TWI610951B - Organic-inorganic hybrid siloxane hydrogel composition manufacturing method - Google Patents

Abstract

The invention discloses a preparation method of an organic-inorganic mixed oxime hydrogel composition, which uses a terminal hydroxyl group oxime macromolecule and an inorganic decane coupling agent as a raw material to carry out a reaction under heating and an alkaline environment. After forming a clear transparent solution, it is directly mixed with hydrophilic 2-hydroxyethyl methacrylate and methacrylic acid to form a photopolymerizable organic-inorganic mixed oxime hydrogel composition without causing phase In the case of separation, and no need to add diluent or organic solvent treatment in the process, the organic-inorganic hybrid oxime alkane obtained after heating and curing by ultraviolet light has high light transmittance and dimensional stability, and the future can be Widely used in the optical, medical and coating industries.

Description

Method for preparing organic-inorganic mixed oxirane water gel composition

The invention relates to an organic-inorganic hybrid decane hydrogel, in particular to a preparation method of an organic-inorganic hybrid decane hydrogel composition.

The organic-inorganic hybrid oxime hydrogel has become a highly attracting material in recent years due to its high water content and high oxygen permeability. Conventional organic-inorganic hybrid oxime hydrogels are usually prepared by using a macromolecular siloxane having a hydrophilic functional group as a raw material and polymerizing with a hydrophilic monomer. However, due to the hydrophobicity of the macromolecular molecules, there are more restrictions on the ratio of hydrophilic monomers and diluents during the polymerization process, otherwise there will be phase separation, which also limits the content of bismuth in the water gel, which in turn affects Its oxygen permeability. On the other hand, due to the mechanical and physical properties of the macromolecular macromolecule itself, it needs to be treated with a volatile organic solvent in the process to maintain the wettability and dimensional stability of the surface, so that the process is safe and Environmental considerations also increase the cost of the manufacturing process.

Many experts are working on this aspect. As disclosed in U.S. Patent No. 2009200692, a hydrophilic material is applied to the surface of the hydrophobic gel to form a sandwich structure to enhance its hydrophilicity. World Patent WO 2008116132 A2, which discloses a decane prepolymer containing a hydrophilic polymer chain, which is then made into a hydrophobic gel contact lens. U.S. Patent No. 8,158,695, the addition of a diluent to the process to form a compatible mixture of the oxime and the hydrophilic polymer. In addition, such as U.S. Patent No. 2010,296,049, which discloses a polyoxyalkylene crosslinkable prepolymer having an ethylenically unsaturated group at its end, which can undergo reversible addition fragmentation chain transfer (RAFT) The radical polymerization method is polymerized with a hydrophilic monomer. U.S. Patent No. 2008,132,666 discloses a fumaric acid derivative which contains a hydrophilic group and a hydrazine-containing alkyl group and has good oxygen permeability. In addition, there is also literature discussing the use of a mercapto group on a siloxane monomer to polymerize with a hydrophilic monomer to impart high oxygen permeability, hydrophilicity, and good biocompatibility to the hydrophobic gel. Alternatively, ultraviolet (UV) photopolymerization of decane, 2-hydroxyethyl methacrylate (HEMA) and nitrogen-vinyl-nitrogen ketone (NVP) to form a high water content, high oxygen permeability and mechanical strength Water gel.

However, in the related literatures of existing literatures or patents, there are still limitations on the use of materials, complicated processes, and problems in product characteristics and biocompatibility. Therefore, technical breakthroughs are still needed at this stage. In view of this, the present invention proposes a novel organic-inorganic hybrid oxime hydrogel composition preparation method, which is not only different from the materials and processes used in the prior art, but also can effectively overcome various defects thereof.

The main object of the present invention is to provide a method for preparing an organic-inorganic mixed decane hydrogel composition, which can improve the traditional hydrophobic rubber material and the process, and can uniformly disperse the hydrophobic siloxane precursor in the hydrophilic single. In the body, there is no phase separation, and the ratio of the hydrophobicity of the macromolecular molecules in the polymerization process is reduced.

Another object of the present invention is to provide a method for preparing an organic-inorganic mixed decane hydrogel composition, which is simple in process, does not require the addition of a diluent, and does not require an organic solvent treatment, and the organic formed by the composition - The inorganic mixed decane hydrogel has good dimensional stability, high hydrophilicity, high visible light transmittance and good biocompatibility, and can be widely used in the medical materials, optical and coating industries in the future.

In order to achieve the above object, the present invention provides an organic-inorganic mixed oxirane water a gum composition formed from a hydrolytic condensation polymerization product of the first mixture, the first mixture comprising a second mixture and a 2-hydroxyethyl methacrylate (HEMA) monomer, methacrylic acid (MAA), and a second mixture Is a clear transparent solution formed by covalent bonding of a terminal hydroxyl group of a decane macromolecule and an inorganic decane coupling agent, and the second mixture is added with a 2-hydroxyethyl methacrylate (HEMA) monomer and a The base acrylic acid (MAA) is mixed to form a first mixture, and after the first mixture is reacted, a clear and transparent organic-inorganic mixed decane hydrogel composition is formed. The organic-inorganic mixed oxime hydrogel composition can be added with a photoinitiator to form a highly transparent organic-inorganic hybrid decane hydrogel by heat curing by ultraviolet light.

Furthermore, the present invention also provides a transparent film having a drug-transporting function, which comprises the organic-inorganic mixed oxime hydrogel composition as described above.

In addition, the present invention also provides a method for preparing an organic-inorganic mixed decane hydrogel, which comprises mixing a terminal hydroxyl group of a decane macromolecule with an inorganic decane coupling agent, and performing the heating and alkaline environment. The reaction, after clarifying the transparent solution, is directly mixed with 2-hydroxyethyl methacrylate (HEMA) monomer and methacrylic acid (MAA) to form a clear and transparent organic-inorganic mixed oxirane water. The gum composition is produced without phase separation. Thereafter, a photoinitiator can be further added for ultraviolet light polymerization to form a highly transparent organic-inorganic hybrid hydroxane hydrogel.

The purpose, technical content, features and effects achieved by the present invention will be more readily understood by the detailed description of the embodiments.

Fig. 1 is a flow chart showing the preparation method of the organic-inorganic mixed oxime hydrogel composition provided by the present invention.

2 is a view showing the preparation process of an organic-inorganic hybrid decane hydrogel according to an embodiment of the present invention Schematic.

Fig. 3 is a 29Si NMR spectrum of an organic-inorganic hybrid decane hydrogel according to an embodiment of the present invention.

Fig. 4 is a transmission electron microscope microstructure of an organic-inorganic hybrid decane hydrogel according to an embodiment of the present invention.

Fig. 5 is an X-ray diffraction pattern of an organic-inorganic hybrid decane hydrogel according to an embodiment of the present invention.

Figure 6 is a graph showing the cytotoxicity test of an organic-inorganic hybrid decane hydrogel having different PDMS contents according to an embodiment of the present invention; wherein HAS 7.7%, HAS 14.2%, and HAS 20% represent 7.7%, respectively. 14.2%, 20% PDMS content.

Referring to Fig. 1, a flow chart of a method for preparing an organic-inorganic hybrid decane hydrogel composition of the present invention will be described. The steps are as follows: First, as in step S10, a macromolecular and inorganic group using a terminal hydroxyl group. The decane coupling agent is used as a raw material, and is uniformly mixed in a warm and alkaline environment, so that the inorganic decane coupling agent itself hydrolyzes to produce a silanol group, and the terminal hydroxyl group of the macromolecular siloxane molecule After condensation, a covalent bond is formed to form a clear transparent solution without phase separation.

In the present invention, the oxoxane macromolecule may be polydimethylsiloxane (PDMS) in an amount of about 0.1 to 50% by weight. The inorganic decane coupling agent may be selected from the group consisting of 3-aminopropyltriethoxysilane (APTES), 3-aminopropyltrimethoxysilane (APTMS), and trimethylol. Trimethyl siloxysilane (TRIS), tris-(trimethylsiloxysilyl)propyl vinyl carbamate (TPVC), tetraethyl orthosilicate , TEOS) and ethylene triethyl decane (Vinyl triethoxy silane), the content of which is about 10 to 50% by weight. Further, the oxoxane macromolecule and the inorganic decane coupling agent can be reacted at a temperature of 30 to 100 ° C and an aqueous sodium hydroxide solution.

Then, as in step S20, 2-hydroxyethyl methacrylate (HEMA) monomer and methacrylic acid (MAA) are added to the aforementioned clear transparent solution, and the content of 2-hydroxyethyl methacrylate (HEMA) may be about 30. - 80% by weight. The methacrylic acid (MAA) content can be from about 0.1% to about 10% by weight. The clarified transparent solution can be uniformly mixed with a 2-hydroxyethyl methacrylate (HEMA) monomer and methacrylic acid (MAA), and the sterol group and a part of the 2-hydroxy group produced by the hydrolysis of the inorganic decane coupling agent. The hydroxyl group of the ethyl methacrylate (HEMA) monomer is also covalently bonded after dehydration to form a photopolymerizable organic-inorganic hybrid oxime hydrogel composition.

The organic-inorganic mixed hydroxane hydrogel composition has a different structure of a oxoxane structure such as T ⁰ _R , T ₁ , T ₂ or T ₃ , and the chemical formula thereof is Si(CH ₂ ) ₃ (OH) _{3 , respectively.} (SiO)Si(CH ₂ ) ₃ (OH) ₂ , (SiO) ₂ Si(CH ₂ ) ₃ OH and (SiO) ₃ Si(CH ₂ ) ₃ , wherein T ⁰ _R : 矽 atom is not with another Silane molecules bond, T _1: silicon atoms by Si siloxane bond with a silane-molecules bond, T _2: silicon atoms by Si siloxane bonds and two Silane molecules bonded to T _3: silicon atoms by The bond is formed by a decane bond with three decane molecules. And the T ₃ form of the decane structure may comprise a plurality of cerium oxide nanoparticles having a size of about 5 to 100 nanometers (nm).

Moreover, the organic-inorganic mixed oxime hydrogel composition can be added with a photoinitiator, and the oxirane can be uniformly dispersed in polymorphic form of poly(2-hydroxyethyl methacrylate) in different forms by ultraviolet crosslinking. (HEMA) organic-inorganic hybrid oxime hydrogel, and the formed organic-inorganic hybrid decane hydrogel has high light transmittance. Furthermore, the organic-inorganic hybrid decane hydrogel composition can be further used to produce a transparent film having a drug transport function.

Next, the present invention discloses an embodiment of an organic-inorganic mixed decane hydrogel composition, the composition of which specifically comprises a poly(dimethylsiloxane), bis(hydroxyalkyl)terminated, Referred to as PDMS) A clear transparent solution formed by 3-aminopropyltriethoxysilane (hereinafter referred to as APTES), followed by 2-hydroxymethyl acrylate (HEMA) and A After methacrylic acid (hereinafter referred to as MAA), the product of the hydrolysis condensation polymerization is carried out, that is, the organic-inorganic mixed hydroxane hydrogel composition, and further, an organic-inorganic mixed hydroxane hydrogel is prepared. The detailed preparation steps include:

(1) Preheat the PDMS to above 50 °C.

(2) Add APTES and mix evenly.

(3) The reaction was stirred at 50 ° C or more for 6 hours or more, and HEMA was added thereto, followed by uniform mixing.

(4) Add MAA to make it evenly mixed.

(5) After the reaction for 6 hours or more, the organic-inorganic mixed hydroxane hydrogel composition of the present invention can be obtained.

(6) To this composition, Darocur 1173, which is a photoinitiator, was uniformly mixed and irradiated with ultraviolet light having a wavelength of 365 nm (nm) for 30 minutes to carry out polymerization.

(7) After immersing in 95% alcohol for 5 hours to remove unreacted monomers, soaking them with 50% alcohol for 5 hours, finally soaking in deionized water for 5 hours, drying in an oven to obtain organic-inorganic mixed oxygen Dry water of alkane glue.

In this embodiment, the hydrophobic material PDMS and the hydrophilic monomer HEMA can be sufficiently mixed without causing phase separation; in the heating and alkaline environment, the APTES hydrolysis and further condensation reaction are catalyzed to form various kinds of helium oxygen. The inorganic phase of the alkane forms a covalent bond with the terminal hydroxyl group of the PDMS and forms another covalent bond with the hydroxyl group of the part of the HEMA monomer to form a photopolymerizable organic-inorganic hybrid hydroxane hydrogel composition. After the cross-linking by ultraviolet light, the obtained organic-inorganic mixed decane hydrogel can uniformly disperse different forms of oxane in poly(2-hydroxyethyl methacrylate) (poly HEMA). Please refer to FIG. 2 , which is a structural diagram of the preparation process of the organic-inorganic mixed oxime hydrogel composition and the polymerization process of the organic-inorganic hybrid oxime hydrogel. intention.

In this example, by hydrogen 1 nuclear magnetic resonance ( ¹ H NMR) analysis, it can be found that the peak of the -OH functional group originally representing PDMS in the ¹ H NMR spectrum of PDMS, after the PDMS and APTES reaction, the peak Not presented, it can be proved that APTES and PDMS are successfully covalently bonded. Moreover, by 矽29 nuclear magnetic resonance ( ²⁹ Si NMR) analysis, it was observed that APTES formed a variety of different forms of oxane under the catalysis of alkaline environment. As shown in the ^29th NMR spectrum of Fig. 3, peaks of T ₁ (-53 to -54 ppm), T ₂ (-59 to -61 ppm), and T ₃ (-66 to -69 ppm) can be found, which respectively represent (SiO )Si(CH ₂ ) ₃ (OH) ₂ , (SiO) ₂ Si(CH ₂ ) ₃ OH and (SiO) ₃ Si(CH ₂ ) ₃ structure, as can be seen from the spectrum, the structure of the oxoxane is mainly T ₂ and T ₃ , and T ₃ represents the final structure of the complete reaction of the decyl group, showing that most of the fluorenyl groups attached are hydrolyzed to the Si-O-Si structure.

Furthermore, please refer to Fig. 4, observe the microstructure of the organic-inorganic mixed oxime hydrogel by a transmission electron microscope, and find that the APTES dehydrates to form the final structure of the T3 phase, and aggregates to form a nanoscale. Small particles. This structure corresponds to the formation of the cerium oxide structure in the T3 phase, which is about 20-30 nm. This cerium oxide structure region can be proved by an X-ray diffraction spectrum. Referring to Fig. 5, characteristic peaks generated by X-ray diffraction can be observed, and the characteristic peak exhibited at 2θ of about 13 degrees and about 30 degrees is a cerium oxide crystal phase.

Then, the organic-inorganic mixed decane hydrogel of different PDMS content was immersed in a deionized aqueous solution to fully swell, and then subjected to ultraviolet-visible light transmittance experiments, and it was found that in the visible wavelength range (400- Within 800 nm), the organic-inorganic hybrid decane hydrogel with different PDMS content (7.7%, 14.2%, 20% PDMS content) can maintain a penetration of more than 90%, showing organic content with different PDMS content - Inorganic blended aerobicane water gels have very high transparency.

In addition, in order to understand the biocompatibility of this organic-inorganic hybrid decane hydrogel The effect of different PDMS content of organic-inorganic mixed decane hydrogel, 24-hour cytotoxicity test on bovine corneal endothelial cells, the results are shown in Figure 6, organic-inorganic mixed oxirane water with different PDMS content All of the gels have a cell viability of over 85%, indicating good cell compatibility.

In summary, the organic-inorganic hybrid oxime hydrogel composition provided by the present invention, a preparation method and application thereof, and a hydroxyalkylene macromolecule and an inorganic decane coupling agent using a terminal hydroxyl group of a highly permeable material In the heating and alkaline environment, catalyzing the hydrolysis of the inorganic decane coupling agent and further condensation reaction to form a plurality of inorganic phases of the oxane and covalently bonding with the macromolecular bond of the terminal hydroxyl group Forming a clear transparent solution, this solution can be mixed in any proportion to the traditional hydrocolloid material 2-hydroxyethyl methacrylate (HEMA) monomer and methacrylic acid (MAA), and with a part of 2-hydroxyethyl methacrylate monomer Forming a bond to form a photopolymerizable organic-inorganic mixed oxime hydrogel composition, and after adding a photoinitiator, the oxirane can be uniformly dispersed in the polymorphous form in different forms by ultraviolet light interlinking. - Hydroxyethyl methacrylate in polyoxyl (poly HEMA) water gel, while avoiding the case where the conventional direct mixing hydrophobic oxane macromolecule is easily phase-separated from the hydrophilic group.

The organic-inorganic mixed oxime hydrogel composition provided by the invention, the preparation method and the application thereof have the advantages of simple process, no need to add diluent in the process, and no organic solvent treatment, thereby reducing the stress coefficient caused by the oxime The organic-inorganic hybrid oxime hydrogel, which is added by ultraviolet light polymerization, has high transparency, good dimensional stability, and good biocompatibility, and can be widely used in the optical, medical materials and coating industries in the future. field.

The above is only the preferred embodiment of the present invention and is not intended to limit the scope of the present invention. Therefore, any changes or modifications of the features and spirits of the present invention should be included in the scope of the present invention.

Claims (7)

The invention relates to a method for preparing an organic-inorganic mixed oxime hydrogel composition, which comprises the steps of: coupling a terminal hydroxyl group oxirane macromolecule with an inorganic decane coupling agent at a temperature of 30-100 ° C in an alkaline environment. , to make it evenly mixed, to form a clear transparent solution after the reaction; and to add a 2-hydroxyethyl methacrylate (HEMA) monomer and monomethacrylic acid (MAA) in the clear transparent solution, to make it evenly mixed, the reaction The organic-inorganic hybrid decane hydrogel composition is then formed. The method for producing an organic-inorganic mixed oxime hydrogel composition according to claim 1, wherein the oxime macromolecule is reacted with the inorganic decane coupling agent in an aqueous solution of sodium hydroxide. The method for preparing an organic-inorganic mixed oxime hydrogel composition according to claim 1, further comprising the step of adding a photoinitiator for ultraviolet light irradiation to carry out polymerization. The method for producing an organic-inorganic hybrid oxime hydrogel composition according to claim 3, wherein the photoinitiator is Darocur 1173. The method for preparing an organic-inorganic mixed oxime hydrogel composition according to claim 1, wherein the inorganic decane coupling agent is selected from the group consisting of 3-aminopropyl triethoxysilane (APTES). , 3-aminopropyltrimethoxysilane (APTMS), trimethyl siloxysilane (TRIS), tris-(trimethyldecyloxydecane) propylvinyl Tris-(trimethyl siloxysilyl) propyl vinyl carbamate (TPVC), Tetraethyl orthosilicate (TEOS) and Vinyl triethoxy silane. The method for preparing an organic-inorganic hybrid oxime hydrogel composition according to claim 1, wherein the oxyalkylene macromolecule is polydimethyl siloxane (PDMS). The method for preparing an organic-inorganic mixed oxime hydrogel composition according to claim 1, wherein the siloxane has a macromolecular content of 0.1-50% by weight, and the inorganic decane coupling agent content is 10-50. The weight %, the 2-hydroxyethyl methacrylate (HEMA) content is from 30 to 80% by weight, and the methacrylic acid (MAA) content is from 0.1 to 10% by weight.