Tumor suppressor

Abstract

Provided is a tumor suppressor containing a composition that is capable of sufficiently exhibiting a tumor suppression effect while suppressing side effects. The tumor suppressor contains, as the composition, cholera toxins and a lactic acid bacterium culture as active ingredients, and the lactic acid bacterium culture may contain three types of cultures that are Lactobacillus fermentum, Lactobacillus subtilis, and Actinomycete SIID11972.

Description

Tumor suppressors

[0001] The present invention relates to a mixed bacterial tumor suppressor.

[0002] In recent years, some antitumor agents with antiviral effects have been found to have strong side effects, limiting their use. Given these issues, the development of antitumor agents with fewer side effects remains a major challenge. One of the reasons for the difficulty in developing antitumor agents with fewer side effects is the close relationship between pharmacological efficacy and side effects, with suppression of side effects leading to suppression of pharmacological efficacy. Examples of side effect suppressors that act on known antitumor agents include amifostine for cisplatin, potassium oxonate for 5-fluorouracil, and combinations of cisplatin, cyclophosphamide, or doxorubicin hydrochloride with chromanol glycosides. While these antitumor agents are effective in inhibiting tumors, due to the characteristics of tumor cells, some strains are inherently resistant to the drugs used, and these resistant strains easily acquire resistance to the antitumor agents. Therefore, in order to achieve effective tumor suppression, it is usually necessary to select and use multiple antitumor agents in combination, which is not conclusive for effective treatment with fewer side effects (see, for example, Patent Documents 1 and 2).

[0003] Furthermore, known examples of drugs that can exert a tumor-suppressing effect and suppress side effects include an immune-stimulating composition containing a mixed culture of 3 to 8 species of lactic acid bacteria selected from the group consisting of Lactobacillus delbrueckii, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus casei, Lactobacillus rhamnosus, Lactococcus lactis, and Streptococcus thermophilus with Saccharomyces cerevisiae, or a mixed bacterial cell or culture supernatant derived from the mixed culture (see, for example, Patent Document 3).

[0004] Also known is a tumor inhibitor, which is prepared by forming multiple groups using lactic acid bacteria from three genera, namely, Lactobacillus, Bifidobacterium, and Streptococcus, and maintaining a symbiotic state using one or more lactic acid bacteria selected from these three genera, subculturing each group to maintain a symbiotic state, and further co-culturing the subcultured lactic acid bacteria from each group to obtain a lactic acid bacteria culture solution, heat-sterilizing the lactic acid bacteria, filtering the filtrate, and mixing the powdered residue obtained by filtering the filtrate (see, for example, Patent Document 4). However, as mentioned above, these drugs may not be definitive for treatments aimed at suppressing tumors and side effects.

[0005] Japanese Patent No. 2614164 Japanese Patent No. 4509574 Japanese Patent Laid-Open No. 2005-068092 Japanese Patent Laid-Open No. 2005-097280

[0006] The technology disclosed herein has been made in consideration of the above circumstances, and its purpose is to provide a tumor inhibitor containing a composition that can fully exert its tumor-inhibiting effect while suppressing side effects.

[0007] The present disclosure provides a tumor inhibitor comprising a cholera toxin and a lactic acid bacteria culture as active ingredients. The lactic acid bacteria culture may contain Lactobacillus fermentum, Lactobacillus subtilis, and Actinomycete SIID11972.

[0008] Cholera toxins, when ingested, exert pharmacological effects against various diseases, including muscular dystrophy and diabetes, and also exhibit tumor-suppressing effects. However, they also have strong side effects, specifically, cytotoxicity, organ damage, and decreased immune function may occur after ingestion of cholera toxins. In contrast, lactic acid bacteria cultures are compositions that are also contained in foods and have the effect of suppressing the side effects of cholera toxins. That is, tumor inhibitors containing cholera toxins and lactic acid bacteria cultures as active ingredients can simultaneously suppress tumors and the associated side effects. In particular, the effect of suppressing side effects is significantly enhanced when the lactic acid bacteria culture contains a triple culture of Lactobacillus fermentum, Lactobacillus subtilis, and Actinomycete SIID11972 as active ingredients. Furthermore, when the lactic acid bacteria culture contains Lactobacillus fermentum as the main component among the three cultures, the effect of suppressing side effects is even more pronounced.

