CN101890049B - Pediatric paracetamol oral solution formula and preparation method thereof - Google Patents
Pediatric paracetamol oral solution formula and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a pediatric paracetamol oral solution formula and a preparation method thereof, and oral solution thereof is a compound preparation which mainly comprises acetaminophen, artificial bezoar, chlorpheniramine maleate and glacial acetic acid or citric acid. The key of the preparation method is to use the glacial acetic acid or the citric acid to dissolve the artificial bezoar, thereby improving the solubility of cholic acid which is a main active ingredient in the artificial bezoar from 77% by solid particles to above 95%, further greatly improving the human bioavailability of the cholic acid.
Description
Technical field
The present invention relates to a kind of is active component with 4 kinds of medicine supplementary materials of acetaminophen, artificial Calculus Bovis, chlorphenamine maleate and glacial acetic acid (perhaps citric acid), oral administration solution pharmaceutical preparation that is prepared from and preparation method thereof.Relate in particular to the method for preparing that is prepared into pediatric paracetamol oral solution with acetaminophen, artificial Calculus Bovis, chlorphenamine maleate and glacial acetic acid (or citric acid).
Background technology
As everyone knows, flu is human modal disease, thereby the medicine of treatment flu worldwide can be described as innumerablely, emerges in an endless stream.China is as a big country that 1,300,000,000 populations are arranged, and coldrex market is very huge, and the China of more holding concurrently has the traditional habit of using Chinese medicine, and the Chinese medicine of treatment flu and the kind analogy other countries of Western medicine and compound preparation are more.
It is synthetic that acetaminophen can suppress prostaglandin, has analgesic, analgesic activity, is used for the heating that children's's common cold or influenza cause, also is used to alleviate mild to moderate pain such as arthralgia, migraine, headache, myalgia, toothache, neuralgia.Chlorphenamine maleate is as the H of histamine
1Receptor antagonist can reduce the permeability of blood capillary to the telangiectasis due to the antianaphylaxis (histamine), alleviates bronchial smooth muscle panting due to shrinking, and its antihistamine effect is more lasting, also has tangible central inhibitory action.Chlorphenamine maleate is applicable to skin allergy mainly at liver metabolism: urticaria, eczema, dermatitis, drug eruption, skin pruritus, neurodermatitis, insect bite disease, solar dermatitis; Also can be used for allergic rhinitis, medicine and food anaphylaxis.The artificial Calculus Bovis has heat clearing away, detoxifcation, and relieving convulsion effect is usually used in treating diseases such as infantile hyperpyrexia, tic.The glacial acetic acid of low concentration (being glacial acetic acid) has the effect of bacteriostasis and sterilization; Effectiveness with respiratory tract pathogenic microorganism such as killing first streptococcus, card ground coccus, Diplococcus pneumoniae, Staphylococcus albus and influenza virus; Simultaneously can regulate gastrointestinal function, impel digestive juice secretion, thereby promote appetite.So glacial acetic acid is considered to the effect of prevention and treatment flu all the time.
The present invention just is being based on the pharmacological action of above-mentioned main supplementary material, on the basis with reference to the medicine pediatric paracetamol,atificial cowbezoar and chlorphenamine maleate granule prescription that goes on the market, innovates perfect new medicinal preparation.
Retrieve " a kind of pediatric paracetamol artifical low-bezoar and chlorphenzmine maleategel preparation and preparation method thereof " (patent No. ZL 200510060868.1) patent of invention; The characteristics of this patent are acetaminophen, artificial Calculus Bovis and 3 kinds of medicine materials of chlorphenamine maleate are processed gel; The inherent solid forms of its raw material does not change; As what narrate in its description, this invention " drug dissolution and bioavailability do not have obvious change than granule ".Here said granule promptly is a medicine " pediatric paracetamol,atificial cowbezoar and chlorphenamine maleate granule " in the market.
The pediatric paracetamol,atificial cowbezoar and chlorphenamine maleate granule agent is the specific drug of treatment children's common cold, also is the existing main preparation of Xiao ' er Anfen Huangnamin.But granule needs warm boiled water, and children's itself just produces huge resistance emotion for taking medicine during catching a cold, influence clinical application effect.And granule because the water yield that adds is different, often causes the totally different of taste when taking after mixing it with water.Gel is compared with granule, also has above-mentioned shortcoming.
