CN105111051A - Green solvent for alpha-asarin synthesis and application method thereof - Google Patents
Green solvent for alpha-asarin synthesis and application method thereof Download PDFInfo
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- CN105111051A CN105111051A CN201510559910.8A CN201510559910A CN105111051A CN 105111051 A CN105111051 A CN 105111051A CN 201510559910 A CN201510559910 A CN 201510559910A CN 105111051 A CN105111051 A CN 105111051A
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- C07C41/01—Preparation of ethers
- C07C41/32—Preparation of ethers by isomerisation
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Abstract
The invention discloses a green solvent for alpha-asarin synthesis which comprises at least one of dimethyl carbonate and pinane. The application method comprises the following steps: dissolving a raw material cis/trans-asarin mixture in at least one of the dimethyl carbonate and pinane used as the solvent, adding a supported Pd-base catalyst, heating under reflux, reacting until the balance state while stirring, filtering out the catalyst, distilling under reduced pressure to remove the solvent, adding petroleum ether into the residue for washing, and recrystallizing to obtain the pure trans-isomer alpha-asarin. The isomerized solvent for alpha-asarin synthesis is nontoxic and harmless, and enhances the quality of the alpha-asarin and the safety of the alpha-asarin as a medicine. The solvent has higher flash point, and thus, has higher fire resistance and explosion resistance in the operation location. The distillation recovery of the solvent is easy to implement, and has the advantages of low energy consumption, high safety and environment friendliness. The solvent has lower vaporization heat than the solvent benzene, dichlorotoluene or ethyl acetate in the existing preparation method. The distillation recovery of the solvent is easy to implement and low in energy consumption.
Description
Technical field
The invention belongs to technical field prepared by organic compound, relate to a kind of green solvent for alpha-ararin synthesis and using method thereof particularly.
Background knowledge
Alpha-ararin, have another name called α-trans-Isoasarone, English name α-asarone, asarin, asarumcamphor, chemistry (E)-2 by name, 4, 5-trimethoxy-1-propenylbenzene and trans-2, 4, 5-trimethoxy-1-propenylbenzene, the effective constituent in aroid Chinese medicine Rhizoma Acori Graminei volatile oil (AcorustatarinowiiSchottNaphtha), confirm there is very strong pharmacologically active, there is cough-relieving, remove phlegm, calm, relieving asthma, spasmolysis, anticonvulsion, antiulcer agent, anticancer, reducing blood-fat, the multiple pharmacologically active such as antiplatelet, simultaneously for streptococcus pneumoniae, streptococcus aureus and colibacillary growth have restraining effect in various degree, recent research finds that another outstanding drug effect of alpha-ararin is anti-epileptic grand mal, be widely used in the illness such as treatment upper respiratory tract infection, bronchitis, bronchial asthma, acute and chronic cholecystitis, cholelithiasis, epilepsy grand mal clinically, especially the treatment for the acute attack of pneumonia, bronchial asthma and chronic obstructive pulmonary disease has unusual effect, and can be used as the choice drug of the sick grand mal of the insane disease of control, it is also conventional medicine intermediate simultaneously.Although alpha-ararin can extract from the volatile oil of the plant such as Rhizome of Grass leaf Sweelflag, Rhizoma Acori Calami, but natural resources of Chinese medicinal materials is limited and its content in natural plant volatile oil is very low, complicated causes extracting sterling difficulty, very easily be mixed into the carcinogenss such as yellow Chinese catalpa ether simultaneously, and oneself confirmation of the alpha-ararin of synthetic does not contain yellow Chinese catalpa ether, toxicity is low, without additive; But be generally mixed with β-propenyl-2,4,5-trimethoxy beozene in the alpha-ararin of synthesis, this composition has been proved has Teratogenesis toxicity, and therefore how effectively propenyl-2,4,5-trimethoxy beozene cis-isomeride β-propenyl-2,4,5-trimethoxy beozene being converted into trans-isomer(ide) alpha-ararin becomes one of gordian technique that commercial synthesis alpha-ararin will solve.