[0009] In the present disclosure, the lactic acid bacteria culture may be composed of Lactobacillus fermentum, skim milk powder, natural salt, molasses, monosodium glutamate, potato starch, and defatted soy flour. Specifically, the lactic acid bacteria culture may be composed of 1.5% Lactobacillus fermentum culture solution, 4% skim milk powder, 1.5% natural salt, 1% molasses, 0.5% monosodium glutamate, 6% potato starch, 7% defatted soy flour, and 100% (by weight) purified water. After culturing for 48 hours at 40°C, the mixture is slurried using a mixer, and then dried using a spray dryer at an inlet temperature of 150°C and an outlet temperature of 75°C to obtain a dry powder of the lactic acid bacteria culture. Mixing the dry powder of the lactic acid bacteria culture thus obtained with cholera toxins can simultaneously suppress tumor growth and the associated side effects, as described above. Furthermore, a dry powder of a lactic acid bacteria culture can be easily produced by the above-mentioned method.

[0010] In the present disclosure, the Lactobacillus fermentum may be NBRC 3071 or a metabolic derivative of NBRC 3071. NBRC 3071 is a known microorganism, and its dried form can be easily obtained. Furthermore, metabolic derivatives of NBRC 3071 can be easily obtained by, for example, acclimatization in an extreme environment, UV irradiation, chemical treatment, or genetic recombination.

[0011] In addition, in the present disclosure, the tumor inhibitor may be formulated as tablets, granules, or capsules by mixing with at least one of dextrin, starch, gum arabic, lactose, sucrose, crystalline cellulose, carboxymethylcellulose, methylcellulose, stearates, talc, and anhydrous silicic acid. This allows the tumor inhibitor to be ingested into the body by oral administration. For example, parenteral administration such as injection may result in only a localized tumor inhibitory effect, whereas oral administration allows the tumor inhibitory effect to be distributed throughout the body. Furthermore, oral administration can be performed by a single person, for example, at home, and does not require special medical equipment such as a syringe, making it relatively easy and inexpensive to administer.

[0012] The above means for solving the problems can be used in combination with each other whenever possible.

[0013] According to the technology disclosed herein, it is possible to fully exert the effect of suppressing tumors while suppressing side effects.

[0014] [Embodiment 1] A tumor inhibitor according to embodiment 1 of the present disclosure will be described below. Note that the tumor inhibitor according to embodiment 1 of the present disclosure is not intended to be limited to the following configuration.

[0015] The tumor inhibitor of embodiment 1 contains cholera toxins and a lactic acid bacteria culture as active ingredients. The lactic acid bacteria culture contains a triple culture of Lactobacillus fermentum, Lactobacillus subtilis, and Actinomycete SIID11972 as active ingredients. Cholera toxins are proteinaceous compounds composed of a heterohexamer with a molecular weight of approximately 84,000, consisting of one subunit with a molecular weight of approximately 27,000 and five subunits with a molecular weight of approximately 11,600. Cholera toxins have pharmacological effects against various diseases, including muscular dystrophy and diabetes, and also have tumor-suppressing effects. The mechanism of action relies on cAMP accumulation via ADP-ribosylation of Gs protein within tumor cells and induction of tumor cell differentiation via binding of the approximately 11,600 molecular weight subunit to ganglioside GM1 on the tumor cell surface. Cholera toxins can be produced, for example, from products of Vibrio cholerae as raw materials, or can be produced using techniques such as genetic recombination.

[0016] On the other hand, the lactic acid bacteria culture containing the triple culture of Lactobacillus fermentum, Lactobacillus subtilis, and Actinomycete SIID11972 as active ingredients has the effect of suppressing the side effects caused by cholera toxins. That is, by containing cholera toxins and lactic acid bacteria culture as active ingredients, the tumor inhibitor can fully exert the effect of tumor suppression while suppressing side effects. In addition, by containing the above triple culture as active ingredients, the effect of suppressing side effects can be further improved. In addition, lactic acid bacteria culture can also be used for food, and is highly safe when ingested.

[0017] In addition, Lactobacillus fermentum is an anaerobic bacterium, while Lactobacillus subtilis and Actinomycete SIID11972 are aerobic bacterium.Therefore, by the symbiosis of these three cultures, Lactobacillus subtilis and Actinomycete SIID11972 can absorb the oxygen released by Lactobacillus fermentum.Therefore, for tumor inhibitors, Lactobacillus subtilis and Actinomycete SIID11972 can maintain an active state without dormancy even in an anoxic environment such as the human intestine.

