Ophthalmic components
An ophthalmic composition with azulene sulfonic acid and cyanocobalamin targets extraocular muscles to treat and prevent fatigue, addressing the inadequacies of existing compositions by delivering active ingredients directly to the muscles, thereby reducing inflammation and alleviating symptoms.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-09-30
- Publication Date
- 2026-04-09
AI Technical Summary
Existing ophthalmic compositions fail to directly target and treat or prevent fatigue of the extraocular muscles, which are prone to strain due to prolonged use of digital devices.
An ophthalmic composition containing azulene sulfonic acid, cyanocobalamin, or their salts, which can directly reach and act on the extraocular muscles to alleviate fatigue.
The composition effectively treats and prevents extraocular muscle fatigue by delivering active ingredients to the muscles, reducing inflammation and alleviating symptoms such as eye strain.
Smart Images
Figure 2026061540000005 
Figure 2026061540000001 
Figure 2026061540000002
Abstract
Description
Technical Field
[0001] The present disclosure relates to an ophthalmic composition.
Background Art
[0002] In recent years, with the spread of personal computers, the increase in VDT work, and the lengthening of the operation time of smartphones and tablets, the time of continuously looking at displays has been increasing along with the changes in lifestyle. It is known that continuously looking at a display for a long time causes continuous tension in the extraocular muscles that control eye movement, and excessive burden on the muscles around the eyes, which easily causes eye fatigue (fatigue of the eyes, fatigue of the eye muscles). Such eye fatigue is an unpleasant symptom caused by visual work. Although various causes have been reported, many are due to overuse of the eyes, especially often caused by facing digital devices such as personal computers and smartphones.
[0003] Neostigmine methylsulfate and cyanocobalamin are known to act on the ciliary body and improve accommodative asthenopia (see, for example, Non-Patent Documents 1 and 2).
Prior Art Documents
Non-Patent Documents
[0004]
Non-Patent Document 1
Non-Patent Document 2
[0005] However, few ophthalmic compositions were known that could reach and directly act on the extraocular muscles to treat or prevent their fatigue.
[0006] Therefore, the object of this disclosure is to provide an ophthalmic composition that can directly reach the extraocular muscles and treat or prevent their fatigue. [Means for solving the problem]
[0007] This disclosure provides an ophthalmic composition containing one or more compounds selected from the group consisting of azulene sulfonic acid, cyanocobalamin, and salts thereof, wherein the compounds reach the extraocular muscles.
[0008] The above ophthalmic composition is preferably used for the treatment and / or prevention of fatigue of the extraocular muscles.
[0009] The extraocular muscle mentioned above is preferably the medial rectus muscle.
[0010] Furthermore, this disclosure provides an ophthalmic composition containing one or more compounds selected from the group consisting of azulene sulfonic acid, cyanocobalamin, and salts thereof, for use in the treatment and / or prevention of extraocular muscle fatigue. [Effects of the Invention]
[0011] The ophthalmic compositions of this disclosure can directly reach the extraocular muscles and treat or prevent their fatigue. [Brief explanation of the drawing]
[0012] [Figure 1] This graph shows the evaluation results of TNF-α expression levels performed in Example 2. [Modes for carrying out the invention]
[0013] [Ophthalmic composition] An ophthalmic composition according to one embodiment of the present disclosure comprises at least one selected from the group consisting of azulene sulfonic acid, cyanocobalamin, and salts thereof. That is, the ophthalmic composition comprises one or more of azulene sulfonic acid, cyanocobalamin, and salts thereof as active ingredients.
[0014] Examples of azulene sulfonic acid salts include alkali metal salts. Examples of alkali metal salts include sodium salts and potassium salts. Preferred azulene sulfonic acid and its alkali metal salts are azulene sulfonic acid and alkali metal salts of azulene sulfonic acid, more preferably azulene sulfonic acid and sodium azulene sulfonate, and even more preferably sodium azulene sulfonate.
[0015] The above ophthalmic composition is particularly preferable to contain azulene sulfonic acid or a salt thereof and cyanocobalamin or a salt thereof, from the viewpoint of being particularly excellent in treating or preventing fatigue of the extraocular muscles.
[0016] The content of azulene sulfonic acid and / or its salts in the above ophthalmic composition (total content if two or more types are included) is preferably 0.0004 to 0.5 w / v%, more preferably 0.001 to 0.1 w / v%, even more preferably 0.004 to 0.05 w / v%, even more preferably 0.01 to 0.02 w / v%, and most preferably 0.02 w / v% based on the total amount (100 vol.%) of the ophthalmic composition.
[0017] The content of cyanocobalamin and / or its salts in the above ophthalmic composition (total content if two or more types are included) can be 0.0001 to 0.5 w / v%, preferably 0.0005 to 0.1 w / v%, more preferably 0.001 to 0.05 w / v%, even more preferably 0.004 to 0.02 w / v%, and most preferably 0.02 w / v% based on the total amount (100 vol.%) of the ophthalmic composition.
