A method for preparing a hydrogel based on the hofmeister effect and use in color-changing contact lenses

Abstract

The application discloses a hydrogel preparation method based on Hofmeister effect and application in color-changing contact lenses, and comprises the following steps: mixing a blue oxidation state 3,3',5,5'-tetramethyl benzidine solution with an agarose solution, rapidly reacting through microwave, mold pressing and cooling to form a blue contact lens; uniformly coloring the prepared blue contact lens with Hofmeister salt through simple drop or soaking method; and cleaning the colored contact lens. The color-changing contact lens prepared by the preparation method effectively avoids the high production cost and the safety problem of uneven lenses caused by using printing coloring technology, breaks through the fixed limitation that the color of the existing color contact lens cannot be changed once produced, and provides a novel color-changing mechanism and a reliable color-changing method for the current color-changing contact lens market.

Description

Technical Field

[0001] This invention belongs to the field of contact lens technology, specifically relating to a method for preparing hydrogels based on the hofmeister effect and their application in photochromic contact lenses. Background Technology

[0002] In recent years, the market size of contact lenses has been increasing year by year due to their convenience. Among them, colored contact lenses have been widely favored, accounting for a consistently high percentage of sales. People's expectations for contact lenses have also risen from the basic function of correcting vision to include cosmetic tools and trendy items that enhance a sense of technology. Therefore, there is an urgent need to develop more innovative colored contact lenses to meet market demands.

[0003] Currently, most methods used in the industry to manufacture colored contact lenses employ printing technologies such as pad printing and laser printing to print colors onto the surface of the contact lens. This coloring method has high manufacturing costs, requires high operational skills, and the printed color layer has a certain thickness, which may cause a foreign body sensation when wearing the lens. Furthermore, existing methods usually limit the optical properties of the contact lens during manufacturing, such as color, which cannot be changed once production begins. This hinders the aesthetic and functional flexibility of contact lenses. Summary of the Invention

[0004] Purpose of the invention: To address the problems existing in the prior art, this invention provides a method for preparing photochromic contact lenses based on the Hofmeister effect. This invention proposes a novel method for preparing photochromic contact lenses, which can effectively change color, solving the problem that it is difficult to change the color of contact lenses once they are produced on the market.

[0005] The present invention also provides photochromic contact lenses prepared by the aforementioned preparation method.

[0006] Technical Solution: To achieve the above objectives, the present invention provides a method for preparing photochromic contact lenses based on the Hofmeister effect, the method comprising the following steps:

[0007] Step 1: Place a uniformly mixed precursor formulation solution into the mold; the precursor formulation solution is blue oxidized 3,3',5,5'-tetramethylbenzidine (TMB). ox A mixture of solution with agarose, silica hydrogel, or methyl methacrylate;

[0008] Step two: Through microwave rapid reaction, mold pressing and cooling are used to form blue colored contact lenses;

[0009] Step 3: The prepared blue contact lens is mixed with hofmeister salt and the color is uniformly changed by simple dripping or soaking.

[0010] Step 4: Clean the discolored contact lenses.

[0011] The color change process is due to a change in the molecular structure of the precursor, which causes the absorption peak to shift, resulting in a stable color.

[0012] In step (1), for every 3 mL of liquid blue oxidized 3,3',5,5'-tetramethylbenzidine (TMBox) solution, 70-80 mg of agarose, silica hydrogel, or methyl methacrylate should be added. ox The specific molecular structure is an electron transfer complex of 3,3',5,5'-tetramethylbenzidine parent (TMB) and 3,3',5,5'-tetramethylbenzidine (TMB2+) with two positive charges.

[0013] As a preferred option, agarose is used in step (1).

[0014] In step (2), the microwave method involves placing 2-3 ml of the mixed solution in a microwave oven and heating it on high for 30 to 60 seconds, then switching to medium heat for another 30 to 60 seconds.

[0015] As a preferred option, the above-mentioned high flame is 700W and the medium flame is 500W.

[0016] In step (3), the cations that make up the hofmeister salt include: NH4 + Na + K + Li + Mg 2+ Ca 2+ Any one of them, including anions such as HPO4. 2- SO4 2- acetate - citrate - ,Cl - NO3 2- ClO4 - I - SCN - Any one of the above; the above cations and anions can be freely combined, wherein there is no specific requirement for the concentration of cations, and the concentration of anions is 500 μM.

[0017] In step (3), the hofmeister salt is a liquid-dissociated salt, which includes Cl. - NO3 2- ClO4 - I - SCN -Any of the ions. Hofmeister salts can alter the molecular structure of TMBox, causing a shift in the absorption peak position, thereby generating a stable color.

