CN110327339A - A kind of compound Dextromethorphan oral administration solution and its preparation method and application - Google Patents
A kind of compound Dextromethorphan oral administration solution and its preparation method and application Download PDFInfo
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Abstract
A kind of compound Dextromethorphan oral solution formulation of the present invention and its preparation method and application, it is to be equipped with the auxiliary materials such as the corrigent that a certain amount of stabilizer, cosolvent, thickener, suspending agent, emulsifier, PH regulator, preservative and suitable children receive using paracetamol, guaiacol glycerol ether, PHENYLEPHRINE HYDROCHLORIDE and dextromethorphan hydrobromide as active medicine and be processed into through scientific method.The present invention is suitable for 6-12 years old children taking, the present invention can treat and alleviate the symptom of common flu and influenza, such as nasal obstruction, cough and since slight throat and bronchial inflammation cough cause the intensity got excited, mild pain, headache, sore throat can be treated and be alleviated, fever is temporarily reduced.
Description
Technical field
The invention belongs to chemical drug research and development technology fields, and in particular to a kind of compound Dextromethorphan oral administration solution and preparation method thereof
And purposes.
Background technique
Respiratory disease is mostly caused by virus or germ, symptom such as nasal obstruction, runny nose, cough, sneezing, fever or headache
Deng being such as not treated in time, many complication, such as pneumonia, myocarditis can be caused, bring serious harm to people's body.
Commonly used in treat above-mentioned symptom drug mostly by antithistamine, antitussive, expectorant, arcotic, antipyretic,
And anti-inflammatory agent.Its dosage form is embodied in the dosage forms such as syrup, tablet, capsule, oral solution, effervescent tablet more.
Product such as neo-synephrine, guaiacol glycerol ether, chlorphenamine, the right U.S. for alleviating above-mentioned a variety of symptoms are husky
Fragrant, paracetamol isoreactivity ingredient, but be single use said medicine all there is unstability, and drug effect is single, it is right
Its drug combination is such as prepared into liquid oral or solid pharmaceutical preparation, is also easy to produce discoloration or has crystal to be precipitated and be also easy to produce effective component
Degradation etc., have been reported that, neo-synephrine is degradable under conditions of having aldehyde, metal and acid.
In addition, seldom in Chinese children cold drug, many parents mostly halve adult cold's medicine to take to child, in this way
Children's health can be impaired.In China because inappropriate medication either taking dose is excessive, lead to there are about 30,000 children to fall into nothing every year
The sound world causes hepatic and renal function, nervous system equivalent damage, is even more difficult to count.Again because not timing is taken medicine, drug is not achieved
One stable blood concentration causes to make drug play therapeutic effect well.Medication not timing, dosage is excessive, advises
Uneven lattice are the existing extremely serious problems of China's cold drug.On 2 26th, 2013, State Food and Drug Administration's hair
Cloth " opinion further encouraged innovations about in-depth drug evaluation examination & approval reform ", " encouraging to develop children " arranges as one
It applies and is individually listed.Emphasis encourages have the original new drug of clinical value and clinic need imitation medicine.
The applicant is directed to defect existing for cold drug described above according to the relevant policies that country puts into effect, it is necessary to
Study a kind of stable effective ingredients can children taking cold drug.
Summary of the invention
The present invention be directed to China to show children's cold drug less varieties, dosage form is few, dosage is excessive, specification is not complete and because of it
The defects of taste difficulty is taken and a kind of new drug developed, a kind of compound Dextromethorphan oral administration solution of the present invention, can treat and alleviate
The symptom of common flu and influenza such as nasal obstruction is coughed and since slight throat and bronchial inflammation cough cause the strong of impulsion
Degree, to help your child to fall asleep, can treat and alleviate mild pain, headache, sore throat, and temporarily reducing fever helps to loosen
The discharge of phlegm (mucus) and bronchiole secretion.
The present invention is by paracetamol, dextromethorphan hydrobromide, guaiacol glycerol ether, PHENYLEPHRINE HYDROCHLORIDE
The flavoring received for active constituent and a certain amount of stabilizer, cosolvent, thickener, PH regulator, preservative and suitable children
A kind of oral liquid that the auxiliary material combinations such as agent are process.
