JPH08175985A - Ophthalmic solution - Google Patents

Abstract

PURPOSE: To obtain ophthalmic solutions especially suitable for instillation in a state of setting a contact lens without stimulus feeling in the instillation by mixing cyclodextrins with an aspartate. CONSTITUTION: (A) At least one kind of aspartate selected from preferably potassium aspartate, magnesium aspartate and sodium aspartate in an amount of usually 0.05-2(wt./vol)% is mixed with (B) at least one kind cyclodextrins selected from preferably α-, β- and γ-cyclodextrin (derivative) in an amount of usually 0.02-0.5(wt./vol)%, in a molar ratio of the components A:B=20:1-1:1 (especially 20:1-10:1 are preferable) to obtain the objective ophthalmic solutions.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an eye drop containing aspartate, and more specifically to an eye drop containing aspartate which does not cause irritation to the eye when applied.

[0002]

BACKGROUND OF THE INVENTION Aspartate is a kind of amino acid existing in the natural world and is known to be involved in the energy production system of the living body.
It is widely used in the field of pharmaceuticals for the purpose of supplementing electrolytes, and also in the field of eye drops, many eye drops are blended with aspartate in anticipation of their tissue activating action or metabolism promoting action.

However, when aspartate is added to eye drops, if the aspartate concentration in the eye drops exceeds a certain level, it causes an unpleasant sensation to the eye when applied. Masking the stimulating sensation with a refreshing agent was essential. Although such masking means can be used for therapeutic eye drops, it is used for eye fatigue, prevention of eye diseases, discomfort when wearing contact lenses, and irritation such as artificial tears. It cannot be used at all for general-purpose eye drops for which a feeling of use without feeling is required.

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an aspartate-containing eye drop without irritation to the eye when applied to the eye without masking with a cooling agent. .

[0005]

Means and Actions for Solving the Problems As a result of intensive studies to achieve the above object, the present inventor has found that the combined use of cyclodextrins with aspartate causes irritation to the eye during application of the eye drops. The present invention has been completed by finding out that there is no.

That is, the present invention provides an eye drop comprising an eye drop containing aspartate and a cyclodextrin compounded therein.

The present invention will be described in more detail below. The eye drop of the present invention contains aspartate and cyclodextrins as essential components. in this case,
As the aspartic acid salt in the present invention, known ones can be used, and examples thereof include potassium aspartate, calcium aspartate, sodium aspartate, and magnesium aspartate, but in particular, potassium aspartate, asparagine. Magnesium acid and sodium aspartate are preferable, and these may be used alone or in combination of two or more.

The amount of the aspartic acid salt in the eye drop of the present invention is not particularly limited, but is usually 0.05 to 2% (weight / volume%, the same applies hereinafter) of the whole eye drop, preferably 0.05. ~ 1.0%, more preferably 0.05
~ 0.6%. If it is less than 0.05%, the tissue activating effect or metabolism promoting effect of aspartate is insufficient, and if it exceeds 2%, the viscosity of the eye drop increases, and as a result, the stickiness around the eyelid increases, and it is used. It may impair the feeling.

On the other hand, examples of the cyclodextrins of the present invention include cyclodextrins and cyclodextrin derivatives having a saccharide cyclic structure of cyclodextrin necessary for inclusion, and examples of cyclodextrins include α
-Cyclodextrin, β-cyclodextrin, γ-
Cyclodextrin and δ-cyclodextrin can be mentioned, and examples of the cyclodextrin derivative include methylated cyclodextrin, hydroxyethylated cyclodextrin, maltosyl-α-cyclodextrin, hydroxyethyl-β-cyclodextrin and triacetyl-. Examples thereof include β-cyclodextrin, and among these, α-cyclodextrin,
β-Cyclodextrin and γ-cyclodextrin are preferably used, and these may be used alone or in combination of two or more.

In the eye drop of the present invention, the aspartic acid salt and the cyclodextrin are mixed in a molar ratio of 20:
The range of 1 to 1: 1 is desirable, but it is preferably 20: 1 to 5: 1, more preferably 20: 1 to 10: 1.
Range. If the blending ratio of cyclodextrins is less than the above range, it may not be possible to sufficiently suppress the irritation sensation to the eye when applied by aspartate, and if it exceeds the above range, aspartate and cyclodextrins. There is a case that the balance of the eye drops and the feeling of use of the eye drop is deteriorated.

The amount of the cyclodextrin compound in the eye drop of the present invention is not particularly limited as long as it is within the range of the above compounding ratio.
It is 0.5%, preferably 0.05 to 0.3%, and more preferably 0.05 to 0.15%. If it is less than 0.02%, the inclusion effect of cyclodextrins may be insufficient, and if it exceeds 0.5%, the viscosity of the eye drop increases, and as a result, the stickiness around the eyelid increases, It may impair the usability.

