JP2019174830A - Composition for soft contact lens - Google Patents

Abstract

To provide a composition for a soft contact lens capable of inhibiting deformation of a soft contact lens caused by polysorbate 80.SOLUTION: Provided is a composition for a soft contact lens comprising polysorbate 80 and at least one kind of a refrigerant selected from a group consisting of menthol, camphor, borneol and geraniol, where polydispersity of the polysorbate 80 in the composition for a soft contact lens ranges 1.00-1.28.SELECTED DRAWING: None

Description

The present invention relates to a composition containing a cooling agent and polysorbate 80 and applied to a soft contact lens. The present invention also relates to a method for suppressing deformation of a soft contact lens caused by polysorbate 80. The present invention also relates to a method for suppressing blurring of eyes while wearing a soft contact lens with a composition containing a refreshing agent and polysorbate 80.

The development of contact lenses began with glass lenses and has been developed in various ways such as hard plastic lenses and hydrous plastic lenses. A contact lens is required to have excellent optical characteristics and biocompatibility for any purpose of use such as correction of visual acuity, treatment of eye diseases, examination, fashion, and the like. In contact lenses biocompatibility, safety and poor wear are problems. For example, when the amount of oxygen supplied to the cells of the eye decreases, the growth of corneal epithelial cells and the thickening of the cornea occur. For this reason, although it is considered that safety problems occur such as eye damage due to deterioration of fitting with a contact lens, the cause has not been elucidated. Many other problems with wearing contact lenses have been pointed out, but the causal relationship is thought to be complex, and the mechanism has not been clarified.

For this reason, contact lens materials have been developed focusing on various causal relationships, and contact lenses with various properties have been put on the market. Hard contact lenses made of hard materials and soft contact lenses made of soft materials (SCL) have become widespread. For example, silicone hydrogel contact lenses (SHCL) in which silicone is blended with hydrogel have been spreading in recent years.

In parallel with the launch of soft contact lenses having various properties, various compositions applied to soft contact lenses have been developed to enhance safety and wearing comfort. For example, an eye drop for soft contact lenses (Patent Document 1) containing a refreshing agent and a surfactant, wherein the amount of the surfactant is 10 to 100 times that of the refreshing agent. Are known. An ophthalmic solution that can be applied when wearing a contact lens, containing a nonionic surfactant selected from tranilast or a pharmacologically acceptable salt thereof, polyvinylpyrrolidone, and polyoxyethylene hydrogenated castor oil (patent) Document 2) is known. Furthermore, an ophthalmic composition for soft contact lenses containing a nonionic surfactant having an HLB of 11 or more and polyoxyethylene castor oil having an average addition mole number of ethylene oxide of 2 to 20 (Patent Document 3) It has been known.

However, the safety and wearing feeling of contact lens wearers are not sufficient, and further improvements are required.

Japanese Patent Laid-Open No. 2005-036011 JP 2011-225626 A JP 2014-015453 A

The present inventors have conducted various studies on a composition containing polysorbate 80 (polyoxyethylene (20) sorbitan monooleate), and the mechanism of action relating to deformation of the soft contact lens is that of polysorbate 80. We obtained a completely new finding that it depends on the specific properties. Conventionally, it has been known that nonionic surfactants change the size of soft contact lenses (Patent Documents 2 and 3). However, it has not been known so far that the mechanism of the influence of polysorbate 80 on the size of SCL differs depending on the characteristics of polysorbate 80, and the present inventors have found it for the first time. Moreover, there is a concern that a change in the shape of the contact lens may adversely affect the visual acuity correction power of the contact lens. Furthermore, it may cause various eye symptoms and deterioration of wearing feeling.

One aspect of the present invention has been made in view of the above circumstances, and an object thereof is to provide a soft contact lens composition capable of suppressing the deformation of the soft contact lens caused by the polysorbate 80. Another aspect of the present invention has been made in view of the above circumstances, and an object thereof is to provide a composition for a soft contact lens capable of suppressing blurring of eyes while wearing the soft contact lens.

In the embodiment of the ophthalmic composition, it has been known that the refreshing agent changes the physicochemical parameters of the contact lens (Patent Document 1). As a result of investigation, when the polydispersity of polysorbate 80 contained in the soft contact lens composition is within a specific numerical range, the composition of the lens can be further improved by adding a specific cooling agent such as menthol to the composition. It was found that deformation was suppressed. In general, polysorbates are selected and used with an index of HLB (Hydrophile-Lipophile Balance), which exhibits a balance between hydrophilicity and lipophilicity, with the expectation of effects such as emulsification, dispersion, and wetting. The polydispersity calculated by the ratio between the weight average molecular weight and the number average molecular weight is known as an index indicating the molecular weight distribution of a polymer compound or the like, but is not often used as an index of polysorbate 80. The present inventors are the first to pay attention to the correlation between the polydispersity of the polysorbate 80 and the size change (deformation) of the lens.

As a result of further studies based on these findings, the present invention has been completed.

That is, this invention provides the composition for soft contact lenses of the following aspect. Although the details of the mechanism for suppressing the deformation of the soft contact lens by setting the polydispersity of polysorbate 80 within the following range have not been clarified, the micelle structure between polysorbate 80 and the cooling agent is different due to the difference in polydispersity. It may be slightly different and may contribute to the speed of interaction with the soft contact lens matrix, which is a kind of gel containing water.

