CN114653314A - Method for preparing self-assembled microcapsule - Google Patents

Abstract

The invention discloses a method for preparing self-assembled microcapsules, which comprises the following steps: dissolving a surfactant in deionized water, weighing a polymerized monomer, and dissolving an initiator in the deionized water; The active agent solution and the monomer mixture are cyclically transported to the supergravity rotating packed bed, and mixed to obtain a pre-emulsion; the initiator solution is added to the pre-emulsion to carry out the polymerization reaction. After the reaction is completed, the impurities are removed by dialysis to obtain colloidal particle water. Dispersion; the mixture of colloidal particle water dispersion, oil phase and emulsifier is circulated into a supergravity rotating packed bed to strengthen the emulsification process to obtain an emulsion; the emulsion is heated, centrifuged, washed and dried to obtain microcapsules. The colloidal particles prepared by the invention have small particle size and uniform distribution, and are 10-200 nm; the polymerization reaction time can be shortened by 20-50%; ‑10µm.

Description

A kind of method for preparing self-assembled microcapsules

technical field

The invention relates to the technical field of microcapsule preparation; more particularly, to a method for preparing self-assembled microcapsules.

Background technique

Microcapsules refer to solid particulate products that use natural or synthetic polymer materials as capsule wall materials and can embed solids, liquids or gases inside. The unique core-shell structure of the microcapsule enables it to protect the core material from escaping to the outside world, nor being affected by the intrusion of the external environment. According to the release characteristics of different wall materials to the core material, on the premise of retaining the original characteristics of the core material, it can realize its slow release, instant release or long-lasting preservation, so as to achieve the purpose of controlling the release of the core material. At present, the preparation and embedding technology of microcapsules has been widely used in the fields of medicine, food and textile.

Alexander F.Routh.Fabricationof colloidosomes at low temperature for the encapsulation ofthermallysensitive compounds[J].Journal ofColloid and Interface Science,2008,317:121–129.)。Keen等人^[8]利用Pickering乳液制备的自组装型微胶囊，包埋了淀粉酶、乳酸菌、酵母菌等大分子物质，既限制了被包埋物的活动，又可以在微胶囊内外进行小分子物质交换([8]Polly H R Keen.Encapsulation of biological material in colloidosomes[D].London:University of Cambridge,2013.)。上述制备的自组装型微胶囊的孔隙率和缓释速率均可调控，制备过程相对简单且生物毒性低。At the beginning of the 20th century, Ramsden ^[1] and Pickering ^[2] first reported the self-assembly process of colloidal particles at the oil-water interface to form stable Pickering emulsions ([1] Ramsden W. Separation of solids in the surface-layers of solutions and “suspensions” (observations on surface-membranes, bubbles, emulsions, and mechanical coagulation): Preliminary account[J].Proceedings of the Royal Society of London,1903,72:156–164;[2]Pickering SU.Emulsions[J] . Journal of the Chemical Society, Transactions, 1907, 91:2001-2021.). In the 1990s, Velev et al. ^[3-5 ] used Pickering emulsions to prepare self-assembled microcapsules, and the colloidal particles of the shell were fixed by the deposition of polyelectrolytes ([3] Velev OD, Furusawa K, Nagayama K. Assembly oflatex particles by using emulsion droplets astemplates.1.microstructured hollow spheres[J].Langmuir,1996,12:2374–2384;[4]Velev OD,Furusawa K,Nagayama K.Assembly of latex particles by using emulsion droplets as templates.2 .ball-like and composite aggregates[J].Langmuir,1996,12:2385–2391;[5]Velev OD,Nagayama K.Assembly oflatex particles by usingemulsion droplets.3.reverse(water in oil)system[J]. Langmuir, 1997, 13:1856–1859). Subsequently, Dinsmore et al. ^[6] invented a method of heating and fixing the shell of microcapsules, which heated the colloidal particles above the glass transition temperature to melt and cross-link the polymer colloidal particles together to form self-assembled microcapsules ([6] ] Dinsmore AD, Hsu MF, Nikolaides MG, Marquez M, Bausch AR, Weitz DA. Colloidosomes: selectively permeable capsules composed of colloidal particles [J]. Science, 2002, 298:1006-1009.). Routh et al. ^[7] further invented a method for preparing self-assembled microcapsules at low temperature. By controlling the heating temperature and heating time, the degree of melting and crosslinking of the colloidal particles in the shell layer of the microcapsules can be changed to achieve different sustained release rates. ([7]Samia

Alexander F. Routh. Fabrication of colloidosomes at low temperature for the encapsulation of thermallysensitive compounds [J]. Journal of Colloid and Interface Science, 2008, 317: 121–129.). Keen et al. ^[8] used the self-assembled microcapsules prepared by Pickering emulsion to embed macromolecular substances such as amylase, lactic acid bacteria, yeast, etc., which not only limited the activity of the embedded substances, but also carried out microcapsules inside and outside the microcapsules. Molecular material exchange ([8] Polly HR Keen. Encapsulation of biological material in colloidosomes [D]. London: University of Cambridge, 2013.). The porosity and sustained release rate of the self-assembled microcapsules prepared above can be adjusted, the preparation process is relatively simple, and the biological toxicity is low.

