Anti-type IV allergy agents and compositions for anti-type IV allergies

Abstract

To provide an anti-type IV allergy agent and a composition for anti-type IV allergies that have excellent anti-type IV allergy activity and high safety. [Solution] This is an anti-type IV allergy agent containing the cells of Lactobacillus plantarum strain 22A-3 (FERM BP-21411).

Description

Technical Field

[0001] The present invention relates to an anti-Type IV allergy agent and a composition for anti-Type IV allergy.

Background Art

[0002] Type IV allergy, also called delayed-type allergy, is tissue damage caused by sensitized T cells that specifically react with an antigen. Diseases of Type IV allergy include contact dermatitis, drug eruption, atopic dermatitis, and rarely, an immune reaction against a transplanted organ after organ transplantation. The onset of allergic inflammation induced by chemicals and the like results in a decrease in the quality of life (QOL) in daily life.

[0003] So far, an oral anti-allergy agent containing fucoxanthin, its derivative or its salt as an active ingredient, which can be applied to Type I allergy and / or Type IV allergy, has been proposed (see, for example, Patent Document 1).

Prior Art Documents

Patent Documents

[0004] <​​​​​​​​​​​​​​​​The present invention aims to solve the aforementioned conventional problems and achieve the following objectives. Specifically, the present invention aims to provide an anti-type IV allergy agent and an anti-type IV allergy composition that have excellent anti-type IV allergy activity and high safety. [Means for solving the problem]

[0007] In order to solve the aforementioned problems, the inventors conducted extensive research and discovered that Lactobacillus plantarum strain 22A-3 (FERM BP-21411), which has high safety, possesses excellent anti-type IV allergic activity.

[0008] The present invention is based on the inventors' aforementioned findings, and the means for solving the aforementioned problems are as follows: <1> This is an anti-type IV allergy agent characterized by containing the cells of Lactobacillus plantarum strain 22A-3 (FERM BP-21411). <2> The aforementioned <1> This is an anti-type IV allergy composition characterized by containing the anti-type IV allergy agent described above. [Effects of the Invention]

[0009] According to the present invention, it is possible to solve the aforementioned problems in the conventional era, achieve the aforementioned objectives, and provide an anti-type IV allergy agent and an anti-type IV allergy composition that have excellent anti-type IV allergy activity and high safety. [Brief explanation of the drawing]

[0010] [Figure 1] Figure 1 is a graph showing the measurement results of auricle swelling in Test Example 1. [Figure 2] Figure 2 is a graph showing the measurement results of the distribution of pro-inflammatory macrophages (M1) in Test Example 1. [Figure 3]Figure 3 is a graph showing the measurement results of the distribution of anti-inflammatory macrophages (M2) in Test Example 1. [Modes for carrying out the invention]

[0011] (Anti-type IV allergy medication) The anti-type IV allergy agent of the present invention contains at least the cells of Lactobacillus plantarum strain 22A-3 (FERM BP-21411), and further contains other components as needed.

[0012] In this specification, anti-type IV allergic effect means preventing or improving type IV allergic reactions or type IV allergic diseases.

[0013] The aforementioned prevention includes, for example, suppressing, reducing, or mitigating the occurrence of a type IV allergic reaction or the development of a type IV allergic disease. The aforementioned prevention includes not only completely preventing the occurrence of a type IV allergic reaction or the development of a type IV allergic disease, but also reducing the severity of any type IV allergic reaction that occurs or the severity of any type IV allergic disease that develops. Furthermore, the aforementioned prevention also includes preventing the worsening of any type IV allergic reaction that occurs or any type IV allergic disease that develops.

[0014] The aforementioned improvements include, for example, reducing or mitigating the severity of the type IV allergic reaction that occurred or the type IV allergic disease that developed. The aforementioned reduction or mitigation includes not only complete recovery from the type IV allergic reaction that occurred or the type IV allergic disease that developed, but also partial recovery.

[0015] There are no particular restrictions on the types of allergic diseases that can be treated with type IV allergies; they can be selected appropriately depending on the purpose. Examples include contact dermatitis, drug eruptions, atopic dermatitis, and immune reactions to transplanted organs after organ transplantation.

[0016] <Cells of Lactobacillus plantarum 22A-3 strain (FERM BP-21411)> It has been completely unknown in the past that the cells of Lactobacillus plantarum 22A-3 strain (hereinafter sometimes referred to as "LP22A-3 strain") have an anti-Type IV allergy effect and are useful as an active ingredient of an anti-Type IV allergy agent, which is a new finding by the present inventors.

