JP5340498B1 - Ophthalmic composition for soft contact lenses - Google Patents

Abstract

An object of the present invention is to provide a technique for suppressing adsorption of pranoprofen and / or a salt thereof to SCL in an ophthalmic composition for SCL containing pranoprofen and / or a salt thereof. .
In an ophthalmic composition for SCL containing pranoprofen and / or a salt thereof, by setting the equivalent of a cation other than hydrogen ions to 140 mEq / L or less, pranoprofen and / or a salt thereof Adsorption to SCL can be effectively suppressed [selection figure] None

Description

  The present invention relates to an ophthalmic composition for soft contact lenses that can suppress the adsorption of pranoprofen and / or a salt thereof to the soft contact lens. The present invention also relates to a method for suppressing adsorption of pranoprofen and / or a salt thereof to a soft contact lens.

  Planoprofen and / or its salts have the effect of suppressing the biosynthesis of prostaglandins that cause inflammation and pain. In the ophthalmic field, alleviation of symptoms such as redness of the eyes and itching, blepharitis, and conjunctivitis It is widely used for the purpose of prevention or treatment of scleritis including suprasclitis, postoperative inflammation, anterior uveitis, and the like.

  Various preparation formulations of ophthalmic compositions using pranoprofen and / or salts thereof have also been reported. For example, Patent Document 1 reports that an aqueous topical solution containing pranoprofen and / or a salt thereof and an antihistamine can exhibit excellent anti-inflammatory and antipruritic effects. Patent Document 2 contains pranoprofen and / or a salt thereof in an amount of 0.01 to 2.0 w / v% and a specific vasoconstrictor such as naphazoline in an amount of 0.0005 to 0.1 w / v%. It has also been reported that eye drops can effectively exert the action of removing or reducing the hyperemia of the external eye part.

  On the other hand, in recent years, soft contact lenses (hereinafter sometimes abbreviated as SCL) that can be worn disposable or for a long period of time have been developed, and the number of SCL wearers is increasing. Therefore, in order to enhance the convenience of the SCL wearer, eye drops (SCL eye drops) that can be used while wearing the SCL are required. In addition to exerting a desired medicinal effect, the SCL eye drops need to be formulated so as not to adversely affect SCL. When the drug in the SCL eye drops is adsorbed on the SCL, the lens may be deformed, the feeling of use may be reduced, and the desired pharmacological effect may not be exerted on the ocular mucosa. In particular, suppression of drug adsorption on SCL has become a particularly important issue. Conventionally, in the eye drops for SCL, in order to suppress the adsorption of the drug to the SCL, a drug formulation including selection of a drug that is difficult to adsorb to the SCL and a composition of a component that suppresses the adsorption of the drug to the SCL has been adopted. ing.

  For example, Patent Document 3 discloses, as a pharmaceutical formulation that can suppress the adsorption of a basic drug composed of an amine compound having a secondary or tertiary amino group to SCL, together with the basic drug, an amino acid, a salt thereof, and an acidic mucopolysaccharide. , A salt thereof, or a cyclodextrin, and a composition for SCL having a pH set to 3.5 to 4.8 has been reported.

JP 2002-193805 A International Publication No. 01/87304 International Publication No. 2007/77783

  The present inventor has studied for practical application of an ophthalmic composition for SCL containing pranoprofen and / or a salt thereof. As a result, pranoprofen and / or a salt thereof has a property of being easily adsorbed on SCL. I faced the challenge of being. Furthermore, although pranoprofen and / or a salt thereof is structurally a basic drug, it behaves differently from other basic drugs such as neostigmine and chlorpheniramine in terms of adsorption to SCL. (See Reference Test Example 1 described later).

  Thus, it has been clarified by the present inventor that development of a formulation technique different from that of other basic drugs is required for suppressing adsorption of pranoprofen and / or a salt thereof to SCL. It was. However, in the past, there has been no report that actually examined the formulation technology for suppressing adsorption to SCL, focusing on pranoprofen and / or its salt in ophthalmic compositions for SCL such as eye drops for SCL. is there.

  Therefore, an object of the present invention is to provide a technique for suppressing adsorption of pranoprofen and / or a salt thereof to SCL in an ophthalmic composition for SCL containing pranoprofen and / or a salt thereof.

  The present inventor has intensively studied to solve the above problems. As a result, in an ophthalmic composition for SCL containing pranoprofen and / or a salt thereof, an equivalent of a cation other than hydrogen ions, pranoprofen and And / or finding that there is a relationship between the adsorptivity of the salt to SCL and setting the equivalent of a cation other than hydrogen ion to 140 mEq / L or less in the ophthalmic composition for SCL, It has been found that the adsorption of pranoprofen and / or a salt thereof to SCL can be effectively suppressed. The present invention has been completed by further studies based on this finding.