However, the current microcapsule preparation methods still have the following problems: 1) the preparation efficiency of the capsule wall material is low; 2) the particle size of the capsule wall material is not uniform; 3) the embedded material cannot be effectively controlled to release; 4) the microcapsule product Stability is not high.

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is to provide a method for preparing self-assembled microcapsules. The method can obtain a stable pre-emulsion of surfactant aqueous solution and monomer in the stage of capsule wall material, can control the particle size of colloidal particles, and greatly shorten the reaction time of the polymerization reaction; in the subsequent stage of preparing microcapsules, The formed water-in-oil Pickering emulsion is also more stable, and the particle size of the prepared microcapsules is smaller and more uniform. Different small molecular substances are embedded to achieve the effect of different sustained release rates; the microcapsules prepared by this method are in regular spherical shape, and the particle diameter is 0.1-10 μm.

In order to solve the above-mentioned technical problems, the present invention adopts the following technical scheme:

A method for preparing self-assembled microcapsules, comprising the steps of:

1) Dissolving the surfactant in deionized water to obtain a surfactant solution; weighing the polymerized monomers to obtain a monomer mixture; dissolving the initiator in deionized water to obtain an initiator solution;

2) Under a nitrogen atmosphere, the surfactant solution and the monomer mixture are cyclically transported into the supergravity rotating packed bed, and mixed to obtain a pre-emulsion;

3) adding the initiator solution to the pre-emulsion, carrying out a polymerization reaction, and after the reaction finishes, removing impurities by dialysis to obtain a colloidal particle water dispersion as a capsule wall material;

4) circulating the mixture of colloidal particle water dispersion, oil phase and emulsifier into the supergravity rotating packed bed to strengthen the emulsification process to obtain microemulsion or nanoemulsion;

5) heating the above-mentioned emulsion, centrifuging, washing with deionized water, dispersing in water to obtain water-phase microcapsules, or directly drying after washing to obtain microcapsule solid particles.

According to some embodiments of the present invention, in step 1), the surfactant is selected from one or more of the following substances: sodium dodecyl sulfonate, sodium dodecyl sulfate, polyvinyl alcohol, Polyethylene oxide, ammonium salts (eg lauryl ammonium chloride), quaternary ammonium salts (eg cetyltrimethylammonium bromide).

According to some embodiments of the present invention, in step 1), the amount of the surfactant is 0.1-8wt% of the total mass of the monomer; more preferably, the amount of the surfactant is 0.5% of the total mass of the monomer -5wt%.

According to some embodiments of the present invention, in step 1), the polymerized monomer is selected from one or more of the following substances: styrene, butyl acrylate, methacrylic acid, acrylic acid, methyl methacrylate, Butyl methacrylate, dimethyl methacrylate, dimethylaminoethyl methacrylate, acrylamine hydrochloride, acrylamide, n-butyl cyanoacrylate, isopropylacrylamide, vinylpyridine.

According to some embodiments of the present invention, in step 1), the initiator is selected from one or more of the following substances: potassium persulfate, ammonium persulfate, sodium persulfate, hydrogen peroxide, azobisulfite Butylamidine hydrochloride, azodiisobutylimidazoline hydrochloride, azodiisopropylimidazoline.

According to some embodiments of the present invention, in step 1), the amount of the initiator is 0.1-5wt% of the total mass of the monomer; more preferably, the amount of the initiator is 0.5-3.5% of the total mass of the monomer wt%.

According to some embodiments of the present invention, in step 2), the cycle time of the mixture is 5-150min; more preferably, the cycle time of the mixture is 5-120min.

According to some embodiments of the present invention, in step 2), the rotating speed of the rotor of the supergravity rotating packed bed is 300-5000 rpm; more preferably, the rotating speed of the rotor is 500-2500 rpm. The rotor speed is adjusted by a frequency modulation variator.

According to some embodiments of the present invention, in step 3), the polymerization reaction temperature is 60-95°C, and the polymerization reaction time is 0.5-10 h; more preferably, the polymerization reaction temperature is 70-90°C, and the polymerization reaction time is 1-5h.

