CN102475830A - Medicinal composition for treating coronary disease and angina pectoris, preparation method thereof and preparation thereof - Google Patents
Medicinal composition for treating coronary disease and angina pectoris, preparation method thereof and preparation thereof Download PDFInfo
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Abstract
The invention discloses a preparation method of a medicinal composition for treating the coronary disease and angina pectoris. The preparation method, which aims at disadvantages of present preparation methods of medicinal compositions for treating the coronary disease and angina pectoris allows an ultrasonic wave assisted extraction process to be applied on Cinnamomum migao, and makes the extraction time of Cinnamomum migao be reduced and the yield of Cinnamomum migao be improved. Ligusticum wallichii is heat-refluxed with ethanol, and the obtained extract goes through a macroporous adsorption resin column, so a large mount of impurities of tannins, proteins and the like in Ligusticum wallichii are effectively removed, thereby the purification and the refinement are sufficient, and the extraction is refined. Residue obtained after extracting volatile oil from Cinnamomum migao and residue of Ligusticum wallichii are decocted with water, so large polarity effective components of saccharides and the like are effectively extracted from the two medicines, thereby the medicine effect is increased. The medicinal composition for treating the coronary disease and angina pectoris, which is prepared with the extraction method in the invention, has the advantages of stable extraction technology, simple step, suitableness for the industrialized production, high contents of the effective components, and substantial curative effect. The invention also discloses the medicinal preparation and the preparation method of the medicinal composition for treating the coronary disease and angina pectoris.
Description
Technical field
The invention belongs to field of traditional Chinese medicine pharmacy, be specifically related to a kind of treatment treating coronary heart disease and angina pectoris compositions and its preparation method and preparation.
Background technology
Angina pectoris is to become the basis with functional change of coronary artery or organic diseases, acute, transience outbreak myocardial ischemia, anoxia and a kind of common clinical disease of causing.Coronary heart disease symptom shows as the pain that a kind of squeezing property takes place in thoracic cavity central authorities; And can delay to neck, chin, arm, back and stomach; Other of outbreak maybe symptoms have dizzy, tachypnea, perspire, shiver, feel sick and faint, and severe patient maybe be because heart failure and death.Angina pectoris serves as the clinical syndrome of main performance with ictal chest pain or chest discomfort, and its characteristics are paroxysmal shirtfront squeezing property pain perception, can be with other symptoms; Pain mainly is positioned at the breastbone rear portion, can be radiated to pareordia and left upper extremity, often betides work or when excited; Each outbreak 3～5min; But a few days is once, also can one day for several times, primary disease is more common in the male; Most patients are more than 40 years old, tired, excited, be satiated with food, catch cold, rainy weather, acute circulatory failure etc. are common inducement.
Development along with modern medicine; The treatment of angina pectoris obtains further standard; But the considerable part case is dissatisfied through doctor trained in Western medicine medical treatment effect; And interventional therapy, coronary artery bypass grafting (being also referred to as coronary artery bypass) etc. also have itself risk and limitation, all can not eliminate its original coronary artery pathological changes simultaneously, so Chinese medicine has its important value and potential advantages to the control of primary disease.Show from its clinical onset, belong to the category of China's Chinese medicine and pharmacy " thoracic obstruction ", " pained ".
The happy drop pill of the Cinnamomum Migao H.W.Li. heart is to utilize Guizhou Province Miao ethnic group medicine Cinnamomum Migao H.W.Li. that is usually used in treating obstruction of qi in the chest and cardialgia among the people to be monarch drug; According to Miao ethnic group's medication custom and theory of Chinese medical science reasonable formula, the pure Chinese medicinal preparation so that Cinnamoman Migao H.W.Li, Bulbus Allii Macrostemonis, Rhizoma Chuanxiong, Borneolum Syntheticum are formed has the effect of aromatic herbs activating YANG, regulating QI to relieve pain; Cure mainly by stagnation of YIN-cold, gas lose warm due to obstruction of qi in the chest and cardialgia (angina pectoris); That disease is seen is uncomfortable in chest, breathe hard, cardiopalmus, fear of cold, very then chest pain radiating to the back, the cold pain of sense very, hypopnea etc.The clinical prophylactic treatment type of stagnation of YIN-cold obstruction of qi in the chest and cardialgia that is used for obtains good result.
Cinnamomum Migao H.W.Li. has another name called Fructus cinnamomi camphorae, is the dry fruit of canella Cinnamomum Migao H.W.Li. migao H.W.Li, is distributed in provinces such as Yunnan, Guizhou, Guangxi.The Cinnamomum Migao H.W.Li. nature and flavor are sweet, hot, temperature, and the function warming spleen and stomach for dispelling cold, regulating QI to relieve pain is the Chinese herbal medicine of Guizhou minority nationality treatment obstruction of qi in the chest and cardialgia commonly used among the people.The pharmacological evaluation of system tentatively shows; The family that Cinnamoman Migao H.W.Li can resist due to high potassium and the NE exempts from the contraction of isolated aorta bar, and the rabbit isolated aorta is had tangible dilating effect, can improve myocardial ischemia; Reduce myocardial oxygen consumption; And bronchial smooth muscle, intestinal smooth muscle had extensive pharmacologically active, and toxicity is very low, is ideal source new drugs.
Rhizoma Chuanxiong Ligusticumchuanxiong Holt. is the dry rhizome of Umbelliferae Ligustrum plant Rhizoma Chuanxiong, records rhizome of chuanxiong in the Shennong's Herbal, classifies as top grade.Its former plant just has several since ancient times, and the different plant names in the place of production are different, so one of rhizome of chuanxiong is often titled with place name, and to show difference, medication at all times is a certified products with the Rhizoma Chuanxiong that originates in Sichuan.Rhizoma Chuanxiong has long medicinal history in China, and ancient Chinese medicine doctor is all as controlling headache, blood-activating and qi-promoting, the use of wind-expelling pain-stopping medicine; The modern disease that is mainly used in the treatment cardio-cerebrovascular clinically.Have blood-activating and qi-promoting, the function of wind-expelling pain-stopping is blood circulation promoting and blood stasis dispelling Chinese medicine commonly used.Contain lactone according to the bibliographical information Rhizoma Chuanxiong, alkaloids, phenols, and the multiple chemical compound of volatilization wet goods.
Bulbus Allii Macrostemonis is a traditional Chinese medicines simply, and the beginning is stated from Shennong's Herbal, is the dry bulb of Liliaceae allium Allium macrostemon AlliummacmstemonBge. or Chinese onion Allium chinensis G.Don.Nature and flavor are hot, bitter, warm, have warming middle-JIAO to activate yang, the chest stuffiness relieving of regulating the flow of vital energy, the effect of activating YANG and eliminating stagnation.The clinical thoracic obstruction, the chest pain radiating to the back etc. of being usually used in of Bulbus Allii Macrostemonis.Contain more than 10 kind of steroid saponins such as Bulbus Allii Macrostemonis glycoside A-I in the polar component of Bulbus Allii Macrostemonis, and nitrogen-containing compound such as adenosine, thymidine.Mainly be sulfur-containing compound in the volatile ingredient, wherein contain the methacrylic trithioether that platelet aggregation is had the strong inhibition effect.The element that also contains rich in amino acid and multiple needed by human body in addition in the Bulbus Allii Macrostemonis.
