JP6537223B2 - Composition for soft contact lens - Google Patents

Description

  The present invention relates to a composition containing a refreshing agent and polysorbate 80 and applied to a soft contact lens. The present invention also relates to a method of suppressing the deformation of a soft contact lens caused by polysorbate 80. The present invention also relates to a method of suppressing eye haze during wearing of a soft contact lens with a composition containing a refreshing agent and Polysorbate 80.

  The development of contact lenses starts with glass lenses and has been developed in various ways, such as hard plastic lenses and hydrous plastic lenses. The contact lens is required to be excellent in optical characteristics and biocompatibility in any use purpose such as correction of visual acuity, treatment of eye diseases, examination, fashion and the like. In the case of biocompatibility of contact lenses, problems of safety and poor feeling of wearing are problems. For example, when the amount of oxygen supplied to cells in the eye decreases, proliferation of corneal epithelial cells and thickening of the cornea occur. Therefore, although it is thought that a problem may occur in safety, for example, eye problems may occur due to deterioration in fitting with a contact lens, etc., but the cause has not been elucidated. Besides, although many problems are pointed out when wearing a contact lens, it is considered that the causal relationship is complicated and the mechanism is not clarified.

  Therefore, development of materials for contact lenses has been focused on various causal relationships, and contact lenses having various properties have been put on the market. Hard contact lenses made of hard materials and soft contact lenses (SCL) made of soft materials have become widespread. For example, silicone hydrogel contact lenses (SHCL) in which silicone is blended with hydrogel have been widely spread in recent years.

  In parallel with the launch of soft contact lenses having various properties, various compositions applied to soft contact lenses have also been developed to enhance safety and comfort. For example, an eye drop for a soft contact lens (Patent Document 1) containing a refreshing agent and a surfactant, wherein the compounding amount of the surfactant is 10 to 100 times that of the refreshing agent. Are known. In addition, an eye drop applicable for wearing a contact lens, which contains a nonionic surfactant selected from tranilast or a pharmacologically acceptable salt thereof, polyvinyl pyrrolidone, and polyoxyethylene hydrogenated castor oil (patent Reference 2) is known. Furthermore, an ophthalmic composition for a soft contact lens comprising 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 the feeling of wearing of the contact lens wearer are not sufficient, and further improvement is required.

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

The present inventors have been variously examining a composition containing polysorbate 80 (polyoxyethylene (20) sorbitan monooleate). The action mechanism according to the deformation of the soft contact lens is the same as that of polysorbate 80. I got a completely new finding that it differs depending on the specific nature. Heretofore, it has been known that nonionic surfactants change the size of a soft contact lens (Patent Document 2, Patent Document 3). However, it has not been known until now 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.
In addition, it is feared that the change in the shape of the contact lens adversely affects the vision correction power of the contact lens. Furthermore, it may cause various eye symptoms and deterioration of the feeling of wearing.

  One 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 the deformation of the soft contact lens caused by the polysorbate 80. Another aspect of the present invention is made in view of the above-mentioned circumstances, and an object of the present invention is to provide a composition for a soft contact lens capable of suppressing eye blur while wearing a 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), but the present inventors are keen to solve the above problems. As a result of examination, when the polydispersity of polysorbate 80 contained in the composition for soft contact lens is within a specific numerical range, the lens is made to further contain a specific refreshing agent such as menthol in the composition. It has been found that deformation is suppressed.
Polysorbates are generally selected and used with HLB (Hydrophile-Lipophile Balance) showing balance of hydrophilicity and lipophilicity as an index, in expectation of effects such as emulsification, dispersion, wetting and the like. The polydispersity calculated by the ratio of the weight average molecular weight to 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 focus on the correlation between the polydispersity of 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, the present invention provides a composition for a soft contact lens of the following aspect. Although the details of the mechanism of suppressing the deformation of the soft contact lens by making the polydispersity of polysorbate 80 into the following range have not been clarified, the difference of the polydispersity makes the micellar structure of polysorbate 80 and the refreshing agent The influence on the speed of interaction with the matrix of the soft contact lens, which is a slightly different, hydrated one kind of gel, is also considered as a factor.

