CN108434110B - Misoprostol composition, tablet and application thereof - Google Patents
Misoprostol composition, tablet and application thereof Download PDFInfo
- Publication number
- CN108434110B CN108434110B CN201810396645.XA CN201810396645A CN108434110B CN 108434110 B CN108434110 B CN 108434110B CN 201810396645 A CN201810396645 A CN 201810396645A CN 108434110 B CN108434110 B CN 108434110B
- Authority
- CN
- China
- Prior art keywords
- misoprostol
- microcrystalline cellulose
- grain diameter
- average grain
- tablet
- 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.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/04—Drugs for genital or sexual disorders; Contraceptives for inducing labour or abortion; Uterotonics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of Misoprostol compositions, tablet and application thereof, prepare the composition using the microcrystalline cellulose formula direct tablet compressing of different-grain diameter, effectively avoid the problem of material is layered in tableting process in production.It is dissolved out according to Misoprostol tablet produced by the present invention with fater disintegration, the characteristics of uniform content, simple production process is suitble to industrialized production.
Description
Technical field
The present invention relates to a kind of Misoprostol compositions, tablet and application thereof.
Background technique
Misoprostol belongs to a kind of artificial synthesized active derivatives of prostaglandins, in 1985 by Britain
Searle exploitation listing, initially clinically for treating duodenal ulcer caused by non-steroidal anti-inflammatory drug and gastric ulcer,
Later with mifepristone close it is sequential merge use, for terminating the early pregnancy in menopause 49 days.
Direct powder compression refers to the side for directly mixture of drug and auxiliary material being carried out without pelletization tabletting
Method.Technique of direct powder compression avoids pelletization, and with time-saving energy-saving, simple process, process is few, is suitable for damp and hot shakiness
The advantages that fixed drug, but there is also more demanding to material fluidity, compressibility and mouldability, it is uneven that material is easy mixing
One, auxiliary material, which is easy to happen lamination, in tableting processes leads to problems such as tablet content uneven.
U.S. Food and Drug Administration (FDA) evaluates data (Review) page 79 and discloses on December 27th, 1988
Original grinds the prescription Misoprostol hypromellose 20.2mg of medicine, microcrystalline cellulose 175.8mg, sodium carboxymethyl starch
3.0mg, rilanit special 1.0mg.It is found in research process, when the microcrystalline cellulose for the use of average grain diameter (D50) being 180 μm
When, the tableting processes tablet content uniformity is unqualified, and material has the tendency that layering, but dissolution curve can be ground unanimously with original；When
When using 50 μm of average grain diameter (D50) of microcrystalline cellulose, the tablet content uniformity is qualified in tableting processes, and material is not stratified,
But dissolution curve ground with original it is inconsistent, hence it is evident that it is partially slow.Be used alone a kind of microcrystalline cellulose be unable to satisfy uniformity of dosage units and
Dissolution curve two indices are all qualified.
The original of Britain PHARMACIA production, which is ground after medicine specification shows the product oral, to be absorbed rapidly, it is lived after 30 minutes
Property metabolin blood concentration reach to peak value, plasma clearance half-life period of the active metabolite is 20-40 minutes.The original grinds medicine dissolution
Speed is very fast, and for the requirement for reaching bioequivalence, the dissolution rate of imitation medicine also should be very fast and grinds medicine trend with original and want one
It causes.Inventor has found the microcrystalline cellulose using single particle size by describe before can not when prescription prepares tablet in the course of the research
Take into account uniform content and Fast Stripping.
Summary of the invention
Present invention aim to address being in a liquid state under current Misoprostol composition room temperature state, and water unstable is met,
The easy mixing of direct powder compression material is inhomogenous, and auxiliary material, which is easy to happen lamination, in tableting processes leads to tablet content not
Uniform technical problem.
To realize the above goal of the invention, in a first aspect, the present invention provides a kind of Misoprostol composition, comprising such as the following group
Point:
Wherein, Misoprostol content is 1% in the Misoprostol hypromellose compound, described micro-
1 average grain diameter of crystalline cellulose (D50) is 50-90 μm, and 2 average grain diameter of microcrystalline cellulose (D50) is 160-180 μm.
