingual administration etc.Ill effect has giddy, distending pain in the head, head beat sense, flushing, cardiopalmus etc., and idol has blood pressure drops.Prolonged and repeated application can be renderd a service attenuating owing to producing drug resistance.Catabasis is avoided the various factors that are enough to lead to outbreak that know as far as possible.The persistent antianginal drug of use effect, in case angina pectoris attacks, commonly used having (1) nitrate preparations (isosorbide dinitrate, pentaerythritol tetranitrate preparation etc.); (2) adrenergic (propranolol, oxprenolol, pindolol, metoprolol etc.), but this class medicine might cause untoward reaction, the unexpected inactive possibilities that cause myocardial infarction that have such as postural hypotension; (3) calcium channel blocker (verapamil, nifedipine etc.), but the danger of excessive inhibition heart is arranged, the improper coronary vasospasm that might cause of this class medicine of stopping using; (4) coronary artery dilator (persantin, molsidomine, amiodarone etc.), this class medicine especially persantin can reduce side and props up the circulation blood flow, cause what is called " coronary artery is stolen blood " phenomenon, myocardial ischemia is increased the weight of, though in clinical a lot of arguement commonly used.In addition, the operation of execution ACBG and two kinds of therapeutic method of surgery of percutaneous transluminal coronary angioplasty have also been risen in recent years gradually.But can can operation improve ventricular function, after making severe arrhythmia, heart failure or myocardial infarction do not take place, prolong patient's life-span, still do not have final conclusion; In addition operation itself can concurrent myocardial infarction, but the blood vessel thromboembolism that postoperative is transplanted, so operative indication is strict, is not to be fit to most of patients with coronary heart disease.

Chinese medicine is the important means of preventing and treating coronary heart disease.At primary disease, adopt two methods of taking stopgap measures and effect a permanent cure according to motherland's medical science determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs.Take stopgap measures, mainly use, based on " leading to ", invigorate blood circulation, blood stasis dispelling, method of treatment such as regulate the flow of vital energy, activate yang, reduce phlegm in the pain phase; Effect a permanent cure, generally use, based on regulating YIN and YANG, internal organs, QI and blood, YANG invigorating, YIN nourishing arranged, fill blood, method such as conditioning viscera in the catabasis.Wherein commonly used with " activating blood and removing stasis Method " (compound recipe or Chinese patent medicine that contains Chinese medicines such as Radix Paeoniae Rubra, Radix Salviae Miltiorrhizae, Flos Carthami, Rhizoma Chuanxiong, Pollen Typhae, Radix Curcumae commonly used) and " aromatic herbs activating YANG method " (Styrax Pilulae commonly used, Subing drop pills, the chest stuffiness relieving ball, heart pill, Heart pill of Musk etc.).But existing Chinese medicine patent medicine is based on decoction and compound recipe pill, and dose is big, carries inconvenience, and onset waits shortcoming slowly.Freeze-dried powder preparation is the advanced dosage form of Chinese medicine, and it is slow to overcome the oral formulations onset, can overcome the problem of injection poor stability again, compare with other dosage form, the lyophilized powder good stability has effectively avoided prescription Chinese medicine generation compatibility to change, and has kept curative effect when prolonging preparation effect duration; Next technology advanced person, effective substance purity is higher; Also can keep the biologic activity of effective ingredient in the compound Salviae Miltiorrhizae lyophilized powder to greatest extent in addition, thereby meet clinical needs, have broad clinical application prospect.

Summary of the invention

The object of the present invention is to provide a kind of compound red sage root freezing-dried powder injection.

Compound red sage root freezing-dried powder injection of the present invention is to be made by following raw materials in part by weight: Radix Salviae Miltiorrhizae 1000～4000g, Radix Notoginseng 260～850g, Borneolum Syntheticum 5～50g.

Preferred compound red sage root freezing-dried powder injection of the present invention is to be made by following raw materials in part by weight: Radix Salviae Miltiorrhizae 2000～3000g, Radix Notoginseng 360～550g, Borneolum Syntheticum 15～35g.

Best compound red sage root freezing-dried powder injection of the present invention is to be made by following raw materials in part by weight: Radix Salviae Miltiorrhizae 2486.2g, Radix Notoginseng 486.2g, natural Broneolum Syntheticum 27.6g.

In the medicine of the present invention, Radix Salviae Miltiorrhizae is a monarch drug, promoting blood circulation to remove obstruction in the collateral, the silt pain relieving of dispelling; Being equipped with Radix Notoginseng is minister, blood circulation promoting and blood stasis dispelling, removing obstruction in the collateral to relieve pain; The Borneolum Syntheticum refreshment of having one's ideas straightened out, three medicines share, and can reach the effect of blood circulation promoting and blood stasis dispelling, regulating QI to relieve pain.

Effective ingredient of the present invention can adopt following method: water extraction, decoction and alcohol sedimentation technique, alcohol extracting-water precipitating, extraction, infusion process, percolation, reflux extraction, continuous backflow extraction method, macroreticular resin absorbing method preparation.

The preparation method of compound red sage root freezing-dried powder injection active component of the present invention comprises the steps:

A. it is standby to get above-mentioned recipe quantity Radix Salviae Miltiorrhizae, Radix Notoginseng, Borneolum Syntheticum;

B. above three flavors, Radix Salviae Miltiorrhizae decocts with water, collecting decoction, and concentrate, concentrated solution adds ethanol, leaves standstill, and filters, and filtrate concentrates, concentrated solution adds ethanol, leaves standstill, and filters, and filtrate concentrates, and adds water, and cold preservation filters, filtrate concentrates, and adds ethanol, leaves standstill, and filters, and filtrate concentrates, and drying gets Radix Salviae Miltiorrhizae extract;

Radix Notoginseng decocts with water, and collecting decoction concentrates, and adds ethanol, leaves standstill, filter, filtrate concentrates, and adds water, and cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, the reuse ethanol elution is collected ethanol elution, is concentrated into thick paste, and drying gets Radix Notoginseng extract;

Get HP-, add water, heating makes dissolving, adds active carbon and boils, and takes off charcoal, filtrate for later use; With an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution, enclose filters, and gets Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution, promptly.

In the compound lyophilized powder of the present invention, contain Radix Salviae Miltiorrhizae extract, Radix Notoginseng extract and Borneolum Syntheticum.

In the compound red sage root freezing-dried powder injection of the present invention, wherein Radix Notoginseng is with ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 three's total content is 6.25～56.25mg/g freeze-dried powder solid content.

Compound red sage root freezing-dried powder injection of the present invention, wherein Radix Salviae Miltiorrhizae is with danshensu (C ₉H ₁₀O ₅) meter, content is 1.25～18.75mg/g lyophilized powder solid content.

Compound red sage root freezing-dried powder injection of the present invention, wherein Radix Salviae Miltiorrhizae is with salvianolic acid B (C ₃₆H ₃₀O ₁₆) meter, content is 6.25～100.00mg/g lyophilized powder solid content.

Compound red sage root freezing-dried powder injection of the present invention, wherein Borneolum Syntheticum is with dextro Borneolum Syntheticum (C ₁₀H ₁₈O) meter, content is 6.25～75.0mg/g lyophilized powder solid content.

Compound red sage root freezing-dried powder injection of the present invention, wherein ginsenoside Rg ₁(C ₂₇H ₃₂O ₁₆) 2.5～25.5mg/ bottle freeze-dried powder solid content, ginsenoside Rb ₁3.2～24.5mg/ bottle freeze-dried powder solid content, Panax Notoginseng saponin R ₁0.55～6.25mg/g freeze-dried powder solid content.

Compound red sage root freezing-dried powder injection of the present invention, wherein Radix Notoginseng is with ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), the total amount meter of ginsenoside Rb1, arasaponin R1, content is 12.5～50.0mg/g lyophilized powder solid content; Radix Salviae Miltiorrhizae is with danshensu (C ₉H ₁₀O ₅) meter, content is 2.5～15.5mg/g lyophilized powder solid content; Radix Salviae Miltiorrhizae is with salvianolic acid B (C ₃₆H ₃₀O ₁₆) meter, content is 12.5～75.0mg/g lyophilized powder solid content; Borneolum Syntheticum is with dextro Borneolum Syntheticum (C ₁₀H ₁₈O) meter, content is 12.5～62.5mg/g lyophilized powder solid content.

Preferred compound red sage root freezing-dried powder injection, wherein Radix Notoginseng is with ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), the total amount meter of ginsenoside Rb1, arasaponin R1, content is 18.75～31.25mg/g lyophilized powder solid content; Radix Salviae Miltiorrhizae is with danshensu (C ₉H ₁₀O ₅) meter, content is 3.75～12.75mg/g lyophilized powder solid content; Radix Salviae Miltiorrhizae is with salvianolic acid B (C ₃₆H ₃₀O ₁₆) meter, content is 25.0～50.125mg/g lyophilized powder solid content; Borneolum Syntheticum is with dextro Borneolum Syntheticum (C ₁₀H ₁₈O) meter, content is 25.0～50.25mg/g lyophilized powder solid content.

Best compound red sage root freezing-dried powder injection, wherein Radix Notoginseng is with ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), the total amount meter of ginsenoside Rb1, arasaponin R1, content is 18.75～25.0mg/g lyophilized powder solid content; Radix Salviae Miltiorrhizae is with danshensu (C ₉H ₁₀O ₅) meter, content is 3.75～8.875mg/g lyophilized powder solid content; Radix Salviae Miltiorrhizae is with salvianolic acid B (C ₃₆H ₃₀O ₁₆) meter, content is 25.0～41.375mg/g lyophilized powder solid content; Borneolum Syntheticum is with dextro Borneolum Syntheticum (C ₁₀H ₁₈O) meter, content is 31.25～41.5mg/g lyophilized powder solid content.

In the above-mentioned compound lyophilized powder, Radix Notoginseng is with the ginsenoside Rg1, the ginsenoside Rb1, and arasaponin R1 total amount meter, content is measured according to high performance liquid chromatography (" an appendix VI of Chinese pharmacopoeia version in 2005 D).

Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica, are mobile phase with the acetonitrile-water gradient elution; The detection wavelength is 203nm.Number of theoretical plate calculates by the ginsenoside Rg1 peak should be not less than 2000.

The linear gradient elution proportion of mobile phase changes program

The preparation of reference substance solution respectively precision to take by weighing ginsenoside Rg1, ginsenoside Rb1, arasaponin R1 reference substance an amount of, add methanol respectively and make the solution that every 1ml contains 0.5mg, 0.5mg, 0.2mg, shake up, promptly.

This product content under the content uniformity item is got in the preparation of need testing solution, and mixing is got 0.5g, accurate claims surely, puts in the 10ml measuring bottle, is dissolved in water and is diluted to scale, shakes up, and microporous filter membrane (0.45um) filters, 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, and calculate, promptly.

This product contains Radix Notoginseng with ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), the total amount meter of ginsenoside Rb1, arasaponin R1, content is 6.25～56.25mg/g freeze-dried powder solid content.

In the above-mentioned compound lyophilized powder, Radix Salviae Miltiorrhizae is measured according to high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 D) in danshensu content.

Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Acetonitrile-0.1% phosphoric acid (8: 92) is mobile phase; The detection wavelength is 280nm.Number of theoretical plate calculates by the danshensu sodium peak should be not less than 3000.

It is an amount of that the preparation precision of reference substance solution takes by weighing the danshensu sodium reference substance, adds methanol and make the solution that every 1ml contains 0.1mg, shakes up, promptly.

This product content under the content uniformity item is got in the preparation of need testing solution, and mixing is got 0.4g, accurate claims surely, puts in the 25ml measuring bottle, is dissolved in water and is diluted to scale, shakes up, and microporous filter membrane (0.45um) filters, promptly.

Accurate reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, and promptly get (every 1mg danshensu sodium is equivalent to the 0.880mg danshensu).

This product contains Radix Salviae Miltiorrhizae with danshensu (C ₉H ₁₀O ₅) meter, content is 1.25～18.75mg/g lyophilized powder solid content.

In the above-mentioned compound lyophilized powder, Radix Salviae Miltiorrhizae is in salvianolic acid B, and content is measured according to high performance liquid chromatography (" an appendix VI of Chinese pharmacopoeia version in 2005 D).

Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica, are mobile phase with acetonitrile-0.1% phosphoric acid (24: 76); The detection wavelength is 288nm.Number of theoretical plate calculates by the salvianolic acid B peak should be not less than 3000.

It is an amount of that the preparation precision of reference substance solution takes by weighing the salvianolic acid B reference substance, adds methanol and make the solution that every 1ml contains 0.15mg, shakes up, promptly.

This product content under the content uniformity item is got in the preparation of need testing solution, and mixing is got 0.15g, accurate claims surely, puts in the 50ml measuring bottle, is dissolved in water and is diluted to scale, shakes up, and microporous filter membrane (0.45um) filters, promptly.

This product contains Radix Salviae Miltiorrhizae with salvianolic acid B (C ₃₆H ₃₀O ₁₆) meter, content is 6.25～100.00mg/g lyophilized powder solid content.

In the above-mentioned compound recipe freeze-dried powder, content of bornyl alcohol is in dextro Borneolum Syntheticum, and content is measured according to gas chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 E).

Chromatographic condition and system suitability test chromatographic column: INNOWAX (30m*0.32mm*0.5um), column temperature: temperature programming: 150 ℃ keep 7min, rise to 220 ℃ with 20 ℃/min, keep 5min.Vapourizing temperature: 250 ℃; Detector temperature: 250 ℃; Detector: FID flame ionization ditector, hydrogen flowing quantity: 40ml/min; Air mass flow: 350ml/min; Carrier gas: high-purity nitrogen; Carrier gas flux: 2ml/min, tail blows 30ml/min; Input mode: split ratio 5: 1.Number of theoretical plate calculates by the dextro Borneolum Syntheticum peak should be not less than 1900.

It is an amount of that the mensuration of correction factor is got methyl salicylate, and accurate the title decides, and adds the solution that dehydrated alcohol is mixed with 1mg/ml, as inner mark solution.It is an amount of to get the dextro Borneolum Syntheticum reference substance, and accurate the title decides, and adds the solution that dehydrated alcohol is made 1mg/ml, precision is measured 0.5ml in the 10ml measuring bottle again, is diluted to scale with dehydrated alcohol behind the accurate adding inner mark solution 1ml, shakes up, draw 1ul, inject gas chromatograph, the calculation correction factor.

Algoscopy is got 5 bottles of this product, and inclining content, mixing, precision takes by weighing in right amount (being equivalent to 1 bottle amount approximately), in the 25ml measuring bottle, after the water 5ml dissolving, be diluted to scale with dehydrated alcohol, shake up, precision is measured 0.5ml in the 10ml measuring bottle again, be diluted to scale with dehydrated alcohol behind the accurate adding inner mark solution 1ml, shake up, filter, draw subsequent filtrate 1ul, inject gas chromatograph is measured, promptly.

This product contains Borneolum Syntheticum with dextro Borneolum Syntheticum (C for every bottle ₁₀H ₁₈O) meter, content is 6.25～75.0mg/g lyophilized powder solid content.

Medicine of the present invention can adopt the preparation of Chinese medicine preparation conventional method.Also these crude drug can be ground into powder mixes evenly makes powder and takes after mixing it with water; Also can be with these medicines decocting together, the condensed water decocting liquid is made oral liquid then; Also can the raw materials used medicated powder of medicine of the present invention is broken, with crude drug ground ingredients and adjuvant mix homogeneously, direct compression.The medicine activity component that the present invention can adopt the said extracted method to obtain is made said dosage form on any pharmaceutics with present common medicament theory with adjuvant; As tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, suck dosage forms such as agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, solution, ointment, plaster, spray, drop pill, soft capsule, injection, lyophilized injectable powder, but preferably adopt following method to extract crude drug, and be prepared into lyophilized injectable powder, below just further specify, but this is not construed as limiting the invention of the present invention.

The preparation method of compound red sage root freezing-dried powder injection of the present invention comprises the steps:

A. it is standby to get recipe quantity Radix Salviae Miltiorrhizae, Radix Notoginseng, Borneolum Syntheticum;

B. above Radix Salviae Miltiorrhizae, Radix Notoginseng be through extracting or close extraction respectively, Radix Salviae Miltiorrhizae extract, Radix Notoginseng extract or Radix Salviae Miltiorrhizae, Radix Notoginseng are closed extract; An amount of dissolve with ethanol of Borneolum Syntheticum is used beta-cyclodextrin inclusion compound;

Radix Salviae Miltiorrhizae extract, Radix Notoginseng extract or Salvia miltiorrhiza and Panax notoginseng extract are added the injection water make dissolving in right amount, boil, put coldly, filter, filtrate is mixed with Borneolum Syntheticum β-CDBao He solution, and with mannitol, it is an amount of to add water for injection, accent pH, and lyophilizing, promptly.

The preparation method of preferred compound red sage root freezing-dried powder injection of the present invention comprises the steps:

B. above three flavors, Radix Salviae Miltiorrhizae decocts with water, collecting decoction, and concentrate, concentrated solution adds ethanol, leaves standstill, and filters, and filtrate concentrates, concentrated solution adds ethanol, leaves standstill, and filters, and filtrate concentrates, and adds water, and cold preservation filters, filtrate concentrates, and adds ethanol, leaves standstill, and filters, and filtrate concentrates, and drying gets Radix Salviae Miltiorrhizae extract; Radix Notoginseng decocts with water, and collecting decoction concentrates, and adds ethanol, leaves standstill, filter, filtrate concentrates, and adds water, and cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, the reuse ethanol elution is collected ethanol elution, is concentrated into thick paste, and drying gets Radix Notoginseng extract; Get HP-, add water, heating makes dissolving, adds active carbon and boils, and takes off charcoal, filtrate for later use; With an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution, enclose filters, and gets Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution;

Radix Salviae Miltiorrhizae extract and Radix Notoginseng extract are added the injection water respectively make dissolving in right amount, boil, put and be chilled to room temperature, cold preservation filters, and filtrate merges, add active carbon, charcoal is taken off in insulation, mix with Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution filtrate cooling back, with mannitol, it is an amount of to add water for injection, transfers pH, lyophilizing, promptly.

B. above three flavors, the Radix Salviae Miltiorrhizae section decocts with water each 0.5～3 hour 1～5 time, collecting decoction, and be concentrated into the extractum that relative density is 1.05～1.35 (50 ℃) adds ethanol and makes and contain the alcohol amount and reach 50～85%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adding ethanol makes and contains the alcohol amount and reach 85%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.15～1.45 (50 ℃), add 2～14 times of water gagings, cold preservation filters, and filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adding ethanol makes and contains the alcohol amount and reach 50～90%, leave standstill, filter, filtrate is concentrated into thick paste, drying gets Radix Salviae Miltiorrhizae extract; Get Radix Notoginseng, decoct with water 1～5 time, each 0.5～3 hour, collecting decoction, and be concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), and add ethanol and make and contain the alcohol amount and reach 50～90%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adds 1～10 times of water gaging, cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, reuse 50～85% ethanol elutions are collected ethanol elution, be concentrated into thick paste, drying gets Radix Notoginseng extract; Get HP-100～1500g, add water in right amount, heating makes dissolving, adds 0.2～1% active carbon and boils 5～60 minutes, takes off charcoal, filtrate for later use.With an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution, ultrasonic enclose 1～12 hour filters, and gets Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution;

Radix Salviae Miltiorrhizae extract and Radix Notoginseng extract are added the injection water respectively make dissolving in right amount, boiled 1～20 minute, put and be chilled to room temperature, cold preservation filters, and filtrate merges, add 50～90 ℃ of insulations of 0.05～0.2% active carbon 10～60 minutes, take off charcoal, filtrate is cooled to back below 70 ℃ mixes with Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution, with mannitol 20～300g, add water for injection to an amount of, transferring pH is 5～7, lyophilizing, promptly.

