CN107827895A - A kind of method for the sildenafil citrate compound for preparing treatment male erectile dysfunction - Google Patents
A kind of method for the sildenafil citrate compound for preparing treatment male erectile dysfunction Download PDFInfo
- Publication number
- CN107827895A CN107827895A CN201711375487.1A CN201711375487A CN107827895A CN 107827895 A CN107827895 A CN 107827895A CN 201711375487 A CN201711375487 A CN 201711375487A CN 107827895 A CN107827895 A CN 107827895A
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- CN
- China
- Prior art keywords
- sildenafil citrate
- ethanol
- methylpyrrolidone
- dichloromethane
- mixed solvent
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The invention discloses a kind of method for the sildenafil citrate compound for preparing treatment male erectile dysfunction, belong to pharmaceutical technology field.The X ray powder diffraction patterns that sildenafil citrate compound prepared by the present invention is obtained using Cu K alpha ray measurements are as shown in Figure 1, test result indicates that, sildenafil citrate compound provided by the invention is not easy moisture absorption, moisture and impurity content is low, stability is good.
Description
The application is entitled：A kind of sildenafil citrate compound for treating male erectile dysfunction, Shen
Please number for 2015104363992 application for a patent for invention divisional application.
Technical field
The invention belongs to pharmaceutical technology field, is related to a kind of sildenafil citrate for treating male erectile dysfunction
Compound.
Background technology
Silaenafil is a kind of medicine for effectively treating Erectile Dysfunction illness caused by objective and subjective reason,
In March, 1997 lists through FDA approvals as prescription medicine in the U.S., and silaenafil is high selectivity PDE5 (PDE5)
Inhibitor, PDE5 altimeters in corpora cavernosa penis reach, and in other tissues（Including blood platelet, blood vessel and visceral smooth muscle,
Skeletal muscle）Expression is low.Silaenafil strengthens nitric oxide (NO)-cGMP approach, raises cGMP by selective depression PDE5
It is horizontal and cause corpus cavernosum smooth muscle to relax, patients with erectile dysfunction is produced natural erectile response to sexual stimulus.
Erectile response typically strengthens with the increase of silaenafil dosage and plasma concentration.
Sildenafil citrate hygroscopicity is strong, easy moisture absorption under normality and go bad, therefore the height of water content is to the steady of medicine
Qualitative effect is larger, it is necessary to strictly control product quality, and the preparation to preparation brings larger difficulty.Therefore, it is necessary to provide
A kind of sildenafil citrate compound of performance improvement.
The present inventor starts with from the research of sildenafil citrate solid chemical material existence, is made by substantial amounts of experiment
For a kind of sildenafil citrate crystalline compounds have been gone out, surprisingly found through overtesting, the compound crystal significantly improves
Its hygroscopicity, moisture and impurity content are low, substantially increase its stability.
The content of the invention
It is an object of the invention to propose a kind of sildenafil citrate compound for treating male erectile dysfunction.
In order to realize the purpose of the present invention, the technical scheme that uses for：
A kind of sildenafil citrate compound for treating male erectile dysfunction, it is characterised in that described citric acid west
The X-ray powder diffraction figure that non-compound of ground is obtained using Cu-K alpha ray measurements is as shown in Figure 1.
Polymorph in pharmaceuticals phenomenon is common problem in present drug research.The polymorphism of medicine can influence it
Physicochemical property, and then the clinical efficacy of medicine may be had influence on.Sildenafil citrate hygroscopicity of the prior art is strong, normality
Down easy moisture absorption and go bad.The present inventor has obtained a kind of hygroscopicity improvement by largely testing, and moisture, impurity content are low, surely
Qualitative good sildenafil citrate compound.
The preparation method of above-mentioned sildenafil citrate compound comprises the following steps：
Sildenafil citrate is dissolved in the in the mixed solvent of N- methylacetamides, chloroform；First with 30-50ml/min speed
Dichloromethane, ethanol, the mixed solvent of 1-METHYLPYRROLIDONE are added, it is stirring while adding, control 25-30 DEG C of temperature, growing the grain
0.5-1 hours；Then it is molten with the mixing of 20-25ml/min speed addition dichloromethane, ethanol, 1-METHYLPYRROLIDONE again
Agent, after growing the grain 3-5 hours, cooling, then it is kept stirring for 150-180 revs/min of stirring and crystallizing of speed, growing the grain 2-4 hours；Cross
Filter, is dried to obtain sildenafil citrate crystalline compounds.
