JP5959271B2 - Mucosal composition - Google Patents

Description

  The present invention relates to a composition for applying to mucosa, which has an excellent cleaning effect and suppresses irritation to mucous membranes.

  It is known that in the mucous membranes such as the pharynx, nasal cavity, and vagina, discomfort and inflammation are caused by the adhesion of foreign substances. In order to prevent and ameliorate such symptoms in the mucous membrane, it is considered effective to remove the mucosal foreign matter with a mucous membrane washing solution or the like. By using a cleaning agent such as a surfactant at the time of cleaning, an excellent cleaning effect can be exhibited. As the surfactant, an anionic surfactant is generally used. Among these, alkyl sulfate type surfactants represented by lauryl sulfate and the like are known to have an excellent cleaning action. However, alkyl sulfate type surfactants are usually applied to the skin and hair, and have strong irritation to mucous membranes such as the pharynx, nasal cavity, vagina and oral cavity. When applied to the skin, it may swell red (erythema) or the mucous membrane may peel off. Therefore, the alkyl sulfate ester type surfactant is not used for mucous membranes despite its excellent cleaning effect.

  In addition, with regard to oral mucosa, in recent years, there has been an increase in the number of people who have dry mouth, especially oral mucosa, due to the decrease in saliva secretion due to increased mouth breathing, aging, stress, drug side effects, etc. Yes. When the oral mucosa is dried, the irritation sensitivity of the oral mucosa is increased. Therefore, when an oral detergent containing an alkyl sulfate ester type surfactant is used, a strong irritation is felt and discomfort is generated. For this reason, there is a restriction on the amount of the alkyl sulfate type surfactant contained in the oral cleaning agent.

  Against this background, a method for reducing irritation caused by lauryl sulfate, which is an alkyl sulfate ester type surfactant, has been studied, and contains a predetermined amount of lauryl sulfate and fatty acid amidopropyl betaine. A dentifrice composition (see, for example, Patent Document 1) has been proposed. However, although the composition described in Patent Document 1 contains lauryl sulfate, its content is as small as 0.2 to 0.7% by weight, and the cleaning effect by lauryl sulfate is not so much. In the first place, it is considered that the irritation is reduced because the content of lauryl sulfate is small. That is, by containing lauryl sulfate at a high concentration, a composition in which irritation to the mucous membrane was reduced while exhibiting an excellent cleaning effect has not yet been obtained.

JP 2009-084277 A

  The main object of the present invention is to provide a composition for applying to mucosa which has an excellent cleaning effect and suppresses irritation to mucous membranes.

As a result of intensive studies to solve the above problems, the inventors of the present invention specified an alkyl sulfate ester type surfactant, an imidazolinium betaine type amphoteric surfactant and / or a fatty acid amidopropyl betaine type amphoteric surfactant. The composition contained in the above-mentioned content ratio has an excellent usability because it suppresses the irritation caused by the alkylsulfuric acid ester type surfactant while having a sufficient cleaning effect when applied to the mucous membrane. I found it. The present invention has been completed as a result of further research based on such knowledge. That is, this invention provides the composition for mucosa of the following aspect.
Item 1. (A) an alkyl sulfate ester type surfactant, and (B) at least one surfactant selected from the group consisting of an imidazolinium betaine type amphoteric surfactant and a fatty acid amidopropyl betaine type amphoteric surfactant. Including
The content of the component (A) at the time of use is 3% by weight or more,
(B) Mucosal application composition whose content of a component is 0.45-3.5 weight part with respect to 1 weight part of (A) component.
Item 2. The composition for applying to mucosa according to Item 1, wherein the content of the component (A) at the time of use is 3 to 5% by weight.
Item 3. Item 3. The mucosa-applied composition according to Item 1 or 2, wherein the component (A) is selected from the group consisting of sodium octyl sulfate, sodium decyl sulfate, sodium lauryl sulfate, sodium myristyl sulfate, sodium palmityl sulfate, and sodium stearyl sulfate.
Item 4. Item 4. The composition for applying to mucosa according to any one of Items 1 to 3, wherein the component (B) is an imidazolinium betaine type amphoteric surfactant.
Item 5. Item 5. The composition for applying to mucosa according to Item 4, wherein the content of the component (B) is 0.7 to 3 parts by weight relative to 1 part by weight of the component (A).
Item 6. Item 4. The composition for applying to mucosa according to any one of Items 1 to 3, wherein the component (B) is a fatty acid amidopropyl betaine type amphoteric surfactant.
Item 7. Item 7. The composition for applying to mucosa according to Item 6, wherein the content of the component (B) is 0.5 to 3 parts by weight with respect to 1 part by weight of the component (A).
Item 8. Item 8. The composition for applying to mucosa according to any one of Items 1 to 7, wherein the mucous membrane is at least one mucosa selected from the group consisting of nasal cavity, pharynx, oral cavity, ear, vagina, bladder and rectum.

