JP5435608B2 - Inhibitor of TGF-β production from type 3 helper T cells in mammals containing Ganoderma extract as an active ingredient - Google Patents

Description

The present invention relates to an inhibitor of TGF-β production from type 3 helper T cells in mammals containing ganoderma extract as an active ingredient.

  Ganoderma has long been used as a folk medicine and has been known to have effects such as tonicity, sedation, blood pressure lowering, cardiac intensification, and diuresis.

  However, at present, there are many unclear points about the effectiveness of Ganoderma pharmacology, including the chemical basis.

  As an example of a drug using the pharmacological action of Reishi extract, there is Patent Document 1 below.

Japanese Patent No. 3278209 Patent No. 3278209 is patented by paying attention to the pharmacological action of Ganoderma extract as a renal disorder ameliorating agent by an anticancer agent.

  Conventionally, steroids have been frequently used for skin diseases in mammals such as dogs, but there have been cases where essential pathological conditions or symptoms such as skin thickening have worsened.

  As a result of verifying the improvement effect of various medical conditions by administering various drugs and compositions to the pathological condition in which the skin is fibrotic and thickened and the functional disorder has occurred, It was found that there was an effect of improving the medical condition such as marked skin thickening, and the chemical basis could be clarified.

  In addition, Ganoderma extract has an excellent effect on dermatitis caused by allergies and atopy, and the scientific basis for it has been clarified.

Accordingly, the present invention is effective against hypertrophic dermatitis, and to provide a TGF-beta production inhibitor from type 3 helper T cells in a mammal comprising as an active ingredient the ganoderma water extract.

  Other objects and novel features of the present invention will be clarified in embodiments described later.

In order to achieve the above object, an inhibitor of TGF-β production from type 3 helper T cells in a mammal (excluding an embodiment applied to atopic dermatitis) comprising a reishi water extract of an embodiment of the present invention as an active ingredient. ) Is characterized in that it suppresses the production of TGF-β, which is a cytokine from type 3 helper T cells, and is effective for hypertrophic dermatitis caused by TGF-β.

  In the present invention, among the helper T cells involved in immunity of mammals, it has been found that Ganoderma extract has an action of suppressing biological reactions caused by Th2 and Th3.

According to the present invention, (inhibiting the production of TGF-beta is a cytokine from type 3 helper T cells) to suppress Th3 biological response by administration of Ganoderma water extract, hypertrophic dermatitis due to TGF-beta The medical condition of can be remarkably improved.

Hereinafter, as the best mode for carrying out the present invention, an embodiment when applied to the treatment of mammals with Ganoderma lucidum will be described with reference to the drawings.

  It was clarified that the cause of atopy and allergy in mammals is IgE antibody, and in 2003, the same cause of humans is the Th2 living body among helper T cells (Th1, Th2, Th3) involved in mammal immunity. It was suggested that this was a reaction. This cause is known as the hygiene hypothesis.

  Development and interpretation of a new test for atopy and allergy in dogs and cats suggests that the cause is an intrinsic Th2 biological reaction. In addition, the present inventor found out that the Th3 biological reaction is involved in the onset of atopy, and obtained the knowledge that it is also involved in the formation of a tumor.

  The present inventor has verified the effect of improving a disease state by administering various drugs and compositions for treatment of a disease state in which a mass in a dog or cat, for example, a skin fibrosis or thickening and a functional disorder has occurred. As a result, it has been found that the administration of Ganoderma extract has a remarkable effect of improving the medical condition.

  Conventionally, the chemical basis for the action of Ganoderma extract on Th3 biological reaction has not been shown, but the present inventor administered Ganoderma extract to dogs that developed hypertrophic dermatitis caused by Th3 biological reaction. The action was observed, and each helper T cell and its cytokines (Th1, Th2, Th3) were examined for phenotypic and endogenous biological responses before and after administration. It was proved that it was able to suppress effectively. The test results of the phenotypic biological reaction and the endogenous biological reaction are described in detail in Examples below.

  The ganoderma extract used here is dried from a well-ripened fruit body (mushroom) of ganoderma (not only natural but also artificially cultivated), cut into small pieces, extracted with a solvent such as hot water, and dried. It is a powder. However, at the time of administration, it is optional to make it liquid or tablet form.

  As the solvent, water, ethanol, propylene glycol, butanol or the like can be used, and the extraction may be performed at room temperature or heated.

  When the mammal is a dog, the dose of ganoderma extract per day (weight when dry powder) is preferably 10 mg or more per kg of body weight, and if it is less than 10 mg, there was almost no effect of improving the medical condition. In addition, even if it administered more than 30 mg per kg body weight, the improvement effect was comparable compared with the case of 30 mg. Therefore, it can be said that the dose of ganoderma extract per day (weight when dried powder) is preferably 10 mg or more and 30 mg or less per kg of body weight. It is considered necessary to administer Ganoderma essence daily for at least one week or more until the improvement effect of the disease state becomes clear.

  By administering an appropriate amount of Ganoderma essence, the Th3 biological reaction of mammals can be suppressed. Specifically, until both the phenotypic biological reaction and the endogenous biological reaction for Th3 are within the normal range of the animal or less It is possible to suppress.

