Pharmaceutical composition

Abstract

To provide a pharmaceutical preparation technique which suppresses yellowing due to light exposure and achieves excellent pharmaceutical preparation stability in a pharmaceutical composition containing ethyl aminobenzoate and quaternary ammonium salt.SOLUTION: A pharmaceutical composition, which is produced by blending one or more selected from polyhydric alcohol, monoterpene, polyvinyl pyrrolidone, and hydroxyethyl cellulose together with ethyl aminobenzoate and quaternary ammonium salt, suppresses yellowing due to light exposure and achieves excellent pharmaceutical preparation stability.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition that contains ethyl aminobenzoate and a quaternary ammonium salt, and is suppressed in yellowing caused by light exposure, and has excellent formulation stability.

Background Art

[0002] Ethyl aminobenzoate is known as a local anesthetic and is widely used to relieve local itching and pain of mucous membranes and skin. Conventionally, various formulations of pharmaceutical compositions containing ethyl aminobenzoate have also been studied. 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 onset and persistence of local anesthetic action.

[0003] In addition, quaternary ammonium salts such as cetylpyridinium chloride and benzalkonium chloride are known as bactericides and are widely used in various pharmaceuticals and the like. Conventionally, various formulations of pharmaceutical compositions containing quaternary ammonium salts have also been studied. For example, Patent Document 2 reports that a topical composition characterized by containing 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 can achieve a stable formulation that suppresses crystal formation.

[0004] In recent years, multifunctionality has been demanded for pharmaceutical compositions, and formulation prescriptions that combine local anesthetics and bactericides have also been developed. However, in order to put a pharmaceutical composition into practical use, not only functionality but also sufficient consideration must be given to formulation stability. However, in the prior art, sufficient studies have not been made on the formulation stability of pharmaceutical compositions containing ethyl aminobenzoate and quaternary ammonium salts.

Prior Art Documents

Patent Documents

[0005] [Patent Document 1] Japanese Patent Application Publication No. 8-259464 [Patent Document 2] Japanese Patent Publication No. 2010-159251 [Overview of the project] [Problems that the invention aims to solve]

[0006] The inventors of the present invention conducted research to commercialize a pharmaceutical composition containing ethyl aminobenzoate and a quaternary ammonium salt. However, they encountered a new problem: the topical composition discolored to yellow (yellowing) upon exposure to light, failing to maintain a good appearance and resulting in poor formulation stability.

[0007] Therefore, the object of the present invention is to provide a pharmaceutical composition containing ethyl aminobenzoate and a quaternary ammonium salt that can suppress yellowing caused by light exposure and has excellent formulation stability. [Means for solving the problem]

[0008] The inventors of the present invention conducted diligent research to solve the aforementioned problems and found that a pharmaceutical composition comprising ethyl aminobenzoate and a quaternary ammonium salt combined with one or more elements selected from polyhydric alcohols, monoterpenes, polyvinylpyrrolidone, and hydroxyethylcellulose suppresses yellowing caused by light exposure and exhibits excellent formulation stability. The present invention was completed by further research based on this finding.

[0009] In other words, the present invention provides inventions in the following embodiments. Item 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. Item 2. The pharmaceutical composition according to Item 1, wherein the component (B) is cetylpyridinium chloride. Item 3. The pharmaceutical composition according to item 1 or 2, wherein the polyhydric alcohol is propylene glycol and / or glycerin. Item 4. The pharmaceutical composition according to any one of items 1 to 3, wherein the monoterpene is menthol. Item 5. A pharmaceutical composition according to any one of items 1 to 4, comprising a polyhydric alcohol and polyvinylpyrrolidone as component (C). Item 6. A pharmaceutical composition according to any one of items 1 to 5, which is a topical drug or a drug applied to mucous membranes. Item 7. A method for suppressing yellowing caused by light exposure of a pharmaceutical composition comprising ethyl aminobenzoate and a quaternary ammonium salt, The pharmaceutical composition contains (A) ethyl aminobenzoate and (B) a quaternary ammonium salt, along with (C) at least one selected from the group consisting of polyhydric alcohols, monoterpenes, polyvinylpyrrolidone, and hydroxyethylcellulose. A method for suppressing yellowing of the aforementioned pharmaceutical composition caused by light exposure. [Effects of the Invention]

