CN101632747B - Preparation technology of children cold relaxation grain - Google Patents
Preparation technology of children cold relaxation grain Download PDFInfo
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- CN101632747B CN101632747B CN2009101845343A CN200910184534A CN101632747B CN 101632747 B CN101632747 B CN 101632747B CN 2009101845343 A CN2009101845343 A CN 2009101845343A CN 200910184534 A CN200910184534 A CN 200910184534A CN 101632747 B CN101632747 B CN 101632747B
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Abstract
The invention discloses a preparation technology of children cold relaxation grains, which comprising the following steps: extracting radix puerariae, herba schizonepetae, platycodon grandiflorum, figwort, liquorice, cicada slough, massa medicata fermentata and burdock in a diacolation way; and then preparing the children cold relaxation grains in a spraying way. The preparation technology has simple and stable production and controllable quality standard; and in addition, the children cold relaxation grains prepared by the technology are effective in treatment.
Description
Technical field
The invention belongs to field of traditional Chinese medicine pharmacy, be specifically related to a kind of preparation technology of Ganmaoshu Keli for children.
Background technology
Infantile fever caused by exogenous pathogens is a modal disease in children's's period, and sickness rate accounts for first of the pediatric disease.Current, the Chinese medicine of treatment flu mainly is divided into two big classes, the first generic antipyretic and antidotal type, and as Folium Isatidis, Radix Isatidis, Fructus Forsythiae etc., this is most, is anemopyretic cold symptom afterwards by its scope of application of prescription content, has more tangible scorchingly hot symptom; The hot warm class of second generic as Rhizoma Et Radix Notopterygii, Radix Saposhnikoviae, Herba Schizonepetae etc., is applicable to that flu is subjected to cold-evil person, and this is a minority.Think that according to Jiang Yuren professor's clinical experience it is not the simple cold hot problem that belongs to that belongs to that children's goes up the actual state of an illness of feeling clinical manifestation, but it is complicated, the early symptom of infantile fever caused by exogenous pathogens particularly, major part has the performance of exogenous cold interior-heat, or have that folder is frightened concurrently, the characteristics of folder food, folder expectorant.
The prescription of Ganmaoshu Keli for children mainly is made up of eight flavor medical materials such as Radix Puerariae, Herba Schizonepetae, Fructus Arctii.Except that Herba Schizonepetae was omited the hot temperature of tool simply, surplus equal nature and flavor were hot flat in the side, had the diffusing heresy of dispelling wind, and the effect of expelling pathogenic factors from muscles for reducing heat cures mainly infantile fever caused by exogenous pathogens, aversion to wind or aversion to cold, hypohidrosis or lossless, headache, pharyngalgia, cough, tongue fur BOHUANG or in vain thin, exterior cold and interior heat diseases such as floating and rapid pulse.
Monarch drug in the Radix Puerariae side of being, dry root for legume pueraria lobata Pueraria lobata (Willd.) Ohwi, starch-containing, multiple flavones ingredient such as daiazi, the sweet unit of Semen sojae atricolor, puerarin etc. and non-flavones ingredient such as allantoin, cupreol, daucosterol etc. have the effect of the cardiovascular of improvement, antitumor action, raise immunity, antialcoholism action, antiinflammatory and separate hotwork etc.
Herba Schizonepetae is the dry aerial parts of labiate Herba Schizonepetae Shizonepeta tenui folia Briq., and it is about 1～2% that herb contains volatile oil, mainly contains D-menthone, racemization menthone and a small amount of d-limonen in the oil; Also contain monoterpene glycosides, flavone compound and phenolic acid composition in addition in the Herba Schizonepetae.This product has effects such as antipyretic-antalgic, antiinflammatory, resisting pathogenic microbes, anticomplementary, relaxing smooth muscle.
Fructus Arctii is the dry mature fruit of feverfew Fructus Arctii Arctium lappa L., mainly contains lignan component, as arctiin, arctigenin, martairesinol etc.; The oils and fats of oil-containing about 26.1% based on linoleic acid, is oleic acid and linolenic acid secondly in addition.Effects such as Fructus Arctii has antitumor, improves the renal metabolism function, antibiotic, antiviral, wherein Arctiin and aglycon thereof are the effective ingredient that Fructus Arctii is separated table function, it may be the main matter basis of Chinese medicine Fructus Arctii resisiting influenza virus effect.
Radix Platycodonis is the dry root of campanulaceae Platycodon grandiflouorum Platycodon grandiflorum (Jacq.) A.DC., main component is oleanolic acid type five rings three obedient saponin, the chemical compound that other still contain types such as flavone, phenolic acid, steroidal, fatty acid has antiinflammatory, eliminates the phlegm, pharmacological action such as antitussive, analgesia, antitumor and immunomodulating, blood fat reducing.
Radix Scrophulariae is the dry root of goatweed Radix Scrophulariae Scrophularia ningpoensis Hemsl., contain the plain glycosides of iridoids, phenylpropyl alcohol, flavonoid, fatty acid and volatilization wet goods composition, have effects such as analgesic, antiinflammatory, antibiotic, blood sugar lowering, antitumor, expansion artery blood vessel.
Radix Glycyrrhizae is the dry root and rhizome of glycyrrhizic legume Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. Glycyrrhiza inflate Bat. or Glycyrrhiza glabra L. Glycyrrhiza glabra L., mainly contain compositions such as triterpenes, flavone, alkaloid and polysaccharide, have effects such as arrhythmia, blood fat reducing, antipyretic-antalgic, antiulcer, antiinflammatory, resisting pathogenic microbes, detoxifcation.
