CN102784117A - Gentamicin sulfate composition freeze-dried orally disintegrating tablet and preparation method thereof - Google Patents
Gentamicin sulfate composition freeze-dried orally disintegrating tablet and preparation method thereof Download PDFInfo
- Publication number
- CN102784117A CN102784117A CN2012103007075A CN201210300707A CN102784117A CN 102784117 A CN102784117 A CN 102784117A CN 2012103007075 A CN2012103007075 A CN 2012103007075A CN 201210300707 A CN201210300707 A CN 201210300707A CN 102784117 A CN102784117 A CN 102784117A
- Authority
- CN
- China
- Prior art keywords
- gentamycin sulfate
- oral cavity
- drying
- freeze
- cavity disintegration
- 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)
Abstract
The invention provides a gentamicin sulfate composition freeze-dried orally disintegrating tablet and a preparation method thereof, relates to the technical field of medicines and medicine preparation methods, and mainly solves the problem that a gentamicin sulfate preparation in the prior art is poor in curative effect and inapplicable to children and patients having difficulty in swallowing. The gentamicin sulfate composition freeze-dried orally disintegrating tablet is prepared from components including, by weight, 20%-30% of gentamicin sulfate, 30%-60% of mannitol, 1%-3% of gelatin, 0.1%-0.15% of sucralose and 45%-60% of water for injection. The gentamicin sulfate composition freeze-dried orally disintegrating tablet prepared from the components according to the weight percent is simple in preparation process and composition, is applicable to the children and the patients having difficulty in swallowing, and has the advantages of rapidness in disintegration and effectiveness, sufficiency in medicine absorption, convenience in taking, fine taste and avoidance of the first-pass effect of livers.
Description
Technical field:
The present invention relates to the method for preparing technical field of medicine and medicine, relate in particular to a kind of gentamycin sulfate composition freeze-drying oral cavity disintegration tablet and preparation method thereof.
Background technology:
Gentamycin sulfate is white or off-white color crystalline powder; Odorless; Have draw moist.In water, be prone to dissolve, insoluble in ethanol, ether, acetone or chloroform.The pH of gentamycin 4% aqueous solution is 3.5 ~ 5.5.These article 1mg is equivalent to 1000 units.The oral post-absorption of gentamycin seldom; Concentration in gastrointestinal tract is stable and lasting; Mainly discharge with feces, gram-negative bacterias such as escherichia coli, aerobacteria, klebsiella bacillus, proteus mirabilis, some indole Bacillus proteus, bacillus pyocyaneus, some Neisseria, some non-pigment serratia marcecens and shigella dysenteriae are had antibacterial action with prototype.In the gram positive bacteria, staphylococcus aureus is responsive to these article; Streptococcus is to this article drug resistance.Anaerobe, tubercule bacillus, rickettsia, virus and fungus are also to this article drug resistance.In recent years, because the extensive use of these article, Resistant strain increases gradually, and bacillus pyocyaneus, klebsiella bacillus and serratia marcecens, the positive Bacillus proteus of indole are very high to the resistant rate of these article.
The gentamycin sulfate structural formula is following:
The characteristics of the preparation of oral cavity disintegration tablet are: do not need water or only need a small amount of water, also need not to chew, medicine places in the oral cavity, after rapid dissolving of chance saliva or the disintegrate, along with autonomous and involuntary swallowing act entering digestive system absorption back onset of user.Behavior is basic consistent with conventional tablet in the body.Different with sublingual lozenge, onset does not also rely on oral mucosa and absorbs, the novel dosage form of this kind to tumor patient, child, old age, be unable to leave the bed and severely-disabled patient's optimum, and route of administration is provided to swallowing inconvenient patient.
But the gentamycin sulfate dosage form of listing is mainly conventional tablet, capsule, injection at present.Yet regular dosage form such as tablet and capsule etc. are not suitable for the patient of child, gerontal patient and dysphagia to be taken, and makes the patient produce negation to medication, has reduced the compliance of patient's clinical application.
