JPH0119362B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to anti-inflammatory eye drops characterized by containing a non-steroidal anti-inflammatory agent as a main ingredient and a calcium salt or magnesium salt as an eye irritation alleviating agent. Ocular inflammation is caused by trauma, allergens, or infection, and steroid eye drops are currently the mainstay of treatment. However, there are concerns that steroid eye drops may induce serious side effects such as exacerbation of infections caused by bacteria, viruses, etc. and the occurrence of steroid glaucoma, and there are problems with their continued use, so we are developing steroids with fewer side effects. The introduction of non-steroidal anti-inflammatory agents into the ophthalmic field is eagerly awaited. The main reason why it has been difficult to commercialize eye drops containing non-steroidal anti-inflammatory drugs as the main drug is that these compounds almost universally irritate the mucous membranes and eyes, causing intense eye pain. The present inventors have conducted various studies on methods for alleviating this eye irritation and eye pain, and have completed the present invention. That is, the present invention provides an eye irritation alleviating agent containing a non-steroidal anti-inflammatory agent selected from ibuprofen, indomethacin, ketoprofen, naproxen and flufenamic acid as a main ingredient, and a salt of calcium or magnesium with a physiologically acceptable acid. An anti-inflammatory eye drop characterized by containing:
It is related to. 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 using a conventional aqueous formulation using the above-mentioned active ingredient and eye irritation additive. The standard drug formulation will be explained below. The concentration of the active ingredient is usually 0.01 to 0.1% as standard, and is adjusted as appropriate depending on the purpose of use. PH is preferably 7-8. As the buffer, 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. Suitable solubilizing agents include polyoxyethylene sorbitan monooleate (trade name: Tween 80), polyoxyethylene oxystearic acid triglyceride, polyethylene glycol, and α- or β-cyclodextrin (hereinafter abbreviated as α- or β-CD). It is. Polyvinylpyrrolidone, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, etc. can also be added as a thickener. As an eye preservative, bersalkonium chloride, cetylpyridinium chloride, chlorobutanol, tyromesal, etc. can also be added. Calcium salts or magnesium salts used as eye irritation relievers are usually 0.3 to 2 per mole of the active drug.
It is added in a molar ratio, preferably 1 to 1.5 molar. Specific examples of pharmaceutical formulations are shown below. Prescription example 1 Naproxen 100mg, borax 573mg, boric acid 868mg
mg, NaCl290mg and β-CD1000mg in distilled water
Dissolve in 80ml and add 150mg of magnesium chloride to this solution.
Add and dissolve, dilute with distilled water, make 100 ml, sterilize and filter, and use as eye drops. Prescription example 2 Ketoprofen 100mg, Borax 573mg, Boric acid
Dissolve 868mg, 290mg of NaCl, and 100mg of tween-80 in approximately 80ml of distilled water, add and dissolve 150mg of calcium pantothenate, and dilute with distilled water.
Dilute to 100ml, filter to sterilize, and use as eye drops. Next, the fact that eye irritation of the eye drops of the present invention is significantly reduced will be explained using test examples. Test example (rabbit eyeblink reaction test) For the five non-steroidal active compounds shown in Table 1, the controls, comparisons, (A), and (A) shown in Table 2 were tested.
Eye drops with six different formulations (B), (C), and (D) were prepared and used as test solutions. Test solution 1 at approximately 30°C in one eye of a domestic rabbit in a fixed container.
A drop (approximately 0.05 ml) was instilled into the eye, and the number of blinks was measured for 1 minute immediately after instillation to evaluate the irritation-reducing effect. [See Fukui, Ikemoto; Modern Clinical Practice 4 , (7) 227 (1970)]

【table】

[Table] 〓
The results of this test are shown in Table 3.

[Table] As is clear from the results in Table 3, the formulation of the present invention
For eye drops prepared by (A), (B), (C), and (D), the number of blinks was significantly lower than that of the (comparative) formulation that did not contain calcium salts or magnesium salts, regardless of the active ingredient. The concentration decreased significantly, and there was almost no difference between the formulation solution containing only a PH buffer and an isotonizing agent (control).

Claims (1)

[Claims] 1 Containing a non-steroidal anti-inflammatory agent selected from ibuprofen, indomethacin, ketoprofen, naproxen and flufenamic acid as the main drug, and containing a salt of calcium or magnesium and a physiologically acceptable acid as an eye irritation alleviating agent. Anti-inflammatory eye drops.