Polydimethylsiloxane for intraocular filling material and preparation method thereof

Abstract

The invention relates to polydimethylsiloxane for an intraocular filling material and a preparation method thereof, and the preparation method comprises the following steps: (1) mixing a cyclosiloxane monomer, an end-capping reagent and a catalyst, and reacting under the conditions of normal pressure and 80-105 DEG C to obtain a reaction product; the mass ratio of the cyclosiloxane monomer to the end-capping reagent is 100: (0.5-2); (2) removing the catalyst and residual monomers in the reaction product to obtain a crude product; and (3) carrying out purification treatment on the crude product to obtain the polydimethylsiloxane. The preparation raw materials and the process steps are designed, so that the obtained polydimethylsiloxane has the characteristics of high purity, few residual monomers and difficulty in emulsification, and can be directly used as an intraocular filling material.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical production, and in particular relates to polydimethylsiloxane used as an intraocular filling material and a preparation method thereof. Background Art

[0002] Intraocular fillers, also known as vitreous cavity replacements, are non-solid surgical implants placed within the vitreous cavity of the eye. They are used during ophthalmic surgery to flatten and reattach a detached retina to the retinal pigment epithelium (RPE), or to support and fix the retina. As such, intraocular fillers should be colorless and transparent, have a refractive power close to that of the vitreous, be chemically stable, have a pH close to that of the intraocular environment, allow for long-term intraocular retention, be non-toxic and non-irritating, and have good tissue compatibility.

[0003] As a colorless, transparent, odorless, non-toxic oily liquid, polydimethylsiloxane has excellent physiological inertness, is non-degenerative in tissues, is non-carcinogenic, and has biological tolerance. It can also prevent intraoperative bleeding and inhibit the growth and contraction of fibrous membranes, making it an excellent choice as a long-lasting intraocular filling material. The high interfacial tension between polydimethylsiloxane and water can effectively prevent water from entering the subretinal space through retinal tears, thereby closing retinal tears and maintaining retinal fixation. As an inert intraocular filling material, polydimethylsiloxane has unique stability and safety among the optional fillers for vitreoretinal surgery, has a high surgical success rate, and is widely favored by doctors and patients. With the advent of an aging society and the improvement of domestic medical diagnosis and treatment levels, vitreous eye surgery will become more common, and accordingly, the demand gap for polydimethylsiloxane for ophthalmic surgery will also expand.

[0004] Polydimethylsiloxane (PDMS) used clinically is typically in concentrations ranging from 1000 cst to 5000 cst, with 2000 cst and 5000 cst silicone oils being the predominant. While 2000 cst PDMS is widely used in vitreoretinal surgery, there is currently no method for directly preparing PDMS suitable for intraocular filling materials. Clinically, mixtures of PDMS with varying viscosities are used, resulting in poor product homogeneity and a high incidence of emulsification. Industrial synthesis methods, which mostly rely on hydrolysis of chlorosilanes or strong acid- and base-catalyzed siloxane polycondensation, are complex, corrosive, and require difficult catalyst post-processing. These methods also place high demands on monomer purity. Even 100 μL / L of impurities such as SiCl₄, MeSiCl₃, and MeHSiCl₂ can severely impact product performance, and residual catalysts can compromise product intraocular safety. Using safe, low-toxic raw materials for the direct preparation and purification of PDMS is crucial to improving its performance and reducing the incidence of clinical complications associated with emulsification. Therefore, there is an urgent need to design a preparation method for polydimethylsiloxane that can be directly used as an intraocular filling material. Summary of the Invention

[0005] In response to the shortcomings of the prior art, the present invention aims to provide a polydimethylsiloxane for use as an intraocular filling material and a method for preparing the same. By designing the raw materials and process steps, a polydimethylsiloxane with high purity, low residual monomer content, and low emulsification resistance can be obtained, which can be directly used as an intraocular filling material.