Summary of the invention
The objective of the invention is to invent a kind of compound preparation and method for preparing of forming with acetaminophen, artificial Calculus Bovis, chlorphenamine maleate and glacial acetic acid (perhaps citric acid).Specifically, be exactly to be key component with acetaminophen, artificial Calculus Bovis, chlorphenamine maleate and glacial acetic acid (perhaps citric acid), be prepared into pediatric paracetamol oral solution.The indication of oral administration solution of the present invention is mainly used in the headache that causes of treatment infantile common cold, heating, throat pain, nasal obstruction etc.
The present invention also comprises cosolvent, stabilizing agent, antiseptic, coloring agent and correctives etc. except that key component is acetaminophen, artificial Calculus Bovis and chlorphenamine maleate and glacial acetic acid (perhaps citric acid).
The present invention is except that acetaminophen, artificial Calculus Bovis, chlorphenamine maleate and glacial acetic acid (perhaps citric acid) active component is prepared into the novel form oral solution; Comprise also and use cosolvent, stabilizing agent, antiseptic, coloring agent and correctives that the dissolving artificial Calculus Bovis also keeps the innovation production technology of artificial Calculus Bovis's active component.
The objective of the invention is to accomplish by following technical proposals:
Technical scheme one
A kind of pediatric paracetamol oral solution, it is characterized in that mainly by following material by weight, volume ratio forms:
0.5～12.5 part of acetaminophen
0.01～1 part of artificial Calculus Bovis
0.001～0.1 part of chlorphenamine maleate
0.05～60 part of glacial acetic acid
0～30 part of cosolvent
0～30 part of stabilizing agent
0～30 part of antiseptic
0～500 part of correctives
0～20 part of coloring agent
Be settled to 1000 parts (volumes) with purified water
Technical scheme two
A kind of pediatric paracetamol oral solution, it is characterized in that mainly by following material by weight, volume ratio forms:
0.5～12.5 part of acetaminophen
0.01～1 part of artificial Calculus Bovis
0.001～0.1 part of chlorphenamine maleate
0.05～50 part of citric acid
0～30 part of cosolvent
0～30 part of stabilizing agent
0～30 part of antiseptic
0～500 part of correctives
0～20 part of coloring agent
Be settled to 1000 parts (volumes) with purified water
Pediatric paracetamol oral solution of the present invention preferably fill a prescription 1 by following material by weight, volume ratio forms:
12.5 parts of acetaminophen
0.5 part of artificial Calculus Bovis
0.05 part of chlorphenamine maleate
7.34 parts of glacial acetic acids
3 parts of potassium sorbate
Be settled to 1000 parts (volumes) with purified water.
Pediatric paracetamol oral solution of the present invention preferably fill a prescription 2 by following material by weight, volume ratio forms:
12.5 parts of acetaminophen
0.5 part of artificial Calculus Bovis
0.05 part of chlorphenamine maleate
12 parts of citric acids
3 parts of potassium sorbate
Be settled to 1000 parts (volumes) with purified water.
Pediatric paracetamol oral solution of the present invention preferably fill a prescription 3 by following material by weight, volume ratio forms:
12.5 parts of acetaminophen
0.5 part of artificial Calculus Bovis
0.05 part of chlorphenamine maleate
7.34 parts of glacial acetic acids
5 parts of tween 80s
3 parts of sodium benzoate
Be settled to 1000 parts (volumes) with purified water.
Pediatric paracetamol oral solution of the present invention preferably fill a prescription 4 by following material by weight, volume ratio forms:
12.5 parts of acetaminophen
0.5 part of artificial Calculus Bovis
0.05 part of chlorphenamine maleate
7.34 parts of glacial acetic acids
5 parts of tween 80s
3 parts of potassium sorbate
50 parts of sucrose
Be settled to 1000 parts (volumes) with purified water.
Pediatric paracetamol oral solution of the present invention preferably fill a prescription 5 by following material by weight, volume ratio forms:
12.5 parts of acetaminophen
0.5 part of artificial Calculus Bovis
0.05 part of chlorphenamine maleate
7.34 parts of glacial acetic acids
3 parts of potassium sorbate
8 parts of Aspartane
0.5 part of strawberry essence
Be settled to 1000 parts (volumes) with purified water.
Among technical scheme one, technical scheme two and the 1-5 that preferably fills a prescription, the corresponding relation between the described weight and volume is defined as: the corresponding ml of g, the corresponding L of kg.
