TW201819477A - Hydrophilic silicon-containing pre-polymer and preparation method and applications thereof through a condensation polymerization reaction of hydroxyl end-blocked polydimethylsiloxane and polyethylene glycol serving as raw materials - Google Patents

Abstract

This invention provides a hydrophilic silicon-containing pre-polymer and a preparation method and applications thereof, wherein a hydrophilic silicon-containing pre-polymer containing polyethylene glycol-polydimethylsiloxane is prepared by carrying out a condensation polymerization reaction using hydroxyl end-blocked polydimethylsiloxane and polyethylene glycol as raw materials. By using the hydrophilic silicon-containing pre-polymer, the high hydrophobicity of traditional polydimethylsiloxane can be improved, the compatibility among hydrophilic hydrophilic monomers can be improved, the limit in addition proportion of the polydimethylsiloxane in a polymerization process due to the hydrophobicity of polydimethylsiloxane can be significantly reduced, and a chemical solvent is not required to be added, thereby greatly expanding the application range of a silicon hydrogel material.

Description

Hydrophilic silicon-containing prepolymer, preparation method and application thereof

The invention relates to a hydrophilic silicon-containing prepolymer, in particular a hydrophilic silicon-containing prepolymer prepared by a condensation polymerization reaction and a preparation method thereof, and the hydrophilic silicon-containing prepolymer is further used for preparing the same. Silicone water glue material and contact lens applications.

Silicone water glue is an organic polymer material. In the application of contact lenses, the main problem is to provide contact lens oxygen transmission without relying on water molecules. However, silicon molecules have extremely high hydrophobic properties. In addition to phase separation with hydrophilic monomers, they also cause the surface of silicone hydrogel lenses to exhibit hydrophobic properties, which can easily deposit deposits and cause eye discomfort. Therefore, in order to synthesize hydrophilic silicon molecules suitable for silicone hydrogel contact lenses, and in order to provide a lens with high oxygen permeability and improve compatibility with hydrophilic monomers, many studies have continuously proposed its improvement.

Among them, taking the US patent case US 20140362339 as an example, it discloses a "silicone hydrogel soft contact lens having wettable surface" having a wettable surface. This patented technology is chemically bonded Modification of the polyethylene glycol group in the silicon molecular structure can solve the problem of hydrophobicity of the lens surface caused by polypropylene molds. On the other hand, during the lens forming process, there is no need to undergo surface treatment or add high hydrophilicity. Polymer, and the lens still has a highly wettable surface.

In addition, please refer to the journal Colloids and Surfaces B: Biointerfaces, Volume 71, 2009, pp. 36-44, published in the article "Poly (dimethylsiloxane-carbamic acid) Fabrication and characterization of ophthalmically compatible hydrogels composed of poly (dimethylsiloxane-urethane) / Pluronic F127) ", this journal article is based on Polydimethylsiloxane is the main structure, and the terminal functional group (-OH) is used to chemically bond with poly (ethylene glycol) methacrylate (PEGMA) to make the polydimethylsiloxane. Siloxane has reactive functional groups and is suitable for free radical polymerization.

Another US patent case, US 20140362339, discloses a "hydrophilic polysiloxane macromonomer, and production and use of the same". This patented technology is also chemically bonded. Way, the polyethylene glycol group is modified at the end and the side of the silicon molecular structure, and the polyethylene glycol molecules at the side can increase the degree of grafting with the increase of the repeating units of the silicon molecule, so that the silicon water When the glue has high oxygen permeability, it can retain a certain degree of hydrophilic properties.

In the above-mentioned related literatures, polyethylene glycol is used to modify the siloxane structure to solve the problem of the hydrophobicity of the siloxane structure. However, because they are all chemical grafting (Graft) technology, the reaction steps are more complicated. The oxygen capacity depends on the structure of the siloxane. When the repeating unit of the siloxane is higher, the hydrophobic property is relatively significant, which is likely to cause the limitation of the synthetic material and cause the grafting effect to be inconspicuous.

The reason is that the inventors have considered this, and conceived a hydrophilic silicon-containing prepolymer, and a preparation method and application thereof. In addition to a simple preparation method, the siloxane repeating unit can be controlled, and polyethylene glycol can also be controlled. The composition of the alcohol and the siloxane structure is not only different from the synthetic method of the prior art, but also can effectively overcome its various shortcomings; its specific architecture and implementation will be described in detail below.

The main object of the present invention is to provide a hydrophilic silicon-containing prepolymer, and a preparation method and application thereof, which are capable of preparing a polyethylene glycol-polydimethylsiloxane-containing hydrophilic polymer by using a condensation polymerization reaction. Silicon prepolymer. This hydrophilic silicon-containing prepolymer can improve the high hydrophobicity of traditional polydimethylsiloxane, and provide compatibility with hydrophilic monomers, which can further free radical chains through hydrophilic monomers. Co-polymerization reaction to form a silicone gel with good hydrophilicity and oxygen permeability, without the need to add a chemical solvent, and greatly reduce the limitation of the proportion of polydimethylsiloxane in the polymerization process due to its hydrophobicity, and further Improve the application range of silicone hydrogel materials.

Another object of the present invention is to provide a hydrophilic silicon-containing prepolymer, and a preparation method and application thereof. The preparation method is simple, and the prepolymer length or the hydrophilic-hydrophobic interval can be adjusted by changing simple parameters during the polymerization process. Proportion, with better material design flexibility.

Another object of the present invention is to provide a hydrophilic silicon-containing prepolymer, and a preparation method and application thereof. The prepolymer has a reactive functional group at the end of the hydroxyl group (-OH), and can use chemical bonding to graft functional molecules. In the future, it can be widely used in medical materials, optics and other technical fields.

To achieve the above object, the present invention discloses a hydrophilic silicon-containing prepolymer having the following structural formula (I): (I) wherein n is an integer from 8 to 220; m is 25; R is an alkyl group from C1 to C4; and p is an integer from 1 to 3.

On the other hand, the present invention also discloses a method for preparing a hydrophilic silicon-containing prepolymer. The steps include the following steps: firstly, polydimethylsiloxane having a terminal hydroxyl group and polyethylene glycol are mixed as a raw material in a diluent; To form a reaction mixture, and then add an isocyanate compound and a catalyst to the reaction mixture, and perform a condensation polymerization reaction at a temperature of room temperature to 40 ° C to form a hydrophilic silicon-containing prepolymer having the structural formula (I) As shown above.

Further, the present invention also discloses a silicone hydrogel composition. The hydrophilic silicon-containing prepolymer is modified with a terminal functional group to form a siloxane macromonomer. Then, a 10-50 weight percent can be obtained. Mixed with 30-70 weight percent of the hydrophilic monomer, and then add an effective amount of a photoinitiator and a cross-linking agent, such as 0.5-2 weight percent of the light initiator and 0.5-1 weight Percentage of cross-linking agent to form a silicone hydrogel mixture to help the synthesis of silicone hydrogel lenses.

Still further, the present invention further discloses a silicone hydrogel lens, which is one of the silicone hydrogel lenses prepared with the above-mentioned silicone hydrogel composition and having good oxygen permeability and wearing comfort.

In the following, detailed descriptions will be made through specific embodiments in conjunction with the accompanying drawings to make it easier to understand the purpose, technical content, features and effects of the present invention.

Please refer to FIG. 1. The manufacturing process of the preparation method of the hydrophilic silicon-containing prepolymer provided by the present invention includes detailed steps including:

First, as in step S120, a polydimethylsiloxane with a hydroxyl end as a main structure and polyethylene glycol as a chain extender is used. The two and the diluent are placed in a separate four-neck reaction flask under nitrogen. After being homogenized with mechanical stirring under conditions, a reaction mixture was formed.

In the present invention, the polydimethylsiloxane having a terminal hydroxyl group may be a poly (dimethylsiloxane) dialkanol (PDMS-diol), which has the following structural formula (II): (II) where m is 25.

Poly (ethylene glycol) (PEG) has a molecular weight between 400 and 10,000, and has the following structural formula (III): (III) where n is an integer between 8 and 220.

The diluent may be Tetrahydrofuran (THF).

Then, in step S140, the isocyanate compound and a small amount of catalyst are added to the reaction mixture, and the condensation polymerization reaction is performed at a temperature of room temperature to 40 ° C. The reaction time is at least 24 hours to form a hydrophilic silicon-containing prepolymer. Thing.

In this step, the isocyanate compound may be isophorone diisocyanate (IPDI); and the catalyst may be dibutyltin dilaurate (DBTDL).

According to the present invention, in terms of moles, the content ratio of polydimethylsiloxane, polyethylene glycol and isocyanate in the reaction mixture at the end of the hydroxyl group is preferably 1: 1: 0.5 to 2 to form the hydrophilic silicon-containing prepolymer of the present invention. The reaction formula (a) is as follows: (A) wherein n is an integer from 8 to 220; m is 25; R is an alkyl group from C1 to C4; and p is an integer from 1 to 3.

Therefore, the present invention is to prepare the hydrophilicity of the above reaction formula (a) by mixing the above two kinds of reactants (polydimethylsiloxane with a hydroxyl group at the end and polyethylene glycol) through a condensation polymerization reaction. The silicon-containing prepolymer has the structural formula (I): (I) wherein n is an integer from 8 to 220; m is 25; R is an alkyl group from C1 to C4; and p is an integer from 1 to 3.

In the following, a plurality of specific embodiments of the present invention will be described in detail. Polyethylene glycol (PEG) and dihydroxy polydimethylsiloxane (PDMS-diol) with different molecular weights are used as raw materials, and tetrahydrofuran (THF) is used as a raw material. Diluent, and add isoflurone diisocyanate (IPDI) and dibutyltin dilaurate (DBTDL) as catalysts to prepare a hydrophilic silicon-containing prepolymer. Continuing, and conducting molecular weight detection by gel permeation chromatography (GPC), and observing the change in the measured molecular weight, to prove the feasibility of the technology of the invention; more monomer compatibility test to prove the invention The hydrophilic silicon-containing prepolymer has good compatibility with hydrophilic monomers.

Example 1: 23.3 g (12.5 mmol) of bishydroxypolydimethylsiloxane (PDMS-diol) with an average molecular weight Mw = 1860, 5 g (12.5 mmol) of polyethylene glycol with an average molecular weight of Mw = 400 ( PEG) and 40 g of tetrahydrofuran (THF) were placed in a separate four-necked reaction flask, and mechanically stirred under nitrogen to make it homogeneous. Then, 1.4 g (6.25 mmol) of isoflurone diisocyanate (IPDI) and about 0.1 were added. g of dibutyltin dilaurate (DBTDL) was reacted at room temperature for 24 hours. After the reaction was completed, the molecular weight was measured by a gel permeation chromatography (GPC).

Example 2: 4.7 g (2.5 mmol) of bishydroxypolydimethylsiloxane (PDMS-diol) with an average molecular weight Mw = 1860, 10 g (2.5 mmol) of polyethylene glycol with an average molecular weight Mw = 10000 ( PEG) and 200 g of tetrahydrofuran (THF) were placed in a separate four-necked reaction flask, and mechanically stirred under nitrogen to make it homogeneous. Then, 0.44 g (2 mmol) of isoflurone diisocyanate (IPDI) and about 0.1 were added. g of dibutyltin dilaurate (DBTDL) was reacted at 40 ° C for 24 hours. After the reaction was completed, the molecular weight was measured by a gel permeation chromatography (GPC).

Example three: 1.88 g (1 mmol) of bishydroxypolydimethylsiloxane (PDMS-diol) with an average molecular weight Mw = 1860, 10 g (1 mmol) of polyethylene glycol with an average molecular weight Mw = 4000 ( PEG) and 200 g of tetrahydrofuran (THF) were placed in a separate four-necked reaction flask, and mechanically stirred under nitrogen to make it homogeneous. Then, 1.1 g (5 mmol) of isoflurone diisocyanate (IPDI) and about 0.1 were added. g of dibutyltin dilaurate (DBTDL) was reacted at 40 ° C for 24 hours. After the reaction was completed, the molecular weight was measured by a gel permeation chromatography (GPC).

GPC detection: Dissolve the samples obtained in each example in tetrahydrofuran (THF) and configure a concentration of 5mg / mL. At a flow rate of 1mL / min, use tetrahydrofuran (THF) as the mobile phase, and the detection method is refractive index detection. (Refractive Index Detector), and calculate the molecular weight using Polystyrene as a standard. According to the experimental results of GPC analysis, please refer to Table 1. Using unmodified polydimethylsiloxane (PDMS) as a control group, it can be known that the original molecular weight of PDMS is Mn = 2027 and Mw = 3637. The present invention will Dihydroxy polydimethylsiloxane (PDMS-diol) was combined with various PEGs with different molecular weights (400 to 10,000) through condensation polymerization to prepare polyethylene glycol-polydimethyl methoxides in Examples 1 to 3. Based on the hydrophilic silicon-containing prepolymer of PEG-PDMS, its molecular weight has been significantly improved. On the other hand, the molecular weight distribution measured in the experiment can be controlled between about 1.5 and 2.0, showing that the hydrophilic silicon-containing prepolymer can effectively control the molecular weight dispersibility in addition to the increase in molecular weight.

Table I Among them, Mn (Number-average Molecular Weight): number average molecular weight; Mw (Weight-average Molecular Weight): weight average molecular weight; and PDI (Polydispersity Index): molecular weight distribution index.

Compatibility test: PDMS and PEG-PDMS of the present invention are separately added to 2-hydroxyethyl methacrylate (HEMA) and mixed uniformly, and compatibility is compared with a hydrophilic monomer (Hydrophilic monomer). The experimental results show that at a fixed ratio (80wt% HEMA and 20wt% PDMS or PEG-PDMS), the PDMS-containing monomer solution appears cloudy, while the PEG-PDMS monomer solution appears transparent and clear, showing that the PEG-PDMS and the The hydrophilic monomers have good compatibility characteristics.

Application of hydrophilic silicon-containing prepolymers: modification of terminal functional groups Take the aforementioned PEG-PDMS with a molecular weight of 400 as an example, take 10 g (3 mmol) of PEG-PDMS and 0.96 g of methacrylic acid-isocyanate ethyl ester (2- Isocyanatoethyl methacrylate (IEM) was placed in a separate four-necked reaction flask, and mechanically stirred under nitrogen to make it homogeneous. Then, using about 0.1 g of dibutyltin dilaurate (DBTDL) as a catalyst, the reaction was performed at room temperature for 24 hours. That is, the modification of the terminal functional group of PEG-PDMS is completed, and it is used as the siloxane macromonomer of the subsequent preparation of the silicone hydrogel composition.

Application of the hydrophilic silicon-containing prepolymer: The preparation of the silicone hydrogel composition is continued. The present invention utilizes the siloxane macromonomer modified by the terminal functional group of the hydrophilic silicon-containing prepolymer disclosed above. Take about 10-50 weight percent, add 30-70 weight percent of the hydrophilic monomer, and an effective amount of the initiator (Initiator), cross-linking agent (Crosslinking agent), such as about 0.5-2 weight percent of the initiator The cross-linking agent is about 0.5-1 weight percent, which is mixed into a silicone hydrogel composition, and the product of the silicone hydrogel composition through a radical chain copolymerization reaction can be prepared into the silicone hydrogel lens of the present invention. . The hydrophilic monomer may be selected from 2-hydroxyethyl methacrylate (HEMA), N-vinylpyrrolidone (NVP) or dimethylaminoethyl methacrylate (N, N -dimethyl acrylamide (DMA); the initiator may be a photoinitiator, and the photoinitiator may be any currently known initiator, for example, Darocur® 1173 (2-hydroxy-2-methyl-1-benzene -1-Acetone, 2-Hydroxy-2-methylpropiophenone (D-1173) or Irgacure® 819 (phenylbis (2,4,6-trimethylbenzoyl) phosphine oxide, phenyl bis (2,4, 6-trimethylbenzoyl) -phosphine oxide (I-819); and the cross-linking agent may be tri (ethylene glycol) dimethacrylate (TEGDMA).

Application of hydrophilic silicon-containing prepolymers: Preparation of silicone hydrogel lenses At the end, about 20 μg of the silicone hydrogel composition is injected into a polypropylene mold, formed by spin molding, and subjected to ultraviolet light (curing strength is about 3) mW / cm ² ) irradiation for 30 minutes to complete the preparation of its silicone hydrogel lens. The lens composition and physical properties are shown in Table 2. The physical property detection method is described later.

Table II

Silicone hydrogel lens detection: 5 lenses were taken for water content detection , and the moisture was wiped with tissue paper and placed on a glass slide. The average weight was wet. Then the silicone hydrogel lens was dried in an oven for 20 hours. After weighing, the average is the dry weight, and the water content is calculated by the following formula. % Moisture content = [(wet weight-dry weight) / wet weight] * 100

Silicone hydrogel lens inspection: oxygen permeability test

1. Measurement of lens current value The silicon hydrogel lens to be tested is immersed in standard saline before testing, and equilibrated at room temperature (20 ° C ± 2.0 ° C) for at least 24 hours, and then under test conditions (35 ° C ± 0.5) ℃) Equilibrate for at least 2 hours, place the first silicone hydrogel lens on the polarographic electrode, fix the lens with nylon net and moving sleeve, and record after the detection current value is stable. Remove the lens and take out the second silicone hydrogel lens. After stacking the two silicone hydrogel lenses, place them again and fix them on the polarographic electrode to measure the current value, and measure the stack of three and four silicone hydrogels according to the above steps. The current value of the lens. Dk ⁄ t = ((I-Id)) / (PA × A) × 5.804 × 10 ^-2 I: measured current value; Id: dark current; PA: (atmospheric pressure-water vapor pressure) x oxygen in the atmosphere %; And A: cathode area of polarographic electrode (cm ² ).

2. The edge effect correction (Correction for edge effects): (corrected) t / Dk = t / Dk ( uncorrected) × [1 + ((2.35 × t)) / Dcathode] wherein, Dcathode is the cathode of the polarographic electrode diameter.

3. The side effect correction layer (Correction for boundary layer effects): The stack 4 t / Dk values of thickness t was plotted, a straight line can be obtained binary linear equation of FIG, after the slope of this line of 1 / Dk is the correction Dk Countdown. Dk = Barrer Unit: [(cm ² / sec) (ml O ₂ ) / (ml * mmHg) × 10 ^-11 ]

In summary, the present invention uses polydimethylsiloxane as the main structure with a terminal hydroxyl group and polyethylene glycol as a chain extender, and uses condensation polymerization reaction to form polyethylene glycol-polydimethyl silicon. The hydrophilic silicon-containing prepolymer of oxane has the advantages of simple manufacturing process, easy adjustment of the length of the prepolymer, or the ratio of hydrophilic-hydrophobic ratio, and better material design flexibility. Furthermore, this hydrophilic silicon-containing prepolymer can overcome the hydrophobicity problem of the siloxane structure in particular, and can effectively provide compatibility with hydrophilic monomers and help further co-exist with free-radical chain linkages between hydrophilic monomers. During the polymerization reaction, no chemical solvent is required in the process, and the limitation of the addition ratio of the siloxane structure can be reduced. At the same time, since the hydrophilic silicon-containing prepolymer prepared by the present invention has a reactive functional group -hydroxyl (-OH) at the end, it can be used The chemical bonding method and the grafting of functional molecules have a wide range of applications.

The above-mentioned embodiments are only for explaining the technical ideas and characteristics of the present invention. The purpose is to enable those skilled in the art to understand the contents of the present invention and implement them accordingly. When the scope of the patent of the present invention cannot be limited, That is, any equivalent changes or modifications made in accordance with the spirit disclosed in the present invention should still be covered by the patent scope of the present invention.

no

FIG. 1 is a flowchart of a method for preparing a hydrophilic silicon-containing prepolymer according to the present invention.

Claims (16)

A hydrophilic silicon-containing prepolymer having the following structural formula (I): (I) wherein n is an integer from 8 to 220; m is 25; R is an alkyl group from C1 to C4; and p is an integer from 1 to 3. A method for preparing a hydrophilic silicon-containing prepolymer includes the following steps: mixing polydimethylsiloxane with a hydroxyl group at one end and a polyethylene glycol as raw materials in a diluent to form a reaction mixture; And an isocyanate compound and a catalyst are added to the reaction mixture, and a condensation polymerization reaction is performed at a temperature of room temperature to 40 ° C to form the hydrophilic silicon-containing prepolymer, which has the following structural formula (I ): (I) wherein n is an integer from 8 to 220; m is 25; R is an alkyl group from C1 to C4; and p is an integer from 1 to 3. The method for preparing a hydrophilic silicon-containing prepolymer as described in claim 2, wherein the terminal is a polydimethylsiloxane containing a hydroxyl group, the polyethylene glycol and the isocyanate are in the reaction mixture. The molar ratio content ratio is 1: 1: 0.5 ～ 2. The method for preparing a hydrophilic silicon-containing prepolymer according to item 2 of the claim, wherein the polydimethylsiloxane having a hydroxyl group at the end is a dihydroxypolydimethylsiloxane having the structural formula (II) for: (II); and the molecular weight of the polyethylene glycol is between 400 and 10,000, and the structural formula (III) is: (III). The method for preparing a hydrophilic silicon-containing prepolymer according to claim 2, wherein the diluent is tetrahydrofuran. The method for preparing a hydrophilic silicon-containing prepolymer according to item 2 of the claim, wherein the isocyanate is isoflurone diisocyanate. The method for preparing a hydrophilic silicon-containing prepolymer as described in claim 2, wherein the catalyst is dibutyltin dilaurate. The method for preparing a hydrophilic silicon-containing prepolymer according to claim 2, wherein the reaction time of the condensation polymerization reaction is at least 24 hours. A silicone hydrogel composition, comprising: a 10-50 weight percent of a siloxane macromonomer, the siloxane macromolecule single system is prepolymerized with a hydrophilic silicon-containing polymer as described in claim 1 The product is modified by terminal functional groups; a 30-70 weight percent hydrophilic monomer; an effective amount of a photoinitiator; and an effective amount of a crosslinking agent. The silicone hydrogel composition according to claim 9, wherein the hydrophilic silicon-containing prepolymer is modified with a terminal functional group by methacrylic acid-isocyanate ethyl ester. The silicone hydrogel composition according to claim 9, wherein the hydrophilic single system is selected from the group consisting of 2-hydroxyethyl methacrylate (HEMA), N-vinylpyrrolidone, NVP) or N, N-dimethyl acrylamide (DMA). The method for preparing a silicone hydrogel composition according to claim 9, wherein the photoinitiator is 2-hydroxy-2-methyl-1-phenyl-1-acetone or phenylbis (2,4 , 6-trimethylbenzoyl) phosphine oxide. The silicone hydrogel composition according to claim 9, wherein the cross-linking agent is triethylene glycol diacrylate. The silicone hydrogel composition according to item 9 of the claim, wherein the photoinitiator is used in an amount of 0.5-2 weight percent. The silicone hydrogel composition according to item 9 of the claim, wherein the amount of the cross-linking agent used is 0.5-1 weight percent. A silicone hydrogel lens is prepared from the silicone hydrogel composition according to claim 9 of the claim.