CN108558983A - A kind of method that separation prepares four kinds of active materials of cycloartenyl ferulate - Google Patents
A kind of method that separation prepares four kinds of active materials of cycloartenyl ferulate Download PDFInfo
- Publication number
- CN108558983A CN108558983A CN201810457888.XA CN201810457888A CN108558983A CN 108558983 A CN108558983 A CN 108558983A CN 201810457888 A CN201810457888 A CN 201810457888A CN 108558983 A CN108558983 A CN 108558983A
- Authority
- CN
- China
- Prior art keywords
- acid ester
- ferulic acid
- cycloartenyl
- purity
- cycloartenyl ferulate
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
- C07J53/002—Carbocyclic rings fused
- C07J53/004—3 membered carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Abstract
The present invention relates to a kind of methods for being detached from rice rice bran extract with counter current chromatography and preparing high-purity monomer cycloartenyl ferulate, 24 methylene cycloartenyl ferulates, campesterol ferulic acid ester and sitosterol ferulic acid ester；It is to detach four kinds of active materials, the dicyandiamide solutions such as preparation high-purity cycloartenyl ferulate from rice rice bran extract using counter current chromatography to be made of three components：Petroleum ether or n-alkane, dichloromethane and acetonitrile or fatty alcohol；Volume ratio is：10：0‑3：7‑12；Suitable for preparing monomer cycloartenyl ferulate, 24 methylene cycloartenyl ferulates, campesterol ferulic acid ester and sitosterol ferulic acid ester using various model counter-current chromatograph separation, it can be directly into a large amount of crude products or synthetic mixture, cycloartenyl ferulate and sitosterol ferulic acid ester purity are detached up to 95% or more, 24 methylene cycloartenyl ferulate and campesterol ferulic acid ester purity up to 90% or more.
Description
Technical field
High-purity monomer is prepared using high-speed countercurrent chromatography separation from rice rice bran extract the present invention relates to a kind of
Cycloartenyl ferulate, 24- methylene cycloartenyl ferulate, campesterol ferulic acid ester and sitosterol Ah
The preparative separation method of Wei's acid esters.
Background technology
Rice is second-biggest-in-the-world crops, about 5.83 hundred million tons of annual output, and China is maximum rice production state in the world,
Annual to generate 2.0 hundred million tons of paddy or more, rice bran annual output is up to 14,000,000 tons or so.Rice bran is the valuable by-product of rice processing industry
One of product have proven to be dispersed with a large amount of sterol ferulates in the cereal processing waste such as rice rice bran（About 2510-6860
μg/g）Deng having effects that the component of bioactivity, predominantly ring jackfruit alcohols ferulic acid ester and campesterol ferulic acid ester,
Middle cycloartenyl ferulate accounts for 32%, 24- methylene cycloartenyl ferulates and accounts for 40%, campesterol ferulic acid
Ester accounts for 9%, and sitosterol ferulic acid ester accounts for 19%.Sterol ferulate is that the hydroxyl on the positions sterol C3 is combined with ferulic acid, is dehydrated shape
At a kind of derivative, there is preferable lipophilicity, be more easy to penetrate biomembrane, thus specific ionization sterol and ferulic acid have it is more aobvious
The lipid-loweringing of work is horizontal, anti-oxidant, anti-inflammatory, antiviral and antitumor etc. comprehensive organisms effect.Therefore, it isolates and purifies in rice rice bran
The substances such as cycloartenyl ferulate are of great significance for the utilization of agricultural and sideline product high added value.