That is, this invention provides the invention of the aspect hung up below.
Item 1. An ophthalmic composition for soft contact lenses, comprising pranoprofen and / or a pharmaceutically acceptable salt thereof, wherein an equivalent amount of cations other than hydrogen ions is 140 mEq / L or less.
Item 2. Item 5. The ophthalmic composition for soft contact lenses according to Item 1, having a pH of 5.5-8.
Item 3. Item 3. The ophthalmic composition for soft contact lens according to Item 1 or 2, which is used for a soft contact lens classified by the US Food and Drug Administration as a group IV soft contact lens or a group III silicone hydrogel contact lens. .
Item 4. Item 3. The soft contact according to any one of Items 1 to 3, comprising at least one cation source selected from the group consisting of metal chlorides, metal salts of organic acids, metal salts of inorganic acids, and ammonium salts. Ophthalmic composition for lenses.
Item 5. Sodium chloride, potassium chloride, magnesium chloride, ammonium hydrogen phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium citrate, sodium nitrate, calcium acetate, and boron Item 5. The ophthalmic composition for soft contact lenses according to any one of Items 1 to 4, comprising at least one cation source selected from the group consisting of sand.
Item 6. The ophthalmic composition for soft contact lenses according to any one of Items 1 to 5, further comprising trometamol.
Item 7. Item 7. The ophthalmic composition for soft contact lenses according to any one of Items 1 to 6, which is an eye drop for soft contact lenses.
Item 8. An ophthalmic composition for soft contact lenses comprising pranoprofen and / or a pharmaceutically acceptable salt thereof, wherein a cation equivalent other than hydrogen ions is adjusted to 140 mEq / L or less, and the soft contact lens For inhibiting adsorption of pranoprofen and / or a pharmaceutically acceptable salt thereof.

  ADVANTAGE OF THE INVENTION According to this invention, adsorption | suction to pranoprofen and / or its salt to SCL can be suppressed, the bad influence to SCL can be prevented, and the medicinal effect of pranoprofen and / or its salt can be exhibited effectively. it can. Furthermore, according to the present invention, the cation equivalent in the ophthalmic composition for SCL is set within a predetermined range, thereby suppressing adsorption of pranoprofen and / or a salt thereof to SCL. Since it can set arbitrarily about the kind of compounding components other than a phen and / or its salt, there also exists an advantage that there are few restrictions on a pharmaceutical formulation.

1. Ophthalmic Composition for SCL The ophthalmic composition for SCL of the present invention contains pranoprofen and / or a pharmaceutically acceptable salt thereof, and the equivalent of a cation other than hydrogen ion is 140 mEq / L or less. It is characterized by that. Hereinafter, the ophthalmic composition for SCL of the present invention will be described in detail. In the present specification, “an ophthalmic composition for SCL” refers to a composition that is used in the ophthalmic field and used in contact with SCL. In the present specification, the unit of concentration of each component “w / v%” indicates mass to volume percentage and is synonymous with g / 100 mL. Furthermore, “mEq / L” is the milliequivalent of the cation contained in the composition 1L, and indicates a value obtained by multiplying the millimolar concentration of the cation contained in the composition 1L by the valence.

  The ophthalmic composition for SCL of the present invention contains pranoprofen and / or a pharmaceutically acceptable salt thereof.

  Planoprofen is also known as α-methyl-5H- [1] benzopyrano [2,3-b] pyridine-7-acetic acid, and is a known compound known to have anti-inflammatory activity in the ophthalmic field. .

  The salt of pranoprofen is not particularly limited as long as it is pharmaceutically acceptable. For example, metal salts such as sodium salt, potassium salt, calcium salt, magnesium salt, aluminum salt; triethylamine salt, diethylamine salt, Examples thereof include organic base salts such as morpholine salt and piperazine salt. These pranoprofen salts may be used alone or in combination of two or more.

  In the ophthalmic composition for SCL of the present invention, one kind selected from pranoprofen and a salt thereof may be used alone, or two or more kinds may be used in combination. Of the pranoprofen and salts thereof, pranoprofen is preferable.

  In the ophthalmic composition for SCL of the present invention, the concentration of pranoprofen and / or a salt thereof is appropriately set according to the use etc. of the ophthalmic composition for SCL. 0.0 w / v%, preferably 0.01 to 1.0 w / v% or 0.01 to 0.1 w / v%, more preferably 0.05 to 0.2 w / v%.

  In the ophthalmic composition for SCL of the present invention, the equivalent of cations other than hydrogen ions is set to 140 mEq / L or less. It has been found by the present inventor that pranoprofen and / or a salt thereof inherently has the property of adsorbing to SCL, and according to the present invention, cation equivalents other than hydrogen ions are thus obtained. Is set to a predetermined range, it is possible to suppress the adsorption of pranoprofen and / or a salt thereof to SCL. In the present invention, “a cation other than hydrogen ion” refers to all cations present in the ophthalmic composition for SCL, regardless of the type of metal ion, polyatomic ion, complex ion, etc. Shows positive ions. In the present invention, the valence of the cation is not particularly limited, but it is preferably a monovalent or divalent cation, and more preferably a monovalent cation.

