Photostabilized formulation of aqueous atropine-containing pharmaceutical composition and photostabilization method therefor

Abstract

The present invention provides: an ophthalmic pharmaceutical formulation which exhibits excellent stability to light beams having specific wavelengths and in which an aqueous pharmaceutical composition containing atropine or a salt thereof at a concentration of 0.001-0.1% (w / v) is accommodated in a primary package which blocks light beams having wavelengths of 210-380 nm and of which the inside is visible; and a photostabilization method therefor.

Description

Photostabilized Formulation of Atropine-Containing Aqueous Pharmaceutical Composition and Method for Its Photostabilization 【0001】 The present invention relates to a photostabilized formulation of an aqueous pharmaceutical composition containing atropine or a salt thereof (hereinafter also simply referred to as "atropine") (hereinafter also simply referred to as "the formulation of the present invention") and a method for its photostabilization (hereinafter also simply referred to as "the method of the present invention"). 【0002】 Atropine is a drug known to have the property of suppressing the elongation of the axial length of the eye. For example, Patent Document 1 discloses that a composition containing less than 0.025% of atropine suppresses or prevents the progression of myopia. Further, Patent Document 2 discloses an atropine-containing aqueous composition having an action of suppressing the elongation of the axial length of the eye and an action of improving refractive disorders. 【0003】 In order to develop a compound useful as an active ingredient of a pharmaceutical as a pharmaceutical product, it is required to satisfy various requirements such as the effectiveness and safety of the pharmaceutical product, of course, as well as the stability of the compound in the pharmaceutical composition and the stability of the pharmaceutical composition as a whole. Among these, ensuring the stability of the compound in the pharmaceutical composition is extremely important for the stable exertion of the effect of the pharmaceutical. 【0004】 So far, it has not been known that an aqueous pharmaceutical composition containing atropine at a low concentration of less than 1% is unstable to light of a specific wavelength, and there is no description or suggestion in any literature. 【0005】 WO2012 / 161655 WO2017 / 204262 【0006】The present inventors have found that when an aqueous pharmaceutical composition containing atropine at a low concentration of less than 1% is exposed to light of a specific wavelength, the atropine content decreases. Until now, it has not been known that aqueous pharmaceutical compositions containing atropine at a low concentration of less than 1% are unstable when exposed to light of a specific wavelength. Preventing such a decrease in atropine content would improve the quality of the formulation and is therefore of great significance in the development of pharmaceutical formulations. Accordingly, the object of the present invention is to provide an atropine-containing ophthalmic pharmaceutical formulation that exhibits excellent stability even when exposed to light of a specific wavelength (for example, 210 to 380 nm), by preventing a decrease in the atropine content in an aqueous pharmaceutical composition containing atropine at a low concentration of less than 1% when exposed to light of a specific wavelength (for example, 210 to 380 nm), and to provide the same as a method for photostabilizing the formulation. 【0007】 The present inventors, having newly identified the above-mentioned problems and diligently studied to solve them, discovered that by encapsulating an atropine-containing aqueous pharmaceutical composition with a low concentration of less than 1% in a packaging that blocks light of a specific wavelength, it is possible to provide an atropine-containing ophthalmic pharmaceutical preparation that exhibits excellent stability even against light of a specific wavelength, and a method for photostabilizing the same, thus completing the present invention. 【0008】Specifically, the present invention provides the following: (Item A-1) An ophthalmic pharmaceutical preparation comprising an aqueous pharmaceutical composition containing atropine or a salt thereof at a concentration of 0.001 to 0.1% (w / v), contained in a primary packaging that is visible inside and blocks light rays with wavelengths of 210 to 380 nm. (Item A-2) The ophthalmic pharmaceutical preparation according to Item A-1, wherein the primary packaging blocks light rays with wavelengths of 216 to 372 nm. (Item A-3) The ophthalmic pharmaceutical preparation according to Item A-1, wherein the primary packaging blocks light rays with wavelengths of 279 to 372 nm. (Item A-4) The ophthalmic pharmaceutical preparation according to any one of Items A-1 to A-3, wherein the primary packaging has a light transmittance or average value of 80% or less for light rays with wavelengths of 279 to 372 nm. (Item A-5) The ophthalmic pharmaceutical preparation according to any one of Items A-1 to A-4, wherein the primary packaging is a plastic container. (Item A-6) The ophthalmic pharmaceutical preparation according to Item A-5, wherein the plastic container is a polyethylene resin container, a polypropylene resin container, a polyethylene terephthalate resin container, or a cycloolefin resin container. (Item A-7) The ophthalmic pharmaceutical preparation according to any one of Items A-1 to A-6, wherein the primary packaging is contained within the secondary packaging. (Item A-8) The ophthalmic pharmaceutical preparation according to Item A-7, wherein the secondary packaging is a label, medicine bag, paper box, or pillow packaging. (Item A-9) The ophthalmic pharmaceutical preparation comprising an aqueous pharmaceutical composition containing atropine or a salt thereof at a concentration of 0.001 to 0.1% (w / v), contained in a plastic container with a visible interior, wherein the plastic container is contained in packaging that blocks light rays with wavelengths of 210 to 380 nm, and the packaging is a label, medicine bag, paper box, or pillow packaging. (Item A-10) An ophthalmic pharmaceutical preparation according to Item A-9, wherein the packaging is a label, medicine bag, paper box, or pillow packaging that blocks light rays with wavelengths of 279 to 372 nm. (Item A-11) An ophthalmic pharmaceutical preparation according to Item A-9 or 10, wherein the packaging is a label, medicine bag, paper box, or pillow packaging with a light transmittance or average value of 20% or less for light rays with wavelengths of 279 to 372 nm. (Item A-12) An ophthalmic pharmaceutical preparation according to any one of Items A-1 to 11, wherein the aqueous pharmaceutical composition is an aqueous eye drop solution.(Item A-13) An ophthalmic pharmaceutical preparation according to any one of items A-1 to A-12, wherein the concentration of atropine or a salt thereof is 0.01 to 0.025% (w / v). (Item A-14) An ophthalmic pharmaceutical preparation according to any one of items A-1 to A-13, wherein the atropine or salt thereof is atropine sulfate or a hydrate thereof. (Item A-15) A method for photostabilizing atropine or a salt in an aqueous pharmaceutical composition, comprising the step of housing the aqueous pharmaceutical composition containing atropine or a salt thereof at a concentration of 0.001 to 0.1% (w / v) in a primary packaging that allows the interior to be seen and blocks light rays with a wavelength of 210 to 380 nm. (Item A-16) The method according to item A-15, wherein the primary packaging blocks light rays with a wavelength of 216 to 372 nm. (A-17) The method according to A-15 or 16, wherein the primary packaging blocks light rays with wavelengths of 279 to 372 nm. (A-18) The method according to any one of A-15 to 17, wherein the primary packaging has a light transmittance or average value of 80% or less for light rays with wavelengths of 279 to 372 nm. (A-19) The method according to any one of A-15 to 18, wherein the primary packaging is a plastic container. (A-20) The method according to A-19, wherein the plastic container is a polyethylene resin container, a polypropylene resin container, a polyethylene terephthalate resin container, or a cycloolefin resin container. (A-21) The method according to any one of A-15 to 20, further comprising the step of housing the primary packaging inside a secondary packaging. (A-22) The method according to A-21, wherein the secondary packaging is a label, a medicine bag, a cardboard box, or pillow packaging. (Item A-23) A method for photostabilizing atropine or a salt in an aqueous pharmaceutical composition, comprising the steps of: housing an aqueous pharmaceutical composition containing atropine or a salt thereof at a concentration of 0.001 to 0.1% (w / v) in a plastic container in which the interior is visible; and housing the plastic container in a packaging body that blocks light rays with wavelengths of 210 to 380 nm, wherein the packaging body is a label, medicine bag, paper box, or pillow packaging. (Item A-24) The method according to Item A-23, wherein the packaging body is a label, medicine bag, paper box, or pillow packaging that blocks light rays with wavelengths of 279 to 372 nm.