JP2003252800A - External composition for mucosa - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an external composition for mucosa, especially a composition for an ophthalmological and an otolaryngological use, expressing excellent antiseptic effect without compounding a conventional antiseptic and having high safety for an inflamed mucosa by increasing antiseptic efficacy of trometamol. <P>SOLUTION: The composition is characterized by containing trometamol and a terpenoid. The composition containing at least one selected from a group consisting of polyhydric alcohols, glycyrrhizins and berberines has more improved antiseptic effect. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a composition for external mucosa which has an excellent antiseptic effect, is highly safe for mucous membranes such as eyes and nose, and is excellent in application to allergic symptoms and various inflammations.

[0002]

2. Description of the Related Art Conventionally, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, sorbic acid, paraoxybenzoic acid ester, tiromesal, phenylethyl alcohol, alkylaminoethylglycine have been used as preservatives for external mucosal agents such as eye drops. It is used. Among them, cationic preservatives represented by benzalkonium chloride are most often used because they have a broad antibacterial spectrum and have a high antiseptic effect even in a small amount. Among the commercially available eye drops in Japan, 61.8% (60.5% of benzalkonium chloride and 1.3% of chlorhexidine gluconate) use cationic preservatives, which accounts for more than half ( Non-Patent Document 1).

However, it is known that the above-mentioned preservatives may cause irritation to mucous membranes, particularly ocular mucous membranes, and among them, cationic antiseptics are known to promote eye irritation. For example, if an eye drop containing benzalkonium chloride is instilled frequently, or if a person with a disorder of the cornea or a person with abnormal tear kinetics showing dry eye symptoms is instilled, side effects such as damage to the cornea Is said to occur (see Non-Patent Document 2), and there is concern about safety.

Such damage to the corneal epithelium is not limited to benzalkonium chloride, but is also applicable to other cationic antiseptics, paraoxybenzoates, etc. (see Non-Patent Documents 3 and 4). ).

Further, since the cationic preservative has a positive charge, it may interact with a compounding component having a negative charge to cause clouding. In this case, if the preservative to be used is used at a concentration lower than that normally used, the above-mentioned compounding contraindications may not occur, but the preservative efficacy, which is the original purpose, will be reduced, and therefore it will not actually be applied. It was difficult to do.

[0006] Therefore, various studies have been conducted on a method in which a cationic preservative whose use is limited depending on the drug to be blended is blended at a low concentration and the preservative effect is sufficiently exhibited. As such a method, for example, when the above-mentioned preservative is benzalkonium chloride, a method using a preservative other than this, a paraoxybenzoic acid ester and a chelating agent in combination (see Patent Document 1), or boric acid A method of combining ions (see Patent Document 2) has been proposed.

However, these proposals are concerned that they may cause problems such as eye irritation and allergies depending on the concentration of the preservative used in combination, and it is said that paraoxybenzoic acid esters are particularly corneal lesions. It can be said that there is a problem in safety from the fact that they are present. Therefore, a stable external ophthalmic preparation such as an ophthalmic preparation having a high antiseptic property and no irritation has been desired.

On the other hand, trometamol is a compound known as a buffer (Tris buffer) (see Non-Patent Document 5). In addition, in the ophthalmic composition, in addition to being described as a buffering agent, it is described as a stabilizer for a specific drug (see Patent Documents 3 and 4), and as an efficacy improving agent for fat-soluble vitamins (Patent Document 5). There is). Furthermore, Japanese Patent Application 2001
Japanese Patent No. 121619 (Patent Document 6) describes an ophthalmic composition for contact lenses containing trometamol as a preservative.

