Intraocular device and method for preparing the same

Patent metadata

Field	Value
Publication number	US-2018193535-A1
Application number	US-201615741717-A
Country	US
Kind code	A1
Filing date	Jul 6, 2016
Priority date	Jul 6, 2015
Publication date	Jul 12, 2018
Grant date	—

Abstract

The present invention relates to an ocular device for regulating intraocular fluid pressure comprising or consisting of a tubular body wherein the inner surface of the tubular body or the inner and outer surface is/are coated with covalently immobilized hyaluronic acid (HA). In more specific embodiments, the tubular body comprises or consists of a biocompatible material selected from the group comprising a biocompatible metal such as titanium, ceramics, glass, polymers and composites thereof, and the immobilized hyaluronic acid molecules are linked with further HA molecules to form a HA hydrogel. The ocular device is a stent free from mechanical valves or other mechanical means for actively regulating the flow of intraocular fluid.

First claim

1 . An ocular device for regulating intraocular fluid pressure comprising a tubular body wherein an inner surface of the tubular body or the inner surface and an outer surface of the tubular body is/are at least partially coated with covalently immobilized hyaluronic acid (HA).

2 . The ocular device according to claim 1 , wherein the inner and outer surface of the tubular body are partially or completely coated with the covalently immobilized hyaluronic acid.

3 . The ocular device according to claim 1 , wherein the tubular body comprises a biocompatible material selected from the group consisting of a biocompatible metal, glass, polymers and composites thereof.

4 . The ocular device according to claim 1 , wherein the tubular body has a length in a range from 2.5 mm to 0.3 mm, and a diameter in a range from 2 mm to 100 μm, and a lumen with an inner diameter in a range from 1 mm to 50 μm.

5 . The ocular device according to claim 1 , wherein the tubular body and/or a lumen thereof has an annular cross-section.

6 . The ocular device according to claim 1 , wherein a surface of the tubular body is functionalized with reactive groups capable to react with functional groups of the hyaluronic acid such that the hyaluronic acid is immobilized via a covalent bond resulting from a covalent reaction between said reactive groups.

7 . The ocular device according to claim 6 , comprising a tubular body made of titanium wherein at least the inner surface of the tubular body has been silanized and thiol-modified hyaluronic acid molecules are immobilized onto at least the inner surface via a covalent bond which is a result of a coupling reaction between epoxide groups on a silanized titanium surface and hydroxyl- and/or thiol groups of the thiol-modified hyaluronic acid molecules.

8 . The ocular device according to claim 1 , wherein the immobilized hyaluronic acid molecules on at least the inner surface of the tubular body are linked with further HA molecules to form a HA hydrogel.

9 . The ocular device according to claim 8 , wherein the immobilized hyaluronic acid molecules are linked with the further HA molecules to form the HA hydrogel via crosslinkers with acrylic groups selected from the group consisting of polyethylene(glycol)-diacrylamide (PEG-DA), N,N′-methylenebisacrylamide (MBBA), N 3 ,N 5 -bis(2-acrylamidoethyl)pyridine-3,5-dicarboxamide, 3,5-((2-acrylamidoethyl)carbamoyl)-1-methylpyridin-1-ium iodide, piperazine diacrylamide, N,N′-(1,2-dihydroxyethylene)-bisacrylamide, and N,N-bis(acryloyl) cystamine.

10 . The ocular device according to claim 8 , wherein the immobilized hyaluronic acid molecules or the HA hydrogel is/are linked with additional cell adhesion-regulating molecules.

11 . The ocular device according to claim 9 , wherein the surface of the tubular body is free from cell adhesion-regulating molecules other than hyaluronic acid.

12 . The ocular device according to claim 1 , which is a stent free from mechanical valves or other mechanical means for actively regulating a flow of intraocular fluid through said device.

