CN102357183B - 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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- CN102357183B CN102357183B CN 201110327914 CN201110327914A CN102357183B CN 102357183 B CN102357183 B CN 102357183B CN 201110327914 CN201110327914 CN 201110327914 CN 201110327914 A CN201110327914 A CN 201110327914A CN 102357183 B CN102357183 B CN 102357183B
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- 238000012109 statistical procedure Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 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
- 230000001629 suppression Effects 0.000 description 1
- 210000000534 thyroid cartilage Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- RNWHGQJWIACOKP-UHFFFAOYSA-N zinc;oxygen(2-) Chemical group [O-2].[Zn+2] RNWHGQJWIACOKP-UHFFFAOYSA-N 0.000 description 1
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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 for the treatment of cough and preparation method thereof, belong to the pharmaceutical preparations technology field.
Background technology
Cough is clinical common main suit's disease, and various diseases such as flu, acute and chronic tracheitis, pneumonia etc. all can occur.Cough has important respiratory tract defense function, can remove the foreign body of inhaling human respiratory and store up the secretions of staying in respiratory tract, but serious and lasting cough makes patient uncomfortable, hinder sleep and 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 society function is caused negative effect simultaneously, reduce life quality.Make it to alleviate therefore need to use cough medicine, expectorant is arranged and the more violent person that coughs, need expectorant and antitussive to use simultaneously, therefore cough-relieving medicament clinical demand amount is larger.The pathogens such as motherland's medical science thinks, the human feeling the wind comes from outward, trembles with fear, wets, hot cause gas to be stopped up to have some setbacks cough, ailment said due to cold or exposure, pathogenic heat heat-transformation, intrinsic heat to hinder water and shut down and give birth to expectorant.Due to all poison invasion and attack of exopathogen flesh table; inhibited pulmonary QI; cause 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 is converted into and violates on phlegm-damp in lung, stops amassing with the bringing about the spread of body fluid; alter heat-transformation on evil poison and very thirsty, and then the empty symptom such as weak of body occurs.General its etiology and pathogenesis is stopped up lung as main symptom take wind-heat invading the lung, wind-cold affecting lung, phlegm-damp, and the rule for the treatment of is worked as reducing heat and dispersing lung-QI, and expectorant cough suppressant and anti-asthmatic is method, so just can reach the purpose of curing the disease for the treatment of both the principal and secondary aspects of a disease.
Between this; we have successively applied for patent of invention and have obtained mandate; be in 02153462.4 patent application document at application number; mainly to protect from the aspects such as preparation method of preparation prescription and oral liquid; the present invention carries out a large amount of experimentatioies on this basis; with further replenishment of process preparation method, improving medicine stability and bioavailability is purpose, and creationary a kind of Chinese medicine preparation for the treatment of 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 preparation method of the Chinese medicine preparation of this treatment cough, in the method, the each component compatibility is reasonable, process stabilizing, the Chinese medicine preparation that makes are through corresponding pharmacodynamics test research, and 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, 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, Radix Glycyrrhizae, 0.3 part of Mentholum;
Technical solution of the present invention is realized by following step:
(1) get Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, decoct after the acid adding water soaking and extract, it is standby 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 are decocted with water extraction together, add ethanol after filtrate is suitably concentrated and make and contain alcohol and measure to finite concentration, standing, reclaim ethanol and be condensed into clear paste standby;
(4) make Mentholum solution with 95% dissolve with ethanol Mentholum after, use beta-cyclodextrin inclusion compound, get the Mentholum Benexate Hydrochloride standby;
(5) glycerol, gelatin and water are heated according to a certain percentage be swelled into glue after, add opacifier, antiseptic, degasification is made rubber standby;
(6) clear paste described in (1), (2) and (3) mixed and be dried to dried cream powder after, with the Mentholum Benexate Hydrochloride mix homogeneously described in (4), and after adding dispersant, suspending agent to stir evenly capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5), compacting, and get final product.
Technical solution of the present invention is specifically realized by following steps:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, adding with the medical material weight ratio is after 8～12 times of amounts, pH are 3.0～benzothiophene acid water soaking, 20～40min, heating and refluxing extraction 1～3 time, it is that 1.0～1.2 clear paste is standby that each 0.5h～2h, extracting solution are condensed into relative density;
(2) with Radix Scutellariae and Radix Asteris medical material, adding with the medical material weight ratio is after 6～10 times of amounts, concentration are soak with ethanol 20～40min of 50%～90%, reflux, extract, 2～3 times, each 1h～2h is condensed into relative density and is 1.0～1.2 clear paste standby after the extracting solution decompression recycling ethanol;
(3) Folium Eriobotryae and Radix Glycyrrhizae to add together with the medical material weight ratio be 6～10 times of water gagings, decoct and extract 2～3 times, each 1h～2h, adding ethanol after extracting solution is suitably concentrated makes and contains the alcohol amount to 60%～80%, standing 24～48h, filter filtrate recycling ethanol and to be condensed into relative density be that 1.0～1.2 clear paste is standby;
(4) make 2%～10% Mentholum solution with 95% dissolve with ethanol Mentholum after, using with the medical material weight ratio is the beta-cyclodextrin inclusion compound that 2-6 doubly measures, and gets the Mentholum Benexate Hydrochloride standby;
(5) be after 0.2～1.0: 1.0: 1.0～1.8 heating are swelled into glue by weight with glycerol, gelatin and water, add with glycerol, gelatin and water gross weight and reach with glycerol, gelatin and water gross weight than the antiseptic that is 2%～6% than the opacifier that is 1%～3%, degasification is made rubber standby;
(6) clear paste described in (1), (2) and (3) mixed and be dried to dried cream powder after, with the Mentholum Benexate Hydrochloride mix homogeneously described in (4), and after adding dispersant, suspending agent to stir evenly capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5), compacting, and get final product.
