CN105158188A - Release detection method of aniracetam sustained release tablet - Google Patents
Release detection method of aniracetam sustained release tablet Download PDFInfo
- Publication number
- CN105158188A CN105158188A CN201510390052.9A CN201510390052A CN105158188A CN 105158188 A CN105158188 A CN 105158188A CN 201510390052 A CN201510390052 A CN 201510390052A CN 105158188 A CN105158188 A CN 105158188A
- Authority
- CN
- China
- Prior art keywords
- release
- anixitan
- releasing
- slow
- detection method
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Belonging to the technical field of drugs, the invention discloses a release detection method of an aniracetam sustained release tablet. The release detection method of the aniracetam sustained release tablet comprises the steps of: 1) in vitro dissolution rate test of the aniracetam sustained release tablet; 2) determination of in vivo blood concentration; and 3) in vitro-in vivo correlation analysis. The invention constructs in vitro evaluation model simulating the in vivo, establishes an in vitro-in vivo correlation multi-criteria evaluation technology, increases new evaluation indexes, and establishes a new detection method, better explains advantages of the prescription, establishes an evaluation technique suitable for drugs with too quick prototype drug release, and provides the basis and guidance for study of the drug in future.
Description
Technical field
The invention belongs to technical field of pharmaceuticals, particularly a kind of release detection method of slow-releasing Anixitan tablet.
Background technology
Aniracetam is as a kind of important medicine for the treatment of senile dementia, and it learns light moderate, the handicapped vascular dementia of memory and cognition and Alzheimer disease, post-stroke light moderate cognitive in various degree and behavior disorder, person in middle and old age's benign memory deficits have obvious therapeutic action.At present, the commercial dosage forms of Aniracetam mainly contains tablet, granule and dispersing tablet, mostly is regular dosage form, all there is the defects such as taking dose is large, the half life period is shorter, medicining times is more, brings inconvenience to the treatment of senile dementia disease and patient consumes.
Sustained release preparation refer to oral after in regulation release medium, on request lentamente non-constant velocity release medicine, compare with corresponding ordinary preparation, administration frequency at least reduces half or reduces to some extent, and significantly can increase the compliance of patient or the preparation of curative effect.Sustained release preparation can reduce administration frequency, facilitates patient to take, and can improve curative effect, reduces blood concentration fluctuation, reduces toxic and side effect.
At present, the release detection method to slow-releasing Anixitan tablet of good system is not also had.
Summary of the invention
The object of the invention is to overcome the shortcoming that exists in above-mentioned prior art with not enough, a kind of release detection method of slow-releasing Anixitan tablet is provided.
Object of the present invention is achieved through the following technical solutions: a kind of release detection method of slow-releasing Anixitan tablet, comprises the following steps:
1) the dissolution in vitro experiment of slow-releasing Anixitan tablet
According to official method, select to adopt ultraviolet spectrophotometry to carry out full wavelength scanner, determine the uv-absorption maximum wavelength of Aniracetam; Adopt slurry processes, be release medium at hydrochloric acid solution, acetate buffer, phosphate buffer, water 900mL respectively, measure the release with a collection of sustained release tablets, investigate medium to the impact of main ingredient release; Adopt release inspection technique, in different time points sampling, measure its absorbance, record data, calculate accumulative release rate, in this, as Testing index, investigate the impact of rotating speed on main ingredient release; After determining above condition, get 6 slow-releasing Anixitan tablets, adopt above method to measure the absorbance of different time points, calculate stripping percent, investigate release homogeneity;
2) mensuration of blood concentration in body
This experiment adopts rabbit as experimental subjects, tests after giving oral administration with rabbit, respectively at different time points blood sample collection, the blood sample gathered is put in the wetting centrifuge tube of liquaemin centrifugal, gets supernatant, pipettes a certain amount of blood plasma, after organic solvent extractionprocess process, for subsequent use; Adopt the blood concentration of high effective liquid chromatography for measuring different time points, record chromatogram, calculates relevant pharmacokinetic parameter;
3) In vitro-in vivo correlation analysis
Adopt models fitting absorption fraction method, the blood concentration-time data 3P97 pharmacokinetics program of slow-releasing Anixitan tablet is simulated, meets first order kinetics, be judged to be one compartment model according to AIC method, obtain the K of every rabbit respectively
evalue is averaged again, obtains the elimination rate constant of slow-releasing Anixitan tablet; Adopt Wagner-Nelson method to press one compartment model and calculate body absorption mark; Take Cumulated released percent in vitro as independent variable, body absorption mark is dependent variable, carries out least square method linear regression, tries to achieve dependent equation and related coefficient, judges in body and the correlativity of Absorption in vitro; As a result, the equation doing linear regression is Y=1.0635X+9.675, R=0.9630; Look into correlation coefficient charts to obtain, r0.01=0.7545<R=0.9630; Man-to-man relevant to bioavilability in body by In Vitro Dissolution, namely by In Vitro Dissolution, drug quality is controlled, just can ensure medicine performance in vivo.
