Atropine-containing aqueous pharmaceutical composition

Abstract

The present invention provides an aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine or a salt thereof in a concentration of 0.025% (w / v), wherein the aqueous pharmaceutical composition is administered to a myopic patient aged 12 to 15 years.

Description

ATROPINE-CONTAINING AQUEOUS PHARMACEUTICAL COMPOSITION

[0001] The present invention relates to an aqueous pharmaceutical composition comprising atropine or a salt thereof. Specifically, the present invention relates to an aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine or a salt thereof in a concentration of 0.025% (w / v), wherein the aqueous pharmaceutical composition is administered to a myopic patient aged 12 to 15 years. In addition, the present invention relates to an aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v), wherein the aqueous pharmaceutical composition is continuously administered to a myopic patient until the patient reaches 11 years of age or older.

[0002] Myopia is one form of ametropia, which is a pathology that the eyesight blurs because the parallel rays from far distance which enters eyes meets an image in front of the retina. Myopia is considered to be caused by that the image when seeing at a distance is focused not on the retina but in front of the retina in case that the refraction of the cornea or the lens is too strong (refractive myopia) or that the image when seeing at a distance is focused not on the retina but in front of the retina even though the thickness of the lens is reduced in case that the axial length (the length between the cornea and the retina) is extended and is too longer than normal (axial myopia).

[0003] In order to treat myopia, various treatments such as surgery, vision correction with glasses or contact lenses, and treatment with a drug have been carried out. Recently, the treatment with a drug, which is one of myopia treatments, has been actively studied, and some drugs which may suppress or prevent the myopia progression have been reported. It has been known that atropine is one of such drugs and has the property of suppressing the axial length prolongation. For example, Patent Document 1 discloses that an aqueous composition comprising 0.001 to 0.1 % (w / v) atropine or a salt thereof, a water-soluble polymer, and buffer (I), which is at a pH range of 6 or lower, has a potent action for suppressing the axial length prolongation and improving the refractive error without exacerbating the mydriatic action of atropine.

[0004] [PL 1] WO 2017 / 204262

[0005] It is said that myopia typically develops in school age and processes at a rate of about 0.5D (diopter) per year until 15 to 16 years. Also, the development and the rapid progression of myopia in early age may lead to high myopia in an adult with pathologic myopic lesions that cause visual impairment. Hence, in order to develop a medicament for producing the effect of improving myopia and the effect of suppressing myopia, it is very important to study a medicament for myopic patient in early age.

[0006] The present invention has been made in consideration of the above circumstances, and an object thereof is to find an atropine-containing aqueous pharmaceutical composition useful for the treatment of myopia, prevention of myopia and / or suppression of myopia. In addition, an object of the present invention is to suppress myopia progression spurred after discontinuation of the administration of an atropine-containing aqueous pharmaceutical composition.

[0007] The present inventors have intensively studied on an atropine-containing aqueous composition and consequently have found that when an aqueous composition comprising atropine or a salt thereof in a concentration of 0.025% (w / v) is administered to myopic patients aged 5 to 15 years, a change from spherical equivalent (SE) before administration of 0.00 diopter (D) or more can be surprisingly achieved even at 12 months after administration in myopic patients aged 12 to 15 years, and thus can produce higher effect of suppressing myopia. In addition, the present inventors have found that myopia progression may be spurred after discontinuation of the administration of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v), depending on the patient's age at the time of discontinuation, and that such myopia progression spurred can be suppressed by continuously administering the aqueous pharmaceutical composition to the patient until the patient reaches 11 years of age or older. Based upon the new findings, the present invention has been completed.

[0008] Specifically, the present invention provides the followings. (1) An aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine or a salt thereof in a concentration of 0.025% (w / v), wherein the aqueous pharmaceutical composition is administered to a myopic patient aged 12 to 15 years. (2) The aqueous pharmaceutical composition according to the above item (1), wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is improvement of refractive error. (3) The aqueous pharmaceutical composition according to the above item (1) or (2), wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from spherical equivalent (SE) before administration at 4 months after administration of 0.00 to +0.20 diopter (D). (4) The aqueous pharmaceutical composition according to the above item (1) or (2), wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from spherical equivalent (SE) before administration at 4 months after administration of 0.00 to +0.15 diopter (D). (5) The aqueous pharmaceutical composition according to the above item (1) or (2), wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from spherical equivalent (SE) before administration at 4 months after administration of 0.00 to +0.10 diopter (D). (6) The aqueous pharmaceutical composition according to the above item (1) or (2), wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from spherical equivalent (SE) before administration at 4 months after administration of 0.00 to +0.05 diopter (D). (7) The aqueous pharmaceutical composition according to any of the above items (3) to (6), wherein the change from spherical equivalent (SE) before administration is a change from spherical equivalent (SE) before administration at 8 months after administration. (8) The aqueous pharmaceutical composition according to any of the above items (3) to (6), wherein the change from spherical equivalent (SE) before administration is a change from spherical equivalent (SE) before administration at 12 months after administration. (9) The aqueous pharmaceutical composition according to the above item (1), wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is suppression of axial length prolongation. (10) The aqueous pharmaceutical composition according to any of the above items (1) to (9), wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from axial length before administration at 4 months after administration of -0.05 to 0.05 mm. (11) The aqueous pharmaceutical composition according to any of the above items (1) to (9), wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from axial length before administration at 4 months after administration of -0.03 to 0.03 mm. (12) The aqueous pharmaceutical composition according to any of the above items (1) to (9), wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from axial length before administration at 4 months after administration of -0.01 to 0.01 mm. (13) The aqueous pharmaceutical composition according to any of the above items (10) to (12), wherein the change from axial length before administration is a change from axial length before administration at 8 months after administration. (14) The aqueous pharmaceutical composition according to any of the above items (10) to (12), wherein the change from axial length before administration is a change from axial length before administration at 12 months after administration. (15) The aqueous pharmaceutical composition according to any of the above items (1) to (14), which does not substantially have mydriatic action. (16) The aqueous pharmaceutical composition according to any of the above items (1) to (15), wherein the aqueous pharmaceutical composition is administered ocularly in a dose of 1 drop per eye each time once a day. (17) The aqueous pharmaceutical composition according to the above item (16), wherein the aqueous pharmaceutical composition is administered ocularly before bedtime. (18) The aqueous pharmaceutical composition according to any of the above items (1) to (17), wherein the atropine or a salt thereof is atropine sulfate or a hydrate thereof. (19) The aqueous pharmaceutical composition according to any of the above items (1) to (18), which is an eye drop. (20) An aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine or a salt thereof in a concentration of 0.025% (w / v), wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is improvement of refractive error and the aqueous pharmaceutical composition is administered to a myopic patient aged 12 to 15 years in such a manner that the myopic patient achieves a change from spherical equivalent (SE) before administration at 4 months after administration of 0.00 to +0.20 diopter (D). (21) An aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine or a salt thereof in a concentration of 0.025% (w / v), wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is suppression of axial length prolongation and the aqueous pharmaceutical composition is administered to a myopic patient aged 12 to 15 years in such a manner that the myopic patient achieves a change from axial length before administration at 4 months after administration of -0.05 to 0.05 mm. (22) The aqueous pharmaceutical composition according to any of the above items (1) to (21), which is stored in a unit-dose container. (23) The aqueous pharmaceutical composition according to any of the above items (1) to (21), which is stored in a multi-dose container.

[0009] Each feature of the above items (1) to (23) may be optionally selected and combined two or more.

[0010] In addition, the present invention provides the followings. (24) A method of treating and / or preventing myopia, which comprises administering a therapeutically effective amount of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.025% (w / v) to a myopic patient aged 12 to 15 years in need thereof. (25) A method of suppressing myopia, which comprises administering a therapeutically effective amount of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.025% (w / v) to a myopic patient aged 12 to 15 years in need thereof. (26) A method of improving refractive error, which comprises administering a therapeutically effective amount of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.025% (w / v) to a myopic patient aged 12 to 15 years in need thereof. (27) A method of suppressing axial length prolongation, which comprises administering a therapeutically effective amount of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.025% (w / v) to a myopic patient aged 12 to 15 years in need thereof. (28) Use of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.025% (w / v) in the manufacture of a medicament for treating myopia for a myopic patient aged 12 to 15 years. (29) Use of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.025% (w / v) in the manufacture of a medicament for preventing myopia for a myopic patient aged 12 to 15 years. (30) Use of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.025% (w / v) in the manufacture of a medicament for suppressing myopia for a myopic patient aged 12 to 15 years. (31) An aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.025% (w / v) for use in treating myopia, preventing myopia and / or suppressing myopia, wherein the aqueous pharmaceutical composition is administered to a myopic patient aged 12 to 15 years. (32) An aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.025% (w / v) for use in improving refractive error, wherein the aqueous pharmaceutical composition is administered to a myopic patient aged 12 to 15 years. (33) An aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.025% (w / v) for use in suppressing axial length prolongation, wherein the aqueous pharmaceutical composition is administered to a myopic patient aged 12 to 15 years.

