CN112679658B - Water-insoluble temperature and pH dual-sensitive microgel and preparation method thereof - Google Patents

Water-insoluble temperature and pH dual-sensitive microgel and preparation method thereof Download PDF

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CN112679658B
CN112679658B CN202011565941.1A CN202011565941A CN112679658B CN 112679658 B CN112679658 B CN 112679658B CN 202011565941 A CN202011565941 A CN 202011565941A CN 112679658 B CN112679658 B CN 112679658B
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孙亚娟
齐佳悦
吕妍
杨成
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Jiangnan University
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Abstract

The invention discloses a water-insoluble temperature pH dual-sensitive microgel and a preparation method thereof, wherein the preparation method comprises the steps of dissolving a temperature-sensitive hydrogel monomer, a pH-sensitive hydrogel monomer and a cross-linking agent in water to obtain an aqueous phase solution; adding an initiator solution into the aqueous phase solution to obtain a mixed solution; dissolving a high molecular polymer in an oil phase, and introducing nitrogen into the solution to remove oxygen to obtain an oil phase solution; adding the mixed solution into the oil phase solution, and shearing and mixing to obtain an emulsion; and (3) crosslinking the emulsion by ultraviolet irradiation, washing, and freeze-drying. According to the invention, the ethyl cellulose film is attached to the surface layer of the microgel, so that the prepared microgel has water insolubility, the slow release effect of the microgel is greatly improved, and the application of the microgel in an oily environment is realized.

Description

Water-insoluble temperature and pH dual-sensitive microgel and preparation method thereof
Technical Field
The invention belongs to the technical field of daily chemical industry, and particularly relates to a water-insoluble temperature and pH dual-sensitive microgel and a preparation method thereof.
Background
The hydrogel is a natural hydrophilic high polymer, is generally crosslinked by physical or chemical behaviors to form a three-dimensional network structure, and has extremely strong swelling performance in water. The gel is mainly divided into two types, one type is an environment-responsive gel, and hydrophilic and hydrophobic changes can be generated according to changes of external temperature, pH, electromagnetism and the like; one is an environmentally non-responsive hydrogel that does not significantly change in response to external changes. The environmental responsive gel has attracted wide attention due to its special properties, wherein the microgel stimulated by both temperature and pH can be used as a medium for interaction between biological tissues and the external environment due to its special properties, and becomes a hotspot of research in recent years, and is often used in the fields of drug loading, medicine, biosensing, catalysis, and the like. At present, the preparation methods mainly adopted by the temperature/pH dual-stimulation intelligent microgel comprise soap-free emulsion polymerization, emulsion polymerization and precipitation polymerization. Most polymerization processes usually incorporate metallic elements or halides, which limits the use of the products in biological applications.
The sustained-release microcapsule usually uses a material with sustained-release property as a wall material, and a core material is wrapped by adopting a microencapsulation technology so as to achieve the purpose of slowing down the release of the core material. Among them, ethyl cellulose is often used as a wall material in microcapsules because of its porous and sustained-release skeleton structure. The microcapsule has better slow release performance, thereby improving the utilization rate of the medicine.
The main research direction of the existing microcapsules lies in that two or more stimuli-responsive microgels under different conditions are prepared by copolymerizing one or more temperature, pH and ion-sensitive gels or modifying monomers. However, most of the prepared microgel is water-soluble, and the preparation of oil-soluble multi-response microgel is not reported at present, so that the drug encapsulation condition is limited, the release rate is high, and a large space for improvement is left in biological application and drug encapsulation performance.
Disclosure of Invention
This section is for the purpose of summarizing some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. In this section, as well as in the abstract and the title of the invention of this application, simplifications or omissions may be made to avoid obscuring the purpose of the section, the abstract and the title, and such simplifications or omissions are not intended to limit the scope of the invention.
The present invention has been made keeping in mind the above and/or other problems occurring in the prior art.
Therefore, the invention overcomes the defects in the prior art, and provides the water-insoluble temperature and pH dual-sensitive microgel and the preparation method thereof, so that the prepared microgel has water insolubility, the slow release effect of the microgel is greatly improved, and the application of the microgel in an oily environment is greatly improved.
