CN105131164A - Method for preparing monodisperse polymeric microspheres adopting snowman-shaped, dumbbell-shaped, raspberry-shaped or core-shell structure through one-step dispersion polymerization - Google Patents

Abstract

The invention discloses a method for preparing monodisperse polymeric microspheres adopting a snowman-shaped, dumbbell-shaped, raspberry-shaped or core-shell structure through one-step dispersion polymerization, and belongs to a dispersion polymerization technology. According to the method, all reaction reagents (including monomers, a cross-linking agent, initiator, functional monomers and the like) are added in one step, and the polymeric microspheres adopting the snowman-shaped, dumbbell-shaped, raspberry-shaped or core-shell structure are prepared through dispersion polymerization. The method is simple and effective.

Description

Method for preparing monodisperse polymer microspheres of snowman, dumbbell, raspberry or core-shell structure by one-step dispersion polymerization

technical field

The present invention relates to a method for directly preparing monodisperse functional polymer microspheres of snowman shape, dumbbell shape, raspberry shape and core-shell structure through one-step dispersion polymerization, especially relates to utilizing initial step to add all reaction reagents (comprising monomer, crosslinking agent, initiator, etc.) to prepare snowman-shaped, dumbbell-shaped, raspberry-shaped and core-shell polymer microspheres by dispersion polymerization, which belongs to the dispersion polymerization technology.

Background technique

Dispersion polymerization starts from a homogeneous system, that is, monomers, stabilizers, initiators and other reagents are all dissolved in the reaction medium at the beginning; as the polymerization reaction proceeds, the generated polymer chain reaches a critical chain length and is removed from the reaction medium. Precipitation, precipitation, nucleation - this stage is the nucleation period; after that, the monomer diffuses into the particle phase and reacts to make the particle grow, and the monomer can also react at the interface between the particle and the medium and in the continuous phase. The phase is the particle growth period, and the reaction is similar to the seed polymerization.

By adding functional reagents at the beginning of dispersion polymerization, polymer microspheres containing specific functional groups can be easily obtained. However, when the functional reagents such as crosslinking agent and hydrophilic comonomer (such as acrylic acid-AA) are added at the beginning of polymerization, and their content is relatively large (1wt.%, relative to the weight percentage of the main monomer, wt.%), the system The stability and monodispersity of the microspheres are easily destroyed, the microspheres are easy to stick to each other and the particle size distribution becomes broad. For example, the cross-linking agent quickly reacts to form a cross-linked structure, which shrinks the growing particles, which is not conducive to the diffusion of continuous phase monomers to the particle phase, and increases the polymerization of monomers in the continuous phase, resulting in secondary nucleation (SongJ.S., WinnikM. A., et.al., J.Am.Chem.Soc., 2004, 126, 6562-6563; Macromolecules, 2005, 38, 8300-8307; Macromolecules, 2006, 39, 8318-8325); hydrophilic monomer Copolymerization increases the solubility of oligomers in the continuous phase, resulting in a longer nucleation period and a wider particle size distribution (ZhangH.T, Yuan, X.Y., HuangJ.X., Reactive&Functional Polymers, 2004, 59, 23-31) .

In order to solve the above problems, Winnik M.A. etc. adopted functional monomers such as cross-linking agents after the nucleation period, that is, a two-step feeding dispersion polymerization method (2-Dis.P.), and obtained monodisperse uniform cross-linking, only Shell crosslinking (core-shell structure, PengB., WeeE., ImhofA., BlaaderenA., Langmuir, 2012, 28, 6776-6785; WangS.L., YueK., LiuL.Y., YangW.T., J .ColloidInterfaceSci., 2013, 389, 126-133; WangS.L., YangX.F., LiuL.Y., YangW.T., ChineseJ.Polym.Sci., 2012, 30, 865-872), or some regions are highly cross-linked (Dimple-shaped, CongH.L., WangJ.L, YuB., TangJ.G., CuiW., J.ColloidInterfaceSci., 2013, 411, 41-46) polymer microspheres. In addition, ZengZ.H et al. used one-step feeding, photoinitiated RAFT dispersion polymerization (both photoinitiator and RAFT reagents were added at the beginning) to simply and directly prepare monodisperse, highly cross-linked functional polymer microspheres (TanJ.B. , RaoX., YangJ.W., ZengZ.H., Macromolecules, 2012, 45, 8790-8795; Macromolecules, 2013, 46, 8441-8448; Macromolecules, 2014, 47(19), 6856-6866; RSCAdv., 2015, May, 18922-18931). ShimS.E. etc. also obtained monodisperse crosslinked polymer microspheres by using longer chain crosslinkers to reduce crosslink density in one-step feeding dispersion polymerization (ShimS.E., JungH., LeeK., LeeJ.M., Choe S.J. Colloid Interf. Sci., 2004, 279, 464-470; Kim J.W., Suh K.D., Colloid Polym. Sci., 1999, 277, 210-216). The above studies mainly focus on whether monodisperse spherical functional polymer microspheres can be obtained, and rarely involve non-spherical (such as snowman-shaped, dumbbell-shaped) polymer microspheres; generally, the microspheres obtained by one-step dispersion polymerization are spherical, smooth surface, Polymer microspheres with uniform crosslinking (crosslinking at the beginning of polymerization) are not easy to obtain polymer microspheres with rough surface (raspberry shape) and/or uneven crosslinking (core-shell structure, only shell crosslinking).