Existing literature report uses column chromatography isolated sterol ferulate from rice rice bran, but can not obtain
The monomer of extreme high purity is obtained, and adverse current chromatogram method for separating and preparing can obtain high-purity monomer.Due to high speed adverse current chromatogram
(High-speed Countercurrent Chromatography, HSCCC) is that one kind for growing up in recent years is continuous
Without efficient, the quick liquid liquid partition chromatography isolation technics of any solid support, it avoids solid state adhesion body or carrier
For the various problem-samples brought easily by absorption, loss and denaturation, HSCCC ensures higher peak type resolution, and fractional dose is big, sample
Free of losses, rate of recovery height, isolating environment mitigate, and save solvent.Counter-current chromatograph can directly into largely slightly get sample product or synthesis it is mixed
Object is closed, separating resulting can reach quite high purity, or even can directly be connect with instruments such as mass spectrographs, be widely used to give birth to
The preparative separation of the fields such as object, medicine, environmental protection chemical substance and purifying.And cycloartenyl ferulate, 24- methylene basic rings
Four kinds of jackfruit enol ferulic acid ester, campesterol ferulic acid ester and sitosterol ferulic acid ester substances are non-polar compound, object
Matter structure is very much like, it is difficult to isolate and purify acquisition high-purity monomer.
Invention content
The purpose of the present invention is the rice rice bran extract extracted using n-hexane is raw material by the lower ring jackfruit of content
Enol ferulic acid ester, 24- methylene cycloartenyl ferulate, campesterol ferulic acid ester and sitosterol ferulic acid ester warp
The method of high speed adverse current chromatogram obtains the cycloartenyl ferulate and sitosterol ferulic acid ester of 95% or more purity, obtains
90% or more 24- methylene cycloartenyl ferulate of purity and campesterol ferulic acid ester.
The scheme of the invention is：Rice rice bran extract is detached by counter current chromatography and prepares high-purity cycloartenol
Ferulic acid ester, 24- methylene cycloartenyl ferulate, campesterol ferulic acid ester and sitosterol ferulic acid ester.Selection
Two-phase non-aqueous solvent system is made of three components, and component A is petroleum ether, n-alkane, and B component is dichloromethane, component C
It is acetonitrile, fatty alcohol.
Using non-aqueous solvent system, the above phase is stationary phase, and lower phase is mobile phase, is ensureing that phase volume ratio is less than 1 up and down
Under the premise of, A is adjusted in the case where not destroying system balance according to solubility constant:B:The volume ratio of tri- components of C:10:0-
3：7-12 obtains cycloartenyl ferulate, 24- methylene cycloartenol ferulic acids by a counter-current separation
Ester, campesterol ferulic acid ester and sitosterol ferulic acid ester.
Experiment condition is suitble to 10-25 DEG C of room temperature, and room temperature is affected to separative efficiency, and optimal separation temperature is 15 DEG C, such as
Fruit temperature is excessive, and dicyandiamide solution reservation is very poor, is unable to reach separation requirement.
Above-mentioned dicyandiamide solution is formulated in separatory funnel by volume first, shakes up rear stratification.One section of ready to balance
After time, upper and lower phase is separated.Using analytic type or semi-preparative high-speed counter-current chromatograph, pumped equipped with NS-1007,2mL
Or 20mL sampling valves, polytetrafluoroethylene (PTFE) column, column volume 40mL, 230 or 240mL, 500mL, 8823A-UV UV detector,
3057 Portable type recorders of Yokogawa.Rice rice bran extract is dissolved in mobile phase for use.Before sample introduction, first with fixation
It is mutually filled with entire pillar, adjustment engine speed is 500-1800 rpm, and mobile phase is pumped into column with the flow velocity of 0.5-3.0mL/min
It is interior, after whole system establishes dynamic equilibrium, by sample introduction valve injection；Then according to detector uv atlas, target component is received.
The cycloartenyl ferulate and sitosterol ferulic acid ester its purity extracted with this method can reach 95% with
On, 24- methylene cycloartenyl ferulate and campesterol ferulic acid ester purity reach 90% or more.Suitable for using
The counter-current chromatograph separation of various models prepares cycloartenyl ferulate, 24- methylene cycloartenol ferulic acids
Ester, campesterol ferulic acid ester and sitosterol ferulic acid ester monomer, can be directly into product or the synthetic mixture of largely slightly getting sample, separation
As a result it can reach high purity.