  According to the present invention, an excellent cleaning effect can be achieved by containing an alkyl sulfate ester type surfactant at a high concentration. In addition, since a high concentration of alkyl sulfate type surfactant has strong irritation to mucous membranes, it has been difficult to apply to mucous membranes conventionally. However, the composition applied to mucosa of the present invention reduces such irritation to mucous membranes. It has been done. Therefore, according to the composition for applying to mucosa of the present invention, it is possible to simultaneously realize a high cleaning effect and an excellent usability.

  The composition applied to mucosa of the present invention is selected from the group consisting of (A) an alkyl sulfate type surfactant, (B) an imidazolinium betaine type amphoteric surfactant, and a fatty acid amidopropyl betaine type amphoteric surfactant. And at least one surfactant, the content of the component (A) in use is 3% by weight or more, and the content of the component (B) is 0.45 to 3 parts by weight with respect to 1 part by weight of the component (A). .5 parts by weight. Hereinafter, the composition applied to mucosa of the present invention may be abbreviated as “the composition of the present invention”.

(A) Component The alkyl sulfate ester type surfactant used as the component (A) (hereinafter sometimes abbreviated as “(A) component”) is not particularly limited, and is generally used as an anionic surfactant. Widely used ones can be used.

  Although it does not restrict | limit especially about carbon number of the alkyl group which comprises an alkyl sulfate ester type surfactant, For example, 8-20, Preferably it is 10-18, More preferably, 10-16 is mentioned. Moreover, the alkyl group constituting the alkyl sulfate ester type surfactant may be either linear or branched, but preferably is linear. In addition, as the alkyl sulfate ester type surfactant, either a free form or a salt form may be used. Examples of the salt of the alkyl sulfate ester type surfactant include alkali metal salts such as sodium, potassium and magnesium, alkaline earth metal salts, and ammonium salts.

  Specific examples of the alkyl sulfate type surfactant include sodium octyl sulfate, sodium decyl sulfate, sodium lauryl sulfate, sodium myristyl sulfate, sodium palmityl sulfate, and sodium stearyl sulfate. In the composition of the present invention, the alkyl sulfate ester type surfactant may be used alone or in combination of two or more. Among these alkyl sulfate ester type surfactants, lauryl sulfate and myristyl sulfate are preferred because of their high cleaning effect, preferably lauryl sulfate, more preferably alkali metal lauryl sulfate, and more preferably lauryl sulfate. Sodium is mentioned. Sodium lauryl sulfate is commercially available from, for example, Daiichi Kogyo Seiyaku Co., Ltd. and Kao Corporation.

  In the composition of the present invention, the content of the component (A) at the time of use is usually 3% by weight or more, preferably 3 to 5% by weight, and more preferably 3 to 4% by weight. By containing the component (A) in such a range, an excellent cleaning effect by the alkyl sulfate ester type surfactant is obtained, and further, an imidazolinium betaine type amphoteric surfactant or a fatty acid amidopropyl betaine type described later is used. It is preferable because the effect of reducing irritation by containing an amphoteric surfactant is high. As described above, the composition of the present invention has excellent usability because the irritation to the mucous membrane is suppressed while containing the component (A) at a high concentration. In the present specification, the “content at the time of use” refers to the content of each component included when the composition of the present invention is applied to the mucous membrane.

(B) Component In the present invention, as the amphoteric surfactant, an imidazolinium betaine type amphoteric surfactant and / or a fatty acid amidopropyl betaine type amphoteric surfactant represented by the following general formula is used. Hereinafter, these surfactants may be abbreviated as “component (B)”.

