JP5678530B2 - Ophthalmic composition for soft contact lenses - Google Patents

Description

  The present invention relates to a soft contact lens composition containing azulene sulfonic acid and / or a salt thereof, and a method for suppressing adsorption of azulene sulfonic acid and / or a salt thereof in a soft contact lens in this composition.

  When a soft contact lens is mounted, the lens surface is dried, pollen and contaminants from the outside are likely to adhere to the lens, and inflammation is likely to occur in the eye wearing the lens. In order to improve the inflammation of the eye at the time of wearing such a contact lens, it has been desired to develop a composition for soft contact lenses containing azulenesulfonic acid or a salt thereof which is an anti-inflammatory component.

  However, among the components used in ophthalmic preparations, there are drugs that adsorb onto a soft contact lens and adversely affect the lens or the eyes, and adsorption suppression techniques are being investigated for such drugs. Up to now, as a technique for suppressing the adsorption of a drug to a soft contact lens, an invention for suppressing the adsorption of a fat-soluble vitamin with a polymer compound and a nonionic surfactant (see Patent Document 1), adsorption of dipotassium glycyrrhizinate That suppresses the adsorption of alginic acid with an amino acid or the like (see Patent Document 3), and the invention that suppresses the adsorption of a basic drug with a low pH and an amino acid or the like (Patent Document 4) (See Patent Document 5 and Patent Document 6) in which a terpenoid compound such as menthol is suppressed with a surfactant such as polyoxyethylene sorbitan ester.

JP 2001-158734 A Japanese Patent Laid-Open No. 2001-2563 JP 2008-24701 A Table 2007-077773 JP-A-11-130667 Japanese Patent Laid-Open No. 11-180858

The present inventors have found that azulenesulfonic acid and / or a salt thereof has a property of being easily adsorbed on the surface of a soft contact lens including a polymer having a pyrrolidone group, among soft contact lenses. Therefore, when a preparation containing azulene sulfonic acid and / or a salt thereof is applied to the soft contact lens, azulene sulfonic acid and / or a salt thereof accumulates inside the lens over time depending on the amount of tears and usage. As a result, the physical properties (appearance) of the lens may change, the feeling of use during wearing may decrease, and adverse effects such as side effects may occur.
The present invention has been made in view of the above circumstances, and in a composition for soft contact lenses containing azulenesulfonic acid and / or a salt thereof, adsorption of azulenesulfonic acid and / or a salt thereof to the soft contact lens can be suppressed, And it aims at providing the adsorption | suction suppression technique by which the eye irritation by it does not arise. That is, an ophthalmic preparation containing azulenesulfonic acid and / or a salt thereof suitable for use by a soft contact lens wearer, and a method for suppressing adsorption of azulenesulfonic acid and / or a salt thereof to a soft contact lens are provided.

  As a result of intensive studies to achieve the above object, the present inventors have selected and blended polyoxyethylene castor oil among the surfactants into the composition containing azulenesulfonic acid and / or a salt thereof. Adsorption to a soft contact lens containing a polymer having a pyrrolidone group of azulene sulfonic acid and / or a salt thereof is suppressed, and eye irritation does not occur, so that an ophthalmic preparation suitable for use by a soft contact lens wearer can be obtained It has been found that the present invention has been made.

Accordingly, the present invention provides the following soft contact lens composition and adsorption suppression method.
[1] A composition for soft contact lenses, comprising (A) azulenesulfonic acid and / or a salt thereof, and (B) polyoxyethylene castor oil.
[2] The composition for soft contact lenses according to [1], wherein the amount of component (A) is 0.001 to 0.1 W / V%.
[3] The composition for soft contact lenses according to [1] or [2], wherein (B) polyoxyethylene castor oil has 3 to 60 moles of ethylene oxide added.
[ 4 ] The soft contact lens composition according to any one of [1] to [3] , wherein the amount of component (B) is 3 to 5 W / V%.
[ 5 ] The composition for soft contact lenses according to any one of [1] to [ 4 ] , wherein the composition is for soft contact lenses containing a polymer having a pyrrolidone group.
[ 6 ] Software according to any one of [1] to [ 5 ], which is an eye drop for a contact lens wearer, a contact lens wear liquid, an eye wash for a contact lens wearer, a contact lens removal liquid, or a contact lens care agent. Contact lens composition.
[ 7 ] The amount of adsorption of (A) azulenesulfonic acid and / or a salt thereof to the soft contact lens is reduced by blending (B) polyoxyethylene castor oil, [1] to [ 6 ] ] The composition for soft contact lenses in any one of.
[ 8 ] (A) In the ophthalmic preparation containing azulenesulfonic acid and / or a salt thereof, (B) polyoxyethylene castor oil is blended so as to be 3 to 5 W / V%, (A) A method for suppressing adsorption to a soft contact lens comprising a polymer having a pyrrolidone group as a component.

