CN108593796A - A method of detection bulk pharmaceutical chemicals Austria is uncommon for organic residual solvent in Buddhist nun - Google Patents
A method of detection bulk pharmaceutical chemicals Austria is uncommon for organic residual solvent in Buddhist nun Download PDFInfo
- Publication number
- CN108593796A CN108593796A CN201810377654.4A CN201810377654A CN108593796A CN 108593796 A CN108593796 A CN 108593796A CN 201810377654 A CN201810377654 A CN 201810377654A CN 108593796 A CN108593796 A CN 108593796A
- Authority
- CN
- China
- Prior art keywords
- uncommon
- buddhist nun
- dichloromethane
- acetonitrile
- organic
- 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
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N2030/042—Standards
- G01N2030/045—Standards internal
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention belongs to Pharmaceutical Analysis detection fields, relate to a kind of uncommon method for organic solvent residual in Buddhist nun of detection bulk pharmaceutical chemicals Austria, the uncommon method for ethyl alcohol, acetonitrile, ethyl acetate, dichloromethane, Isosorbide-5-Nitrae dioxane residual quantity in Buddhist nun difficult to understand is detected simultaneously with capillary gas chromatography more particularly, to a kind of.This method N, N dimethylformamides are as solvent, nitrogen is as carrier gas, weak polarity capillary column is chromatographic column, input mode is direct injected, using temperature programming pattern, each ingredient can be made to realize baseline separation, using the uncommon content for ethyl alcohol, acetonitrile, ethyl acetate, 5 kinds of dichloromethane, Isosorbide-5-Nitrae dioxane organic solvents in Buddhist nun of internal mark method determination Austria.The method of the present invention high sensitivity, easy to operate, accuracy is high, is suitble to while measuring the uncommon organic residual solvent in Buddhist nun difficult to understand.
Description
Technical field
The invention belongs to Pharmaceutical Analysis detection fields, and in particular to a kind of detection bulk pharmaceutical chemicals Austria is uncommon molten for organic residue in Buddhist nun
The assay method of agent.
Background technology
Ao Xi replaces Buddhist nun (Osimertinib) also known as AZD-9291, the entitled N- { 2- { [2- (dimethylamino) ethyl] of chemistry
(methyl) amino } -4- methoxyl groups -5- { [4- (l- methyl-lH-indol -3- bases) pyrimidine -2-base] amino } phenyl) 2 alkene acyl of propyl-
Amine is the oral anticarcinogen researched and developed by Britain's AstraZeneca, for treating the positive non-small cell of metastatic EGFR T790M mutation
Lung cancer.The medicine is a kind of irreversible and Catastrophic selection EGF-R ELISA (EGFR) tyrosine kinase inhibitor,
IC50 is respectively 12.92,11.44 and 493.8nM.Compared to conventional medicament, Austria is uncommon significant in efficacy for Buddhist nun, and tolerance is good, and pair is made
It is a kind of to have very much promising drug with lower.
About the uncommon research for Buddhist nun's residual solvent difficult to understand, have no that domestic and foreign literature is reported at present.It is difficult to understand uncommon in Buddhist nun in order to control
The content of residual solvent, it is ensured that its safety causes damages to health to prevent its residual solvent, and the present invention is replaced for difficult to understand wish
5 kinds of ethyl alcohol, acetonitrile, ethyl acetate, dichloromethane, the Isosorbide-5-Nitrae-dioxane organic solvent residuals introduced by synthesis technology in Buddhist nun,
Detect the content of this 5 kinds of organic solvents simultaneously using gas chromatography.This method high sensitivity, easy to operate, accuracy is high, steady
It is qualitative good, it can be used for quantitative determining the uncommon residual solvent in Buddhist nun difficult to understand.
Invention content
It is an object of the invention to simplicity, quickly and accurately analysis Austria wishes for the organic solvent residual in Buddhist nun's bulk pharmaceutical chemicals, carries
For a kind of drug quality detection technique with universality.The technical problem to be solved by the present invention is to same using gas-chromatography
When the detection content for ethyl alcohol, acetonitrile, ethyl acetate, dichloromethane, 1,4- dioxane in Buddhist nun difficult to understand uncommon.
The present invention solves above-mentioned technical problem by following technical proposal.
A method of detection is difficult to understand uncommon for organic residual solvent in Buddhist nun, is detected simultaneously with gas chromatography difficult to understand uncommon for second in Buddhist nun
The content of alcohol, acetonitrile, ethyl acetate, dichloromethane, Isosorbide-5-Nitrae-dioxane, the specific steps are：
(1) using n,N-Dimethylformamide as solvent sample dissolution, and proper amount of methanol solution is added as internal standard.