Paracetamol is the interior metabolism product of phenacetin, by inhibiting hypothalamus heat-regulating centers prostate
Plain synzyme.Reduce the synthesis and release of Prostaglandin PGE1, bradykinin and histamine etc..It is mainly adjusted by nerve in the present invention
Section causes peripheral blood vessel expansion, perspires and have the function that antipyretic.
It avoids applying simultaneously
Dextromethorphan hydrobromide is the dextroisomer of m orphine levo-dromoran methyl ether, by inhibiting oblongata coughing centre
Play central antitussive effect.Its antibechic intensity and codeine are quite or slightly strong.Without analgesic activity, prolonged application has no tolerance
With it is additive.Therapeutic dose does not inhibit to breathe.Oral absorption is good, works within 15~30 minutes, effect can maintain 3~6 hours.Blood plasma
Middle original shape drug concentration is very low, and for major active metabolite product 3- Codeine Aminoxyde alkane in Plasma height, t1/2 is 5 hours.
It is mainly used for alleviating and treating cough when dry cough and other infection of the upper respiratory tracts in the present invention.
Guaiacol glycerol ether is stimulant expectorant, can stimulate stomach lining, causes the secret increasing of respiratory tract body of gland point reflectingly
Add, dilute sputum, is easy to expectoration, is mainly used for phlegm-dispelling functions in the present invention.
PHENYLEPHRINE HYDROCHLORIDE is alpha adrenergic receptor excitomotor.This product is the sympathomimetic amine for directly acting on receptor
Class medicine, but also come into force sometimes indirectly by promoting norepinephrine to discharge from storage position.Act on α receptor (especially skin
Skin, mucous membrane, internal organ etc.), cause vessel retraction, peripheral resistance increases, and increases systolic pressure and diastolic pressure.In the present invention
Main function is expansion vascular smooth muscle and spasmolysis.
Realize that technical scheme is as follows:
Prescription: contain in 1000ml of the present invention:
1, active constituent: paracetamol 28.00-35.00g, guaiacol glycerol ether 15-25g, hydrochloric acid deoxygenate on kidney
Parathyrine 0.40-0.60g, dextromethorphan hydrobromide 0.80-1.20g,
2, other helper components: stable, non-degradable to reach active constituent in the present invention, children taking has compliance
Formulation requirements, the present invention is also added into 1.50-2.50g stabilizer, 400.00-600.00g cosolvent, 95.00-110.00g
Corrigent, 0.80-1.00g thickener, 2.50-3.20gPH regulator, 0.4-0.6g complexing agent, 1.90-2.10g preservative and
The pigment of 30.00-35.00mg and the aromatic of 3.00-5.00ml, solubilizer to 1000ml.
The stabilizer includes but is not limited to propylgallate, sodium thiosulfate, thiocarbamide, thioacetic acid, gallic acid
Propyl ester, hydroquinone, tea polyphenols, tocopherol, flavonoids, butylated hydroxy anisole, dibutyl hydroxy toluene, tert-butyl are to benzene two
Phenol and their mixture.It is further preferred that the stabilizer is propylgallate.
The cosolvent includes but is not limited to propylene glycol, glycerol, ethyl alcohol, it is further preferred that the cosolvent is glycerol
And propylene glycol mixture.
The corrigent includes but is not limited to sorbierite, sucrose, saccharin sodium, Steviosin, Sucralose, glycyrrhizic acid, into one
Preferably, the corrigent is the mixture of sorbierite and Sucralose to step.
The thickener include but is not limited to xanthan gum, carbomer, crosslinking sodium polyacrylate, poloxamer, polyvinyl alcohol,
Sodium alginate, further preferably xanthan gum.
The PH mediator agent includes but is not limited to potassium hydrogen phosphate, dibastic sodium phosphate, anhydrous citric acid, potassium dihydrogen phosphate or phosphoric acid
Sodium dihydrogen, it is further preferred that the PH mediator agent is the mixture of anhydrous citric acid and sodium citrate.
The preservative includes but is not limited to benzoic acid, sodium benzoate, sorbic acid, sodium sorbate, it is further preferred that institute
Stating preservative is sodium benzoate.
The complexing agent includes but is not limited to disodium ethylene diamine tetraacetate, natrium adetate, citric acid, phosphoric acid, further
Preferably, the complexing agent is natrium adetate.
