JP7214331B2 - Pharmaceutical composition - Google Patents

Description

TECHNICAL FIELD The present invention relates to a pharmaceutical composition containing ethyl aminobenzoate and a quaternary ammonium salt, while suppressing yellowing caused by exposure to light and having excellent formulation stability.

Ethyl aminobenzoate is known as a local anesthetic and is widely used to relieve local itching and pain of mucous membranes and skin. , have been variously considered. For example, Patent Document 1 reports that a local anesthetic composition containing a basic local anesthetic such as ethyl aminobenzoate and its hydrochloride can have both rapid-acting and sustained local anesthetic action. there is

In addition, quaternary ammonium salts such as cetylpyridinium chloride and benzalkonium chloride are known as bactericidal agents and are widely used in various pharmaceuticals. Various studies have also been conducted on formulation of products. For example, Patent Document 2 contains 0.05 to 2% by weight of a quaternary ammonium salt, 0.1 to 4% by weight of chlorpheniramine maleate, and 0.01 to 10% by weight of a chloride ion source. It has been reported that a topical pharmaceutical composition characterized by

In recent years, pharmaceutical compositions have been required to have multiple functions, and pharmaceutical formulations using a combination of a local anesthetic and a disinfectant have also been developed. However, in order to put a pharmaceutical composition into practical use, it is necessary to consider not only functionality but also formulation stability. At present, the formulation stability of products has not been sufficiently studied.

JP-A-8-259464 JP 2010-159251 A

The inventors of the present invention have conducted studies to put a pharmaceutical composition containing ethyl aminobenzoate and a quaternary ammonium salt into practical use. We faced a new problem that the appearance properties could not be maintained and the formulation stability was poor.

Therefore, an object of the present invention is to provide a formulation technology that can suppress yellowing caused by light exposure and provide excellent formulation stability in a pharmaceutical composition containing ethyl aminobenzoate and a quaternary ammonium salt. be.

The present inventors have made intensive studies to solve the above problems, and found that one or more of polyhydric alcohols, monoterpenes, polyvinylpyrrolidone, and hydroxyethyl cellulose are added together with ethyl aminobenzoate and quaternary ammonium salts. It has been found that a pharmaceutical composition formulated in combination can be inhibited from yellowing caused by exposure to light and have excellent formulation stability. The present invention has been completed through further studies based on such findings.

That is, the present invention provides inventions in the following aspects.
Section 1. A pharmaceutical composition containing (A) ethyl aminobenzoate, (B) a quaternary ammonium salt, and (C) at least one selected from the group consisting of polyhydric alcohols, monoterpenes, polyvinylpyrrolidone, and hydroxyethylcellulose. thing.
Section 2. Item 2. The pharmaceutical composition according to Item 1, wherein the component (B) is cetylpyridinium chloride.
Item 3. Item 3. The pharmaceutical composition according to Item 1 or 2, wherein the polyhydric alcohol is propylene glycol and/or glycerin.
Section 4. Item 4. The pharmaceutical composition according to any one of Items 1 to 3, wherein the monoterpene is menthol.
Item 5. Item 5. The pharmaceutical composition according to any one of Items 1 to 4, comprising a polyhydric alcohol and polyvinylpyrrolidone as the component (C).
Item 6. Item 6. The pharmaceutical composition according to any one of Items 1 to 5, which is a pharmaceutical for external use or a pharmaceutical for mucosa.
Item 7. A method for inhibiting yellowing caused by light exposure of a pharmaceutical composition comprising ethyl aminobenzoate and a quaternary ammonium salt, comprising:
At least one selected from the group consisting of (C) polyhydric alcohols, monoterpenes, polyvinylpyrrolidone, and hydroxyethylcellulose, together with (A) ethyl aminobenzoate and (B) quaternary ammonium salts, in the pharmaceutical composition to combine the
A method for inhibiting yellowing caused by light exposure of said pharmaceutical composition.

INDUSTRIAL APPLICABILITY According to the pharmaceutical composition of the present invention, even when ethyl aminobenzoate and a quaternary ammonium salt coexist, yellowing caused by exposure to light can be suppressed, and excellent formulation stability can be provided.

