WO2018000423A1 - 温敏性纳米胶囊及其制备方法 - Google Patents

温敏性纳米胶囊及其制备方法 Download PDF

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WO2018000423A1
WO2018000423A1 PCT/CN2016/088133 CN2016088133W WO2018000423A1 WO 2018000423 A1 WO2018000423 A1 WO 2018000423A1 CN 2016088133 W CN2016088133 W CN 2016088133W WO 2018000423 A1 WO2018000423 A1 WO 2018000423A1
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Prior art keywords
temperature
parts
sensitive
nanocapsule
preparing
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PCT/CN2016/088133
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English (en)
French (fr)
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鲁希华
赵迪
王丽英
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安徽美科迪智能微胶囊科技有限公司
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Application filed by 安徽美科迪智能微胶囊科技有限公司 filed Critical 安徽美科迪智能微胶囊科技有限公司
Priority to ES16906822T priority Critical patent/ES2871857T3/es
Priority to EP16906822.8A priority patent/EP3479820B1/en
Priority to US16/313,909 priority patent/US10543471B2/en
Publication of WO2018000423A1 publication Critical patent/WO2018000423A1/zh

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    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
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    • C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
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Definitions

  • the invention belongs to the technical field of nanocapsules and preparation thereof, and relates to a temperature sensitive nanocapsule and a preparation method thereof.
  • the microcapsules have a particle size of between 1 and 1000 ⁇ m.
  • the prepared microcapsules can have a particle size of ⁇ 1 ⁇ m, between 1 and 1000 nm, and the particle size is in the nanometer.
  • the range of microcapsules is called nanocapsules.
  • nanocapsules Compared with traditional microcapsules, nanocapsules have the advantages of: (1) facilitating further surface modification of materials, increasing embedding rate, changing distribution state and targeting; (2) nano microcapsules have good stability and are easy to process.
  • Nanocapsules have good biocompatibility and low toxic and side effects; (4) can be made into sustained release granules to prolong the efficacy of the drug; (5) can prevent the destruction of other components of the food.
  • Nanocapsule technology has been internationally listed as a high-tech research and development in the 21st century. Nanocapsules have been used in food condiments, agriculture and biotechnology, biomedicine, and cosmetics and textiles.
  • nanocapsules such as the use of miniemulsion polymerization in the Polymerization mechanism of poly(ethylene glycol dimethacrylate)fragranate nanocapsules, but it is not temperature sensitive; Preparation and characteristics of nanocapsules containing essential oil for textile application
  • the perfume nanocapsules were prepared by emulsion polymerization, but the embedding rate was only 85.4%; the synthesis of fragrance/silica nanocapsules through a sol-gel process in miniemulsions and their application as undergo finishing agents was prepared by sol-gel method but its nanocapsules were prepared.
  • the reaction system has certain toxicity; the fragrance is prepared by using nanoprecipitated hair in Novel biocompatible nanocapsules for slow release of fragrances on the human skin, but its release is not temperature sensitive. Therefore, it has not been reported to prepare a nanocapsule with good biocompatibility wall material, high embedding rate and controlled release.
  • the invention adopts a green environmental protection system, and the preparation method is simple and mild, and the obtained nano-capsule is non-toxic, has high embedding rate and temperature sensitivity, can control and release the core material, and has wide fields in medicine, daily chemical, textiles and the like. Application prospects.
  • the technical problem to be solved by the present invention is to provide a temperature sensitive nanocapsule and a preparation method thereof, which are used
  • the reactive monomer is two different N-alkyl acrylamide monomers, the two monomers have good biocompatibility, and the crosslinking agent is ethylene glycol dimethacrylate and dimethacrylic acid 1,4 One or more of -butylene glycol ester and 1,6-hexanediol dimethacrylate, the cross-linking agent is non-toxic and environmentally friendly, and contains two double bonds, which can be polymerized to form a long-chain polymer.
  • the first two monomers are crosslinked to form a high-density three-dimensional network polymer to embed the core material.
  • the polymer used in the nanocapsule wall material synthesized in the invention is non-toxic and environmentally friendly.
  • the technical solution adopted by the present invention includes:
  • the method for preparing the temperature sensitive nanocapsules comprises the following steps: using two different N-alkyl acrylamide monomers to form a wall material by free radical polymerization to obtain a temperature sensitive nanocapsule;
  • the preparation steps are:
  • the structural formula of the N-alkyl acrylamide monomer is:
  • R 2 is Or —H
  • the structural formula of the crosslinking agent is:
  • R 2 is Or —H
  • R 3 is Or —H
  • R 4 is Or —H
  • the core material is at least one of an ultraviolet absorber, a flavor and fragrance, a phase change material, and a medicine; and the ultraviolet absorber is octocrylene or benzophenone.
  • phase change material is paraffin or n-tetradecane or n-pentadecane or n-hexadecane or n-heptadecane or n-octadecane or n-nonadecane or n-icosane or n-docosane or n- Dioxane or n-docosane or n-tetracosane;
  • the drug is a vitamin oil or an anti-tumor drug.
  • the components are: by weight:
  • the introduction of nitrogen means that the nitrogen gas is continuously protected after the formation of the nanoemulsion until the end of the reaction; the reaction time is from 3 h to 4 h.
  • a temperature sensitive nanocapsule prepared by the preparation method as described above, wherein the temperature sensitive nanocapsule is embedded in a polymer wall layer, wherein the polymer wall layer is composed of an oil phase
  • the monomer undergoes radical polymerization at the water-oil interface to form a polymer wall layer; the embedding rate of the temperature-sensitive nanocapsule is 90% to 94%, and the formed nanocapsule particle size PDI is 0.09 to 0.17 and the particle The diameter is ⁇ 150 nm.
