CN102357183A - Traditional Chinese medicament for curing cough and preparation method thereof - Google Patents
Traditional Chinese medicament for curing cough and preparation method thereof Download PDFInfo
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- CN102357183A CN102357183A CN2011103279145A CN201110327914A CN102357183A CN 102357183 A CN102357183 A CN 102357183A CN 2011103279145 A CN2011103279145 A CN 2011103279145A CN 201110327914 A CN201110327914 A CN 201110327914A CN 102357183 A CN102357183 A CN 102357183A
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- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 210000000534 thyroid cartilage Anatomy 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
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- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a traditional Chinese medicament for curing cough and a preparation method thereof. 100 parts of ephedra, 10 parts of fritillaria cirrhosa, 50 parts of loguat leaves, 50 parts of radix asteris, 60 parts of pericarpium papaveris, 50 parts of scutellaria baicalensis, 50 parts of liquorice and 0.3 part of menthol crystal are taken as raw materials of the traditional Chinese medicament. The traditional Chinese medicament is prepared by the raw materials after extraction for purification according to a certain process and auxiliary materials accepted by pharmaceutics. The traditional Chinese medicament for curing the cough has the advantages of being simple, practicable, safe and effective in preparation process and remarkable in pharmacodynamic effects.
Description
Technical field
The present invention relates to a kind of Chinese medicine preparation of treating cough and preparation method thereof, belong to the pharmaceutical preparations technology field.
Background technology
Cough is clinical common main suit's disease, and multiple disease such as flu, acute and chronic tracheitis, pneumonia etc. all can occur.Cough has important respiratory tract defense function; Can remove the foreign body and the storage of inhaling human respiratory and stay the secretions in the respiratory tract, but serious and lasting cough makes patient uncomfortable, hinders to sleep and have a rest; The infringement of respiratory tissues and function can be caused, and the whole body multiple complications can be caused.Also patient's psychology and social function caused negative effect simultaneously, reduce life quality.Make it to alleviate so need to use cough medicine, expectorant is arranged and the violent person that coughs, need expectorant and antitussive to use simultaneously, so cough-relieving medicament clinical demand amount is bigger.Motherland's medical science thinks, pathogens such as the human feeling the wind comes from outward, trembles with fear, wets, heat cause gas to be stopped up to have some setbacks then cough, ailment said due to cold or exposure, pathogenic heat heat-transformation, intrinsic heat to hinder water and shut down and then give birth to expectorant.Because all poison invasion and attack of exopathogen flesh table, inhibited pulmonary QI then causes the functional disorder of lung controlling dispersing outward and inwards, regulating fluid apssage; Thereby because of weakness of the spleen and stomach; Essence of water and grain is from positizing, and then then is converted into and violates on the phlegm-damp in lung, stops amassing with the bringing about the spread of body fluid; Scurry heat-transformation on the evil poison and very thirsty, and then the empty symptom such as weak of body occurs.General its etiology and pathogenesis, stopping up lung with wind-heat invading the lung, wind-cold affecting lung, phlegm-damp is main symptom, and the rule of treatment is worked as reducing heat and dispersing lung-QI, and expectorant cough suppressant and anti-asthmatic is a method, so just can reach the purpose of curing the disease of treating both the principal and secondary aspects of a disease.
Between this; We have successively applied for patent of invention and have obtained mandate, are in 02153462.4 patent application document at application number, mainly are to protect from the aspects such as method for preparing of preparation prescription and oral liquid; The present invention carries out a large amount of experimentatioies on this basis; With further replenishment of process method for preparing, improving medicine stability and bioavailability is purpose, and creationary a kind of Chinese medicine preparation of treating cough of succeeding in developing.
Summary of the invention
The object of the invention is to provide a kind of steady quality, and curative effect is reliable, the Chinese medicine preparation of the treatment cough that bioavailability is high.
Another object of the present invention is to provide the method for preparing of the Chinese medicine preparation of this treatment cough; The each component compatibility is reasonable in this method; Process stabilizing, the Chinese medicine preparation that makes are through corresponding pharmacodynamics test research, and the result shows this Chinese medicine preparation stable curative effect, effective, reliable.
The raw material of Chinese medicine preparation of the present invention consists of: 100 parts in Herba Ephedrae, 10 parts of Bulbus Fritillariae Cirrhosaes, 50 parts of Folium Eriobotryaes, 50 parts of Radix Asteriss, 60 parts of Pericarpium Papaveriss, 50 parts of Radix Scutellariaes, 50 parts in Radix Glycyrrhizae, 0.3 part of Mentholum;
Technical scheme of the present invention is realized by following step:
(1) get Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, add sour water and soak back decoction extraction, it is subsequent use that extracting solution is condensed into clear paste;
(2) Radix Scutellariae and Radix Asteris are added certain density soak with ethanol after, reflux, extract,, extracting solution reclaims ethanol and is condensed into clear paste to be continued to employ;
(3) Folium Eriobotryae and Radix Glycyrrhizae decocte with water are together extracted, add ethanol after filtrating suitably concentrates and make and contain alcohol and measure, leave standstill, reclaim ethanol and be condensed into clear paste subsequent use to finite concentration;
(4) process Mentholum solution with 95% dissolve with ethanol Mentholum after, use beta-cyclodextrin inclusion compound, the Mentholum Benexate Hydrochloride subsequent use;
(5) with glycerol, gelatin and water heat according to a certain percentage be swelled into glue after, add opacifier, antiseptic, degasification, it is subsequent use to process rubber;
(6) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder; With the Mentholum Benexate Hydrochloride mix homogeneously described in (4), and add dispersant, suspending agent after stirring capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5); Compacting promptly gets.
Technical scheme of the present invention is specifically realized by following steps:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris; Adding is after 8～12 times of amounts, pH are 3.0～benzothiophene acid water logging bubble, 20～40min with the medical material weight ratio; Heating and refluxing extraction 1～3 time, it is that 1.0～1.2 clear paste is subsequent use that each 0.5h～2h, extracting solution are condensed into relative density;
(2) with Radix Scutellariae and Radix Asteris medical material; Add with the medical material weight ratio be after 6～10 times of amounts, concentration are soak with ethanol 20～40min of 50%～90%; Reflux, extract, 2～3 times, each 1h～2h, it is subsequent use to be condensed into relative density behind the extracting solution decompression recycling ethanol and to be 1.0～1.2 clear paste;
(3) Folium Eriobotryae and Radix Glycyrrhizae add together with the medical material weight ratio be 6～10 times of water gagings; Decoct and extract 2～3 times; Add ethanol after each 1h～2h, extracting solution suitably concentrate and make and contain the alcohol amount, leave standstill 24～48h to 60%～80%; Filter filtrate recycling ethanol and to be condensed into relative density be that 1.0～1.2 clear paste is subsequent use;
(4) process 2%～10% Mentholum solution with 95% dissolve with ethanol Mentholum after, use the beta-cyclodextrin inclusion compound of doubly measuring as 2-6 with the medical material weight ratio, the Mentholum Benexate Hydrochloride is subsequent use;
(5) with glycerol, gelatin and water by weight being 0.2～1.0: after 1.0: 1.0～1.8 heating are swelled into glue; Adding and glycerol, gelatin and water gross weight than be 1%～3% opacifier and with glycerol, gelatin and water gross weight than the antiseptic that is 2%～6%; Degasification, it is subsequent use to process rubber;
(6) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder; With the Mentholum Benexate Hydrochloride mix homogeneously described in (4), and add dispersant, suspending agent after stirring capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5); Compacting promptly gets.