[0017] The LP22A-3 strain is a strain isolated and identified by the applicant from pickles, has tannase activity, does not have gallic acid decarboxylase activity, and has inulin assimilation ability.

[0018] The LP22A-3 strain was deposited and accepted by the applicant Maruzen Pharmaceutical Co., Ltd. (No. 10, 14703-1, Mukaecho, Onomichi City, Hiroshima Prefecture) in Japan on October 22, 2007. Thereafter, on May 31, 2023, the applicant filed a request for transfer to an international deposit under the Budapest Treaty and was accepted by the Patent Biological Depositary, National Institute of Technology and Evaluation (Room 120, 2-5-8 Kazusa Kamashima, Kisarazu City, Chiba Prefecture) under the accession number FERM BP-21411.

[0019] There is no particular limitation on the culturing method of the LP22A-3 strain, and known culturing methods for lactic acid bacteria can be appropriately selected.

[0020] There is no particular limitation on the medium used for culturing the LP22A-3 strain, and a medium usually used for culturing lactic acid bacteria or a modified medium thereof can be used. Examples of the medium components incorporated into the medium include carbon sources such as glucose; nitrogen sources such as yeast extract, meat extract, casein, and protein hydrolysates thereof; inorganic salts such as sodium chloride, sodium phosphate, potassium phosphate, ammonium citrate, and magnesium sulfate; and vitamins such as thiamine and inositol, which are components suitable for the growth of lactic acid bacteria.

[0021] There are no particular restrictions on the culture conditions for culturing the LP22A-3 strain, such as the pH of the culture medium, culture temperature, culture time, and culture method, and known conditions can be appropriately selected. For example, the culture temperature is preferably 25 to 45°C, and more preferably 30 to 37°C. The culture time is preferably 4 to 74 hours, and more preferably 18 to 48 hours. Examples of culture methods include standing, stirring, shaking, and aeration.

[0022] There are no particular restrictions on the form of the LP22A-3 strain cells, and they can be appropriately selected according to the purpose. The culture containing the cells (sometimes referred to as the "fermented product") may be used as is, or cells isolated from the culture may be used.

[0023] There are no particular restrictions on the method for isolating the LP22A-3 strain from the culture, and any known method can be appropriately selected, such as centrifugation or filtration.

[0024] The bacterial cells of strain LP22A-3 may be concentrated or dried as needed.

[0025] The LP22A-3 strain may be used as either live or dead cells. Alternatively, live and dead cells may be used in combination.

[0026] Because the LP22A-3 strain has excellent anti-type IV allergic activity, it can be used as an active ingredient in anti-type IV allergy agents.

[0027] The anti-type IV allergy agent may consist solely of the bacterial cells of the LP22A-3 strain, or it may be a formulation of the bacterial cells of the LP22A-3 strain.

[0028] The bacterial cells of strain LP22A-3 can be formulated into any dosage form, such as powder, granules, tablets, or liquid, according to conventional methods, using pharmaceutically acceptable carriers such as dextrin or cyclodextrin, or other optional auxiliary agents. In this case, auxiliary agents such as excipients, binders, disintegrants, lubricants, stabilizers, and flavoring / odorizing agents can be used.

[0029] The aforementioned anti-type IV allergy agent can be used in combination with other compositions (for example, the anti-type IV allergy composition described later), and can also be used as oral preparations such as tablets, powders, capsules, granules, extracts, and syrups; parenteral preparations such as injections, drips, and suppositories; and as ointments, eye drops, topical solutions, and patches.

[0030] There are no particular restrictions on the amount of LP22A-3 strain cells contained in the formulated anti-type IV allergy agent; it can be appropriately selected depending on the purpose. For example, the number of LP22A-3 strain cells may be 1.0 × 10⁶. 7 ~1.0×10 13 Examples include pieces / gram.

[0031] <Other ingredients> The aforementioned other components are not particularly limited as long as they do not impair the effects of the present invention, and can be appropriately selected depending on the form of use of the anti-type IV allergy agent, for example, components that can be used when formulating as described above. The aforementioned other components may be used alone or in combination of two or more.

[0032] There are no particular restrictions on the content of the other components in the anti-type IV allergy agent, and they can be appropriately selected depending on the purpose.