The aromatic includes but is not limited to red grape essence, blueberry flavor, flavoring apple essence, orange essence, further excellent
Selection of land, the red grape essence of the aromatic and blueberry flavor mixture.
The pigment includes but is not limited to allured red pigment, brilliant blue pigment, brilliant green pigment, Yellow pigment, further preferably
Ground, the pigment are the mixture of allured red pigment and brilliant blue pigment.
The solvent includes but is not limited to purified water, deionized water or distilled water, it is preferable that the solvent is purified water.
Preparing method of the invention is, for preparing 1000ml:
1, precision weighs above-mentioned recipe quantity paracetamol, guaiacol glycerol ether is set in 500ml volumetric flask, successively plus
Enter corrigent, thickener, PH regulator, preservative, complexing agent and corrigent, shaking makes solid be uniformly dispersed and then be added prescription
Cosolvent is measured, shaking makes solid be uniformly dispersed or dissolve, and addition temperature is (70-90) DEG C solvent about 130-170ml, shakes up, object
After material dissolution, precision weighs recipe quantity PHENYLEPHRINE HYDROCHLORIDE, dextromethorphan hydrobromide and stabilizer, shakes up, at addition
Side amount pigment, aromatic, stand overnight, solubilizer makes medical fluid reach 1000ml, shake up, filter, it is filling to get.
Preparation method can also be (for preparation 1000ml):
1, the cosolvent for weighing recipe quantity is set in 1000mL beaker, be placed under 55-65 DEG C of water bath condition heat after, successively plus
Enter recipe quantity thickener, shake up, paracetamol, the guaiacol glycerol ether that precision weighs recipe quantity uniformly keep its molten
Solution, obtains material a；
2, recipe quantity corrigent, complexing agent, PH regulator, preservative are weighed to set in 500mL beaker, solvent 300- is added
400ml is heated to 70-90 DEG C or so, stirs to solution clear, obtains material b；
3, material b is transferred in material a, material b container is rinsed 2-3 times, flushing liquor is transferred to material a container
In, continue to stir, obtains material c；
4, under stirring, PHENYLEPHRINE HYDROCHLORIDE, the dextromethorphan hydrobromide, stabilization of recipe quantity are added in material c
Agent, pigment, aromatic supplement remaining recipe quantity solvent to 1000ml, and filtering is cooled to room temperature, filling, to obtain the final product.
Preparation method of the invention is preferably (for preparation 1000ml):
1, weigh glycerol 200g, propylene glycol 300g is set in 1000mL beaker, be placed under 60 DEG C of water bath conditions, sequentially add place
Side amount xanthan gum 0.95g, paracetamol 32.50g, guaiacol glycerol ether 20.00g, stir evenly, obtain material a；
2, sorbierite 100g, natrium adetate 0.50g, sodium citrate 1.00g, anhydrous citric acid 1.90g, trichlorine sugarcane are weighed
Sugared 2.50g, sodium benzoate 2.00g are set in 500mL beaker, and ready 80 DEG C of purified water 350ml are added, and stirring to solution is clarified
It is transparent, obtain material b；
3, material b being transferred in material a, material b container is rinsed 2 times, flushing liquor is transferred in material a container,
Continue to stir, obtains material c；
4, PHENYLEPHRINE HYDROCHLORIDE 0.50g is added under stirring, in material c, dextromethorphan hydrobromide 1.00g, does not have
Propyl galate 2.00g, brilliant blue pigment 28.5mg, allured red pigment 5.00mg, blueberry flavor 2.5ml and red grape essence
1.50ml adds purified water to stir evenly to 1000ml, filters, it is filling to get.
A kind of compound Dextromethorphan oral administration solution of the present invention, can treat and alleviate the symptom of common flu and influenza: nose
Plug is coughed and since slight throat and bronchial inflammation cough cause the intensity of impulsion that can treat to help your child to fall asleep
With alleviation mild pain, headache, sore throat, temporarily reducing fever helps to loosen the row of phlegm (mucus) and bronchiole secretion
Out.
The present invention is suitable for 6-12 years old children taking, each taking 10 milliliters, takes within every 4 hours primary.
Beneficial effect
A kind of compound Dextromethorphan oral solution formulation of the present invention and its preparation method and application, is with acetparaminosalol
Phenol, guaiacol glycerol ether, PHENYLEPHRINE HYDROCHLORIDE and dextromethorphan hydrobromide are active medicine, are equipped with a certain amount of stabilization
The auxiliary materials groups such as the corrigent that agent, cosolvent, thickener, suspending agent, emulsifier, PH regulator, preservative and suitable children receive
At.The present invention is suitable for 6-12 years old children taking, can treat and alleviate the symptom of common flu and influenza: nasal obstruction, cough and
Since slight throat and bronchial inflammation cough cause the intensity of impulsion, to help your child to fall asleep, it can treat and alleviate light
Micro- pain, headache, sore throat, temporarily reducing fever helps to loosen the discharge of phlegm (mucus) and bronchiole secretion.
Specific embodiment:
Now with regard to several specific embodiments, next the present invention is further explained
Embodiment 1
Prescription:
1, active constituent: paracetamol 34.00g, guaiacol glycerol ether 21.50g, PHENYLEPHRINE HYDROCHLORIDE
0.47g, dextromethorphan hydrobromide 0.95g
2, other helper components: propylgallate 1.75g, propylene glycol 300.00g, glycerol 100.00g, sorbierite
95.00g, xanthan gum 1.00g, potassium hydrogen phosphate 1.70g, potassium dihydrogen phosphate 1.00g, natrium adetate 0.40g, sucrose 100.00g,
Sorbic acid 1.95g and allured red pigment 34.00mg and flavoring apple essence 3.00ml, adds purified water to 1000ml.
Preparation method:
1, precision weighs above-mentioned recipe quantity paracetamol 34.0g, guaiacol glycerol ether 21.5g sets 500ml capacity
Bottle in, sequentially add 95.0g, xanthan gum 1.00g, potassium hydrogen phosphate 1.70g, potassium dihydrogen phosphate 1.00, sorbic acid 1.95g, according to ground
Acid disodium 0.40g, shaking make solid be uniformly dispersed, and recipe quantity propylene glycol 300.00g, glycerol 100.00g is then added, and shaking makes
Solid dissolution, addition temperature are (70-90) DEG C solvent about 130-170ml, are shaken up, after material dissolution, precision weighs recipe quantity salt
Sour neo-synephrine 0.47g, dextromethorphan hydrobromide 0.95g and propylgallate 1.75g, shake up, and recipe quantity is added
Allured red pigment 34.00mg, flavoring apple essence 3.00ml, stand overnight, add purified water, medical fluid is made to reach 1000ml, shake up, mistake
Filter, it is filling to get.
Embodiment 2
Prescription: 1, active constituent: paracetamol 28.00g, guaiacol glycerol ether 20.00g, hydrochloric acid deoxygenate on kidney
Parathyrine 0.60g, dextromethorphan hydrobromide 1.00g,
2, other helper components: 1.60g tert-butyl hydroquinone, 300.00g propylene glycol, 150.00g glycerol, 100.00g
Sucrose, 0.90g poloxamer, 1.80g anhydrous citric acid and 0.90g sodium citrate, 0.60g phosphoric acid, 2.10g sodium benzoate and
35.00mg brilliant blue pigment and the red grape essence of 3.50ml, add deionized water to 1000ml.
Preparation method: 1, weighing the propylene glycol of recipe quantity, glycerol is set in 1000mL beaker, be placed under 60 DEG C of water bath conditions plus
After heat, recipe quantity poloxamer being sequentially added, is shaken up, precision weighs paracetamol, the guaiacol glycerol ether of recipe quantity,
Uniformly, it makes it dissolve, obtains material a；
2, recipe quantity sucrose, phosphoric acid, anhydrous citric acid, sodium citrate, sodium benzoate are weighed to set in 500mL beaker, is added
Purified water 300-400ml is heated to 70-90 DEG C or so, stirs to solution clear, obtains material b；
3, material b is transferred in material a, material b container is rinsed 2-3 times, flushing liquor is transferred to material a container
In, continue to stir, obtains material c；
4, under stirring, PHENYLEPHRINE HYDROCHLORIDE, the dextromethorphan hydrobromide, tertiary fourth of recipe quantity are added in material c
Base hydroquinone, brilliant blue pigment, red grape essence supplement remaining recipe quantity purified water to 1000ml, and filtering is cooled to room temperature,
It is filling, to obtain the final product.
