JP2012006962A - Ophthalmic composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an ophthalmic composition improving stability of a tear film.SOLUTION: The ophthalmic composition containing 0.1-5w/v% of trometamol and 0.001-0.3 w/v% of tocopherol acetate remarkably improves the stability of the tear film, thus suppressing drying of a tear fluid, and is especially useful as the ophthalmic composition for preventing and treating dry eye.

Description

  The present invention relates to an ophthalmic composition, and more particularly to an ophthalmic composition useful for improving tear film stability.

  In recent years, due to various environmental changes such as indoor drying due to the widespread use of air conditioners and the increase in VDT work for personal computers and the like, there are increasing opportunities to place a burden on the eyes. In particular, many cases complain of dry eye symptoms such as dry eyes and tired eyes, and dry eyes also cause symptoms such as conjunctival hyperemia, pruritus, foreign body sensation and discomfort. As a treatment for such dry eye, a method using an artificial tear is mainly used in order to prevent dryness of the eye. In addition, for treatment of hyperemia and pruritus, an eye drop containing a decongestant or an antihistamine can be used if dry eye symptoms are mild.

  However, these treatments can temporarily improve the symptoms, but if VDT work is performed again, the eyes will dry in a short period of time and cause hyperemia, which is not satisfactory. There wasn't.

  Recently, vitamin As such as retinol palmitate have been found to be effective against dry eye symptoms (Ohashi, Ikkaku. 41, 368 (1987)), but are still established as therapeutic agents. Not.

  Accordingly, there has been a demand for the development of a technique for treating dry eye by more stably holding the tear film and suppressing the drying of the tear.

  The present invention has been made in view of the above circumstances, and an object thereof is to provide an ophthalmic composition that improves the stability of a tear film.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors, as shown in the examples described later, by using a specific organic amine such as trometamol together with fat-soluble vitamins, It was found that the stability of the tear film was remarkably improved as compared with the case where vitamins were used alone or in combination with other compounds, and the present invention was completed.

  That is, the present invention is an ophthalmic product characterized by containing one or more organic amines and fat-soluble vitamins selected from the group consisting of amino alcohols, piperazines, diamine sulfonates, and derivatives thereof. A composition is provided. Here, it is more preferable that the organic amine is trometamol. Moreover, if the said fat-soluble vitamins are vitamin A, it is more suitable.

  According to the ophthalmic composition of the present invention, an ophthalmic composition that significantly improves the stability of the tear film can be obtained. Therefore, the ophthalmic composition of the present invention can suppress the drying of tears, and is particularly useful as an ophthalmic composition for preventing and treating dry eye.

  Hereinafter, the present invention will be described in more detail. As described above, the ophthalmic composition of the present invention comprises at least one organic amine selected from amino alcohols and derivatives thereof, piperazine and derivatives thereof, sulfonated diamines and derivatives thereof, and fat-soluble vitamins. It contains. Here, the above-mentioned amino alcohols, piperazines, diamines sulfonated products and derivatives thereof to be blended in the ophthalmic composition of the present invention are particularly those types that can be blended in the ophthalmic composition. For example, amino alcohols such as trometamol, monoethanolamine, diethanolamine, triethanolamine, 4- (2-hydroxyethyl) -1- (2-sulfoethyl) piperazine (HEPES), 1,4- Sulfoalkylpiperazines such as bis (2-sulfoethyl) piperazine (PIPES), 1,4-bis (3-sulfopropyl) piperazine (PIPPS), 1,4-bis (4-sulfobutyl) piperazine (PIPBS), N, N Sulfo such as' -bis (3-sulfopropyl) ethylenediamine (EDPS) And alkylalkylenediamines, among which the above-mentioned amino alcohols, sulfoalkylpiperazines having 2 to 4 carbon atoms, sulfoalkylalkylenediamines each having 2 or 3 carbon atoms in an alkyl group and an alkylene group are more preferable. Trometamol is preferred. These can be used individually by 1 type or in combination of 2 or more types.

  The blending amount of the organic amine in the ophthalmic composition of the present invention can be appropriately selected depending on the type thereof. For example, if it is trometamol, it is preferably 0.1 to 5 w / v with respect to the entire composition. (Mass / volume)%, and more preferably 0.5 to 3 w / v%. If the amount is too small, it may be difficult to sufficiently improve the stability of the tear film, and if it is too large, the feeling of use may be impaired.

