JP2001097865A - Ophthalmic composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an ophthalmic composition capable of obtaining a potent itchiness-improving effect right after its instillation. SOLUTION: This ophthalmic composition is characterized by including at least 1 kind of an allergic disease-treating agent selected from amlexanox, tranilast, pemirolast potassium and ketotifen fumalate, an anti-histamine agent such as chlorpheniramine maleate or diphenhydramine hydrochloride and a terpenoid such as menthol, camphor, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a therapeutic agent for allergic diseases, an antihistamine and a terpenoid.
The present invention relates to an ophthalmic composition which has a rapid and powerful itch-improving effect immediately after instillation and further suppresses discomfort during instillation.

[0002]

2. Description of the Related Art Conventionally, many drugs have been developed to suppress allergic reactions. For example, Tranilast suppresses mast cell degranulation associated with antigen-antibody reaction,
Suppresses release of chemical mediators such as histamine. As a result, the influx of antigen into the blood and the formation of immune complexes are prevented, and allergic reactions are suppressed. It has been clinically used as a prophylactic antiallergic agent from various administration routes.
Particularly in the ophthalmic field, it is used in Japan for diseases such as allergic conjunctivitis. However, tranilast suppresses mast cell degranulation, has no effect on the symptoms caused by already released chemical mediators, is inferior in aggressiveness, and several weeks before the onset of symptoms Needed to use.

[0003] Therefore, in order to impart an aggressive effect to an antiallergic ophthalmic composition containing an allergic disease therapeutic agent, an ophthalmic composition containing an antihistamine agent that exhibits an antagonistic action against released histamine has also been developed. Have been. When this ophthalmic composition is used, when it is instilled after the onset of allergic symptoms, a rapid itching improving effect can be obtained. However, itching cannot be completely suppressed due to a weak itch-improving effect, and the patient may scratch his eyes, causing inflammation of the mucous membrane of the eyes. The same is true for amlexanox, pemirolast potassium or ketotifen fumarate.

[0004]

DISCLOSURE OF THE INVENTION The present invention provides an ophthalmic composition having a strong itch-relieving effect immediately after instillation.

[0005]

Means for Solving the Problems The present inventor has made intensive studies to solve the above-mentioned problems, and as a result, by combining terpenoids with a specific allergic disease therapeutic agent and an antihistamine, the rapid action of the antihistamine has been achieved. It became possible to remarkably enhance the effect of improving itching, and it was possible to strongly suppress severe itching of eyes immediately after instillation, and furthermore, it was found that there was an effect of eliminating discomfort at the time of instillation, which led to the present invention. .

That is, the present invention provides an amlexanox,
Tranilast, at least one allergic disease therapeutic agent selected from potassium pemirolast or ketotifen fumarate, an antihistamine, and a terpenoid, a highly effective itch-improving effect, and an ophthalmic composition in which discomfort during eye drops is suppressed. provide.

The remedy for allergic diseases used in the present invention is amlexanox, tranilast, pemirolast potassium or ketotifen fumarate. These can be used commercially available ones.

Examples of the antihistamine used in the present invention include chlorpheniramine maleate, diphenhydramine hydrochloride, cyproheptadine hydrochloride, promethazine hydrochloride, and the like. Diphenhydramine is most preferred, and a commercially available product can be used.

The terpenoids used in the present invention include menthol, camphor, borneol, geraniol, cineol, linalool, eucalyptus oil, bergamot oil,
Fennel oil, rose oil and the like can be mentioned, but menthol, camphor, borneol and geraniol are preferred, and commercially available ones can be used.

The preferred content of the above-mentioned therapeutic agent for allergic diseases in the ophthalmic composition used in the present invention varies depending on the type, and amlexanox is usually 0.01 to 7%.
(W / v), tranilast is usually 0.02 to 10% (w
/ V), pemirolast potassium is usually 0.01 to 5%
(W / v), ketotifen fumarate is usually 0.01 to 6
% (W / v). Further, the content of the antihistamine to be blended is preferably 0.005 to 0.1% (w / v).
And more preferably 0.01 to 0.05% (w /
v). Further, the content of the terpenoids to be blended is preferably 0.0005 to 0.5% (w / v), more preferably 0.001 to 0.2% (w / v).

[0011] The pH of the ophthalmic composition of the present invention is not particularly limited as long as it is within an ophthalmologically acceptable range.
Adjust to 0-9.0. Also preferably, amlexanax is pH 6.8-7.8, and Tranilast is pH
7.0-8.0, pemirolast potassium, pH 7.5
~ 8.5, and ketotifen fumarate has a pH of 4.8.
Set to ~ 5.8.

The osmotic pressure of the ophthalmic composition of the present invention is usually adjusted to 0.5 to 5 pressure ratio by an ordinary method.
It is more preferable to adjust the pressure ratio to 0.8 to 2 pressure.

[0013] The ophthalmic composition of the present invention comprises a buffer as an additive, provided that the object of the present invention is solved.
Preservatives, thickeners, solubilizers, chelating agents, stabilizers,
You may add a tonicity agent, a pH adjuster, etc. Examples of the added buffer include borate buffer, phosphate buffer, carbonate buffer, acetate buffer and the like. Examples of the preservative include chlorobutanol, benzalkonium chloride, sodium dehydroacetate, cetylpyridinium chloride, phenethyl alcohol, p-hydroxybenzoates, benzethonium chloride and the like. As the thickener, methyl cellulose, hydroxyethyl cellulose,
Examples include carboxymethylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, propylene glycol, carboxymethylcellulose, chondroitin sulfate or a salt thereof. As dissolution aids, polyoxyethylene hydrogenated castor oil, polyethylene glycol, polysorbate 8
0, polyoxyethylene monostearate and the like. Examples of the chelating agent include sodium edetate, citric acid and the like. Examples of the stabilizer include sodium edetate, sodium bisulfite and the like. Examples of the tonicity agent include sodium chloride and potassium chloride. Examples of the pH adjuster include sodium hydroxide, potassium hydroxide, sodium carbonate, citric acid, phosphoric acid, acetic acid, hydrochloric acid, boric acid, and the like.

The dosage and administration of the ophthalmic composition of the present invention varies depending on the condition, age, etc. of the patient.
Four times, 1-2 drops are instilled each time.

[0015]

Industrial Applicability According to the present invention, ophthalmology containing a therapeutic agent for a specific allergic disease (amlexanox, tranilast, pemirolast potassium or ketotifen fumarate), an antihistamine (chlorpheniramine maleate, diphenhydramine hydrochloride), and terpenoids Composition was developed. As a result, the use of the ophthalmic composition of the present invention makes it possible to quickly suppress allergic symptoms immediately after instillation due to a strong itch-improving effect, and to exacerbate the conjunctival inflammation by scratching the patient's eyes. Can be prevented.
Further, in addition to the quick itching improving effect, it is possible to eliminate discomfort during instillation.

[0016]

Hereinafter, the present invention will be described with reference to examples.
The present invention is not limited to this. Table 3 to Table 13
Were prepared and evaluated as follows.
Compositions were prepared using conventional methods.

(1) Evaluation of Immediate Effect of Improving Itching and Degree of Improvement With respect to the ophthalmic compositions of Example 1 and Comparative Example 1, five adult males and females with a history of allergic symptoms were used as subjects, and allergic eyes were observed. The test was performed using two times when the symptoms developed. In the test method, first, one or two drops of Example 1 were instilled into both eyes when the onset occurred first, and then, after a certain period of time, Comparative Example 1 was instilled one or two drops into both eyes. Then, the degree of improvement of the symptoms (itch) was scored with time in accordance with the “criterion for itch improvement effect” described in Table 1, and the results are shown in FIG. Similarly, other ophthalmic compositions in Tables 3 to 13 were evaluated, and the most itch improvement (score) after 60 seconds was shown in the table.

[0018]

[Table 1]

(2) Discomfort at the time of instillation Evaluations based on the "criterion for discomfort" shown in Table 2 below were performed by the above subjects, and the most frequent improvement (score) results are shown in Tables 3 to 13. .

[0020]

[Table 2]

[0021]

FIG.

Referring to FIG. 1, the score of each subject was scored as follows, and the average value was used as the score. ：: 3 ○: 2 △: 1 ×: 0

[0023]

[Table 3]

[0024]

[Table 4]

[0025]

[Table 5]

[0026]

[Table 6]

[0027]

[Table 7]

[0028]

[Table 8]

[0029]

[Table 9]

[0030]

[Table 10]

[0031]

[Table 11]

[0032]

[Table 12]

[0033]

[Table 13]

Claims (3)

[Claims] 1. An ophthalmic composition comprising at least one therapeutic agent for allergic diseases selected from amlexanox, tranilast, pemirolast potassium or ketotifen fumarate, an antihistamine, and terpenoids. 2. The ophthalmic composition according to claim 1, wherein the antihistamine is chlorpheniramine maleate or diphenhydramine hydrochloride. 3. The terpenoid contains at least one selected from menthol, camphor, borneol, geraniol, cineol, linalool, eucalyptus oil, bergamot oil, fennel oil and rose oil. Or the ophthalmic composition according to 2.