Preferably, the volume of the mixed solvent of the N- methylacetamides, chloroform is sildenafil citrate weight
8-10 times, the volume ratio of N- methylacetamides and chloroform is 3:1.
Preferably, the volume total amount of the mixed solvent of the dichloromethane first added, ethanol, 1-METHYLPYRROLIDONE is Chinese holly
15-20 times of Sildena citrate weight, dichloromethane, ethanol, the volume ratio of 1-METHYLPYRROLIDONE are 5:3:1.
Preferably, it is citron to add dichloromethane, ethanol, the volume total amount of mixed solvent of 1-METHYLPYRROLIDONE
5-8 times of sour silaenafil weight, dichloromethane, ethanol, the volume ratio of 1-METHYLPYRROLIDONE are 3:2:1.
Preferably, the cooling is to be cooled to -5 DEG C with 20-25 DEG C/h of speed.
Preferably, the drying is 35-45 DEG C, is dried under reduced pressure.
The present inventor has obtained above-mentioned preparation method after substantial amounts of research has been carried out to it, has prepared a kind of difference
In the sildenafil citrate crystalline compounds of prior art, surprisingly found through overtesting, the compound crystal is obviously improved
Its hygroscopicity, moisture and impurity content are low, substantially increase its stability.
Brief description of the drawings：
Fig. 1 is the X-ray powder diffraction figure of sildenafil citrate compound prepared by embodiment 1.
Embodiment
The embodiment of the present invention is only limitted to be explained further and illustrates the present invention, not to present disclosure structure
Into limitation.
Embodiment 1：The preparation of sildenafil citrate compound
Sildenafil citrate is dissolved in 8 times of N- methylacetamides, the chlorine that 35 DEG C of volumes are sildenafil citrate weight
The volume ratio of imitative in the mixed solvent, N- methylacetamides and chloroform is 3:1；Volume total amount is first added with 30ml/min speed
For 15 times of dichloromethane of sildenafil citrate weight, ethanol, 1-METHYLPYRROLIDONE mixed solvent, dichloromethane,
Ethanol, the volume ratio of 1-METHYLPYRROLIDONE are 5:3:1, it is stirring while adding, control 25 DEG C of temperature, growing the grain 0.5 hour；Then again
5 times of dichloromethane, ethanol, N- methyl pyrrole of the volume total amount as sildenafil citrate weight are added using 20ml/min speed
The mixed solvent of pyrrolidone, dichloromethane, ethanol, the volume ratio of 1-METHYLPYRROLIDONE are 3:2:1, growing the grain is after 3 hours, with 20
DEG C/h speed be cooled to -5 DEG C, be then kept stirring for 150 revs/min of stirring and crystallizings of speed, growing the grain 2 hours；Filtering, 35
DEG C, be dried under reduced pressure to obtain sildenafil citrate crystalline compounds.
The X-ray powder diffraction obtained to prepared sildenafil citrate compound using Cu-K alpha ray measurements is composed
Figure is as shown in Figure 1.
Embodiment 2：The preparation of sildenafil citrate compound
Sildenafil citrate is dissolved in 9 times of N- methylacetamides, the chlorine that 40 DEG C of volumes are sildenafil citrate weight
The volume ratio of imitative in the mixed solvent, N- methylacetamides and chloroform is 3:1；Volume total amount is first added with 40ml/min speed
For 17.5 times of dichloromethane of sildenafil citrate weight, ethanol, 1-METHYLPYRROLIDONE mixed solvent, dichloromethane
Alkane, ethanol, the volume ratio of 1-METHYLPYRROLIDONE are 5:3:1, it is stirring while adding, control 27.5 DEG C of temperature, growing the grain 0.75 hour；
Then 6.5 times of dichloromethane of the volume total amount as sildenafil citrate weight, second are added using 22.5ml/min speed again
The mixed solvent of alcohol, 1-METHYLPYRROLIDONE, dichloromethane, ethanol, the volume ratio of 1-METHYLPYRROLIDONE are 3:2:1, growing the grain 4
After hour, -5 DEG C are cooled to 22.5 DEG C/h of speed, is then kept stirring for 165 revs/min of stirring and crystallizings of speed, growing the grain 3
Hour；Filtering, 40 DEG C, be dried under reduced pressure to obtain sildenafil citrate crystalline compounds.