Current domestic main synthetic method has: patent CN1511817A discloses a kind of process for producing alpha-asarone raw material, and it comprises the following production phase: be raw material with acetic anhydride, para benzoquinone etc., after acetylization reaction, methylation reaction, aldehyde glycosylation reaction, vinylation reaction and recrystallization, obtain alpha-ararin; The people such as Wang Zhicai, Jiang Lasheng, Xu Xingxiang are at " organic chemistry " (1990,10 (4): 350-352) propose in 2,4,5-trimethoxy formaldehyde is raw material, through two kinds of isomer of Griganard and Writtig Reactive Synthesis propenyl-2,4,5-trimethoxy beozene, underpressure distillation recrystallization also obtains alpha-ararin after chromatographic separation.Analogy like and, the people such as Feng Xunbo, Chen Chaoyue is in " synthetic chemistry " (2006,14 (5): 500-502) report with 2,4,5-TMB and ethyl phosphonium bromide reactive magnesium obtained 2,4,5. trimethoxyphenyl propyl alcohol (1), 1 has synthesized alpha-ararin through dehydration.The product that above preparation method obtains mostly be α-with two kinds of isomer mixtures of β-propenyl-2,4,5-trimethoxy beozene, must concentrate to be separated with chromatography etc. through underpressure distillation, recrystallization afterwards and just can obtain trans alpha-ararin.The public not a kind of preparation method of alpha-ararin of CN101012159, with suitable trans-propenyl-2,4,5-trimethoxy beozene for raw material, be dissolved in solvent, adding a certain amount of palladium compound is catalyzer, filter out catalyzer after reaction reaches balance, concentrating under reduced pressure reaction solution can obtain alpha-ararin, though this method overcome aforesaid method product be α-with the deficiency of β-propenyl-2,4,5-trimethoxy beozene mixture, by α-need for benzene, toluene dichloride etc. have highly toxic organic solvent with during the mixture of β-propenyl-2,4,5-trimethoxy beozene via palladium-catalyzed dose of isomerization reaction.CN200810030403.5 discloses a kind of method of synthesizing alpha-ararin, by suitable anti-α/β-propenyl-2,4,5-trimethoxy beozene mixture that the wittig in prior art is obtained by reacting, be dissolved in solvent with α/β-propenyl-2,4,5-trimethoxy beozene mixture for raw material again, under iodine catalyst effect, cis propenyl-2,4,5-trimethoxy beozene changed into trans propenyl-2,4,5-trimethoxy beozene.But the iodine catalyst of this method is volatile, distillation is not easily reclaimed, and the organic solvent ethyl acetate of use has certain toxicity, and its rat lethal quantity is 5620mg/kg; Be: have hormesis to eye, nose, throat that high density sucks can cause Progressive symmetric erythrokeratodermia anesthetic action, acute lung edema, liver, renal impairment to the harm of HUMAN HEALTH; Continue a large amount of suction, can cause respiratory paralysis, the person of wrongly taking can produce Nausea and vomiting, stomachache, diarrhoea etc.; There is sensitization, cause gingival hemorrhage because of nervus vasculairs obstacle; Eczema-like dermatitis can be caused; Long Term Contact benzene can cause the corneal opacity, secondary anemia, leukocytosis etc.
Benzene and toluene dichloride are highly toxic organic solvents, and wherein benzene is a kind of carcinogenic substance; The physical properties of benzene is boiling point is 80.1 DEG C, and fusing point is 5.5 DEG C, and flash-point is-11.1 DEG C, and vaporization heat is 394.8kJ/kg; The physical properties of toluene dichloride is boiling point is 197 DEG C, and fusing point is 2.6 DEG C, and flash-point is 86 DEG C, and vaporization heat is 342.5kJ/kg.Ethyl acetate has certain toxicity, and its physical properties fusing point is-83.6 DEG C, and boiling point is 77.06 DEG C, and flash-point is 7.2 DEG C, and vaporization heat is 404.6kJ/kg.Methylcarbonate solution (dimethylcarbonate, DMC) is a kind of solvent of environmental protection, is classified as nonpoisonous chemicla in 1992 by Europe, and rat lethal quantity is 13.8g/kg.The Main physical character fusing point of DMC is 3.0 DEG C, boiling point is 90.2 DEG C, flash-point is 22 DEG C, vaporization heat is 329.2kJ/kg, DMC is a kind of water white transparency at normal temperatures, there is the liquid of aromatic odour, there is the features such as nontoxic, non-corrosiveness, viscosity are low, surface tension is large and intermiscibility is good, and vaporization heat is low, relative evaporation speed is fast; Owing to containing methyl, carbonyl, methoxyl group and carbomethoxy in its molecule, organism that can be nearly all with alcohols and ethers etc. mixes.The rosin secreted by pine tree of pinane through fractionation by distillation natural essential oil (principal constituent firpene) hydrogenation and obtain, toxicity is low, security is good, pinane fusing point boiling point is 143 DEG C, flash-point is 39.9 DEG C, vaporization heat is 253.2kJ/kg, and pinane is natural product, has renewable and environmental protection dual nature advantage.
