CN111518093A - 一种检测硫化物的荧光探针及其制备和应用 - Google Patents
一种检测硫化物的荧光探针及其制备和应用 Download PDFInfo
- Publication number
- CN111518093A CN111518093A CN202010313442.7A CN202010313442A CN111518093A CN 111518093 A CN111518093 A CN 111518093A CN 202010313442 A CN202010313442 A CN 202010313442A CN 111518093 A CN111518093 A CN 111518093A
- Authority
- CN
- China
- Prior art keywords
- fluorescent probe
- sulfide
- detecting
- compound
- solution
- 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
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
- G01N21/643—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" non-biological material
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1007—Non-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
- C09K2211/1037—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom with sulfur
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1088—Heterocyclic compounds characterised by ligands containing oxygen as the only heteroatom
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N2021/6417—Spectrofluorimetric devices
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Optics & Photonics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Plasma & Fusion (AREA)
- Materials Engineering (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
本发明公开了一种检测硫化物的荧光探针及其制备和应用,本发明选择性高,能够特异性识别溶液中的硫化物;抗干扰能力强,能够防止环境中其他物质对探针检测的干扰;灵敏度高,适合微量硫化物的检测;反应快速,颜色变化明显,合成简单,性质稳定,有广阔的应用前景。本发明的荧光探针可经简单化学合成获得,制备成本低,易于推广。
Description
技术领域
本发明涉及化学检测技术中的小分子荧光染料的制备,具体涉及一种基于近红外半菁染料检测硫化物的荧光探针及其合成方法。
背景技术
硫化物是表示水体质量的重要参数之一,广泛存在于环境、水体及生活工业废液中,硫化物有毒害,吸入硫化氢,会造成细胞缺氧,低浓度就会引起身体不适,具体表现为眼刺痛、流泪、流涕、咽喉痛、头痛、头晕、恶心等症状,因此检测硫化物具有重要意义。现行施工用水检测中硫化物的检测采用硫酸盐重量法(《GB 11899-89水质硫酸盐的测定重量法》),此方法步骤多,测量前需预处理水样,陈化沉淀甚至需要过夜,且对试验人员要求较高。水泥、矿粉、粉煤灰,粗细骨料等施工材料的三氧化硫测定同样操作繁琐(《GB/T 176-2017水泥化学分析方法》)。
得益于这些年荧光成像技术的发展,荧光成像分析法具有灵敏度高、选择性好、响应迅速、操作简单等优点,对生物样品基本没损伤,已开始用于生物体内的小分子检测,并未用于施工材料的检测,而且很多探针合成复杂,容易受到干扰离子影响。因此开发具有高选择性、高灵敏度、光稳定性好,能够实时快速检测硫化物的荧光开启型近红外荧光探针具有重要的实用价值。
发明内容
本发明目的在于针对目前检测硫化物荧光探针现有技术中存在的问题,提供一种能够检测水中硫化物的近红外荧光探针及其制备方法和应用,该荧光探针合成简单、能快速、灵敏专一检测溶液中的硫化物。
本发明的技术方案:
一种检测硫化物的近红外荧光探针,结构通式如下:
一种所述硫化物近红外荧光探针的制备方法,制备流程如下所示:
具体制备步骤如下:
1)化合物1与间苯二酚于碳酸钾的乙腈溶液中加热反应,分离、提纯得化合物2:
2)化合物2、2,4-二硝基氟苯和碳酸铯于二氯甲烷溶液中反应,分离、提纯得到紫色粉末,即检测硫化物的荧光探针3:
