WO2018174145A1

WO2018174145A1 - Agent for preventing myopia, treating myopia, and/or preventing myopia progression comprising umeclidinium as active ingredient

Info

Publication number: WO2018174145A1
Application number: PCT/JP2018/011354
Authority: WO
Inventors: Donald Tan; Roger Beuerman; Seang-Mei SAW; Aradhana UPADHYAY; Masatomo Kato; Takaaki Inaba
Original assignee: Singapore Health Services Pte Ltd; Santen Pharmaceutical Co., Ltd.
Priority date: 2017-03-23
Filing date: 2018-03-22
Publication date: 2018-09-27
Also published as: TW201838629A

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

AGENT FOR PREVENTING MYOPIA, TREATING MYOPIA, AND/OR PREVENTING MYOPIA PROGRESSION COMPRISING UMECLIDINIUM AS ACTIVE INGREDIENT

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

Myopia is a form of ametropia, which is a pathology that the eyesight blurs because the light from a long distance which enters eyes makes an image before retina. In case that the refractive power of cornea/lens is too strong, when a person looks into the far distance, the image is not focused on retina, but focused before retina. Such myopia is referred to as refractive myopia. On the other hand, in case that the axial length which is the length between cornea and retina is extended, i.e., too longer than normal, when a person looks into the far distance, the image is not focused on retina, but focused before retina, even though the thickness of lens is reduced. Such myopia is referred to as axial myopia. The development of myopia at an early age or fast progression of myopia may lead to high myopia as an adult with associated visually disabling pathologic myopia lesions. In order to prevent myopia, treat myopia, and/or prevent myopia progression, various studies based on surgery, optical wear or medication have been tried.

Atropine is known as its sulfate hydrate form shown below, which has a preventing action on myopia progression by reducing axial elongation (Patent Literature 1). However, atropine has a significant dose-related mydriatic action, which may result in unacceptable glare and photophobia, a loss of depth of focus, and potentially allowing more UV light entry into the eye. Atropine also reduces normal accommodation in a dose dependent manner, which can result in poor near vision. These side-effects reduce the clinical effectiveness of using high concentrations of atropine in the clinical setting, although low dose atropine has been shown to still be effective in reducing axial elongation, but with less mydriasis and accommodation loss.

In the meantime, umeclidinium, in particular, umeclidinium bromide (hereinafter, "umeclidinium bromide" may be also referred to as just "umeclidinium"), is a compound represented by the following chemical formula, which has been on sale as an inhalant powder (ENCRUSE^TM) which can relieve various symptoms based on obstructive airway disorder in chronic obstructive pulmonary disease (COPD).

Patent Literature 2 discloses a pharmaceutical combination product comprising umeclidinium bromide and corticosteroid for treating COPD and asthma. However, there has not been reported about the effect of umeclidinium through the ocular topical administration, in particular, about its effect preventing myopia, treating myopia, and/or preventing myopia progression.

[Patent Literature 1] WO 2012/161655
[Patent Literature 2] WO 2012/168161

The purpose of the present invention may be to find a novel compound useful for preventing myopia, treating myopia, and/or preventing myopia progression. In addition, the purpose of the present invention may be to find a novel compound useful for preventing myopia, treating myopia, and/or preventing myopia progression with reduced side-effects due to mydriatic action.

The present inventors have intensively studied to solve the aforementioned problem and have discovered that umeclidinium which is used in the treatment of chronic obstructive pulmonary disease (COPD) can suppress the axial length elongation, and umeclidinium is therefore useful for preventing myopia, treating myopia, and/or preventing myopia progression. In addition, the present inventors have also found that umeclidinium has the effect suppressing the axial length elongation even in much lower dose than atropine, and further has a lower mydriatic action which is a side-effect than atropine. Based upon the new findings, the present invention has been completed.

The present invention may relates to the followings.
(Term 1) An agent for preventing myopia, treating myopia, and/or preventing myopia progression, comprising umeclidinium or a salt thereof as an active ingredient.

(Term 2) The agent of Term 1, characterized in that the agent does not substantially have mydriatic action.

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

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

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

(Term 6) The agent of Term 1 or 2, wherein the concentration of umeclidinium or a salt thereof is about 0.001 to about 2 % (w/v).

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

(Term 8) The agent of any one of Terms 1 to 7, which is for ocular topical administration.