[0009]

[Patent Document 1] Japanese Patent Publication No. 7-5456

[Patent Document 2] Japanese Unexamined Patent Publication No. 10-130156

[Patent Document 3] JP-A-8-291065

[Patent Document 4] Japanese Patent Laid-Open No. 11-302162

[Patent Document 5] Japanese Patent Laid-Open No. 2002-104959

[Patent Document 6] Japanese Patent Application No. 2001-121619

[Non-Patent Document 1] Journal of Japan Contact Lens Society 35 p
238-241, 1993

[Non-patent document 2] Ophthalmology 31 p43-48 1989
Year, Ophthalmology 33 p533-538 1991

[Non-patent document 3] New ophthalmology 10 1909-1
Page 911 1993

[Non-patent document 4] Journal of Japan Contact Lens Society 35
238-241, 1993

[Non-Patent Document 5] 11th Revised Japanese Pharmacopoeia B-5
51, 1986

[0010]

DISCLOSURE OF THE INVENTION The present invention enhances the antiseptic effect of trometamol, exhibits an excellent antiseptic effect without the addition of conventionally used antiseptics, and is safe for mucous membranes inflamed. It is an object of the present invention to provide an external preparation for high mucosa, particularly an ophthalmic composition and an otolaryngological composition.

[0011]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that an aqueous solution containing trometamol and terpenoids has an excellent antiseptic effect. Furthermore, by adding one or more selected from polyhydric alcohols, glycyrrhizinic acid, and berberine to this aqueous solution, it was possible to further improve the antiseptic effect and to find that it has excellent safety against mucous membranes. The present invention has been completed.

That is, the present invention is a composition for external mucosa containing <1> trometamol and terpenoids. <2> The composition for external mucosa according to <1>, further containing at least one compound selected from the group consisting of polyhydric alcohols, glycyrrhizinic acids, and berberines. <3> The composition for external mucosa according to <1> or <2>, which further comprises a water-soluble polymer compound. <4> No preservative is contained, <1> to
The composition for external mucosa according to <3>. <5> The external mucosal agent composition according to <1> to <4>, which is a pharmaceutical composition for anti-inflammatory and / or anti-allergy. <6> The composition for external mucosa according to <1> to <5>, which is a composition for ophthalmology or otolaryngology. I will provide a.

The present invention further comprises <7> trometamol and terpenoids as an antiseptic composition for external preparation for mucosa. <8> A method for improving the antiseptic activity of trometamol, which comprises blending terpenoids. I will provide a.

[0014]

The present invention will be described in more detail below. The content of trometamol used in the present invention is preferably 0.1 to 5 g / 100 ml in the composition.
(Hereinafter, w / v%), more preferably 0.2 to 4 w / v
%, And more preferably 0.2 to 3 w / v%. Within this range, a good composition for external use of mucosa having a particularly high antiseptic property, an appropriate osmotic pressure and no irritation can be obtained.

The terpenoids used in the present invention enhance the antiseptic efficacy of trometamol. Terpenoids include terpene hydrocarbons, terpene alcohols, terpene aldehydes and terpene ketones. Also,
Depending on the carbon number, there are monoterpenes, sesquiterpenes, diterpenes, triterpenes and tetraterpenes, but monoterpenes are preferably used. Specific preferred terpenoids include monoterpenes and vitamins such as menthol (l-menthol, dl-menthol), camphor (dl-camphor, d-camphor), borneol (d-borneol, ryuno), geraniol, cineol and linalool. Examples include A (diterpene) and carotenoid (tetraterpene). As the terpenoids, a purified compound may be used or an essential oil containing terpenoids may be used. Examples of the essential oil containing terpenoids include eucalyptus oil, bergamot oil, fennel oil, rose oil, peppermint oil, peppermint oil, spearmint oil, and essential oil of dipterocarpaceous plant, rosmarinic oil, lavender oil and the like. Raru These terpenoids (including essential oils containing terpenoids) may be used alone or in combination of two or more.

The terpenoids are preferably contained in the composition in an amount of 0.0001 to 1 w / v%. More preferably 0.0005 to 0.2 w / v%, and even more preferably 0.00.
It is in the range of 001 to 0.1 w / v%. Within this range, a good external composition for mucosa that effectively improves the antiseptic effect of trometamol and is free of irritation can be obtained. Of the terpenoids, menthol, for example, is known to have a bactericidal and antiseptic action, but usually, in the above concentration range to be incorporated in a mucosal external preparation etc., effective bactericidal and antiseptic actions cannot be obtained. . However, when used together with trometamol, the antiseptic effect of trometamol can be significantly enhanced.

