WO2021107035A1 - Composition pharmaceutique pour lentille de contact souple - Google Patents
Composition pharmaceutique pour lentille de contact souple Download PDFInfo
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- WO2021107035A1 WO2021107035A1 PCT/JP2020/044070 JP2020044070W WO2021107035A1 WO 2021107035 A1 WO2021107035 A1 WO 2021107035A1 JP 2020044070 W JP2020044070 W JP 2020044070W WO 2021107035 A1 WO2021107035 A1 WO 2021107035A1
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- WIPO (PCT)
- Prior art keywords
- soft contact
- contact lenses
- less
- pharmaceutical composition
- lenses according
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 126
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- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- MCSINKKTEDDPNK-UHFFFAOYSA-N propyl propionate Chemical compound CCCOC(=O)CC MCSINKKTEDDPNK-UHFFFAOYSA-N 0.000 description 1
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- 108090000623 proteins and genes Proteins 0.000 description 1
- FYNROBRQIVCIQF-UHFFFAOYSA-N pyrrolo[3,2-b]pyrrole-5,6-dione Chemical compound C1=CN=C2C(=O)C(=O)N=C21 FYNROBRQIVCIQF-UHFFFAOYSA-N 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
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- 238000011160 research Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
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- 239000000725 suspension Substances 0.000 description 1
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- XFLNVMPCPRLYBE-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate;tetrahydrate Chemical compound O.O.O.O.[Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O XFLNVMPCPRLYBE-UHFFFAOYSA-J 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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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
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
-
- 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 a pharmaceutical composition for soft contact lenses in which adsorption of alkyldiaminoethylglycine to soft contact lenses is suppressed.
- Lacrimal gland is a mixture of lacrimal gland secretion secreted from the main lacrimal gland and substances secreted from four or more types of accessory lacrimal glands, and contains Na, K, Ca, Cl, etc. as inorganic components, and is an organic component. It contains glucose, ascorbic acid, citric acid, urea, ammonia, amino acids, proteins and the like. Although there are individual differences, the concentration of glucose contained in tears is about 0.001 to 0.01 w / v%. However, in aqueous ophthalmic solutions, glucose may be added as a nutritional component in a higher concentration than tears.
- the glucose concentration in the aqueous ophthalmic solution disclosed in Patent Documents 1 to 4 is about 0.1 w / v%.
- some bacteria metabolize glucose to produce pyruvic acid to obtain energy, and glucose may promote the growth of such bacteria. Therefore, it is common to add glucose at a concentration lower than that of tears, especially in aqueous ophthalmic solutions having a reduced content of preservatives and preservatives.
- Non-Patent Documents 1 to 5 describe that preservatives such as benzalkonium chloride damage cells and irritate the skin. Povidone iodine is the least toxic, and alkyldiaminoethylglycine is toxic. Has been shown to be moderate. Patent Documents 1 to 4 also disclose ophthalmic compositions containing alkyldiaminoethylglycine hydrochloride.
- An object of the present invention is to provide a pharmaceutical composition for soft contact lenses in which adsorption of alkyldiaminoethylglycine to soft contact lenses is suppressed.
- the present inventor has conducted extensive research to solve the above problems. As a result, when a low concentration of alkyldiaminoethylglycine hydrochloride is added to a pharmaceutical composition for soft contact lenses, alkyldiaminoethylglycine tends to be adsorbed particularly on soft contact lenses.
- the present invention has been completed by finding that such adsorption is suppressed.
- one aspect of the present invention will be shown.
- a pharmaceutical composition for soft contact lenses containing an alkyldiaminoethylglycine hydrochloride of 0.001 w / v% or more and 0.008 w / v% or less, and a metal chloride.
- the nonionic surfactant is selected from the group consisting of polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan mono-long chain fatty acid ester, mono-long chain fatty acid polyethylene glycol, and polyoxyethylene polyoxypropylene block copolymer.
- the pharmaceutical composition for soft contact lenses according to the above [14], wherein the polyoxyethylene hydrogenated castor oil is polyoxyethylene hydrogenated castor oil 60.
- a buffer selected from the group consisting of borate buffer, phosphate buffer, carbon dioxide buffer, citric acid buffer, acetate buffer, HEPES buffer, and MOPS buffer.
- the amino acid is one or more amino acids selected from the group consisting of taurine, glutamic acid, aspartic acid, glycine, alanine, arginine, lysine, ⁇ -aminobutyric acid, ⁇ -aminovaleric acid, and salts thereof.
- the pharmaceutical composition for soft contact lenses according to any one of the above [1] to [34] which has a pH of 5.0 or more and 8.5 or less.
- the pharmaceutical composition for soft contact lenses according to any one of the above [1] to [34] which has a pH of 5.5 or more and 8.0 or less.
- the pharmaceutical composition for soft contact lenses according to any one of the above [1] to [34] which has a pH of 6.5 or more and 7.5 or less.