The existing market is existing to utilize freeze-drying to produce in the three big technology of oral cavity disintegration tablet, and the Zydis method only is applicable to poorly water soluble drugs, and settled problem takes place in the microgranule conference; Lyoc method complex process, with high costs; QuickSolv method and being only applicable to is insoluble to the ingredient of extracting solvent.The disintegration rate that the oral cavity disintegration tablet of prior art for preparing all exists problem slowly.
So still lack at present and press for a kind of like this gentamycin sulfate preparation, its preparation technology is simple, component is simple.The oral absorption rate is high, and taking convenience, delicious is specially adapted to child, old age, is unable to leave the bed, the severely-disabled patient, and to swallowing inconvenient patient's medication.
Summary of the invention:
Technical problem to be solved by this invention is to provide a kind of composition simple, easily manufactured, rapid-action gentamycin sulfate compositions and contain gentamycin sulfate composition freeze-drying oral cavity disintegration tablet that above-mentioned composition processes and preparation method thereof.
Technical problem to be solved by this invention adopts following technical scheme to realize.
A kind of gentamycin sulfate compositions, the prescription of said composition is made up of principal agent and accessory drugs, it is characterized in that: principal agent is a gentamycin sulfate, accessory drugs be chosen as skeleton agent (mannitol), forming agent (gelatin), correctives (sucralose).
A kind of gentamycin sulfate compositions is characterized in that, said composition comprises following component and component quantity ratio:
The preferred ingredient quantity ratio of said each component of gentamycin sulfate compositions is:
Another object of the present invention provides a kind of gentamycin sulfate composition freeze-drying oral cavity disintegration tablet that contains above-mentioned gentamycin sulfate compositions.This freeze-dry orally disintegrating tablet component is simple, need not water when taking, and need not to chew, and disintegration time was no more than for 2 seconds in human oral cavity; Rapid-action, intestinal is residual few, and liver first-pass effect is little, absorbs fully; Side effect is low, and mouthfeel is good, is particularly suitable for the infant patient and takes.
A kind of gentamycin sulfate composition freeze-drying oral cavity disintegration tablet that contains above-mentioned gentamycin sulfate compositions is characterized in that, is prepared from following component and component quantity ratio:
The preferred ingredient quantity ratio of each component of preparation gentamycin sulfate composition freeze-drying oral cavity disintegration tablet is:
A further object of the present invention provides a kind of method for preparing of gentamycin sulfate composition freeze-drying oral cavity disintegration tablet, and this method is applicable to that water is prone to dissolve and insoluble drug, and preparation condition is gentle, is easy to control, is fit to industrialized great production.
For realizing a further object of the present invention, a kind of method for preparing of gentamycin sulfate composition freeze-drying oral cavity disintegration tablet is provided, adopt following technical scheme:
A) in the water for injection of recipe quantity, under stirring, slowly add the gentamycin sulfate of recipe quantity, preparation solution a;
B) mannitol, the sucralose with recipe quantity adds solution a, is stirred to dissolving fully, preparation solution b;
C) gelatin with recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30%, is heated to dissolving fully, preparation solution c;
D) merge above-mentioned a, b, three kinds of solution of c and stir, regulate pH value to 4.0-6.0 with sodium bicarbonate;
E) according to gentamycin sulfate composition freeze-drying oral cavity disintegration tablet specification; After confirming loading amount, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box; Medicinal liquid is carried out freezing (cryogenic temperature is-20 ℃--50 ℃); Evacuation dry (baking temperature is at+5 ℃-+20 ℃, vacuum be-more than the 0.09MPa) is controlled moisture and is no more than 1.0%;
F) treat gentamycin sulfate composition freeze-drying oral cavity disintegration tablet drying after, in freeze drying box, seal;
G) cut drug-containing dish after the medicament that freezes is taken out freeze drying box, and carry out finished product packing.
