CN102698245A - Antihypertensive drug of quinapril hydrochloride and rose oil nanoemulsion - Google Patents
Antihypertensive drug of quinapril hydrochloride and rose oil nanoemulsion Download PDFInfo
- Publication number
- CN102698245A CN102698245A CN2012101635258A CN201210163525A CN102698245A CN 102698245 A CN102698245 A CN 102698245A CN 2012101635258 A CN2012101635258 A CN 2012101635258A CN 201210163525 A CN201210163525 A CN 201210163525A CN 102698245 A CN102698245 A CN 102698245A
- Authority
- CN
- China
- Prior art keywords
- quinapril hydrochloride
- rosae rugosae
- oleum rosae
- nano
- rose oil
- 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 discloses an oil-in-water type antihypertensive drug of quinapril hydrochloride and rose oil nanoemulsion. The drug comprises the following raw materials by mass percentage: 1%-18% of quinapril hydrochloride, 15%-40% of surfactant, 0-20% of cosurfactant, 1%-20% of rose oil, and the balance of distilled water, wherein the sum of the mass percentages of the materials is 100%. The nanoemulsion has the advantages of small emulsion droplet particles, uniform distribution, small viscosity and good flowability. The nanoemulsion dosage form organically combines water-soluble drugs, quinapril hydrochloride and fat-soluble rose oil, so the dissolving and penetrating abilities of the rose oil are improved, and the stability and the pesticide effect of the quinapril hydrochloride are increased. The advantages of the quinapril hydrochloride and the rose oil are combined after the quinapril hydrochloride and the rose oil are prepared into the nanoemulsion dosage form, so the antihypertensive effect is obviously increased, the half-life period of the drug is prolonged and the administration times is also reduced.
Description
Technical field
[0001] the invention belongs to field of medicaments, relate to the novel form of a kind of antihypertensive drug quinapril hydrochloride and Oleum Rosae Rugosae, particularly a kind of quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion antihypertensive drug.
Background technology
Quinapril hydrochloride (Quinapril Hydrochloride) chemical name: (3S-(2 (R* (R*)); 3R*))-2-(2-((1-(carbethoxyl group)-3-phenylpropyl) amino)-1-oxopropyl)-1; 2,3,4-tetrahydrochysene-3-isoquinolinecarboxylic acid hydrochlorate. molecular formula: C
25H
30N
2O
5HCl.Molecular weight: 438.52.Quinapril hydrochloride is a white crystalline powder; Odorless, bitter in the mouth; Have draw moist.Very easily dissolving in methanol is prone to dissolve in 0.1mol/L hydrochloric acid and chloroform, in water, dissolves.
Quinapril hydrochloride is thin basic, long-acting, oral for not having, Angiotensin-Converting (ACE) inhibitor.Oral back is hydrolyzed at liver has active two acid type chemical compounds; Be quinaprilat, can suppress ACE, the prevention angiotensin i-converting is an Angiotensin II; Thereby the vasoconstriction effect that Angiotensin II is mediated obviously weakens, and reduces the vascular resistance of tremulous pulse; Also suppress the synthetic of aldosterone simultaneously, the minimizing water that aldosterone produced and the retention of sodium further descend blood pressure.Thereby be a kind of safe, antihypertensive drugs efficiently.
Be rich in cinnamic aldehyde in the Oleum Rosae Rugosae.Cinnamic aldehyde has cis and trans two kinds of isomers, and no matter existing commercial cinnamic aldehyde is natural or synthetic cinnamic aldehyde, all is trans body.3-phenyl-2-acrylic aldehyde (Cinnamic aldehyde), structural formula: C
6H
5CHCHCHO.Molecular weight: 132.16.CAS：104-55-2。Be colourless or weak yellow liquid.Fragrance: the fragrance of intensive Oleum Cinnamomi and Oleum Cinnamomi is arranged, gentle hot fragrance breath, the pungent that do not have, fragrance is lasting strongly.Be insoluble in water, glycerol and oil alcohol, be soluble in alcohol, the ether.Can volatilize with steam.Unstable in highly acid or strongly basic medium, be prone to cause variable color, in air, be prone to oxidation.Blood vessel dilating and hypotensive effect.Adrenal cortex property hypertension there is hypotensive effect.
