CN102757538A - Intelligent natural polymer-synthetic polymer copolymer microgel and preparation method thereof - Google Patents
Intelligent natural polymer-synthetic polymer copolymer microgel and preparation method thereof Download PDFInfo
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- CN102757538A CN102757538A CN2012101385591A CN201210138559A CN102757538A CN 102757538 A CN102757538 A CN 102757538A CN 2012101385591 A CN2012101385591 A CN 2012101385591A CN 201210138559 A CN201210138559 A CN 201210138559A CN 102757538 A CN102757538 A CN 102757538A
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Abstract
The invention relates to intelligent natural polymer-synthetic polymer copolymer microgel and a preparation method thereof. The microgel is obtained by soap-free emulsion polymerization and is composed of natural polymers and synthetic polymers, wherein the natural polymers are casein, gelatin, bovine serum albumin and other natural amphoteric polyelectrolytes, and the synthetic polymers are alkylated acrylamide polymers with a temperature responsive property. The microgel is responsive to both pH and temperature; and the biomacromolecule portion contained in the microgel has good biocompatibility and biodegradability and the synthetic polymer portion has a temperature responsive property. Therefore, the microgel can be used as a base material of intelligent drug carriers, controlled-release materials and biosensors and has good application prospects in the fields of biomedicine and pharmacy.
Description
Technical field
The present invention relates to a kind of preparation method of intelligent microgel, specifically is a kind of pH of having, temperature dual response multipolymer microgel and preparation method thereof, belongs to functional high molecule material and pharmaceutical necessities technical field.
Background technology
Microgel is a kind of crosslinked micropartical, and its diameter is at 50nm-5 μ m, and internal structure is typical network structure.If comprise the part of water-soluble or water-swellable then can regard it as hydrogel.The environment-responsive microgel is meant when Externality such as temperature, pH value, ionic strength change; Swelling or deswelling behavior take place in microgel inside thereupon; Thereby cause the volume generation swelling or the contraction of microgel, and cause one type of microgel of performance change such as aperture degree, rheological.Past is more to the microgel research of single stimuli responsive; But Along with people's improves constantly material performance requirement; The microgel of single stimuli responsive can not satisfy the application of some special dimensions, and people hope to obtain simultaneously two or more to be stimulated the microgel that produces multiple response.Wherein particularly active with the research of the responsive microgel of pH and temperature dual, because pH and temperature are convenient to the stimulus signal operated easily again, the while also is two important factors in physiology, the biological and chemical system.The double-response microgel that possesses temperature and pH susceptibility has a good application prospect in fields such as biology, medical science, like the carrier of useful as drug molecule, controls the absorption and the release of drug molecule through pH or temperature; Carrier as bioactive molecules both can guarantee the biomolecules non-inactivation, and response speed is faster arranged again.In addition, microgel also can be used for multiple fields such as chemical separation, clinical diagnosis, and therefore, the research that possesses pH and temperature dual response microgel has simultaneously received suitable attention.
It is main monomer that Chinese patent CN1847473A discloses with N-NSC 11448 and vinylformic acid etc.; Exist at linking agent and emulsifying agent; Initiated polymerization prepares the method for the microgel of pH and temperature dual response, but has used emulsifying agent in this method, has increased difficulty for the purifying products in later stage.Cheng Xiangsheng etc. (University Of Qingdao's journal 2010,1,60) have reported that with N-caprolactam and methylacrylic acid be main monomer, adopt precipitation polymerization to prepare the gel copolymer that pH and temperature double-bang firecracker are answered.Li Zhiju etc. (China Synthetic Rubber Industry 2008,1,46) have reported that with N-NSC 11448, AAEM and vinylformic acid be monomer, adopt emulsifier-free emulsion polymerization to prepare the multipolymer microgel of pH and temperature dual response.The preparation method of related microgel is based on synthetic macromolecule in above-mentioned patent or the document, exists the shortcoming of biocompatibility and biological degradability difference.
Summary of the invention
It is a kind of biodegradable and have the graft copolymer microgel of pH, temperature dual response that one of the object of the invention is to provide, and such microgel has better biocompatibility and biological degradability.And the natural polymer subdivision of such microgel is a polyamphoteric electrolyte; In different pH media, have different electric charges; Drug molecule that can be through electrostatic interaction selective adsorption band xenogenesis electric charge, and the selectivity that can carry out medicine through the pH of control agent is uploaded and is discharged.
