CN102475781A - Preparation method 3 of traditional Chinese medicine composition for treating primary hypertension - Google Patents
Preparation method 3 of traditional Chinese medicine composition for treating primary hypertension Download PDFInfo
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Abstract
The invention relates to a preparation method of a traditional Chinese medicine composition for treating primary hypertension, wherein the composition is prepared by processing the following raw material medicines in parts by weight: 3-12 parts of wine-processed rhubarb, 7.5-30 parts of ginger-processed coptis root, 15-60 parts of cassia seed, 15-60 parts of uncaria, 15-60 parts of motherwort fruit, 22.5-90 parts of selfheal, 15-60 parts of earthworm and 3-12 parts of red yeast rice.
Description
Technical field
The present invention relates to a kind of field of medicaments, especially relate to a kind of Chinese medicine composition of treating essential hypertension and preparation method thereof.
Background technology
With the metabolism syndrome is the modern civilization disease of representative, closely related with some modern life style, custom etc.Be the high risk factor of type 2 diabetes mellitus and cardiovascular disease, early diagnosis and early intervention metabolism syndrome help the control of type 2 diabetes mellitus and cardiovascular disease.
The definition of metabolism syndrome is core with the central obesity, merges blood pressure, blood glucose, triglyceride rising and/or HDL-C and reduces.Wherein relevant central obesity is adopted waistline as diagnosis index.
Hypertension is that to increase with SAP be the clinical syndrome of main performance, is modal cardiovascular disease, can be divided into essential hypertension and secondary hypertension two big classes; Most hypertension pathogenies are not clear, are called essential hypertension, account for more than 95% of total hypertension; In the patient of less than 5%; Hypertension is a kind of clinical manifestation of some disease, and this is called secondary hypertension in the clear and definite and independently cause of disease.In hypertension prevention and control, exist " three-hypers ", " three is low " phenomenon, three-hypers is that hypertensive sickness rate is high, rate of increase is high, hazardness is high, hypertensive high harm is apoplexy in China, secondly is heart infarction, renal damage; Three low be that hypertensive awareness is low, treatment rate is low, control rate is low.Announced that generaI investigation showed in 04 year, hypertensive awareness is 30.3%, treatment rate 24.7%, control rate 6.1%.Explain that people are to hypertension and hypertensive recognizing dangers wretched insufficiency.
The essential hypertension Chinese patent medicine that antimetabolic syndrome in the market causes is few, and existing medicine belongs to a bit cures the symptoms, not the disease, and some uses expensive composition, and some is cut and interrupt using owing to uncertain therapeutic efficacy in application process.
The invention provides a kind of determined curative effect, safe ready, little, the cheap pure traditional Chinese compound medicine of side effect.
Summary of the invention
The object of the present invention is to provide a kind of Chinese medicine composition of treating essential hypertension.
Another object of the present invention is to provide the method for preparing of said Chinese medicine composition.
Compositions of the present invention, be processed into by the raw material of following weight parts:
Radix et Rhizoma Rhei (stir-fried with wine) 3-12 part prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice 7.5-30 part Semen Cassiae 15-60 part
Ramulus Uncariae Cum Uncis 15-60 part Fructus Leonuri 15-60 part Spica Prunellae 22.5-90 part
Pheretima 15-60 part Monas cuspurpureus Went 3-12 part
Compositions of the present invention, preferably be processed into by the raw material of following weight parts:
Radix et Rhizoma Rhei (stir-fried with wine) 5-7 part prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice 10-20 part Semen Cassiae 20-40 part
Ramulus Uncariae Cum Uncis 20-40 part Fructus Leonuri 20-40 part Spica Prunellae 40-50 part
Pheretima 20-40 part Monas cuspurpureus Went 5-7 part
Compositions of the present invention particularly preferably is by the raw material of following weight parts and is processed into:
30 parts of 15 parts of Semen Cassiaes of 6 parts of prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice of Radix et Rhizoma Rhei (stir-fried with wine)
45 parts of 30 parts of Spica Prunellaes of 30 parts of Fructus Leonuris of Ramulus Uncariae Cum Uncis
6 parts in 30 parts of Monas cuspurpureus Went of Pheretima
In more than forming, weight is calculated with crude drug, and part is a weight portion; If with the gram is unit, more than composition can be made into a pharmaceutical preparation 5-50 preparation unit, and said preparation unit refers to; The final drug preparation of processing, as process solid preparation 5-50 unit, oral liquid 5-50ml etc.
More than form the preparation that can be made into 1-6 taking dose, as as tablet, process 18, each taking dose can be the 3-18 sheet, can take 1-6 time altogether.As as granule, process 6 bags, take the 1-2 bag at every turn, can take 3-6 time altogether.
More than form to be by weight as proportioning; When producing, can increase or reduce according to corresponding proportion; Like large-scale production can be unit with the kilogram, or is unit with the ton, and small-scale production can be unit with the milligram also; Weight can increase or reduce, but the constant rate of the raw medicinal herbs weight proportion between each composition.
The ratio of above weight proportion obtains through science screening, for especial patient, and like serious symptom or light disease, fat or modest patient, the proportioning of the amount of can corresponding adjustment forming increases or reduces being no more than 300%, and drug effect is constant.
Single medicinal material, especially ministerial drug and adjuvant drug in more than forming also can be by the suitable Chinese medicine replacements with identical property of medicine, and its drug effect of the Chinese medicine preparation after the replacement is constant.
Chinese medicine composition of the present invention is to process through extraction or other modes through the raw material of Chinese medicine that above-mentioned prescription is formed, and processes pharmaceutically active substance; Subsequently; With this material is raw material, adds the medicine acceptable carrier when needing, and processes according to the routine techniques of galenic pharmacy.Said active substance can obtain through extracting raw material of Chinese medicine respectively; Also can obtain through the co-extracted raw material of Chinese medicine; Also can obtain through other modes; As: through pulverize, squeeze, calcine, grind, sieve, percolation, extraction, water are carried, alcohol extraction, ester are carried, methods such as ketone is carried, chromatography obtain, these active substances can be the material of extractum form, can be that dry extract also can be a fluid extract, process different concentration according to the different needs decision of preparation.
