CN109988333B - 一种聚苯乙烯微球 - Google Patents
一种聚苯乙烯微球 Download PDFInfo
- Publication number
- CN109988333B CN109988333B CN201910272776.1A CN201910272776A CN109988333B CN 109988333 B CN109988333 B CN 109988333B CN 201910272776 A CN201910272776 A CN 201910272776A CN 109988333 B CN109988333 B CN 109988333B
- Authority
- CN
- China
- Prior art keywords
- microsphere
- polystyrene
- stirring
- microspheres
- polyacrylic resin
- 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.)
- Active
Links
- 239000004005 microsphere Substances 0.000 title claims abstract description 98
- 239000004793 Polystyrene Substances 0.000 title claims abstract description 47
- 229920002223 polystyrene Polymers 0.000 title claims abstract description 47
- 239000004925 Acrylic resin Substances 0.000 claims abstract description 15
- 229920003134 Eudragit® polymer Polymers 0.000 claims abstract description 12
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000003756 stirring Methods 0.000 claims description 22
- 239000002245 particle Substances 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 239000012456 homogeneous solution Substances 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 12
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical group C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 9
- 229920003135 Eudragit® L 100-55 Polymers 0.000 claims description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 8
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 8
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 claims description 8
- 239000006228 supernatant Substances 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 5
- 239000006185 dispersion Substances 0.000 claims description 5
- 239000011261 inert gas Substances 0.000 claims description 5
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 2
- 238000001179 sorption measurement Methods 0.000 abstract description 18
- 238000012986 modification Methods 0.000 abstract description 4
- 230000004048 modification Effects 0.000 abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000002202 Polyethylene glycol Substances 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 238000005303 weighing Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000002296 dynamic light scattering Methods 0.000 description 4
- 238000003921 particle size analysis Methods 0.000 description 4
- 239000004342 Benzoyl peroxide Substances 0.000 description 3
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 3
- 229920003139 Eudragit® L 100 Polymers 0.000 description 3