[0033] There are no particular restrictions on the method of use of the aforementioned anti-type IV allergy agent, and it can be appropriately selected according to the purpose. Examples include oral administration, parenteral administration, and topical application, but oral administration is preferred.

[0034] There are no particular restrictions on the dosage form of the aforementioned anti-type IV allergy agent; known dosage forms can be appropriately selected according to the purpose.

[0035] There are no particular restrictions on the method for producing the anti-type IV allergy agent, and known methods can be appropriately selected depending on the dosage form.

[0036] There are no particular restrictions on the dosage, site of administration, duration of administration, or interval between administrations of the aforementioned anti-type IV allergy agent (hereinafter sometimes referred to as "dosage, site of administration, duration of administration, and interval between administrations"), and these can be appropriately selected according to the purpose.

[0037] There are no particular restrictions on the amount of the aforementioned anti-type IV allergy agent used (hereinafter sometimes referred to as "ingestion amount"), and it can be appropriately selected according to the purpose. For example, the number of LP22A-3 strain bacteria may be 1.0 × 10 per day. 7 ~1.0×10 13 Examples include individuals. There are no particular restrictions on the amount of the anti-type IV allergy agent used, and it can be appropriately selected depending on the amount of LP22A-3 strain bacteria contained in the anti-type IV allergy agent.

[0038] The aforementioned anti-type IV allergy agent is highly safe and can be used on a daily basis. For example, it may be used preventively to prevent type IV allergic reactions or type IV allergic diseases, or it may be used to improve type IV allergic reactions that have occurred or type IV allergic diseases that have developed. There are no particular restrictions on the frequency of use, and it can be appropriately selected according to the purpose. For example, it may be administered once a day or in divided doses depending on the age, sex, and severity of allergic symptoms of the recipient, or it may be administered continuously for several days, several weeks, or several months.

[0039] The anti-type IV allergy agent can prevent or improve type IV allergic reactions or type IV allergic diseases through the excellent anti-type IV allergy activity of the LP22A-3 strain of bacteria. The anti-type IV allergy agent can be used in all applications where exhibiting anti-type IV allergy activity is significant.

[0040] The anti-type IV allergy agent can be used in a wide range of applications, including pharmaceuticals, quasi-drugs, oral compositions, cosmetics, and reagents for research on the mechanism of action of anti-type IV allergies. For example, the anti-type IV allergy agent can be suitably used as an ingredient in the anti-type IV allergy composition described later. In this case, the LP22A-3 strain cells may be incorporated as they are, or a formulation of the LP22A-3 strain cells may be incorporated.

[0041] Furthermore, the aforementioned anti-type IV allergy agent may, if necessary, be used as an active ingredient by combining it with other components having anti-type IV allergy activity together with the LP22A-3 strain of bacteria.

[0042] The aforementioned anti-type IV allergy agent is suitably applied to humans, but can also be applied to animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cattle, pigs, monkeys, etc.) as long as its effects are achieved.

[0043] (Anti-type IV allergy composition) The anti-type IV allergy composition of the present invention comprises at least the anti-type IV allergy agent of the present invention, and optionally other components.

[0044] <Anti-type IV allergy medication> The aforementioned anti-type IV allergy agent is the anti-type IV allergy agent of the present invention described above.

[0045] There are no particular restrictions on the content of the anti-type IV allergy agent in the anti-type IV allergy composition, and it can be appropriately adjusted depending on the form of the anti-type IV allergy composition. For example, if the intake of the LP22A-3 strain is 1.0 × 10⁶ per day in terms of bacterial count... 7 ~1.0×10 13 Examples include setting the content to such an extent that it is equivalent to one unit. The anti-type IV allergy composition may consist solely of the anti-type IV allergy agent.

[0046] <Other ingredients> Other components in the aforementioned anti-type IV allergy composition are not particularly limited and can be appropriately selected depending on the form of use of the anti-type IV allergy composition. Examples include those similar to the other components listed in the "anti-type IV allergy agent" section above. These may be used individually or in combination of two or more.

[0047] There are no particular restrictions on the content of the other components in the anti-type IV allergy composition, and they can be appropriately selected depending on the purpose.

[0048] <Nature> The embodiments of the anti-type IV allergy composition are not particularly limited and can be appropriately selected depending on the purpose. Examples include pharmaceuticals, quasi-drugs, oral compositions, cosmetics, and reagents for research on the mechanism of action of anti-type IV allergies.