Further, the average grain diameter (D50) of the Misoprostol hypromellose compound is 50-200 μm,
It is preferred that 80-150 μm.
Further, the microcrystalline cellulose 2 is with the mass ratio of microcrystalline cellulose 1 in 3.4:1-1:1, preferably 2:1-1:1.
Further, the disintegrating agent include but is not limited to starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose,
Or mixtures thereof one of croscarmellose sodium and crospovidone；The lubricant includes but is not limited to talcum
Or mixtures thereof one of powder, stearic acid, rilanit special and polyethylene glycol.
Second aspect, the present invention provide a kind of Misoprostol tablet, include as follows in every 10,000 misoprostol tablets by LC-MS
Component:
Wherein, the average grain diameter (D50) of the microcrystalline cellulose 1 is 50-90 μm, the average grain diameter of microcrystalline cellulose 2
It (D50) is 160-180 μm.
The third aspect, the present invention provide a kind of Misoprostol tablet, include as follows in every 10,000 misoprostol tablets by LC-MS
Component:
Wherein, the average grain diameter (D50) of the microcrystalline cellulose 1 is 50-90 μm, the average grain diameter of microcrystalline cellulose 2
It (D50) is 160-180 μm.
Fourth aspect, the present invention provide a kind of Misoprostol tablet, include as follows in every 10,000 misoprostol tablets by LC-MS
Component:
Wherein, the average grain diameter (D50) of the microcrystalline cellulose 1 is 50-90 μm, the average grain diameter of microcrystalline cellulose 2
It (D50) is 160-180 μm.
5th aspect, the present invention provide a kind of purposes of Misoprostol composition, will be any described in first aspect
Misoprostol composition with mifepristone is sequential merges, for terminating the early pregnancy in menopause 49 days.
In addition, the present invention also provides a kind of preparation methods of Misoprostol composition, comprising the following steps:
1) Misoprostol hypromellose compound and disintegrating agent are uniformly mixed；
2) the lesser microcrystalline cellulose 1 of partial size is added in above-mentioned material and is uniformly mixed；
3) the biggish microcrystalline cellulose 2 of partial size is added in above-mentioned material and is uniformly mixed；
4) rilanit special is added in above-mentioned material and is uniformly mixed, obtain total mix particle；
5) above-mentioned total mix particle is placed in tabletting in high speed rotary tablet press.
Further, misoprostol tablets by LC-MS made from composition scheme of the invention and preparation method, specification packet are utilized
Include but be not limited to 0.1mg and 0.2mg, be mainly used for mifepristone it is sequential merge be used in terminate menopause 49 days in morning
Phase gestation.
Compared with prior art, the beneficial effects of the present invention are:
The present invention uses the microcrystalline cellulose of two kinds of different-grain diameters can be with material layering in effective solution tableting processes
Problem, the tablet content uniformity of preparation meet Chinese Pharmacopoeia requirement, and the import of dissolution curve and Britain PHARMACIA production
It is consistent that original grinds medicine；It dissolves out according to Misoprostol tablet produced by the present invention with fater disintegration, the characteristics of uniform content, is suitble to
Industrial production.
Detailed description of the invention
Fig. 1 is the dissolution curve that comparative example grinds medicine in aqueous medium (paddle method, 500ml water, 30 turns) with original；
Fig. 2 is the dissolution curve that embodiment grinds medicine in aqueous medium (paddle method, 500ml water, 30 turns) with original.
Specific embodiment
The present invention will be further explained below with reference to the attached drawings and specific examples.
Comparative example 1
| Component | Dosage |
| Misoprostol hypromellose compound | 200g |
| Microcrystalline cellulose 1 | 352g |
| Microcrystalline cellulose 2 | 1408g |
| Sodium carboxymethyl starch | 30g |
| Rilanit special | 10g |
70 μm of the average grain diameter (D50) of microcrystalline cellulose 1,170 μm of the average grain diameter (D50) of microcrystalline cellulose 2.
