JP2018108954A - Pharmaceutical composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a pharmaceutical preparation technique in which a pharmaceutical composition containing ethyl aminobenzoate and quaternary ammonium salt can suppress yellowing generated by light exposure, and be equipped with excellent pharmaceutical preparation stability.SOLUTION: A pharmaceutical composition, which is produced by blending one type or more of polyhydric alcohol, monoterpene, polyvinyl pyrrolidone, and hydroxyethyl cellulose together with ethyl aminobenzoate and quaternary ammonium salt, suppresses yellowing generated by light exposure, and can be equipped with excellent pharmaceutical preparation stability.SELECTED DRAWING: None

Description

  The present invention relates to a pharmaceutical composition having excellent formulation stability in which yellowing caused by exposure to light is suppressed while containing ethyl aminobenzoate and a quaternary ammonium salt.

  Ethyl aminobenzoate is known as a local anesthetic and is widely used to relieve local itching and pain in mucous membranes and skin. Conventionally, pharmaceutical formulations containing ethyl aminobenzoate have also been formulated. Various studies have been made. For example, Patent Document 1 reports that a local anesthetic composition containing a basic local anesthetic such as ethyl aminobenzoate and a hydrochloride thereof can have both rapid action and sustainability of local anesthetic action. Yes.

  In addition, quaternary ammonium salts such as cetylpyridinium chloride and benzalkonium chloride are known as bactericides and are widely used in various pharmaceuticals, etc., and pharmaceutical compositions containing quaternary ammonium salts conventionally Various studies have also been made on the 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 an external pharmaceutical composition characterized by the above can realize a stable preparation with suppressed crystal formation.

  In recent years, pharmaceutical compositions are required to have multi-functionality, and pharmaceutical formulations using a combination of a local anesthetic and a bactericide have been developed. However, in order to put the pharmaceutical composition into practical use, it is necessary to give sufficient consideration not only to the functionality but also to the stability of the preparation. In the prior art, a pharmaceutical composition containing ethyl aminobenzoate and a quaternary ammonium salt is used. At present, sufficient studies have not been made on the stability of pharmaceutical products.

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

  The present inventor has studied to put a pharmaceutical composition containing ethyl aminobenzoate and a quaternary ammonium salt into practical use. As a result, the composition for external use turns yellow (yellowing) when exposed to light, and is good. 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 pharmaceutical technology that can suppress yellowing caused by light exposure and has excellent pharmaceutical stability in a pharmaceutical composition containing ethyl aminobenzoate and a quaternary ammonium salt. is there.

  The present inventor conducted intensive studies to solve the above-mentioned problems. As a result, together with ethyl aminobenzoate and quaternary ammonium salt, one or more of polyhydric alcohol, monoterpene, polyvinyl pyrrolidone, and hydroxyethyl cellulose were used. It has been found that a pharmaceutical composition formulated in combination can suppress yellowing caused by light exposure and can have excellent formulation stability. The present invention has been completed by further studies based on this finding.

That is, this invention provides the invention of the aspect hung up below.
Item 1. A pharmaceutical composition comprising (A) ethyl aminobenzoate, (B) a quaternary ammonium salt, and (C) at least one selected from the group consisting of a polyhydric alcohol, monoterpene, polyvinylpyrrolidone, and hydroxyethylcellulose. object.
Item 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.
Item 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 topical drug or a mucosal drug.
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 comprises (A) ethyl aminobenzoate, and (B) quaternary ammonium salt, and at least one selected from the group consisting of (C) polyhydric alcohol, monoterpene, polyvinylpyrrolidone, and hydroxyethylcellulose. Blending,
A method for suppressing yellowing caused by light exposure of the pharmaceutical composition.

  According to the pharmaceutical composition of the present invention, even when ethyl aminobenzoate and a quaternary ammonium salt coexist, yellowing caused by light exposure 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 (A) component), quaternary ammonium salt (sometimes referred to as (B) component), and polyhydric alcohol. And at least one selected from the group consisting of monoterpene, polyvinyl pyrrolidone, and hydroxyethyl cellulose (sometimes referred to as (C) component). Hereinafter, the pharmaceutical composition of the present invention will be described in detail.

