JP2002316926A - Ophthalmic composition for contact lens and method for mitigating ocular irritation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an ophthalmic composition for contact lenses causing slight irritation to wearers of the contact lenses, suppressing effects on the lenses and having excellent antiseptic effects and to enable mitigation of ocular irritation with drugs contained in the ophthalmic composition for the contact lenses especially when the contact lenses are worn, instillation is carried out during wearing of the contact lenses or the eyes are washed after removing the contact lenses. SOLUTION: This ophthalmic composition for the contact lenses comprises trometamol as an antiseptic without containing a cationic antispectic.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an ophthalmic composition applicable to a contact lens user (hereinafter referred to as an ophthalmic composition for a contact lens). Of ophthalmic compositions for contact lenses and eye drops for contact lenses, contact lens mounting solutions or eyewashes for contact lenses that can provide safe and excellent preservative effects to the eyes without blending preservatives The present invention relates to a method for alleviating eye irritation during application.

[0002]

2. Description of the Related Art Conditions for preservatives to be added to ophthalmic compositions such as eye drops for contact lenses include (1) efficacy (having a bactericidal action against bacteria and fungi) and (2) stability (drugs and drugs). Preservatives themselves are stable against long-term storage without causing any change in formulation with additives. (3) Safety (does not cause irritation or damage to ocular tissues, does not affect physical properties of contact lenses) Is desired.

[0003] Among eye drops commercially available in Japan, 61.8% (60.5% of benzalkonium chloride, 60.5% of gluconic acid, etc.) use a cationic surfactant represented by benzalkonium chloride having a high preservative effect. Chlorhexidine 1.3
%) And accounted for more than half (Japan contact lens Journal 35 p238~241, 1993 years).

[0004] However, if eye drops containing these preservatives are frequently instilled or if a person with a corneal disorder is instilled,
May cause side effects such as promoting corneal disorders (Ophthalmology 31 p43-48 1989, ophthalmology 33 p
533-538 (1991), and safety is a concern.

[0005] Particularly, a contact lens wearer is in a state where the cornea is easily damaged, and is easily affected by a preservative. Moreover, since the preservative stays between the cornea and the contact lens for a long time, eye irritation is more likely to occur. Further, in the case of a soft contact lens, the preservative is easily adsorbed to the lens, so that not only stimulation is further promoted, but also deterioration of the lens such as clouding occurs.

[0006] A method has been disclosed in which a cationic preservative is included in cyclodextrin to suppress adsorption to a soft contact lens (Japanese Patent Laid-Open No. 08-17).
Due to the inclusion of cyclodextrin, the effect on the effect may be affected depending on the type of component.

[0007] In addition, the method using in combination with an adsorption inhibitor such as a nonionic surfactant has a problem that the preservative power is reduced.

[0008] Accordingly, there has been a need for an ophthalmic composition which is suitable for contact lens users and has excellent antiseptic properties.

Further, eye drops, contact lens mounting liquid,
Eyewashes are usually mixed with drugs, but depending on the type of drug, eye irritation may be felt when instilling or wearing contact lenses. In the case of wearing, there is a case where the irritation is noticeable in some cases, and it has been desired to alleviate the eye irritation by such a drug.

[0010]

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and is intended for a contact lens having less stimulus to a contact lens wearer, less influence on a lens, and an excellent antiseptic effect. A method for alleviating eye irritation to reduce eye irritation caused by a drug contained in an ophthalmic composition for a contact lens when the ophthalmic composition and a contact lens are worn, and when the eye wash is performed after instilling or removing the eye when the contact lens is worn. The purpose is to provide.

[0011]

Means for Solving the Problems and Embodiments of the Invention The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, an aqueous solution containing trometamol has excellent preservative power, Furthermore, they have found that they have excellent safety even when used when wearing contact lenses. Even more surprisingly, they have found that trometamol reduces the eye irritation of the drug, leading to the completion of the present invention.

That is, the present invention provides an ophthalmic composition for a contact lens, comprising tromethamol. Further, the present invention provides an ophthalmic composition for contact lenses, which comprises trometamol as a preservative. Here, it is more preferable that the ophthalmic composition for a contact lens does not contain a cationic preservative, and it is even more preferable that the ophthalmic composition for a contact lens is a soft ophthalmic composition. Further, the present invention is a method for alleviating eye irritation by a drug contained in a contact lens ophthalmic composition used as a contact lens eye drop, a contact lens mounting solution or a contact lens eyewash, Provided is a method for alleviating eye irritation, characterized by alleviating eye irritation by incorporating trometamol.