According to some embodiments of the present invention, in step 3), the initiator solution is added to the pre-emulsified solution to carry out the polymerization reaction, and the supergravity rotating packed bed is kept in circulation during the process;

According to some embodiments of the present invention, in step 3), the particle size of the colloidal particles is 10-200 nm, and the glass transition temperature of the colloidal particles can be adjusted according to the ratio of the polymerized monomers. The colloidal polymer particles are spherical and dispersed in Good dispersibility in water.

According to some embodiments of the present invention, in step 4), the solid content of the aqueous dispersion of colloidal particles is 0.5-5 wt%.

According to certain embodiments of the present invention, in step 4), the oil phase is selected from one or more of the following substances: sunflower oil, soybean oil, peanut oil, isohexadecane, isoamyl acetate, meat Isopropyl myristate, castor oil, perilla oil, olive oil, palm oil.

According to certain embodiments of the present invention, in step 4), the emulsifier is selected from one or more of the following substances: polyglycerol-3-polyricinoleate, sorbitan oleate, Sucrose polystearate, diglycerol polypropylene glycol ether, polyoxyethylene oleate, lecithin.

According to some embodiments of the present invention, in step 4), the volume dosage ratio of the colloidal particle water dispersion, the oil phase and the emulsifier is 1:100:1-2.5.

According to certain embodiments of the present invention, in step 4), the emulsification process time is 5-120 min; more preferably, the emulsification process time is 5-90 min.

According to some embodiments of the present invention, in step 5), the heating temperature is 20-60° C., and the heating time is 1-30 min.

Any range recited herein includes the endpoints and any number between the endpoints and any sub-ranges formed by the endpoints or any number between the endpoints.

Unless otherwise specified, each raw material in the present invention can be obtained through commercial purchase, and the equipment used in the present invention can be performed with conventional equipment in the field or with reference to the prior art in the field.

Compared with the prior art, the present invention has the following beneficial effects:

1) The colloidal particles prepared by the present invention have a small particle size and a uniform distribution, ranging from 10 to 200 nm, whose glass transition temperature can be adjusted, and the polymerization reaction time is greatly shortened;

2) The present invention can flexibly control the size and porosity of the microcapsules through changes in the particle size of the colloidal particles, changes in the heating temperature of the emulsion, and changes in the heating time of the emulsion, so as to achieve the effects of different sustained release rates;

3) The self-assembled microcapsules prepared by the present invention have good sphericity, the polymer nanoparticles are densely and regularly arranged on the surface of the microcapsules, and ≥90% of the microcapsules are regular spherical, and the particle size is between 0.1-10 μm;

4) The preparation method of the microcapsules of the present invention has higher yield, low cost, low biological toxicity, simple operation and easy industrial production.

Description of drawings

The specific embodiments of the present invention will be described in further detail below in conjunction with the accompanying drawings.

Fig. 1 is the scanning electron microscope image of obtained capsule wall material colloidal particles in Example 1;

Fig. 2 is the scanning electron microscope picture of the self-assembled microcapsule obtained when the rotating packed bed rotating speed is 500rpm in embodiment 1;

Fig. 3 is the scanning electron microscope image of the self-assembled microcapsule obtained when the rotating packed bed rotating speed is 1000rpm in Example 1;

Fig. 4 is the scanning electron microscope picture of the self-assembled microcapsule obtained when the rotating packed bed rotational speed is 1500rpm in embodiment 1;

Fig. 5 is the scanning electron microscope picture of the self-assembled microcapsule obtained when the rotating packed bed rotational speed is 2500rpm in embodiment 1;

6 is a confocal microscope image of the microcapsules embedded with allura red dye in Example 2;

Fig. 7 is the scanning electron microscope image of the self-assembled microcapsule prepared in Comparative Example 1;

8 is a scanning electron microscope image of the self-assembled microcapsules prepared in Comparative Example 3;

FIG. 9 is a scanning electron microscope image of the colloidal particles prepared in Comparative Example 5. FIG.

FIG. 10 is a scanning electron microscope image of the colloidal particles prepared in Comparative Example 8. FIG.

Detailed ways

In order to illustrate the present invention more clearly, the present invention will be further described below with reference to the preferred embodiments. Those skilled in the art should understand that the content specifically described below is illustrative rather than restrictive, and should not limit the protection scope of the present invention.