Item 1-1. A composition for a soft contact lens comprising polysorbate 80 and at least one refreshing agent selected from the group consisting of menthol, camphor, borneol and geraniol, said polysorbate in said composition for soft contact lens The composition for soft contact lenses whose polydispersity of 80 is 1.00 to 1.28.
Item 1-2. The composition for soft contact lenses according to Item 1-1, wherein the polydispersity of the polysorbate 80 in the composition for soft contact lenses is 1.00 to 1.26.
Item 1-3. The method according to any one of Items 1-1 and 1-2, wherein the content of the polysorbate 80 in the composition for a soft contact lens is 0.5 to 100 parts by weight with respect to 1 part by weight of the refreshing agent. Composition for Soft Contact Lenses.
Item 1-4. The composition for soft contact lenses according to any one of items 1-1 to 1-3, wherein the content of the refreshing agent in the composition for soft contact lenses 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 composition for soft contact lens is 15 to 2000 with respect to 1 part by weight of the refreshing agent Composition.
Item 1-6. The composition for soft contact lenses according to any one of Items 1-1 to 1-5, which is for silicone hydrogel contact lenses.

The present invention also provides a method for suppressing the deformation of the soft contact lens according to the aspects listed below.
Item 2-1. Contacting the composition for a soft contact lens containing the composition with polysorbate 80 and at least one refreshing agent selected from the group consisting of menthol, camphor, borneol and geraniol with the soft contact lens 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 composition for soft contact lens is 1.00 to 1.28. Method.
Item 2-2. The method according to item 2-1, wherein the soft contact lens is a silicone hydrogel contact lens.

The present invention also provides a method for producing a composition for soft contact lens according to the aspect described below.
Item 3-1. A method for producing a composition for a soft contact lens, comprising adding polysorbate 80 and at least one refreshing agent selected from the group consisting of menthol, camphor, borneol and geraniol to a carrier containing water. The method for producing a composition for soft contact lens, wherein the polydispersity of the polysorbate 80 in the composition for soft contact lens is 1.00 to 1.28.
Item 3-2. The manufacturing method according to item 3-1, wherein the soft contact lens is a silicone hydrogel contact lens.

The present invention also provides a method for suppressing eye blur during soft contact lens wear according to the embodiments described below.
Item 4-1. Contacting the composition for a soft contact lens containing the composition with polysorbate 80 and at least one refreshing agent selected from the group consisting of menthol, camphor, borneol and geraniol with the soft contact lens It is a method to suppress eye blur during wearing of a soft contact lens caused by bringing the soft contact lens into contact, and the polydispersity of the polysorbate 80 in the composition for soft contact lens is 1.00 to 1. 28 is the way.
Item 4-2. The method according to item 4-1, wherein the soft contact lens is a silicone hydrogel contact lens.

The present invention also provides a lens deformation inhibitor for a soft contact lens according to the aspects listed below.
Item 5-1. A lens deformation inhibitor for a soft contact lens, comprising polysorbate 80 and at least one refreshing agent selected from the group consisting of menthol, camphor, borneol and geraniol, which is contained in the lens deformation inhibitor. The lens deformation inhibitor whose polydispersity of polysorbate 80 is 1.00 to 1.28.
Item 5-2. The lens deformation inhibitor according to item 5-1, wherein the soft contact lens is a silicone hydrogel contact lens.

The present invention also provides an eye haze inhibitor during soft contact lens wear according to the embodiments listed below.
Item 6-1. An eye haze suppressant during wearing of a soft contact lens, comprising polysorbate 80 and at least one refreshing agent selected from the group consisting of menthol, camphor, borneol and geraniol, which suppresses the eye haze Eye haze inhibitor, wherein the polysorbate 80 in the agent has a polydispersity of 1.00 to 1.28.
Item 6-2. The eye haze inhibitor 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 composition for a soft contact lens capable of suppressing eye haze while wearing a soft contact lens.

It is a graph which shows correlation with the polydispersity of polysorbate 80, and the size change suppression rate of the lens by mix | blending a refreshing 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 component means g / 100 mL.

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

  The polysorbate 80 according to this 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 a polydispersity measuring method described later, and has a polydispersity of 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 fractionation or purification method of the polysorbate 80 is not particularly limited, but purification treatment using ion exchange resin, activated carbon or adsorbent, steam deodorization treatment, decolorization treatment, dehydration removal solvent, filter filtration, cake filtration, centrifugation, sedimentation A method such as removal or a combination of two or more of them can be used. These fractionation or purification methods can be performed if it is necessary to remove the adverse effect on the measurement error of polydispersity and the like. Other fractionation methods of the above polysorbate 80 include, for example, membrane filtration method, distillation method, extraction method with organic solvent or washing, reprecipitation method, liquid / liquid separation method, or two or more of them. The combined method is mentioned. The following membrane filtration method is mentioned as a specific example. 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 of about 90% and a permeation flux is obtained is selected. . A commercially available filter membrane can be used (for example, UF disc 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, it is possible to obtain polysorbate 80 having a polydispersity of 1.00 to 1.28 by fractionation based on the weight average molecular weight.
As other purification methods of the above-mentioned polysorbate 80, for example, a method of crystallization and resin chromatography, a method of drying the reaction liquid as it is with a spray drier as it is and pulverizing, a method of removing by steam distillation, an organic solvent and water The liquid-liquid extraction method etc. are mentioned. As a specific example of the said purification method, the following method is mentioned, for example. First, polysorbate 80 is dissolved in methanol, and the molecular weight at the critical micelle concentration is measured by the light scattering method to determine the fractional molecular weight of the ultrafiltration membrane. Next, membrane filtration is performed under the conditions of a flow rate of 0.5 to 10 ml / min and a pressure of 0.1 to 20 bar.