In order to solve the technical problems, the invention provides the following technical scheme: a method for preparing water-insoluble temperature and pH dual-sensitive microgel comprises,
dissolving a temperature-sensitive hydrogel monomer, a pH-sensitive hydrogel monomer and a cross-linking agent in water to obtain an aqueous phase solution;
adding an initiator solution into the aqueous phase solution to obtain a mixed solution;
dissolving a high molecular polymer in an oil phase, and introducing nitrogen into the solution to remove oxygen to obtain an oil phase solution;
adding the mixed solution into the oil phase solution, and shearing and mixing to obtain an emulsion;
and (3) crosslinking the emulsion by ultraviolet irradiation, washing, and freeze-drying to obtain the water-insoluble temperature and pH dual-sensitive microgel.
As a preferable embodiment of the method for preparing the water-insoluble temperature pH dual sensitive microgel of the invention, wherein: in the aqueous phase solution, the mass fraction of the temperature-sensitive hydrogel monomer is 2-40 mas%, the mass fraction of the pH-sensitive hydrogel monomer is 5-50 mas%, and the mass fraction of the crosslinking agent is 0.1-5 mas%.
As a preferable embodiment of the method for preparing the water-insoluble temperature pH dual sensitive microgel of the invention, wherein: in the oil phase solution, the mass fraction of the high molecular polymer is 0.5-10 mas%.
As a preferable embodiment of the method for preparing the water-insoluble temperature pH dual sensitive microgel of the invention, wherein: the initiator solution is obtained by dissolving an initiator monomer in water, wherein the mass fraction of the initiator monomer is 0.1-5 mas%.
As a preferable embodiment of the method for preparing the water-insoluble temperature pH dual sensitive microgel of the invention, wherein: adding the water phase solution into the oil phase solution, wherein the volume ratio of the oil phase solution to the water phase solution is 0.5-10: 1.
As a preferable embodiment of the method for preparing the water-insoluble temperature pH dual sensitive microgel of the invention, wherein: and shearing and mixing for 1-5 min at 5000-10000 rpm.
As a preferable embodiment of the method for preparing the water-insoluble temperature pH dual sensitive microgel of the invention, wherein: and carrying out ultraviolet irradiation crosslinking, wherein the irradiation time is 5-40 min.
As a preferable embodiment of the method for preparing the water-insoluble temperature pH dual sensitive microgel of the invention, wherein: and washing for 1-5 times by using ethanol.
Another object of the present invention is to provide a water-insoluble temperature pH dual sensitive microgel prepared by the method for preparing the water-insoluble temperature pH dual sensitive microgel described in any one of the above.
As a preferred embodiment of the water-insoluble temperature pH dual sensitive microgel of the present invention, wherein: the temperature-sensitive hydrogel monomer comprises one or more of N-isopropylacrylamide, glycol, chitosan and xanthan gum;
the pH-sensitive hydrogel monomer comprises one or more of methacrylic acid, acrylic acid and dimethylaminoethyl methacrylate;
the cross-linking agent comprises one or more of N, N-methylene bisacrylamide and ethylene glycol dimethacrylate;
the oil phase comprises one or more of 2-octyl dodecanol, liquid paraffin, squalane, caprylic capric triglyceride;
the high molecular polymer comprises one or more of cellulose, chitin, amylopectin and ethyl cellulose;
the initiator comprises one or more of benzophenone, azodiisobutyramidine hydrochloride and benzoin ethyl ether.
Compared with the prior art, the invention has the following beneficial effects: according to the invention, a temperature-sensitive gel and a pH-sensitive gel are copolymerized, a temperature/pH double-sensitive microgel is prepared by means of photo-initiated polymerization and emulsion polymerization, and an ethyl cellulose film is attached to the surface layer of the microgel without adding other surfactants, so that the prepared microgel has water insolubility, the slow release effect of the microgel is greatly improved, and the application of the microgel in an oily environment is greatly improved. In addition, the obtained microgel slow release effect can be regulated and controlled in a wide range and high efficiency by means of conditions such as the mass fraction of the aqueous phase, the washing times of the microgel and the like, and is expected to be applied to biological slow release and other cosmetics products with special properties.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without inventive exercise. Wherein:
FIG. 1 is a graph showing the particle size distribution of microgel prepared in example 2 under different temperature conditions.
