WO2005002595A1

WO2005002595A1 - Ophthalmic composition

Info

Publication number: WO2005002595A1
Application number: PCT/JP2004/008739
Authority: WO
Inventors: Sadayasu Tanikawa; Sayuri Fukuchi
Original assignee: Menicon Co., Ltd.
Priority date: 2003-07-03
Filing date: 2004-06-22
Publication date: 2005-01-13
Also published as: JPWO2005002595A1; JP4850513B2

Abstract

An ophthalmic composition that not only can effectively heal the symptoms of dry eyes for a prolonged period of time but also at the wearing of contact lens, can effectively inhibit the protein attachment to and accumulation on the lens so as to realize magnificent availability. In particular, an ophthalmic composition comprising a water base medium and, contained therein as indispensable components, a combination of at least one compound selected from the group consisting of alginic acid and/or a salt thereof, gellan gum and pectin and a nonionic surfactant, the ophthalmic composition having its tonicity adjusted so as to range from 0.5 to less than 0.9 w/v% in terms of sodium chloride.

Description

Specification

Ophthalmic composition

Technical field

The present invention relates to an ophthalmic composition, and particularly to an ophthalmic composition that can advantageously prevent protein adhesion when wearing a contact lens and effectively improve the symptoms of dry eye. The present invention relates to a composition for use.

^ Scenic technology

[0002] As is well known, a contact lens being worn is always in a state where dirt easily adheres. There are mainly three types of stains that adhere to contact lenses: lipids, proteins, and microorganisms. Moreover, since the mainstream of soft contact lenses in recent years is ionic polymer soft contact lenses, the most problematic stain in such contact lenses is considered to be proteins. This is because the contact lens surface is negatively charged, while the proteins are positively charged, and their electrostatic interaction makes it easier for proteins to adhere to contact lenses. is there.

[0003] When dirt such as proteins accumulates on the contact lens, deterioration of the lens material and a feeling of wearing are caused, and furthermore, the accumulated dirt causes microbes such as bacteria and fungi. It is said that it can be a nutrient source. It is also known that the accumulation of dirt causes giant papillary conjunctivitis allergic conjunctivitis.

[0004] On the other hand, in recent years, the number of wearers of contact lenses has increased, and dry eyes have occurred due to the wearing of contact lenses for a long period of time. ), Etc., contact lens wearers are increasingly complaining of discomfort. Causes of such dryness and discomfort include proteins in the tears adhering to the extracontour lens during wear, and corneal epithelial damage due to increased osmotic pressure of the tears, etc. Is mentioned. However, conventional ophthalmic solutions are adjusted to the same osmotic pressure as tears, and applying such ophthalmic solutions does not effectively reduce the osmotic pressure of elevated tears. Not be able to get the effect on dry eye which has been increasing in recent years Was difficult. Even if the feeling of dryness can be reduced, it is only temporary, and by repeating the instillation, the tear component is washed away, resulting in dry eyes. This was causing a vicious cycle of doing.

[0005] Therefore, an ophthalmic solution that can prevent the protein from adhering to and accumulating on the contact lens and advantageously eliminate the symptoms of dry eye is desired not only by contact lens wearers but also by practitioners. It is rare.

[0006] In order to prevent protein from adhering to a contact lens, for example, Patent Document 1 discloses that although it is not an ophthalmic solution, citrate or the like is used as an active ingredient having an effect of preventing protein adhesion. A method for cleaning a contact lens using a cleaning solution containing is described. However, citrate has a strong negative charge and is relatively low in molecular weight, so it is highly cytotoxic and easily adsorbs to contact lenses. There is an inherent problem that eye damage is likely to occur. Further, even if such a solution containing citric acid as a detergent is instilled, the effect of shortening the residence time on the cornea cannot be sufficiently obtained.

[0007] Further, Patent Documents 2 and 3 propose a contact lens agent containing alginic acid or alginic acid, and it is clear that the alginic acid and the like improve the cleaning properties and make it difficult for protein stains to adhere. Has been. However, these publications do not disclose any means for resolving the symptoms of dry eye.