As can be seen here, existing by preparing benzene in the method for alpha-ararin, toluene dichloride hazardous and noxious substances along trans-propenyl-2,4,5-trimethoxy beozene mixture isomery, ethyl acetate also has certain toxicity, has larger injury to the person and environment.The vaporization heat of benzene, toluene dichloride, ethyl acetate, DMC and pinane is respectively 394.8kJ/kg, 342.5kJ/kg, 4014.6kJ/kg, 329.2 and 253.2kJ/kg, and therefore distillating recovering solvent DMC is more energy-conservation than benzene, toluene dichloride and ethyl acetate with pinane.In sum, because benzene, toluene dichloride and ethyl acetate have certain toxicity, and solvent inevitably residues in product, have impact on the safety of the alpha-ararin used as medicine.
For above-mentioned defect in alpha-ararin preparation process, the present invention proposes a kind of green solvent for alpha-ararin synthesis and using method thereof, with along trans-propenyl-2,4,5-trimethoxy beozene mixture be raw material, nontoxic methylcarbonate (dimethylcarbonate, DMC) and pinane green solvent be solubilising reagent, prepare high purity alpha-ararin through Pd base supported catalyst, and high-content trans pinane is conducive to the selectivity improving the synthesis of trans alpha-ararin.
Summary of the invention
The present invention is directed to the deficiency of existing technology of preparing, invent a kind of green solvent for alpha-ararin synthesis and using method thereof, making along trans-propenyl-2,4,5-trimethoxy beozene mixture is that raw material prepares that the process energy consumption of alpha-ararin is low, solvent recuperation is easy, environmental protection, simple to operate, safe and reliable, and high-content trans pinane is conducive to the selectivity improving the synthesis of trans alpha-ararin.
Main contents of the present invention are as follows:
For a green solvent for alpha-ararin synthesis, described solvent comprises following important component: at least one material in methylcarbonate, pinane.
Preferably, when methylcarbonate, both pinanes mix, be: methylcarbonate 50% ~ 100% that pinane is for being less than or equal to 50%, and in pinane solvent, the content of trans pinane is not less than 50%, be then conducive to the synthesis of trans alpha-ararin by mass percentage.
A kind of using method of the green solvent for the preparation of alpha-ararin: in preparation synthesis alpha-ararin process, to be dissolved at least one solvent in methylcarbonate, pinane along trans-propenyl-2,4,5-trimethoxy beozene mixture, input loading type Pd is catalyst based, be heated to backflow and react under whipped state to balancing stopped reaction, elimination catalyzer, underpressure distillation is except desolventizing, and residuum adds petroleum ether, can obtain pure trans-isomer(ide) alpha-ararin after recrystallization.
Preferred raw material: solvent (w: w)=1: 5 ~ 1: 10.
In preferred pinane solvent, the content of trans pinane is not less than 50%.
The catalyst based input amount of preferred loading type Pd is 1 ~ 5% of raw materials quality.
Preferred temperature of reaction is the boiling temperature of reaction mixture.
The preferred reaction times is 7 ~ 10 hours.