Have the antihypertensive drugs of example hydrochloric acid quinapril tablet now on the market; The use of Oleum Rosae Rugosae is also arranged, though can absorb not exclusively from gastrointestinal absorption after oral; The dissolution rate of medicine is slow in addition; Bioavailability is poor, and it is slow to add the quinapril hydrochloride effect, makes the drug effect of quinapril hydrochloride and Oleum Rosae Rugosae to be fully used.
Summary of the invention
To the shortcomings and deficiencies that exist in the prior art; The object of the present invention is to provide a kind of can the water soluble drug quinapril hydrochloride and the fat-soluble Oleum Rosae Rugosae of efficient blood pressure lowering being combined, and drug distribution evenly, good stability, permeability is high, dissolubility is good, bioavailability is high quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion antihypertensive drug.
The technical scheme that realizes the foregoing invention purpose is: a kind of quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion antihypertensive drug, the particle diameter that it is characterized in that this medicine are between 50.9～95.7nm, and mean diameter is 74.1nm, and its raw material and each raw materials quality percentage ratio are:
Quinapril hydrochloride 1%～18%
Surfactant 15%～40%
Cosurfactant 0～20%
Oleum Rosae Rugosae 1%～20%
All the other compositions are distilled water, and the mass percent sum of above-mentioned raw materials is 100%.
Described surfactant be in polyoxyl 40 hydrogenated castor oil, castor oil polyoxyethylene ether 40, Tween 80 or the poloxamer 188 any one or with the mixture of span80, these surfactants are to human body low toxicity, safe, non-stimulated.
Described cosurfactant is a dehydrated alcohol, 1, the mixture of any one or a few in 2-propylene glycol, PEG400 or the glycerin.
The present invention adds bland cosurfactant such as ethanol, 1 in medicine; 2-propylene glycol, glycerin or PEG400; Except the hydrotropy effect; Cosurfactant mainly is in order to adjust HLB VALUE OF SURFACTANTS (HLB), to make oil water interfacial tension further reduce, increasing the profit property and the rigidity of limitans.Cosurfactant is incorporated in the interfacial film, promotes the very formation of membranelle of radius of curvature, enlarges the breast district area of nano-emulsion.
A kind of quinapril hydrochloride of the present invention, the administration of Oleum Rosae Rugosae nano-emulsion administered through oral; Improved the dissolubility of Oleum Rosae Rugosae greatly; Reduce medicine first pass effect in vivo; Promote Oleum Rosae Rugosae gastrointestinal absorption, and novelty water soluble drug and fat-soluble medicine are organically combined, improved the treatment ability of medicine.Oleum Rosae Rugosae is fat-soluble vegetable oil, and human body is to the transhipment of medicine and absorb extremely difficultly, and nano-emulsion substrate is that Oleum Rosae Rugosae provides good dissolving environment, can absorb through lymph when oral, the barrier when overcoming first pass effect and molecule through gastrointestinal tract.Through adding Oleum Rosae Rugosae, also improved the blood pressure lowering ability of quinapril hydrochloride on the other hand, make that blood pressure lowering is more stable, better effects if.
Quinapril hydrochloride of the present invention, Oleum Rosae Rugosae nano-emulsion compared with prior art have the following advantages:
1. the diameter of aspirin particle of quinapril hydrochloride of the present invention, Oleum Rosae Rugosae resisting hypertension nano-emulsion is between 50.9～95.7nm; Mean diameter is 74.1nm; Be with adding surfactant and cosurfactant in the Oleum Rosae Rugosae, being titrated to even, transparent nano-emulsion system with the distilled water that is dissolved with quinapril hydrochloride.The hydrochloric quinapril of nano-emulsion that forms reaches more than 7.1%, and Oleum Rosae Rugosae reaches more than 9.4%.