  Alternatively, the method for producing the polysorbate 80 is not particularly limited, but polysorbate 80 having a polydispersity of 1.00 to 1.28 can be obtained by the following method. Ethylene oxide is added to a partially esterified mixture of sorbitol and / or anhydrous sorbitol with a fatty acid mainly consisting of oleic acid. The ester reaction can be carried out at a temperature of usually 150 to 280 ° C., sorbitan and fatty acid under basic catalyst, under a stream of inert gas, under normal pressure or reduced pressure. After the reaction, neutralization is carried out 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, or a commercially available product may be used (for example, Sorbit D-70 (manufactured by Towa Chemical Industry Co., Ltd.), Sorbitol S (day) (Manufactured by Ken Chemical Co., Ltd.) and the like. Sorbitan can be obtained by dehydrating cyclization of sorbitol, or a commercially available product may be used (eg, manufactured by Toei Chemical Co., Ltd., etc.). Alternatively, commercially available sorbitan oleate can also be used. The step of adding ethylene oxide to sorbitan fatty acid ester uses catalysts such as alkali metal catalysts and fatty acid soaps. The manufactured polysorbate 80 can be filtered. The basic catalyst in the ester reaction is an alkali metal hydroxide such as sodium hydroxide, potassium hydroxide and lithium hydroxide, an alkali metal carbonate such as sodium carbonate and potassium carbonate, an alkali metal hydrogencarbonate, an alkali metal, Alkaline compounds such as alkaline earth metals, alkaline earth metal oxides, alkaline earth metal hydroxides, other metals, their oxides, and mixtures thereof, phosphorous acid (salt) and / or hypophosphorous acid It is combined use with phosphoric acid (salt). Also, the inert gas used may be, for example, nitrogen or argon. 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. By further fractionating or purifying polysorbate 80 thus obtained by a known method, polysorbate 80 having a polydispersity of 1.00 to 1.28 can be obtained.

  Furthermore, polysorbate 80 having a polydispersity of 1.00 to 1.28 can also be prepared by mixing two or more polysorbates 80 having different polydispersities.

  The composition for soft contact lens according to the present embodiment is a polysorbate 80 having a polydispersity of 1.00 to 1.28 obtained as a commercial product, and a polydispersity obtained by purifying a commercial product by the above-mentioned purification method. It is selected from the group consisting of menthol, camphor, borneol and geraniol, polysorbate 80 having a viscosity of 1.00-1.28, or polysorbate 80 having a polydispersity of 1.00 to 1.28 produced by the above-mentioned production method It may be produced by a method comprising the step of blending with at least one refreshing agent. Alternatively, it may be produced by a method comprising combining two or more polysorbates 80 obtained by different methods and at least one refreshing agent selected from the group consisting of menthol, camphor, borneol and geraniol. . By manufacturing by such a method, the polydispersity of polysorbate 80 in the said soft contact lens composition can be made into 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, and 1 Even more preferably, it is from 0.00 to 1.22, and particularly preferably from 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 the deformation of the soft contact lens and the haze improving effect, can be more remarkably exhibited.

Also, 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. Also, 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 number average molecular weight of the polysorbate 80 in the above-described range, the effects of the present invention, such as the effect of suppressing the deformation of the soft contact lens and the haze improving effect, can be more prominent.
In addition, the measuring method and calculation method of a weight average molecular weight, a number average molecular weight, and polydispersion degree are as mentioned later.

The content of the polysorbate 80 in the composition is appropriately set according to the use of the composition, the form of preparation and the like, but the total amount of polysorbate 80 is usually 0.0001 to 8 w relative to the total amount of the composition. %, 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 range as described above, the effects of the present invention, such as the effect of suppressing the deformation of the soft contact lens and the haze improving effect, 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, which may be any of d-form, l-form and dl-form. Preferably, it is l-menthol, d-camphor, dl-camphor, d-borneol. Moreover, you may contain as a part of essential oil component. The above-mentioned refreshing agents may be used alone or in combination of two or more.

