JPS58174309A - Antiphlogistic eye drop - Google Patents

Abstract

PURPOSE:To provide an antiphlogistic eye drop giving reduced irritation and sore to the eye on application, by using a non-steroidal antiphlogistic agent containing carboxyl group in the molecular structure, as a main drug component, and adding a physiologically permissible Ca salt or Mg salt as an irritation mitigating agent. CONSTITUTION:A non-steroidal antiphlogistic agent containing carboxyl group (e.g. ibuprofen, indomethacin, diclofenac sodium, etc.) is used as a main drug component, and added with a Ca salt or a Mg salt of a physiologically permissible acid (e.g. calcium lactate, calcium pantothenate, etc.) as an irritation mitigating agent, to obtain the objective antiphlogistic eye drop. The concentration of the main drug component in the drop is normally 0.01-0.1%, and the amount of the irritation mitigating agent is 1-1.5mol per 1mol of the main drug component. The eye drop may further contain a buffer solution (e.g. phosphate) to keep the pH at 7-8, an isotonic agent, a dissolution assistant, an antiseptic agent, etc.

Description

[Detailed description of the invention] The present invention uses a non-steroidal anti-inflammatory drug as a crude drug.

The present invention relates to an anti-inflammatory eye drop containing calcium salt or magnesium salt as an eye irritation alleviating agent.

Ocular inflammation is caused by trauma, allergens, or infection, and the current mainstream treatment for this is nuteroid eye drops.

However, there are concerns that steroid eye drops may induce serious side effects, such as exacerbation of infections caused by viruses and the occurrence of steroid-related complications.

Because of their long-term use, the development of steroids with fewer side effects and the introduction of non-steroidal anti-inflammatory drugs into the ophthalmology field are eagerly awaited.

A major reason why eye drops based on non-steroidal anti-inflammatory drugs have not been put into practical use is that these compounds almost universally irritate the mucous membranes and eyes and cause intense eye pain, so they cannot be instilled into the eyes. by.

The present inventors conducted various studies on methods for alleviating this eye irritation and eye pain and completed two inventions.

That is, 1 the present invention [contains a non-steroidal anti-inflammatory agent containing a carboxy group in its molecular structure as a crude drug, and also contains a salt of calcium or magnesium and a physiologically acceptable acid as an eye irritation alleviating agent] Anti-inflammatory eye drops featuring:

”.

Representative examples of non-steroidal anti-inflammatory agents containing a carboxyl group in the molecular structure used as the crude drug of the present invention include ibuprofen, indomethacin, ketoprofen, diclofenac sodium, naproxen, flufenamic acid, and the like.

In the present invention, the calcium salt and magnesium salt used as the eye irritation alleviating agent may be any salt with a physiologically acceptable acid.

Typical examples include calcium salts such as calcium lactate, calcium pantothenate, calcium acetate, calcium chloride, calcium propionate, and calcium gluconate, and magnesium salts such as magnesium sulfate, magnesium lactate, and magnesium chloride.

The eye drops of the present invention can be formulated into a conventional aqueous formulation using the above-mentioned active ingredient and eye irritation alleviating agent.

The standard drug formulation will be explained below.

The concentration of the crude drug is usually 0.01 to 0.1-0, and is adjusted as appropriate depending on the purpose of use.

The pH is preferably 7-8. As hook loosening agents, phosphates,
Boric acid, borax, organic acids, etc. can be used as appropriate.

The osmotic pressure ratio is preferably 1. As the tonicity agent, sodium chloride, mannitol, etc. can be used.

Examples of solubilizing agents include polyoxyethylene sorbitan monooleate (trade name: Tween 80) #polyoxyethylene oxine stearate triglyceride, polyethylene glycol, α- or β-cyclodextrin (hereinafter abbreviated as α- or β-CD). ) is appropriate. Polyhinylpyrrolidone, methylcellulose as thickeners,
Hydroxypropylmethylcellulose, hydroxypropylcellulose, etc. can also be added.

As an ophthalmic preservative, benzalkonium chloride, cetylpyridinium chloride, chlorbutanol, telomesal, etc. can also be added. .

The calcium salt or magnesium salt used as a limiting irritation reliever is usually added at a ratio of 0.3 to 2 mol, preferably 1 to 1.5 mol, per 1 mol of the crude drug.

Specific examples of pharmaceutical formulations are shown below.

Prescription example 1゜Diclofenac sodium 10011v, Hokusan 57
3m9. Boric acid 868 Q, Na C129089
and β-CD1000 is dissolved in about 80 μl of distilled water, 150 μg of calcium lactate is added to this solution, dissolved, diluted with distilled water, sterilized and filtered with 100 μl to prepare eye drops.

Prescription example 2゜diclofenac sodium 10011. NaHPO
2 (Anhydrous) 20019. Na, HPO4 (anhydrous) 7
10 #, 300 μg of Mg, β-CD 1000 μm was dissolved in about 80 μg of water, 150 μg of calcium pantothenate was added to this solution, dissolved, and diluted with distilled water to give a solution of 10 μg.
0 - Binding.

Filter to sterilize and use as eye drops.

Next, the fact that the eye irritation of the eye drops of the present invention is reduced due to wear and tear will be explained using Test Example a.

Test Example (Rabbit Blink Response Test) For the six non-steroidal active compounds shown in Table 1, the controls, comparisons, and prisoners are shown in Table 2, respectively.

Eye drops with six different formulations (C), (Q, and (L)i) were prepared and used as test solutions.

One drop (approximately 0.05 m) of the test solution at about 30°C was instilled into one eye of a domestic rabbit placed in a fixed container, and the number of blinks for 1 minute immediately after the second instillation was measured to evaluate the irritation-reducing effect.

[Fukui, Ikemoto; Modern clinical soil, (7) 227 (19
70)] Table 1 (Main drug compound) Table 2 (Prescription of test solution) The results of this test are shown in Table 3.

Table 3 (Rabbit blink test results) As is clear from the results in Table 3, 9 formulations of the present invention (A)
, (B), l? ) and 0, the number of blinks was significantly reduced compared to the (comparative) formulation that did not contain calcium salts or magnesium salts, regardless of the active ingredient, and the pH::): moderate. agent and tonicity agent only (control)
Almost no difference was observed from the prescription liquid.

Patent applicant: Wakamoto Pharmaceutical Co., Ltd.

Claims (1)

[Claims] Anti-inflammatory eye drops containing a nonsteroidal anti-inflammatory agent containing a carboxyl group in its molecular structure as a crude drug, and a salt of calcium or magnesium and a physiologically acceptable acid as an eye irritation alleviating agent. .