Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUSRE32969 E
Publication typeGrant
Application numberUS 07/116,579
Publication dateJun 27, 1989
Filing dateAug 24, 1987
Priority dateOct 14, 1982
Fee statusPaid
Publication number07116579, 116579, US RE32969 E, US RE32969E, US-E-RE32969, USRE32969 E, USRE32969E
InventorsSeymour F. Trager, Victoria S. Chylinski
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Injectionable visoelastic ophthalmic gel
US RE32969 E
Abstract
An improved injectionable viscoelastic gel for use in opthalmic surgical and treatment procedures, wherein the gelling agent is a high molecular weight polyacrylamide or polymethacrylamide.
Images(4)
Previous page
Next page
Claims(9)
What is claimed is:
1. An injectionable viscoelastic gel particularly adapted for use in ophthalmic surgical procedures and treatments .[.which.]..Iadd., said .Iaddend.gel consisting essentially of from about 2 to about 5 percent by weight of a polymer selected from polyacrylamide and polymethacrylamide, said polymer having a molecular weight of from about 1 to about 6 million.[.;.]..Iadd., .Iaddend.from about 0.4 to about 8.6 percent by weight sodium chloride, from about 0.075 to about 0.3 percent by weight .[.postassium.]. .Iadd.potassium .Iaddend.chloride, from about 0.04 to about 0.33 percent by weight calcium chloride, from about 0.02 to about 0.04 percent by weight magnesium chloride hexahydrate, from about 0.3 to about 0.4 percent by weight sodium acetate, from about 0.15 to about 0.20 percent by weight of a buffer, remainder water.
2. A gel as defined in claim 1 wherein said polymer is polyacrylamide.
3. A gel as defined in claim 1 wherein said polymer is present in an amount of from about 3.5 to about 4.5 percent by weight.
4. A gel as defined in claim 1 wherein said polymer has a molecular weight of from about 4.5 to about 5.5 million.
5. A gel as defined in claim 1 wherein said buffer is sodium citrate dihydrate.
6. A gel as defined in claim 1 consisting essentially of about 4 percent by weight of said polymer having a molecular weight of about 5 million, about 0.049 percent by weight sodium chloride, about 0.075 percent by weight potassium chloride, about 0.048 percent by weight calcium chloride, about 0.03 percent by weight magnesium chloride hexahydrate, about 0.17 percent by weight sodium citrate dihydrate, remainder water. .Iadd.
7. A method for protecting ocular tissue during ophthalmic surgery which comprises
injecting into an ocular chamber prior to said surgery an amount of viscoelastic gel sufficient to prevent mechanical damage and denudation of said ocular tissue during said surgery, said viscoelastic gel comprising a polymer selected from polyacrylamide, polymethacrylamide and a copolymer of acrylamide and methacrylamide, said polymer having a molecular weight of from about 1 to 6 million, and a pharmaceutically acceptable diluent therefor. .Iaddend. .Iadd.8. The method of claim 7 wherein said surgical procedure is an anterior segment surgical procedure. .Iaddend. .Iadd.9. The method of claim 8 wherein said anterior segment surgical procedure is cataract removal, corneal transplant, keratoplasty or bullous
rhegmatogenous retinal detachment. .Iaddend. .Iadd.10. The method of claim 7 wherein said polymer is present in an amount between about 2 to about 5 percent by weight of said viscoelastic gel. .Iaddend. .Iadd.11. The method of claim 7 wherein said polymer is present in an amount between about 3.5 to about 4.5 percent by weight of said viscoelastic gel. .Iaddend. .Iadd.12. The method of claim 7 wherein said polymer is present in an amount between about 4.5 to about 5.5 percent by weight of said viscoelastic gel. .Iaddend. .Iadd.13. The method of claim 7 wherein said polymer is present in an amount between about 4 percent by weight of said viscoelastic gel. .Iaddend. .Iadd.14. The method of claim 7 wherein said polymer is polyacrylamide. .Iaddend. .Iadd.15. The method of claim 7 wherein said viscoelastic gel comprises
(a) 2 to 5 percent by weight of said polymer;
(b) 0.4 to 8.6 percent by weight sodium chloride;
(c) 0.075 to 0.3 percent by weight potassium chloride;
(d) 0.04 to 0.33 percent by weight calcium chloride;
(e) 0.02 to 0.04 percent by weight magnesium chloride hexahydrate;
(f) 0.3 to 0.4 percent by weight sodium acetate;
(g) 0.15 to 0.20 percent by weight buffering agent; and
(h) remainder water. .Iaddend. .Iadd.16. The method of claim 15, wherein said buffering agent is sodium citrate dihydrate. .Iaddend. .Iadd.17. The method of claim 7 wherein said viscoelastic gel consists essentially of about 4 percent by weight of said polymer having a molecular weight of about 5 million, about 0.49 percent by weight sodium chloride, about 0.075 percent by weight potassium chloride, about 0.048 percent by weight calcium, about 0.03 percent by weight magnesium chloride hexahydrate, about 0.17 percent by weight sodium citrate dihydrate, remainder water. .Iaddend.
