JPH03135518A - Formulation for preparing preserving liquid for soft contact lens - Google Patents

Abstract

PURPOSE:To obtain the formulation which seals the harmful components contained in city water, more particularly, metallic change, and allows the use of the city water as a soft contact lens (SCL) preserving liquid as it is by incorporating a metal sealing agent, an isotonizing agent and a pH buffer agent into the prepn. CONSTITUTION:The metals which are the cause for the contamination of the SCL need be sealed in order to use the city water as a liquid for dissolving the preparing agent for the SCL preserving liquid and such sealing is attained by the metal sealing agent. The representative examples of the metal sealing agent which can be used include salts of ethylenediaminetetraacetic acid, nitrilotriacetate, diethylenetriamine penta acetic acid, citrate, condensed phosphate, and trans-2, 2- cyclohexadiaminetetraacetic acid. These metal sealing agents are harmless to the SCL and eyes and are, therefore, particularly preferable. These metal sealing agents vary largely in the needed amt. with the quality of the city water and are compounded with the prepn. at the ratio at which the metal sealing effect is sufficiently exhibited. The city water treated by the prepn. for preparing the SCL preserving liquid in such a manner is adequate for prepn. of the preserving liquid of the SCL.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a preparation for preparing a storage solution for soft contact lenses, and more particularly to a preparation for preparing a storage solution for soft contact lenses containing a sequestering agent.

[Prior Art] Soft contact lenses (hereinafter referred to as SCL) are contact lenses made of a flexible polymeric material containing water, and while they are more comfortable to wear than hard contact lenses, they are difficult to wear regularly. The drawback is that it takes time and money to store, clean, and disinfect the SCL in order to keep the lens in the best condition. In particular, since SCL removed from the eye must be preserved by immersing it in a preservation solution, physiological saline or an aqueous solution having similar properties is usually used as the SCL preservation solution. That is, commercially available physiological saline can be used as it is as an SCL preservation solution, or a commercially available preparation for preservation solution preparation (tablets or granules) containing sodium chloride as a main ingredient can be dissolved in commercially available purified water to prepare a preservation solution. Prepare
However, in this case, purified water without impurities must be used to dissolve the storage solution preparation, which is inconvenient for SCL users and also imposes a large economic burden. Met. Therefore, there has been a strong desire for a preparation for preparing an SCL storage solution that does not require the use of purified water and can use tap water or similar drinking water (hereinafter simply referred to as tap water) as a dissolving solution.

The main reason why tap water cannot be used as a 5CLI solution is that the various metals contained in tap water, such as calcium, magnesium, and iron, as well as the chlorine added to disinfect the water, have an adverse effect on the materials of eyes and lenses. This is because it is known to cause a blue color on the lens and stains on the lens surface. If the effects of these harmful components on the eyes and lenses contained in tap water could be removed, tap water could be used to prepare a preservation solution for SCL.

Furthermore, use tap water instead of purified water to make the preservation solution II.
Another advantage of using tap water is that it is almost sterile, so if you prepare it with it, you will have a large amount of clean, sterile stock solution.

[Problems to be Solved by the Invention] The present invention provides a formulation that sequesters harmful components, particularly metal components, contained in tap water and allows tap water to be used as is as an SCL preservation solution.

[Means for Solving the Problems] According to the present invention, the above problems are solved by a preparation for preparing a soft contact lens storage solution, which is characterized by containing a sequestering agent, an isotonizing agent, and a pH buffering agent. Ru.

According to the tap water quality standards (revised on August 31, 1973), the content of various metal ions is determined as follows.

Cu: 1.0mg#! Below F e: 0.
3mg/Q or less Mn: O'a'' Zn:
1.0 1lPb:0. l” Hexavalent C
r: 0.05 //Cd: 0.01”
As: 0.05 〃F: 0.8”
Ca, Mg, etc.: 300'/(as CaCO2) Organic phosphorus, mercury, and cyanide are not detected.

