CN1600318A - Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease - Google Patents
Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease Download PDFInfo
- Publication number
- CN1600318A CN1600318A CN 03144310 CN03144310A CN1600318A CN 1600318 A CN1600318 A CN 1600318A CN 03144310 CN03144310 CN 03144310 CN 03144310 A CN03144310 A CN 03144310A CN 1600318 A CN1600318 A CN 1600318A
- Authority
- CN
- China
- Prior art keywords
- content
- peak
- total
- ginsenoside
- extract
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Abstract
A Chinese medicine for treating cardiovascular and cerebrovascular diseases is prepared from red sage root, notoginseng, borneol and dialbergia wood oil.
Description
Technical field
The present invention relates to a kind of medicinal preparation, more particularly, relate to a kind of Chinese medicine composition for the treatment of cardiovascular and cerebrovascular disease.
Background technology
According to China's Epidemiological study, though over nearly 50 years in the rural area or the city, the M ﹠ M of cardiovascular and cerebrovascular disease is all in rising trend.50～sixties, China's population cause of death central vessel disease and cerebrovascular occupied the five or six respectively, then rose to the two or three respectively later in 1975, and cardiovascular and cerebrovascular disease death person has accounted for first of whole disease cause of the death.China accounts for the percentage ratio of total dead population because of cardiovascular and cerebrovascular disease death person, rise to 42.6% of calendar year 2001 by 12.07% of nineteen fifty-seven, the person reaches 2,000,000 to die from the cardiovascular and cerebrovascular disease every year, though other has the part patient to survive through rescue, but majority stays deformity, can't take care of oneself, cause serious burden to relatives and society.Cardiovascular and cerebrovascular disease also is western countries crowd main causes of death.Infer that according to present existing epidemiologic data advancing of disease trend is: to the year two thousand twenty, the human diseases cause of the death puts in order will have great change, but coronary heart disease and apoplexy will be first and second of the human cause of the death.Till that time, estimate that global coronary heart disease death number will increase to 1,100 ten thousand from 6,300,000 of nineteen ninety; Apoplexy increases to 7,700,000 from 4,400,000.Blood circulation cause of the death formation will increase 59.6% in 30 years, and coronary heart disease and apoplexy increase 74.6% and 75% respectively.These data prove absolutely that cardiovascular and cerebrovascular disease is not only the principal disease of harm humans health, especially human " the No.1 killer " who causes death, disables at present and in following 20 years.
In the medicine of cardiovascular and cerebrovascular disease, the application of Chinese medicine and western medicine emphasizes particularly on different fields, and Chinese medicine also occupies the bigger market share with the little advantage of its side effect.In the Chinese patent medicine of present numerous treatment cardiovascular and cerebrovascular diseases, be that the Chinese patent medicine of main active such as Radix Notoginseng total arasaponins, Radix Salviae Miltiorrhizae total phenolic acids, Radix Puerariae flavone, Herb Gynostemmae Pentaphylli total glycosides etc. more and more is subject to people's attention with effective site.The effect of the various effective ingredient in Chinese of treatment cardiovascular and cerebrovascular disease is had nothing in common with each other and is stressed, and therefore, has the great demand of drug combination clinically.At present injection such as XUESAITONG, the XUESHUANTONG etc. of the herbal species, particularly effective ingredient in Chinese of each single effective site are difficult to satisfy the demand of clinical drug combination.In addition, with the mixed simply use of Chinese medicine, will emit huge risk, might cause unpredictable untoward reaction, sharply increase heating, anaphylaxis or the like as blood pressure without the approval of national drug food Surveillance Authority.Therefore, provide convenient effective effective ingredient in Chinese compound preparation to have the important clinical meaning.
Summary of the invention
The objective of the invention is in order to overcome the deficiency that single effective ingredient in Chinese is difficult to satisfy the demand for the treatment of the cardiovascular and cerebrovascular disease drug combination clinically, avoid medicine simply to mix the side reaction that use may cause, a kind of better efficacy clinically, convenient effective ingredient in Chinese compound and preparation thereof are provided.
The present invention is implemented by following technical proposals.
Chinese medicine composition of the present invention comprises following component by weight percentage:
Radix Salviae Miltiorrhizae extract 5.0%～80.0%
Radix Notoginseng extract 15.0%～93.0%
Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 2.0%～15.0%
Chinese medicine composition of the present invention is preferably and comprises following component by weight percentage:
Radix Salviae Miltiorrhizae extract 10.0%～68.0%
Radix Notoginseng extract 30.0%～88.0%
Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 2.0%～12.0%
Chinese medicine composition of the present invention more preferably comprises following component by weight percentage:
Radix Salviae Miltiorrhizae extract 25.0%～50.0%
Radix Notoginseng extract 40.0%～65.0%
Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 4.0%～10.0%
Chinese medicine composition of the present invention, best for comprising following component by weight percentage:
Radix Salviae Miltiorrhizae extract 30.3%
Radix Notoginseng extract 60.6%
Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 9.1%
Radix Salviae Miltiorrhizae extract in the above-mentioned Chinese medicine composition, can utilize the preparation method of prior art to obtain, for example can utilize Chinese patent application CN1352985A, CN1247855A, CN1242364A, CN1384090A, 02117923.9, (Yunnan University of Traditional Chinese Medicine's journal such as Guo Ying, 2001,24 (4): preparation method 6) obtains.Also can grope preparation technology voluntarily obtains.Content of danshinolic acid B is 45%～70% in the Radix Salviae Miltiorrhizae extract of the present invention, and salvianolic acid E content is 2～10%, and rosmarinic acid contents is 4%～20%, and alkannic acid content is 1%～10%, and its total phenolic content is preferably in more than 80% more than 70%.No matter be or groping preparation technology voluntarily prepares Radix Salviae Miltiorrhizae extract of the present invention,, then should make with extra care, make it to meet above-mentioned content standard if do not reach above-mentioned content standard by prior art.Its assay and finger printing are as follows:
(1) assay (high performance liquid chromatography) of salvianolic acid B, salvianolic acid E, rosmarinic acid, alkannic acid in the above-mentioned Radix Salviae Miltiorrhizae extract
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Acetonitrile-water-phosphoric acid (23.5: 76.5: 0.02) is mobile phase; The detection wavelength is 288nm.Number of theoretical plate is pressed the salvianolic acid B peak and is calculated, and should be not less than 5000.
The preparation precision of reference substance solution takes by weighing the salvianolic acid B reference substance, adds mobile phase and makes the solution that every 1ml contains 0.2mg; Salvianolic acid E is made the solution that every 1ml contains 0.02mg; Rosmarinic acid is made the solution that every 1ml contains 0.05mg; Alkannic acid is made the solution that every 1ml contains 0.01mg.
The preparation precision of need testing solution takes by weighing the about 35mg of this product, puts in the 25ml measuring bottle, adds the mobile phase dissolving and is diluted to scale, shakes up; Precision is measured 5ml and is put in the 25ml measuring bottle, is diluted to scale with mobile phase, shakes up, promptly.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
(2) mensuration (spectrophotography) of the total phenolic acid of above-mentioned Radix Salviae Miltiorrhizae extract
The preparation precision of reference substance solution takes by weighing the salvianolic acid B reference substance, makes the solution that every 1ml contains 20 μ g with acetonitrile-water-phosphoric acid (23.5: 76.5: 0.02) mixed solution, promptly.
The preparation precision of need testing solution takes by weighing the about 25mg of this product, puts in the 50ml measuring bottle, with acetonitrile-water-phosphoric acid (23.5: 76.5: 0.02) mixed solution dissolving and be diluted to scale, shake up, precision is measured 2ml, puts in the 50ml measuring bottle, add above-mentioned mixed solution and be diluted to scale, shake up, promptly.
Algoscopy is got reference substance solution and need testing solution respectively, is blank with acetonitrile-water-phosphoric acid (23.5: 76.5: 0.02), according to spectrophotography (1995 editions appendix VA of Chinese Pharmacopoeia), measures trap at 288nm wavelength place, is calculated as follows, promptly.
Total phenolic content (%)=f (A-B)+B
In the formula: f is a correction factor 0.626;
A is that spectrophotometry is the content of total phenolic acid of contrast calculating with the salvianolic acid B;
B is the content of the salvianolic acid B of high effective liquid chromatography for measuring.
(3) above-mentioned Radix Salviae Miltiorrhizae extract HPLC finger printing
Assay method is referring to the assay (high performance liquid chromatography) of salvianolic acid B, salvianolic acid E, rosmarinic acid, alkannic acid in (1) above-mentioned Radix Salviae Miltiorrhizae extract.The record chromatograph time is 60 minutes.
