CN102670482A - Sustained release preparation of dronedarone hydrochloride - Google Patents
Sustained release preparation of dronedarone hydrochloride Download PDFInfo
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- CN102670482A CN102670482A CN2012100784166A CN201210078416A CN102670482A CN 102670482 A CN102670482 A CN 102670482A CN 2012100784166 A CN2012100784166 A CN 2012100784166A CN 201210078416 A CN201210078416 A CN 201210078416A CN 102670482 A CN102670482 A CN 102670482A
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Abstract
The invention discloses a sustained release preparation of dronedarone hydrochloride, aiming to maintain an optimal steady state plasma concentration better, improve a pharmaceutical effect and bring convenience for use and reduce hospitalization risk of patients. Active components are released slowly to obtain prospected drug release behavior in vivo and in vitro. Therefore, the sustained release preparation of dronedarone hydrochloride, disclosed by the invention, has the advantages of low drug use time, slow release of drug in vivo, steady plasma concentration, low fluctuation, high bioavailability and high safety.
Description
Technical field
The present invention relates to slow releasing preparation of hydrochloric acid dronedarone and preparation method thereof, belong to field of medicaments.
Background technology
The research and development of slow releasing preparation, the history surplus in the of existing so far 40 year, it is in environment provided, non-lentamente on request constant release, the preparation that medication every day number of times and corresponding ordinary preparation reduce once more at least or prolong to some extent blanking time of medication.This preparation can make human body keep this kind blood drug level to reach the long time; Do not descend quickly the ordinary preparation and do not resemble; Thereby " peak valley " phenomenon that can avoid the ordinary preparation frequent drug administration to be occurred increases safety, effectiveness or the adaptability of medicine, thereby has reduced the medication number of times; Greatly facilitate the patient, particularly the patient of long-term prescription.Peroral dosage form commonly used has matrix tablet, micropore bag pellicle controlled release tablet, laser osmotic pumps, composite particles chamber capsule, label chamber capsule, Entogastric lingering preparation, controlled release suspensoid, drop pill etc.; External preparation has eye with therapy system, oral cavity sticking tablet, transdermal drug delivery system etc.; Injection has water suspension, Emulsion, liposome, microsphere etc.Tablet is with its taking convenience, and preparation technology is simple relatively, and quality is easy to advantage such as control to be become the slow releasing preparation research and development and use the widest, the most sophisticated dosage form of technology.Capsule is also with its taking convenience, and preparation technology is simple relatively, and quality such as is easy to control at advantage becomes a wider dosage form of slow releasing preparation research and development application prospect.Film coating sustained-release and controlled release preparation packs the suitable clothing layer of one deck on the surface of label and piller, it is dissolved under certain condition or be partly dissolved and discharge medicine, can reach the sustained-release and controlled release effect.Its principle belongs to diffusion and discharges, and the energy is based on the osmotic pressure of film intracavity, or the stripping dispersal behavior coated slow release controlled release preparation of drug molecule in polymer is one of type of extensive use in the oral sustained release controlled release preparation.According to its preparation technology's difference, slow releasing preparation can be divided into tablet, capsule, sustained-release dropping pill etc.Used substrate comprises hydrophilic gel sustained-release matrix material, like light propyl cellulose, light propyl methocel, press sodium carboxymethylcellulose pyce, carbomer etc.; Erodible sustained-release matrix material is like stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc.; Water-insoluble sustained-release matrix material is like ethyl cellulose, corn Ruan etc.Along with being on the increase of substrate kind, preparation technology's is ripe day by day perfect, and slow releasing agent is extensive day by day in the application of Chinese-western medicine preparation; Therefore existing medicine is carried out modified form; Produce more medicament slow release dosage form, will greatly enrich drug market, improve quality of medical care.