Two of the object of the invention is to provide a kind of short-cut method for preparing this analog copolymer microgel, and not only polymerization process is simple, can disposablely accomplish, and has avoided the use of emulsifying agent, makes the purifying of product simple and easy to do.
The objective of the invention is to realize through following technical scheme:
By natural biological polymer and alkyl-substituted acrylamide class monomer; In the presence of linking agent; Make through emulsifier-free emulsion polymerization have pH, the graft copolymer microgel of temperature dual response, wherein the quality of natural polymer is 25 parts, the monomeric quality of alkyl-substituted acrylamide class is 25～150 parts; The quality of linking agent is 0.25～7.5 part, and the quality of initiator is 0.001～0.003 part.
In the such scheme, the preparation technology of described microgel is following technology: with natural polymer and Na
2CO
3(or K
2CO
3) be dissolved in the deionized water, to dissolving fully, the pH of system is reached between 10.0～12.0 50 ℃ of stirred in water bath, add alkyl-substituted acrylamide class monomer and linking agent, be warming up to 60～85 ℃, logical N
2Gas 30min adds initiator, at N
2Gas shiled is reaction 2～4h down, then obtains the graft copolymer microgel.The product that obtains is fully dialysed with zero(ppm) water after (dialysis tubing, molecular weight cut-off are 10000), carries out lyophilize then, then obtains the multipolymer microgel of title product casein graft N-NSC 11448.
Initiator described in the above-mentioned technology is the alkyl peroxide initiator, like one or more the mixture in tertbutyl peroxide, the cumene hydroperoxide hydrogen etc.
The pH that the present invention relates to, temperature dual response graft copolymer microgel are made up of the alkyl-substituted acrylamide polymkeric substance of natural biological polymer and temperature-responsive; Not only have pH, temperature dual responsiveness; And have good biocompatibility and biological degradability, and its preparation method is simple, and cost is low; Therefore, this base polymer has very big application potential at aspects such as the transmission of medicine/DNA/ enzyme, medicament slow release material, biosensor, intelligent coating.
Embodiment
Embodiment one:
Having stirring, reflux condensing tube, TM and N
2In the four-hole bottle of airway, add 0.25g casein, 0.1gNa
2CO
3With the 50g deionized water, at 50 ℃ of stirred in water bath 30min, add 1gN-NSC 11448 and 0.01g polyethyleneglycol diacrylate then, stir 15min, be warmed up to 80 ℃, logical N
230min adds initiator TBHP7.2x10
-4G (0.8mL10mmol/L), N
2Protection is reaction 2h down.The product that obtains is fully dialysed with zero(ppm) water after (dialysis tubing, molecular weight cut-off are 10000), carries out lyophilize then, then obtains the multipolymer microgel of title product casein graft N-NSC 11448.It is the two response type microgels of pH and temperature of low crosslinking degree, and swelling ratio pH value hour is 4.6, and response temperature is 32 ℃.
Embodiment two:
Having stirring, reflux condensing tube, TM and N
2In the four-hole bottle of airway, add 0.25g casein, 0.1g Na
2CO
3With the 50g deionized water, stir 30min at 50 ℃, add 1gN-isopropyl methyl acrylic amide and 0.01gN then, the N-methylene-bisacrylamide stirs 15min, is warmed up to 80 ℃, logical N
230min adds initiator TBHP7.2x10
-4G (0.8mL10mmol/L), N
2Protection is reaction 2h down.The product that obtains is fully dialysed with zero(ppm) water after (dialysis tubing, molecular weight cut-off are 10000), carries out lyophilize then, then obtains the multipolymer microgel of title product casein graft N-NSC 11448.It is the two response type microgels of pH and temperature of low crosslinking degree, and swelling ratio pH value hour is 4.6, and response temperature is 32 ℃.
Embodiment three:
Having stirring, reflux condensing tube, TM and N
2In the four-hole bottle of airway, add 0.25g gelatin, 0.1g Na
2CO
3With the 50g deionized water, stir 30min at 50 ℃, add 1gN then, N-diethylammonium acrylic amide and 0.03gN, the N-methylene-bisacrylamide stirs 15min, is warmed up to 80 ℃, logical N
230min adds initiator TBHP7.2x10
-4G (0.8mL10mmol/L), N
2Protection is reaction 2h down.The product that obtains is fully dialysed with zero(ppm) water after (dialysis tubing, molecular weight cut-off are 10000), carries out lyophilize then, then obtains the multipolymer microgel of title product gelatin graft N-NSC 11448.It is the two response type microgels of pH and temperature of medium degree of crosslinking, and swelling ratio pH value hour is 4.8, and response temperature is 32 ℃.
