CN1919250A - Traditional Chinese medicinal formulation for treating cardiovascular and cerebrovascular disease - Google Patents
Traditional Chinese medicinal formulation for treating cardiovascular and cerebrovascular disease Download PDFInfo
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- CN1919250A CN1919250A CN 200510014853 CN200510014853A CN1919250A CN 1919250 A CN1919250 A CN 1919250A CN 200510014853 CN200510014853 CN 200510014853 CN 200510014853 A CN200510014853 A CN 200510014853A CN 1919250 A CN1919250 A CN 1919250A
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Abstract
The invention discloses a Chinese medicinal composition for treating cardiovascular and cerebrovascular diseases, which is prepared from red sage root extract 60.0-95.0%, pseudo-ginseng leaf glycoside extract 2.5-25.0%, and natural borneol or rosewood oil 2.5-15.0%. The content of danshensu in the salvia miltiorrhizae extract is 3-10%, the content of total savianolic acid is 50-75%, the content of salvianolic acid B is 20-45%, the content of total saponins in pseudo-ginseng leaf glycoside extract is 70-98%. The composition has evident functions in resisting cerebral ischemia and myocardial ischemia, the curative effect is better than the application of single extract of red sage root or pseudo-ginseng leaf glycosides, thus providing a more effective and more convenient Chinese medicinal composition of significant portions and preparation clinically.
Description
Technical field
The present invention relates to a kind of Chinese medicine composition for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof.
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 though die from the cardiovascular and cerebrovascular disease every year has the part patient to survive through rescue in addition, 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, compound red sage root preparation occupies important position, is 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. also more and more is subject to people's attention in addition 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, the great demand that has drug combination clinically, therefore, the compound red sage root preparation with the effective site preparation will have characteristics such as dosage is little, good effect, steady quality, broad market prospect.
Summary of the invention
The purpose of this invention is to provide little Chinese medicine composition efficiently of a kind of amount and preparation thereof.
Another object of the present invention provides the preparation method of said composition and preparation thereof.
The present invention is implemented by following technical proposals.
Effective ingredient in Chinese compositions of the present invention comprises following component by weight percentage:
Radix Salviae Miltiorrhizae extract 60.0%～95.0%
Folium Notoginseng glycoside extract 2.5%～25.0%
Natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 2.5%～15.0%
Effective ingredient in Chinese compositions of the present invention more preferably comprises following component by weight percentage:
Radix Salviae Miltiorrhizae extract 75.0%～90.0%
Folium Notoginseng glycoside extract 6.0%～15.0%
Natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 4.0%～10.0%
Effective ingredient in Chinese compositions of the present invention, best for comprising following component by weight percentage:
Radix Salviae Miltiorrhizae extract 80%
Folium Notoginseng glycoside extract 13%
Natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 7%
Above-mentioned Radix Salviae Miltiorrhizae extract obtains with following method: get the Radix Salviae Miltiorrhizae of salvia piece or pulverizing, decoct with water or supersound extraction 2～3 times, add 5～7 times of water gagings of medical material weight, each 0.5～2 hour at every turn; Merge extractive liquid, is 1.5～4 with acid for adjusting pH, puts coldly, filters; The resin volume is equivalent to the macroporous resin column of 2～4 times of crude drugs on the filtrate, and with 1-1.5 times of cylinder hydrops flushing, water lotion discards earlier, and 85～95% ethanol elutions of 2～3 times of column volumes of reuse are collected eluent; The eluent concentrating under reduced pressure, drying promptly gets Radix Salviae Miltiorrhizae extract.The content of Danshensu of this Radix Salviae Miltiorrhizae extract is 3%～10%, and Radix Salviae Miltiorrhizae total phenolic acids content is 50%～75%, and content of danshinolic acid B is 20%～45%.
Above-mentioned macroporous resin is the macroporous resin of nonpolar or low pole, is preferably D101, AB-8 or ZTC type macroporous resin, and the best is an AB-8 type macroporous resin.
Above-mentioned content of Danshensu assay method is referring to Chinese patent CN1520307A, and Radix Salviae Miltiorrhizae total phenolic acids assay and content of danshinolic acid B are measured referring to Chinese patent CN1600318A.
