CN103610657A - Acotiamide sustained-release preparation - Google Patents
Acotiamide sustained-release preparation Download PDFInfo
- Publication number
- CN103610657A CN103610657A CN201310581924.0A CN201310581924A CN103610657A CN 103610657 A CN103610657 A CN 103610657A CN 201310581924 A CN201310581924 A CN 201310581924A CN 103610657 A CN103610657 A CN 103610657A
- Authority
- CN
- China
- Prior art keywords
- examining
- amine
- slow
- slow releasing
- preparation
- 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
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides an acotiamide sustained-release preparation. An acotiamide sustained-release part contains at least one high molecular polymer which is a sustained-release framework material, preferably hydroxypropyl methyl cellulose, methyl cellulose, hydroxypropyl cellulose, polyethylene oxide, hydroxyethyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone, acrylic acid copolymer and the like.
Description
Technical field
The present invention relates to field of medicaments, relate in particular to a kind of Ah examining for amine slow releasing preparation.
Background technology
Ah examining, for amine (Acotiamide Hydrochloride), belongs to aminothiazole derivs,
Ah examining is two (1-Methylethyl) amino of N-{2-[for amination formal name used at school] ethyl }-2-[(2-hydroxyl-4,5-dimethoxy benzoyl) amino] thiazole-4-carboxamide hydrochlorate.English chemical name: 2-[Bis (1-methylethyl) amino] ethyl}-2-[(2-hydroxy-4,5-dimethoxybenzoy) amino] thiazo le-4-carboxamide monohydrochlor ide; Molecular formula: C
21h
30n40
5s HCl 3H
2o; Molecular weight: 541.06; CAS registration number: 773092-05-0, be by day intrinsic safety Si Telaisi drugmaker in Zeria Pharmaceuticals Co., functional dyspepsia (FD) medicine for treatment that Ltd (Ze Li new drug Co., Ltd.) develops jointly, commodity are called Acofide, on June 3rd, 2013, take the lead in going on the market in Japan.
Existing Ah examining is three times on the one for amine preparation usage and dosage, each 100mg.Ah examining only has 13.31 ± 6.91 hours for the half-life of amine.Blood drug level just declined to a great extent at 5 hours, for maintaining drug effect, will maintain blood concentration, will increase and take number of times, thereby must take medicine every day 3 times.This is to often going on business or often having the patient of commercial affairs dinner party to be relatively difficult to adapt to.
Summary of the invention
The object of the present invention is to provide a kind of Ah examining for amine slow releasing preparation, another object of the present invention is to provide corresponding Ah examining for the preparation method of amine slow releasing preparation.
The invention provides a kind of Ah examining for amine slow releasing preparation, comprise slow releasing tablet, the dosage forms such as slow releasing capsule.
The invention provides a kind of Ah examining for amine slow releasing preparation, it is sustained-release matrix material that Ah examining contained at least one high molecular polymer for amine slow-released part, preferably hypromellose, methylcellulose, hydroxypropyl cellulose, polyoxyethylene, hydroxyethyl-cellulose, polyvinyl alcohol, polyvinylpyrrolidone, acrylic copolymer etc.;
Slow releasing preparation of the present invention preferably a small amount of micropowder silica gel is made fluidizer;
Ah examining of the present invention contained a small amount of lubricant for amine slow releasing preparation, preferably magnesium stearate, calcium stearate or stearic acid.
The invention provides a kind of Ah examining for the preparation method of amine slow releasing preparation, comprise the steps:
Preparation technology can be: principal agent and adjuvant are crossed respectively to 100 mesh sieves.By the principal agent in slow-released part and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol soft material processed, 16 orders are granulated, and 50 ℃ dry, and 16 order granulate, add magnesium stearate as slow-released part granule; On tablet machine, prepare this Ah examining for the slow releasing tablet of amine.
Preparation technology can be: principal agent and adjuvant are crossed respectively to 100 mesh sieves.By the principal agent in slow-released part and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol, as binding agent, with extruding rolling circle equipment, prepare slow-release micro-pill; By the principal agent in immediate release section and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol, as binding agent, with extruding rolling circle equipment, prepare slow-release micro-pill; By two kinds of micropills difference film coatings, after mixing, incapsulate.
The invention provides a kind of Ah examining for amine slow releasing preparation:
The invention provides a kind of Ah examining for amine slow releasing preparation:
The invention provides a kind of Ah examining for amine slow releasing preparation:
The invention provides a kind of Ah examining for amine slow releasing preparation:
The invention provides a kind of Ah examining for amine slow releasing preparation:
Ah examining of the present invention, for the preparation method of amine slow releasing preparation, comprises the steps:
Preparation technology can be: principal agent and adjuvant are crossed respectively to 100 mesh sieves.By the principal agent in slow-released part and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol soft material processed, 16 orders are granulated, and 50 ℃ dry, and 16 order granulate, add magnesium stearate as slow-released part granule; On tablet machine, prepare this Ah examining for the slow releasing tablet of amine.
