EP-4735063-A1 - KIT FOR USE IN EYE SURGERY, AND OPHTHALMIC VISCOELASTIC DEVICE

Abstract

The invention relates to a kit for use in eye surgery, said kit comprising: an ophthalmic viscoelastic device that has at least one viscoelastic polymer; and at least one cleaving agent by means of which the viscoelastic polymer can be cleaved into polymer chains with a lower molecular weight, wherein the viscoelastic polymer can be cleaved in vivo by means of the cleaving agent into polymer chains which have an average molecular weight of at most 4 MDa. The at least one viscoelastic polymer of the ophthalmic viscoelastic device comprises disulfide bridges, while the cleaving agent is designed to cleave at least a portion of said disulfide bridges. The invention also relates to an ophthalmic viscoelastic device comprising at least one viscoelastic polymer which has disulfide bridges and can be cleaved into polymer chains with a lower molecular weight by means of a cleaving agent, wherein the viscoelastic polymer can be cleaved in vivo by means of the cleaving agent into polymer chains which have an average molecular weight of at most 4 MDa.

Inventors

• ALBRECHT, CHRISTIAN
• ROBERTSON, BEN

Assignees

• Carl Zeiss Meditec AG
• HYALTECH LIMITED

Dates

Publication Date

20260506

Application Date

20240624

Claims (10)

1. 1. Kit for use in an eye operation, comprising an ophthalmic viscoelastic device comprising at least one viscoelastic polymer, and at least one cleaving agent by means of which the viscoelastic polymer can be cleaved into polymer chains with a lower molecular weight, characterized in that the at least one viscoelastic polymer of the ophthalmic viscoelastic device comprises disulfide bridges and that the cleaving agent is designed to cleave at least a portion of these disulfide bridges, wherein the viscoelastic polymer can be cleaved in vivo by means of the cleaving agent into polymer chains which have an average molecular weight of at most 4 MDa.
2. 2. Kit according to claim 1, characterized in that the viscoelastic polymer and the cleaving agent are coordinated with one another in such a way that the cleaving agent cleaves at least 70%, in particular at least 80%, of all disulfide bridges of the viscoelastic polymer in vivo within a maximum of 9 hours, in particular within a maximum of 6 hours, particularly preferably within a maximum of 4.5 hours, and/or the viscoelastic polymer can be cleaved by means of the cleaving agent in vivo into polymer chains which have an average molecular weight between 0.5 kDa and 3 MDa, particularly preferably between 0.1 kDa and 1 MDa, and/or the viscoelastic polymer can be cleaved by means of the cleaving agent in vivo into particles with an average particle size of a maximum of 600 nm, in particular an average particle size between 200 nm and 500 nm.
3. 3. Kit according to claim 1 or 2, characterized in that the splitting agent comprises a reducing agent which in particular comprises one or more thiol groups, preferably N-acetylcysteine, glutathione or a mixture thereof.
4. 4. An ophthalmic viscoelastic device comprising at least one viscoelastic polymer which is cleavable by means of a cleavage agent into polymer chains of lower molecular weight, characterized in that the at least one viscoelastic polymer comprises disulfide bridges, wherein the viscoelastic polymer is cleavable by means of the cleavage agent in vivo into polymer chains which have an average molecular weight of at most 4 MDa.
5. 5. Ophthalmic viscoelastic device according to claim 4, characterized in that the at least one viscoelastic polymer comprises at least one forming block from the group consisting of hyaluronic acid, alginate, chitosan, methylcellulose, hydroxypropylmethylcellulose, chondroitin sulfate, collagen and gelatin.
6. 6. Ophthalmic viscoelastic device according to claim 4 or 5, characterized in that the at least one viscoelastic polymer comprises polymer chains which are linked end-to-end via disulfide bridges.
7. 7. Ophthalmic viscoelastic device according to one of claims 4 to 6, characterized in that the at least one viscoelastic polymer comprises polymer chains which are cross-linked by means of at least one cross-linking agent, in particular from the group 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide, dithiodipropionic acid dihydrazide, glutathione and any mixtures thereof, and/or that the at least one viscoelastic polymer has a degree of cross-linking between 0.1% and 100%.
8. 8. Ophthalmic viscoelastic device according to one of claims 4 to 7, characterized in that This is designed as a dispersive ophthalmic viscoelastic device.
9. 9. Ophthalmic viscoelastic device according to one of claims 4 to 8, characterized in that a concentration of the at least one viscoelastic polymer based on the total volume of the ophthalmic viscoelastic device is between 0.1 mg/ml and 50 mg/ml.
10. 10. Ophthalmic viscoelastic device according to one of claims 4 to 9, characterized in that it comprises at least one therapeutic agent, in particular an analgesic and/or an antioxidant, wherein the therapeutic agent is preferably not covalently bound to the at least one viscoelastic polymer.

