CN109381426A - A kind of ibuprofen oral spray and preparation method thereof - Google Patents
A kind of ibuprofen oral spray and preparation method thereof Download PDFInfo
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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Abstract
The invention belongs to technical field of medicine, it is related to a kind of ibuprofen oral spray and preparation method thereof.Specifically, the oral spray includes brufen, solvent, cosolvent, corrigent, odor mask and strong olfactory agent, it can be made by the preparation method included the following steps: 1) prepare brufen/cosolvent mixtures；2) it prepares and rectifys olfactory agent/flavoring agent solution；3) mixed solution is prepared using strong olfactory agent/flavoring agent solution and brufen/cosolvent mixtures；4) it adds odor mask and solvent prepares finished product.Main ingredient concentration in oral spray of the invention is higher, and single oral dose is small, and medication is convenient, rapid-action, bioavilability is high, improves the safety and compliance of pediatric drugs, and the production craft step of preparation is simple, and products obtained therefrom is quality controllable, is suitable for industrialized production.
Description
Technical field
The invention belongs to technical field of medicine, are related to a kind of ibuprofen oral spray, especially paediatrics cloth Lip river
The preparation method of fragrant oral spray and the oral spray.
Background technique
As a specific group, mood when due to children's morbidity is difficult to control, to the administration modes such as having an injection, be infused again
Lack compliance, therefore very headache is made us always in children's administration.Cat fever is one of most common disease of children.Investigation is aobvious
Show, the annual disease incidence that 0 to the 12 year old age bracket children in China suffer from cat fever adds up to 2.72 times.China has 200,000,000 at present
Whatever amount it is virgin, it is larger for the demand of analgesic-antipyretic, therefore form very huge pediatric drugs consumption market.
In analgesic-antipyretic field, there are still problems for many drugs.For example, the side effect of aspirin is big, it is main to show
For hemorrhage of gastrointestinal tract, decrease of platelet, children's Reye syndrome (Reye ' s syndrome, RS) can be also caused when serious, is died of illness
Rate is up to 30%.Currently, clear stipulaties 16 years old or less children of Britain disable aspirin, and used in China's Pediatric Clinic
Also tend in medicine superseded.In addition, bring down a fever effect and the dose proportional of paracetamol (paracetamol), when dosage is excessive
It can cause the toxic side effects such as hepatotoxicity wind agitation.
Brufen (Ibuprofen) is the non-steroid anti-inflammatory drug (NSAID) that a clinical line uses, antipyretic, ease pain, disappear
Scorching function well, adverse reaction is small, and oral absorption is rapid, has small (especially to liver, kidney, blood using safe, toxic effect
Toxic effect is fairly small), the advantages that curative effect is high.
Currently, the dosage form developed for brufen mainly includes tablet, capsule, injection, granule, suspension
Deng wherein paediatrics often uses granule and suspension.However, either granule or suspension, all presence administration are difficult, quantitative
The problems such as inaccuracy, oral dose are big, it is slow to work, poor taste, is unable to satisfy the primary demand of pediatric drugs to a certain extent.
Therefore, find a kind of convenient drug administration, oral dose is small, action is rapid, suitable for pediatric drugs brufen novel form have it is important
Clinical meaning.
Summary of the invention
Problems to be solved by the invention
Since existing ibuprofen dosage form is unsuitable for pediatric administration mostly, the compliance of children is poor, and exists
The problems such as oral dose is big, it is slow to work, poor taste, thus the present invention by provide a kind of completely new ibuprofen oral spray come
Overcome the above problem.
The solution to the problem
On the one hand, the present invention provides a kind of ibuprofen oral spray, the oral spray includes brufen, molten
Agent, cosolvent, corrigent, odor mask and strong olfactory agent.
Preferably, in above-mentioned ibuprofen oral spray, 300~500g cloth Lip river is contained in every 1000ml oral spray
Sweet smell, 150~350g cosolvent, 0.1~25 corrigent, 150~250g odor mask and 0.1~3g rectify olfactory agent.