Preparation technology can be: principal agent and adjuvant are crossed respectively to 100 mesh sieves.By the principal agent in slow-released part and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol, as binding agent, with extruding rolling circle equipment, prepare slow-release micro-pill; By the principal agent in immediate release section and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol, as binding agent, with extruding rolling circle equipment, prepare slow-release micro-pill; By two kinds of micropills difference film coatings, after mixing, incapsulate.
Ah examining provided by the invention is for amine slow releasing tablet system formula and preparation method thereof, make an oral slow-releasing preparation product, make Ah examining for amine after oral, in body system, slowly discharge, maintain blood drug level, thereby make to take every day a deuterzooid slow releasing preparation product, can maintain the blood drug level of one day.
Embodiment:
Embodiment 1: Ah examining is for the preparation of amine slow releasing tablet
Preparation technology: principal agent and adjuvant are crossed respectively to 100 mesh sieves.By the principal agent in immediate release section and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol soft material processed, 16 orders are granulated, and 60 ℃ dry, and 16 order granulate, add magnesium stearate as immediate release section granule; By the principal agent in slow-released part and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol soft material processed, 16 orders are granulated, and 50 ℃ dry, and 16 order granulate, add magnesium stearate as slow-released part granule; In bi-layer tablet press, prepare this Ah examining for the double-layer sustained release tablets of amine.
Embodiment 2: Ah examining is for the preparation of amine slow releasing tablet
Preparation technology: principal agent and adjuvant are crossed respectively to 100 mesh sieves.By the principal agent in slow-released part and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol soft material processed, 16 orders are granulated, and 50 ℃ dry, and 16 order granulate, add magnesium stearate tabletting as slow-released part; Hypromellose in immediate release section is made into 5% aqueous solution, principal agent is added and make its suspendible even, utilize coating equipment in sugar production line that immediate release section is wrapped on slow-released part.
Embodiment 3: Ah examining is for the preparation of amine slow releasing tablet
Preparation technology: principal agent and adjuvant are crossed respectively to 100 mesh sieves.By the principal agent in slow-released part and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol soft material processed, 16 orders are granulated, and 50 ℃ dry, and 16 order granulate, add magnesium stearate tabletting as slow-released part; Hypromellose in immediate release section is made into 5% aqueous solution, principal agent is added and make its suspendible even, utilize coating equipment in sugar production line that immediate release section is wrapped on slow-released part.
Embodiment 4: Ah examining is for the preparation of amine slow releasing tablet
Preparation technology: principal agent and adjuvant are crossed respectively to 100 mesh sieves.By the principal agent in slow-released part and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol soft material processed, 16 orders are granulated, and 50 ℃ dry, and 16 order granulate, add magnesium stearate tabletting as slow-released part; Hypromellose in immediate release section is made into 5% aqueous solution, principal agent is added and make its suspendible even, utilize coating equipment in sugar production line that immediate release section is wrapped on slow-released part.
Embodiment 5: Ah examining is for the preparation of amine slow releasing capsule
Preparation technology can be: principal agent and adjuvant are crossed respectively to 100 mesh sieves.By the principal agent in slow-released part and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol, as binding agent, with extruding rolling circle equipment, prepare slow-release micro-pill; By the principal agent in immediate release section and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol, as binding agent, with extruding rolling circle equipment, prepare slow-release micro-pill; By two kinds of micropills difference film coatings, after mixing, incapsulate.
Embodiment 6:
Mensuration Ah examining be the approximate solubility in different medium for amine, as follows.
With reference to 2010 editions approximate solubility assay methods of Chinese Pharmacopoeia: add excessive Ah examining for amine in each medium of the test tubes of 10 milliliters, under 25 ℃ of conditions every 5 minutes, on turn 200/shaking table per minute, jolting test tube was 30 seconds.After 30 minutes, with 0.25 μ m filtering with microporous membrane, in HPLC mensuration subsequent filtrate, Ah examining is for amine concentration.
Ah examining be the approximate solubility in different medium for amine
| Medium | Approximate solubility (mg/ml) |
| 0.1M hydrochloric acid | 0.18 |
| PH4.8 acetate buffer | 17.21 |
| Water | 5.93 |
| PH6.8 phosphate buffer | 2.71 |
From the above results, Ah examining is lower for amine dissolubility in 0.1M HC1 medium, cannot meet sink conditions, in pH4.5 acetate buffer, water, pH6.8 phosphate buffer, can meet sink conditions requirement, take pH6.8 phosphate buffer as preferred dissolution medium.
