CN103070829A - Medicine composition including pramipexole and active ingredients of medicinal salt and preparation method thereof - Google Patents
Medicine composition including pramipexole and active ingredients of medicinal salt and preparation method thereof Download PDFInfo
- Publication number
- CN103070829A CN103070829A CN2012105897809A CN201210589780A CN103070829A CN 103070829 A CN103070829 A CN 103070829A CN 2012105897809 A CN2012105897809 A CN 2012105897809A CN 201210589780 A CN201210589780 A CN 201210589780A CN 103070829 A CN103070829 A CN 103070829A
- Authority
- CN
- China
- Prior art keywords
- pramipexole
- preparation
- pharmaceutical composition
- percentage
- weight
- 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 belongs to the technical field of medicines and particularly relates to a medicine composition including pramipexole and a preparation method thereof. The medicine composition comprises pramipexole and active ingredients of medicinal salt, as well as pharmaceutically acceptable pharmaceutic adjuvant. According to the invention, wet granulation is adopted, and pramipexole is added into and mixed with an adhesive, so that the stability is good, the content is uniform, disintegration is fast, the operation is simple and the medicine composition can take a good curative effect on treatment of Parkinson's disease.
Description
Technical field
The invention belongs to medical technical field, relate to pharmaceutical composition of a kind of active component that contains pramipexole and officinal salt thereof and preparation method thereof.
Background technology
Pramipexole is known dopamine D
2Receptor stimulating agent.For example the structure of pergolide is different from the Ergota drug derivative for they.It is pharmacology's uniqueness, because it is full agonist, to the dopamine D of dopamine receptor
2Family has receptor-selective.
The chemical name of pramipexole is: (S)-2-amino-4,5,6,7-tetrahydrochysene-6-(the third amino) benzothiazole, molecular formula is C
10H
17N
3S, relative molecular weight are 211.33.Chemical formula is as follows:
Normally used pramipexole salt form is the monohydrate that pramipexole contains two hydrochlorate molecules, and chemical formula is C
10H
17N
3S2HClH
2O, molecular weight are 302.27.The pramipexole dihydrochloride monohydrate is that white is to canescence, tasteless, crystal powder.Fusing point is 296 ℃-301 ℃, decomposes simultaneously.The dissolubility of this material be in water greater than 20%, about 8% in methanol, about 0.5% in ethanol, be dissolved in hardly chloroform.
The pramipexole dihydrochloride monohydrate is easy melting chemical compound.Water solubility is greater than 20mg/ml, and the dissolubility in the buffer medium of PH2 to PH7.4 is usually above 10mg/ml.The pramipexole dihydrochloride monohydrate is the non-hygroscopic medicine, has high crystalline matter.Under grinding, crystalline modifications (monohydrate) can not change.Pramipexole solid-state highly stable, however its solution is very sensitive to light.
Pramipexole discharges (IR) tablet immediately by the exploitation of German Boehringer Ingelheim company, on May 10th, 1997, at first in U.S.'s approval listing, trade name Mirapex is sold by BoehringerIngelheim company and Pharmacia company jointly in the U.S..It is FDA ratifies to be used for parkinson in the past first in 6 years medicine.In subsequently several years, obtain respectively the market approval European Union (EU), Switzerland, Canada and South America and in East Bloc, the Near East and Asia.
Parkinson disease belong to central nervous system degenerative disease, the patient many at 60 years old with sequela.Main manifestations is that patient motion is slow, the trembling of the other parts of trick or health, and health has lost flexibility and harmony.This disease there is no the method for thorough healing at present, needs Drug therapy long-term, that continue, suppresses disease progression.Therefore, for such patient, need a kind ofly to be easy to take, side effect is little, stable curative effect, toleration and the good medicine of compliance.