It is highly preferred that containing 360~440g cloth in every 1000ml oral spray in above-mentioned ibuprofen oral spray
Ibuprofen, 220~280g cosolvent, 1~15g corrigent, 180~230g odor mask and 0.5~1.5g rectify olfactory agent.
In above-mentioned ibuprofen oral spray, the cosolvent in inorganic base, organic base, basic amino acid extremely
It is few any.
Preferably, the cosolvent in above-mentioned ibuprofen oral spray is selected from L-arginine, L-lysine, L- group ammonia
At least any one in acid, more preferable L-arginine.
In above-mentioned ibuprofen oral spray, the corrigent selected from natural flavorant, synthesis corrigent at least
It is any.
Preferably, the corrigent in above-mentioned ibuprofen oral spray is selected from Sucralose, stevioside, A Sipa
Smooth, at least any one in sodium chloride, more preferable Sucralose.
In above-mentioned ibuprofen oral spray, the odor mask at least appointing in organic acid, glycerol and its esters
It is a kind of.
Preferably, the odor mask in above-mentioned ibuprofen oral spray in glycerol, lactic acid, tartaric acid at least
It is any, more preferable glycerol.
In above-mentioned ibuprofen oral spray, the strong olfactory agent in volatility terpene, fruity flavor, carbohydrate extremely
It is few any.
Preferably, the strong olfactory agent in above-mentioned ibuprofen oral spray is in menthol, glucose, flavoring apple essence
At least any one, more preferable menthol.
In above-mentioned ibuprofen oral spray, the solvent is water, preferably purified water.
Preferably, above-mentioned ibuprofen oral spray is solution-type oral spray.
On the other hand, the present invention also provides the preparation methods of above-mentioned ibuprofen oral spray comprising the following steps:
1) brufen and cosolvent are mixed, obtains brufen/cosolvent mixtures；
2) suitable solvent is measured, is added rectifys olfactory agent and corrigent thereto, obtains rectifying olfactory agent/flavoring agent solution；
3) brufen/cosolvent obtained in step 1) is added in strong olfactory agent/flavoring agent solution obtained into step 2)
Mixture obtains mixed solution；
4) odor mask is added in mixed solution obtained into step 3), then add solvent to get.
Preferably, above-mentioned preparation method carries out under agitation.
Preferably, above-mentioned preparation method further includes insoluble matter filtering, content detection, packing, labeling and packaging step.
The effect of invention
The present invention develops the oral spray suitable for pediatric drugs using brufen as model drug, to improve brufen
Solubility is point of penetration, by will the brufen containing carboxyl in conjunction with as cosolvent, it is lower to solve solubility in water
Problem.With existing pediatric pharmaceuticals ibuprofen suspension (main ingredient concentration be 2%~4%, single oral dose be 1.25~
It 10ml) compares, the main ingredient concentration in oral spray of the invention is higher (up to 40%), and single oral dose is smaller (only
0.125~1ml), facilitate while multiple dosing that also convenient for children is swallowed, medication is more convenient, works faster (faster than tablet 4
Times), bioavilability is higher.Cooperate dosing device, can be realized accurate administration, improve pediatric drugs safety.This
Outside, the production craft step of oral spray of the invention is simple, convenient, products obtained therefrom it is quality controllable, be suitable for industrializing
Production provides a kind of completely new dosage form selection for the Pediatric Clinic medication of brufen, has important economic value and society
Value.