Cosolvent in the pediatric paracetamol oral solution production technology of the present invention includes but not limited to ethanol, ethylene glycol, 1, one or more in 2-propylene glycol, glycerin, tartaric acid, maleic acid, Aspartic Acid, fumaric acid, lactobionic acid, hydrochloric acid, sulphuric acid, the phosphoric acid.
Stabilizing agent comprises but is not limited to one or more of tween 80, tween-100, tween 20 0, Tween-40 0, Macrogol 600, polyethylene glycol 6000.
Antiseptic includes but not limited to one or more in methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, butoben, sodium benzoate, sorbic acid, the potassium sorbate.
Coloring agent includes but not limited to one or more in No. 6, FD& yellow, red No. 3 of FD&, red No. 33 of FD&, blue berry color pigment, brown pigmentation, the food coloring.
Correctives includes but not limited to one or more in sucrose, menthol, Aspartane, saccharin sodium, sucralose, cherry essence, strawberry essence, vanilla, fragrant citrus essence, Fructus Citri tangerinae essence and other essence.
The method for preparing of pediatric paracetamol oral solution of the present invention:
1. use the glacial acetic acid of prescription inventory, the artificial Calculus Bovis of inventory is dissolved fully (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving), stir 0.5～12h; Leave standstill; With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2. in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen of inventory, be stirred to abundant dissolving.
3. in the material-compound tank that dissolves acetaminophen fully, add the chlorphenamine maleate of inventory, stir, be cooled to room temperature.
4. the settled solution that obtains in material-compound tank, adding 1.; Fully stir; Add cosolvent, stabilizing agent, antiseptic, correctives and coloring agent after stirring successively, to be stirred well to the solution mix homogeneously behind the purified water standardize solution, with 0.45 and 0.22 micron filter membrane cascade filtration.
5. get intermediate check pH value, pH value is 2.0～6.5 to be qualified (regulating with hydrochloric acid or sodium hydroxide).
6. after the assay was approved, fill is that 5ml/ props up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution finished product of 100ml/ bottle or 120ml/ bottle.
PH value in the technology is meant the intermediate optimum that feeds intake definite according to difference, is 2.0～6.5.
The present invention has changed acetaminophen, artificial Calculus Bovis and 3 kinds of medicine materials of chlorphenamine maleate the form that exists of existing preparation; Be dissolved in the medium and exist with the state of free molecule; Especially in this dissolved state; The artificial Calculus Bovis has guaranteed that its main active component cholic acid is evenly distributed in the dissolve medium, has fundamentally solved artificial Calculus Bovis's problems of dissolution after being to use glacial acetic acid (perhaps citric acid) with the special process dissolving.So than granule and gel, change has taken place the state that all raw materials exist among the present invention, according to medicine knowledge general knowledge, oral administration solution novel form of the present invention has improved the bioavailability of medicine, has reduced the side effect of other dosage forms.
Characteristics of the present invention are:
1, the dosage form of innovation.
Acetaminophen, artificial Calculus Bovis, chlorphenamine maleate and glacial acetic acid (perhaps citric acid) are used fully dissolving such as cosolvent, stabilizing agent, be prepared into the oral administration solution novel form.
2, the production technology of innovation
Use cosolvent, stabilizing agent that the artificial Calculus Bovis is fully dissolved, kept the active component that has the curative effect of medication effect among the artificial Calculus Bovis, removed the solid adjuvant material that is insoluble in water among the artificial Calculus Bovis.Particularly the key component cholic acid with artificial Calculus Bovis in the general solid particle agent uses glacial acetic acid or citric acid effectively to extract, and the dissolubility that makes general solid particle agent add the hot water lithocholic acid is brought up to more than 95% by 77%.The test correction data sees the following form.In the test in employed artificial Calculus Bovis's raw material cholic acid content be 15.40%.
We have bought the pediatric paracetamol,atificial cowbezoar and chlorphenamine maleate granule agent of relevant producer on market, dissolving under 60 ℃ of hot water, and the dissolution rate that goes out cholic acid with artificial Calculus Bovis's cubage in the prescription component is 83.2%.
It is thus clear that the present invention uses the glacial acetic acid of constant volume 0.1%, can the cholic acid among the artificial Calculus Bovis be extracted 92.2%, extract cholic acid with glacial acetic acid greater than constant volume 0.5%, extraction ratio is more than 95%, and the result does not have significant difference.Result of the test proves absolutely, uses the glacial acetic acid of constant volume 0.7% to be enough to fully the cholic acid among the artificial Calculus Bovis extracted.