[0008] Patent Document 1: Japanese Patent Publication No. Hei 8-503084

Patent Document 2: Japanese Patent Application Laid-Open No. 7-157747

Patent Document 3: Japanese Patent Application Laid-Open No. 2001-228445

Disclosure of the invention

Problems to be solved by the invention

[0009] Here, the present invention has been made in the background of vigorous circumstances, and a problem to be solved is that the symptoms of dry eye can be advantageously eliminated over a long period of time. At the same time, it is intended to provide an ophthalmic composition that effectively suppresses the attachment and accumulation of protein to a contact lens when the contact lens is worn, and realizes an excellent feeling in use. Means for solving the problem

[0010] The inventors of the present invention have conducted intensive studies to solve such problems, and as a result, have found that at least one of alginic acid, alginate, diurangam, and pectin has a nonionic property. By combining with a surfactant and adjusting the tonicity or the osmotic pressure so as to be lower than the tonicity or the osmotic pressure of ordinary tears, the symptoms of dry eye are advantageous for a long time. It has been found that it is possible to eliminate or alleviate the problem and to effectively prevent the generation of a foreign-body sensation due to the contact lens and the attachment of protein to the contact lens when the contact lens is worn.

[0011] Therefore, the present invention has been completed based on powerful knowledge, and a first aspect of the present invention is that alginic acid and / or a salt thereof, diperam gum, and alginic acid are contained in an aqueous medium. Pectin, comprising at least one or more compounds selected from the group consisting of Pectin and a nonionic surfactant, and having a tonicity of 0.5 w / v% or more, calculated as An ophthalmic composition comprising less than 9 w / v%.

[0012] According to a second aspect of the ophthalmic composition according to the present invention, at least one compound selected from the group consisting of alginic acid and / or a salt thereof, dielan gum, and pectin comprises: 001w / w%-10. Ow / w.

[0013] Further, according to a third aspect of the present invention, the nonionic surfactant is contained at a ratio of 0.1 Olw / w% -5.OwZw%.

According to the fourth aspect of the present invention, a polyoxyethylene-polyoxypropylene block copolymer or polyoxyethylene sorbitan monoolate can be suitably used as the nonionic surfactant. .

[0015] According to a fifth aspect of the ophthalmic composition according to the present invention, the hydroxypropylmethylcellulose power S is preferably further contained.

Further, according to a sixth desirable aspect of the present invention, the hydroxypropylmethyl cellulose is contained in a ratio of 0.01 w / w% -5.Ow / w%.

According to a seventh embodiment of the ophthalmic composition according to the present invention, the nonionic surfactant has a surface tension of 25 ° C. in an aqueous solution containing 0.1% w / w% of the nonionic surfactant. , 55 m 2, m or less will be suitably used. According to the eighth aspect of the ophthalmic composition according to the present invention, a preservative, a bactericide, a thickening agent, an osmotic pressure adjusting agent, a chelating agent, a refreshing agent, a surfactant (provided that , Non-ionic surfactants), at least one of anti-inflammatory, anti-allergic, amino acids and vitamins.

Further, according to a ninth aspect of the present invention, the above-described ophthalmic composition has a function of effectively suppressing protein attachment, and has an adverse effect on contact lenses. From the viewpoint that it is not particularly desirable, it is desirable to use it as an eye drop for a contact lens, particularly, an eye drop that is applied while wearing a contact lens. The invention's effect

That is, in the first embodiment of the present invention, at least one of alginic acid and / or a salt thereof, dielan gum, and pectin, which are anionic polysaccharides, is used. The charged protein is less likely to adhere to the contact lens being worn, which effectively prevents protein from adhering and accumulating. In addition, since these compounds are polymers, they do not adversely affect the physical properties and shape of the contact lens, which are difficult to be taken into the material of the contact lens.

[0021] Alginic acid and Z or a salt thereof, dilan gum, and pectin are characterized in that they are gelated (increased in viscosity) by cations such as Ca ²⁺ ions in tear fluid. Due to the increase in viscosity (increase in viscosity), the residence time on the cornea after instillation is prolonged, and the effect of the ophthalmic composition according to the present invention is maintained for a long time. Therefore, for example, when a drug is blended in the ophthalmic composition according to the present invention, there is also obtained an advantage that the drug stays on the cornea and the contact time becomes longer.

[0022] Moreover, at least one compound of alginic acid and / or a salt thereof, diperam gum and pectin is used in combination with a nonionic surfactant, so that the By the interaction, at least one compound of alginic acid and / or a salt thereof, dielan gum, and pectin, which play a role in protecting the mucin layer, can be uniformly distributed throughout the cornea and conjunctiva. For this reason, uniform gelling can be performed without causing unevenness, and after instillation, a uniform gel-like film is formed on the regular surface. This does not lead to unstable vision due to unevenness. Symptoms such as dry feeling and discomfort can be advantageously eliminated. Note that tear fluid has a three-layer structure consisting of a mucin layer, an aqueous layer, and an oil layer in order from the corneal side.Especially if the mucin layer affects the dryness of the eyes and the occurrence of eye disease ,It is said.