Specific implementation mode
Embodiment 1
It chooses n-hexane-acetonitrile and isolates and purifies rice rice bran extract on semi-preparative counter-current chromatograph GS10AB, first
Above-mentioned solvent composition is formulated in separatory funnel by 1 ︰, 1 volume ratios, shakes up rear stratification.Ready to balance for a period of time after, will
Upper and lower phase separates, and removes and is mutually used as stationary phase, upper phase is as mobile phase.Using semi-preparative high-speed counter-current chromatograph, match
There are NS-1007 pumps, 20mL sampling valves, polytetrafluoroethylene (PTFE) column, column volume 240mL, 8823A-UV UV detector, Yokogawa
3057 Portable type recorders.Weigh 200mg rice rice bran extracts be dissolved on 5mL mutually with mixed under 5mL it is for use in solution.
Before sample introduction, first entire pillar is filled with stationary phase, adjustment engine speed is 800rpm, with the flow velocity of 1.5mL/min by mobile phase
It is pumped into column；After whole system establishes dynamic equilibrium, by sample introduction valve injection；Then according to detector uv atlas, mesh is received
Ingredient is marked, HPLC detection cycloartenyl ferulates and sitosterol ferulic acid ester purity reach 95% or more, 24- methylene
The purity of cycloartenyl ferulate and campesterol ferulic acid ester reaches 90% or more.
Embodiment 2
It chooses normal heptane-dichloromethane-acetonitrile and detaches rice rice bran extract on semi-preparative counter-current chromatograph GS10A,
10 ︰ 2 are pressed first：Above-mentioned solvent composition is formulated in separatory funnel by 8 volume ratios, shakes up rear stratification.When one section of ready to balance
Between after, upper and lower phase is separated, remove mutually be used as stationary phase, upper phase is as mobile phase.Using semi-preparative high-speed counter-current color
Spectrometer pumps, 20mL sampling valves, polytetrafluoroethylene (PTFE) column, column volume 230mL, 8823A-UV UV detector equipped with NS-1007,
3057 Portable type recorders of Yokogawa.Weigh 128.5mg rice rice bran extracts be dissolved on 5mL mutually with mixed under 5mL
It is for use in solution.Before sample introduction, it first is filled with entire pillar with stationary phase, adjustment engine speed is 800rpm, with the stream of 2.0mL/min
Mobile phase is pumped into column by speed；After whole system establishes dynamic equilibrium, by sample introduction valve injection；Then according to detector UV spectrum
Figure receives target component, and HPLC detection cycloartenyl ferulates and sitosterol ferulic acid ester purity reach 95% or more,
The purity of 24- methylene cycloartenyl ferulate and campesterol ferulic acid ester reaches 90% or more.
Embodiment 3
Selection pentane-dichloromethane-acetonitrile isolates and purifies rice rice bran on semi-preparative counter-current chromatograph EMC-500 and carries
Object is taken, presses 10 ︰ 3 first：Above-mentioned solvent composition is formulated in separatory funnel by 7 volume ratios, shakes up rear stratification.Ready to balance one
After the section time, upper and lower phase is separated, removes and is mutually used as stationary phase, upper phase is as mobile phase.It is inverse using semi-preparative high speed
Flow chromatography instrument pumps, 20mL sampling valves, polytetrafluoroethylene (PTFE) column, column volume 500mL, 8823A-UV ultraviolet detection equipped with NS-1007
Device, 3057 Portable type recorders of Yokogawa.It weighs 400.2mg rice rice bran extracts and is dissolved in phase and phase under 5mL on 5mL
It is for use in mixed solution.Before sample introduction, it first is filled with entire pillar with stationary phase, adjustment engine speed is 800rpm, with 2.0mL/min
Flow velocity mobile phase is pumped into column；After whole system establishes dynamic equilibrium, by sample introduction valve injection；Then according to detector purple
Outer spectrogram, receive target component, HPLC detection cycloartenyl ferulate and sitosterol ferulic acid ester purity reach 95% with
On, the purity of 24- methylene cycloartenyl ferulate and campesterol ferulic acid ester reaches 90% or more.