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

  In the pharmaceutical composition of the present invention, the content of the component (A) is not particularly limited, and is appropriately set depending on the degree of local anesthetic action to be imparted to the pharmaceutical composition, the formulation form and use of the pharmaceutical composition, etc. For example, it may be 0.1 to 5% by weight, preferably 0.3 to 2% by weight, and 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. Examples thereof include cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, decalinium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, methylbenzethonium chloride, lauroylcoraminoformylmethylpyridinium chloride and the like.

  These quaternary ammonium salts may be used individually by 1 type, and may be used in combination of 2 or more type.

  Among these quaternary ammonium salts, cetylpyridinium chloride, benzalkonium chloride, and benzethonium chloride are preferable, and cetylpyridinium chloride is more preferable, from the viewpoint of more effectively suppressing yellowing due to light exposure. It is 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 use of the pharmaceutical composition, etc. For example, it may be 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 the component (B) to the component (A) is determined according to the contents of the component (A) and the component (B), but for example, 100 parts by weight of the component (A) The component (B) is 10 to 300 parts by weight, preferably 50 to 200 parts by weight, more preferably 50 to 150 parts by weight.

(C) Polyhydric alcohol, monoterpene, polyvinyl pyrrolidone, and / or hydroxyethyl cellulose In the pharmaceutical composition of the present invention, the component (C) contains polyhydric alcohol, monoterpene, polyvinyl pyrrolidone, and / or hydroxyethyl cellulose. . By including the component (C), it is possible to suppress yellowing that occurs when ethyl aminobenzoate and a quaternary ammonium salt coexist with light exposure.

  The type of polyhydric alcohol used as component (C) is not particularly limited as long as it is pharmaceutically acceptable. For example, 1,3-butylene glycol, ethylene glycol, propylene glycol, isoprene glycol, diethylene glycol , Dihydric alcohols such as dipropylene glycol and polyethylene glycol; and trihydric alcohols such as glycerin. These polyhydric alcohols may be used individually by 1 type, and may be used in combination of 2 or more type.

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

  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 the component (C) is not particularly limited as long as it is pharmaceutically acceptable.For example, alcohols such as menthol, thymol, geraniol, linalool, borneol, cineol, terpineol, etc. Monoterpenes; Aldehyde monoterpenes such as citral, citronellal, perylaldehyde, safranal; Ketone monoterpenes such as camphor, menthone, carbomenton, and yonon. These monoterpenes may be any of d-form, l-form, and dl-form when optical isomers are present. These monoterpenes may be used individually by 1 type, and may be used in combination of 2 or more type.

  Moreover, in this invention, you may use in the state of the essential oil containing a monoterpene as a monoterpene. The essential oil containing monoterpene can be appropriately selected from known ones and used, for example, as essential oil containing menthol, mint oil, peppermint oil, spearmint oil and the like can be mentioned. In addition, the description regarding content and ratio of a monoterpene in this specification is the value converted into the amount of monoterpenes contained in the said essential oil, when using the essential oil containing a monoterpene.

  Among these monoterpenes, from the viewpoint of more effectively suppressing yellowing due to light exposure, alcohol monoterpenes are preferable, menthol is more preferable, and l-menthol is particularly preferable.

  The polyvinyl pyrrolidone used as the component (C) is a water-soluble polymer compound obtained by polymerizing N-vinyl-2-pyrrolidone. The weight average molecular weight of the polyvinylpyrrolidone used as the component (C) is not particularly limited, but 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 a value of about 10 to 120 can be preferably used. Moreover, in this invention, a commercial item can be used for polyvinylpyrrolidone. As a commercially available product of polyvinylpyrrolidone, specifically, “Iftact K-30PH” manufactured by Daiichi Kogyo Seiyaku Co., Ltd., “Polyvinylpyrrolidone K-30”, “Polyvinylpyrrolidone K-85” manufactured by Nippon Shokubai Co., Ltd., “Polyvinylpyrrolidone K-90”, “PVP K-90” manufactured by IS Japan, and the like can be mentioned.