The final optimized technical scheme of preparation of the present invention is following:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, add with the medical material weight ratio be that 10 times of amounts, pH are after 4.0 sour water soaks 30min, heating and refluxing extraction 2 times, 1h at every turn, merging filtrate and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(2) get Radix Scutellariae and Radix Asteris medical material, add with the medical material weight ratio be after 8 times of amounts, concentration are 70% soak with ethanol 30min, reflux, extract, 2 times, each 1h, filtration, merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.1 clear paste is subsequent use,
(3) Folium Eriobotryae and Radix Glycyrrhizae add together with the medical material weight ratio be 8 times of water gagings, decoct to extract each 1h 2 times; Filter, after merging filtrate and suitable the concentrating, adding ethanol makes and contains the alcohol amount to 70%; Leave standstill 24h, filter, filtrate recycling ethanol and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(4) process 5% Mentholum solution with 95% dissolve with ethanol Mentholum after, use with the medical material weight ratio be the beta-cyclodextrin inclusion compound of 3 times of amounts, the Mentholum Benexate Hydrochloride is subsequent use;
(5) with glycerol, gelatin and water by weight being after heating in 0.5: 1.0: 1.2 is swelled into glue, adding and glycerol, gelatin and water gross weight be than being 2% opacifier, 5% antiseptic, degasification, it is subsequent use to process rubber;
(6) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder; With the Mentholum Benexate Hydrochloride mix homogeneously described in (4), and add dispersant, suspending agent after stirring capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5); Compacting promptly gets.
What the opacifier among the preparation technology of above-mentioned Chinese medicine preparation was selected for use is a kind of or mixture in titanium dioxide, the zinc oxide; Antiseptic is selected for use is one or more the mixture in benzoic acid, sodium benzoate, ethyl hydroxybenzoate, sorbic acid, the potassium sorbate; What dispersant was selected for use is polyethylene glycols or vegetable oil; Suspending agent is selected for use is one or more the mixture in Cera Flava, lecithin, aluminum monostearate, the propylene glycol.
Chinese medicine preparation of the present invention has heat clearing away, and lung qi dispersing is relievingd asthma, the effect of preventing phlegm from forming and stopping coughing.Be used for cough with copious phlegm or ungratifying ejection of phlegm due to wind-heat invading the lung, the stagnation of fire in the interior, laryngopharynx swelling and pain, fullness in the chest and shortness of breath, cold cough and acute and chronic bronchitis are seen above-mentioned card marquis person.We than the patent 02153462.4 in first to file, mainly have following creationary useful technique effect in the middle of the research process of reality:
1. the extraction of medical material, purification, molding research:
A. Chinese medicine composition of the present invention is made up of 8 flavor Chinese crude drugs such as Bulbus Fritillariae Cirrhosae, Herba Ephedrae, Radix Asteris and Folium Eriobotryae, and its prescription is quite simplified proper; Its epheday intermedia, Bulbus Fritillariae Cirrhosae and Pericarpium Papaveris contain a large amount of alkaloids effective ingredient, so we adopt the mode of acid extraction to extract; Contain a large amount of pure dissolubility effective ingredient in Radix Scutellariae and the Radix Asteris 2 flavor medical materials, for example therefore baicalin, shionon etc., after we carry out ethanol extraction with it, can reach the purpose of efficient medication like this; Contain triterpenes components in Folium Eriobotryae and the Radix Glycyrrhizae,, select the precipitate with ethanol impurity removal and purification then for use earlier with its effective ingredient of water boiling and extraction.Above extraction and purification process, the physicochemical property of each medical material in the prescription of comprehensively having investigated is reasonably planned as a whole its process route of optimizing the most of design, finally processes science, Chinese medicine preparation efficiently.
B. Mentholum is after fresh stem and the Ye Jing steam distillation of lip type section plant Herba Menthae gets Oleum menthae, from Oleum menthae, extracts and a kind of unsaturated cyclic alcohol of obtaining again, and it is the white crystalline powder of a kind of colourless needle-like or prism-shaped.The Mentholum highly volatile; Fusing point is 42～45 ℃, not only produces strong impulse in process of production, is prone to fusion when preparation temperature is high; And have a strong impact on the stability of product; Therefore, we adopt the beta-cyclodextrin inclusion compound technology to it, with operability and the stability that improves its preparation technology and end product quality.
C. its pharmaceutical dosage form of application number 02153462.4 contrast groups is an oral liquid, belong to a kind of clinical practice dosage form of routine, and technology of the present invention belongs to the Chinese medicinal soft capsule preparation, has good, the advantages such as bioavailability is high, good stability of plasticity.In development process of the present invention, we are through research constantly and accidental exploration, the final creationary moulding process that opens the soft capsule of stable, good moldability, thus huge market potential is provided for the present invention program's realization.
2. pharmacodynamic study
Owing to content of the present invention is to be to improve on 02153462.4 basis at application number, so our high spot reviews and this public technology comparison of project in pharmacodynamics test.Proportion of composing is identical because both write out a prescription, but it is preparation, the different Chinese medicine preparation of moulding process, so we are the diversity that representative is explained both with best preparation technology all.At first; Because the present invention program's core is created point and is the huge advantage in medicinal material extract, the purifying process; Therefore we are in line with contrast experiment's principle parallel, reasonable, that practice thrift; We forgo because the dosage form difference is brought different must the disturbing of curative effect under study for action, promptly respectively with the two middle article of all processing according to extraction process scheme separately, compare through zooperal method.In addition, we process finished product preparation separately to the two according to optimum extraction process scheme separately, compare for oral the taking of patient through the mode of clinical research.In the test of pesticide effectiveness we mainly from antitussive, eliminate the phlegm, relieving asthma, aspect such as antiinflammatory action studies; Clinical trial is from medicine cough-relieving curative effect and rate of adverse reactions, degree and the aspect such as lapse to and investigate; In the hope of reaching science, effectively illustrate the remarkable curative effect of medication of content of the present invention, finally the present invention is described the useful technique effect that is reached.