3, improved drug bioavailability.
The oral administration solution of compound preparation of the present invention makes the active component dispersion of medicine big, absorbs soon, and effect has improved drug bioavailability rapidly.Particularly the main active component cholic acid among the artificial Calculus Bovis is brought up to more than 95% by 77% dissolubility of solid particle, has improved the human bioavailability of cholic acid.
4, strengthened curative effect of medication.
It is faster that the oral administration solution dosage form makes that the patient takes post-absorption, and the active component of product can get into blood circulation rapidly, has reached effective Mlc in the short period of time, makes the product curative effect more remarkable.
5, untoward reaction is few.
Because the present invention processes clarifying liquid with acetaminophen, artificial Calculus Bovis, chlorphenamine maleate and glacial acetic acid (perhaps citric acid) through dissolving; Filter out some that exist in the raw material and be insoluble in the solid adjuvant material of water; Make that the active component in the medicine is more pure, avoided because of untoward reaction such as feeling sick of causing of the adjuvant in the solid preparation, vomitings.
6, taking convenience.
The size of its dosage of oral administration solution of the present invention's preparation is prone to regulate, and is easy to control, takes more convenient.The present invention is the oral administration solution dosage form, uses correctives and coloring agent, can be made into the pharmaceutical preparation (such as the Fructus Fragariae Ananssae flavor of children enjoy) of different taste, different colours, is easy to children's and swallows, and is more suitable for the child administration in disease.
The specific embodiment:
Further specify content of the present invention through following embodiment, but range of application of the present invention is not limited to following instance at present.
Embodiment 1,
Inventory is acetaminophen 12.5g, artificial Calculus Bovis 0.5g and chlorphenamine maleate 0.05g, glacial acetic acid 7ml (7.34g), potassium sorbate 2g.
1) uses glacial acetic acid 7ml, artificial Calculus Bovis 0.5g is dissolved fully (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving), stirred 30 minutes to 1 hour; Leave standstill; With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 12.5g of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.05g of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2g after stirring successively, to be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000ml.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 2,
Inventory is acetaminophen 12.5kg, artificial Calculus Bovis 0.5kg and chlorphenamine maleate 0.05kg, glacial acetic acid 7L (7.34kg), potassium sorbate 2kg.
1) uses glacial acetic acid 7L, artificial Calculus Bovis 0.5Kg is dissolved fully (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving), stirred 30 minutes to 1 hour; Leave standstill; With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 12.5Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.05Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2Kg after stirring successively, to be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 3,
Inventory is acetaminophen 125kg, artificial Calculus Bovis 5kg and chlorphenamine maleate 0.5kg, glacial acetic acid 70L (73.4kg), potassium sorbate 20kg.
1) uses glacial acetic acid 70L, artificial Calculus Bovis 5Kg is dissolved fully (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving), stirred 30 minutes to 1 hour; Leave standstill; With 0.45 and 0.2 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 125Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.5Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 20Kg after stirring successively, to be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 4,
Inventory is acetaminophen 12.5kg, artificial Calculus Bovis 0.5kg and chlorphenamine maleate 0.05kg, glacial acetic acid 10L (10.49kg), potassium sorbate 2kg.
1) uses glacial acetic acid 10L, artificial Calculus Bovis 0.5Kg is dissolved fully (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving), stirred 30 minutes to 1 hour; Leave standstill; With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 12.5Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.05Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2Kg after stirring successively, to be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 5,
Inventory is acetaminophen 0.5kg, artificial Calculus Bovis 0.01kg and chlorphenamine maleate 0.001kg, glacial acetic acid 0.05L (0.052kg), potassium sorbate 2kg.
1) uses glacial acetic acid 0.05L, artificial Calculus Bovis 0.01Kg is dissolved fully (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving), stirred 30 minutes to 1 hour; Leave standstill; With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 0.5Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.001Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2Kg after stirring successively, to be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 6,
Inventory is acetaminophen 12.5kg, artificial Calculus Bovis 0.5kg and chlorphenamine maleate 0.05kg, citric acid 10kg, potassium sorbate 2kg.
