JPS615018A - Stable eye drop - Google Patents

Abstract

PURPOSE:To obtain a stable eye drop capable of preventing the clouding or formation of precipitates better than the conventional products, by incorporating a water-soluble high polymer in an eye drop containing flavin adenine dinucleotide (FAD) as a main a agent and a p-hydroxybenzoic acid ester as a preservative. CONSTITUTION:A stable eye drop obtained by incorporating a water-soluble high polymer, e.g. hydroxypropyl cellulose, hydroxyethyl cellulose or polyvinylpyrrolidone (PVP) in an eye drop containing flavin adenine dinucleotide (FAD) and a p-hydroxybenzoic acid ester. Hydroxypropyl cellulose having 2-4.2 number of added moles (MS) is used as the hydroxypropyl cellulose, and hydroxyethyl cellulose having 1.5-3MS is used as the hydroxyethyl cellulose. PVP having 10,000-700,000 average molecular weight is used as the PVP. The amount thereof to be used is preferably 0.1-0.5wt%. The formation of precipitates with time by irradiation with light can be more effectively prevented than the compounded glycyrrhizate product.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to flavin adenine dinucleotide (hereinafter referred to as
The present invention relates to a stable ophthalmic solution containing FAD) and paraoxybenzoic acid esters.

[Conventional technology]

Eye drops containing FAD and paraoxybenzoic acid esters cause precipitation over time when exposed to light. It is known that this precipitation formation over time can be prevented by incorporating glycyrrhizic acid or its salt (Japanese Patent Publication No. 55-18
689).

However, this method of blending glycyrrhizic acid etc. only delays the time when precipitate is formed, and also
At pH 5.5, where the stability of AD is said to be the highest, there are many problems such as precipitation formation due to light is faster than when glycyrrhizic acid or the like is not added.

[Problems to be Solved by the Invention] The present invention solves the problem of precipitation over time due to light irradiation in eye drops containing FAD and paraoxybenzoic acid esters, which could not necessarily be sufficiently prevented by adding glycyrrhizic acid or the like. The aim is to prevent the generation of

[Means for solving problems]

The present inventors have conducted extensive research into preventing precipitation of ophthalmic solutions containing FAD and paraoxybenzoic acid esters, which have the drawbacks described above. The present invention was completed based on the discovery that it is possible to prevent the formation of white turbidity or to extend the period until precipitation occurs.

That is, the present invention relates to a stable ophthalmic solution containing FAD and paraoxybenzoic acid esters, which is characterized in that it contains a water-soluble polymer compound.

Here, as the water-soluble polymer compound, cellulose derivatives such as hydroxypropylcellulose and hydroxyethylcellulose, or polyvinylpyrrolidone can be used. All of these are commercially available, and hydroxypropyl cellulose and hydroxyethyl cellulose have various physicochemical properties depending on the degree of polymerization and the number of added moles (MS) of hydroxyalkoxyl groups, but hydroxypropyl cellulose has MS of 2.0 to For hydroxyethyl cellulose, use MSI of 4.2 and MSI of 5 to 3.0. Polyvinyl vinylite lydone has an average molecular weight of 1 to 7.
Use 00,000. The amount used varies depending on the concentration of components that cause precipitation or cloudiness, but is generally 0.0
1 to 2% by weight, preferably 0.1 to 0.5% by weight.

[For production]

Control sample, sample 1 (glycyrrhizin #salt combination) sample (
Water-soluble polymer compound formulations) were prepared according to the following compositions, and a stability test was conducted using a white ampoule containing 10 sapons as a storage container.

Control sample F A D O, 02% Methyl paraoxybenzoate 0.03% Propyl paraoxybenzoate 0.01% Bofi6
1.6% borax
0-01% distilled water Total 100% sample I F A D O, 02% Methyl paraoxybenzoate 0.03% Propyl paraoxybenzoate 0.01% Boric acid
1.6% borax
0.01% dipotassium glycyrrhizin 0.
1% distilled water All 100% specimen ■ F A D O, 02% Methyl paraoxybenzoate 0.03% Propyl paraoxybenzoate 0.01% Boric acid
1.6% borax
0.01% water-soluble polymer compound 0.3-1
．． 0% runny nose All 100% experimental conditions are as follows.

(A) 25°C 5,000 Lux 24-hour irradiation (Cannon + Mercury lamp) (B) 25° 5,000 Lux 48-hour irradiation (Xenon + Mercury lamp) (C) Indoor scattered light The results of the 2-month stability test are shown in Table 1 below. As shown. Incidentally, the judgment was made by observing with the naked eye, and a case where a precipitate was formed was judged as +, and a case where a transparent solution was judged - as -.

Table 1 (+: Precipitate formation - 2. Transparent solution) As described above, the eye drops of the present invention do not form precipitates under any conditions, and hardly any cloudiness is observed, and is very stable.

〔Example〕

Examples of the present invention will be described in more detail below, but the present invention is not limited to these Examples.

Example 1 0.3 g paraoxybenzo-methyl and 0.3 g paraoxybenzo-propyl. Dissolve IJl in approximately 0.8Q of purified water by heating, and after cooling, add 0.2g of FAD.

15g of boric acid, 0.1s of borax and 3J of hydroxypropyl cellulose! , and the total amount is filtered aseptically as IQ.

Example 2 0.26 g of methyl paraoxybenzoate and 0.14 g of propyl paraoxybenzoate were heated and dissolved in about 0.8 Q of purified water, and after cooling, 25 g of F A D O and 16 s of boric acid were added.
Add 0.1 s of borax and 3 g of hydroxyethyl cellulose, and filter the entire amount as IQ aseptically.

Example 3 0.13 g of methyl paraoxybenzoate and 0.07 g of paraoxybenzo-propyl were heated and dissolved in about 0.8 Q of purified water, and after cooling, FAD (11 g of borax 8161, 0.0 g of borax) was dissolved.
Add 1s and 3g of polyvinyl pyrrolidone, and transfer the total amount to I.
Manufactured by sterile filtration using Q.

〔Effect of the invention〕

As described above, according to the stable eye drops of the present invention, FA
D is the main ingredient, paraoxybenzoic acid esters are the preservative,
Since the eye drops used as antibacterial agents contain a water-soluble polymer compound, they can be observed immediately after manufacture or over time. It is possible to prevent cloudiness and the formation of precipitates, and its effects are superior to those of conventional methods, making it extremely useful.

Patent applicant Zeria Pharmaceutical Industries Co., Ltd.

Claims (1)

[Scope of Claims] 1) A stable eye drop containing a flavin adenine dinucleotide and paraoxybenzoic acid ester, which is characterized in that it contains a water-soluble polymer compound. 2) The stable eye drop according to claim 1, wherein the water-soluble polymer compound is hydroxypropylcellulose, hydroxyethylcellulose, or polyvinylpyrrolidone.