CN101181418A - Medicine composition for curing arrhythmia and preparation method thereof - Google Patents
Medicine composition for curing arrhythmia and preparation method thereof Download PDFInfo
- Publication number
- CN101181418A CN101181418A CNA2007100191615A CN200710019161A CN101181418A CN 101181418 A CN101181418 A CN 101181418A CN A2007100191615 A CNA2007100191615 A CN A2007100191615A CN 200710019161 A CN200710019161 A CN 200710019161A CN 101181418 A CN101181418 A CN 101181418A
- Authority
- CN
- China
- Prior art keywords
- adds
- water
- filtrate
- herba
- hours
- 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
Landscapes
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a drug combination which cures arrhythmia and a production method. The drug combination is produced by red ginseng, epimedium, fructus psoraleae (stir-frying with salt-water), medlar, ma-huang, asarum, salvia miltiorrhiza and bloodsucker. The granule types comprise grain granule, hard capsule granule, soft capsule granule, troche, drop pill, pill and oral liquid preparation. The invention aims at providing a drug curing the arrhythmia, not only has accurate curative effects, but also better improves clinic symptoms, shortens the treatment period and prevents recrudescence.
Description
Technical field
The present invention relates to a kind of Chinese medicine preparation, especially relate to ARR Chinese medicine preparation of a kind of treatment and preparation method thereof.
Background technology
Sick sinus syndrome (being called for short the disease hole) and sinus bradycardia (it is slow to be called for short hole) are common cardiac arrhythmias.The traditional Chinese medical science think disease hole and hole slow be by deficiency of heart-YANG and kidney-YANG, the cold coagulation blood vessels cause, should temperature compensation heart kidney, blood circulation promoting and blood stasis dispelling.On November 16th, 2000 Chinese patent gazette to disclose denomination of invention be 1354004 patent application for " Chinese medicine composition of treatment sick sinus syndrome ", publication number, make by Radix Ginseng, Radix Ophiopogonis, Radix Aconiti Lateralis Preparata, Herba Epimedii, Herba Cistanches, Ramulus Cinnamomi, Radix Et Rhizoma Nardostachyos, Herba Asari, Herba Ephedrae, Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, but QI invigorating YANG invigorating deficiency, effect is not ideal enough.
Summary of the invention
The purpose of this invention is to provide slow ARR new Chinese medicine of type of sick hole of a kind of treatment and hole and preparation method thereof, remove patient's sufferings, create good society and economic benefit.
Drug regimen raw material of the present invention is by weight ratio: Radix Ginseng Rubra 50～150, Herba Epimedii 125～375, Fructus Psoraleae (salt is processed) 375～1125, Fructus Lycii 125～375, Herba Ephedrae 125～375, Herba Asari 25～75, Radix Salviae Miltiorrhizae 200～550, Hirudo 125～375.Wherein preferred Radix Ginseng Rubra 75～125, Herba Epimedii 150～300, Fructus Psoraleae (salt is processed) 400～950, Fructus Lycii 150～300, Herba Ephedrae 150～300, Herba Asari 40-60, Radix Salviae Miltiorrhizae 300～450, Hirudo 150～300.Most preferably Radix Ginseng Rubra 100, Herba Epimedii 250, Fructus Psoraleae (salt is processed) 750, Fructus Lycii 250, Herba Ephedrae 250, Herba Asari 50, Radix Salviae Miltiorrhizae 375, Hirudo 250.Make hard capsule, tablet, granule, soft capsule, drop pill, pill, oral liquid etc. with above-mentioned raw materials by the method for accepting on the pharmaceutics, wherein be preferably oral liquid.
Above preparation of drug combination method is: Herba Asari adds 5～10 times in water, and vapor distillation extracted 4～8 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 2～6 times of beta-schardinger dextrin-s, adds 1～3 times in water, grinds 30 minutes, and low temperature (40～60 ℃) drying is ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 55%～90% alcohol reflux three times, and each 1～2 hour, filter, merging filtrate reclaims ethanol.6 flavors such as all the other Herba Epimedii add 8～12 times in water, decoct three times, each 1～2 hour, decoction liquor and above-mentioned two kinds of filtrates merge, filter, concentrated (30～60 ℃) to the relative density of filtrate decompression is 1.10～1.20 clear paste, adds above-mentioned Benexate Hydrochloride, mixing adds proper auxiliary materials again and makes different dosage form.
Wherein the preferred for preparation method is: Herba Asari adds 6 times in water, and vapor distillation extracted 6 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 3 times of beta-schardinger dextrin-s, adds 2 times in water, grinds 30 minutes, and low temperature (50 ℃) drying is ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 75% alcohol reflux three times, and each 1.5 hours, filter, merging filtrate reclaims ethanol.6 flavors such as all the other Herba Epimedii add 10 times in water, decoct each 1 hour three times, decoction liquor and above-mentioned two kinds of filtrates merge, and filter, and filtrate decompression concentrated (40 ℃) is 1.20 clear paste to relative density, add above-mentioned Benexate Hydrochloride, mixing adds proper auxiliary materials again and makes different dosage form.
Adjuvant among the present invention can be acceptable any excipient or a carrier on the pharmaceutics.
The preparation method of hard capsule of the present invention: Herba Asari adds 6 times in water, and vapor distillation extracted 6 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 3 times of beta-schardinger dextrin-s, adds 2 times in water, grinds 30 minutes, and low temperature (50 ℃) drying is ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 75% alcohol reflux three times, and each 1.5 hours, filter, merging filtrate reclaims ethanol.6 flavors such as all the other Herba Epimedii add 10 times in water, decoct three times, and each 1 hour, decoction liquor and above-mentioned two kinds of filtrates merged, and filtered, and concentrated (40 ℃) to the relative density of filtrate decompression is 1.20 clear paste, adds above-mentioned Benexate Hydrochloride, incapsulates, promptly.
The preparation method of pill of the present invention: Herba Asari adds 6 times in water, and vapor distillation extracted 6 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 3 times of beta-schardinger dextrin-s, adds 2 times in water, grinds 30 minutes, and low temperature (50 ℃) drying is ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 75% alcohol reflux three times, and each 1.5 hours, filter, merging filtrate reclaims ethanol.6 flavors such as all the other Herba Epimedii add 10 times in water, decoct three times, each 1 hour, decoction liquor and above-mentioned two kinds of filtrates merge, and filter, and filtrate decompression concentrated (40 ℃) is 1.20 clear paste to relative density, add above-mentioned Benexate Hydrochloride, be ground into 100 orders, mix with 100 order amylum pregelatinisatums, it is standby to take out the 15-20% mixed powder; Standby powder adds 5～10% polyvinylpyrrolidone anhydrous alcohol solution mixings, and 20 orders, twice back of granulating forms the ball core, and last pot rolls, and look wet the situation powder that spreads pesticides and become ball, the drying that takes the dish out of the pot, screening, promptly.
The preparation method of granule of the present invention: Herba Asari adds 6 times in water, and vapor distillation extracted 6 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 3 times of beta-schardinger dextrin-s, adds 2 times in water, grinds 30 minutes, and low temperature (50 ℃) drying is ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 75% alcohol reflux three times, and each 1.5 hours, filter, merging filtrate reclaims ethanol.6 flavors such as all the other Herba Epimedii add 10 times in water, decoct each 1 hour three times, decoction liquor and above-mentioned two kinds of filtrates merge, filter, concentrated (40 ℃) to the relative density of filtrate decompression is 1.20 clear paste, adds above-mentioned Benexate Hydrochloride, amylum pregelatinisatum, sodium carboxymethyl cellulose, stevioside, mixing is crossed 80 mesh sieves, add suitable quantity of water and granulate 60 ℃ of drying under reduced pressure, granulate, packing, promptly.
The preparation method of soft capsule of the present invention: Herba Asari adds 6 times in water, and vapor distillation extracted 6 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 3 times of beta-schardinger dextrin-s, adds 2 times in water, grinds 30 minutes, and low temperature (50 ℃) drying is ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 75% alcohol reflux three times, and each 1.5 hours, filter, merging filtrate reclaims ethanol.6 flavors such as all the other Herba Epimedii add 10 times in water, decoct each 1 hour three times, decoction liquor and above-mentioned two kinds of filtrates merge, and filter, and filtrate decompression concentrated (40 ℃) is 1.20 clear paste to relative density, add above-mentioned Benexate Hydrochloride, pulverized 120～180 mesh sieve mixings.Gelatin, water and glycerol are melted heat preservation for standby use behind the glue, and medicated powder adds an amount of vegetable oil and stirs evenly, and colloid mill grinds to form even heavy-gravity pastel, the decompression degasification, and compacting, promptly.
The preparation method Herba Asari of tablet of the present invention adds 6 times in water, and vapor distillation extracted 6 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 3 times of beta-schardinger dextrin-s, adds 2 times in water, grinds 30 minutes, and low temperature (50 ℃) drying is ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 75% alcohol reflux three times, and each 1.5 hours, filter, merging filtrate reclaims ethanol.6 flavors such as all the other Herba Epimedii add 10 times in water, decoct three times, each 1 hour, decoction liquor and above-mentioned two kinds of filtrates merged, filter, concentrated (40 ℃) to the relative density of filtrate decompression is 1.20 clear paste, adds above-mentioned Benexate Hydrochloride, and it is an amount of to add starch, Pulvis Talci and magnesium stearate, granulate, compacting is in blocks, coating, promptly.
The preparation method of drop pill of the present invention: Herba Asari adds 6 times in water, and vapor distillation extracted 6 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 3 times of beta-schardinger dextrin-s, adds 2 times in water, grinds 30 minutes, and low temperature (50 ℃) drying is ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 75% alcohol reflux three times, and each 1.5 hours, filter, merging filtrate reclaims ethanol.6 flavors such as all the other Herba Epimedii add 10 times in water, decoct each 1 hour three times, decoction liquor and above-mentioned two kinds of filtrates merge, and filter, and filtrate decompression concentrated (40 ℃) is 1.20 clear paste to relative density, add above-mentioned Benexate Hydrochloride, pulverized 120 mesh sieves, join in 2: 1～4: 1 the molten polyethylene glycol 4000-polyethylene glycol 6000 of 3～5 times of amounts, stir, be transferred to the drop pill machine, drip and make ball, remove the dimethicone on surface, packing, promptly.
The preparation method of oral liquid of the present invention:, clean, concoct standby respectively with 7 flavor medical materials such as Radix Ginseng Rubra, Herba Epimedii, Fructus Psoraleae, Fructus Lycii, Herba Ephedrae, Radix Salviae Miltiorrhizae, Hirudo; Herba Asari adds 6 times in water, and vapor distillation extracted 6 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds Tween-80 makes its dissolving standby in right amount; Radix Ginseng Rubra is with 75% alcohol reflux three times, and each 1.5 hours, filter, merging filtrate reclaims ethanol, adds water to about 100ml, cold preservation 72 hours, filtration, filtrate for later use.6 flavors such as all the other Herba Epimedii add 10 times in water, decoct three times, and each 1 hour, decoction liquor and above-mentioned two kinds of filtrates merged, filter, it is 1.09 that filtrate decompression concentrates (40 ℃) to relative density, adds ethanol and makes and contain the alcohol amount and reach 70%, cold preservation, filter, filtrate recycling ethanol adds water to about 700ml, cold preservation 48 hours, filter, filtrate adds above-mentioned Radix Ginseng Rubra medicinal liquid and Herba Asari volatile oil, and it is an amount of to add refined honey, and steviosin is an amount of, regulating pH value is 7, adds water to 1000ml, stirs evenly, and filters, embedding, sterilization, promptly.
Foregoing invention oral liquid method of quality control is as follows:
[character] this product is henna liquid, is equipped with microprecipitation for a long time; Feeble QI, little suffering of distinguishing the flavor of.
Ginsenoside Rb is got in [discriminating] (1)
1, Re, Rg
1Reference substance adds methanol and makes the mixed solution that every 1ml contains 2mg, in contrast product solution.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw need testing solution and each 2 μ l of above-mentioned reference substance solution under [assay] top, put respectively on same silica gel g thin-layer plate, (4: 8: 3: 4) placing the lower floor's solution that spends the night below 10 ℃ was developing solvent with chloroform-n-butyl alcohol-methanol-water, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, at 105 ℃ of baking approximate numbers minute.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(2) get this product 10ml, add strong ammonia solution and regulate pH value to 9～10, add chloroform 30ml, jolting is extracted, and divides and gets chloroform solution, and evaporate to dryness, residue add methanol 1m1 makes dissolving, as need testing solution.Other gets the ephedrine hydrochloride reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol-liquor ammoniae fortis (20: 5: 0.5) is developing solvent, launch, take out, dry, spray is with ninhydrin solution, about 5 minutes of 105 ℃ of bakings.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get this product 10ml, add chloroform 30ml, jolting is extracted, and divides and gets chloroform solution, and evaporate to dryness, residue add chloroform 1ml makes dissolving, as need testing solution.Other gets psoralen and isopsoralen reference substance, and chlorination is copied into the mixed solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with petroleum ether (60～90 ℃)-ethyl acetate-methanol (20: 15: 1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
(4) get this product 30ml, add ethyl acetate extraction 2 times, each 20ml merges ethyl acetate liquid, and evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution.Other gets the icariin reference substance, adds ethanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, (5: 3: 1: 1) be developing solvent, expansion was taken out with ethyl acetate-butanone-formic acid-water, dry, spray, is put under the ultra-violet lamp (365nm) and is inspected 100 ℃ of heating several minutes with 1% aluminum chloride alcoholic solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
(5) get this product 5ml, add hydrochloric acid and regulate pH value to 2, the jolting that adds diethyl ether is extracted 2 times, and each 10ml merges ether solution, volatilizes, and residue adds ethanol 2ml makes dissolving, as need testing solution.Other gets the protocatechualdehyde reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw each 2 μ 1 of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with benzene-ethyl acetate-formic acid (8: 5: 0.8) is developing solvent, launch, take out, dry, spray is with the mixed solution of 2% liquor ferri trichloridi-1% potassium ferricyanide solution (1: 1).In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
[inspection] pH value should be 5.0～7.0 (an appendix VII of Chinese Pharmacopoeia version in 2000 G).