[0018] In step (3), the blue contact lens is placed in the hofmeister salt solution by dripping or soaking. Specifically, it is soaked in the hofmeister salt solution with a concentration not higher than 500 μM for no more than 1 minute, or 50-100 μL of hofmeister salt with a concentration not higher than 10 mmol is added and left to stand for no more than 1 minute.

[0019] Preferably, the solution is soaked in a 500 μM hofmeister salt solution for 1 minute, or 50-100 μL (2-3 drops) of 10 mmol hofmeister salt is added and allowed to stand for 1 minute.

[0020] In step (3), the color change time is within one minute after the addition or soaking of hofmeister salt. The characteristic is that the color change is rapid and uniform, and is closely related to the concentration of hofmeister salt.

[0021] In step (4), the solvent used for cleaning is PBS solution, and soaking and cleaning two to three times is sufficient.

[0022] The method for preparing photochromic contact lenses based on the Hofmeister effect described in this invention produces colored contact lenses with a novel color-changing mechanism.

[0023] The present invention describes the application of hofmeister salt in the preparation of photochromic contact lenses.

[0024] This invention relates to photochromic contact lenses based on the Hofmeister effect. By simply adding or soaking a prepared blue contact lens with Hofmeister salt, rapid and uniform color change can be achieved. Density functional theory calculations show that the color-changing principle of this invention is that the intervention of the Hofmeister anion alters the molecular structure of the precursor, shifting the absorption peak and producing a stable purple color. Contact toxicity experiments confirm the practicality of this invention. Therefore, photochromic contact lenses prepared using the above-described method of this invention effectively avoid the high manufacturing costs and safety issues associated with printing and coloring techniques, as well as lens unevenness. They eliminate the need for the instruments and precise operations required for printing and coloring; a dropper is sufficient, making the process easy for anyone to perform. This overcomes the inherent limitation of existing colored contact lenses, where the color cannot be changed once produced, providing the current photochromic contact lens market with a novel color-changing mechanism and a reliable color-changing method.

[0025] Based on the unique interaction between the electron transfer complex TMBox molecule and the hofmeister salt, this invention presents a novel method for color-changing contact lenses after the color has been fixed. Utilizing a novel color-changing mechanism, it is possible to achieve color-changing of colored contact lenses after the color has been fixed.

[0026] The hofmeister effect is an important phenomenon in biology, describing the interaction between proteins and salts. Salts that can alter protein stability are called hofmeister salts. This invention discovers that TMBox molecules exhibit a similar hofmeister effect to protein molecules in solution; that is, after the addition of hofmeister salt, TMBox molecules exhibit a precipitation sequence similar to that of protein molecules. For the first time, when the system was confined to a gel, the precipitation showed a uniform color change. The key to this color change lies in three aspects: firstly, the staining molecule TMBox, which cannot be achieved with other staining agents such as indigo or methylene blue; secondly, the type and concentration of the hofmeister salt, which is mainly related to the anion; and thirdly, the presence of hydrophobic anions (such as I)... - The addition of this method results in better performance and lower biotoxicity; salt concentrations below 500 μM can cause rapid discoloration. Thirdly, it utilizes a confined system; this invention uses an agarose system, but it should be noted that other matrix contact lens materials should also be applicable.

[0027] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0028] This invention utilizes the unique interaction between hofmeister anions and TMBox to achieve rapid and uniform color change in contact lenses. This color-changing method is simple to operate, and color change can be achieved by adding hofmeister salt after manufacturing. It provides a novel color-changing mechanism and a reliable color-changing method for the current photochromic contact lens market, and has broad application prospects.

[0029] The present invention has a novel overall method and low cost, breaking through the current situation that the color of colored contact lenses cannot be changed once they are manufactured. Attached Figure Description

[0030] Figure 1 This is a flowchart of the method for preparing photochromic contact lenses according to the present invention.

[0031] Figure 2 The images show actual contact lenses: (a) a light blue TMBox contact lens; and (b) a purple color-changing contact lens after the addition of hofmeister salt.

[0032] Figure 3(a) Color change of contact lenses after adding 100μM-500μM hofmeister salt (specifically potassium iodide salt); (b) Color change process of contact lenses within 1 minute after adding 500μM hofmeister salt (from blue to light purple to dark purple).

[0033] Figure 4 (a) The TMBox molecular structure optimized by DFT theoretical calculations, specifically the TMB parent structure and the TMB... 2+ (a) Charge-transfer complex structure; (b) TMBox molecular structure after the introduction of iodide ions; (c) UV absorption spectra of structures a and b calculated and simulated by density functional theory.