Periostracum Cicadae is the nymph of cicada Cryptotympana atrata Fabr. Cryptotympanapustulata Fabricius exuviae shell when sprouting wings, contain chemical compounds such as several amino acids, trace element and chitin, organic acid, have effects such as tranquilizing soporific, analgesic, antiallergic, immunosuppressant, reduction capillary permeability.
Massa Medicata Fermentata is the herbal leaven that Herba polygoni hydropiperis, storehouse Auricled Hedyotis Herb, Herba Artemisiae Annuae or the like medicine adding flour, Testa Tritici mixing after fermentation form, contain yeast, lactobacillus, amylase, protease, glycoside, vitamin B etc., have external enwergy induce sweat eliminating evil, the breast but the lining spleen invigorating disappears, the effect of regulating QI to expel dampness.
The preparation technology of original Ganmaoshu Keli for children is for selecting crude drug Radix Puerariae 30-50 weight portion for use, Herba Schizonepetae 2040 weight portions, Radix Platycodonis 15-30 weight portion, Radix Scrophulariae 10-20 weight portion, Radix Glycyrrhizae 5-15 weight portion, Periostracum Cicadae 15-30 weight portion, Massa Medicata Fermentata 20-40 weight portion, Fructus Arctii 20-40 weight portion, earlier Herba Schizonepetae is extracted Herba Schizonepetae oil or uses the carbon dioxide supercritical fluid extraction Herba Schizonepetae oil with vapor distillation, with above-mentioned Fructus Arctii, Radix Puerariae, Radix Platycodonis, Radix Scrophulariae becomes coarse powder with Radix Glycyrrhizae powder, use the 50%-80% ethanol percolation, after percolate reclaims ethanol, be concentrated into relative density after being 1.20-1.25 under 80 ℃ the condition, again through cooling, water precipitating; Supernatant filters, and gets filtrate, and is standby; Take by weighing an amount of cyclodextrin, after adding water and making saturated aqueous solution, add Herba Schizonepetae oil, stir, after enclose is finished, leave standstill, cold preservation filters, and after the gained clathrate drying, is ground into fine powder, is the Herba Schizonepetae oil clathrate; Above-mentioned percolation gained filtrate is concentrated into relative density under 80 ℃ condition, is being the clear paste of 1.30-1.35; With spissated clear paste and Herba Schizonepetae oil clathrate mix homogeneously, granulate, just made former Ganmaoshu Keli for children.
But there are many weak points in original Ganmaoshu Keli for children technology: (1) is used steam distillation and is extracted Herba Schizonepetae volatile oil, and the yield parameter of volatile oil is bigger, and the Herba Schizonepetae oil penetrating odor is big, children's's poor compliance; (2) water precipitating method adopts paraffin to be adsorbed in the extracting solution Fructus Arctii is carried out defat, and efficient is low, defat is incomplete; (3) extraction process complexity, production procedure is long, and the rate of extract height is unsuitable for industrialized great production.
Summary of the invention
The objective of the invention is provides a kind of preparation technology of Ganmaoshu Keli for children in order to overcome above-mentioned weak point.
The objective of the invention is to realize by following scheme:
A kind of preparation technology of Ganmaoshu Keli for children, select crude drug Radix Puerariae 30-50 weight portion, Herba Schizonepetae 20-40 weight portion, Radix Platycodonis 15-30 weight portion, Radix Scrophulariae 10-20 weight portion, Radix Glycyrrhizae 5-15 weight portion, Periostracum Cicadae 15-30 weight portion, Massa Medicata Fermentata 20-40 weight portion for use, Fructus Arctii 20-40 weight portion is characterized in that this technology may further comprise the steps:
With above-mentioned medical material Radix Puerariae, Herba Schizonepetae, Radix Platycodonis, Radix Scrophulariae, Radix Glycyrrhizae, Periostracum Cicadae, Massa Medicata Fermentata and Fructus Arctii mix homogeneously, be ground into coarse powder, adding mass percent concentration is the ethanol of 70-90%, percolation speed percolation with per kilogram medical material 4-20mL/min, collect percolation medical material gross weight 3-5 percolate doubly, spray granulation behind the percolate concentrate drying;
Perhaps with above-mentioned medical material Radix Puerariae, Herba Schizonepetae, Radix Platycodonis, Radix Scrophulariae, Radix Glycyrrhizae, Periostracum Cicadae, Massa Medicata Fermentata and Fructus Arctii mix homogeneously, be ground into coarse powder, adding mass percent concentration is the ethanol of 70-90%, percolation speed percolation with per kilogram medical material 4-20mL/min, collect percolation medical material gross weight 3-5 percolate doubly, percolate is carried out ultrafiltration, again ultrafiltrate is condensed into spray granulation behind the extractum; Wherein, the ultrafilter membrane aperture is 50nm, and membrane area is 0.2m
2
Described spray granulation mixes for getting sucrose and dextrin, as the spray granulation carrier, during spray granulation, inlet temperature be 100～120 ℃, temperature of charge be 55～65 ℃, when the speed of peristaltic pump is 18～22rph.
Above-mentioned Ganmaoshu Keli for children is Radix Puerariae 40 weight portions, Herba Schizonepetae 30 weight portions, Radix Platycodonis 25 weight portions, Radix Scrophulariae 15 weight portions, Radix Glycyrrhizae 10 weight portions, Periostracum Cicadae 20 weight portions, Massa Medicata Fermentata 30 weight portions with the weight portion of crude drug preferably, Fructus Arctii 30 weight portions.
