CN103191116A - Dextromethorphan hydrobromide and guaiacol glycerin ether oral liquid and preparation method thereof - Google Patents
Dextromethorphan hydrobromide and guaiacol glycerin ether oral liquid and preparation method thereof Download PDFInfo
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- CN103191116A CN103191116A CN2013101260321A CN201310126032A CN103191116A CN 103191116 A CN103191116 A CN 103191116A CN 2013101260321 A CN2013101260321 A CN 2013101260321A CN 201310126032 A CN201310126032 A CN 201310126032A CN 103191116 A CN103191116 A CN 103191116A
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Abstract
The invention discloses a dextromethorphan hydrobromide and guaiacol glycerin ether oral liquid. The oral liquid contains dextromethorphan hydrobromide, guaiacol glycerin ether, acidifying and alkalizing agents and purified water, wherein the acidifying and alkalizing agents are used for regulating the pH value of the dextromethorphan hydrobromide and guaiacol glycerin ether oral liquid to be 4.0-5.5.
Description
Technical field
The invention belongs to field of medicine preparations, be specifically related to a kind of dextromethorphan hydrobromide guaifenesin oral liquid and preparation method thereof.
Background technology
Flu is equal generable common respiratory tract diseases of a kind of four seasons, is caused by multiple virus or pathogenic bacteria, as untimely treatment, can cause many complication, as pneumonia, myocarditis etc., brings serious harm for people's health.Bronchitis is old people's commonly encountered diseases in the winter time, and according to statistics, the sickness rate of China's middle-aged and elderly people more than 50 years old is 15-30%.Respiratory tract infection and bronchitic clinical symptoms have cough, expectoration, have a strong impact on the normal work of people and life.
Dextromethorphan hydrobromide is central antitussive, can suppress the medulla oblongata coughing centre and produces antitussive effect.Its antitussive effect equates with codeine or is strong slightly that therapeutic dose does not suppress to breathe, and takes no addiction and toleration for a long time.Guaifenesin is expectorant, and the respiratory tract glandular secretion is increased, and sputum is diluted, and is easy to expectoration, thereby produces phlegm-dispelling functions.Dextromethorphan hydrobromide and guaifenesin have good synergism, become compound preparation to be used for the treatment of cough, expectoration that upper respiratory tract infection, bronchitis cause both compatibilities.
The compound preparation of dextromethorphan hydrobromide and guaifenesin mainly comprises tablet, slow releasing tablet and solution (syrup) both at home and abroad at present.Wherein solution is because patient's taking convenience, mouthfeel is good, drug effect is fast etc., and advantage is occupied critical role in dosage form, but solution Chinese medicine poor stability is the important step that influences the solution quality.
The dextromethorphan hydrobromide guaifenesin solution of listing is dextromethorphan hydrobromide guaifenesin syrup (trade name: Shi Dagong and trade name: U.S. can be graceful) both at home and abroad.Fig. 2 is that the accelerated stability that Shi Dagong, U.S. can graceful syrup is investigated resulting figure as a result.
As shown in Figure 2, history is reached merit and the graceful syrup of Mei Ke is researched and analysed, its pH condition is respectively at pH5.8 and pH3.4, and all there is 1-2 content in these two kinds of syrups through study on the stability〉0.5% impurity.The impurity content height is unfavorable for drug quality control, can increase the occurrence risk of untoward reaction simultaneously.
The investigation result of accelerated test shows that the medicine that gone on the market (name of an article history reaches merit and Mei Ke is graceful) medicine stability is not good, accelerates to investigate through 6 months, and medicament contg descends, and impurity (related substance) rises.
In addition, apply for a patent CN102600210A and disclose a kind of compound recipe DM Cough agent and preparation method thereof, in this syrup, add the Bacillus natto extract, reduce the application of antiseptic, aromatic, improve colour stability; Apply for a patent CN102283840A and disclose a kind of granule that contains dextromethorphan hydrobromide and guaifenesin and preparation method thereof, make dextromethorphan hydrobromide-hydroxypropyl-beta-cyclodextrin inclusion, improve medicine stability, the big problem of dextromethorphan hydrobromide blood concentration fluctuation after the solution administration; Patent CN1628667A discloses compound dried suspension of a kind of dextromethorphan hydrobromide and guaifenesin and preparation method thereof, solves drug dissolution and mouthfeel, is fit to children.Yet above-mentioned apply for a patent or patent of invention all less than solving the medicine stability how to improve dextromethorphan hydrobromide guaifenesin solution.
