JP6366583B2 - Ophthalmic composition for zwitterionic soft contact lenses - Google Patents

Description

  The present invention relates to an ophthalmic composition for a zwitterionic soft contact lens that exhibits a clear appearance and can suppress adsorption of pranoprofen and / or a salt thereof to the zwitterionic soft contact lens. The present invention also relates to a method for suppressing adsorption of pranoprofen and / or a salt thereof to a zwitterionic 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 ophthalmic agent containing pranoprofen and chondroitin sulfate or a salt thereof can alleviate irritation caused by pranoprofen. However, an ophthalmic composition that can be used when wearing a contact lens requires a pharmaceutical formulation that can suppress the adsorption of the drug to the contact lens. However, the pharmaceutical technology disclosed in Patent Document 1 The influence is not considered at all, and the formulation of the ophthalmic composition that can be used when wearing contact lenses is not disclosed.

  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. Conventionally, many non-ionic and anionic materials have been used as SCL materials, but in recent years, proteins, lipids, cell fragments, etc. in tears are accumulated on the lens surface. As a material of SCL capable of suppressing the above, those showing zwitterionic properties have been put into practical use. Therefore, in order to enhance the convenience for the zwitterionic SCL wearer, eye drops that can be used while wearing the zwitterionic SCL (eye drops for zwitterionic SCL) are required. In addition to exhibiting a desired medicinal effect, the zwitterionic SCL eye drops need to be formulated so as not to adversely affect the zwitterionic SCL. When a drug in an eye drop for zwitterionic SCL is adsorbed to 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 the case of ophthalmic SCL eye drops, suppression of drug adsorption on zwitterionic SCL is 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 2 discloses, as a pharmaceutical formulation that can suppress 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 2005-239682 A International Publication No. 2007/77783

  However, in Patent Document 2, attention is paid to pranoprofen and / or a salt thereof, and no study has been made on its adsorption property to zwitterionic SCL. Since amine compounds having secondary or tertiary amino groups include a wide variety of drugs, the adsorption properties of drugs on SCL vary depending on the structure other than amino groups. Furthermore, since the characteristics of the lens surface of SCL vary greatly depending on the presence or absence of ionicity, the type of ionicity, etc., examination of the drug adsorption characteristics on SCL according to the SCL material is required. In fact, the present inventor has confirmed that zwitterionic SCL has a specific problem that, unlike nonionic SCL and anionic SCL, the adsorptivity of pranoprofen and / or its salt is extremely high. (See Test Example 1 below).

  Furthermore, in Patent Document 2, it is essential to set the pH to 4.8 or less. However, the present inventors have determined that the ophthalmic composition for SCL containing pranoprofen and / or a salt thereof has a pH of 4.8. When adjusted to the following extent, it has been confirmed that there is a problem that white turbidity occurs and the appearance properties that can be put into practical use cannot be exhibited (see Test Example 1 described later).

  In order to commercialize an ophthalmic composition for zwitterionic SCL containing pranoprofen and / or a salt thereof against the background of such prior art, the application of pranoprofen and / or a salt thereof to zwitterionic SCL There is a demand for setting a pharmaceutical formulation exhibiting a clear appearance property after sufficiently considering the adsorption characteristics.

  Accordingly, the present invention provides a zwitterionic SCL ophthalmic composition containing pranoprofen and / or a salt thereof, which has a clear appearance property, and pranoprofen and / or a salt thereof to zwitterionic SCL. It aims at providing the technique which suppresses adsorption | suction.