The use of the eye drop of the present invention is not particularly limited, and it can be used as a therapeutic eye drop or a general eye drop. The eye drop of the present invention is a contact lens, especially a soft contact lens. It is useful as an eye drop for soft contact lenses that can be instilled while wearing. Because contact lenses that use materials with high biocompatibility are foreign substances to the living body, and when wearing contact lenses, the so-called "state where nerves are concentrated in the eye" Become. Therefore, when wearing contact lenses, the sensitivity of the eye to stimuli becomes high,
People who do not wear contact lenses tend to be sensitive to stimuli that cannot be perceived. Therefore, the eye drops such as the eye drop of the present invention which does not cause irritation when applied to the eye drops are particularly suitable as the eye drops to be instilled with the contact lens attached.

In the eye drop of the present invention, in addition to the aspartate salt and the cyclodextrin, various components usually used for preparing an eye drop may be blended in their usual use amounts, if necessary. it can. For example, active ingredients such as anti-inflammatory agents, vitamins, antihistamines and pH
Additives such as regulators, buffers, tonicity agents, stabilizers, solubilizers, preservatives and the like can be added, and eye drops can be prepared by a conventional method.

[0014]

EFFECTS OF THE INVENTION According to the eye drop of the present invention, by incorporating cyclodextrins into an eye drop containing aspartate, irritation to the eye due to the aspartate is suppressed at the time of application to the eye drop, and therefore it is used. It has a good feeling. Therefore, according to the present invention, it is possible to eliminate the sensation of irritating the eye when the eye drops are applied without masking with a cooling agent, and it is possible to expand the blending amount range of aspartate in the preparation of general eye drops.

[0015]

EXAMPLES The present invention will be specifically described below by showing experimental examples and examples, but the present invention is not limited to the following examples.

Experimental Example 1 Potassium aspartate and α
-Dissolved cyclodextrin and sterilized purified water in the amounts shown in Table 1 to make isotonic with sodium chloride,
The sensation of irritation when these isotonic solutions were applied to the eyes of healthy people
It was evaluated by sensory test 1 in which the first name was used as a subject and the following criteria were used for evaluation. The results are also shown in Table 1.

<Evaluation Criteria for Sensory Test 1> O: 8 or more out of 10 subjects do not feel irritation when applied to the eye drop. Δ: 7 to 5 out of 10 test subjects did not feel irritation when applied to the eye drop. ×: 4 or less out of 10 subjects did not feel irritation when applied to the eye drop.

[0018]

[Table 1]

From the results shown in Table 1, the isotonic solution in which potassium aspartate and α-cyclodextrin are used together suppresses the irritation sensation to the eyes when applied to the eye, as compared with the isotonic solution containing potassium aspartate alone. Is recognized.

The same results as in Table 1 were obtained for β-cyclodextrin, γ-cyclodextrin, maltosyl-α-cyclodextrin, hydroxyethyl-β-cyclodextrin and triacetyl-β-cyclodextrin.

[Experimental Example 2] [0021] A solution containing potassium aspartate and α-cyclodextrin in the following composition in the amounts shown in Table 2 was prepared by a conventional method of eye drops, and each solution was fitted with a contact lens. The sensation of stimulation when applied to the eye drop in this state was evaluated by the same method as in Experimental Example 1 above. The results are also shown in Table 2.

There were 10 test subjects in total, of which 5 were soft contact lenses, 3 were oxygen-permeable hard contact lenses, and 2 were hard contact lenses.

<Composition> Taurine 1.0 g Potassium aspartate 0.05 to 2.5 g Sodium chloride 0.3 g α-Cyclodextrin 0 to 0.05 g Boric acid 0.6 g Borax 0.07 g Chloride Benzalkonium 0.01 g Purified water Total 100.0 ml

[0024]

[Table 2]

From the results shown in Table 2, by adding α-cyclodextrin to the eye drop (solution) containing potassium aspartate, the irritation sensation to the eye when the eye drop is applied while the contact lens is worn is suppressed. It is recognized that

Next, eye drops were prepared according to the following formulation by a conventional method to give eye drops according to the examples of the present invention.

Example 1 Sodium chloride 0.7 g Benzalkonium chloride 0.01 g Potassium aspartate 1.0 g α-Cyclodextrin 0.5 g Total amount of purified water 100.0 ml

Example 2 Sodium chloride 0.7 g Benzalkonium chloride 0.005 g Potassium aspartate 0.5 g Magnesium aspartate 0.5 g α-Cyclodextrin 0.1 g Total amount of 100. 0 ml

[Example 3] Taurine 1.0 g Potassium aspartate 0.25 g Sodium chloride 0.3 g α-Cyclodextrin 0.15 g Boric acid 0.6 g Borax 0.07 g Benzalkonium chloride 0.01 g Purified water, total volume 100.0 ml

