WO2004082673A1 - Composition ophtalmique liquide - Google Patents

Composition ophtalmique liquide Download PDF

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Publication number
WO2004082673A1
WO2004082673A1 PCT/JP2004/002782 JP2004002782W WO2004082673A1 WO 2004082673 A1 WO2004082673 A1 WO 2004082673A1 JP 2004002782 W JP2004002782 W JP 2004002782W WO 2004082673 A1 WO2004082673 A1 WO 2004082673A1
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WIPO (PCT)
Prior art keywords
ophthalmic
composition according
general formula
derivative
represented
Prior art date
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PCT/JP2004/002782
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English (en)
Japanese (ja)
Inventor
Sadayasu Tanikawa
Akira Tsuzuki
Original Assignee
Menicon Co. Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Menicon Co. Ltd. filed Critical Menicon Co. Ltd.
Publication of WO2004082673A1 publication Critical patent/WO2004082673A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/04—Artificial tears; Irrigation solutions

Definitions

  • the present invention relates to an ophthalmic solution composition
  • 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.
  • 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.
  • 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.
  • 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.
  • a sterilizing solution for the contact lenses a cleaning solution, a preservative solution, a rinsing solution, etc.
  • a plurality of types of care are performed.
  • versatile liquids multi-purpose solution:] ⁇ P S
  • rinsing liquid and sterilizing liquid have been marketed overseas and in Japan.
  • 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.
  • P HMB polyhexamethylene biguanide
  • quaternary ammonium compounds represented by benzalkonium chloride and polyquatanium
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the present inventors have conventionally used contact lens sterilizing solutions, cleaning solutions, storage solutions, rinsing solutions, MPS, etc.
  • a specific amino sugar derivative 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.
  • 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.
  • 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 ( ⁇ ) in an aqueous medium.
  • An ophthalmic solution composition comprising at least one amino sugar derivative.
  • 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.
  • R2 is
  • the ophthalmic solution composition 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 ( ⁇ ) 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.
  • 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.
  • 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.
  • 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.
  • 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 ( ⁇ ), while the amino sugar derivative represented by the general formula ( ⁇ ) 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.
  • 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 .
  • R 1 is
  • 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 .
  • R 2 is
  • 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 .
  • R 2 is
  • 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;
  • the galactosamine represented by the general formula (V) or a derivative thereof N-acetylgalactosamine or galactosamine can be advantageously used.
  • the aminosugar derivative is contained in a ratio of 0.0001 to 10 wZw%.
  • a configuration in which boric acid or a salt thereof is further contained is suitably searched for.
  • 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.
  • 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.
  • 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%.
  • Preservatives Preservatives, fungicides, chelating agents, tonicity agents, buffers, thickeners, surfactants, anti-inflammatory agents, decongestants, antiallergic agents, fresheners, flavoring agents, vitamins and amino acids
  • 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.
  • 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.
  • 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.
  • the ophthalmic composition when 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 ( ⁇ ), 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.
  • 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.
  • 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.
  • 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 ( ⁇ ) 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.
  • 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.
  • CO- R 1, one CH 2 -CO-R 1, -CO -R 2, and R 1 ⁇ 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.
  • the amino sugar derivative represented by the general formula (I) and the general formula ( ⁇ ) has an asymmetric carbon atom. Multiple isomers exist from multiple places.
  • the compounds represented by the general formula (I) and the general formula ( ⁇ ) are not limited as long as they are compounds represented by the general formula (I).
  • the glucamine represented by the general formula ( ⁇ ) or a derivative thereof is preferably employed as the amino sugar derivative represented by the general formula ( ⁇ ), while the amino sugar derivative represented by the general formula ( ⁇ ) 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.
  • Darcosamine also called chitosamine
  • V galactosamine represented by the general formula (V) or a derivative thereof
  • N-methyl-D (-)-glucamine also called meglumine
  • N-alkyl-N-methyl-D -Glucamine glucamine
  • N-acetyl dalcosamine N-acetyl galactosamine, dalcosamine, and galactosamine
  • 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.
  • 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.
  • 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.
  • a specific amino sugar derivative 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.
  • additive components such as preservatives, bactericides, chelating agents, tonicity agents, buffers, thickeners, surfactants, anti-inflammatory agents, decongestants, antiallergic agents, fresheners, and flavors
  • preservatives such as preservatives, bactericides, chelating agents, tonicity agents, buffers, thickeners, surfactants, anti-inflammatory agents, decongestants, antiallergic agents, fresheners, and flavors
  • the ophthalmic solution preparation of the present invention 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.