步骤(1)中,所述化合物1、间苯二酚、碳酸钾的物质的量比为1:2:2;所述化合物1即七甲川苯并噻唑花菁染料与溶剂乙腈的重量比为1:6-7;所述碳酸钾和间苯二酚总重量与溶剂乙腈的重量比为1:14-15。
步骤(1)中,所述加热温度为60℃,反应时间为5h。
步骤(1)中分离提纯步骤为,将上述反应液进行抽滤,滤液经减压蒸馏浓缩得到粗产品。粗产品通过柱层层析硅胶进行分离、提纯,所用洗脱剂为体积比为100:1-5的二氯甲烷-甲醇混合液。
步骤(2)中,所述化合物2、2,4-二硝基氟苯、碳酸铯的物质的量比为1:4:1。
步骤(2)中,所述反应时间为12h。
步骤(2)中,所述分离提纯步骤为将反应液于真空下减压浓缩后,用柱层析纯化;洗脱液为为100:1-5的二氯甲烷-甲醇混合液。
一种上述近红外荧光探针在检测硫化物的应用。该探针可以用于溶液等体系中硫化物浓度的定量检测。
上述应用中,激发波长为680nm,检测波长为735nm。
本发明的优点和有益效果:
本发明设计并合成了一种近红外荧光探针3。所制备的探针可以实现对硫化物选择性与灵敏度的近红外荧光信号快速开启型识别。选择性高,能够特异性识别溶液中的硫化物;抗干扰能力强,能够防止环境中其他物质对探针检测的干扰;灵敏度高,适合微量硫化物的检测;反应快速,颜色变化明显,合成简单,性质稳定,有广阔的应用前景。
附图说明
图1是荧光探针3的结构;
图2是荧光探针加入不同分析物的荧光光谱,插图为加入硫化物溶液颜色变化;
图3是硫化物试纸条变化。
具体实施方式
下面结合实施例和附图对本发明做进一步说明,但本发明不受下述实施例的限制。
实施例1、化合物2的制备路线如下:
具体制备步骤如下:
在室温搅拌、氩气保护下,将染料1(579mg,1mmol)、碳酸钾(276mg,2mmol)和间苯二酚(220mg,2mmol)溶于乙腈(10mL)中,于60℃加热反应5小时,反应结束后冷却至室温得到反应液。再将反应液抽滤,滤液经减压蒸馏浓缩得到粗产品。粗产品用柱层层析硅胶进行分离、提纯,所用洗脱剂为体积比为100:1-5的二氯甲烷-甲醇混合液,得到目标产物2,为深蓝色固体,产率为81%。1H NMR(400MHz,DMSO-d6,ppm):δ8.27(1H),8.21(1H),8.04(1H),7.73(1H),7.61(1H),7.34(1H),7.25(1H),6.82(1H),6.77(1H),6.73(1H),4.74-4.68(2H),2.66-2.62(4H),1.80(2H),1.38(3H);13C NMR(100MHz,DMSO-d6,ppm):δ169.66,161.51,158.41,154.28,142.60,141.49,131.64,129.39,129.17,127.53,127.32,126.03,124.28,115.75,114.49,114.14,112.35,105.07,102.36,43.43,28.97,24.78,20.56,13.91;HRMS(ESI):calcd.for C24H22NO2S+[M]+:388.1366,Found:388.1391。
实施例2、探针3的制备路线如下:
其具体制备步骤如下:
称取化合物2(95mg,0.2mmol)溶于干燥二氯甲烷(5mL)中,通入氩气搅拌5min,加入2,4-二硝基氟苯(94uL,0.8mmol)及碳酸铯(65mg,0.2mmol)后,室温搅拌过夜。反应液经减压蒸馏浓缩得到粗产物,粗产品用柱层层析硅胶进行分离、提纯,所用洗脱剂为体积比为100:1-5的二氯甲烷-甲醇混合液,得到目标产物3,为紫色固体,产率为16%。m.p.190-192℃.1H NMR(400MHz,DMSO-d6,ppm):δ8.96(d,J=2.8Hz,1H),8.53-8.50(m,1H),8.36-8.32(d,J=14.8Hz,1H),8.24-8.23(d,J=8.0Hz,1H),8.18-8.14(d,J=8.8Hz,1H),7.81-7.77(m,1H),7.70-7.66(m,1H),7.60-7.59(d,J=8.0Hz,1H),7.42-7.40(m,2H),7.24(s,1H),7.18-7.158(m,1H),7.05-7.02(d,J=14.8Hz,1H),4.83-4.78(m,2H),2.70-2.67(m,4H),1.84-1.81(t,J=4.6Hz,2H),1.42-1.39(t,J=7.0Hz,3H);13C NMR(100MHz,DMSO-d6,ppm):δ170.64,156.86,156.17,155.70,154.45,153.67,142.68,142.58,141.49,140.31,130.22,130.18,129.67,129.53,128.31,128.14,127.81,124.31,122.44,120.89,120.08,116.36,114.28,113.32,108.02,43.99,29.23,24.64,20.37,14.16.HRMS:(C30H24N3O6S+)m/z:计算值[M]+:554.1380.实测值[M]+:554.1400.