  From the viewpoint of more effectively suppressing the adsorption of pranoprofen and / or a salt thereof to SCL, the upper limit of the cation equivalent other than hydrogen ions in the ophthalmic composition for SCL of the present invention is usually 140 mEq. / L, preferably 120 mEq / L, more preferably 90 mEq / L, more preferably 70 mEq / L, 75 mEq / L, 55 mEq / L, or 50 mEq / L, particularly preferably 45 mEq / L, most preferably 35 mEq / L. Can be mentioned.

  In addition, if the cation equivalent other than hydrogen ions is too low, there is a risk of causing a change in the lens size of the SCL. Therefore, the ophthalmic composition for SCL of the present invention has a pH range that can suppress the change in the lens size of the SCL. It is desirable to adjust or set so that cations other than hydrogen ions are equal to or greater than a certain equivalent. For example, if the change in the lens size of SCL is suppressed by adjusting the pH, 0 mEq / L is given as the lower limit of the cation equivalent other than hydrogen ions in the ophthalmic composition for SCL of the present invention. It is done. In addition, for example, if the change in the SCL lens size is suppressed by setting a cation other than hydrogen ions to a certain equivalent or more, a cation other than hydrogen ions in the ophthalmic composition for SCL of the present invention is used. The lower limit of the ion equivalent is usually 20 mEq / L, preferably 30 mEq / L.

  That is, for the cation equivalent other than hydrogen ion in the ophthalmic composition for SCL of the present invention, the adsorption of pranoprofen and / or a salt thereof to SCL is more effectively suppressed, and the lens size of SCL From the viewpoint of also suppressing the change of the above, it is usually adjusted in the range of 0 to 140 mEq / L, preferably 20 to 120 mEq / L, more preferably 20 to 90 mEq / L, more preferably 20 to 75 mEq / L, 20 It is adjusted to ˜70 mEq / L, or 20 to 55 mEq / L, 20 to 50 mEq / L, particularly preferably 20 to 45 mEq / L, and most preferably 30 to 35 mEq / L.

  Specific examples of cations other than hydrogen ions include sodium ions, potassium ions, magnesium ions, calcium ions, iron (II) ions, iron (III) ions, copper (I) ions, copper (II) ions, Metal ions such as zinc ions and aluminum ions; polyatomic ions such as ammonium ions; complex ions such as tetraammine zinc (II) ions and tetraammine copper (II) ions. The ophthalmic composition for SCL of the present invention may contain one kind of cation other than hydrogen ion alone or two or more kinds as long as the above equivalent is satisfied.

  In the ophthalmic composition for SCL of the present invention, in order to set the equivalent of cation other than hydrogen ion within the above range, a cation other than hydrogen ion is added among the components of the ophthalmic composition for SCL. What is necessary is just to adjust content of the cation supply source to produce. Examples of such a cation supply source include metal salts, ammonium salts, and metal complexes. These cation sources may also be in the form of hydrates.

  In the ophthalmic composition for SCL of the present invention, the present invention is intended to suppress the change in lens size of SCL, improve the stability of the ophthalmic composition for SCL, impart desired osmotic pressure, impart desired buffering action, etc. The ophthalmic composition for SCL is selected from the group consisting of metal chlorides, metal salts of organic acids, metal salts of inorganic acids, and ammonium salts as long as the equivalents of cations other than hydrogen ions are satisfied. Preferably, at least one cation source is included.

  Among the cation sources, the type of metal chloride is not particularly limited as long as it is pharmaceutically acceptable. For example, examples of the metal constituting the metal chloride include sodium, potassium, magnesium, calcium, iron (II), iron (III), copper (I), copper (II), zinc, and aluminum. Specific examples of the organic acid metal salt include sodium chloride, potassium chloride, magnesium chloride and the like. Among these metal chlorides, sodium chloride, potassium chloride, calcium chloride, and magnesium chloride are preferable, sodium chloride and potassium chloride are more preferable, and sodium chloride is particularly preferable. These metal chlorides may be used alone or in combination of two or more.

  Further, among the cation sources, the type of the organic acid metal salt is not particularly limited as long as it is pharmaceutically acceptable. For example, the organic acid constituting the metal salt of the organic acid includes acetic acid, citric acid, oxalic acid, tartaric acid and the like. Moreover, as a metal which comprises the metal salt of organic acid, the thing similar to the metal which comprises the said metal chloride is mentioned. Specific examples of the metal salt of an organic acid include sodium acetate, potassium acetate, sodium citrate, potassium citrate, sodium oxalate, potassium oxalate, sodium tartrate, potassium tartrate, and the like. These metal salts of organic acids may be in the form of hydrates. Among these metal salts of organic acids, sodium citrate, potassium citrate, potassium acetate, and calcium acetate are preferable, and sodium citrate and calcium acetate are more preferable. These metal salts of organic acids may be used alone or in combination of two or more.

  Further, among the cation source, the metal salt of the inorganic acid is not particularly limited as long as it is pharmaceutically acceptable. For example, phosphoric acid, nitric acid, boric acid etc. are mentioned as an inorganic acid which comprises the metal salt of an inorganic acid. Moreover, as a metal which comprises the metal salt of an inorganic acid, the thing similar to the metal which comprises the said metal chloride is mentioned. Specific examples of inorganic acid metal salts include disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium nitrate, potassium nitrate, sodium borate, and borax. It is done. These metal salts of inorganic acids may be in the form of hydrates. Among these metal salts of organic acids, disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium nitrate, and borax are preferable. These inorganic acid metal salts may be used alone or in combination of two or more.

