JP2009196934A - Pharmaceutical formulation containing new quinolone based antibacterial agent and emulsion base - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new pharmaceutical formulation which can be locally administrated to an ear cavity, a nasal cavity, an oral cavity, etc., is held in an administration part over a long time, and has a good drug releasability. <P>SOLUTION: The pharmaceutical formulation, in which a new quinolone based antibacterial agent is blended with an emulsion base, is held in the administration part for a long time and shows a good drug releasability. The pharmaceutical formulation is effective in treating of an infection disease in a local part, and an effect of a medicine with a few gap between individuals is expectable. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a novel pharmaceutical composition comprising a new quinolone antibacterial agent and an emulsion base. Furthermore, the present invention relates to a topical therapeutic agent comprising the pharmaceutical composition, preferably a sinusitis therapeutic agent.

  As preparations for topical administration, there are ointments, gel preparations, liquids and the like (Patent Document 1, Non-Patent Documents 1 and 2). Topical administration has the advantage that the drug in the affected area can be maintained at a high concentration, and an excellent therapeutic effect can be expected, and further, side effects that are a concern during systemic administration can be avoided. In fact, in the field of otolaryngology, topical administration of antibacterial drugs and antibiotics into the ear cavity and nasal cavity using ear drops or nebulizers has an effect on otitis media, sinusitis, etc., while side effects are observed. Not reported (Non-patent Document 1).

  However, when the liquid is administered through ear drops or a nebulizer, the medicinal solution flows out of the administration site and cannot be expected to have a sustained effect, and the effect is greatly affected by the state of the administration site. It has been known. In addition, there is a foreign body excretion movement such as cilia movement in the nasal cavity and sinus cavity, and there is a concern that the preparation is discharged from the administration site.

In fact, levofloxacin gel sustained-release preparation was administered to middle ear bacterial infection model animals and the antibacterial effect was examined. However, the bactericidal effect was not observed in individuals with insufficient. In other words, it has been pointed out that the effect of individual gels varies due to the residence time of the sustained-release preparation (Non-Patent Document 2).
In order to solve these problems, a preparation having better local retention and drug release is desired.
JP 2006-176461 A Otolaryngology, 1990, Vol. 36, Supplement No. 3, p. 523-536 Drug Delivery System, 2006, Vol. 21, No. 5, p. 523-528

  The present invention relates to a novel pharmaceutical composition comprising a new quinolone antibacterial agent and an emulsion base that can be locally administered to the ear cavity, nasal cavity, oral cavity and the like and retained at the administration site for a long time, and further, the pharmaceutical composition A local therapeutic agent, preferably a sinusitis therapeutic agent.

  As a result of intensive studies, the present inventors have found that the emulsion base has sufficient adhesion and local retention in mucous membranes such as the ear cavity and nasal cavity. Furthermore, since it was newly found that a pharmaceutical composition comprising the above-mentioned base and a new quinolone antibacterial agent stays at the administration site for a long time and shows a good drug release, these pharmaceutical compositions are locally infected. It is useful for treatment of infectious diseases, especially for sinusitis, and can be expected to have a medicinal effect with little difference between individuals.

