CN102488689B - Compound zinc gluconateand ibuprofen granule capable of curing cold and preparation method thereof - Google Patents
Compound zinc gluconateand ibuprofen granule capable of curing cold and preparation method thereof Download PDFInfo
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- CN102488689B CN102488689B CN 201110410726 CN201110410726A CN102488689B CN 102488689 B CN102488689 B CN 102488689B CN 201110410726 CN201110410726 CN 201110410726 CN 201110410726 A CN201110410726 A CN 201110410726A CN 102488689 B CN102488689 B CN 102488689B
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- ibuprofen
- zinc
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- 239000008187 granular material Substances 0.000 title claims abstract description 78
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 title claims abstract description 70
- 229960001680 ibuprofen Drugs 0.000 title claims abstract description 65
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 title claims abstract description 58
- 239000011701 zinc Substances 0.000 title claims abstract description 58
- 229910052725 zinc Inorganic materials 0.000 title claims abstract description 58
- 238000002360 preparation method Methods 0.000 title claims abstract description 48
- 150000001875 compounds Chemical class 0.000 title claims abstract description 42
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 claims abstract description 41
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 37
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000003085 diluting agent Substances 0.000 claims abstract description 12
- 239000004744 fabric Substances 0.000 claims description 49
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 claims description 39
- 229960000306 zinc gluconate Drugs 0.000 claims description 39
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 19
- 229930006000 Sucrose Natural products 0.000 claims description 19
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 19
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 19
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 19
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 19
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 11
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- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 4
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 4
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- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
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- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 description 2
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 2
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention belongs to the technical field of medicinal preparation and relates to a compound zinc gluconateand ibuprofen granule capable of curing the cold and a preparation method thereof. The compound zinc gluconateand ibuprofen granule is composed of brufen cyclodextrin clathrate compound, gluconic acid zinc, chlorpheniramine, diluents and adhesives, wherein dosage molar ratio of brufen and cyclodextrin in the brufen cyclodextrin clathrate compound is 1:1 to 1:2, weight ratio of the brufen, gluconic acid zinc and chlorpheniramine is 1:(0.4-0.8):(0.01-0.03), dosage of the diluents is 15% to 40% of the whole weight of the compound zinc gluconateand ibuprofen granule, and dosage of the adhesives is 2% to 6% of the whole weight of the compound zinc gluconateand ibuprofen granule. The compound zinc gluconateand ibuprofen granule is good in taste, simultaneously resolves the problem that brufen blood concentration is large in fluctuation after patients take the compound zinc gluconateand ibuprofen granule, and effectively reduces side effects.
Description
Technical field
The invention belongs to technical field of medicine, relate to a kind of Compound Zinc cloth granule for the treatment of flu and preparation method thereof, Compound Zinc cloth granule that particularly the ibuprofen blood concentration fluctuation is less, side effect is little in a kind of rear patient's body of taking medicine and preparation method thereof.
Background technology
Ibuprofen (Ibuprofen) is one of the most successful ntipyretic analgesic medicine of development in recent years, and China has classified ibuprofen as the pillar product of realizing that the antipyretic analgesic breed structure upgrades.It except antiinflammatory action, again tool ease pain significantly, antipyretic effect and good safety; Its antiinflammation is than the large 16-32 of aspirin times, and large 20 times of refrigeration function, the large 16-32 of analgesic activity are doubly; The effect of bringing down a fever is than the principal item in the antipyretic analgesic---and aspirin, acetaminophen are fast and lasting.The patient takes behind this medicine often by the untoward reaction of symptom of digestive tract, comprises dyspepsia, stomach burn feeling, stomachache, feels sick, vomiting.Zinc gluconate (Zinc Gluconate) is separated into zinc ion and gluconic acid in vivo, participates in synthetic and multiple Enzyme Production and the activation of ribonucleic acid and DNA (deoxyribonucleic acid), and the effect that strengthens cytophagous phagocytic activity is arranged.Current research shows that zinc ion all has obvious curative effect at aspects such as preventing cold virus breeding, shortening flu pathogenic process.Chlorphenamine maleate (Chlorphenamine Maleate) is antihistaminic, has competitive blocking histamine H1 receptor and to antfhistamine effect, it also has the effect of anti-M cholinoceptor, reduce the nasal mucosa secretion, can obviously eliminate the watery nasal discharge, sneeze, the nasal congestion that are caused by flu, shed tears and throat's allergic symptom such as itch.
