TW201838629A - Agent for preventing myopia, treating myopia, and/or preventing myopia progression comprising umeclidinium as active ingredient - Google Patents

Abstract

The present invention relates to an agent for preventing myopia, treating myopia, and/or preventing myopia progression, comprising umeclidinium as an active ingredient.

Description

 Medicament containing indigo ammonium as active ingredient for preventing myopia, treating myopia and/or preventing myopia growth  

The present invention relates generally to an agent for preventing myopia, treating myopia and/or preventing the growth of myopia, which comprises umeclidinium as an active ingredient.

Myopia is a form of refractive error, which is a pathology in which the light from a long distance entering the eye is imaged in front of the retina and the vision is blurred. In the case where the refractive power of the cornea/crystal is too strong, when the person looks at a long distance, the image is not focused on the retina, but is focused on the front of the retina. This type of myopia is called refractive myopia. On the other hand, in the case where the length of the axial length between the cornea and the retina is elongated, that is, the length is longer than the normal length, when the person looks at a long distance, the image is not focused on the retina. Instead, focus on the retina, even if the thickness of the crystal is reduced. This type of myopia is called axial myopia. The development of myopia at a young age or the rapid growth of myopia may lead to high myopia in adults and pathological myopia with visual disability. In order to prevent myopia, treat myopia, and/or prevent the growth of myopia, various studies based on surgery, optical wear, or drugs have been tried.

Atropine is known as its sulfate hydrate form as shown below, and it has a preventive effect on myopia growth by reducing axial elongation (Patent Document 1). However, atropine has a significant dose-related dilation effect, which may result in unacceptable glare and photophobia, loss of depth of focus, and possibly more UV light into the eye. Atropine also reduces normal vision adjustment in a dose-dependent manner, which can result in poor near vision. These side effects are reduced by the clinical effect of using high concentrations of atropine in the clinical setting, although low doses of atropine have been shown to be effective in reducing axial elongation, but have less dilation and loss of vision modulation.

At the same time, guanidine, especially umeclidinium bromide (hereinafter, "deuterium bromide" may also be referred to simply as "ammonium sulphate"), is a compound represented by the following chemical formula, which has been inhaled. A powder sold by ENCRUSE ^(TM ), which alleviates various symptoms based on obstructive airway disorders in chronic obstructive pulmonary disease (COPD).

Patent Document 2 discloses a pharmaceutical combination comprising indole bromide and a corticosteroid for the treatment of COPD and asthma. However, the effect of topical administration of indole on the eye has not been reported, particularly regarding its effect of preventing myopia, treating myopia, and/or preventing myopia growth.

 [Previous Technical Literature]    [Patent Literature]  

[Patent Document 1] WO 2012/161655

[Patent Document 2] WO 2012/168161

It is an object of the present invention to find a novel compound useful for preventing myopia, treating myopia and/or preventing myopia growth. Furthermore, it is an object of the present invention to find a novel compound which has side effects for preventing myopia, treating myopia and/or preventing myopia growth and having a reduced cause of mydriasis.

The inventors of the present invention have conducted intensive studies to solve the above problems, and have found that guanidine, which is used for the treatment of chronic obstructive pulmonary disease (COPD), can inhibit the elongation of the axial length of the eye. Therefore, the sulphate is used for preventing myopia, treating myopia, and / or prevent myopia growth. Further, the present inventors have also found that guanidine has an effect of suppressing the elongation of the axial length even at a dose far lower than that of atropine, and further has a lower side effect of atropine than atropine. The present invention has been completed based on these new findings.

The invention is applicable to the following.

(Item 1) An agent for preventing myopia, treating myopia, and/or preventing the growth of myopia, comprising indigo or a salt thereof as an active ingredient.

(Item 2) The agent of item 1, wherein the agent has substantially no dilation effect.

(Item 3) The agent according to Item 1 or 2, wherein the concentration of indole or a salt thereof is from about 0.000001 to about 5% (w/v).