[0011] Each feature of the above items (1) to (33) may be optionally selected and combined two or more.

[0012] In addition, the present invention provides the followings. (A-1) An aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v), wherein the aqueous pharmaceutical composition is continuously administered to a myopic patient until the patient reaches 11 years of age or older. (A-2) An aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v), wherein the aqueous pharmaceutical composition is continuously administered to a myopic patient until the patient reaches 11 years of age or older to suppress myopia progression spurred after discontinuation of the administration. (A-3) The aqueous pharmaceutical composition according to the above item (A-1) or (A-2), wherein the aqueous pharmaceutical composition is continuously administered until the patient reaches 13 to 17 years of age. (A-4) The aqueous pharmaceutical composition according to the above item (A-1) or (A-2), wherein the aqueous pharmaceutical composition is continuously administered until the patient reaches older than 17 years of age. (A-5) The aqueous pharmaceutical composition according to any of the above items (A-1) to (A-4), wherein the myopic patient is a myopic patient aged 6 years or older. (A-6) The aqueous pharmaceutical composition according to any of the above items (A-1) to (A-4), wherein the myopic patient is a myopic patient aged 6 to 10 years. (A-7) The aqueous pharmaceutical composition according to any of the above items (A-1) to (A-4), wherein the myopic patient is a myopic patient aged 9 to 10 years. (A-8) The aqueous pharmaceutical composition according to the above item (A-3) or (A-4), wherein the myopic patient is a myopic patient aged 11 to 15 years. (A-9) The aqueous pharmaceutical composition according to any of the above items (A-1) to (A-8), wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is improvement of refractive error. (A-10) The aqueous pharmaceutical composition according to any of the above items (A-1) to (A-8), wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is suppression of axial length prolongation. (A-11) The aqueous pharmaceutical composition according to any of the above items (A-2) to (A-10), wherein the suppression of myopia progression spurred after discontinuation of the administration is suppression of refractive error progression spurred. (A-12) The aqueous pharmaceutical composition according to any of the above items (A-2) to (A-10), wherein the suppression of myopia progression spurred after discontinuation of the administration is suppression of axial length prolongation progression spurred. (A-13) The aqueous pharmaceutical composition according to any of the above items (A-1) to (A-12), wherein the concentration of atropine or a salt thereof is 0.01% (w / v). (A-14) The aqueous pharmaceutical composition according to any of the above items (A-1) to (A-12), wherein the concentration of atropine or a salt thereof is 0.025% (w / v). (A-15) The aqueous pharmaceutical composition according to any of the above items (A-1) to (A-14), which does not substantially have mydriatic action. (A-16) The aqueous pharmaceutical composition according to any of the above items (A-1) to (A-15), wherein the aqueous pharmaceutical composition is administered ocularly in a dose of 1 drop per eye each time once a day. (A-17) The aqueous pharmaceutical composition according to the above item (A-16), wherein the aqueous pharmaceutical composition is administered ocularly before bedtime. (A-18) The aqueous pharmaceutical composition according to any of the above items (A-1) to (A-17), wherein the atropine or a salt thereof is atropine sulfate or a hydrate thereof. (A-19) The aqueous pharmaceutical composition according to any of the above items (A-1) to (A-18), which is an eye drop. (A-20) The aqueous pharmaceutical composition according to any of the above items (A-1) to (A-19), which is stored in a unit-dose container. (A-21) The aqueous pharmaceutical composition according to any of the above items (A-1) to (A-19), which is stored in a multi-dose container.

[0013] Each feature of the above items (A-1) to (A-21) may be optionally selected and combined two or more.

[0014] In addition, the present invention provides the followings. (B-1) A method of treating and / or preventing myopia, which comprises continuously administering a therapeutically effective amount of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) to a myopic patient in need thereof until the patient reaches 11 years of age or older. (B-2) A method of treating and / or preventing myopia, which comprises continuously administering a therapeutically effective amount of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) to a myopic patient in need thereof until the patient reaches 11 years of age or older to suppress myopia progression spurred after discontinuation of the administration. (B-3) A method of suppressing myopia, which comprises continuously administering a therapeutically effective amount of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) to a myopic patient in need thereof until the patient reaches 11 years of age or older. (B-4) A method of suppressing myopia, which comprises continuously administering a therapeutically effective amount of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) to a myopic patient in need thereof until the patient reaches 11 years of age or older to suppress myopia progression spurred after discontinuation of the administration. (B-5) A method of improving refractive error, which comprises continuously administering a therapeutically effective amount of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) to a myopic patient in need thereof. (B-6) A method of improving refractive error, which comprises continuously administering a therapeutically effective amount of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) to a myopic patient in need thereof to suppress myopia progression spurred after discontinuation of the administration. (B-7) A method of suppressing axial length prolongation, which comprises continuously administering a therapeutically effective amount of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) to a myopic patient in need thereof. (B-8) A method of suppressing axial length prolongation, which comprises continuously administering a therapeutically effective amount of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) to a myopic patient in need thereof to suppress myopia progression spurred after discontinuation of the administration. (B-9) The method according to any of the above items (B-1) to (B-8), wherein the aqueous pharmaceutical composition is continuously administered until the patient reaches 13 to 17 years of age. (B-10) The method according to any of the above items (B-1) to (B-8), wherein the aqueous pharmaceutical composition is continuously administered until the patient reaches older than 17 years of age. (B-11) The method according to any of the above items (B-1) to (B-10), wherein the myopic patient is a myopic patient aged 6 years or older. (B-12) The method according to any of the above items (B-1) to (B-10), wherein the myopic patient is a myopic patient aged 6 to 10 years. (B-13) The method according to any of the above items (B-1) to (B-10), wherein the myopic patient is a myopic patient aged 9 to 10 years. (B-14) The method according to the above item (B-9) or (B-10), wherein the myopic patient is a myopic patient aged 11 to 15 years. (B-15) The method according to any of the above items (B-2), (B-4), (B-6), and (B-8) to (B-14), wherein the suppression of myopia progression spurred after discontinuation of the administration is suppression of refractive error progression. (B-16) The method according to any of the above items (B-2), (B-4), (B-6), and (B-8) to (B-14), wherein the suppression of myopia progression spurred after discontinuation of the administration is suppression of axial length prolongation progression. (B-17) The method according to any of the above items (B-1) to (B-16), wherein the concentration of atropine or a salt thereof is 0.01% (w / v). (B-18) The method according to any of the above items (B-1) to (B-16), wherein the concentration of atropine or a salt thereof is 0.025% (w / v). (B-19) The method according to any of the above items (B-1) to (B-18), wherein the aqueous pharmaceutical composition does not substantially have mydriatic action. (B-20) The method according to any of the above items (B-1) to (B-19), wherein the aqueous pharmaceutical composition is administered ocularly in a dose of 1 drop per eye each time once a day. (B-21) The method according to the above item (B-19), wherein the aqueous pharmaceutical composition is administered ocularly before bedtime. (B-22) The method according to any of the above items (B-1) to (B-21), wherein the atropine or a salt thereof is atropine sulfate or a hydrate thereof. (B-23) The method according to any of the above items (B-1) to (B-22), wherein the aqueous pharmaceutical composition is an eye drop. (B-24) The method according to any of the above items (B-1) to (B-23), wherein the aqueous pharmaceutical composition is stored in a unit-dose container. (B-25) The method according to any of the above items (B-1) to (B-23), wherein the aqueous pharmaceutical composition is stored in a multi-dose container.

[0015] Each feature of the above items (B-1) to (B-25) may be optionally selected and combined two or more.