Relative density should be not less than 1.08 (an appendix VII of Chinese Pharmacopoeia version in 2000 A).
Other should meet every regulation relevant under the mixture item (an appendix I of Chinese Pharmacopoeia version in 2000 J).
[assay] precision is measured this product 5ml, puts in the separatory funnel, and the jolting that adds diethyl ether is extracted 3 times, each 20ml merges ether solution, and water 5ml washing, discard ether solution, cleaning mixture and above-mentioned water liquid merge, with water saturated n-butanol extraction 5 times, and 20ml at every turn, merge n-butanol extracting liquid, evaporate to dryness, residue add water 2ml makes dissolving, passes through D
101Type macroporous adsorptive resins (the post upper end adds neutral alumina 0.5g, water 50ml prewashing for the about 0.9cm of internal diameter, long 15cm) with water 50ml eluting, discards water liquid; With 10% ethanol 60ml eluting, discard 10% ethanol elution, continue with 70% ethanol 50ml eluting, collect eluent, evaporate to dryness, residue add methanol makes dissolving in right amount, is transferred in the 2ml measuring bottle, and is diluted to scale, shakes up, as need testing solution.Other gets the ginsenoside Rg
1Reference substance is an amount of, and accurate the title decides, and adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw need testing solution 4 μ l, reference substance solution 2 μ l and 4 μ l, respectively the cross point in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, placing the lower floor's solution that spends the night below 10 ℃ with chloroform-methanol-water (13: 7: 2) is developing solvent, exhibition launches apart from 16cm, take out, dry, spray is with 5% ethanol solution of sulfuric acid, about 10 minutes of 100～105 ℃ of bakings, clear to the speckle colour developing, take out, on lamellae, cover onesize glass plate, use immobilization with adhesive tape on every side, scan wavelength according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography scanning): λ
s=540nm, λ
R=700nm measures test sample trap integrated value and contrast trap integrated value, calculates, promptly.
Every of this product contains Radix Ginseng Rubra with ginsenoside R
G1(C
42H
72O
14) meter, must not be less than 2.0mg.
[function with cure mainly] temperature compensation heart kidney, blood circulation promoting and blood stasis dispelling.Be used for yang deficiency slow pulse disease, disease is seen slow pulse, kank, cardiopalmus, uncomfortable in chest, cold syndrome of the stomach cold extremities, soreness of the waist and knees, shortness of breath and fatigue or dizziness, dimly pale tongue or indentation is arranged or tongue with ecchymosis, petechia.Be equivalent to the deficiency of heart-YANG and kidney-YANG of light, moderate sinus bradycardia (heart rate＞50 time) and the slight supraventricular tachy-arrhythmia of sick sinus syndrome nonjoinder, the cold coagulation blood vessels are demonstrate,proved.
[usage and consumption] this product should be used under physician guidance.Oral, every 10ml, a 20ml, 2 times on the one, or follow the doctor's advice.
The present invention is on the Chinese medical theory basis, through a large amount of clinical practice screening gained.Its prescription is simple, onset is rapid, evident in efficacy, short treating period, be difficult for recurrence.In the selected medicine of the present invention, help arteries and veins with Radix Ginseng Rubra strongly invigorating primordial QI, QI invigorating, with Herba Epimedii warming YANG kidney tonifying, two medicines are monarch drug altogether, with Fructus Psoraleae, Fructus Lycii reinforcing the kidney and supporting YANG benefit essence is ministerial drug, is adjuvant drug with Herba Ephedrae, Herba Asari dispersing cold for relieving pain, is messenger drug with Radix Salviae Miltiorrhizae, Hirudo blood circulation promoting and blood stasis dispelling, eight medicines share, and play the effect of temperature compensation heart kidney, blood circulation promoting and blood stasis dispelling altogether.Be used for yang deficiency slow pulse card clinically, disease is seen slow pulse, kank, cardiopalmus, uncomfortable in chest, aversion to cold and cold limbs, soreness of the waist and knees, shortness of breath and fatigue or dizziness, dimly pale tongue or indentation is arranged or tongue with ecchymosis, petechia.Be equivalent to the deficiency of heart-YANG and kidney-YANG of light, moderate sinus bradycardia (rhythm of the heart＞50) and the slight supraventricular tachy-arrhythmia of sick sinus syndrome nonjoinder, the cold coagulation blood vessels are demonstrate,proved.In order to show the effect of medicine of the present invention to ARR treatments of type such as sick sinus syndrome and sinus bradycardias, the present invention has carried out following pharmacodynamic experiment.
Test the laboratory observation of 1 the present invention to the effect of the sick hole model of rabbit formaldehyde
1, method
Sick hole model is made: rabbit is with 3% pentobarbital sodium 45mg/kg, auricular vein injecting anesthetic.Separate trachea, connect artificial respirator.Open breast, open pericardium in the 4th intercostal, expose right atrium.With the little ring of homemade metal, the fixedly area of antrum interface 0.7 * 0.8cm.Soak 3～4 in 20% formaldehyde with diameter 0.8cm filter paper then, external application antrum interface 2～3 minutes.Index is that heart rate is reduced to and made 40%～50% before the film and knot property ease is rich.Treated behind the model stability 30 minutes, and measured every index.
Administration: model stability is after 30 minutes, and duodenum gives the oral liquid of the present invention and the heart treasured of variable concentrations respectively.The low dose of oral liquid of the present invention is 7.95g crude drug/kg (be equivalent to clinical consumption 5 times), middle 15.90g crude drug/kg (be equivalent to clinical consumption 10 times) and heavy dose of 23.85g crude drug/kg (be equivalent to clinical consumption 15 times).The dosage of heart treasured is 0.54g patent medicine/kg (be equivalent to clinical consumption 10 times).After administration 30,60 and 120min recorded heart rate (HR), sinoatrial conduction time (SACT), sinus node recovery time (SNRT).
2 result of the tests
2.1 heart rate (HR): the heart rate of making the preceding rabbit of film is 288～299 times/min.Heart rate drops to 156～168 times/min after making film.Duodenum gives oral liquid of the present invention (being respectively 5 times, 10 times, 15 times amounts of clinical consumption), after 30 minutes, 60 minutes, 120 minutes, heart rate makes all that (before the administration) raises behind the film, yet model group rabbit heart rate maintains the level of making behind the film always, no significant change the results are shown in Table 1.