That is, the present invention
(1) A pharmaceutical composition comprising a new quinolone antibacterial agent and an emulsion base,
(2) The pharmaceutical composition according to the above (1), wherein the new quinolone antibacterial agent is any one of levofloxacin, ofloxacin or sitafloxacin,
(3) The pharmaceutical composition according to any one of (1) or (2) above, wherein the emulsion base is an emulsion base containing an oleaginous substance, a surfactant, a humectant, a stabilizer and water. ,
(4) The emulsion base is (a) one or a combination of two or more components selected from the group consisting of white petrolatum, paraffin, liquid paraffin, squalane, cetanol, white beeswax, stearyl alcohol and stearic acid, (b) mono 1 or 2 or more components selected from the group consisting of glyceryl stearate, polyoxyethylene cetyl ether, polyoxyl 40 stearate, sulbitane sesquioleate and Raul macrogol, (c) glycerin, propylene glycol, sorbitol solution And a component of one or more combinations selected from the group consisting of 1,3-butylene glycol, (d) a group consisting of methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate and butyl paraoxybenzoate Component of one or more combinations selected, and (e) above are emulsion base comprising water (1) or a pharmaceutical composition according to any one of (2),
(5) The above (1) or (1), wherein the emulsion base is an emulsion base containing squalene, cetanol, stearyl alcohol, glyceryl monostearate, polyoxyethylene cetyl ether, ethyl paraoxybenzoate, propyl paraoxybenzoate and water The pharmaceutical composition according to any one of (2),
(6) The above (1), wherein the emulsion base is an emulsion base containing white petrolatum, cetanol, honey beeswax, sulbitane sesquioleate, lauromacrogol, ethyl paraoxybenzoate, butyl paraoxybenzoate and water. Or the pharmaceutical composition according to any one of (2),
(7) The emulsion base described in (3) to (6) above, further comprising one or two or more combinations of components selected from the group consisting of cellulose derivatives, polyvinyl polymer compounds and polysaccharides (3) The pharmaceutical composition according to any one of (6),
(8) The pharmaceutical composition according to any one of (3) to (6) above, further comprising xanthan gum in the emulsion base according to (3) to (6) above,
(9) The present invention relates to a therapeutic agent for sinusitis comprising the pharmaceutical composition according to any one of (1) to (8) above.

  The pharmaceutical composition of the present invention has good adhesion, retention and drug eluting properties, as will be apparent from the following test examples. Therefore, even when administered to mucous membranes such as nasal cavity, ear cavity and oral cavity, It is considered that local infections can be treated without any variation in the effects.

  In addition, since the pharmaceutical composition of the present invention is a semi-solid preparation, it can be easily administered to a sinus having a complicated structure by the method described below.

  From the above, the pharmaceutical composition of the present invention can be suitably used for the treatment of local infectious diseases including the ear cavity, nasal cavity and oral cavity.

  The new quinolone antibacterial agent according to the present invention is one of a series of synthetic antibacterial agents, and is a drug that acts bactericidally by inhibiting DNA gyrase. Although the new quinolone antibacterial agent according to the present invention is not particularly limited, examples of drugs approved in Japan include levofloxacin (trade name: Cravit), ofloxacin (trade name: Tarivid), sitafloxacin (trade name: Gracebit), Examples include profloxacin and gatifloxacin.

  The new quinolone antibacterial agent according to the present invention is preferably levofloxacin, ofloxacin or sitafloxacin, and particularly preferably levofloxacin.

  The emulsion base according to the present invention is a base prepared by emulsifying an oily substance and water in the presence of a surfactant. Depending on the emulsified state, there are an oil-in-water type (O / W type) and a water-in-oil type (W / O type). The emulsion base according to the present invention is either an oil-in-water type (O / W type) or a water-in-oil type (W / O type) as long as it has good local retention and drug release properties. Also good. If desired, a humectant, a preservative, and an adhesive polymer added to an emulsion base are also included in the present invention.

  The oily substance is not particularly limited as long as it is usually used for an emulsion base, but hydrocarbons such as white petrolatum, paraffin, yellow petrolatum, liquid paraffin, squalane, cetanol, ceresin, etc .; Waxes such as beeswax, lanolin; avocado oil, olive oil, cacao oil, sesame oil, soybean oil, castor oil, macadamia nut oil, mink oil, egg yolk oil, beef tallow, pork oil; lauric acid, stearic acid, myristic acid, palmitic Examples include higher fatty acids such as acid, oleic acid, and linoleic acid; fatty acid higher alcohols such as stearyl alcohol, oleyl alcohol, lauryl alcohol, cetyl alcohol, and lanolin alcohol.