Pharmaceutically active substance in the Chinese medicine composition of the present invention, its shared percentage by weight in preparation can be 0.1-99.9%, all the other are the medicine acceptable carrier.Pharmaceutical composition of the present invention exists with unit dosage form, and said unit dosage form is meant the unit of preparation, as every of tablet, and capsular every capsules, every bottle of oral liquid, every bag of granule etc.
Chinese medicine composition of the present invention can be any pharmaceutically useful dosage form, and these dosage forms comprise: tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, ointment, plaster, cream, spray, drop, patch.Preparation of the present invention, peroral dosage form preferably, as: capsule, tablet, oral liquid, granule, pill, powder, sublimed preparation, unguentum etc.
Chinese medicine composition of the present invention, the preparation of its oral administration can contain excipient commonly used, such as binding agent, filler, diluent, tablet agent, lubricant, disintegrating agent, coloring agent, flavoring agent and wetting agent, can carry out coating to tablet in case of necessity.
The filler that is suitable for comprises cellulose, mannitol, lactose and other similar filler.Suitable disintegrating agent comprises starch, polyvinylpyrrolidone and starch derivatives, for example sodium starch glycollate.Suitable lubricant comprises, for example magnesium stearate.The acceptable wetting agent of appropriate drug comprises sodium lauryl sulphate.
Can fill through mixing, the method that tabletting etc. are commonly used prepares solid oral composition.Mix repeatedly active substance is distributed in those compositionss of a large amount of filleies of whole use.
The form of oral liquid for example can be aqueous or oily suspensions, solution, Emulsion, syrup or elixir, perhaps can be a kind of available water before use or other suitable composite dry products of carrier.This liquid preparation can contain conventional additive; Such as suspending agent; For example sorbitol, syrup, methylcellulose, gelatin, hydroxyethyl-cellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenation edible fat; Emulsifying agent, for example lecithin, anhydro sorbitol monooleate or arabic gum; Non-aqueous carrier (they can comprise edible oil), for example almond oil, fractionated coconut oil, such as oily ester, propylene glycol or the ethanol of the ester of glycerol; Antiseptic, for example para hydroxybenzene methyl ester or propyl p-hydroxybenzoate or sorbic acid, and if desired, can contain conventional flavouring agent or coloring agent.
For injection, the liquid unit dosage forms of preparation contains active substance of the present invention and sterile carrier.According to carrier and concentration, can this chemical compound be suspended or dissolving.The preparation of solution is normally through being dissolved in active substance in a kind of carrier filter-sterilized before it is packed into a kind of suitable bottle or ampoule, sealing then.For example a kind of local anesthetic of adjuvant, antiseptic and buffer agent also can be dissolved in this carrier.In order to improve its stability, can be after the bottle of packing into that this compositions is freezing, and under vacuum, water is removed.
Chinese medicine composition of the present invention; When being prepared into medicament, optionally add suitable medicine acceptable carrier; Said medicine acceptable carrier is selected from: mannitol, sorbitol, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, vitamin C, EDTA disodium, EDTA calcium sodium, the alkali-metal carbonate of monovalence, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid, aminoacid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, cellulose and derivant thereof, alginate, gelatin, polyvinylpyrrolidone, glycerol, soil temperature 80, agar, calcium carbonate, calcium bicarbonate, surfactant, Polyethylene Glycol, cyclodextrin, beta-schardinger dextrin-, phospholipid material, Kaolin, Pulvis Talci, calcium stearate, magnesium stearate etc.
Compositions of the present invention is confirmed usage and dosage according to patient's situation in use, but obeys every day three times, each 1-20 agent, as: 1-20 bag or grain or sheet.
The method for preparing of the preferred present composition is following:
Radix et Rhizoma Rhei (stir-fried with wine) and Semen Cassiae add 5-10 40-60% ethanol extraction 1-3h doubly, filter, and medicinal residues add 5-10 40-60% ethanol extraction 1-3h doubly; Filter, medicinal residues discard, merge extractive liquid; 60～65 ℃ of 2-6 times of volumes that are evaporated to medical material, the 10-20 of thin up to medical material times volume leaves standstill 12-24h; The centrifuging and taking supernatant, D101 purification (1-2 of medical material amount is doubly), last appearance; Washing (4-6 column volume), 70-90% ethanol elution (15-20 column volume), eluent is evaporated to dried for 60～65 ℃.
Prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice adds 5-10 50-80% ethanol extraction 1-3h doubly, filters, and medicinal residues add 5-10 50-800% ethanol extraction 1-3h doubly, filter; Medicinal residues discard, merge extractive liquid,, 60～65 ℃ of 2-4 times of volumes that are evaporated to medical material; After being cooled to room temperature, adding concentrated hydrochloric acid and regulate pH to 1-2,12-24h is left standstill in cold preservation; Filter, filtrating discards, and gets the deposition part and is drying to obtain.
Spica Prunellae adds 10-15 times of water logging bubble 0.5-1h, be heated to boiling after, extract 1-3h, filter; Medicinal residues add 10-15 times of decocting and boil 1-3h, filter, and medicinal residues discard, and extracted twice liquid is merged; After being cooled to room temperature, D101 purification (1-2 of medical material is doubly), last appearance; Washing (4-6 column volume), 70-90% ethanol elution (10-20 of medical material is doubly), eluent is evaporated to dried for 60～65 ℃.
Ramulus Uncariae Cum Uncis and Fructus Leonuri add 5-10 times of water logging bubble 0.5-1h, be heated to boiling after, extract 1-3h, filter; Medicinal residues add 5-10 times of decocting and boil 1-3h, filter, and medicinal residues discard, and extracted twice liquid is merged; After being cooled to room temperature, D101 purification (1-2 of medical material is doubly), last appearance; Washing (4-6 column volume), 70-90% ethanol elution (10-20 of medical material is doubly), eluent is evaporated to dried for 60～65 ℃.
Pheretima and Monas cuspurpureus Went add 5-10 times of water logging bubble 0.5-1h, be heated to boiling after, extract 1-3h, filter, medicinal residues add 5-10 times of decocting and boil 1-3h; Filter, medicinal residues discard, and extracted twice liquid is merged, and 60～65 ℃ are evaporated to D60=1.05-1.10, get concentrated solution; After being cooled to room temperature, add 70-95% ethanol precipitate with ethanol, the limit edged stirs, and contains pure 50-70% to supernatant; Leave standstill 12-24h, filter, deposition discards, and filtrates 60～65 ℃ to be evaporated to dried.