  ADVANTAGE OF THE INVENTION According to this invention, in the composition for soft contact lenses containing azulenesulfonic acid and / or its salt, adsorption | suction to the soft contact lens containing the polymer which has a pyrrolidone group of azulenesulfonic acid and / or its salt is suppressed. It is possible to provide a composition for a soft contact lens that can be used and that does not cause eye irritation.

  Hereinafter, the present invention will be described in detail.

  The soft contact lens composition of the present invention is a soft contact lens composition containing (A) azulene sulfonic acid and / or a salt thereof and (B) polyoxyethylene castor oil.

(A) Azulenesulfonic acid and / or salt thereof Azulenesulfonic acid and / or salt thereof is an anti-inflammatory component. Examples of the salt of azulene sulfonic acid include sodium salt and potassium salt.

  The content of (A) azulenesulfonic acid and / or a salt thereof is preferably 0.001 to 0.1 W / V% (mass / volume% (g / 100 mL), the same applies hereinafter) in the soft contact lens composition, 0.003-0.05 W / V% is more preferable, and 0.004-0.025 W / V% is more preferable. If the content is less than 0.001 W / V%, the anti-inflammatory effect of azulenesulfonic acid and / or its salt may be insufficient, and if it exceeds 0.1 W / V%, the composition has a deep purple color. In the case of overflowing from the eyes after instillation, there is a possibility that the clothes become dirty, and eye irritation may be felt when the upper limit is significantly exceeded.

(B) Polyoxyethylene castor oil In this invention, adsorption | suction to the soft contact lens of azulenesulfonic acid and / or its salt can be suppressed notably by mix | blending polyoxyethylene castor oil. These can use a commercially available thing, and it is preferable to use the product made from BASF Corporation and NOF Corporation. Further, as the nonionic surfactant, a nonionic surfactant other than the component (B), for example, polyoxyethylene monooleate (20) sorbitan (polysorbate 80), polyoxyethylene hydrogenated castor oil 60, or the like is used. If this occurs, an adsorption suppression effect is recognized, but eye irritation may be felt.

  The content of the component (B) is preferably 3 to 5 W / V% in the ophthalmic composition, more preferably 3.5 to 5 W / V%, and still more preferably 4 to 5 W / V%. If the blending amount is too small, the adsorption suppressing effect of sodium azulene sulfonate is insufficient, and if it exceeds 5 W / V%, eye irritation may be felt. 3-60 are preferable, as for the ethylene oxide addition mole number of polyoxyethylene castor oil, More preferably, it is 6-50, More preferably, it is 10-40. If the number of moles of ethylene oxide added is small, the solubility in water tends to decrease, and if it is too large, the adsorption suppression effect may decrease.

  In addition, as a nonionic surfactant, it replaces with (B) component of this invention, and other nonionic surfactant, for example, monooleic acid polyoxyethylene (20) sorbitan (polysorbate 80), polyoxyethylene hardening When castor oil 60 or the like is used, it is not possible to satisfy both the effects of adsorption suppression and low irritation.

  In the soft contact lens composition of the present invention, various components used in the ophthalmic composition can be blended as necessary within a range not impairing the effects of the present invention. Examples of preferable ingredients include drugs, buffers, stabilizers, thickeners, tonicity agents, solubilizers, antioxidants, preservatives, and refreshing agents.