  Examples of the surfactant include an anionic surfactant, a cationic surfactant, an amphoteric surfactant, and a nonionic surfactant. Nonionic surfactants are classified into ester type, ether type, ester / ether type and others according to their structures. The surfactant used in the emulsion base of the present invention is not particularly limited as long as it is usually used in an emulsion base, but a nonionic surfactant is preferred from the viewpoint of stability. Preferred are glyceryl monostearate, polyoxyethylene cetyl ether, polyoxyl 40 stearate, sulbitane sesquioleate, Raul macrogol, isopropyl myristate and isopropyl palmitate, and particularly preferred examples include glyceryl monostearate, Mention may be made of polyoxyethylene cetyl ether, polyoxyl 40 stearate, sulbitane sesquioleate and Raul macrogol.

  The humectant is not particularly limited as long as it is usually used for an emulsion base, but glycerin, propylene glycol, sorbitol solution and 1,3-butylene glycol, polyethylene glycol, sodium dl-pyrrolidonecarboxylate, lactic acid Examples thereof include sodium and sodium hyaluronate.

  Preservatives are not particularly limited as long as they are usually used in emulsion bases, but paraoxybenzoates (methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate and butyl paraoxybenzoate) Benzalkonium chloride, benzethonium chloride, citric acid, sodium citrate, paraoxybenzoic acid, boric acid and the like, preferably paraoxybenzoic acid esters, particularly preferably ethyl paraoxybenzoate and / or paraoxybenzoic acid Propyl.

  The adhesive polymer is not particularly limited as long as it improves local retention and has good drug release, but a hydrophilic adhesive polymer is preferable, for example, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose. , Cellulose derivatives such as hydroxypropylmethylcellulose, sodium carboxymethylcellulose, carboxyvinyl polymer, polyvinylpyrrolidone, copolymers of vinylpyrrolidone and vinyl acetate, polyvinyl polymer compounds such as copolymers of acrylic acid ester and vinyl acetate, Polysaccharides such as hyaluronic acid, hyaluronic acid salt such as sodium hyaluronate, chondroitin sulfate salt such as sodium chondroitin sulfate, polyethylene oxide, xanthan gum, carrageenan, guar gum, agar It can be exemplified Biagomu, pectin, sodium alginate and the like.

  In the pharmaceutical composition of the present invention, a preparation containing xanthan gum is preferable because it exhibits good adhesion and local retention. Furthermore, it is possible to adjust the local residence time and drug release by adjusting the amount of xanthan gum added. The amount of xanthan gum added is preferably 0.5 to 5% by weight, more preferably 1 to 5% by weight.

  When the pharmaceutical composition of the present invention containing xanthan gum which is one embodiment of the present invention is administered locally to the mucous membrane or the like, the surface area on which the preparation adheres to the mucous membrane increases because the xanthan gum absorbs surrounding water and swells. Therefore, it is considered that the drug release is promoted, and it is suitable as a topical preparation.

  Although it will not specifically limit if it is the quality which can be used for a pharmaceutical as water, Purified water is preferable.

  The emulsion base of the pharmaceutical composition of the present invention comprises 5 to 30% by weight of an oleaginous substance, 5 to 20% by weight of a surfactant, 1 to 10% by weight of a humectant, and 0.01 to 0 of a preservative. It is preferable to contain 1% by weight.

  More preferably, the emulsion contains 5 to 15% by weight of an oily substance, 8 to 15% by weight of a surfactant, 2 to 10% by weight of a humectant, and 0.02 to 0.08% by weight of a preservative. It is a base.

  The content of the new quinolone antibacterial agent of the present invention may be appropriately selected in view of the antibacterial activity of the drug, but is preferably 0.1 to 5.0% by weight, more preferably 0.2 to 3.0. % By weight, particularly preferably 0.5 to 1.0% by weight.