Summary of the invention
In order to solve the medicine stability problem that improves dextromethorphan hydrobromide guaifenesin solution, the invention provides a kind of dextromethorphan hydrobromide guaifenesin oral liquid and preparation method thereof, by selecting proper supplementary material and regulating pH value in the preparation process, resulting dextromethorphan hydrobromide guaifenesin oral liquid impurity content is low, quality is easy to control, and is safe.
In order to reach above purpose, the present invention has adopted following technical scheme:
A kind of dextromethorphan hydrobromide guaifenesin oral liquid, contain dextromethorphan hydrobromide, guaifenesin, acid-base modifier, purified water, it is characterized in that: acid-base modifier is regulated the pH value of dextromethorphan hydrobromide guaifenesin oral liquid in the 4.0-5.5 scope.
Further, dextromethorphan hydrobromide guaifenesin oral liquid of the present invention can also have such feature: acid-base modifier is regulated the pH value of dextromethorphan hydrobromide guaifenesin oral liquid in the 4.4-4.8 scope.
Further, dextromethorphan hydrobromide guaifenesin oral liquid of the present invention can also have such feature: the pH value that acid-base modifier is regulated dextromethorphan hydrobromide guaifenesin oral liquid is 4.8.
Further, dextromethorphan hydrobromide guaifenesin oral liquid of the present invention can also have such feature: also contain correctives, antiseptic, pigment, essence.
Further, dextromethorphan hydrobromide guaifenesin oral liquid of the present invention can also have such feature: acid-base modifier is any one or a few the combination in hydrochloric acid solution, acetum, phosphoric acid solution, potassium dihydrogen phosphate, sodium dihydrogen phosphate, citric acid solution, sodium citrate solution, ammonia spirit, sodium hydroxide solution, the potassium hydroxide solution.
Further, dextromethorphan hydrobromide guaifenesin oral liquid of the present invention can also have such feature: acid-base modifier is citric acid solution or sodium citrate solution.
Further, dextromethorphan hydrobromide guaifenesin oral liquid of the present invention, can also have such feature: correctives is sucrose, steviosin, sucralose, the combination of any one or a few in the acesulfame potassium, antiseptic is benzoic acid, sodium benzoate, methyl hydroxybenzoate, ethyl hydroxybenzoate, the combination of any one or a few in oxybenzene third fat, pigment is carmine, lemon yellow, the combination of any one or a few in the sunset yellow, essence are black currant essence, Herba Menthae essence, flavoring orange essence, tutti fruit essence, strawberry essence, the combination of any one or a few in the flavoring banana essence.
Further, dextromethorphan hydrobromide guaifenesin oral liquid of the present invention, can also have such feature: the concentration of dextromethorphan hydrobromide is 1.5g/L, the concentration of guaifenesin is 10g/L, concentration of sucrose is 450g/L, the concentration of sodium benzoate is 1g/L, the concentration of methyl hydroxybenzoate is 1.5g/L, the concentration of black currant essence is 2g/L, the concentration of carmine is 6mg/L, the pH value of dextromethorphan hydrobromide guaifenesin oral liquid is in the 4.6-4.8 scope, and acid-base modifier is that concentration is the citric acid solution of 1-2mol/L, in the sodium citrate solution any one.