Arrhythmia is meant rhythm of the heart origin position, cardiac frequency and the rhythm and pace of moving things and conduction of impulse etc., and each is unusual.Press its occurring principle, dividing into impulsion and forming unusual and conduction of impulse unusual two big classes.Pathogenesis can be divided into 2 two kinds: (one) self-disciplining increases, unusual self-disciplining causes unusual that impulsion forms with triggered activity: the scheming cell with self-disciplining causes unsuitable impulsion granting because the excited change of autonomic nervous system or its intrinsic pathological changes increase its self-disciplining.In addition, do not have originally self-disciplining myocardial cell such as atrium, ventricular muscle cell since myocardial ischemia, medicine, electrolyte wadding disorderly, catecholamine the formation that all can cause unusual self-disciplining such as increases.Triggered activity is the after-depolarization that is triggered by normal action potential once and triggers once new action potential and produce the persistence tachyarrhythmia.(2) reciprocal excitation, that conductive impairment causes conduction of impulse is unusual: after excitement spreads out of from the pathway in somewhere; Return the original place from an other pathway again; Making this place that excited phenomenon take place once more and be called reciprocal excitation, is the modal mechanisms of all tachy-arrhythmias.Impulsion is circulation repeatedly in the link of turning back, and produce to continue and arrhythmia fast.
The hydrochloric acid dronedarone is a kind of antiarrhythmic drug; Be applicable to that paroxysmal or persistence atrial fibrillation or room pounce on the patient, currently be sinus rhythm or need the recent generation atrial fibrillation of conversion or the patient that cardiovascular risk factors was pounced on and existed in the room, the cardiovascular diseases that can the reduce above-mentioned patient risk of being in hospital.
The hydrochloric acid dronedarone is short medicine of a biological half-life, and single administration dosage is 400mg, needs 2-3 administration on the one; Make troubles to patient's use; Owing to the influence of factors such as the length of one's sleep, affect the medicine steady plasma-drug concentration, thereby influence drug effect simultaneously.The present invention's technology is a hydrochloric acid dronedarone slow releasing preparation, can be administered once in 24 hours at interval, keeps best steady plasma-drug concentration, improves drug effect, the convenient use.
Summary of the invention
The objective of the invention is better to keep best steady plasma-drug concentration, improve drug effect, reduce patient's the risk of being in hospital.Technical scheme of the present invention is following:
Slow releasing preparation with the hydrochloric acid dronedarone of the present invention.It comprises a kind of delivery system, and delivery system is made up of the label that drug slow is discharged and/or ball core and/or coating, a said active component part or all be present in label and or the ball core in, the remainder of active component is present in the coating.Slow releasing preparation of the present invention in each UD, contains hydrochloric acid dronedarone 200-800mg.
Label of the present invention and/or ball core are by light third methylcellulose; The Sulisi aqueous dispersion; The water solublity coating powder; The ethyl cellulose polyethylene adjoins pyrrolidone; Methylcellulose; Phthalic acid is through propyl methocel; Cellulose acetate-phthalate; Through ethyl cellulose through propyl cellulose; Admire methylcellulose; Sodium carboxymethylcellulose; Cellulose acetate; Cellulose diacetate; Triafol T; Light methylcellulose; The low footpath propyl cellulose that replaces; The crosslinked sodium carboxymethylcellulose pyce of dredging; Wych-elm acid glycerol vinegar; Glycerol monostearate is cruel; Stearic acid; Cohune is put wax; Polyvinyl alcohol; Gather phthalic acid vinyl acetate vinegar; Polystyrene; Gather by ethylene; Polrvinyl chloride; Octadecanol; The phthalic acid diethyl is cruel; Phthalic acid two is hot cruel; Polyethylene Glycol; Sodium alginate; Chitosan; Gelatin; Lac; Pectin; Guar gum; Sucrose; Lactose; Starch; Dextrin; Icing Sugar; Cross linked polyvinyl pyrrolidone; Mannitol; Microcrystalline Cellulose; Pregelatinized Starch; During titanium dioxide is admired one or more are processed; During described coating is compared by ethyl cellulose, starch, Aquacoat, acrylic resin, Opadry, Su Li one or more are processed.
During coating of the present invention is compared by ethyl cellulose, starch, Aquacoat, acrylic resin, Opadry, Su Li one or more are processed.
Lubricant of the present invention is magnesium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, polyethylene glycols, month hang in the pure magnesium sulfate one or more processes.