  As an emulsion base particularly suitable for the present invention, an oil-in-water emulsion base containing squalene, cetanol, stearyl alcohol, glyceryl monostearate, polyoxyethylene cetyl ether, ethyl paraoxybenzoate, propyl paraoxybenzoate and water Can be illustrated.

  As a particularly preferred example of a pharmaceutical composition comprising a new quinolone antibacterial agent and an oil-in-water emulsion base which is one embodiment of the present invention, there can be mentioned formulations having the compositions shown in Examples 1 and 2 below. Since these preparations have stronger adhesion than the gel sustained-release preparations (Test Example 1) and exhibit the same drug dissolution properties (Test Example 2), they have excellent drug effects with little individual difference.

  Furthermore, as an emulsion base particularly suitable for the present invention, water-in-oil type containing white petrolatum, cetanol, white beeswax, sulbitane sesquioleate, lauromacrogol, ethyl paraoxybenzoate, butyl paraoxybenzoate and water. An emulsion base can be exemplified.

  A particularly preferred example of a pharmaceutical composition comprising a new quinolone antibacterial agent and a water-in-oil emulsion base, which is an embodiment of the present invention, is a preparation having the composition shown in Example 3 below.

  A general method for producing the pharmaceutical composition of the present invention is as follows. The oily substance and the surfactant are heated and dissolved and stirred on a water bath, and kept at 70 to 80 ° C., preferably 70 to 75 ° C., to obtain an oil phase. A water phase component obtained by adding a preservative, a humectant, an adhesive polymer, etc., to purified water, if necessary, is heated and dissolved at 75 to 80 ° C. The pharmaceutical composition of the present invention can be obtained by adding the aqueous phase component to the oil phase component, stirring to make an emulsion, and then stirring until cooled and solidified.

  Since the pharmaceutical composition of the present invention is a semi-solid preparation, it can be administered by applying it to a body surface such as the skin, the oral cavity, the lips, the eyes, the nasal cavity, the mucous tissue such as the vagina. In addition, when the pharmaceutical composition is administered to the sinuses, the pharmaceutical composition is filled into a syringe, a tube is attached to the tip of the syringe, the tube tip is introduced from the nasal cavity into the sinus, and the pharmaceutical composition in the syringe is placed. Can be administered by infusion.

  Since the pharmaceutical composition of the present invention contains a new quinolone antibiotic and is suitable for external use, superficial skin infection, deep skin infection, chronic pyoderma, acne (with purulent inflammation) , Secondary infection such as trauma / burn and surgical wound, perianal abscess, pharyngeal / laryngitis, tonsillitis (including peritonsillitis, peritonsillar abscess), lacrimal cystitis, hordeolum, pleurisy, otitis externa It can be used for the treatment of infectious diseases such as sinusitis, purulent salivary glanditis, periodontitis, and peri-crownitis.

  The dosage of the pharmaceutical composition of the present invention to a patient can be appropriately determined according to the patient's sex, age, symptoms, drug type, administration site, administration method, number of administrations, administration timing, etc. That's fine.

  Hereinafter, the present invention will be described in more detail with reference to examples and test examples, but the present invention is not limited thereto.

(Example 1) Xanthan gum non-added cream
Ingredient (g)
Levofloxacin hemihydrate 1.02
(1.00 as levofloxacin)
Squalane 9.00
Cetanol 3.00
Stearyl alcohol 2.00
Glycerol monostearate (P-100) 5.00
Polyoxyethylene cetyl ether (BC-7) 1.00
1,3-butylene glycol 5.00
Ethyl paraoxybenzoate 0.03
Propyl paraoxybenzoate 0.02
Polyoxyethylene cetyl ether (BC-20) 4.00
Purified water 70.0

Cetanol, stearyl alcohol, glyceryl monostearate and polyoxyethylene cetyl ether (BC-7) were added to squalane and heated to 75 ° C. to melt (oil phase). Separately, after adding polyoxyethylene cetyl ether (BC-20), ethyl paraoxybenzoate and propyl paraoxybenzoate to 1,3-butylene glycol and heating and melting at 80 ° C., add purified water and levofloxacin , Heated to 80 ° C. (aqueous phase). The aqueous phase was added to the oil phase and emulsified with vigorous stirring for 3 minutes. The heating was stopped, and stirring was continued until the temperature reached room temperature to obtain a levofloxacin-containing cream containing no xanthan gum.