Hardness components such as calcium and magnesium, which cause SCL contamination, account for the majority of metal components in tap water, but their abundance in city water supplies is usually below the regulatory value of 115%.
~1/]O. Besides the metal components of carunium and magnesium, iron is the main cause of SCL stains. Since the source of contamination is mainly iron water pipes, which are hardly used in modern construction, the amount varies depending on the age of the pipes. do not have.

In order to use tap water as a solution for SCL preservation solution preparation, it is necessary to sequester these metals that cause SCL staining, and the present invention achieves this using a metal sequestering agent. .

Representative examples of sequestering agents that can be used in the formulation of the present invention include the following.

Ethylenediaminetetraacetate (hereinafter referred to as EDTA), such as EDTA.2Na, EDTA.3Na.

EDTA・4Na.

Nitrilotriacetate (hereinafter referred to as NTΔ), such as NTA
・2Na, NTA ・3Na.

Diethylenetriaminepentaacetate (hereinafter referred to as DPTA)
, e.g. DPTA・2NaSDPTΔ・3Na, DP
TA・4Na, DPTA・5Na.

Citrates, such as sodium citrate, ammonium citrate, condensed phosphates, such as sodium hexametaphosphate, shiichigo sodium phosphate, triple sodium phosphate trans-2,2-chlorohexanediaminetetraacetate (
(hereinafter referred to as CyDTA), for example, CyDTA.2Na.

These sequestering agents are particularly preferred as they are harmless to SCL and the eye. The required amount of these metal sequestering agents varies greatly depending on the quality of tap water, but it is necessary to mix the amount in such a way that the metal sequestering effect is sufficiently exerted. Assuming that the quality of tap water fluctuates from around 1/10 of the standard value to the upper limit, the amount of sequestering agents in the solution is 0 for EDTA and NTA, which represent complexanes.
．． The amount may be blended in the range of 0.01% to 1%, 0.01% to 1% for citrate, and o,oooi% to 1% for condensed phosphate. More preferably 0.02% to 0 for EDTA.
, 4%, NTAs 0.01% to 0.3%, citrates 0.02% to 0.3%, condensed phosphates 0.0
It may be set to 1% to 0.5%. It is well known that sodium hexametaphosphate, which represents a condensed phosphate, can inhibit the precipitation of Cal/Rum salt in small amounts, and when used in combination with other sequestrants, sodium hexametaphosphate can Even if calcium ions exist in an amount exceeding the metal sequestration capacity, precipitation of calcium salt crystals on the SCI can be prevented.

As the tonicity agent, inorganic salts such as sodium chloride and potassium chloride can be used, but sodium chloride is particularly preferred. There are no particular restrictions on the pH buffer, but in view of microbial contamination, a boric acid buffer system capable of antibacterial action is desirable.

The main rule is that this preparation is a storage solution preparation for SCL, so when this preparation is dissolved in tap water, the pH should be in the range of 6.0 to 7°4 and the osmotic pressure ratio should be in the range of 0.9 to 1.2. is desirable. When this preparation is dissolved in tap water, it is desirable that the preparation has the following composition in order to have the necessary amounts of each of the above components present.

Isotonic agent + 10-85 wt%, preferably 26-85 vt% Sequestering agent; 0,5-50 vt% preferably 14-35 wt% p) I buffering agent: up to 70 wL%, preferably up to 42 vt% Others: O~ 10wL% "Others" refers to components added for formulation, such as lubricants during tabletting.

There are no particular restrictions on the dosage form of this preparation, including regular powder, granules,
It can be made into tablets.

An example of how this preparation is actually used is shown below. When using the preparation according to the present invention, follow the basic rules: Completely dissolve one package in the case of powder or granules, or one tablet in the case of tablets in the specified amount of tap water, and then use the dissolved solution as a rinse agent for SCL. , used as a preservation solution or a preservation solution for boiling and disinfection. The effects, formulation examples, etc. of this preparation will be explained in more detail in the following examples.

