Ocular inserts

• US 5,660,851 A
• Filed: 06/05/1995
• Issued: 08/26/1997
• Est. Priority Date: 12/26/1989
• Status: Expired due to Fees

• Current Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Original Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Inventors: Domb, Abraham Jacob
• Primary Examiner(s): Sweet, Mark D.
• Application Number:
  US08/464,330
• Time in Patent Office: 813 Days
• Field of Search: 424/427, 424/428, 528/271
• US Class Current: 424/427
• CPC Class Codes: A01N 37/14 containing the group; Thio analogues thereof
• CPC Class Codes: A01N 37/20 containing the group , wherein Cn means a carbon skeleton not containing a ring; Thio analogues thereof
• CPC Class Codes: A01N 39/02 Aryloxy-carboxylic acids; Derivatives thereof
• CPC Class Codes: A01N 39/04 Aryloxy-acetic acids; Derivatives thereof
• CPC Class Codes: A01N 49/00 Biocides, pest repellants or attractants, or plant growth regulators, containing compounds containing the group , wherein m+n>=1, both X together may also mean —Y— or a direct carbon-to-carbon bond, and the carbon atoms marked with an asterisk are not part of any ring system other than that which may be formed by the atoms X, the carbon atoms in square brackets being part of any acyclic or cyclic structure, or the group , wherein A means a carbon atom or Y, n>=0, and not more than one of these carbon atoms being a member of the same ring system, e.g. juvenile insect hormones or mimics thereof containing hydrocarbons A01N27/00
• CPC Class Codes: A61F 2/16 Intraocular lenses
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 47/542 Carboxylic acids, e.g. a fatty acid or an amino acid
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants

Abstract

Absorbable ocular inserts fabricated of materials that are biologically inert, biodegradable, non-allergenic, and insoluble in tear liquid, and a method for delivering substances to the eye using the ocular insert, are disclosed. In embodiment A of the invention, the insert and method include the covalent attachment of a carboxylic acid-containing substance to be delivered to a polymer that contains pendent carboxylic acid groups, through anhydride linkages. The drug is released over time by hydrolysis of the anhydride bonds. In embodiment B of the invention, a substance to be delivered (whether or not it contains a carboxylic acid group) is dispersed within an anhydride polymer or copolymer matrix and the mixture is formed into an appropriately shaped article for ocular delivery. In embodiment C of the invention, the insert and method include the covalent attachment of a carboxylic acid-containing substance to be delivered to a polymer that contains pendent carboxylic acid groups through methylene diester bonds which degrade in vivo over time.

Claims

1. An ocular insert comprising a carboxylic acid-containing biologically active compound bound to a polyacid containing pendent carboxylic acid groups through an anhydride or methylene diester bond.

2. The insert of claim 1, wherein the polyacid is selected from the group consisting of polymers and copolymers of (meth)acrylic acid, maleic acid or vinylacetic acid.

3. The insert of claim 1, wherein the polyacid is an ester, partial ester, or anhydride of a polyacrylic acid with a compound containing more than one carboxylic acid.

4. The insert of claim 3 wherein the compound containing more than one carboxylic acid is citric acid.

5. The ocular insert of claim 1, wherein the biologically active compound is ofloxacin or ibuprofen.

6. The ocular insert of claim 1, wherein the polyacid is selected from the group consisting of a polymer or copolymer of (meth)acrylic acid or (meth)acrylate.

7. The ocular insert of claim 4, wherein the polyacid is a copolymer of (meth)acrylic acid with (meth)acrylate.

8. The ocular insert of claim 1, wherein between 10 and 60 percent of carboxylic acid groups are bound to the biologically active compound.

9. The ocular insert of claim 1, wherein fatty acid residues are bound to the polyacid.

10. The ocular insert of claim 1, further comprising other polymers or additives.

11. The ocular insert of claim 10, wherein the polymers are selected from the group consisting of polyglycolic acid, collagen, polyorthoesters, polylactic acid, cellulose ester derivatives, dextran and its derivatives, albumin, gelatin, hyaluronic acid, amylose and its derivatives, poly(vinyl alcohol), maleic anhydride derivatives, and polyphosphazenes.

12. The ocular insert of claim 1 in the form of a film.

13. The ocular insert of claim 1 wherein the thickness of the device is between approximately 0.01 and 2 mm.

14. The ocular insert of claim 1, wherein the width of the insert is between approximately 5 and 100 mm².

15. The ocular insert of claim 1 wherein the carboxylic acid-containing compound is covalently bound to the polyacid using a methylene diester bond.

16. The ocular insert of claim 1 further comprising a plasticizer.

17. The ocular insert of claim 16, wherein the plasticizer is selected from the group consisting of acetyl tri-n-butyl citrate, polyethylene glycol (600), epoxidized soybean oil, glycerol monoacetate, polyethylene glycol, propylene glycol dilaurate, decanol, dodecanol, 2-ethyl hexanol, 2,2-butoxyethanol ethylene glycol and tributyl citrate.

18. A method for the delivery of a biologically active substance comprising administering the substance in the ocular insert of claim 1.