  • the invention uses two different N-alkyl acrylamide monomers to radically polymerize to form a wall material of a novel nanocapsule, and uses ultraviolet absorber, flavor and fragrance, phase change material and one or more materials in medicine as a core material, and utilizes Nanocapsules were prepared by miniemulsion polymerization.
  • the aqueous phase is an aqueous solution of a water-soluble emulsifier
  • the oil phase is a mixture of a core material, two different N-alkyl acrylamide monomers, a crosslinking agent, an initiator, and a co-stabilizer.
  • the microemulsion is formed by high-speed shearing, and the nanoemulsion is formed by ultrasonication.
  • the initiator initiates radical polymerization of the monomer in the oil phase to form a polymer wall layer, and the core material is embedded therein.
  • miniemulsion polymerization is defined as follows: a stable emulsion dispersion system composed of submicron droplets (50-500 nm) is called a miniemulsion, and the corresponding droplet nucleation polymerization method is called miniemulsion polymerization.
  • the monomer forms stable, uniformly dispersed submicron droplets, which greatly increase the surface area compared to the macromonomer droplets of the conventional emulsion, making most of the
  • the emulsifiers are adsorbed to the surface of these droplets, so that there is not enough free emulsifier in the aqueous phase to form micelles or stable homogeneous nucleation, at which point the droplets become the main site of nucleation. It not only retains most of the advantages and unique features of traditional emulsion polymerization, but also expands the application range of emulsion polymerization.
  • the monomers used in the present invention can undergo cross-linking as a reactive monomer due to their structural characteristics, and their structures They are as follows:
  • the present invention uses two different N-alkyl acrylamides as monomers, and the monomer has good biocompatibility and is itself non-toxic, so there is no unreacted toxic monomer residue remaining after the reaction. base;
  • the wall material synthesized by the invention is non-toxic and has good temperature sensitivity, so that the microcapsules can be well applied to products related to human body;
  • the emulsifier used in the invention is non-toxic and environmentally friendly, and does not introduce any toxic substances into the reaction system, so that the invention system is green and environmentally friendly;
  • the initiator used in the present invention can be decomposed at a low temperature to generate a primary radical to activate a radical polymerization of a wall-forming monomer. Not only can it effectively and completely trigger the reaction, but it also greatly reduces energy consumption;
  • the method used in the present invention is a miniemulsion polymerization method, which nucleates submicron droplets, and at a certain temperature and under N 2 environment, the initiator initiates radical polymerization of monomers in the oil phase at the water-oil interface.
  • a polymer wall layer the core material is embedded therein; the formed wall material is completely covered on the surface of the core material, and the encapsulation rate of the core material is high, and the formed nanocapsule has a uniform particle size of less than 150 nm;
  • the nanocapsules and preparation process are all green and environmentally friendly.
  • the prepared nanocapsules are harmless to the human body and have broad application prospects in industries such as flavors and fragrances, biomedicine, daily cosmetics and textile nanocapsules.
  • 1 is a schematic diagram showing the mechanism of radical polymerization of monomers in an oil phase to form a polymer wall layer by nucleating submicron droplets in a certain temperature and under N 2 atmosphere;
  • Figure 3 is a particle size distribution diagram of the nanocapsule
  • Figure 4 is a graph showing the temperature sensitivity of nanocapsules.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • the prepared temperature-sensitive nanocapsules are embedded in the core material.
  • the monomers in the oil phase undergo radical polymerization at the water-oil interface to form a polymer wall layer.
  • the basic properties of the temperature-sensitive nanocapsules are shown in the following table.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • the prepared temperature-sensitive nano-capsule is a core material embedded in the oil phase to generate free radicals at the water-oil interface.
  • the basic properties of the temperature sensitive nanocapsules are shown in the following table by polymerization to form a polymer wall layer.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • the aqueous phase was added to the oil phase, and the microemulsion was formed by shearing at a shear rate of 7000 rpm for 5 minutes.
  • the nanoemulsion is formed by ultrasonication at 50% amplitude for 15 min;
  • the parts by weight of N,N-diethylacrylamide are 14 parts, 12 parts, 10 parts, 8 parts and 6 parts, respectively, the parts by weight of N,N-dimethyl acrylamide are 6 parts, 8 respectively.
  • the prepared temperature-sensitive nanocapsules are formed by embedding water lotus essence in a radical polymerization of a monomer in an oil phase at a water-oil interface to form a high polymer.
  • the temperature sensitivity of the temperature sensitive nanocapsules is shown in Figure 4. The relevant data and other performance results are shown in the following table.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • the prepared temperature-sensitive nanocapsules are formed by embedding floral essence in a polymer wall layer formed by radical polymerization of monomers in the oil phase at the water-oil interface, and the microcapsules are displayed under transmission electron microscope. It is spherical, has obvious core-shell structure, good dispersibility, and no aggregated large particles. As shown in Fig. 2, the embedding rate of the temperature sensitive nanocapsule is 93%, and the formed nanocapsule particle size PDI is 0.1. The particle size is 140 to 149 nm, as shown in FIG.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding paraffin wax in a polymer wall layer formed by radical polymerization of monomers in the oil phase at the water-oil interface, and having a temperature-sensitive nanocapsule package.
  • the burying rate was 94%, and the formed nanocapsules had a particle diameter PDI of 0.15 and a particle diameter of 110 to 130 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding n-tetradecane in a polymer wall layer formed by radical polymerization of monomers in the oil phase at the water-oil interface, and having temperature-sensitive nano-layers.
  • the embedding rate of the capsule was 94%, and the formed nanocapsule had a particle diameter PDI of 0.15 and a particle diameter of 130 to 149 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding n-pentadecane in a polymer wall layer formed by radical polymerization of monomers in the oil phase at the water-oil interface, and having temperature-sensitive nano-particles.
