CN103446284A - Traditional Chinese medicine compound granules for treating infantile asthma and preparation method thereof - Google Patents
Traditional Chinese medicine compound granules for treating infantile asthma and preparation method thereof Download PDFInfo
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Abstract
The invention provides traditional Chinese medicine compound granules for treating infantile asthma and a preparation method thereof. Decoction for purging lung and relieving asthma is made into the granules by applying modern science and technology in combination with clinical requirements and medicine natures according to the application status of the decoction for purging lung and relieving asthma, which is clinically proven recipe. The preparation method comprises the extraction of effective ingredients and the preparation of the granules. The preparation technology comprises an extraction process, a concentration process, a purification process and a forming process. Compared with conventional decoction, the granules prepared by the technology have the advantages that the main effective ingredients of the decoction are retained, the appearance, the granularity, the moisture, the solubility and the like of the granules reach pharmacopeia requirements, the quality of the granules is stable in comparison with the quality of liquid preparations such as oral liquid and mixtures, the dosage is little, the granules are convenient to transport and carry and have good mouth feel, the children compliance is improved, and after being brewed, the granules have good mouth feel by using a flavoring agent for changing the mouth feel and are easy to accept by children and the like. Meanwhile, the production method can be used for realizing industrial production and mechanical packaging technically. Therefore, the decoction for purging lung and relieving asthma is modified into the granules with relatively good application prospect.
Description
Technical field
The invention belongs to the pharmacy of Chinese materia medica technical field, be specifically related to a kind of dosage form for the treatment of the infantile asthma clinical proved recipe and change and preparation method thereof.
Background technology
The eliminating pathogen from the lung for relieving asthma spirit is as the proved recipe of a determined curative effect, with the form of decoction, is applied to clinical.Decoction claims again soup, refers to herbal decoction piece with decocting or soaking the liquid dosage form that the method for the extracting juice that removes slag is made.Below summed up the drawback existed in the decoction use procedure.
1. due to the restriction of solvent.Some is fat-soluble and the slightly solubility composition is fried not exclusively.For example Ore class, shell, Class A, angle medicine, just have these phenomenons.Gypsum Fibrosum, Carapax Et Plastrum Testudinis, Concha Margaritifera etc., need to smash during decoction and be decocted first about 30 minutes; Some toxic medicament, as Aconitum carmichjaelii Debx., Radix Aconiti Lateralis Preparata etc., also need to be decocted first 1～2 hour in order to alleviate its toxic action, and when using this class Chinese medicine, decoction process will extend, and increase trouble.The liposoluble constituent tanshinone of side's Chinese crude drug Radix Salviae Miltiorrhizae can improve blood circulation, antibiotic and antiinflammatory, and the science theory of " asthma should invigorate blood circulation purging FU-organs " proposed with professor Han Xinmin is agreed with mutually; Semen Armeniacae Amarum adopts ethanol to do the stripping that solvent can increase the effective ingredient amygdaloside; And Semen Sinapis Albae adopts ethanol to do solvent can to reduce the myrosase activity, reduce the generation of sulfide, thereby reduce toxicity.
2. oral dose is large, bitter in the mouth, and the child more is difficult under clothes.From the clinical application situation, it is about 500ml that general one secondary Chinese medicine finally decocts the gained amount of liquid medicine, if for calculus class patient, requires the last decocting liquid amount can be more; And most of Chinese medicine taste hardship, the child is difficult for accepting, and we are children, and in use child's compliance seems even more important.
3. use inconvenient.Modern life day is becoming tight, the secondary Chinese medicine decocting of patient seldom free one 2～3 times, now boil existing clothes, just so, many institutes of traditional Chinese medicine release for the business of decocting Chinese medicine, even can solve the part sufferer difficult problem of boiling medicine, but still exist the decoction volume large, carry inconvenience, need to often go the problem such as hospital.
So proved recipe eliminating pathogen from the lung for relieving asthma spirit is developed to, a kind of mouthfeel is good, drug compliance strong, it is easy to carry to transport, and the dosage form that is particularly useful for children taking is to need the problem of solution in prior art badly.
Summary of the invention
The present invention is directed to the application present situation of this clinical proved recipe of eliminating pathogen from the lung for relieving asthma spirit, in conjunction with clinical needs and pharmaceutical properties, use modern science and technology to be made into granule, it has retained decoction and has absorbed fast, onset characteristics rapidly, make to transport easy to carry, after changing mouthfeel by correctives, child's compliance is improved simultaneously, and quality is stable than liquid preparations such as oral liquid, mixture, technique can realize suitability for industrialized production and mechanical packaging.The present invention simultaneously also provides the preparation technology of the Chinese native medicine compound prescription pellet of this treatment infantile asthma, has mainly comprised extraction process, concentration technology, process for refining, moulding process.