Above-mentioned Folium Notoginseng glycoside extract can obtain with following method: get Folium Notoginseng, pulverize, soak, transfer pH3～5.5 with acid, the amount that adds 5～15U with every gram crude drug adds cellulase, fully stirs, and puts 30～60 ℃ of water-bath 2～4h, and extracting solution is standby; Extracting the back residue adds water again or adds that 10%～90% alcohol heating reflux extracts or supersound extraction 1～3 time, extracting solution before and after merging; Extracting solution is evaporated to 1～3 times of amount of medical material volume, and clear liquor or filtrate are got in centrifugal or filtration; Clear liquor or filtrate are gone up anion-exchange resin column, with 40%～70% ethanol elution, collect eluent; Macroporous resin column on the eluent, first water flushing, reuse 40～70% ethanol elutions are collected ethanol elution; The eluent concentrating under reduced pressure, drying gets the Folium Notoginseng glycoside extract.Upper prop order in the above-mentioned Folium Notoginseng glycoside method for preparing extractive can be changed, be that the also available following method of Folium Notoginseng glycoside extract obtains: get Folium Notoginseng, pulverize, soak, transfer pH3～5.5 with acid, the amount that adds 5～15U with every gram crude drug adds cellulase, fully stirs, put 30～60 ℃ of water-bath 2～4h, extracting solution is standby; Extracting the back residue adds water again or adds that 10%～90% alcohol heating reflux extracts or supersound extraction 1～3 time, extracting solution before and after merging; Extracting solution is evaporated to 1～3 times of amount of medical material volume, and clear liquor or filtrate are got in centrifugal or filtration; Clear liquor or filtrate are gone up macroporous resin column, first water flushing, and reuse 40～70% ethanol elutions are collected ethanol elution; Anion-exchange resin column on the ethanol elution with 40%～70% ethanol elution, is collected eluent; The eluent concentrating under reduced pressure, drying gets the Folium Notoginseng glycoside extract.Arasaponin R1 content is 12%～30% in this Folium Notoginseng glycoside extract, and ginsenoside Rg1's content is 4%～15%, and ginsenoside Rb1's content is 25%～50%, and its total saponin content is 70%～98%; The best is 80%～98% for total saponin content.
Above-mentioned macroporous resin is the macroporous resin of nonpolar or low pole, is preferably D101, AB-8 or ZTC type macroporous resin, and the best is an AB-8 type macroporous resin.Above-mentioned anion exchange resin is a weak-base anion-exchange resin, and the best is a D-941 ion exchange resin.
Above-mentioned Folium Notoginseng glycoside extract also can be buied from market, as long as saponin content reaches above-mentioned standard.
The content of the total saponins of above-mentioned Folium Notoginseng glycoside extract is measured with reference to spectrophotography (in the ginsenoside Rb1) in the following document: " the Folium Notoginseng glycoside content assaying method relatively ", GUIHAIA.1996，16(3)：287-291。
Arasaponin R1, ginsenoside Rg1, ginsenoside Rb1's content assaying method is seen Chinese patent CN1600318A in the above-mentioned Folium Notoginseng glycoside extract.
Natural Broneolum Syntheticum in the above-mentioned Chinese medicine composition should meet the Chinese Pharmacopoeia standard.Natural Broneolum Syntheticum can replace with the Borneolum Syntheticum that meets the Chinese Pharmacopoeia standard.
Lignum Dalbergiae Odoriferae oil in the above-mentioned Chinese medicine composition is that the Lignum Dalbergiae Odoriferae medical material is through the distillation gained.
Effective ingredient in Chinese compositions 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 aqueous injection, tablet, slow releasing tablet, drop pill, granule, injectable powder, capsule, microgranule.Preferred dosage form is drop pill, injectable powder.
The preparation of Chinese medicine composition composition dropping pills of the present invention: get above-mentioned Radix Salviae Miltiorrhizae extract, Folium Notoginseng glycoside extract and natural Broneolum Syntheticum (or Lignum Dalbergiae Odoriferae oil) to scale, Polyethylene Glycol-6000 or Polyethylene Glycol-4000 or both mixture mix homogeneously with 2～4 times of medicine gross weights, heating and melting, move in the dropping-pill machine jar after changing material, in medicine liquid droplet to 6～8 ℃ liquid paraffin or the methyl-silicone oil, oil removing, promptly.