探针3的荧光检测应用:
将探针配成浓度为5.0×10-3mol/L的DMSO溶液,避光保存备用。检测方法如下:
1)探针3的选择性检测
分别将探针在磷酸缓冲溶液(含25%乙醇,10mM,pH=7.4)中配置成1×10-5mol/L的待测液3mL,然后分别加入1×10-4mol/L的不同分析物(K+,Na+Cu2+,Mg2+,Ca2+,Hg2+,Fe3+,F-,Cl-,Br-,I-,SO4 2-,SO3 2-,HSO3 -,HSO4 -,HCO3 -,H2PO4 -,P2O7 4-,ClO4 -,ClO-,OAc-,NO3 2-,NO2 -,H2O2,,Na2S,柠檬酸钠),以680nm波长激发,测试各溶液荧光发射光谱,比较735nm处的荧光强度。由图2可知,只有硫化钠可以导致溶液产生显著的荧光变化,而加入其他小分子时溶液的荧光基本没有变化,这表示该探针能专一识别硫化钠,且基本不受干扰。
2)探针3用于实际检测
配制含微量硫化钠的溶液,滴在探针试纸条上,观察试纸条颜色变化,如图3所示,在试纸上观察到明显的紫色变成蓝色。
以上内容是结合具体的实施方式对本发明所作的进一步详细说明,不能认定本发明的具体实施只局限于这些说明,对于本发明所属技术领域的普通技术人员来说,在作为荧光探针是本发明新荧光染料的一种用途,不能认定本发明的化合物仅用于荧光探针。
Claims (8)
3.根据权利要求2所述的一种检测硫化物的近红外荧光探针制备方法,其特征在于,步骤(1)中,所述化合物1、间苯二酚、碳酸钾的物质的量比为1:2:2;步骤(2)中,所述化合物2、2,4-二硝基氟苯、碳酸铯的物质的量比为1:4:1。
4.根据权利要求2所述的一种检测硫化物的近红外荧光探针,其特征在于,步骤(1)中,所述加热温度为60℃,反应时间为5h;步骤(2)中,反应时间为12h。
5.根据权利要求2所述的一种检测硫化物的近红外荧光探针,其特征在于,步骤(1)中,所述分离提纯步骤为将反应液在真空下减压浓缩成粗产物,用柱层析纯化;所用洗脱液为体积比100:1-5的二氯甲烷-甲醇的混合溶液。
6.根据权利要求2所述的一种检测硫化物的近红外荧光探针,其特征在于,步骤(2)中,所述分离提纯步骤为将反应液在真空下减压浓缩成粗产物,用柱层析纯化;所用洗脱液为体积比100:1-5的二氯甲烷-甲醇的混合溶液。
7.一种如权利要求1所述荧光探针的用途,其特征在于,所述荧光探针用于检测水中的硫化物。
8.根据权利要求7所述的应用,其特征在于,荧光探针的激发波长为680nm,发射波长为735nm。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010313442.7A CN111518093A (zh) | 2020-04-20 | 2020-04-20 | 一种检测硫化物的荧光探针及其制备和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010313442.7A CN111518093A (zh) | 2020-04-20 | 2020-04-20 | 一种检测硫化物的荧光探针及其制备和应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN111518093A true CN111518093A (zh) | 2020-08-11 |
Family
ID=71904004
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010313442.7A Pending CN111518093A (zh) | 2020-04-20 | 2020-04-20 | 一种检测硫化物的荧光探针及其制备和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111518093A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113149931A (zh) * | 2021-03-18 | 2021-07-23 | 赣南医学院 | 一种硫负离子荧光探针材料及其制备方法和应用 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102115610A (zh) * | 2010-01-05 | 2011-07-06 | 大连理工大学 | 一类荧光染料、制备方法及其应用 |
CN104946240A (zh) * | 2015-05-28 | 2015-09-30 | 中国科学院海洋研究所 | 一种硫化物荧光探针及其制备方法 |
CN108329302A (zh) * | 2018-03-22 | 2018-07-27 | 中国药科大学 | 一种硫化物特异性响应的半花菁类近红外荧光探针化合物及其制备方法和应用 |
CN110128418A (zh) * | 2019-06-27 | 2019-08-16 | 许昌学院 | 一种基于半花菁结构衍生物的近红外荧光探针及其制备方法和应用 |
CN110724114A (zh) * | 2018-07-16 | 2020-01-24 | 北京工商大学 | 一种检测亚硫酸氢根及硫化氢的荧光探针 |
-
2020
- 2020-04-20 CN CN202010313442.7A patent/CN111518093A/zh active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102115610A (zh) * | 2010-01-05 | 2011-07-06 | 大连理工大学 | 一类荧光染料、制备方法及其应用 |