As an aspect of the present invention, a method for preparing self-assembled microcapsules, comprising the steps of:

1) Dissolving the surfactant in deionized water to obtain a surfactant solution; weighing the polymerized monomers to obtain a monomer mixture; dissolving the initiator in deionized water to obtain an initiator solution;

2) Under a nitrogen atmosphere, the surfactant solution and the monomer mixture are cyclically transported into the supergravity rotating packed bed, and mixed to obtain a pre-emulsion;

3) adding the initiator solution to the pre-emulsion, carrying out a polymerization reaction, and after the reaction finishes, removing impurities by dialysis to obtain a colloidal particle water dispersion as a capsule wall material;

4) circulating the mixture of colloidal particle water dispersion, oil phase and emulsifier into the supergravity rotating packed bed to strengthen the emulsification process to obtain microemulsion or nanoemulsion;

5) heating the above-mentioned emulsion, centrifuging, washing with deionized water, dispersing in water to obtain water-phase microcapsules, or directly drying after washing to obtain microcapsule solid particles.

In certain embodiments, in step 1), the surfactant is selected from one or more of the following: sodium dodecyl sulfonate, sodium dodecyl sulfate, polyvinyl alcohol, polycyclic Ethylene oxide, ammonium salts (eg lauryl ammonium chloride), quaternary ammonium salts (eg cetyltrimethylammonium bromide). The presence of surfactant reduces the oil-water interfacial tension, disperses the monomer into fine droplets, and forms a protective layer on the surface of the droplets to stabilize the pre-emulsion; other surfactant raw materials have poor emulsification effect and are difficult to degrade.

In certain embodiments, in step 1), the amount of the surfactant is 0.1-8wt% of the total mass of the monomer; more preferably, the amount of the surfactant is 0.5-5wt% of the total mass of the monomer %. Outside the range of this dosage, the emulsification effect will not be achieved at least; more will easily lead to serious foaming during the reaction process, serious adhesion of the prepared colloidal particles, and difficulty in cleaning the surfactant.

In certain embodiments, in step 1), the polymerized monomer is selected from one or more of the following: styrene, butyl acrylate, methacrylic acid, acrylic acid, methyl methacrylate, methyl methacrylate Butyl acrylate, dimethyl methacrylate, dimethylaminoethyl methacrylate, acrylamine hydrochloride, acrylamide, n-butyl cyanoacrylate, isopropylacrylamide, vinylpyridine. Selecting other polymerized monomer raw materials is not suitable as the capsule wall material, the self-assembly behavior in the emulsion is poor, the morphology of the prepared microcapsules is poor, and the yield is too low.

In certain embodiments, in step 1), the initiator is selected from one or more of the following substances: potassium persulfate, ammonium persulfate, sodium persulfate, hydrogen peroxide, azodiisobutyl Amidine hydrochloride, azodiisobutylimidazoline hydrochloride, azodiisopropylimidazoline. Other initiator raw materials have higher decomposition temperature and lower decomposition rate.

In some embodiments, in step 1), the amount of the initiator is 0.1-5wt% of the total mass of the monomer; more preferably, the amount of the initiator is 0.5-3.5wt% of the total mass of the monomer . Outside this dosage range, if the amount is less, it is not easy to initiate, and the reaction cannot be carried out normally;

In certain embodiments, in step 2), the cycle time of the mixture is 5-150min; more preferably, the cycle time of the mixture is 5-120min. Outside this time range, if it is low, a stable pre-emulsion will not be formed; if it is high, impurities will increase and the machine will be seriously damaged.

In certain embodiments, in step 2), the rotating speed of the rotor of the supergravity rotating packed bed is 300-5000 rpm; more preferably, the rotating speed of the rotor is 500-2500 rpm, or 1000-2500 rpm. The rotor speed is adjusted by a frequency modulation variator. Outside this speed range, if the speed is low, the mixing effect will be general, and the formed droplets will be large and non-uniform; if the speed is high, the impurities will increase and the machine loss will be serious.

In certain embodiments, in step 3), the polymerization reaction temperature is 60-95°C, and the polymerization reaction time is 0.5-10 h; more preferably, the polymerization reaction temperature is 70-90°C, and the polymerization reaction time is 1- 5h. Outside this temperature range, if the temperature is low, the reaction rate will be extremely slow; if the temperature is high, the reaction rate will be extremely fast, which is difficult to control, and the product dispersibility will be poor. Deterioration of appearance.

In some embodiments, in step 3), the particle size of the colloidal particles is 10-200 nm, the glass transition temperature of the colloidal particles can be adjusted according to the ratio of the polymerized monomers, and the colloidal polymer particles are spherical, dispersed in water and Good dispersibility.

In certain embodiments, in step 4), the solid content of the colloidal particle aqueous dispersion is 0.5-5 wt%. Outside the range of the dosage, if the amount is too small, the material of the capsule wall will be insufficient, and the yield of microcapsules will be low;

In certain embodiments, in step 4), the oil phase is selected from one or more of the following: sunflower oil, soybean oil, peanut oil, isohexadecane, isoamyl acetate, myristic acid Isopropyl ester, castor oil, perilla oil, olive oil, palm oil. In water-in-oil Pickering emulsions, the oil phase acts as the continuous phase. Other oil phase raw materials have high biological toxicity and high cost.