In addition, the present invention also provides a kind of method for preparing dextromethorphan hydrobromide guaifenesin oral liquid, it is characterized in that, may further comprise the steps: a certain amount of correctives is dissolved in the purified water, after stirring and dissolving, then add a certain amount of active carbon, and stir 10min, by removing by filter active carbon, obtain solution one again; A certain amount of dextromethorphan hydrobromide, guaifenesin, antiseptic, essence and pigment are added stirring and dissolving in the solution one, obtain solution two; Adopt acid-base modifier that the pH value of solution two is adjusted in the 4.6-4.8 scope, obtain solution three; The purified water of certain volume is added solution three, obtain solution four; Solution four is filtered, pass through flowing steam sterilization again, then fill obtains dextromethorphan hydrobromide guaifenesin oral liquid, wherein, correctives is sucrose, antiseptic is sodium benzoate, methyl hydroxybenzoate, essence is black currant essence, pigment is carmine, the mass ratio of dextromethorphan hydrobromide and guaifenesin is 1.5:10, dextromethorphan hydrobromide, sucrose, active carbon, sodium benzoate, methyl hydroxybenzoate, black currant essence, the mass ratio of carmine is 1.5:450:1:1:1.5:2:0.006, and in solution four, the concentration of dextromethorphan hydrobromide is 1.5g/L.
Effect and the effect of invention
According to dextromethorphan hydrobromide guaifenesin oral liquid provided by the invention, by the adjuvant of in preparation process, selecting to be fit to, i.e. correctives, antiseptic, pigment, essence, and regulate its pH value, final resulting oral liquid impurity is few, and stabilised quality is safe.
Description of drawings
Fig. 1 is the liquid chromatograph sketch map of the dextromethorphan hydrobromide guaifenesin oral liquid sample among the embodiment;
Fig. 2 is that the accelerated stability that Shi Dagong, U.S. can graceful syrup is investigated resulting figure as a result;
Fig. 3 is the figure as a result that carries out influence factor's test under the condition of 3-7 in the pH scope for the dextromethorphan hydrobromide among the embodiment;
Fig. 4 is the figure as a result that carries out influence factor's test under the condition of 3-7 in the pH scope for the guaifenesin among the embodiment;
Fig. 5 is the figure as a result that carries out influence factor's test under the condition of 4.0-5.5 in the pH scope for the dextromethorphan hydrobromide among the embodiment;
Fig. 6 is the figure as a result that carries out influence factor's test under the condition of 4.0-5.5 in the pH scope for the guaifenesin among the embodiment;
Fig. 7 is the figure as a result that carries out influence factor's test under the condition of 4.2-5.2 in the pH scope for the mixture of the dextromethorphan hydrobromide guaifenesin among the embodiment;
The figure as a result that Fig. 8 carries out influence factor's test when adding different auxiliary material for the dextromethorphan hydrobromide among the embodiment and guaifenesin under pH is 4.73 condition;
Fig. 9 is that the dextromethorphan hydrobromide guaifenesin oral liquid among the embodiment carries out the figure as a result in influence factor's test and the accelerated stability investigation test.
The specific embodiment
The present invention will be described in detail below in conjunction with specific embodiment.
The medicament contg of the dextromethorphan hydrobromide guaifenesin oral liquid in the present embodiment, related substance physicochemical properties such as (impurity) adopt liquid chromatography to measure.Fig. 1 is the liquid chromatograph sketch map of the dextromethorphan hydrobromide guaifenesin oral liquid sample among the embodiment.
Condition determination and the parameter of liquid chromatography are as follows:
Chromatographic condition: welchrom-C18 chromatographic column (250 mm * 4.6 mm, 5 μ m);
Mobile phase: methanol-2.5mmol/L perfluoroetane sulfonic acid sodium solution-acetic acid (500:498:2), acetic acid transfers to pH(3.0 ± 0.1), detect wavelength 280 nm; Flow velocity 1.0 ml/min; Sample size 20 μ l.
Theoretical cam curve should be not less than 2000 by dextromethorphan hydrobromide, guaifenesin peak, the separating degree of main peak and adjacent impurity peaks＞1.5.
The assay process of dextromethorphan hydrobromide and guaifenesin is as follows in the test sample:
Get an amount of oral liquid sample and (be equivalent to contain hydrobromic acid dextromethorphan 7.5mg approximately, guaifenesin 50mg), place the 100ml measuring bottle, adding mobile phase is diluted to 100ml with sample solution and shakes up, then the accurate 20 μ l of measuring dilute good sample solution injection chromatograph of liquid, test and record test sample chromatogram;
In addition, precision takes by weighing dextromethorphan hydrobromide and guaifenesin reference substance each is an amount of respectively, place same measuring bottle, add an amount of methanol, make the dextromethorphan hydrobromide dissolving, add water then and make the solution that contains hydrobromic acid dextromethorphan 75 μ g, guaifenesin 500 μ g among every 1ml approximately, measure the reference substance spectrogram with method.