  According to this Embodiment, Th3 biological reaction of a mammal can be suppressed, mass production can be suppressed, and hypertrophic dermatitis, lymphocytic plasma cell disease or fibrosis can be treated.

  Ganoderma extract also has an effect of suppressing the Th2 biological reaction, specifically speaking, it suppresses both the phenotypic biological reaction and the endogenous biological reaction for Th2 within the normal range of the animal or below. It is possible. This is also effective for the treatment of atopic dermatitis.

  Next, the treatment method of the mammal by the ganoderma extract of this invention is explained in full detail by a typical Example.

  Case: Medium dog A weighing 14 kg, male 5 years old, hypertrophic dermatitis with thickened atopic eyelids, and developing libidodermatitis in the eyelids and nasal bridge, respectively.

  FIG. 1 is a photograph of the face of dog A on January 18, 2007 before administration of Ganoderma lucidum. The right and left eyelids are hypertrophic dermatitis, and the symptoms on the right side are severe. In addition, atopic dermatitis is seen in the nasal bridge.

  Table 1 below shows the phenotypic and intrinsic biological reaction test results (evolutionary Th biological reaction test results) of dog A performed on January 19, 2007 before administration of Ganoderma lucidum.

The inspections in Table 1 and Table 2 described later are performed according to the following procedure. That is, for the pretreatment of cells, peripheral blood mononuclear cells separated by specific gravity centrifugation using Ficoll were divided into a non-stimulation group and a stimulation group, and the stimulation group was subjected to activation stimulation with PMA and Ionomycin, and then the cell membrane Permeabilization was performed, and IFN-γ, IL-4, and TGF-β were stained with fluorescent antibodies as Th1, Th2, and Th3 cytokines, respectively. Next, for the Th paradigm pattern, the appearance rate (%) of each Th cell was calculated for the obtained sample by flow cytometry, and the Th pattern of each case was analyzed. The one corresponding to the unstimulated group is a phenotypic biological reaction, and the one corresponding to the stimulating group is an intrinsic biological reaction.

  From the test results of Table 1, the ratio of Th1 cells in the endogenous biological reaction is low, and the dog A in this case is in a stressed state. In addition, since the ratio of Th3 cells in the endogenous biological reaction is increasing, it is considered that this causes the skin of the eyelid to become fibrotic and thickened, resulting in functional disorder (barrier disorder). This condition is evidence of chronicity and suggests refractory, including prognosis.

  Based on the above findings, it is clinically or therapeutically important that the endogenous Th3 vital response is elevated in this case, and refrain from administration of steroids (reason: the essential pathological condition further worsens), and Th3 It was determined that it was necessary to reduce the biological response.

  The present inventor attempted to administer Ganoderma extract. Administration was once a day, and the daily dose was 4 tablets containing 66 mg (weight when dried powder) equivalent of Ganoderma extract. That is, the dose per kg body weight of dog A was 66 × 4/14 = 18.9 mg. Administration started on January 20, 2007, and administration was continued daily.

Table 2 below shows the test results of the phenotypic biological reaction and the endogenous biological reaction of dog A on February 1, 2007 (after 13 administrations) during the administration.

In Table 2, the numerical value on the right is the inspection value on February 1, 2007, and the left is the inspection value in Table 1 (January 19, 2007) for reference. From Table 2, in the phenotypic biological reaction, Th2 is reduced from 5 to 0.24% (below the normal range), and Th3 is also decreased from 1.26 to 0.27% (below the normal range). In the endogenous biological reaction, Th2 is reduced from 6 to 0.23% (below the normal range), and Th3 is also decreased from 3.18 to 1.81% (in the normal range). From the test results shown in Table 2, administration of Ganoderma extract suppressed the Th3 vital reaction and the Th2 vital reaction, and the clinical symptoms observed at the first visit were markedly improved.

  Fig. 2 is a photograph of the face of dog A as of February 11, 2007, after administration of Ganoderma essence even after the examination in Table 2. The condition of the right and left eyelids and the condition of the nasal bridge are considerably improved. I understand.

  FIG. 3 is a facial photograph of dog A as of February 24, 2007, in which administration of Ganoderma lucidum was continued even after the examination in Table 2, and the pathology of the left and right eyelids and the pathology of the nasal bridge were even better. In particular, the left eyelid is almost completely cured.

  Although the embodiments and examples of the present invention have been described above, it is obvious to those skilled in the art that the present invention is not limited thereto and various modifications and changes can be made within the scope of the claims. Will.

In the Example of this invention, it is a facial skin thickening photograph figure of the dog A which shows the medical condition before a treatment (January 18, 2007). In an Example, it is a facial skin thickening photograph figure of the dog A which shows the improvement state after a treatment (February 11, 2007). In an Example, it is a facial skin thickening photograph figure of the dog A which shows the improvement state after further continuous treatment (February 24, 2007).

Claims (1)

Is a cytokine from type 3 helper T cells to suppress the production of TGF-beta, characterized in that it is effective in hypertrophic dermatitis due to TGF-beta, mammal an effective ingredient ganoderma water extract Inhibitors of TGF-β production from type 3 helper T cells in (except for the mode applied to atopic dermatitis).