In the prescription ratio, with above-mentioned five kinds of dry powder blend.
The active substance that above technology obtains mixes with the medicine acceptable carrier, processes pharmaceutical preparations composition according to the galenic pharmacy routine techniques.
The most preferred method for preparing of the present invention in an embodiment.
Further specify the therapeutic effect of pharmaceutical composition of the present invention through following experiment.
This experiment is the animal drug efficacy study that carries out to the Chinese medicine compound agent, and the animal model of employing is the spontaneous hypertension rat model, and route of administration is an oral administration gavage, and main observation index is mean arterial pressure (MBP).
Mean arterial pressure (MBP)=cardiac output (CO) * total peripheral vascular resistance (PR).
Experimental section mainly comprises dose-effect, the aging research of four kinds of Chinese medicine preparation blood pressure lowering.
One, material and method
(1) experiment material
1, tried thing: comprise that (ZF-7 ZY-1), is provided by sky, Tianjin scholar's power academy Chinese medicine four kinds of Chinese medicine preparation for CT-1, CT-5.Positive drug adopts irbesartan, and (the irbesartan sheet, France produces, the packing of Hangzhou Sanofi-Aventis people's livelihood pharmaceutical Co. Ltd.Lot number of the repackaged products: 0906193. batch number: 1797. dates of manufacture: 2009.02).
2, laboratory animal: adopt spontaneous hypertension rat (SHR), matched group adopts capital of a country Wistar Kyoto rat (WKY).Available from Beijing Vital River Experimental Animals Technology Co., Ltd., the quality certification number: SCXK (capital) 2006-0009.
3, instrument: the non-invasive blood pressure appearance (CODA of U.S. Kent company
TM2).
(2) experimental technique
1. experiment is divided into groups: totally six groups: model group, positive drug group, A, B, C, four administration groups of D.Each group is the SHR rat, and every group of 6-8 only.
2. dosage design: each kind dosage all calculates according to the crude drug amount, obtains following dosage every day.
The design of table 1 dosage
| Group | Sample number into spectrum | Every day is to the crude drug amount | Every day is to the medicated powder amount | Administration every day | The administration volume |
| A | CT-1 | 39.68g/kg | 3.0g/kg | 2 times | 1ml/100g |
| B | CT-5 | 39.68g/kg | 3.6g/kg | 2 times | 1ml/100g |
| C | ZF-7 | 39.68g/kg | 2.0g/kg | 2 times | 1ml/100g |
| D | ZY-1 | 39.68g/kg | 2.8g/kg | 2 times | 1ml/100g |
| Positive group | Irbesartan | 15.5mg/ |
1 time | 1ml/100g | |
| Model group | Tap water | 1ml/100g |
3, timeliness experiment: animal is raised a week after arriving laboratory in advance, measures basic blood pressure (basic blood pressure need be measured 1-2 week, guarantees that animal has adapted to instrument, and the blood pressure that measures is a true value).According to the basic blood pressure random packet.Fasting after dividing into groups, gastric infusion, the animal blood pressure of 0h, 12h, 24h after the METHOD FOR CONTINUOUS DETERMINATION administration.After animal detects, begin to carry out the long term administration experiment next day.
4, long-term experiment scheme: animal begins long-term experiment next day after finishing single-dose experiment, every day gastric infusion, successive administration one month.Measure blood pressure weekly once during this time.And grasp the time, guarantee that animal measuring basically at the same time, avoid in the daytime the influence of self fluctuation of blood pressure.Because animal is more, guarantee that consistent (because twice administration every day, the animal that detects afternoon is just given medicine for the first time in the morning to the time point that detects behind every animals administer, draws back delivery time.The animal that detect the morning is given medicine for the first time again after having surveyed.Guarantee that animal does not pass through fierce struggle before tested).Administration stops administration after one month, in convalescent period, the fluctuation situation of blood pressure detects twice weekly after the observation drug withdrawal, continues 2-3 week (looking concrete blood pressure situation).
(3) observation index
1, MAIN OUTCOME MEASURES: blood pressure comprises systolic pressure, diastolic pressure, mean arterial pressure.
2, other: body weight, heart rate, blood biochemical.
Two, experimental result
1, timeliness experiment
According to experimental result, behind single-dose, the blood pressure of each administration group all has certain downward trend.But more all there is not significance to reduce with model group.Heart rate is not found significant change.The result sees table 2,3,4,5
Mean arterial pressure timeliness experiment behind table 2 single-dose.mean±SD
Annotate: and with model group constantly relatively:
* *: p＜0.001
The variation of mean arterial pressure behind Fig. 1 single-dose
The time-effect relationship table that the after-contraction of table 3 single-dose is pressed.mean±SD
Annotate: and with model group constantly relatively:
* *: p＜0.001
The variation that the after-contraction of Fig. 2 single-dose is pressed
The timeliness data of diastolic pressure behind table 4 single-dose.mean±SD
Annotate: and with model group constantly relatively:
* *: p＜0.001
The variation of heart rate behind table 5 single-dose.mean±SD
Annotate: and with model group constantly relatively:
* *: p＜0.001
2, the mean arterial pressure of long term administration experiment changes
According to experimental result, in successive administration one month, the mean arterial pressure that observes each administration group weekly all has certain fluctuation.Two week of administration, the back was to the mean arterial pressure and the model group of each medicine group more all have significance reduction (p＜0.05) all around.The result sees table 3.
Table 6 long term administration is to the influence of each treated animal mean arterial pressure.mean±SD
Annotate: and with model group constantly relatively:
*: p＜0.05;
*: p＜0.01;
* *: p＜0.001
The variation of a monthly average arterial pressure of Fig. 3 administration.
3, the systolic pressure of long term administration experiment changes
According to experimental result, in successive administration one month, the systolic pressure that observes each administration group weekly all has certain fluctuation.Two week of administration, the back was to the systolic pressure and the model group of each medicine group more all have significance reduction (p＜0.05) all around.The result sees table 4.