In certain embodiments, in step 4), the emulsifier is selected from one or more of the following substances: polyglycerol-3-polyricinoleate, sorbitan oleate, sucrose poly Stearate, Diglycerol Polypropylene Glycol Ether, Polyoxyethylene Oleate, Lecithin. After adding an emulsifier to the oil-water system, water and oil can be mixed with each other to form a completely dispersed emulsion. Selecting other emulsifier raw materials has poor emulsification effect and is difficult to clean.

In certain embodiments, in step 4), the volume and dosage ratio of the colloidal particle water dispersion, the oil phase and the emulsifier is 1:100:1-2.5.

In certain embodiments, in step 4), the emulsification process time is 5-120min; more preferably, the emulsification process time is 5-90min. Outside this time range, if it is low, a stable emulsion will not be formed; if it is high, impurities will increase and the machine will be seriously damaged.

In some embodiments, in step 5), the heating temperature is 20-60° C., and the heating time is 1-30 min. Outside this temperature range, if the temperature is low, the colloidal particles cannot be melted and microcapsules cannot be prepared. The melting degree of colloidal particles is extremely high, and the porosity of microcapsules is extremely low; outside this time range, if the temperature is low, the colloidal particles are not completely melted, and if the temperature is high, there is no significant change in long-term heating.

Example 1

A kind of method for preparing self-assembled microcapsules

Dissolve 0.4 g of sodium lauryl sulfate in 180 mL of deionized water; mix 30 g of methyl methacrylate, 9.6 g of butyl acrylate and 0.4 g of acrylic acid monomers; turn on the supergravity rotating device, and adjust the rotational speed to 1500 rpm; The feed pump is used to transport the surfactant solution and the monomer mixture together into the rotating packed bed, and circulate for 60 minutes to obtain a pre-emulsion. Dissolve 0.4 g of potassium persulfate in 20 mL of deionized water, and add it to the pre-emulsion to initiate a polymerization reaction. The reaction temperature is controlled at 85 °C, and the reaction time is 2 h. During the reaction process, it has been under a nitrogen atmosphere and turned on for 3 ℃ circulating condensed water. The prepared colloidal particle aqueous dispersion is divided into dialysis bags for dialysis, and impurities such as unreacted monomers and emulsifiers are removed, and the desired capsule wall material is obtained after one week. Figure 1 is a scanning electron microscope image of the synthesized colloidal particles, with a particle size of about 59 nm.

Deionized water was added to adjust the solid content of the aqueous dispersion of colloidal particles to 2 wt%. Take 2mL of it and mix it with 200mL of sunflower oil and 5mL of sorbitan oleate, divide the mixture into four parts, transport it to the rotating packed bed for mixing and strengthening, and adjust the rotating speed of the rotating packed bed to be 500rpm, 1000rpm, 1500rpm and 2500rpm respectively. , cycle 60min. The resulting emulsion was heated in a 48°C water bath for 15 min. After centrifugation and washing with deionized water, self-assembled microcapsules dispersed in water were obtained.

Figure 2 is a scanning electron microscope image of the microcapsules prepared by rotating the packed bed at 500 rpm. Under this condition, the amount of sorbitan oleate is too much, it is difficult to wash, and the microcapsules have irregular morphology. Fig. 3 is a scanning electron microscope image of the microcapsules prepared by rotating the packed bed at a speed of 1000 rpm. Most of the microcapsules prepared under this condition are regular spherical, and the surface is slightly wrinkled. Figure 4 is a scanning electron microscope image of the microcapsules prepared by rotating the packed bed at a speed of 1500 rpm. Under this condition, the colloidal particles on the surface of the microcapsules are regularly arranged and the morphology is good. Figure 5 is a scanning electron microscope image of the microcapsules prepared by rotating the packed bed at a rotational speed of 2500 rpm. Under this condition, the microcapsules are in a regular spherical shape, and the surface colloidal particles have a high degree of melting.

Example 2

A kind of method for preparing self-assembled microcapsule-embedded allura red dye

Dissolve 0.8 g of sodium lauryl sulfate in 180 mL of deionized water; mix different monomer ratios of methyl methacrylate:butyl acrylate:acrylic acid=65:34:1, 75:24:1, 85:14 :1 monomer mixture, the total mass of the monomer mixture is 40g; turn on the supergravity rotating device, adjust the speed to 1500rpm; turn on the feed pump, transport the surfactant solution and the monomer mixture to the rotating packed bed together, circulate 60min to obtain a pre-emulsion. Dissolve 0.8 g of potassium persulfate in 20 mL of deionized water, and add it to the pre-emulsion to initiate a polymerization reaction. The reaction temperature is controlled at 85 °C, and the reaction time is 2 h. During the reaction process, it has been under a nitrogen atmosphere and turned on for 3 ℃ circulating condensed water. The prepared colloidal particle aqueous dispersion is divided into dialysis bags for dialysis, and impurities such as unreacted monomers and emulsifiers are removed, and the desired capsule wall material is obtained after one week.