The final preferred technical scheme of preparation of the present invention is as follows:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, adding with the medical material weight ratio is that 10 times of amounts, pH are after 4.0 sour water soaks 30min, heating and refluxing extraction 2 times, each 1h, merging filtrate and to be condensed into relative density be that 1.1 clear paste is standby;
(2) get Radix Scutellariae and Radix Asteris medical material, adding with the medical material weight ratio is after 8 times of amounts, concentration are 70% soak with ethanol 30min, reflux, extract, 2 times, and each 1h filters, the merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.1 clear paste is standby,
(3) Folium Eriobotryae and Radix Glycyrrhizae to add together with the medical material weight ratio be 8 times of water gagings, decoct to extract 2 times each 1h, filter, after merging filtrate and suitable concentrating, add ethanol to make and contain the alcohol amount to 70%, standing 24h filters, filtrate recycling ethanol and to be condensed into relative density be that 1.1 clear paste is standby;
(4) make 5% Mentholum solution with 95% dissolve with ethanol Mentholum after, using with the medical material weight ratio is the beta-cyclodextrin inclusion compound of 3 times of amounts, gets the Mentholum Benexate Hydrochloride standby;
(5) be after heating in 0.5: 1.0: 1.2 is swelled into glue, to add with glycerol, gelatin and water gross weight than being 2% opacifier, 5% antiseptic by weight with glycerol, gelatin and water, degasification is made rubber standby;
(6) clear paste described in (1), (2) and (3) mixed and be dried to dried cream powder after, with the Mentholum Benexate Hydrochloride mix homogeneously described in (4), and after adding dispersant, suspending agent to stir evenly capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5), compacting, and get final product.
Opacifier in the preparation technology of above-mentioned Chinese medicine preparation is selected is a kind of or mixture in titanium dioxide, zinc oxide; Antiseptic is selected is one or more mixture in benzoic acid, sodium benzoate, ethyl hydroxybenzoate, sorbic acid, potassium sorbate; What dispersant was selected is polyethylene glycols or vegetable oil; Suspending agent is selected is one or more mixture in Cera Flava, lecithin, aluminum monostearate, 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, 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 comprised of the 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 Radix Asteris 2 flavor medical materials, therefore such as 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 Radix Glycyrrhizae, first use its effective ingredient of water boiling and extraction, then select the precipitate with ethanol impurity removal and purification.Above extraction and purification process, the physicochemical property of each medical material in the prescription of comprehensively having investigated, reasonably its process route of optimizing the most of overall planning, finally make science, efficient Chinese medicine preparation.
B. Mentholum is after the fresh stem of lip type section plant Herba Menthae and Ye Jing steam distillation get Oleum menthae, then extracts from Oleum menthae and a kind of unsaturated cyclic alcohol of obtaining, 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 produce in process of production strong impulse, easy melting 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 oral liquid, belong to a kind of clinical practice dosage form of routine, and the technology of the present invention belongs to the Chinese medicinal soft capsule preparation, has that plasticity is good, the advantages such as bioavailability is high, good stability.In development process of the present invention, we are through constantly research and accidental exploration, the final creationary moulding process that opens the soft capsule of stable, good moldability, thus provide huge market potential for the present invention program's realization.
2. pharmacodynamic study
To be to improve on 02153462.4 basis at application number due to content of the present invention, so the contrast of we high spot reviews and the disclosure technical scheme in pharmacodynamics test.Because both proportion of composing of writing out a prescription are identical, but it is preparation, the different Chinese medicine preparation of moulding process, so we all illustrate both diversityes take best preparation technology as representative.At first, because the huge advantage that is in medicinal material extract, purifying process is put in the present invention program's core creation, therefore we are in line with contrast experiment's principle parallel, reasonable, that save, we forgo under study for action because the dosage form difference is brought different must the disturbing of curative effect, the middle product that namely will both all make according to extraction process scheme separately respectively compare by zooperal method.In addition, we are to both making separately finished product preparation according to optimum extraction process scheme separately, and the mode by clinical research compares to oral the taking of patient.In the test of pesticide effectiveness we mainly from antitussive, eliminate the phlegm, relieving asthma, the 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, to the remarkable curative effect of medication that reaches science, effectively illustrates content of the present invention, the useful technique effect that the present invention reaches is described finally.