Item 1-1. A composition for soft contact lenses comprising polysorbate 80 and at least one refreshing agent selected from the group consisting of menthol, camphor, borneol and geraniol, wherein the polysorbate in the soft contact lens composition The composition for soft contact lenses whose polydispersity of 80 is 1.00-1.28. Item 1-2. Item 10. The soft contact lens composition according to Item 1-1, wherein the polydispersity of the polysorbate 80 in the soft contact lens composition is 1.00 to 1.26. Claim | item 1-3. Claim | item 1-1 or 1-2 whose content of the said polysorbate 80 in the said composition for soft contact lenses is 0.5-100 weight part with respect to 1 weight part of cooling agents. Composition for soft contact lenses. Claim | item 1-4. Item 4. The soft contact lens composition according to any one of Items 1-1 to 1-3, wherein the softening agent content in the soft contact lens composition is 0.0001 to 0.5 w / v%. . Item 1-5. The soft contact lens according to any one of Items 1-1 to 1-4, wherein the polydispersity of the polysorbate 80 in the soft contact lens composition is 15 to 2000 with respect to 1 part by weight of the cooling agent. Composition. Item 1-6. Item 6. The soft contact lens composition according to any one of Items 1-1 to 1-5, which is for a silicone hydrogel contact lens.

Moreover, this invention provides the method of suppressing a deformation | transformation of a soft contact lens of the aspect hung up below. Item 2-1. The polysorbate 80 comprising a step of contacting a soft contact lens with a composition for soft contact lens containing polysorbate 80 and at least one cooling agent selected from the group consisting of menthol, camphor, borneol and geraniol. A method for suppressing deformation of a soft contact lens caused by contact with the soft contact lens, wherein the polydispersity of the polysorbate 80 in the soft contact lens composition is 1.00 to 1.28. Method. Item 2-2. Item 2. The method according to Item 2-1, wherein the soft contact lens is a silicone hydrogel contact lens.

Moreover, this invention provides the manufacturing method of the composition for soft contact lenses of the aspect hung up below. Item 3-1. A method for producing a composition for soft contact lenses, comprising adding polysorbate 80 and at least one cooling agent selected from the group consisting of menthol, camphor, borneol and geraniol to a carrier containing water. And the manufacturing method of the composition for soft contact lenses whose polydispersion degree of the said polysorbate 80 in the said composition for soft contact lenses is 1.00-1.28. Item 3-2. Item 3. The manufacturing method according to Item 3-1, wherein the soft contact lens is a silicone hydrogel contact lens.

Moreover, this invention provides the method of suppressing the blurring of the eyes during soft contact lens wearing of the aspect hung up below. Claim | item 4-1. The polysorbate 80 comprising a step of contacting a soft contact lens with a composition for soft contact lens containing polysorbate 80 and at least one cooling agent selected from the group consisting of menthol, camphor, borneol and geraniol. A method for suppressing blurring of eyes during wearing of a soft contact lens caused by contact with the soft contact lens, wherein a polydispersity of the polysorbate 80 in the soft contact lens composition is 1.00 to 1. 28, the method. Item 4-2. Item 4. The method according to Item 4-1, wherein the soft contact lens is a silicone hydrogel contact lens.

Moreover, this invention provides the lens deformation inhibitor to the soft contact lens of the aspect hung up below. Item 5-1. A lens deformation inhibitor for soft contact lenses, comprising polysorbate 80 and at least one refreshing agent selected from the group consisting of menthol, camphor, borneol, and geraniol, wherein the lens deformation inhibitor in the lens deformation inhibitor A lens deformation inhibitor having a polydispersity of polysorbate 80 of 1.00 to 1.28. Item 5-2. Item 5. The lens deformation inhibitor according to Item 5-1, wherein the soft contact lens is a silicone hydrogel contact lens.

Moreover, this invention provides the blurring inhibitor of eyes during the soft contact lens wearing of the aspect hung up below. Item 6-1. A haze suppression agent for eyes during soft contact lens wearing, comprising polysorbate 80 and at least one refreshing agent selected from the group consisting of menthol, camphor, borneol and geraniol. A blurring inhibitor for eyes which has a polydispersity of the polysorbate 80 in the agent of 1.00 to 1.28. Item 6-2. The blurring inhibitor for eyes according to Item 6-1, wherein the soft contact lens is a silicone hydrogel contact lens.

According to one aspect of the present invention, it is possible to provide a composition for a soft contact lens capable of suppressing the deformation of the soft contact lens caused by the polysorbate 80. According to another aspect of the present invention, it is possible to provide a soft contact lens composition capable of suppressing blurring of eyes while wearing the soft contact lens.

It is a graph which shows the correlation with the polydispersion degree of the polysorbate 80, and the size change suppression rate of the lens by mix | blending a cooling agent.

Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments. In the present specification, the unit “w / v%” of the content ratio of the contained component means g / 100 mL.

1. Soft contact lens composition The soft contact lens composition according to the present embodiment (hereinafter sometimes simply referred to as “composition”) is selected from the group consisting of polysorbate 80 and menthol, camphor, borneol and geraniol. And at least one refreshing agent. The polydispersity of the polysorbate 80 in the soft contact lens composition is 1.00 to 1.28. Here, “1.00 to 1.28” means 1.00 or more and 1.28 or less.

The polysorbate 80 according to the present embodiment is not particularly limited as long as the polydispersity is 1.00 to 1.28. The polysorbate 80 having a polydispersity of 1.00 to 1.28 is obtained by measuring the polysorbate 80 obtained as a commercial product by the polydispersity measuring method described later, and the polydispersity is 1.00 to 1.28. It can be obtained by selecting polysorbate 80.