(Item 4) The agent according to Item 1 or 2, wherein the concentration of indole or a salt thereof is from about 0.00001 to about 2% (w/v).

(Item 5) The agent according to Item 1 or 2, wherein the concentration of indole or a salt thereof is from about 0.0001 to about 2% (w/v).

(Item 6) The agent according to Item 1 or 2, wherein the concentration of indoxy ammonium or a salt thereof is from about 0.001 to about 2% (w/v).

(Item 7) The agent according to Item 1 or 2, wherein the concentration of indole or a salt thereof is from about 0.001 to about 0.2% (w/v).

(Item 8) The agent according to any one of items 1 to 7, which is for topical administration to the eye.

(Item 9) The agent of item 8, wherein the topical administration of the eye is instillation administration or intravitreal administration.

(Item 10) The agent according to any one of items 1 to 9, which is formulated as an eye drop, an ophthalmic gel, an ophthalmic ointment or an injection.

(Item 11) The agent according to any one of items 1 to 10, wherein the indigoside or a salt thereof is indole bromide.

(Item 12) An agent for suppressing elongation of the length of the axial axis, which comprises guanidine or a salt thereof as an active ingredient.

(Item 13) Use of guanidine or a salt thereof for the manufacture of a medicament for preventing myopia, treating myopia, and/or preventing myopia growth.

(Item 14) A guanidine or a salt thereof for preventing myopia, treating myopia, and/or preventing myopia from growing.

(Item 15) A pharmaceutical composition comprising indole or a salt thereof for use in preventing myopia, treating myopia, and/or preventing myopia growth.

(Item 16) A method of preventing myopia, treating myopia, and/or preventing the growth of myopia, comprising administering a therapeutically effective amount of guanidine or a salt thereof to a mammal in need thereof.

As shown by the experimental results described below, it has been confirmed that valdecylamine can inhibit the axial length elongation more strongly than atropine. Therefore, indigo is considered to be a more potent agent for preventing myopia, treating myopia, and/or preventing myopia growth as a more potent than atropine. In addition, it has also been confirmed that sulphate has an effect of inhibiting the elongation of the axial length even at a dose far lower than that of atropine, and further has a lower side effect than that of atropine, and thus it is desired that valdomin becomes a practical agent. It is used to prevent myopia, treat myopia and/or prevent myopia growth, and has reduced side effects that interfere with daily life caused by dilation and loss of vision regulation.

Some specific embodiments of the invention are described in detail below.

As used herein, "an agent for preventing myopia, treating myopia, and/or preventing the growth of myopia" contains indole or a salt thereof as an active ingredient.

As used herein, "salt ammonium salt" is not limited as long as it is a salt having a pharmaceutically acceptable anion. For example, the salt includes: a salt having a hydroxide ion; a salt having an inorganic acid anion such as nitrate, sulfate, and phosphate; having, for example, acetate, fumarate, maleate, succinate, citrate, Tartrate, adipic acid, gluconate, glucoheptonate, glucuronide, terephthalate, mesylate, lactate, hippurate, 1,2-ethanedisulfonate, hydroxy Isothionate, lactobionate, oleate, pamoate, polygalacturonate, stearate, citrate, triflate, benzene sulfonate, p-toluene a salt of an organic acid anion of an acid radical, a lauryl sulfate, a methyl sulfate, a naphthalenesulfonate, and a sulfosalicylate; and a salt having a halogen ion such as a bromide ion, a fluoride ion, a chloride ion, and an iodide ion. In the present invention, a particularly preferred salt of indole is a salt having a bromide ion.

The chemical name of "deuterium bromide" is 1-[2-(benzyloxy)ethyl]-4-(hydroxydiphenylmethyl)-1-nitrogen cation bicyclo[2.2.2]octane bromide. (1-[2-(benzyloxy)ethyl]-4-(hydroxydiphenylmethyl)-1-azoniabicyclo [2.2.2] octane bromide), the chemical structure of which is shown below.