Pramipexole is used for the treatment of old people's parkinson disease (Parkinson ' s disease); can use separately treatment in early days; can share the treatment parkinson late period with dopamine; the external while is used for the treatment of RLS disease (restless leg syndrome) for pramipexole and studies; think effectively; and pramipexole has protective effect to the nerve of dopamine; the treatment of neuroprotective and RLS disease is its unique advantage; can greatly delay the development of the state of an illness, guarantee patient's health.After oral, pramipexole absorbs rapidly fully, reaches peak concentration in 2 hours, and absolute bioavailability is higher than 90%, and maximal plasma concentration occurs between 1-3 hour after taking medicine.Take the degree that can not reduce the pramipexole absorption with food, but can reduce its absorption rate.Pramipexole demonstrates the linear kinetics characteristics, and blood plasma level difference is very little between the patient.The main removing approach of pramipexole from renal excretion with original shape.Young and old people's pramipexole is removed half-life (t
1/2) do not wait from 8-12 hour.
Patent documentation CN101401796A discloses pramipexole orally disintegrating tablets and preparation method thereof; Patent documentation CN101766605A discloses a kind of drug regimen that can disperse that comprises pramipexole in mouth; Importance of the present invention and necessity have been confirmed.
Technological operation of the present invention is simple, and good stability is compared with other listing dosage forms, and production cost is low, is fit to industrialized great production.
Summary of the invention
The invention provides pharmaceutical composition of a kind of active component that contains pramipexole and officinal salt thereof and preparation method thereof, take the active component of pramipexole and officinal salt thereof as active component, add that pharmaceutically acceptable adjuvant is prepared into oral solid formulation, exists with tablet, granule and capsule.Preparation technology is simple to operate, and production cost is low, is fit to suitability for industrialized production.
The active component of described pramipexole and officinal salt thereof percentage by weight in pharmaceutical composition is 0.1%-10%, and pharmaceutic adjuvant percentage by weight in pharmaceutical composition is 90%-99.9%.
In the described pharmaceutical composition, contain an amount of pharmaceutically acceptable adjuvant, comprising: filler, disintegrating agent, binding agent, lubricant; Described filler is selected from a kind of in lactose, mannitol, pregelatinized Starch, the sorbitol or several mixture wherein; Described disintegrating agent is selected from a kind of in polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, the corn starch or several mixture wherein; Described binding agent is selected from a kind of in polyvinylpolypyrrolidone, starch slurry, the hydroxypropyl cellulose or several mixture wherein; Described lubricant is selected from a kind of in Pulvis Talci, differential silica gel, the magnesium stearate or several mixture wherein.
Described pharmaceutic adjuvant shared percentage by weight in pharmaceutical composition is respectively: filler is 35%-70%, and disintegrating agent is 5%-50%, and binding agent is 1%-5%, and lubricant is 0.5%-5%.
Described pharmaceutical composition form of medication can be tablet, granule or capsule.
Described pharmaceutical composition preparation method comprises following steps:
1) active component of pramipexole and officinal salt thereof is crossed the 80-100 mesh sieve, for subsequent use;
2) filler, disintegrating agent, binding agent, lubricant are crossed respectively the 60-80 mesh sieve, for subsequent use;
3) active component with pramipexole and officinal salt thereof joins in the aqueous solution of binding agent, mixes 30-60min, and is for subsequent use; After filler, disintegrating agent fully mixed, add binding agent soft material processed of the active component that contains in right amount pramipexole and officinal salt thereof, cross 16 mesh sieves and granulate, after the drying, mistake 24 mesh sieve granulate obtain granule I;
4) add lubricant in granule I, mix homogeneously obtains granule II;
According to aforesaid preparation method, wherein, described preparation method also comprises carries out tabletting with resulting pharmaceutical composition.
According to aforesaid preparation method, wherein, step 3) drying described in is baking 2-4 hour under 40-60 ℃ of condition.
According to aforesaid preparation method, wherein, described tabletting is to control the hardness of slice, thin piece at 35-60N.
