JP5595206B2 - Ophthalmic liquid composition - Google Patents

Description

  The present invention relates to an ophthalmic liquid composition containing a polymer having a phosphorylcholine-like group in a side chain. More specifically, the present invention includes a polymer having a phosphorylcholine-like group in the side chain, but when the liquid is dropped from the nozzle, the liquid is easily drained and remains on the outer surface of the nozzle after the dropping (liquid remaining). The present invention relates to an ophthalmic liquid composition that is difficult to perform. The present invention also relates to an ophthalmic liquid composition for soft contact lenses that can suppress adhesion of microorganisms to the soft contact lens.

  A polymer having a phosphorylcholine-like group in the side chain is known as a compound having high biocompatibility. In addition, the polymer is known to be effective for skin care because it has functions such as keratin protection and moisture retention (see Patent Document 1). Furthermore, it has been found that the polymer is effective in prevention or treatment of dry eye (see Patent Document 2) and improvement in retention of active ingredients (see Patent Document 3) in the ophthalmic field.

  Thus, the polymer has not only biocompatibility but also various pharmacological actions, and has attracted attention as a functional material. In particular, in recent years, the use of the polymer in the field of ophthalmology has been actively attempted, and the formulation of an ophthalmic liquid composition containing the polymer has been reported (see Patent Documents 4-5).

  On the other hand, ophthalmic liquid compositions such as eye drops are generally used by being contained in a container configured to allow droplets to be dropped from a nozzle by pressing against the container. For this reason, it is important to provide the ophthalmic liquid composition with physical properties such that liquid drops are good when dripped from the nozzle, and it does not remain (liquid residue) on the outer surface of the nozzle.

  However, at present, the ophthalmic liquid composition containing the polymer has not been sufficiently studied for compatibility with the container to be accommodated.

  In recent years, the number of wearers of soft contact lenses has increased. Soft contact lenses are comfortable to wear, but because the material contains water, microorganisms are easy to grow and usually require disinfection. However, disinfection is often incomplete due to reasons such as non-compliance, and infectious diseases caused by microorganisms are a problem.

JP 9-52848 A Japanese Patent Laid-Open No. 10-324634 JP 11-335301 A JP 2008-273959 A JP 7-166154 A

  As a result of repeated studies on the physical properties of an ophthalmic liquid composition containing a polymer having a phosphorylcholine-like group in the side chain, the ophthalmic liquid composition containing the polymer is dropped from a nozzle. At that time, a new problem was found in that the liquid was not easily drained and the liquid was likely to remain on the outer surface of the nozzle after dropping. As described above, when the ophthalmic liquid composition remains on the outer surface of the nozzle after the dripping, there is a possibility of causing contamination such as adhesion of foreign substances and propagation of germs through the remaining liquid. It is not preferable because the ophthalmic liquid composition may be dropped through the contaminated nozzle. Furthermore, the remaining ophthalmic liquid composition components are deposited on the outer surface of the nozzle or the ophthalmic liquid composition is dripped from the nozzle onto the surface of the container. There is also a concern that it will be damaged. Further, when the liquid from the nozzle is poorly discharged, a part of the ophthalmic liquid composition or deposits exposed to the environment outside the container at the time of dropping flows back into the container, and thereby the ophthalmic liquid composition in the container. It also increases the risk of foreign objects and bacteria entering the object. In particular, in the case of eye drops, there is a problem in that the amount of drops to be instilled varies and the applied amount of the drug varies when the liquid is excessively poor.

  Therefore, the present invention is for ophthalmology that contains a polymer having a phosphorylcholine-like group in the side chain, and that when the solution is dropped from the nozzle, it is easily drained and does not easily remain on the outer surface of the nozzle after the dropping. An object is to provide a liquid composition.

  Another object of the present invention is to provide an ophthalmic liquid composition for soft contact lenses that can suppress the adhesion of microorganisms to the surface of the soft contact lens.

  As a result of intensive studies to solve the above problems, the present inventors have surprisingly found that in the ophthalmic liquid composition, (A) a polymer having a phosphorylcholine-like group in the side chain and a specific content ratio. (B-1) Chondroitin sulfate and / or salt thereof, (B-2) Hyaluronic acid and / or salt thereof, or (B-3) Glucose is dripped from the nozzle in a specific ratio. It was found that the liquid breakage was good and the liquid did not remain on the outer surface of the nozzle after dropping. Furthermore, by coexisting (C-1) ethylenediaminetetraacetic acid and / or a salt thereof and / or (C-2) sodium chloride, liquid drainage from the nozzle is further improved, and liquid on the outer surface of the nozzle is improved. It was found that the rest could be further suppressed. Furthermore, the present inventors surprisingly, (A) a polymer having a phosphorylcholine-like group in the side chain, (B-1) chondroitin sulfate and / or a salt thereof having a specific content, (B-2) It has also been found that the combined use of hyaluronic acid and / or a salt thereof or (B-3) glucose at a specific ratio can suppress the formation of precipitates when the ophthalmic composition adheres to the edge or eyelashes of the eye. It was.

  In addition, the present inventors have confirmed that soft contact lenses (hereinafter sometimes referred to as “SCL”) have the property that bacteria are likely to adhere, and as means for solving them, (A) A combination of a polymer having a phosphorylcholine-like group in the side chain and at least one of (B) chondroitin sulfate, hyaluronic acid, salts thereof, and glucose is effective in suppressing bacterial adhesion to SCL. I also found. Further, the inventors of the present invention have also described that SCL is a combination of (A) a polymer having a phosphorylcholine-like group in the side chain and (B) at least one of chondroitin sulfate, hyaluronic acid, salts thereof, and glucose. It was found to be effective for improving the wettability of the pollen protein and the cleaning effect of the pollen protein adhering to the ionic silicone hydrogel contact lens (hereinafter sometimes referred to as “ionic SHCL”). The present invention has been completed by further studies based on this finding.

That is, this invention provides the ophthalmic liquid composition of the aspect hung up below.
Item 1-1. (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer that can be copolymerized;

[Wherein, n1 is an integer of 2 to 4, R ₁ is a hydrogen atom or a methyl group, R ₂ is a group represented by — (R ₆ O) _n2 —R ₆ — (R ₆ has 1 to 4 carbon atoms] And n2 represents an integer of 0 to 5), and R _{3 to} R ₅ are the same or different and represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. ]
(B-1) at least one of chondroitin sulfate and a salt thereof, (B-2) at least one of hyaluronic acid and a salt thereof, or (B-3) glucose.
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
The content ratio of the component (B-3) is 0.005 to 0.2 w / v%, and the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more, Ophthalmic liquid composition.
Item 1-2. The component (A) is a polymer of a monomer represented by the general formula (I), or a copolymer of a monomer represented by the general formula (I) and a monomer represented by the following general formula (II). Item 1. An ophthalmic liquid composition according to Item 1-1.

[Wherein, R ₇ represents a hydrogen atom or a methyl group, and R ₈ represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms. ]
Item 1-3. Item 1. The ophthalmic liquid composition according to Item 1-1 or 1-2, wherein the component (A) is a copolymer of 2-methacryloyloxyethyl phosphorylcholine and butyl methacrylate.
Item 1-4. Item 4. The ophthalmic liquid composition according to any one of Items 1-1 to 1-3, wherein the content of component (A) is 0.0001 to 5 w / v%.
Item 1-5. Item 5. The ophthalmic liquid composition according to any one of Items 1-1 to 1-4, further comprising (C-1) at least one selected from the group consisting of ethylenediamineacetic acid, derivatives thereof, and salts thereof.
Item 1-6. Item 5. The ophthalmic liquid composition according to Item 1-5, which contains at least one selected from the group consisting of ethylenediamineacetic acid and salts thereof as the component (C-1).
Item 1-7. Item 5. The ophthalmic liquid composition according to Item 1-5 or 1-6, wherein the content of component (C-1) is 0.0005 to 0.2 w / v%.
Item 1-8. The ophthalmic liquid composition according to any one of Items 1-1 to 1-7, further comprising sodium chloride as the component (C-2).
Item 1-9. Item 9. The ophthalmic liquid composition according to Item 1-8, wherein the content ratio of the component (C-2) is 0.01 to 10 w / v%.
Item 1-11. Item 11. The ophthalmic liquid composition according to any one of Items 1-1 to 1-10, which is contained in a container equipped with a polyethylene nozzle.
Item 1-12. Item 12. The ophthalmic liquid composition according to any one of Items 1-1 to 1-11, wherein the ophthalmic liquid composition is an eye drop and is contained in an eye drop container equipped with a polyethylene nozzle.

Moreover, this invention provides the ophthalmic liquid composition for SCL of the aspect hung up below.
Item 2-1. (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer that can be copolymerized;

[Wherein, n1 is an integer of 2 to 4, R ₁ is a hydrogen atom or a methyl group, R ₂ is a group represented by — (R ₆ O) _n2 —R ₆ — (R ₆ has 1 to 4 carbon atoms] And n2 represents an integer of 0 to 5), and R _{3 to} R ₅ are the same or different and represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. ]
(B) An ophthalmic liquid composition for soft contact lenses comprising chondroitin sulfate, hyaluronic acid, salts thereof, and at least one of glucose.
Item 2-2. The component (A) is a polymer of a monomer represented by the general formula (I), or a copolymer of a monomer represented by the general formula (I) and a monomer represented by the following general formula (II). The ophthalmic liquid composition for soft contact lenses according to Item 2-1.

[Wherein, R ₇ represents a hydrogen atom or a methyl group, and R ₈ represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms. ]
Item 2-3. Item 3. The ophthalmic liquid composition for soft contact lenses according to Item 2-1 or 2-2, wherein the component (A) is a copolymer of 2-methacryloyloxyethyl phosphorylcholine and butyl methacrylate.
Item 2-4. Item 4. The ophthalmic liquid composition for soft contact lenses according to any one of Items 2-1 to 2-3, wherein the content ratio of the component (A) is 0.0001 to 5 w / v%.
Item 2-5. Item 5. The ophthalmic liquid composition for soft contact lenses according to any one of Items 2-1 to 2-4, wherein the content ratio of the component (B) is 0.0002 to 1.5 w / v%.
Item 2-6. Item 5. The ophthalmic liquid composition for soft contact lenses according to any one of Items 2-1 to 2-5, comprising 0.1 to 50000 parts by weight of the total amount of the component (B) per 100 parts by weight of the total amount of the component (A) .
Item 2-7. Item 5. The ophthalmic liquid composition for soft contact lenses according to any one of Items 2-1 to 2-6, further comprising a borate buffer.
Item 2-8. Item 8. The ophthalmic liquid composition for soft contact lenses according to Item 2-7, wherein the borate buffer is boric acid and / or borax.
Item 2-9. Item 9. The ophthalmic liquid composition for soft contact lenses according to Item 2-7 or 2-8, wherein the borate buffer content is 0.1 to 5 w / v%.
Item 2-10. The ophthalmic ophthalmic soft contact lens according to any one of Items 2-1 to 2-9, further comprising (C-1) at least one selected from the group consisting of ethylenediamineacetic acid, derivatives thereof, and salts thereof. Liquid composition.
Item 2-11. Item 10. The ophthalmic liquid composition for soft contact lenses according to Item 2-10, which contains at least one selected from the group consisting of ethylenediamineacetic acid and salts thereof as the component (C-1).
Item 2-12. The ophthalmic liquid composition for soft contact lenses according to Item 2-10 or 2-11, wherein the content ratio of component (C-1) is 0.0005 to 0.2 w / v%.
Item 2-13. The ophthalmic liquid composition for soft contact lenses according to any one of Items 2-1 to 2-12, further comprising sodium chloride as a component (C-2).
Item 2-14. Item 14. The ophthalmic liquid composition for soft contact lenses according to Item 2-13, wherein the content ratio of the component (C-2) is 0.01 to 10 w / v%.
Item 2-15. Item 15. The ophthalmic liquid composition for soft contact lenses according to any one of Items 2-1 to 2-14, which is an eye drop for soft contact lenses or a mounting solution for soft contact lenses.
Item 2-16. Item 16. The ophthalmic liquid composition for soft contact lenses according to any one of Items 2-1 to 2-15, which is contained in a container equipped with a polyethylene nozzle.
Item 2-17. The soft contact lens ophthalmic liquid composition is an eye drop for soft contact lens, and the soft medicine according to any one of Items 2-1 to 2-16, which is housed in an eye drop container equipped with a polyethylene nozzle. An ophthalmic liquid composition for contact lenses.