[0006] To achieve this object, the present invention adopts the following technical solutions:

[0007] In a first aspect, the present invention provides a method for preparing polydimethylsiloxane for intraocular filling materials, the preparation method comprising the following steps:

[0008] (1) mixing a cyclosiloxane monomer, a capping agent, and a catalyst, and reacting the mixture under normal pressure and 80-105° C. to obtain a reaction product; wherein the mass ratio of the cyclosiloxane monomer to the capping agent is 100:(0.5-2);

[0009] (2) removing the catalyst and residual monomers in the reaction product to obtain a crude product;

[0010] (3) Purifying the crude product to obtain the polydimethylsiloxane.

[0011] The preparation method of polydimethylsiloxane provided by the present invention directly mixes cyclosiloxane monomer, end-capping agent and catalyst for reaction in a one-pot process, resulting in a mild reaction and a simple synthetic route. The prior art generally dehydrates the raw materials before reacting, and the reaction is usually carried out under a nitrogen atmosphere, and even requires decompression for reaction. However, the preparation method of polydimethylsiloxane provided by the present invention does not require any pretreatment of the raw materials. All the raw materials are directly reacted after mixing. The reaction conditions are mild, without harsh temperature, pressure and other conditions, and the reaction route is simple. This achieves the purpose of preparing polydimethylsiloxane through extremely simple steps. In addition, the obtained polydimethylsiloxane has high purity, low residual monomers, is not easy to emulsify, and can be directly used as an intraocular filling material.

[0012] The reaction temperature is 80-105°C, for example, 80°C, 82°C, 85°C, 88°C, 90°C, 92°C, 95°C, 98°C, 100°C, 102°C, 105°C, etc.

[0013] The mass ratio of the cyclosiloxane monomer to the end-capping agent is 100:(0.5-2), for example, it can be 100:0.5, 100:0.6, 100:0.7, 100:0.8, 100:0.9, 100:1, 100:1.1, 100:1.2, 100:1.3, 100:1.4, 100:1.5, 100:1.6, 100:1.7, 100:1.8, 100:1.9, 100:2, etc.

[0014] The following are preferred technical solutions of the present invention, but are not intended to limit the technical solutions provided by the present invention. Through the following preferred technical solutions, the objectives and beneficial effects of the present invention can be better achieved and realized.

[0015] As a preferred technical solution, the cyclosiloxane monomer includes hexamethylcyclotrisiloxane and / or octamethylcyclotetrasiloxane.

[0016] Preferably, the capping agent includes any one of hexamethyldisiloxane, decamethyltetrasiloxane or tetradecamethylhexasiloxane, or a combination of at least two thereof.

[0017] Preferably, the catalyst comprises tetrabutylphosphonium hydroxide and / or tetramethylammonium hydroxide.

[0018] In the present invention, the catalyst used can decompose by itself after the reaction is completed, thereby solving the problems of severe corrosion and difficulty in post-processing of the catalyst caused by using strong acids and strong bases as catalysts.

[0019] Preferably, the mass ratio of the cyclosiloxane monomer to the catalyst is 100:(0.05-0.15), for example, it can be 100:0.05, 100:0.06, 100:0.07, 100:0.08, 100:0.09, 100:0.1, 100:0.11, 100:0.12, 100:0.13, 100:0.14, 100:0.15, etc.

[0020] Preferably, the reaction time is 8-16 h, for example, 8 h, 8.5 h, 9 h, 9.5 h, 10 h, 10.5 h, 11 h, 11.5 h, 12 h, 12.5 h, 13 h, 13.5 h, 14 h, 14.5 h, 15 h, etc.

[0021] Preferably, in step (2), the catalyst is removed by raising the temperature of the reaction product to 135-170°C (for example, 135°C, 138°C, 140°C, 142°C, 145°C, 148°C, 150°C, 152°C, 155°C, 158°C, 160°C, 162°C, 165°C, 168°C, 170°C, etc.).