[0010] According to the pharmaceutical composition of the present invention, even when ethyl aminobenzoate and a quaternary ammonium salt are present together, yellowing caused by light exposure can be suppressed, and excellent formulation stability can be achieved. [Modes for carrying out the invention]

[0011] 1. Pharmaceutical composition The pharmaceutical composition of the present invention is characterized by containing ethyl aminobenzoate (sometimes referred to as component (A)), a quaternary ammonium salt (sometimes referred to as component (B)), and at least one selected from the group consisting of polyhydric alcohols, monoterpenes, polyvinylpyrrolidone, and hydroxyethylcellulose (sometimes referred to as component (C)). The pharmaceutical composition of the present invention will be described in detail below.

[0012] (A) Ethyl aminobenzoate Ethyl aminobenzoate is a known local anesthetic also referred to as ethyl 4-aminobenzoate, benzocaine, etc.

[0013] In the pharmaceutical composition of the present invention, the content of component (A) is not particularly limited and may be appropriately set according to the degree of local anesthetic action to be imparted to the pharmaceutical composition, the dosage form and use 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 can be mentioned.

[0014] (B) Quaternary ammonium salts The quaternary ammonium salt used in the present invention may have a bactericidal action and may be pharmaceutically acceptable, and its type is not particularly limited. Examples include cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, decalinium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, methylbenzethonium chloride, lauroylcolaminomethylpyridinium chloride, etc.

[0015] These quaternary ammonium salts may be used alone or in combination of two or more.

[0016] Among these quaternary ammonium salts, from the viewpoint of more effectively suppressing yellowing due to light exposure, preferably cetylpyridinium chloride, benzalkonium chloride, and benzethonium chloride, and more preferably cetylpyridinium chloride can be mentioned.

[0017] In the pharmaceutical composition of the present invention, the content of 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 dosage form and use of the pharmaceutical composition, etc. For example, 0.05 to 1% by weight, preferably 0.1 to 0.5% by weight, more preferably 0.3 to 0.5% by weight can be mentioned.

[0018] 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). For example, per 100 parts by weight of component (A), 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.

[0019] (C) Polyhydric alcohols, monoterpenes, polyvinylpyrrolidone, and / or hydroxyethylcellulose In the pharmaceutical composition of the present invention, as component (C), it contains polyhydric alcohol, monoterpene, polyvinylpyrrolidone, and / or hydroxyethylcellulose. By containing the said component (C), it becomes possible to suppress the yellowing that occurs when ethyl aminobenzoate and quaternary ammonium salt coexist and are exposed to light.

[0020] The type of polyhydric alcohol used as component (C) is not particularly limited as long as it is pharmaceutically acceptable. For example, dihydric alcohols such as 1,3-butylene glycol, ethylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, polyethylene glycol, etc.; trihydric alcohols such as glycerin, etc. These polyhydric alcohols may be used alone or in combination of two or more.

[0021] Among these polyhydric alcohols, from the viewpoint of more effectively suppressing the yellowing due to light exposure, propylene glycol and glycerin are preferably mentioned.

[0022] (C) The monoterpenes used as components are known components that have a structure containing two isoprene units in their molecule and have a cooling effect. The types of monoterpenes used as components are not particularly limited, as long as they are pharmaceutically acceptable, but examples include alcohol-based monoterpenes such as menthol, thymol, geraniol, linalool, borneol, cineole, and terpineol; aldehyde-based monoterpenes such as citral, citronellal, perillaldehyde, and safranal; and ketone-based monoterpenes such as camphor, menthone, carbomenthone, and ionone. If optical isomers exist, any of the d-isomer, l-isomer, or dl-isomer may be used. These monoterpenes may be used individually or in combination of two or more.