Borneolum Syntheticum is the processed goods of Dipterocarpaceae plant Borneolum Syntheticum resin, or the crystallization of extracting of feverfew Herba Blumeae Balsamiferae leaf, or is that raw material is through the synthetic highly finished product of chemical method with Oleum Terebinthinae, Camphora etc.The main component of borneol is dextro Borneolum Syntheticum (d.Borneol), and Blumeae preparatum Tabellae is mainly left-handed Borneolum Syntheticum (L.Borneol), and synthetic borneol still contains a large amount of isoborneol (Isoborneol).Borneolum Syntheticum is hot, bitter, is slightly cold.GUIXIN, spleen, lung meridian have the function of the refreshment of having one's ideas straightened out, clearing away heat to alleviate pain.Amplification on Canon of Materia Medica is summed up its effect characteristics and is " a little less than the gesture of walking alone then, assistant makes then meritorious ".Clinical usefulness controls that summer-heat is foul, having a dizzy spell due to the cholera eruptive disease, rush down tell remain unconscious, laryngopharynx swelling and pain, oral ulcer etc.In Chinese medicine, Borneolum Syntheticum Chang Zuowei " adjuvant ", " guiding drug " compatibility are used.See that from the modern pharmacology angle this effect possibly comprise that absorption, distribution, metabolism, drainage are relevant with the pharmacokinetics that influences other drug.Comprehensive multinomial discovering, Borneolum Syntheticum other drug is had promote to absorb, influence distributes, suppresses metabolic effect, helps reducing dosage, prolong drug action time, thus improve curative effect of medication.
Chinese patent CN03135734.2 publication number is that the patent document of CN1515303 discloses this kind preparation of drug combination method, and existing method for making is:
(1) Cinnamomum Migao H.W.Li. is extracted quintessence oil with steam distillation;
(2) Rhizoma Chuanxiong power is broken into coarse powder, and 95% ethanol reduced-pressure backflow with 10 times of amounts extracts secondary then, measures alcohol dipping 2 hours for 6 times for the first time; Reflux, extract, 3 hours is measured ethanol, reflux, extract, 2 hours for 4 times for the second time; Merge extracted twice liquid, the relative density of decompression recycling ethanol is 1.1, gets middle level liquid; It is about 1.2 to be evaporated to relative density, and using ammonia to transfer pH value is that three extractions, combining extraction liquid are divided with 6 times of chloroforms in 9 backs; Reclaim under reduced pressure chloroform and to be concentrated into relative density be 1.01-1.05 extracts Rhizoma Chuanxiong total alkaloids extractum;
(3) Bulbus Allii Macrostemonis is pulverized, and with 6 times of amount 95% alcohol dipping, reflux, extract, secondary, each 1 hour, being evaporated to relative density was 1.12-1.16, extracts Bulbus Allii Macrostemonis extractum;
With the Rhizoma Chuanxiong total alkaloids extractum that obtains, the mixing of Bulbus Allii Macrostemonis extractum, slight fever mix homogeneously, add in the fused polyvinylidene, mixing, adding Cinnamomum Migao H.W.Li. quintessence oil, Borneolum Syntheticum move in the drop pill liquid reservoir after mixing, and splash into liquid coolant, obtain drop pill.
In the above method for making, the monarch drug Cinnamomum Migao H.W.Li. only adopts steam distillation to extract volatile oil, length consuming time; Yield is low; Medicinal residues behind the extraction volatile oil are not fully utilized, and cause its contained other compositions such as polysaccharide to be wasted, and only adopt the method for alcohol extraction as the Rhizoma Chuanxiong of ministerial drug; Extracts active ingredients is insufficient, and the medical material utilization rate is low.So above-mentioned technology is perfect inadequately, do not provide the method for preparing of a cover entire effective, obtain the drug extract of high effective ingredient.How to improve the preparation extraction process of this treatment angina pectoris medicine; Make technology be beneficial to control, reducing production costs is suitable for industrialized great production, and the treatment angina pectoris effective ingredient content that obtains is high; Clinical effectiveness is good, is present urgent problem.
Summary of the invention
One of the object of the invention provides a kind of treatment treating coronary heart disease and angina pectoris compositions.
Another object of the present invention provides a kind of treatment treating coronary heart disease and angina pectoris preparation of compositions method.
Another object of the present invention provides a kind of treatment treating coronary heart disease and angina pectoris preparation and preparation method thereof.
The present invention is directed to the deficiency of existing treatment angina pectoris preparation of pharmaceutical compositions technology; Cinnamomum Migao H.W.Li. is adopted the ultrasonic-assisted extraction method, produce when utilizing ultrasonic vibration and transmit powerful energy, media structure is changed; Promote effective ingredient to get into this characteristic in the solvent; Compare with independent employing steam distillation, make the extraction time of Cinnamomum Migao H.W.Li. reduce, yield improves.After Rhizoma Chuanxiong adopts alcohol heating reflux; Extract passes through macroporous adsorptive resins again; Further the separate drug effective ingredient is effectively removed impurity such as tannins a large amount of in the medicine, protein, also can reduce the alkaloidal loss rate of effective ingredient in the medicine simultaneously; Purification refine is more abundant, extracts more concise.Cinnamomum Migao H.W.Li. is extracted the method that the medicinal residues of medicinal residues and Rhizoma Chuanxiong behind the volatile oil adopt decocting to boil, extract the big effective ingredient of saccharide isopolarity in the medical material effectively, the medicinal material extract rate improves, and practices thrift cost, increases drug effect.The treatment treating coronary heart disease and angina pectoris compositions that adopts method for distilling of the present invention to be prepared from, extraction process is stable, and step is simple, is fit to industrialized great production, and active constituent content is higher, and bioavailability is higher, and is evident in efficacy.
The present invention treats the treating coronary heart disease and angina pectoris compositions, according to listed as parts by weight, is prepared from following raw material medicaments:
350～600 parts of Cinnamomum Migao H.W.Li., 4～15 parts of Borneolum Syntheticums, 250～500 parts of Rhizoma Chuanxiongs, 25～50 parts of Bulbus Allii Macrostemonis.
Say accurately,, be prepared from following raw material medicaments according to listed as parts by weight:
450 parts of Cinnamomum Migao H.W.Li., 9 parts of Borneolum Syntheticums, 360 parts of Rhizoma Chuanxiongs, 36 parts of Bulbus Allii Macrostemonis.
Treatment treating coronary heart disease and angina pectoris preparation of compositions technology according to the invention is:
(1) take by weighing raw material, subsequent use;
(2) Cinnamomum Migao H.W.Li. is pulverized, and adds soak with ethanol, and ultrasonic echography extracts, sucking filtration, and the filtrate water vapor method steams solvent, obtains Cinnamoman Migao H.W.Li, and medicinal residues are subsequent use;
(3) Rhizoma Chuanxiong power is broken into coarse powder, extracts with alcohol heating reflux, reclaims ethanol, concentrates; After thick paste added the suitable quantity of water heating for dissolving, the reaction that sucking filtration, the macroporous adsorptive resins of filtrating, first water are eluted to sugar was negative; The reuse ethanol elution reclaims ethanol, concentrates, and filters; It is subsequent use to get total extract, collects medicinal residues, subsequent use;
(4) get the medicinal residues decocte with water of (2) and (3), extracting solution filters, and is condensed into thick paste;
(5) Bulbus Allii Macrostemonis is pulverized, and adds alcohol dipping, and heating and refluxing extraction merges, and reclaims ethanol, is condensed into extractum;
(6) extract, the thick paste of (4) and the extractum of (5) of merging (3), mix homogeneously, drying is pulverized, and adds the volatile oil and the Borneolum Syntheticum of (2) again, mixed.