Embodiment 3
1, active constituent: paracetamol 32.5g, guaiacol glycerol ether 20.00g, PHENYLEPHRINE HYDROCHLORIDE
0.60g, dextromethorphan hydrobromide 1.00g,
2, other helper components: natrium adetate, 0.5g glycerol 200g, propylene glycol, 300.00g xanthan gum 0.95g, anhydrous
Citric acid and 1.90g sodium citrate 1.00g, sorbierite 100.0g, Sucralose 2.5g, sodium benzoate 2.00g, gallic acid third
Ester 2.00g, brilliant blue pigment 28.5mg, the red grape essence of allured red pigment 5.0mg and 1.5ml, add deionized water to 1000ml.
Preparation method:
Weigh glycerol 200g, propylene glycol 300g is set in 1000mL beaker, be placed under 60 DEG C of water bath conditions, sequentially add prescription
Xanthan gum 0.95g, paracetamol 32.50g, guaiacol glycerol ether 20.00g are measured, stirs evenly, obtains material a；
12.2, sorbierite 100g, natrium adetate 0.5g, sodium citrate 1.00g, anhydrous citric acid 1.90g, trichlorine are weighed
Sucrose 2.50g, sodium benzoate 2.00g are set in 500mL beaker, and ready 80 DEG C of purified water 350ml are added, and are stirred clear to solution
It is clear bright, obtain material b；
12.3, material b is transferred in material a, material b container is rinsed 2 times, flushing liquor is transferred to material a container
In, continue to stir, obtains material c；
12.4, under stirring, in material c be added PHENYLEPHRINE HYDROCHLORIDE 0.50g, dextromethorphan hydrobromide 1.00g,
Propylgallate 2.00g, brilliant blue pigment 28.5mg, allured red pigment 5.00mg, blueberry flavor 2.5ml and red grape essence
1.50ml adds purified water to stir evenly to 1000ml, filters, it is filling to get.
1, active constituent: paracetamol 32.50g, guaiacol glycerol ether 20.00g, PHENYLEPHRINE HYDROCHLORIDE
0.50g, dextromethorphan hydrobromide 1.00g
2, other auxiliary elements: glycerol 200g, propylene glycol 300g, xanthan gum 0.95g, sorbierite 100g, natrium adetate
0.50g, sodium citrate 1.00g, anhydrous citric acid 1.90g, Sucralose 2.50g, sodium benzoate 2.00g, propylgallate
2.00g, brilliant blue pigment 28.5mg, allured red pigment 5.00mg, blueberry flavor 2.5ml and red grape essence 1.50ml,
Preparation method:
1, weigh glycerol 200g, propylene glycol 300g is set in 1000mL beaker, be placed under 60 DEG C of water bath conditions, sequentially add place
Side amount xanthan gum 0.95g, paracetamol 32.50g, guaiacol glycerol ether 20.00g, stir evenly, obtain material a；
2, sorbierite 100g, natrium adetate 0.50g, sodium citrate 1.00g, anhydrous citric acid 1.90g, trichlorine sugarcane are weighed
Sugared 2.50g, sodium benzoate 2.00g are set in 500mL beaker, and ready 80 DEG C of purified water 350ml are added, and stirring to solution is clarified
It is transparent, obtain material b；
3, material b being transferred in material a, material b container is rinsed 2 times, flushing liquor is transferred in material a container,
Continue to stir, obtains material c；
4, PHENYLEPHRINE HYDROCHLORIDE 0.50g is added under stirring, in material c, dextromethorphan hydrobromide 1.00g, does not have
Propyl galate 2.00g, brilliant blue pigment 28.5mg, allured red pigment 5.00mg, blueberry flavor 2.5ml and red grape essence
1.50ml adds purified water to stir evenly to 1000ml, filters, it is filling to get.
Embodiment 4
Prescription:
1, active constituent: paracetamol 29.00g, guaiacol glycerol ether 22.00g, PHENYLEPHRINE HYDROCHLORIDE
0.50g, dextromethorphan hydrobromide 1.10g
2, other helper components: 2.20g sodium thiosulfate, 400.00g propylene glycol, 150.00g glycerol, 110.00 sucrose,
1.50g Steviosin, 0.95g xanthan gum, 1.80g potassium dihydrogen phosphate, 0.90g sodium dihydrogen phosphate, 0.40g ethylenediamine tetra-acetic acid two
The brilliant blue pigment of sodium, 2.08g sodium benzoate and 30.00mg and the orange essence of 4.00ml, add purified water to 1000ml.