Table 7 long term administration is to the influence of each treated animal systolic pressure.mean±SD
Annotate: and with model group constantly relatively:
*: p＜0.05;
*: p＜0.01;
* *: p＜0.001
The variation that Fig. 4 administration after-contraction in month is pressed.
4, the diastolic pressure of long term administration experiment changes
According to experimental result, in successive administration one month, the diastolic pressure that observes each administration group weekly all has certain fluctuation.Two week of administration, the back was to the diastolic pressure and the model group of each medicine group more all have significance reduction (p＜0.05) all around.The result sees table 5.
Table 8 long term administration is to the influence of each treated animal diastolic pressure.mean±SD
Annotate: and with model group constantly relatively:
*: p＜0.05;
*: p＜0.01;
* *: p＜0.001
The variation of Fig. 5 administration diastolic pressure after month
5, the changes in heart rate of long term administration experiment
All within normal range, the result sees table 6. to the heart rate of each treated animal
The heart rate influence of table 9 long term administration blood pressure lowering experiment.mean±SD
Annotate: and with model group constantly relatively:
*: p＜0.05;
*: p＜0.01;
* *: p＜0.001
6, body weight change during the administration.
Each group of spontaneous hypertension rat, month body weight amount of increase of administration is not very big, increasess slowly.
Table 10 long term administration is to the influence of each treated animal body weight.mean±SD
Annotate: and with model group constantly relatively:
*: p＜0.05;
*: p＜0.01;
* *: p＜0.001
Month the weight of animals of Fig. 6 administration changes
7, administration is after one month, and the blood biochemical of animal changes.
After the administration one month, the blood glucose value of each treated animal does not have significant difference.Also do not have significant difference between each group of ALT, the ALT of CT-1 group has significant reduction (p＜0.05), belongs in the normal physiological scope.The detection of AST finds that the AST of positive drug group compares with model group, obviously increases (p＜0.05).The AST of CT-1, CT-5 group compares with model group, then significantly reduces (p＜0.05).The testing result of TP (total serum protein) shows, removes the ZY-1 group, and the total protein of other each groups is compared with model group, all has and descend significantly (p＜0.001).Sero-abluminous detection finds that each administration treated animal is compared with model group, and albumin is significantly decline (p＜0.01) all.
Lipids detection, administration one month, the triglyceride and the model of CT-1, CT-5 group more all have reduction (p＜0.01) very significantly.After the administration one month, the T-CHOL value and the model group of ZY-1 group significantly increase (p＜0.01).But all the other each administration groups and model group are relatively, and T-CHOL all reduces (p＜0.01) very significantly
The prompting medicine has certain regulating action to Proteometabolism and lipid metabolism.
Table 11 administration is after one month, and the blood biochemical of animal changes (mean ± SD).
Annotate: compare with model group:
*: p＜0.05;
*: p＜0.01;
* *: p＜0.001
Table 12 administration is after one month, and the blood biochemical of animal changes (mean ± SD).
Annotate: compare with model group:
*: p＜0.05;
*: p＜0.01;
* *: p＜0.001
8, convalescent period animal the blood pressure testing result
After the administration one month, through one week of drug withdrawal, positive drug is compared with model group with the systolic pressure of ZF-7 group, still has significance to reduce (p＜0.05), and reduction value＞20mmHg.
After two weeks of drug withdrawal, systolic pressure, diastolic pressure and the mean arterial pressure of positive drug, ZF-7 and ZY-1 group are compared with model group, still have significance to reduce (p＜0.05), but reduction value＜20mmHg do not have biological significance.
After three weeks of drug withdrawal, each administration group is compared with model group, and significant difference is not all arranged.
Table 13 administration is after one month, through one week of over recovery, the body weight blood pressure of animal (mean ± SD).
Annotate: compare with model group:
*: p＜0.05;
*: p＜0.01;
* *: p＜0.001
Table 14 administration is after one month, through two weeks of over recovery, the body weight blood pressure of animal (mean ± SD).
Annotate: compare with model group:
*: p＜0.05;
*: p＜0.01;
* *: p＜0.001
Table 15 administration is after one month, through three weeks of over recovery, the body weight blood pressure of animal (mean ± SD).
Annotate: compare with model group:
*: p＜0.05;
*: p＜0.01;
* *: p＜0.001
Compositions among cited all embodiment of the present invention has the essentially identical effect with embodiment 1-4.
Compositions of the present invention has function and cures mainly: dampness eliminating to alleviate water retention, suppressing the hyperactive liver and subsiding YANG.Be used to treat the diseases such as essential hypertension that metabolism syndrome causes.Composition stable property of the present invention is good, few side effects, long shelf-life, characteristics such as therapeutic effect is remarkable.Simultaneously, method for preparing of the present invention is simple, is fit to production, and extraction ratio is high; Composition prescription is a conventional Chinese medicine in this invention, avoids the use of rare Chinese medicine and animal drugs, has reduced production cost, benefits extensive patients, is fit to promote.
Description of drawings
The variation of mean arterial pressure behind Fig. 1 single-dose
The variation that the after-contraction of Fig. 2 single-dose is pressed
The variation of a monthly average arterial pressure of Fig. 3 administration.
The variation that Fig. 4 administration after-contraction in month is pressed.
The variation of Fig. 5 administration diastolic pressure after month
Month the weight of animals of Fig. 6 administration changes
The specific embodiment:
Through following specific embodiment only is to explain content of the present invention, is not the further qualification to protection domain of the present invention.
30 parts of 15 parts of Semen Cassiaes of 6 parts of prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice of Radix et Rhizoma Rhei (stir-fried with wine)
45 parts of 30 parts of Spica Prunellaes of 30 parts of Fructus Leonuris of Ramulus Uncariae Cum Uncis
6 parts in 30 parts of Monas cuspurpureus Went of Pheretima
The independent cold water soak of Ramulus Uncariae Cum Uncis (150mL/ prescription), all the other flavour of a drug add cold water soak 20min (700mL/ prescription), be heated to boiling after, slow fire boiling 20min.Medical material and decoction liquor and Ramulus Uncariae Cum Uncis and soak thereof merge, and after intense fire boiled, slow fire boiling 5min poured out medicinal liquid, and 60～65 ℃ are evaporated to dried.