- 235000019400 benzoyl peroxide Nutrition 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000012674 dispersion polymerization Methods 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 239000003999 initiator Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 3
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000009210 therapy by ultrasound Methods 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- CDOUZKKFHVEKRI-UHFFFAOYSA-N 3-bromo-n-[(prop-2-enoylamino)methyl]propanamide Chemical compound BrCCC(=O)NCNC(=O)C=C CDOUZKKFHVEKRI-UHFFFAOYSA-N 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229960000878 docusate sodium Drugs 0.000 description 1
- 238000010556 emulsion polymerization method Methods 0.000 description 1
- 238000007720 emulsion polymerization reaction Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229920001002 functional polymer Polymers 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 230000005661 hydrophobic surface Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 1
- 125000005395 methacrylic acid group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010558 suspension polymerization method Methods 0.000 description 1
- 238000010557 suspension polymerization reaction Methods 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 238000004506 ultrasonic cleaning Methods 0.000 description 1
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/14—Polymerisation; cross-linking
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F112/00—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
- C08F112/02—Monomers containing only one unsaturated aliphatic radical
- C08F112/04—Monomers containing only one unsaturated aliphatic radical containing one ring
- C08F112/06—Hydrocarbons
- C08F112/08—Styrene
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/12—Chemical modification
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2325/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring; Derivatives of such polymers
- C08J2325/02—Homopolymers or copolymers of hydrocarbons
- C08J2325/04—Homopolymers or copolymers of styrene
- C08J2325/06—Polystyrene
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2433/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers
- C08J2433/02—Homopolymers or copolymers of acids; Metal or ammonium salts thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2433/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers
- C08J2433/04—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters
- C08J2433/06—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters of esters containing only carbon, hydrogen, and oxygen, the oxygen atom being present only as part of the carboxyl radical