Compared with spherical polymer microspheres, non-spherical microspheres have asymmetry or inhomogeneity in shape, structure, composition, etc., which makes them unique and unique in applications such as emulsion stabilization, photoelectric display, biosensing, and catalysis. Excellent performance. Many methods for preparing non-spherical polymer microspheres have been developed at present, among which, the seed phase separation polymerization method (MockE.B., DeBruynH., HawkettB.S., GilbertR.G., ZukoskiC.F., Langmuir2006,22(9 ), 4037-4043; Kim J.W., LarsenR.J., WeitzD.A., J.Am.Chem.Soc.2006, 128, 14374-14377; ZhangC.L., QuX.Z., LiJ.L ., QiuD., YangZ.Z., Macromolecules, 2012, 45(12), 5176-5184; PengB., VutukuriH.R., BlaaderenA., ImhofA., J. Mater.Chem., 2012, 22, 21893- 21900; ThomasS.S., ChenY.H., BonS.A.F., Langmuir, 2014, 30, 13525-13532), that is, using spherical microspheres obtained by dispersion and emulsion polymerization as seeds and undergoing monomer swelling, heating, and phase separation 1. The method for preparing snowman-shaped or dumbbell-shaped microspheres by polymerization is a method generally recognized and capable of preparing non-spherical microspheres in large quantities. However, this method still has some limitations: if it involves many steps (including seed preparation, crosslinking and surface modification, etc.), swelling and crosslinking seeds takes time, and the morphology, size and surface roughness of each part of non-spherical microspheres cannot be effectively continuous control etc. In response to these problems, Yang W.T. et al. proposed to use the characteristics of dispersion polymerization to adopt a two-step dispersion polymerization method, that is, to add crosslinking agents, initiators and functional monomers during the growth period of one-pot dispersion polymerization particles to control the uneven cross-linking of growing particles. Link or form a dense cross-linked shell, so that the cross-linked growth particles swollen by monomers, oligomers or low-molecular-weight polymers undergo phase separation during the reaction process, and prepare snowman-shaped, dumbbell-shaped or multi-part functional polymers Microspheres (LiuY.N., YangQ., ZhuJ.M., LiuL.Y., YangW.Y. ColloidPolym.Sci., 2015, 293, 523-532; LiuY.N., MaY.H., LiuL.Y. , YangW.Y., JColloidInterf.Sci., 2015, 445, 268-276; LiuY.N., LiuW., MaY.H., LiuL.Y., YangW.Y., Langmuir, 2015, 31(3), 925 -936; Liu Lianying, Yang Qing, Yang Wantai, Ma Yuhong, Liu Yanan, Liu Wang, One-pot dispersion polymerization method for preparing non-spherical, raspberry-shaped and hollow polymer microspheres, Chinese invention patent, application number: CN201310717922). However, this method still requires two-step feeding, and it cannot prepare non-spherical polymer microspheres by initial one-step feeding like the preparation of conventional spherical particles.

Compared with spherical polymer microspheres with smooth surface, raspberry-like microspheres have many small particles or protrusions on the surface, with large roughness and large specific surface area. protrude. Generally, raspberry-like microspheres can be formed in three ways: (1) large-core particles and small particles are composited through hydrogen bonding, electrostatic or acid-base interactions; (3) Use small particles as surfactant to carry out Pickering emulsion polymerization. Obviously, these method steps are relatively complicated. At present, there have been reports (SunY.Y., YinY.Y., ChenM., ZhouS.X., WuL.M., Polym.Chem ., 2013, 4, 3020-3027), but this method involves the pre-hydrolysis and surface coagulation of 3-(trimethoxysilane) propyl acrylate-MPS, which is not suitable for other systems, which limits its application. Studies by Liu Lianying and others have shown that raspberry-like polymer microspheres can be prepared by one-pot dispersion polymerization and two-step feeding method (Liu Lianying, Yang Qing, Yang Wantai, Ma Yuhong, Liu Yanan, Liu Wang, one-pot dispersion polymerization to prepare non-spherical, raspberry-like and the method of hollow polymer microspheres, Chinese invention patent, application number: CN201310717922), but it does not involve simpler, initial one-step feeding dispersion polymerization to prepare raspberry-like polymer microspheres.

Contents of the invention

The purpose of the present invention is to provide a simple one-pot, one-step dispersion polymerization method for preparing snowman-shaped, dumbbell-shaped, raspberry-shaped or core-shell structured monodisperse polymer microspheres. That is: at the beginning, all the reaction reagents such as monomers, crosslinking agents, and initiators are dissolved in the dispersion medium, and then the temperature is raised to carry out polymerization. During the polymerization process, there is no need to add other reagents such as monomers, and the snowman shape or dumbbell shape is obtained after the reaction. , or raspberry-like or core-shell structured monodisperse polymer microspheres.

The technical scheme that the present invention adopts for realizing the above object is:

The monomer styrene-St, sodium styrene sulfonate-NaSS, initiator azobisisobutyronitrile-AIBN and crosslinking agent are stirred and dissolved in the mixed solution of organic solvent and water to form a reaction solution; the reaction solution temperature Rise to 75°C to start the reaction for a certain period of time to obtain snowman-shaped, or dumbbell-shaped, or raspberry-shaped, or monodisperse polymer microspheres with a core-shell structure.

The cross-linking agent is a cross-linking agent monomer A with double bonds at two end groups, or a cross-linking agent monomer B with double bonds at three end groups, or a double bond at one end group and a triple bond at one end group. Linking agent monomer C, or cross-linking agent monomer D whose two terminal groups are triple bonds.

A functional monomer is also added to the above reaction solution, and the amount of the functional group monomer is 1-6 wt.% of the amount of St.

Specific steps are as follows:

Place the reactor equipped with stirrer and reflux condensing device in a constant temperature water bath, add the mixed solution of organic solvent and water, then add monomer St, NaSS, initiator AIBN and crosslinking agent, stir to form a reaction solution (rotating speed is preferably 200r/min); raise the temperature of the reaction solution to 75°C, and react for 8 hours; centrifuge the final dispersion, pour it to remove the supernatant, then add methanol to wash and centrifuge, and repeat the operation at least 3 times to obtain a powder sample. Dry to constant weight.

Further, when adding monomer St, NaSS, initiator AIBN and crosslinking agent, functional monomers are also added, and the functional monomers are preferably selected from the following monomers: epoxy-containing monomers, carboxyl-containing monomers , amide-containing monomers, pyridyl-containing monomers, and alkynyl-containing monomers, and more preferably the terminal groups are the above-mentioned groups.