The preparation of Chinese medicine composition injectable powder of the present invention: get above-mentioned Radix Salviae Miltiorrhizae extract, Folium Notoginseng glycoside extract and natural Broneolum Syntheticum to scale, add an amount of adjuvant and distilled water, the mixing postlyophilization, promptly.
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 of Chinese medicine composition of the present invention, Radix Salviae Miltiorrhizae extract, Folium Notoginseng glycoside extract to rat model nervous symptoms and cerebral infarction scope.The result shows that Chinese medicine composition of the present invention has tangible treating cerebral ischemia, and its curative effect is better than using separately Radix Salviae Miltiorrhizae extract or Folium Notoginseng glycoside extract, shows that Chinese medicine composition of the present invention has 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 extract of embodiment one, the Folium Notoginseng glycoside extract of embodiment one.
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, 1M K rapidly the brain sheet to be placed the TTC dye liquor
2HPO
40.1ml 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)
| Group | Dosage (mg/kg) | Number of animals | Nervous symptoms scoring in 6 hours | Nervous symptoms scoring in 24 hours |
| The notoginseng leaf triterpenes extract model group of the Salvia root P.E embodiment one of the Chinese medicine composition embodiment one of the Chinese medicine composition embodiment two of embodiment one | 20 20 20 20 | 10 10 10 10 10 | 2.29±0.45** #& 2.21±0.39** #& 2.78±0.52* 2.81±0.44* 3.23±0.41 | 2.03±0.41** #& 2.06±0.37** #& 2.46±0.41* 2.56±0.43* 3.01±0.48 |
Annotate: compare * P＜0.05, * * P＜0.01 with model group; Compare with the Radix Salviae Miltiorrhizae extract group,
#P＜0.05,
##P＜0.01; Compare with Folium Notoginseng glycoside extract group,
﹠amp;P＜0.05,
﹠amp; ﹠amp;P＜0.01
Several Chinese medicine extract of table 2 are to the influence of MCAO rat cerebral infarction scope (x ± s)
| Group | Dosage (mg/kg) | Number of animals | Infraction heavily accounts for full brain % | Infraction heavily accounts for half brain % |
| The notoginseng leaf triterpenes extract model group of the Salvia root P.E embodiment one of the Chinese medicine composition embodiment one of the Chinese medicine composition embodiment two of embodiment one | 20 20 20 20 | 10 10 10 10 10 | 2.52±0.65** #& 2.57±0.68** #& 3.31±0.84* 3.34±0.81* 4.33±0.76 | 4.58±1.34** #& 4.61±1.33** #& 6.19±1.62* 6.29±1.65* 8.21±1.54 |
Annotate: compare * P＜0.05, * * P＜0.01 with model group; Compare with the Radix Salviae Miltiorrhizae extract group,
#P＜0.05,
##P＜0.01; Compare with Folium Notoginseng glycoside extract group,
﹠amp;P＜0.05,
﹠amp; ﹠amp;P＜0.01
The result of above table 1 and table 2 shows that each administration group all has tangible treating cerebral ischemia, and the curative effect of the present composition is best.