The invention provides a kind of preparation method for the treatment of the Chinese native medicine compound prescription pellet of infantile asthma: comprise that alcohol extraction, water extraction, alcohol extract concentrate, water extraction liquid is concentrated, six steps are made with extra care, granulated to water extracting liquid, concrete preparation technology is as follows:
(1) alcohol extraction: get Semen Armeniacae Amarum, Radix Salviae Miltiorrhizae, Semen Sinapis Albae mixture, add 85% ethanol of 8 times of amounts, heating and refluxing extraction 3 times, each 0.5 hour, obtain alcohol extract;
(2) water extraction: after getting alcohol extraction, medicinal residues add Herba Ephedrae, Radix Et Rhizoma Rhei, Semen Lepidii (Semen Descurainiae), Radix Glycyrrhizae, Pericarpium Trichosanthis, Rhizoma Polygoni Cuspidati to carry out water extraction, add the water soaking of 12 times after 35 minutes, heating and refluxing extraction 3 times, each 1.5 hours, second and third time adds 10 times of water gagings before extracting again, obtains water extraction liquid;
(3) alcohol extract is concentrated: gained alcohol extract in step (1) is heated to 70 ℃ of concentrating under reduced pressure under vacuum 0～0.08Mpa, obtains the alcohol extraction concentrated solution;
(4) water extraction liquid is concentrated: gained water extraction liquid in step (2) is heated to 80 ℃ under vacuum 0～0.08Mpa and is evaporated to and obtains water extracting liquid, the thick paste that to can be relative density be 1.07 or medicinal liquid are than being the concentrated solution of 1:5;
(5) water extracting liquid is refining: adopt gained water extracting liquid in step (4) alcohol deposition method to make with extra care purification and obtain the concentrated thick paste of water extraction: if water extracting liquid is the thick paste that relative density is 1.07, add 95% ethanol, after alcohol is sink to the rear standing 12h of concentration 50%, filter concentrating under reduced pressure; If water extracting liquid is medicinal liquid than being the concentrated solution of 1:5, use natural clarifying agent ZTC II 1+1 to be made with extra care, add 8% B component solution under 70 ℃, stir 10min, then stir 1 time every 30min, stir and add the 4%A component solution under 50 ℃ after 2h, after insulation 30min, stir again, standing 2h is centrifugal, filter concentrating under reduced pressure;
(6) granulate: after gained alcohol extraction concentrated solution in step (3) and the concentrated thick paste of step (5) water extraction are mixed homogeneously in the 3:1 ratio with dextrin, in 75 ℃ of drying under reduced pressure, pulverize, obtain intermediate medicated powder, get intermediate medicated powder and add starch: the mixed accessories of mannitol=2:3 mixes, add 0.3% protein sugar, 1.0% citric acid, with 12～14% water granule processed, 60 ℃ of dryings, packing, every bag of 8 grams.
The concrete technology flow process is shown in Fig. 1.
The present invention provides a kind of Chinese native medicine compound prescription pellet for the treatment of infantile asthma simultaneously, by following medical material, is made: Semen Armeniacae Amarum, Radix Salviae Miltiorrhizae, Semen Sinapis Albae, Herba Ephedrae, Radix Et Rhizoma Rhei, Semen Lepidii (Semen Descurainiae), Radix Glycyrrhizae, Pericarpium Trichosanthis, Rhizoma Polygoni Cuspidati prepare gained by above-mentioned preparation method.
Beneficial effect
The Chinese native medicine compound prescription pellet for the treatment of infantile asthma provided by the invention, it is for to change system into granule by clinical proved recipe eliminating pathogen from the lung for relieving asthma spirit, and this granule has following advantage compared to traditional decoction:
1. retained the main effective ingredient of decoction, the granule indices reaches requirement and steady quality: index composition ephedrine hydrochloride be in medical material content 52.17%; Herba Ephedrae, Pericarpium Trichosanthis, Radix Salviae Miltiorrhizae, Rhizoma Polygoni Cuspidati, Radix Et Rhizoma Rhei and Radix Glycyrrhizae all can detect by thin layer chromatography in prepared granule; The mode of appearance of granule, granularity, moisture, dissolubility etc. all reach the pharmacopeia requirement; Quality is stable than liquid preparations such as oral liquid, mixture;
2. dose is few and transport easy to carry: every bag of 8g of granule dosage, and dose is few and be easy to carry about with one;
3. mouthfeel is good, and child's compliance improves: after changing mouthfeel by correctives, it is good that granule brews rear mouthfeel, and the child easily accepts.
The preparation method of the Chinese native medicine compound prescription pellet for the treatment of infantile asthma provided by the invention, its technique can realize suitability for industrialized production and mechanical packaging.Therefore, by the eliminating pathogen from the lung for relieving asthma spirit, from the decoction improvement, be granule, there is application prospect preferably.