The composition for eye drops according to the present invention has a tonicity (osmotic pressure) of normal tear fluid, ie, 0.9 wZv% (about 285 m〇smZkg in terms of sodium salt) in terms of sodium chloride. ), The osmotic pressure of tears raised by dry eye is appropriately reduced, and the dry feeling is advantageously reduced.

[0024] As a result, in the ophthalmic composition according to the present invention, the symptoms of dry eye can be extremely effectively eliminated over a long period of time, and therefore, it is much better than before. This gives the user a feeling of use. In addition, when a contact lens is worn, adhesion and accumulation of proteins on the contact lens can be advantageously suppressed.

[0025] Further, in the second and third aspects of the present invention, the effect of each component is effectively realized.

[0026] Furthermore, in the fourth embodiment of the present invention, polyoxyethylene-polyoxypropylene block copolymer or polyoxyethylene sorbitan monoolate, which has extremely low eye irritation and a very low possibility of adsorption to a contact lens. As a result, safety is further enhanced.

[0027] In addition, according to the fifth aspect of the present invention, when hydroxypropyl methylcellulose is contained, the wettability and the moisturizing property are advantageously improved by the thickening action, and the effect of moisturizing the eyes is obtained. At the same time, the effect of the active ingredient of the ophthalmic composition is further maintained, so that a more excellent feeling in use is realized. In addition, the surface active action of hydroxypropylmethylcellulose is also exerted, so that more uniform gelling can be realized and the cleaning effect can be advantageously obtained. Further, in the sixth aspect of the present invention, the effect of hydroxypyrumethylcellulose is effectively realized.

[0028] In the seventh aspect of the present invention, the effect of the nonionic surfactant is more effectively exhibited.

[0029] Further, in the eighth embodiment of the present invention, a further function corresponding to the component to be contained is added to the ophthalmic composition. In a ninth aspect of the present invention, when used as an ophthalmic solution for a contact lens, the contact lens may be formulated with at least one compound of alginic acid and / or a salt thereof, diperam gum, and pectin. The effect of preventing protein adhesion is also exhibited, and the function of the ophthalmic composition according to the present invention can be maximized.

BEST MODE FOR CARRYING OUT THE INVENTION

[0031] By the way, the powerful ophthalmic composition according to the present invention mainly comprises an aqueous medium, and comprises (A) alginic acid and / or a salt thereof, diperam gum, and vectin as essential components. At least one compound selected from the group and (B) a nonionic surfactant are contained in combination, and the tonicity is adjusted to a specific value. It has a great feature in that it is adjusted to be lower than the teariness of tears.

[0032] More specifically, the ophthalmic composition according to the present invention has a tonicity (osmotic pressure) of 0.5 w / v% or more and less than 0.9 w / v% in terms of sodium chloride. In other words, in other words, the sodium chloride concentration is adjusted to be the same as the tonicity of the aqueous sodium chloride solution in the range of 0.5 w / v% or more and less than 0.9 w / v%. . Thus, by instilling an ophthalmic composition having a tonicity lower than the normal tonicity of tears (0.9 w / v% in terms of sodium salt), the tears due to dry eye The increase in tonicity is advantageously improved, so that dry feeling and discomfort are effectively reduced, and excellent feeling of use is obtained. The tonicity is 0.5w in terms of sodium chloride. If it is less than 10%, the tonicity is too low, which may cause eye irritation. If it is 0.9w / v% or more, the effect of reducing the dryness of the eyes is low. Within the range as described above, it is more desirable to adjust to a tonicity of about 0.8 w / v% in terms of sodium chloride by adopting such a tonicity. Eye symptoms will be further improved.

By the way, among the A components used as an essential component in the present invention, alginic acid is a linear polysaccharide composed of two types of peronic acids, D-mannuronic acid and L-guluronic acid, and a salt thereof. Examples include sodium alginate, potassium alginate and the like. Gellan gum is composed of D-gnorecose, D-glucuronic acid, and L-rhamnose, which are produced outside the cells by aerobic fermentation using Pseudomonas elodea as a carbon source using glucose as a carbon source. It is a polysaccharide used as sugar. Furthermore, pectin is D-galataturonic acid A polysaccharide that is linearly linked by four bonds. As described above, alginic acid and / or its salt, diperam gum, and vectin are all anionic high molecular polysaccharides having a carboxyl group, and in the present invention, one or more of these are used. Is used by appropriately selecting two or more.