The preparation of Experimental agents group:
A. the preparation of drug study group of the present invention:
(1) with Bulbus Fritillariae Cirrhosae 10g, Herba Ephedrae 100g and Pericarpium Papaveris 60g, adding with the medical material weight ratio is that 10 times of amounts, pH are after 4.0 sour water soaks 30min, heating and refluxing extraction 2 times, each 1h, merging filtrate and to be condensed into relative density be that 1.1 clear paste is standby;
(2) get Radix Scutellariae 50g and Radix Asteris 50g medical material, adding with the medical material weight ratio is after 8 times of amounts, concentration are 70% soak with ethanol 30min, reflux, extract, 2 times, each 1h, filter, the merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.1 clear paste is standby;
(3) to add together with the medical material weight ratio be 8 times of water gagings for Folium Eriobotryae 50g and Radix Glycyrrhizae 50g, decoct and extract 2 times, each 1h, filter, after merging filtrate and suitable concentrating, add ethanol to make and contain the alcohol amount to 70%, standing 24h, filter filtrate recycling ethanol and to be condensed into relative density be that 1.1 clear paste is standby;
(4) make 5% Mentholum solution with 95% dissolve with ethanol Mentholum 0.3g after, use the 0.9g beta-cyclodextrin inclusion compound, get the Mentholum Benexate Hydrochloride standby;
(5) clear paste described in (1), (2) and (3) mixed and be dried to dried cream powder after, with the Mentholum Benexate Hydrochloride mix homogeneously described in (4), standby; Add before use water and be made into certain density medicinal liquid, namely get the middle product group of medicine of the present invention;
(6) be after heating in 0.5: 1.0: 1.2 is swelled into glue by weight with glycerol, gelatin and water, add with glycerol, gelatin and water gross weight than being 2% titanium dioxide, 5% benzoic acid, degasification, make after rubber and the mixture mix homogeneously described in (5), add appropriate soybean oil, lecithin to stir evenly to get capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5), compacting namely 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 standby; Medicinal residues and Bulbus Fritillariae Cirrhosae 10g, Folium Eriobotryae 50g, Radix Asteris 50g, Radix Scutellariae 50g, Pericarpium Papaveris 60g, Radix Glycyrrhizae 50g, decoct with water twice, 2 hours for the first time, 1.5 hours for the second time, merge decoction liquor, filter, filtrate with extract medicinal liquid after volatile oil and merge concentratedly, the gained clear paste adds ethanol to be made and contains the alcohol amount to 60%, standing 24 hours, filter, reclaim ethanol, and continue to be condensed into clear paste;
(2) get Mentholum 0.3g and measure beta-cyclodextrin inclusion compounds with 3 times, the clear paste of gained in above-mentioned (1) is dry and be ground into after dried cream powder and Mentholum Benexate Hydrochloride mix homogeneously, add before use water and be made into certain density medicinal liquid, namely get the middle product group of application number 02153462.4 medicine;
(3) in the clear paste of gained, add Mel 50g, sucrose 100g and sodium benzoate 3g in (1), boil, standing, coarse filtration adds distillate and Mentholum, is adjusted to 1000ml with distilled water, namely gets application number 02153462.4 medicine finished product preparation group.
2.1 laboratory animal: adult guinea pig, 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 with
Expression 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.After last administration 1h, mice is accepted strong aqua ammonia spraying 10s, and after spraying finished, the taking-up mice was observed time and number of times that the cough reaction occurs, records cough latent period and the interior cough of the 3min number of times of mice, the results are shown in Table 1.
Table 1 brings out the impact of mouse cough on strong aqua ammonia
Annotate: compare with the normal saline matched group,
*P＜0.05,
*P＜0.01,
* *P＜0.001; Compare with product group in the middle of application number 02153462.4,
△P＜0.05,
△ △P＜0.01.
As shown in Table 1: with the normal saline matched group relatively, there is the difference of significance in the evaluation index of the mouse cough that in the middle of the present invention, in the middle of product group and application number 02153462.4, the product group is all brought out strong aqua ammonia; Compare with product group in the middle of application number 02153462.4, in the middle of the present invention, the product group obviously extended in time incubation period of mouse cough, 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.After 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, record cough latent period and the interior cough of the 3min number of times of mice, the results are shown in Table 2.
Table 2 brings out the impact of mouse cough on sulfur dioxide
Annotate: compare with the normal saline matched group,
*P＜0.01,
* *P＜0.001; Compare with product group in the middle of application number 02153462.4,
△P＜0.05.
As shown in Table 2: with the normal saline matched group relatively, there is the difference of significance in the parameter index such as the incubation period of the mouse cough that in the middle of the present invention, in the middle of product group and application number 02153462.4, product all bring out sulfur dioxide, number of times aspect; Compare with product group in the middle of application number 02153462.4, in the middle of the present invention, the product group obviously extended in time incubation period of mouse cough, and the cough number of times obviously reduces, and all has the effect (P＜0.05) of significant difference.
By table 1,2 result as can be known: product group comparison in the middle of product group and 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 statistically, can significantly treat and improve the pathological symptom of 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.After last administration 30min, the phenol red 0.1ml/10g of lumbar injection 5%, put to death mice after 30min, peel off the trachea surrounding tissue, cut one section trachea to the trachea crotch from thyroid cartilage, put into the 2ml normal saline, 2 of sodium hydroxide that add 1mol/L, the 546nm colorimetric is calculated phenol red content, the results are shown in Table 3.
The impact of table 3 on the phenol red excretion amount of mice trachea section
Annotate: compare with the normal saline matched group,
*P＜0.01,
* *P＜0.001; Compare with product group in the middle of application number 02153462.4,
△ △P＜0.01.