2. quinapril hydrochloride of the present invention, Oleum Rosae Rugosae resisting hypertension nano-emulsion are evenly distributed, and transparent, the good stability of system has lower surface tension, has good flowability, taking convenience.
3. engulfed by reticuloendothelial cell rapidly after quinapril hydrochloride of the present invention, the administration of Oleum Rosae Rugosae resisting hypertension nano-emulsion; Make the rapid onset of medicine; And keep constant blood drug level and pharmacodynamics effect, and improve bioavailability of medicament, strengthen drug effect, reduce amount of drug and access times.
4. quinapril hydrochloride of the present invention, Oleum Rosae Rugosae resisting hypertension nano-emulsion efficacy stability, it is low to consume energy.
5. the present invention processes and can be made into oral liquid behind the nano-emulsion and directly take, also can seal or through processing such as lyophilized powder technology through capsule.
The specific embodiment
The inventor provides concrete method for preparing embodiment and uses the test of pesticide effectiveness to further specify the effect of medicine of the present invention.
Test Example 1 quinapril hydrochloride of the present invention, Oleum Rosae Rugosae nano-emulsion antihypertensive drug size are analyzed
The present invention detects through transmission electron microscope, and drop type of being is spherical, good dispersion, no adhesion.Detect its diameter Distribution between 50.9～95.7nm through the Ma Erwen Particle Size Analyzer, mean diameter is 74.1nm.
Test Example 2 quinapril hydrochlorides of the present invention, the stability analysis of Oleum Rosae Rugosae nano-emulsion antihypertensive drug
Whether through the stability that quinapril hydrochloride of the present invention, Oleum Rosae Rugosae nano-emulsion antihypertensive drug are observed in following centrifugal test, light stability test, temperature stability test etc., observing the present invention has layering, muddiness or crystal wild effect such as to separate out.
1. high speed centrifugation test
Get the quinapril hydrochloride of the present invention for preparing in right amount, Oleum Rosae Rugosae nano-emulsion antihypertensive drug in centrifuge tube; With centrifugal 10 min of the rotating speed of 15 000r/min; After the centrifugal test; Quinapril hydrochloride of the present invention, Oleum Rosae Rugosae nano-emulsion antihypertensive drug still keep the clear before centrifugal, wild effect such as do not see that layering, muddiness or crystal are separated out.
2. light stability test
The quinapril hydrochloride for preparing in right amount, Oleum Rosae Rugosae nano-emulsion antihypertensive drug are packed in transparent good colourless, the transparent vial, and sealing is positioned over 10d under the normal illumination condition, respectively at 1d, 2d, 4d, 6d, 8d, the 10d observation of taking a sample.The result shows that quinapril hydrochloride, the every duplicate samples of Oleum Rosae Rugosae nano-emulsion antihypertensive drug all keep clear, wild effect such as do not see that layering, muddiness or crystal are separated out.
3. temperature stability test
The quinapril hydrochloride for preparing in right amount, Oleum Rosae Rugosae nano-emulsion antihypertensive drug are packed in the good flint glass bottle of transparency, sealing, be positioned over 4 ℃, room temperature (25 ℃) with 40 ℃ three in keep sample under the temperature conditions and investigate each 30d, every at a distance from 5d sampling observation.The result shows that quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion antihypertensive drug all keep clear under these three kinds of temperature conditions, wild effect such as do not see that layering, muddiness or crystal are separated out.