Said gentamycin sulfate composition freeze-drying oral cavity disintegration tablet specification is 40mg/ sheet or 80mg/ sheet.
We have formulated relevant detection method for the disintegration rate of gentamycin sulfate composition freeze-drying oral cavity disintegration tablet:
Disintegration
According to inspection technique disintegration (two appendix ⅹ of Chinese Pharmacopoeia version in 2010 A); The stainless steel shaft of hanging basket through the upper end hung on the metal rack; Immerse in the 1000ml beaker; And screen cloth fills temperature and is 37 ℃ ± 1 ℃ water apart from beaker bottom 25mm in the beaker when regulating the hanging basket position it being descended, when regulating height of water level hanging basket being risen screen cloth in the underwater 15mm place.
Except as otherwise herein provided, get 4 groups of test samples (every group of dosage is 80mg), put respectively in the glass tubing of above-mentioned hanging basket, add baffle plate, start disintegration tester and check, each sheet all should all disintegrates in 1.1 seconds.Result such as following table:
Dosage equates, the disintegration time and the medicine of different gentamycin sulfate tablets agent reach peak concentration
As stated above to gentamycin sulfate composition freeze-drying oral cavity disintegration tablet of the present invention and gentamycin sulfate ordinary tablet comparative determination; The present invention is up to specification; The gentamycin sulfate ordinary tablet disintegration can not be qualified, and the disintegration rate of gentamycin sulfate composition freeze-drying oral cavity disintegration tablet of the present invention is far longer than the gentamycin sulfate ordinary tablet.This dosage form has following advantage:
First disintegrate is rapid, and drug effect is fast.Gentamycin sulfate composition freeze-drying oral cavity disintegration tablet of the present invention is disintegrate rapidly in 2 seconds in mouth, is beneficial to the rapid stripping of medicine, shortens dissolution time, accelerates to absorb, and liver first-pass effect is little, makes its performance curative effect fast.
Second drug absorption is abundant.Gentamycin sulfate composition freeze-drying oral cavity disintegration tablet of the present invention is disintegrate fully in the oral cavity, makes the absorption of medicine more abundant, helps improving bioavailability of medicament like this.
The 3rd taking convenience, mouthfeel is good.Gentamycin sulfate composition freeze-drying oral cavity disintegration tablet of the present invention needn't be used water delivery service, and saliva can make its complete disintegrate, and no foreign body sensation in mouthful is owing to wherein add the compliance that the sweet child of helping of suitable correctives cool taste flavor takes medicine.Compare with liquid preparation and dosage advantage accurately arranged.
The present invention adopts new freeze-drying preparation technology to produce, and is applicable to that water is prone to dissolve and insoluble drug, and preparation condition is gentle, is easy to control, is fit to industrialized great production.
The selected adjuvant of gentamycin sulfate composition freeze-drying oral cavity disintegration tablet of the present invention all is the adjuvants that are suitable for this tablet of preparation.
Since gentamycin sulfate composition freeze-drying oral cavity disintegration tablet of the present invention mainly in order to satisfy child's medication demand, and the gentamycin sulfate taste is pungent, for improving the compliance of children, in prescription, has added the correctives sucralose.In traditional production application, aspartame flavour mouthfeel is pretty good, but is prone to decompose instability; Cyclamate, glucide safety receive dispute to a certain degree, and are prone to produce the back bitterness.And the sucralose sweet feel is very near sucrose, and is very stable, safe to heat, acid, alkali.Simultaneously, sucralose is not utilized by the dental caries pathogenic bacteria, can reduce pathogenic bacteria in the oral cavity, and the acid amount of generation and streptococcus cell effectively play the dental caries effect in the adhesion of dental surface, and useful especially teenager teeth is healthy; The sucralose good stability can long term storage, and in freezing dry process, can not be damaged, and is fit to industrial applications.
The specific embodiment:
For technological means, creation characteristic that the present invention is realized, reach purpose and effect and be easy to understand and understand, below in conjunction with specific embodiment, further set forth the present invention.
Embodiment 1
With the 80mg/ sheet is that example prepares gentamycin sulfate composition freeze-drying oral cavity disintegration tablet
Prescription: 1000 amounts
Preparation technology:
In the water for injection of recipe quantity, under stirring, slowly add the gentamycin sulfate of recipe quantity, preparation solution a; Mannitol, the sucralose of recipe quantity are added solution a, be stirred to dissolving fully, preparation solution b; The gelatin of recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30%, is heated to dissolving fully, preparation solution c; Merge above-mentioned a, b, three kinds of solution of c and stir, regulate pH value to 4.0-6.0 with sodium bicarbonate; According to gentamycin sulfate composition freeze-drying oral cavity disintegration tablet specification; After confirming loading amount, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box; Medicinal liquid is carried out freezing (cryogenic temperature is-20 ℃--50 ℃); Evacuation dry (baking temperature is at+5 ℃-+20 ℃, vacuum be-more than the 0.09MPa) is controlled moisture and is no more than 1.0%; After treating gentamycin sulfate composition freeze-drying oral cavity disintegration tablet drying, in freeze drying box, seal; Cut drug-containing dish after the medicament that freezes taken out freeze drying box, and carry out finished product packing.
Embodiment 2
With the 80mg/ sheet is that example prepares gentamycin sulfate composition freeze-drying oral cavity disintegration tablet
Prescription: 1000 amounts
Preparation technology:
In the water for injection of recipe quantity, under stirring, slowly add the gentamycin sulfate of recipe quantity, preparation solution a; Mannitol, the sucralose of recipe quantity are added solution a, be stirred to dissolving fully, preparation solution b; The gelatin of recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30%, is heated to dissolving fully, preparation solution c; Merge above-mentioned a, b, three kinds of solution of c and stir, regulate pH value to 4.0-6.0 with sodium bicarbonate; According to gentamycin sulfate composition freeze-drying oral cavity disintegration tablet specification; After confirming loading amount, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box; Medicinal liquid is carried out freezing (cryogenic temperature is-20 ℃--50 ℃); Evacuation dry (baking temperature is at+5 ℃-+20 ℃, vacuum be-more than the 0.09MPa) is controlled moisture and is no more than 1.0%; After treating gentamycin sulfate composition freeze-drying oral cavity disintegration tablet drying, in freeze drying box, seal; Cut drug-containing dish after the medicament that freezes taken out freeze drying box, and carry out finished product packing.
Embodiment 3
With the 80mg/ sheet is that example prepares gentamycin sulfate composition freeze-drying oral cavity disintegration tablet
Prescription: 1000 amounts
Preparation technology:
In the water for injection of recipe quantity, under stirring, slowly add the gentamycin sulfate of recipe quantity, preparation solution a; Mannitol, the sucralose of recipe quantity are added solution a, be stirred to dissolving fully, preparation solution b; The gelatin of recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30%, is heated to dissolving fully, preparation solution c; Merge above-mentioned a, b, three kinds of solution of c and stir, regulate pH value to 4.0-6.0 with sodium bicarbonate; According to gentamycin sulfate composition freeze-drying oral cavity disintegration tablet specification; After confirming loading amount, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box; Medicinal liquid is carried out freezing (cryogenic temperature is-20 ℃--50 ℃); Evacuation dry (baking temperature is at+5 ℃-+20 ℃, vacuum be-more than the 0.09MPa) is controlled moisture and is no more than 1.0%; After treating gentamycin sulfate composition freeze-drying oral cavity disintegration tablet drying, in freeze drying box, seal; Cut drug-containing dish after the medicament that freezes taken out freeze drying box, and carry out finished product packing.
The present invention adopts novel freeze-drying to prepare oral cavity disintegration tablet, is applicable to that water is prone to dissolve and insoluble drug, and technology is simple, is easy to control, is fit to suitability for industrialized production.Gentamycin sulfate freeze-dry orally disintegrating tablet component of the present invention is simple, need not water when taking, and need not to chew; Disintegration time was no more than for 2 seconds in human oral cavity, absorbed soon, and bioavailability is high; Intestinal is residual few, and side effect is low, and liver first-pass effect is little; Mouthfeel is good, is particularly suitable for the infant patient and takes.
More than show and described ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; The present invention is not restricted to the described embodiments; That describes in the foregoing description and the description is merely preference of the present invention, is not used for limiting the present invention, under the prerequisite that does not break away from spirit and scope of the invention; The present invention also has various changes and modifications, and these variations and improvement all fall in the scope of the invention that requires protection.The present invention requires protection domain to be defined by appending claims and equivalent thereof.
Claims (6)
1. a gentamycin sulfate compositions is characterized in that, said composition comprises following component and component quantity ratio:
2. gentamycin sulfate compositions according to claim 1 is characterized in that, the preferred ingredient quantity ratio of said each component of gentamycin sulfate compositions is:
3. a gentamycin sulfate composition freeze-drying oral cavity disintegration tablet that contains the said compositions of claim 1 is characterized in that, is prepared from following component and component quantity ratio:
4. gentamycin sulfate composition freeze-drying oral cavity disintegration tablet according to claim 3 is characterized in that, the preferred ingredient quantity ratio of each component of preparation gentamycin sulfate composition freeze-drying oral cavity disintegration tablet is:
5. the method for preparing of the said gentamycin sulfate composition freeze-drying of claim 3 oral cavity disintegration tablet is characterized in that the concrete steps of this method for preparing are:
A) in the water for injection of recipe quantity, under stirring, slowly add the gentamycin sulfate of recipe quantity, preparation solution a;
B) mannitol, the sucralose with recipe quantity adds solution a, is stirred to dissolving fully, preparation solution b;
C) gelatin with recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30%, is heated to dissolving fully, preparation solution c;
D) merge above-mentioned a, b, three kinds of solution of c and stir, regulate pH value to 4.0-6.0 with sodium bicarbonate;
E) according to gentamycin sulfate composition freeze-drying oral cavity disintegration tablet specification, confirm loading amount after, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and puts into freeze drying box, medicinal liquid is carried out freezing, the dry control moisture of evacuation is no more than 1.0%;
F) treat gentamycin sulfate composition freeze-drying oral cavity disintegration tablet drying after, in freeze drying box, seal;
G) cut drug-containing dish after the medicament that freezes is taken out freeze drying box, and carry out finished product packing.
6. the method for preparing of gentamycin sulfate composition freeze-drying oral cavity disintegration tablet according to claim 5 is characterized in that: said gentamycin sulfate composition freeze-drying oral cavity disintegration tablet specification is 40mg/ sheet or 80mg/ sheet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012103007075A CN102784117A (en) | 2012-08-23 | 2012-08-23 | Gentamicin sulfate composition freeze-dried orally disintegrating tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012103007075A CN102784117A (en) | 2012-08-23 | 2012-08-23 | Gentamicin sulfate composition freeze-dried orally disintegrating tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102784117A true CN102784117A (en) | 2012-11-21 |
Family
ID=47149839
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012103007075A Pending CN102784117A (en) | 2012-08-23 | 2012-08-23 | Gentamicin sulfate composition freeze-dried orally disintegrating tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102784117A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1139878A (en) * | 1994-01-31 | 1997-01-08 | 山之内制药株式会社 | Intraorally soluble compressed molding and process for producing the same |
| CN101925349A (en) * | 2007-12-21 | 2010-12-22 | 欧兰德股份有限公司 | Orally disintegrating tablet compositions of temazepam |
| WO2011053251A1 (en) * | 2009-10-30 | 2011-05-05 | Ix Biopharma Pte Ltd | Fast dissolving solid dosage form |
| US20120076858A1 (en) * | 2009-06-04 | 2012-03-29 | Basf Se | Orally Disintegrating Dosage Forms Containing Taste-Masked Active Ingredients |
| CN102579378A (en) * | 2012-02-07 | 2012-07-18 | 海南卫康制药(潜山)有限公司 | Child cefdinir composition freeze-dried oral disintegrating tablet and preparation method thereof |
-
2012
- 2012-08-23 CN CN2012103007075A patent/CN102784117A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1139878A (en) * | 1994-01-31 | 1997-01-08 | 山之内制药株式会社 | Intraorally soluble compressed molding and process for producing the same |
| CN101925349A (en) * | 2007-12-21 | 2010-12-22 | 欧兰德股份有限公司 | Orally disintegrating tablet compositions of temazepam |
| US20120076858A1 (en) * | 2009-06-04 | 2012-03-29 | Basf Se | Orally Disintegrating Dosage Forms Containing Taste-Masked Active Ingredients |
| WO2011053251A1 (en) * | 2009-10-30 | 2011-05-05 | Ix Biopharma Pte Ltd | Fast dissolving solid dosage form |
| CN102579378A (en) * | 2012-02-07 | 2012-07-18 | 海南卫康制药(潜山)有限公司 | Child cefdinir composition freeze-dried oral disintegrating tablet and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102579378B (en) | Child cefdinir composition freeze-dried oral disintegrating tablet and preparation method thereof | |
| AU2015289150B2 (en) | Orodispersible film | |
| CN102631336B (en) | Freeze-drying orally disintegrating tablet with vitamin K1 composition for infants and preparation method for freeze-drying orally disintegrating tablet | |
| CN103784426A (en) | Aripiprazole oral membrane and preparation method thereof | |
| RU2755087C1 (en) | Composite compound of paracetamol for oral use | |
| CN102600119B (en) | Pediatric acetaminophen composition | |
| CN102525978B (en) | Children amoxicillin-potassium clavulanate composition | |
| CN102772383A (en) | Azithromycin composition freeze-dried orally disintegrating tablet and preparation method thereof | |
| CN102784119A (en) | Roxithromycin composition freeze-dried orally disintegrating tablets and preparation method thereof | |
| US20200261362A1 (en) | Solution Preparation for Aerosol Inhalation of Carbocisteine, and Preparation Method Therefor | |
| CN102525979B (en) | Infant ibuprofen composition | |
| JP2003192573A (en) | Oral gel preparation | |
| CN102784121A (en) | Levofloxacin composition freeze-dried orally disintegrating tablets and preparation method thereof | |
| CN102614212B (en) | Freeze-dried orally disintegrating tablets of pediatric ribavirin composition, and preparation method thereof | |
| CN102784118A (en) | Fosfomycin calcium composition freeze-dried orally disintegrating tablets and preparation method thereof | |
| CN102525980B (en) | Children cetirizine hydrochloride composition | |
| CN102648899B (en) | Child cefalexin composition | |
| CN102784117A (en) | Gentamicin sulfate composition freeze-dried orally disintegrating tablet and preparation method thereof | |
| CN102940610A (en) | Vitamin B6 composition freeze-drying orally disintegrating tablets and preparation method thereof | |
| CN104780907A (en) | Medicinal lozenge based on ibuprofen sodium dihydrate | |
| CN102784122A (en) | Isoniazid composition freeze-dried orally disintegrating tablet and preparation method thereof | |
| CN102600153B (en) | Pediatric compound anisodamine hydrobromide and chlorpheniramine maleate freeze-dried orally disintegrating tablets and manufacturing method thereof | |
| CN102784124A (en) | Cefuroxime axetil composition freeze-dried orally disintegrating tablets and preparation method thereof | |
| CN103239478A (en) | Calcium carbonate milk composition freeze-dried orally disintegrating tablets, and preparation method thereof | |
| CN102784125A (en) | Cefetamet pivoxil composition freeze-dried orally disintegrating tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20121121 |