The HPLC analytical method of embodiment 7 products of the present invention
Product of the present invention (comprise and be not restricted to the product of embodiment 1-5), should be 98.0%～102.0% of labelled amount containing Ah examining for amine.
According to high performance liquid chromatography, test, with octyl silane group silica gel, it is filler, with volume ratio 10:20 methanol-phosphate buffer, (get potassium dihydrogen phosphate 4.0g, add after water 1000ml dissolving, with phosphorus acid for adjusting pH value to 5.3) be mobile phase A, take acetonitrile as Mobile phase B, and according to the form below program is carried out gradient elution; Flow velocity is 1.0ml per minute, and detection wavelength is 240nm; Column temperature is 45 ℃.Get need testing solution, get 20 μ l injection liquid chromatographies, record chromatogram, Ah examining is 12.6 minutes for amine peak retention time, and number of theoretical plate calculates and is not less than 2500 for amine peak by Ah examining,
The gradient elution program of related substance
Embodiment 8:
The drug-eluting behavior evaluation condition obtaining in embodiment 1-5 is as follows:
Dissolution medium: pH6.8 phosphate buffer
Dissolution medium volume: 900ml
Dissolving-out method: with reference to 2010 editions dissolution determination methods of Chinese Pharmacopoeia, select dissolution determination the second method (being oar method), rotating speed is 50rpm.
Adopt HPLC method to measure, embodiment 1-5, dissolution there was no significant difference.
Embodiment 9:
Get the prepared tablet samples of embodiment 1-4, under packing (aluminum-plastic packaged, to put in carton) condition, in 40 ℃, relative humidity, place 6 months for 75% time, in the time of 0,0.5,1,2,3,6 month, respectively get 10, measure tablet hardness (kg).The results are shown in Table.
Tablet hardness is investigated result
Accelerated test is investigated 6 months, and hardness measurement result shows, the tablet that embodiment 1-4 makes was placed after 6 months, and hardness all remains unchanged, and has significantly improved the stability of preparation, the requirement that can meet transportation and store.
Embodiment 10: embodiment 1-5 and product quality compared,
From above-mentioned experimental result, adopt embodiment 1-4 technique to prepare Ah examining for amine product, tablet compressibility is good, and product dissolution rate is stable, and under placement condition for a long time, hardness and crystal formation are all stable.
Embodiment 11: on the enterokinesia impact that mouse small intestine wriggles of slowing down
(1) test objective
To the small intestinal peristalsis mouse gavaging active carbon that slows down, the propelling rate of active carbon in small intestinal of take is index, observes embodiment 1, and whether embodiment 5 products promote mouse small intestine to wriggle 0.3, under the dosage of 1mg, 3mg/kg.
(2) content of the test
Get 90 of mices, male and female half and half, 20-22 gram, random packet, minutes 9 groups, wherein 8 groups every gavages 1.5mg/ml raceanisodamine suspension 0.5ml, makes the enterokinesia model that slows down, and another 1 group is blank group, modeling group administration every day 1 time, successive administration 3 days.
Fasting (can't help water) after administration in the 2nd day,
In the 4th day, positive controls gavaged motilium liquid (1mg/ml), and model group and blank group gavage distilled water, and administration volume is 0.4ml/20g.Successive administration 3 days, every day twice, each 1 time sooner or later.
In the 4th day, gavage embodiment 1 product (0.5,1,2mg/ml), gavage embodiment 5 products (0.5,1,2mg/ml), positive controls gavages motilium (1mg/ml), and model group and blank group gavage distilled water, and administration volume is 0.4ml/20g.Successive administration 3 days,, every day 1 time, early 1 time.
In the 7th day, gavage 5% Insta-Char 0.5ml, after 20 minutes, put to death mice, the taking-up intestinal tube of cutting open the belly, measure pylorus to the distance in active carbon forward position as " advance distance in active carbon intestinal ", measure pylorus to the distance of caecum as full intestinal length, be calculated as follows: advance distance (cm) in active carbon propelling rate=active carbon intestinal/full intestinal length (cm) * 100%.Each organizes t check between active carbon propelling rate employing group, carries out statistical procedures.
(3) result of the test:
On the enterokinesia impact that mouse small intestine wriggles of slowing down
Note: administration group with model group than P<0.05, * * P<0.01.
Claims (8)
1. Ah examining, for an amine slow releasing preparation, comprises slow releasing tablet, the dosage forms such as slow releasing capsule.
