JPS62122671A - Production of high viscous liquid for intraocular operation - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] (Industrial application field) The present invention relates to a method for producing a highly viscous fluid for intraocular surgery.

(Prior art) As a highly viscous liquid for intraocular surgery, a solution prepared by dissolving sodium hyaluronate in a phosphate buffer is widely used, but its price is not necessarily cheap, and there are no substitutes with the same efficacy. It was wanted.

On the other hand, hydroxypropyl methyl cellulose (hereinafter referred to as "
A high viscosity liquid obtained by dissolving HPMC (abbreviated as "HPMC") is used as a high viscosity liquid for intraocular surgery.

(Problems to be Solved by the Invention) Through research by the present inventors, a highly viscous liquid for intraocular surgery in which HPMC and/or sodium hyaluronate are dissolved in a buffer containing glucose and bicarbonate ions has been developed. It was found to be extremely useful compared to known high viscosity liquids for the same purpose. However, when attempting to produce such a highly viscous liquid, the content of bicarbonate ions drops dramatically when dissolving HPMC and/or sodium hyaluronate, and in some cases, all of them decompose, resulting in the loss of the desired product. It was found that the concentration of bicarbonate ions in the liquid was insufficient.

(Means for Solving the Problems) As the buffer solution used in the present invention, a buffer solution having an aqueous humor-like composition prepared using various salts can be used. For example, halides of alkali metals or alkaline earth metals such as sodium, potassium, calcium,
Inorganic acid salts such as sulfates and nitrates, organic acid salts such as acetates, citrates, tartrates, etc. are appropriately mixed and used, and prepared to have a liquid quality and concentration similar to that of intraocular aqueous humor. is desirable. That is, the salt concentration is approximately 0.8 to 1.2 W/
■%, preferably about 0.9 to 1.1%, liquid property about 6 to
8. Preferably near neutrality. Specifically, a buffer solution obtained by dissolving sodium chloride, potassium chloride, magnesium sulfate, sodium citrate, sodium chloride, etc. to a total concentration of approximately IW/V% is used.

This buffer may contain sugars, if necessary. As the sugar, for example, glucose, xylitol, etc. are used, and the concentration thereof is preferably about 0.1 to 0.2 W/V%.

In the present invention, first, HPMC is added to the above buffer solution.
and/or the hyaluronate is dissolved.

HPMC and hyaluronate have a final product viscosity of 10
An amount of about 0.00 to 10,000 centivoids can be dissolved. Specifically, about 0.5 to 5.0 W/V
%, preferably 1.0 to 2.0 W/V%. When dispersing HPMC in a buffer solution, it is preferable to heat it appropriately.

The liquid temperature during dispersion is preferably around 70 to 90°C, and is usually carried out at about 75 to 85°C.

When dispersing, it is preferable to add and disperse HPMC in as small a quantity as possible with sufficient stirring.

In the present invention, an aqueous solution containing hydrogen carbonate ions is added to the HPMC solution. As the hydrogen carbonate ion source in the aqueous solution, it is preferable to use, for example, an alkali metal carbonate or hydrogen carbonate such as sodium hydrogen carbonate or potassium hydrogen carbonate.

The aqueous solution containing bicarbonate ions is preferably prepared by dissolving carbonate or bicarbonate in a small amount of water. The aqueous solution containing bicarbonate ions may contain other commonly used components as long as they do not contradict the purpose of the present invention.

When adding the aqueous solution containing bicarbonate ions to the buffer solution, it is best to do so while the temperature of the buffer solution is not high.

The liquid temperature during addition is preferably 20° C. or lower, at least room temperature or lower. It is desirable to add the mixture as gradually as possible, and then stir thoroughly to make it homogeneous. Next, an aqueous solution containing bicarbonate ions is added to adjust the properties of the resulting highly viscous liquid. To adjust the liquid,
While stirring the liquid, stir in the reagents normally used to adjust the liquid properties, such as hydrochloric acid and sodium hydroxide, until the pH reaches approximately 6.
It is preferable to add it until it is adjusted to about 8 to 8.

The highly viscous liquid thus obtained has a viscosity suitable for intraocular surgery, that is, a viscosity of around 1,000 to 10,000 centiboise, and can be effectively used during intraocular surgery by appropriately selecting the composition. can.

(Function) The highly viscous liquid for intraocular surgery obtained by the above method has bicarbonate ions in its components stably maintained at an effective concentration, and can be sealed in a container such as an ampoule or a vial. It can be stored for a long period of time and can be effectively used in intraocular surgery depending on the need.

(Example) Example 1 Sodium chloride 0.7 g, potassium chloride 0.04 g,
Magnesium sulfate 0.03g, glucose 0.15g.

Sodium acetate 0.06g, sodium citrate 0゜1
g and 0.02 g of calcium chloride in 75 m of sterile purified water.
1, and 2 g of HPMC was added little by little to this while stirring at a temperature of about 80° C., and the mixture was thoroughly dissolved. After cooling, add the solution obtained by dissolving 0.2 g of sodium hydrogen carbonate in 20 ml of sterile purified water to make a homogeneous liquid,
While stirring, add a small amount of 1N hydrochloric acid to adjust the pH to 7.4.
Further, sterile purified water was added to bring the total volume to 100 ml, and after pressure filtration, 5 ml each was dispensed and filled into ampoules and sterilized by heating to obtain a highly viscous liquid product for intraocular surgery.

Example 2 Sodium chloride 0.7g, potassium chloride 0.04g.

Magnesium sulfate 0.03g, glucose 0.15g1 sodium acetate 0.06g, sodium citrate 0°1g
and 0.02g of calcium chloride in 75ml of sterile purified water.
1 g of sodium hyaluronate was stirred and dissolved therein at room temperature. Next, a solution obtained by dissolving 0.2 g of sodium hydrogen carbonate in 20 ml of sterile purified water was added to the above to make a homogeneous liquid, and while stirring, a small amount of 1N hydrochloric acid was added to adjust the pH to 7.4. Further, sterilized purified water was added to make the total volume 100 ml, and after pressure filtration, 5 ml each was dispensed and filled into ampoules and sterilized by heating to obtain a highly viscous liquid product for intraocular surgery.

(Effects of the Invention) By the method of the present invention, bicarbonate ions can be stably added to a high viscosity liquid for intraocular surgery in which HPMC and/or hyaluronate are dissolved in an aqueous solution containing salts and/or sugars. It is possible to obtain a highly viscous liquid that is extremely effective in preventing corneal damage during intraocular surgery.

Claims (1)

[Claims] Hydroxypropyl methylcellulose and/or hyaluronate are dissolved in a buffer containing salts and/or sugars, and an aqueous solution of an alkali metal salt of carbonic acid or bicarbonate is added thereto, and the pH is adjusted to 6 to 8. A method for producing a highly viscous liquid for intraocular surgery, characterized by adjusting the liquid to