The content of the above-mentioned refreshing agent in the composition is appropriately set according to the use of the composition, the form of preparation and the like, but usually 0.0001 w / v% to 0. 0% of the total amount of the above composition. It is preferably 5 w / v%, more preferably 0.001 w / v% to 0.1 w / v%.
By setting the content of the refreshing agent in the range as described above, the effects of the present invention, such as the effect of suppressing the deformation of the soft contact lens and the haze improving effect, can be more remarkably exhibited.

The content ratio of the refreshing agent and the polysorbate 80 is not particularly limited, but it is preferable to contain 0.5 to 100 parts by weight of the polysorbate 80 with respect to 1 part by weight of the refreshing agent, with respect to 1 part by weight of the refreshing agent It is more preferable to contain 1 to 100 parts by weight of polysorbate 80, and it is further preferable to contain 2 to 50 parts by weight of polysorbate 80 with respect to 1 part by weight of the refreshing agent.
The ratio between the content of the refreshing agent and the value of the polydispersity of polysorbate 80 is not particularly limited, but the polydispersity of polysorbate 80 is preferably 15 to 2000 with respect to 1 part by weight of the refreshing agent. The polydispersity of polysorbate 80 is more preferably 20 to 1900 with respect to the parts by weight.
By setting the content ratio of polysorbate 80 to the refreshing agent and the ratio of the polydispersity value of polysorbate 80 to the content of the refreshing agent in the above-mentioned range, the adsorption of the refreshing agent to SCL and irritation to eyes And the like, and the effects of the present invention, such as the effect of suppressing the deformation of the soft contact lens and the effect of improving the haze, can be exhibited more remarkably.

  The above composition is applicable to any soft contact lens known in the art. The term "soft contact lens" (SCL) as used herein refers to a soft contact lens as opposed to a hard contact lens having a hard feel. As a method of classifying soft contact lenses, there is a method of classifying soft contact lenses described in ISO 18369-1: 2006 and ISO 18369-1: AMENDMENT 1. For example, SCL belonging to group I has as a common property that the water content is less than 50% and the molar percentage of the monomer having an anion among the constituent monomers of the raw material polymer is less than 1%.

  Also known are silicone hydrogel contact lenses in which a hydrophilic monomer (eg, hydroxyethyl methacrylate, dimethyl acrylamide, etc.) is copolymerized with a silicone-containing material (eg, TRIS or TRIS derivative, which is a polymer of silicone and acrylate, etc.). ing. Examples of names of materials based on USAN (United State Adopted Name) of silicone hydrogel contact lenses include Lotrafilcon A, Lotrafilcon B, Balafilcon A, Galyfilcon A, Senofilcon A, Narafilcon A, Comfilcon A and the like.

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

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

Various molecular weight measurement methods such as liquid chromatography, ultracentrifugation, light scattering, and limiting viscosity method are known as methods for measuring molecular weight. Depending on the difference in measurement method, the type of average molecular weight obtained such as weight average molecular weight and number average molecular weight, and the range of measurable molecular weight differ. The polydispersity defined in the present invention is measured by size exclusion chromatography (SEC). The SEC method can measure weight average molecular weight, number average molecular weight, and polydispersity, and is easy to operate. Therefore, the SEC method is most widely used for the measurement of polymer compounds, oligomers and the like. The SEC method uses a column with a gel having pores as a filler, and has a mechanism in which separation occurs due to differences in elution time due to differences in migration 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 generated by a standard substance of known molecular weight. As described above, the polydispersity obtained by the SEC method is a relative value obtained by performing molecular weight calibration using a standard substance, and thus is a value obtained only by performing under the same conditions. Therefore, as described later, the SEC method of the present invention is defined as using polyethylene oxide and polyethylene glycol as standard substances. Also, because they are relative values, setting of conditions in separation of test components and preparation of a calibration curve is also important. In view of the characteristics of these SEC methods, the present inventors diligently studied the measurement conditions of the SEC method in order to enhance the accuracy of the polydispersity calculation of polysorbate 80.