[0023] Furthermore, in this invention, monoterpenes may be used in the form of essential oils containing monoterpenes. Essential oils containing monoterpenes can be appropriately selected from known ones, but examples of essential oils containing menthol include peppermint oil, spearmint oil, and peppermint menthol. Note that the descriptions of monoterpene content and ratios in this specification are values ​​converted to the amount of monoterpenes contained in the essential oil when using essential oils containing monoterpenes.

[0024] Among these monoterpenes, alcohol-based monoterpenes are preferred, more preferably menthol, and particularly preferably l-menthol, from the viewpoint of more effectively suppressing yellowing due to light exposure.

[0025] The polyvinylpyrrolidone used as component (C) is a water-soluble polymer compound formed by the polymerization of N-vinyl-2-pyrrolidone. The weight-average molecular weight of the polyvinylpyrrolidone used as component (C) is not particularly limited, but for example, it is about 5,000 to 3 million, more preferably about 40,000 to 3 million. Here, the weight-average molecular weight of polyvinylpyrrolidone refers to the value measured by gel filtration chromatography / multi-angle light scattering photometer (GPC / MALLS). The K value (viscosity property value) of polyvinylpyrrolidone is not particularly limited, but a value of about 10 to 120 can be preferably used. Furthermore, in this invention, commercially available polyvinylpyrrolidone can be used. Commercially available polyvinylpyrrolidone products include "iFact K-30PH" manufactured by Daiichi Kogyo Seiyaku Co., Ltd., "Polyvinylpyrrolidone K-30," "Polyvinylpyrrolidone K-85," and "Polyvinylpyrrolidone K-90" manufactured by Nippon Shokubai Co., Ltd., and "PVP K-90" manufactured by ISP Japan.

[0026] (C) The hydroxyethylcellulose used as component (C) is a cellulose derivative obtained by adding ethylene oxide to cellulose to improve its water solubility. The average number of moles of ethylene oxide added, the average molecular weight, etc. of the hydroxyethylcellulose used as component (C) are not particularly limited and can be any that is commonly used in the pharmaceutical field. For example, a viscosity of 500 mPa·s or more, preferably 500 to 50000 mPa·s, is used in a 2.0 wt% aqueous solution (20°C). Here, the viscosity is measured using a B-type viscometer "TOKI SANGYO VISCOMETER TVB-10" (Toki Sangyo Co., Ltd.) In the present invention, the value is measured appropriately using a rotor: M3 or M4 (rotation speed: 12-30 rpm, time: 1 min, unit: mPa·s) depending on the viscosity to be measured. Furthermore, in this invention, commercially available hydroxyethylcellulose can be used. Specifically, commercially available hydroxyethylcellulose products include "HEC CF-V", "HEC CF-W", "HEC CF-X", "HEC CF-Y", "HEC AH-15F", "HEC AV-15F", "HEC AW-15F", and "HEC SW-25F" from Sumitomo Seika Co., Ltd., "HEC Daicel SP500", "HEC Daicel SP600", "HEC Daicel SP850", and "HEC Daicel SP900" from Daicel Finechem Co., Ltd., and "NATROSOL 250HX" from Ashland, Inc.

[0027] In the pharmaceutical composition of the present invention, one of the following may be selected as component (C): polyhydric alcohol, monoterpene, polyvinylpyrrolidone, and hydroxyethylcellulose, or two or more may be used in combination.

[0028] From the viewpoint of more effectively suppressing yellowing due to light exposure, the (C) component is preferably a combination of a polyhydric alcohol and polyvinylpyrrolidone, and more preferably a combination of propylene glycol and polyvinylpyrrolidone.

[0029] (C) When polyhydric alcohol and polyvinylpyrrolidone are used in combination as components, there are no particular restrictions on their ratio, but from the viewpoint of more effectively suppressing yellowing due to light exposure, a ratio of 0.1 to 20 parts by weight, preferably 0.5 to 10 parts by weight, and more preferably 0.5 to 5 parts by weight of polyvinylpyrrolidone per 100 parts by weight of polyhydric alcohol is recommended.

[0030] In the pharmaceutical composition of the present invention, the content of component (C) can be appropriately set according to the type of component (C) used, the formulation form and use of the pharmaceutical composition, etc., but for example, the total amount of component (C) can be 0.01 to 80% by weight, preferably 0.05 to 70% by weight, and more preferably 0.1 to 65% by weight.

[0031] More specifically, the following ranges are given for the content of each type of component (C): When using polyhydric alcohols : 1-80% by weight, preferably 5-60% by weight. • When using a dihydric alcohol as the polyhydric alcohol: More preferably 1 to 60% by weight, particularly preferably 1 to 50% by weight, and most preferably 5 to 40% by weight. • When using a trihydric alcohol as the polyhydric alcohol: More preferably 10-60% by weight, particularly preferably 30-60% by weight, and most preferably 30-50% by weight. When using monoterpenes 0.01 to 3% by weight, preferably 0.05 to 1% by weight, more preferably 0.1 to 1% by weight. When using polyvinylpyrrolidone : 0.05 to 3% by weight, preferably 0.1 to 1% by weight, more preferably 0.5 to 1% by weight. When using hydroxyethylcellulose : 0.05 to 3% by weight, preferably 0.1 to 1% by weight, more preferably 0.5 to 1% by weight.

[0032] 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). For example, per 100 parts by weight of component (A), component (C) may be 10 to 20,000 parts by weight, preferably 15 to 18,000 parts by weight.

[0033] More specifically, the following ranges are given for the ratio of each type of component (C) to 100 parts by weight of component (A): When using polyhydric alcohols The total amount is 1,500 to 20,000 parts by weight, preferably 3,000 to 18,000 parts by weight. When using a dihydric alcohol as the polyhydric alcohol: more preferably 1,500 to 18,000 parts by weight in total, particularly preferably 3,000 to 18,000 parts by weight, and most preferably 5,000 to 18,000 parts by weight. When using a trihydric alcohol as the polyhydric alcohol: more preferably 2,000 to 18,000 parts by weight in total, particularly preferably 5,000 to 18,000 parts by weight, and most preferably 8,000 to 18,000 parts by weight. When using monoterpenes The total amount is 15 to 500 parts by weight, preferably 15 to 400 parts by weight, and more preferably 15 to 350 parts by weight. When using polyvinylpyrrolidone The total amount is 10 to 500 parts by weight, preferably 20 to 400 parts by weight, and more preferably 50 to 350 parts by weight. When using hydroxyethylcellulose The total amount is 30 to 500 parts by weight, preferably 50 to 500 parts by weight, and more preferably 50 to 400 parts by weight.

[0034] Lower alcohol The pharmaceutical composition of the present invention may optionally contain a lower alcohol to stably dissolve ethyl aminobenzoate.

[0035] The type of lower alcohol used in this invention is not particularly limited, as long as it is pharmaceutically acceptable, but examples include lower alcohols having 2 to 6 carbon atoms, such as ethanol, propanol, butanol, pentanol, hexanol, and isopropanol. Among these lower alcohols, ethanol is preferred.

[0036] These lower alcohols may be used individually or in combination of two or more.

[0037] When a lower alcohol is included in the pharmaceutical composition of the present invention, the amount is not particularly limited, but for example, it is 0.5 to 20% by weight, preferably 1 to 10% by weight, and more preferably 5 to 10% by weight.

[0038] water A preferred embodiment of the pharmaceutical composition of the present invention is one that contains water (i.e., an aqueous formulation). In the prior art, when ethyl aminobenzoate and quaternary ammonium salts are present together in the presence of water, yellowing due to light exposure tends to occur significantly. However, in the present invention, even when water is present, such yellowing can be effectively suppressed.

[0039] When the pharmaceutical composition of the present invention is made into an aqueous formulation, the water content is not particularly limited and can be set appropriately depending on the formulation form and use of the pharmaceutical composition, but for example, 1 to 80% by weight, preferably 5 to 60% by weight, and more preferably 10 to 50% by weight are given.