Alternatively, polysorbate 80 having a polydispersity of 1.00 to 1.28 can be obtained by further fractionating or purifying polysorbate 80 obtained as a commercial product by a known method. The method for fractionation or purification of the polysorbate 80 is not particularly limited, but purification using an ion exchange resin, activated carbon or adsorbent, steam deodorization, decolorization, dehydration and desolvation, filter filtration, cake filtration, centrifugation, sedimentation A method such as removal or a combination of two or more of these can be used. These fractionation or purification methods can be carried out if it is necessary to eliminate adverse effects on polydispersity measurement errors and the like. Other fractionation methods of the polysorbate 80 include, for example, a membrane filtration method, a distillation method, an extraction method or washing with an organic solvent, a reprecipitation method, a liquid / liquid separation method, or two or more of these methods. A combined method is mentioned. Specific examples include the following membrane filtration methods. The molecular weight and polydispersity of polysorbate 80 obtained as a commercial product are measured by the size exclusion chromatography (SEC) method described later, and an appropriate ultrafiltration membrane with a rejection rate close to 90% and a permeation flux is selected. . A commercially available filtration membrane can be used (for example, UF disk PLBC Ultracell RC 3K NMWL (molecular weight cut-off 3 KDa, cellulose membrane) (manufactured by Millipore Corporation)). A pressure of 0.5 to 200 Pa is applied according to the limit pressure of the filtration membrane. Since the number average molecular weight constituting the polydispersity does not change, polysorbate 80 having a polydispersity of 1.00 to 1.28 can be obtained by fractionation based on the weight average molecular weight. As other purification methods of the polysorbate 80, for example, crystallization, resin chromatography, a method of directly drying the reaction liquid with a spray dryer and pulverizing, a method of removing by steam distillation, an organic solvent and water were used. Examples include liquid-liquid extraction methods. Specific examples of the purification method include the following methods. First, polysorbate 80 is dissolved in methanol, the molecular weight at the critical micelle concentration is measured by a light scattering method, and the fractional molecular weight of the ultrafiltration membrane is determined. Next, membrane filtration is performed under conditions of a flow rate of 0.5 to 10 ml / min and a pressure of 0.1 to 20 bar.

Or although the manufacturing method in particular of the said polysorbate 80 is not restrict | limited, The polysorbate 80 whose polydispersity is 1.00-1.28 can be obtained with the following method. It is produced by adding ethylene oxide to a mixture obtained by partially esterifying sorbitol and / or sorbitol anhydride with a fatty acid mainly composed of oleic acid. The ester reaction can be carried out using sorbitan and a fatty acid under a basic catalyst, under an inert gas stream, at normal pressure or under reduced pressure, usually at a temperature of 150 to 280 ° C. After the reaction, neutralization is performed by adding a small amount of acid sufficient to deactivate the basic catalyst. The raw material sorbitol can be obtained by high-pressure hydrogen reduction of glucose, and a commercially available product may be used (for example, sorbitol D-70 (manufactured by Towa Kasei Kogyo Co., Ltd.), sorbitol S (Japan) Kenken Chemical Co., Ltd.)). Sorbitan can be obtained by dehydrating cyclization of sorbitol, and commercially available products may be used (for example, those manufactured by Toei Chemical Co., Ltd.). Alternatively, commercially available sorbitan oleate can also be used. The step of adding ethylene oxide to sorbitan fatty acid ester uses a catalyst such as an alkali metal catalyst and fatty acid soap. The manufactured polysorbate 80 can be filtered. The basic catalyst in the ester reaction includes alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and lithium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal hydrogen carbonates, alkali metals, Alkaline compounds such as alkaline earth metals, alkaline earth metal oxides, alkaline earth metal hydroxides, other metals, oxides thereof, and mixtures thereof, and phosphorous acid (salts) and / or hypoxia Combination with phosphoric acid (salt). Moreover, nitrogen or argon can be used for the inert gas used, for example. Examples of the metal catalyst for adding ethylene oxide to the product after the ester reaction include potassium hydroxide, sodium hydroxide, sodium methylate and the like. Polysorbate 80 having a polydispersity of 1.00 to 1.28 can be obtained by further fractionating or purifying the polysorbate 80 thus obtained by a known method.

Furthermore, the polysorbate 80 whose polydispersity is 1.00-1.28 can also be prepared by mixing the 2 or more types of polysorbate 80 from which polydispersion differs.

The composition for soft contact lenses according to the present embodiment is a polysorbate 80 having a polydispersity of 1.00 to 1.28 obtained as a commercially available product, and a polydispersity obtained by purifying a commercially available product by the above purification method. 1.00 to 1.28 polysorbate 80, or polysorbate 80 having a polydispersity of 1.00 to 1.28 produced by the above production method, and selected from the group consisting of menthol, camphor, borneol and geraniol. You may manufacture by the method including the process of mix | blending with an at least 1 sort (s) of refreshing agent. Moreover, you may manufacture by the method including the process of mix | blending the 2 or more types of polysorbate 80 obtained by the different method, and the at least 1 sort (s) of cooling agent selected from the group which consists of menthol, camphor, borneol, and geraniol. . By producing by such a method, the polydispersity of polysorbate 80 in the soft contact lens composition can be 1.00 to 1.28.

