Eye drops for inhibiting myopia progression comprising alpha1 blocker

Abstract

The present invention addresses the problem of providing a novel eye drop for suppressing the progression of myopia, the eye drop being capable of suppressing the progression of myopia only by being easily dropped into the eye. The problem is solved by an eye drop for suppressing the progression of myopia, which contains an [alpha] 1 blocker. It is preferable that the [alpha] 1 blocker is contained in the range of more than 0.001 mg / mL and 1.4 mg / mL or less in terms of [alpha] 1 blocker salt. The alpha1 blocker is one or more substances selected from the group consisting of Bronzosin, Prazosin, Urapidil, Moxicetiril, and Ketexikine.

Description

Technical Field

[0001] The present invention relates to an eye drop for inhibiting myopia progression, comprising an α1 blocker. Background Art

[0002] Myopia is particularly common among Asians, especially Japanese, and the proportion of deep myopia above -5D is also high. In addition, myopia has been increasing worldwide in recent years, and in Japan, the proportion of children with naked eye visual acuity below 1.0 has increased year by year. In addition, it is known that myopia progresses rapidly during the school age of 7 to 12 years old (refer to non-patent literature 1).

[0003] Myopia is classified into refractive myopia, accommodative myopia (pseudomyopia) and axial myopia according to its pathogenesis, and the myopia progression of school age is mainly axial myopia. Human eyes are hyperopic just after birth, and the degree of hyperopia decreases due to the extension of the eye axis during the growth period, and then normalizes when entering school age. The eye axis extension after this normalization phenomenon directly leads to myopia, and the eye axis length cannot be restored once it is extended. Therefore, it is believed that suppressing the extension of the eye axis during the growth period to the school age is effective for the prevention or treatment of myopia (refer to non-patent literature 2). In addition, not only during the growth period, the eye axis of adults will also extend, and it is said that the eye axis extension of adults is a risk factor for various eye diseases.

[0004] Therapeutic agents for preventing myopia have been proposed, for example, Rho kinase inhibitors (see Patent Document 1), bradykinin (Patent Document 2), crocetin (Patent Document 3), etc. In addition, the present inventors have proposed an eye drop for suppressing myopia containing bunazosin (Patent Document 4).

[0005] Prior art literature

[0006] Non-patent literature

[0007] Non-patent document 1: Medical Science, Vol.253, No.2, 2015

[0008] Non-patent literature 2: Ophthalmology, Vol. 58, No. 6, 635-641, 2016

[0009] Patent Literature

[0010] Patent Document 1: WO2010 / 010702

[0011] Patent Document 2: Japanese Patent Application Publication No. 2011-144111

[0012] Patent Document 3: WO2018 / 212152

[0013] Patent Document 4: Japanese Patent No. 6917103 Summary of the invention

[0014] Problem that the invention aims to solve

[0015] The object of the present invention is to provide a novel eye drop for inhibiting the progression of myopia, which can inhibit the progression of myopia by simple means.

[0016] Solutions for solving problems

[0017] The eye drops for inhibiting myopia progression of the present invention are characterized by comprising an α1 blocker. The α1 blocker is preferably contained in a range of more than 0.001 mg / mL and less than 1.4 mg / mL in terms of α1 blocker salt. The α1 blocker is one or more selected from the group consisting of bunazosin, prazosin, urapidil, moxisylyte and corynanthine.

[0018] Effects of the Invention

[0019] According to the present invention, the myopic person can inhibit the progression of myopia by simply applying eye drops, instead of having a doctor perform injections in a medical institution. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The figure is a photo of mice used in myopia induction experiments (right eye wearing -30D lens, left eye wearing 0D).

[0021] Figure 2 The results of (Experiment 1) are as follows: the refractive power when eye drops containing bunazosin, prazosin and urapidil as α1 blockers were instilled into myopic eyes and non-myopic eyes.

[0022] Figure 3 The results of (Experiment 1) are as follows: the axial length of the eye when eye drops containing bunazosin, prazosin and urapidil as α1 blockers were instilled into myopic eyes and non-myopic eyes.

[0023] Figure 4 The results of (Experiment 2) are the refractive power results when eye drops with different α1 blocker contents were instilled into myopic eyes and non-myopic eyes.

[0024] Figure 5 The results of (Experiment 2) are as follows: the axial length of the eye when eye drops with different contents of α1 blockers were instilled into myopic eyes and non-myopic eyes. DETAILED DESCRIPTION

[0025] The eye drops for inhibiting myopia progression containing an α1 blocker of the present invention are described below. The present invention is not limited to the contents of the following embodiments and examples, and includes various modifications and application examples within the scope of the gist of the present invention.

