JPH09301878A - Tumor growth suppressing agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an agent for suppressing the growth of tumor by using powder of Lactobacillus brevis as a component. SOLUTION: Powder of factobacillus brevis prepared by the concentration. and freeze-drying of a cultured liquid of Lactobacillus brevis is used as a component of the agent. The cell powder can be produced by dissolving yeast extract, glucose, potassium dihydrogen phosphate, sodium hydrogen phosphate, sodium chloride, sodium hydroxide and defatted soybean extract liquid in water under heating, adding precipitated calcium carbonate, adjusting the pH, sterilizing with high-pressure steam, adding a seed of Lactobacillus brevis to the obtained medium, culturing the seed cell, concentrating or centrifugally separating the produced cells and freeze-drying the separated cells. The cells are prepared in the form of a preparation containing about 10<8> to 10<9> cells/g and administered by oral administration. The tumor growth suppressing agent containing the cell powder has immunological function promoting action and tumor cell growth suppressing action and exhibits remarkable effect especially by the combined use with mitomycin.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a tumor growth inhibitor containing Lactobacillus brevis powder, and particularly a tumor growth inhibitor containing Lactobacillus brevis powder useful for treating tumors with mitomycin.

[0002]

2. Description of the Related Art Lactobacillus brevis is a kind of lactic acid bacterium found in the "pickled" pickles of Kyoto. In recent years, attention has been rapidly gathered as an immune function promoting agent that enhances interferon production and promotes immune function. For example, Japanese Patent Fair 7-
No. 55908 discloses an immune function-promoting agent containing Lactobacillus brevis powder.

In Japanese Patent Publication No. 55908/1995, administration of Lactobacillus brevis powder produces interferon α production, interferon γ production, NK activity, 2
It is stated that it will be useful for the treatment and prevention of infectious diseases and tumors because it enhances -5A activity and promotes immune function.

On the other hand, various factors such as TGFα, TGFβ, TGFγ, and MAS IGF-I are involved in the growth of tumor cells.
It is known that I, PDGF, etc. are involved, but a direct relationship has not been clarified with interferon, which originally has a virus growth-inhibitory effect, and interferon production decreased in cancer patients. It is speculated that increasing the function would improve the immune function, improve the pathophysiology and quality of life of patients, and would be useful for the treatment and prevention of tumors. Administration of Lactobacillus brevis powder is recommended. The effect on tumor cell growth has not yet been studied.

[0005]

SUMMARY OF THE INVENTION Therefore, it is an object of the present invention to find out a use as a tumor growth inhibitor by actually administering Lactobacillus brevis powder to verify its effect on the growth of tumor cells. .

[0006]

According to the present invention, the above object is to concentrate a culture solution of Lactobacillus brevis.
A tumor growth inhibitor comprising a Lactobacillus brevis bacillus powder, which is achieved by a tumor growth inhibitor containing lactobacillus brevis bacillus powder obtained by freeze-drying, and particularly shows a remarkable effect when combined with tumor treatment by mitomycin, Provided.

The tumor growth inhibitor of the present invention is characterized in that it contains Lactobacillus brevis bacterium powder. The Lactobacillus brevis bacterium powder can be produced, for example, as follows.

First, a medium having the following composition is prepared. Yeast extract 0.5% Glucose 1.5% Potassium dihydrogen phosphate 0.5% Sodium hydrogen phosphate 2.0% Sodium chloride 0.425% Sodium hydroxide 0.0375% Defatted soybean extract 8.75% Precipitation Calcium carbonate 0.1% (For defatted soybean extract, add defatted soybeans to an aqueous solution of about 0.25N hydrochloric acid, add pepsin and let stand at 37 ° C for 40-48 hours with occasional stirring to allow digestion. After the centrifugation, the supernatant is removed and used as a defatted soybean extract solution) is added to water to dissolve by heating, and the solution is adjusted to pH 6.8-7.0. Then, autoclave sterilization is performed at 121 ° C. for 15 minutes.