CN104946240A (zh) * | 2015-05-28 | 2015-09-30 | 中国科学院海洋研究所 | 一种硫化物荧光探针及其制备方法 |
CN108329302A (zh) * | 2018-03-22 | 2018-07-27 | 中国药科大学 | 一种硫化物特异性响应的半花菁类近红外荧光探针化合物及其制备方法和应用 |
CN110724114A (zh) * | 2018-07-16 | 2020-01-24 | 北京工商大学 | 一种检测亚硫酸氢根及硫化氢的荧光探针 |
CN110128418A (zh) * | 2019-06-27 | 2019-08-16 | 许昌学院 | 一种基于半花菁结构衍生物的近红外荧光探针及其制备方法和应用 |
Non-Patent Citations (1)
Title |
---|
LONGBIN XU等: "A novel near-infrared fluorescent probe for detecting intracellular alkaline phosphatase and imaging of living cells", 《J. MATER. CHEM. B》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113149931A (zh) * | 2021-03-18 | 2021-07-23 | 赣南医学院 | 一种硫负离子荧光探针材料及其制备方法和应用 |
CN113149931B (zh) * | 2021-03-18 | 2023-04-28 | 赣南医学院 | 一种硫负离子荧光探针材料及其制备方法和应用 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Peng et al. | A novel fluorescent probe for selective detection of hydrogen sulfide in living cells | |
CN109535147B (zh) | 一种快速响应的甲醛荧光探针及其制备方法和应用 | |
CN114591633B (zh) | 一类氧杂蒽-半花菁近红外荧光染料,其合成方法及应用 | |
CN113121520B (zh) | 一种具有aie+esipt+ict机制的荧光染料和荧光探针及其制备方法与应用 | |
CN110092773B (zh) | 一种氧杂蒽类衍生物及其制备方法和应用 | |
CN109942508B (zh) | 一种比率型一氧化碳荧光探针及其制备方法和应用 | |
CN111518093A (zh) | 一种检测硫化物的荧光探针及其制备和应用 | |
CN112794847B (zh) | 一种顺序检测水合肼和亚硫酸氢根的新型荧光探针及其合成及应用 | |
CN111285836A (zh) | 一种近红外荧光探针的制备和应用 | |
CN111233928B (zh) | 一种香豆素衍生物Mito-Cys及其制备方法和应用 | |
CN108558839B (zh) | 一种香豆素-吡啶化合物,制备方法及其应用 | |
CN107831165B (zh) | 一种双通道铜离子检测试纸及其制备方法 | |
CN113121541B (zh) | 一种同时区分金离子Au3+与钯的荧光探针的合成及应用 | |
CN113201132B (zh) | 一种基于单分散四臂聚乙二醇的罗丹明b衍生物荧光探针分子及其制备方法 | |
Wu et al. | A lysosome-targeting colorimetric and fluorescent dual signal probe for sensitive detection and bioimaging of hydrogen sulfide | |
CN112225743B (zh) | 一种喹啉基近红外罗丹明荧光染料、比率荧光探针及其合成和应用 | |
CN111592532A (zh) | 一种检测肼的近红外荧光探针及其制备和应用 | |
CN111413308B (zh) | 一种稀土元素配合物在检测矿泉水中微量亚硝酸根的应用 | |
CN109574921B (zh) | 一种检测醋酸根离子的荧光探针及其制备方法和使用方法 | |
CN110229203B (zh) | 一种氨基己糖酶荧光探针及其制备方法和应用 | |
CN114957180A (zh) | 一种基于双激发波长荧光分析法识别pH值的荧光探针及其制备方法和应用 | |
CN108760707B (zh) | 一种探针试剂的应用 | |
CN110156858B (zh) | 一种水溶性硫化氢荧光探针及其制备方法和其在水质硫化物及细胞硫化氢检测中的应用 | |
Sun et al. | A novel fluorescent probe based on triphenylamine for detecting sulfur dioxide derivatives | |
CN109134483B (zh) | 一种硫化氢荧光探针及其制备方法和应用 |
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 | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200811 |
|
RJ01 | Rejection of invention patent application after publication |