CN1631429A - Cough stopping formulation and its preparing processes - Google Patents
Cough stopping formulation and its preparing processes Download PDFInfo
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- CN1631429A CN1631429A CN 200410155496 CN200410155496A CN1631429A CN 1631429 A CN1631429 A CN 1631429A CN 200410155496 CN200410155496 CN 200410155496 CN 200410155496 A CN200410155496 A CN 200410155496A CN 1631429 A CN1631429 A CN 1631429A
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Abstract
The invention relates to a cough stopping formulation and its preparing processes, wherein the formulation is prepared from Chinese ephedra, poppy capsule, licorice root, bitter apricot seed, radish seeds, root of platycodon grandiflorum and calcium sulphate. The formulation can be made into the dosage forms including soft extract, oral liquid, syrup or oral tablet.
Description
Technical field: the present invention relates to a kind of cough stopping formulation and preparation method thereof, belong to the field of medicine technology.
Technical background: cough stopping formulation is to develop on the MAXINGSHIGAN TANG basis of China's traditional Chinese medical science famous classic treatise on Febrile Diseases, is total to seven flavor medicine by Herba Ephedrae, Pericarpium Papaveris, Radix Glycyrrhizae, Semen Armeniacae Amarum, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum and forms; Have the lung qi dispersing heat clearing away, cough-relieving, the effect of relievining asthma, to upper respiratory tract infection, tracheitis, pneumonia, diseases such as cough have definite curative effect.The applicant has submitted to name to be called the patent application of " cough stopping formulation and preparation technology thereof " in January, 2004 to Patent Office of the People's Republic of China, and number of patent application is: 2004100217221; The reuse diverse ways was made different dosage forms after this patent application was made microcapsule or micropill earlier with medicine, had improved the bioavailability of medicine.Solved some problems that current techniques exists, but through we discover, still do not reached best therapeutic effect according to the medicine of this method preparation.Because cough, asthma occurs in winter mostly since winter dry weather, patient is except cough, also often with dry throat and mouth, dry cough expectorant is few or do not have symptom such as expectorant, need take and have the medicine of moisturizing the function of promoting the production of body fluid, the therapeutic effect that can play this moment.General solid preparation is not moisturized the effect of promoting the production of body fluid with regard to the characteristics of its dosage form itself, so can not reach optimum therapeuticing effect.And soft extract, oral liquid or syrup, its preparation itself just belongs to moisturizes the product that promote the production of body fluid.If cough-relieving is made soft extract, oral liquid or syrup, take in exsiccant season, add the therapeutical effect of medicine itself, play a multiplier effect surely.Simultaneously soft extract also has the function of tonification, particularly asthma patient because of eipathia asthenia, but takes the soft extract health invigorating also with cough suppressing effect in the winter time, improves the immune disease-resistance ability of body, and recurrence helps warding off disease.The compliance that soft extract, oral liquid and syrup also provide the patient to take this medicine, convenient child, old man, the patient that esophagus is narrower and small, gastrointestinal function is more weak take.For the acute asthma patient, general solid preparation is difficult for taking in addition, and oral cavity disintegration tablet runs into disintegrate rapidly in tens seconds, dispersion after the saliva, and patient does not need water can obey smoothly down.If its cough-relieving is made oral cavity disintegration tablet, directly the through port transmucosal absorbs, and also can avoid the Degradation of first pass effect stomach function regulating, can play the effect that improves bioavailability.
Summary of the invention: the objective of the invention is to: provide to disclose a kind of cough stopping formulation, this preparation comprises soft extract, oral liquid, syrup, oral disintegrating tablet formulation; Another object of the present invention is the preparation method of open these cough stopping formulations of preparation.
The present invention is directed to prior art, the master contains ephedrine according to Herba Ephedrae, alkaloids such as pseudoephedrine, and the Pericarpium Papaveris master contains morphine, codeine, papaverine, narcotoline, alkaloids such as narcotine are so the present invention extracts Herba Ephedrae and Pericarpium Papaveris with semi-biomimetic method.Amygdalate effective ingredient is an amygdaloside, and the amygdaloside hydrolysis can generate hydrocyanic acid, and a spot of hydrocyanic acid can suppress respiratory center, makes respiratory movement be tending towards quiet and reaches function of relieving cough and calming asthma.Soluble in water because of amygdaloside, but easily decomposed by the influence of itself contained emulsin, so Semen Armeniacae Amarum should steam earlier, protect the glycosides purpose to reach enzyme denaturing.Contain multiple saponin in the Radix Platycodonis, sterols, aminoacid, trace element and various saccharides chemical compound are though the effective ingredient of expelling phlegm for arresting cough is mainly platycodin.But contained aminoacid in the Radix Platycodonis, the saccharide trace element, also essential by human body, so use water extraction method.Glycyrrhizic acid has certain therapeutical effect to respiratory tract infection in the Radix Glycyrrhizae, and because of the many forms with salt of glycyrrhizic acid exist, its salt is soluble in water, therefore adopts water extraction method.The chemical constituent CaSO of Gypsum Fibrosum
4It is a kind of indissoluble electrolyte, its ionization process is a dynamic equilibrium, the solubility product that time that decocts and temperature can not influence it, easily stick with paste during decoction in the other drug surface, stop up the cell wall passage, hinder the stripping of other effective ingredient, so the present invention with glycyrrhizic acid content as index, to Radix Glycyrrhizae, Radix Platycodonis, the optimum process condition when Semen Raphani, Gypsum Fibrosum decoct is jointly selected.
The present invention constitutes like this: calculate according to composition by weight: it mainly is prepared from by Herba Ephedrae 120-480, Pericarpium Papaveris 120-480, Radix Glycyrrhizae 120-480, Semen Armeniacae Amarum 120-480, Semen Raphani 37.5-150, Radix Platycodonis 37.5-150, Gypsum Fibrosum 37.5-150.Specifically: it is prepared from by Herba Ephedrae 240, Pericarpium Papaveris 240, Radix Glycyrrhizae 240, Semen Armeniacae Amarum 240, Semen Raphani 75, Radix Platycodonis 75, Gypsum Fibrosum 75.The preparation technology of preparation of the present invention is: Herba Ephedrae, Pericarpium Papaveris is pulverized the back and is extracted with semi-biomimetic method, Semen Armeniacae Amarum steams earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum are soaked, then Semen Armeniacae Amarum together the water decocting method extract, behind the extracting liquid filtering with Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes extractum, adds different adjuvants again, can make different formulation products with diverse ways.Concrete preparation technology is: Herba Ephedrae, Pericarpium Papaveris are pulverized, and add the hydrochloric acid solution that 3-30 doubly measures PH1-5, soak after 0.5-5 hour to decoct 1-10 time, the hydrochloric acid solution of the PH1-5 that each 3-30 of adding doubly measures decocted 0.5-10 hour, filter, merging filtrate, medicinal liquid transfer PH to 6.0-8.0 standby.Semen Armeniacae Amarum steamed 5-500 minute earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 3-30 times of water gaging and soaked 0.5-5 hour, decoct 1-10 time with Semen Armeniacae Amarum then, the decocting that each adding 3-30 doubly measures boiled 0.5-10 hour, filtered filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes extractum, adds different adjuvants again, can make different products with diverse ways.
Technology when the present invention makes soft extract is: Herba Ephedrae, Pericarpium Papaveris are pulverized, adding 3-30 doubly measures the hydrochloric acid solution of PH1-5, soak after 0.5-5 hour and decoct 1-10 time, the hydrochloric acid solution of the PH1-5 that each 3-30 of adding doubly measures decocted 0.5-10 hour, filter, merging filtrate, medicinal liquid transfer PH to 6.0-8.0 standby.Semen Armeniacae Amarum steamed 5-500 minute earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 3-30 times of water gaging and soaked 0.5-5 hour, decoct 1-10 time with Semen Armeniacae Amarum then, the decocting that each adding 3-30 doubly measures boiled 0.5-10 hour, filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes thick paste, takes by weighing the sucrose that thick paste 0.1-10 doubly measures, and adds the water of sucrose amount more than 40% and is made into sucrose liquid and boils and dissolve, filter, the tartaric acid that adds 0.01-10%, insulation made it to become Nulomoline more than 1 hour.Again above-mentioned gained thick paste is added in the Nulomoline, stir, boil, relative density 1.25～1.65 during cryoconcentration to 60 ℃ o'clock, add 0.05%-0.8% sodium benzoate mixing, cold slightly, drag for floating foam, in time place canned bucket then, sealing is cooled to 70～80 ℃, promptly gets the cough-relieving soft extract.