[0018] The cultivation process for Lactobacillus fermentum is described below. First, molten agar is poured into a Petri dish (circular glass container) to form a BCP plate count agar medium, and the Lactobacillus fermentum strain is applied to a 2 mm thick layer with a platinum rod. The Petri dish with the Lactobacillus fermentum strain is then placed in an incubator and cultured at a constant temperature of 37°C for 24 hours, then placed in a 20 L Baron box. Next, 1 L of distilled water is placed in a 2 L wide-mouth bottle and mixed with 5 g of yeast, 5 g of glucose, and 5 g of peptone. The resulting mixture is then placed in an autoclave and sterilized at a constant temperature of 120°C for 20 minutes, after which it is cooled to below 40°C to produce a culture solution.

[0019] Next, place this culture solution into a 20L Baron box and add 100g of propagation material (such as soybean powder), 200g of starch (such as potato starch), 100g of blackstrap molasses, 400g of trehalose, 200g of skim milk, and 10mL of purified water to make a 1000mL mixture. Next, immerse the Baron box containing this mixture in 37°C warm water for 48 hours, then remove the Baron box and allow it to degas. Next, dry the mixture using a heat storage drying method and then transfer it to a stainless steel tray.

[0020] Next, the mixed solution in the stainless steel tray is dried at 37°C for 48 to 52 hours, allowing the water to evaporate gradually until the moisture content is 8% or less. Finally, the dried mixture is mixed and sieved through a mesh.

[0021] Next, we will explain the culture process for Lactobacillus subtilis. Lactobacillus subtilis is a species of Bacillus subtilis (a type of natto fungus). First, commercially available natto was placed in a 2L wide-mouth jar and soaked in 1000mL of purified water. It was then mixed with 5g of peptone, 5g of extra yeast, and 5g of glucose. The resulting mixture was then placed in an autoclave and boiled at 120°C for 20 minutes, then cooled. An additional 5g of natto was added and placed in an incubator for 24 hours at 37°C. The resulting culture was then filtered through filter paper. 1000mL of the filtered culture was placed in a 20L Baron box, and 1000g of Soyafit, 200g of skim milk, 200g of starch (potato starch, etc.), 400g of trehalose, and 200g of the unfiltered culture broth were added and cultured for 48 hours. The mixture was then transferred to a stainless steel tray.

[0022] Next, the mixed solution is placed in a stainless steel tray and dried at 37°C for 52 hours, gradually evaporating the water until the moisture content is below 8%. This eliminates the ammonia odor emitted from the mixed solution. Finally, the dried mixture is mixed and sieved through a mesh.

[0023] Next, we will explain the cultivation process for actinomycete SIID11972. First, commercially available pineapples are peeled, finely chopped, and dried in the sun. This sun-drying process allows the actinomycete SIID11972 to grow in the pineapple skin as a culture medium. Next, the sun-dried pineapple skin is crushed in a blender, and 50 g of the crushed skin is placed in a 2 L wide-mouth bottle and immersed in 1000 mL of purified water to produce a culture solution. Next, the actinomycete SIID11972 is placed in an incubator at 37°C and allowed to grow and proliferate for 24 hours to produce an inoculum of actinomycete SIID11972. The resulting inoculum is filtered using filter paper, and then 10 L of purified water is placed in a 20 L Baron box, into which the filtered actinomycete SIID11972 solution is added.

[0024] Next, 2 kg of the mixture was added to a 20 L Baron box. Specifically, 1000 g of soybean powder, 200 g of skim milk, 200 g of starch (potato starch), 400 g of trehalose, and 200 g of actinomycete SIID11972 solution were added and then cultured for 48 hours. Next, the mixture was transferred to a stainless steel tray, and the dried material was added and dried for 72 hours. Next, the dried mixture was dried until the moisture content was 8% or less. Finally, the dried mixture was mixed and sieved through a mesh.

[0025] When producing the triple culture, the powdered Lactobacillus fermentum, Lactobacillus subtilis, and actinomycete SIID11972 are mixed in a mass ratio of 2:1:1, which allows each bacterium to have a high purity and makes it easier to achieve the effect of the actinomycete SIID11972 remaining active without dormancy even in an oxygen-free environment such as the human intestine.