(Term 9) The agent of Term 8, wherein the ocular topical administration is instillation administration or intravitreal administration.

(Term 10) The agent of any one of Terms 1 to 9, whose formulation type is eyedrop, eye gel, ophthalmic ointment or injection.

(Term 11) The agent of any one of Terms 1 to 10, wherein umeclidinium or a salt thereof is umeclidinium bromide.

(Term 12) An agent for suppressing the axial length elongation, comprising umeclidinium or a salt thereof as an active ingredient.

(Term 13) Use of umeclidinium or a salt thereof in the manufacture of an agent for preventing myopia, treating myopia, and/or preventing myopia progression.

(Term 14) Umeclidinium or a salt thereof for use in preventing myopia, treating myopia, and/or preventing myopia progression.

(Term 15) A pharmaceutical composition comprising umeclidinium or a salt thereof for use in preventing myopia, treating myopia, and/or preventing myopia progression.

(Term 16) A method for preventing myopia, treating myopia, and/or preventing myopia progression, comprising administering a therapeutically effective amount of umeclidinium or a salt thereof to a mammal in need thereof.

Effect of Invention

As shown in the experimental results mentioned below, it was demonstrated that umeclidinium can suppress the axial length elongation more potently than atropine. Thus, umeclidinium is thought to be useful as a more potent agent for preventing myopia, treating myopia, and/or preventing myopia progression than atropine. In addition, it was also demonstrated that umeclidinium has the effect suppressing the axial length elongation even in much lower dose than atropine, and further has a lower mydriatic action which is a side-effect than atropine, and hence umeclidinium is expected to become a practical agent for preventing myopia, treating myopia, and/or preventing myopia progression with reduced side-effects disturbing daily life due to mydriatic action and/or accommodative loss.

Some embodiments of the present invention are explained in detail below.

The "agent for preventing myopia, treating myopia, and/or preventing myopia progression" used herein comprises umeclidinium or a salt thereof as an active ingredient.

The "salt of umeclidinium" used herein is not limited as long as it is a salt with a pharmaceutically acceptable anion. For example, the salt includes a salt with hydroxide ion; a salt with an inorganic acid anion such as nitrate, sulfate and phosphate; a salt with an organic acid anion such as acetate, fumarate, maleate, succinate, citrate, tartrate, adipate, gluconate, glucoheptonate, glucuronate, terephthalate, methanesulfonate, lactate, hippurate, 1,2-ethanedisulfonate, isethionate, lactobionate, oleinate, pamoate, polygalacturonate, stearate, tannate, trifluoromethanesulfonate, benzenesulfonate, p-toluenesulfonate, laurylsulfate, methyl sulfate, naphthalenesulfonate, and sulfosalicylate; and a salt with a halogen ion such as bromine ion, fluorine ion, chlorine ion, and iodine ion. In the present invention, the particularly preferred salt of umeclidinium is the salt with bromine ion.

The chemical name of "umeclidinium bromide" is 1-[2-(benzyloxy)ethyl]-4-(hydroxydiphenylmethyl)-1-azoniabicyclo[2.2.2]octane bromide, whose chemical structure is shown below.

And, the "umeclidinium or a salt thereof" may be in a hydrate form or in a solvate form.

When "umeclidinium or a salt thereof" is a geometric isomer or an optical isomer, the present invention encompasses these isomers. And, when "umeclidinium or a salt thereof" has a proton tautomer, the present invention also encompasses such tautomer or a salt thereof.

When "umeclidinium or a salt thereof" has a polymorphism and a polymorphism group (polymorphism system), the present invention also encompasses these polymorphism and polymorphism group (polymorphism system). The polymorphism group (polymorphism system) used herein means a crystal form at the respective stages and the entire course when the crystal form is changed with the conditions and states of preparation, crystallization, preservation, etc.

The "umeclidinium or a salt thereof" can be prepared in a general manner or can be also obtained as a commercially available product. For example, umeclidinium bromide is commercially offered by MedChem express (product code: HY-12100).

The concentration of "umeclidinium or a salt thereof" used herein is not particularly limited, but 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 - 1 % (w/v), more preferably 0.0001 - 0.2 % (w/v), and 0.001 to 0.2 % (w/v), even more preferably 0.0001 - 0.1 % (w/v), particularly preferably 0.0001 - 0.01 % (w/v), in case of eyedrops.
The concentration of "umeclidinium or a salt thereof" used herein may mean a concentration of free form of umeclidinium, or a concentration of a salt thereof.

