JP2008024701A - Composition for soft contact lens comprising alginic acid or salt thereof - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition for an SCL (soft contact lens) having suppressed adsorption of alginic acid and/or a salt thereof for the SCL. <P>SOLUTION: The composition for the SCL is obtained by combining and formulating (A) the alginic acid and/or the salt thereof with (B) at least one selected from the group consisting of aspartic acid, aminoethylsulfonic acid, chondroitin sulfate, hyaluronic acid and a salt thereof. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a composition for SCL in which adsorption of alginic acid and / or a salt thereof to a soft contact lens (hereinafter referred to as “SCL”) is suppressed. Furthermore, this invention relates to the method of suppressing adsorption | suction of alginic acid to SCL.

  SCL is made of a material having a high moisture content and flexibility, and has a widespread use because it has less foreign material feeling than hard contact lenses. With the expansion of SCL users, the formulation of SCL compositions (eye drops or eyewashes that can be used while wearing SCL, SCL wearing solutions, SCL care agents, etc.) has been energetically studied. .

Alginic acid, on the other hand, has an action of gelation (high viscosity) by being partially cross-linked by a divalent or higher cation such as Ca ²⁺ ion, and should be a component that can be used in the ophthalmic field. It is already known (see, for example, Patent Document 1). When an ophthalmic solution containing alginic acid is applied to the eye, Ca ²⁺ ions present in the ocular mucosa come into contact with the alginic acid, causing the ophthalmic solution to gel (high viscosity) on the ocular mucosa. It has also been found useful for enhancing the retention of the eye drops and maintaining the effect of the active ingredient. Furthermore, it has been reported that alginic acid has an antiallergic action (see Patent Document 2). Therefore, according to the composition for SCL containing alginic acid or a salt thereof, a useful effect based on alginic acid is expected, but the influence of alginic acid on SCL has not been studied so far.

  In modern society, the number of people suffering from allergic symptoms is increasing, and the degree of the symptoms is getting worse. Against this background, allergy of SCL wearers has become a problem in conjunction with the recent spread of SCL. Therefore, from the viewpoint of antiallergic action, there is a demand for the development of a prescription that exhibits better antiallergic action in the SCL composition containing alginic acid.

On the other hand, components such as aspartic acid and aminoethyl sulfonic acid have a fatigue eye recovery action and are used in the ophthalmic field. Components such as chondroitin sulfate and hyaluronic acid are also used in the ophthalmic field for the purpose of adding moisturizing action. However, it is not known at all how these components affect the adsorption of alginic acid to SCL and whether it can affect the increase or decrease of the antiallergic effect of alginic acid.
JP 2002-332248 A JP-A-9-208475

  The inventors of the present invention conducted research on the composition for SCL containing alginic acid, and as a result, confirmed that there was a concern about the adsorption to SCL in the composition for SCL which was simply blended with alginic acid. In particular, when contact lens fitting (compatibility between the contact lens design and the user's cornea base curve) is poor, the adsorption of alginic acid to SCL may cause foreign objects and discomfort when using SCL. Therefore, in order to incorporate alginic acid into the SCL composition, it is important to avoid adsorption of alginic acid. The mechanism of adsorption of alginic acid on SCL has not been fully elucidated, and a limited interpretation is not desired. However, alginic acid adsorbs other components in SCL. Two cases are estimated: when adsorbing and adsorbing alginic acid directly on SCL. Specifically, in the former case of adsorbing alginic acid, it is considered that alginic acid adsorbs based on the following mechanism: SCL adsorbs specific components such as proteins (hereinafter referred to as adsorbing components). When the SCL is worn or handled, the adsorbing components that have an opportunity to contact the SCL are adsorbed and accumulated on the SCL, mainly as tear fluid components and finger dirt. When alginic acid comes into contact with SCL on which the adsorbing component has been adsorbed in this way, alginic acid is bound to the adsorbing component by a non-covalent bond. As a result, alginic acid is adsorbed via an adsorbing component in SCL. Such adsorption of alginic acid can occur for all SCLs. On the other hand, the case of the latter adsorption of alginic acid depends largely on the type of SCL material according to the study by the present inventors, and in particular, the adsorption of alginic acid on SCL comprising a zwitterionic polymer as a constituent material. It was confirmed that the trend increased.

  Therefore, the main object of the present invention is to provide a composition for SCL in which adsorption of alginic acid and / or a salt thereof to SCL is suppressed. Another object of the present invention is to provide an SCL composition that can be suitably used for antiallergic purposes to SCL users who have a high prevalence of allergic symptoms. Furthermore, an object of the present invention is to provide a method for suppressing adsorption of alginic acid and / or a salt thereof to SCL.

  As a result of intensive studies to solve the above problems, the present inventors have found that in the composition for SCL, in addition to alginic acid and / or a salt thereof, aspartic acid, aminoethylsulfonic acid, chondroitin sulfate, hyaluronic acid, and these It has been found that by incorporating one or more selected from the group consisting of salts, adsorption of alginic acid and / or salts thereof to SCL can be suppressed. In particular, in the composition for SCL, when aspartic acid, aminoethylsulfonic acid and / or a salt thereof are mixed with alginic acid and / or a salt thereof, the antiallergic action based on the alginic acid and / or a salt thereof is drastically increased. It was also found to be enhanced. The present invention has been completed by making further improvements based on such findings.

