CN103099807A - Compound zinc gluconate and ibuprofen oral-administration composition for covering bitter taste and improving ibuprofen dissolution - Google Patents
Compound zinc gluconate and ibuprofen oral-administration composition for covering bitter taste and improving ibuprofen dissolution Download PDFInfo
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- CN103099807A CN103099807A CN2011103604442A CN201110360444A CN103099807A CN 103099807 A CN103099807 A CN 103099807A CN 2011103604442 A CN2011103604442 A CN 2011103604442A CN 201110360444 A CN201110360444 A CN 201110360444A CN 103099807 A CN103099807 A CN 103099807A
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Abstract
The invention relates to the field of pharmaceutic preparation, and specifically relates to a compound zinc gluconate and ibuprofen oral-administration composition for covering bitter taste and improving ibuprofen dissolution check item, and a preparation method thereof. The compound zinc gluconate and ibuprofen oral-administration composition for covering bitter taste and improving ibuprofen dissolution is characterized by mainly comprising main drugs: 0.036-0.83 of high-sweetness sugar, 5-15 of filler, and 0.0006-0.0060 of surfactant. The preparation provided by the invention is good in taste and high in bioavailability; and the composition is blended with water before administration so that the compliance of patients is improved.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of Compound Zinc cloth oral formulations of covering bitterness and increase ibuprofen dissolution check item and preparation method thereof.
Background technology
Compound Zinc cloth granule is coldrex class OTC (over-the-counter).ibuprofen is for having antiinflammatory, analgesic, the NSAID (non-steroidal anti-inflammatory drug) of analgesic activity, it is a kind of inhibitor of prostaglandin, its curative effect and safety have obtained domestic and international many scholars' approval, it alleviates by suppressing Cycloxygenase (COX) inflammatory reaction that causes because of the prostaglandin gathering, heating and pain, can obviously suppress the arachidonic enzymes metabolism and generate prostaglandin E (PGE), can suppress tumor necrosis factor again, il-1, the release of the inflammatory mediators such as macrophage inflammatory protein (MIP), thereby the congested swelling that reduces inflammation, has obvious antipyretic effect.Ibuprofen toxicity is minimum in whole antipyretic analgesics, and has efficiently and bring down a fever fast, and the characteristics long and safety of holding time more are applicable to the extensive use of Pediatric Clinic.Zinc gluconate is dissociated into zinc ion in vivo, zinc is one of trace element of needed by human body, participate in the multiple important Enzyme Productions such as carbonic anhydrase, archaeal dna polymerase, the function of zinc enzyme in reinforcement, promote nucleic acid and proteolipin synthetic, induce the generation endogenous interferon, the cytophagous phagocytic activity of enhancing is arranged, play antiviral, antibacterial action.Many studies show that, zinc can improve child's immunity, particularly strengthen respiratory tract and gastral resistance, the effect that can play prevention infection and remove infective agent is to the generation of some commonly encountered diseases of child such as children's cold, diarrhoea, lower respiratory infection etc. with shorten the course of disease obvious effect is arranged.Chlorphenamine maleate is antihistaminic, can suppress histamine and 5-hydroxy tryptamine and discharge, and alleviates the symptom that anaphylaxis occurs, and alleviates the histologic lesion that inflammation on every side causes, and can alleviate the symptoms such as nasal obstruction that flu or influenza cause, watery nasal discharge, sneeze.So Compound Zinc cloth granule has good analgesic, analgesia, antiinflammatory, anti-allergic effects, can suppress the virus recurrences such as rhinovirus, herpes simplex virus, suppresses acidophil and discharges histamine.This preparation has the good effect of bringing down a fever, take rear antipyretic effect strong, longer duration, again without the possibility of bringing out haemolysis, and medical expense is not high, and mouthfeel is good, easily feeding, the advantage of easily accepting for vast parents of hospitalized children, a kind of one of the medicine safely and effectively the when while is also the symptom such as the caused heating of acute upper respiratory tract infection (being commonly called as flu), pharyngalgia, headache.
At present, the Compound Zinc cloth granule of list marketing does not have the ibuprofen dissolution check item at home, although can cover this bitterness, clinically, higher bioavailability is arranged not necessarily.