  As a result of intensive studies to solve the above problems, the present inventor has formulated chondroitin sulfate and / or a salt thereof in an ophthalmic composition for zwitterionic SCL containing pranoprofen and / or a salt thereof. Further, it was found that by setting the pH to 5.5 or more, a clear appearance property can be realized, and adsorption of pranoprofen and / or a salt thereof to the zwitterionic 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. Containing pranoprofen and / or a pharmaceutically acceptable salt thereof, chondroitin sulfate and / or a pharmaceutically acceptable salt thereof, and having a pH of 5.5 or more, An ophthalmic composition for zwitterionic soft contact lenses.
Item 2. Item 2. The ophthalmic composition for zwitterionic soft contact lenses according to Item 1, wherein the chondroitin sulfate and / or pharmaceutically acceptable salt thereof is sodium chondroitin sulfate.
Item 3. Item 3. The ophthalmic composition for zwitterionic soft contact lenses according to Item 1 or 2, wherein the chondroitin sulfate and / or a pharmaceutically acceptable salt thereof is contained in an amount of 0.05 to 3 w / v%.
Item 4. Item 10. The ophthalmic composition for zwitterionic soft contact lenses according to any one of Items 1 to 3, wherein the pH is 5.5 to 9.
Item 5. Item 5. The ophthalmic composition for zwitterionic soft contact lenses according to any one of Items 1 to 4, wherein pranoprofen and / or a pharmaceutically acceptable salt thereof is contained in an amount of 0.001 to 0.5 w / v%. .
Item 6. Item 6. The ophthalmic composition for a zwitterionic soft contact lens according to any one of Items 1 to 5, which is an eye drop for a zwitterionic soft contact lens.
Item 7. In an ophthalmic composition for zwitterionic soft contact lenses containing pranoprofen and / or a pharmaceutically acceptable salt thereof, chondroitin sulfate and / or a pharmaceutically acceptable salt thereof are blended, and the pH is adjusted. A method for suppressing adsorption of pranoprofen and / or a pharmaceutically acceptable salt thereof to a zwitterionic soft contact lens, which is adjusted to 5.5 or more.
Item 8. Zwitterionicity of a liquid preparation containing pranoprofen and / or a pharmaceutically acceptable salt thereof and chondroitin sulfate and / or a pharmaceutically acceptable salt thereof and having a pH of 5.5 or more Use for the manufacture of an ophthalmic composition for soft contact lenses.
Item 9. A solution containing pranoprofen and / or a pharmaceutically acceptable salt thereof and chondroitin sulfate and / or a pharmaceutically acceptable salt thereof and having a pH of 5.5 or higher is zwitterionic. A method for suppressing adsorption of pranoprofen and / or a pharmaceutically acceptable salt thereof to a zwitterionic soft contact lens, comprising a step of contacting the soft contact lens.

  According to the ophthalmic composition for zwitterionic SCL of the present invention, it is possible to suppress the adsorption of pranoprofen and / or a salt thereof to the zwitterionic SCL, so that the planopro without adversely affecting the zwitterionic SCL. The medicinal effects of phen and / or a salt thereof can be effectively exhibited. In the ophthalmic composition for zwitterionic SCL of the present invention, chondroitin sulfate and / or a salt thereof not only suppresses adsorption of pranoprofen and / or a salt thereof to zwitterionic SCL, The mucous membrane can be moisturized to alleviate discomfort when wearing zwitterionic SCL.

  Moreover, according to the ophthalmic composition for zwitterionic SCL of the present invention, while containing pranoprofen and / or a salt thereof, white turbidity caused by setting to about pH 4.8 or less can be suppressed, An ophthalmic composition for zwitterionic SCL that exhibits a clear appearance can be provided. In the present specification, “clear” refers to a state in which white turbidity is not caused by pranoprofen and / or a salt thereof, and is not limited to colorless and clear, but is colored and clear that is colored by other components. It is a concept that also includes.

1. Ophthalmic composition for zwitterionic SCL The ophthalmic composition for zwitterionic SCL of the present invention comprises pranoprofen and / or a pharmaceutically acceptable salt thereof, chondroitin sulfate and / or a pharmaceutically acceptable salt thereof. And a salt having a pH of 5.5 or higher. Hereinafter, the ophthalmic composition for zwitterionic SCL of the present invention will be described in detail. In the present specification, the “ophthalmic composition for zwitterionic SCL” refers to a composition that is used in the ophthalmic field and used in contact with zwitterionic 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.

  The ophthalmic composition for zwitterionic SCL of the present invention contains pranoprofen and / or a 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 zwitterionic 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 zwitterionic SCL of the present invention, the concentration of pranoprofen and / or a salt thereof is appropriately set according to the use of the ophthalmic composition for zwitterionic SCL, for example, 0.001-0.5 w / v%, preferably 0.01-0.2 w / v%, more preferably 0.01-0.1 w / v%.