  • the embedding rate of the capsule was 91%, and the formed nanocapsule had a particle diameter PDI of 0.11 and a particle diameter of 110 to 130 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding n-hexadecane in a polymer wall layer formed by radical polymerization of monomers in the oil phase at the water-oil interface, and having temperature-sensitive nano-capsules.
  • the embedding rate of the capsule was 92%, and the formed nanocapsule had a particle diameter PDI of 0.11 and a particle diameter of 110 to 130 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding n-heptadecane in a polymer wall layer formed by free radical polymerization of monomers in the oil phase at the water-oil interface, and having temperature-sensitive nano-particles.
  • the embedding rate of the capsule was 93%, and the formed nanocapsule had a particle diameter PDI of 0.12 and a particle diameter of 110 to 130 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding n-octadecane in a polymer wall layer formed by free radical polymerization of monomers in the oil phase at the water-oil interface, and having temperature-sensitive nano-capsules.
  • the embedding rate of the capsule was 94%, and the formed nanocapsule had a particle diameter PDI of 0.12 and a particle diameter of 110 to 130 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • the test shows that the prepared temperature-sensitive nanocapsules are formed by embedding n-nonadecane in a polymer wall layer formed by radical polymerization of a monomer in the oil phase at the water-oil interface, and having temperature-sensitive nano-particles.
  • the embedding rate of the capsule was 90%, and the formed nanocapsule had a particle diameter PDI of 0.13 and a particle diameter of 110 to 130 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding n-icosane in a polymer wall layer formed by radical polymerization of monomers in the oil phase at the water-oil interface, and having temperature-sensitive nano-capsules.
  • the embedding rate of the capsule was 90%, and the formed nanocapsule had a particle diameter PDI of 0.13 and a particle diameter of 110 to 130 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding n-docosane in a polymer wall layer formed by radical polymerization of monomers in the oil phase at the water-oil interface, and have temperature sensitivity.
  • the encapsulation efficiency of the nanocapsules was 91%, and the formed nanocapsules had a particle diameter PDI of 0.14 and a particle diameter of 110 to 130 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding n-docosane in a polymer wall layer formed by radical polymerization of monomers in the oil phase at the water-oil interface, and have temperature sensitivity.
  • the encapsulation efficiency of the nanocapsules was 91%, and the formed nanocapsules had a particle diameter PDI of 0.14 and a particle diameter of 90 to 110 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding n-tricosane in a polymer wall layer formed by radical polymerization of monomers in the oil phase at the water-oil interface, and have temperature sensitivity.
  • the encapsulation efficiency of the nanocapsules was 92%, and the formed nanocapsules had a particle diameter PDI of 0.15 and a particle diameter of 90 to 110 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding n-tetracosane in a polymer wall layer formed by radical polymerization of monomers in the oil phase at the water-oil interface, and have temperature sensitivity.
  • the encapsulation efficiency of the nanocapsules was 92%, and the formed nanocapsules had a particle diameter PDI of 0.15 and a particle diameter of 90 to 110 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • the test shows that the prepared temperature-sensitive nanocapsules are formed by embedding vitamin oil in a polymer wall layer formed by radical polymerization of monomers in the oil phase at the water-oil interface, and having temperature-sensitive nanocapsules.
  • the embedding rate was 93%, and the formed nanocapsules had a particle diameter PDI of 0.15 and a particle diameter of 90 to 110 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • the test shows that the prepared temperature-sensitive nanocapsules are formed by embedding anti-tumor drugs in a polymer wall layer formed by radical polymerization of monomers in the oil phase at the water-oil interface, and having temperature-sensitive nanocapsules.
  • the embedding rate was 93%, and the formed nanocapsule had a PDI of 0.16 and a particle diameter of 90 to 110 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding a core material in a polymer wall layer formed by radical polymerization of a monomer in an oil phase at a water-oil interface, and having a temperature-sensitive nanocapsule.
  • the embedding rate was 94%, and the formed nanocapsule had a particle diameter PDI of 0.16 and a particle diameter of 90 to 110 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding a core material in a polymer wall layer formed by radical polymerization of a monomer in an oil phase at a water-oil interface, and having a temperature-sensitive nanocapsule.
  • the embedding rate was 94%, and the formed nanocapsule had a PDI of 0.17 and a particle diameter of 90 to 110 nm.
  • a preparation method of temperature-sensitive nanocapsules the preparation steps are as follows:
  • Tests show that the prepared temperature-sensitive nanocapsules are formed by embedding a core material in a polymer wall layer formed by radical polymerization of a monomer in an oil phase at a water-oil interface, and having a temperature-sensitive nanocapsule.
  • the embedding rate was 94%, and the formed nanocapsule had a PDI of 0.17 and a particle diameter of 90 to 110 nm.