The present invention adopts rat experiment myocardial infarction model and external perfusion method, has compared the function of resisting myocardial ischemia of Chinese medicine composition of the present invention, Radix Salviae Miltiorrhizae extract, Folium Notoginseng glycoside extract.The result shows that Chinese medicine composition of the present invention has tangible function of resisting myocardial ischemia, and its curative effect is better than using separately Radix Salviae Miltiorrhizae extract or Folium Notoginseng glycoside extract, shows that Chinese medicine composition of the present invention has 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 Radix Salviae Miltiorrhizae extract group of embodiment two; The Folium Notoginseng glycoside extract group of embodiment two; 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)
| Group | Dosage (mg/kg) | Number of animals | Infarcted region/ventricle (%) | Infarcted region/heart (%) |
| The Folium Notoginseng glycoside extract model group of the Radix Salviae Miltiorrhizae extract embodiment two of the Chinese medicine composition embodiment two of the Chinese medicine composition embodiment two of embodiment one | 20 20 20 20 | 10 10 10 10 10 | 17.24±5.97** #& 17.67±6.34** #& 24.56±7.85* 26.11±7.89* 34.35±7.54 | 15.87±4.81** #& 15.65±4.52** #& 20.24±4.39* 20.82±4.12* 25.62±5.59 |
Annotate: compare * P＜0.05, * * P＜0.01 with model group; Compare with the Radix Salviae Miltiorrhizae extract group,
#P＜0.05,
##P＜0.01; Compare with Folium Notoginseng glycoside extract group,
﹠amp;P＜0.05,
﹠amp; ﹠amp;P＜0.01
(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)
| Group | Dosage (mg/ml) | Coronary flow value added (ml/min) | Heart rate attenuating value (inferior/min) |
| The Folium Notoginseng glycoside extract of the Radix Salviae Miltiorrhizae extract embodiment two of the Chinese medicine composition embodiment two of the Chinese medicine composition embodiment two of embodiment one | 20 20 20 20 | 10.26±1.55** ## 10.34±1.52** ## 7.31±1.24 7.26±1.43 | 19±11* 19±12*# 9±4 9±4 |
Annotate: compare * P＜0.05, * * P＜0.01 with the Radix Salviae Miltiorrhizae extract group; Compare with Folium Notoginseng glycoside extract group,
#P＜0.05,
##P＜0.01.
The result of above table 3 and table 4 shows that each administration group all has tangible function of resisting myocardial ischemia, and the curative effect of the present composition is best.
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
The preparation of Radix Salviae Miltiorrhizae extract: get the Radix Salviae Miltiorrhizae of salvia piece or pulverizing, decoct with water 2 times, add 6.5 times of water gagings of medical material weight, each 2 hours at every turn; Merge extractive liquid, is 2 with acid for adjusting pH, puts coldly, filters; The resin volume is equivalent to AB-8 type macroporous resin (production of Tianjin resin processing plant of the Nankai University) post of 3 times of crude drugs on the filtrate, and with 1.5 times of cylinder hydrops flushings, water lotion discards earlier, and 95% ethanol elution of 2.5 times of column volumes of reuse is collected eluent; Eluent is evaporated to extractum proportion 1.15, and drying under reduced pressure promptly gets Radix Salviae Miltiorrhizae extract.The content of Danshensu 4.5% of this Radix Salviae Miltiorrhizae extract, total phenolic content 57.1%, content of danshinolic acid B 27.5%.
The preparation of Folium Notoginseng glycoside extract: get Folium Notoginseng, pulverize, add the water logging bubble of 3 times of amounts of crude drug weight, transfer pH4.0 with acid, the amount that adds 10U with every gram crude drug adds cellulase, fully stirs, and puts 40 ℃ of water-bath 3h, and extracting solution is standby; Extracting the back residue and add water again 90 ℃ of following reflux, extract, twice, is 7 times of water gagings of crude drug weight for the first time, is for the second time 6 times of amount crude drug weight water, and each 2 hours, extracting solution before and after merging discarded residue; Extracting solution is evaporated to 1 times of amount of medical material volume at 70 ℃, filters; The filtrate thin up is to 2 times of amounts of medical material volume, and is centrifugal, gets clear liquor; D-941 ion exchange resin on the clear liquor (the anti-resin in Shandong, Shandong subsidiary factory) post with 2.5 times of amounts of medical material volume, 50% ethanol elution, is collected eluent; Eluent is gone up AB-8 type macroporous resin (production of Tianjin resin processing plant of Nankai University) post again, with the water flushing of 4 times of amounts of medical material volume, discards earlier, and 50% ethanol elution of 4 times of amounts of reuse medical material volume is collected ethanol elution; It is 1.15 extractum that eluent is evaporated to proportion in 70 ℃, drying, the Folium Notoginseng glycoside extract, its total saponin content is 81.4%, arasaponin R1 content is 18.2%, ginsenoside Rg1's content is 8.5%, ginsenoside Rb1's content is 36.7%.