The accompanying drawing explanation
The process chart of Fig. 1 preparation method of the present invention.
The relation of Fig. 2 medical material water suction volume and soak time;
Wherein, the volume V/ medical material weight * 100%=200% of water absorption rate=water suction.
The moisture absorption percentage rate (%) of Fig. 3 different auxiliary material.
The specific embodiment
Further illustrating technical solution of the present invention below in conjunction with specific embodiment, is not the restriction to the technical program.
The research of the preparation method of the Chinese native medicine compound prescription pellet of embodiment 1 treatment infantile asthma
This product is according to the character of prescription Chinese medicine, it is divided into to alcohol extraction part and water extraction part, and to take amygdaloside and ephedrine hydrochloride be the index composition, the concentration of alcohol of extraction time, extraction time, solvent load, alcohol extraction part of take is the investigation factor, and it has been carried out to three horizontal quadratures tests of each factor; Investigate different method for concentration and thickening temperature, the selected concentrated condition be applicable to; Index composition ephedrine hydrochloride retention rate and the impurities removing efficiency of three kinds of process for purification of contrast, screening is applicable to process for purification and the purification condition of this product; Use proportioning to the kind of the kind of adjuvant and consumption, wetting agent and consumption, two kinds of correctivess is investigated, take obtain making easily, granule that appearance characteristics is good screened as standard.
Concrete preparation method step is as follows:
(1) alcohol extraction: get Semen Armeniacae Amarum, Radix Salviae Miltiorrhizae, Semen Sinapis Albae mixture, add 85% ethanol of 8 times of amounts, heating and refluxing extraction 3 times, each 0.5 hour, obtain alcohol extract;
(2) water extraction: after getting alcohol extraction, medicinal residues add Herba Ephedrae, Radix Et Rhizoma Rhei, Semen Lepidii (Semen Descurainiae), Radix Glycyrrhizae, Pericarpium Trichosanthis, Rhizoma Polygoni Cuspidati to carry out water extraction, add the water soaking of 12 times after 35 minutes, heating and refluxing extraction 3 times, each 1.5 hours, second and third time adds 10 times of water gagings before extracting again, obtains water extraction liquid;
(3) alcohol extract is concentrated: gained alcohol extract in step (1) is heated to 70 ℃ of concentrating under reduced pressure under vacuum 0～0.08Mpa, obtains the alcohol extraction concentrated solution;
(4) water extraction liquid is concentrated: gained water extraction liquid in step (2) is heated to 80 ℃ under vacuum 0～0.08Mpa and is evaporated to and obtains water extracting liquid, the thick paste that to can be relative density be 1.07 or medicinal liquid are than being the concentrated solution of 1:5;
(5) water extracting liquid is refining: adopt gained water extracting liquid in step (4) alcohol deposition method to make with extra care purification and obtain the concentrated thick paste of water extraction: if water extracting liquid is the thick paste that relative density is 1.07, add 95% ethanol, after alcohol is sink to the rear standing 12h of concentration 50%, filter concentrating under reduced pressure; If water extracting liquid is medicinal liquid than being the concentrated solution of 1:5, use natural clarifying agent ZTC II 1+1 to be made with extra care, add 8% B component solution under 70 ℃, stir 10min, then stir 1 time every 30min, stir and add the 4%A component solution under 50 ℃ after 2h, after insulation 30min, stir again, standing 2h is centrifugal, filter concentrating under reduced pressure;
(6) granulate: after gained alcohol extraction concentrated solution in step (3) and the concentrated thick paste of step (5) water extraction are mixed homogeneously in the 3:1 ratio with dextrin, in 75 ℃ of drying under reduced pressure, pulverize, obtain intermediate medicated powder, get intermediate medicated powder and add starch: the mixed accessories of mannitol=2:3 mixes, add 0.3% protein sugar, 1.0% citric acid, with 12～14% water granule processed, 60 ℃ of dryings, packing, every bag of 8 grams.
The Semen Armeniacae Amarum of embodiment 2 Study on extraction, Radix Salviae Miltiorrhizae, Semen Sinapis Albae three flavor pharmaceutical decocting piece alcohol extraction processes
1, orthogonal test
Physicochemical property and pharmacological property according to this three flavors Chinese medicine, adopt alcohol extracting method to be extracted, and take amygdaloside and yield of extract as index, adopt orthogonal test to investigate concentration of alcohol, the ethanol consumption, extraction time, the influence degree of the influence factors such as extraction time to two indexs.Concrete experimental design and the results are shown in Table 1～5.