Specifically, treatment treating coronary heart disease and angina pectoris preparation of compositions technology according to the invention is:
Step (2) Cinnamomum Migao H.W.Li. is ground into coarse powder, crosses 24 mesh sieves, adds 5～10 times of amount 75%～95% soak with ethanol, and soak time is: 5～10 hours; Ultrasonic extraction 60～90 minutes, sucking filtration is collected filtrating; Steam steams the solvent in the filtrating, obtains Cinnamoman Migao H.W.Li, and medicinal residues are subsequent use;
Step (3) Rhizoma Chuanxiong power is broken into coarse powder, crosses 24 mesh sieves, adds 5～15 times of amount 60～80% soak with ethanol 1～3 hour, reflux 3～4 times, and each extraction time is 2～5 hours; The 2nd time and after the amount of ethanol of number of times be 5～15 times of medical material weight, filter, merging filtrate, filtrating is concentrated into that relative density is 1.10～1.30 under 50～70 ℃ of conditions, adds ethanol and makes that to contain the alcohol amount be 50～80%; Left standstill 24～60 hours, and made deposition, merge, reclaim ethanol, be condensed into thick paste; It is 1-5: 5-1 that concentrated solution adds water to every milliliter of ratio with the every gram of medical material amount of volume, filters, and the reaction that the macroporous adsorptive resins of filtrating, first water are eluted to sugar is negative; Reuse 20～50% ethanol elutions are collected eluent, reclaim ethanol, concentrate; Filter, it is subsequent use to get extract, collects medicinal residues, subsequent use;
The medicinal residues that step (4) is got (2) and (3) add the water of 10～20 times of amounts, extract 3～4 times under 50～60 ℃ of conditions, and each 2～4 hours, merge extractive liquid, filtered, and merging filtrate is concentrated into relative density and is 1.10～1.25 extractum, and is subsequent use;
Step (5) Bulbus Allii Macrostemonis is pulverized, and crosses 24 mesh sieves, and it is 40～60% that adding 60～80% ethanol make pure content, places 36～60 hours; Make deposition, filter, get supernatant; Reclaim ethanol, and under 60～70 ℃ of conditions, to be concentrated into relative density be 1.10～1.30, be concentrated into thick paste;
More particularly, treatment treating coronary heart disease and angina pectoris preparation of compositions technology according to the invention is:
Step (2) Cinnamomum Migao H.W.Li. is ground into coarse powder, crosses 24 mesh sieves, adds 8 times of amount 75% soak with ethanol, and soak time is: 7 hours, and ultrasonic extraction 80 minutes, sucking filtration is collected filtrating, and steam steams the solvent in the filtrating, obtains Cinnamoman Migao H.W.Li, and medicinal residues are subsequent use;
Step (3) Rhizoma Chuanxiong power is broken into coarse powder, crosses 24 mesh sieves, adds 10 times of amount 70% soak with ethanol 2 hours, reflux 3 times, and each extraction time is 3 hours; The 2nd time and after the amount of ethanol of number of times be 8 times of medical material weight, filter, merging filtrate, filtrating is concentrated into that relative density is 1.15～1.25 under 50～70 ℃ of conditions, adds ethanol and makes that to contain the alcohol amount be 60%; Left standstill 48 hours, and made deposition, merge, reclaim ethanol, be condensed into thick paste; It is 1-5: 5-1 that concentrated solution adds water to every milliliter of ratio with the every gram of medical material amount of volume, filters, and the reaction that the macroporous adsorptive resins of filtrating, first water are eluted to sugar is negative; Reuse 35% ethanol elution is collected eluent, reclaims ethanol, concentrates; Filter, it is subsequent use to get extract, collects medicinal residues, subsequent use;
The medicinal residues that step (4) is got (2) and (3) add the water of 15 times of amounts, extract 3 times under 50～60 ℃ of conditions, and each 3 hours, merge extractive liquid, filtered, and merging filtrate is concentrated into relative density and is 1.10～1.25 extractum, and is subsequent use;
Step (5) Bulbus Allii Macrostemonis is pulverized, and crosses 24 mesh sieves, and adding 70% ethanol, to make pure content be 50%, placed 48 hours, makes deposition, filters, and gets supernatant, recovery ethanol, and under 60～70 ℃ of conditions, to be concentrated into relative density be 1.10～1.20, is concentrated into thick paste;
The composition and effectiveness that the present invention makes can adopt the conventional corresponding preparations method of knowing altogether, adds conventional adjuvant, like disintegrating agent, lubricant, binding agent etc., processes various oral formulations, comprises that drop pill, capsule, sheet, granule, soft capsule etc. are preferably drop pill.
The method for preparing that the present invention treats the treating coronary heart disease and angina pectoris preparation is on the basis of above-mentioned preparation treatment treating coronary heart disease and angina pectoris compositions, to add suitable adjuvant, is prepared into the preparation formulation that needs with conventional method.Drying wherein can get dry extract by drying under reduced pressure.
The preparation of drop pill: with the Rhizoma Chuanxiong total alkaloids extractum that makes in the above-mentioned treatment treating coronary heart disease and angina pectoris compositions, Bulbus Allii Macrostemonis extractum and medicinal residues extractum slight fever mix homogeneously; Drying and crushing; Add among the fused Polyethylene Glycol M6000; Mixing after adding Cinnamomum Migao H.W.Li. quintessence oil, Borneolum Syntheticum mix, is incubated subsequent use; As in the attemperator drop pill machine and keep substrate in stirring, start is instiled, and makes the coolant of drop pill molding of liquid paraffin or silicone oil with the fusion substrate of mix homogeneously.The drop pill of processing is taken out from coolant, carry out Rapid Cleaning with a small amount of dehydrated alcohol and be placed on forced air drying under 30～40 ℃ of conditions in the dish of stand, choose ball, glazing, packing.
Capsular preparation: with the Rhizoma Chuanxiong total alkaloids extractum that makes in the above-mentioned treatment treating coronary heart disease and angina pectoris compositions, Bulbus Allii Macrostemonis extractum and medicinal residues extractum slight fever mix homogeneously, drying under reduced pressure gets dry extract, and pulverizes, after adding Cinnamomum Migao H.W.Li. quintessence oil, Borneolum Syntheticum mix; Cross 100 mesh sieves, mixing is after 100 mesh sieves; Process soft material with 80% ethanol, cross 14 mesh sieves, granulate; Dry in about 60 ℃, granulate, encapsulated.
The preparation of tablet: with the Rhizoma Chuanxiong total alkaloids extractum that makes in the above-mentioned treatment treating coronary heart disease and angina pectoris compositions, Bulbus Allii Macrostemonis extractum and medicinal residues extractum slight fever mix homogeneously, drying under reduced pressure gets dry extract, and pulverizes, and adds Borneolum Syntheticum and stirs; Abundant mixing, drying is pulverized; The spray Cinnamoman Migao H.W.Li, mixing is granulated; With 16 mesh sieve granulate, the magnesium stearate that adds medicine extract 0.5-2% weight is a lubricant, adds the abundant mixing of microcrystalline Cellulose, amylum pregelatinisatum of medicine extract 5-20% weight; Be pressed into 1000, the bag film-coat promptly gets tablet.
Particulate preparation: with the Rhizoma Chuanxiong total alkaloids extractum that makes in the above-mentioned treatment treating coronary heart disease and angina pectoris compositions, Bulbus Allii Macrostemonis extractum and medicinal residues extractum slight fever mix homogeneously, drying under reduced pressure gets dry extract, and pulverizes; Adding Cinnamomum Migao H.W.Li. quintessence oil, Borneolum Syntheticum mix, and adding dextrin to total amount again is 1000g, pulverizes; Mixing is granulated drying; Granulate, packing.
Preparation of soft capsule: with the Rhizoma Chuanxiong total alkaloids extractum that makes in the above-mentioned treatment treating coronary heart disease and angina pectoris compositions, Bulbus Allii Macrostemonis extractum and medicinal residues extractum slight fever mix homogeneously, drying under reduced pressure gets dry extract, and pulverizes, and adding Cinnamomum Migao H.W.Li. quintessence oil, Borneolum Syntheticum stir abundant mixing; Granulate, granulate, the adding Cera Flava is an amount of, mixes; Mixture rolls wafer with automatic rotation and processes 1000, and drying is taken out; Use washing with alcohol, dry 48 hours, promptly get.