Adopting in the total fingerprint peaks the bigger and metastable total peak salvianolic acid B of peak area as the reference peak, is basic calculation relative retention time and relative peak area with the reference peak.The finger printing of above-mentioned Radix Salviae Miltiorrhizae extract should have 5～7 total peaks, is generally 6 total peaks.The relative retention time at 6 total peaks is followed successively by 0.55～0.65 (salvianolic acid E peak), 0.66～0.70 (rosmarinic acid peak), 0.71～0.79 (alkannic acid peak), 1 (salvianolic acid B), 1.03～1.12,1.21～1.30.In the total peak unimodal area account for total peak area greater than 20% have only salvianolic acid B peak (promptly with reference to the peak), the peak area at salvianolic acid B peak accounts for 57%～87% of total peak area, its relative peak area is 1; Relative retention time is that 0.66～0.70 total peak (being the rosmarinic acid peak) peak area accounts for 3%～18% of total peak area, and its relative peak area is 0.03～0.25.The non-total peak gross area is not more than 10% of total peak area.
Radix Notoginseng extract in the above-mentioned Chinese medicine composition, can utilize the preparation method of prior art to obtain, for example can utilize (foreign medical science plant amedica fascicles such as Chinese patent ZL1095363C, Chinese patent application CN1352985A, Qian Tianxiang, 1997,5), the preparation method of national ministry standard WS3-B-3590-2001 (Z) obtains Radix Notoginseng extract 12 (4)), Tang's light (Chinese patent medicine 1990,12 (8):.Also can grope preparation technology voluntarily and extract Radix Notoginseng extract.Can also directly buy Radix Notoginseng extract from the market, for example content is the Radix Notoginseng total arasaponins (wherein Rb1 〉=30%, Rg1 〉=20%, R1 〉=5%, HPLC measure) of 95% (UV mensuration).Arasaponin R1 content should be 2%～10% in the Radix Notoginseng extract of the present invention, ginsenoside Re's content should be 2%～6%, ginsenoside Rg1's content should be 15%～40%, ginsenoside Rb1's content should be 15%～40%, ginsenoside Rd's content should be 5%～12%, the content of its Radix Notoginseng total arasaponins should be preferably in more than 80% more than 70%.No matter be to buy, do not reach above-mentioned content standard, then should make with extra care, make it to meet above-mentioned content standard as purity by prior art for preparing or market.Its assay and finger printing are as follows:
(1) ginsenoside Re, ginsenoside Rd, arasaponin R1, ginsenoside Rg1, ginsenoside Rb1's assay (high performance liquid chromatography) in the above-mentioned Radix Notoginseng extract
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Column temperature: 40 ℃; Flow velocity: 0.7ml/min; The detection wavelength is 203nm; The mobile phase of gradient elution is as follows:
| Time | Water | The second eyeball |
| ????0 | ????70 | ????30 |
| ????10 | ????70 | ????30 |
| ????30 | ????10 | ????90 |
The preparation precision of reference substance solution takes by weighing reference substance, add methanol and make the solution that every 1ml contains the 0.2mg ginsenoside Re respectively, every 1ml contains 0.4mg ginsenoside Rd's solution, every 1ml contains the solution of 0.2mg ginsenoside R1, every 1ml contains the solution of 0.4mg Panax Notoginseng saponin R g1, and every 1ml contains 0.4mg ginsenoside Rb1's solution.
The preparation precision of need testing solution takes by weighing the about 20mg of this product, puts in the 50ml measuring bottle, adds the mobile phase dissolving and is diluted to scale, shakes up, promptly.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
(2) mensuration (spectrophotography) of Radix Notoginseng total arasaponins in the above-mentioned Radix Notoginseng extract
The preparation precision of standard curve takes by weighing panoxadiol 2.6mg, puts in the 10ml volumetric flask, uses methanol constant volume, shakes up.The accurate 5ml that draws puts in the 50ml measuring bottle, and methanol constant volume shakes up.Accurate contrast liquid 0.5,1.0,1.5,2.0,2.5, the 3.0ml of drawing, put respectively in the tool plug test tube, fling to solvent in the hot bath, put coldly, accurate freshly prepared 5% vanillin glacial acetic acid solution 0.2ml and the perchloric acid 0.8ml of adding heats 15min in 60 ℃ of water-baths, the ice bath cooling, the accurate respectively glacial acetic acid 5ml that adds, mixing is placed 10min.And get blank solution work blank under the similarity condition, measure trap, production standard curve at 550nm wavelength place.
The preparation of need testing solution and mensuration precision take by weighing this product 0.3g, put in the conical flask, add a small amount of moistening of water after, add water saturated n-butyl alcohol reflux, extract, 3 times (30,20,15ml), each one hour, merge n-butyl alcohol liquid, adding the saturated water of n-butyl alcohol washs on a small quantity, discard water liquid, be diluted to 100ml, shake up with water saturated n-butyl alcohol.The accurate 10ml that draws puts in the 50ml measuring bottle, adds water saturated n-butyl alcohol and is diluted to scale, shake up, the accurate 0.5ml that draws, water bath method is put cold, accurate freshly prepared 5% vanillin glacial acetic acid solution 0.2ml and the perchloric acid 0.8ml of adding, in 60 ℃ of water-baths, heat 15min, ice bath cooling, the accurate respectively glacial acetic acid 5ml that adds, mixing is placed 10min.Measure trap at 550nm wavelength place, calculate content according to standard curve.
(3) above-mentioned Radix Notoginseng extract HPLC finger printing
Assay method is referring to the assay (high performance liquid chromatography) of ginsenoside Re, ginsenoside Rd, arasaponin R1, ginsenoside Rg1, ginsenoside Rb1 in (1) above-mentioned Radix Notoginseng extract.The record chromatograph time is 30 minutes.
Adopting in the total fingerprint peaks the bigger and metastable total peak ginsenoside Rg1 of peak area as the reference peak, is basic calculation relative retention time and relative peak area with the reference peak.The finger printing of above-mentioned Radix Notoginseng extract should have 9～12 total peaks, is generally 11 total peaks.The relative retention time at 11 total peaks is followed successively by 0.77～0.85 (arasaponin R1 peak), 0.87～0.97 (ginsenoside Re peak), 1 (the ginsenoside Rg1 peak is promptly with reference to the peak), 2.58～2.67,0.68～2.76,2.77～2.81,2.82～2.91 (ginsenoside Rb1 peaks), 2.95～3.03,3.05～3.13,3.15～3.22 (ginsenoside Rd peaks), 3.24～3.91.In the total peak unimodal area account for total peak area greater than 20% ginsenoside Rg1 peak and ginsenoside Rb1 peak arranged.The peak area at ginsenoside Rg1 peak (promptly with reference to the peak) accounts for 20%～35% of total peak area, and its relative peak area is 1; The peak area at ginsenoside Rb1 peak accounts for 30%～50% of total peak area, and its relative peak area is 0.85～2.50; The peak area at arasaponin R1 peak accounts for 2%～8% of total peak area, and its relative peak area is 0.06～0.40; The peak area at ginsenoside Rd peak accounts for 5%～14% of total peak area, and its relative peak area is 0.14～0.70.The non-total peak gross area is not more than 10% of total peak area.
Borneolum Syntheticum in the above-mentioned Chinese medicine composition is artificial Borneolum Syntheticum or natural Broneolum Syntheticum.Available Camphora replaces Borneolum Syntheticum in the compositions.
Lignum Dalbergiae Odoriferae oil in the above-mentioned Chinese medicine composition is that Lignum Dalbergiae Odoriferae makes through water distillation or supercritical carbon dioxide extraction.
Chinese medicine composition of the present invention, the various dosage forms that can be mixed and made into adjuvant on any or more than one pharmaceuticss such as starch, dextrin, lactose, microcrystalline Cellulose, hydroxypropyl methylcellulose, Polyethylene Glycol, magnesium stearate, micropowder silica gel, xylitol, lactose, glucose, glycine, mannitol, glycine etc., for example, can be made into injection, tablet, slow releasing tablet, drop pill, granule, injectable powder, capsule, microgranule.Preferred dosage form is tablet, drop pill, injectable powder, capsule.Chinese medicine composition of the present invention is made injection, injectable powder, and total phenolic content is preferably in more than 80% in its Radix Salviae Miltiorrhizae extract, and total saponin content is preferably in more than 80% in the Radix Notoginseng extract.
Chinese medicine composition raw material sources of the present invention are easy to get, and are easy to industrialization; Can make various dosage forms as required, for clinical provide convenient, more effectively, the more controlled modern Chinese medicine of quality, for the patient brings more benefits, thereby produce the huge social benefit.
The present invention adopts the ferric chloride part to stick middle cerebral artery and causes the focal cerebral ischemia injury model, by mensuration, compared the treating cerebral ischemia that Chinese medicine composition of the present invention, Radix Salviae Miltiorrhizae total phenolic acids add Radix Notoginseng total arasaponins, Radix Salviae Miltiorrhizae total phenolic acids, Radix Notoginseng total arasaponins to rat model nervous symptoms and cerebral infarction scope.The result shows, Chinese medicine composition of the present invention has tangible treating cerebral ischemia, its curative effect is better than using separately Radix Salviae Miltiorrhizae total phenolic acids or Radix Notoginseng total arasaponins, also be better than Radix Salviae Miltiorrhizae total phenolic acids and add Radix Notoginseng total arasaponins, show that Chinese medicine composition of the present invention is that Radix Salviae Miltiorrhizae extract adds Radix Notoginseng extract and adds Borneolum Syntheticum, perhaps Radix Salviae Miltiorrhizae extract adds Radix Notoginseng extract and adds the Lignum Dalbergiae Odoriferae oil three and have stronger synergism.