Calculate the content of dextromethorphan hydrobromide and guaifenesin in the test sample respectively with peak area by external standard method.
Related substance in the test sample (impurity) assay process is as follows:
Sample thief an amount of (being equivalent to dextromethorphan hydrobromide 7.5mg approximately, guaifenesin 50mg) places 50 ml measuring bottles, is diluted to scale with mobile phase, shakes up, and filters, and obtains need testing solution;
Pipette need testing solution 1ml and place the 100ml measuring bottle, add mobile phase and be diluted to scale, shake up, filter, obtain contrast solution;
Accurately measure each 20 μ l of above-mentioned solution, measure by above-mentioned chromatographic condition sample introduction;
In the chromatogram of need testing solution as impurity peaks (deduction system solvent peak, adjuvant peak) occurs, measure each impurity peaks peak area sum, with it with the reference substance solution peak area ratio, obtain related substance (impurity) content.
Embodiment one
Present embodiment provide dextromethorphan hydrobromide and the medicine stability of guaifenesin under different pH value with and employed supplementary material Study on Compatibility.
Below be dextromethorphan hydrobromide and the medicine stability research of guaifenesin under different pH value.
Fig. 3 is the figure as a result that carries out influence factor's test under the condition of 3-7 in the pH scope for the dextromethorphan hydrobromide among the embodiment, Fig. 4 is the figure as a result that carries out influence factor's test under the condition of 3-7 in the pH scope for the guaifenesin among the embodiment, Fig. 5 is the figure as a result that carries out influence factor's test under the condition of 4.0-5.5 in the pH scope for the dextromethorphan hydrobromide among the embodiment, Fig. 6 is the figure as a result that carries out influence factor's test under the condition of 4.0-5.5 in the pH scope for the guaifenesin among the embodiment, and Fig. 7 is the figure as a result that carries out influence factor's test under the condition of 4.2-5.2 in the pH scope for the mixture of the dextromethorphan hydrobromide guaifenesin among the embodiment.
450g sucrose is dissolved in the 800ml purified water after the stirring and dissolving, then adds the 1g active carbon and stir 10min, by removing by filter active carbon, obtain solution one again; 1.5g dextromethorphan hydrobromide, 10g guaifenesin, 1g sodium benzoate, 1.5g methyl hydroxybenzoate, 2g black currant essence, 6mg carmine are added stirring and dissolving in the solution one, obtain solution two; Adopt citric acid/sodium citrate solution that solution two pH value are adjusted to different pH value, obtain solution three; Purified water is added solution three reach 1000ml until volume, obtain sample solution.
Sample solution is placed on carries out influence factor's test that 60 ℃ of high temperature, intensity of illumination are 4500 strong illuminations of reining in 60 ℃ of low temperature and irradiance instrument in the water isolation type constant incubator respectively, sampling during respectively at 0,5,10 day, adopt liquid chromatography to carry out the test of medicament contg and related substance (impurity) content, its test result such as Fig. 3-shown in Figure 7.
It below is the employed supplementary material Study on Compatibility of dextromethorphan hydrobromide and guaifenesin oral liquid.
The figure as a result that Fig. 8 carries out influence factor's test when adding different auxiliary material for the dextromethorphan hydrobromide among the embodiment and guaifenesin under pH is 4.73 condition.
A sample solution quality proportioning:
Dextromethorphan hydrobromide: guaifenesin: sucrose=1.5:10:450;
No. two sample solution quality proportionings:
Dextromethorphan hydrobromide: guaifenesin: sodium benzoate=1.5:10:1;
No. three sample solution quality proportionings:
Dextromethorphan hydrobromide: guaifenesin: methyl hydroxybenzoate=1.5:10:1.5;
No. four sample solution quality proportionings:
Dextromethorphan hydrobromide: guaifenesin: aspartame=1.5:10:5;
No. five sample solution quality proportionings:
Dextromethorphan hydrobromide: guaifenesin: steviosin=1.5:10:4.5.