The preparation technology of above-mentioned Ganmaoshu Keli for children specifically may further comprise the steps:
With raw medicinal material Radix Puerariae, Herba Schizonepetae, Radix Platycodonis, Radix Scrophulariae, Radix Glycyrrhizae, Periostracum Cicadae, Massa Medicata Fermentata and Fructus Arctii mix homogeneously, be ground into coarse powder, 70% the soak with ethanol 2-10h that adds 1 times of amount of medical material gross weight, then with the percolation speed percolation of per kilogram medical material 6-14mL/min, collect the percolate of 5 times of percolation medical material gross weights, be condensed into extractum; With the mixing fine powders of cane sugar powder and dextrin as the spray granulation carrier, with the extractum spray granulation, drying, promptly; Inlet temperature be 110 ℃, temperature of charge be 55～65 ℃, when the speed of peristaltic pump is 20rph;
Perhaps with Radix Puerariae, Herba Schizonepetae, Radix Platycodonis, Radix Scrophulariae, Radix Glycyrrhizae, Periostracum Cicadae, Massa Medicata Fermentata and Fructus Arctii mix homogeneously, be ground into coarse powder, 70% the soak with ethanol 6-8h that adds 1 times of amount of medical material gross weight, with the percolation speed percolation of per kilogram medical material 6-14mL/min, collect the percolate of 5 times of percolation medical material gross weights then; Get percolate, carry out ultrafiltration under 25 ℃ of conditions, the ultrafilter membrane aperture is 50nm, and membrane area is 0.2m
2, collect the ultrafiltrate of the percolation liquid measure of 1 times of amount of percolation medical material gross weight at ultra-filtration process; Again ultrafiltrate is condensed into the extractum of in the time of 80 ℃, surveying relative density 1.20; Get the sucrose grinding and sieving, with the mixing fine powders of cane sugar powder and dextrin as the spray granulation carrier, with the extractum spray granulation, drying, promptly; Inlet temperature be 110 ℃, temperature of charge be 55～65 ℃, when the speed of peristaltic pump is 20rph.
Monarch drug Radix Puerariae in the side, its main effective ingredient flavonoid is soluble in ethanol, and Radix Puerariae starch content is very high, meets water and heats easy gelatinizing, makes leachate be difficult to filter, so carry with ethanol percolation.Herba Schizonepetae contains volatile oil, and many at present employing steam distillations extract, but because the defective of big production equipment is difficult to reach ideal oil-water separation; Though the employing supercritical CO is arranged
2Abstraction technique extracts Herba Schizonepetae volatile oil, but because Herba Schizonepetae light weight, oil content are low, and large-scale production efficient is low, cost is higher, thereby is not suitable for industrialization and extracts Herba Schizonepetae volatile oil, so Herba Schizonepetae is adopted ethanol extraction.The effective ingredient of all the other medical materials all dissolves in certain density ethanol, therefore according to the principle of obeying monarch drug, directly adopts finite concentration ethanol to carry out percolation to above 8 flavor medical materials and extracts, and method is simple, and effective ingredient can extract fully.
Still there are some problems in traditional impurity removal process such as alcohol extracting-water precipitating etc.: at first effective ingredient may be mingled with and gone out in the precipitation; Secondly impurity-eliminating effect is undesirable, and the solid yield is higher; The 3rd, operation is more and need a large amount of solvents, causes the waste of resource.The hyperfiltration technique that the present invention adopts can be removed the macromole soluble impurity, reduces dose, plurality of active ingredients in the reservation side as often as possible simultaneously, and do not need to expend a large amount of solvents, operation few, with short production cycle, reduce production costs.Spray granulation technology system with extractum mix with adjuvant, multiple working procedures such as granulation, drying are by finishing in the granulation of a totally-enclosed environment under the computer control operation, the present invention adopts the spray granulation technology to granulate, can avoid granule to dry the destruction that causes effective ingredient for a long time, reduce the consumption of adjuvant, the present invention adopts this technology, and the adjustment technology parameter, the even particle size of formation, the profile rounding, the granule of good fluidity.The concrete technological process of production as shown in Figure 1.
Beneficial effect of the present invention: technology of the present invention obtained big or small evenly, particulate while of good fluidity, simplified production procedure greatly, shortened the production cycle, constant product quality is controlled, has improved production efficiency; And technology of the present invention has reduced the rate of extract, has also improved the taste of preparation, has improved the compliance of infant.In sum, the new technology Ganmaoshu Keli for children all is greatly improved than former technology from aspects such as extraction and preparations shaping, quality controls.
Adopt different preparation technologies at different raw materials in this technology, make the effective site of each raw material can access abundant application, and reduced side effect, be embodied in the following aspects:
Experiment material: all purchase in Bozhou City medical material head office pharmaceuticals, all meet regulation under 2005 editions one each medical material item of Chinese Pharmacopoeia through checking every inspection.
Reagent and reagent: puerarin (Nat'l Pharmaceutical ﹠ Biological Products Control Institute, 110752-200511); Dextrin (mountains and rivers, Anhui pharmaceutic adjuvant company, lot number: 081023); Sucrose (the expensive sugared limited company in Guangxi, lot number: 080905); Stevioside (Shandong Sheng Wang, lot number: 080407) methanol is chromatographically pure; All the other are analytical pure.
(1) research of percolation technology
1, single factor of percolation volume is investigated
Get 8 flavor medical material 417g coarse powder such as Radix Puerariae, mixing, pack in the percolation bucket, the soak with ethanol 6h that adds 1 times 70%, then with the percolation speed percolation of 6mL/min, collect the percolate of 3,5,7,9,11 times of recipe quantities respectively, to investigate collected volume to puerarin total amount in the percolate and the heavy influence of dried cream.
