CN105699555B - A kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene - Google Patents
A kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene Download PDFInfo
- Publication number
- CN105699555B CN105699555B CN201610173909.6A CN201610173909A CN105699555B CN 105699555 B CN105699555 B CN 105699555B CN 201610173909 A CN201610173909 A CN 201610173909A CN 105699555 B CN105699555 B CN 105699555B
- Authority
- CN
- China
- Prior art keywords
- ethoxy
- hydroxy
- propenyl benzene
- acetonitrile
- preparation
- 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.)
- Expired - Fee Related
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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- 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
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
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)
- Spectroscopy & Molecular Physics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
Abstract
The invention discloses a kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene, include the preparation of test solution：The sample containing 1-ethoxy-2-hydroxy-4-propenyl benzene is taken, acetonitrile is dissolved in, through 0.22 μm or 0.45 μm of membrane filtration, obtains test solution；It is prepared by liquid chromatogram：Test solution is prepared through liquid chromatogram, mobile phase is acetonitrile water or methanol-water, and flow rate of mobile phase is 80~100mLmin‑1, type of elution is gradient elution, and Detection wavelength 254nm, stationary phase reverse phase C18 fillers, 10 μm of filler particle size, 0.5 1.5ml of sample size, operation temperature is 30 DEG C, collects the fraction of 16.5 20.8min.Present invention process is simple and convenient to operate, separating rate is fast, and the 1-ethoxy-2-hydroxy-4-propenyl benzene purity height of preparation, product purity can reach 99.41%, and product quality is stablized, and uniformity is good, mobile phase recoverable, pollution-free.
Description
Technical field
The present invention relates to a kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene, belong to compound extraction purification
Field.
Background technology
In recent years, as the raising of the food-safe requirement of people and analysis detection, quality control are to a variety of sterling demands
Increase, the Study on Preparation Technology of various one pack system sterlings is also more and more extensive.Preparative liquid chromatography technology as it is a kind of from
The important method that different component is detached in complex compound, with quick, efficient, easy to operate, product purity is high, batch processing amount
The advantages that larger, the favor of more and more segregated detection worker.
1-ethoxy-2-hydroxy-4-propenyl benzene (2-Ethoxy-5- (1-propenyl)-phenol) alias vanitrope, appearance
For white powder crystal, 86-88 DEG C of fusing point, boiling point 312.8 ± 30.0 DEG C (760Torr), pKa10.02 ± 0.10 (25 DEG C) are close
1.052 ± 0.06g/cm3 is spent, water is slightly soluble in, in ethanol molten 10%, molten 4% in propylene glycol, molten 20% in benzylalcohol.It
With strong and lasting cloves and vanilla fragrance, it is widely used in the food such as candy, beverage, ice cream as flavorant
Market.It is mainly used as vanillic aldehyde substitute and prepares chocolate essence.1-ethoxy-2-hydroxy-4-propenyl benzene is as thio-alcohol fragrance
Other Sulfur-containing flavor important intermediates are synthesized, are mostly the micro constitutent of food, content is 10 in food-6Or 10-9Grade.It
Fragrance use is can be used as, synergist is alternatively arranged as and antioxidant uses, quality safety monitoring belongs to day-to-day supervision model
It encloses.Therefore, a kind of simple, the quick separating preparation method of 1-ethoxy-2-hydroxy-4-propenyl benzene how are researched and developed, for the production of the substance
And it using reference frame is provided, becomes as technical problem urgently to be resolved hurrily.
Invention content
The technical problem to be solved by the present invention is to overcome the existing defects, provides a kind of 1-ethoxy-2-hydroxy-4-propenyl benzene
Method for preparing liquid chromatography, this method is easy to operate, and DNA purity is high.
In order to solve the above technical problem, the present invention provides the following technical solutions：
A kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene, including following steps：
(1) preparation of test solution：The sample containing 1-ethoxy-2-hydroxy-4-propenyl benzene is taken, is dissolved in acetonitrile or methanol, is passed through
0.22 μm or 0.45 μm of membrane filtration, obtain test solution；
(2) prepared by liquid chromatogram：Test solution obtained by step (1) is prepared through liquid chromatogram, wherein chromatography
Condition is：Mobile phase is acetonitrile-water or methanol-water, and flow rate of mobile phase is 80~100mLmin-1, type of elution washes for gradient
De-, Detection wavelength 254nm, stationary phase is reverse phase C18 fillers, and filler particle size is 10 μm, sample size 0.5-1.5ml, operation
Temperature is 30 DEG C, collects the fraction of 18.5-19.5min, obtains 1-ethoxy-2-hydroxy-4-propenyl benzene.