By the experimental result of table 3 as can be known: with the normal saline group relatively, in the middle of the present invention, product group in the middle of product group and application number 02153462.4, all can make the phenol red excretion amount of mice trachea section showed increased, and all reach the effect of highly significant difference; Compare with product group in the middle of application number 02153462.4, the phenol red excretion amount of the mice trachea showed increased of product group in the middle of the present invention, and reach significance difference opposite sex effect (P＜0.01); Above experimental result shows: in the middle of the present invention, the product group than product group in the middle of application number 02153462.4, can significantly increase the phenol red excretion amount of mice trachea, improves significantly the permeability of trachea, fully demonstrates the good phlegm-dispelling functions of the middle product group of the present invention.
2.5 the research of antiasthmatic effect:
Get 30 of Cavia porcelluss, male and female half and half, be divided at random 3 groups, bring out by the following method Experimental Asthma In Guinea-pigs before administration: Cavia porcellus is put into glass bell jar, pressure with 400mmHg sprays into 2% acecoline and 0.1% histamine phosphate isometric(al) mixed liquor 15s, observes the asthma incubation period (before administration) of Cavia porcellus.Play every group of gastric infusion respectively next day, every day 1 time, 3d continuously.After last administration 1h, again bring out asthma with above-mentioned same method, the asthma incubation period of Cavia porcellus after the mensuration administration, then both make difference and calculate time difference, the results are shown in Table 4.
The impact of table 4 on Experimental Asthma In Guinea-pigs
Annotate: compare with the normal saline matched group,
*P＜0.01,
* *P＜0.001; Compare with product group in the middle of application number 02153462.4,
△P＜0.05.
By the experimental result of table 4 as can be known: with the normal saline group relatively, in the middle of the present invention, product group and the middle product group of application number 02153462.4 all can make Experimental Asthma In Guinea-pigs obviously extend incubation period, and all reached the effect of significant differences, shown that the Experimental agents group is effective; Compare with product group in the middle of application number 02153462.4, the middle product group of the present invention has obviously extended acetylcholine and histamine is united the Experimental Asthma In Guinea-pigs 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 better than 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 impact of the mice ear that xylol causes:
Get 40 of mices, be divided at random 4 groups, 10 every group, gastric infusion 1 time every day (medicine group dosage is in the crude drug amount), continuous 5 days, after the last administration 30 minutes, dimethylbenzene is only dripped in mouse right ear by 20 μ l/ carry on the back, put to death animal after 15 minutes, draw materials along the punching of left and right auricle same area with the 5mm card punch, 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 results are shown in Table 5.
Press down swollen rate=(auris dextra sheet weight-left auricle weight)/left ear weight * 100%
The impact 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 product group in the middle of application number 02153462.4,
△P＜0.05.
Experimental result by table 5 shows: compare with the normal saline group, in the middle of aspirin matched group, the present invention, product group and the middle product group of application number 02153462.4 all have obvious antiphlogistic effects; Compare with product group in the middle of application number 02153462.4, in the middle of the present invention, product group xylol causes that mice two auricle weight differences obviously reduce, and has the significant difference of statistical significance; In addition, its antiinflammatory curative effect of medicine of the present invention is slightly lower than the aspirin positive controls, and this is also the antibiotic characteristics that meet Chinese medicine preparation.
2.6.2 the impact of ankle swelling in rat due on Carrageenan:
Get 40 of rats, be divided at random 4 groups, every group 10, gastric infusion 1 time every day (medicine 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, adopting slide gauge 0h, 4h, 8h after administration to measure right back sufficient thickness, is then its swelling with the difference that causes scorching front right metapedes thickness, the results are shown in Table 6.
The impact 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 product group in the middle of application number 02153462.4,
△P＜0.05,
△ △ △P＜0.001.
Experimental result by table 6 shows: compare with the normal saline group, in the middle of aspirin matched group, the present invention, product group and the middle product group of application number 02153462.4 all have very significantly antiphlogistic effects; With product group in the middle of application number 02153462.4 relatively, in the middle of the present invention the product group after administration due to 4h, 8h on Carrageenan the ankle swelling in rat degree effect of dwindling is significantly arranged, reached significant difference; Above results suggest: in the middle of the present invention, the product group has more excellent antiinflammatory action.
2.6.3 to the granulomatous inhibitory action of rat inflammation:
Get 40 of rats, be divided at random 3 groups, 10 every group.Every group respectively first with 3% pentobarbital sodium anesthesia, cut armpit skin under the sterile working, every Mus buries in the oxter subcutaneous take the little Cotton Gossypii grain (weight is as 10g) of sterilizing, gastric infusion 1 time every day (medicine group dosage is in the crude drug amount), successive administration 7d, put to death animal next day after the last administration, take out granuloma, at 80 ℃ of dry 1h, then place 6h in exsiccator, the deduction Cotton Gossypii weight of weighing gets the granuloma net weight, calculate medicine to the suppression ratio of inflammatory granuloma from the net weight of matched group and administration group, the results are shown in 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 product group in the middle of 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 in the middle of the present invention, the product group is taken second place; Compare with product group in the middle of application number 02153462.4, in the middle of the present invention, the product group has more significantly inhibitory action to the rat inflammation granuloma, and has the significant difference on statistical significance.
Show by above-mentioned antiinflammatory experimental studies results, in the middle of the present invention, the product group all has good inhibition to all kinds of active chronic inflammations, and its comprehensive therapeutic effect is better than application number 02153462.4 contrast groups.
