JP2001318350A - Solution for contact lens - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a solution for contact lenses which contains an antiseptic having a cation group, has an excellent antiseptic power and, further, sufficiently suppresses the adsorption of the antiseptic to the contact lenses. SOLUTION: The solution for contact lenses is featured in that the solution contains the antiseptic having the cation group, a nonionic surfactant and acidic mucopolysaccharides and more preferably further contains cyclodextrins. This solution for contact lenses is prepared by compounding the antiseptic having the cation group, the nonionic surfactant and the acidic mucopolysaccharides, by which the suppression of adsorption of the antiseptic having the cation group to the contact lenses is made possible while antiseptic power is maintained. This solution is useful as the solution for contact lenses to be used by contact lens wearing persons and particularly above all soft contact lens wearing persons.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a contact lens wearer, and more particularly to a contact lens solution used by a soft contact lens wearer. More specifically, the present invention relates to a preservative having a cationic group and a nonionic surfactant. The present invention relates to a solution for a contact lens in which a preservative having a cationic group is suppressed from adsorbing to a contact lens, particularly to a soft contact lens by using an agent and an acidic mucopolysaccharide, particularly sodium chondroitin sulfate, in combination.

[0002]

2. Description of the Related Art Conventionally, as preservatives for eye drops, benzalkonium chloride,
Compounds having a cationic group such as benzethonium chloride and chlorhexidine gluconate, chlorobutanol, p-aminobenzoic acid ester, sorbic acid and the like are used alone or in an appropriate combination of two or more.

Among these preservatives, preservatives having a cationic group, in particular, have been widely used as preservatives for eye drops because of their excellent preservative power. However, these preservatives are useful for contact lenses, especially for soft lenses. Because of the high affinity with contact lenses, if eye drops containing these preservatives are applied to the eye while wearing the contact lenses, the preservatives in the eye drops will be adsorbed and accumulate sequentially in the contact lenses There was a problem.

Therefore, various means have been proposed for preventing preservatives having a cationic group in eye drops from adsorbing to contact lenses. For example, Japanese Patent Application Laid-Open No. 52-109953 discloses an eye drop containing a preservative having a cationic group. There has been proposed a method of adding a nonionic surfactant to the solution, but in this case, if a sufficient amount of the nonionic surfactant is added to the adsorption suppressing effect, there is a problem that sufficient preservative power cannot be obtained. there were.

[0005] The present invention has been made in view of the above circumstances,
An object of the present invention is to provide a contact lens solution which contains a preservative having a cationic group and has not only an excellent preservative power but also a sufficiently suppressed preservative from adsorbing to a contact lens.

[0006]

Means for Solving the Problems and Embodiments of the Invention The present inventors have conducted intensive studies in order to achieve the above object, and as a result, as shown in Examples described later, a preservative having a cationic group The contact lens solution containing a nonionic surfactant, further, by simultaneously mixing an acidic mucopolysaccharide such as chondroitin sodium sulfate, adsorption of the preservative to contact lenses, particularly soft contact lenses, is suppressed. At the same time, they have found that excellent preservative power can be obtained, and have completed the present invention.

That is, the present invention is characterized by comprising a preservative having a cationic group, a nonionic surfactant, and an acidic mucopolysaccharide, and more preferably further comprises a cyclodextrin. A contact lens solution is provided.

Hereinafter, the present invention will be described in more detail. The contact lens solution of the present invention comprises a preservative having a cationic group, a nonionic surfactant, and an acidic mucopolysaccharide, whereby a preservative having a cationic group is added to a contact lens, particularly to a soft contact lens. It is a solution used by contact lens wearers, that is, a solution to be applied to the eyes wearing contact lenses, a daily care for contact lenses themselves, and a solution to be used at the time of wearing. Things.

Here, as the preservative having a cationic group, which is the first essential component of the present invention, known ones can be used, for example, benzalkonium chloride, benzethonium chloride, cetyldimethylbenzylammonium chloride, Domiphen bromide, 3- (trimethoxysilyl) propyldimethyloctadecyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, stearyl trimethyl ammonium chloride, distearyl dimethyl ammonium chloride, stearyl pentaethoxy ammonium chloride, cetyl pyridinium chloride, cetyl pyridinium bromide, odor Quaternary ammonium salts such as lauroyl isoquinolium bromide; chlorhexidine hydrochloride, chlorhexidine gluconate, dodecylguanidine hydrochloride, polyhexamethylene biguanide hydrochloride Emissions, 6-acetoxy-2,4-dimethyl-meta preservative such as guanidine can be cited, such as dioxane, which can be used singly or in a combination of two or more as appropriate. In the case of the present invention, suitability as a preservative to be mixed with a solution to be applied to the eye,
Considering the preservative power and the like, a quaternary ammonium salt type is particularly preferable among these.