When making soft extract, the present invention finds that medicine crystallization should occur after placing a period of time, cries sand return again.It is done further research back finds the following aspects controlled and can effectively prevent crystallization: 1, adding tartaric acid in this preparation is because sucrose under the catalysis of acid, can increase the conversion ratio that sucrose hydrolysis is a monosaccharide.2, the 0.1-10 that the sucrose amount should be the thick paste amount in this preparation doubly, if sucrose is excessive, then saturation is excessive, the formation speed of nucleus and crystalline coarsening rate are also accelerated, and easily form crystallization.3, in this preparation, if the water consumption of stirring off is lower than 40% of sucrose amount, the sugar refinery deficiency of time can occur, the sucrose inversion rate does not reach standard, can contain sucrose crystal.4, the sucrose after-filtration that is dissolved in water is in order to have prevented undissolved sucrose crystal.
Owing to contain a large amount of sugar part in the soft extract of the present invention, in storage process, grow microorganism easily, go mouldy, thereby influence the quality of medicine.So can add an amount of antiseptic in the soft extract of the present invention, if but the antiseptic improper use also can influence the quality of medicament.Below be to the choice of preservatives experimental result:
| Project | Cosmetic variation | Mouthfeel | ||||
| 30 days | 60 days | 90 days | 120 days | 180 days | ||
| 0.1% benzoic acid | Numb feeling in the tongue slightly | |||||
| 0.2% benzoic acid | Numb feeling in the tongue slightly | |||||
| 0.1% sodium benzoate | No change | |||||
| 0.2% sodium benzoate | No change | |||||
| 0.03% nipalgin | + | ++ | ++ | ++ | Abnormal flavour is arranged | |
| 0.06% nipalgin | Abnormal flavour is arranged | |||||
| 0.05% potassium sorbate | 0 | 0 | 0 | Become sour | ||
| 0.1% potassium sorbate | 0 | 0 | Become sour | |||
Annotate: the remorse common vetch of Lightening-properties whetstone Xi? expression has a small amount of mycete; ++ expression has mycete; 0 expression fermentation is become sour.
According to experimental result in the table relatively, we select sodium benzoate as antiseptic.
Since sodium benzoate during as antiseptic consumption big more, drug quality is not had obvious variation, but can cause damage human body, the consumption of sodium benzoate is advisable to be no more than 0.8% in this preparation, the selection experimental result of its minimum use amount is:
| Project | Cosmetic variation | Mouthfeel | ||||
| 30 days | 60 days | 90 days | 120 days | 180 days | ||
| 0.01% sodium benzoate | + | ++ | +++ | Abnormal flavour is arranged | ||
| 0.03% sodium benzoate | + | + | Abnormal flavour is arranged | |||
| 0.05% sodium benzoate | No change | |||||
| 0.07% sodium benzoate | No change | |||||
| 0.09% sodium benzoate | No change | |||||
| 0.1% sodium benzoate | No change |
According to experimental result in the table, effective use amount of sodium benzoate is 0.05%-0.8% in this preparation.
Technology when the present invention makes oral liquid is: Herba Ephedrae, Pericarpium Papaveris are pulverized, adding 3-30 doubly measures the hydrochloric acid solution of PH1-5, soak after 0.5-5 hour and decoct 1-10 time, the hydrochloric acid solution of the PH1-5 that each 3-30 of adding doubly measures decocted 0.5-10 hour, filter, merging filtrate, medicinal liquid transfer PH to 6.0-8.0 standby.Semen Armeniacae Amarum steamed 5-500 minute earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 3-30 times of water gaging and soaked 0.5-5 hour, decoct 1-10 time with Semen Armeniacae Amarum then, the decocting that each adding 3-30 doubly measures boiled 0.5-10 hour, filtered filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes thick paste, put cold after, add ethanol and be 40-90% to containing the alcohol amount.Left standstill 5-50 hour, and filtered, filtrate recycling ethanol continues to be condensed into thick paste, and it is an amount of to add water, cold preservation 10-300 hour, filters.Other gets and makes dissolving in the water that an amount of sucrose goes into to boil evenly, filters, and makes simple syrup.With making final sugar content 5-60% in an amount of simple syrup adding said medicine filtrate, add the 0.06%-0.8% sodium benzoate, boil dissolving, add water to full dose, transfer PH to 4-7 with sodium hydroxide, stir evenly, filter, embedding, promptly.
When the present invention makes oral liquid, compare with preparation process, increased the process of precipitate with ethanol, because effective ingredient in the prescription such as ephedrine, codeine phosphate, saponin etc. have certain dissolubility in ethanol, and the almost insoluble and ethanol of impurity such as starch, protein, tannin, resin, so can play the effect of " removing crudely and store essence " with the method for precipitate with ethanol, maximum reservation effective ingredient.After alcohol deposit fluid reclaims ethanol in addition, directly add entry and adjuvant dosing, gained solution muddiness has more precipitation after the placement, in order to improve the solution clarity, can keep effective ingredient as far as possible, and we adopt cold preservation water precipitating method.
Owing to contain a large amount of sugar part in the oral liquid of the present invention, in storage process, grow microorganism easily, go mouldy, thereby influence the quality of medicine.So can add an amount of antiseptic in the oral liquid of the present invention, if but the antiseptic improper use also can influence the quality of medicament.Below be to the choice of preservatives experimental result:
After adding potassium sorbate, sodium benzoate as can be seen from the table, bigger variation does not take place in the character of preparation and main component content thereof, and we further select only a kind of by the mensuration to these two kinds of antiseptic effects.In sample, add 0.2% potassium sorbate, 0.2% sodium benzoate, 0.3% sodium benzoate respectively and be made into 3 test samples of different preservatives, place certain hour.
Assay method and the results are shown in following table:
Measure the bacteriostasis of antiseptic.
| The bacterium name | 0h is to each time clump count reduction multiple | ||||||||
| Benzoic acid (* 10 3) | Potassium sorbate (* 10 3) | Sodium benzoate (* 10 3) | |||||||
| 48h | 7d | 28d | 48h | 7d | 28d | 48h | 7d | 28d | |
| Escherichia coli | 866 | 208 | 200 | 917 | 183 | 177 | 714 | 227 | 200 |
| Staphylococcus aureus | 518 | 400 | 314 | 455 | 253 | 228 | 580 | 435 | 395 |
| Bacillus subtilis | 750 | 286 | 181 | 1160 | 305 | 200 | 1180 | 295 | 281 |
| Mycete | 33 | 0.08 | 0.667 | 38 | 0.067 | 0.4 | 42 | 0.167 | 0.714 |
| Yeast | 340 | 0.638 | 1.02 | 300 | 0.491 | 0.675 | 371 | 0.743 | 0.867 |
From table the result as can be seen each antiseptic for antibacterial stronger killing and the effect of growth always arranged all, weak slightly for mycete and saccharomycetic effect, but still have the effect of killing and suppressing to grow, comparatively speaking, the need testing solution that adds 0.3% sodium benzoate, through the long period placement, it sterilizes, bacteriostasis is more stable for the need testing solution that adds other antiseptic.
Since sodium benzoate during as antiseptic consumption big more, drug quality is not had obvious variation, but can cause damage human body, the consumption of sodium benzoate is advisable to be no more than 0.8% in this preparation, the selection experimental result of its minimum use amount is:
| Project | Cosmetic variation | Mouthfeel | ||||
| 30 days | 60 days | 90 days | 120 days | 180 days | ||
| 0.01% sodium benzoate | + | + | ++ | +++ | Abnormal flavour is arranged | |
| 0.03% sodium benzoate | + | ++ | Abnormal flavour is arranged | |||
| 0.05% sodium benzoate | + | Abnormal flavour is arranged | ||||
| 0.06% sodium benzoate | No change | |||||
| 0.08% sodium benzoate | No change | |||||
| 0.1% sodium benzoate | No change | |||||
According to experimental result in the table, effective use amount of sodium benzoate is 0.06%-0.8% in this preparation.