In the present embodiment, the weight average molecular weight, number average molecular weight and polydispersity of polysorbate 80 in the composition for soft contact lens are measured as follows.
(Preparation of calibration curve solution)
1. Polyethylene oxide (Tosoh Corp.) and polyethylene glycol (Wako Pure Chemical Industries, Ltd.) having molecular weights of several hundred thousand to several hundreds are used as standard substances. Polyethylene oxide and polyethylene glycol as standard substances have three molecular weights of several hundred thousand, two of several tens of thousands of molecular weight, two of several thousand molecular weight, and several hundred molecular weight It is preferable to use one kind of one. More preferably, polyethylene oxide of molecular weight 580000, 255000, 146000, 44900, 27000 and polyethylene glycol of molecular weight 8000, 1000, 600 are used, divided into molecular weight 580000, 146000, 27000, 1000 and molecular weight 255000, 44900, 8000, 600 , Combine so that elution positions do not overlap.
2. Prepare an aqueous solution in which the concentration of the standard substance is 0.1 w / v%, and use this as the 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. Correctly take 1.0 mL of the standard solution, and use 4.0 mL of methanol as the standard solution.
(Preparation of sample solution)
4. Take exactly 1.0 mL of the test solution, and use 4.0 mL of methanol as the sample solution.
(Measurement by liquid chromatograph)
5. Each calibration curve solution and sample solution are measured by liquid chromatograph (Agilent 1200 series, manufactured by Agilent Technologies).
6. The columns are manufactured by Tosoh Corporation, and TSK-Gelα-4000 (exclusion limit molecular weight about 400,000) and TSK-Gelα-2500 (exclusion limit molecular weight about 5000) filled with hydrophilic vinyl polymer (inner diameter 7.8 mm for both columns) 300 mm in length) are connected and installed one by one in this order. The column temperature is 40.0 ° C. Keeping the temperature constant at 40.0 ° C. is very important to suppress the relative standard deviation of the polydispersity.
7. As the eluent, a mixed solution in which the volume of methanol is 4.0 times that of 0.10 mol / L sodium chloride TS is prepared and used for each measurement. It is very important to include sodium chloride in the eluent in order to suppress interactions between sample molecules or sample molecules and the filler, 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 are measured in order, and the analysis cycle is 60 minutes for the calibration curve solution and 90 minutes for the sample solution. Continuous measurement of the calibration curve solution and the sample solution without interrupting the measurement is very important 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 weight average molecular weight and number average molecular weight are calculated for the range between the chromatogram curve and the baseline. The elution time and molecular weight value of each peak are plotted from the calibration curve solution, and approximation by a linear equation is performed to obtain a calibration curve, and the correlation coefficient is 0.99 or more. Furthermore, in order to reduce errors in analysis processing of chromatograms, the obtained peaks are vertically divided at intervals of 0.1 minutes or more and less than 0.001 minutes, and the average molecular weight is calculated.
13. The polydispersity is calculated from the equation M _w / M _n . Above 4. The sample solution of the process shown in is measured three times, and the average value of the polydispersity determined in each is adopted as the polydispersity of the present application.

The relative standard deviation of the average molecular weight in the commonly known SEC method is about 4 to 5% as calculated by the following formula A and formula B. Since the relative standard deviation of the polydispersity is less than 5% under the SEC measurement conditions described above, 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%. If the aforementioned reagents, columns, liquid chromatographs, etc. are not available, measurements can be made using equivalent alternatives. However, it is necessary to measure so that the relative standard deviation of polydispersity is less than 5%. In the case of a relative standard deviation of 5% or more, it is necessary to suppress the relative standard deviation within the examination range of the measurement conditions usually performed. In order to suppress the relative standard deviation in the study of the present inventors, it is important that the above conditions be satisfied for the standard substance concentration, the column temperature, the composition of the eluent and the analysis cycle of the calibration curve solution and the sample solution The

The composition for soft contact lens according to the present embodiment may contain various pharmacologically active ingredients and physiologically active ingredients in appropriate amounts in addition to the above components as long as the effects of the present invention are not impaired. Such ingredients are not particularly limited, and may be, for example, an active ingredient in an ophthalmic drug described in General Pharmaceutical Production (Import) Approval Standard 2000 Edition (Supervised by Pharmaceutical Review Research Committee). Specifically, as components used in ophthalmic drugs, the following components may be mentioned.
Antihistamines: diphenhydramine hydrochloride, chlorpheniramine maleate, etc.
Decongestants: tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline nitrate, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, methyl ephedrine hydrochloride and the like.
Vitamins: Flavin adenine dinucleotide sodium, cyanocobalamin, retinol acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, calcium pantothenate, sodium pantothenate, tocopherol acetate and the like.
Amino acids: potassium aspartate, magnesium aspartate, aminoethyl sulfonic acid and the like.
Anti-inflammatory agent: Dipotassium glycyrrhizinate, allantoin, ε-aminocaproic acid, berberine chloride, berberine sulfate, lysozyme chloride, azulene sulfonate sodium and the like.
Astringent: zinc flower, zinc lactate, zinc sulfate etc.
Others: Sodium hyaluronate, sodium chondroitin sulfate, sulfamethoxazole, sulfamethoxazole sodium, sulfisoxazole, sulfisomidine sodium, neostigmine methylsulfate, alginic acid and the like.