[0016] In addition, the present invention provides the followings. (C-1) Use of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) in the manufacture of a medicament for treating myopia continuously administered to a myopic patient until the patient reaches 11 years of age or older. (C-2) Use of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) in the manufacture of a medicament for treating myopia continuously administered to a myopic patient until the patient reaches 11 years of age or older to suppress myopia progression spurred after discontinuation of the administration. (C-3) Use of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) in the manufacture of a medicament for preventing myopia continuously administered to a myopic patient until the patient reaches 11 years of age or older. (C-4) Use of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) in the manufacture of a medicament for preventing myopia continuously administered to a myopic patient until the patient reaches 11 years of age or older to suppress myopia progression spurred after discontinuation of the administration. (C-5) Use of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) in the manufacture of a medicament for suppressing myopia continuously administered to a myopic patient until the patient reaches 11 years of age or older. (C-6) Use of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) in the manufacture of a medicament for suppressing myopia continuously administered to a myopic patient until the patient reaches 11 years of age or older to suppress myopia progression spurred after discontinuation of the administration. (C-7) The use according to any of the above items (C-1) to (C-6), wherein the medicament is continuously administered until the patient reaches 13 to 17 years of age. (C-8) The use according to any of the above items (C-1) to (C-6), wherein the medicament is continuously administered until the patient reaches older than 17 years of age. (C-9) The use according to any of the above items (C-1) to (C-8), wherein the myopic patient is a myopic patient aged 6 years or older. (C-10) The use according to any of the above items (C-1) to (C-8), wherein the myopic patient is a myopic patient aged 6 to 10 years. (C-11) The use according to any of the above items (C-1) to (C-8), wherein the myopic patient is a myopic patient aged 9 to 10 years. (C-12) The use according to the above item (C-7) or (C-8), wherein the myopic patient is a myopic patient aged 11 to 15 years. (C-13) The use according to any of the above items (C-2), (C-4), and (C-6) to (C-12), wherein the suppression of myopia progression spurred after discontinuation of the administration is suppression of refractive error progression. (C-14) The use according to any of the above items (C-2), (C-4), and (C-6) to (C-12), wherein the suppression of myopia progression spurred after discontinuation of the administration is suppression of axial length prolongation progression. (C-15) The use according to any of the above items (C-1) to (C-14), wherein the concentration of atropine or a salt thereof is 0.01% (w / v). (C-16) The use according to any of the above items (C-1) to (C-14), wherein the concentration of atropine or a salt thereof is 0.025% (w / v). (C-17) The use according to any of the above items (C-1) to (C-16), wherein the medicament does not substantially have mydriatic action. (C-18) The use according to any of the above items (C-1) to (C-17), wherein the medicament is administered ocularly in a dose of 1 drop per eye each time once a day. (C-19) The use according to the above item (C-18), wherein the medicament is administered ocularly before bedtime. (C-20) The use according to any of the above items (C-1) to (C-19), wherein the atropine or a salt thereof is atropine sulfate or a hydrate thereof. (C-21) The use according to any of the above items (C-1) to (C-20), wherein the medicament is an eye drop. (C-22) The use according to any of the above items (C-1) to (C-21), wherein the medicament is stored in a unit-dose container. (C-23) The use according to any of the above items (C-1) to (C-21), wherein the medicament is stored in a multi-dose container.

[0017] Each feature of the above items (C-1) to (C-23) may be optionally selected and combined two or more.

[0018] In addition, the present invention provides the followings. (D-1) An aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) for use in the treatment of myopia, prevention of myopia and / or suppression of myopia, wherein the aqueous pharmaceutical composition is continuously administered to a myopic patient until the patient reaches 11 years of age or older. (D-2) An aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) for use in the treatment of myopia, prevention of myopia and / or suppression of myopia, wherein the aqueous pharmaceutical composition is continuously administered to a myopic patient until the patient reaches 11 years of age or older to suppress myopia progression spurred after discontinuation of the administration. (D-3) An aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) for use in the improvement of refractive error, wherein the aqueous pharmaceutical composition is continuously administered to a myopic patient until the patient reaches 11 years of age or older. (D-4) An aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) for use in the improvement of refractive error, wherein the aqueous pharmaceutical composition is continuously administered to a myopic patient until the patient reaches 11 years of age or older to suppress myopia progression spurred after discontinuation of the administration. (D-5) An aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) for use in the suppression of axial length prolongation, wherein the aqueous pharmaceutical composition is continuously administered to a myopic patient until the patient reaches 11 years or age or older. (D-6) An aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) for use in the suppression of axial length prolongation, wherein the aqueous pharmaceutical composition is continuously administered to a myopic patient until the patient reaches 11 years of age or older to suppress myopia progression spurred after discontinuation of the administration. (D-7) The aqueous pharmaceutical composition according to any of the above items (D-1) to (D-6), wherein the aqueous pharmaceutical composition is continuously administered until the patient reaches 13 to 17 years of age. (D-8) The aqueous pharmaceutical composition according to any of the above items (D-1) to (D-6), wherein the aqueous pharmaceutical composition is continuously administered until the patient reaches older than 17 years of age. (D-9) The aqueous pharmaceutical composition according to any of the above items (D-1) to (D-8), wherein the myopic patient is a myopic patient aged 6 years or older. (D-10) The aqueous pharmaceutical composition according to any of the above items (D-1) to (D-8), wherein the myopic patient is a myopic patient aged 6 to 10 years. (D-11) The aqueous pharmaceutical composition according to any of the above items (D-1) to (D-8), wherein the myopic patient is a myopic patient aged 9 to 10 years. (D-12) The aqueous pharmaceutical composition according to the above item (D-7) or (D-8), wherein the myopic patient is a myopic patient aged 11 to 15 years. (D-13) The aqueous pharmaceutical composition according to any of the above items (D-2), (D-4), and (D-6) to (D-12), wherein the suppression of myopia progression spurred after discontinuation of the administration is suppression of refractive error progression. (D-14) The aqueous pharmaceutical composition according to any of the above items (D-2), (D-4), and (D-6) to (D-12), wherein the suppression of myopia progression spurred after discontinuation of the administration is suppression of axial length prolongation progression. (D-15) The aqueous pharmaceutical composition according to any of the above items (D-1) to (D-14), wherein the concentration of atropine or a salt thereof is 0.01% (w / v). (D-16) The aqueous pharmaceutical composition according to any of the above items (D-1) to (D-14), wherein the concentration of atropine or a salt thereof is 0.025% (w / v). (D-17) The aqueous pharmaceutical composition according to any of the above items (D-1) to (D-16), which does not substantially have mydriatic action. (D-18) The aqueous pharmaceutical composition according to any of the above items (D-1) to (D-17), wherein the aqueous pharmaceutical composition is administered ocularly in a dose of 1 drop per eye each time once a day. (D-19) The aqueous pharmaceutical composition according to the above item (D-18), wherein the aqueous pharmaceutical composition is administered ocularly before bedtime. (D-20) The aqueous pharmaceutical composition according to any of the above items (D-1) to (D-19), wherein the atropine or a salt thereof is atropine sulfate or a hydrate thereof. (D-21) The aqueous pharmaceutical composition according to any of the above items (D-1) to (D-20), which is an eye drop. (D-22) The aqueous pharmaceutical composition according to any of the above items (D-1) to (D-21), which is stored in a unit-dose container. (D-23) The aqueous pharmaceutical composition according to any of the above items (D-1) to (D-21), which is stored in a multi-dose container.

[0019] Each feature of the above items (D-1) to (D-23) may be optionally selected and combined two or more.

[0020] In addition, the present invention provides the followings. (E-1) An aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v), wherein the aqueous pharmaceutical composition is administered to a myopic patient aged 13 to 16 years. (E-2) The aqueous pharmaceutical composition according to the above item (E-1), wherein the myopic patient is a myopic patient who has previously received a pharmaceutical composition comprising atropine or a salt thereof. (E-3) The aqueous pharmaceutical composition according to the above item (E-1), wherein the myopic patient is a myopic patient who has previously received an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v). (E-4) The aqueous pharmaceutical composition according to the above item (E-1), wherein the myopic patient is a myopic patient who has previously received an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) ocularly. (E-5) The aqueous pharmaceutical composition according to the above item (E-1), wherein the myopic patient is a myopic patient who has previously received an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) ocularly for 12 months. (E-6) The aqueous pharmaceutical composition according to the above item (E-1), wherein the myopic patient is a myopic patient who has previously received an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) ocularly in a dose of 1 drop per eye each time once a day for 12 months. (E-7) The aqueous pharmaceutical composition according to any of the above items (E-2) to (E-6), wherein the myopic patient is a myopic patient whose age at the time of a previous administration of the pharmaceutical composition or the aqueous pharmaceutical composition is 12 to 15 years. (E-8) The aqueous pharmaceutical composition according to any of the above items (E-1) to (E-7), wherein the concentration of atropine or a salt thereof is 0.01% (w / v). (E-9) The aqueous pharmaceutical composition according to any of the above items (E-1) to (E-7), wherein the concentration of atropine or a salt thereof is 0.025% (w / v). (E-10) The aqueous pharmaceutical composition according to any of the above items (E-2) to (E-9), wherein the concentration of atropine or a salt thereof in the previously-administered pharmaceutical composition or aqueous pharmaceutical composition is 0.01% (w / v). (E-11) The aqueous pharmaceutical composition according to any of the above items (E-2) to (E-9), wherein the concentration of atropine or a salt thereof in the previously-administered pharmaceutical composition or aqueous pharmaceutical composition is 0.025% (w / v). (E-12) The aqueous pharmaceutical composition according to any of the above items (E-1) to (E-11), wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is improvement of refractive error. (E-13) The aqueous pharmaceutical composition according to any of the above items (E-1) to (E-11), wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is suppression of axial length prolongation. (E-14) The aqueous pharmaceutical composition according to any of the above items (E-1) to (E-13), which does not substantially have mydriatic action. (E-15) The aqueous pharmaceutical composition according to any of the above items (E-1) to (E-14), wherein the aqueous pharmaceutical composition is administered ocularly in a dose of 1 drop per eye each time once a day. (E-16) The aqueous pharmaceutical composition according to the above item (E-15), wherein the aqueous pharmaceutical composition is administered ocularly before bedtime. (E-17) The aqueous pharmaceutical composition according to any of the above items (E-1) to (E-16), wherein the atropine or a salt thereof is atropine sulfate or a hydrate thereof. (E-18) The aqueous pharmaceutical composition according to any of the above items (E-1) to (E-17), which is an eye drop. (E-19) The aqueous pharmaceutical composition according to any of the above items (E-1) to (E-18), which is stored in a unit-dose container. (E-20) The aqueous pharmaceutical composition according to any of the above items (E-1) to (E-18), which is stored in a multi-dose container.