(Item A-25) The method according to item A-23 or 24, wherein the packaging is a label, medicine bag, paper box, or pillow packaging with a light transmittance or average value of 20% or less for light with wavelengths of 279 to 372 nm. (Item A-26) The method according to any one of items A-15 to 25, wherein the aqueous pharmaceutical composition is an aqueous eye drop solution. (Item A-27) The method according to any one of items A-15 to 26, wherein the concentration of atropine or a salt thereof is 0.01 to 0.025% (w / v). (Item A-28) The method according to any one of items A-15 to 27, wherein atropine or a salt thereof is atropine sulfate or a hydrate thereof. 【0009】 Furthermore, two or more of the configurations described in items A-1 to A-28 above can be arbitrarily selected and combined. 【0010】The present invention also provides the following: (Item B-1) An ophthalmic pharmaceutical preparation comprising an aqueous pharmaceutical composition containing atropine or a salt thereof at a concentration of 0.001 to 0.1% (w / v), contained in a primary packaging that blocks light rays with wavelengths of 210 to 380 nm. (Item B-2) The ophthalmic pharmaceutical preparation according to Item B-1, wherein the interior of the primary packaging is visible. (Item B-3) The ophthalmic pharmaceutical preparation according to Item B-1 or 2, wherein the primary packaging blocks light rays with wavelengths of 216 to 372 nm. (Item B-4) The ophthalmic pharmaceutical preparation according to Item B-1 or 2, wherein the primary packaging blocks light rays with wavelengths of 247 to 372 nm. (Item B-5) The ophthalmic pharmaceutical preparation according to Item B-1 or 2, wherein the primary packaging blocks light rays with wavelengths of 279 to 372 nm. (Item B-6) An ophthalmic pharmaceutical preparation according to any one of items B-1 to B-5, wherein the primary packaging has a light transmittance or average value of 279 to 372 nm wavelengths of 80% or less. (Item B-7) An ophthalmic pharmaceutical preparation according to any one of items B-1 to B-5, wherein the primary packaging has a light transmittance or average value of 279 to 372 nm wavelengths of 70% or less. (Item B-8) An ophthalmic pharmaceutical preparation according to any one of items B-1 to B-7, wherein the primary packaging is a plastic container. (Item B-9) An ophthalmic pharmaceutical preparation according to item B-8, wherein the plastic container is a polyethylene resin container, a polypropylene resin container, a polyethylene terephthalate resin container, or a cycloolefin resin container. (Item B-10) An ophthalmic pharmaceutical preparation according to any one of items B-1 to B-9, wherein the primary packaging is contained within a secondary packaging. (Item B-11) The ophthalmic pharmaceutical preparation according to Item B-10, wherein the secondary packaging is a label, medicine bag, cardboard box, or pillow packaging. (Item B-12) The ophthalmic pharmaceutical preparation according to Item B-11, wherein the label is a paper label or shrink label. (Item B-13) The ophthalmic pharmaceutical preparation comprising an aqueous pharmaceutical composition containing atropine or a salt thereof at a concentration of 0.001 to 0.1% (w / v), contained in a plastic container with a visible interior, and the plastic container contained in packaging that blocks light rays with wavelengths of 210 to 380 nm, wherein the packaging is a label, medicine bag, cardboard box, or pillow packaging.(Item B-14) An ophthalmic pharmaceutical preparation according to Item B-13, wherein the packaging is a label, medicine bag, paper box, or pillow packaging that blocks light rays with wavelengths of 279 to 372 nm. (Item B-15) An ophthalmic pharmaceutical preparation according to Item B-13 or 14, wherein the packaging is a label, medicine bag, paper box, or pillow packaging whose light transmittance or average value of light rays with wavelengths of 279 to 372 nm is 20% or less. (Item B-16) An ophthalmic pharmaceutical preparation according to any one of Items B-13 to 15, wherein the packaging is a medicine bag, and the medicine bag is a medicine bag containing an ultraviolet absorber. (Item B-17) An ophthalmic pharmaceutical preparation according to any one of Items B-1 to 16, wherein the aqueous pharmaceutical composition is an aqueous eye drop solution. (Item B-18) An ophthalmic pharmaceutical preparation according to any one of items B-1 to B-17, wherein the concentration of atropine or a salt thereof is 0.001 to 0.025% (w / v). (Item B-19) An ophthalmic pharmaceutical preparation according to any one of items B-1 to B-17, wherein the concentration of atropine or a salt thereof is 0.01 to 0.025% (w / v). (Item B-20) An ophthalmic pharmaceutical preparation according to any one of items B-1 to B-19, wherein the atropine or a salt thereof is atropine sulfate or a hydrate thereof. (Item B-21) A method for photostabilizing atropine or a salt in an aqueous pharmaceutical composition, comprising the step of housing the aqueous pharmaceutical composition containing atropine or a salt thereof at a concentration of 0.001 to 0.1% (w / v) in a primary packaging that blocks light rays with a wavelength of 210 to 380 nm. (Item B-22) The method according to item B-21, wherein the interior of the primary packaging is visible. (Item B-23) The method according to item B-21 or 22, wherein the primary packaging blocks light rays with wavelengths of 216 to 372 nm. (Item B-24) The method according to item B-21 or 22, wherein the primary packaging blocks light rays with wavelengths of 247 to 372 nm. (Item B-25) The method according to item B-21 or 22, wherein the primary packaging blocks light rays with wavelengths of 279 to 372 nm. (Item B-26) The method according to any one of items B-21 to 25, wherein the primary packaging has a light transmittance or average value of 80% or less for light rays with wavelengths of 279 to 372 nm. (Item B-27) The method according to any one of items B-21 to B-25, wherein the primary packaging has a light transmittance or average value of 70% or less for light with wavelengths of 279 to 372 nm.(Section B-28) The method according to any one of sections B-21 to B-27, wherein the primary packaging is a plastic container. (Section B-29) The method according to section B-28, wherein the plastic container is a polyethylene resin container, a polypropylene resin container, a polyethylene terephthalate resin container, or a cycloolefin resin container. (Section B-30) The method according to any one of sections B-21 to B-29, further comprising the step of housing the primary packaging inside a secondary packaging. (Section B-31) The method according to section B-30, wherein the secondary packaging is a label, a medicine bag, a cardboard box, or pillow packaging. (Section B-32) The method according to section B-31, wherein the label is a paper label or a shrink label. (Item B-33) A method for photostabilizing atropine or a salt in an aqueous pharmaceutical composition, comprising the steps of: housing an aqueous pharmaceutical composition containing atropine or a salt thereof at a concentration of 0.001 to 0.1% (w / v) in a plastic container whose interior is visible; and housing the plastic container in a packaging body that blocks light rays with wavelengths of 210 to 380 nm, wherein the packaging body is a label, medicine bag, paper box, or pillow packaging. (Item B-34) The method according to item B-33, wherein the packaging body is a label, medicine bag, paper box, or pillow packaging that blocks light rays with wavelengths of 279 to 372 nm. (Item B-35) The method according to item B-33 or 34, wherein the packaging body is a label, medicine bag, paper box, or pillow packaging with a light transmittance or average value of 20% or less for light rays with wavelengths of 279 to 372 nm. (Item B-36) The method according to any one of items B-33 to 35, wherein the packaging is a medicine bag, and the medicine bag is a medicine bag containing an ultraviolet absorber. (Item B-37) The method according to any one of items B-21 to 36, wherein the aqueous pharmaceutical composition is an aqueous eye drop solution. (Item B-38) The method according to any one of items B-21 to 37, wherein the concentration of atropine or a salt thereof is 0.001 to 0.025% (w / v). (Item B-39) The method according to any one of items B-21 to 37, wherein the concentration of atropine or a salt thereof is 0.01 to 0.025% (w / v). (Item B-40) The method according to any one of items B-21 to 39, wherein the atropine or a salt thereof is atropine sulfate or a hydrate thereof. 