The organic solvent in the mixed liquid of the organic solvent and water used is selected from one or more of ethylene glycol, ethanol and methanol, and the organic solvent accounts for 60-80% of the total volume of the mixed liquid of the organic solvent and water.

The concentration of the monomer St used is 8-15wt.% (wt.% by weight in the reaction solution), the amount of NaSS is 1-4wt.% of St; the amount of the initiator used is 1-3wt.% of St. %.

Used linking agent A can be-contain the monomer of two double bonds, and its chemical structure is as follows:

Among them: R ₁ and R ₂ can be H or CH ₃ ; R ₃ can be a benzophenone unit, a fluorescein unit Or the structure of ethoxy -CH ₂ -CH ₂ -O- unit.

For example, the above-mentioned crosslinking agent containing two double bonds can be: 4,4'-Dimethacryloxybenzophenone-DMABP:

or 4,4'-Dimethacryloxyfluorescein-DMA-Fluo:

or polyethylene glycol diacrylate - PEGDA: Preferably its molecular weight Mn=575 (PEGDA575), 700 (PEGDA700);

The crosslinking agent used can also be B-monomer containing three double bonds, such as acrylate monomer, trimethylolpropane triacrylate-TMPTA:

The cross-linking agent used can also be a C-monomer containing a double bond and a triple bond, such as: propargyl acrylate-PGA: or propargyl methacrylate-PMA:

The cross-linking agent used can also be D-monomer containing two triple bonds, such as: 1,7-octadiyne-OTD:

One kind of cross-linking agent can be used alone, or two kinds of cross-linking agents can be used in combination, and the amount of cross-linking agent used is 1-20 wt.% of St.

In addition, monomers containing specific functional groups can be added to the reaction system, such as monomers containing epoxy groups: glycidyl methacrylate-GMA; monomers containing carboxyl groups: acrylic acid-AA, methacrylic acid-MAA; Amide monomer: N-isopropylacrylamide-NIPAM; pyridyl-containing monomer: 4-vinylpyridine (4-VP); alkyne-containing monomer: propargyl acetate-PAT Propargyl Bromide-PBR Propynyl bromoisobutyrate-PGBB or 1-hexyne (HE, HC≡C(CH ₂ ) ₃ CH ₃ ). The amount of the above-mentioned monomers containing specific functional groups is 1-6 wt.% (wt.% relative to St).

In the present invention, different types of cross-linking agents or/and functional monomers are used, the polymerization reaction rate is different, and the cross-linking, swelling degree and surface hydrophilicity of the growth particles formed in the reaction process are different, resulting in the division of cross-link growth particles. The degree of phase is different, resulting in different morphology (snowman shape, dumbbell shape and raspberry shape), structure (cross-linked or not cross-linked, core-shell structure), surface roughness (smooth and rough) and distribution of surface functional groups polymer microspheres. The obtained polymer microspheres have a part with smooth or rough surface or obvious protrusions and internal cross-linking, while the other part has smooth surface, no internal cross-linking or partial cross-linking or core (sparsely cross-linked or non-cross-linked)-shell ( Dense cross-linked) structure snowman-shaped or dumbbell-shaped polymer microspheres; the obtained polymer microspheres are raspberry-shaped polymer microspheres with rough or flower-like surfaces and uniform or gradient cross-linked interiors. The obtained polymer microsphere is a polymer microsphere with a smooth or rough surface and a core (sparsely cross-linked or non-cross-linked)-shell (dense cross-linked) structure.

For example: if the A crosslinking agent containing benzophenone or fluorescein unit structure is used alone, the crosslinking growth particles can be swelled by monomers and oligomers during the polymerization process, causing elastic stress in the particles; in order to release the elasticity Under stress, the particles undergo phase separation, and finally a part of the surface is rough and internally crosslinked (containing benzophenone or fluorescein unit structure), while another part of the surface is smooth and internally non-crosslinked snowman-like polymer microspheres (see Example 1-2, accompanying drawing 1a); Or obtain two parts surface all smooth, a part crosslinking (containing benzophenone or fluorescein unit structure), and another part is not crosslinked snowman shape polymer microsphere (see embodiment 3-4 and accompanying drawing 1b); Or obtain a part of rough surface, internal cross-linking, and another part of smooth surface, internal part of cross-linking, neck has a plurality of small protrusions, benzophenone or fluorescein unit structure distribution is not Uniform snowman-shaped polymer microspheres (see embodiment 5 and accompanying drawing 1c); or obtain a part of rough surface (multiple obvious small protrusions appear), internal crosslinking, and another part of snowman-shaped surface smooth, internal non-crosslinked Polymer microspheres (see accompanying drawing 1d of embodiment 6-7); Or obtain core-shell structure polymer microspheres with sparse internal crosslinking and dense external crosslinking and smooth surface (see embodiment 8 and accompanying drawing 4a).

When A crosslinker containing benzophenone or fluorescein unit structure is used together with C crosslinker such as PGA or PMA, due to the different reactivity of double bond and triple bond in C crosslinker, the double bond can react preferentially , and the three-bond hysteresis reaction, thus obtaining a rough surface, internal partly cross-linked, partly snowman-like polymer microspheres of core-shell (cross-linked) structure (see embodiment 9 and accompanying drawing 1e); or obtain a part The surface is rough and uniformly cross-linked, and another part of the surface is smoother and has a dumbbell-shaped polymer microsphere with a core-shell (cross-linked) structure (seeing examples 10-11 and accompanying drawing 2a); Dumbbell-shaped polymer microspheres (seeing examples 12-13 and accompanying drawing 2b) with a smoother surface and a core-shell (crosslinked) structure (seeing examples 12-13 and accompanying drawing 2b); or Polymer microspheres with a smooth surface and a core (non-crosslinked)-shell (dense crosslinked) structure were obtained (see Example 14 and accompanying drawing 4b).

When A cross-linking agent containing benzophenone or fluorescein unit structure is used together with D cross-linking agent such as OTD, one part of the surface is rough (with multiple obvious small protrusions) and internal cross-linking, while the other part has a smooth surface 1. Snowman-shaped polymer microspheres without internal cross-linking (see Example 15 and accompanying drawing 1d).