- the pharmaceutical composition for soft contact lenses according to any one of the above [1] to [37] which further contains a monoterpene.
- Alkyldiaminoethylglycine hydrochloride of 0.001 w / v% or more and 0.005 w / v% or less, Metal chlorides of 0.5 w / v% or more and 1.0 w / v% or less, Glucose of 0.002w / v% or more and 0.008w / v% or less, Nonionic surfactants of 0.005 w / v% or more and 0.05 w / v% or less, Buffering agent of 0.1 w / v% or more and 2.0 w / v% or less, Viscous agent of 0.05 w / v% or more and 0.5 w / v% or less, Amino acids of 0.05 w / v% or more and 0.5 w / v% or less, Monoterpenes of 0.001 w / v% or more and 0.035 w / v% or or less
- the pharmaceutical composition for soft contact lenses according to any one of the above [1] to [48] which is an aqueous solution.
- the content of alkyldiaminoethylglycine hydrochloride in the pharmaceutical composition for soft contact lenses is 0.001 w / v% or more and 0.008 w / v% or less.
- the above-mentioned provisions [1] to [51] can be applied to the above-mentioned uses and methods.
- the pharmaceutical composition for soft contact lenses according to the present invention contains alkyldiaminoethylglycine hydrochloride, but the adsorption of alkyldiaminoethylglycine on soft contact lenses is suppressed.
- the cytotoxicity of alkyldiaminoethylglycine hydrochloride can be said to be relatively lower than that of benzalkonium chloride and the like.
- alkyldiaminoethylglycine hydrochloride when a relatively low concentration of alkyldiaminoethylglycine hydrochloride is added to a pharmaceutical composition for soft contact lenses, alkyldiaminoethylglycine tends to be adsorbed on the soft contact lens. Therefore, when the components that suppress such adsorption were examined, it was found that metal chloride was effective.
- the pharmaceutical composition for soft contact lenses according to the present invention contains an alkyldiaminoethylglycine hydrochloride of 0.001 w / v% or more and 0.008 w / v% or less, and a metal chloride.
- alkyldiaminoethylglycine may be abbreviated as "ADG” and soft contact lenses may be abbreviated as “SCL”.
- Alkyldiaminoethylglycine hydrochloride is a compound having the following chemical structure, and has been conventionally mainly used as a preservative component.
- R-NH- (CH 2) 2 -NH- (CH 2) 2 -NH-CH 2 -CO 2 H ⁇ HCl [In the formula, R represents an alkyl group of C 8 H 17 to C 16 H 33 , mainly C 12 H 25 and C 14 H 29 . ]
- the present inventor sets the blending amount of alkyldiaminoethylglycine hydrochloride in the pharmaceutical composition for soft contact lenses to 0.001 w / v% or more, 0. It was set relatively low at .008 w / v% or less. When the concentration is 0.001 w / v% or more, the antiseptic action is more reliably exhibited.
- the concentration is 0.008 w / v% or less, cytotoxicity and the like are more reliably suppressed, and the present inventor states that the lower the concentration of alkyldiaminoethylglycine hydrochloride, the more alkyl to soft contact lenses. It has been experimentally found that the adsorption rate of diaminoethylglycine is increased.
- the concentration is preferably 0.002 w / v% or more, preferably 0.005 w / v% or less, and more preferably 0.003 w / v% or less.
- metal chloride metal cations and chloride ion (Cl -) refers to salts with, in the present invention are formulated as a component for inhibiting the adsorption of alkyldiaminoethylglycine to soft contact lenses.
- the metal chloride include alkali metal chlorides such as sodium chloride and potassium chloride; Group 2 metal chlorides such as calcium chloride and magnesium chloride, and alkaline earth metal chlorides such as calcium chloride are preferable. Those that are soluble in water are preferable.
- “Soluble in water” means when the test object is made into fine particles that pass through a No. 100 (opening: 150 ⁇ m) sieve, then 1 g is placed in water and vigorously shaken at 20 ° C. every 5 minutes for 30 seconds. , It means that the amount of water required to dissolve within 30 minutes is less than 10 mL.
- the concentration of the metal chloride in the pharmaceutical composition for soft contact lenses may be appropriately adjusted within the range in which the above adsorption effect is effectively exhibited, and is, for example, 0.05 w / v% or more and 5.0 w / v% or less. can do. When the concentration is within the range, the adsorption effect is more reliably exhibited.
- the concentration is preferably 0.1 w / v% or more, more preferably 0.5 w / v% or more, preferably 2.0 w / v% or less, and more preferably 1.0 w / v% or less.
- metal chloride Only one type of metal chloride may be used, or two or more types may be used in combination. When two or more kinds of metal chlorides are used, the above concentration is the total concentration.