[0018] The ratio of cyanocobalamin and / or its salt to azulene sulfonic acid and / or its salt in the above ophthalmic composition is preferably 0.001 to 1000 parts by weight, more preferably 0.01 to 100 parts by weight, even more preferably 0.1 to 10 parts by weight, particularly preferably 0.5 to 5 parts by weight, and most preferably 1 part by weight, per 1 part by weight of azulene sulfonic acid and / or its salt.
[0019] The above ophthalmic composition may contain other components in addition to the various components described above. Examples of these other components include those that may be included in public or conventional ophthalmic compositions, such as polyhydric alcohols, cooling agents, inorganic salts, salts of organic acids, acids, bases, isotonic agents, antioxidants, and vitamins. Examples of polyhydric alcohols include propylene glycol, glycerin, glucose, mannitol, sorbitol, xylitol, and trehalose. Examples of cooling agents include menthol and camphor. Examples of inorganic salts include borax, sodium bicarbonate, sodium hydrogen phosphate, and anhydrous sodium dihydrogen phosphate. Examples of salts of organic acids include sodium citrate. Examples of acids include boric acid, phosphoric acid, citric acid, sulfuric acid, acetic acid, and hydrochloric acid. Examples of bases include sodium hydroxide, potassium hydroxide, trometamol, and monoethanolamine. Examples of the isotonic agents mentioned above include sodium chloride, potassium chloride, and the polyhydric alcohols mentioned above. Examples of the antioxidants mentioned above include tocopherol acetate and dibutylhydroxytoluene.
[0020] The pH of the above ophthalmic composition is preferably 3 or more, more preferably 4 or more, even more preferably 5 or more, and even more preferably 5.5 or more. It can also be 6 or more. Also, it is preferably 10 or less, more preferably 9 or less, even more preferably 8.5 or less, and particularly more preferably 8 or less. Within the above range, irritation to the eye can be suppressed and the above effects of the present invention can be obtained.
[0021] The osmotic pressure ratio of the above ophthalmic composition is preferably 0.4 or more, more preferably 0.6 or more, and even more preferably 0.85 or more. Also, it is preferably 5 or less, more preferably 3 or less, even more preferably 2 or less, and particularly preferably 1.55 or less. Within the above range, irritation to the eye can be suppressed and the above effects of the present invention can be obtained. The above osmotic pressure ratio is the ratio of the osmotic pressure of the sample to the osmotic pressure of 286 mOsm (0.9 w / v% sodium chloride aqueous solution) based on the 17th revised Japanese Pharmacopoeia. The above osmotic pressure is measured according to the osmotic pressure measurement method (freezing point depression method) described in the 17th revised Japanese Pharmacopoeia. For the standard solution for measuring the osmotic pressure ratio (0.9 w / v% sodium chloride aqueous solution), sodium chloride (Japanese Pharmacopoeia standard reagent) is dried at 500 - 650 °C for 40 - 50 minutes, then cooled in a desiccator (silica gel), 0.900 g of it is accurately weighed, dissolved in purified water and made up to exactly 100 mL, or a commercially available standard solution for measuring the osmotic pressure ratio (0.9 w / v% sodium chloride aqueous solution) is used.
[0022] Examples of the above ophthalmic composition include eye drops (also referred to as eye drops or eye medications. Eye drops include those that can be instilled during contact lens wear), eye washes, eye ointments (water-soluble eye ointments, oil-soluble eye ointments), contact lens solutions, intraocular injections (e.g., intravitreal injections), solutions for contact lenses (cleaning solutions, preservation solutions, disinfecting solutions, multipurpose solutions, package solutions), preservatives for excised eye tissues such as corneas for transplantation, and perfusion fluids during surgery. Eye drops, eye washes, and eye ointments also include those used during contact lens wear.
[0023] The "contact lens" includes hard contact lenses, soft contact lenses (including both ionic and non-ionic, including both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses).
[0024] The above ophthalmic composition is preferably an eye drop, eye wash, eye ointment (water-soluble eye ointment, oil-soluble eye ointment), contact lens wearing solution, contact lens solution (cleaning solution, storage solution, disinfecting solution, multipurpose solution, package solution), more preferably an eye drop, eye wash, contact lens wearing solution, contact lens solution (cleaning solution, storage solution, disinfecting solution, multipurpose solution), still more preferably an eye drop and an eye wash, and particularly preferably an eye drop.
[0025] When the above ophthalmic composition is an eye wash, its usage varies depending on the target symptoms. For example, it can be used once or more, twice or more, three times or more, four times or more, five times or more, or six times or more per day. Also, it can be used nine times or less, eight times or less, seven times or less, six times or less, five times or less, or four times or less per day.