The polyhydric alcohol, glycyrrhizic acid and berberine in the present invention have the effect of further enhancing the antiseptic effect of the composition for external mucosa of the present invention.

The polyhydric alcohol used in the present invention is not particularly limited as long as it is a compound having a plurality of hydroxy groups, but glycerin, polyethylene glycol, propylene glycol, mannitol and glucose are preferable, and glycerin and propylene glycol are particularly preferable. The content of the polyhydric alcohol is 0.01 to 1 in the composition.
0 w / v% is preferable, and more preferably 0.01 to 5 w.
/ V%, particularly preferably 0.1 to 3 w / v%. Within this range, a particularly excellent antiseptic effect can be obtained, and a good external composition for mucosa having a good feeling in use can be obtained.

Among the polyhydric alcohols, for example, propylene glycol has a weak antifungal action, but its antiseptic effect is not sufficient. However, when used together with trometamol, it exerts a remarkable effect as an antiseptic agent.

The berberines used in the present invention include berberine chloride, berberine sulfate, etc. These can be used alone or in combination of two or more kinds. In the present invention, it is also possible to blend a plant containing the above-mentioned berberine, for example, crude drugs such as laurel, lauren powder, rye syrup, rye syrup powder and the like. The content of berberine chloride is 0.0001 to 0.1 w in the composition.
/ V% is preferable. More preferably 0.001-0.0
5 w / v%, particularly preferably 0.0005 to 0.02
It is 5 w / v%. Within this range, a particularly excellent antiseptic effect can be obtained, and a good external composition for mucosa having a good feeling in use can be obtained.

Glycyrrhizic acid in the present invention is preferably glycyrrhizinic acid, dipotassium glycyrrhizinate, tripotassium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, monoammonium glycyrrhizinate, diammonium glycyrrhizinate, and the like. Can be used alone or in combination of two or more. In addition, in the present invention, a plant or the like containing the above-mentioned glycyrrhizic acid, for example, a herbal medicine such as licorice, licorice extract or the like can be blended. The content of glycyrrhizinates is 0.01 to
2 w / v% is preferred. More preferably 0.05-1w
/ V%, particularly preferably 0.1 to 0.5 w / v%. Within this range, a particularly excellent antiseptic effect can be obtained, and a good external composition for mucosa having a good feeling in use can be obtained. In particular,
When the content is 0.1% or more, in addition to the above effects, the absorbability of the active ingredient is improved and a particularly excellent drug effect is obtained, which is preferable.

The external preparation for mucosa of the present invention can be made into an excellent non-mucosal pharmaceutical preparation without irritation by adding various active ingredients to be added to the preparation for mucosa. In particular, it is useful as a drug for anti-inflammatory and anti-allergy, and preferable active ingredients include anti-allergic drug, anti-histamine drug, and vasoconstrictor drug.

The antiallergic agent is cromoglycic acid or a salt thereof (sodium cromoglycate, etc.), amlexanox, tranilast, pemirolast or a salt thereof (pemirolast potassium, etc.), ketotifen or a salt thereof (ketotifen fumarate, etc.), and preferably Is sodium cromoglycate or tranilast. These may be commercially available products. The preferred content of the antiallergic drug varies depending on the type, but is 0.01 to 10 w / v%
It is preferably in the range of. Specifically, for example, the content of cromoglycic acid or its salt is 0.1 to 5 w / v% (more preferably 0.5 to 3 w / v%), and the content of amlexanox is 0.01 to 7 w / v% (more preferably Is 0.05
~ 5w / v%), the content of tranilast is 0.02-10
w / v% (more preferably 0.05 to 5 w / v%), the content of pemirolast or its salt is 0.01 to 5 w / v% (more preferably 0.05 to 3 w / v%), ketotifen or its The salt content is 0.01 to 8 w / v% (more preferably 0.05 to 5 w / v%). Amounts within this range are highly safe for mucous membranes and have an excellent antiallergic effect.