That is, the present invention is the following contact lens composition:
Item 1. A soft contact lens composition comprising the following components (A) and (B):
(A) Alginic acid and / or salt thereof,
(B) At least one selected from the group consisting of aspartic acid, aminoethylsulfonic acid, chondroitin sulfate, hyaluronic acid, and salts thereof.
Item 2. Item 2. The composition for soft contact lenses according to Item 1, wherein the component (B) is contained at a ratio of 1 to 50,000 parts by weight with respect to 100 parts by weight of the component (A).
Item 3. Item 3. The soft contact lens composition according to Item 1 or 2, which is an eye drop.
Item 4. Item 4. Soft contact lens classification: The soft contact lens composition according to any one of Items 1 to 3, which is for a soft contact lens belonging to Group IV.
Item 5. Item 5. The soft contact lens composition according to any one of Items 1 to 4, which is used for a zwitterionic soft contact lens.
Item 6. Item 6. The soft contact lens composition according to any one of Items 1 to 5, wherein the M / G ratio of alginic acid is 0.3 to 4.0.

Furthermore, the present invention is a method listed below:
Item 7. Item 7. A method for suppressing adsorption of alginic acid and / or a salt thereof to a soft contact lens, comprising contacting the soft contact lens with the composition for soft contact lens according to any one of Items 1 to 6.
Item 8. A method for imparting an SCL composition with an action of suppressing adsorption of alginic acid and / or a salt thereof to SCL, comprising (A) a composition for SCL containing alginic acid and / or a salt thereof, (B) asparagine A method comprising blending at least one selected from the group consisting of acids, aminoethylsulfonic acid, chondroitin sulfate, hyaluronic acid, and salts thereof.
Item 9. A method for enhancing the antiallergic action of alginic acid and / or a salt thereof in a composition for SCL, comprising (A) a composition for SCL containing alginic acid and / or a salt thereof, (B ′) aspartic acid, aminoethyl A method for enhancing antiallergic action, comprising blending at least one selected from the group consisting of sulfonic acids and salts thereof.

And still further, the present invention is a hard contact lens composition described below:
Item 10. A hard contact lens composition comprising the following components (A) and (B):
(A) Alginic acid and / or salt thereof,
(B) At least one selected from the group consisting of aspartic acid, aminoethylsulfonic acid, chondroitin sulfate, hyaluronic acid, and salts thereof.
Item 11. Item 11. The hard contact lens composition according to Item 10, which is used for an oxygen-permeable hard contact lens.

  According to the composition for SCL of the present invention, adsorption of alginic acid and / or a salt thereof to SCL is suppressed by aspartic acid, aminoethylsulfonic acid, chondroitin sulfate, hyaluronic acid, and / or a salt thereof, thereby , The wearing feeling of SCL is improved, and the foreign body feeling and discomfort during use are improved. Furthermore, according to the composition for SCL of the present invention, the same effect can be expected even when protein soil or the like is adsorbed on the SCL.

Further, alginic acid and / or a salt thereof contained in the composition for SCL of the present invention has a property of gelling upon contact with Ca ²⁺ ions present in the ocular mucosa when applied to the ocular mucosa. . Therefore, according to the SCL composition of the present invention, aspartic acid, aminoethylsulfonic acid, chondroitin sulfate, hyaluronic acid, and / or their salts are prolonged in the ocular mucosa by the gelling action of alginic acid and / or its salt. It can be retained for a long time, and the useful action based on these components can be enjoyed more effectively.

  Further, when the composition for SCL of the present invention contains aspartic acid, aminoethylsulfonic acid and / or a salt thereof together with alginic acid and / or a salt thereof, an antiallergic action based on the alginic acid and / or a salt thereof. Therefore, the composition for SCL is particularly suitable for SCL users suffering from allergic symptoms.

  Moreover, according to the method for suppressing adsorption of alginic acid and / or a salt thereof of the present invention, it is possible to suppress the adsorption of alginic acid and / or a salt thereof to SCL by a simple method. Therefore, the method of the present invention is useful for effectively expressing an action based on alginic acid and / or a salt thereof in, for example, eye drops, eye washing, or SCL care of SCL users.

(I) Composition for SCL The composition for SCL of the present invention contains (A) alginic acid and / or a salt thereof (in this specification, sometimes simply referred to as component (A)).

  Alginic acid is a polysaccharide composed of mannuronic acid (hereinafter sometimes simply referred to as “M”) and guluronic acid (hereinafter sometimes simply denoted as “G”). A block copolymer in which a polymer fraction (MM fraction), a homopolymer fraction of guluronic acid (GG fraction), and a fraction in which mannuronic acid and guluronic acid are randomly arranged (MG fraction) are arbitrarily combined. is there.

  In the alginic acid used in the present invention, the constituent ratio (M / G ratio; molar ratio) of mannuronic acid to guluronic acid is not particularly limited. For example, the M / G ratio is in the range of 0.4 to 4.0. What is included in is widely used. The smaller the M / G ratio, the easier the gelation of the composition tends to start. From the viewpoint of improving the retention at the application site of other pharmacologically active ingredients to be blended, the M / G ratio is 2. It is desirable that it is 5 or less, preferably 2.0 or less, more preferably 1.6 or less. In particular, the M / G ratio is preferably 0.4 to 2.0, more preferably 0.5 to 1.6, and particularly preferably 1.0 to 1.6. desirable. In the present invention, the M / G ratio is a value calculated by fractionating alginic acid decomposed in block units and quantifying each, and specifically, A. Haug et al., Carbohyd. Res. 32 (1974), p.217-225.