【0011】Furthermore, two or more of the components described in items B-1 to B-40 above can be arbitrarily selected and combined. 【0012】 According to the present invention, by encapsulating an aqueous pharmaceutical composition containing atropine at a low concentration of less than 1% in a packaging that blocks light of a specific wavelength, an atropine-containing ophthalmic pharmaceutical formulation exhibiting excellent stability even with respect to light of a specific wavelength can be obtained. Furthermore, the formulation of the present invention has sufficient photostability as a pharmaceutical product. Moreover, the method of the present invention is a useful method for providing the formulation of the present invention. 【0013】 The results of measuring the light transmittance (%) of light rays at each wavelength for various packaging materials (Examples 1 to 6) are shown. The results of measuring the light transmittance (%) of light rays at each wavelength for various packaging materials (Examples 7 to 10) are shown. 【0014】 The present invention will be described in detail below. 【0015】 The aqueous pharmaceutical composition of the present invention contains "atropine or a salt thereof" as an active ingredient. "Atropine or a salt thereof" also includes (i) a hydrate of atropine or a salt thereof, (ii) an organic solvent hydrate of atropine or a salt thereof, and (iii) a mixture of the hydrate and the organic solvent hydrate. The atropine salt includes atropine sulfate or its hydrate, preferably atropine sulfate hydrate. 【0016】 Atropine sulfate hydrate is a compound represented by the following structural formula. 【0017】 If atropine or its salts have crystalline polymorphs and groups of crystalline polymorphs (polymorphic systems), then these crystalline polymorphs and groups of crystalline polymorphs (polymorphic systems) are also included within the scope of the present invention. Here, a group of crystalline polymorphs (polymorphic systems) means not only the individual crystalline forms obtained at each stage when the crystalline form changes depending on the conditions and state of the production, crystallization, storage, etc. of those crystals, but also mixtures of crystalline forms obtained at two or more stages. 【0018】Atropine or its salts can be prepared according to common methods in the field of organic synthesis chemistry, or commercially available products can be used. For example, atropine sulfate hydrate is commercially available from Tokyo Chemical Industry Co., Ltd. (product code: A0550). 【0019】 In the present invention, "% (w / v)" means the mass (g) of the target component contained in 100 mL of the aqueous pharmaceutical composition of the present invention. For example, if a salt of atropine is contained in the present invention, the value is the content of the salt of atropine. Also, if atropine or a salt of 【0020】 In the present invention, the concentration of atropine or its salt is preferably 0.001 to 0.1% (w / v), more preferably 0.001 to 0.05% (w / v), even more preferably 0.001 to 0.025% (w / v), and particularly preferably 0.01 to 0.025% (w / v). More specifically, the concentrations are 0.0010% (w / v), 0.0015% (w / v), 0.0020% (w / v), 0.0025% (w / v), 0.0030% (w / v), 0.0035% (w / v), 0.0040% (w / v), 0.0045% (w / v), 0.0050% (w / v), 0.0055% (w / v), 0.0060% (w / v), 0.0065% (w / v), 0.0070% (w / v), 0.0075% ( w / v), 0.0080% (w / v), 0.0085% (w / v), 0.0090% (w / v), 0.0095% (w / v), 0.010% ( w / v), 0.011% (w / v), 0.012% (w / v), 0.013% (w / v), 0.014% (w / v), 0.015% (w / v), 0.016% (w / v), 0.017% (w / v), 0.018% (w / v), 0.019% (w / v), 0.020% (w / v), 0.02 1% (w / v), 0.022% (w / v), 0.023% (w / v), 0.024% (w / v), or 0.025% (w / v). 【0021】In the present invention, "aqueous pharmaceutical composition" means a pharmaceutical composition containing water as a solvent. 【0022】 In the present invention, additives may be used in the aqueous pharmaceutical composition as needed. These additives may include water-soluble polymers, buffers, isotonic agents, surfactants, stabilizers, preservatives, antioxidants, high molecular weight polymers, pH adjusters, and bases. These may be used individually or in combination of two or more as appropriate, and appropriate amounts may be added. 【0023】 Examples of formulations of the aqueous pharmaceutical composition of the present invention include eye drops or aqueous eye solutions. 【0024】The aqueous pharmaceutical composition of the present invention may appropriately contain water-soluble polymers that can be used as additives to pharmaceuticals. In the present invention, "water-soluble polymer" means any pharmaceutically acceptable polymer that is soluble in water. Examples of water-soluble polymers include celluloses and their derivatives (e.g., methylcellulose, hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, carboxymethyl ethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, cellulose acetate phthalate, ethylcellulose, hydroxymethylcellulose, hydroxyethyl methylcellulose, hypromellose acetate succinate, and hypromellose phthalate), synthetic polymers (e.g., polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, and carboxyvinyl polymer), and polymers and saccharides derived from natural products (e.g., gum arabic, sodium alginate, propylene glycol alginate, agar, gelatin, tragacanth, and xanthan gum). Preferred water-soluble polymers include cellulose and its derivatives, carboxyvinyl polymers, and sodium alginate. More preferred polymers include hydroxyethylcellulose, carboxyvinyl polymers, and hydroxypropylmethylcellulose. These water-soluble polymers may be used individually or in any combination of two or more components. 【0025】 When the aqueous pharmaceutical composition of the present invention contains a water-soluble polymer, the concentration of the water-soluble polymer can be appropriately adjusted depending on the type of water-soluble polymer, but 0.01 to 5% (w / v) is preferred, and 0.1 to 2% (w / v) is more preferred. 【0026】For example, when the water-soluble polymer is cellulose and its derivatives, the concentration of cellulose and its derivatives is preferably 0.01 to 5% (w / v), more preferably 0.1 to 2% (w / v), even more preferably 0.1 to 1% (w / v), and particularly preferably 0.1 to 0.6% (w / v). For example, when the water-soluble polymer is hydroxyethylcellulose, the concentration of hydroxyethylcellulose is preferably 0.1 to 1.0% (w / v), more preferably 0.1 to 0.6% (w / v). For example, when the water-soluble polymer is carboxyvinyl polymer, the concentration of carboxyvinyl polymer is preferably 0.04 to 0.4% (w / v), more preferably 0.08 to 0.4% (w / v). For example, when the water-soluble polymer is hydroxypropylmethylcellulose, the concentration of hydroxypropylmethylcellulose is preferably 0.1 to 1.0% (w / v), more preferably 0.1 to 0.6% (w / v). For example, when the water-soluble polymer is sodium alginate, the concentration of sodium alginate is preferably 0.1 to 2% (w / v), and more preferably 0.5 to 2% (w / v). 