Abstract:
This invention relates to the preparation of vinyl carbonate capped polydimethylsiloxanes. More specifically, the invention relates to the preparation of vinyl carbonate capped polydimethylsiloxanes for use in forming optically clear medical devices by the ring opening siloxane rearrangement polymerization using water content standardized cation exchange resins as the catalytic species.

Description:
FIELD  
       [0001]     This invention relates to the preparation of vinyl carbonate capped polydimethylsiloxanes. More specifically, the invention relates to the preparation of vinyl carbonate capped polydimethylsiloxanes for use in forming optically clear medical devices by the ring opening siloxane rearrangement polymerization using water content standardized cation exchange resins as the catalytic species.  
       BACKGROUND  
       [0002]     V 2 D 25  (RD352) is a siloxane cross-linker used in the production of medical devices. The chemical structure of V 2 D 25  is provided below:  
                         
 
 Presently, the synthesis of RD352 involves a triflic acid catalyzed ring opening polymerization of octamethylcyclotetrasiloxane with a vinyl carbonate butylcapped tetramethyldisiloxane. One of the major problems with this synthetic route is that an intense black color forms immediately following the addition of the triflic acid catalyst. The species responsible for the color has not been identified. The removal of this color requires several lengthy and expensive decolorization steps. Despite these efforts to decolorize the RD352 prepared by triflic acid catalyst ring opening polymerization, the color, in fact, is never fully removed. The final product, after the decolorization steps, is a yellow to orange fluid. In addition to the color problem of the prior art reaction, it has been determined that a portion of the vinyl carbonate end-cap degrades during the ring-opening step resulting in a non-polymerizable by-product. 
 
         [0003]     Therefore, the problem addressed by the invention herein is that current methods of making monomers such as RD352 for use in preparing optically clear medical devices results in materials having a dark color and non-polymerizable by products. Although the dark color may be minimized by the use of additional decolorization steps, it would be desirable to provide a method of synthesizing monomers for use in preparing optically clear medical devices that results in a clear monomer product.  
         [0004]     Ring-opening polymerization of orgnopolysiloxanes is known. For example, U.S. Pat. No. 5,504,234 to Omura et al. discloses a method for the preparation of a (meth)acryloxyalkyl group-containing organopolysiloxane having a linear structure by the ring-opening siloxane rearrangement polymerization reaction of a (meth)acryloxyalkyl group-containing cyclic organopolysiloxane oligomer either alone or in combination with a cyclic organopolysiloxane oligomer having no (meth)acryloxyalkyl groups. Different from conventional acidic catalyst, the reaction can be promoted by the use of a cation-exchange resin in the H +  form which can be readily removed from the polymerization mixture after completion of the polymerization reaction leaving no acidic matter which influences on the stability of the product. The catalytic efficiency of the cation-exchange resin can be further enhanced when the resin is, prior to contacting with the cyclic organopolysiloxane oligomer(s), impregnated or swollen with a polar organic solvent such as tetrahydrofuran. The Omura patent does not standardize the water content of the ion-exchange resins used and the synthesis is run at an elevated temperature of 60° C.  
         [0005]     Therefore, there is still a need to provide a reaction mechanism that provides the desired monomer in good yield and of optically clear quality for the production of optically clear medical devices.  
       SUMMARY  
       [0006]     Provided herein are methods of forming monomers for use in forming medical devices. The method consists of extracting the ion-exchange resin first with a polar solvent such as THF followed by washing with a 0.5% N HCl and distilled water to achieve acidic pH. The washed and acidified resin is then dried, for instance in a vacuum oven, until 100% solids is obtained. The dried resin along with 10% by weight water (based on the weight of the resin) is then added to a reaction vessel containing octamethylcyclotetrasiloxane and vinyl carbonate capped disiloxane at a concentration to yield a desired statistical chain length. The contents of the reaction vessel are stirred vigorously at room temperature for about 96 hours followed by filtration to remove the ion-exchange resin. The final product is an optically clear viscous fluid. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0007]      FIG. 1  is a gas chromatogram of the distillate from a thin film evaporator used to purify monomer prepared according to the prior art;  
         [0008]      FIG. 2  is a gas chromatogram of the distillate from a thin film evaporator used to purify monomer prepared according to the method of the invention herein.  
     
