CN103284966A - Candesartan cilexetil dispersible tablet - Google Patents
Candesartan cilexetil dispersible tablet Download PDFInfo
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- CN103284966A CN103284966A CN2013101317298A CN201310131729A CN103284966A CN 103284966 A CN103284966 A CN 103284966A CN 2013101317298 A CN2013101317298 A CN 2013101317298A CN 201310131729 A CN201310131729 A CN 201310131729A CN 103284966 A CN103284966 A CN 103284966A
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- candesartan cilexetil
- dispersible tablet
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Abstract
The invention relates to a candesartan cilexetil dispersible tablet. The dispersing tablet is characterized by comprising candesartan cilexetil, one or more accessory materials selected from the group consisting of 1 to 20% of polyvinylpolypyrrolidone (PVPP), sodium carboxymethyl starch and sodium carboxymethylcellulose and 1 to 20% of low-substituted hydroxy propyl cellulose (L-HPC), wherein the weight percentage of the above-mentioned components is calculated on the basis of the gross weight of the dispersing tablet. Preferably, the candesartan cilexetil dispersible tablet further comprises microcrystalline cellulose. The candesartan cilexetil dispersible tablet provided by the invention has the advantages of rapid disintegration and dispersion, a fast dissolution rate and high bioavailability.
Description
Technical field
The present invention relates to a kind of candesartan Cilexetil dispersible tablet and preparation method thereof, belong to medical technical field.
Background technology
Candesartan Cilexetil is a kind of novel angiotensin ii receptor antagonist, has caused in resisting hypertension market widely to pay close attention to.The effect of this drug selectivity ground blocking-up AngII in circulation and tissue, antihypertensive effect is remarkable.Its structural formula is as follows:
Candesartan Cilexetil is white or off-white color crystalline powder; Easily molten in chloroform, in acetone, dissolve, slightly molten in methanol, slightly soluble in ethanol, almost insoluble in water.
Dispersible tablet (dispersible tablets) mean meet water rapidly disintegrate form the tablet of even aqueous dispersion, be to be a kind of novel form that solves that the solid preparation disintegrate is slow, stripping is poor, bioavailability is not high or problems such as liquid preparation poor stability, packing, transportation, storage inconvenience are developed.The dispersible tablet taking convenience is taken after can disperseing in water, or is swallowed, chews clothes, is fit to old man, child or dysphagia patients and takes.Except having the ordinary tablet good stability, be easy to carry, outside the advantage such as taking convenience, also have the bioavailability advantage of higher.Mainly be applicable to insoluble drug and the medicine that the bioavailability problem is arranged.
Quick-release tablets such as dispersible tablet and oral cavity disintegration tablet, effervescent tablet are different.Do not need water when oral cavity disintegration tablet is taken, in 30 seconds disintegrate complete, but preparation technology is complicated, the need that have adopt technologies such as lyophilization, cost height.Effervescent tablet must use effervescent and water soluble adjuvant, and technical process is high to temperature, humidity requirement.And dispersible tablet gets final product by general film-making prepared.
Be insoluble in water, problem that bioavailability is low in order to solve candesartan Cilexetil, attempt candesartan Cilexetil is made dispersible tablet.Yet, when preparing the candesartan Cilexetil dispersible tablet according to the method for prior art, can't reach the effect of disperseing in 3 minutes, become insoluble problem.
The inventor is surprised to find that, adopts technology of the present invention that candesartan Cilexetil is made dispersible tablet, can disperse in 3 minutes.
Summary of the invention
A kind of candesartan Cilexetil dispersible tablet and preparation method thereof that provides of the present invention.
Candesartan Cilexetil dispersible tablet of the present invention, it is characterized in that containing candesartan Cilexetil, the combination of the low-substituted hydroxypropyl cellulose (L-HPC) of one or more adjuvants and 1%-20% in the polyvinylpolypyrrolidone of 1%-20% (PVPP), carboxymethyl starch sodium, the cross-linking sodium carboxymethyl cellulose, the percentage by weight of described each composition is based on the total weight of dispersible tablet.
Candesartan Cilexetil dispersible tablet of the present invention, it is characterized in that containing candesartan Cilexetil, the combination of the low-substituted hydroxypropyl cellulose (L-HPC) of one or more disintegrating agents and 1%-20% in the polyvinylpolypyrrolidone of 1%-15% (PVPP), carboxymethyl starch sodium, the cross-linking sodium carboxymethyl cellulose, the percentage by weight of described each composition is based on the total weight of dispersible tablet.