  • 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.
  • 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
  • perborate such as sodium perborate, chlorine dioxide, stabilized chlorine dioxide and the like can be mentioned.
  • the bactericide include a biguanide bactericide and a quaternary ammonium salt bactericide. Such conventionally known ones can be appropriately selected and employed.
  • 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.
  • 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.
  • 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.
  • a specific amino sugar derivative represented by the general formula as described above is used in the liquid composition for contact lenses according to the present invention. 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.
  • 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.
  • a chelating agent will also be advantageously added to the ophthalmic solution composition.
  • chelating agents include ethylenediaminetetraacetic acid (EDTA) and salts thereof, such as ethylenediaminetetraacetic acid disodium (EDTA * 2Na) and ethylenediaminetetraacetic acid / 3 sodium (EDTA * 3Na).
  • EDTA ethylenediaminetetraacetic acid
  • salts thereof such as ethylenediaminetetraacetic acid disodium (EDTA * 2Na) and ethylenediaminetetraacetic acid / 3 sodium
  • Such a chelating agent is contained in a liquid within a quantitative range that does not inhibit the action * effect of the present invention.
  • 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.
  • 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.
  • boric acid such as boric acid, borax, ammonium borate or a salt thereof is preferably used.
  • 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.
  • 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 ( ⁇ ) as described above.
  • 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 ( ⁇ ) 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.
  • 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.
  • 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.
  • a tonicity agent 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.
  • the thickener examples 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • the ophthalmic composition according to the present invention 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,
  • 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.
  • 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.
  • 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.
  • MPS multipurpose liquid
  • ophthalmic composition such as an ophthalmic solution.
  • 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.
  • 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.
  • the type of the contact lens to be used is not limited at all.
  • 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.
  • 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.
  • an appropriate amount may be instilled in the same manner as conventionally known eye drops or eye drops.
  • 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.
  • 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.
  • symptoms such as discomfort and dryness can be effectively improved, and such a reduction effect is long. It can be played over time.
  • 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.
  • 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%.
  • 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 ⁇ ) 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.
  • Poloxamer 407 0.5 0.5 0.5
  • 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.
  • the liquid composition for contact lenses according to Examples 1 to 3 has excellent lens compatibility.
  • 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.
  • 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)
  • Table 2 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.
  • 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)
  • a dalcosamine derivative represented by the general formula (IV)
  • a nonionic surfactant polyxamer 407; manufactured by BASF
  • Viscous agents hydroxypropyl methylcellulose
  • chelating agents EDTA-2Na
  • buffers borax
  • tonicity agents sodium chloride, potassium chloride
  • PHMB fungicides
  • 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.
  • 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.
  • Example 6 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 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.
  • Poloxamer 407 0.5 0.5
  • 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%.
  • 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.
  • MPS multipurpose liquid
  • 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.
  • 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.
  • the lens was rinsed with each MPS, and the lens was worn without being rinsed with tap water or physiological saline.
  • ⁇ 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%.
  • ⁇ 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%.
  • 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.
  • the liquid lens compositions for contact lenses according to Examples 7 to 12 are all excellent in lens compatibility.
  • 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 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.
  • 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.
  • the advantage that the sterilizing ability of a bactericide such as a bigger bactericide can be extremely effectively improved can be enjoyed.
  • a high bactericidal effect can be advantageously obtained, and thus the safety for the living body can be further improved.
  • 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.
  • 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%.
  • 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.
  • surfactants examples 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.
  • 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.
  • PHMB polyhexamethylene biguanide
  • 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.
  • 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.
  • d value after immersion-initial value
  • 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.
  • 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.
  • 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.
  • a specific amino sugar derivative that is safe for a living body
  • 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.
  • 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.

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Abstract

L'invention porte sur une composition ophtalmique liquide qui assure à l'oeil une sécurité, empêche les lentilles de contact de boursoufler ou de rétrécir de sorte que leur taille ne soit pas modifiée, a une excellente compatibilité avec les lentilles, remédie à l'inconfort, à la sécheresse, etc., de l'oeil lorsqu'on porte des lentilles de contact ou lors d'opérations VDT, cette composition pouvant conserver avantageusement toutes ses propriétés. L'invention porte également sur l'amélioration réelle de l'effet bactéricide d'un bactéricide contenu dans la composition ophtalmique liquide précitée lorsqu'on utilise cette composition comme une composition liquide contenant un bactéricide pour lentilles de contact, et plus particulièrement, lorsqu'on l'utilise comme bactéricide liquide ou MPS pour lentilles de contact. On prépare la composition ophtalmique liquide en ajoutant au moins un dérivé de sucre amino spécifique dans un milieu aqueux.
PCT/JP2004/002782 2003-03-20 2004-03-04 Composition ophtalmique liquide WO2004082673A1 (fr)

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WO2017159585A1 (fr) * 2016-03-14 2017-09-21 参天製薬株式会社 Agent antiseptique contenant de la méglumine ou un sel correspondant

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JPH10287570A (ja) * 1997-04-09 1998-10-27 Seikagaku Kogyo Co Ltd 角膜障害症治癒促進剤
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JPH04211011A (ja) * 1990-02-14 1992-08-03 Alcon Lab Inc 局所投与用薬剤組成物
JPH05170643A (ja) * 1991-10-21 1993-07-09 Pola Chem Ind Inc 水性目薬及びその製造法
JPH07506377A (ja) * 1992-05-06 1995-07-13 アルコン　ラボラトリーズ，インコーポレイテッド 眼科用組成物におけるホウ酸塩−ポリオール複合体の使用
JPH11501615A (ja) * 1994-12-14 1999-02-09 ライフグループ エス ピー エー カンナビノイド末梢レセプターに選択的に作用するモノおよびビカルボン酸のアミノ酸あるいはグリコサミンとのアミド類
JPH10513165A (ja) * 1995-02-03 1998-12-15 バイヤースドルフ・アクチエンゲゼルシヤフト 抗接着性の有効成分
JPH09301866A (ja) * 1995-10-12 1997-11-25 Otsuka Pharmaceut Co Ltd 眼疾患治療剤
JPH10287570A (ja) * 1997-04-09 1998-10-27 Seikagaku Kogyo Co Ltd 角膜障害症治癒促進剤
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017159585A1 (fr) * 2016-03-14 2017-09-21 参天製薬株式会社 Agent antiseptique contenant de la méglumine ou un sel correspondant
JP2017165729A (ja) * 2016-03-14 2017-09-21 参天製薬株式会社 メグルミン又はその塩からなる防腐剤
KR20180121593A (ko) 2016-03-14 2018-11-07 산텐 세이야꾸 가부시키가이샤 메글루민 또는 그의 염을 포함하는 방부제
RU2745617C2 (ru) * 2016-03-14 2021-03-29 Сантен Фармасьютикал Ко., Лтд. Антисептическое средство, включающее меглюмин или его соль
US11324829B2 (en) 2016-03-14 2022-05-10 Santen Pharmaceutical Co., Ltd. Antiseptic agent comprising meglumine or salt thereof

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