  Of the cation source, the ammonium salt is not particularly limited as long as it is pharmaceutically acceptable. Specific examples of the ammonium salt include ammonium of an inorganic acid such as ammonium phosphate. Ammonium salts of inorganic acids may be used alone or in combination of two or more.

  Among the cation supply sources, sodium chloride, potassium chloride, magnesium chloride, and the like are preferable components from the viewpoints of suppressing the change in the lens size of SCL, improving the stability of the ophthalmic composition for SCL, and imparting a desired osmotic pressure. Ammonium hydrogen phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium citrate, sodium nitrate, calcium acetate, and borax; And potassium chloride; sodium chloride is a particularly preferred component.

  About content of the said cation supply source in the ophthalmic composition for SCL of this invention, it sets suitably in the range which satisfies the equivalent of cations other than the hydrogen ion mentioned above.

  The ophthalmic composition for SCL of the present invention may contain a buffer. Specific examples of the buffer include a phosphate buffer, a borate buffer, a citrate buffer, a tartaric acid buffer, an acetate buffer, a Tris buffer, and an amino acid. The buffer is usually composed of a combination of an acid and a base, or a compound containing a carboxyl group and an amino group, and these buffer components are appropriately selected. Specific examples of the buffer component include trometamol, boric acid, phosphoric acid, citric acid, tartaric acid, acetic acid, hydrochloric acid, malein, in addition to the organic metal salt or inorganic acid metal salt that can be a cation source. Examples include acids and amino acids. Among these buffer components, trometamol is preferably used from the viewpoint that an excellent buffering action can be imparted without increasing the cation equivalent other than hydrogen ions in the ophthalmic composition for SCL of the present invention.

  About the density | concentration of the said buffer component in the ophthalmic composition for SCL of this invention, it sets suitably according to the kind etc., and when using a cation supply source as the said buffer component, the cation mentioned above Although it is set so as to satisfy the equivalent range, for example, the concentration of the total amount of the buffer component is usually 0.01 to 10 w / v%, preferably 0.05 to 5 w / v%, more preferably 0.2. ˜2 w / v%.

  The ophthalmic composition for SCL of the present invention may contain other pharmacological components as necessary in addition to the above components. Examples of pharmacological ingredients that can be incorporated include dipotassium glycyrrhizinate, allantoin, epsilon aminocaproic acid, bromfenac, ketorolac tromethamine, nepafenac, berberine chloride, berberine sulfate, sodium azulenesulfonate, zinc sulfate, zinc lactate, lysozyme hydrochloride Anti-histamines such as chlorpheniramine maleate and diphenhydramine hydrochloride; antiallergic agents such as cromoglycate sodium, ketotifen fumarate, acitazanolast, amlexanox, pemirolast potassium, tranilast, ibudilast; , Ofloxacin, lomefloxacin, levofloxacin, gentamicin, gatifloxacin and other antibacterial agents; ascorbic acid, flavin adenine dinucleotide nato Vitamins such as um, cyanocobalamin, pyridoxine hydrochloride, tocopherol acetate, retinol acetate, retinol palmitate, panthenol, calcium pantothenate, sodium pantothenate; amino acids such as aspartic acid, taurine, sodium chondroitin sulfate, neostigmine Anticholinesterase agents such as methyl sulfate; vasoconstrictors such as naphazoline, tetrahydrozoline, epinephrine, ephedrine, phenylephrine, dl-methylephedrine; therapeutic agents for keratoconjunctival epithelial disorder such as sodium hyaluronate; sulfadiazine, sulfisoxazole, sulfisomidine , Sulfadimethoxine, sulfamethoxypyridazine, sulfamethoxazole, sulfaethidol, sulfamethomidine Sulfaphenazole, sulfaguanidine, phthalidyl Rusuru phosphatidyl azole, sulfa drugs such as succinyl Rusuru phosphatidyl azoles and the like. The compounds exemplified here may be in the form of a salt as long as they are pharmaceutically acceptable, and may be in the form of other salts. These pharmacological components may be used alone or in combination of two or more.

  The concentration of these pharmacological components is appropriately set according to the type of pharmacological component, the use of the SCL ophthalmic composition, etc., but the pharmacological component contains cations other than hydrogen ions in the SCL ophthalmic composition. In the case of generating, it is set within a range satisfying the cation equivalent other than the hydrogen ion described above.

  In addition to the above components, the ophthalmic composition for SCL of the present invention contains, as necessary, isotonic agents, solubilizers, viscous bases, chelating agents, cooling agents, pH adjusters, antiseptics, and the like. You may contain additives, such as an agent, a stabilizer, and surfactant.