Technology when the present invention makes syrup is: Herba Ephedrae, Pericarpium Papaveris are pulverized, adding 3-30 doubly measures the hydrochloric acid solution of PH1-5, soak after 0.5-5 hour and decoct 1-10 time, the hydrochloric acid solution of the PH1-5 that each 3-30 of adding doubly measures decocted 0.5-10 hour, filter, merging filtrate, medicinal liquid transfer PH to 6.0-8.0 standby.Semen Armeniacae Amarum steamed 5-500 minute earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 3-30 times of water gaging and soaked 0.5-5 hour, decoct 1-10 time with Semen Armeniacae Amarum then, the decocting that each adding 3-30 doubly measures boiled 0.5-10 hour, filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, and concentrating under reduced pressure becomes thick paste.Other gets an amount of sucrose and adds and make dissolving in the water that boils evenly, filters, and makes simple syrup.With making final sugar content 20-70% in an amount of simple syrup adding said medicine filtrate, add the 0.06%-0.8% sodium benzoate simultaneously.Heating in water bath keeps this temperature to about 35-70 ℃, stirs the 1% chitin hydrochloric acid solution that adds the 0.5-10% volume down, continues to stir 10-60min, filters.Get supernatant and add water to full dose, fill, promptly.
After the present invention was prepared into syrup, some flocky precipitates appearred in this product regular meeting, analyze its reason, may be relevant with the reaction between glycyrrhizic acid and the ephedrine.In addition, contain complicated ingredients such as protein, starch, polysaccharide in the Chinese traditional medicine water extract, these polymer substances are colloid and disperse, and high temperature can destroy colloid during sterilization, and accelerates the oxidation reaction of some composition.Low temperature can reduce colloid power stability, makes it aggregate and precipitate.Make the medicine clarity not high, thereby influence the quality of medicine.The present invention selects, and compares with former technology chitin clarification, alcohol clarification experiment.
One, sample preparation
According to optimal formulation technology, the plain shell of small-mouthed jar is ground into coarse granule, and the Herba Ephedrae cutting adds 10 times of hydrochloric acid solutions of measuring PH3, decocts twice, each 1.5 hours.Filter, merging filtrate, medicinal liquid transfer PH to 7.0 standby.Semen Armeniacae Amarum steamed 30 minutes earlier, Radix Glycyrrhizae, Radix Platycodonis section and Semen Raphani, and Gypsum Fibrosum adds 8 times of water gagings together and soaked 1 hour, adds the water of 10 times of amounts then again with Semen Armeniacae Amarum, decocts twice, each 2 hours.Filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, and suitably concentrates stand for standby use.
The I group: the blank sample, get above-mentioned decoction liquor 100g, join in the sucrose liquid that contains 100g sucrose, add sodium benzoate 0.9g, boil dissolving, add an amount of distilled water to 300ml, filter, promptly.
The II group: clarify sample naturally, get above-mentioned decoction liquor 100g, place centrifuge centrifugal, get supernatant liquid filtering, filtrate joining contains in the sucrose liquid of 100g sucrose, adds sodium benzoate 0.9g, boils dissolving, adds an amount of distilled water to 300ml, filters, promptly.
III group: chitin clarification sample, A: get above-mentioned decoction liquor 100g, join in the sucrose liquid that contains 100g sucrose, add sodium benzoate 0.9g simultaneously, about heating in water bath to 45 ℃, keep this temperature, stir adding 1% chitin hydrochloric acid solution 9ml down, continue to be stirred to a large amount of precipitations of generation.Place centrifuge centrifugal again, get supernatant liquid filtering, add an amount of distilled water to 300ml, promptly.
IV group: alcohol clarification sample, get above-mentioned decoction liquor 100g, add isopyknic 95% ethanol, airtight leaving standstill more than the 12h, put in the centrifuge centrifugal, get supernatant and reclaim ethanol, join again in the sucrose liquid that contains 100g sucrose, add sodium benzoate 0.9g to the greatest extent, boil dissolving, add an amount of distilled water to 300ml, filter, promptly.
Two, clarifying effect is investigated
1, appearance character:
| Group number | The different time clarifying effect | ||||
| 1 day | 2 days | 3 days | 5 days | Color and luster | |
| I | There is floccule to suspend | Floccule is more, is pitchy | The pitchy floccule increases | The pitchy floccule is more | Brown deeply |
| II | Clear | There is floccule on the upper strata | Floccule increases, but lacks than the I group | Floccule is dark brown | Brown |
| IIIA | Clear | Clear | The brown ring appears in the upper strata, the disappearance of rolling | There is a small amount of floccule on the upper strata | Pale brown |
| IIIB | Clear | Clear | There is the disappearance of brown ring rolling on the upper strata | There is a small amount of floccule on the upper strata | Pale brown |
| IV | Clear | There are a small amount of floccule and the sticking wall of granule in the upper strata | Floccule increases | Floccule is less than the II group and organizes more than III | Brown |
2, total solids is measured: smartly claim a certain amount of syrup to put in the culture dish, put into baking oven to parching taking-up, put coldly in exsiccator, weigh rapidly, calculate total solids, the results are shown in following table.
| Group | I | II | III | III | IV |
| Total solids (%) | 49.1 | 48.8 | 48.6 | 48.4 | 48.0 |
From total solids, do not have too big difference between each group, illustrate that chitin adsorption clarification technology does not influence the active substance total amount.This shows that the chitin clarifying effect obviously is better than other each groups, now the consumption of chitin is selected.
| Project | Total solids (%) | Clarity after 3 days |
| 1% chitin hydrochloric acid solution of 0.5% volume | 47.39 | There is a small amount of floccule on the upper strata |
| 1% chitin hydrochloric acid solution of 1% volume | 46.52 | Brown appears in the upper strata |
| 1% chitin hydrochloric acid solution of 2% volume | 46.31 | Brown appears in the upper strata |
| 1% chitin hydrochloric acid solution of 3% volume | 46.18 | Clear |
| 1% chitin hydrochloric acid solution of 5% volume | 44.79 | Clear |
| 1% chitin hydrochloric acid solution of 10% volume | 43.25 | Clear |
By above experimental result as can be known, optimum amount is 1% a chitin hydrochloric acid solution of 3% volume, can guarantee the clarity of medicinal liquid, does not also influence the content of total solid material.
Technology when the present invention makes oral cavity disintegration tablet is: Herba Ephedrae, Pericarpium Papaveris are pulverized, adding 3-30 doubly measures the hydrochloric acid solution of PH1-5, soak after 0.5-5 hour and decoct 1-10 time, the hydrochloric acid solution of the PH1-5 that each 3-30 of adding doubly measures decocted 0.5-10 hour, filter, merging filtrate, medicinal liquid transfer PH to 6.0-8.0 standby.Semen Armeniacae Amarum steamed 5-500 minute earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 3-30 times of water gaging and soaked 0.5-5 hour, decoct 1-10 time with Semen Armeniacae Amarum then, the decocting that each adding 3-30 doubly measures boiled 0.5-10 hour, filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes extractum, drying is ground into the above powder of 60 orders, with low-substituted hydroxypropyl cellulose, 10-50% microcrystalline Cellulose, 2-20% sucrose, the 2-10% Mentholum mix homogeneously of 1-10%, tabletting promptly gets the cough-relieving oral cavity disintegration tablet.
