JP2023098370A - External pharmaceutical preparation - Google Patents

Abstract

To provide a technique capable of applying a uniform and appropriate amount of an external preparation containing loxoprofen or salt thereof onto a desired portion at each application while suppressing excessive administration of the external preparation.SOLUTION: An external pharmaceutical preparation includes (a) external preparation and (b) a container housing the external preparation (a), where the external preparation (a) contains at least one kind selected from the group consisting of loxoprofen and salt thereof, ethanol and thickener, the B type viscosity of the external preparation (a) is 10 mPa s or more and 400 mPa s or less, a TI value (η1/η2) of the external preparation (a) is more than 1.00 and less than 2.00, and the container (b) has a body part and a neck part equipped with an application part of the external preparation (a), and the neck part is inclined with respect to a longitudinal direction central axis of the body part.SELECTED DRAWING: Figure 1

Description

The present invention relates to external preparations.

Patent Document 1 (Japanese Unexamined Patent Application Publication No. 2021-172638) describes a technique for blending loxoprofen or a salt thereof in an external preparation. In the document, the object is to provide an external pharmaceutical preparation containing loxoprofen and/or a salt thereof and a monohydric lower alcohol, and capable of suppressing overdosage exceeding 2.0 g per administration. (Paragraph 0007), and as a technique for solving this, loxoprofen and / or a salt thereof, a monoterpene and / or capsaicinoid, and a monohydric lower alcohol are included, and the dosage per dose is 2.0 g The topical pharmaceutical formulation set below is described (claim 1).

Japanese Patent Application Laid-Open No. 2021-172638

In Patent Document 1, it is essential to add monoterpene and/or capsaicinoid to the formulation in order to prevent overdosage. For this reason, according to the same document, while it is said that a strong cold sensation, hot sensation or burning sensation can give the user a sufficient feeling of use (paragraph 0018), users who are sensitive to skin irritation, etc. There is room for improvement in terms of making it possible to use it even if there is.

INDUSTRIAL APPLICABILITY The present invention provides a technique that makes it easy to apply a uniform and appropriate amount of an external preparation to a desired site each time it is applied while suppressing excessive administration of an external preparation containing loxoprofen or a salt thereof.

According to the present invention, the following external preparations are provided.
[1] An external preparation comprising (a) an external preparation, and (b) a container containing the external preparation (a),
The external preparation (a) is
at least one selected from the group consisting of loxoprofen and salts thereof;
ethanol;
a thickening agent;
contains
The B-type viscosity of the external preparation (a) measured at 25° C. with a B-type viscometer is 10 mPa·s or more and 400 mPa·s or less,
Thixotropy defined as the ratio of the viscosity η1 of the topical preparation (a) at a shear rate of 5 s ^-1 to the viscosity η2 of the topical preparation (a) at a shear rate of 100 s ^-1 , measured using a rheometer at 25°C The index (TI) value (η1/η2) is more than 1.00 and less than 2.00,
The external preparation, wherein the container (b) is a container having a body and a neck provided with an application part of the external preparation (a), wherein the neck is inclined with respect to the longitudinal central axis of the body. .
[2] The thixotropic index (TI) value (η1/η3) defined as the ratio of the viscosity η1 to the viscosity η3 of the external preparation (a) at a shear rate of 30 s ⁻¹ is more than 1.00 and less than 1.50. The external preparation according to [1].
[3] the container (b) has a capacity of 5 g or more and 100 g or less;
The external preparation according to [1] or [2], wherein the B-type viscosity is 10 mPa·s or more and 350 mPa·s or less.
[4] Any one of [1] to [3], wherein the content of ethanol in the external preparation (a) is 10% by mass or more and 75% by mass or less with respect to the entire external preparation (a) The external preparation described in .

ADVANTAGE OF THE INVENTION According to this invention, while suppressing the overdosing of the topical preparation containing loxoprofen or its salt, it can be made easy to apply a uniform and appropriate amount of topical preparations to a desired site|part at every application.

It is a perspective view showing an example of composition of a container in an embodiment. It is a figure for demonstrating the measuring method of the coating amount in an Example.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described with reference to the drawings. The drawings are schematic diagrams and do not necessarily correspond to actual dimensional ratios.
In this embodiment, the composition can contain each component alone or in combination of two or more.
In the present specification, "-" indicating a numerical range represents above and below, and includes both numerical values at both ends.