Embodiment 4
It chooses n-hexane-ethyl alcohol and isolates and purifies rice rice bran extract on semi-preparative counter-current chromatograph GS10AB, first
By 5：Above-mentioned solvent composition is formulated in separatory funnel by 6 volume ratios, shakes up rear stratification.Ready to balance for a period of time after, will
Upper and lower phase separates, and removes and is mutually used as stationary phase, upper phase is as mobile phase.Using semi-preparative high-speed counter-current chromatograph, match
There are NS-1007 pumps, 20mL sampling valves, polytetrafluoroethylene (PTFE) column, column volume 240mL, 8823A-UV UV detector, Yokogawa
3057 Portable type recorders.It weighs 133.6mg rice rice bran extracts and is dissolved on 5mL and mutually wait for being mixed in solution under 5mL
With.Before sample introduction, it first is filled with entire pillar with stationary phase, adjustment engine speed is 800rpm, will be flowed with the flow velocity of 2.0mL/min
Mutually it is pumped into column；After whole system establishes dynamic equilibrium, by sample introduction valve injection；Then it according to detector uv atlas, receives
Target component, HPLC detection cycloartenyl ferulates and sitosterol ferulic acid ester purity reach 95% or more, 24- methylenes
The purity of base cycloartenyl ferulate and campesterol ferulic acid ester reaches 90% or more.
Embodiment 5
It chooses n-hexane-methanol and isolates and purifies rice rice bran extract on semi-preparative counter-current chromatograph GS10AB, first
By 1:Above-mentioned solvent composition is formulated in separatory funnel by 1 volume ratio, shakes up rear stratification.Ready to balance for a period of time after, will
Upper and lower phase separates, and removes and is mutually used as stationary phase, upper phase is as mobile phase.Using semi-preparative high-speed counter-current chromatograph, match
There are NS-1007 pumps, 20mL sampling valves, polytetrafluoroethylene (PTFE) column, column volume 240mL, 8823A-UV UV detector, Yokogawa
3057 Portable type recorders.It weighs 299.3mg rice rice bran extracts and is dissolved on 5mL and mutually wait for being mixed in solution under 5mL
With.Before sample introduction, it first is filled with entire pillar with stationary phase, adjustment engine speed is 800rpm, will be flowed with the flow velocity of 2.0mL/min
Mutually it is pumped into column；After whole system establishes dynamic equilibrium, by sample introduction valve injection；Then it according to detector uv atlas, receives
Target component, HPLC detection cycloartenyl ferulates and sitosterol ferulic acid ester purity reach 95% or more, 24- methylenes
The purity of base cycloartenyl ferulate and campesterol ferulic acid ester reaches 90% or more.
Embodiment 6
It chooses petroleum ether-n-butanol and isolates and purifies rice rice bran extract on semi-preparative counter-current chromatograph GS10AB, it is first
First press 1:Above-mentioned solvent composition is formulated in separatory funnel by 1 volume ratio, shakes up rear stratification.Ready to balance for a period of time after,
Upper and lower phase is separated, removes and is mutually used as stationary phase, upper phase is as mobile phase.Using semi-preparative high-speed counter-current chromatograph,
It is pumped equipped with NS-1007,20mL sampling valves, polytetrafluoroethylene (PTFE) column, column volume 240mL, 8823A-UV UV detector,
3057 Portable type recorders of Yokogawa.Weigh 150.1mg rice rice bran extracts be dissolved on 5mL mutually with mixed under 5mL
It is for use in solution.Before sample introduction, it first is filled with entire pillar with stationary phase, adjustment engine speed is 800rpm, with the stream of 3.0mL/min
Mobile phase is pumped into column by speed；After whole system establishes dynamic equilibrium, by sample introduction valve injection；Then according to detector UV spectrum
Figure receives target component, and HPLC detection cycloartenyl ferulates and sitosterol ferulic acid ester purity reach 95% or more,
The purity of 24- methylene cycloartenyl ferulate and campesterol ferulic acid ester reaches 90% or more.