Measuring in 3～11 times of recipe quantity percolates puerarin total amount and dried cream heavy, see table 1 for details.
Table 1 percolation volume list factor is investigated the result
Above result shows that after percolate was collected 5 times of recipe quantity volumes, puerarin total amount and dried cream heavily increased slower.
2, Orthogonal Experiment and Design screening technology
Measure 8 flavor medical material 417g coarse powder such as Radix Puerariae by 1/10 prescription, mixing in the percolation bucket of packing into, adds 1 times of Different concentrations of alcohol and soaks 6h, collects percolate by certain percolation speed then, and measures content of puerarin in the percolate.Experimentize according to Orthogonal Experiment and Design,, puerarin total amount heavy with dried cream is evaluation index, investigates the influence of each factor level to the percolation effect, screens best percolation technology.
Orthogonal Experiment and Design: the factor to the percolation influential effect has concentration of alcohol (A), collected volume (B) and percolation speed (C).According to orthogonal table L
9(3
4) contrived experiment carries out the screening of best percolation technology.Factor level sees Table 2.
Table 2 orthogonal test factor level table
Comprehensive grading is carried out intuitive analysis, and the influence size of each factor is A＞B＞C, determines that best percolation technology is A
1B
3C
2, promptly 70% ethanol is collected 5 times of amounts, and percolation speed is 6mL/min.
(2) research of ultrafiltration technology
1, the preparation of sample
Get 8 flavor medical material 417g coarse powder such as Radix Puerariae, mixing in the percolation bucket of packing into, adds 70% soak with ethanol 6h, the percolation speed of pressing 6mL/min then, and the percolate of 5 times of recipe quantity volumes of collection filters with 350 order filter clothes, and is standby.
2, experimental technique: pour percolate into charging basket, open pump inlet valve, membrane module terminal valve, main valve, close blowoff valve, start circulating pump, open membrane module percolation side outlet faucet and collect filtrate.At pressure is that 0.16MPa, feed temperature are under 25 ℃ the condition, makes percolate pass through ceramic membrane, measures solid content slip in the ultrafiltrate, effective ingredient retention rate and the relatively variation of composition in the medicinal liquid before and after the ultrafiltration.
3, the screening of membrane aperture
Get that above-mentioned solution selects 50,100 respectively, the ceramic membrane in 200nm aperture carries out ultrafiltration, collect the 500mL ultrafiltrate, the results are shown in Table 3, the ceramic membrane in 50nm aperture to solid content slip and effective ingredient retention rate than 200,100nm aperture ceramic membrane effective, therefore determine to carry out ultrafiltration with the ceramic membrane in 50nm aperture.
Table 3 membrane aperture The selection result
4, the ultrafiltration volume determines
Get above-mentioned solution and carry out ultrafiltration, and in concentrated solution, add isopyknic solvent, in ultra-filtration process, collect 70% ethanol of 1 times, 1.25 times, 1.5 times volume respectively, collect ultrafiltrate with the ceramic membrane of 50nm.After treating that ultrafiltration finishes, get 500mL ultrafiltrate mensuration active constituent content wherein, calculate retention rate and solid content slip.The results are shown in Table 4,5, after ultrafiltration went out 1 times of percolate volume, effective ingredient retention rate and solid content slip changed not remarkable, therefore in order to reduce cost, determined that the ultrafiltration volume is 1 times of percolate volume.
Table 4 ultrafiltration volume is investigated result ()
Table 5 ultrafiltration volume is investigated result (two)
Get three batches of percolate extracting solution, (aperture is 50nm, and membrane area is 0.2m to carry out ultrafiltration under 25 ℃ of conditions
2), and in concentrated solution, add 1 times of amount solvent, and collect 70% ethanol of 1 times of amount at ultra-filtration process, collect ultrafiltrate.After treating that ultrafiltration finishes, get 500mL ultrafiltrate mensuration active constituent content wherein, calculate retention rate and solid content slip, the result shows that this process stabilizing is feasible.
5, concentration technology
Above-mentioned three batches of ultrafiltrates are placed concentrating under reduced pressure equipment, and thickening temperature is 60 ℃, and vacuum 0.08MPa is concentrated to relative density 1.20 (80 ℃ of surveys).
Heavy * 100% dried cream yield of the rate of extract=extractum weight/medical material=dried cream weight/medical material heavy * 100%
Table 6 concentrates tables of data
(3) research of preparations shaping technology
1, the screening of adjuvant
Because extractum flavor is bitter, need to add suitable adjuvant dilution and flavoring, alternative costs are cheap, be easy to get, the adjuvant of safety, and the consumption of adjuvant is screened.The results are shown in Table 7, when dextrin: during sucrose=1: 4, mouthfeel is better.
Table 7 adjuvant The selection result
2, the screening of spray granulation process conditions
Get that sucrose is pulverized and cross 100 mesh sieves, as the spray granulation carrier, opening device sprays into extractum, makes granule with the mixing fine powders of cane sugar powder and dextrin, drying, promptly.With qualified granule recovery rate and granulation time is evaluation index, screens best granulating process.
Granule yield=actual production/theoretical yield * 100%
(1) the extractum relative density determines
In 55～65 ℃ of temperature of charge, 110 ℃ of inlet temperature, peristaltic pump speed is that the extractum to different relative densities (80 ℃) carries out spray granulation under the 20rph condition, compares with qualified particulate yield, color and luster and granulation time.The results are shown in Table 8, when the extractum relative density was 1.20 (80 ℃), the granulation time was shorter, and the granule color and luster is even.
Table 8 relative density The selection result
(2) spray granulation determination of main technical parameters
The extractum that with relative density is 1.20 (80 ℃) carries out spray granulation according to following different technologies parameter, estimates with granule yield, granulating efficiency.Experimental result sees Table 9, when inlet temperature be 110 ℃, temperature of charge be 55～65 ℃, when the speed of peristaltic pump is 20rph, granulating efficiency is preferable.
The screening of table 9 spray granulation condition
3, the mensuration of angle of repose
Adopt the fixed funnel method with 3 funnels series connection and be fixed in the height place of 2cm on the graph paper of horizontal positioned, the granule that makes poured into along hopper walls respectively go up most in the funnel, till medicated powder cone tip, lower end touches bell mouth, measure the diameter of conical base by graph paper, calculate angle of repose (tg α=h/r).The results are shown in Table 10, show this particulate angle of repose less than 40 °, good fluidity is easy to packing.
The measurement result of table 10 granule angle of repose
In order to verify the feasibility of process optimization result of the test in big production, carry out three batches of pilot scales according to aforementioned optimised process.The average yield rate of the granule of pilot scale is 92%, and grain color is even, rounding, and this process stabilizing, amplification is produced practical.
Ultrafiltration is a kind ofly to carry out the filterable membrane separating method of selectivity by particle diameter.Ultrafilter membrane is the core in the ultrafiltration system, and its aperture between 3～300nm, is selected the ultrafilter membrane in different apertures for use usually, the material of relative molecular weight between hundreds of～hundreds of thousands can be separated, so ultrafilter membrane is the key that influences the ultrafiltration quality
[9], so this experiment to 50,100, the ceramic membrane in 200nm aperture screens.Secondly, the volume of ultrafiltration also is one of factor that influences the ultrafiltration quality.Along with the carrying out of ultrafiltration, remaining liquor strength increases, and causes filtering velocity to slow down, and at this moment the micromolecule effective ingredient adds the transit dose that the solvent dilution residual liquor can improve effective ingredient easily by impurity absorption.On the other hand, the volume of ultrafiltration is excessive also can to extend manufacture cycle, and increases production cost.Therefore, need filter out industrial optimum volume,
Spray-drying pelleting machine is spray drying technology and airpillow-dry technology to be organically combined and the novel pharmaceutical equipment developed, and it merges multiple working procedures such as the mixing of extractum and adjuvant, granulation, drying.The key of spray granulation is to control temperature of charge, when temperature of charge was high, the heat that material stores can be rapidly with the moisture evaporate to dryness of drop, and the adhesion between drop and the granule reduces, therefore the drop that rests on the granule is easy to be worn away in fluid mapper process, is not easy to form bulky grain; And temperature of charge is when low, and the drop that rests on the granule increases the viscosity of particle surface, thereby makes particle bond agglomerating, causes the pot that collapses easily.Temperature of charge is relevant with peristaltic pump speed with an inlet temperature.When an inlet temperature was high, temperature of charge was corresponding higher, easily made granule glue wall, otherwise temperature of charge is low excessively; When peristaltic pump speed was fast, temperature of charge was corresponding lower, the easy adhesion of granule and cause the pot that collapses; Otherwise temperature of charge is too high.The relative density of extractum is also influential to molding particles.When the relative density of extractum was high, the surface tension of drop was bigger, be difficult for sprawling at particle surface, thereby adhesion formed sheet-like particle; Otherwise the particulate speed of growth is slower, and production efficiency is low.
4, brief summary
The present invention screens process conditions, the following technological parameter of optimization: use 70% ethanol, carry out percolation with the percolation speed of per kilogram medical material 14mL/min, collect 5 times of amount percolates, percolate is condensed into extractum; Perhaps percolate is carried out ultrafiltration with the ceramic membrane of aperture 50nm to percolate again, collect the ultrafiltrate of 1 times of percolation liquid measure; Ultrafiltrate is condensed into the extractum that relative density is 1.20 (80 ℃), with dextrin: Icing Sugar=1: 4 is a bed material, inlet temperature is that 110 ℃, temperature of charge are that 55～65 ℃, peristaltic pump speed are to carry out spray granulation under the condition of 20rph, and the gained grain color is even, rounding.Whether the present invention carries out ultrafiltration does not influence the curative effect that obtains product.
Pharmacodynamic experiment of the present invention:
This experiment confirms its main pharmacodynamics effect to Ganmaoshu Keli for children analgesic activity and bacteriostasis pharmacodynamic experiment that prepared of the present invention obtains.
Experiment material:
Medicine and reagent
1, reagent: new technology Ganmaoshu Keli for children of the present invention (preparing by embodiment 1 method), former technology Ganmaoshu Keli for children (081002) are sepia extractum powder, provide by Nanjing Zhongshan Pharmaceutical Co., Ltd.,, face with the preceding even suspension that is mixed with desired concn that grinds with 0.5%CMC-Na.
Ibuprofen: Sino-America Tianjin Shike Pharmaceutical Co., Ltd., lot number: 05040122
2, cleaning level mice, source: Nantong University's Experimental Animal Center, credit number: scxk (Soviet Union) 2003-0002.Feedstuff: pellet is provided by animal reproduction field, Jiangning District Green Dragon mountain, Nanjing.
3, bacterial strain: staphylococcus aureus, escherichia coli, bacillus pyocyaneus, bloodthirsty hemophilus influenza, Klebsiella pneumonia, Diplococcus pneumoniae, clinical isolates strains such as streptococcus separate from clinical different specimens by First People's Hospital, Nanjing Bacteriology Room and identify after provide.
Experimental technique and result:
1, the influence of new technology Ganmaoshu Keli for children group Dichlorodiphenyl Acetate induced mice writhing response
1) experimental technique: get 40 of mices, body weight 18-22g.Be divided into 4 groups at random, 10 every group, male and female half and half.Be model control group, positive controls, new technology Ganmaoshu Keli for children, former technology Ganmaoshu Keli for children group.New technology Ganmaoshu Keli for children, former technology Ganmaoshu Keli for children group dosage are identical.Positive controls gives ibuprofen 30mg/kg.Model control group gives isopyknic 0.5%CMC-Na solution.The administration volume is 0.4ml/20g.Each organizes mice continuous irrigation stomach 5 days, irritate stomach last day after 30min, the equal lumbar injection 0.6% acetic acid 0.2ml/ of each Mus is only.Observe the number of times that writhing response (abdominal part indent, stretch hind leg, buttocks is raised) appears in each Mus in 15 minutes, and calculate inhibition percentage rate (%) of each group, the results are shown in Table 11.
Influence (X ± S) (n=10) of table 11 new technology Ganmaoshu Keli for children group (i.g) Dichlorodiphenyl Acetate induced mice writhing response
Annotate: * P＜0.05, compare with model control group * * P＜0.01
2) experimental result: as seen by table 11, new technology Ganmaoshu Keli for children dosage group can extremely significantly suppress the mouse writhing reaction (P＜0.01) that lumbar injection acetic acid causes, former technology Ganmaoshu Keli for children dosage group can significantly suppress the mouse writhing reaction (P＜0.05) that lumbar injection acetic acid causes.
2, the research of bacteriostasis:
(1) new technology Ganmaoshu Keli for children group is to the antibiotic test of pesticide effectiveness of common clinical bacteria
Experimental technique: the test of new technology Ganmaoshu Keli for children group in-vitro antibacterial, employed culture medium is general MH culture medium (shanghai Medicine chemistry institute product) in the test.Must add 5% defat Sanguis caprae seu ovis (solid agar culture medium) or sheep blood serum (fluid medium) to the higher bacterial strain of nutritional requirement such as Diplococcus pneumoniae, streptococcus etc.
Adopt the double dilution method of agar to measure minimum inhibitory concentration (MIC).
1. the preparation of pastille flat board
Precision quantitatively takes by weighing test specimen, carries out doubling dilution, makes each medicinal liquid become a series of Concentraton gradient, is successively: 100,50,25,12.5,6.25,3.13,1.56,0.78, and 0.39,0.20 (mg/ml).Get each gradient medicinal liquid 2ml then, join respectively in the aseptic plate (plate diameter 9cm), add the MH culture medium 18ml of insulation in 55 ℃ of water-baths that has sterilized and melted again, abundant immediately mixing, stand-by after the condensation.Like this, the ultimate density of the dull and stereotyped Chinese medicine of each pastille is followed successively by: 10,5.0,2.5,1.25,0.625,0.313,0.156,0.078, and 0.039,0.020 (mg/ml).Establish blank simultaneously, only add the agar culture medium of 20ml.
2. preparation of test organisms liquid and dibbling
Activatory each test strain is inoculated into respectively in the 2ml culture fluid in advance, 37 ℃ of overnight incubation, and the corresponding culture fluid of reuse is made suitable dilution, bacterial concentration is about: 10
7-10
8(CFU.ml
-1).(control bacterial concentration method: with the optical density of spectrophotometric determination culture fluid, make suitable dilution then) inoculates each test organisms of instrument dibbling on the MH of each pastille culture medium flat plate with multiple spot then, and blank carries out simultaneously.Every some bacteria containing amount is about: 10
4-10
5(CFU).37 ℃, cultivated 24 hours, observe and write down the MIC value of each bacterium, and calculate MIC
50And MIC
90The results are shown in Table 12.
The external antibacterial tests result (MIC:mg/ml) of table 12 new technology Ganmaoshu Keli for children group to 265 strain clinical bacteria strains
By table 12 as seen, new technology Ganmaoshu Keli for children group external in the test strain except bacillus pyocyaneus, stronger antibacterial activity is all arranged.
(2) new technology Ganmaoshu Keli for children group is to antibacterial tests in the body of mouse infection staphylococcus aureus and Diplococcus pneumoniae
Experimental technique: get 140 of white mice, male and female half and half are divided into 14 groups at random, and 10 every group, 7 groups of each inoculation, 7 groups bacterial strain concentration is respectively: 10
10, 10
9, 10
8, 10
7, 10
6, 10
5, 10
4(CFU/ml), staphylococcus aureus lumbar injection infecting mouse, every mouse inoculation bacterium liquid 0.5ml; The Diplococcus pneumoniae collunarium infects respectively organizes mice, and 30 μ l/ only.Dead mouse situation behind the observation inoculation bacterium in the 48h determines that antibacterial causes the minimum bacteria suspension concentration of white mice all dead (100% death), i.e. minimum lethal dose (100%MLD).Bacterium liquid all dilutes with the culture fluid of 5% gastric Mucin.
The 100%MLD of experimental strain (CFU/ml) measurement result is as follows:
Staphylococcus aureus: 10
9CFU/ml.
Diplococcus pneumoniae: 10
8CFU/ml.