[0022] Preferably, the removal of the residual monomers in step (2) is carried out at a temperature of 135-170°C (for example, 135°C, 138°C, 140°C, 142°C, 145°C, 148°C, 150°C, 152°C, 155°C, 158°C, 160°C, 162°C, 165°C, 168°C, 170°C, etc.) and a vacuum degree of <-0.07 MPa (for example, -0.07 MPa, -0.075 MPa, -0.08 MPa, -0.085 MPa, -0.09 MPa, -0.095 MPa, -0.1 MPa, etc.).

[0023] Preferably, the purification method comprises the following steps:

[0024] (S1) injecting the crude product into a first molecular distillation device for a first purification to obtain a purified intermediate;

[0025] (S2) injecting the purified intermediate into a second molecular distillation device for a second purification to obtain the polydimethylsiloxane.

[0026] The present invention abandons the traditional purification methods of extraction, adsorption and atmospheric distillation and introduces efficient molecular distillation equipment. In the short-path evaporator, the scraping system evenly distributes the material on the heated inner wall of the evaporator, making the purification process more streamlined and efficient.

[0027] Preferably, the feed rate of the crude product and the discharge rate of the purified intermediate in step (S1) are each independently 2-4 kg / h, for example, 2 kg / h, 2.2 kg / h, 2.4 kg / h, 2.6 kg / h, 2.8 kg / h, 3 kg / h, 3.2 kg / h, 3.4 kg / h, 3.6 kg / h, 3.8 kg / h, 4 kg / h, etc.

[0028] Preferably, the first purification is carried out under a vacuum degree of 1-2 mbar, for example, 1 mbar, 1.05 mbar, 1.1 mbar, 1.15 mbar, 1.2 mbar, 1.25 mbar, 1.3 mbar, 1.35 mbar, 1.4 mbar, 1.45 mbar, 1.5 mbar, 1.55 mbar, 1.6 mbar, 1.65 mbar, 1.7 mbar, 1.75 mbar, 1.8 mbar, 1.85 mbar, 1.9 mbar, 1.95 mbar, 2 mbar, etc.

[0029] Preferably, the first purification is carried out at 160-220°C, for example, 160°C, 165°C, 170°C, 175°C, 180°C, 185°C, 190°C, 195°C, 200°C, 205°C, 210°C, 215°C, 220°C, etc.

[0030] Preferably, the feeding rate of the purified intermediate and the discharging rate of the polydimethylsiloxane in step (S2) are each independently 1-2 kg / h, for example, 1 kg / h, 1.05 kg / h, 1.1 kg / h, 1.15 kg / h, 1.2 kg / h, 1.25 kg / h, 1.3 kg / h, 1.35 kg / h, 1.4 kg / h, 1.45 kg / h, 1.5 kg / h, 1.55 kg / h, 1.6 kg / h, 1.65 kg / h, 1.7 kg / h, 1.75 kg / h, 1.8 kg / h, 1.85 kg / h, 1.9 kg / h, 1.95 kg / h, 2 kg / h, etc.

[0031] Preferably, the second purification is carried out at a vacuum degree of <1×10 -2 The pressure may be adjusted to 0.05 mbar, 0.06 mbar, 0.07 mbar, 0.008 mbar, 0.009 mbar, etc.

[0032] Preferably, the second purification is carried out at 220-280°C, for example, 220°C, 225°C, 230°C, 235°C, 240°C, 245°C, 250°C, 255°C, 260°C, 265°C, 270°C, 275°C, 280°C, etc.