2. Ah examining is for amine slow releasing preparation, it is sustained-release matrix material that Ah examining contained at least one high molecular polymer for amine slow-released part, preferably hypromellose, methylcellulose, hydroxypropyl cellulose, polyoxyethylene, hydroxyethyl-cellulose, polyvinyl alcohol, polyvinylpyrrolidone, acrylic copolymer etc.;
Slow releasing preparation of the present invention preferably a small amount of micropowder silica gel is made fluidizer;
Ah examining of the present invention contained a small amount of lubricant for amine slow releasing preparation, preferably magnesium stearate, calcium stearate or stearic acid.
3. Ah examining, for a preparation method for amine slow releasing preparation, comprises the steps:
Preparation technology can be: principal agent and adjuvant are crossed respectively to 100 mesh sieves.By the principal agent in slow-released part and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol soft material processed, 16 orders are granulated, and 50 ℃ dry, and 16 order granulate, add magnesium stearate as slow-released part granule; On tablet machine, prepare this Ah examining for the slow releasing tablet of amine.
Preparation technology can be: principal agent and adjuvant are crossed respectively to 100 mesh sieves.By the principal agent in slow-released part and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol, as binding agent, with extruding rolling circle equipment, prepare slow-release micro-pill; By the principal agent in immediate release section and the adjuvant mix homogeneously except magnesium stearate, with 70% ethanol, as binding agent, with extruding rolling circle equipment, prepare slow-release micro-pill; By two kinds of micropills difference film coatings, after mixing, incapsulate.
4. Ah examining is for amine slow releasing preparation:
5. Ah examining is for amine slow releasing preparation:
6. Ah examining is for amine slow releasing preparation:
7. Ah examining is for amine slow releasing preparation:
8. Ah examining is for amine slow releasing preparation:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310581924.0A CN103610657A (en) | 2013-11-20 | 2013-11-20 | Acotiamide sustained-release preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310581924.0A CN103610657A (en) | 2013-11-20 | 2013-11-20 | Acotiamide sustained-release preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103610657A true CN103610657A (en) | 2014-03-05 |
Family
ID=50161392
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310581924.0A Pending CN103610657A (en) | 2013-11-20 | 2013-11-20 | Acotiamide sustained-release preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103610657A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104523686A (en) * | 2014-12-04 | 2015-04-22 | 石家庄四药有限公司 | Acotiamide hydrochloride medicinal preparation and preparation method thereof |
| CN105055363A (en) * | 2015-09-06 | 2015-11-18 | 叶澄 | Acotiamide hydrochloride sustained-release drug and preparation method thereof |
| CN105412026A (en) * | 2014-09-18 | 2016-03-23 | 中美华世通生物医药科技（武汉）有限公司 | Hydrochloric acid acotiamide tablets and preparation method thereof |
| CN105476963A (en) * | 2015-12-17 | 2016-04-13 | 北京科莱博医药开发有限责任公司 | Acotiamide hydrochloride sustained-release pellet and preparation method thereof |
| CN106511291A (en) * | 2016-09-24 | 2017-03-22 | 济南康和医药科技有限公司 | Acotiamide hydrochloride controlled release tablet and preparation method thereof |
| CN106918659A (en) * | 2017-01-22 | 2017-07-04 | 合肥拓锐生物科技有限公司 | About the analysis method of material in a kind of acotiamide hydrochloride hydrate raw material and its preparation |
| CN107228909A (en) * | 2016-03-24 | 2017-10-03 | 中美华世通生物医药科技（武汉）有限公司 | The method in acotiamide hydrochloride hydrate bulk drug and its preparation about material is determined using HPLC |
| CN109999003A (en) * | 2019-05-14 | 2019-07-12 | 湖南华纳大药厂股份有限公司 | Acotiamide hydrochloride hydrate oral disintegrating tablet and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102657629A (en) * | 2012-05-14 | 2012-09-12 | 深圳市华力康生物医药有限公司 | Ticagrelor sustained-release tablet system and preparation method thereof |
-
2013
- 2013-11-20 CN CN201310581924.0A patent/CN103610657A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102657629A (en) * | 2012-05-14 | 2012-09-12 | 深圳市华力康生物医药有限公司 | Ticagrelor sustained-release tablet system and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| MARY L. NOLAN ETAL: "Acotiamide: First Global Approval", 《DRUGS》 * |