The imidazolinium betaine type amphoteric surfactant used as the component (B) in the present invention is represented by the following general formula (1) or the following general formula (2).

In the formula (1), R ¹ represents a linear or branched alkyl group having 8 to 22 carbon atoms, preferably 10 to 18 carbon atoms. For example, decyl group, lauryl group, myristyl group, palmityl group, stearyl Group, oleyl group and the like, preferably lauryl group, palmityl group, stearyl group and the like.

Further, in formula (1), R ² and R ³ are the same or different, represent a linear or branched alkylene group having 1 to 3 carbon atoms, e.g., methylene, ethylene, n- propylene Group, i-propylene group and the like, preferably methylene group and ethylene group.

In formula (1), Q ¹ represents —COO 2 ^— or COOM ¹ (M ¹ represents a hydrogen atom or an alkali metal atom. Examples of the alkali metal atom include sodium, potassium, magnesium, etc., preferably sodium. Can be mentioned.

In the formula (2), R ⁴ represents a linear or branched alkyl group having 8 to 22 carbon atoms, preferably 10 to 18 carbon atoms, such as a decyl group, a lauryl group, a myristyl group, a palmityl group, A stearyl group, an oleyl group, etc. are mentioned, Preferably a lauryl group, a palmityl group, and a stearyl group are mentioned.

R ⁵ and R ⁶ are the same or different and represent a linear or branched alkylene group having 1 to 3 carbon atoms, such as methylene group, ethylene group, n-propylene group, i-propylene group, etc. Preferably, a methylene group and an ethylene group are mentioned.

In formula (2), Q ² is represented by —COO ^{2 —} or COOM ² . Here, M ² represents a hydrogen atom or an alkali metal atom. Examples of the alkali metal atom include sodium, potassium, magnesium and the like, preferably sodium.

In formula (2), R ⁷ represents a hydroxyl group or a carboxyalkoxy group represented by —O—R ^7a —COOM ³ , and R ^7a is a linear or branched chain having 1 to 3 carbon atoms. An alkylene group is represented by, for example, a methylene group, an ethylene group, an n-propylene group, an i-propylene group and the like, preferably a methylene group and an ethylene group. M ³ represents a hydrogen atom or an alkali metal atom. Examples of the alkali metal atom include sodium, potassium, magnesium and the like, preferably sodium.

  Specific examples of imidazolinium betaine-type amphoteric surfactants include N-cocoyl-N′-carboxymethyl-N′-hydroxyethylethylenediamine sodium, N-cocoyl-N′-carboxymethoxyethyl-N′-carboxymethylethylenediamine. Disodium, sodium undecylhydroxyethylimidazolinium betaine, 2-undecyl-N, N, N- [hydroxyethylcarboxymethyl] -2-imidazoline sodium, N-lauroyl-N-carboxymethyl-N-hydroxyethylethylenediamine sodium , 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine and the like. In the present invention, imidazolinium betaine-type amphoteric surfactants may be used singly or in combination of two or more. Among these imidazolinium betaine-type amphoteric surfactants, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine is preferably used from the viewpoint of exhibiting an excellent stimulus-reducing effect. 2-Alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine is commercially available from Lion Corporation, Kao Corporation, and the like.

Moreover, the fatty acid amide propyl betaine type | mold amphoteric surfactant used as (B) component in this invention is shown by following General formula (3).

In the formula (3), R ⁸ represents a linear or branched alkyl group having ⁸ to 20 carbon atoms, preferably 10 to 16 carbon atoms, more preferably 12 to 14 carbon atoms, such as a decyl group. Lauryl group, myristyl group, palmityl group, stearyl group, oleyl group and the like, preferably lauryl group, myristyl group and the like.