[0033] Preferably, the preparation method specifically comprises the following steps:

[0034] (1) mixing a cyclosiloxane monomer, a capping agent, and a catalyst, and reacting the mixture under normal pressure and 80-105° C. for 8-16 hours to obtain a reaction product; the mass ratio of the cyclosiloxane monomer to the capping agent is 100:(0.5-2); the mass ratio of the cyclosiloxane monomer to the catalyst is 100:(0.05-0.15);

[0035] (2) raising the temperature of the reaction product to 135-170° C. to remove the catalyst, and then removing the residual monomers at a temperature of 135-170° C. and a vacuum degree of less than -0.07 MPa to obtain a crude product;

[0036] (3) injecting the crude product into a first molecular distillation device at a rate of 2-4 kg / h, and performing a first purification under the conditions of a vacuum degree of 1-2 mbar and a temperature of 160-220° C. to obtain a purified intermediate, wherein the discharge rate of the purified intermediate is 2-4 kg / h;

[0037] The purified intermediate was injected into the second molecular distillation equipment at a rate of 1-2 kg / h and the vacuum degree was less than 1×10 - 2 mbar and a temperature of 220-280° C. to perform a second purification to obtain the polydimethylsiloxane, with a discharge rate of 1-2 kg / h.

[0038] In a second aspect, the present invention provides a polydimethylsiloxane for use as an intraocular filling material, wherein the polydimethylsiloxane is prepared using the preparation method described in the first aspect.

[0039] Preferably, the viscosity of the polydimethylsiloxane is 1600-2400 cst, for example, it can be 1600 cst, 1650 cst, 1700 cst, 1750 cst, 1800 cst, 1850 cst, 1900 cst, 1950 cst, 2000 cst, 2050 cst, 2100 cst, 2150 cst, 2200 cst, 2250 cst, 2300 cst, 2350 cst, 2400 cst, etc.

[0040] In the present invention, the viscosity of polydimethylsiloxane is tested using the Pinnacle capillary viscometer method specified in General Chapter 0633 of the Pharmacopoeia of the People's Republic of China, Part IV.

[0041] Preferably, the refractive index of the polydimethylsiloxane is 1.40-1.41, for example, it may be 1.401, 1.402, 1.403, 1.404, 1.405, 1.406, 1.407, 1.408, 1.409, etc.

[0042] In the present invention, the refractive index test method is the refractive index determination method of General Chapter 0622 of the Pharmacopoeia of the People's Republic of China, Volume IV, with a measuring temperature of 35±2° C. and a wavelength of 589±10 nm.

[0043] Preferably, the volatility of the polydimethylsiloxane is less than 0.1%, for example, it may be 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, etc.

[0044] Preferably, the impurity content in the polydimethylsiloxane is less than 100 ppm, for example, it can be 0.5 ppm, 5 ppm, 10 ppm, 15 ppm, 20 ppm, 25 ppm, 30 ppm, 35 ppm, 40 ppm, 45 ppm, 50 ppm, 55 ppm, 60 ppm, 65 ppm, 70 ppm, 75 ppm, 80 ppm, 85 ppm, 90 ppm, 95 ppm, etc.

[0045] In the present invention, impurities in polydimethylsiloxane refer to unreacted cyclosiloxane monomers, end-capping agents, reaction by-products, and the like.

[0046] The numerical range described in the present invention includes not only the point values listed above, but also any point values between the above numerical ranges that are not listed. Due to space limitations and for the sake of simplicity, the present invention no longer exhaustively lists the specific point values included in the range.

[0047] Compared with the prior art, the present invention has the following beneficial effects:

[0048] (1) The preparation method provided by the present invention has a simple synthetic route and mild reaction conditions, without harsh temperature, pressure and other conditions, which provides a strong guarantee for achieving process repeatability and product quality stability;

[0049] (2) The polydimethylsiloxane prepared by the preparation method provided by the present invention has high purity, low residual monomers, suitable dispersibility, is not easy to emulsify, has fewer side effects on patients, has good biocompatibility, can reduce the probability of postoperative complications, and can also reduce the surgical challenges of polydimethylsiloxane implantation and removal. DETAILED DESCRIPTION

[0050] For the convenience of understanding the present invention, the present invention is given below with examples. It should be understood by those skilled in the art that the examples are only for the purpose of helping to understand the present invention and should not be regarded as specific limitations of the present invention.