Examples of the antihistamine include chlorpheniramine maleate, diphenhydramine hydrochloride, diphenhydramine, clemastine fumarate, mequitazine, iproheptin hydrochloride, isothipendyl hydrochloride, and the like. Maleine, which is excellent in safety and effect, is mentioned. Chlorpheniramine acid and diphenhydramine hydrochloride are preferable, and chlorpheniramine maleate, which is excellent in stability, is more preferable. The preferred content of the antihistamine drug varies depending on its type, but is usually 0.005 to
1 w / v%, more preferably 0.01 to 0.5 w /
v%. This range is preferable from the viewpoints of sufficient antihistamine action and safety against mucous membranes.

Examples of the vasoconstrictor include naphazoline hydrochloride, tetrahydrozoline hydrochloride, naphazoline nitrate,
Tetrahydrozoline nitrate, methylephedrine hydrochloride, phenylephrine hydrochloride, methoxamine hydrochloride, epinephrine,
Examples thereof include ephedrine hydrochloride, but naphazoline hydrochloride and tetrahydrozoline hydrochloride, which are excellent in stability, are preferable. The content of the vasoconstrictor varies depending on its type, but is usually 0.001 to 1 w / v%, preferably 0.005 to
It is 0.5 w / v%. This range is preferable from the viewpoint of sufficient antihypertensive action and safety for mucous membranes.

Other pharmaceutically active ingredients include, for example, anti-inflammatory / astringent agents (neostigmine methylsulfate, ε-aminocaproic acid, allantoin, zinc sulfate, zinc lactate,
Lysozyme chloride, methyl salicylate, tranexamic acid,
Azulene sulfonate, etc.), water-soluble vitamins (flavin adenine dinucleotide sodium, pyridoxine hydrochloride, cyanocobalamin), vitamins (vitamins A (eg retinol acetate, retinol palmitate)), vitamins E (tocopherol acetate (eg,
D-α-tocopherol acetate), active vitamin B2,
Vitamin B6, Vitamin B12), amino acids (potassium L-aspartate, magnesium L-aspartate, aminoethylsulfonic acid, sodium chondroitin sulfate, etc.), sulfa drugs, fungicides (sulfamethoxazole, sulfamethoxazole sodium) , Sulfisoxazole, sulfisomidine sodium, isopropylmethylphenol, hinokitiol, sulfur, etc.), etc.
Local anesthetics (lidocaine, lidocaine hydrochloride, procaine hydrochloride, dibucaine hydrochloride, etc.) can be mentioned. The effective ingredients can be appropriately mixed in effective amounts.

The composition for external mucosa of the present invention preferably contains a thickening agent in addition to the above components. It is possible to improve the retention of the drug by the thickening agent and to maintain the medicinal effect without blending a large amount of the active ingredient (that is, without irritation by excessive drug). Examples of the thickening agent include polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl polymer compounds such as carboxyvinyl polymer, methylcellulose, hydroxypropylmethylcellulose,
Examples thereof include cellulose-based polymer compounds such as ethyl cellulose, and polysaccharides such as sodium hyaluronate and sodium chondroitin sulfate. Among the above, the polyvinyl-based polymer compound and the cellulose-based polymer compound are preferable because they are particularly excellent in drug retention and have a good feeling in use.

Examples of the cellulose-based polymer compound include crystalline cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, hydroxyethyl methyl cellulose and the like. In the above,
A cellulose ether in which a part of hydrogen atoms of the hydroxyl group is substituted with a methyl group, an ethyl group, a hydroxypropyl group or a hydroxyethyl group is preferable. Particularly preferred cellulose-based polymer compounds are methylcellulose and hydroxypropylpyrmethylcellulose. They have a particularly strong specific interaction force with mucin of mucosa, which significantly improves the effectiveness of the drug. A preferable alkoxyl group substitution rate of the hydroxyl group of the cellulose ether is 10 to 45%, and particularly 15 to 45%.
45% is preferable. Further, the interaction force of the cellulosic polymer with mucin becomes more effective when the weight average molecular weight is 5 × 10 ⁴ or more, and particularly 5 × 10 ⁴ to 1
× 10 ⁶ , 5 × 10 ^{4 to} 5 × 10 ⁵ are preferable. The content of the cellulose-based polymer compound is preferably 0.01 to 10 w / v% in the composition, and particularly preferably 0.05 to 5
Blend in the range of w / v%. When the content is within this range, the retention of the drug becomes particularly good.