- Glucose is one of the aldohexoses represented by the formula C 6 H 12 O 6 , also called glucose, which naturally has D-glucose and is conjugated to the electron transport chain in animals with a respiratory system. A large amount of ATP is produced, and it is present in tears at about 0.001 w / v% or more and 0.01 w / v% or less.
- the pharmaceutical composition for soft contact lenses according to the present invention preferably contains glucose of 0.001 w / v% or more and 0.01 w / v% or less.
- the ratio is 0.001 w / v% or more, the adsorption suppressing effect of the metal chloride can be more reliably protected, and when the ratio is 0.01 w / v% or less, the eye drops are stable. The sex can be secured more reliably.
- the ratio is more preferably 0.002 w / v% or more, further preferably 0.004 w / v% or more, more preferably 0.008 w / v% or less, and more preferably 0.006 w / v% or less. More preferred.
- nonionic surfactant is a surfactant that does not dissociate into ions even when dissolved in water.
- a polyoxyethylene chain or a hydroxyl group acts as a hydrophilic group, and a long-chain alkyl group is hydrophobic. Is the basis.
- Nonionic surfactants contribute to the stability of eye drops.
- the nonionic surfactant one or more selected from the group consisting of polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan mono-long-chain fatty acid ester, mono-long-chain fatty acid polyethylene glycol, and polyoxyethylene polyoxypropylene block copolymer.
- Nonionic surfactants can be mentioned.
- Polyoxyethylene hydrogenated castor oil is a compound obtained by etherifying hardened castor oil with a polyoxyethylene chain.
- the number of moles of ethylene oxide added to the polyoxyethylene chain in the polyoxyethylene hydrogenated castor oil can be, for example, 5 or more and 100 or less.
- 10 or more or 20 or more is preferable, 30 or more is more preferable, 40 or more is further preferable, 90 or less is preferable, 80 or less is more preferable, and 70 or less is further preferable.
- polyoxyethylene hydrogenated castor oil polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 60 and the like can be used, and polyoxyethylene hydrogenated castor oil 60 is preferably used. be able to.
- the number after the polyoxyethylene hydrogenated castor oil represents the number of moles of ethylene oxide added.
- Polyoxyethylene sorbitan monolong-chain fatty acid ester also called polysorbate, is a sorbitan fatty acid obtained by condensing ethylene oxide with sorbitan long-chain fatty acid ester produced by heating and reacting sorbitol and long-chain fatty acid under an alkali catalyst. It is an ester polyoxyethylene ether. Usually, a total of 18 or more molecules and 22 or less ethylene oxides are bound to each molecule. The carbon number of a long-chain fatty acid is generally 10 or more and 20 or less, and examples of the long-chain fatty acid include lauric acid, palmitic acid, stearic acid, and oleic acid.
- polyoxyethylene sorbitan monolong-chain fatty acid ester for example, polysorbate 20, polysorbate 60, polysorbate 65, and polysorbate 80 can be used, and polysorbate 80 is preferable.
- Mono long-chain fatty acid polyethylene glycol is an ester of long-chain fatty acid and polyethylene glycol, and stearic acid is mentioned as a long-chain fatty acid, and the degree of polymerization of polyethylene glycol is about 10 or more and about 60 or less.
- polyoxyl 40 stearate is preferable.
- Polyoxyethylene polyoxypropylene block copolymer is a copolymer of propylene oxide and ethylene oxide.
- Examples of the polyoxyethylene polyoxypropylene block copolymer include polyoxyethylene (160) polyoxypropylene (30) glycol (poloxamer 188), polyoxyethylene (196) polyoxypropylene (67) glycol (poloxamer 407), and poloxamer. 235 and the like can be mentioned.
- the concentration of the nonionic surfactant in the pharmaceutical composition may be appropriately adjusted, and can be, for example, 0.001 w / v% or more and 0.5 w / v% or less. When the concentration is within the above range, the stabilizing effect of the pharmaceutical composition is more reliably exhibited.
- the concentration is preferably 0.005 w / v% or more, more preferably 0.008 w / v% or more, preferably 0.1 w / v% or less, more preferably 0.05 w / v% or less, and 0. More preferably .02 w / v% or less.
- the "buffer” refers to a compound mainly for softening a change in pH due to an external substance, for example, a borate buffer, a phosphate buffer, a carbon dioxide buffer, a citric acid buffer, an acetate buffer, and a HEPES buffer.
- a borate buffer for example, a borate buffer, a phosphate buffer, a carbon dioxide buffer, a citric acid buffer, an acetate buffer, and a HEPES buffer.
- examples include one or more buffers selected from the group consisting of agents and MOPS buffers.
- a boric acid buffer is preferable, and boric acid and / or borax is more preferable. Boric acid and borax are also used as preservatives and also have a disinfecting effect on the conjunctival sac.