In this embodiment, the external preparation includes (a) an external preparation and (b) a container containing the external preparation (a). The external preparation (a) contains at least one selected from the group consisting of loxoprofen and salts thereof, ethanol, and a thickening agent, and is measured at 25 ° C. with a Brookfield viscometer (a ) has a B-type viscosity of 10 mPa s or more and 400 mPa s or less, and is measured using a rheometer at 25° C., and the viscosity of the external preparation (a) at a shear rate of 100 s ⁻¹ and a shear rate of 5 s ⁻¹ relative to the viscosity η2 of the external preparation (a) The thixotropic index (TI) value (η1/η2) defined by the ratio of the viscosity η1 of the external preparation (a) in is more than 1.00 and less than 2.00. The container (b) has a body and a neck provided with an application part for the external preparation (a), and is a container in which the neck is tilted with respect to the central axis in the longitudinal direction of the body.

In the present embodiment, the external preparation comprises a topical preparation (a) containing specific components and having specific ranges of B-type viscosity and TI value (η1/η2), and Since it is combined with the container (b) with an inclined neck, the dose of the external preparation (a) can be controlled to an appropriate amount. Therefore, it is easy to apply a uniform and appropriate amount of the topical preparation (a) to the desired site each time it is applied, while suppressing excessive administration of the topical preparation (a).

Here, the reason why the administration amount of the external preparation (a) can be controlled by using the external preparation (a) and the container (b) in combination is considered as follows.
First, regarding the physical properties of the external preparation, if the B-type viscosity (static viscosity) of the external preparation is too high, it will be difficult to take out the external preparation from the container, and there is a concern that the ease of application of the external preparation will decrease.
Also, if both the B-type viscosity (static viscosity) and the TI value (η1/η2) (dynamic viscosity) of the topical preparation are too large, it will be difficult to remove the topical preparation from the container, and in addition, it will not be possible to apply the topical preparation to the affected area. There is a concern that the ease of application to the target site will decrease.
On the other hand, if both the B-type viscosity (static viscosity) and the TI value (η1/η2) (dynamic viscosity) of the topical preparation are too small, the topical preparation tends to come out of the container excessively, and immediately after application to the target site. There is a concern that it will easily drip and the topical agent will be difficult to stay on the target site.
Further, according to studies by the present inventors, by using the external preparation (a) and the container (b) in this embodiment in combination, the B-type viscosity (static viscosity) of the external preparation (a) can be adjusted to a specific range. This makes it easy to take out a suitable amount of the topical preparation (a) from the container, to easily retain the topical preparation (a) in the application site, and to further increase the TI value (η1/η2) (movement It has been newly found that the external preparation (a) can be easily and evenly applied to the skin or the like each time it is applied, when the external preparation (a) has a specific viscosity).
The external preparation (a) and the container (b) will be described in more detail below.

(External agent (a))
The external preparation (a) is specifically an external preparation for skin, and more specifically an external preparation applied to the skin. The external preparation (a) is a composition containing at least one selected from the group consisting of loxoprofen and salts thereof, ethanol, and a thickener.

In the external preparation (a), the B-type viscosity measured at 25° C. with a B-type viscometer is 10 mPa·s or more, preferably 12 mPa·s or more, more preferably 14 mPa·s or more, from the viewpoint of suppressing overdosage. s or more.
In addition, from the viewpoint of enhancing ease of application to a desired site, the B-type viscosity of the external preparation (a) is 400 mPa·s or less, preferably 350 mPa·s or less, more preferably 300 mPa·s or less, and further preferably 300 mPa·s or less. It is preferably 200 mPa·s or less, and more preferably 100 mPa·s or less.

Here, the B-type viscosity of the external preparation (a) is specifically measured using a B-type viscometer (eg, DV3T, manufactured by BROOKFIELD, Spindle LV-2, etc.) at a rotation speed of 200 rpm (viscosity of 150 mPa s or 30 rpm (those with a viscosity of 150 mPa·s or more), a measurement time of 1 minute, and an average value of n=2.

^The TI value ⁽ η1/η2) is more than 1.00, preferably 1.01 or more, more preferably 1.02 or more, because the liquid does not easily drip and stays on the affected area.
In addition, the TI value (η1/η2) is less than 2.00, preferably 1.80 or less, and more preferably 1.80 or less, since the external preparation (a) can be easily and evenly applied to the skin each time it is applied. It is preferably 1.50 or less, and still more preferably 1.20 or less.