1. Pharmaceutical composition The pharmaceutical composition of the present invention comprises ethyl aminobenzoate (sometimes referred to as component (A)), a quaternary ammonium salt (sometimes referred to as component (B)), and a polyhydric alcohol. , monoterpene, polyvinylpyrrolidone, and hydroxyethyl cellulose (also referred to as component (C)). The pharmaceutical composition of the present invention is described in detail below.

(A) Ethyl aminobenzoate Ethyl aminobenzoate is a known local anesthetic also called ethyl 4-aminobenzoate, benzocaine and the like.

In the pharmaceutical composition of the present invention, the content of component (A) is not particularly limited, and is appropriately set according to the degree of local anesthetic action to be imparted to the pharmaceutical composition, the formulation form and application of the pharmaceutical composition, etc. For example, 0.1 to 5% by weight, preferably 0.3 to 2% by weight, more preferably 0.3 to 1% by weight.

(B) Quaternary ammonium salt The quaternary ammonium salt used in the present invention is not particularly limited as long as it has a bactericidal action and is pharmaceutically acceptable. cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, dequalinium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, methylbenzethonium chloride, lauroylcolaminoformylmethylpyridinium chloride and the like.

These quaternary ammonium salts may be used singly or in combination of two or more.

Among these quaternary ammonium salts, cetylpyridinium chloride, benzalkonium chloride, and benzethonium chloride are preferred, and cetylpyridinium chloride is more preferred, from the viewpoint of more effectively suppressing yellowing due to exposure to light. be done.

In the pharmaceutical composition of the present invention, the content of the component (B) is not particularly limited, and may be appropriately set according to the degree of bactericidal action to be imparted to the pharmaceutical composition, the formulation form and application of the pharmaceutical composition, and the like. For example, 0.05 to 1% by weight, preferably 0.1 to 0.5% by weight, and more preferably 0.3 to 0.5% by weight.

In the pharmaceutical composition of the present invention, the ratio of component (B) to component (A) is determined according to the respective contents of component (A) and component (B). The amount of component (B) is 10 to 300 parts by weight, preferably 50 to 200 parts by weight, and more preferably 50 to 150 parts by weight.

(C) Polyhydric alcohol, monoterpene, polyvinylpyrrolidone, and/or hydroxyethylcellulose The pharmaceutical composition of the present invention contains polyhydric alcohol, monoterpene, polyvinylpyrrolidone, and/or hydroxyethylcellulose as component (C). . Inclusion of the component (C) makes it possible to suppress yellowing that occurs when ethyl aminobenzoate and a quaternary ammonium salt coexist and are exposed to light.

The type of polyhydric alcohol used as component (C) is not particularly limited as long as it is pharmaceutically acceptable. Examples include 1,3-butylene glycol, ethylene glycol, propylene glycol, isoprene glycol, and diethylene glycol. , dipropylene glycol, and polyethylene glycol; and trihydric alcohols such as glycerin. These polyhydric alcohols may be used singly or in combination of two or more.

Among these polyhydric alcohols, propylene glycol and glycerin are preferred from the viewpoint of more effectively suppressing yellowing due to exposure to light.

The monoterpene used as the component (C) is a known component having a structure containing two isoprene units in the molecule and having a cooling effect and the like. The type of monoterpene used as component (C) is not particularly limited as long as it is pharmaceutically acceptable. monoterpene; aldehyde monoterpene such as citral, citronellal, perillaldehyde and safranal; ketone monoterpene such as camphor, menthone, carbomenthone and ionone; These monoterpenes may be d-, l-, or dl-forms when optical isomers are present. These monoterpenes may be used singly or in combination of two or more.

Moreover, in the present invention, the monoterpene may be used in the form of an essential oil containing the monoterpene. The essential oil containing monoterpene can be appropriately selected from known ones and used. Examples of essential oils containing menthol include peppermint oil, peppermint oil, and spearmint oil. In addition, the description about the content and ratio of monoterpene in this specification is the value converted into the amount of monoterpene contained in the said essential oil, when using the essential oil containing a monoterpene.