Step 1) described in the pH value of hydrochloric acid solution be 1.0.
Step 1) described in the pH value of acetate buffer be 3.6.
Step 1) described in the pH value of phosphate buffer be 7.0.
Step 1) described in different time points be sampled as and sample respectively at 1h, 2h, 4h, 6h, 8h, 10h and 12h.
Step 2) described in be the blood sample collection respectively of 10min, 20min, 30min, 40min, 120min, 160min, 240min, 360min, 540min and 720min after taking medicine respectively at different time points blood sample collection.
Compared with prior art, the assessment technique of the slow-releasing Anixitan tablet that the present invention relates to has technique effect useful as follows:
(1) evaluation model in in-vitro simulated body is constructed.Limit is 1 hour release 25-40%, 4 hours release 55-80%, release more than 80% in 8 hours.
(2) establish In vitro-in vivo correlation multiple index evaluation technology, add new evaluation index, and establish new detection method.
(3) better explain the advantage of prescription, establish a kind of assessment technique being applicable to the too fast medicine of proto-drug release, for the research of this kind of medicine from now on provides foundation and guidance.
(4) method that present invention employs In vitro-in vivo correlation experiment determines the drug release behavior rating technique of slow-releasing Anixitan tablet.Results of in vitro studies can be used to evaluate drug effect measurement.Good stability, the release of this assessment technique are good, are conducive to Clinical practice.The inventive method is simple to operate, and the large-scale industrial being convenient to this sustained release tablets is produced, and has larger using value.
Accompanying drawing explanation
Fig. 1 is Aniracetam UV scanning figure.
Fig. 2 is that different rotating speeds affects result figure to main ingredient release.
Fig. 3 is the releasing curve diagram of 6 samples.
Fig. 4 is that slow-releasing Anixitan tablet adds up release rate result figure.
Fig. 5 is the Drug-time curve figure of Aniracetam ordinary tablet and sustained release tablets.
Embodiment
Below in conjunction with embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention are not limited thereto.
Embodiment 1
Release detection method
A kind of release detection method of slow-releasing Anixitan tablet
(1) selection of maximum absorption wavelength
Precision takes Aniracetam reference substance 5.02mg, put in 50ml volumetric flask, add a small amount of ethanol to dissolve, be diluted to scale with hydrochloric acid solution (9 → 1000), draw 1.0mL and put in 100mL measuring bottle, be diluted to scale with hydrochloric acid solution (9 → 1000), according to " Chinese Pharmacopoeia " version annex IV A ultraviolet spectrophotometry in 2010, carry out UV scanning, result has absorption maximum at 282nm, therefore selects determined wavelength to be 282nm.See Fig. 1.
(2) rotating speed is on the impact of main ingredient release
Get this product, according to drug release determination method, adopt drug release determination method (Chinese Pharmacopoeia 2010 editions two annex XD second methods) device with water 900mL for release medium, rotating speed is 50 turns per minute, 100 turns and operates in accordance with the law, and method is with reference to above-mentioned drug release determination method.Arranging rotating speed is respectively 50 turns and 100 turns per minute, operates in accordance with the law, respectively at 1,2,4,8,10,12 hour, gets solution 10mL (simultaneously adding the blank dissolution medium 10mL of identical temperature), filters; Separately get Aniracetam reference substance appropriate, accurately weighed, also quantitatively dilute by water-soluble solution and make every 1mL about containing the solution product solution in contrast of 0.1mg.Get above-mentioned two kinds of solution, carry out absorbance measurement at the wavelength place of 282nm respectively, calculate release percent, draw release profiles.See Fig. 2.