Ibuprofen, zinc gluconate and chlorphenamine maleate use in conjunction have significant synergism when treatment common cold or influenza, be a comprehensive compound medicine of therapeutic effect.For the compound preparation of these three medicines, gone on the market or bibliographical information arranged Compound Zinc cloth granule, zinc cloth sheet (conventional tablet), Luo Fen Portugal zinc that quick dispersible tablet and compound soft capsule preparation arranged.Yet, because the Half-life in vivo of ibuprofen is 1.8-2 hour, the adult need take 150 milligrams at every turn, take every day 3 times, cause the dosage of ibuprofen in the existing Compound Zinc granule large, and the ibuprofen in the preparation discharges too fast in human body, causes blood concentration fluctuation larger, has brought comparatively serious dyspepsia, stomach burn feeling, stomachache, feels sick, the side effect such as vomiting.Therefore, need the Compound Zinc cloth preparation that the ibuprofen blood concentration fluctuation is less, side effect is little in a kind of rear patient's body of taking medicine of invention.
Summary of the invention
The purpose of this invention is to provide a kind of Compound Zinc cloth granule for the treatment of flu.
Another object of the present invention provides the preparation method of the Compound Zinc cloth granule for the treatment of flu.
The present invention is achieved through the following technical solutions.
One, a kind of Compound Zinc cloth granule for the treatment of flu, a kind of Compound Zinc cloth granule for the treatment of flu, it is characterized in that: formed by ibuprofen cyclodextrin clathrate, zinc gluconate, chlorphenamine maleate, diluent and binding agent, the consumption mol ratio of ibuprofen and cyclodextrin is 1:1～1:2 in the wherein said ibuprofen cyclodextrin clathrate, the weight ratio of ibuprofen, zinc gluconate and chlorphenamine maleate is 1:0.4-0.8:0.01-0.03, the diluent consumption accounts for 15%～40% of granule gross weight, and binder dosage accounts for 2%～6% of granule gross weight.
Described cyclodextrin is beta-schardinger dextrin-.
Further, the weight ratio of described ibuprofen, zinc gluconate and chlorphenamine maleate is 1:0.5:0.01.
Described diluent is selected from one or more of microcrystalline Cellulose, micropowder silica gel, Icing Sugar and sucrose.
Described binding agent is selected from hydroxypropyl cellulose or/and sodium carboxymethyl cellulose.
Two, the preparation method of the Compound Zinc cloth granule for the treatment of flu of the present invention comprises the steps:
(1) with 50 ℃ of ibuprofen, zinc gluconate, chlorphenamine maleate, beta-schardinger dextrin-, diluent and binding agents dry 3 hours respectively, it was for subsequent use to cross 100 mesh sieves;
(2) beta-schardinger dextrin-is added water, under 45 ~ 60 ℃ temperature conditions, stir under the rotating speed of 750r/min ~ 3000r/min and make saturated aqueous solution;
(3) ibuprofen being dissolved in weight ratio is 50% acetonitrile solution, and then the speed with 1 ~ 3mL/min is added drop-wise in the saturated beta-schardinger dextrin-aqueous solution of above-mentioned preparation, and continuation was stirred 3 hours after finishing, and spray drying makes cyclodextrin clathrate;
(4) described cyclodextrin clathrate is crossed 100 mesh sieves, then with zinc gluconate, chlorphenamine maleate, diluent, binding agent mix homogeneously after soft material processed, cross 20 mesh sieves wet granular processed, 45 ~ 60 ℃ of wet granulars is fully dry, cross 20 mesh sieve granulate and obtain Compound Zinc cloth granule.
Compared with prior art, the present invention has following advantage and marked improvement:
1, overcome the problem that ibuprofen can't steadily discharge in the Compound Zinc cloth granule of prior art.Compound Zinc cloth granule of the present invention in vivo can be fast, steadily discharge, take effect immediately after on the one hand the patient being taken medicine, reduced on the other hand medicine to the gastrointestinal zest, and can keep relatively constant drug level, reduce potential toxic and side effects, prolonged the action time of medicine.Stripping feature by embodiment 4 is investigated result of the test and can be found out, zinc cloth granule of the present invention and plain particles in 30min the time accumulation dissolution meet the stripping requirement of granule all greater than 80%.Yet comparative example's granule is too fast at front 15min rate of release, fluctuating widely of drug level occur easily in patient body, causes untoward reaction.And the zinc cloth granule of the present invention's preparation discharges steadily, can effectively avoid the peak valley phenomenon of medicine, reduces the untoward reaction that causes because blood drug level is too high.