The polydispersity of polysorbate 80 is preferably 1.00 to 1.28, more preferably 1.00 to 1.26, still more preferably 1.00 to 1.24. It is still more preferable that it is 0.001 to 1.22, and it is especially preferable that it is 1.00 to 1.20. The polydispersity may be 1.10 to 1.26. By setting the polydispersity in such a range, the effects of the present invention such as the effect of suppressing deformation of the soft contact lens and the effect of improving blurring can be more remarkably exhibited.

The weight average molecular weight of polysorbate 80 is not particularly limited, but is preferably in the range of about 1200 to about 3200, more preferably about 1300 to about 3000. The number average molecular weight of polysorbate 80 is preferably in the range of about 700 to about 3000, more preferably about 800 to about 2000. By setting the weight average molecular weight and the number average molecular weight of the polysorbate 80 in the above ranges, the effects of the present invention such as the effect of suppressing deformation of the soft contact lens and the effect of improving blurring can be more remarkably exhibited. In addition, the measuring method and calculation method of a weight average molecular weight, a number average molecular weight, and polydispersity are as follows.

The content of the polysorbate 80 in the composition is appropriately set according to the use of the composition, the preparation form, etc., but is generally 0.0001 to 8 w as the total amount of the polysorbate 80 with respect to the total amount of the composition. / V%, preferably 0.001 w / v% to 4 w / v%, and more preferably 0.002 w / v% to 2 w / v%. By setting the content of the polysorbate 80 in the above range, the effects of the present invention such as the effect of suppressing deformation of the soft contact lens and the effect of improving blurring can be more remarkably exhibited.

The refreshing agent according to the present embodiment is at least one selected from the group consisting of menthol, camphor, borneol and geraniol, and these may be any of d-form, l-form and dl-form. Preferred are l-menthol, d-camphor, dl-camphor and d-borneol. Moreover, you may contain as a part of essential oil component. The said cooling agent may be used individually by 1 type, and may be used in combination of 2 or more type.

The content of the refreshing agent in the composition is appropriately set according to the use of the composition, the formulation form, etc., but is usually 0.0001 w / v% to 0.00% relative to the total amount of the composition. It is preferably 5 w / v%, more preferably 0.001 w / v% to 0.1 w / v%. By making content of a refreshing agent into the above ranges, effects of the present invention such as an effect of suppressing deformation of a soft contact lens and an effect of improving blurring can be more remarkably exhibited.

The content ratio of the refreshing agent and polysorbate 80 is not particularly limited, but it is preferable to contain 0.5 to 100 parts by weight of polysorbate 80 with respect to 1 part by weight of the refreshing agent, and with respect to 1 part by weight of the refreshing agent. More preferably, the polysorbate 80 is contained in an amount of 1 to 100 parts by weight, and more preferably 2 to 50 parts by weight of the polysorbate 80 with respect to 1 part by weight of the cooling agent. The ratio between the content of the refreshing agent and the polydispersity value of the polysorbate 80 is not particularly limited, but the polydispersity of the polysorbate 80 is preferably 15 to 2000 with respect to 1 part by weight of the refreshing agent. The polydispersity of the polysorbate 80 is more preferably 20 to 1900 with respect to parts by weight. By making the content ratio of the polysorbate 80 with respect to the refreshing agent and the ratio of the polydispersity value of the polysorbate 80 with respect to the content of the refreshing agent within the above ranges, adsorption of the refreshing agent to the SCL and irritation to the eyes The effects of the present invention such as the effect of suppressing the adverse effects such as the above, the effect of suppressing the deformation of the soft contact lens, and the effect of improving the blurring can be more remarkably exhibited.

The composition is applicable to any soft contact lens as long as it is a known soft contact lens. The “soft contact lens” (SCL) shown in the present specification is a soft contact lens with respect to a hard contact lens having a hard feel. As a method for classifying soft contact lenses, there are soft contact lens classification methods described in ISO18369-1: 2006 and ISO18369-1: AMENDENT1. For example, SCLs belonging to Group I have a common property that the moisture content is less than 50%, and the mole percentage of monomers having anions out of the constituent monomers of the raw material polymer is less than 1%.

Also known is a silicone hydrogel contact lens obtained by copolymerizing a hydrophilic monomer (eg, hydroxyethyl methacrylate, dimethylacrylamide, etc.) with a silicone-containing material (eg, TRIS or TRIS derivative, which is a polymer of silicone and acrylate). ing. Examples of material names based on USAN (United State Adopted Name) of silicone hydrogel contact lenses include Lotrafilcon A, Lotrafilcon B, Balafilcon A, Galificon A, Senofilcon A, Narafilcon, and Arafilon.

The soft contact lens composition according to this embodiment is suitable for a silicone hydrogel contact lens (SHCL). Especially, it is suitable for SHCL having a moisture content of less than 75%, more suitable for SHCL having oxygen permeability of 40 Dk or more from another viewpoint, and particularly suitable for SHCL having oxygen permeability of 50 Dk or more. It is. Among them, it is suitable for SHCL containing Galyconcon A as a material.

The polydispersity of polysorbate 80 is defined as _Mw / _Mn . M _w represents a weight average molecular weight, and M _n represents a number average molecular weight.