The X-ray powder diffraction obtained to prepared sildenafil citrate compound using Cu-K alpha ray measurements is composed
Scheme similar to Example 1.
Embodiment 3：The preparation of sildenafil citrate compound
Sildenafil citrate is dissolved in 10 times of N- methylacetamides, the chlorine that 45 DEG C of volumes are sildenafil citrate weight
The volume ratio of imitative in the mixed solvent, N- methylacetamides and chloroform is 3:1；Volume total amount is first added with 50ml/min speed
For 20 times of dichloromethane of sildenafil citrate weight, ethanol, 1-METHYLPYRROLIDONE mixed solvent, dichloromethane,
Ethanol, the volume ratio of 1-METHYLPYRROLIDONE are 5:3:1, it is stirring while adding, control 30 DEG C of temperature, growing the grain 1 hour；Then again with
25ml/min speed adds 8 times of dichloromethane, ethanol, the N- methylpyrroles that volume total amount is sildenafil citrate weight
The mixed solvent of alkanone, dichloromethane, ethanol, the volume ratio of 1-METHYLPYRROLIDONE are 3:2:1, growing the grain is after 5 hours, with 25
DEG C/h speed be cooled to -5 DEG C, be then kept stirring for 180 revs/min of stirring and crystallizings of speed, growing the grain 4 hours；Filtering, 45
DEG C, be dried under reduced pressure to obtain sildenafil citrate crystalline compounds.
The X-ray powder diffraction obtained to prepared sildenafil citrate compound using Cu-K alpha ray measurements is composed
Scheme similar to Example 1.
Test example 1：Wettability test
This test example compares the sildenafil citrate of sildenafil citrate compound and prior art provided by the invention
Hygroscopicity.
Test method：Respectively under conditions of humidity 60% and 90%, room temperature, sample 1g is respectively taken to be placed on electronic balance, it is fixed
Shi Jilu weight, to detect moisture absorption degree, it the results are shown in Table 1.
Table 1, sample hygroscopicity measurement result
Wherein：
Sample 1：Sildenafil citrate made from the embodiment of the present invention 1；
Sample 2：Sildenafil citrate made from the embodiment of the present invention 2；
Sample 3：According to " sildenafil citrate improvement in synthesis "【Xiang Honglin, Hu Gaoyun, sildenafil citrates are waited to close
Into process modification, Hunan Medical college journal, 2000,2（1）：47-48】Method made from citric acid west ground that
Non- compound；
Sample 4, sildenafil citrate bulk drug imported product（Pfizer Ireland Pharmaceuticals）.
It is can be seen that from above-mentioned result of the test compared with the sildenafil citrate of prior art, it is provided by the present invention
Sildenafil citrate has the hygroscopicity being obviously improved.
Above-mentioned experiment is also carried out to the sildenafil citrate compound prepared by other embodiments of the present invention, it is obtained
Result it is similar.
Test example 2：Stability test
According to two annex X IX C of Chinese Pharmacopoeia version in 2010《Medicine stability test guideline》To citric acid west ground that
It is non-to have carried out study on the stability experiment.Selection traits, moisture, content, relevant material are that emphasis investigates project.
Sample 1：Sildenafil citrate made from the embodiment of the present invention 1；
Sample 2：Sildenafil citrate made from the embodiment of the present invention 2；
Sample 3：According to " sildenafil citrate improvement in synthesis "【Xiang Honglin, Hu Gaoyun, sildenafil citrates are waited to close
Into process modification, Hunan Medical college journal, 2000,2（1）：47-48】Method made from citric acid west ground that
Non- compound；
Sample 4, sildenafil citrate bulk drug imported product（Pfizer Ireland Pharmaceuticals）.
1st, accelerated test
Sample is taken, by commercially available back, in accelerated test（40 DEG C ± 2 DEG C of temperature, relative humidity 75% ± 5%）Under the conditions of place 6
Month, every quality index inspection result is shown in Table 2.
The accelerated test result of table 2
From accelerated test result, sample 3 and sample 4 have substantially through 6 months accelerated test moisture, content, relevant material
Change, and product of the present invention has no significant change through 6 months accelerated test characters, moisture, content, relevant material, and moisture and
About content of material well below sample 3 and sample 4, it can be seen that, the sildenafil citrate compound of present invention gained
Stability is good, and moisture, impurity content are low.