Furthermore, this invention provides the method of the following aspect.
Item 3-1. In the ophthalmic liquid composition, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B-1) chondroitin sulfate and a salt thereof At least one, (B-2) at least one of hyaluronic acid and its salt, or (B-3) glucose.
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
(B-3) The content ratio of the component is 0.005 to 0.2 w / v%, and it is used in combination so that the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more. A method for improving the drainage of an ophthalmic liquid composition from a nozzle.
Item 3-2. (A) To an ophthalmic liquid composition containing a polymer obtained by polymerizing a monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, (B-1) in chondroitin sulfate and salts thereof At least one, (B-2) at least one of hyaluronic acid and its salt, or (B-3) glucose.
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
(B-3) The content ratio of the component is 0.005 to 0.2 w / v%, and the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more. A method for improving the drainage of an ophthalmic liquid composition from a nozzle.
Item 4-1. In the ophthalmic liquid composition, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B-1) chondroitin sulfate and a salt thereof At least one, (B-2) at least one of hyaluronic acid and its salt, or (B-3) glucose.
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
(B-3) The content ratio of the component is 0.005 to 0.2 w / v%, and it is used in combination so that the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more. A method for improving the liquid residue of an ophthalmic liquid composition on a nozzle.
Item 4-2. (A) To an ophthalmic liquid composition containing a polymer obtained by polymerizing a monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, (B-1) in chondroitin sulfate and salts thereof At least one, (B-2) at least one of hyaluronic acid and its salt, or (B-3) glucose.
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
(B-3) The content ratio of the component is 0.005 to 0.2 w / v%, and the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more. A method for improving the liquid residue of an ophthalmic liquid composition on a nozzle.
Item 5-1. In the ophthalmic liquid composition, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B-1) chondroitin sulfate and a salt thereof At least one, (B-2) at least one of hyaluronic acid and its salt, or (B-3) glucose.
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
(B-3) The content ratio of the component is 0.005 to 0.2 w / v%, and it is used in combination so that the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more. A method for suppressing the formation of precipitates of an ophthalmic liquid composition comprising the component (B-1), the component (B-2), or the component (B-3), which is characterized.
Item 5-2. (B-1) 0.05 to 0.5 w / v% of at least one of chondroitin sulfate and its salt, (B-2) 0.002 to 0.1 w / v% of at least one of hyaluronic acid and its salt, Or (B-3) polymerizing ophthalmic liquid composition containing glucose in an amount of 0.005 to 0.2 w / v%, with (A) the monomer represented by the general formula (I) alone or copolymerizable with another monomer The polymer
The ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
(A) The ratio of component (B-2) to 100 parts by weight of component is 0.1 parts by weight or more, or
(B) component, (B-2) component, or (B), characterized in that the ratio of component (B-3) to 100 parts by weight of component (A) is 1 part by weight or more. -3) A method for suppressing the formation of precipitates of an ophthalmic liquid composition containing a component.
Item 6. (A) a polymer obtained by polymerizing the monomer represented by formula (I) alone or with another copolymerizable monomer, and (B) at least one of chondroitin sulfate, hyaluronic acid, a salt thereof, and glucose A method for inhibiting bacterial adhesion to SCL, comprising contacting an ophthalmic liquid composition containing a seed with SCL.
Item 7. In the ophthalmic liquid composition, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B) chondroitin sulfate, hyaluronic acid, a salt thereof, And a method of imparting to the ophthalmic liquid composition an action of inhibiting bacterial adhesion to SCL, comprising using at least one of glucose and glucose.
Item 8. (A) a polymer obtained by polymerizing the monomer represented by formula (I) alone or with another copolymerizable monomer, and (B) at least one of chondroitin sulfate, hyaluronic acid, a salt thereof, and glucose A method for improving the wettability of SCL, comprising bringing an ophthalmic liquid composition containing seeds into contact with SCL.
Item 9. In the ophthalmic liquid composition, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B) chondroitin sulfate, hyaluronic acid, a salt thereof, And a method for imparting to the ophthalmic liquid composition an action for improving the wettability of SCL, which comprises using at least one of glucose and glucose.
Item 10. (A) a polymer obtained by polymerizing the monomer represented by formula (I) alone or with another copolymerizable monomer, and (B) at least one of chondroitin sulfate, hyaluronic acid, a salt thereof, and glucose A method for washing pollen protein adhering to an ionic silicone hydrogel contact lens, comprising contacting an ophthalmic liquid composition comprising a seed with the ionic silicone hydrogel lens.
Item 11. In the ophthalmic liquid composition, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B) chondroitin sulfate, hyaluronic acid, a salt thereof, And a method of imparting to the ophthalmic liquid composition a cleaning action on pollen protein adhering to an ionic silicone hydrogel contact lens, wherein at least one of glucose and glucose is used in combination.

  According to the present invention, an ophthalmology that contains a polymer having a phosphorylcholine-like group in the side chain, but that drains well when dropped from a nozzle and does not easily remain (liquid residue) on the external surface of the nozzle after dropping. A liquid composition can be provided. As a result, contamination of foreign matters, bacterial contamination, and the like can be suppressed. Therefore, the ophthalmic liquid composition of the present invention has a reduced risk of contamination, excellent quality retention, and is extremely useful from a practical viewpoint. It is.

  In addition, since the ophthalmic liquid composition of the present invention can suppress the formation of precipitates when adhering to the edge or eyelash of the eye, even if it adheres to the edge or eyelash of the eye during use, It does not impair the appearance and is convenient for the user.

  Furthermore, according to the ophthalmic liquid composition of the present invention, since the adhesion of bacteria to SCL can be suppressed, the risk of microbial infection caused by wearing SCL can be reduced, and SCL can be used more safely. Become.

  Furthermore, according to the ophthalmic liquid composition of the present invention, the wettability of SCL can be improved, so that the wearing feeling of SCL can be improved and the discomfort during wearing of SCL can be reduced.

  In addition, the present inventors have found that pollen proteins are often attached to ionic SHCL among SCLs, but according to the ophthalmic liquid composition of the present invention, pollen proteins attached to ionic SHCL are also present. The ionic SHCL can be kept clean by using the ophthalmic liquid composition of the present invention during or before or after wearing the ionic SHCL. The risk of developing symptoms can be reduced.

In Test Example 1A, it is a figure which shows the result of having measured the nozzle adhesion liquid amount after 20 drops of test liquid (Comparative Examples 1-1 to 1-4) dripping. That is, FIG. 1 is a diagram showing the result of comparative evaluation of the influence of the MPC polymer on the nozzle adhesion liquid amount. The figure which shows the result of having measured the nozzle adhesion liquid amount after 20 drops of test liquid (Example 1-1, 1-6, 1-7, and comparative examples 1-3-1-6) in Test Example 1A. It is. That is, FIG. 2 is a diagram showing the results of comparative evaluation of the influence of the combination of MPC polymer and sodium chondroitin sulfate on the amount of nozzle adhesion liquid. In Test Example 1A, after dropping 20 drops of the test solution (Examples 1-2 to 1-4, 1-8, 1-9, Comparative Examples 1-3, 1-4, 1-7, and 1-8) It is a figure which shows the result of having measured the nozzle adhesion liquid amount. That is, FIG. 3 is a diagram showing the results of comparative evaluation of the effect of the combination of MPC polymer and sodium hyaluronate on the amount of nozzle adhesion liquid. In Test Example 1A, the amount of nozzle adhesion liquid after 20 drops of the test liquid (Examples 1-5, 1-10, 1-11, and Comparative Examples 1-3, 1-4, and 1-9) was measured. It is a figure which shows a result. That is, FIG. 4 is a diagram showing the result of comparative evaluation of the influence of the combination of MPC polymer and glucose on the amount of nozzle adhesion liquid. In Test Example 3A, it is a figure which shows the result of having measured the adhesion bacteria number of Pseudomonas aeruginosa with respect to SCL processed with the test liquid (Examples 3-1 to 3-2 and Comparative Examples 3-1 to 3-4). In Test Example 4, it is a figure which shows the result of having measured the contact angle of SCL processed with the test liquid (Example 4-1 and Comparative Examples 4-1 to 4-3). In the reference test example 3, it is a figure which shows the result of having measured the cleaning effect of the pollen protein with respect to various SCL.

1. Ophthalmic liquid composition-1
The ophthalmic liquid composition-1 of the present invention is a polymer obtained by polymerizing a monomer represented by the following general formula (I) with another monomer that can be copolymerized alone or copolymerized (hereinafter referred to simply as “component (A)”). In some cases).

  In general formula (I), n1 represents an integer of 2 to 4, preferably 2 or 3, and more preferably 2.

In general formula (I), R ₁ represents a hydrogen atom or a methyl group, preferably a methyl group.

Further, in the general formula _{(I), R 2} is - shows a group represented by _{- (R 6 O) n2 -R} 6. Here, R < ₆ > shows a C1-C4 alkylene group. Specific examples of such an alkylene group include a methylene group, an ethylene group, a propylene group, and a butylene group. R ₆ is preferably an alkylene group having 1 to 3 carbon atoms, more preferably an alkylene group having 2 carbon atoms (ethylene group). N2 represents an integer of 0 to 5, preferably an integer of 0 to 2, and more preferably 0.

Moreover, in general formula (I), R < ₃ > -R < ₅ > is the same or different and shows a hydrogen atom and a C1-C4 alkyl group. Examples of such an alkyl group include a methyl group, an ethyl group, an n-propyl group, and an n-butyl group. As R < ₃ > -R < ₅ >, Preferably, a hydrogen atom or a C1-C2 alkyl group, More preferably, a C1-C1 alkyl group (methyl group) is mentioned.

Formula Preferable examples of the monomer represented by (I), 2-methacryloyloxyethyl phosphorylcholine (MPC; n1 is 2, _{R 1} is methyl, _{R 2} is an ethylene _group, R 3 to R ₅ is a methyl group) , 2-methacryloyloxyethyl phosphoryl ethanolamine (MPE; n1 is 2, _{R 1} is methyl, _{R 2} is an ethylene _group, R 3 to R ₅ is a hydrogen atom), particularly preferably exemplified 2-methacryloyloxyethyl phosphorylcholine The

  In the ophthalmic liquid composition-1 of the present invention, the component (A) is a polymer of a monomer represented by the above general formula (I) (hereinafter sometimes simply referred to as “monomer (I)”). It may be a copolymer of monomer (I) and another monomer, and further, a polymer of monomer (I) and a copolymer of monomer (I) and another monomer. It may be a mixture.

  When a copolymer is used as the component (A), as a monomer other than the monomer (I), the finally obtained copolymer is pharmaceutically, pharmacologically (pharmaceutically) or physiologically. Although it does not restrict | limit as long as it is accept | permitted, As a suitable example, the monomer (henceforth only described as "monomer (II)") represented by the following general formula (II) is illustrated.

In the general formula (II), R ₇ represents a hydrogen atom or a methyl group, preferably a methyl group.

In general formula (II), R ₈ represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms. Examples of such an alkyl group include a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, and an n-hexyl group. R ₈ is preferably an alkyl group having 1 to 5 carbon atoms, more preferably an alkyl group having 1 to 4 carbon atoms, and particularly preferably an alkyl group having 4 carbon atoms (n-butyl group).

Preferred examples of monomer (II) include butyl methacrylate (BMA; R ₇ is methyl group, R ₈ is n-butyl group), methyl methacrylate (MMA; R ₇ is methyl group, R ₈ is methyl group), 2- Hydroxyethyl methacrylate (HEMA; R ₇ is methyl group, R ₈ is hydroxyethyl group); more preferably, 2-hydroxyethyl methacrylate, butyl methacrylate; and particularly preferably butyl methacrylate.

When monomer (II) can take the form of a salt (for example, when R ₇ is a hydrogen atom), monomer (II) may be a salt. Examples of the salt form of monomer (II) include alkali metal salts such as sodium and potassium.

  When using a copolymer as the component (A), the composition ratio of the monomer (I) and other monomers varies depending on the structure of the monomer used, etc., but effectively exerts a preventive or therapeutic effect on dry eye. From the viewpoint, the monomer (I) is usually 50 to 95 mol%, preferably 60 to 90 mol%, more preferably 75 to 85 mol%, based on the total amount of the copolymer.

  In addition, the molecular weight of the polymer used as the component (A) varies depending on the type of monomer, etc., and is limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. However, for example, the weight average molecular weight is 5,000 to 2,000,000, preferably 40,000 to 1,200,000, more preferably 100,000 to 1,000,000, and particularly preferably 400,000 to 800,000. The weight average molecular weight is measured by GPC analysis.

  Monomer (I) and monomer (II) are known compounds or known methods from known compounds (for example, JP-A-58-154591, JP-A-60-184093, polymer articles) Vol.35, 423-427, 1978, published by the Society of Polymer Science, Japan).

  The polymer used as the component (A) can be obtained by polymerizing the monomer (I) and, if necessary, other monomers according to a known method in the field of polymer chemistry. Specifically, the polymerization reaction is carried out in the presence of a polymerization initiator in an appropriate solvent such as water, methanol, ethanol, propanol, t-butanol, benzene, toluene, dimethylformamide, tetrahydrofuran, chloroform, or a mixed solvent thereof. The polymerization may be performed for a certain period of time under appropriate temperature conditions.

  In the ophthalmic liquid composition-1 of the present invention, among the components (A), a polymer of monomer (I), a copolymer of monomer (I) and monomer (II); more preferably MPC or MPE polymer, MPC or MPE and HEMA or BMA copolymer; even more preferably, MPC homopolymer, MPC and HEMA copolymer, MPC and BMA copolymer; particularly preferably MPC and BMA The copolymer of is illustrated. In the present specification, the MPC homopolymer or the copolymer of MPC and monomer (II) may be referred to as MPC polymer.

  The polymer used as the component (A) can be a commercially available product, and as the commercially available component (A), the Lipidure series (trade name: “LIPIDURE-PMB (BG ) "," LIPIDURE-PMB (Ph10) "," LIPIDURE-PMB "," LIPIDURE-HM "," LIPIDURE-HM-500 ").

  In the ophthalmic liquid composition-1 of the present invention, the content ratio of the component (A) is appropriately set according to the type of polymer to be the component (A), but as an example, an ophthalmic liquid The total amount of component (A) is 0.0001 to 5 w / v%, more preferably 0.0005 to 2 w / v%, still more preferably 0.001 to 1 w / v%, based on the total amount of Composition-1. Particularly preferred is 0.01 to 0.5 w / v%, and most preferred is 0.02 to 0.2 w / v%. The content ratio of the component (A) exemplified here is effective from the viewpoint of further improving the liquid drainage from the nozzle, and further suppresses the formation of precipitates, suppresses the adhesion of bacteria to SCL, and wettability of SCL. It is also suitable from the viewpoint of improving the cleaning effect of pollen protein adhering to ionic SHCL.