Experimental example 1 several Chinese medicine extraction compositionss are to the influence of focal cerebral ischemia in rats
(1) experiment material
1, animal
The SD rat, male, body weight 180g～200g, the quality certification number: SCXK (capital) 2002-0003 is provided by Beijing Vital River Experimental Animals Technology Co., Ltd..
2, medicine and reagent
Be subjected to reagent: the Chinese medicine composition of embodiment one, the Chinese medicine composition of embodiment two, the Radix Salviae Miltiorrhizae total phenolic acids of embodiment one, the Radix Notoginseng extract of embodiment one, Lignum Dalbergiae Odoriferae oil, Borneolum Syntheticum.XUESAITONG is the commercially available prod, is produced by Kunming Medicine Group Stock Co., Ltd, and lot number is 20020922.03.
Reagent: red tetrazolium (TTC) is pale yellow powder, Beijing Ma Shi fine chemicals company limited product, lot number: 011102.
3, instrument: XTT stero microscope, Yunnan Optical Instruments Factory's product; AEG-220 type electronic analytical balance, Japanese Shimadzu company product; The desk-top dentistry car of 307-6, Shanghai Dental Medical Apparatus and Instrument Factory's product; HZQ-C air bath agitator, Dongming, Harbin Medical Instruments factory product.
(2) experimental technique and result
1, grouping and administration
Laboratory animal is by the body weight random packet.Each treated animal is all in postoperative sublingual vein administration in 30 minutes, postoperative 2 hours and 23 hours intraperitoneal injection secondaries.Each medicine all is diluted to desired concn with normal saline, and injected dose adopts the 0.4ml/100g body weight.
2, the middle cerebral artery thrombus model is made
The anesthesia of rats by intraperitoneal injection 10% chloral hydrate solution (350mg/kg); right arm reclining is fixed; make a curved incision at paropia and external auditory meatus line mid point, be about 1.5cm, pinch off temporalis and excision; expose temporal bone; under stero microscope, at the bone window that cheekbone and the close oral-lateral 1mm place of temporo squamosum joint make a diameter 2.5mm, clear up residue with dental burr; expose middle cerebral artery (between tractus olfactorius and inferior cerebral vein), put small pieces plastic sheeting protection blood vessel surrounding tissue.Have the small pieces quantitative filter paper of 50% ferric chloride solution, 10 μ L to apply on this section middle cerebral artery suction, take off filter paper behind the 30min, use the normal saline flushing local organization, layer-by-layer suture steams again and raises.Room temperature is controlled at 24 ℃.
3, nervous symptoms standards of grading
To experimental animal 24h after surgery, carry out behavior and detect.Standards of grading: 1. carry the Mus tail and observe forelimb flexing situation, protract, be designated as 0 fen as two forelimb symmetries; As the offside forelimb of performing the operation shoulder flexing, elbow flexing, shoulder inward turning occur or has concurrently, is designated as 1 fen.2. animal is placed on the plane, push away both shoulders respectively, check resistance to side shifting.As bilateral resistance equity and strong, be designated as 0 fen; As operation collateral resistance is descended, be designated as 1 fen.3. animal two forelimbs are put on the wire netting, observed muscular tension.Bilateral muscular tension equity and be 0 minute effectively; Operation offside muscle of anterior limb tension force descends and is designated as 1 fen.4. carry the Mus tail, animal has ceaselessly to operation offside revolver, is designated as 1 fen.According to above standard scoring, full marks are 4 minutes, and mark is high more, and the behavior disorder of animal is serious more.
4, the mensuration of cerebral infarction scope
Behind the animal via behavior scoring, broken end is got brain.The remainder that removes behind olfactory bulb, cerebellum and the low brain stem is cut into 5 crown below 4 ℃, and (every 5ml dye liquor contains 4%TTC 1.5ml rapidly the brain sheet to be placed the TTC dye liquor, 1M K2HP040.1ml, all the other adding distil waters are to scale), 37 ℃ of lucifuge temperature were incubated 30 minutes, took out to be placed on the 24h that keeps in Dark Place in 10% formalin.The non-ischemic region in dyed back is a rose, and infarct is a white.White organized carefully to dig down weigh, account for the percentage ratio of full brain weight and Ipsilateral brain weight as the cerebral infarction scope with blocking tissue's weight.
5, result
Above-mentioned experimental result represents with x ± s, and relatively t check between statistical test employing group the results are shown in Table 1 and table 2.
Several Chinese medicine extract of table 1 are to the influence of MCAO rat nervous symptoms (x ± s)
Dosage
Group number of animals nervous symptoms scoring in 6 hours nervous symptoms scoring in 24 hours
(mg/kg)
The Chinese medicine composition 6.7+13.3+2 10 1.78 ± 0.44 of embodiment one
* ##﹠amp;1.61 ± 0.63
* ##﹠amp;
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum)
The Chinese medicine composition 6.7+13.3+2 10 1.82 ± 0.41 of embodiment two
* ##﹠amp;1.77 ± 0.59
* ##﹠amp;
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Lignum Dalbergiae Odoriferae
Oil)
Radix Salviae Miltiorrhizae total phenolic acids+Radix Notoginseng total arasaponins 6.7+13.3 10 2.12 ± 0.60
* #2.04 ± 0.69
* #
Radix Salviae Miltiorrhizae total phenolic acids 20 10 2.96 ± 0.67 2.57 ± 0.42
*
Radix Notoginseng total arasaponins 20 10 2.68 ± 0.32
*2.51 ± 0.52
*
Annotate:
*P＜0.05 is compared with model group;
*P＜0.01 is compared with model group;
#P＜0.05 is compared with Radix Salviae Miltiorrhizae total phenolic acids or Radix Notoginseng total arasaponins group;
##P＜0.01 is compared with Radix Salviae Miltiorrhizae total phenolic acids or Radix Notoginseng total arasaponins group;
﹠amp;P＜0.05 is compared with Radix Salviae Miltiorrhizae total phenolic acids+Radix Notoginseng total arasaponins group
Several Chinese medicine extract of table 2 are to the influence of MCAO rat cerebral infarction scope (x ± s)
Dosage
Group number of animals infraction heavily accounts for full brain % infraction and heavily accounts for half brain %
(mg/kg)
The Chinese medicine composition 6.7+13.3+2 10 1.67 ± 0.70 of embodiment one
* ##﹠amp;3.37 ± 1.30
* ##﹠amp;
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum)
The Chinese medicine composition 6.7+13.3+2 10 1.58 ± 0.74 of embodiment two
* ##﹠amp;3.17 ± 1.41
* ##﹠amp;
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Lignum Dalbergiae Odoriferae
Oil)
Radix Salviae Miltiorrhizae total phenolic acids+Radix Notoginseng total arasaponins 6.7+13.3 10 2.34 ± 0.94
* #4.61 ± 1.80
* #
Radix Salviae Miltiorrhizae total phenolic acids 20 10 3.11 ± 0.86
*6.01 ± 1.66
*
Radix Notoginseng total arasaponins 20 10 3.08 ± 1.01
*5.99 ± 2.03
*
Annotate:
*P＜0.05 is compared with stalk type group;
*P＜0.01 is compared with model group;
#P＜0.05 is compared with Radix Salviae Miltiorrhizae total phenolic acids group or Radix Notoginseng total arasaponins group or XUESAITONG group;
##P＜0.01 is compared with Radix Salviae Miltiorrhizae total phenolic acids group or Radix Notoginseng total arasaponins group or XUESAITONG group;
﹠amp;P＜0.05 is compared with Radix Salviae Miltiorrhizae total phenolic acids+Radix Notoginseng total arasaponins group
The result of above table 1 and table 2 shows, each administration group all has tangible treating cerebral ischemia, the Chinese medicine composition of embodiment one (Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum) wherein, the curative effect of the Chinese medicine composition of embodiment two (Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Lignum Dalbergiae Odoriferae oil) is the strongest, single with Radix Salviae Miltiorrhizae total phenolic acids group or single similar to positive control drug XUESAITONG group curative effect with the Radix Notoginseng total arasaponins group, and Radix Salviae Miltiorrhizae total phenolic acids adds its curative effect of Radix Notoginseng total arasaponins group and is better than singly with Radix Salviae Miltiorrhizae total phenolic acids group or single with Radix Notoginseng total arasaponins group or XUESAITONG group, implements one Chinese medicine composition and the Chinese medicine composition of embodiment two but be weaker than.