With the treatment treating coronary heart disease and angina pectoris composite preparation that the inventive method makes, through clinical verification, the result shows that pharmaceutical composition of the present invention is definite to treatment angina pectoris curative effect of disease; Safety is good, and quality controllability is high, and extraction process is stable; Step is simple, is fit to industrialized great production, and active constituent content is higher; Bioavailability is higher, and is evident in efficacy.
In order to make those of ordinary skills better understand the present invention, the applicant has carried out series of experiment research, to prove effect of the present invention:
One, pharmacodynamic study
The clinical observation test of experimental example 1 medicine composite for curing angina pectoris of the present invention
1.1 material:
1.1.1 medicine:
Preparation of the present invention: be prepared into drop pill (pressing embodiment 1 preparation), specification: every dress 25mg according to method for preparing of the present invention.
Contrast medicine: Radix Salviae Miltiorrhizae drop pill (Tianjin Tasly Pharmaceutical Co., Ltd's production), specification: every heavy 35mg.
1.1.2 subjects: Kunming mouse 18～20g, male and female half and half, the Wistar rat according to different experiments, has 80～100g, male and female half and half, purchases in the Guiyang Medical College Experimental Animal Center.
1.2 test method and result
1.2.1 test method
A, to the analgesic activity (hot plate method, writhing method) of mice
Get female Kunming mouse, by only putting into G-8402 type hot plate dolorimeter, measure and write down mice and metapedes required time (s) occurs licking as this Mus pain threshold, tie-in three times is averaged as pain threshold before this Mus normal value or the medicine.Select for use pain threshold to be divided into 3 groups at random with 30 of interior mices at 5s～30s; Dosage is: preparation 0.20g/kg of the present invention, and Radix Salviae Miltiorrhizae drop pill 0.20g/kg, the normal saline group gives the isometric(al) normal saline; Behind medicine 30,60,90min measures each Mus pain threshold; If mice is in the still i.e. taking-up of analgesia reaction of hot-plate instrument 60S, pain threshold is by 60s, and the result sees table 1.Other gets 30 of Kunming mouses, is divided into 3 groups at random by table 9 dosage.Each Mus lumbar injection 0.7% acetum 0.2ml/ of 1h only observes in the 15min and respectively organizes the writhing response number of times that mice is caused by acetic acid after the administration respectively, and the result sees table 1.
The happy drop pill of the table 1 Cinnamomum Migao H.W.Li. heart is to mice analgesic activity (hot plate method writhing method
n=10)
Annotate: compare with the normal saline group, experimental group P＜0.05, the treatment group is compared P＞0.05, there was no significant difference with matched group.
Above data show, show the happy drop pill group of the Cinnamomum Migao H.W.Li. heart, and the pain that thermostimulation and acetic acid chemical stimulation are caused all has analgesic activity, and action intensity is similar with Radix Salviae Miltiorrhizae drop pill.
Explanation has significant analgesia role according to the happy preparation of the Cinnamomum Migao H.W.Li. heart that the inventive method makes to mice.
B, the happy drop pill resisting oxygen lack of the Cinnamomum Migao H.W.Li. heart
With the normobaric hypoxia mice time-to-live be observation index, get 30 of Kunming mouses, male and female half and half; Body weight 20 ± 2g is divided into 3 groups at random, 10 every group; Dosage is: preparation 0.20g/kg of the present invention, and Radix Salviae Miltiorrhizae drop pill 0.20g/kg, the normal saline group gives the isometric(al) normal saline; Every day 1 time, continuous 3 times.1h behind the last medicine gets 10 mices for every group, by only putting into 250m] wide mouthed bottle airtight (bottle is put sodica calx 20g, and bottleneck is coated with vaseline), observe and respectively organize mouse diing time.(with respiratory arrest) is the time-to-live. get the remaining different third adrenal gland's rope 7.5mg/kg of a mice fortune lumbar injection that respectively organizes, behind the 30min, each group mice is put into wide mouthed bottle respectively with above-mentioned method.The result sees table 2.
The anti-anoxia in mice effect of the happy drop pill of the table 2 Cinnamomum Migao H.W.Li. heart (
n=10)
Annotate: compare with the normal saline group, experimental group P＜0.05, the treatment group is compared P＞0.05, there was no significant difference with matched group.
The result shows, compares with the normal saline group, and the happy drop pill of the Cinnamomum Migao H.W.Li. heart can prolong the anoxia in mice time-to-live, compares zero difference with the Radix Salviae Miltiorrhizae drop pill group.
Explanation has tangible reduction resisting oxygen lack according to the happy preparation of the Cinnamomum Migao H.W.Li. heart that the inventive method makes to mice.
Experimental example 2 safety testings
1 acute toxicity test: get healthy mice and carry out getting 40 white mice in addition after the trial test and carry out formal test, before the test with animal fasting 16 hours, not water restriction; Dosage is that 1000g (crude drug)/kg observed 7 days; Normal diet, drinking-water, observation index is the animal dead number.As a result, this concentration single administration (mice) was observed 7 days, none dead mouse.
2 successive administration toxicity tests: get 80 of healthy mices, be divided into 4 groups at random, investigational agent small dose group administration every day 1 time; Middle dose groups administration every day 3 times; Heavy dose of (adult's dosage 100 times) group administration every day 6 times; The blank group is given the N.S of equivalent; According to acute oral toxicity test, investigational agent is little, in, heavy dose of group dosage is 3mg/g, successive administration 14 days, normal diet drinking-water is observed continuously, matched group with.Observation index is the weight of animals growth pattern, active situation, diet situation, feces situation and death condition.As a result, each organizes mice does not all have the poisoning situation, and movable, diet drinking-water, feces situation are all normal, none death, and the body weight situation is carried out statistical procedures with the blank group, and the p value is all greater than 0.05, there was no significant difference.Result of the test is seen table 3.
Table 3 successive administration toxicity test result
Test Summary: test shows that preparation according to the invention is nontoxic.
Two, technical study
Experimental example 3 method for distilling are selected
A. the Cinnamomum Migao H.W.Li. quintessence oil extracts experiment
Get Cinnamomum Migao H.W.Li. 4500g, totally 4 parts, adopt method 1 (to add soak with ethanol respectively; Ultrasonic echography extracts, sucking filtration, the filtrate water vapor method steams solvent) and method 2 (using steam distillation separately) extraction Cinnamomum Migao H.W.Li. quintessence oil; Every kind of method is done 2 groups of parallel tests; Adopt the high resolution gas chromatography appearance that the content of two kinds of method gained eucalyptols is measured, investigate the extraction ratio of Cinnamomum Migao H.W.Li. eucalyptol in two kinds of methods, the result sees the following form 4.
Table 4 Cinnamomum Migao H.W.Li. essential oil content is measured the result
| Peak area | Content (%) |
| Method 1 | 291205 | 2.5 |
| Method 1 | 279557 | 2.4 |
| Method 2 | 221316 | 1.9 |
| Method 2 | 232964 | 2.0 |
Above data show that Cinnamomum Migao H.W.Li. adopts first soak with ethanol, and ultrasonic echography extracts, and it is higher that the steam method steams the content of eucalyptol in the quintessence oil that the method for solvent extracts again.
B. the extraction of Rhizoma Chuanxiong
Get Rhizoma Chuanxiong 3600g; Totally 3 parts, adopt respectively that water is carried, go up three kinds of methods of macroporous resin behind the ethanol extraction, alcohol extraction and extract, with the clarity of ferulaic acid content, solution in the Rhizoma Chuanxiong with to filter difficulty liquid be index; Investigate the extraction ratio of three kinds of methods, the result sees the following form 5.