In addition to the component (A), the ophthalmic liquid composition-1 of the present invention comprises (B-1) at least one of chondroitin sulfate and its salt, and (B-2) hyaluronic acid and its salt. Or (B-3) glucose in a range that satisfies the following content ratios and ratios.
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
The content ratio of the component (B-3) is 0.005 to 0.2 w / v%, and the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more.
As described above, the component (A) and the component (B-1), the component (B-2), or the component (B-3) having a specific content ratio are contained in a specific ratio. It is possible to improve the poor liquid drainage from the nozzle and the liquid residue of the ophthalmic liquid composition on the outer surface of the nozzle after use, which are disadvantages when the composition contains the liquid. Furthermore, it is possible to improve the effect of suppressing the formation of precipitates, the suppression of bacterial adhesion to SCL, the improvement of wettability of SCL, or the pollen protein attached to ionic SHCL.

The component (B-1), that is, chondroitin sulfate and / or a salt thereof, is a polymer compound known as a kind of mucopolysaccharide that exhibits a moisturizing action in the ocular mucosa and the like. The chondroitin sulfate and salts thereof used in the present invention are not particularly limited in terms of their origin, and for example, those obtained from animals such as salmon and sharks, or those obtained from microorganisms It may be. Although it does not restrict | limit especially as a viscosity average molecular weight of the chondroitin sulfate used for this invention, For example, 10 million to 500,000, Preferably it is 50,000 to 200,000, More preferably, it is 10,000 to 100,000, Particularly preferably, those in the range of about 0.5 to 50,000, more particularly preferably about 7,000 to 40,000, and most preferably about 8,000 to 35,000 can be used. Here, the viscosity average molecular weight is determined according to the fifteenth revised Japanese Pharmacopoeia general test method Viscosity measurement method First method: Intrinsic viscosity η according to capillary viscometer method (measurement condition: solution 0.2 mol / L NaCl, temperature 25.0 ± 0 ° C., Ubbelohde viscometer) and the obtained intrinsic viscosity η is calculated from the following formula I.
Formula I: [η] = 5.8 × 10 ⁻⁴ M ^0.74 (where M is the viscosity average molecular weight)
Specific examples of the salt of chondroitin sulfate include salts with alkali metals such as sodium and potassium; salts with alkaline earth metals such as calcium and magnesium; salts with other metals such as aluminum and the like. The Preferred is an alkali metal salt of chondroitin sulfate, and more preferred is sodium chondroitin sulfate (hereinafter sometimes referred to as chondroitin sulfate Na).

  In the ophthalmic liquid composition-1 of the present invention, a commercially available chondroitin sulfate or a salt thereof can be used.

  In the ophthalmic liquid composition-1 of the present invention, the component (B-1) may be selected from chondroitin sulfate and salts thereof, and may be used alone. You may use combining a seed | species or more. The component (B-1) is preferably exemplified by sodium chondroitin sulfate.

  In the ophthalmic liquid composition-1 of the present invention, the content ratio of the component (B-1) is 0.05 to 0.5 w / component of the total amount of the component (B-1) with respect to the total amount of the ophthalmic liquid composition-1. V% may be satisfied, but preferably 0.1 to 0.5 w / v%, more preferably 0.2 to 0.5 w / v%.

  Further, in the ophthalmic liquid composition-1 of the present invention, regarding the ratio of the component (B-1) to the component (A), the total amount of the component (B-2) is 100 parts by weight of the total amount of the component (A). The content may be 5 parts by weight or more, preferably 5 to 5000 parts by weight, more preferably 25 to 1000 parts by weight.

  The content ratio of the component (B-1) exemplified here, and the ratio of the component (B-2) to the component (A) are effective from the viewpoint of further improving liquid drainage from the nozzle. It is also suitable from the viewpoints of suppressing the formation of precipitates, suppressing the adhesion of bacteria to SCL, improving the wettability of SCL, or improving the cleaning effect of pollen proteins attached to ionic SHCL.

  The component (B-2), that is, hyaluronic acid and / or a salt thereof, is a polymer compound known as a kind of mucopolysaccharide that exhibits a moisturizing action in the ocular mucosa and the like. The hyaluronic acid and salts thereof used in the present invention are not particularly limited in terms of their origin, and for example, they may be obtained from chicken crowns or derived from microorganisms. Although it does not restrict | limit especially as an average molecular weight of the hyaluronic acid used for this invention, For example, 10000-5 million, Preferably it is 10,000-4 million, More preferably, it is 10-2.5 million, Most preferably, it is 400,000- Examples are in the range of 2.5 million, more preferably in the range of 600,000 to 2,000,000.

Here, the average molecular weight of hyaluronic acid in this specification means the viscosity average molecular weight. The viscosity average molecular weight can be determined by a known measurement method. Specifically, hyaluronic acid and / or a salt thereof (dried product) is dissolved in a 0.2 M sodium chloride solution, the intrinsic viscosity (η) at 30 ° C. is obtained, and the Laurent equation (η (intrinsic viscosity) = 0. Based on 00003 × Mv (viscosity average molecular weight) ^0.78 ), the viscosity average molecular weight is calculated. The intrinsic viscosity (η) is measured according to the 15th revision Japanese Pharmacopoeia General Test Method Viscosity Measurement Method Method 1: Capillary Viscometer Method.

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

  In the ophthalmic liquid composition-1 of the present invention, commercially available hyaluronic acid and salts thereof can be used.

  In the ophthalmic liquid composition-1 of the present invention, the component (B-2) may be selected from hyaluronic acid and a salt thereof, and may be used alone. You may use combining a seed | species or more. The component (B-2) is preferably exemplified by sodium hyaluronate (hereinafter sometimes referred to as Na hyaluronate).

  In the ophthalmic liquid composition-1 of the present invention, the content ratio of the component (B-2) is 0.002 to 0.1 w / total component (B-2) with respect to the total amount of the ophthalmic liquid composition-1. V% may be satisfied, but preferably 0.015 to 0.1 w / v%, more preferably 0.02 to 0.1 w / v%.

  Further, in the ophthalmic liquid composition-1 of the present invention, regarding the ratio of the component (B-2) to the component (A), the total amount of the component (B-2) is 100 parts by weight of the total amount of the component (A). The content may be 0.1 parts by weight or more, preferably 0.1 to 3000 parts by weight, and more preferably 2 to 100 parts by weight.

  The content ratio of the component (B-2) exemplified here, and the ratio of the component (B-2) to the component (A) are effective from the viewpoint of further improving liquid drainage from the nozzle. It is also suitable from the viewpoints of suppressing the formation of precipitates, suppressing the adhesion of bacteria to SCL, improving the wettability of SCL, or improving the cleaning effect of pollen proteins attached to ionic SHCL.

  The component (B-3), that is, glucose is also a known compound. The origin of the glucose used in the ophthalmic liquid composition-1 of the present invention is not particularly limited.

  In the ophthalmic liquid composition-1 of the present invention, the content ratio of the component (B-3) is 0.005 to 0.2 w / component of the total amount of the component (B-3) with respect to the total amount of the ophthalmic liquid composition-1. Although it is sufficient to satisfy v%, it is preferably 0.02 to 0.2 w / v%, more preferably 0.05 to 0.2 w / v%.

  Further, in the ophthalmic liquid composition-1 of the present invention, regarding the ratio of the component (B-3) to the component (A), the total amount of the component (B-3) is 100 parts by weight of the total amount of the component (A). The content may be 1 part by weight or more, preferably 1 to 2000 parts by weight, more preferably 10 to 1000 parts by weight.

  The content ratio of the component (B-3) exemplified here, and the ratio of the component (B-3) to the component (A) are effective from the viewpoint of further improving liquid drainage from the nozzle. It is also suitable from the viewpoints of suppressing the formation of precipitates, suppressing the adhesion of bacteria to SCL, improving the wettability of SCL, or improving the cleaning effect of pollen proteins attached to ionic SHCL.

  Further, the ophthalmic liquid composition-1 of the present invention comprises ethylenediamineacetic acid, a derivative thereof, in addition to the component (A) and the component (B-1), the component (B-2) or the component (B-3). , And at least one selected from the group consisting of salts thereof (hereinafter sometimes simply referred to as (C-1) component) and / or sodium chloride (hereinafter simply referred to as (C-2) component) It may be preferable to contain). As described above, by including the component (C-1) and / or the component (C-2), the ophthalmic liquid composition-1 of the present invention makes the liquid breakage from the nozzle remarkably good, and after use. It is possible to more effectively suppress the liquid residue on the outer surface of the nozzle.

  The ethylenediamineacetic acid used as the component (C-1) is a compound in which 1 to 4 carboxymethyl groups are bonded to the two amino groups of ethylenediamine, and is used as the component (C-1) in the present invention. The ethylenediamineacetic acid to be used is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specific examples of ethylenediamineacetic acid used in the present invention include ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (edetic acid, EDTA), and the like. Examples of the ethylenediamineacetic acid derivative include N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA) and diethylenetriaminepentaacetic acid (DTPA). Among these ethylenediamineacetic acids and derivatives thereof, ethylenediaminetetraacetic acid is preferable. These ethylenediamineacetic acids and / or their derivatives may be used alone or in any combination of two or more.

  The salt of ethylenediamineacetic acid and / or its derivative used as component (C-1) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specifically, organic acid salts [for example, monocarboxylate (acetate, trifluoroacetate, butyrate, palmitate, stearate, etc.), polyvalent carboxylate (fumarate, maleate) Acid salt, succinate, malonate, etc.), oxycarboxylate (lactate, tartrate, citrate, etc.), organic sulfonate (methanesulfonate, toluenesulfonate, tosylate, etc.) Etc.], inorganic acid salts (eg, hydrochloride, sulfate, nitrate, hydrobromide, phosphate, etc.), salts with organic bases (eg, methylamine, triethylamine, triethanolamine, morpholine, piperazine) Salts with organic amines such as pyrrolidine, tripyridine, picoline), salts with inorganic bases [eg ammonium salts; alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), metals such as aluminum Etc.] and the like. Among these salts, preferred are salts with inorganic bases, more preferred are alkali metal salts, still more preferred are sodium salts and potassium salts, and particularly preferred are sodium salts. These salts may be used alone or in any combination of two or more.

  The ethylenediamineacetic acid, its derivative and / or salt thereof used as the component (C-1) may be in the form of a hydrate.

  When the component (C-1) is added to the ophthalmic liquid composition-1 of the present invention, ethylenediamineacetic acid, its derivatives, and salts thereof may be selected and used alone. In addition, two or more kinds may be used in any combination. The component (C-1) used in the present invention is preferably ethylenediaminetetraacetic acid and / or a salt thereof, more preferably ethylenediaminetetraacetic acid and / or a sodium salt thereof, still more preferably disodium ethylenediaminetetraacetic acid and / or a salt thereof. And ethylenediaminetetraacetic acid disodium dihydrate.

  When blending the component (C-1) in the ophthalmic liquid composition-1 of the present invention, the content ratio of the component (C-1) is appropriately set according to the type of the component (C-1) However, for example, the total amount of the component (C-1) is 0.0005 to 0.2 w / v%, preferably 0.001 to 0.1 w / v% with respect to the total amount of the ophthalmic liquid composition-1. More preferably, 0.005 to 0.05 w / v% is exemplified.

  In the ophthalmic liquid composition-1 of the present invention, the ratio of the component (C-1) to the component (A) is not particularly limited as long as the content ratio described above is satisfied, but the total amount of the component (A) Ratio in which the total amount of component (C-1) per 100 parts by weight is 0.1 to 1000 parts by weight, preferably 1 to 500 parts by weight, more preferably 3 to 200 parts by weight, and particularly preferably 5 to 100 parts by weight. It is desirable to satisfy

  When the component (C-1) satisfies the above-described content ratio and ratio, the effects of the present invention including the improvement of liquid loss of the ophthalmic liquid composition from the nozzle can be more effectively exhibited. ,preferable.

  When the component (C-2) is blended with the ophthalmic liquid composition-1 of the present invention, the content ratio of the component (C-2) varies depending on the type of the component (C-2) used, Although it cannot be defined uniformly, for example, the total amount of the component (C-2) is 0.01 to 10 w / v%, preferably 0.05 to 5 w / w with respect to the total amount of the ophthalmic liquid composition-1. Examples are v%, more preferably 0.1 to 2 w / v%.

  In the ophthalmic liquid composition-1 of the present invention, the ratio of the component (C-2) to the component (A) is not particularly limited as long as the content ratio described above is satisfied, but the total amount of the component (A) Satisfies a ratio that the total amount of component (C-2) is 1 to 10000 parts by weight, preferably 5 to 7000 parts by weight, more preferably 10 to 5000 parts by weight, and particularly preferably 50 to 1000 parts by weight per 100 parts by weight. It is desirable to do.

  When the component (C-2) satisfies the above-described content and ratio, the effect of the present invention can be exhibited more effectively, which is preferable.

  The ophthalmic liquid composition-1 of the present invention may contain an isotonic agent other than the component (C-2). The isotonic agent (other than sodium chloride) that can be blended in the ophthalmic liquid composition-1 of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Not. Specific examples of such isotonic agents include, for example, sodium bisulfite, sodium sulfite, potassium chloride, calcium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerin, Examples include propylene glycol. These isotonic agents may be used alone or in any combination of two or more.