- C08J2433/08—Homopolymers or copolymers of acrylic acid esters
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Polymers & Plastics (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- Dispersion Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
本发明提供一种聚苯乙烯微球,所述聚苯乙烯微球是微米或纳米级别,所述微球表面包被聚丙烯酸树脂Eudragit。本发明的聚苯乙烯微球是一种非特异性吸附非常低的聚苯乙烯微球,微球表面含有功能性基团羧基,无需再对聚苯乙烯微球表面进一步功能修饰,进一步大幅简化操作,降低损耗。
Description
技术领域
本发明属于功能高分子材料技术领域,具体涉及一种聚苯乙烯微球。
背景技术
聚苯乙烯微球由于制备方法简单,容易放大生产,而且无毒,表面容易修饰不同的功能基团等特性,在医学、生物化学、免疫测定以及分子生物学等诸多领域具有广泛的应用,常用来作为生物芯片的载体微球。
目前,制备聚苯乙烯微球的方法主要有乳液聚合法、分散聚合法以及悬浮聚合法等,这些方法各有特点,很多学者针对不同的应用领域已对这些方法进行了研究。这些方法中,乳液聚合法可以用来制备单分散性较好的聚苯乙烯微球,微球粒径通常是纳米和纳米级,若需要制备尺寸较大的微米级复合微球,通常会采用分散聚合法、悬浮聚合法,然后对微球的表面进一步修饰功能基团,应用于不同领域中。
但在应用过程中,由于聚苯乙烯是疏水性聚合物,通过直接微球表面存在较严重的非特异性蛋白质吸附现象,导致分析平台的灵敏度和选择性降低,在免疫检测时,非特异性吸附会使背景增加,降低检测的灵敏度。特别是在实际应用中,待测样本通常是具有复杂组成的混合物,非特异性吸附带来的影响更大,因此研究者一直在尝试不同的方法来降低微球表面的非特异性吸附。
为了达到降低非特异性吸附的目的,研究者一般对微球基质的表面或蛋白质外表进行改性和处理,因为蛋白质的结构多变而复杂,一般不是通过简单的处理就能达到效果的,所以通常对微球的表面进行改性。其中,聚乙二醇(PEG)常被用来处理微球表面,因为PEG具有很好的亲水性,可以在微球表面和蛋白质之间产生排斥作用,降低微球表面的非特异性吸附。但因为大部分的微球基质是疏水性的,PEG同这些基质的集合能力很差,所以PEG的表面改性效率较低。为了提高PEG与微球表面的结合能力,一些研究者对PEG进行改性,这某种程度上增加了技术难度和工作量,另外,直接在微球表面进行PEG聚合也被证明不是特别有效的方法。
发明内容
为了解决上述问题,本发明提供一种聚苯乙烯微球,所述聚苯乙烯微球是微米或纳米级别,所述微球表面包被聚丙烯酸树脂Eudragit。
聚丙烯酸树脂Eudragit是合成药用辅料的商品名,它包括甲基丙烯酸共聚物和甲丙烯酸酯共聚物,在中国通称为丙烯酸树脂。Eudragit L100-55是甲基丙烯酸和丙烯酸乙酯(1:1)共聚物,Eudragit L100是甲基丙烯酸和丙烯酸乙酯(1:1)共聚物;聚合物组成中甲基丙烯酸单元占比46%~50.6%,聚合物结构单元如下图所示,聚合物链含有大量的亲水性基团羧基,可以作为分散聚合过程中的稳定剂,包覆在微球表面,有效的稳定微球和降低微球表面的非特异性吸附。聚合物Eudragit L100-55和 Eudragit L100的结构单元分子式如下,式1是Eudragit L100-55结构单元分子式,式2是Eudragit L100结构单元分子式。
聚丙烯酸树脂Eudragit广泛用于药物制剂的胃溶包衣、肠溶包衣、缓控释包衣、保护隔离包衣、缓释骨架材料和经皮给药制剂的骨架胶粘材料。
在一种实施方式中,所述聚丙烯酸树脂Eudragit是聚丙烯酸树脂Eudragit L100-55或L100。
在一种实施方式中,所述聚苯乙烯微球是纳米聚苯乙烯微球,其通过以下方式制备:将十二烷基硫酸钠或十二烷基磺酸钠溶解在纯水中,搅拌得到均相溶液;然后引入苯乙烯单体继续进行搅拌,然后将溶解有过硫酸铵或过硫酸钾的水溶液加入所述均相溶液中;惰性气体保护下,于68~72℃条件下搅拌反应,反应结束后离心处理,去除上清液,采用纯水分散,得到单分散的纳米级聚苯乙烯微球;用氢氧化钾或氢氧化钠溶液溶解聚丙烯酸树脂Eudragit得到均相溶液,将该溶液加入到微球的分散液中,搅拌混合均匀,调整混合液的PH值到5.0~6.5,检测微球粒径,确保微球没有聚集,继续搅拌10~12小时,离心处理,去上清液,用水分散得到所述纳米聚苯乙烯微球。
在一种实施方式中,所述聚苯乙烯微球是微米聚苯乙烯微球,其通过以下方式制备:将聚丙烯酸树脂Eudragit、磺基丁二酸钠二辛酯、乙醇和乙二醇甲醚加入反应容器,搅拌得到均相溶液;将引发剂过氧化苯甲酰或偶氮二异丁腈溶解于苯乙烯单体中,然后将溶解有引发剂的苯乙烯加入所述均相溶液中;惰性气体保护下,于70~80℃条件下搅拌反应;反应结束后分别依次采用乙醇和水作为分散剂进行分散,最终得到低非特异性吸附微米级聚苯乙烯微球。
本发明的聚苯乙烯微球是一种非特异性低吸附聚苯乙烯微球。本发明的微球表面含有功能性基团羧基,无需再对聚苯乙烯微球表面进一步功能修饰,进一步大幅简化操作,降低损耗。本发明中聚丙烯酸树脂Eudragit是一种分子链较长的聚合物,可以使聚合物和载体微球之间实现多位点结合,使结合的聚合物不容易脱落,同时大量的亲水性基团在微球表面和蛋白质之间可以提供较大的空间位阻,抑制其它带有疏水性的物质接近,使得到的微球的表面具有主动抑制非特异性吸附的性质。更为重要的是此亲水性基团为羧基,无需对微球表面进一步修饰,就能够应用于不同领域。
本发明微球制备操作简便,适于产业化推广使用,并且最关键的是可以制备获得单分散的、粒径高度均匀的非特异性吸附聚苯乙烯微球,为聚苯乙烯微球在医学、生物化学、免疫测定以及分子生物学等领域的应用做好了基础准备工作。
附图说明
为了更清楚地说明本申请实施例中的技术方案,下面将对实施例中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本申请中记载的一些实施例,对于本领域普通技术人员来说,在不付出创造性劳动的前提下,还可以根据这些附图获得其它的附图。