4. long-term stable experiment
3 batches of nano-emulsions are sealed in the Brown Glass Brown glass bottles and jars only; Placed (25 ± 2) ℃, relative humidity (60 ± 5) % condition following 12 months; Respectively at 0,3,6,9 and time sampling in 12 months; Investigate the character and the changes of contents of nano-emulsion, and the list of references statistical analysis technique, the effect duration of calculating quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion antihypertensive drug.Result of the test is illustrated under the long term test condition, and the outward appearance of quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion antihypertensive drug keeps clear and bright, homogeneous always, does not see phenomenons such as layering, complexion changed, flocculation and breakdown of emulsion; Quinapril hydrochloride in the system and Oleum Rosae Rugosae content prolong in time and reduce gradually; The equation of linear regression that its content-time changing curve provides, the effect duration that calculates quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion antihypertensive drug is 38.27 months (is standard with time weak point person).
Test Example 3 rat tails manometrys are measured the drug effect (with Oleum Rosae Rugosae and the contrast of commercially available quinapril hydrochloride sheet) of quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion antihypertensive drug
40 of SHR rats are divided into 4 groups at random, 10 every group, are made as the quinapril hydrochloride sheet respectively; The Flos Rosae Rugosae line of oils; Quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion group and positive blank control group, first three groups give quinapril hydrochloride sheet suspension, Oleum Rosae Rugosae and quinapril hydrochloride, each 15mg/kgd of Oleum Rosae Rugosae nano-emulsion respectively, are dissolved in administration in the drinking-water; 1 time/d, continuous 12 weeks.10 of WKY rats are the normal control group, and 10 positive controls of SHR rat are not given medicine, normal drinking-water.
Measure and respectively organize rat arteria caudalis blood pressure.(before the medication) pressure measurement was 1 time when Mus was 6 weeks age, and blood pressure is surveyed in Mus 7 weeks of age (1 week after the medication) pressure measurement 1 time later on week about 1 time, finished up to experiment.The result sees table 1.
Table 1 respectively organize rat SBP comparison (x ± s, n=10)
| Group | Systolic pressure (mmHg) |
| Positive control | 197.8±10.4 |
| The quinapril hydrochloride sheet | 138.5±11.3 |
| Oleum Rosae Rugosae | 178.2±13.6 |
| Quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion | 130.2±8.1 |
| WKY normal control group | 126.3±8.9 |
The result shows; Quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion and positive controls, quinapril hydrochloride sheet and Flos Rosae Rugosae line of oils are relatively; Difference is all extremely remarkable; Show that quinapril hydrochloride not only can significantly reduce the blood pressure of positive rat, and antihypertensive effect and commercially available quinapril hydrochloride sheet compare effect with Oleum Rosae Rugosae more remarkable.
Test Example 4 toxicity tests
1. toxicological study project and conclusion:
Product of the present invention is in strict accordance with non-clinical safety evaluation methodology of new drug and commercially available quinapril hydrochloride tablet contrast having carried out acute toxicity test; Repeat administration toxicity test, genetic toxicity test (comprising Ames test, mouse bone marrow cells micronucleus test, the test of In vitro culture mammalian cell chromosome mutation), reproductive toxicity test (general reproductive toxicity test, sensitive period to teratogenic agent toxicity test, perinatal toxicity test), carcinogenic test, immunotoxicity test and local irritation test, result of the test is following.
These article are to chmice acute toxicity test conclusion: with commercially available quinapril hydrochloride tablet contrast, untoward reaction and death in measuring does not appear in quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion.
The result of genetic toxicity tests such as the Salmonella reversion test of product of the present invention, mouse sperm deformity test and testicular chromosome aberration test is all negative.
The result that rat 30d feeds product of the present invention shows: with commercially available quinapril hydrochloride tablet contrast; In experimental period; Each experimental group animal growth is good in quinapril hydrochloride, the metering of Oleum Rosae Rugosae nano-emulsion; All in normal range, histopathologic examination is no abnormality seen also for indexs such as body weight, food ration, routine blood test, blood biochemistry, organ coefficient.