In addition, the technology of the present invention content 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 to carry out clinical observation on the therapeutic effect to this medicine, existing that report the test is as follows.
1 object and method
1.1 object of study: select to use between year December from January, 2009 to 2010 whole outpatient services and the inpatient of soft capsule of the present invention and application number 02153462.4 oral liquid (by above-mentioned Experimental agents preparation), totally 405 examples.
1.2 Disease Diagnosis 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, do not affect Working Life; Moderate cough (++): between slight and severe; The severe cough (+++): frequently cough or apasm of coughing affects Working Life.
1.3 curative effect diagnostic criteria: after medication, cough is controlled fully: the cough degree transfers (one) to by (+++); Produce effects: the cough degree is transferred to (+) or is transferred to (one) by (++) by (+++); Take a turn for the better: the cough degree is transferred to (+) or is transferred to (one) by (+) by (++); Invalid: cough is without taking a turn for the better.Total effective rate=(controlling number of cases+produce effects number of cases fully)/total inspection number of cases * 100%.
1.4 adverse effect evaluation: the standard that the adverse effect Causality assessment is promulgated by Ministry of Public Health ADR monitoring center is divided into certainly, probably, may, may 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 rational application of medicine evaluation: the drug use Rationality Assessment divides rationally, reasonable and unreasonable 3 classes.
2 results
2.1 ordinary circumstance: have 136 examples take soft capsule of the present invention (10g/ time, 3 times/d), male 69 examples wherein, female's 67 examples, year mean age (48 ± 10); 132 examples take application number 02153462.4 oral liquid (10mi/ time, 3 times/d), male 65 examples wherein, female's 67 examples, in year mean age (46 ± 8), 137 examples are taken placebo, male 67 examples wherein, female's 70 examples, mean age (46 ± 10) year.In all patients, 186 examples are acute bronchitis companion cough, 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 cough, wherein moderate person is 270 examples, and severe person is 128 examples.After 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%; After medication 7d, soft capsule group of the present invention without severe cough person, application number 02153462.4 oral liquid group severe cough person reduce 72.14%, placebo group severe cough person reduces 0.8%.Take soft capsule patient therapeutic evaluation result of the present invention as follows: complete control rate 35.55%, obvious effective rate 59.27%, improvement rate 5.18%, total effective rate 100%; Take application number 02153462.4 oral liquid patient therapeutic evaluation result as follows: 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 obvious effective rate, and soft capsule of the present invention has better curative effect.
2.3 rate of adverse reactions, degree and lapse to: after taking soft capsule of the present invention, 4 examples occur in untoward reaction, and incidence rate is 2.94%, and main manifestations is slight stomach discomfort 2 examples, xerostomia 2 examples; After taking application number 02153462.4 oral liquid, 6 examples occur in untoward reaction, and incidence rate is 4.55%, and main manifestations is slight stomach discomfort 3 examples, xerostomia 3 examples; After taking placebo, 2 examples occur in untoward reaction, and incidence rate is 1.46%, and main manifestations is 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 case of ADR death, and each organizes untoward reaction without the significance difference opposite sex.
Show according to above research contents, Chinese medicinal soft capsule agent of the present invention has steady quality, bioavailability is high, the characteristics such as safe and efficient, its drug action obviously is better than 02153462.4 group of application number, no matter its beneficial effect is from the extraction and purification process of medicine, or the forming technique of soft capsule has all effectively guaranteed the excellent results of this preparation medicine, and this will bring for the clinical practice of this Chinese medicine preparation huge potentiality and development space.
The specific embodiment
Be below 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 those skilled in the art to understand content of the present invention.But the realization of technical solution of the present invention is not limited to these embodiment.
Embodiment 1
A. raw material forms: 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, operations in the steps below in above-mentioned A:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, adding with the medical material weight ratio is that 10 times of amounts, pH are after 4.0 sour water soaks 30min, heating and refluxing extraction 2 times, each 1h, merging filtrate and to be condensed into relative density be that 1.1 clear paste is standby;
(2) get Radix Scutellariae and Radix Asteris medical material, adding with the medical material weight ratio is after 8 times of amounts, concentration are 70% soak with ethanol 30min, reflux, extract, 2 times, and each 1h filters, the merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.1 clear paste is standby;
(3) Folium Eriobotryae and Radix Glycyrrhizae to add together with the medical material weight ratio be 8 times of water gagings, decoct to extract 2 times each 1h, filter, after merging filtrate and suitable concentrating, add ethanol to make and contain the alcohol amount to 70%, standing 24h filters, filtrate recycling ethanol and to be condensed into relative density be that 1.1 clear paste is standby;
(4) make 5% Mentholum solution with 95% dissolve with ethanol Mentholum after, using with the medical material weight ratio is the beta-cyclodextrin inclusion compound of 3 times of amounts, gets the Mentholum Benexate Hydrochloride standby;
(5) be after heating in 0.5: 1.0: 1.2 is swelled into glue, to add with glycerol, gelatin and water gross weight than being 2% titanium dioxide, 5% benzoic acid by weight with glycerol, gelatin and water, degasification is made rubber standby;
(6) clear paste described in (1), (2) and (3) mixed and be dried to dried cream powder after, with the Mentholum Benexate Hydrochloride mix homogeneously described in (4), add appropriate soybean oil, lecithin to stir evenly to get capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5), compacting, and get final product.