    
     DESCRIPTION  
       [0009]     As is described above, the most characteristic feature in the inventive method consists in the use of a water content standardized cation-exchange resin in the acidified form (i.e., normalized) as a catalyst for the ring-opening siloxane rearrangement polymerization reaction of the cyclic organopolysiloxane oligomer or oligomers in place of conventional acids as an acidic catalyst. After completion of the polymerization reaction, the cation-exchange resin can be easily removed from the reaction mixture by filtration leaving an organopolysiloxane product that can be used in the manufacture of medical devices. Such medical devices would include contact lenses, phakic intraocular lenses, aphakic intraocular lenses, corneal implants, etc.  
         [0010]     The method of the present invention is basically a ring-opening siloxane rearrangement polymerization reaction of a cyclic organopolysiloxane oligomer such as an octamethylcyclotetrasiloxane as the component (a), and an end capped disiloxane such as vinylcarbonate capped disiloxane as component (b). When a mixture of the oligomers (a) and (b) is subjected to the polymerization reaction, the weight proportion of component (a) should be at least about 75% based on the amount of the mixture since, when the proportion of the component (a) is too small, the linear organopolysiloxane obtained as the product has no particular functional merit over conventional diorganopolysiloxanes such as dimethyl polysiloxanes containing no vinyl carbonate functional groups.  
         [0011]     The above mentioned cyclic organopolysiloxane oligomer as the component (a) is typically a cyclic oligomer (D4) expressed by the formula:  
                         
 
         [0012]     The above mentioned end capped disiloxane oligomer (V2) as the component (b) is typically expressed by the formula:  
                         