Embodiment four:
Having stirring, reflux condensing tube, TM and N
2In the four-hole bottle of airway, add 0.25g gelatin, 0.2gNa
2CO
3With the 50g deionized water, stir 30min at 50 ℃, add 1.5g N-ethyl-methyl acrylic amide and 0.075gN then, the N-methylene-bisacrylamide stirs 15min, is warmed up to 80 ℃, logical N
230min adds initiator TBHP7.2x10
-4G (0.8mL 10mmol/L), N
2Protection is reaction 2h down.The product that obtains is fully dialysed with zero(ppm) water after (dialysis tubing, molecular weight cut-off are 10000), carries out lyophilize then, then obtains the multipolymer microgel of title product gelatin graft N-NSC 11448.It is the two response type microgels of pH and temperature of high-crosslinking-degree, and swelling ratio pH hour is 4.8, and response temperature is 32 ℃.
Embodiment five:
Having stirring, reflux condensing tube, TM and N
2In the four-hole bottle of airway, add 0.25g bovine serum albumin, 0.1g Na
2CO
3With the 48.2g deionized water, stir 30min at 50 ℃, add 1.25g N-ethyl acrylamide and 0.045gN then, the N-methylene-bisacrylamide stirs 15min, is warmed up to 80 ℃, logical N
230min adds initiator TBHP7.2x10
-4G (0.8mL 10mmol/L), N
2Protection is reaction 2h down.The product that obtains is fully dialysed with zero(ppm) water after (dialysis tubing, molecular weight cut-off are 10000), carries out lyophilize then, then obtains the multipolymer microgel of title product bovine serum albumin graft N-NSC 11448.It is the two response type microgels of pH and temperature of medium degree of crosslinking, and swelling ratio pH value hour is 4.7, and response temperature is 32 ℃.
Embodiment six
Having stirring, reflux condensing tube, TM and N
2In the four-hole bottle of airway, add 0.25g bovine serum albumin, 0.1g Na
2CO
3With the 48.2g deionized water, stir 30min at 50 ℃, add 1.5g N-cyclopropyl acrylic amide and 0.075g polyethylene glycol dimethacrylate then, stir 15min, be warmed up to 80 ℃, logical N
230min adds initiator TBHP7.2x10
-4G (0.8mL 10mmol/L), N
2Protection is reaction 2h down.The product that obtains is fully dialysed with zero(ppm) water after (dialysis tubing, molecular weight cut-off are 10000), carries out lyophilize then, then obtains the multipolymer microgel of title product bovine serum albumin graft N-NSC 11448.It is the two response type microgels of pH and temperature of high-crosslinking-degree, and swelling ratio pH hour is 4.7, and response temperature is 32 ℃.
Claims (4)
1. the preparation method of a pH, temperature dual response microgel, it is characterized in that: such microgel is to be obtained through emulsifier-free emulsion polymerization under the situation that linking agent exists by natural polymer, alkyl-substituted acrylamide class monomer; Wherein the quality of natural polymer is 25 parts, and the monomeric quality of alkyl-substituted acrylamide class is 25～150 parts, and the quality of linking agent is 0.25～7.5 part, and the quality of initiator is 0.001～0.003 part.
2. preparation method according to claim 1 is characterized in that emulsifier-free emulsion polymerization technology is following technology: with natural polymer and Na
2CO
3(or K
2CO
3) be dissolved in the deionized water, to dissolving fully, the pH of system is reached between 10.0～12.0 50 ℃ of stirred in water bath, add alkyl-substituted acrylamide class monomer and linking agent, be warming up to 60～85 ℃, logical N
2Gas 30min adds initiator, at N
2Gas shiled is reaction 2～4h down, then obtains the graft copolymer microgel; The product that obtains is fully dialysed with zero(ppm) water after (dialysis tubing, molecular weight cut-off are 10000), carries out lyophilize then, then obtains the multipolymer microgel of title product casein graft N-NSC 11448.
3. preparation method according to claim 1 and 2 is characterized in that natural polymer subdivision in such microgel is one or more the mixture in casein with good biocompatibility, biological degradability, gelatin, these natural amphoteric polyelectrolytes of bovine serum albumin; Synthetic macromolecule partly has temperature-responsive; Be to get through polyreaction; Used monomer is N, the mixture of one or more in N-diethylammonium acrylic amide, N-NSC 11448, N-isopropyl methyl acrylic amide, N-cyclopropyl acrylic amide, N-ethyl acrylamide, the N-ethyl-methyl acrylic amide; Used linking agent is N, N '-methylene-bisacrylamide, N, N '-eight methylene-bisacrylamide, N, the mixture of one or more in N '-dodecyl methylene-bisacrylamide, the above water-soluble cross-linker of polyethylene glycol dimethacrylate; The used initiator of emulsifier-free emulsion polymerization is the alkyl peroxide initiator.