In the composition for soft contact lens according to the present embodiment, various additives are appropriately selected according to the usual method according to the application and the form, as long as the effects of the invention are not impaired. An appropriate amount may be contained in combination with the above. As those additives, for example, various additives described in Pharmaceutical Additives Dictionary 2007 (edited by Japan Pharmaceutical Additives Association) can be exemplified. The following additives are mentioned as a typical component.
Carrier: aqueous carrier such as water, hydrous ethanol and the like.
Thickener: hydroxypropyl methylcellulose, polyvinyl pyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, sodium chondroitin sulfate, hydroxyethylcellulose, methylcellulose, carboxymethylcellulose sodium and the like.
Sugars: glucose, cyclodextrin, etc.
Sugar alcohols: xylitol, sorbitol, mannitol, glycerin and the like. These may be d-form, l-form or dl-form.
Antiseptics, fungicides or antibacterial agents: alkyl polyaminoethyl glycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, parahydroxybenzoic acid Ethyl acid, propyl parahydroxybenzoate, butyl parahydroxybenzoate, phenethyl alcohol, benzyl alcohol, polyhexamethylene biguanide, chlorhexidine gluconate and the like.
Buffer: boric acid, aminoethyl sulfonic acid, epsilon-aminocaproic acid, sodium citrate, polyethylene glycol, propylene glycol, sodium bisulfite, sodium sulfite, sodium chloride, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, disodium hydrogen phosphate , Sodium dihydrogen phosphate, potassium dihydrogen phosphate etc.
pH adjuster: hydrochloric acid, boric acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium hydrogencarbonate, sodium carbonate, sodium carbonate, borax, triethanolamine, monoethanolamine, diisopropanol Amine etc.
Stabilizers: dibutyl hydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (long gallite), tocopherol, sodium metabisulfite, monoethanolamine, aluminum monostearate, glycerin monostearate and the like.
Chelating agents: ascorbic acid, tetrasodium edetate, sodium edetate, citric acid and the like.
Fragrances or refreshing agents other than those mentioned above: anethole, eugenol, cineole, limonene, leunow and the like. These may be either d-, l- or dl and may be formulated as essential oils (mint oil, coolmint oil, spearmint oil, peppermint oil, peppermint oil, fennel oil, caffeine oil, bergamot oil, eucalyptus oil, rose oil etc) You may

  The composition for soft contact lens according to the present embodiment can take various formulation 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. Preferably it is a solution, more preferably an aqueous solution. Here, the aqueous solution means a solution containing water, and usually 75% by weight or more, preferably 80% by weight or more, more preferably 85% by weight or more, more preferably 90% by weight of water in the composition. It means what contains more than%. The water contained in the aqueous solution may be pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. For example, distilled water, normal water, purified water, sterile purified water, water for injection, distilled water for injection, etc. can be used. These definitions are based on the 16th Amended Japanese Pharmacopoeia.

  The pH of the composition for soft contact lens according to the present embodiment is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. The pH of the composition for soft contact lenses is, for example, preferably 4.0 to 9.5, more preferably 5.0 to 9.0, and 5.5 to 8.5. Is more preferred.

  About the osmotic pressure of the composition for soft contact lenses which concerns on this embodiment, if it is a range accept | permitted by the biological body, it will not be specifically limited. The osmotic pressure ratio of the composition for soft contact lens is, for example, preferably 0.5 to 5.0, more preferably 0.6 to 3.0, and 0.7 to 2.0. Is more preferred.

  About the viscosity of the composition for soft contact lenses which concerns on this embodiment, if it is a range accept | permitted by the biological body, it will not be specifically limited. The viscosity at 20 ° C. measured with a rotational viscometer (RE 550 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1 ° 34 ′ × 24) is preferably, for example, 0.01 to 10000 mPa · s, 0.05 It is more preferable that it is -8000 mPa * s, and it is still more preferable that it is 0.1-6000 mPa * s.

  The composition for soft contact lens according to the present embodiment is prepared by adding the above-mentioned polysorbate 80 and a refreshing agent and, if necessary, other components to a desired concentration to a carrier. For example, after combining and stirring Polysorbate 80 and a refreshing agent, it can be prepared by adding purified water, emulsifying or dissolving, adjusting to a predetermined pH and osmotic pressure, and sterilizing by filtration sterilization or the like.