  In the alginic acid used in the present invention, the ratio of the MM fraction, the GG fraction, and the MG fraction is not particularly limited, and can be appropriately selected according to the use and shape of the SCL composition.

  Moreover, the alginic acid used in the present invention can be suitably used from a low molecular weight to a high molecular weight.

  Furthermore, the salt of alginic acid is not particularly limited as long as it is pharmacologically or physiologically acceptable. Specific examples of the alginic acid salt include sodium salt, potassium salt, triethanolamine salt, ammonium salt and the like. These alginic acid salts may be used alone or in any combination of two or more.

  In the composition for SCL of the present invention, one kind selected from these alginic acids and salts thereof may be used alone, or two or more kinds may be used in any combination. In particular, alginic acid, sodium alginate, and potassium alginate are water-soluble and are preferably used in the present invention.

  The mixing ratio of the component (A) in the composition for SCL of the present invention is not particularly limited, and can be appropriately set according to the type of the component (A), the use and form of the composition, and the like. As an example of the blending ratio of the component (A), the total amount of the component (A) is 0.005 to 0.5% by weight, preferably 0.01 to 0.25% by weight, based on the total amount of the composition in the SCL composition; For example, if the SCL composition is an eye drop, it is more preferably 0.02 to 0.1% by weight, particularly preferably 0.05 to 0.1% by weight; for example, if the SCL composition is an eye wash, more preferably 0.01 to 0.1% by weight. Particularly preferred is a ratio of 0.01 to 0.05% by weight. When satisfying such a blending ratio, an antiallergic action can be effectively expressed together with the gelling action of the component (A).

  The SCL composition of the present invention comprises one or two or more components (present) among (B) aspartic acid, aminoethylsulfonic acid, chondroitin sulfate, hyaluronic acid, and salts thereof together with the component (A). In the specification, it may be simply expressed as (B) component). By containing the component (B), it is possible to effectively suppress the adsorption of the component (A) to the SCL and effectively express the useful action of the component (A).

Among the components (B), aspartic acid and salts thereof are known compounds as amino acids having an effect on recovery from eye fatigue. Examples of the salt of aspartic acid include salts with alkali metals such as sodium and potassium; salts with alkaline earth metals such as calcium and magnesium. Preferably, it is potassium aspartate.

  In addition, among the above component (B), aminoethylsulfonic acid is a known compound called alias taurine or 2-aminoethanesulfonic acid, and is also known to promote metabolism and have an eye fatigue recovery effect. ing.

  Among the components (B), chondroitin sulfate and salts thereof are known high molecular compounds as a kind of mucopolysaccharide that exhibits a moisturizing action in the ocular mucosa and the like. The chondroitin sulfate and salts thereof used in the present invention are not particularly limited in terms of their origin. For example, they may be obtained from animals such as salmon or from microorganisms. May be. The average molecular weight of the chondroitin sulfate used in the present invention is not particularly limited, but is, for example, 50,000 to 500,000, preferably 50,000 to 200,000, more preferably 50,000 to 100,000, particularly Preferably, it is 0.5 to 50,000, more particularly preferably 10,000 to 40,000, and most preferably 15,000 to 35,000.

  Specific examples of the salt of chondroitin sulfate include salts with alkali metals such as sodium and potassium; salts with alkaline earth metals such as calcium and magnesium; salts with other metals such as aluminum and the like. The Preferred is an alkali metal salt of chondroitin sulfate, and more preferred is sodium chondroitin sulfate.

  As such chondroitin sulfate or a salt thereof, a commercially available product can be used. For example, sodium chondroitin sulfate sold by Seikagaku Corporation, sodium chondroitin sulfate sold by Maruha Corporation, or the like can be used.

Of the above component (B), hyaluronic acid and salts thereof are known high molecular compounds as a kind of mucopolysaccharide that exhibits a moisturizing action in the ocular mucosa and the like. The hyaluronic acid and salts thereof used in the present invention are not particularly limited in terms of their origin, and may be obtained from, for example, chicken crowns or derived from microorganisms. Although it does not restrict | limit especially as an average molecular weight of the hyaluronic acid used for this invention, For example, 5-5 million, Preferably it is 500-4 million, More preferably, it is 600,000-2,500,000, Especially preferably, it is 800,000-2 million What is in the range is exemplified. Here, the average molecular weight of hyaluronic acid in this specification means the viscosity average molecular weight. The viscosity average molecular weight can be determined by a known measurement method. Specifically, hyaluronic acid and / or a salt thereof (dried product) is dissolved in a 0.2 M sodium chloride solution to determine the intrinsic viscosity (η) at 30 ° C., and the Laurent equation (η (intrinsic viscosity) = 0. Based on 00003 × Mv (viscosity average molecular weight) ^0.78 ), the viscosity average molecular weight is calculated. The intrinsic viscosity (η) is measured according to the 14th revised Japanese Pharmacopoeia general test method and viscosity measurement method (capillary viscometer method).

  Examples of the salt of hyaluronic acid include salts with alkali metals such as sodium and potassium; salts with alkaline earth metals such as calcium and magnesium; salts with metals such as aluminum and the like. Preferred examples of such a salt state include a sodium salt and a potassium salt. Moreover, it is preferable to use hyaluronic acid in a salt state as compared with hyaluronic acid because it is more stable.

  A commercially available thing can be used for the hyaluronic acid and its salt used for this invention. Representative examples of such commercially available products are “Bio Sodium Hyaluronate” (manufactured by Shiseido Co., Ltd.), “Hyaluron Sun HA-QA” (manufactured by Kewpie Co., Ltd.), and “Hyaluron Sun HA-AM” (trade name). Commercial products such as Kewpie Co., Ltd.) can be exemplified.

  In addition, among the components (B), at least one selected from the group consisting of aspartic acid, aminoethylsulfonic acid, and salts thereof (in this specification, it may be simply expressed as component (B ′)) Is advantageous in that the antiallergic action of the component (A) can be dramatically enhanced, and when these (B ′) components are employed, the composition for SCL of the present invention is It is also useful as an SCL composition (anti-allergy SCL composition) that also has an antiallergic effect.

  These components (B) may be used alone or in combination of two or more. By adopting two or more components as component (B), the effects of the present invention may be further improved.

  In the composition for SCL of the present invention, from the viewpoint of more effectively suppressing the adsorption of the component (A) to the SCL, the component (B) with respect to 100 parts by weight of the total amount of the component (A) Is preferably 1 to 50000 parts by weight, preferably 10 to 10000 parts by weight, more preferably 10 to 5000 parts by weight, and still more preferably 10 to 2000 parts by weight. In particular, when the component (B) uses aspartic acid, aminoethylsulfonic acid, chondroitin sulfate, and / or a salt thereof, the total amount of the component (A) is 100 parts by weight with respect to ( It is particularly preferable that the component B) satisfies a ratio of 100 to 2000 parts by weight in total. Further, when the component (B) uses hyaluronic acid and / or a salt thereof, the total amount of the component (A) is 100 to 600 parts by weight with respect to the total amount of the component (A) 100 parts by weight. It is particularly preferable to satisfy the ratio of parts.

In addition, the blending ratio of the component (B) in the SCL composition of the present invention is not particularly limited, and the type of component (A) and component (B) used, the component (A) and (B) It can set suitably according to the ratio of a component, the use, form, etc. of this composition. As an example of the blending ratio of the component (B), in the SCL composition, the total amount of the component (B) is 0.0001 to 5% by weight, preferably 0.001 to the total amount of the composition. A proportion of 3% by weight, more preferably 0.001 to 2.0% by weight, particularly preferably 0.001 to 1% by weight is exemplified. More specifically, the following ranges are illustrated as a mixture ratio of (B) component.
When component (B) is aspartic acid and / or a salt thereof: These are total amounts, usually 0.001 to 5.0% by weight, preferably 0.01 to 2.0% by weight; for example, a composition for SCL is instilled If it is an agent, it is more preferably 0.1 to 2.0% by weight, particularly preferably 0.2 to 1.0% by weight; for example, if the SCL composition is an eyewash, it is more preferably 0.01 to 0.2% by weight, particularly preferably 0.05 to 0.1% by weight.
When component (B) is aminoethylsulfonic acid: usually 0.001 to 3.0% by weight, preferably 0.01 to 1.0% by weight; for example, if the SCL composition is an eye drop, it is more preferably 0.1 to 1.0% by weight, particularly preferably 0.2 to 1.0% by weight; for example, if the SCL composition is an eye wash, more preferably 0.01 to 0.1% by weight, particularly preferably Is 0.02 to 0.1% by weight.
When component (B) is chondroitin sulfate and / or a salt thereof: These are total amounts, usually 0.0005 to 5.0% by weight, preferably 0.005 to 3.0% by weight; for example, a composition for SCL is instilled If it is an agent, it is more preferably 0.05 to 0.5% by weight, particularly preferably 0.1 to 0.5% by weight; for example, if the SCL composition is an eyewash, more preferably 0.005 to 0.05% by weight, particularly preferably 0.01 to 0.05% by weight.
When component (B) is hyaluronic acid and / or a salt thereof: These are total amounts, usually 0.0001 to 2.0% by weight, preferably 0.001 to 0.3% by weight; for example, a composition for SCL is instilled If it is an agent, it is more preferably 0.01 to 0.3% by weight, particularly preferably 0.01 to 0.1% by weight; for example, if the SCL composition is an eye wash, more preferably 0.001 to 0.1% by weight, particularly preferably 0.001 to 0.01% by weight.

  Moreover, you may mix | blend a buffering agent with the composition for SCL of this invention further. By blending a buffering agent, the suppression of adsorption of the component (A) to SCL may be more effectively expressed. The buffer that can be incorporated into the SCL composition of the present invention is not particularly limited as long as it is pharmacologically or physiologically acceptable. Examples of such buffers include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, epsilon-aminocaproic acid, and the like. These buffering agents may be used in combination. Preferred buffering agents are borate buffer, phosphate buffer, carbonate buffer and citrate buffer. Particularly preferred buffering agents are borate buffer, citrate buffer or phosphate buffer. Examples of the borate buffer include borates such as alkali metal borate and alkaline earth metal borate. Examples of the phosphate buffer include phosphates such as alkali metal phosphates and alkaline earth metal phosphates. Examples of the citrate buffer include alkali metal citrate and alkaline earth metal citrate. Moreover, you may use the borate or the hydrate of a phosphate as a borate buffer or a phosphate buffer. As more specific examples, boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.), phosphoric acid or a salt thereof (disodium hydrogen phosphate, dihydrogen phosphate) Sodium, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate), carbonic acid or a salt thereof (sodium hydrogen carbonate, sodium carbonate, ammonium carbonate, potassium carbonate, Calcium carbonate, potassium hydrogen carbonate, magnesium carbonate, etc.), citric acid or a salt thereof (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.) acetic acid or a salt thereof (ammonium acetate, Potassium acetate, calcium acetate, sodium acetate, etc.) Can be illustrated. These buffering agents may be used alone or in any combination of two or more.