  When an isotonic agent (other than sodium chloride) is blended in the ophthalmic liquid composition-1 of the present invention, the content of the tonicity agent is appropriately set according to the type of tonicity agent used, etc. For example, the total amount of the tonicity agent (other than sodium chloride) is 0.01 to 10 w / v%, preferably 0.05 to 5 w / v with respect to the total amount of the ophthalmic liquid composition-1. %, More preferably 0.1 to 2 w / v%.

It is desirable that the ophthalmic liquid composition-1 of the present invention further contains a buffer. The buffer that can be incorporated into the ophthalmic liquid composition-1 of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Examples of such buffers include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, tris buffer, epsilon-aminocaproic acid, aspartic acid, aspartate and the like. These buffering agents may be used in combination. Preferred buffering agents are borate buffer, phosphate buffer, carbonate buffer, and citrate buffer, and particularly preferred buffers are borate buffer and phosphate buffer. Examples of the boric acid buffer include borates such as alkali metal borate and alkaline earth metal borate. Examples of the phosphate buffer include phosphates such as alkali metal phosphates and alkaline earth metal phosphates. Examples of the carbonate buffer include carbonates such as alkali metal carbonates and alkaline earth metal carbonates. Examples of the citrate buffer include alkali metal citrate and alkaline earth metal citrate. Moreover, you may use the borate or the hydrate of a phosphate as a borate buffer or a phosphate buffer. As more specific examples, boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.), phosphoric acid or a salt thereof (disodium hydrogen phosphate, dihydrogen phosphate) Sodium, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate), carbonic acid or a salt thereof (sodium hydrogen carbonate, sodium carbonate, ammonium carbonate, potassium carbonate, Calcium carbonate, potassium hydrogen carbonate, magnesium carbonate, etc.), citric acid or a salt thereof (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.), acetic acid or a salt thereof (ammonium acetate) , Potassium acetate, calcium acetate, sodium acetate, etc.), asparagus Examples thereof include formic acid or a salt thereof (sodium aspartate, magnesium aspartate, potassium aspartate, etc.). Among these buffers, phosphate buffer and borate buffer are preferable. In particular, the borate buffer is preferable from the point of further enhancing the effect of the present invention. Among them, the point of further effectively suppressing the liquid residue on the external surface of the nozzle after use, the point of increasing the effect of suppressing bacterial adhesion in SCL, SHCL This is particularly effective in that the pollen protein washing effect and the like are more effectively exhibited. These buffering agents may be used alone or in any combination of two or more. Among boric acid buffers, particularly preferred are boric acid and / or borax, and most preferred is an embodiment in which boric acid and borax are used in combination.

  When a buffering agent is blended in the ophthalmic liquid composition-1 of the present invention, the content of the buffering agent varies depending on the type of buffering agent used, the type and amount of other blending components, and is uniformly specified. For example, the total amount of the buffer is 0.01 to 10 w / v%, preferably 0.1 to 5 w / v%, more preferably 0 with respect to the total amount of the ophthalmic liquid composition-1 The ratio which becomes 0.5-2 w / v% is illustrated. When the buffer is a borate buffer, the total amount of borate buffer is 0.1 to 5 w / v%, preferably 0.1 to 3 w /% with respect to the total amount of the ophthalmic liquid composition-1. Examples are v%, more preferably 0.2 to 2 w / v%, particularly preferably 0.5 to 2 w / v%.

  The ophthalmic liquid composition-1 of the present invention preferably further contains a surfactant. The surfactant that can be incorporated into the ophthalmic liquid composition-1 of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable, and is nonionic. Any of a surfactant, an amphoteric surfactant, an anionic surfactant, and a cationic surfactant may be used.

  Specific examples of the nonionic surfactant that can be blended in the ophthalmic liquid composition-1 of the present invention include monolauric acid POE (20) sorbitan (polysorbate 20), monopalmitic acid POE (20) sorbitan (polysorbate). 40), POE sorbitan fatty acid esters such as monostearic acid POE (20) sorbitan (polysorbate 60), tristearic acid POE (20) sorbitan (polysorbate 65), monooleic acid POE (20) sorbitan (polysorbate 80); POE / POP block copolymers such as Poloxamer 407, Poloxamer 235, Poloxamer 188, Poloxamer 403, Poloxamer 237, Poloxamer 124; POE cured castor oils such as POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60); POE alkyl ethers such as POE (9) lauryl ether; POE-POP alkyl ethers such as POE (20) POP (4) cetyl ether S; POE (10) POE alkylphenyl ethers such as nonylphenyl ether. In the compounds exemplified above, POE is polyoxyethylene, POP is polyoxypropylene, and the numbers in parentheses indicate the number of moles added. Specific examples of the amphoteric surfactant that can be incorporated into the ophthalmic liquid composition-1 of the present invention include alkyldiaminoethylglycine. Specific examples of the cationic surfactant that can be blended in the ophthalmic liquid composition-1 of the present invention include benzalkonium chloride and benzethonium chloride. Specific examples of the anionic surfactant that can be added to the ophthalmic liquid composition-1 of the present invention include alkylbenzene sulfonate, alkyl sulfate, polyoxyethylene alkyl sulfate, and aliphatic α-. Examples include sulfomethyl ester and α-olefin sulfonic acid. In the ophthalmic liquid composition-1 of the present invention, these surfactants may be used alone or in combination of two or more. Preferred surfactants are nonionic surfactants, more preferably POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60), poloxamer 407, monooleic acid POE (20) sorbitan (polysorbate) 80).

  When a surfactant is blended in the ophthalmic liquid composition-1 of the present invention, the content of the surfactant can be appropriately set according to the type of surfactant, the type and amount of other blended components, and the like. As an example of the content ratio of the surfactant, the total amount of the surfactant is 0.001 to 1.0 w / v%, preferably 0.005 to 0.5 w, with respect to the total amount of the ophthalmic liquid composition-1. / v%, more preferably 0.01 to 0.3 w / v%.

  The pH of the ophthalmic liquid composition-1 of the present invention is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable range. An example of the pH of the ophthalmic liquid composition-1 of the present invention includes a range of 4.0 to 9.5, preferably 5.0 to 8.5, and more preferably 5.4 to 8.0. .

  Further, the osmotic pressure of the ophthalmic liquid composition-1 of the present invention is not particularly limited as long as it is within a range acceptable for a living body. As an example of the osmotic pressure ratio of the ophthalmic liquid composition-1 of the present invention, it is preferably 0.7 to 5.0, more preferably 0.9 to 3.0, and particularly preferably 1.0 to 2.0. A range is mentioned. The osmotic pressure can be adjusted by a method known in the art using inorganic salts, polyhydric alcohols, sugar alcohols, saccharides and the like. The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to the osmotic pressure of 0.9 w / v% sodium chloride aqueous solution based on the 15th revised Japanese Pharmacopoeia. Measure with reference to. The standard solution for measuring the osmotic pressure ratio was sodium chloride (Japanese Pharmacopoeia standard reagent) dried at 500-650 ° C for 40-50 minutes, and then allowed to cool in a desiccator (silica gel). Dissolve in water to prepare exactly 100 mL, or use a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution).

  In addition to the above components, an active ingredient (pharmacologically active ingredient, physiologically active ingredient, etc.) can be added to the ophthalmic liquid composition-1 of the present invention. The type of such component is not particularly limited, and examples thereof include a decongestant component, an eye muscle modulator component, an anti-inflammatory component or an astringent component, an antihistamine component or an antiallergic component, vitamins, amino acids, antibacterial agents. Examples thereof include a drug component or a bactericidal component, a saccharide, a polymer compound or derivative thereof, cellulose or a derivative thereof, a local anesthetic component, a glaucoma treatment component, a cataract treatment component, and the like. Examples of the pharmacologically active component and physiologically active component suitable in the present invention include the following components.

  Decongestant: For example, α-adrenergic agonists, specifically epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, oxymetazoline hydrochloride, tetrahydrozoline hydrochloride, naphazoline hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride, epinephrine hydrogen tartrate, naphazoline nitrate. These may be d-form, l-form or dl-form.

  Ocular muscle modulator component: For example, cholinesterase inhibitor having an active center similar to acetylcholine, specifically, neostigmine methyl sulfate, tropicamide, helenien, atropine sulfate and the like.

  Anti-inflammatory component or astringent component: for example, zinc sulfate, zinc lactate, allantoin, epsilon-aminocaproic acid, indomethacin, lysozyme chloride, silver nitrate, pranoprofen, sodium azulenesulfonate, dipotassium glycyrrhizinate, diammonium glycyrrhizinate, Diclofenac sodium, bromfenac sodium, berberine chloride, berberine sulfate, etc.

  Antihistamine component or antiallergic agent component: for example, agitazanolast, diphenhydramine or its hydrochloride, chlorpheniramine maleate, ketotifen fumarate, levocabastine or its hydrochloride, etc., amlexanox, ibudilast, tazanolast, tranilast, oxatomide, Suplatast or its tosylate, such as sodium cromoglycate, potassium pemirolast, etc.

  Vitamins: for example, retinol acetate, retinol palmitate, pyridoxine hydrochloride, flavin adenine dinucleotide sodium, pyridoxal phosphate, cyanocobalamin, panthenol, calcium pantothenate, sodium pantothenate, ascorbic acid, tocopherol acetate, tocopherol nicotinate, succinic acid Tocopherol, tocopherol calcium succinate, ubiquinone derivatives, etc.

  Amino acids: for example, aminoethylsulfonic acid (taurine), glutamic acid, creatinine, sodium aspartate, potassium aspartate, magnesium aspartate, magnesium aspartate / potassium mixture, glutamic acid, sodium glutamate, magnesium glutamate, epsilon-aminocaproic acid, glycine , Alanine, arginine, lysine, γ-aminobutyric acid, γ-aminovaleric acid and the like. These may be d-form, l-form or dl-form.

  Antibacterial component or bactericidal component: for example, alkylpolyaminoethylglycine, chloramphenicol, sulfamethoxazole, sulfisoxazole, sulfamethoxazole sodium, sulfisoxazole diethanolamine, sulfisoxa Zole monoethanolamine, sodium sulfisomezole, sodium sulfisomidine, ofloxacin, norfloxacin, levofloxacin, lomefloxacin hydrochloride, acyclovir and the like.

  Sugars: For example, monosaccharides, disaccharides, specifically maltose, trehalose, sucrose, cyclodextrin, xylitol, sorbitol, mannitol and the like.

  Macromolecular compound or derivative thereof: for example, alginic acid, sodium alginate, dextrin, dextran, pectin, polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, polyacrylic acid, carboxyvinyl polymer, macrogol and pharmaceutically acceptable thereof Such as salt.

  Cellulose or derivatives thereof: for example, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose sodium, carboxyethyl cellulose, nitrocellulose and the like.

  Local anesthetic components: for example, chlorobutanol, procaine hydrochloride, lidocaine hydrochloride, etc.

  The content ratios of various components are known in the field of ophthalmic liquid compositions, and the content ratios of the above components in the ophthalmic liquid composition-1 of the present invention are determined according to the dosage form and pharmacology of the ophthalmic liquid composition-1. It is appropriately set according to the type of active ingredient or bioactive ingredient. For example, the content ratio of the pharmacologically active ingredient or the physiologically active ingredient can be selected from the range of about 0.0001 to 30 w / v%, preferably about 0.001 to 10 w / v% with respect to the total amount of the ophthalmic liquid composition-1.

  In addition, in the ophthalmic liquid composition-1 of the present invention, various components and additives are appropriately selected according to conventional methods according to the use and form as long as the effects of the invention are not impaired. Or more than that can be used in combination. As those components or additives, for example, carriers (aqueous solvents, aqueous or oily bases, etc.) commonly used in the preparation of semi-solids and liquids, fragrances or refreshing agents, preservatives, fungicides or Various additives, such as an antibacterial agent, a pH adjuster, a chelating agent, and a stabilizer, can be mentioned. Although the typical component used for the ophthalmic liquid composition of this invention is illustrated below, it is not limited to these.

  Carrier: An aqueous solvent such as water or hydrous ethanol.

  Perfume or refreshing agent: For example, terpenes (specifically, anethole, eugenol, camphor, geraniol, cineol, borneol, menthol, limonene, ryuuno, etc. These may be any of d-form, l-form or dl-form. ), Essential oils (such as fennel oil, cool mint oil, cinnamon oil, spearmint oil, mint water, mint oil, peppermint oil, bergamot oil, eucalyptus oil, rose oil).

  Preservatives, bactericides or antibacterials: for example, polydronium chloride, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, dehydroacetic acid Sodium, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide or its hydrochloride) , Glow Kill (trade name, manufactured by Rhodia).

  pH adjuster: For example, hydrochloric acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, monoethanolamine, diisopropanolamine, sulfuric acid, phosphoric acid and the like.

  Chelating agent: for example, ascorbic acid, citric acid and the like.

  Stabilizers: dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate, etc.

  The ophthalmic liquid composition-1 of the present invention contains 90 w / v% or more of water, preferably 94 w / v% or more, more preferably 96 w / v% or more, particularly preferably 97 to 99.5 w / v%. . The water used in the ophthalmic liquid composition-1 of the present invention may be water that is pharmaceutically, pharmacologically (pharmaceutically) 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 15th revision Japanese Pharmacopoeia.

  The ophthalmic liquid composition-1 of the present invention comprises a desired amount of the above component (A), the component (B-1), the component (B-2) or the component (B-3), and other components as necessary. It is prepared by adding the compounding ingredients to a desired concentration.