Various molecular weight measurement methods such as liquid chromatography, ultracentrifugation, light scattering, and intrinsic viscosity are known. Depending on the measurement method, the type of average molecular weight obtained, such as the weight average molecular weight and the number average molecular weight, and the measurable molecular weight range are different. The polydispersity defined by the present invention is measured by a size exclusion chromatography (SEC) method. The SEC method can measure the weight average molecular weight, the number average molecular weight, and the polydispersity, and is easy to operate. Therefore, the SEC method is most widely used for the measurement of polymer compounds and oligomers. The SEC method uses a column packed with a gel with pores, and has a mechanism for separation by different elution times due to differences in the moving distance in the column depending on the molecular size in the sample solution. Average molecular weights such as M _w and M _n are calculated based on a calibration curve prepared with a standard substance having a known molecular weight. Thus, since the polydispersity obtained by the SEC method is a relative value obtained by performing molecular weight calibration using a standard substance, it is a value obtained only by carrying out under the same conditions. Therefore, the SEC method of the present invention is defined as using polyethylene oxide and polyethylene glycol as standard substances as described later. Moreover, since it is a relative value, it is also important to set conditions in the separation of test components and the creation of a calibration curve. In view of the characteristics of these SEC methods, the present inventors diligently studied the measurement conditions of the SEC method in order to increase the accuracy of polydispersity calculation of the polysorbate 80.

In the present embodiment, the weight average molecular weight, number average molecular weight, and polydispersity of polysorbate 80 in the soft contact lens composition are measured as follows. (Preparation of calibration curve solution) Polyethylene oxide (Tosoh Corporation) and polyethylene glycol (Wako Pure Chemical Industries, Ltd.) having a molecular weight of several hundred thousand to several hundreds are used as standard substances. Polyethylene oxide and polyethylene glycol as standard substances have three types with molecular weights of several hundred thousand, two types with molecular weights of tens of thousands, two types with molecular weights of thousands, and molecular weights of hundreds. It is preferable to use one type. More preferably, polyethylene oxide having a molecular weight of 580000, 255000, 146000, 44900, 27000 and polyethylene glycol having a molecular weight of 8000, 1000, 600 are used and divided into molecular weights of 580000, 146000, 27000, 1000 and molecular weights of 255000, 44900, 8000, 600. Combine so that the elution positions do not overlap. 2. An aqueous solution with a standard substance concentration of 0.1 w / v% is prepared and used as a standard solution. Setting the concentration of the standard substance to 0.1 w / v% is very important in order to suppress the relative standard deviation of polydispersity. 3. A standard solution of 1.0 mL is accurately taken, and a solution obtained by accurately adding 4.0 mL of methanol is used as a calibration curve solution. (Preparation of sample solution) 4. Take 1.0 mL of the test solution accurately, and accurately add 4.0 mL of methanol as the sample solution. (Measurement by liquid chromatograph) 5. Each calibration curve solution and sample solution are measured with a liquid chromatograph (Agilent 1200 series, manufactured by Agilent Technologies). 6). The columns are manufactured by Tosoh Corporation. TSK-Gelα-4000 (exclusion limit molecular weight of about 400,000) and TSK-Gelα-2500 (exclusion limit molecular weight of about 5000) filled with a hydrophilic vinyl polymer (both columns have an inner diameter of 7.8 mm, 300 mm long) are connected and installed one by one in this order. The column temperature is 40.0 ° C. Keeping 40.0 ° C. constant is very important to suppress the relative standard deviation of polydispersity. 7. As the eluent, a mixed solution in which the volume of methanol is 4.0 times the 0.10 mol / L sodium chloride test solution is prepared and used for each measurement. Including sodium chloride in the eluent to suppress the interaction between sample molecules or between the sample molecules and the filler is very important in order to suppress the relative standard deviation of polydispersity. 8). The flow rate is 0.5 mL / min. 9. The injection volume is 50 μL. Filter through a 0.45 μm filter prior to injection. 10. The calibration curve solution and the sample solution were measured in this order, and the analysis cycle was 60 minutes for the calibration curve solution and 90 minutes for the sample solution. It is very important to continuously measure the calibration curve solution and the sample solution without interrupting the measurement in order to suppress the relative standard deviation of polydispersity. 11. The detector is a differential refractive index detector, and the detector temperature is 35.0 ° C. (Calculation of polydispersity) 12. The obtained chromatogram is analyzed by an SEC analyzer, and the weight average molecular weight and number average molecular weight are calculated for the range sandwiched between the chromatogram curve and the baseline. The elution time and molecular weight value of each peak are plotted from the calibration curve solution, approximated by a linear equation to obtain a calibration curve, and the correlation coefficient is 0.99 or more. Furthermore, in order to reduce errors in chromatogram analysis processing, the obtained peaks are vertically divided at intervals of 0.1 minutes or more and less than 0.001 minutes to calculate the average molecular weight. 13. The polydispersity is calculated from the formula of _Mw / _Mn . 4. above. The sample solution of the process shown by is measured 3 times, and the average value of the polydispersities obtained in each is adopted as the polydispersity of the present application.

The relative standard deviation of the average molecular weight in the generally known SEC method is calculated by the following formulas A and B and is about 4 to 5%. Since the relative standard deviation of polydispersity is less than 5% under the above SEC measurement conditions, it can be said that the measurement conditions are appropriate. The polydispersity in the present application is measured and calculated so that the relative standard deviation is less than 5%. When the above-mentioned reagents, columns, liquid chromatographs and the like are not available, measurements can be performed using alternatives equivalent to these. However, it is necessary to measure so that the relative standard deviation of polydispersity is less than 5%. When the relative standard deviation is 5% or more, it is necessary to suppress the relative standard deviation within the examination range of the measurement conditions normally performed. In order to suppress the relative standard deviation in the study by the present inventors, it is important that the above conditions are satisfied with respect to the concentration of the standard substance, the column temperature, the composition of the eluent, and the analysis cycle of the calibration curve solution and the sample solution. It was.