  Specific examples of fatty acid amidopropyl betaine-type amphoteric surfactants include lauric acid amidopropyl betaine, palm oil fatty acid amidopropyl betaine, isostearic acid amidopropyl betaine, linolenic acid amidopropyl betaine, palm oil fatty acid amidopropyl betaine, myristic acid amide And propylbetaine. In the present invention, the fatty acid amidopropyl betaine type amphoteric surfactant may be used alone or in combination of two or more. Among these fatty acid amidopropyl betaine type amphoteric surfactants, lauric acid amidopropyl betaine and coconut oil fatty acid amidopropyl betaine are preferable from the viewpoint of exhibiting an excellent stimulus-reducing effect. Lauric acid amidopropyl betaine and coconut oil fatty acid amidopropyl betaine are commercially available from Kao Corporation, Sanyo Kasei Kogyo Co., Ltd., Shin Nippon Chemical Co., Ltd., and the like.

  In the composition of the present invention, the component (B) is preferably 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauric acid, from the viewpoint that irritation to the mucous membrane is further significantly reduced. Examples thereof include at least one selected from the group consisting of amidopropyl betaine and coconut oil fatty acid amidopropyl betaine.

  The content of the component (B) at the time of use in the composition of the present invention is set to 0.45 to 3.5 parts by weight with respect to 1 part by weight of the component (A). By containing the component B), it is possible to reduce irritation to the mucous membrane while exhibiting the excellent cleaning effect of the component (A). From the viewpoint of further reducing irritation to the mucous membrane, the content of the component (B) at the time of use is preferably 0.5 to 3 parts by weight, more preferably 0 with respect to 1 part by weight of the component (A). 0.7 to 2.5 parts by weight, more preferably 0.8 to 2.5 parts by weight. Here, the content of the component (B) is the total amount when two or more compounds are used as the component (B).

  In particular, when the component (B) is an imidazolinium betaine type amphoteric surfactant, the content of the component (B) is 0.45 to 3.5 parts by weight, preferably 1 part by weight of the component (A). Is 0.7 to 3 parts by weight, more preferably 0.8 to 2.5 parts by weight.

  In particular, when the component (B) is a fatty acid amidopropyl betaine type amphoteric surfactant, the content of the component (B) is 0.45 to 3.5 parts by weight, preferably 1 part by weight of the component (A). Is 0.5 to 3 parts by weight, more preferably 0.7 to 3 parts by weight, and particularly preferably 0.8 to 2.5 parts by weight.

  The solvent used in the composition of the present invention is not particularly limited as long as it is pharmaceutically acceptable and can dissolve each of the above components. For example, distilled water, ion-exchanged water, physiological saline, phosphoric acid Examples include buffered saline and polyhydric alcohol.

  Moreover, the composition of this invention may contain the conventionally well-known additive pharmaceutically acceptable in the range which does not impair the effect of this invention in addition to the said component. Examples of additives include preservatives, sweeteners, fragrances, colorants, wetting agents, emulsifiers, solubilizers, thickeners, thickeners, foaming agents, enzymes, pigments, plant extracts, excipients, Examples include, but are not limited to, pH adjusters, tonicity agents, cooling agents, chelating agents, and the like. Moreover, you may contain pharmacologically active components, such as an antibacterial agent, an anti-inflammatory agent, an anesthetic, an analgesic, a deodorant, an antifungal agent, and an antiviral agent.

  The pH of the composition of the present invention is not particularly limited as long as it does not damage the mucosa when applied to the mucosa, and examples thereof include 4 to 8, preferably 4 to 6. When adjusting the composition of the present invention to such a pH, it can be performed according to a conventionally known method, for example, hydrochloric acid, citric acid, gluconic acid, succinic acid, acetic acid, tartaric acid, sorbic acid, lactic acid, maleic acid. , Sulfuric acid, phosphoric acid, malic acid, arginine, aqueous ammonia, diisopropanolamine, diethanolamine, triisopropanolamine, triethanolamine, monoethanolamine, potassium hydroxide, calcium hydroxide, sodium hydroxide, and salts thereof Buffering agents can be added as appropriate.

  Moreover, it is desirable that the osmotic pressure of the composition of the present invention is adjusted to an osmotic pressure within a physiologically acceptable range. Such osmotic pressure is 150 to 400 mOsm, preferably 200 to 400 mOsm, and more preferably 200 to 290 mOsm. By adjusting the osmotic pressure to such a range, the irritation to the mucous membrane can be further reduced.