[0051] Example 1

[0052] A polydimethylsiloxane for intraocular filling material and a preparation method thereof, the preparation method comprising the following steps:

[0053] (1) 30 kg of octamethylcyclotetrasiloxane, 30 g of tetramethylammonium hydroxide, and 420 g of hexamethyldisiloxane were mixed, and the mixture was reacted under normal pressure and 80° C. for 16 h under stirring to obtain a reaction product;

[0054] (2) heating the reaction product to 135° C. to inactivate tetramethylammonium hydroxide, and then removing residual monomers at 135° C. and −0.085 MPa to obtain a crude product;

[0055] (3) injecting the crude product into a first molecular distillation device for the first purification, setting the heating temperature to 160° C., the vacuum degree to 1 mbar, the feed rate and the discharge rate to 2 kg / h, to obtain a purified intermediate;

[0056] The purified intermediate was injected into the second molecular distillation equipment for the second purification, and the heating temperature was set to 220 ° C and the vacuum degree was 2×10 -3 mbar, and the feed rate and the discharge rate were both 1 kg / h to obtain the polydimethylsiloxane.

[0057] Example 2

[0058] A polydimethylsiloxane for intraocular filling material and a preparation method thereof, the preparation method comprising the following steps:

[0059] (1) 3000 g of hexamethylcyclotrisiloxane, 4.5 g of tetrabutylphosphine hydroxide, and 15 g of decamethyltetrasiloxane were mixed, and the mixture was reacted under normal pressure and 95° C. for 12 h under stirring to obtain a reaction product;

[0060] (2) heating the reaction product to 155° C. to inactivate tetrabutylphosphonium hydroxide, and then removing residual monomers at 155° C. and −0.09 MPa to obtain a crude product;

[0061] (3) injecting the crude product into a first molecular distillation device for the first purification, setting the heating temperature to 200° C., the vacuum degree to 1.5 mbar, the feed rate and the discharge rate to 3 kg / h, to obtain a purified intermediate;

[0062] The purified intermediate was injected into the second molecular distillation equipment for the second purification, and the heating temperature was set to 250 ° C and the vacuum degree was 5×10 -3 mbar, and the feed rate and the discharge rate were both 1.5 kg / h to obtain the polydimethylsiloxane.

[0063] Example 3

[0064] A polydimethylsiloxane for intraocular filling material and a preparation method thereof, the preparation method comprising the following steps:

[0065] (1) 3000 g of octamethylcyclotetrasiloxane, 4.5 g of tetramethylammonium hydroxide, and 60 g of tetradecamethylhexasiloxane were mixed, and the mixture was reacted under normal pressure and 105° C. for 8 h to obtain a reaction product;

[0066] (2) heating the reaction product to 170° C. to inactivate tetramethylammonium hydroxide, and then removing residual monomers at 170° C. and −0.075 MPa to obtain a crude product;

[0067] (3) injecting the crude product into a first molecular distillation device for the first purification, setting the heating temperature to 220° C., the vacuum degree to 2 mbar, the feed rate and the discharge rate to 4 kg / h, to obtain a purified intermediate;

[0068] The purified intermediate was injected into the second molecular distillation equipment for the second purification, and the heating temperature was set to 280 ° C and the vacuum degree was 1×10 -3 mbar, and both the feed rate and the discharge rate were 2 kg / h to obtain the polydimethylsiloxane.

[0069] Example 4

[0070] A polydimethylsiloxane for intraocular filling material and a preparation method thereof, which differs from Example 1 only in that the amount of hexamethyldisiloxane used in step (1) is 300 g, and the remaining raw materials, process parameters and steps are the same as those in Example 1.

[0071] Example 5

[0072] A polydimethylsiloxane for intraocular filling material and a preparation method thereof, which differs from Example 1 only in that the amount of hexamethyldisiloxane used in step (1) is 220 g, and the remaining raw materials, process parameters and steps are the same as those in Example 1.