The viscosity η1 of the external preparation (a) is preferably 5 mPa·s or more, more preferably 10 mPa·s or more, because it is less likely to drip and stays more easily on the affected area.
In addition, from the viewpoint of enhancing ease of application to a desired site, the viscosity η1 of the external preparation (a) is 500 mPa·s or less, preferably 450 mPa·s or less, more preferably 350 mPa·s or less, and even more preferably 350 mPa·s or less. It is 200 mPa·s or less, and more preferably 100 mPa·s or less.

The TI value (η1/η3), which is defined as the ratio of the viscosity η1 to the viscosity η3 of the external preparation (a) at a shear rate of 30 s ⁻¹ , is less likely to drip and more likely to remain in the affected area, and therefore preferably exceeds 1.00. , more preferably 1.01 or more, and still more preferably 1.02 or more.
In addition, the TI value (η1/η3) is preferably less than 1.50, more preferably 1.40, because the external preparation (a) can be easily and evenly applied to the skin or the like each time it is applied. Below, more preferably 1.30 or less, still more preferably 1.20 or less.

Here, the dynamic viscosity of the topical preparation (a) is measured, for example, by using a rheometer (for example, MCR302 manufactured by Anton Paar), setting a sample of the topical preparation (a) in a measuring section heated to 25° C., and measuring the shear rheology. According to the measurement method, the shear rate is continuously changed from 1 (1/s) to 100 (1/s) for 275 seconds, and the measurement can be performed under the following conditions.
Plate type: Cone plate Plate diameter: 50mm
Measurement temperature: 25°C

Next, the components of the external preparation (a) will be explained.
(at least one selected from the group consisting of loxoprofen and salts thereof)
Loxoprofen and salts thereof specifically include loxoprofen and loxoprofen salts. Here, the loxoprofen salt may be a hydrate salt.
Specifically, the loxoprofen salt is at least one selected from loxoprofen sodium and loxoprofen sodium dihydrate, preferably loxoprofen sodium dihydrate.
In addition, loxoprofen in the present embodiment is listed in the Japanese Pharmacopoeia 18th Edition as loxoprofen sodium hydrate.

The total content of loxoprofen and its salt in the topical preparation (a) may be appropriately set according to the efficacy to be provided, and for example, preferably 0.1 mass with respect to the entire topical preparation (a). % or more, more preferably 0.5 mass % or more, and still more preferably 0.8 mass % or more.
In addition, the total content of loxoprofen and its salt in the topical preparation (a) may be appropriately set according to the efficacy to be provided, and for example, preferably 10% by mass based on the entire topical preparation (a). or less, more preferably 8.5% by mass or less, even more preferably 5% by mass or less, and even more preferably 3% by mass or less.

(ethanol)
In this embodiment, ethanol (also referred to as ethyl alcohol or alcohol) is listed in Pharmaceutical Excipient Dictionary 2021 (Yakuji Nippo, 2021), for example, solubilizers, bases, preservatives, solvents, solubilizers. It is used in the external preparation (a) for use as an agent. Ethanol with an ethanol content of 99.5% by volume or more is also called anhydrous ethanol, and ethanol in the present embodiment also includes this.

The content of ethanol in the topical preparation (a) is preferably 10% by mass or more, more preferably 20% by mass or more, based on the total amount of the topical preparation (a), because the topical preparation (a) dries easily in a short time after application. More preferably 30% by mass or more, still more preferably 40% by mass or more, and even more preferably 42.5% by mass or more.
In addition, from the viewpoint of reducing skin irritation, ethanol in the external preparation (a) is preferably 75% by mass or less, more preferably 70% by mass or less, and still more preferably 60% by mass of the total external preparation (a). % by mass or less, more preferably 50% by mass or less, and even more preferably 47.5% by mass or less.

(thickener)
The thickening agent is not limited as long as it imparts a specific viscosity and a specific TI value to the external preparation. Examples include hydroxyethylcellulose, hydroxypropylcellulose, hypromellose (hydroxypropylmethylcellulose), carboxymethylcellulose, and carmellose. Cellulose derivatives such as sodium (sodium carboxymethylcellulose), hydroxyethylmethylcellulose, methylcellulose, ethylcellulose; other polysaccharides such as xanthan gum, pectin, guar gum, roasted bean gum, carrageenan, sodium alginate; carboxyvinyl polymers; and macrogol (polyethylene glycol). ) or two or more selected from the group consisting of
The thickening agent may be a component that is used as a thickening agent, a thickening agent, an adhesive, an adhesion enhancer, etc. in the field of external preparations.

From the viewpoint of more stably suppressing excessive administration of the topical preparation (a) and from the viewpoint of facilitating application of the topical preparation (a) to a desired site, the thickening agent is preferably a cellulose, Cellulose derivatives are more preferred, and hypromellose is even more preferred.

The methoxy group content in hypromellose is, for example, about 27.0 to 30.0%, preferably about 28.0 to 30.0%.
Also, the amount of hydroxypropoxy groups in hypromellose is, for example, about 4.0 to 12.0%, preferably about 7.0 to 12.0%.

The viscosity of a 2% aqueous solution of hypromellose at 20° C. (Japanese Pharmacopoeia) is preferably 50 mPa·s or more, more preferably 3000 mPa·s or more, and still more preferably 5000 mPa·s or more, from the viewpoint of suppressing overdosage. is.
Moreover, from the viewpoint of enhancing ease of application to a desired site, the viscosity of hypromellose is preferably 50000 mPa·s or less, more preferably 20000 mPa·s or less.

In this embodiment, the external preparation (a) may contain components other than the components described above.
(water)
For example, the external preparation (a) may further contain water.
The content of water in the topical preparation (a) can be, for example, the balance after removing components other than water in the topical preparation (a).
In addition, since the water-soluble base is easily dissolved, the content of water in the external preparation (a) is preferably 20% by mass or more, more preferably 30% by mass, based on the total external preparation (a). % or more, more preferably 40 mass % or more.
In addition, from the viewpoint of facilitating drying of the topical preparation (a) in a short time after application, the content of water in the topical preparation (a) is preferably 70% by mass or less relative to the total topical preparation (a). , more preferably 60% by mass or less, and still more preferably 50% by mass or less.

(l-menthol)
In addition, the external preparation (a) may further contain l-menthol. l-Menthol is listed in the Japanese Pharmacopoeia 18th Edition and the Dictionary of Pharmaceutical Excipients 2021.
From the viewpoint of analgesic assistance, the content of l-menthol in the external preparation (a) is preferably 0.01% by mass or more, more preferably 0.5% by mass or more, relative to the total external preparation (a). , more preferably 2% by mass or more.
In addition, from the viewpoint of reducing skin irritation, the content of l-menthol in the topical preparation (a) is preferably 10% by mass or less, more preferably 7.5% by mass, based on the total topical preparation (a). % or less.

In addition, the external preparation (a) may contain drugs and pharmaceutical additives other than the above-mentioned components, which are usually used in pain relief and antiphlogistic skin preparations for external use.

Such drugs include, for example, glycyrrhizic acid and its salts, anti-inflammatory agents such as glycyrrhetinic acid, diphenhydramine or its salts, diphenimidazole, antihistamines such as chlorpheniramine maleate, tocopherol acetate, benzyl nicotinate and the like. Blood circulation improving ingredients, dl-camphor, d-camphor, nonanoic acid vanillylamide (nonylic acid vanillylamide), terpenes containing menthol and thymolborneol, essential oils containing terpenes such as turpentine oil, peppermint oil and eucalyptus oil, hot pepper extract, hot pepper topical stimulating ingredients such as tinctures and capsaicin; crude drug ingredients such as arnica tincture, belladonna extract, horse chestnut seed or extract; bactericidal ingredients such as isopropylmethylphenol; astringents and antiphlogistic agents such as zinc oxide; Drugs can be blended within a range that does not impair the effects of the present invention.

In addition, pharmaceutical additives include, for example, those added as necessary in order to further improve content stability over time and feel during use. Specific examples of pharmaceutical additives include bases, solubilizers, wetting agents, adhesives, pH adjusters, antioxidants, cooling agents, surfactants, stabilizers, emulsifiers, curing agents and the like.

Examples of the base include styrene/isoprene/styrene copolymer; polyisobutylene; liquid paraffin; partially neutralized polyacrylic acid; polyvinyl alcohol (partially saponified), propylene glycol, dipropylene glycol, macrogol, 1, Polyhydric alcohols such as 3-butylene glycol, glycerin, and D-sorbitol are included.

Wetting agents include, for example, sodium dl-pyrrolidonecarboxylate and polysorbate 40 solution.

Examples of adhesives include dibutylhydroxytoluene and hydrogen rosin glycerin ester.

pH adjusters include, for example, hydrochloric acid, sodium hydroxide, potassium hydroxide, citric acid, malic acid, tartaric acid, gluconic acid, lactic acid, organic acids, organic amines (e.g., triethanolamine, diisopropanolamine, etc.), phosphorus An acid or the like can be used.
As a method for adjusting the pH of the external preparation (a), for example, a pH adjusting agent and a general-purpose base used in external preparations are mixed to dissolve or disperse to adjust the pH to a desired value.
The pH is not limited as long as it does not adversely affect the skin, and is usually adjusted to pH 3.5 to 8.5, preferably pH 4 to 8, more preferably pH 4 to 7.5.

Antioxidants include, for example, ascorbic acid, ascorbic palmitate, sodium bisulfite, sodium pyrosulfite, sodium edetate, citric acid hydrate, anhydrous citric acid, dibutylhydroxytoluene, butylhydroxyanisole, benzotriazole, gallic acid propyl acid.

Examples of the cooling agent include menthol including l-menthol, terpenes such as camphor, peppermint oil, and eucalyptus oil.

As the surfactant, a nonionic surfactant may be used, or an ionic surfactant may be used.
Examples of nonionic surfactants include propylene glycol mono-fatty acid ester, ethylene glycol mono-fatty acid ester, glycerin mono-fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, sucrose fatty acid ester, methylglucoside fatty acid ester, alkylpolyglucoside. , polyhydric alcohol fatty acid ester or polyhydric alcohol alkyl ether such as polyethylene glycol fatty acid ester; polyoxyethylene alkyl ether, polyoxyethylene alkylphenyl ether, polyoxyethylene phytosterol, polyoxyethylene phytostanol, polyoxyethylene polyoxypropylene alkyl Polyoxyethylene ethers such as ethers; Polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene monofatty acid ester, polyethylene glycol difatty acid ester, polyoxyethylene glycerin fatty acid ester, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80 , polyoxyethylene sorbitol fatty acid ester, polyoxyethylene methyl glucoside fatty acid ester, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, etc. Nonionic surfactants such as oxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyethylene vegetable oil, polyoxyethylene alkyl ether fatty acid ester, ether ester such as polyoxyethylene polyoxypropylene glycol; sodium lauryl sulfate, cetyl Ionic surfactants such as sodium sulfate; higher alcohols such as octyldodecanol; Examples of polyoxyethylene alkyl ethers in the present invention include polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene oleyl ether, polyoxyethylene behenyl ether and the like.

In this embodiment, the dosage form of the external preparation (a) may be one that satisfies the viscosity characteristics described above and can be applied to the skin or the like from the application portion of the container (b), for example, a liquid preparation. When the external preparation (a) is produced, it can be produced, for example, by using appropriate additives according to the dosage form and following the usual methods described in the Japanese Pharmacopoeia 18th Edition.

Here, in the present embodiment, in order to obtain the external preparation (a) that satisfies the above-described conditions for B-type viscosity and TI value, it is important to devise a manufacturing method that differs from conventional techniques. Selection of the type of constituent components of the external preparation (a), selection of the blending amount of each component, and the like can be mentioned.
More specifically, by appropriately selecting the type and amount of the thickening agent contained in the topical preparation (a) and controlling the amounts of the other constituents, each viscosity characteristic is within the desired range. A stopping resin composition can be obtained.

(Container (b))
FIG. 1 is a perspective view showing an example of the configuration of a container (b) in this embodiment.
The container 100 shown in FIG. 1 includes a container body 110 and a lid 120 detachably attached to the container body 110 .

The container body 110 contains the external preparation (a). The container body 110 has a trunk portion 101 and a neck portion 103 communicating with the trunk portion 101 . The neck portion 103 is inclined with respect to the central axis of the body portion 101 in the longitudinal direction.
The angle α formed by the central axis of the longitudinal direction of the trunk 101 and the central axis of the neck 103 in the extending direction suppresses excessive administration of the topical agent (a) and allows an equal and appropriate amount of the topical agent to be applied each time it is applied. From the viewpoint of ease of application and ease of application of the external preparation (a), the angle is, for example, about 25 to 75°, preferably about 30 to 60°, more preferably about 30 to 50°. .

The neck portion 103 is provided with an applicator portion 105 for applying the external preparation (a) to the target site.
Further, the outer circumference of the neck portion 103 and the inner surface of the lid 120 may each be provided with, for example, a screw thread, and the lid 120 may be attached to the container body by fitting these screw threads.

Materials for container body 110 and lid 120 include, for example, one or more selected from the group consisting of resin, glass, and metal.
Among these, specific examples of resins include thermoplastic resins, and more specifically, polyethylene such as high-density polyethylene and low-density polyethylene, polyolefin such as polypropylene (PP); polyester such as polyethylene terephthalate; be done.
Moreover, aluminum is mentioned as an example of a metal.
The materials of container body 110 and lid 120 may be the same or different.

Examples of the material of the application portion 105 include polyurethane such as polyurethane foam such as soft urethane foam, styrene foam, natural rubber, and polyethylene. The application section 105 may be made of a porous material.

Although the capacity of the container 100 is not limited, it is preferably 5 g or more, more preferably 15 g or more, and still more preferably 20 g or more from the viewpoint of easy application of an appropriate amount of the external preparation.
In addition, the capacity of the container 100 is preferably 100 g or less from the viewpoints of preventing excessive administration of the topical preparation (a) and facilitating the uniform and appropriate amount of the topical preparation each time it is applied, and from the viewpoint of portability. , more preferably 80 g or less, and still more preferably 50 g or less.
It is also preferable that the container (b) has a capacity of 5 g or more and 100 g or less, and the external preparation (a) has a B-type viscosity of 10 mPa·s or more and 350 mPa·s or less.

Although the embodiments of the present invention have been described above with reference to the drawings, these are examples of the present invention, and various configurations other than those described above can also be adopted.

EXAMPLES The present embodiment will be specifically described below with reference to Examples, but the present embodiment is not limited to these Examples.

(Examples 1 to 5, Comparative Examples 1 to 3)
In this example, an external preparation was prepared and evaluated.

(Method for producing external preparation)
The components shown in Table 1 were stirred, mixed and dissolved to obtain compositions (external preparations) 1 to 6. Each obtained composition was filled in an applicator container for an external antiphlogistic analgesic ("implementation container" to be described later) to obtain each external preparation.

(Measurement of B-type viscosity)
Using a Brookfield viscometer (DV3T, manufactured by BROOKFIELD), fill 80 mL of each composition into a glass vial bottle (Mighty Vial No. 8, manufactured by Maruem), and measure the viscosity of each composition under the following conditions. (Measuring time 1 minute, average value of n=2).
Rotation speed: 200 rpm when the B-type viscosity is less than 150 mPa·s, and 30 rpm when the B-type viscosity is 150 mPa·s or more.
Spindle: Spindle LV-2 was used when the viscosity was over 15 mPa·s, and spindle LV-1 was used when the viscosity was 15 mPa·s or less.
Measurement temperature: 25°C

(Measurement of dynamic viscosity)
Using a rheometer (manufactured by Anton Paar, MCR302), each composition (external preparation) was set in a measurement section heated to 25°C, and a shear rate of 1 (1/s) to 100 (1/s) was measured by a shear rheology measurement method. s) continuously for 275 seconds and measured under the following conditions.
Plate type: Cone plate Plate diameter: 50mm
Measurement temperature: 25°C

(evaluation)
(Average coating amount)
As an indicator of the ease of application of each topical preparation, here, the ability to apply an appropriate amount of each composition (topical preparation), the average applied amount of the topical preparation obtained in each example was measured by the following procedure.
1. Each external preparation (each example) was prepared by adjusting the content of the external preparation to approximately 8%, approximately 40%, and approximately 80% with respect to the container capacity of 100%.
2. Each external preparation was applied to an arm model (manufactured by Beaulux, No. 47), as shown in FIG. The coating amount was calculated from the difference in mass.
3. 2. above. was repeated 6 times for each content (approximately 8%, approximately 40%, approximately 80%), and from the results of a total of 18 coating amounts obtained, the average coating amount per time was obtained, and the following was evaluated according to the criteria of Table 2 shows the evaluation results.
○: Average coating amount is more than 0.05 g (content liquid is easy to come out, moderate amount is easy to apply)
×: Average coating amount is 0.05 g or less (content liquid is difficult to come out, it is difficult to apply an appropriate amount)

In addition, in Table 2, the details of the working containers of Examples and Comparative Examples are as follows.
A container suitable for each filling amount was selected as the test container, and the test was carried out.
Specifically, in Example 2, when the container capacity is 100%, the filling amount at approximately 80% filling is set to 80 g, and in other examples and comparative examples, the test is performed at approximately 80% filling amount of 25 g. bottom.
In the case of the containers with neck inclination "yes", the inclination angle of the neck with respect to the longitudinal central axis of the body was set at 45°, and in the containers with neck inclination "no", the inclination angle was set at 0°.
In addition, as the application portion, an inner plug made of two kinds of materials, polyurethane and polyethylene, was used. Specifically, in Example 4, an application part made of polyethylene was used, and in other examples and comparative examples, an application part made of polyurethane was used.

(relative standard deviation of all data)
The relative standard deviation (RSD) was determined as an index for facilitating the uniform application of the topical preparation each time while suppressing excessive administration of the topical preparation.
Specifically, the procedure for measuring the average coating amount described above, 3. The RSD of each topical preparation (each example) was calculated from the results of the amount applied for a total of 18 times, and the variation in the amount applied per application was evaluated according to the following criteria. Table 2 shows the evaluation results.
○: RSD is less than 1.0 (easy to apply an even amount each time, easy to control the dosage)
×: RSD is 1.0 or more (difficult to apply an even amount each time, difficult to control the dosage)

In Table 1, the unit of component amount is % by mass. "Phosphoric acid (1 → 2)" is an aqueous solution of phosphoric acid prepared so that the ratio is the same as when 1 mL of phosphoric acid is dissolved in water to make 2 mL, and "hydrochloric acid (1 → 2)" The same is true for Details of the components listed in Table 1 are as follows.
Loxoprofen sodium hydrate: manufactured by KOLON LIFE SCIENCE Co., Ltd. Anhydrous ethanol: manufactured by Imazu Pharmaceutical Co., Ltd. Hypromellose: METOLOSE 60SH-10000, manufactured by Shin-Etsu Chemical Co., Ltd., methoxy group content: 28.0-30.0%, hydroxypropoxy group content: 7.0%. 0-12.0%, viscosity of 2% aqueous solution at 20 ° C. 10000 mPa s
Hydroxypropyl cellulose: HPC-H, manufactured by Nippon Soda Co., Ltd. l-Menthol: manufactured by Suzuki Minka Co., Ltd.

From Table 2, in each example, it was possible to apply a uniform and appropriate amount of the external preparation to the desired site (arm model) while suppressing excessive administration.
It should be noted that when applying to the arm model, it was possible to apply more smoothly when the material of the application part was made of polyurethane than when it was made of polyethylene.

100 Container 101 Body 103 Neck 105 Applicator 110 Container body 120 Lid 200 Arm model

Claims (4)

(a) a topical preparation, and (b) a container containing the topical preparation (a), wherein
The external preparation (a) is
at least one selected from the group consisting of loxoprofen and salts thereof;
ethanol;
a thickening agent;
contains
The B-type viscosity of the external preparation (a) measured at 25° C. with a B-type viscometer is 10 mPa·s or more and 400 mPa·s or less,
Thixotropy defined as the ratio of the viscosity η1 of the topical preparation (a) at a shear rate of 5 s ^-1 to the viscosity η2 of the topical preparation (a) at a shear rate of 100 s ^-1 , measured using a rheometer at 25°C The index (TI) value (η1/η2) is more than 1.00 and less than 2.00,
The external preparation, wherein the container (b) is a container having a body and a neck provided with an application part of the external preparation (a), wherein the neck is inclined with respect to the longitudinal central axis of the body. . A thixotropic index (TI) value (η1/η3) defined as a ratio of the viscosity η1 to the viscosity η3 of the external preparation (a) at a shear rate of 30 s ⁻¹ is more than 1.00 and less than 1.50. Item 1. The external preparation according to item 1. The capacity of the container (b) is 5 g or more and 100 g or less,
The topical preparation according to claim 1 or 2, wherein the B-type viscosity is 10 mPa·s or more and 350 mPa·s or less. 4. The topical preparation according to any one of claims 1 to 3, wherein the content of said ethanol in said topical preparation (a) is 10% by mass or more and 75% by weight or less with respect to said topical preparation (a) as a whole. .

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