Get above-mentioned Radix Salviae Miltiorrhizae extract 5.6g, above-mentioned Folium Notoginseng glycoside extract 0.9g, natural Broneolum Syntheticum 0.5g, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment two
The preparation of Radix Salviae Miltiorrhizae extract: get the Radix Salviae Miltiorrhizae of salvia piece or pulverizing, add the water supersound extraction 2 times, add 6 times of water gagings of medical material weight, each 40 minutes at every turn; Merge extractive liquid, is 2.5 with acid for adjusting pH, puts coldly, filters; The resin volume is equivalent to D101 type macroporous resin (production of Tianjin resin processing plant of the Nankai University) post of 3 times of crude drugs on the filtrate, and with 1.0 times of cylinder hydrops flushings, water lotion discards earlier, and 95% ethanol elution of 3 times of column volumes of reuse is collected eluent; Eluent is evaporated to extractum proportion 1.15, and drying under reduced pressure promptly gets Radix Salviae Miltiorrhizae extract.The content of Danshensu 4.6% of this Radix Salviae Miltiorrhizae extract, total phenolic content 54.6%, content of danshinolic acid B 26.4%.
The preparation of Folium Notoginseng glycoside extract: get Folium Notoginseng, pulverize, add the water logging bubble of 3.5 times of amounts of crude drug weight, transfer pH4.5 with acid, the amount that adds 12U with every gram crude drug adds cellulase, fully stirs, and puts 40 ℃ of water-bath 3h, and extracting solution is standby; Extracting the back residue and add 75% ethanol again 90 ℃ of following reflux, extract, twice, is 75% ethanol of 7 times of amounts of crude drug weight for the first time, is for the second time 6 times of amount 75% ethanol, and each 2 hours, extracting solution before and after merging discarded residue; Extracting solution is evaporated to 2 times of amounts of medical material volume at 70 ℃, filters; D-941 ion exchange resin on the filtrate (the anti-resin in Shandong, Shandong subsidiary factory) post with 2.5 times of amounts of medical material volume, 60% ethanol elution, is collected eluent; Eluent is gone up D101 type macroporous resin (production of Tianjin resin processing plant of Nankai University) post again, with the water flushing of 4 times of amounts of medical material volume, discards earlier, and 60% ethanol elution of 4 times of amounts of reuse medical material volume is collected ethanol elution; It is 1.15 extractum that eluent is evaporated to proportion in 70 ℃, drying, the Folium Notoginseng glycoside extract, its total saponin content is 80.9%, arasaponin R1 content is 17.4%, ginsenoside Rg1's content is 8.1%, ginsenoside Rb1's content is 35.6%.
Get above-mentioned Radix Salviae Miltiorrhizae extract 5.6g, above-mentioned Folium Notoginseng glycoside extract 0.9g, Lignum Dalbergiae Odoriferae oil 0.5g, add 9.0g Polyethylene Glycol-6000 mix homogeneously, fusion gets Chinese medicine composition after the cooling.
Embodiment three
The preparation of Radix Salviae Miltiorrhizae extract: get the Radix Salviae Miltiorrhizae of salvia piece or pulverizing, decoct with water 2 times, add 6.5 times of water gagings of medical material weight, each 2 hours at every turn; Merge extractive liquid, is 2 with acid for adjusting pH, puts coldly, filters; The resin volume is equivalent to ZTC type macroporous resin (production of Tianjin resin processing plant of the Nankai University) post of 3 times of crude drugs on the filtrate, and with 1.5 times of cylinder hydrops flushings, water lotion discards earlier, and 95% ethanol elution of 2.5 times of column volumes of reuse is collected eluent; Eluent is evaporated to extractum proportion 1.12, and drying under reduced pressure promptly gets Radix Salviae Miltiorrhizae extract.The content of Danshensu 4.1% of this Radix Salviae Miltiorrhizae extract, total phenolic content 53.6%, content of danshinolic acid B 24.8%.