  Examples of the isotonic agent include saccharides such as sorbitol, glucose and mannitol; polyhydric alcohols such as glycerin and propylene glycol; boric acid and the like. These isotonic agents may be used alone or in combination of two or more.

  Examples of the solubilizer include nonionic surfactants such as polyoxyethylene sorbitan monooleate, polyoxyethylene hydrogenated castor oil, tyloxapol, and pluronic; polyhydric alcohols such as glycerin and macrogol. These solubilizers may be used alone or in combination of two or more.

  Examples of the viscous base include water-soluble polymers such as polyvinylpyrrolidone, polyethylene glycol, polyvinyl alcohol, carboxyvinyl polymer, xanthan gum, sodium chondroitin sulfate, sodium hyaluronate; hypromellose, hydroxyethyl cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl Examples thereof include celluloses such as methyl cellulose and sodium carboxymethyl cellulose. These viscous bases may be used individually by 1 type, and may be used in combination of 2 or more type.

  Examples of the chelating agent include edetate, citric acid or a salt thereof. These chelating agents may be used individually by 1 type, and may be used in combination of 2 or more type.

  Examples of the refreshing agent include l-menthol, borneol, camphor, and eucalyptus oil. These refreshing agents may be used alone or in combination of two or more.

  Examples of the pH adjuster include alkalis such as sodium hydroxide and potassium hydroxide; acids such as acetic acid, citric acid, hydrochloric acid, phosphoric acid and tartaric acid. These pH adjusters may be used alone or in combination of two or more.

  Examples of the preservative include sorbic acid or a salt thereof, benzoic acid or a salt thereof, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, chlorobutanol, chlorohexidine gluconate, boric acid, dehydroacetic acid or Examples thereof include salts thereof, benzalkonium chloride, benzethonium chloride, benzyl alcohol, zinc chloride, parachlorometaxylenol, chlorcresol, phenethyl alcohol, polydronium chloride, thimerosal, and dibutylhydroxytoluene. These preservatives may be used individually by 1 type, and may be used in combination of 2 or more type.

  Examples of the stabilizer include polyvinyl pyrrolidone, sulfite, monoethanolamine, glycerin, propylene glycol, cyclodextrin, dextran, ascorbic acid, edetate, taurine, tocopherol, dibutylhydroxytoluene and the like. These stabilizers may be used individually by 1 type, and may be used in combination of 2 or more type.

  Examples of the surfactant include nonionic surfactants such as tyloxapol, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene block copolymer, polyoxyethylene sorbitan fatty acid ester, octoxynol; alkyldiaminoethylglycine, Amphoteric surfactants such as lauryldimethylaminoacetic acid betaine; anionic surfactants such as alkyl sulfate, N-acyl taurate, polyoxyethylene alkyl ether phosphate, polyoxyethylene alkyl ether sulfate; alkyl pyridinium salts; And cationic surfactants such as alkylamine salts. These surfactants may be used individually by 1 type, and may be used in combination of 2 or more type.

  The concentration of these additives may be set as appropriate depending on the type of additive and the use of the SCL ophthalmic composition, but the additive to be added is other than hydrogen ions in the SCL ophthalmic composition. In the case of generating cations, the cation is set within a range satisfying cation equivalents other than the hydrogen ions described above.

  Although it does not restrict | limit especially about pH of the ophthalmic composition for SCL of this invention, For example, 5.5-8, Preferably it is 5.5-7.5, More preferably, it is 6-7.5. In particular, by setting the pH within the range of 5.5 to 7.5, it is possible to suppress a change in the SCL lens size even if the cation equivalent other than hydrogen ions is low.

  The formulation form of the ophthalmic composition for SCL of the present invention is not limited as long as it contains water as a base, and may be any one of an aqueous solution, a suspension, an emulsion, etc., preferably an aqueous solution. Shape.

  The ophthalmic composition for SCL of the present invention may be produced according to a method known per se according to its use. For example, it may be produced using the method described in the 16th revised Japanese Pharmacopoeia General Rules for Preparations. it can.

  The ophthalmic composition for SCL of the present invention is an eye drop that can be instilled even when wearing SCL (an eye drop for SCL); an eye wash that can be washed even while wearing an SCL (an eye wash for SCL); an SCL mounting solution, and a multipurpose solution for SCL It is used as a contact lens care product such as an SCL cleaning solution and an SCL storage solution. Among these, Preferably, the eye drop for SCL, the eye wash for SCL, More preferably, the eye drop for SCL is mentioned.

  The ophthalmic composition for SCL of the present invention can be used for all types of SCL regardless of ionicity, moisture content, etc., and is classified into Group I (ionic) classified by the US Food and Drug Administration (FDA). Less than 1 mol% monomer, less than 50% moisture content), group II (less than 1 mol% ionic monomer, more than 50% moisture content), group III (more than 1 mol% ionic monomer, less than 50% moisture content), and It can be used for any SCL of Group IV (ionic monomer 1 mol% or more, water content 50% or more). The ophthalmic composition for SCL of the present invention can also be used for silicone hydrogel contact lenses. Among these SCLs, Group I, Group IV, and silicone hydrogel contact lenses (Group III) have a property of more easily adsorbing pranoprofen and / or a salt thereof. There is a strong demand for suppression of adsorption of profen and / or its salts. On the other hand, the ophthalmic composition for SCL of the present invention adsorbs pranoprofen and / or a salt thereof to Group I SCL, Group IV SCL, and Group III silicone hydrogel contact lenses. It can be effectively suppressed. In view of the advantages of the present invention, the SCL to be applied is preferably a Group I SCL, a Group IV SCL, and a Group III silicone hydrogel contact lens, more preferably a Group IV SCL and a Group III. Silicone hydrogel contact lenses, particularly preferably Group IV SCL.

  Moreover, in the ophthalmic composition for SCL of the present invention, the material of the SCL to be applied is not particularly limited, and for example, any SCL material registered in the United States USAN (United States Adopted Names). Good. Specific examples of SCL materials to which the ophthalmic composition for SCL of the present invention is applied include Polyconcon, nelfilcon A, ocfilcon D, vifilcon A, etafilcon A, alafilcon A, balafilcon A, alpha Afilon, , MethafilconA, atlafilconA, crofilconA, deltafilconA, droxifilconA, focofilconA, genfilconA, goafilconA, hefilconA, hefilconB, hefilconC conA, hioxifilconA, hioxifilconB, lidofilconA, lidofilconB, mafilconA, methafilconB, mipafilconA, nelfilconA, netrafilconA, ocufilconA, ocufilconB, ocufilconC, ocufilconD, ocufilconE, ocufilconF, ofilconA, omafilconA, perfilconA, phemfilconA, polymacon, surfilconA, tefilconA, vifilconA, xylofilconA, etc. Is mentioned. Among these, preferably, Polymacon, nelfilconA, ocufilconD, vifilconA, etafilconA, otrafilconA, balafilconA, alphafilconA, bufilconA, lotrafilconA, asmofilconA, tetrafilconA, senofilconA, vasurfilconA, methafilconA; more preferably, Polymacon, nelfilconA, ocufilconD, vifilconA, etafilconA , Otrafilcon A, balafilcon A; particularly preferred are etafilcon A, vifilcon A, ocufilcon D, balafilcon A.

2. The present invention also relates to an ophthalmic composition for SCL containing pranoprofen and / or a pharmaceutically acceptable salt thereof, in the ophthalmic composition containing pranoprofen and / or a salt thereof. Provided is a method for suppressing adsorption of pranoprofen and / or a salt thereof to SCL, wherein the ion equivalent is adjusted to 140 mEq / L or less. The adsorption suppression method is useful for providing the SCL ophthalmic composition with an inhibitory action of pranoprofen and / or a salt thereof on the SCL during the production of the SCL ophthalmic composition.

  In the method for inhibiting adsorption of the present invention, pranoprofen and / or a pharmaceutically acceptable salt thereof, a cation equivalent other than hydrogen ion, a pharmacological component or an additive added to an ophthalmic composition for SCL The type, formulation form and use of the ophthalmic composition for SCL, the type of SCL to be applied, and the like are as described in the column of “1. Ophthalmic composition for SCL”.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

Test Example 1: Effect of cation equivalent on adsorption of pranoprofen on various SCLs (1)
The test liquid was prepared by mixing each component shown in Table 1 by a conventional method. 2 ml of each test solution was put in a vial, and 2 pieces of SCL were immersed therein and shaken at 25 ° C. for 2 hours or more. Further, 2 ml of each test solution was put in a vial and shaken at 25 ° C. for 2 hours or more without immersing SCL. After shaking, the pranoprofen content in each test solution was measured by liquid chromatography, and the amount of pranoprofen adsorbed on SCL was calculated according to the following formula. When shaking under the condition that SCL is immersed in the test solution, the adsorption of pranoprofen to SCL reaches an equilibrium state within 2 hours. Therefore, if the shaking time is set to 2 hours or more, pranoprofen on SCL is reached. It has been confirmed that there is no effect on the measured value of the amount of adsorbed.

In this test, the following seven types of SCL were used, and the amount of pranoprofen adsorbed on each SCL was determined.
Lens 1: Group I, trade name “Medalist (registered trademark) plus” (manufactured by Bochrom Japan), USAN name: polymacon
Lens 2: Group II, trade name “Daily's (registered trademark) Aqua” (Cibavision), USAN name: nelfilcon A
Lens 3: Group IV, product name "One Day Aqua" (manufactured by Coopervision), USAN name: ocufilcon D
Lens 4: Group IV, trade name “Focus (registered trademark) 2 week” (Cibavision), USAN name: vifilcon A
Lens 5: Group IV, trade name “One Day Accuview (registered trademark)” (manufactured by Johnson & John Don Medical), USAN name: etafilcon A
Lens 6: Silicone hydrogel contact lens, Group I, trade name “Air Optics (registered trademark)” (Cibavision), USAN name: otrafilcon B
Lens 7: Silicone hydrogel contact lens, Group III, trade name “Medalist (registered trademark) Fresh Fit (registered trademark)” (manufactured by Bosch Lom Japan), USAN name: balafilconA

  The obtained results are shown in Table 1. Comparative Example 2 has a cation equivalent of about 169 mEq / L of the total amount of sodium ions (145 mEq / L) and potassium ions (24.1 mEq / L) in tears, and can be used as a reference for comparison. (Japan Biochemical Society, Biochemistry Data Book I 1st edition, Tokyo Chemical Doujin, Tokyo, 1979). From this result, in the cation equivalent test solution (Comparative Examples 1 and 2) in which cations other than hydrogen ions (sodium ions) are equal to or higher than tear fluid (Comparative Examples 1 and 2), the amount of pranoprofen adsorbed in any SCL There were many. On the other hand, in the test solutions (Examples 1 to 9) in which cations other than hydrogen ions are 140 mEq / L or less, compared with Comparative Example 2 which is a cation equivalent equivalent to tears, pranoprofen to SCL Adsorption was suppressed. In particular, for the SCL of Group I (Lens 1), the SCL of Group IV (Lens 3 to 4), and the silicone hydrogel contact lens (Lens 7) of Group III, the test solution of Comparative Examples 1 to 3 is a plano. Although the adsorption of prophen was remarkable, the adsorption of pranoprofen could be effectively suppressed in the test solutions of Examples 1 to 9.

Reference Test Example 1: Effect of cation equivalent on adsorption of basic drugs other than pranoprofen on SCL To confirm the effect of cation equivalent on adsorption of basic drugs other than pranoprofen on SCL Adsorption of neostigmine methyl sulfate and chlorpheniramine maleate on SCL was evaluated. Specifically, a test solution was prepared by mixing each component shown in Table 2 by a conventional method, and neostigmine into SCL was prepared in the same manner as in Test Example 1 except that one SCL was placed in a vial. The adsorption amount of methyl sulfate and chlorpheniramine maleate was measured. In this test, the lens 5 (group IV) used in Test Example 1 was used as SCL. Further, after shaking, the content of neostigmine methyl sulfate or chlorpheniramine maleate in each test solution was measured by liquid chromatography, and the amount adsorbed on SCL was calculated according to the following formula.

  The obtained results are shown in Table 2. As is clear from Table 2, as the cation equivalents other than hydrogen ions decreased, the adsorbed amounts of neostigmine methyl sulfate and chlorpheniramine maleate increased. Therefore, it was suggested that the adsorption to SCL is suppressed by lowering the cation equivalent other than the hydrogen ion is an effect peculiar to pranoprofen and / or a salt thereof.

Test Example 2: Effect of cation type on adsorption of pranoprofen to SCL A test solution was prepared by mixing the components shown in Table 3 by a conventional method, and in the same manner as in Test Example 1, The amount of pranoprofen adsorbed on SCL was measured. In this test, the lens 5 (group IV) used in Test Example 1 was used as SCL.

  The obtained results are shown in Table 3. From this result, in the test solution (Comparative Examples 4 and 6) having 168 mEq / L each of sodium ions or potassium ions alone, and in the test solution having a total amount of sodium ions and potassium ions of 168 mEq / L (Comparative Example 5), SCL The amount of pranoprofen adsorbed on the surface was large. On the other hand, in the test solution (Examples 10 to 16) in which the total amount of sodium ions and potassium ions is 121 mEq / L or less, the adsorption of pranoprofen to SCL irrespective of the types and ratios of sodium ions and potassium ions. Was effectively suppressed. From the above results, it has been clarified that the adsorption of pranoprofen to SCL can be suppressed by setting the equivalent of cation other than hydrogen ion to a predetermined value or less regardless of the type of cation.

Test Example 3: Influence of various inorganic and organic acid metal salts on adsorption of pranoprofen to SCL A test solution was prepared by mixing the components shown in Table 4 by a conventional method. In the same manner, the amount of pranoprofen adsorbed on SCL was measured. In this test, the lens 5 (group IV) used in Test Example 1 was used as SCL.

  Table 4 shows the obtained results. As apparent from Table 4, regardless of the difference between the inorganic acid and organic acid constituting the metal salt serving as the cation supply source, a test solution having a cation other than hydrogen ion of about 168 mEq / L (Comparative Examples 7 to In 12), the amount of pranoprofen adsorbed on SCL was large, but in the test solutions (Examples 17 to 22) in which cations other than hydrogen ions were 140 mEq / L or less, the effect of adsorbing pranoprofen on SCL was effective. Was suppressed. Also from the results of this test, the adsorption of pranoprofen to SCL involves cations other than hydrogen ions regardless of the type of cation, and the equivalent amount of cations other than hydrogen ions is below a predetermined value. It was confirmed that the adsorption of pranoprofen to SCL can be suppressed by setting to.

Test Example 4: Effect of divalent cation on adsorption of pranoprofen to SCL A test solution was prepared by mixing each component shown in Table 5 by a conventional method, and in the same manner as in Test Example 1, The amount of pranoprofen adsorbed on SCL was measured. In this test, the lens 5 (group IV) used in Test Example 1 was used as SCL.