Wherein the amount of active component candesartan Cilexetil is between 1-20mg, preferably between 4-16mg.
It is 1.0-16.0 weight % that low-substituted hydroxypropyl cellulose can be defined as hydroxypropyl content.
Candesartan Cilexetil dispersible tablet of the present invention further comprises one or more adjuvants such as diluent, fluidizer, lubricant, sweeting agent.
The percentage by weight of each composition is in the candesartan Cilexetil dispersible tablet of the present invention, and based on the total weight of dispersible tablet, the amount of diluent is between 20-95%, preferably between 30-80%; The amount of binding agent is preferably between 0-10%, more preferably between 1.5-5%; The amount of fluidizer is between 0-6%, preferably between 0.1-5%, more preferably between 0.5-3%; The amount of lubricant is between 0-2%, preferably between 0.1-1.5%, more preferably between 0.4-1%.
Suitable diluent includes but not limited to starch, pregelatinized Starch, lactose, microcrystalline Cellulose, mannitol and combination thereof.In preferred use starch, pregelatinized Starch or the lactose one or more and microcrystalline Cellulose combination.
Suitable fluidizer includes but not limited to micropowder silica gel, Pulvis Talci.Preferred use micropowder silica gel.
Suitable lubricant includes but not limited to stearic acid, magnesium stearate, calcium stearate, Pulvis Talci, sodium benzoate, mono fatty acid glyceride, palmitostearate, Polyethylene Glycol.The preferred magnesium stearate of using.
Suitable sweeting agent comprises but is not limited to saccharin sodium, aspartame and sucralose.
In one specific embodiment, the invention provides a kind of candesartan Cilexetil dispersible tablet, contain the polyvinylpolypyrrolidone (PVPP) of candesartan Cilexetil, 1%-20%, low-substituted hydroxypropyl cellulose (L-HPC), microcrystalline Cellulose, lactose, starch or pregelatinized Starch, micropowder silica gel and the magnesium stearate of 1%-20%.In a more particular embodiment, candesartan Cilexetil dispersible tablet of the present invention contains the 1-35% candesartan Cilexetil, low-substituted hydroxypropyl cellulose (L-HPC), 5-45% microcrystalline Cellulose, 5-65% lactose, 10-85% starch or pregelatinized Starch, 0-6% micropowder silica gel, 0-2% magnesium stearate and the 0-1% saccharin sodium of the polyvinylpolypyrrolidone of 1-20% (PVPP), 1-20%.
In another specific embodiment, a kind of candesartan Cilexetil dispersible tablet that provides of the present invention contains the carboxymethyl starch sodium (PVPP) of candesartan Cilexetil, 1%-15%, low-substituted hydroxypropyl cellulose (L-HPC), microcrystalline Cellulose, lactose, starch or pregelatinized Starch, micropowder silica gel and the magnesium stearate of 1%-20%.In a more particular embodiment, candesartan Cilexetil dispersible tablet of the present invention contains the 1-35% candesartan Cilexetil, low-substituted hydroxypropyl cellulose (L-HPC), 5-45% microcrystalline Cellulose, 5-65% lactose, 10-85% starch or pregelatinized Starch, 0-6% micropowder silica gel, 0-2% magnesium stearate and the 0-1% saccharin sodium of the carboxymethyl starch sodium of 1%-15% (PVPP), 1%-20%.
In going back a specific embodiment, the invention provides a kind of candesartan Cilexetil dispersible tablet, contain the cross-linking sodium carboxymethyl cellulose of candesartan Cilexetil, 1%-15%, the low-substituted hydroxypropyl cellulose of 1%-20% (L-HPC), microcrystalline Cellulose, lactose, starch or pregelatinized Starch, micropowder silica gel and magnesium stearate.In a more particular embodiment, candesartan Cilexetil dispersible tablet 1-35% candesartan Cilexetil of the present invention, the cross-linking sodium carboxymethyl cellulose of 1%-15%, the low-substituted hydroxypropyl cellulose of 1%-20% (L-HPC), 5-45% microcrystalline Cellulose, 5-65% lactose, 10 one 85% starch or pregelatinized Starch, 0-6% micropowder silica gel, 0-2% magnesium stearate and 0-1% saccharin sodium.