Among these monoterpenes, alcoholic monoterpenes are preferred, menthol is more preferred, and 1-menthol is particularly preferred, from the viewpoint of more effectively suppressing yellowing due to exposure to light.

Polyvinylpyrrolidone used as component (C) is a water-soluble polymer compound obtained by polymerizing N-vinyl-2-pyrrolidone. The weight average molecular weight of polyvinylpyrrolidone used as component (C) is not particularly limited, but is, for example, about 5,000 to 3,000,000, more preferably about 40,000 to 3,000,000. Here, the weight average molecular weight of polyvinylpyrrolidone refers to a value measured by gel filtration chromatography/multi-angle light scattering photometer (GPC/MALLS). The K value (viscosity characteristic value) of polyvinylpyrrolidone is not particularly limited, but one of about 10 to 120 can be preferably used. Moreover, in this invention, a commercial item can be used for polyvinylpyrrolidone. Specific examples of commercial products of polyvinylpyrrolidone include "Eifact K-30PH" manufactured by Daiichi Kogyo Seiyaku Co., Ltd., "Polyvinylpyrrolidone K-30" and "Polyvinylpyrrolidone K-85" manufactured by Nippon Shokubai Co., Ltd., "Polyvinylpyrrolidone K-90", "PVP K-90" manufactured by ISP Japan, and the like.

Hydroxyethyl cellulose used as component (C) is a cellulose derivative whose water solubility is improved by adding ethylene oxide to cellulose. The average number of added moles of ethylene oxide and the average molecular weight of hydroxyethyl cellulose used as component (C) are not particularly limited as long as they are commonly used in the pharmaceutical field. Examples thereof include those having a viscosity of 500 mPa·s or more, preferably 500 to 50000 mPa·s in a weight percent aqueous solution (20° C.). Here, the viscosity is measured using a Brookfield viscometer "TOKI SANGYO VISCOMETER TVB-10" (manufactured by Toki Sangyo Co., Ltd.), rotor: M3 or M4 (rotational speed: 12 to 30 rpm, time : 1 min, unit: mPa·s). Moreover, in this invention, a commercial item can be used for hydroxyethyl cellulose. Specific examples of commercial products of hydroxyethyl cellulose include "HEC CF-V", "HEC CF-W", "HEC CF-X", "HEC CF-Y" and "HEC" manufactured by Sumitomo Seika Co., Ltd. AH-15F", "HEC AV-15F", "HEC AW-15F", "HEC SW-25F", "HEC Daicel SP500", "HEC Daicel SP600", "HEC Daicel SP850" manufactured by Daicel Finechem Co., Ltd., "HEC Daicel SP900", "NATROSOL 250HX" manufactured by Ashland, and the like.

In the pharmaceutical composition of the present invention, one of polyhydric alcohols, monoterpenes, polyvinylpyrrolidone, and hydroxyethylcellulose may be selected and used as component (C), or two or more may be used in combination. You may

From the viewpoint of more effectively suppressing yellowing due to exposure to light, component (C) is preferably a combination of polyhydric alcohol and polyvinylpyrrolidone, more preferably a combination of propylene glycol and polyvinylpyrrolidone.

When using a combination of polyhydric alcohol and polyvinylpyrrolidone as component (C), the ratio of these is not particularly limited, but from the viewpoint of more effectively suppressing yellowing due to light exposure, polyhydric alcohol The ratio of polyvinylpyrrolidone is usually 0.1 to 20 parts by weight, preferably 0.5 to 10 parts by weight, more preferably 0.5 to 5 parts by weight, per 100 parts by weight.

In the pharmaceutical composition of the present invention, the content of component (C) may be appropriately set according to the type of component (C) used, the formulation form and application of the pharmaceutical composition, etc. For example, (C ) in a total amount of 0.01 to 80% by weight, preferably 0.05 to 70% by weight, more preferably 0.1 to 65% by weight.