[0073] Comparative Example 1

[0074] A polydimethylsiloxane for intraocular filling material and a preparation method thereof, the preparation method comprising the following steps:

[0075] (1) 200 g of octamethylcyclotetrasiloxane and tetramethylammonium hydroxide crystals were added to a reaction vessel at a mass ratio of 50:1, and stirred at 65° C. under reduced pressure for 4 h to obtain tetramethylammonium hydroxide siliconate;

[0076] (2) 30 kg of octamethylcyclotetrasiloxane, 420 g of hexamethyldisiloxane and 1530 g of the tetramethylammonium hydroxide siliconate were added to a reaction vessel, heated to 50° C. and stirred for 2 h under nitrogen protection, then heated to 80° C. and reacted at −0.04 MPa for 16 h to obtain a reaction product;

[0077] (3) heating the reaction product to 135° C. to inactivate tetramethylammonium hydroxide siliconate, and then removing residual monomers at 135° C. and −0.085 MPa to obtain a crude product;

[0078] (4) injecting the crude product into a first molecular distillation device for the first purification, setting the heating temperature to 160° C., the vacuum degree to 1 mbar, the feed rate and the discharge rate to 2 kg / h, to obtain a purified intermediate;

[0079] The purified intermediate was injected into the second molecular distillation equipment for the second purification, and the heating temperature was set to 220 ° C and the vacuum degree was 2×10 -3 mbar, and the feed rate and the discharge rate were both 1 kg / h to obtain the polydimethylsiloxane.

[0080] Comparative Example 2

[0081] A polydimethylsiloxane for intraocular filling material and a preparation method thereof, which differs from Example 1 only in that the reaction temperature in step (1) is 75°C, and the remaining raw materials, process parameters and steps are the same as those in Example 1.

[0082] Comparative Example 3

[0083] A polydimethylsiloxane for intraocular filling material and a preparation method thereof, which differs from Example 1 only in that the reaction temperature in step (1) is 110°C, and the remaining raw materials, process parameters and steps are the same as those in Example 1.

[0084] Comparative Example 4

[0085] A polydimethylsiloxane for intraocular filling material and a preparation method thereof, which differs from Example 1 only in that the amount of hexamethyldisiloxane used in step (1) is 650 g, and the remaining raw materials, process parameters and steps are the same as those in Example 1.

[0086] Comparative Example 5

[0087] A polydimethylsiloxane for intraocular filling material and a preparation method thereof, which differs from Example 1 only in that the amount of hexamethyldisiloxane used in step (1) is 140 g, and the remaining raw materials, process parameters and steps are the same as those in Example 1.

[0088] Product parameters and performance testing

[0089] (1) Viscosity: Tested in accordance with the Pinnacle capillary viscometer method in General Chapter 0633 of the Pharmacopoeia of the People's Republic of China, Part IV.

[0090] (2) Refractive index: The test was conducted in accordance with the refractive index determination method in General Chapter 0622 of the Pharmacopoeia of the People's Republic of China, Volume IV, with a measurement temperature of 35±2°C and a wavelength of 589±10nm.

[0091] (3) Volatility:

[0092] Place the constant-weight vessel on an analytical balance and weigh it. Then add 2±0.01g of sample and weigh the total amount. Place the sample in an electric drying oven at 150℃±2℃ and bake for 2h. After taking it out, place it in a desiccator and cool it to room temperature. Weigh it and calculate the volatility according to the following formula:

[0093]

[0094] Where:

[0095] ω—mass fraction of volatile matter in the sample, expressed in %;

[0096] m2—the total mass of the sample and the container before baking, in g;

[0097] m3—the total mass of the sample and the container after baking, in g;

[0098] m1—mass of the container, in g.