When the A crosslinking agent containing benzophenone or fluorescein unit structure is used together with different functional monomers, the surface properties and swelling degree of the growing particles are different during the polymerization process, and the structure, morphology and function of the obtained polymer microspheres are different. The positions of the groups are different. When used together with epoxy group-containing monomers such as GMA, dumbbell-shaped polymer microspheres with a part of the surface rough (small dot protrusions appearing, containing epoxy groups) and cross-linked, while the other part of the surface is smooth and non-cross-linked can be obtained (see embodiment 16 and accompanying drawing 2c). When used together with carboxyl-containing monomers such as AA and MAA, a part of the surface is rough (multiple obvious protrusions appear, containing carboxyl groups) and cross-linked, while the other part of the surface is smooth and non-cross-linked dumbbell-shaped polymer microspheres (see implementation Examples 17-18 and Figure 2d). Add in the system together with amide-containing monomers such as NIPAM, obtain a part of rough surface (containing N-isopropyl), crosslinking, and another part of snowman-like polymer microspheres with smooth surface and no crosslinking (see Example 19 and accompanying drawing 1a). Adding together with pyridyl-containing monomers such as 4-VP, one part of the surface is rough (multiple obvious small protrusions appear, containing pyridyl), cross-linked, and another part of snowman-like polymer microspheres with smooth surface and no cross-linking ( See Example 20 and accompanying drawing 1d).

When used with alkyne-containing monomers such as PAT, PBR, PGBB, HE, etc., since such monomers are not easy to react, they can act as solvents, and the growing particles are easily extruded to the newly formed protrusions when phase separation occurs Finally, a part of the surface is slightly rough and internally crosslinked, and another part of the surface is smooth and internally uncrosslinked snowman-shaped polymer microspheres (see Examples 21-24 and accompanying drawing 1f).

In addition, when an ethoxy-containing A crosslinking agent such as PEGDA575 or PEGDA700 is used alone, a raspberry-like polymer microsphere with a flower-like surface and a gradient crosslinking inside can be obtained through one-step dispersion polymerization (see Examples 25-26 and Accompanying drawing 3a); Or obtain the polymer microsphere (see embodiment 27 and accompanying drawing 4c) that surface is rough, have core (sparse cross-linking)-shell (dense cross-linking) structure; Or obtain rough surface, have core ( Non-crosslinked)-shell (dense crosslinked) structure polymer microspheres (see Example 28 and Figure 4d).

When the B crosslinking agent such as TMPTA is used alone, the particle surface is rough and crosslinked polymer microspheres are obtained (see Example 29 and accompanying drawing 3b).

When C crosslinking agents such as PGA or PMA are used alone, due to the different reactivity of the double bond and triple bond in the crosslinking agent, smooth core (non-crosslinking)-shell (dense crosslinking) polymer microspheres are obtained (see Examples 30-31 and accompanying drawing 4b); Or obtain rough surface core (non-crosslinking)-shell (dense crosslinking) polymer microspheres (see example 32 and accompanying drawing 4d).

After the reaction, the resulting dispersion is processed according to post-processing procedures well known to those skilled in the art: namely, centrifugation, separation, washing and drying to obtain a powder sample.

In order to observe the morphology and structure of the obtained crosslinked microspheres and determine the crosslinking position and degree of crosslinking, the microspheres can be soaked in THF and stirred for 48 hours, during which fresh THF is replaced every 6 hours to remove the uncrosslinked polymer in the particles. .

The sample was ultrasonically dispersed, suspended in methanol, and dropped onto a clean glass sheet or copper grid for sample preparation, using a scanning electron microscope (SEM, Hitachi S-4700, accelerating voltage 20kV)) and a transmission electron microscope (TEM, JEOLJEM-2100, Accelerating voltage 200kV) to observe the morphology and structure of the obtained polymer particles.

Effect of the present invention:

1. In one-step dispersion polymerization, monomers, cross-linking agents, initiators and solvents are all added directly at the beginning of the reaction without additional addition, which simplifies the reaction process. Realized the preparation of snowman-shaped, dumbbell-shaped, raspberry-shaped and core-shell polymer microspheres by one-step dispersion polymerization. The invention provides a simple and effective one-step dispersion polymerization method for directly preparing monodisperse non-spherical/spherical polymer microspheres.

2. In one-step dispersion polymerization, the surface morphology and structure of the polymer microspheres can be adjusted by changing the type and amount of the cross-linking agent, so that a part of the surface is smooth or rough or has obvious protrusions and internal cross-linking, while the other Snowman-shaped or dumbbell-shaped polymer microspheres with a smooth surface, non-crosslinked or partially crosslinked interior, or a core (sparsely crosslinked or non-crosslinked)-shell (densely crosslinked) structure; or a rough or flowery surface Raspberry-like polymer microspheres with homogeneous or gradient cross-linking inside; or polymer microspheres with smooth or rough surface, core (sparse cross-linking or no cross-linking)-shell (dense cross-linking) structure.

3. In the one-step dispersion polymerization, the crosslinking agent and functional monomer are used at the same time, and the polymerization of monomers containing different functional groups and the hysteresis reaction of the triple bond are used to obtain the surface of the initial part containing different functional groups, or the surface of the newly formed part containing Yeti-shaped or dumbbell-shaped polymer microspheres with functional groups.

Description of drawings

Fig.1 SEM and TEM photos of snowman-like polymer microspheres with different shapes, structures and surface roughness

a. Snowman-like polymer microspheres with rough surface and cross-linked surface, and smooth, non-cross-linked surface;

b. Both parts have smooth surfaces, one part is crosslinked and the other part is non-crosslinked snowman-shaped polymer microspheres;

c. A part of the surface is rough and cross-linked, and the other part is smooth and partially cross-linked, and the neck has a plurality of snowman-shaped polymer microspheres with small protrusions;

d. A part of the surface is rough (multiple obvious small protrusions appear), crosslinked, and another part has a smooth surface and non-crosslinked snowman-like polymer microspheres;

e. Snowman-like polymer microspheres with rough surface, partially cross-linked, and partially core-shell (cross-linked) structure;

f. Some snowman-like polymer microspheres with a slightly rough surface and cross-linked surface and a part with a smooth surface and no cross-linked surface.