Embodiment 2
A. raw material forms: 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, operations in the steps below in above-mentioned A:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, adding with the medical material weight ratio is that 8 times of amounts, pH are after 3.0 sour water soaks 20min, heating and refluxing extraction 3 times, each 0.5h, merging filtrate and to be condensed into relative density be that 1.0 clear paste is standby;
(2) get Radix Scutellariae and Radix Asteris medical material, adding with the medical material weight ratio is after 6 times of amounts, concentration are 90% soak with ethanol 40min, reflux, extract, 3 times, and each 2h filters, the merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.0 clear paste is standby;
(3) Folium Eriobotryae and Radix Glycyrrhizae to add together with the medical material weight ratio be 10 times of water gagings, decoct to extract 3 times each 2h, filter, after merging filtrate and suitable concentrating, add ethanol to make and contain the alcohol amount to 60%, standing 48h filters, filtrate recycling ethanol and to be condensed into relative density be that 1.0 clear paste is standby;
(4) make 2% Mentholum solution with 95% dissolve with ethanol Mentholum after, using with the medical material weight ratio is the beta-cyclodextrin inclusion compound of 2 times of amounts, gets the Mentholum Benexate Hydrochloride standby;
(5) be after heating in 1.0: 1.0: 1.8 is swelled into glue, to add with glycerol, gelatin and water gross weight than being 1% titanium dioxide, 6% benzoic acid by weight with glycerol, gelatin and water, degasification is made rubber standby;
(6) clear paste described in (1), (2) and (3) mixed and be dried to dried cream powder after, with the Mentholum Benexate Hydrochloride mix homogeneously described in (4), add appropriate Oleum Ricini, Cera Flava to stir evenly to get capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5), compacting, and get final product.
Embodiment 3
A. raw material forms: 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, operations in the steps below in above-mentioned A:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, adding with the medical material weight ratio is that 12 times of amounts, pH are after 5.0 sour water soaks 40min, heating and refluxing extraction 1 time, each 2h, merging filtrate and to be condensed into relative density be that 1.2 clear paste is standby;
(2) get Radix Scutellariae and Radix Asteris medical material, adding with the medical material weight ratio is after 10 times of amounts, concentration are 50% soak with ethanol 20min, reflux, extract, 2 times, and each 1.5h filters, the merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.2 clear paste is standby;
(3) Folium Eriobotryae and Radix Glycyrrhizae to add together with the medical material weight ratio be 6 times of water gagings, decoct to extract 2 times each 1.5h, filter, after merging filtrate and suitable concentrating, add ethanol to make and contain the alcohol amount to 80%, standing 32h filters, filtrate recycling ethanol and to be condensed into relative density be that 1.2 clear paste is standby;
(4) make 10% Mentholum solution with 95% dissolve with ethanol Mentholum after, using with the medical material weight ratio is the beta-cyclodextrin inclusion compound of 6 times of amounts, gets the Mentholum Benexate Hydrochloride standby;
(5) be after heating in 0.2: 1.0: 1.0 is swelled into glue, to add with glycerol, gelatin and water gross weight than being 3% titanium dioxide, 2% benzoic acid by weight with glycerol, gelatin and water, degasification is made rubber standby;
(6) clear paste described in (1), (2) and (3) mixed and be dried to dried cream powder after, with the Mentholum Benexate Hydrochloride mix homogeneously described in (4), add appropriate Macrogol 2000, aluminum monostearate to stir evenly to get capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5), compacting, and get final product.
Embodiment 4
A. raw material forms: 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, operations in the steps below in above-mentioned A:
(1) with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, adding with the medical material weight ratio is that 10 times of amounts, pH are after 5.0 sour water soaks 40min, heating and refluxing extraction 1 time, each 2h, merging filtrate and to be condensed into relative density be that 1.0 clear paste is standby;
(2) get Radix Scutellariae and Radix Asteris medical material, adding with the medical material weight ratio is after 10 times of amounts, concentration are 50% soak with ethanol 20min, reflux, extract, 2 times, and each 1.5h filters, the merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.0 clear paste is standby;
(3) Folium Eriobotryae and Radix Glycyrrhizae to add together with the medical material weight ratio be 6 times of water gagings, decoct to extract 2 times each 1.5h, filter, after merging filtrate and suitable concentrating, add ethanol to make and contain the alcohol amount to 80%, standing 32h filters, filtrate recycling ethanol and to be condensed into relative density be that 1.0 clear paste is standby;
(4) make 10% Mentholum solution with 95% dissolve with ethanol Mentholum after, using with the medical material weight ratio is the beta-cyclodextrin inclusion compound of 6 times of amounts, gets the Mentholum Benexate Hydrochloride standby;
(5) be after 0.6: 1.0: 1.2 heating and melting becomes glue by weight with glycerol, gelatin and water, add with glycerol, gelatin and water gross weight than being 3% zinc oxide, 2% benzoic acid, degasification is made rubber standby;
(6) clear paste described in (1), (2) and (3) mixed and be dried to dried cream powder after, with the Mentholum Benexate Hydrochloride mix homogeneously described in (4), add appropriate Macrogol 4000, propylene glycol to stir evenly to get capsule liquid, the rubber that makes in capsule liquid and above-mentioned (5), compacting, and get final product.
The mixture that zinc oxide in above-mentioned technique can titanium dioxide proportionings different from zinc oxide 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, potassium sorbate replaces; Macrogol 4000 can replace with acceptable vegetable oil on other polyethylene glycols or pharmaceutics; Propylene glycol can be used in Cera Flava, lecithin, aluminum monostearate, propylene glycol two kinds or two or more, and the mixture that forms by different proportionings replaces.
Claims (8)
1. Chinese medicine preparation for the treatment of cough is characterized in that it is to be prepared from by following technique:
A. raw material forms: 100 parts, 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, Radix Glycyrrhizae, 0.3 part of Mentholum;
B. preparation technology: with 8 flavor raw material of Chinese medicine, operations in the steps below in above-mentioned A:
⑴ with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, adding with the medical material weight ratio is after 8～12 times of amounts, pH are 3.0～benzothiophene acid water soaking, 20～40min, heating and refluxing extraction 1～3 time, it is that 1.0～1.2 clear paste is standby that each 0.5h～2h, extracting solution are condensed into relative density;
⑵ with Radix Scutellariae and Radix Asteris medical material, adding with the medical material weight ratio is after 6～10 times of amounts, concentration are soak with ethanol 20～40min of 50%～90%, reflux, extract, 2～3 times, each 1h～2h is condensed into relative density and is 1.0～1.2 clear paste standby after the extracting solution decompression recycling ethanol;
⑶ it is 6～10 times of water gagings that Folium Eriobotryae and Radix Glycyrrhizae add with the medical material weight ratio together, decoct and extract 2～3 times, each 1h～2h, adding ethanol after extracting solution is suitably concentrated makes and contains the alcohol amount to 60%～80%, standing 24～48h, filter filtrate recycling ethanol and to be condensed into relative density be that 1.0～1.2 clear paste is standby;
⑷ make 2%～10% Mentholum solution with 95% dissolve with ethanol Mentholum after, using with the medical material weight ratio is the beta-cyclodextrin inclusion compound that 2-6 doubly measures, and gets the Mentholum Benexate Hydrochloride standby;
⑸ be after 0.2～1.0:1.0:1.0～1.8 heating is swelled into glue by weight with glycerol, gelatin and water, add with glycerol, gelatin and water gross weight and reach with glycerol, gelatin and water gross weight than the antiseptic that is 2%～6% than the opacifier that is 1%～3%, degasification is made rubber standby;
⑹ after mix the clear paste described in ⑴, ⑵ and ⑶ and be dried to dried cream powder, with the Mentholum Benexate Hydrochloride mix homogeneously described in ⑷, and after adding dispersant, suspending agent to stir evenly capsule liquid, the rubber that makes in capsule liquid and above-mentioned ⑸ is suppressed, and be get final product.
2. a kind of Chinese medicine preparation for the treatment of cough as claimed in claim 1 is characterized in that it is to be prepared from by following technique:
⑴ with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, and adding with the medical material weight ratio is that 10 times of amounts, pH are after 4.0 sour water soaks 30min, heating and refluxing extraction 2 times, each 1h, merging filtrate and to be condensed into relative density be that 1.1 clear paste is standby;
⑵ get Radix Scutellariae and Radix Asteris medical material, and adding with the medical material weight ratio is after 8 times of amounts, concentration are 70% soak with ethanol 30min, reflux, extract, 2 times, and each 1h filters, the merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.1 clear paste is standby;
⑶ it is 8 times of water gagings that Folium Eriobotryae and Radix Glycyrrhizae add with the medical material weight ratio together, decocts to extract 2 times, each 1h, filter, after merging filtrate and suitable concentrating, add ethanol to make and contain the alcohol amount to 70%, standing 24h filters, filtrate recycling ethanol and to be condensed into relative density be that 1.1 clear paste is standby;
⑷ make 5% Mentholum solution with 95% dissolve with ethanol Mentholum after, using with the medical material weight ratio is the beta-cyclodextrin inclusion compound of 3 times of amounts, gets the Mentholum Benexate Hydrochloride standby;
With glycerol, gelatin and water by weight heat for 0.5:1.0:1.2 be swelled into glue after, add with glycerol, gelatin and water gross weight than being 2% opacifier, 5% antiseptic, degasification is made rubber standby;
⑹ after mix the clear paste described in ⑴, ⑵ and ⑶ and be dried to dried cream powder, with the Mentholum Benexate Hydrochloride mix homogeneously described in ⑷, and after adding dispersant, suspending agent to stir evenly capsule liquid, the rubber that makes in capsule liquid and above-mentioned ⑸ is suppressed, and be get final product.