UV detector or diode array detector can be used in detector of the present invention.
It is preferably in the above scheme, chromatographic column is Venusil XBP C18,10 μm of filler particle size, apertureColor
Compose column dimension 50*250mm.
In any of the above-described scheme preferably, the gradient of elution is 0-30min：- 75% acetonitrile of 50% acetonitrile.
In any of the above-described scheme preferably, the gradient of elution is 0-30min：- 75% methanol of 50% methanol.
In any of the above-described scheme preferably, sample size 1ml, flow velocity 80ml/min, separating degree is best at this time,
The preparation of 1-ethoxy-2-hydroxy-4-propenyl benzene sample can be completed in 30min, product purity reaches 99.41%.
In any of the above-described scheme preferably, the fraction of 19min is collected.The purity of product is high at this time.
In any of the above-described scheme preferably, the fraction of collection is received in the outer wall package masking foil of advance nitrogen filling
Brown bottle in, first under the state that is protected from light blow away a small amount of acetonitrile with nitrogen, be then directly lyophilized in freeze dryer, obtain dry third
Alkenyl guaethol.
Fraction is stored in the brown bottle of outer wall package masking foil of nitrogen filling, external condition can be prevented to propylene
The destruction of base guaethol.
Beneficial effects of the present invention：The 1-ethoxy-2-hydroxy-4-propenyl benzene purity prepared through the invention is high, can be with performing an analysis
The standard items of detection.The method and process of the present invention is simple and convenient to operate, separating rate is fast, the acrylic ethyl guaiaci lignum of preparation
Phenol purity is high, product purity can reach 99.41%, and product quality is stablized, and uniformity is good, mobile phase recoverable, pollution-free,
Realize clean manufacturing.
Description of the drawings
Fig. 1 is the infrared spectrogram of 1-ethoxy-2-hydroxy-4-propenyl benzene；
Fig. 2 is the UV-vis absorption spectrum figure of 1-ethoxy-2-hydroxy-4-propenyl benzene；
Fig. 3 is the first mass spectrometric figure of 1-ethoxy-2-hydroxy-4-propenyl benzene；
Fig. 4 is the second order ms figure of 1-ethoxy-2-hydroxy-4-propenyl benzene；
Fig. 5 is 1-ethoxy-2-hydroxy-4-propenyl benzene1H-NMR spectrum；
Fig. 6 is 1-ethoxy-2-hydroxy-4-propenyl benzene13C-NMR spectrograms.
Specific implementation mode
Hereinafter, preferred embodiments of the present invention will be described, it should be understood that preferred embodiment described herein is only used
In the description and interpretation present invention, it is not intended to limit the present invention.
1-ethoxy-2-hydroxy-4-propenyl benzene sample in the present invention can purchase in Aladdin company, be industrial products.
Embodiment 1：
A kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene, including following steps：
(1) preparation of test solution：The sample containing 1-ethoxy-2-hydroxy-4-propenyl benzene is taken, acetonitrile is dissolved in, is filtered through 0.45 μm
Membrane filtration obtains test solution；
(2) prepared by liquid chromatogram：The 1-ethoxy-2-hydroxy-4-propenyl benzene of high-purity, wherein color are obtained using preparative liquid chromatography
Spectral condition is：Chromatographic column be Venusil XBP C18 (10 μm,50*250mm), mobile phase is acetonitrile and water, mobile phase
Flow velocity is 80mLmin-1, gradient 0-30min：- 75% acetonitrile of 50% acetonitrile (v/v), Detection wavelength 254nm, sample size
1ml, operation temperature are 30 DEG C, collect the fraction of 19min or so；
(3) it collects：Fraction is received in the brown bottle of outer wall package masking foil of advance nitrogen filling, is first being protected from light shape
A small amount of acetonitrile is blown away with nitrogen under state, is then directly lyophilized in freeze dryer, dry 1-ethoxy-2-hydroxy-4-propenyl benzene is obtained.