Preparation method:
1) Misoprostol hypromellose compound and sodium carboxymethyl starch are uniformly mixed；
2) microcrystalline cellulose 1 is added in above-mentioned material, is uniformly mixed；
3) microcrystalline cellulose 2 is added in above-mentioned material, is uniformly mixed；
4) rilanit special is added to and is uniformly mixed to obtain total mix material in above-mentioned material；
5) above-mentioned material is set into tabletting in high speed tablet press.10,000 are made, the misoprostol tablets by LC-MS that specification is 0.1mg is evaluated
Process:
(1) uniformity of dosage units changes in tableting processes
Three sections before, during and after entire tableting processes are divided into according to the time period, taken before starting at every section in tablet press machine discharge port
Sample, it is uniform according to Chinese Pharmacopoeia four 0941 Content uniformity test (A+2.2S≤15) detection tablet contents of version in 2015
Degree.
(2) dissolution rate
According to dissolution method (Chinese Pharmacopoeia four 0931 dissolution rates of version in 2015 and the second method of drug release determination method).
Comparative example 2
| Component | Dosage |
| Misoprostol hypromellose compound | 200g |
| Microcrystalline cellulose 1 | 978g |
| Microcrystalline cellulose 2 | 782g |
| Sodium carboxymethyl starch | 30g |
| Rilanit special | 10g |
51 μm of the average grain diameter (D50) of microcrystalline cellulose 1,180 μm of the average grain diameter (D50) of microcrystalline cellulose 2.
Preparation method:
1) Misoprostol hypromellose compound and sodium carboxymethyl starch are uniformly mixed；
2) microcrystalline cellulose 1 is added in above-mentioned material, is uniformly mixed；
3) microcrystalline cellulose 2 is added in above-mentioned material, is uniformly mixed；
4) rilanit special is added to and is uniformly mixed to obtain total mix material in above-mentioned material；
5) above-mentioned material is set into tabletting in high speed tablet press.10,000 are made, the misoprostol tablets by LC-MS that specification is 0.1mg is evaluated
Process and comparative example 1 are consistent.
Comparative example 1, the uniformity of dosage units of comparative example 2 the result is as follows:
Comparative example dissolution curve comparing result is as shown in Fig. 1.
The result shows that:
When using the ratio of microcrystalline cellulose 2 and microcrystalline cellulose 1 to be layered in preparation process for the formula tabletting of 4:1
Phenomenon, the obtained misoprostol tablets by LC-MS uniformity is unqualified, but with original to grind medicine consistent for dissolution curve.
When using the ratio of microcrystalline cellulose 2 and microcrystalline cellulose 1 not to be layered, obtain for the formula tabletting of 0.8:1
The misoprostol tablets by LC-MS uniformity is qualified, but to grind medicine with original inconsistent for dissolution curve.
Embodiment 1
| Component | Dosage |
| Misoprostol hypromellose compound | 200g |
| Microcrystalline cellulose 1 | 400g |
| Microcrystalline cellulose 2 | 1360g |
| Sodium carboxymethyl starch | 30g |
| Rilanit special | 10g |
51 μm of the average grain diameter (D50) of microcrystalline cellulose 1,180 μm of the average grain diameter (D50) of microcrystalline cellulose 2.
Preparation method is the same as comparative example 1
Evaluation procedure
Uniformity of dosage units and dissolution rate sampling and detection process are the same as comparative example 1.
Embodiment 2
70 μm of the average grain diameter (D50) of microcrystalline cellulose 1,170 μm of the average grain diameter (D50) of microcrystalline cellulose 2.
Preparation method, uniformity of dosage units and dissolution rate sampling and detection process are same as Example 1.
Embodiment 3
| Component | Dosage |
| Misoprostol hypromellose compound | 200g |
| Microcrystalline cellulose 1 | 820g |
| Microcrystalline cellulose 2 | 940g |
| Sodium carboxymethyl starch | 30g |
| Rilanit special | 10g |
61 μm of the average grain diameter (D50) of microcrystalline cellulose 1,180 μm of the average grain diameter (D50) of microcrystalline cellulose 2.