2nd, long term test
Sample is taken, by commercially available back, in long term test（30 DEG C ± 2 DEG C of temperature, relative humidity 65% ± 5%）Under the conditions of place 24
Month, every quality index inspection is had no significant change, and moisture is controlled below 1.0%, and relevant content of material is 0.15%
Hereinafter, well below sample 3 and 4, it can be seen that, the sildenafil citrate compound stability of present invention gained is good, moisture,
Impurity content is low.
Claims (1)
- A kind of 1. method for the sildenafil citrate compound for preparing treatment male erectile dysfunction, it is characterised in that including Following steps：Sildenafil citrate is dissolved in 9 times of the N- methyl vinyls that 40 DEG C of volumes are sildenafil citrate weight The volume ratio of the in the mixed solvent of amine, chloroform, N- methylacetamides and chloroform is 3:1；Body is first added with 40ml/min speed Product total amount be sildenafil citrate weight 17.5 times of dichloromethane, ethanol, the mixed solvent of 1-METHYLPYRROLIDONE, two Chloromethanes, ethanol, the volume ratio of 1-METHYLPYRROLIDONE are 5:3:1, it is stirring while adding, control 27.5 DEG C of temperature, growing the grain 0.75 Hour；Then 6.5 times of dichloromethane of the volume total amount as sildenafil citrate weight is added using 22.5ml/min speed again Alkane, ethanol, the mixed solvent of 1-METHYLPYRROLIDONE, dichloromethane, ethanol, the volume ratio of 1-METHYLPYRROLIDONE are 3:2:1, After growing the grain 4 hours, -5 DEG C are cooled to 22.5 DEG C/h of speed, be then kept stirring for 165 revs/min of stirring and crystallizings of speed, Growing the grain 3 hours；Filtering, 40 DEG C, be dried under reduced pressure to obtain sildenafil citrate crystalline compounds；X-ray powder diffraction figure such as Fig. 1 institutes that described sildenafil citrate compound is obtained using Cu-K alpha ray measurements Show.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711375487.1A CN107827895A (en) | 2015-07-23 | 2015-07-23 | A kind of method for the sildenafil citrate compound for preparing treatment male erectile dysfunction |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510436399.2A CN104974165B (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound for treating male erectile dysfunction |
| CN201711375487.1A CN107827895A (en) | 2015-07-23 | 2015-07-23 | A kind of method for the sildenafil citrate compound for preparing treatment male erectile dysfunction |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN201510436399.2A Division CN104974165B (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound for treating male erectile dysfunction |
Publications (1)
| Publication Number | Publication Date |
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| CN107827895A true CN107827895A (en) | 2018-03-23 |
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Family Applications (10)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711374500.1A Withdrawn CN107955009A (en) | 2015-07-23 | 2015-07-23 | A kind of method for the compound for preparing treatment male erectile dysfunction |
| CN201711329418.7A Withdrawn CN107903270A (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound for treating male erectile dysfunction |
| CN201711375487.1A Withdrawn CN107827895A (en) | 2015-07-23 | 2015-07-23 | A kind of method for the sildenafil citrate compound for preparing treatment male erectile dysfunction |
| CN201711327343.9A Pending CN107722018A (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound for treating male erectile dysfunction |
| CN201711329369.7A Pending CN107722020A (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound for treating male erectile dysfunction |
| CN201510436399.2A Active CN104974165B (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound for treating male erectile dysfunction |
| CN201711328270.5A Pending CN107880047A (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound |
| CN201711374498.8A Withdrawn CN107973799A (en) | 2015-07-23 | 2015-07-23 | The method for preparing the sildenafil citrate compound for the treatment of male erectile dysfunction |
| CN201711329368.2A Withdrawn CN107880048A (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound |
| CN201711327352.8A Pending CN107722019A (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound for treating male erectile dysfunction |