Table 1 oral liquid duodenal administration of the present invention to the influence of tame rabbit hole model heart rate (
N=8)
| Dosage (g/kg) | Make HR before the film (inferior/min) | Make HR behind the film (inferior/min) | HR after the administration (inferior/min) | |||
| 30min | 60min | 120min | ||||
| The precious group of the heavy dose of group of the dosage group the present invention heart among model group small dose group the present invention of the present invention | - 7.95 15.9 23.85 0.54 | 296±15 288±18 298±19 299±15 295±16 | 161±7 168±11 156±11 158±9 160±8 | 162±5 172±9 177±10 ###**@189±7 ###***@@@168±8 # | 164±8 170±9 182±10 ###***@@189±7 ###***@@@170±8 ## | 163±7 169±10 177±8 ###***@@182±8 ###***@@@169±9 ## |
Annotate: after the administration with make film after (before the administration) compare ###P＜0.001, ##P＜0.01, #P＜0.05; The administration group is compared with model group, * * * P＜0.001, * * P＜0.01; Each group of oral liquid of the present invention is compared ， @@@P＜0.001 ， @@P＜0.01 ， @P＜0.05 with the precious group of the heart.
As shown in table 1, with make film after (before the administration) compare, give dosage among the present invention, heavy dose of group, 30min, 60min, 120min heart rate all obviously improve (P＜0.001) after the administration, and that the low dose group heart rate raises is not obvious, not statistically significant.60min, 120min heart rate also obviously improve (P＜0.01) after the administration of the precious group of the heart, and 30min also raises after the administration, and there is statistical significance P＜0.05.Each group of oral liquid of the present invention is compared with model group respectively with the precious group of the heart: 30min, 60min, 120min heart rate all obviously improve (P＜0.001, P＜0.05) than model group after each dosage group administration of oral liquid of the present invention.And the precious group of heart rising heart rate is not obvious, P＞0.05, not statistically significant.Each dosage group of oral liquid of the present invention is compared with heart treasured: wherein the heavy dose of group of the present invention is obvious than the precious rising heart rate of the heart, and there is remarkable statistical significance P＜0.001.Middle dosage group is compared with the precious group of the heart, the heart rate that also obviously raises, and P＜0.01, there is statistical significance P＜0.05.And small dose group is compared with heart treasured, and difference is not obvious, not statistically significant, P＞0.05.
2.2 SACT (SACT): the SACT of normal rabbits is 27～29ms.SACT extends to 65～70ms after making film.The large, medium and small dosage group of oral liquid of the present invention, SACT all obviously shortens (P＜0.001) behind administration 30min, 60min, 120min.And there is not significant change (P＞0.05) in the SACT of model group 2 hours after making film.The results are shown in Table 2.
Table 2 duodenal administration to the effect of tame rabbit hole model SACT (
N=8)
| Dosage (g/kg) | Make the preceding SACT (ms) of film | Make SACT (ms) behind the film | SACT after the administration (ms) | |||
| 30min | 60min | 120min | ||||
| The precious group of the heavy dose of group of the dosage group the present invention heart among model group small dose group the present invention of the present invention | - 7.95 15.90 23.85 0.54 | 27.2±2.0 28.5±3.0 29.0±3.0 27.8±2.5 28.0±2.7 | 65.4±5.4 66.4±6.3 67.0±8.0 70.0±5.4 68.2±6.1 | 64.5±6.3 45.2±5.3 ###***@@@43.3±7.5 ###***@@@43.1±2.6 ###***@@@55.3±6.7 ###** | 68.4±5.4 45.0±4.5 ###***@@@43.9±8.6 ###***@@44.0±3.7 ###***@@@57.3±4.4 ###*** | 61.9±4.5 42.4±6.3 ###*** 34.2±5.7 ###***@@ 35.4±4.2 ###***@@@ 45.5±3.3 ###*** |
Annotate: after the administration with make film after (before the administration) compare ###P＜0.001; The administration group is compared with model group, * * * P＜0.001, * * P＜0.01; Each group of oral liquid of the present invention is compared ， @@@P＜0.001 with the precious group of the heart.
As shown in table 2, with make film after (before the administration) compare, give oral liquid small dose group of the present invention, middle dosage group, heavy dose of group and the precious group of the heart, 30min, 60min, 120minSACT all obviously shorten (P＜0.001) after the administration.Oral liquid group of the present invention is compared with model group respectively with the precious group of the heart: 30min, 60min, 120minSACT all obviously shorten (P＜0.001, P＜0.05) after the administration of the precious group of each the dosage group of oral liquid of the present invention and the heart.Each dosage group of oral liquid of the present invention is compared with the precious group of the heart: except that small dose group 120min of the present invention shortens the not statistically significant than the precious SACT of the heart, all the other respectively organize all obvious than the precious SACT of shortening of the heart, and there is remarkable statistical significance P＜0.001.
2.3 corrected sinus node recovery time (CSNRT): make that the CSNRT of rabbit is 60～65ms before the film, extend to 113～125ms after making film.(P＜0.001)。Behind oral liquid duodenal administration of the present invention, CSRNT shortens, and continues more than 2 hours.Model group makes behind the film that CSNRT does not have significant change (P＞0.05) in 2 hours.The results are shown in Table 3.
Table 3 duodenum to the effect of tame rabbit hole MODEL C SNRT (
N=8)
| Dosage (g/kg) | Make the preceding CSNRT (ms) of film | Make CSNRT (ms) behind the film | CSNRT after the administration (ms) | |||
| 30min | 60min | 120min | ||||
| The precious group of the heavy dose of group of the dosage group the present invention heart among model group small dose group the present invention of the present invention | - 7.95 15.90 23.85 0.54 | 63.4±5.3 62.3±3.3 60.5±2.4 65.5±8.4 64.6±4.5 | 113.4±12.6 116.4±10.8 117.2±4.0 125.5±10.2 115.6±9.7 | 114.5±13.6 100.6±9.8 ###***89.2±7.4 ###***@@92.8±4.9 ###***@@98.7±6.8 ###*** | 112.1±15.9 73.5±7.7 ###**@@69.9±8.9 ###**@@75.0±6.7 ###**@@80.0±4.3 ###*** | 115.4±14.1 70.4±9.3 ###***@@@65.2±8.3 ###***@@72.8±13.8 ###***@@86.7±11 ###***6 |
Annotate: after the administration with make film after (before the administration) compare ###P＜0.001; Compare * * * P＜0.001, * * P＜0.01 after the administration with model group; Each group of oral liquid of the present invention is compared ， @@@P＜0.001 ， @@@P＜0.01 with the precious group of the heart.
As shown in table 3, with make film after (before the administration) compare, give oral liquid small dose group of the present invention, middle dosage group, heavy dose of group and the precious group of the heart, 30min, 60min, 120minCSNRT all obviously shorten (P＜0.001) after the administration.Compare with model group respectively with the precious group of the heart for of the present invention group: 30min, 60min, 120minCSNRT all obviously shorten (P＜0.001, P＜0.01) than model group after the administration of the precious group of each the dosage group of the present invention and the heart.Each dosage group of oral liquid of the present invention is compared with heart treasured: except that oral liquid small dose group 30min of the present invention shortens the not statistically significant than the precious CSNRT of the heart, all the other each groups are all obvious than the precious shortening of heart CSNRT, and (P＜0.001, P＜0.01) has remarkable statistical significance.
3, conclusion
This evidence, the large, medium and small dosage duodenal administration of oral liquid of the present invention can increase the heart rate of rabbit diseased sinus node model, and can improve the conduction of sinuatrial node.The heart rate that oral liquid of the present invention increases disease hole model rabbit reaches 20～30 times/min.Demonstrated the effect of the sick hole of good curing.Acting duration reached more than 2 hours, and the improvement of a lot of indexs all has significance to improve than the precious group of the positive control heart.
Test the laboratory observation of 2 oral liquids of the present invention to the effect of isolated rat heart work model
1, method
(open breast and take out heart, and (KHB contains 118mM NaCL, 11mM glucose 25mNaHCO to put into cold krebs-Hensleit (KHB) buffer by 65mg/kg, ip) anesthesia with pentobarbital sodium for rat
3, 4.7mMkcl, 1.2mM MgSO
4, 1.2mM KH
2PO
4, 2.5mM CaCL
2, 0.5mMNa-EDTA), preparation isolated heart, aortic cannulation.Hemodynamic index comprises: heart rate (HR, inferior/minute), coronary flow (CF, ml/min), aortic systolic pressure (SP, mmHg/min/ml) and arteria coronaria flow the arteries and veins diastolic pressure, (DP, mmHg), the oxygen saturation (C0) in coronary blood flow resistance (CVR, mmHg/min/ml) and the arteria coronaria effluent.Monitor 1 time every 5 minutes with controller.Behind heart perfusion 15 minutes, in 1 liter of KHB solution, add 1ml (2.25g crude drug) oral liquid of the present invention.Continue monitoring 30min after the dosing, observe the change of above-mentioned every index.And carry out statistics (T check) and handle.
2, result of the test
The result shows, with the KHB perfusion isolated heart 15 minutes that contains oral liquid of the present invention, the heart rate of heart model increases by 79 ± 4 times/minute (P＜0.001), and coronary flow increases by 7 ± 0.4ml/ minute (P＜0.001), and the coronary blood flow resistance reduces by 1.02 ± 0.34mmHg/mls
-1(P＜0.001).Oral liquid of the present invention is described except that having excited heart effect, expands the effect of coronary vasodilator in addition.But cardiac output and myocardial oxygen consumption there is not influence (P＞0.05).The results are shown in Table 4.
Table 4, oral liquid of the present invention to the influence of isolated rat perfused hearts hematodinamics index (
N=8)
| Before the administration | After the administration | The P value | |
| HR is (inferior/min) CF (ml/min) CO (ml/min) SP (mmHg) DP (mmHg) CVR (mmHg/mls -1) | 281±26 21.1±3.6 64.9±5.7 135±9 75±6 3.67±0.75 | 360±27 28.1±3.4 66.7±4.3 122±5 74±7 2.65±0.37 | ＜0.0001 ＜0.0001 ＞0.05 ＜0.001 ＞0.05 ＜0.001 |
3, conclusion
This experimental result shows that oral liquid of the present invention has the obvious effect that improves hemodynamic index to the isolated rat heart work model, can improve heart rate, increases coronary flow and reduces coronary resistance.Relatively, statistical significance is arranged all before and after the administration.But the oxygen saturation zero difference illustrates that myocardial oxygen consumption does not increase.
Test the laboratory observation of 3 oral liquids of the present invention to the effect of rats in vitro platelet aggregation
1, method
Extracorporeal platelet aggregation laboratory method: heart extracting blood behind the rat etherization, the anticoagulant in 1: 9 of 3.8% sodium citrate, centrifugal preparation platelet rich plasma (PRP) and platelet poor plasma (PPP).With ADP is derivant, BS631 type platelet aggregation instrument write down respectively each Mus blank assemble peak and centrifugal after last clear liquid medicine to the influence of platelet aggregation degree.For eliminating the influence of medicinal liquid color, in the PPP color comparison tube, add corresponding medicinal liquid.Represent drug potency to assemble suppression ratio.
2, result of the test
P of Rats RP and oral liquid of the present invention are assembled with ultimate density 20umolADP induced platelet after 37 ℃ of temperature are bathed 5 minutes.The result shows that this medicine obviously suppresses platelet function, does not assemble the peak relatively with the blank of medicine with same animal PRP, and suppression ratio is 30.71～53.80%, and difference is very obvious.Experiment is with the reliability (table 5) of the inhibition platelet effect method of proof of ligustrazine.
The anticoagulant effect of table 5 oral liquid of the present invention (
N=8)
| Group | Concentration (the mg crude drug/ml) | Assemble suppression ratio (%) |
| Oral liquid ligustrazine of the present invention | 113.75 91.0 72.8 0.50 | 53.80±20.32 ***## 31.48±15.60 *** 30.71±11.30 *** 29.74±19.78 *** |
Annotate: compare with the blank group:
* *P＜0.001; Compare with ligustrazine: ##P＜0.01.
3 conclusions
The result shows that the platelet aggregation that oral liquid of the present invention brings out ADP has obvious inhibitory action, assembles the peak relatively with same animal blank, and suppression ratio is 30.71%～53.80%, and there is remarkable statistical significance P＜0.001.High dose group is compared with the positive control drug ligustrazine, oral liquid high dose group of the present invention: there is obvious statistical significance P＜0.01.
Test the laboratory observation of 4 oral liquids of the present invention to the effect of mouse ear vein laser-induced bolt model
1, method
Mice gastric infusion every day 1 time, 30 minutes blue bovine serum albumin of tail vein injection 2% ivens after (dosage is respectively 20,10,5 times of clinical consumption per day) last administration on the 7th, 0.2ml/10g body weight.The identical Mus ear vein of selection part after 5 minutes, caliber, flow velocity is with the laser irradiation of HN-T3 type laser instrument, and luminous point accurately falls to penetrating in blood vessel central authorities, and blood flow changes and the thrombosis process in the 1.2mw.01ympus of the partial power microscopically direct observation irradiation process.Recording start exposes to formation time that occurs the first bolt of white crescent shape on the blood vessel and the full bolt time that blood flow stops whole thromboembolisms.
2, result of the test
Irritate stomach every day and give mice oral liquid of the present invention 1 time, but the significant prolongation laser-induced bolt time after 7 days, anti thrombotic action strengthens with dosage and strengthens, and when dosage be 31.8g/kg when above, take off the bolt phenomenon in the visible laser irradiation process.Positive control drug heart treasured also has certain anti thrombotic action, but effect is not as oral liquid of the present invention.(table 6)
The effect of the anti-laser-induced bolt of table 6 oral liquid of the present invention (
N=8)
| Group | Dosage (the g crude drug/kg) | First bolt time min | Full bolt time min |
| The blank oral liquid heart of the present invention treasured | ---- 31.80 15.90 7.95 0.72 | 1.60±0.39 2.75±0.63 *** 2.45±0.50 *** 2.43±0.52 *** 3.20±1.51 ** | 5.72±0.57 11.86±3.65 ***# 10.03±3.34 *** 7.86±2.95 * 9.04±2.87 ** |
Annotate: oral liquid of the present invention and heart treasured compare with the blank group respectively,
*P＜0.05
*P＜0.01
* *It is good that P＜0.001, two medicine is all imitated than blank group; The oral liquid of the present invention and the heart are relatively precious: oral liquid of the present invention is excellent than the precious effect of the heart, and there is statistical significance #P＜0.05.
3, conclusion
Experimental result shows: oral liquid of the present invention has obvious anti thrombotic action, but significant prolongation just bolt, full bolt formation time.When heavy dose of in laser irradiation process visible white thrombus come off, show platelet can not secure adhesion in blood vessel.
Show by above-mentioned pharmacological experiment study, oral liquid of the present invention has the significant conduction that improves sinuatrial node, improve the effect of hemodynamic index, improve heart rate, increase coronary flow and reduce coronary resistance, but do not increase myocardial oxygen consumption, suppress the platelet aggregation merit that ADP brings out, antithrombotic, but significant prolongation effect such as bolt, full bolt formation time just.
The specific embodiment
Embodiment 1: Radix Ginseng Rubra 100g, Herba Epimedii 250g, Fructus Psoraleae 750g, Fructus Lycii 250g, Herba Ephedrae 250g, Radix Salviae Miltiorrhizae 375g, Hirudo 250g, Herba Asari 50g; Herba Asari adds 6 times in water, and vapor distillation extracted 6 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds Tween-80 makes its dissolving standby in right amount; Radix Ginseng Rubra is with 75% alcohol reflux three times, and 1.5 hours for the first time, all the other each 1 hour, filter, merging filtrate reclaims ethanol, adds water to about 100ml, cold preservation 72 hours, filtration, filtrate for later use.6 flavors such as all the other Herba Epimedii add 10 times in water, decoct each 1 hour three times, collecting decoction filters, and the filtrate after filtrate and the distillation merges, filter, it is 1.09 that filtrate decompression concentrates (40 ℃) to relative density, adds ethanol and makes and contain the alcohol amount and reach 70%, cold preservation filters filtrate recycling ethanol, add water to about 700ml, cold preservation 48 hours filters, filtrate adds above-mentioned Radix Ginseng Rubra medicinal liquid and Herba Asari volatile oil, it is an amount of to add refined honey, and steviosin is an amount of, and regulating pH value is 7, add water to 1000ml, stir evenly, filter embedding, sterilization, promptly.
Embodiment 2:
Radix Ginseng Rubra 50g, Herba Epimedii 375g, Fructus Psoraleae 375g, Fructus Lycii 375g, Herba Ephedrae 125g, Radix Salviae Miltiorrhizae 200g, Hirudo 375g, Herba Asari 25g; Herba Asari adds 5 times in water, and vapor distillation extracted 8 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 2 times of beta-schardinger dextrin-s, adds 3 times in water, grinds 30 minutes, and low temperature (40 ℃) drying is ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 55% alcohol reflux three times, and each 1 hour, filter, merging filtrate reclaims ethanol.All the other Herba Epimedii etc. 6 flavor adds 8 times in water, decocts three times, and each 1 hour, decoction liquor merged with above-mentioned two kinds of filtrates, filtration, filtrate decompression concentrated 30 ℃ to relative density be 1.20 clear paste, add above-mentioned Benexate Hydrochloride, incapsulate, promptly.
Embodiment 3:
With Radix Ginseng Rubra 150g, Herba Epimedii 125g, Fructus Psoraleae 1125g, Fructus Lycii 125g, Herba Ephedrae 375g, Radix Salviae Miltiorrhizae 550g, Hirudo 125g;
Herba Asari adds 10 times in water, and vapor distillation extracted 4 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 6 times of beta-schardinger dextrin-s, adds 1 times in water, grinds 30 minutes, and 60 ℃ of cold drying are ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 90% alcohol reflux three times, and each 2 hours, filter, merging filtrate reclaims ethanol; 6 flavors such as all the other Herba Epimedii add 12 times in water, decoct three times, each 2 hours, decoction liquor and above-mentioned two kinds of filtrates merge, and filter, and it is 1.10 clear paste that filtrate decompression is concentrated into 60 ℃ of relative densities, add above-mentioned Benexate Hydrochloride, be ground into 100 orders, mix with 100 order amylum pregelatinisatums, it is standby to take out the 15-20% mixed powder; Standby powder adds 5～10% polyvinylpyrrolidone anhydrous alcohol solution mixings, and 20 orders, twice back of granulating forms the ball core, and last pot rolls, and look wet the situation powder that spreads pesticides and become ball, the drying that takes the dish out of the pot, screening, promptly.
Embodiment 4:
Radix Ginseng Rubra 125g, Herba Epimedii 300g, Fructus Psoraleae 950g, Fructus Lycii 150g, Herba Ephedrae 300g, Radix Salviae Miltiorrhizae 300g, Hirudo 300g, Herba Asari 60g; Herba Asari adds 8 times in water, and vapor distillation extracted 6 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 4 times of beta-schardinger dextrin-s, adds 3 times in water, grinds 30 minutes, and low temperature (50 ℃) drying is ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 65% alcohol reflux three times, and each 1.5 hours, filter, merging filtrate reclaims ethanol.6 flavors such as all the other Herba Epimedii add 10 times in water, decoct each 2 hours three times, decoction liquor and above-mentioned two kinds of filtrates merge, filter, concentrated (40 ℃) to the relative density of filtrate decompression is 1.15 clear paste, adds above-mentioned Benexate Hydrochloride, amylum pregelatinisatum, sodium carboxymethyl cellulose, stevioside, mixing is crossed 80 mesh sieves, add suitable quantity of water and granulate 60 ℃ of drying under reduced pressure, granulate, packing, promptly.
Embodiment 5:
Radix Ginseng Rubra 75g, Herba Epimedii 150g, saline Fructus Psoraleae (processed) 400g, Fructus Lycii 300g, Herba Ephedrae 150g, Herba Asari 40g, Radix Salviae Miltiorrhizae 450g, Hirudo 150g; Herba Asari adds 7 times in water, and vapor distillation extracted 7 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 2 times of beta-schardinger dextrin-s, adds 1 times in water, grinds 30 minutes, and low temperature (55 ℃) drying is ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 75% alcohol reflux three times, and each 1.5 hours, filter, merging filtrate reclaims ethanol.6 flavors such as all the other Herba Epimedii add 11 times in water, decoct each 1.5 hours three times, decoction liquor and above-mentioned two kinds of filtrates merge, and filter, and filtrate decompression concentrated (40 ℃) is 1.18 clear paste to relative density, add above-mentioned Benexate Hydrochloride, pulverized 120～180 mesh sieve mixings.Gelatin, water and glycerol are melted heat preservation for standby use behind the glue, and medicated powder adds an amount of vegetable oil and stirs evenly, and colloid mill grinds to form even heavy-gravity pastel, the decompression degasification, and compacting, promptly.
Embodiment 6: Radix Ginseng Rubra 100g, Herba Epimedii 250g, saline Fructus Psoraleae (processed) 750g, Fructus Lycii 250g, Herba Ephedrae 250g, Herba Asari 50g, Radix Salviae Miltiorrhizae 375g, Hirudo 250g; Herba Asari adds 9 times in water, and vapor distillation extracted 4 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 5 times of beta-schardinger dextrin-s, adds 3 times in water, grinds 30 minutes, and low temperature (60 ℃) drying is ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 60% alcohol reflux three times, and each 1.5 hours, filter, merging filtrate reclaims ethanol.6 flavors such as all the other Herba Epimedii add 9 times in water, decoct three times, each 1 hour, decoction liquor and above-mentioned two kinds of filtrates merged, filter, concentrated (40 ℃) to the relative density of filtrate decompression is 1.10 clear paste, adds above-mentioned Benexate Hydrochloride, and it is an amount of to add starch, Pulvis Talci and magnesium stearate, granulate, compacting is in blocks, coating, promptly.
Embodiment 7: Radix Ginseng Rubra 50～150, Herba Epimedii 125～375, saline Fructus Psoraleae (processed) 375～1125, Fructus Lycii 125～375, Herba Ephedrae 1 25～375, Herba Asari 25～75, Radix Salviae Miltiorrhizae 200～550, Hirudo 125～375.
With Radix Ginseng Rubra 150g, Herba Epimedii 325g, Fructus Psoraleae 900g, Fructus Lycii 325g, Herba Ephedrae 328g, Radix Salviae Miltiorrhizae 500g, Hirudo 370g, Herba Asari 70g; Herba Asari adds 10 times in water, and vapor distillation extracted 6 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 3 times of beta-schardinger dextrin-s, adds 2 times in water, grinds 30 minutes, and low temperature (45 ℃) drying is ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 75% alcohol reflux three times, and each 1.5 hours, filter, merging filtrate reclaims ethanol.6 flavors such as all the other Herba Epimedii add 8 times in water, decoct each 2 hours three times, decoction liquor and above-mentioned two kinds of filtrates merge, and filter, and filtrate decompression concentrated (40 ℃) is 1.20 clear paste to relative density, add above-mentioned Benexate Hydrochloride, pulverized 120 mesh sieves, join in 2: 1～4: 1 the molten polyethylene glycol 4000-polyethylene glycol 6000 of 3～5 times of amounts, stir, be transferred to the drop pill machine, drip and make ball, remove the dimethicone on surface, packing, promptly.
Claims (10)
1. treat ARR pharmaceutical composition for one kind, it is characterized in that according to the weight portion meter, the raw material of making this pharmaceutical composition active component is: Radix Ginseng Rubra 50～150, Herba Epimedii 125～375, saline Fructus Psoraleae (processed) 375～1125, Fructus Lycii 125～375, Herba Ephedrae 125～375, Herba Asari 25～75, Radix Salviae Miltiorrhizae 200～550, Hirudo 125～375.
2. the ARR pharmaceutical composition of treatment as claimed in claim 1, it is characterized in that according to the weight portion meter, making the said composition raw materials of effective components is: Radix Ginseng Rubra 75～125, Herba Epimedii 150～300, saline Fructus Psoraleae (processed) 400～950, Fructus Lycii 150～300, Herba Ephedrae 150～300, Herba Asari 40～60, Radix Salviae Miltiorrhizae 300～450, Hirudo 150～300.
3. the ARR pharmaceutical composition of treatment as claimed in claim 1 or 2 is characterized in that according to the weight portion meter, makes the said composition raw materials of effective components and is: Radix Ginseng Rubra 100, Herba Epimedii 250, saline Fructus Psoraleae (processed) 750, Fructus Lycii 250, Herba Ephedrae 250, Herba Asari 50, Radix Salviae Miltiorrhizae 375, Hirudo 250.
4. as claim 1, the ARR pharmaceutical composition of 2 or 3 described treatments, it is characterized in that described pharmaceutical composition is pill, granule, hard capsule, soft capsule, tablet, drop pill or oral liquid.
5. the ARR pharmaceutical composition of treatment as claimed in claim 4 is characterized in that described pharmaceutical composition is an oral liquid.
6. the ARR preparation of drug combination method of treatment as claimed in claim 4 is characterized in that: Herba Asari adds 5～10 times in water, and vapor distillation extracted 4～8 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 2～6 times of beta-schardinger dextrin-s, adds 1～3 times in water, grinds 30 minutes, and 40～60 ℃ of cold drying are ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 55%～90% alcohol reflux three times, and each 1～2 hour, filter, merging filtrate reclaims ethanol; 6 flavors such as all the other Herba Epimedii add 8～12 times in water, decoct three times, each 1～2 hour, decoction liquor and above-mentioned two kinds of filtrates merge, filter, it is 1.10～1.20 clear paste that filtrate decompression is concentrated into 30～60 ℃ of relative densities, adds above-mentioned Benexate Hydrochloride, mixing adds proper auxiliary materials again and makes different dosage form.
7. the ARR preparation of drug combination method of treatment as claimed in claim 6 is characterized in that: Herba Asari adds 6 times in water, and vapor distillation extracted 6 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds 3 times of beta-schardinger dextrin-s, adds 2 times in water, grinds 30 minutes, and 50 ℃ of cold drying are ground into fine powder, sieving for standby; Radix Ginseng Rubra is with 75% alcohol reflux three times, and each 1.5 hours, filter, merging filtrate reclaims ethanol; 6 flavors such as all the other Herba Epimedii add 10 times in water, decoct each 1 hour three times, decoction liquor and above-mentioned two kinds of filtrates merge, and filter, and it is 1.20 clear paste that filtrate decompression is concentrated into 40 ℃ of relative densities, add above-mentioned Benexate Hydrochloride, mixing adds proper auxiliary materials again and makes different dosage form.
8. the ARR preparation of drug combination method of treatment as claimed in claim 5 is characterized in that: Herba Asari adds 6 times in water, and vapor distillation extracted 6 hours, filters, and collects volatile oil, and filtrate device is in addition collected; Volatile oil adds Tween-80 makes its dissolving standby in right amount; Radix Ginseng Rubra is with 75% alcohol reflux three times, and 1.5 hours for the first time, all the other each 1 hour, filter, merging filtrate reclaims ethanol, adds water to about 100ml, cold preservation 72 hours, filtration, filtrate for later use; 6 flavors such as all the other Herba Epimedii add 10 times in water, decoct three times, and each 1 hour, collecting decoction, filter, the filtrate after filtrate and the distillation merges, and being concentrated into 40 ℃ of relative densities is 1.09, adds ethanol and makes and contain the alcohol amount and reach 70%, cold preservation filters, and filtrate recycling ethanol adds water to about 700ml, cold preservation 48 hours filters, and filtrate adds above-mentioned Radix Ginseng Rubra medicinal liquid and Herba Asari volatile oil, and it is an amount of to add refined honey, steviosin is an amount of, and regulating pH value is 7, adds water to 1000ml, stirs evenly, filter, embedding, sterilization, promptly.
9. claim 1, the application of 2 or 3 described Chinese medicine compositions in preparation treatment antiarrhythmic medicament.