Ibuprofen in Compound Zinc cloth granule is insoluble drug, selects granule, before use with the suspension administration, can increase the contact area of medicine and gastro-intestinal Fluid, improves to absorb.Add comprehensive, careful, deep research carried out in dissolution in vitro test, more science, effectively estimate and improve bioavailability in body.
Dissolution Rate Testing refers to the stripping curve mensuration in many pH value dissolution medium, but not the mensuration of a medium, a time point, a limit.These means are for granule imitation medicine research and development and prescription screening, and for the success rate that improves Bioequivalence Test, and vital effect is also being brought into play in all kinds of change evaluations that might have influence on the medicine biological nature.Many stripping curves are granule " finger printing ".Dissolving-out technology is soul and the core place of solid preparation interior quality.By the strict demand to the dissolution experiment, abundant, scrutiny to preparation process have greatly been promoted; Inherent quality and the clinical efficacy of medicine have been promoted.
Thereby how can effectively overcome and cover bitterness, and improve the dissolution of medicine, be the key issue of Compound Zinc cloth granule.
Summary of the invention
The object of the invention is to disclose a kind ofly takes after mixing it with water before use, and mouthfeel is Compound Zinc cloth oral formulations preferably, covers the bitterness of principal agent by adding a certain proportion of high sweetness sugars and essence, then adds a certain proportion of surfactant to improve the dissolution of medicine.
Technical scheme of the present invention is as follows:
Compound Zinc cloth Orally administered composition of the present invention is characterized in that containing following component and weight ratio:
Principal agent: 1
High sweetness sugars: 0.036 ~ 0.083
Filler: 5 ~ 15
Surfactant: 0.0006 ~ 0.0060
Wherein: high sweetness sugars is selected from acesulfame potassium, steviosin, cyclamate, saccharin sodium, sucralose, aspartame.
Filler is selected from microcrystalline Cellulose, sucrose, lactose, mannitol, starch.
Surfactant is selected from sodium lauryl sulphate, tween 80, Arlacel-80.
Orally administered composition of the present invention also contains essence.
Orally administered composition of the present invention, the agent of dosage form preferred particulates.
When dosage form was granule, preferred component and weight ratio were:
Zinc gluconate 100g
Ibuprofen 150g
Chlorphenamine maleate 2g
Sodium lauryl sulphate 0.45g
Vanillin 15g
Steviosin 15g
With sucrose to 3000g
Its preparation method is:
1) preparation of wetting agent: all dissolve with the chlorphenamine maleate of appropriate purified water with recipe quantity, standby.
2) zinc gluconate, ibuprofen, sucrose are crossed respectively 60 mesh sieves, standby.
3) take zinc gluconate, ibuprofen, sodium lauryl sulphate, steviosin, vanillin and half amount by recipe quantity
The sucrose mix homogeneously, then add the sucrose mix homogeneously of remaining half amount.
4) add wetting agent soft material processed, cross 14 mesh sieve granules processed.
5) wet granular is dried to pellet moisture in 50 ℃ ± 5 ℃ and must not crosses 4.0%, crosses 14 mesh sieve granulate.
6) granule that granulate is good adds mixing in mixer, and intermediate is sub-packed in compound membrane bag after the assay was approved, i.e. Compound Zinc cloth granule.
Characteristics of the present invention are to use before use mixing in water for oral taking, and mouthfeel is better, can effectively overcome and cover bitterness, and improve the dissolution of medicine.
Formula of the present invention obtains through screening, and screening process is as follows:
1, the foundation of dosage form selection
Granule be applicable to oral solid formulation swallow inconvenience pediatric patient and seriously ill, lie on the back, the patient of the inconvenience of taking medicine such as pharyngolaryngitis is swollen, add correctives in dosage form, improve mouthfeel, be convenient to take.Ibuprofen in Compound Zinc cloth granule is insoluble drug, selects granule, before use with the suspension administration, can increase the contact area of medicine and gastro-intestinal Fluid, improves to absorb; Add high sweetness sugars in dosage form, improve mouthfeel, be convenient to take.Granule has that dosage is accurate, content is even, chemical stability is good, and production mechanization, automaticity are high, and cost is lower, absorption is very fast, carry, transport, storage and the advantage such as easy to use, so this dosage form is occupied absolute advantage on market.
2, the selection of high sweetness sugars
For the solid preparation of directly taking after mixing it with water, the quality of mouthfeel has determined directly whether the patient can accept to take this medicine.General sucrose or other nutrient sugar conventional amount used well principal agent cover bitterness, therefore need to add high sweetness sugars to overcome this defective.If but the amount that high sweetness sugars adds too much can cause having abnormal flavour, if very fewly can not cover the principal agent bitterness again, therefore, the consumption of the high sweetness sugars of screening is the key of dealing with problems.For determining the consumption of high sweetness sugars, adjust the ratio of high sweetness sugars, test, the results are shown in Table 1.
The selection result of the high sweetness sugars different amounts of table 1
| High sweetness sugars title | Consumption (pressing principal agent weight ratio 1 calculates) | Sugariness |
| Steviosin | 0.036 | Lighter, be detained on tongue fur without bitterness |
| Steviosin | 0.048 | Little light, be detained on tongue fur without bitterness |
| Steviosin | 0.060 | Sweeter, be detained on tongue fur without bitterness |
| Steviosin | 0.071 | Sweeter, be detained on tongue fur without bitterness |
| Steviosin | 0.083 | Very sweet, be detained on tongue fur without bitterness |
Through overtesting, find that the weight of principal agent and high sweetness sugars can be covered bitterness in 1:0.060 ~ 0.071, along with the increase of steviosin consumption, sugariness is excessively sweet, and simultaneously from security consideration, selecting the optimum amount scope is 1:0.060.
3, the selection of solubilizing agent
The prerequisite that absorbs in gastrointestinal tract due to medicine is to be dissolved in gastro-intestinal Fluid.Less than 0.3% the time, dissolution rate becomes the restrictive factor of whole absorption process when drug solubility.Therefore dissolution rate is also the principal element that determines its absorption.Ibuprofen belongs to insoluble drug, is the rate-limiting factor that affects principal agent absorption and even bioavailability at the gastrointestinal process in leaching, and adding solubilizing agent (sodium lauryl sulphate) in prescription is a kind of effectively short suction means.Therefore existing preparation prescription I, II, III, IV and V, solubilizing agent (sodium lauryl sulphate) consumption is respectively 0.005%, 0.01%, 0.015%, 0.025%, 0.050% of total recipe quantity, and other supplementary product kind and consumption are constant.By making sample under the Preparation Technology of Granules item, take melting as investigating index, solubilizing agent (sodium lauryl sulphate) consumption in this product prescription is screened, the results are shown in Table 2.
The melting of the prescription of the different solubilizing agent consumptions of table 2
| Prescription | Melting |
| Ⅰ | +++, suspendible is even, without foreign bodies such as breezes |
| Ⅱ | ++, suspendible is even, without foreign bodies such as breezes |
| Ⅲ | ++, suspendible is even, without foreign bodies such as breezes |
| Ⅳ | ++, suspendible is even, without foreign bodies such as breezes |
| Ⅴ | +++, suspendible is even, without foreign bodies such as breezes |
Annotate: "+" expression turbidity, "+" more multilist shows more muddy.
Through overtesting, discovery is along with the increase of sodium lauryl sulphate consumption, melting is better, but reach certain degree, melting begins again to descend, 0.010%, 0.015%, 0.025% the prescription melting that accounts for total recipe quantity is in balance period preferably, therefore the consumption of sodium lauryl sulphate is selected intermediate quantity, namely the optimum amount 0.0018(of sodium lauryl sulphate presses principal agent weight ratio 1 and calculates).
4, the investigation of stripping curve
According to the optimum prescription, by making sample under the Preparation Technology of Granules item, by the investigation to stripping curve in four kinds of dissolution mediums, purpose is to simulate gastral situation in human body.In digestive tract, the pH value of different parts sees Table 3.
The pH of different parts in table 3 digestive tract
| Each organ of digestive tract | pH |
| Stomach pH | 1.2~7.6 |
| Duodenum | 3.1~6.7 |
| Small intestinal | 5.2~6.0 |
(1) dissolution medium: the pH7.2 buffer, difference cumulative leaching rate sample time the results are shown in Table 4.
The different time cumulative leaching rate result of table 4 ibuprofen in the pH7.2 buffer
| Time (min) | 0 | 5 | 10 | 20 | 30 | 40 |
| Cumulative leaching rate (%) | 0.00 | 94.87 | 98.14 | 98.44 | 98.43 | 98.18 |
(2) dissolution medium: water, difference cumulative leaching rate sample time the results are shown in Table 5.