【0027】The aqueous pharmaceutical composition of the present invention may appropriately contain buffering agents that can be used as additives to pharmaceuticals. In the present invention, the "buffering agent" is not particularly limited as long as it is pharmaceutically acceptable, and examples include phosphate buffering agents, citrate buffering agents, borate buffering agents, carbonate buffering agents, acetate buffering agents, tartaric acid buffering agents, aminocarboxylic acid buffering agents, trometamol, etc. Examples of aminocarboxylic acid buffering agents include aspartate buffering agents, glutamate buffering agents, epsilon-aminocaproic acid, etc. Preferably, buffering agents include phosphate buffering agents, citrate buffering agents, carbonate buffering agents, acetate buffering agents, and aminocarboxylic acid buffering agents, more preferably phosphate buffering agents, citrate buffering agents, acetate buffering agents, and aminocarboxylic acid buffering agents, even more preferably phosphate buffering agents and / or citrate buffering agents, and particularly preferably phosphate buffering agents and citrate buffering agents. These buffering agents may be used individually or in any combination of two or more components. 【0028】 When the aqueous pharmaceutical composition of the present invention contains a buffer, the concentration of the buffer can be appropriately adjusted depending on the type of buffer, etc., but is preferably 0.001 to 10% (w / v), more preferably 0.01 to 5% (w / v), even more preferably 0.01 to 3% (w / v), even more preferably 0.01 to 1% (w / v), particularly preferably 0.01 to 0.5% (w / v), and most preferably 0.01 to 0.1% (w / v). 【0029】 Examples of phosphate buffering agents include phosphates such as phosphoric acid, alkali metal phosphates, and alkaline earth metal phosphates, as well as their hydrates. More specifically, examples include sodium hydrogen phosphate hydrate (also called "sodium hydrogen phosphate" or "sodium phosphate"), sodium dihydrogen phosphate (also called "monosodium phosphate"), sodium dihydrogen phosphate monohydrate (also called "monosodium phosphate"), sodium dihydrogen phosphate dihydrate (also called "monosodium phosphate"), potassium dihydrogen phosphate (also called "monosodium phosphate"), sodium hydrogen phosphate heptahydrate, trisodium phosphate, and dipotassium phosphate. 【0030】Examples of citrate buffers include citrates such as citric acid, alkali metal citrate, and alkaline earth metal citrate, as well as their hydrates. More specifically, examples include citric acid hydrate, sodium citrate, sodium citrate hydrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, and disodium citrate. 【0031】 Examples of boric acid buffers include boric acid or its salts, borax, etc. More specifically, examples include boric acid, sodium borate, potassium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc. 【0032】 Examples of carbonate buffers include carbonic acid or its salts. More specifically, examples include carbonic acid, sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc. 【0033】 Examples of acetic acid buffers include acetic acid or its salts. More specifically, examples include acetic acid, ammonium acetate, potassium acetate, calcium acetate, and sodium acetate. 【0034】 Examples of tartaric acid buffers include tartaric acid or its salts. More specifically, sodium tartrate and potassium tartrate are examples. 【0035】 Examples of aspartic acid buffers include aspartic acid or its salts. More specifically, sodium aspartate and magnesium aspartate are examples. 【0036】 Examples of glutamate buffers include glutamic acid or its salts. More specifically, examples include monosodium glutamate and potassium glutamate. 【0037】The aqueous pharmaceutical composition of the present invention may optionally contain an isotonic agent that can be used as an additive to pharmaceuticals. In the present invention, the "isotonic agent" is not particularly limited as long as it is pharmaceutically acceptable, and examples include nonionic isotonic agents such as glycerin, mannitol, propylene glycol, polyethylene glycol, glucose, sorbitol, xylitol, and trehalose. Preferred nonionic isotonic agents include glycerin, mannitol, propylene glycol, polyethylene glycol, glucose, sorbitol, xylitol, and trehalose, more preferably glycerin and mannitol, and particularly preferably glycerin. These isotonic agents may be used individually or in any combination of two or more components. 【0038】 When the aqueous pharmaceutical composition of the present invention contains an isotonic agent, the content of the isotonic agent can be appropriately adjusted depending on the type of isotonic agent, but 0.01 to 10% (w / v) is preferred, 0.05 to 5% (w / v) is more preferred, 0.1 to 5% (w / v) is even more preferred, 0.5 to 5% (w / v) is even more preferred, and 1 to 5% (w / v) is particularly preferred. 【0039】 The pH of the aqueous pharmaceutical composition of the present invention is not limited to a specific value as long as it is within a pharmaceutically acceptable range. Preferably, the pH is in the range of 6 or less, more preferably 4 to 6, even more preferably 4 to 5, and particularly preferably in the vicinity of 4 or 5. More specifically, examples include pH 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, etc. 【0040】The osmotic pressure of the aqueous pharmaceutical composition of the present invention is not limited to a specific value, but is within a range acceptable to living organisms. Examples of osmotic pressures of the aqueous pharmaceutical composition of the present invention include 100 to 1000 mOsm. Preferably, the osmotic pressure of the aqueous pharmaceutical composition of the present invention is 200 to 500 mOsm, and more preferably 250 to 350 mOsm. Generally, the osmotic pressure of an aqueous pharmaceutical composition is affected to some extent by the amount of drugs and additives in the aqueous pharmaceutical composition. In the present invention, the osmotic pressure can be adjusted to fall within the above range by appropriately adjusting the amounts of these substances that can affect the osmotic pressure. It should be noted that the osmotic pressure of the aqueous pharmaceutical composition of the present invention can be measured by conventional methods. For example, the osmotic pressure of the aqueous pharmaceutical composition of the present invention can be measured according to the method described in the "Osmotic Pressure Measurement Method (Osmolar Concentration Measurement Method)" of the 18th edition of the Japanese Pharmacopoeia. 【0041】 The viscosity of the aqueous pharmaceutical composition of the present invention is not limited to a specific value, but for example, it is 5 to 70 mPa·s. Preferably, the viscosity of the aqueous pharmaceutical composition of the present invention is 5 to 60 mPa·s, more preferably 8 to 50 mPa·s, even more preferably 10 to 45 mPa·s, particularly preferably 10 to 40 mPa·s, and most preferably 15 to 35 mPa·s. Generally, the viscosity of an aqueous pharmaceutical composition is affected to some extent by the amount of drugs and additives in the aqueous pharmaceutical composition. In the present invention, the viscosity can be adjusted to fall within the above range by appropriately adjusting the amounts of these substances that can affect the viscosity. It should be noted that the viscosity of the aqueous pharmaceutical composition of the present invention can be measured by conventional methods. For example, the viscosity of the aqueous pharmaceutical composition of the present invention can be measured according to the method described in the second method, "rotational viscometer method," of the "viscosity measurement method" of the 18th edition of the Japanese Pharmacopoeia. 【0042】 In the present invention, the aqueous pharmaceutical composition can be administered orally or parenterally. Administration routes include oral administration, intravenous administration, transdermal administration, and local ocular administration (e.g., eye drops, conjunctival sac administration, intravitreous administration, subconjunctival administration, sub-Tenon's capsule administration). 【0043】The ophthalmic pharmaceutical preparation of the present invention is not particularly limited as long as it can be contained in a package described later, and can be used in dosage forms for ophthalmic diseases, such as eye drops, eye gels, injections, etc. The ophthalmic pharmaceutical preparation of the present invention is particularly preferably used as eye drops. These dosage forms can be produced according to ordinary methods in the art. 【0044】 The ophthalmic pharmaceutical preparation of the present invention is provided by containing an aqueous pharmaceutical composition in a package that blocks light rays in a specific wavelength range. The package only needs to be able to block light rays in a specific wavelength range in the storage state normally assumed for the pharmaceutical preparation, and its hermeticity is not particularly limited. Also, the means for containing the aqueous pharmaceutical composition in the package may be filled by a conventional method according to the form of the package, etc. 【0045】 In the present invention, "package" means something that directly or indirectly contains the aqueous pharmaceutical composition of the present invention. "Primary package" means something that directly contains the aqueous pharmaceutical composition of the present invention. "Secondary package" means something that indirectly contains the aqueous pharmaceutical composition of the present invention. 【0046】 Examples of the primary package include eye drop containers, injection containers, tube-shaped containers, bottle-shaped containers, spray containers, etc. The primary package is preferably one with a visible interior. Examples of the secondary package include labels (paper labels, shrink labels, etc.), medicine bags, cardboard boxes, pillow packaging (pouches, aluminum pillows, etc.), cases, etc. The medicine bags include those that are light-shielding and transparent. 【0047】 In the present invention, "containing the primary package in the secondary package" includes, in addition to containing the primary package in the secondary package, attaching a label or the like around the primary package. Specific examples of "containing the primary package in the secondary package" include containing a plastic container or the like, which is the primary package, in a secondary package such as a medicine bag. Also, attaching a label (paper label, shrink label, etc.), which is the secondary package, around a plastic container or the like, which is the primary package, is also included. 【0048】In the present invention, the wavelength range of light rays blocked by the packaging is 210 to 380 nm, preferably 216 to 372 nm, more preferably 247 to 372 nm, particularly preferably 279 to 372 nm, and most preferably 279, 310, 341, or 372 nm. Another embodiment of the wavelength range of light rays blocked by the packaging is 216, 247, 279, 310, 341, or 372 nm. 【0049】 In the present invention, "blocking light rays" in the wavelength range means that the light transmittance of light rays in that wavelength range is 90% or less, or the light shielding rate is greater than 10%, or the average value of the light transmittance of light rays in that wavelength range is 90% or less, or the average value of the light shielding rate is greater than 10%. For example, "blocking light rays with wavelengths of 210 to 380 nm" means that the light transmittance of light rays with wavelengths of 210 to 380 nm or the average value of the light transmittance of light rays with wavelengths of 210 to 380 nm is 90% or less. In the present invention, the light transmittance or average value of light rays with wavelengths of 210 to 380 nm is preferably 80% or less, more preferably 70% or less, even more preferably 50% or less, particularly preferably 30% or less, and most preferably 10% or less, from the viewpoint of further improving stability against light. Examples of light transmittance or average light transmittance for light rays in the wavelength range include 90% or less, 85% or less, 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, and 10% or less. 【0050】In the present invention, the method for measuring light transmittance can be calculated by measuring the light transmittance at wavelengths of 210 to 800 nm using an ultraviolet-visible spectrometer. It is not necessary for the entire package to block light rays in the aforementioned wavelength range, but it is preferable that 50% or more of the total area of ​​the inner surface of the package blocks light rays in the aforementioned wavelength range, more preferably 60% or more, even more preferably 70% or more, even more preferably 80% or more, particularly preferably 90% or more, particularly more preferably 95% or more, and most preferably 100%. As an example of a configuration in which a portion of the total surface area of ​​the inner surface of the packaging blocks light rays in the wavelength range, this includes a configuration in which a label (shrink label, paper label, etc.) that blocks light rays in the wavelength range is wrapped around the side of a primary packaging (such as an eye drop container) that does not block light rays in the wavelength range. 【0051】 If the ophthalmic pharmaceutical formulation of the present invention includes a secondary packaging, it is sufficient that either the primary packaging or the secondary packaging blocks light rays in the aforementioned wavelength range. Furthermore, even if the primary packaging and the secondary packaging cannot block light rays in the aforementioned wavelength range individually, it is sufficient that the combination of the primary and secondary packaging blocks light rays in the aforementioned wavelength range. Multiple secondary packaging may be used. From the viewpoint of suppressing the degradation of atropine or its salt not only during distribution and storage but also during use, it is preferable that the primary packaging of the ophthalmic pharmaceutical formulation of the present invention blocks light rays in a specific wavelength range. 【0052】 In the present invention, the material of the packaging body is not particularly limited, but examples include plastic, cellulose, pulp, rubber, metal, and the like. 【0053】As the primary packaging, a plastic container is preferred. Examples of plastic containers include polyethylene resin containers, polypropylene resin containers, polyethylene terephthalate resin containers, cycloolefin resin containers, etc. Furthermore, from the viewpoint of visibility of the contents, a transparent container is preferred as the primary packaging. In the case of a transparent container, it is sufficient that it is transparent enough that the contents can be seen. Sufficiently transparent means that the light transmittance or average value of visible light (wavelength approximately 400 nm to approximately 800 nm) is, for example, 5% or more, preferably 8% or more, more preferably 25% or more, even more preferably 35% or more, even more preferably 45% or more, particularly preferably 55% or more, particularly more preferably 65% ​​or more, and most preferably 75% or more. It is not necessary for the entire surface of the container to be transparent enough to allow visibility of the interior, but it is preferable that 30% or more of the total surface area of ​​the outer surface of the container be transparent, more preferably 50% or more, even more preferably 70% or more, even more preferably 80% or more, particularly preferably 90% or more, and most preferably 95% or more. One aspect of the primary packaging being visible is that the transmittance of light with a wavelength of 400 nm or more is 8% or more. 【0054】From the viewpoint of processability and other factors, the material of the secondary packaging is preferably made of plastic, cellulose, pulp, paper, etc. The secondary packaging does not have to be transparent, but it may be transparent from the viewpoint of visibility of the contents. If the secondary packaging is transparent, it is sufficient that the contents are visible. Sufficiently transparent means that the light transmittance or average value of visible light (wavelength approximately 400 nm to approximately 800 nm) is, for example, 5% or more, preferably 15% or more, more preferably 25% or more, even more preferably 35% or more, even more preferably 45% or more, particularly preferably 55% or more, particularly more preferably 65% ​​or more, and most preferably 75% or more. While it is not necessary for the entire secondary packaging to be transparent enough to allow visibility of the contents, it is preferable that 1% or more of the total surface area of ​​the secondary packaging's outer surface be transparent, more preferably 5% or more, more preferably 10% or more, even more preferably 30% or more, even more preferably 50% or more, particularly preferably 90% or more, and most preferably 95% or more. Furthermore, one embodiment of the secondary packaging includes a transparent slit (visibility window) for viewing the contents. 【0055】In the present invention, "polyethylene (PE) resin container" (hereinafter also referred to as "PE container") means a container in which at least the portion of the container that comes into contact with the aqueous pharmaceutical composition is made of polyethylene resin. Examples of polyethylene include low-density polyethylene (LDPE), medium-density polyethylene (MDPE), and high-density polyethylene (HDPE). Furthermore, "polypropylene (PP) resin container" (hereinafter also referred to as "PP container") means a container in which at least the portion of the container that comes into contact with the aqueous pharmaceutical composition is made of polypropylene resin. "Polyethylene terephthalate (PET) resin container" (hereinafter also referred to as "PET container") means a container in which at least the portion of the container that comes into contact with the aqueous pharmaceutical composition is made of polyethylene terephthalate resin. "Cycloolefin resin container" (hereinafter also referred to as "COP container") means a container in which at least the portion of the container that comes into contact with the aqueous pharmaceutical composition is made of cycloolefin resin. 【0056】 Means for blocking light rays from the packaging include, for example, a method of incorporating light-shielding materials such as pigments, dyes, ultraviolet absorbers, or ultraviolet scattering agents into the packaging material; a method of coating the packaging with such light-shielding materials; a method of covering the packaging with a film containing such light-shielding materials; a method of forming the packaging with a sheet made by laminating layers containing such light-shielding materials; a method of covering the packaging with a film coated with such light-shielding materials; a method of forming the packaging with a sheet made by laminating metal foil such as aluminum foil; and a method of forming the packaging with such a metal sheet. 【0057】Examples of UV absorbers include UVA absorbers such as terephthalylidene disulfonic acid, 2-ethylhexyl dimethoxybenzylidene oxoimidazolidine propionate, hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate, and 4-tert-butyl-4'-methoxydibenzoylmethane; 2-ethylhexyl paramethoxycinnamate, isopropyl paramethoxycinnamate, para-aminobenzoic acid (hereinafter also referred to as "PABA"), ethyl PABA, ethyl-dihydroxypropyl PABA, ethylhexyl-dimethyl PABA, homosalate, ethylhexyl salicylate, 3-benzylidene camphor, 4-methylbenzylidene camphor, benzylidene camphor sulfonic acid, and camphor benzalconyl methosulfate. Examples of UVB absorbers include polyacrylamide methylbenzylidene camphor, diethylhexylbutamide triazone, 2,4,6-tris[4-(2-ethylhexyloxycarbonyl)anilino]-1,3,5-triazine, phenyldibenzimidazole tetrasulfonate disodium, polyorganosiloxane having a benzalmalonate functional group, and octocrylene; and UVAB absorbers such as benzophenone-2, benzophenone-3 or oxybenzone, benzophenone-4, 2,4-bis-[{4-(2-ethylhexyloxy)-2-hydroxy}phenyl]-6-(4-methoxyphenyl)-1,3,5-triazine, drometrizole trisiloxane, and methylenebisbenzotriazolyltetramethylbutylphenol. Examples of ultraviolet scattering agents include titanium dioxide. 【0058】When the ophthalmic pharmaceutical preparation of the present invention is used as eye drops, the eye drop container may be composed of one component or of multiple components. In the present invention, the aqueous pharmaceutical composition may be contained in, for example, a one-piece eye drop container composed of one component, a two-piece eye drop container composed of two components, or a three-piece eye drop container composed of three components. For example, a three-piece eye drop container is formed from three components: a container body for containing the aqueous pharmaceutical composition, an inner stopper, and a cap. A one-piece molded container in which blow molding and drug solution filling are performed simultaneously is also included in the above eye drop container according to the number of components. When the container is formed from multiple components, the components may be made of the same material or of different materials. 【0059】 When the ophthalmic pharmaceutical formulation of the present invention is used as eye drops, it may be contained in a multi-dose container, a single-use unit-dose container, or a PFMD (Preservative Free Multi-Dose) container. 【0060】 In the present invention, "multi-dose container" refers to an eye drop container comprising a container body and a cap that can be attached to the container body, wherein the cap can be freely opened and resealed. The multi-dose container typically contains multiple doses of eye drops for use over a certain period of time. 【0061】 In the present invention, "unit dose type container" refers to an eye drop container in which a cap is fused and sealed to the neck of the bottle, and which is intended to be opened by breaking the fused portion between the cap and the bottle-shaped body when in use. The unit dose type container may contain an aqueous pharmaceutical composition for single use, or it may contain an aqueous pharmaceutical composition for several uses, for use in a day. 【0062】In the present invention, a "PFMD (Preservative Free Multi-Dose) container" refers to a container whose physical structure ensures sterility within the container even without containing preservatives. Examples of PFMD containers include containers that exhibit a preservative effect by having a backflow prevention valve in the discharge hole, and containers that exhibit a preservative effect by being a delaminated bottle with a filter. Furthermore, PFMD containers also include eye drop containers in which the inner stopper (nozzle) and cap are integrated into a single component until the first opening, and after opening, the inner stopper (nozzle) and cap separate into two components. 【0063】 The dosage and administration of the aqueous pharmaceutical composition of the present invention are not particularly limited as long as they are sufficient to produce the desired pharmacological effect. Preferably, 1 to 3 drops are administered once to 5 times a day, more preferably 1 to 2 drops are administered twice to 4 times a day, and most preferably 1 drop is administered once a day before bedtime. 【0064】 The aqueous pharmaceutical compositions of the present invention can be used, for example, to inhibit or prevent the progression of myopia, and / or to treat myopia. More preferably, they can be used to inhibit or prevent the progression of myopia in school-aged children. "Inhibiting or preventing the progression of myopia" means slowing down or reducing the progression of myopia. "Preventing myopia" means preventing the onset of myopia or delaying the onset of myopia. 【0065】 The present invention also provides a method for photostabilizing atropine or a salt in an aqueous pharmaceutical composition, comprising the step of housing the aqueous pharmaceutical composition containing atropine or a salt in a primary packaging that blocks light of a specific wavelength. Furthermore, the present invention can also provide a method for photostabilizing atropine or a salt in an aqueous pharmaceutical composition, comprising the steps of housing the aqueous pharmaceutical composition containing atropine or a salt in a plastic container whose interior is visible, and housing the plastic container in a medicine bag that blocks light of a specific wavelength. 【0066】 Examples and test examples are shown below, but these are for the purpose of better understanding the present invention and do not limit the scope of the invention. 【0067】Preparation of the test formulation (1) Preparation of 0.025% atropine aqueous solution A 0.025% atropine aqueous solution was prepared by dissolving atropine sulfate hydrate (12.5 mg) in purified water and adjusting the volume to exactly 50 mL. (2) Preparation of 1% atropine aqueous solution A 1% atropine aqueous solution was prepared by dissolving atropine sulfate hydrate (0.5 g) in purified water and adjusting the volume to exactly 50 mL. (3) Preparation of 0.01% atropine aqueous solution A 0.01% atropine aqueous solution was prepared by dissolving atropine sulfate hydrate (10 mg) in purified water and adjusting the volume to exactly 100 mL. 【0068】 Test Example 1: Photostability Test at Each Wavelength (1) The 0.025% atropine aqueous solution prepared above was irradiated for 24 hours at various wavelengths from 216 to 703 nm using a multi-wavelength irradiation spectrometer. The atropine content in the test formulation at each irradiation wavelength after irradiation was quantified using high-performance liquid chromatography, and the remaining percentage (%) was calculated. The remaining percentage (%) of atropine at each measurement wavelength is shown in Table 1. Note that the remaining percentage (%) is the ratio (%) when the atropine content in the test formulation before irradiation is set to 100%. 【0069】 The above test results showed that the 0.025% atropine aqueous solution was unstable when exposed to light with wavelengths of 216 to 372 nm. The properties of the 0.025% atropine aqueous solution remained unchanged before and after exposure to each irradiation wavelength, and it was colorless and transparent. 【0070】 Test Example 2: Photostability Test at Each Wavelength (2) The 1% atropine aqueous solution prepared above was similarly irradiated for 24 hours at each irradiation wavelength from 216 to 703 nm using a multi-wavelength irradiation spectrometer. The atropine content in the test formulation at each irradiation wavelength after irradiation was quantified using high-performance liquid chromatography, and the remaining percentage (%) was calculated. The remaining percentage (%) of atropine at each measurement wavelength is shown in Table 2. Note that the remaining percentage (%) is the ratio (%) when the atropine content in the test formulation before irradiation is set to 100%. 【0071】Test Example 3: Photostability Test at Each Wavelength (3) The 0.01% atropine aqueous solution prepared above was similarly irradiated for 24 hours at each irradiation wavelength from 216 to 703 nm using a multi-wavelength irradiation spectrometer. The atropine content in the test formulation at each irradiation wavelength after irradiation was quantified using high-performance liquid chromatography, and the remaining percentage (%) was calculated. The remaining percentage (%) of atropine at each measurement wavelength is shown in Table 3. Note that the remaining percentage (%) is the ratio (%) when the atropine content in the test formulation before irradiation is set to 100%. 【0072】 The above test results showed that the 1% atropine aqueous solution was more stable against irradiation with light of each wavelength compared to the 0.025% and 0.01% atropine aqueous solutions. 【0073】 The results from the above test examples 1 to 3 surprisingly showed that the stability when exposed to light with irradiation wavelengths of 216 to 372 nm differed depending on the concentration of atropine. 【0074】 Test Example 4: Confirmation of the photostabilization effect of various packaging materials (1) In this test, the photostabilization effect of various packaging materials was evaluated at irradiation wavelengths of ultraviolet A: UV-A (315-400 nm) and ultraviolet B: UV-B (280-315 nm), which are known as ultraviolet rays that can reach the Earth's surface and are particularly important when developing atropine-containing aqueous pharmaceutical compositions as pharmaceuticals. Specifically, the packaging materials of Examples 1 to 6 were cut to fit the slit width (5 mm) and fixed. The 0.025% atropine aqueous solution prepared above was irradiated with 280-380 nm (279 nm, 310 nm, 341 nm, 372 nm) for 24 hours using a multi-wavelength irradiation spectrometer. The atropine content in the test formulation at each irradiation wavelength after irradiation was quantified using high-performance liquid chromatography, and the remaining percentage (%) was calculated. The remaining percentage (%) of atropine in the packaging materials of Examples 1 to 6 is shown in Table 4. The residual rate (%) is the percentage of the atropine content in the test preparation before irradiation, with that content set to 100%. 【0075】The above test results demonstrate that using the various packaging materials of Examples 1 to 6 significantly improved the photostability of the 0.025% atropine aqueous solution when exposed to light of various irradiation wavelengths. 【0076】 Test Example 5: Confirmation of the photostabilization effect of various packaging materials (2) In this test, the photostabilization effect of various packaging materials was evaluated at irradiation wavelengths of ultraviolet A: UV-A (315-400 nm) and ultraviolet B: UV-B (280-315 nm), which are known as ultraviolet rays that can reach the Earth's surface and are particularly important when developing atropine-containing aqueous pharmaceutical compositions as pharmaceuticals. Specifically, the packaging materials of Examples 1 and 5 were cut to fit the slit width (5 mm) and fixed. The 0.01% atropine aqueous solution prepared above was then irradiated with 280-380 nm (279 nm, 310 nm, 341 nm, 372 nm) for 24 hours using a multi-wavelength irradiation spectrometer. The atropine content in the test formulation at each irradiation wavelength after irradiation was quantified using high-performance liquid chromatography, and the remaining percentage (%) was calculated. The remaining percentage (%) of atropine in the packaging materials of Examples 1 and 5 is shown in Table 5. The residual rate (%) is the percentage of the atropine content in the test preparation before irradiation, with that content set to 100%. 【0077】 The above test results demonstrate that using the various packaging materials of Examples 1 and 5 significantly improved the photostability of the 0.01% atropine aqueous solution when exposed to light of various irradiation wavelengths. 【0078】 Test Example 6: Confirmation of Light Transmittance of Various Packaging Materials In this test, the light transmittance of the packaging materials of Examples 1 to 6 and Examples 7 to 10 was measured at each irradiation wavelength to evaluate the light transmittance of the various packaging materials. The results of measuring the light transmittance of the various packaging materials at each wavelength are shown in Figures 1 and 2. Furthermore, Tables 6 and 7 show the wavelengths at which the light transmittance of the various packaging materials is 10% or less, 30% or less, 50% or less, 70% or less, 80% or less, and 90% or less. For example, in the case of the packaging material of Example 1, the wavelength at which the light transmittance is 30% or less is a wavelength less than 275 nm. Also, for example, in the case of the packaging material of Example 5, the wavelength at which the light transmittance is 80% or less is a wavelength less than 385 nm. 【0079】 【0080】 The above test results confirmed that the various packaging materials of Examples 1 to 6 suppressed the light transmittance of light rays in the 279 to 372 nm range to 80% or less, and that by containing an atropine-containing aqueous pharmaceutical composition in these materials, the photodegradation of atropine in the aqueous pharmaceutical composition could be suppressed. This result demonstrated that by using packaging materials that suppress the light transmittance of light rays in the wavelength range including these specific wavelengths to 80% or less, the photostability of atropine in the aqueous pharmaceutical composition can be ensured. Furthermore, the various packaging materials of Examples 7 to 10 suppressed the light transmittance of light rays in the 279 to 372 nm range to 15% or less, and it was confirmed that by containing an atropine-containing aqueous pharmaceutical composition in these materials, the photodegradation of atropine in the aqueous pharmaceutical composition could also be suppressed. 【0081】 The present invention provides an atropine-containing ophthalmic pharmaceutical formulation that exhibits excellent stability against light of a specific wavelength by housing the atropine-containing aqueous pharmaceutical composition in packaging that blocks light of a specific wavelength, and a method for stabilizing the same.

Claims

1. An ophthalmic pharmaceutical preparation comprising an aqueous pharmaceutical composition containing atropine or a salt thereof at a concentration of 0.001 to 0.1% (w / v), housed in a primary packaging that allows for internal visibility and blocks light rays with wavelengths of 210 to 380 nm.

2. The ophthalmic pharmaceutical preparation according to claim 1, wherein the primary packaging blocks light rays with wavelengths of 216 to 372 nm.

3. The ophthalmic pharmaceutical preparation according to claim 1, wherein the primary packaging blocks light rays with wavelengths of 279 to 372 nm.

4. An ophthalmic pharmaceutical preparation according to any one of claims 1 to 3, wherein the primary packaging has a light transmittance or average value of 80% or less for light with a wavelength of 279 to 372 nm.

5. The ophthalmic pharmaceutical preparation according to any one of claims 1 to 4, wherein the primary packaging is a plastic container.

6. The ophthalmic pharmaceutical preparation according to claim 5, wherein the plastic container is a polyethylene resin container, a polypropylene resin container, a polyethylene terephthalate resin container, or a cycloolefin resin container.

7. An ophthalmic pharmaceutical preparation according to any one of claims 1 to 6, wherein the primary packaging is contained within the secondary packaging.

8. The ophthalmic pharmaceutical preparation according to claim 7, wherein the secondary packaging is a label, a medicine bag, a cardboard box, or pillow packaging.

9. An ophthalmic pharmaceutical preparation comprising an aqueous pharmaceutical composition containing atropine or a salt thereof at a concentration of 0.001 to 0.1% (w / v), contained in a transparent plastic container, the plastic container being contained in packaging that blocks light rays with wavelengths of 210 to 380 nm, the packaging being a label, medicine bag, cardboard box, or pillow packaging.

10. The ophthalmic pharmaceutical preparation according to claim 9, wherein the packaging is a label, medicine bag, paper box, or pillow packaging that blocks light rays with wavelengths of 279 to 372 nm.

11. The ophthalmic pharmaceutical preparation according to claim 9 or 10, wherein the packaging is a label, medicine bag, paper box, or pillow packaging having a light transmittance or average value of 20% or less for light with wavelengths of 279 to 372 nm.

12. The ophthalmic pharmaceutical preparation according to any one of claims 1 to 11, wherein the aqueous pharmaceutical composition is an aqueous eye drop solution.

13. An ophthalmic pharmaceutical preparation according to any one of claims 1 to 12, wherein the concentration of atropine or a salt thereof is 0.01 to 0.025% (w / v).

14. An ophthalmic pharmaceutical preparation according to any one of claims 1 to 13, wherein atropine or a salt thereof is atropine sulfate or a hydrate thereof.

15. A method for photostabilizing atropine or a salt in an aqueous pharmaceutical composition, comprising the step of housing the aqueous pharmaceutical composition containing atropine or a salt thereof at a concentration of 0.001 to 0.1% (w / v) in a primary packaging that allows the interior to be seen and blocks light rays with a wavelength of 210 to 380 nm.

16. The method according to claim 15, wherein the primary packaging blocks light rays with wavelengths of 216 to 372 nm.

17. The method according to claim 15 or 16, wherein the primary packaging blocks light rays with wavelengths of 279 to 372 nm.

18. The method according to any one of claims 15 to 17, wherein the primary packaging material has a light transmittance or average value of 80% or less for light with a wavelength of 279 to 372 nm.

19. The method according to any one of claims 15 to 18, wherein the primary packaging is a plastic container.

20. The method according to claim 19, wherein the plastic container is a polyethylene resin container, a polypropylene resin container, a polyethylene terephthalate resin container, or a cycloolefin resin container.

21. The method according to any one of claims 15 to 20, further comprising the step of housing a primary package inside a secondary package.

22. The method according to claim 21, wherein the secondary packaging is a label, a medicine bag, a cardboard box, or pillow packaging.

23. A method for photostabilizing atropine or a salt in an aqueous pharmaceutical composition, comprising the steps of: housing an aqueous pharmaceutical composition containing atropine or a salt thereof at a concentration of 0.001 to 0.1% (w / v) in a plastic container whose interior is visible; and housing the plastic container in a packaging body that blocks light rays with wavelengths of 210 to 380 nm, wherein the packaging body is a label, a medicine bag, a paper box, or a pillow pack.

24. The method according to claim 23, wherein the packaging is a label, medicine bag, paper box, or pillow packaging that blocks light rays with wavelengths of 279 to 372 nm.

25. The method according to claim 23 or 24, wherein the packaging is a label, medicine bag, paper box, or pillow packaging having a light transmittance or average value of 20% or less for light with wavelengths of 279 to 372 nm.

26. The method according to any one of claims 15 to 25, wherein the aqueous pharmaceutical composition is an aqueous eye drop solution.

27. The method according to any one of claims 15 to 26, wherein the concentration of atropine or a salt thereof is 0.01 to 0.025% (w / v).

28. The method according to any one of claims 15 to 27, wherein atropine or a salt thereof is atropine sulfate or a hydrate thereof.

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