  Examples of drugs (pharmaceutical active ingredients) include other vitamins (eg, retinol acetate, retinol palmitate, pyridoxine hydrochloride), decongestants (eg, naphazoline hydrochloride, tetrahydrozoline hydrochloride, phenylephrine hydrochloride, epinephrine, ephedrine hydrochloride) Dl-methylephedrine hydrochloride, tetrahydrozoline nitrate, naphazoline nitrate, etc.), anti-inflammatory / astringent (eg, neostigmine methyl sulfate, ε-aminocaproic acid, allantoin, berberine chloride, zinc sulfate, zinc lactate, dipotassium glycyrrhizinate, ammonium glycyrrhizinate Glycyrrhetinic acid), antihistamines (eg diphenhydramine hydrochloride, diphenhydramine chlorpheniramine maleate, etc.), amino acids (eg potassium L-aspartate, L-aspartate) Magnesium Ragin acid, aminoethyl sulfonic acid), sulfa (e.g., sulfamethoxazole, sulfisoxazole, etc.), antiallergic agents (e.g., can be appropriately compounded sodium cromoglycate, etc.).

  The effective content of each drug can be selected as the content of each drug. From the viewpoint of eye irritation, composition stability, etc., 0.001 to 5 W / V% in the composition for soft contact lenses It is preferable that it is the range of these.

  As the buffer, for example, citric acid, sodium citrate, boric acid, borax, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, glacial acetic acid, trometamol, and sodium hydrogen carbonate are preferably used. Among these, citric acid, boric acid, borax, and trometamol are preferable. The content of the buffering agent is preferably in the range of 0.003 to 4 W / V% in the soft contact lens composition.

  Examples of the stabilizer include sodium edetate, edetic acid, α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin and the like. Edetic acids have the effect of maintaining the stability of the system, and cyclodextrins have the effect of suppressing the adsorption of components that are easily adsorbed to soft contact lenses (for example, benzalkonium chloride). The content of the stabilizer is preferably in the range of 0.003 to 2 W / V% in the soft contact lens composition.

  Examples of the thickening agent include cellulose polymer compounds such as methyl cellulose, hypromellose and hydroxyethyl cellulose, polyvinyl polymer compounds such as povidone and polyvinyl alcohol, liquid paraffin, carboxyvinyl polymer, and polyethylene glycol. The content of the thickening agent is preferably in the range of 0.003 to 3 W / V% in the soft contact lens composition.

  Examples of the isotonic agent include potassium chloride, sodium chloride, glycerin and the like. The content of the tonicity agent is preferably in the range of 0.001 to 3 W / V% in the soft contact lens composition.

  Examples of solubilizers include surfactants such as polyhydric alcohols such as propylene glycol, polyethylene glycol, and sorbitol, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid esters, and proxamers. As polyoxyethylene hydrogenated castor oil, besides polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 100, and the like can be used. Examples of polyoxyethylene sorbitan fatty acid esters include polyoxyethylene (20) sorbitan (polysorbate 80) monooleate, polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene sorbitan monostearate (polysorbate 20). Polysorbate 60), polyoxyethylene sorbitan tristearate (polysorbate 65) and the like can be used. The content of the solubilizing agent is preferably in the range of 0.001 to 3 W / V% in the soft contact lens composition.

  Examples of the antioxidant include dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), hydroquinone, propyl gallate, sodium bisulfite and the like. The content of the antioxidant is preferably in the range of 0.001 to 1 W / V% in the soft contact lens composition.

  Examples of the preservative include parabens such as benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, sorbic acid, potassium sorbate, chlorobutanol, and paraoxybenzoic acid ester. The content of the preservative is preferably in the range of 0.001 to 0.5 W / V% in the soft contact lens composition.

  In addition to using the preservative, it is possible to increase the antiseptic effect by an antiseptic composition essentially comprising trometamol, boric acid and edetic acid, which is preferable in the present invention.

  Examples of the refreshing agent include camphor and cool mint no. 71212, geraniol, mint water, menthol, borneol, eucalyptus oil, fennel oil, bergamot oil, linalool, N-ethyl-p-menthane-carboxyamide (for example, WS-3, Takasago International Corporation) and the like. The content of the refreshing agent is preferably in the range of 0.0001 to 0.1 W / V% in the soft contact lens composition.