  The ophthalmic composition for zwitterionic SCL of the present invention further contains chondroitin sulfate and / or a salt thereof.

  Chondroitin sulfate is a compound known as an acidic mucopolysaccharide having a structure in which sulfuric acid is bound to a sugar chain in which two sugars of D-glucuronic acid and N-acetyl-D-galactosamine are repeated.

  The salt of chondroitin sulfate is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include alkali metal salts such as sodium salt and potassium salt. Among these salts, sodium salts are preferable. These chondroitin sulfate salts may be used singly or in combination of two or more.

  The origin of chondroitin sulfate and / or salt thereof used in the present invention is not particularly limited, and is derived from organisms such as mammals and fish cartilage (eg salmon and shark cartilage), derived from microorganisms, and synthetic products. Any of these may be used. Among these, those derived from fish cartilage are particularly preferable.

  Further, the average molecular weight of the chondroitin sulfate ester and / or salt thereof used in the present invention is not particularly limited, and examples thereof include 1000 to 50000, preferably 5000 to 50000, and more preferably 5000 to 20000. Here, the average molecular weight is the viscosity average molecular weight obtained from the intrinsic viscosity measured by the 16th revision Japanese Pharmacopoeia General Test Method Viscosity Measurement Method 1 Method Capillary Viscometer Method.

  In the ophthalmic composition for zwitterionic SCL of the present invention, one type may be selected from chondroitin sulfate and a salt thereof, or two or more types may be used in combination. Among chondroitin sulfates and salts thereof, chondroitin sulfate salts are preferable, and chondroitin sulfate sodium is more preferable.

  In the ophthalmic composition for zwitterionic SCL of the present invention, the concentration of chondroitin sulfate and / or a salt thereof is not particularly limited, and examples thereof include 0.05 to 3 w / v%. The concentration of chondroitin sulfate and / or salt thereof in the ophthalmic composition for zwitterionic SCL of the present invention from the viewpoint of further improving the effect of suppressing the adsorption of pranoprofen and / or salt thereof to zwitterionic SCL Is preferably 0.05 to 1 w / v%, more preferably 0.05 to 0.5 w / v%.

  The pH of the ophthalmic composition for zwitterionic SCL of the present invention is set to 5.5 or higher. In the ophthalmic composition for zwitterionic SCL of the present invention, the pronoprophene and / or salt thereof together with the chondroitin sulfate ester and / or salt thereof is set to such a pH range, so that While suppressing adsorption of phen and / or a salt thereof to the zwitterionic SCL, it becomes possible to suppress white turbidity and exhibit a clear appearance property.

  The pH of the ophthalmic composition for zwitterionic SCL of the present invention is to provide a clear appearance property while further effectively suppressing the adsorption of pranoprofen and / or its salt to the zwitterionic SCL. From a viewpoint, Preferably it is 5.5-9, More preferably, it is 6-8, More preferably, 6.5-8 is mentioned.

  In order to adjust the pH of the ophthalmic composition for zwitterionic SCL of the present invention to the above range, a pH adjuster or buffer generally used in ophthalmic compositions may be used. 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 buffer include phosphate buffer, borate buffer, citrate buffer, tartaric acid buffer, acetate buffer, amino acid, trometamol, and the like. These buffering agents may be used alone or in combination of two or more.

  The ophthalmic composition for zwitterionic SCL of the present invention may contain a pharmacological component other than pranoprofen and / or a salt thereof, if necessary, in addition to the above components. Examples of such pharmacological components include dipotassium glycyrrhizinate, allantoin, epsilon aminocaproic acid, bromfenac, ketorolac tromethamine, nepafenac, berberine chloride, berberine sulfate, sodium azulene sulfonate, 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 and taurine, neostigmine methyl sulfate, etc. Anti-cholinesterase agents; vasoconstrictors such as naphazoline, tetrahydrozoline, epinephrine, ephedrine, phenylephrine, dl-methylephedrine; keratoconjunctival epithelial disorders such as sodium hyaluronate; sulfadiazine, sulfisoxazole, sulfisomidine, sulfadimethoxine, Famethoxypyridazine, sulfamethoxazole, sulfaethidol, sulfamethomidine, sulfaphenazole, sulf Guanidine, 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.