Embodiment 2, pharmaceutical composition of the present invention (CT-5)
30 parts of 15 parts of Semen Cassiaes of 6 parts of prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice of Radix et Rhizoma Rhei (stir-fried with wine)
45 parts of 30 parts of Spica Prunellaes of 30 parts of Fructus Leonuris of Ramulus Uncariae Cum Uncis
6 parts in 30 parts of Monas cuspurpureus Went of Pheretima
Full side adds 8 times of water loggings bubble 0.5h, be heated to boiling after, extract 1h, filter, medicinal residues add 7 times of decoctings and boil 1h; Filter, medicinal residues discard, and extracted twice liquid is merged, and 60～65 ℃ are evaporated to D60=1.05-1.10, get concentrated solution; After being cooled to room temperature, add 95% ethanol precipitate with ethanol, the limit edged stirs, and contains alcohol 70% to supernatant; Leave standstill 12h, filter, deposition discards, and filtrates 60～65 ℃ to be evaporated to dried.
The active substance that above technology obtains mixes with the medicine acceptable carrier, processes according to the galenic pharmacy routine techniques.
Embodiment 3 pharmaceutical compositions of the present invention (ZY-1)
30 parts of 15 parts of Semen Cassiaes of 6 parts of prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice of Radix et Rhizoma Rhei (stir-fried with wine)
45 parts of 30 parts of Spica Prunellaes of 30 parts of Fructus Leonuris of Ramulus Uncariae Cum Uncis
6 parts in 30 parts of Monas cuspurpureus Went of Pheretima
Radix et Rhizoma Rhei (stir-fried with wine) adds 8 times 50% ethanol extraction 1h, filters, and medicinal residues add 8 times 50% ethanol extraction 1h, filters; Medicinal residues discard, merge extractive liquid,, 60～65 ℃ of 4 times of volumes that are evaporated to medical material, 15 times of volumes of thin up to medical material; Leave standstill 12h, centrifuging and taking supernatant, D101 purification (medical material amount 1.5 times), last appearance; Washing (5 column volumes), 80% ethanol elution (7 column volumes), eluent is evaporated to dried for 60～65 ℃.
Prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice adds 8 times 70% ethanol extraction 1h, filters, and medicinal residues add 8 times 70% ethanol extraction 1h, filters; Medicinal residues discard, merge extractive liquid,, 60～65 ℃ of 3 times of volumes that are evaporated to medical material; After being cooled to room temperature, adding concentrated hydrochloric acid and regulate pH to 1.5,12h is left standstill in cold preservation; Filter, filtrating discards, and gets the deposition part and is drying to obtain.
All the other flavour of a drug except that Radix et Rhizoma Rhei (stir-fried with wine) and prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice add 8 times of water loggings bubble 0.5h, be heated to boiling after, extract 1h, filter; Medicinal residues add 7 times of decoctings and boil 1h, filter, and medicinal residues discard, and extracted twice liquid is merged, and 60～65 ℃ are evaporated to D60=1.05-1.10; Concentrated solution, be cooled to room temperature after, add 95% ethanol precipitate with ethanol, the limit edged stirs, and contains alcohol 70% to supernatant; Leave standstill 12h, filter, deposition discards, and filtrates 60～65 ℃ to be evaporated to dried.
In the prescription ratio, with above-mentioned three kinds of dry powder blend.
Embodiment 4 pharmaceutical compositions of the present invention (ZF-7)
30 parts of 15 parts of Semen Cassiaes of 6 parts of prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice of Radix et Rhizoma Rhei (stir-fried with wine)
45 parts of 30 parts of Spica Prunellaes of 30 parts of Fructus Leonuris of Ramulus Uncariae Cum Uncis
6 parts in 30 parts of Monas cuspurpureus Went of Pheretima
Radix et Rhizoma Rhei (stir-fried with wine) and Semen Cassiae add 8 times 50% ethanol extraction 1h, filter, and medicinal residues add 8 times 50% ethanol extraction 1h, filter; Medicinal residues discard, merge extractive liquid,, 60～65 ℃ of 4 times of volumes that are evaporated to medical material, 15 times of volumes of thin up to medical material; Leave standstill 12h, centrifuging and taking supernatant, D101 purification (medical material amount 1.7 times), last appearance; Washing (5 column volumes), 80% ethanol elution (16 column volumes), eluent is evaporated to dried for 60～65 ℃.
Prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice adds 8 times 70% ethanol extraction 1h, filters, and medicinal residues add 8 times 70% ethanol extraction 1h, filters; Medicinal residues discard, merge extractive liquid,, 60～65 ℃ of 3 times of volumes that are evaporated to medical material; After being cooled to room temperature, adding concentrated hydrochloric acid and regulate pH to 1.5,12h is left standstill in cold preservation; Filter, filtrating discards, and gets the deposition part and is drying to obtain.
Spica Prunellae adds 13 times of water loggings bubble 0.5h, be heated to boiling after, extract 1h, filter; Medicinal residues add 13 times of decoctings and boil 1h, filter, and medicinal residues discard, and extracted twice liquid is merged; After being cooled to room temperature, D101 purification (medical material 1.5 times), last appearance; Washing (5 column volumes), 80% ethanol elution (medical material 15 times), eluent is evaporated to dried for 60～65 ℃.
Ramulus Uncariae Cum Uncis and Fructus Leonuri add 9 times of water loggings bubble 0.5h, be heated to boiling after, extract 1h, filter; Medicinal residues add 9 times of decoctings and boil 1h, filter, and medicinal residues discard, and extracted twice liquid is merged; After being cooled to room temperature, D101 purification (medical material 1.5 times), last appearance; Washing (5 column volumes), 80% ethanol elution (medical material 15 times), eluent is evaporated to dried for 60～65 ℃.
Pheretima and Monas cuspurpureus Went add 8 times of water loggings bubble 0.5h, be heated to boiling after, extract 1h, filter, medicinal residues add 7 times of decoctings and boil 1h; Filter, medicinal residues discard, and extracted twice liquid is merged, and 60～65 ℃ are evaporated to D60=1.05-1.10, get concentrated solution; After being cooled to room temperature, add 95% ethanol precipitate with ethanol, the limit edged stirs, and contains alcohol 70% to supernatant; Leave standstill 12h, filter, deposition discards, and filtrates 60～65 ℃ to be evaporated to dried.