Using the glass transition temperature of the monomer homopolymer, as shown in formula (1) according to the Fox equation, the glass transition temperature Tg of the polymer can be calculated.

In the formula, w ₁ , 2, 3...n is the mass fraction of monomers 1, 2, 3...n, Tg ₁ , 2, 3...n is the Tg of the homopolymer of monomers 1, 2, 3...n, The unit is K. The actual glass transition temperature of the polymer was determined by differential scanning calorimetry. Table 1 shows the glass transition temperature of colloidal particles prepared with different monomer ratios. It can be seen that the theoretical calculated value is very close to the actual measured value.

Table 1: Glass transition temperature of colloidal particles prepared with different monomer ratios

Deionized water was added to adjust the solid content of the aqueous dispersion of colloidal particles to 2 wt%. 0.04 g of allura red was weighed and dissolved in 2 mL of the above-mentioned colloidal particle aqueous dispersion. The above-mentioned mixture of dissolving allura red was mixed with 200 mL of sunflower oil and 5 mL of sorbitan oleate, and transported to a rotating packed bed for mixing and strengthening. The resulting emulsion was heated in a 48°C water bath for 15 min. After centrifugation and washing with deionized water, self-assembled microcapsules dispersed in water were obtained.

Figure 6 is a confocal microscope image of the microcapsules embedded with allura red dye, from which it can be seen that the dye was successfully embedded.

Example 3

A kind of method for preparing self-assembled microcapsules embedded doxorubicin hydrochloride

Dissolve 1.0 g of sodium dodecyl sulfonate in 180 mL of deionized water; mix 25.6 g of styrene, 14 g of butyl acrylate and 0.4 g of acrylic acid monomers; turn on the supergravity rotating device, and adjust the speed to 1500 rpm; turn on the feed pump , the surfactant solution and the monomer mixture are transported to the rotating packed bed together, and circulated for 30 minutes to obtain a pre-emulsion. Dissolve 1.0 g of ammonium persulfate in 20 mL of deionized water, and add it to the pre-emulsion to initiate a polymerization reaction. The reaction temperature is controlled at 80 °C, and the reaction time is 4 h. During the reaction process, it has been under a nitrogen atmosphere and turned on for 3 ℃ circulating condensed water. The prepared colloidal particle aqueous dispersion is divided into dialysis bags for dialysis, and impurities such as unreacted monomers and emulsifiers are removed, and the desired capsule wall material is obtained after one week.

Deionized water was added to adjust the solid content of the aqueous dispersion of colloidal particles to 2 wt%. 0.04 g of doxorubicin hydrochloride was weighed and dissolved in 2 mL of the above-mentioned colloidal particle aqueous dispersion. The above-mentioned mixture of dissolving doxorubicin hydrochloride was mixed with 200 mL of sunflower oil and 5 mL of sucrose polystearate, and transported to a rotating packed bed for mixing and strengthening. The resulting emulsion was heated in a 48°C water bath for 30 min. After centrifugation, washing with deionized water, and drying, the solid particles of self-assembled microcapsules are obtained.

Example 4

A kind of method for preparing self-assembled microcapsules

Dissolve 0.4 g of polyvinyl alcohol in 180 mL of deionized water; mix 6.4 g of styrene, 3.5 g of butyl methacrylate, and 0.1 g of acrylic acid; turn on the supergravity rotating device, and adjust the speed to 800 rpm; turn on the feed pump, The surfactant solution and the monomer mixture were transported into the rotating packed bed together, and circulated for 10 minutes to obtain a pre-emulsion. Dissolve 0.4 g of azodiisopropyl imidazoline in 20 mL of deionized water, and add it to the pre-emulsion to initiate the polymerization reaction. The reaction temperature is controlled at 70 ° C, the reaction time is 10 h, and the reaction process is always in nitrogen. Under the atmosphere and turn on the circulating condensed water at 3 ℃. The prepared colloidal particle aqueous dispersion is divided into dialysis bags for dialysis, and impurities such as unreacted monomers and emulsifiers are removed, and the desired capsule wall material is obtained after one week.