These article long term toxicity test conclusion: with commercially available quinapril hydrochloride tablet contrast; In experimental period; In quinapril hydrochloride, the metering of Oleum Rosae Rugosae nano-emulsion; This medicine was not seen the rat untoward reaction in three months at continuous gastric infusion, and all in normal range, its main organs of pathologic finding and target organ do not see that all the toxic pathology that this guiding drug rises changes to each item inspection index.
Test Example 5 pharmacokinetics
Result of the test shows, after quinapril hydrochloride, Oleum Rosae Rugosae resisting hypertension nano-emulsion were oral, quinapril hydrochloride was absorbed and is hydrolyzed into active quinaprilat very soon, reaches peak value in 1 hour blood drug level of administration, and the half-life is 2 hours.Quinapril is mainly from RE, and 61% by homaluria, and 37% is drained by excrement.
Embodiment 1
Accurately take by weighing Oleum Rosae Rugosae 9.4g, EL40 25g and ethanol 5g and under room temperature (25 ℃) condition, stir, then to wherein slowly splashing into the distilled water that is dissolved with quinapril hydrochloride.Increase along with the distillation water yield; The system stickiness increases; When the amount that adds distilled water makes system become the oil-in-water type nano-emulsion by Water-In-Oil; The system viscosity is thinning from the most heavy-gravity state, and what produced this moment promptly is water white quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion, and the amount that add entry this moment is that 53.5g, quinapril hydrochloride are 7.1g.This ratio is the optimal proportion of quinapril hydrochloride, Oleum Rosae Rugosae resisting hypertension nano-emulsion.
Embodiment 2
Oleum Rosae Rugosae 10.7g, EL40 32g, 1,2-propylene glycol 4g, distilled water 51g, quinapril hydrochloride are 2.3g.
Embodiment 3
Oleum Rosae Rugosae 8.5g, RH40 20g, glycerin 10g, distilled water 54.2g, quinapril hydrochloride are 7.3g.
Embodiment 4
Oleum Rosae Rugosae 5.9g, RH40 16g, ethanol 8g, distilled water 61g, quinapril hydrochloride are 9.1g.
Embodiment 5
Oleum Rosae Rugosae 8.5g, Tween 80 27g, glycerin 3g, distilled water 54.2g, quinapril hydrochloride are 7.3g.
Embodiment 6
Oleum Rosae Rugosae 7.5g, Tween 80 21g, PEG400 7g, distilled water 56.6g, quinapril hydrochloride are 7.9g.
Embodiment 7
Oleum Rosae Rugosae 15g, EL40 20g, span80 10g, distilled water 50g, quinapril hydrochloride 5g.
Embodiment 8
Oleum Rosae Rugosae 10g, RH40 25g, span80 5g, distilled water 45g, 1,2-propylene glycol 5g, quinapril hydrochloride 10g.
Embodiment 9
Oleum Rosae Rugosae 5g, Tween 80 20g, span80 10g, distilled water 45g, PEG400 5g, quinapril hydrochloride 15g.
Embodiment 10
Oleum Rosae Rugosae 1g, poloxamer 188 22g, span80 5g, glycerin 5g, distilled water 49g, quinapril hydrochloride 18g.
Embodiment 11
Oleum Rosae Rugosae 20g, EL40 25g, distilled water 44g, PEG400 5g, glycerin 5g, quinapril hydrochloride 1g.
Claims (2)
1. a water bag type quinapril hydrochloride, Oleum Rosae Rugosae nano-emulsion antihypertensive drug is characterized in that its raw material and mass percent thereof are:
Quinapril hydrochloride 1%～18%
Surfactant 15%～40%
Cosurfactant 0～20%
Oleum Rosae Rugosae 1%～20%
All the other compositions are distilled water, and the mass percent sum of above-mentioned raw materials is 100%;
Described surfactant be in polyoxyl 40 hydrogenated castor oil, castor oil polyoxyethylene ether 40, Tween 80 or the poloxamer 188 any one or with the mixture of span80;
Described cosurfactant is a dehydrated alcohol, 1, the mixture of any one or a few in 2-propylene glycol, PEG400 or the glycerin.