(2) sample solution that step (1) is obtained, is detected through capillary gas chromatography, obtains containing for organic solvent residual
Amount.
A kind of gas-chromatography accurate measuring method of organic solvent residual：The poly- carbon siloxanes column of 5% phenyl is selected, with direct
The mode sample introduction of sample introduction, is monitored with hydrogen ion flame detector, temperature programming pattern, carries out sample measurement.
Preferably, it is 30m × 0.32mm × 0.25 μm that chromatographic column, which selects Thermo TG-5MS columns, specification,；It is to carry with nitrogen
Gas；Injector temperature is 200-250 DEG C, and detector temperature is 230-260 DEG C；Carrier gas is inert gas, using shunt mode；Journey
Sequence heating mode：Temperature range is 30-150 DEG C, and heating rate is 15 DEG C of min-1；Sampling volume：1μL；Input mode：Directly
Sample introduction.
It is highly preferred that injector temperature is 250 DEG C；Detector temperature is 250 DEG C；Carrier gas is nitrogen.
It is highly preferred that starting column temperature keeps 10min, terminal column temperature to keep 4min.
The advantage of the invention is that：
(1) it uses gas chromatography to detect ethyl alcohol, acetonitrile, ethyl acetate, dichloromethane, 1,4- dioxane simultaneously to contain
Amount, high sensitivity is reproducible, and precision is high；
(2) present invention is suitble to difficult to understand uncommon remaining for ethyl alcohol, acetonitrile, ethyl acetate, dichloromethane, 1,4- dioxane in Buddhist nun
Detection.
Description of the drawings
Fig. 1 is blank solvent chromatogram of the present invention
Fig. 2 is surveyed ethyl alcohol, acetonitrile, ethyl acetate, dichloromethane, 1,4- dioxane mixed reference substance solutions by the present invention
Chromatogram (1：Methanol, 2：Ethyl alcohol, 3：Acetonitrile, 4：Ethyl acetate, 5：Dichloromethane, 6：1,4- dioxane)
Fig. 3 is that the present invention is difficult to understand uncommon for Buddhist nun's test solution chromatogram (1：Methanol, 2：Ethyl alcohol, 5：Dichloromethane)
Specific implementation mode
In order to make those skilled in the art more fully understand technical scheme of the present invention, it will further pass through example below
It is stated.
The required reagent of the present invention is commercially available.
Embodiment 1
1 instrument and reagent
Instrument：Sai Mo flies generation that 1300 gas chromatographs of Trace；
Reagent：Bulk pharmaceutical chemicals Austria is uncommon, and for Buddhist nun, (lot number 20161222,20161223,20161224, is carried by A pharmaceutical Co. Ltds
For), methanol, acetonitrile (chromatographically pure, TEDIA companies of the U.S.), ethyl alcohol, ethyl acetate (analyzing pure, TEDIA companies of the U.S.), dichloro
Methane, Isosorbide-5-Nitrae-dioxane (analyzing pure, Sinopharm Chemical Reagent Co., Ltd.), n,N-Dimethylformamide (chromatographically pure, on
Extra large Aladdin biochemical technology limited liability company).
2 chromatographic conditions
Chromatographic column：Thermo TG-5MS, specification are 30m × 0.32mm × 0.25 μm；
Injector temperature：250℃；
Detector temperature：250℃；
Carrier gas is nitrogen, split ratio 10:1；
Temperature programming：It is 30 DEG C to originate column temperature, 10min is kept, later with 15 DEG C of min-1Rate rise to 150 DEG C, protect
Hold 4min；
Sampling volume：1μL；
Input mode：Direct injected；
3 solution are prepared
3.1 reference substance storing solutions
Precision weighs ethyl alcohol, acetonitrile, ethyl acetate, dichloromethane and each 50.0mg of Isosorbide-5-Nitrae-dioxane, is placed in 50mL appearances
In measuring bottle, n,N-Dimethylformamide is added, is settled at 50mL scales, is mixed uniformly, as mixing reference substance deposit
Liquid.
3.2 internal standard storing solutions
It weighs methanol 1.0g to be placed in 50ml volumetric flasks, n,N-Dimethylformamide is added, is settled at 50mL scales, it will
It is uniformly mixed, and obtains 20.0mgmL-1Methanol solution.It is accurate again to draw 20.0mgmL-1Methanol solution 2.5mL is placed in
In 100mL volumetric flasks, it is diluted at 100mL scales with n,N-Dimethylformamide.