[0021] Each feature of the above items (E-1) to (E-20) may be optionally selected and combined two or more.

[0022] In addition, the present invention provides the followings. (F-1) An aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v), wherein the aqueous pharmaceutical composition is administered to a myopic patient who has previously received a pharmaceutical composition comprising atropine or a salt thereof. (F-2) The aqueous pharmaceutical composition according to the above item (F-1), wherein the myopic patient is a myopic patient whose age at the time of a previous administration of the pharmaceutical composition comprising atropine or a salt thereof is 12 to 15 years. (F-3) The aqueous pharmaceutical composition according to the above item (F-1) or (F-2), wherein the myopic patient is a myopic patient who has previously received an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v). (F-4) The aqueous pharmaceutical composition according to the above item (F-1) or (F-2), wherein the myopic patient is a myopic patient who has previously received an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) ocularly. (F-5) The aqueous pharmaceutical composition according to the above item (F-1) or (F-2), wherein the myopic patient is a myopic patient who has previously received an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) ocularly for 12 months. (F-6) The aqueous pharmaceutical composition according to the above item (F-1) or (F-2), wherein the myopic patient is a myopic patient who has previously received an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) ocularly in a dose of 1 drop per eye each time once a day for 12 months. (F-7) The aqueous pharmaceutical composition according to any of the above items (F-1) to (F-6), wherein the concentration of atropine or a salt thereof is 0.01% (w / v). (F-8) The aqueous pharmaceutical composition according to any of the above items (F-1) to (F-6), wherein the concentration of atropine or a salt thereof is 0.025% (w / v). (F-9) The aqueous pharmaceutical composition according to any of the above items (F-1) to (F-8), wherein the concentration of atropine or a salt thereof in the previously-administered pharmaceutical composition or aqueous pharmaceutical composition is 0.01% (w / v). (F-10) The aqueous pharmaceutical composition according to any of the above items (F-1) to (F-8), wherein the concentration of atropine or a salt thereof in the previously-administered pharmaceutical composition or aqueous pharmaceutical composition is 0.025% (w / v). (F-11) The aqueous pharmaceutical composition according to any of the above items (F-1) to (F-10), wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is improvement of refractive error. (F-12) The aqueous pharmaceutical composition according to any of the above items (F-1) to (F-10), wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is suppression of axial length prolongation. (F-13) The aqueous pharmaceutical composition according to any of the above items (F-1) to (F-12), which does not substantially have mydriatic action. (F-14) The aqueous pharmaceutical composition according to any of the above items (F-1) to (F-13), wherein the aqueous pharmaceutical composition is administered ocularly in a dose of 1 drop per eye each time once a day. (F-15) The aqueous pharmaceutical composition according to the above item (F-14), wherein the aqueous pharmaceutical composition is administered ocularly before bedtime. (F-16) The aqueous pharmaceutical composition according to any of the above items (F-1) to (F-15), wherein the atropine or a salt thereof is atropine sulfate or a hydrate thereof. (F-17) The aqueous pharmaceutical composition according to any of the above items (F-1) to (F-16), which is an eye drop. (F-18) The aqueous pharmaceutical composition according to any of the above items (F-1) to (F-17), which is stored in a unit-dose container. (F-19) The aqueous pharmaceutical composition according to any of the above items (F-1) to (F-17), which is stored in a multi-dose container. (F-20) An aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine sulfate or a hydrate thereof in a concentration of 0.01% (w / v), wherein the aqueous pharmaceutical composition is administered ocularly to a myopic patient in a dose of 1 drop per eye each time once a day before bedtime, and wherein the myopic patient is a myopic patient who has previously received an aqueous pharmaceutical composition comprising atropine sulfate or a hydrate thereof in a concentration of 0.01% (w / v) ocularly in a dose of 1 drop per eye each time once a day for 12 months at 12 to 15 years of age. (F-21) An aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine sulfate or a hydrate thereof in a concentration of 0.025% (w / v), wherein the aqueous pharmaceutical composition is administered ocularly to a myopic patient in a dose of 1 drop per eye each time once a day before bedtime, and wherein the myopic patient is a myopic patient who has previously received an aqueous pharmaceutical composition comprising atropine sulfate or a hydrate thereof in a concentration of 0.025% (w / v) ocularly in a dose of 1 drop per eye each time once a day for 12 months at 12 to 15 years of age.

[0023] Each feature of the above items (F-1) to (F-21) may be optionally selected and combined two or more.

[0024] According to the present invention, a medicament for treating myopia, preventing myopia and / or suppressing myopia for a myopic patient aged 12 to 15 years can be provided. More specifically, the application of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.025% (w / v) to a myopic patient aged 12 to 15 years achieves a change from spherical equivalent (SE) before administration of 0.00 diopter (D) or more even at 12 months after administration, and thus can improve refractive error and produce higher effect of suppressing myopia. In addition, according to the present invention, the continuous administration of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) to a myopic patient until the patient reaches 11 years of age or older can suppress myopia progression spurred even after discontinuation of the administration of the aqueous pharmaceutical composition.

[0025] Hereinafter, the present invention is illustrated in detail.

[0026] The aqueous pharmaceutical composition of the present invention comprises "atropine or a salt thereof" as an active ingredient.

[0027] As used herein, the term "atropine or a salt thereof" also includes (i) a hydrate of atropine or a salt thereof, (ii) an organic solvate of atropine or a salt thereof, and (iii) a combination of the hydrate and the organic solvate.

[0028] The salt of atropine includes, for example, atropine sulfate or a hydrate thereof. The salt of atropine is preferably atropine sulfate hydrate. Atropine sulfate hydrate is a compound represented by the following structural formula:

[0029] In a case where the atropine or the salt thereof includes a crystal polymorph and a group of crystal polymorphs (crystal polymorph system), those crystal polymorph and group of crystal polymorphs (crystal polymorph system) are also encompassed by the scope of the present invention. Here, the group of crystal polymorphs (crystal polymorph system) means not only individual crystal forms obtained at respective stages where crystals transform into various forms depending on conditions and states during the manufacture, crystallization, storage, and the like of the crystals, but also a mixture of the crystal forms obtained at two or more of the stages.

[0030] Atropine or a salt thereof may be manufactured according to a commonly-used method in the field of organic synthetic chemistry or may alternatively be a commercially available product. For example, atropine sulfate hydrate is a commercially available product from Tokyo Chemical Industry Co., Ltd. (product code: A0550).

[0031] In the aqueous pharmaceutical composition of the present invention, the amount of atropine or a salt thereof is preferably 0.01% or 0.025% (w / v). As used herein, the term "% (w / v)" means the mass (g) of an object ingredient in 100 mL of the aqueous pharmaceutical composition of the present invention. When the aqueous pharmaceutical composition of the present invention comprises a salt of atropine, the value means the amount of the salt of atropine. In addition, when the aqueous pharmaceutical composition of the present invention comprises atropine or a salt thereof in the form of a hydrate or a solvate, the value means the amount of atropine or a salt thereof in the form of a hydrate or a solvate. Hereinafter, the same shall apply to the followings unless otherwise specified.

[0032] As used herein, the terms "aqueous pharmaceutical composition" and "aqueous composition" means a composition comprising water as a solvent. The amount of water in the aqueous pharmaceutical composition of the present invention is not particularly limited, but is preferably 10% (w / v) or more, more preferably 30% (w / v) or more, and furthermore preferably 50% (w / v) or more, relative to the total amount of the aqueous pharmaceutical composition. In particular, the amount thereof is preferably 70% (w / v) or more, more preferably 90% (w / v) or more, and furthermore preferably 95% (w / v) or more, relative to the total amount of the aqueous pharmaceutical composition.

[0033] As used herein, the term "myopia" is defined as a refractive state of an uncorrected eye where parallel rays meet the eye in front of the retina. The "myopia" as used herein includes all and every known classification and definition of myopia including, for example, refractive myopia, axial myopia, pseudomyopia, pathological myopia, simple myopia, extreme myopia, severe myopia, high myopia, moderate myopia, low myopia, myopia complicated by glaucoma (particularly, juvenile glaucoma), myopia at the risk of the onset of glaucoma development, and myopia with high intraocular pressure, preferably refractive myopia, axial myopia, extreme myopia, severe myopia, high myopia, and myopia complicated by glaucoma (particularly, juvenile glaucoma), more preferably refractive myopia and axial myopia, and furthermore preferably axial myopia.

[0034] As used herein, the term "treatment (treating)" means every treatment of myopia or the associated symptoms, for example, treating or improving myopia, particularly refractive myopia and / or axial myopia and alleviating or inhibiting symptoms associated with myopia. The treatment also encompasses inhibiting recurrence of myopia. As used herein, the term "prevention (preventing)" means preventing the myopia development, delaying the myopia development, or reducing the risk of the myopia development. As used herein, the term "suppression of myopia (suppressing myopia)" means delaying the myopia progression (delay of myopia progression) or reducing the myopia progression (reduction of myopia progression). Also, the term "treating myopia, preventing myopia and / or suppressing myopia" as used herein includes suppressing the axial length prolongation and / or improving or suppressing the refractive error.

[0035] The "myopic patient" in the present invention may be a patient immediately after the myopia development, a patient less than 1 year after the myopia development, a patient between 1 to 5 years after the myopia development or a patient 5 years or more after the myopia development, but the period from the myopia development is not particularly limited. The "myopic patient" in the present invention is preferably a myopic patient aged 12 to 15 years. The myopic patient's age at the time of administration of the aqueous pharmaceutical composition of the present invention is not particularly limited as long as the effect of treating myopia, preventing myopia, and / or suppressing myopia is achieved. The myopic patient's age at the time of administration of the aqueous pharmaceutical composition of the present invention may be, for example, 5 to 19 years, 5 to 17 years, 5 to 15 years, 6 to 15 years, 6 to 10 years, 9 to 10 years, 5 to 7 years, 8 to 9 years, 10 to 11 years, 12 to 15 years, 6 to 8 years, 11 to 15 years, or 13 to 16 years. Also, the myopic patient's age at the time of administration of the aqueous pharmaceutical composition of the present invention may be, for example, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 11 years, 12 years, 13 years, 14 years, 15 years, 16 years, 17 years, 18 years, or 19 years. When the aqueous pharmaceutical composition of the present invention is administered to a myopic patient aged 20 years or older, the necessity of administration can be determined based on appropriately monitoring the myopia progression.

[0036] As used herein, the term "therapeutically effective amount" means an amount for producing the therapeutic effect on myopia or the associated symptoms or an amount for delaying the myopia development or the myopia progression, relative to untreated subjects.

[0037] As used herein, the "change from spherical equivalent (SE) before administration" refers to the spherical equivalent (D) changed from the spherical equivalent (D) before administration of the aqueous pharmaceutical composition of the present invention used as a standard at each time point after administration. Here, the term "spherical equivalent (SE)" means the power value obtained by converting half of cylindrical power to spherical power so that the position of the circle of least confusion is kept. In the present invention, the change from spherical equivalent (SE) before administration is preferably 0.00 diopter (D) or more. For example, the change from spherical equivalent (SE) before administration at 4 months after administration may be 0.00 to +0.20 diopter (D), preferably 0.00 to +0.15 diopter (D), more preferably 0.00 to +0.10 diopter (D), and particularly preferably 0.00 to +0.05 diopter (D). Said change from spherical equivalent (SE) before administration may be a change from spherical equivalent (SE) before administration at 8 months after administration and a change from spherical equivalent (SE) before administration at 12 months after administration.

[0038] As used herein, the "change from axial length before administration" refers to the axial length (mm) prolongated or shortened from the axial length (mm) before administration of the aqueous pharmaceutical composition of the present invention used as a standard at each time point after administration. In the present invention, the change from axial length before administration is preferably 0 mm or less. For example, the change from axial length before administration at 4 months after administration may be -0.05 to 0.05mm, preferably -0.03 to 0.03mm, and more preferably -0.01 to 0.01 mm. Said change from axial length before administration may be a change from axial length before administration at 8 months after administration and a change from axial length before administration at 12 months after administration.

[0039] As used herein, the term "not substantially have mydriatic action" means that the aqueous pharmaceutical composition does not have mydriatic action at the level that affects daily life. The term includes that the aqueous pharmaceutical composition has no mydriatic action. In addition, even if mydriatic action is found in any measuring way, it is interpreted as "not substantially have mydriatic action" when the treated patient does not experience visual side effects of glare and pupil dilation which affect daily life.

[0040] The aqueous pharmaceutical composition of the present invention may comprise a pharmaceutically acceptable active ingredient other than atropine or a salt thereof unless otherwise specified.

[0041] The aqueous pharmaceutical composition of the present invention may comprise a pharmaceutically acceptable additive as appropriate. For example, a water-soluble polymer, a buffering agent, a tonicity agent, a preservative, a stabilizing agent, a surfactant, a pH adjuster, and the like can be added as the pharmaceutically acceptable additive. They may be used alone, respectively, and two or more thereof may be used in combination. Also, they may be added in an appropriate amount.

[0042] The aqueous pharmaceutical composition of the present invention can contain a water-soluble polymer available as a pharmaceutical additive as appropriate. Examples of the water-soluble polymer include celluloses and their derivatives (e.g., methyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, carboxymethylethyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl cellulose, cellulose acetate phthalate, ethyl cellulose, hydroxymethyl cellulose, hydroxyethylmethyl cellulose, hypromellose acetate succinate and hypromellose phthalate); synthetic polymers (e.g., polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinylacetal diethylamino acetate, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, and carboxyvinyl polymer); naturally-occurring polymers or saccharides (e.g., gum arabic, sodium alginate, alginic acid propylene glycol ester, agar, gelatin, tragacanth, and xanthan gum); and the like.

[0043] When the aqueous pharmaceutical composition of the present invention contains a water-soluble polymer, the amount of the water-soluble polymer can be suitably varied depending on, for example, the type of the water-soluble polymer, but is preferably 0.01 to 5% (w / v) and more preferably 0.1 to 2% (w / v). Also, when the aqueous pharmaceutical composition of the present invention contains a water-soluble polymer, the water-soluble polymer may be used alone or two or more thereof may be used in combination.

[0044] The aqueous pharmaceutical composition of the present invention can contain a buffering agent available as a pharmaceutical additive as appropriate. Examples of the buffering agent include a phosphate buffer, a citrate buffer, a borate buffer, a carbonate buffer, an acetate buffer, a tartrate buffer, an aminocarboxylate buffer, trometamol, and the like.

[0045] When the aqueous pharmaceutical composition of the present invention contains a buffering agent, the amount of the buffering agent can be suitably varied depending on, for example, the type of the buffering agent, but is preferably 0.001 to 10% (w / v), more preferably 0.01 to 5% (w / v), furthermore 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 the most preferably 0.01 to 0.1% (w / v). Also, when the aqueous pharmaceutical composition of the present invention contains a buffering agent, the buffering agent may be used alone or two or more thereof may be used in combination.

[0046] In the present invention, the phosphate buffer can be derived from any pharmaceutically acceptable phosphate buffer. Examples of the phosphate buffer include phosphoric acid; phosphates such as alkali metal phosphates, alkaline earth metal phosphates; hydrates thereof; and the like. Specific examples thereof include sodium hydrogen phosphate hydrate, sodium dihydrogen phosphate (also referred to as "monosodium phosphate"), sodium dihydrogen phosphate monohydrate, sodium dihydrogen phosphate dihydrate (also referred to as "sodium dihydrogen phosphate hydrate"), potassium dihydrogen phosphate (also referred to as "monopotassium phosphate"), sodium hydrogen phosphate heptahydrate, trisodium phosphate, dipotassium phosphate, and the like.

