JP7009094B2 - Oil-based eye drops - Google Patents

Description

The present invention relates to oil-based eye drops.

It has been known that castor oil can be added to eye drops (Patent Document 1). Further, it has been known that vitamin A and vitamin E can also be added to eye drops.

However, vitamins A and E have the characteristics of being adsorbed on a container for eye drops and being unstable to light and heat and easily decomposed. Therefore, it is important to leave vitamin A and vitamin E in a higher proportion in the eye drops even when the container is filled.

Japanese Unexamined Patent Publication No. 2000-273061

Therefore, the present invention provides an oily eye drop that contains castor oil and vitamins A and / or vitamin E, but can retain vitamin A and / or vitamin E in a higher proportion. The purpose is to provide.

When the present inventor made a diligent study in view of the above problems, a case where vitamins A and E and vitamin oil were mixed and the obtained mixture was filled in a container made of polyethylene terephthalate or a container made of polypropylene. , It has been found that vitamins A and E can remain in the mixture in a higher proportion. The present invention has been completed as a result of further studies based on the findings, and is as follows.

Item 1. Oil-based eye drops filled in polyethylene terephthalate or polypropylene containers,
Here, the oily eye drop contains castor oil, at least one selected from the group consisting of vitamins A and E, and 0 to 8% by mass of water.

Item 2. Item 2. The oil-based eye drop according to Item 1, wherein the oil-based eye drop further contains l-menthol.

Item 3. Item 2. The oil-based eye drop according to Item 1 or 2, wherein the oil-based eye drop further contains dibutylhydroxytoluene.

Item 4. Item 2. The oil-based eye drop according to any one of Items 1 to 3, wherein the color of the container is orange.

According to the present invention, vitamins A and E are mixed with perilla oil, and the obtained mixture is filled in a container made of polyethylene terephthalate or a container made of polypropylene, whereby vitamin As are contained in the mixture. And vitamin E can be retained in a higher proportion.

The present invention is an oil-based eye drop filled in a container made of polyethylene terephthalate or polypropylene, and castor oil, at least one selected from the group consisting of vitamins A and E, and water 0 to 0 to. The present invention relates to an oil-based eye drop containing 8% by mass.

Castor oil is a fatty oil obtained from the seeds of castor oil (Ricinus communis) and is a conventionally known oil. Castor oil is not limited as long as it is pharmaceutically or cosmetically acceptable.

The content of castor oil is not limited, but 10% by mass or more is exemplified in the oil-based eye drops, preferably 20 to 99.99% by mass, more preferably 30 to 99.99% by mass, and further preferably 40 to 99. An example is .99% by mass, more preferably 50 to 99.99% by mass, particularly preferably 60 to 99.99% by mass, and particularly more preferably 70 to 99.99% by mass. In the oil-based eye drops of the present invention, the content of castor oil is not limited to this extent, but is more preferably 80 to 99.99% by mass, still more preferably 90 to 99.99% by mass, and even more preferably 95 to 99. An example is .99% by mass, particularly preferably 98 to 99.99% by mass, and particularly more preferably 99 to 99.99% by mass.

The vitamin A is not limited as long as it is pharmaceutically or cosmetically acceptable, and is limited to retinol, retinol palmitate, retinyl acetate, retinal, retinoic acid, methyl retinoate, ethyl retinoate, retinol retinoate, and vitamin A. Examples thereof include fatty acid esters, d-δ-tocopheryl retinoate, α-tocopheryl retinoate, and β-tocopheryl retinoate. Examples of the vitamin A are preferably retinyl palmitate and retinyl acetate, and more preferably retinyl palmitate.

The vitamin A may be contained in the vitamin A oil, and conventionally known vitamin A oils can be used. Examples of the vitamin A oil include those obtained by adding vegetable oil to the vitamin A, diluted products thereof, concentrates and the like. Although not limiting the present invention, as the vitamin A oil, those containing 3000 IU or more of vitamin A per 1 g of the vitamin A oil are preferably exemplified. Regarding the content of the vegetable oil to be added, if the vegetable oil is castor oil, this is added to the content of the castor oil, and if the vegetable oil is an oil other than castor oil, this is the content of the oily component described later. Is added up to.