[0034] The powerful A component acts as a protein adhesion inhibitor. More specifically, since the above-mentioned A component has a larger negative charge than that of the contact lens material, the protein in the tear is attracted to the force and the A component, which allows Attachment and accumulation of protein stains on the contact lenses can be extremely effectively suppressed. In addition, since the component A is a high molecular compound, it does not adversely affect the physical properties and shape of the contact lens, which is difficult to be taken into the inside of the contact lens.

[0035] Alginic acid and Z or a salt thereof, dilan gum, and pectin all have a feature that they are partially ion-crosslinked by a cation such as Ca ²⁺ and gelled (increased viscosity). Therefore, in the present invention, the compound also functions as a gelling agent. That is, when an ophthalmic composition containing at least one compound of alginic acid and / or a salt thereof, dielan gum, and pectin is instilled, the ophthalmic composition is affected by calcium ions and the like present in tears. Gelation (high-viscosity dangling) occurs on the Kyular surface. The gelation (higher viscosity) advantageously increases the residence time of the ophthalmic composition.

[0036] Further, although the content of the above-mentioned component A is appropriately set, if the content is too small, gelation does not sufficiently occur in the ocular surface, and the effect due to gelation does not occur. Where it may not be possible to obtain it, on the contrary, if it is too much, eye irritation may be caused or gel formation may become too strong and visual acuity after instillation may become unstable. Therefore, it is desirable that the composition is contained in the ophthalmic composition preferably in the range of 0.001w / w% -10.Ow / w, more preferably 0.1lw / w% -5.Ow / w%. Les ,.

On the other hand, as the nonionic surfactant (B) used as another one of the essential components of the present invention, those which have high safety to the living body and are ophthalmically acceptable , Which Can be advantageously used, but low-molecular nonionic surfactants are easily incorporated into the contact lens, and high-molecular nonionic surfactants are therefore desirable. Les ,. Among these polymeric nonionic surfactants, in particular, the irritation to the eyes is extremely low, and the possibility of adsorption to contact lenses is lower and the reason is safer. One polyoxypropylene block copolymer or polyoxyethylene sorbitan monoolate (polysorbate 80) is particularly advantageously used.

[0038] By using such a B component, the A component that plays a role in protecting the mucin layer by interacting with the mucin layer, which is considered to affect the dry feeling of the eye, is added to the cornea and the conjunctiva as a whole. Can be uniformly distributed. As a result, a uniform gel-like film (gel layer) is formed on the spherical surface. In addition, since the uniform gel layer is formed in this manner, the symptoms of dryness and discomfort that do not cause visual instability such as image distortion can be advantageously eliminated.

In addition, when the contact lens is worn, the active ingredient of the ophthalmic composition is applied to the back side (base curve side) of the contact lens, that is, between the cornea and the contact lens, by a strong nonionic surfactant. , And also effectively removes greasy dirt attached to the cornea and the contact lens. Further, the water wettability of the contact lens surface is also improved, and the occurrence of various symptoms such as blurred eyes, fogging of the contact lens, and a feeling of foreign matter can be advantageously prevented.

[0040] Furthermore, there are various components having different surface tensions in the component B described above. Among them, an aqueous solution containing 0.1 lw / w% of a nonionic surfactant is particularly preferable. Those having a surface tension at 25 ° C of 55 mN / m or less, more preferably 50 mN / m or less, are suitably employed. This is because, if such a material having a surface tension of more than 55 mN / m is used, the desired effect cannot be sufficiently obtained due to the low surface activity. Although the lower limit is not particularly limited, since it is feared that the tear oil layer is destroyed, the lower limit should be 35 mNZm or more. Specific examples of nonionic surfactants that achieve such a low surface tension include, for example, commercially available pull-mouth nicks, punorelonic R, tetronic, tetronic R (Germany) : BASF), specifically, Poloxamer 18 8.Poloxamer 237, Poloxamer 338, Poloxamer 407, Tetronic 704, Tetronic 904, Tetronic 908, Tetronic 1107, Tetronic 1304, Polysonoreceptor 80, and various other commercially available products. One or more of them can be appropriately selected and used.

[0041] Further, as the content of the component B, if the content is too small, it may not be possible to form a uniform gel layer at the time of gelling the component A on the molecular surface. On the other hand, if the amount is too large, it may cause eye irritation or cause a problem in eye safety such as an influence on contact lens standards. 01w / w%-5.0w / w%, more preferably 0.05 w / w%-1.0wZw% is desirable.