The preparation of experiment drug group:
The preparation of drug study group A. of the present invention:
(1) with Bulbus Fritillariae Cirrhosae 10g, Herba Ephedrae 100g and Pericarpium Papaveris 60g, add with the medical material weight ratio be that 10 times of amounts, pH are after 4.0 sour water soaks 30min, heating and refluxing extraction 2 times, 1h at every turn, merging filtrate and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(2) get Radix Scutellariae 50g and Radix Asteris 50g medical material, add with the medical material weight ratio be after 8 times of amounts, concentration are 70% soak with ethanol 30min, reflux, extract, 2 times, each 1h, filtration, merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(3) Folium Eriobotryae 50g and Radix Glycyrrhizae 50g add together with the medical material weight ratio be 8 times of water gagings, decoct to extract each 1h 2 times; Filter, after merging filtrate and suitable the concentrating, adding ethanol makes and contains the alcohol amount to 70%; Leave standstill 24h, filter, filtrate recycling ethanol and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(4) process 5% Mentholum solution with 95% dissolve with ethanol Mentholum 0.3g after, use the 0.9g beta-cyclodextrin inclusion compound, the Mentholum Benexate Hydrochloride is subsequent use;
(5) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder,, subsequent use with the Mentholum Benexate Hydrochloride mix homogeneously described in (4); Face with before adding water and be made into certain density medicinal liquid, promptly get article group in the middle of the medicine of the present invention;
(6) with glycerol, gelatin and water by weight be 0.5: 1.0: 1.2 the heating be swelled into glue after; Adding and glycerol, gelatin and water gross weight be than being 2% titanium dioxide, 5% benzoic acid, and degasification is processed behind the rubber and the mixture mix homogeneously described in (5); Add an amount of soybean oil, lecithin stir capsule liquid; The rubber that makes in capsule liquid and above-mentioned (5), compacting promptly gets medicine finished product preparation group of the present invention.
B. the preparation of application number 02153462.4 drug study group:
(1) get Herba Ephedrae 100g, use steam distillation, collect distillate and medicinal liquid, medicinal liquid is subsequent use; Medicinal residues and Bulbus Fritillariae Cirrhosae 10g, Folium Eriobotryae 50g, Radix Asteris 50g, Radix Scutellariae 50g, Pericarpium Papaveris 60g, Radix Glycyrrhizae 50g, decocte with water twice, 2 hours for the first time; 1.5 hours for the second time, merge decoction liquor, filter; Filtrating concentrates with the combining medicine of extracting behind the volatile oil, and the gained clear paste adds ethanol to be made and contain the alcohol amount to 60%, leaves standstill 24 hours; Filter, reclaim ethanol, and continue to be condensed into clear paste;
(2) get Mentholum 0.3g with 3 times of amount beta-cyclodextrin inclusion compounds; The clear paste of gained in above-mentioned (1) is dry and be ground into behind the dried cream powder and Mentholum Benexate Hydrochloride mix homogeneously; Face with before adding water and be made into certain density medicinal liquid, promptly get article group in the middle of application number 02153462.4 medicine;
(3) in (1), in the clear paste of gained, add Mel 50g, sucrose 100g and sodium benzoate 3g, boil, leave standstill, coarse filtration adds distillate and Mentholum, is adjusted to 1000ml with distilled water, promptly gets application number 02153462.4 medicine finished product preparation group.
2.1 laboratory animal: the Cavia porcellus that grows up, the Wistar rat, Kunming kind white mice, the cleaning level is provided by The Fourth Military Medical University's Experimental Animal Center.
2.2 statistical procedures: experimental result is represented with
, adopts the t check to measure the significance of group difference.
2.3 antitussive experimentation:
2.3.1 strong aqua ammonia nebulization:
Get 30 of mices, male and female half and half are divided into 3 groups at random, every group of difference gastric infusion, every day 1 time, 3d continuously.Behind last administration 1h, mice is accepted strong aqua ammonia spraying 10s, after spraying finishes, takes out mice, observes time and number of times that the cough reaction occurs, cough number of times in cough latent period of record mice and the 3min, and the result sees table 1.
Table 1 pair strong aqua ammonia brings out the influence
of mouse cough
Annotate: compare with the normal saline matched group,
*P＜0.05,
*P＜0.01,
* *P＜0.001; Compare with article group in the middle of the application number 02153462.4,
△P＜0.05,
△ △P＜0.01.
Result by table 1 can know: with the normal saline matched group relatively, there is the difference of significance in the evaluation index of the mouse cough that article group and application number 02153462.4 centre article group are all brought out strong aqua ammonia in the middle of the present invention; Compare with article group in the middle of the application number 02153462.4, the article group obviously prolonged in time incubation period of mouse cough in the middle of the present invention, and the cough number of times obviously reduces, and reaches the effect of significant difference.
2.3.2 sulfur dioxide stimulus method:
Get 30 of mices, male and female half and half are divided into 3 groups at random, every group of difference gastric infusion, every day 1 time, 3d continuously.Behind last administration 1h; Get the 25ml glass dish, add 0.5g anhydrous sodium sulfite and 50% sulphuric acid 5ml, fasten glass dish with the 500ml bell jar; Rapidly mice is put into the bell jar that contains sulfur dioxide; Observe time and number of times that the cough reaction occurs, cough number of times in cough latent period of record mice and the 3min, the result sees table 2.
Table 2 pair sulfur dioxide brings out the influence
of mouse cough
Annotate: compare with the normal saline matched group,
*P＜0.01,
* *P＜0.001; Compare with article group in the middle of the application number 02153462.4,
△P＜0.05.
Result by table 2 can know: with the normal saline matched group relatively, there is the difference of significance in parameter index aspects such as the incubation period of the mouse cough that article group and application number 02153462.4 centre article all bring out sulfur dioxide in the middle of the present invention, number of times; Compare with article group in the middle of the application number 02153462.4, the article group obviously prolonged in time incubation period of mouse cough in the middle of the present invention, and the cough number of times obviously reduces, and all has the effect (P＜0.05) of significant difference.
Can know by table 1,2 result: article group comparison in the middle of article group and the application number 02153462.4 in the middle of the present invention; The index parameter of the mouse cough that strong aqua ammonia is brought out all has more excellent curative effect; And reached the significance difference opposite sex on the statistics, can obvious treatment and the pathological symptom that improves the various kinds cough.
