A kind of reverse temperature-sensitive copolymer and preparation method thereof

Abstract

The present invention provides a reverse thermosensitive copolymer and a preparation method thereof, and relates to the technical field of thermosensitive materials. The reverse thermosensitive copolymer is prepared by mixing a hydrophilic monomer containing a double bond, a hydrophobic monomer containing a double bond, a cross-linking agent, a cosolvent, an initiator, a neutralizer, an emulsifier, etc., and then dispersing them in deionized water after polymerization and neutralization. The present invention overcomes the shortcomings of the prior art. The prepared reverse thermosensitive copolymer has the characteristics that as the temperature rises, the viscosity of the system increases to a semi-gel or gel state, and as the temperature further rises, it becomes a low-viscosity liquid. The temperature range in which it becomes a gel or semi-gel state is 15-50°C, and it can be applied to temperature-sensitive sensors, pH-responsive sensors, or temperature-sensitive intelligent response-type medical dressings, cosmetics and other fields.

Description

Technical Field

[0001] The invention relates to the technical field of temperature-sensitive materials, and in particular to a reverse temperature-sensitive copolymer and a preparation method thereof. Background Art

[0002] Environmental stimulus responsive polymers are polymers that can sense external stimuli such as pH, temperature, light, electric field, magnetic field, etc. and respond. Among them, temperature-responsive polymerization does not rely on other chemical additives, and the temperature response speed is fast and drastic. Therefore, it stands out among many environmental stimulus responsive polymers. In recent decades, the study of related structures (such as hydrogels, films, nanoparticles, polymer brushes, coatings) has become a research hotspot in the field of materials. Thermosensitive polymers can respond to temperature stimuli, and there is a phase transition temperature in their aqueous solutions, so that their hydrophilicity, volume, micelle structure, etc. will change significantly with changes in temperature. Due to the special temperature responsiveness of thermosensitive polymers, they have broad application prospects in biomedicine, genetic engineering, sensors, textile engineering, environmental engineering, aerospace and other fields.

[0003] Among these smart responsive polymers, thermosensitive reversible hydrogels can be used to maintain contact with the treatment site and can have the effect of controlled or sustained release of active ingredients over a long period of time. The reverse thermosensitive reversible gel of hydrogel seems to offer the best potential in this regard. The "reverse thermosensitive reversible hydrogel composition" disclosed in patent CN201610982443.4 discloses the phase transition process of the reverse thermosensitive reversible hydrogel system, that is, the so-called reverse thermosensitive reversible copolymer system, which is a substance whose solution viscosity increases with the increase of temperature and decreases with the decrease of temperature. The copolymer has a transition process from solution to gel state, and this process is that as the temperature rises, a low-viscosity solution is transformed into a high-viscosity gel form; when the temperature continues to rise, the copolymer system will undergo a process of transitioning from a gel state to a solution state. In this patent, polymers such as polyethylene oxide and polypropylene oxide are used to prepare a series of thermosensitive medical hydrogels under the action of gel adjuvants.

[0004] At present, the generally recognized mechanism of thermosensitive polymer transformation behavior is: thermosensitive polymers have both hydrophilic and hydrophobic groups. In aqueous solution, these groups will interact with water molecules. Temperature changes will cause a sharp change in the polymer's hydrophilic / hydrophobic balance, so that the thermosensitive polymer aqueous solution changes from a clear homogeneous phase to a turbid solid-liquid phase. The temperature corresponding to the phase transition is the phase transition temperature of the thermosensitive polymer. Similar products are often prepared using N-isopropylacrylamide as a functional monomer. The material selection is too single, and the existing phase transition temperature thermosensitive polymer materials have a weak response to the pH of the overall material, which limits the scope of use of reverse thermosensitive materials. Summary of the invention

[0005] In view of the shortcomings of the prior art, the present invention provides a reverse thermosensitive copolymer and a preparation method thereof, which is prepared by free radical polymerization of hydrophilic monomers and hydrophobic monomers, thereby expanding the selection range of raw materials for the preparation of reverse thermosensitive materials and facilitating actual production and processing. At the same time, the material has a certain pH response function, which effectively ensures the application range of the reverse thermosensitive copolymer.

[0006] To achieve the above objectives, the technical solution of the present invention is implemented through the following technical solutions:

[0007] A reverse thermosensitive copolymer, wherein the reverse thermosensitive copolymer is an aqueous dispersion prepared by mixing an effective solid substance with deionized water, and the effective solid content of the aqueous dispersion is 5-37%, and further preferably the effective solid content is 15-30%;

[0008] The effective solid material is prepared from the following raw materials in parts by weight: 3.8-13.9 parts of hydrophilic monomers containing double bonds, 5.2-20 parts of hydrophobic monomers containing double bonds, 0.01-1 parts of crosslinking agents, 2.8-6.5 parts of cosolvents, 0.06-1.1 parts of initiators, 2.3-6.8 parts of neutralizers, and 0-0.5 parts of emulsifiers.

[0009] Preferably, the hydrophilic monomer containing a double bond includes but is not limited to at least one of acrylic acid, methacrylic acid, acrylamide, itaconic acid, hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxyethyl methacrylate and hydroxypropyl methacrylate.

[0010] Preferably, the hydrophobic monomer containing a double bond includes, but is not limited to, at least two of methyl acrylate, ethyl acrylate, butyl acrylate, isooctyl acrylate, hexadecyl acrylate, octadecyl acrylate, eicosyl acrylate, methyl methacrylate, butyl methacrylate, octadecyl methacrylate, hexadecyl methacrylate, eicosyl methacrylate, styrene, acrylonitrile, methacrylonitrile, and vinyl acetate.

[0011] Preferably, the initiator is at least one of azobisisobutyronitrile, azobisisovaleronitrile, azobisisoheptanenitrile, benzoyl peroxide, dodecanoyl peroxide and the like.

[0012] Preferably, the cross-linking agent is at least one of divinylbenzene, ethylene glycol diacrylate, triethylene glycol diacrylate, polyethylene glycol diacrylate, pentaerythritol triacrylate, N,N-methylenebisacrylamide and the like.

[0013] Preferably, the neutralizing agent is at least one of triethanolamine, diethanolamine, dimethylethanolamine, N-methyldiethanolamine, N-ethyldiethanolamine, N-propyldiethanolamine, N-butyldiethanolamine, N,N-dimethylethanolamine, triethylamine, 2-amino-2-methylpropanol (AMP-95), aminopropanol, N-ethylmorpholine and the like.

[0014] Preferably, the co-solvent is at least one of ethanol, ethylene glycol, propylene glycol, butanol, ethylene glycol butyl ether, propylene glycol butyl ether, propylene glycol methyl ether acetate, dipropylene glycol methyl ether, dipropylene glycol dimethyl ether and the like.

[0015] The method for preparing the reverse temperature-sensitive copolymer comprises the following steps:

[0016] (1) fully mixing a hydrophilic monomer containing a double bond, a hydrophobic monomer containing a double bond, an initiator, and a cosolvent to obtain a prepolymer solution for use;

[0017] (2) taking 5-25% of the total amount of the prepolymer liquid in the above prepolymer liquid, heating it to 60-85° C. to initiate polymerization, and then dripping the remaining prepolymer liquid to carry out polymerization reaction. After the dripping is completed, the temperature is kept for 0.5-2 hours to obtain a polymer liquid;

[0018] (3) adding a neutralizing agent to the polymer solution in step (2) to carry out a neutralization reaction, and obtaining a neutralized solution for use;

[0019] (4) adding an emulsifier and deionized water to the neutralized solution in the above step (3) to disperse the solution, thereby obtaining a water dispersion which is a reverse temperature-sensitive copolymer.

[0020] The reverse temperature-sensitive copolymer can be applied to temperature-sensitive sensors, pH-responsive sensors, temperature-sensitive intelligent responsive medical dressings, cosmetics and other fields.

[0021] The present invention provides a reverse temperature-sensitive copolymer and a preparation method thereof, which has the advantages of:

[0022] (1) The reverse thermosensitive copolymer of the present invention is formed by free radical polymerization of hydrophilic monomers and hydrophobic monomers. As the temperature rises, the hydrogen bonds in the system are destroyed, the molecular motion is enhanced, a certain association is formed between the hydrophobic segments, and the molecular chains form a body state. From the surface observation, it is manifested as the viscosity of the system increasing to a gel state; as the temperature further rises, the association bonds are destroyed, the molecular chains in the system shrink, and the substance in the gel state will be transformed into a low-viscosity liquid. The temperature range for it to become a gel or semi-gel is 15 to 50°C; this reverse thermosensitive reversible hydrogel system can be used as a new type of auxiliary material for temperature-controlled viscosity change in products such as medicines and cosmetics; it can be widely used in the fields of local active ingredients for humans and animals, and has the advantages of convenient filling, easy and uniform application during use, and extended residence time; at the same time, the viscosity of this reverse thermosensitive copolymer is sensitive to temperature and can also be used as a temperature sensor.

[0023] (2) The copolymer prepared by the present invention uses acrylic acid and methacrylic acid monomers as raw materials, so that the polymer has both reverse temperature-sensitive properties and pH-responsive functions, further expanding the application range of the material.

[0024] (3) The thermosensitive copolymer prepared by the present invention is reversible in morphology. After repeated heating and cooling, it can still maintain stable thermosensitive performance and ensure the application effect of the material.

[0025] (4) The thermosensitive copolymer prepared by the present invention does not use polypropylene oxide-polyethylene oxide substances as raw materials, nor does it use commonly used N-isopropylacrylamide thermosensitive monomers; it mainly uses the change of hydrophilicity and hydrophobicity between hydrophilic monomers containing olefinic bonds and hydrophobic monomers containing olefinic bonds to prepare the thermosensitive hydrogel; wherein the monomers are derived from acrylic acid and acrylate, vinyl monomers, etc., and the selection range of raw materials is wide, which can be beneficial to the needs of different application scenarios. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 The viscosity of the thermosensitive copolymer prepared in Examples 1-6 of the present invention varies with temperature;

[0027] Figure 2 The viscosity of the thermosensitive copolymer prepared in Example 3 of the invention varies with pH. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention is clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0029] Embodiment 1:

[0030] Preparation of reverse thermosensitive copolymers:

[0031] (1) Accurately weigh 12 g of methacrylic acid, 8 g of acrylic acid, 4 g of hydroxyethyl acrylate, 18 g of methyl methacrylate, 20 g of styrene, 12 g of butyl methacrylate, 8 g of octadecyl methacrylate, 0.8 g of N,N-methylenebisacrylamide, 0.9 g of benzoyl peroxide, and 20 g of propylene glycol, and mix thoroughly to form a prepolymer solution;

[0032] (2) Add 10 g of prepolymer solution into the reaction bottle, heat to 75°C to initiate polymerization, and then drop the remaining prepolymer solution into the reaction bottle for further polymerization reaction. The dropping time is controlled to be 2.5 h. After the dropping is completed, keep warm for 1 h. Then add 20.3 g of triethanolamine for neutralization. Finally, add 220 g of deionized water into the reactor for dispersion to obtain a reverse thermosensitive copolymer.

[0033] Embodiment 2:

[0034] Preparation of reverse thermosensitive copolymers:

[0035] (1) accurately weighing 8 g of methacrylic acid, 20 g of acrylic acid, 2 g of itaconic acid, 20 g of butyl acrylate, 35 g of styrene, 16 g of acrylonitrile, 15 g of 2-ethylhexyl acrylate, 1.6 g of polyethylene glycol diacrylate, 0.8 g of azobisisobutyronitrile, and 30 g of propylene glycol methyl ether, and mixing them thoroughly to form a prepolymer solution;

[0036] (2) Add 16 g of prepolymer solution to the reaction bottle, heat to 80°C to initiate polymerization, and then drop the remaining prepolymer solution into the reaction bottle, controlling the dropping time to 3 hours; after the dropwise addition is completed, keep warm for 2 hours; then add 26 g of triethylamine for neutralization; finally, add 415 g of deionized water into the reactor for dispersion to obtain a reverse thermosensitive copolymer.

[0037] Embodiment 3:

[0038] Preparation of reverse thermosensitive copolymers:

[0039] (1) Accurately weigh 20 g of methacrylic acid, 6 g of hydroxypropyl acrylate, 16 g of methyl acrylate, 26 g of ethyl acrylate, 5 g of octadecyl acrylate, 5 g of vinyl acetate, 16 g of n-butyl acrylate, 2.0 g of divinylbenzene, 1.0 g of azobisisoheptanenitrile, and 10 g of ethylene glycol butyl ether, and mix thoroughly to obtain a prepolymer solution;

[0040] (2) Add 10 g of prepolymer solution to the reaction bottle, heat to 85°C to initiate polymerization, and then drop the remaining prepolymer solution into the reaction bottle, controlling the dropping time to 3.5 hours; after the dropwise addition is completed, keep warm for 0.5 hours; then, add 15 g of AMP-95 for neutralization and add 0.8 g of Tween 60; finally, add 210 g of deionized water into the reactor for dispersion to obtain a reverse thermosensitive copolymer.

[0041] Embodiment 4:

[0042] Preparation of reverse thermosensitive copolymers:

[0043] (1) Accurately weigh 23.8 g of methacrylic acid, 5.9 g of hydroxyethyl methacrylate, 5.3 g of acrylic acid, 16 g of methyl acrylate, 5 g of hexadecyl acrylate, 11 g of n-butyl acrylate, 3 g of ethylene glycol diacrylate, 1.1 g of azobisisoheptanenitrile, and 15 g of propylene glycol butyl ether, and mix thoroughly to obtain a prepolymer solution;

[0044] (2) 6 g of the prepolymer solution was added to a reaction bottle, heated to 68°C to initiate polymerization, and then the remaining prepolymer solution was dripped into the reaction bottle, and the dripping time was controlled to be 4.5 h; after the dripping was completed, it was kept warm for 2 h, and then 10 g of triethylamine and 10 g of N,N-dimethylethanolamine were added to neutralize the reaction; finally, 230 g of deionized water was added to the reactor for dispersion to obtain a reverse thermosensitive copolymer.

[0045] Embodiment 5:

[0046] Preparation of reverse thermosensitive copolymers:

[0047] (1) Accurately weigh 16 g of methacrylic acid, 12 g of acrylic acid, 6 g of hydroxyethyl methacrylate, 6 g of hydroxypropyl acrylate, 6 g of methyl acrylate, 16 g of butyl acrylate, 6 g of eicosyl acrylate, 0.5 g of divinylbenzene, 0.65 g of azobisisoheptanenitrile, and 25 g of propylene glycol methyl ether acetate, and mix thoroughly to obtain a prepolymer solution;

[0048] (2) Add 5 g of prepolymer solution to the reaction bottle, heat to 80°C to initiate polymerization, and then drop the remaining prepolymer solution into the reaction bottle, controlling the dropping time to be 2 h; after the dropwise addition is completed, keep warm for 1 h, then add 18 g of aminopropanol and 5.0 g (30% wt) of sodium hydroxide aqueous solution for neutralization; finally, add 380 g of deionized water into the reactor for dispersion to obtain a reverse thermosensitive copolymer.

[0049] Embodiment 6:

[0050] Preparation of reverse thermosensitive copolymers:

[0051] (1) Accurately weigh 6 g of methacrylic acid, 7 g of acrylic acid, 1 g of hydroxypropyl methacrylate, 15.2 g of ethyl acrylate, 18.8 g of butyl acrylate, 6.8 g of isooctyl acrylate, 6.5 g of octadecyl methacrylate, 13.5 g of methyl methacrylate, 4.2 g of acrylonitrile, 0.09 g of pentaerythritol triacrylate, 1.2 g of dodecyl peroxide, and 25 g of butanol, and mix thoroughly to obtain a prepolymer solution;

[0052] (2) Add 22 g of prepolymer solution to the reaction bottle, heat to 60°C to initiate polymerization, and then drop the remaining prepolymer solution into the reaction bottle, controlling the dropping time to 2.5 h; after the dropwise addition is completed, keep warm for 1 h, then add 12 g of triethylamine to neutralize; finally, add 365 g of deionized water into the reactor for dispersion to obtain a reverse thermosensitive copolymer.

[0053] Detection:

[0054] 1. The basic properties of the reverse thermosensitive copolymers prepared in the above Examples 1-6 were tested, and the results are shown in the following table:

[0055] Basic properties of reverse thermosensitive reversible aqueous dispersions

[0056]

[0057] 2. The viscosity changes of the reverse thermosensitive copolymers prepared in the above Examples 1-6 under different temperatures were detected. Figure 1 ;

[0058] Depend on Figure 1It can be seen that the thermosensitive copolymers of Examples 1-6 all have reverse temperature-sensitive changes, and the reverse thermosensitive polymer prepared in Example 1 has the highest viscosity at about 30°C; the reverse thermosensitive polymer prepared in Example 2 has the highest viscosity at about 15°C; the reverse thermosensitive polymer prepared in Example 3 has the highest viscosity at about 45°C; the reverse thermosensitive polymer prepared in Example 4 has the highest viscosity at about 25°C; the reverse thermosensitive polymer prepared in Example 5 has the highest viscosity at about 35°C; the reverse thermosensitive polymer prepared in Example 6 has the highest viscosity at about 40°C, that is, in actual use, high-viscosity reverse thermosensitive polymer materials at the required temperature can be obtained by adjusting different solid contents and combinations of raw materials, thereby expanding the application range of the material;

[0059] 3. The viscosity change of the reverse thermosensitive copolymer prepared in Example 3 under different pH conditions was tested. Figure 2 ;

[0060] Depend on Figure 2 It can be seen that the reverse thermosensitive copolymer prepared in Example 3 also has the effect of viscosity change when the pH changes, which further improves its application in actual production, overcomes the limitations of existing applications, and expands the scope of application.

[0061] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the sentence "comprise a ..." do not exclude the existence of other identical elements in the process, method, article or device including the elements.

[0062] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A reverse temperature-sensitive copolymer, characterized in that: The reverse thermosensitive copolymer is an aqueous dispersion prepared by mixing effective solid matter with deionized water, and the effective solid matter content of the aqueous dispersion is 5-37%; The effective solid material is made of the following raw materials in parts by mass: 3.8-13.9 parts of hydrophilic monomers containing double bonds, 5.2-20 parts of hydrophobic monomers containing double bonds, 0.01-1 parts of cross-linking agents, 2.8-6.5 parts of cosolvents, 0.06-1.1 parts of initiators, 2.3-6.8 parts of neutralizers, and 0-0.5 parts of emulsifiers; The hydrophilic monomer containing a double bond and the hydrophobic monomer containing a double bond are selected from any one of the following: S1. When the hydrophilic monomer containing a double bond is selected to be a compound of methacrylic acid, acrylic acid and hydroxyethyl acrylate, the hydrophobic monomer containing a double bond is selected to be a compound of methyl methacrylate, styrene, butyl methacrylate and octadecyl methacrylate; S2, when the hydrophilic monomer containing a double bond is selected to be a compound of methacrylic acid, acrylic acid and itaconic acid, the hydrophobic monomer containing a double bond is selected to be a compound of butyl acrylate, styrene, acrylonitrile and 2-ethylhexyl acrylate; S3, when the hydrophilic monomer containing a double bond is selected to be a compound of methacrylic acid and hydroxypropyl acrylate, the hydrophobic monomer containing a double bond is selected to be a compound of methyl acrylate, ethyl acrylate, octadecyl acrylate, vinyl acetate and n-butyl acrylate; S4, when the hydrophilic monomer containing a double bond is selected to be a compound of methacrylic acid, hydroxyethyl methacrylate and acrylic acid, the hydrophobic monomer containing a double bond is a compound of methyl acrylate, hexadecyl acrylate and n-butyl acrylate; S5. When the hydrophilic monomer containing a double bond is selected to be a compound of methacrylic acid, acrylic acid, hydroxyethyl methacrylate and hydroxypropyl acrylate, the hydrophobic monomer containing a double bond is selected to be a compound of methyl acrylate, butyl acrylate and eicosyl acrylate; S6. When the hydrophilic monomer containing a double bond is selected to be a compound of methacrylic acid, acrylic acid and hydroxypropyl methacrylate, the hydrophobic monomer containing a double bond is selected to be a compound of ethyl acrylate, butyl acrylate, isooctyl acrylate, octadecyl methacrylate, methyl methacrylate and acrylonitrile; The preparation method of the reverse temperature-sensitive copolymer comprises the following steps: (1) fully mixing a hydrophilic monomer containing a double bond, a hydrophobic monomer containing a double bond, an initiator, and a cosolvent to obtain a prepolymer solution for use; (2) taking a portion of the above prepolymer solution and heating it to initiate polymerization, then dropping the remaining prepolymer solution to carry out polymerization reaction, and keeping the temperature for 0.5-2h after the dropwise addition is completed to obtain a polymer solution; (3) adding a neutralizing agent to the polymer solution in step (2) to carry out a neutralization reaction, and obtaining a neutralized solution for use; (4) adding an emulsifier and deionized water to the neutralized solution in the above step (3) to disperse the solution, thereby obtaining a water dispersion which is a reverse temperature-sensitive copolymer.

2. A reverse thermosensitive copolymer according to claim 1, characterized in that: The initiator is at least one of azobisisobutyronitrile, azobisisovaleronitrile, azobisisoheptanenitrile, benzoyl peroxide, and dodecanoyl peroxide.

3. A reverse thermosensitive copolymer according to claim 1, characterized in that: The crosslinking agent is at least one of divinylbenzene, ethylene glycol diacrylate, triethylene glycol diacrylate, polyethylene glycol diacrylate, pentaerythritol triacrylate, and N,N-methylenebisacrylamide.

4. A reverse thermosensitive copolymer according to claim 1, characterized in that: The neutralizing agent is at least one of triethanolamine, diethanolamine, dimethylethanolamine, N-methyldiethanolamine, N-ethyldiethanolamine, N-propyldiethanolamine, N-butyldiethanolamine, triethylamine, 2-amino-2-methylpropanol, aminopropanol, and N-ethylmorpholine.

5. A reverse thermosensitive copolymer according to claim 1, characterized in that: The co-solvent is at least one of ethanol, ethylene glycol, propylene glycol, butanol, ethylene glycol butyl ether, propylene glycol butyl ether, propylene glycol methyl ether acetate, dipropylene glycol methyl ether, and dipropylene glycol dimethyl ether.

6. A reverse thermosensitive copolymer according to claim 1, characterized in that: The portion of the prepolymer liquid that is heated and polymerized in step (2) is 5-25% of the total prepolymer liquid, and the temperature for heating and initiating the polymerization is 60-85°C.

7. An application of the thermosensitive copolymer according to claim 1 in the fields of thermosensitive sensors, pH response sensors, thermosensitive intelligent response medical dressings, and cosmetics.

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