Eye drops containing α1 blockers to inhibit the progression of myopia

Abstract

[Problem] To provide novel eyedrops for inhibiting myopia progression that can easily inhibit the progression of myopia simply by dropping into the eye. [Solution] This problem is solved by α1 blocker-containing eyedrops for inhibiting myopia progression. Preferably, the α1 blocker is contained in an amount of more than 0.001 mg / mL and not more than 1.4 mg / mL, in terms of an α1 blocker salt. The α1 blocker is one or more selected from among bunazosin, prazosin, urapidil, moxisylyte and corynanthine.

Description

[Technical field]

[0001] The present invention relates to an eye drop containing an α1 blocker for inhibiting the progression of myopia. [Background technology]

[0002] Myopia is particularly prevalent among Asians, especially Japanese people, and the proportion of severe myopia of -5D or more is also high. In recent years, myopia has been steadily increasing worldwide, and in Japan, the proportion of children with unaided visual acuity of less than 1.0 is increasing year by year. It is also known that myopia progresses rapidly during school age between 7 and 12 years old (see Non-Patent Document 1).

[0003] Myopia is classified into refractive myopia, accommodative myopia (pseudomyopia) and axial myopia according to the mechanism of onset, but myopia progression in school-age children is mainly axial myopia. Human eyes are hyperopic immediately after birth, and the degree of hyperopia decreases due to axial elongation during the growth period, and becomes emmetropic when entering school-age children. This axial elongation after the emmetropic phenomenon directly leads to myopia, and once the axial length has elongated, it cannot be restored to its original state. Therefore, it is considered that suppressing axial elongation during the period from the growth period to the school-age period is effective for preventing or treating myopia (see Non-Patent Document 2). In addition, the axial elongation occurs not only during the growth period but also in adults, and axial elongation in adults is said to be a risk factor for various eye diseases.

[0004] Therapeutic agents for preventing myopia have been proposed, such as Rho kinase inhibitors (see Patent Document 1), bradykinin (Patent Document 2), crocetin (Patent Document 3), etc. The present inventor has also proposed an eye drop for suppressing myopia, which contains bunazosin (Patent Document 4). [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Medical Progress, Vol. 253, No. 2, 2015. [Non-Patent Document 2] Ophthalmology, Vol. 58, No. 6, 635-641, 2016. [Patent documents]

[0006] [Patent Document 1] WO2010 / 010702 [Patent Document 2] JP 2011-144111 A [Patent Document 3] WO2018 / 212152 [Patent Document 4] Patent No. 6917103 Summary of the Invention [Problem to be solved by the invention]

[0007] An 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 a simple means. [Means for solving the problem]

[0008] The eye drop for inhibiting the progression of myopia according to the present invention is characterized in that it contains an α1 blocker. The α1 blocker is preferably contained in a range of more than 0.001 mg / mL and not more than 1.4 mg / mL as an α1 blocker salt. The α1 blocker is preferably one or more selected from bunazosin, prazosin, urapidil, moxisilt, and corinanthin. Effect of the Invention

[0009] According to the present invention, the progression of myopia can be suppressed by a myopic patient simply administering eye drops to the eye, without the need for a doctor to give an injection at a medical institution. [Brief description of the drawings]

[0010] [Figure 1] This is a photograph of a mouse used in a myopia induction experiment (with a -30D lens attached to the right eye and a 0D lens attached to the left eye). [Diagram 2](Experiment 1) These are the results of refraction when eye drops containing bunazosin, prazosin, and urapidil as alpha-1 blockers were instilled into myopic and non-myopic eyes. [Diagram 3] (Experiment 1) These are the results of axial length when eye drops containing bunazosin, prazosin, and urapidil as alpha-1 blockers were instilled into myopic and non-myopic eyes. [Figure 4] (Experiment 2) These are the results of refraction when eye drops with different alpha-1 blocker contents were instilled into myopic and non-myopic eyes. [Diagram 5] (Experiment 2) These are the results of axial length when eye drops containing different amounts of α1 blocker were instilled into myopic and non-myopic eyes. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The present invention relates to an ophthalmic solution for inhibiting the progression of myopia, which contains an α1 blocker. The present invention is not limited to the following embodiments and examples, and includes various modifications and applications within the scope of the present invention.

[0012] In the ongoing research by the present inventors into the inhibition of myopia progression, the present invention provides an α1 blocker-containing eye drop that can inhibit the progression of myopia by a simple method in which the myopic patient instills the eye drop into their eye, without the need for a doctor to directly inject the eye into the patient's eye at a medical institution. In this application, as in the experimental example described below, a liquid eye drop containing an α1 blocker was instilled into a mouse myopia model, and the refractive index and axial length were evaluated to verify the effect of inhibiting the progression of myopia.

[0013] The eye drops are usually liquid eye drops (also called eye drops) provided in an eye drop container. Such eye drops can be easily applied to the eyes by the myopic person himself. Examples of α-1 blockers contained in the eye drops include bunazosin, prazosin, urapidil, moxisilt, corinanthin, etc., and one or more of these are contained.

[0014] The content of the α1 blocker is preferably in the range of more than 0.001 mg / mL and not more than 1.4 mg / mL. As shown in Experiment 2 described later, the content of the α1 blocker salt is particularly preferably 0.01 mg / mL or more. The dosage and administration of the eye drops vary depending on the symptoms, age, etc. of the patient, but usually, about 1 to 2 drops may be instilled about 1 to 6 times a day. The upper limit of the content is not particularly limited, but in this application, a realistic upper limit concentration is set according to the solubility of the α1 blocker salt used. For example, the solubility in water is 7.7 to 9.1 mg / mL for bunazosin hydrochloride, 1.4 mg / mL for prazosin hydrochloride, 25 mg / mL for urapidil hydrochloride, and about 5 mg / mL for doxazosin hydrochloride, so taking these into consideration, 1.4 mg / mL is set as the upper limit of the α1 blocker salt.

[0015] Other components that may be included in the eye drops include pharmacologically active components, physiologically active components, eye drops for glaucoma, etc., and these may be included within the scope of the present invention without impairing the effects of the present invention. The eye drops may further include one or more of various other components and additives as necessary, according to the usual method, depending on the purpose and form of the eye drops, within the scope of the present invention without impairing the effects of the present invention. Examples of such components and additives include various additives such as fragrances or refreshing agents, preservatives, bactericides or antibacterial agents, pH regulators, chelating agents, stabilizers, isotonicity agents, and buffers. By adding an α1 blocker to a known eye drop, the effect of suppressing the progression of myopia can be further enhanced.

[0016] As described above, the present invention is an eye drop for inhibiting the progression of myopia that contains an α1 blocker, but the present invention can also be expressed in other invention categories such as (i) use of a composition containing an α1 blocker as an eye drop for inhibiting the progression of myopia, (ii) use of a composition containing an α1 blocker for the manufacture of an eye drop for inhibiting the progression of myopia, (iii) a method for inhibiting the progression of myopia by instilling a composition containing an α1 blocker as an eye drop for inhibiting progression, etc. Note that the "myopia progression inhibiting effect" in this application refers to the effect of inhibiting the progression of axial myopia. EXAMPLES

[0017] The following experiments further illustrate the invention.

[0018] [measurement] As shown in Figure 1, 3-week-old mice (C57BL6 / J, CLEA Japan, Inc.) were fitted with a 0D lens ("D" stands for Diopter, a unit of lens refractive power) in the left eye and a -30D lens in the right eye, and myopia was induced for 3 weeks. During the myopia induction period, eye drops were administered once a day. PBS (Phosphate Buffered Saline) was administered as the control group, and α1 blocker eye drops were administered as the test group. Bunazosin, prazosin, and urapidil were used as α1 blockers.

[0019] After 3 weeks, the refractive index and axial length of the mouse eyeball were measured and the amount of change was calculated. Refraction values ​​were measured using an infrared photorefractor for mice (made by Professor Schaeffel of the University of Tubingen). The more negative the refractive index, the more myopic the patient. Axial length was measured using a spectral domain optical coherence tomography (Envisu R4310, Leica). The larger the axial length value, the more myopic the patient.

[0020] [Experiment 1] (Experimental Method) The eye drops used were PBS (control group), Bunazosin eye drops (bunazosin hydrochloride 0.1 mg / mL), Prazosin eye drops (prazosin hydrochloride 0.1 mg / mL), and Urapidil eye drops (urapidil hydrochloride 0.1 mg / mL). Eye drops were administered once a day for 3 weeks during the myopia induction period.

[0021] (Experimental Results) Figure 2 shows the results of refractive index. In the control group (PBS), eyes wearing -30D lenses (-14.05 ± 3.71) became more myopic than eyes wearing 0D lenses (2.55 ± 2.74). On the other hand, in the α1 blocker eye drop group, the difference between eyes wearing -30D lenses (-0.74 ± 4.07, -2.03 ± 5.33, -5.51 ± 6.29, respectively) and eyes wearing 0D lenses (3.65 ± 4.72, 3.97 ± 2.34, 0.33 ± 7.07, respectively) was small for all bunazosin, prazosin, and urapidil, and the progression of myopia was suppressed.

[0022] Figure 3 shows the results for axial length. In the control group (PBS), the axial length of the eyes wearing -30D lenses (0.227 ± 0.015) was longer than that of the eyes wearing 0D lenses (0.190 ± 0.014). On the other hand, in the α1 blocker eye drop group, the difference in axial length between the eyes wearing -30D lenses (0.191 ± 0.026, 0.200 ± 0.018, 0.233 ± 0.020, respectively) and the eyes wearing 0D lenses (0.187 ± 0.019, 0.190 ± 0.014, 0.217 ± 0.014, respectively) was small for all bunazosin, prazosin, and urapidil, and the progression of myopia was suppressed.

[0023] These results indicate that eye drops containing an α1 blocker are effective in inhibiting the progression of myopia.

[0024] [Experiment 2] (Experimental Method) The α1 blocker eye drops were used with concentrations (mg of α1 blocker salt in 1 mL: mg / mL) of 0.001 (mg / mL), 0.01 (mg / mL), and 0.1 (mg / mL). Each eye drop was administered once a day for three weeks during the myopia induction period. The control group received PBS eye drops that did not contain an α1 blocker, and the α1 blocker eye drops contained a specified concentration of bunazosin hydrochloride.

[0025] (Experimental Results) Figure 4 shows the results of refractive index. In the PBS (control group) (α1 blocker concentration: 0 mg / mL), eyes wearing -30D lenses (-13.59 ± 3.35) were more myopic than eyes wearing 0D lenses (2.06 ± 2.02). Even in the group of instilled α1 blocker at a concentration of 0.001 (mg / mL), eyes wearing -30D lenses (-10.90 ± 4.13) were more myopic than eyes wearing 0D lenses (-0.33 ± 3.47), and although the progression of myopia was slightly suppressed compared to the PBS (control group) (α1 blocker concentration: 0 mg / mL), and some effect in suppressing myopia progression was observed, the effect in suppressing myopia progression was not sufficient compared to when the α1 blocker concentration was 0.01 (mg / mL) or higher. Therefore, even if an α1 blocker concentration of 0.001 (mg / mL) is not sufficient, it was easy to infer that an α1 blocker concentration of more than 0.001 (mg / mL) would have an effect of suppressing myopia progression.On the other hand, in the groups in which α1 blocker concentrations of 0.01 (mg / mL) and 0.1 (mg / mL) were instilled, the difference between the eyes wearing -30D lenses (-6.92 ± 4.08 and -1.26 ± 3.28, respectively) and the eyes wearing 0D lenses (-0.83 ± 3.20 and 3.19 ± 3.76, respectively) was small, and the progression of myopia was suppressed.

[0026] Figure 5 shows the results 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). Even in the group that received α1 blocker at a 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 groups that received eye drops containing an alpha-1 blocker at a concentration of 0.01 (mg / mL) and an alpha-1 blocker at a concentration of 0.1 (mg / mL), there was no difference in axial length between the eyes that wore -30D lenses (0.209±0.024 and 0.189±0.024, respectively) and the eyes that wore 0D lenses (0.192±0.021 and 0.180±0.028, respectively), and the progression of myopia was suppressed.

[0027] These results indicate that eye drops containing a certain concentration of α1 blockers are effective in inhibiting the progression of myopia. It can be inferred that an α1 blocker concentration of over 0.001 (mg / mL) is effective in inhibiting the progression of myopia, and a sufficient effect in inhibiting the progression of myopia was confirmed, particularly when the α1 blocker concentration was 0.01 (mg / mL) or higher.

Claims

1. An eye drop for inhibiting the progression of myopia, comprising prazosin or urapidil.

2. Use of a composition containing prazosin or urapidil for the manufacture of an eye drop for inhibiting the progression of myopia.

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