The present invention also provides the preparation method of candesartan Cilexetil dispersible tablet, comprises following step:
(1) all supplementary materials are crossed 100 mesh sieves, standby.
(2) behind the low-substituted hydroxypropyl cellulose mix homogeneously with candesartan Cilexetil and equivalent, cross 100 mesh sieves, cross 100 mesh sieves again with behind the low-substituted hydroxypropyl cellulose mix homogeneously of mixed powder equivalent.
(3) diluent was done mixed 10 minutes.
(4) candesartan Cilexetil that step (2) is obtained and low-substituted hydroxypropyl cellulose mixed powder and mixing diluents powder are crossed 40 mesh sieves behind the mix homogeneously on year-on-year basis, do and mix 10 minutes.
(5) add the saccharin sodium ethanol water, wet mixing 1-2 minute, granulate with 30 mesh sieves.
(6) granule that makes is dry under 60 ± 5 ℃ of temperature.
(7) dried granule is with 20 mesh sieve granulate.
(8) one or more disintegrating agents in dried granule and the polyvinylpolypyrrolidone of crossing 100 mesh sieves, carboxymethyl starch sodium, the cross-linking sodium carboxymethyl cellulose, fluidizer, mix lubricant are even.
(9) content of candesartan Cilexetil in the mensuration granule determines that sheet is heavy, tabletting.
Candesartan Cilexetil dispersible tablet of the present invention adopts low-substituted hydroxypropyl cellulose and the combination of other disintegrating agent can reach the effect of disperseing in 3 minutes in aqueous medium such as water, and adding microcrystalline Cellulose effect is better in the candesartan Cilexetil dispersible tablet.
Candesartan Cilexetil dispersible tablet of the present invention can be realized the quick disintegrate dispersion of sheet, the fast Absorption of candesartan Cilexetil, has improved the bioavailability of candesartan Cilexetil.
The specific embodiment
Embodiment 1
The composition of table 1. embodiment 1 candesartan Cilexetil dispersible tablet (unit of each composition is mg)
| Component | Embodiment 1 | Reference preparation 1 |
| Candesartan Cilexetil | 4 | 4 |
| Low-substituted hydroxypropyl cellulose | 7.5 | 0 |
| Starch | 68 | 68 |
| Lactose | 22.5 | 60 |
| Microcrystalline Cellulose | 30.5 | 0 |
| Saccharin sodium | 0.15 | 0.15 |
| Polyvinylpolypyrrolidone (PVPP) | 9 | 12 |
| Micropowder silica gel | 0.75 | 0.75 |
| Magnesium stearate | 0.6 | 0.6 |
Be prepared as follows:
(1) various supplementary materials such as the candesartan Cilexetil in will writing out a prescription, low-substituted hydroxypropyl cellulose, lactose, medical starch, microcrystalline Cellulose, polyvinylpolypyrrolidone are crossed 100 mesh sieves, and are standby.
(2) take by weighing the low-substituted hydroxypropyl cellulose mix homogeneously of the candesartan Cilexetil of recipe quantity and equivalent after, cross 100 mesh sieves, cross 100 mesh sieves after taking by weighing the low-substituted hydroxypropyl cellulose mix homogeneously with mixed powder equivalent again.
(3) lactose, medical starch, the microcrystalline Cellulose that takes by weighing recipe quantity done mixed 10 minutes.
(4) take by weighing candesartan Cilexetil and low-substituted hydroxypropyl cellulose mixed powder and lactose, medical starch, microcrystalline Cellulose mixed powder and cross 40 mesh sieves behind the mix homogeneously on year-on-year basis, all supplementary materials are done mixed 10 minutes again.
(5) add the saccharin sodium ethanol water, wet mixing 1-2 minute, granulate with 30 mesh sieves.
(6) granule that makes is dry under 60 ± 5 ℃ of temperature.
(7) dried granule is with 20 mesh sieve granulate.
(8) with dried granule and polyvinylpolypyrrolidone, magnesium stearate, the micropowder silica gel mix homogeneously of crossing 100 mesh sieves.
(9) content of candesartan Cilexetil in the mensuration granule determines that sheet is heavy, tabletting.
(10) packing, warehouse-in.