(Example 2) Xanthan gum added cream
Ingredient (g)
Levofloxacin hemihydrate 1.02
(1.00 as levofloxacin)
Squalane 9.00
Cetanol 3.00
Stearyl alcohol 2.00
Glycerol monostearate (P-100) 5.00
Polyoxyethylene cetyl ether (BC-7) 1.00
1,3-butylene glycol 5.00
Ethyl paraoxybenzoate 0.03
Propyl paraoxybenzoate 0.02
Polyoxyethylene cetyl ether (BC-20) 4.00
Xanthan gum (Echo gum-T) 1.00
Purified water 69.0

Cetanol, stearyl alcohol, glyceryl monostearate and polyoxyethylene cetyl ether (BC-7) were added to squalane, heated to 75 ° C. and melted (oil phase). Separately, polyoxyethylene cetyl ether (BC-20), ethyl paraoxybenzoate and propyl paraoxybenzoate were added to 1,3-butylene glycol and heated and melted at 80 ° C., and then purified water and the main agent were added. Warmed to 80 ° C. (aqueous phase). The aqueous phase was added to the oil phase and emulsified with vigorous stirring for 3 minutes. After the heating was stopped and the adhesive polymer was added, stirring was continued until the temperature reached room temperature to obtain a levofloxacin-containing cream containing 1% xanthan gum. Similarly, creams containing 0.5% by weight, 2% by weight, and 5% by weight of xanthan gum were prepared and used for the test.

(Example 3) Water-absorbing ointment formulation
Ingredient (g)
Levofloxacin hemihydrate 1.02
(1.00 as levofloxacin)
Water-absorbing ointment ^* (Japanese Pharmacopoeia) 99.0
*: Prescription of water-absorbing ointment (100g)
Ingredient (g)
White petrolatum 40.0
Cetanol 10.0
Sara honey bees 5.0
Sulbitane sesquioleate 5.0
Lauro Macrogol 0.5
Ethyl paraoxybenzoate 0.1
Butyl paraoxybenzoate 0.1
Purified water 39.3

Levofloxacin was added to a melt obtained by heating the water-absorbing ointment to 80 ° C., dispersed, and then cooled to room temperature with stirring to obtain a water-absorbing ointment formulation.

(Example 4) White petrolatum formulation
Ingredient (g)
Levofloxacin hemihydrate 1.02
(1.00 as levofloxacin)
White petrolatum (Japanese Pharmacopoeia) 99.0

Levofloxacin was added to a white petrolatum heated to 80 ° C. and melted, and the mixture was dispersed and then cooled to room temperature with stirring to obtain a white petrolatum preparation.

(Example 5) Gel sustained-release preparation
Ingredient (g)
Levofloxacin hemihydrate 1.02
(1.00 as levofloxacin)
Hydroxypropylcellulose 69.0
Macrogol 6000 15.0
Talc 6.00

After putting levofloxacin, hydroxypropylcellulose, macrogol 6000 and talc into a fluidized bed granulator (multiplex MP-01 type; manufactured by POWREC Co., Ltd.), set the intake air temperature to 85 ° C, and granulate while heating and flowing. The mixture was cooled and sieved using a No. 16 sieve to obtain a granulated product.