Table 5 method for distilling is selected
| Ferulic acid % | Clarity | Filter difficulty or ease | |
| Water extract-alcohol precipitation | 13 | Clear and bright | Be prone to |
| Ethanol extraction | 15 | Clear and bright | Difficult |
| Cross macroporous resin after the alcohol extraction | 21 | Clear and bright | Be prone to |
Experimental result shows that three kinds of method extracting solution are all more transparent, and the method filtration of crossing macroporous resin after employing water extract-alcohol precipitation, the alcohol extraction is easier to, and the effective ingredient that wherein obtains with the method for crossing macroporous resin after the alcohol extraction is the highest, extracts more complete.So cross the method for distilling of macroporous resin after the preferred alcohol extraction.
C. the method for distilling of sugared content in the medicinal residues
Get the medicinal residues after the Cinnamomum Migao H.W.Li. quintessence oil extracts, totally 3 parts, employing water is carried, two kinds of methods of ethanol extraction, is index with the content of sugar in the total solid, the clarity and the filtration difficulty liquid of solution, investigates the extraction ratio of two kinds of methods, and the result sees the following form 6.
Table 6 method for distilling is selected
| Sugar % | Clarity | Filter difficulty or ease | |
| Water is carried | 15 | Clear and bright | Be prone to |
| Ethanol extraction | 13 | Clear and bright | Difficult |
Experimental result shows that two kinds of method extracting solution are all more transparent, and it is all more clear and bright to adopt water to carry with the method filtering solution of ethanol extraction, and it is part higher that water is carried the sugar that obtains, extract more complete, so the method that preferred water is carried.
Experimental example 4 stability experiments
With the happy drop pill content of the Cinnamomum Migao H.W.Li. heart that makes among the embodiment 1, preserve under the normal condition, respectively at 1 day, 3 days, 10 days, sampling in 30 days, with its character, the identification check of Cinnamomum Migao H.W.Li., Rhizoma Chuanxiong, the content of Fructus cinnamomi camphorae is for investigating index, and the result sees table 7.
Table 7 character and identification check result
The method of the assay of Cinnamomum Migao H.W.Li. is: precision takes by weighing drop pill content 0.5g, puts in the 20ml conical flask, adds water 10ml and 1,2-dichloromethane 20 micrograms, and sealing, 70 ℃ of balances 40 minutes are got 1.0ml head space gas sampling, repeat sample introduction 2 times, measure.Test sample and reference substance solution assay result see table 8
Table 8 Cinnamomum Migao H.W.Li. assay result
The experimental data of table 6 and table 7 shows that the happy better stability of preparation of the Cinnamomum Migao H.W.Li. heart that adopts the method for making among the embodiment 1 to make is easy to long-time preservation.
Below, enumerate embodiment the present invention is further described, but the present invention is not limited to following embodiment.
The specific embodiment:
Embodiment 1: the preparation of drop pill
Cinnamomum Migao H.W.Li. 450g, Borneolum Syntheticum 9g, Rhizoma Chuanxiong 360g, Bulbus Allii Macrostemonis 36g
Preparation technology is:
(1) Cinnamomum Migao H.W.Li. is ground into coarse powder, crosses 24 mesh sieves, adds 8 times of amount 75% soak with ethanol, and soak time is: 7 hours, and ultrasonic extraction 80 minutes, sucking filtration is collected filtrating, and steam steams the solvent in the filtrating, obtains Cinnamoman Migao H.W.Li, and medicinal residues are subsequent use;
(2) Rhizoma Chuanxiong power is broken into coarse powder, crosses 24 mesh sieves, adds 10 times of amount 70% soak with ethanol 2 hours, reflux 3 times, and each extraction time is 3 hours; The 2nd time and after the amount of ethanol of number of times be 8 times of medical material weight, filter, merging filtrate, filtrating is concentrated into that relative density is 1.15～1.25 under 50～70 ℃ of conditions, adds ethanol and makes that to contain the alcohol amount be 60%; Left standstill 48 hours, and made deposition, merge, reclaim ethanol, be condensed into thick paste; It is 1-5: 5-1 that concentrated solution adds water to every milliliter of ratio with the every gram of medical material amount of volume, filters, and the reaction that the macroporous adsorptive resins of filtrating, first water are eluted to sugar is negative; Reuse 35% ethanol elution is collected eluent, reclaims ethanol, concentrates; Filter, it is subsequent use to get extract, collects medicinal residues, subsequent use;
(3) medicinal residues of getting (1) and (2) add the water of 15 times of amounts, extract 3 times under 50～60 ℃ of conditions, and each 3 hours, merge extractive liquid, filtered, and merging filtrate is concentrated into relative density and is 1.10～1.25 extractum, and is subsequent use;
(4) Bulbus Allii Macrostemonis is pulverized, and crosses 24 mesh sieves, and adding 70% ethanol, to make pure content be 50%, placed 48 hours, makes deposition, filters, and gets supernatant, recovery ethanol, and under 60～70 ℃ of conditions, to be concentrated into relative density be 1.10～1.20, is concentrated into thick paste;
(5) extract, the extractum of (3) and the thick paste of (4) of merging (2), mix homogeneously, drying is pulverized, and adds the volatile oil and the Borneolum Syntheticum of (1) again, and mixing adds among the Polyethylene Glycol M6000 of molten condition, stirs, and it is uniformly dispersed, and is incubated subsequent use; As in the attemperator drop pill machine and keep substrate in stirring, start is instiled, and makes the coolant of drop pill molding of liquid paraffin or silicone oil with the fusion substrate of mix homogeneously.The drop pill of processing is taken out from coolant, carry out Rapid Cleaning with a small amount of dehydrated alcohol and be placed on forced air drying under 30～40 ℃ of conditions in the dish of stand, choose ball, glazing, packing.Promptly get 1000 of drop pills.
Usage and dosage: 3 times on the one, each 10.
Embodiment 2: the preparation of drop pill
Cinnamomum Migao H.W.Li. 550g, Borneolum Syntheticum 11g, Rhizoma Chuanxiong 440g, Bulbus Allii Macrostemonis 44g
Preparation technology is:
(1) Cinnamomum Migao H.W.Li. is ground into coarse powder, crosses 24 mesh sieves, adds 5 times of amount 95% soak with ethanol, and soak time is: 5 hours, and ultrasonic extraction 75 minutes, sucking filtration is collected filtrating, and steam steams the solvent in the filtrating, obtains Cinnamoman Migao H.W.Li, and medicinal residues are subsequent use;
(2) Rhizoma Chuanxiong power is broken into coarse powder, crosses 24 mesh sieves, adds 10 times of amount 80% soak with ethanol 3 hours, reflux 3 times, and each extraction time is 4 hours; The 2nd time and after the amount of ethanol of number of times be 10 times of medical material weight, filter, merging filtrate, filtrating is concentrated into that relative density is 1.15～1.30 under 50～70 ℃ of conditions, adds ethanol and makes that to contain the alcohol amount be 80%; Left standstill 60 hours, and made deposition, merge, reclaim ethanol, be condensed into thick paste; It is 1-3: 5-1 that concentrated solution adds water to every milliliter of ratio with the every gram of medical material amount of volume, filters, and the reaction that the macroporous adsorptive resins of filtrating, first water are eluted to sugar is negative; Reuse 40% ethanol elution is collected eluent, reclaims ethanol, concentrates; Filter, it is subsequent use to get extract, collects medicinal residues, subsequent use;
(3) medicinal residues of getting (1) and (2) add the water of 10 times of amounts, extract 4 times under 50～60 ℃ of conditions, and each 2 hours, merge extractive liquid, filtered, and merging filtrate is concentrated into relative density and is 1.10～1.25 extractum, and is subsequent use;
(4) Bulbus Allii Macrostemonis is pulverized, and crosses 24 mesh sieves, and adding 75% ethanol, to make pure content be 60%, placed 36 hours, makes deposition, filters, and gets supernatant, recovery ethanol, and under 60～70 ℃ of conditions, to be concentrated into relative density be 1.10～1.25, is concentrated into thick paste;
(5) extract, the extractum of (3) and the thick paste of (4) of merging (2), mix homogeneously, drying is pulverized, and adds the volatile oil and the Borneolum Syntheticum of (1) again, and mixing adds among the Polyethylene Glycol M6000 of molten condition, stirs, and it is uniformly dispersed, and is incubated subsequent use; As in the attemperator drop pill machine and keep substrate in stirring, start is instiled, and makes the coolant of drop pill molding of liquid paraffin or silicone oil with the fusion substrate of mix homogeneously.The drop pill of processing is taken out from coolant, carry out Rapid Cleaning with a small amount of dehydrated alcohol and be placed on forced air drying under 30～40 ℃ of conditions in the dish of stand, choose ball, glazing, packing.Promptly get 1000 of drop pills.