Preparation method, uniformity of dosage units and dissolution rate sampling and detection process are same as Example 1.
Embodiment 4
| Component | Dosage |
| Misoprostol hypromellose compound | 200g |
| Microcrystalline cellulose 1 | 820g |
| Microcrystalline cellulose 2 | 940g |
| Sodium carboxymethyl starch | 30g |
| Rilanit special | 10g |
89 μm of the average grain diameter (D50) of microcrystalline cellulose 1,163 μm of the average grain diameter (D50) of microcrystalline cellulose 2.
Preparation method, uniformity of dosage units and dissolution rate sampling and detection process are same as Example 1.
The uniformity of dosage units of embodiment 1,2,3 and 4 the result is as follows:
The dissolution curve comparing result of embodiment 1,2,3 and 4 is as shown in Fig. 2.
The result shows that: preparation method according to the invention can be solved effectively using the cellulose formulation of two kinds of grain size specifications
The certainly lamination problem in tableting processes, through detecting, and 1,2,3,4 uniformity of embodiment meets standards of pharmacopoeia, the group of three kinds of formulas
It is almost the same that dissolution curve grinds medicine with original.
Taking the above-mentioned ideal embodiment according to the present invention as inspiration, through the above description, relevant staff is complete
Various changes and amendments can be carried out without departing from the scope of the technological thought of the present invention' entirely.The technology of this invention
Property range is not limited to the contents of the specification, it is necessary to which the technical scope thereof is determined according to the scope of the claim.
Claims (7)
1. Misoprostol composition, which is characterized in that include following component:
Wherein, Misoprostol content is 1% in the Misoprostol hypromellose compound, and the crystallite is fine
Tieing up plain 1 average grain diameter (D50) is 50-90 μm, and 2 average grain diameter of microcrystalline cellulose (D50) is 160-180 μm.
2. Misoprostol composition according to claim 1, which is characterized in that the Misoprostol hydroxypropyl is fine
The average grain diameter (D50) for tieing up plain compound is 50-200 μm.
3. Misoprostol composition according to claim 1, which is characterized in that the microcrystalline cellulose 2 and crystallite are fine
The mass ratio of dimension element 1 is in 3.4:1-1:1.
4. Misoprostol composition according to claim 1, which is characterized in that the disintegrating agent includes but is not limited to form sediment
One of powder, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, croscarmellose sodium and crospovidone or its
Mixture；The lubricant includes but is not limited to one of talcum powder, stearic acid, rilanit special and polyethylene glycol or it is mixed
Close object.
5. Misoprostol tablet, which is characterized in that include following component in every 10,000 misoprostol tablets by LC-MS:
Wherein, the average grain diameter (D50) of the microcrystalline cellulose 1 is 50-90 μm, and the average grain diameter (D50) of microcrystalline cellulose 2 is
160-180μm。
6. Misoprostol tablet, which is characterized in that include following component in every 10,000 misoprostol tablets by LC-MS:
Wherein, the average grain diameter (D50) of the microcrystalline cellulose 1 is 50-90 μm, and the average grain diameter (D50) of microcrystalline cellulose 2 is
160-180μm。
7. Misoprostol tablet, which is characterized in that include following component in every 10,000 misoprostol tablets by LC-MS:
Wherein, the average grain diameter (D50) of the microcrystalline cellulose 1 is 50-90 μm, and the average grain diameter (D50) of microcrystalline cellulose 2 is
160-180μm。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810396645.XA CN108434110B (en) | 2018-04-28 | 2018-04-28 | Misoprostol composition, tablet and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810396645.XA CN108434110B (en) | 2018-04-28 | 2018-04-28 | Misoprostol composition, tablet and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108434110A CN108434110A (en) | 2018-08-24 |
| CN108434110B true CN108434110B (en) | 2019-09-10 |