  In addition, the ophthalmic liquid composition-1 of the present invention includes eye drops (however, eye drops include eye drops that can be instilled while wearing contact lenses (eye drops for contact lenses)), contact lens mounting liquids, eyewashes. Agents (however, eyewashes include eyewashes that can be washed while wearing contact lenses (contact lens eyewashes)), contact lens care agents (contact lens disinfectants, contact lens preservatives, contact lens washers) Agents, contact lens cleaning preservatives, etc.). Among these, eye drops, eye washes, and contact lens mounting liquids are suitable pharmaceutical forms for the ophthalmic liquid composition-1 of the present invention because they are required to maintain high quality as pharmaceuticals or pharmaceuticals. In addition, eye drops and contact lens mounting liquids are used in a form that requires only a small amount of liquid to be used at a time and is used by extruding one drop at a time. This is a preferred preparation form of the ophthalmic liquid composition-1 of the invention. In particular, it is practically very difficult for eye drops to be instilled at a fixed angle at all times. Since it is essential, it is a particularly suitable formulation form. In the present specification, the term “contact lens” includes all contact lenses including hard contact lenses, soft contact lenses, and silicone hydrogel lenses.

  In addition, eye drops, eye washes, and SCL mounting solutions tend to adhere to the edge of the eye and eyelashes during use, but as shown in Test Example 2 described later, It has been clarified that the component 1), the component (B-2) or the component (B-3) tends to generate precipitates when attached to the edge of the eye or eyelashes. The formation of such precipitates may impair the user's cosmetic appearance. In contrast, according to the ophthalmic liquid composition-1 of the present invention, the component (A) and the component (B-1), the component (B-2), or the component (B-3) are used in combination. Thus, it is possible to suppress the formation of precipitates even when adhering to the edge of the eye or the eyelashes. When emphasizing the effective expression of such properties, eye drops, eye washes, and SCL mounting solutions are exemplified as examples of suitable formulation forms of the ophthalmic liquid composition-1 of the present invention. In the case of SCL eye drops and SCL eye wash, it may be applied directly to the eye wearing SCL, or may be applied to the eye before wearing SCL.

  In addition, as shown in Test Example 3 to be described later, the adhesion of bacteria to SCL by using (A) component together with (B-1) component, (B-2) component or (B-3) component Can be remarkably suppressed. Furthermore, as shown in Test Example 4 to be described later, the wettability of SCL is improved by using (A) component together with (B-1) component, (B-2) component or (B-3) component. Can improve the wearing feeling of SCL. When emphasizing the effective expression of such characteristics, as an example of a suitable formulation form of the ophthalmic liquid composition-1 of the present invention, an eye drop that can be applied while wearing SCL (an eye drop for SCL), SCL wearing solution, eyewash that can be washed while wearing SCL (eyewash for SCL), SCL care agent; preferably SCL eye drop, SCL wearing solution, SCL eye wash; more preferably SCL eye drop Is exemplified.

  Furthermore, as shown in Reference Example 1 to be described later, it has been clarified that ionic SHCL among the SCLs remarkably easily adsorbs pollen proteins. Such adsorption of pollen protein not only shortens the period of use of ionic SHCL, but may also contribute to allergic symptoms. On the other hand, according to the ophthalmic liquid composition-1 of the present invention, by using the components (A) and (B) in combination, the cleaning effect of pollen protein adhering to ionic SHCL can be significantly improved. Can do. When emphasizing the effective expression of such characteristics, as an example of a suitable formulation form of the ophthalmic liquid composition-1 of the present invention, an eye drop that can be instilled while wearing ionic SHCL (SHCL eye drop), Eyewash that can be washed while wearing ionic SHCL (eyewash for ionic SCL), contact lens mounting solution for ionic SHCL, ionic SHCL care agent; preferably, eye drops for ionic SHCL, ionic SHCL Eyewashes for ionic SHCL, ionic SHCL care agents; more preferably, ionic SHCL eyewash agents and ionic SHCL care agents. In addition, ionicity here means that the ionic component content rate in a contact lens raw material is 1 mol% or more according to the US FDA (US Food and Drug Administration) standard so that those skilled in the art usually understand.

  The ophthalmic liquid composition-1 of the present invention is effective for preventing or treating dry eye and dry eyes based on the component (A), and is also useful as an agent for improving dry eye and dry eyes.

  The ophthalmic liquid composition-1 of the present invention is used by being housed in a container generally used in the ophthalmic field, that is, a container having a nozzle. More specifically, when the ophthalmic liquid composition-1 of the present invention is an eye drop, it is used by being housed in an eye drop container. In addition, as an eye drop container for containing the ophthalmic liquid composition-1 of the present invention, a container having a nozzle attached to the container, and a nozzle part (liquid pouring part) and a container main body are integrally molded. Any one having a structure (for example, a single-use type eye drop) may be used.

  The container for storing the ophthalmic liquid composition-1 of the present invention may be made of glass or plastic. When the plastic container is used as the container for storing the ophthalmic liquid composition-1 of the present invention, the constituent material of the plastic container is not particularly limited. For example, polyethylene naphthalate, polyarylate, polyethylene terephthalate, polypropylene , Any one of polyethylene and polyimide, a copolymer thereof, or a mixture of two or more thereof. In addition, as the copolymer, ethylene-2,6-naphthalate unit, arylate unit, ethylene terephthalate unit, propylene unit, ethylene unit, imide unit is mainly used, and other polyester units and imide units are included. Examples of the copolymer include.

  Further, the structure and constituent materials of the nozzle provided in the container for storing the ophthalmic liquid composition-1 of the present invention are not particularly limited. The structure of the nozzle may be a structure generally employed in eye drop containers, eye wash containers, etc., and the constituent material of the nozzle is exemplified by the same material as that of the plastic container, for example. Is done. From the viewpoint of making the ophthalmic liquid composition-1 of the present invention to be more easily drained, the container containing the ophthalmic liquid composition-1 of the present invention includes a nozzle containing polyethylene or polypropylene as a constituent material. A mounted container is preferable, and a container mounted with a nozzle containing polyethylene as a constituent material is particularly preferable. Examples of the type of polyethylene include high-density polyethylene and low-density polyethylene. Among them, a nozzle including low-density polyethylene as a constituent material is preferable.

2. Ophthalmic liquid composition-2
The ophthalmic liquid composition-2 of the present invention is an ophthalmic liquid composition used for SCL.

  The ophthalmic liquid composition-2 of the present invention is a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another copolymerizable monomer (hereinafter simply referred to as “component (A)”). May be included). The kind of the component (A) used in the ophthalmic liquid composition-2 of the present invention, a suitable example of the component (A), and the content ratio of the component (A) are as described above for the ophthalmic liquid composition-1. It is the same as the component (A) used in 1.

  In addition to the component (A), the ophthalmic liquid composition-2 of the present invention includes at least one of (B) chondroitin sulfate, hyaluronic acid, salts thereof, and glucose (hereinafter simply referred to as the component (B)). In some cases). Thus, it becomes possible to suppress effectively the adhesion | attachment of the microbe to SCL by using together (A) and (B) component. In addition, the combined use of the component (A) and the component (B) is also effective in improving the effect of enhancing the wettability of SCL and the effect of cleaning pollen proteins attached to ionic SHCL.

  In the ophthalmic liquid composition-2 of the present invention, the chondroitin sulfate, chondroitin sulfate salt, hyaluronic acid, hyaluronic acid salt, and glucose used as component (B) are the same as in the above ophthalmic liquid composition-1. It is the same as that used for the component (B-1), the component (B-2) and the component (B-3) used.

  In the ophthalmic liquid composition-2 of the present invention, the component (B) is selected from chondroitin sulfate, chondroitin sulfate salt, hyaluronic acid, hyaluronic acid salt, glucose, and used alone. Alternatively, two or more of these may be used in combination.

  Among the components (B), from the viewpoint of more effectively suppressing the adhesion of bacteria to SCL, preferably an alkali metal salt of chondroitin sulfate, an alkali metal salt of hyaluronic acid, glucose; more preferably sodium chondroitin sulfate, hyaluronic acid Examples are sodium and glucose. These components (B) are also suitable from the viewpoint of further improving the cleaning effect of pollen proteins attached to ionic SHCL.

In the ophthalmic liquid composition-2 of the present invention, the content ratio of the component (B) is appropriately set according to the type of the component (B), the type of the component (A) to be used in combination, etc. The total amount of the component (B) is 0.0002 to 1.5 w / v%, preferably 0.001 to 0.5 w / v%, based on the total amount of the liquid composition-2 for use. More specifically, the following ranges are exemplified as the content ratio of the component (B).
When component (B) is chondroitin sulfate and / or a salt thereof: these are total amounts, usually 0.005 to 1 w / v%, preferably 0.01 to 0.5, more preferably 0.05 to 0.5 w. / v%,
When component (B) is hyaluronic acid and / or a salt thereof: these are total amounts, usually 0.0002 to 0.1 w / v%, preferably 0.001 to 0.1 w / v%, more preferably 0. 002 to 0.1 w / v%, particularly preferably 0.01 to 0.1 w / v%
When component (B) is glucose: Usually 0.001 to 0.5 w / v%, preferably 0.002 to 0.3 w / v%, more preferably 0.005 to 0.2 w / v%, particularly preferably 0.005-0.2w / v%
The content ratio of the component (B) exemplified here is effective from the viewpoint of more effectively suppressing the adhesion of the bacteria to the SCL, and further, the improvement of the wettability of the SCL or the pollen adhered to the ionic SHCL. It is also suitable from the viewpoint of improving the protein washing effect.

In the ophthalmic liquid composition-2 of the present invention, the ratio of the component (B) to the component (A) is not particularly limited as long as the content ratio described above is satisfied, but the total amount of the component (A) is 100% by weight. It is desirable to satisfy such a ratio that the total amount of component (B) is 0.1 to 50000 parts by weight, preferably 0.5 to 1000 parts by weight, and more preferably 1 to 500 parts by weight. More specifically, the following ranges are exemplified as the ratio of the component (B) to 100 parts by weight of the total amount of the component (A).
When component (B) is chondroitin sulfate and / or a salt thereof: These are total amounts, usually 5 to 50000 parts by weight, preferably 5 to 5000 parts by weight, more preferably 10 to 500 parts by weight.
When component (B) is hyaluronic acid and / or a salt thereof: the total amount is usually 0.1 to 30000 parts by weight, preferably 1 to 3000 parts by weight, more preferably 2 to 300 parts by weight, particularly preferably 2 ~ 100 parts by weight
When component (B) is glucose: usually 0.1 to 20000 parts by weight, preferably 1 to 2000 parts by weight, more preferably 1 to 1000 parts by weight, and particularly preferably 1 to 500 parts by weight. (A) The ratio of the component (B) to the component is effective from the viewpoint of more effectively suppressing the adhesion of the bacteria to the SCL, and further, improving the wettability of the SCL or washing the pollen protein attached to the ionic SHCL. It is also suitable from the viewpoint of improving the effect.

  The component (B) may be used alone or in combination. Preferred combinations include chondroitin sulfate or a salt thereof and hyaluronic acid or a salt thereof, chondroitin sulfate or a salt thereof and glucose, hyaluronic acid or a salt thereof and glucose, chondroitin sulfate or a salt thereof, hyaluronic acid or a salt thereof and glucose, and the like. . Particularly preferred combinations include sodium chondroitin sulfate and sodium hyaluronate, sodium chondroitin sulfate and glucose, sodium hyaluronate and glucose, sodium chondroitin sulfate, sodium hyaluronate and glucose, and the like.

  Furthermore, the ophthalmic liquid composition-2 of the present invention is at least one selected from the group consisting of ethylenediamineacetic acid, derivatives thereof, and salts thereof in addition to the above components (A) and (B) (hereinafter referred to as “component (A)”). And / or sodium chloride (hereinafter sometimes simply referred to as component (C-2)). Types of (C-1) component and (C-2) component used in ophthalmic liquid composition-2 of the present invention, preferred examples of (C-1) component and (C-2) component, The content ratio of the component (C-1) and the component (C-2) is the same as the component (C-1) and component (C-2) used in the ophthalmic liquid composition-1. is there.

  The ophthalmic liquid composition-2 of the present invention may further contain an isotonic agent other than sodium chloride. About the kind of tonicity agent (other than sodium chloride) used in the ophthalmic liquid composition-2 of the present invention and the content ratio of the isotonic agent, isotonicity used in the above ophthalmic liquid composition-1 The same as in the case of the agent (other than sodium chloride).

  In addition to the components (A) and (B), the ophthalmic liquid composition-2 of the present invention preferably further contains a buffer. About the kind of buffer used in the ophthalmic liquid composition-2 of the present invention, a suitable example of the buffer, and the content of the buffer, the buffer used in the ophthalmic liquid composition-1 It is the same as the case of.

  The ophthalmic liquid composition-2 of the present invention preferably further contains a surfactant. The type of surfactant used in the ophthalmic liquid composition-2 of the present invention, a suitable example of the surfactant, and the content ratio of the surfactant are used in the ophthalmic liquid composition-1. This is the same as the case of the surfactant.

  The pH and osmotic pressure of the ophthalmic liquid composition-2 of the present invention are the same as those of the ophthalmic liquid composition-1.

  In addition to the above components, the ophthalmic liquid composition-2 of the present invention can contain active ingredients (pharmacologically active ingredients, physiologically active ingredients, etc.), various other ingredients, additives, and the like. Also in these cases, the type, content ratio, and the like are the same as in the case of the ophthalmic liquid composition-1.

  The ophthalmic liquid composition-2 of the present invention is prepared by adding a desired amount of the above-described component (A), component (B), and other components as necessary to a desired concentration. .