When a buffering agent is blended in the SCL composition of the present invention, the blending ratio of the buffering agent varies depending on the type of buffering agent used and the expected effect, and cannot be defined uniformly. For example, the ratio that the buffering agent is 0.001 to 10% by weight, preferably 0.1 to 5% by weight, with respect to the total amount of the composition. More specifically, when the ratio of the buffer in the composition is a borate buffer or a phosphate buffer, for example, 0.0001 to 10% by weight, preferably 0.01 to 5% by weight. If a carbonate buffer is used, for example 0.001 to 5% by weight, preferably 0.005 to 3% by weight; if a citrate buffer is used, for example 0.001 to 5% by weight; Preferably 0.005 to 3% by weight; if an acetate buffer is used, for example 0.001 to 5% by weight, preferably 0.005 to 3% by weight; if epsilon-aminocaproic acid is used, For example, the ratio is 0.005 to 10% by weight, preferably 0.01 to 5% by weight.

  The SCL composition of the present invention is liquid or gel, preferably liquid, and ophthalmically acceptable water, preferably purified water or ultrapure water, is used as the base material of the composition. .

  The pH of the SCL composition of the present invention is not particularly limited as long as it is within a pharmacologically or physiologically acceptable range. As an example of pH of the composition for SCL of this invention, the range used as 5-9, Preferably 5.5-8.5, More preferably 6-8 can be mentioned. Moreover, if it is in the said pH range, it is safe even if it applies to eyes and a lens, the effect of this invention can be improved further, and it is practical as an ophthalmic formulation.

  The SCL composition of the present invention can be further adjusted to an osmotic pressure ratio within a range acceptable for a living body, if necessary. The appropriate osmotic pressure ratio varies depending on the use and form of the composition, but is usually 0.2 to 1.8, preferably 0.3 to 1.7, more preferably 0.4 to 1.6, more preferably 0.5 to 1.5, particularly preferably 0.6 to 1.4, Especially preferably, it is 1.0-1.2. If it is in the range of this osmotic pressure, the effect of the present invention can be improved further.

  In the composition for SCL of the present invention, the osmotic pressure ratio is the ratio of the osmotic pressure of the sample to the osmotic pressure of the 0.9 w / v% aqueous sodium chloride solution based on the 14th revised Japanese pharmacopoeia, and the osmotic pressure is described in the Japanese pharmacopoeia. Measured according to the osmotic pressure measurement method (freezing point depression method). The standard solution for measuring the osmotic pressure ratio was sodium chloride (Japanese Pharmacopoeia standard reagent) dried at 500 to 650 ° C. for 40 to 50 minutes, then allowed to cool in a desiccator (silica gel), and 0.900 g was accurately weighed. Dissolve in purified water to make exactly 100 mL, or use a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution).

  The pH and osmotic pressure ratio can be adjusted by a method known in the art using inorganic salts and polyhydric alcohols, sugar alcohols, saccharides, and the like.

  The composition for SCL of the present invention can contain various components (including pharmacologically active components and physiologically active components) in combination with the above components as long as the effects of the present invention are not hindered. The kind of such an ingredient is not particularly limited, and examples thereof include active ingredients in various medicines described in the over-the-counter drug manufacturing (import) approval standard 2000 version (supervised by the Pharmaceutical Affairs Research Committee). Specific examples of components used in ophthalmic drugs include the following components.

  Epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, tetrahydrozoline hydrochloride, naphazoline hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride, naphazoline nitrate, neostigmine methyl sulfate, zinc sulfate, zinc lactate, allantoin, epsilon-aminocaproic acid, lysozyme chloride, sodium azulene sulfonate, glycyrrhizin Dipotassium acid, berberine chloride, berberine sulfate, diphenhydramine hydrochloride, chlorpheniramine maleate, retinol acetate, retinol palmitate, pyridoxine hydrochloride, sodium flavin adenine dinucleotide, cyanocobalamin, panthenol, calcium pantothenate, sodium pantothenate, tocopherol acetate , Sulfamethoxazole, sulfisoxazole, sulfamethoxax Lumpur sodium, sulphates iso thymidine sodium, glucose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, polyvinyl alcohol (completely or partially saponified products), polyvinyl pyrrolidone.

  Furthermore, in order to prepare the SCL composition of the present invention in various desired forms, various components and additives are appropriately selected according to conventional methods within a range not impairing the effects of the present invention, and one or more of them are selected. It can mix | blend together. Examples of these components or additives include various additives described in Pharmaceutical Additives Encyclopedia 2005 (edited by Japan Pharmaceutical Additives Association). Typical additives include the following additives.

  Macrogol, poloxamer, poloxamine, polysorbate 80, POE (60) hydrogenated castor oil, alkyldiaminoethylglycine, benzalkonium chloride, parabens, potassium sorbate, polyhexamethylene biguanide or its hydrochloride, potassium chloride, sodium chloride, Calcium chloride, magnesium sulfate, glycerin, propylene glycol, camphor, geraniol, borneol, menthol, fennel oil, cool mint oil, spearmint oil, peppermint oil, bergamot oil, eucalyptus oil, rose oil, sodium edetate, citric acid, trometamol, etc. .

  If the composition for SCL of this invention is used so that it may contact SCL, the form and application will not be restrict | limited. For example, eye drops for SCL (eye drops that can be used while wearing SCL), eye drops for SCL (eye wash that can be used while wearing SCL), SCL wearing liquid, liquid for SCL care (SCL disinfectant, SCL Storage solution, SCL cleaning solution, SCL cleaning storage solution, and the like. From the viewpoints of ease of use, action imparted by alginic acid (improving retention), and the like, eye drops for SCL, eyewashes for SCL, and SCL mounting solutions are preferred.

  Further, the method for using the SCL composition of the present invention is not particularly limited as long as it is a known method having a step of bringing the SCL composition into contact with SCL. For example, in the case of eye drops, an appropriate amount of the agent may be instilled before, at the time of wearing, or during wearing. In the case of an eye wash, an appropriate amount of the agent may be used for eye washing before, at the time of wearing, or during wearing (while wearing the SCL). In addition, when the composition for SCL of this invention is an eye drop or an eye wash, it can be used for the purpose of eye drop and eye wash not only when wearing SCL but also when wearing it. Further, in the case of SCL mounting liquid, it is used by bringing SCL into contact with an appropriate amount of the liquid when SCL is mounted. Furthermore, in the case of a liquid for SCL care, it is used by immersing SCL in an appropriate amount of the agent or by rubbing it in contact with the agent.

  The SCL composition of the present invention can be used for all types of SCL. Alginic acid and / or its salt, especially in the highly hydrous ionic SCL (soft contact lens classification: Group IV), which easily adsorbs proteins, becomes a lens of component (A) when the lens adsorbs protein dirt. There is a tendency that the adsorption of becomes remarkable. In addition, zwitterionic SCL tends to be easily adsorbed to the lens material itself. On the other hand, according to the present invention, it is possible to exert an effective adsorption suppressing effect on high water content ionic SCL (soft contact lens classification: group IV) and zwitterionic SCL. For these reasons, one embodiment of the SCL composition of the present invention is preferably exemplified by a high water content ionic SCL (soft contact lens classification: Group IV) or a zwitterionic SCL. Is done. In the present specification, zwitterionic SCL means SCL prepared using a zwitterionic polymer (for example, a polymer having a quaternary ammonium group and a carboxyl group) as a raw material. In addition, in this specification, the soft contact lens classification means the Pharmaceutical Examination No. 645 dated March 31, 1999 (Ministry of Health, Labor and Welfare) SCL classification based on “How to classify soft contact lenses” defined in “Handling of Materials to be Attached when Applying for Manufacturing (Import) Approval of Agents”. The common property is that the ratio is 50% or more and the mole% of the monomer having an anion among the constituent monomers of the raw material polymer is 1% or more.

The composition for SCL of the present invention is produced according to a known method. For example, the components (A) and (B) described above are added to an aqueous solvent such as purified water and physiological saline, and the other components are added to a desired concentration as necessary, and prepared according to a conventional method. That's fine.

(II) Method for inhibiting adsorption of alginic acid and / or salt thereof to SCL As described above , adsorption of alginic acid and / or salt thereof to SCL can be inhibited by using the component (B). Therefore, the present invention further provides a method for inhibiting adsorption of alginic acid and / or a salt thereof to SCL, wherein the SCL is contacted with the SCL composition described in (I) above (however, treatment of the human body). (Excluding methods applicable to the method).

  In the adsorption suppression method, the contact between the SCL composition (I) and the SCL may be performed according to a normal use method according to the form and application of the composition to be used. Specifically, the method of making it contact with SCL can be mentioned by using this SCL composition according to the usage method of the SCL composition as described in said (I).

  Furthermore, the present invention is a method for imparting an action of inhibiting the adsorption of alginic acid and / or a salt thereof to SCL from another viewpoint to the composition for SCL, the composition for SCL containing the component (A) above There is also provided a method for imparting an SCL adsorption-inhibiting action, which comprises blending the component (B) with a product.

  In these methods, the types and blending ratios of component (A) and component (B), other blending components, and the like are as described in the column for the SCL composition in (I) above.

(III) Method for enhancing antiallergic action of alginic acid and / or salt thereof Further, as described above, the antiallergic action of alginic acid and / or salt thereof can be enhanced by coexisting the component (B ′). it can. Therefore, the present invention further relates to a method for enhancing the antiallergic action of alginic acid and / or a salt thereof in the SCL composition, wherein the SCL composition containing the component (A) contains the (B ′) There is also provided a method for enhancing antiallergic action, which comprises blending ingredients. In this method, the types and blending ratios of the component (A) and the component (B ′), other blending components, and the like are as described in the column for the SCL composition in (I) above.

(IV) Composition for Hard Contact Lens A hard contact lens (hereinafter referred to as HCL) may adsorb components such as proteins contained in tear fluid components and finger dirt during wearing and handling. When alginic acid and / or a salt thereof come into contact with HCL to which the protein is adsorbed in this way, the protein and alginic acid are bound by a non-covalent bond, and as a result, alginic acid is adsorbed to HCL through the protein. Adsorption of alginic acid thus generated onto HCL can be suppressed by allowing the above component (B) to coexist with alginic acid.