FIG. 2 is a graph showing the particle size distribution of microgel prepared in example 2 under different pH conditions.
FIG. 3 is the result of the encapsulated release of microgel prepared in example 2 under different pH conditions.
FIG. 4 is an optical microscope observation of the appearance of the crosslinked emulsion; wherein (a) is an optical microscope observation image obtained by dispersing the emulsion in ethanol after the emulsion is cured prepared in example 1; (b) an optical microscope observation image was obtained by dispersing the emulsion in ethanol after the emulsion was cured, prepared for example 2; (c) an optical microscope observation image obtained by dispersing the emulsion in ethanol after the emulsion was cured was prepared for example 3.
FIG. 5 is an appearance diagram of the microcapsule observed by a scanning electron microscope; wherein (a) is the appearance of the microcapsule prepared in example 1; (b) is an appearance diagram of the microcapsules prepared in example 2; (c) is an appearance diagram of the microcapsules prepared in example 3.
FIG. 6 is a graph showing the results of measuring the optical contact angle of microgel; wherein (a) is a graph of the measurement result of the optical contact angle of the microgel prepared in example 1; (b) is a graph of the results of optical contact angle measurements of the microgel prepared in example 2; (c) is a graph showing the results of measuring the optical contact angle of the microgel prepared in example 3.
FIG. 7 is a graph comparing the release results of microcapsules prepared with different washing times.
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention more comprehensible, specific embodiments thereof are described in detail below with reference to examples of the specification.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.
Furthermore, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
Example 1
(1) Placing a temperature-sensitive hydrogel monomer N-isopropyl acrylamide with the mass fraction of 10%, a pH-sensitive hydrogel monomer dimethylaminoethyl methacrylate with the mass fraction of 5% and a cross-linking agent N, N-methylene-bisacrylamide with the mass fraction of 2% in deionized water, and vortexing until the temperature-sensitive hydrogel monomer N-isopropyl acrylamide, the pH-sensitive hydrogel monomer dimethylaminoethyl methacrylate and the cross-linking agent N, N-methylene-bisacrylamide are completely dissolved; in order to simulate the entrapment release experiment, a certain amount of coloring agent is added into the entrapment release experiment, specifically, a methyl blue coloring agent with the mass fraction of 5% is added, and then the mixture is swirled until the mixture is completely dissolved;
(2) putting ethyl cellulose with the mass fraction of 0.5 percent into an oil phase of 2-n-octyl-1-dodecanol, and heating and stirring until the ethyl cellulose is completely dissolved;
(3) placing initiator azo diisobutyl amidine hydrochloride with the mass fraction of 0.5% in deionized water, and swirling until the initiator azo diisobutyl amidine hydrochloride is completely dissolved;
(4) introducing nitrogen into the oil phase solvent obtained in the step (2) until oxygen is completely removed;
(5) adding the initiator solution obtained in the step (3) into the water phase solution obtained in the step (1), and swirling until the initiator solution is uniformly mixed;
(6) adding the mixed solution obtained in the step (5) into the oil phase solution obtained in the step (2) according to the oil-water ratio of 3:1, and shearing and mixing for 2min at 8000rpm by adopting an FM200 high-speed shearing machine to obtain emulsion;
(7) placing the emulsion obtained in the step (6) in an ultraviolet crosslinking instrument, and performing illumination crosslinking for 40 min;
(8) and (5) fully washing the microgel obtained in the step (7) by using ethanol for 2 times, and fully drying the microgel in a vacuum freezing drying agent to obtain a microgel sample 1.