One aspect of the present invention provides a kind of pharmaceutical composition that contains the active component of pramipexole and officinal salt thereof, and this pharmaceutical composition has good stability, and disintegrate is rapid, and drug-eluting is fast, absorbs rapidly the advantage that bioavailability is high; Production technology is simple on the other hand, and production cost is low, and its medicine makes patient's taking convenience, good effect.
The specific embodiment
The present invention is described in detail in conjunction with the embodiments, but be not limited to following embodiment.
The existence form of embodiment 1 this embodiment is tablet
Preparation technology: take by weighing the pramipexole dihydrochloride monohydrate by recipe quantity, cross 100 mesh sieves, for subsequent use.Take by weighing mannitol, the corn starch of recipe quantity, cross 80 mesh sieves, behind the mix homogeneously, add 5% polyvinylpolypyrrolidone aqueous solution (wherein contain the pramipexole dihydrochloride monohydrate of recipe quantity, and mix 30-60min) soft material processed, 16 mesh sieves are granulated.Drying is measured moisture; 24 mesh sieve granulate take by weighing differential silica gel, the magnesium stearate of recipe quantity, with the granule mix homogeneously.Ф 6mm scrobicula stamping and get final product
The existence form of embodiment 2 these embodiment is tablet
Preparation technology: take by weighing the pramipexole dihydrochloride monohydrate by recipe quantity, cross 100 mesh sieves, for subsequent use.Take by weighing mannitol, the corn starch of recipe quantity, cross 80 mesh sieves, behind the mix homogeneously, add 5% polyvinylpolypyrrolidone aqueous solution (wherein contain the pramipexole dihydrochloride monohydrate of recipe quantity, and mix 30-60min) soft material processed, 16 mesh sieves are granulated.Drying is measured moisture; 24 mesh sieve granulate take by weighing differential silica gel, the magnesium stearate of recipe quantity, with the granule mix homogeneously.Ф 6mm scrobicula stamping and get final product.
The existence form of embodiment 3 these embodiment is tablet
Preparation technology: take by weighing the pramipexole dihydrochloride monohydrate by recipe quantity, cross 100 mesh sieves, for subsequent use.Take by weighing mannitol, the corn starch of recipe quantity, cross 80 mesh sieves, behind the mix homogeneously, add 5% polyvinylpolypyrrolidone aqueous solution (wherein contain the pramipexole dihydrochloride monohydrate of recipe quantity, and mix 30-60min) soft material processed, 16 mesh sieves are granulated.Drying is measured moisture; 24 mesh sieve granulate take by weighing differential silica gel, the magnesium stearate of recipe quantity, with the granule mix homogeneously.Ф 6mm scrobicula stamping and get final product.
The existence form of embodiment 4 these embodiment is tablet
Preparation technology: take by weighing the pramipexole dihydrochloride monohydrate by recipe quantity, cross 100 mesh sieves, for subsequent use.Take by weighing mannitol, the corn starch of recipe quantity, cross 80 mesh sieves, behind the mix homogeneously, add 5% polyvinylpolypyrrolidone aqueous solution (wherein contain the pramipexole dihydrochloride monohydrate of recipe quantity, and mix 30-60min) soft material processed, 16 mesh sieves are granulated.Drying is measured moisture; 24 mesh sieve granulate take by weighing differential silica gel, the magnesium stearate of recipe quantity, with the granule mix homogeneously.Ф 6mm scrobicula stamping and get final product.
The existence form of embodiment 5 these embodiment is tablet
Preparation technology: take by weighing the pramipexole dihydrochloride monohydrate by recipe quantity, cross 100 mesh sieves, for subsequent use.Take by weighing mannitol, the corn starch of recipe quantity, cross 80 mesh sieves, behind the mix homogeneously, add 5% polyvinylpolypyrrolidone aqueous solution (wherein contain the pramipexole dihydrochloride monohydrate of recipe quantity, and mix 30-60min) soft material processed, 16 mesh sieves are granulated.Drying is measured moisture; 24 mesh sieve granulate take by weighing differential silica gel, the magnesium stearate of recipe quantity, with the granule mix homogeneously.Ф 6mm scrobicula stamping and get final product.