The present invention adopts rat experiment myocardial infarction model and external perfusion method, has compared the function of resisting myocardial ischemia that Chinese medicine composition of the present invention, Radix Salviae Miltiorrhizae total phenolic acids add Radix Notoginseng total arasaponins, Radix Salviae Miltiorrhizae total phenolic acids, Radix Notoginseng total arasaponins.The result shows, Chinese medicine composition of the present invention has tangible function of resisting myocardial ischemia, its curative effect is better than using separately Radix Salviae Miltiorrhizae total phenolic acids or Radix Notoginseng total arasaponins, also be better than Radix Salviae Miltiorrhizae total phenolic acids and add Radix Notoginseng total arasaponins, show that Chinese medicine composition of the present invention is that Radix Salviae Miltiorrhizae extract adds Radix Notoginseng extract and adds Borneolum Syntheticum, perhaps Radix Salviae Miltiorrhizae extract adds Radix Notoginseng extract and adds the Lignum Dalbergiae Odoriferae oil three and have stronger synergism.
The experimentation of experimental example 2 several Chinese medicine extract function of resisting myocardial ischemia
1, grouping and administration
70 of Wister male rats, body weight 250.8 ± 24.6 is divided into 7 groups at random by body weight: the normal saline matched group; The XUESAITONG group; The Radix Salviae Miltiorrhizae total phenolic acids group; The Radix Notoginseng total arasaponins group; Radix Salviae Miltiorrhizae total phenolic acids adds the Radix Notoginseng total arasaponins group; Embodiment one Chinese medicine composition; Embodiment two Chinese medicine compositions.Each medicine all is diluted to desired concn with normal saline, and dosage is 4ml/kg, the tail intravenously administrable.
2, method
(1), rat experiment myocardial infarction model: animal pentobarbital sodium intraperitoneal injection of anesthesia (45mg/kg), it is fixing to face upward the position.Tracheal intubation is made the longitudinal incision of 2cm in breastbone left side, nearly breastbone side is cut off the 3rd, the 4th and reined in cartilage, open the thoracic cavity after, connect artificial respirator (ventilation 2ml/100g, 50 times/min).Cut off pericardium, expose heart, left anterior descending coronary artery root threading is in order to ligation, and record standard II lead electrocardiogram was stablized 10 minutes, and the ligation left anterior descending coronary artery is closed the thoracic cavity.With syringe sucking-off animal throat secretions, make animal recover autonomous respiration.Behind the ligation coronary artery 15min, intravenously administrable.Behind the ligation coronary artery 4 hours, win heart, 5 of the following crosscuts of ligature, carry out chlorination nitro blue tetrazolium (NBT) dyeing, calculating myocardium infarcted region area accounts for the percentage ratio of ventricle and heart area, and carries out statistical procedures (t check).
(2), stripped langendorff heart perfusion: carry out with reference to the pharmacological experimental methodology third edition.
3, result
(1), to the influence of rat experiment myocardial inyaretion scope, the results are shown in Table 3.
The various extracts of table 3 are to the influence of rat experiment myocardial inyaretion scope (x ± s)
Dosage
Group number of animals infarcted region/ventricle (%) infarcted region/heart (%)
(mg/kg)
The Chinese medicine composition 6+1,2+2 10 16.48 ± 6.14 of embodiment one
* ##﹠amp;12.85 ± 4.16
* ##﹠amp;
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum)
The Chinese medicine composition of embodiment two
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Lignum Dalbergiae Odoriferae 6+1,2+2 10 15.53 ± 4.57
* ##﹠amp;11.96 ± 3.25
* ##﹠amp;
Oil)
Radix Salviae Miltiorrhizae total phenolic acids+Radix Notoginseng total arasaponins 6.7+13.3 10 19.51 ± 7.58
* #14.83 ± 5.38
* #
Radix Salviae Miltiorrhizae total phenolic acids 20 10 23.98 ± 8.56 18.46 ± 4.89
*
Radix Notoginseng total arasaponins 20 10 26.84 ± 4.65
*20.93 ± 4.02
*
Annotate:
*P＜0.05 is compared with model group;
*P＜0.01 is compared with model group;
#P＜0.05 is compared with Radix Salviae Miltiorrhizae total phenolic acids or Radix Notoginseng total arasaponins group;
##P＜0.01 is compared with Radix Salviae Miltiorrhizae total phenolic acids or Radix Notoginseng total arasaponins group;
﹠amp;P＜0.05 is compared with Radix Salviae Miltiorrhizae total phenolic acids+Radix Notoginseng total arasaponins group
(2), to the influence of dirty coronary flow of guinea-pig heart and heart rate, the results are shown in Table 4.
The various extracts of table 4 are to the influence of dirty coronary flow of guinea-pig heart and heart rate (x ± s)
The coronary flow value added
Group dosage (mg/ml) heart rate attenuating value (inferior/min)
(ml/min)
The Chinese medicine composition 6+1,2+2 14.01 ± 1.86 of embodiment one
* ﹠amp;31 ± 12
* ﹠amp;
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum)
The Chinese medicine composition of embodiment two
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Lignum Dalbergiae Odoriferae 6+1,2+2 13.67 ± 1.74
* ﹠amp;32 ± 14
* ﹠amp;
Oil)
Radix Salviae Miltiorrhizae total phenolic acids+Radix Notoginseng total arasaponins 6.7+13.3 10.34 ± 2.04
*20 ± 9
*
Radix Salviae Miltiorrhizae total phenolic acids 20 7.11 ± 1.36 9 ± 5
Radix Notoginseng total arasaponins 20 8.08 ± 1.01 10 ± 4
Annotate:
*P＜0.05 is compared with Radix Salviae Miltiorrhizae total phenolic acids group or Radix Notoginseng total arasaponins group or XUESAITONG group;
*P＜0.01 is compared with Radix Salviae Miltiorrhizae total phenolic acids group or Radix Notoginseng total arasaponins group or XUESAITONG group;
﹠amp;P＜0.05 is compared with Radix Salviae Miltiorrhizae total phenolic acids+Radix Notoginseng total arasaponins group
The result of above table 3 and table 4 shows, each administration group all has tangible function of resisting myocardial ischemia, the Chinese medicine composition of embodiment one (Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum) wherein, the curative effect of the Chinese medicine composition of embodiment two (Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Lignum Dalbergiae Odoriferae oil) is the strongest, single with Radix Salviae Miltiorrhizae total phenolic acids group or single similar to positive control drug XUESAITONG group curative effect with the Radix Notoginseng total arasaponins group, and Radix Salviae Miltiorrhizae total phenolic acids+its curative effect of Radix Notoginseng total arasaponins group is better than list with the Radix Salviae Miltiorrhizae total phenolic acids group or singly with Radix Notoginseng total arasaponins group or XUESAITONG group, but is weaker than the Chinese medicine composition of enforcement one and the Chinese medicine composition of embodiment two.
Experimental example 3
Experiment material and experimental technique are with experimental example 1, and wherein being subjected to reagent is the Chinese medicine composition of embodiment one, embodiment three, embodiment four, embodiment five, embodiment six.
Above-mentioned experimental result represents with x ± s, and relatively t check between statistical test employing group the results are shown in Table 5 and table 6.
Different Radix Salviae Miltiorrhizae total phenolic acids+Radix Notoginseng total arasaponins+the Borneolum Syntheticums formed of table 5 are to the influence of (MCAO) rat nervous symptoms (x ± s)
Dosage
Group number of animals nervous symptoms scoring in 6 hours nervous symptoms scoring in 24 hours
(mg/kg)
The Chinese medicine composition of embodiment three (2.2+17.8)
10???????1.98±0.44
**???????1.82±0.63
**
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum)+2
The Chinese medicine composition of embodiment four (4+16)
10???????2.19±0.65
**???????1.98±0.52
**
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum)+2
Chinese medicine composition (the 13.3+6.7 of embodiment one
10???????1.92±0.42
**???????1.78±0.34
**
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum))+2
The Chinese medicine composition of embodiment five (10+10)
10???????2.08±0.60
**???????1.80±0.72
**
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum)+2
Embodiment six Chinese medicine composition (13.3+6.7
10???????1.92±0.42
**???????1.78±0.34
**
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum))+2
Annotate:
*Significant difference has been compared with model group in P＜0.01; Compare unknown significance difference between each administration group.
Different Radix Salviae Miltiorrhizae total phenolic acids+Radix Notoginseng total arasaponins+the Borneolum Syntheticums formed of table 6 are to the influence of (MCAO) rat cerebral infarction scope
( x±s)
Dosage
Group number of animals infraction heavily accounts for full brain % infraction and heavily accounts for half brain %
(mg/kg)
The Chinese medicine composition 2.2+17.8+2 10 2.02 ± 0.95 of embodiment three
*4.03 ± 1.86
*
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum)
The Chinese medicine composition 4+1,6+2 10 1.83 ± 0.94 of embodiment four
*3.68 ± 1.81
*
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum)
The Chinese medicine composition 6.7+13.3+2 10 1.77 ± 0.70 of embodiment one
*3.57 ± 1.36
*
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum)
The Chinese medicine composition 1,0+1,0+2 10 1.98 ± 1.01 of embodiment five
*4.09 ± 2.03
*
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum)
Embodiment six Chinese medicine composition 13.3+6.7+2 10 2.12 ± 0.86
*4.28 ± 1.69
*
(Radix Salviae Miltiorrhizae extract+Radix Notoginseng extract+Borneolum Syntheticum)
Annotate:
*Significant difference has been compared with model group in P＜0.01; Compare unknown significance difference between each administration group
Above result shows, compare with model group, the nervous symptoms of each administration group rat obviously improves (seeing Table 5), the cerebral infarction scope is all obviously dwindled (seeing Table 6), show that variant ratio compatibility group all has tangible treating cerebral ischemia, and the curative effect with the Chinese medicine composition of embodiment one among the result is more excellent relatively, but does not see obvious significant difference between each administration group group.
