JP5984531B2 - Aqueous ophthalmic composition - Google Patents

Description

  The present invention relates to an aqueous ophthalmic composition. More specifically, the present invention relates to an aqueous ophthalmic composition in which generation of precipitates is suppressed and light stability is improved.

  In the ophthalmic field, solubilizers are incorporated in many formulations. In particular, in an aqueous ophthalmic composition, various solubilizing agents have been devised for the purpose of assisting dissolution of physiologically active components and additives having relatively low water solubility. One of the solubilizing agents used in the ophthalmic field is a surfactant. Polyoxyethylene castor oil is a kind of nonionic surfactant and is known to be blended into an aqueous ophthalmic composition for the purpose of assisting dissolution of other blended components (Patent Document 1).

  In addition, chondroitin sulfate and its salts have been conventionally used for the purpose of promoting energy metabolism, promoting metabolism and cell respiration to relieve eye fatigue, or supplementing tear fluid components. (Patent Document 2).

  On the other hand, in order to improve the physical properties of the aqueous ophthalmic composition, blending of various components has been attempted. For example, Patent Document 3 discloses a mucosa-applied composition containing sesame oil as a method for stabilizing the viscosity of the composition. Furthermore, vitamin A has been used in ophthalmic compositions for the purpose of eliminating eye fatigue by accelerating the metabolism and cell respiration of eye cells and exerting anti-inflammatory effects. (Patent Document 4).

  However, when the above-mentioned components are contained in an aqueous ophthalmic composition containing polyoxyethylene castor oil, the effects on the generation of precipitates and light stability have not been clarified so far. In particular, when these components and a specific surfactant are contained in an aqueous ophthalmic composition, it is currently difficult to predict what effect will be exerted on the aqueous ophthalmic composition. is there.

JP 2005-298448 A JP 2011-148791 A JP 2006-117656 A JP 2009-173638 A

  As a result of various studies on an aqueous ophthalmic composition containing polyoxyethylene castor oil, the present inventors have found that an aqueous ophthalmic composition containing polyoxyethylene castor oil and further containing chondroitin sulfate and / or a salt thereof. Then, it confirmed that the precipitate was easy to produce. Generation | occurrence | production of the precipitate in an aqueous ophthalmic composition causes the fall of quality including safety | security, and the fall of a commercial value, Therefore Controlling this is a very important subject.

  Accordingly, an object of the present invention is to provide an aqueous ophthalmic composition containing polyoxyethylene castor oil and chondroitin sulfate and / or a salt thereof, in which generation of precipitates is suppressed, and It is providing the method of suppressing generation | occurrence | production of the deposit in an aqueous ophthalmic composition.

  In addition, according to studies by the present inventors, it has been confirmed that an aqueous ophthalmic composition containing polyoxyethylene castor oil is likely to decompose polyoxyethylene castor oil when exposed to light. The photodecomposition of the components contained in the aqueous ophthalmic composition leads to a decrease in quality including safety and a decrease in commercial value, and further prevents the components from exhibiting their inherent performance, thereby suppressing photodegradation. This is a very important issue.

  Accordingly, another object of the present invention is to provide an aqueous ophthalmic composition having improved light stability in an aqueous ophthalmic composition containing polyoxyethylene castor oil, and the light stability of the aqueous ophthalmic composition. It is to provide a way to improve.

  The inventors of the present invention have made extensive studies to solve the above problems. As a result, the aqueous ophthalmic composition containing polyoxyethylene castor oil (hereinafter sometimes referred to as “component (A)”) is at least one selected from the group consisting of chondroitin sulfate and salts thereof (hereinafter “(B) Component (A) and component (B) by blending at least one selected from the group consisting of sesame oil and vitamin A (hereinafter sometimes referred to as “component (C)”) The present inventors have found that the generation of precipitates that are contained in the aqueous ophthalmic composition can be suppressed, and further, the photodecomposition of the component (A) can be suppressed to improve the light stability in the aqueous ophthalmic composition.

  The present invention has been completed as a result of further research based on these findings.

That is, this invention provides the aqueous ophthalmic composition of the aspect hung up below.
Item 1-1. An aqueous ophthalmic composition comprising (A) polyoxyethylene castor oil, (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, and (C) at least one selected from the group consisting of sesame oil and vitamin A object.
Item 1-2. The aqueous ophthalmic composition according to Item 1-1, wherein the component (A) is polyoxyethylene castor oil having an average addition mole number of ethylene oxide of 2 to 70.
Item 1-3. The aqueous ophthalmic composition according to Item 1-1 or 1-2, wherein the component (A) is polyoxyethylene castor oil having an average addition mole number of ethylene oxide of 2 to 35.
Item 1-4. Item 4. The aqueous ophthalmic composition according to any one of Items 1-1 to 1-3, wherein the total content of the component (A) is 0.0005 to 5 w / v% based on the total amount of the aqueous ophthalmic composition.
Item 1-5. Item 5. The aqueous ophthalmic composition according to any one of Items 1-1 to 1-4, wherein the total content of component (B) is 0.001 to 5 w / v% based on the total amount of the aqueous ophthalmic composition.
Item 1-6. Item 6. The aqueous ophthalmic composition according to any one of Items 1-1 to 1-5, wherein the total content of the component (C) is 0.0001 to 5 w / v% based on the total amount of the aqueous ophthalmic composition.
Item 1-7. Item 7. The aqueous ophthalmic composition according to any one of Items 1-1 to 1-6, wherein the total content of vitamin A is 200 to 5000000 IU / 100 mL based on the total amount of the aqueous ophthalmic composition.
Item 1-8. Any one of Items 1-1 to 1-7, wherein the total content of component (B) is 0.0002 to 10,000 parts by weight with respect to 1 part by weight of the total content of component (A) An aqueous ophthalmic composition as described in 1. above.
Item 1-9. Any of Items 1-1 to 1-8, wherein the total content of component (C) is 0.00002 to 10,000 parts by weight with respect to 1 part by weight of the total content of component (A) An aqueous ophthalmic composition as described in 1. above.
Item 1-10. The aqueous ophthalmic composition according to any one of Items 1-1 to 1-9, further comprising a buffer.
Item 1-11. Item 11. The aqueous ophthalmic composition according to Item 1-10, wherein the buffer is a borate buffer.
Item 1-12. Item 11. The aqueous ophthalmic composition according to Item 1-10 or 1-11, wherein the total content of the buffer is 0.01 to 15 w / v% based on the total amount of the aqueous ophthalmic composition.
Item 1-13. Item 13. The aqueous ophthalmic composition according to any one of Items 1-1 to 1-12, which further contains a nonionic surfactant other than the component (A).
Item 1-14. The nonionic surfactant other than the component (A) is at least one selected from the group consisting of polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, and polyoxyethylene / polyoxypropylene / block copolymer. Item 14. The aqueous ophthalmic composition according to Item 1-13.
Item 1-15. The aqueous composition according to Item 1-13 or 1-14, wherein the total content of the nonionic surfactant other than the component (A) is 0.001 to 3 w / v% based on the total amount of the aqueous ophthalmic composition. Ophthalmic composition.
Item 1-16. Item 15. The aqueous ophthalmic composition according to any one of Items 1-1 to 1-15, which is filled in a polyethylene terephthalate container.
Item 1-17. Item 15. The aqueous ophthalmic composition according to any one of Items 1-1 to 1-16, which is filled in a container equipped with a polyethylene nozzle.
Item 1-18. The aqueous ophthalmic composition according to any one of Items 1-1 to 1-17, which is an eye drop.
Item 1-19. The aqueous ophthalmic composition according to any one of Items 1-1 to 1-17, which is an eye wash.
Item 1-20. The aqueous ophthalmic composition according to any one of Items 1-1 to 1-17, which is a contact lens mounting liquid.
Item 1-21. The aqueous ophthalmic composition according to any one of Items 1-1 to 1-17, which is a contact lens care agent.