[0026] Lactobacillus fermentum may be NBRC 3071, a type of microorganism, or a metabolic derivative of NBRC 3071. NBRC 3071 may be in a liquid form, but is particularly preferably produced as a dried product. Specifically, 1.5% pure culture of NBRC 3071, 4% skim milk, 0.5% to 1.5% natural salt, 1% molasses, 0.5% monosodium glutamate, 2% to 6% potato starch, and 3% to 9% defatted soy flour are mixed with 100% purified water and stirred. After a predetermined growth period, the mixture is spray-dried using a spray dryer set at an inlet temperature of 150°C to 180°C and an outlet temperature of 75°C to 87°C, resulting in a viable cell count of 1.1 x 10 9 cfu / g ~ 1.2 × 10 10 It is produced as a dried powder with an average particle size of 1-9 μm and a cell density of 0.01 cfu / g. Metabolic derivatives of NBRC 3071 can be easily obtained by, for example, acclimatization in extreme environments, UV irradiation, chemical treatment, or genetic recombination.

[0027] In addition, tumor inhibitors can be formulated with cholera toxins and Lactobacillus fermentum culture as separate preparations or as one preparation.Hereinafter, the lactic acid bacteria culture that contains Lactobacillus fermentum as main component will simply be referred to as Lactobacillus fermentum.When each is formulated as separate preparations, the administration time of Lactobacillus fermentum culture can be arbitrarily set relative to the administration of cholera toxins.That is, the administration time of Lactobacillus fermentum culture or its derivatives can be before or after the administration of cholera toxins, or simultaneously with the administration of cholera toxins, but it is preferred to administer 1 hour before the administration of cholera toxins or simultaneously with the administration of cholera toxins.

[0028] When administering tumor inhibitors, cholera toxins are suitably administered in the range of 0.005-200 mg / kg, preferably 5-100 mg / kg. Furthermore, Lactobacillus fermentum cultures are suitably administered in the range of 10-2,000 mg / kg, preferably 100-1,000 mg / kg. The tumor inhibitors are formulated with a suitable carrier for formulation and prepared into various dosage forms. For example, they can be mixed with various excipients such as dextrin, starch, gum arabic, lactose, sucrose, and crystalline cellulose, disintegrants such as carboxymethylcellulose and methylcellulose, and lubricants such as stearates, talc, and anhydrous silicic acid, and formulated into tablets, granules, or capsules. Tumor inhibitors in these dosage forms can be taken orally, which, compared to parenteral administration such as injection, can prevent the tumor inhibitory effect from being exerted locally. Furthermore, oral administration is relatively easy and inexpensive to carry out.

[0029] [Embodiment 2] The tumor inhibitor according to embodiment 2 of the present disclosure may be composed of a different composition from the composition constituting the tumor inhibitor according to embodiment 1. For example, the lactic acid bacteria culture according to embodiment 2 may be composed of 1.5% Lactobacillus fermentum (hereinafter referred to as Lb-f) culture solution, 4% skim milk powder, 1.5% natural salt, 1% molasses, 0.5% sodium glutamate, 6% potato starch, 7% defatted soybean flour, and 100% (wt%) purified water. In embodiment 2, the culture was cultured at 40°C for 48 hours, and then slurried using a mixer. The Lb-f culture was then dried using a spray dryer at an inlet temperature of 150°C and an outlet temperature of 75°C to produce a dry powder. The powder thus obtained and a cholera toxin (hereinafter, cefotaxime sodium (CTX) is exemplified) powder were sieved and then mixed in a weight ratio of 1:1.8-28.8 to obtain a test powder (CTX+Lb-f formulation).

[0030] Except for the above points, the tumor inhibitor according to Embodiment 2 may have features in common with the tumor inhibitor according to Embodiment 1. For example, Lb-f constituting the lactic acid bacteria culture according to Embodiment 2 may be NBRC 3071 or a metabolic derivative of NBRC 3071, and the tumor inhibitor according to Embodiment 2 may be formulated as tablets, granules, or capsules.

[0031] In the following Examples 1 to 4, the results of tumor growth inhibition tests using the above-mentioned Lb-f dry powder, CTX powder, and test powders are shown as examples.

