Patent Publication Number: US-RE32969-E

Title: Injectionable visoelastic ophthalmic gel

Description:
.Iadd.This is a continuation-in-part of Ser. No. 434,412, filed Oct. 14, 1982, now abandoned. .Iaddend. 
    
    
     BACKGROUND OF THE INVENTION 
     This invention relates to ophthalmic surgery and treatment. More particularly, this invention relates to a composition particularly suitable for use as an adjunct in ophthalmic surgery. 
     In surgical procedures involving ocular tissue such as, for example, anterior segment surgery, it is always necessary to protect the corneal endothelium from mechanical damage. Failure to provide adequate protection can result in irreparable damage to the tissue. 
     Presently, ophthalmic surgical procedures are carried out in a viscoelastic medium so as to prevent mechanical damage and denudation of the tissue surfaces. Sodium hyaluronate is currently widely used as the viscoelastic substance, presenting both positive and negative facets in ophthalmic surgical procedures. Positively, the hyaluronate has been reported as protecting the corneal endothelium; however, great care must be exercised in the use of hyaluronate, and in many instances, undesirable post-operative pressure increases have been noted, with dilation and, in some instance, adhesion development between the posterior capsule and the iris. 
     It is an object of the present invention to provide an improved injectionable ocular surgical and treatment adjunct. 
     It is a further object of the present invention to provide an improved injectionable viscoelastic solution which is nonreactive with ocular tissues. 
     A further object of the present invention is to provide an improved injectionable viscoelastic solution which may be employed without postoperative complications in such anterior segment surgical procedures as cataract removal, corneal transplants, penetrating keratoplasty, correctional treatment of bullous rhegmatogenous retinal detachment and the like. 
     These and other objects will become apparent from the disclosure which follows. 
     STATEMENT OF THE INVENTION 
     In accordance with the present invention, there is provided an improved viscoelastic gel comprising: 
     an acrylamide polymer selected from polyacrylamide and polymethacrylamide 
     sodium chloride 
     potassium chloride 
     calcium chloride 
     magnesium chloride hexahydrate 
     sodium acetate 
     buffer 
     water 
     In this particularly effective formulation, it has been found that the effectiveness thereof is achieved by compounding the constituents thereof within certain, well-defined ranges and by employing polyacrylamides and polymethacrylamides of certain, well-defined molecular weights. 
     The polyacrylamides found to be effective in the present compositions are polymers having a molecular weight of from about 1 to 6 million, produced by the polymerization of acrylamide, methacrylamide, or mixtures thereof by methods known to the art. Preferably, the polymers have a molecular weight on the order of about 5 million. Inclusion of the polymer in the gel formulation is maintained within from about 2 to about 5 percent by weights, preferably from about 3.5 to about 4.5 percent by weight, and most preferably about 4.0 percent by weight. 
     The remaining constituents of the formulation are present in the following amounts, based upon percent by weight: 
     
         ______________________________________                                    
sodium chloride  0.4-8.6                                                  
potassium chloride                                                        
                 0.075-0.3                                                
calcium chloride 0.04-0.33                                                
magnesium chloride                                                        
                 0.02-0.04                                                
hexahydrate                                                               
sodium acetate   0.3-0.4                                                  
buffer           0.15-0.20                                                
water            remainder                                                
______________________________________                                    
 
    
     A particularly suitable formulation is a 4.0 percent by weight polymer gel containing 0.49 percent by weight sodium chloride, 0.075 percent by weight potassium chloride, 0.048 percent by weight calcium chloride, 0.03 magnesium chloride hexahydrate and 0.17 sodium citrate dihydrate as the buffering agent. 
     While sodium citrate dihydrate is preferred as a gel buffer, other pharmaceutically acceptable buffering agents such as sodium phosphates and sodium borates may be advantageously employed. 
     The composition is formulated by autoclaving at sterilization temperatures an 8-10 percent by weight of the polymer and admixing the sterile gel with the premixed salt solution. It has been found that compounding of the polymer with the salt constituents prior to sterilization results in a rise in pH above an acceptable level. 
     The viscoelastic gels of the present invention are, as previously stated, particularly useful in ocular surgical procedures as a surgical adjunct, exhibiting: 
     (a) protective properties for corneal endothelium, iris and retinal tissue; 
     (b) superior properties as an aqueous humor replacement; 
     (c) ability to maintain a deep anterior chamber during operative procedures; 
     (d) ability to separate effectively tissue surfaces and thereby minimize adhesion; and 
     (e) biocompatibility with intra ocular tissues. 
     The particular effectiveness of this specific formulation as an adjunct in ophthalmic surgery is a direct result of its balanced viscoelastic properties. The viscous nature thereof provides mechanical protection for tissues (iris, retina) and cell layers (corneal endo- and epithelium) which may be exposed to mechanical damage during surgery. Further, due to the physical properties of the formulation, the gel does not flow out of the anterior chamber, providing a deep anterior chamber during surgical manipulations. 
    
    
     The following example serves to illustrate the present invention. 
     EXAMPLE 1 
     An autoclaved polyacrylamide having a molecular weight of about 5 million was admixed with a premixed salt solution to yield the following homogenous gel composition: 
     
         ______________________________________                                    
Component        Percent by Weight                                        
______________________________________                                    
polyacrylamide   4.0                                                      
sodium chloride  0.049                                                    
potassium chloride                                                        
                 0.075                                                    
calcium chloride 0.048                                                    
magnesium chloride                                                        
                 0.030                                                    
hexahydrate                                                               
sodium acetate   0.390                                                    
sodium citrate dihydrate                                                  
                 0.170                                                    
water            remainder                                                
______________________________________                                    
 
    
     The gel, when utilized in standard testing for biocompatibility and irritation determinations, produced no adverse reactions in the ocular tissues of the test animals. 
     EXAMPLE 2 
     An autoclaved polymethacrylate having a molecular weight of about 5 million was admixed with a premixed salt solution to yield the following homogenous gel composition: 
     
         ______________________________________                                    
Component        Percent by Weight                                        
______________________________________                                    
polymethacrylamide                                                        
                 4.0                                                      
sodium chloride  0.049                                                    
potassium chloride                                                        
                 0.075                                                    
calcium chloride 0.048                                                    
magnesium chloride                                                        
                 0.030                                                    
hexahydrate                                                               
sodium acetate   0.390                                                    
sodium citrate dihydrate                                                  
                 0.170                                                    
water            remainder                                                
______________________________________                                    
 
    
     The gel, when utilized in standard testing for biocompatibility and irritation determinations, produced no adverse reactions in the ocular tissues of the test animals.