Usage and dosage: 3 times on the one, each 10.
Embodiment 3: the preparation of capsule
Cinnamomum Migao H.W.Li. 350g, Borneolum Syntheticum 7g, Rhizoma Chuanxiong 280g, Bulbus Allii Macrostemonis 28g
Preparation technology is:
(1) Cinnamomum Migao H.W.Li. is ground into coarse powder, crosses 24 mesh sieves, adds 5 times of amount 95% soak with ethanol, and soak time is: 5 hours, and ultrasonic extraction 90 minutes, sucking filtration is collected filtrating, and steam steams the solvent in the filtrating, obtains Cinnamoman Migao H.W.Li, and medicinal residues are subsequent use;
(2) Rhizoma Chuanxiong power is broken into coarse powder, crosses 24 mesh sieves, adds 5 times of amount 80% soak with ethanol 3 hours, reflux 4 times, and each extraction time is 2 hours; The 2nd time and after the amount of ethanol of number of times be 5 times of medical material weight, filter, merging filtrate, filtrating is concentrated into that relative density is 1.10～1.25 under 50～70 ℃ of conditions, adds ethanol and makes that to contain the alcohol amount be 50%; Left standstill 36 hours, and made deposition, merge, reclaim ethanol, be condensed into thick paste; It is 1-4: 4-1 that concentrated solution adds water to every milliliter of ratio with the every gram of medical material amount of volume, filters, and the reaction that the macroporous adsorptive resins of filtrating, first water are eluted to sugar is negative; Reuse 20% ethanol elution is collected eluent, reclaims ethanol, concentrates; Filter, it is subsequent use to get extract, collects medicinal residues, subsequent use;
(3) medicinal residues of getting (1) and (2) add the water of 10 times of amounts, extract 3 times under 50～60 ℃ of conditions, and each 4 hours, merge extractive liquid, filtered, and merging filtrate is concentrated into relative density and is 1.10～1.20 extractum, and is subsequent use;
(4) Bulbus Allii Macrostemonis is pulverized, and crosses 24 mesh sieves, and adding 60% ethanol, to make pure content be 40%, placed 60 hours, makes deposition, filters, and gets supernatant, recovery ethanol, and under 60～70 ℃ of conditions, to be concentrated into relative density be 1.10～1.20, is concentrated into thick paste;
(5) extract, the extractum of (3) and the thick paste of (4) of merging (2), mix homogeneously, drying is pulverized the slight fever mix homogeneously; Drying under reduced pressure gets dry extract, and pulverizes, and after adding Cinnamomum Migao H.W.Li. quintessence oil, Borneolum Syntheticum mix, crosses 100 mesh sieves; Mixing after 100 mesh sieves, is processed soft material with 80% ethanol, crosses 14 mesh sieves; Granulate, dry in about 60 ℃, granulate, encapsulated.
Usage and dosage: 3 times on the one, each 4.
Embodiment 4: the preparation of sheet
Cinnamomum Migao H.W.Li. 600g, Borneolum Syntheticum 12g, Rhizoma Chuanxiong 480g, Bulbus Allii Macrostemonis 48g
Preparation technology is:
(1) Cinnamomum Migao H.W.Li. is ground into coarse powder, crosses 24 mesh sieves, adds 10 times of amount 75% soak with ethanol, and soak time is: 10 hours, and ultrasonic extraction 90 minutes, sucking filtration is collected filtrating, and steam steams the solvent in the filtrating, obtains Cinnamoman Migao H.W.Li, and medicinal residues are subsequent use;
(2) Rhizoma Chuanxiong power is broken into coarse powder, crosses 24 mesh sieves, adds 15 times of amount 60% soak with ethanol 3 hours, reflux 4 times, and each extraction time is 5 hours; The 2nd time and after the amount of ethanol of number of times be 15 times of medical material weight, filter, merging filtrate, filtrating is concentrated into that relative density is 1.15～1.30 under 50～70 ℃ of conditions, adds ethanol and makes that to contain the alcohol amount be 80%; Left standstill 60 hours, and made deposition, merge, reclaim ethanol, be condensed into thick paste; It is 1-5: 5-1 that concentrated solution adds water to every milliliter of ratio with the every gram of medical material amount of volume, filters, and the reaction that the macroporous adsorptive resins of filtrating, first water are eluted to sugar is negative; Reuse 50% ethanol elution is collected eluent, reclaims ethanol, concentrates; Filter, it is subsequent use to get extract, collects medicinal residues, subsequent use;
(3) medicinal residues of getting (1) and (2) add the water of 20 times of amounts, extract 3 times under 50～60 ℃ of conditions, and each 2 hours, merge extractive liquid, filtered, and merging filtrate is concentrated into relative density and is 1.10～1.20 extractum, and is subsequent use;
(4) Bulbus Allii Macrostemonis is pulverized, and crosses 24 mesh sieves, and adding 70% ethanol, to make pure content be 50%, placed 36 hours, makes deposition, filters, and gets supernatant, recovery ethanol, and under 60～70 ℃ of conditions, to be concentrated into relative density be 1.10～1.20, is concentrated into thick paste;
(5) extract, the extractum of (3) and the thick paste slight fever mix homogeneously of (4) of merging (2), drying under reduced pressure gets dry extract, and pulverizes, and adds Borneolum Syntheticum and stirs; Abundant mixing, drying is pulverized, the spray Cinnamoman Migao H.W.Li; Mixing is granulated, and with 16 mesh sieve granulate, the magnesium stearate that adds medicine extract 0.5-2% weight is a lubricant; The abundant mixing of microcrystalline Cellulose, amylum pregelatinisatum that adds medicine extract 5-20% weight, tabletting, the bag film-coat promptly gets tablet.
Usage and dosage: 3 times on the one, each 4.
The preparation of embodiment 5 granules
Cinnamomum Migao H.W.Li. 400g, Borneolum Syntheticum 8g, Rhizoma Chuanxiong 320g, Bulbus Allii Macrostemonis 32g
(1) Cinnamomum Migao H.W.Li. is ground into coarse powder, crosses 24 mesh sieves, adds 7 times of amount 80% soak with ethanol, and soak time is: 8 hours, and ultrasonic extraction 80 minutes, sucking filtration is collected filtrating, and steam steams the solvent in the filtrating, obtains Cinnamoman Migao H.W.Li, and medicinal residues are subsequent use;
(2) Rhizoma Chuanxiong power is broken into coarse powder, crosses 24 mesh sieves, adds 8 times of amount 70% soak with ethanol 2 hours, reflux 4 times, and each extraction time is 3 hours; The 2nd time and after the amount of ethanol of number of times be 12 times of medical material weight, filter, merging filtrate, filtrating is concentrated into that relative density is 1.15～1.30 under 50～70 ℃ of conditions, adds ethanol and makes that to contain the alcohol amount be 60%; Left standstill 24 hours, and made deposition, merge, reclaim ethanol, be condensed into thick paste; It is 1-5: 5-1 that concentrated solution adds water to every milliliter of ratio with the every gram of medical material amount of volume, filters, and the reaction that the macroporous adsorptive resins of filtrating, first water are eluted to sugar is negative; Reuse 30% ethanol elution is collected eluent, reclaims ethanol, concentrates; Filter, it is subsequent use to get extract, collects medicinal residues, subsequent use;
(3) medicinal residues of getting (1) and (2) add the water of 15 times of amounts, extract 3 times under 50～60 ℃ of conditions, and each 3 hours, merge extractive liquid, filtered, and merging filtrate is concentrated into relative density and is 1.10～1.20 extractum, and is subsequent use;
(4) Bulbus Allii Macrostemonis is pulverized, and crosses 24 mesh sieves, and adding 65% ethanol, to make pure content be 55%, placed 48 hours, makes deposition, filters, and gets supernatant, recovery ethanol, and under 60～70 ℃ of conditions, to be concentrated into relative density be 1.10～1.25, is concentrated into thick paste;
(5) extract, the extractum of (3) and the thick paste of (4) of merging (2), the slight fever mix homogeneously, drying under reduced pressure gets dry extract, and pulverizes, and adding Cinnamomum Migao H.W.Li. quintessence oil, Borneolum Syntheticum mix, and adding dextrin to total amount again is 1000g, pulverizes, and mixing is granulated, drying, granulate is packed.