The release characteristic of hydrochloric acid dronedarone is in the preparation of the present invention: 2h:10-30%, and 6h:25-50%, 12h:40-70% is more than the 24h:85%.
Preparation of the present invention is tablet, granule, pill, capsule or suspensoid.
Through the method for preparing of following slow releasing tablet provided by the present invention, can further understand the present invention, but following description not to qualification of the present invention:
The method for preparing of slow releasing tablet: with the medicine is primary raw material, according to certain ratio, adds medicament slow release framework material and additional materials as substrate, is prepared from through specific technology, apparatus processing again.
Prescription: medicine+substrate.Medicine: hydrochloric acid dronedarone; Substrate: hydrophilic gel medicament slow release framework material, like light propyl cellulose, through propyl methocel, sodium carboxymethylcellulose, carbomer etc.; Erodible medicament slow release framework material is like stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc.; Water-insoluble drug sustained-release matrix material is like ethyl cellulose, corn Ruan's etc. one or more composition and additional materials.
Preparation technology, the practical implementation step is following:
Method one: according to certain ratio with medicine, erodible sustained-release matrix material; Like stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc. and hydrophilic gel sustained-release matrix material; Like light propyl cellulose, light propyl methocel, by sodium carboxymethylcellulose pyce, carbomer etc. and the additives mix homogeneously of milling; Direct compression or dry granulation behind the adding lubricant, tabletting or elder generation add typical binders granulation, drying behind the adding lubricant, add the lubricant tabletting again.
Method two: according to certain ratio with medicine, erodible sustained-release matrix material; After, hexadecanol liquor-saturated like tristearin, octadecanol, Polyethylene Glycol etc. and additives are milled jointly and are mixed; Again with hydrophilic gel sustained-release matrix material, like mixing such as light propyl cellulose, light propyl methocel, crafty sodium carboxymethylcellulose pyce, carbomer, direct compression or dry granulation behind the adding lubricant; Tabletting or elder generation add typical binders granulation, drying behind the adding lubricant, add the lubricant tabletting again.
Method three: according to certain ratio with medicine, additives and water-insoluble sustained-release matrix material; Alcoholic solution mix homogeneously like ethyl cellulose, corn Ruan etc.; Add hydrophilic gel sustained-release matrix material, like light propyl cellulose, through propyl methocel, connect mixing granulations such as sodium carboxymethylcellulose pyce, carbomer, drying; Add lubricant, tabletting.
Method four: according to certain ratio with water-soluble components in medicine, the said additives and water-insoluble sustained-release matrix material; Alcoholic solution mix homogeneously or the dissolving dirty etc. like ethyl cellulose, corn; Vacuum drying is pulverized, and adds hydrophilic gel sustained-release matrix material; As through mixing such as propyl cellulose, light propyl methocel, sodium carboxymethylcellulose, carbomers, add the lubricated tabletting of stining together behind adding lubricant direct compression or the dry granulation again.
Method five:, even with additives and mix lubricant according to certain ratio like ethyl cellulose, corn Ruan etc. with medicine, water-insoluble sustained-release matrix material, tabletting.
The method for preparing of slow releasing capsule: with the medicine is primary raw material, according to certain ratio, adds medicament slow release framework material and additional materials as substrate, is prepared from through specific technology, apparatus processing again.
Prescription: medicine ten substrate.Medicine: hydrochloric acid dronedarone; Substrate: hydrophilic gel medicament slow release framework material, like light propyl cellulose, through propyl methocel, sodium carboxymethylcellulose, carbomer etc.; Erodible medicament slow release framework material is like stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc.; Water-insoluble drug sustained-release matrix material is like ethyl cellulose, corn Ruan's etc. one or more composition and additional materials.
Preparation technology, the practical implementation step is following:
Method one: according to certain ratio with medicine, erodible sustained-release matrix material; Like stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc. and hydrophilic gel sustained-release matrix material; As through propyl cellulose, through propyl methocel, sodium carboxymethylcellulose, carbomer etc. and the additives mix homogeneously of milling; Dry method or wet method are processed slow-release pill or granule, add or do not add additives, be packed in the hard capsule.