[0047] When the aqueous pharmaceutical composition of the present invention contains a phosphate buffer, the amount of the phosphate buffer can be suitably varied depending on, for example, the type of the phosphate buffer, but is preferably 0.01 to 1.0% (w / v), more preferably 0.05 to 1.0% (w / v), and furthermore preferably 0.05 to 0.5% (w / v).

[0048] In the present invention, the citrate buffer can be derived from any pharmaceutically acceptable citrate buffer. Examples of the citrate buffer include citric acid; citrates such as alkali metal citrates and alkaline earth metal citrates; hydrates thereof; and the like. Specific examples thereof include citric acid hydrate, sodium citrate, sodium citrate hydrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, and the like.

[0049] When the aqueous pharmaceutical composition of the present invention contains a citrate buffer, the amount of the citrate buffer can be suitably varied depending on, for example, the type of the citrate buffer, but is preferably 0.001 to 1.0% (w / v), more preferably 0.005 to 0.5% (w / v), furthermore preferably 0.01 to 0.1% (w / v), even more preferably 0.01 to 0.05% (w / v), and particularly preferably 0.02 to 0.04% (w / v).

[0050] In the present invention, the borate buffer can be derived from any pharmaceutically acceptable borate buffer. Examples of the borate buffer include boric acid or a salt thereof, borax, and the like. Specific examples thereof include boric acid, sodium borate, potassium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, and the like.

[0051] In the present invention, the carbonate buffer can be derived from any pharmaceutically acceptable carbonate buffer. Examples of the carbonate buffer include carbonic acid or a salt thereof and the like. Specific examples thereof include carbonic acid, sodium hydrogen carbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium hydrogen carbonate, magnesium carbonate, and the like.

[0052] In the present invention, the citrate buffer can be derived from any pharmaceutically acceptable citrate buffer. Examples of the citrate buffer include acetic acid or a salt thereof and the like. Specific examples thereof include acetic acid, ammonium acetate, potassium acetate, calcium acetate, sodium acetate, and the like.

[0053] In the present invention, the tartrate buffer can be derived from any pharmaceutically acceptable tartrate buffer. Examples of the tartrate buffer include tartaric acid or a salt thereof and the like. Specific examples include sodium tartrate, potassium tartrate, and the like.

[0054] In the present invention, the aminocarboxylate buffer includes, for example, an aspartate buffer, a glutamate buffer, ε-aminocaproic acid, and the like. Examples of the aspartate buffer include aspartic acid or a salt thereof and the like. Specific examples thereof include sodium aspartate, magnesium aspartate, and the like. Examples of the glutamate buffer include glutamic acid or a salt thereof and the like. Specific examples thereof include sodium glutamate, potassium glutamate, and the like.

[0055] The aqueous pharmaceutical composition of the present invention can contain a tonicity agent available as a pharmaceutical additive as appropriate. Examples of the tonicity agent include an ionic tonicity agent, a non-ionic tonicity agent, and the like.

[0056] Examples of the ionic tonicity agent include sodium chloride, potassium chloride, calcium chloride, magnesium chloride, and the like. Examples of the non-ionic tonicity agent include glycerin (concentrated glycerin), mannitol, propylene glycol, polyethylene glycol, glucose, sorbitol, xylitol, trehalose, and like.

[0057] When the aqueous pharmaceutical composition of the present invention contains a tonicity agent, the amount of the tonicity agent can be suitably varied depending on, for example, the type of the tonicity agent, but is preferably 0.01 to 10% (w / v), more preferably 0.05 to 5% (w / v), furthermore preferably 0.1 to 5% (w / v), even more preferably 0.5 to 5% (w / v), and particularly preferably 1 to 5% (w / v). Also, when the aqueous pharmaceutical composition of the present invention contains a tonicity agent, the tonicity agent may be used alone or two or more thereof may be used in combination.

[0058] The aqueous pharmaceutical composition of the present invention can contain a preservative available as a pharmaceutical additive as appropriate. Examples of the preservative include benzalkonium chloride, benzalkonium bromide, benzethonium chloride, chlorhexidine gluconate, chlorhexidine hydrochloride, parabens (e.g., methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate), sodium chlorite, phenoxyethanol, sorbic acid, chlorobutanol, and the like.

[0059] When the aqueous pharmaceutical composition of the present invention contains a preservative, the amount of the preservative can be suitably varied depending on, for example, the type of the preservative. The amount thereof is, for example, 0.001 to 1% (w / v). Also, when the aqueous pharmaceutical composition of the present invention contains a preservative, the preservative may be used alone or two or more thereof may be used in combination.

[0060] The aqueous pharmaceutical composition of the present invention can contain a stabilizing agent available as a pharmaceutical additive as appropriate. Examples of the stabilizing agent include edetic acid or a salt thereof, cyclodextrin, and the like. They may be in the form of a hydrate or a solvate. Examples of the salt of edetic acid include disodium edetate (also referred to as "sodium edetate"), tetrasodium edetate, and the like. When the aqueous pharmaceutical composition of the present invention contains a stabilizing agent, the amount of the stabilizing agent can be suitably varied depending on, for example, the type of the stabilizing agent. The amount thereof is, for example, 0.01 to 1% (w / v), but is not limited thereto if the stabilizing agent has an effect other than the effect as stabilizing agent. Also, when the aqueous pharmaceutical composition of the present invention contains a stabilizing agent, the stabilizing agent may be used alone or two or more thereof may be used in combination.

[0061] The aqueous pharmaceutical composition of the present invention can contain a surfactant available as a pharmaceutical additive as appropriate. Examples of the surfactant include polyoxyethylene sorbitan monooleate, polyoxyl 40 stearate, polyoxyethylene hydrogenated castor oil, and the like. When the aqueous pharmaceutical composition of the present invention contains a surfactant, the amount of the surfactant can be suitably varied depending on, for example, the type of the surfactant. The amount thereof is, for example, 0.01 to 1% (w / v). Also, when the aqueous pharmaceutical composition of the present invention contains a surfactant, the surfactant may be used alone or two or more thereof may be used in combination.

[0062] The aqueous pharmaceutical composition of the present invention can contain a pH adjuster available as a pharmaceutical additive as appropriate. The pH adjuster is, for example, an acid or a base. Examples of the acid include hydrochloric acid, phosphoric acid, acetic acid, citric acid, and the like. Examples of the base include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, and the like.

[0063] The pH of the aqueous pharmaceutical composition in the present invention is not limited to a specific value, provided that it falls within a medicinally acceptable range. The pH of the aqueous pharmaceutical composition in the present invention is preferably in a range of 6 or less, more preferably in a range of 4 to 6, furthermore preferably in a range of 4 to 5, and particularly preferably about 4 or 5. The pH of the aqueous pharmaceutical composition in the present invention may be, for example, 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, or 6.0. Also, when the aqueous pharmaceutical composition of the present invention comprises a pH adjuster, the pH adjuster may be used alone or two or more thereof may be used in combination.

[0064] The aqueous pharmaceutical composition of the present invention is preferably used as an eye drop, particularly an ophthalmic aqueous solution.

[0065] The dosage and administration of the aqueous pharmaceutical composition administered in the present invention are not limited as long as it can sufficiently provide a desired efficacy, The aqueous pharmaceutical composition of the present invention may be administered ocularly, preferably in a dose of 1 to 3 drops each time at a frequency of 1 to 5 times a day, more preferably in a dose of 1 to 2 drops each time at a frequency of 2 to 4 times a day, and the most preferably in a dose of 1 drop once a day before bedtime.

[0066] As used herein, the term "unit-dose container" means a container for eye drop in which a cap is tightly attached to the bottle mouth with fusion, which is opened by breaking the fused part between the cap and the bottle mouth when it is used. The unit-dose container may contain just one dose of the aqueous pharmaceutical composition for one shot, or more doses thereof used several times in one day.

[0067] As used herein, the term "multiple-dose container" means a container for eye drop equipped with a bottle body and a cap which can be fixed to the bottle body, said cap can be freely opened and closed. The multiple-dose container generally contains plural doses of the aqueous pharmaceutical composition for using for a certain period.

[0068] The aqueous pharmaceutical composition of the present invention can be stored in a unit-dose container or a multiple-dose container. Unless the aqueous pharmaceutical composition of the present invention substantially comprises a preservative such as benzalkonium chloride, it is preferable that the aqueous pharmaceutical composition is stored in a unit-dose container.

[0069] Further, the osmotic pressure of the aqueous pharmaceutical composition in the present invention is not limited to a specific value, provided that it falls within a range acceptable to a living body. The osmotic pressure of the aqueous pharmaceutical composition in the present invention is, for example, 100 to 1000 mOsm, preferably 200 to 500 mOsm, and more preferably 250 to 350 mOsm. In general, the osmotic pressure of an aqueous composition is more than a little affected by the amounts of medicinal substance and additive in the aqueous pharmaceutical composition. In the present invention, the osmotic pressure can be adjusted to fall within the above-described ranges by appropriately adjusting the amounts of those substances that can affect the osmotic pressure. It should be noted that the osmotic pressure of the aqueous pharmaceutical composition in the present invention can be measured by a common method. For example, the osmotic pressure of the aqueous pharmaceutical composition in the present invention can be measured in accordance with the method described in the "Osmometry (Osmolarity Determination)" section of the Japanese Pharmacopoeia, 18th Revised Edition.

[0070] Preferably, the aqueous pharmaceutical composition of the present invention is continuously administered to suppress myopia progression spurred after discontinuation of the administration. In particular, it is desirable to continuously administer the aqueous pharmaceutical composition of the present invention until the late teenage years, when the myopia progression is stabilized, because rapid progression of myopia may occur after discontinuation of the administration. Also, it is preferable to continuously administer the aqueous pharmaceutical composition of the present invention until 11 years of age or older, more preferably from 13 to 17 years of age, furthermore preferably until 17 years of age or older. Also, since myopia progression may occur until the late teenage years, it is preferable to continuously administer the aqueous pharmaceutical composition of the present invention to a patient until the patient reaches the late teenage years or 20 years of age after the start of administration. The continuously-administered myopic patient's age may be, for example, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 11 years, 12 years, 13 years, 14 years, 15 years, 16 years, 17 years, 18 years, or 19 years. When the aqueous pharmaceutical composition of the present invention is administered to a myopic patient aged 20 years or older, the necessity of administration can be determined based on appropriately monitoring the myopia progression.

[0071] The aqueous pharmaceutical composition of the present invention may be administered to a myopic patient who has previously received a pharmaceutical composition comprising atropine or a salt thereof or the aqueous pharmaceutical composition of the present invention. For example, the aqueous pharmaceutical composition of the present invention may be administered to a myopic patient aged 13 to 16 years who has previously received a pharmaceutical composition comprising atropine or a salt thereof or an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) for a certain period (e.g., 12 months). In the present invention, the administration of the aqueous pharmaceutical composition of the present invention to a myopic patient may be carried out after a certain period (for example, several days, several weeks or several months) has elapsed following discontinuation of the administration of a pharmaceutical composition comprising atropine or a salt thereof or an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) or immediately after such discontinuation.

[0072] Typical examples of the formulation using the aqueous pharmaceutical composition of the present invention are shown below, but the present invention is not limited to only the following Formulation Examples. The amount of each ingredient formulated in the following formulation examples (% (w / v)) is the amount (g) in 100 mL of the aqueous pharmaceutical composition.

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[0075]

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[0080]

[0081] Hereinafter, the present invention is illustrated in Examples in order to make it easy to understand the present invention. The present invention, however, is not intended to be limited thereto by any means.

[0082] Example 1: Effect of atropine-containing aqueous composition on myopic patients aged 5 to 15 years (spherical equivalent (SE)) According to the following procedures, the changes from spherical equivalent (SE) before administration of placebo and atropine-containing aqueous composition after the administration were calculated to evaluate the effect of atropine-containing aqueous composition for myopic patients aged 5 to 15 years.

[0083] (Preparation of Sample) Atropine sulfate hydrate (0.1 mg), sodium dihydrogen phosphate dihydrate, sodium citrate hydrate, concentrated glycerin and hydroxyethyl cellulose were dissolved in purified water, pH adjuster (dilute hydrochloric acid and / or sodium hydroxide) and purified water were added so that the solution was brought to a total amount of 1 mL to prepare 0.01% atropine-containing aqueous composition. Also, atropine sulfate hydrate (0.25 mg), sodium dihydrogen phosphate dihydrate, sodium citrate hydrate, concentrated glycerin and hydroxyethyl cellulose were dissolved in purified water, pH adjuster (dilute hydrochloric acid and / or sodium hydroxide) and purified water were added so that the solution was brought to a total amount of 1 mL to prepare 0.025% atropine-containing aqueous composition. In addition, sodium dihydrogen phosphate dihydrate, sodium citrate hydrate, concentrated glycerin and hydroxyethyl cellulose were dissolved in purified water, pH adjuster (dilute hydrochloric acid and / or sodium hydroxide) and purified water were added so that the solution was brought to a total amount of 1 mL to prepare an aqueous composition free of atropine sulfate hydrate as placebo (control).

[0084] (Test Method) The test subjects were patients aged 5 to 15 years diagnosed with myopia in both eyes. Placebo, 0.01% atropine-containing aqueous composition or 0.025% atropine-containing aqueous composition was administered ocularly to both eyes of each patient in a dose of 1 drop each time once day (before bedtime) for 24 months.

[0085] (Evaluation Method) Cyplegin(registered trademark)1% ophthalmic solution was administered ocularly to each patient twice at 5-minute intervals to make the eyes the cycloplegia state. The eyes were checked for the cycloplegia state 45 minutes after the last ocular administration. When it was judged that the cycloplegia state of the patient was not sufficient, Cyplegin(registered trademark)1% ophthalmic solution was administered ocularly to the patient once more. The spherical power, cylindrical power and cylindrical axis angle for both eyes of each patient under the cycloplegia state were then measured 5 times using an autorefractometer. The values when the minimum and maximum values of 5 measured values each of cylindrical powder and cylindrical axis angle for both eyes are within 0.50 D were used. The spherical equivalent of each group was calculated from the spherical powers and cylindrical powers measured 5 time for both eyes according to the following formula and the mean value of spherical equivalent was calculated. The measurement of spherical equivalent was performed every 4 months after administration.Calculation Formula: Spherical Equivalent (D) = Spherical Power + Cylindrical Power x 1 / 2

[0086] (Test Results) The mean values of spherical equivalent (D) for each age group in the placebo administration group, the 0.01% atropine-containing aqueous composition administration group and the 0.025% atropine-containing aqueous composition administration group are shown in Table 9.

[0087] As shown in Table 9, a change from spherical equivalent (SE) before administration at 4 months after administration of 0.00 diopter (D) or more was achieved in patients aged 10 to 15 years of 0.025% atropine-containing aqueous composition administration group. As a result, the improvement of refractive error was observed. In patients aged 10 to 15 years of 0.025% atropine-containing aqueous composition administration group, the improvement of refractive error was observed even at 12 months after administration. Hence, it was suggested that 0.025% atropine-containing aqueous composition would produce higher effect of suppressing myopia, especially for myopic patients aged 12 to 15 years.

[0088] Example 2: Effect of atropine-containing aqueous composition on myopic patients aged 5 to 15 years (axial length) According to the following procedures, the changes from axial length before administration of placebo and atropine-containing aqueous composition after the administration were calculated to evaluate the effect of atropine-containing aqueous composition for myopic patients aged 5 to 15 years.

[0089] (Preparation of Sample) According to the similar procedure to the (Preparation of Sample) of Example 1, 0.01% atropine-containing aqueous composition, 0.025% atropine-containing aqueous composition and placebo were prepared.

[0090] (Test Method) According to the similar procedure to the (Test Method) of Example 1, the test was performed.

[0091] (Evaluation Method) Cyplegin(registered trademark)1% ophthalmic solution was administered ocularly to each patient twice at 5-minute intervals to make the eyes the cycloplegia state. The eyes were checked for the cycloplegia state 45 minutes after the last ocular administration. When it was judged that the cycloplegia state of the patient was not sufficient, Cyplegin(registered trademark)1% ophthalmic solution was administered ocularly to the patient once more. The axial length for both eyes of each patient under the cycloplegia state was measured using an optical axial length measurement device. The measurement of axial length was performed every 4 months after administration.

[0092] (Test Results) The mean values of axial length (mm) for each age group in the placebo administration group, the 0.01% atropine-containing aqueous composition administration group and the 0.025% atropine-containing aqueous composition administration group are shown in Table 10.

[0093] As shown in Table 10, the suppression of axial length prolongation was observed in the atropine-containing aqueous composition administration groups. In patients aged 12 to 15 years of 0.025% atropine-containing aqueous composition administration group, no axial length prolongation was observed at 4 months after administration. Hence, it was suggested that 0.025% atropine-containing aqueous composition would produce higher effect of suppressing myopia, especially for myopic patients aged 12 to 15 years.

[0094] Example 3: Effect observed upon discontinuation of administration of atropine-containing aqueous composition to myopic patients aged 6 to 15 years for 2 years (spherical equivalent (SE)) The effect of the spherical equivalent (SE) was evaluated when 0.01% atropine-containing aqueous composition or 0.025% atropine-containing aqueous composition is administered for 2 years followed by it is switched to placebo, for each age group in each treatment group.

[0095] (Preparation of Sample), (Evaluation Method), and (Evaluation Method) were performed in the same manner as the above Example 1. The change in spherical equivalent (SE) was calculated from the spherical equivalent (SE) values upon discontinuation of the administration of atropine-containing aqueous composition (after two years of the initial administration) and at one year after the discontinuation (after three years of the initial administration). Each age group is based on the patient age upon discontinuation of the administration of atropine-containing aqueous composition.

[0096] (Test Results) The changes in spherical equivalent (SE) (diopter (D)) for each age group in the placebo administration group, the 0.01% atropine-containing aqueous composition administration group and the 0.025% atropine-containing aqueous composition administration group are shown in Table 11.

[0097] As shown in Table 11, the changes in spherical equivalent (SE) when 0.01% atropine-containing aqueous composition or 0.025% atropine-containing aqueous composition was switched to placebo tended to be greater than that in the placebo administration group. In particular, in the 0.025% atropine-containing aqueous composition administration group, it was found that patients aged 8 to 10 years were more affected by administration discontinuation than patients aged 11 to 12 years and 13 to 17 years. As a result, it was suggested that it was preferable to continuously administer 0.025% atropine-containing aqueous composition until the patients reach 11 years of age or older, when the change in spherical equivalent (SE) becomes smaller. Then, it was observed that it was more preferable to continuously administer 0.025% atropine-containing aqueous composition until the patients reach 13 to 17 years of age, when the change in spherical equivalent (SE) becomes further smaller. Also, a similar trend was observed in the 0.01% atropine-containing aqueous composition administration group. Then, it was observed that it was preferable to continuously administer 0.01% atropine-containing aqueous composition until the patients reach 11 years of age or older, when the change in spherical equivalent (SE) becomes smaller, and it was more preferable to continuously administer 0.01% atropine-containing aqueous composition until the patients reach 13 to 17 years of age, when the change in spherical equivalent (SE) becomes further smaller.

[0098] Example 4: Effect observed upon discontinuation of administration of atropine-containing aqueous composition to myopic patients aged 6 to 15 years for 2 years (axial length) The effect of the axial length was evaluated when 0.01% atropine-containing aqueous composition or 0.025% atropine-containing aqueous composition is administered for 2 years followed by it is switched to placebo, for each age group in each treatment group.

[0099] (Preparation of Sample), (Evaluation Method), and (Evaluation Method) were performed in the same manner as the above Example 2. The change in axial length was calculated from the axial length values upon discontinuation of the administration of atropine-containing aqueous composition (after two years of the initial administration) and at one year after discontinuation (after three years of the initial administration). Each age group is based on the patient age upon discontinuation of the administration of atropine-containing aqueous composition.

[0100] (Test Results) The changes in axial length (mm) for each age group in the placebo administration group, the 0.01% atropine-containing aqueous composition administration group and the 0.025% atropine-containing aqueous composition administration group are shown in Table 12.

[0101] As shown in Table 12, the changes in axial length (mm) when 0.01% atropine-containing aqueous composition or 0.025% atropine-containing aqueous composition was switched to placebo tended to be greater than that in the placebo administration group. In particular, in the 0.01% atropine-containing aqueous composition administration group, it was found that the patients aged 8 to 10 years were more affected by administration discontinuation than the patients aged 11 to 12 years and 13 to 17 years. As a result, it was suggested that it was preferable to continuously administer 0.01% atropine-containing aqueous composition until the patients reach 11 years of age or older, when the change in axial length (mm) becomes smaller. Then, it was observed that it was more preferable to continuously administer 0.01% atropine-containing aqueous composition until the patients reach 13 to 17 years of age, when the change in axial length (mm) becomes further smaller. Also, a similar trend was observed in the 0.025% atropine-containing aqueous composition administration group. Then, it was observed that it was preferable to continuously administer 0.025% atropine-containing aqueous composition until the patients reach 11 years of age or older, when the change in axial length (mm) becomes smaller, and it was more preferable to continuously administer 0.025% atropine-containing aqueous composition until the patients reach 13 to 17 years of age, when the change in axial length (mm) becomes further smaller.

[0102] According to the present invention, a medicament for treating myopia, preventing myopia and / or suppressing myopia for a myopic patient aged 12 to 15 years can be provided. More specifically, the application of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.025% (w / v) to a myopic patient aged 12 to 15 years achieves a change from spherical equivalent (SE) before administration of 0.00 diopter (D) or more even at 12 months after administration, and thus can improve refractive error and produce higher effect of suppressing myopia. In addition, according to the present invention, the continuous administration of an aqueous pharmaceutical composition comprising atropine or a salt thereof in a concentration of 0.01% or 0.025% (w / v) to a myopic patient until the patient reaches 11 years of age or older can suppress myopia progression spurred even after discontinuation of the administration of the aqueous pharmaceutical composition.

Claims

1. An aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine or a salt thereof in a concentration of 0.025% (w / v), wherein the aqueous pharmaceutical composition is administered to a myopic patient aged 12 to 15 years.

2. The aqueous pharmaceutical composition according to claim 1, wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is improvement of refractive error.

3. The aqueous pharmaceutical composition according to claim 1 or 2, wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from spherical equivalent (SE) before administration at 4 months after administration of 0.00 to +0.20 diopter (D).

4. The aqueous pharmaceutical composition according to claim 1 or 2, wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from spherical equivalent (SE) before administration at 4 months after administration of 0.00 to +0.15 diopter (D).

5. The aqueous pharmaceutical composition according to claim 1 or 2, wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from spherical equivalent (SE) before administration at 4 months after administration of 0.00 to +0.10 diopter (D).

6. The aqueous pharmaceutical composition according to claim 1 or 2, wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from spherical equivalent (SE) before administration at 4 months after administration of 0.00 to +0.05 diopter (D).

7. The aqueous pharmaceutical composition according to any one of claims 3 to 6, wherein the change from spherical equivalent (SE) before administration is a change from spherical equivalent (SE) before administration at 8 months after administration.

8. The aqueous pharmaceutical composition according to any one of claims 3 to 6, wherein the change from spherical equivalent (SE) before administration is a change from spherical equivalent (SE) before administration at 12 months after administration.

9. The aqueous pharmaceutical composition according to claim 1, wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is suppression of axial length prolongation.

10. The aqueous pharmaceutical composition according to any one of claims 1 to 9, wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from axial length before administration at 4 months after administration of -0.05 to 0.05 mm.

11. The aqueous pharmaceutical composition according to any one of claims 1 to 9, wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from axial length before administration at 4 months after administration of -0.03 to 0.03 mm.

12. The aqueous pharmaceutical composition according to any one of claims 1 to 9, wherein the aqueous pharmaceutical composition is used in such a manner that the myopic patient achieves a change from axial length before administration at 4 months after administration of -0.01 to 0.01 mm.

13. The aqueous pharmaceutical composition according to any one of claims 10 to 12, wherein the change from axial length before administration is a change from axial length before administration at 8 months after administration.

14. The aqueous pharmaceutical composition according to any one of claims 10 to 12, wherein the change from axial length before administration is a change from axial length before administration at 12 months after administration.

15. The aqueous pharmaceutical composition according to any one of claims 1 to 14, which does not substantially have mydriatic action.

16. The aqueous pharmaceutical composition according to any one of claims 1 to 15, wherein the aqueous pharmaceutical composition is administered ocularly in a dose of 1 drop per eye each time once a day.

17. The aqueous pharmaceutical composition according to claim 16, wherein the aqueous pharmaceutical composition is administered ocularly before bedtime.

18. The aqueous pharmaceutical composition according to any one of claims 1 to 17, wherein the atropine or a salt thereof is atropine sulfate or a hydrate thereof.

19. The aqueous pharmaceutical composition according to any one of claims 1 to 18, which is an eye drop.

20. An aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine or a salt thereof in a concentration of 0.025% (w / v), wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is improvement of refractive error and the aqueous pharmaceutical composition is administered to a myopic patient aged 12 to 15 years in such a manner that the myopic patient achieves a change from spherical equivalent (SE) before administration at 4 months after administration of 0.00 to +0.20 diopter (D).

21. An aqueous pharmaceutical composition for the treatment of myopia, prevention of myopia and / or suppression of myopia, comprising atropine or a salt thereof in a concentration of 0.025% (w / v), wherein the treatment of myopia, prevention of myopia and / or suppression of myopia is suppression of axial length prolongation and the aqueous pharmaceutical composition is administered to a myopic patient aged 12 to 15 years in such a manner that the myopic patient achieves a change from axial length before administration at 4 months after administration of -0.05 to 0.05 mm.

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