Fig.2 SEM and TEM photos of dumbbell-shaped polymer microspheres with different shapes, structures and surface roughness

a. A portion of dumbbell-shaped polymer microspheres with a rough surface and uniform cross-linking, while the other portion has a smoother surface and a core-shell (cross-linked) structure;

b. a part of the surface is raspberry-shaped (many obvious small protrusions appear) and uniformly cross-linked, while the other part has a smoother surface and dumbbell-shaped polymer microspheres with a core-shell (cross-linked) structure;

c. A portion of dumbbell-shaped polymer microspheres with a rough surface (small point protrusions) and cross-linking, while the other portion is smooth and non-cross-linked;

d. Dumbbell-shaped polymer microspheres with one part of the surface rough (multiple distinct protrusions) and crosslinked, and the other part with a smooth surface and no crosslinking.

Fig.3 SEM and TEM photos of raspberry-like polymer microspheres with different surface roughness and internal structure

a. Raspberry-like polymer microspheres uniformly cross-linked inside;

b. Raspberry-like polymer microspheres with flower-like surface and internal gradient cross-linking.

Fig.4 SEM and TEM photos of core-shell polymer microspheres with different surface roughness

a. Smooth core (sparsely crosslinked)-shell (densely crosslinked) polymer microspheres;

b. Smooth core (non-crosslinked)-shell (dense crosslinked) polymer microspheres;

c. Core (sparse cross-linking)-shell (dense cross-linking) polymer microspheres with rough surface;

d. Core (non-crosslinked)-shell (dense crosslinked) polymer microspheres with rough surfaces.

Detailed ways

The implementation method of the present invention will be further described by the following examples, but the present invention is not limited to these examples, and also includes: under the condition of not departing from the scope of the present invention, carry out various changes obvious to those skilled in the art to the disclosed method.

Example 1

Put a 100ml three-necked round-bottom reaction flask equipped with mechanical stirring and reflux condenser in a constant temperature water bath, add 15ml of methanol and 10ml of deionized water (methanol/water=6/4, vol.), add monomer styrene St2 .5ml (concentration 10wt.% in the reaction solution), crosslinking agent DMABP0.0906g (4wt.%, relative St weight), sodium styrene sulfonate NaSS0.0453g (2wt.%, relative St weight), initiator couple Azodiisobutyronitrile AIBN0.0453g (2wt.%, relative to the weight of St); start stirring, the rotation speed is 200r/min; at the same time, heat the constant temperature water bath to 75°C to start the reaction, the total reaction time is 8h. Centrifuge the obtained stable micelle dispersion, pour it to remove the supernatant, then add methanol to wash, centrifuge, and repeat this operation at least 3 times to obtain a powder sample, which is dried to a constant weight. SEM and TEM observed that the obtained microspheres were snowman-shaped polymer microspheres with rough surface and internal crosslinking (containing benzophenone unit structure), and another part with smooth surface and no internal crosslinking (see accompanying drawing 1a).

Example 2

Others are as in Example 1, replaced by adding ethanol 17.5ml and deionized water 7.5ml (ethanol/water=7/3, vol.) to the reaction system, adding monomer styrene St2.24ml (concentration in the reaction solution 8wt. %), add cross-linking agent DMA-Fluo0.1133g (5wt.%, relative to the initial St weight). SEM and TEM observed that the obtained microspheres were snowman-shaped polymer microspheres with rough surface and internal crosslinking (containing fluorescein unit structure), and another part with smooth surface and no internal crosslinking (see Figure 1a).

Example 3

Others are as in Example 1, replaced by adding cross-linking agent DMA-Fluo0.0906g (4wt.%, relative to the initial St weight) to the reaction system. SEM and TEM observed that two parts of the microspheres were smooth, one part was cross-linked (containing fluorescein unit structure), and the other part was not cross-linked snowman-shaped polymer microspheres (see Figure 1b).

Example 4

Others are as in Example 1, replaced by adding ethylene glycol 20ml and deionized water 5ml (ethylene glycol/water=8/2, vol.) to the reaction system, adding monomer styrene St3.75ml (concentration in the reaction solution 15wt.%). The obtained microspheres observed by SEM and TEM are snowman-shaped polymer microspheres with two parts having smooth surfaces, one part being cross-linked (containing benzophenone or fluorescein unit structure), and the other part not being cross-linked (see Figure 1b).

Example 5

Others are as in Example 1, except that the amount of DMABP added to the reaction system is 0.1133g (5wt.%, relative to the initial St weight). The microspheres observed by SEM and TEM are a part of the surface is rough and internally cross-linked, while the other part is smooth and internally partially cross-linked, with multiple small protrusions on the neck, and a snowman with uneven distribution of benzophenone or fluorescein unit structure Shaped polymer microspheres (see accompanying drawing 1c).

Example 6

Others are as in Example 1, replaced by adding cross-linking agent DMA-Fluo0.2265g (10wt.%, relative to the initial St weight) to the reaction system. SEM and TEM observations showed that one part of the microspheres had a rough surface (with multiple obvious small protrusions) and internal cross-linking, and the other part had a smooth surface and no internal cross-linking snowman-like polymer microspheres (see Figure 1d).

Example 7

Others are as in Example 1, replaced by adding ethylene glycol 20ml and deionized water 5ml (ethylene glycol/water=8/2, vol.) to the reaction system, adding crosslinking agent DMA-Fluo0.2265g (10wt.%, Relative to the initial weight of St), sodium styrene sulfonate NaSS0.0906g (4wt.%, relative to the weight of St), and initiator azobisisobutyronitrile AIBN0.0680g (3wt.%, relative to the weight of St). SEM and TEM observations showed that one part of the microspheres had a rough surface (with multiple obvious small protrusions) and internal cross-linking, and the other part had a smooth surface and no internal cross-linking snowman-like polymer microspheres (see Figure 1d).