The amount of the preservative in the contact lens solution of the present invention is not particularly limited, but is usually 0.001 to 0.1% (mass / volume%, hereinafter the same), preferably 0 to 0.1% of the whole solution. 0.005 to 0.02% is preferred. If it is less than 0.001%, the preservative may not be sufficiently effective by the preservative, and if it exceeds 0.1%, for example, when the above solution is applied to the eye, it may cause irritation and impair the feeling of use. There is.

The type of the non-ionic surfactant which is the second essential component of the present invention is not particularly limited, and examples thereof include higher fatty acid esters such as water-soluble polyoxyethylene hydrogenated castor oil, and polyoxygenated surfactants. Examples thereof include higher fatty acid esters of ethylene sorbitan and fatty acid esters of sucrose. Specifically, for example, polyoxyethylene (p = 6
0) Hardened castor oil, polyoxyethylene (p = 20) sorbitan monooleate and the like. More specifically, for example, as a polyoxyethylene hydrogenated castor oil, HCO-40, HCO-50, manufactured by Nikko Chemicals Co., Ltd.
As a polyoxyethylene sorbitan monooleate such as HCO-60, TO-10 manufactured by Nikko Chemicals Co., Ltd.
And the like. These can be used alone or in combination of two or more.

The amount of the surfactant in the contact lens solution of the present invention is not particularly limited, but is usually 0.001 to 1%, preferably 0.01 to 0.3%, based on the whole solution. It is suitable. If the concentration is lower than 0.001%, the effect of suppressing the adsorption of the preservative, for example, to soft contact lenses may not be sufficiently obtained.
At concentrations higher than%, the preservative power may be reduced.

Examples of the acidic mucopolysaccharide, which is the third essential component of the present invention, include hyaluronic acid, chondroitin sulfate, chondroitin polysulfate, keratosulfate, keratopolysulfate, heparin, heparitin sulfate, teichronic acid and salts thereof. These can be used alone or in an appropriate combination of two or more. In the case of the present invention, among these, particularly preferred acidic mucopolysaccharides include chondroitin sulfate, chondroitin polysulfate, and salts thereof.

The amount of the acidic mucopolysaccharide in the contact lens solution of the present invention is not particularly limited, but is usually preferably 0.001 to 1 of the entire solution.
%, More preferably 0.05 to 0.5%,
In this range, particularly excellent adsorption suppressing effect and antiseptic power can be obtained.

The contact lens solution of the present invention may further comprise a cyclodextrin, and the contact lens solution derived from a nonionic surfactant, an acidic mucopolysaccharide or the like incorporated in the contact lens solution of the present invention. This is more preferable since the base odor of can be suppressed well. Here, the cyclodextrins include cyclodextrins and cyclodextrin derivatives having a saccharide cyclic structure of cyclodextrin necessary for inclusion, and examples of cyclodextrins include α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and the like. Dextrin and δ-cyclodextrin; and as the cyclodextrin derivative, for example, methylated cyclodextrin, hydroxyethylated cyclodextrin, maltosyl-α-cyclodextrin, hydroxyethyl-β-cyclodextrin, triacetyl- β-cyclodextrin and the like, among which α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, δ-cyclodextrin, methylated cyclodextrin Trilin and hydroxyethylated cyclodextrin are more preferably used, and these can be used alone or in an appropriate combination of two or more.

The amount of the cyclodextrin in the contact lens solution of the present invention is not particularly limited, but is usually preferably 0.03% of the total solution.
１1%, more preferably 0.03 to 0.5%.
If the content is less than 0.03%, the effect of the cyclodextrin compound may be insufficient.
Problems may occur in the storage stability of the solution under low temperature conditions.

The contact lens solution of the present invention has a pH
Adjusting to 5.0 to 8.0 is preferable. Outside this range, eye irritation may occur or unfavorably affect, for example, physical properties of the soft contact lens.

The osmotic pressure of the contact lens solution of the present invention is preferably adjusted to an osmotic pressure ratio of 0.1 to 5, more preferably 0.5 to 2.5. Outside of this range, eye irritation may occur or unfavorably affect, for example, the physical properties of the soft contact lens.

The solution for contact lenses of the present invention may contain, if necessary, various components commonly used for preparing ophthalmic compositions such as eye drops, as long as the effects of the present invention are not hindered. Can be blended in its usual usage.