The preparation method of best compound red sage root freezing-dried powder injection of the present invention comprises the steps:

B. above three flavors, the Radix Salviae Miltiorrhizae section decocts with water each 1 hour three times, collecting decoction, and be concentrated into the extractum that relative density is about 1.15 (50 ℃) adds ethanol and makes and contain the alcohol amount and reach 75%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is about 1.15 (50 ℃), adding ethanol makes and contains the alcohol amount and reach 85%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is about 1.25 (50 ℃), add 8～10 times of water gagings, cold preservation filters, and filtrate is concentrated into the extractum that relative density is about 1.15 (50 ℃), adding ethanol makes and contains the alcohol amount and reach 80%, leave standstill, filter, filtrate is concentrated into thick paste, drying gets Radix Salviae Miltiorrhizae extract; Get Radix Notoginseng powder and be broken into granule, decoct with water three times, each 1 hour, collecting decoction, and be concentrated into the extractum that relative density is about 1.15 (50 ℃), and add ethanol and make and contain the alcohol amount and reach 80%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is about 1.15 (50 ℃), adds 3～5 times of water gagings, cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, reuse 70% ethanol elution is collected 70% ethanol elution, be concentrated into thick paste, drying gets Radix Notoginseng extract; Get HP-500g, add water to 1500ml, heating makes dissolving, adds 0.5% active carbon and boils 20 minutes, takes off charcoal, filtrate for later use.With an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution, ultrasonic enclose 6 hours filters, and gets Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution;

Radix Salviae Miltiorrhizae extract and Radix Notoginseng extract are added the injection water respectively make dissolving in right amount, boiled 10 minutes, put and be chilled to room temperature, cold preservation, filter, filtrate merges, and adds 80 ℃ of insulations of 0.1% active carbon 30 minutes, take off charcoal, filtrate is cooled to back below 50 ℃ mixes with Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution, with mannitol 100g, add water for injection to 4000ml, transferring pH is 6.5, and degerming filters, fill adds butyl rubber bung to cillin bottle, lyophilizing, gland, check, packing is promptly.

More than form when producing and to increase or to reduce according to corresponding ratio, as large-scale production can be unit with kilogram or with the ton, small-scale production can be unit with the gram also, and weight can increase or reduce, but the crude drug material weight proportion constant rate between each composition.

For a better understanding of the present invention, below learn the beneficial effect that the invention medicine is further set forth in test, test the effect that is intended to further specify medicine below by medicine effect of the present invention, but not limitation of the present invention.

Experimental example: the pharmacodynamics test of injection use compound Radix Salviae Miltiorrhizae lyophilized powder

1 experiment material

1.1 medicine

Be subjected to the reagent thing: compound Salviae Miltiorrhizae lyophilized powder (sample before the lyophilizing): provide specification by Tianjin and this Bioisystech Co., Ltd: 300g/100ml/ bottle, lot number: 030307; Positive control medicine: XIANGDAN ZHUSHEYE, Jiangsu Kang Yi pharmaceutical Co. Ltd product, product batch number: 030710-1.

1.2 reagent

Urethanes (urethane) is Shanghai San Pu chemical industry company limited product, lot number: 20030812; Pentobarbital sodium is Shanghai chemical reagents corporation product, lot number: F20020915; The pituitrin injection is by Shanghai first biochemical Pharma Inc. and biochemical-pharmaceutical factory, Shanghai Joint Production, lot number: 040301; Blue tetrazolium (UNI-CHEM Chemical Reogents), lot number: GD3010034; ADP and collagen, Sigma company product, final concentration are 3.5 μ mol/L.

1.3 instrument

BL-410 biological function experimental system is Sichuan Province Chengdu TME Technology Co., Ltd. product; The animal artificial respirator, DH-150 type, Medical Instrument Factory affiliated to Zhejiang Univ production; It is Japanese photoelectricity company product that RM-6000 type four road physiology are led instrument more, and used plug-in unit is respectively floating ground formula bioelectric amplifier (AT-601G), carrier amplifier (AP-621G), blood pressure recorder (AP-611G), Cardiotacs (AT-601G); MF-1200 type Electromagnetic Flow is counted Japanese photoelectricity company product; Constant Temp. Oven is a Changsha medical apparatus and instruments factory product; HH-W600 digital display three is used thermostatic water tank, is Jintan City, Jiangsu Province high honour instrument Manufacturing Co., Ltd product; Laser Doppler flowmetry (PeriFluxSystem5000, PERIMED, USA); The LDZ5-2 centrifuge is Beijing Medical Centrifugal Machine Factory's product; Blood gas analyzer (USA Insyrumentation Laboratory, Gem-3000 type) and biochemical automated analysis instrument (USAVIROS-950 type); TYXN-91 type intelligence platelet aggregation instrument (Shanghai uncle bio tech ltd difficult to understand); System CA-530 hemorheology instrument (U.S.).

1.4 dosage setting

With reference to clinical medicine dose, cause test such as rat heart muscle ischemia influence in conjunction with the chmice acute hypoxia endurance test, to clotting time of mice influence and to pituitrin and draw various animals administer dosage, as follows:

Rat low dosage: 0.30g/kg, middle dosage: 0.60g/kg, high dose: 1.20g/kg;

Dog low dosage: 0.09g/kg, middle dosage: 0.18g/kg, high dose: 0.36g/kg;

Mice low dosage: 0.44g/kg, middle dosage: 0.88g/kg, high dose: 1.76g/kg;

XIANGDAN ZHUSHEYE: dog: 0.53ml/Kg, rat: 1.8ml/Kg, mice: 2.6ml/kg.

Drug dilution method, route of administration and volume: that gets same lot number respectively tests used medicine, with the normal saline preparation, now prepares existing usefulness every day; Route of administration: intravenous injection or lumbar injection; Various units administration volume is respectively: mice is the 0.15ml/10g body weight; Rat is 0.3ml/100g; Dog is the 3.0ml/kg body weight.

1.5 laboratory animal

A cleaning level Kunming mouse, body weight 18～22g, male and female half and half, the quality certification number: 2002A055; A cleaning level SD rat, male and female half and half, body weight 180～230g, the quality certification number: 2003A070; New zealand white rabbit, body weight 2.0～2.5kg, male and female are not limit, the quality certification number: 2003A034; The hybrid dog, body weight 11.0～14.0kg provides by Zhongshan University's Experimental Animal Center.

The raising condition: after animal entered cleaning level Animal Lab., the every cage of mice was put 10 in a suitable place to breed, and the every cage of rat is put 5 in a suitable place to breed, by special messenger's feeding and management.Animal housing's lighting every day 12 hours, heating ventilation and air-conditioning equipment is good, and room temperature is controlled at 25 ± 1 ℃, and relative humidity is 40～50%.Laboratory is sterilization regularly routinely.

1.6 statistical method

All (x ± s) expression relatively uses Student ' s t check to experimental result between the group of measurement data, relatively adopt paired t-test before and after the test of measurement data with average ± standard deviation.

2 experiment and results

2.2 compound Salviae Miltiorrhizae is to the influence of acute myocardial ischemia dog cardiac muscle

2.2.1 experimental technique

30 of healthy hybrid dogs, body weight 11.0～14.0kg, male and female all have, be divided into dosage group (0.18g/kg), compound Salviae Miltiorrhizae lyophilized powder high dose group (0.36g/kg) and XIANGDAN ZHUSHEYE group (0.53ml/kg) in sham operated rats, model group (normal saline), compound Salviae Miltiorrhizae lyophilized powder low dose group (0.09g/kg), the compound Salviae Miltiorrhizae lyophilized powder at random, every group of 5 animals.3% pentobarbital sodium (30mg/kg) intravenous injection row general anesthesia, back of the body position is fixing.Standby from right jugular vein intubate as blood drawing.Tracheostomize inserts tracheal casing pipe, connect the capable malleation artificial respiration of animal respirator (16 times/min).Right arm reclining is fixed, and opens breast in left IV intercostal, cuts off pericardium, exposes left anterior descending coronary artery (LAD) threading standby (doing ligation), puts 9 electrodes and make thought-read adventitia electrograph and use on the pericardium of appropriate location down.Surgical injury finishes, treat that all observation indexs are stable after, record normal index and blood drawing.Ligation arteria coronaria left anterior descending branch (LAD) duplicates myocardial infarction and ischemia model, stablizes 30min record index, then respectively by each group dosage intravenous drip administration (dripping off in the control 15min).The epicardial electrogram of each some when 30min, 60min, 120min after 30min and the administration before drawing blood respectively and writing down the ligation arteria coronaria, behind the ligation arteria coronaria.In the experimentation, the variation that continuous monitoring electrocardiogram II leads.

Trace epicardial electrogram and electrocardiogram with collection of BL-410 bio signal and analytical equipment.

2.2.2 observation index

1. to the influence of myocardial ischemia scope: 1. trace epicardial electrogram at each time point with BL-410 bio signal system respectively, electrocardiogram ischemia scope (N-ST) is raised the summation of counting that exceeds 2mv with ST section in whenever leading and is represented.Degree of myocardial ischemia (∑-ST) represent with the summation of rising of ST section or fall in whenever leading.2. to the mensuration of myocardial infarct size: behind 180min, take off heart and carry out the NBT of cardiac muscular tissue dyeing, measure the scope (infarcted region/left chamber heavy * 100%) of infarction with weight method.

2. sero-enzyme is measured: respectively at getting blood during 180min before pricking and after the administration, separation of serum is used automatic biochemical analyzer and is measured serum lactate dehydrogenase (SLD) (LDH) and creatine phosphokinase (CPK).

2.2.3 experimental result

1. to the influence of myocardial ischemia dog myocardial ischemia scope

(1) to the influence of epicardial electrogram N-ST and ∑-ST

Following table 10 shows, after the model control group ligation after N-ST and ∑-ST ligation 30min 120min after the medication do not see significant change, injection gives the N-ST of compound Salviae Miltiorrhizae lyophilized powder and XIANGDAN ZHUSHEYE group and ∑-ST all less than the ischemia model group, middle and high dosage is obvious especially, prompting compound Salviae Miltiorrhizae lyophilized powder can effectively dwindle the myocardial ischemia scope, alleviates the degree of myocardial ischemia.