Moreover, this invention provides the method of suppressing generation | occurrence | production of the precipitate in an aqueous ophthalmic composition of the aspect hung up below.
Item 2. An aqueous ophthalmic composition containing (A) polyoxyethylene castor oil and (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof is selected from the group consisting of (C) sesame oil and vitamin A The method to suppress generation | occurrence | production of the precipitate in this aqueous | water-based ophthalmic composition including mix | blending at least 1 type.
Item 3. An aqueous ophthalmic composition comprising (A) polyoxyethylene castor oil, (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, and (C) at least one selected from the group consisting of sesame oil and vitamin A A method for suppressing the generation of precipitates in the aqueous ophthalmic composition, comprising blending with the aqueous ophthalmic composition.

Furthermore, this invention provides the method of improving the photostability in the aqueous | water-based ophthalmic composition of the aspect hung up below.
Item 4. (A) The aqueous ophthalmic composition containing polyoxyethylene castor oil is selected from the group consisting of (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, and (C) sesame oil and vitamin A The method to improve the light stability in this aqueous | water-based ophthalmic composition including mix | blending at least 1 type.
Item 5. An aqueous ophthalmic composition comprising (A) polyoxyethylene castor oil, (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, and (C) at least one selected from the group consisting of sesame oil and vitamin A A method for improving light stability in the aqueous ophthalmic composition, comprising blending.

Furthermore, the present invention also provides the use of the following aspects.
Item 6. For production of an aqueous ophthalmic composition, (A) at least one selected from the group consisting of polyoxyethylene castor oil, (B) chondroitin sulfate and salts thereof, and (C) sesame oil and vitamin A At least one use selected from the group.
Item 7. Item 7. The use according to Item 6, wherein the aqueous ophthalmic composition is the composition according to any one of Items 1-1 to 1-21.

Furthermore, the present invention also provides the use of the embodiments listed below.
Item 8. As an aqueous ophthalmic composition, selected from the group consisting of (A) polyoxyethylene castor oil, (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, and (C) sesame oil and vitamin A Use of a composition comprising at least one of the above.
Item 9. The use according to Item 8, wherein the composition is the composition according to any one of Items 1-1 to 1-21.

Furthermore, this invention also provides the composition of the aspect hung up below.
Item 10. For use as an aqueous ophthalmic composition, (A) at least one selected from the group consisting of polyoxyethylene castor oil, (B) chondroitin sulfate and salts thereof, and (C) sesame oil and vitamin A A composition comprising at least one selected from the group consisting of:
Item 11. The composition according to Item 10, which is described in any one of Items 1-1 to 1-21 above.

Furthermore, this invention also provides the manufacturing method of the aqueous ophthalmic composition of the aspect hung up below.
Item 12. The carrier containing water is selected from the group consisting of (A) polyoxyethylene castor oil, (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, and (C) sesame oil and vitamin A. A method for producing an aqueous ophthalmic composition comprising adding at least one of the above.
Item 13. The method according to Item 12, wherein the aqueous ophthalmic composition is the composition according to any one of Items 1-1 to 1-21.

According to the present invention, the following various effects are exhibited.
(1) According to the present invention, it is possible to suppress the occurrence of precipitates that are likely to occur when the aqueous ophthalmic composition contains polyoxyethylene castor oil, at least one selected from the group consisting of chondroitin sulfate and salts thereof.
(2) According to the present invention, the photodegradation of polyoxyethylene castor oil contained in the aqueous ophthalmic composition can be suppressed.

  Therefore, the aqueous ophthalmic composition of the present invention can stably exhibit the excellent performance of the component (A), the component (B) and the component (C) for a long period of time without deteriorating safety and quality. it can.

A photograph showing a state after 7 days of storage for each aqueous ophthalmic composition used in Test Example 1.

  In the present specification, the unit “%” of content means “w / v%” and is synonymous with “g / 100 mL”.

  In the present specification, unless otherwise specified, the abbreviation “POE” means polyoxyethylene.

  In this specification, unless otherwise specified, the abbreviation “POP” means polyoxypropylene.

  In the present specification, unless otherwise specified, the contact lens is meant to include all types of contact lenses such as hard, oxygen-permeable hard, soft (including silicone hydrogel lenses), and color.

[1. Aqueous ophthalmic composition]
The aqueous ophthalmic composition of the present invention contains polyoxyethylene castor oil (component (A)). By using this together with at least one selected from the group consisting of chondroitin sulfate and salts thereof (component (B)) described later, and at least one selected from the group consisting of sesame oil and vitamin A (component (C)) The above-described excellent effects of the present invention are exhibited.

  Polyoxyethylene castor oil is a known compound obtained by addition polymerization of ethylene oxide to castor oil, and several types having different average added mole numbers of ethylene oxide are known. In the present invention, the average added mole number of ethylene oxide in the polyoxyethylene castor oil used as the component (A) is not particularly limited, but is, for example, about 2 to 70 moles. Specifically, polyoxyethylene castor oil 3 having an average addition mole number of ethylene oxide of 3, polyoxyethylene castor oil 4 having an average addition mole number of ethylene oxide of 4, and an average addition mole number of ethylene oxide of 6 Polyoxyethylene castor oil 6, polyoxyethylene castor oil 7 with an average addition mole number of ethylene oxide of 7, polyoxyethylene castor oil 10 with an average addition mole number of ethylene oxide of 10, an average addition of ethylene oxide Polyoxyethylene castor oil 13.5 having a mole number of 13.5, polyoxyethylene castor oil 17 having an average addition mole number of ethylene oxide of 17, polyoxyethylene castor oil having an average addition mole number of ethylene oxide of 20 Oil 20, polyoxyethylene castor oil 25 having an average added mole number of ethylene oxide of 25, ethylene oxide Polyoxyethylene castor oil 30 having an average addition mole number of 30, polyoxyethylene castor oil 35 having an average addition mole number of ethylene oxide of 35, polyoxyethylene castor oil 40 having an average addition mole number of ethylene oxide of 40 Polyoxyethylene castor oil 50 having an average addition mole number of ethylene oxide of 50, polyoxyethylene castor oil 60 having an average addition mole number of ethylene oxide of 60, and polyoxyethylene having an average addition mole number of ethylene oxide of 70 Ethylene castor oil 70 etc. are mentioned.

  Among these polyoxyethylene castor oils, as an example of a component that can satisfactorily exert the effects of the present invention, the average added mole number of ethylene oxide is 2 to 35 mol, preferably 2 to 30, more preferably 2 to 20 Particularly preferred are 2 to 12 polyoxyethylene castor oils.

  In the present invention, these polyoxyethylene castor oils may be used alone or in any combination of two or more. In addition, the polyoxyethylene castor oil used by this invention is a compound different from the polyoxyethylene hydrogenated castor oil obtained by addition-polymerizing ethylene oxide to hydrogenated castor oil, and is distinguished from this.

  The content of the component (A) in the aqueous ophthalmic composition of the present invention is not particularly limited, and the type and content of the component (A), the components (B) and (C) to be used together, the aqueous ophthalmic composition It is set as appropriate according to the use of the product, the formulation form, the method of use and the like. For example, based on the total amount of the aqueous ophthalmic composition, the total content of the component (A) is 0.0005 to 5 w / v%, preferably 0.001 to 4 w / v%, more preferably 0.002 to 3 w / v. It is v%, more preferably 0.005 to 2 w / v%, particularly preferably 0.01 to 1 w / v%.

  The content of the component (A) is preferable from the viewpoint of further enhancing the action of suppressing precipitates and the action of improving light stability in the aqueous ophthalmic composition.

  The aqueous ophthalmic composition of the present invention needs to contain at least one (component (B)) selected from the group consisting of chondroitin sulfate and a salt thereof in addition to the component (A) described above. Chondroitin sulfate and salts thereof are known compounds, and may be produced by a known method or may be obtained as a commercial product.

  The chondroitin sulfate used in the present invention is not particularly limited in its origin as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable. Etc.) and the like. The molecular weight of chondroitin sulfate used in the present invention is not particularly limited. For example, the viscosity average molecular weight is 10,000 to 100,000, preferably 50,000 to 70,000, and more preferably 10,000 to 50,000. It is. Here, the viscosity average molecular weight is determined according to the sixteenth revised Japanese Pharmacopoeia General Test Method Viscosity Measurement Method First Method: Intrinsic Viscosity η according to Capillary Viscometer Method (Measurement Conditions: Solution 0.2 mol / L NaCl, The temperature is 25.0 ± 0 ° C., Ubbelohde viscometer) and the obtained intrinsic viscosity η is calculated from the following formula I.

[η] = 5.8 × 10 ⁻⁴ M ^0.74 (Formula I)
(M is the viscosity average molecular weight.)
The salt of chondroitin sulfate used in the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. As a salt of chondroitin sulfate, specifically, a salt with an organic base (for example, a salt with an organic amine such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.), an inorganic base And various salts such as ammonium salts (for example, salts with alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), metals such as aluminum, etc.). Among these salts, a salt of chondroitin sulfate with an inorganic base is preferable, an alkali metal salt is more preferable, and sodium chondroitin sulfate is more preferable. These chondroitin sulfate salts may be used singly or in combination of two or more.

  The content of the component (B) in the aqueous ophthalmic composition of the present invention is not particularly limited.The type of the component (B), the types of the components (A) and (C) to be used together, the use of the aqueous ophthalmic composition, It is appropriately set according to the formulation form, usage method and the like. For example, based on the total amount of the aqueous ophthalmic composition of the present invention, the total content of the component (B) is 0.001 to 5 w / v%, preferably 0.002 to 2 w / v%, more preferably 0.005. ˜1 w / v%, particularly preferably 0.01 to 0.5 w / v%.

  The content of the component (B) is suitable from the viewpoint of further enhancing the effects of the present invention.

  Further, the content ratio of the component (B) to the component (A) in the aqueous ophthalmic composition of the present invention is not particularly limited, the types of the components (A) and (B), the use of the aqueous ophthalmic composition, and the preparation It is appropriately set according to the form, usage method, and the like. For example, with respect to 1 part by weight of the total content of the component (A) contained in the aqueous ophthalmic composition of the present invention, the total content of the component (B) is 0.0002 to 10,000 parts by weight, preferably 0.001. -1000 parts by weight, more preferably 0.005-200 parts by weight, particularly preferably 0.01-50 parts by weight.

  The content ratio of the component (B) to the component (A) is preferable from the viewpoint of further enhancing the effect of the present invention.

  The aqueous ophthalmic composition of the present invention needs to contain at least one selected from the group consisting of sesame oil and vitamin A (component (C)) in addition to the components (A) and (B) described above. is there.

  Sesame oil refers to a vegetable oil obtained from the seed of a plant belonging to the sesame family Sesame (Sesamumindicum Linne (Pedaliaceae), etc.).

  The sesame oil used in the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable, and the seed is obtained using a known exploitation method or a known purification method. Those obtained from the above and commercially available ones can be used.

  Vitamin A is a kind of fat-soluble vitamin and is an essential nutrient for the human body. Vitamin A is a substance having vitamin A activity, and both natural and synthetic products can be used.

  Vitamin A used in the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable, and specifically, retinol, retinal, retinoic acid, these Derivatives, salts and the like.

  Derivative forms of vitamin A include, for example, retinol palmitate, retinol acetate, retinol butyrate, retinol propionate, retinol octylate, retinol laurate, retinol oleate, retinol linolenate, retinal, retinoic acid, methyl retinoic acid, retinoin Examples include ethyl acid, retinoic acid retinol, δ-tocopheryl retinoate, α-tocopheryl retinoate, β-tocopheryl retinoate and the like.

  The vitamin A in the salt form is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and specifically, an organic acid salt [for example, monocarboxylic acid] Acid salt (acetate, trifluoroacetate, butyrate, palmitate, stearate, etc.), polyvalent carboxylate (fumarate, maleate, succinate, malonate, etc.), oxycarboxyl Acid salt (lactate, tartrate, citrate, etc.), organic sulfonate (methanesulfonate, toluenesulfonate, tosylate, etc.)], inorganic acid salt (eg, hydrochloride, sulfate, Nitrates, hydrobromides, phosphates, etc.), salts with organic bases (eg methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.) Etc.), salts with inorganic bases [for example, ammonium salts; alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), salts with metals such as aluminum, etc.] and the like.

  Vitamin A may be either isolated from natural products such as animal materials or chemically synthesized. Vitamin A can also be used as vitamin A oil in the form of vitamin A dissolved in oil. Vitamin A oil may be natural oil extracted and purified from animals, or may be vitamin A dissolved in vegetable oil or the like.

  These vitamin As may be used alone or in any combination of two or more. Among these vitamin A, from the viewpoint of further suppressing the generation of precipitates and further enhancing the photostability, preferably retinol, its derivatives, and salts thereof, more preferably retinol acetate and palmitic acid. Examples include acid retinol, particularly preferably retinol palmitate.

  The content of the component (C) in the aqueous ophthalmic composition of the present invention is not particularly limited.The type of the component (C), the types of the component (A) and the component (B) to be used together, the use of the aqueous ophthalmic composition, It is appropriately set according to the formulation form, usage method and the like. For example, based on the total amount of the aqueous ophthalmic composition of the present invention, the total content of component (C) is 0.0001 to 5 w / v%, preferably 0.0005 to 1 w / v%, more preferably 0.00. 001-0.5 w / v%, particularly preferably 0.002-0. 2 w / v%.

  As can generally be understood by those skilled in the art, IU is known as an international unit for the amount of vitamin A. For example, in the case of retinol, 1 IU corresponds to about 0.30 μg of retinol, in the case of retinol acetate, 1 IU = corresponds to about 0.34 μg of retinol acetate, and in the case of retinol palmitate, 1 IU = about 0. It is well known to correspond to 55 μg retinol palmitate.

  When the content of vitamin A is represented by IU, for example, based on the total amount of the aqueous ophthalmic composition of the present invention, the total content of vitamin A is 200 to 5000000 IU / 100 mL, preferably 500 to 1000000 IU / 100 mL, More preferably, it is 1000-500000 IU / 100 mL, Most preferably, it is 2000-100000 IU / 100 mL.

  The content of the component (C) is preferable from the viewpoint of further enhancing the effects of the present invention.

  Further, the content ratio of the component (C) to the component (A) in the aqueous ophthalmic composition of the present invention is not particularly limited, the types of the components (A) and (C), the use of the aqueous ophthalmic composition, and the preparation It is appropriately set according to the form, usage method, and the like. For example, with respect to 100 parts by weight of the total content of component (A) contained in the aqueous ophthalmic composition of the present invention, the total content of component (C) is 0.00002 to 10,000 parts by weight, preferably 0.0001. It is -2000 weight part, More preferably, it is 0.0005-500 weight part, More preferably, it is 0.001-100 weight part, Most preferably, it is 0.002-20 weight part.

  The content ratio of the component (C) to the component (A) is preferable from the viewpoint of further enhancing the effect of the present invention.

  In the aqueous ophthalmic composition of the present invention, as described later, various pharmacologically active ingredients, physiologically active ingredients and the like can be blended according to the purpose of use, and various additives can be blended. . In this case, in order to improve the solubility of physiologically active ingredients and additives, in addition to the component (A), other surfactants can be further blended as a solubilizing agent.

  The surfactant other than the component (A) that can be blended in the aqueous ophthalmic composition of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. However, any of nonionic surfactants, amphoteric surfactants, anionic surfactants, and cationic surfactants may be used.

  Specific examples of the nonionic surfactant other than the component (A) that can be blended in the aqueous ophthalmic composition of the present invention include monolauric acid POE (20) sorbitan (polysorbate 20) and monopalmitic acid POE (20). POE sorbitan fatty acid esters such as sorbitan (polysorbate 40), monostearic acid POE (20) sorbitan (polysorbate 60), tristearic acid POE (20) sorbitan (polysorbate 65), monooleic acid POE (20) sorbitan (polysorbate 80) ; POE (40) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 40), POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60), etc .; POE (9) POE such as lauryl ether; POE-POP alkyl ethers such as POE (20) POP (4) cetyl ether; POE (196) POP (67) glycol (poloxamer 407, Pluronic F127) , POE (200) POP (70) Polyoxyethylene-polyoxypropylene block copolymers such as glycol. In the compounds exemplified above, the numbers in parentheses indicate the number of added moles.

  Specific examples of the amphoteric surfactant that can be incorporated into the aqueous ophthalmic composition of the present invention include alkyldiaminoethylglycine or a salt thereof (for example, hydrochloride).

  Specific examples of the cationic surfactant that can be blended in the aqueous ophthalmic composition of the present invention include benzalkonium chloride and benzethonium chloride.

  Specific examples of the anionic surfactant that can be incorporated into the aqueous ophthalmic composition of the present invention include alkylbenzene sulfonate, alkyl sulfate, polyoxyethylene alkyl sulfate, and aliphatic α-sulfomethyl ester. And α-olefin sulfonic acid.

  The surfactant other than the component (A) that can be blended in the aqueous ophthalmic composition of the present invention is preferably a nonionic surfactant, more preferably POE sorbitan fatty acid ester, POE hydrogenated castor oil, POE POP block copolymers, particularly preferably polysorbate 80, polyoxyethylene hydrogenated castor oil 60, and poloxamer 407.

  In the aqueous ophthalmic composition of the present invention, surfactants other than the component (A) may be used singly or in combination of two or more.

  When a surfactant other than the component (A) is blended in the aqueous ophthalmic composition of the present invention, the content thereof is the type of the surfactant, the type and content of other blended components, the aqueous ophthalmic composition. Is appropriately set according to the use, formulation form, method of use and the like. For example, based on the total amount of the aqueous ophthalmic composition of the present invention, the total content of surfactants other than the component (A) is 0.001 to 3 w / v%, preferably 0.005 to 2 w / v%, More preferably, it is 0.01-1 w / v%, Most preferably, it is 0.05-1 w / v%.

  The aqueous ophthalmic composition of the present invention can further contain a buffer. Thereby, pH of the aqueous ophthalmic composition of this invention can be adjusted. The buffer that can be incorporated into the aqueous ophthalmic composition 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, aspartic acid, aspartate, epsilon-aminocaproic acid, etc. It is done. These buffering agents may be used alone or in any combination of two or more. Examples of the boric acid buffer include boric acid or boric acid salts such as alkali metal borate and alkaline earth metal borate. Examples of the phosphate buffer include phosphoric acid or phosphates such as alkali metal phosphates and alkaline earth metal phosphates. Examples of the carbonate buffer include carbonates or carbonates such as alkali metal carbonates and alkaline earth metal carbonates. Examples of the citrate buffer include citric acid, 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 a more specific example, boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.); as a phosphate buffer, phosphoric acid or a salt thereof Salt (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.); Or a salt thereof (sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc.); citric acid or a salt thereof (sodium citrate, potassium citrate, citric acid, etc.) Calcium acetate, sodium dihydrogen citrate, disodium citrate, etc.); with acetate buffer Examples thereof include acetic acid or a salt thereof (ammonium acetate, potassium acetate, calcium acetate, sodium acetate, etc.); aspartic acid or a salt thereof (sodium aspartate, magnesium aspartate, potassium aspartate, etc.). Among these buffering agents, boric acid buffering agents (particularly a combination of boric acid and borax) and phosphoric acid buffering agents (particularly a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate) are preferable.

  When a buffering agent is blended in the aqueous ophthalmic composition of the present invention, the content thereof includes the type of the buffering agent, the type and content of other blending components, the use of the aqueous ophthalmic composition, the formulation form, the method of use, etc. It is set appropriately according to For example, based on the total amount of the aqueous ophthalmic composition of the present invention, the total content of the buffer is 0.01 to 15 w / v%, preferably 0.05 to 10 w / v%, more preferably 0.1. -7.5 w / v%, particularly preferably 0.5-5 w / v%.

  The aqueous ophthalmic composition of the present invention may further contain an isotonic agent. The isotonic agent that can be incorporated into the aqueous ophthalmic composition of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specific examples of such isotonic agents include, for example, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium hydrogen sulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride Potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol, polyethylene glycol, glucose, mannitol, sorbitol and the like. Among these tonicity agents, glycerin, propylene glycol, glucose, sodium chloride, potassium chloride, calcium chloride, and magnesium chloride are preferable. These isotonic agents may be used alone or in any combination of two or more.

  When an isotonic agent is blended in the aqueous ophthalmic composition of the present invention, the content thereof includes the type of tonicity agent, the type and content of other compounding ingredients, the use of the aqueous ophthalmic composition, and the formulation form. It is set as appropriate according to the method of use. For example, based on the total amount of the aqueous ophthalmic composition of the present invention, the total content of the tonicity agent is 0.005 to 10 w / v%, preferably 0.01 to 5 w / v%, more preferably 0. 0.05 to 3 w / v%.

  The pH of the aqueous ophthalmic composition 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 aqueous ophthalmic composition of the present invention is 4.0 to 9.5, preferably 5.0 to 9.0, and more preferably 5.5 to 8.5.

  In addition, the osmotic pressure of the aqueous ophthalmic composition 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 aqueous ophthalmic composition of the present invention, 0.5 to 5.0, preferably 0.6 to 3.0, more preferably 0.7 to 2.0, and particularly preferably 0.9 to 1.55. The adjustment of the osmotic pressure can be performed by a method known in the art using an inorganic salt, a polyhydric alcohol, a sugar alcohol, a sugar or the like. The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (0.9 w / v% sodium chloride aqueous solution) based on the 16th revised Japanese Pharmacopeia. Measured with reference to the method (freezing point depression method). In addition, about the standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution), after drying sodium chloride (Japanese Pharmacopoeia standard reagent) at 500-650 degreeC for 40-50 minutes, it is a desiccator (silica gel). It is allowed to cool, and 0.900 g is accurately weighed and dissolved in purified water to prepare exactly 100 mL, or a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution) may be used. .

  The viscosity of the aqueous ophthalmic composition of the present invention is not particularly limited as long as it is within a range acceptable for a living body. For example, the viscosity at 25 ° C. measured with a rotational viscometer (RE550 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1 ° 34 ′ × 24) is 0.01 to 1000 mPa · s, preferably 0.05 to 100 mPa · s. s, more preferably 0.1 to 10 mPa · s.

  The aqueous ophthalmic composition of the present invention may contain an appropriate amount of various pharmacologically active ingredients and / or physiologically active ingredients in addition to the above ingredients, as long as the effects of the present invention are exhibited. Such components are not particularly limited, and specific examples of components used in ophthalmic drugs include the following components.

  Antihistamine or antiallergic agent: for example, iproheptin, diphenhydramine hydrochloride, chlorpheniramine maleate, ketotifen fumarate, potassium pemirolast, sodium cromoglycate, and the like.

  Decongestant: For example, tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline sulfate epinephrine hydrochloride, ephedrine hydrochloride, methylephedrine hydrochloride, and the like.

  Eye muscle modulating agent: for example, cholinesterase inhibitor having an active center similar to acetylcholine, specifically, neostigmine methyl sulfate, tropicamide, atropine sulfate helenien.

  Vitamins: For example, flavin adenine dinucleotide sodium, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, tocopherol acetate, etc.

  Amino acids: for example, potassium aspartate, magnesium aspartate, aminoethylsulfonic acid, epsilon-aminocaproic acid and the like.

  Anti-inflammatory agents: for example, zinc sulfate, zinc lactate, bromfenac sodium, dipotassium glycyrrhizinate, pranoprofen, allantoin, azulene, sodium azulenesulfonate, guaiazulene, berberine chloride, berberine sulfate, lysozyme chloride, licorice, etc.

  Other: For example, sodium hyaluronate, sulfamethoxazole, sulfamethoxazole sodium and the like.

  Further, in the aqueous ophthalmic composition of the present invention, various additives are appropriately selected according to conventional methods depending on the use, formulation form, etc., as long as the effects of the invention are exerted, and one type or An appropriate amount may be added in combination. Typical additives include the following additives.

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

  Sugar: For example, cyclodextrin and the like.

  Sugar alcohol: For example, xylitol, sorbitol, mannitol and the like. These may be d-form, l-form or dl-form.

  Preservatives, bactericides or antibacterials: for example, cetylpyridinium, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, polyhexanide hydrochloride, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, chlorhexidine gluconate, chlorobutanol , Sorbic acid, potassium sorbate, sodium dehydroacetate, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, glowul (trade name, Rhodia) etc.

  Thickening agent or thickener: gum arabic powder, sodium alginate, propylene glycol alginate, sorbitol, dextran 70, tragacanth powder, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, carboxyvinyl polymer, polyvinyl alcohol, polyvinylpyrrolidone , Macrogol 4000 etc.

  Oils: castor oil, etc.

  In the aqueous ophthalmic composition of the present invention, a desired amount of the above-mentioned component (A), component (B) and component (C), and other compounding components as required, are added to the carrier so as to have a desired concentration. It is prepared by. For example, in the case of eye drops, contact lens mounting solution, eye wash or contact lens care agent, the above components are dissolved or suspended in purified water, adjusted to a predetermined pH and osmotic pressure, and sterilized by filtration sterilization, etc. Can be prepared. Regarding the dissolution of the above component (A), component (B), and component (C) and other highly hydrophobic components, after stirring together with a component having a solubilizing action such as a surfactant in advance. Further, purified water may be added and dissolved or suspended.

  Therefore, from another viewpoint, the present invention provides a carrier containing water with (A) polyoxyethylene castor oil, (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, and (C) sesame oil and The present invention provides a method for producing an aqueous ophthalmic composition, which comprises adding at least one selected from the group consisting of vitamin A.

  In the present invention, the aqueous ophthalmic composition means an ophthalmic composition having a water content of 85 w / v% or more based on the total amount of the aqueous ophthalmic composition. The water content in the aqueous ophthalmic composition is preferably 90 w / v% or more, more preferably 92 w / v% or more, still more preferably 94 w / v% or more, and particularly preferably 96 w / v% or more. As water used in the aqueous ophthalmic composition of the present invention, water that is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable may be used, and as such water, specifically, Examples include distilled water, ordinary water, purified water, sterilized purified water, water for injection, distilled water for injection, and the like. In addition, the dosage form of the aqueous ophthalmic composition in the present invention is not particularly limited as long as it can be used in the ophthalmic field, but a liquid form is preferable. These definitions are based on the 16th revised Japanese Pharmacopoeia.

  The aqueous ophthalmic composition of the present invention can be used as a pharmaceutical preparation, quasi-drug, and the like, and includes eye drops [however, eye drops include eye drops that can be applied while wearing contact lenses], artificial tears, and eyewashes. [However, eyewash contains eyewash that can be washed while wearing contact lens], contact lens composition [contact lens mounting solution, contact lens care composition (contact lens disinfectant, contact lens preservative] , Contact lens cleaning agents, contact lens cleaning preservatives, etc.]. Preferable examples of the aqueous ophthalmic composition of the present invention include eye drops, artificial tears, eye wash, contact lens mounting liquid, and particularly preferable examples include eye drops and artificial tears. In addition, when using as a composition for contact lenses, it is applicable to all contact lenses including a hard contact lens and a soft contact lens.

  As a container for containing the aqueous ophthalmic composition of the present invention, a container usually used as a container for containing the aqueous ophthalmic composition can be used, and it may be made of glass or plastic. When the plastic container is used as the container for storing the aqueous ophthalmic composition of the present invention, the constituent material of the plastic container is not particularly limited. For example, polyethylene naphthalate, polyarylate, polyethylene terephthalate, polypropylene, polyethylene, Any one of polyimides, a copolymer thereof, or a mixture of two or more types can be given. 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. In the present invention, for example, a container made of polyethylene terephthalate means that the polyethylene terephthalate is 50 w / w% or more based on the weight of the entire material constituting the container.

  In addition, the structure, constituent materials, and the like of the peripheral portion of the container inlet such as a nozzle provided in the container for storing the aqueous ophthalmic composition of the present invention are not particularly limited. The structure around the container inlet such as a nozzle may be a structure generally employed as a spout (for example, a nozzle) of a container for an ophthalmic composition (for example, an eye drop container), and is integrated with the container body. It may be molded or may be molded separately from the container body. As the constituent material of the spout peripheral portion or the spout (for example, nozzle), for example, the same material as that of the plastic container is exemplified.

  In another aspect, the present invention provides at least one selected from the group consisting of (A) polyoxyethylene castor oil, (B) chondroitin sulfate and salts thereof for the production of an aqueous ophthalmic composition, and ( C) Also provides at least one use selected from the group consisting of sesame oil and vitamin A.

  Further, the present invention provides, from another viewpoint, as an aqueous ophthalmic composition, (A) at least one selected from the group consisting of polyoxyethylene castor oil, (B) chondroitin sulfate and salts thereof, and (C) sesame oil. And the use of a composition comprising at least one selected from the group consisting of vitamin A.

  Furthermore, the present invention, from another viewpoint, for use as an aqueous ophthalmic composition, (A) at least one selected from the group consisting of polyoxyethylene castor oil, (B) chondroitin sulfate and salts thereof, and (C) A composition comprising at least one selected from the group consisting of sesame oil and vitamin A is provided.

[2. Method for suppressing generation of precipitates]
As described above, in the aqueous ophthalmic composition, (A) at least one selected from the group consisting of polyoxyethylene castor oil, (B) chondroitin sulfate and salts thereof, and (C) from the group consisting of sesame oil and vitamin A By blending at least one selected, it is possible to suppress the occurrence of precipitates that are likely to occur in the aqueous ophthalmic composition containing the components (A) and (B).

  Accordingly, the present invention provides an aqueous ophthalmic composition containing (A) polyoxyethylene castor oil, and (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, from (C) sesame oil and vitamin A. The present invention provides a method for suppressing the generation of precipitates in the aqueous ophthalmic composition, which comprises blending at least one selected from the group consisting of:

  Further, the present invention provides (A) at least one selected from the group consisting of polyoxyethylene castor oil, (B) chondroitin sulfate and salts thereof, and (C) at least one selected from the group consisting of sesame oil and vitamin A. The method of suppressing generation | occurrence | production of the deposit in this aqueous ophthalmic composition including mix | blending with an aqueous ophthalmic composition is provided.

  In the above-described method, as long as the component (A), the component (B), and the component (C) coexist in the aqueous ophthalmic composition, the order of addition thereof is not particularly limited. In addition, for the component (A), the component (B) and the component (C), the type and content of each component, the type and content of other components, the formulation form of the composition, etc. In “1. Aqueous ophthalmic composition”.

  In addition, in this specification, it can be determined by the method as described in the below-mentioned Example whether generation | occurrence | production of the precipitate in an aqueous ophthalmic composition is suppressed.

[3. Light stabilization method]
As described above, the aqueous ophthalmic composition contains (A) polyoxyethylene castor oil, (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, and (C) a group consisting of sesame oil and vitamin A. By blending at least one selected from the above, photodegradation of polyoxyethylene castor oil contained in the aqueous ophthalmic composition can be suppressed.

  Accordingly, the present invention provides an aqueous ophthalmic composition containing (A) polyoxyethylene castor oil, (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, and (C) sesame oil and vitamin A. The present invention provides a method for improving the light stability in the aqueous ophthalmic composition, which comprises blending at least one selected from the group consisting of:

  Further, the present invention provides an aqueous ophthalmic composition comprising (A) polyoxyethylene castor oil, (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, and (C) a group consisting of sesame oil and vitamin A. The present invention provides a method for improving light stability in the aqueous ophthalmic composition, which comprises blending at least one selected from the above.

  In the above-described method, as long as the component (A), the component (B), and the component (C) coexist in the aqueous ophthalmic composition, the order of addition thereof is not particularly limited. In addition, for the component (A), the component (B) and the component (C), the type and content of each component, the type and content of other components, the formulation form of the composition, etc. In “1. Aqueous ophthalmic composition”.

  In addition, in this specification, it can be determined by the method as described in the below-mentioned Example whether the light stability in the aqueous ophthalmic composition is improved.

Hereinafter, the present invention will be described in detail with reference to Examples and Test Examples, but the present invention is not limited to these Examples and the like.

[ Test Example 1 Test for Precipitation Suppression (1) ]
Aqueous ophthalmic compositions having the compositions shown in Tables 1 and 2 below were prepared by a conventional method, and the occurrence of precipitates was evaluated. As the polyethylene castor oil 10, one having an average added mole number of ethylene oxide that conforms to the standard of polyoxyethylene castor oil of the pharmaceutical additive standard 2003 was used. As the chondroitin sulfate sodium salt, one conforming to the standard of the pharmaceutical additive standard 2003 was used. As sesame oil, a product made by SIGMA is used, and as vitamin A oil, it contains 55% by weight of retinol palmitate, which is vitamin A, and 45% by weight of sunflower oil, and is an international unit for the amount of vitamin A. In terms of IU, 1 million IU / g was used.

  Next, 10 mL of each prepared aqueous ophthalmic composition was filled into a 10 mL capacity glass headspace vial and stored in a thermostat at 70 ° C. under light shielding. After storage for 7 days, the presence or absence of precipitates in each aqueous ophthalmic composition was confirmed, and when there were precipitates, the turbidity by turbidity measurement was evaluated. The turbidity was measured using a turbidimeter MICROPLATE READER SH-9000Lab (CORONA), and purified water was used as a blank.

  Based on the white turbidity of the aqueous ophthalmic compositions of each Reference Example, Comparative Example, and Example, measured by the above method, the precipitation inhibition rate was calculated based on the following formula. The calculation results are shown in Tables 1 and 2 together. Moreover, the photograph which shows the state of each aqueous ophthalmic composition of the comparative example and Example 7 days after a preservation | save is shown in FIG.

  Precipitation inhibition rate (%) = (turbidity of Comparative Example 1−turbidity of each Example) / (turbidity of Comparative Example 1) × 100

  As shown in Tables 1 and 2, and FIG. 1, precipitates were observed in the aqueous ophthalmic composition containing polyoxyethylene castor oil 10 and sodium chondroitin sulfate (Comparative Example 1). On the other hand, in the aqueous ophthalmic composition containing sesame oil or vitamin A oil together with polyoxyethylene castor oil 10 and sodium chondroitin sulfate, the turbidity was remarkably reduced and the occurrence of precipitation was suppressed (Example 1). 2).

[ Test Example 2 Test (2) concerning precipitation suppression ]
An aqueous ophthalmic composition having the composition shown in Table 3 below was prepared by a conventional method, and the presence or absence of precipitates and the precipitation inhibition rate were evaluated. The same polyoxyethylene castor oil 10 and sodium chondroitin sulfate as in Test Example 1 were used. As vitamin E, DL-α-tocopherol acetate conforming to the standard of the 16th revised Japanese Pharmacopeia was used.

  Using these aqueous ophthalmic compositions, the precipitation inhibition rate was calculated based on the following formula in the same manner as in Test Example 1. The calculation results are also shown in Table 3.

  Precipitation inhibition rate (%) = (turbidity of comparative example 1−turbidity of comparative example 2) / (turbidity of comparative example 1) × 100

  As shown in Table 3, precipitates were observed in the aqueous ophthalmic composition containing polyoxyethylene castor oil 10 and sodium chondroitin sulfate (Comparative Example 1). On the other hand, in the aqueous ophthalmic composition containing vitamin E together with polyoxyethylene castor oil 10 and sodium chondroitin sulfate, the turbidity slightly increased due to the increase in precipitates (Comparative Example 2).

[ Test Example 3 Photostability Test ]
An aqueous ophthalmic composition having the composition shown in Table 4 below was prepared by a conventional method, and the photostability was evaluated. The same polyoxyethylene castor oil 10, sesame oil, and sodium chondroitin sulfate as in Test Example 1 were used.

  Next, 5 mL each of the prepared aqueous ophthalmic composition was filled into a 10 mL glass screw vial. Using an optical stability tester (“Light-Tron LT-120 D3CJ”, manufactured by Nagano Science Co., Ltd.) The composition was exposed to light having an integrated irradiation amount of 600,000 lx · hr. After exposure, the content of polyoxyethylene castor oil 10 in the aqueous ophthalmic composition was quantified using HPLC, and the residual rate was calculated according to the following formula.

Residual rate (%) = (polyoxyethylene castor oil 10 content after light irradiation) / (polyoxyethylene castor oil 10 content before light irradiation) × 100
Furthermore, the light stability improvement rate (%) was calculated using the following equation. The calculation results are also shown in Table 4.

  Light stability improvement rate (%) = {(residual rate of Example 3 / residual rate of Comparative Example 3) −1} × 100

  As shown in Table 4, for the aqueous ophthalmic composition containing polyoxyethylene castor oil 10 (Comparative Example 3), in the aqueous ophthalmic composition containing sesame oil and sodium chondroitin sulfate together with polyoxyethylene castor oil 10, It was confirmed that the residual rate of the polyoxyethylene castor oil 10 was significantly improved and the light stability improvement rate of the polyoxyethylene castor oil 10 was increased (Example 3).

  Although not shown in the table, the aqueous ophthalmic composition containing sesame oil and sodium chondroitin sulfate together with the polyoxyethylene castor oil 35 when compared with the aqueous ophthalmic composition containing the polyoxyethylene castor oil 35. Then, it was confirmed that the residual rate of the polyoxyethylene castor oil 35 was remarkably improved, and the light stability improvement rate of the polyoxyethylene castor oil 35 was increased.

Formulation Examples In the formulations described in Tables 5 to 8, eye drops (Formulation Examples 1-8 and 12-19), eye wash (Formulation Examples 9, 10, 20, and 21), and eye drops for soft contact lenses (formulations) Examples 11, 22) are prepared. The retinol palmitate is vitamin A palmitate (900,000 to 1.05 million IU / g) manufactured by Wako Pure Chemical Industries, Ltd.

Claims (6)

  An aqueous ophthalmic composition containing (A) polyoxyethylene castor oil, (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, and (C) at least one selected from the group consisting of sesame oil and vitamin A object.   The aqueous ophthalmic composition according to claim 1, further comprising a nonionic surfactant other than the component (A). The total content of the component (C) is 0.0001 to 5 w / v% and the total content of vitamin A is 200 to 5000000 IU / 100 mL based on the total amount of the aqueous ophthalmic composition. The aqueous ophthalmic composition according to 2. The aqueous ophthalmic composition according to any one of claims 1 to 3, wherein the total content of the component (B) is 0.0002 to 10,000 parts by weight with respect to 1 part by weight of the total content of the component (A). object. The aqueous ophthalmic composition according to any one of claims 1 to 4, which is contained in a plastic container. An aqueous ophthalmic composition comprising (A) polyoxyethylene castor oil, (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, and (C) at least one selected from the group consisting of sesame oil and vitamin A A method of improving the light stability in the aqueous ophthalmic composition and / or suppressing the generation of precipitates in the aqueous ophthalmic composition , comprising blending.