The preparation of reference preparation 1 preparation did not add the low-substituted hydroxypropyl cellulose in (4) step, and is identical with said method.
Dispersing uniformity and dissolution determination
According to the method for Chinese Pharmacopoeia version in 2010 the candesartan Cilexetil dispersible tablet of embodiment 1 is carried out dispersing uniformity, dissolution determination.
The candesartan Cilexetil dispersible tablet dispersing uniformity of table 2. embodiment 1, dissolution determination result
| ? | Embodiment 1 | Reference preparation 1 |
| Dispersing uniformity | 1 minute 10 seconds | 9 minutes 27 seconds |
| Dissolution % | 98％ | 68％ |
The human pharmacokinetics experiment
Behind the candesartan Cilexetil dispersible tablet formulation and reference preparation of 22 oral embodiment 1 of health volunteer, the Tmax that records Candesartan in the blood plasma is as follows respectively:
The candesartan Cilexetil dispersible tablet of table 3. embodiment 1 and the pharmacokinetic parameter of reference preparation 1
Embodiment 2
The composition of table 4. embodiment 2 candesartan Cilexetil dispersible tablets (unit of each composition is mg)
| Component | Embodiment 2 | Reference preparation 2 |
| Candesartan Cilexetil | 4 | 4 |
| Low-substituted hydroxypropyl cellulose | 7.5 | 7.5 |
| Starch | 68 | 68 |
| Lactose | 22.5 | 60 |
| Microcrystalline Cellulose | 37.5 | 0 |
| Saccharin sodium | 0.15 | 0.15 |
| Carboxymethyl starch sodium | 9 | 9 |
| Micropowder silica gel | 0.75 | 0.75 |
| Magnesium stearate | 0.6 | 0.6 |
Be prepared as follows:
(1) candesartan Cilexetil, low-substituted hydroxypropyl cellulose, lactose, medical starch, microcrystalline Cellulose, the carboxymethyl starch in will writing out a prescription various supplementary materials such as received and crossed 100 mesh sieves, and be standby.
(2) take by weighing the low-substituted hydroxypropyl cellulose mix homogeneously of the candesartan Cilexetil of recipe quantity and equivalent after, cross 100 mesh sieves, cross 100 mesh sieves after taking by weighing the low-substituted hydroxypropyl cellulose mix homogeneously with mixed powder equivalent again.
(3) lactose, medical starch, the microcrystalline Cellulose that takes by weighing recipe quantity done mixed 10 minutes.
(4) take by weighing candesartan Cilexetil and low-substituted hydroxypropyl cellulose mixed powder and lactose, medical starch mixed powder and cross 40 mesh sieves behind the mix homogeneously on year-on-year basis, all supplementary materials are done mixed 10 minutes again.
(5) add the saccharin sodium aqueous solution, wet mixing 1-2 minute, granulate with 30 mesh sieves.
(6) granule that makes is dry under 60 ± 5 ℃ of temperature.
(7) dried granule is with 20 mesh sieve granulate.
(8) dried granule and the carboxymethyl starch of crossing 100 mesh sieves are received, magnesium stearate, micropowder silica gel, microcrystalline Cellulose mix homogeneously.
(9) content of candesartan Cilexetil in the mensuration granule determines that sheet is heavy, tabletting.
(10) packing, warehouse-in.
The preparation of reference preparation 2 preparations did not add the low-substituted hydroxypropyl cellulose in (4) step, and is identical with said method.
According to the method for Chinese Pharmacopoeia version in 2010 the candesartan Cilexetil dispersible tablet of embodiment 2 is carried out dispersing uniformity, dissolution determination.
The candesartan Cilexetil dispersible tablet dispersing uniformity of table 5. embodiment 2, dissolution determination result
| ? | Embodiment 2 | Reference preparation 2 |
| Dispersing uniformity | 1 minute 26 seconds | 7 minutes 27 seconds |
| Dissolution % | 95％ | 72％ |
The human pharmacokinetics experiment
Adopt the method identical with embodiment 1 that candesartan Cilexetil dispersible tablet formulation and the reference preparation 2 of embodiment 2 are experimentized.