The preparation of Folium Notoginseng glycoside extract: get Folium Notoginseng, pulverize, add the water logging bubble of 3.5 times of amounts of crude drug weight, transfer pH4.5 with acid, the amount that adds 10U with every gram crude drug adds cellulase, fully stirs, and puts 40 ℃ of water-bath 3.5h, and extracting solution is standby; Extracting the back residue and add water again 90 ℃ of following supersound extraction twice, is 7 times of water gagings of crude drug weight for the first time, is 6 times of water gagings for the second time, and each 30 minutes, extracting solution before and after merging discarded residue; Extracting solution is evaporated to 2 times of amounts of medical material volume at 70 ℃, and is centrifugal; AB-8 type macroporous resin on the clear liquor (production of Tianjin resin processing plant of Nankai University) post with the water flushing of 4 times of amounts of medical material volume, discards earlier, and 65% ethanol elution of 4 times of amounts of reuse medical material volume is collected ethanol elution; Eluent is gone up D-941 ion exchange resin (the anti-resin in Shandong, Shandong subsidiary factory) post again, with 2.5 times of amounts of medical material volume, 65% ethanol elution, collects eluent; It is 1.15 extractum that eluent is evaporated to proportion in 70 ℃, drying, the Folium Notoginseng glycoside extract, its total saponin content is 80.3%, arasaponin R1 content is 17.9%, ginsenoside Rg1's content is 8.1%, ginsenoside Rb1's content is 36.2%.
Get above-mentioned Radix Salviae Miltiorrhizae extract 6.8g, above-mentioned Folium Notoginseng glycoside extract 0.8g, natural Broneolum Syntheticum 0.5g, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment four
Get Folium Notoginseng glycoside extract 1.0g, the natural Broneolum Syntheticum 0.4g of Radix Salviae Miltiorrhizae extract 5.7g, the embodiment two of embodiment one, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment five
Get Folium Notoginseng glycoside extract 0.8g, the Borneolum Syntheticum 0.5g of Radix Salviae Miltiorrhizae extract 5.1g, the embodiment three of embodiment one, mix homogeneously, lyophilization gets Chinese medicine composition.
Embodiment six
Get Folium Notoginseng glycoside extract 0.8g, the Lignum Dalbergiae Odoriferae oil 0.4g of Radix Salviae Miltiorrhizae extract 8.9g, the embodiment two of embodiment two, add 12.0g Polyethylene Glycol-6000 mix homogeneously, fusion gets Chinese medicine composition after the cooling.
Embodiment seven
Get Folium Notoginseng glycoside extract 0.9g, the natural Broneolum Syntheticum 0.5g of Radix Salviae Miltiorrhizae extract 5.6g, the embodiment one of embodiment one, with 18.5g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment eight
Get Folium Notoginseng glycoside extract 0.8g, the natural Broneolum Syntheticum 0.5g of Radix Salviae Miltiorrhizae extract 6.2g, the embodiment two of embodiment two, with 18.0g Polyethylene Glycol-4000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment nine
Get Folium Notoginseng glycoside extract 1.0g, the natural Broneolum Syntheticum 0.5g of Radix Salviae Miltiorrhizae extract 5.2g, the embodiment one of embodiment three, with 19.0g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ methyl-silicone oil of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment ten
Get Folium Notoginseng glycoside extract 0.9g, the natural Broneolum Syntheticum 0.5g of Radix Salviae Miltiorrhizae extract 6.8g, the embodiment two of embodiment one, with 3.5g Polyethylene Glycol-4000 and 14.0g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment 11
Get Folium Notoginseng glycoside extract 0.8g, the natural Broneolum Syntheticum 0.5g of Radix Salviae Miltiorrhizae extract 7.9g, the embodiment one of embodiment three, with 16.5g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment 12
Get Folium Notoginseng glycoside extract 0.8g, the Borneolum Syntheticum 0.4g of Radix Salviae Miltiorrhizae extract 6.5g, the embodiment two of embodiment three, with 17.5g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment 13
Get Folium Notoginseng glycoside extract 0.9g, the Lignum Dalbergiae Odoriferae oil 0.5g of Radix Salviae Miltiorrhizae extract 5.6g, the embodiment one of embodiment one, with 18.5g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ methyl-silicone oil of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment 14
Get Folium Notoginseng glycoside extract 0.8g, the Lignum Dalbergiae Odoriferae oil 0.5g of Radix Salviae Miltiorrhizae extract 6.2g, the embodiment two of embodiment two, with 3.5g Polyethylene Glycol-4000 and 14.5g Polyethylene Glycol-6000 mix homogeneously, heating and melting, move in the dropping-pill machine jar after changing material, in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing makes 1000 of drop pill.