  About the density | concentration of these pharmacological components, it sets suitably according to the use etc. of the kind of pharmacological component, and the ophthalmic composition for zwitterionic SCL.

  In addition to the above components, the ophthalmic composition for zwitterionic SCL of the present invention contains, as necessary, isotonic agents, solubilizers, thickeners, chelating agents, cooling agents, preservatives. Further, additives such as stabilizers and surfactants may be contained.

  Examples of the isotonic agent include saccharides such as sorbitol, glucose and mannitol; polyhydric alcohols such as glycerin and propylene glycol; salts such as sodium chloride; 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 thickener include water-soluble polymers such as polyvinyl pyrrolidone, polyethylene glycol, polyvinyl alcohol, carboxyvinyl polymer, xanthan gum, sodium hyaluronate; hypromellose, hydroxyethyl cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethylcellulose. Examples thereof include celluloses such as sodium. These thickeners may be used alone or in combination of two or more.

  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 preservative include sorbic acid or a salt thereof, benzoic acid or a salt thereof, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, chlorobutanol, chlorhexidine gluconate, boric acid, dehydroacetic acid or a salt thereof Benzalkonium chloride, benzethonium chloride, benzyl alcohol, zinc chloride, parachlorometaxylenol, chlorcresol, phenethyl alcohol, polydronium chloride, thimerosal, dibutylhydroxytoluene and the like. 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.

  About the density | concentration of these additives, it sets suitably according to the use etc. of the kind of additive, the ophthalmic composition for zwitterionic SCL.

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

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

  The ophthalmic composition for zwitterionic SCL of the present invention comprises eye drops that can be instilled even while wearing zwitterionic SCL (eye drops for zwitterionic SCL); eyewash that can be washed even while wearing zwitterionic SCL (zwitterionic) SCL eyewash); used as a contact lens care product such as a zwitterionic SCL mounting solution, a zwitterionic SCL multipurpose solution, a zwitterionic SCL cleaning solution, and a zwitterionic SCL storage solution. Among these, preferably, an eye drop for zwitterionic SCL, an eye wash for zwitterionic SCL, and more preferably an eye drop for zwitterionic SCL.

  The zwitterionic SCL to which the present invention is applied is an SCL composed of a polymer containing a monomer containing a cationic group and a monomer containing an anionic group as an ionic monomer. Specific examples of the zwitterionic SCL include SCLs composed of a polymer containing a cationic group such as a quaternary ammonium salt and an anionic group such as a carboxyl group, a sulfonic acid group, and a phosphoric acid group. The material and manufacturing method thereof are described in, for example, JP-A-10-197831.

  In addition, the zwitterionic SCL to which the present invention is applied may have either a high water content or a low water content, but preferably a high water content, that is, a group IV ( Examples thereof include those classified into ionic monomers of 1 mol% or more and water content of 50% or more.

2. Method for inhibiting adsorption of pranoprofen and / or salt thereof to zwitterionic SCL (1)
The present invention also provides a zwitterionic SCL ophthalmic composition containing pranoprofen and / or a pharmaceutically acceptable salt thereof, containing chondroitin sulfate and / or a salt thereof, and a pH of 5. Provided is a method for suppressing the adsorption of pranoprofen and / or a salt thereof to zwitterionic SCL, characterized by adjusting to 5 or more. The adsorption inhibiting method is useful for imparting the adsorption inhibiting action of pranoprofen and / or a salt thereof to the zwitterionic SCL to the ophthalmic composition for zwitterionic SCL.

  In the adsorption suppression method of the present invention, the type and concentration of pranoprofen and / or its pharmaceutically acceptable salt, the type and concentration of chondroitin sulfate and / or its salt, and ophthalmic use for zwitterionic SCL PH of the composition, types of pharmacological ingredients and additives to be incorporated into the ophthalmic composition for zwitterionic SCL, formulation form and use of the ophthalmic composition for zwitterionic SCL, and the zwitterionic SCL to be applied The type and the like are as described in the column of “1. Ophthalmic composition for zwitterionic SCL”.