The composition for soft contact lenses according to the present embodiment may contain an appropriate amount of various pharmacologically active ingredients and physiologically active ingredients in addition to the above-mentioned ingredients as long as the effects of the present invention are not hindered. Such an ingredient is not particularly limited, and examples thereof include an active ingredient in an ophthalmic drug described in the over-the-counter drug manufacturing (import) approval standard 2000 edition (supervised by the Pharmaceutical Affairs Research Committee). Specifically, the following components are listed as components used in ophthalmic drugs. Antihistamines: diphenhydramine hydrochloride, chlorpheniramine maleate and the like. Decongestant: Tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline nitrate, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride, and the like. Vitamins: flavin adenine dinucleotide sodium, cyanocobalamin, retinol acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, calcium pantothenate, sodium pantothenate, tocopherol acetate, etc. Amino acids: potassium aspartate, magnesium aspartate, aminoethylsulfonic acid and the like. Anti-inflammatory agent: dipotassium glycyrrhizinate, allantoin, ε-aminocaproic acid, berberine chloride, berberine sulfate, lysozyme chloride, sodium azulene sulfonate, and the like. Astringent: zinc white, zinc lactate, zinc sulfate, etc. Others: sodium hyaluronate, sodium chondroitin sulfate, sulfamethoxazole, sodium sulfamethoxazole, sulfisoxazole, sodium sulfisomidine, neostigmine methyl sulfate, alginic acid and the like.

In the composition for soft contact lenses according to the present embodiment, various additives may be appropriately selected according to a conventional method depending on the use and form as long as the effects of the invention are not impaired. The above may be used in combination to contain an appropriate amount. Examples of these additives include various additives described in Pharmaceutical Additives Encyclopedia 2007 (edited by Japan Pharmaceutical Additives Association). Typical additives include the following additives. Carrier: Aqueous carrier such as water or hydrous ethanol. Thickener: hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, sodium chondroitin sulfate, hydroxyethylcellulose, methylcellulose, sodium carboxymethylcellulose and the like. Sugars: glucose, cyclodextrin, etc. Sugar alcohols: xylitol, sorbitol, mannitol, glycerin, etc. These may be d-form, l-form or dl-form. Preservatives, bactericides or antibacterial agents: alkylpolyaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, paraoxybenzoate Acid ethyl, propyl paraoxybenzoate, butyl paraoxybenzoate, phenethyl alcohol, benzyl alcohol, polyhexamethylene biguanide, chlorhexidine gluconate and the like. Buffer: boric acid, aminoethylsulfonic acid, epsilon-aminocaproic acid, sodium citrate, polyethylene glycol, propylene glycol, sodium bisulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, disodium hydrogen phosphate , Sodium dihydrogen phosphate, potassium dihydrogen phosphate and the like. pH adjuster: hydrochloric acid, boric acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium bicarbonate, sodium carbonate, borax, triethanolamine, monoethanolamine, diisopropanol Amines and the like. Stabilizer: Dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate, etc. Chelating agents: ascorbic acid, edetate tetrasodium, edetate sodium, citric acid, etc. Fragrance or other refreshing agent: anethole, eugenol, cineol, limonene, ryuuno, etc. These may be either d-form, l-form or dl-form, and are formulated as essential oils (mint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, bergamot oil, eucalyptus oil, rose oil, etc.) May be.

The composition for soft contact lenses according to the present embodiment can take various preparation forms depending on the purpose. For example, a liquid agent, a gel agent, etc. are mentioned as a form of the said composition for soft contact lenses. A liquid is preferable, and an aqueous liquid is more preferable. Here, the aqueous liquid means a liquid containing water, and usually contains 75% by weight or more, preferably 80% by weight or more, more preferably 85% by weight or more, still more preferably 90% by weight of water in the composition. % Or more is meant. The water contained in the aqueous liquid may be any pharmaceutical, pharmacological (pharmaceutical) or physiologically acceptable. For example, distilled water, normal water, purified water, sterilized purified water, water for injection, distilled water for injection, and the like can be used. These definitions are based on the 16th revised Japanese Pharmacopoeia.

The pH of the soft contact lens composition according to this embodiment is not particularly limited as long as it is within a range that is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. As pH of the composition for soft contact lenses, it is preferable that it is 4.0-9.5, for example, it is more preferable that it is 5.0-9.0, and it is 5.5-8.5. Is more preferable.

The osmotic pressure of the composition for soft contact lenses according to the present embodiment is not particularly limited as long as it is within a range acceptable for a living body. The osmotic pressure ratio of the soft contact lens composition is, for example, preferably 0.5 to 5.0, more preferably 0.6 to 3.0, and 0.7 to 2.0. More preferably.

About the viscosity of the composition for soft contact lenses which concerns on this embodiment, if it is a range accept | permitted by a biological body, it will not specifically limit. The viscosity at 20 ° C. measured with a rotational viscometer (RE550 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1 ° 34 ′ × 24) is preferably 0.01 to 10,000 mPa · s, for example, 0.05 More preferably, it is -8000 mPa * s, and it is still more preferable that it is 0.1-6000 mPa * s.