As seen from the figure, the release of 50 turns per minute is more lower slightly than the release of 100 turns per minute, so select rotating speed to be 100 turns per minute.
(3) uniformity test is discharged
Get this product 6 with water 900mL for solvent, rotating speed is 100 turns per minute, operates in accordance with the law, respectively at 1,2,4,8,10,12 hour, get solution 10mL (simultaneously adding the blank release medium 10mL of identical temperature), filter, get subsequent filtrate as need testing solution; Separately get Aniracetam reference substance and be about 10mg, add appropriate amount of ethanol and dissolve, be diluted to every milliliter with 0.1mol/L hydrochloric acid solution and about measure absorbance containing the reference substance solution of 10 μ g, calculate stripping percent, draw stripping curve.
Get above-mentioned two kinds of solution, measure absorbance at the wavelength place of 282nm.Release profiles is measured to 6, sample.See Fig. 3.
Result: adopt this method test, discharge in batch all-property is good.
With reference to drug release determination method (Chinese Pharmacopoeia version in 2010 two annex XD first methods), with 0.1mol/L hydrochloric acid solution 900ml for solvent, rotating speed is 100 turns/min, temperature is set to 37 DEG C, every 1 hour, get solution 10ml, filter, and supply dissolution medium with the taking-up synthermal hydrochloric acid solution of solution same volume (9 → 1000), precision measures subsequent filtrate 5ml, is placed in 50ml volumetric flask, quantitatively scale is diluted to above-mentioned dissolution medium, shake up, as need testing solution, get 10 time points altogether and mark respectively; Separately get Aniracetam reference substance 50mg, accurately weighed, add after ethanol 10ml makes dissolving, be quantitatively diluted to the solution about containing 10ug in every 1ml with above-mentioned solvent, product solution in contrast.Get above-mentioned test sample and reference substance solution, measure its absorbance at the wavelength place of 282nm respectively, calculate the accumulative release rate of every sheet.As shown in Figure 4, limit is 1 hour release 25-40%, 4 hours release 55-80%, release more than 80% in 8 hours.
2 pharmacokinetics
The relevant references of consulting Aniracetam is known, and after Aniracetam is taken, the former medicine metabolism of about 70% is ABA, and proto-drug concentration is extremely low, is difficult to detect.So this test illustrates the pharmacokinetics behavior of Aniracetam in rabbit body with the assay situation of ABA.
(1) administration and sample collection
Healthy rabbits 6, female half and half, body weight is all about 2.5kg, and gavage two panels self-control Aniracetam sheet (being about equivalent to Aniracetam main ingredient 200mg) after fasting 10h, suitable quantity of water is taken after mixing it with water.Ordinary tablet is after taking medicine after 10,20,30,40,120,160,240,360,540,720min, and each time point respectively auricular vein gets blood 1.5mL; Sustained release tablets is after taking medicine after 10,20,30,40,120,160,240,360,540,720min, and each time point respectively auricular vein gets blood 1.5mL; Be put in the centrifuge tube containing 0.1mL heparin, the centrifugal 10min of 3000r/min, blood plasma taking-up be put in-20 DEG C of frozen coatings and preserve to be measured.After 4h, feeding drinking-water is carried out in unification.
(2) assay method
Chromatographic column: PhenomenexUP-ODSC18 post (250 × 4.6mm, 5 μm)
Mobile phase ratio: acetonitrile-0.1% acetic acid (25:75)
Column temperature: 35 DEG C
Flow velocity: 1.0mL/min
Determined wavelength: 250nm
Sample size: 20 μ L
(3) preparation of reference substance and sample solution
The preparation of ABA mother liquor: precision takes ABA reference substance and is about 5mg, puts in 50mL measuring bottle, uses acetonitrile constant volume, obtains the ABA storing solution that concentration is 100 μ g/mL.For subsequent use.