Table 1 alcohol extraction process orthogonal test factor level table
Table 2 orthogonal and experimental result (on the impact of amygdaloside content)
The variance analysis of table 3 amygdaloside content
From the results of analysis of variance, the F value of extraction time is greater than 19 and is less than 99, content to amygdaloside has a significant impact, and the F value of alcohol adding amount, determining alcohol and extraction time all is less than 19, illustrate that these three influence factors are less to the amygdaloside content influence, D>B>A>C, the optimum extraction process that the amygdaloside of take is index is A
1b
1c
1d
3, 85% of 12 times of amounts alcohol heating reflux extracts 3 times, each 1.5h.
Table 4 orthogonal and experimental result (on the impact of yield of extract)
The variance analysis of table 5 yield of extract
From the intuitive analysis the results of analysis of variance, extraction time has utmost point appreciable impact to yield of extract, and also there are appreciable impact determining alcohol and extraction time, and add alcohol, doubly amount is less on the yield of extract impact, D > A > C > B.The optimum extraction process that the yield of extract of take is index is A
3b
2c
1d
3, the alcohol heating reflux of 10 times 65% extracts 3 times, each 1.5h.
Analysis-by-synthesis: because the alcohol extraction medicinal residues will add water extraction, in guaranteeing when amygdaloside is extracted most to make medical material, the unknown or indefinite effective ingredient are extracted fully, therefore select 85% ethanol; Owing to adding pure multiple to there are no significant the impact of two kinds of index compositions, according to needs of production, be to save cost, shorten concentration time, therefore select the ethanol extraction of 8 times of amounts; Although there is considerable influence extraction time to yield of extract, little to the content influence of amygdaloside, for cost-saving, reduce heat time heating time, select each 0.5h of extraction.Finally definite extraction process is A
1b
3c
3d
3, both having added 85% ethanol is 8 times of amounts of medical material weight, extracts 3 times, each 0.5h.
2, assay method
Chromatographic condition chromatographic column: Hedera C18 (4.6mm * 250mm, 0.5 μ m); Mobile phase: methanol-water (23:77); Flow velocity: 0.9mL/min, column temperature: 30 ℃; Detect wavelength: 207nm; Sample size: 10 μ L.
It is appropriate that the preparation of reference substance solution takes the amygdaloside reference substance, and accurately weighed being placed in volumetric flask adds methanol and make the reference substance solution of every lmL containing 320 μ g, and concentration is 0.32mg/mL.
Need testing solution preparation takes totally nine parts of Semen Armeniacae Amarums, Radix Salviae Miltiorrhizae, Semen Sinapis Albae three flavor medical material in the original prescription ratio, by the Orthogonal Experiment and Design table, extracted respectively, filtrate is taken advantage of heat filtering, be settled to 1000mL after cooling, the medicinal liquid taken a morsel after standardize solution is crossed the filtering with microporous membrane of 0.45 μ m, as need testing solution.Difference injection liquid chromatography, every part of 10 μ L, record the amygdaloside peak area, calculates its content.
Yield of extract is measured precision and is measured each tested number sample extracting solution 20ml that oneself is settled to the 1000ml volumetric flask, puts in the evaporating dish that is dried to constant weight, after water bath method, dry 3h in 105 ℃ of baking ovens, cooling 30min in exsiccator is put in taking-up, and precise weighing, calculate yield of extraction rapidly.
3, quadrature confirmatory experiment
Press recipe quantity, get each 3 parts of alcohol extraction medicines, according to Optimization Technology A
1b
3c
3d
3, both measured 85% ethanol extraction 3 times for 8 times, each 0.5h, merging filtrate, filter, and filtrate is settled to 1000ml, carries out assay and the yield of extract of amygdaloside and measures.The results are shown in Table 6.
Table 6 alcohol extraction quadrature demonstration test
By the technique of having optimized, extracted as seen, each index content is higher and basically identical, shows that this alcohol extraction process guarantees that index content has guaranteed again stability.
The extraction process by water of the Herba Ephedrae of embodiment 3 Study on extraction, Radix Et Rhizoma Rhei, Semen Lepidii (Semen Descurainiae), Radix Glycyrrhizae, Pericarpium Trichosanthis, Rhizoma Polygoni Cuspidati flavor 6 flavor Chinese medicines and alcohol extraction medicinal residues
1, orthogonal test factor level table
Alcohol extraction medicinal residues and Herba Ephedrae etc. are closed and decoct, can embody the characteristics that the Chinese medicine compound traditional decoction is decocted altogether, make the aqueous soluble active constituent in whole side be able to abundant proposition.Take Determination of ephedrine hydrochloride, total anthraquinones content and yield of extract as index, carry out L
9(3
4) orthogonal test, three principal elements that affect extraction process by water are carried out preferably, and determine these three influence factors' level on the basis of document.