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Abstract

一种温敏性纳米胶囊，包括芯材和壁材。制备方法包括：首先分别制备水相和油相，混合后高速剪切形成微乳液，经超声或高压均质作用形成纳米乳液；再向乳液中通入氮气，然后在40-80℃的条件下反应3h～4h，整个过程保持在氮气环境中进行，即得。

Description

温敏性纳米胶囊及其制备方法 技术领域
本发明属纳米胶囊及其制备技术领域，涉及温敏性纳米胶囊及其制备方法。
背景技术
一般微胶囊粒径在1～1000μm之间，随着微胶囊技术的不断进步和纳米技术的不断发展，制备的微胶囊粒径能够<1μm，在1～1000nm之间，这种粒径在纳米范围的微胶囊称为纳米胶囊。与传统的微胶囊相比，纳米胶囊的优越性在于：(1)便于材料进一步表面修饰、提高包埋率、改变分布状态和靶向性；(2)纳米微胶囊成品稳定性好，便于加工应用和储藏运输；(3)纳米胶囊生物相容性好，毒副作用小；(4)可制成缓释颗粒，延长药物疗效；(5)能够防止食品的其他组分的破坏。纳米胶囊技术已被国际上列为21世纪重点研究开发的高新技术，纳米胶囊已经被应用于食品调味品、农业及生物技术、生物医药、以及化妆品和纺织品等领域。
有关纳米胶囊的制备的报道很多，如Polymerization mechanism of poly(ethylene glycol dimethacrylate)fragrance nanocapsules中采用细乳液聚合法包覆香精但其不具备温敏性；Preparation and characteristics of nanocapsules containing essential oil for textile application中采用乳液聚合法制备香精纳米胶囊但其包埋率仅为85.4％；Synthesis of fragrance/silica nanocapsules through a sol-gel process in miniemulsions and their application as aromatic finishing agents中采用溶胶凝胶法制备纳米胶囊但其反应体系具有一定的毒性；Novel biocompatible nanocapsules for slow release of fragrances on the human skin中采用纳米沉淀发制备香精胶囊但其释放不具有温敏性。因此关于制备出具有良好的生物相容性壁材，高包埋率且具有控制释放纳米胶囊还未见报道。本发明采用绿色环保体系，制备方法简单温和，得到的纳米胶囊无毒，包埋率较高且具有温敏性，可对芯材进行控制缓释，在医药、日化、纺织品等领域有广泛的应用前景。
发明内容
本发明所要解决的技术问题是提供温敏性纳米胶囊及其制备方法，所使用的 反应单体是两种不同的N-烷基丙烯酰胺单体，该两种单体具有良好的生物相容性，交联剂为二甲基丙烯酸乙二醇酯、二甲基丙烯酸1,4-丁二醇酯和二甲基丙烯酸1,6-己二醇酯中的一种及以上，该交联剂无毒绿色环保，并含有两个双键，能在聚合形成高分子长链的同时与前两种单体发生交联，形成高密度三维网状高聚物从而包埋芯材。该发明中合成的纳米胶囊壁材使用的高聚物无毒环保。
为实现上述目的，本发明采用的技术方案包括：
温敏性纳米胶囊的制备方法，采用两种不同的N-烷基丙烯酰胺单体进行自由基聚合形成壁材，制得温敏性纳米胶囊；
制备步骤为：
(1)配制乳化剂水溶液：将乳化剂和去离子水混合，得到水相；
(2)将芯材、两种不同的N-烷基丙烯酰胺单体、交联剂、引发剂和共稳定剂混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，剪切形成微乳液，再或高压均质形成纳米乳液；
(4)向所述纳米乳液通入氮气，40-80℃反应，得到温敏性纳米胶囊；
其中N-烷基丙烯酰胺单体的结构通式为：
Figure PCTCN2016088133-appb-000001
R1为
Figure PCTCN2016088133-appb-000002
R2为
Figure PCTCN2016088133-appb-000003
或—H；
m1＝2,3,4…；m2＝1,2,3,4…；
Figure PCTCN2016088133-appb-000004
其中交联剂的结构通式为：
R1为
Figure PCTCN2016088133-appb-000005
R2为
Figure PCTCN2016088133-appb-000006
或—H；
R3为
Figure PCTCN2016088133-appb-000007
或—H；
R4为
Figure PCTCN2016088133-appb-000008
或—H；
n1＝2,3,4…；n2＝1,2,3,4…；n3＝2,3,4…；n4＝1,2,3,4…；
n5＝2,3,4…；n6＝1,2,3,4…；n7＝2,3,4…；n8＝1,2,3,4…。
作为优选的技术方案：
如上所述的温敏性纳米胶囊的制备方法，所述乳化剂为十二烷基磺酸钠、阿拉伯树胶或聚乙烯醇(水解度为80～90％)。
如上所述的温敏性纳米胶囊的制备方法，所述芯材为紫外吸收剂、香精香料、相变材料和医药中的至少一种；所述紫外吸收剂为奥克立林或二苯酮－3或水杨酸辛酯或巴松1789或甲氧基肉桂酸异辛酯；所述香精香料为薄荷素油或玫瑰香精或柠檬香精或薰衣草香精或绿茶香精或水清莲花香精或花香香精；所述相变材料为石蜡或正十四烷或正十五烷或正十六烷或正十七烷或正十八烷或正十九烷或正二十烷或正二十一烷或正二十二烷或正二十三烷或正二十四烷；所述医药为维生素油或抗肿瘤药物。
如上所述的温敏性纳米胶囊的制备方法，所述单体为N,N-二乙基丙烯酰胺或N,N-二甲基丙烯酰胺或N-异丙基丙烯酰胺或N-乙基丙烯酰胺或N-叔丁基丙烯酰胺或N-正丙基丙烯酰胺或N-甲基,N-乙基丙烯酰胺。
如上所述的温敏性纳米胶囊的制备方法，所述交联剂为二甲基丙烯酸乙二醇酯、二甲基丙烯酸1,4-丁二醇酯和二甲基丙烯酸1,6-己二醇酯中的至少一种。
如上所述的温敏性纳米胶囊的制备方法，所述引发剂为偶氮二异丁腈或过氧化苯甲酰；所述共稳定剂为十六烷或十六醇或十八烷基硫醇。
如上所述的温敏性纳米胶囊的制备方法，所述水相和油相中，按重量份数计，各组分为：
Figure PCTCN2016088133-appb-000009
Figure PCTCN2016088133-appb-000010
如上所述的温敏性纳米胶囊的制备方法，所述剪切的剪切速率为6000～10000rpm，剪切时间为3～6min；所述超声的振幅为50％，超声时间为10～30min。
如上所述的温敏性纳米胶囊的制备方法，所述通入氮气是指在形成纳米乳液之后持续通入氮气保护至反应结束；所述反应的时间为3h～4h。
采用如上所述的制备方法制得的温敏性纳米胶囊，所述温敏性纳米胶囊为将芯材包埋在高聚物壁层中，所述高聚物壁层为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层；所述具有温敏性纳米胶囊的包埋率为90％～94％，形成的纳米胶囊粒径PDI为0.09～0.17且粒径<150nm。
本发明以两种不同的N-烷基丙烯酰胺单体自由基聚合形成新型纳米胶囊的壁材，以紫外吸收剂、香精香料、相变材料和医药中的一种以上材料作为芯材，利用细乳液聚合法制备纳米胶囊。其中，水相是水溶性乳化剂的水溶液，油相是芯材、两种不同的N-烷基丙烯酰胺单体、交联剂、引发剂和共稳定剂的混合物。水相和油相混合后经高速剪切形成微乳液又经过超声作用形成纳米乳液。随后，在一定温度及N2环境下，引发剂引发油相中的单体发生自由基聚合形成高聚物壁层，将芯材包埋其中。
所应用的细乳液聚合原理如下：