2.4 experimentation of eliminating the phlegm (the phenol red method of trachea section):
Get 30 of mices, male and female half and half are divided into 3 groups at random, and every day is gastric infusion respectively, every day 1 time, 3d continuously.Behind the last administration 30min, lumbar injection 5% phenol red 0.1ml/10g puts to death mice behind 30min; Peel off the trachea surrounding tissue, cut one section trachea, put into the 2ml normal saline from thyroid cartilage to trachea crotch; 2 of the sodium hydroxide of adding 1mol/L; The 546nm colorimetric is calculated phenol red content, and the result sees table 3.
The influence
of the table 3 pair phenol red excretion amount of mice trachea section
Annotate: compare with the normal saline matched group,
*P＜0.01,
* *P＜0.001; Compare with article group in the middle of the application number 02153462.4,
△ △P＜0.01.
Experimental result by table 3 can be known: with the normal saline group relatively, article group and application number 02153462.4 centre article group in the middle of the present invention all can make the phenol red excretion amount of mice trachea section showed increased, and have all reached the effect of highly significant difference; Compare with article group in the middle of the application number 02153462.4, the phenol red excretion amount of the mice trachea showed increased of article group in the middle of the present invention, and reach significance difference opposite sex effect (P＜0.01); Above experimental result shows: the article group can significantly increase the phenol red excretion amount of mice trachea than article group in the middle of the application number 02153462.4 in the middle of the present invention, improves the permeability of trachea significantly, fully demonstrates the good phlegm-dispelling functions of the middle article group of the present invention.
2.5 Antiasthmatic Action:
Get 30 of Cavia porcelluss; Male and female half and half; Be divided into 3 groups at random; Brings out Cavia porcellus asthma according to following method before the administration: Cavia porcellus is put into glass bell jar, spray into 2% acecoline and 0.1% histamine phosphate isometric(al) mixed liquor 15s, observe the asthma incubation period (before the administration) of Cavia porcellus with the pressure of 400mmHg.Play every group of gastric infusion respectively next day, every day 1 time, 3d continuously.Behind last administration 1h, bring out asthma once more with above-mentioned same method, the asthma incubation period of Cavia porcellus after the mensuration administration, both make difference and calculate time difference then, and the result sees table 4.
The influence of table 4 pair Cavia porcellus asthma
Annotate: compare with the normal saline matched group,
*P＜0.01,
* *P＜0.001; Compare with article group in the middle of the application number 02153462.4,
△P＜0.05.
Experimental result by table 4 can be known: compare with the normal saline group; Article group and application number 02153462.4 middle article group can make that all Cavia porcellus asthma obviously prolongs incubation period in the middle of the present invention; And all reached the effect of significant differences, shown that the experiment drug group is effective; Compare with article group in the middle of the application number 02153462.4; The middle article group of the present invention has obviously prolonged acetylcholine and histamine is united the Cavia porcellus asthma incubation period of bringing out; And reached the effect of significant difference; Show that the extraction and purification process of preparation of the present invention obviously is superior to the effect of 02153462.4 group of application number, it has the better curative effect of relievining asthma.
2.6 antiinflammatory action research:
2.6.1 the influence of the mice ear that xylol causes:
Get 40 of mices, be divided into 4 groups at random, 10 every group, gastric infusion 1 time every day (the drug group dosage is in the crude drug amount); Continuous 5 days, after the last administration 30 minutes, xylene only dripped in mouse right ear by 20 μ l/ carry on the back; Put to death animal after 15 minutes, with the 5mm card punch along the left and right sides auricle same area punching draw materials, weigh respectively; Represent the swelling degree with the two auricle method of double differences, respectively organize the swelling degree and obtain and press down swollen rate, the result sees table 5.
Press down swollen rate=(auris dextra sheet weight-left auricle weight)/left ear weight * 100%
The influence of the mice ear that table 5 xylol causes
Annotate: compare with the normal saline matched group,
*P＜0.05,
*P＜0.01,
* *P＜0.001; Compare with article group in the middle of the application number 02153462.4,
△P＜0.05.
Experimental result by table 5 shows: compare with the normal saline group, article group and application number 02153462.4 middle article group all have tangible antiphlogistic effects in the middle of aspirin matched group, the present invention; Compare with article group in the middle of the application number 02153462.4, article group xylol causes that mice two auricle weight differences obviously reduce in the middle of the present invention, and has the significant difference of statistical significance; In addition, its antiinflammatory curative effect of medicine of the present invention is lower than the aspirin positive controls slightly, and this also is the antibiotic characteristics that meet Chinese medicine preparation.
2.6.2 the influence of ankle swelling in rat due to the on Carrageenan:
Get 40 of rats, be divided into 4 groups at random, 10 every group; Gastric infusion 1 time every day (the drug group dosage is in the crude drug amount), continuous 5 days, after the last administration after 30 minutes; Cause inflammation in right back ankle subcutaneous injection 1% carrageenin 0.1ml; Adopt slide gauge 0h, 4h, 8h after administration to measure right back sufficient thickness, then with cause that the difference of right back sufficient thickness is its swelling degree before the inflammation, the result sees table 6.
The influence of ankle swelling in rat due to table 6 on Carrageenan
Annotate: compare with the normal saline matched group,
*P＜0.01,
* *P＜0.001; Compare with article group in the middle of the application number 02153462.4,
△P＜0.05,
△ △ △P＜0.001.
Experimental result by table 6 shows: compare with the normal saline group, article group and application number 02153462.4 middle article group all have very significantly antiphlogistic effects in the middle of aspirin matched group, the present invention; With article group in the middle of the application number 02153462.4 relatively, in the middle of the present invention the article group after administration due to 4h, the 8h on Carrageenan ankle swelling in rat degree effect of dwindling is significantly arranged, reached significant difference; Above results suggest: the article group has more excellent antiinflammatory action in the middle of the present invention.
2.6.3 to the granulomatous inhibitory action of rat inflammation:
Get 40 of rats, be divided into 3 groups at random, 10 every group.Anaesthetize with 3% pentobarbital sodium earlier respectively for every group, cut armpit skin in the sterile working down, every Mus buries in the oxter subcutaneous with the little Cotton Gossypii grain of sterilizing (weight is 10g); Gastric infusion 1 time every day (the drug group dosage is in the crude drug amount), successive administration 7d, put to death animal next day after the last administration; Take out granuloma,, place 6h in the exsiccator then at 80 ℃ of dry 1h; Weigh and deduct Cotton Gossypii weight; The granuloma net weight, from the suppression ratio of the net weight of matched group and administration group calculating medicine to inflammatory granuloma, the result sees table 7.
The granulomatous inhibitory action of table 7 pair rat inflammation
Annotate: compare with the normal saline matched group,
*P＜0.01,
* *P＜0.001; Compare with article group in the middle of the application number 02153462.4,
△ △P＜0.01,
△ △ △P＜0.001.