Table 7 extraction process by water orthogonal test factor level table
2, the mensuration of water absorption rate
This effects the absorbent time of square Chinese crude drug and the relation of water absorption, draw needed time when medical material reaches maximum water absorption.Get the about 25g of above-mentioned dried alcohol extraction medicinal residues, Herba Ephedrae 5g, Semen Lepidii (Semen Descurainiae) 10g, Pericarpium Trichosanthis 10g, Rhizoma Polygoni Cuspidati 12g, Radix Et Rhizoma Rhei 3g, Radix Glycyrrhizae 3g, 68g altogether.Add 10 times of water gagings and soak, observe once every 5min.
Result shows as Fig. 2, and after 35min, all medical materials soak into substantially, and the water absorption of all medical materials is 2 times of own medical material weight, so, when medical material extracts for the first time, amount of water will be taken water absorption rate into account, and first soaks at least 35min before medical material decocts.
3, yield of extract is measured
Accurate amount quadrature sample liquid 20mL is placed in respectively the evaporating dish of constant weight, water bath method, and residue, in 105 ℃ of dry 3h, takes out, and puts in exsiccator and places 30min, weighs, and calculates yield of extract.
4, orthogonal experiment and result
Table 9 water extraction orthogonal test and result
Table 10 the results of analysis of variance
Analysis result: affect in three factors of water extraction effect, extraction time (C) has the greatest impact to three index compositions, and has the significance impact, therefore extraction time is selected 3 times; Extraction time, (B) only took second place, but impact is not remarkable, and 2 levels and 3 levels are very approaching, therefore extraction time selection 1h; Amount of water (A) impact is minimum, is to reduce concentration time, selects 10 times of amount of water.Do not consider actual production, optimum combination is A
3b
3c
3, add 12 times of water gagings and extract 3 times, each 1.5h.In line with the principle of energy efficiency, determine that the water conservancy project skill of eliminating pathogen from the lung for relieving asthma spirit granule is: A
2b
2c
3, extract and add 12 times of water gagings for the first time, rear 10 times of water gagings (considering the medical material water absorption), totally 3 times, the each 1h of adding for twice.
5, quadrature confirmatory experiment
Take the medical materials such as Herba Ephedrae, Pericarpium Trichosanthis, Semen Descurainiae (parched) in the prescription ratio, tested by above-mentioned preferred processing condition respectively, merge water extraction liquid, filter, record filtrate volume after cooling.Respectively index components is measured.
Table 11 demonstration test result
From table 11, the extraction process A that we are definite
2b
2c
3than orthogonal test optimum process A
3b
3c
3, being more or less the same of the yield of three index components, illustrate that definite technique is reasonable, more is conducive to save cost.
Embodiment 4 concentration technology researchs
Different concentration technologies is larger on the impact of the effective ingredient in medicinal liquid, now take amygdaloside as detecting index, investigate the impact of the temperature of concentrating under reduced pressure on active ingredient in alcohol extract, take ephedrine hydrochloride as detecting index, investigate the uncovered concentrated impact on effective ingredient in water extraction liquid of concentrating under reduced pressure temperature and room temperature, optimize best concentration technology, to guarantee the content of effective ingredient.
1, the thickening temperature of alcohol extract is investigated
The medical material of getting 3 times of recipe quantities is with 8 times of amount 85% ethanol extractions 3 times, each 0.5h, filter cooling after, be settled to 3000mL, get alcohol extract 700mL for every part, totally 4 parts, carry out respectively 65～80 ℃ of concentrating under reduced pressure 25min under vacuum 0～0.08Mpa.
The impact of table 12 thickening temperature alcohol extract
As seen from the above table, the concentrating under reduced pressure temperature has obvious impact to the content of amygdaloside in ethanol extract, especially when temperature rises to 75～80 ℃, amygdaloside content obviously reduces, and 65～70 ℃ of time impacts are less and be more or less the same, due to the concentrated speed of 70 ℃, therefore select 70 ℃ for the concentrating under reduced pressure temperature of alcohol extract.
2, the concentrated mode of water extraction liquid is investigated
The medical material of getting 6 times of recipe quantities adds 10 times of water gagings and decocts 3 times, each 1h, filter cooling after, record volume, get totally 5 parts of the water extraction liquid of every part of 1000mL, carry out respectively concentrating under reduced pressure 1h and the uncovered concentrated 1h of room temperature of 70～85 ℃ of vacuum 0～0.08Mpa.
The impact on water extraction liquid of the different thickening temperatures of table 13 and mode
As seen from the above table, concentrating under reduced pressure is less on the Determination of ephedrine hydrochloride impact, and room temperature is uncovered concentrated bigger on the Determination of ephedrine hydrochloride impact, so select the concentrated mode of concentrating under reduced pressure as water extract, in the temperature of 70～85 ℃ of four kinds of concentrating under reduced pressure, 70～75 ℃ of speed are slower, and 80～85 ℃ of speed are fast, during due to 85 ℃ of concentrating under reduced pressure of selection, medicinal liquid is unstable, easily boiling ejection, finally select active substance to retain more, concentrated speed faster 80 ℃ be the concentrating under reduced pressure temperature.