  The ophthalmic liquid composition-2 of the present invention is used as an ophthalmic liquid composition for SCL, and specific examples of the formulation include eye drops that can be instilled while wearing SCL (eye drops for SCL), SCL Eyewash that can be washed while wearing (eyewash for SCL), SCL mounting solution, SCL care agent (including SCL disinfectant, SCL preservative, SCL cleaner, SCL cleaner, etc.) Illustrated. In the case of SCL eye drops and SCL eye wash, it may be applied directly to the eye wearing SCL, or may be applied to the eye before wearing SCL.

  Among these, the eye drops for SCL, the eye wash for SCL, the detergent for SCL, and the SCL mounting liquid are preferable, and the eye drops for SCL are particularly suitable for the ophthalmic liquid composition-2 of the present invention.

  Furthermore, as shown in Reference Example 1 described later, among SCLs, ionic SHCL remarkably easily adsorbs pollen protein, and the ophthalmic liquid composition for ionic SHCL has a high cleaning effect on adsorbed pollen protein. However, according to the ophthalmic liquid composition-2 of the present invention, it is possible to remarkably improve the cleaning effect of pollen proteins adhering to ionic SHCL. In view of such characteristics, as an example of a suitable formulation form of the ophthalmic liquid composition-2 of the present invention, preferably an ophthalmic liquid composition for ionic SHCL, more preferably an ophthalmic solution for ionic SHCL, an ionic SHCL. Eye wash, ionic SHCL detergent, ionic SHCL mounting solution, particularly preferably ionic SHCL eye drops.

  The ophthalmic liquid composition-2 of the present invention is effective for preventing or treating dry eye and dry eyes based on the component (A), and is also useful as an agent for improving dry eye and dry eyes. In addition, the ophthalmic liquid composition-2 of the present invention is excellent in the effect of washing away pollen proteins adhering to ionic SHCL, so that ionic SHCL can be kept clean, and further, allergic symptoms can be observed for hay fever patients. Since the risk of onset can be reduced, it is also useful as an agent for improving allergic symptoms caused by pollen and the like and an eye itch.

  The container for storing the ophthalmic liquid composition-2 of the present invention is the same as in the case of the ophthalmic liquid composition-1.

3. Method for improving liquid drainage from nozzle, method for improving liquid remaining on nozzle As described above, liquid ophthalmic liquid composition containing component (A) has poor liquid drainage from nozzle, or liquid remaining on nozzle after use Can be improved by using the component (B-1), the component (B-2) or the component (B-3) with a specific content ratio.

Accordingly, the present invention also provides methods of the following embodiments I-1 to I-4 from another viewpoint.
I-1. In the ophthalmic liquid composition, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B-1) chondroitin sulfate and a salt thereof At least one, (B-2) at least one of hyaluronic acid and its salt, or (B-3) glucose.
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
(B-3) The content ratio of the component is 0.005 to 0.2 w / v%, and it is used in combination so that the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more. A method for improving the drainage of an ophthalmic liquid composition from a nozzle.
I-2. (A) To an ophthalmic liquid composition containing a polymer obtained by polymerizing a monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, (B-1) in chondroitin sulfate and salts thereof At least one, (B-2) at least one of hyaluronic acid and its salt, or (B-3) glucose.
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
(B-3) The content ratio of the component is 0.005 to 0.2 w / v%, and the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more. A method for improving the drainage of an ophthalmic liquid composition from a nozzle.
I-3. In the ophthalmic liquid composition, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B-1) chondroitin sulfate and a salt thereof At least one, (B-2) at least one of hyaluronic acid and its salt, or (B-3) glucose.
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
(B-3) The content ratio of the component is 0.005 to 0.2 w / v%, and it is used in combination so that the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more. A method for improving the liquid residue of an ophthalmic liquid composition on a nozzle.
I-4. (A) To an ophthalmic liquid composition containing a polymer obtained by polymerizing a monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, (B-1) in chondroitin sulfate and salts thereof At least one, (B-2) at least one of hyaluronic acid and its salt, or (B-3) glucose.
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
(B-3) The content ratio of the component is 0.005 to 0.2 w / v%, and the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more. A method for improving the liquid residue of an ophthalmic liquid composition on a nozzle.

  In these methods, the type (A), the component (B-1), the type (B-2) or the component (B-3) used, the content ratio and ratio thereof, the types of other components to be blended, The content ratio, the formulation form of the ophthalmic liquid composition, the type of the container for storing the ophthalmic liquid composition, and the like are the same as those described in “1. Ophthalmic liquid composition-1”.

4). As described above , the generation of precipitates of the ophthalmic liquid composition containing the (B-1) component, the (B-2) component, or the (B-3) component having a specific content ratio, as described above, (A) It can suppress by using a component. Therefore, the present invention also provides methods of the following embodiments II-1 and II-2 from still another viewpoint.
II-1. In the ophthalmic liquid composition, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B-1) chondroitin sulfate and a salt thereof At least one, (B-2) at least one of hyaluronic acid and its salt, or (B-3) glucose.
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
(B-3) The content ratio of the component is 0.005 to 0.2 w / v%, and it is used in combination so that the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more. A method for suppressing the formation of precipitates of an ophthalmic liquid composition comprising the component (B-1), the component (B-2), or the component (B-3), which is characterized.
II-2. (B-1) 0.05 to 0.5 w / v% of at least one of chondroitin sulfate and its salt, (B-2) 0.002 to 0.1 w / v% of at least one of hyaluronic acid and its salt, Or (B-3) another monomer capable of homogenizing or copolymerizing the monomer represented by the general formula (I) in an ophthalmic liquid composition containing glucose in a proportion of 0.005 to 0.2 w / v% The polymer polymerized with
The ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
(A) The ratio of component (B-2) to 100 parts by weight of component is 0.1 parts by weight or more, or
(B) component, (B-2) component, or (B), characterized in that the ratio of component (B-3) to 100 parts by weight of component (A) is 1 part by weight or more. -3) A method for suppressing the formation of precipitates of an ophthalmic liquid composition containing a component.

  In these methods, the component (A), the component (B-1), the component (B-2) or the component (B-3) used, the content ratio and ratio thereof, the types of other components added, The content ratio, the formulation form of the ophthalmic liquid composition, the type of the container for storing the ophthalmic liquid composition, and the like are the same as those described in “1. Ophthalmic liquid composition-1”.

5. Method for inhibiting bacterial adhesion to SCL, method for imparting bacterial adhesion inhibiting action to SCL In addition, as described above, by using the components (A) and (B) together, bacterial adhesion to SCL can be significantly suppressed. . Therefore, the present invention also provides methods of the following embodiments III-1 and III-2 from another viewpoint.
III-1. (A) a polymer obtained by polymerizing the monomer represented by formula (I) alone or with another copolymerizable monomer, and (B) at least one of chondroitin sulfate, hyaluronic acid, a salt thereof, and glucose A method for inhibiting bacterial adhesion to SCL, comprising contacting an ophthalmic liquid composition containing a seed with SCL.
III-2. In the ophthalmic liquid composition, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B) chondroitin sulfate, hyaluronic acid, A method for imparting an action of inhibiting bacterial adhesion to SCL to the ophthalmic liquid composition, comprising using these salts and at least one of glucose in combination.

  In these methods, the types and content ratios and ratios of the components (A) and (B) to be used, the types and content ratios of other components, the formulation form of the ophthalmic liquid composition, and the ophthalmic liquid composition The type of container to be accommodated is the same as in “2. Ophthalmic liquid composition-2”.

6). A method for improving the wettability of SCL, a method for imparting an action for improving the wettability of SCL, and , as described above, the wettability of SCL can be improved by using the components (A) and (B) together. Accordingly, the present invention also provides methods of the following embodiments IV-1 and IV-2 from another viewpoint.
IV-1. (A) a polymer obtained by polymerizing the monomer represented by formula (I) alone or with another copolymerizable monomer, and (B) at least one of chondroitin sulfate, hyaluronic acid, a salt thereof, and glucose A method for improving the wettability of SCL, comprising bringing an ophthalmic liquid composition containing seeds into contact with SCL.
IV-2. In the ophthalmic liquid composition, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, (B) chondroitin sulfate, hyaluronic acid, A method for imparting an effect of improving the wettability of SCL to the ophthalmic liquid composition, comprising using these salts and at least one of glucose in combination.

  In these methods, the types and content ratios and ratios of the components (A) and (B) to be used, the types and content ratios of other components, the formulation form of the ophthalmic liquid composition, and the ophthalmic liquid composition The type of container to be accommodated is the same as in “2. Ophthalmic liquid composition-2”.

7). Method for cleaning pollen protein adhering to ionic SHCL, method for imparting cleaning action to pollen protein adhering to ionic SHCL Also, as described above, by using both (A) and (B) components in combination, An excellent cleaning effect can be exerted on pollen proteins adhering to SHCL. Accordingly, the present invention also provides methods of the following embodiments V-1 and V-2 from another viewpoint.
V-1. (A) a polymer obtained by polymerizing the monomer represented by formula (I) alone or with another copolymerizable monomer, and (B) at least one of chondroitin sulfate, hyaluronic acid, a salt thereof, and glucose A method for washing pollen protein adhering to ionic SHCL, comprising contacting an ophthalmic liquid composition comprising a seed with ionic SHCL.
V-2. In the ophthalmic liquid composition, (A) a polymer obtained by polymerizing the monomer represented by the general formula (I) alone or with another monomer capable of copolymerization, and (B) chondroitin sulfate, hyaluronic acid, A method for imparting to the ophthalmic liquid composition a cleaning action on pollen proteins adhering to ionic SHCL, wherein these salts and at least one of glucose are used in combination.

  In these methods, the types and content ratios and ratios of the components (A) and (B) to be used, the types and content ratios of other components, the formulation form of the ophthalmic liquid composition, and the ophthalmic liquid composition The type of container to be accommodated is the same as in “2. Ophthalmic liquid composition-2”.

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

Test Example 1A: Evaluation test for running out of liquid from nozzle (1)
A 13 mL polyethylene ophthalmic container made of polyethylene terephthalate is filled with 13 mL each of the test solutions prepared in accordance with Tables 1 and 2 (Examples 1-1 to 1-11 and Comparative Examples 1-1 to 1-9). A polyethylene nozzle was attached. Separately, the filter paper was accommodated in the measurement container, the lid was closed and sealed, and the total weight (initial value) of the filter paper and the measurement container was measured. One drop of the test solution was dropped with the angle of the nozzle of the eye drop container horizontal (container turned sideways). Next, the lid of the measurement container is opened, and the liquid adhering to the outside of the nozzle after dropping one drop in the measurement container is sucked up by the stored filter paper, and then the filter paper from which the liquid has been sucked is stored in the measurement container. In the state, the lid of the measurement container was closed and sealed. After repeating this for 20 drops, measure the total weight of the filter paper and the measuring container from which the liquid was sucked, subtract the initial value, and add the total weight of the liquid attached to the outside of the nozzle by dropping 20 drops (nozzle attached liquid amount ( mg / 20 times)).

  The obtained results are shown in FIGS. In Comparative Example 1-1 in which no MPC polymer was blended, there was almost no adhesion of the test liquid to the nozzle, but in Comparative Examples 1-2, 1-3 and 1-4 in which MPC polymer was blended, the borate buffer Regardless of the presence or absence of the nozzle, the amount of nozzle adhesion liquid increased remarkably. In addition, when chondroitin sodium sulfate, sodium hyaluronate, or glucose is blended with a borate buffer without blending MPC polymer (Comparative Examples 1-5, 1-7, and 1-9), borate buffer Compared with the case where only the agent was blended (Comparative Example 1-1), the amount of the nozzle adhesion liquid was slightly increased.

  On the other hand, when MPC polymer is mixed with sodium chondroitin sulfate, sodium hyaluronate, or glucose (Examples 1-1 to 1-11), these are not included (Comparative Examples 1-3, 1- Compared to 4), it was found that the amount of nozzle deposit liquid was significantly reduced. Furthermore, in the case of containing ethylenediaminetetraacetate sodium in addition to the MPC polymer and sodium hyaluronate (Example 1-4), compared with the case of not containing ethylenediaminetetraacetate sodium (Example 1-3), further nozzle liquid It was also confirmed that the amount of adhesion was reduced. Similarly, in the case of containing sodium chloride in addition to the MPC polymer and sodium hyaluronate (Example 1-8), the amount of nozzle liquid adhesion was further reduced compared to the case of not containing sodium chloride (Example 1-2). It was also confirmed to decrease.

  In addition, during the test, in Examples 1-1 to 1-11 and Comparative Examples 1-1, 1-5, 1-7, and 1-9, the liquid breakage during the dropping was good, Comparative Example 1 It was also realized that the liquid breakage during the dripping was poor for 2 to 1-4, 1-6, and 1-8.

  Based on the above results, in the ophthalmic liquid composition, by blending chondroitin sulfate, hyaluronic acid, their salts and / or glucose together with MPC polymer, the liquid after the instillation is good and the quality is maintained. It was revealed that an excellent preparation can be provided.

Test Example 1B: Evaluation test for running out of liquid from nozzle (2)
From the results of Test Example 1A, it was confirmed that the combined use of MPC polymer and sodium chondroitin sulfate at a specific ratio reduces the amount of nozzle liquid adhesion and improves the nozzle liquid drop after instillation. Therefore, in this test, in order to analyze in more detail the effect of the content and content ratio of MPC polymer and sodium chondroitin sulfate on nozzle runout after instillation, the test solutions shown in Table 3 (Examples 1-12) 1-21 and Comparative Examples 1-10 to 1-12) were prepared and tested in the same manner as in Test Example 1A. Moreover, it tested similarly about the control test liquid of the same composition as the Example or comparative example shown in Table 3 except not containing chondroitin sulfate Na. In this test example, the adhesion suppression rate (%) was calculated from the measured nozzle adhesion liquid amount according to the following calculation formula.