细乳液聚合定义如下：以亚微米液滴(50-500nm)构成稳定的乳液分散体系称为细乳液，相应的液滴成核的聚合方式称为细乳液聚合。在细乳液体系中，由于乳化剂和共稳定剂的共同作用，单体形成稳定的、分散均匀的亚微米液滴，与传统乳液的大单体液滴相比，其表面积大大增加，使得大部分乳化剂都吸附到这些液滴表面，致使水相中没有足够的游离乳化剂形成胶束或稳定均相成核，此时液滴成为成核的主要场所。其既保留了传统乳液聚合的大部分优点又具有独特的特点，拓展了乳液聚合的应用范围。
本发明使用的单体如N,N-二乙基丙烯酰胺和N,N-二甲基丙烯酰胺，由于其本身的结构特点，在作为反应单体的同时，能发生交联作用，其结构分别如下所示：
Figure PCTCN2016088133-appb-000011
有益效果
(1)本发明以两种不同的N-烷基丙烯酰胺为单体，该单体具有良好的生物相容性，本身无毒，故不存在反应后留下未反应完的有毒单体残基；
(2)本发明合成的壁材属于无毒且具有良好的温敏性，使得这类微胶囊能很好的应用于和人体相关的产品中；
(3)本发明使用的乳化剂无毒环保，不会给反应体系引入任何有毒的物质，使得该发明体系绿色环保；
(4)本发明所使用的引发剂在低温下便能分解产生初级自由基而激活成壁单体自由基聚合反应。不仅能有效完全地引发反应的进行，而且也大大降低了能源的消耗；
(5)本发明所采用的方法是细乳液聚合法，以亚微米液滴成核，在一定温度及N2环境下，引发剂引发油相中的单体在水油界面发生自由基聚合形成高聚物壁层，将芯材包埋其中；形成的壁材是完全覆盖在芯材的表面上，对芯材的包埋率高，形成的纳米胶囊粒径均一且小于150nm；本发明制备的纳米胶囊及制备过程都是绿色环保，制备的纳米胶囊对人体无害，在香精香料、生物医药、日用化妆品及纺织纳米胶囊等行业有广泛的应用前景。
附图说明
图1为本发明中以亚微米液滴成核，在一定温度及N2环境下，引发剂引发油相中的单体发生自由基聚合形成高聚物壁层的机理示意图；
图2为纳米胶囊的透射电镜图；
图3为纳米胶囊的粒径分布图；
图4为纳米胶囊温敏性图。
具体实施方式
下面结合具体实施方式，进一步阐述本发明。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。此外应理解，在阅读了本发明讲授的内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。
实施例1～5
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将1.5份十二烷基磺酸钠和10份去离子水混合，得到水相；
(2)将10份芯材、6份N,N-二乙基丙烯酰胺、6份N,N-二甲基丙烯酰胺、1份二甲基丙烯酸乙二醇酯、0.1份偶氮二异丁腈和1份十六烷混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以6000rpm的剪切速率剪切3min形成微乳液，再以50％的振幅超声10min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，40℃反应3h，得到温敏性纳米胶囊。
当芯材为奥克立林、二苯酮－3、水杨酸辛酯、巴松1789或甲氧基肉桂酸异辛酯时，制得的温敏性纳米胶囊为将芯材包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，温敏性纳米胶囊的基本性能如下表所示。
Figure PCTCN2016088133-appb-000012
实施例6～10
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将2份十二烷基磺酸钠和15份去离子水混合，得到水相；
(2)将20份芯材、8份N,N-二乙基丙烯酰胺、6份N,N-二甲基丙烯酰胺、5份二甲基丙烯酸1,4-丁二醇酯、0.2份偶氮二异丁腈和1.1份十六烷混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以6500rpm的剪切速率剪切4min形成微乳液，再以50％的振幅超声12min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，42℃反应4h，得到温敏性纳米胶囊。
当芯材为薄荷素油、玫瑰香精、柠檬香精、薰衣草香精或绿茶香精时，制得的温敏性纳米胶囊为将芯材包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，温敏性纳米胶囊的基本性能如下表所示。
Figure PCTCN2016088133-appb-000013
实施例11～15
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将3份十二烷基磺酸钠和20份去离子水混合，得到水相；
(2)将50份水清莲花香精、N,N-二乙基丙烯酰胺、N,N-二甲基丙烯酰胺、2份二甲基丙烯酸1,6-己二醇酯、0.3份偶氮二异丁腈和1.2份十六烷混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以7000rpm的剪切速率剪切5min形成微乳液， 再以50％的振幅超声15min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，45℃反应3h，得到温敏性纳米胶囊。
当N,N-二乙基丙烯酰胺的重量份数分别为14份、12份、10份、8份和6份，N,N-二甲基丙烯酰胺的重量份数分别为6份、8份、10份、12份和14份时，制得的温敏性纳米胶囊为将水清莲花香精包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，温敏性纳米胶囊的温敏性图如图4所示，相关数据及其它性能结果如下表所示。
Figure PCTCN2016088133-appb-000014
实施例16
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将4.5份阿拉伯树胶和26份去离子水混合，得到水相；
(2)将66份花香香精、7份N-异丙基丙烯酰胺、8份N-乙基丙烯酰胺、3份二甲基丙烯酸乙二醇酯与二甲基丙烯酸1,4-丁二醇酯的混合物(质量比为1:1)、0.4份偶氮二异丁腈和1.5份十六烷混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以7500rpm的剪切速率剪切6min形成微乳液，再以50％的振幅超声18min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，46℃反应3h，得到温敏性纳米胶囊，反应过程中，以亚微米液滴成核，偶氮二异丁腈引发油相中的N-异丙基丙烯酰胺和N-乙基丙烯酰胺发生自由基聚合形成高聚物壁层，反 应机理示意图如图1所示。
测试表明，制得的温敏性纳米胶囊为将花香香精包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，透射电镜下显示该微胶囊为球形，有明显的核壳结构，分散性好，无聚集状大颗粒，如图2所示，具有温敏性纳米胶囊的包埋率为93％，形成的纳米胶囊粒径PDI为0.1，粒径为140～149nm，如图3所示。
实施例17
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将4份阿拉伯树胶和30份去离子水混合，得到水相；
