JPH05132425A - Agent for preventing and treating autoimmune disease - Google Patents

Abstract

PURPOSE:To obtain an agent for preventing and treating autoimmune diseases, enabling extremely easy administration and capable of being continuously administered to a wide variety of patients and persons to necessitate the prevention of the disease without causing the side effect by using bacterial cell of lactic bacteria belonging to genus Lactobacillus as an active component. CONSTITUTION:A lactobacillus strain of genus Lactobacillus [e.g. Lactobacillus casei YIT9018 (FERM P-665)] is cultured in a medium and the bacterial cells are separated from the culture liquid by centrifugal separation, washed with distilled water and dried by heating at 100 deg.C to obtain bacterial cell powder. It can be used as it is as a preventive and treating agent for autoimmune diseases, however, the objective preventing and treating agent for autoimmune diseases, enabling extremely easy administration and capable of being continuously administered to a wide variety of patients and persons to necessitate the prevention of the disease without causing the side effect can be prepared by adding a preservability-improving assistant and other agents and forming the mixture in the form of a pharmaceutical preparation.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a drug for preventing or treating a group of diseases collectively called autoimmune diseases.

[0002]

BACKGROUND OF THE INVENTION Many diseases, which are collectively referred to as autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis, do not have simple causes, and have abnormal genetic factors, hormone endocrine environment, and immune function. It is thought to be due to the complex interaction of multiple factors such as virus infection. There is still no drug that is truly effective in treating this autoimmune disease, and most conventional treatments are symptomatic treatments that only suppress inflammation. For example, in the case of SLE, which is considered to be a prototype of systemic autoimmune disease in which lesions progress to various organs in the body and various types of autoantibodies are detected, the drug treatment is an adrenal steroid hormone drug (eg, dexamethasone). And anti-inflammatory treatment with immunosuppressants (eg, azathioproline, cyclophosphamide, mizoribine, cyclosporin A) and the like. However, these drugs have strong side effects and their use is associated with great risk.

Animal models of autoimmune diseases, including MRL / lpr mice, have contributed greatly to the progress of research on autoimmunity and provided accurate information that could not be obtained in studies on human autoimmune diseases. However, the cause of autoimmune diseases remains unclear, and therefore, no remarkable progress has been made in research on effective prophylactic / therapeutic agents.

[0004]

On the other hand, in recent years, it was confirmed that Lactobacillus has an action of enhancing the human non-specific immune surveillance mechanism [Yokokura, Pharmacology and Therapeutics, vol.17 (6), 1875].
■ 1897 (1989)]. An object of the present invention is to focus on the action of lactic acid bacteria as described above, and to provide a preventive / therapeutic agent for autoimmune diseases using the same.

[0005]

The preventive / therapeutic agent for autoimmune diseases according to the present invention contains a lactic acid bacterium of the genus Lactobacillus as an active ingredient. The lactic acid bacterium belonging to the genus Lactobacillus used for the preventive / therapeutic agent for the autoimmune disease of the present invention,
Any lactic acid bacterium belonging to Lactobacillus may be used, such as Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus helveticus, Lactobacillus eugleti. The cells may be any of freeze-dried live cells, heat-dried dead cells, and the like. The lactic acid bacterium as a raw material is prepared by culturing in an arbitrary synthetic medium according to a conventional method for lactic acid bacterium culture, collecting the cells, and freeze-drying or heat-drying. The lactic acid bacterium does not have to be a viable cell, and may be a dead cell or a crushed cell.

[0006] Dried cells are used as they are to prevent autoimmune diseases.
It can be used as a therapeutic agent, but if necessary, it may be formulated by adding an auxiliary agent for improving storage stability and other agents. No special conditions are required for storage after formulation. The preventive / therapeutic agent for autoimmune diseases according to the present invention comprises
It is administered to a patient or a person in need of prevention by oral administration, intravenous administration or direct administration to the affected area. In the case of oral administration, an appropriate dose is about 0.1 g to 5 g on consecutive days or every other day. 5 mg for intravenous administration
Approximately 500 mg is suspended in physiological saline or the like for administration. Lactobacillus Lactobacillus is a non-pathogenic bacterium that is resident in the intestines of humans and many other animals, and has been used in food production for a long time, so the safety of oral administration has been confirmed. ing.

[0007]

【Example】

Example 1 Lactobacillus casei YIT9018 (Microtechnical Research Institute No. 665) was cultured in Rogosa's medium, the cells were centrifuged from the culture solution, and the obtained cells were washed with distilled water and then at 100 ° C. It was dried by heating with to obtain a bacterial cell powder. In the following test examples, the preventive / therapeutic action of autoimmune diseases was investigated for the drug consisting only of the bacterial cell powder.

Test Example 1 40 MRL / lpr mice (4-week-old female), an autoimmune disease model animal, were prepared, and 20 of them were fed with the drug of Example 1 and the remaining 20 (control group). ) Were fed with basic feeds respectively. The basic feed is MM-3 for breeding mice, rats and hamsters.
When using the feed (Funabashi farm product; composition below), the addition rate when the drug of Example 1 was added was 0.05% by weight.

Basic feed composition: Ash (wt%) 6.7 Lipid (wt%) 5.5 Protein (wt%) 20.7 Moisture (wt%) 3.6 Carbohydrate (wt%) 63.5 Total energy ( kcal / 100g) 417 Metabolic energy (kcal / 100g) 386 The results are shown in FIG. 1. The 50% survival rate of the drug administration group was 48 weeks old, while that of the control group was 36%. Was a week old.

Test Example 2 In order to investigate the cause of prolongation of the life of the drug administration group in Test Example 1, 20 same autoimmune disease model animals MRL / lpr mice as those used in Test Example 1 were prepared.
The animals were fed with the drug-added feed, and the 10 animals were fed with the basal feed, respectively. And 12 weeks old and 22
Five mice in each group were sacrificed at the age of week, and the blood anti-DNA antibody titer and the B220-positive T cell ratio in spleen mononuclear cells were measured. The former was analyzed by the ELISA method, and the latter was analyzed by an Epix Elite Analyzer (Coulter) using a fluorescent labeled antibody.

As a result, the increase in blood IgG class anti-DNA antibody titer, which is one of the causes of the development of nephritis, was suppressed in the drug administration group (FIG. 2). In addition, the proportion of abnormal cells infiltrating the immune system with the progress of autoimmune disease, that is, the ratio of B220-positive T cells was also decreased by drug administration (Fig. 3).

[0012]

As described above, the lactic acid bacteria of the genus Lactobacillus can prevent and treat autoimmune diseases.
By using Lactobacillus lactobacillus, which is safe in terms of safety, as the main component, the preventive / therapeutic agent for autoimmune diseases of the present invention is extremely easy to administer, and can be used for a wide range of patients and prevention without fear of side effects. It is also excellent in that it can be taken daily by those who need it.

[Brief description of drawings]

FIG. 1 is a graph showing test results in Test Example 1.

FIG. 2 is a graph showing test results in Test Example 2.

FIG. 3 is a graph showing test results in Test Example 2.

 ─────────────────────────────────────────────────── ─── Continued Front Page (72) Inventor Mariko Kawaguchi 1-1-19 Higashishimbashi, Minato-ku, Tokyo Yakult Honsha Co., Ltd. (72) Inventor Makoto Owaki 1-1-19 Higashishimbashi, Minato-ku, Tokyo Stocks Company Yakult Head Office

Claims (1)

[Claims] 1. A method for preventing autoimmune diseases, which comprises a lactic acid bacterium belonging to the genus Lactobacillus as an active ingredient.
Therapeutic agent.