The preparation of Hydrochioro standard solution: precision takes Hydrochioro reference substance and is about 2mg in 10mL volumetric flask, dissolve and constant volume with acetonitrile, the concentration obtained is the Hydrochioro storing solution of 200 μ g/mL, by dilution in acetonitrile, finally join concentration is the Hydrochioro solution of 20 μ g/mL, as interior mark liquid, be placed in 4 DEG C of Refrigerator stores, for subsequent use.
(4) process of plasma sample
Essence is got blood plasma 0.3mL and is put in 1.5mL centrifuge tube, add 1mL (ethyl acetate: acetonitrile=8:2), vortex oscillation 5min, centrifugal (12000r/min, 10min), essence gets supernatant 1mL, put in 5mL centrifuge tube, 50 DEG C of water-baths, nitrogen dries up, residue 200 μ L acetonitriles dissolve, and get 20 μ L sample introductions.
(5) drug-time curve of the normal sheet of Aniracetam and sustained release tablets compares
By 6 healthy rabbits, be divided into 2 groups, one group to Aniracetam ordinary tablet, one group to slow-releasing Anixitan tablet.Repeat 2 cycles, each cycle midfeather one week.Record the blood concentration of ordinary tablet and sustained release tablets respectively, the drug-time curve of both draftings, as shown in Figure 5.
3 vivo and vitro correlation researchs
This experiment have employed room model and relies on method, and application Wagner-Nelson method tries to achieve the absorption fraction of different time.Fitting result through compartment model is known, and this is tested homemade slow-releasing Anixitan tablet and meets one compartment model, and therefore apply the drug absorption mark that Wagner-Nelson method tries to achieve different time, formula is as follows:
Fa＝(Ct+KeAUC0-t)/KeAUC0-∞×100％
The result of the inside and outside of homemade slow-releasing Anixitan tablet is as following table 1.
Table 1 slow-releasing Anixitan tablet inside and outside related data
Take Cumulated released percent in vitro as independent variable.Body absorption mark is dependent variable, carries out least square method linear regression, tries to achieve dependent equation and related coefficient, judges in body and the correlativity of Absorption in vitro.As a result, the equation doing linear regression is Y=1.0635X+9.675, R=0.9630.Look into correlation coefficient charts to obtain, r0.01=0.7545<R=0.9630.The correlativity of slow-releasing Anixitan tablet inside and outside is good as can be seen here.
Above-described embodiment is the present invention's preferably embodiment; but embodiments of the present invention are not restricted to the described embodiments; change, the modification done under other any does not deviate from Spirit Essence of the present invention and principle, substitute, combine, simplify; all should be the substitute mode of equivalence, be included within protection scope of the present invention.
Claims (6)
1. a release detection method for slow-releasing Anixitan tablet, is characterized in that: comprise the following steps:
1) the dissolution in vitro experiment of slow-releasing Anixitan tablet
According to official method, select to adopt ultraviolet spectrophotometry to carry out full wavelength scanner, determine the uv-absorption maximum wavelength of Aniracetam; Adopt slurry processes, be release medium at hydrochloric acid solution, acetate buffer, phosphate buffer, water 900mL respectively, measure the release with a collection of sustained release tablets, investigate medium to the impact of main ingredient release; Adopt release inspection technique, in different time points sampling, measure its absorbance, record data, calculate accumulative release rate, in this, as Testing index, investigate the impact of rotating speed on main ingredient release; After determining above condition, get 6 slow-releasing Anixitan tablets, adopt above method to measure the absorbance of different time points, calculate stripping percent, investigate release homogeneity;
2) mensuration of blood concentration in body
This experiment adopts rabbit as experimental subjects, tests after giving oral administration with rabbit, respectively at different time points blood sample collection, the blood sample gathered is put in the wetting centrifuge tube of liquaemin centrifugal, gets supernatant, pipettes a certain amount of blood plasma, after organic solvent extractionprocess process, for subsequent use; Adopt the blood concentration of high effective liquid chromatography for measuring different time points, record chromatogram, calculates relevant pharmacokinetic parameter;
3) In vitro-in vivo correlation analysis
Adopt models fitting absorption fraction method, the blood concentration-time data 3P97 pharmacokinetics program of slow-releasing Anixitan tablet is simulated, meets first order kinetics, be judged to be one compartment model according to AIC method, obtain the K of every rabbit respectively
evalue is averaged again, obtains the elimination rate constant of slow-releasing Anixitan tablet; Adopt Wagner-Nelson method to press one compartment model and calculate body absorption mark; Take Cumulated released percent in vitro as independent variable, body absorption mark is dependent variable, carries out least square method linear regression, tries to achieve dependent equation and related coefficient, judges in body and the correlativity of Absorption in vitro; As a result, the equation doing linear regression is Y=1.0635X+9.675, R=0.9630; Look into correlation coefficient charts to obtain, r0.01=0.7545<R=0.9630; Man-to-man relevant to bioavilability in body by In Vitro Dissolution, namely by In Vitro Dissolution, drug quality is controlled, just can ensure medicine performance in vivo.