[0049] The anti-type IV allergy composition of the present invention is highly safe and can be used on a daily basis. Through the action of the LP22A-3 strain, which is the active ingredient, it can exert various physiologically active effects, including anti-type IV allergy activity, very effectively.

[0050] The aforementioned anti-type IV allergy composition is suitably applied to humans, but can also be applied to animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cattle, pigs, monkeys, etc.) as long as its effects are achieved.

[0051] There are no particular restrictions on the use of the aforementioned anti-type IV allergy composition, and the method can be appropriately selected depending on the purpose. Examples include oral administration, parenteral administration, and topical application, but oral administration is preferred.

[0052] The aforementioned oral composition is not particularly limited and can be appropriately selected depending on the purpose, and examples include oral preparations and food and beverages. Here, "food and beverages" refers to items that are unlikely to pose a risk to human health and are ingested orally or through the gastrointestinal tract in normal social life, and is not limited to administrative classifications such as food, pharmaceuticals, or quasi-drugs. Therefore, "food and beverages" broadly includes general foods, health foods (functional foods and beverages), health functional foods (foods for specified health uses, nutrient function foods, foods with functional claims), quasi-drugs, pharmaceuticals, etc., that are ingested orally.

[0053] There are no particular restrictions on the type of oral composition, and it can be appropriately selected according to the purpose. Examples include: beverages such as tea beverages, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, alcoholic beverages, coffee beverages, and coffee-flavored soft drinks (including concentrated stocks and powders for adjusting these beverages); frozen desserts such as ice cream, ice sherbet, and shaved ice; noodles such as soba, udon, vermicelli, dumpling wrappers, shumai wrappers, Chinese noodles, and instant noodles; confectionery such as candy, candy, gummy candy, gum, chocolate, tablets, snacks, biscuits, cookies, jelly, jam, cream, baked goods, and bread; marine products such as crab, salmon, clams, tuna, sardines, shrimp, bonito, mackerel, whale, oysters, saury, squid, ark clams, scallops, abalone, sea urchin, salmon roe, and ear shells; and kamaboko (a type of shellfish). Examples of processed seafood and livestock products include: dried fish, ham, sausages, and other processed seafood and livestock products; dairy products such as processed milk and fermented milk; oils and fats and processed oils such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings; seasonings such as sauces and dips; soups such as curry, stew, oyakodon, porridge, zousui, chukadon, katsudon, tempuradon, unadon, hayashi rice, oden, mapo tofu, gyudon, meat sauce, and egg soup; retort pouch foods such as omurice, gyoza, shumai, hamburgers, and meatballs; prepared foods such as salads and pickles; health, beauty, and nutritional supplements in various forms; pharmaceuticals and quasi-drugs such as tablets, powders, capsules, granules, extracts, syrups, drinks, lozenges, and mouthwashes; and oral fresheners and toothpastes used in the mouth, such as mouth fresheners and bad breath preventatives.

[0054] There are no particular limitations on the method for producing the anti-type IV allergy composition, and it can be appropriately selected depending on the form of the anti-type IV allergy composition.

[0055] There are no particular restrictions on the amount, duration, or interval of use of the aforementioned anti-type IV allergy composition, and these can be appropriately selected according to the purpose. For example, they can be the same as those of the anti-type IV allergy agents described above.

[0056] As described above, the anti-type IV allergy agent and anti-type IV allergy composition of the present invention have excellent anti-type IV allergy activity. Therefore, the present invention also relates to a method for preventing or improving a type IV allergic reaction or a disease of type IV allergy, characterized by administering at least one of the anti-type IV allergy agent and the anti-type IV allergy composition to an individual. Furthermore, the present invention also relates to the use of the Lactobacillus plantarum 22A-3 strain (FERM BP-21411) for use in the prevention or improvement of type IV allergic reactions or type IV allergic diseases.

[0057] Furthermore, as shown in the test examples described later, the Lactobacillus plantarum 22A-3 strain (FERM BP-21411) has been shown to reduce pro-inflammatory macrophages (M1) and increase anti-inflammatory macrophages (M2 macrophages).

[0058] Therefore, the present invention relates to: an inhibitor of differentiation into pro-inflammatory macrophages characterized by comprising the cells of Lactobacillus plantarum strain 22A-3 (FERM BP-21411); a composition for inhibiting differentiation into pro-inflammatory macrophages characterized by comprising the inhibitor of differentiation into pro-inflammatory macrophages; a method for inhibiting differentiation into pro-inflammatory macrophages characterized by administering at least one of the inhibitor of differentiation into pro-inflammatory macrophages and the composition for inhibiting differentiation into pro-inflammatory macrophages to an individual; and the use of the cells of Lactobacillus plantarum strain 22A-3 (FERM BP-21411) for use in inhibiting differentiation into pro-inflammatory macrophages.