Above five sample solutions are placed on carry out influence factor's test that 60 ℃ of high temperature, intensity of illumination are 4500 strong illuminations of reining in 60 ℃ of low temperature and irradiance instrument in the water isolation type constant incubator respectively, sampling during respectively at 0,5,10 day, adopt liquid chromatography to carry out the test of medicament contg and related substance (impurity) content, its test result as shown in Figure 8.
The effect of embodiment one and effect
Result of the test that present embodiment one provides shows that the medicine dextromethorphan hydrobromide is more stable in pH value is in the 4-5.5 scope, in that to carry out producing impurity level when the influence factor tests less, when pH=7, is carrying out producing more impurity when the influence factor tests; The medicine guaifenesin is more stable in pH value is in the 4.5-7 scope, when pH value less than 4 the time, carrying out then producing more impurity when the influence factor tests.So the compound preparation of dextromethorphan hydrobromide and guaifenesin must be selected suitable pH scope, make both all obtain stability preferably.Therefore the pH scope that can select of compound preparation is 4.0-5.5, and it is more stable in pH value is in the 4.4-4.8 scope, and the impurity of generation further reduces, and the impurity level that produces when pH=4.8 is minimum.
Embodiment two
Adopt following formulation 1000mL dextromethorphan hydrobromide guaifenesin oral liquid in the present embodiment:
2N hydrochloric acid or sodium hydroxide solution are adjusted to the solution pH value in the 4.0-5.5 scope, and all the other are purified water.
The dextromethorphan hydrobromide guaifenesin oral liquid preparation process of present embodiment is as follows:
4.5g steviosin, 1.5g dextromethorphan hydrobromide, 10g guaifenesin, 1.5g methyl hydroxybenzoate, 1.5g ethyl hydroxybenzoate, 2g Herba Menthae essence, 6mg sunset yellow are dissolved in the 800ml purified water after the stirring and dissolving, then add the 1g active carbon and stir 10min, by removing by filter active carbon, obtain solution one again;
Adopt 2N hydrochloric acid solution or sodium hydroxide solution that solution one pH value is adjusted in the 4.0-5.5 scope, obtain solution two;
Purified water is added solution two reach 1000ml until volume, obtain solution three;
Filtering solution three passes through flowing steam sterilization again, and then fill obtains dextromethorphan hydrobromide guaifenesin oral liquid.
The effect of embodiment two and effect
The dextromethorphan hydrobromide guaifenesin oral liquid formulations that present embodiment two provides has effect and the effect of embodiment one, and present embodiment two is in preparation process, adopt 2N hydrochloric acid solution or sodium hydroxide solution as acid-base modifier, adopt steviosin as correctives, adopt methyl hydroxybenzoate and ethyl hydroxybenzoate as antiseptic, adopt Herba Menthae essence as essence, adopt sunset yellow as pigment, the solution pH value is in the 4.0-5.5 scope, has prepared dextromethorphan hydrobromide guaifenesin oral liquid.
Embodiment three
Adopt following formulation 1000mL dextromethorphan hydrobromide guaifenesin oral liquid in the present embodiment:
2N hydrochloric acid solution or sodium hydroxide solution are adjusted to pH value of solution in the 4.0-5.5 scope, and all the other are purified water.
The dextromethorphan hydrobromide guaifenesin oral liquid preparation process of present embodiment is as follows:
3.0g sucralose, 1.5g dextromethorphan hydrobromide, 10g guaifenesin, 1.5g methyl hydroxybenzoate, 1.5g ethyl hydroxybenzoate, 2g flavoring orange essence, 6mg lemon yellow are dissolved in the 800ml purified water after the stirring and dissolving, then add the 1g active carbon and stir 10min, by removing by filter active carbon, obtain solution one again;
Adopt 2N hydrochloric acid solution or sodium hydroxide solution that solution one pH value is adjusted in the 4.0-5.5 scope, obtain solution two;
Purified water is added solution two reach 1000ml until volume, obtain solution three;
Filtering solution three passes through flowing steam sterilization again, and then fill obtains dextromethorphan hydrobromide guaifenesin oral liquid.