图1是本发明实施例1中的低非特异性吸附纳米级聚苯乙烯微球的动态激光散射粒度分析数据图;
图2是本发明实施例2中的低非特异性吸附纳米级聚苯乙烯微球的动态激光散射粒度分析数据图;
图3是本发明实施例3中一步法制得的低非特异性吸附微米级聚苯乙烯微球的电镜扫描图;和
图4是本发明未包被聚苯乙烯微球在全血和血清中应用的相关性图;
图5是本发明包被聚苯乙烯微球在全血和血清中应用的相关性图。
具体实施方式
为了使本领域技术领域人员更好地理解本申请中的技术方案,下面将结合下面结合实施例对本发明作进一步说明,显然,所描述的实施例仅仅是本申请一部分实施例,而不是全部的实施例。基于本申请中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其它实施例,都应当属于本申请保护的范围。
实施例1:本发明第一种纳米级聚苯乙烯微球的制备
本实施例提供本发明第一种纳米级聚苯乙烯微球的制备方法,具体制备步骤如下:
聚苯乙烯微球的合成:取250ml的圆底烧瓶,加入86.38g纯水,43mg十二烷基硫酸钠,惰性气体保护下,于70℃条件下搅拌得到均相溶液;加入苯乙烯单体12.91g,继续搅拌1小时,称取10mg过硫酸铵溶解在水中,加入上面所得均相溶液中,温度70℃,150rpm下反应6小时;离心处理,去除上清液,最终分散于100ml纯水中,制备获得平均粒径为158nm的单分散聚苯乙烯微球。
聚苯乙烯微球的包被:在200ml烧杯中,称量2.5g Eudragit L100-55溶解于100ml0.5M的氢氧化钾溶液中,搅拌状态下,加入第一步合成的聚苯乙烯微球分散液,搅拌30分钟;充分混匀后,将一定量的0.1M的盐酸溶液滴加到上述反应体系中,调整体系的PH值为6.0,室温搅拌12小时,检测粒径,无并集现象发生。超声波清洗仪超声10min后,再用纯水清洗,最终定容至100ml。用动态激光散射粒度分析方法测定包被后的微球粒径,具体结果如图1所示,从图1中测量数据可见,微球平均粒径为180.9nm,微球粒径方差(Variance(P.I.))为0.012,标准偏差为19.9nm;从图1中可以看出本发明包被后的微球粒径大小均匀,均一性好,修饰后的羧基包覆微球整个疏水表面,具有很好的亲水性。
实施例2:本发明第二种纳米级聚苯乙烯微球的制备
聚苯乙烯微球的合成:取500ml的圆底烧瓶,加入200g纯水,碳酸钾0.1g,惰性气体保护下,于70℃条件下搅拌得到均相溶液;加入苯乙烯单体37.5g,丙烯酸1.2g,继续搅拌1小时,称取300mg过硫酸铵溶解在水中,加入上面所得均相溶液中,温度70℃,150rpm下反应20小时;离心处理,去除上清液,最终分散于300ml纯水中,粒径为581nm的单分散聚苯乙烯微球。
聚苯乙烯微球的包被:在1000ml烧杯中,称量8.0g Eudragit L100-55溶解于300ml 0.5M的氢氧化钾溶液中,搅拌状态下,加入第一步合成的聚苯乙烯微球分散液,搅拌30分钟;充分混匀后,将一定量的0.1M的盐酸溶液滴加到上述反应体系中,调整体系的PH值为6.0,室温搅拌12小时,检测粒径,无并集现象发生。超声波清洗仪超声10min后,再用纯水清洗,最终定容至300ml,检测粒径用动态激光散射粒度分析方法测定包被后的微球粒径,具体结果如图1所示,从图2中测量数据可见,微球平均粒径为微球平均粒径为618.3nm,微球粒径方差(Variance(P.I.))为0.008,标准偏差为56.3nm;从图2中可以看出本发明包被后的微球粒径大小均匀,均一性好。
实施例3:本发明第三种微米级聚苯乙烯微球的制备
本实施例提供一种低非特异性吸附微米级聚苯乙烯微球的制备方法,具体步骤如下:
取500ml的圆底烧瓶,加入12g Eudragit L100-55、6g磺基丁二酸钠二辛酯、100mL乙醇和200mL乙二醇甲醚,搅拌得到均相溶液;称取3.1g过氧化苯甲酰作为引发剂溶解于62mL蒸馏的苯乙烯单体中;将溶解有过氧化苯甲酰的苯乙烯单体溶液加入上面所得均相溶液中,搅拌,通氮气保护,反应温度70℃,150rpm下反应20小时;离心处理,去除上清液,再用乙醇分散,重复分散六次,最终分散于200mL纯水中,得到粒径为4.5μm的低非特异性吸附微米级聚苯乙烯微球。
实施例4:本发明纳米级聚苯乙烯微球的应用
本实施案例是用本制备方法实施例1得到经过包被和不包被供氧微球和受氧微球的比对。实验方案如下:
用本公司LIA-12均相化学发光免疫分析仪进行检测,仪器将自动进行以下操作,在反应杯中,加入50μL CRP不同浓度临床样本(包含血清和全血),每孔平行3管取均值,50μL生物素化抗CRP抗体,50μL偶联抗CRP抗体的受氧微球,37℃反应7.5min,继续加入50μL偶联链霉亲和素的供氧微球,37℃反应5min,进行检测。实验结果如下表和图4-5中所示。从表和图中可以看出,包被微球中血清和全血的相关性系数达到0.9927,而未包被中血清和全血的相关性系数为0.9372,从该实验结果表明包被后的微球使得样品中非特异吸附大大降低,使得包被后的微球血清和全血的测量结果之间具有非常好的相关性,包被后的微球对于样品的适应性大大增强,可以直接用于全血样品检测。
应该理解到披露的本发明不仅仅限于描述的特定的方法、方案和物质,因为这些均可变化。还应理解这里所用的术语仅仅是为了描述特定的实施方式方案的目的,而不是意欲限制本发明的范围,本发明的范围仅受限于所附的权利要求。
本领域的技术人员还将认识到,或者能够确认使用不超过常规实验,在本文中所述的本发明的具体的实施方案的许多等价物。这些等价物也包含在所附的权利要求中。
Claims (3)
1.一种表面包被聚丙烯酸树脂Eudragit的纳米聚苯乙烯微球的制备方法,其特征在于,所述方法包括:将十二烷基硫酸钠或十二烷基磺酸钠溶解在纯水中,搅拌得到均相溶液;然后引入苯乙烯单体继续进行搅拌,然后将溶解有过硫酸铵或过硫酸钾的水溶液加入所述均相溶液中;惰性气体保护下,于68~72℃条件下搅拌反应,反应结束后离心处理,去除上清液,采用纯水分散,得到单分散的纳米级聚苯乙烯微球;用氢氧化钾或氢氧化钠溶液溶解聚丙烯酸树脂Eudragit得到均相溶液,将该溶液加入到微球的分散液中,搅拌混合均匀,调整混合液的PH值到5.0~6.5,检测微球粒径,确保微球没有聚集,继续搅拌10~12小时,离心处理,去上清液,用水分散得到所述纳米聚苯乙烯微球