The different time cumulative leaching rate result of table 5 ibuprofen in water
| Time (min) | 0 | 5 | 10 | 20 | 30 | 40 |
| Cumulative leaching rate (%) | 0.00 | 45.59 | 56.90 | 70.97 | 76.28 | 84.10 |
(3) dissolution medium: the pH1.2 hydrochloric acid solution, difference cumulative leaching rate sample time the results are shown in Table 6.
The different time cumulative leaching rate result of table 6 ibuprofen in the pH1.2 hydrochloric acid solution
| Time (min) | 0 | 5 | 10 | 20 | 30 | 40 |
| Cumulative leaching rate (%) | 0.00 | 42.87 | 56.60 | 68.30 | 75.76 | 80.58 |
4) dissolution medium: the pH4.5 buffer, difference cumulative leaching rate sample time the results are shown in Table 7.
The different time cumulative leaching rate result of table 7 ibuprofen in the pH4.5 buffer
| Time (min) | 0 | 5 | 10 | 20 | 30 | 40 |
| Cumulative leaching rate (%) | 0.00 | 31.47 | 39.61 | 47.05 | 51.50 | 55.02 |
Through overtesting, find that ibuprofen 5min in medium-phosphate buffer (PH7.2) has just reached 95% left and right, reached fast the limit requirement, in other media, dissolution is also along with the increase of time increases gradually.
Stablize controlledly for the quality that proves product of the present invention, carry out following series of experiments, concrete grammar is as follows:
1. influence factor's test
According to the optimum prescription, by making sample under the Preparation Technology of Granules item, under strong illumination, high temperature, super-humid conditions, the projects such as character, moisture, related substance, dissolution and content of sample are investigated respectively.
1.1. strong illumination test
Instrument: JD-3 type illumination meter
Experimental condition: 4500lx
Sample thief is put in lighting box (self-control), regulates irradiation distance, and making intensity of illumination is 4500lx, and Continuous irradiation 10 days in the 5th day and sampling in the 10th day, is investigated the inspection of project, the results are shown in Table 8.
1.2. hot test
Instrument: DZF-6051 type vacuum drying oven
Experimental condition: 60 ℃
Sample thief is put in Constant Temp. Oven, adjusts the temperature to 60 ℃.Above-mentioned sample was placed 10 days continuously, in the 5th day and sampling in the 10th day, investigated the inspection of project, the results are shown in Table 8.
1.3. high wet test
Instrument: biochemical cultivation case
Experimental condition: relative humidity 75% (saturated NaCl solution), 92.5% (saturated KNO
3Solution)
Sample thief is placed on respectively in exsiccator, and one of them exsiccator bottom is put into saturated NaCl solution (relative humidity 75%), and saturated KNO is put in another exsiccator bottom
3Solution (relative humidity 92.5%), and then exsiccator is placed in biochemical cultivation case, adjust the temperature to 25 ℃.Above-mentioned sample was placed 10 days continuously, in the 5th day and sampling in the 10th day, investigated the inspection of project, the results are shown in Table 8.
Table 8 influence factor result of the test
Brief summary: influence factor's result of the test shows, this product was placed 5 days under high humidity (RH92.5%) condition, found that, moisture absorption weightening finish 10.6% was placed 10 days, and moisture absorption increases weight 42.9%, i.e. moisture absorption is increased weight more than 5%; Under high humidity (RH75%) condition, test with method, found that, moisture absorption is increased weight below 5%.This product was placed 10 days under high temperature (60 ℃), high humidity (RH75%), high light (4500Lx) condition, and its character, moisture, ibuprofen related substance, ibuprofen dissolution, ibuprofen and chlorphenamine maleate content all change less than significant; Zinc gluconate was placed 10 days under high temperature (60 ℃), high humidity (RH75%) condition, and its content is significant the change not; Under high light (4500Lx) condition, content 3% left and right that descended, but still meet the requirement of quality standard (draft).Therefore, determine that tentatively this product holding conditions is: sealing is preserved.
2. accelerated test
Instrument: HWS-080 type climatic chamber
Condition: 40 ℃ of relative humiditys 75% of temperature
Packing: compound membrane bag packing
Sample is placed in climatic chamber, placed 6 months.Respectively at test 1,2,3, sampling in June, investigate item inspection, the results are shown in Table 9.