13 . The ocular device according to claim 1 , wherein a lumen of the tubular body is filled with a compressible crosslinked HA hydrogel which comprises a channel extending in a longitudinal direction of the tubular body, which channel is closed as long as an external liquid pressure applied to an end portion of the tubular body is below a specific threshold value, and which channel is open if said external liquid pressure is above said threshold value and compresses the HA hydrogel.

14 . The ocular device according to claim 13 , wherein structural properties of the crosslinked HA hydrogel are provided in predetermined ranges by adjusting one or more of parameters selected from the group consisting of HA concentration, thiolation degree of HA, type of crosslinker(s) and concentration of crosslinker(s).

15 . A method for preparing the ocular device according to claim 1 comprising at least the following steps:
a) providing the tubular body having predetermined dimensions;
b) introducing functional groups onto the inner surface or the outer and inner surface of the tubular body;
c) reacting the functional groups of the inner surface or of the inner and outer surface of the tubular body with reactive groups of hyaluronic acid resulting in covalently immobilized hyaluronic acid molecules; and
d) optionally crosslinking of the immobilized hyaluronic acid molecules with further HA molecules and suitable crosslinkers to form a HA hydrogel.

16 . The method according to claim 15 , wherein the tubular body provided in step a) is made of titanium, the functional groups introduced in step b) are epoxide groups introduced by silanization of the surface(s) of the tubular body, and the immobilization of hyaluronic acid in step c) occurs via a coupling reaction of the epoxide groups on the surface(s) and hydroxyl and/or thiol groups of thiol-modified hyaluronic acid.

17 . A method for preparing an ocular device according to claim 13 , comprising at least the following steps:
a) providing the tubular body having predetermined dimensions and providing an elongated removable element, in the lumen of the tubular body in a predetermined distance from the inner surfaces of the tubular body, and which element extends in the longitudinal direction of the lumen of the tubular body; b) introducing functional groups onto the inner surface or the outer and inner surface of the tubular body; c) reacting the functional groups of the inner surface or of the inner and outer surface of the tubular body with reactive groups of hyaluronic acid resulting in covalently immobilized hyaluronic acid molecules; d) crosslinking the immobilized hyaluronic acid molecules on at least the inner surface with further HA molecules and suitable crosslinkers to form a crosslinked HA hydrogel; and e) removing the elongated removable element after gel formation leaving a channel with dimensions corresponding to that of said elongated element in the crosslinked HA hydrogel.

18 . A method for preparing the ocular device according to claim 13 comprising at least the following steps:
a) providing the tubular body having predetermined dimensions;
b) introducing functional groups onto the inner surface or the outer and inner surface of the tubular body;
c) reacting the functional groups of the inner surface or of the inner and outer surface of the tubular body with reactive groups of hyaluronic acid resulting in covalently immobilized hyaluronic acid molecules;
d) crosslinking the immobilized hyaluronic acid molecules on at least the inner surface with further HA molecules and suitable crosslinkers to form a crosslinked HA hydrogel which fills the lumen of the tubular body; and
e) generating a channel in the crosslinked HA hydrogel which extends in the longitudinal direction of the tubular body by irradiating an open end portion of the crosslinked HA hydrogel obtained after step d) above in the lumen of the tubular body with a laser beam in the longitudinal direction of the tubular body and the crosslinked HA hydrogel with a sufficient energy and for a sufficient time period to obtain an end-to-end channel in said crosslinked HA hydrogel.

Assignees

• Max Planck Gesellschaft

Inventors

• Spatz Joachim P
• Geiger Fania
• Thaller Michael
• Lingenfelder Christian
• Boehm Heike

Classifications

• A61L31/022

  Metals or alloys · CPC title

• A61F2240/001

  Designing or manufacturing processes · CPC title

• A61L2430/16

  for reconstruction of eye parts, e.g. intraocular lens, cornea · CPC title

• A61L31/04

  Macromolecular materials · CPC title

• A61L31/10 Primary

  Macromolecular materials · CPC title