Deionized water was added to adjust the solid content of the colloidal particle aqueous dispersion to 0.5 wt%. Take 2mL and 200mL of perilla oil, mix with 3mL, 4mL, and 5mL of sorbitan oleate, respectively, and transfer the mixture to the rotating packed bed for mixing and strengthening, adjust the rotating speed of the rotating packed bed to be 1500rpm respectively, and circulate for 45min. . The resulting emulsion was heated in a 48°C water bath for 15 min. After centrifugation and washing with deionized water, self-assembled microcapsules dispersed in water were obtained.

Example 5

A kind of method for preparing self-assembled microcapsules

Dissolve 0.4 g of dodecyl ammonium chloride in 180 mL of deionized water; mix 6.4 g of acrylamide, 33.2 g of dimethyl methacrylate, and 0.4 g of acrylic acid monomers; turn on the supergravity rotating device, and adjust the speed to 800rpm; turn on the feed pump, transport the surfactant solution and the monomer mixture together into the rotating packed bed, and circulate for 60min to obtain a pre-emulsion. Dissolve 0.4 g of azodiisopropyl imidazoline in 20 mL of deionized water, and add it to the pre-emulsion to initiate the polymerization reaction. The reaction temperature is controlled at 70 ° C, the reaction time is 4 h, and the reaction process is always in nitrogen. Under the atmosphere and turn on the circulating condensed water at 3 °C. The prepared colloidal particle aqueous dispersion is divided into dialysis bags for dialysis, and impurities such as unfinished monomers and emulsifiers are removed, and the desired capsule wall material is obtained after one week.

Deionized water was added to adjust the solid content of the colloidal particle aqueous dispersion to 4 wt%. Take 2 mL of it and mix it with 200 mL of olive oil and 5 mL of lecithin, transfer the mixture to a rotating packed bed for mixing and strengthening, adjust the rotational speed of the rotating packed bed to 1500 rpm, and circulate for 30 min. The obtained emulsion was divided into four parts and heated for 15 min in a water bath at 40°C, 44°C, 52°C, and 56°C, respectively. After centrifugation and washing with deionized water, self-assembled microcapsules dispersed in water were obtained. As the heating temperature of the emulsion increases, the degree of melting of the colloidal particles on the surface of the microcapsules increases, and the porosity of the microcapsules decreases.

Comparative Example 1

Example 1 was repeated: the only difference was that deionized water was added to adjust the solid content of the colloidal particle aqueous dispersion to 5.6 wt%, the yield of the microcapsule product of this comparative example was less than 50%, and there were still many non-self-assembled microcapsules. Scatter colloidal particles. The SEM image of the microcapsules prepared with the dispersion solid content of 5.6 wt% is shown in Fig. 7 .

Comparative Example 2

Repeat Example 1: the only difference is that adding deionized water to adjust the solid content of the colloidal particle aqueous dispersion to 0.4wt%, the yield of the microcapsule product of this comparative example is less than 20%, and the addition amount of the capsule wall material is too small .

Comparative Example 3

Repeat Example 1: the difference is only that the emulsifier sorbitan oleate is 6mL, the dosage is too much, it is difficult to wash, and most of the prepared microcapsule products are not regular spherical, and the scanning electron microscope image is as shown in Figure 8 shown.

Comparative Example 4

Repeat Example 1: the only difference is that the emulsifier sorbitan oleate is 1 mL, the dosage is too small, it is difficult to form a stable Pickering emulsion, and the yield of the prepared microcapsule product is extremely low.

Comparative Example 5

Example 1 was repeated: the only difference was that the amount of the surfactant sodium lauryl sulfate was 1.6 g, that is, 4 wt % of the total monomer mass, the prepared colloidal particles had poor morphology and poor dispersibility. The scanning electron microscope image of the product is shown in Figure 9.

Comparative Example 6

Repeat Example 1: the only difference is that the total mass of the monomer is 5 g, the solid content of the prepared colloidal particle aqueous dispersion is too low, and the subsequent preparation of microcapsules requires a complicated concentration process.

Comparative Example 7

Example 1 was repeated: the only difference was that the mixing cycle time of the pre-emulsification process was 150 min, too much impurities entered the sample, and the solid content of the prepared colloidal particle aqueous dispersion was too low.

Comparative Example 8

Example 1 was repeated: the only difference was that in the process of preparing the capsule wall material, the supergravity rotating packed bed was not used, and the polymerization reaction was carried out in a traditional stirred tank. The polymerization reaction ended at 4 h, and the reaction could not be completed within 2 h, and the prepared colloidal particles had a large particle size and a wide particle size distribution range. The scanning electron microscope image is shown in Figure 10.

Obviously, the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those of ordinary skill in the art, changes or modifications in other different forms can also be made on the basis of the above description. Not all implementations can be exhaustive here. Any obvious changes or changes derived from the technical solutions of the present invention are still within the protection scope of the present invention.