3. a kind of preparation method for the treatment of the Chinese medicine preparation of cough as claimed in claim 1 is characterized in that:
A. raw material forms: 100 parts, 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, Radix Glycyrrhizae, 0.3 part of Mentholum;
B. with 8 flavor raw material of Chinese medicine, operations in the steps below in above-mentioned A:
⑴ with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, adding with the medical material weight ratio is after 8～12 times of amounts, pH are 3.0～benzothiophene acid water soaking, 20～40min, heating and refluxing extraction 1～3 time, it is that 1.0～1.2 clear paste is standby that each 0.5h～2h, extracting solution are condensed into relative density;
⑵ with Radix Scutellariae and Radix Asteris medical material, adding with the medical material weight ratio is after 6～10 times of amounts, concentration are soak with ethanol 20～40min of 50%～90%, reflux, extract, 2～3 times, each 1h～2h is condensed into relative density and is 1.0～1.2 clear paste standby after the extracting solution decompression recycling ethanol;
⑶ it is 6～10 times of water gagings that Folium Eriobotryae and Radix Glycyrrhizae add with the medical material weight ratio together, decoct and extract 2～3 times, each 1h～2h, adding ethanol after extracting solution is suitably concentrated makes and contains the alcohol amount to 60%～80%, standing 24～48h, filter filtrate recycling ethanol and to be condensed into relative density be that 1.0～1.2 clear paste is standby;
⑷ make 2%～10% Mentholum solution with 95% dissolve with ethanol Mentholum after, using with the medical material weight ratio is the beta-cyclodextrin inclusion compound that 2-6 doubly measures, and gets the Mentholum Benexate Hydrochloride standby;
⑸ be after 0.2～1.0:1.0:1.0～1.8 heating is swelled into glue by weight with glycerol, gelatin and water, add with glycerol, gelatin and water gross weight and reach with glycerol, gelatin and water gross weight than the antiseptic that is 2%～6% than the opacifier that is 1%～3%, degasification is made rubber standby;
⑹ after mix the clear paste described in ⑴, ⑵ and ⑶ and be dried to dried cream powder, with the Mentholum Benexate Hydrochloride mix homogeneously described in ⑷, and after adding dispersant, suspending agent to stir evenly capsule liquid, the rubber that makes in capsule liquid and above-mentioned ⑸ is suppressed, and be get final product.
4. the preparation method of the Chinese medicine preparation for the treatment of as claimed in claim 3 cough is characterized in that opacifier selects one or both the mixture in titanium dioxide, zinc oxide.
5. the preparation method of the Chinese medicine preparation for the treatment of as claimed in claim 3 cough is characterized in that antiseptic selects one or more the mixture in benzoic acid, sodium benzoate, ethyl hydroxybenzoate, sorbic acid, potassium sorbate.
6. the preparation method of the Chinese medicine preparation for the treatment of as claimed in claim 3 cough is characterized in that dispersant selects Polyethylene Glycol or vegetable oil.
7. the preparation method of the Chinese medicine preparation for the treatment of as claimed in claim 3 cough is characterized in that suspending agent selects one or more the mixture in Cera Flava, lecithin, aluminum monostearate, propylene glycol.
8. a kind of preparation method for the treatment of the Chinese medicine preparation of cough as claimed in claim 3 is characterized in that:
⑴ with Bulbus Fritillariae Cirrhosae, Herba Ephedrae and Pericarpium Papaveris, and adding with the medical material weight ratio is that 10 times of amounts, pH are after 4.0 sour water soaks 30min, heating and refluxing extraction 2 times, each 1h, merging filtrate and to be condensed into relative density be that 1.1 clear paste is standby;
⑵ get Radix Scutellariae and Radix Asteris medical material, and adding with the medical material weight ratio is after 8 times of amounts, concentration are 70% soak with ethanol 30min, reflux, extract, 2 times, and each 1h filters, the merging filtrate decompression recycling ethanol, and to be condensed into relative density be that 1.1 clear paste is standby;
⑶ it is 8 times of water gagings that Folium Eriobotryae and Radix Glycyrrhizae add with the medical material weight ratio together, decocts to extract 2 times, each 1h, filter, after merging filtrate and suitable concentrating, add ethanol to make and contain the alcohol amount to 70%, standing 24h filters, filtrate recycling ethanol and to be condensed into relative density be that 1.1 clear paste is standby;
⑷ make 5% Mentholum solution with 95% dissolve with ethanol Mentholum after, using with the medical material weight ratio is the beta-cyclodextrin inclusion compound of 3 times of amounts, gets the Mentholum Benexate Hydrochloride standby;
With glycerol, gelatin and water by weight heat for 0.5:1.0:1.2 be swelled into glue after, add with glycerol, gelatin and water gross weight than being 2% titanium dioxide, 5% benzoic acid, degasification is made rubber standby;
⑹ after mix the clear paste described in ⑴, ⑵ and ⑶ and be dried to dried cream powder, with the Mentholum Benexate Hydrochloride mix homogeneously described in ⑷, add appropriate soybean oil, lecithin to stir evenly to get capsule liquid, the rubber that makes in capsule liquid and above-mentioned ⑸, compacting, and get final product.
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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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Effective date of registration: 20121130 Address after: 710119, No. 70, West Avenue, new industrial zone, Changan District hi tech Development Zone, Shaanxi, Xi'an Applicant after: Shaanxi Buchang Hi-Tech Pharmaceutical Co.,Ltd. Address before: 712000 Xianyang city of Shaanxi province qindouou Weiyang Road West No. 123 Applicant before: Shaanxi Buchang Pharmaceuticals Co.,Ltd. |
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Effective date of registration: 20240515 Address after: No. 16 Buchang Road, Qindu District, Xianyang City, Shaanxi Province, 712023 Patentee after: Shaanxi Buchang Pharmaceuticals Co.,Ltd. Country or region after: China Address before: 710119 No.70, West Avenue, new industrial park, high tech Development Zone, Chang'an District, Xi'an City, Shaanxi Province Patentee before: Shaanxi Buchang Hi-Tech Pharmaceutical Co.,Ltd. Country or region before: China |
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