  Based on such findings, the present invention further provides an HCL composition containing the components (A) and (B) as an HCL composition in which adsorption of alginic acid and / or a salt thereof to HCL is suppressed. A composition is provided. In the HCL composition, the component (A), the component (B), other blending components, the blending ratio of each blending component, the use and form of the HCL composition, the method of using the HCL composition, etc. The same as described in the column of the composition for SCL (I).

  Moreover, the said composition for HCL is applicable to all types of HCL. Among these, oxygen-permeable HCL is known to be easily contaminated with dirt, and oxygen-permeable HCL is a suitable application target HCL of the HCL composition.

  Hereinafter, the present invention will be described in detail based on test examples, examples, and the like, but the present invention is not limited thereto. The alginic acid used below is derived from Lessonia nigrescens having a M / G ratio of 1.0 to 1.6; sodium hyaluronate has an average molecular weight of 1.1 million to 1.6 million; and sodium chondroitin sulfate is The average molecular weight is 10,000 to 20,000.

Test Example 1 Adsorption inhibition evaluation test of alginic acid on SCL-1
In order to examine the effects of potassium aspartate, aminoethylsulfonic acid, sodium chondroitin sulfate, and sodium hyaluronate on the adsorption of alginic acid to SCL, the following tests were conducted.
<Test material>
The compositions for SCL shown in Table 1 below (Example 1-4 and Comparative Example 1) were prepared according to a conventional method. In this test, SCL is trade name “Seed 2 Week Pure” (Zwitterionic; Seed, Inc .; water content; constituent monomer: hydroxyethyl methacrylate (HEMA), quaternary ammonium group-containing methacrylate compound, carboxyl group. Containing methacrylate compounds, methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA); soft contact lens classification: Group IV) were used.

<Test method>
Japanese Pharmacopoeia Each SCL was immersed in 5 mL of physiological saline and left at room temperature (about 25 ° C.) for about 24 hours. Subsequently, SCL was extracted from the physiological saline and lightly wiped off moisture. Dispense 4 mL of the SCL composition of Example 1-4 and Comparative Example 1 into clear glass vials with high sealing properties, and immerse the two SCLs obtained above in each SCL composition. Then, after shaking at 34 ° C. at a shaking speed of 120 times / minute for about 72 hours, SCL was extracted. Next, the concentration of each alginic acid remaining in each SCL composition after the SCL immersion treatment (hereinafter referred to as a post-test Alg concentration) was measured using high performance liquid chromatography. In addition, as a blank, except having not immersed SCL, the process similar to the above was performed and the density | concentration of alginic acid remaining in the composition for SCL in the case of not immersing SCL (henceforth a blank Alg density | concentration) was measured. .

  From the measured concentration of alginic acid, the amount of alginic acid adsorbed (μg / SCL 1 sheet) was calculated according to the following formula, and the adsorption inhibition rate (%) of alginic acid was further determined.

The results are also shown in Table 1. In the SCL composition of Comparative Example 1, alginic acid was adsorbed on SCL. On the other hand, in the composition for SCL of Example 1-4 which mix | blended potassium aspartate, aminoethylsulfonic acid, sodium chondroitin sulfate, and sodium hyaluronate, the adsorption amount to SCL of alginic acid reduced significantly. It was. In particular, the effect of suppressing the adsorption of alginic acid to SCL was remarkably observed when potassium aspartate, aminoethylsulfonic acid, or sodium hyaluronate was added.

Test Example 2 Adsorption Inhibition Evaluation Test 2 for Alginic Acid on SCL-2
Using the composition for SCL (Example 5-12 and Comparative Example 1) shown in Table 2 below, the effect of suppressing the adsorption of alginic acid on SCL was evaluated in the same manner as in Test Example 1.

  As a result, it was confirmed that the adsorption of alginic acid to SCL was remarkably suppressed in the SCL composition of Example 5-12, as in Test Example 1 above. That is, from the results of Test Example 2 and the results of Test Example 1, 100 to 2000 parts by weight of chondroitin sulfate sodium, potassium aspartate or aminoethyl sulfonic acid, or hyaluronic acid is added to 100 parts by weight of the total amount of alginic acid. It was confirmed that a good adsorption inhibition effect of alginic acid on SCL can be obtained by blending at a ratio of 10 to 600 parts by weight.

Test Example 3 Evaluation of lens wearing feeling
The following tests were conducted by 8 subjects using SCL using the eye drops (Examples 13 to 16 and Comparative Example 2) shown in Table 4, and each eye drop had a feeling of wearing SCL ( We examined the effect on the feeling of discomfort and discomfort. In addition, 4 of the subjects used the product name “Medalist Plus” (made by Bosch Lom, water content, main material: hydroxyethyl methacrylate (HEMA), soft contact lens classification: group I) as the SCL, and the other 4 subjects. The name used was the trade name “2 Week Accuview” (manufactured by Johnson & Johnson, water-containing, main material: copolymer of hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA)) as SCL.

  Specifically, each test subject was put on for 1 week according to the usage of each SCL, and after having put dirt such as protein adsorbed on the SCL, eye drops were applied to the eye wearing the SCL 5-6 times a day. Instilled at a frequency of 1 week. The results of the evaluation of the feeling of feeling and the overall evaluation of the feeling of wearing at the time of the last instillation on the last day were scored according to the evaluation criteria shown in Table 3 below.

  The obtained results are also shown in Table 4. As a result, it is clear that the eye drop of Example 13-16 has improved feeling of feeling and discomfort and a better wearing feeling than the case of using the eye drop of Comparative Example 2. It became. In particular, in the eye drops of Examples 13-16, a better wearing feeling was obtained in subjects using SCL belonging to Group IV.