- the concentration of the buffer in the pharmaceutical composition for soft contact lenses may be appropriately adjusted, but can be, for example, 0.05 w / v% or more and 5.0 w / v% or less. When the concentration is within the range, the buffering action of the buffer is more reliably exerted.
- the concentration is preferably 0.1 w / v% or more, more preferably 0.5 w / v% or more, preferably 2.0 w / v% or less, and more preferably 1.0 w / v% or less.
- “Viscosity agent” increases the viscosity of pharmaceutical compositions for soft contact lenses, suppresses rapid evaporation of pharmaceutical compositions for soft contact lenses, improves liquid drainage, suppresses variations in the amount of drops, and has a feeling of use. It is an ingredient that contributes to improvement.
- glucose is also blended as an tonicity agent and a thickening agent, but in the present invention, glucose is used to assist the effect of metal chloride on the adsorption of alkyldiaminoethylglycine on soft contact lenses. Since it is blended as an ingredient, glucose is excluded from the category of thickeners in the present invention for convenience.
- the viscosity of the pharmaceutical composition for soft contact lenses according to the present invention may be appropriately adjusted, and may be, for example, 1.0 mPa ⁇ s or more and 200 mPa ⁇ s or less.
- the viscosity is preferably 50 mPa ⁇ s or less, preferably 30 mPa ⁇ s or less, more preferably 10 mPa ⁇ s or less, and even more preferably 3.0 mPa ⁇ s or less.
- thickener examples include hydroxypropyl methylcellulose, carboxyvinyl polymer, hydroxyethyl cellulose, methyl cellulose, alginic acid, polyvinyl alcohol, polyvinylpyrrolidone and the like, and hydroxypropyl methyl cellulose is preferable.
- the concentration of the thickener in the pharmaceutical composition for soft contact lenses may be appropriately adjusted, but can be, for example, 0.01 w / v% or more and 1.0 w / v% or less. When the concentration is within the above range, the above-mentioned action of the thickener is more reliably exhibited.
- the concentration is preferably 0.05 w / v% or more, more preferably 0.08 w / v% or more, preferably 0.5 w / v% or less, and more preferably 0.2 w / v% or less.
- Amino acid refers to a compound having an acidic group and an amino group such as a carboxy group or a sulfonic acid group (-SO 3 H) in the molecule is not limited to the 20 so-called proteinogenic amino acids.
- Amino acids mainly serve as nutrients for the eyes and contribute to the reduction of eyestrain.
- Amino acids include, for example, one or more amino acids selected from the group consisting of taurine, glutamic acid, aspartic acid, glycine, alanine, arginine, lysine, ⁇ -aminobutyric acid, ⁇ -aminobutyric acid, and salts thereof. ..
- the amino acid salt include alkali metal salts such as sodium salt and potassium salt.
- taurine is preferable. In addition to being a nutritional component, taurine is also said to have a metabolic promoting effect.
- the concentration of amino acids in the pharmaceutical composition for soft contact lenses may be appropriately adjusted, but can be, for example, 0.01 w / v% or more and 1.0 w / v% or less. When the concentration is within the range, the action of each amino acid is more reliably exerted.
- the concentration is preferably 0.05 w / v% or more, more preferably 0.08 w / v% or more, further preferably 0.1 w / v% or more, and preferably 0.5 w / v% or less. More preferably 0.2 w / v% or less.
- the pH of the pharmaceutical composition for soft contact lenses according to the present invention is adjusted to a range applicable to living organisms, especially eyes.
- the pH can be, for example, 5.0 or more and 8.5 or less, preferably 5.5 or more, more preferably 6.0 or more, still more preferably 6.5 or more, and 8.0 or more. The following is preferable, and 7.5 or less is more preferable.
- the pH of the pharmaceutical composition for soft contact lenses may be adjusted with the above-mentioned buffer or a pH adjuster.
- the pH adjuster is not particularly limited as long as it is applicable to living organisms, especially to the eyes, but for example, inorganic acids such as hydrochloric acid and boric acid; organic acids such as acetic acid, glutamic acid and aspartic acid; sodium hydroxide and sodium carbonate. , Inorganic bases such as sodium hydrogen carbonate; organic bases such as triethanolamine and monoethanolamine.
- the type and amount of the pH adjuster may be determined according to the pH to be adjusted in the pharmaceutical composition for soft contact lenses.
- the "monoterpene” is a compound composed of two isoprene units and having a molecular formula of C 10 H 16 , and in the present invention, a monoterpene monoterpene that mainly exhibits a cooling action is used.
- monoterpenes include one or more monoterpenes selected from the group consisting of menthol, camphor, and borneol.
- menthol either l-menthol or dl-menthol can be used, but l-menthol is preferable.
- camphor and borneol both d-form and dl-form can be used, but d-form is preferable.
- the concentration of monoterpene in the pharmaceutical composition for soft contact lenses may be appropriately adjusted, but can be, for example, 0.0005 w / v% or more and 0.1 w / v% or less. When the concentration is within the above range, an appropriate refreshing sensation can be obtained more reliably.