3.3 reference substance solution
Precision measures 5.0mL reference substance storing solutions and is placed in 50mL volumetric flasks, adds 10.0mL internal standard methanol storing solutions, with
N,N-Dimethylformamide dilutes and is settled to scale to get reference substance solution.
3.4 test solution
Precision weighs that 3 batches of bulk pharmaceutical chemicals Austria are uncommon to be placed in for each 20.0mg of Buddhist nun in 5mL volumetric flasks, respectively in accurate addition 1.0mL
Methanol storing solution is marked, addition n,N-Dimethylformamide is appropriate, and ultrasonic dissolution is settled at scale, is mixed uniformly.
4 samples measure
(1) system suitability
Precision measures ethyl alcohol, acetonitrile, 1 μ L of ethyl acetate, dichloromethane and Isosorbide-5-Nitrae-dioxane mixed reference substance solution, into
Sample records chromatogram.
Each component can be detached preferably under above-mentioned chromatographic condition, and the theoretical cam curve at each peak is all higher than 50
000, each adjacent peak is realized and is kept completely separate, and in 0.95~1.05 range, peak sequence is followed successively by tailing factor：Methanol, second
Alcohol, acetonitrile, ethyl acetate, dichloromethane, Isosorbide-5-Nitrae-dioxane.Chromatogram refers to attached drawing 2.
(2) quantitative limit and detection limit measure
Reference substance storing solution is diluted using gradually dilution method, 1 μ L of sample introduction calculate detection limit, with letter with signal-to-noise ratio S/N=3
It makes an uproar and calculates quantitative limit than S/N=10.The detection of ethyl alcohol, acetonitrile, ethyl acetate, dichloromethane and 1,4- dioxane, which limits, is respectively
0.68,1.23,2.81,1.81 and 2.93 μ gmL-1(S/N=3), quantitative limit is respectively 1.68,3.76,9.48,3.38 and
9.54μg·mL-1(S/N=10).The result shows that ethyl alcohol, acetonitrile, ethyl acetate, dichloromethane and Isosorbide-5-Nitrae-dioxane detection limit
The uncommon measurement requirement for residual solvent in Buddhist nun difficult to understand can be met with quantitative limit test result.
(3) precision test
It takes mixed reference substance solution sample introduction six times, records ethyl alcohol, acetonitrile, ethyl acetate, dichloromethane and Isosorbide-5-Nitrae-two respectively
Then the peak area (As) of six ring chromatographic peak area (Ar) of oxygen and internal standard methanol calculates the RSD values of the two ratio, respectively
2.14%, 2.39%, 2.82%, 2.13% and 2.38% (n=6), RSD value meet the requirements, and show that instrument precision is good.
(4) linear test
Diluted 1 μ L of serial standards solution sample introduction are taken, 5 kinds of solvent peak areas (Ar) and internal standard methanol peak area are recorded
(As), with the ratio of the two (Y=Ar/As) for ordinate, the mass concentration [ρ/(μ gmL of 5 kinds of residual solvents-1)] it is horizontal seat
Mark carries out linear regression.Regression equation and related coefficient the results are shown in Table 1.
The uncommon equation of linear regression and related coefficient (n=5) for 5 kinds of residual solvents of Buddhist nun difficult to understand of table 1
(5) recovery test
It takes bulk pharmaceutical chemicals Austria of each residual solvent levels known to 9 parts is uncommon to replace Buddhist nun, basic, normal, high concentration test solution is added, into
1 μ L of sample, record ethyl alcohol, acetonitrile, ethyl acetate, dichloromethane and Isosorbide-5-Nitrae-dioxane chromatographic peak peak area (Ar) and internal standard first
The peak area (As) of alcohol calculates the rate of recovery, the results are shown in Table 2.
Table 2 is difficult to understand uncommon for 5 kinds of residual solvent sample recovery rates (n=9) in Buddhist nun
(6) stability test
It takes 6 parts of same a collection of bulk pharmaceutical chemicals Austria are uncommon to replace Buddhist nun, prepares 6 parts of test solutions, respectively placement 0,2,4,6,8,10h, sample introduction 1
μ L record the peak area (As) of 5 kinds of solvent chromatographic peak peak areas (Ar) and internal standard methanol, calculate the RSD of ratio between the two
Value, alcohol stability RSD are 4.3%, and ethyl acetate stability RSD is 1.07%, acetonitrile, dichloromethane and Isosorbide-5-Nitrae-dichloromethane
It is not detected.The result shows that west difficult to understand can stablize placement 10h at room temperature for Buddhist nun's test solution.