Specific embodiment
Compared to other dosage forms, oral spray has the advantage that (1) drug pack in closed container, can be kept
Cleaning and germ-free condition, reduce the contaminated probability of drug；In addition, the condition of being protected from light has since closed container is usually opaque
Conducive to the stability for improving drug；(2) after stopping using, remaining drug is remained in closed container, is not easy to pollute；
(3) easy to use, administration can be completed in a spray of opening one's mouth, suitable for people of all ages, helps to improve the compliance of patient, especially suitable
In OTC drug；(4) this product is administered in the form of oral spray, is still able to maintain after mixing with the saliva in oral cavity very molten
The state of liquid, compared to peroral dosage forms such as tablet, capsules, this product is after taking without processes such as disintegration, dissolutions, it is thus possible to
Rapid-onset；(5) oral spray is commonly provided with special quantitative valve, and dosage is accurate, is conducive to standardized drug's behavior,
Improve drug safety.
Based on this, the present invention provides a kind of ibuprofen oral sprays comprising brufen, solvent, cosolvent, flavoring
Agent, odor mask and strong olfactory agent.
In a preferred embodiment, in every above-mentioned oral spray of 1000ml containing 300~500g brufen,
150~350g cosolvent, 0.1~25 corrigent, 150~250g odor mask and 0.1~3g rectify olfactory agent.
In a further preferred embodiment, in every above-mentioned oral spray of 1000ml containing 360~440g brufen,
220~280g cosolvent, 1~15g corrigent, 180~230g odor mask and 0.5~1.5g rectify olfactory agent.
Unless otherwise indicated, the term " spray " occurred in the context of the present invention refer to medical fluid is filled in it is special
In device, preparation that when use is released content by the pressure of manual pump in the form of mist etc..It is drawn according to content form
Point, spray can be divided into solution-type, emulsion-type and suspension ability.According to using position to divide, spray can be divided into oral spray
And nasal mist.Whether quantitative according to administration, spray can be divided into metered dose agent and non-quantitation spray.Preferably, originally
The ibuprofen oral spray of invention is that solution-type quantifies oral spray.
Other than the brufen as main active, above-mentioned ibuprofen oral spray further includes other auxiliary materials,
Such as solvent, cosolvent, corrigent, odor mask, strong olfactory agent etc..
Unless otherwise indicated, the term " cosolvent " occurred in the context of the present invention be refer in a solvent with indissoluble
Property drug form soluble intermolecular complex, associated matter or double salt etc., to increase the dissolution of insoluble drug in a solvent
The auxiliary material of degree, for example, can with acid indissoluble substance at the alkaline matter of salt, with alkaline indissoluble substance at the acidic materials, logical of salt
It crosses hetero atom and forms complex compound or the substance of associated matter etc..In above-mentioned ibuprofen oral spray, due to as main cloth
Ibuprofen is acid indissoluble substance, therefore required cosolvent is selected from containing the group that can be reacted with the carboxyl in brufen structure
Substance at least any one, these substances include inorganic base (such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate,
Sodium bicarbonate, saleratus, ammonia, ammonium carbonate, ammonium hydrogen carbonate etc.), organic base (such as methylamine, dimethylamine, trimethylamine, ethamine, two
Ethamine, triethylamine, diisopropylethylamine, ethylenediamine, meglumine, Portugal's ethamine, triethanolamine, triethylene diamine etc.) and alkaline ammonia
Base acid (including L-arginine, L-lysine, L-Histidine etc.).
In a preferred embodiment, the cosolvent in above-mentioned ibuprofen oral spray is selected from L-arginine, L-
At least any one in lysine, L-Histidine, preferably L-arginine.The alkaline ammonias such as L-arginine, L-lysine, L-Histidine
Base acid due to there are the basic groups such as guanidine radicals, amino, imidazole radicals can be with the carboxyl in brufen at salt, and then increase brufen
Solubility in water, to play solubilization-aid effect.
Unless otherwise indicated, the term " corrigent " occurred in the context of the present invention is to refer to improve pill taker to medicine
The tolerance of object disagreeable taste makes pill taker be not likely to produce the auxiliary material of unhappy sense, including natural flavorant (such as sucrose, grape
Syrup, fructose syrup, honey, stevioside, sodium chloride, potassium chloride etc.) and synthesis corrigent (Sucralose, aspartame, saccharin
Sodium, honey element, protein sugar, acesulfame potassium etc.).