After determining 100%MLD, carry out formal bacterium infecting mouse treatment protectiveness test.Get 140 of mices, male and female half and half are divided into 14 groups at random by body weight, and 10 every group, each organizes the bacteria suspension that mice is given 2 times of definite in prerun minimum lethal doses respectively.In 14 groups of mices, 2 groups of test strain infection model groups (each 1 group of staphylococcus aureus and Diplococcus pneumoniae), 12 groups of new technology Ganmaoshu Keli for children group sample sets (6 groups of infection of staphylococcus aureus groups, 6 groups of Diplococcus pneumoniae infected group).Mice is distinguished each medicinal liquid (0.25ml/10g Mus) of oral administration isometric(al) variable concentrations at once after infection.Between the agent of each medicine gradient than being: 1: 0.7.The infection model matched group gives isometric aseptic injection normal saline solution.The reaction of observation mice, the death toll of mice was observed 7 days continuously after record infection inoculation and the administration, pressed the medicine median effective dose ED of Bliss method calculating to infectious bacteria
50And 95% fiducial limit.The results are shown in Table 13,14.
Table 13 new technology Ganmaoshu Keli for children group is to the endogenous protective result of the test (n=10) of infection of staphylococcus aureus mice
Table 14 new technology Ganmaoshu Keli for children group is to the endogenous protective result of the test of Diplococcus pneumoniae infecting mouse
By table 13,14 as seen, sample new technology Ganmaoshu Keli for children group all has certain treatment protection active to mouse infection staphylococcus aureus and Diplococcus pneumoniae.
Description of drawings
Fig. 1 is a Ganmaoshu Keli for children preparation technology flow chart.
The specific embodiment
The invention will be further elaborated by the following examples.
Embodiment 1
Prescription: Radix Puerariae 400g, Herba Schizonepetae 300g, Radix Platycodonis 250g, Radix Scrophulariae 150g, Radix Glycyrrhizae 100g, Periostracum Cicadae 200g, Massa Medicata Fermentata 300g, Fructus Arctii 300g.
Preparation technology:
With Radix Puerariae, Herba Schizonepetae, Radix Platycodonis, Radix Scrophulariae, Radix Glycyrrhizae, Periostracum Cicadae, Massa Medicata Fermentata and Fructus Arctii mix homogeneously, be ground into coarse powder, the mass percent concentration that adds 1 times of amount of medical material gross weight is behind 70% the soak with ethanol 6h, then with the percolation speed percolation of per kilogram medical material 6mL/min, collect the percolation medical material and weigh 5 times percolate, percolate is dried to extractum; With the mixing fine powders of sucrose and dextrin (by weight dextrin: sucrose=1: 4) mix as the spray granulation carrier, with the extractum spray granulation; Inlet temperature is that 110 ℃, temperature of charge are 55～65 ℃, when the speed of peristaltic pump is 20rph, make Ganmaoshu Keli for children.
Embodiment 2
Prescription: Radix Puerariae 300g, Herba Schizonepetae 400g, Radix Platycodonis 300g, Radix Scrophulariae 100g, Radix Glycyrrhizae 150g, Periostracum Cicadae 300g, Massa Medicata Fermentata 400g, Fructus Arctii 400g.
Preparation technology:
With Radix Puerariae, Herba Schizonepetae, Radix Platycodonis, Radix Scrophulariae, Radix Glycyrrhizae, Periostracum Cicadae, Massa Medicata Fermentata and Fructus Arctii mix homogeneously, be ground into coarse powder, 80% the soak with ethanol 10h that adds 1 times of amount of medical material gross weight, then with the percolation speed percolation of per kilogram medical material 14mL/min, collect the percolate of 3 times of percolation medical material gross weights, percolate is dried to extractum; With the mixing fine powders of cane sugar powder and dextrin (by weight dextrin: sucrose=1: 4) as the spray granulation carrier, with the extractum spray granulation, drying, promptly; Inlet temperature is that 110 ℃, temperature of charge are 55～65 ℃, when the speed of peristaltic pump is 20rph, make Ganmaoshu Keli for children.
Embodiment 3
Prescription: Radix Puerariae 500g, Herba Schizonepetae 200g, Radix Platycodonis 150g, Radix Scrophulariae 200g, 50 parts of g of Radix Glycyrrhizae, Periostracum Cicadae 150g, Massa Medicata Fermentata 200g, Fructus Arctii 200g;
Preparation technology:
With Radix Puerariae, Herba Schizonepetae, Radix Platycodonis, Radix Scrophulariae, Radix Glycyrrhizae, Periostracum Cicadae, Massa Medicata Fermentata and Fructus Arctii mix homogeneously, be ground into coarse powder, add 90% soak with ethanol 8h of 1 times of amount of medical material gross weight,, collect the percolate of 4 times of percolation medical material gross weights then with the percolation speed percolation of per kilogram medical material 8mL/min; Get percolate, carry out ultrafiltration under 25 ℃ of conditions, the ultrafilter membrane aperture is 50nm, and membrane area is 0.2m
2, collect the ultrafiltrate of the percolation liquid measure of 1 times of amount of percolation medical material gross weight at ultra-filtration process; Again ultrafiltrate is condensed into the extractum of in the time of 80 ℃, surveying relative density 1.20; Get the sucrose grinding and sieving, with cane sugar powder and dextrin (by weight dextrin: mixing fine powders sucrose=1: 4) is as the spray granulation carrier, with the extractum spray granulation, drying, promptly; Inlet temperature is that 120 ℃, temperature of charge are 55～65 ℃, when the speed of peristaltic pump is 20rph, make Ganmaoshu Keli for children.