(7) sample measurement result
It takes 3 batches of bulk pharmaceutical chemicals Austria are uncommon to replace Buddhist nun (lot number 20161222,20161223 and 20161224) each 20mg, prepares molten for trying
3 parts of liquid, 1 μ L of sample introduction calculate content with internal standard method, and as a result west difficult to understand the results are shown in Table 3 for solvent residual amount in 3 batches of samples of Buddhist nun.
Replace the assay result of residual solvent in Buddhist nun in the west difficult to understand of table 3
Finally it should be noted that：To those of ordinary skill in the art, in the premise for not departing from the principle of the invention
Under, the present invention can also be made improvements and modifications, all within the spirits and principles of the present invention, any modification for being done, etc.
With replacement, improvement etc., should also fall into the protection domain of the claims in the present invention.
Claims (8)
1. a kind of detection uncommon method for organic residual solvent in Buddhist nun difficult to understand, it is characterised in that：
(1) detection cycle 22min；
(2) while 5 kinds of organic residual solvents being measured；
(3) organic residual solvent described in is ethyl alcohol, acetonitrile, ethyl acetate, dichloromethane, 1,4- dioxane；
(4) gas chromatography is used to detect, direct injected is measured difficult to understand uncommon for 5 kinds of organic principles in Buddhist nun simultaneously using internal standard method
Content.
2. detection method according to claim 1, which is characterized in that the chromatographic column is weak polarity capillary column, carrier gas
For inert gas, injector temperature is 200-250 DEG C, and detector temperature is 230-260 DEG C.
3. the detection method according to claims 1 or 2, which is characterized in that chromatographic column is the poly- carbon siloxanes of 5% phenyl
Column.
4. the detection method according to claims 1 or 2, which is characterized in that carrier gas is nitrogen.
5. detection method according to claim 1, which is characterized in that use temperature programming pattern：Temperature range is 30-
150℃。
6. detection method according to claim 5, which is characterized in that heating rate is 15 DEG C of min-1。
7. detection method according to claim 1, which is characterized in that sampling volume is 1 μ L.
8. detection method according to claim 1, which is characterized in that 5 kinds of organic principles be ethyl alcohol, acetonitrile, ethyl acetate,
Dichloromethane, 1,4- dioxane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810377654.4A CN108593796A (en) | 2018-04-25 | 2018-04-25 | A method of detection bulk pharmaceutical chemicals Austria is uncommon for organic residual solvent in Buddhist nun |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810377654.4A CN108593796A (en) | 2018-04-25 | 2018-04-25 | A method of detection bulk pharmaceutical chemicals Austria is uncommon for organic residual solvent in Buddhist nun |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108593796A true CN108593796A (en) | 2018-09-28 |
Family
ID=63609093
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810377654.4A Pending CN108593796A (en) | 2018-04-25 | 2018-04-25 | A method of detection bulk pharmaceutical chemicals Austria is uncommon for organic residual solvent in Buddhist nun |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108593796A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113740456A (en) * | 2021-09-03 | 2021-12-03 | 广东省中鼎检测技术有限公司 | Detection method for testing 1, 4-dioxane in consumer product |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2842614A1 (en) * | 2013-08-30 | 2015-03-04 | Biotage AB | Sample preparation method for analysis of acrylamide |
| CN104820041A (en) * | 2015-05-14 | 2015-08-05 | 中唯炼焦技术国家工程研究中心有限责任公司 | Method for analyzing residual organic solvents in fluorene derivatives |
| CN105136921A (en) * | 2015-08-14 | 2015-12-09 | 河南师范大学 | Method for measuring content of (4R,6R) -6-aminoethyl-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate |
| CN105388223A (en) * | 2015-10-13 | 2016-03-09 | 杭州华东医药集团新药研究院有限公司 | Detection method for decitabine impurities |
| CN106749402A (en) * | 2016-11-25 | 2017-05-31 | 厦门大学 | A kind of cold labeling chiral phosphorus reagent and preparation method and application |