2. the release detection method of slow-releasing Anixitan tablet according to claim 1, is characterized in that: step 1) described in the pH value of hydrochloric acid solution be 1.0.
3. the release detection method of slow-releasing Anixitan tablet according to claim 1, is characterized in that: step 1) described in the pH value of acetate buffer be 3.6.
4. the release detection method of slow-releasing Anixitan tablet according to claim 1, is characterized in that: step 1) described in the pH value of phosphate buffer be 7.0.
5. the release detection method of slow-releasing Anixitan tablet according to claim 1, is characterized in that: step 1) described in different time points be sampled as and sample respectively at 1h, 2h, 4h, 6h, 8h, 10h and 12h.
6. the release detection method of slow-releasing Anixitan tablet according to claim 1, is characterized in that: step 2) described in be the blood sample collection respectively of 10min, 20min, 30min, 40min, 120min, 160min, 240min, 360min, 540min and 720min after taking medicine respectively at different time points blood sample collection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510390052.9A CN105158188A (en) | 2015-07-06 | 2015-07-06 | Release detection method of aniracetam sustained release tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510390052.9A CN105158188A (en) | 2015-07-06 | 2015-07-06 | Release detection method of aniracetam sustained release tablet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105158188A true CN105158188A (en) | 2015-12-16 |
Family
ID=54799123
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510390052.9A Pending CN105158188A (en) | 2015-07-06 | 2015-07-06 | Release detection method of aniracetam sustained release tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105158188A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110675961A (en) * | 2019-08-13 | 2020-01-10 | 中南大学 | Method for estimating area under zidovudine time curve |
| CN112067567A (en) * | 2020-09-09 | 2020-12-11 | 南京中医药大学 | Substance group dissolution kinetics research method of compound salvia tablets |
| CN112816637A (en) * | 2020-06-17 | 2021-05-18 | 湖南慧泽生物医药科技有限公司 | In-vitro dissolution method of mycophenolate mofetil tablets |
| CN115598262A (en) * | 2022-11-24 | 2023-01-13 | 则正（济南）生物科技有限公司（Cn） | Method for evaluating internal and external correlation of diclofenac sodium sustained-release tablets |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040115822A1 (en) * | 2002-09-12 | 2004-06-17 | Schapaugh Randal Lee | Methods of measuring the dissolution rate of an analyte in a non-aqueous liquid composition |
| CN102175823A (en) * | 2010-12-30 | 2011-09-07 | 吉林大学 | Evaluation method for in vitro dissolution analysis of traditional Chinese medicine |
| CN103076410A (en) * | 2013-01-06 | 2013-05-01 | 江苏长泰药业有限公司 | Dissolution rate detection method for simvastatin |
-
2015
- 2015-07-06 CN CN201510390052.9A patent/CN105158188A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040115822A1 (en) * | 2002-09-12 | 2004-06-17 | Schapaugh Randal Lee | Methods of measuring the dissolution rate of an analyte in a non-aqueous liquid composition |
| CN102175823A (en) * | 2010-12-30 | 2011-09-07 | 吉林大学 | Evaluation method for in vitro dissolution analysis of traditional Chinese medicine |
| CN103076410A (en) * | 2013-01-06 | 2013-05-01 | 江苏长泰药业有限公司 | Dissolution rate detection method for simvastatin |
Non-Patent Citations (2)
| Title |
|---|
| LI JUAN等: "Pharmacokinetics and in vitro-in vivo correlation evaluation of self-emulsifying drug delivery system and conventional tablets of aniracetam", 《中国临床药理学与治疗学》 * |