[0099] (4) Impurity content:

[0100] Weigh about 0.5g of polydimethylsiloxane into a 10mL centrifuge tube, add 4mL of n-hexane, shake thoroughly to dissolve it, dilute to 5mL with n-hexane, filter with a filter membrane, and use the filtrate as the test solution. Take the above test solution for injection testing (chromatographic conditions: HP-5 capillary column; injection port temperature 250℃; detector: FID (Agilent 7820A)), substitute it into the standard curve and calculate the content of each impurity by external standard method. Substitute the peak area of the test sample corresponding to the retention time into the standard curve to calculate the concentration c of each impurity in the test sample. i , use the following formula to calculate the total content of impurities in the sample.

[0101]

[0102] Where:

[0103] C—total content of impurities in the sample, μg / g;

[0104] c i —The mass concentration of impurity i calculated from the calibration curve, μg / mL;

[0105] V—the constant volume of the sample, mL;

[0106] m—mass of the sample, g.

[0107] The polydimethylsiloxanes provided in Examples 1-5 and Comparative Examples 1-5 were tested according to the above method. The test results are shown in Table 1:

[0108] Table 1

[0109] Viscosity (cst) Refractive index Volatility (%) Impurity content (ppm) Example 1 1648 1.4048 0.02 10 Example 2 2311 1.4051 0.02 8 Example 3 2026 1.4043 0.08 12 Example 4 2085 1.4030 0.02 9 Example 5 2296 1.4030 0.06 16 Comparative Example 1 1670 1.4054 0.05 4 Comparative Example 2 1452 1.4048 0.06 6 Comparative Example 3 2833 1.4055 0.03 14 Comparative Example 4 1200 1.4030 0.02 18 Comparative Example 5 4400 1.4030 0.06 16

[0110] As can be seen from the test data in Table 1, the polydimethylsiloxane prepared by the preparation method provided by the present invention has low volatility of 0.02-0.08%, uniform viscosity of 1648-2311 cSt, impurity content far less than 100 ppm, and a refractive index of 1.4030-1.4051. As an intraocular filling material, its viscosity and refractive index properties meet the requirements of clinical use at home and abroad.

[0111] Although qualified polydimethylsiloxane was also prepared in Comparative Example 1, the reaction needed to be carried out under nitrogen atmosphere and reduced pressure, and the preparation conditions were more stringent.

[0112] It can be seen from Comparative Examples 2-3 that the reaction temperature in step (1) is too low, the reaction polymerization degree is low, and the viscosity of the obtained polydimethylsiloxane is low, which does not meet the requirements for clinical use; the reaction temperature is too high, exceeding the boiling point of the capping agent, and the capping agent is easily lost during the reaction, resulting in the actual amount of capping agent participating in the reaction being lower than expected, which in turn leads to the viscosity of the polydimethylsiloxane being too high, which does not meet the requirements for clinical use.

[0113] As can be seen from Comparative Example 4, if the mass ratio of the cyclosiloxane monomer to the end-capping agent is too small, the viscosity of the polydimethylsiloxane obtained by the reaction is too low, which does not meet the requirements for clinical use; as can be seen from Comparative Example 5, if the mass ratio of the cyclosiloxane monomer to the end-capping agent is too large, the viscosity of the polydimethylsiloxane is too high, which does not meet the requirements for clinical use.

[0114] The applicant declares that the present invention uses the above-described embodiments to illustrate the detailed process equipment and process flow of the present invention. However, the present invention is not limited to the above-described detailed process equipment and process flow, and does not necessarily rely on the above-described detailed process equipment and process flow in order to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent replacements for the raw materials of the present invention's products, additions of auxiliary ingredients, and selection of specific methods, etc., fall within the scope of protection and disclosure of the present invention.

Claims

1. A method for preparing polydimethylsiloxane for intraocular filling material, characterized in that: The preparation method comprises the following steps: (1) mixing a cyclosiloxane monomer, a capping agent, and a catalyst, and reacting the mixture under normal pressure and 80-105° C. to obtain a reaction product; wherein the mass ratio of the cyclosiloxane monomer to the capping agent is 100:(0.5-2); (2) removing the catalyst and residual monomers in the reaction product to obtain a crude product; (3) Purifying the crude product to obtain the polydimethylsiloxane.