More specifically, the content of each type of component (C) includes the following ranges;
If a polyhydric alcohol is used : 1-80% by weight, preferably 5-60% by weight.
- When a dihydric alcohol is used as the polyhydric alcohol: more preferably 1 to 60% by weight, particularly preferably 1 to 50% by weight, most preferably 5 to 40% by weight.
- When a trihydric alcohol is used as the polyhydric alcohol: more preferably 10 to 60% by weight, particularly preferably 30 to 60% by weight, most preferably 30 to 50% by weight.
If a monoterpene is used : 0.01-3% by weight, preferably 0.05-1% by weight, more preferably 0.1-1% by weight.
When polyvinylpyrrolidone is used : 0.05-3% by weight, preferably 0.1-1% by weight, more preferably 0.5-1% by weight.
When using hydroxyethyl cellulose : 0.05-3% by weight, preferably 0.1-1% by weight, more preferably 0.5-1% by weight.

In the pharmaceutical composition of the present invention, the ratio of component (C) to component (A) is determined according to the respective contents of component (A) and component (C). Component (C) is 10 to 20,000 parts by weight, preferably 15 to 18,000 parts by weight.

More specifically, the ratio of each type of component (C) to 100 parts by weight of component (A) includes the following ranges;
When polyhydric alcohol is used : 1,500 to 20,000 parts by weight, preferably 3,000 to 18,000 parts by weight in total.
- When a dihydric alcohol is used as the polyhydric alcohol: the total amount is more preferably 1,500 to 18,000 parts by weight, particularly preferably 3,000 to 18,000 parts by weight, and most preferably 5,000 to 18,000 parts by weight.
- When a trihydric alcohol is used as the polyhydric alcohol: the total amount is more preferably 2,000 to 18,000 parts by weight, particularly preferably 5,000 to 18,000 parts by weight, and most preferably 8,000 to 18,000 parts by weight.
When monoterpene is used : 15 to 500 parts by weight, preferably 15 to 400 parts by weight, more preferably 15 to 350 parts by weight in total.
When polyvinylpyrrolidone is used : the total amount is 10-500 parts by weight, preferably 20-400 parts by weight, more preferably 50-350 parts by weight.
When using hydroxyethyl cellulose : 30 to 500 parts by weight, preferably 50 to 500 parts by weight, more preferably 50 to 400 parts by weight in total.

Lower Alcohol The pharmaceutical composition of the present invention may optionally contain a lower alcohol in order to stably dissolve ethyl aminobenzoate.

The type of lower alcohol used in the present invention is not particularly limited as long as it is pharmaceutically acceptable. lower alcohols; Among these lower alcohols, ethanol is preferred.

These lower alcohols may be used singly or in combination of two or more.

When the pharmaceutical composition of the present invention contains a lower alcohol, the content is not particularly limited, but is, for example, 0.5 to 20% by weight, preferably 1 to 10% by weight, more preferably 5 to 10% by weight. %.

Water A preferred aspect of the pharmaceutical composition of the present invention is that it contains water (that is, an aqueous formulation). In the prior art, when ethyl aminobenzoate and a quaternary ammonium salt coexist in the presence of water, yellowing due to exposure to light tends to occur remarkably. However, the yellowing can be effectively suppressed.

When the pharmaceutical composition of the present invention is made into an aqueous formulation, the content of water is not particularly limited, and may be appropriately set according to the formulation form and application of the pharmaceutical composition, for example 1 to 80% by weight. , preferably 5 to 60% by weight, more preferably 10 to 50% by weight.

Other Ingredients The pharmaceutical composition of the present invention may, if necessary, contain other pharmacological ingredients in addition to the ingredients described above. Such pharmacological components include, for example, antihistamines (diphenhydramine, diphenhydramine hydrochloride, etc.), local anesthetics other than ethyl aminobenzoate (procaine, tetracaine, bupipacaine, mepipacaine, chloroprocaine, proparacaine, meprilcaine or salts thereof, orthocaine , oxethazein, oxypolyethoxydecane, rot extract, percamimpase, tecittdecitin, lidocaine, etc.), antibacterial agents other than quaternary ammonium salts (iodine, povidone iodine, potassium iodide, chlorhexidine gluconate, acrinol, etc.), anti-inflammatory agents (glycyrrhizin) dipotassium acid, glycyrrhetinic acid, indomethacin, felbinac, diclofenac sodium, loxoprofen sodium, etc.), skin protective agents (collodion, castor oil, etc.), blood circulation-promoting ingredients (nonylic acid vanillylamide, benzyl nicotinate, capsaicin, red pepper extract, etc.), vitamins (vitamin A, etc.), mucopolysaccharides (sodium chondroitin sulfate, glucosamine, etc.), and the like.