Hereinafter, the present invention will be described in more detail. The ophthalmic composition for a contact lens according to the present invention contains tromethamol. Here, in the ophthalmic composition for a contact lens of the present invention, the content of trometamol is not particularly limited, but usually,
It is preferably 0.1 to 5% by mass / volume (hereinafter, w / v%), more preferably 0.5 to 5% w / v, based on the total amount of the composition.
v%, more preferably 1 to 5 w / v%. Within this range, it is possible to easily obtain a composition having the desired preservative power of the present invention and having no eye irritation.

The ophthalmic composition for contact lenses of the present invention can maintain excellent antiseptic power even without the addition of a preservative of a cationic surfactant by containing trometamol. The blending amount of the fungicide is preferably 0 to 0.001 w / v%, more preferably 0 to 0.0005 w / v%, and particularly preferably, no cationic fungicide can be used. Here, more specific examples of the cationic bactericide include benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, and the like.

Further, in the present invention, when a drug is contained in an ophthalmic composition for a contact lens used as an eye drop for a contact lens, a contact lens mounting solution or an eyewash for a contact lens, by using tromethamol together, The eye irritation of the above drugs can also be reduced. More specifically, examples of such drugs include decongestants (naphazoline hydrochloride, tetrahydrozoline hydrochloride, phenylephrine hydrochloride, etc.), anti-inflammatory and astringents (neostigmine methyl sulfate, ε-aminocaproic acid, allantoin, berberine chloride, zinc sulfate) , Lysozyme chloride), antihistamines (diphenhydramine hydrochloride, isotipendyl hydrochloride, chlorpheniramine maleate, etc.),
Water-soluble vitamins (active vitamin B ₂ , vitamin B ₆ ,
Vitamin B ₁₂ ), fat-soluble vitamins (vitamin A (eg, retinol acetate, retinol palmitate), vitamin Es (tocopherol acetate (eg, d-α-acetic acid)
Tocopherol)), amino acids (potassium L-aspartate, magnesium L-aspartate, aminoethylsulfonic acid, sodium chondroitin sulfate, etc.),
A sulfa drug, a bactericide (sulfur, isopropylmethylphenol, hinokitiol, etc.) and a local anesthetic (lidocaine, lidocaine hydrochloride, procaine hydrochloride, dibucaine hydrochloride, etc.) can be appropriately compounded. These can be used alone or in an appropriate combination of two or more. In the case of the present invention, among them, particularly when ε-aminocaproic acid, chlorpheniramine maleate or the like is contained, it is effective in alleviating eye irritation.

The content of the above drug in the ophthalmic composition for contact lenses of the present invention is not particularly limited, but is usually 0.001 to 10 with respect to the total amount of the composition.
The w / v% is preferably 0.003 to 5 w / v%, more preferably 0.005 to 4 w / v%.
If the content is too small, sufficient drug efficacy may not be obtained, and if it is too large, it may be difficult to sufficiently reduce eye irritation caused by the drug. For the same reason, the content ratio to tromethamol is tromethamol: drug (mass ratio) = 5000: 1 to 1:20, preferably 1000: 1 to 1:10, and more preferably 500:
A ratio of 1-1: 8 is preferred.

The ophthalmic composition for contact lenses of the present invention is usually used in the preparation of ophthalmic compositions such as eye drops, wearing solutions, eyewashes, etc., in addition to the above components, as long as the effects of the present invention are not impaired. All buffers, dissolution aids, tonicity agents,
Various additives such as a stabilizer, a thickener, a chelating agent, a pH adjuster, and a cooling agent can be blended in a usual amount.

Examples of the buffer include boric acid or a salt thereof (borax or the like), citric acid or a salt thereof (sodium citrate or the like), phosphoric acid or a salt thereof (sodium monohydrogen phosphate or the like), tartaric acid or a salt thereof. Salts (such as sodium tartrate), gluconic acid or its salts (such as sodium gluconate), acetic acid or its salts (such as sodium acetate), various amino acids (epsilon-aminocaproic acid, potassium aspartate,
Aminoethylsulfonic acid, glutamic acid, sodium glutamate, etc.) or a combination thereof.
Particularly, boric acid or a salt thereof is preferable because it enhances the preservative effect of trometamol.

Examples of the solubilizing agent include polyoxyethylene (p = 60) higher fatty acid esters such as hydrogenated castor oil and polyoxyethylene (p = 60).
20) surfactants such as polyoxyethylene sorbitan higher fatty acid esters such as sorbitan monooleate;
Polyhydric alcohols such as propylene glycol and glycerin are exemplified. Preferably, a polyhydric alcohol is used. Examples of the tonicity agent include sodium chloride, potassium chloride and the like.