The vinyl polymer used in the present invention includes polyvinyl alcohol, polyvinylpyrrolidone,
Examples thereof include carboxyvinyl polymer and polyvinyl methyl ether, and polyvinyl alcohol and polyvinyl pyrrolidone are preferable. Polyvinyl alcohol has a saponification degree of 78 mol% or more, preferably 78 to 96 mo
1%, particularly preferably 85 to 90 mol% is used. The weight average molecular weight of the preferable vinyl polymer is 10,000 to 300,000, and more preferably 20,000 to 150,000. The content of the vinyl polymer is preferably 0.02 to 0.02 in the composition.
20 w / v%, more preferably 0.05 to 10 w / v
%, Particularly preferably 0.1 to 10 w / v%. When the content is within this range, the retention of the drug becomes particularly good.

The viscosity of the composition at 20 ° C. is adjusted to 3 mPa · s to 20 mPa · s, preferably 3 mPa · s to 15 mPa · s using the above thickening agent.
With a viscosity in this range, the eye drop containing the polymer compound of the present invention is easy to come out of the eye drop container, and is not sticky and has good usability.

In addition to the above components, the composition for external mucosa of the present invention contains various additives such as a pH adjusting agent, a buffering agent, a solubilizing agent, an isotonicity adjusting agent and a stabilizing agent. It can be contained within a range that does not impair the effect.

As the pH adjuster, sodium hydroxide,
Examples thereof include potassium hydroxide and hydrochloric acid. Examples of the buffering agent include boric acid or a salt thereof (borax etc.), citric acid or a salt thereof (sodium citrate etc.), phosphoric acid or a salt thereof (sodium monohydrogen phosphate etc.), tartaric acid or a salt thereof (tartaric acid). Sodium etc.), gluconic acid or its salt (sodium gluconate etc.), acetic acid or its salt (sodium acetate etc.), carbonic acid or its salt (sodium hydrogen carbonate etc.), various amino acids (ε-aminocaproic acid, potassium aspartate, Aminoethyl sulfonic acid, glutamic acid, sodium glutamate, etc.) or a combination thereof. Preferred buffering agents are boric acid or salts thereof (borax etc.), phosphoric acid or salts thereof (sodium monohydrogen phosphate etc.) and ε-aminocaproic acid. Particularly preferably,
Boric acid or its salt is used. The content of the buffer is preferably 0.01 to 3 w / v% in the composition.

Examples of the solubilizing agent include polyoxyethylene (p = 60), polyoxyethylene higher fatty acid ester such as hydrogenated castor oil, and polyoxyethylene (p = 60).
20) Polyoxyethylene sorbitan higher fatty acid ester such as sorbitan monooleate. The content of these is 0.001 to 0.5 w / v in the composition.
%, Preferably 0.001-0.1 w / v%
Is more preferable. From the viewpoint of irritation, it is preferable to reduce the amount of these surfactants to be blended as much as possible, and it is particularly preferable not to blend them. Examples of the isotonicity agent include sodium chloride, potassium chloride and the like. Examples of the stabilizer include sodium edetate, cyclodextrin, sulfite, citric acid or a salt thereof, dibutylhydroxytoluene, and the like. If it is sodium edetate, 0.001 to 0.5 w / v% can be added to the composition, preferably 0.01 to 0.2 w / v.
% Range. Further, dibutylhydroxytoluene can be usually added in an amount of 0.001 to 0.1 w / v%, preferably 0.01 to 0.01 w / v%.

The pH of the preparation of the present invention is not particularly limited as long as it is within a pharmaceutically acceptable range, and it is usually in the range of pH 4 to 9, more preferably 5 to 8.5. Also,
When using glycyrrhizinic acid, it is preferable to set the pH to 4 to 6, particularly 4 to 5.5 because the drug absorbability is dramatically improved. In the composition of the present invention, a pH adjusting agent and a buffering agent are added as necessary so as to maintain the pH within the above range.

The osmotic pressure of the preparation of the present invention is not particularly limited as long as it is within a pharmaceutically acceptable range, and is usually 0.1 to 5
It is a pressure ratio, and more preferably adjusted to a pressure ratio of 0.2 to 2. The osmotic pressure can be adjusted with a tonicity agent as needed.

The composition for external mucosa of the present invention is described in the preservatives usually used for compositions for external mucosa such as benzalkonium chloride (Pharmaceutical Additives 2000 (edited by Japan Pharmaceutical Additives Association, Yakuji Nippo)). It can be used as a preservative-free composition for external mucosa which does not contain a preservative which has a precedent use for ophthalmology. More specifically, it can be applied as a good ophthalmic agent that does not cause irritation to eyes that are tired due to use of OA or wearing contact lenses, dry eyes, and allergic symptoms such as hay fever. Further, the application of the composition for external mucosa of the present invention is not particularly limited, and it is used as a medical eye drop or a general eye drop. Eye drops can be applied even when a soft contact lens or a hard contact lens is worn, and the composition can be used as an eye wash or a contact lens mounting solution. In particular, it is useful as a composition for soft contact lenses for which adsorption to soft contact lenses is a technical subject. Also,
It can also be used as an otolaryngological drug such as rhinitis.

That is, the composition for external mucosa of the present invention comprises: an external composition for anti-inflammatory and / or anti-allergy, an external composition for ophthalmology or an otolaryngology, a dry composition. It can be preferably used as an ophthalmic composition for improving eye and tired eye symptoms and an ophthalmic composition for soft contact lenses.

The method for producing the composition for external preparation for mucosa of the present invention is as follows:
It is not particularly limited. For example, it can be prepared as follows as a production example of eye drops. Trometamol is dissolved in about 80% by weight of purified water, and the pH is adjusted to about 7.3 with diluted hydrochloric acid. Further, each compounding component is added and dissolved, and then the pH is adjusted again to 7.3, and the mixture is aseptically filled in an eye drop container (15 mL) made of polyethylene terephthalate.

[0039]

The present invention will be described in more detail below with reference to examples, and the effects of the present invention will be clarified.

<Examples 1 and 2 and Comparative Examples 1 to 4> Table 1
An eye drop was prepared with the composition shown in (the compounding amount: g / 100 m
L), the following tests 1 and 2 were performed. <Test 1> Eye irritation test An eye drop having the formulation shown in Table 1 was prepared (blending amount: g / 100 m).
L), filled in a container, and published by Ministry of Health and Welfare Scientific Research Report (1945)
Preservative for eye drops in accordance with the short-term test method for mucous membrane irritation. The evaluation criteria are as follows. <Evaluation Criteria> ◎: Average score by Draize method is 0 or more and less than 2 points ○: 2 points or more and less than 4 points Δ: 4 points or more and less than 6 points ×: 6 points or more

<Test 2> Antiseptic efficacy test The antiseptic efficacy was carried out with reference to the Preservation Efficacy Test Method of the 14th Revised Japanese Pharmacopoeia and Reference Information, with some modifications. As test strains, the following 5 kinds of bacteria and fungi were used, and 10 ⁵ to 10 ⁶ cells were added per 1 mL of the samples of Examples and Comparative Examples, and the mixture was allowed to stand at 25 ° C. and inoculated with the bacteria after 1 day. After culturing 1 mL of each of the prepared solutions, the viable cell count was measured, and the residual rate (%) with respect to the inoculated cell count was calculated. Bacteria: Pseudomonas aeruginosa ATCC9027, Escherichia
coli ATCC8739, Staphylococcus aureus ATCC6538 Fungus: Candida albicans ATCC10231, Aspergillus nige
r ATCC16404

[0042]

[Table 1]

As is clear from the results shown in Table 1, Example 4 containing (A) trometamol and (B) terpenoids as borneol was Comparative Example 1 excluding the component (B).
Compared with the above, the antiseptic effect in a short period of one day was increased. Furthermore, in Examples 1 to 3 in which the eye drop composition of Example 4 was blended with (C) propylene glycol as the polyhydric alcohol, (D) dipotassium glycyrrhizinate as the glycyrrhizinates (E) berberine chloride as the berberines, and the like. The antiseptic effect was remarkably enhanced as compared with Example 4. Also,
It was shown that all of Examples 1 to 4 had no eye irritation and were highly safe.