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| CN201711374500.1A Withdrawn CN107955009A (en) | 2015-07-23 | 2015-07-23 | A kind of method for the compound for preparing treatment male erectile dysfunction |
| CN201711329418.7A Withdrawn CN107903270A (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound for treating male erectile dysfunction |
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| CN201711327343.9A Pending CN107722018A (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound for treating male erectile dysfunction |
| CN201711329369.7A Pending CN107722020A (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound for treating male erectile dysfunction |
| CN201510436399.2A Active CN104974165B (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound for treating male erectile dysfunction |
| CN201711328270.5A Pending CN107880047A (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound |
| CN201711374498.8A Withdrawn CN107973799A (en) | 2015-07-23 | 2015-07-23 | The method for preparing the sildenafil citrate compound for the treatment of male erectile dysfunction |
| CN201711329368.2A Withdrawn CN107880048A (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound |
| CN201711327352.8A Pending CN107722019A (en) | 2015-07-23 | 2015-07-23 | A kind of sildenafil citrate compound for treating male erectile dysfunction |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1246478A (en) * | 1999-07-12 | 2000-03-08 | 广东天普生物化学制药有限公司 | Process for preparing Xidinafei |
| WO2000054777A1 (en) * | 1999-03-16 | 2000-09-21 | Pentech Pharmaceuticals, Inc. | Controlled release of sildenafil delivered by sublingual or buccal administration |
| CN1925860A (en) * | 2004-01-05 | 2007-03-07 | 特瓦制药工业有限公司 | Methods for the production of sildenafil base and citrate salt |
| WO2008074512A1 (en) * | 2006-12-21 | 2008-06-26 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Process for the preparation of sildenafil |
| CN101530400A (en) * | 2009-04-14 | 2009-09-16 | 李浪辉 | Effervescence tablet capable of treating penis erection dysfunction and preparation method thereof |
| WO2009125415A1 (en) * | 2008-04-07 | 2009-10-15 | Hetero Research Foundation | Amorphous form of sildenafil citrate |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9013750D0 (en) * | 1990-06-20 | 1990-08-08 | Pfizer Ltd | Therapeutic agents |
| CN104370915A (en) * | 2014-11-06 | 2015-02-25 | 成都医路康医学技术服务有限公司 | Preparation method of sildenafil citrate |
-
2015
- 2015-07-23 CN CN201711374500.1A patent/CN107955009A/en not_active Withdrawn
- 2015-07-23 CN CN201711329418.7A patent/CN107903270A/en not_active Withdrawn
- 2015-07-23 CN CN201711375487.1A patent/CN107827895A/en not_active Withdrawn
- 2015-07-23 CN CN201711327343.9A patent/CN107722018A/en active Pending
- 2015-07-23 CN CN201711329369.7A patent/CN107722020A/en active Pending
- 2015-07-23 CN CN201510436399.2A patent/CN104974165B/en active Active
- 2015-07-23 CN CN201711328270.5A patent/CN107880047A/en active Pending
- 2015-07-23 CN CN201711374498.8A patent/CN107973799A/en not_active Withdrawn
- 2015-07-23 CN CN201711329368.2A patent/CN107880048A/en not_active Withdrawn
- 2015-07-23 CN CN201711327352.8A patent/CN107722019A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000054777A1 (en) * | 1999-03-16 | 2000-09-21 | Pentech Pharmaceuticals, Inc. | Controlled release of sildenafil delivered by sublingual or buccal administration |
| CN1246478A (en) * | 1999-07-12 | 2000-03-08 | 广东天普生物化学制药有限公司 | Process for preparing Xidinafei |
| CN1925860A (en) * | 2004-01-05 | 2007-03-07 | 特瓦制药工业有限公司 | Methods for the production of sildenafil base and citrate salt |
| WO2008074512A1 (en) * | 2006-12-21 | 2008-06-26 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Process for the preparation of sildenafil |
| WO2009125415A1 (en) * | 2008-04-07 | 2009-10-15 | Hetero Research Foundation | Amorphous form of sildenafil citrate |
| CN101530400A (en) * | 2009-04-14 | 2009-09-16 | 李浪辉 | Effervescence tablet capable of treating penis erection dysfunction and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 宫平等，: ""柠檬酸西地那非的合成"", 《沈阳药科大学学报》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107880048A (en) | 2018-04-06 |
| CN107973799A (en) | 2018-05-01 |
| CN107903270A (en) | 2018-04-13 |
| CN107722019A (en) | 2018-02-23 |
| CN104974165A (en) | 2015-10-14 |
| CN107722020A (en) | 2018-02-23 |
| CN107880047A (en) | 2018-04-06 |
| CN107722018A (en) | 2018-02-23 |
| CN107955009A (en) | 2018-04-24 |
| CN104974165B (en) | 2017-12-01 |
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Application publication date: 20180323 |