  The results obtained are shown in Table 5. As shown in Table 5, even in the case of calcium ions or magnesium ions, the amount of pranoprofen adsorbed on SCL was large in the test solution (Comparative Examples 13 to 16) having an equivalent weight of 168 mEq / L or more. In the test solutions having these cation equivalents of 140 mEq / L or less (Examples 23 to 32), it was possible to effectively suppress the adsorption of pranoprofen to SCL. That is, also from the result of this test, cations other than hydrogen ions are involved in the adsorption of pranoprofen to SCL, and by setting the equivalent of cations other than hydrogen ions to a predetermined value or less, It was confirmed that the adsorption of pranoprofen to SCL can be suppressed.

Test Example 5: Effect of cations on adsorption of pranoprofen to SCL in the case of containing low concentrations (0.01 and 0.02 w / v%) of pranoprofen Mixing each component shown in Table 6 by a conventional method The test solution was prepared by the same method as in Test Example 1, and the amount of pranoprofen adsorbed on SCL was measured. In this test, the lens 5 (group IV) used in Test Example 1 was used as SCL.

  The results obtained are shown in Table 6. As is apparent from Table 6, even when pranoprofen is contained at low concentrations of 0.01 and 0.02 w / v%, by setting the cation equivalent other than hydrogen ions to 140 mEq / L or less, It was possible to effectively suppress the adsorption of pranoprofen to SCL.

Test Example 6: Effect of cation equivalent on adsorption of pranoprofen on various SCLs (2)
A test solution was prepared by mixing the components shown in Table 7 by a conventional method, and the amount of pranoprofen adsorbed on SCL was measured in the same manner as in Test Example 1. In this test, the lens 5 (group IV) used in Test Example 1 was used as SCL.

  The results obtained are shown in Table 7. Also from this result, it was confirmed that the adsorption of pranoprofen to SCL can be suppressed as the cation equivalents other than hydrogen ions are lower. Further, from the comparison between Example 40 and Examples 41 to 43, sodium chloride was used alone as a source of cations other than hydrogen ions, trometamol was used as a pH adjuster, and cation equivalents other than hydrogen ions were further set to 55 mEq. It was revealed that the adsorption of pranoprofen to SCL can be remarkably suppressed by setting to / L or less, 50 mEq / L or less, or 45 mEq / L or less.

Test Example 7: Effect of Cation Equivalent on SCL Size Each component shown in Table 8 was mixed by a conventional method to prepare a test solution. After immersing the lens 5 (Group IV) used in Test Example 1 in 2 ml of each test solution at room temperature for 3 hours, use a high-precision two-dimensional dimension measuring device VM-8040 (Keyence Co., Ltd.). Diameter was measured. The control test solution shown in Table 7 is used when measuring the diameter of a contact lens specified in “Optics and optical instruments -Contact lenses-Saline solution for contact lens testing” (ISO10344, 1996). This is a standard saline solution, and the larger the difference in lens diameter compared to the control test solution, the greater the change in size of the SCL.

  Table 8 shows the obtained results. From this result, it was recognized that the SCL diameter tends to increase as the cation equivalent decreases as compared to the control test solution. Moreover, the tendency for the diameter of SCL to become small was recognized by lowering | hanging pH. From this result, if the cation equivalents other than hydrogen ions are in the range of 29 to 140 mEq / L, it is possible to suppress the size change of SCL within the allowable range while suppressing the adsorption of pranoprofen to SCL. Became clear.

Claims (7)

Ophthalmic composition for soft contact lenses used for Group IV soft contact lenses classified by the US Food and Drug Administration or Group III silicone hydrogel contact lenses,
An ophthalmic composition for soft contact lenses, comprising pranoprofen and / or a pharmaceutically acceptable salt thereof, wherein an equivalent amount of cations other than hydrogen ions is 140 mEq / L or less. The ophthalmic composition for soft contact lenses according to claim 1, having a pH of 5.5-8. Metal chlorides, metal salts of organic acids, metal salts of inorganic acids, and at least one cation source is selected from the group consisting of ammonium salts, software according to claim 1 or 2 An ophthalmic composition for contact lenses. Sodium chloride, potassium chloride, magnesium chloride, ammonium hydrogen phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium citrate, sodium nitrate, calcium acetate, and boron The ophthalmic composition for soft contact lenses according to any one of claims 1 to 3 , comprising at least one cation source selected from the group consisting of sand. The ophthalmic composition for soft contact lenses according to any one of claims 1 to 4 , further comprising trometamol. The ophthalmic composition for soft contact lenses according to any one of claims 1 to 5 , which is an eye drop for soft contact lenses. Soft contact lens classification by the US Food and Drug Administration for group IV soft contact lenses or group III silicone hydrogel contact lenses containing pranoprofen and / or a pharmaceutically acceptable salt thereof. in soft contact lenses for ophthalmic composition is, and adjusting the cation equivalent other than hydrogen ions below 140 mEq / L, is pranoprofen and / or a pharmaceutically acceptable to the soft contact lenses To suppress salt adsorption.