These may be used alone or in combination of two or more.

The content of vitamin A is not limited, but is preferably 10,000 to 70,000 IU, more preferably 30,000 to 70,000 IU, still more preferably 40,000 to 70,000 IU in 100 g of oil-based eye drops. Particularly preferably, 50,000 to 70,000 IU are exemplified.

Vitamin Es are not limited to the extent pharmaceutically or cosmetically acceptable, and examples thereof include tocopherols, tocotrienols, derivatives thereof, and salts thereof. The tocopherol and tocotrienol may be any of α-, β-, γ-, and δ-, and may be any of d-form and dl-form.

Examples of vitamin E include tocopherol, a derivative thereof, and salts thereof. Examples of the derivative of tocopherol include tocopherol organic acid esters such as tocopherol acetate, tocopherol succinate, tocopherol nicotinate, and tocopherol linolenate. The derivative of these tocopherols may be either d-form or dl-form.

These may be used alone or in combination of two or more.

Although the content of vitamin E is not limited, it is preferably 0.005 to 0.5% by mass, more preferably 0.005 to 0.05% by mass, and further preferably 0.01 to 0% by mass in the oil-based eye drops. 05% by mass is exemplified.

The oil-based eye drops of the present invention may contain either vitamin A or vitamin E, or may contain both of them.

The oil-based eye drops of the present invention may or may not contain water, but when water is contained, the content thereof is 8% by mass or less. From this, the content of water in the oil-based eye drops of the present invention is 0 to 8% by mass, preferably 0 to 5% by mass, more preferably 0 to 3% by mass, still more preferably 0 to 2% by mass. Further preferably, 0 to 1% by mass, particularly preferably 0 to 0.5% by mass, particularly more preferably 0 to 0.3% by mass, still particularly preferably 0% by mass is exemplified.

The oil-based eye drops of the present invention may optionally contain an oil-based component other than castor oil (hereinafter, "oil-based component" means "oil-based component other than castor oil" in the present specification). The oily component is not limited as long as it is pharmaceutically or cosmetically acceptable, but uikyo oil, peppermint oil, bergamot oil, eucalyptus oil, sesame oil, soybean oil, rapeseed oil, corn oil, camellia oil, lacquer oil, Examples thereof include animal and vegetable fats and oils such as almond oil, wheat germ oil, sunflower oil, cottonseed oil, olive oil, rose oil, and Benibana oil, liquid paraffin, vaseline, macrogol 4000, and macrogol 6000. Preferred oily components include fennel oil, peppermint oil, bergamot oil, eucalyptus oil, liquid paraffin, petrolatum, macrogol 4000, macrogol 6000 and the like.

These may be used alone or in combination of two or more.

The content of the oily component is also not limited, but when the oily eye drops of the present invention contain the oily components, 0.0001 to 50% by mass, preferably 0.0001 to 40% by mass, more preferably 0.0001 to 40% by mass in the oily eye drops. 0.0001 to 30% by mass, still more preferably 0.0001 to 20% by mass, even more preferably 0.0001 to 10% by mass, particularly preferably 0.0001 to 8% by mass, and particularly more preferably 0.0001 to 0.0001. 5% by mass, more particularly 0.0001 to 3% by mass is exemplified.

In addition to the above-mentioned components, the oil-based eye drops of the present invention may further contain any other pharmaceutically or cosmetically acceptable component. Optional ingredients include surfactants, pH regulators, buffers, solubilizers, preservatives, thickeners, stabilizers, thickeners, antioxidants, dispersants, isotonic agents, chelates. Agents, refreshing agents, coloring agents, fragrances, various useful ingredients (anti-allergic agents, antihistamines, focus control function improving agents, anti-inflammatory agents, astringent agents, antibacterial agents, corneal protective agents, decongestants, amino acids, vitamins (vitamins) (Other than A and Vitamin E), etc.), etc. are exemplified.