Example 1 Preparation of iron standard solution First, accurately weigh 86.3 mg of ferric ammonium sulfate, dissolve it in 80 l (!) of water, add 0.5 m (l) of dilute hydrochloric acid, shake well, and then add water to make a total of 11,100 Jlc. Prepare an iron standard stock solution as follows. This stock solution contains 0.1ff9 of iron ions per Id. Pipette exactly 1 or 31 ml of this stock solution, put it in a 100Rρ volumetric flask, add water to make exactly 1100a+ (1) to prepare an iron standard solution (ippm or 3 ppm).

Preparation of EDTA solution (1.0%) Accurately weigh EDTA ・2Na (special grade reagent) f, Ov, put it in a 10ORQ volumetric flask, and add water to make exactly 100 cells.

Preparation of ammonium thiocyanate solution Dissolve ammonium thiocyanate (reagent grade) 1 Og in water at 100x.

Test time: Pour 10 samples of each of the following four test solutions 1 to ■ into a test tube with a stopper, and add 30 ml of ammonium persulfate (reagent special grade) to this.
R9 and ammonium thiocyanate solution 2x+! Add. For these test solutions, 550xm on a spectrophotometer
The absorption at a wavelength of ~400 nm is measured to obtain an absorption curve.

Test solution ■: Purified water test solution ■: Iron standard solution (iron concentration + 1 ppm) test solution ■゛:
Iron standard solution (iron concentration: 3 ppm) test solution III: ED
TAo, a liquid test solution prepared to contain 1 ppm of iron in a 2% aqueous solution [11': EDTAo, 3 ppm of iron in a 2% aqueous solution]
A test solution prepared to contain m, ? trfl' ha, EDTAi&(
1,0%) 20RI2 and iron standard stock solution 1RI2 or 3rtrQ respectively with a pipette, 100R
Q Put the volume into a volumetric flask, add water, and make sure the entire volume is Loo.
m(! Prepared by closing.

When iron ions and thiocyanine ions form a complex, they exhibit a red color, but when EDTA is present, the bond between EDTA and iron ions is stronger than the bond between iron ions and thiocyanine ions, so the color does not develop red. Test solutions ■ and ■゛ exhibited a red color, but test solutions ■ and ■° remained colorless like test solution I, indicating that the iron ions were sequestered by EDTA and did not combine with thiocyanine ions.

The absorption curves are shown in FIGS. 1 and 2.

As shown in these absorption curves, test solution J and
Then, due to the complex formation of thiocyanine ion and iron ion, 48
Although the spectrum was changed to have maximum absorption near 0 nm,
No such absorption was observed in test solutions (■) and (■'). This indicates that in the case of test solutions "■" and "■", the iron ions and EDTA were strongly bound together and could not react with other substances, and the iron ions were inactivated (sequestered). There is.

The above results show that tap water treated with the preparation for SCL preservation solution preparation of the present invention is suitable for the preparation of SCL preservation solution.

A prescription example is shown below.

Prescription (amount of each component contained in solution 10011Q) (Dissolution solutions with the above prescription codes a to f are neutral and exhibit an osmotic pressure ratio of approximately 1.) Example 2 Dissolution solutions with the formulations described in the prescription examples were prepared. were prepared to see if iron and calcium ions were actually sequestered.

1) Sequestration of iron ions When iron ions and thiocyanine ions form a complex, it appears red.

However, when EDTA is present, the bond between EDTA and iron ions is stronger than the bond between iron ions and thiocyanine ions, so iron ions and thiocyanine ions cannot form a complex and do not develop a red color. Therefore, using this property, we observed whether iron ions were sequestered by this preparation.

In the above prescription examples, solutions with prescription codes a, d, and f were prepared,
I checked to see if Chichi Aeon was actually blocked.

Place the following five test solutions I to ■ into 1oIQ test tubes with stoppers, and add ammonium persulfate 30R9 and ammonium thiocyanate solution (10%) 2+f! Add.

For these test solutions, 550 to 400 r with a spectrophotometer.
Absorption at a wavelength of +m was measured.