The preparation of sample is completed in 30min, product purity reaches 99.41%.
The infrared spectrogram such as Fig. 1 for the 1-ethoxy-2-hydroxy-4-propenyl benzene monomer that the present embodiment obtains, ultraviolet-visible absorption
Spectrum is shown in that Fig. 2, first mass spectrometric are shown in that Fig. 3, second order ms are shown in Fig. 4,1H-NMR spectrums are shown in Fig. 5,13C-NMR spectrums are shown in that Fig. 6, wherein nuclear-magnetism are surveyed
Examination is with CDCl3For solvent.
Embodiment 2：
A kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene, including following steps：
(1) preparation of test solution：1-ethoxy-2-hydroxy-4-propenyl benzene sample is weighed, acetonitrile is dissolved in, through 0.45um filter membranes
Filtering, obtains sample solution；
(2) prepared by liquid chromatogram：The 1-ethoxy-2-hydroxy-4-propenyl benzene of high-purity, wherein color are obtained using preparative liquid chromatography
Spectral condition is：Chromatographic column be Venusil XBP C18 (10 μm,50*250mm), mobile phase is acetonitrile and water, mobile phase
Flow velocity is 90mLmin-1, gradient 0-30min：- 75% acetonitrile of 50% acetonitrile (v/v), Detection wavelength 254nm, sample size
0.5ml, operation temperature are 30 DEG C, collect the fraction of 19min or so.
(3) it collects：Fraction is received in the brown bottle of outer wall package masking foil of advance nitrogen filling, is first being protected from light shape
A small amount of acetonitrile is blown away with nitrogen under state, is then directly lyophilized in freeze dryer, dry 1-ethoxy-2-hydroxy-4-propenyl benzene is obtained.
The preparation of sample is completed in 30min, product purity reaches 99.39%.
Embodiment 3：
A kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene, including following steps：
(1) preparation of test solution：1-ethoxy-2-hydroxy-4-propenyl benzene sample is weighed, acetonitrile is dissolved in, through 0.45um filter membranes
Filtering, obtains test solution；
(2) prepared by liquid chromatogram：The 1-ethoxy-2-hydroxy-4-propenyl benzene of high-purity, wherein color are obtained using preparative liquid chromatography
Spectral condition is：Chromatographic column be Venusil XBP C18 (10 μm,50*250mm), mobile phase is acetonitrile and water, mobile phase
Flow velocity is 100mLmin-1, gradient 0-30min：- 75% acetonitrile of 50% acetonitrile (v/v), Detection wavelength 254nm, sample size
1.5ml, operation temperature are 30 DEG C, collect the fraction of 19min or so；
(3) it collects：Fraction is received in the brown bottle of outer wall package masking foil of advance nitrogen filling, is first being protected from light shape
A small amount of acetonitrile is blown away with nitrogen under state, is then directly lyophilized in freeze dryer, dry 1-ethoxy-2-hydroxy-4-propenyl benzene is obtained.
The preparation of sample is completed in 30min, product purity reaches 99.38%.
Embodiment 4
A kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene, including following steps：
(1) preparation of test solution：1-ethoxy-2-hydroxy-4-propenyl benzene sample is weighed, methanol is dissolved in, through 0.45um filter membranes
Filtering, obtains test solution；
(2) prepared by liquid chromatogram：The 1-ethoxy-2-hydroxy-4-propenyl benzene of high-purity, wherein color are obtained using preparative liquid chromatography
Spectral condition is：Chromatographic column be Venusil XBP C18 (10 μm,50*250mm), mobile phase is first alcohol and water, mobile phase
Flow velocity is 80mLmin-1, gradient 0-30min：- 75% methanol of 50% methanol (v/v), Detection wavelength 254nm, sample size
1ml, operation temperature are 30 DEG C, collect the fraction of 19min or so；
(3) it collects：Fraction is received in the brown bottle of outer wall package masking foil of advance nitrogen filling, is first being protected from light shape
A small amount of acetonitrile is blown away with nitrogen under state, is then directly lyophilized in freeze dryer, dry 1-ethoxy-2-hydroxy-4-propenyl benzene is obtained.
The preparation of sample is completed in 30min, product purity reaches 99.40%.