Embodiment 7
It chooses methyl tertiary butyl ether(MTBE)-n-butanol and isolates and purifies rice rice bran extract on analytic type counter-current chromatograph GS20,
1 is pressed first:Above-mentioned solvent composition is formulated in separatory funnel by 1 volume ratio, shakes up rear stratification.Ready to balance is for a period of time
Afterwards, upper and lower phase is separated, removes and be mutually used as stationary phase, upper phase is as mobile phase.Using analytic type counter-current chromatograph, it is furnished with
NS-1007 is pumped, 2mL sampling valves, polytetrafluoroethylene (PTFE) column, column volume 40mL, 8823A-UV UV detector, Yokogawa
3057 Portable type recorders.It weighs 30.5mg rice rice bran extracts and is dissolved on 1mL and mutually wait for being mixed in solution under 1mL
With.Before sample introduction, it first is filled with entire pillar with stationary phase, adjustment engine speed is 1800rpm, will be flowed with the flow velocity of 0.5mL/min
Dynamic phase is pumped into column；After whole system establishes dynamic equilibrium, by sample introduction valve injection；Then it according to detector uv atlas, connects
Target component is received, HPLC detection cycloartenyl ferulates and sitosterol ferulic acid ester purity reach the Asias 95% or more, 24-
The purity of methyl cycloartenyl ferulate and campesterol ferulic acid ester reaches 90% or more.
Claims (1)
1. a kind of method that separation prepares four kinds of active materials of cycloartenyl ferulate, it is characterised in that：It is to use
Counter current chromatography separation from rice rice bran extract prepares cycloartenyl ferulate, 24- methylene basic ring jackfruit alkene
Alcohol ferulic acid ester, campesterol ferulic acid ester and sitosterol ferulic acid ester, wherein cycloartenyl ferulate and sitosterol
Ferulic acid ester purity is 95% or more, 24- methylene cycloartenyl ferulate and campesterol ferulic acid ester purity is
90% or more, dicyandiamide solution is made of three components：By petroleum ether or n-hexane or normal heptane or pentane, dichloromethane and
Acetonitrile or methanol or ethyl alcohol or n-butanol are constituted, and volume ratio is followed successively by： 10：0-3：7-12.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810457888.XA CN108558983A (en) | 2018-05-14 | 2018-05-14 | A kind of method that separation prepares four kinds of active materials of cycloartenyl ferulate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810457888.XA CN108558983A (en) | 2018-05-14 | 2018-05-14 | A kind of method that separation prepares four kinds of active materials of cycloartenyl ferulate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108558983A true CN108558983A (en) | 2018-09-21 |
Family
ID=63538562
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810457888.XA Pending CN108558983A (en) | 2018-05-14 | 2018-05-14 | A kind of method that separation prepares four kinds of active materials of cycloartenyl ferulate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108558983A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111004302A (en) * | 2019-12-06 | 2020-04-14 | 湖南华诚生物资源股份有限公司 | A method for preparing 5 ferulic acid esters with soapstock containing oryzanol as raw material |
| CN111620775A (en) * | 2020-06-04 | 2020-09-04 | 浙江得乐康食品股份有限公司 | Method for preparing cycloartenyl ferulate by selectively hydrolyzing oryzanol |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102167693A (en) * | 2011-02-28 | 2011-08-31 | 北京化工大学 | Method for separating and preparing alpha-terthienyl, thianthrene and p-terphenyl |
-
2018
- 2018-05-14 CN CN201810457888.XA patent/CN108558983A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102167693A (en) * | 2011-02-28 | 2011-08-31 | 北京化工大学 | Method for separating and preparing alpha-terthienyl, thianthrene and p-terphenyl |
Non-Patent Citations (1)
| Title |
|---|
| 穆光照主编: "第三章溶剂的应用 三、溶剂的互溶性", 《实用溶剂手册》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111004302A (en) * | 2019-12-06 | 2020-04-14 | 湖南华诚生物资源股份有限公司 | A method for preparing 5 ferulic acid esters with soapstock containing oryzanol as raw material |
| CN111004302B (en) * | 2019-12-06 | 2021-03-19 | 湖南华诚生物资源股份有限公司 | A method for preparing 5 ferulic acid esters with soapstock containing oryzanol as raw material |
| CN111620775A (en) * | 2020-06-04 | 2020-09-04 | 浙江得乐康食品股份有限公司 | Method for preparing cycloartenyl ferulate by selectively hydrolyzing oryzanol |
| CN111620775B (en) * | 2020-06-04 | 2023-01-10 | 浙江得乐康食品股份有限公司 | Method for preparing cycloartenyl ferulate by selectively hydrolyzing oryzanol |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102976909B (en) | Method for extracting and purifying 6-gingerol from ginger | |
| US10954208B2 (en) | Method for synthesis of cannabis products | |
| CN106866602A (en) | A kind of method that application high speed adverse current chromatogram separates flavone compound in Hericium erinaceus | |
| CN105131077A (en) | Method for extracting peroxyergosterol from wall-broken ganoderma lucidum spore powder | |
| CN108558983A (en) | A kind of method that separation prepares four kinds of active materials of cycloartenyl ferulate | |
| Hwang et al. | Isolation of fucosterol from Pelvetia siliquosa by high-speed countercurrent chromatography | |
| CN102010387B (en) | Method for purifying orlistat | |
| CN106226426B (en) | A kind of method that high performance liquid chromatography splits canagliflozin five-membered ring impurity enantiomer | |
| CN105111061B (en) | A kind of preparation method of active compound for anti tumor | |
| CN101565437B (en) | Separation and preparation method of patuletin-3-O-glucoside and astragalin | |
| CN100427501C (en) | Method for separating and preparing ursolic acid and its derivative from persimmon leaf using counter current chromatography | |
| CN105541687A (en) | Method for synchronously separating and purifying beta-cryptoflavin and stigmasterol in orange peel | |
| CN108373474B (en) | A bilobalide compound extracted from folium Ginkgo and its preparation method | |
| CN100422188C (en) | Method for separating preparing tripterygium wilfordii monomer from tripterygium wilfordii by countercurrent flow chromatography | |
| CN106995361B (en) | A method of the separating beta-elemene from oil of zedoary turmeric | |
| CN101805352A (en) | Method for preparing eriocalyxin B | |
| CN102167693B (en) | Method for separating and preparing alpha-terthienyl, thianthrene and p-terphenyl | |
| CN105669604B (en) | A method of wildness hazel-mushroom taxol is purified using ultra high pressure extraction, biological enzymolysis, adverse current chromatogram | |
| CN1176904C (en) | Molecular distilling process for enriching and purifying capsaicin | |
| CN108409817A (en) | A method of preparing Quercetin -3-D- xylosides and Quercetin -3-D- Arabinosides | |
| Li et al. | Recovery of ganoderic acids from Ganoderma lucidum mycelia by macroporous adsorption resins | |
| CN109498686B (en) | Preparation method of triterpenic acid in jujube material | |
| CN104892383B (en) | Method for preparing p-hydroxybenzaldehyde from brined radish | |
| CN105985351B (en) | The preparation method of high purity sesamin monomer and sesamolin monomer | |
| CN104292091B (en) | A kind of extracting method of Capsorubin |
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 |
Application publication date: 20180921 |
|
| WD01 | Invention patent application deemed withdrawn after publication |