(2)将70份石蜡、9份N-异丙基丙烯酰胺、10份N-乙基丙烯酰胺、4份二甲基丙烯酸1,4-丁二醇酯与二甲基丙烯酸1,6-己二醇酯的混合物(质量比为1:2)、0.5份偶氮二异丁腈和1.6份十六烷混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以8000rpm的剪切速率剪切3min形成微乳液，再以50％的振幅超声20min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，50℃反应3h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将石蜡包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为94％，形成的纳米胶囊粒径PDI为0.15，粒径为110～130nm。
实施例18
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将3份阿拉伯树胶和35份去离子水混合，得到水相；
(2)将75份正十四烷、11份N-异丙基丙烯酰胺、12份N-乙基丙烯酰胺、5份二甲基丙烯酸乙二醇酯、二甲基丙烯酸1,4-丁二醇酯与二甲基丙烯酸1,6-己二醇酯的混合物(质量比为1:1:1)、0.6份偶氮二异丁腈和1.7份十六烷混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以8500rpm的剪切速率剪切3min形成微乳液，再以50％的振幅超声22min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，52℃反应4h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将正十四烷包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为94％，形成的纳米胶囊粒径PDI为0.15，粒径为130～149nm。
实施例19
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将1.5份水解度为80％的聚乙烯醇和40份去离子水混合，得到水相；
(2)将80份正十五烷、13份N-叔丁基丙烯酰胺、14份N-正丙基丙烯酰胺、1份二甲基丙烯酸乙二醇酯、0.7份偶氮二异丁腈和1.8份十六醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以9000rpm的剪切速率剪切3min形成微乳液，再以50％的振幅超声23min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，55℃反应4h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将正十五烷包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为91％，形成的纳米胶囊粒径PDI为0.11，粒径为110～130nm。
实施例20
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将2份水解度为80％的聚乙烯醇和45份去离子水混合，得到水相；
(2)将85份正十六烷、12份N-叔丁基丙烯酰胺、14份N-正丙基丙烯酰胺、2份二甲基丙烯酸乙二醇酯、0.8份过氧化苯甲酰和1.9份十六醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以9500rpm的剪切速率剪切3min形成微乳液，再以50％的振幅超声24min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，60℃反应3h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将正十六烷包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为92％，形成的纳米胶囊粒径PDI为0.11，粒径为110～130nm。
实施例21
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将3份水解度为80％的聚乙烯醇和50份去离子水混合，得到水相；
(2)将90份正十七烷、8份N-叔丁基丙烯酰胺、13份N-正丙基丙烯酰胺、3份二甲基丙烯酸乙二醇酯、0.1份过氧化苯甲酰和2份十六醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以10000rpm的剪切速率剪切4min形成微乳液，再以50％的振幅超声25min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，62℃反应3h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将正十七烷包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为93％，形成的纳米胶囊粒径PDI为0.12，粒径为110～130nm。
实施例22
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将1.5份水解度为85％的聚乙烯醇和55份去离子水混合，得到水相；
(2)将95份正十八烷、7份N-甲基,N-乙基丙烯酰胺、6份N,N-二乙基丙烯酰胺、4份二甲基丙烯酸乙二醇酯、0.2份过氧化苯甲酰和2.1份十六醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以6000rpm的剪切速率剪切4min形成微乳液，再以50％的振幅超声26min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，65℃反应4h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将正十八烷包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为94％，形成的纳米胶囊粒径PDI为0.12，粒径为110～130nm。
实施例23
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将3份水解度为85％的聚乙烯醇和60份去离子水混合，得到水相；
(2)将100份正十九烷、9份N-甲基,N-乙基丙烯酰胺、8份N,N-二乙基丙烯酰胺、5份二甲基丙烯酸1,4-丁二醇酯、0.3份过氧化苯甲酰和2.2份十六醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以6200rpm的剪切速率剪切4min形成微乳液，再以50％的振幅超声28min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，66℃反应4h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将正十九烷包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为90％，形成的纳米胶囊粒径PDI为0.13，粒径为110～130nm。
实施例24
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将4.5份水解度为85％的聚乙烯醇和65份去离子水混合，得到水相；