Embodiment 5
A kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene, including following steps：
(1) preparation of test solution：1-ethoxy-2-hydroxy-4-propenyl benzene sample is weighed, methanol is dissolved in, through 0.45um filter membranes
Filtering, obtains test solution；
(2) prepared by liquid chromatogram：The 1-ethoxy-2-hydroxy-4-propenyl benzene of high-purity, wherein color are obtained using preparative liquid chromatography
Spectral condition is：Chromatographic column be Venusil XBP C18 (10 μm,50*250mm), mobile phase is first alcohol and water, mobile phase
Flow velocity is 90mLmin-1, gradient 0-30min：- 75% methanol of 50% methanol (v/v), Detection wavelength 254nm, sample size
0.5ml, operation temperature are 30 DEG C, collect the fraction of 19min or so；
(3) it collects：It is received in the brown bottle of outer wall package masking foil of advance nitrogen filling, is first used under the state that is protected from light
Nitrogen blows away a small amount of acetonitrile, is then directly lyophilized in freeze dryer, obtains dry 1-ethoxy-2-hydroxy-4-propenyl benzene.In 30min
The preparation of sample is completed, product purity reaches 99.36%.
Embodiment 6：
A kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene, including following steps：
(1) preparation of test solution：1-ethoxy-2-hydroxy-4-propenyl benzene sample is weighed, methanol is dissolved in, through 0.45um filter membranes
Filtering, obtains test solution；
(2) prepared by liquid chromatogram：The 1-ethoxy-2-hydroxy-4-propenyl benzene of high-purity, wherein color are obtained using preparative liquid chromatography
Spectral condition is：Chromatographic column be Venusil XBP C18 (10 μm,50*250mm), mobile phase is first alcohol and water, mobile phase
Flow velocity is 100mLmin-1, gradient 0-30min：- 75% methanol of 50% methanol (v/v), Detection wavelength 254nm, sample size
1.5ml, operation temperature are 30 DEG C, collect the fraction of 19min or so；
(3) it collects：Fraction is received in the brown bottle of outer wall package masking foil of advance nitrogen filling, is first being protected from light shape
A small amount of acetonitrile is blown away with nitrogen under state, is then directly lyophilized in freeze dryer, dry 1-ethoxy-2-hydroxy-4-propenyl benzene is obtained.
The preparation of sample is completed in 30min, product purity reaches 99.38%.
Embodiment 7：
The present embodiment is differed only in embodiment 2：Collect the fraction of 18min or so.Products obtained therefrom purity reaches
99.37%.
Embodiment 8：
The present embodiment is differed only in embodiment 3：Collect the fraction of 16.5min or so.Products obtained therefrom purity reaches
99.37%.
Embodiment 9：
The present embodiment is differed only in embodiment 4：Collect the fraction of 19.6min or so.Products obtained therefrom purity reaches
99.39%.
Embodiment 10：
The present embodiment is differed only in embodiment 5：Collect the fraction of 20.3min or so.Products obtained therefrom purity reaches
99.35%.
Embodiment 11：
The present embodiment is differed only in embodiment 6：Collect the fraction of 20.8min or so.Product purity reaches
99.37%.
Finally it should be noted that：The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention,
Although the present invention is described in detail referring to the foregoing embodiments, for those skilled in the art, still may be used
With technical scheme described in the above embodiments is modified or equivalent replacement of some of the technical features.
All within the spirits and principles of the present invention, any modification, equivalent replacement, improvement and so on should be included in the present invention's
Within protection domain.
Claims (4)
1. a kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene, it is characterised in that：Including following steps：
(1) preparation of test solution：The sample containing 1-ethoxy-2-hydroxy-4-propenyl benzene is taken, is dissolved in acetonitrile or methanol, through 0.22 μ
M or 0.45 μm of membrane filtration, obtains test solution；
(2) prepared by liquid chromatogram：Test solution obtained by step (1) is prepared through liquid chromatogram, wherein chromatographic condition
For：Type of elution is gradient elution, and the gradient of elution is：0-30min, -75% acetonitrile of 50% acetonitrile；Or the gradient of elution is：
0-30min, -75% methanol of 50% methanol, chromatographic column are Venusil XBP C18,10 μm of filler particle size, apertureChromatography
Column dimension 50*250mm, flow rate of mobile phase are 80~100mLmin-1, Detection wavelength 254nm, sample size 0.5-1.5ml,
Operation temperature is 30 DEG C, and the fraction for collecting 16.5-20.8min obtains 1-ethoxy-2-hydroxy-4-propenyl benzene.