 
         [0013]     In step (A) of the inventive method, the above described cyclic organopolysiloxane oligomer or oligomers are (a and b) blended with a cation-exchange resin in the water standardized acidic form as the component (c) to give a polymerization mixture.  
         [0014]     The cation-exchange resin used as component (c) is decolorized and cleaned and standardized to a desired level of water content (i.e., normalized) prior to combining with components (a) and (b). The desired level of water content serves to control the relative amount of monofunctionality of the end product. The first step in preparing the standardized resin is to decolorize the resin. This is achieved through washing the ion-exchange resin with any suitable resin expanding solvent such as THE, polar solvents, acetyl nitrile, toluene, etc. The selection of a suitable resin expanding solvent is within the purview of one of ordinary skill in the art. Preferred solvents are HPLC grade to avoid the introduction of undesired materials into the standardized resins. After decolorizing, the resin is then cleaned with high purity water and dried to constant weight. After drying, the resin is washed with mineral acid solution such as 0.5N HCl to remove any unbound acids. The resin is then washed with high purity water until the wash water is acidic. This indicates that any unbound acids have been removed. The resin is then dried again to provide the activated resin. After activation of the resin, an amount of water is added to the resin to control the degree of water content of the resin. Controlling the degree of water content of the resin allows one to control the amount of mono-functional product. The controlled degree of water content of the resin is what is meant as “water content standardized resin” or words of similar import.  
         [0015]     It was also determined that the glassware used in performing the resin activation and standardization procedure should be cleaned with Aqua Regia prior to performing the resin activation and standardization procedure. This cleaning step removes any silicone stopcock grease as well as any trace of the Alcoholic KOH normally used to wash laboratory glassware. Acetone is used for the final rinse step of the glassware used in the resin activation and standardization procedure.  
         [0016]     Various grades of commercial products of dry-type cation-exchange resins are available on the market and can be used in the resin activation and standardizing procedure including Amberlyst 15 E Dry manufactured by Rohm &amp; Haas Co. and Purolites CT-165, CT-169, CT-171DR and CT-175 manufactured by Purolite Co.  
         [0017]     The amount of the above described cation-exchange resin in the polymerization mixture is in the range from about 5 to about 15% by weight or, preferably, from about 3 to about 5% by weight based on the amount of the cyclic organopolysiloxane oligomer or oligomers. When the amount of the cation-exchange resin is too small, the velocity of the polymerization reaction cannot be high enough as a matter of course while, when the amount thereof is too large, a substantial amount of the diorganopolysiloxane product adheres to the resin particles and cannot be recovered resulting in a decrease in the product yield with no particular additional advantages in the velocity of polymerization or in other respects.  
         [0018]     Besides the above described cyclic organopolysiloxane oligomer or oligomers, the polymerization mixture is admixed with an oligomeric diorganopolysiloxane or, in particular, dimethyl polysiloxane terminated at each molecular chain end with a trimethyl silyl group or dimethyl (meth)acryloxyalkyl silyl group with an object to provide terminal groups to the linear diorganopolysiloxane product.  
         [0019]     The polymerization mixture prepared by mixing the above described ingredients is then, in step (B) of the inventive method, agitated at room temperature for a length of time, usually, in the range from about 4 to about 120 hours to effect the ring-opening polymerization of the cyclic oligomer or oligomers. In step (C) of the inventive method, thereafter, the linear diorganopolysiloxane thus formed in the reaction mixture is freed from the beads of the cation-exchange resin by filtration using, for example, a metal wire screen of suitable mesh openings. No particular difficulties are encountered in this filtration treatment.  
         [0020]     The cation-exchange resin recovered by separating from the polymerization mixture by filtration can be re-used as such in the next run of the polymerization reaction. It has been discovered that the catalytic activity of the thus recovered cation-exchange resin can be more fully regained by washing the resin beads separated from the polymerization mixture of the previous run with a polar organic solvent as completely as possible or, for example, with the polar organic solvent in an at least equal amount to the resin so that the resin is freed from the adhering organopolysiloxane. The organopolysiloxane dissolved away from the resin beads by washing can be recovered by removing the solvent from the washings under reduced pressure so that no decrease is caused in the yield of the product due to washing of the cation-exchange resin with a polar organic solvent.  
         [0021]     As shown in  FIG. 1 , monomer prepared according to the prior art method (triflic acid catalyst) contains high molecular weight materials removed by thin film evaporating.  FIG. 2  shows that monomer prepared according to the method of the invention herein contains fewer high molecular weight materials removable by thin film evaporation.  
         [0022]     Following, the method of the invention is described in more detail by way of examples, which, however, never limit the scope of the invention in any way. The Examples and Comparative Examples were prepared by combining the materials as described and allowing them to react at room temperature with agitation for 48 hours unless expressly stated otherwise. All numerical values should be considered to be modified by the term “about” unless specifically identified otherwise. Unless specified otherwise, in each example and comparative example 11.25 grams of V2, 50 grams of distilled D4 and 2.25 grams of resin was used. The product was then filtered and placed over solid sodium bicarbonate for two days. The product formed was vacuum stripped at 80° C. for about four hours and then weighed for yield and analyzed for Mn, Mw and polydispersity (Pd). Color of the final sample was determined by visual inspection. Mn is number average molecular weight determined by Gel Permeation Chromatography (GPC). Mw is weight average molecular weight determined by GPC. All resins were obtained from Sigma Aldrich.  
       EXAMPLES  
     Comparative Example 1  
     V2D25 Synthesis Using Ion Exchange Resin at Room Temperature  
       [0023]     CAS #39389-20-3 AMBERLYST 15 add 0.1 gram MeOH anhydrous to pot after resin V2 D4 added  
                                                           GPC                       (Yellow)   Mn   Mw   Pd                           Yield 9.9 grams   1437   2037   1.42                      
 
       Comparative Example 2  
     V2D25 Synthesis Using Ion Exchange Resin at Room Temperature  
       [0024]     CAS #39389-20-3 AMBERLYST 15 add 0.1 gram MeOH (anhydrous) to resin before V2 and D4 added  
                                                           GPC                       (yellow)   Mn   Mw   Pd                           Yield 10.8 grams   1500   2239   1.49                      
 
       Comparative Example 3  
     V2D25 Synthesis Using Ion Exchange Resin at Room Temperature  
       [0025]     CAS #39389-20-3 Amberlyst 15 add 0.1 gram DI water to pot after resin, V2, and D4 added  
                                                           GPC                       (Clear)   Mn   Mw   Pd                           Yield 13.1 grams   2792   5015   1.79                      
 