Example 2
(1) Placing a temperature-sensitive hydrogel monomer N-isopropyl acrylamide with the mass fraction of 10%, a pH-sensitive hydrogel monomer dimethylaminoethyl methacrylate with the mass fraction of 5% and a cross-linking agent N, N-methylene-bisacrylamide with the mass fraction of 2% in deionized water, and vortexing until the temperature-sensitive hydrogel monomer N-isopropyl acrylamide, the pH-sensitive hydrogel monomer dimethylaminoethyl methacrylate and the cross-linking agent N, N-methylene-bisacrylamide are completely dissolved; in order to simulate the entrapment release experiment, a certain amount of coloring agent is added into the entrapment release experiment, specifically, a methyl blue coloring agent with the mass fraction of 5% is added, and then the mixture is swirled until the mixture is completely dissolved;
(2) putting 5% of ethyl cellulose in an oil phase of 2-n-octyl-1-dodecanol, and heating and stirring until the ethyl cellulose is completely dissolved;
(3) placing initiator azo diisobutyl amidine hydrochloride with the mass fraction of 0.5% in deionized water, and swirling until the initiator azo diisobutyl amidine hydrochloride is completely dissolved;
(4) introducing nitrogen into the oil phase solvent obtained in the step (2) until oxygen is completely removed;
(5) adding the initiator solution obtained in the step (3) into the water phase solution obtained in the step (1), and swirling until the initiator solution is uniformly mixed;
(6) adding the mixed solution obtained in the step (5) into the oil phase solution obtained in the step (2) according to the oil-water ratio of 3:1, and shearing and mixing for 2min at 8000rpm by adopting an FM200 high-speed shearing machine to obtain emulsion;
(7) placing the emulsion obtained in the step (6) in an ultraviolet crosslinking instrument, and performing illumination crosslinking for 40 min;
(8) and (5) fully washing the microgel obtained in the step (7) by using ethanol for 2 times, and fully drying the microgel in a vacuum freezing drying agent to obtain a microgel sample 2.
FIG. 1 is a graph showing the particle size distribution of microgel sample 2 at different temperatures; as can be seen from FIG. 1, the prepared microgel is temperature sensitive.
FIG. 2 is a graph showing the particle size distribution of microgel sample 2 at different pH conditions; as can be seen from fig. 2, the microgel prepared is pH sensitive.
The microgel sample 2 is subjected to a simulated entrapment release experiment, and the test method comprises the following steps: 1mg of the encapsulated lyophilized sample is dissolved in 1ml of PBS solution with different pH (the experiment is carried out under the conditions of pH 2, 7.4 and 10 respectively and the environment temperature is constant at 24 ℃), the lyophilized sample is put into a dialysis bag and placed in 99ml of PBS solution with the same pH environment for dialysis, magnetic stirring is kept, and 1ml of solution is taken at regular intervals and added back to 1ml of the same PBS solution. The absorbance was measured to calculate the cumulative release.
FIG. 3 shows the microgel loading release effect of microgel sample 2 under different pH conditions; as can be seen from fig. 3, the prepared microgel has pH sensitivity, and the pH difference affects the particle size of the microgel, which in turn affects the release effect.
Example 3
(1) Placing a temperature-sensitive hydrogel monomer N-isopropyl acrylamide with the mass fraction of 10%, a pH-sensitive hydrogel monomer dimethylaminoethyl methacrylate with the mass fraction of 5% and a cross-linking agent N, N-methylene-bisacrylamide with the mass fraction of 2% in deionized water, and vortexing until the temperature-sensitive hydrogel monomer N-isopropyl acrylamide, the pH-sensitive hydrogel monomer dimethylaminoethyl methacrylate and the cross-linking agent N, N-methylene-bisacrylamide are completely dissolved; in order to simulate the entrapment release experiment, a certain amount of coloring agent is added into the entrapment release experiment, specifically, a methyl blue coloring agent with the mass fraction of 5% is added, and then the mixture is swirled until the mixture is completely dissolved;
(2) putting 10% ethyl cellulose in the oil phase of 2-n-octyl-1-dodecanol, heating and stirring until the ethyl cellulose is completely dissolved;
(3) placing initiator azo diisobutyl amidine hydrochloride with the mass fraction of 0.5% in deionized water, and swirling until the initiator azo diisobutyl amidine hydrochloride is completely dissolved;
(4) introducing nitrogen into the oil phase solvent obtained in the step (2) until oxygen is completely removed;
(5) adding the initiator solution obtained in the step (3) into the water phase solution obtained in the step (1), and swirling until the initiator solution is uniformly mixed;
(6) adding the mixed solution obtained in the step (5) into the oil phase solution obtained in the step (2) according to the oil-water ratio of 3:1, and shearing and mixing for 2min at 8000rpm by adopting an FM200 high-speed shearing machine to obtain emulsion;
(7) placing the emulsion obtained in the step (6) in an ultraviolet crosslinking instrument, and performing illumination crosslinking for 40 min;
(8) and (4) fully washing the microgel obtained in the step (7) by using ethanol for 2 times, and fully drying the microgel in a vacuum freezing drying agent to obtain a microgel sample 3.