| 卜秋霞等: "吡拉西坦缓释胶囊在家犬体内的药物动力学与相对生物利用度", 《沈阳药科大学学报》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110675961A (en) * | 2019-08-13 | 2020-01-10 | 中南大学 | Method for estimating area under zidovudine time curve |
| CN112816637A (en) * | 2020-06-17 | 2021-05-18 | 湖南慧泽生物医药科技有限公司 | In-vitro dissolution method of mycophenolate mofetil tablets |
| CN112067567A (en) * | 2020-09-09 | 2020-12-11 | 南京中医药大学 | Substance group dissolution kinetics research method of compound salvia tablets |
| CN115598262A (en) * | 2022-11-24 | 2023-01-13 | 则正（济南）生物科技有限公司（Cn） | Method for evaluating internal and external correlation of diclofenac sodium sustained-release tablets |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105158188A (en) | Release detection method of aniracetam sustained release tablet | |
| CN102854281B (en) | Detection method of sugar-free strong loquat syrup | |
| CN106018586A (en) | Method for simultaneously detecting seven sleep chemical medicines | |
| CN109406690A (en) | A kind of method in relation to substance in detection chloraldurate | |
| Vejendla et al. | Method development and validation for Cabotegravir and Rilpivirine by using HPLC and its degradants are characterized by LCMS and FTIR | |
| Gong et al. | Miniaturized ionic liquid dispersive liquid–liquid microextraction in a coupled-syringe system combined with UV for extraction and determination of danazol in danazol capsule and mice serum | |
| CN105510488B (en) | A kind of finger-print and its quality determining method for relieving pain patch | |
| Helmy et al. | In vitro dissolution similarity as a surrogate for in vivo bioavailability and therapeutic equivalence | |
| CN104155383B (en) | The detection method of blue or green Pu granule | |
| CN112816596A (en) | Method for measuring external dissolution degree of nifedipine controlled release tablet | |
| CN105974014A (en) | Method for detecting rhizome anemarrhenae by quantitative analysis of multi-components by single marker | |
| CN102175823A (en) | Evaluation method for in vitro dissolution analysis of traditional Chinese medicine | |
| Çelebier et al. | UV spectrophotometric method for determination of the dissolution profile of rivaroxaban | |
| CN104730167B (en) | A kind of hydrochloric acid lorcaserin enantiomerism body detecting method and quality control standard thereof | |
| CN105004803B (en) | The liquid-phase chromatography method of multiple impurity in a kind of separation determination tolvaptan | |
| CN106018625A (en) | Method for detecting eucalyptol in moxa sticks | |
| CN103837636B (en) | HPTLC (high performance thin layer chromatography) quality evaluation method of Xinfeng capsule by adopting coix seeds as reference | |
| CN105223326A (en) | A kind of vitro classification method of active component in extract oral quick releasing formulation | |
| Zhu et al. | The establish of the HPLC method to examine the plasma concentration of lamotrigine and oxcarbazepine. | |
| CN104569172A (en) | Method for detecting dissolution rate of alogliptin benzoate tablets by using liquid chromatography | |
| CN104914174A (en) | Content determination method of gingko diterpene lactone for injection | |
| CN105628807B (en) | A kind of quality determining method of the amino piperidines of 1 Boc 4 | |
| CN105380912B (en) | A kind of pharmaceutical composition containing Tadalafei | |
| CN104345115B (en) | A kind of method for qualitative and quantitative detection of Kanggu-Zengsheng tablet | |
| CN103364517A (en) | Analysis method for contents of active components in benthiavalicarb.isopropyl-dimethomorph compound preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20151216 |