Further, "ammonium or a salt thereof" may be in the form of a hydrate or a solvate.

When "deuterium or its salt" is a geometric isomer or an optical isomer, the present invention encompasses such isomers. Further, when "valium bromide or a salt thereof" has a proton tautomer, the present invention also encompasses such a tautomer or a salt thereof.

When "deuterium or its salt" has a polymorphism and a polymorphic group (homogeneous polymorphic system), the present invention also encompasses this isomorphic polymorph and polymorph (polymorphic system). As used herein, a homogeneous polymorphic group (homogeneous polymorphic system) means a crystalline form at each stage and throughout the process as the crystal form changes with conditions and conditions of preparation, crystallization, storage, and the like.

"Deuteroline or its salt" can be prepared in a conventional manner; or it can be obtained as a commercially available product. For example, indole bromide is commercially available from MedChem express (product code: HY-12100).

The concentration of "ammonium or a salt thereof" used herein is not particularly limited, but in the case of an eye drop, it may be, for example, 0.000001 to 5% (w/v), and 0.00001-2% (w/v). ), preferably 0.0001 to 2% (w/v), 0.001 to 2% (w/v), and 0.0001 to 1% (w/v), more preferably 0.0001 to 0.2% (w/v), and 0.001 to 0.2% (w/v), more preferably 0.0001 to 0.1% (w/v), particularly preferably 0.0001 to 0.01% (w/v).

The concentration of "ammonium or its salt" as used herein may mean the concentration of the free form of indigo, or the concentration of its salt.

The term "substantially does not have a dilated effect" in the present invention means that the agent does not have a dilating effect that interferes with the degree of daily life. Therefore, even if the dilated effect is found in any measurement manner, when the treated patient does not experience the visual side effects of glare and pupil dilation that interferes with his/her daily life, it is interpreted as "substantially no dilated effect".

In the present invention, "myopia" is defined as the refractive state of an uncorrected eye that the light system meets before the retina of the eye. "Myopia" in the present invention includes all and every known classification and definition of myopia, including axial myopia, refractive myopia, pathological myopia, simple myopia, and very severe myopia ( Extreme myopia), severe myopia, strong myopia, moderate myopia, and light myopia.

As used herein, "agents for preventing myopia, treating myopia, and/or preventing myopia growth" include agents for preventing refractive myopia, treating refractive myopia, and/or preventing the growth of refractive myopia, and for preventing The agent for axial myopia, for treating axial myopia, and/or for preventing the growth of axial myopia is preferably an agent for preventing axial myopia, treating axial myopia, and/or preventing the growth of axial myopia. The term "prevention of myopia growth" as used herein may mean slowing myopia growth or reducing myopia growth. The term "preventing myopia" as used herein may mean preventing the onset of myopia or delaying the onset of myopia.

As shown in the results of the experiment described below, indigoside can inhibit the elongation of the axial length of the eye, and thus the present invention can also include an agent for inhibiting the elongation of the length of the axial axis, which comprises indigo or a salt thereof as an active ingredient.

In the present invention, "desalidom or its salt" is preferably used for preventing myopia, treating myopia and/or preventing myopia growth, and particularly preferably for preventing myopia in school-age children or preventing adolescents with myopia growth or Myopia in adults, and/or prevention of myopia in school-age children, or prevention of myopia growth in adolescents or adults with myopia growth.

In the present invention, the "agent for preventing myopia, treating myopia and/or preventing the growth of myopia" may be used depending on the dosage form, the severity of the symptoms, the age, the age of onset of onset, the myopia of the parents, the weight of the patient in need thereof, the judgment of the physician, etc. And change. In the case of eye drops, the agent can be administered in an eye drop, for example, in the following manner: daily to weekly, preferably daily; in an amount of 1 to 5 drops each time, preferably 1 time each time - 3 drops, more preferably 1 to 2 drops each time, and even more preferably 1 drop per time; frequency of 1-4 times a day, preferably 1-3 times a day, more preferably once or twice a day Times, especially good once a day. Preferably, it is administered once a day, one drop at a time, and is administered daily with an eye drop.

