JP2002265357A - Composition for use in ophthalmology - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition which is useful for uses in ophthalmology, has excellent stability and excellent antiseptic force, and is not irritative. SOLUTION: This composition for uses in ophthalmology is characterized by comprising (A) panthenol, (B) boric acid and/or its salt, and (C) a compound having three or more hydroxyl groups in the molecule (excluding the panthenol).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an ophthalmic composition having excellent stability and preservative power and having no irritation.

[0002]

2. Description of the Related Art Pantothenic acids (including the precursor panthenol in the present invention) are a kind of vitamin that functions as coenzyme A in a living body, and are essential for the normal function of eye cells. Is indispensable.
However, because of its low stability in aqueous solution, it has been a technical problem in formulating it as eye drops.

As a technique for improving the stability of pantothenic acids in an aqueous solution, Japanese Patent Application Laid-Open No. 05-17355 discloses a stable eye drop prepared by mixing a specific amount of boric acid in an aqueous solution containing pyridoxine hydrochloride and pantothenic acids. Have been. However, the amount of boric acid used in this composition is limited to a small amount of 300% or less with respect to pantothenic acids, and if it exceeds this amount, the stability decreases. This is because, when boric acid is present in excess, pantothenic acids and boric acid form a complex compound, so that the stability of pantothenic acids is impaired.

[0004] On the other hand, since ophthalmic compositions are aqueous preparations, preservatives are generally added to the preparations to impart preservative power against secondary contamination and the like. Particularly, in a composition containing an oil component such as pantothenic acids, maintaining the preservative power is an important issue. However, when applied to contact lens wearers and dry eye patients, preservatives may be irritating. Therefore, there has been a demand for eye drops that can suppress eye irritation due to a preservative and maintain the preservative power.

[0005]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide an ophthalmic composition containing pantothenic acids, having excellent antiseptic properties, low irritation and excellent stability.

[0006]

Means for Solving the Problems The present inventors have conducted intensive studies to achieve the above object, and as a result, have found that pantothenic acids, in particular, pantenol, which is a precursor among them, boric acid (salt), By blending a compound having three or more hydroxyl groups in the molecule, it has been found that the stability and preservative power of the above-mentioned components are remarkably increased, and that an ophthalmic composition with suppressed eye irritation can be obtained. It was completed. It should be noted that panthenol is a precursor (precursor) that is converted into pantothenic acid in a living body to exert its effect on a living body (ocular cells) after use of the ophthalmic composition.

That is, the present invention relates to (A) panthenol,
(B) boric acid and / or a salt thereof, (C) 3 per molecule
An ophthalmic composition containing a compound having at least two hydroxyl groups (excluding panthenol) is provided.

[0008] The ophthalmic composition of the present invention is particularly suitable as an ophthalmic composition for dry eye patients and contact lens wearers who are susceptible to irritation of preservatives due to reduced tears and eye disorders. It is.

BEST MODE FOR CARRYING OUT THE INVENTION

The panthenol of the component (A) in the present invention includes panthenol and its derivatives which can be used for ophthalmology. Specific examples include panthenol, pantethine, pantetheine pantothenyl alcohol, and pantothenyl ethyl ether. Among the above, panthenol (for example, Panthenol manufactured by Fuji Pharmaceutical Co., Ltd.) is particularly preferred in terms of stability, and may contain pantothenic acid as long as the stability is not impaired.

The content of the component (A) in the present invention is preferably from 0.001 to 20 g / 10 based on the whole composition.
0 mL, more preferably 0.01 to 10 g / 10
0 mL. By setting the concentration in this range, a particularly stable aqueous liquid can be obtained.

In the present invention, boric acid and / or component (B) are used.
Examples of the salt include boric acid, borax, sodium tetraborate decahydrate, and salts thereof. These boric acids can be used alone or in appropriate combination of two or more kinds.

The component (B) in the present invention accounts for more than 300% of panthenol, and 0.1% in the composition.
001 to 10 g / 100 mL are preferred. More preferably, the amount in the composition is preferably 0.01 to 5 g / 100 mL. When the concentration is within the above range, the composition of the present invention can provide an ophthalmic composition having excellent panthenol stability and eye irritation and good antiseptic power.