Usage and dosage: 3 times on the one, each 2 bags, boiled water is taken after mixing it with water.
Embodiment 6 preparation of soft capsule
Cinnamomum Migao H.W.Li. 500g, Borneolum Syntheticum 10g, Rhizoma Chuanxiong 400g, Bulbus Allii Macrostemonis 40g
Method for preparing is:
(1) Cinnamomum Migao H.W.Li. is ground into coarse powder, crosses 24 mesh sieves, adds 12 times of amount 85% soak with ethanol, and soak time is: 7 hours, and ultrasonic extraction 90 minutes, sucking filtration is collected filtrating, and steam steams the solvent in the filtrating, obtains Cinnamoman Migao H.W.Li, and medicinal residues are subsequent use;
(2) Rhizoma Chuanxiong power is broken into coarse powder, crosses 24 mesh sieves, adds 12 times of amount 65% soak with ethanol 3 hours, reflux 4 times, and each extraction time is 3 hours; The 2nd time and after the amount of ethanol of number of times be 10 times of medical material weight, filter, merging filtrate, filtrating is concentrated into that relative density is 1.15～1.25 under 50～70 ℃ of conditions, adds ethanol and makes that to contain the alcohol amount be 70%; Left standstill 48 hours, and made deposition, merge, reclaim ethanol, be condensed into thick paste; It is 1-5: 5-1 that concentrated solution adds water to every milliliter of ratio with the every gram of medical material amount of volume, filters, and the reaction that the macroporous adsorptive resins of filtrating, first water are eluted to sugar is negative; Reuse 35% ethanol elution is collected eluent, reclaims ethanol, concentrates; Filter, it is subsequent use to get extract, collects medicinal residues, subsequent use;
(3) medicinal residues of getting (1) and (2) add the water of 15 times of amounts, extract 3 times under 50～60 ℃ of conditions, and each 2 hours, merge extractive liquid, filtered, and merging filtrate is concentrated into relative density and is 1.10～1.20 extractum, and is subsequent use;
(4) Bulbus Allii Macrostemonis is pulverized, and crosses 24 mesh sieves, and adding 70% ethanol, to make pure content be 50%, placed 48 hours, makes deposition, filters, and gets supernatant, recovery ethanol, and under 60～70 ℃ of conditions, to be concentrated into relative density be 1.10～1.20, is concentrated into thick paste;
(5) extract, the extractum of (3) and the thick paste slight fever mix homogeneously of (4) of merging (2), drying under reduced pressure gets dry extract, and pulverizes, and adding Cinnamomum Migao H.W.Li. quintessence oil, Borneolum Syntheticum stir abundant mixing; Granulate, granulate, the adding Cera Flava is an amount of, mixes; Mixture rolls wafer with automatic rotation granulates, and drying is taken out; Use washing with alcohol, dry 48 hours, promptly get.
Usage and dosage: 3 times on the one, each 4.
Claims (10)
1. treat treating coronary heart disease and angina pectoris preparation of compositions method for one kind, it is made up of following step:
(1) take by weighing 350～600 parts of Cinnamomum Migao H.W.Li. by weight, 4～15 parts of Borneolum Syntheticums, 250～500 parts of Rhizoma Chuanxiongs, 25～50 parts of Bulbus Allii Macrostemonis, subsequent use;
(2) Cinnamomum Migao H.W.Li. is pulverized, and adds soak with ethanol, and ultrasonic echography extracts, sucking filtration, and the filtrate water vapor method steams solvent, obtains Cinnamoman Migao H.W.Li, and medicinal residues are subsequent use;
(3) Rhizoma Chuanxiong power is broken into coarse powder, extracts with alcohol heating reflux, reclaims ethanol, concentrates; After thick paste added the suitable quantity of water heating for dissolving, the reaction that sucking filtration, the macroporous adsorptive resins of filtrating, first water are eluted to sugar was negative; The reuse ethanol elution reclaims ethanol, concentrates, and filters; It is subsequent use to get total extract, collects medicinal residues, subsequent use;
(4) get the medicinal residues decocte with water of (2) and (3), extracting solution filters, and is condensed into thick paste;
(5) Bulbus Allii Macrostemonis is pulverized, and adds alcohol dipping, and heating and refluxing extraction merges, and reclaims ethanol, is condensed into extractum;
(6) extract, the thick paste of (4) and the extractum of (5) of merging (3), mix homogeneously, drying is pulverized, and adds the volatile oil and the Borneolum Syntheticum of (2) again, mixed.
2. according to the described preparation of drug combination method of claim 1, wherein the raw material of step (1) is: 450 parts of Cinnamomum Migao H.W.Li., 9 parts of Borneolum Syntheticums, 360 parts of Rhizoma Chuanxiongs, 36 parts of Bulbus Allii Macrostemonis.
3. according to claim 1 or 2 described preparation of drug combination methods, wherein:
Step (2) Cinnamomum Migao H.W.Li. is ground into coarse powder, crosses 24 mesh sieves, adds 5～10 times of amount 75%～95% soak with ethanol, and soak time is: 5～10 hours; Ultrasonic extraction 60～90 minutes, sucking filtration is collected filtrating; Steam steams the solvent in the filtrating, obtains Cinnamoman Migao H.W.Li, and medicinal residues are subsequent use;
Step (3) Rhizoma Chuanxiong power is broken into coarse powder, crosses 24 mesh sieves, adds 5～15 times of amount 60～80% soak with ethanol 1～3 hour, reflux 3～4 times, and each extraction time is 2～5 hours; The 2nd time and after the amount of ethanol of number of times be 5～15 times of medical material weight, filter, merging filtrate, filtrating is concentrated into that relative density is 1.10～1.30 under 50～70 ℃ of conditions, adds ethanol and makes that to contain the alcohol amount be 50～80%; Left standstill 24～60 hours, and made deposition, merge, reclaim ethanol, be condensed into thick paste; It is 1-5: 5-1 that concentrated solution adds water to every milliliter of ratio with the every gram of medical material amount of volume, filters, and the reaction that the macroporous adsorptive resins of filtrating, first water are eluted to sugar is negative; Reuse 20～50% ethanol elutions are collected eluent, reclaim ethanol, concentrate; Filter, it is subsequent use to get extract, collects medicinal residues, subsequent use;
The medicinal residues that step (4) is got (2) and (3) add the water of 10～20 times of amounts, extract 3～4 times under 50～60 ℃ of conditions, and each 2～4 hours, merge extractive liquid, filtered, and merging filtrate is concentrated into relative density and is 1.10～1.25 extractum, and is subsequent use;
Step (5) Bulbus Allii Macrostemonis is pulverized, and crosses 24 mesh sieves, and it is 40～60% that adding 60～80% ethanol make pure content, places 36～60 hours; Make deposition, filter, get supernatant; Reclaim ethanol, and under 60～70 ℃ of conditions, to be concentrated into relative density be 1.10～1.30, be concentrated into thick paste.