Although not limiting the present invention, l-menthol is mentioned as an example of any component. When the oil-based eye drops of the present invention contain l-menthol, the content thereof is preferably 0.005 to 1% by mass, more preferably 0.01 to 0.5% by mass, still more preferably in the oil-based eye drops. Is 0.02 to 0.5% by mass, more preferably 0.05 to 0.5% by mass, particularly preferably 0.08 to 0.5% by mass, and particularly more preferably 0.1 to 0.5% by mass. %, More particularly preferably 0.2 to 0.5% by mass.

Further, although not limiting the present invention, dibutylhydroxytoluene is mentioned as an example of any component. When the oil-based eye drops of the present invention contain dibutylhydroxytoluene, the content thereof is preferably 0.0001 to 0.05% by mass, more preferably 0.0005 to 0.05% by mass in the oil-based eye drops. More preferably, 0.005 to 0.05% by mass is exemplified.

In the oil-based eye drops of the present invention, any component may be used alone or in combination of two or more, and the content thereof may be appropriately set according to the purpose and the like. ..

The oily eye drops of the present invention can be produced by mixing castor oil, at least one selected from the group consisting of vitamins A and E, and water, oily components, and arbitrary components as necessary. ..

The form of the oil-based eye drop of the present invention is not limited, and liquid, milky liquid, gel-like, etc. are exemplified at room temperature (24 ° C.), preferably liquid, milky liquid, and more preferably liquid.

Further, the oil-based eye drop of the present invention is clear and may be colored or colorless as long as it is used.

The viscosity of the oil-based eye drop of the present invention is not limited as long as it can be used as an eye drop, but is preferably 50 to 800 cp at 24 ° C., more preferably 200 to 700 cp, and further preferably 300 to 650 cp. .. For the viscosity, a spindle F was used in a Brookfield viscometer (LVDV-II +) (manufactured by Brookfield Engineering Labs), and the screw tube No. 7 (35 × 78, manufactured by Maruel Co., Ltd.) is filled with 50 g of oil-based eye drops, and the viscosity is 5 minutes after the start of measurement at a rotation speed of 4 rpm and 24 ° C.

The pH of the oil-based eye drop of the present invention is also not limited as long as it can be used as an eye drop, but pH 5.5 to 8, preferably pH 6 to 7.5 at 24 ° C. is exemplified. The pH is measured with a desktop pH meter F-52 (manufactured by HORIBA, Ltd.).

The oily eye drops of the present invention are used for tired eyes, blurred eyes, itchy eyes, congestion, dry eyes, eye inflammation (snow eyes, etc.) due to ultraviolet rays, eye discomfort, conjunctivitis, lumps, swelling eyes, foreign body feeling, etc. It can be used for the purpose of prevention and improvement, as well as for the purpose of corneal protection, corneal repair, antiallergic, antibacterial, UV care, eye disease prevention, dry eye countermeasures, eyelid friction lubrication, tear oil layer replenishment, and the like.

The oil-based eye drops of the present invention are filled in a container made of polyethylene terephthalate or polypropylene.

The container may be made of polyethylene terephthalate or polypropylene, and the inside of the container to which the oil-based eye drops touch may be made of polyethylene terephthalate or polypropylene, at least at least during use and storage of the oil-based eye drops of the present invention. The material of the container is not limited. The container is not limited to this limitation, that is, the inside of the container to which the oil-based eye drops come into contact may be provided with both polyethylene terephthalate and polypropylene. In the present invention, as the container, a conventionally known container for eye drops can be used as long as this is the case.

Further, the container may be colored or colorless as long as it has transparency to such an extent that there is no problem in observing foreign substances.

In the present invention, the container is more preferably colored such as orange from the viewpoint of improving the photostability of vitamin A. This makes it possible to further improve the photostability of vitamin A, especially under light irradiation. The colored color such as orange means that the light transmittance at a wavelength of 600 nm is preferably 60% or less, more preferably 50% or less, although it is not particularly limited. At least a part of the colorless and transparent container may be wrapped in a colored film such as orange. Such colored containers are known, and conventionally known containers may be used in the present invention. When the container used in the present invention is transparent or has a high light transmittance at a wavelength of 600 nm, it is preferable that the container containing the oil-based eye drops be stored under light shielding. The light transmittance at a wavelength of 600 nm is measured using a spectrophotometer.

Further, the capacity of the container is not limited, but preferably 3 to 20 mL is exemplified, and more preferably 5 to 15 mL is exemplified.

In the present invention, as far as this is concerned, the container may preferably follow the description of the eye drops in the general rules of the pharmaceutical product in the 16th revised Japanese Pharmacopoeia.

The number of times and the amount of the oil-based eye drop of the present invention are not limited, and usually 1 to several times a day, preferably 3 to 6 times a day, more preferably 3 to 4 times a day are exemplified, and usually. An example is 1 to several drops at a time, preferably 1 to 3 drops at a time, and more preferably 1 to 2 drops at a time. Further, the oil-based eye drop of the present invention is not limited as long as it is used by dropping it into the eyes, but it is preferable to keep the eyes closed for 10 to 60 seconds, more preferably 40 to 60 seconds after the dropping. Is mentioned as.

According to the present invention, an oily eye drop containing castor oil, at least one selected from the group consisting of vitamins A and E, and 0 to 8% by mass of water is made of polyethylene terephthalate or polypropylene. By filling the container in the above, the residual ratio of vitamins A and E in the oil-based eye drops can be increased. Since vitamins A and E are often added to eye drops as one of the active ingredients, it is very important to increase the residual ratio of these.

From this, the present invention is preferably filled in a container made of polyethylene terephthalate or polypropylene, castor oil, at least one selected from the group consisting of vitamins A and E, and 0 to 0 to water. It can be said that an oil-based eye drop containing 8% by mass is provided.

Further, according to the present invention, as shown in Examples described later, by further combining l-menthol with the oily eye drops containing castor oil, castor oil is particularly contained even though it contains castor oil. The viscosity of the oil-based eye drops can be reduced even when the oil-based eye drops are contained in a high content. In studying the present invention, the present inventor of an eye drop containing a large amount of castor oil, due to the viscosity of castor oil, the amount of one drop increases when dropped from a container, and the amount of one drop increases from the eye when used. I noticed that there was a problem such as lowering. According to the present invention, by further combining l-menthol with the oil-based eye drops containing castor oil, the amount of one drop of the oil-based eye drops can be further reduced, and excess eye drops overflow from the eye during use. It is possible to suppress problems such as a decrease in usability.

Further, according to the present invention, according to the present invention, it is possible to suppress the adhesion of the oil-based eye drops to the wall surface inside the container, and in particular, the oil-based eye drops are contained in the container in the late stage of use when the remaining amount in the container is low. It is possible to reduce the stress of the user, such as the oil-based eye drops that adhere to the wall surface and are difficult or impossible to drip.

In addition, the present inventor has noticed that it is difficult to tell that oil droplets have entered the eyes even when castor oil alone is instilled, and there is a problem that the oil droplets are instilled too much and overflow from the eyes. According to the present invention, by using l-menthol in combination, it becomes easy to understand that castor oil is instilled due to the refreshing feeling, and the feeling of use can be further improved.

In addition, it is known that sunflower oil has skin sensitization, and it has been reported that contact with sunflower oil causes allergic contact dermatitis such as swelling and itching (Kunihiko Yoshikawa et al., Sunflower oil). A case of contact dermatitis, skin, Vol. 28, special issue No. 2, August 1986, increase 263- increase 265). In studying the present invention, the present inventor has found that the skin sensitivities of castor oil can be suppressed by using castor oil in combination with vitamin A, as shown in Examples described later. As described above, according to the present invention, the skin sensitization of castor oil can be suppressed by using castor oil in combination with vitamin A. In particular, by using castor oil in combination with both vitamins A and E, the skin sensitization of castor oil can be suppressed. In the present invention, skin sensitization is evaluated according to the peptide bondability test shown in Examples described later.

For this reason, the present invention also comprises an oily eye drop containing castor oil, at least one selected from the group consisting of vitamins A and E, and 0 to 8% by mass of water, made of polyethylene terephthalate. Alternatively, it can be said to provide a method for reducing and suppressing the residual ratio of at least one selected from the group consisting of vitamins A and E in the oily eye drops, which is characterized by filling in a container made of polypropylene. Castor oil, vitamin A, vitamin E, oily eye drops, residual vitamin A, etc. used in the method, components that can be used for oily eye drops, the content of each component, etc. are as described above. It will be explained in the same way.

From this, it can be said that the present invention also provides a method for reducing the viscosity of the oil-based eye drops, which is characterized by further combining l-menthol with the oil-based eye drops. Castor oil, oil-based eye drops, l-menthol and the like used in the method, components that can be used in the oil-based eye drops, the content of each component and the like are also described in the same manner as described above.

From this, it can be said that the present invention also provides a method for suppressing skin sensitization of castor oil, which is characterized by combining castor oil and vitamin A in the oil-based eye drops. It can also be said that the present invention provides a method for suppressing skin sensitization of castor oil, which comprises combining castor oil, vitamins A and vitamin E in the oily eye drops. Castor oil, vitamins A, vitamin E, oily eye drops, components that can be used in the oily eye drops, the content of each component, and the like used in these methods are also described in the same manner as described above.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

Test Example 1
According to Table 1 below, each component was mixed to prepare an oil-based eye drop (Examples 1 to 5, Comparative Example 1). In the oil-based eye drop containing water and polysorbate 80, water and polysorbate 80 were mixed while heating, and the obtained mixture and the remaining components were mixed to prepare an oil-based eye drop.

3 mL of the obtained oil-based eye drops was filled in a container for eye drops and stored at 50 ° C. in the dark for 7 days. The containers for eye drops used are as follows.
PP container: TSE-5mL (PP) (Taisei Kako Co., Ltd., polypropylene)
PET container: SG-PET 10mL container primary color (manufactured by Shinko Chemical Co., Ltd., made of polyethylene terephthalate)
PE container: TSE-5mL (PE) (made by Taisei Kako Co., Ltd., made of polyethylene)
The concentrations of retinyl palmitate and tocopherol acetate contained in the oily eye drops before and after storage were measured by HPLC (high performance liquid chromatography) according to a conventional method, and the ratio of the concentration after storage to the concentration before storage was measured. , Residual%, respectively.

The results are shown in Table 1.

As is clear from Table 1, compared with the case where the PE container is filled with the oil-based eye drops (Comparative Example 1), when the PP container or the PET container is filled with the oil-based eye drops (Examples 1 to 1). 5) The residual rates of retinol palmitate and tocopherol acetate were improved. It was also confirmed that when the oil-based eye drops contain dibutylhydroxytoluene, the residual rates of retinol palmitate and tocopherol acetate are further improved, and in particular, the residual rate of tocopherol acetate is further increased.

Further, although not shown in Table 1, in Comparative Example 1, an LDPE container (SK5 eye container, Taisei Kako Co., Ltd., low density polyethylene) was filled with an oil-based eye drop instead of the PE container. However, the residual rates of retinol palmitate and tocopherol acetate in Examples 1 to 5 were both high.

For this reason, by filling a PP container or a PET container with an oil-based eye drop containing castor oil and vitamins A and E, stability at high temperatures can be improved, and vitamin As can be improved. It was found that the residual rate of vitamin E and vitamin E in oil-based eye drops can be improved.

Test Example 2
According to Table 2 below, each component was mixed to prepare an oil-based eye drop (Examples 6 to 10). In an oil-based eye drop containing water and polysorbate 80 or polyoxyethylene (POE) hardened castor oil 60, these components are mixed while being heated, and the obtained mixture and the remaining components are mixed. , An oily eye drop was prepared.

The viscosity of the obtained oil-based eye drops was measured according to the following procedure.

Spindle F was used in the Brookfield Viscometer (LVDV-II +) (manufactured by Brookfield Engineering Labs), and the screw tube No. 7 (35 × 78, manufactured by Maruel Co., Ltd.) was filled with 50 g of the obtained oil-based eye drops, and the viscosity was measured 5 minutes after the start of measurement. The measurement was performed at a rotation speed of 4 rpm and room temperature (24 ° C.). The results are shown in Table 2.

As is clear from Table 2, the oil-based eye drops containing l-menthol (Examples 6 to 9) are compared with the oil-based eye drops containing no l-menthol (Example 10). Was able to further reduce the viscosity of.

From this, it was found that the viscosity of the oil-based eye drops can be further reduced by further combining l-menthol with the oil-based eye drops.

Further, in the oil-based eye drops containing l-menthol, it became easy to understand that the eye drops were instilled due to the refreshing feeling of l-menthol.

Further, when the stability of the oil-soluble eye drops of Examples 6 to 10 at high temperatures was evaluated in the same manner as in Test Example 1, when these oil-soluble eye drops were filled in a PP container or a PET container, respectively. It was found that the stability at high temperature can be improved.

From this, it was found that by further combining l-menthol with the oil-based eye drops, the viscosity of the oil-based eye drops can be further reduced in addition to the improvement of the stability of the oil-based eye drops.

Test Example 3
3 mL of the oil-based eye drops of Examples 6 and 10 obtained as described above were filled in a container for eye drops of TSE-5 mL (PP) (manufactured by Taisei Kako Co., Ltd., made of polypropylene), and oil-based eye drops were applied from the container. The agent was dropped, the weight of one drop was measured with an electronic balance, and the average value of three times was calculated.

The results are shown in Table 3.

As is clear from Table 3, the weight of one drop in Example 6 was 0.021 mg, which was less than the weight of one drop in Example 10 of 0.029 mg.

From the results of the above test example and this test example, by further combining l-menthol with the oil-based eye drop, in addition to improving the stability of the oil-based eye drop, the viscosity of the oil-based eye drop can be reduced, and one drop can be dropped. It turned out that the amount could be reduced.

Test Example 4
The oil-based eye drops of Example 6 obtained as described above were filled in the following two types of eye drop containers, and used with a photostability test device LT-120A (2900 lpx manufactured by Nagano Science Co., Ltd.). It was stored for 13 days under light irradiation.
Example 6A: TSE-5mL (PP) orange (manufactured by Taisei Kako Co., Ltd., made of polypropylene, light transmittance at a wavelength of 600 nm: 45% or less)
Example 6B: PP container for eye drops used in Test Example 1, colorless (transparent)
The concentrations of retinyl palmitate and tocopherol acetate contained in the oil-based eye drops before and after storage were measured in the same manner as in Test Example 1, and the ratio of the concentration after storage to the concentration before storage was defined as% residual. Calculated. The results are shown in Table 4.

As is clear from Table 4, in Example 6A using the orange container under light irradiation, the residual rate of retinol palmitate was as high as in Test Example 1, whereas it was light irradiation. In Example 6B using a colorless (transparent) container below, the residual rate was 0%. For this reason, the oil-based eye drops shown in the above-mentioned examples are stored in a PP container or a PET container, and are stored under some light-shielding condition, such as being stored by blocking light or being filled in a colored container. Was found to be preferable.

Test Example 5
According to Table 5 below, each component was mixed to prepare an oil-based eye drop (Examples 10 to 15). Similar to Test Example 1, in the oil-based eye drop containing water and polysorbate 80, water and polysorbate 80 are mixed while heating, and the obtained mixture and the remaining components are mixed to obtain an oil-based eye drop. Prepared. An oil-based eye drop containing only castor oil was used as Reference Example 1.

The obtained Examples 10 to 15 and Reference Example 1 were evaluated for skin sensitization by a peptide bond test. The peptide bond test is one of the skin sensitization tests, and is an evaluation method based on the binding between hapten and protein, which is a reaction in the early stage of establishment of skin sensitization. It can be judged that the higher the binding rate, the higher the risk of skin sensitization. The test procedure was as follows.

The oil-based eye drops of Examples 10 to 15 and Reference Example 1 obtained as described above were mixed with DMSO (dimethyl sulfoxide) so as to be 100 mg / 1 mL to obtain a test solution. Two samples (sample, control) were prepared for each test solution using a vial light-shielding bottle for HPLC (High Performance Liquid Chromatograph).
Sample test solution: Cysteine-containing peptide = 1: 1
Control DMSO: Cysteine-containing peptide = 1: 1
Here, as the cysteine-containing peptide, a synthetic peptide having the sequence of "H-Phe-Thr-Leu-Cyc-Phe-Arg-NH ₂ " was used.

After preparing these samples, they were allowed to stand at 40 ° C. for 24 hours under shading. Then, for each sample, the amount of unreacted cysteine-containing peptide (peak area) was analyzed by HPLC under the following conditions.
Column: ODS column 4.6 mm x 150 mm
Temperature: 40 ° C
UV detection wavelength: 220nm
Moving layer / flow rate: A 0.1% aqueous phosphoric acid solution and 0.1% acetonitrile acetonitrile were mixed and equilibrated, and then the flow rate was adjusted so that the peak of the cysteine-containing peptide was 13 minutes.

From the peak areas of the sample and the control thus obtained, the peptide bond rate was calculated by the following formula.
Peptide bond rate = (1- (sample peak area / control peak area)) x 100
The results are shown in Table 5.

As is clear from Table 5, in Reference Example 1 containing only castor oil, the binding rate was as high as 5.29%. Further, also in Examples 14 and 15 in which castor oil and tocopherol acetate were combined, the binding ratio was 5.59% and 5.18%, which were the same results as in Reference Example 1. On the other hand, in Examples 10 to 13 in which castor oil and retinol palmitate were combined, the binding rate was 1.92% at the highest.

From this, it was found that by combining castor oil and vitamin A, the peptide bond rate was lower than that of castor oil alone, and the risk of skin sensitization was reduced.

Further, in Examples 10 and 13 in which the castor oil was combined with vitamins A and E, the peptide bond rate could be further reduced as compared with Examples 11 and 12 in which only the vitamin A was combined with castor oil.

From this, it was found that by combining castor oil with vitamin A and further with vitamin E, the risk of skin sensitization can be reduced in addition to improving the stability of oil-based eye drops. ..

Formulation Examples Oil-based eye drops were prepared according to the formulation shown in Table 6 and filled in PET or PP containers (orange, light transmittance at a wavelength of 600 nm: 50% or less). Formulation Examples 1 to 13 were prepared by mixing the components (A) and (B) and filled in a container. Formulation Examples 14 to 16 are prepared by warming the mixed solution obtained by mixing the component (B) to 80 ° C. and gradually adding the mixed solution obtained by separately mixing the component (A) while stirring. , Filled in a container. These are oil-based eye drops that can retain vitamin A and / or vitamin E in a higher proportion and can be expected to have high stability, as in the case of the above test example.

Claims (3)

Oil-based eye drops filled in a container made of polyethylene terephthalate or polypropylene, wherein the oil-based eye drops are castor oil, at least one selected from the group consisting of vitamins A and E, and l-menthol . And 0 to 8% by mass of water. The oil-based eye drop according to claim 1 , wherein the oil-based eye drop further contains dibutylhydroxytoluene. The oil-based eye drop according to claim 1 or 2 , wherein the color of the container is orange.