[0034] Figure 5 For in vitro toxicity and safety assessment of lenses. Detailed Implementation

[0035] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0036] Unless otherwise specified, all materials and reagents used in the following examples are commercially available. Experimental methods not specifically described in the examples are generally performed under standard conditions or as recommended by the manufacturer.

[0037] Instruments: Covered crucible mold, microwave oven (M1-L213B, 2.45GHz, Midea, China).

[0038] Materials: Oxidized 3,3',5,5'-tetramethylbenzidine (TMBox) solution, agarose.

[0039] Preparation of oxidized 3,3',5,5'-tetramethylbenzidine (TMBox) solution: 50 mmol of 3,3',5,5'-tetramethylbenzidine (TMB) was added to 100 mL of acetate-sodium acetate buffer solution containing 0.2 mol, and the solution was irradiated under a xenon lamp at 310 nm for 20 minutes to obtain pale blue oxidized TMBox.

[0040] Example 1

[0041] The specific steps for fabricating photochromic contact lenses based on the Hofmeister effect are as follows:

[0042] (1) Add 3 ml of a light blue oxidized 3,3',5,5'-tetramethylbenzidine (TMBox) and 75 mg of agarose solution to the bottom of a covered crucible mold and mix well;

[0043] (2) Place the mold in a microwave oven and heat on high (700W) for 30 to 60 seconds, then reduce to medium (500W) for another 30 to 60 seconds. Quickly remove the mold, cover and press to release air bubbles and allow to cool. After cooling for ten minutes, unmold and remove the light blue contact lens TMBox. See the image below. Figure 2 As shown in (a).

[0044] The physical property test results of the TMBox contact lens are shown in Table 1. The appearance test involved visually observing whether the lens surface was uniformly colored. In the test results, O indicates uniform coloring, and X indicates uneven coloring. The color fading test involved immersing the light blue TMBox contact lens of this embodiment in water for 2 hours, and then wiping the lens with a cotton swab to test for color fading. In the test results, O indicates no color fading was observed, and X indicates observed color fading. As shown in Table 1, within the observation period, the contact lens exhibited uniform coloring and no color fading.

[0045] Table 1 TMB ox Physical property testing of contact lenses

[0046] Observation time 0 hours 2 hours 4 hours 6 hours 8 hours Appearance test O O O O O Color fading test O O O O O

[0047] The above statements indicate that neither the colored contact lenses nor the photochromic contact lenses containing hofmeister salts showed any color leakage. Safety testing.

[0048] Example 2

[0049] Preparation of color-changing contact lenses

[0050] 1. Materials: TMBox contact lens (prepared in Example 1), hofmeister salt (the cations of which include: NH4+) + Na + K + Li + Mg 2+ Ca 2+ Anions include HPO4. 2- SO4 2- acetate - citrate - ,Cl - NO3 2- ClO4 - I - SCN - wait)

[0051] 2. Method:

[0052] (1) Take the TMBox contact lens prepared in Example 1 above, soak it in water, add hofmeister salt, soak it in 500μM NaI solution, let it stand for one minute, and you will get a purple contact lens.

[0053] (2) The purple contact lenses were transferred to PBS solution (pH 7.4) and soaked and washed twice to obtain the finished product, as shown in the figure below. Figure 2 As shown in (b).

[0054] 3. The physical property test results of the light purple contact lens are shown in Table 2. The appearance test involved visually observing whether the lens surface was uniformly colored. In the test results, O indicates uniform coloring, and X indicates uneven coloring. The color fading test involved immersing the purple lens prepared in this embodiment in water for 2 hours, and then wiping the lens with a cotton swab to test for color fading. In the test results, O indicates no color fading was observed, and X indicates observed color fading. As shown in Table 2, within the observation period, the contact lens showed uniform coloring and no color fading.

[0055] Table 2 Physical Properties Tests of Light Purple Contact Lenses

[0056] Observation time 0 hours 2 hours 4 hours 6 hours 8 hours Appearance test O O O O O Color fading test O O O O O

[0057] As can be seen from the above embodiments, rapid color change can be achieved by utilizing the special interaction between TMBox molecules and hofmeister salt, and the color will not easily fade. The present invention uses agarose-based contact lens material. It should be noted that other matrix contact lens materials should also be applicable.

[0058] Example 3

[0059] Example 3 uses the same method as Example 2, except that the hofmeister salt NaI is replaced with KI.