2. The preparation method according to claim 1, characterized in that The cyclosiloxane monomers include hexamethylcyclotrisiloxane and / or octamethylcyclotetrasiloxane; Preferably, the end-capping agent comprises any one of hexamethyldisiloxane, decamethyltetrasiloxane or tetradecamethylhexasiloxane, or a combination of at least two thereof; Preferably, the catalyst comprises tetrabutylphosphonium hydroxide and / or tetramethylammonium hydroxide.

3. The preparation method according to claim 1 or 2, characterized in that The mass ratio of the cyclosiloxane monomer to the catalyst is 100:(0.05-0.15).

4. The preparation method according to any one of claims 1 to 3, characterized in that The reaction time is 8-16h; Preferably, in step (2), the catalyst is removed by raising the temperature of the reaction product to 135-170° C.; Preferably, the removal of the residual monomers in step (2) is carried out at a temperature of 135-170° C. and a vacuum degree of less than -0.07 MPa.

5. The preparation method according to any one of claims 1 to 4, characterized in that The purification method comprises the following steps: (S1) injecting the crude product into a first molecular distillation device for a first purification to obtain a purified intermediate; (S2) injecting the purified intermediate into a second molecular distillation device for a second purification to obtain the polydimethylsiloxane.

6. The preparation method according to claim 5, characterized in that The feed rate of the crude product and the discharge rate of the purified intermediate in step (S1) are each independently 2-4 kg / h; Preferably, the first purification is carried out under a vacuum degree of 1-2 mbar; Preferably, the first purification is carried out at 160-220°C.

7. The preparation method according to claim 5 or 6, characterized in that: The feed rate of the purified intermediate and the discharge rate of the polydimethylsiloxane in step (S2) are each independently 1-2 kg / h; Preferably, the second purification is carried out at a vacuum degree of <1×10 -2 mbar; Preferably, the second purification is carried out at 220-280°C.

8. The preparation method according to any one of claims 1 to 7, characterized in that The preparation method specifically comprises the following steps: (1) mixing a cyclosiloxane monomer, a capping agent, and a catalyst, and reacting them at normal pressure and 80-105° C. for 8-16 hours to obtain a reaction product; The mass ratio of the cyclosiloxane monomer to the end-capping agent is 100:(0.5-2); the mass ratio of the cyclosiloxane monomer to the catalyst is 100:(0.05-0.15); (2) raising the temperature of the reaction product to 135-170° C. to remove the catalyst, and then removing the residual monomers at a temperature of 135-170° C. and a vacuum degree of less than -0.07 MPa to obtain a crude product; (3) injecting the crude product into a first molecular distillation device at a rate of 2-4 kg / h, and performing a first purification under the conditions of a vacuum degree of 1-2 mbar and a temperature of 160-220° C. to obtain a purified intermediate, wherein the discharge rate of the purified intermediate is 2-4 kg / h; The purified intermediate was injected into the second molecular distillation equipment at a rate of 1-2 kg / h and the vacuum degree was less than 1×10 - 2 mbar and a temperature of 220-280° C. to perform a second purification to obtain the polydimethylsiloxane, with a discharge rate of 1-2 kg / h.

9. A polydimethylsiloxane for intraocular filling material, characterized in that: The polydimethylsiloxane is prepared by the preparation method according to any one of claims 1 to 8.

10. The polydimethylsiloxane according to claim 9, characterized in that The viscosity of the polydimethylsiloxane is 1600-2400 cst; Preferably, the refractive index of the polydimethylsiloxane is 1.40-1.41; Preferably, the volatility of the polydimethylsiloxane is less than 0.1%; Preferably, the impurity content in the polydimethylsiloxane is less than 100 ppm.

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