Claims (4)
1. the preparation technology of a Ganmaoshu Keli for children, select crude drug Radix Puerariae 30-50 weight portion, Herba Schizonepetae 20-40 weight portion, Radix Platycodonis 15-30 weight portion, Radix Scrophulariae 10-20 weight portion, Radix Glycyrrhizae 5-15 weight portion, Periostracum Cicadae 15-30 weight portion, Massa Medicata Fermentata 20-40 weight portion for use, Fructus Arctii 20-40 weight portion is characterized in that this technology may further comprise the steps:
With above-mentioned medical material Radix Puerariae, Herba Schizonepetae, Radix Platycodonis, Radix Scrophulariae, Radix Glycyrrhizae, Periostracum Cicadae, Massa Medicata Fermentata and Fructus Arctii mix homogeneously, be ground into coarse powder, adding mass percent concentration is the ethanol of 70-90%, percolation speed percolation with per kilogram medical material 4-20mL/min, collect percolation medical material gross weight 3-5 percolate doubly, spray granulation behind the percolate concentrate drying;
Perhaps with above-mentioned medical material Radix Puerariae, Herba Schizonepetae, Radix Platycodonis, Radix Scrophulariae, Radix Glycyrrhizae, Periostracum Cicadae, Massa Medicata Fermentata and Fructus Arctii mix homogeneously, be ground into coarse powder, adding mass percent concentration is the ethanol of 70-90%, percolation speed percolation with per kilogram medical material 4-20mL/min, collect percolation medical material gross weight 3-5 percolate doubly, percolate is carried out ultrafiltration, again ultrafiltrate is condensed into spray granulation behind the extractum; Wherein, the ultrafilter membrane aperture is 50nm, and membrane area is 0.2m
2
2. the preparation technology of a kind of Ganmaoshu Keli for children according to claim 1, it is characterized in that described spray granulation mixes for getting sucrose and dextrin, as the spray granulation carrier, during spray granulation, inlet temperature is that 100～120 ℃, temperature of charge are that 55～65 ℃, the speed of peristaltic pump are 18～22rph.
3. the preparation technology of a kind of Ganmaoshu Keli for children according to claim 1, it is characterized in that selecting the weight portion of crude drug for use is Radix Puerariae 40 weight portions, Herba Schizonepetae 30 weight portions, Radix Platycodonis 25 weight portions, Radix Scrophulariae 15 weight portions, Radix Glycyrrhizae 10 weight portions, Periostracum Cicadae 20 weight portions, Massa Medicata Fermentata 30 weight portions, Fructus Arctii 30 weight portions.
4. the preparation technology of a kind of Ganmaoshu Keli for children according to claim 1 is characterized in that this technology specifically may further comprise the steps:
With raw medicinal material Radix Puerariae, Herba Schizonepetae, Radix Platycodonis, Radix Scrophulariae, Radix Glycyrrhizae, Periostracum Cicadae, Massa Medicata Fermentata and Fructus Arctii mix homogeneously, be ground into coarse powder, 70% the soak with ethanol 2-10h that adds 1 times of amount of medical material gross weight, then with the percolation speed percolation of per kilogram medical material 6-14mL/min, collect the percolate of 5 times of percolation medical material gross weights, be condensed into extractum; With the mixing fine powders of cane sugar powder and dextrin as the spray granulation carrier, with the extractum spray granulation, drying, promptly; Inlet temperature is that 110 ℃, temperature of charge are that 55～65 ℃, the speed of peristaltic pump are 20rph;
Perhaps with Radix Puerariae, Herba Schizonepetae, Radix Platycodonis, Radix Scrophulariae, Radix Glycyrrhizae, Periostracum Cicadae, Massa Medicata Fermentata and Fructus Arctii mix homogeneously, be ground into coarse powder, 70% the soak with ethanol 6-8h that adds 1 times of amount of medical material gross weight, with the percolation speed percolation of per kilogram medical material 6-14mL/min, collect the percolate of 5 times of percolation medical material gross weights then; Get percolate, carry out ultrafiltration under 25 ℃ of conditions, the ultrafilter membrane aperture is 50nm, and membrane area is 0.2m
2, collect the ultrafiltrate of the percolation liquid measure of 1 times of amount of percolation medical material gross weight at ultra-filtration process; Again ultrafiltrate is condensed into the extractum of in the time of 80 ℃, surveying relative density 1.20; Get the sucrose grinding and sieving, with the mixing fine powders of cane sugar powder and dextrin as the spray granulation carrier, with the extractum spray granulation, drying, promptly; Inlet temperature is that 110 ℃, temperature of charge are that 55～65 ℃, the speed of peristaltic pump are 20rph.
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| CN110917264B (en) * | 2019-12-30 | 2021-08-10 | 南京中山制药有限公司 | Preparation method of oral liquid for treating infantile common cold |
| CN111896672A (en) * | 2020-07-31 | 2020-11-06 | 江苏弘典中药产业研究院有限公司 | Thin-layer identification method of children's Ganmaoshu granules |
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| CN1436569A (en) * | 2003-03-05 | 2003-08-20 | 南京中山制药厂 | Medicine for treating children's cold and its prepn process |
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| CN1436569A (en) * | 2003-03-05 | 2003-08-20 | 南京中山制药厂 | Medicine for treating children's cold and its prepn process |
Non-Patent Citations (2)
| Title |
|---|
| 李燕宁等.中成药治疗小儿急性上呼吸道感染近况.《中国医药指南》.2008,第6卷(第23期),403-404. * |
| 李燕宁等.小儿感冒舒颗粒治疗小儿外感发热(表寒里热证)的双盲观察.《中国中医药信息杂志》.2001,第8卷(第9期),55-56. * |
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Denomination of invention: Preparation of Xiaoer Ganmaoshu Granules Effective date of registration: 20221013 Granted publication date: 20110817 Pledgee: Industrial and Commercial Bank of China Co.,Ltd. Nanjing Zidong Sub branch Pledgor: NANJING ZHONGSHAN PHARMACEUTICAL Co.,Ltd. Registration number: Y2022980018156 |