2. preparation method according to claim 1, it is characterised in that：Sample size 1ml, flow velocity 80ml/min.
3. preparation method according to claim 1, it is characterised in that：Collect the fraction of 19min.
4. preparation method according to claim 1, it is characterised in that：The fraction of collection is received in the outer of advance nitrogen filling
Wall wraps up in the brown bottle of masking foil, first blows away a small amount of acetonitrile with nitrogen under the state that is protected from light, then directly freezes in freeze dryer
It is dry, obtain dry 1-ethoxy-2-hydroxy-4-propenyl benzene.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610173909.6A CN105699555B (en) | 2016-03-24 | 2016-03-24 | A kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610173909.6A CN105699555B (en) | 2016-03-24 | 2016-03-24 | A kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105699555A CN105699555A (en) | 2016-06-22 |
| CN105699555B true CN105699555B (en) | 2018-09-11 |
Family
ID=56232627
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610173909.6A Expired - Fee Related CN105699555B (en) | 2016-03-24 | 2016-03-24 | A kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105699555B (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2956120B1 (en) * | 2013-02-13 | 2020-04-15 | The Procter and Gamble Company | Anise flavored medication |
| EP3791862A1 (en) * | 2013-09-11 | 2021-03-17 | Eagle Biologics, Inc. | Liquid protein formulations containing viscosity-lowering agents |
-
2016
- 2016-03-24 CN CN201610173909.6A patent/CN105699555B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN105699555A (en) | 2016-06-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Meemken et al. | Platinum-catalyzed asymmetric hydrogenation: spectroscopic evidence for an OHO hydrogen-bond interaction between substrate and modifier | |
| CN107337586A (en) | A kind of method of extraction purification cannabidiol in fiber crops from the Chinese | |
| CN102348975B (en) | The quantivative approach of carotenoids | |
| CN103789094A (en) | Method for extracting agilawood essential oil from agilawood chips | |
| CN106645480B (en) | The determination method of anthocyanin substance in a kind of blueberry | |
| CN102965199A (en) | Tea leaf aroma extraction method and application | |
| CN105699555B (en) | A kind of method for preparing liquid chromatography of 1-ethoxy-2-hydroxy-4-propenyl benzene | |
| CN106977416B (en) | A kind of method of quick preparation high-purity hydroxyl-alpha-sanshool | |
| CN107121507B (en) | A kind of bamboo shoot shell polyphenol substance measuring method | |
| CN105018235A (en) | Method for rapid extracting of rose essential oil from fresh rose flower | |
| CN104817445B (en) | A kind of isolated and purified physcione and method of rheum emodin from Rhizoma Polygoni Cuspidati | |
| CN102095812B (en) | Method for detecting acrylonitrile in cosmetics by using gas chromatograph-mass spectrography | |
| CN104844550B (en) | A kind of method that osthole and imperatorin are isolated and purified from Fructus Cnidii | |
| CN109810789A (en) | A kind of extracting method of ginkgo essential oil | |
| CN107033017B (en) | A kind of method of quick preparation high-purity hydroxyl-γ-sanshool | |
| CN104016955A (en) | Method for extracting myricetin by hovenia dulcis thunb | |
| CN105503981B (en) | The method that violet cabbage anthocyanidin is extracted from violet cabbage | |
| CN103012346B (en) | Preparation method of pectolinarigenin monomer | |
| CN101936967B (en) | Method for rapidly sampling and identifying essential oil in chestnut flowers | |
| CN107064334B (en) | The method of quality control of anthracene shellfish element | |
| CN105646429B (en) | A kind of method for preparing high-purity catechin gallate CG | |
| CN104628501A (en) | Method for separating and preparing diaryl heptane compounds in walnut green seedcase | |
| Yazdani et al. | Supercritical CO2 extraction of essential oil from clove bud: Effect of operation conditions on the selective isolation of eugenol and eugenyl acetate | |
| CN108088922A (en) | Fragrance component database in essence rapid screening database and tealeaves in essence high flux examination detection method, tealeaves in tealeaves | |
| CN109810014A (en) | A kind of two caffeoyl spermidine class compound selective enrichment methods in fructus lycii |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180911 Termination date: 20190324 |