In the prescription ratio, with above-mentioned five kinds of dry powder blend.
Or
Radix et Rhizoma Rhei (stir-fried with wine) and Semen Cassiae add 5 times 40% ethanol extraction 1h, filter, and medicinal residues add 5 times 40% ethanol extraction 1h, filter; Medicinal residues discard, merge extractive liquid,, 60～65 ℃ of 2 times of volumes that are evaporated to medical material, 10 times of volumes of thin up to medical material; Leave standstill 12h, centrifuging and taking supernatant, D101 purification (medical material amount 1 times), last appearance; Washing (4 column volumes), 70% ethanol elution (15 column volumes), eluent is evaporated to dried for 60～65 ℃.
Prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice adds 5 times 50% ethanol extraction 1h, filters, and medicinal residues add 5 times 50% ethanol extraction 1h, filters; Medicinal residues discard, merge extractive liquid,, 60～65 ℃ of 2 times of volumes that are evaporated to medical material; After being cooled to room temperature, adding concentrated hydrochloric acid and regulate pH to 1,12h is left standstill in cold preservation; Filter, filtrating discards, and gets the deposition part and is drying to obtain.
Spica Prunellae adds 10 times of water loggings bubble 0.5h, be heated to boiling after, extract 1h, filter; Medicinal residues add 10 times of decoctings and boil 1h, filter, and medicinal residues discard, and extracted twice liquid is merged; After being cooled to room temperature, D101 purification (medical material 1 times), last appearance; Washing (4 column volumes), 70% ethanol elution (medical material 10 times), eluent is evaporated to dried for 60～65 ℃.
Ramulus Uncariae Cum Uncis and Fructus Leonuri add 5 times of water loggings bubble 0.5h, be heated to boiling after, extract 1h, filter; Medicinal residues add 5 times of decoctings and boil 1h, filter, and medicinal residues discard, and extracted twice liquid is merged; After being cooled to room temperature, D101 purification (medical material 1 times), last appearance; Washing (4 column volumes), 70% ethanol elution (medical material 10 times), eluent is evaporated to dried for 60～65 ℃.
Pheretima and Monas cuspurpureus Went add 5 times of water loggings bubble 0.5h, be heated to boiling after, extract 1h, filter, medicinal residues add 5 times of decoctings and boil 1h; Filter, medicinal residues discard, and extracted twice liquid is merged, and 60～65 ℃ are evaporated to D60=1.05-1.10, get concentrated solution; After being cooled to room temperature, add 70% ethanol precipitate with ethanol, the limit edged stirs, and contains alcohol 50% to supernatant; Leave standstill 12h, filter, deposition discards, and filtrates 60～65 ℃ to be evaporated to dried.
In the prescription ratio, with above-mentioned five kinds of dry powder blend.
Or
Radix et Rhizoma Rhei (stir-fried with wine) and Semen Cassiae add 10 times 60% ethanol extraction 3h, filter, and medicinal residues add 10 times 60% ethanol extraction 3h, filter; Medicinal residues discard, merge extractive liquid,, 60～65 ℃ of 6 times of volumes that are evaporated to medical material, 20 times of volumes of thin up to medical material; Leave standstill 24h, centrifuging and taking supernatant, D101 purification (medical material amount 2 times), last appearance; Washing (6 column volumes), 70-90% ethanol elution (20 column volumes), eluent is evaporated to dried for 65 ℃.
Prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice adds 10 times 80% ethanol extraction 3h, filters, and medicinal residues add 10 times 80% ethanol extraction 3h, filters; Medicinal residues discard, merge extractive liquid,, 60～65 ℃ of 4 times of volumes that are evaporated to medical material; After being cooled to room temperature, adding concentrated hydrochloric acid and regulate pH to 2,24h is left standstill in cold preservation; Filter, filtrating discards, and gets the deposition part and is drying to obtain.
Spica Prunellae adds 15 times of water loggings bubble 1h, be heated to boiling after, extract 3h, filter; Medicinal residues add 15 times of decoctings and boil 3h, filter, and medicinal residues discard, and extracted twice liquid is merged; After being cooled to room temperature, D101 purification (medical material 2 times), last appearance; Washing (6 column volumes), 90% ethanol elution (medical material 20 times), eluent is evaporated to dried for 60～65 ℃.
Ramulus Uncariae Cum Uncis and Fructus Leonuri add 10 times of water loggings bubble 1h, be heated to boiling after, extract 3h, filter; Medicinal residues add 10 times of decoctings and boil 3h, filter, and medicinal residues discard, and extracted twice liquid is merged; After being cooled to room temperature, D101 purification (medical material 2 times), last appearance; Washing (6 column volumes), 90% ethanol elution (medical material 20 times), eluent is evaporated to dried for 60～65 ℃.
Pheretima and Monas cuspurpureus Went add 10 times of water loggings bubble 1h, be heated to boiling after, extract 3h, filter, medicinal residues add 10 times of decoctings and boil 3h; Filter, medicinal residues discard, and extracted twice liquid is merged, and 60～65 ℃ are evaporated to D60=1.05-1.10, get concentrated solution; After being cooled to room temperature, add 95% ethanol precipitate with ethanol, the limit edged stirs, and contains alcohol 70% to supernatant; Leave standstill 24h, filter, deposition discards, and filtrates 60～65 ℃ to be evaporated to dried.
In the prescription ratio, with above-mentioned five kinds of dry powder blend.
Get 100 parts of any pharmaceutically active substances of embodiment 1-5, add the dextrin of 1.5 times of amounts, 0.5% sucrose, 1.5% microcrystalline Cellulose is processed soft material with an amount of dissolve with ethanol, granulates, and 60 ℃ of forced air dryings are granulated, and granulate promptly gets granule.
Embodiment 6, drop pill
Get 100 parts of any pharmaceutically active substances of embodiment 1-5, add 1000 parts Polyethylene Glycol, mix homogeneously, fusion, last drop pill machine is processed drop pill.
Get 100 parts of any pharmaceutically active substances of embodiment 1-5, add 5% polyvinylpolypyrrolidone, 0.1% magnesium stearate, 50% microcrystalline Cellulose; Process soft material with an amount of alcoholic solution, granulate, 60 ℃ of forced air dryings are granulated; Granulate, compacting promptly gets oral cavity disintegration tablet in flakes.