Beneficial effect of the present invention:
The present invention uses at least one in methylcarbonate, pinane as the solvent of preparation synthesis alpha-ararin, nontoxic, the quality that improve alpha-ararin and the security used as medicine thereof; The flash-point of further solvent for use methylcarbonate and pinane is higher, and in operationlocation, fire-proof and explosion-proof performance is better; And the vaporization heat of DMC and pinane is respectively 329.2 and 253.2kJ/kg in solvent for use, be less than the vaporization heat (394.8kJ/kg, 342.5kJ/kg and 4014.6kJ/kg) of existing preparation method's solvent for use benzene, toluene dichloride and ethyl acetate, easily realize when distillating recovering solvent, power consumption is few, safety and environmental protection; And high-content trans pinane is conducive to the selectivity improving the synthesis of trans alpha-ararin.
Embodiment
Further describe the present invention referring to embodiment, to make those skilled in the art can implement according to this with reference to specification sheets word, scope is not limited by embodiments of the present invention.Raw material used in embodiment reacts the suitable anti-α/β-propenyl-2,4,5-trimethoxy beozene mixture obtained for wittig.
Embodiment 1
Take methylcarbonate 25g, pinane 25g (wherein trans pinane 23g cis-pinane 2 grams), be hybridly prepared into the solvent of isomerization reaction, take raw material along anti-α/β-propenyl-2,4,5-trimethoxy beozene mixture 10g is dissolved in solvent, adds Supported Pd-Catalyst 0.1g, then drop into together and be equipped with in the there-necked flask of mechanical stirrer, thermometer and reflux condensing tube, be placed in a bowl formula electric mantle and be warming up to solvent boiling point, return stirring 7 hours, isomerization reaction reaches balance, stopped reaction.Solvent is removed in first air distillation again underpressure distillation, adds 35ml sherwood oil, stirs 10min, filters, and decompression extracts sherwood oil, obtains 41.1g oily matter, and to be 82.1%, GC detected result be yield that alpha-ararin accounts for 98.5%, β-propenyl-2,4,5-trimethoxy beozene accounts for 1.5%.Oily matter obtains white alpha-ararin crystal 6.1g after normal hexane recrystallization.
Embodiment 2
Take the solvent of methylcarbonate 200g as isomerization reaction, take raw material along anti-α/β-propenyl-2,4,5-trimethoxy beozene mixture 20g is dissolved in solvent, add Supported Pd-Catalyst 1g, then dropping into together is equipped with in the there-necked flask of mechanical stirrer, thermometer and reflux condensing tube, be placed in a bowl formula electric mantle and be warming up to solvent boiling point, return stirring 10 hours, isomerization reaction reaches balance, stopped reaction.Solvent is removed in first air distillation again underpressure distillation, adds 65ml sherwood oil, stirs 15min, filters, and decompression extracts sherwood oil, obtains 17.04g oily matter, and to be 85.2%, GC detected result be yield that alpha-ararin accounts for 97.9%, β-propenyl-2,4,5-trimethoxy beozene accounts for 2.1%.Oily matter obtains white alpha-ararin crystal 15.9g after normal hexane recrystallization.
Embodiment 3
Take methylcarbonate 56g, pinane 14g (wherein trans pinane 11g cis-pinane 3 grams) is hybridly prepared into the solvent of isomerization reaction, take raw material along anti-α/β-propenyl-2,4,5-trimethoxy beozene mixture 6g is dissolved in solvent, add Supported Pd-Catalyst 0.18g, then drop into together and be equipped with in the there-necked flask of mechanical stirrer, thermometer and reflux condensing tube, be placed in a bowl formula electric mantle and be warming up to solvent boiling point, return stirring 6 hours, isomerization reaction reaches balance, stopped reaction.Solvent is removed in first air distillation again underpressure distillation, adds 20ml sherwood oil, stirs 10min, filters, and decompression extracts sherwood oil, obtains 5.1g oily matter, and to be 84.7%, GC detected result be yield that alpha-ararin accounts for 98.7%, β-propenyl-2,4,5-trimethoxy beozene accounts for 1.3%.Oily matter obtains white alpha-ararin crystal 4.9g after normal hexane recrystallization.