Example 8

Others are as in Example 1, the amount of DMABP added to the reaction system is 0.0227g (1wt.%, relative to the initial weight of St). The obtained microspheres observed by SEM and TEM are core-shell polymer microspheres with sparse internal crosslinking, dense external crosslinking and smooth surface (see Figure 4a).

Example 9

Others as in Example 1, two crosslinking agents were added to the reaction system at the same time: DMABP0.1359g (6wt.%, relative to the initial St weight) and PMA0.15ml (6vol.%, relative to the initial St volume). The obtained microspheres observed by SEM and TEM are snowman-like polymer microspheres with rough surface, partially cross-linked inside, and partially core-shell (cross-linked) structure (see Figure 1e).

Example 10

Others as in Example 1, two crosslinking agents were added to the reaction system at the same time: DMABP0.0906g (4wt.%, relative to the initial St weight) and PMA0.1ml (4vol.%, relative to the initial St volume). SEM and TEM observed that the obtained microspheres were dumbbell-shaped polymer microspheres with a part of the surface rough and uniformly cross-linked, and another part with a smooth surface and a core-shell (cross-linked) structure (see Figure 2a).

Example 11

Others as in Example 1, two crosslinking agents were added to the reaction system at the same time: DMABP0.068g (3wt.%, relative to the initial St weight) and PGA0.075ml (3vol.%, relative to the initial St volume). SEM and TEM observed that the obtained microspheres were dumbbell-shaped polymer microspheres with a part of the surface rough and uniformly cross-linked, and another part with a smooth surface and a core-shell (cross-linked) structure (see Figure 2a).

Example 12

Others as in Example 1, two crosslinking agents were added to the reaction system at the same time: DMABP0.1133g (5wt.%, relative to the initial St weight) and PMA0.125ml (5vol.%, relative to the initial St volume). SEM and TEM observations showed that part of the surface was raspberry-shaped (many obvious small protrusions appeared) and uniformly cross-linked, while the other part had a smooth surface and a dumbbell-shaped polymer microsphere with a core-shell (cross-linked) structure ( See accompanying drawing 2b).

Example 13

Others as in Example 1, two crosslinking agents were added to the reaction system at the same time: DMABP0.0906g (4wt.%, relative to the initial St weight) and PGA0.1ml (4vol.%, relative to the initial St volume). SEM and TEM observations showed that part of the surface was raspberry-shaped (many obvious small protrusions appeared) and uniformly cross-linked, while the other part had a smooth surface and a dumbbell-shaped polymer microsphere with a core-shell (cross-linked) structure ( See accompanying drawing 2b).

Example 14

Others were as in Example 1, and two crosslinking agents were added to the reaction system at the same time: DMABP0.0227g (1wt.%, relative to the initial St weight) and PMA0.025ml (1vol.%, relative to the initial St volume). SEM and TEM observed that the obtained microspheres were polymer microspheres with a smooth surface and a core (non-crosslinked)-shell (dense crosslinked) structure (see Figure 4b).

Example 15

Others are as in Example 1, adding two kinds of crosslinking agents to the reaction system at the same time: DMABP0.0906g (4wt.%, relative to the initial St weight) and OTD0.01ml (4vol.%, relative to the initial St volume), to obtain a part of the surface Rough (multiple obvious small protrusions appear), internally crosslinked, while the other part has a smooth surface and no internally crosslinked snowman-shaped polymer microspheres (see Figure 1d).

Example 16

Others are as in Example 1, 0.0906g (4wt.%, relative to the initial St weight) of the crosslinking agent DMABP and 0.15ml (6vol.%, relative to the initial St volume) of the functional monomer GMA are added to the reaction system at the same time. SEM and TEM observed that the obtained microspheres were a part of the dumbbell-shaped polymer microspheres with rough surface (small dot protrusions, containing epoxy groups) and internal crosslinking, while the other part had a smooth surface and no internal crosslinking (see accompanying drawing 2c ).

Example 17

Others, as in Example 1, add crosslinking agent DMA-Fluo0.1812g (8wt.%, relative to the initial St weight) and functional monomer acrylic acid 0.025ml (AA, 1%, relative to the initial St volume) to the reaction system at the same time . SEM and TEM observed that the obtained microspheres were dumbbell-shaped polymer microspheres with a rough surface (with multiple obvious protrusions and carboxyl groups) and crosslinking, while the other part was smooth and non-crosslinked (see Figure 2d).

Example 18

Others were as in Example 1, and 0.0906 g of crosslinking agent DMABP (4wt.%, relative to the initial St weight) and functional monomer methacrylic acid (MAA, 2%, relative to the initial St volume) were added to the reaction system at the same time. SEM and TEM observed that the obtained microspheres were dumbbell-shaped polymer microspheres with a rough surface (with multiple obvious protrusions and carboxyl groups) and crosslinking, while the other part was smooth and non-crosslinked (see Figure 2d).

Example 19

Others are as in Example 1, and 0.0906 g of cross-linking agent DMABP (4wt.%, relative to the initial St weight) and functional monomer NIPAM (4%, relative to the initial St volume) are added to the reaction system at the same time. SEM and TEM observed that the obtained microspheres were snowman-shaped polymer microspheres with a rough surface (containing N-isopropyl group) and internal crosslinking, and another part with a smooth surface and no internal crosslinking (see Figure 1a).

Example 20

Others are as in Example 1, replaced by adding cross-linking agent DMABP0.0906g (4wt.%, relative to the initial St weight) and functional monomer 4-VP (4%, relative to the initial St volume) to the reaction system at the same time. The obtained microspheres observed by SEM and TEM are snowman-like polymer microspheres with a rough surface (multiple obvious small protrusions appearing, containing pyridyl groups) and cross-linking, and another part with a smooth surface and no cross-linking (see Figure 1d).