Preparation method:
1, weigh the propylene glycol of recipe quantity, glycerol is set in 1000mL beaker, be placed under 55-65 DEG C of water bath condition heat after,
Recipe quantity xanthan gum is sequentially added, is shaken up, paracetamol, the guaiacol glycerol ether that precision weighs recipe quantity uniformly make
It is dissolved, and obtains material a；
2, recipe quantity sucrose, Steviosin, disodium ethylene diamine tetraacetate, potassium dihydrogen phosphate, sodium dihydrogen phosphate, benzoic acid are weighed
Sodium is set in 500mL beaker, and solvent 300-400ml is added, and is heated to 70-90 DEG C or so, is stirred to solution clear, is obtained material
b；
3, material b is transferred in material a, material b container is rinsed 2-3 times, flushing liquor is transferred to material a container
In, continue to stir, obtains material c；
4, the PHENYLEPHRINE HYDROCHLORIDE of recipe quantity, dextromethorphan hydrobromide, thio is added under stirring, in material c
Sodium sulphate, brilliant blue pigment, orange essence supplement remaining recipe quantity purified water to 1000ml, and filtering is cooled to room temperature, filling, i.e.
?.
Embodiment 5
Stability test 1- high temperature, high humidity and exposure experiments to light
1, sample source: Beijing boda oasis medical sci-tech is studied Co., Ltd and is provided.
2, instrument and equipment: Shimadzu LC16 liquid phase chromatograph system；CP124S electronic analytical balance (SARTORIUS, moral
State)；BP211D electronic analytical balance (SARTORIUS, Germany)；(it is limited that Beijing North grinds tech instrument to ZRD-1402PA digestion instrument
Responsible company)；LHH-150SOP stability test case (Shanghai Yiheng Scientific Instruments Co., Ltd)；Chromatographic column: ACE column
(Excer5 Super C18 250×4.6mm id 5μm)
3, test method: 30 liters of sample made from Example 3, every filling 100ml are divided in white glass bottle,
Sealing, is divided into 3 groups, and 100 are one group, respectively high temperature (60 DEG C), high humidity (92% ± 5%) and illumination (illumination 4500Lx ±
It is placed 30 days under the conditions of 500Lx), with paracetamol (being indicated with A), guaiacol glycerol ether (being indicated with B), hydrochloric acid deoxidation
Adrenaline (being indicated with C) and dextromethorphan hydrobromide (indicate) that content is Testing index with D, sample at the 10th day and the 30th day
Detection.It the results are shown in Table 1.
Sample detection situation table under 1 high temperature of table, high humidity and illumination condition
Experiments have shown that: the said goods are under high temperature, Qiang Guang, super-humid conditions, and indexs can occur one again etc. for effective component and ball
Fixed variation, prompts the product preservation condition that should be protected from light, low temperature, keeps drying.Embodiment six
Stability test 2: primary stability test
1, sample source: Beijing boda oasis medical sci-tech is studied Co., Ltd and is provided.
2, instrument and equipment: Shimadzu LC16 liquid phase chromatograph system；CP124S electronic analytical balance (SARTORIUS, moral
State)；BP211D electronic analytical balance (SARTORIUS, Germany)；(it is limited that Beijing North grinds tech instrument to ZRD-1402PA digestion instrument
Responsible company)；LHH-150SOP stability test case (Shanghai Yiheng Scientific Instruments Co., Ltd)；Chromatographic column: ACE column
(Excer5 Super C18 250×4.6mm id 5μm)
3, test method: 10 liters of sample made from Example 3, every filling 100ml are divided in white glass bottle,
Sealing is placed in 40 DEG C ± 2 DEG C, in the environment of relative humidity 92% ± 5%, more plain by ammonia U.S.A respectively at 0,1,2,3, sampling in June
Gainer under the quality standard draft item of oral solution is investigated, and the results are shown in Table 2.