Examples of the stabilizer include sodium edetate, cyclodextrin, sulfite, citric acid or a salt thereof, dibutylhydroxytoluene and the like.
In particular, sodium edetate and dibutylhydroxytoluene are preferable because they enhance the preservative effect of trometamol.
It is preferable to mix 5 w / v%, more preferably, 0.
The range is from 01 to 0.2 w / v%. In addition, if it is dibutylhydroxytoluene, usually 0.001 to 0.1 w
/ V% is preferred, more preferably 0.00
It is in the range of 1 to 0.01 w / v%.

Examples of the thickener include polyvinylpyrrolidone, hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, polyvinyl alcohol, sodium hyaluronate, and chondroitin sulfate.

Examples of the pH adjuster include hydrochloric acid, citric acid or a salt thereof, boric acid or a salt thereof, phosphoric acid or a salt thereof,
Examples thereof include acetic acid or a salt thereof, tartaric acid or a salt thereof, sodium hydroxide, and potassium hydroxide. Examples of the cooling agent include menthol, camphor, borneol, geraniol, chlorobutanol, ethanol and the like.

The pH of the ophthalmic composition for contact lenses of the present invention is not particularly limited as long as it is ophthalmically acceptable, and is usually in the range of pH 5 to 9, preferably pH 6.
-8.5, more preferably pH 6.5-8.

The osmotic pressure of the ophthalmic composition for contact lenses of the present invention is preferably adjusted to 0.5 to 5 pressure ratio by a usual method, and more preferably to 0.8 to 2 pressure ratio.

The ophthalmic composition for contact lenses of the present invention is used as eye drops for contact lenses, contact lens mounting solutions, and eyewash for contact lenses. In particular, it is useful as an ophthalmic composition for soft contact lenses, such as eye drops for soft contact lenses, soft contact lens mounting solutions, and eyewash for soft contact lenses.

The method of preparing the ophthalmic composition for contact lenses of the present invention is not particularly limited, and can be prepared according to the conventional methods of eye drops, contact lens mounting solutions, and eyewashes.

The dose and amount of the ophthalmic composition for contact lenses of the present invention are not particularly limited as long as they are within an ophthalmologically acceptable range.
It is preferred that 1 to 3 drops be administered 4 to 6 times a day.

[0028]

According to the present invention, there is obtained an ophthalmic composition for a contact lens having little irritation to a wearer of the contact lens, suppressing the influence on the lens, and having an excellent preservative effect. The eye irritation caused by the drug contained in the ophthalmic composition for contact lenses can be mitigated when the eye is worn, when the eye is instilled when the contact lens is worn, or when the eye is washed after removing the contact lens. Accordingly, the ophthalmic composition for contact lenses of the present invention is particularly suitable for eye drops for soft contact lenses,
It is useful as an ophthalmic composition for soft contact lenses, such as a soft contact lens mounting solution and an eyewash for soft contact lenses.

[0029]

EXAMPLES The present invention will be described in more detail with reference to examples and comparative examples, but the present invention is not limited to these examples.

Examples 1 and 2 and Comparative Examples 1 to 3 The compositions shown in Table 1 (mixing amount: g / 100 mL, pH 7.0)
An eye drop for contact lens was prepared according to a conventional method, and tests 1 to 3 shown below were performed. The results are also shown in Table 1.

[0031]

[Table 1]

<Test 1> Preservative Efficacy Test The compositions shown in Table 1 were subjected to a preservative efficacy test according to the 13th revised Japanese Pharmacopoeia / Preservative Efficacy Test Method. That is, the following bacteria and fungi were added to the composition shown in Table 1 so as to be 10 ⁵ to 10 ⁶ per mL, and 25
C., and after 14 days and 28 days, each 1 mL of the solution inoculated with the bacteria was cultured. Then, the number of viable bacteria was measured, and the survival rate with respect to the number of inoculated bacteria was calculated.

Bacteria Pseudomonas aeruginosa ATCC 9027 Escherichia coli ATCC 8739 Staphylococcus aureus ATCC 6538 Fungus Candida albicans ATCC 10231 Aspergillus ATCC

The criterion for judging the preservative efficacy is that the survival rate after 14 days for bacteria is 0.1% or less of the inoculated bacterial count, that for fungi is the same or lower than the number of inoculated bacteria, and that the survival rate after 28 days is 14 days for bacteria. , And for fungi it is at or below the level of the number of inoculated bacteria. A sample satisfying all of these criteria was evaluated as ○, and a sample not satisfying at least one was evaluated as ×.

The culture was carried out on bacteria against SCDLP agar medium (Soybean Case Digest).
Agar with Lerctin & Pol
ysorbate80) (manufactured by Nippon Pharmaceutical Co., Ltd.), and the fungus includes GPLP agar medium (Glucose Peptone).
Agar with Lerctin & Pol
ysorbate80) (manufactured by Nippon Pharmaceutical Co., Ltd.). Table 2 shows the results.