       Comparative Example 4  
     V2D25 Synthesis Using Ion Exchange Resin at Room Temperature  
       [0000]     3.68 grams V2  
         [0000]     16.32 grams distilled D4  
         [0000]     1.0 grams resin  
         [0026]     CAS #9037-24-5 AMBERLYST 15 95% solids No water added  
                                                           GPC   Mn   Mw   Pd                           24 hours   1736   2883   1.66           Filter at 96 hours   1954   3383   1.73           13.2 grams           (yield)                      
 
       Comparative Example 5  
     V2D25 Synthesis Using Ion Exchange Resin at Room Temperature  
       [0000]     3.68 grams V2  
         [0000]     16.32 grams distilled D4  
         [0000]     2.0 grams resin  
         [0027]     CAS #9037-24-5 AMBERLYST 15 RESIN # 1 95% solid  
                                                           GPC   Mn   Mw   Pd                            4 hours   1475   2194   1.49            8 hours   1771   2730   1.54           24 hours   1999   3363   1.68           48 hours   1915   3422   1.79           72 hours   2001   3609   1.80           96 hours   2015   3660   1.82           Filter at 96 hours   2027   3576   1.77           Yield 12.2 grams                      
 
       Comparative Example 6  
     V2D25 Synthesis Using Ion Exchange Resin at Room Temperature  
       [0000]     4.0 grams resin  
         [0028]     CAS #9037-24-5 AMBERLYST 15 RESIN #1 95% solids  
                                                                             Mn   Mw   Pd                                         4 hours   1774   2819   1.59            8 hours   1952   3179   1.63           24 hours   2144   3793   1.77           48 hours   2163   4089   1.89           72 hours   2289   4442   1.94           96 hours   2263   4404   1.95           Filter at 96 hours   2257   4407   1.96           Yield 10.5 grams                      
 
       Example 1  
     V2D25 Synthesis Using Ion Exchange Resin at Room Temperature  
       [0029]     CAS #39389-20-3 AMBERLYST 15 add 0.1 gram DI water to resin before V2 and D4 added  
                                                           GPC                       (Clear)   Mn   Mw   Pd                           Yield 13.5 grams   2831   5245   1.84                      
 
       Example 2  
     V2D25 Synthesis Using Ion Exchange Resin at Room Temperature  
       [0030]     CAS #39389-20-3 AMBERLYST 15 100% solids add 0.05 grams of water to the resin GPC  
                                                           GPC   Mn   Mw   Pd                           24 hours   1545   2302   1.49           Filter at 96 hours   2001   3335   1.67           12.9 grams (yield)                      
 
       Example 3  
     V2D25 Synthesis Using Ion Exchange Resin at Room Temperature  
       [0031]     AMBERLYST 15 dry 7-9291 100% solids add 0.05 grams of water to the resin  
                                                           GPC   Mn   Mw   Pd                           24 hours   1732   2932   1.69           Filter at 96 hours   1858   3244   1.75           14.6 grams (yield)                      
 
       Example 4  
     V2D25 Synthesis Using Ion Exchange Resin at Room Temperature  
       [0000]     3.68 grams V2  
         [0000]     16.32 grams distilled D4  
         [0000]     1.0 grams resin  
         [0032]     CAS #9037-24-5 AMBERLYST 15 RESIN #4 100% solids 0.05 grams water added  
                                                           GPC   Mn   Mw   Pd                           72 hours   1900   3452   1.82           96 hours   1904   3433   1.80           Filter at 96 hours   2033   3556   1.75           13.25 grams (yield)                      
 
       Example 5  
     V2D25 Synthesis Using Ion Exchange Resin at 60 C  
       [0000]     3.68 grams V2  
         [0000]     16.32 grams distilled D4  
         [0000]     1.0 grams resin  
         [0033]     AMBERLYST 15 RESIN 99.7% solids 0.05 grams water added  
                                                                       GPC                Mn   Mw   Pd                             2 hours   1515   2508   1.66            4 hours   1835   3108   1.69            6 hours   1675   2887   1.72            8 hours   2184   3852   1.76           16 hours   2718   4933   1.82           24 hours   3116   5732   1.84           Filter at 24 hours   3557   6450   1.81                         Yield 12.3 grams             
 