Such components include, for example, dipotassium glycyrrhizinate, allantoin, berberine chloride,
Anti-inflammatory agents such as berberine sulfate, sodium azulene sulfonate, zinc sulfate, zinc lactate, lysozyme chloride, flavin adenine dinucleotide sodium (active vitamin B ₂ ), pyridoxine hydrochloride (vitamin B ₆ ), cyanocobalamin (vitamin B ₁₂ ), Vitamins such as vitamin E acetate, panthenol, calcium pantothenate, sodium pantothenate, retinol acetate, retinol palmitate (vitamin A palmitate), potassium L-aspartate, magnesium L-aspartate, magnesium magnesium L-aspartate ( Equivalent mixture), aminoethylsulfonic acid (taurine), epsilon aminocaproic acid, amino acids such as L-glutamic acid, sodium L-glutamate, diphenhydramine hydrochloride, maleic acid Antihistamines such as chlorpheniramine acid, decongestant components such as epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, naphazoline hydrochloride, naphazoline nitrate, phenylephrine hydrochloride, tetrahydrozoline hydrochloride, sulfamethoxazole, sulfamethoxazole sodium, sulfisoxa Sulfur agents such as sol and sulfisomidine sodium, antiallergic agents such as cromoglycic acid, sodium cromoglycate, tranilast and potassium pemirolast, active ingredients such as neostigmine methyl sulfate, and boric acid, borax, phosphoric acid, and phosphoric acid PH adjusters and buffers such as sodium hydrogen, sodium dihydrogen phosphate, crystalline sodium phosphate, potassium dihydrogen phosphate, citric acid, sodium citrate, hydrochloric acid, sodium hydroxide, sodium chloride, chloride Inorganic salts such as lium, calcium chloride, sodium bicarbonate, sodium carbonate, dried sodium carbonate, magnesium sulfate, etc., tonicity agents such as glycerin, ethylenediaminetetraacetic acid, disodium ethylenediaminetetraacetate (sodium edetate), polyoxyethylene Solubilizing agents such as oxypropylene block copolymer (for example, “Poloxamer 407”, manufactured by NOF Corporation) and propylene glycol;
Antioxidants such as dibutylhydroxytoluene (BHT) and ascorbic acid; methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, hyaluronic acid, sodium hyaluronate, glucose, etc. Thickener, menthol,
Additives such as refreshing agents such as camphor and borneol, and local anesthetics such as chlorobutanol,
These can be blended within a range that does not impair the effects of the present invention.

The solution for the contact lens of the present invention is not particularly limited in its dosage form, preparation method and the like. Examples thereof include eye drops, eyewashes, contact lens mounting solutions, preservatives, and detergents. Can be prepared according to the conventional method.

The use of the contact lens solution of the present invention is not particularly limited, and it can be applied to eye drops while wearing a contact lens, regardless of whether it is for medical use or for general use, Eyewash for contact lenses that can wash eyes while wearing contact lenses,
It can be used as a contact lens mounting solution, a contact lens preservative, and a contact lens cleaning agent according to these conventional methods. In particular, the contact lens solution of the present invention can reduce eye fatigue and discomfort when wearing a soft contact lens, a frequently exchangeable soft contact lens, and a daily exchangeable soft contact lens. It is particularly useful as an ophthalmic solution for a soft contact lens that can be instilled in the state of wearing a pill.

[0023]

According to the contact lens solution of the present invention, a preservative having a cationic group, a nonionic surfactant and an acidic mucopolysaccharide such as sodium chondroitin sulfate are blended to obtain a sufficient preservative power. It is possible to suppress the preservative having a cationic group from adsorbing to a contact lens, particularly a soft contact lens, while maintaining the above condition. Therefore, the contact lens solution of the present invention is useful as a contact lens solution used when a contact lens wearer, particularly a soft contact lens wearer, wears a contact lens and handles the contact lens.

[0024]

Next, the present invention will be described more specifically with reference to examples and comparative examples, but the present invention is not limited to the following examples.

First, test methods performed in Examples and Comparative Examples of the present invention will be described below.

<Adsorption Test of Preservatives on Soft Contact Lenses> Based on four classifications of soft contact lenses by the FDA (US Food and Drug Administration), representative lenses such as Sequence (Bausch & Lomb Japan) and Softmu (Ltd.) ) Nippon Contact Lens), High Flow Ace (HOYA Co., Ltd.) and Accuview (Johnson & Johnson Medical Co., Ltd.), and add one lens to 5 ml of eye drops (solution for contact lens).
After immersion at 7 ° C. for 7 days, the amount of the preservative in the remaining liquid was quantified by the HPLC method. The same treatment was carried out with the ophthalmic solution in which the lens was not immersed, and the adsorption ratio for each lens was calculated from the ratio to the control.