4. preparation method according to claim 3 is characterized in that said alkyl peroxide initiator is one or more the mixture in tertbutyl peroxide, the cumene hydroperoxide hydrogen.
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| CN103495177A (en) * | 2013-09-27 | 2014-01-08 | 西北师范大学 | Preparation of albumin compound thermo-sensitive macromolecule micro-capsule and application thereof as drug carrier |
| CN106619491A (en) * | 2017-01-24 | 2017-05-10 | 泉州亚林新材料科技有限公司 | Drug sustained-release hydrogel and preparation method thereof |
| CN109385137A (en) * | 2018-11-27 | 2019-02-26 | 常州大学 | A kind of water-borne UV-curing ink and preparation method thereof that reactive and Temperature-Sensitive Microgel is modified |
| CN109513038A (en) * | 2018-12-14 | 2019-03-26 | 华南理工大学 | The temperature-sensitive hydrogel and preparation method thereof of supported copper metal organic framework nanoparticle |
| CN110558968A (en) * | 2019-09-05 | 2019-12-13 | 中国科学院长春应用化学研究所 | microgel wearable sensor and preparation method thereof |
| CN112244010A (en) * | 2020-10-26 | 2021-01-22 | 中国农业科学院农业环境与可持续发展研究所 | Temperature response type nanogel, preparation method thereof and preparation method of temperature response type pesticide drug-loading system containing nanogel |
| WO2021238577A1 (en) * | 2020-05-29 | 2021-12-02 | 深圳硅基传感科技有限公司 | Polymer film for biosensor and preparation method therefor |
| CN115948013A (en) * | 2022-09-01 | 2023-04-11 | 浙江省医疗器械检验研究院(国家食品药品监督管理局杭州医疗器械质量监督检验中心) | Quick-gelling hydrogel and preparation method and application thereof |
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2012
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| CN103495177A (en) * | 2013-09-27 | 2014-01-08 | 西北师范大学 | Preparation of albumin compound thermo-sensitive macromolecule micro-capsule and application thereof as drug carrier |
| CN106619491A (en) * | 2017-01-24 | 2017-05-10 | 泉州亚林新材料科技有限公司 | Drug sustained-release hydrogel and preparation method thereof |
| CN106619491B (en) * | 2017-01-24 | 2019-04-30 | 泉州亚林新材料科技有限公司 | A kind of medicament slow release hydrogel and preparation method thereof |
| CN109385137A (en) * | 2018-11-27 | 2019-02-26 | 常州大学 | A kind of water-borne UV-curing ink and preparation method thereof that reactive and Temperature-Sensitive Microgel is modified |
| CN109385137B (en) * | 2018-11-27 | 2022-01-25 | 常州大学 | Reactive and temperature-sensitive microgel modified aqueous UV curing ink and preparation method thereof |
| CN109513038A (en) * | 2018-12-14 | 2019-03-26 | 华南理工大学 | The temperature-sensitive hydrogel and preparation method thereof of supported copper metal organic framework nanoparticle |
| CN110558968A (en) * | 2019-09-05 | 2019-12-13 | 中国科学院长春应用化学研究所 | microgel wearable sensor and preparation method thereof |
| WO2021238577A1 (en) * | 2020-05-29 | 2021-12-02 | 深圳硅基传感科技有限公司 | Polymer film for biosensor and preparation method therefor |
| CN112244010A (en) * | 2020-10-26 | 2021-01-22 | 中国农业科学院农业环境与可持续发展研究所 | Temperature response type nanogel, preparation method thereof and preparation method of temperature response type pesticide drug-loading system containing nanogel |
| CN115948013A (en) * | 2022-09-01 | 2023-04-11 | 浙江省医疗器械检验研究院(国家食品药品监督管理局杭州医疗器械质量监督检验中心) | Quick-gelling hydrogel and preparation method and application thereof |
| CN115948013B (en) * | 2022-09-01 | 2023-11-14 | 浙江省医疗器械检验研究院(国家食品药品监督管理局杭州医疗器械质量监督检验中心) | Quick glue gel and preparation method and application thereof |
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Application publication date: 20121031 |