<Examples 5 to 25> Eye drops having the compositions shown in Tables 2 to 5 (Examples 5 to 22) and eye washes (Examples 23 and 2)
4) and the contact mounting solution (Example 25) were prepared and evaluated in Experimental Examples 1 and 2, and good results were obtained in all cases.

[0045]

[Table 2]

[0046]

[Table 3]

[0047]

[Table 4]

[0048]

[Table 5]

<Pharmaceutical formulation for antiallergic> According to the composition shown in Table 6, an antiallergic eye drop was prepared by a conventional method. Five men with a history of allergies were panelists,
The degree of improvement and duration of itching when each eye drop was administered at the onset of allergy (itch) was investigated. Test Examples 1 and 2 in which glycyrrhizinic acid and hydroxypropylmethylcellulose were mixed showed better improvement in itchiness and persistence than Test Example 3 in which glycyrrhizinic acid was not mixed, and an excellent antiallergic pharmaceutical preparation was obtained. In addition, in each of the test examples, the evaluation of antiseptic property and irritation was good.

Evaluation Criteria for Improving Itching Immediately After Instillation ◎: Itching was reduced ○: Itching was slightly reduced Δ: Itching did not change ×: Itching slightly worsened × ×: Itching worsened Evaluation criteria for the degree of continuation of itch improvement ◎: 120 minutes or more ○: 60 minutes or more and less than 120 minutes △: 20 minutes or more and less than 60 minutes ×: Duration of less than 20 minutes −: No improvement in itch, Or worse

[0051]

[Table 6]

[0052]

[Table 7]

Further, the following commercial products were used in place of hydroxypropylmethyl cellulose, and as a result, good evaluation results (antiseptic properties, hypoallergenicity, improvement of itch / congestion, and persistence) were obtained. Further, the eye drops of Table 9 also showed good evaluation results. Hydroxypropyl methylcellulose (“Metroses 60
SH-50 "Metroses 65SH-50""Metroses65SH-40"
0 "," Metroses 65SH-1500 "" Metroses 65SH-400 "
0 ", all manufactured by Shin-Etsu Chemical Co., Ltd. Methyl cellulose (" Metroses SM-100 "" Metroses "
"SM-400""MetrosesSM-1500""MetrosesSM-400"
0 ", all manufactured by Shin-Etsu Chemical Co., Ltd.

[0054]

[Table 8]

[0055]

[Table 9]

All of the nasal drops in Table 9 were excellent in antiseptic properties, hypoallergenicity, improvement of runny nose / clogging, and durability.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61P 27/14 A61P 27/14 27/16 27/16 29/00 29/00 37/08 37/08 F Term (reference) 4C076 AA12 BB24 BB25 CC04 DD37 DD38 DD50R DD60 DD67 EE09 EE16 EE23 EE32 EE53

Claims (8)

[Claims] 1. A composition for external mucosa containing trometamol and terpenoids. 2. At least one selected from the group consisting of polyhydric alcohols, glycyrrhizic acids, and berberines.
A compound containing one or more compounds, characterized in that
The composition for external mucosa according to. 3. The composition for external mucosa according to claim 1, further comprising a water-soluble polymer compound. 4. The composition for external mucosa according to claim 1, which does not contain a preservative. 5. The composition for external preparation for mucosa according to claim 1, which is a pharmaceutical composition for anti-inflammatory and / or anti-allergy. 6. The composition for external mucosa according to claim 1, which is an ophthalmic or otolaryngological composition. 7. An antiseptic composition for an external preparation for mucosa, which contains trometamol and terpenoids. 8. A method for improving the antiseptic effect of trometamol, which comprises blending terpenoids.