  Table 4 shows the obtained results. Table 4 also shows the results of Examples 1-1, 1-6, 1-7 and Comparative Example 1-6 in Test Example 1A. When sodium chondroitin sulfate was less than 0.05 w / v% (Comparative Examples 1-10 and 1-6), adhesion of the liquid to the nozzle could not be suppressed. Further, even when the chondroitin sulfate Na is 0.05 w / v% or more, the chondroitin sulfate Na is less than 5 parts by weight per 100 parts by weight of the MPC polymer (Comparative Example 1-11), and the chondroitin sulfate Na is 0.5 w / v. Even in the case where the ratio exceeds 10% (Comparative Example 1-12), the adhesion of the liquid to the nozzle could not be suppressed. On the other hand, when chondroitin sulfate Na is 0.05 to 0.5 w / v% and chondroitin sulfate Na is more than 5 parts by weight per 100 parts by weight of MPC polymer, it effectively suppresses liquid adhesion to the nozzle. Was done.

  Further, when a borate buffer is used as a buffer (Example 1-1), the adhesion inhibition rate is higher than when a phosphate buffer is used (Example 1-18). It was also revealed that the effect of suppressing the adhesion of the liquid to the nozzle becomes more prominent by adding a boric acid buffer.

Test Example 1C: Liquid breakage evaluation test from nozzle (3)
From the results of Test Example 1A above, it was confirmed that the combined use of MPC polymer and sodium hyaluronate at a specific ratio reduces the amount of nozzle liquid adhesion and improves the liquid drainage of the nozzle after instillation. Therefore, in this test, in order to further analyze the effect of the content and content ratio of the MPC polymer and sodium hyaluronate on the liquid running out of the nozzle after instillation, the test liquids shown in Table 5 (Examples 1-22) To 1-30 and Comparative Examples 1-13 to 1-15) were prepared and tested in the same manner as in Test Example 1A. Moreover, except not containing hyaluronic acid Na, it tested similarly about the control test liquid of the same composition as the Example shown in Table 5, or a comparative example, and according to the same calculation formula as the said test example 1B, adhesion inhibitory rate (%) Was calculated.

  The results obtained are shown in Table 6. Table 6 also shows the results of Examples 1-2, 1-3, 1-4, 1-8, 1-9 and Comparative Example 1-8 in Test Example 1A. When sodium hyaluronate was less than 0.002 w / v% (Comparative Examples 1-8 and 1-13), adhesion of the liquid to the nozzle could not be suppressed. Moreover, even if sodium hyaluronate is 0.002 w / v% or more, when sodium hyaluronate is less than 0.1 parts by weight per 100 parts by weight of MPC polymer (Comparative Example 1-14), and sodium hyaluronate is 0.1 w / v Even in the case of exceeding% (Comparative Example 1-15), adhesion of the liquid to the nozzle could not be suppressed. On the other hand, when sodium hyaluronate is 0.002 to 0.1 w / v% and sodium hyaluronate is more than 0.1 parts by weight per 100 parts by weight of MPC polymer, it effectively suppresses the adhesion of the liquid to the nozzle. Was done.

  In addition, when a borate buffer is used as a buffer (Example 1-2), the adhesion inhibition rate is higher than when a phosphate buffer is used (Example 1-25). As with the results of Test Example 1B, it has also been clarified that the effect of suppressing the liquid adhesion to the nozzle becomes even more pronounced by the incorporation of the boric acid buffer.

Test Example 1D: Evaluation test for running out of liquid from nozzle (4)
From the results of Test Example 1A, it was confirmed that the amount of nozzle liquid adhesion decreased by using the MPC polymer and glucose together at a specific ratio, and the nozzle liquid after instillation was improved. Therefore, in this test, the test solutions shown in Table 7 (Examples 1-31 to 1) were used in order to analyze in more detail the effects of the content and content ratio of MPC polymer and glucose on the nozzle runout after instillation. -37 and Comparative Examples 1-16 to 1-18) were prepared and tested in the same manner as in Test Example 1A. Moreover, except not containing glucose, also about the control test liquid of the same composition as the Example or comparative example shown in Table 7, it tests similarly, According to the same calculation formula as the said test example 1B, adhesion inhibitory rate (% ) Was calculated.

  Table 8 shows the obtained results. Table 8 also shows the results of Examples 1-5, 1-10, and 1-11 in Test Example 1A. When glucose was less than 0.005 w / v% (Comparative Example 1-16), liquid adhesion to the nozzle could not be suppressed. Moreover, even when glucose is 0.005 w / v% or more, when glucose is less than 1 part by weight per 100 parts by weight of MPC polymer (Comparative Example 1-17), and when glucose is more than 0.2 w / v% (comparison) Even in Example 1-18), the adhesion of the liquid to the nozzle could not be suppressed. On the other hand, when glucose was 0.005 to 0.2 w / v% and glucose satisfied 1 part by weight or more per 100 parts by weight of MPC polymer, the adhesion of the liquid to the nozzle could be effectively suppressed. .

  In addition, when a borate buffer is used as a buffer (Example 1-5, etc.), the adhesion inhibition rate is higher than when a phosphate buffer is used (Example 1-37). As with the results of Test Examples 1B and 1C, it was also revealed that the effect of suppressing the adhesion of the liquid to the nozzle becomes more prominent by the addition of the boric acid buffer.

Reference test example 1: Evaluation test for running out of liquid from nozzle (5)
Test solutions (Reference Example 1-2) shown in Table 9 were prepared and tested in the same manner as in Test Example 1A. Further, a control test solution having the same composition as the reference example shown in Table 9 except that tetrahydrozoline hydrochloride and allantoin are not contained was also tested in the same manner, and the adhesion inhibition rate (% ) Was calculated.

  The results are also shown in Table 9. From this result, even when tetrahydrozoline hydrochloride or allantoin was added together with the MPC polymer, the effect of suppressing liquid adhesion to the nozzle was not recognized. That is, the liquid adhesion inhibitory effect confirmed in Test Examples 1A to 1D is a unique effect observed when a combination of MPC polymer and chondroitin sulfate, hyaluronic acid, their salts, and / or glucose is selected. It became clear that there was.

Test Example 2: Precipitation Inhibition Test In accordance with the formulation described in Table 10, each component was dissolved in sterilized purified water to make a total volume of 100 mL of test solution (Examples 2-1 to 2-3 and Comparative Examples 2-1 to 2-3) was prepared.

After dropping each test solution 100 μL on a slide glass and leaving it at room temperature for three nights, the state of each test solution was visually observed to evaluate the degree of precipitate formation according to the following evaluation criteria. .
<Degree of precipitate formation>
−: No precipitate was deposited. +: A very small amount of white solid was deposited (thin, the outline of the dried portion of the droplet was unclear. There was no significant precipitation in the center).
++: Precipitation of a small amount of white solid was observed (the outline of the dried portion of the droplet was clear. There was no remarkable precipitation at the center)
++++: Precipitation of white solids was observed (the outline of the dried portion of the droplets was clear. The central part was also markedly precipitated)

  The results are also shown in Table 10. As a result, precipitation of white crystals was observed when sodium chondroitin sulfate, sodium hyaluronate, or glucose was added alone (Comparative Examples 2-1 to 2-3). In particular, when sodium hyaluronate was blended (Comparative Example 2-2), the formation of precipitates was significant. On the other hand, it was confirmed that when chondroitin sulfate sodium, sodium hyaluronate, or glucose was added in combination with MPC polymer (Examples 2-1 to 2-3), the formation of precipitates could be suppressed.

  Considering that the ophthalmic liquid composition tends to adhere to the edge and eyelashes of the eye during use, suppressing the formation of precipitates is effective in maintaining the cosmetic appearance of the user. Therefore, it was also confirmed from this test result that a preparation that meets the user's request for maintaining a cosmetic appearance can be provided by using MPC polymer in combination with sodium chondroitin sulfate, sodium hyaluronate, or glucose. .

Test Example 3A: Bacterial adhesion suppression test for contact lens (1)
Using the test solutions shown in Table 11 (Examples 3-1 to 3-2 and Comparative Examples 3-1 to 3-4), Pseudomonas aeruginosa (ATCC9027) into SCL (SCL classification: Group IV, main material: etafilconA) ) (Bacteria) adhesion was evaluated.

Each lens was immersed in 5 mL of sterile physiological saline overnight (lens pretreatment). 1 mL of each test solution was placed in a 24-well multiplate, and one lens was placed in each. As a control, physiological saline was used (n = 5). After 24 hours, lightly absorb the water from each lens with a non-woven fabric, and then place it in a 6-well multiplate containing 5 mL of 10 ^6-7 CFU / mL Pseudomonas aeruginosa bacterial solution (suspended in physiological saline) for 30 minutes. Stored at room temperature. Next, each lens was placed in a 6-well plate containing 5 mL of physiological saline with tweezers and shaken for 1 minute. Transfer the lens to a Spitz tube containing 5 mL of new physiological saline, apply ultrasonic waves (38 kHz) for 3 minutes, and then stir with a test tube mixer for 1 minute to remove the bacteria attached to each SCL and attach the bacteria. A liquid was used.

  The obtained adherent bacterial solution is diluted to an appropriate concentration, seeded on soy bean, casein, digest, agar medium (SCDLP agar medium) and cultured overnight at 33 ° C. By counting, the number of viable bacteria attached to each lens was determined.

  The results are shown in FIG. It was confirmed that when the MPC polymer was blended (Comparative Example 3-2), the amount of bacteria attached to SCL was increased compared to the control or Comparative Example 3-1. On the other hand, it was found that when chondroitin sulfate sodium or sodium hyaluronate was blended with the MPC polymer (Examples 3-1 and 3-2), bacterial adhesion to the soft contact lens was significantly reduced. .

  Soft contact lenses containing MPC polymer as a constituent material are known to have an effect of suppressing bacterial adhesion to the lens, but when MPC polymer is brought into contact with the lens as an ophthalmic liquid composition component, It was confirmed that alone, it did not exhibit the effect of inhibiting bacterial adhesion, but rather tended to increase the adhesion of bacteria.

  From the above results, it has been clarified that an excellent preparation capable of suppressing bacterial adhesion to a soft contact lens can be provided by using an MPC polymer in combination with sodium chondroitin sulfate or sodium hyaluronate.

  Based on this test result, the bacterial adhesion suppression rate (%) to the contact lens was calculated according to the same calculation formula as in Test Example 3B below. As a result, the bacterial adhesion suppression rate of Example 3-1 was 19.9%. The bacterial adhesion inhibition rate of 3-2 was 56.2%. In addition, Comparative Example 3-3 was used as the control of Example 3-1, and Comparative Example 3-4 was used as the control of Example 3-2.

Test Example 3B: Bacterial adhesion suppression test for contact lens (2)
In Test Example 3A, the effect of suppressing the adhesion of bacteria to contact lenses was observed by the combined use of MPC polymer and sodium chondroitin sulfate (Example 3-1). Then, the influence which the change of the content rate of a MPC polymer and sodium chondroitin sulfate and the change of the content rate of a borate buffer has on the adhesion prevention effect to a contact lens was evaluated. Specifically, test solutions (Examples 3-3 to 3-7) shown in Table 12 were prepared and tested in the same manner as in Test Example 3A. Moreover, the test was similarly performed also about the control test liquid of the same composition as the Example shown in Table 12 except not containing MPC polymer. From the measured number of viable bacteria, the bacterial adhesion inhibition rate (%) was calculated according to the following calculation formula.

  The obtained results are also shown in Table 12. From these results, it was confirmed that even if the content ratio of MPC polymer and sodium chondroitin sulfate was changed or the concentration of borate buffer was changed, the effect of inhibiting the adhesion of bacteria to contact lenses was effectively achieved. It was.

Test Example 3C: Bacterial adhesion suppression test for contact lens (3)
In Test Example 3A, the effect of suppressing the adhesion of bacteria to the contact lens was confirmed by the combined use of MPC polymer and sodium hyaluronate (Example 3-2). Then, the influence which the change of the content rate of a MPC polymer and sodium hyaluronate and the change of the content rate of a borate buffer has on the adhesion inhibitory effect to a contact lens was evaluated. Specifically, test solutions (Examples 3-8 to 3-12) shown in Table 13 were prepared and tested by the same method as in Test Example 3A. Moreover, except not containing MPC polymer, it tested similarly about the control test liquid of the same composition as the Example shown in Table 13, and according to the same calculation formula as the said Test Example 3B, bacteria adhesion suppression rate (%) Was calculated.

  The obtained results are also shown in Table 13. From this result, it was confirmed that even if the content ratio of the MPC polymer and sodium hyaluronate was changed or the concentration of the boric acid buffer was changed, the adhesion of bacteria to the contact lens could be effectively suppressed.

Test Example 3D: Bacteria adhesion suppression test for contact lens (4)
The effect of combined use of MPC polymer and glucose on the adhesion of bacteria to contact lenses was evaluated. Specifically, test solutions (Examples 3-13 to 3-16) shown in Table 14 were prepared and tested in the same manner as in Test Example 3A. Moreover, except not containing MPC polymer, also about the control test liquid of the same composition as the Example shown in Table 14, it tests similarly and according to the same calculation formula as the said Test Example 3B, bacteria adhesion suppression rate (%) Was calculated.

  The obtained results are also shown in Table 14. From this result, it was confirmed that the adhesion of bacteria to the contact lens can be suppressed by using the MPC polymer and glucose together.