Embodiment 15
Get Folium Notoginseng glycoside extract 2.5g, natural Broneolum Syntheticum 1.2g, mannitol 5.5g, calcium disodium edetate 0.9g and the distilled water 1ml of Radix Salviae Miltiorrhizae extract 16.4g, the embodiment one of embodiment one, behind the said components mixing, lyophilization, 1000 of packing, promptly.
Embodiment 16
Get Folium Notoginseng glycoside extract 2.9g, natural Broneolum Syntheticum 1.2g, low molecular dextran 5.5g, calcium disodium edetate 0.9g and the distilled water 1ml of Radix Salviae Miltiorrhizae extract 15.7g, the embodiment two of embodiment two, behind the said components mixing, lyophilization, 1000 of packing, promptly.
Embodiment 17
Get Folium Notoginseng glycoside extract 1.9g, Borneolum Syntheticum 1.2g, glucose 5.5g, sodium thiosulfate 0.9g and the distilled water 1ml of Radix Salviae Miltiorrhizae extract 16.7g, the embodiment one of embodiment three, behind the said components mixing, lyophilization, 1000 of packing, promptly.
Embodiment 18
Get Lignum Dalbergiae Odoriferae oil 1.5g, join in the saturated hydroxypropyl solution of 13ml, stirring and dissolving filters, the filtrate cold drying, the clathrate powder of Lignum Dalbergiae Odoriferae oil and hydroxypropyl.Except that the clathrate powder of above-mentioned Lignum Dalbergiae Odoriferae oil and hydroxypropyl, get Folium Notoginseng glycoside extract 2.5g, mannitol 5.5g, calcium disodium edetate 0.9g and the distilled water 2ml of Radix Salviae Miltiorrhizae extract 16.7g, the embodiment one of embodiment one again, behind the said components mixing, lyophilization, 1000 of packing, promptly.
Embodiment 19
Get Folium Notoginseng glycoside extract 1.2g, the Borneolum Syntheticum 0.8g of Radix Salviae Miltiorrhizae extract 12.5g, the embodiment one of embodiment one, with 210g 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 24g Pulvis Talci, mixing fills in 1000 capsules, promptly.
Embodiment 20
Get Folium Notoginseng glycoside extract 1.2g, the natural Broneolum Syntheticum 0.8g of Radix Salviae Miltiorrhizae extract 12.5g, the embodiment two of embodiment one,, be pressed into 1000, promptly with 64g microcrystalline Cellulose and 20g magnesium stearate mix homogeneously.
Claims (10)
1. Chinese medicine composition for the treatment of cardiovascular and cerebrovascular disease, form by following component by weight percentage:
Radix Salviae Miltiorrhizae extract 60.0%～95.0%,
Folium Notoginseng glycoside extract 2.5%～25.0%,
Natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 2.5%～15.0%;
Wherein the content of Danshensu of Radix Salviae Miltiorrhizae extract is 3%～10%, and Radix Salviae Miltiorrhizae total phenolic acids content is 50%～75%, and content of danshinolic acid B is 20%～45%; The total saponin content of Folium Notoginseng glycoside extract is 70%～98%.
2. according to the described Chinese medicine composition of claim 1, it is characterized in that the percentage by weight of described each component is:
Radix Salviae Miltiorrhizae extract 75.0%～90.0%,
Folium Notoginseng glycoside extract 6.0%～15.0%,
Natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 4.0%～10.0%;
Wherein the content of Danshensu of Radix Salviae Miltiorrhizae extract is 3%～10%, and Radix Salviae Miltiorrhizae total phenolic acids content is 50%～75%, and content of danshinolic acid B is 20%～45%; The total saponin content of Folium Notoginseng glycoside extract is 70%～98%.