Table 10 compound Salviae Miltiorrhizae lyophilized powder is to myocardial ischemia dog epicardial electrogram influence (n=5, x ± s)

Compare with model group, ^*P＜0.05, ^*P＜0.01

(2) to the influence of myocardial infarct size

Table 11 shows: each dosage group of compound Salviae Miltiorrhizae lyophilized powder can obviously reduce the myocardial ischemia scope, and high dose group is the most obvious, and middle dosage group is suitable with the positive control drug effect.

The influence of table 11 pair myocardial ischemia dog myocardial infarction scope (x ± s)

Compare with model group, ^*P＜0.05, ^*P＜0.01

2. to sero-enzyme (LDH, CK) influence of level

Following table is 12 results show, obviously do not change before and after sham operated rats dog myocardium enzyme LDH and the CK medication, and coronary ligation dog myocardium enzyme LDH and CK all significantly raise than sham operated rats or before performing the operation.Compound Salviae Miltiorrhizae and XIANGDAN ZHUSHEYE more all have the effect that reduces myocardial ischemia dog serum LDH and CPK level with model group.

The influence of table 12 couple myocardial ischemia dog LDH and CK (x ± s)

Compare with model group, ^*P＜0.05, ^*P＜0.01

3. to the influence of myocardial ischemia due to the pituitrin

3.1 experimental technique

70 of SD rats, body weight 180～230g divides 7 groups at random, and 10 every group, male and female half and half.With urethane 1200mg/Kg intraperitoneal injection of anesthesia.Back of the body position is fixing, gathers the lead electrocardiogram with analytical equipment record II with the BL-410 bio signal.Each organizes rat respectively from lumbar injection or irritate stomach and give following medicine: 1. model group (lumbar injection, ip.): normal saline 3.0ml/kg; 2. compound Salviae Miltiorrhizae lyophilized powder low dosage (ip.) is organized: 0.30g/kg; 3. dosage (ip.) is organized in the compound Salviae Miltiorrhizae lyophilized powder: 0.60g/kg; 4. compound Salviae Miltiorrhizae lyophilized powder high dose (ip.) is organized: 1.20g/kg); 5. compound Salviae Miltiorrhizae lyophilized powder low dosage (is irritated stomach, po.) group: 0.60g/kg; 6. compound Salviae Miltiorrhizae lyophilized powder high dose (po.) is organized: 1.20g/kg; 7. XIANGDAN ZHUSHEYE (ip.) is organized: 1.80ml/kg.Successive administration 3 days, once a day, behind the last administration 30min (1h after the administration of filling stomach group), each is organized rat and causes myocardial ischemia by sublingual vein injection of pituitrin 1u/kg respectively, observe and write down the before and after II lead electrocardiogram of 5s, 10s, 15s, 30s, 1min, 3min, 10min of every rat injection of pituitrin, measure the variation of each time point electrocardiogram index, each group result is carried out relatively reaching between group of administration front and back compare.

3.2 observation index

(1) J point displacement (mv) J point is the end of a period point of QRS ripple, and displacement is exactly the change that the position has taken place, and raises or forces down;

(2) T wave amplitude (mv)

(3) heart rate (inferior/min) behind the intravenous injection pituitrin, animal occurs the electrocardiogram ischemia immediately and changes, show as that the J point is raised or forced down, the T wave height is alarmmed or low flat, arrhythmia such as ventricular premature contraction, bradycardia, chamber conduction group stagnate etc., the variation of above several indexs before and after the pituitrin given in record.

3.3 experimental result

By table 13, table 14 and table 15 as seen, give pituitrin after, rat takes place obviously to change because of myocardial ischemia causes electrocardiogram, as J point raise, phenomenons such as the T wave height is alarmmed, arrhythmia and decreased heart rate, change is the most remarkable during with 10s, 15s.Compare with model control group, the spoke degree of raising that basic, normal, high three the dosage groups of compound Salviae Miltiorrhizae lyophilized powder can obviously reduce the rat electrocardiogram J point due to the pituitrin (compares with model group, P＜0.05 or P＜0.01), the spoke degree of T ripple rising also obviously reduces (P＜0.05) than model group.Compound Salviae Miltiorrhizae lyophilized powder intravenously administrable effect is better than the effect of gastric infusion.

5. the compound Salviae Miltiorrhizae lyophilized powder is to the influence of platelet and thrombosis

5.1 influence to extracorporeal platelet aggregation

Get blood from the rabbit arteria auricularis, get blood with the silication test tube, with 3.8% sodium citrate (1/10 blood volume) anticoagulant, centrifugal 10 minutes of 800r/min, sucking-off upper strata platelet rich plasma (PRP), centrifugal with 3000r/min again, take out platelet poor plasma (PPP).With PPP transmittance is transferred to 100, then with PRP zeroing, adds stirring rod, add normal saline or compound Salviae Miltiorrhizae lyophilized powder (0.002,0.004,0.008g/ml) and XIANGDAN ZHUSHEYE (0.05ml/ml), 37 ℃ of incubations.PRP is moved to the mensuration hole, add ADP (final concentration is 3.5 μ mol/L) or collagen (final concentration is 30 μ g/ml), observe the maximum aggregation extent of 5min, instrument is TYXN-91 type intelligence platelet aggregation instrument (Shanghai primary bio tech ltd difficult to understand).Calculate the platelet aggregation percentage rate (Plateletaggregation, PAG) or suppress to assemble percentage rate.

By following table 16,17 results as seen, the compound Salviae Miltiorrhizae lyophilized powder has the obvious suppression effect to ADP or collagen-induced rabbit platelet aggregation, along with the increase inhibitory action of dosage strengthens gradually, promptly its inhibitory action to ADP or collagen-induced rabbit platelet aggregation has tangible dose dependent.

Table 16 compound Salviae Miltiorrhizae lyophilized powder is to the influence of the inductive external rabbit platelet aggregation of ADP (PAG) (x ± s)

Compare with the buffer matched group, ^*P＜0.05, ^*P＜0.01

Table 17 compound Salviae Miltiorrhizae lyophilized powder is to the influence of collagen-induced external rabbit platelet aggregation (PAG) (x ± s)

Compare with the buffer matched group, ^*P＜0.05, ^*P＜0.01

5.2 to the thrombotic influence of rat artery-vein bypass

50 of SD rats, be divided into 5 groups at random, every group 10, the anesthesia of 10% chloral hydrate 3.5ml/kg lumbar injection (ip) is fixing, respectively from sublingual vein give XIANGDAN ZHUSHEYE (1.8ml/kg), compound Salviae Miltiorrhizae lyophilized powder high dose group (1.2g/kg), dosage group (0.6g/kg), low dosage (0.3g/kg), model group gives isometric normal saline.30min after administration separates right carotid and left side external jugular vein.Put into No. 4 silk threads of a long 6cm in the polyethylene tube stage casing, (50 μ l/ml) is full of polyethylene tube with heparin-saline solution.After an end of polyethylene tube inserted left external jugular vein, other end plastic tube injected heparin (50 μ l/m) 0.2ml anticoagulant, and then this end is inserted right carotid.Open bulldog clamp, allow blood in the right carotid inflow pipe, return the left side external jugular vein, behind the open blood 15min, middle Herba Clinopodii, the thrombosis that takes out rapidly in the polyethylene tube is weighed on analytical balance, obtains thrombosis suppression ratio (%).

Thrombosis suppression ratio=[(matched group wet weight of thrombus-administration group wet weight of thrombus) * 100%]/matched group wet weight of thrombus

By following table 18 as seen, high, medium and low three dosage of compound Salviae Miltiorrhizae lyophilized powder all can obviously suppress the formation of rat arteriovenous shut thrombosis, and at designed 0.3g/kg to 1.2g/kg, the increase effect of random quantity strengthens.

Table 18 compound Salviae Miltiorrhizae lyophilized powder to the total artery-vein of rat neck form the thrombosis influence (x ± s, n=10)

Compare with model group ^*P＜0.05, ^*P＜0.01

6. the compound Salviae Miltiorrhizae lyophilized powder is to clotting time and hemorheological influence

6.1 the compound Salviae Miltiorrhizae lyophilized powder is to the influence of clotting time of mice

Method: 70 of mices, body weight 18～22g, the male and female dual-purpose is divided into 7 groups at random by body weight and sex, and the administration volume is the 0.15ml/10g body weight.Give the intravenous injection normal saline solution respectively, 0.22g/kg, 0.44g/kg, the compound Salviae Miltiorrhizae lyophilized powder of 0.88g/kg, 1.76g/kg, 3.52g/kg, and 2.6ml/kg XIANGDAN ZHUSHEYE.30min after the administration gets blood with glass capillary from eyeball, and slide method is measured clotting time.

By following table 19 as seen, five dosage of compound Salviae Miltiorrhizae lyophilized powder 0.22～3.52g/kg all have the effect that prolongs clotting time of mice, and 0.22～1.76g/kg strengthens with the increase effect of agent, no longer increases greater than the 1.76g/kg effect.

Table 19 compound Salviae Miltiorrhizae lyophilized powder to the influence of clotting time of mice (x ± s, n=10)

6.2 the compound Salviae Miltiorrhizae lyophilized powder is to the influence of hemorheology of rat

Method: 50 of SD rats, be divided into 5 groups at random, every group 10, respectively from lumbar injection give XIANGDAN ZHUSHEYE (1.8ml/kg), compound Salviae Miltiorrhizae lyophilized powder high dose group (1.2g/kg), dosage group (0.6g/kg), low dosage (0.3g/kg), matched group gives isometric normal saline.Every day 1 time, counted 7,30min after the last administration, use the etherization rat, get blood 1.8ml from rat coeliac artery, adding rapidly has in the mensuration pipe of 1:9 sodium citrate solution 0.2ml, adopts and measures each whole blood viscosity, plasma viscosity (η p), blood relative viscosity (η r), erythrocyte aggregation index (AI), yield stress (CVS), Kazon viscosity (CV) with hemorheology instrument (U.S.'s product).