1) uses citric acid 10kg,, artificial Calculus Bovis 0.5Kg is dissolved fully (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving) with the dissolving of 10L purified water, stirred 30 minutes to 1 hour; Leave standstill; With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 12.5Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.05Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2Kg after stirring successively, to be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 7,
Inventory is acetaminophen 12.5kg, artificial Calculus Bovis 0.5kg and chlorphenamine maleate 0.05kg, glacial acetic acid 7L (7.34kg), 5kg tween 80, potassium sorbate 2kg.
1) uses glacial acetic acid 7L, add the 5kg tween 80, artificial Calculus Bovis 0.5Kg is dissolved fully (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving), stirred 30 minutes to 1 hour; Leave standstill; With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 12.5Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.05Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2Kg after stirring successively, to be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 8,
Inventory is acetaminophen 12.5kg, artificial Calculus Bovis 0.5kg and chlorphenamine maleate 0.05kg, glacial acetic acid 7L (7.34kg), potassium sorbate 2kg, sucrose 100kg.
1) uses glacial acetic acid 7L, artificial Calculus Bovis 0.5Kg is dissolved fully (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving), stirred 30 minutes to 1 hour; Leave standstill; With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 12.5Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.05Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2Kg after stirring successively, sucrose 100kg is to be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 9,
Inventory is acetaminophen 12.5kg, artificial Calculus Bovis 0.5kg and chlorphenamine maleate 0.05kg, glacial acetic acid 7L (7.34kg), potassium sorbate 2kg, Aspartane 10kg.
1) uses glacial acetic acid 7L, artificial Calculus Bovis 0.5Kg is dissolved fully (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving), stirred 30 minutes to 1 hour; Leave standstill; With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 12.5Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.05Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2Kg after stirring successively, Aspartane 10kg is to be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 10,
Inventory is acetaminophen 12.5kg, artificial Calculus Bovis 0.5kg and chlorphenamine maleate 0.05kg, glacial acetic acid 7L (7.34kg), potassium sorbate 2kg, Aspartane 8kg, strawberry essence 0.5kg.
1) uses glacial acetic acid 7L, artificial Calculus Bovis 0.5Kg is dissolved fully (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving), stirred 30 minutes to 1 hour; Leave standstill; With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 12.5Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.05Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2Kg after stirring successively, Aspartane 8kg, strawberry essence 0.5kg is to be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 11,
Inventory is acetaminophen 12.5kg, artificial Calculus Bovis 0.5kg and chlorphenamine maleate 0.05kg, glacial acetic acid 7L (7.34kg), 5kg tween 80, potassium sorbate 2kg, Aspartane 5kg, Fructus Citri tangerinae essence 0.5kg.
1) use glacial acetic acid 7L, the 5kg tween 80 dissolves artificial Calculus Bovis 0.5Kg (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving) fully, stirs 30 minutes to 1 hour; Leave standstill; With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 12.5Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.05Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2Kg after stirring successively, Aspartane 5kg, Fructus Citri tangerinae essence 0.5kg is to be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 12,
Inventory is acetaminophen 12.5kg, artificial Calculus Bovis 0.5kg and chlorphenamine maleate 0.05kg, glacial acetic acid 7L (7.34kg), potassium sorbate 2kg, sucrose 100kg, strawberry essence 0.5kg.
1) uses glacial acetic acid 7L, artificial Calculus Bovis 0.5Kg is dissolved fully (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving), stirred 30 minutes to 1 hour; Leave standstill; With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 12.5Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.05Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2Kg after stirring successively, sucrose 100kg, strawberry essence 0.5kg is to be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 13,
Inventory is acetaminophen 12.5kg, artificial Calculus Bovis 0.5kg and chlorphenamine maleate 0.05kg, and glacial acetic acid 7L (7.34kg), tartaric acid 5kg, potassium sorbate 2kg, the 5kg tween 80, sucrose 50kg, strawberry essence 0.5kg.
1) use glacial acetic acid 7L, the 5kg tween 80 dissolves artificial Calculus Bovis 0.5Kg (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving) fully, stirs 30 minutes to 1 hour; Add tartaric acid 5kg (using the 5L water dissolution in advance), stir, evenly.Leave standstill.With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 12.5Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.05Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2Kg after stirring successively, sucrose 50kg, strawberry essence 0.5kg stirs and makes dissolving, mix homogeneously.To be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 14,
Inventory is acetaminophen 12.5kg, artificial Calculus Bovis 0.5kg and chlorphenamine maleate 0.05kg, glacial acetic acid 7L (7.34kg), citric acid 5kg; Ethanol 4L, potassium sorbate 2kg, 5kg tween 80; Sucrose 50kg, strawberry essence 0.5kg, red No. 3 0.1kg of FD&.
