Liquid container and applicator

Abstract

Provided is a liquid agent container for filling with a liquid agent containing efinaconazole, which has both of two mutually contradictory properties: capable of maintaining light stability and capable of visually confirming the amount of the liquid agent from the outside. A liquid agent container capable of filling with a liquid agent containing 10% efinaconazole, which is a container formed of a synthetic resin containing titanium dioxide (IV), has a light transmittance of 0.20% or less in the wavelength range of 200 to 360 nm, and has a light transmittance of 0.25% or more at a wavelength of 700 nm, and is capable of visually confirming the amount of the liquid agent filled in the liquid agent container from the outside.

Description

Technical Field

[0001] This invention relates to a liquid container for filling a liquid containing icoconazole. Furthermore, this invention also relates to an applicator having the liquid container. Background Technology

[0002] Ifluconazole is a triazole compound with antifungal activity, represented by the following formula (I): .

[0003] Efluconazole is well known as the active ingredient in topical onychomycosis treatments. Liquid formulations containing evaconazole are sold in Japan under the pharmaceutical name Clenafin (registered trademark) 10% Topical Nail Solution, and in the United States under the pharmaceutical name JUBLIA (registered trademark) 10% Topical Solution (Non-Patent Literature 1).

[0004] An increase in ieconazole analogues was observed in photostability stress tests of liquid formulations containing ieconazole. Therefore, using containers where the remaining amount of liquid can be easily visually confirmed (e.g., colorless, transparent glass containers) will promote the decomposition of ieconazole. Thus, ensuring the stability of the formulation under light exposure is extremely important. For this reason, conventional ieconazole formulations have been filled in white, opaque, light-proof containers. However, detailed understanding of the photostability of ieconazole remains unclear.

[0005] Treatment for onychomycosis is often lengthy, sometimes lasting several months when using liquid medications containing iefluconazole. Patients are advised to return for a follow-up appointment before the medication runs out. Therefore, visually confirming the remaining amount of medication is crucial for improving patient adherence. However, conventional iefluconazole formulations are typically packaged in opaque, light-proof containers, making it difficult to visually assess the amount of medication remaining.

[0006] Ifluconazole is used as a topical liquid for application to the nails. Therefore, it is preferable to use an applicator that integrates a liquid container for filling the medication with a brush-like component for application to the nails. For example, Patent Document 1 discloses an applicator for applying onychomycosis medication to the affected area as such a brush-like application container. As an example of the liquid container (i.e., the bottle body) constituting such an applicator, a liquid container formed of an organic material and capable of holding the liquid medication is disclosed. Examples of organic materials include polyolefins such as polyethylene and polypropylene, and aromatic polyesters such as polyethylene terephthalate and polybutylene terephthalate.

[0007] However, the document makes no mention of aniconazole, nor does it disclose a liquid container that can be filled and stably held for aniconazole.

[0008] To date, various medical containers have been proposed that allow for visual confirmation of liquid dosage from the outside and prevent the active ingredients from deteriorating due to light.

[0009] Patent document 2 discloses an ultraviolet-blocking medical container made of a plastic in which 0.01 to 1.00% by weight of titanium dioxide with an average particle size of 10 to 40 μm is added to a thermoplastic resin.

[0010] Patent document 3 discloses a pharmaceutical preparation packaged in a transparent container, which contains a pharmaceutical preparation containing tranilast or its salt and is packaged in a transparent container that has been treated to block light of wavelengths of 350 to 450 nm.

[0011] Patent document 4 discloses a container using a colored transparent resin containing a colorant, which has a transmittance of less than 10% for light with a wavelength of 200nm to 500nm and a transmittance of more than 80% for light with a wavelength of 540nm to 800nm.

[0012] However, the containers described in Patent Documents 2-4 are not applicators for applying liquid nail polish. Furthermore, even with the container described in Patent Document 2, the contents may deteriorate according to that document. The containers described in Patent Documents 3 and 4 also fail to completely block ultraviolet light.

[0013] Existing technical documents Patent documents Patent Document 1: International Publication No. 2013 / 005434 Patent Document 2: Japanese Patent Application Publication No. 8-98870 Patent Document 3: Japanese Patent Application Publication No. 2014-015467 Patent Document 4: Japanese Patent Application Publication No. 2007-061192 Non-patent literature Non-patent literature 1: Clenafin (registered trademark) 10% Nail Spray Pharmaceutical IF document, revised July 2022 (8th edition) Summary of the Invention

[0014] The problem that the invention aims to solve One of the problems to be solved by the present invention is to provide a liquid container for filling icoconazole solution, which has two contradictory characteristics: it can maintain photostability and the amount of liquid can be visually confirmed from the outside.

[0015] Another problem to be solved by the present invention is to provide a brush-brush applicator (in other words, an applicator) for filling and applying effluconazole liquid, which, while maintaining photostability, allows for visual confirmation of the amount of liquid from the outside and enables the application of an appropriate amount of liquid.

[0016] Methods for solving problems To address the aforementioned issues, the inventors conducted a detailed study on the photostability of iefluconazole. The results showed that iefluconazole is highly susceptible to ultraviolet (UV) light, exhibiting yellowing and / or an increase in similar substances over time. Furthermore, it was clarified that even if the container's UV transmittance is, for example, only about 1%, it still promotes the decomposition of iefluconazole.

[0017] As mentioned above, various liquid containers have been proposed to date that can both suppress the transmission of ultraviolet light and allow for confirmation of the remaining amount of contents. However, none of these are suitable liquid containers or applicators for applying liquids to fingernails. Furthermore, given that iefluconazole is highly susceptible to ultraviolet light, the existing containers cannot be used as containers for iefluconazole formulations.

[0018] After research, the inventors discovered that by precisely controlling the light transmittance of the container in both the ultraviolet and visible light regions, it is possible to create a container that simultaneously possesses two contradictory properties: maintaining the photostability of icoconazole while allowing visual confirmation of the liquid from the outside.

[0019] Specifically, it was found that the photostability of iefluconazole can be maintained by using a container with the transmittance of ultraviolet light controlled within the range of 0% to 0.20%. Furthermore, the inventors also discovered that, in order to visually confirm the remaining amount of the liquid, the transmittance of a specific wavelength of light in the visible light region needs to reach 0.25% or higher.

[0020] Based on the above understanding, the inventors conducted more detailed research in order to discover a container suitable for filling liquids containing ciproconazole.