In a preferred embodiment, the corrigent in above-mentioned ibuprofen oral spray is selected from Sucralose, sweet tea
At least any one in chrysanthemum glycosides, aspartame, preferably Sucralose.The corrigents such as Sucralose, stevioside, aspartame make to take
The taste bud of medicine person can perceive sugariness easily, give pill taker's bring unhappy sense to alleviate the smell of drug itself.
Unless otherwise indicated, the term " odor mask " occurred in the context of the present invention refers to cover drug itself
Disagreeable taste (such as strong bitter taste, astringent taste or acid etc.), to make the imperceptible auxiliary material of pill taker, including organic acid
(such as tannic acid, lactic acid, citric acid, tartaric acid etc.) and glycerol and its esters (such as glycerol, glycerin monostearate, distearyl
Acid glyceride, triglyceride etc.).
In a preferred embodiment, the odor mask in above-mentioned ibuprofen oral spray is selected from glycerol, lactic acid, wine
Stone acid at least any one, preferably glycerine.Glycerol can be miscible with water, and can generate certain solubilising to brufen and imitate
Fruit helps to further increase the solubility of main ingredient in water, avoids and muddiness, crystallization etc. occurs now because main ingredient solubility is low
As.
Unless otherwise indicated, the term " strong olfactory agent " occurred in the context of the present invention is to refer to improve pill taker to medicine
The tolerance of object bad smell makes pill taker be not likely to produce the auxiliary material of unhappy sense, including volatility terpene (such as menthol, dragon
Brain, camphor etc.), fruity flavor (such as flavoring apple essence, orange essence, strawberry essence, flavoring banana essence etc.) and carbohydrate (such as grape
Sugar, fructose etc.).
In a preferred embodiment, the strong olfactory agent in above-mentioned ibuprofen oral spray is selected from menthol, grape
Sugar, at least any one in flavoring apple essence, preferably menthol.Since menthol itself has heat-clearing, removing toxic substances, relieving sore-throat, analgesic
Effect, therefore brufen can be cooperated to play synergistic antipyretic-antalgic effect.In addition, menthol also has certain suppression
Bacterium effect, no longer needs to additionally add preservative ingredient.
Unless otherwise indicated, the term " solvent " occurred in the context of the present invention refers to for dissolving or dispersing to constitute spray
The main ingredient of mist agent and the liquid substance of auxiliary material, for example, water for dissolving or dispersing larger polar component, for dissolving or dispersing
The ethyl alcohol of middle polarity ingredient and kerosene etc. for dissolving or dispersing smaller polar component.
Since kerosene can generate stimulation to mucous membrane, it is not suitable for oral spray or nasal mist
Solvent.In addition, although ethyl alcohol is the good solvent of brufen, but in view of the medication group of oral spray of the invention is mainly
Children or child need the use of strict control ethyl alcohol.Therefore, in a preferred embodiment, above-mentioned ibuprofen oral
Solvent in spray is water, preferably purified water.
In a preferred embodiment, above-mentioned ibuprofen oral spray is solution-type oral spray.Main ingredient cloth
The mixture of the auxiliary materials such as ibuprofen and cosolvent can form uniform, stable true solution in a solvent.
On the other hand, the present invention also provides the preparation methods of above-mentioned ibuprofen oral spray comprising the following steps:
1) brufen and cosolvent are mixed, obtains brufen/cosolvent mixtures；
2) suitable solvent is measured, is added rectifys olfactory agent and corrigent thereto, obtains rectifying olfactory agent/flavoring agent solution；
3) brufen/cosolvent obtained in step 1) is added in strong olfactory agent/flavoring agent solution obtained into step 2)
Mixture obtains mixed solution；
4) odor mask is added in mixed solution obtained into step 3), then add solvent to get.