<Antiseptic Test> Eschercha co.
li, Psedomonas aeruginosa,
Staphlococcus aureus was used as a test bacterium in accordance with the preservation efficacy test described in the Japanese Pharmacopoeia.

[Examples 1 to 11 and Comparative Examples 1 to 11] Each component was sterilized and purified water so as to have the composition shown in Table 1 (composition unit: w / v% (mass / volume%), the same applies hereinafter). To prepare aqueous solutions of Examples and Comparative Examples. Each of the obtained aqueous solutions was sterile-filtered, and the above-mentioned adsorption test and sterility test (preservation test) were carried out. The results of Examples and Comparative Examples having the same numbers were compared and evaluated according to the following criteria. The results are also shown in Table 1.

<Evaluation Criteria> ：: Example is superior ○: Example and Comparative Example are equivalent ×: Comparative Example is superior

[0030]

[Table 1] Note) TO-10 ^{* 1)} : Polyoxyethylene (20) sorbitan monooleate, manufactured by Nikko Chemicals Co., Ltd. HCO-60 ^{* 2)} : Polyoxyethylene (60) hardened castor oil, manufactured by Nikko Chemicals Co., Ltd.

Examples 12 to 26 and Comparative Examples 12 to 1
5] After dissolving the components shown in Tables 2 to 4 in sterile purified water, dilute hydrochloric acid or sodium hydroxide was used to dissolve each of the pH values in the table.
The solution was subjected to aseptic filtration to prepare a preparation (ophthalmic solution, contact lens mounting solution). Each of the obtained preparations was subjected to the above-mentioned adsorption test and sterility test (antiseptic test), and these results were evaluated according to the following evaluation criteria. The results are shown in Tables 2 to 4. In the above-mentioned preparations, those containing α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin were able to suppress the base odor well.

<Evaluation Criteria for Preservative Adsorption Test for Soft Contact Lenses> A: The average adsorption rate of the preservative to the four lenses is less than 1% B: The average adsorption rate of the preservative to the four lenses is 1% Not less than 5% C: the average adsorption rate of the preservative to the four lenses is 5% or more and less than 10% D: the average adsorption rate of the preservative to the four lenses is 10%
that's all

<Evaluation Criteria for Antiseptic Test> A: The time required for killing fungi is within 5 days. B: The time required for killing fungi is 6 to 10 days. C: The time required for killing fungi is 11 to 20 days. : More than 21 days to kill fungi

As the contact lens solution,
In both tests, the evaluation is preferably B or more, and more preferably A.

[0035]

[Table 2] Note) TO-10 ^{* 1)} : Polyoxyethylene (20) sorbitan monooleate, manufactured by Nikko Chemicals Co., Ltd. HCO-60 ^{* 2)} : Polyoxyethylene (60) hardened castor oil, manufactured by Nikko Chemicals Co., Ltd.

[0036]

[Table 3] Note) TO-10 ^{* 1)} : Polyoxyethylene (20) sorbitan monooleate, manufactured by Nikko Chemicals Co., Ltd. HCO-60 ^{* 2)} : Polyoxyethylene (60) hardened castor oil, manufactured by Nikko Chemicals Co., Ltd.

[0037]

[Table 4] Note) TO-10 ^{* 1)} : Polyoxyethylene (20) sorbitan monooleate, PVA ^{* 2} manufactured by Nikko Chemicals Co., Ltd .: Polyvinyl alcohol ("Gohsenol E" ⁾
G-05 ", manufactured by Nippon Synthetic Chemical Industry Co., Ltd.) PVP ^{* 3)} : Polyvinylpyrrolidone (" Korydone K-2 " ⁾
5 ", manufactured by BASF Japan Ltd.) HPMC ^{* 4)} : Hydroxypropyl methylcellulose (" Metroze 65SH-1500 ", manufactured by Shin-Etsu Chemical Co., Ltd.) MC ^{* 5)} : Methylcellulose (" Metroze SM-2 " ⁾
5 ", manufactured by Shin-Etsu Chemical Co., Ltd.)

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C08L 5/00 C08L 5/00 5/16 5/16 // A61K 31/14 A61K 31/14 47/14 47/14 F-term (reference) 2H006 DA08 DA09 4C076 AA12 BB24 CC31 DD08F DD19R DD49R EE30 EE37 EE39 FF15 FF16 FF18 4C206 AA01 AA02 FA41 HA31 KA01 MA02 MA03 MA05 MA37 MA78 NA11 ZA33 ZB35 4J002 AB05Y05 BB05YX

Claims (2)

[Claims] 1. A contact lens solution comprising a preservative having a cationic group, a nonionic surfactant, and an acidic mucopolysaccharide. 2. The contact lens solution according to claim 1, further comprising a cyclodextrin.