The effect of embodiment three and effect
The dextromethorphan hydrobromide guaifenesin oral liquid formulations that present embodiment three provides has effect and the effect of embodiment one, and present embodiment three is in preparation process, adopt 2N hydrochloric acid solution or sodium hydroxide solution as acid-base modifier, adopt sucralose as correctives, adopt methyl hydroxybenzoate and ethyl hydroxybenzoate as antiseptic, adopt flavoring orange essence as essence, adopt lemon yellow as pigment, the solution pH value is in the 4.0-5.5 scope, prepares dextromethorphan hydrobromide guaifenesin oral liquid.
Embodiment four
Adopt following formulation 1000mL dextromethorphan hydrobromide guaifenesin oral liquid in the present embodiment:
To the 4.6-4.8 scope, all the other are purified water with the pH regulator of sample solution for citric acid or sodium citrate solution.
The dextromethorphan hydrobromide guaifenesin oral liquid preparation process of present embodiment is as follows:
450g sucrose is dissolved in the 800ml purified water after the stirring and dissolving, then adds the 1g active carbon and stir 10min, by removing by filter active carbon, obtain solution one again;
1.5g dextromethorphan hydrobromide, 10g guaifenesin, 1g sodium benzoate, 1.5g methyl hydroxybenzoate, 2g black currant essence, 6mg carmine are added stirring and dissolving in the solution one, obtain solution two;
Adopt citric acid or sodium citrate solution that solution two pH value are adjusted in the 4.6-4.8 scope, obtain solution three;
Purified water is added solution three reach 1000ml until volume, obtain solution four;
Filtering solution four passes through flowing steam sterilization again, and then fill obtains dextromethorphan hydrobromide guaifenesin oral liquid.
Fig. 9 is that the dextromethorphan hydrobromide guaifenesin oral liquid among the embodiment carries out the figure as a result in influence factor's test and the accelerated stability investigation test.
The dextromethorphan hydrobromide guaifenesin oral liquid that present embodiment is made carries out temperatures involved factor (60 ℃) and strong illumination (light intensity be 4500 rein in) test, respectively at sampling in 0,5,10 day, carry out 6 months accelerated stabilities simultaneously and investigate (40 ℃, RH75%), detect the content of each component, the result as shown in Figure 9.Comparison diagram 2 and Fig. 9, can draw, dextromethorphan hydrobromide guaifenesin oral liquid, Shi Dagong and the Mei Ke that present embodiment makes is graceful very approaching at 0 o'clock dextromethorphan hydrobromide and guaifenesin content constantly, and after investigating through 6 months accelerated stabilities, the dextromethorphan hydrobromide guaifenesin oral liquid Chinese medicine dextromethorphan hydrobromide content that present embodiment makes is 98.84%, and medicine guaifenesin content is 99.16%.And the medicine dextromethorphan hydrobromide content of Shi Dagong is 96.21%, medicine guaifenesin content is 97.33%, beautiful medicine dextromethorphan hydrobromide content that can be graceful is 95.68%, medicine guaifenesin content is 96.35%, so the medicine stability of the dextromethorphan hydrobromide guaifenesin oral liquid that makes of present embodiment is improved.
The effect of embodiment four and effect
The dextromethorphan hydrobromide guaifenesin oral liquid formulations that present embodiment four provides has effect and the effect of embodiment one, and present embodiment two is in preparation process, adopt citric acid solution or sodium citrate solution as acid-base modifier, adopt sucrose as correctives, adopt methyl hydroxybenzoate and sodium benzoate as antiseptic, adopt black currant essence as essence, adopt carmine as pigment, the solution pH value is in the 4.6-4.8 scope, has prepared dextromethorphan hydrobromide guaifenesin oral liquid.