  Hydroxyethyl cellulose used as the component (C) is a cellulose derivative whose water solubility is improved by adding ethylene oxide to cellulose. The average added mole number of ethylene oxide of hydroxyethyl cellulose used as the component (C), the average molecular weight and the like are not particularly limited and may be any one that is usually 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% aqueous solution (20 ° C.). Here, the said viscosity is a rotor: M3 or M4 (rotation speed: 12-30 rpm, time) according to the viscosity to be measured in a B-type viscometer “TOKI SANGYO VISCOMETER TVB-10” (manufactured by Toki Sangyo Co., Ltd.). : 1 min, unit: mPa · s). In the present invention, a commercially available product can be used as hydroxyethyl cellulose. Specific examples of commercially available 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, Inc., Examples thereof include “HEC Daicel SP900” and “NATROSOL 250HX” manufactured by Ashland.

  In the pharmaceutical composition of the present invention, as the component (C), one kind selected from polyhydric alcohol, monoterpene, polyvinylpyrrolidone, and hydroxyethyl cellulose may be used, or two or more kinds may be used in combination. May be.

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

  When the polyhydric alcohol and polyvinylpyrrolidone are used in combination as the component (C), these ratios are not particularly limited, but from the viewpoint of more effectively suppressing yellowing due to light exposure, the polyhydric alcohol. The ratio by which polyvinylpyrrolidone is 0.1-20 weight part normally per 100 weight part, Preferably it is 0.5-10 weight part, More preferably, 0.5-5 weight part is mentioned.

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

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

  In the pharmaceutical composition of the present invention, the ratio of the component (C) to the component (A) is determined according to the contents of the component (A) and the component (C). For example, 100 parts by weight of the component (A) The component (C) is 10 to 20000 parts by weight, preferably 15 to 18000 parts by weight.

More specifically, examples of the ratio of each type of component (C) to 100 parts by weight of component (A) include the following ranges:
When using a polyhydric alcohol : The total amount is 1500-20000 parts by weight, preferably 3000-18000 parts by weight.
-When using a dihydric alcohol as a polyhydric alcohol: In a total amount, More preferably, it is 1500-18000 weight part, Especially preferably, it is 3000-18000 weight part, Most preferably, it is 5000-18000 weight part.
When a trihydric alcohol is used as the polyhydric alcohol: The total amount is more preferably 2000-18000 parts by weight, particularly preferably 5000-18000 parts by weight, and most preferably 8000-18000 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 using polyvinylpyrrolidone : The total amount is 10 to 500 parts by weight, preferably 20 to 400 parts by weight, more preferably 50 to 350 parts by weight.
When using hydroxyethyl cellulose : The total amount is 30 to 500 parts by weight, preferably 50 to 500 parts by weight, more preferably 50 to 400 parts by weight.

Lower alcohol The pharmaceutical composition of the present invention may contain a lower alcohol, if necessary, 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. For example, ethanol, propanol, butanol, pentanol, hexanol, isopropanol and the like having 2 to 6 carbon atoms are used. A lower alcohol is mentioned. Among these lower alcohols, ethanol is preferable.

  These lower alcohols may be used individually by 1 type, and may be used in combination of 2 or more type.

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

As a preferred embodiment of the pharmaceutical composition of the water present invention, to contain water (i.e., aqueous formulations) are exemplified. In the prior art, when ethyl aminobenzoate and a quaternary ammonium salt coexist in the presence of water, yellowing due to light exposure tends to be noticeable, but in the present invention, water is included. However, the yellowing can be effectively suppressed.

  When the pharmaceutical composition of the present invention is made into an aqueous preparation, the content of water is not particularly limited, and may be set as appropriate according to the preparation form and use 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 Components The pharmaceutical composition of the present invention may contain other pharmacological components as necessary in addition to the components described above. Examples of such pharmacological components include antihistamines (diphenhydramine, diphenhydramine hydrochloride, etc.), local anesthetics other than ethyl aminobenzoate (procaine, tetracaine, bupipacaine, mepipacaine, chloroprocaine, proparacaine, meprilucaine or salts thereof, orthocaine , Oxesazein, oxypolyentoxydecane, funnel extract, percamine ase, tesit decite, lidocaine, etc., bactericides other than quaternary ammonium salts (iodine, popidone iodine, potassium iodide, chlorhexidine gluconate, acrinol, etc.), anti-inflammatory agents (glycyrrhizin) Dipotassium acid, glycyrrhetinic acid, indomethacin, felbinac, diclofenac sodium, loxoprofen sodium, etc.), skin protectant (Colodion) Castor oil, etc.), blood circulation promotion component (nonylic acid vanillylamide, nicotinic acid benzyl ester, capsaicin, capsicum extract, and the like), vitamins (vitamin A, etc.), mucopolysaccharides (sodium chondroitin sulfate, glucosamine, etc.) and the like.

