HU205961B - Process for producing methyl-silicon-oil for replacing subretinal liquide and/or vitreous body with eye operations - Google Patents

Abstract

Oils with viscosity of 0.20, 0.50 and 1 m3/s are mixed in the ratio-by-mass of 1:1:1, to prepare ethalon. A chromatogram is produced using a high performance chromatograph, and the area under the curve (TE) is determined. Then 200 parts-by-mass of quasi-cosmetic-quality methyl-silicone-oil is added to 600 part-by-mass of a mixture made up of 80-98% ethalon, 1-10% glycerine and 1-10% water. The mixture is intensively mixed, then after allowing 1/2 hour for settlement, the oil phase is freed of solvents (its solvent content is reduced to below 0.01%) by centrifugation at 2000 rpm. minimum speed, and drying. - A chromatogram of the product is taken, and the area (TK) under the curve (representing the small mol-mass oligomer components) is determined. The area obtained satisfies the relationship. TK=TE/10

Description

The present invention relates to a process for the preparation of methyl silicone oil for use in ophthalmic surgery. In the process of the present invention, methyl silicone silicone oil of cosmetic purity is extracted with a ternary solvent mixture of ethanol, glycerol and water, and the oil is separated and de-solvented.

Eye surgery to remove the subretinal fluid and / or vitreous humor has long been known. Filling them is necessary for functional reasons. Methyl silicone oil has also been used (Moleau PG, Trans Ophtalmol. Soc. UK 84 164 1964). However, after a few weeks of smooth eye operation, fluid cloudiness was observed. Subsequently, by examining the physico-chemical properties of the methyl silicone oil, it was found that the filling quality is favorably influenced by the viscosity of the methyl silicone oil. Most preferred is a methyl silicone oil having a viscosity value of 1000-5000 mm ² s ^-! . (Scott I. D. Trans Ophtalmol. Soc. UK 92 351 1972). Using the above-mentioned viscosity methyl silicone oil, filling during eye surgery provides a smooth operation for one to two months, after which this fluid must be replaced.

In our studies, by examining the turbidity process, we found that it was caused by the formation of emulsions and the formation of finely divided emulsified droplets. Analyzing the emulsified droplets, it was surprisingly recognized that they consist of cyclosiloxanes and other low molecular weight methyl siloxane oligomers.

From this, it has become apparent to us that methyl silicone oil which can be used effectively in eye surgery can be prepared by removing low molecular weight molecules and oligomers from the methyl silicone oil. Suitable silicone oils for various purposes are prepared by appropriately selecting and adjusting the degree of polymerization. These procedures are summarized in Noll. W., Chemie und Technologie dér Silicone. Verlag Chemie GmbH. Veinheim 1968 monograph. However, no method for selectively removing individual components of methyl silicone oil has become known. The difficulty of the problem lies in the fact that the solvents commonly used in the plausible extraction methods are inappropriate in this case, since the methyl siloxanes are solubilized regardless of their molecular weight, and very few solvents which can be used as solvents are required. cause adverse effects on the eyes.

In a large number of experiments, the unexpected result was that a mixture of ethanol, glycerol, and water in the temer mixture met both conditions. That is, it selectively dissolves the low molecular weight oligomers from the methyl silicone oil and is also harmless to the body. Our results are also surprising because ethyl alcohol alone does not exhibit selectivity in molecular weight when dissolving methyl siloxane.

The process for producing methyl silicone oil suitable for filling in ophthalmic surgery according to the invention is based on cosmetic grade methyl silicone oil. The process consisted of extracting the methyl silicone oil with a mixture of at least three volumes of 80-98% ethanol, 1-101% glycerol and 1-101% water with stirring for at least 30 minutes, and after settling the oil phase was separated by centrifugation. , then removed by drying.

The low molecular weight oligomer content of the methyl silicone oil obtained by the process (a fraction having a viscosity of 100 nmr1 or less) is reduced to ^one hundred percent or less of the cosmetic grade methyl silicone oil. ;

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l. example

A stirred vessel was charged with 20 l of methyl silicone oil of cosmetic purity. 60 L of 96% ethanol, 2% glycerol and 2% water were added with stirring. The 20 ° C mixture was extracted at 200 rpm for 40 minutes.

After a further 30 minutes of rest, the oily phase was separated. The residual solvent was removed from the oily phase by centrifugation at 2000 rpm. The resulting oil was dried under an infrared lamp for 35 minutes. The product obtained was subjected to chromatography.

Chromatographic conditions:

80/120 Carbopack B AW 15% 20 H 2mxl / 4 0Dx2 mm ID glass column Temperature 80 ° C

Carrier gas: NO

Speed 20 ml / min (for GC) or Waters 6000 S dispenser

250x8mm Zovbox QDS, 10m

Waters 510 Ri detector (for HPLC A)

Examined by GC, the sample was found to contain less than 0.01% solvent residue.

When analyzed by HPLC (used oligomeric mixture as a standard 20,100 MMV viscosity methyl siloxane), it was found that the volume fraction of below 100 mnrs ^-1 viscosity from baseline cosmetic grade (ICI) methyl silicone oil similar fraction of decreased part of the century. (Originally reduced by 1.5% to 0.014%.)

More than one hundred surgeries have been performed at the SOTE Ophthalmic Clinic and the POTE Ophthalmic Clinic using the methyl silicone oil produced by the process of the present invention. Based on the results, it was found that no turbidity was observed after two years of filling with the methyl silicone oil obtained by the process of the invention, so that the fluid used to replace the subretinal and vitreous bodies did not need to be replaced.

Claims (1)

Patent Claim Point A process for the preparation of a methyl silicone oil for cosmetic grade silicone oil for the replacement of a subretinal fluid and / or vitreous in ophthalmic surgery, characterized in that the methyl silicone oil for cosmetic purity comprises at least three volumes of ol EN 205 961 B - wherein the solvent mixture is extracted with 80-98% ethanol, 1-10% glycerol and 1-101% water with stirring for at least 30 minutes, the oily phase is separated after settling for at least 30 minutes, the remaining solids are separated centrifugation, preferably 2000 rpm, followed by drying, preferably by infrared lamp,.