In addition, the pharmaceutical composition of the present invention may, if necessary, contain base materials and additives other than the components described above in order to obtain a desired formulation form. Such bases and additives are not particularly limited as long as they are pharmaceutically acceptable. , cottonseed oil, peanut oil, lard, squalane, fish oil, etc.), mineral oil (liquid paraffin, paraffin, gelling hydrocarbon, petrolatum, etc.), waxes and waxes (beeswax, carnauba wax, candelilla wax, ceresin, rice wax, microcrystalline wax, etc.), ester oils (isopropyl myristate, isopropyl adipate, diethyl sebacate, isopropyl sebacate, isopropyl palmitate, cetyl palmitate, ethyl oleate, etc.), fatty acid alkyl esters, fatty acids (stearic acid, oleic acid) , palmitic acid, behenic acid, linoleic acid, lanolin, etc.), fatty acid esters (cetyl palmitate, isopropyl palmitate, ethyl linoleate, etc.), lower alcohols (ethanol, propanol, isopropanol, butanol, isobutanol, etc.), higher alcohols ( stearyl alcohol, cetanol, behenyl alcohol, myristyl alcohol, oleyl alcohol, hexadecyl alcohol, lanolin alcohol, etc.), cholesterol, glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, silicone oil (dimethylpolysiloxane, cyclic silicone, etc.) Oil base such as POE (10-50 mol) phytosterol ether, POE (10-50 mol) dihydrocholesterol ether, POE (10-50 mol) 2-octyldodecyl ether, POE (10-50 mol) decyltetradecyl Ether, POE (10-50 mol) oleyl ether, POE (2-50 mol) cetyl ether, POE (5-50 mol) behenyl ether, POE (5-30 mol) polyoxypropylene (5-30 mol) 2- Polyoxyethylene alkyl ethers such as decyltetradecyl ether, POE (10-50 mol) polyoxypropylene (2-30 mol) cetyl ether, their phosphoric acid/phosphate (POE cetyl ether sodium phosphate, etc.), POE (20-60 mol) sorbitan monooleate, POE (10-60 mol) sorbitan monoisostearate, POE (10-80 mol) glyceryl monoisostearate, POE (10-30 mol) glyceryl mono Stearate, POE (20-100 mol)/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, polyethylene glycol dioleate, polyethylene glycol diricinoleate, polyoxyethylene hydrogenated castor oil (5-100), polysorbate (20-85), glycerin fatty acid ester (glyceryl monostearate, etc.), hydrogenated soybeans Surfactants such as phospholipids and hydrogenated lanolin alcohol; cooling agents (menthol, camphor, borneol, peppermint water, peppermint oil, etc.), preservatives (methylparaben, propylparaben, benzoic acid, sodium benzoate, sorbic acid, etc.) , flavoring agents (citral, 1,8-cioneal, citronellal, farnesol, etc.), coloring agents (tar pigments (brown No. 201, blue No. 201, yellow No. 4, yellow No. 403, etc.), cacao pigments, chlorophyll, aluminum oxide etc.), thickeners (sodium alginate, ethylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, xanthan gum, carrageenan, carboxyvinyl polymer, sodium polyacrylate, etc.), pH adjusters (phosphoric acid, hydrochloric acid, citric acid, sodium citrate , succinic acid, tartaric acid, sodium hydroxide, potassium hydroxide, triethanolamine, triisopropanolamine, etc.), wetting agents (dl-sodium pyrrolidonecarboxylate solution, D-sorbitol solution, macrogol, etc.), stabilizers (dibutyl Hydroxytoluene, butylated hydroxyanisole, sodium edetate, sodium metaphosphate, L-arginine, L-aspartic acid, DL-alanine, glycine, sodium erythorbate, propyl gallate, sodium sulfite, sulfur dioxide, chlorogenic acid, catechin, rose Marie extract, etc.), antioxidants, ultraviolet absorbers, chelating agents, adhesives, buffers, solubilizers, solubilizers, preservatives and other additives.