  The composition of the present invention can be obtained by mixing the above components according to a method usually employed in the art. Although the dosage form of the composition of this invention is not specifically limited, For example, forms, such as a liquid agent, a paste agent, an ointment, a powder agent, a granule, a tablet, a cream agent, are mentioned. Examples of the use of the composition of the present invention include intestinal cleanser, rectal cleanser, bladder cleanser, vaginal cleanser, ear cleanser, mouth rinse, oral cleanser, nasal cleanser, etc. Preferable examples include vaginal cleanser, ear cleanser, gargle, oral cleanser, nasal cleanser and the like. In addition, the composition of the present invention may be provided as a product containing the components (A) and (B) at the above concentrations, and is appropriately diluted with water or the like at the time of use, and the components (A) and (B) are contained in the above concentrations. It may be provided as a concentrate prepared to be in range.

  The mucous membrane to which the composition of the present invention is applied is not particularly limited, but can be applied to mucous membranes such as nasal cavity, pharynx, oral cavity, ear, vagina, bladder, rectum, and preferably nasal cavity, pharynx , Oral, ear and vaginal mucosa.

  The composition of the present invention is suitably used for washing mucous membranes because of its high washing effect and reduced irritation to mucous membranes. The method of using the composition of the present invention for the purpose of washing the mucous membrane is not particularly limited as long as the cleaning effect is exerted. For example, a method of dripping onto the mucosa, a method of spraying on the mucosa by spraying, a catheter For example, there are a method of injecting by a nasal cavity, a method of pouring a cleaning solution into the nasal cavity and spitting it out of the mouth, a method of rinsing by mouth in the mouth and a method of brushing with a brush. In addition, the amount of the composition of the present invention applied at that time is not particularly limited and may be appropriately set in consideration of the size of the application site, the degree of foreign matter adhering to the mucous membrane, etc. 10 to 30 mL, preferably 15 to 25 mL, and 0.2 to 1 mL, preferably 0.2 to 0.7 mL, oral mucosa 5 to 30 mL, preferably 10 to 20 mL is exemplified for the purpose of cleaning.

  Hereinafter, the present invention will be described in more detail, but the present invention is not limited thereto.

[Reference Test Example 1]
Evaluation of the compositions of Examples and Comparative Examples described later on the mucosa was performed using human three-dimensional cultured skin instead of human mucosa or animal mucosa. Therefore, the following preliminary test was conducted in order to confirm that the stimulation to the guinea pig mucosa and the confirmation method using human three-dimensional cultured skin were correlated in advance.

  Guinea pigs (female, 6 weeks old, 30 animals) were obtained from Shanghai Ginger Experimental Animal Farming Co., Ltd. The skin just below the lower lip of the guinea pig is pulled down to expose the anterior tooth gingiva and the lower lip mucosa, and 100 μL of the composition described in Table 1 below is administered dropwise to the exposed oral mucosa, and the composition is applied for 30 seconds. Painted with a paint brush. The administration was performed 4 times a day for 4 days every 2 hours. On the 1st and 3rd day after the end of administration, changes in the anterior gingival and lower lip mucosa were detected by the CTFA Guidelines (Hynes, CR, and Estrin, NF, CTFA Safety Testing Guidelines: CTFA Technical Guidelines, Cosmetic, Toiletry and Fragarance Association). , Inc., Washington, 11-13 (1981)).

(Evaluation method of cell viability)
MTT (3- [4,5-dimethylthiazol-2-yl] -2,5- is used to measure the number of viable cells after adding the compositions of Reference Formulas 1 to 4 shown in Table 1 below to the medium. diphenyltetrazole bromide) assay was performed. The evaluation procedure is as follows.