  The composition for soft contact lenses of the present invention can be produced by, for example, a known production method with the balance being water. For example, after dissolving each of the above components in sterilized purified water, water such as ion exchange water, or a mixed solvent with an alcohol such as ethanol, the pH is adjusted, and if necessary, the osmotic pressure is adjusted to a pH adjusting agent, It can be obtained by appropriately adjusting with a tonicity agent.

  The pH (20 ° C.) of the soft contact lens composition of the present invention is not particularly limited as long as it is within the range acceptable for ophthalmic compositions, but is preferably 3.5 to 8.0, more preferably 5.0 to 7.5, more preferably 6.0 to 7.3. Within the above range, the eye irritation is particularly low and good. The pH is measured at 20 ° C. using a pH osmometer (HSMO-1, Toa DKK). As the pH adjuster, sodium hydroxide, potassium hydroxide, hydrochloric acid and the like are preferable.

  The obtained composition is filled in a known plastic container such as polyethylene, polypropylene or polyethylene terephthalate (a material containing an ultraviolet ray prevention agent or a dye is preferable for the stability of the contents), and is subjected to packaging such as film packaging. And can be provided as an aqueous ophthalmic formulation.

  The composition for soft contact lenses of the present invention can be used as an eye drop, a contact lens mounting solution, a contact lens eye wash, a contact lens removal solution, or a contact lens care agent. Specifically, eye drops for soft contact lens users used while wearing soft contact lenses, soft contact lens wearing solutions used when wearing soft contact lenses, eyewashes used while wearing soft contact lenses, software Soft contact lens remover used when removing contact lenses, soft contact lens care agent (cleaning solution, rinsing solution, disinfecting solution, preserving solution, etc., and MPS for soft contact lens that can be cleaned, rinsed, disinfected and stored at the same time ) Is preferable. Among these, it is suitable as an eye drop for a contact lens wearer, a contact lens wearing solution, an eye wash for a contact lens wearer, or a contact lens removing solution.

  The type of soft contact lens to which the composition for soft contact lens of the present invention can be applied is not particularly limited, and it is a soft contact lens that is repeatedly used, a one-day disposable soft contact lens, a one-week disposable soft contact lens. Can be used for any of the two week disposable soft contact lenses. Moreover, it can be used not only for all four categories of soft contact lenses by the US Food and Drug Administration (FDA) but also for silicone hydrogel lenses.

  Soft contact lenses are manufactured from many chemically synthesized materials. Monomers constituting soft contact lenses include alkyl methacrylates such as hydroxyethyl methacrylate, methyl methacrylate, ethylene glycol dimethacrylate, etc. Nonionic water-soluble monomers such as polyvinyl alcohol, N-vinylpyrrolidone, N, N-dimethylacrylamide, etc. Examples of ionic monomers include methacrylic acid.

  The composition for soft contact lenses of the present invention is particularly suitable for soft contact lenses containing a polymer having a pyrrolidone group such as N-vinylpyrrolidone. The polymer may have alkyl methacrylate, methacrylic acid, a monomer containing silicon or fluorine, polyvinyl alcohol, or the like as a structural unit. The proportion of N-vinylpyrrolidone is not particularly limited, but is preferably 1 to 90 parts by mass with respect to 100 parts by mass of the total amount of polymerizable monomers. Soft contact lenses containing a polymer having N-vinylpyrrolidone as a structural unit include Precision UV: Ciba Vision Co., Ltd., Menicon Soft S: Menicon, Breath Oh: Toray Co., Ltd., Bushrom Medalist Premier: Bochrom Japan )) And the like.

  The method for suppressing adsorption to a soft contact lens containing a polymer having a pyrrolidone group of (A) azulenesulfonic acid and / or a salt thereof according to the present invention is for a soft contact lens containing (A) azulenesulfonic acid and / or a salt thereof. (B) polyoxyethylene castor oil is mix | blended with a composition, Preferably it mix | blends so that it may become 3-5 W / V%. Other suitable components, contents and the like are the same as those in the ophthalmic composition.

  EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example.

[Examples 1-14, Comparative Examples 1-3]
As shown in Tables 1 to 3, each compounding component was dissolved in sterilized purified water according to a conventional method, and then each solution was sterile filtered to prepare a soft contact lens composition. About each obtained formulation, pH (20 degreeC) was measured and the sodium azulenesulfonate adsorption test with respect to the following soft contact lens was done. Moreover, the eye irritation after instillation was evaluated by the following method. The eye drop was prepared by aseptic filtration of each solution. The results are also shown in the table.

[Adsorption test of sodium azulenesulfonate on soft contact lenses: n = 3]
Two types of soft contact lenses were used: Precision UV (Cibavision Co., Ltd.) containing a polymer having a pyrrolidone group and Boschrom Medalist Premier (Boschrom Japan Co., Ltd.). Each lens material is as follows.
Precision UV: N-vinyl pyrrolidone, methyl methacrylate boschrom medalist premiere: N-vinyl pyrrolidone, hydroxyethyl methacrylate, trimethylsiloxacimethacryloxypropylsilane derivative

  One lens was permeated into 5 mL of the composition for soft contact lenses at 37 ° C. for 7 days, and the amount of residual sodium azulene sulfonate was quantified by liquid chromatography. The composition for a soft contact lens in which the lens is not immersed is determined in the same manner as a control, and the ratio of the control to the amount of sodium azulene sulfonate is based on the following formula, and the lens adsorption rate (%) of sodium azulene sulfonate for the two types of lenses Was calculated.

Lens adsorption rate of sodium azulene sulfonate (%) = [(amount of sodium azulene sulfonate for control−amount of sodium azulene sulfonate for residual liquid) / amount of sodium azulene sulfonate for control × 100]

  One soft contact lens composition was measured three times for each of two types of lenses. The average adsorption rate (%) was calculated for each lens type, and the result of the adsorption suppression effect on the soft contact lens was shown based on the following evaluation criteria from the average adsorption rate.

<Adsorption suppression evaluation criteria for soft contact lenses>
A: Average adsorption rate of sodium azulenesulfonate is less than 5% B: Average adsorption rate of sodium azulenesulfonate is 5% or more and less than 7.5% C: Average adsorption rate of sodium azulenesulfonate is 7.5% or more and 10 Less than% D: Average adsorption rate of sodium azulenesulfonate is 10% or more and less than 12.5% E: Average adsorption rate of sodium azulenesulfonate is 12.5% or more

  According to the results of Examples and Comparative Examples, the composition containing 3 to 5 W / V% polyoxyethylene castor oil suppresses the adsorption of sodium azulene sulfonate to the soft contact lens and has no eye irritation. Was recognized.

[Evaluation of eye irritation]
Three soft contact lens users were instilled with 3 drops of the soft contact lens composition while wearing the soft contact lens, and the eye irritation after the instillation was evaluated based on the following evaluation criteria.
<Evaluation criteria for eye irritation>
○: I do not feel stimulation △: I feel some stimulation ×: I feel stimulation

Claims (8)

  A composition for soft contact lenses comprising (A) azulene sulfonic acid and / or a salt thereof and (B) polyoxyethylene castor oil. (A) Component amount is 0.001-0.1 W / V%, The composition for soft contact lenses of Claim 1 characterized by the above-mentioned. The composition for soft contact lenses according to claim 1 or 2, wherein (B) polyoxyethylene castor oil has 3 to 60 moles of added ethylene oxide. (B) Composition amount is 3-5 W / V%, The composition for soft contact lenses of any one of Claims 1-3 characterized by the above-mentioned. The composition for soft contact lenses according to any one of claims 1 to 4, wherein the composition is for soft contact lenses containing a polymer having a pyrrolidone group. The composition for soft contact lenses according to any one of claims 1 to 5 , which is an eye drop for a contact lens wearer, a contact lens wear solution, an eye wash for a contact lens wearer, a contact lens removing solution, or a contact lens care agent. object. The amount of adsorption of (A) azulene sulfonic acid and / or a salt thereof on a soft contact lens is reduced by blending (B) polyoxyethylene castor oil, according to any one of claims 1 to 6. The composition for soft contact lenses according to Item.   (A) In the ophthalmic preparation containing azulenesulfonic acid and / or a salt thereof, (B) polyoxyethylene castor oil is blended so as to be 3 to 5 W / V%, (A) A method for suppressing adsorption to a soft contact lens containing a polymer having a component pyrrolidone group.