3. Method for inhibiting adsorption of pranoprofen and / or salt thereof to zwitterionic SCL (2)
The present invention also includes pranoprofen and / or a pharmaceutically acceptable salt thereof, chondroitin sulfate and / or a pharmaceutically acceptable salt thereof, and has a pH of 5.5 or more. Provided is a method for suppressing the adsorption of pranoprofen and / or a salt thereof to a zwitterionic SCL, comprising a step of bringing the liquid into contact with the zwitterionic SCL.

  In the adsorption suppression method of the present invention, the type and concentration of pranoprofen and / or its pharmaceutically acceptable salt, the type and concentration of chondroitin sulfate and / or its salt, and ophthalmic use for zwitterionic SCL PH of the composition, types of pharmacological ingredients and additives to be incorporated into the ophthalmic composition for zwitterionic SCL, formulation form and use of the ophthalmic composition for zwitterionic SCL, and the zwitterionic SCL to be applied The type and the like are as described in the column of “1. Ophthalmic composition for zwitterionic SCL”. Moreover, what is necessary is just to set suitably the method of making the said liquid agent contact zwitterionic SCL in the adsorption | suction suppression method of this invention according to the use of the said liquid agent. For example, if the liquid preparation is an eye drop, the liquid preparation may be applied to the eye wearing the zwitterionic 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
The test liquid was prepared by mixing each component shown in Table 1 by a conventional method. While observing the appearance of each of the obtained test solutions, the presence or absence of white turbidity was evaluated by measuring the turbidity (absorbance at 660 nm).

  Moreover, 3 mL of each test solution was put into a vial, 1 piece of SCL was immersed in it, and it shaked at 25 degreeC for 2 hours or more. Further, 3 mL of each test solution was placed 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 three types of SCL were used, and the amount of pranoprofen adsorbed on each SCL was determined.
Lens 1: Zwitterionic, Group IV, trade name “Seed 1dayPure UP (Uruoi Plus)” (registered trademark) manufactured by Seed Co., Ltd.), lens material: 2-hydroxyethyl methacrylate (HEMA), quaternary ammonium group -Containing methacrylate compounds, carboxyl group-containing methacrylate compounds, methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA)
Lens 2: Anionic, Group IV, trade name “One Day Accuview (registered trademark)” (manufactured by Johnson & Johnson Medical), USAN name: etafilcon A
Lens 3: Silicone hydrogel contact lens, Group I, trade name “Air Optics 2 Week (registered trademark)” (Cibavision), USAN name: lotrafilcon B

  The obtained results are shown in Table 1. From these results, in all test solutions having a pH of 4.5 or less (Comparative Example 6-9), pranoprofen was clouded, whereas test solutions having a pH of 5.5 or more (Example 1-5 and Comparative Example 1). In -5), it was colorless and clear and had good appearance properties. In addition, even when it had a colorless and clear appearance, when it did not contain sodium chondroitin sulfate (Comparative Example 1-5), the adsorption of pranoprofen to zwitterionic SCL was strongly observed. On the other hand, when chondroitin sulfate sodium was included (Example 1-5), the adsorption of pranoprofen to zwitterionic SCL could be suppressed. In addition, pranoprofen was hardly adsorbed to the anionic SCL and the silicone hydrogel contact lens irrespective of the presence or absence of chondroitin sulfate sodium.

  From the above results, in addition to white turbidity at pH 4.5 or less, pranoprofen has a particular problem that it is particularly easily adsorbed to zwitterionic SCL among SCL. It has been clarified that by allowing the chondroitin sulfate sodium salt to coexist and setting the pH to 5.5 or more, it is possible to exhibit a clear appearance and to effectively suppress the adsorption to the zwitterionic SCL. .

Test example 2
A test solution was prepared by mixing each component shown in Table 2 by a conventional method. The appearance of each test solution obtained was observed and the presence or absence of white turbidity was evaluated by measuring the absorbance at a turbidity of 660 nm. Further, with respect to each of the obtained test solutions, the amount of pranoprofen adsorbed on zwitterionic SCL (lens 1 used in Test Example 1) was measured in the same manner as in Test Example 1.