[0042] By the way, in the ophthalmic composition according to the present invention, when (C) hydroxypropylmethylcellulose is further contained in addition to the above-mentioned component A and component B, wettability and moisturizing effect are obtained due to its thickening action. The properties are advantageously improved, the eyes are moistened, and the effects of the active ingredients of the ophthalmic composition are further maintained, so that a more excellent feeling of use is obtained. In addition, due to the surfactant effect of hydroxypropyl methylcellulose, uniform gelling and washing effects can be obtained. In addition, as such a C component, any one that has high safety to a living body and is ophthalmically acceptable and has no influence on the shape and physical properties of a contact lens is advantageous. Can be used.

When the content of the component C is too small, the effect of the addition cannot be sufficiently obtained, and when the content is too large, the viscosity of the ophthalmic composition becomes too high and the feeling of use becomes poor. From the viewpoint of lowering, it is desirable to set within the range of 0.01 w / w%-5.0 w / w%, more preferably 0.05 w / w% -l. 0 w / w% .

[0044] Thus, the ophthalmic composition according to the present invention may further comprise, if necessary, one of various additive components used in general eye drops, in addition to the components described above. There is no problem even if two or more kinds are appropriately selected and added at a normal addition ratio. In addition, it is preferable that such added components have high safety to the living body and are sufficiently ophthalmologically acceptable and do not affect the shape or physical properties of the contact lens. Use within the quantitative range that meets those requirements Therefore, various functions according to the added components can be advantageously imparted to the ophthalmic composition without inhibiting the effect of the present invention at all.

[0045] For example, in order for the ophthalmic composition of the present invention to advantageously exhibit a disinfecting effect or a bactericidal effect on the eyes and contact lenses, and furthermore an antiseptic and preservative effect of the ophthalmic composition. An antiseptic or a bactericide having an antiseptic effect or a bactericidal effect is added. In general, such antiseptics and bactericides are desired to have an antiseptic or bactericidal effect and excellent compatibility with eyes and contact lenses, as well as those which are unlikely to cause allergies and other obstacles. Appropriate ones are selected from various types known for mackerel, and used alone or in combination.

[0046] Incidentally, the preservatives include, for example, sorbic acid, potassium sorbate, benzoic acid or a salt thereof, ethyl para-hydroxybenzoate, butyl para-oxybenzoate, propyl para-oxybenzoate, propyl para-benzoate, methyl chloro-benzoate, chloro acid Butanol, perborate such as perboric acid or sodium perborate, and the like. On the other hand, examples of the disinfectant include a biguanide disinfectant such as polyhexamethylene biguanide (PHMB) and a quaternary ammonium salt disinfectant such as polyquaternium. When such a preservative or bactericide is not used, the ophthalmic composition according to the present invention may be used as a single-use single-dose type, or disclosed in Japanese Patent Application Laid-Open No. 2002-80055. It is also possible to use as a multi-dose type using a discharge container with a filter as disclosed

[0047] In the ophthalmic composition according to the present invention, the viscosity can be adjusted by adding the above-mentioned component C, but a thickening agent or a thickener other than the component C is added. It is also possible. Examples of such a thickening agent or a thickening agent include various gums such as polysaccharides such as chondroitin sulfate, hyanolenoic acid, dalconic acid and salts thereof, mucopolysaccharides, and heteropolysaccharides. Synthetic organic polymer compounds such as polybutyl alcohol, poly-N-butylpyrrolidone, polyethylene glycol, polypropylene glycol, and polyacrylamide; hydroxyethinoresenorelose, canoleboxy methinoresenorelose, methinoresenolace mouth And the like; cellulose derivatives; and starch derivatives. [0048] Further, in the ophthalmic composition according to the present invention, an osmotic pressure adjusting agent is appropriately added so that the tonicity or the osmotic pressure has the above-mentioned values. The osmotic pressure adjusting agent used for adjusting the tonicity or the osmotic pressure includes sodium salt, potassium salt, sugars, sugar alcohols, polyhydric alcohols, ethers thereof, and esters thereof. At least one compound power S selected from the group will generally be used.

[0049] If the pH value of the ophthalmic composition is too high or too low, it may cause irritation to the eyes or cause eye damage. from where, usually, pH value of such ophthalmic compositions, the addition of such suitable _P H modifiers or buffering agents, 5. 3-8. 5 degree, be adjusted to about inter alia 7.0 Is desirable. As a pH adjuster used for such pH adjustment, sodium hydroxide, hydrochloric acid, or the like is used. As the buffering agent for keeping the safe range, a buffering agent is appropriately selected from conventionally known various agents and used. Specifically, for example, acids such as phosphoric acid, boric acid, carboxylic acid, and oxycarboxylic acid, and salts thereof (eg, sodium salt), and Good-Buffer

Force can also be mentioned because it can reduce the effect on contact lenses.