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  0.4-8.6potassium chloride            0.075-0.3calcium chloride 0.04-0.33magnesium chloride            0.02-0.04hexahydratesodium acetate   0.3-0.4buffer           0.15-0.20water            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   4.0sodium chloride  0.049potassium chloride            0.075calcium chloride 0.048magnesium chloride            0.030hexahydratesodium acetate   0.390sodium citrate dihydrate            0.170water            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            4.0sodium chloride  0.049potassium chloride            0.075calcium chloride 0.048magnesium chloride            0.030hexahydratesodium acetate   0.390sodium citrate dihydrate            0.170water            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.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3868445 *Nov 16, 1973Feb 25, 1975Pharmacia AbDosage unit containing a substance showing a topical effect on the eye, and a method of preparing same
US3920810 *Apr 23, 1974Nov 18, 1975Burton Parsons And Company IncPolyacrylamide containing ophthalmic solutions
US3978201 *Nov 12, 1975Aug 31, 1976Gennady Lvovich KhromovBase for ophthalmological medicinal preparation on opthalmological medicinal film
US4003991 *Aug 27, 1974Jan 18, 1977National Patent Development CorporationWater soluble acrylic, 2-alkenamide, or ethylenimine polymer; topical medicaments
Non-Patent Citations
Reference
1 *Chem. Abst. 76:90019(j) (1972) Lemp et al.
2Chem. Abst. 76:90019(j) (1972)-Lemp et al.
3 *Chem. Abst., 76:90018(h) (1972) Leong et al.
4Chem. Abst., 76:90018(h) (1972)-Leong et al.
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US5505959 *Mar 31, 1994Apr 9, 1996Nestec S.A.Pharmaceutical composition in gel form in a dispensing package
US5629008 *Jun 7, 1994May 13, 1997C.R. Bard, Inc.Method and device for long-term delivery of drugs
US5631243 *Dec 28, 1994May 20, 1997Collagenesis Inc.Protective lubricants for eye surgery which can easily be removed, in mixture with mucopolysaccharides
US5639796 *Sep 7, 1993Jun 17, 1997C.R. Bard, Inc.Injectable medical composition and method of use
US5733562 *Jun 6, 1995Mar 31, 1998C.R. Bard, Inc.Injectable medical device and method of use
US5813411 *Aug 20, 1996Sep 29, 1998Menlo Care, Inc.Method of deforming tissue with a swollen hydrogel
US5855615 *Jun 7, 1996Jan 5, 1999Menlo Care, Inc.Controller expansion sphincter augmentation media
US6306418 *Jul 25, 1994Oct 23, 2001Robert Steven BleyInserting into tissue structure and into contact with body fluids physiologically acceptable formulation comprising plurality of physiologically acceptable relatively hard solid hydrophilic polymer particles dispersed in liquid carrier
US6423332May 26, 2000Jul 23, 2002Ethicon, Inc.Method and composition for deforming soft tissues
US6592859 *Aug 20, 1992Jul 15, 2003Ethicon, Inc.Controlled expansion sphincter augmentation media
US7049346Aug 20, 1996May 23, 2006Menlo Care Div Of Ethicon, Inc.Swollen hydrogel for sphincter augmentation
Classifications
U.S. Classification424/78.04, 514/912
International ClassificationA61L27/52, A61K9/00, A61L27/16, A61K31/785
Cooperative ClassificationA61L27/52, A61K9/0048, A61L2400/06, A61L27/16, A61K31/785
European ClassificationA61L27/16, A61K31/785, A61K9/00M16, A61L27/52
Legal Events
DateCodeEventDescription
Jul 8, 2003356Patent term extension under 35 u.s.c. 156
Free format text: PRODUCT NAME: ORCOLON
Expiry date: 20021014
Sep 7, 1999SULPSurcharge for late payment
Apr 15, 1997REMIMaintenance fee reminder mailed
Mar 10, 1993FPAYFee payment
Year of fee payment: 8