2. quinapril hydrochloride according to claim 1, Oleum Rosae Rugosae nano-emulsion antihypertensive drug is characterized in that the particle diameter of this medicine is between 50.9～95.7nm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101635258A CN102698245A (en) | 2012-05-24 | 2012-05-24 | Antihypertensive drug of quinapril hydrochloride and rose oil nanoemulsion |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101635258A CN102698245A (en) | 2012-05-24 | 2012-05-24 | Antihypertensive drug of quinapril hydrochloride and rose oil nanoemulsion |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102698245A true CN102698245A (en) | 2012-10-03 |
Family
ID=46891492
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101635258A Pending CN102698245A (en) | 2012-05-24 | 2012-05-24 | Antihypertensive drug of quinapril hydrochloride and rose oil nanoemulsion |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102698245A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106138085A (en) * | 2015-03-25 | 2016-11-23 | 烟台宝备生物技术有限公司 | A kind of have medicine or the health food increasing bone density effect |
-
2012
- 2012-05-24 CN CN2012101635258A patent/CN102698245A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106138085A (en) * | 2015-03-25 | 2016-11-23 | 烟台宝备生物技术有限公司 | A kind of have medicine or the health food increasing bone density effect |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW201114766A (en) | Pharmaceutical composition for a hepatitis C viral protease inhibitor | |
| KR20140041504A (en) | Transdermal compositions of ibuprofen and methods of use thereof | |
| WO2022160971A1 (en) | Concentrate containing poorly soluble drug, and emulsion prepared therefrom | |
| CN102631405A (en) | Compound apigenin nanoemulsion antihypertensive drug | |
| CN101703468A (en) | Nano-emulsion of vitamin E oil and preparation method thereof | |
| CN104352566A (en) | Oil-in-water compound chlortetracycline nanoemulsion | |
| CN111643451B (en) | Honokiol self-emulsifying microemulsion preparation for injection and preparation method thereof | |
| CN104274826B (en) | A kind of oil-in-water type compound colistin nano-emulsion | |
| CN104027390A (en) | Oil-in-water type compound amphotericin B nano-emulsion | |
| JP2021523195A (en) | HC-1119 formulation and its manufacturing method and use | |
| CN102698245A (en) | Antihypertensive drug of quinapril hydrochloride and rose oil nanoemulsion | |
| CN105997873A (en) | Oil-in-water type terazosin nanoemulsion antihypertensive drug | |
| CN102727721A (en) | Benazepril hydrochloride-hyacinth oil nanoemulsion antihypertensive drug | |
| CN102697856A (en) | Trimetaphan camsilate and linseed oil nanoemulsion antihypertensive drug | |
| CN102657697A (en) | Propranolol-eugenol type basil oil nano-emulsion medicament and preparation method thereof | |
| CN102716158A (en) | In-water type mecamylamine and celery seed oil nanoemulsion antihypertensive medicine | |
| CN102727670A (en) | Oil-in-water type terazosin-grape seed oil antihypertensive drug | |
| CN102727608A (en) | Nadolol-apple seed oil nanoemulsion antihypertensive drug | |
| CN102716163A (en) | Pargyline and asarum oil nanoemulsion antihypertensive medicine | |
| CN102698246A (en) | Antihypertensive drug of enalapril and safflower oil nanoemulsion | |
| CN104352554B (en) | A kind of compound Cefquinome antibacterials | |
| CN102727862A (en) | Delapril hydrochloride-Chuanxiong oil nanoemulsion antihypertensive drug | |
| CN102716185A (en) | Oil-in-water celiprolol and cassia oil nano emulsion antihypertensive medicine | |
| CN102727727A (en) | Oil-in-water type sodium nitroprusside-garlic oil nanoemulsion antihypertensive drug | |
| CN102697852A (en) | Hydrochloric acid cicletanine and cinnamon oil nanoemulsion antihypertensive drug |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20121003 |