The term "not substantially have mydriatic action" in the present invention means that the agent has no mydriatic action of the level to disturb daily life. Hence, 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 disturbs his/her daily life.

The "myopia" in the present invention is defined as a refractive state of an uncorrected eye where light rays meet the eye before the retina. The "myopia" in the present invention includes all and every known classification and definition of myopia including axial myopia, refractive myopia, pathological myopia, simple myopia, extreme myopia, severe myopia, strong myopia, moderate myopia, and light myopia.

The "agent for preventing myopia, treating myopia, and/or preventing myopia progression" used herein includes an agent for preventing refractive myopia, treating refractive myopia, and/or preventing refractive myopia progression and an agent for preventing axial myopia, treating axial myopia, and/or preventing axial myopia progression, preferably an agent for preventing axial myopia, treating axial myopia, and/or preventing axial myopia progression. The term "preventing myopia progression" used herein may mean slowing myopia progression or reducing myopia progression. The term "preventing myopia" used herein may mean preventing the onset of myopia or delaying the onset of myopia.
As shown in the experimental results mentioned below, umeclidinium can suppress the axial length elongation, and hence the present invention may also include an agent for suppressing the axial length elongation, comprising umeclidinium or a salt thereof as an active ingredient.

The "umeclidinium or a salt thereof" in the present invention is preferably used for preventing myopia, treating myopia and/or preventing myopia progression, in particular more preferably, for preventing myopia in schoolage children or in teenagers or adults with myopia progression and/or for preventing myopia progression in schoolage children or in teenagers or adults with myopia progression.

The usage of the "agent for preventing myopia, treating myopia, and/or preventing myopia progression" in the present invention can vary depending on dosage form; symptom severity; age, age of onset of myopia, parental myopia, body weight of patient in need thereof; physician's discretion; etc. As for eyedrops, the agent can be administered in eyedrops, for example, every day to every one week, preferably every day, in an amount of 1 - 5 drops each time, preferably 1 - 3 drops each time, more preferably 1 - 2 drops each time, even more preferably 1 drop each time, at a frequency of 1 - 4 times a day, preferably 1 - 3 times a day, more preferably once or twice a day, particularly preferably once a day. Preferably, it is administered in eyedrops every day, with 1 drop once a day.

In the present invention, umeclidinium can be administered topically, orally, or parenterally, and the administration style thereof includes an ocular topical administration including sustained continuous delivery to the eye (instillation administration, administration of an ophthalmic ointment, conjunctival sac administration, intravitreal administration, subconjunctival administration, Tenon capsule administration, etc.), an oral administration, an intravenous administration, and a transdermal administration.

Preferred formulations for topically-administering umeclidinium to eyes include an eyedrop, an eye gel and an ophthalmic ointment, and also an injection thereof can be used for this administration, particularly an injection for subconjunctival administration, Tenon capsule administration or intravitreal administration. The present formulation comprising umeclidinium as an active ingredient can be prepared with optionally-necessary pharmaceutically-acceptable additives by forming it to a dosage form suitable for a desired administration.

In the present invention, a dosage form suitable for oral administration includes, for example, a tablet, a capsule, a granule, and a powder, and a dosage form suitable for parenteral administration includes, for example, an injection, an eyedrop, an eye gel, an ophthalmic ointment, a patch, a gel, and an intercalating agent. These dosage forms can be prepared in a general manner used widely in the art.

In order to sustain the therapeutic effect of the present invention further effectively, a DDS formulation such as a formulation for intraocular implant and a microsphere can be used.

The eyedrop can be prepared with some optional additives selected from, for example, a tonicity agent, a buffer agent, a surfactant, a stabilizing agent, a preservative, or the like, as needed. The pH of the eyedrop is not limited as long as the pH is in an acceptable range for ophthalmic formulations, generally a range of 2 - 8 is preferable. The tonicity agent includes, for example, sodium chloride. The buffer agent includes, for example, sodium phosphate and sodium acetate. The surfactant includes, for example, polyoxyethylene sorbitan monooleate, polyoxyl 40 stearate, and polyoxyethylene hydrogenated castor oil. The stabilizing agent includes, for example, sodium citrate, and disodium edetate. The preservative includes, for example, benzalkonium chloride and paraben.

When the formulation of the present invention comprising umeclidinium as an active ingredient is an eyedrop, an eye gel or an ophthalmic ointment, the formulation may comprise a preservative agent or may not.

The ophthalmic ointment can be prepared with a widely-used base material such as white petrolatum and liquid paraffin.

The tablet can be prepared with some optional additives selected from, for example, an excipient, a disintegrant, a binder, a lubricant, a coating agent, a flavor, or the like, as needed. The excipient includes, for example, lactose, glucose, D-mannitol, anhydrous dibasic calcium phosphate, starch, and sucrose. The disintegrant includes, for example, carboxymethylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, crospovidone, starch, partially-pregelatinized starch, and low substituted hydroxypropylcellulose. The binder includes, for example, hydroxypropylcellulose, ethylcellulose, gum arabic, starch, partially-pregelatinized starch, polyvinylpyrrolidone, and polyvinyl alcohol. The lubricant includes, for example, magnesium stearate, calcium stearate, talc, hydrated silicon dioxide, and hydrogenated oil. The coating agent includes, for example, purified sucrose, hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, and polyvinylpyrrolidone. The flavor includes, for example, citric acid, aspartame, ascorbic acid, and menthol.

The injection can be prepared with some optional additives selected from, for example, a tonicity agent, a buffer agent, a surfactant, a thickener, or the like, as needed. The tonicity agent includes, for example, sodium chloride. The buffer agent includes, for example, sodium phosphate. The surfactant includes, for example, polyoxyethylene sorbitan monooleate. The thickener includes, for example, methylcellulose.

For example, the intercalating agent can be prepared by mixing and milling umeclidinium and a biodegradable polymer such as hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxy vinyl polymer, and polyacrylic acid, and then compacting the obtained powder. As appropriate, an excipient, a binder, a stabilizing agent, and/or a pH adjuster may be used therein.

For example, the formulation for intraocular implant can be prepared with a biodegradable polymer such as polylactide, polyglycolate, lactide-glycolate copolymer, and hydroxypropylcellulose.

When umeclidinium is topically administered to the eyes in the form of an eyedrop, it is preferred that the eyedrop contains umeclidinium at such a concentration that the mydriatic action is not substantially caused when topically administered to the rabbit’s eyes or mouse’s eyes. 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 than 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 umeclidinium is topically administered to the eyes in the form of an eyedrop, it is preferred that the eyedrop contains umeclidinium at such a concentration that the axial length elongation is substantially suppressed when topically administered to the mouse’s eyes. 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 not less than about 1 % (w/v). In more detail, the concentration of umeclidinium should not be limited as long as the range thereof is in 0．000001 - about 5 % (w/v), which includes, for example, preferably about 0.00001 - about 2 % (w/v), about 0.00001 - about 1 % (w/v), about 0.00001 - about 0.2 % (w/v), about 0.00001 - about 0.01 % (w/v), about 0.0001 - about 2 % (w/v), about 0.0001 - about 1 % (w/v), about 0.0001 - about 0.2 % (w/v), about 0.0001 - about 0.01 % (w/v), about 0.001 - about 2 % (w/v), about 0.001 - about 1 % (w/v), about 0.001 - about 0.2 % (w/v), about 0.001 - about 0.01 % (w/v), about 0.01 - about 2 % (w/v), about 0.01 - about 1 % (w/v), about 0.01 - about 0.2 % (w/v), about 0.05 - about 2 % (w/v), about 0.05 - about 1 % (w/v), or about 0.05 - about 0.2 % (w/v); more preferably about 0.00001 - about 2 % (w/v); much more preferably about 0.0001 - about 2 % (w/v); the most preferably about 0.001 - about 2 % (w/v); and particularly about 0.001 - about 0.2 % (w/v). The "about" mentioned above means error range of 5 %.

Here is each test result and formulation examples, which are shown in order to make it easy to understand the present invention, but should not be limited thereto.

Test 1. Test about suppression of axial length elongation in myopia chick model
(Preparation of test sample)
Umeclidinium bromide was dissolved in saline to prepare 0.1 mM, 1 mM and 3.9 mM umeclidinium solutions.
And, atropine sulfate hydrate was dissolved in saline to prepare 100 mM atropine solution as a reference example.
As a control, saline was used.

(Test method and administration method)
A test tube having a diameter of 18 mm was cut off at the level of 10 mm from the bottom, and the cutting circle of the cut-off bottom part was bonded to a flat rubber packing with an adhesive agent to prepare a lens (goggle). 7-day-old chicks (white leghorns) were obtained, and the prepared goggle was attached to the right eye of each chick with an adhesive agent to induce myopia to the chicks. The left eye thereof was its control.
To each of the umeclidinium administration groups, 20 μL of each prepared umeclidinium solution was intravitreally administered on the day that the goggle was fixed (on day 0), on day 2, and on day 4. In the same way as the procedure in the umeclidinium administration groups, 20 μL of the atropine solution was intravitreally administered to the atropine administration group, and 20 μL of saline was intravitreally administered to the control group. In the all groups, 20 μL of saline was intravitreally administered to the left eye of each chick, on day 0, day 2, and day 4.
The chicks were reared under a normal rearing condition.

(Evaluation)
On day 6 from the myopia induction, the axial length of right and left eyeballs was measured with a ultrasound axial length measurement ECHOSCAN US-500 (NIDEK CO.,LTD.) (A-scan). The difference of axial lengths and the suppression rate of the axial length elongation were calculated by the following formulae.
Difference of axial lengths (mm) =
[axial length (mm) of right eye] - [axial length (mm) of left eye]
Suppression rate of axial length elongation (%) =

(Test result)
The suppression rates of the axial length elongation in the umeclidinium administration group and the atropine administration group are shown in Table 1. The ">100" in Table 1 denotes that the suppression rate is over 100 %.

The suppression rate in 100 mM atropine administration group including the high concentration drug was 83 %. Whereas, the suppression rate in 0.1 mM umeclidinium administration group was 52 %, though the concentration thereof is one thousandth of the atropine's concentration. And, the suppression rate in 1 mM umeclidinium administration group in which the concentration thereof is one hundredth of the atropine's concentration was 83 %, which was the same suppression rate as that of 100 mM atropine administration group. In addition, the suppression rate in 3.9 mM umeclidinium administration group was over 100 %, though the concentration thereof is 3.9 hundredth of the atropine's concentration.

(Discussion)
As clearly exhibited in Table 1, it has been found that umeclidinium can suppress the axial length elongation more potently than atropine. Thus, it is thought that umeclidinium is useful as a more potent agent for preventing myopia, treating myopia, and/or preventing myopia progression than atropine.

Test 2. Test about suppression of axial length elongation in myopia mice model
(Preparation of test sample)
Umeclidinium bromide and glycerin were dissolved in water for injection to prepare 0.001 % (w/v) and 0.05 % (w/v) umeclidinium ophthalmic solutions without adjusting pH.
In a similar way, atropine sulfate hydrate and glycerin were dissolved in water for injection to prepare 0.1 % (w/v) atropine ophthalmic solution without adjusting pH.
The vehicle (control) was isotonic water which was prepared with water for injection and glycerin.

(Test method)
Murine model of experimental myopia:
Spectacle lens-induced myopia model was established by placing -15D hard lens on the right eye of mice (C57BL/6J), which was served as the experimental eye, at post-natal days 18. Briefly, a -15D lens was glued to an annulus (with 8 mm base curve) of Velcro. This mating piece was then attached to the Velcro that had been previously glued to the hair around the right experimental eye using a cyanoacrylate. An air gap of 1.5 mm existed between the back part of the lens and the anterior surface of the cornea.

Ocular biometry methods:
Ocular biometry such as axial length measurement was done using in vivo Optical Low Coherence Interferometry (OLCI-AcMaster). The axial length was measured at post-natal days 33 and 61.

The ratio for suppressing the axial length elongation with each example was calculated by the following equation:
Mean values for the changes in the axial length (μm) = [axial length on day 61] - [axial length on day 33]
Suppression rate (%)of axial length elongation =

(Drug Treatment)
Umeclidinium (at 0.001 % or 0.05 %) or atropine (at 0.1 %) was administered once a day post-natal day 33 until day 61 in the spectacle lens-induced myopia model. 7μL of each drug was administered topically to the right eye in dim red light at the each day.

(Test result)
The mean values and suppression rates of the axial length elongation in the umeclidinium administration group and the atropine administration group are shown in Table 2.

(Discussion)
As clearly exhibited in Table 2, it has been found that umeclidinium can suppress the axial length elongation more potently than atropine, even by eyedrop administration. Furthermore, it has been found that umeclidinium can suppress the axial length elongation even in low concentration.

Test 3. Evaluation of mydriatic action
(Preparation of test sample)
Umeclidinium bromide and glycerin were dissolved in water for injection to prepare 0.01 % (w/v), 0.2 % (w/v), and 2 % (w/v) umeclidinium ophthalmic solutions without adjusting pH.
In a similar way, atropine sulfate hydrate and glycerin were dissolved in water for injection to prepare 0.01 % (w/v), and 0.1 % (w/v) atropine ophthalmic solutions without adjusting pH.

(Test method)
A single dose (5 μL) of each prepared ophthalmic solution was administered to both eyes of mice (6 eyes of 3 mice per each ophthalmic solution). Before the administration (eyedrop), and 1, 2, 4 and 24 hours after the administration, each pupil diameter of the mice was measured. The measured pupil diameters of the mice at each measurement time per each test sample were averaged to obtain each average value as each average pupil diameter. Among each average pupil diameter at each measurement time, the longest diameter was defined as the maximum pupil diameter.

(Test result)
The results are shown in Table 3.

(Discussion)
Table 3 showed that the maximum pupil diameter of 0.2 % umeclidinium ophthalmic solution group was smaller than that of 0.1 % atropine ophthalmic solution group. In addition, Tests 1 and 2 showed that the effect suppressing the axial length elongation with umeclidinium is more potent than that of atropine, and even a low concentration of umeclidinium exhibits the suppression effect. Thus, umeclidinium is useful as an agent for preventing myopia progression or treating myopia, whose side-effect of mydriatic action is reduced.

Formulation example
The agents of the present invention are explained in detail by referring formulation examples, but should not be limited only thereto.

Formulation example 1: eyedrop (0.01 % (w/v))

The above eyedrop can be prepared by adding umeclidinium bromide and the other ingredients shown in the above table to sterile purified water and then sufficiently mixing it. And, by changing the additive amount of umeclidinium bromide, it is possible to prepare eyedrops having various concentrations, for example, an eyedrop having a concentration of 0.00001 - 2 % (w/v).

Formulation example 2: injection

The above injection can be prepared by adding umeclidinium bromide and the other ingredients shown in the above table to sterile purified water and then sufficiently mixing it to dissolve or suspend each ingredient. And, by suitably changing the additive amounts of umeclidinium bromide and the other ingredients shown in the above table, it is possible to prepare injections having various concentrations, for example, an injection having 0.01 mg - 200 mg of umeclidinium bromide in 10 ml thereof. The injection prepared in this way can be administered as an injection for intraocular administration such as an injection for intravitreal administration.

Umeclidinium can suppress the axial length elongation, and umeclidinium is useful for preventing myopia, treating myopia, and/or preventing myopia progression. And, umeclidinium is expected as an agent for preventing myopia, treating myopia, and/or preventing myopia progression, which is characterized in that the agent does not substantially have mydriatic action and/or reduce accommodation.

Claims

An agent for preventing myopia, treating myopia, and/or preventing myopia progression, comprising umeclidinium or a salt thereof as an active ingredient.
The agent of claim 1, characterized in that the agent does not substantially have mydriatic action.
The agent of claim 1 or 2, wherein the concentration of umeclidinium or a salt thereof is about 0.000001 to about 5 % (w/v).
The agent of claim 1 or 2, wherein the concentration of umeclidinium or a salt thereof is about 0.00001 to about 2 % (w/v).
The agent of claim 1 or 2, wherein the concentration of umeclidinium or a salt thereof is about 0.0001 to about 2 % (w/v).
The agent of claim 1 or 2, wherein the concentration of umeclidinium or a salt thereof is about 0.001 to about 2 % (w/v).
The agent of claim 1 or 2, wherein the concentration of umeclidinium or a salt thereof is about 0.001 to about 0.2 % (w/v).
The agent of any one of claims 1 to 7, which is for ocular topical administration.
The agent of claim 8, wherein the ocular topical administration is instillation administration or intravitreal administration.
The agent of any one of claims 1 to 9, whose formulation type is eyedrop, eye gel, ophthalmic ointment or injection.
The agent of any one of claims 1 to 10, wherein umeclidinium or a salt thereof is umeclidinium bromide.
An agent for suppressing the axial length elongation, comprising umeclidinium or a salt thereof as an active ingredient.