Experimental result by table 7 shows: compare with the normal saline group, each administration group all can significantly reduce the granulomatous weight of rat inflammation, and is wherein obvious with the aspirin matched group, and the article group is taken second place in the middle of the present invention; Compare with article group in the middle of the application number 02153462.4, the article group has obvious suppression effect more to the rat inflammation granuloma in the middle of the present invention, and has the significant difference on the statistical significance.
Show that through above-mentioned antiinflammatory experimental studies results the article group all has good inhibition effect to all kinds of active chronic inflammations in the middle of the present invention, its comprehensive therapeutic effect is superior to application number 02153462.4 contrast groups.
In addition, technology contents of the present invention is on the basis of application number 02153462.4, the Chinese medicine preparation of the treatment cough of succeeding in developing in conjunction with the new technique of modern Chinese medicine development, and in order to verify the final curative effect of this Chinese medicine finished product preparation, we have carried out clinical trial.Select 405 example cough patients that this medicine is carried out clinical observation on the therapeutic effect, the result is reported as follows at present.
1 object and method
1.1 object of study: select to use between year December the whole outpatient services and the inpatient of soft capsule of the present invention and application number 02153462.4 oral liquid (by above-mentioned experiment medication preparation), totally 405 examples from January, 2009 to 2010.
1.2 medical diagnosis on disease standard: the antitussive medicine clinical trial guideline according to the Ministry of Public Health Committee of Experts works out is divided into 3 degree with cough: slight cough (+): be interrupted cough, not influence work life; Moderate cough (++): between slight and severe; The severe cough (+++): frequently cough or apasm of coughing influences the work life.
1.3 curative effect diagnostic criteria: cough control fully after the medication: the cough degree transfers (one) to by (+++); Produce effects: the cough degree transfers (+) to by (+++) or is transferred to (one) by (++); Take a turn for the better: the cough degree transfers (+) to by (++) or is transferred to (one) by (+); Invalid: cough does not have improvement.Total effective rate=(controlling routine number+produce effects example number fully)/total inspection example number * 100%.
1.4 adverse effect evaluation: the evaluation of adverse effect cause effect relation by the standard of Ministry of Public Health ADR monitoring center promulgation be divided into certainly, probably, maybe, possibly have nothing to do, to be evaluated and can't estimate 6 grade standards; The untoward reaction result divides healing, take a turn for the better, have sequela and because of dead 4 of ADR.
1.5 the reasonable in-service evaluation of medicine: the evaluation of drug use reasonability divides rationally, basically rationally with unreasonable 3 types.
2 results
2.1 ordinary circumstance: have 136 examples take soft capsule of the present invention (10g/ time, 3 times/d), wherein male 69 examples, women 67 examples, year mean age (48 ± 10); 132 examples take application number 02153462.4 oral liquid (10mi/ time, 3 times/d), wherein male 65 examples, women 67 examples, in year mean age (46 ± 8), 137 examples are taken placebo, wherein male 67 examples, women 70 examples, mean age (46 ± 10) year.186 examples are acute bronchitis companion cough among all patients, and 110 examples are chronic bronchitis companion cough, and 109 examples are acute upper respiratory tract infection companion cough.
2.2 cough-relieving curative effect: in mostly being before 405 routine patient's medications, severe coughs, wherein moderate person is 270 examples, and severe person is 128 examples.Behind the medication 3d, soft capsule group severe cough person of the present invention reduces 83.22%, application number 02153462.4 oral liquid group severe cough person reduces 62.52%, placebo group severe cough person reduces 0%; Behind the medication 7d, soft capsule group of the present invention does not have that severe cough person, application number 02153462.4 oral liquid group severe cough person reduce 72.14%, placebo group severe cough person reduces 0.8%.It is following to take soft capsule patient therapeutic evaluation result of the present invention: complete control rate 35.55%, obvious effective rate 59.27%, improvement rate 5.18%, total effective rate 100%; It is following to take application number 02153462.4 oral liquid patient therapeutic evaluation result: complete control rate 24.60%; Obvious effective rate 40.78%; Improvement rate 26.94%; Total effective rate 92.32%, both have significant difference aspect complete control rate and the obvious effective rate, and soft capsule of the present invention has better curative effect.
2.3 rate of adverse reactions, degree and lapse to: 4 examples take place in untoward reaction after taking soft capsule of the present invention, and incidence rate is 2.94%, mainly show as slight stomach discomfort 2 examples, xerostomia 2 examples; 6 examples take place in untoward reaction after taking application number 02153462.4 oral liquid, and incidence rate is 4.55%, mainly show as slight stomach discomfort 3 examples, xerostomia 3 examples; 2 examples take place in untoward reaction after taking placebo, and incidence rate is 1.46%, mainly show as slight stomach discomfort 2 examples.The untoward reaction degree is slightly, and lapsing to of untoward reaction is improvement, no sequel and because of the ADR death cases, and each organizes untoward reaction does not have the significance difference opposite sex.
Show according to above research contents; Characteristics such as Chinese medicinal soft capsule agent of the present invention has steady quality, bioavailability is high, and is safe and efficient, its drug action obviously is superior to 02153462.4 group of application number; No matter its beneficial effect is from the extraction and purification process of medicine; Still be the forming technique of soft capsule, all effectively guaranteed the excellent results of this preparation medicine, this will bring great potential and development space for the clinical practice of this Chinese medicine preparation.
The specific embodiment
Below be the specific embodiment of content of the present invention, be used for setting forth the technical scheme that present specification is wanted the technical solution problem, help it will be apparent to those skilled in the art that content of the present invention.But the realization of technical scheme of the present invention is not limited to these embodiment.
Embodiment 1
A. raw material is formed: Herba Ephedrae 100g, Bulbus Fritillariae Cirrhosae 10g, Folium Eriobotryae 50g, Radix Asteris 50g, Pericarpium Papaveris 60g, Radix Scutellariae 50g, Radix Glycyrrhizae 50g, Mentholum 0.3g;
B. preparation technology: with 8 flavor raw material of Chinese medicine among the above-mentioned A, by following procedure:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, add with the medical material weight ratio be that 10 times of amounts, pH are after 4.0 sour water soaks 30min, heating and refluxing extraction 2 times, 1h at every turn, merging filtrate and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(2) get Radix Scutellariae and Radix Asteris medical material, add with the medical material weight ratio be after 8 times of amounts, concentration are 70% soak with ethanol 30min, reflux, extract, 2 times, each 1h, filtration, merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(3) Folium Eriobotryae and Radix Glycyrrhizae add together with the medical material weight ratio be 8 times of water gagings, decoct to extract each 1h 2 times; Filter, after merging filtrate and suitable the concentrating, adding ethanol makes and contains the alcohol amount to 70%; Leave standstill 24h, filter, filtrate recycling ethanol and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(4) process 5% Mentholum solution with 95% dissolve with ethanol Mentholum after, use with the medical material weight ratio be the beta-cyclodextrin inclusion compound of 3 times of amounts, the Mentholum Benexate Hydrochloride is subsequent use;
(5) with glycerol, gelatin and water by weight being after heating in 0.5: 1.0: 1.2 is swelled into glue, adding and glycerol, gelatin and water gross weight be than being 2% titanium dioxide, 5% benzoic acid, degasification, it is subsequent use to process rubber;
(6) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder; With the Mentholum Benexate Hydrochloride mix homogeneously described in (4), add an amount of soybean oil, lecithin stir capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5); Compacting promptly gets.