[0060] Example 4

[0061] Example 4 used the same method as Example 2, except that the concentration of the hofmeister salt NaI added was 100 μM-500 μM. The results were as follows. Figure 3 As shown, Figure 3 As can be seen, the purple color changes from light to dark as the salt concentration increases (counterclockwise from 11 o'clock). Therefore, by controlling the salt concentration, contact lenses with different shades of purple can be obtained. Figure 3 b shows the color change within 10-60 seconds after adding 500 μM hofmeister salt (counterclockwise from 9 o'clock).

[0062] Example 5

[0063] In this invention, the color-changing principle is that the intervention of the hofmeister anion alters the molecular structure of the precursor, shifting the absorption peak and thus producing stable alternative colors. For example... Figure 4 As shown, for the hofmeister salt anion (I) in Examples 2 and 3 - Density functional theory calculations were performed on the TMBox molecule (the purple sphere in the image represents an iodine ion) and the TMBox molecule. All calculations were performed using Gaussian 16 software. Figure 4 Figure a uses the M062X functional combined with the 6–31g(d) basis set. Figure 4 Figure b uses the M062X functional combined with the def2tzvp basis set. (Comparison) Figure 4 a and Figure 4 The simulated optimized structure of b reveals that the aromatic ring plane of the TMBox molecule undergoes a certain angle flip after the introduction of iodide ions. Figure 4 Simulations of the ultraviolet spectrum show that the ultraviolet spectrum of the structure shifts after the introduction of iodine ions, thus exhibiting a color change.

[0064] Example 6

[0065] The stained purple lenses prepared in Example 2 were soaked overnight in PBS (pH 7.4) buffer solution to obtain the purple lens extract. Human ovarian cancer cells (SKOV-3) were cultured for 24 h in a medium containing 90% DMEM and 10% fetal bovine serum. The cells were then transferred to the purple lens extract and incubated at 37°C with 5% CO2 for 1 h, 4 h, and 6 h, respectively. Then, all the medium was removed, and 200 μL of fresh medium and 20 μL of MTT solution (5 mg / mL) were added. Incubation continued for 4 h, the medium containing MTT was removed, and 150 μL of DMSO solution was added. Finally, the absorbance at 492 nm was recorded using a microplate reader. Cell viability was calculated as follows:

[0066] Cell viability = (Absorbance of leachate - Absorbance of background group) / (Absorbance of control group without sample leachate - Absorbance of background group) × 100%.

[0067] result Figure 5 As shown, cytotoxicity and safety studies were conducted. After co-incubating the lens extract of the present invention with cells for 6 hours, there was no significant adverse effect on the cells, demonstrating its good biocompatibility.

[0068] Comparative Example 1

[0069] Using the method in Example 1, replacing the TMBox molecule with a common dye, such as methylene blue or indigo, and adding hofmeister salt according to the method in Example 2, no color change was achieved.

Claims

1. A method for preparing photochromic contact lenses based on the Hofmeister effect, characterized in that, The method includes the following steps: Step (1): Place a uniformly mixed precursor formulation solution in a mold; the precursor formulation solution is blue oxidized 3,3',5,5'-tetramethylbenzidine (TMB). ox A mixture of solution and agarose; Step (2): Through microwave rapid reaction, mold pressing and cooling are used to form a blue colored contact lens; Step (3): The prepared blue contact lens is soaked with hofmeister salt to uniformly change its color; Step (4): Clean the discolored contact lens; In step (3), the hofmeister salt is a liquid-dissociated salt, and its anion is I. - The soaking refers to immersing in a hofmeister salt solution with a concentration not exceeding 500 μM for no more than 1 minute.

2. The method for preparing photochromic contact lenses based on the Hofmeister effect according to claim 1, characterized in that, In step (1), the precursor formulation solution contains 3 mL of TMB per 3 mL. ox Add 70-80 mg of agarose to the solution, including TMB. ox The specific molecular structure is an electron transfer complex of 3,3',5,5'-tetramethylbenzidine parent compound and 3,3',5,5'-tetramethylbenzidine with two positive charges.

3. The method for preparing photochromic contact lenses based on the Hofmeister effect according to claim 1, characterized in that, In step (2), the microwave method involves placing 2-3 ml of the mixed solution in a microwave oven and heating it on high for 30 to 60 seconds, then switching to medium heat for another 30 to 60 seconds.

4. The method for preparing photochromic contact lenses based on the Hofmeister effect according to claim 1, characterized in that, In step (4), the cleaning solvent is PBS solution, and soaking and cleaning two to three times is sufficient.

5. A colored contact lens with a color-changing mechanism prepared by the method for preparing a photochromic contact lens based on the Hofmeister effect as described in claim 1.

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