[0032] Example 1: Tumor Growth Inhibition Test Next, a tumor growth inhibition test using the Lb-f dry powder, CTX powder, and test powder described in Embodiment 2 above, conducted in Example 1, will be described. In Example 1, the Lb-f dry powder, CTX powder, and test powder were suspended in saline before use. The volume of the solution at the time of administration was adjusted to 0.1 mL per 10 g of mouse body weight, and then orally administered via a catheter. Animal experiments were conducted in accordance with the experimental animal handling regulations of the China National Institute for Medical and Biological Products, with ad libitum feeding and SPF breeding. Human colon cancer (HT-29) cells (2 × 10) were subcutaneously transplanted into the backs of Balb / c nude mice (female, 4 weeks old, 65 females, 4-5 weeks old, weighing 7-11 g). 6 cells / animal), and the volume of the transplanted tumor is 100 mm 3 After reaching this level (14 days after implantation), the body weights and tumor volumes were averaged and the animals were divided into 13 groups of 5 animals per group. The test groups and dosages are shown in Table 1 below. The administration was carried out every 2 days for a total of 9 times. The volume of the implanted tumor was measured on days 0 and 20 after the start of the administration test, and the relative tumor volume was calculated. The relative tumor volume was calculated from the ratio of the tumor volumes on days 0 and 20 after the start of the administration test (tumor volume on day 20 / tumor volume on day 0). The implanted tumors were measured for their major and minor axes using calipers once every 5 days, and the tumor volume was calculated using the standard formula (V=L×w 2 The tumor volume was measured using a 100% x 0.52 (V, L, W) curve. V, L, and W represent tumor volume, major axis, and minor axis, respectively. The transplanted tumor weight was determined 20 days after the start of the test by measuring the volume of the transplanted tumor, then removing the tumor and measuring its weight. The tumor inhibition rate was calculated as (l - mean tumor weight in each treatment group / mean tumor weight in the control group) x 100%.

[0033] As shown in Table 1, the combination of Lb-f and CTX demonstrated a significant tumor suppression effect compared with the administration of Lb-f alone. In particular, the combination of Lb-f and CTX (50 mg / kg + 180 mg / kg Lb-f) demonstrated an improvement in tumor suppression rate of 188% and 129%, respectively, compared with the tumor suppression rates observed when Lb-f and CTX were administered alone. These results demonstrate that the combination of Lb-f and CTX significantly improved tumor suppression in human colon cancer tumors and reduced the CTX dose required for tumor suppression. Note that p in Table 1 represents the probability of the observed effect if the null hypothesis were true.

[0034] Example 2: Side-effect suppression test Next, a description will be given of a side-effect suppression test by oral administration of Lb-f, which was carried out in Example 2. In Example 2, Balb / c nude mice (40 females, 4 weeks old, weighing 8-10 g) were used, and the volume of the transplanted tumor was 100 mm 3 After reaching this level (14 days after implantation), the body weights and tumor volumes were averaged and the mice were divided into 8 groups of 5 mice per group. The experimental groups and doses are shown in Tables 2 and 3. As in Example 1, oral administration was performed 9 times, every 2 days. Each mouse's body weight was measured on days 0 and 20 after the start of the administration study. Blood samples were then collected from the retroorbital venous plexus for blood testing (1.0 mL per mouse). The white blood cell count was measured using a hemocytometer, and serum was prepared according to standard methods. Serum LDH (lactate dehydrogenase), ALT (alanine aminotransferase), AST (aspartate aminotransferase), Cr (chromium), and BUN (urea nitrogen) were measured using an automated biochemical analyzer (Hitachi Corporation) and a Begiman CX7 biochemical analyzer (Begiman Corporation). Increased LDH and Cr are indicators of organ inflammation, and increased BUN is an indicator of impaired renal function. The weight change rate (%) was calculated as follows: [weight gain (g) in the test group / weight gain (g) in the control group × 100%]. Other test methods and statistical processing of the measured values ​​were the same as in Example 1.

[0035] As shown in Table 2, the control group (CTX alone) showed a significant reduction in weight loss compared to the other groups. On the other hand, the combined treatment groups (CTX + Lb-f) significantly improved the weight loss observed in the control group. This improvement tended to be dose-dependent. Furthermore, the Lb-f alone treatment groups maintained weight loss rates comparable to those of the control group. Furthermore, as shown in Tables 2 and 3, blood parameters indicating cell and organ damage and dysfunction were measured. The combined treatment with CTX and Lb-f and the treatment with Lb-f alone showed similar effects compared to the control and control groups (CTX alone). These results demonstrate that the combined treatment with CTX and Lb-f significantly alleviates the side effects of CTX alone, such as cytotoxicity, organ damage, and impaired immune function. Furthermore, oral administration of Lb-f alone is highly safe for the body.