Method two: according to certain ratio with medicine and additives mill jointly mix after; Process slow-release pill or granule with dry method or wet method; Reuse erodible sustained-release matrix material is like stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc. and/or hydrophilic gel sustained-release matrix material, as being that coating material is to ball pericardium clothing through solution such as propyl cellulose, light propyl methocel, sodium carboxymethylcellulose, carbomers; Add or do not add additives, be packed in the hard capsule.
Method three: according to certain ratio with medicine, erodible sustained-release matrix material; Like stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc. and hydrophilic gel sustained-release matrix material; As through propyl cellulose, through propyl methocel, sodium carboxymethylcellulose, carbomer etc. and the additives mix homogeneously of milling; Dry method or wet method are processed slow-release pill or granule; Reuse erodible sustained-release matrix material like stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc. and/or hydrophilic gel sustained-release matrix material, is that coating material is to ball pericardium clothing like solution such as light propyl cellulose, light propyl methocel, sodium carboxymethylcellulose, carbomers; Add or do not add additives, be packed in the hard capsule
Method four: according to certain ratio with water-soluble components in medicine, the said additives and water-insoluble sustained-release matrix material, like ethyl cellulose, corn Ruan's etc. alcoholic solution mix homogeneously or dissolving, vacuum drying; Pulverize; Add hydrophilic gel sustained-release matrix material, like light propyl cellulose, through mixing such as propyl methocel, short sodium carboxymethylcellulose pyce, carbomers, dry method or wet method are processed slow-release pill or granule; Add or do not add additives, be packed in the hard capsule.
Method five: according to certain ratio with water-soluble components in medicine, the said additives and water-insoluble sustained-release matrix material; Like ethyl cellulose, corn Ruan's etc. alcoholic solution mix homogeneously or dissolving, vacuum drying is pulverized; Add hydrophilic gel sustained-release matrix material; As through propyl cellulose, through mixing such as propyl methocel, sodium carboxymethylcellulose, carbomers, dry method or wet method are processed slow-release pill or granule, reuse erodible sustained-release matrix material; Like stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc. and/or hydrophilic gel sustained-release matrix material; As light propyl cellulose, light propyl methocel, connect solution such as sodium carboxymethylcellulose pyce, carbomer be coating material to ball pericardium clothing, add or do not add additives, be packed in the hard capsule.
Active component is slow release release in the slow releasing preparation of the present invention, obtains desired drug release behavior in vivo and in vitro.Therefore this preparation has the advantages that the medication number of times is few, medicine delays casual release in vivo, blood drug level is steady, fluctuation is little, bioavailability is high, safe.
The specific embodiment
Through following examples to of the present invention be that the slow releasing preparation of active component is done further and specified with the hydrochloric acid dronedarone, but not as limitation of the present invention.
Prescription
Method for preparing
(1) particulate preparation: hydroxypropyl methylcellulose, microcrystalline Cellulose, sieve mix homogeneously respectively.Add the hydrochloric acid dronedarone again, fully mixing is a binding agent system soft material with 5% 30 POVIDONE K 30 BP/USP 3O aqueous solution, 20 mesh sieve system wet granulars, and 50 ℃ of dryings, 18 mesh sieve granulate, subsequent use.
(2) preparation of coating solution: Opadry is added in the pure water, and add pure water, stirred 1 hour to 100ml, subsequent use.
(3) get (1) granule and carry out coating, obtain coated granule.
(4) in (3) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting promptly gets tablet.
(5) in (1) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting is got (2) coating solution, is wrapped in outside the tablet, gets final product coated tablet.
(6) get (3) gained particle packing in the hungry area softgel shell, promptly get capsule.
The release characteristic of active component is as shown in table 1 in the different dosage form of gained.
The release characteristic of active component in table 1 different dosage form
Claims (6)
1. one kind is the slow releasing preparation of active component with the hydrochloric acid dronedarone.It comprises a kind of delivery system; It is characterized in that: described delivery system is made up of the label that drug slow is discharged and/or ball core and/or coating; A said active component part or all be present in label with or the ball core in, the remainder of active component is present in the coating.
2. slow releasing preparation according to claim 1 is characterized in that: the hydrochloric acid dronedarone is slow release and discharges.
3. slow releasing preparation according to claim 1 is characterized in that: contain hydrochloric acid dronedarone 200-800mg in each dosage unit.
4. according to the described compound slow release preparation of claim 1-3, it is characterized in that: described label and/or ball core by light third methylcellulose, Sulisi aqueous dispersion, water solublity coating powder,, the ethyl cellulose polyethylene adjoin pyrrolidone, methylcellulose, phthalic acid through propyl methocel, cellulose acetate-phthalate,, through ethyl cellulose through propyl cellulose, admire methylcellulose, sodium carboxymethylcellulose, cellulose acetate, cellulose diacetate, Triafol T, light methylcellulose, lowly replace the footpath propyl cellulose, crosslinkedly dredge that sodium carboxymethylcellulose pyce, wych-elm acid glycerol vinegar, glycerol monostearate are cruel, stearic acid, cohune are put wax, polyvinyl alcohol, gather phthalic acid vinyl acetate vinegar, polystyrene, gather in admiring one or more of hot cruel, the Polyethylene Glycol of, phthalic acid cruel by ethylene, polrvinyl chloride, octadecanol, phthalic acid diethyl two, sodium alginate, chitosan, gelatin, Lac, pectin, guar gum, sucrose, lactose, starch, dextrin, Icing Sugar, cross linked polyvinyl pyrrolidone, mannitol, microcrystalline Cellulose, pregelatinized Starch, titanium dioxide and process; During described coating is compared by ethyl cellulose, starch, Aquacoat, acrylic resin, Opadry, Su Li one or more are processed; Said preparation contains lubricant, and said lubricant is magnesium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, polyethylene glycols, month hang in the pure magnesium sulfate one or more processes.
5. according to the described compound slow release preparation of claim 1-4, it is characterized in that: the release characteristic of hydrochloric acid dronedarone is: 2h:10-30%, and 6h:25-50%, 12h:40-70% is more than the 24h:85%.
6. according to the described slow releasing preparation of claim 1-5, it is characterized in that: said preparation is tablet, granule, pill, capsule or suspensoid.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2012100784166A CN102670482A (en) | 2012-03-22 | 2012-03-22 | Sustained release preparation of dronedarone hydrochloride |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2012100784166A CN102670482A (en) | 2012-03-22 | 2012-03-22 | Sustained release preparation of dronedarone hydrochloride |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105997935A (en) * | 2016-05-25 | 2016-10-12 | 齐鲁工业大学 | Dronedarone hydrochloride film-controlled sustained release pellet and preparation process thereof |
| CN107184561A (en) * | 2017-06-01 | 2017-09-22 | 四川制药制剂有限公司 | The production technology of dronedarone hydrochloride piece |
| CN108014082A (en) * | 2017-12-19 | 2018-05-11 | 佛山市弘泰药物研发有限公司 | A kind of dronedarone hydrochloride sustained release tablets and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012023024A2 (en) * | 2010-08-17 | 2012-02-23 | Lupin Limited | Controlled release formulations of dronedarone |
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2012
- 2012-03-22 CN CN2012100784166A patent/CN102670482A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012023024A2 (en) * | 2010-08-17 | 2012-02-23 | Lupin Limited | Controlled release formulations of dronedarone |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105997935A (en) * | 2016-05-25 | 2016-10-12 | 齐鲁工业大学 | Dronedarone hydrochloride film-controlled sustained release pellet and preparation process thereof |
| CN107184561A (en) * | 2017-06-01 | 2017-09-22 | 四川制药制剂有限公司 | The production technology of dronedarone hydrochloride piece |
| CN108014082A (en) * | 2017-12-19 | 2018-05-11 | 佛山市弘泰药物研发有限公司 | A kind of dronedarone hydrochloride sustained release tablets and preparation method thereof |
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Application publication date: 20120919 |