4. according to the described preparation of drug combination method of claim 3, wherein:
Step (2) Cinnamomum Migao H.W.Li. is ground into coarse powder, crosses 24 mesh sieves, adds 8 times of amount 75% soak with ethanol, and soak time is: 7 hours, and ultrasonic extraction 80 minutes, sucking filtration is collected filtrating, and steam steams the solvent in the filtrating, obtains Cinnamoman Migao H.W.Li, and medicinal residues are subsequent use;
Step (3) Rhizoma Chuanxiong power is broken into coarse powder, crosses 24 mesh sieves, adds 10 times of amount 70% soak with ethanol 2 hours, reflux 3 times, and each extraction time is 3 hours; The 2nd time and after the amount of ethanol of number of times be 8 times of medical material weight, filter, merging filtrate, filtrating is concentrated into that relative density is 1.15～1.25 under 50～70 ℃ of conditions, adds ethanol and makes that to contain the alcohol amount be 60%; Left standstill 48 hours, and made deposition, merge, reclaim ethanol, be condensed into thick paste; It is 1-5: 5-1 that concentrated solution adds water to every milliliter of ratio with the every gram of medical material amount of volume, filters, and the reaction that the macroporous adsorptive resins of filtrating, first water are eluted to sugar is negative; Reuse 35% ethanol elution is collected eluent, reclaims ethanol, concentrates; Filter, it is subsequent use to get extract, collects medicinal residues, subsequent use;
The medicinal residues that step (4) is got (2) and (3) add the water of 15 times of amounts, extract 3 times under 50～60 ℃ of conditions, and each 3 hours, merge extractive liquid, filtered, and merging filtrate is concentrated into relative density and is 1.10～1.25 extractum, and is subsequent use;
Step (5) Bulbus Allii Macrostemonis is pulverized, and crosses 24 mesh sieves, and adding 70% ethanol, to make pure content be 50%, placed 48 hours, makes deposition, filters, and gets supernatant, recovery ethanol, and under 60～70 ℃ of conditions, to be concentrated into relative density be 1.10～1.20, is concentrated into thick paste.
5. the pharmaceutical composition of the treatment sexual impotence that makes according to the method for preparing of claim 3 or 4.
6. treat the treating coronary heart disease and angina pectoris preparation for one kind, it contains the oral formulations that the described pharmaceutical composition of claim 5 is made the composition and effectiveness of medicine.
7. according to the described pharmaceutical preparation of claim 6, it is drop pill, capsule, sheet, granule, soft capsule etc.
8. the method for preparing the described treatment treating coronary heart disease and angina pectoris of claim 6 preparation; It is characterized in that on the described step of claim 1-4 basis; The composition and effectiveness that makes can be adopted the conventional corresponding preparations method of knowing altogether; Add acceptable accessories then, process peroral dosage form.
9. the method for preparing the drop pill of the described treatment angina pectoris of claim 7; It is characterized in that on the described step of claim 1-4 basis, with the Rhizoma Chuanxiong total alkaloids extractum that makes, Bulbus Allii Macrostemonis extractum and medicinal residues extractum slight fever mix homogeneously, drying and crushing; Add among the fused Polyethylene Glycol M6000; Mixing after adding Cinnamomum Migao H.W.Li. quintessence oil, Borneolum Syntheticum mix, is incubated subsequent use; As in the attemperator drop pill machine and keep substrate in stirring, start is instiled, and makes the coolant of drop pill molding of liquid paraffin or silicone oil with the fusion substrate of mix homogeneously.The drop pill of processing is taken out from coolant, carry out Rapid Cleaning with a small amount of dehydrated alcohol and be placed on forced air drying under 30～40 ℃ of conditions in the dish of stand, choose ball, glazing, packing.
10. the method for the tablet of the described treatment angina pectoris of preparation claim 7 is characterized in that on the described step of claim 1-4 basis with the Rhizoma Chuanxiong total alkaloids extractum that makes, Bulbus Allii Macrostemonis extractum and medicinal residues extractum slight fever mix homogeneously, drying under reduced pressure gets dry extract; Pulverize, add Borneolum Syntheticum and stir, abundant mixing, drying; Pulverize, the spray Cinnamoman Migao H.W.Li, mixing is granulated; With 16 mesh sieve granulate, the magnesium stearate that adds medicine extract 0.5-2% weight is a lubricant, adds the abundant mixing of microcrystalline Cellulose, amylum pregelatinisatum of medicine extract 5-20% weight; Be pressed into 1000, the bag film-coat promptly gets tablet.
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| CN104547457A (en) * | 2013-10-29 | 2015-04-29 | 贵州益佰制药股份有限公司 | Sustained-release dropping pill capable of regulating flow of vital energy and activating blood and preparation method of sustained-release dropping pill |
| CN104587145A (en) * | 2013-10-30 | 2015-05-06 | 贵州益佰制药股份有限公司 | Application of qi regulating and blood activating preparation in preparation of drug for prevention and treatment of acute coronary syndrome |
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| CN112029008A (en) * | 2020-09-16 | 2020-12-04 | 天津中新药业集团股份有限公司中新制药厂 | Ligusticum wallichii crude polysaccharide with special molecular weight, extraction process from dregs of a decoction and application |
| CN114073740A (en) * | 2020-08-12 | 2022-02-22 | 贵州益佰制药股份有限公司 | Preparation method of dripping pills for regulating qi and activating blood circulation |
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| CN103768147A (en) * | 2012-10-24 | 2014-05-07 | 贵州益佰制药股份有限公司 | Application of heart and stomach pain relieving preparation in preparing drugs treating cerebrovascular and related diseases |
| CN104547457A (en) * | 2013-10-29 | 2015-04-29 | 贵州益佰制药股份有限公司 | Sustained-release dropping pill capable of regulating flow of vital energy and activating blood and preparation method of sustained-release dropping pill |
| CN104547457B (en) * | 2013-10-29 | 2017-12-12 | 贵州益佰制药股份有限公司 | A kind of vital energy regualting and blood circulation-promoting sustained-release dropping pill and preparation method thereof |
| CN104587145A (en) * | 2013-10-30 | 2015-05-06 | 贵州益佰制药股份有限公司 | Application of qi regulating and blood activating preparation in preparation of drug for prevention and treatment of acute coronary syndrome |
| CN107536938A (en) * | 2016-06-23 | 2018-01-05 | 贵州益佰制药股份有限公司 | A kind of vital energy regualting and blood circulation-promoting preparation is preparing the application in treating or preventing renal damage medicine |
| CN107536938B (en) * | 2016-06-23 | 2020-12-18 | 贵州益佰制药股份有限公司 | Application of qi regulating and blood circulation promoting preparation in preparation of medicine for treating or preventing renal damage |
| CN114073740A (en) * | 2020-08-12 | 2022-02-22 | 贵州益佰制药股份有限公司 | Preparation method of dripping pills for regulating qi and activating blood circulation |
| CN114073740B (en) * | 2020-08-12 | 2022-11-15 | 贵州益佰制药股份有限公司 | Preparation method of dripping pills for regulating qi and activating blood circulation |
| CN112029008A (en) * | 2020-09-16 | 2020-12-04 | 天津中新药业集团股份有限公司中新制药厂 | Ligusticum wallichii crude polysaccharide with special molecular weight, extraction process from dregs of a decoction and application |
| CN112029008B (en) * | 2020-09-16 | 2022-11-08 | 天津中新药业集团股份有限公司中新制药厂 | Ligusticum wallichii crude polysaccharide with special molecular weight, extraction process from dregs of a decoction and application |
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