The dextromethorphan hydrobromide guaifenesin oral liquid formulations that present embodiment four provides not only has effect and the effect of embodiment one, also has steady quality, and impurity is few, safe characteristics.Dextromethorphan hydrobromide guaifenesin oral liquid, Shi Dagong and the Mei Ke that present embodiment four makes is graceful very approaching at 0 o'clock dextromethorphan hydrobromide and guaifenesin content constantly, and after investigating through 6 months accelerated stabilities, the dextromethorphan hydrobromide guaifenesin oral liquid Chinese medicine dextromethorphan hydrobromide content that present embodiment makes is 98.84, and medicine guaifenesin content is 99.16%.And the medicine dextromethorphan hydrobromide content of Shi Dagong is 96.21%, medicine guaifenesin content is 97.33%, beautiful medicine dextromethorphan hydrobromide content that can be graceful is 95.68%, medicine guaifenesin content is 96.35%, therefore the medicine stability of the dextromethorphan hydrobromide guaifenesin oral liquid that makes of present embodiment is improved, and illustrate that selection proper supplementary material and pH scope help to improve stability of drug.
Certainly, oral liquid involved in the present invention not merely is defined in the prescription that adopts in embodiment two, three, four.
In the above-described embodiments, what acid-base modifier adopted is citric acid or sodium citrate, 2N hydrochloric acid solution or sodium hydroxide, the acid-base modifier that the present invention relates to can also be acetic acid, phosphoric acid, potassium dihydrogen phosphate, sodium dihydrogen phosphate and ammonia, potassium hydroxide, and can select any one or a few the combination in above these acid-base modifiers.
In the above-described embodiments, what correctives adopted is sucralose, sucrose and steviosin, and the correctives that the present invention relates to can also be acesulfame potassium, and can select any one or a few the combination in above these correctivess, all can obtain effect preferably, the impurity level of generation is less.
In the above-described embodiments, what antiseptic adopted is methyl hydroxybenzoate, ethyl hydroxybenzoate and sodium benzoate, the antiseptic that the present invention relates to can also be benzoic acid, oxybenzene third fat, and can select any one or a few the combination in above these antiseptic, all can obtain effect preferably, the impurity level of generation is less.
In the above-described embodiments, what pigment adopted is lemon yellow, setting sun Huang and carmine, and the pigment that the present invention relates to can also be any one or a few the combination in above these pigments, all can obtain effect preferably, and the impurity level of generation is less.
In the above-described embodiments, what essence adopted is flavoring orange essence, Herba Menthae essence and black currant essence, the essence that the present invention relates to can also be tutti fruit essence, strawberry essence, flavoring banana essence, and can select any one or a few the combination in above these essence, all can obtain effect preferably, the impurity level of generation is less.
Claims (9)
1. a dextromethorphan hydrobromide guaifenesin oral liquid contains dextromethorphan hydrobromide, guaifenesin, acid-base modifier, purified water, it is characterized in that:
Wherein, described acid-base modifier is regulated the pH value of described dextromethorphan guaifenesin oral liquid in the 4.0-5.5 scope.
2. dextromethorphan hydrobromide guaifenesin oral liquid according to claim 1 is characterized in that:
Wherein, described acid-base modifier is regulated the pH value of described dextromethorphan hydrobromide guaifenesin oral liquid in the 4.4-4.8 scope.
3. dextromethorphan hydrobromide guaifenesin oral liquid according to claim 2 is characterized in that:
Wherein, to regulate the pH value of described dextromethorphan hydrobromide guaifenesin oral liquid be 4.8 to described acid-base modifier.
4. dextromethorphan hydrobromide guaifenesin oral liquid according to claim 1 is characterized in that:
Also contain correctives, antiseptic, pigment, essence.
5. dextromethorphan hydrobromide guaifenesin oral liquid according to claim 1 is characterized in that:
Wherein, described acid-base modifier is any one or a few the combination in hydrochloric acid solution, acetum, phosphoric acid solution, potassium dihydrogen phosphate, sodium dihydrogen phosphate, citric acid solution, sodium citrate solution, ammonia spirit, sodium hydroxide solution, the potassium hydroxide solution.
6. dextromethorphan hydrobromide guaifenesin oral liquid according to claim 1 is characterized in that:
Wherein, described acid-base modifier is citric acid solution or sodium citrate solution.
