JP2005139074A - Inhibitor of production of enterotoxin by staphylococcus aureus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an inhibitor of the production of enterotoxins by Staphylococcus aureus which effectively inhibits the production of enterotoxins by Staphylococcus aureus without affecting the normal bacterial flora in the skin and the intestine, is useful for the prevention of the exacerbation of allergic diseases involved with a superantigen, such as atopic dermatitis, or the mitigation of the condition of the diseases and the prevention of food poisoning, and excels in stability and safety. <P>SOLUTION: The inhibitor of the production of enterotoxins by Staphylococcus aureus comprises an extract of Caulerpa lentillifera. The inhibitor is obtained by incorporating an extract of one or more plants selected from Humulus lupulus L., Forsythia suspensa Vahl, Forsytha viridissima Lindl., Forsythia koreana Nakai, Calendula officinalis L., Calendula arvensis L., Lonicera japonica Thunb., Lonicera gracilipes Miq. var. glabra Miq., Salvia officinalis L. and its variety, Gardenia jasminoides Ellis and its same genus plants, Sasa veitchii Rehd., Urtica thunbergiana Sieb. et Zucc., Laporteamacrostachya Ohwi, Isodon japonicus Hara, and Isodon trichocarpus Kudo in combination with the extract of Caulerpa lentillifera into a carrier or a base. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

The present invention can specifically inhibit enterotoxin production by Staphylococcus aureus without affecting the bacterial flora in the skin and intestines, and exacerbation of allergic diseases involving these as superantigens. S. aureus enterotoxin production inhibitor useful for prevention or alleviation and prevention of food poisoning caused by Staphylococcus aureus, and atopic dermatitis exacerbation or alleviation agent, food poisoning prevention agent, and food containing the same Regarding additives.

Staphylococcus aureus is a Gram-positive bacterium that causes vomiting-related food poisoning and various abscesses. The enterotoxin produced by this method causes food poisoning, and as a superantigen like enterotoxin B and toxic shock syndrome toxin-1 (TSST-1), exacerbation of atopic dermatitis Those related to allergic diseases are known. Enterotoxin B has a property of directly binding to a class II molecule of a major histocompatibility complex on an antigen presenting cell and a Vβ region of a T cell receptor as a superantigen without being processed by the antigen presenting cell. It is believed that the T cell group expressing a specific Vβ that binds to the superantigen is activated at once to promote the production of a large amount of cytokines and to have a significant effect on the immune response of the living body. Enterotoxin B and TSST-1, which are superantigens of S. aureus, stimulate skin Langerhans cells and macrophages to produce interleukin-1, tumor necrosis factor, and interleukin-12. Induces the expression of skin lymphocyte-binding antigen (CLA), a skin homing receptor, in activated T cells.

  As mentioned above, as enterotoxin produced by Staphylococcus aureus is found to be involved in allergic diseases in addition to food poisoning, active screening of drugs with antibacterial or bactericidal activity against Staphylococcus aureus has been actively conducted. I have been. As such drugs, recently, Mannentake fruit body umbrella extract (see Patent Document 1), antibacterial spices such as clove, allspice, oregano (see Patent Document 2), Kudin extract (see Patent Document 3), Jackfruit Extract (see Patent Literature 4), altocarpine and sophoraflavanone G (see Patent Literature 5), xanthone derivative (see Patent Literature 6), birch extract (see Patent Literature 7), chitosan derivative (see Patent Literature 8), Fine particle titanium oxide having photocatalytic activity (see Patent Document 9), stevia extract (see Patent Document 10), alkenyl isothiocyanate compound (see Patent Document 11), hop, forsythia, syringen, chrysanthemum, tokinsenka, calendula , Honeysuckle, Warbler, Salvia and its variants None and genus plant, striped bamboo, nettle, Miyama Nettle causes, such as one or more plant extracts selected from Kurobanahikiokoshi (see Patent Document 12) are disclosed.

  Also known are detergents containing N-acylglutamate for the removal of Staphylococcus aureus (see Patent Document 13) and bacterial enterotoxin neutralizers containing iron-bound lactoferrin (see Patent Document 14). It has been.

However, most of the techniques described above are intended to bacteriostatically or kill or eliminate Staphylococcus aureus. Staphylococcus epidermidis , Bacteroides , Eubacterium , Streptococcus ( Steptococcus ), bifidobacteria ( Bifidobacterium genus) skin and intestinal bacteria are also bacteriostatic and bactericidal, or they are removed, resulting in changes in the resident flora. May affect the homeostasis of the gut and intestines, resulting in the risk of opportunistic infections. Moreover, since the enterotoxin neutralizer which has a lactoferrin as a main component is a protein formulation, there are many restrictions in obtaining a stable formulation, and expression of sensitization is also feared.

Sea vines are seaweeds belonging to the Chlorophyceae Caurelpacae genus Caulerpa , and are widely distributed in the southern Pacific Ocean of the main island, Kyushu, the Nansei Islands, the Pacific Ocean, and the Indian Ocean. Sometimes called green caviar. It is also cultivated in Okinawa, and is used for edible vinegar. Various studies have been conducted on the effectiveness of sea urchin grape extract, and hyaluronidase inhibitors (see Patent Document 15), slimming agents (see Patent Document 16), A hair restorer (see Patent Document 17) has been disclosed so far. Moreover, hyaluronic acid production effect (refer patent document 18) etc. are known as effectiveness of sea urchin grapes.

JP-A-6-116162 JP-A-7-267873 JP-A-8-73364 JP-A-8-73368 JP-A-8-73372 Japanese Patent Laid-Open No. 9-110688 JP-A-10-120589 JP 10-158305 A Japanese Patent Laid-Open No. 11-5729 Japanese Patent Laid-Open No. 11-43443 Japanese Patent Laid-Open No. 11-137949 JP 2001-226280 A Japanese Patent Laid-Open No. 11-80781 Japanese Patent Laid-Open No. 11-279076 JP 09-67266 A JP 2000-72642 A JP 2001-55314 A JP 2003-128573 A

  Therefore, in the present invention, the production of enterotoxins by Staphylococcus aureus is effectively suppressed without affecting the resident flora in the skin and intestines, and allergenicity involving superantigens, such as exacerbation of atopic dermatitis. The purpose of the present invention is to obtain a Staphylococcus aureus enterotoxin production inhibitor that is useful in preventing disease exacerbation or alleviating symptoms and preventing food poisoning and is excellent in stability and safety.

  As a result of various studies to solve the above-mentioned problems, we found an enterotoxin production-inhibiting action of Staphylococcus aureus specific in the sea urchin grape extract, and further, the action is stably maintained in various preparation systems, and at an effective concentration, After confirming that no oral toxicity, skin irritation, sensitization, teratogenicity, etc. were exhibited, the present invention was completed.

Furthermore, Umibudou extract and hops (Humulus lupulus L.), Forsythia (Forsythia suspensa Vahl), Sina Forsythia (Forsythia viridissima Lindl.), Korean Forsythia (Forsythia koreana Nakai), tow calendula (Calendula officinalis L.), marigold ( Calendula arvensis L.), honeysuckle (Lonicera japonica Thunb.), warbler Kagura (Lonicera gracilipes Miq. var. glabra Miq.), salvia (Salvia officinalis L.) and its variants, gardenia (Gardenia jasminoides Ellis) and same genus plant, Kumazasa (Sasa veitchii Rehd.), nettle (Urtica thunbergiana Sieb. et Zucc. ), Miyama nettle (Laportea macrostachya Ohwi), cause (Isodon japonicus Hara), Kurobanahikiokoshi (Isodon trichocarpus Kudo) 1, two or more selected from By combining the plant extract in combination, a specific yellow bud It was found that staphylococcal enterotoxin production inhibitory action is synergistically improved.

  That is, in the present invention, the cedar grape extract alone or in combination with the above-described plant extract is contained in a carrier or base to form a Staphylococcus aureus enterotoxin production inhibitor, and the enterotoxin production inhibitor is used as a carrier or the like. To obtain an atopic dermatitis exacerbation or alleviation agent, food poisoning preventive agent and food additive for food poisoning prevention.

  As described in detail above, the present invention effectively suppresses enterotoxin production by Staphylococcus aureus without affecting the resident flora in the skin and intestines, and is excellent in stability and safety. An enterotoxin production inhibitor could be obtained. This S. aureus enterotoxin production inhibitor is useful for preventing exacerbation or alleviating symptoms of allergic diseases involving superantigens such as exacerbation of atopic dermatitis and preventing food poisoning.

  First, sea vines and plants used to obtain an extract in the present invention will be described.

The Umibudou in obtaining the Umibudou extract, can be used Umibudou (Caurelpa lentillifera), and Kaurerupa racemosa (Caulerpa racemosa) algae. The Kaurerupa racemosa (Caulerpa racemosa) algae, Kaurerupa racemosa (Caulerpa racemosa) it is known that a number of variants are present in addition, as a variant, Sen'naridzuta (Caurelpa racemosa var. Clavifera f. Macrophysa), Surikogidzuta (Caurelpa racemosa var. laete-virens), Hiraedzuta (Caurelpa racemosa var. lamourouxii), Etsukidzuta (Caurelpa racemosa var. occidentalis), Takatsukidzuta (Caurelpa racemosa var. peltata), Kohagidzuta (Caurelpa racemosa var. uvi fera), Kaurerupa racemosa Tsurubinata (Caulerpa racemosa var. turbinata) and the like are known. Umibudou, these, Umibudou (Caurelpa lentillifera), and Kaurerupa racemosa (Caulerpa racemosa) used as a generic term algae, can be used without particular distinction of the kind in the present invention. In addition, whole algae can be used for extraction. These may be subjected to an extraction operation as it is after being desalted, but in consideration of extraction efficiency, it is preferable to perform extraction after processing such as chopping, drying, and grinding.

Hop ( Humulus lupulus L.) is a plant of the herb “ Lupuli Strobilus ” and is a vine perennial belonging to the family Moraceae . Although various parts such as flowers, leaves, stems and fruits can be used, it is particularly preferable to use female flower spikes.

Forsythia suspensa Vahl, Forsythia viridissima Lindl. And Forsythia koreana Nakai are the basic plants of the herb " Forsythiae Fructus " and fallen in the Oleaceae family. is there. Each part such as a flower, a leaf, a branch, a trunk, and a fruit can be used, but it is particularly preferable to use a fruit.

The calendula ( Calendula officinalis L.) is an annual or biennial herb belonging to the Compositae family, and the calendula ( Calendula arvensis L.) is a related species. Although various parts such as flowers, leaves, and stems can be used, it is particularly preferable to use flowers.

Honeysuckle ( Lonicera japonica Thunb.) Is an evergreen vine that belongs to the Caprifoliaceae family and is also called Nindu. Warbler moth ( Lonicera gracilipes Miq. Var. Glabra Miq.) Is a related species. Although parts such as flowers, leaves, stems, branches and fruits can be used, it is particularly preferable to use leaves and stems.

Salvia (Salvia officinalis L.) is a perennial belonging to the Labiatae (Labiatae), as the variants include Salvia officinalis var. Tenuior. Flowers, leaves, stems and whole plants can be used.

Gardenia jasminoides Ellis and its related plants are evergreen shrubs belonging to the Rubiaceae family, and are the basic plants of the herbal medicine “ Gardeniae Fructus ”. The genus plant, Gardenia jasminoides var. Grandiflora Nakai) , include Kokuchinashi (Gardenia radicans Thunb.). Each part such as a flower, a leaf, a branch, a trunk, and a fruit can be used, but it is particularly preferable to use a fruit.

Kumazasa ( Sasa veitchii Rehd.) Is an evergreen monocotyledonous plant belonging to the Gramineae family, and can use parts of flowers, leaves, branches, buds, rhizomes, roots, etc., but leaves must be used. Is particularly preferred.

Nettle ( Urtica thunbergiana Sieb. Et Zucc.) And Laportea macrostachya Ohwi are perennials belonging to the family Urticaceae and can use parts of flowers, leaves, stems, etc. It is particularly preferred.

Cause (Isodon japonicus Hara) and Kurobanahikiokoshi (Isodon trichocarpus Kudo) is a perennial plant belonging to the Labiatae (Labiatae), a MotoHara plant of herbal "Enmeisou" (Isodonis Herba). Although parts such as flowers, leaves, stems, and roots can be used, it is particularly preferable to use the above-ground part.

  In the present invention, the above sea vines and the above plants may be subjected to extraction as they are, but considering the extraction efficiency, it is preferable to perform extraction after processing such as shredding, drying, and pulverization. Extraction is performed by immersing in an extraction solvent. In order to increase the extraction efficiency, stirring may be performed or homogenization may be performed in an extraction solvent. The extraction temperature is suitably about 5 ° C. to the boiling point of the extraction solvent. The extraction time varies depending on the type of extraction solvent and the extraction temperature, but is suitably about 4 hours to 14 days.

  Extraction solvents include water, lower alcohols such as methanol, ethanol, propanol, and isopropanol, polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, dipropylene glycol, and glycerin, and ethers such as ethyl ether and propyl ether. , Polar organic solvents such as esters such as ethyl acetate and butyl acetate, and ketones such as acetone and ethyl methyl ketone can be used, and one or more of these are selected and used. Further, physiological saline, phosphate buffer, phosphate buffered saline, or the like may be used.

  The above-described extract of sea vines and plants using the solvent can be used as it is as the S. aureus enterotoxin production inhibitor according to the present invention, but the concentrated and dried solids can be dissolved again in water or a polar solvent, or It may be used after performing purification treatment such as decolorization, deodorization, desalting, etc. within the range that does not impair the Staphylococcus aureus enterotoxin production inhibitory action, or after fractionation treatment by column chromatography. For storage, it can be freeze-dried after purification and dissolved in a solvent before use. In the present invention, extracts from the above-mentioned solvents of plants such as sea urchin and hops or the treated product as they are or in an aqueous carrier such as water, lower alcohol, emulsion, gel, cream, ointment or the like, Powdered or granulated to make S. aureus enterotoxin production inhibitor. It can also be encapsulated in vesicles such as liposomes or microcapsules.

  Therefore, the Staphylococcus aureus enterotoxin production inhibitor according to the present invention includes, as necessary, excipients such as starch, lactose, microcrystalline cellulose and magnesium aluminate metasilicate, lubricants such as magnesium stearate and talc, gelatin , Binders such as shellac, polyvinylpyrrolidone, methylcellulose, hydroxyethylcellulose, disintegrants such as carboxymethylcellulose calcium, humectants such as sorbitol, glycerin, antioxidants such as dibutylhydroxytoluene, butylhydroxyanisole, tocopherol, absorption promoters, With known methods such as surfactants and tonicity agents, soft capsules, hard capsules, tablets, pills, granules, powders, suspensions, liquids, syrups, emulsions, elixirs, etc. Oral, injection, suppository, pessary or It may be provided as a use agent.

  Since the S. aureus enterotoxin production inhibitor according to the present invention is hypoallergenic and does not exhibit toxicity or sensitization, it is particularly suitable for oral administration or topical application on the skin. It is useful as an oral preparation or food additive for the purpose of preventing exacerbation of allergic diseases involving superantigens such as exacerbation of atopic dermatitis, mitigating symptoms, and preventing food poisoning, and is also excellent in stability.

  Further, the features of the present invention will be described in detail with reference to examples.

[Extract 1]
Disperse 50 g of dried sea urchin grapes (from Palau) in 950 g of purified water. Allow to stand at 80 ° C. for 1 hour, filter the supernatant with gauze, and sterilize the filtrate using a 0.45 μm pore filter, then concentrate under reduced pressure to obtain the aqueous preparation according to Extract 1 100 g was obtained.

[Extract 2]
Disperse 10 g of dried crushed grapes (from Palau) in 990 g of purified water. The supernatant was filtered with gauze, and the filtrate was further sterilized using a 0.45 μm pore filter and concentrated under reduced pressure to obtain 100 g of an aqueous preparation according to Extract 2.

[Extract 3 to Extract 11]
250 g of each plant shown in Table 1 was dried, pulverized, immersed in 1.0 liter of a 50% by volume ethanol aqueous solution, and allowed to stand at 25 ° C. for 7 days for extraction. The extract was filtered to collect the filtrate and sterilized with a Millipore filter to obtain Extract 3 to Extract 11.

[Examples 1 to 20 and Comparative Examples 1 to 9]
Using the extracts shown in Table 2, aqueous preparations according to Examples 1 to 20 were obtained. In addition, Examples 3 to 20 were prepared by mixing two types of extracts in equal amounts. Moreover, the extract shown in Table 3 was made into the comparative example 1- comparative example 9, and it used for the following S. aureus enterotoxin production inhibitory effect measurement.

  About said Example 1- Example 20 and Comparative Example 1- Comparative Example 9, the Staphylococcus aureus enterotoxin production inhibitory effect was evaluated. Evaluation was performed by injecting a sample solution prepared by diluting each example into a 96-well microplate with BHI (Brain Heart Infusion Broth) medium so that the final concentration was 1.0 wt% and 2.0 wt%. Then, Staphylococcus aureus isolated from the affected skin of an atopic dermatitis patient was inoculated at 10000 cfu / mL, cultured at 35 ° C. for 20 hours, and then subjected to 1,600 rotations / minute. The supernatant was collected by centrifugation at 15 minutes, and the production of enterotoxin was confirmed based on the degree of aggregation of the sensitized latex using the reverse passive latex agglutination method (Denka Seikaken detection kit) by Aragaki et al. The results are shown in Tables 4-6.

  As is clear from Tables 4 to 6, Examples 1 to 20 of the present invention all showed an enterotoxin production inhibitory effect at a concentration of 0.25% by weight. In particular, in Examples 3, 4, 5, 6, 13, 14, 19, and 20 in which the sea vine grape extract and the hop extract, the forsythia extract, the gardenia extract, and the tomato extract were used in combination, 0.50% by weight Even when added, a high inhibitory effect on enterotoxin production was observed.

  Next, another embodiment of the present invention will be described.

  [Example 21] After Example 1 was concentrated to dryness under reduced pressure, the dried product was freeze-dried to obtain Example 21 as a powder.

  [Example 22] 80 g of soybean lecithin was added to 100 mL of Example 2, suspended at 65 ° C, and then sonicated to prepare liposomes, which were collected by centrifugation. Obtained.

  [Example 23] In Example 1, a liquid paraffin was used using a coating substance solution consisting of 0.6% by weight of sodium alginate, 12.0% by weight of polyvinyl alcohol, 12.0% by weight of glycerin and 75.4% by weight of purified water. 200 g of a microcapsule prepared by hardening a liquid paraffin with acetone as a core material and then removing the liquid paraffin with acetone, encapsulating Example 1, and then collecting by centrifugation and carrying out a microcapsule formulation. Example 23 was obtained.

  [Example 24] Atopic dermatitis exacerbation inhibitor 1 (1) Dipropylene glycol 10.0 (% by weight) (2) Carboxyvinyl polymer 0.5 (3) Potassium hydroxide 0.1 (4) Paraoxybenzoic acid Methyl 0.1 (5) Example 2 2.0 (6) Purified water 87.3 Production method: (2) is uniformly dissolved in (6), then (4) is dissolved in (1) and added. Then, (5) and (3) are sequentially added to make uniform.

  [Example 25] Atopic dermatitis exacerbation inhibitor 2 (1) Beeswaw 6.0 (wt%) (2) Cetanol 5.0 (3) Reduced lanolin 8.0 (4) Squalane 27.5 (5) Glyceryl Fatty acid ester 4.0 (6) Lipophilic glyceryl monostearate 2.0 (7) Polyoxyethylene (20E.O.) sorbitan 5.0 Monolaurate (8) 1,3-butylene glycol 5.0 (9) Methyl paraoxybenzoate 0.1 (10) Purified water 36.4 (11) Example 1 1.0 Manufacturing method: Mix and dissolve the oil phase components of (1) to (7) to 75 ° C. . On the other hand, the water phase components (8) to (10) are mixed and dissolved and heated to 75 ° C. Next, the oil phase component is added to the aqueous phase component and pre-emulsified, and then uniformly emulsified with a homomixer. After cooling, (11) is added at 40 ° C.

  [Example 26] Atopic dermatitis alleviating agent 1 Example 1 was concentrated, dried and then lyophilized. 0.2 g of the above dry powder, 52.0 g of lactose, 22.8 g of corn starch, 5.0 g of carboxymethylcellulose calcium, and 20.0 g of cellulose are mixed, granulated, and compressed to obtain a tablet of 0.2 g. Thus, oral atopic dermatitis alleviating agent 1 was obtained.

  [Example 27] Atopic dermatitis alleviating agent 2 Example 2 200 mL of simple syrup was added to 150 mL, and then purified water was added to 1.0 liter to obtain oral atopic dermatitis alleviating agent 2.

  [Example 28] Food additive 1 The solvent of Example 1 was distilled off and then lyophilized to obtain food additive 1.

  [Example 29] Food additive 2 The solvent of Example 2 was distilled off and lyophilized to obtain food additive 2.

  Clinical trials were conducted on Examples 24 to 27 of the present invention. A group of 20 patients with atopic dermatitis presenting with skin symptoms such as pruritus and skin eruption. Each group was blinded with Examples and Comparative Examples, and Examples 24 and 25 were twice daily. It was applied to the affected area for days, and Example 26 and Example 27 were taken three times a day for 3 days to evaluate the improvement status of pruritus and skin symptoms. As a comparative example, in Example 24 and Example 25, the staphylococcus aureus enterotoxin production inhibitor according to the present invention was replaced with chlorhexidine gluconate solution as Comparative Example 10, Comparative Example 11, Example 26, and Example 27. In Comparative Example 12 and Comparative Example 13, the S. aureus enterotoxin production inhibitor according to the present invention was replaced with a glucose solution. The improvement status of pruritus and skin symptom was evaluated in 4 stages of “Improved”, “Slightly improved”, “No change” and “Deteriorated”, respectively, compared with the state before starting use, and each evaluation was obtained. The panel number is shown in Table 7.

  In addition, in the above clinical trials, the flora of the skin and intestines were investigated, and the extent of the change was “○: Almost no change”, “△: Some change”, “×: Significant change” Are also shown in Table 7.

  As is clear from Table 7, in the groups used in Examples 24 and 25 of the present invention, there were no panelists who showed pruritus and worsening of skin symptoms in all groups, and an improvement tendency of these symptoms was also observed. It was. Moreover, no change was observed in the skin flora. Furthermore, in the groups taking Example 26 and Example 27, which are oral preparations, there were no panelists who showed pruritus and worsening of skin symptoms, 75% for both groups and 65% for skin symptoms. And an improvement trend was observed in 70% of panelists. No changes in intestinal flora were observed.

  On the other hand, in the use group of Comparative Examples 10 to 13, a considerable number of panelists showing a tendency to improve pruritus and skin symptoms were observed, but there were a few panelists with worsening symptoms. Furthermore, the change of skin flora was recognized remarkably. Moreover, although the change of the skin microflora was not recognized in the comparative example 12 and the comparative example 13 use group, the improvement tendency of the pruritus feeling and skin symptom was hardly recognized, and the deterioration of the symptom was recognized in 55% or more of the panelists. It was.

Next, about Example 28 and Example 29, the Staphylococcus aureus enterotoxin production inhibitory effect at the time of adding to a foodstuff was evaluated. Evaluation was carried out in a BHI medium containing 7.5 (w / v)% sodium chloride in Example 28 and Example 29 obtained by adding 200 mg and 500 mg to each 100 g of fresh cream and Japanese confectionery. After spraying 100 μL of sterile phosphate buffer containing 1.0 × 10 ⁵ CFU / mL of cultured enterotoxin-producing S. aureus ( Staphylococcus aureus ATCC14458) and allowing to stand at 37 ° C. for 10 hours, the food was homogenized, The amount of enterotoxin produced in food was measured by the RPLA method after appropriate dilution. The control to which none of the Examples was added was similarly evaluated, and the amount of enterotoxin detected in 100 g of food is shown in Table 8.

  As is apparent from Table 8, production of 20.0 μg of enterotoxin per 100 g was observed in both fresh cream and Japanese confectionery in the control, but when 500 mg of Example 28 and Example 29 of the present invention were added. The amount of enterotoxin was less than 0.6 μg, and even with the addition of 200 mg each, the amount of enterotoxin was reduced to 25% for fresh cream, 12.5% for Japanese confectionery and 6.5%. Therefore, it was shown that the food additive of the present invention can effectively prevent the occurrence of food poisoning due to contamination with Staphylococcus aureus.

  In Examples 14 to 18, no primary skin irritation and skin sensitization were observed, and oral toxicity, sensitization and teratogenicity were also observed in Examples 19 to 22. I couldn't. In Examples 1 to 22 of the present invention, even when stored at 25 ° C. for 6 months, no change in the state of the preparation was observed, and no reduction in S. aureus enterotoxin production inhibitory effect was observed.

Claims (5)

A S. aureus enterotoxin production inhibitor comprising a sea urchin grape extract. Further, hop (Humulus lupulus L.), Forsythia (Forsythia suspensa Vahl), Sina Forsythia (Forsythia viridissima Lindl.), Korean Forsythia (Forsythia koreana Nakai), tow calendula (Calendula officinalis L.), calendula (Calendula arvensis L.) , Honeysuckle ( Lonicera japonica Thunb.), Lonicera gracilipes Miq. Var. Glabra Miq., Salvia ( Salvia officinalis L.) and its varieties, Gardenia jasminoides Ellis and its genus plants, Sasa veitchii Rehd .), Nettle ( Urtica thunbergiana Sieb. Et Zucc.), Myrtle Laxea ( Laportea macrostachya Ohwi), Tokikoshi ( Isodon japonicus Hara), and one or more plant extracts selected from Isodon trichocarpus Kudo Inhibition of Staphylococcus aureus enterotoxin production according to claim 1, which is used in combination. Agent. An atopic dermatitis exacerbation preventing or alleviating agent comprising the S. aureus enterotoxin production inhibitor according to claim 1 or 2. A food poisoning preventive agent comprising the S. aureus enterotoxin production inhibitor according to claim 1 or 2. A food additive comprising the S. aureus enterotoxin production inhibitor according to claim 1 or 2.