The existence form of embodiment 6 these embodiment is tablet
Preparation technology: take by weighing the pramipexole dihydrochloride monohydrate by recipe quantity, cross 100 mesh sieves, for subsequent use.Take by weighing mannitol, the corn starch of recipe quantity, cross 80 mesh sieves, behind the mix homogeneously, add 5% polyvinylpolypyrrolidone aqueous solution (wherein contain the pramipexole dihydrochloride monohydrate of recipe quantity, and mix 30-60min) soft material processed, 16 mesh sieves are granulated.Drying is measured moisture; 24 mesh sieve granulate take by weighing differential silica gel, the magnesium stearate of recipe quantity, with the granule mix homogeneously.Ф 6mm scrobicula stamping and get final product.
The existence form of embodiment 7 these embodiment is capsule
Preparation technology: take by weighing the pramipexole dihydrochloride monohydrate by recipe quantity, cross 100 mesh sieves, for subsequent use.Take by weighing mannitol, the corn starch of recipe quantity, cross 80 mesh sieves, behind the mix homogeneously, add 5% polyvinylpolypyrrolidone aqueous solution (wherein contain the pramipexole dihydrochloride monohydrate of recipe quantity, and mix 30-60min) soft material processed, 16 mesh sieves are granulated.Drying is measured moisture; 24 mesh sieve granulate take by weighing differential silica gel, the magnesium stearate of recipe quantity, with the granule mix homogeneously.Namely get granule.The 4# capsule shells is filled.
The existence form of embodiment 8 these embodiment is granule
Preparation technology: take by weighing the pramipexole dihydrochloride monohydrate by recipe quantity, cross 100 mesh sieves, for subsequent use.Take by weighing mannitol, the corn starch of recipe quantity, cross 80 mesh sieves, behind the mix homogeneously, add 5% polyvinylpolypyrrolidone aqueous solution (wherein contain the pramipexole dihydrochloride monohydrate of recipe quantity, and mix 30-60min) soft material processed, 16 mesh sieves are granulated.Drying is measured moisture; 24 mesh sieve granulate take by weighing differential silica gel, the magnesium stearate of recipe quantity, with the granule mix homogeneously.Packing namely gets granule.
The sample of 9 pairs of embodiment 1-8 preparations of embodiment carries out dissolution determination.
Sample 1-8 according to embodiment 1-8 preparation carries out dissolution determination respectively, wherein dissolution adopts " the second method in two appendix XC of Chinese pharmacopoeia version in 2010 dissolution method, take 500ml, pH6.8 phosphate buffer as medium, rotating speed is 50rpm, respectively at 5,15,30,45 minutes sampling test sample dissolutions, the results are shown in Table 1:
The dissolution % (n=6) of table 1 embodiment 1-8 in the pH6.8PBS medium
The sample of 10 couples of embodiment of embodiment, 3 preparations carries out accelerated stability test, and the result is as follows:
Know that therefrom not only dissolution is high for the sample that this pharmaceutical composition that contains the active component of pramipexole and officinal salt thereof prepares, good stability, and preparation technology is simple, and cost is low, is conducive to suitability for industrialized production.
Claims (6)
1. the preparation method of a pramipexole pharmaceutical composition, the active component and the pharmaceutically acceptable pharmaceutic adjuvant that contain pramipexole and officinal salt thereof, the percentage by weight of pramipexole is 0.1%-10%, and the percentage by weight of adjuvant is 90%-99.9%; Adjuvant is selected from filler, disintegrating agent, binding agent, lubricant; Described filler is selected from a kind of in lactose, mannitol, pregelatinized Starch, the sorbitol or several mixture wherein, and the percentage by weight of filler is 35%-70%; Described disintegrating agent is selected from a kind of in polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, the corn starch or several mixture wherein, and the percentage by weight of disintegrating agent is 5%-50%; Described binding agent is selected from a kind of in polyvinylpolypyrrolidone, starch slurry, the hydroxypropyl cellulose or several mixture wherein, and the percentage by weight that accounts for pharmaceutical composition is 1%-5%; Described lubricant is selected from a kind of in Pulvis Talci, differential silica gel, the magnesium stearate or several mixture wherein, and the percentage by weight that accounts for pharmaceutical composition is 0.5%-5%;
2. pharmaceutical composition according to claim 1, the form of medication that it is characterized in that said composition is tablet, granule or capsule, is preferably tablet.