2.根据权利要求1所述的制备方法,其特征在于,所述聚丙烯酸树脂Eudragit是聚丙烯酸树脂Eudragit L100-55或L100。
3.一种根据权利要求1所述方法制备的表面包被聚丙烯酸树脂Eudragit的纳米聚苯乙烯微球。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910272776.1A CN109988333B (zh) | 2019-04-04 | 2019-04-04 | 一种聚苯乙烯微球 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910272776.1A CN109988333B (zh) | 2019-04-04 | 2019-04-04 | 一种聚苯乙烯微球 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN109988333A CN109988333A (zh) | 2019-07-09 |
CN109988333B true CN109988333B (zh) | 2023-04-07 |
Family
ID=67132515
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910272776.1A Active CN109988333B (zh) | 2019-04-04 | 2019-04-04 | 一种聚苯乙烯微球 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109988333B (zh) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116626285A (zh) * | 2019-07-19 | 2023-08-22 | 科美博阳诊断技术(上海)有限公司 | 一种均相化学发光分析的方法及其应用 |
CN112240929A (zh) * | 2019-07-19 | 2021-01-19 | 博阳生物科技(上海)有限公司 | 一种用于均相化学发光分析的供体颗粒及其应用 |
CN112240928B (zh) * | 2019-07-19 | 2023-06-13 | 科美博阳诊断技术(上海)有限公司 | 一种均相化学发光分析的方法及其应用 |
CN113125730B (zh) * | 2019-12-31 | 2023-07-07 | 科美博阳诊断技术(上海)有限公司 | 一种白介素6的均相检测试剂盒及其应用 |
CN113125721B (zh) * | 2019-12-31 | 2023-07-07 | 科美博阳诊断技术(上海)有限公司 | 一种肌酸激酶同工酶的均相检测试剂盒及其应用 |
CN113125715B (zh) * | 2019-12-31 | 2023-07-28 | 科美博阳诊断技术(上海)有限公司 | 一种人类免疫缺陷病毒抗体检测试剂盒及其应用 |
CN113125701B (zh) * | 2019-12-31 | 2024-01-30 | 科美博阳诊断技术(上海)有限公司 | 一种均相化学发光检测试剂盒及其应用 |
CN113125712B (zh) * | 2019-12-31 | 2023-06-16 | 科美博阳诊断技术(上海)有限公司 | 一种丙型肝炎病毒抗体的均相化学发光检测试剂盒及应用 |
CN116859041A (zh) * | 2019-12-31 | 2023-10-10 | 科美博阳诊断技术(上海)有限公司 | 一种肌酸激酶同工酶的均相检测试剂盒及其应用 |
CN113125714B (zh) * | 2019-12-31 | 2023-06-16 | 科美博阳诊断技术(上海)有限公司 | 一种人类免疫缺陷病毒抗体检测试剂盒及其应用 |
CN113125732B (zh) * | 2019-12-31 | 2023-08-08 | 科美博阳诊断技术(上海)有限公司 | 一种白介素6的均相检测试剂盒及其应用 |
CN116859057A (zh) * | 2019-12-31 | 2023-10-10 | 科美诊断技术(苏州)有限公司 | 一种肌红蛋白的均相检测试剂盒及其应用 |
CN117805359A (zh) * | 2019-12-31 | 2024-04-02 | 科美诊断技术(苏州)有限公司 | 一种肌红蛋白的均相检测试剂盒及其应用 |
CN116819079A (zh) * | 2019-12-31 | 2023-09-29 | 科美博阳诊断技术(上海)有限公司 | 一种受体试剂及其应用 |
CN113193305A (zh) * | 2021-03-22 | 2021-07-30 | 深圳供电局有限公司 | 阻燃锂离子电池隔膜及其制备方法和应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1487019A (zh) * | 2003-07-31 | 2004-04-07 | 上海交通大学 | 纳米硫化镉/聚苯乙烯核壳微球的制备方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI322793B (en) * | 2006-10-02 | 2010-04-01 | Chung Cheng Inst Of Technology Nat Defense University | Functionalized magnetizable microspheres and preparation thereof |
CN102675501A (zh) * | 2012-06-08 | 2012-09-19 | 上海蓝怡科技有限公司 | 一种粒径可控单分散聚苯乙烯微球的制备方法 |