[0026] When the above ophthalmic composition is an eye drop, the ophthalmic composition containing each component at the above concentration can be instilled, for example, 1 to 3 drops per application, preferably 1 to 2 drops per application. It can also be 1 drop.
[0027] When the above ophthalmic composition is an eye wash, the eye wash containing each component at the above concentration can be used for eye washing, for example, 1 to 30 mL per application, preferably 1 to 20 mL, and still more preferably 4 to 6 mL per application.
[0028] When the above ophthalmic composition is a contact lens wearing solution, at the time of wearing and removing the contact lens, for example, 1 to 3 drops, preferably 1 to 2 drops, can be dropped on one side and / or both sides of the contact lens per application, and then the contact lens can be worn after wetting. Preferably, it is worn after wetting both sides of the contact lens.
[0029] If the above-mentioned ophthalmic composition is a contact lens solution, it may, for example, be left in contact with the contact lens for 1 hour or more, 2 hours or more, 4 hours or more, or 1 day or more. Alternatively, it may be left in contact for 30 days or less, 14 days or less, 7 days or less, or 2 days or less.
[0030] The above ophthalmic composition may be used while wearing contact lenses or while not wearing contact lenses.
[0031] The above ophthalmic composition, when instilled into the eye, delivers one or more compounds selected from the group consisting of azulene sulfonic acid, cyanocobalamin, and salts thereof to the extraocular muscles. By reaching the extraocular muscles, the above ophthalmic composition can treat or prevent fatigue of the extraocular muscles. Therefore, the above ophthalmic composition is preferably used for the treatment and / or prevention of fatigue of the extraocular muscles. Generally, it has been reported that fatigue of skeletal muscles can be alleviated by suppressing inflammatory cytokines (for example, Japanese Patent Publication No. 2017-031120). For this reason, the treatment and / or prevention of fatigue of extraocular muscles, which are composed of skeletal muscle, is preferably achieved through an anti-inflammatory effect on the extraocular muscles.
[0032] Examples of the extraocular muscles mentioned above include the superior rectus, inferior rectus, medial rectus, lateral rectus, inferior oblique, and superior oblique muscles of the eye. The ophthalmic composition may reach only one of the extraocular muscles or two or more. In particular, it is preferable that it reaches at least the medial rectus muscle.
[0033] Furthermore, treating and / or preventing fatigue of the extraocular muscles mentioned above can treat and / or prevent eye strain, ophthalmia caused by ultraviolet rays or other light (such as snow blindness), conjunctival congestion, blepharitis (inflammation of the eyelids), blurred vision (such as when there is excessive eye discharge), discomfort when wearing hard contact lenses, prevention of eye diseases (such as after swimming or when dust or sweat gets into the eyes), and itchy eyes. Examples of eye strain (fatigue) mentioned above include that caused by VDT work and the use of digital devices. [Examples]
[0034] An embodiment of this disclosure will be described in more detail below based on examples.
[0035] Preparation example (Preparation of ophthalmic compositions) Using phosphate-buffered saline as the standard composition, various ophthalmic compositions were prepared by conventional methods by adding various additives (Azulene Sulfonate: sodium azulene sulfonate, Cyanocobalamin: cyanocobalamin) to phosphate-buffered saline (PBS) as shown in Table 1.
[0036] Example 1 Male Japanese white rabbits (JW) aged 7-12 weeks were administered 50 μL of various ophthalmic compositions prepared in the example without anesthesia, and then euthanized by hemorrhage. The eyeballs were removed, washed with approximately 20 mL of physiological saline, and the medial rectus muscle was collected as a sample. The time from instillation of the ophthalmic composition to sample collection was approximately 15 minutes. After washing, the collected medial rectus muscle was weighed and stored. Subsequently, the homogenized medial rectus muscle solution was subjected to liquid chromatography to measure the concentrations of various components. The results are shown in Table 1.
[0037] The conditions for liquid chromatography are as follows. The concentrations of the various components shown in Table 1 were calculated by creating a calibration curve using the concentration ratio versus the peak area ratio, and then determining the ratio of each peak area to the total peak area. The detection limit was 1 ng / g. In the table, "#of sample" indicates the number of samples; if it is 3, the average value is used as the result. Device: Product name "Xevo TQ Absolute", manufactured by Waters Corporation Product name: "ACQUITY Premier I-CLASS Systems", manufactured by Waters Corporation. Column: Product name "IM-column InertSustain C18", manufactured by GL Sciences Co., Ltd. Flow rate: 750μL / min Mobile phase: Water, methanol
[0038] [Table 1]
[0039] As shown in Table 1, both sodium azulene sulfonate and cyanocobalamin were detected in the medial rectus muscle at concentrations of 0.02% and 0.2% by mass of the ophthalmic composition. Therefore, it was confirmed that sodium azulene sulfonate and cyanocobalamin reached the medial rectus muscle.
[0040] Example 2 <Investigation of the anti-inflammatory effects of sodium azulene sulfonate and cyanocobalamin in human corneal epithelial cell lines (HCE-T)> 5 x 10 in a 24-well plate 4Human corneal epithelial cell line (HCE-T, Cell Materials Development Laboratory, BioResource Research Center, RIKEN), seeded to a density of cells / well, was cultured for approximately 48 hours at 37°C under 5% CO2 conditions using DMEM / F12 and HEPES (Thermo Fisher) with the additives shown in Table 2. The supernatant was then removed. Next, 990 μL of each reagent solution, prepared at the concentrations shown in Table 4, was added to each well, and the cells were cultured for 1 hour at 37°C under 5% CO2 conditions. After 1 hour of culture, 10 μL of 10 mg / mL Lipopolysaccharides (Sigma-Aldrich) was added to each well, and the cells were cultured for 6 hours at 37°C under 5% CO2 conditions. Cells were then harvested and quantitative real-time PCR was performed to evaluate the TNF-α expression levels shown in Table 3. The TNF-α results are shown in Figure 1.
[0041] [Table 2]
[0042] [Table 3]
[0043] [Table 4]
[0044] As shown in Figure 1, the test solution containing azulene sulfonic acid alone (0.02%) showed suppression of TNF-α expression compared to groups 1 and 2. Furthermore, the test solution prepared by combining sodium azulene sulfonate and cyanocobalamin in a 1:1 ratio (0.02%) also showed suppression of TNF-α expression compared to the test solution containing sodium azulene sulfonate alone. Sodium azulene sulfonate was also effective in treating and / or preventing extraocular muscle fatigue, and the mixture of sodium azulene sulfonate and cyanocobalamin was considered to be even more effective.
[0045] The following describes variations of the invention relating to this disclosure. [Note 1] Contains one or more compounds selected from the group consisting of azulene sulfonic acid, cyanocobalamin, and salts thereof. An ophthalmic composition in which the compound reaches the extraocular muscles. [Note 2] An ophthalmic composition as described in Note 1, used for the treatment and / or prevention of fatigue of the extraocular muscles. [Note 3] The ophthalmic composition according to Note 1 or 2, wherein the extraocular muscle is the medial rectus muscle. [Note 4] An ophthalmic composition according to any one of Notes 1 to 3, comprising azulene sulfonic acid or a salt thereof and cyanocobalamin or a salt thereof. [Note 5] An ophthalmic composition containing one or more compounds selected from the group consisting of azulene sulfonic acid, cyanocobalamin, and salts thereof, used for the treatment and / or prevention of extraocular muscle fatigue. [Note 6] The ophthalmic composition described in Note 5, comprising azulene sulfonic acid or a salt thereof and cyanocobalamin or a salt thereof. [Note 7] An ophthalmic composition containing one or more compounds selected from the group consisting of azulene sulfonic acid, cyanocobalamin, and salts thereof, used for the treatment and / or prevention of extraocular muscle fatigue. [Note 8] An ophthalmic composition containing one or more compounds selected from the group consisting of azulene sulfonic acid, cyanocobalamin, and salts thereof, used for the treatment and / or prevention of eye fatigue. [Note 9] An ophthalmic composition according to any one of Notes 1 to 8, used for the treatment and / or prevention of fatigue caused by VDT work and / or the use of digital devices. [Note 10] An ophthalmic composition containing one or more compounds selected from the group consisting of azulene sulfonic acid, cyanocobalamin, and salts thereof, for use in treating eye and / or extraocular muscle fatigue caused by VDT work or use of digital devices.
Claims
1. It contains one or more compounds selected from the group consisting of azulene sulfonic acid, cyanocobalamin, and salts thereof. An ophthalmic composition in which the compound reaches the extraocular muscles.
2. An ophthalmic composition according to claim 1, used for the treatment and / or prevention of fatigue of the extraocular muscles.
3. The ophthalmic composition according to claim 1 or 2, wherein the extraocular muscle is the medial rectus muscle.
4. An ophthalmic composition containing one or more compounds selected from the group consisting of azulene sulfonic acid, cyanocobalamin, and salts thereof, used for the treatment and / or prevention of extraocular muscle fatigue.
5. An ophthalmic composition containing one or more compounds selected from the group consisting of azulene sulfonic acid, cyanocobalamin, and salts thereof, used for the treatment and / or prevention of eye fatigue.
6. The ophthalmic composition according to claim 1, 4, or 5, which is also suitable for the treatment and / or prevention of fatigue caused by VDT work and / or the use of digital devices.