3. the preparation method of pharmaceutical composition according to claim 1 is characterized in that, described preparation comprises following steps:
1) active component of pramipexole and officinal salt thereof is crossed the 80-100 mesh sieve, for subsequent use;
2) filler, disintegrating agent, binding agent, lubricant are crossed respectively the 60-80 mesh sieve, for subsequent use;
3) active component with pramipexole and officinal salt thereof joins in the aqueous solution of binding agent, mixes 30-60min, and is for subsequent use; After filler, disintegrating agent fully mixed, add binding agent soft material processed of the active component that contains in right amount pramipexole and officinal salt thereof, cross 16 mesh sieves and granulate, after the drying, mistake 24 mesh sieve granulate obtain granule I;
4) add lubricant in granule I, mix homogeneously obtains granule II;
4. preparation method according to claim 3 is characterized in that, described preparation method also comprises carries out tabletting with resulting pharmaceutical composition.
5. preparation method according to claim 3 is characterized in that step 3) described in drying be under 40-60 ℃ of condition the baking 2-4 hour.
6. preparation method according to claim 4 is characterized in that, described tabletting is to control the hardness of slice, thin piece at 35-60N.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012105897809A CN103070829A (en) | 2012-12-21 | 2012-12-21 | Medicine composition including pramipexole and active ingredients of medicinal salt and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012105897809A CN103070829A (en) | 2012-12-21 | 2012-12-21 | Medicine composition including pramipexole and active ingredients of medicinal salt and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103070829A true CN103070829A (en) | 2013-05-01 |
Family
ID=48147678
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012105897809A Pending CN103070829A (en) | 2012-12-21 | 2012-12-21 | Medicine composition including pramipexole and active ingredients of medicinal salt and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103070829A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103271890A (en) * | 2013-06-26 | 2013-09-04 | 北京华睿鼎信科技有限公司 | Hydrochloric acid pramipexole capsule and preparation method thereof |
| CN104666259A (en) * | 2015-01-30 | 2015-06-03 | 华润赛科药业有限责任公司 | Pramipexole hydrochloride tablet and preparation method thereof |
| CN105769841A (en) * | 2014-08-12 | 2016-07-20 | 烟台市华文欣欣医药科技有限公司 | Application of syringic acid/4-hydroxy-3,5-dimethoxybenzoic acid in preparing drug for pregnancy termination |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101505734A (en) * | 2006-08-24 | 2009-08-12 | 贝林格尔英格海姆法玛两合公司 | Process for preparing pramipexole dihydrochloride tablets with high storage stability |
| EP2308464A1 (en) * | 2009-10-06 | 2011-04-13 | Sanovel Ilac Sanayi ve Ticaret A.S. | Orally disintegrating compositions of pramipexole |
| CN102772403A (en) * | 2011-05-10 | 2012-11-14 | 浙江京新药业股份有限公司 | Preparation method for pramipexole preparation |
-
2012
- 2012-12-21 CN CN2012105897809A patent/CN103070829A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101505734A (en) * | 2006-08-24 | 2009-08-12 | 贝林格尔英格海姆法玛两合公司 | Process for preparing pramipexole dihydrochloride tablets with high storage stability |
| EP2308464A1 (en) * | 2009-10-06 | 2011-04-13 | Sanovel Ilac Sanayi ve Ticaret A.S. | Orally disintegrating compositions of pramipexole |
| CN102772403A (en) * | 2011-05-10 | 2012-11-14 | 浙江京新药业股份有限公司 | Preparation method for pramipexole preparation |
Non-Patent Citations (1)
| Title |
|---|