(2)将105份正二十烷、11份N-甲基,N-乙基丙烯酰胺、10份N,N-二乙基丙烯酰胺、1份二甲基丙烯酸1,4-丁二醇酯、0.4份过氧化苯甲酰和2.3份十六醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以6600rpm的剪切速率剪切5min形成微乳液，再以50％的振幅超声29min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，68℃反应4h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将正二十烷包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为90％，形成的纳米胶囊粒径PDI为0.13，粒径为110～130nm。
实施例25
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将1.8份水解度为86％的聚乙烯醇和70份去离子水混合，得到水相；
(2)将110份正二十一烷、11份N,N-二甲基丙烯酰胺、8份N-甲基,N-乙基丙烯酰胺、2份二甲基丙烯酸1,4-丁二醇酯、0.5份过氧化苯甲酰和2.4份十六醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以6800rpm的剪切速率剪切5min形成微乳液，再以50％的振幅超声30min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，70℃反应3h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将正二十一烷包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为91％，形成的纳米胶囊粒径PDI为0.14，粒径为110～130nm。
实施例26
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将2.2份水解度为86％的聚乙烯醇和75份去离子水混合，得到水相；
(2)将115份正二十二烷、13份N,N-二甲基丙烯酰胺、10份N-甲基,N-乙基丙烯酰胺、3份二甲基丙烯酸1,4-丁二醇酯、0.6份过氧化苯甲酰和2.5份十六醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以7000rpm的剪切速率剪切5min形成微乳液，再以50％的振幅超声10min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，72℃反应3h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将正二十二烷包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为91％，形成的纳米胶囊粒径PDI为0.14，粒径为90～110nm。
实施例27
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将2.8份水解度为86％的聚乙烯醇和80份去离子水混合，得到水相；
(2)将120份正二十三烷、14份N,N-二甲基丙烯酰胺、12份N-甲基,N-乙基丙烯酰胺、4份二甲基丙烯酸1,4-丁二醇酯、0.1份偶氮二异丁腈和1份十八烷基硫醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以7500rpm的剪切速率剪切6min形成微乳液，再以50％的振幅超声11min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，75℃反应4h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将正二十三烷包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为92％，形成的纳米胶囊粒径PDI为0.15，粒径为90～110nm。
实施例28
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将1.5份水解度为88％的聚乙烯醇和85份去离子水混合，得到水相；
(2)将100份正二十四烷、6份N-异丙基丙烯酰胺、7份N-叔丁基丙烯酰胺、3份二甲基丙烯酸1,6-己二醇酯、0.2份偶氮二异丁腈和1.5份十八烷基硫醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以8000rpm的剪切速率剪切6min形成微乳液，再以50％的振幅超声12min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，76℃反应4h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将正二十四烷包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为92％，形成的纳米胶囊粒径PDI为0.15，粒径为90～110nm。
实施例29
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将2份水解度为88％的聚乙烯醇和90份去离子水混合，得到水相；
(2)将130份维生素油、9份N-异丙基丙烯酰胺、10份N-叔丁基丙烯酰胺、4份二甲基丙烯酸1,6-己二醇酯、0.3份过氧化苯甲酰和1.6份十八烷基硫醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以8200rpm的剪切速率剪切6min形成微乳液，再以50％的振幅超声15min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，78℃反应3h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将维生素油包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为93％，形成的纳米胶囊粒径PDI为0.15，粒径为90～110nm。
实施例30
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将3份水解度为88％的聚乙烯醇和10份去离子水混合，得到水相；
(2)将110份抗肿瘤药物、12份N-异丙基丙烯酰胺、14份N-叔丁基丙烯酰胺、5份二甲基丙烯酸1,6-己二醇酯、0.4份过氧化苯甲酰和1.8份十八烷基硫醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以9000rpm的剪切速率剪切3min形成微乳液，再以50％的振幅超声16min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，60℃反应4h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将抗肿瘤药物包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为93％，形成的纳米胶囊粒径PDI为0.16，粒径为90～110nm。
实施例31
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将1.5份水解度为90％的聚乙烯醇和35份去离子水混合，得到水相；