The candesartan Cilexetil dispersible tablet of table 6. embodiment 2 and the pharmacokinetic parameter of reference preparation 2
Embodiment 3
The composition of table 7. embodiment 3 candesartan Cilexetil dispersible tablets (unit of each composition is mg)
| Component | Embodiment 3 | Reference preparation 3 |
| Candesartan Cilexetil | 4 | 4 |
| Low-substituted hydroxypropyl cellulose | 7.5 | 105.5 |
| Starch | 68 | 68 |
| Lactose | 22.5 | 67.5 |
| Microcrystalline Cellulose | 37.5 | 0 |
| Saccharin sodium | 0.15 | 0.15 |
| Cross-linking sodium carboxymethyl cellulose | 9 | 9 |
| Micropowder silica gel | 0.75 | 0.75 |
| Magnesium stearate | 0.6 | 0.6 |
Be prepared as follows:
(1) various supplementary materials such as the candesartan Cilexetil in will writing out a prescription, low-substituted hydroxypropyl cellulose, lactose, medical starch, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose are crossed 100 mesh sieves, and are standby.
(2) take by weighing the low-substituted hydroxypropyl cellulose mix homogeneously of the candesartan Cilexetil of recipe quantity and equivalent after, cross 100 mesh sieves, cross 100 mesh sieves after taking by weighing the low-substituted hydroxypropyl cellulose mix homogeneously with mixed powder equivalent again.
(3) lactose, medical starch, the microcrystalline Cellulose that takes by weighing recipe quantity done mixed 10 minutes.
(4) take by weighing candesartan Cilexetil and low-substituted hydroxypropyl cellulose mixed powder and lactose, medical starch mixed powder and cross 40 mesh sieves behind the mix homogeneously on year-on-year basis, all supplementary materials are done mixed 10 minutes again.
(5) add the saccharin sodium aqueous solution, wet mixing 1-2 minute, granulate with 30 mesh sieves.
(6) granule that makes is dry under 60 ± 5 ℃ of temperature.
(7) dried granule is with 20 mesh sieve granulate.
(8) with dried granule and cross-linking sodium carboxymethyl cellulose, magnesium stearate, micropowder silica gel, the microcrystalline Cellulose mix homogeneously of crossing 100 mesh sieves.
(9) content of candesartan Cilexetil in the mensuration granule determines that sheet is heavy, tabletting.
(10) packing, warehouse-in.
The preparation of reference preparation 3 did not add the low-substituted hydroxypropyl cellulose in (4) step, and is identical with said method.
According to the method for Chinese Pharmacopoeia version in 2010 the candesartan Cilexetil dispersible tablet of embodiment 3 is carried out dispersing uniformity, dissolution determination.
The candesartan Cilexetil dispersible tablet dispersing uniformity of table 8. embodiment 3, dissolution determination result
| ? | Embodiment 3 | Reference preparation 3 |
| Dispersing uniformity | 1 minute 50 seconds | 7 minutes 12 seconds |
| Dissolution % | 93％ | 78％ |
The human pharmacokinetics experiment
Adopt the method identical with embodiment 1 that candesartan Cilexetil dispersible tablet formulation and the reference preparation 3 of embodiment 3 are experimentized.
The candesartan Cilexetil dispersible tablet of table 9. embodiment 3 and the pharmacokinetic parameter of reference preparation 3
Candesartan Cilexetil dispersible tablet disintegrate of the present invention disperses soon, dissolution is fast, the bioavailability height.
Claims (8)
1. candesartan Cilexetil dispersible tablet, it is characterized in that containing candesartan Cilexetil, the combination of the low-substituted hydroxypropyl cellulose (L-HPC) of one or more adjuvants and 1%-20% in the polyvinylpolypyrrolidone of 1%-20% (PVPP), carboxymethyl starch sodium, the cross-linking sodium carboxymethyl cellulose, the percentage by weight of described each composition is based on the total weight of dispersible tablet.
2. the candesartan Cilexetil dispersible tablet of claim 1 further contains one or more adjuvants in diluent, fluidizer, lubricant, the sweeting agent.
3. the candesartan Cilexetil dispersible tablet of claim 1-2, based on the total weight of dispersible tablet, the amount of diluent is between 20-95%, preferably between 30-80%; The amount of binding agent is preferably between 0-10%, more preferably between 1.5-5%; The amount of fluidizer is between 0-6%, preferably between 0.1-5%, more preferably between 0.5-3%; The amount of lubricant is between 0-2%, preferably between 0.1-1.5%, more preferably between 0.4-1%.
4. the candesartan Cilexetil dispersible tablet of claim 1 further contains microcrystalline Cellulose.
5. the candesartan Cilexetil dispersible tablet of claim 1-4, total weight based on dispersible tablet, contain the 1-35% candesartan Cilexetil, low-substituted hydroxypropyl cellulose (L-HPC), 5-45% microcrystalline Cellulose, 5-65% lactose, 10-85% starch or pregelatinized Starch, 0-6% micropowder silica gel and the 0-2% magnesium stearate of the polyvinylpolypyrrolidone of 1-20% (PVPP), 1-20%.
6. the candesartan Cilexetil dispersible tablet of claim 1-4, total weight based on dispersible tablet, contain the 1-35% candesartan Cilexetil, low-substituted hydroxypropyl cellulose (L-HPC), 5-45% microcrystalline Cellulose, 5-65% lactose, 10-85% starch or pregelatinized Starch, 0-6% micropowder silica gel and the 0-2% magnesium stearate of the carboxymethyl starch sodium of 1%-15% (PVPP), 1%-20%.
7. the candesartan Cilexetil dispersible tablet of claim 1-4, total weight based on dispersible tablet, contain the 1-35% candesartan Cilexetil, the cross-linking sodium carboxymethyl cellulose of 1%-15%, the low-substituted hydroxypropyl cellulose of 1%-20% (L-HPC), 5-45% microcrystalline Cellulose, 5-65% lactose, 10-85% starch or pregelatinized Starch, 0-6% micropowder silica gel and 0-2% magnesium stearate.
8. the preparation method of the candesartan Cilexetil dispersible tablet of claim 1 comprises following step:
(1) all supplementary materials are crossed 100 mesh sieves, standby.
(2) behind the low-substituted hydroxypropyl cellulose mix homogeneously with candesartan Cilexetil and equivalent, cross 100 mesh sieves, cross 100 mesh sieves again with behind the low-substituted hydroxypropyl cellulose mix homogeneously of mixed powder equivalent.
(3) diluent was done mixed 10 minutes.
(4) candesartan Cilexetil that step (2) is obtained and low-substituted hydroxypropyl cellulose mixed powder and mixing diluents powder are crossed 40 mesh sieves behind the mix homogeneously on year-on-year basis, do and mix 10 minutes.
(5) add the saccharin sodium ethanol water, wet mixing 1-2 minute, granulate with 30 mesh sieves.
(6) granule that makes is dry under 60 ± 5 ℃ of temperature.
(7) dried granule is with 20 mesh sieve granulate.
(8) one or more disintegrating agents in dried granule and the polyvinylpolypyrrolidone of crossing 100 mesh sieves, carboxymethyl starch sodium, the cross-linking sodium carboxymethyl cellulose, fluidizer, mix lubricant are even.
(9) content of candesartan Cilexetil in the mensuration granule determines that sheet is heavy, tabletting.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104688696A (en) * | 2013-12-04 | 2015-06-10 | 长春海悦药业有限公司 | Pharmaceutical composition containing candesartan cilexetil |
-
2013
- 2013-04-17 CN CN2013101317298A patent/CN103284966A/en active Pending
Non-Patent Citations (4)
| Title |
|---|
| ATHEER MOHAMMED JASEM ET.AL: "PREPARATION AND CHARACTERIZATION OF ORODISPERSIBLE TABLETS OF CANDESARTAN CILEXETIL BY DIRECT COMPRESSION METHOD", 《INTERNATIONAL JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES》 * |
| BASAWARAJ S.PATIL ET.AL: "FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF CANDESARTAN CILEXETIL USING NATURAL AND SYNTHETIC SUPERDISINTEGRANTS", 《J APP PHARM》 * |
| 王玉玲: "分散片中的崩解剂", 《食品与药品》 * |
| 白慧东等: "几种分散片崩解剂的性能与应用现状", 《新疆医学》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104688696A (en) * | 2013-12-04 | 2015-06-10 | 长春海悦药业有限公司 | Pharmaceutical composition containing candesartan cilexetil |
| CN104688696B (en) * | 2013-12-04 | 2017-12-19 | 长春海悦药业股份有限公司 | A kind of pharmaceutical composition containing candesartan Cilexetil |
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