Test solution I: Purified water test solution ■: Iron standard solution (iron concentration: 1 ppm) Test solution ■ ° Double wrought iron standard solution Iron concentration + 3 ppm) Test solution ■: Prescription code a solution prepared to contain 1 ppm iron liquid.

Test solution v: A solution prepared to contain 3 ppm of iron in the solution with prescription number a.

Similar tests were also conducted for prescription codes d and f.

According to the measurement results, in all cases of prescription codes a, d, and f, the test solutions ■ and ■° exhibit a red color and a
Spectra showing maximum absorption near the test solution were obtained, but like test solution 1, test solutions IV and V remained colorless and no absorption was observed, indicating that the iron ions were blocked by EDTA and did not combine with thiocyanine ions. I understand.

This indicates that in the case of test solutions IV and V, the iron ions were bound to the metal sequestering agent and were unable to react with other substances and were sequestered (inactivated).

2) Sequestration of calcium ions When EBT (Elio Frombrasov T) and calcium form a complex, it appears red.

However, when EDTA is present, the bond between EDTA and calcium ions is stronger than the bond between EBT and calcium ions, so EBT and calcium ions cannot form a complex, and no red color develops.

Therefore, using this property, we observed whether calcium ions were actually sequestered by this preparation.

20ml each of the following three tests II, V [and ■]
into a test tube with a stopper, and add 5 mL of ammonium chloride-ammonia buffer solution and 1 fflo and 2 x g of 0.5% methanol solution of EBT (Elio from Black T).

For these test solutions, 700 to 450n using a spectrophotometer.
Absorption at a wavelength of I11 was measured.

Test solution I: Purified water test solution ■: Calcium standard solution (CaCO, 300
(liquid containing ppca) Test solution ■: CaC0 = 3 in the solution of prescription code a
A solution prepared to contain 00 ppa+.

Similar tests were also conducted for prescription codes d and g.

According to the measurement results, in all cases of prescription codes a, d, and g, maximum absorption near 550 nm was observed in test solution ① due to the formation of a complex between EBT and calcium.
This was not observed in Test Solution (1) and Test Solution 1 (blank test), which showed a different absorption spectrum pattern.

This indicates that calcium ions were sequestered by the metal sequestering agent contained in test solution (1) and that calcium could not react with EBT.

Example 3 An example of a liquid formulation is shown below.

B) Powder formulation (dissolved in each component contained in 1 package: 50%) Sodium hexametaphosphate 0.05 gED
TA・2Na O, 15g boric acid
0.15 g borax
0,081 g sodium chloride
0.29 g of the raw material components of the above recipe were ground in advance, and the prescribed amounts of each were taken out according to the recipe, and the powder was obtained by stirring and mixing in a mixer.

Mouth) Granule formulation (amount of each component contained in one tablet: dissolved in 50πQ) Sodium hexametaphosphate 0.05 g EDTA
・2Na 0.10 g boric acid
0.15 g borax
0.060 g sodium chloride
0.31 g Macrogol 40oO (lubricant) 0.0075 g The raw ingredients of the above recipe were crushed in advance, the prescribed amounts of each were taken according to the recipe, stirred and mixed in a mixer, and water:ethanol-1 : The mixture was kneaded with a mixed solvent of 1, passed through a mesh, heated and dried to obtain granules.

c) Tablet formulation (amount of each ingredient contained in 1 package; dissolved in 50xI2)
Sodium hexametaphosphate 0.05 gEDTA
・2Na 0.075 g boric acid
0.15 g borax
0.047g Sodium chloride 0.
33 g The raw material components of the above formulation were crushed in advance, and the prescribed amounts of each were taken according to the prescription, stirred and mixed in a mixer, granulated, and then compressed to obtain tablets.

[Brief explanation of the drawing]

1 and 2 show the 55% measured in Example 1.
Absorption curves from 0nra to 400ni are shown.

Claims (1)

[Claims] 1. A preparation for preparing a storage solution for soft contact lenses, which is characterized by containing a sequestrant, an isotonizing agent, and a pH buffer.