The result: whole blood viscosity, plasma viscosity and the reduced viscosity of rat when following table 20 visible compound Salviae Miltiorrhizae lyophilized powder high dose group can obviously reduce different shear rate, reduce erythrocyte aggregation index, middle dosage group can obviously reduce height and cut whole blood viscosity.Prompting compound Salviae Miltiorrhizae lyophilized powder can improve the effect of hemorheology function.

Table 20-1 compound Salviae Miltiorrhizae lyophilized powder to the influence of hemorheology of rat index (x ± s, n=10)

Compare with model group ^*P＜0.05, ^*P＜0.01

Table 20-2 compound Salviae Miltiorrhizae lyophilized powder to the influence of hemorheology of rat index (x ± s, n=10)

Compare with model group ^*P＜0.05, ^*P＜0.01

7. the compound Salviae Miltiorrhizae lyophilized powder is to the influence of mice hypoxia-bearing capability

70 of mices, male and female half and half are divided into 7 groups at random, 10 every group.The following medicine of intravenous injection respectively: 1. normal saline 0.15ml/10g; 2. compound Salviae Miltiorrhizae lyophilized powder 0.22g/kg; 3. compound Salviae Miltiorrhizae lyophilized powder 0.44g/kg; 4. compound Salviae Miltiorrhizae lyophilized powder 0.88g/kg; 5. compound Salviae Miltiorrhizae lyophilized powder 1.76g/kg; 6. compound Salviae Miltiorrhizae lyophilized powder 3.52g/kg; 7. XIANGDAN ZHUSHEYE 2.6ml/kg.The per injection capacity is 0.15ml/10g.Injected and distinguished lumbar injection isoprenaline (15mg/kg) again in 30 minutes, one by one mice being put into capacity then is the anoxia bottle that 250ml, bottom are covered with the 5g sodica calx, covers the bottle stopper that scribbles vaseline, causes the seal anoxia.Write down the airtight bottleneck time, constantly observe white mice respiratory frequency, the degree of depth, skin and lip change in color, cease breathing up to animal, write down the death time, from the lid bottle stopper to the breathless persistent period of animal during as the survival of mice under the anoxia condition, time-to-live of medication group and matched group relatively.

By table 21 as seen, each dosage group mice time-to-live under the normobaric hypoxia condition of compound Salviae Miltiorrhizae lyophilized powder has prolonged 23.20% (P＞0.05), 35.57% (P＞0.05), 55.15% (P＜0.05), 76.29% (P＜0.01), 78.35% (P＜0.01) respectively than matched group, prompting compound Salviae Miltiorrhizae lyophilized powder can improve the hypoxia-bearing capability of mice, and is comparatively remarkable with 1.76g/kg.

Table 21 compound Salviae Miltiorrhizae lyophilized powder to the influence of hypoxia endurance time (x ± s, n=10)

Compare with model group ^*P＜0.05, ^*P＜0.01

Experiment showed, to dog intravenous injection compound Salviae Miltiorrhizae lyophilized powder 0.18g/kg and 0.36g/kg can increase the heart acting, obviously increase cardiac output and coronary artery blood flow; Dwindle electrocardiogram ischemia scope and the degree of myocardial ischemia of coronary ligation dog, the infringement that myocardial ischemia is caused has the protective effect of dose dependent.Compound Salviae Miltiorrhizae lyophilized powder energy anticoagulant suppresses thrombus in vivo and forms in addition, prolongs clotting time, improves hemorheology index and improves the mice hypoxia-bearing capability.Showing that this medical instrument has tangible activating blood circulation to dissipate blood stasis and function of resisting myocardial ischemia, is the active drug of control myocardial ischemia disease, has important exploitation to be worth.This research prompting: the compound Salviae Miltiorrhizae lyophilized powder has the function that strengthens heart pump, increase coronary blood flow, resist myocardial ischemia-anoxemia, dwindle the functions such as cardiac damage due to the severe cardiac myocardial ischemia.

The specific embodiment

The present invention will be further described below in conjunction with embodiment, and following each embodiment only is used to the present invention is described and is not limitation of the present invention.

Embodiment 1:

A. get recipe quantity Radix Salviae Miltiorrhizae 1000g, Radix Notoginseng 850g, Borneolum Syntheticum 5g is standby;

B. above Radix Salviae Miltiorrhizae, Radix Notoginseng are through using water extraction twice respectively, and each 1 hour, merge extractive liquid, concentrated, and gets Radix Salviae Miltiorrhizae extract, Radix Notoginseng extract; An amount of dissolve with ethanol of Borneolum Syntheticum is used beta-cyclodextrin inclusion compound;

Radix Salviae Miltiorrhizae extract, Radix Notoginseng extract are added the injection water make dissolving in right amount, boil, put coldly, filter, filtrate is mixed with Borneolum Syntheticum β-CDBao He solution, and with mannitol, it is an amount of to add water for injection, accent pH, and lyophilizing, promptly.

Algoscopy is got 5 bottles of this product, and inclining content, mixing, precision takes by weighing in right amount (being equivalent to 1 bottle amount approximately), in the 25ml measuring bottle, after the water 5ml dissolving, be diluted to scale with dehydrated alcohol, shake up, precision is measured 0.5ml in the 10ml measuring bottle again, be diluted to scale with dehydrated alcohol behind the accurate adding inner mark solution 1ml, shake up, filter, draw subsequent filtrate 1ul, inject gas chromatograph is measured, and this product contains Borneolum Syntheticum with dextro Borneolum Syntheticum (C ₁₀H ₁₈O) meter, content is 6.25～15.0mg/g lyophilized powder solid content.

Above-mentioned compound red sage root freezing-dried powder injection adopts following method to measure salvianolic acid B (C in the freeze-dried powder ₃₆H ₃₀O ₁₆) content, its content assaying method is as follows:

Measure according to high performance liquid chromatography (" an appendix VI of Chinese pharmacopoeia version in 2005 D);

Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica, are mobile phase with acetonitrile-0.1% phosphoric acid (24: 76); The detection wavelength is 288nm; Number of theoretical plate calculates by the salvianolic acid B peak should be not less than 3000;

The preparation of reference substance solution: it is an amount of that precision takes by weighing the salvianolic acid B reference substance, adds methanol and make the solution that every 1ml contains 0.15mg, shakes up, promptly.

The preparation of need testing solution: get this product content under the content uniformity item, mixing is got 0.15g, accurate claims surely, puts in the 50ml measuring bottle, is dissolved in water and is diluted to scale, shakes up, and microporous filter membrane (0.45um) filters, promptly;

Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, contain Radix Salviae Miltiorrhizae with salvianolic acid B (C ₃₆H ₃₀O ₁₆) meter, content is 6.25～25.00mg/g lyophilized powder solid content.

In the above-mentioned compound lyophilized powder, Radix Salviae Miltiorrhizae is with danshensu (C ₉H ₁₀O ₅) meter, according to the content of danshensu in high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 D) the mensuration freeze-dried powder;

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Acetonitrile-0.1% phosphoric acid (8: 92) is mobile phase; The detection wavelength is 280nm; Number of theoretical plate calculates by the danshensu sodium peak should be not less than 3000;

The preparation of reference substance solution: it is an amount of that precision takes by weighing the danshensu sodium reference substance, adds methanol and make the solution that every 1ml contains 0.1mg, shakes up, promptly;

The preparation of need testing solution: get this product content under the content uniformity item, mixing is got 0.4g, accurate claims surely, puts in the 25ml measuring bottle, is dissolved in water and is diluted to scale, shakes up, and microporous filter membrane (0.45um) filters, promptly;

Algoscopy: accurate reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, calculate, Radix Salviae Miltiorrhizae is with danshensu (C ₉H ₁₀O ₅) meter, content is 1.25～18.75mg/g lyophilized powder solid content.

The linear gradient elution proportion of mobile phase changes program

This product contains Radix Notoginseng with ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 three's total amount meter, content is 18.75～56.25mg/g lyophilized powder solid content.

Embodiment 2:

A. get recipe quantity Radix Salviae Miltiorrhizae 4000g, Radix Notoginseng 260g, Borneolum Syntheticum 50g is standby;

B. above Radix Salviae Miltiorrhizae, Radix Notoginseng get Radix Salviae Miltiorrhizae extract, Radix Notoginseng extract through using ethanol extraction respectively; An amount of dissolve with ethanol of Borneolum Syntheticum is used beta-cyclodextrin inclusion compound;

Measure content according to embodiment 1 content of bornyl alcohol assay method, this product contains Borneolum Syntheticum with dextro Borneolum Syntheticum (C ₁₀H ₁₈O) meter, content is 30.25～75.0mg/g lyophilized powder solid content.

Measure content according to embodiment 1 content of danshinolic acid B assay method, this product contains salvianolic acid B (C ₃₆H ₃₀O ₁₆) be 30.25～55.00mg/g lyophilized powder solid content.

According to embodiment 1 danshensu (C ₉H ₁₀O ₅) content assaying method mensuration content, this product contains danshensu (C ₉H ₁₀O ₅) be 5.25～38.75mg/g lyophilized powder solid content.

According to embodiment 1 ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 content assaying method measure content, this product contains ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 three's total amount is 8.3～26.5mg/g lyophilized powder solid content.

Embodiment 3:

A. get Radix Salviae Miltiorrhizae 1200g, Radix Notoginseng 300g, Borneolum Syntheticum 6g is standby;

B. above Radix Salviae Miltiorrhizae, Radix Notoginseng be through carrying through water respectively, 3 precipitate with ethanol, merge extractive liquid, concentrates, Radix Salviae Miltiorrhizae extract, Radix Notoginseng extract; An amount of dissolve with ethanol of Borneolum Syntheticum is used beta-cyclodextrin inclusion compound;

Radix Salviae Miltiorrhizae extract, Radix Notoginseng extract are added the injection water make dissolving in right amount, boil, put coldly, filter, filtrate is mixed with Borneolum Syntheticum β-CDBao He solution, and with mannitol, it is an amount of to add water for injection, accent pH, and lyophilizing is made 1000 bottles, promptly.

Measure content according to embodiment 1 method, this product contains Radix Notoginseng with ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), the total amount meter of ginsenoside Rb1, arasaponin R1, content is 11.5～24.2mg/g lyophilized powder solid content.