[0040] Other ingredients The pharmaceutical composition of the present invention may contain, in addition to the components described above, other pharmacological components as needed. Examples of such pharmacological components include antihistamines (diphenhydramine, diphenhydramine hydrochloride, etc.), local anesthetics other than ethyl aminobenzoate (procaine, tetracaine, bupipacaine, mepipacaine, chloroprocaine, propalacaine, meprilcaine or salts thereof, orthocaine, oxethazaine, oxypolyentoxydecane, belladonna extract, percaminate, tesitdecitin, lidocaine, etc.), and bactericides other than quaternary ammonium salts (iodine, povidone-iodine). Ingredients include: dipotassium iodide, chlorhexidine gluconate, acrinol, etc.; anti-inflammatory agents (dipotassium glycyrrhizinate, glycyrrhetinic acid, indomethacin, felbinac, diclofenac sodium, loxoprofen sodium, etc.); skin protectants (collodion, castor oil, etc.); blood circulation promoting ingredients (nonyl vanillylamide, benzyl nicotinate, capsaicin, chili pepper extract, etc.); vitamins (vitamin A, etc.); mucopolysaccharides (chondroitin sulfate sodium, glucosamine, etc.). Examples include:

[0041] Furthermore, the pharmaceutical composition of the present invention may contain base materials and additives other than those mentioned above, as necessary, in order to obtain a desired formulation. Such base materials and additives are not particularly limited to the extent that they are pharmaceutically acceptable, but examples include oils (olive oil, safflower oil, soybean oil, camellia oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, peanut oil, lard, squalane, fish oil, etc.), mineral oils (liquid paraffin, paraffin, gelling hydrocarbons, petrolatum, etc.), 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.), Oily bases such as 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, and silicone oils (dimethylpolysiloxane, cyclic silicone, etc.);Polyoxyethylene alkyl ethers 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-decyltetradecyl ether, POE (10-50 mol) polyoxypropylene (2-30 mol) cetyl ether, phosphates and phosphates of these (such as POE cetyl ether sodium phosphate), POE (20-60 mol) sorbitan monooleate, and POE (10-60 mol) sorbitan monoisostearate POE (10-80 mol) glyceryl monoisostearate, POE (10-30 mol) glyceryl monostearate, 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 esters (glyceryl monostearate, etc.), hydrogenated soybean phospholipids, hydrogenated lanolin alcohol, and other surfactants;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-cineole, citronellal, farnesol, etc.), coloring agents (tar dyes (Brown No. 201, Blue No. 201, Yellow No. 4, Yellow No. 403, etc.), cocoa pigment, chlorophyll, aluminum oxide, etc.), viscosity modifiers (sodium alginate, ethylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, xanthan gum, carrageenan, carboxyvinyl polymer, sodium polyacrylate, etc.), pH adjusters (phosphoric acid, hydrochloric acid, citric acid, quer Additives include sodium phosphate, succinic acid, tartaric acid, sodium hydroxide, potassium hydroxide, triethanolamine, triisopropanolamine, etc.; humectants (dl-pyrrolidone carboxylate sodium solution, D-sorbitol solution, macrogol, etc.); stabilizers (dibutylhydroxytoluene, butylhydroxyanisole, sodium edetate, sodium metaphosphate, L-arginine, L-aspartic acid, DL-alanine, glycine, sodium erythorbate, propyl gallate, sodium sulfite, sulfur dioxide, chlorogenic acid, catechin, rosemary extract, etc.); antioxidants; UV absorbers; chelating agents; adhesives; buffers; solubilizers; preservatives; and other additives.

[0042] Formulation 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 preferably it is a liquid or semi-solid aqueous formulation.

[0043] Furthermore, the pharmaceutical composition of the present invention may be a topical drug, a drug applied to mucous membranes, or an oral drug. Specific examples of topical drugs include gels, creams, lotions, emulsions, liquids, patches, aerosols, ointments, and packs. Specific examples of drugs applied to mucous membranes include gels, creams, lotions, emulsions, liquids, and ointments. Specific examples of oral drugs include liquids and jellies. These formulations can be prepared by compounding them using additives appropriate to the formulation, in accordance with known methods described in the General Provisions for Formulations of the Seventeenth Revised Japanese Pharmacopoeia, etc.

[0044] Among these formulation forms, preferred examples include topical skin medications and mucosal application medications such as gels, creams, lotions, emulsions, and liquids.

[0045] 2. Method for suppressing yellowing Furthermore, the present invention provides a method for suppressing yellowing caused by light exposure of a pharmaceutical composition comprising (A) ethyl aminobenzoate and (B) a quaternary ammonium salt, characterized in that the pharmaceutical composition is blended with (C) at least one selected from the group consisting of polyhydric alcohols, monoterpenes, polyvinylpyrrolidone, and hydroxyethylcellulose.

[0046] In the yellowing suppression method, the types and amounts of (A) to (C) used, the types and amounts of other ingredients included, and the formulation form of the pharmaceutical composition are the same as in the case of "1. Pharmaceutical Composition" described above. [Examples]

[0047] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0048] Test example 1. Preparation of pharmaceutical compositions The pharmaceutical compositions (topical skin drugs, liquid formulations) shown in Tables 1 and 2 were prepared. Specifically, predetermined amounts of ethyl aminobenzoate and l-menthol were dissolved in ethanol, and then added to water along with other components and mixed to obtain the pharmaceutical compositions (topical skin drugs, liquid formulations).

[0049] 2. Evaluation of formulation stability under light exposure Each pharmaceutical composition was placed in a screw-cap tube (a transparent glass container with a diameter of 24 mm and a height of 50 mm) and left to stand for 96 hours in a growth chamber set to 12,000 lx·hr and 25°C under fluorescent light irradiation. After that, the screw-cap tube was inverted and mixed 2-3 times, and the appearance of the pharmaceutical composition was visually observed. The stability of the formulation under light exposure was evaluated according to the following criteria. <Evaluation Criteria for Formulation Stability under Light Exposure> ◎: No yellowing was observed at all, and there are absolutely no problems with practical use. ○: A very slight yellowing is observed, but it does not pose a problem for practical use. △: Obvious yellowing is present, making it unsuitable for practical use. ×: Significant yellowing was observed, making it unsuitable for practical use.

[0050] 3.Results The results obtained are shown in Tables 1 and 2. Pharmaceutical compositions containing only ethyl aminobenzoate showed no yellowing whatsoever upon exposure to light (Reference Example 1). However, when ethyl aminobenzoate was present in combination with cetylpyridinium chloride, significant yellowing was observed upon exposure to light (Comparative Example 1). In contrast, when ethyl aminobenzoate and cetylpyridinium chloride were present together with one or more of the following: glycerin, propylene glycol, menthol, polyvinylpyrrolidone, and hydroxyethylcellulose, the yellowing due to light exposure was significantly improved (Examples 1-22). In particular, among the pharmaceutical compositions that were evaluated as having excellent formulation stability upon light exposure, those containing a combination of ethyl aminobenzoate, cetylpyridinium chloride, polyhydric alcohol (especially propylene glycol), and polyvinylpyrrolidone showed remarkably superior formulation stability.

[0051] [Table 1]

[0052] [Table 2]

[0053] Prescription examples The pharmaceutical compositions (medicines for oral mucosal application) shown in Table 3 were prepared. The formulation stability of the obtained pharmaceutical compositions was evaluated by exposure to light using the same method as in the above-mentioned test examples, and no yellowing was observed in any of them.

[0054] [Table 3]

Claims

1. A pharmaceutical composition containing (A) ethyl aminobenzoate, (B) a quaternary ammonium salt, and (C) hydroxyethylcellulose.

2. The pharmaceutical composition according to claim 1, wherein the (B) component is cetylpyridinium chloride.

3. The pharmaceutical composition according to claim 1 or 2, which is a topical drug or a drug applied to mucous membranes.

4. A method for suppressing yellowing caused by light exposure of a pharmaceutical composition containing ethyl aminobenzoate and a quaternary ammonium salt, The pharmaceutical composition contains (A) ethyl aminobenzoate and (B) a quaternary ammonium salt, along with (C) hydroxyethyl cellulose. A method for suppressing yellowing of the aforementioned pharmaceutical composition caused by light exposure.

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