  Examples of containers for the composition for soft contact lens according to the present embodiment include containers made of metal, glass or plastic. The material of the plastic container is made of polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polypropylene (PP), polyarylate (PAR), polybutylene terephthalate (PBT) or polycarbonate (PC) In any container selected from the group consisting of Preferably, it is made of PET, PEN, PP, PAR, PC or glass, more preferably of PET, PP or glass. When the container is a synthetic resin, the container may be formed of only a single synthetic resin, or may be formed by combining a plurality of synthetic resins.

  The composition for soft contact lens according to the present embodiment is not limited in its form and application as long as it is used in the ophthalmologic field and used to contact the soft contact lens. For example, eye drops for soft contact lenses (eye drops that can be used while wearing soft contact lenses), eye washes for soft contact lenses (eye wash that can be used while wearing soft contact lenses), soft contact lens mounting solution, Examples thereof include soft contact lens care solutions (soft contact lens disinfectant, soft contact lens storage solution, soft contact lens cleaning solution, soft contact lens cleaning solution, etc.).

  The composition for a soft contact lens can suppress deformation of the soft contact lens by bringing the composition into contact with the soft contact lens.

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

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

4. Method for suppressing eye blur during soft contact lens wear The method for suppressing eye blur during soft contact lens wear according to the present embodiment is selected from the group consisting of polysorbate 80 and menthol, camphor, borneol and geraniol Contacting the soft contact lens composition containing at least one refreshing agent with the soft contact lens, wherein the polydispersity of the polysorbate 80 in the soft contact lens composition is It is 1.00 to 1.28. The components, contents, and methods of measuring the degree of polydispersity and the like in the composition for a soft contact lens used in the above method, and other conditions, etc. It is the same as the composition for soft contact lenses.

5. Lens deformation inhibitor for soft contact lens The lens deformation inhibitor according to the present embodiment contains polysorbate 80 and at least one refreshing 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. The components, the content, the method of measuring the degree of polydispersion, etc. in the lens deformation inhibitor, and other conditions, etc. It is the same as the composition for soft contact lenses.

6. Eye haze inhibitor during soft contact lens wear The eye blur inhibitor during soft contact lens wear according to this 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 inhibitor is 1.00 to 1.28. The components, contents, measuring methods of polydispersity and the like in the above-mentioned eye haze inhibitor, and other conditions, etc. It is the same as the composition for soft contact lenses.

According to the present invention, by suppressing the deformation of the soft contact lens caused by the polysorbate 80, it is possible to provide a soft contact lens composition that reduces the deterioration of the fitting between the contact lens and the eye and suppresses the corneal epithelial disorder. become.
Furthermore, according to the present invention, it is possible to provide a soft contact lens composition capable of maintaining the visual acuity correction power by suppressing eye blur during wearing of the soft contact lens.

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

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

  The test solutions described in Table 2 were prepared using polysorbate 80 different in polydispersity described in Table 1. The thing containing a in a test liquid name shows the test liquid containing refreshing agents, such as l-menthol, and the thing containing b in a test liquid name shows the test liquid which does not contain refreshing agents, such as l-menthol. The lens size change was calculated by the method described later for each, and the inhibition rate of the size change was calculated using those values. For example, using the lens size change of Comparative Example 1a and Comparative Example 1b, the suppression rate of the size change of Comparative Example 1 was calculated. The polysorbate 80 in all the test solutions was measured by the aforementioned SEC measurement method, and the polydispersity was calculated and is shown in Table 2. In Table 2, the amount of each component is shown by w / v%.

(2) Evaluation of size change of soft contact lens Soft contact lens (USAN name: Galyfilcon A; water content 47.0%, nonionic, POWER-3.00, B.C. 8.7) in 10 mL of physiological saline , DIA 14.0 mm) 1 sheet each, and left still at 34 ° C. for 4 hours or more. A saline solution and a soft contact lens are transferred to a cell from a glass vial kept at a constant temperature of 34 ° C using a water bath, and the cell is filled with the saline solution. Universal Projector (Product Name: PROFILE PROTECTOR V The size (diameter) of the soft contact lens was measured by setting it to -128 (manufactured by Nikon) (start value). In addition, in order not to change the temperature of the soft contact lens, the time from removal from the water bath to measurement is shortened within about 20 seconds, and the time from removal to measurement is the same between samples. It was measured. Then, the soft contact lens whose start value was measured was immersed in 10 mL of each test solution prepared according to Table 2 and allowed to stand at 34 ° C. for 24 hours. After 24 hours, the inside of the cell was co-washed with a separately prepared test solution at 34 ° C., the test solution in the vial and the soft contact lens were transferred to the cell, and the cell size was measured in the same manner as above ( Processed value). The size change amount of the soft contact lens was calculated by subtracting the start value from the post-processing value (Equation 1). Furthermore, using the following (formula 2), the suppression ratio of the soft contact lens size change of the test liquid containing l-menthol (refining agent) to the test liquid not containing l-menthol (refining agent) was calculated. .
Lens size change (mm) = post processing value-start value (Equation 1)
Size change inhibition rate (%) = (lens size change of test solution containing no refreshing agent (mm) -lens size change of test solution containing refreshing agent (mm)) / (does not contain refreshing agent Lens size change of test solution) × 100 (Equation 2)