2, overcome the problem of the zinc cloth granule heavy bitter taste of prior art.Can cover well the bitterness of ibuprofen by the zinc cloth granule of cyclodextrin inclusion compound, the compliance, particularly old man, child etc. that have increased patient's medication are swallowed inconvenient patient.
Description of drawings
Figure
1It is ibuprofen accumulation dissolution curve chart in the zinc cloth granule of embodiment 1 preparation.
Fig. 2 is ibuprofen accumulation dissolution curve chart in the zinc cloth granule of embodiment 2 preparation.
Fig. 3 is ibuprofen accumulation dissolution curve chart in the zinc cloth granule of embodiment 3 preparation.
Fig. 4 is ibuprofen accumulation dissolution curve chart in the zinc cloth granule of comparative example 1 preparation.
The specific embodiment
Below be the specific embodiment of the Compound Zinc cloth granule that the present invention relates to, technical scheme of the present invention is done further the description, but protection scope of the present invention be not limited to these embodiment.Every do not deviate from the change of the present invention design or be equal to substitute include within protection scope of the present invention.
The preparation of embodiment 1 zinc cloth granule
Prescription:
| The supplementary material title | Consumption |
| Ibuprofen | 200g（1.0mol） |
| Beta-schardinger dextrin- | 2000g（1.8.mol） |
| Zinc gluconate | 100g |
| Chlorphenamine maleate | 2g |
| Microcrystalline Cellulose | 450g |
| Sodium carboxymethyl cellulose | 75g |
| Purified water | In right amount |
| Make 1000 bags |
Preparation technology:
(1) with 50 ℃ of ibuprofen, zinc gluconate, chlorphenamine maleate, beta-schardinger dextrin-, microcrystalline Cellulose and sodium carboxymethyl cellulose dry 3 hours respectively, it was for subsequent use to cross 100 mesh sieves.
(2) beta-schardinger dextrin-is added water, under 45 ℃ temperature conditions, stir under the rotating speed of 750r/min with homogenizer and to make saturated aqueous solution.
(3) ibuprofen being dissolved in weight ratio is 50% acetonitrile solution, and then the speed with 3mL/min is added drop-wise in the saturated beta-schardinger dextrin-aqueous solution of above-mentioned preparation, and continuation was stirred 3 hours after finishing, and spray drying makes cyclodextrin clathrate.
(4) described cyclodextrin clathrate is crossed 100 mesh sieves, then with zinc gluconate, chlorphenamine maleate, microcrystalline Cellulose and sodium carboxymethyl cellulose mix homogeneously after soft material processed, cross 20 mesh sieves wet granular processed, 45 ℃ of wet granulars is fully dry, cross 20 mesh sieve granulate and obtain Compound Zinc cloth granule.
The preparation of embodiment 2 zinc cloth granules
Prescription:
| The supplementary material title | Consumption |
| Ibuprofen | 200g（1.0mol） |
| Beta-schardinger dextrin- | 1500g（1.3mol） |
| Zinc gluconate | 150g |
| Chlorphenamine maleate | 4g |
| Microcrystalline Cellulose | 200g |
| Sucrose | 350g |
| Sodium carboxymethyl cellulose | 80g |
| Purified water | In right amount |
| Make 1000 bags |
Preparation technology:
(1) with 50 ℃ of ibuprofen, zinc gluconate, chlorphenamine maleate, beta-schardinger dextrin-, microcrystalline Cellulose, sucrose and sodium carboxymethyl cellulose dry 3 hours respectively, it was for subsequent use to cross 100 mesh sieves.
(2) beta-schardinger dextrin-is added water, under 60 ℃ temperature conditions, stir under the rotating speed of 3000r/min with homogenizer and to make saturated aqueous solution.
(3) ibuprofen being dissolved in weight ratio is 50% acetonitrile solution, and then the speed with 2mL/min is added drop-wise in the saturated beta-schardinger dextrin-aqueous solution of above-mentioned preparation, and continuation was stirred 3 hours after finishing, and spray drying makes cyclodextrin clathrate.