[0026] Regarding the present invention, the inventors have conducted continuous research on inhibiting the progression of myopia, and provide an eye drop containing an α1 blocker that can inhibit the progression of myopia by a simple means of dropping the drops into the eyes of the myopic person themselves, rather than being directly injected into the eyes of the myopic person by a physician in a medical institution. In the present application, as shown in the experimental examples described later, the liquid eye drops containing an α1 blocker are dropped into a mouse myopia model and the refractive index and axial length of the eye are evaluated to verify the effect of inhibiting the progression of myopia.

[0027] Eye drops are liquid eye drops (also called eye drops) that are usually provided in the form of eye drop containers. Such eye drops can be easily dropped into the eyes by the myopic person himself. Examples of α1 blockers contained in eye drops include: Bunazosin, Prazosin, Urapidil, Moxisylyte, Corynanthine, etc., and one or more of these may be included.

[0028] The content of the α1 blocker is preferably in the range of more than 0.001 mg / mL and less than 1.4 mg / mL. It should be noted that, as shown in Experiment 2 described later, it is particularly preferred to be 0.01 mg / mL or more in terms of the α1 blocker salt. The usage and dosage of eye drops vary depending on the patient's symptoms, age, etc., but generally, eye drops can be applied about 1 to 6 times per day, with about 1 to 2 drops per time. It should be noted that there is no particular limitation on the upper limit of the content, but in this specification, a more realistic upper limit concentration can be set according to the solubility of the α1 blocker salt used. For example, regarding the solubility in water, bunazosin hydrochloride is 7.7 to 9.1 mg / mL, prazosin hydrochloride is 1.4 mg / mL, urapidil hydrochloride is 25 mg / mL, and doxazosin hydrochloride is about 5 mg / mL. Considering these, 1.4 mg / mL is set as the upper limit of the α1 blocker salt.

[0029] As other ingredients that can be included in the eye drops, there can be listed: pharmacologically active ingredients, physiologically active ingredients, glaucoma eye drops ingredients, etc. These ingredients can be included within the scope that does not damage the effect of the present invention. Within the scope that does not damage the effect of the present invention, the eye drops can also arbitrarily contain one or more of the other various ingredients and additives according to the conventional method according to its use and form as needed. As these ingredients and additives, for example, various additives such as spices or cooling agents, preservatives, bactericides or antibacterial agents, pH adjusters, chelating agents, stabilizers, isotonic agents, buffers, etc. can be listed. By making the known eye drops contain α1 blockers, the effect of inhibiting the progression of myopia can be further improved.

[0030] As described above, the present invention is an eye drop for inhibiting myopia progression containing an α1 blocker, but the present invention can also be represented by the following other invention categories: (i) use of a composition containing an α1 blocker as an eye drop for inhibiting myopia progression; (ii) use of a composition containing an α1 blocker in the manufacture of an eye drop for inhibiting myopia progression; (iii) a method for inhibiting myopia progression by administering a composition containing an α1 blocker as an eye drop for inhibiting progression; etc. It should be noted that the so-called "effect of inhibiting myopia progression" in this specification refers to the effect of inhibiting the progression of axial myopia.

[0031] Example

[0032] The present invention is further described in detail by the following experiments.

[0033] [Measurement]

[0034] like Figure 1 As shown, mice (C57BL6 / J, CLEA Co., Ltd., Japan) aged 3 weeks after birth were given 0D ("D" refers to the abbreviation of diopter, which is the unit of diopter of lenses) in the left eye and -30D lenses in the right eye to induce myopia for 3 weeks. During the myopia induction period, eye drops were given once a day. Phosphate buffered saline (PBS) was used as a control group (Control), and α1 blocker was used as a test group. As α1 blockers, bunazosin, prazosin, and urapidil were used.

[0035] After 3 weeks, the refractive index and axial length of the mouse eyeball were measured, and the changes were calculated. An infrared photorefractor for mice (made by Professor Schaeffel of the University of Tubingen) was used to measure the refractive index. The closer the refractive index is to a negative number, the deeper the myopia. Axial length was measured using spectral-domain optical coherence tomography (Envisu R4310, made by Leica). The larger the value of the axial length, the deeper the myopia.

[0036] [Experiment 1]

[0037] (Experimental Method)

[0038] PBS (control group), bunazosin eye drops (0.1 mg / mL bunazosin hydrochloride), prazosin eye drops (0.1 mg / mL prazosin hydrochloride), and urapidil eye drops (0.1 mg / mL urapidil hydrochloride) were used as eye drops. They were instilled once a day for 3 weeks during the myopia induction period.

[0039] (Experimental results)

[0040] Figure 2 The result is the refractive index. In the control group (PBS), the eyes wearing -30D lenses (-14.05±3.71) had a deeper degree of myopia than the eyes wearing 0D lenses (2.55±2.74). On the other hand, in the α1 blocker eye drop group, regardless of whether it was bunazosin, prazosin, or urapidil, the difference between the eyes wearing -30D lenses (-0.74±4.07, -2.03±5.33, and -5.51±6.29, respectively) and the eyes wearing 0D lenses (3.65±4.72, 3.97±2.34, and 0.33±7.07, respectively) was small, and the progression of myopia was suppressed.

[0041] Figure 3 The results are for axial length. In the control group (PBS), the axial length of eyes wearing -30D lenses (0.227±0.015) was longer than that of eyes wearing 0D lenses (0.190±0.014). On the other hand, in the α1 blocker eye drop group, regardless of whether it was bunazosin, prazosin, or urapidil, the difference in axial length between eyes wearing -30D lenses (0.191±0.026, 0.200±0.018, 0.233±0.020, respectively) and eyes wearing 0D lenses (0.187±0.019, 0.190±0.014, 0.217±0.014, respectively) was small, and the progression of myopia was suppressed.

[0042] From the above results, it can be seen that the eye drops containing α1 blockers show the effect of inhibiting the progression of myopia.

[0043] [Experiment 2]

[0044] (Experimental Method)

[0045] The concentration of α1 blocker eye drops (mg of α1 blocker salt contained in 1 mL: mg / mL) was set to 0.001 (mg / mL), 0.01 (mg / mL), and 0.1 (mg / mL) as eye drops. Each eye drop was instilled once a day for 3 weeks during the myopia induction period. The control group was PBS eye drops containing no α1 blocker, and the α1 blocker eye drops were eye drops containing a predetermined concentration of bunazosin hydrochloride.

[0046] (Experimental results)

[0047] Figure 4 The result is the refractive index. In the PBS (control group) (α1 blocker concentration: 0 mg / mL), the eyes wearing -30D lenses (-13.59±3.35) had deeper myopia than the eyes wearing 0D lenses (2.06±2.02). In the eye drop group with an α1 blocker concentration of 0.001 (mg / mL), the eyes wearing -30D lenses (-10.90±4.13) had deeper myopia than the eyes wearing 0D lenses (-0.33±3.47). Although the effect of inhibiting myopia progression was observed to be slightly inhibited compared to the PBS (control group) (α1 blocker concentration: 0 mg / mL), the effect of inhibiting myopia progression was not fully obtained compared to when the α1 blocker concentration was 0.01 (mg / mL) or above. Therefore, it is easy to infer that even if the α1 blocker concentration of 0.001 (mg / mL) is insufficient, the effect of inhibiting the progression of myopia can be observed when the α1 blocker concentration exceeds 0.001 (mg / mL). On the other hand, in the eye drop groups with α1 blocker concentrations of 0.01 (mg / mL) and α1 blocker concentrations of 0.1 (mg / mL), the difference between the eyes wearing -30D lenses (-6.92±4.08, -1.26±3.28, respectively) and the eyes wearing 0D lenses (-0.83±3.20, 3.19±3.76, respectively) was small, and the progression of myopia was inhibited.

[0048] Figure 5 The results are for axial length. In the PBS (control group) (α1 blocker concentration: 0 mg / mL), the axial length of the eyes wearing -30D lenses (0.226±0.017) was longer than that of the eyes wearing 0D lenses (0.194±0.015). In the eye drop group with α1 blocker concentration of 0.001 (mg / mL), the axial length of the eyes wearing -30D lenses (0.228±0.017) was longer than that of the eyes wearing 0D lenses (0.196±0.008). On the other hand, in the eye drop groups with an α1 blocker concentration of 0.01 (mg / mL) and an α1 blocker concentration of 0.1 (mg / mL), there was no difference in axial length between the eyes wearing -30D lenses (0.209±0.024, 0.189±0.024, respectively) and the eyes wearing 0D lenses (0.192±0.021, 0.180±0.028, respectively), and the progression of myopia was suppressed.

[0049] From the above results, it can be seen that the eye drops containing a predetermined concentration of α1 blocker show an effect of inhibiting the progression of myopia. It can be inferred that the effect of inhibiting the progression of myopia can be observed when the concentration of α1 blocker exceeds 0.001 (mg / mL), and in particular, when the concentration of α1 blocker is 0.01 (mg / mL) or more, a sufficient effect of inhibiting the progression of myopia can be confirmed.

Claims

1. An eye drop for inhibiting the progression of myopia, characterized in that: Contains an alpha 1 blocker.

2. The eye drops for inhibiting myopia progression according to claim 1, wherein: The α1 blocker salt is contained in a range of more than 0.001 mg / mL and 1.4 mg / mL or less.

3. The eye drops for inhibiting myopia progression according to claim 1 or 2, wherein: The α1 blocker is one or more selected from the group consisting of bunazosin, prazosin, urapidil, moxifloxacin and corynanthrine.

4. Use of a composition comprising an α1 blocker as an eye drop for inhibiting the progression of myopia.

5. Use of a composition comprising an α1 blocker in the manufacture of eye drops for inhibiting the progression of myopia.

6. A method for inhibiting myopia progression, comprising administering a composition comprising an α1 blocker to the eye as an eye drop for inhibiting progression.

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