Process for preparing objects made of biocompatible hydrogel for uses thereof in the medical field, and more particularly in ophthalmology

Abstract

The present invention relates to a process for manufacturing an object made of biocompatible hydrogel by molding a polymer solution in a mold made of a particular material, said process comprising the following steps: (i) preparation of a polymer solution by dissolving a copolymer of acrylonitrile and of an olefinically unsaturated co-monomer bearing anionic groups in an aprotic solvent, optionally in the presence of a nonsolvent, (ii) shaping and the start of gelation of the polymer solution obtained at the end of step (i) in a mold consisting of a material containing said nonsolvent or of a material permeable to said nonsolvent, (iii) immersion of the object undergoing gelation resulting from step (ii) in a nonsolvent. The present invention also relates to the objects made of biocompatible hydrogel resulting from this process such as, for example, intracorneal lenses (or lenticules) implantable in the cornea or any other implants usable in ophthalmology.

Claims

1. A process for manufacturing an object made of biocompatible hydrogel, characterized in that it comprises the following steps: (i) preparation of a polymer solution by dissolving a copolymer of acrylonitrile and of an olefinically unsaturated co-monomer bearing anionic groups in an aprotic solvent, optionally in the presence of a nonsolvent, (ii) shaping and the start of gelation of the polymer solution obtained at the end of step (i) in a mold made of hydrogel, (iii) immersion of the object undergoing gelation resulting from step (ii) in a nonsolvent.

2. The process as claimed in claim 1, wherein the acrylonitrile/co-monomer copolymer has a molar ratio in the range from 90/10 to 100/0.

3. The process as claimed in claim 1, wherein the anionic groups of the olefinically unsaturated co-monomer are selected from the sulfonate, carboxylate, phosphate, phosphonate and sulfate groups.

4. The process as claimed in claim 1, wherein the acrylonitrile/co-monomer copolymer is an acrylonitrile-sodium methallylsulfonate copolymer.

5. The process as claimed in claim 1, wherein the aprotic solvent is selected from the organic or inorganic polar aprotic solvents.

6. The process as claimed in claim 5, wherein the aprotic solvent is selected from dimethylformamide (DMF), dimethylsulfoxide (DMSO), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP).

7. The process as claimed in claim 1, wherein the nonsolvent is selected from water, aqueous solutions of mineral salt and aqueous solutions of organic salt.

8. The process as claimed in claim 7, wherein the nonsolvent is selected from water or an aqueous solution of sodium chloride.

9. The process as claimed in claim 1, wherein the mold in step (ii) is a mold made of hydrogel based on agarose, alginates, polyhydroxyethyl methacrylate (PHEMA), polyhydroxypropyl methacrylate (PHPMA) or polyacrylate.

10. The process as claimed in claim 9, wherein the mold in step (ii) is a mold made of agarose hydrogel.

11. The process as claimed in claim 9, wherein the mold in step (ii) consists of: from 1 to 10 wt %, of agarose or of alginates, and from 90 to 99 wt %, of water or of an aqueous solution of mineral salt or of an aqueous solution of organic salt.

12. The process as claimed in claim 1, wherein the immersion step (iii) is carried out in two steps: firstly: immersion of the object undergoing gelation in a cold bath of nonsolvent, preferably at a temperature in the range from 0 to 10 C., and secondly: immersion of the object undergoing gelation in a bath of nonsolvent, at room temperature.

13. The process as claimed in claim 2, wherein the acrylonitrile/co-monomer copolymer has a molar ratio in the range from 95/5 to 99/1.

14. The process as claimed in claim 11, wherein the amount of agarose or of alginates is from 2 to 6 wt %.

15. The process as claimed in claim 11, wherein the amount of water or of an aqueous solution of mineral salt or of an aqueous solution of organic salt is from 94 to 98 wt %.

Description

EXAMPLE

Manufacture of a Contact Lens in Hydrogel of AN-69 Copolymer According to the Process of the Invention

(1) Preparation of a Mold Made of Agarose Hydrogel:

(2) The agarose hydrogel mold is prepared from a polypropylene matrix (male part and female part) of a contact lens, supplied by the company Essilor.

(3) An aqueous solution of agarose at 2-4% is prepared by dissolving agarose in isotonic solution (at 0.9% of NaCl in H.sub.2O) at a temperature of 80 C. It is then cooled to a temperature of 40-50 C., and poured into the polypropylene matrix (into the two parts separately).

(4) After cooling to room temperature, the two parts of the agarose mold obtained are removed from the mold. The two parts of the mold are then immersed in physiological solution (at 0.9% of NaCl in H.sub.2O).

(5) Preparation of a Polymer Solution:

(6) A polymer solution corresponding to the composition shown below is prepared, with stirring, and on a water bath at a temperature of 60 C.:

(7) TABLE-US-00001 Constituents wt % AN-69 copolymer (dry extract) 9 Dimethylformamide (DMF) 85 Physiological solution 6 (at 0.9% of NaCl in H.sub.2O)

(8) Manufacture of a Contact Lens:

(9) A drop of the previously prepared polymer solution is poured into the previously prepared female part of the agarose hydrogel mold. The female part of the mold is closed immediately with the male part.

(10) After 30 seconds, the mold is opened. Extraction of the gelled form of the contact lens is then undertaken. It is immersed twice in succession for 30 minutes in 0.5 L of physiological solution at room temperature, which leads to complete exchange of the DMF (solvent) with the physiological solution (nonsolvent).

(11) A contact lens is thus obtained with a diameter of 10 mm having a thickness at the center of 0.3-0.4 mm. It has an optical power of 2.5 D and an average water capacity (water content) of 75%.

(12) The contact lens is then sterilized with gamma rays. The gamma radiation dose absorbed is 25 Gray (or 2.5 MRad).

(13) After sterilization, the contact lens is placed in a capsule containing physiological saline.

(14) The following observations are made: the shape of the lens (convex/concave) has not been altered, the water capacity has decreased by 2%, the optical power has changed very slightly (0.25 D).