Description of drawings
Fig. 1: Radix Salviae Miltiorrhizae extract HPLC finger printing (0～60 minute)
Fig. 2: Radix Notoginseng extract HPLC finger printing (0～30 minute)
The specific embodiment
To be easier to understand the present invention with reference to the following example, and provide embodiment and be in order to illustrate the present invention, rather than in order to limit the scope of the invention.
Embodiment one
Radix Salviae Miltiorrhizae extract: the preparation method by Chinese patent application (application number 02117923.9) obtains.Concrete extracting method is: Radix Salviae Miltiorrhizae 5kg is ground into coarse powder, adds deionized water heating extraction 3 times under 100 ℃ of slight boiling conditions.5.5 times of water heated 1 hour for the first time; Second and third time respectively adds 3 times of water gagings and heated respectively 0.5 hour.Extracting solution filters after transferring pH value to be 2 with 10% hydrochloric acid, polyamide column on the filtrate (dried resin amount make a living dose 2/3).With the washing of 5 times of amount deionizations, continue with 0.1% sodium bicarbonate aqueous solution eluting, consumption is 5 times of column volume.Collect eluent, transfer PH to 2 back to go up D with 10% hydrochloric acid
101Macroporous adsorbent resin, continues to use 95% ethanol elution to neutral with deionized water rinsing, treats that colour band gets off promptly to collect this colour band.Concentrating under reduced pressure is collected liquid to doing to the greatest extent, spend the night with suitable quantity of water dissolving back refrigerator cold-storage, promptly get the Radix Salviae Miltiorrhizae total phenolic acids extracting solution by 0.3 μ m cellulose mixture filtering with microporous membrane, with lyophilization immediately behind the 2% sodium hydroxide adjusting pH value to 6.0, Radix Salviae Miltiorrhizae extract raw material lyophilized powder 221g, product yield 4.4% of the dose of making a living.
Salvianolic acid B is 53.73% in the above-mentioned Radix Salviae Miltiorrhizae extract, and salvianolic acid E is 3.7%, and rosmarinic acid is 5.2%, and alkannic acid is 1.7%, and its Radix Salviae Miltiorrhizae total phenolic acids content is 83.94%.Above-mentioned Radix Salviae Miltiorrhizae extract HPLC finger printing (10 batches) has 6 total peaks.The average relative retention time at 6 total peaks is followed successively by 0.60 (salvianolic acid E peak), 0.68 (rosmarinic acid peak), 0.73 (alkannic acid peak), 1 (salvianolic acid B), 1.08,1.26.In the total peak unimodal area account for total peak area greater than 20% have only salvianolic acid B (promptly with reference to the peak), the peak area at salvianolic acid B peak (promptly with reference to the peak) accounts for 72% (on average) of total peak area, its relative peak area is 1; The peak area at rosmarinic acid peak accounts for 10% (on average) of total peak area, and its relative peak area is 0.14 (on average).The non-total peak gross area is not more than 10% of total peak area.Above-mentioned Radix Salviae Miltiorrhizae extract HPLC finger printing is seen Fig. 1.
Buy Radix Notoginseng total arasaponins from market, further refining through routine, get Radix Notoginseng extract.The ginsenoside Re is 3.9% in the Radix Notoginseng extract, and the ginsenoside Rg1 is 34.3%, and the ginsenoside Rb1 is 31.0%, and the ginsenoside Rd is 8.8%, and arasaponin R1 is 6.8%, and its content of the total saponins in radix notoginseng is 94%.Radix Notoginseng extract HPLC finger printing (10 batches average) has 11 total peaks.The average relative retention time at 11 total peaks is followed successively by 0.82 (arasaponin R1 peak), 0.94 (ginsenoside Re peak), 1 (the ginsenoside Rg1 peak is promptly with reference to the peak), 2.63,2.74,2.79,2.85 (ginsenoside Rb1 peaks), 2.99,3.08,3.18 (ginsenoside Rd peaks), 3.28.In the total peak unimodal area account for total peak area greater than 20% ginsenoside Rg1 peak and ginsenoside Rb1 peak arranged.The peak area at ginsenoside Rg1 peak (promptly with reference to the peak) accounts for 28% (on average) of total peak area, and its relative peak area is 1; The peak area at ginsenoside Rb1 peak accounts for 39% (on average) of total peak area, and its relative peak area is 1.36 (on average); The peak area at arasaponin R1 peak accounts for 6% (on average) of total peak area, and its relative peak area is 0.20 (on average); The peak area at ginsenoside Rd peak accounts for 10% (on average) of total peak area, and its relative peak area is 0.37 (on average).The non-total peak gross area is not more than 10% of total peak area.Radix Notoginseng extract HPLC finger printing is seen Fig. 2.
Get above-mentioned Radix Salviae Miltiorrhizae extract 100mg, above-mentioned Radix Notoginseng extract 200mg, Borneolum Syntheticum 30mg, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment two
Get Radix Notoginseng extract 200mg, the Lignum Dalbergiae Odoriferae oil 30mg of Radix Salviae Miltiorrhizae extract 100mg, the embodiment one of embodiment one, add 400mg Polyethylene Glycol-6000 mix homogeneously, fusion gets Chinese medicine composition after the cooling.
Embodiment three
Get Radix Notoginseng extract 267mg, the Borneolum Syntheticum 30mg of Radix Salviae Miltiorrhizae extract 33mg, the embodiment one of embodiment one, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment four
Get Radix Notoginseng extract 240mg, the Borneolum Syntheticum 30mg of Radix Salviae Miltiorrhizae extract 60mg, the embodiment one of embodiment one, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment five
Get Radix Notoginseng extract 150mg, the Borneolum Syntheticum 30mg of Radix Salviae Miltiorrhizae extract 150mg, the embodiment one of embodiment one, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment six
Get Radix Notoginseng extract 100mg, the Borneolum Syntheticum 30mg of Radix Salviae Miltiorrhizae extract 200mg, the embodiment one of embodiment one, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment seven
Get Radix Notoginseng extract 214mg, the Borneolum Syntheticum 31mg of Radix Salviae Miltiorrhizae extract 85mg, the embodiment one of embodiment one, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment eight
Get Radix Notoginseng extract 96mg, the Camphora 10mg of Radix Salviae Miltiorrhizae extract 224mg, the embodiment one of embodiment one, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment nine
Get Radix Notoginseng extract 293mg, the Borneolum Syntheticum 20mg of Radix Salviae Miltiorrhizae extract 17mg, the embodiment one of embodiment one, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment ten
Get Radix Notoginseng extract 165mg, the Borneolum Syntheticum 48mg of Radix Salviae Miltiorrhizae extract 117mg, the embodiment one of embodiment one, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment 11
Get Radix Notoginseng extract 214mg, the Lignum Dalbergiae Odoriferae oil 31mg of Radix Salviae Miltiorrhizae extract 85mg, the embodiment one of embodiment one, add 400mg Polyethylene Glycol-6000 mix homogeneously, fusion gets Chinese medicine composition after the cooling.
Embodiment 12
Get Radix Notoginseng extract 96mg, the Lignum Dalbergiae Odoriferae oil 10mg of Radix Salviae Miltiorrhizae extract 224mg, the embodiment one of embodiment one, add 400mg Polyethylene Glycol-6000 mix homogeneously, fusion gets Chinese medicine composition after the cooling.
Embodiment 13
Get Radix Notoginseng extract 293mg, the Lignum Dalbergiae Odoriferae oil 20mg of Radix Salviae Miltiorrhizae extract 17mg, the embodiment one of embodiment one, add 400mg Polyethylene Glycol-6000 mix homogeneously, fusion gets Chinese medicine composition after the cooling.
Embodiment 14
Get Radix Notoginseng extract 165mg, the Lignum Dalbergiae Odoriferae oil 48mg of Radix Salviae Miltiorrhizae extract 117mg, the embodiment one of embodiment one, add 400mg Polyethylene Glycol-6000 mix homogeneously, fusion gets Chinese medicine composition after the cooling.
Get Radix Notoginseng extract 135g, Borneolum Syntheticum 30g, mannitol 90g, calcium disodium edetate 15g and the distilled water 15ml of Radix Salviae Miltiorrhizae extract 165g, the embodiment one of embodiment one, behind the said components mixing, lyophilization, 1000 of packing.
Embodiment 16
Get Radix Notoginseng extract 180g, the Borneolum Syntheticum 14g of Radix Salviae Miltiorrhizae extract 136g (Chinese patent CN1352985A embodiment 1), embodiment one, with 40g microcrystalline Cellulose mix homogeneously, add 3% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules, 60 ℃ of dryings 30～45 minutes, granulate, add the 4g Pulvis Talci, mixing fills in capsule, promptly.