FIG. 4 is an optical microscope observation image obtained by dispersing an emulsion in ethanol after the emulsion is cured when ethyl cellulose with different mass fractions is added in examples 1 to 3. As can be seen from FIG. 4, the fine particles obtained in examples 1 to 3 using 0.5 to 10% of ethylcellulose show a decrease in the content of ethylcellulose, and when the content of ethylcellulose is too low, the particles are sticky and broken.
And (3) detection by a scanning electron microscope: the microgel particles were freeze-dried and placed on a silicon wafer, and the microgel particle morphology was observed by a field emission scanning electron microscope (FESEM, JSM 7401F, JEOL, Japan) after gold spraying, as shown in fig. 5. As can be seen from FIG. 5, the morphology of the particles prepared in examples 1 to 3 using 0.5 to 10% ethylcellulose varied greatly with the content of ethylcellulose. When the content of the ethyl cellulose is too low (0.5%), the shrinkage of the particles after freeze drying is obvious, the spherical appearance cannot be ensured, and even the particles are broken; when the ethyl cellulose content is too high (10%), the particles cannot be dispersed, the adhesion phenomenon is obvious, and even agglomeration occurs.
FIG. 6 is a graph showing the results of optical contact angle measurement on the resulting microgel. As can be seen from fig. 6, after the samples 1 to 3 were tabletted, the static contact angles thereof increased gradually with the increase of the content of the added ethylcellulose, which proves that the addition of the ethylcellulose can indeed render the prepared particles water-insoluble.
Example 4
(1) Placing a temperature-sensitive hydrogel monomer N-isopropyl acrylamide with the mass fraction of 10%, a pH-sensitive hydrogel monomer dimethylaminoethyl methacrylate with the mass fraction of 5% and a cross-linking agent N, N-methylene-bisacrylamide with the mass fraction of 2% in deionized water, and vortexing until the temperature-sensitive hydrogel monomer N-isopropyl acrylamide, the pH-sensitive hydrogel monomer dimethylaminoethyl methacrylate and the cross-linking agent N, N-methylene-bisacrylamide are completely dissolved; in order to simulate the entrapment release experiment, a certain amount of coloring agent is added into the entrapment release experiment, specifically, a methyl blue coloring agent with the mass fraction of 5% is added, and then the mixture is swirled until the mixture is completely dissolved;
(2) putting 5% of ethyl cellulose in an oil phase of 2-n-octyl-1-dodecanol, and heating and stirring until the ethyl cellulose is completely dissolved;
(3) placing initiator azo diisobutyl amidine hydrochloride with the mass fraction of 0.5% in deionized water, and swirling until the initiator azo diisobutyl amidine hydrochloride is completely dissolved;
(4) introducing nitrogen into the oil phase solvent obtained in the step (2) until oxygen is completely removed;
(5) adding the initiator solution obtained in the step (3) into the water phase solution obtained in the step (1), and swirling until the initiator solution is uniformly mixed;
(6) and (3) mixing the mixed solution obtained in the step (5) according to an oil-water ratio of 3:1, adding the mixture into the oil phase solution obtained in the step (2), and shearing and mixing the mixture for 2min at 8000rpm by using an FM200 high-speed shearing machine to obtain emulsion;
(7) placing the emulsion obtained in the step (6) in an ultraviolet crosslinking instrument, and performing illumination crosslinking for 40 min;
(8) and (4) fully washing the microcapsules obtained in the step (7) by ethanol for 1 time, and fully drying the microcapsules in a vacuum freezing drying agent to obtain a microcapsule sample 4.
Example 5
(1) Placing a temperature-sensitive hydrogel monomer N-isopropyl acrylamide with the mass fraction of 10%, a pH-sensitive hydrogel monomer dimethylaminoethyl methacrylate with the mass fraction of 5% and a cross-linking agent N, N-methylene-bisacrylamide with the mass fraction of 2% in deionized water, and vortexing until the temperature-sensitive hydrogel monomer N-isopropyl acrylamide, the pH-sensitive hydrogel monomer dimethylaminoethyl methacrylate and the cross-linking agent N, N-methylene-bisacrylamide are completely dissolved; in order to simulate the entrapment release experiment, a certain amount of coloring agent is added into the entrapment release experiment, specifically, a methyl blue coloring agent with the mass fraction of 5% is added, and then the mixture is swirled until the mixture is completely dissolved;
(2) putting 5% of ethyl cellulose in an oil phase of 2-n-octyl-1-dodecanol, and heating and stirring until the ethyl cellulose is completely dissolved;
(3) placing initiator azo diisobutyl amidine hydrochloride with the mass fraction of 0.5% in deionized water, and swirling until the initiator azo diisobutyl amidine hydrochloride is completely dissolved;
(4) introducing nitrogen into the oil phase solvent obtained in the step (2) until oxygen is completely removed;
(5) adding the initiator solution obtained in the step (3) into the water phase solution obtained in the step (1), and swirling until the initiator solution is uniformly mixed;
(6) and (3) mixing the mixed solution obtained in the step (5) according to an oil-water ratio of 3:1, adding the mixture into the oil phase solution obtained in the step (2), and shearing and mixing the mixture for 2min at 8000rpm by using an FM200 high-speed shearing machine to obtain emulsion;
(7) placing the emulsion obtained in the step (6) in an ultraviolet crosslinking instrument, and performing illumination crosslinking for 40 min;
(8) and (4) fully washing the microcapsules obtained in the step (7) by ethanol for 3 times, and fully drying the microcapsules in a vacuum freezing drying agent to obtain a microcapsule sample 5.
Example 6
(1) Placing a temperature-sensitive hydrogel monomer N-isopropyl acrylamide with the mass fraction of 10%, a pH-sensitive hydrogel monomer dimethylaminoethyl methacrylate with the mass fraction of 5% and a cross-linking agent N, N-methylene-bisacrylamide with the mass fraction of 2% in deionized water, and vortexing until the temperature-sensitive hydrogel monomer N-isopropyl acrylamide, the pH-sensitive hydrogel monomer dimethylaminoethyl methacrylate and the cross-linking agent N, N-methylene-bisacrylamide are completely dissolved; in order to simulate the entrapment release experiment, a certain amount of coloring agent is added into the entrapment release experiment, specifically, a methyl blue coloring agent with the mass fraction of 5% is added, and then the mixture is swirled until the mixture is completely dissolved;
(2) putting 5% of ethyl cellulose in an oil phase of 2-n-octyl-1-dodecanol, and heating and stirring until the ethyl cellulose is completely dissolved;
(3) placing initiator azo diisobutyl amidine hydrochloride with the mass fraction of 0.5% in deionized water, and swirling until the initiator azo diisobutyl amidine hydrochloride is completely dissolved;
(4) introducing nitrogen into the oil phase solvent obtained in the step (2) until oxygen is completely removed;
(5) adding the initiator solution obtained in the step (3) into the water phase solution obtained in the step (1), and swirling until the initiator solution is uniformly mixed;
(6) and (3) mixing the mixed solution obtained in the step (5) according to an oil-water ratio of 3:1, adding the mixture into the oil phase solution obtained in the step (2), and shearing and mixing the mixture for 2min at 8000rpm by using an FM200 high-speed shearing machine to obtain emulsion;
(7) placing the emulsion obtained in the step (6) in an ultraviolet crosslinking instrument, and performing illumination crosslinking for 40 min;
(8) and (4) fully washing the microcapsules obtained in the step (7) by ethanol for 4 times, and fully drying the microcapsules in a vacuum freezing drying agent to obtain a microcapsule sample 6.
The microgel samples 2, 4, 5 and 6 are subjected to simulated entrapment release experiments, and the test method comprises the following steps: dissolving 1mg of the carrier freeze-dried sample in 1ml of PBS solution with the pH value of 7.5, keeping the ambient temperature at 24 ℃, putting the sample into a dialysis bag, putting the dialysis bag into 99ml of PBS solution with the same pH environment for dialysis, keeping magnetic stirring, and taking 1ml of solution at regular intervals and adding back to 1ml of the same PBS solution. The absorbance was measured to calculate the cumulative release.