[0050] In addition, since calcium and the like may be deposited or adsorbed on a contact lens, particularly a soft contact lens, as dirt from tears, deposition or adsorption of such calcium or the like is generally performed. The ophthalmic composition for preventing blemishes can also be advantageously added with a clean H-dandrizing agent. Examples of such chelating agents include, for example, ethylenediaminetetraacetic acid (EDTA) and salts thereof, such as ethylenediaminetetraacetic acid disodium (EDTA-2Na) and ethylenediaminetetraacetic acid trisodium (EDTA '3Na). Can be

[0051] Further, in addition to the (B) nonionic surfactant as described above, the ophthalmic composition according to the present invention may contain a conventionally known anion-based surfactant at a concentration that does not impair the action and effect of the present invention. Surfactants, amphoteric surfactants, surfactants such as cationic surfactants, It may be added or contained.

[0052] Furthermore, menthol, borneol, camphor, geraniol, u-potash oil, bergamot oil, wicket oil, for the purpose of giving a refreshing sensation at the time of instillation and eliminating foreign body itchiness when wearing a contact lens. It is also possible to add a cooling agent such as heart oil, rose oil or cool mint.

[0053] In addition, the ophthalmic composition according to the present invention includes glycyrrhizic acid and salts thereof, ε-aminocaproic acid, allantoin in order to suppress inflammation in the eye caused by stress, wearing of contact lenses, and the like. , An anti-inflammatory agent such as sodium azulene sulfonate, vitamin B (including retinol palmitate, j3-carotene, etc.), vitamin B

2, B

6, B12, Vitamin E such as d-hydroxytocopherol acetate, vitamins such as panthenol, anti-allergic agents such as cromoglycic acid, sodium cromoglycate, tranilast, potassium dimilorast, aspartic acid and salts thereof Various additional components of amino acids such as aminoethylsulfonic acid, arginine, alanine, lysine, and gnoretamic acid can be appropriately added according to the intended use of the ophthalmic composition.

By the way, the powerful ophthalmic 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. Aqueous media used for this purpose are not only water itself such as tap water, purified water, and distilled water, but also a water-based solution that is highly safe for living organisms and is ophthalmological. It goes without saying that any of these can be used as long as they are sufficiently acceptable.

In preparing the ophthalmic composition according to the present invention containing the above-mentioned components, no special method is required, and the aqueous medium is prepared in the same manner as in the case of preparing an ordinary aqueous solution. It can be easily obtained by dissolving each component in

[0056] Then, when the eye drop composition according to the present invention obtained as described above is prescribed for eyes having symptoms such as dry eye, the same as conventionally known eye drops or eye drops is used. Then, an appropriate amount may be dropped. Then, when the ophthalmic composition according to the present invention is applied to the eye, gelation (high viscosity) occurs due to calcium ions and the like in tears, and the ozone is oxidized. On the Yular surface, a uniform gel layer can be formed, and the osmotic pressure of tears is appropriately adjusted. As a result, the discomfort and dryness of the eyes are extremely effectively improved, the symptoms of dry eye can be advantageously eliminated, and an excellent feeling in use can be realized. Since the ophthalmic composition according to the present invention does not have any adverse effect on the contact lens, it does not matter whether or not the contact lens is worn when instilling. In particular, if the eye drops are applied when wearing a contact lens, the active ingredient also penetrates and penetrates into the back side of the contact lens, realizing an excellent feeling of wearing the contact lens, and extremely adhering proteins to the contact lens. It can be prevented so that the function of the ophthalmic composition according to the invention is maximized.

When a powerful ophthalmic composition is used as an ophthalmic solution for a contact lens, the type of the target contact lens is not limited at all. Soft contact lenses and hard contact lenses that are classified into all types, such as water-containing and high water-containing, can be targeted, and there is no question whatsoever when applying the present invention.