(4) described cyclodextrin clathrate is crossed 100 mesh sieves, then with zinc gluconate, chlorphenamine maleate, microcrystalline Cellulose, sucrose and sodium carboxymethyl cellulose mix homogeneously after soft material processed, cross 20 mesh sieves wet granular processed, 60 ℃ of wet granulars is fully dry, cross 20 mesh sieve granulate and obtain Compound Zinc cloth granule.
The preparation of embodiment 3 zinc cloth granules
Prescription:
| The supplementary material title | Consumption |
| Ibuprofen | 200g（1.0mol） |
| Beta-schardinger dextrin- | 1700g（1.5mol） |
| Zinc gluconate | 100g |
| Chlorphenamine maleate | 2g |
| Microcrystalline Cellulose | 250g |
| Sucrose | 250g |
| Micropowder silica gel | 180g |
| Sodium carboxymethyl cellulose | 100g |
| Purified water | In right amount |
| Make altogether 1000 bags |
Preparation technology:
(1) with 50 ℃ of ibuprofen, zinc gluconate, chlorphenamine maleate, beta-schardinger dextrin-, microcrystalline Cellulose, sucrose, micropowder silica gel and sodium carboxymethyl cellulose dry 3 hours respectively, it was for subsequent use to cross 100 mesh sieves.
(2) beta-schardinger dextrin-is added water, under 50 ℃ temperature conditions, stir under the rotating speed of 1800r/min with homogenizer and to make saturated aqueous solution.
(3) ibuprofen being dissolved in weight ratio is 50% acetonitrile solution, and then the speed with 3mL/min is added drop-wise in the saturated beta-schardinger dextrin-aqueous solution of above-mentioned preparation, and continuation was stirred 3 hours after finishing, and spray drying makes cyclodextrin clathrate.
(4) described cyclodextrin clathrate is crossed 100 mesh sieves, then with zinc gluconate, chlorphenamine maleate, microcrystalline Cellulose, sucrose, micropowder silica gel and sodium carboxymethyl cellulose mix homogeneously after soft material processed, cross 20 mesh sieves wet granular processed, 50 ℃ of wet granulars is fully dry, cross 20 mesh sieve granulate and obtain Compound Zinc cloth granule.
The preparation of embodiment 4 zinc cloth granules
Prescription:
| The supplementary material title | Consumption |
| Ibuprofen | 200g（1.0mol） |
| Beta-schardinger dextrin- | 1700g（1.5mol） |
| Zinc gluconate | 100g |
| Chlorphenamine maleate | 2g |
| Sucrose | 680g |
| Sodium carboxymethyl cellulose | 100g |
| Purified water | In right amount |
| Make altogether 1000 bags |
Preparation technology:
(1) with 50 ℃ of ibuprofen, zinc gluconate, chlorphenamine maleate, beta-schardinger dextrin-, sucrose and sodium carboxymethyl cellulose dry 3 hours respectively, it was for subsequent use to cross 100 mesh sieves.
(2) beta-schardinger dextrin-is added water, under 50 ℃ temperature conditions, stir under the rotating speed of 1800r/min with homogenizer and to make saturated aqueous solution.
(3) ibuprofen being dissolved in weight ratio is 50% acetonitrile solution, and then the speed with 1mL/min is added drop-wise in the saturated beta-schardinger dextrin-aqueous solution of above-mentioned preparation, and continuation was stirred 3 hours after finishing, and spray drying makes cyclodextrin clathrate.
(4) described cyclodextrin clathrate is crossed 100 mesh sieves, then with zinc gluconate, chlorphenamine maleate, sucrose and sodium carboxymethyl cellulose mix homogeneously after soft material processed, cross 20 mesh sieves wet granular processed, 50 ℃ of wet granulars is fully dry, cross 20 mesh sieve granulate and obtain Compound Zinc cloth granule.