Embodiment 5 process for refining researchs
In order to reduce the dose of preparation, water extraction is partly carried out to purification and impurity removal technique.Take the content of ephedrine hydrochloride and dry extract yield in preliminary experiment has compared precipitate with ethanol, the ZTC II 1+1 sedimentation method, three kinds of process for purification of the chitosan sedimentation method as investigating index, find that the chitosan sedimentation method have considerable influence to the index composition, finally select alcohol deposition method and the ZTC II 1+1 sedimentation method exquisite method as this granule, and drawn best alcohol precipitation process by orthogonal test.
1, alcohol deposition method
(1) factor level selective basis pertinent literature and preliminary experiment result, the factor of finding affect the precipitate with ethanol effect mainly contains concentration and time of repose after relative density of medicine liquid, precipitate with ethanol, employing L
9(3
4) the preferred best alcohol precipitation process of orthogonal test.
Table 14 alcohol deposition method orthogonal test factor level table
(2) 9 parts of the preparation of test specimen water intaking extracts are concentrated into corresponding relative density, and the ethanol with 95% stirs and is added to corresponding concentration, and the standing corresponding time, centrifugal sucking filtration, obtain filtrate, and standardize solution is in the 100mL measuring bottle.Measure concentrated solution 10mL and measure its dry extract yield.Get above-mentioned solution and cross 0.45 μ m microporous filter membrane, get filtrate appropriate, the injection liquid chromatography is measured the content of ephedrine hydrochloride under above-mentioned chromatographic condition.
(3) alcohol deposition method interpretation of result
Table 15 eliminating pathogen from the lung for relieving asthma spirit granule alcohol precipitation process orthogonal test arranges and result
Table 16 alcohol deposition method analysis of variance table
Test result analysis differential R value from orthogonal test table is known, and the factor size that affects ephedrine hydrochloride and yield of extract is all B successively>A>C>D, the extraction process that Determination of ephedrine hydrochloride is the highest is A
2b
1c
1, the minimum extraction process of yield of extract is A
2b
3c
1; According to variance analysis, A and B two factors all have a significant impact Determination of ephedrine hydrochloride and yield of extract, and C affects without significance, with the top-priority principle of Determination of ephedrine hydrochloride, finally determine that best alcohol precipitation process is A
2b
1c
1, the medicinal liquid alcohol that soon relative density will be 1.07 is sink to the rear standing 12h of concentration 50%.
(4) quadrature demonstration test water intaking extract is pressed best alcohol precipitation process repeated trials 3 times, measures its Determination of ephedrine hydrochloride and yield of extract.The meansigma methods of Determination of ephedrine hydrochloride and yield of extract is 5.266mg/g and 19.06% (n=3).As can be seen here, press its Determination of ephedrine hydrochloride of the refining sample of precipitate with ethanol optimised process and yield of extract basicly stable, illustrate that this process stabilizing is reliable.
Table 17 precipitate with ethanol quadrature demonstration test result
2, the ZTC II 1+1 sedimentation method
(1) the preparation of clarifier solution
1. the preparation precision of A component solution takes 1.0g ZTC II 1+1 clarifier A component, first use appropriate distilled water that the A component is stirred into to pasty state, then adding distil water limit in limit mixes to 100mL, after swelling 24h, stirs, filter with gauze, obtain 1%A component viscose liquid.
2. the preparation precision of B component solution takes 1.0g ZTC II 1+1 clarifier B component, first use appropriate 1% acetum dissolve and stir into pasty state, and then use above-mentioned solution to mix to 100mL, stir after swelling 24h, filter with gauze, obtain 1%B component viscose liquid.
A, B2 component addition sequence be settled medicinal liquid pH really > 4.8, first add the B component, after add the A component; When medicinal liquid pH<4.8, first add the A component, after add the B component.Get eliminating pathogen from the lung for relieving asthma spirit granule water extraction liquid and measure its pH, show that the pH of eliminating pathogen from the lung for relieving asthma spirit granule water extraction liquid is 6.09, higher than 4.8, so first add the B component, after add the A component, the amount ratio of 2 components is B: A=2: 1.
(2) EXPERIMENTAL DESIGN is determined according to preliminary experiment, and liquor strength, AB component solution add fashionable temperature (40～60 ℃), AB amounts of components (4%～12%), time of repose (being greater than 2h), and the factors such as mixing speed are all not obvious on the clarifying effect impact.The accurate medicinal liquid of drawing, than being the medical material water extraction concentrated solution 50mL of 1:5, adds the B component solution of 4mL under 70 ℃, stirs 10min, then every 30min, stirs 1 time, stir and add the 2mLA component solution under 50 ℃ after 2h, stir again standing 2h after insulation 30min, centrifugal, sucking filtration, measurement volumes.Parallelly carry out three parts.