Table 2: primary stability test
Experiments have shown that: through primary stability experiment investigation, quality meets bound requirements, and content illustrates matter without significant change
Amount is stablized.Illustrate:
1, bound requirements, --- -- " drug impurity analysis guideline " (2005 editions) by the national drug standards
2, in table 2, more wound A is indicated: guaiacol glycerol ether impurity A；More wound B is indicated: guaiacol glycerol ether impurity B；
More wound C is indicated: guaiacol glycerol ether impurity C；More wound D is indicated: guaiacol glycerol ether impurity D；Deoxygenating A indicates: hydrochloric acid is gone
Upper adrenaline impurity A；Deoxygenating C indicates: hydrochloric acid removes adrenaline impurity C；Deoxygenating D indicates: hydrochloric acid goes adrenaline miscellaneous
Matter D；Deoxygenating E indicates: hydrochloric acid removes adrenaline impurity E；Right beauty A is indicated: dextromethorphan hydrobromide impurity A；Right beauty B is indicated:
Dextromethorphan hydrobromide impurity B；Right beauty C: dextromethorphan hydrobromide impurity C；Right U.S. nitrogen oxides indicates: dextromethorphan hydrobromide
Impurity IV.
Claims (16)
1. a kind of compound Dextromethorphan oral administration solution and its preparation method and application, it is characterised in that contain in 1000ml of the present invention:
Active constituent: paracetamol 28.00-35.00g, guaiacol glycerol ether 15-25g, PHENYLEPHRINE HYDROCHLORIDE 0.40-
0.60g, dextromethorphan hydrobromide 0.80-1.20g, other helper components: 1.50-2.50g stabilizer, 400.00-600.00g are helped
Solvent, 95.00-110.00g corrigent, 0.80-1.00g thickener, 2.50-3.20PH regulator, 0.4-0.6g complexing agent,
The aromatic of the pigment and 3.00-5.00ml of 1.90-2.10g preservative and 30.00-35.00mg, solubilizer to 1000ml.
2. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
The stabilizer include but is not limited to propylgallate, sodium thiosulfate, thiocarbamide, thioacetic acid, propylgallate, to benzene
Diphenol, tea polyphenols, tocopherol, flavonoids, butylated hydroxy anisole, dibutyl hydroxy toluene, tert-butyl hydroquinone and he
Mixture.It is further preferred that the stabilizer is propylgallate.
3. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
The cosolvent includes but is not limited to propylene glycol, glycerol, ethyl alcohol, it is further preferred that the cosolvent is glycerol and propylene glycol
Mixture.
4. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
The corrigent includes but is not limited to sorbierite, sucrose, saccharin sodium, Steviosin, Sucralose, glycyrrhizic acid, it is further preferred that
The corrigent is the mixture of sorbierite and Sucralose.
5. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
The thickener includes but is not limited to xanthan gum, carbomer, crosslinking sodium polyacrylate, poloxamer, polyvinyl alcohol, alginic acid
Sodium, further preferably xanthan gum.
6. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
The PH mediator agent includes but is not limited to potassium hydrogen phosphate, dibastic sodium phosphate, anhydrous citric acid, potassium dihydrogen phosphate or sodium dihydrogen phosphate,
It is further preferred that the PH mediator agent is the mixture of anhydrous citric acid and sodium citrate.
7. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
The preservative includes but is not limited to benzoic acid, sodium benzoate, sorbic acid, sodium sorbate, it is further preferred that the preservative
For sodium benzoate.
8. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
The complexing agent includes but is not limited to disodium ethylene diamine tetraacetate, natrium adetate, citric acid, phosphoric acid, it is further preferred that institute
Stating complexing agent is natrium adetate.
9. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
The aromatic includes but is not limited to red grape essence, blueberry flavor, flavoring apple essence, orange essence, it is further preferred that described
The red grape essence of aromatic and blueberry flavor mixture.
10. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
The pigment includes but is not limited to allured red pigment, brilliant blue pigment, brilliant green pigment, Yellow pigment, it is further preferred that the color
Element is the mixture of allured red pigment and brilliant blue pigment.
11. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
The solvent includes but is not limited to purified water, deionized water or distilled water, it is preferable that the solvent is purified water.
12. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
Preparing method of the invention is, for preparing 1000ml: it is sweet that precision weighs above-mentioned recipe quantity paracetamol, guaiacol
Oily ether is set in 500ml volumetric flask, and corrigent, thickener, PH regulator, preservative, complexing agent and corrigent are sequentially added, shaking
So that solid is uniformly dispersed and recipe quantity cosolvent is then added, shaking makes solid be uniformly dispersed or dissolve, and it is (70-90) that temperature, which is added,
DEG C solvent about 130-170ml, shakes up, and after material dissolution, it is husky that precision weighs the right U.S. of recipe quantity PHENYLEPHRINE HYDROCHLORIDE, hydrobromic acid
Fragrant and stabilizer, shakes up, and recipe quantity pigment, aromatic is added, stands overnight, solubilizer makes medical fluid reach 1000ml, shakes
It is even, filtering, it is filling to get.
13. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
Preparation method is also possible that for preparation 1000ml:
13.1, the cosolvent for weighing recipe quantity is set in 1000mL beaker, be placed under 55-65 DEG C of water bath condition heat after, successively plus
Enter recipe quantity thickener, shake up, paracetamol, the guaiacol glycerol ether that precision weighs recipe quantity uniformly keep its molten
Solution, obtains material a；
13.2, recipe quantity corrigent, complexing agent, PH regulator, preservative are weighed to set in 500mL beaker, solvent 300- is added
400ml is heated to 70-90 DEG C or so, stirs to solution clear, obtains material b；
13.3, material b being transferred in material a, material b container is rinsed 2-3 times, flushing liquor is transferred in material a container,
Continue to stir, obtains material c；
13.4, under stirring, PHENYLEPHRINE HYDROCHLORIDE, the dextromethorphan hydrobromide, stabilization of recipe quantity are added in material c
Agent, pigment, aromatic supplement remaining recipe quantity solvent to 1000ml, and filtering is cooled to room temperature, filling, to obtain the final product.
14. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
Preparation method preferably, prepare 1000ml for:
14.1, weigh glycerol 200g, propylene glycol 300g is set in 1000mL beaker, be placed under 60 DEG C of water bath conditions, sequentially add place
Side amount xanthan gum 0.95g, paracetamol 32.50g, guaiacol glycerol ether 20.00g, stir evenly, obtain material a；
14.2, sorbierite 100g, natrium adetate 0.50g, sodium citrate 1.00g, anhydrous citric acid 1.90g, Sucralose are weighed
2.50g, sodium benzoate 2.00g are set in 500mL beaker, and ready 80 DEG C of purified water 350ml are added, and stirring is saturating to solution clarification
It is bright, obtain material b；
14.3, material b being transferred in material a, material b container is rinsed 2 times, flushing liquor is transferred in material a container, after
Continuous stirring, obtains material c；
14.4, PHENYLEPHRINE HYDROCHLORIDE 0.50g is added under stirring, in material c, dextromethorphan hydrobromide 1.00g, does not eat
Sub- propyl propionate 2.00g, brilliant blue pigment 28.5mg, allured red pigment 5.00mg, blueberry flavor 2.5ml and red grape essence
1.50ml adds purified water to stir evenly to 1000ml, filters, it is filling to get.
15. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
A kind of compound Dextromethorphan oral administration solution of the present invention, can treat and alleviate the symptom of common flu and influenza: nasal obstruction, cough and
Since slight throat and bronchial inflammation cough cause the intensity of impulsion, to help your child to fall asleep, it can treat and alleviate light
Micro- pain, headache, sore throat, temporarily reducing fever helps to loosen the discharge of phlegm (mucus) and bronchiole secretion.
16. a kind of compound Dextromethorphan oral administration solution and its preparation method and application according to claim 1, it is characterised in that
The present invention is suitable for 6-12 years old children taking, each taking 10 milliliters, takes within every 4 hours primary.
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| CN111437250A (en) * | 2020-04-23 | 2020-07-24 | 合肥医工医药股份有限公司 | Stable mefenanamine ammonium oral solution and preparation method thereof |
| CN112076183A (en) * | 2020-08-28 | 2020-12-15 | 北京博达绿洲医药科技研究有限公司 | Liquid compositions comprising phenylephrine hydrochloride |
| CN112263580A (en) * | 2020-11-24 | 2021-01-26 | 四川逢春制药有限公司 | Compound oral solution and preparation method thereof |
| CN114159387A (en) * | 2021-12-10 | 2022-03-11 | 江苏汉晨药业有限公司 | Dextromethorphan hydrobromide oral solution |
| CN114533664A (en) * | 2022-01-29 | 2022-05-27 | 江苏广承药业有限公司 | Compound oral liquid preparation of dextromethorphan hydrobromide and guaiacol glyceryl ether |
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