10. the application of Chinese medicine composition as claimed in claim 8 in preparation treatment sick sinus syndrome and sinus bradycardia medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100191615A CN101181418B (en) | 2007-11-22 | 2007-11-22 | Medicine composition for curing arrhythmia and preparation method and detection method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100191615A CN101181418B (en) | 2007-11-22 | 2007-11-22 | Medicine composition for curing arrhythmia and preparation method and detection method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101181418A true CN101181418A (en) | 2008-05-21 |
| CN101181418B CN101181418B (en) | 2011-07-20 |
Family
ID=39446930
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007100191615A Active CN101181418B (en) | 2007-11-22 | 2007-11-22 | Medicine composition for curing arrhythmia and preparation method and detection method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101181418B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102048939A (en) * | 2010-12-30 | 2011-05-11 | 袁岳鹏 | Medicament for treating sinus bradycardia |
| CN103960568A (en) * | 2014-05-29 | 2014-08-06 | 延边长白山药业有限公司 | Ginseng total saponins chewable tablet and preparation method thereof |
| WO2019193400A1 (en) | 2018-04-06 | 2019-10-10 | Lietuvos sveikatos mokslų universitetas | Elsholtzia ciliata essential oil extract as antiarrhythmic drug |
| CN115266976A (en) * | 2022-07-25 | 2022-11-01 | 山东步长制药股份有限公司 | Ultra-high performance liquid phase detection method for Shenxian pulse-rising oral liquid |
| CN117838827A (en) * | 2024-03-08 | 2024-04-09 | 江西中医药大学附属医院 | Traditional Chinese medicine composition for treating chronic heart failure and preparation method thereof |
| CN117838827B (en) * | 2024-03-08 | 2024-05-31 | 江西中医药大学附属医院 | Traditional Chinese medicine composition for treating chronic heart failure and preparation method thereof |
-
2007
- 2007-11-22 CN CN2007100191615A patent/CN101181418B/en active Active
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102048939A (en) * | 2010-12-30 | 2011-05-11 | 袁岳鹏 | Medicament for treating sinus bradycardia |
| CN102048939B (en) * | 2010-12-30 | 2012-09-12 | 袁岳鹏 | Medicament for treating sinus bradycardia |
| CN103960568A (en) * | 2014-05-29 | 2014-08-06 | 延边长白山药业有限公司 | Ginseng total saponins chewable tablet and preparation method thereof |
| CN103960568B (en) * | 2014-05-29 | 2016-05-25 | 延边长白山药业有限公司 | A kind of general ginsenoside chewable tablets and preparation method thereof |
| WO2019193400A1 (en) | 2018-04-06 | 2019-10-10 | Lietuvos sveikatos mokslų universitetas | Elsholtzia ciliata essential oil extract as antiarrhythmic drug |
| US11654175B2 (en) | 2018-04-06 | 2023-05-23 | Lietuvos Sveikatos Mokslu Universitetas | Elsholtzia ciliata essential oil extract as antiarrhythmic drug |
| CN115266976A (en) * | 2022-07-25 | 2022-11-01 | 山东步长制药股份有限公司 | Ultra-high performance liquid phase detection method for Shenxian pulse-rising oral liquid |
| CN117838827A (en) * | 2024-03-08 | 2024-04-09 | 江西中医药大学附属医院 | Traditional Chinese medicine composition for treating chronic heart failure and preparation method thereof |
| CN117838827B (en) * | 2024-03-08 | 2024-05-31 | 江西中医药大学附属医院 | Traditional Chinese medicine composition for treating chronic heart failure and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101181418B (en) | 2011-07-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1899400B (en) | Detection method for injection containing ginseng and aconite root in raw material | |
| CN102908583B (en) | Traditional Chinese medicine composition for treating chest stuffiness and pains as well as preparation method, quality detection method and application of composition | |
| CN1931236B (en) | Medicine composition of red sage and rhodiola root | |
| CN101181418B (en) | Medicine composition for curing arrhythmia and preparation method and detection method thereof | |
| CN1923241B (en) | Medicine composition containing epimedium extract, uncaria extract, and gastrodine, and its preparation and use | |
| CN100418561C (en) | Chinese medicine composition and its prepn process and quality control method | |
| CN102000264B (en) | Detection method of composition for treating climacteric syndrome | |
| CN1887324B (en) | Chinese medicine composition for treating liver and kidney defect, and its preparation process and analysis method | |
| CN100534427C (en) | Ginkgo leaf extract and its preparation | |
| CN101152285B (en) | Pharmaceutical composition of snakegourd fruit and whitethorn leaf | |
| CN1931233B (en) | Medicine composition of red sage and epimedium for treating cardiac and cerebral vascular diseases | |
| CN102125662A (en) | Compound traditional Chinese medicine for treating apoplexia and preparation method and application thereof | |
| CN100563647C (en) | The Pharmaceutical composition of Herba Erigerontis and sodium tanshinon IIA silate injection | |
| CN103908571A (en) | Compound traditional Chinese medicine preparation for treating heart disease | |
| CN1923229B (en) | Pharmaceutical composition comprising notoginseng extract, Danshen extract and puerarin | |
| CN100563682C (en) | A kind of pharmaceutical composition of making by Folium Crataegi and Radix Rhodiolae and preparation method thereof | |
| CN1923228B (en) | Pharmaceutical composition comprising notoginseng extract, Danshen extract and ligustrazine | |
| CN101176751B (en) | Pharmaceutical composition of red sage root and cassia twig | |
| CN1294948C (en) | Medicine for boosting qi, strengthening spleen and nourishing liver and kidney and its preparation method | |
| CN100500171C (en) | Tranquilizing Chinese medicine composition and its preparing method and application | |
| CN101049356B (en) | Pharmaceutical composition of containing puerarin and leaves of hawthorn | |
| CN109893613A (en) | The Chinese native medicine compound prescription pellet and preparation method thereof of therapeutic radiation injury of lungs | |
| CN104510884A (en) | Compound traditional Chinese medicine preparation for treating cardiovascular and cerebrovascular diseases | |
| CN101108198B (en) | Epimedium erigeron pharmaceutical composition | |
| CN101190253B (en) | Medicinal composition containing mongolian snakegourd and notoginseng |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: SHANDONG BUCHANG PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: BUCHANG MEDICAL SCIENCE + TECHNOLOGY DEVELOPING CO., LTD., XIANYANG CITY Effective date: 20100108 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20100108 Address after: 369 Zhonghua Zhonghua Road, Heze City, Shandong Province, China: 274000 Applicant after: Shandong Buchang Pharmaceutical Co., Ltd. Address before: The postcode of Western Yuquanlu Road, Shaanxi, Xianyang Province, 712000 Applicant before: Buchang Medical & Drug Science & Tech. Development Co., Ltd., Xianyang |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 274000 No. 369 Zhonghua West Road, Heze City, Shandong Patentee after: Shandong Buchang Pharmaceuticals Co., Ltd. Address before: 274000 No. 369 Zhonghua West Road, Heze City, Shandong Patentee before: Shandong Buchang Pharmaceutical Co., Ltd. |