| SHIGERU FURUTA ETAL: "LC determination of Z-338, novel gastroprokinetic agent in dog plasma by SCX solid phase extraction", 《JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS》 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105412026A (en) * | 2014-09-18 | 2016-03-23 | 中美华世通生物医药科技（武汉）有限公司 | Hydrochloric acid acotiamide tablets and preparation method thereof |
| CN105412026B (en) * | 2014-09-18 | 2019-01-08 | 中美华世通生物医药科技（武汉）有限公司 | Acotiamide hydrochloride hydrate piece and preparation method thereof |
| CN104523686A (en) * | 2014-12-04 | 2015-04-22 | 石家庄四药有限公司 | Acotiamide hydrochloride medicinal preparation and preparation method thereof |
| CN105055363A (en) * | 2015-09-06 | 2015-11-18 | 叶澄 | Acotiamide hydrochloride sustained-release drug and preparation method thereof |
| CN105476963A (en) * | 2015-12-17 | 2016-04-13 | 北京科莱博医药开发有限责任公司 | Acotiamide hydrochloride sustained-release pellet and preparation method thereof |
| CN107228909A (en) * | 2016-03-24 | 2017-10-03 | 中美华世通生物医药科技（武汉）有限公司 | The method in acotiamide hydrochloride hydrate bulk drug and its preparation about material is determined using HPLC |
| CN107228909B (en) * | 2016-03-24 | 2021-05-28 | 中美华世通生物医药科技(武汉)股份有限公司 | Method for measuring acotiamide hydrochloride raw material medicine and related substances in preparation thereof by using HPLC |
| CN106511291A (en) * | 2016-09-24 | 2017-03-22 | 济南康和医药科技有限公司 | Acotiamide hydrochloride controlled release tablet and preparation method thereof |
| CN106918659A (en) * | 2017-01-22 | 2017-07-04 | 合肥拓锐生物科技有限公司 | About the analysis method of material in a kind of acotiamide hydrochloride hydrate raw material and its preparation |
| CN109999003A (en) * | 2019-05-14 | 2019-07-12 | 湖南华纳大药厂股份有限公司 | Acotiamide hydrochloride hydrate oral disintegrating tablet and preparation method thereof |
| CN109999003B (en) * | 2019-05-14 | 2022-03-25 | 湖南华纳大药厂股份有限公司 | Acotiamide hydrochloride orally disintegrating tablet and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103610657A (en) | Acotiamide sustained-release preparation | |
| CN111405895B (en) | Controlled release pharmaceutical composition and preparation method thereof | |
| US20080014228A1 (en) | Solid form | |
| CN103550190A (en) | Matrix-type controlled release preparation comprising basic substance or salt thereof | |
| MX2010010280A (en) | Extended release forumulation containing a wax. | |
| KR101588259B1 (en) | Formulation of doxylamine and pyridoxine and/or metabolites or salts thereof | |
| RU2011119504A (en) | MEDICINAL DELIVERY SYSTEMS CONTAINING LOW-MAJOR MEDICINES AND ORGANIC ACIDS | |
| US9387166B2 (en) | Controlled release oral dosage form comprising oxycodone | |
| KR100699958B1 (en) | Pharmaceutical compositions containing terbinafin and use thereof | |
| CN111372578A (en) | Amantadine compositions, methods of making and using the same | |
| Fouladi et al. | Preparation and in-vitro evaluation of gastroretentive bupropion hydrochloride tablets | |
| WO2010100657A2 (en) | A novel oral controlled release dosage forms for water soluble drugs | |
| KR20130137595A (en) | Oral controlled release pharmaceutical compositions of blonanserin | |
| CN104523631B (en) | Preparation method of olanzapine orally disintegrating tablet for treating depression | |
| CN102462675A (en) | Bezafibrate sustained release tablet and preparation method thereof | |
| Umamaheswari | Formulation and evaluation of controlled porosity osmotic tablets of lornoxicam | |
| KR102127625B1 (en) | Hydromorphone hydrochloride-containing oral sustained-release pharmaceutical composition | |
| Shahtalebi et al. | Formulation and evaluation of orally disintegrating tablet of ondansetron using natural superdisintegrant | |
| Buwade et al. | Advantages of immediate release tablets over the other tablet forms | |
| JP6272561B2 (en) | Multimodal release formulations of doxylamine and pyridoxine and / or their metabolites or salts | |
| CN111346066A (en) | Sustained release preparation containing piracetam | |
| JP5819680B2 (en) | Small sustained release formulation of ambroxol hydrochloride | |
| US10702479B2 (en) | Pharmaceutical formulation comprising sembragiline | |
| CN113521020B (en) | A solid dosage form of adefovir containing water soluble acid | |
| US20230133326A1 (en) | Stable pharmaceutical compositions of metformin with control on nitroso impurities |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20140305 |
|
| RJ01 | Rejection of invention patent application after publication |