[0059] The present invention also relates to a promoter for promoting differentiation into anti-inflammatory macrophages, which comprises cells of Lactobacillus plantarum strain 22A-3 (FERM BP-21411); a composition for promoting differentiation into anti-inflammatory macrophages, which comprises the promoter for promoting differentiation into anti-inflammatory macrophages; a method for promoting differentiation into anti-inflammatory macrophages, which comprises administering at least one of the promoter for promoting differentiation into anti-inflammatory macrophages and the composition for promoting differentiation into anti-inflammatory macrophages to an individual; and use of the cells of Lactobacillus plantarum strain 22A-3 (FERM BP-21411) for use in promoting differentiation into anti-inflammatory macrophages.

Example

[0060] Hereinafter, test examples and formulation examples of the present invention will be described, but the present invention is not limited to these test examples and formulation examples in any way.

[0061] (Test Example 1) The effect of Lactobacillus plantarum strain 22A-3 (FERM BP-21411) (hereinafter sometimes referred to as "LP22A-3 strain") on allergic dermatitis (contact dermatitis) caused by type IV (delayed type) allergy was tested as follows.

[0062] [Test method] <Administration of LP22A-3 strain> LP22A-3 strain was suspended in distilled water and then autoclaved (121 °C, 15 minutes). The autoclaved LP22A-3 strain was orally administered to C57BL / 6 mice (5 mice / group) for 3 weeks. The daily dose of LP22A-3 strain was 1×10 8 cells / mouse.

[0063] <Induction of allergic dermatitis (contact dermatitis)> Using dinitrofluorobenzene (DNFB) as an antigen, allergic dermatitis was induced as follows. The hair on the chest of the mice was shaved, and 50 μL of 0.5% DNFB solution (DNFB dissolved in a solvent (acetone:olive oil = 4:1)) was dropped onto each mouse. This sensitization was performed twice, on day 15 and day 16 of administration of the LP22A-3 strain. The control group received only the solvent (acetone:olive oil = 4:1). On days 21 and 22 of administration of the LP22A-3 strain, 20 μL of 0.5% DNFB solution was dropped onto the dorsal portion of the auricle (both ears) to induce swelling (edema) of the auricle. In addition, to confirm that the dermatitis induced by DNFB was a type IV (delayed-type) allergic reaction, a test group was prepared in which only the auricle was challenged without sensitization of the chest.

[0064] [Measurement of auricle swelling] The swelling of the auricle was determined by subtracting the thickness of the auricle immediately before the administration on day 21 from the thickness of the auricle 24 hours after the administration on day 22.

[0065] [Effects of administration of LP22A-3 strain on macrophage differentiation] The effect of the LP22A-3 strain on macrophage differentiation in C57BL / 6 mice with induced contact dermatitis was measured and analyzed using FACS (fluorescence-activated cell sorting). Mice were euthanized under isoflurane inhalation anesthesia 24 hours after the administration on day 22, and macrophages were collected from the peritoneal cavity. CD86 was used as a macrophage differentiation marker for pro-inflammatory macrophages (M1), and CD206 was used for anti-inflammatory macrophages (M2). These were detected and measured using a flow cytometer with fluorescently labeled antibodies against these markers.

[0066] [result] The measurement results (average values) for auricle swelling are shown in Table 1 and Figure 1.

[0067] [Table 1]

[0068] To confirm that this allergic reaction was delayed-type, the thickness of the auricle was measured when the antigen (DNFB) was applied only to the auricle without antigen sensitization to the chest ("Auricle-only antigen application group," labeled "(4)" in Table 1 and Figure 1). As a result, no significant difference was observed compared to the control group that did not receive antigen stimulation (labeled "(1)" in Table 1 and Figure 1), confirming that this allergic reaction was delayed-type.

[0069] As shown in Table 1 and Figure 1, the group in which contact dermatitis was induced and administered the LP22A-3 strain ("Dermatitis Induction and LP22A-3 Strain Administration Group," labeled "(3)" in Table 1 and Figure 1) showed a significantly suppressed increase in auricle thickness compared to the group in which contact dermatitis was induced but the LP22A-3 strain was not administered ("Dermatitis Induction Group," labeled "(2)" in Table 1 and Figure 1).