In a preferred embodiment, each step in the preparation method carries out under agitation, favorably
Uniform mixture or uniform solution are formed in different component.
In a preferred embodiment, the preparation method further includes insoluble matter filtering, content detection, packing, patch
Mark and packaging step.
Carry out the technical solution during the present invention is further explained below in conjunction with specific embodiment.It should be understood that following
Embodiment is only used for the explanation and illustration present invention, and is not intended to limit the scope of protection of the present invention.In addition, unless otherwise saying
Bright, instrument, material used in the following example, reagent etc. can be obtained by routine business means.
Embodiment 1: the preparation of ibuprofen oral spray.
The preparation of mouth spraying agent is carried out according to the prescription in table 1.
The formula composition and dosage of mouth spraying agent in 1. the present embodiment of table
Specific preparation process is as follows:
1) brufen of recipe quantity and L-arginine are mixed, it is spare；
2) suitable purified water (about 90-100ml) is measured, the menthol and Sucralose of recipe quantity are added thereto, stirs
It mixes to whole dissolutions；
3) system in step 1) under agitation, is added in corrigent obtained and the aqueous solution of strong olfactory agent into step 2)
The mixture of the brufen and cosolvent that obtain, stirring to whole dissolutions；
4) glycerol of recipe quantity is added in mixed solution obtained into step 3), moisturizing to 1000ml stirs evenly, i.e.,
?.
Above-mentioned oral spray filters through husky formula, semi-finished product content detection, packing are (filling into aerosol container, and be equipped with
Metering atomizing spray pump, dispensed loading amount be 1.5 or 3.0ml/ bottle), labeling, pack etc. processes be finally made dosage form.
Its composition is optimized in the oral spray of the present embodiment, passes through addition Sucralose, glycerol and thin
The flavorings such as lotus brain/taste masking/rectify and smell reagent, solve bitter taste and pungent that drug itself is shown, substantially improve the use of children
Drug compliance；Meanwhile glycerol can play main ingredient brufen solubilization, menthol can cooperate with performance antipyretic with brufen
Analgesic activity (is better than Genpril), can also play antibacterial preservative efficacy, composition is reasonable, and effect is comprehensive.
Embodiment 2: the preparation of ibuprofen oral spray.
The preparation of mouth spraying agent is carried out according to the prescription in table 2.
The formula composition and dosage of mouth spraying agent in 2. the present embodiment of table
Specific preparation process is as follows:
1) brufen of recipe quantity and L-arginine are mixed, it is spare；
2) suitable purified water (about 90-100ml) is measured, the menthol and Sucralose of recipe quantity are added thereto, stirs
It mixes to whole dissolutions；
3) system in step 1) under agitation, is added in corrigent obtained and the aqueous solution of strong olfactory agent into step 2)
The mixture of the brufen and cosolvent that obtain, stirring to whole dissolutions；
4) glycerol of recipe quantity is added in mixed solution obtained into step 3), moisturizing to 1000ml stirs evenly, i.e.,
?.
Above-mentioned oral spray filters through husky formula, semi-finished product content detection, packing are (filling into aerosol container, and be equipped with
Metering atomizing spray pump, dispensed loading amount be 1.5 or 3.0ml/ bottle), labeling, pack etc. processes be finally made dosage form.
Embodiment 3: the preparation of ibuprofen oral spray.
The preparation of mouth spraying agent is carried out according to the prescription in table 3.
The formula composition and dosage of mouth spraying agent in 3. the present embodiment of table
Specific preparation process is as follows:
1) brufen of recipe quantity and L-arginine are mixed, it is spare；
2) suitable purified water (about 200-300ml) is measured, menthol, flavoring apple essence, the chlorine of recipe quantity are added thereto
Change sodium and Sucralose, stirring to whole dissolutions；
3) system in step 1) under agitation, is added in corrigent obtained and the aqueous solution of strong olfactory agent into step 2)
The mixture of the brufen and cosolvent that obtain, stirring to whole dissolutions；
4) glycerol of recipe quantity is added in mixed solution obtained into step 3), moisturizing to 1000ml stirs evenly, i.e.,
?.