       Example 6  
     V2D25 Synthesis Using Normalized Ion Exchange Resin at Room Temperature  
       [0000]     3.68 grams V2  
         [0000]     16.32 grams distilled D4  
         [0000]     11.0 grams resin  
         [0034]     AMBERLYST 15 RESIN 99.7% solids 0.047 grams water added  
                                                                       GPC                Mn   Mw   Pd                            24 hours   1455   2089   1.44           48 hours   1791   2743   1.53           72 hours   2012   3184   1.58           96 hours   2064   3292   1.59           125 hours    2143   3600   1.68           165 hours    2276   3873   1.70                         Yield 10.51 grams             
 
       Example 7  
     V2D25 Synthesis Using Normalized Ion Exchange Resin at Room Temperature  
       [0000]     3.68 grams V2  
         [0000]     16.32 grams distilled D4  
         [0000]     2.0 grams resin Amberlyst15 Resin 99.7% solids  
         [0035]     AMBERLYST 15 RESIN 99.7% solids 0.094 grams water added  
                                                                       GPC                Mn   Mw   Pd                            24 hours   1827   2777   1.52           48 hours   2075   3427   1.65           72 hours   2320   3947   1.70           96 hours   2385   4155   1.74           125 hours    2444   4380   1.79           165 hours    2564   4553   1.78                         Yield 12.21 grams             
 
       Example 8  
     V2D25 Synthesis Using Normalized Ion Exchange Resin at Room Temperature  
       [0036]    
       
         
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                   
                   
               
               
                   
                   
               
               
                   
                 Mn 
                 Mw 
                 Pd 
                 D4/D5 
                 OH 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 24 hours 
                 2411 
                 4000 
                 1.66 
                 1.54 
                   
               
               
                   
                 48 hours 
                 2487 
                 4375 
                 1.76 
                 1.61 
               
               
                   
                 72 hours 
                 2104 
                 3789 
                 1.80 
                 1.46 
               
               
                   
                 96 hours 
                 2126 
                 3883 
                 1.83 
                 1.46 
               
               
                   
                 96 hours 
                 2044 
                 3731 
                 1.83 
                 0.67 
               
               
                   
                   
               
             
          
         
       
     
       Example 9  
     V2D25 Synthesis Using Normalized Ion Exchange Resin at Room Temperature  
       [0000]     3.68 grams V2  
         [0000]     16.32 grams distilled D4  
         [0000]     2.0 grams resin Amberlyst 15 Resin 99.7% solids  
         [0000]     Water added directly to resin before D4 and V2 added  
         [0037]     AMBERLYST 15 RESIN 99.7% solids 0.470 grams water added (25%)  
                                                                                             Mn   Mw   Pd   D4/D5   OH                                        24 hours   1768   2791   1.58   1.48               48 hours   1818   3046   1.68   1.50           72 hours   1835   3157   1.72   1.32           96 hours   1788   3127   1.75   1.58           96 hours   1733   3121   1.80   1.10                      
 
       Example 10  
     V2D25 Synthesis Using Normalized Ion Exchange Resin at Room Temperature  
       [0000]     3.68 grams V2  
         [0000]     16.32 grams distilled D4  
         [0000]     2.0 grams resin Amberlyst 15 Resin 99.7% solids  
         [0038]     Water added directly to resin before D4 and V2 added AMBERLYST 15 RESIN 99.7% solids 0.188 grams water added (10%)  
                                                                       Mn   Mw   Pd   D4/D5   OH                           24 hours   2289   3875   1.69   1.70               48 hours   1953   3454   1.77   1.54           72 hours   1964   3500   1.78   1.47           96 hours   1956   3504   1.80   1.48           96 hours   1925   3498   1.82   0.53                      
 
 Analysis 
 
         [0039]     The examples and comparative examples demonstrate the desirability of using a water content standardized (normalized) ion exchange resin to obtain a colorless product having the desired degree of polydispersity.  
         [0040]     The claims, as originally presented and as they may be amended, encompass variations, alternatives, modifications, improvements, equivalents, and substantial equivalents of the embodiments and teachings disclosed herein, including those that are presently unforeseen or unappreciated, and that, for example, may arise from applicants/patentees and others.