Next, Lactobacillus brevis (La)
ctobacillus brevis subsp.
Coagulans) inoculated into this medium,
18-4 while stirring at a speed of 100 rpm at 35 ° C
Incubate for 0 hour. After concentrating or centrifuging this solution,
Freeze-dried Lactobacillus brevis bacteria to about 2 x 1
0 ⁹ -5x10 ¹⁰ atoms / g including bacterial powder can be obtained.

The obtained bacterial powder has an appropriate number of bacteria, for example, 10
⁸ - 10 ⁹ cells / after the adjustment of the number of bacteria in such dispersing aid g about to become as potato starch, powders added excipients and the like,
Oral administration is preferably performed in the form of tablets, capsules, granules, liquids and the like. In the case of the tablet of the preferred embodiment, it is convenient to use, for example, a tablet containing about 5 × 10 ⁷ bacteria / tablet.

The inventors of the present invention noted that oral administration of the preparation containing this Lactobacillus brevis powder increased the interferon γ in the serum and promoted human immune function, and as a result, continued research. , Lactobacillus brevis powder not only promotes immune function but also clearly shows an antitumor effect and suppresses the growth of tumor cells. It was found that the tumor growth inhibitory effect far superior to that of
This is the invention of the present application.

[0012]

EXAMPLES The details of the present invention will be described below with reference to examples. The inoculum of Lactobacillus brevis was placed in the above-mentioned medium, and the mixture was stirred at 25-35 ° C. at a speed of 100 rpm for 30 hours, cultivated for 30 hours, centrifuged at about 10000 rpm, and lyophilized to give Lactobacillus brevis. A bacterial powder containing about 2 × 10 ⁹ −5 × ^{10 10} bacteria / g was obtained. The resulting bacterial powder is (1) Gram-positive bacilli,
(2) Dissolved in calcium carbonate in the medium, (3) Lactic acid is produced from glucose in the medium, (4) Nitrate reduction ability is negative, (5) Gelatin degradability is negative, (6) Casein degradability is It was negative and was in agreement with Lactobacillus brevis from the viewpoint of glycolysis.

Yoshida's sarcoma was subcutaneously injected into rats at 1 × 10 ⁶ cells.
An animal was transplanted with ls and the sarcoma size 4 days after the transplantation was almost the same. The tumor-bearing rats were divided into 4 groups each consisting of 5 animals, and a control group, a mitomycin alone administration group, a Lactobacillus brevis bacterium alone administration group, and a mitomycin + Lactobacillus brevis bacterium combination administration group were set. 10 mg of Lactobacillus brevis alone and in combination
/ Kg was orally administered for 8 days. 2.4 for mitomycin
mg / kg was intraperitoneally administered once 4 days after the start of the test. A 0.5% methylcellulose solution was orally administered to the control group for 8 days.

The length, width and height of the tumor were measured and the tumor volume was calculated by the following formula. Tumor volume (mm ³ ) = tumor length x width x height /
6 The test results are shown in FIG.

FIG. 1 shows that the tumors in the control group grew to 5,268 mm ^{3 on the} 9th day after transplantation. The tumor volume in the mitomycin alone administration group was reduced to 32% of that in the control group. On the other hand, in the Lactobacillus brevis alone administration group, the tumor volume was reduced to 49% of the control group, and further, in combination with mitomycin, the tumor volume was reduced to 24% of the control group, and the Lactobacillus brevis powder grew in the tumor. It was demonstrated that it is effective for inhibition, and that a very remarkable tumor growth inhibitory effect can be achieved by using oral administration of Lactobacillus brevis powder at the time of tumor treatment with mitomycin.

[Brief description of drawings]

[FIG. 1] is a drawing showing the relationship between the administration days (horizontal axis) and tumor volume (vertical axis) when various drugs are administered to Yoshida sarcoma-transplanted rats.

Claims (2)

[Claims] 1. A tumor growth inhibitor comprising a Lactobacillus brevis bacterium powder obtained by concentrating and freeze-drying a culture solution of Lactobacillus brevis bacterium. 2. The tumor growth inhibitor according to claim 1, which is useful for tumor treatment with mitomycin.