Embodiment 4

A. get Radix Salviae Miltiorrhizae 1500g, Radix Notoginseng 550g, Borneolum Syntheticum 20g is standby;

B. above Radix Salviae Miltiorrhizae water extraction twice adds 8 times of water gagings and extracted 3 hours the first time, adds 6 times of water gagings for the second time and extracts 2 hours, and merge extractive liquid, concentrates, and gets Radix Salviae Miltiorrhizae extract; Radix Notoginseng alcohol extraction twice adds 8 times of amount 85% ethanol extractions 2 hours the first time, adds 6 times of amount ethanol extractions 1 hour for the second time, and merge extractive liquid, concentrates, and gets Radix Notoginseng extract; An amount of dissolve with ethanol of Borneolum Syntheticum is used beta-cyclodextrin inclusion compound;

Radix Salviae Miltiorrhizae extract, Radix Notoginseng extract or Salvia miltiorrhiza and Panax notoginseng extract are added injection water 500ml make dissolving, boiled 5 minutes, put coldly, filter, filtrate is mixed with Borneolum Syntheticum β-CDBao He solution, with mannitol 10g, add water for injection and supply 1000ml in right amount, transferring pH is 5～7, lyophilizing, make 1000 bottles, promptly.

According to embodiment 1 ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 content assaying method measure content, this product contains ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 always be 18.5～42.2mg/g lyophilized powder solid content.

Embodiment 5

A. get Radix Salviae Miltiorrhizae 1400g, Radix Notoginseng 350g, Borneolum Syntheticum 30g is standby;

B. above Radix Salviae Miltiorrhizae water extraction three times adds 8 times of water gagings and extracted 2 hours the first time, adds 6 times of water gagings for the second time and extracts 1 hour, and add 4 times of water gagings for the third time and extracted 1 hour, merge extractive liquid,, precipitate with ethanol, solution concentration gets Radix Salviae Miltiorrhizae extract; Radix Notoginseng alcohol extraction three times adds 6 times for the first time and measured 80% ethanol extractions 2 hours, adds 6 times of amount 70% ethanol extractions 1 hour for the second time, adds 4 times of amount 60% ethanol extractions 1 hour for the third time, and merge extractive liquid, concentrates, and gets Radix Notoginseng extract; An amount of dissolve with ethanol of Borneolum Syntheticum is used beta-cyclodextrin inclusion compound;

Radix Salviae Miltiorrhizae extract, Radix Notoginseng extract or Salvia miltiorrhiza and Panax notoginseng extract are added injection water 300ml make dissolving, boiled 10 minutes, put coldly, filter, filtrate is mixed with Borneolum Syntheticum β-CDBao He solution, with mannitol 60g, add water for injection and supply 1000ml in right amount, transferring pH is 5～6.5, lyophilizing, make 1000 bottles, promptly.

Measure content according to embodiment 1 method, this product contains Radix Notoginseng with ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), the total amount meter of ginsenoside Rb1, arasaponin R1, content is 11.5～33.2mg/g lyophilized powder solid content.

According to embodiment 1 salvianolic acid B (C ₃₆H ₃₀O ₁₆) content assaying method mensuration content, this product contains salvianolic acid B (C ₃₆H ₃₀O ₁₆) be 10.25～25.00mg/g lyophilized powder solid content.

Embodiment 6

A. get Radix Salviae Miltiorrhizae 3500g, Radix Notoginseng 400g, Borneolum Syntheticum 8g is standby;

B. above three flavors, Radix Salviae Miltiorrhizae adds 8 times of water gagings and decocts, collecting decoction, and concentrate, concentrated solution adds 60% ethanol, leaves standstill, and filters, and filtrate concentrates, concentrated solution adds 70% ethanol, leaves standstill, and filters, and filtrate concentrates, add water, filter, filtrate concentrates, add 80% ethanol, leave standstill, filter, filtrate concentrates, and drying gets Radix Salviae Miltiorrhizae extract;

Radix Notoginseng adds 4 times of water gagings and decocts, and collecting decoction concentrates, and adds ethanol, leaves standstill, filter, filtrate concentrates, and adds water, and cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, reuse 85% ethanol elution is collected ethanol elution, is concentrated into thick paste, and drying gets Radix Notoginseng extract; Get HP-, add water, heating makes dissolving, adds active carbon and boils, and takes off charcoal, filtrate for later use; With an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution, enclose filters, and gets Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution;

Radix Salviae Miltiorrhizae extract and Radix Notoginseng extract are added injection water 200ml respectively make dissolving, boil, put and be chilled to room temperature, cold preservation filters, and filtrate merges, add active carbon, charcoal is taken off in insulation, mix with Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution filtrate cooling back, with mannitol, adds water for injection in right amount to 1000ml, transfer pH5～5.5, lyophilizing is made 1000 bottles, promptly.

According to embodiment 1 ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 content assaying method measure content, this product contains ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 be 19.5～31.2mg/g lyophilized powder solid content.

According to embodiment 1 dextro Borneolum Syntheticum (C ₁₀H ₁₈O) content assaying method is measured content, and this product contains Borneolum Syntheticum with dextro Borneolum Syntheticum (C ₁₀H ₁₈O) meter, content is 6.25～14.8mg/g lyophilized powder solid content.

Embodiment 7

A. get Radix Salviae Miltiorrhizae 2000g, Radix Notoginseng 450g, Borneolum Syntheticum 30g is standby;

B. above three flavors, Radix Salviae Miltiorrhizae adds 6 times of water gagings and decocts 2 times, and each 1 hour, collecting decoction, and concentrate, concentrated solution adds 85% ethanol, leaves standstill, and filters, filtrate concentrates, and concentrated solution adds 80% ethanol, leaves standstill, and filters, filtrate concentrates, and adds water, filters, and filtrate concentrates, add 80% ethanol, leave standstill, filter, filtrate concentrates, and drying gets Radix Salviae Miltiorrhizae extract;

Radix Notoginseng adds 7 times of water gagings and decocts, and collecting decoction concentrates, and adds 75% ethanol, leaves standstill, filter, filtrate concentrates, and adds water, and cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, reuse 75% ethanol elution is collected ethanol elution, is concentrated into thick paste, and drying gets Radix Notoginseng extract; Get HP-, add water, heating makes dissolving, adds active carbon and boils, and takes off charcoal, filtrate for later use; With an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution, enclose filters, and gets Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution;

Radix Salviae Miltiorrhizae extract and Radix Notoginseng extract are added injection water 250ml respectively make dissolving, boil, put and be chilled to room temperature, cold preservation filters, and filtrate merges, add active carbon, charcoal is taken off in insulation, mix with Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution filtrate cooling back, with mannitol, adds water for injection 1500ml, transfer pH4～5, lyophilizing is made 1000 bottles, promptly.

According to embodiment 1 ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 content assaying method measure content, this product contains ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 be 18.5～34.8mg/g lyophilized powder solid content.

According to embodiment 1 salvianolic acid B (C ₃₆H ₃₀O ₁₆) content assaying method mensuration content, this product contains salvianolic acid B (C ₃₆H ₃₀O ₁₆) be 20.25～30.10mg/g lyophilized powder solid content.

Embodiment 8

A. get Radix Salviae Miltiorrhizae 1800g, Radix Notoginseng 260g, Borneolum Syntheticum 10g is standby;

B. above three flavors, Radix Salviae Miltiorrhizae adds 5 times of water gagings and decocts 2 times, and each 2 hours, collecting decoction, and concentrate, concentrated solution adds 75% ethanol, leaves standstill, and filters, filtrate concentrates, and concentrated solution adds 80% ethanol, leaves standstill, and filters, filtrate concentrates, and adds water, filters, and filtrate concentrates, add 80% ethanol, leave standstill, filter, filtrate concentrates, and drying gets Radix Salviae Miltiorrhizae extract;

Radix Notoginseng adds 8 times of water gagings and decocts, and collecting decoction concentrates, and adds 85% ethanol, leaves standstill, filter, filtrate concentrates, and adds water, and cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, reuse 85% ethanol elution is collected ethanol elution, is concentrated into thick paste, and drying gets Radix Notoginseng extract; Get HP-, add water, heating makes dissolving, adds active carbon and boils, and takes off charcoal, filtrate for later use; With an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution, enclose filters, and gets Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution;

Radix Salviae Miltiorrhizae extract and Radix Notoginseng extract are added injection water 450ml respectively make dissolving, boil, put and be chilled to room temperature, cold preservation filters, and filtrate merges, add active carbon, charcoal is taken off in insulation, mix with Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution filtrate cooling back, with mannitol, adds water for injection 2000ml, transfer pH4～6, lyophilizing is made 1000 bottles, promptly.

According to embodiment 1 ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 content assaying method measure content, this product contains ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 be 9.5～25.4mg/g lyophilized powder solid content.

According to embodiment 1 salvianolic acid B (C ₃₆H ₃₀O ₁₆) content assaying method mensuration content, this product contains salvianolic acid B (C ₃₆H ₃₀O ₁₆) be 25.25～36.40mg/g lyophilized powder solid content.

Embodiment 9

A. get Radix Salviae Miltiorrhizae 3000g, Radix Notoginseng 360g, Borneolum Syntheticum 15 is standby;

B. above three flavors, the Radix Salviae Miltiorrhizae section decocts with water each 1 hour 5 times, collecting decoction, and be concentrated into the extractum that relative density is 1.05～1.35 (50 ℃) adds ethanol and makes and contain the alcohol amount and reach 85%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adding ethanol makes and contains the alcohol amount and reach 85%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.15～1.45 (50 ℃), add 4 times of water gagings, cold preservation filters, and filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adding ethanol makes and contains the alcohol amount and reach 90%, leave standstill, filter, filtrate is concentrated into thick paste, drying gets Radix Salviae Miltiorrhizae extract;

Get Radix Notoginseng, decoct with water 5 times, each 1 hour, collecting decoction, and be concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), and add ethanol and make and contain the alcohol amount and reach 90%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adds 10 times of water gagings, cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, reuse 85% ethanol elution is collected ethanol elution, be concentrated into thick paste, drying gets Radix Notoginseng extract;

Get HP-1500g, add water in right amount, heating makes dissolving, adds 1% active carbon and boils 60 minutes, takes off charcoal, filtrate for later use; With an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution, ultrasonic enclose 2 hours filters, and gets Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution;

Radix Salviae Miltiorrhizae extract and Radix Notoginseng extract are added the injection water respectively make dissolving in right amount, boiled 20 minutes, put and be chilled to room temperature, cold preservation filters, and filtrate merges, add 90 ℃ of insulations of 0.2% active carbon 60 minutes, take off charcoal, filtrate is cooled to back below 70 ℃ and mixes with Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution, with mannitol 300g, add water for injection to an amount of, transferring pH is 5～7, lyophilizing, make 1000 bottles, promptly.