Table 9 accelerated test result
Brief summary: show by the Accelerated stability test result, this product was placed 6 months under relative humidity 75% condition at 40 ℃, and indices has no significant change.
3. keep sample for a long time and investigate test
Condition: 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10%
Packing: compound membrane bag packing
Above-mentioned three batch samples are put under the room temperature natural conditions for a long time place, detect by the investigation project respectively at 3 months, 6 months, 9 months, 12 months, the results are shown in Table 10
The table 10 investigation result of the test that keeps sample for a long time
Brief summary: show by stable long-term test results, this product was placed 12 months under relative humidity 60% ± 10% condition 25 ℃ ± 2 ℃ of temperature, and indices has no significant change.
Conclusion: above result of the test shows, the quality of product of the present invention is stablized controlled.
The specific embodiment
Embodiment 1
Compound Zinc cloth granule
Prescription:
Zinc gluconate 100g
Ibuprofen 150g
Chlorphenamine maleate 2g
Sodium lauryl sulphate 0.45g
Vanillin 15g
Steviosin 15g
With sucrose to 3000g
Its preparation method is:
1) preparation of wetting agent: all dissolve with the chlorphenamine maleate of appropriate purified water with recipe quantity, standby.
2) zinc gluconate, ibuprofen, sucrose are crossed respectively 60 mesh sieves, standby.
3) take zinc gluconate, ibuprofen, sodium lauryl sulphate, steviosin, vanillin and half amount by recipe quantity
The sucrose mix homogeneously, then add the sucrose mix homogeneously of remaining half amount.
4) add wetting agent soft material processed, cross 14 mesh sieve granules processed.
5) wet granular is dried to pellet moisture in 50 ℃ ± 5 ℃ and must not crosses 4.0%, crosses 14 mesh sieve granulate.
6) granule that granulate is good adds mixing in mixer, and intermediate is sub-packed in compound membrane bag after the assay was approved, i.e. Compound Zinc cloth granule.
The present invention uses conventional equipment, and preparation technology is simple, and mouthfeel effect is good, and bioavailability is high, steady quality.Compare with ordinary preparation, this medicine is rapid-action, features good taste, be specially adapted to children's with, have good toleration characteristics, so therapeutic scheme will be easy.
Although the present invention describes with reference to specific embodiment, this description and not meaning that is construed as limiting the present invention.With reference to description of the invention, other distortion of the disclosed embodiments all can be expected for those skilled in the art.Therefore, claim restricted portion and spirit under such distortion can not break away from.
Claims (8)
1. Compound Zinc cloth Orally administered composition is characterized in that containing following component level weight ratio:
Principal agent: 1
High sweetness sugars: 0.036 ~ 0.083
Filler: 5 ~ 15
Surfactant: 0.0006 ~ 0.0060
Wherein: high sweetness sugars is selected from acesulfame potassium, steviosin, cyclamate, saccharin sodium, sucralose, aspartame;
Filler is selected from microcrystalline Cellulose, sucrose, lactose, mannitol, starch;
Surfactant is selected from sodium lauryl sulphate, tween 80, Arlacel-80.
2. the preparation of claim 1 is characterized in that containing following component level weight ratio:
Principal agent: 1
High sweetness sugars: 0.048 ~ 0.071
Filler: 10 ~ 15
Surfactant: 0.0012 ~ 0.0030
Wherein: high sweetness sugars is selected from acesulfame potassium, steviosin, cyclamate, saccharin sodium, sucralose, aspartame;
Filler is selected from microcrystalline Cellulose, sucrose, lactose, mannitol, starch;
Surfactant is selected from sodium lauryl sulphate, tween 80, Arlacel-80.
3. the preparation of claim 1 is characterized in that containing following component level weight ratio:
Principal agent: 1
High sweetness sugars: 0.060
Filler: 10.78
Surfactant: 0.0018
Wherein: high sweetness sugars is selected from acesulfame potassium, steviosin, cyclamate, saccharin sodium, sucralose, aspartame;
Filler is selected from microcrystalline Cellulose, sucrose, lactose, mannitol, starch;
Surfactant is selected from sodium lauryl sulphate, tween 80, Arlacel-80.
Claim 1 to any one preparation of claim 3, it is characterized in that the preferred steviosin of high sweetness sugars wherein; Filler is sucrose; The surfactant preferably sodium dodecyl sulfate.
5. the Orally administered composition of claim 1 any one to the claim 4, its dosage form is granule.