The preparation of embodiment 5 zinc cloth granules
Prescription:
| The supplementary material title | Consumption |
| Ibuprofen | 200g（1.0mol） |
| Beta-schardinger dextrin- | 1100g（1.0mol） |
| Zinc gluconate | 160g |
| Chlorphenamine maleate | 6g |
| Sucrose | 520g |
| Micropowder silica gel | 520g |
| Sodium carboxymethyl cellulose | 78g |
| Hydroxypropyl cellulose | 78g |
| Purified water | In right amount |
| Make altogether 1000 bags |
Preparation technology:
(1) with 50 ℃ of ibuprofen, zinc gluconate, chlorphenamine maleate, beta-schardinger dextrin-, sucrose, micropowder silica gel, sodium carboxymethyl cellulose and hydroxypropyl celluloses dry 3 hours respectively, it was for subsequent use to cross 100 mesh sieves.
(2) beta-schardinger dextrin-is added water, under 50 ℃ temperature conditions, stir under the rotating speed of 2000r/min with homogenizer and to make saturated aqueous solution.
(3) ibuprofen being dissolved in weight ratio is 50% acetonitrile solution, and then the speed with 3mL/min is added drop-wise in the saturated beta-schardinger dextrin-aqueous solution of above-mentioned preparation, and continuation was stirred 3 hours after finishing, and spray drying makes cyclodextrin clathrate.
(4) described cyclodextrin clathrate is crossed 100 mesh sieves, then with zinc gluconate, chlorphenamine maleate, sucrose, micropowder silica gel, sodium carboxymethyl cellulose and hydroxypropyl cellulose mix homogeneously after soft material processed, cross 20 mesh sieves wet granular processed, 50 ℃ of wet granulars is fully dry, cross 20 mesh sieve granulate and obtain Compound Zinc cloth granule.
The preparation of embodiment 6 zinc cloth granules
Prescription:
| The supplementary material title | Consumption |
| Ibuprofen | 200g（1.0mol） |
| Gamma-cyclodextrin | 1300g（1.0mol） |
| Zinc gluconate | 160g |
| Chlorphenamine maleate | 6g |
| Micropowder silica gel | 945g |
| Hydroxypropyl cellulose | 89g |
| Purified water | In right amount |
| Make altogether 1000 bags |
Preparation technology:
(1) with 50 ℃ of ibuprofen, zinc gluconate, chlorphenamine maleate, gamma-cyclodextrin, micropowder silica gel and hydroxypropyl celluloses dry 3 hours respectively, it was for subsequent use to cross 100 mesh sieves.
(2) gamma-cyclodextrin is added water, under 50 ℃ temperature conditions, stir under the rotating speed of 2000r/min with homogenizer and to make saturated aqueous solution.
(3) ibuprofen being dissolved in weight ratio is 50% acetonitrile solution, and then the speed with 3mL/min is added drop-wise in the saturated gamma-cyclodextrin aqueous solution of above-mentioned preparation, and continuation was stirred 3 hours after finishing, and spray drying makes cyclodextrin clathrate.
(4) described cyclodextrin clathrate is crossed 100 mesh sieves, then with zinc gluconate, chlorphenamine maleate, micropowder silica gel and hydroxypropyl cellulose mix homogeneously after soft material processed, cross 20 mesh sieves wet granular processed, 50 ℃ of wet granulars is fully dry, cross 20 mesh sieve granulate and obtain Compound Zinc cloth granule.
The preparation of embodiment 7 zinc cloth granules
Prescription:
| The supplementary material title | Consumption |
| Ibuprofen | 200g（1.0mol） |
| Beta-schardinger dextrin- | 2200g（2.0mol） |
| Zinc gluconate | 80g |
| Chlorphenamine maleate | 6g |
| Icing Sugar | 435g |
| Hydroxypropyl cellulose | 60g |
| Purified water | In right amount |
| Make altogether 1000 bags |
Preparation technology:
(1) with 50 ℃ of ibuprofen, zinc gluconate, chlorphenamine maleate, beta-schardinger dextrin-, Icing Sugar and hydroxypropyl celluloses dry 3 hours respectively, it was for subsequent use to cross 100 mesh sieves.
(2) beta-schardinger dextrin-is added water, under 50 ℃ temperature conditions, stir under the rotating speed of 1500r/min with homogenizer and to make saturated aqueous solution.
(3) ibuprofen being dissolved in weight ratio is 50% acetonitrile solution, and then the speed with 2mL/min is added drop-wise in the saturated beta-schardinger dextrin-aqueous solution of above-mentioned preparation, and continuation was stirred 3 hours after finishing, and spray drying makes cyclodextrin clathrate.
(4) described cyclodextrin clathrate is crossed 100 mesh sieves, then with zinc gluconate, chlorphenamine maleate, Icing Sugar and hydroxypropyl cellulose mix homogeneously after soft material processed, cross 20 mesh sieves wet granular processed, 50 ℃ of wet granulars is fully dry, cross 20 mesh sieve granulate and obtain Compound Zinc cloth granule.
The preparation of embodiment 8 zinc cloth granules
Prescription:
| The supplementary material title | Consumption |
| Ibuprofen | 200g（1.0mol） |
| Alpha-cyclodextrin | 2000g（2.0mol） |
| Zinc gluconate | 80g |
| Chlorphenamine maleate | 6g |
| Icing Sugar | 220g |
| Sucrose | 200g |
| Hydroxypropyl cellulose | 94g |
| Purified water | In right amount |
| Make altogether 1000 bags |
Preparation technology:
(1) with 50 ℃ of ibuprofen, zinc gluconate, chlorphenamine maleate, alpha-cyclodextrin, Icing Sugar, sucrose and hydroxypropyl celluloses dry 3 hours respectively, it was for subsequent use to cross 100 mesh sieves.
(2) alpha-cyclodextrin is added water, under 50 ℃ temperature conditions, stir under the rotating speed of 1500r/min with homogenizer and to make saturated aqueous solution.
(3) ibuprofen being dissolved in weight ratio is 50% acetonitrile solution, and then the speed with 3mL/min is added drop-wise in the saturated alpha-cyclodextrin aqueous solution of above-mentioned preparation, and continuation was stirred 3 hours after finishing, and spray drying makes cyclodextrin clathrate.
(4) described cyclodextrin clathrate is crossed 100 mesh sieves, then with zinc gluconate, chlorphenamine maleate, Icing Sugar, sucrose and hydroxypropyl cellulose mix homogeneously after soft material processed, cross 20 mesh sieves wet granular processed, 50 ℃ of wet granulars is fully dry, cross 20 mesh sieve granulate and obtain Compound Zinc cloth granule.
The comparative example 1
Prescription:
| The supplementary material title | Consumption |
| Ibuprofen | 150g |
| Zinc gluconate | 100g |
| Chlorphenamine maleate | 2g |
| Sodium carboxymethyl cellulose | 90g |
| Stevioside | 15g |
| The orange juice powdered flavor | 15g |
| Sodium lauryl sulphate | 0.4g |
| Sucrose | 2600g |
| Make altogether 1000 bags |
Preparation technology:
(1) chlorphenamine maleate is dissolved in the purified water, stirs, make wetting agent.
(2) zinc gluconate, stevioside, sodium carboxymethyl cellulose, sodium lauryl sulphate, cane sugar powder are added efficient wet granulator together; stir the cutting knife low or first gear and be dry mixed 180 seconds; open the granulation cutting knife, add wetting agent from addition funnel gradually, discharging after continuing to granulate 150 seconds.
(3) after the discharging by 16 orders wet granular processed, 80 ℃ ± 5 ℃ constant pressure and dries 140 minutes, then 16 order granulate.
(4) the dried granule behind the granulate is mixed with ibuprofen, orange juice powdered flavor, and get final product.
The stripping feature of embodiment 9 zinc cloth granules of the present invention is investigated
Adopt dissolution method (two appendix XC the second methods of Chinese Pharmacopoeia version in 2005), enter in the sedimentation basket zinc cloth granule one is packed, take water as solvent, rotating speed is 50r/min, and temperature is 37 ± 2 ℃ of in accordance with the law operations, respectively 5,10,15,20,25, during 30min, taking liquid 5mL, replenish simultaneously the water of equivalent, medicinal liquid is crossed the membrane filtration of 0.45 μ m, measure with high performance liquid chromatography.Among the figure, abscissa express time, vertical coordinate represent to accumulate dissolution.
The plain particles of the zinc cloth granule among the embodiment 1 ~ 3 and comparative example's 1 preparation is carried out the stripping feature as stated above investigate, its stripping curve is seen respectively Fig. 1 ~ 4.We can find out from figure, and zinc cloth granule of the present invention and plain particles time accumulation dissolution in 30min meets the stripping requirement of granule all greater than 80%.Yet comparative example 1 granule is too fast at front 15min rate of release, fluctuating widely of drug level occur easily in patient body, causes untoward reaction.And the granule of the present invention's preparation discharges steadily, can effectively avoid the peak valley phenomenon of medicine, reduces the untoward reaction that causes because blood drug level is too high.
Claims (5)
1. Compound Zinc cloth granule for the treatment of flu, it is characterized in that: formed by ibuprofen cyclodextrin clathrate, zinc gluconate, chlorphenamine maleate, diluent and binding agent, the consumption mol ratio of ibuprofen and cyclodextrin is 1:1～1:2 in the wherein said ibuprofen cyclodextrin clathrate, the weight ratio of ibuprofen, zinc gluconate and chlorphenamine maleate is 1:0.4-0.8:0.01-0.03, the diluent consumption accounts for 15%～40% of granule gross weight, and binder dosage accounts for 2%～6% of granule gross weight; Described cyclodextrin is beta-schardinger dextrin-;
Described ibuprofen cyclodextrin clathrate is prepared from as follows: with 50 ℃ of dryings of ibuprofen 3 hours, it was for subsequent use to cross 100 mesh sieves; Beta-schardinger dextrin-is added water, under 45 ~ 60 ℃ temperature conditions, stir under the rotating speed of 750r/min ~ 3000r/min and make saturated aqueous solution; It is 50% acetonitrile solution that ibuprofen is dissolved in weight ratio, and then the speed with 1-3ml/min is added drop-wise in the saturated beta-schardinger dextrin-aqueous solution of above-mentioned preparation, and continuation was stirred 3 hours after finishing, and spray drying makes cyclodextrin clathrate.
2. according to claim 1 described a kind of Compound Zinc cloth granule for the treatment of flu, it is characterized in that: the weight ratio of described ibuprofen, zinc gluconate and chlorphenamine maleate is 1:0.5:0.01.
3. according to claim 1 described a kind of Compound Zinc cloth granule for the treatment of flu, it is characterized in that: described diluent is selected from one or more of microcrystalline Cellulose, micropowder silica gel, Icing Sugar and sucrose.
4. according to claim 1 described a kind of Compound Zinc cloth granule for the treatment of flu, it is characterized in that: described binding agent is selected from hydroxypropyl cellulose or/and sodium carboxymethyl cellulose.
5. the preparation method of the Compound Zinc cloth granule for the treatment of flu claimed in claim 1 is characterized in that: comprise the steps:
(1) with 50 ℃ of ibuprofen, zinc gluconate, chlorphenamine maleate, beta-schardinger dextrin-, diluent and binding agents dry 3 hours respectively, it was for subsequent use to cross 100 mesh sieves;
(2) beta-schardinger dextrin-is added water, under 45 ~ 60 ℃ temperature conditions, stir under the rotating speed of 750r/min ~ 3000r/min and make saturated aqueous solution;
(3) ibuprofen being dissolved in weight ratio is 50% acetonitrile solution, and then the speed with 1 ~ 3mL/min is added drop-wise in the saturated beta-schardinger dextrin-aqueous solution of above-mentioned preparation, and continuation was stirred 3 hours after finishing, and spray drying makes cyclodextrin clathrate;
(4) described cyclodextrin clathrate is crossed 100 mesh sieves, then with zinc gluconate, chlorphenamine maleate, diluent, binding agent mix homogeneously after soft material processed, cross 20 mesh sieves wet granular processed, 45 ~ 60 ℃ of wet granulars is fully dry, cross 20 mesh sieve granulate and obtain Compound Zinc cloth granule.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110410726 CN102488689B (en) | 2011-12-12 | 2011-12-12 | Compound zinc gluconateand ibuprofen granule capable of curing cold and preparation method thereof |
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| CN103432125B (en) * | 2013-09-10 | 2015-04-01 | 北京首儿药厂 | Preparation method of compound zinc gluconate and ibuprofen granules |
| CN110664810A (en) * | 2019-11-12 | 2020-01-10 | 南京臣功制药股份有限公司 | Compound zinc-coated granules and preparation method thereof |
Citations (2)
| 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) |
| CN1098288A (en) * | 1993-07-31 | 1995-02-08 | 史密丝克莱恩比彻姆有限公司 | Pharmaceutical composition |
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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) |
| CN1098288A (en) * | 1993-07-31 | 1995-02-08 | 史密丝克莱恩比彻姆有限公司 | Pharmaceutical composition |
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