In the present invention, indigoside may be administered topically, orally or parenterally, and the administration method includes: topical administration of the eye including continuous and continuous delivery to the eye (instillation administration, administration of ophthalmic ointment, Conjunctival sac administration, intravitreal administration, subconjunctival administration, Tenon capsule administration, etc.; oral administration; intravenous administration; and transdermal administration.

Preferred formulations for topical administration of indigo to the eye include eye drops, ophthalmic gels and ophthalmic ointments, and injections thereof can also be used for such administration, particularly for subconjunctival administration, An injection for administration to the sac or intravitreal injection. The present formulation comprising indole ammonium as the active ingredient can be prepared by forming the pharmaceutically acceptable additive as necessary, by forming it into a dosage form suitable for administration.

In the present invention, dosage forms suitable for oral administration include, for example, tablets, capsules, granules, and powders, and dosage forms suitable for parenteral administration include, for example, injections, eye drops, ophthalmic gels, ophthalmic ointments, and patches. , gel and intercalating agent. These dosage forms can be prepared in the general manner widely used in the art.

In order for the therapeutic effect of the present invention to continue more effectively, DDS formulations, such as formulations for intraocular implants and microspheres, can be used.

The eyedrops can be prepared, as needed, with some optional additives selected from, for example, tonicity agents, buffers, surfactants, stabilizers, preservatives, and the like. The pH of the eye drop is not limited as long as the pH is within the acceptable range of the ophthalmic formulation, and is usually preferably in the range of 2-8. Tension agents include, for example, sodium chloride. Buffering agents include, for example, sodium phosphate and sodium acetate. Surfactants include, for example, polyoxyethylene sorbitan monooleate, polyoxyl 40 stearate, and polyoxyethylene hydrogenated castor oil. Stabilizers include, for example, sodium citrate and disodium edetate. Preservatives include, for example, benzalkonium chloride and paraben.

When the formulation of the present invention containing indigo as an active ingredient is an eye drop, an ophthalmic gel or an ophthalmic ointment, the formulation may or may not contain a preservative.

Ophthalmic ointments can be prepared from widely used base materials such as white petrolatum and liquid paraffin.

If desired, the tablet can be prepared with some optional additives selected from, for example, excipients, disintegrating agents, binders, lubricants, coating agents, flavoring agents, and the like. Excipients include, for example, lactose, dextrose, D-mannitol, anhydrous calcium hydrogen phosphate, starch, and sucrose. Disintegrators include, for example, carboxymethylcellulose, calcium carboxymethylcellulose, croscarmellose sodium, cross-linked polyvinylpyrrolidone, starch, partially pregelatinized starch, and low Replace hydroxypropyl cellulose. Binders include, for example, hydroxypropyl cellulose, ethyl cellulose, gum arabic, starch, partially pregelatinized starch, polyvinylpyrrolidone, and polyvinyl alcohol. Lubricants include, for example, magnesium stearate, calcium stearate, talc, hydrated cerium oxide, and hydrogenated oils. The coating agent includes, for example, purified sucrose, hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, and polyvinylpyrrolidone. Flavoring agents include, for example, citric acid, aspartame, ascorbic acid, and menthol.

The injection can be prepared, if necessary, with some optional additives selected from, for example, tonicity agents, buffers, surfactants, thickeners, and the like. Tension agents include, for example, sodium chloride. Buffering agents include, for example, sodium phosphate. Surfactants include, for example, polyoxyethylene sorbitan monooleate. Thickeners include, for example, methylcellulose.

For example, the obtained powder can be compacted by mixing and grinding the terpene ammonium and biodegradable polymers such as hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxyvinyl polymer and polyacrylic acid. To prepare an intercalator. Excipients, binders, stabilizers, and/or pH adjusting agents may be used therein, as appropriate.

For example, formulations for intraocular implants can be biodegradable polymers such as polylactic acid, polyglycolate, lactide-glycolate copolymer, and hydroxypropyl fibers. It has been prepared.

When the terpene ammonium is administered topically to the eye in the form of an eye drop, it is preferred that the eye drop agent does not substantially cause a dilation effect when administered topically to the eye of the rabbit or the eye of the mouse. The concentration contains indigo. The concentration is, for example, less than about 5% (w/v), less than about 4% (w/v), less than about 3% (w/v), less than about 2% (w/v), less About 1.5% (w/v), less than about 1% (w/v), less than about 0.5% (w/v), less than about 0.2% (w/v), less than about 0.1% (w) /v), less than about 0.05% (w/v), less than about 0.01% (w/v), less than about 0.001% (w/v), or less than about 0.0001% (w/v).

When the guanidine is administered topically to the eye in the form of an eye drop, it is preferred that the eye drop contains 芜 at a concentration which substantially inhibits the elongation of the axial length when locally administered to the eye of the mouse. Ammonium. The concentration is, for example, not less than about 0.000001% (w/v), not less than about 0.00001% (w/v), not less than about 0.0001% (w/v), not less than about 0.001% (w/ v), not less than about 0.01% (w/v), not less than about 0.1% (w/v), not less than about 0.2% (w/v), not less than about 0.5% (w/v) Or no less than about 1% (w/v). More specifically, the concentration of indole ammonium should not be limited as long as it ranges from 0.000001 to about 5% (w/v), and includes, for example, preferably from about 0.00001 to about 2% (w/v), about 0.00001 to about 1% (w/v), from about 0.00001 to about 0.2% (w/v), from about 0.00001 to about 0.01% (w/v), from about 0.0001 to about 2% (w/v), from about 0.0001 About 1% (w/v), about 0.0001 to about 0.2% (w/v), about 0.0001 to about 0.01% (w/v), about 0.001 to about 2% (w/v), about 0.001 to about 1. % (w/v), from about 0.001 to about 0.2% (w/v), from about 0.001 to about 0.01% (w/v), from about 0.01 to about 2% (w/v), from about 0.01 to about 1% ( w/v), from about 0.01 to about 0.2% (w/v), from about 0.05 to about 2% (w/v), from about 0.05 to about 1% (w/v), or from about 0.05 to about 0.2% (w) More preferably from about 0.00001 to about 2% (w/v); more preferably from about 0.0001 to about 2% (w/v); most preferably from about 0.001 to about 2% (w/v); And especially from about 0.001 to about 0.2% (w/v). The above "about" means a range of error of 5%.

 [Examples]  

In the following, in order to make the present invention easy to understand the respective test results and formulation examples shown, it is not limited thereto.

Test 1. Test on inhibition of axial length elongation in myopic chick model

(Preparation of test samples)

The indole bromide was dissolved in saline to prepare 0.1 mM, 1 mM, and 3.9 mM decyl ammonium solution.

Further, atropine sulfate hydrate was dissolved in saline to prepare a 100 mM atropine solution as a reference example.

As a control group, saline solution was used.

(test method and method of administration)

A test tube having a diameter of 18 mm was cut from a height of 10 mm from the bottom, and a cut circle of the cut bottom portion was adhered to a flat rubber pad with an adhesive to prepare a lens (goggle). A 7-day-old chick (white leghorn) was obtained, and the prepared goggles were attached to the right eye of each chick with an adhesive to induce chick myopia. Its left eye is its control group.

For each of the sulphate administration groups, 20 μL of each of the prepared sulphate solutions was intravitreally administered on the day (day 0), day 2, and day 4 when the goggles were fixed. 20 μL of the atropine solution was administered to the atropine-administered group for intravitreal administration in the same manner as the procedure of the sulphate administration group, and 20 μL of the saline solution was intravitreally administered to the control group. On all days, on the 0th, 2nd, and 4th day, 20 μL of saline was administered intravitreally to the left eye of each chick.