  The type of fat-soluble vitamins used in the present invention is not particularly limited as long as it can be blended in an ophthalmic composition. Examples of such fat-soluble vitamins include retinol acetate. Vitamin A such as retinol palmitate, vitamin E such as tocopherol acetate (for example, d-α-tocopherol acetate), and the like. Among these, the above vitamin A is particularly preferable. These can be used individually by 1 type or in combination of 2 or more types as appropriate.

  The blending amount of the fat-soluble vitamins in the ophthalmic composition of the present invention can be appropriately selected depending on the type thereof. For example, if the vitamin A is retinol acetate, retinol palmitate, etc. 0.001 to 0.2 w / v%, that is, 1000 to 360,000 international units (hereinafter abbreviated as I.U.) / 100 ml is suitable, more preferably 0.01 to 0.1 w / v%, 10000-18000 I.V. U. / 100ml range. On the other hand, if it is vitamin E, such as tocopherol acetate (for example, d-α-tocopherol acetate), it is usually preferable to add 0.001 to 1.0 w / v% to the whole composition, more preferably. Is in the range of 0.01 to 0.3 w / v%. If the blending amount is too small, the effect of blending may not be sufficiently obtained, and if it is too large, the feeling of use may be impaired.

  The pH of the ophthalmic composition of the present invention is not particularly limited as long as it is an ophthalmically acceptable pH range. Usually, a pH range of 4 to 9 is preferable, and a pH range of 5 to 8 is more preferable. .5, more preferably pH 6-8.

  Further, the osmotic pressure of the ophthalmic composition of the present invention is not particularly limited, but it is usually preferable to adjust to a pressure ratio of 0.5 to 5 and more preferable to adjust to a pressure ratio of 0.8 to 2. Is preferred. In addition, when adjusting osmotic pressure, the adjustment method can be adjusted with the method normally performed, for example in an eye drop.

  The dosage form and form of the ophthalmic composition of the present invention are not particularly limited, and examples thereof include eye drops, eye washes, eye ointments, gels, and solid preparations that become liquid upon use. However, among these, the form of eye drops and eye wash is more preferable.

  The ophthalmic composition of the present invention, as long as the effects of the present invention are not hindered, can be applied to all preparations such as eye drops, eyewashes, eye ointments, gels, etc. other than the essential components described above. Various additives such as buffers, solubilizers, tonicity agents, stabilizers, thickeners, chelating agents, pH adjusters, cooling agents, and other pharmaceutically active ingredients are blended in usual amounts. be able to.

  Examples of the buffer include boric acid or a salt thereof (such as borax), citric acid or a salt thereof (such as sodium citrate), phosphoric acid or a salt thereof (such as sodium monohydrogen phosphate), tartaric acid or a salt thereof (tartaric acid) Sodium, etc.), gluconic acid or a salt thereof (sodium gluconate, etc.), acetic acid or a salt thereof (sodium acetate, etc.), various amino acids, or a combination thereof.

  Examples of solubilizers include polyoxyethylene higher fatty acid esters such as polyoxyethylene (p = 60) hydrogenated castor oil, polyoxyethylene sorbitan higher fatty acid esters such as polyoxyethylene (p = 20) sorbitan monooleate, and the like. Can be mentioned.

  Examples of the isotonic agent include sodium chloride and potassium chloride. Examples of the stabilizer include sodium edetate, cyclodextrin, sulfite, citric acid or a salt thereof.

  Examples of the thickener include polyvinyl pyrrolidone, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, polyvinyl alcohol, sodium hyaluronate, sodium chondroitin sulfate, and the like. In the present invention, among these, polyvinylpyrrolidone, hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, polyvinyl alcohol, and sodium hyaluronate are particularly suitable because they more stabilize the tear film.

  Examples of chelating agents include sodium edetate and sodium citrate. Examples of the pH adjuster include hydrochloric acid, citric acid or a salt thereof, boric acid or a salt thereof, phosphoric acid or a salt thereof, acetic acid or a salt thereof, tartaric acid or a salt thereof, sodium hydroxide, potassium hydroxide, and the like.

Examples of pharmaceutically active ingredients include decongestants (such as naphazoline hydrochloride, tetrahydrozoline hydrochloride, phenylephrine hydrochloride), anti-inflammatory / astringent agents (neostigmine methyl sulfate, ε-aminocaproic acid, allantoin, berberine chloride, zinc sulfate, lysozyme chloride, etc.) , antihistamines (diphenhydramine hydrochloride, isothipendyl hydrochloride, chlorpheniramine maleate, etc.), water-soluble vitamins (activated vitamin B _2, vitamin B _6, vitamin B _12), amino acids (L- potassium aspartate, L- aspartic acid Magnesium, aminoethylsulfonic acid, sodium chondroitin sulfate, etc.), sulfa drugs, fungicides (sulfur, isopropylmethylphenol, hinokitiol, etc.), local anesthetics (lidocaine, lidocaine hydrochloride, procaine hydrochloride, dibu hydrochloride) It can be appropriately blended in, etc.).

  The preparation method of the ophthalmic composition of the present invention is not particularly limited, and can be prepared according to a conventional method of its dosage form and form. For example, in the case of eye drops, first, vitamin A For example, fat-soluble vitamins such as alcohols can be prepared by solubilizing them in sterilized purified water using a nonionic surfactant or the like, and then adjusting the pH by adding each compounding component.

  The dosage amount of the ophthalmic composition of the present invention is not particularly limited as long as it is ophthalmically acceptable. For example, when used as an eye drop, 1 to 3 drops are usually administered 4 times a day. It is preferable to administer ~ 6 times.

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

[Example 1 and Comparative Examples 1 and 2]
According to the composition shown in Table 1, eye drops of Example 1 and Comparative Examples 1 and 2 were prepared according to a conventional method. For each eye drop, the stability of the tear film was evaluated by the following evaluation method using 6 subjects who complained of symptoms such as dryness and discomfort in the eyes by computer work for 3 hours or more. The results are shown in Table 2.

<Method of evaluating tear film stability>
The eye drop of Example 1 is instilled into one eye, and the eye drop of Comparative Example 1 or Comparative Example 2 is instilled into 2 to 3 drops, and 30 minutes later, 1% sodium fluorescein (1 μL) is used. The tear film break time (BUT) was measured. Here, BUT is the time from when the eye blinks until the tear film is first destroyed, and reflects the stability of the tear film.

  As is apparent from the results in Table 2, BUTs from Comparative Examples 1 and 2 were applied to the eye of Example 1 containing the specific organic amine (trometamol) and fat-soluble vitamins (retinol palmitate) of the present invention. , Indicating that the tear film stability was significantly improved. In the case of Comparative Example 2, irritation was felt.

[Examples 2 to 8]
According to the composition shown in Table 3, eye drops were prepared according to conventional methods to obtain eye drops of Examples 2 to 8. Each eye drop was instilled into one eye in the same manner as in Example 1 and the other eye. Comparative example 1 was instilled and each BUT was measured. As a result, in each of the examples, the result that the BUT was longer than that of the comparative example was obtained.

Example 9 Eyewash Retinol palmitate 0.003 g, d-α-tocopherol acetate 0.005 g, chlorpheniramine maleate 0.003 g, dipotassium glycyrrhizinate 0.025 g, trometamol 1.0 g, polyoxyethylene cured Castor oil (60) 0.1 g, sodium edetate 0.01 g, and benzalkonium chloride 0.003 g were added to sterilized purified water heated to 70 ° C., stirred and mixed, and then cooled to room temperature. Further, a solution prepared by dissolving 0.003 g of l-menthol and 0.001 g of dl-camphor in 0.5 g of propylene glycol in advance was added, and the total amount was adjusted to 100 mL with sterilized purified water, and filtered to obtain an eye wash.

  When the eye wash was performed using the eye wash of Example 9 and the BUT was measured, the result was that the BUT was longer than the composition without trometamol.

Claims (3)

  An eye drop comprising 0.1 to 5 w / v% trometamol and 0.001 to 0.3 w / v% tocopherol acetate.   The eye drop according to claim 1, which is used for prevention or treatment of dry eye.   A tear film stabilizer containing trometamol and tocopherol acetate.