Test Example 4 Evaluation test of antiallergic effect (histamine release inhibitory effect) Rat anti-basic cell line (RBL-2H3; distributed by Human Science Research Resource Bank) to a concentration of 1.5 × 10 ⁵ cells / ml Was suspended in Dulbecco's modified Eagle medium (manufactured by Invitrogen) (hereinafter referred to as growth medium) containing fetal bovine serum (10% by volume). This cell suspension was seeded on a 96-well microtiter plate (manufactured by Corning) at 0.2 ml per well and cultured for 24 hours at 37 ° C. under 5% CO ₂ . Next, the culture medium was removed by aspiration, and 1 ml of growth medium in which the test substance was dissolved to the concentration shown in Table 5 was added, and incubated for 2 hours at 37 ° C. under 5% CO ₂ . Thereafter, calcium ionophore A23187 (manufactured by Sigma-Aldrich) was added to each well so as to be 50 μM, and further incubated at 37 ° C. under 5% CO _{2 for} 30 minutes. The supernatant of each well was collected, and the concentration of histamine released in the supernatant was quantified using an ELISA kit (manufactured by Oxford Biomedical Research).

  The results obtained are shown in Table 5. From this result, it was confirmed that potassium aspartate and aminoethylsulfonic acid have an action of enhancing the histamine release inhibitory action of sodium alginate.

Test Example 5 Adsorption inhibition evaluation test of alginate on SCL-3
In order to examine the effects of potassium aspartate, aminoethylsulfonic acid, sodium chondroitin sulfate, and sodium hyaluronate on the adsorption of alginic acid to SCL with protein stains, the following tests were conducted.
<Test material>
The SCL compositions (Examples 17-20 and Comparative Example 3) shown in Table 6 below were prepared according to a conventional method. In this test, the following lenses were used as SCL.
A. Product name “Medalist Plus” (manufactured by Bausch & Lombs, water content, main material: hydroxyethyl methacrylate (HEMA), soft contact lens classification: Group I),
B. Product name "2 week Accuview" (manufactured by Johnson & Johnson, water-containing, main material: copolymer of hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA))
<Test method>
Weigh 1.0 g of ovalbumin, 0.1 g of lysozyme chloride and 0.1 g of porcine stomach mucin and add 100 mL of phosphate buffer (see 15th revised Japanese Pharmacopoeia, General Test Method, phosphate buffer, pH 7.2). An artificial soil solution was prepared by dissolving to pH = 7.2, and the unused test contact lens was immersed in 5 mL of this solution and shaken at 37 ° C. for about 8 hours. Thereafter, each lens was taken out from the artificial soil solution, and excess artificial soil solution was lightly rinsed with physiological saline, followed by lightly wiping off moisture. Next, 4 mL each of the SCL compositions of Examples 17-20 and Comparative Example 3 were dispensed into clear glass vials with high sealing properties, and the two SCLs obtained above were dispensed into each SCL composition. Was immersed for about 72 hours at a rate of 120 times / minute at 34 ° C., and then SCL was extracted. Next, the concentration of each alginic acid remaining in each SCL composition after the SCL immersion treatment (post-test Alg concentration) was measured using high performance liquid chromatography. In addition, the process similar to the above was performed except not immersing SCL as a blank, and the density | concentration (blank Alg density | concentration) of the alginic acid which remains in the composition for SCL in the case of not immersing SCL was measured.

  From the measured concentration of alginic acid, the amount of alginic acid adsorbed (μg / SCL 1 sheet) was calculated according to the formula shown in the above equation 1, and the adsorption inhibition rate (%) of alginic acid was further determined.

  The results are also shown in Table 6. In the SCL composition of Comparative Example 3, alginic acid was adsorbed on SCL. On the other hand, in the composition for SCL of Examples 17-20 containing potassium aspartate, aminoethyl sulfonic acid, sodium chondroitin sulfate, or sodium hyaluronate, the effect of suppressing the adsorption of alginic acid to SCL was remarkably recognized. It was.

Formulation Example 1-65
In the formulations described in Table 7-17 below, eye drops for SCL (Prescription Examples 1-6, 13-19, 37-52, 56-58 and 61-65), eyewashes for SCL (Prescription Examples 7-12, 20-36) and SCL mounting solutions (Formulation Examples 53-55 and 59-60).

Reference Formulation Example 1-10
An eye-permeable preparation for oxygen permeable HCL (Prescription Example 1-10) was prepared according to the formulation shown in Table 18 below.

Claims (5)

A soft contact lens composition comprising the following components (A) and (B):
(A) Alginic acid and / or salt thereof,
(B) At least one selected from the group consisting of aspartic acid, aminoethylsulfonic acid, chondroitin sulfate, hyaluronic acid, and salts thereof.   The composition for soft contact lenses according to claim 1, wherein the component (B) is contained at a ratio of 1 to 50,000 parts by weight with respect to 100 parts by weight of the component (A).   The composition for soft contact lenses according to claim 1 or 2, which is an eye drop.   The composition for soft contact lenses according to any one of claims 1 to 3, which is used for zwitterionic soft contact lenses.   A method for suppressing adsorption of alginic acid and / or a salt thereof to a contact lens, comprising contacting the contact lens with the composition for soft contact lens according to any one of claims 1 to 4.