Obtain a human three-dimensional culture epidermis (LabCyte EPI-MODEL24) manufactured by Japan Tissue Engineering Co., Ltd. (hereinafter J-TEC), and place it in a 24-well assay plate containing the attached assay medium (0.5 mL). The human three-dimensional culture epidermis was previously adhered to the bottom of the cup) and cultured for 2 hours in an incubator set at 37 ° C. and 5% CO ₂ . 25 μL each of the compositions of Reference Formulas 1 to 4 shown in Table 1 below was dropped on the human three-dimensional culture epidermis and further cultured for 2 hours. After culturing, the surface of the human three-dimensional cultured epidermis was washed with PBS (−) 10 times or more, and then 0.5 mg / mL MTT test solution (3- (4,5-dimethyl-2-thiazolyl bromide-2, Using 5-diphenyl-2H-tetrazolium (manufactured by Dojindo Laboratories Co., Ltd.), MTT staining of living cells was performed by incubating at 37 ° C. under 5% CO ₂ for 3 hours. After completion of MTT staining, the human three-dimensional cultured epidermis was immersed in 300 μL of isopropanol in the dark at 20 to 25 ° C. for 16 hours to obtain a cell extract. The absorbance of this cell extract at 570 nm was measured. The cell viability was calculated according to the following formula (1). The absorbance of the blank is a value measured using isopropanol.

Cell viability (%) = (absorbance of cell extract−absorbance of blank) /
(Absorbance of PBS (−) − absorbance of blank) × 100 (1)

The results are shown in Table 1 below.

  From the results shown in Table 1, it was shown that the lower the animal score (ie, the less stimulation), the higher the cell survival rate, and the correlation between the two. These results were also shown to correlate with irritation in humans. Furthermore, it was shown that the composition containing 3% by weight or more of the component (A) sodium lauryl sulfate and not containing the component (B) has strong irritation to the mucous membrane. In addition, the composition for oral cavity whose animal score is 0-2 is accept | permitted on the market.

[Reference Test Example 2]
The cell viability was evaluated when the content of sodium lauryl sulfate was less than 3% by weight. Evaluation is the same as that in Reference Test Example 1 (Method for evaluating cell viability) except that 25 μL of an aqueous solution containing 1.5% by weight or 2% by weight of sodium lauryl sulfate is dropped on the human three-dimensional cultured epidermis. went.

  As a result, the cell viability when the content of sodium lauryl sulfate is 1.5% by weight is 46.5%, and the cell viability when the content of sodium lauryl sulfate is 2% by weight is 36.5%. Met. That is, when a composition containing less than 3% by weight of component (A) was applied to the mucous membrane, it was shown that it was a weak irritation although there was mucosal irritation. On the other hand, when the content of component (A) was 3% by weight or more, the cell viability was 0%, indicating that mucosal irritation was particularly strong (see Table 2 below).

[Test example]
Cell viability was evaluated according to the same method as in Reference Test Example 2 except that the compositions shown in Tables 2 to 10 below were dropped onto the human three-dimensional cultured epidermis. The compositions shown in Tables 2 to 10 below were prepared by dissolving the components (A) and (B) in water.

The raw materials used in this test are as follows.
Sodium lauryl sulfate (Monogen Y-100): Daiichi Kogyo Seiyaku Co., Ltd. 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine (Enadicol C40H): Lion Corporation Lauramide amidopropyl betaine (Ricavion B-) 300): Nippon Oil Chemical Co., Ltd. Coconut oil fatty acid amidopropyl betaine (Levon 2000): Sanyo Chemical Industries, Ltd.

  The cell viability when 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine is used as the component (B) is shown in Tables 2 to 5 below.

  As can be seen from Reference Examples 2 to 4 in Table 2, when the content of sodium lauryl sulfate is less than 3% by weight, the cell survival rate is 29% or more and there is mucosal irritation, but it may be weak irritation. Indicated. On the other hand, as can be seen from Comparative Examples 1, 5, and 7, when the content of sodium lauryl sulfate was 3% by weight or more, the cell viability was 0%, indicating that mucosal irritation was particularly strong. Here, as can be seen from a comparison between Examples 1 to 8 and Comparative Examples 1 to 4 in Table 3, even when 3% by weight of sodium lauryl sulfate is contained, 2-alkyl-N-carboxymethyl-N -It was shown that by containing hydroxyethylimidazolinium betaine at a predetermined content ratio, cell viability was significantly increased and mucosal irritation was reduced. Further, as can be seen from Tables 4 and 5, the irritation reduction effect is obtained when sodium lauryl sulfate is contained in an amount of more than 3% by weight (for example, when the content of sodium lauryl sulfate is 4% by weight and 5% by weight). ) Showed a similar tendency.

The cell viability when lauric acid amidopropyl betaine is used as the component (B) is shown in Tables 6 to 8 below.