  FIG. 1 shows a correlation diagram between the polydispersity of polysorbate 80 in the test solution and the inhibition 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 shows a negative value, whereas the above-mentioned polydispersity is 1.26 or less In Examples 1 to 4, it was found that the inhibition rate had a positive value.

Also in the case of _Mn , it was examined whether there was a correlation with the rate of inhibition of the size change of the lens, but no significant correlation was found.

Test Example 1-2. Test on Size Change of Soft Contact Lens (1) Preparation of Composition for Soft Contact Lens The test solution described in Table 3 was prepared using polysorbate 80 different in polydispersity described in Table 1. In Table 3, the amount of each component is shown by w / v%.

(2) Evaluation of Size Change of Soft Contact Lens The change of the lens size was evaluated by the same method as in Test Example 1-1, and the suppression rate of the size change of the soft contact lens by the refreshing agent was calculated.
FIG. 1 shows a correlation diagram between the polydispersity of polysorbate 80 in the test solution and the inhibition rate of lens size change by d-camphor (squares 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 above-mentioned polydispersity is 1.26 or less. In 6, it was found that the inhibition rate showed a positive value. That is, even when the combined refreshing agent was d-camphor, it showed the same behavior as menthol.

Test Example 1-3. Test on Size Change of Soft Contact Lens (1) Preparation of Composition for Soft Contact Lens The test solution described in Table 4 was prepared using polysorbate 80 different in polydispersity described in Table 1. In Table 4, the amount of each component is shown by w / v%.

(2) Evaluation of Size Change of Soft Contact Lens The change of the lens size was evaluated by the same method as in Test Example 1-1, and the suppression rate of the size change of the soft contact lens by the refreshing agent was calculated.
FIG. 1 shows a correlation diagram between the polydispersity of polysorbate 80 in the test solution and the inhibition rate of the lens size change by d-borneol (triangular marks in FIG. 1). In Comparative Example 5 in which the polydispersity of polysorbate 80 in the test solution is 1.29, the inhibition rate shows a negative value, whereas the above-mentioned polydispersity is 1.26 or less. In 8, it was found that the inhibition rate had a positive value. That is, even when d-borneol was used as the refreshing agent to be combined, it showed the same behavior as menthol and d-camphor.

Test Example 2 Evaluation of eye blur while wearing soft contact lens Soft contact lens (ISO 18369-1: 2006 and ISO 18369-1: any one of Group I, IV, V in the classification method of soft contact lens described in AMENDMENT 1) VAS method using a 10 cm straight line with a scale of 0 to 100 shown in Table 6, in which 1 person wearing 1 to 2 drops of the formulated solution shown in Table 5 once a day with 5 drops of 5 persons wearing Eye blur was evaluated by (Visual Analog Scale). In Table 5, the amount of each component is shown by w / v%. The eye drop was given five times a day, and the next instillation was performed after a sufficient time after one instillation. The average score of the haze evaluation of 5 persons is shown in Table 5.

  Table 5 shows the results of the eye haze evaluation. In Comparative Examples 6 and 7 in which the polydispersity of polysorbate 80 in the test solution is 1.29 or more, while the haze which feels unpleasant is produced, the above-mentioned polydispersity is 1.26 or less. It turned out that No. 9 and 10 did not produce a haze.

Claims (1)

Polysorbate 80, mosquitoes Nfuru, a soft contact lens deformation suppressing agent comprising at least one cooling agent selected from the group consisting of borneol and geraniol,
2 to 5 parts by weight of the polysorbate 80 relative to 1 part by weight of the refreshing agent,
The degree of polydispersity represented by weight average molecular weight / number average molecular weight of the polysorbate 80 in the soft contact lens deformation inhibitor is 1.00 to 1.26, and the weight average molecular weight and the number average molecular weight exclude size A soft contact lens deformation inhibitor which is measured by a chromatography method.

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