OPHTHALMIC GEL, AND MANUFACTURING PROCESS THEREFOR

Abstract: An improved injectionable viscoelastic gel for use in ophthalmic surgical and treatment procedures, wherein the gelling agent is a high molecular weight polyacrylamide or polymethacrylamide. The present application is a continuation-in-part ap­ plication of Serial No. 434,412, filed October 14, 1982.

Description: 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. Positiely, 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 instances, 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 non-reactive 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 and correctional treatment of bullous rhegmatogenous retinal detachment. These and other objects will become apparent from the disclosure which follows. In accordance with the present invention, there is provided an improved viscoelastic gel comprising: In this paritcularly effective formulation, it has been found that the effectiveness thereof is achieved by compounding the constituents thoreof within certain, well-defined ranges and by employing polyacrylamides and polymethacrylamides of certain, well-defined molecular weiqhts. The polyacrylamides found to be effective in the present compositions are polymer having a molecular weight of from 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 5 million from 4.5 to 5.5 million. Inclusion of the polymer in the gel formulation is maintained within from 2 to 5 percent by weights, preferably from 3.5 to 4.5 percent by weight, and most preferably 4.0 percent by weight. The remaining constituents of the formulation are present in the following amounts, based upon percent by weight: A particularly suitable formulation consisting of 4.0 percent by weight polymer gel having a molecular weight of 5 million; 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 up to 100°C 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 examples serve 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: 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: The gel, when utilized in standard testing for biocompatibility and irritation determinations, produced no adverse reactions in the ocular tissues of the test animals.

Claims: An injectionable viscoelastic gel particularly adapted for use in ophthalmic surgical procedures and treatments which gel comprises from 2 to 5 percent by weight of a polymer selected from polyacrylamide and polymethacrylamide, said polymer having a molecular weight of from 1 to 6 million; from 0.4 to 8.6 percent by weight sodium chloride, from 0.075 to 0.3 percent by weight potassium chloride, from 0.04 to 0.33 percent by weight calcium chloride,, from 0.02 to 0.04 percent by, weight magnesium chloride hexahydrate, from 0.3 to 0.4 percent by weight sodium acetate, from 0.15 to 0.20 percent by weight of a buffer, remainder water. A gel as defined in claim 1 wherein said polymer is polyacrylamide. A gel as defined in claim 1 wherein said polymer is present in an amount of from 3.5 to 4.5 percent by weight. A gel as defined in claim 1 wherein said polymer has a molecular weight of from 4.5 to 5.5 million. A gel as defined in claim 1 wherein said buffer is sodium citrate dihydrate. A gel as defined in claim 1 consisting of 4 percent by weight of said polymer having a molecular weight of 5 million, 0.49 percent by weight sodium chloride, 0.075 percent by weight potassium chloride, 0.048 percent by weight calcium chloride, 0.03 percent by weight magnesium chloride hexahydrate, 0.17 percent by weight sodium citrate dihydrate, remainder water. A process for producing an injectionable viscoelastic gel particularly adapted for use in ophthalmic surgical procedures and treatments which comprise: admixing. a polymer of molecular weight 1 to 6 million with water, said polymer being selected from polyacrylamide and polymethacrylamide, to provide an admixture of from 8 to 10 percent by weight of the polymer, heating said admixture at sterilization temperatures of up to 100°C; and thereafter, admixing said admixture with an aqueous pre-formed salt solution to provide a gel containing from 2 to 5 percent by weight polymer; from 0.4 to 8.6 percent by weight sodium chloride; from 0.075 to 0.3 percent by weight potassium chloride; from 0.04 to 0.33 percent by weight calcium chloride; from 0.02 to 0.04 percent by weight magnesium chloride hexahydrate; from 0.3 to 0.4 percent by weight sodiun acetate, from 0.15 to 0.20 percent by weight of a buffer, remainder water.

Inventors: CHYLINSKI, VICTORIA S., TRAGER, SEYMOUR F.
Applicants: CHYLINSKI, VICTORIA S., TRAGER, SEYMOUR F.
Application year: 1984
Main classification: A61K47
IPC codes: A61L27, A61K9, A61K31, A61F9