Embodiment 8, injectable powder
Get 0.5 part of any pharmaceutically active substance of embodiment 1-5,4.5 parts of glucoses, 0.9 part in sodium thiosulfate and distilled water 1ml, behind the said components mix homogeneously, lyophilization, 500 of packing promptly get injectable powder.
Embodiment 9, capsule
Get 100 parts of any pharmaceutically active substances of embodiment 1-5, add equivalent starch, sucrose and magnesium stearate are granulated, and incapsulate, and promptly get capsule.
Get 100 parts of any pharmaceutically active substances of embodiment 1-5, with starch, sodium carboxymethyl cellulose, Pulvis Talci mix homogeneously are granulated, and tabletting promptly gets tablet.
Embodiment 11, oral liquid
Get 2 parts of any pharmaceutically active substances of embodiment 1-5, with 4 parts in syrup, be dissolved in the pure water of 100ml, homogenizing filters, through high-temperature short-time sterilization (135 ℃, 4s).Sterile filling, packing make oral liquid.
Embodiment 12, pharmaceutical composition of the present invention
15 parts of 7.5 parts of Semen Cassiaes of 3 parts of prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice of Radix et Rhizoma Rhei (stir-fried with wine)
22.5 parts of 15 parts of Spica Prunellaes of 15 parts of Fructus Leonuris of Ramulus Uncariae Cum Uncis
3 parts in 15 parts of Monas cuspurpureus Went of Pheretima
The independent cold water soak of Ramulus Uncariae Cum Uncis (150mL/ prescription), all the other flavour of a drug add cold water soak 20min (700mL/ prescription), be heated to boiling after, slow fire boiling 20min.Medical material and decoction liquor and Ramulus Uncariae Cum Uncis and soak thereof merge, and after intense fire boiled, slow fire boiling 5min poured out medicinal liquid, and 60～65 ℃ are evaporated to dried.
Embodiment 13, pharmaceutical composition of the present invention
60 parts of 30 parts of Semen Cassiaes of 12 parts of prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice of Radix et Rhizoma Rhei (stir-fried with wine)
90 parts of 60 parts of Spica Prunellaes of 60 parts of Fructus Leonuris of Ramulus Uncariae Cum Uncis
12 parts in 60 parts of Monas cuspurpureus Went of Pheretima
The independent cold water soak of Ramulus Uncariae Cum Uncis (150mL/ prescription), all the other flavour of a drug add cold water soak 20min (700mL/ prescription), be heated to boiling after, slow fire boiling 20min.Medical material and decoction liquor and Ramulus Uncariae Cum Uncis and soak thereof merge, and after intense fire boiled, slow fire boiling 5min poured out medicinal liquid, and 60～65 ℃ are evaporated to dried.
Embodiment 14, pharmaceutical composition of the present invention
20 parts of 10 parts of Semen Cassiaes of 5 parts of prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice of Radix et Rhizoma Rhei (stir-fried with wine)
40 parts of 20 parts of Spica Prunellaes of 20 parts of Fructus Leonuris of Ramulus Uncariae Cum Uncis
5 parts in 20 parts of Monas cuspurpureus Went of Pheretima
The independent cold water soak of Ramulus Uncariae Cum Uncis (150mL/ prescription), all the other flavour of a drug add cold water soak 20min (700mL/ prescription), be heated to boiling after, slow fire boiling 20min.Medical material and decoction liquor and Ramulus Uncariae Cum Uncis and soak thereof merge, and after intense fire boiled, slow fire boiling 5min poured out medicinal liquid, and 60～65 ℃ are evaporated to dried.
Embodiment 15, pharmaceutical composition of the present invention
40 parts of 20 parts of Semen Cassiaes of 7 parts of prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice of Radix et Rhizoma Rhei (stir-fried with wine)
50 parts of 40 parts of Spica Prunellaes of 40 parts of Fructus Leonuris of Ramulus Uncariae Cum Uncis
7 parts in 40 parts of Monas cuspurpureus Went of Pheretima
The independent cold water soak of Ramulus Uncariae Cum Uncis (150mL/ prescription), all the other flavour of a drug add cold water soak 20min (700mL/ prescription), be heated to boiling after, slow fire boiling 20min.Medical material and decoction liquor and Ramulus Uncariae Cum Uncis and soak thereof merge, and after intense fire boiled, slow fire boiling 5min poured out medicinal liquid, and 60～65 ℃ are evaporated to dried.
The active substance that above different process obtains mixes with the medicine acceptable carrier, processes pharmaceutical preparations composition according to the galenic pharmacy routine techniques; Group component in the foregoing description can enlarge or reduce in scale according to the production needs simultaneously.