Dosage form The dosage form of the pharmaceutical composition of the present invention is not particularly limited, and may be liquid, semi-solid (gel, ointment, paste, etc.), solid, etc., but is preferably Liquid or semi-solid forms that are aqueous formulations may be mentioned.

In addition, the pharmaceutical composition of the present invention may be any of a pharmaceutical for external use, a pharmaceutical for mucous membrane application, or a pharmaceutical for internal use. Specific examples of pharmaceuticals for external use include gels, creams, lotions, emulsions, liquids, patches, aerosols, ointments, and packs. Specific examples of medicines applicable to mucous membranes include gels, creams, lotions, emulsions, liquids, ointments and the like. Specific examples of medicines for internal use include liquid medicines, jelly medicines, and the like. Preparation into these formulations can be carried out according to known methods described in the Japanese Pharmacopoeia 17th Edition, General Rules for Formulations, etc., by using additives suitable for the formulations.

Among these formulation forms, pharmaceuticals for external use on the skin and pharmaceuticals for mucosa, such as gels, creams, lotions, emulsions and liquids, are preferred.

2. Method for Suppressing Yellowing Furthermore, the present invention provides a method for suppressing yellowing caused by exposure to light of a pharmaceutical composition comprising (A) ethyl aminobenzoate and (B) a quaternary ammonium salt, comprising: (C) at least one selected from the group consisting of polyhydric alcohol, monoterpene, polyvinylpyrrolidone, and hydroxyethyl cellulose.

In the method for suppressing yellowing, the types and contents of (A) to (C) used, the types and contents of other ingredients to be blended, the formulation form of the pharmaceutical composition, etc. are described in the above "1. Pharmaceutical composition It is the same as the case of "thing".

EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to these.

Test example 1. Preparation of Pharmaceutical Compositions Pharmaceutical compositions (external skin preparations, liquid formulations) shown in Tables 1 and 2 were prepared. Specifically, predetermined amounts of ethyl aminobenzoate and l-menthol are respectively dissolved in ethanol, and then added to water together with other ingredients and mixed to form a pharmaceutical composition (external skin drug, liquid formulation). Obtained.

2. Evaluation of formulation stability by light exposure Put each pharmaceutical composition in a screw tube (a transparent glass container with a diameter of 24 mm and a height of 50 mm) and place it in a growth chamber set at 12000 lx · hr and 25 ° C. for 96 hours under irradiation with a fluorescent lamp. left undisturbed. After that, the screw tube was inverted 2-3 times to mix, the appearance of the pharmaceutical composition was visually observed, and the stability of the formulation due to exposure to light was evaluated according to the following criteria.
<Evaluation criteria for formulation stability by light exposure>
⊚: No yellowing is observed, and there is no problem in practical use.
◯: Slight yellowing is observed, but there is no problem in practical use.
Δ: Obvious yellowing is observed, unsuitable for practical use.
x: Significant yellowing is observed, unsuitable for practical use.

3. Results The results obtained are shown in Tables 1 and 2. A pharmaceutical composition in which only ethyl aminobenzoate was dissolved showed no yellowing even when exposed to light (Reference Example 1). However, when ethyl aminobenzoate was allowed to coexist with cetylpyridinium chloride, significant yellowing was observed upon exposure to light (Comparative Example 1). On the other hand, when one or more of glycerin, propylene glycol, menthol, polyvinylpyrrolidone, and hydroxyethyl cellulose are allowed to coexist with ethyl aminobenzoate and cetylpyridinium chloride, yellowing due to light exposure can be greatly improved ( Examples 1-22). In particular, among pharmaceutical compositions evaluated as ◎ for formulation stability due to light exposure, when ethyl aminobenzoate, cetylpyridinium chloride, polyhydric alcohol (especially propylene glycol), and polyvinylpyrrolidone are combined, Remarkable formulation stability was observed.