(3) ZTC II 1+1 sedimentation method interpretation of result
Table 18ZTC II 1+1 sedimentation method result of the test
The sedimentation effect of natural clarifying agent is better, also can remove to a certain extent impurity, the composition of remaining valid, and its ephedrine hydrochloride retention rate and impurities removing efficiency, all a little less than alcohol deposition method, also can be used as the process for refining of eliminating pathogen from the lung for relieving asthma spirit granule.
The research of embodiment 6 pelletizing forming techniques
1, the selection of adjuvant
By dextrin, mannitol, lactose, soluble starch, five kinds of adjuvants of xylitol and intermediate medicated powder, cross 60 mesh sieves, 60 ℃ of dry 0.5h, cooling rear precision respectively measures 1.0g, be placed in the flat weighing botle of tool lid, after opening lid, put into the drying tower that fills sodium chloride supersaturation liquid, take out and weigh when 6h, 12h, 24h, 36h, 48h, calculate the moisture absorption percentage rate.
Weight * 100% before moisture absorption percentage rate (%)=(the front weight of weight one moisture absorption after moisture absorption)/moisture absorption
The moisture absorption percentage rate (%) of table 19 different auxiliary material
Demonstration according to above-mentioned result of the test and Fig. 3, carry out analysis-by-synthesis, the not liquescent dextrin of initial option or starch and be difficult for the lactose of moisture absorption or the mannitol collocation is mixed accessories, respectively by two kinds of adjuvants temporarily in 1:1 ratio mix homogeneously, again medicated powder is mixed homogeneously in the ratio of 1:1 with mixed accessories, 60 ℃ of dry 0.5h are placed in above-mentioned drying tower, investigate the 48h hydroscopicity.Show that by test starch and the combination of mannitol can obtain all comparatively suitable dressing that mixes of appearance character and hydroscopicity.
The moisture absorption percentage rate (%) of table 20 mixed accessories
Carry out analysis-by-synthesis according to result of the test, the starch combination that the initial option hydroscopicity is lower, starch and lactose and mannitol collocation reduce the medicated powder Degree of Liquefaction, and because the hydroscopicity of these two kinds of collocation is more or less the same, therefore select not cause that the syndromic mannitol of lactose intolerance mixes the adjuvant as this children preparation with starch.
2, the mixing ratio of two kinds of adjuvants
Starch is mixed homogeneously by different proportion with mannitol, then medicated powder is mixed homogeneously in the ratio of 1:1 respectively with several mixed accessories, 60 ℃ of dry 0.5h are placed in above-mentioned drying tower, investigate the 48h hydroscopicity.
The mixing ratio of table 21 starch and mannitol
Known according to experimental result, the impact of comparing the medicated powder hydroscopicity of starch and mannitol is less, in order to obtain hydroscopicity and dissolution rate preferably, this preparation initial option starch: mannitol=1:1.
3, the Determination of quantity of correctives
The powder of getting it filled, add starch mannitol mixture (1:1) in the 1:1 ratio, adds a certain proportion of protein sugar of suitable total amount and citric acid, gets 5g after mixing and add 50ml warm water, carries out the mouthfeel evaluation after dissolving.
The consumption of table 22 correctives is selected
Finally select 0.3% protein sugar, 1.0% citric acid, mouthfeel is better, moderately sour and sweet.
4, the selection of wetting agent kind and consumption
The powder of getting it filled, add starch mannitol mixture (1:1) in the 1:1 ratio, then add 0.3% protein sugar and 1.0% citric acid, after mix homogeneously, successively adds the second alcohol and water of variable concentrations to carry out moistening, crosses 14 mesh sieve extrusion granulators, 60 ℃ of dryings, granulate.
The screening of table 23 wetting agent
By upper table result, can be found out, take water as the wetting agent granulating efficiency good.
5, supplementary product consumption is selected
The powder of getting it filled, add starch mannitol mixture (1:1) by different proportion, then add 0.3% protein sugar and 1.0% citric acid, after mix homogeneously, adds water to carry out moistening, crosses 14 mesh sieve extrusion granulators, 60 ℃ of dryings, granulate.
Table 24 medicated powder and supplementary product consumption ratio
The auxiliary granule segmentation rate made than 2:3 of medicine is lower as can be seen from the above table, is difficult for sticky frame, and color is better.
6, the selection of wetting agent consumption
The powder of getting it filled, add starch mannitol mixture (1:1) in the 2:3 ratio, then add 0.3% protein sugar and 1.0% citric acid, after mix homogeneously, adds a certain amount of water to carry out moistening, crosses 14 mesh sieve extrusion granulators, 60 ℃ of dryings, granulate.