(Example 6) Polyethylene oxide-added gel sustained-release preparation
Ingredient (g)
Levofloxacin hemihydrate 1.02
(1.00 as levofloxacin)
Hydroxypropyl cellulose 66.0
Polyethylene oxide (PEO) 3.00
Macrogol 6000 15.0
Talc 6.00

Put levofloxacin, hydroxypropylcellulose, polyethylene oxide, macrogol 6000 and talc into a fluidized bed granulator (multiplex MP-01 type; manufactured by POWREC Co., Ltd.), set the intake air temperature to 85 ° C, and heat and flow After granulation, the mixture was cooled and sieved using a No. 16 sieve to obtain a granulated product. Similarly, a levofloxacin-containing gel sustained-release preparation containing 10% by weight and 30% by weight of polyethylene oxide was prepared and used for the test.

(Test Example 1) In vitro adhesion evaluation The in vitro adhesion of each preparation was tested according to the following procedure.
1. Preparation of gel plate 1 g and 2 g of agar and mucin were weighed out, 100 mL of phosphate buffer (pH 6.0) was added, and the mixture was dissolved by heating (the preparation amount was appropriately changed). This solution was cast in a petri dish (10 cm × 14 cm square type) and stored in a refrigerator for 3 hours.
2. Preparation of test solution Phosphate buffer solution: 550 mL of sodium hydroxide solution (0.2 mol / L) and water to 50 mL of potassium dihydrogen phosphate test solution (0.2 mol / L for pH 6.0 buffer solution) and 200 mL It was.
Potassium dihydrogen phosphate test solution: 27.22 g of potassium dihydrogen phosphate (0.2 mol / L) was dissolved in water to make 1000 mL.

3. Evaluation Method Various preparations (0.1 mL) prepared in Examples 1, 2, 5 and 6 were placed in the center of the agar / mucin plate, allowed to stand for 2 minutes, and then the agar / mucin plate was set in a disintegration tester. The gel plate was immersed in a phosphate buffer (pH 6.0) heated to 37 ° C., and shaking was started as in the disintegration test.

  The time when the preparation was peeled from the agar / mucin plate was evaluated as the Residence time. The results are shown in FIGS. It was confirmed that the cream has good adhesiveness and exhibits further excellent adhesiveness by the addition of xanthan gum.

(Test Example 2) In Vitro Dissolution Evaluation Each formulation obtained in Examples 1, 2, 3, 5 and 6 was tested according to the dissolution test method of the Japanese Pharmacopoeia. 100 mg of each preparation was placed on an enhancer cell, and a dialysis membrane (Seamless Cellulose Tubing; manufactured by Viscose Companies, Inc.) previously cut to an appropriate size was placed thereon, and the cell was set. An enhancer cell (FIG. 3) was placed in a fully automatic dissolution tester (NTR-6100A, manufactured by Toyama Sangyo Co., Ltd.), and the test was carried out in a pH 6.0 phosphate buffer solution at 37 ° C. with a 20 paddle method. Specifically, the drug concentration in the test solution was measured by the UV method (cell length: 10 mm, measurement wavelength: 287 nm), and the elution amount was determined. The results are shown in FIG. The cream showed dissolution equivalent to or better than the gel sustained-release preparation, and the xanthan gum-added cream showed rapid dissolution.

(Test Example 3) In vivo retention evaluation Surgery was performed in the following manner, and the adhesion state of each preparation in the chinchilla ridge peak was confirmed by MRI imaging.
1. Under ether anesthesia, hair removal was performed around the milk ridge peak.
2. A 7-8 mm incision was made in the vicinity of the top of the ridge of the milk ridge peak until a bone was visible in the longitudinal direction with a scalpel.
3. A hole was made in the bone with a pointed tip or the like, and the hole was widened with an ophthalmic scissors.
4). Each of the preparations of Examples 1 to 6 was administered such that the dosage of levofloxacin was 1 mg / head.
5. The incision was sutured and the operation was completed.
6). Nembutal was administered intraperitoneally, and the chinchilla was fixed to an imaging table, and MRI imaging (MRI measuring machine: BIOSPEC 47/40, manufactured by BRUKER) was performed.