A pharmaceutical composition (drug for oral mucosa) shown in Formulation Example Table 3 was prepared. When the obtained pharmaceutical compositions were evaluated for formulation stability by exposure to light in the same manner as in the above test examples, yellowing was not observed in any of them.

Claims (5)

(A) ethyl aminobenzoate, (B) cetylpyridinium chloride, benzalkonium chloride, and/or benzethonium chloride, and (C) 1,3-butylene glycol, ethylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene A pharmaceutical composition that contains a polyhydric alcohol selected from the group consisting of glycol and glycerin and is a pharmaceutical composition for external use or mucosa (provided that [i] oil absorption is 0.8 g/g or more and oil absorption/ [ii] 0.3% glycyrrhizic acid, 2% tocophenol acetate, amino A dentifrice composition containing 0.3% ethyl benzoate, 4% cetanol, and 2% light liquid paraffin, and having a blending amount of the oily component of 8.6% by mass, has an oil absorption of 1.14 g / g. , a dentifrice composition containing calcium hydrogen phosphate having an oil absorption/water absorption ratio of 1.14 and an average particle size of 14.7 μm; and [iii] cetylpyridinium salt of diclofenac 0. 50 g, 1.00 g benzocaine, 3.00 g liquid paraffin, 50.0 g polyethylene glycol, 10.0 g white petrolatum, 10.0 g propylene glycol, 5.00 g talc, and 100 g qs sterile purified water. [iv] (a) 0.1 to 1.0% by mass of alginate whose viscosity (20° C.) in a 1% by mass aqueous solution is 5 to 100 mPa s, and (b) 2.0% by mass of carboxyvinyl polymer % or more, and the mass ratio of component (a) to component (b) represented by (b)/(a) is 5 or more; [v] isoconazole and A prophylactic or therapeutic agent for vaginal candidiasis or vulvar candidiasis comprising at least one selected from the group consisting of salts thereof; and [vi] containing luliconazole and/or a pharmaceutically acceptable salt thereof. [vii] lilanafthate and/or pharmaceutically acceptable salts thereof are included ). 2. The pharmaceutical composition according to claim 1, wherein the component (B) is cetylpyridinium chloride. 3. The pharmaceutical composition according to claim 1 or 2, wherein said polyhydric alcohol is propylene glycol and/or glycerin. The pharmaceutical composition according to any one of claims 1 to 3, further comprising polyvinylpyrrolidone. (A) ethyl aminobenzoate; and (B) cetylpyridinium chloride, benzalkonium chloride, and/or benzethonium chloride, and is a pharmaceutical composition for external use or mucous membrane application (provided that [i] oil absorption is 0.8 g/g or more, the oil absorption/water absorption ratio is 1.0 or more, and the average particle size is 25 μm or less; and [ii] glycyrrhizic acid as an oil component. 0.3% dentifrice composition containing 0.3% tocopherol acetate, 0.3% ethyl aminobenzoate, 4% cetanol and 2% light liquid paraffin, and containing 8.6% by mass of the oily component. and a dentifrice composition containing calcium hydrogen phosphate having an oil absorption of 1.14 g/g, an oil absorption/water absorption ratio of 1.14, and an average particle size of 14.7 μm; [iii] 0.50 g cetylpyridinium salt of diclofenac, 1.00 g benzocaine, 3.00 g liquid paraffin, 50.0 g polyethylene glycol, 10.0 g white petrolatum, 10.0 g propylene glycol, 5.00 g talc, and sterile purified [vi] Luliconazole and/or a pharmaceutically acceptable salt thereof) is a method for inhibiting yellowing caused by light exposure. hand,
By further adding (C) a polyhydric alcohol selected from the group consisting of 1,3-butylene glycol, ethylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, and glycerin to the pharmaceutical composition , The above method , wherein the yellowing caused by light exposure of the pharmaceutical composition is inhibited.