[0036]

[Table 2]

As is clear from the results in Table 2, Example 1
The aqueous solution containing trometamol has excellent preservative power, and in Example 2, the high preservative power is maintained even when a drug or a polymer compound is blended. On the other hand, in Comparative Example 1 containing no preservative, sufficient preservative power could not be obtained, and the criteria could not be reached.

<Test 2> Evaluation of Feeling for Use For each composition shown in Table 1, three males and females wearing soft contact lenses were panelists, and eye irritation when instilled was evaluated based on the following evaluation criteria. As a result, in Examples 1 and 2, no one felt any irritation. On the other hand, when chlorhexidine gluconate (Comparative Example 2) and benzalkonium chloride (Comparative Example 3) were used as preservatives, irritation occurred. I showed you feel.

<Evaluation Criteria> ：: 0 people felt eye irritation ×: 1 or more people felt eye irritation

<Test 3> Physical Properties of Lens (Haze) The effect of each composition shown in Table 1 on the physical properties of the soft contact lens was evaluated. The soft contact lens was immersed in physiological saline mixed with lysozyme (major protein in tears) for 1 hour, further immersed in each composition for 1 hour, and washed by boiling. The change of the lens after repeating this operation 10 times was observed. As a result, as shown in Table 1, in Examples 1 and 2 and Comparative Example 1, there was no effect on the lens, whereas in Comparative Examples 2 and 3, discoloration of the lens was observed. , And those that did not exist are indicated by ○).

[Examples 3 to 9] Eye drops having the compositions shown in Table 3 were prepared according to a conventional method, and the above tests 1 to 3 were evaluated. As a result, good results were obtained in all cases.

[0042]

[Table 3]

Example 10 (Contact Lens Attaching Solution) To sterilized purified water, 1.0 g of trometamol and an appropriate amount of hydrochloric acid were added to adjust the pH to 7.0, and then polyvinyl alcohol was added.
0 g was added and dissolved by heating at 80 ° C. To this, 0.01 g of sodium edetate, 1.
0 g, potassium L-aspartate 0.5 g, sodium chloride 0.2 g, hydroxypropyl cellulose 1.0
g, and the mixture was stirred and mixed, and then cooled. Furthermore, l-menthol 0.001 to 0.5 g of propylene glycol was previously prepared.
g, dl-camphor 0.001 g and d-borneol 0.001 g were added, and the total amount was 100
mL, followed by filtration to obtain a contact lens mounting solution.

Example 11 (Eyewash) 1.0 g of trometamol, 0.2 g of sodium chloride, 0.01 g of pyridoxine hydrochloride, 0.001 of berberine chloride
5 g, dipotassium glycyrrhizinate 0.025 g, chlorpheniramine maleate 0.003 g, and sodium edetate 0.01 g were added to sterilized purified water heated to 70 ° C., stirred, mixed, and cooled. Further, after adding an appropriate amount of diluted hydrochloric acid to adjust the pH to 7.5, a solution prepared by dissolving 0.3 g of chlorobutanol, 0.03 g of l-menthol, and 0.01 g of dl-camphor in 1.0 g of propylene glycol in advance was used. In addition, the total amount was adjusted to 100 mL and filtered to obtain an eyewash.

The tests 1 and 3 described above were evaluated for the ophthalmic compositions (contact lens mounting solution, eyewash) of Examples 10 and 11, and good results were obtained. In addition, in the above Test 2, instead of instilling the eye with the soft contact lens attached, except for washing the eye after wearing the soft contact lens or removing the soft contact lens, the feeling of use was similarly evaluated, None of them felt eye irritation.

Continuation of the front page F term (reference) 2H006 DA08 DA09 4C058 AA09 BB07 CC02 JJ06 4C206 AA01 FA03 MA03 MA05 MA37 NA14 ZA33

Claims (5)

[Claims] 1. An ophthalmic composition for a contact lens, comprising trometamol. 2. An ophthalmic composition for contact lenses, comprising trometamol as a preservative. 3. The composition according to claim 1, which does not contain a cationic preservative.
Or the ophthalmic composition for contact lenses according to 2. 4. The ophthalmic composition for a contact lens according to claim 1, which is for a soft contact lens. 5. A method for alleviating eye irritation caused by a drug contained in an ophthalmic composition for a contact lens used as an eye drop for a contact lens, a contact lens mounting solution or an eyewash for a contact lens, comprising trometamol. A method for alleviating eye irritation, which comprises the step of blending: