WO2004082673A1

WO2004082673A1 - Liquid ophthalmic composition

Info

Publication number: WO2004082673A1
Application number: PCT/JP2004/002782
Authority: WO
Inventors: Sadayasu Tanikawa; Akira Tsuzuki
Original assignee: Menicon Co. Ltd.
Priority date: 2003-03-20
Filing date: 2004-03-04
Publication date: 2004-09-30

Abstract

It is intended to provide a liquid ophthalmic composition which sustains a sufficient safety for the eye, prevents contact lenses from swelling or shrinkage to thereby cause no change in size, achieves an excellent compatibility with lenses, relieves unpleasantness, dryness, etc. in the eye in wearing contact lenses or VDT operations, and can advantageously maintain the relieving effect. It is also intended to effectively improve the bactericidal effect of a bactericide contained in the above-described liquid ophthalmic composition in the case of using the liquid ophthalmic composition as a liquid composition containing a bactericide for contact lenses, more specifically speaking, using it as a liquid bactericide or MPS for contact lenses. The liquid ophthalmic composition is prepared by adding at least one specific aminosugar derivative into an aqueous medium.

Description

Description Ophthalmic solution composition Technical field

The present invention relates to an ophthalmic solution composition,

Exhibits excellent lens compatibility without adverse effects such as changes, and reduces discomfort and dryness of the eyes caused by wearing contact lenses and VDT (Visual Display Terminal) work. The present invention relates to an ophthalmic solution composition capable of advantageously maintaining its effects, and more particularly to a contact lens solution composition and an ophthalmic composition. Background technology

Conventionally, contact lenses have been categorized into non-hydrated contact lenses and hydrated contact lenses, or hard contact lenses and soft contact lenses. Therefore, in any of those contact lenses, the wearing of proteins, lipids, and other stains derived from tears may adhere to the contact lens depending on the wearing thereof, and furthermore, the tears of such lenses Continue to use such contact lenses safely and comfortably every day since the liquid stains may cause deterioration of wearing feeling, deterioration of visual acuity, and eye disorders such as conjunctival congestion. Therefore, it is indispensable to carry out cleaning treatment on contact lenses.

In addition to such cleaning treatment, in order to prevent contamination of the contact lens during storage by microorganisms such as bacteria and vitreous bacteria, the contact lens removed from the eyes is disinfected. It is necessary to store contact lenses in a suitable solution until the next use. And cleaning, disinfecting, and preserving such contact lenses is important for safe use of contact lenses. This is an indispensable process.

For cleaning, disinfection, and preservation of these contact lenses, one or more liquids such as a sterilizing solution for the contact lenses, a cleaning solution, a preservative solution, a rinsing solution, etc., and a plurality of types of care are performed. Can wash, preserving solution, washing and preserving. Various types of versatile liquids (multi-purpose solution:] ^ P S) such as rinsing liquid and sterilizing liquid have been marketed overseas and in Japan.

In such a contact lens solution, various compounds have been conventionally studied as a bactericide component to be added thereto. However, in order to obtain practically high bactericidal properties using these compounds, all of the compounds had to be used in high concentrations. For example, fungicide components include biguanide compounds represented by polyhexamethylene biguanide (P HMB), which is an organic nitrogen-based fungicide, and quaternary ammonium compounds represented by benzalkonium chloride and polyquatanium. It is used over a wide range because it has particularly useful germicidal properties compared to other germicide components. Otherwise, it is known that sufficient bactericidal and antiseptic effects cannot be obtained.

For this reason, in order to satisfy practical requirements from the viewpoint of sterilization or preservation, it is necessary to increase the use amount of such a bactericide. However, it becomes easier to adsorb to contact lenses, especially soft contact lenses, and as a result, the wettability of the lens surface is reduced, the physical properties and shape of the lens are changed, and in some cases, it may be applied to the mucous membrane of the eyes when worn Stimulation to the eye may cause eye damage, which raises safety issues. Therefore, at present, studies are being conducted on the composition of fungicides so as to obtain higher fungicidal efficacy with a lower content.

On the other hand, in contact lens wearers, wearing the contact lenses causes symptoms such as discomfort such as eye irritation, difficulty in seeing, and dryness. And, to improve various symptoms caused by contact lens wearing To this end, Japanese Patent Application Laid-Open No. 2001-192333 proposes an ophthalmic composition for contact lenses containing (A) an amino acid and / or a salt thereof and (B) a cooling agent. The combined use of the B component can reduce the loss of corneal cells and the occurrence of shape abnormalities caused by wearing a contact lens as compared to the case where they are included alone, and can also reduce foreign body sensation when wearing a contact lens. The power to reduce pleasure is revealed.

In recent years, the number of patients complaining of dry eyes and discomfort due to wearing of contact lenses, V-DT work, and the like has become extremely large.

For patients who complain of such symptoms, the use of artificial tears has been conventionally recommended, but such artificial tears and other eye drops may be used immediately after instillation. Although the effect of reducing the feeling of dryness can be obtained, there was a problem that the effect was not persistent.

For this reason, in order to maintain the effect of reducing the feeling of dryness, such an ophthalmic solution is mixed with a thickener or the like to improve wettability or prolong the residence time of the ophthalmic solution on the cornea. Although this has been done, it was not possible to obtain a sufficient effect. Also, when a large amount of a thickener is added to the ophthalmic solution, the viscosity of the solution may become too high, causing a problem such as discomfort when instilled.

Japanese Patent Application Laid-Open No. 2001-322936 discloses that in order to prevent and improve the dry feeling of eyes (dry eye), (A) sodium hydrogen carbonate, (B) lower polyhydric alcohols having 5 or less carbon atoms, Ophthalmic compositions containing at least one compound selected from the group consisting of sugar alcohols and terpenoids have been proposed, and by using these A component and B component together, It has been clarified that various symptoms such as discomfort are improved. Further, Japanese Patent Application Laid-Open No. 2001-122774 proposes an ophthalmic composition for a soft contact lens containing a cooling agent and a polyhydric alcohol, whereby the adsorption of the cooling agent to a soft contact lens is proposed. At the same time as soft contact lens Has been shown to be reduced.

On the other hand, Japanese Patent Application Laid-Open Publication No. 2002-104971 discloses an ophthalmic preparation containing a menthol glycoside containing a monosaccharide such as N-acetyl dalcosamine in its structural formula. A composition for use has been proposed to improve the refreshing sensation and sustainability without increasing eye irritation. However, the menthol glycoside (darcosamine derivative) containing such a monosaccharide bond has menthol as a basic skeleton, and its structure is clearly different from that of the specific amino sugar derivative used in the present invention. It is different. DISCLOSURE OF THE INVENTION

Here, the present invention has been made in view of such circumstances, and a problem to be solved is to prevent swelling / shrinkage of the contact lens while sufficiently providing safety to the eyes. And achieves excellent lens adaptability that does not cause size change, and reduces the discomfort and dryness of the eyes when wearing contact lenses and VDT work, and the effect of reducing the effects is maintained advantageously An object of the present invention is to provide an ophthalmic liquid preparation which can be used.

Another problem is that when the ophthalmic liquid composition is used as a liquid lens composition for contact lenses to which a bactericide is added, specifically, a germicidal solution for contact lenses or MPS It is intended to effectively improve the bactericidal action of a bactericide in a liquid composition when used as a liquid composition.

As a result of repeated studies to solve such problems, the present inventors have conventionally used contact lens sterilizing solutions, cleaning solutions, storage solutions, rinsing solutions, MPS, etc. By adding a specific amino sugar derivative to the contact lens solution or ophthalmic solution, the size of the contact lens may not be changed, and the contact lens may be used when wearing the contact lens or during VDT work. It has been found that it is possible to advantageously reduce the occurrence of discomfort and dryness in the eyes, and that the effect of reduction can be maintained for a long time or for a long time. Also, such specific If the amino sugar derivative is added to a contact lens disinfectant solution or a contact lens disinfectant, MPS, etc., especially in contact lens solution compositions, the disinfectant effect of the disinfectant can be effectively improved. We also found out what we could get.

Accordingly, the present invention has been completed based on such findings, and the gist of the present invention is that it is represented by the following general formula (I) and the following general formula (Π) in an aqueous medium. An ophthalmic solution composition comprising at least one amino sugar derivative.

[Wherein, and independently, a hydrogen atom and a carbon number :! To 18 hydrocarbon groups, — — ^RL , or CH ₂ — — R ¹ . And伹,. R ¹ is,

o o

— OH,. —ONa, one OK, or carbon number:! Represents up to 18 hydrocarbon groups. ]

[Wherein, ³ and ⁴ each independently represent a hydrogen atom, a hydrocarbon group having 1 to 18 carbon atoms, ——R ² , or —CH ₂ —C—RS. However, R2 is

o o

Represents one OH, one ONa, one OK, or a hydrocarbon group having 1 to 18 carbon atoms. ]

In short, in the ophthalmic solution composition according to the present invention, at least one of the specific amino sugar derivatives represented by the general formula (I) or the general formula (Π) is used. Since the seed is included as one of the components constituting the ophthalmic solution composition, the addition of such an amino sugar derivative makes it possible to use a contact lens or overuse the eyes, as compared with conventional ones. During VDT work, various symptoms caused by wearing contact lenses, VDT work, etc., such as foreign body sensation, irritation to the eyes, difficulty in seeing, etc. This can be advantageously reduced, and such a reduction effect can be maintained for a long time or a long time by a specific amino bran derivative.

In addition, since the specific amino sugar derivative added according to the present invention does not cause the contact lens to swell or shrink, the change in the size of the contact lens is advantageously prevented, and excellent lens compatibility is obtained. Can be realized.

In addition, if such a specific amino derivative is added, the bactericidal action of a bactericide that can be added to an ophthalmic solution composition such as a bigger bactericide or a quaternary ammonium salt bactericide can be improved. Thus, the bactericide can be effectively improved, so that even if the concentration of the bactericide in the solution is kept low, a high bactericidal effect can be obtained advantageously. For this reason, the advantage that the safety to eyes can be further improved can be enjoyed.

The amino sugar derivative represented by the general formula (I) includes dalcamine or a derivative thereof represented by the following general formula (ΠΙ), while the amino sugar derivative represented by the general formula (Π) Examples thereof include gnorecosamine represented by the following general formula (IV) or a derivative thereof, and galactosamine represented by the following general formula (V) or a derivative thereof.

[Wherein, ¹ and ² each independently represent a hydrogen atom, a hydrocarbon group having 1 to 18 carbon atoms, 1 —R or 1 CH ₂ —C—R ¹ . Where R ¹ is

o 6

Represents one OH, —ONa, one OK, or a hydrocarbon group having 1 to 18 carbon atoms. ]

[Wherein, ^{3 and} ⁴ each independently represent a hydrogen atom, a hydrocarbon group having 1 to 18 carbon atoms, —CR ² , or one Cfl ₂ —C—R ² . Where R ² is

O 6

-OH, one ONa, one OK, or a hydrocarbon group having 1 to 18 carbon atoms. ]

[Wherein, ³ and ⁴ each independently represent a hydrogen atom, a hydrocarbon group having 1 to 18 carbon atoms, one C—R ² , or one CH ₂ —C—R ² . Where R ² is

6 &

—OH, —ONa, —OK: or represents a hydrocarbon group having 1 to 18 carbon atoms. ]. Further, according to one preferred embodiment of the ophthalmic solution composition according to the present invention, the glucamine represented by the general formula (HI) or a derivative thereof includes N-methyl-D (-)-dalmin or N —Alkyl-1-N-methyl-1-D-glucamine is advantageously employed, and N-acetyldarcosamine or dalcosamine is advantageously employed as dalcosamine represented by the general formula (IV) or a derivative thereof; Further, as the galactosamine represented by the general formula (V) or a derivative thereof, N-acetylgalactosamine or galactosamine can be advantageously used.

Further, according to another preferred embodiment of the ophthalmic solution composition according to the present invention, the aminosugar derivative is contained in a ratio of 0.0001 to 10 wZw%. However, it is desirable. By adopting such a content, it is possible to obtain an excellent effect of improving symptoms such as discomfort / dryness of the eye and an excellent effect of such an effect while advantageously ensuring safety for the eyes. You can enjoy a sustained action. Further, even when the lens is brought into contact with a contact lens, it is possible to advantageously prevent the lens standard from being changed.

In addition, according to another preferred embodiment of the present invention, a configuration in which boric acid or a salt thereof is further contained is suitably searched for. As described above, by using boric acid or a salt thereof in combination with the amino sugar derivative, the preservability of the ophthalmic solution composition can be effectively improved, and preservation for a longer period can be achieved. In addition, more excellent pH buffering ability can be expressed, and the pH change due to mixing of acid or alkali can be suppressed as much as possible, so that the desired pH value can be stably maintained. It becomes like that.

According to still another preferred embodiment of the ophthalmic solution composition according to the present invention, the amino sugar derivative and the boric acid or a salt thereof are in a molar ratio of 1: 100 to 100: 1. The boric acid or a salt thereof is desirably contained in a proportion of 0.001 to 10 wZw%.

Further, according to another preferred embodiment of the ophthalmic solution composition according to the present invention, Preservatives, fungicides, chelating agents, tonicity agents, buffers, thickeners, surfactants, anti-inflammatory agents, decongestants, antiallergic agents, fresheners, flavoring agents, vitamins and amino acids At least one of the classes is further included, so that additional functions according to the components are added.

The ophthalmic solution composition as described above is preferably used as a contact lens solution composition or an ophthalmic composition. When used as a liquid composition for contact lenses, symptoms such as discomfort and dryness of the eyes due to amino sugar derivatives adhering and adsorbing to the contact lenses due to washing, storage, sterilization, and rinsing of the contact lenses. However, it will be reduced over a long period of time or over a long period of time. When a bactericide such as a biguanide bactericide or a quaternary ammonium salt bactericide is added to the contact lens liquid composition, the bactericidal action can be effectively improved. That would be. On the other hand, when the composition is used as an ophthalmic composition, the ophthalmic composition reduces symptoms such as discomfort and dryness of the eye over a long period of time or over a long period of time. In addition, the specific amino sugar derivative added according to the present invention adversely affects the contact lens by changing the standard such as the diameter of the contact lens and the base carp by swelling or shrinking the contact lens. Because it does not give any eye contact, it does not matter whether or not a contact lens is worn when instilling.

By the way, in the general formula (前記), the general formula (IV), and the general formula (V), the viranose-type structural formula having a cyclic structure is described, respectively. The compounds represented by these structural formulas Can be represented by an aldehyde type having a chain structure, as is well known.In the present invention, any of such a vilanose-type structure and an aldehyde-type structure are asked. That is not to say, of course. BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows the buffer capacity of the buffers according to Nos. 1 to 4 obtained in the examples. It is a graph showing.

FIG. 2 is a graph showing the buffer capacity of buffers Nos. 5 to 8 obtained in the examples. BEST MODE FOR CARRYING OUT THE INVENTION

By the way, the ophthalmic solution composition according to the present invention is mainly composed of an aqueous medium such as purified water, in which a specific amino sugar derivative is contained, and has particularly remarkable features. It is doing.

Specifically, the specific amino sugar derivative used in the present invention is an amino sugar derivative represented by the general formula (I) or the general formula (式), and such a specific amino sugar derivative is Inclusion of at least one derivative causes various symptoms such as discomfort and dryness such as irritating eyes and difficulty in seeing eyes when wearing contact lenses or performing VDT work that overuses the eyes. Can be advantageously reduced, and the reduction effect can be continued for a long time or a long time.

In addition, as described above, amino sugar derivatives that reduce discomfort and dryness when wearing contact lenses or VDT work do not adversely affect the physical properties, shape, size, etc. of contact lenses. The liquid composition containing such an amino sugar derivative is provided with the properties required for the contact lens liquid composition, that is, excellent lens compatibility. Furthermore, when used as an ophthalmic composition, it may be possible to apply the eye while wearing the contact lens on the eye, since it does not adversely affect the raw material, shape, size, etc. of the contact lens. Come.

In the general formula (I), X ¹ ′ X ² each independently represent a hydrogen atom, a hydrocarbon group having 1 to 18 carbon atoms, one CO—R ¹ , or one CH ₂ —COR ¹ Is shown. X ³ and X ⁴ in the general formula (Π) are each independently a hydrogen atom, a hydrocarbon group having 1 to 18 carbon atoms, _CO—R ² , or CH ₂ -CO- ² is shown. Here, the "hydrocarbon group having 1 to 18 carbon atoms" includes a linear, branched or cyclic alkyl group or alkenyl group, and among them, the carbon group having 1 to 4 carbon atoms is preferred. A lower alkyl group or lower alkyl group is desirable.

Another aspect CO- R ^1, one _{^{CH 2 -CO-R 1, -CO}} -R 2, and R ¹及Pi R ² in one CH ₂ -CO-R ² are each one OH, one ON a, -OK, or a hydrocarbon group having 1 to 18 carbon atoms, and as R ¹ and R ² “hydrocarbon groups having 1 to 18 carbon atoms” as described above, And a branched or cyclic alkyl group or an alkyl group. Among them, a lower alkyl group or a lower alkenyl group having 1 to 4 carbon atoms is preferable.

However, as is clear from the general formula (I) and the general formula (前記), the amino sugar derivative represented by the general formula (I) and the general formula (Π) has an asymmetric carbon atom. Multiple isomers exist from multiple places. In the present invention, the compounds represented by the general formula (I) and the general formula (Π) are not limited as long as they are compounds represented by the general formula (I). The glucamine represented by the general formula (ΙΠ) or a derivative thereof is preferably employed as the amino sugar derivative represented by the general formula (採用), while the amino sugar derivative represented by the general formula (Π) is preferably the general formula: Darcosamine (also called chitosamine) represented by (IV) or a derivative thereof, and galactosamine represented by the general formula (V) or a derivative thereof can be suitably adopted.

Among the amino sugar derivatives represented by the general formulas (ID) to (V) as described above, N-methyl-D (-)-glucamine (also called meglumine), N-alkyl-N-methyl-D -Glucamine, glucamine, N-acetyl dalcosamine, N-acetyl galactosamine, dalcosamine, and galactosamine are more preferably employed because they are particularly excellent in safety for living bodies. . Furthermore, among them, N-acetyldarcosamine is involved in the regulation of the body's defense immune system and the balance of electrolytes, and has a high water-retaining ability, "hyaluronic acid". Since it is involved in the production, symptoms such as discomfort and dryness of the eyes can be more effectively reduced, and the effect of the reduction can be advantageously achieved.

In the present invention, at least one or two or more of the amino sugar derivatives represented by the general formula (I) and the general formula (H) are appropriately selected, and the aqueous medium It will be dissolved and contained inside. The content is appropriately set so that the effect of reducing discomfort and dryness can be advantageously obtained, but in the present invention, the content is 0.1% of the total amount of the liquid composition. A ratio of 0.001 to 10% by weight (w / w%), preferably 0.001 to 5.0% by weight is suitably adopted. This is because, if the content of the amino sugar derivative is less than 0.0001% by weight, the effect of adding the above specific amino sugar derivative may not be sufficiently obtained. In addition, if the content exceeds 10% by weight, it may cause irritation to the eyes and impair the eye, and may adversely affect the contact lens, such as a change in size. . Thus, the ophthalmic solution composition according to the present invention is prepared by adding and dissolving such a specific amino sugar derivative in an appropriate amount in an appropriate aqueous medium in the same manner as before. However, in the present invention, in addition to such a specific amino sugar derivative, depending on the purpose of use and the like, furthermore, there are known liquid lens compositions for contact lenses and known ophthalmic compositions used in ophthalmic compositions. Various additive components, such as preservatives, bactericides, chelating agents, tonicity agents, buffers, thickeners, surfactants, anti-inflammatory agents, decongestants, antiallergic agents, fresheners, and flavors There is no problem even if the preparations, vitamins, amino acids and the like are appropriately selected and contained within the usual range. In addition, it is preferable that all of these various additive components are safe for the eyes and do not adversely affect the shape or physical properties of the contact lens. It will be used within the range. Thereby, various functions corresponding to the added components can be advantageously imparted to the ophthalmic solution composition without impairing the effects of the present invention at all. For example, in order for the ophthalmic solution preparation of the present invention to advantageously exhibit the disinfecting or bactericidal effect of the eyes and contact lenses, and furthermore the antiseptic * preserving effect of the ophthalmic solution composition, An antiseptic or bactericide having a preservative or bactericidal effect can be added. In addition, it is desirable that such preservatives and bactericides be those that have excellent antiseptic or bactericidal efficacy, and that are highly compatible with ocular contact lenses, and that are less likely to cause allergies or other obstacles. Appropriate ones are selected from various known ones, and used alone or in combination.

Incidentally, the preservatives include, for example, sorbic acid, potassium sorbate, benzoic acid or a salt thereof, paraethyl benzoate, ethyl parabutyl benzoate, butyl parahydroxybenzoate, propyl parahydroxybenzoate, methyl parahydroxybenzoate, chlorobutanol, peroxybenzoic acid Alternatively, perborate such as sodium perborate, chlorine dioxide, stabilized chlorine dioxide and the like can be mentioned. Examples of the bactericide include a biguanide bactericide and a quaternary ammonium salt bactericide. Such conventionally known ones can be appropriately selected and employed. Among them, polyhexamethylene is particularly preferred because it achieves a high bactericidal effect even at a low concentration and is excellent in safety. Biguanide (P HMB), Polyquaternium-1 (trade name: Polyquad), Polymeric 4th grade An ammonium compound (for example, ionone) will be preferably used. When the preservative or bactericide is not used, and the ophthalmic composition according to the present invention is used, particularly when used as an ophthalmic composition, the ophthalmic composition may be used at a time. A single dose type that can be used up, or a multi-use using a filter-equipped discharge container in which a membrane filter is attached to a nozzle portion of an eye drop container as disclosed in Japanese Patent Application Laid-Open No. 2002-80055. It is also possible to use a dose type.

Further, the ophthalmic solution composition containing such a disinfectant is advantageously used as a contact lens solution composition, particularly, a contact lens disinfectant solution, MPS, etc. However, in the liquid composition for contact lenses according to the present invention, a specific amino sugar derivative represented by the general formula as described above is used. Since the conductor is contained, the bactericidal action of the bactericide can be effectively improved by such a specific amino sugar derivative. Even if it is kept low, a high bactericidal effect can be obtained advantageously. In addition, such a bactericide is usually 0.00000001 to 0.3 weight. When used in a concentration range of about / ₀ (w / w%), a particularly effective bactericidal effect is exhibited.

Furthermore, since contact lenses, especially soft contact lenses, generally have the possibility that calcium or the like may be deposited or adsorbed as dirt from tears, it is necessary to prevent such calcium or the like from being deposited or adsorbed. However, a chelating agent will also be advantageously added to the ophthalmic solution composition. Examples of such chelating agents include ethylenediaminetetraacetic acid (EDTA) and salts thereof, such as ethylenediaminetetraacetic acid disodium (EDTA * 2Na) and ethylenediaminetetraacetic acid / 3 sodium (EDTA * 3Na). Such a chelating agent is contained in a liquid within a quantitative range that does not inhibit the action * effect of the present invention.

In addition, in the ophthalmic solution composition according to the present invention, if the pH value or the osmotic pressure is too large or too small, it may cause irritation to the eyes, Normally, it is desirable to adjust the pH value to about 5.3 to 8.5, especially to about 7.0, because it may cause harm. In addition, it is also possible to add a pH adjuster such as sodium hydroxide / hydroxide power, hydrochloric acid, or a buffer.

The buffering agent is appropriately selected and used from various conventionally known ones. Specifically, acids such as phosphoric acid, boric acid, carboxylic acid, and oxycarboxylic acid, and salts thereof (for example, sodium salt, etc.), and furthermore, Good-Buffer-tris (hydroxymethyl) aminomethane, bis ( 2-Hydroxityl) Iminotris (hydroxymethyl) methane, sodium bicarbonate, etc., are safe for the eyes and reduce the effect on contact lenses Because we can do it, we can list it.

In particular, in the present invention, among the buffering agents described above, boric acid such as boric acid, borax, ammonium borate or a salt thereof is preferably used. The reason is that by using boric acid or a salt thereof in combination with a specific amino sugar derivative which is an essential component in the present invention, the preservability of the ophthalmic solution composition can be effectively improved, and a longer term Over a long period of time, and a more excellent pH buffering ability can be expressed, and the pH change due to the contamination of acid or alkaline can be suppressed as much as possible. This is because the value can be stably held. Incidentally, the addition of boric acid or a salt thereof enables the ophthalmic solution composition to be preserved for a longer period of time, and further excellent pH buffering ability can be expressed by boric acid. The present inventors presume that the acid or salt thereof is caused by forming a complex with the amino bran derivative represented by the general formula (I) or (式) as described above.

Further, such a boric acid or a salt thereof may have a molar ratio (amino sugar derivative: boric acid or a salt thereof) with the amino sugar derivative represented by the general formula (I) or (Π) as described above, It is desirable to add such that the ratio becomes 1: 100 to 100: 1, and by adopting such a ratio, the effect of adding boric acid or a salt thereof is advantageous. Will be realized.

Further, the content of boric acid or a salt thereof in the ophthalmic solution composition is 0.0001 to 10% by weight of the total amount of the solution composition. An amount of / o (w / w%) can be suitably adopted. This is because if the content is less than 0.001 wZw%, the above-mentioned effects obtained by adding boric acid or a salt thereof cannot be sufficiently exerted. If it exceeds w / w%, it becomes difficult to dissolve boric acid or a salt thereof.

On the other hand, the osmotic pressure is generally adjusted by adding a tonicity agent so that the osmotic pressure is in the range of about 200 to 40 OmOs mZ kg, which is substantially equal to the physiological osmotic pressure. Preferably. The isotonicity used for such osmotic adjustments As the agent, at least one compound selected from the group consisting of sodium chloride, potassium chloride, saccharides, sugar alcohols, and polyhydric alcohols or ethers or esters thereof is generally used.

Further, in the present invention, in order to appropriately adjust the viscosity of the ophthalmic solution composition, and in particular, when used as an ophthalmic composition, to extend the residence time of the amino sugar derivative on the cornea,ことが It is useful to add a thickener. Examples of the thickener include various gums such as mucopolysaccharides such as chondroitin sulfate, hyaluronic acid, dalconic acid, and salts thereof; Synthetic organic high molecular compounds such as ridone, polyethylene glycol, polypropylene glycol / polyacrylamide, etc .; Cellulose derivatives such as hydroxyethyl senorellose, hydroxypropyl / remethinolese / rerose, carboxymethyl senorellose, methinoresenolose; starch derivatives etc. The thickener will be used.

Further, the ophthalmic solution composition according to the present invention may contain various known surfactants in order to advantageously exert the effect of removing dirt such as eye oil (cleaning effect). . As the surfactant, a surfactant which is highly safe for living organisms and has no influence on the contact lens can be used as long as it is a known surfactant, a nonionic surfactant, or an amphoteric surfactant. Both the surfactant and the cationic surfactant can be employed, and they can be advantageously added or contained at a concentration that does not impair the effects of the present invention.

Specific examples of such surfactants include, for example, glycerin fatty acid esters such as glyceryl monostearate, polyglycerin fatty acid esters, polyoxyethylene glycerin fatty acid esters, and polyoxyethylenes such as polyoxyethylene lauryl ether. Ethylene alkyl ether, polyoxyethylene polyoxypropylene block copolymer, polyoxyethylene. Polyoxypropylene ethylene diamine, polyoxyethylene / polyoxypropylene anolyl ether, polyoxyethylene sorbitan monoolate (for example, polysorbate 8 0) etc., polyoxyethylene sorbitan fatty acid esters (polysonolate), sorbitan fatty acid esters such as sorbitan sesquioleate, polyoxyethylene sorbite fatty acid esters, polyoxyethylene alkyl phenyl ether, and boroxy acids such as oxaxapol Ethylene alkyl phenyl ether formaldehyde condensate, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyethylene sterol, polyoxyethylene hydrogenated sterol, polyoxyethylene fatty acid ester such as polyethylene glycol monostearate, Polyoxyethylene lanolin alcohol, polyoxyethylene olenoquinamine, polyoxyethylene alkyl amide, polyoxyethylene alkyl ether phosphorus Acids and the like can be mentioned. Among them, in particular, the polyoxyethylene-polyoxypropylene block copolymers punorelook, punorelonic R, tetronic, and tetronic R, which are commercially available as nonionic surfactants (above, BASF Germany) Poloxamer 124, poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, tetronic 904, tetronic 908, tetronic 13 It is preferable to use 0.4, Tetronic 110, and polysonolate 80, which is polyoxyethylene sorbitan monoolate.

In addition, the ophthalmic composition according to the present invention, particularly the ophthalmic composition, includes dipotassium glycyrrhizinate, allantoin, berberine chloride, berberine sulfate, sodium azulene sulfonate, zinc sulfate, zinc lactate, Antiphlogistics such as lysozyme; decongestants such as epinephrine, ebinefrine hydrochloride, efuedrine hydrochloride, naphthozoline hydrochloride, naphazoline nitrate, ferrefrine hydrochloride, tetrahydrozoline hydrochloride; antihistamines such as diphenhydramine hydrochloride, chlorpheniramine maleate; Sulfa drugs such as methoxazonole, sulfamethoxazoline / resodium, sulfisoxazole, sulfisomidine sodium, etc .; antiallergic drugs such as cromoglycic acid, sodium cromoglycate, tranilast, pumilolast potassium; c. Cool oil, d-Camphor, d1-Camphor, Cool mint N 0, 7 1 2 1 2, Galley No. 1 / Nore, Nore water, Nore oil, Beregamot oil, d-Borneo-nore, d1-Bonorneo-nore (Ryuno), 1-mento-nore, d1-menthol, eucalyptus oil, linalore , N-ethyl-p-menthan-3-carboxyamide (eg, WS-3; Takasago International Corporation); ascorbic acid, L-aspartic acid, sodium L-aspartate, magnesium L-aspartate , Aspartame, Amachia, Amachiya extract, Amachiya powder, Aminoethinolesnolephonic acid, Wikiyo, Wikiyotin tincture, Wikiyo powder, Wikiyo oil, erythritol, Kanzo, Kanzo extract, D-so / rebitone sugar, D-sono-renototo Flavor adenine dinucleotide sodium (active Type vitamin B _2), hydrochloric acid pyridinium Dokishin (vitamin B _6), Shianokobaramin (vitamin B _{1 2),} vitamin E acetate, panthenol, calcium pantothenate, sodium pantothenate, retinol acetate, retinol palmitate (vitamin A Parumite Vitamins such as g); amino acids such as aspartic acid and salts thereof, aminoethylsulfonic acid, arginine, alanine, lysine, glutamic acid, ε-aminocaproic acid, and the like can be appropriately added.

By the way, the powerful ophthalmic solution composition according to the present invention is prepared by adding and containing the above-mentioned components in appropriate aqueous media in appropriate amounts in the same manner as in the prior art. However, the aqueous medium used at that time may be a water-based solution other than water itself such as tap water, purified water, or distilled water, and may be a physiological saline solution or an aqueous solution containing sodium chloride. It goes without saying that known contact lens solutions and eye drops can be used.

In preparing the ophthalmic solution composition according to the present invention containing the specific amino sugar derivative or the like as described above, no special method is required, and the same as in the case of preparing an ordinary aqueous solution It can be easily obtained by dissolving each component in an aqueous medium.

And the ophthalmic solution thread composition according to the present invention obtained as described above, for example, Disinfectant for contact lenses, contact lens cleaning solution, contact lens preservation solution, contact lens rinsing solution, etc., as well as multiple cleaning with one type of liquid, cleaning * preservation solution, cleaning '' It can be advantageously used as a liquid composition for contact lenses such as a multipurpose liquid (MPS) such as a preservation / rinse liquid, a sterilization / cleaning liquid, and an ophthalmic composition such as an ophthalmic solution.

For example, when the ophthalmic solution composition according to the present invention is used as a sterilizing solution for contact lenses among contact lens solution compositions, and when the contact lenses are to be cared for, the contact lenses removed from the eyes must first be removed from the contact lens. The germicidal disinfection is performed by immersing in a suitable container filled with the contact lens solution composition according to the present invention for a predetermined time. When the contact lens is worn again, the contact lens is taken out of the liquid, washed, and then worn.In such a case, the disinfected contact lens is washed with a saline solution or the like. You may just rinse with Furthermore, if the concentration of the disinfectant is low and the safety to the eyes is ensured, remove the contact lens immersed in the liquid composition and directly apply it to the eyes. It is also possible to wear. Also, such contact lens disinfection can be performed at all after a separate contact lens cleaning operation.

When the ophthalmic solution composition according to the present invention is used as a solution composition for a contact lens, the type of the contact lens to be used is not limited at all. Soft contact lenses and hard contact lenses that are classified into all types, such as low water content and high water content, can be used as targets, and the material of the contact lens and the like are not limited when applying the ophthalmic solution composition according to the present invention. You will not be asked. Among them, the ophthalmic solution composition according to the present invention has excellent lens compatibility, so that it can be particularly advantageously applied to a soft contact lens in which a size change is easily caused. ing.

Further, the ophthalmic solution composition according to the present invention is used as an ophthalmic composition, When prescribing for eyes with symptoms such as eyes, an appropriate amount may be instilled in the same manner as conventionally known eye drops or eye drops. In this case, since the ophthalmic composition according to the present invention does not have any adverse effect on the physical properties and shape of the contact lens, it does not matter whether or not the contact lens is worn in the eye drops. Therefore, as described above, the ophthalmic solution preparation according to the present invention may be used as an ophthalmic composition for a VDT worker, Contacta I, a lens wearer, etc. who complain of symptoms such as discomfort and dryness. However, a specific amino sugar derivative can be effectively supplied into the smelt ball, so that symptoms such as discomfort and dryness can be effectively improved, and such a reduction effect is long. It can be played over time. In addition, for a contact lens wearer, not only the symptoms such as discomfort and dryness can be improved but also the feeling of wearing the contact lens can be improved. Example

Hereinafter, examples of the present invention will be shown to clarify the present invention more specifically.However, it should be understood that the present invention is not limited by the description of such examples. , It goes without saying. In addition, in addition to the following examples, and in addition to the above-described specific description, various changes and modifications may be made to the present invention based on the knowledge of those skilled in the art without departing from the spirit of the present invention. It should be understood that modifications and improvements can be made.

(1) Contact lens liquid composition

—Lens compatibility test 1

For a given amount of sterilized purified water, a nonionic surfactant (poloxamer 407; manufactured by BASF), a thickener (methrose 60 SH-4000; manufactured by Shin-Etsu Chemical Co., Ltd.), a chelating agent (EDTA '2Na ), A bactericide (PHMB), a tonicity agent (propylene glycol, NaCl), and a buffering agent (boric acid) in various proportions shown in Table 1 below, respectively. The dalkamine derivative (medalmine) represented by the formula (m) is converted to 0.1 w / w%, or The liquid compositions for contact lenses according to Examples 1 to 3 were separately manufactured by adding them so that the pH was 7.3. The amount of sterilized purified water was adjusted so that the total amount of the various components described above would be 100 w / -w%.

On the other hand, commercially available soft contact lenses (Menicon Soft MA, Menicon Soft 72; manufactured by Menicon Co., Ltd.) were prepared, and these were placed in physiological saline (ISO 10) maintained at a temperature of 25 ° C. 3 4 4) After immersion, the lens size (diameter) of each contact lens was measured using a projector (Nikon Corporation's universal projector) under the immersion condition. The measured values were each recorded as a lens diameter (D.).

Next, the contact lens thus determined for the initial value of the lens diameter was immersed for 7 days in the contact lens liquid composition according to Examples 1 to 3 maintained at 25 ° C. While maintaining the immersion state, the lens size is measured in the same manner, and the obtained value (0 ェ) is subtracted from the initial value (D.) obtained in advance to obtain the amount of change in the lens size. Was calculated, and the results are shown in Table 1 below. It is needless to say that the smaller the absolute value of the amount of change of the lens size is, the more excellent the suitability for the contact lens is, and the value of the amount of change is desirably within ± 0.2 mm. ing.

Example

one two Three

Poloxamer 407 0.5 0.5 0.5

Attached metrose 60SH-4000 0.275 0.275 0.275

Caro

EDTA-2Na 0.05 0.05 0.05

Combination

PHMB 0.0001 0.0001 0.0001

Propylene glycol 0.5

/

W NaCl 0.85 0.65 0.45

% Boric acid 0.5 0.5

Megnoremin 0.1 Appropriate amount

Size change Menicon Soft MA 0.00 0.04 0.16

[mm] Mac software 72 0.13 0.12 0.10

* 1: Added to pH 7.3

As is clear from the results in Table 1 above, even if medalmin is added, the size change of the contact lens is as small as 0 to 0.16 mm, and meglumine does not affect the shape (diameter) of the contact lens. Is recognized. In addition, it can be said that the liquid composition for contact lenses according to Examples 1 to 3 has excellent lens compatibility. As described above, the medicamine-added contact lens liquid composition is excellent in compatibility with lenses, and therefore is not limited to use as a preservative solution or contact lens liquid such as MPS. It is also recognized that it can be used as a thread for eye drops to be instilled when wearing contact lenses.

—Disinfection effect test—

For a predetermined amount of sterilized purified water, a nonionic surfactant (poloxamer 407; manufactured by BASF), a viscous agent (methrose 600 SH-40000; manufactured by Shin-Etsu Chemical Co., Ltd.), a chelate Agent (EDTA * 2Na), fungicide (PHMB), tonicity agent (propylendalcol), buffer (boric acid, borax, L-arginine, trometamol; Sigma Aldrich, Citrate, sodium dihydrogen phosphate, sodium hydrogen phosphate, Bis-Tris), pH adjuster (hydrochloric acid, sodium hydroxide), and glucamine derivative (medalmine) represented by the general formula (II) In Table 2 below The liquid compositions for contact lenses according to Examples 4, 5 and Comparative Examples 1 to 7 were respectively prepared by adding them at the various ratios shown. The amount of sterilized purified water was adjusted so that the total amount of the various components mentioned above would be 10.0.

Then, 9.9 mL of each of the contact lens liquid composition according to Examples 4 and 5 and Comparative Examples 1 to 7 obtained above was put into a test tube, and Candida was used as a test bacterium. - Albi force Nsu {Candida albicans IFO 1594), Staph Gray Lactococcus Aure mortar {Staphylococcus aureus ^ IFO 13276), or Fuzariumu solani the (Fusariu solani IFO 36031), 1 0 8 ~:. 1 0 9 cf \ 1 Roh 1111 adding 0. I mL of bacterial suspension was stirred including ^, finally bacterial suspension containing cell count ^{^{1 0 6 ~1 0 7 cfu /}} mL, and their respective preparation. Then, after leaving them at 23 ° C for 4 hours, ImL of the bacterial suspension was taken out, and the number of viable bacteria in the sample ImL was measured by the plate dilution method using 2 OmL of glucose peptone agar medium. did. Then, after calculating the number of viable bacteria in the treated solution I mL from this viable cell count, the log reduction converted to logarithm was calculated according to the following formula, and the result was calculated as shown in Table 2 below. It was shown to.

Number of bacteria reduced = l o g (number of viable bacteria in ImL of bacterial suspension immediately after preparation)

-log (number of viable bacteria in ImL of bacterial suspension after treatment)

Table 2

* 1 Added to pH 7.3

As is evident from the results in Table 2, in the liquid lens compositions for contact lenses according to Examples 4 and 5 containing medalmin, the number of reduced bacteria of three types of bacteria was comprehensively measured. Judging from the above, it was confirmed that the bactericidal effect was superior to that of other liquid drug compositions that did not contain meglumine. You can judge that you have improved. On the other hand, in Comparative Examples 5 and 6 in which cunic acid or phosphoric acid was contained, the number of bacteria reduced in L. albicans was less than 1.0, and as a sterilizing solution for contact lenses. Cannot be used.

—Lipid washing effect test .Bactericidal effect test—

For a predetermined amount of sterilized purified water, a dalcosamine derivative (N-acetyldarcosamine) represented by the general formula (IV), a nonionic surfactant (poloxamer 407; manufactured by BASF), Viscous agents (hydroxypropyl methylcellulose), chelating agents (EDTA-2Na), buffers (boric acid, borax), tonicity agents (sodium chloride, potassium chloride), and fungicides ( PHMB) was added in various proportions shown in Table 3 below to prepare liquid compositions for contact lenses according to Example 6 and Comparative Example 8, respectively. The amount of sterilized purified water was adjusted so that the total amount of the various components described above would be 100 wZw%.

Then, the washing effect on lipids of the contact lens liquid composition according to Example 6 and Comparative Example 8 obtained above was confirmed by a lipid solubilization rate method. That is, 99% of triglyceride (Pharmazol B-112; manufactured by NOF Corporation) as a lipid and Sudan I (maximum absorption wavelength: 485.5 nm; manufactured by Nacalai Tesque, Inc.) Preparing a colored lipid prepared by mixing at a weight ratio of 1: 0.5 mL and weighing it with a continuously variable volume pipette (100-1000 μL) After being accommodated in a bottle, 15 mL of the contact lens liquid composition of Example 6 or Comparative Example 8 obtained above was further added to the test bottle, and then the test bottle was opened. The part was covered with a suitable lid.

Each test bottle was then shaken at a constant speed for 24 hours at a temperature of 25 ° C. After allowing the mixture to stand for a predetermined time, the supernatant in each test bottle was collected, and each of the supernatants was subjected to a spectrophotometer (manufactured by Shimadzu Corporation: self-recording spectrophotometer UV-2400). PC), the absorbance at a wavelength of 435.5 nm was measured. Then, the absorbance ratio (absorbance ratio) of Example 6 was calculated based on the absorbance of the supernatant containing the liquid composition of Comparative Example 8, and the results are shown in Table 3 below. Here, the fact that such an absorbance ratio is greater than 1, in other words, that the absorbance is relatively high, means that the lipid has an excellent washing effect on lipids, specifically, an excellent lipid solubilizing ability.

On the other hand, by using Candida albicans C dida albicans IFO 1594) and Staphylococcus aureus Staphylococcus aureus IFO 13276) as the test bacteria, the contact lens solutions according to Example 6 and Comparative Example 8 obtained above were used. The number of bacteria reduced in the composition (log reduction) was determined in the same manner as in Example 4 described above, and the results are shown in Table 3 below. The leaving time was set to 4 hours as in Example 4 above.

Table 3

Example 6 Comparative Example 8

Ν-Acetyl glucosamine 1

Poloxamer 407 0.5 0.5

Attachment

Power tl human, roxif. Lohi. Lumeti V † / Relose 0.15 0.15

Percent

α EDTA2Na 0.05 0.05

W Boric acid 0.5 0.5

/ Borax 0.05 0.05

W

% NaCl 0.275 0.45

KC1 0.055 0.09

PH B 0.0005 0.0005

Lipid washing effect (absorbance ratio) 1.05 1

Albicans〉 3.16〉 3.16

Bacteria reduction

S. aureus> 3.96〉 3.96 As is evident from the results in Table 3 above, the contact lens formulation according to Example 6 containing N-acetyldarcosamine did not contain any. It can be seen that the same lipid cleaning effect as that of the liquid composition for contact lenses according to Comparative Example 8 can be achieved. Therefore, the cleaning effect of the surfactant was not impaired by the addition of N-acetyldarcosamine, and the liquid for contact lenses according to Example 6 containing N-acetyltilcosamine was included. The composition can be advantageously used as a cleaning solution for contact lenses.

(1) Trial test for sterilization, preservation, and rinsing liquid (MPS) for contact lenses (1) For a predetermined amount of sterilized purified water, dalcosamine derivative (N-acetyldarco) represented by the above general formula (IV) Samin), nonionic surfactants (¾ agent (poloxamer 407, tetronic 1107; manufactured by BAS F), thickener (hydroxypropyl methylcellulose), chelating agent (disodium edetate), buffer (Boric acid, borax, Bis-Tris), tonicity agent (sodium chloride), fungicide (PHMB), and pH adjuster (NaOH or HCl) are shown in Table 4 below. The liquid composition for contact lenses according to Examples 7 to 12 and Comparative Examples 9 to 12 whose pH was adjusted to 7.3 by adding each of the various ratios was prepared. The amount of sterilized purified water is as described above. Total combined amount of the various components is the amount to be 10 0 w / w%.

Then, the liquid composition for contact lenses according to Examples 7 to 12 and Comparative Examples 9 to 12 obtained above was converted into a multipurpose liquid (MPS) for washing, disinfecting, storing, and rinsing contact lenses. A trial test was conducted to confirm the effect of reducing and maintaining discomfort and dryness, and to evaluate the lens compatibility of the liquid composition that was strong.

That is, first, the volunteers of the contact lens wearers [10 oxygen wear-resistant hard contact lenses (RGP) wearers + 10 soft contact lenses wear a total of 20 people] Each was used continuously as MPS for one month. When using a contact lens, The lens was rinsed with each MPS, and the lens was worn without being rinsed with tap water or physiological saline.

Then, after a trial period of one month, from each wearer, an answer for evaluation of discomfort / dryness was obtained for each MPS, and evaluation results shown in Table 4 below were obtained from the answer. The following evaluation criteria were adopted.

Evaluation criteria

◎◎ _: Ocular discomfort due to wearing contact lenses or daily life ♦ When the proportion of those who answered that the feeling of dryness was remarkably reduced and the effect lasted was 90% or more.

©: When the discomfort of eyes and dryness due to wearing contact lenses and daily life are remarkably reduced, and the proportion of those who answered that the effect lasted is 70% or more and less than 90%. 〇: When the discomfort of eyes and dryness due to wearing of contact lenses and daily life are remarkably reduced, and the proportion of those who answered that the effect lasted is 50% or more and less than 70%. △: when the discomfort of the eyes due to wearing contact lenses or daily life is remarkably reduced and the proportion of people who answered that the effect lasted is less than 50%.

On the other hand, a commercially available contact lens (Menicon Soft 72; manufactured by Menicon Corporation) was prepared, and the amount of change in the lens size was calculated in the same manner as in Example 1 above. Then, from the calculated size change values, the lens compatibility of the contact lens liquid composition according to Examples 7 to 12 and Comparative Examples 9 to 12 was evaluated according to the following evaluation criteria. Are shown in Table 4 below.

Evaluation criteria

Pass: The size change of all contact lenses is within ± 0.2 mm. Fail: The size change of some contact lenses exceeded 0.2 mm. Four

* 1: Caroline so that pH is 7,3

As is clear from the results in Table 4, the liquid lens compositions for contact lenses according to Examples 7 to 12 are all excellent in lens compatibility. In addition, the contact lens liquid composition according to Comparative Examples 9 to 12 containing no N-acetyldarcosamine had a negative effect of reducing discomfort and a feeling of dryness. Examples 7 to 12 containing darcosamine are ◎◎, and the discomfort and dryness caused by wearing the contact lens can be effectively reduced by the addition of N-acetylcetyl dalcosamine. Is allowed. Boric acid, borax, and a dalcamine derivative (medalmine) represented by the above general formula (m) are dissolved in a predetermined amount of sterilized purified water so as to have the concentrations shown in Tables 5 and 6 below. By dissolving each, buffer solutions according to Nos. 1 to 8 were respectively prepared. Table 5

Then, a predetermined amount of hydrochloric acid or sodium hydroxide was added to 100 O'm 1 of each prepared buffer solution, and the pH was measured. The results are shown in FIGS. 1 and 2. As is clear from FIG. 1, the buffer solution containing both boric acid and medalmin (Nos. 1 to 3) contains a conventional buffer solution consisting of boric acid and borax (No. 4). ), The change in pH is extremely small, indicating that the buffer capacity is advantageously improved. In addition, as is clear from FIG. 2, in the case of a buffer solution in which boric acid and medalmin were used in combination (Nos. 6, 7), the total molar amount was the same, only boric acid or meglumine. It can be seen that the change in pH is extremely small as compared to the buffer solution containing only lipase (Nos. 5, 8), and that excellent buffering capacity is exhibited. One osmotic pressure method

In addition, we speculated that the improvement in buffering capacity achieved by combining boric acid and medalmin might be due to complex formation (complex formation) between boric acid and medalmine, and conducted the following test. . That is, boric acid and medalmine were dissolved in a predetermined amount of sterilized purified water so as to have the concentrations shown in Table 7 below, thereby preparing the sample solutions for Nos. 1 to 9 respectively. Then, the osmotic pressure of each sample solution was measured twice, and the average value of the rates was calculated. The measured values and average values of the obtained osmotic pressure are also shown in Table 7 below.

7

As is clear from the results in Table 7, the osmotic pressure values of the sample solutions (Nos. 7 to 9) containing both boric acid and medalmin were determined for boric acid alone or meglumine. It is presumed that a complex is formed, which is extremely smaller than the sum of the osmotic pressures of the sample liquids containing only these components.

In other words, taking the sample solution of No. 7 (boric acid / meglumine = 0.25 / 1) as an example, if boric acid and medalmin do not form a complex, the osmotic pressure will be only boric acid. The osmotic pressure of the sample solution according to No. 1 (boric acid = 0.25 w / w%) and the sample solution according to No. 6 containing only medalmine (Medalmin = 1.00 w / w%) should be about the sum of the osmotic pressures (42.5 + 54 = 96.4), but the osmotic pressure of the sample liquid related to No. 7 Is 33, which suggests that the complex formation increased the apparent molecular weight and decreased the osmotic pressure.

As is clear from the above description, in the contact lens solution composition according to the present invention, since at least one or more specific amino sugar derivatives are contained, when the contact lens is worn, Symptoms caused by wearing the contact lens, such as a foreign body sensation, irritation to the eyes, discomfort such as difficulty in seeing, and a feeling of dryness, can be advantageously reduced. Such a reduction effect can be maintained for a long time or for a long time by the amino sugar derivative adsorbed on the contact lens.

In addition, since such a specific amino sugar derivative does not cause the contact lens to swell or shrink, a change in the size of the contact lens is advantageously prevented, and a contact lens solution excellent in lens compatibility is provided. It is a composition.

Furthermore, by including the specific amino sugar derivative as described above, the advantage that the sterilizing ability of a bactericide such as a bigger bactericide can be extremely effectively improved can be enjoyed. Become. As a result, even if the concentration of the bactericide in the contact lens liquid composition is kept low, a high bactericidal effect can be advantageously obtained, and thus the safety for the living body can be further improved. You get it. By using the specific amino sugar as described above in combination with boric acid or a salt thereof, the liquid composition for contact lenses can be stored for a longer period of time, and the pH can be increased. The change is more effectively suppressed, and a better pH buffering ability can be realized. (2) Ophthalmic composition

Various ophthalmic compositions having a pH of 6.8 were prepared by adding predetermined additives to sterilized purified water at various ratios shown in Tables 8 to 15 below (Examples 13 to 47). And Comparative Examples 13 to 29) were prepared, respectively. The amount of the sterilized purified water was adjusted so that the total amount of the various components described above was 10 OwZw%. In preparing a powerful ophthalmic composition, N-acetyldarcosamine was used as the amyl / sugar derivative represented by the above general formula (IV), which is an essential component in the present invention. Further, examples of surfactants include Poloxamer 407 (manufactured by BASF), Tetroyuk 1107 (manufactured by BASF), Tetronic 1304 (manufactured by BASF), and polysorbate (polyoxyethylene (20) sorbitan monooleate; Nikko Chemicals Co., Ltd.), and hydroxypropyl methinolate cellulose, hydroxyxetino recellulose, sodium hyaluronate, and sodium chondroitin sulfate were used as viscosity agents. In addition, as a chelating agent, disodium edetate, as a buffering agent, boric acid and borax, and as a preservative or disinfectant, sorbic acid potassium rim and polyhexamethylene biguanide (PHMB), etc. Sodium salt, potassium chloride and propylene dalicol were used as tonicity agents, and 1-menthol and d1 camphor were used as cooling agents, respectively. Then, for each of the obtained ophthalmic compositions, a dryness-reducing sustaining effect test and a lens compatibility test described below were performed.

―Dry feeling reduction effect test―

10 oxygen-permeable hard contact lens wearers, 10 soft contact lens wearers, and 10 VDT workers without contact lenses The following sensory tests were conducted on a total of 30 volunteers. Specifically, during the one-month test period, the volunteer instills 1 to 3 drops of the ophthalmic composition at a frequency of 3 to 6 times a day. The effect of reducing the feeling of dryness by each of the ophthalmic compositions in the above was evaluated, and the evaluation of each ophthalmic composition was totaled. The results are shown in Tables 8 to 15 below. The following evaluation criteria were adopted.

◎◎: When the feeling of dryness caused by wearing contact lenses or VDT work was significantly reduced, and the percentage of volunteers who answered that the effect of reduction was sustained was 90% or more.

◎: When the feeling of dryness caused by wearing contact lenses or VDT work was remarkably reduced, and the proportion of volunteers who answered that the reduction effect was sustained was 70% or more and less than 90%.

場合: When the feeling of dryness due to wearing of contact lenses or VDT work is remarkably reduced, and the ratio of volunteers who answered that the reduction effect was sustained was 50% or more and less than 70%.

△: The dry feeling caused by wearing contact lenses or VDT work was reduced by the chopsticks, and the percentage of volunteers who answered that the reduction effect was sustained was less than 50%.

One lens compatibility test

The following test was conducted to examine the compatibility of the ophthalmic composition according to the present invention with contact lenses 1 "raw. First, a commercially available soft contact lens (Menicon Soft 7 manufactured by Mecon Corp.) 2. Prepare a plurality of lenses with a lens diameter of 13.5 mm), immerse them in a saline solution (ISO 10344 standard) maintained at a temperature of 25, and then In, the lens diameter of each contact lens was measured using a projector (a universal projector manufactured by Nicon Corporation), and the obtained measured value was recorded as the initial value of the lens diameter.

Next, the contact lens for which the initial value of the lens diameter was obtained as described above was : 1 <[\! Π

After immersing in the ophthalmic composition prepared as described above under a temperature condition of 25 ° C. for 3 days, while maintaining the immersion state, the lens diameter is projected in the same manner as described above. The operation of measuring with an instrument was performed on three contact lenses for each ophthalmic composition.

Then, the difference (d) between the measured value of the lens diameter (value after immersion) obtained in this way and the initial value of the lens diameter obtained earlier is expressed by the formula: d = value after immersion-initial value, Was calculated for each contact lens according to the formula, and the average of the calculated values was calculated for each ophthalmic composition. Here, it is needless to say that the smaller the value of the amount of change in the lens diameter, the better the suitability for the contact lens, and it is particularly desirable that the value of the amount of change in the lens diameter be within ± 0.2 mm. O

From the time on, while the ophthalmic composition having a lens diameter change value within ± 0.2 mm was regarded as “Pass”, a composition larger than ± 0.2 mm was evaluated as “Fail”, and Tables 8 to 15 also show those evaluations.

Example

13 14 15 16 17

Ν-Acetyl darcosamine 0.5 0.5 0.5 0.5 0.5 Hydroxypropyl methylcellulose 0.15

Hydroxyethenoresenolerose 0.15

Attachment

Heated / sodium relonate 0.15

Chondroitin sulfate sodium 0.5 edetate sodium 0.05 0.05 0.05 0.05 0.05 boric acid 0.5 0.5 0.5 0.5 0.5 w

Borax

Ά 0.05 0.05 0.05 0.05 0.05 Sorbic acid realm 0.15 0.1 0.1 0.1 0.1

NaCl 0.275 0.275 0.275 0.275

KC1 0.055 0.055 0.055 0.055 Dry feeling reduction sustained effect ◎◎ ◎◎ ◎◎ ◎◎ ◎◎

Lens compatibility Pass Pass Pass Pass Pass \]

9

o

00

O

0

Example

26 27 28 29 30 31

Ν-Acetyl darcosamine 0.5 0.5 0.5 0.5 0.5 0.5 Poloxamer 407 0.5 0.5 Tetronic 1107 0.5 0.5 Polysorbate 0.25

Attachment

Add Propylene Dariko 0.5

7 ° ρ pilmeti; Lurose 0.15 0.15 0.15 0.15

Hydroxicetinoresenorelose 0.15 0.15 Nedatumate edetate 0.05 0.05 0.05 0.05 0.05 0.05

W

Boric acid 0.5 0.5 0.5 0.5 0.5 0.5 Δ ° Borax 0.05 0.05 0.05 0,05 0.05 0.05

ΡΗΜΒ 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001

NaCl 0.275 0.275 0.275

KC1 0.055 0.055 0.055 0.017 0.055 Dry feeling reduction sustained effect ◎◎ © ◎ ◎◎ ◎◎ ◎◎ ◎◎ Lens compatibility Pass Pass Pass Pass Pass Pass Table 11

. \

13

Comparative example

13 14 15 16 17 Head mouth Xip mouth Pinore Chinoresenore mouth 0.15

Hydrokische / Reseno-Rellose

One 0.15

Hia / Sodium leronate 0.15 Addition Sodium conotroitin sulfate

% 0.5 medetate sodium 0.05 0.05 0.05 0.05 0.05

W boric acid 0.5 0.5 0.5 0.5 0.5

/

W Borax 0.05 0.05 0.05 0.05 0.05

力 Potassium sonolevate 0.15 0.1 0.1 0.1 0.1

NaCl 0.275 0.275 0.275 0.275 0.275

KC1 0.055 0.055 0,055 0.055 0.055 Dry feeling reduction sustained effect △ Δ Δ △ △ Lens compatibility Passed Passed Passed Passed

14

Comparative example

18 19 20 21 Poloxamer 407 0.5

Tetronic 1107 0.5

Polysonolate 0.25

Propylene Darico / Re 0.5

Hydroxip mouth pill methyl senorellose 0.15 0.15 0.15 0.15

ニ Disodium detoate 0.05 0.05 0.05 0.05

Boric acid 0.5 0.5 0.5 0.5

W Borax 0.05 0.05 0.05 0.05

Δ ° Potassium sozolevate 0.1 0.1 0.1 0.1

NaCl 0.275 0.275 0.275 0.085

KC1 0.055 0.055 0.055 0.017 Dry feeling reduction effect △ △ Δ Δ Lens compatibility Pass Pass Pass Pass Five

As is evident from the results of Tables 8 to 15, the ophthalmic compositions according to the Examples containing N-acetyldarcosamine do not contain N-acetyldarcosamine. It is recognized that the dry feeling can be effectively reduced as compared with the ophthalmic composition according to the comparative example.

In addition, in the ophthalmic composition according to the example containing N-acetyldarcosamine, the shape (diameter) of the contact lens is the same as the ophthalmic composition according to the comparative example that does not contain N-acetyltilcosamine. From this, it is recognized that the composition does not affect the eye drops, and it can be understood from this that the ophthalmic composition of the present invention has excellent suitability for contact lenses. Therefore, such an ophthalmic composition can be used with or without wearing a contact lens.

As is apparent from the above description, in the ophthalmic composition according to the present invention, at least one kind of a specific amino sugar derivative that is safe for a living body is contained in an aqueous medium. However, there is no danger of adverse effects on the living body even if used for a long period of time. VDT work, etc., which overuses the eyes. Various symptoms such as a feeling of dryness can be advantageously reduced, and such a reduction effect can be maintained for a long time. Further, since the ophthalmic composition does not adversely affect the contact lens, it can be used either when the contact lens is worn or when the contact lens is not worn. If eye drops are applied when wearing the lens, the feeling of wearing the contact lens can be advantageously improved.

Claims

O 2004/082673 41 Scope of request

1. An ophthalmic liquid composition characterized in that a permanent medium contains at least one of the amino compounds represented by the following general formulas (I) and (II). object.

Wherein, X ¹ and X ² are each independently a hydrogen atom, 1 to the number of carbon atoms: the hydrocarbon group of L 8, one - shows an - ^1, or one CH _2. However, R,

O 0

Represents one OH, one ONa, -OK, or a hydrocarbon group having 1 to 18 carbon atoms. 1

[Wherein, X ³ and X ⁴ each independently represent a hydrogen atom, a hydrocarbon group having 1 to 18 carbon atoms, —CR ² , or —CH ₂ ——R ² ^. Where R ² is

O O

— OH, — ONa, —OK, or C1-C4; represents a hydrocarbon group with L8. ]

2. The ophthalmic liquid composition according to claim 1, wherein the amino sugar derivative represented by the general formula (I) is a glucamine represented by the following general formula (m) or an attractant thereof. O 2004/082673

42

[Where, ^^ and ぴ? ^ Independently represents a hydrogen atom, a hydrocarbon group having 1 to 18 carbon atoms, 1 — ¹ , or 1 CH ₂ —C—R ¹ . Where R ¹ is

o &

Represents one OH, -ONa, -OK, or a hydrocarbon group having 1 to 18 carbon atoms. 1

3. The amino sugar derivative represented by the general formula (Π) is dalcosamine or a derivative thereof represented by the following general formula (IV) or galactosamine or a derivative thereof represented by the following general formula (V). 2. The ophthalmic solution composition according to claim 1.

[Wherein, ³ and ⁴ each independently represent a hydrogen atom, a hydrocarbon group having 1 to 18 carbon atoms, —R ² , or one CH ₂ —one R ² . Where R ² is

0 0

Represents one OH, one ON &, —OK., Or a hydrocarbon group having 1 to 18 carbon atoms. ]

Wherein, ¾ ³及Pi ⁴ are each independently, MizuHata atom, SumiHata number 1-18 of hydrocarbon HataHajime, - - R ^2, or one CH ₂ - C-shows a R ^2. Where R ² is

0 o

1 OH, —ONa, —OK, or a hydrocarbon group having 1 to 18 carbon atoms. ]

4. The method according to claim 2, wherein the dalcamine represented by the general formula (m) or a derivative thereof is N-methyl-D (I) -glucamine or N-alkyl-N-methyl-D-glucamine. Ophthalmic solution composition.

5. The ophthalmic solution composition according to claim 3, wherein the dalcosamine represented by the general formula (IV) or a derivative thereof is N-acetyltilcosamine or glucosamine.

6. The ophthalmic solution composition according to claim 3, wherein the galactosamine represented by the general formula (V) or a derivative thereof is N-acetylacetylgalactosamine or galactosamine.

7-The ophthalmic liquid composition according to any one of claims 1 to 6, wherein the aminosugar derivative is contained in a ratio of 0.001 to 10 wZw%. object.

8. The ophthalmic solution composition according to any one of claims 1 to 7, further comprising boric acid or a salt thereof.

9. The ophthalmic liquid composition according to claim 8, wherein the amino derivative and the boric acid or a salt thereof are contained in a molar ratio of 1: 100 to 100: 1. object.

10. The ophthalmic liquid composition according to claim 8 or 9, wherein the boric acid or a salt thereof is contained in a ratio of 0.0001 to 10. 10. .

1 1. Preservatives, bactericides, chelating agents, tonicity agents, buffers, thickeners, surfactants, anti-inflammatory agents, decongestants, antiallergic agents, fresheners, flavoring agents, vitamins The ophthalmic solution composition according to any one of claims 1 to 10, further comprising at least one of the following amino acids.

12. The ophthalmic liquid composition according to any one of claims 1 to 11, which is used as a liquid composition for contact lenses.

13. The ophthalmic solution a composition according to any one of claims 1 to 11, which is used as an ophthalmic composition.