US11833255B2 (en) * | 2015-10-07 | 2023-12-05 | The Brigham And Women's Hospital, Inc. | Nanoparticles with pH triggered drug release |
CN105949379B (zh) * | 2016-05-18 | 2018-10-02 | 珠海光驭科技有限公司 | 一种纳米微球和表面光学材料以及表面光学材料的制备方法 |
CN108623725A (zh) * | 2017-03-20 | 2018-10-09 | 韩越秦 | 一种小粒径聚苯乙烯纳米微球的制备方法 |
-
2019
- 2019-04-04 CN CN201910272776.1A patent/CN109988333B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1487019A (zh) * | 2003-07-31 | 2004-04-07 | 上海交通大学 | 纳米硫化镉/聚苯乙烯核壳微球的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN109988333A (zh) | 2019-07-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN109988333B (zh) | 一种聚苯乙烯微球 | |
US6573313B2 (en) | Amphiphilic core-shell latexes | |
US5814687A (en) | Magnetic polymer particle and process for manufacturing the same | |
US8703289B2 (en) | Organic polymer particles and process for producing the same, magnetic particles for diagnostics, carboxyl group-containing particles and process for producing the same, and probe-bound particles and process for producing the same | |
CN104031201B (zh) | 一种用于生物蛋白分离的磁性微球的制备方法及其应用 | |
US20090099342A1 (en) | Process for Preparing Composite Particles, Composite Particles Obtained, and Their Use in a Diagnostic Test | |
Abdelrahman et al. | Surface functionalization methods to enhance bioconjugation in metal-labeled polystyrene particles | |
Zgheib et al. | Cerium oxide encapsulation by emulsion polymerization using hydrophilic macroRAFT agents | |
JP4716034B2 (ja) | 磁性粒子およびその製造方法 | |
Niu et al. | Organic–inorganic hybrid nanomaterials prepared via polymerization-induced self-assembly: recent developments and future opportunities | |
CN111944191B (zh) | 一种量子点荧光微球及其制备方法 | |
JP3647466B2 (ja) | 校正単分散磁化性微小球の新規なラテックス、その製法および化学または生物学でのラテックスの用途 | |
CN109939624A (zh) | 一种生物相容性涂层可控的核壳型磁性粒子的制备方法 | |
Generalova et al. | Design of polymer particle dispersions (latexes) in the course of radical heterophase polymerization for biomedical applications | |
CN106565908B (zh) | 一种单分散大粒径聚合物微球的制备方法 | |
JP4548598B2 (ja) | 磁性粒子およびその製造方法、ならびに生化学用担体 | |
JP3743072B2 (ja) | 磁性ポリマー粒子の製造方法 | |
CN101735367A (zh) | 一种纳米磁性聚合物复合微球的制备方法 | |
JP2006226689A (ja) | 免疫検査用磁性粒子 | |
JP2006226690A (ja) | 免疫検査用磁性粒子 | |
CN110283282B (zh) | 一种功能性毛刷状荧光微球的制备方法 | |
WO2011003240A1 (en) | Formulation comprising terpolymer and active substance, and preparation thereof | |
Charreyre et al. | Surface functionalization of polystyrene nanoparticles with liposaccharide monomers: preparation, characterization and applications | |
CN115181215B (zh) | 一种均一粒径免疫微米磁珠的制备方法 | |
JP2003277455A (ja) | ポリマー粒子の製造方法、ポリマー粒子および生理活性物質担体 |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant |