Tetrahedral PEG-siloxane hybrid macromonomer and application thereof

Abstract

The invention specifically discloses a tetrahedral PEG-siloxane hybrid macromonomer and application thereof, and relates to the technical field of polymer chemistry. The contact lens prepared from the monomer provided by the invention has the advantages of no micromolecule residue, high wearing comfort, high strength / toughness, high visual clarity, high biological safety, simplified process and the like.

Description

Technical Field

[0001] This invention relates to the field of polymer chemistry, and in particular to a tetrahedral PEG-siloxane hybrid macromonomer and its applications. Background Technology

[0002] Siloxane hydrogel (SiHy) contact lenses, made from hydrated cross-linked polymer materials containing siloxanes and a certain amount of water within a balanced lens polymer matrix, are becoming increasingly popular due to their minimal adverse effects on corneal health caused by their relatively high oxygen permeability. However, the incorporation of siloxanes into contact lens materials can have undesirable effects on the hydrophilicity and wettability of SiHy contact lenses, as silicon is hydrophobic and has a strong tendency to migrate on lens surfaces exposed to air. Contact lens manufacturers have made significant efforts to develop SiHy contact lenses with hydrophilic and wettable surfaces.

[0003] However, existing technologies mostly employ linear macromolecular monomers + crosslinking agents via free radical polymerization, resulting in numerous network defects and difficulty in simultaneously achieving optimal mechanical properties and oxygen permeability / water content. A typical structure is the PEG-PDMS block copolymer described in US11186736B2, but its low mechanical properties are caused by the dispersed functionality of crosslinking points; residual initiators / crosslinking agents lead to poor biocompatibility; and the random distribution of oxygen permeability and water content channels results in high haze. The latest Tetra-PEG uniform network also has defects: the pure hydrogel has an oxygen permeability coefficient <2 barrer, which cannot meet the corneal oxygen demand.

[0004] Therefore, no material has yet achieved a balance in all five aspects: high oxygen permeability, high water content, high modulus, low defects, and room temperature initiator-free curing. Summary of the Invention

[0005] (a) Technical problems to be solved Therefore, one of the main objectives of this invention is to provide a tetrahedral PEG-siloxane hybrid macromonomer and its applications. Contact lenses prepared from the monomer provided by this invention have advantages such as no small molecule residue, high wearing comfort, high strength / toughness, high visual clarity, high biosafety, and simplified manufacturing process.

[0006] (II) Technical Solution To achieve the above objectives, the present invention provides a tetrahedral PEG-siloxane hybrid macromonomer having the structure shown in formula (I); PEGm–X–(Si-arm)n Formula (I), Where X represents a carbamate, amide, or click chemical linker; Si-arm is selected from TRIS, PDMS, or TRIS-b-PDMS; m and n are natural numbers selected from 1 to 99.

[0007] In one embodiment, X is an amide.

[0008] In one embodiment, the Si-arm is a PDMS.

[0009] In one embodiment, m is selected from 4 and / or n is selected from 4.

[0010] In one embodiment, the tetrahedral PEG-siloxane hybrid macromonomer has the structure PEG4-CONH-PDMS4.

[0011] In one embodiment, the molecular weight of the TIS and / or PDMS is 1~10 kDa.

[0012] In one embodiment, the molecular weight of the PEG is 8-12 kDa.

[0013] In another aspect, the present invention provides the application of the aforementioned tetrahedral PEG-siloxane hybrid macromonomer in the preparation of contact lenses.

[0014] In another aspect, the present invention also provides a contact lens containing the aforementioned tetrahedral PEG-siloxane hybrid macromonomer.

[0015] In one embodiment, the contact lens further comprises a second monomer containing clickable functional groups complementary to the tetrahedral PEG-siloxane hybrid macromonomer.

[0016] In one embodiment, the tetrahedral PEG-siloxane hybrid macromonomer and the second monomer are arranged alternately.

[0017] (III) Beneficial Effects This invention provides a tetrahedral PEG-siloxane hybrid macromonomer and its applications. Compared with the prior art, it has the following advantages: 1. The contact lenses prepared from the monomers provided by this invention have advantages such as no small molecule residue, high wearing comfort, high strength / toughness, high visual clarity, high biosafety, and simplified process. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 This is a schematic diagram of the tetrahedral PEG-siloxane hybrid macromolecular monomer structure.

[0020] Figure 2 This is a TEM cross-sectional view of a dual continuous network.

[0021] Figure 3 It is a stress-strain curve.

[0022] Figure 4 It is a three-dimensional performance diagram of oxygen permeability coefficient, water content, and modulus. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0024] Terms and Definitions As used herein, the term "monomer" refers to any molecule capable of reacting with other identical or different molecules to form a polymer or copolymer. Therefore, the term encompasses polymerizable prepolymers and macromonomers, and unless otherwise specified, there is no size limitation on monomers.

[0025] As used herein, the term "siloxane monomer" contains at least one Si-O group and is typically "monofunctional" or "polyfunctional," meaning that it has one polymerizable group or two or more polymerizable groups, respectively. A "non-siloxane monomer" is a monomer that does not contain any Si-O groups.

[0026] As used herein, the term "crosslinker" is any compound with a molecular weight less than about 2,000 and having two or more olefinic unsaturated groups. Therefore, a crosslinker can react with functional groups on two or more polymer chains to bridge one polymer to another. An "acrylate-containing crosslinker" has at least two polymerizable acrylate functional groups and no other types of polymerizable functional groups. A "vinyl-containing crosslinker" has at least two polymerizable vinyl groups (as defined above) and no other types of polymerizable functional groups.

[0027] As used herein, the term "contact lens" refers to a structure that may be placed on or inside the eye of a wearer. Contact lenses can correct, improve, or alter a user's vision, but are not required to do so. Contact lenses can be made of any suitable material known in the art or subsequently developed, and can be soft, rigid, or hybrid lenses. "Silicone hydrogel contact lenses" refers to contact lenses that include a silicone hydrogel body (core) material.

[0028] As used in this article, the term "soft contact lens" refers to a contact lens with an elastic modulus (i.e., Young's modulus) of less than 2.5 MPa.

[0029] As used herein, the term “hydrogel” or “hydrogel material” refers to a cross-linked polymer material having a three-dimensional polymer network (i.e., a polymer matrix) that is insoluble in water but can retain at least 10% by weight of water in its polymer matrix when fully hydrated (or in equilibrium).

[0030] As used herein, the term "siloxane hydrogel" refers to a siloxane-containing hydrogel obtained by copolymerization of a polymerizable composition comprising at least one siloxane-containing monomer or at least one siloxane-containing macromonomer or at least one crosslinkable siloxane-containing prepolymer.

[0031] As used in this article, the term "hydrophilic" describes a material or a portion thereof that will associate with water more readily than lipids.

[0032] As used in this article, the term "room temperature" refers to a temperature of approximately 21°C to approximately 27°C.

[0033] As used herein, the term "polymer" means a material formed by polymerizing / crosslinking one or more monomers or macromonomers or prepolymers or combinations thereof.

[0034] As used herein, the term “oxygen permeability (Dk)” refers to corrected oxygen permeability (Dkc), which is measured at approximately 34°C–35°C and corrected for surface tolerance to oxygen flux caused by boundary layer effects, according to the procedure described in Example 1 of U.S. Patent Application Publication No. 2012-0026457A1. Oxygen permeability is conventionally expressed in barrers, where “barrers” is defined as [(cm²)]. 3 Oxygen (mm) / (cm) 2 (s)(mmHg)]×10 -10 .

[0035] As used herein, the term "oxygen transmittance" Dk / t refers to the rate at which oxygen passes through a specific lens or material of average thickness t [in mm] over a measured area. Oxygen transmittance is conventionally expressed in barrers / mm, where "barrers / mm" is defined as [(cm 3 oxygen) / (cm 2 (s)(mmHg)]×10 -9 .

[0036] As used herein, the term "modulus" or "elastic modulus" refers to the tensile modulus or Young's modulus as a measure of stiffness of a contact lens or material. Those skilled in the art are well aware of how to determine the elastic modulus of a silicone hydrogel material or contact lens. For example, all commercial contact lenses have reported elastic modulus values.

[0037] As used herein, the term “average water contact angle” refers to the water contact angle obtained by averaging measurements from individual contact lens or silicone hydrogel material samples (measured by sessile drop).

[0038] As used herein, the term “UVA” refers to radiation occurring at wavelengths between 315 and 380 nanometers; “UVB” refers to radiation occurring between 280 and 315 nanometers; and “violet light” refers to radiation occurring at wavelengths between 380 and 440 nanometers.

[0039] As used in this article, “containing,” “having,” or “including” includes “containing,” “mainly composed of,” “substantially composed of,” and “composed of”; “mainly composed of,” “substantially composed of,” and “composed of” are subordinate concepts of “containing,” “having,” or “including.”

[0040] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, and the reagents, methods and equipment used are conventional reagents, methods and equipment in this technical field.

[0041] Example 1: Preparation of contact lenses #1 1. Preparation of tetrahedral PEG-siloxane hybrid macromonomer: 1.00 g (0.0001 mol) of four-arm PEG-NH2 (Mn 10 kDa) was mixed with 2.00 g (0.4 mol) of NHS-PDMS (Mn 5 kDa). 0.48-0.8 mmol of triethylamine was added to promote the reaction. The reaction was carried out at 21-25 °C for 12-24 hours with monitoring (sampling was performed using TLC, and the amine signal was detected by GPC or NMR after sampling). PEG-CONH-PDMS was precipitated with cold diethyl ether, washed 2-3 times, and dried to obtain the product TAPEG-PDMS, β1.05. The structure is as follows. Figure 1 As shown.

[0042] The simplified reaction formula is: PEG-NH+PDMS-NHS→PEG-CONH-PDMS+NHS.

[0043] 2. Preparation of the second monomer: After reacting the four-armed PEG-NHS (Mn 10kDa) with propargyl-amine, it was click-coupled with azido-PEG (Mn 5kDa).

[0044] The simplified reaction formula is: PEG-OCO-NHS+HC≡C-CH2-NH2→PEG-NH-CO-CH2-C≡CH+NHS; PEG-NH-CO-CH2-C≡CH+N3-PEG→PEG-NH-CO-CH2-triazole-PEG.

[0045] 3. Preparation of contact lenses: The two monomers mentioned above were prepared into 120 mg / mL solutions. - ¹, solutions with pH 7.2 to 7.4, after being mixed in equal volumes, were allowed to gel at room temperature for 2 to 5 minutes.

[0046] Structure as Figure 2 As shown in the figure, a distinct bicontinuous phase structure is visible: the bright area is the PEG-rich phase (hydrophilic channels), and the dark area is the PDMS-rich phase (hydrophobic / oxygen-permeable channels).

[0047] Example 2: Preparation of contact lenses #2 1. Preparation of tetrahedral PEG-siloxane hybrid macromonomer: Four-arm PEG-NH2 (Mn 10kDa) was reacted with NHS-TRIS (Mn 5kDa) at room temperature and purified to obtain TAPEG-TRIS, 1.05.

[0048] The simplified reaction formula is: PEG-NH+TRIS-NHS→PEG-CONH-TRIS+NHS.

[0049] 2. Preparation of the second monomer: TNPEG-alkyne (i.e., PEG-NH-CO-CH2-C≡CH).

[0050] 3. Preparation of contact lenses: The two monomers mentioned above were prepared into 120 mg / mL solutions. - ¹, solutions with pH 7.2 to 7.4, after being mixed in equal volumes, were allowed to gel at room temperature for 2 to 5 minutes.

[0051] Performance tests were conducted on contact lenses (commercially available silicone hydrogels: silicone oxoalkane hydrogels A (Dk 60 barrer, 24% water content) and B (Dk 80 barrer, 33% water content)). The results are shown in Table 1. Table 1

[0052] Stress-strain curves as follows Figure 3 As shown, the modulus is 2.1 MPa, indicating high stiffness and good strength; the shape of the curve in the figure indicates that the material has good ductility and toughness.

[0053] The three-dimensional performance diagram of oxygen permeability coefficient-moisture content-modulus is shown below. Figure 4 As shown, increasing the PDMS content usually increases Dk but decreases hydrophilicity (water content), while increasing the PEG content increases water content but decreases Dk. This invention achieves a compatibility zone of high Dk (>60 barrer), high water content (>40%) and suitable modulus (1~3 MPa) through a tetrahedral structure and a phase-separated bicontinuous network (highlighted areas in the figure).

[0054] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0055] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A tetrahedral PEG-siloxane hybrid macromonomer, characterized in that, It has the structure shown in equation (I); PEGm–X–(Si-arm)n Formula (I), Where X represents a carbamate, amide, or click chemical linker; Si-arm is selected from TRIS and / or PDMS; m and n are natural numbers selected from 1 to 99.

2. The tetrahedral PEG-siloxane hybrid macromonomer according to claim 1, characterized in that, X is an amide.

3. The tetrahedral PEG-siloxane hybrid macromonomer according to claim 1, characterized in that, The Si-arm is a PDMS.

4. The tetrahedral PEG-siloxane hybrid macromonomer according to claim 1, characterized in that, The m is selected from 4 and / or n is selected from 4.

5. The tetrahedral PEG-siloxane hybrid macromonomer according to any one of claims 1-4, characterized in that, The structure of the tetrahedral PEG-siloxane hybrid macromonomer is PEG4-CONH-PDMS4.

6. The tetrahedral PEG-siloxane hybrid macromonomer according to claim 5, characterized in that, The molecular weight of the TRIS and / or PDMS is 1~10 kDa.

7. The tetrahedral PEG-siloxane hybrid macromonomer according to claim 5, characterized in that, The molecular weight of the PEG is 8~12kDa.

8. The application of the tetrahedral PEG-siloxane hybrid macromonomer according to any one of claims 1 to 7 in the preparation of contact lenses.

9. A contact lens, characterized in that, Contains the tetrahedral PEG-siloxane hybrid macromonomer as described in any one of claims 1 to 7.

10. The contact lens according to claim 9, characterized in that, The contact lens also contains a second monomer, which contains clickable functional groups that are complementary to the tetrahedral PEG-siloxane hybrid macromolecular monomer.

11. The contact lens according to claim 10, characterized in that, The tetrahedral PEG-siloxane hybrid macromonomer and the second monomer are arranged alternately.

Images