Embodiment 4
Take methylcarbonate 77g, pinane 19g (wherein trans pinane 13g cis-pinane 6 grams) is hybridly prepared into the solvent of isomerization reaction, take raw material along anti-α/β-propenyl-2,4,5-trimethoxy beozene mixture 12g is dissolved in solvent, add Supported Pd-Catalyst 0.36g, then drop into together and be equipped with in the there-necked flask of mechanical stirrer, thermometer and reflux condensing tube, be placed in a bowl formula electric mantle and be warming up to solvent boiling point, return stirring 8 hours, isomerization reaction reaches balance, stopped reaction.Solvent is removed in underpressure distillation, adds 40ml sherwood oil, stirs 12min, filters, and decompression extracts sherwood oil, obtains 10.6g oily matter, and to be 88.3%, GC detected result be yield that alpha-ararin accounts for 98.2%, β-propenyl-2,4,5-trimethoxy beozene accounts for 1.8%.Oily matter obtains white alpha-ararin crystal 9.9g after normal hexane recrystallization.
Embodiment 5
Take methylcarbonate 144g, pinane 36g (wherein trans pinane 22g cis-pinane 14 grams) is hybridly prepared into the solvent of isomerization reaction, take raw material along anti-α/β-propenyl-2,4,5-trimethoxy beozene mixture 30g is dissolved in solvent, add Supported Pd-Catalyst 1.2g, then drop into together and be equipped with in the there-necked flask of mechanical stirrer, thermometer and reflux condensing tube, be placed in a bowl formula electric mantle and be warming up to solvent boiling point, return stirring 9 hours, isomerization reaction reaches balance, stopped reaction.Solvent is removed in first air distillation again underpressure distillation, adds 90ml sherwood oil, stirs 20min, filters, and decompression extracts sherwood oil, obtains 26.1g oily matter, and to be 86.9%, GC detected result be yield that alpha-ararin accounts for 98.1%, β-propenyl-2,4,5-trimethoxy beozene accounts for 1.9%.Oily matter obtains white alpha-ararin crystal 24.7g after normal hexane recrystallization.
Claims (4)
1., for a solvent for the green solvent of alpha-ararin synthesis, it is characterized in that, comprise following component: methylcarbonate, pinane or the mixing solutions of the two.
2., according to claim 1 for the solvent of alpha-ararin, it is characterized in that: its by mass percentage, methylcarbonate is 50% ~ 100%, and pinane is for being less than or equal to 50% ~ 100%.
3. using method according to claim 2, is characterized in that: in pinane solvent, the content of trans pinane is not less than 50%, and high-content trans pinane is conducive to the selectivity improving the synthesis of trans alpha-ararin.
4. using method according to claim 1, it is characterized in that: raw material is dissolved at least one solvent in methylcarbonate, pinane along trans-propenyl-2,4,5-trimethoxy beozene mixture, input loading type Pd is catalyst based, be heated to backflow and react under whipped state to balancing stopped reaction, consider or suction filtration removing catalyzer through pressure, after first normal pressure, underpressure distillation is except desolventizing, and residuum adds petroleum ether, can obtain pure trans-isomer(ide) alpha-ararin after recrystallization.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110156574A (en) * | 2019-07-03 | 2019-08-23 | 承德石油高等专科学校 | A kind of preparation method of purification of alpha-ararin |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101012159A (en) * | 2006-03-15 | 2007-08-08 | 浙江大学宁波理工学院 | Method of preparing alpha-asarone |
| CN101215226A (en) * | 2008-01-02 | 2008-07-09 | 湖南师范大学 | Method for synthesizing alpha-asarone |
| CN103571537A (en) * | 2013-11-19 | 2014-02-12 | 广西大学 | Dewaxing solvent and use method thereof |
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2015
- 2015-09-07 CN CN201510559910.8A patent/CN105111051A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101012159A (en) * | 2006-03-15 | 2007-08-08 | 浙江大学宁波理工学院 | Method of preparing alpha-asarone |
| CN101215226A (en) * | 2008-01-02 | 2008-07-09 | 湖南师范大学 | Method for synthesizing alpha-asarone |
| CN103571537A (en) * | 2013-11-19 | 2014-02-12 | 广西大学 | Dewaxing solvent and use method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110156574A (en) * | 2019-07-03 | 2019-08-23 | 承德石油高等专科学校 | A kind of preparation method of purification of alpha-ararin |
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