(2)将116份芯材奥克立林与玫瑰香精的混合物(质量比为1:1)、6份N-乙基丙烯酰胺、10份正丙基丙烯酰胺、2份二甲基丙烯酸乙二醇酯与二甲基丙烯酸1,4-丁二醇酯的混合物(质量比为1:1)、0.5份偶氮二异丁腈和2份十八烷基硫醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以9200rpm的剪切速率剪切4min形成微乳液，再以50％的振幅超声18min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，66℃反应3h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将芯材包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为94％，形成的纳米胶囊粒径PDI为0.16，粒径为90～110nm。
实施例32
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将2份水解度为90％的聚乙烯醇和52份去离子水混合，得到水相；
(2)将118份芯材二苯酮－3、玫瑰香精、石蜡和抗肿瘤药物的混合物(质量比为1:1:1:1)、12份N-乙基丙烯酰胺、12份正丙基丙烯酰胺、3份二甲基丙 烯酸1,4-丁二醇酯与二甲基丙烯酸1,6-己二醇酯的混合物(质量比为1:2)、0.6份偶氮二异丁腈和2.2份十八烷基硫醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以9500rpm的剪切速率剪切5min形成微乳液，再以50％的振幅超声20min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，75℃反应4h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将芯材包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为94％，形成的纳米胶囊粒径PDI为0.17，粒径为90～110nm。
实施例33
一种温敏性纳米胶囊的制备方法，制备步骤为：
(1)配制乳化剂水溶液：将3份水解度为90％的聚乙烯醇和63份去离子水混合，得到水相；
(2)将150份芯材巴松1789、花香香精和正十七烷的混合物(质量比为1:1:1)、14份N-乙基丙烯酰胺、14份正丙基丙烯酰胺、4份二甲基丙烯酸乙二醇酯、二甲基丙烯酸1,4-丁二醇酯与二甲基丙烯酸1,6-己二醇酯的混合物(质量比为1:1:1)、0.8份过氧化苯甲酰和2.5份十八烷基硫醇混合，搅拌均匀，得到油相；
(3)将水相加入到油相中，以10000rpm的剪切速率剪切6min形成微乳液，再以50％的振幅超声30min形成纳米乳液；
(4)在形成纳米乳液之后持续通入氮气保护至反应结束，80℃反应3h，得到温敏性纳米胶囊。
测试表明，制得的温敏性纳米胶囊为将芯材包埋在为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层中，具有温敏性纳米胶囊的包埋率为94％，形成的纳米胶囊粒径PDI为0.17，粒径为90～110nm。

Claims (10)

  1. 温敏性纳米胶囊的制备方法，其特征是：采用两种不同的N-烷基丙烯酰胺单体进行自由基聚合形成壁材，制得温敏性纳米胶囊；
    制备步骤为：
    (1)配制乳化剂水溶液：将乳化剂和去离子水混合，得到水相；
    (2)将芯材、两种不同的N-烷基丙烯酰胺单体、交联剂、引发剂和共稳定剂混合，搅拌均匀，得到油相；
    (3)将水相加入到油相中，剪切形成微乳液，再超声形成纳米乳液；
    (4)向所述纳米乳液通入氮气，40-80℃反应，得到温敏性纳米胶囊；
    其中N-烷基丙烯酰胺单体的结构通式为：
    Figure PCTCN2016088133-appb-100001
    R1为
    Figure PCTCN2016088133-appb-100002
    R2为
    Figure PCTCN2016088133-appb-100003
    或—H；
    m1＝2,3,4…；m2＝1,2,3,4…；
    其中交联剂的结构通式为：
    Figure PCTCN2016088133-appb-100004
    R1为
    Figure PCTCN2016088133-appb-100005
    R2为
    Figure PCTCN2016088133-appb-100006
    或-H；
    R3为
    Figure PCTCN2016088133-appb-100007
    或-H；
    R4为
    Figure PCTCN2016088133-appb-100008
    或-H；
    n1＝2，3，4...；n2＝1，2，3，4...；n3＝2，3，4...；n4＝1，2，3，4...； n5＝2,3,4…；n6＝1,2,3,4…；n7＝2,3,4…；n8＝1,2,3,4…。
  2. 根据权利要求1所述的温敏性纳米胶囊的制备方法，其特征在于，所述乳化剂为十二烷基磺酸钠、阿拉伯树胶或水解度为80～90％的聚乙烯醇。
  3. 根据权利要求1所述的温敏性纳米胶囊的制备方法，其特征在于，所述芯材为紫外吸收剂、香精香料、相变材料和医药中的至少一种；所述紫外吸收剂为奥克立林或二苯酮－3或水杨酸辛酯或巴松1789或甲氧基肉桂酸异辛酯；所述香精香料为薄荷素油或玫瑰香精或柠檬香精或薰衣草香精或绿茶香精或水清莲花香精或花香香精；所述相变材料为石蜡或正十四烷或正十五烷或正十六烷或正十七烷或正十八烷或正十九烷或正二十烷或正二十一烷或正二十二烷或正二十三烷或正二十四烷；所述医药为维生素油或抗肿瘤药物。
  4. 根据权利要求1所述的温敏性纳米胶囊的制备方法，其特征在于，所述单体为N,N-二乙基丙烯酰胺或N,N-二甲基丙烯酰胺或N-异丙基丙烯酰胺或N-乙基丙烯酰胺或N-叔丁基丙烯酰胺或N-正丙基丙烯酰胺或N-甲基,N-乙基丙烯酰胺。
  5. 根据权利要求1所述的温敏性纳米胶囊的制备方法，其特征在于，所述交联剂为二甲基丙烯酸乙二醇酯、二甲基丙烯酸1,4-丁二醇酯和二甲基丙烯酸1,6-己二醇酯中的至少一种。
  6. 根据权利要求1所述的温敏性纳米胶囊的制备方法，其特征在于，所述引发剂为偶氮二异丁腈或过氧化苯甲酰；所述共稳定剂为十六烷或十六醇或十八烷基硫醇。
  7. 根据权利要求1所述的温敏性纳米胶囊的制备方法，其特征在于，所述水相和油相中，按重量份数计，各组分为：
    Figure PCTCN2016088133-appb-100009
    Figure PCTCN2016088133-appb-100010
  8. 根据权利要求1所述的温敏性纳米胶囊的制备方法，其特征在于，所述剪切的剪切速率为6000～10000rpm，剪切时间为3～6min；所述超声的振幅为50％，超声时间为10～30min。
  9. 根据权利要求1所述的温敏性纳米胶囊的制备方法，其特征在于，所述通入氮气是指在形成纳米乳液之后持续通入氮气保护至反应结束；所述反应的时间为3h～4h。
  10. 如权利要求1～9中任一方法所制得的温敏性纳米胶囊，其特征是：所述温敏性纳米胶囊为将芯材包埋在高聚物壁层中，所述高聚物壁层为由油相中的单体在水油界面发生自由基聚合而形成高聚物壁层；所述具有温敏性纳米胶囊的包埋率为90％～94％，形成的纳米胶囊粒径PDI为0.09～0.17且粒径<150nm。
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