  Moreover, in order to make the pharmaceutical composition of this invention into a desired formulation form, base materials and additives other than the component mentioned above may be contained as needed. Such bases and additives are not particularly limited as long as they are pharmaceutically acceptable. For example, 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 oil (liquid paraffin, paraffin, gelled hydrocarbon, petrolatum, etc.), waxes / waxes (honey beeswax, carnauba wax, candelilla wax, ceresin, rice wax, Microcrystalline wax, etc.), ester oil (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, tri-2-ethylhexanoic acid glyceryl, 2-ethylhexanoic acid cetyl, silicone oil (dimethylpolysiloxane, cyclic silicone, etc.) Agents: POE (10-50 mol) phytosterol ether, POE (10-50 mol) dihydrocholesterol ether, POE (10-50 mol) 2-octane Ludodecyl ether, POE (10-50 mol) decyl tetradecyl 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 to 30 mol) 2-decyl tetradecyl ether, POE (10 to 50 mol) polyoxypropylene (2 to 30 mol) cetyl ether, and other polyoxyethylene alkyl ethers, phosphoric acid- Phosphate (such as POE cetyl ether sodium phosphate), 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 to 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 to 100), polysorbate (20 to 85), glycerin fatty acid ester (such as glyceryl monostearate), hydrogenated soybean Surfactants such as phospholipids and hydrogenated lanolin alcohol; refreshing agents (menthol, camphor, borneol, mint) , Mint oil, etc.), preservatives (methylparaben, propylparaben, benzoic acid, sodium benzoate, sorbic acid, etc.), flavoring agents (citral, 1,8-shionale, citronellal, farnesol, etc.), coloring agents (tar pigment ( Brown 201, blue 201, yellow 4, yellow 403, etc.), cacao pigment, chlorophyll, aluminum oxide, etc.), thickener (sodium alginate, ethyl cellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, xanthan gum, carrageenan, carboxy Vinyl polymer, sodium polyacrylate, etc.), pH adjuster (phosphoric acid, hydrochloric acid, citric acid, sodium citrate, succinic acid, tartaric acid, sodium hydroxide, potassium hydroxide, triethanolamine, triisopropanol ), Wetting agents (dl-pyrrolidone carboxylate 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.), antioxidant, UV absorber, chelating agent, adhesive, Additives such as buffers, solubilizers, solubilizers, preservatives and the like can be mentioned.

Formulation Form The dosage form of the pharmaceutical composition of the present invention is not particularly limited and may be any of liquid, semi-solid (gel, ointment, paste, etc.), solid, etc. A liquid or semi-solid form which is an aqueous preparation can be mentioned.

  In addition, the pharmaceutical composition of the present invention may be any of an external medicine, a mucosa application medicine, or an internal medicine. Specific examples of external medicines include gels, creams, lotions, emulsions, solutions, patches, aerosols, ointments, packs and the like. Specific examples of the mucosa-applied pharmaceutical include gels, creams, lotions, emulsions, liquids, ointments and the like. Specific examples of internal medicines include solutions and jellies. These preparation forms can be prepared by formulating with additives according to the preparation form in accordance with known methods described in the 17th revised Japanese Pharmacopoeia General Rules for Preparations.

  Among these preparation forms, preferably, external pharmaceutical preparations for skin such as gels, creams, lotions, emulsions, liquids, etc., and pharmaceuticals applied to mucous membranes are used.