Example

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

[0059] First, by adding predetermined additives to sterilized purified water at various ratios shown in Tables 1 and 2 below, various ophthalmic compositions having a pH of about 7.3 ( Example 111 and Comparative Example 118) were respectively prepared. In preparing the ophthalmic composition, poloxamer 407 (manufactured by BASF) or polysorbate 80 (manufactured by Nikko Chemicals) is used as a nonionic surfactant, while sodium alginate is used as an anionic polysaccharide. (Kimiki Algin, manufactured by Kimiki Co., Ltd.), Jielan Gum (manufactured by Sanshin Co., Ltd.) Kenolecogel AFT) or Vectin (a reagent manufactured by Wako Pure Chemical Industries, Ltd.) was used. In addition, sodium chloride, potassium salt, and propylene glycol are used as osmotic pressure adjusting agents, and hydroxypropyl methylcellulose (Metrose 60SH-4000 manufactured by Shin-Etsu Chemical Co., Ltd.) is used as a thickening agent. Reply In addition, boric acid and borax are used as buffers, disodium edetate is used as a chelating agent, 1-menthol is used as a cooling agent, and potassium sorbate is used as a preservative. Each was used as appropriate. Then, the pH and osmotic pressure of each of the obtained ophthalmic compositions were measured, and the obtained results are shown in Tables 1 and 2 below. A sex evaluation test was performed.

[0060] <Dry feeling reduction effect test>

For a total of 30 volunteers consisting of 10 oxygen-permeable hard contact lens wearers, 10 soft contact lens wearers, and 10 VDT workers who do not wear contact lenses, A sensory test was performed. Specifically, during a continuous test period of one month, the volunteer instills 13 drops of the ophthalmic composition at a time 3 to 6 times a day. The effect of reducing the dry feeling of each of the ophthalmic compositions during the test period was evaluated, and the evaluation of each ophthalmic composition was tabulated. Then, the tabulated results were judged according to the following criteria, and the judgment results are shown in Tables 1 and 2 below.

◎: When the feeling of dryness when wearing contact lenses or VDT work is remarkably reduced, and the proportion of those who answered that the reduction effect was sustained is 75% or more.

△: When the feeling of dryness when wearing contact lenses or VDT work was remarkably reduced, and the proportion of those who answered that the reduction effect was sustained was 50% or more and less than 75%.

X: When dryness due to wearing of contact lenses or VDT work is remarkably reduced, and less than 50% of the respondents say that the reduction effect has continued.

[0061] <Usability test>

A sensory test was conducted for a total of 30 volunteers for one month in the same manner as the above dryness reduction effect test. The volunteers themselves evaluated the feeling of use of each ophthalmic composition during the test period, and totaled the evaluations for each ophthalmic composition. And collection The measured results were judged based on the following criteria, and the judgment results are shown in Tables 1 and 2 below. ◎: Notes after instillation L, if the percentage of people who are satisfied with the ground and vision is 75% or more

Δ: Notes after instillation L, the ground, and the percentage of people who were satisfied with the visual acuity were 50% or more and less than 75%.

X: Notes after instillation L, if the percentage of people who are satisfied with the ground and vision is less than 50%

[0062] <Tear wetting evaluation test>

Each ophthalmic composition was applied to 30 volunteers. Then, the corneal surface was observed with a slit lamp microscope, the tear breakup time (BUT) was measured, and the evaluation was performed according to the following evaluation criteria. The results were shown in Tables 1 and 2 below. It was shown to. More specifically, the volunteers blink several times after fluorescein staining, then instruct the eyelid to open, and after a complete blink, the time until the tear film of the corneal epithelium is first destroyed. Was measured using a cobalt filter.

：: BUT is 15 seconds or more.

△: BUT is 10 seconds or more and less than 15 seconds.

X: BUT is less than 10 seconds.

[0063] [Table 1]

Example

1 2 3 4 5 6 Re 7 Q. Low Hatatsu 7—407 0.20 0.20 0 20 n i n 0 20 n 20 Ω 90 0 on E'I *.

Alkyl acid 1 um 0.20 0.20 o i n 0 25 0 10

Sierra Power "M 005 o in

Hectin n m

Propylene Gericol 0.50 0.50 1.00 1.00 1.00 1.00%

MUMETROUS '60SH-4000 0.10 0.10

Mouth

—Boric acid 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50

W

/ Borax 0.055 0.055 0.055 0.055 0.055 0.055 0.055 0.055 0.055

W EDTA 2Na 0.01 0.01 0.01 0.01 0.01 0.01 0.01

% 0.01 0.01

NaCI 0.20 0.40 0.40 0.20 0.40 One--One

KCI 0.05 0.05 0.05 0.05 0.05

Bok Menthol 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 Potassium sorbate 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 Purified water * ¹ Tekinatsu m. M qs mm Tekijika MM qs qs pH 7.38 7.35 7.39 7.37 7.35 7.35 7.36 7.36 7.35 penetration Pressure [mOsm / kg] 259 256 255 261 258 250 263 263 267 Effect of reducing dry feeling ◎ ◎ ◎ ® ◎ ◎ ◎ © ◎ Results of usability survey ◎ ◎ ◎ ® ◎ ◎ ◎ ◎ Tear wetting ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎ ◎

* 1: quantum sufficit 100 (sufficient to make the total amount 100 w / w%)

[0065] As is clear from the results shown in Table 1 of the force, the ophthalmic composition according to Example 1-13 has a dry feeling-reducing effect, a usability test result, and tear wettability. ◎ This indicates that the symptoms of dry eye can be effectively improved and the feeling of use is excellent. On the other hand, from the results in Table 2, in the ophthalmic composition according to Comparative Examples 18 to 18, the dryness-reducing effect, the usability research result, and the tear wettability were X or Δ.