The soft contact lens composition according to the present embodiment is prepared by adding the polysorbate 80, the refreshing agent, and other components as necessary to the carrier so as to have a desired concentration. For example, the polysorbate 80 and the refreshing agent can be combined and stirred, and then purified water can be added to emulsify or dissolve, adjusted to a predetermined pH and osmotic pressure, and sterilized by filtration sterilization or the like.

Examples of the soft contact lens composition according to the present embodiment include a metal, glass, or plastic container. The plastic container is made of polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polypropylene (PP), polyarylate (PAR), polybutylene terephthalate (PBT), and polycarbonate (PC). In any container selected from the group consisting of: Preferably, they are made of PET, PEN, PP, PAR, PC or glass, and more preferably made of PET, PP or glass. When a container is a synthetic resin, the container may be shape | molded only from the single synthetic resin, and may be shape | molded combining several synthetic resin.

If the composition for soft contact lenses which concerns on this embodiment is used in the ophthalmic field | area and is used so that it may contact a soft contact lens, the form and application will not be restrict | limited. For example, eye drops for soft contact lenses (eye drops that can be used while wearing soft contact lenses), eye drops for soft contact lenses (eye wash that can be used while wearing soft contact lenses), soft contact lens mounting solutions, Examples thereof include soft contact lens care solutions (soft contact lens disinfecting solution, soft contact lens preserving solution, soft contact lens cleaning solution, soft contact lens cleaning preserving solution, and the like).

The soft contact lens composition can suppress the deformation of the soft contact lens by contacting with the soft contact lens.

2. Method for suppressing deformation of soft contact lens A method for suppressing deformation of a soft contact lens according to the present embodiment comprises polysorbate 80 and at least one cooling agent selected from the group consisting of menthol, camphor, borneol and geraniol. A method for suppressing deformation of a soft contact lens, comprising a step of bringing the soft contact lens composition into contact with the soft contact lens, wherein the polydispersity of the polysorbate 80 in the soft contact lens composition is 1.00 to 1.28. Components used in the method for suppressing deformation of the soft contact lens, content, measurement method of polydispersity, other conditions, etc. are as follows. It is the same as the composition for soft contact lenses.

3. Method for Producing Composition for Soft Contact Lens A method for producing a composition for soft contact lens according to the present embodiment comprises polysorbate 80 having a polydispersity of 1.00 to 1.28, menthol, camphor, borneol and geraniol. A step of blending with at least one refreshing agent selected from the group consisting of: The components used in the method for producing the composition for soft contact lenses, the content, the measuring method such as polydispersity, and other conditions are as follows. It is the same as the composition for soft contact lenses.

4). Method for suppressing blurring of eyes while wearing soft contact lenses The method for suppressing blurring of eyes while wearing soft contact lenses according to this embodiment is selected from the group consisting of polysorbate 80 and menthol, camphor, borneol and geraniol. A method of contacting a soft contact lens with a soft contact lens composition containing at least one refreshing agent, wherein the polydispersity of the polysorbate 80 in the soft contact lens composition is 1.00 to 1.28. Components, content, measuring methods such as polydispersity, and other conditions in the soft contact lens composition used in the above method are as follows. It is the same as the composition for soft contact lenses.

5). Lens Deformation Inhibitor of Soft Contact Lens The lens deformation inhibitor according to this embodiment contains polysorbate 80 and at least one cooling agent selected from the group consisting of menthol, camphor, borneol, and geraniol. The polydispersity of the polysorbate 80 in the lens deformation inhibitor is 1.00 to 1.28. Measurement methods such as components, content, polydispersity, and other conditions in the lens deformation inhibitor are as follows. It is the same as the composition for soft contact lenses.

6). Blurring inhibitor of eye during wearing soft contact lens The haze inhibiting agent of eye during wearing soft contact lens according to the present embodiment is at least one selected from the group consisting of polysorbate 80, menthol, camphor, borneol and geraniol. And a refreshing agent. The polydispersity of the polysorbate 80 in the haze control agent is 1.00 to 1.28. Measurement methods such as components, content, polydispersity, and other conditions in the above-mentioned haze inhibitor are as follows. It is the same as the composition for soft contact lenses.

According to the present invention, it is possible to provide a composition for soft contact lens that suppresses corneal epithelial disorder by reducing the deterioration of contact lens-eye fitting by suppressing deformation of the soft contact lens caused by polysorbate 80. become. Furthermore, according to the present invention, it is possible to provide a composition for soft contact lenses that can maintain visual acuity correction power by suppressing blurring of eyes while wearing soft contact lenses.

Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.

Test Example 1-1. Test for Size Change of Soft Contact Lens (1) Preparation of Soft Contact Lens Composition Soft contact lens compositions according to Examples 1 to 4 and Comparative Examples 1 to 3 were prepared by the following method.

Using polysorbates 80 having different polydispersities described in Table 1, test solutions described in Table 2 were prepared. Those containing a in the test solution name indicate a test solution containing a cooling agent such as l-menthol, and those containing b in the test solution name indicate a test solution not containing a cooling agent such as l-menthol. The lens size change was calculated by a method described later for each, and the size change suppression rate was calculated using these values. For example, the suppression rate of the size change of the comparative example 1 was calculated using the lens size change of the comparative example 1a and the comparative example 1b. Polysorbate 80 in all test solutions was measured by the SEC measurement method described above, and the polydispersity was calculated and shown in Table 2. In Table 2, the amount of each component is shown in w / v%.