Reference test example 2: bacterial adhesion suppression test for contact lens (5)
Test solutions (Reference Example 3-4) shown in Table 15 were prepared and tested in the same manner as in Test Example 3A. Moreover, except not containing MPC polymer, also about the control test liquid of the same composition as the reference example shown in Table 15, it tests similarly, According to the same calculation formula as the said test example 3B, bacteria adhesion suppression rate (%) Was calculated.

  The results are also shown in Table 15. As is clear from this result, when pyridoxine hydrochloride or taurine is added together with MPC polymer, the adhesion of bacteria to the contact lens cannot be suppressed, but rather, the adhesion of the bacteria to the contact lens is increased. . That is, the effect of suppressing the adhesion of bacteria to the contact lenses confirmed in Test Examples 3A to 3D is observed when a combination of MPC polymer and chondroitin sulfate, hyaluronic acid, salts thereof, and / or glucose is selected. It became clear that this was a unique effect.

Test Example 4: SCL wettability test In accordance with the formulation described in Table 16, each component was dissolved in purified water to make a total volume of 100 mL, and the test solutions (Example 4-1 and Comparative Examples 4-1 to 4-3) were used. Prepared.

  Next, SCL (SCL classification: Group III, main material: Balafilcon A, ionic SHCL) was immersed one by one in 5 mL of the test solution and allowed to stand at room temperature for 24 hours.

  Thereafter, water on the lens surface was gently wiped off, and 1 μL of physiological saline was dropped on the lens surface using a contact angle measuring device (Drop Master 500) and analysis software (FAMAS) (both manufactured by Kyowa Interface Science Co., Ltd.). The contact angle was measured.

  The measurement was performed 5 times per sheet. Measurement points were taken every 500 ms up to 2500 ms, and the contact angle at 1500 ms was adopted.

  The results are shown in FIG. It is shown that the smaller the contact angle, the more easily the surface of the SCL gets wet and the feeling of wearing improves. As a result, in the case of sodium chondroitin sulfate alone (Comparative Example 4-3), the contact angle increased and the wettability tended to deteriorate. On the other hand, in the case of the MPC polymer alone (Comparative Example 4-2), a slight wettability improving effect was observed. On the other hand, when MPC polymer and sodium chondroitin sulfate were used in combination (Example 4-1), it was found that the wettability was remarkably improved.

  Although MPC polymer is known to improve wettability for hard contact lenses (JP 2000-98310 A, etc.), the wettability improvement effect for SCL is not known. It was found that the wettability improvement effect was small.

  From this test result, it became clear that the combined use of MPC polymer and sodium chondroitin sulfate can improve the wettability to SCL and provide a preparation that improves the wearing feeling of SCL.

Reference Test Example 3: Pollen protein washing test for SCL Four types of SCL shown in Table 17 were used in the test to evaluate the pollen protein adsorption characteristics for SCL.

  First, the lenses used for the test were immersed one by one in 4 mL of physiological saline and stored overnight at room temperature (lens pretreatment).

Pollen protein antigen (Cel Pollen Extract-Ja, manufactured by LSL Co., Ltd., property: freeze-dried powder (Cedar Pollen crude extract Mountain ceder , extracted from pollen of Juniperus Asheii )) dissolved in physiological saline 5 mg / 30 mL pollen protein solution was prepared. In each hole of the 24-well plate, 1.0 mL of pollen protein solution was put, and after wiping off excess moisture from the pretreated lens, it was immersed and shaken at 34 ° C. and 120 rpm for 18 hours. Next, take out the lens, quickly soak (about 1 second) in 100 mL of physiological saline, rinse the excess liquid, and then lightly drain the water using the edge of a beaker, then put the pollen protein into each hole of the 24-well plate. It was immersed in 1 mL of separation liquid (aqueous solution containing 1% sodium carbonate and 1% SDS). The mixture was shaken at 34 ° C. and 120 rpm for 3 hours to separate the pollen protein adsorbed on the lens into the pollen protein separation solution.

  Using a micro BCA assay kit (Thermo SCIENTIFIC, Pierce # 23235), the amount of pollen protein in the pollen protein separation solution was quantified as an albumin equivalent value to determine the amount of pollen protein adsorbed to the lens.

  The results are shown in FIG. When lens A, which is ionic SHCL, is used, the adsorption of pollen protein is significantly higher than lenses C and D, which are non-silicone SCL, and lens B, which is nonionic SHCL. It was. From these results, it was confirmed that pollen protein has a strong tendency to adsorb to ionic SHCL among soft contact lenses, and ionic SHCL has a specific problem of pollen protein adsorption.

Test Example 5: Pollen protein washing test for ionic SHCL The following test was carried out using lens A (ionic SHCL) in which significant adsorption of pollen protein was confirmed in Reference Test Example 3 above.

First, lenses A were immersed one by one in 5 mL of physiological saline and stored overnight at room temperature (lens pretreatment). Pollen protein antigen (CEL Pollen Extract-Ja, manufactured by L.S.L. Co., Ltd.): Lyophilized powder (Cedar Pollen crude extract Mountain ceder , extracted from pollen of Juniperus Asheii )) in physiological saline, A 5 mg / 50 mL pollen protein solution was prepared. In each hole of the 24-well plate, 1.0 mL of pollen protein solution was added, and the excess water of the pretreated lens was wiped and immersed, and shaken at 34 ° C. and 120 rpm / min for 8 hours.

  The lens A immersed in the pollen protein solution was taken out, quickly immersed (about 1 second) in 100 mL of physiological saline, rinsed with excess liquid, wiped off moisture, and placed in a 24-well plate. The sample was immersed in the test solutions (Examples 5-1 to 5-5 and Comparative Examples 5-1 to 5-2) and shaken at 34 ° C. and 120 rpm / min for 15 hours. After that, lens A is taken out, soaked quickly (about 1 second) in 100 mL of physiological saline, rinsed the excess liquid, and then lightly drained with a beaker edge and separated into pollen protein in a 24-well plate. It was immersed in 0.5 mL of the liquid for use (aqueous solution containing 1% sodium carbonate and 1% SDS). The mixture was shaken at 34 ° C. and 120 rpm for 3 hours to separate the pollen protein adsorbed on the lens into the pollen protein separation solution.

  Using a micro BCA assay kit (Thermo SCIENTIFIC, Pierce # 23235), the amount of pollen protein in the pollen protein separation solution was quantified as an albumin equivalent value, and the amount of pollen protein adsorbed on lens A was determined. From the following formula, the improvement rate of pollen protein adsorption in other Comparative Examples and Examples relative to the pollen protein adsorption amount of Comparative Example 5-1 was calculated.

  The results are also shown in Table 18. From this result, when MPC polymer was used in combination with sodium chondroitin sulfate, sodium hyaluronate, or glucose (Examples 5-1 to 5-5), it was compared with the case of MPC polymer alone (Comparative Example 5-2). As a result, it was confirmed that the amount of pollen remaining on the lens was extremely small. That is, in Examples 5-1 to 5-5, it became clear that the cleaning effect of pollen adsorbed on the lens was high. Considering that chondroitin sulfate sodium, sodium hyaluronate and glucose are not known to have a protein cleaning effect in SCL, the results of this test are quite surprising. It was also confirmed that when boric acid and borax were used as buffering agents, the cleaning effect on pollen protein was further enhanced.

  From the above results, it has been clarified that a combination of MPC polymer and sodium chondroitin sulfate or sodium hyaluronate can provide a preparation having an excellent pollen cleaning effect for ionic SHCL.

Formulation Example In the formulation described in Table 19-21, eye drops (Examples 6-7, 19-20, and 32-33), eye drops for contact lenses (Examples 8-16, 21-29, and 34-) 42), contact lens mounting fluids (Examples 17, 30, and 43) and eyewashes (Examples 18, 31, and 44) are prepared.

  Among these formulation examples, Examples 6-7, 14-20, 27-33 and 40-44 are embodiments of the ophthalmic liquid composition-1 of the present invention. Examples 8-18, 21 -31 and 34-44 are exemplary embodiments of the ophthalmic liquid composition-2 of the present invention. In addition, the MPC polymer blended in Examples 6-14, 17-25, 28-36, and 39-44 is the same as that used in Table 1. In addition, the MPC polymer blended in Examples 15-16, 26-27, and 37-38 has a MPC polymer concentration of a prescribed amount using a trade name “LIPIDURE-HM” (manufactured by NOF Corporation). So formulated.

Claims (13)

(A) A polymer having only a monomer represented by the general formula (I), having a weight average molecular weight of 5,000 to 2,000,000, and / or
A copolymer of the monomer represented by the general formula (I) and the monomer represented by the general formula (II), wherein the constituent ratio of the monomer of the general formula (I) with respect to the total amount of the copolymer is 50 to 95 mol. %, And a copolymer having a weight average molecular weight of 5,000 to 2,000,000 ,

[Wherein, n1 is an integer of 2 to 4, R ₁ is a hydrogen atom or a methyl group, R ₂ is a group represented by — (R ₆ O) _n2 —R ₆ — (R ₆ has 1 to 4 carbon atoms] And n2 represents an integer of 0 to 5), and R _{3 to} R ₅ are the same or different and represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. ]

[Wherein, R ₇ represents a hydrogen atom or a methyl group, and R ₈ represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms. ]
(B-1) Chondroitin sulfate having a viscosity average molecular weight of 10,000 to 500,000 and at least one of its salts, (B-2) Hyaluronic acid having a viscosity average molecular weight of 10,000 to 5,000,000 And at least one of its salts, or (B-3) glucose,
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
The content ratio of the component (B-3) is 0.005 to 0.2 w / v%, and the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more, Ophthalmic liquid composition. The ophthalmic liquid composition according to claim 1, wherein the component (A) is a copolymer of 2-methacryloyloxyethyl phosphorylcholine and butyl methacrylate. The ophthalmic liquid composition according to claim 1 or 2, wherein the content of component (A) is 0.0001 to 5 w / v%. The ophthalmic liquid composition according to any one of claims 1 to 3, which is an eye drop or a contact lens mounting liquid. The ophthalmic liquid composition according to any one of claims 1 to 4, further comprising at least one selected from the group consisting of (C-1) ethylenediamineacetic acid, derivatives thereof, and salts thereof. Furthermore, the ophthalmic liquid composition in any one of Claims 1-5 containing sodium chloride as (C-2) component. Furthermore, the ophthalmic liquid composition in any one of Claims 1-6 containing a buffering agent as (D) component. Furthermore, the ophthalmic liquid composition in any one of Claims 1-7 containing at least 1 sort (s) selected from the group which consists of a fragrance | flavor and a refreshing agent, and a high molecular compound, a cellulose, and those derivatives. The ophthalmic liquid composition according to any one of claims 1 to 8 , which is contained in a container equipped with a polyethylene nozzle. (A) A polymer having only a monomer represented by the general formula (I), having a weight average molecular weight of 5,000 to 2,000,000, and / or
A copolymer of the monomer represented by the general formula (I) and the monomer represented by the general formula (II), wherein the constituent ratio of the monomer of the general formula (I) with respect to the total amount of the copolymer is 50 to 95 mol. %, And a copolymer having a weight average molecular weight of 5,000 to 2,000,000 ,

[ Wherein, n1 and R _{1 to} R ₅ are the same as described above. ]

[Wherein, R ₇ and R ₈ are the same as described above. ]
As component (B ), (B-1) chondroitin sulfate having a viscosity average molecular weight of 10,000 to 500,000 and at least one of its salts , (B-2) a viscosity average molecular weight of 10,000 to 5 million hyaluronic acid and at least one in a salt thereof, and (B-3) and at least one in the glucose seen including,
The content ratio of component (A) is 0.0001 to 5 w / v%, and
(B-1) component content is 0.05-0.5 w / v%,
(B-2) component content is 0.002 to 0.1 w / v%, and / or
(B-3) component content is 0.005 to 0.2 w / v%
And characterized in that, ophthalmic liquid composition for soft contact lenses. Furthermore, the ophthalmic liquid composition of Claim 10 which contains a buffer as (D) component. Furthermore, the ophthalmic liquid composition for soft contact lenses of Claim 10 or 11 containing at least 1 sort (s) selected from the group which consists of a fragrance | flavor and a refreshing agent, and a high molecular compound, cellulose, and derivatives thereof. In an ophthalmic liquid composition,
(A) A polymer having only a monomer represented by the general formula (I), having a weight average molecular weight of 5,000 to 2,000,000, and / or
A copolymer of the monomer represented by the general formula (I) and the monomer represented by the general formula (II), wherein the constituent ratio of the monomer of the general formula (I) with respect to the total amount of the copolymer is 50 to 95 mol. %, And a copolymer having a weight average molecular weight of 5,000 to 2,000,000 ,
(B-1) Chondroitin sulfate having a viscosity average molecular weight of 10,000 to 500,000 and at least one of its salts, (B-2) Hyaluronic acid having a viscosity average molecular weight of 10,000 to 5,000,000 And at least one of its salts, or (B-3) glucose,
The content ratio of the component (B-1) is 0.05 to 0.5 w / v%, and the ratio of the component (B-1) to 100 parts by weight of the component (A) is 5 parts by weight or more,
The content ratio of the component (B-2) is 0.002 to 0.1 w / v%, and the ratio of the component (B-2) to 100 parts by weight of the component (A) is 0.1 parts by weight or more, or
(B-3) The content ratio of the component is 0.005 to 0.2 w / v%, and it is used in combination so that the ratio of the component (B-3) to 100 parts by weight of the component (A) is 1 part by weight or more. wherein, in the eye department liquid composition, imparting effect solution break from the nozzle is improved.

[Wherein, n1 and R _{1 to} R ₅ are the same as described above. ]

[Wherein, R ₇ and R ₈ are the same as described above. ]

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