Embodiment 2
A. raw material is formed: Herba Ephedrae 100g, Bulbus Fritillariae Cirrhosae 10g, Folium Eriobotryae 50g, Radix Asteris 50g, Pericarpium Papaveris 60g, Radix Scutellariae 50g, Radix Glycyrrhizae 50g, Mentholum 0.3g;
B. preparation technology: with 8 flavor raw material of Chinese medicine among the above-mentioned A, by following procedure:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, add with the medical material weight ratio be that 8 times of amounts, pH are after 3.0 sour water soaks 20min, heating and refluxing extraction 3 times, 0.5h at every turn, merging filtrate and to be condensed into relative density be that 1.0 clear paste is subsequent use;
(2) get Radix Scutellariae and Radix Asteris medical material, add with the medical material weight ratio be after 6 times of amounts, concentration are 90% soak with ethanol 40min, reflux, extract, 3 times, each 2h, filtration, merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.0 clear paste is subsequent use;
(3) Folium Eriobotryae and Radix Glycyrrhizae add together with the medical material weight ratio be 10 times of water gagings, decoct to extract each 2h 3 times; Filter, after merging filtrate and suitable the concentrating, adding ethanol makes and contains the alcohol amount to 60%; Leave standstill 48h, filter, filtrate recycling ethanol and to be condensed into relative density be that 1.0 clear paste is subsequent use;
(4) process 2% Mentholum solution with 95% dissolve with ethanol Mentholum after, use with the medical material weight ratio be the beta-cyclodextrin inclusion compound of 2 times of amounts, the Mentholum Benexate Hydrochloride is subsequent use;
(5) with glycerol, gelatin and water by weight being after heating in 1.0: 1.0: 1.8 is swelled into glue, adding and glycerol, gelatin and water gross weight be than being 1% titanium dioxide, 6% benzoic acid, degasification, it is subsequent use to process rubber;
(6) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder; With the Mentholum Benexate Hydrochloride mix homogeneously described in (4), add an amount of Oleum Ricini, Cera Flava stir capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5); Compacting promptly gets.
Embodiment 3
A. raw material is formed: Herba Ephedrae 100g, Bulbus Fritillariae Cirrhosae 10g, Folium Eriobotryae 50g, Radix Asteris 50g, Pericarpium Papaveris 60g, Radix Scutellariae 50g, Radix Glycyrrhizae 50g, Mentholum 0.3g;
B. preparation technology: with 8 flavor raw material of Chinese medicine among the above-mentioned A, by following procedure:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, add with the medical material weight ratio be that 12 times of amounts, pH are after 5.0 sour water soaks 40min, heating and refluxing extraction 1 time, 2h at every turn, merging filtrate and to be condensed into relative density be that 1.2 clear paste is subsequent use;
(2) get Radix Scutellariae and Radix Asteris medical material, add with the medical material weight ratio be after 10 times of amounts, concentration are 50% soak with ethanol 20min, reflux, extract, 2 times, each 1.5h, filtration, merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.2 clear paste is subsequent use;
(3) Folium Eriobotryae and Radix Glycyrrhizae add together with the medical material weight ratio be 6 times of water gagings, decoct to extract each 1.5h 2 times; Filter, after merging filtrate and suitable the concentrating, adding ethanol makes and contains the alcohol amount to 80%; Leave standstill 32h, filter, filtrate recycling ethanol and to be condensed into relative density be that 1.2 clear paste is subsequent use;
(4) process 10% Mentholum solution with 95% dissolve with ethanol Mentholum after, use with the medical material weight ratio be the beta-cyclodextrin inclusion compound of 6 times of amounts, the Mentholum Benexate Hydrochloride is subsequent use;
(5) with glycerol, gelatin and water by weight being after heating in 0.2: 1.0: 1.0 is swelled into glue, adding and glycerol, gelatin and water gross weight be than being 3% titanium dioxide, 2% benzoic acid, degasification, it is subsequent use to process rubber;
(6) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder; With the Mentholum Benexate Hydrochloride mix homogeneously described in (4), add an amount of Macrogol 2000, aluminum monostearate stir capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5); Compacting promptly gets.
Embodiment 4
A. raw material is formed: Herba Ephedrae 100g, Bulbus Fritillariae Cirrhosae 10g, Folium Eriobotryae 50g, Radix Asteris 50g, Pericarpium Papaveris 60g, Radix Scutellariae 50g, Radix Glycyrrhizae 50g, Mentholum 0.3g;
B. preparation technology: with 8 flavor raw material of Chinese medicine among the above-mentioned A, by following procedure:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, add with the medical material weight ratio be that 10 times of amounts, pH are after 5.0 sour water soaks 40min, heating and refluxing extraction 1 time, 2h at every turn, merging filtrate and to be condensed into relative density be that 1.0 clear paste is subsequent use;
(2) get Radix Scutellariae and Radix Asteris medical material, add with the medical material weight ratio be after 10 times of amounts, concentration are 50% soak with ethanol 20min, reflux, extract, 2 times, each 1.5h, filtration, merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.0 clear paste is subsequent use;
(3) Folium Eriobotryae and Radix Glycyrrhizae add together with the medical material weight ratio be 6 times of water gagings, decoct to extract each 1.5h 2 times; Filter, after merging filtrate and suitable the concentrating, adding ethanol makes and contains the alcohol amount to 80%; Leave standstill 32h, filter, filtrate recycling ethanol and to be condensed into relative density be that 1.0 clear paste is subsequent use;
(4) process 10% Mentholum solution with 95% dissolve with ethanol Mentholum after, use with the medical material weight ratio be the beta-cyclodextrin inclusion compound of 6 times of amounts, the Mentholum Benexate Hydrochloride is subsequent use;
(5) with glycerol, gelatin and water by weight being after 0.6: 1.0: 1.2 heating and melting becomes glue, adding and glycerol, gelatin and water gross weight be than being 3% zinc oxide, 2% benzoic acid, degasification, it is subsequent use to process rubber;
(6) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder; With the Mentholum Benexate Hydrochloride mix homogeneously described in (4), add an amount of Macrogol 4000, propylene glycol stir capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5); Compacting promptly gets.
The mixture that zinc oxide in the above-mentioned technology can the different proportionings with zinc oxide of titanium dioxide forms replaces; The mixture that sodium benzoate can form with one or several the different proportionings in benzoic acid, sodium benzoate, ethyl hydroxybenzoate, sorbic acid, the potassium sorbate replaces; Macrogol 4000 can be used acceptable vegetable oil replacement on other polyethylene glycols or the pharmaceutics; Propylene glycol can use two kinds in Cera Flava, lecithin, aluminum monostearate, the propylene glycol perhaps two or more, and the mixture that forms by different proportionings replaces.
Claims (10)
1. Chinese medicine preparation of treating cough is characterized in that it is to be formed by following prepared:
A. raw material is formed: 100 parts in Herba Ephedrae, 10 parts of Bulbus Fritillariae Cirrhosaes, 50 parts of Folium Eriobotryaes, 50 parts of Radix Asteriss, 60 parts of Pericarpium Papaveriss, 50 parts of Radix Scutellariaes, 50 parts in Radix Glycyrrhizae, 0.3 part of Mentholum;
B. preparation technology: with 8 flavor raw material of Chinese medicine among the above-mentioned A, by following procedure:
(1) get Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, add sour water and soak back decoction extraction, it is subsequent use that extracting solution is condensed into clear paste;
(2) Radix Scutellariae and Radix Asteris are added certain density soak with ethanol after, reflux, extract,, extracting solution reclaims ethanol and is condensed into clear paste to be continued to employ;
(3) Folium Eriobotryae and Radix Glycyrrhizae decocte with water are together extracted, add ethanol after filtrating suitably concentrates and make and contain alcohol and measure, leave standstill, reclaim ethanol and be condensed into clear paste subsequent use to finite concentration;
(4) process Mentholum solution with 95% dissolve with ethanol Mentholum after, use beta-cyclodextrin inclusion compound, the Mentholum Benexate Hydrochloride subsequent use;
(5) with glycerol, gelatin and water heat according to a certain percentage be swelled into glue after, add opacifier, antiseptic, degasification, it is subsequent use to process rubber;
(6) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder; With the Mentholum Benexate Hydrochloride mix homogeneously described in (4), and add dispersant, suspending agent after stirring capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5); Compacting promptly gets.
2. a kind of Chinese medicine preparation of treating cough as claimed in claim 1 is characterized in that it is to be formed by following prepared:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris; Adding is after 8～12 times of amounts, pH are 3.0～benzothiophene acid water logging bubble, 20～40min with the medical material weight ratio; Heating and refluxing extraction 1～3 time, it is that 1.0～1.2 clear paste is subsequent use that each 0.5h～2h, extracting solution are condensed into relative density;
(2) with Radix Scutellariae and Radix Asteris medical material; Add with the medical material weight ratio be after 6～10 times of amounts, concentration are soak with ethanol 20～40min of 50%～90%; Reflux, extract, 2～3 times, each 1h～2h, it is subsequent use to be condensed into relative density behind the extracting solution decompression recycling ethanol and to be 1.0～1.2 clear paste;
(3) Folium Eriobotryae and Radix Glycyrrhizae add together with the medical material weight ratio be 6～10 times of water gagings; Decoct and extract 2～3 times; Add ethanol after each 1h～2h, extracting solution suitably concentrate and make and contain the alcohol amount, leave standstill 24～48h to 60%～80%; Filter filtrate recycling ethanol and to be condensed into relative density be that 1.0～1.2 clear paste is subsequent use;
(4) process 2%～10% Mentholum solution with 95% dissolve with ethanol Mentholum after, use the beta-cyclodextrin inclusion compound of doubly measuring as 2-6 with the medical material weight ratio, the Mentholum Benexate Hydrochloride is subsequent use;
(5) with glycerol, gelatin and water by weight being 0.2～1.0: after 1.0: 1.0～1.8 heating are swelled into glue; Adding and glycerol, gelatin and water gross weight than be 1%～3% opacifier and with glycerol, gelatin and water gross weight than the antiseptic that is 2%～6%; Degasification, it is subsequent use to process rubber;
(6) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder; With the Mentholum Benexate Hydrochloride mix homogeneously described in (4), and add dispersant, suspending agent after stirring capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5); Compacting promptly gets.
3. a kind of Chinese medicine preparation of treating cough as claimed in claim 2 is characterized in that it is to be formed by following prepared:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, add with the medical material weight ratio be that 10 times of amounts, pH are after 4.0 sour water soaks 30min, heating and refluxing extraction 2 times, 1h at every turn, merging filtrate and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(2) get Radix Scutellariae and Radix Asteris medical material, add with the medical material weight ratio be after 8 times of amounts, concentration are 70% soak with ethanol 30min, reflux, extract, 2 times, each 1h, filtration, merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(3) Folium Eriobotryae and Radix Glycyrrhizae add together with the medical material weight ratio be 8 times of water gagings, decoct to extract each 1h 2 times; Filter, after merging filtrate and suitable the concentrating, adding ethanol makes and contains the alcohol amount to 70%; Leave standstill 24h, filter, filtrate recycling ethanol and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(4) process 5% Mentholum solution with 95% dissolve with ethanol Mentholum after, use with the medical material weight ratio be the beta-cyclodextrin inclusion compound of 3 times of amounts, the Mentholum Benexate Hydrochloride is subsequent use;
(5) with glycerol, gelatin and water by weight being after heating in 0.5: 1.0: 1.2 is swelled into glue, adding and glycerol, gelatin and water gross weight be than being 2% opacifier, 5% antiseptic, degasification, it is subsequent use to process rubber;
(6) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder; With the Mentholum Benexate Hydrochloride mix homogeneously described in (4), and add dispersant, suspending agent after stirring capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5); Compacting promptly gets.
4. a kind of method for preparing of treating the Chinese medicine preparation of cough as claimed in claim 1 is characterized in that:
A. raw material is formed: 100 parts in Herba Ephedrae, 10 parts of Bulbus Fritillariae Cirrhosaes, 50 parts of Folium Eriobotryaes, 50 parts of Radix Asteriss, 60 parts of Pericarpium Papaveriss, 50 parts of Radix Scutellariaes, 50 parts in Radix Glycyrrhizae, 0.3 part of Mentholum;
B. with 8 flavor raw material of Chinese medicine among the above-mentioned A, press following procedure:
(1) get Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, add sour water and soak back decoction extraction, it is subsequent use that extracting solution is condensed into clear paste;
(2) Radix Scutellariae and Radix Asteris are added certain density soak with ethanol after, reflux, extract,, extracting solution reclaims ethanol and is condensed into clear paste to be continued to employ;
(3) Folium Eriobotryae and Radix Glycyrrhizae decocte with water are together extracted, add ethanol after filtrating suitably concentrates and make and contain alcohol and measure, leave standstill, reclaim ethanol and be condensed into clear paste subsequent use to finite concentration;
(4) process Mentholum solution with 95% dissolve with ethanol Mentholum after, use beta-cyclodextrin inclusion compound, the Mentholum Benexate Hydrochloride subsequent use;
(5) with glycerol, gelatin and water heat according to a certain percentage be swelled into glue after, add opacifier, antiseptic, degasification, it is subsequent use to process rubber;
(6) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder; With the Mentholum Benexate Hydrochloride mix homogeneously described in (4), and add dispersant, suspending agent after stirring capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5); Compacting promptly gets.
5. a kind of method for preparing of treating the Chinese medicine preparation of cough as claimed in claim 4 is characterized in that:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris; Adding is after 8～12 times of amounts, pH are 3.0～benzothiophene acid water logging bubble, 20～40min with the medical material weight ratio; Heating and refluxing extraction 1～3 time, it is that 1.0～1.2 clear paste is subsequent use that each 0.5h～2h, extracting solution are condensed into relative density;
(2) with Radix Scutellariae and Radix Asteris medical material; Add with the medical material weight ratio be after 6～10 times of amounts, concentration are soak with ethanol 20～40min of 50%～90%; Reflux, extract, 2～3 times, each 1h～2h, it is subsequent use to be condensed into relative density behind the extracting solution decompression recycling ethanol and to be 1.0～1.2 clear paste;
(3) Folium Eriobotryae and Radix Glycyrrhizae add together with the medical material weight ratio be 6～10 times of water gagings; Decoct and extract 2～3 times; Add ethanol after each 1h～2h, extracting solution suitably concentrate and make and contain the alcohol amount, leave standstill 24～48h to 60%～80%; Filter filtrate recycling ethanol and to be condensed into relative density be that 1.0～1.2 clear paste is subsequent use;
(4) process 2%～10% Mentholum solution with 95% dissolve with ethanol Mentholum after, use the beta-cyclodextrin inclusion compound of doubly measuring as 2-6 with the medical material weight ratio, the Mentholum Benexate Hydrochloride is subsequent use;
(5) with glycerol, gelatin and water by weight being 0.2～1.0: after 1.0: 1.0～1.8 heating are swelled into glue; Adding and glycerol, gelatin and water gross weight than be 1%～3% opacifier and with glycerol, gelatin and water gross weight than the antiseptic that is 2%～6%; Degasification, it is subsequent use to process rubber;
(6) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder; With the Mentholum Benexate Hydrochloride mix homogeneously described in (4), and add dispersant, suspending agent after stirring capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5); Compacting promptly gets.
6. the method for preparing of the Chinese medicine preparation of the treatment described in claim 4 or 5 cough is characterized in that opacifier selects one or both the mixture in titanium dioxide, the zinc oxide for use.
7. the method for preparing of the Chinese medicine preparation of the treatment described in claim 4 or 5 cough is characterized in that antiseptic selects one or more the mixture in benzoic acid, sodium benzoate, ethyl hydroxybenzoate, sorbic acid, the potassium sorbate for use.
8. the method for preparing of the Chinese medicine preparation of the treatment described in claim 4 or 5 cough is characterized in that dispersant selects polyethylene glycols or vegetable oil for use.
9. the method for preparing of the Chinese medicine preparation of the treatment described in claim 4 or 5 cough is characterized in that suspending agent selects one or more the mixture in Cera Flava, lecithin, aluminum monostearate, the propylene glycol for use.
10. a kind of method for preparing of treating the Chinese medicine preparation of cough as claimed in claim 5 is characterized in that:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, add with the medical material weight ratio be that 10 times of amounts, pH are after 4.0 sour water soaks 30min, heating and refluxing extraction 2 times, 1h at every turn, merging filtrate and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(2) get Radix Scutellariae and Radix Asteris medical material, add with the medical material weight ratio be after 8 times of amounts, concentration are 70% soak with ethanol 30min, reflux, extract, 2 times, each 1h, filtration, merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(3) Folium Eriobotryae and Radix Glycyrrhizae add together with the medical material weight ratio be 8 times of water gagings, decoct to extract each 1h 2 times; Filter, after merging filtrate and suitable the concentrating, adding ethanol makes and contains the alcohol amount to 70%; Leave standstill 24h, filter, filtrate recycling ethanol and to be condensed into relative density be that 1.1 clear paste is subsequent use;
(4) process 5% Mentholum solution with 95% dissolve with ethanol Mentholum after, use with the medical material weight ratio be the beta-cyclodextrin inclusion compound of 3 times of amounts, the Mentholum Benexate Hydrochloride is subsequent use;
(5) with glycerol, gelatin and water by weight being after heating in 0.5: 1.0: 1.2 is swelled into glue, adding and glycerol, gelatin and water gross weight be than being 2% titanium dioxide, 5% benzoic acid, degasification, it is subsequent use to process rubber;
(6) with after the mixing of the clear paste described in (1), (2) and (3) and being dried to dried cream powder; With the Mentholum Benexate Hydrochloride mix homogeneously described in (4), add an amount of soybean oil, lecithin stir capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5); Compacting promptly gets.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1418687A (en) * | 2002-11-29 | 2003-05-21 | 张慧芳 | Medicine composite for treating cough |
| CN1562180A (en) * | 2004-03-17 | 2005-01-12 | 北京奇源益德药物研究所 | Preparation of Chinese traditional medicine for curing cough and preparation method |
| CN1686439A (en) * | 2005-05-08 | 2005-10-26 | 北京正大绿洲医药科技有限公司 | Kelu drip pill used for phlegm transforming cough suppressing and its preparation method |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1418687A (en) * | 2002-11-29 | 2003-05-21 | 张慧芳 | Medicine composite for treating cough |
| CN1562180A (en) * | 2004-03-17 | 2005-01-12 | 北京奇源益德药物研究所 | Preparation of Chinese traditional medicine for curing cough and preparation method |
| CN1686439A (en) * | 2005-05-08 | 2005-10-26 | 北京正大绿洲医药科技有限公司 | Kelu drip pill used for phlegm transforming cough suppressing and its preparation method |
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