3. according to the described Chinese medicine composition of claim 1, it is characterized in that the percentage by weight of described each component is:
Radix Salviae Miltiorrhizae extract 80%,
Folium Notoginseng glycoside extract 13%,
Natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 7%;
Wherein the content of Danshensu of Radix Salviae Miltiorrhizae extract is 3%～10%, and Radix Salviae Miltiorrhizae total phenolic acids content is 50%～75%, and content of danshinolic acid B is 20%～45%; The total saponin content of Folium Notoginseng glycoside extract is 70%～98%.
4. according to the described Chinese medicine composition of the arbitrary claim of claim 1～3, it is characterized in that, arasaponin R1 content is 12%～30% in the described Folium Notoginseng glycoside extract, ginsenoside Rg1's content is 4%～15%, ginsenoside Rb1's content is 25%～50%, and the content of its total saponins is 80%～98%.
5. according to the described Chinese medicine composition of the arbitrary claim of claim 1～3, it is characterized in that described Radix Salviae Miltiorrhizae extract is prepared by following method: get the Radix Salviae Miltiorrhizae of salvia piece or pulverizing, decoct with water or supersound extraction 2～3 times, add 5～7 times of water gagings of medical material weight, each 0.5～2 hour at every turn; Merge extractive liquid, is 1.5～4 with acid for adjusting pH, puts coldly, filters; The resin volume is equivalent to the macroporous resin column of 2～4 times of crude drugs on the filtrate, and with 1～1.5 times of cylinder hydrops flushing, water lotion discards earlier, and 85～95% ethanol elutions of 2～3 times of column volumes of reuse are collected eluent; The eluent concentrating under reduced pressure, drying promptly gets Radix Salviae Miltiorrhizae extract.
6. Chinese medicine composition according to claim 5 is characterized in that, described macroporous resin is D101, AB-8 or ZTC type macroporous resin.
7. according to the described Chinese medicine composition of the arbitrary claim of claim 1～3, it is characterized in that, described Folium Notoginseng glycoside extract is prepared by following method: get Folium Notoginseng, pulverize, soak, transfer pH3～5.5 with acid, the amount that adds 5～15U with every gram crude drug adds cellulase, fully stir, put 30～60 ℃ of water-bath 2～4h, extracting solution is standby; Extracting the back residue adds water again or adds that 10%～90% alcohol heating reflux extracts or supersound extraction 1～3 time, extracting solution before and after merging; Extracting solution is evaporated to 1～3 times of amount of medical material volume, and clear liquor or filtrate are got in centrifugal or filtration; Clear liquor or filtrate are gone up anion-exchange resin column, with 40%～70% ethanol elution, collect eluent; Macroporous resin column on the eluent, first water flushing, reuse 40～70% ethanol elutions are collected ethanol elution; The eluent concentrating under reduced pressure, drying gets the Folium Notoginseng glycoside extract.
8. Chinese medicine composition according to claim 7 is characterized in that, described anion exchange resin is a D-941 ion exchange resin; Described macroporous resin is D101, AB-8 or ZTC type macroporous resin.
9. be the drop pill that active component is made according to the described Chinese medicine composition of the arbitrary claim of claim 1～3, it is characterized in that, described drop pill is prepared from by following method: get above-mentioned Radix Salviae Miltiorrhizae extract, Folium Notoginseng glycoside extract and natural Broneolum Syntheticum or Lignum Dalbergiae Odoriferae oil to scale, Polyethylene Glycol-6000 or Polyethylene Glycol-4000 or both mixture mix homogeneously with 2～4 times of medicine gross weights, heating and melting, move in the dropping-pill machine jar after changing material, in medicine liquid droplet to 6～8 ℃ liquid paraffin or the methyl-silicone oil, oil removing, promptly.
10. be the injectable powder that active component is made according to the described Chinese medicine composition of the arbitrary claim of claim 1～3.
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| CN102247435A (en) * | 2011-08-06 | 2011-11-23 | 叶耀良 | Preparation for promoting blood circulation by removing blood stasis and regulating flow of qi to alleviate pain, and preparation process thereof |
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| CN100404035C (en) * | 2003-09-23 | 2008-07-23 | 天津天士力制药股份有限公司 | Combination of Chinese traditional medicine for curing cardiovascular diseases and cerebrovascular disease |
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