| 张志荣: "《药剂学》", 31 December 2007 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103271890A (en) * | 2013-06-26 | 2013-09-04 | 北京华睿鼎信科技有限公司 | Hydrochloric acid pramipexole capsule and preparation method thereof |
| CN103271890B (en) * | 2013-06-26 | 2015-02-04 | 北京华睿鼎信科技有限公司 | Hydrochloric acid pramipexole capsule and preparation method thereof |
| CN105769841A (en) * | 2014-08-12 | 2016-07-20 | 烟台市华文欣欣医药科技有限公司 | Application of syringic acid/4-hydroxy-3,5-dimethoxybenzoic acid in preparing drug for pregnancy termination |
| CN104666259A (en) * | 2015-01-30 | 2015-06-03 | 华润赛科药业有限责任公司 | Pramipexole hydrochloride tablet and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102631347B (en) | Gefinitib medicinal composite and method for preparing same | |
| CN107080742B (en) | Solid dosage form pharmaceutical composition for oral administration | |
| KR101977785B1 (en) | Composite formulation for oral administration comprising ezetimibe and rosuvastatin and a process for the preparation thereof | |
| WO2004054574A1 (en) | Solid drug for oral use | |
| CN103845326A (en) | Compound composition of vildagliptin and melbine and preparation method thereof | |
| CN109875972B (en) | Olmesartan medoxomil and amlodipine pharmaceutical composition | |
| KR101485421B1 (en) | Controlled-release Oral Drug Preparations and it's Manufacturing Process Containing Itopride Hydrochloride | |
| CN103070829A (en) | Medicine composition including pramipexole and active ingredients of medicinal salt and preparation method thereof | |
| GB2595140A (en) | Flupentixol/melitracen pharmaceutical composition and preparation thereof | |
| EP2295040A1 (en) | Pharmaceutical compositions of pramipexole | |
| CN105343028A (en) | Medicine composition with norfloxacin and method for preparing medicine composition | |
| CN103893138A (en) | Tablet containing linezolid crystal form III | |
| EP4011375A1 (en) | Pharmaceutical composition containing nitroxoline, nitroxoline oral solid tablet, preparation method therefor and use thereof | |
| WO2003097102A1 (en) | Pharmaceutical preparation improved in dissolving property of drug slightly soluble in water | |
| CN106421794A (en) | Drug compound for treating type II diabetes and preparation method thereof | |
| CN101422441B (en) | Nimesulide sustained-release tablet and preparation method thereof | |
| CN113908153B (en) | Buvaracetam pharmaceutical composition, preparation method and application thereof | |
| CN105769883A (en) | Compound sulfamethoxazole dispersible tablet and preparation method thereof | |
| CN102358749B (en) | Roxithromycin ambroxol tablet composite and preparing method thereof | |
| KR20150075959A (en) | Capsule containing mini-tablets comprising mosapride citrate for sustained-releasing formulation improving gastrointestinal disease and preparing the method thereof | |
| CN115518046B (en) | Voriconazole dispersible tablet and preparation method thereof | |
| CN104000821B (en) | Oral double-layer tablet containing telmisartan and amlodipine besylate and preparation method thereof | |
| KR100788454B1 (en) | Rapid-acting fomulation containing nateglinide as an active ingredient | |
| CN101766605B (en) | Pramipexole-contained pharmaceutical composition capable of being dispersed in mouth | |
| CN109966256B (en) | Pramipexole sustained-release pharmaceutical composition, preparation method and application 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 | ||
| DD01 | Delivery of document by public notice | ||
| DD01 | Delivery of document by public notice |
Addressee: Beijing Wanquan Sunshine Medical Technology Co., Ltd. Document name: Notification that Application Deemed to be Withdrawn |
|
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20130501 |