Family
ID=63201856
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810396645.XA Active CN108434110B (en) | 2018-04-28 | 2018-04-28 | Misoprostol composition, tablet and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108434110B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1473561A (en) * | 2003-06-27 | 2004-02-11 | 辉 刘 | Quick-releasing talbet in vagina and its preparing method |
| CN102697746A (en) * | 2012-06-11 | 2012-10-03 | 广州朗圣药业有限公司 | Rapid melting misoprostol vaginal composition as well as preparation method and application of same |
| CN104510718A (en) * | 2013-09-27 | 2015-04-15 | 天津孚音生物科技发展有限公司 | Misoprostol solid composition capable of being stored at room temperature and used for vagina, and preparation method thereof |
| WO2016004960A2 (en) * | 2014-07-11 | 2016-01-14 | Azanta A/S | Misoprostol dispersible tablet |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007035954A2 (en) * | 2005-09-23 | 2007-03-29 | Duramed Pharmaceuticals, Inc. | Vaginal tablets comprising misoprostol and methods of making and using the same |
-
2018
- 2018-04-28 CN CN201810396645.XA patent/CN108434110B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1473561A (en) * | 2003-06-27 | 2004-02-11 | 辉 刘 | Quick-releasing talbet in vagina and its preparing method |
| CN102697746A (en) * | 2012-06-11 | 2012-10-03 | 广州朗圣药业有限公司 | Rapid melting misoprostol vaginal composition as well as preparation method and application of same |
| CN104510718A (en) * | 2013-09-27 | 2015-04-15 | 天津孚音生物科技发展有限公司 | Misoprostol solid composition capable of being stored at room temperature and used for vagina, and preparation method thereof |
| WO2016004960A2 (en) * | 2014-07-11 | 2016-01-14 | Azanta A/S | Misoprostol dispersible tablet |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108434110A (en) | 2018-08-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2777696B1 (en) | Preparation of stable pharmaceutical dosage forms | |
| CN102631347B (en) | Gefinitib medicinal composite and method for preparing same | |
| JPS62149632A (en) | Solid medicine | |
| JP2009079034A (en) | New niacin controlled-release-type preparation | |
| CN106389360A (en) | Directly-compressed tablet of dapoxetine hydrochloride and preparation method thereof | |
| CN105078915A (en) | Rivaroxaban tablets and preparation method for same | |
| CN105581990A (en) | Ambrisentan tablet and preparation method thereof | |
| CN109875972B (en) | Olmesartan medoxomil and amlodipine pharmaceutical composition | |
| CN112494440A (en) | Sitagliptin phosphate tablet and preparation method thereof | |
| CN106309388A (en) | Medicine composition for treating congestive heart failure and preparation method thereof | |
| CN105434386B (en) | A kind of sustained-release tablet containing highly-water-soluble active constituent and preparation method thereof | |
| ZA200607156B (en) | Sustained release pharmaceutical composition of indapamide | |
| CN108434110B (en) | Misoprostol composition, tablet and application thereof | |
| CN107669645A (en) | The preparation method of ciprofloxacin hydrocloride tablets | |
| CN104434829B (en) | A kind of Essential Oil of Acorus tatarinowii oral quick disintegrating tablet and preparation method thereof | |
| WO2022222886A1 (en) | Elagolix sodium composition | |
| CN102198107B (en) | Lacidipine dispersible tablets and preparation method thereof | |
| CN103989643B (en) | Tablet containing ramelteon and copolyvidone | |
| CN102283816B (en) | Silodosin sustained-release tablet and preparation method thereof | |
| CN101491493A (en) | Ferulic acid piperazine slow-release medicine preparation | |
| JP4370050B2 (en) | Clarithromycin tablets and method for producing the same | |
| RU2007147953A (en) | PHARMACEUTICAL RECIPES OF MICRONIZED (4-CHLOROPHENYL) [4- (4-pyridylmethyl) -phthalazin-1-yl] AND ITS SALTS WITH IMMEDIATE EXCESSION AND HIGH CONTENT | |
| CN107375938B (en) | Glucosamine hydrochloride adhesive, tablets and preparation method thereof | |
| CN102058552B (en) | Sofalcone sustained release tablet and preparation method thereof | |
| CN104337783B (en) | A kind of capecitabine tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |