JP2017088512A - Emulsion composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an emulsion composition that is stable and has a good feeling in use while comprising butyl fulfenamate.SOLUTION: The present invention provides an emulsion composition comprising butyl fulfenamate and a compound having a cation center and an anion center in a molecule.SELECTED DRAWING: None

Description

  The present invention relates to an emulsified composition that is stable and excellent in use feeling while containing butyl flufenamate.

  Although butyl flufenamate is widely known as a non-steroidal anti-inflammatory agent, there is a problem that it is hardly soluble in water and it is difficult to stably mix it in the preparation. For example, a poorly water-soluble drug comprising a poorly water-soluble drug as a composition containing a poorly water-soluble drug, a transdermal absorption enhancer, and an emulsifier, and having an average particle size of oil droplets of 0.1 μm or less A contained oil-in-water emulsion is known (Patent Document 1). However, in this method, the production is complicated because the emulsified particles have to be refined, and when a large amount of butyl flufenamate is blended, it is still difficult to obtain sufficient stability. Further, even if it can be stabilized, the finely divided emulsified particles are difficult to break and are not sticky and have a poor feeling of use. In the case of a cream or the like, there are also problems such as whitening depending on the composition.

  In addition, compounds with cationic and anionic centers in the molecule, such as betaine surfactants and phospholipids, are commonly used in emulsion compositions, but this stabilizes emulsion systems containing butyl flufenamate. It was not known to make it happen.

  Thus, conventionally, there has been a demand for an emulsified composition which can be prepared more easily, and which is stable and excellent in usability, while containing butyl flufenamate.

JP 2002-193790 A

  The object of the present invention relates to an emulsified composition that contains butyl flufenamate, and is stable and excellent in use feeling. In particular, an object of the present invention is to provide an emulsified composition that can give a firm coating feeling (satisfactory coating feeling) without stickiness at the time of application, and that does not remain white.

  The present inventor has conducted intensive studies to solve the above problems, and by blending both butyl flufenamate and a compound having a cation center and an anion center in the molecule, it is excellent in stability and usability. It was found to be an emulsion composition. The present invention has been completed based on this finding, and has the following embodiments.

(1) Emulsified composition (1-1 ) An emulsified composition containing butyl flufenamate and a compound having a cation center and an anion center in the molecule.
(1-2) The emulsion composition according to (1-1), wherein the compound having a cation center and an anion center in the molecule is at least one selected from the group consisting of betaine surfactants, trimethylglycine and phospholipids. .
(1-3) The content of butyl flufenamate is 1 to 10% by weight, and the content of a compound having a cation center and an anion center in the molecule is 0.01 to 3% by weight (1-1) or The emulsion composition according to (1-2).
(1-4) The emulsified composition according to any one of (1-1) to (1-3), which is an external preparation for skin.

(2) Stabilization method of emulsion composition (2-1) Stabilization method of emulsion composition containing butyl flufenamate, comprising oily composition containing butyl flufenamate having a cation center and an anion in the molecule A method for stabilizing an emulsified composition, comprising mixing and emulsifying an aqueous composition containing a compound having a center.
(2-2) The stabilization method according to (2-1), wherein the compound having a cation center and an anion center in the molecule is at least one selected from the group consisting of betaine surfactants, trimethylglycine and phospholipids. .
(2-3) The content of butyl flufenamate is 1 to 10% by weight, and the content of the compound having a cation center and an anion center in the molecule is 0.01 to 3% by weight (2-1) or (2-2) The stabilization method as described.
(2-3) The stabilization method according to any one of (2-1) to (2-3), wherein the emulsion composition is an external preparation for skin.

  According to this invention, it can be set as the emulsion composition which mix | blended the butyl flufenamate stably, without refine | miniaturizing an emulsion particle. In addition, it is possible to obtain an emulsified composition that can give a firm coating feeling (satisfactory coating feeling) without stickiness at the time of application and that does not remain white. Furthermore, since the step of refining the emulsified particles is not necessarily required, the production equipment can be simplified, and the production can be performed easily and in a short time.

It is a HPLC analysis result of butyl flufenamate.

(1) Emulsion composition The emulsion composition of the present invention is an emulsion composition containing butyl flufenamate and a compound having a cation center and an anion center in the molecule. Hereinafter, each component will be described.

(A) Butyl flufenamate The emulsified composition of the present invention contains butyl flufenamate (hereinafter sometimes referred to as “component (A)”). Butyl flufenamate is commercially available and is known as a non-steroidal anti-inflammatory agent. The alias is also called "Ufenamart".

  The content of the butyl flufenamate in the emulsified composition of the present invention is not particularly limited, but it is preferably 1% by weight or more, more preferably 1 to 10% by weight in 100% by weight of the composition. More preferably, the content is ˜8% by weight. Within this range, an emulsion composition containing a compound having a cation center and an anion center in the molecule, which will be described later, can have further improved stability and usability.

  When using commercially available butyl flufenamate, it is preferable to use a product that does not substantially have a peak seen at a retention time of 35 to 45 minutes in a high performance liquid chromatograph (HPLC) method under the following analysis conditions. By using such a product, the skin sensitization property of the obtained emulsion composition can be suppressed.

(Sample preparation)
Standard solution: Ethanol (95) was added to 1 g of butyl flufenamate to make 100 ml. To 5 ml of the solution, 5 ml of sodium lauryl sulfate solution (mixed with 2.9 g of sodium lauryl sulfate in 500 ml of 0.1% phosphoric acid aqueous solution) was added, and ethanol (95) was further added to make 50 ml. This was used as a standard solution.
Sample solution: To 1 g of commercially available butyl flufenamate, add 5 ml of sodium lauryl sulfate solution (mixed by adding 2.9 g of sodium lauryl sulfate to 500 ml of 0.1% phosphoric acid aqueous solution), and then add ethanol (95). To 50 ml. This was irradiated with ultrasonic waves for 15 minutes and filtered through a membrane filter. This was used as a sample solution.

(Test conditions)
Analysis device: Prominence LC-20AT (manufactured by Shimadzu Corporation)
Detector: UV absorptiometer (measurement wavelength: 254 nm)
Column: L-column ODS (4.6 mm × 150 mm, 5 μm, manufactured by GL Sciences Inc.)
Column temperature: constant temperature around 30 ° C. Mobile phase: methanol / phosphoric acid / water (90 / 0.01 / 9.99)
Flow rate: Adjusted so that the retention time of butyl flufenamate is about 19 minutes using a standard solution (about 0.5 ml / min)
Sample solution injection volume: 10 μL
Analysis time: 60 minutes

(B) Compound having a cation center and an anion center in the molecule In addition to the component (A), the emulsion composition of the present invention contains a compound having a cation center and an anion center in the molecule (hereinafter referred to as “zwitterion”). "Compound" and "(B) component").

  The zwitterionic compound is not particularly limited as long as it is usually used for products applied to the human body such as pharmaceuticals, quasi drugs, and cosmetics. For example, lauryl betaine (lauryldimethylaminoacetic acid betaine) N-alkyl-N, N-dimethylamino acid betaine; fatty acid amide alkyl-N, N-dimethylamino acid betaine such as cocamidopropyl betaine and lauramidopropyl betaine; imidazoline type betaine such as sodium cocoamphoacetate and sodium lauroamphoacetate; alkyldimethyl Alkylsulfobetaines such as taurine; alkylhydroxysulfobetaines such as laurylhydroxysulfobetaine; sulfate-type betaines such as alkyldimethylaminoethanol sulfate; phosphorus such as alkyldimethylaminoethanol phosphate -Type betaine; methacrylic acid derivatives such as polymethacryloylethyldimethylbetaine, N-methacryloyloxyethyl N, N-dimethylammonium-α-methylcarboxybetaine / alkyl methacrylate copolymer; phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin Such as sphingophospholipid, lecithin, lysolecithin, soybean phospholipid, hydrogenated soybean phospholipid, partially hydrogenated soybean phospholipid, egg yolk phospholipid, hydrogenated egg yolk phospholipid, partially hydrogenated egg yolk phospholipid, hydroxylated lecithin, etc. Examples thereof include lipids (there is no particular limitation as long as the compound contains a phospholipid or a similar structure in the molecule); trimethylglycine; amphoteric starch; silicone-based amphoteric surfactant. Among these, when used in an external composition, particularly a skin external composition, in consideration of formulation stability and usability, betaine surfactants, trimethylglycine, phospholipids and the like are preferable. As the lipid, a polymer having 2-methacryloyloxyethyl phosphorylcholine as a structural unit is preferable, and a copolymer of 2-methacryloyloxyethyl phosphorylcholine and a methacrylate ester (for example, butyl methacrylate) is more preferable. In addition, although these zwitterionic compounds may be used individually by 1 type, they can also be used in combination of 2 or more types arbitrarily.

  The content of the zwitterionic compound in the emulsified composition of the present invention is not particularly limited, but it is preferably 0.01% by weight or more, preferably 0.01 to 3% by weight in 100% by weight of the composition. Is more preferable, 0.05 to 2% by weight is more preferable, and 0.1 to 2% by weight is particularly preferable. By adjusting the zwitterionic compound within this range, the stability of the emulsified composition containing butyl flufenamate can be further enhanced, and the composition can be made more excellent in use feeling.

  Further, the content ratio of butyl flufenamate and zwitterionic compound in the emulsified composition of the present invention is not particularly limited, but from the viewpoint of formulation stability and feeling of use, it is zwitterionic with respect to 1 part by weight of butyl flufenamate. It is preferable that it is 0.01-3 weight part of ionic compounds, It is more preferable that it is 0.02-2 weight part, It is further more preferable that it is 0.02-1 weight part, 0.02-0.5 Part by weight is particularly preferred.

(C) Aqueous component The emulsion composition of the present invention is not particularly limited, and examples thereof include an oil-in-water emulsion composition and a water-in-oil emulsion composition. Especially, it is preferable that it is an oil-in-water type emulsion composition from the point of stability and a usability | use_condition. Examples of the aqueous component forming the aqueous phase of the emulsion composition of the present invention include water, monohydric alcohols, polyhydric alcohols and the like.

  The type of water is not particularly limited, and for example, purified water, distilled water, ion exchange water, and the like can be used. The content of water in the emulsion composition of the present invention is usually selected and adjusted from the range of about 10 to 90% by weight, preferably about 20 to 80% by weight, more preferably about 30 to 70% by weight. More preferred.

  As a monohydric alcohol, a C1-C4 monohydric alcohol can be mentioned, for example. Specifically, methanol, ethanol, propanol, isopropanol and the like can be exemplified. A monohydric alcohol may be used individually by 1 type, and may be used in combination of 2 or more types arbitrarily.

  Examples of the polyhydric alcohol include polyhydric alcohols having 2 to 6 carbon atoms and 2 to 3 oxygen atoms. Specifically, ethylene glycol, diethylene glycol, propylene glycol, 1,3-propanediol, dipropylene glycol, 1,3-butylene glycol, 1,2-pentanediol, 1,2-hexanediol, 3-methyl-1 , 3-butanediol, glycerin, sorbitol and the like. Among these, propylene glycol, dipropylene glycol, 1,3-butylene glycol and 1,2-pentanediol are preferable, and 1,3-butylene glycol is more preferable. A polyhydric alcohol may be used individually by 1 type, and may be used in combination of 2 or more types arbitrarily.

  The content (total amount) of monohydric alcohol or polyhydric alcohol in the emulsion composition is usually selected and adjusted from the range of about 1 to 20% by weight, preferably about 1 to 15% by weight, more preferably It is about 2 to 10% by weight.

(D) Oily component As an oily component which forms the oil phase of the emulsion composition of this invention, a liquid oily component can be mentioned at normal temperature (25 degreeC).

  The oily component that is liquid at room temperature is not particularly limited as long as it is acceptable in the fields of pharmaceuticals, quasi-drugs, cosmetics, foods and drinks, for example, silicone oil, mineral oil, vegetable oil, liquid paraffin, liquid wax. And ester oils can also be used. These oil components may be used alone or in combination of two or more.

  The content of the oily component that is liquid at room temperature in the emulsion composition is appropriately selected and adjusted from the range of about 1 to 30% by weight. Preferably it is about 5 to 20 weight%, More preferably, it is about 7 to 15 weight%. When the oily component that is liquid at normal temperature is contained in the emulsified composition at this content, the emulsified state is further stabilized, and a good emulsified state can be maintained for a long period of time.

  The emulsion composition of the present invention can further contain an oily component that is solid at ordinary temperature (25 ° C.). The oily component that is solid at room temperature functions as a base when the emulsified composition is used as a cosmetic such as a concealer-like drug or foundation.

  The oily component that is solid at room temperature is not particularly limited as long as it is acceptable in the fields of pharmaceuticals, quasi drugs, cosmetics, foods and drinks, and the like. Specifically, for example, fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, and behenic acid; waxes such as beeswax, carbana wax, lanolin, lanolin ester, and candelilla wax; cetostearyl alcohol, stearyl Mention may be made of solid alcohols such as alcohol, cetanol (cetyl alcohol), myristyl alcohol, isostearyl alcohol, behenyl alcohol, and lanolin alcohol. Solid alcohols such as cetostearyl alcohol, stearyl alcohol, cetanol (cetyl alcohol), and behenyl alcohol are preferred.

  In addition, hydrocarbon oils such as microcrystalline wax, cholesterol, phytosterol, α-olefin oligomer, gelled hydrocarbon, ceresin wax, solid paraffin, and petroleum jelly can also be used as oil components that are solid at room temperature. Among them, it is preferable to use microcrystalline wax, cholesterol or phytosterol. The oily components that are solid at room temperature may be used alone or in any combination of two or more.

  The content of the oily component that is solid at normal temperature in the emulsion composition of the present invention can be appropriately selected and adjusted from the range of usually about 0.01 to 30% by weight. Preferably it is about 0.05 to 20 weight%, More preferably, it is about 0.05 to 15 weight%. When the oily component that is solid at normal temperature in the emulsified composition is contained in this content, the emulsified state is further stabilized, and a good emulsified state can be maintained for a long period of time. Moreover, the usability | use_condition in an emulsion composition can be improved more.

  The content (total amount) of the oil component (liquid or solid at normal temperature) in the emulsion composition of the present invention is preferably about 1 to 60% by weight, more preferably about 5 to 40% by weight, for the same reason as above. More preferably, it is about 5 to 35% by weight.

(E) Optional component In the emulsion composition of the present invention, other components can be appropriately selected and blended as long as the effects of the present invention are not impaired. For example, additional medicinal ingredients, surfactants other than zwitterionic compounds, diluents commonly used in the preparation of pharmaceutical formulations, pH adjusters (buffering agents), thickeners, stabilizers, preservatives, Various additives such as a corrigent (including a sweetener), a corrigent (including a fragrance), and a colorant can be exemplified.

  Examples of the additional medicinal component include those that do not impair the action and effect of butyl flufenamate, and examples thereof include a moisturizing component, a whitening component, an anti-inflammatory component, a bactericidal component, a vitamin drug, and a herbal medicine component.

  Examples of surfactants other than zwitterionic compounds include nonionic surfactants, cationic surfactants, anionic surfactants, and the like (amphoteric surfactants are included in zwitterionic compounds). From the viewpoints of stability and usability, a nonionic hydrophilic surfactant is preferred. As the nonionic hydrophilic surfactant, polyoxyethylene (hereinafter sometimes abbreviated as “POE”) addition type surfactant, C12-C24 fatty acid glyceryl and sorbitan ester are suitable.

  Examples of the POE addition type surfactant include POE (10-50 mol) phytosterol ether, POE (10-50 mol) dihydrocholesterol ether, POE (10-50 mol) 2-octyldodecyl ether, POE (10-10 mol). 50 mol) decyl tetradecyl ether, POE (10-50 mol) oleyl ether, POE (10-50 mol) cetyl ether, POE (5-30 mol) polyoxypropylene (5-30 mol) 2-decyl tetradecyl ether Polyoxyalkylene alkyl ethers such as POE (10 to 50 mol) polyoxypropylene (2 to 30 mol) cetyl ether, polyoxyethylene poly such as POE (3 to 200 mol) polyoxypropylene (15 to 70 mol) glycol Oxypropylene These phosphates and phosphates (such as POE cetyl ether sodium phosphate); POE hydrogenated castor oil; POE (20-60 mol) monostearate, POE (20-60 mol) sorbitan monooleate, POE (10 -60 mol) sorbitan monoisostearate, POE (10-80 mol) glyceryl monoisostearate, POE (10-30 mol) glyceryl monostearate, POE (20-100) polyoxypropylene-modified silicone, POE-alkyl Modified silicone, polyethylene glycol monolaurate, polyethylene glycol monopalmitate, polyethylene glycol monostearate, polyethylene glycol dilaurate, polyethylene glycol dipalmitate, polyethylene glycol distearate Lumpur, dioleate polyethylene glycol, and the like Jirishinorein acid polyethylene glycol.

  Examples of the C12-C24 fatty acid glyceryl and sorbitan ester include glyceryl oleate, glyceryl stearate, glyceryl palmitate, sorbitan oleate, sorbitan stearate, sorbitan palmitate, and the like. These surfactants may be used alone or in any combination of two or more.

(F) Preparation method and application object of emulsion composition The emulsion composition of this invention can be manufactured in accordance with the normal emulsification method of this industry.

  The types, contents, blending ratios, and the like of various components (essential components, surfactants and other optional components) used in the method for preparing the emulsion composition are as described above. In the preparation of the emulsified composition, the components constituting the aqueous phase or the components constituting the oil phase are mixed, whereby an aqueous composition consisting only of the aqueous phase and an oily composition consisting only of the oil phase can be prepared. (Here, it is preferable that the butyl flufenamate which is the component (A) is contained in the oily composition, and the zwitterionic compound which is the component (B) is contained in the aqueous composition). Next, the emulsion composition can be prepared by mixing and emulsifying the aqueous composition and the oily composition. In addition, at the time of preparation, if necessary, it is heated to a temperature of about 50 to 90 ° C., and the mixing is preferably performed under a predetermined condition using a mixer such as a homogenizer, a homomixer, or a stirrer. .

  The application target of the emulsion composition of the present invention is preferably for external use, that is, skin (including scalp). When the emulsified composition is intended to be applied to the skin and used, the emulsified composition is not limited as long as it is applied to the skin such as cosmetics, quasi-drugs for external use of skin, and pharmaceuticals for external use. For example, it is preferable to use a form suitable for various desired external preparations such as ointment, cream, paste, mousse, gel, jelly, suspension, and emulsion.

  When the emulsified composition of the present invention is used, for example, by applying it to human skin, the amount and frequency of applying the emulsified composition to the skin are not particularly limited. For example, depending on the concentration of butyl flufenamate contained, the age, sex, symptom level, application form, expected level, etc. of the user, an appropriate amount is applied to the skin (especially once to several times a day) It is preferably applied to the site where the symptom occurs.

(2) Method for Stabilizing Emulsified Composition The present invention is a method for stabilizing an emulsion composition containing butyl flufenamate, wherein the oily composition containing butyl flufenamate has a cation center and an anion center in the molecule. There is provided a method for stabilizing an emulsified composition, which comprises mixing and emulsifying an aqueous composition containing a compound having the following formula.

  The types of (A) butyl fenfenamate, (B) zwitterionic compound, (C) aqueous component, (D) oil component and (E) optional component used in the method of the present invention, and the blending ratio thereof are the above ( As described in 1). Therefore, in the said invention, the description of (A)-(E) in said (1) can be used.

  In the stabilization method of the present invention, the preparation method of the target emulsion composition is also as described in (F) of (1) above. Therefore, in the said invention, the description of (F) in said (1) can be used.

  According to the stabilization method of the present invention, as shown in the experimental examples described later, the stability of the emulsion composition containing butyl flufenamate can be improved, so that the appearance and quality of the emulsion composition are stabilized. It becomes possible.

  Hereinafter, the present invention will be specifically described based on experimental examples and examples. However, the present invention is not limited by these.

(1) Preparation of emulsion composition (Examples 1-4, Comparative Examples 1-2) According to the formulation described in Table 1, emulsion compositions were prepared as (i) to (iii) below.
(I) Preparation of oily composition All components described in A were mixed to prepare an oily composition.
(Ii) Preparation of aqueous composition Among the components described in B, 1,3-butylene glycol and glycerin were dissolved in purified water, and then xanthan gum was added and swollen. Finally, a zwitterionic compound was added to prepare an aqueous composition.
(Iii) While heating and stirring the emulsified oily composition at 80 ° C., the aqueous composition was added little by little over about 10 minutes. Thereafter, the mixture was stirred for 5 minutes and cooled to room temperature to obtain an emulsified composition. Immediately after the formulation, it was confirmed that none of the emulsified compositions were separated.

(2) Separation stability evaluation of emulsified composition The emulsified composition (Examples 1-4 and Comparative Examples 1-2) prepared above was used as a vial ("Screw tube No. 5" manufactured by Marum Co., Ltd.) 20.0 ml, height: 55 mm, outer diameter: 27.0 mm)) to a height of 45 mm from the bottom and allowed to stand at 60 ° C. conditions. After standing for 48 hours, the state of separation was confirmed visually (appearance observation). In the case of separation, the height from the bottom of the vial to the separation interface is measured, and the ratio of the height of the separation interface to the initial height (45 mm) is determined as the separation degree (= height of the separation interface (mm ) / Initial height (45 mm) × 100). The obtained results were evaluated based on the following criteria. About Example 1-4 which was excellent in the result on 60 degreeC conditions, the isolation | separation state after leaving still for one month on 50 degreeC conditions was also evaluated. The results are shown in Table 1.
(Evaluation criteria)
☆: Degree of separation is less than 5%.
A: The degree of separation is 5% or more and less than 10%.
○: The degree of separation is 10% or more and less than 15%.
Δ: The degree of separation is 15% or more and less than 20%.
X: The degree of separation is 20% or more.

(3) Usability of emulsified composition About the emulsified composition immediately after the preparation (Examples 1 to 4, Comparative Examples 1 and 2) prepared above, about 10 g of each emulsified composition was obtained by 10 evaluation monitors. It was applied to the arm, and the feeling of use at the time of application (no stickiness) and the feeling after use (the film feeling, no white residue) were evaluated. The evaluation was performed by conducting a questionnaire using Visual Analogue Scale (hereinafter referred to as VAS), which was scored between 1 and 10 points according to the criteria shown below. The survey results were averaged and rounded off to the first decimal place. The results are shown in Table 1.
<No stickiness>
1 point: There is a sticky feeling during application.
10 points: No stickiness when applied.
<Film feeling>
1 point: No coating feeling after coating.
10 points: There is a film feeling after coating.
<No white residue>
1 point: White remains after application.
10 points: No white residue after application.

  As in Comparative Example 1, when butyl flufenamate was contained and no zwitterionic compound was contained, the stability of the emulsified composition was poor and it separated after 48 hours at 60 ° C. Further, as shown in Comparative Example 2, even though it contained a zwitterionic compound but did not contain butyl flufenamate, it was similarly poor in stability and separated. On the other hand, when both butyl flufenamate and a zwitterionic compound are contained, separation can be suppressed even under the harsh conditions of 60 ° C. for 48 hours, and no separation is observed at 50 ° C. for 1 month. It was. In particular, the stability could be further improved by setting the zwitterionic compound in the range of 0.02 to 0.15 parts by weight with respect to 1 part by weight of butyl flufenamate.

  In addition, regarding the feeling of use, when butyl flufenamate was not contained (Comparative Example 2), a good feeling of use was recognized to some extent, but in Comparative Example 1 containing butyl flufenamate, there was no sticky feeling and film feeling. In all cases, the white balance was low. On the other hand, even when butyl flufenamate was contained, when a zwitterionic compound was contained, any feeling of use was satisfactory. In particular, with respect to Examples 2 to 4 in which the zwitterionic compound was in the range of 0.02 to 0.15 parts by weight with respect to 1 part by weight of butyl flufenamate, all were sufficient while suppressing stickiness. It can give a feeling of film (solid feeling of application) and can suppress white residue after application, so it can be used as an emulsified composition that is satisfactory for use in prominent places such as hands and face. It was.

(4) Analysis of butyl flufenamic acid The butyl flufenamic acid used in the emulsion composition was analyzed by the HPLC method under the following conditions. Two types (A, B) were used as butyl flufenamates. The analysis results are shown in FIG.

(Sample preparation)
Standard solution: Ethanol (95) was added to 1 g of butyl flufenamate to make 100 ml. To 5 ml of the solution, 5 ml of a sodium lauryl sulfate solution (a mixture of 2.9 g of sodium lauryl sulfate in 500 ml of 0.1% phosphoric acid aqueous solution) and ethanol (95) were further added to make 50 ml. This was used as a standard solution.
Sample solution: 5 ml of sodium lauryl sulfate solution (mixed by adding 2.9 g of sodium lauryl sulfate to 500 ml of 0.1% phosphoric acid aqueous solution) is added to 1 g of butyl flufenamate, and 50 ml of ethanol (95) is further added. It was. This was irradiated with ultrasonic waves for 15 minutes and filtered through a membrane filter. This was used as a sample solution.

(Test conditions)
Analysis device: Prominence LC-20AT (manufactured by Shimadzu Corporation)
Detector: UV absorptiometer (measurement wavelength: 254 nm)
Column: L-column ODS (4.6 mm × 150 mm, 5 μm, manufactured by GL Sciences Inc.)
Column temperature: constant temperature around 30 ° C. Mobile phase: methanol / phosphoric acid / water (90 / 0.01 / 9.99)
Flow rate: Adjusted so that the retention time of butyl flufenamate is about 19 minutes using a standard solution (about 0.5 ml / min)
Sample solution injection volume: 10 μL
Analysis time: 60 minutes

  As shown in FIG. 1, for flufenamic acid butyl A, a peak was detected in the vicinity of a retention time of 35 to 45 minutes, but for flufenamic acid butyl B, such a peak was not detected.

(5) Skin sensitization test Skin sensitization test was conducted using butyl flufenamates A and B. The test is “TG 442C, OECD Guideline for the Testing of Chemicals, In Chemico Skin Sensitization, Direct Peptide Reactivity Assay (DPRA), dated May 2015, DPRA)”. )

  As a result, in butyl flufenamate A in which a peak was detected at a retention time of 35 to 45 minutes, binding to the peptide (skin sensitization) was observed, but such a peak was not detected. In B, binding to the peptide was suppressed, and skin sensitization was significantly suppressed. Neither butyl flufenamate A nor B affected the stability and feeling of use of the emulsified composition, but butyl flufenamate B is more preferred as the emulsified composition of the present invention from the viewpoint of safety. I understood.

Formulation Examples 1-20

  According to the formulations shown in Tables 2 and 3, an emulsion composition was prepared in the same manner as in Example 1. All were emulsion compositions excellent in stability and usability compared to Comparative Example 1.

Claims (3)

  An emulsified composition containing butyl flufenamate and a compound having a cation center and an anion center in the molecule.   The emulsion composition according to claim 1, wherein the compound having a cation center and an anion center in the molecule is at least one selected from the group consisting of betaine surfactants, trimethylglycine and phospholipids. The emulsified composition according to claim 1 or 2, which is a skin external preparation.