According to embodiment 1 ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 content assaying method measure content, this product contains ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), ginsenoside Rb1, arasaponin R1 be 16.5～38.2mg/g lyophilized powder solid content.

According to embodiment 1 danshensu (C ₉H ₁₀O ₅) content assaying method mensuration content, this product contains danshensu (C ₉H ₁₀O ₅) be 5.5～8.8mg/g lyophilized powder solid content.

Embodiment 10

A. get Radix Salviae Miltiorrhizae 3000g, Radix Notoginseng 850g, Borneolum Syntheticum 35 is standby;

B. above three flavors, the Radix Salviae Miltiorrhizae section decocts with water each 2 hours 3 times, collecting decoction, and be concentrated into the extractum that relative density is 1.05～1.35 (50 ℃) adds ethanol and makes and contain the alcohol amount and reach 50%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adding ethanol makes and contains the alcohol amount and reach 85%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.15～1.45 (50 ℃), add 2 times of water gagings, cold preservation filters, and filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adding ethanol makes and contains the alcohol amount and reach 50%, leave standstill, filter, filtrate is concentrated into thick paste, drying gets Radix Salviae Miltiorrhizae extract;

Get Radix Notoginseng, decoct with water 3 times, each 1 hour, collecting decoction, and be concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), and add ethanol and make and contain the alcohol amount and reach 50%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adds 2 times of water gagings, cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, reuse 50% ethanol elution is collected ethanol elution, be concentrated into thick paste, drying gets Radix Notoginseng extract;

Get HP-100g, add water in right amount, heating makes dissolving, adds 0.2% active carbon and boils 5 minutes, takes off charcoal, filtrate for later use.With an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution, ultrasonic enclose 1～12 hour filters, and gets Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution;

Radix Salviae Miltiorrhizae extract and Radix Notoginseng extract are added the injection water respectively make dissolving in right amount, boiled 1～20 minute, put and be chilled to room temperature, cold preservation filters, and filtrate merges, add 50 ℃ of insulations of 0.05% active carbon 10 minutes, take off charcoal, filtrate is cooled to back below 70 ℃ and mixes with Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution, with mannitol 20g, add water for injection to an amount of, transferring pH is 5～7, lyophilizing, make 1000 bottles, promptly.

In the above-mentioned compound lyophilized powder, Radix Notoginseng is with the ginsenoside Rg1, the ginsenoside Rb1, and arasaponin R1 content meter, content is measured according to high performance liquid chromatography (" an appendix VI of Chinese pharmacopoeia version in 2005 D).

1, instrument and reagent

Instrument high performance liquid chromatograph: Waters 600E pump, 717 automatic samplers, Waters PDA2996 diode array detector; Waters Empower chromatographic work station; Mettler AE240 (100,000/) balance (prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit Shanghai Instr Ltd.); High purity water distillator (Xinda, Jiangsu instrument plant) boils in SYZ-A quartz Asia.

The reagent ginsenoside Rg1 is available from Chinese medicine bioassay institute (lot number 0703-200015 uses for containing to survey)

The ginsenoside Rb1 is available from Chinese biological drug inspection office (lot number 0704-200012 uses for containing to survey).

Arasaponin R1 is available from Chinese biological drug inspection office lot number (lot number 0745-200012 uses for containing to survey).

Acetonitrile is a chromatographically pure; Finished product sample and negative control product (providing) by our company.

2, the selection of chromatographic condition

Chromatographic column: Diamonsil C ₁₈, 5 μ m, 250 * 4.6mm (Di Ma company product); Mobile phase: acetonitrile-water linear gradient elution (as following table); Column temperature: 30 ℃; Flow velocity 1ml/min; Detect wavelength: 203nm (from Fig. 4-6 as can be seen, their absorption maximum is at 203nm, so select this wavelength).Under this chromatographic condition, the ginsenoside Rg1 separates well with other component in the sample, number of theoretical plate by ginsenoside Rg1's reference substance peak greater than 2000.(seeing Fig. 4 ~ 10).

The linear gradient elution proportion of mobile phase changes program

3, the preparation of need testing solution

Get this product content under the content uniformity item, mixing is got 0.5g, accurate claims surely, puts in the 10ml measuring bottle, is dissolved in water and is diluted to scale, shakes up, and microporous filter membrane (0.45um) filters, promptly.

4, repeatability test

Precision takes by weighing 5 parts in sample, and (lot number: 030307), every part of about 0.5g presses the operation of need testing solution preparation method, and sample introduction is measured in accordance with the law, calculates content, asks relative standard deviation RSD.The result shows that this law is measured has good repeatability, the results are shown in Table 1.

Table 1 ginsenoside Rg1, ginsenoside Rb1, the test of arasaponin R1 repeatability

Embodiment 11

A. get Radix Salviae Miltiorrhizae 2469.85g, Radix Notoginseng 425.25g, Borneolum Syntheticum 25.25 is standby;

B. above three flavors, the Radix Salviae Miltiorrhizae section decocts with water each 1.5 hours 2 times, collecting decoction, and be concentrated into the extractum that relative density is 1.05～1.35 (50 ℃) adds ethanol and makes and contain the alcohol amount and reach 75%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adding ethanol makes and contains the alcohol amount and reach 65%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.15～1.45 (50 ℃), add 10 times of water gagings, cold preservation filters, and filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adding ethanol makes and contains the alcohol amount and reach 70%, leave standstill, filter, filtrate is concentrated into thick paste, drying gets Radix Salviae Miltiorrhizae extract;

Get Radix Notoginseng, decoct with water 2 times, each 1.5 hours, collecting decoction, and be concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), and add ethanol and make and contain the alcohol amount and reach 70%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adds 6 times of water gagings, cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, reuse 65% ethanol elution is collected ethanol elution, be concentrated into thick paste, drying gets Radix Notoginseng extract;

Get HP-200g, add water in right amount, heating makes dissolving, adds 0.5% active carbon and boils 30 minutes, takes off charcoal, filtrate for later use; With an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution, ultrasonic enclose 4 hours filters, and gets Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution;

Radix Salviae Miltiorrhizae extract and Radix Notoginseng extract are added the injection water respectively make dissolving in right amount, boiled 15 minutes, put and be chilled to room temperature, cold preservation filters, and filtrate merges, add 70 ℃ of insulations of 0.1% active carbon 20 minutes, take off charcoal, filtrate is cooled to back below 60 ℃ and mixes with Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution, with mannitol 40g, add water for injection to an amount of, transferring pH is 5～7, lyophilizing, make 1000 bottles, promptly.

Measure content according to embodiment 11 methods, this product contains the ginsenoside Rg ₁(C ₂₇H ₃₂O ₁₆) 6.5～15.5mg/ bottle freeze-dried powder solid content, ginsenoside Rb ₁7.2～13.5mg/ bottle freeze-dried powder solid content, Panax Notoginseng saponin R ₁0.95～4.25mg/g freeze-dried powder solid content.

According to embodiment 1 salvianolic acid B (C ₃₆H ₃₀O ₁₆) content assaying method mensuration content, this product contains salvianolic acid B (C ₃₆H ₃₀O ₁₆) be 18.25～29.55mg/g lyophilized powder solid content.

Embodiment 12

A. get Radix Salviae Miltiorrhizae 2266.2g, Radix Notoginseng 438.2g, natural Broneolum Syntheticum 20.6g is standby;

B. above three flavors, Radix Salviae Miltiorrhizae adds 8 times of water gagings, second for the first time, add 6 times of water gagings for three times respectively, decocted 1 hour at every turn, collecting decoction, and be concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), and add ethanol and make and contain the alcohol amount and reach 65%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adds ethanol and makes and contain the alcohol amount and reach 65%, leaves standstill, filter, filtrate is concentrated into the extractum that relative density is 1.15～1.45 (50 ℃), adds 8 times of water gagings, cold preservation, filter, filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adds ethanol and makes and contain the alcohol amount and reach 80%, leaves standstill, filter, filtrate is concentrated into thick paste, and drying gets Radix Salviae Miltiorrhizae extract;

Get Radix Notoginseng, add 6 times of water gagings and decoct 3 times, each 1 hour, collecting decoction, and be concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), and add ethanol and make and contain the alcohol amount and reach 60%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adds 6 times of water gagings, cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, reuse 65% ethanol elution is collected ethanol elution, be concentrated into thick paste, drying gets Radix Notoginseng extract;

Get HP-150g, add water in right amount, heating makes dissolving, adds 0.4% active carbon and boils 20 minutes, takes off charcoal, filtrate for later use; With an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution, ultrasonic enclose 2 hours filters, and gets Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution;

Radix Salviae Miltiorrhizae extract and Radix Notoginseng extract are added the injection water respectively make dissolving in right amount, boiled 10 minutes, put and be chilled to room temperature, cold preservation filters, and filtrate merges, add 70 ℃ of insulations of 0.01% active carbon 10 minutes, take off charcoal, filtrate is cooled to back below 70 ℃ and mixes with Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution, with mannitol 80g, add water for injection to an amount of, transferring pH is 5～7, lyophilizing, make 1000 bottles, promptly.

Measure content according to embodiment 11 methods, this product contains the ginsenoside Rg ₁(C ₂₇H ₃₂O ₁₆) 7.5～13.5mg/ bottle freeze-dried powder solid content, ginsenoside Rb ₁7.9～15.5mg/ bottle freeze-dried powder solid content, Panax Notoginseng saponin R ₁1.36～4.05mg/g freeze-dried powder solid content.