More specifically, even when the above-mentioned component (A) and component (B) are blended in the same amount, the dryness and the like of the examples in which the osmotic pressure is set low are advantageously reduced. In addition, when the component B is not blended, the effect of reducing the dry feeling is not good. Because of the difficulty in achieving uniform formation, fluctuations in visual acuity, blurring, and the like occurred, causing discomfort and poor usability.

As a contact lens, a one-day accuview (BC 9.0 / P-3.00 / Dia 14.2) manufactured by Johnson 'End' Johnson Co., Ltd. was prepared, and as an ophthalmic composition, Examples 1, 6, and 8 obtained above were used. The compositions for eye drops according to Comparative Examples 3 and 6 were prepared respectively.

[0068] Then, after the contact lens was immersed in about 100 ml of physiological saline for 1 hour, the contact lens was taken out from the physiological saline and lightly dried with commercially available paper. Then, each of the contact lenses taken out was immersed in 10 ml of the ophthalmic composition for 5 minutes for 5 minutes each. Next, the contact lens was removed from each ophthalmic composition and lightly dehydrated with commercially available paper.Then, a protein solution having the composition shown in Table 3 below (the FDA artificial tear fluid without lipids) was used. 2 times diluted solution). Then, the protein solution in which the contact lens was immersed was agitated with a stirrer, and 200 μl of the solution was added at regular intervals (20 minutes, 60 minutes, 120 minutes, and 150 minutes). After sampling, high-performance liquid chromatography analysis was performed, and changes over time in the amount of protein attached were examined. Table 4 below shows the amount of protein attached after 150 minutes.

[Table 3]

[Table 4] Lens 1 Late A Tona J's People, "Legiance" Lm ^| f'SffJl

Example 1 0.472

Example 6 0.501

Example 8 0.498

Comparative Example 3 0.886

Comparative Example 6 0.952 Force As is clear from the results in Table 4, in the contact lenses immersed in the ophthalmic compositions according to Examples 1 and 68 in which the A component was blended, the A component was blended. It can be seen that protein adhesion is advantageously suppressed as compared with those of Comparative Examples 3 and 6, which are not performed.

Claims

The scope of the claims

[1] An aqueous medium contains at least one compound selected from the group consisting of alginic acid and Z or a salt thereof, diperam gum and pectin, and a nonionic surfactant, and Is not less than 0.5 wZv% and less than 0.9 wZv% in terms of sodium salt.

[2] At least one compound selected from the group consisting of alginic acid and / or its salt, perilla gum, and pectin has a power of 0.001 w / w% to 10. Ow / w. Item 4. The ophthalmic composition according to Item 1.

3. The ophthalmic composition according to claim 1, wherein the nonionic surfactant is contained in a ratio of 0.01 w / w% to 5. Ow / w%.

4. The ophthalmic composition according to any one of claims 1 to 3, wherein the nonionic surfactant is a polyoxyethylene-polyoxypropylene block copolymer or polyoxyethylene sorbitan monoolate.

[5] The ophthalmic composition according to any one of claims 1 to 4, further comprising hydroxypropylmethylcellulose power S.

[6] The ophthalmic composition according to claim 5, which is contained at a ratio of 0.01w / w% to 5. OwZw% of the hydroxypropylmethylcellulose.

[7] The nonionic surfactant according to any one of claims 1 to 5, wherein the nonionic surfactant has a surface tension of not more than 55 mN / m at 25 ° C in a 0.1 lw / w% aqueous solution. Term

7. The ophthalmic composition according to any one of 6.

[8] preservatives, bactericides, thickeners, osmotic agents, chelating agents, fresheners, surfactants

8. The method according to claim 1, further comprising at least one of an anti-inflammatory agent, an anti-allergic agent, an amino acid, and a vitamin, excluding a nonionic surfactant. 3. The ophthalmic composition according to item 1.

[9] As eye drops for contact lenses, instilling eye drops while wearing contact lenses

The ophthalmic composition according to any one of claims 1 to 8, which is used.