When the present invention makes oral cavity disintegration tablet, how to select proper supplementary material for use, make the compressibility of cough-relieving oral cavity disintegration tablet and outward appearance energy up to specification, particularly can increase the hardness of tablet, and don't influence the maximum difficult point that its disintegrative is this preparation.Below be selection experimental result to adjuvant:
| Collapse the agent agent | Filler | Correctives | The result |
| 7% cross-linked carboxymethyl cellulose sodium | 50% erythrol | Sweet and tasty, the no sand type of cool taste; Compressibility is good; Hardness is good; The 11min disintegrate; | |
| 7% cross-linked carboxymethyl cellulose sodium | 30% microcrystalline Cellulose | 15% sucrose, 3% Mentholum | Little sweet, the Herba Menthae fragrance of mouthfeel; Compressibility is good; The 12min disintegrate; |
| 7% crospolyvinylpyrrolidone | 50% erythrol | Sweet and tasty, the no sand type of cool taste; Compressibility is good; The 15min disintegrate | |
| 7% crospolyvinylpyrrolidone | 30% microcrystalline Cellulose | 15% sucrose, 3% Mentholum | Little sweet, the Herba Menthae fragrance of mouthfeel; Compressibility is good; The 16min disintegrate |
| 7% crosslinked carboxymethylstach sodium | 50% erythrol | Sweet and tasty, the no sand type compressibility of cool taste is better; The 13min disintegrate | |
| 7% crosslinked carboxymethylstach sodium | 30% microcrystalline Cellulose | 15% sucrose, 3% Mentholum | Little sweet, the Herba Menthae fragrance of mouthfeel, compressibility is better; The 13min disintegrate |
| 4% low-substituted hydroxypropyl cellulose | 30% microcrystalline Cellulose | 15% sucrose, 3% Mentholum | Little sweet, the Herba Menthae fragrance of mouthfeel; Compressibility is better; Hardness is good; Outward appearance is bright and clean; The 14min disintegrate |
According to above experimental result, above disintegrating agent, filler and correctives, all can reach the prescription of oral cavity disintegration tablet, after taking all factors into consideration, select for use low-substituted hydroxypropyl cellulose to make disintegrating agent, microcrystalline Cellulose is made filler and sucrose and Mentholum and is made correctives, existing the supplementary product consumption of selecting for use is selected:
1, sees the following form with the factor level table
| Flat | Factor | |||
| A | B | C | D | |
| Low-substituted hydroxypropyl cellulose | Microcrystalline Cellulose | Sucrose | Mentholum | |
| 1 | 1％ | 10％ | 2％ | 2％ |
| 2 | 4％ | 30％ | 10％ | 5％ |
| 3 | 10％ | 50％ | 20％ | 10％ |
2, orthogonal experiment design table and result
| The experiment number | A | B | C | D | The result | Scoring |
| 1 | 1 | 1 | 1 | 1 | Little sweet lighter; Outward appearance is bright and clean; The 19min disintegrate | 66.15 |
| 2 | 1 | 2 | 2 | 2 | Little sweet, Herba Menthae fragrance; Hardness is good; The 17min disintegrate | 71.36 |
| 3 | 1 | 3 | 3 | 3 | Mint flavored is dense; The 19min disintegrate | 69.14 |
| 4 | 2 | 1 | 2 | 3 | Mint flavored is dense; The 14min disintegrate | 76.28 |
| 5 | 2 | 2 | 3 | 1 | Little sweet, Herba Menthae fragrance; Compressibility is better; Hardness is good; Outward appearance is bright and clean; The 13min disintegrate | 88.34 |
| 6 | 2 | 3 | 1 | 2 | Little sweet lighter; Hardness is better; The 18min disintegrate | 65.14 |
| 7 | 3 | 1 | 3 | 2 | Mint flavored is dense; Outward appearance is bright and clean; The 15min disintegrate | 73.36 |
| 8 | 3 | 2 | 1 | 3 | Little sweet lighter; Hardness is good; The 14min disintegrate | 72.98 |
| 9 | 3 | 3 | 2 | 1 | Little sweet, Herba Menthae fragrance; Compressibility is better; The 18min disintegrate | 68.93 |
According to above experimental result, optimum amount is A as can be seen
2B
2C
3D
1, promptly low-substituted hydroxypropyl cellulose is 4%, microcrystalline Cellulose is 30%, sucrose is 20%, Mentholum is 2%.
Study on extraction of the present invention:
One, Pericarpium Papaveris, Herba Ephedrae Study on extraction
1, the factor level table sees the following form:
| Level | Factor | ||||
| A | B | C | D | ||
| Number of times | Decocting time | PH | Add solvent amount (doubly) | The pulverizing medicinal materials degree | |
| 1 | 2 | 1.5、1.5 | 1 | 3 | The Pericarpium Papaveris coarse granule, the Herba Ephedrae cutting |
| 2 | 1 | 10 | 3 | 10 | Fine powder |
| 3 | 10 | 2、1、1、0.5、0.5、0.5 、0.5、0.5、0.5、0.5 | 7 | 30 | Do not pulverize |
2, orthogonal experiment design table and the results are shown in following table:
| Row number the experiment number | A | B | C | D | Yield of extract (%) | Codeine phosphate content (mg/g) | Ephedrine hydrochloride content (mg/g) | Scoring |
| 1 | 1 | 1 | 1 | 1 | 19.518 | 0.9321 | 4.6122 | 68.1 |
| 2 | 1 | 2 | 2 | 2 | 23.900 | 0.8907 | 7.0391 | 83.7 |
| 3 | 1 | 3 | 3 | 3 | 18.806 | 0.8000 | 4.9818 | 65.7 |
| 4 | 2 | 1 | 2 | 3 | 18.711 | 0.9829 | 3.9833 | 65.5 |
| 5 | 2 | 2 | 3 | 1 | 28.590 | 0.7475 | 4.7611 | 69.7 |
| 6 | 2 | 3 | 1 | 2 | 12.391 | 0.7025 | 2.3318 | 43.2 |
| 7 | 3 | 1 | 3 | 2 | 19.550 | 1.3204 | 2.5735 | 68.3 |
| 8 | 3 | 2 | 1 | 3 | 16.533 | 1.0100 | 2.7694 | 57.9 |
| 9 | 3 | 3 | 2 | 1 | 17.160 | 1.1342 | 2.4349 | 60.2 |
Above result optimised process as can be seen is A
1B
2C
2D
2, promptly the plain shell of small-mouthed jar, Herba Ephedrae are ground into fine powder, add the hydrochloric acid solution of 10 times of amount PH3, decoct twice, each 1.5 hours.But the plain shell of small-mouthed jar, Herba Ephedrae are ground into fine powder and filter difficulty in big production, and the influence of D factor is not remarkable, adopts time good technology B
2C
2A
1D
1, promptly the plain shell of small-mouthed jar is ground into coarse granule, and the Herba Ephedrae cutting adds 10 times of hydrochloric acid solutions of measuring PH3, decocts twice, each 1.5 hours.
Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum decocting process are investigated
1, with glycyrrhizic acid content, yield of extract as index.The factor level table sees the following form
| Flat | Factor | |||
| A | B | C | D | |
| Amount of water | Decocting time | Decoct number of times | The pulverizing medicinal materials degree | |
| 1 | 3 | 0.5 | 10 | Radix Glycyrrhizae, Radix Platycodonis section |
| 2 | 10 | 2 | 1 | Coarse granule |
| 3 | 30 | 10 | 2 | Fine powder |
2, orthogonal experiment design table and result
| Row number the experiment number | A | B | C | D | Yield of extract (%) | Glycyrrhizic acid content (mg/g) | Scoring |
| 1 | 1 | 1 | 1 | 1 | 14.9100 | 15.33 | 43.78 |
| 2 | 1 | 2 | 2 | 2 | 27.6305 | 20.96 | 71.86 |
| 3 | 1 | 3 | 3 | 3 | 28.3421 | 17.81 | 69.12 |
| 4 | 2 | 1 | 2 | 3 | 34.0150 | 17.64 | 78.31 |
| 5 | 2 | 2 | 3 | 1 | 42.2413 | 20.27 | 95.21 |
| 6 | 2 | 3 | 1 | 2 | 32.1008 | 18.05 | 75.65 |
| 7 | 3 | 1 | 3 | 2 | 12.9467 | 24.12 | 51.45 |
| 8 | 3 | 2 | 1 | 3 | 20.0090 | 14.70 | 51.44 |
| 9 | 3 | 3 | 2 | 1 | 26.2516 | 19.59 | 67.87 |
Above The results of analysis of variance optimised process as can be seen is A
2B
2C
3D
1Be section of Radix Glycyrrhizae, Radix Platycodonis and Semen Raphani, Gypsum Fibrosum adds 8 times of water gagings together and soaked 1 hour, and Semen Armeniacae Amarum steamed after 30 minutes, adds the water of 10 times of amounts again with above-mentioned soaked medical material, decocts twice, each 2 hours.
In more than forming, every part of representative be weight portion. weight is calculated with crude drug, if be unit with the gram, more than form and can be made into 1000 doses of pharmaceutical preparatioies, described 1000 doses of fingers, the final drug preparation of making, as make oral liquid 1000ml, soft extract 1000ml, syrup 1000ml.
Pharmacodynamic test of active extract
The cough-relieving of cough-relieving soft extract, reduce phlegm, relieving asthma and immunization research:
One, material:
1, medicine: KEKE JIAONANG: according to the method preparation of " cough stopping formulation and preparation technology thereof ".
Cough-relieving soft extract: according to method preparation of the present invention.
2, animal: Cavia porcellus, NIH mice, SD rat provide by Guiyang Medical College.
Two, experimental technique and result
1, cough-relieving experiment: get 36 of NIH mices, male and female half and half are divided into 3 groups at random, are respectively matched group, KEKE JIAONANG group, cough-relieving soft extract group group.Each administration group is gastric infusion 20ml/kg according to dosage, and matched group gives the equal-volume distilled water, every day 1 time, 3d continuously.1h after the last administration puts into sprayer unit with mice and begins to accept spraying, the cough latent period of record mice, and calculate the cough-relieving rate:
Cough-relieving rate %=(administration group cough response time/matched group cough response time) * 100%
The result compares with the KEKE JIAONANG group, and significantly long, the also obviously rising of cough-relieving rate incubation period of cough-relieving soft extract group mouse cough is 186.5%.Compare P＜0.05 with matched group.The result sees following table for details.
| Group | Dosage g crude drug/kg | Cough latent period s | Cough-relieving rate % |
| Matched group | - | 18.73±4.26 | - |
| The KEKE JIAONANG group | 5.4 | 31.92±15.48 | 175.8 |
| Cough-relieving soft extract group | 5.4 | 34.92±12.94 | 186.5 |
2, the experiment of reducing phlegm: capillary glass-tube method, get 30 of SD rats, male and female half and half are divided into 3 groups at random, are respectively matched group, KEKE JIAONANG group, cough-relieving soft extract group.Water 12h is can't help in fasting before each group experiment, urethane 1g/kg intraperitoneal injection of anesthesia, it is fixing to face upward the position, cut off neck middle part skin, isolate trachea, hit exactly between two cartilages at thyroid cartilage lower edge and prick an aperture with sharp-pointed injection needle, insert one of internal diameter 0.8cm capillary glass tube then, make capillary tube just contact the trachea lower surface,, draw sputum length as the effect of reducing phlegm of estimating medicine with capillary tube so as to drawing the sputum at trachea rear portion.After the normal secretory volume of 1h, each administration group is gastric infusion 10ml/kg according to dosage before the record administration, and matched group gives the equal-volume distilled water, and record administration 1h respectively organizes the sputum secretory volume of rat.The results are shown in following table.
| Group | Dosage g/ crude drug/kg | The normal secretory volume cm of sputum | Secretory volume cm behind the sputum medicine |
| Matched group | - | 2.08±0.22 | 2.16±0.15 |
| The KEKE JIAONANG group | 5.4 | 2.13±0.20 | 2.64±0.202) |
| Cough-relieving soft extract group | 5.4 | 2.18±0.16 | 3.31±0.192) |
The result compares with the KEKE JIAONANG group, and the sputum secretory volume of cough-relieving soft extract group rat significantly increases, and compares P＜0.01 with matched group.
3, the experiment of relievining asthma: spraying causes the method for breathing heavily, and gets 30 of Cavia porcelluss, and male and female half and half are divided into 3 groups at random, are respectively matched group, KEKE JIAONANG group, cough-relieving soft extract group.Each administration group is according to dosage irritated flavor administration 10ml/kg, and matched group gives the equal-volume distilled water, every day 1 time, 3d continuously.1h after the last administration by only Cavia porcellus being placed in the device case, starts the WH-96 ultrasound atomizer, sprays into the 1mg/ml histamine phosphate, pick up counting simultaneously, record from spraying begin to time that Cavia porcellus twitches as asthma incubation period, and calculate the asthma suppression ratio.The result compares with matched group, CHUANBEI PIPA GAO is low, in two dosage group Cavia porcellus asthma obviously prolong P＜0.05 and P＜0.01 incubation period.The results are shown in following table.
| Group | Dosage g crude drug/kg | Asthma min incubation period | Asthma suppression ratio % |
| Matched group | - | 2.15±0.47 | - |
| The KEKE JIAONANG group | 5.4 | 2.50±0.65 | 116.3 |
| Cough-relieving soft extract group | 5.4 | 2.69±0.78 | 125.1 |
4, immunization experiment is got 36 of NIH mices, and male and female half and half are divided into 3 groups at random, are respectively matched group, KEKE JIAONANG group, cough-relieving soft extract group.Each administration group is gastric infusion 20ml/kg according to dosage, and matched group gives the equal-volume distilled water, every day 1 time, 7d continuously.1h after the last administration takes off cervical vertebra and puts to death mice, wins and respectively organizes mouse thymus and spleen, in BA61 type electronic-weighing, calculates mouse thymus exponential sum index and spleen index.The results are shown in following table:
| Group | Dosage g crude drug/kg | Thymus index mg/g | Index and spleen index mg/g |
| Matched group | - | 1.256±0.381 | 3.369±0.540 |
| The KEKE JIAONANG group | 5.4 | 1.746±0.465 | 3.988±1.085 |
| Cough-relieving soft extract group | 5.4 | 1.886±0.407 | 4.159±0.844 |
Result and cough-relieving soft extract group mouse thymus index and index and spleen index are compared with matched group all apparently higher than the KEKE JIAONANG group, thymus index P＜0.01, index and spleen index P＜0.05.
This experiment shows: cough-relieving soft extract and KEKE JIAONANG relatively more can prolong the incubation period of strong aqua ammonia inducing mouse cough, increase rat expectoration amount, prolong the incubation period of Cavia porcellus asthma due to the histamine phosphate.In addition, the cough-relieving soft extract also has certain immunization.
Compared with prior art: preparation provided by the invention has the lung qi dispersing heat clearing away, cough-relieving, the effect of relievining asthma, and to upper respiratory tract infection, tracheitis, pneumonia, diseases such as cough have definite curative effect.The cough stopping formulation of routine is made soft extract, oral liquid or syrup, take, can play a multiplier effect in exsiccant season.Simultaneously soft extract also has the function of tonification, particularly asthma patient because of eipathia asthenia, but takes the soft extract health invigorating also with cough suppressing effect in the winter time, improves the immune disease-resistance ability of body, and recurrence helps warding off disease.Soft extract, oral liquid and syrup also provide the compliance that the patient takes this medicine in addition, and convenient child, old man, the patient that esophagus is narrower and small, gastrointestinal function is more weak take.Take disintegrate rapidly in tens seconds, dispersion behind the oral cavity disintegration tablet for the acute asthma patient, patient does not need water can obey smoothly down, directly the through port transmucosal absorbs, also can avoid the Degradation of first pass effect stomach function regulating, can play the effect that improves bioavailability.
The specific embodiment:
The embodiment of the invention 1: Herba Ephedrae 480g, Pericarpium Papaveris 480g, Radix Glycyrrhizae 480g, Semen Armeniacae Amarum 480g, Semen Raphani 150g, Radix Platycodonis 150g, Gypsum Fibrosum 150g, sucrose 23700g, tartaric acid 100g, sodium benzoate 8g
Herba Ephedrae, Pericarpium Papaveris are pulverized, and add the hydrochloric acid solution of 28800ml PH5, soak after 5 hours to decoct 10 times, all add the decoction 10 hours of the hydrochloric acid solution of 28800ml PH5 at every turn, filter, and merging filtrate, PH to 8.0 is standby for the medicinal liquid accent.Semen Armeniacae Amarum steamed 500 minutes earlier, and Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 27900ml water logging bubble 5 hours, decoct 10 times with Semen Armeniacae Amarum then, each decoction that all adds 42300ml water 10 hours filters filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes thick paste, gets sucrose, adds 47400ml water and is made into sucrose liquid and boils and dissolve, filter, tartarize is incubated 4 hours, makes it to become Nulomoline.Again above-mentioned gained thick paste is added in the Nulomoline, stir, boil, during relative density 1.65 during cryoconcentration to 60 ℃, add the sodium benzoate mixing, cold slightly, drag for floating foam, in time place canned bucket then, sealing is cooled to 80 ℃, promptly gets the cough-relieving soft extract.
The embodiment of the invention 2: Herba Ephedrae 480g, Pericarpium Papaveris 480g, Radix Glycyrrhizae 480g, Semen Armeniacae Amarum 480g, Semen Raphani 150g, Radix Platycodonis 150g, Gypsum Fibrosum 150g, sucrose 700g, sodium benzoate 8g, 1% chitin hydrochloric acid solution 100ml
Herba Ephedrae, Pericarpium Papaveris are pulverized, and add the hydrochloric acid solution of 28800ml PH5, soak after 5 hours to decoct 10 times, all add the decoction 10 hours of the hydrochloric acid solution of 28800ml PH5 at every turn, filter, and merging filtrate, PH to 8.0 is standby for the medicinal liquid accent.Semen Armeniacae Amarum steamed 500 minutes earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 27900ml water logging bubble 5 hours, decoct 10 times with Semen Armeniacae Amarum then, all add the decoction 10 hours of 42300ml water at every turn, filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, and concentrating under reduced pressure becomes thick paste, and other gets sucrose and adds and make dissolving in the water that boils evenly, filter, make simple syrup.Simple syrup is added in the said medicine filtrate, add sodium benzoate simultaneously.About heating in water bath to 70 ℃, keep this temperature, stir and add 1% chitin hydrochloric acid solution down, continue to stir 50min, filter.Get supernatant and add water to 1000ml, fill promptly gets the cough-relieving syrup.
The embodiment of the invention 3: Herba Ephedrae 480g, Pericarpium Papaveris 480g, Radix Glycyrrhizae 480g, Semen Armeniacae Amarum 480g, Semen Raphani 150g, Radix Platycodonis 150g, Gypsum Fibrosum 150g, sucrose 600g, sodium benzoate 8g
Herba Ephedrae, Pericarpium Papaveris are pulverized, and add the hydrochloric acid solution of 28800ml PH5, soak after 5 hours to decoct 10 times, all add the decoction 10 hours of the hydrochloric acid solution of 28800ml PH5 at every turn, filter, and merging filtrate, PH to 8.0 is standby for the medicinal liquid accent.Semen Armeniacae Amarum steamed 500 minutes earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 27900ml water logging bubble 5 hours, decoct 10 times with Semen Armeniacae Amarum then, each decoction that all adds 42300ml water 10 hours filters filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes thick paste, put cold after, adding ethanol is 90% to containing the alcohol amount.Left standstill 50 hours, and filtered, filtrate recycling ethanol continues to be condensed into thick paste, and it is an amount of to add water, and cold preservation 300 hours filters.Other gets sucrose and adds and to make dissolving in the water boil evenly, filters, and makes simple syrup.Simple syrup is added in the said medicine filtrate, add sodium benzoate simultaneously, boil dissolving, add water to 1000ml, transfer PH to 7 with sodium hydroxide, stir evenly, filter, embedding promptly gets the cough-relieving oral liquid.
The embodiment of the invention 4: Herba Ephedrae 480g, Pericarpium Papaveris 480g, Radix Glycyrrhizae 480g, Semen Armeniacae Amarum 480g, Semen Raphani 150g, Radix Platycodonis 150g, Gypsum Fibrosum 150g, low-substituted hydroxypropyl cellulose 100g, microcrystalline Cellulose 500g, sucrose 200g, Mentholum 100g
Herba Ephedrae, Pericarpium Papaveris are pulverized, and add the hydrochloric acid solution of 28800ml PH5, soak after 5 hours to decoct 10 times, all add the decoction 10 hours of the hydrochloric acid solution of 28800ml PH5 at every turn, filter, and merging filtrate, PH to 8.0 is standby for the medicinal liquid accent.Semen Armeniacae Amarum steamed 500 minutes earlier, and Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 27900ml water logging bubble 5 hours, decoct 10 times with Semen Armeniacae Amarum then, each decoction that all adds 42300ml water 10 hours, filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes extractum, drying is ground into 120 purpose powder, with low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, sucrose, Mentholum mix homogeneously, tabletting promptly gets the cough-relieving oral cavity disintegration tablet.
The embodiment of the invention 5: Herba Ephedrae 120g, Pericarpium Papaveris 120g, Radix Glycyrrhizae 120g, Semen Armeniacae Amarum 120g, Semen Raphani 37.5g, Radix Platycodonis 37.5g, Gypsum Fibrosum 37.5g, low-substituted hydroxypropyl cellulose 10g, microcrystalline Cellulose 10g, sucrose 20g, Mentholum 20g
Herba Ephedrae, Pericarpium Papaveris are pulverized, and add the hydrochloric acid solution of 720ml PH1, soak after 0.5 hour to decoct 0.5 hour, filter, and filtrate transfers PH to 6.0 standby.Semen Armeniacae Amarum steamed 5 minutes earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 697.5ml water logging bubble 0.5 hour, decoct 0.5 hour with Semen Armeniacae Amarum then, filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, and concentrating under reduced pressure becomes extractum, drying, be ground into 60 purpose powder, with low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, sucrose, Mentholum mix homogeneously, tabletting promptly gets the cough-relieving oral cavity disintegration tablet.
The embodiment of the invention 6: Herba Ephedrae 120g, Pericarpium Papaveris 120g, Radix Glycyrrhizae 120g, Semen Armeniacae Amarum 120g, Semen Raphani 37.5g, Radix Platycodonis 37.5g, Gypsum Fibrosum 37.5g, sucrose 15g, tartaric acid 0.1g, sodium benzoate 0.5g
Herba Ephedrae, Pericarpium Papaveris are pulverized, and add the hydrochloric acid solution of 720ml PH1, soak after 0.5 hour to decoct 0.5 hour, filter, and filtrate transfers PH to 6.0 standby.Semen Armeniacae Amarum steamed 5 minutes earlier, and Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 697.5ml water logging bubble 0.5 hour, decoct 0.5 hour with Semen Armeniacae Amarum then, filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, and concentrating under reduced pressure becomes thick paste, get sucrose, add 6ml water and be made into sucrose liquid and boil and dissolve, filter, add tartaric acid, be incubated 1 hour, make it to become Nulomoline.Again above-mentioned gained thick paste is added in the Nulomoline, stir, boil, during relative density 1.25 during cryoconcentration to 60 ℃, add the sodium benzoate mixing, cold slightly, drag for floating foam, in time place canned bucket then, sealing is cooled to 70 ℃, promptly gets the cough-relieving soft extract.
The embodiment of the invention 7: Herba Ephedrae 120g, Pericarpium Papaveris 120g, Radix Glycyrrhizae 120g, Semen Armeniacae Amarum 120g, Semen Raphani 37.5g, Radix Platycodonis 37.5g, Gypsum Fibrosum 37.5g, sucrose 200g, sodium benzoate 0.6g, 1% chitin hydrochloric acid solution 5ml
Herba Ephedrae, Pericarpium Papaveris are pulverized, and add the hydrochloric acid solution of 720ml PH1, soak after 0.5 hour to decoct 0.5 hour, filter, and filtrate transfers PH to 6.0 standby.Semen Armeniacae Amarum steamed 5 minutes earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 697.5ml water logging bubble 0.5 hour, decocted 0.5 hour with Semen Armeniacae Amarum then, filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes thick paste, other gets sucrose and adds and to make dissolving in the water boil evenly, filters, and makes simple syrup.Simple syrup is added in the said medicine filtrate, add sodium benzoate simultaneously.About heating in water bath to 35 ℃, keep this temperature, stir and add 1% chitin hydrochloric acid solution down, continue to stir 20min, filter.Get supernatant and add water to 1000ml, fill promptly gets the cough-relieving syrup.
The embodiment of the invention 8: Herba Ephedrae 120g, Pericarpium Papaveris 120g, Radix Glycyrrhizae 120g, Semen Armeniacae Amarum 120g, Semen Raphani 37.5g, Radix Platycodonis 37.5g, Gypsum Fibrosum 37.5g, sucrose 50g, sodium benzoate 0.6g
Herba Ephedrae, Pericarpium Papaveris are pulverized, and add the hydrochloric acid solution of 720ml PH1, soak after 0.5 hour to decoct 0.5 hour, filter, and filtrate transfers PH to 6.0 standby.Semen Armeniacae Amarum steamed 5 minutes earlier, and Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 697.5ml water logging bubble 0.5 hour, decoct 0.5 hour with Semen Armeniacae Amarum then, filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes thick paste, put cold after, adding ethanol is 40% to containing the alcohol amount.Left standstill 5 hours, and filtered, filtrate recycling ethanol continues to be condensed into thick paste, and it is an amount of to add water, and cold preservation 10 hours filters.Other gets sucrose and adds and to make dissolving in the water boil evenly, filters, and makes simple syrup.Simple syrup is added in the said medicine filtrate, add sodium benzoate simultaneously, boil dissolving, add water to 1000ml, transfer PH to 4 with sodium hydroxide, stir evenly, filter, embedding promptly gets the cough-relieving oral liquid.
The embodiment of the invention 9: Herba Ephedrae 240g, Pericarpium Papaveris 240g, Radix Glycyrrhizae 240g, Semen Armeniacae Amarum 240g, Semen Raphani 75g, Radix Platycodonis 75g, Gypsum Fibrosum 75g, sucrose 200g, sodium benzoate 3g
Herba Ephedrae, Pericarpium Papaveris are pulverized, and add the hydrochloric acid solution of 52800ml PH3, soak after 1 hour to decoct 2 times, and the hydrochloric acid solution that at every turn all adds 52800ml PH3 decocted 1.5 hours, filter, and merging filtrate, medicinal liquid transfer PH to 7.0 standby.Semen Armeniacae Amarum steamed 30 minutes earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 3720ml water logging bubble 1 hour, decoct 2 times with Semen Armeniacae Amarum then, each 4650ml decocting that adds boiled 2 hours, filtered filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes thick paste, put cold after, adding ethanol is 60% to containing the alcohol amount.Left standstill 18 hours, and filtered, filtrate recycling ethanol continues to be condensed into thick paste, and it is an amount of to add water, and cold preservation 72 hours filters.Other gets and makes dissolving in the water that sucrose goes into to boil evenly, filters, and makes simple syrup.Simple syrup is added in the said medicine filtrate, add sodium benzoate, boil dissolving, add water to 1000ml, transfer PH to 5.00-5.25 with sodium hydroxide, stir evenly, filter, embedding promptly gets the cough-relieving oral liquid.
The embodiment of the invention 10: Herba Ephedrae 240g, Pericarpium Papaveris 240g, Radix Glycyrrhizae 240g, Semen Armeniacae Amarum 240g, Semen Raphani 75g, Radix Platycodonis 75g, Gypsum Fibrosum 75g, low-substituted hydroxypropyl cellulose are 40g, and microcrystalline Cellulose is that 300g, sucrose are that 200g, Mentholum are 20g
Herba Ephedrae, Pericarpium Papaveris are pulverized, and add the hydrochloric acid solution of 52800ml PH3, soak after 1 hour to decoct 2 times, and the hydrochloric acid solution that at every turn all adds 52800ml PH3 decocted 1.5 hours, filter, and merging filtrate, medicinal liquid transfer PH to 7.0 standby.Semen Armeniacae Amarum steamed 30 minutes earlier, and Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 3720ml water logging bubble 1 hour, decoct 2 times with Semen Armeniacae Amarum then, each 4650ml decocting that adds boiled 2 hours, filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes extractum, drying is ground into 80 purpose powder, with low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, sucrose, Mentholum mix homogeneously, tabletting promptly gets the cough-relieving oral cavity disintegration tablet.
The embodiment of the invention 11: Herba Ephedrae 240g, Pericarpium Papaveris 240g, Radix Glycyrrhizae 240g, Semen Armeniacae Amarum 240g, Semen Raphani 75g, Radix Platycodonis 75g, Gypsum Fibrosum 75g, sucrose 500g, sodium benzoate 3g, 1% chitin hydrochloric acid solution 30ml
Herba Ephedrae, Pericarpium Papaveris are pulverized, and add the hydrochloric acid solution of 52800ml PH3, soak after 1 hour to decoct 2 times, and the hydrochloric acid solution that at every turn all adds 52800ml PH3 decocted 1.5 hours, filter, and merging filtrate, medicinal liquid transfer PH to 7.0 standby.Semen Armeniacae Amarum steamed 30 minutes earlier, and Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 3720ml water logging bubble 1 hour, decoct 2 times with Semen Armeniacae Amarum then, each 4650ml decocting that adds boiled 2 hours, filtered filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, and concentrating under reduced pressure becomes thick paste.Other gets sucrose and adds and to make dissolving in the water boil evenly, filters, and makes simple syrup.Simple syrup is added in the said medicine filtrate, add sodium benzoate simultaneously.About heating in water bath to 45 ℃, keep this temperature, stir and add 1% chitin hydrochloric acid solution down, continue to stir 20min, filter.Get supernatant and add water to 1000ml, fill promptly gets the cough-relieving syrup.
The embodiment of the invention 12: Herba Ephedrae 240g, Pericarpium Papaveris 240g, Radix Glycyrrhizae 240g, Semen Armeniacae Amarum 240g, Semen Raphani 75g, Radix Platycodonis 75g, Gypsum Fibrosum 75g, sucrose 500g, tartaric acid 1g, sodium benzoate 2g
Herba Ephedrae, Pericarpium Papaveris are pulverized, and add the hydrochloric acid solution of 52800ml PH3, soak after 1 hour to decoct 2 times, and the hydrochloric acid solution that at every turn all adds 52800ml PH3 decocted 1.5 hours, filter, and merging filtrate, medicinal liquid transfer PH to 7.0 standby.Semen Armeniacae Amarum steamed 30 minutes earlier, and Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 3720ml water logging bubble 1 hour, decoct 2 times with Semen Armeniacae Amarum then, each 4650ml decocting that adds boiled 2 hours, filtered filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, and concentrating under reduced pressure becomes thick paste.Get sucrose, add 500ml water and be made into sucrose liquid and boil and dissolve, filter, add 0.1% tartaric acid, be incubated 2 hours, make it to become Nulomoline.Again above-mentioned gained thick paste is added in the Nulomoline, stir, boil, relative density 1.40～1.45 during cryoconcentration to 60 ℃ o'clock, add the sodium benzoate mixing, cold slightly, drag for floating foam, in time place canned bucket then, sealing is cooled to 70～80 ℃, promptly gets the cough-relieving soft extract.
Claims (10)
1. cough stopping formulation, it is characterized in that: calculate according to composition by weight: it mainly is prepared into soft extract, oral liquid, syrup or oral disintegrating tablet formulation by Herba Ephedrae 120-480, Pericarpium Papaveris 120-480, Radix Glycyrrhizae 120-480, Semen Armeniacae Amarum 120-480, Semen Raphani 37.5-150, Radix Platycodonis 37.5-150, Gypsum Fibrosum 37.5-150.
2. according to the described cough stopping formulation of claim 1, it is characterized in that: it mainly is prepared into soft extract, oral liquid, syrup or oral disintegrating tablet formulation by Herba Ephedrae 240, Pericarpium Papaveris 240, Radix Glycyrrhizae 240, Semen Armeniacae Amarum 240, Semen Raphani 75, Radix Platycodonis 75, Gypsum Fibrosum 75.
3. the preparation method of cough stopping formulation as claimed in claim 1 or 2, it is characterized in that: Herba Ephedrae, Pericarpium Papaveris is pulverized the back and is extracted with semi-biomimetic method, and Semen Armeniacae Amarum steams earlier, and Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum are soaked, Semen Armeniacae Amarum water decocting method extraction together then, with Herba Ephedrae, the Pericarpium Papaveris extracting solution merges behind the extracting liquid filtering, and concentrating under reduced pressure becomes extractum, add different adjuvants again, can make different preparations with conventional method.
4. according to the preparation method of the described cough stopping formulation of claim 3, it is characterized in that: concrete preparation technology is: Herba Ephedrae, Pericarpium Papaveris are pulverized, add 3-30 and doubly measure the hydrochloric acid solution that PH is 1-5, soak after 0.5-5 hour and decoct 1-10 time, the PH that each 3-30 of adding doubly measures is that the hydrochloric acid solution of 1-5 decocted 0.5-10 hour, filter, merging filtrate, medicinal liquid transfer PH to 6.0-8.0 standby; Semen Armeniacae Amarum steamed 5-500 minute earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum add 3-30 times of water gaging and soaked 0.5-5 hour, decoct 1-10 time with Semen Armeniacae Amarum then, the decocting that each adding 3-30 doubly measures boiled 0.5-10 hour, filtered filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes extractum, adds different adjuvants again, makes soft extract preparation, oral liquid, syrup or oral disintegrating tablet formulation with conventional method.
5. according to the preparation method of claim 3 or 4 described cough stopping formulations, it is characterized in that: the technology when the present invention makes soft extract is: Herba Ephedrae, Pericarpium Papaveris are pulverized, adding 3-30 doubly measures the hydrochloric acid solution of PH1-5, soak after 0.5-5 hour and decoct 1-10 time, the hydrochloric acid solution of the PH1-5 that each 3-30 of adding doubly measures decocted 0.5-10 hour, filter, merging filtrate, medicinal liquid transfer PH to 6.0-8.0 standby; Semen Armeniacae Amarum steamed 5-500 minute earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum adds 3-30 times of water gaging and soaked 0.5-5 hour, decocts 1-10 time with Semen Armeniacae Amarum then, adds the decocting that 3-30 doubly measures at every turn and boils 0.5-10 hour, filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, and concentrating under reduced pressure becomes thick paste, take by weighing the sucrose that thick paste 0.1-10 doubly measures, add the water of sucrose amount 40% or more and be made into sucrose liquid and boil and dissolve, filter the tartaric acid of adding 0.01-10%, insulation is more than 1 hour, make it to become Nulomoline, more above-mentioned gained thick paste is added in the Nulomoline, stir, boil, relative density 1.25～1.65 during cryoconcentration to 60 ℃ o'clock add 0.05%-0.8% sodium benzoate mixing, and are cold slightly, drag for floating foam, in time place canned bucket then, sealing is cooled to 70～80 ℃, promptly gets the soft extract preparation.
6. according to the preparation method of the described cough stopping formulation of claim 5, it is characterized in that: adjuvant used when making soft extract can be: one or more mixing wherein of sodium benzoate, benzoic acid, nipalgin or potassium sorbate.
7. according to the preparation method of claim 3 or 4 described cough stopping formulations, it is characterized in that: the technology when the present invention makes oral liquid is: Herba Ephedrae, Pericarpium Papaveris are pulverized, adding 3-30 doubly measures the hydrochloric acid solution of PH1-5, soak after 0.5-5 hour and decoct 1-10 time, the hydrochloric acid solution of the PH1-5 that each 3-30 of adding doubly measures decocted 0.5-10 hour, filter, merging filtrate, medicinal liquid transfer PH to 6.0-8.0 standby; Semen Armeniacae Amarum steamed 5-500 minute earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum adds 3-30 times of water gaging and soaked 0.5-5 hour, decocts 1-10 time with Semen Armeniacae Amarum then, the decocting that each adding 3-30 doubly measures boiled 0.5-10 hour, filtered filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, and concentrating under reduced pressure becomes thick paste, put cold after, add ethanol to containing the alcohol amount, left standstill 5-50 hour, filter for 40-90%, filtrate recycling ethanol continues to be condensed into thick paste, and it is an amount of to add water, cold preservation 10-300 hour, filter, other gets in the water that an amount of sucrose goes into to boil and makes dissolving evenly, filters, make simple syrup, with making final sugar content 5-60% in an amount of simple syrup adding said medicine filtrate, add the 0.06%-0.8% sodium benzoate, boil dissolving, add water to full dose, transfer PH to 4-7 with sodium hydroxide, stir evenly, filter, embedding, promptly.
8. according to the preparation method of the described cough stopping formulation of claim 7, it is characterized in that: adjuvant used when making oral liquid is: one or more mixing wherein of sodium benzoate, benzoic acid, nipalgin or potassium sorbate.
9. according to the preparation method of claim 3 or 4 described cough stopping formulations, it is characterized in that: the technology when the present invention makes syrup is: Herba Ephedrae, Pericarpium Papaveris is pulverized, adding 3-30 doubly measures the hydrochloric acid solution of PH1-5, soak after 0.5-5 hour and decoct 1-10 time, the hydrochloric acid solution of the PH1-5 that each 3-30 of adding doubly measures decocted 0.5-10 hour, filter, merging filtrate, medicinal liquid transfers PH to 6.0-8.0 standby, Semen Armeniacae Amarum steamed 5-500 minute earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum adds 3-30 times of water gaging and soaked 0.5-5 hour, decocts 1-10 time with Semen Armeniacae Amarum then, adds the decocting that 3-30 doubly measures at every turn and boils 0.5-10 hour, filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, and concentrating under reduced pressure becomes thick paste.Other gets an amount of sucrose and adds and make dissolving in the water that boils evenly, filters, and makes simple syrup.To make final sugar content 20-70% in an amount of simple syrup adding said medicine filtrate, add the 0.06%-0.8% sodium benzoate simultaneously, heating in water bath is to about 35-70 ℃, keep this temperature, stir the 1% chitin hydrochloric acid solution that adds the 0.5-10% volume down, continue to stir 10-60min, filter, get supernatant and add water to full dose, fill, promptly.
10. according to the preparation method of claim 3 or 4 described cough stopping formulations, it is characterized in that: the technology when the present invention makes oral cavity disintegration tablet is: Herba Ephedrae, Pericarpium Papaveris is pulverized, adding 3-30 doubly measures the hydrochloric acid solution of PH1-5, soak after 0.5-5 hour and decoct 1-10 time, the hydrochloric acid solution of the PH1-5 that each 3-30 of adding doubly measures decocted 0.5-10 hour, filter, merging filtrate, medicinal liquid transfers PH to 6.0-8.0 standby, Semen Armeniacae Amarum steamed 5-500 minute earlier, Radix Glycyrrhizae, Semen Raphani, Radix Platycodonis, Gypsum Fibrosum adds 3-30 times of water gaging and soaked 0.5-5 hour, decocts 1-10 time with Semen Armeniacae Amarum then, the decocting that each adding 3-30 doubly measures boiled 0.5-10 hour, filter, filtrate and Herba Ephedrae, the Pericarpium Papaveris extracting solution merges, concentrating under reduced pressure becomes extractum, drying is ground into the above powder of 60 orders, with the low-substituted hydroxypropyl cellulose of 1-10%, the 10-50% microcrystalline Cellulose, 2-20% sucrose, 2-10% Mentholum mix homogeneously, tabletting promptly gets oral cavity disintegration tablet; Used adjuvant can also be the mixture of one or more in cross-linked carboxymethyl cellulose sodium, crospolyvinylpyrrolidone, crosslinked carboxymethylstach sodium, the erythrol.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410155496 CN1631429A (en) | 2004-12-02 | 2004-12-02 | Cough stopping formulation and its preparing processes |
| CNB2005102004830A CN100415209C (en) | 2004-12-02 | 2005-08-19 | Cough stopping preparation and process for preparing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410155496 CN1631429A (en) | 2004-12-02 | 2004-12-02 | Cough stopping formulation and its preparing processes |
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| Publication Number | Publication Date |
|---|---|
| CN1631429A true CN1631429A (en) | 2005-06-29 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410155496 Pending CN1631429A (en) | 2004-12-02 | 2004-12-02 | Cough stopping formulation and its preparing processes |
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| Country | Link |
|---|---|
| CN (1) | CN1631429A (en) |
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- 2004-12-02 CN CN 200410155496 patent/CN1631429A/en active Pending
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