FIG. 7 shows the encapsulated release effect of microcapsules prepared from different numbers of washing of the microgel samples 2, 4, 5 and 6 with microcapsules. As can be seen from fig. 7, as the number of washing times increases, the encapsulated release effect of the microcapsules becomes faster, and the sustained release effect of the microgels can be adjusted by the number of washing times.
The invention obtains a water-insoluble temperature/pH dual sensitive microgel, which can respectively cause particle size change under the stimulation of temperature and pH, and ethyl cellulose replaces a surfactant in the process of preparing emulsion, is attached to the surface of a gel drop for stabilization through physical adsorption, and can also form a layer of hydrophobic film on the surface of the microgel to ensure that the microgel has water insolubility. Greatly improves the slow release effect of the microgel and the application thereof in an oily environment.
The invention provides a water-insoluble multi-responsiveness microgel obtained by copolymerizing a temperature-sensitive hydrogel monomer and a pH-sensitive hydrogel monomer, which has not been reported before. At the moment, the ethyl cellulose not only can play an emulsifying role, but also can be attached to the surface of the microgel to modify the surface of the microgel so as to obtain a hydrophobic layer, further enhance the slow release effect of the microgel and expand the utilization area of the microgel. In addition, the slow-release effect of the microgel can be adjusted by the number of washing times.
It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.

Claims (7)

1. A preparation method of water-insoluble temperature and pH dual-sensitive microgel is characterized by comprising the following steps: comprises the steps of (a) preparing a mixture of a plurality of raw materials,
dissolving a temperature-sensitive hydrogel monomer, a pH-sensitive hydrogel monomer and a cross-linking agent in water to obtain an aqueous phase solution; the temperature-sensitive hydrogel monomer is N-isopropyl acrylamide, the pH-sensitive hydrogel monomer is dimethylaminoethyl methacrylate, and the cross-linking agent is N, N-methylene bisacrylamide;
adding an initiator solution into the aqueous phase solution to obtain a mixed solution;
dissolving a high molecular polymer in an oil phase, and introducing nitrogen into the solution to remove oxygen to obtain an oil phase solution; in the oil phase solution, the mass fraction of the high molecular polymer is 5 mas%; the high molecular polymer is ethyl cellulose; the oil phase is 2-n-octyl-1-dodecanol;
adding the mixed solution into the oil phase solution, and shearing and mixing to obtain an emulsion;
and (3) crosslinking the emulsion by ultraviolet irradiation, washing, and freeze-drying to obtain the water-insoluble temperature and pH dual-sensitive microgel.
2. The method for preparing a water-insoluble temperature pH dual sensitive microgel of claim 1, wherein: in the aqueous phase solution, the mass fraction of the temperature-sensitive hydrogel monomer is 2-40 mas%, the mass fraction of the pH-sensitive hydrogel monomer is 5-50 mas%, and the mass fraction of the crosslinking agent is 0.1-5 mas%.
3. The method for preparing a water-insoluble temperature pH dual sensitive microgel of claim 1, wherein: the initiator solution is obtained by dissolving an initiator in water, wherein the mass fraction of the initiator is 0.1-5 mas%.
4. The method for preparing a water-insoluble temperature and pH dual sensitive microgel as claimed in any one of claims 1 to 3, wherein: and shearing and mixing for 1-5 min at 5000-10000 rpm.
5. The method for preparing a water-insoluble temperature pH dual sensitive microgel of claim 4, wherein: and carrying out ultraviolet irradiation crosslinking, wherein the irradiation time is 5-40 min.
6. The method for preparing a water-insoluble temperature and pH dual sensitive microgel as claimed in any one of claims 1 to 3 and 5, wherein: and washing for 1-5 times by using ethanol.
7. A water-insoluble temperature pH dual sensitive microgel is characterized in that: the water-insoluble temperature and pH dual-sensitive microgel is prepared by the preparation method of the water-insoluble temperature and pH dual-sensitive microgel as claimed in any one of claims 1 to 6.
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