2. Yellowing suppression method Furthermore, the present invention provides a method of suppressing yellowing caused by exposure to light of a pharmaceutical composition comprising (A) ethylamino benzoate, and (B) a quaternary ammonium salt, the pharmaceutical compositions (C) At least 1 sort (s) selected from the group which consists of a polyhydric alcohol, a monoterpene, polyvinylpyrrolidone, and a hydroxyethyl cellulose is mix | blended with a thing.

  In the yellowing suppression method, the types and contents of (A) to (C) to be used, the types and contents of other components to be blended, the formulation form of the pharmaceutical composition, etc. are described in “1. This is the same as in the case of “thing”.

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

Test Example 1 Preparation of pharmaceutical composition Pharmaceutical compositions (skin external preparations and liquids) shown in Tables 1 and 2 were prepared. Specifically, after dissolving predetermined amounts of ethyl aminobenzoate and l-menthol in ethanol, and adding them to water together with other components, the pharmaceutical composition (medicinal preparation for skin use, liquid) is prepared. Obtained.

2. Evaluation of formulation stability by light exposure Each pharmaceutical composition was placed in a screw tube (glass transparent container having a diameter of 24 mm and a height of 50 mm) and 96 hours in a growth chamber set to 12000 lx · hr and 25 ° C. under irradiation with a fluorescent lamp. Left to stand. Thereafter, the screw tube was mixed by inversion 2-3 times, the appearance of the pharmaceutical composition was visually observed, and the preparation stability by light exposure was evaluated according to the following criteria.
<Evaluation criteria for formulation stability by light exposure>
(Double-circle): Yellowing is not recognized at all and there is no problem in practical use.
○: Although slight yellowing is observed, there is no problem in practical use.
Δ: Obvious yellowing is observed, which is not suitable for practical use.
X: Remarkable yellowing was observed, which is not suitable for practical use.

3. Results The results obtained are shown in Tables 1 and 2. The pharmaceutical composition in which only ethyl aminobenzoate was dissolved did not show any yellowing even when exposed to light (Reference Example 1). However, when ethyl aminobenzoate was allowed to coexist with cetylpyridinium chloride, significant yellowing was observed by light exposure (Comparative Example 1). On the other hand, when one or more of glycerin, propylene glycol, menthol, polyvinyl pyrrolidone, and hydroxyethyl cellulose were coexisted with ethyl aminobenzoate and cetylpyridinium chloride, yellowing due to light exposure could be greatly improved ( Examples 1-22). In particular, among pharmaceutical compositions evaluated as ◎ for formulation stability due to light exposure, when containing a combination of ethyl aminobenzoate, cetylpyridinium chloride, polyhydric alcohol (particularly propylene glycol), and polyvinylpyrrolidone, Remarkably remarkable formulation stability was observed.

Formulation Example A pharmaceutical composition (oral mucosa-applied drug) shown in Table 3 was prepared. About the obtained pharmaceutical composition, when the formulation stability by light exposure was evaluated by the method similar to the said test example, yellowing was not recognized by all.

Claims (7)

  A pharmaceutical composition comprising (A) ethyl aminobenzoate, (B) a quaternary ammonium salt, and (C) at least one selected from the group consisting of a polyhydric alcohol, monoterpene, polyvinylpyrrolidone, and hydroxyethylcellulose. object.   The pharmaceutical composition according to claim 1, wherein the component (B) is cetylpyridinium chloride.   The pharmaceutical composition according to claim 1 or 2, wherein the polyhydric alcohol is propylene glycol and / or glycerin.   The pharmaceutical composition according to any one of claims 1 to 3, wherein the monoterpene is menthol.   The pharmaceutical composition according to any one of claims 1 to 4, comprising a polyhydric alcohol and polyvinylpyrrolidone as the component (C).   The pharmaceutical composition according to any one of claims 1 to 5, which is a topical medicine or a mucosa-applied medicine. A method for suppressing yellowing caused by light exposure of a pharmaceutical composition comprising ethyl aminobenzoate and a quaternary ammonium salt,
The pharmaceutical composition comprises (A) ethyl aminobenzoate, and (B) quaternary ammonium salt, and at least one selected from the group consisting of (C) polyhydric alcohol, monoterpene, polyvinylpyrrolidone, and hydroxyethylcellulose. Blending,
A method for suppressing yellowing caused by light exposure of the pharmaceutical composition.