Claims (7)
1. a preparation of drug combination method of treating essential hypertension is characterized in that, said compositions is processed into by following bulk drugs process:
Radix et Rhizoma Rhei (stir-fried with wine) 3-12 part prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice 7.5-30 part Semen Cassiae 15-60 part
Ramulus Uncariae Cum Uncis 15-60 part Fructus Leonuri 15-60 part Spica Prunellae 22.5-90 part
Pheretima 15-60 part Monas cuspurpureus Went 3-12 part,
Said method for preparing may further comprise the steps:
Radix et Rhizoma Rhei (stir-fried with wine) and Semen Cassiae add 5-10 40-60% ethanol extraction 1-3h doubly, filter, and medicinal residues add 5-10 40-60% ethanol extraction 1-3h doubly; Filter, medicinal residues discard, merge extractive liquid; 60～65 ℃ of 2-6 times of volumes that are evaporated to medical material, the 10-20 of thin up to medical material times volume leaves standstill 12-24h; The centrifuging and taking supernatant, D101 purification (1-2 of medical material amount is doubly), last appearance; Washing (4-6 column volume), 70-90% ethanol elution (15-20 column volume), eluent is evaporated to dried for 60～65 ℃;
Prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice adds 5-10 50-80% ethanol extraction 1-3h doubly, filters, and medicinal residues add 5-10 50-80% ethanol extraction 1-3h doubly, filter; Medicinal residues discard, merge extractive liquid,, 60～65 ℃ of 2-4 times of volumes that are evaporated to medical material; After being cooled to room temperature, adding concentrated hydrochloric acid and regulate pH to 1-2,12-24h is left standstill in cold preservation; Filter, filtrating discards, and gets the deposition part and is drying to obtain;
Spica Prunellae adds 10-15 times of water logging bubble 0.5-1h, be heated to boiling after, extract 1-3h, filter; Medicinal residues add 10-15 times of decocting and boil 1-3h, filter, and medicinal residues discard, and extracted twice liquid is merged; After being cooled to room temperature, D101 purification (1-2 of medical material is doubly), last appearance; Washing (4-6 column volume), 70-90% ethanol elution (10-20 of medical material is doubly), eluent is evaporated to dried for 60～65 ℃;
Ramulus Uncariae Cum Uncis and Fructus Leonuri add 5-10 times of water logging bubble 0.5-1h, be heated to boiling after, extract 1-3h, filter; Medicinal residues add 5-10 times of decocting and boil 1-3h, filter, and medicinal residues discard, and extracted twice liquid is merged; After being cooled to room temperature, D101 purification (1-2 of medical material is doubly), last appearance; Washing (4-6 column volume), 70-90% ethanol elution (10-20 of medical material is doubly), eluent is evaporated to dried for 60～65 ℃;
Pheretima and Monas cuspurpureus Went add 5-10 times of water logging bubble 0.5-1h, be heated to boiling after, extract 1-3h, filter, medicinal residues add 5-10 times of decocting and boil 1-3h; Filter, medicinal residues discard, and extracted twice liquid is merged, and 60～65 ℃ are evaporated to D60=1.05-1.10, get concentrated solution; After being cooled to room temperature, add 70-95% ethanol precipitate with ethanol, the limit edged stirs, and contains pure 50-70% to supernatant; Leave standstill 12-24h, filter, deposition discards, and filtrates 60～65 ℃ to be evaporated to dried;
In the prescription ratio, with above-mentioned five kinds of dry powder blend;
The active substance that above technology obtains mixes with the medicine acceptable carrier, processes according to the galenic pharmacy routine techniques.
2. method for preparing according to claim 1 is characterized in that, said compositions is processed into by following bulk drugs process:
Radix et Rhizoma Rhei (stir-fried with wine) 5-7 part prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice 10-20 part Semen Cassiae 20-40 part
Ramulus Uncariae Cum Uncis 20-40 part Fructus Leonuri 20-40 part Spica Prunellae 40-50 part
Pheretima 20-40 part Monas cuspurpureus Went 5-7 part.
3. method for preparing according to claim 2 is characterized in that, said compositions is processed into by following bulk drugs process:
30 parts of 15 parts of Semen Cassiaes of 6 parts of prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice of Radix et Rhizoma Rhei (stir-fried with wine)
45 parts of 30 parts of Spica Prunellaes of 30 parts of Fructus Leonuris of Ramulus Uncariae Cum Uncis
6 parts in 30 parts of Monas cuspurpureus Went of Pheretima.
4. according to said any one method for preparing of claim 1-3, wherein said compositions contains the medicine acceptable carrier.
5. according to said any one method for preparing of claim 4, wherein said compositions is any pharmaceutically useful dosage form.
6. according to said any one method for preparing of claim 5, wherein said compositions is a peroral dosage form.
7. the described method for preparing of claim 1 is characterized in that, may further comprise the steps:
Radix et Rhizoma Rhei (stir-fried with wine) and Semen Cassiae add 8 times 50% ethanol extraction 1h, filter, and medicinal residues add 8 times 50% ethanol extraction 1h, filter; Medicinal residues discard, merge extractive liquid,, 60～65 ℃ of 4 times of volumes that are evaporated to medical material, 15 times of volumes of thin up to medical material; Leave standstill 12h, centrifuging and taking supernatant, D101 purification (medical material amount 1.7 times), last appearance; Washing (5 column volumes), 80% ethanol elution (16 column volumes), eluent is evaporated to dried for 60～65 ℃;
Prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice adds 8 times 70% ethanol extraction 1h, filters, and medicinal residues add 8 times 70% ethanol extraction 1h, filters; Medicinal residues discard, merge extractive liquid,, 60～65 ℃ of 3 times of volumes that are evaporated to medical material; After being cooled to room temperature, adding concentrated hydrochloric acid and regulate pH to 1.5,12h is left standstill in cold preservation; Filter, filtrating discards, and gets the deposition part and is drying to obtain;
Spica Prunellae adds 13 times of water loggings bubble 0.5h, be heated to boiling after, extract 1h, filter; Medicinal residues add 13 times of decoctings and boil 1h, filter, and medicinal residues discard, and extracted twice liquid is merged; After being cooled to room temperature, D101 purification (medical material 1.5 times), last appearance; Washing (5 column volumes), 80% ethanol elution (medical material 15 times), eluent is evaporated to dried for 60～65 ℃;
Ramulus Uncariae Cum Uncis and Fructus Leonuri add 9 times of water loggings bubble 0.5h, be heated to boiling after, extract 1h, filter; Medicinal residues add 9 times of decoctings and boil 1h, filter, and medicinal residues discard, and extracted twice liquid is merged; After being cooled to room temperature, D101 purification (medical material 1.5 times), last appearance; Washing (5 column volumes), 80% ethanol elution (medical material 15 times), eluent is evaporated to dried for 60～65 ℃;
Pheretima and Monas cuspurpureus Went add 8 times of water loggings bubble 0.5h, be heated to boiling after, extract 1h, filter, medicinal residues add 7 times of decoctings and boil 1h; Filter, medicinal residues discard, and extracted twice liquid is merged, and 60～65 ℃ are evaporated to D60=1.05-1.10, get concentrated solution; After being cooled to room temperature, add 95% ethanol precipitate with ethanol, the limit edged stirs, and contains alcohol 70% to supernatant; Leave standstill 12h, filter, deposition discards, and filtrates 60～65 ℃ to be evaporated to dried;
In the prescription ratio, with above-mentioned five kinds of dry powder blend;
The pharmaceutically active substance that more than obtains, this active substance mixes with the medicine acceptable carrier, processes according to the galenic pharmacy routine techniques.
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