Example 4 Potassium aspartate 1.0 g Taurine 1.0 g Neostigmine methylsulfate 0.005 g Chlorpheniramine maleate 0.03 g d-α-Tocopherol acetate 0.05 g α-Cyclo Dextrin 0.1 g Boric acid 0.2 g Polyoxyethylene hydrogenated castor oil 60 0.2 g Benzalkonium chloride 0.005 g Total amount with purified water 100.0 ml

Example 5 Potassium aspartate 0.25 g Taurine 1.0 g Epsilon-aminocaproic acid 1.0 g α-Cyclodextrin 0.05 g Boric acid 0.81 g Borax 0.08 g Chlorinated benzal Ruconium 0.05 g Purified water, total 100.0 ml

Example 6 Potassium aspartate 0.05 g Taurine 1.0 g Epsilon-aminocaproic acid 1.0 g β-Cyclodextrin 0.05 g Boric acid 0.81 g Borax 0.08 g Chlorinated benza Ruconium 0.05 g Purified water, total 100.0 ml

Example 7 Potassium aspartate 0.5 g Epsilon-aminocaproic acid 1.0 g γ-Cyclodextrin 0.1 g Boric acid 0.81 g Borax 0.08 g Benzalkonium chloride 0.05 total volume g purified water 100.0 ml

Example 8 Sodium chloride 0.7 g Benzalkonium chloride 0.01 g Potassium aspartate 1.0 g γ-Cyclodextrin 0.1 g Total amount of purified water 100.0 ml

Example 9 Sodium chloride 0.7 g Benzalkonium chloride 0.005 g Potassium aspartate 0.5 g Magnesium aspartate 0.5 g Hydroxyethyl β-cyclodextrin 0.1 g Total amount 100 with purified water 0.0 ml

[Example 10] Potassium aspartate 0.25 g Sodium chloride 0.3 g Hydroxypropyl β-cyclodextrin 0.1 g Boric acid 0.6 g Borax 0.07 g Benzalkonium chloride 0.05 total volume g purified water 100.0 ml

Example 11 Potassium aspartate 1.0 g Taurine 1.0 g Neostigmine methylsulfate 0.005 g Chlorpheniramine maleate 0.03 g d-α-tocopherol acetate 0.05 g Triacetyl β -Cyclodextrin 0.1 g Boric acid 0.2 g Polyoxyethylene hydrogenated castor oil 60 0.2 g Chlorobutanol 0.2 g Benzalkonium chloride 0.005 g Total amount with purified water 100.0 ml

Example 12 Potassium aspartate 0.25 g Taurine 1.0 g Epsilon-aminocaproic acid 1.0 g Maltosyl α-cyclodextrin 0.5 g Boric acid 0.81 g Borax 0.08 g Chloride Benzalkonium 0.05 g Total amount of purified water 100.0 ml

Example 13 Potassium aspartate 0.5 g Taurine 0.5 g Epsilon-aminocaproic acid 1.0 g β-Cyclodextrin 0.5 g Boric acid 0.9 g Borax 0.09 g Chlorinated benza Ruconium 0.05 g Purified water, total 100.0 ml

Example 14 Potassium aspartate 0.5 g Epsilon-aminocaproic acid 1.0 g γ-Cyclodextrin 0.5 g Boric acid 0.81 g Borax 0.08 g Benzalkonium chloride 0.05 total volume g purified water 100.0 ml

Example 15 Potassium aspartate 2.0 g Pyridoxine hydrochloride 0.1 g γ-Cyclodextrin 0.5 g Boric acid 0.5 g Borax 0.04 g Benzalkonium chloride 0.05 g Purification 100.0 ml with water

The irritation sensation when the eye drops of each Example were applied was evaluated by a sensory test 2 in which 10 healthy men were used as subjects and evaluated according to the following criteria. The results are shown in Table 3.

<Evaluation Criteria for Sensory Test 2> O: No irritation is felt when applied to the eye drop. Δ: A slight irritation is felt when applied to the eye drop. X: Irritation is felt when applied to the eye drop.

[0044]

[Table 3]

From the results shown in Table 3, it is recognized that the eye drop of the present invention has almost no irritation to the eye when applied, even if the eye drop contains 0.25 to 1% of aspartate.

Claims (5)

[Claims] 1. An eye drop comprising an aspartate-containing eye drop and a cyclodextrin compounded therein. 2. The eye drop according to claim 1, wherein the mixing ratio of the aspartic acid salt and the cyclodextrin is 20: 1 to 1: 1 in terms of molar ratio. 3. The eye drop preparation according to claim 1, wherein the aspartate is one or more selected from potassium aspartate, magnesium aspartate and sodium aspartate. 4. The eye drop preparation according to claim 1, 2 or 3, wherein the cyclodextrins are one or more selected from α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin and derivatives thereof. 5. An eye drop for a contact lens, which can be instilled with the contact lens attached.
The eye drop preparation according to any one of 1.