In the present invention, the polyhydric alcohols having three or more hydroxyl groups of the component (C) include glucose,
Sugars such as glucose and derivatives thereof, sugar alcohols such as glycerin, mannitol and sorbitol and derivatives thereof, cyclodextrins such as α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin and derivatives thereof But are not limited to these. In the case of the present invention, among these, glycerin, mannitol, glucose and α-cyclodextrin are particularly preferred. These polyhydric alcohols can be used alone or in combination of two or more.

In the present invention, the compounding amount of the above components is 0.1.
001 to 20 g / 100 mL, preferably 0.0
It is 1 to 10 g / 100 mL. By setting the concentration within this range, the effects aimed by the present invention can be obtained. Also,
The compounding ratio (weight ratio) to the boric acid as the component (B) is (C) / (B) = 0.01 to 2000,
More preferably, it is preferable to mix it in a range of 0.02 to 1000 from the viewpoint of increasing the stability of the first component, panthenol.

The ophthalmic composition of the present invention can further improve the stability of panthenol by adjusting the pH to 4.0 to 7.0. Furthermore, it is preferable from the viewpoint of eye irritation. The pH can be adjusted using an alkaline agent such as sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, sodium citrate, or an acid such as hydrochloric acid, citric acid, phosphoric acid, or acetic acid. Further, the composition preferably contains a buffering agent such as epsilon-aminocaproic acid, L-glutamic acid, sodium L-glutamate, tromethamine, and the like, and the compounding amount is preferably 0.0001 to 10 g / mL, and particularly preferably 0.1 to 10 g / mL.
It is preferably 001 to 5 g / 100 mL.

The composition of the present invention preferably contains a preservative in addition to the above components. As preservatives, sorbic acid, potassium sorbate, chlorhexidine gluconate, benzalkonium chloride, benzethonium chloride, alkyl polyaminoethyl glycine (for example, Tego-51,
KOTOBUKI CO. LTD), but is not limited thereto.

In the present invention, the content of the preservative is as follows:
It is 0.0001 to 1 g / 100 mL, preferably 0.0005 to 0.03 g / 100 mL. By controlling the concentration within this range, the ophthalmic composition of the present invention can be obtained in which eye irritation is particularly suppressed and the antiseptic power is good.

The ophthalmic composition of the present invention may contain, in addition to the above-mentioned components, if necessary, various components usually used for preparing ophthalmic compositions such as eye drops in the usual amounts. Can be. Specific examples are shown below, but the present invention is not limited to these examples.

(D) Active ingredient (drug) Anti-inflammatory agent such as dipotassium glycyrrhizinate, allantoin, berberine chloride, berberine sulfate, sodium azulene sulfonate, zinc sulfate, zinc lactate, lysozyme chloride, flavin adenine dinucleotide sodium (Active vitamin B2), pyridoxine hydrochloride (vitamin B
6), vitamins such as cyanocobalamin (vitamin B12), vitamin E acetate, calcium pantothenate, sodium pantothenate, retinol acetate, retinol palmitate (vitamin A palmitate), epinephrine, epinephrine hydrochloride, Decongestant components such as ephedrine hydrochloride, naphazoline hydrochloride, naphazoline nitrate, phenylephrine hydrochloride, tetrahydrozoline hydrochloride, antihistamines such as diphenhydramine hydrochloride, chlorpheniramine maleate, sulfamethoxazole, sulfamethoxazole sodium, sulfisoxazole , Sulfo agents such as sodium sulfisomidine, antiallergic agents such as cromoglycic acid, sodium cromoglycate, tranilast and potassium pemirolast, local anesthetics such as chlorobutanol, LA Amino acids such as potassium paraginate, magnesium L-aspartate, potassium magnesium L-aspartate (equivalent mixture), aminoethylsulfonic acid (taurine), chondroitin sulfate sodium, epsilon aminocaproic acid, L-glutamic acid, sodium L-glutamate Active ingredients such as neostigmine methyl sulfate, inorganic salts such as sodium chloride, potassium chloride, calcium chloride, sodium bicarbonate, sodium carbonate, dried sodium carbonate, magnesium sulfate, etc.

(E) Stabilizers Ethylenediaminetetraacetic acid, disodium ethylenediaminetetraacetate (sodium edetate), etc.

(F) Solubilizers Antioxidants such as dibutylhydroxytoluene (BHT) and ascorbic acid, ethylene glycol, propylene glycol, and polyoxyethylene hydrogenated castor oil 60 (for example, HCO-60, Nippon Gas Co., Ltd.) Factorant Industrial Co., Ltd.)
Polyoxyethylene (20) sorbitan monooleate (for example, TO-10, Nippon Surfactant Industry Co., Ltd.)
Polyoxyethylene polyoxypropylene block copolymer (for example, Poloxama-407, manufactured by NOF Corporation)

(G) Fragrance (cooling agent) Menthol, camphor, borneol, geraniol,
Linalool, cineole, cool mint, peppermint water, peppermint oil, fennel oil, bergamot oil, eucalyptus oil, etc.

(H) Thickener Methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, carboxymethylcellulose, polyvinyl Alcohol, polyvinylpyrrolidone, hyaluronic acid, sodium hyaluronate, etc.

(I) Buffer Phosphoric acid, sodium phosphate, citric acid, sodium citrate, sodium carbonate, sodium hydrogen carbonate, tromethamine, etc.

The ophthalmic composition such as eye drops and eyewash of the present invention can be prepared by a conventional method.

The use of the ophthalmic composition of the present invention is not particularly limited, and it can be used as eye drops, eyewash, and contact lens mounting solution. Especially effective for dry eye patients and eye fatigue when wearing contact lenses, eye drops for dry eye or hard contact lenses, oxygen permeable hard contact lenses, soft contact lenses, frequent replacement The present invention is useful as an eye drop for contact or a contact lens mounting solution that can be instilled in a state of wearing a soft contact lens of a type or a replaceable soft contact lens every day. Also, it can be used as a single-use eye drop containing no preservative.

[0027]

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

(Preparation of Ophthalmic Composition of Example 1) Panthenol 0.05 g, boric acid 1.0 g, glycerin 1.0
g, sodium hydrogencarbonate 0.05 g, sodium chloride 0.5 g, benzalkonium chloride solution (10%) 0.03
g was dissolved in purified water, and the pH was adjusted to 5.0 by adding an appropriate amount of hydrochloric acid. The total amount was adjusted to 100 mL, and the mixture was filtered to prepare eye drops. Other compositions in the table were prepared according to Example 1.

<Evaluation of Stability of Panthenol> After the test solution was sealed in a glass ampule, severe storage was performed at 70 ° C. for one week. For the liquid after storage, the amount of panthenol was quantified by HPLC, and the remaining ratio of panthenol was evaluated by the following formula.

Panthenol residual ratio (%) = (amount of panthenol after storage / amount of panthenol before storage) × 100

The evaluation criteria in the table are as follows. ◎: Residual rate is 98% or more ：: Residual rate is 90% or more and less than 98% Δ: Residual rate is 80% or more and less than 90% ×: Residual rate is less than 80%

<Eye irritation test> Evaluation of eye irritation was carried out in accordance with the short-term test method for ocular mucosal irritation test of an ophthalmic preservative in the Ministry of Health and Welfare Scientific Research Report (1970). ：: Average score by Draize method is 0 or more and less than 2 points △: 2 or more and less than 5 points ×: 5 or more points

<Antiseptic test> The test was performed according to the preservative test (eye drops) described in the 13th revised edition of the Japanese Pharmacopoeia. ：: Applicable to all 5 strains ×: Not applicable

[0034]

[Table 1]

[0035]

[Table 2]

[0036]

[Table 3]

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (Reference) A61K 47/40 A61K 47/40 A61P 27/04 A61P 27/04

Claims (6)

[Claims] 1. A composition comprising (A) panthenol, (B) boric acid and / or a salt thereof, and (C) a compound having three or more hydroxyl groups in one molecule (excluding panthenol). A characteristic ophthalmic composition. 2. Boric acid and / or a salt thereof, wherein (A) panthenol, (B) more than 300% of panthenol and the content in the composition is 0.001 to 10 g / 100 ml, C) An ophthalmic composition comprising a compound having three or more hydroxyl groups in one molecule (excluding panthenol). 3. The compound according to claim 1, wherein the compound having three or more hydroxyl groups is one or more selected from glycerin, mannitol, glucose and α-cyclodextrin. Ophthalmic composition. 4. The ophthalmic composition according to claim 1, further comprising a preservative. 5. The ophthalmic composition according to claim 1, which is an ophthalmic composition for a contact lens wearer. 6. The ophthalmic composition according to claim 1, which is an ophthalmic composition for dry eye patients.