Embodiment 17
(water is proposed the preparation of 75% alcohol deposition method: Guo Ying etc., Yunnan University of Traditional Chinese Medicine's journal, 2001 to get Radix Salviae Miltiorrhizae extract 33g, 6), Radix Notoginseng extract 290g (Qian Tianxiang etc., foreign medical science plant amedica fascicle, 1,997 24 (4):, 12 (4)), Borneolum Syntheticum 7g, use a small amount of physiological saline solution respectively, it is an amount of to add tween～80, grind evenly, add the normal saline rear decoloring again, sucking filtration is clear and bright to solution, is loaded in the saline bottle, sealing, the boiling water heat sterilization; Three kinds of clear and bright liquid are mixed again, transfer pH to 5, add normal saline to an amount of, sucking filtration promptly gets injection to clear and bright.
Embodiment 18
Get Radix Salviae Miltiorrhizae extract 120g (Chinese patent CN1384090A embodiment 1), Radix Notoginseng extract 170g (Tang's light, Chinese patent medicine, 1990,5), Borneolum Syntheticum 38g 12 (8):,, add 3% polyvidone alcoholic solution system soft material with 40g microcrystalline Cellulose mix homogeneously, cross 18 mesh sieve system granules, 60 ℃ of dryings 30～45 minutes, granulate adds the 4g Pulvis Talci, mixing, mixing, tabletting, promptly.
Embodiment 19
Get Radix Notoginseng extract 50g, the Borneolum Syntheticum 17g of Radix Salviae Miltiorrhizae extract 263g (Chinese patent CN1384090A embodiment 1), embodiment one, with 40g microcrystalline Cellulose mix homogeneously, add 3% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules, 60 ℃ of dryings 30～45 minutes, granulate, add the 4g Pulvis Talci, mixing, granulate, pack, promptly.
Get Radix Salviae Miltiorrhizae extract 18g (Chinese patent CN1384090A embodiment 1), embodiment one Radix Notoginseng extract 305g, Borneolum Syntheticum 7g, with 700g Polyethylene Glycol-6000 mix homogeneously, fusion splashes in the cryogenic liquid paraffin, selects ball, removes liquid paraffin, promptly.
Embodiment 21
Get Radix Notoginseng extract 180g, the Lignum Dalbergiae Odoriferae oil 14g of Radix Salviae Miltiorrhizae extract 136g (Chinese patent CN1352985A embodiment 1), embodiment one, with 40g microcrystalline Cellulose mix homogeneously, add 3% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules, 60 ℃ of dryings 30～45 minutes, granulate, add the 4g Pulvis Talci, mixing fills in capsule, promptly.
Embodiment 22
Get Radix Salviae Miltiorrhizae extract 120g (Chinese patent CN1384090A embodiment 1), Radix Notoginseng extract 170g (Tang's light, Chinese patent medicine, 1990,5), Borneolum Syntheticum 38g 12 (8):,, add 3% polyvidone alcoholic solution system soft material with 40g microcrystalline Cellulose mix homogeneously, cross 18 mesh sieve system granules, 60 ℃ of dryings 30～45 minutes, granulate adds the 4g Pulvis Talci, mixing, mixing, tabletting, promptly.
Embodiment 23
Get Radix Notoginseng extract 50g, the Borneolum Syntheticum 17g of Radix Salviae Miltiorrhizae extract 263g (Chinese patent CN1384090A embodiment 1), embodiment one, with 40g microcrystalline Cellulose mix homogeneously, add 3% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules, 60 ℃ of dryings 30～45 minutes, granulate, add the 4g Pulvis Talci, mixing, granulate, pack, promptly.
Embodiment 24
Get Radix Notoginseng extract 305g, the Borneolum Syntheticum 7g of Radix Salviae Miltiorrhizae extract 18g (Chinese patent CN1384090A embodiment 1), embodiment one, with 700g Polyethylene Glycol-6000 mix homogeneously, fusion splashes in the cryogenic liquid paraffin, selects ball, removes liquid paraffin, promptly.
Claims (14)
1. Chinese medicine composition for the treatment of cardiovascular and cerebrovascular disease, form by following component by weight percentage:
Radix Salviae Miltiorrhizae extract 5.0%～80.0%
Radix Notoginseng extract 15.0%～93.0%
Borneolum Syntheticum or Camphora 2.0%～15.0%
Content of danshinolic acid B is 45%～70% in the above-mentioned Radix Salviae Miltiorrhizae extract, and salvianolic acid E content is 2～10%, and rosmarinic acid contents is 4%～20%, and alkannic acid content is 1%～10%, and its total phenolic content is more than 70%; Arasaponin R1 content is 2%～10% in the Radix Notoginseng extract, ginsenoside Re's content is 2%～6%, and ginsenoside Rg1's content is 15%～40%, and ginsenoside Rb1's content is 15%～40%, ginsenoside Rd's content is 5%～12%, and the content of its Radix Notoginseng total arasaponins is more than 70%.
2. the described Chinese medicine composition of claim 1 is characterized in that, the percentage by weight of described each component is:
Radix Salviae Miltiorrhizae extract 10.0%～68.0%
Radix Notoginseng extract 30.0%～88.0%
Borneolum Syntheticum or Camphora 2.0%～12.0%
Content of danshinolic acid B is 45%～70% in the above-mentioned Radix Salviae Miltiorrhizae extract, and salvianolic acid E content is 2～10%, and rosmarinic acid contents is 4%～20%, and alkannic acid content is 1%～10%, and its total phenolic content is more than 70%; Arasaponin R1 content is 2%～10% in the Radix Notoginseng extract, ginsenoside Re's content is 2%～6%, and ginsenoside Rg1's content is 15%～40%, and ginsenoside Rb1's content is 15%～40%, ginsenoside Rd's content is 5%～12%, and the content of its Radix Notoginseng total arasaponins is more than 70%.
3. the described Chinese medicine composition of claim 1 is characterized in that, the percentage by weight of described each component is:
Radix Salviae Miltiorrhizae extract 25.0%～50.0%
Radix Notoginseng extract 40.0%～65.0%
Borneolum Syntheticum or Camphora 4.0%～10.0%
Content of danshinolic acid B is 45%～70% in the above-mentioned Radix Salviae Miltiorrhizae extract, and salvianolic acid E content is 2～10%, and rosmarinic acid contents is 4%～20%, and alkannic acid content is 1%～10%, and its total phenolic content is more than 70%; Arasaponin R1 content is 2%～10% in the Radix Notoginseng extract, ginsenoside Re's content is 2%～6%, and ginsenoside Rg1's content is 15%～40%, and ginsenoside Rb1's content is 15%～40%, ginsenoside Rd's content is 5%～12%, and the content of its Radix Notoginseng total arasaponins is more than 70%.
4. the described Chinese medicine composition of claim 1 is characterized in that, the percentage by weight of described each component is:
Radix Salviae Miltiorrhizae extract 30.3%
Radix Notoginseng extract 60.6%
Borneolum Syntheticum or Camphora 9.1%
Content of danshinolic acid B is 45%～70% in the above-mentioned Radix Salviae Miltiorrhizae extract, and salvianolic acid E content is 2～10%, and rosmarinic acid contents is 4%～20%, and alkannic acid content is 1%～10%, and its total phenolic content is more than 70%; Arasaponin R1 content is 2%～10% in the Radix Notoginseng extract, ginsenoside Re's content is 2%～6%, and ginsenoside Rg1's content is 15%～40%, and ginsenoside Rb1's content is 15%～40%, ginsenoside Rd's content is 5%～12%, and the content of its Radix Notoginseng total arasaponins is more than 70%.
5. the arbitrary described Chinese medicine composition of claim 1～4 is characterized in that,
The HPLC finger printing of described Radix Salviae Miltiorrhizae extract has 5～7 total peaks, in the total peak unimodal area account for total peak area greater than 20% have only the salvianolic acid B peak, the salvianolic acid B peak promptly accounts for total peak area 57%～87% with reference to the peak area at peak, its relative peak area is 1; The peak area at rosmarinic acid peak accounts for total peak area 3%～18% in the total peak, and its relative peak area is 0.03～0.25; The non-total peak gross area is not more than 10% of total peak area;
The finger printing of described Radix Notoginseng extract has 9～12 total peaks, in the total peak unimodal area account for total peak area greater than 20% ginsenoside Rg1 peak and ginsenoside Rb1 peak arranged, the ginsenoside Rg1 peak promptly accounts for total peak area 20%～35% with reference to the peak area at peak in the total peak, and its relative peak area is 1; The peak area at ginsenoside Rb1 peak accounts for total peak area 30%～50% in the total peak, and its relative peak area is 0.85～2.50; The peak area at arasaponin R1 peak accounts for total peak area 2%～8% in the total peak, and its relative peak area is 0.06～0.40; The peak area at ginsenoside Rd peak accounts for total peak area 5%～14% in the total peak, and its relative peak area is 0.14～0.70.The non-total peak gross area is not more than 10% of total peak area.
6. the arbitrary described Chinese medicine composition of claim 1～4 is characterized in that,
The HPLC finger printing of described Radix Salviae Miltiorrhizae extract has 6 total peaks, the relative retention time at 6 total peaks is followed successively by 0.55～0.65 (salvianolic acid E peak), 0.66～0.70 (rosmarinic acid peak), 0.71～0.79 (alkannic acid peak), 1 (the salvianolic acid B peak is promptly with reference to the peak), 1.03～1.12,1.21～1.30.
The HPLC finger printing of described Radix Notoginseng extract has 11 total peaks, the relative retention time at 11 total peaks is followed successively by 0.77～0.85 (arasaponin R1 peak), 0.87～0.97 (ginsenoside Re peak), 1 (the ginsenoside Rg1 peak is promptly with reference to the peak), 2.58～2.67,0.68～2.76,2.77～2.81,2.82～2.91 (ginsenoside Rb1 peaks), 2.95～3.03,3.05～3.13,3.15～3.22 (ginsenoside Rd peaks), 3.24～3.91.
7. the arbitrary described Chinese medicine composition of claim 1～4 is characterized in that, Radix Salviae Miltiorrhizae total phenolic acids content is more than 80% in the described Radix Salviae Miltiorrhizae extract, and content of the total saponins in radix notoginseng is more than 80% in the described Radix Notoginseng extract.
8. the arbitrary described Chinese medicine composition of claim 1～4 is injection, tablet, drop pill, granule, injectable powder, capsule, the microgranule that active component is made.
9. the described Chinese medicine composition of claim 8 is injection, the injectable powder that active component is made.
10. the arbitrary described Chinese medicine composition of claim 1～4 is characterized in that, replaces Borneolum Syntheticum or Camphora with Lignum Dalbergiae Odoriferae oil.
11. the described Chinese medicine composition of claim 5 is characterized in that, replaces Borneolum Syntheticum or Camphora with Lignum Dalbergiae Odoriferae oil.
12. the described Chinese medicine composition of claim 6 is characterized in that, replaces Borneolum Syntheticum or Camphora with Lignum Dalbergiae Odoriferae oil.
13. the described Chinese medicine composition of claim 10 is characterized in that, Radix Salviae Miltiorrhizae total phenolic acids content is more than 80% in the described Radix Salviae Miltiorrhizae extract, and content of the total saponins in radix notoginseng is more than 80% in the described Radix Notoginseng extract.
Injection, tablet, drop pill, granule, injectable powder, capsule, microgranule that 14. the described Chinese medicine composition of claim 10 is an active component to be made.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031443109A CN100404035C (en) | 2003-09-23 | 2003-09-23 | Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031443109A CN100404035C (en) | 2003-09-23 | 2003-09-23 | Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1600318A true CN1600318A (en) | 2005-03-30 |
| CN100404035C CN100404035C (en) | 2008-07-23 |
Family
ID=34659483
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031443109A Expired - Lifetime CN100404035C (en) | 2003-09-23 | 2003-09-23 | Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100404035C (en) |
Cited By (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100400047C (en) * | 2006-04-05 | 2008-07-09 | 黑龙江省珍宝岛制药有限公司 | Medicine powder for injection for treating cardiac and cerebral vascular diseases and its preparing method and application |
| CN100563662C (en) * | 2006-11-28 | 2009-12-02 | 中国科学院上海药物研究所 | Chinese medicine active ingredient composition of treatment cardiovascular disease and preparation method thereof |
| CN1919239B (en) * | 2005-08-24 | 2010-09-29 | 天津天士力制药股份有限公司 | Traditional medicine composition for treating cardiovascular and cerebrovascular diseases |
| CN1919240B (en) * | 2005-08-24 | 2011-02-16 | 天津天士力制药股份有限公司 | Traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases |
| CN1919247B (en) * | 2005-08-24 | 2011-02-16 | 天津天士力制药股份有限公司 | Chinese medicine for treating cardiovascular and cerebrovascular disease |
| CN1919243B (en) * | 2005-08-24 | 2011-03-23 | 天津天士力制药股份有限公司 | Traditional medicine composition for treating cardiovascular and cerebrovascular diseases |
| CN102028748A (en) * | 2009-09-29 | 2011-04-27 | 天津天士力现代中药资源有限公司 | Drug for treating coronary heart disease and extraction process |
| CN1919248B (en) * | 2005-08-24 | 2011-04-27 | 天津天士力制药股份有限公司 | Traditional Chinese medicinal formulation for treating cardiovascular and cerebrovascular disease |
| CN1919245B (en) * | 2005-08-24 | 2011-07-13 | 天津天士力制药股份有限公司 | Traditional medicine composition for treating cardiovascular and cerebrovascular diseases |
| CN1919250B (en) * | 2005-08-24 | 2011-08-10 | 天津天士力制药股份有限公司 | Traditional Chinese medicinal formulation for treating cardiovascular and cerebrovascular disease |
| CN101708240B (en) * | 2009-12-08 | 2011-08-17 | 山西医科大学 | Heard-brain benefiting dropping pills and method for preparing same |
| CN101085000B (en) * | 2006-06-08 | 2012-04-18 | 天津天士力之骄药业有限公司 | Compound red sage root freezing-dried powder injection containing salvianolic acid B and its preparation method |
| CN103006838A (en) * | 2013-01-05 | 2013-04-03 | 山东沃华医药科技股份有限公司 | Traditional Chinese medicine composition for treating cardiovascular and cerebrovascular diseases |
| CN102028739B (en) * | 2009-09-29 | 2014-01-29 | 天津天士力现代中药资源有限公司 | Drug for treating coronary heart disease and preparation method thereof |
| CN104224811A (en) * | 2013-06-17 | 2014-12-24 | 天士力制药集团股份有限公司 | Salvia miltiorrhiza medicine and preparation method thereof |
| WO2015003662A1 (en) * | 2013-07-11 | 2015-01-15 | 天士力制药集团股份有限公司 | Traditional chinese medicine composition, and preparation and application thereof |
| JP2016534119A (en) * | 2013-08-29 | 2016-11-04 | タスリー・ファーマシューティカル・グループ・カンパニー・リミテッドＴａｓｌｙ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｇｒｏｕｐ Ｃｏ．， Ｌｔｄ． | Novel salvianolic acid compound T, its preparation method and use |
| EP3020408A4 (en) * | 2013-07-11 | 2017-03-15 | Tasly Pharmaceutical Group Co., Ltd. | Traditional chinese medicine composition, and preparation and application thereof |
| CN108096318A (en) * | 2017-12-29 | 2018-06-01 | 北京中医药大学 | Treat pharmaceutical composition of cardiovascular and cerebrovascular disease and its preparation method and application |
| CN108484547A (en) * | 2013-10-17 | 2018-09-04 | 兰赫(上海)生物科技有限公司 | A kind of alkannic acid of high-purity and its preparation method and application |
| CN110339232A (en) * | 2018-04-04 | 2019-10-18 | 天士力医药集团股份有限公司 | A kind of Chinese medicine composition prevented and/or treat ischemical reperfusion injury |
| US11013694B2 (en) | 2013-07-11 | 2021-05-25 | Tasly Pharmaceutical Group Co., Ltd. | Formulation of a micro drop pill and the preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1349818A (en) * | 2001-10-24 | 2002-05-22 | 沈阳药科大学 | Effective part group in red sage mixture and its delayed release prepn. medicinal use and prepn process |
| CN1296063C (en) * | 2002-12-23 | 2007-01-24 | 北京采瑞医药有限公司 | Compound red sage prepn for treating cardiac and cerebral vascular diseases and its prepn process |
-
2003
- 2003-09-23 CN CNB031443109A patent/CN100404035C/en not_active Expired - Lifetime
Cited By (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1919245B (en) * | 2005-08-24 | 2011-07-13 | 天津天士力制药股份有限公司 | Traditional medicine composition for treating cardiovascular and cerebrovascular diseases |
| CN1919247B (en) * | 2005-08-24 | 2011-02-16 | 天津天士力制药股份有限公司 | Chinese medicine for treating cardiovascular and cerebrovascular disease |
| CN1919248B (en) * | 2005-08-24 | 2011-04-27 | 天津天士力制药股份有限公司 | Traditional Chinese medicinal formulation for treating cardiovascular and cerebrovascular disease |
| CN1919240B (en) * | 2005-08-24 | 2011-02-16 | 天津天士力制药股份有限公司 | Traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases |
| CN1919250B (en) * | 2005-08-24 | 2011-08-10 | 天津天士力制药股份有限公司 | Traditional Chinese medicinal formulation for treating cardiovascular and cerebrovascular disease |
| CN1919243B (en) * | 2005-08-24 | 2011-03-23 | 天津天士力制药股份有限公司 | Traditional medicine composition for treating cardiovascular and cerebrovascular diseases |
| CN1919239B (en) * | 2005-08-24 | 2010-09-29 | 天津天士力制药股份有限公司 | Traditional medicine composition for treating cardiovascular and cerebrovascular diseases |
| CN100400047C (en) * | 2006-04-05 | 2008-07-09 | 黑龙江省珍宝岛制药有限公司 | Medicine powder for injection for treating cardiac and cerebral vascular diseases and its preparing method and application |
| CN101085000B (en) * | 2006-06-08 | 2012-04-18 | 天津天士力之骄药业有限公司 | Compound red sage root freezing-dried powder injection containing salvianolic acid B and its preparation method |
| CN100563662C (en) * | 2006-11-28 | 2009-12-02 | 中国科学院上海药物研究所 | Chinese medicine active ingredient composition of treatment cardiovascular disease and preparation method thereof |
| CN102028748A (en) * | 2009-09-29 | 2011-04-27 | 天津天士力现代中药资源有限公司 | Drug for treating coronary heart disease and extraction process |
| CN102028739B (en) * | 2009-09-29 | 2014-01-29 | 天津天士力现代中药资源有限公司 | Drug for treating coronary heart disease and preparation method thereof |
| CN101708240B (en) * | 2009-12-08 | 2011-08-17 | 山西医科大学 | Heard-brain benefiting dropping pills and method for preparing same |
| CN103006838A (en) * | 2013-01-05 | 2013-04-03 | 山东沃华医药科技股份有限公司 | Traditional Chinese medicine composition for treating cardiovascular and cerebrovascular diseases |
| CN103006838B (en) * | 2013-01-05 | 2014-06-11 | 山东沃华医药科技股份有限公司 | Traditional Chinese medicine composition for treating cardiovascular and cerebrovascular diseases |
| CN104224811B (en) * | 2013-06-17 | 2019-02-05 | 天士力医药集团股份有限公司 | A kind of Radix Salviae Miltiorrhizae drug and preparation method thereof |
| CN104224811A (en) * | 2013-06-17 | 2014-12-24 | 天士力制药集团股份有限公司 | Salvia miltiorrhiza medicine and preparation method thereof |
| WO2015003662A1 (en) * | 2013-07-11 | 2015-01-15 | 天士力制药集团股份有限公司 | Traditional chinese medicine composition, and preparation and application thereof |
| EP3020407A1 (en) * | 2013-07-11 | 2016-05-18 | Tasly Pharmaceutical Group Co., Ltd. | Traditional chinese medicine composition, and preparation and application thereof |
| EP3020408A4 (en) * | 2013-07-11 | 2017-03-15 | Tasly Pharmaceutical Group Co., Ltd. | Traditional chinese medicine composition, and preparation and application thereof |
| EP3020407A4 (en) * | 2013-07-11 | 2017-05-03 | Tasly Pharmaceutical Group Co., Ltd. | Traditional chinese medicine composition, and preparation and application thereof |
| USRE49050E1 (en) | 2013-07-11 | 2022-04-26 | Tasly Pharmaceutical Group Co., Ltd. | Traditional Chinese medicine composition, and preparation and application thereof |
| US9987320B2 (en) | 2013-07-11 | 2018-06-05 | Tasly Pharmaceutical Group Co., Ltd. | Traditional chinese medicine composition, and preparation and application thereof |
| US9999630B2 (en) | 2013-07-11 | 2018-06-19 | Tasly Pharmaceutical Group Co., Ltd. | Traditional chinese medicine composition, and preparation and application thereof |
| TWI631956B (en) * | 2013-07-11 | 2018-08-11 | 大陸商天士力醫藥集團股份有限公司 | Traditional Chinese medicine composition and use thereof, medicinal preparation containing the traditional Chinese medicine composition and compound salvia miltiorrhiza micropill, and preparation method of the microdrop pill |
| USRE49035E1 (en) | 2013-07-11 | 2022-04-19 | Tasly Pharmaceutical Group Co., Ltd. | Traditional Chinese medicine composition, and preparation and application thereof |
| US11013694B2 (en) | 2013-07-11 | 2021-05-25 | Tasly Pharmaceutical Group Co., Ltd. | Formulation of a micro drop pill and the preparation method thereof |
| AU2014289763B2 (en) * | 2013-07-11 | 2019-03-07 | Tasly Pharmaceutical Group Co., Ltd. | Traditional chinese medicine composition, and preparation and application thereof |
| AU2014289766B2 (en) * | 2013-07-11 | 2019-03-14 | Tasly Pharmaceutical Group Co., Ltd. | Traditional chinese medicine composition, and preparation and application thereof |
| US10626077B2 (en) | 2013-08-29 | 2020-04-21 | Tasly Pharmaceutical Group Co., Ltd. | Salvianolic acid compound T, preparation method therefor, and use thereof |
| JP2016534119A (en) * | 2013-08-29 | 2016-11-04 | タスリー・ファーマシューティカル・グループ・カンパニー・リミテッドＴａｓｌｙ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｇｒｏｕｐ Ｃｏ．， Ｌｔｄ． | Novel salvianolic acid compound T, its preparation method and use |
| CN108484547A (en) * | 2013-10-17 | 2018-09-04 | 兰赫(上海)生物科技有限公司 | A kind of alkannic acid of high-purity and its preparation method and application |
| CN108096318A (en) * | 2017-12-29 | 2018-06-01 | 北京中医药大学 | Treat pharmaceutical composition of cardiovascular and cerebrovascular disease and its preparation method and application |
| CN110339232A (en) * | 2018-04-04 | 2019-10-18 | 天士力医药集团股份有限公司 | A kind of Chinese medicine composition prevented and/or treat ischemical reperfusion injury |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100404035C (en) | 2008-07-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100339085C (en) | Combination of Chinese traditional medicine for curing cardiovascular and cerebrovascular diseases | |
| CN1600318A (en) | Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease | |
| CN1457829A (en) | Chinese medicine composition for curing chronic atrophic sastritis and its preparing method and quality control method | |
| CN1425448A (en) | Medicine for curing thrombotic phlebitis | |
| CN1919248A (en) | Traditional Chinese medicinal formulation for treating cardiovascular and cerebrovascular disease | |
| CN101032503A (en) | Effective elements of Chinese traditional medicine combination for curing cardiovascular disease and the quality control method | |
| CN1698878A (en) | Kidney replenishing medicinal composition and its preparation process and novel use | |
| CN1283291C (en) | Compound preparation for bone fracture and its preparation method | |
| CN1872199A (en) | Composition of Chinese traditional medicine, and preparation method | |
| CN1919240A (en) | Traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases | |
| CN1903238A (en) | Extractive of traditional Chinese medicine, its prepns., preparing method and application thereof | |
| CN1820770A (en) | Chinese medicine composition for treating apoplexy and its preparing method | |
| CN1919247A (en) | Chinese medicine for treating cardiovascular and cerebrovascular disease | |
| CN1319557C (en) | Chinese medicine composition for treating cardiac and cerebral vascular diseases and its prepn | |
| CN1270767C (en) | Medicine for treating vasculitis, scleriasis and arteriosclerosis type lower limb vascular occlusion | |
| CN1919252A (en) | Medicine for treating cardiovascular and cerebrovascular disease | |
| CN1919238A (en) | Medicine for treating cardiovascular and cerebrovascular disease | |
| CN1919237A (en) | Medicine for treating cardiovascular and cerebrovascular diseases | |
| CN1919239A (en) | Traditional medicine composition for treating cardiovascular and cerebrovascular diseases | |
| CN1514242A (en) | Quality control method of injection agent for treating apoplexia | |
| CN1323688C (en) | Medicine composition for treating prostatosis and method for preparing the same | |
| CN1919242A (en) | Traditional Chinese medicine composition for treating cardiac and cerebral vascular disease | |
| CN1296060C (en) | Compound ginkgo leaf reparation and its making method | |
| CN1919236A (en) | Medicine for treating cardiovascular and cerebrovascular diseases | |
| CN1919235A (en) | Cardiac and cerebral vascular disease treating pharmaceutical composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: TASLY PHARMACEUTICAL GROUP CO., LTD. Free format text: FORMER NAME: TIANJIN TASLY PHARM. CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 300402 Tianjin City, Beichen science and Technology Park of Beichen Xinyi Road Liaohe Road No. 1 white Patentee after: TASLY PHARMACEUTICAL GROUP Co.,Ltd. Address before: 300402 Tianjin City, Beichen science and Technology Park of Beichen Xinyi Road Liaohe Road No. 1 white Patentee before: TIANJIN TASLY PHARMACEUTICAL Co.,Ltd. |
|
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 300402 Tianjin City, Beichen science and Technology Park of Beichen Xinyi Road Liaohe Road No. 1 white Patentee after: TASLY PHARMACEUTICAL GROUP Co.,Ltd. Address before: 300402 Tianjin City, Beichen science and Technology Park of Beichen Xinyi Road Liaohe Road No. 1 white Patentee before: TASLY PHARMACEUTICAL GROUP Co.,Ltd. |
|
| CX01 | Expiry of patent term | ||
| CX01 | Expiry of patent term |
Granted publication date: 20080723 |