Example 21

Others are as in Example 1, adding 0.0906 g of cross-linking agent DMABP (4wt.%, relative to the initial St weight) and monomer PGA (4%, relative to the initial St volume) to the reaction system. SEM and TEM observations showed that one part of the surface was slightly rough and cross-linked, and the other part was smooth and non-cross-linked snowman-like polymer microspheres (see Figure 1f).

Example 22

Others are as in Example 1, and 0.0906 g of cross-linking agent DMABP (4wt.%, relative to the initial St weight) and monomer propargyl bromide (PBR, 4 vol.%, relative to the initial St volume) are added to the reaction system at the same time. SEM and TEM observations showed that one part of the surface was slightly rough and cross-linked, and the other part was smooth and non-cross-linked snowman-like polymer microspheres (see Figure 1f).

Example 23

Others, as in Example 1, add crosslinking agent DMABP0.0906g (4wt.%, relative to the initial St weight) and monomer propargyl bromoisobutyrate (PGBB, 3%, relative to the initial St volume). SEM and TEM observations showed that one part of the surface was slightly rough and cross-linked, and the other part was smooth and non-cross-linked snowman-like polymer microspheres (see Figure 1f).

Example 24

Others, as in Example 1, are replaced by adding crosslinking agent DMABP0.0906g (4wt.%, relative to the initial St weight) and monomer PGA (4%, relative to the initial St volume) to the reaction system, sodium styrene sulfonate NaSS. .0227g (1wt.%, relative to the weight of St), the initiator azobisisobutyronitrile AIBN0.0227g (1wt.%, relative to the weight of St). SEM and TEM observations showed that one part of the surface was slightly rough and cross-linked, and the other part was smooth and non-cross-linked snowman-like polymer microspheres (see Figure 1f).

Example 25

Others are as in Example 1, except that the cross-linking agent DMABP is replaced with PEGDA575, and the dosage is 0.25ml (10vol.%). The obtained microspheres observed by SEM and TEM are raspberry-like polymer microspheres with a flower-like surface and a gradient cross-linked interior (see Figure 3a).

Example 26

Others are as in Example 1, except that the cross-linking agent DMABP is replaced by PEGDA700, and the dosage is 0.25ml (10vol.%). The obtained microspheres observed by SEM and TEM are raspberry-like polymer microspheres with a flower-like surface and a gradient cross-linked interior (see Figure 3a).

Example 27

Others are as in Example 1, except that the cross-linking agent DMABP is replaced by PEGDA575, and the dosage is 0.1 ml (4 vol.%). The obtained microspheres observed by SEM and TEM are polymer microspheres with a rough surface and a core (sparsely cross-linked)-shell (densely cross-linked) structure (see Figure 4c).

Example 28

Others are as in Example 1, except that the cross-linking agent DMABP is replaced by PEGDA700, and the dosage is 0.1 ml (4 vol.%). The obtained microspheres observed by SEM and TEM are polymer microspheres with a rough surface and a core (non-crosslinked)-shell (dense crosslinked) structure (see Figure 4d).

Example 29

Others are as in Example 1, except that the cross-linking agent DMABP is replaced by the cross-linking agent TMPTA containing three double bonds. The obtained microspheres observed by SEM and TEM are rough and cross-linked polymer microspheres (see Figure 3b).

Example 30

Others are as embodiment 1, just change cross-linking agent DMABP into PMA, the consumption of PMA can be 1%. SEM and TEM observed that the obtained microspheres were core (non-crosslinked)-shell (dense crosslinked) polymer microspheres with smooth surface (see Figure 4b).

Example 31

Others are as embodiment 1, just change cross-linking agent DMABP into PMA, the consumption of PMA can be 20%. SEM and TEM observed that the obtained microspheres were core (non-crosslinked)-shell (dense crosslinked) polymer microspheres with smooth surface (see Figure 4b).

Example 32

Others are as in Example 1, except that the cross-linking agent DMABP is replaced by PGA, and the PGA consumption is 4%. SEM and TEM observed that the obtained microspheres were rough-surfaced core (non-crosslinked)-shell (dense crosslinked) polymer microspheres (see Figure 4d).

Claims (9)

1. the method for monodisperse polymer micro-sphere of snowman, dumbbell, raspberry shape or nucleocapsid structure is prepared in a step dispersion polymerization, it is characterized in that, monomer styrene-St, Sodium styrene sulfonate-NaSS, initiator Diisopropyl azodicarboxylate-AIBN and linking agent are stirred, are dissolved in forming reactions liquid in the mixed solution of organic solvent and water; Reacting liquid temperature is risen to 75 DEG C to start to react certain hour, obtain the monodisperse polymer micro-sphere of snowman's shape or dumb-bell shape or raspberry shape or nucleocapsid structure; Crosslinkers monomers A or three end group of described linking agent to be two end groups be double bond to be a crosslinkers monomers B or end group double bond of double bond and connection agent monomer C or two end group of an end group triple bond be in the crosslinkers monomers D of triple bond one or more.

2. the method for monodisperse polymer micro-sphere of snowman, dumbbell, raspberry shape or nucleocapsid structure is prepared according to a step dispersion polymerization of claim 1, it is characterized in that, also add function monomer in above-mentioned reaction solution, the consumption of functional group monomer is the 1-6wt.% of St consumption.

3. the method for monodisperse polymer micro-sphere of snowman, dumbbell, raspberry shape or nucleocapsid structure is prepared according to a step dispersion polymerization of claim 1, it is characterized in that, the reactor being furnished with agitator and reflux condensate device is placed in water bath with thermostatic control, add the mixed solution of organic solvent and water, then add monomer St, NaSS, initiator A IBN and linking agent, stir forming reactions liquid; Reacting liquid temperature is risen to 75 DEG C, reaction 8h; By final dispersion liquid centrifugation, topple over removing supernatant liquor, then add methanol wash, centrifugation, repeatable operation like this at least 3 times, obtains powdered sample, is dried to constant weight.