The cell viability when coconut oil fatty acid amidopropyl betaine is used as the component (B) is shown in Tables 9 and 10 below.

  As can be seen by comparing Examples 18 to 24 in Table 6 with Comparative Examples 1, 11 and 12, even when containing 3% by weight of sodium lauryl sulfate, amidopropyl betaine laurate at a predetermined content ratio. It was shown that the cell viability was remarkably increased and the mucosal irritation was reduced by the inclusion. Further, as can be seen from Tables 7 and 8, the irritation reduction effect is obtained when sodium lauryl sulfate is contained in an amount of more than 3% by weight (for example, when the content of sodium lauryl sulfate is 4% by weight and 5% by weight). ) Showed a similar tendency. In addition, as can be seen from Tables 9 and 10, when the coconut oil fatty acid amidopropyl betaine is contained at a predetermined content ratio with respect to sodium lauryl sulfate, the irritation reducing effect includes lauric acid amidopropyl betaine. It was shown that the same tendency as in the case of

  From the above results, it was shown that when the content of the alkyl sulfate type surfactant in the composition is 3% by weight or more, strong irritation occurs in the mucous membrane. Irritation to the mucous membrane caused by containing a large amount of imidazolinium betaine-type amphoteric surfactant or fatty acid amidopropyl betaine-type amphoteric surfactant in a predetermined content ratio is significantly reduced. Was shown to be.

  In particular, when the alkyl sulfate type surfactant is contained in an amount of 3% by weight or more and the imidazolinium betaine type amphoteric surfactant or the fatty acid amidopropyl betaine type amphoteric surfactant is not contained, the cell viability becomes 0%. It was shown that strong irritation was generated in the mucous membrane, but it was shown that the irritation was reduced by containing an imidazolinium betaine-type amphoteric surfactant or a fatty acid amidopropyl betaine-type amphoteric surfactant. .

  In addition, if the content of the alkyl sulfate type surfactant is 3% by weight or more, the imidazolinium betaine type amphoteric interface can be used regardless of the concentration of the alkyl sulfate type surfactant. It was shown that the stimulus-reducing effect by containing an activator or a fatty acid amidopropyl betaine type amphoteric surfactant so as to have a predetermined content ratio has the same tendency.

[Prescription example]
The composition described in the following formulation examples was prepared by mixing raw materials by a conventionally known method. In any case, the composition applied to mucosa was excellent in cell viability and low in irritation as in the Examples.

Claims (7)

(A) an alkyl sulfate ester type surfactant, and (B) at least one surfactant selected from the group consisting of an imidazolinium betaine type amphoteric surfactant and a fatty acid amidopropyl betaine type amphoteric surfactant. Including
The content of the component (A) at the time of use is 3% by weight or more ,
When the component (B) is an imidazolinium betaine type amphoteric surfactant, the content of the component (B) is 0.7 to 3 parts by weight with respect to 1 part by weight of the component (A).
When the component (B) is a fatty acid amidopropyl betaine type amphoteric surfactant, the content of the component (B) is 0.46 to 3.5 parts by weight with respect to 1 part by weight of the component (A),
A mucosa-applied composition applied to at least one mucosa selected from the group consisting of nasal cavity, pharynx, oral cavity, ear, vagina, bladder and rectum .   The composition for applying to mucosa according to claim 1, wherein the content of the component (A) at the time of use is 3 to 5% by weight.   The composition for mucosa according to claim 1 or 2, wherein the component (A) is selected from the group consisting of sodium octyl sulfate, sodium decyl sulfate, sodium lauryl sulfate, sodium myristyl sulfate, sodium palmityl sulfate and sodium stearyl sulfate.   The composition for mucosa according to any one of claims 1 to 3, wherein the component (B) is an imidazolinium betaine type amphoteric surfactant. The composition for mucosa according to claim 4, wherein the content of the component (B) is 0.8 to 2.5 parts by weight with respect to 1 part by weight of the component (A).   The composition for mucosa according to any one of claims 1 to 3, wherein the component (B) is a fatty acid amidopropyl betaine type amphoteric surfactant.   The composition for mucosa according to claim 6, wherein the content of the component (B) is 0.5 to 3 parts by weight per 1 part by weight of the component (A).