Table 25 wetting agent consumption is selected
As seen from the above table, the consumption of wetting agent should be controlled between 12% to 14%.
Claims (2)
1. a preparation method for the treatment of the Chinese native medicine compound prescription pellet of infantile asthma, comprise that alcohol extraction, water extraction, alcohol extract concentrate, water extraction liquid is concentrated, six steps are made with extra care, granulated to water extracting liquid, and concrete preparation technology is as follows:
(1) alcohol extraction: get Semen Armeniacae Amarum, Radix Salviae Miltiorrhizae, Semen Sinapis Albae mixture, add 85% ethanol of 8 times of amounts, heating and refluxing extraction 3 times, each 0.5 hour, obtain alcohol extract;
(2) water extraction: after getting alcohol extraction, medicinal residues add Herba Ephedrae, Radix Et Rhizoma Rhei, Semen Lepidii (Semen Descurainiae), Radix Glycyrrhizae, Pericarpium Trichosanthis, Rhizoma Polygoni Cuspidati to carry out water extraction, add the water soaking of 12 times after 35 minutes, heating and refluxing extraction 3 times, each 1.5 hours, second and third time adds 10 times of water gagings before extracting again, obtains water extraction liquid;
(3) alcohol extract is concentrated: gained alcohol extract in step (1) is heated to 70 ℃ of concentrating under reduced pressure under vacuum 0 ~ 0.08Mpa, obtains the alcohol extraction concentrated solution;
(4) water extraction liquid is concentrated: gained water extraction liquid in step (2) is heated to 80 ℃ under vacuum 0 ~ 0.08Mpa and is evaporated to and obtains water extracting liquid, the thick paste that to can be relative density be 1.07 or medicinal liquid are than being the concentrated solution of 1:5;
(5) water extracting liquid is refining: adopt gained water extracting liquid in step (4) alcohol deposition method to make with extra care purification and obtain the concentrated thick paste of water extraction: if water extracting liquid is the thick paste that relative density is 1.07, add 95% ethanol, after alcohol is sink to the rear standing 12h of concentration 50%, filter concentrating under reduced pressure; If water extracting liquid is medicinal liquid than being the concentrated solution of 1:5, use natural clarifying agent ZTC II 1+1 to be made with extra care, add 8% B component solution under 70 ℃, stir 10min, then stir 1 time every 30min, stir and add the 4%A component solution under 50 ℃ after 2h, after insulation 30min, stir again, standing 2h is centrifugal, filter concentrating under reduced pressure;
(6) granulate: after gained alcohol extraction concentrated solution in step (3) and the concentrated thick paste of step (5) water extraction are mixed homogeneously in the 3:1 ratio with dextrin, in 75 ℃ of drying under reduced pressure, pulverize, obtain intermediate medicated powder, get intermediate medicated powder and add starch: the mixed accessories of mannitol=2:3 mixes, add 0.3% protein sugar, 1.0% citric acid, with 12 ~ 14% water granule processed, 60 ℃ of dryings, packing, every bag of 8 grams.
2. the Chinese native medicine compound prescription pellet of the treatment infantile asthma prepared by preparation method described in claim 1 is characterized by by following medical material and makes: Semen Armeniacae Amarum, Radix Salviae Miltiorrhizae, Semen Sinapis Albae, Herba Ephedrae, Radix Et Rhizoma Rhei, Semen Lepidii (Semen Descurainiae), Radix Glycyrrhizae, Pericarpium Trichosanthis, Rhizoma Polygoni Cuspidati are prepared into granule.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104069362A (en) * | 2014-07-02 | 2014-10-01 | 吴新荣 | Preparation process of compound glabrous greenbrier rhizome granules |
| CN105381140A (en) * | 2015-11-12 | 2016-03-09 | 青岛华仁技术孵化器有限公司 | Medicine for treating qi stagnation and blood stasis type coronary heart disease angina |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1102105A (en) * | 1993-11-03 | 1995-05-03 | 邢春生 | Plaster for curing cough with dyspnea |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1102105A (en) * | 1993-11-03 | 1995-05-03 | 邢春生 | Plaster for curing cough with dyspnea |
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| Title |
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| 韩新民等: "泻肺平喘灵颗粒抗过敏及解痉平喘作用的实验研究", 《河南中医》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104069362A (en) * | 2014-07-02 | 2014-10-01 | 吴新荣 | Preparation process of compound glabrous greenbrier rhizome granules |
| CN105381140A (en) * | 2015-11-12 | 2016-03-09 | 青岛华仁技术孵化器有限公司 | Medicine for treating qi stagnation and blood stasis type coronary heart disease angina |
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Application publication date: 20131218 |