- the concentration is preferably 0.001 w / v% or more, more preferably 0.0015 w / v% or more, preferably 0.02 w / v% or less, and more preferably 0.01 w / v% or less.
- the "chelating agent” improves the stability of eye drops by blocking metal ions such as calcium ions and suppressing the formation of insoluble metal salts thereof.
- the chelating agent is not particularly limited as long as it is applicable to the living body, particularly to the eyes, and has such an action, and examples thereof include ethylenediaminetetraacetic acid (edetic acid), ascorbic acid, citric acid, and salts thereof. Be done.
- examples of the salt of ethylenediaminetetraacetic acid salt include ethylenediaminetetraacetic acid tetrasodium and ethylenediaminetetraacetic acid disodium.
- the concentration of the chelating agent in the pharmaceutical composition for soft contact lenses may be appropriately adjusted, and can be, for example, 0.001 w / v% or more and 0.2 w / v% or less. When the concentration is within the above range, the stabilizing effect of the chelating agent can be obtained more reliably.
- the concentration is preferably 0.002 w / v% or more, more preferably 0.005 w / v% or more, preferably 0.2 w / v% or less, more preferably 0.05 w / v% or less, and 0. More preferably, it is .02 w / v% or less.
- the pharmaceutical composition for soft contact lenses according to the present invention is not particularly limited as long as the effects of the present invention are not impaired, but a preservative or preservative other than alkyldiaminoethylglycine hydrochloride may be added.
- Preservatives or preservatives include, for example, benzalkonium chloride, benzalkonium bromide, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, chlorhexidine acetate, chlorobutanol, benzyl alcohol, phenethyl alcohol, sorbic acid or sorbic acid thereof.
- Examples thereof include salts, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, dehydroacetic acid or salts thereof, zinc chloride, polydronium chloride, thimerosal, dibutylhydroxytoluene, sodium chlorate, boric acid, boric acid and the like. These preservatives or preservatives may be used alone or in combination of two or more.
- Soft contact lenses are classified into 4 types by the FDA (US Food and Drug Administration). That is, Group I: Nonionic with a water content of less than 50%, Group II: Nonionic with a water content of 50% or more, Group III: Ionic with a water content of less than 50%. , Group IV: Classified as ionic with a water content of 50% or more, and among the constituent monomers of the raw material polymer, those having an anionic molar% of 1% or more are ionic and less than 1%. Is nonionic.
- the soft contact lens in the present disclosure may be any kind of the above soft contact lens, regardless of whether it is ionic or nonionic, water-containing or non-water-containing.
- soft contact lenses include, for example, 2-hydroxyethyl methacrylate (HEMA), EGDMA, SiMAA2, mPDMS1000, CE-PDMS, TRIS, EMA, methacryloyloxyethyl phosphorylcholine, TrisVC, MMA, MA, and the like.
- HEMA 2-hydroxyethyl methacrylate
- EGDMA EGDMA
- SiMAA2 mPDMS1000
- CE-PDMS mPDMS1000
- TRIS EMA
- methacryloyloxyethyl phosphorylcholine TrisVC
- MMA MMA
- MA methacryloyloxyethyl phosphorylcholine
- PEGMA Polyethylene glycol monomethacrylate
- GMA glycerol methacrylate
- DMA N, N-dimethylacrylamide
- VA vinyl alcohol
- NVP N-vinylpyrrolidone
- MAA methacrylic acid
- fluorine-based methacrylate examples thereof include system compounds, silicon-containing methacrylate compounds, silicone hydrogels, soft contact lenses containing cycloalkyl methacrylate and the like as main components.
- the soft contact lens in the present disclosure may be made of any of the above materials, but a soft contact lens containing 2-hydroxyethyl methacrylate (HEMA) as a main component is preferable, and 2-hydroxyethyl is more preferable.
- HEMA 2-hydroxyethyl methacrylate
- Examples thereof include soft contact lenses containing methacrylate (HEMA) and EGDMA as main components, or soft contact lenses containing HEMA and methacryloyloxyethyl phosphorylcholine as main components.
- the type of soft contact lens is not particularly limited, and can be used for any of disposable soft contact lenses, regular replacement soft contact lenses, conventional soft contact lenses, silicone hydrogel contact lenses, and color contact lenses.
- Silicone hydrogel contact lenses are contact lenses made of silicone hydrogel material.
- Colored contact lenses are also called colored contact lenses, and are colored for the purpose of beauty such as eye decoration and aesthetics.
- colored contact lenses are used to make the iris or corneal color region appear larger than when the contact lens is not worn, more specifically to color a region larger than the outer periphery of the iris or cornea.
- Contact lenses that have been colored in this way are sometimes called circle lenses.
- dyes such as inorganic dyes and organic dyes are used.
- pigments include azo pigments, phthalocyanine pigments, diketopyrrolopyrrole pigments, anthraquinone pigments, triphenodioxane pigments, biolantron pigments, isoindolin pigments, carbazole pigments, and quinoline pigments.
- Metal oxide pigments, carbon black and the like, and one type or a combination of two or more types can be used depending on the color and design of the color contact lens.
- even substances called pigments and dyes can be used by known means. Whether it is a soft contact lens that is not a color soft contact lens or a clear contact lens, it must be colored so light that it can be easily visually identified when immersed in a solution such as a cleaning solution. There is.
- the pharmaceutical composition for soft contact lenses according to the present invention can be produced by a conventional method.
- each component may be dissolved in water as a solvent.
- water such as distilled water, purified water, sterilized water, etc., which has impurities, bacteria, viruses, fungi, etc. less than the detection limit or sufficiently less than the detection limit is used.
- the container for accommodating the pharmaceutical composition for soft contact lenses of the present invention is not particularly limited as long as it is conventionally used as an eye drop container, and may be made of glass or plastic. Good.
- the constituent material of the plastic container is not particularly limited, and for example, polyethylene naphthalate, polyarylate, polyethylene terephthalate, polybutylene terephthalate, etc. , Polypropylene, polyethylene, any one of polyimide, or a mixture of two or more.
- the material of the container body that is, the member forming the accommodating portion for accommodating the pharmaceutical composition for soft contact lenses is polyethylene terephthalate or polypropylene. , Or polyethylene, more preferably polyethylene terephthalate.
- Inhibition of adsorption of alkyldiaminoethylglycine on soft contact lenses in the pharmaceutical composition for soft contact lenses according to the present invention is the softness of alkyldiaminoethylglycine contained in the pharmaceutical composition for soft contact lenses after immersion in the soft contact lens. It is evaluated that the adsorption rate to contact lenses is lower than the adsorption rate of alkyldiaminoethylglycine to soft contact lenses after immersion of a liquid having the same composition in soft contact lenses except that it does not contain metal chloride.
- the soft contact lens can be immersed, for example, by shaking the liquid in which the soft contact lens is immersed at 25 ° C. for 24 hours.
- the amount of alkyldiaminoethylglycine can be measured by, for example, the absorbance of wavelength light of a liquid obtained by reacting a color former such as Eosin Y with alkyldiaminoethylglycine, high performance liquid chromatography, or the like.
- the pharmaceutical composition for soft contact lenses according to the present invention assists tears and reduces discomfort, dry eyes, eyestrain, blurred vision, etc. when wearing soft contact lenses. It is valid.
- the pharmaceutical composition of the present invention can be used in either an internal or external form depending on the purpose. It can be provided as a topical liquid preparation for various purposes such as internal medicine as a form of internal medicine and ophthalmology, dentistry, otolaryngology, and dermatology as a form of external use. Especially preferably for ophthalmology.
- “Pharmaceutical composition for ophthalmology” means a pharmaceutical composition for ophthalmic use.
- the pharmaceutical composition include an aqueous liquid preparation containing water as a solvent.
- the "aqueous solution” means a liquid pharmaceutical composition containing water as a solvent.
- the aqueous liquid preparation can be prepared according to a conventional method such as dissolving or dispersing each component in water as a solvent, and may be a solution, a suspension or a milky lotion, but the aqueous liquid preparation which is a solution may be used. preferable.
- compositions for ophthalmology include eye drops (including eye drops that can be used while wearing soft contact lenses, also referred to as eye drops and eye drops), and eyewashes (while wearing soft contact lenses). Also includes eye drops that can also be used in the above, and also referred to as eye drops and eye drops), eye ointments, soft contact lens wearing solutions, soft contact lens care agents (cleaning solutions, preservative solutions, bactericidal solutions, disinfectants). Liquids ⁇ including multipurpose solutions ⁇ , etc.) are preferable, and are preferably eye drops, contact lens wearing liquids, eyewashes, or soft contact lens care agents, and particularly preferably eye drops.
- the pharmaceutical composition of the present invention contains eye drops that can be used while wearing soft contact lenses. That is, the pharmaceutical composition of the present invention can be applied to the eye while wearing soft contact lenses.
- the type of soft contact lens is not particularly limited, and can be used for any of disposable soft contact lenses, regular replacement soft contact lenses, conventional soft contact lenses, silicone hydrogel contact lenses, and color contact lenses. Silicone hydrogel contact lenses are contact lenses made of silicone hydrogel material.
- the dosage and administration of the eye drops of the present invention varies depending on the patient's symptoms, age, etc., but usually, it is sufficient to instill 1 or more, 6 times or less per day, 1 or more and 3 or less drops per day. ..
- the container used for the pharmaceutical composition of the present invention is sterilized according to a conventional method.
- the sterilization method is not particularly limited as long as it is a generally used method, and examples thereof include dry heat sterilization, electron beam sterilization, gamma ray sterilization, and ethylene gas sterilization.
- the sterilization process is electron beam sterilization.
- the present invention is a method for suppressing the adsorption of alkyldiaminoethylglycine on soft contact lenses, wherein the content of alkyldiaminoethylglycine hydrochloride in the pharmaceutical composition for soft contact lenses is 0.001 w / v% or more, 0. It also relates to a method characterized by blending a metal chloride with a pharmaceutical composition for soft contact lenses, which is 008 w / v% or less.
- the adsorption of alkyldiaminoethylglycine on soft contact lenses is further effectively suppressed by blending alkyldiaminoethylglycine hydrochloride, metal chloride and glucose in the pharmaceutical composition for soft contact lenses. ..
- the content of alkyldiaminoethylglycine hydrochloride in the pharmaceutical composition for soft contact lenses is limited to 0.001 w / v% or more and 0.008 w / v% or less in such a low concentration range. This is because the adsorption rate of alkyldiaminoethylglycine on soft contact lenses increases.
- the type and concentration of the pharmaceutical composition for soft contact lenses are used alone. Alternatively, they may be used in combination. The same applies to the pH and container of the pharmaceutical composition for soft contact lenses.
- Test Example 1 Adsorption test to soft contact lens Quantitative alkyldiaminoethylglycine hydrochloride solution (“Levon LAG-40” manufactured by Sanyo Kasei Kogyo Co., Ltd.) was diluted with purified water and mixed with boric acid (manufactured by Borax Francais). Borax (manufactured by Kosakai Pharmaceutical Co., Ltd.) was added, and the pH was adjusted to 7 with hydrochloric acid to prepare a solution having the composition shown in Table 1. The numerical value in the table is w / v%. Soft contact lenses belonging to Group I (“Seed 1day Fine UV plus” manufactured by Seed Co., Ltd.) were washed with purified water.
- the above aqueous solution (3 mL) was weighed into a vial, and one soft contact lens washed with purified water was immersed and shaken at 25 ° C. for 24 hours to prepare an SCL immersion liquid. Further, the aqueous solution in which the soft contact lens was not immersed was also shaken at 25 ° C. for 24 hours to prepare a control test solution. The above tests were conducted in 2 cases each.
- "ADG" represents alkyldiaminoethylglycine.
- the quantifying alkyldiaminoethylglycine hydrochloride solution (62.5 mg) was precisely weighed and water was added to make the total volume exactly 100 mL.
- This solution (2 mL) was precisely weighed and water was added to make the total volume exactly 20 mL, which was used as a standard solution.
- the SCL immersion solution and the standard solution 50 ⁇ L were precisely weighed, and the sum of the peak areas of alkyldiaminoethylglycine was determined by liquid chromatography under the following conditions.
- ADG hydrochloride content ( ⁇ g / mL) in SCL immersion solution or control test solution weighing amount (mg) of ADG hydrochloride solution for quantification x content of ADG hydrochloride solution for quantification (w / v%) / 100 / 1.03 / S s ⁇ S T
- 1.03 represents the density of the quantitative ADG hydrochloride solution (g / cm 3)
- S s represents the ADG peak area sum of the standard solution
- S T is in the SCL immersion liquid or control test liquid
- the sum of ADG peak areas is shown.
- the adsorption rate of ADG to soft contact lenses was calculated from the following formula. The results are shown in Table 1.
- Adsorption rate of ADG hydrochloride (%) 100-[(C TAV / C CAV ) x 100]
- C TAV indicates the average content of ADG in the SCL immersion solution ( ⁇ g / mL)
- CAV indicates the average content of ADG in the control test solution ( ⁇ g / mL).
- Test Example 2 Examination of material for soft contact lenses
- Example 1 is a preparation in which Reference Example 2 of Test Example 1 is used as Comparative Example 1 and 0.55 w / v% sodium chloride (manufactured by Manac Inc.) is added to Reference Example 2.
- SCL immersion liquids and control test liquids for each soft contact lens of groups I to IV shown in Table 2 were obtained. This test was carried out in 3 cases each. Groups I to IV are classified by the FDA (US Food and Drug Administration). Group I has a water content of less than 50% and is non-ionic, Group II has a water content of 50% or more and is non-ionic, and Group III.
- Group IV has a water content of 50% or more and is ionic.
- an alkyldiaminoethylglycine hydrochloride solution for quantification (“Levon LAG-40” manufactured by Sanyo Chemical Industries, Ltd.) (62.5 mg) was precisely weighed, and water was added to make the total volume exactly 100 mL.
- boric acid manufactured by Borax Francais
- borax manufactured by Kosakai Pharmaceutical Co., Ltd.
- Test Example 3 Effect of addition of glucose Under the same conditions as in Test Example 1, a formulation containing boric acid and borax in addition to alkyldiaminoethylglycine hydrochloride (Comparative Example 1), and sodium chloride or sodium chloride.
- a formulation containing boric acid and borax in addition to alkyldiaminoethylglycine hydrochloride (Comparative Example 1), and sodium chloride or sodium chloride.
- the preparations (Examples 1 to 3) having the composition shown in Table 3 containing borax (manufactured by Sanei Saccharification Co., Ltd.), the adsorption rate of alkyldiaminoethylglycine to the soft contact lens and the adsorption suppression rate to the preparation of Comparative Example 1 were determined. I asked. This test was carried out in two cases using "Seed 1day Fine UV plus" manufactured by Seed Co., Ltd. as a soft contact lens. The results are shown in Table 3.
- Test Example 4 Effect of addition of metal chloride other than sodium chloride Under the same conditions as in Test Example 1, potassium chloride (manufactured by Akaho Kasei Co., Ltd.) or calcium chloride (manufactured by Tomita Pharmaceutical Co., Ltd.) was used instead of sodium chloride or sodium chloride.
- potassium chloride manufactured by Akaho Kasei Co., Ltd.
- calcium chloride manufactured by Tomita Pharmaceutical Co., Ltd.
- Test Example 5 Examination of Sodium Chloride Concentration
- the adsorption rate of alkyldiaminoethylglycine on the soft contact lens and the alkyldiamino were used under the same conditions as in Test Example 1 using the formulation having the composition shown in Table 5 in which the sodium chloride concentration was changed.
- the adsorption suppression rate of the preparation of Comparative Example 1 containing only ethylglycine was determined. This test was carried out in two cases using "Seed 1day Fine UV plus" manufactured by Seed Co., Ltd. as a soft contact lens. The results are shown in Table 5.
- Test Example 6 Examination of Alkyldiaminoethylglycine Hydrochloride Concentration Alkyldiaminoethyl for soft contact lenses using a preparation having the composition shown in Table 6 in which the concentration of alkyldiaminoethylglycine hydrochloride was changed under the same conditions as in Test Example 1. The adsorption rate of glycine and the adsorption suppression rate for a preparation containing alkyldiaminoethylglycine at the same concentration without sodium chloride were determined. This test was carried out in 3 cases each using "Seed 1day Fine UV plus" manufactured by Seed Co., Ltd. as a soft contact lens. The results are shown in Table 6.
- Test Example 7 Confirmation of effect on colored soft contact lenses Colored soft contact made of the same material as "Seed 1day Fine UV plus” manufactured by Seed Co., Ltd. using the formulation shown in Table 7 under the same conditions as in Test Example 1. A formulation containing alkyldiaminoethylglycine at the same concentration as the adsorption rate of alkyldiaminoethylglycine with respect to the lenses "One Day Refrea Bijou” manufactured by From Eyes and "Trompleuil One Day” manufactured by Beaufrontia. The adsorption suppression rate for Comparative Example 4) was determined. This test was carried out in 3 cases each. The results are shown in Table 7.
- Test Example 8 Examination of pH Using the preparation having the composition shown in Table 8 in which the pH was adjusted with hydrochloric acid or an aqueous sodium hydroxide solution under the same conditions as in Test Example 1, the adsorption rate of alkyldiaminoethylglycine on the soft contact lens and the adsorption rate. The adsorption inhibition rate for the preparation containing no sodium chloride and the same concentration of alkyldiaminoethylglycine was determined. This test was carried out in 3 cases each using "Seed 1day Fine UV plus" manufactured by Seed Co., Ltd. as a soft contact lens. The results are shown in Table 8.
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Abstract
L'objectif de la présente invention est de fournir une composition pharmaceutique pour une lentille de contact souple, l'adsorption d'alkyldiaminoéthylglycine sur la lentille de contact souple étant supprimée. La composition pharmaceutique pour lentille de contact souple selon la présente invention contient : 0,001-0,008 % poids/vol. d'un chlorhydrate d'alkyldiaminoéthylglycine ; et un chlorure métallique.
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JPH0368503A (ja) * | 1989-08-08 | 1991-03-25 | Rohto Pharmaceut Co Ltd | コンタクトレンズ用液剤 |
JP2013032393A (ja) * | 2012-11-09 | 2013-02-14 | Rohto Pharmaceutical Co Ltd | 清涼化剤を含有するコンタクトレンズ用点眼剤 |
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MY181307A (en) * | 2014-02-06 | 2020-12-21 | Jsr Corp | Lens solution, contact lens, and production method therefor |
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JPH0368503A (ja) * | 1989-08-08 | 1991-03-25 | Rohto Pharmaceut Co Ltd | コンタクトレンズ用液剤 |
JP2013032393A (ja) * | 2012-11-09 | 2013-02-14 | Rohto Pharmaceutical Co Ltd | 清涼化剤を含有するコンタクトレンズ用点眼剤 |
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