[0036] [Example 3] <Tumor Growth Inhibition Test> Next, a tumor growth inhibition test carried out in Example 3 will be described. In Example 3, human gastric cancer cells (SGC-7901) were subcutaneously transplanted (3 × 10) into the backs of Balb / c nude mice (52 females, 4-5 weeks old, weighing 7-11 g). 6 cells / animal), and the transplanted tumor volume was 100 mm 3 After reaching the above weight limit (14 days after transplantation), the body weights and tumor volumes were averaged and the mice were divided into 13 groups of 4 mice per group. The test groups and doses are shown in Table 4 below. Other test methods and statistical processing of measured values ​​were the same as in Example 3.

[0037] As shown in Table 4, even when targeting tumors derived from human gastric cancer cells, the combined administration of CTX and Lb-f showed a better tumor-suppressing effect than the single administration of CTX or Lb-f, as in the test on tumors derived from colon cancer cells. These results clearly demonstrate that the combined administration of CTX and Lb-f also exerts an excellent tumor-suppressing effect on tumors derived from human gastric cancer cells, making it possible to reduce the CTX dosage required for tumor suppression.

[0038] [Example 4] <Side-effect suppression test> Next, a description will be given of the side-effect suppression test carried out in Example 4. In Example 4, human gastric cancer cells (SGC-7901) were subcutaneously transplanted (3 × 10 cells / mouse) into the backs of Balb / c nude mice (32 females, 4 weeks old, weighing 8-10 g). 3 After reaching this level (14 days after implantation), the body weights and tumor volumes were averaged and the mice were divided into 8 groups of 4 mice per group. The test groups and dosages are shown in Tables 5 and 6 below. As in Example 1, oral administration was performed every other day for a total of 9 times. The body weight of each mouse was measured on days 0 and 20 after the start of the administration test. Blood was then collected from the retroorbital venous plexus for blood testing (1.0 mL per mouse). Serum preparation, blood LDH, Cr, and BUN measurements, other test methods, and statistical analysis of measured values ​​were the same as in Example 1.

[0039] As shown in Tables 5 and 6, the combined administration of CTX and Lb-f showed an excellent effect of improving side effects, as in Example 2. These results also clearly show that the combined administration of CTX and Lb-f significantly alleviates side effects such as cytotoxicity, organ damage, and decreased immune function caused by the administration of CTX alone, under administration conditions that provide an effective tumor-suppressing effect. Similarly, it is clear that oral administration of Lb-f alone is highly safe for the living body.

[0040] As is clear from the tests shown in Examples 1-4 above, tumor inhibitors containing CTX and Lb-f as active ingredients exhibit excellent tumor-inhibiting effects while suppressing side effects such as cytotoxicity. That is, CTX is highly useful as a target-directed tumor inhibitor bound to a compound capable of reacting with a specific substance in tumor cells. Furthermore, while exhibiting pharmacological effects against various diseases, including muscular dystrophy and diabetes, it can also be used to treat these conditions without concern for toxicity. Furthermore, because of its high safety when ingested, the tumor inhibitor can be taken orally and fully exert its pharmacological effects in the body.

Claims

1. A tumor inhibitor characterized by containing cholera toxins and a lactic acid bacteria culture as active ingredients.

2. The tumor suppressor according to claim 1, characterized in that the lactic acid bacteria culture contains Lactobacillus fermentum, Lactobacillus subtilis, and Actinomycete SIID11972.

3. The tumor inhibitor according to claim 1, wherein the lactic acid bacteria culture is composed of Lactobacillus fermentum, skim milk powder, natural salt, molasses, sodium glutamate, potato starch, and defatted soybean flour.

4. The tumor inhibitor according to claim 3, characterized in that the lactic acid bacteria culture is cultured at 0°C for 48 hours, then slurried using a mixer, and then produced as a dry powder using a spray dryer at an inlet temperature of 150°C and an outlet temperature of 75°C.

5. The tumor suppressor according to any one of claims 2 to 4, wherein the Lactobacillus fermentum is NBRC 3071 or a metabolic derivative of said NBRC 3071.

6. The tumor inhibitor according to claim 1, which can be formulated into tablets, granules, or capsules by mixing with at least one of dextrin, starch, gum arabic, lactose, sucrose, crystalline cellulose, carboxymethylcellulose, methylcellulose, stearates, talc, and anhydrous silicic acid.

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