Above-mentioned oral spray filters through husky formula, semi-finished product content detection, packing are (filling into aerosol container, and be equipped with
Metering atomizing spray pump, dispensed loading amount be 1.5 or 3.0ml/ bottle), labeling, pack etc. processes be finally made dosage form.
Embodiment 4: the preparation of ibuprofen oral spray.
The preparation of mouth spraying agent is carried out according to the prescription in table 4.
The formula composition and dosage of mouth spraying agent in 4. the present embodiment of table
Specific preparation process is as follows:
1) brufen of recipe quantity and L-lysine are mixed, it is spare；
2) suitable purified water (about 200-300ml) is measured, menthol, flavoring apple essence, the chlorine of recipe quantity are added thereto
Change sodium and stevioside, stirring to whole dissolutions；
3) system in step 1) under agitation, is added in corrigent obtained and the aqueous solution of strong olfactory agent into step 2)
The mixture of the brufen and cosolvent that obtain, stirring to whole dissolutions；
4) glycerol of recipe quantity is added in mixed solution obtained into step 3), moisturizing to 1000ml stirs evenly, i.e.,
?.
Above-mentioned oral spray filters through husky formula, semi-finished product content detection, packing are (filling into aerosol container, and be equipped with
Metering atomizing spray pump, dispensed loading amount be 1.5 or 3.0ml/ bottle), labeling, pack etc. processes be finally made dosage form.
Experimental example 1: ibuprofen oral spray is in the intracorporal pharmacodynamic study of mouse.
This experimental example has separately verified in the embodiment 3 of different dosing dosage ibuprofen oral spray obtained to mouse
Analgesic activity and embodiment 1 in two kinds of dosage forms of oral spray and tablet obtained the timeliness of mouse analgesic activity is closed
System, it is described that the specific method is as follows.
4 week old kunming mices 40, average weight 20g, half male and half female are randomly divided into four groups, and every group 10, respectively
Blank control group, low dose group, middle dose group and high dose group.After the modeling of heat radiation tail-flick test, low, middle and high dose groups
Mouse is respectively according to 50,75 and 100mgkg-1Dosage direct oral cavity grant brufen mouth spraying agent, blank control group is then granted together
Isodose purified water, result is as shown in table 5 and table 6.
The ibuprofen oral spray of 5. different dosing dosage of table is in the intracorporal pharmacodynamic result of mouse
By the data in table 5 it is found that low dose group does not show apparent analgesic activity, and middle dose group and high dose group
All have analgesic effect.The PMPA (maximum analgesia percentage) of high dose group is 38.7%, and the PMPA of middle dose group is 28.3%,
Illustrate that the analgesic activity of high dose is better than middle dosage, analgesic activity enhances with the increase of dosage.
The Motrin of 6. different dosage forms of table is in the intracorporal exercising result of mouse
By the data in table 6 it is found that for the different dosing dosage form of brufen, in same dosage (100mg
kg-1) under the conditions of, the PMPA of oral spray is far longer than tablet, illustrates that oral spray is more stronger than the analgesic activity of tablet.Separately
Outside, the T of oral spraymax(peak time) is only the 1/4 of tablet, illustrates that oral spray works faster than tablet.
Experimental example 2: ibuprofen oral spray is in the intracorporal pharmacokinetic studies of beasle dog.
This experimental example detects the determination of ibuprofen in Dog Plasma by HPLC method, and then verifies in embodiment 3 and be made
Two kinds of dosage forms of oral spray and tablet in the intracorporal pharmacokinetics behavior of beasle dog, it is described that the specific method is as follows.