[0021] As mentioned earlier, an applicator has been proposed as a container for onychomycosis treatment agents. This applicator has a generally cylindrical container with an opening, and a columnar brush member formed by integrating synthetic fiber bundles into a columnar shape is provided at the opening (Patent Document 1). This brush member functions as an application component, allowing the user to invert the container to allow the liquid to penetrate the brush member and apply the liquid to the nail. However, when the container is inverted for use, depending on the usage environment and container design, excessive or insufficient liquid may be dispensed. Therefore, this may hinder the smooth application of the liquid.

[0022] Therefore, to achieve a good user experience with a brush-type nail polish applicator, the container material, hardness, and / or thickness must be appropriately designed to ensure that the appropriate amount of liquid can be quickly dispensed from the container during actual use. On the other hand, since the thickness of the container also affects light transmittance, designing a container that balances and addresses multiple issues such as light stability and visibility is extremely difficult.

[0023] In view of the above problems, after further in-depth research, the inventors discovered that an excellent container can be obtained that can comprehensively solve multiple problems such as light stability, visibility, and the user experience of a brush-like applicator.

[0024] Based on the above research results, according to one embodiment of the present invention, a liquid container suitable for use as an applicator for applying liquid to nails can be provided. Furthermore, according to another embodiment of the present invention, an applicator can also be provided, which has a columnar bristle member formed by integrating synthetic fiber bundles into a columnar shape at the opening of the liquid container. The applicator equipped with the liquid container of one embodiment of the present invention, when inverted in actual use, can quickly and appropriately dispense liquid, thus providing an excellent user experience.

[0025] Furthermore, according to one embodiment of the applicator, the number of drops required for the liquid to stop dripping within 1 minute when 4 mL of 10% ethanol solution of 10% fluoroconazole is filled into the applicator and it is inverted at 32°C is 7 to 10.

[0026] In summary, the inventors have researched liquid containers suitable for filling effluconazole solution. The result is a container that ensures the photostability of the active ingredient, allows for visual confirmation of the remaining liquid volume, and provides an excellent user experience, thus completing this invention.

[0027] That is, the present invention is as follows.

[0028] [1] A liquid container that can be filled with 10% effluconazole solution, wherein, Liquid containers are formed from synthetic resins containing titanium dioxide (IV). Its light transmittance in the wavelength range of 200-360nm is less than 0.20%, and its light transmittance in the wavelength range of 700nm is more than 0.25%. The amount of liquid in the liquid container can be visually confirmed from the outside.

[0029] [2] The liquid container according to [1] is characterized in that the liquid container is a generally cylindrical polyethylene container with an opening at the top, is a container consisting of a single layer of at least titanium dioxide (IV) uniformly dispersed in polyethylene, and is a non-flexible rigid container.

[0030] [3] The liquid container according to [1] or [2], wherein the internal volume of the liquid container is 8 to 12 mL and the sidewall thickness of the liquid container is 0.8 to 1.0 mm.

[0031] [4] The liquid container according to any one of [1] to [3] is characterized in that it contains 0.09 to 0.33 parts by weight of titanium dioxide (IV) relative to 100 parts by weight of synthetic resin.

[0032] [5] The container according to any one of [1] to [4] is characterized in that it contains 0.10 to 0.30 parts by weight of titanium dioxide (IV) relative to 100 parts by weight of synthetic resin.

[0033] [6] The liquid container according to any one of [1] to [5] is characterized in that it contains 0.18 to 0.22 parts by weight of titanium dioxide (IV) relative to 100 parts by weight of synthetic resin.

[0034] [7] The liquid container according to any one of [1] to [6] is characterized in that it does not contain any coloring components other than titanium dioxide (IV).

[0035] [8] A liquid container according to any one of [1] to [6], wherein the light transmittance in the liquid container in the wavelength range of 700 to 780 nm is 0.25% or more.

[0036] [9] The liquid container according to any one of [1] to [8], wherein the light transmittance in the liquid container in the wavelength range of 700 to 780 nm is 0.40% or more.

[0037]

[10] The liquid container according to any one of [1] to [9], wherein the light transmittance in the liquid container in the wavelength range of 200 to 360 nm is 0.10% or less.

[0038]

[11] The liquid container according to any one of [1] to

[10] is packaged with a film that is not ultraviolet-absorbing.

[0039]

[12] An applicator comprising: Liquid containers as described in any one of [1] to

[11] ; Synthetic fiber bundles are integrated into columnar brush bristle components; and A bottomed cylindrical retainer located between the liquid container and the cylindrical brush component, having a cylindrical body and a bottom. The bottomed cylindrical retainer fits liquid-tightly into the opening of the liquid container. The bottom of the bottomed cylindrical retainer has at least one fine hole. The columnar bristle component is inserted into the cylindrical body with a bottom cylindrical retainer. The liquid can flow from the liquid container to the columnar bristle component through fine holes. Thus, when the liquid container is inverted during use, the liquid will penetrate into the columnar bristle component and can be applied to the user's nails.

[0040]

[13] According to the applicator of

[12] , the columnar bristle component is formed by bundling synthetic fibers with a fiber diameter in the range of 7 to 50 μm at a density in the range of 0.25 to 0.50. The bottomed cylindrical retainer has a circular orifice with a diameter of 0.9 to 1.3 mm.

[0041]

[14] The applicator according to

[12] or

[13] is characterized in that, when the applicator filled with 4 mL of liquid is inverted at 32°C, the number of drops required to stop dripping within 1 minute is 7 to 10 drops.

[0042]

[15] A method for photostabilizing icoconazole, comprising the step of filling a liquid container containing 10% icoconazole solution into a liquid container as described in any one of [1] to

[11] or an applicator as described in any one of

[12] to

[14] .

[0043] The effects of the invention By using the liquid container according to one embodiment of the present invention, the photodegradation of iefluconazole can be suppressed, thereby enabling long-term stable storage of the iefluconazole liquid. Furthermore, the user can visually confirm the remaining amount of liquid in the container from the outside. In addition, by providing a columnar brush member made of synthetic fiber bundles integrated into the opening of the liquid container with the above-described features, an applicator can be constructed. This applicator, when inverted in actual use, can quickly dissipate the liquid, and the amount of liquid dripping is moderate, thus providing a good user experience. Attached Figure Description

[0044] Figure 1 This is a schematic front view illustrating an example of an applicator with a liquid container according to an embodiment of the present invention.

[0045] Figure 2 It has a cap that covers the columnar bristle component. Figure 1 A schematic cross-sectional view of the applicator shown.

[0046] Figure 2A It is used for explanation Figure 1 The diagram shows a schematic cross-sectional view of the liquid container.

[0047] Figure 2B It is used for explanation Figure 1 A schematic perspective view of the columnar brush component shown.

[0048] Figure 2C It is used for explanation Figure 1 The figure shows a schematic cross-sectional view of a bottomed cylindrical retainer.

[0049] Figure 3 The light transmittance spectrum of the container in Comparative Example 1 in the wavelength range of 200 nm to 800 nm is shown.

[0050] Figure 4 It is Figure 3 The image after magnification of the vertical axis.

[0051] Figure 5 The light transmittance spectrum of the container in Comparative Example 2 is in the wavelength range of 200 nm to 800 nm.

[0052] Figure 6 The light transmittance spectrum of the container in Comparative Example 3 is in the wavelength range of 200 nm to 800 nm.

[0053] Figure 7 The light transmittance spectrum of the container in Comparative Example 4 is in the wavelength range of 200 nm to 800 nm.

[0054] Figure 8 It is the light transmittance spectrum of the container in the wavelength range of 200nm to 800nm ​​of Example 1.

[0055] Figure 9 It is Figure 8 The image after magnification of the vertical axis.

[0056] Figure 10 The light transmittance spectrum of the container in Example 2 is in the wavelength range of 200nm to 800nm.

[0057] Figure 11 It is Figure 10 The image after magnification of the vertical axis.

[0058] Figure 12 It is the light transmittance spectrum of the container in the wavelength range of 200nm to 800nm ​​of Example 3.

[0059] Figure 13 It is the light transmittance spectrum of the container in the wavelength range of 200nm to 800nm ​​of Example 4.

[0060] Figure 14 The light transmittance spectrum of the container in Example 5 is in the wavelength range of 200nm to 800nm. Detailed Implementation

[0061] The following explains the various terms used in this specification. Additionally, when "~" is used in this specification to indicate a numerical range, the values ​​at both ends are included.

[0062] In this specification, "ultraviolet region" refers to light in the wavelength range of 200nm to 360nm, and "visible light region" refers to light in the wavelength range of 400nm to 780nm.

[0063] <1> Container In this specification, liquid containers are sometimes simply referred to as "containers". In addition, liquid containers equipped with columnar brush parts are sometimes referred to as "brush-equipped applicator" or "applicator".

[0064] One embodiment of the present invention is as follows: Figure 1 and Figure 2 As shown. Figure 1 This is a schematic front view of an example of an applicator with a liquid container according to one embodiment of the present invention. Figure 2 For a cap having a cover for columnar bristle components, Figure 1 A schematic cross-sectional view of the applicator shown. Figure 1 As shown, the applicator 100 of one embodiment of the present invention may be an applicator having a generally cylindrical liquid container 1 capable of being filled with a liquid medicine, a bottomed cylindrical retainer 2, and a cylindrical bristle component 3. Furthermore, as... Figure 2 As shown, the applicator 100 may also have a removable cap 4 to cover the brush part 3.

[0065] Figure 2A A schematic cross-sectional view of the liquid container 1 is shown separately. The liquid container 1 includes a liquid container body 11 and a liquid container neck 12. In the illustrated example, the liquid container body 11 is generally cylindrical, and its upper part is continuously formed with the liquid container neck 12 by a curved surface. The liquid container neck 12 is provided with an opening 14, and the columnar bristle member 3 is mounted to the opening 14 via a bottomed cylindrical retainer 2 (see...). Figure 2 The outer surface of the neck 12 of the liquid container is provided with a thread 15 that can be threadedly connected to the cap 4.

[0066] The liquid container body 11 has a side wall 11a and a bottom wall 11b extending circumferentially along the generally cylindrical liquid container body 11. The side wall 11a and the bottom wall 11b together define a filling space S for filling with liquid. When the applicator is not in use or is stored, it is placed with the outer surface of the bottom wall 11b in contact with a flat surface such as a table. The side wall 11a is held by the user when using the applicator 100.

[0067] Figure 2BThis is a schematic perspective view illustrating the columnar bristle component 3. The columnar bristle component 3 is a columnar bristle component formed by integrating synthetic fiber bundles into a columnar shape. The columnar bristle component 3 includes a columnar bristle component body 31, a columnar bristle component neck 32, and a columnar bristle component front end 33. The outer surfaces of the columnar bristle component body 31 and the columnar bristle component neck 32 are cured with an adhesive, integrating the synthetic fibers composed of fine polyester contained inside the columnar bristle component 3. The columnar bristle component front end 33 is formed into a bristle shape by loosening the synthetic fiber bundles fixed by the adhesive at the front end of the columnar bristle component neck 32. Inside the columnar bristle component body 31 and the columnar bristle component neck 32, there are gaps between the synthetic fibers for liquid agents to pass through, thus forming a structure in which, when the end face of the columnar bristle component body 31 is immersed in a liquid agent, the liquid agent seeps out from the other end of the synthetic fibers through capillary action.

[0068] Figure 2C This is a schematic cross-sectional view illustrating the bottomed cylindrical retainer 2. The bottomed cylindrical retainer 2 includes a bottomed cylindrical retainer body 21 and an annular flange portion 22. The bottomed cylindrical retainer body 21 has a cylindrical shape. This cylindrical shape can be appropriately adjusted according to the outer peripheral shape of the columnar bristle component 3 so that the columnar bristle component 3 can be inserted. Figure 2C As shown, the bottomed cylindrical retainer 2 has a bottom 23, which is seamlessly joined to the cylindrical bottomed cylindrical retainer body 21. A fine hole 24 is provided at the center of the bottom 23. Through this fine hole 24, a structure is formed in which liquid medicine contained inside the liquid container 1 can move into the interior of the bottomed cylindrical retainer 2. Figure 2C In the middle, 35 is a support member formed on the inner surface of the bottomed cylindrical retainer body 21 for supporting the columnar brush member 3.

[0069] However, the specific shapes of the components of the applicator 100 according to one embodiment of the present invention are not limited to the illustrated form.

[0070] In one embodiment of the present invention, the applicator is inverted during use. At this time, one end of the bristle member receives the liquid from the liquid container, and the liquid penetrates within the bristle member through capillary action. The other end of the bristle member functions as an applicator for applying the liquid to the nail. Thus, the liquid is supplied to the nail via the bristle member located at the opening of the liquid container.

[0071] By inverting the applicator (i.e., liquid container) according to one embodiment of the present invention, the user can allow the liquid to quickly penetrate from the opening of the liquid container into the bristle component and smoothly apply an appropriate amount of liquid to the nail. Therefore, the applicator and liquid container according to one embodiment of the present invention provide a better user experience.

[0072] In one embodiment of the invention, the liquid container can be any form of container, as long as it can be filled with liquid without leakage, but preferably, for example, as shown in the figure. Figure 2A The container shown is roughly cylindrical with an opening at the top.

[0073] The main material of the liquid container in one embodiment of the present invention is any synthetic resin suitable for filling the agent inside, and there are no particular restrictions. However, as the base resin, polyethylene terephthalate, polybutylene terephthalate, polyethylene, polystyrene, polypropylene or polyvinyl chloride are preferred, and polyethylene is particularly preferred.

[0074] In one embodiment of the invention, the liquid container is not elastically deformable under normal use conditions; that is, it is a rigid synthetic resin container that is neither elastic nor flexible. The rigid synthetic resin container eliminates the need for the user to adjust the liquid dispensing rate by gripping it. The liquid passively diffuses within the bristle component via capillary action. Therefore, the dispensing rate is less likely to differ between different users, making it a preferred container from this perspective.

[0075] In one embodiment of the present invention, the internal volume of the liquid container is not particularly limited, but is preferably 8 to 12 mL.

[0076] In one embodiment of the present invention, the thickness of the sidewall of the liquid container is not particularly limited, but is preferably 0.8 mm to 1.0 mm in order to comprehensively solve the problems of the present invention.

[0077] In this specification, "light blocking" means using substances that scatter or absorb light to prevent it from passing through.

[0078] In this invention, there are no particular limitations on the specific method of blocking ultraviolet light. A substance capable of blocking ultraviolet light within the specified wavelength range described later can be used, for example, in the following manner.

[0079] a) A method of adding a substance that blocks ultraviolet light to a synthetic resin used for containers (e.g., adding an ultraviolet blocking substance such as titanium dioxide to a base resin and then molding it into a container shape).

[0080] b) A method of separately installing a component containing a UV-blocking material (e.g., a film) on the surface of the container (e.g., installing a shrink film containing a UV-scattering agent onto the container).

[0081] c) Applying a UV-blocking substance to the surface of the container.

[0082] Of the methods described above, b) and c) are uneconomical due to the increased number of manufacturing steps and components. On the other hand, a) is preferred due to its simple manufacturing process, but it is not easy to achieve both UV blocking and visibility assurance. Furthermore, if an appropriate container material is not selected, there is a possibility that components of the container material may leach into the liquid inside.

[0083] In one embodiment of the present invention, a preferred liquid container is formed by adding an ultraviolet-blocking substance to the synthetic resin used in the container to block ultraviolet radiation. Therefore, in one embodiment of the present invention, a preferred liquid container is a single-layer container in which the ultraviolet-blocking substance is uniformly dispersed in the main component of the container material.

[0084] Here, "ultraviolet blocking material" refers to a material capable of blocking ultraviolet rays, preferably titanium dioxide (IV). In other words, "a container consisting of a single layer in which ultraviolet blocking material is uniformly dispersed in the main component of the container material" refers to a container formed by uniformly dispersing coloring components such as titanium dioxide (IV) in a base resin.

[0085] In one embodiment of the invention, a preferred liquid container is constructed of a single thermoplastic synthetic resin layer, rather than multiple layers. Furthermore, the container does not have areas on its sides that are free of UV-blocking materials (or areas with a lower concentration of UV-blocking materials compared to other parts). While such areas could function as windows or scales for visually confirming the volume, a preferred container in one embodiment of the invention does not have such windows or scales.

[0086] In one embodiment of the present invention, for a preferred liquid container, since the material components used for the liquid container are uniformly dispersed among themselves, it can be formed in a single molding process. Therefore, the liquid container of one embodiment of the present invention can be manufactured by a simple and low-cost manufacturing method.

[0087] In one embodiment of the invention, a preferred liquid container is characterized by being a synthetic resin container not packaged with a UV-absorbing film. Examples of UV absorbers that can be used in this film include salicylic acid derivatives, benzophenone derivatives, triazine derivatives, benzotriazole derivatives, and cyanoacrylate derivatives. The UV-absorbing film may contain, for example, a shrinkable PET resin as a base material. By shrinking such a UV-absorbing film to cover the surface of the liquid container, the same effect as a synthetic resin container doped with a UV blocker can be obtained.

[0088] However, when using UV-absorbing films, partial or complete damage may occur due to user error or intentional acts, resulting in unintended effects on the photostability of the contents. Furthermore, using UV-absorbing films may increase manufacturing costs. Therefore, especially for pharmaceutical containers, it is preferable not to use UV-absorbing films, but rather to directly contain UV-blocking substances in the liquid container material, forming a monolayer of UV-blocking substances uniformly dispersed within the container material.

[0089] The liquid container of this invention is made of white (or translucent) synthetic resin, characterized in that it contains titanium dioxide (IV) as a coloring agent. Titanium dioxide (IV) functions as an ultraviolet blocking substance.

[0090] In one embodiment of the invention, a preferred liquid container is a white synthetic resin container, characterized by containing titanium dioxide (IV) and free of any other coloring components besides titanium dioxide (IV). Such a liquid container, according to one embodiment of the invention, is preferred because components in the container material do not dissolve into the liquid contained therein.

[0091] When manufacturing the liquid container of the present invention, there are no particular limitations on the method of adding titanium dioxide (IV). For example, a predetermined amount of titanium dioxide (IV) can be directly incorporated into the base resin for molding. Alternatively, the masterbatch method is also preferred. In the masterbatch method, for example, titanium dioxide (IV) is pre-melted and / or compounded in a small amount of resin to prepare a masterbatch (MB) containing a high concentration of titanium dioxide (IV). By mixing this masterbatch with the base resin, titanium dioxide (IV) can be diluted to a predetermined concentration. In this case, there are no particular limitations on the masterbatch that can be used; for example, Polycool Master: EPH-W3380 (manufactured by Polycol Co., Ltd.) can be used.

[0092] Regarding the light transmittance of the liquid container of the present invention in the ultraviolet region, from the perspective of suppressing the decomposition of effluconazole, the light transmittance in the wavelength range of 200nm to 360nm is preferably 0.20% or less, and more preferably 0.10% or less.

[0093] To achieve a higher light blocking effect in the ultraviolet region, the lower limit of the content of titanium dioxide (IV) in the container of the present invention can be limited.

[0094] In one embodiment of the present invention, the lower limit of the content of titanium dioxide (IV) in the polyethylene liquid preparation container with a thickness of 0.8 mm to 1.0 mm relative to 100 parts by weight of synthetic resin is preferably 0.09 parts by weight, more preferably 0.10 parts by weight, further preferably 0.11 parts by weight, and even more preferably 0.18 parts by weight.

[0095] In this specification, "100 parts by weight of synthetic resin" refers to the total weight of materials forming the container of the present invention, such as base resin, titanium dioxide (IV), or masterbatch.

[0096] On the other hand, regarding the light transmittance of the liquid container in the visible light region according to one embodiment of the present invention, from the perspective of visually confirming the remaining amount of liquid inside the container, the light transmittance at a wavelength of 700 nm is preferably 0.25% or more, and more preferably 0.40% or more.

[0097] In another embodiment of the present invention, regarding the light transmittance of the liquid container in the visible light region, the light transmittance in the wavelength range of 700nm to 780nm is preferably 0.25% or more, and more preferably 0.40% or more.

[0098] To ensure light transmittance in the visible light region, the upper limit of the content of titanium dioxide (IV) in the container of the present invention can be limited.

[0099] In one embodiment of the present invention, the upper limit of the content of titanium dioxide (IV) in the polyethylene liquid preparation container with a thickness of 0.8 mm to 1.0 mm relative to 100 parts by weight of synthetic resin is preferably 0.33 parts by weight, more preferably 0.30 parts by weight, further preferably 0.27 parts by weight, and even more preferably 0.22 parts by weight.

[0100] Therefore, one preferred embodiment of the liquid container of the present invention is a container made of synthetic resin, which has a light transmittance of less than 0.20% in the wavelength range of 200 to 360 nm and a light transmittance of more than 0.25% in the wavelength range of 700 nm.

[0101] Another preferred embodiment of the liquid container of the present invention is a container made of synthetic resin, wherein the light transmittance in the wavelength range of 200-360nm is less than 0.20%, and the light transmittance in the wavelength range of 700-780nm is more than 0.25%.

[0102] Another preferred embodiment of the liquid container of the present invention is a container made of synthetic resin, wherein the light transmittance in the wavelength range of 200-360nm is less than 0.10%, and the light transmittance in the wavelength range of 700nm is more than 0.25%.

[0103] Another preferred embodiment of the liquid container of the present invention is a container made of synthetic resin, wherein the light transmittance in the wavelength range of 200-360nm is less than 0.10%, and the light transmittance in the wavelength range of 700-780nm is more than 0.25%.

[0104] Another preferred embodiment of the liquid container of the present invention is a container made of synthetic resin, wherein the light transmittance in the wavelength range of 200-360nm is less than 0.20%, and the light transmittance in the wavelength range of 700nm is more than 0.40%.

[0105] Another preferred embodiment of the liquid container of the present invention is a container made of synthetic resin, wherein the light transmittance in the wavelength range of 200-360nm is less than 0.20%, and the light transmittance in the wavelength range of 700-780nm is more than 0.40%.

[0106] Another preferred embodiment of the liquid container of the present invention is a container made of synthetic resin, wherein the light transmittance in the wavelength range of 200-360nm is less than 0.10%, and the light transmittance in the wavelength range of 700nm is more than 0.40%.

[0107] Another preferred embodiment of the liquid container of the present invention is a container made of synthetic resin, wherein the light transmittance in the wavelength range of 200-360nm is less than 0.10%, and the light transmittance in the wavelength range of 700-780nm is more than 0.40%.

[0108] One preferred embodiment of the liquid container of the present invention is a container made of synthetic resin, which contains 0.09 to 0.33 parts by weight of titanium dioxide (IV) relative to 100 parts by weight of synthetic resin.

[0109] One preferred embodiment of the liquid container of the present invention is a container made of synthetic resin, which contains 0.10 to 0.30 parts by weight of titanium dioxide (IV) relative to 100 parts by weight of synthetic resin.

[0110] One preferred embodiment of the liquid container of the present invention is a container made of synthetic resin, which contains 0.11 to 0.27 parts by weight of titanium dioxide (IV) relative to 100 parts by weight of synthetic resin.

[0111] One preferred embodiment of the liquid container of the present invention is a container made of synthetic resin, which contains 0.18 to 0.22 parts by weight of titanium dioxide (IV) relative to 100 parts by weight of synthetic resin.

[0112] As described above, the liquid container of one embodiment of the present invention is a container that can solve two contradictory problems. That is, according to one embodiment of the present invention, by precisely controlling the light transmittance in both the ultraviolet and visible light regions, a liquid container can be provided that can both suppress the decomposition of ciproconazole caused by ultraviolet light and allow for easy visual confirmation of the remaining amount of contents.

[0113] Furthermore, in this specification, "light transmittance in the wavelength range of X to Y nm" refers to the light transmittance when any wavelength is selected within the entire wavelength range of X to Y nm.

[0114] In addition, light transmittance can be measured, for example, using a commercially available spectrophotometer (U-3310, manufactured by Hitachi, Ltd.). Furthermore, "transmittance spectrum" refers to a spectrum obtained by expressing the measured light transmittance within an arbitrary wavelength range as a continuous spectrum.

[0115] The structure of the brush component in the applicator of the present invention is not particularly limited as long as it achieves the effects of the present invention, but it is preferable to have a reference structure. Figure 2B The structure of the brush component is described.

[0116] Specifically, in one embodiment of the present invention, a preferred brush bristle component is a columnar brush bristle component formed by bundling together multiple synthetic fibers made of polyester.

[0117] In another embodiment of the present invention, a preferred brush bristle component is a columnar brush bristle component formed by bundling together multiple synthetic fibers made of polyethylene or nylon.

[0118] The diameter of the synthetic fiber used in this invention is preferably 7-50 μm, more preferably 10-30 μm.

[0119] In addition, the synthetic fibers used in this invention can be bonded together with adhesives.

[0120] The density of the adhesive used for bonding synthetic fibers is preferably in the range of 0.15 to 0.65 (porosity 85% to 35%), more preferably in the range of 0.25 to 0.50 (porosity 75% to 50%).

[0121] In this specification, "density" refers to the proportion of synthetic fibers and adhesives used to bond them in a unit cross-sectional area, based on a cross-section cut perpendicular to the fiber direction of the bristle component.

[0122] When the synthetic fiber density is less than 0.15, due to the large number of flow paths (voids) for the medicine, excessive liquid will be discharged when the container is inverted to drain it. In addition, due to the small number of structural parts, it is difficult to maintain the strength of the columnar bristle component, making it prone to damage.

[0123] On the other hand, when the density of synthetic fibers is greater than 0.65, the flow path (pores) of the medicine becomes smaller, making it difficult for the medicine to penetrate, thus hindering the smooth application of the medicine.

[0124] The preferred volume of the bristle component depends on factors such as the volume and viscosity of the liquid that permeates and remains within the columnar bristle component via capillary action. If the viscosity of the liquid used in this invention is low, it is preferable to increase the volume of the columnar bristle component. In one embodiment of this invention, the preferred volume of the bristle component is 400–600 mm². 3 The range.

[0125] The brush bristle component described in the embodiments of the present invention described later is obtained by forming polyethylene fibers with a fiber diameter of 18 μm and a fineness of 3.3 dtex into a columnar shape with a density of 0.42 (porosity of 58%). The volume of the columnar brush bristle component used in this embodiment is 490 mm². 3 .

[0126] In another embodiment of the present invention, the brush bristle component may also be a pen-shaped brush bristle component formed by welding one end of a synthetic fiber bundle.

[0127] In one embodiment of the present invention, the applicator may further include a bottom cylindrical retainer. The structure of the applicator with the bottom cylindrical retainer in one embodiment of the present invention is not particularly limited as long as it achieves the effects of the present invention, but it is preferable to have a reference... Figure 2C The structure described has a bottomed cylindrical retainer.

[0128] A bottomed cylindrical retainer is used to hold the brush bristle component and reliably connect it to the liquid container.

[0129] The bottomed cylindrical retainer is cylindrical, and the brush component is inserted inside it. At this point, the inner surface of the bottomed cylindrical retainer fits tightly against the outer surface of the brush component, with no structural gaps. Furthermore, the outer surface of the bottomed cylindrical retainer is liquid-tightly fitted into the opening of the liquid container without any gaps. This prevents liquid leakage.

[0130] The bottom of the bottom cylindrical retainer has a fine hole, which serves as a flow path for the liquid to flow from the liquid container to the bristle component.

[0131] In one embodiment of the invention, when the applicator is held with the bristle component side down, the liquid filling the liquid container seeps through the pores into the interior of the bottomed cylindrical holder and reaches one end face of the bristle component (the side held by the bottomed cylindrical holder). The liquid reaching the end face of the bristle component then reaches the other end face of the bristle component (the side to be applied to the nail) through capillary action. This allows the liquid to be applied to the nail.

[0132] The discharge rate of the liquid agent can be increased or decreased depending on the shape and size of the fine holes located at the bottom of the bottomed cylindrical retainer. The position, number, shape, and size of the fine holes can be appropriately set according to the viscosity and other properties of the liquid agent used. For example, in addition to circles, ellipses, polygons, parallelograms, etc., can be selected according to the purpose and application.

[0133] In addition, the size of the fine hole is based on the plane parallel to the bottom of the bottom cylindrical retainer, and the maximum hole diameter is preferably in the range of 0.5 to 5 mm, more preferably in the range of 0.9 to 1.3 mm.

[0134] The applicator described in the embodiments of this specification described later has a bottomed cylindrical holder with the above-mentioned features, and a small hole at the center of its bottom is circular (1.1 mm in diameter).

[0135] Furthermore, the "good user experience" of the applicator of this invention means that when the user dispenses the liquid from the applicator, the liquid can be smoothly applied to the entire affected nail without being applied too much or too little. For example, the applicator can be considered to have a good user experience when the amount applied in a single application is not affected by the usage environment (e.g., temperature) and / or the user's grip strength.

[0136] <2> Liquid In this invention, "liquid preparation" refers to a formulation prepared by dissolving, emulsifying, or suspending active ingredients and additives in a solvent. The liquid preparation container and applicator of this invention are suitable for liquid preparations containing effluconazole as an active ingredient. This liquid preparation container and applicator are used to treat onychomycosis by applying effluconazole liquid to the entire affected nail once daily.

[0137] As one embodiment of "liquid containing efconazole", the following liquid can be used: a liquid in which efconazole and one or more pharmaceutically acceptable additives are dissolved in water, an organic solvent or a mixture of water and an organic solvent as needed.

[0138] In this invention, the content of icoconazole is 10% relative to the total weight of the liquid.

[0139] The liquid preparation filled in the container of the present invention may, as needed, contain pharmaceutically acceptable additives. As additives, it may contain antioxidants, preferably butylated hydroxytoluene (BHT) and ethylenediaminetetraacetic acid (EDTA).

[0140] The solvent used in the liquid filling the container of the present invention may be water, an organic solvent, or a mixture of water and an organic solvent. Examples of usable organic solvents include ethanol, propylene glycol, glycerol, triacetin, isopropanol, isopropyl adipate, alkyl lactates, cyclomethyl silicones, and mixtures of two or more of the above organic solvents.

[0141] Ethanol is the preferred solvent in this invention. Therefore, the preferred liquid preparation for filling the container of this invention is an ethanol solution containing 10% icofol by weight of the total liquid preparation.

[0142] Example The present invention will be further described in detail below with reference to the embodiments, but the present invention is not limited to the following embodiments.

[0143] <Manufacturing Example> Each liquid container was manufactured according to Table 1. Specifically, a specified amount of MB (masterbatch: Polycool Master, EPH-W-3380) was added to the base resin (Novatec® HD, HB332R), and after melt mixing, each container was blow molded. Each liquid container was non-flexible and rigid. In addition, the thickness of the container sidewall was measured as the container thickness.

[0144] After filling each container with 10% effluconazole solution, a bottomed cylindrical retainer with inserted brush bristles is fitted into each container, and the cap is screwed on tightly, thereby obtaining each applicator. The aforementioned 10% effluconazole solution uses a liquid composed of the following components: 0.00025 wt% disodium EDTA, 1.00 wt% purified water, 0.10 wt% anhydrous citric acid, 0.10 wt% BHT, 10.00 wt% C12-15 alkyl lactate, 12.00 wt% diisopropyl adipate, 13.00 wt% cyclomethyl silicone, 10.00 wt% effluconazole, and an appropriate amount of 95% ethanol (totaling 100.00 wt%).

[0145] Table 1 ※1 MB (Master Material): Polycool Master, EPH-W-3380 (manufactured by Polycol Co., Ltd.)

[0146] ※In Table 2, the transmittance of the container for light from 200nm to 360nm is shown at the maximum value at 360nm.

[0147] <Experimental Example 1> <Light stability test> Photostability tests were conducted on the containers of Comparative Examples 1-2 and Examples 1-3 shown in Table 1. These containers were various types with different thicknesses and titanium dioxide (IV) contents. 4 mL of 10% ivermectin solution was filled into each container, and a bottomed cylindrical retainer with a brush attachment was fitted into each container. The sample with the cap screwed on was placed horizontally in the photostability testing apparatus and stored under the following conditions. The photostability testing apparatus used was a "Stability Testing Apparatus for Photostability Testing" (LTL-200A-14WCD, manufactured by Nagano Scientific Corporation).

[0148] Light source: D65 fluorescent lamp Illuminance: 2000 lux Temperature: 25±2℃ Humidity: 60%RH±5%RH Samples were taken for quality evaluation at the start of the experiment (before D65 fluorescent lamp irradiation) and at approximately 1.2 million lux·hr (25 days). Impurity content was analyzed using high-performance liquid chromatography (HPLC). The peak areas of the sample solutions were determined by automatic integration, and their contents were calculated using area normalization. For each of the three containers in Comparative Examples 1-2 and Examples 1-3, the maximum peak value of newly generated unknown impurity peaks in the samples was determined, and their average content was calculated.

[0149] In the photostability test of this specification, if the maximum value of the newly generated unknown impurity peak is below 0.20% under irradiation of 1.2 million lux·hr, the photostability is considered guaranteed and marked as "A" (A rating) in the photostability column. Conversely, if the maximum value exceeds 0.20%, the photostability is considered not guaranteed and marked as "B" (B rating) in the photostability column. The results are shown in Table 2.

[0150] Table 2 *RRT (Relative Retention Time): Retention time relative to the retention time of icoconazole. The container of Comparative Example 1, under irradiation at 1.2 million lux·hr, showed a maximum value of 0.28% in the newly generated unknown impurity peak, which did not meet the photostability evaluation criteria (Evaluation B) of this test. The containers of Comparative Example 2 and Examples 1-3 all met the photostability evaluation criteria (Evaluation A). Furthermore, in Examples 1-3, the total impurity content under irradiation at 1.2 million lux·hr was 0.08-0.15%. These results indicate that the containers of Examples 1-3 can stably store effluconazole solution.

[0151] As shown in Table 2, the light transmittance in the 200nm–360nm wavelength range decreases with increasing titanium dioxide (IV) content. Furthermore, the light transmittance in the 200nm–360nm wavelength range also decreases with increasing container thickness.

[0152] Comparative Example 2, Example 1, Example 2, and Example 3 all demonstrated stable preservation of the effluconazole liquid. However, it was confirmed that Comparative Example 1 could not suppress the increase of impurities from effluconazole. Therefore, the photostability of the effluconazole liquid filled in each container depends on the light transmittance in the wavelength range of 200 nm to 360 nm. When the light transmittance in the wavelength range of 200 nm to 360 nm is below 0.20%, the effluconazole liquid can be stably preserved.

[0153] The above results confirm that the light transmittance in the wavelength range of 200nm to 360nm is crucial for the increase of impurities in evaporative fluoride liquid caused by light exposure. By blocking light in this wavelength range, the decomposition of evaporative fluoride can be inhibited.

[0154] Here, Examples 4 and 5, not shown in Table 2, are similar to Example 3 in that they are almost opaque to ultraviolet light (Table 1). Furthermore, the container thickness of Example 4 is the same as that of Examples 2 and 3, which meet the light stability test evaluation criteria, and its titanium dioxide (IV) content is higher than that of Examples 2 and 3. Additionally, the container titanium dioxide (IV) content of Example 5 is the same as that of Examples 1 and 3, which meet the light stability test evaluation criteria, and its sidewall thickness is higher than that of Examples 1 and 3. Therefore, it can be understood that the containers of Examples 4 and 5 are more stable to light and meet the light stability test evaluation criteria (A evaluation) of this specification.

[0155] <Experimental Example 2> <Light transmittance test> Using scissors, the sidewalls of the containers from Comparative Examples 1-4 and Examples 1-5 were cut into rectangles of approximately 1 cm × 2 cm. The cut bottle fragments were placed on the light-emitting side of the spectrophotometer sample cell holder, and the light transmittance spectrum in the wavelength range of 200–800 nm was measured. The measurement results and the evaluation results regarding whether the remaining amount of iefluconazole solution could be visually confirmed externally when filling the containers are shown in Table 3.

[0156] Table 3 The containers used for the light transmittance test were also various containers with different thicknesses and titanium dioxide (IV) contents, and nine types of containers as shown in Table 3 were used. Table 3 also lists the light transmittance of each container at 700 nm, the light transmittance in the 700 nm–780 nm wavelength range, and whether the amount of liquid filling the container could be visually confirmed from the outside. In Comparative Examples 2–4, the internal liquid was difficult to visually confirm, while in Comparative Examples 1 and Examples 1–5, the internal liquid could be visually confirmed. Furthermore, the light transmittance spectra of all containers showed an increasing trend in the 700 nm–780 nm wavelength range, and the light transmittance at 700 nm was the minimum value in this range. The light transmittance spectra of the containers in Comparative Examples 1–4 and Examples 1–5 are also shown in Table 3. Figures 3 to 14 .exist Figures 3 to 14 In the diagram, the horizontal axis represents wavelength (nm) and the vertical axis represents light transmittance (%).

[0157] As shown in Table 3, the light transmittance in the 700nm–780nm wavelength range decreases with increasing titanium dioxide (IV) content in the container. Furthermore, the light transmittance in the 700nm–780nm wavelength range also decreases with increasing container thickness.

[0158] The visibility of the effluconazole solution filled in each container from the outside of the container is related to the light transmittance in the wavelength range of 700 nm to 780 nm. In Comparative Example 1 and Examples 1, 2, 3, 4, and 5, where the light transmittance at a wavelength of 700 nm is 0.25% or higher, the contents can be visually identified. On the other hand, in Comparative Examples 2, 3, and 4, where the light transmittance at a wavelength of 700 nm is less than 0.25%, the contents cannot be visually identified.

[0159] Based on the above results, it can be confirmed that the container for effluconazole solution must have a transmittance of at least 0.25% for light at a wavelength of 700nm.

[0160] <Experimental Example 3> <Smear Test> 4 mL of 10% effluconazole solution was filled into the containers of Comparative Example 2 and Example 3 shown in Table 1. A bottomed cylindrical retainer with inserted brush bristles was fitted into each container, and the cap was tightened to obtain the samples. After measuring the weight of the bottle before application, the solution was applied to five patches with an area of ​​4 cm². 2The entire surface of the stainless steel sheet was covered. This process was repeated twice, equivalent to applying the solution to 10 stainless steel sheets, and the weight of the bottle after application was measured. This operation assumes the amount of solution applied to 10 toenails. The amount applied was calculated by subtracting the weight of the bottle after application from the weight of the bottle before application. The entire container was held during application, with three different angles relative to the application surface: 90°, 45°, and 10–20°. Five tests were performed on each container at each application angle, and the average application amount and standard deviation were calculated.

[0161] The results of this experiment are shown in Table 4 below.

[0162] Table 4 Both containers provided a suitable amount of application and could function appropriately as applicators. Comparing the application amounts of Comparative Example 2 and Example 3, it was observed that Example 3 showed a tendency for application amount to be suppressed. Furthermore, regarding the application angle, it was observed that the closer the container was to a vertical position, the greater the application amount (90° ≥ 45° ≥ 10~20°).

[0163] <Experimental Example 4> <Discharge test (dripping time) and user experience test> Prepare five containers for each of Comparative Example 2 and Example 3. Fill these containers with 4 mL of 10% ciproconazole solution and fit the bottomed cylindrical retainer with the bristle part into the container for testing.

[0164] Using a silicone tube connected to a constant-temperature water bath, fix each container in an inverted position, heat to 32°C, and observe the dripping of the liquid. Count the number of droplets and measure the time required for each drip.

[0165] In Comparative Example 2 and Example 3, the time required from the start of the experiment to the first drop was 22.4 seconds and 41.5 seconds, respectively. Furthermore, the time required from the first drop to the second drop was 2.6 seconds and 6.3 seconds, respectively. The number of drops required to stop dripping within one minute was 13 drops and 8 drops, respectively.

[0166] It can be seen that, when comparing Comparative Example 2 (sidewall thickness: 0.7 mm) with Example 3 (sidewall thickness: 0.9 mm), the latter requires a longer dripping time.

[0167] Next, 80 evaluators conducted a sensory evaluation of Comparative Examples 2 and 4 regarding their usability. The results showed that Comparative Example 4 did not experience excessive liquid leakage, resulting in smoother liquid application. Here, since the titanium dioxide (IV) content in the container material does not affect the usability, it is considered that Examples 2-4, which have the same sidewall thickness as Comparative Example 4, have an equally excellent usability as Comparative Example 4.

[0168] In summary, Examples 1-5 are preferred because they can stably fill 10% effluconazole solution and the contents can be visually confirmed. Examples 2-4 are particularly preferred from a user experience perspective.

[0169] Industrial availability The container of the present invention maintains a good user experience while blocking light wavelengths that promote the photodecomposition of iefluconazole, and the remaining amount of liquid inside the container can be visually confirmed from the outside. Therefore, it has practical value as a container for filling iefluconazole liquid.

[0170] Explanation of reference numerals in the attached figures S fills space 1 Liquid container 2. Bottomed cylindrical retainer 3 columnar bristle components 4 blocks 11 Liquid container body 11a sidewall 11b bottom wall 12 Liquid container neck 14 Openings 15 thread 21 Bottomed cylindrical retainer body 22 Annular flange portion 23 bottom 24 fine pores 31 columnar bristle component main body 32 columnar bristle components neck 33. Front end of columnar bristle component 35 Support components 100 applicator

Claims

1. A liquid container that can be filled with 10% effluconazole solution, wherein, The liquid container is a container formed from a synthetic resin containing titanium dioxide (IV). Its light transmittance in the wavelength range of 200-360nm is less than 0.20%, and its light transmittance at a wavelength of 700nm is greater than 0.25%, and the amount of liquid filled in the liquid container can be visually confirmed from the outside.

2. The liquid container according to claim 1, characterized in that, The liquid container is a generally cylindrical polyethylene container with an opening at the top. It is a container consisting of a single layer of polyethylene in which at least titanium dioxide (IV) is uniformly dispersed, and it is a non-flexible rigid container.

3. The liquid container according to claim 1 or 2, wherein, The internal volume of the liquid container is 8-12 mL, and the sidewall thickness of the liquid container is 0.8-1.0 mm.

4. The liquid container according to any one of claims 1 to 3, characterized in that, It contains 0.09 to 0.33 parts by weight of titanium dioxide (IV) relative to 100 parts by weight of synthetic resin.

5. The container according to any one of claims 1 to 4, characterized in that, It contains 0.10 to 0.30 parts by weight of titanium dioxide (IV) relative to 100 parts by weight of synthetic resin.

6. The liquid container according to any one of claims 1 to 5, characterized in that, It contains 0.18 to 0.22 parts by weight of titanium dioxide (IV) relative to 100 parts by weight of synthetic resin.

7. The liquid container according to any one of claims 1 to 6, characterized in that, It contains no coloring components other than titanium dioxide (IV).

8. The liquid container according to any one of claims 1 to 7, wherein, In the liquid container, the light transmittance in the wavelength range of 700–780 nm is above 0.25%.

9. The liquid container according to any one of claims 1 to 8, wherein, In the liquid container, the light transmittance in the wavelength range of 700–780 nm is above 0.40%.

10. The liquid container according to any one of claims 1 to 9, wherein, In the liquid container, the light transmittance in the wavelength range of 200–360 nm is below 0.10%.

11. The liquid container according to any one of claims 1 to 10, wherein it is not packaged with an ultraviolet-absorbing film.

12. An applicator comprising: Liquid container as claimed in any one of claims 1 to 11; Synthetic fiber bundles are integrated into columnar brush bristle components; as well as A bottomed cylindrical retainer, having a cylindrical body and a bottom, is located between the liquid container and the columnar bristle component. The bottomed cylindrical retainer is liquid-tightly fitted into the opening of the liquid container. The bottom of the bottomed cylindrical retainer has at least one fine hole. The columnar bristle component is inserted into the cylindrical body of the bottomed cylindrical retainer. The liquid can flow from the liquid container to the columnar bristle component through the fine holes, so that when the container is inverted during use, the liquid will penetrate into the columnar bristle component and can be applied to the user's nails.

13. The applicator according to claim 12, wherein, The columnar bristle component is formed by bundling synthetic fibers with a fiber diameter ranging from 7 to 50 μm at a density ranging from 0.25 to 0.

50. The bottomed cylindrical retainer has a circular fine hole with a diameter of 0.9 to 1.3 mm.

14. The applicator according to claim 12 or 13, characterized in that, When the applicator filled with 4 mL of the liquid is inverted at 32°C, the number of drops required to stop dripping within 1 minute is 7 to 10.

15. A method for photostabilizing icoconazole, comprising the step of filling a liquid container containing 10% icoconazole solution into a liquid container according to any one of claims 1 to 11 or an applicator according to any one of claims 12 to 14.

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