According to embodiment 1 danshensu (C ₉H ₁₀O ₅) content assaying method mensuration content, this product contains danshensu (C ₉H ₁₀O ₅) be 3.9～10.5mg/g lyophilized powder solid content.

Embodiment 13

A. get Radix Salviae Miltiorrhizae 2486.2g, Radix Notoginseng 486.2g, natural Broneolum Syntheticum 27.6g is standby;

B. above three flavors, Radix Salviae Miltiorrhizae adds 8 times of water gagings, second for the first time, add 6 times of water gagings for three times respectively, decocted 1 hour at every turn, collecting decoction, and be concentrated into the extractum that relative density is about 1.15 (50 ℃), and add ethanol and make and contain the alcohol amount and reach 75%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is about 1.15 (50 ℃), adds ethanol and makes and contain the alcohol amount and reach 85%, leaves standstill, filter, filtrate is concentrated into the extractum that relative density is about 1.25 (50 ℃), adds 8～10 times of water gagings, cold preservation, filter, filtrate is concentrated into the extractum that relative density is about 1.15 (50 ℃), adds ethanol and makes and contain the alcohol amount and reach 80%, leaves standstill, filter, filtrate is concentrated into thick paste, and drying gets Radix Salviae Miltiorrhizae extract;

Get Radix Notoginseng powder and be broken into granule, add 8 times of water gagings and decoct three times, each 1 hour, collecting decoction, and be concentrated into the extractum that relative density is about 1.15 (50 ℃), and add ethanol and make and contain the alcohol amount and reach 80%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is about 1.15 (50 ℃), adds 3～5 times of water gagings, cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, reuse 70% ethanol elution is collected 70% ethanol elution, be concentrated into thick paste, drying gets Radix Notoginseng extract;

Get HP-500g, add water to 1500ml, heating makes dissolving, adds 0.5% active carbon and boils 20 minutes, takes off charcoal, filtrate for later use.With an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution, ultrasonic enclose 6 hours filters, and gets Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution;

Radix Salviae Miltiorrhizae extract and Radix Notoginseng extract are added the injection water respectively make dissolving in right amount, boiled 10 minutes, put and be chilled to room temperature, cold preservation, filter, filtrate merges, and adds 80 ℃ of insulations of 0.1% active carbon 30 minutes, take off charcoal, filtrate is cooled to back below 50 ℃ mixes with Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution, with mannitol 100g, add water for injection to 4000ml, transferring pH is 6.5, and degerming filters, in fill to the 1000 bottle cillin bottle, add butyl rubber bung, lyophilizing, gland, check, packing is promptly.

Measure content according to embodiment 11 methods, this product contains the ginsenoside Rg ₁(C ₂₇H ₃₂O ₁₆), ginsenoside Rb ₁, Panax Notoginseng saponin R ₁See Table 2.

Table 2 ginsenoside Rg1, ginsenoside Rb1, the test of arasaponin R1 repeatability

According to embodiment 1 dextro Borneolum Syntheticum (C ₁₀H ₁₈O) content assaying method is measured content, and this product contains dextro Borneolum Syntheticum (C ₁₀H ₁₈O) be 31.25～41.5mg/g lyophilized powder solid content.

According to embodiment 1 salvianolic acid B (C ₃₆H ₃₀O ₁₆) content assaying method mensuration content, this product contains salvianolic acid B (C ₃₆H ₃₀O ₁₆) be 25.00～30.10mg/g lyophilized powder solid content.

According to embodiment 1 danshensu (C ₉H ₁₀O ₅) content assaying method mensuration content, this product contains danshensu (C ₉H ₁₀O ₅) be 3.5～9.85mg/g lyophilized powder solid content.

Embodiment 14

A. get Radix Salviae Miltiorrhizae 2468.2g, Radix Notoginseng 468.2g, natural Broneolum Syntheticum 27.6g is standby;

B. above three flavors, the Radix Salviae Miltiorrhizae section decocts with water each 0.5 hour 3 times, collecting decoction, and be concentrated into the extractum that relative density is 1.05～1.35 (50 ℃) adds ethanol and makes and contain the alcohol amount and reach 75%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adding ethanol makes and contains the alcohol amount and reach 85%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.15～1.45 (50 ℃), add 4 times of water gagings, cold preservation filters, and filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adding ethanol makes and contains the alcohol amount and reach 85%, leave standstill, filter, filtrate is concentrated into thick paste, drying gets Radix Salviae Miltiorrhizae extract;

Get Radix Notoginseng, add 6 times of water gagings and decoct 3 times, each 0.5～3 hour, collecting decoction, and be concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), and add ethanol and make and contain the alcohol amount and reach 50～90%, leave standstill, filter, filtrate is concentrated into the extractum that relative density is 1.05～1.35 (50 ℃), adds 5 times of water gagings, cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, reuse 75% ethanol elution is collected ethanol elution, be concentrated into thick paste, drying gets Radix Notoginseng extract;

Get HP-200g, add water in right amount, heating makes dissolving, adds 1% active carbon and boils 50 minutes, takes off charcoal, filtrate for later use; With an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution, ultrasonic enclose 8 hours filters, and gets Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution;

Radix Salviae Miltiorrhizae extract and Radix Notoginseng extract are added the injection water respectively make dissolving in right amount, boiled 5 minutes, put and be chilled to room temperature, cold preservation filters, and filtrate merges, add 60 ℃ of insulations of 0.08% active carbon 25 minutes, take off charcoal, filtrate is cooled to back below 70 ℃ and mixes with Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution, with mannitol 150g, add water for injection to an amount of, transferring pH is 5～7, lyophilizing, make 1000 bottles, promptly.

Measure content according to embodiment 11 methods, this product contains the ginsenoside Rg ₁(C ₂₇H ₃₂O ₁₆) 8.012 ± 1.35mg/ bottle freeze-dried powder solid content, ginsenoside Rb ₁8.122 ± 1.45mg/ bottle freeze-dried powder solid content, Panax Notoginseng saponin R ₁2.049 ± 1.03mg/g freeze-dried powder solid content.

According to embodiment 1 danshensu (C ₉H ₁₀O ₅) content assaying method mensuration content, this product contains danshensu (C ₉H ₁₀O ₅) be 3.2～8.85mg/g lyophilized powder solid content.

Claims

1. compound red sage root freezing-dried powder injection, be to make: Radix Salviae Miltiorrhizae 2000～3000g, Radix Notoginseng 360～550g, Borneolum Syntheticum 15～35g by following raw materials in part by weight, wherein Radix Notoginseng is in the total amount of ginsenoside Rg1, ginsenoside Rb1, arasaponin R1, and content is 18.75～31.25mg/g lyophilized powder solid content; Radix Salviae Miltiorrhizae is in danshensu, and content is 3.75～12.75mg/g lyophilized powder solid content; Radix Salviae Miltiorrhizae is in salvianolic acid B, and content is 25.0～50.125mg/g lyophilized powder solid content; Borneolum Syntheticum is in dextro Borneolum Syntheticum, and content is 25.0～50.25mg/g lyophilized powder solid content, and the preparation method of described lyophilized injectable powder comprises the steps:

A. Radix Salviae Miltiorrhizae, Radix Notoginseng, the Borneolum Syntheticum of getting above-mentioned consumption are standby;

B. above three flavors, the Radix Salviae Miltiorrhizae section decocts with water each 0.5～3 hour 1～5 time, collecting decoction, and the extractum of relative density 1.05～1.35 when being concentrated into 50 ℃ add ethanol and make and contain the alcohol amount and reach 50～85%, leave standstill, filter, relative density was 1.05～1.35 extractum when filtrate was concentrated into 50 ℃, adding ethanol makes and contains the alcohol amount and reach 85%, leave standstill, filter, relative density was 1.15～1.45 extractum when filtrate was concentrated into 50 ℃, add 2～14 times of water gagings, cold preservation filters, and relative density was 1.05～1.35 extractum when filtrate was concentrated into 50 ℃, adding ethanol makes and contains the alcohol amount and reach 50～90%, leave standstill, filter, filtrate is concentrated into thick paste, drying gets Radix Salviae Miltiorrhizae extract; Get Radix Notoginseng, decoct with water 1～5 time, each 0.5～3 hour, collecting decoction, and relative density is 1.05～1.35 extractum when being concentrated into 50 ℃, adds ethanol and makes and contain the alcohol amount and reach 50～90%, leaves standstill, filter, relative density was 1.05～1.35 extractum when filtrate was concentrated into 50 ℃, added 1～10 times of water gaging, cold preservation filters, and filtrate is by behind the macroporous adsorptive resins, wash with water earlier, reuse 50～85% ethanol elutions are collected ethanol elution, be concentrated into thick paste, drying gets Radix Notoginseng extract; Get HP-100～1500g, add water to an amount of, heating makes dissolving, adds 0.2～1% active carbon and boils 5～60 minutes, takes off charcoal, filtrate for later use, with an amount of dissolve with ethanol of Borneolum Syntheticum, slowly drop in the HP-aqueous solution ultrasonic enclose 1～12 hour, filter, get Borneolum Syntheticum hydroxy propyl-Beta-CD enclose solution;

2. compound red sage root freezing-dried powder injection according to claim 1 is characterized in that wherein Radix Notoginseng is with ginsenoside Rg1 (C ₂₇H ₃₂O ₁₆), the total amount meter of ginsenoside Rb1, arasaponin R1, content is 18.75～25.0mg/g lyophilized powder solid content; Radix Salviae Miltiorrhizae is with danshensu (C ₉H ₁₀O ₅) meter, content is 3.75～8.875mg/g lyophilized powder solid content; Radix Salviae Miltiorrhizae is with salvianolic acid B (C ₃₆H ₃₀O ₁₆) meter, content is 25.0～41.375mg/g lyophilized powder solid content; Borneolum Syntheticum is with dextro Borneolum Syntheticum (C ₁₀H ₁₈O) meter, content is 31.25～41.5mg/g lyophilized powder solid content.