Claims (10)

1. A method for preparing self-assembled microcapsules, comprising the steps of:

1) dissolving a surfactant in deionized water to obtain a surfactant solution; weighing the polymerization monomers to obtain a monomer mixture; dissolving an initiator in deionized water to obtain an initiator solution;

2) under the nitrogen atmosphere, circularly conveying the surfactant solution and the monomer mixture to a supergravity rotating packed bed, and mixing to obtain a pre-emulsion;

3) adding an initiator solution into the pre-emulsion to perform polymerization reaction, and dialyzing to remove impurities after the reaction is finished to obtain a colloidal particle water dispersion serving as a capsule wall material;

4) circularly introducing the mixture of the colloidal particle aqueous dispersion, the oil phase and the emulsifier into a supergravity rotating packed bed to strengthen the emulsification process to obtain microemulsion or nano emulsion;

5) heating the emulsion, centrifuging, washing with deionized water, dispersing in water to obtain water phase microcapsule, or washing and directly drying to obtain microcapsule solid particles.

2. The method for preparing self-assembled microcapsules according to claim 1, characterized in that: in step 1), the surfactant is selected from one or more of the following substances: sodium dodecyl sulfate, polyvinyl alcohol, polyethylene oxide, ammonium salt and quaternary ammonium salt.

3. The process for preparing self-assembling microcapsules according to claim 1, wherein: in the step 1), the dosage of the surfactant is 0.1-8 wt% of the total mass of the monomers; more preferably, the surfactant is used in an amount of 0.5 to 5 wt% based on the total mass of the monomers.

4. The process for preparing self-assembling microcapsules according to claim 1, wherein: in step 1), the polymerized monomer is selected from one or more of the following substances: styrene, butyl acrylate, methacrylic acid, acrylic acid, methyl methacrylate, butyl methacrylate, dimethyl methacrylate, dimethylaminoethyl methacrylate, allylamine hydrochloride, acrylamide, n-butyl cyanoacrylate, isopropylacrylamide, vinylpyridine.

5. The process for preparing self-assembling microcapsules according to claim 1, wherein: in step 1), the initiator is selected from one or more of the following substances: potassium persulfate, ammonium persulfate, sodium persulfate, hydrogen peroxide, azobisisobutylamidine hydrochloride, azobisisobutylimidazoline hydrochloride, and azobisisopropylimidazoline.

6. The process for preparing self-assembling microcapsules according to claim 1, wherein: in the step 1), the using amount of the initiator is 0.1-5 wt% of the total mass of the monomers; more preferably, the initiator is used in an amount of 0.5 to 3.5 wt% based on the total mass of the monomers.

7. The process for preparing self-assembling microcapsules according to claim 1, wherein: in the step 2), the circulation time of the mixture is 5-150 min; more preferably, the mixture cycle time is from 5 to 120 min;

preferably, in the step 2), the rotating speed of the rotor of the supergravity rotating packed bed is 300-5000 rpm; more preferably, the rotor speed is 500-.

8. The process for preparing self-assembling microcapsules according to claim 1, wherein: in the step 3), the polymerization reaction temperature is 60-95 ℃, and the polymerization reaction time is 0.5-10 h; more preferably, the polymerization temperature is 70-90 ℃ and the polymerization time is 1-5 h;

preferably, in the step 3), the initiator solution is added into the pre-emulsified solution to carry out polymerization reaction, and the circulating operation of the super-gravity rotating packed bed is kept in the process;

preferably, in the step 3), the particle size of the colloidal particles is 10-200 nm.

9. The process for preparing self-assembling microcapsules according to claim 1, wherein: in step 4), the solid content of the aqueous colloidal particle dispersion is 0.5 to 5 wt%;

preferably, in step 4), the oil phase is selected from one or more of the following: sunflower seed oil, soybean oil, peanut oil, isohexadecane, isoamyl acetate, isopropyl myristate, castor oil, perilla oil, olive oil and palm oil;

preferably, in step 4), the emulsifier is selected from one or more of the following: polyglycerol-3-polyricinoleate, sorbitan oleate, sucrose polystearate, diglycerol polypropylene glycol ether, polyoxyethylene oleate and lecithin;

preferably, in the step 4), the volume using ratio of the colloidal particle water dispersion, the oil phase and the emulsifier is 1:100: 1-2.5;

preferably, in the step 4), the emulsifying process time is 5-120 min; more preferably, the emulsification process time is 5-90 min.

10. The method for preparing self-assembled microcapsules according to claim 1, characterized in that: in the step 5), the heating temperature is 20-60 ℃, and the heating time is 1-30 min.

Images