-
2018
- 2018-04-25 CN CN201810377654.4A patent/CN108593796A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2842614A1 (en) * | 2013-08-30 | 2015-03-04 | Biotage AB | Sample preparation method for analysis of acrylamide |
| CN104820041A (en) * | 2015-05-14 | 2015-08-05 | 中唯炼焦技术国家工程研究中心有限责任公司 | Method for analyzing residual organic solvents in fluorene derivatives |
| CN105136921A (en) * | 2015-08-14 | 2015-12-09 | 河南师范大学 | Method for measuring content of (4R,6R) -6-aminoethyl-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate |
| CN105388223A (en) * | 2015-10-13 | 2016-03-09 | 杭州华东医药集团新药研究院有限公司 | Detection method for decitabine impurities |
| CN106749402A (en) * | 2016-11-25 | 2017-05-31 | 厦门大学 | A kind of cold labeling chiral phosphorus reagent and preparation method and application |
Non-Patent Citations (3)
| Title |
|---|
| PURANIK S.B 等: "HEAD SPACE GAS CHROMATOGRAPHY ANALYSIS OF RESIDUALSOLVENTS BY USING EC-5 COLUMN", 《INTERNATIONAL JOURNAL OF PHARMACEUTICAL CHEMISTRY RESEARCH》 * |
| ROUHOLLAH HEYDARI 等: "RESIDUAL SOLVENTS DETERMINATION IN PHARMACEUTICALS BY STATIC HEADSPACE-GAS CHROMATOGRAPHY AND HEADSPACE LIQUID-PHASE MICROEXTRACTION GAS CHROMATOGRAPHY", 《ANALYTICAL LETTERS》 * |
| 胡建国 等: "毛细管气相色谱法测定奥美沙坦酯中14种有机溶剂的残留量", 《药学实践杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113740456A (en) * | 2021-09-03 | 2021-12-03 | 广东省中鼎检测技术有限公司 | Detection method for testing 1, 4-dioxane in consumer product |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103487519B (en) | A kind of detect the method for multiple residual solvent in medicine | |
| Ingale et al. | Advance approaches for the impurity profiling of pharmaceutical drugs: A review. | |
| CN115453012A (en) | Reverse phase HPLC method for simultaneously determining multiple positional isomers in vortioxetine hydrobromide | |
| CN108982695A (en) | The method that derivatization HPLC method measures azido compound in drug or in which mesosome | |
| CN105136921B (en) | Method for measuring content of (4R,6R) -6-aminoethyl-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate | |
| CN108593796A (en) | A method of detection bulk pharmaceutical chemicals Austria is uncommon for organic residual solvent in Buddhist nun | |
| CN109856255A (en) | A kind of analysis method for the isomer impurities content controlling ticagrelor intermediate | |
| CN109975435A (en) | The measuring method of isopropyl mesylate content in a kind of safinamide | |
| CN100480698C (en) | Method for inspecting hypotensive medicine | |
| CN109799298A (en) | Detection method in relation to substance in a kind of pyrrole Lun Panai bulk pharmaceutical chemicals | |
| CN114324703B (en) | Method for simultaneously detecting multiple amino acids | |
| CN110208432A (en) | The detection method of residual chlorine propenyl in a kind of drug | |
| CN106896162B (en) | A kind of HPLC method of impurity in detection meloxicam tablet | |
| CN108387653A (en) | A kind of method of ethanol content in measurement industrial methanol | |
| CN108872416A (en) | A kind of method of simultaneous quantitative detection erucyl amide and ethylene bis stearamide | |
| CN111077245B (en) | UPLC characteristic spectrum establishing method and detection method of radix semiaquilegiae medicinal material | |
| CN114280191A (en) | Method for detecting related substances in bis-cysteine and preparation thereof | |
| CN115343399B (en) | Method for detecting residual solvent of N-alkyl pyrrolidone in bulk drug | |
| CN107490629A (en) | A kind of HPLC analytical method of afatinib intermediate | |
| CN113406236B (en) | Method for detecting impurities in 1- (3-pyridyl) -3- (dimethylamino) -2-propylene-1-ketone | |
| CN107966498B (en) | Method for detecting solvent residue in Idelalis | |
| CN114200067B (en) | High performance liquid chromatography analysis method for 6-bromo-3-hydroxy pyrazine-2-carboxamide and impurities | |
| CN108344813A (en) | The method that HPLC-CAD measures sodium content in Dextrose and Sodium Chloride Inj. | |
| CN108107138A (en) | The method that HPLC-CAD measures glucose in Dextrose and Sodium Chloride Inj. | |
| CN108548872A (en) | 1- in a kind of Dasatinib（2- ethoxys）The detection method of piperazine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180928 |