Description

Kit for use in eye surgery and ophthalmic viscoelastic device technical field The invention relates to a kit for use in eye surgery and a degradable ophthalmic viscoelastic device. State of the art Cataracts are a common condition, especially in the elderly, in which the lens of the eye gradually becomes opaque. This clouding of the natural lens leads to a loss of visual acuity. Cataract surgery is required to restore vision. The standard method of removing the cloudy lens nucleus to create a capsular bag for the insertion of an artificial intraocular lens (IOL) is called phacoemulsification, using a device that generates ultrasonic vibrations. Immediately before phacoemulsification, the anterior chamber is usually filled with a so-called ophthalmic viscoelastic device (OVD). The viscoelastic OVD is used as a surgical aid to protect the intraocular tissue (e.g. the corneal endothelium during phacoemulsification), as a space maintainer (e.g. to maintain the anterior chamber of the eye) and to facilitate intraocular interventions, such as performing a controlled capsulorhexis. However, such OVDs are also used in other eye operations, such as corneal transplants or glaucoma operations. OVDs are usually water-based solutions containing viscoelastic polymers such as hyaluronic acid (HA), chondroitin sulfate (CS), hydroxypropylmethylcellulose (HPMC) or mixtures thereof. The viscoelastic composition can vary by the molecular weight of the polysaccharide dissolved in the solution, by the concentration of the polysaccharide and by the viscosity of the solution. The rheological Properties depend strongly on the concentration and molecular mass of the polymers. In general, two types of OVDs are distinguished. Highly viscous, cohesive OVDs hold the space and build up pressure. They are used, for example, to dilate the pupil before the anterior capsular bag of the lens is opened (capsulorhexis). Cohesive OVDs are made of polymers with a high molecular weight. In contrast, less viscous, dispersive OVDs envelop and protect the tissue. One of the most important applications is the construction of an adherent polymer barrier with a layer thickness of about 100 pm to about 1 mm between the corneal endothelium of the anterior chamber of the eye. Disperse OVDs contain polymer chains with a lower molecular weight compared to cohesive OVDs. While a longer-chain, cohesive OVD can be easily washed out by flushing the anterior chamber with irrigation solution, shorter-chain, dispersive OVDs are much more difficult to remove or aspirate after surgery. At the end of cataract surgery, the surgeon is often faced with a layer of OVD covering the cornea and extending to the corner of the eye. An additional challenge is that the dispersive OVD material is usually located directly on the endothelium, where it is generally difficult to aspirate, and in the corner of the eye, where it is also difficult to detect. Residues of OVD that remain in the eye after surgery can be gradually washed out by the aqueous humor and transported away via the trabecular meshwork. However, polymer chains that are too long can partially block the trabecular meshwork and delay or completely prevent removal. This can then lead to increased intra ocular pressure (IOP) after surgery. What is needed is a biocompatible ophthalmic viscoelastic device that can be degraded after surgery to allow natural removal by water flow and drainage via the trabecular meshwork. US 6,745,776 B2 discloses an eye surgery procedure in which a kit consisting of an OVD with hyaluronic acid as a viscoelastic polymer and hyaluronidase as a breaking agent is used. During the surgical procedure, appropriate amounts of hyaluronidase are simultaneously added to the OVD in order to break down the hyaluronic acid over time and thus avoid a postoperative increase in intraocular pressure. A disadvantage of this well-known kit is the fact that it can lead to the uncontrolled dissolution of the body's own hyaluronic acid, which can lead to corresponding problems. representation of the invention The object of the present invention is to provide a kit for use in the context of eye surgery which reduces the risk of an increase in intraocular pressure after the eye surgery without having to accept problems caused by an uncontrolled dissolution of the body's own hyaluronic acid. A further object of the invention is to create a correspondingly advantageous ophthalmic viscoelastic device. The object is achieved according to the invention by a kit according to claim 1 for use in an eye operation and by an ophthalmic viscoelastic device according to claim 4. Advantageous embodiments with expedient embodiments of the invention are specified in the subclaims, wherein advantageous embodiments of each aspect of the invention are to be regarded as advantageous embodiments of the other aspect of the invention. A first aspect of the invention relates to a kit for use in an eye operation, comprising an ophthalmic