(2) Evaluation of size change of soft contact lens Soft contact lens (USAN name: Garyfilcon A; water content 47.0%, nonionic, POWER-3.00, BC8.7 in 10 mL of physiological saline solution) , DIA 14.0 mm) each was immersed and allowed to stand at 34 ° C. for 4 hours or more. A physiological projector and a soft contact lens are transferred to a cell from a glass vial controlled at a constant temperature of 34 ° C. using a water bath and the cell is filled with the physiological saline (product name: PROFILE PROTECTOR V -128, manufactured by Nikon), and the size (diameter) of the soft contact lens was measured (start value). In order not to change the temperature of the soft contact lens, the time from taking out from the water bath to measuring is shortened within about 20 seconds, and the time from taking out to measuring becomes the same between samples. It was measured. Subsequently, the soft contact lens which measured the start value was immersed in 10 mL of each test solution produced according to Table 2, and left still at 34 degreeC for 24 hours. After 24 hours, the inside of the cell was washed with a separately prepared 34 ° C. test solution, the test solution in the vial and the soft contact lens were transferred to the cell, and the lens size was measured by the same method as above ( Processed value). The size change amount of the soft contact lens was calculated by subtracting the start value from the processed value (Equation 1). Furthermore, using the following (Formula 2), the inhibition rate of the size change of the soft contact lens of the test solution containing l-menthol (cooling agent) relative to the test solution not containing l-menthol (cooling agent) was calculated. . Lens size change (mm) = post-treatment value-start value (Equation 1) size change inhibition rate (%) = (lens size change of test solution not containing cooling agent (mm) -test containing cooling agent Change in lens size of liquid (mm)) / (Change in lens size of test liquid not containing cooling agent) × 100 (Formula 2)

FIG. 1 shows a correlation diagram between the polydispersity of polysorbate 80 in the test solution and the suppression rate of lens size change (diamonds in FIG. 1). In Comparative Examples 1 to 3 in which the polydispersity of polysorbate 80 in the test solution is 1.29 or more, the inhibition rate is negative, whereas the polydispersity is 1.26 or less. In Examples 1-4, it turned out that the suppression rate has shown the positive value.

Whether or not M _n also has a correlation with the suppression rate of lens size change was examined, but no significant correlation could be found.

Test Example 1-2. Test for Size Change of Soft Contact Lens (1) Preparation of Composition for Soft Contact Lens Using polysorbate 80 having different polydispersities shown in Table 1, test solutions shown in Table 3 were prepared. In Table 3, the amount of each component is shown in w / v%.

(2) Evaluation of size change of soft contact lens The change in lens size was evaluated in the same manner as in Test Example 1-1, and the suppression rate of the size change of the soft contact lens by the cooling agent was calculated. FIG. 1 shows a correlation diagram between the polydispersity of polysorbate 80 in the test solution and the suppression rate of lens size change due to d-camphor (square marks in FIG. 1). In Comparative Example 4 in which the polydispersity of polysorbate 80 in the test solution is 1.29, the inhibition rate shows a negative value, whereas the polydispersity is 1.26 or less. 6, it was found that the inhibition rate showed a positive value. That is, even when the cooling agent to be combined was d-camphor, the same behavior as menthol was exhibited.

Test Example 1-3. Test for Size Change of Soft Contact Lens (1) Preparation of Composition for Soft Contact Lens Using polysorbate 80 having different polydispersities shown in Table 1, test solutions shown in Table 4 were prepared. In Table 4, the amount of each component is shown in w / v%.

(2) Evaluation of size change of soft contact lens The change in lens size was evaluated in the same manner as in Test Example 1-1, and the suppression rate of the size change of the soft contact lens by the cooling agent was calculated. FIG. 1 shows a correlation diagram between the polydispersity of polysorbate 80 in the test solution and the suppression rate of lens size change due to d-borneol (triangle mark in FIG. 1). In Comparative Example 5 where the polydispersity of polysorbate 80 in the test solution is 1.29, the inhibition rate shows a negative value, whereas the above polydispersities are 1.26 or less. 8, it was found that the inhibition rate showed a positive value. That is, even when the cooling agent to be combined was d-borneol, the same behavior as menthol and d-camphor was exhibited.

Test Example 2 Evaluation of blurring of eyes while wearing a soft contact lens Soft contact lens (any one of groups I, IV, and V in the soft contact lens classification method described in ISO18369-1: 2006 and ISO18369-1: AMENDMENT1) 5 people were instilling 1 to 2 drops of the prescription solution shown in Table 5 once a day and using a 10 cm straight line with a scale from 0 to 100 shown in Table 6, using the VAS method. The haze of the eyes was evaluated with (Visual Analog Scale). In Table 5, the amount of each component is shown in w / v%. For the instillation 5 times a day, the next instillation was performed after a sufficient time after one instillation. Table 5 shows the average score of the haze evaluation of five people.

Table 5 shows the haze evaluation results of the eyes. In Comparative Examples 6 and 7 in which the polydispersity of polysorbate 80 in the test solution is 1.29 or more, blurred eyes appear to be uncomfortable, whereas the polydispersity is 1.26 or less. 9 and 10 showed no haze.

Claims (1)

A composition for soft contact lenses comprising polysorbate 80 and at least one refreshing agent selected from the group consisting of menthol, camphor, borneol and geraniol, wherein the composition in the composition for soft contact lenses The composition for soft contact lenses whose polydispersion degree of polysorbate 80 is 1.00-1.28.

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