10 monthly age beasle dogs 8, average weight 9.5kg, half male and half female are randomly divided into two groups, and every group 4, two groups of dogs
Ibuprofen oral spray (200mg/ dog, in terms of drug content) obtained and Genpril in embodiment 1 are only given respectively
After (200mg/ dog, in terms of drug content), adopted at small saphenous vein on the outside of the hind leg in 30min, 1h, 2h, 4h, 8h, 16h and for 24 hours
Collect blood sample, uses the blood concentration after the measurement administration of HPLC analysis method after carrying out blood plasma pretreatment, and calculate pharmacokinetics ginseng
Number, the results are shown in Table 7.
The Motrin of 7. different dosage forms of table is in the intracorporal Pharmacokinetic Results of beasle dog
By the data in table 7 it is found that ibuprofen oral spray is relative to the relative bioavailability of tablet
109.55% ± 19.59%.Statistical procedures, Analysis of variance discovery, AUC are carried out to two groups of pharmacokinetic parameters0-24h、
MRT0-24h、T1/2、CLz/F、CmaxDeng between oral spray and tablet, there was no significant difference (P > 0.05)；TmaxIt is sprayed in oral cavity
There are significant difference (P < 0.05), the T of oral spray group between mist agent and tabletmaxIt is significantly less than tablet group, peak time
It is about advanced by 1 hour, shows ibuprofen oral spray and Genpril bioequivalence, but oral spray action is more fast
Speed, more suitable for the needs of Pediatric Clinic treatment.
Claims (8)
1. a kind of ibuprofen oral spray, the oral spray includes brufen, solvent, cosolvent, corrigent, odor mask
With strong olfactory agent.
2. ibuprofen oral spray according to claim 1, it is characterised in that:
Contain 300~500g brufen, 150~350g cosolvent, 0.1~25 flavoring in oral spray described in every 1000ml
Agent, 150~250g odor mask and 0.1~3g rectify olfactory agent.
3. ibuprofen oral spray according to claim 1, it is characterised in that:
In oral spray described in every 1000ml containing 360~440g brufen, 220~280g cosolvent, 1~15g corrigent,
180~230g odor mask and 0.5~1.5g rectify olfactory agent.
4. ibuprofen oral spray according to any one of claim 1 to 3, it is characterised in that:
At least any one of the cosolvent in inorganic base, organic base, basic amino acid；
At least any one of the corrigent in natural flavorant, synthesis corrigent；
At least any one of the odor mask in organic acid, glycerol and its esters；
At least any one of the strong olfactory agent in volatility terpene, fruity flavor, carbohydrate.
5. ibuprofen oral spray according to any one of claim 1 to 3, it is characterised in that:
At least any one of the cosolvent in L-arginine, L-lysine, L-Histidine；
At least any one of the corrigent in Sucralose, stevioside, aspartame；
At least any one of the odor mask in glycerol, lactic acid, tartaric acid；
At least any one of the strong olfactory agent in menthol, glucose, flavoring apple essence.
6. ibuprofen oral spray according to any one of claim 1 to 3, it is characterised in that:
The solvent is water.
7. ibuprofen oral spray according to any one of claim 1 to 3, it is characterised in that:
The oral spray is solution-type oral spray.
8. the preparation method of ibuprofen oral spray according to any one of claim 1 to 7 comprising following step
It is rapid:
1) brufen and cosolvent are mixed, obtains brufen/cosolvent mixtures；
2) suitable solvent is measured, is added rectifys olfactory agent and corrigent thereto, obtains rectifying olfactory agent/flavoring agent solution；
3) brufen/cosolvent mixing obtained in step 1) is added in strong olfactory agent/flavoring agent solution obtained into step 2)
Object obtains mixed solution；
4) odor mask is added in mixed solution obtained into step 3), then add solvent to get.
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| CN111544384A (en) * | 2020-05-29 | 2020-08-18 | 北京联合大学 | Technology and preparation method of children ibuprofen over-the-counter drug |
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