1) use glacial acetic acid 7L, citric acid 5kg (using the water dissolution of 5L in advance), the 5kg tween 80, ethanol 4L dissolves artificial Calculus Bovis 0.5Kg (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving) fully, stirs 30 minutes to 1 hour; Leave standstill.With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 12.5Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.05Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2Kg after stirring successively, sucrose 50kg, strawberry essence 0.5kg, red No. 3 0.1kg of FD& stir and make dissolving, mix homogeneously.To be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Embodiment 15,
Inventory is acetaminophen 12.5kg, artificial Calculus Bovis 0.5kg and chlorphenamine maleate 0.05kg, glacial acetic acid 7L (7.34kg), tartaric acid 5kg; Glycerin 4L, potassium sorbate 2kg, 5kg tween 80; Sucrose 50kg, strawberry essence 0.5kg, red No. 3 0.1kg of FD&.
1) use glacial acetic acid 7L, the 5kg tween 80 dissolves artificial Calculus Bovis 0.5Kg (room temperature gets final product, also can 60 ℃～80 ℃ heating for dissolving) fully, stirs 30 minutes to 1 hour; Add tartaric acid 5kg (using the 5L water dissolution in advance), glycerin 4L, stirring and dissolving is even, leaves standstill.With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution.
2) in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen 12.5Kg of inventory, be stirred to abundant dissolving.
3) the chlorphenamine maleate 0.05Kg of adding inventory in the material-compound tank that dissolves acetaminophen fully stirs, and is cooled to room temperature.
4) in material-compound tank, add 1) in the settled solution that obtains, fully stir, add potassium sorbate preservative 2Kg after stirring successively, sucrose 50kg, strawberry essence 0.5kg, red No. 3 0.1kg of FD& stir and make dissolving, mix homogeneously.To be stirred well to the solution mix homogeneously behind the purified water standardize solution 1000L solution.Filter membrane cascade filtration with 0.45 and 0.22 micron.
Fill becomes 5ml/ to prop up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution of 100ml/ bottle or 120ml/ bottle.
Claims (5)
1. pediatric paracetamol oral solution, it is characterized in that mainly by following material by weight, the volume component forms:
Be settled to 1000 parts with purified water;
Its preparation method is:
1. use the glacial acetic acid of prescription inventory, the artificial Calculus Bovis of inventory is dissolved fully, stir 0.5～12h; Leave standstill; With 0.45 and 0.22 micron filter membrane cascade filtration, must clarify yellow or yellow solution;
2. in material-compound tank, add an amount of purified water, be heated to preference temperature, add the acetaminophen of inventory, be stirred to abundant dissolving;
3. in the material-compound tank that dissolves acetaminophen fully, add the chlorphenamine maleate of inventory, stir, be cooled to room temperature;
4. the settled solution that obtains in material-compound tank, adding 1. fully stirs, and adds cosolvent, stabilizing agent, antiseptic, correctives and coloring agent after stirring successively, to be stirred well to the solution mix homogeneously behind the purified water standardize solution; Filter membrane cascade filtration with 0.45 and 0.22 micron;
5. get intermediate check pH value, pH value is that 2.0-6.5 is qualified;
6. after the assay was approved, fill is that 5ml/ props up or 10ml/ props up or 20ml/ props up or the pediatric paracetamol oral solution finished product of 100ml/ bottle or 120ml/ bottle.
2. pediatric paracetamol oral solution according to claim 1, it is characterized in that by following material by weight, the volume component forms:
3. pediatric paracetamol oral solution according to claim 1, it is characterized in that by following material by weight, the volume component forms:
4. pediatric paracetamol oral solution according to claim 1, it is characterized in that by following material by weight, the volume component forms:
5. pediatric paracetamol oral solution according to claim 1, it is characterized in that by following material by weight, the volume component forms:
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Non-Patent Citations (2)
| Title |
|---|
| 刘养清等.胆酸.《动物胆汁理化特性及药用》.化学工业出版社,2002,(第1版),155. * |
| 国家药典委员会编.小儿氨酚黄那敏颗粒.《国家药品西药标准(化学药品地方标准上升国家标准第三册)》.2002,第53页. * |
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