[0070] Tables 2 and 3, and Figures 2 and 3, show the results of an investigation into the effects of LP22A-3 strain administration on macrophage differentiation. Table 2 and Figure 2 show the distribution of pro-inflammatory macrophages (M1), while Table 3 and Figure 3 show the distribution of anti-inflammatory macrophages (M2).

[0071] [Table 2]

[0072] [Table 3]

[0073] As shown in Tables 2 and 3 and Figures 2 and 3, in the group in which contact dermatitis was induced and administered the LP22A-3 strain ("Dermatitis Induction / LP22A-3 Strain Administration Group," labeled "(3)" in Tables 2 and 3 and Figures 2 and 3), a decrease in pro-inflammatory macrophages (M1), which had increased significantly due to the allergic reaction, and a significant increase in anti-inflammatory macrophages (M2) were observed.

[0074] However, in the group that received only LP22A-3 strain ("LP22A-3 strain administered group (antigen-insensitive)", indicated as "(5)" in Tables 2 and 3 and Figures 2 and 3), there was no significant difference compared to the control group that did not receive antigen stimulation (indicated as "(1)" in Tables 2 and 3 and Figures 2 and 3), suggesting that administration of LP22A-3 strain does not directly affect macrophage differentiation.

[0075] These results suggest that ingestion of the LP22A-3 strain confers resistance to the induction of allergic responses. This is thought to have suppressed the development of allergic dermatitis (contact dermatitis). Therefore, it was confirmed that the LP22A-3 strain exhibits anti-type IV allergic activity.

[0076] (Combination example 1) Tablets (daily dose) with the following composition were manufactured by conventional methods. • LP22A-3 strain-containing preparation 20.0 mg (Smart Lactobacillus® Powder (manufactured by Maruzen Pharmaceutical Co., Ltd.)) Dolomite 83.4mg (Contains 20% calcium and 10% magnesium) Casein phosphopeptide 16.7 mg • Vitamin C 33.4mg • Maltitol 136.8mg • Collagen 12.7mg • Sucrose fatty acid ester 12.0 mg

[0077] (Combination example 2) An oral liquid preparation (daily dose) having the following composition was manufactured by conventional methods. <Composition per ampoule (100 mL)> • Preparation containing LP22A-3 strain: 0.04% by mass (Smart Lactobacillus (registered trademark) dead bacteria MF (manufactured by Maruzen Pharmaceutical Co., Ltd.)) • Sorbitol 12.0% by mass • Sodium benzoate 0.1% by mass · Fragrance 1.0% by mass • Calcium sulfate 0.5% by mass · Purified water remainder

[0078] (Combination example 3) A soft drink (daily intake) with the following composition was manufactured using conventional methods. • LP22A-3 strain-containing preparation 0.02g (Smart Lactobacillus® Powder (manufactured by Maruzen Pharmaceutical Co., Ltd.)) • Royal jelly 3.0g • Water-soluble collagen 8.0g • Job's Tears Extract 1.0g • Korean ginseng extract 1.0g • Placenta extract 1.0g • Pueraria extract 1.0g • Purple yam extract 1.0g • Oligosaccharide 5.0g • Sucrose 10.0g • Prune juice 2.0g • Pomegranate juice 5.0g • Grapefruit juice 10.0g • Vitamin C 1.0g • Grapefruit flavor 1.0g • Water remaining (assuming the total amount is 100g)

[0079] (Combination example 4) A capsule preparation (daily dose) with the following composition was manufactured using a conventional method. A No. 1 hard gelatin capsule was used as the capsule. <Composition per capsule> • Preparation containing LP22A-3 strain, 40.0 mg (Smart Lactobacillus (registered trademark) dead bacteria MF (manufactured by Maruzen Pharmaceutical Co., Ltd.)) • Corn starch 70.0 mg · Lactose 80.0mg • Calcium lactate 10.0 mg • Hydroxypropylcellulose (HPC-L) 10.0 mg [Accession Number]

[0080] FERM BP-21411

Claims

1. An anti-type IV allergy agent characterized by containing the bacterial cells of Lactobacillus plantarum strain 22A-3 (FERM BP-21411).

2. An anti-type IV allergy composition characterized by containing the anti-type IV allergy agent described in claim 1.

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