JP2003055220A - Ibudilast-containing ophthalmic composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an ophthalmic composition effective against congestion symptom of the ocular-mucous membrance. SOLUTION: This ophthalmic composition is obtained by formulating (a) ibudilast, and (b) at least one kind selected from the group consisting of tetrahydrozoline, naphazoline, phenylephrine ephedrine, methylephedrine, epinephrine and a salt thereof. The eye drop or the eye ointment comprises the ophthalmic composition.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an ophthalmic composition, and more particularly to an ophthalmic composition containing ibudilast, which is effective in reducing / eliminating hyperemic symptoms of ocular mucosa.

[0002]

2. Description of the Related Art Diseases showing hyperemia of the eye mucous membrane, such as conjunctivitis, are inflammatory diseases of the eye mucous membrane. The causes of conjunctivitis are diverse, and in the past, the symptoms were mainly based on bacterial infection, but in recent years, allergies have also attracted attention as a major etiological factor.

Generally, allergens are considered to be the most effective causal therapy for allergies, and hyposensitization therapy is also used, but the frequency of visits to the hospital is relatively high,
Since the treatment is for a long period of time, the time, financial, and psychological burden on the patient is large, and the reality is that it is not easily established as a treatment method. Therefore, treatment of such diseases must be performed by momentum symptomatic treatment.

Particularly in the treatment of conjunctivitis etc., it is important in terms of treatment how quickly various symptoms such as hyperemia of the ocular mucous membrane are reduced and eliminated. Among them, the hyperemic symptoms such as swelling of the ocular mucosa are QOL ( From the viewpoint of (Quality of Life) and from the viewpoint of preventing the transition to serious symptoms, it is required to improve at an early stage. Doing is important.

However, the symptomatic treatment as described above does not provide a sufficient therapeutic effect and the action is transient, so that the number of times of administration is inevitably increased. Therefore, it has been urgently desired to develop an eye drop or an eye ointment that exhibits a sufficient therapeutic effect that conventional symptomatic drugs do not have.

[0006]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an ophthalmic composition which is effective in reducing / eliminating the hyperemic condition of the ocular mucosa.

[0007]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that a composition in which ibudilast, which is an antiallergic drug, and tetrahydrozoline, which is a vasoconstrictor, are combined as active ingredients. It was found that the substance exhibits an extremely excellent effect in reducing / eliminating various symptoms due to hyperemia of the eye mucosa, and completed the present invention.

That is, the present invention provides (a) ibudilast,
And (b) at least one selected from the group consisting of tetrahydrozoline, naphazoline, phenylephrine, ephedrine, methylephedrine, epinephrine, and salts thereof, which is an ophthalmic composition.

Ibudilast in the present invention is an antiallergic drug and is used for the treatment of bronchial asthma and the like.

In the present invention, tetrahydrozoline, naphazoline, phenylephrine, ephedrine, methylephedrine and epinephrine are vasoconstrictors, and they may be salts. Examples of the salt include mainly hydrochlorides and nitrates. Not only one kind of tetrahydrozoline and the like may be used, but two or more kinds may be used in combination.

The blending amount of each active ingredient with respect to the entire ophthalmic composition of the present invention is as follows. Ibzilast is 0.001
˜0.015 mass%, preferably 0.002˜0.01 mass%. This is because if it is less than 0.001% by mass, the action of reducing / eliminating hyperemia of the ocular mucosa does not sufficiently appear, and if it exceeds 0.015% by weight, irritation or damage to the ocular mucosa may occur.

On the other hand, the content of tetrahydrozoline, naphazoline, phenylephrine, ephedrine, methylephedrine, epinephrine or their salts is 0.0005 to 1.25% by mass, preferably 0.001 to 1% by mass. this is
If it is less than 0.001% by mass, the effect of reducing / eliminating hyperemia of the eye mucosa cannot be sufficiently obtained, and if it exceeds 1% by mass, a resistance effect may occur, which is not preferable.

The blending amount of each component (b) is usually 0.03 to 1250 parts by mass, preferably 0.1 to 500 parts by mass, relative to 1 part by mass of ibudilast.

The ophthalmic composition of the present invention may contain other components, if necessary, in addition to the above components.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION The ophthalmic composition of the present invention can be prepared by a conventional method by incorporating ibudilast, tetrahydrozoline and the like as active ingredients.

A pharmaceutical carrier is added to the ophthalmic composition of the present invention, and other active ingredients are also added, if necessary, to prepare and provide various dosage forms such as eye drops. be able to. Examples of the carrier for the preparation include various excipients, binders, lubricants, surfactants, solubilizers, buffers, preservatives, dyes and preservatives.

The ophthalmic composition of the present invention is usually provided as an eye drop or an eye ointment. When used as an eye drop, 1 to several drops are applied at a time, and when used as an eye ointment, an appropriate amount is applied to an eye drop stick and applied to the inside of the lower eyelid.

[0018]

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

(Example 1) Ibudilast 10 mg Naphazoline hydrochloride 2 mg The above components were weighed and uniformly mixed, and then purified water 100 was added.
It was dissolved in mL and an appropriate amount was dispensed into a sterilized eye drop container to prepare an eye drop.

(Example 2) Ibudilast 10 mg dl-methylephedrine hydrochloride 75 mg The above components were weighed and mixed uniformly, and then an eye drop was prepared according to Example 1.

(Example 3) Ibudilast 10 mg Tetrahydrozoline hydrochloride 50 mg The above components were weighed and uniformly mixed, and then an eye drop was prepared according to Example 1.

Example 4 Ibudilast 10 mg Epinephrine Hydrochloride 3 mg The above components were weighed and uniformly mixed, and then an eye drop was prepared according to Example 1.

Example 5 Ibudilast 10 mg Phenylephrine hydrochloride 100 mg The above components were weighed and mixed uniformly, and then an eye drop was prepared according to Example 1.

(Example 6) Ibudilast 10 mg Naphazoline hydrochloride 3 mg Propylene glycol 500 mg Methyl paraoxybenzoate 30 mg The above components were weighed and uniformly mixed, and then dissolved in 100 g of ointment base (liquid paraffin + low polymerization polyethylene). Then, it was filled in a sterilized tube to prepare an eye ointment.

(Test Example 1) [Relaxation effect of the combined preparation on the hyperemic reaction of rabbit eye mucous membrane] Three 12-week-old Japanese white male rabbits were used in each group, and 3.
1 mL of 0% capsaicin solution was instilled to induce a hyperemic reaction of the ocular mucosa, and 1 mL of each drug was instilled according to the prescription (in 100 mL) shown in Table 1 to compare the decongestant removal effect at 1 hour after instillation. .

As an evaluation method, 5 points; very hyperemic, 4 points; fairly hyperemic, 3 points; clearly hyperemic, 2 points; slightly hyperemic, 1 point; hyperemic However, it was very weak, 0 point; almost no hyperemia, and a 6-level evaluation was performed, and the average value among 3 animals was compared. The results are shown in the lower column of Table 1 as the degree of hyperemia reaction.

[0027]

[Table 1]

[Table 1]

As is clear from Table 1, the relieving action on the ocular mucosal hyperemic reaction was remarkably superior to the other control groups in the groups A to B, and the eye drops of the present invention contained ibudilast and each vasoconstrictor alone. In comparison with the case of the above-mentioned use, a remarkable effect was obtained in the action of reducing / eliminating ocular mucosal hyperemia.

[0029]

INDUSTRIAL APPLICABILITY According to the present invention, it has become possible to provide an ophthalmic composition which is extremely effective in reducing / eliminating the hyperemia of the ocular mucosa.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 31/4164 A61K 31/4164 A61P 27/14 A61P 27/14 43/00 121 43/00 121 (72) Inventor Joji Nakagami 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. (72) Inventor Katsuyoshi Aikawa 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical F-term ( Reference) 4C076 AA06 AA12 BB24 CC05 CC10 DD37 FF12 4C086 AA01 AA02 BC38 CB05 MA02 MA04 MA17 MA28 NA14 ZA33 ZB11 ZB13 4C206 FA10 FA14 MA02 MA04 MA37 MA48 MA78 NA14 ZA33 ZB11 ZB13

Claims (2)

[Claims] 1. An ophthalmic composition comprising (a) ibudilast and (b) at least one selected from the group consisting of tetrahydrozoline, naphazoline, phenylephrine, ephedrine, methylephedrine, epinephrine and salts thereof. Composition. 2. The ophthalmic composition according to claim 1, which is an eye drop or an eye ointment.