Chicks are kept under normal feeding conditions.

(evaluation)

On the 6th day after the induction of myopia, the length of the axial length of the right and left eyeballs was measured by measuring the length of the ultrasonic eye axis ECHOSCAN US-500 (NIDEK CO., LTD.) (A-scan). The difference in the length of the axial length and the inhibition rate of the axial length elongation were calculated by the following formula.

The difference in the length of the eye axis (mm) = [the length of the eye axis of the right eye (mm)] - [the length of the eye axis of the left eye (mm)]

(test results)

The inhibition rates of the axial length elongation of the terpene ammonium administration group and the atropine administration group are shown in Table 1. ">100" in Table 1 indicates that the inhibition rate exceeds 100%.

The inhibition rate of the 100 mM atropine-administered group containing the high-concentration drug was 83%. However, the inhibition rate of the 0.1 mM sulphate administration group was 52%, although the concentration was one thousandth of the atropine concentration. Further, the inhibition rate of the 1 mM cedidomide administration group in which the concentration was one percent of the atropine concentration was 83%, which is the same inhibition rate as the inhibition rate of the 100 mM atropine administration group. In addition, the inhibition rate of the 3.9 mM sulphate administration group exceeded 100%, although the concentration was 3.9 percent of the atropine concentration.

(discussion)

As clearly shown in Table 1, it has been found that indoleamine can inhibit axial length elongation more strongly than atropine. Therefore, it is believed that indole is useful as an agent for preventing myopia, treating myopia, and/or preventing the growth of myopia, which is more powerful than atropine.

Test 2. Test for inhibition of axial length elongation in myopic mouse mode

(Preparation of test samples)

Indole bromide and glycerol were dissolved in water for injection to prepare 0.001% (w/v) and 0.05% (w/v) unadjusted pH of the ampicillin ophthalmic solution.

In a similar manner, atropine sulfate hydrate and glycerol were dissolved in water for injection to prepare a 0.1% (w/v) unregulated pH atropine ophthalmic solution.

The vehicle (control group) was isotonic water prepared by using water for injection and glycerin.

(experiment method)

Experimental myopia mouse mode:

By the 18th day after birth, the -15D hard lens was placed in the mouse (C57BL/6J) as the right eye of the experimental eye to establish a speckle lens-induced myopia mode. In short, the -15D lens is glued to the Velcro ring (with an 8 mm base curve). The matte sheet is then attached to a devil felt that has previously been affixed to the hair around the right experimental eye using cyanoacrylate. There is a 1.5 mm air gap between the back of the crystal and the anterior surface of the cornea.

Eye biometric method:

Biometric measurements of the eye such as the axial length measurement are performed using an Intra-Optical Low Coherence Interferometry (OLCI-AcMaster). The length of the eye axis was measured on the 33rd and 61st day after birth.

The ratio of inhibition of the length of the axial length of each of the examples was calculated by the following equation:

The mean value of the change in the length of the eye axis (μm) = [the length of the eye axis on the 61st day] - [the length of the eye axis on the 33rd day]

(medical treatement)

In the myopia mode induced by the spectacle lens, indigo (0.001% or 0.05%) or atropine (0.1%) is administered daily from the 33rd to the 61st day after birth. 7 μL of each drug was administered topically to the right eye daily under dark red light.

(test results)

The mean value and inhibition rate of the axial length elongation of the indole administration group and the atropine administration group are shown in Table 2.

(discussion)

As clearly shown in Table 2, it has been found that sulphate can inhibit the axial length elongation more strongly than atropine even when administered by eye drops. In addition, it has been found that guanidine can inhibit the elongation of the axial length even at low concentrations.

Trial 3. Assessment of dilated effects

(Preparation of test samples)

Indole bromide and glycerol were dissolved in water for injection to prepare 0.01% (w/v), 0.2% (w/v) and 2% (w/v) unadjusted pH guanidine ammonium ophthalmic solution.

In a similar manner, atropine sulfate hydrate and glycerol were dissolved in water for injection to prepare 0.01% (w/v) and 0.1% (w/v) unadjusted pH atropine ophthalmic solution.

(experiment method)

A single dose (5 μL) of each of the prepared ophthalmic solutions was administered to both eyes of the mice (each eye solution was 6 eyes of 6 mice). The pupil diameters of the mice were measured before administration (eyedrops) and 1, 2, 4, and 24 hours after administration. The pupil diameters of the mice measured at each measurement time point were averaged for each test sample to obtain respective average values as the respective average pupil diameters. Of each average pupil diameter at each measurement time, the longest diameter is defined as the maximum pupil diameter.

(test results)

The results are shown in Table 3.

(discussion)

Table 3 shows the maximum pupil diameter of the 0.2% aztreon ophthalmic solution group with a maximum pupil diameter of less than 0.1% atropine ophthalmic solution group. Further, Tests 1 and 2 showed that the effect of inhibiting the elongation of the axial length of the eye by sulphate was stronger than that of atropine, and even a low concentration of sulphate showed an inhibitory effect. Therefore, sulphate is used as an agent for preventing myopia growth or treating myopia, and the side effects of mydriatic action are reduced.

Formulation example

The agent of the present invention will be described in detail by reference to the formulation examples, but is not limited thereto.

Formulation Example 1: Eye Drops (0.01% (w/v))

The above eye drops can be prepared by adding indole bromide and other ingredients shown in the above table to sterile purified water, followed by thorough mixing. And by changing the amount of indole bromide added, eye drops having various concentrations, for example, an eye drop having a concentration of 0.00001-2% (w/v) can be prepared.

Formulation Example 2: Injection

The above injection can be prepared by adding the indole bromide and other components shown in the above table to the aseptic purified water, and then thoroughly mixing them to dissolve or suspend each component. Further, an injection having various concentrations, for example, an injection having from 0.01 mg to 200 mg of guanidinium bromide in 10 ml can be prepared by appropriately changing the addition amount of the indole bromide and other components shown in the above table. The injection prepared in this manner can be administered as an injection for intraocular administration, for example, an injection for intravitreal administration.

 [Industrial availability]  

Indigorin can inhibit the elongation of the axial length of the eye, and the indole is used to prevent myopia, treat myopia and/or prevent myopia growth. Further, it is desirable that indigoside is an agent for preventing myopia, treating myopia, and/or preventing the growth of myopia, characterized in that the agent has substantially no dilation effect and/or does not substantially reduce vision adjustment.

Claims (12)

 An agent for preventing myopia, treating myopia, and/or preventing the growth of myopia, comprising umeclidinium or a salt thereof as an active ingredient.    The agent of claim 1, wherein the agent has substantially no dilation effect.    The agent of claim 1 or 2, wherein the concentration of indole or a salt thereof is from about 0.000001 to about 5% (w/v).    The agent of claim 1 or 2, wherein the concentration of indole or a salt thereof is from about 0.00001 to about 2% (w/v).    The agent of claim 1 or 2, wherein the concentration of indole or a salt thereof is from about 0.0001 to about 2% (w/v).    The agent of claim 1 or 2, wherein the concentration of indole or a salt thereof is from about 0.001 to about 2% (w/v).    The agent of claim 1 or 2, wherein the concentration of indole or a salt thereof is from about 0.001 to about 0.2% (w/v).    The agent according to any one of claims 1 to 7, which is for topical administration to the eye.    The agent of claim 8, wherein the topical administration of the eye is instillation administration or intravitreal administration.    The agent according to any one of claims 1 to 9, which is formulated in the form of an eye drop, an ophthalmic gel, an ophthalmic ointment or an injection.    The agent according to any one of claims 1 to 10, wherein the indole or its salt is umeclidinium bromide.    An agent for inhibiting the elongation of an axial length comprising indole or a salt thereof as an active ingredient.