  Even after 7 days, good retention of the cream was observed, and the cream added with xanthan gum was confirmed to have a wide range of retention. A part of the measurement results is shown in FIG.

  As is clear from the above examples, the pharmaceutical composition of the present invention is excellent in local retention and drug release properties and is useful as a topical preparation, and the pharmaceutical composition can be used as a pharmaceutical composition for treating sinusitis. .

: In vitro adhesion evaluation result of gel sustained-release preparation. The horizontal axis indicates the amount of polyethylene oxide (PEO) added to each formulation. The change in adhesion due to the addition amount of PEO was weak. : It is the in vitro adhesion evaluation result of a cream. The horizontal axis indicates the amount of xanthan gum (XG) added to each formulation. It was confirmed that good adhesion was exhibited by adding 0.5 to 5% by weight of XG. FIG. 2 is a drawing of a test system including an enhancer cell used in Test Example 1. FIG. : It is the figure which showed the result of the elution property evaluation of Test Example 1. Cream XG 0% (Example 1) and cream XG 5% (Example 2) showed the same dissolution properties as the gel prepared at the time of use (■, □ in the figure). In addition, it was confirmed that the water-absorbing ointment preparation gradually elutes. : Photographs showing the adhesion state of each preparation on the first day, 1 day and 7 days after administration. The left column is a gel sustained-release preparation containing 3% PEO, the center is a cream, the right column is a water-absorbing ointment formulation and a white petrolatum formulation. In the photograph of the center row cream, the left arrow is the cream with XG 5% by weight added, and the right arrow is the cream with no XG added. In the right column photograph, the left arrow is a water-absorbing ointment preparation, and the right arrow is a white petrolatum preparation.

Claims (9)

A pharmaceutical composition comprising a new quinolone antibacterial agent and an emulsion base. The pharmaceutical composition according to claim 1, wherein the new quinolone antibacterial agent is any one of levofloxacin, ofloxacin or sitafloxacin. The pharmaceutical composition according to any one of claims 1 and 2, wherein the emulsion base is an emulsion base containing an oleaginous substance, a surfactant, a humectant, a stabilizer and water. The emulsion base is (a) one or a combination of two or more components selected from the group consisting of white petrolatum, paraffin, liquid paraffin, squalane, cetanol, white beeswax, stearyl alcohol and stearic acid; (b) glyceryl monostearate 1 or a combination of two or more selected from the group consisting of polyoxyethylene cetyl ether, polyoxyl 40 stearate, sorbitan sesquioleate and Raul macrogol, (c) glycerin, propylene glycol, sorbitol solution and 1,3- 1 or 2 or more components selected from the group consisting of butylene glycol; (d) 1 or 2 selected from the group consisting of (d) methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate and butyl paraoxybenzoate Components of the combination of the above, and (e) an emulsion base comprising water, a pharmaceutical composition according to any one of claims 1 or 2. 3. The emulsion base according to claim 1, wherein the emulsion base is an emulsion base comprising squalene, cetanol, stearyl alcohol, glyceryl monostearate, polyoxyethylene cetyl ether, ethyl paraoxybenzoate, propyl paraoxybenzoate and water. 2. A pharmaceutical composition according to claim 1. The emulsion base of claim 1 or 2, wherein the emulsion base is white petrolatum, cetanol, white beeswax, sulbitane sesquioleate, lauromacrogol, ethyl paraoxybenzoate, butyl paraoxybenzoate and water. The pharmaceutical composition according to any one of the above. The emulsion base according to any one of claims 3 to 6, further comprising one or a combination of two or more components selected from the group consisting of cellulose derivatives, polyvinyl polymer compounds and polysaccharides. The pharmaceutical composition according to any one of the above. The pharmaceutical composition according to any one of claims 3 to 6, further comprising xanthan gum in the emulsion base according to claims 3 to 6. A therapeutic agent for sinusitis comprising the pharmaceutical composition according to any one of claims 1 to 8.