4. the method for monodisperse polymer micro-sphere of snowman, dumbbell, raspberry shape or nucleocapsid structure is prepared according to a step dispersion polymerization of claim 3, it is characterized in that, while adding monomer St, NaSS, initiator A IBN and linking agent, also add function monomer, described functional monomer is preferably selected from following monomer: containing epoxy based monomers, carboxyl group-containing monomer, amide containing class monomer, containing pyridyl monomer.

5. the method for monodisperse polymer micro-sphere of snowman, dumbbell, raspberry shape or nucleocapsid structure is prepared according to a step dispersion polymerization of claim 1, it is characterized in that, in the mixed solution of organic solvent used and water, organic solvent is selected from one or more in ethylene glycol, ethanol, methyl alcohol, and organic solvent accounts for the 60-80% of the mixed solution cumulative volume of organic solvent and water.

6. prepare the method for monodisperse polymer micro-sphere of snowman, dumbbell, raspberry shape or nucleocapsid structure according to a step dispersion polymerization of claim 1, it is characterized in that, the concentration of monomer St used is the consumption of 8 ~ 15wt.%, NaSS is the 1 ~ 4wt.% of St; The consumption of initiator used is the 1-3wt.% of St.

7. prepare the method for monodisperse polymer micro-sphere of snowman, dumbbell, raspberry shape or nucleocapsid structure according to a step dispersion polymerization of claim 1, it is characterized in that, linking agent A is the monomer containing two double bonds, and its chemical structure is as follows:

Wherein: R ₁, R ₂for H or CH ₃; R ₃for containing benzophenone unit fluorescein unit or oxyethyl group-CH ₂-CH ₂the structure of-O-unit;

Or linking agent A is: 4,4'-dimethacryloxy benzophenone-DMABP:

Or 4,4'-dimethacryloxy fluorescein-DMA-Fluo:

Or polyethyleneglycol diacrylate-PEGDA:

Crosslinking agent B is acrylic ester monomer Viscoat 295-TMPTA:

Linking agent C is propargylacrylate-PGA: or methacrylic acid alkynes propyl ester-PMA:

Linking agent D is the pungent diine of 1,7--OTD:

8. prepare the method for monodisperse polymer micro-sphere of snowman, dumbbell, raspberry shape or nucleocapsid structure according to a step dispersion polymerization of claim 1, it is characterized in that, the consumption of linking agent is the 1 ~ 20wt.% of St.

9. prepare the method for monodisperse polymer micro-sphere of snowman, dumbbell, raspberry shape or nucleocapsid structure according to a step dispersion polymerization of claim 2 or 7, it is characterized in that,

Be used alone the A linking agent containing benzophenone or fluorescein modular construction, obtain a part of surface irregularity, internal crosslinking, and another part smooth surface, inner not crosslinked snowman's shaped polymer microballoon; Or it is all smooth to obtain two portions surface, a part is crosslinked, and snowman's shaped polymer microballoon that another part is not cross-linked; Or obtain rough, the internal crosslinking in part surface, and another part smooth surface, internal portion are crosslinked, neck has multiple pimple, benzophenone or fluorescein modular construction snowman's shaped polymer pockety microballoon; Or obtain rough, the internal crosslinking in part surface, another part smooth surface, inner not crosslinked snowman's shaped polymer microballoon; Or obtain sparse and outside crosslinked closely knit, the ganoid nuclear-structure polymer shell microballoon of internal crosslinking;

When being used together with C linking agent PGA or PMA by the A linking agent containing benzophenone or fluorescein modular construction, obtain surface irregularity, internal portion be cross-linked, be partly the class snowman shaped polymer microballoon of nucleocapsid structure; Or obtain a part of surface irregularity and homogeneous cross-link and another part surface is more smooth and have the dumb-bell shape polymer microballoon of nucleocapsid structure; Or obtain part surface in raspberry shape and homogeneous cross-link another part surface more smooth and there is the dumb-bell shape polymer microballoon of nucleocapsid structure; Or obtain smooth surface, there is the polymer microballoon of nucleocapsid structure;

When being used together with D linking agent OTD by the A linking agent containing benzophenone or fluorescein modular construction, obtain rough, the internal crosslinking in part surface, and another part smooth surface, inner not crosslinked snowman's shaped polymer microballoon;

When being used together with difference in functionality monomer by the A linking agent containing benzophenone or fluorescein modular construction, increase the surface properties of particle in polymerization process, degree of swelling is different, the structure of resulting polymers microballoon, pattern and functional group present position are different; With containing when using together with epoxy based monomers, obtain a part of surface irregularity and crosslinked and another part smooth surface and crosslinked dumb-bell shape polymer microballoon; When using together with carboxyl group-containing monomer, obtain a part of surface irregularity and crosslinked and another part smooth surface and crosslinked dumb-bell shape polymer microballoon; Add in system together with amide containing class monomer, obtain a part of surface irregularity, be cross-linked, and another part smooth surface, not crosslinked snowman's shaped polymer microballoon; With containing adding together with pyridyl monomer, obtain part surface rough, crosslinked, another part smooth surface, not crosslinked snowman's shaped polymer microballoon; In time using together with alkynyl monomers, because this type of monomer not easily reacts, play solvent action, increase when particle is separated and be easily expressed into the new jut formed, finally obtain that a part of surface is slightly coarse, internal crosslinking, another part smooth surface, inner not crosslinked snowman's shaped polymer microballoon;

When being used alone the A linking agent containing oxyethyl group, obtain surface in flower-shaped, inner raspberry shaped polymer microballoon crosslinked in gradient through a step dispersion polymerization; Or obtain the polymer microballoon that surface is more coarse, have nucleocapsid structure; Or obtain surface irregularity, there is the polymer microballoon of nucleocapsid structure;

When being used alone B linking agent as TMPTA, obtain the polymer microballoon that particle surface is coarse, crosslinked;

When being used alone C linking agent, because double bond in linking agent is different with the reactive behavior of triple bond, obtain ganoid core-shell polymer microsphere; Or obtain shaggy core-shell polymer microsphere.