6. claim 1 to any one preparation of claim 3, also contains essence.
7. claim 1 to the Orally administered composition of claim 6, when dosage form is granule, is characterized in that, formula consists of:
Zinc gluconate 100g
Ibuprofen 150g
Chlorphenamine maleate 2g
Sodium lauryl sulphate 0.45g
Vanillin 15g
Steviosin 15g
With sucrose to 3000g
8. claim 1 to the preparation method of the Orally administered composition of claim 7, is characterized in that, method is as follows:
1) preparation of wetting agent: all dissolve with the chlorphenamine maleate of appropriate purified water with recipe quantity, standby;
2) zinc gluconate, ibuprofen, sucrose are crossed respectively 60 mesh sieves, standby;
3) take zinc gluconate, ibuprofen, sodium lauryl sulphate, steviosin, vanillin and half amount by recipe quantity
The sucrose mix homogeneously, then add the sucrose mix homogeneously of remaining half amount;
4) add wetting agent soft material processed, cross 14 mesh sieve granules processed;
5) wet granular is dried to pellet moisture in 50 ℃ ± 5 ℃ and must not crosses 4.0%, crosses 14 mesh sieve granulate;
6) granule that granulate is good adds mixing in mixer, and intermediate is sub-packed in compound membrane bag after the assay was approved, i.e. Compound Zinc cloth granule.
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|---|---|---|---|
| CN2011103604442A CN103099807A (en) | 2011-11-15 | 2011-11-15 | Compound zinc gluconate and ibuprofen oral-administration composition for covering bitter taste and improving ibuprofen dissolution |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104042596A (en) * | 2014-06-25 | 2014-09-17 | 哈尔滨华瑞生化药业有限责任公司 | Ibuprofen granule and preparation method thereof |
| CN112972399A (en) * | 2021-03-03 | 2021-06-18 | 天津大学 | Ibuprofen-loaded o-vanillin composite particle and preparation method thereof |
| CN116420874A (en) * | 2023-04-26 | 2023-07-14 | 仙乐健康科技股份有限公司 | A composition without bitter taste and product comprising the same |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1091638A (en) * | 1993-02-27 | 1994-09-07 | 大同市星火制药厂 | Anti-flu new drug---Xinkekang (zinc cloth granule) |
| CN1100306A (en) * | 1994-05-30 | 1995-03-22 | 吴秀清 | Compound zinc gluconate capsules, tablets and buccal tablets and their preparing method |
| CN102038700A (en) * | 2009-10-14 | 2011-05-04 | 海南澳美华制药有限公司 | Bitter-taste-masking erythromycin-cydocarbonate-containing oral composition |
| CN102188445A (en) * | 2010-03-12 | 2011-09-21 | 上海延安药业有限公司 | Compound preparation of aminophylline, and preparation method thereof |
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2011
- 2011-11-15 CN CN2011103604442A patent/CN103099807A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1091638A (en) * | 1993-02-27 | 1994-09-07 | 大同市星火制药厂 | Anti-flu new drug---Xinkekang (zinc cloth granule) |
| CN1100306A (en) * | 1994-05-30 | 1995-03-22 | 吴秀清 | Compound zinc gluconate capsules, tablets and buccal tablets and their preparing method |
| CN102038700A (en) * | 2009-10-14 | 2011-05-04 | 海南澳美华制药有限公司 | Bitter-taste-masking erythromycin-cydocarbonate-containing oral composition |
| CN102188445A (en) * | 2010-03-12 | 2011-09-21 | 上海延安药业有限公司 | Compound preparation of aminophylline, and preparation method thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104042596A (en) * | 2014-06-25 | 2014-09-17 | 哈尔滨华瑞生化药业有限责任公司 | Ibuprofen granule and preparation method thereof |
| CN104042596B (en) * | 2014-06-25 | 2017-01-04 | 哈尔滨华瑞生化药业有限责任公司 | A kind of ibuprofen granule and preparation method thereof |
| CN112972399A (en) * | 2021-03-03 | 2021-06-18 | 天津大学 | Ibuprofen-loaded o-vanillin composite particle and preparation method thereof |
| CN116420874A (en) * | 2023-04-26 | 2023-07-14 | 仙乐健康科技股份有限公司 | A composition without bitter taste and product comprising the same |
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Application publication date: 20130515 |