  The obtained results are shown in Table 2. As a result, since all of the test solutions of Comparative Example 3, Example 3 and 6-9 were set to pH 7.7, pranoprofen did not become cloudy and exhibited a clear appearance property. In addition, in the test solutions containing pranoprofen and sodium chondroitin sulfate (Examples 3 and 6-9), the adsorption of pranoprofen to zwitterionic SCL was suppressed, but the concentration of sodium chondroitin sulfate was low. In the case of 0.05-1 w / v% (Examples 3 and 6-8), in particular in the case of 0.05-0.5 w / v% (Examples 3 and 6-7), The effect of suppressing the adsorption of pranoprofen was remarkable.

Test example 3
A test solution was prepared by mixing each component shown in Table 3 by a conventional method. The appearance of each test solution obtained was observed and the presence or absence of white turbidity was evaluated by measuring the absorbance at a turbidity of 660 nm. Further, for each of the obtained test solutions, in the same manner as in Test Example 1, to the zwitterionic SCL (the lens 1 used in Test Example 1) and the anionic SCL (the lens 2 used in Test Example 1). The amount of adsorbed pranoprofen was measured.

  The obtained results are shown in Table 3. As is apparent from Table 3, even if other glycosaminoglycans or amino acids (sodium hyaluronate and potassium L-aspartate) are used in place of chondroitin sulfate sodium, a plano to zwitterionic SCL is obtained. The adsorption amount of prophene could not be reduced sufficiently. That is, from this test result, the suppression of adsorption of pranoprofen and / or its salt to zwitterionic SCL is to select chondroitin sulfate and / or its salt as a component and set to pH 5.5 or higher. It became clear that this was a peculiar effect recognized by.

Claims (9)

  Containing pranoprofen and / or a pharmaceutically acceptable salt thereof, chondroitin sulfate and / or a pharmaceutically acceptable salt thereof, and having a pH of 5.5 or more, An ophthalmic composition for zwitterionic soft contact lenses.   The ophthalmic composition for zwitterionic soft contact lenses according to claim 1, wherein the chondroitin sulfate and / or a pharmaceutically acceptable salt thereof is sodium chondroitin sulfate.   The ophthalmic composition for zwitterionic soft contact lenses according to claim 1 or 2, wherein chondroitin sulfate and / or a pharmaceutically acceptable salt thereof is contained in an amount of 0.05 to 3 w / v%.   The ophthalmic composition for a zwitterionic soft contact lens according to any one of claims 1 to 3, wherein the pH is 5.5 to 9.   The ophthalmic composition for zwitterionic soft contact lenses according to any one of claims 1 to 4, wherein pranoprofen and / or a pharmaceutically acceptable salt thereof is contained in an amount of 0.001 to 0.5 w / v%. object.   The ophthalmic composition for zwitterionic soft contact lenses according to any one of claims 1 to 5, which is an eye drop for zwitterionic soft contact lenses.   In an ophthalmic composition for zwitterionic soft contact lenses containing pranoprofen and / or a pharmaceutically acceptable salt thereof, chondroitin sulfate and / or a pharmaceutically acceptable salt thereof are blended, and the pH is adjusted. A method for suppressing adsorption of pranoprofen and / or a pharmaceutically acceptable salt thereof to a zwitterionic soft contact lens, which is adjusted to 5.5 or more.   Zwitterionicity of a liquid preparation containing pranoprofen and / or a pharmaceutically acceptable salt thereof and chondroitin sulfate and / or a pharmaceutically acceptable salt thereof and having a pH of 5.5 or more Use for the manufacture of an ophthalmic composition for soft contact lenses. A solution containing pranoprofen and / or a pharmaceutically acceptable salt thereof and chondroitin sulfate and / or a pharmaceutically acceptable salt thereof and having a pH of 5.5 or higher is zwitterionic. A method for suppressing adsorption of pranoprofen and / or a pharmaceutically acceptable salt thereof to a zwitterionic soft contact lens, comprising a step of contacting the soft contact lens (except for a method for treating humans) .