7. the described dextromethorphan hydrobromide guaifenesin of claim 4 oral liquid is characterized in that:
Wherein, described correctives is any one or a few the combination in sucrose, steviosin, sucralose, the acesulfame potassium,
Described antiseptic is any one or a few the combination in benzoic acid, sodium benzoate, methyl hydroxybenzoate, ethyl hydroxybenzoate, oxybenzene third fat,
Described pigment is any one or a few the combination in carmine, lemon yellow, the sunset yellow,
Described essence is any one or a few the combination in black currant essence, Herba Menthae essence, flavoring orange essence, tutti fruit essence, strawberry essence, the flavoring banana essence.
8. dextromethorphan hydrobromide guaifenesin oral liquid according to claim 7 is characterized in that:
Wherein, the concentration of described dextromethorphan hydrobromide is 1.5g/L, the concentration of described guaifenesin is 10g/L, described concentration of sucrose is 450g/L, the concentration of described sodium benzoate is 1g/L, the concentration of described methyl hydroxybenzoate is 1.5g/L, the concentration of described black currant essence is 2g/L, the concentration of described carmine is 6mg/L, the pH value of described dextromethorphan hydrobromide guaifenesin oral liquid is in the 4.6-4.8 scope, and described acid-base modifier is that concentration is the citric acid solution of 1-2mol/L, in the sodium citrate solution any one.
9. a method for preparing dextromethorphan hydrobromide guaifenesin oral liquid is characterized in that, may further comprise the steps:
A certain amount of correctives is dissolved in the purified water, after stirring and dissolving, then adds a certain amount of active carbon, and stir 10min, by removing by filter described active carbon, obtain solution one again;
A certain amount of dextromethorphan hydrobromide, guaifenesin, antiseptic, essence and pigment are added stirring and dissolving in the described solution one, obtain solution two;
Adopt acid-base modifier that the pH value of described solution two is adjusted in the 4.6-4.8 scope, obtain solution three;
The described purified water of certain volume is added described solution three, obtain solution four;
Described solution four is filtered, pass through flowing steam sterilization again, then fill obtains described dextromethorphan hydrobromide guaifenesin oral liquid,
Wherein, described correctives is sucrose, and described antiseptic is sodium benzoate, methyl hydroxybenzoate, and described essence is black currant essence, and described pigment is carmine,
The mass ratio of described dextromethorphan hydrobromide and described guaifenesin is 1.5:10,
The mass ratio of described dextromethorphan hydrobromide, described sucrose, described active carbon, described sodium benzoate, described methyl hydroxybenzoate, described black currant essence, described carmine is 1.5:450:1:1:1.5:2:0.006,
In described solution four, the concentration of described dextromethorphan hydrobromide is 1.5g/L.
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| CN104122361A (en) * | 2014-08-04 | 2014-10-29 | 人福普克药业（武汉）有限公司 | Method for analyzing daytime severe cold and flu capsules by high performance liquid chromatography |
| CN104224765B (en) * | 2014-09-03 | 2016-08-24 | 河北仁合益康药业有限公司 | A kind of more phenol bromine new oral administration solution compositions |
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| CN101904850A (en) * | 2010-08-17 | 2010-12-08 | 程雪翔 | Medicament for relieving cough and removing sputum and preparation method for syrup thereof |
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| CN101904850A (en) * | 2010-08-17 | 2010-12-08 | 程雪翔 | Medicament for relieving cough and removing sputum and preparation method for syrup thereof |
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| CN104122361A (en) * | 2014-08-04 | 2014-10-29 | 人福普克药业（武汉）有限公司 | Method for analyzing daytime severe cold and flu capsules by high performance liquid chromatography |
| CN104224765B (en) * | 2014-09-03 | 2016-08-24 | 河北仁合益康药业有限公司 | A kind of more phenol bromine new oral administration solution compositions |
| CN108434097A (en) * | 2018-06-22 | 2018-08-24 | 南京济群医药科技股份有限公司 | A kind of hydrochloric triprolidine oral solution of stabilization and preparation method thereof |
| CN109172551A (en) * | 2018-10-15 | 2019-01-11 | 江苏悦兴药业有限公司 | Pseudo- numb oral solution of Sugarless type and preparation method thereof |
| CN110302149A (en) * | 2019-08-07 | 2019-10-08 | 北京博达绿洲医药科技研究有限公司 | A kind of suitable 4-11 years old children taking anti-cold medicine and preparation method thereof |
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