KR101354961B1 - Fermented Job's tears extract for the prevention and treatment of rheumatoid arthritis and a method for preparation thereof - Google Patents

Abstract

The present invention relates to a fermented yeast extract for the prevention and treatment of Rheumatoid arthritis and a method for producing the same, more specifically, the fermentation bacteria, yeast, yeast, or yeast and yeast, characterized in that the prevention of rheumatoid arthritis and The present invention relates to a therapeutic fermented barley-containing extract and a method for preparing the same, and furthermore, to a health functional food composition containing the fermented barley-containing extract.

Description

Fermented Job's tears extract for the prevention and treatment of rheumatoid arthritis and a method for preparation

The present invention relates to a fermented yeast extract and a method for producing the same for the prevention and treatment of rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune disease that causes inflammation by attacking one's joints or parts of the body due to an abnormal immune system, and indicates pain and swelling of various joints such as fingers, hands, feet, wrists, ankles and knees. It is a systemic chronic inflammatory disease that can cause abnormalities in many other organs such as skin, lungs and eyes.

Since the direct cause of such arthritis is not clear yet, research on it is ongoing. As of now, no effective treatment or prevention method for arthritis such as rheumatoid arthritis has been well known. There are many things to do.

Although various treatments and treatments for arthritis have been proposed, these treatments and treatments are difficult to be regarded as the fundamental treatments. Hormones such as steroid hormones have been known and used as treatments for arthritis, but side effects have been reported. As it became more difficult to use.

Arthritis, especially chronic rheumatoid arthritis, causes severe pain in patients, so must take anti-inflammatory drugs, etc. Aspirin has been widely used for a long time to alleviate such pain. However, since aspirin has a fatal effect on the stomach of the person, it is considered difficult to continuously take the amount necessary to treat arthritis.

Conventional chemotherapy agents have drawbacks such as side effects that hinder the long-term use of the drugs, lack of anti-inflammatory effects and lack of efficacy against arthritis that has already occurred. There is a constant demand, and most arthritis treatments in use today have some side effects, although there are some differences and personal differences, and especially for the treatment of rheumatoid arthritis, you need to take medication for a long time, Developing medicines with fewer side effects is a very important and urgent problem.

Yulmu is a monocotyledonous plant and is an annual herb that belongs to the rice plant family. Yulmu, which is called cheonggok, barley scallop, sugar, etc., has a high content of saturated fatty acids, and its components include phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol and lysophosphatidyl choline. choline) and the starch composition has been reported to have a high content of amylopectin (Amylopectin).

Yulmu's general efficacy is known to improve diuretic and sedative effects, such as lipid metabolism improvement.

KR 10-0811066 B1 (2008.03.06.Notification) KR 10-0656571 B1 (announced Dec. 13, 2006) KR 10-2008-0091743 A (announced October 14, 2008)

An object of the present invention is to provide a fermented yeast extract and a method for producing the same for the prevention and treatment of rheumatoid arthritis.

The present invention provides a fermented yeast extract and a method for producing the same for the prevention and treatment of rheumatoid arthritis.

More specifically, in accordance with an aspect of the present invention, the fermentation bacteria provides yeast, yeast, or yeast and yeast-containing extract for the prevention and treatment of rheumatoid arthritis.

According to another aspect of the present invention, the yeast is an alcoholic fermentation yeast, characterized in that it provides a fermentation rate containing extract for the prevention and treatment of rheumatoid arthritis.

According to another aspect of the invention, rheumatoid arthritis, characterized in that the alcohol content is preferably 8 to 20% by weight, or more preferably 12 to 16% by weight based on the total weight of the extract It provides an extract containing fermentation rate of radish for the prophylaxis and treatment of.

According to another aspect of the present invention, the fermentation rate-containing extract provides a fermentation rate-containing extract for the prevention and treatment of rheumatoid arthritis, characterized in that it has the effect of inhibiting the expression of chondrase, inflammation-inducing factor and rheumatoid factor. .

According to another aspect of the present invention, it characterized in that it contains the extract containing the fermentation rate of radish, provides a health functional food composition for the prevention and treatment of rheumatoid arthritis.

According to another aspect of the present invention, as a method of producing the fermented yulmu extract,

Increasing the yield;

Fermenting by adding koji, yeast, or koji and yeast to the cooked yulmu; And

Concentrating the fermented barley

It characterized by comprising, it provides a method for producing a fermentation rate containing extract for the prevention and treatment of rheumatoid arthritis.

According to another aspect of the present invention, in the above production method, the fermentation step is characterized in that the fermentation by adding 5 to 18 parts by weight of yeast and 0.5 to 5 parts by weight of yeast with respect to 100 parts by weight of the steamed yuljin To provide a method for producing a fermented yeast containing extract for the prevention and treatment of rheumatoid arthritis.

According to another aspect of the present invention, in the above production method, the yeast is an alcohol fermentation yeast, it provides a method for producing a fermentation rate containing extract for the prevention and treatment of rheumatoid arthritis.

The yeast is not particularly limited in its kind, and may be used strains known in the art or similar fields, more preferably alcohol fermentation yeast may be used.

The alcohol fermentation yeast is not particularly limited in its kind, and may be used strains known in the art or similar fields, more preferably Saccharomyces cerevisiae ( Saccharomyces cerevisiae ) can be used.

Saccharomyces cerevisiae strain used in the present invention was used to purchase the "Songcheon Yeast Development Research Institute" products that are sold for general alcohol fermentation.

Bio Nuruk used in the present invention was used by purchasing the "Korea Enzyme Co., Ltd." product.

The yulmu is a perennial herb belonging to the monocotyledonous rice plant family, and the yulmu refers to its leaves, stems, roots or seeds.

The fermentation refers to a phenomenon in which organic matter is decomposed and changed by the action of microorganisms, and in a narrow sense, it refers to a phenomenon in which organic matter is anaerobicly decomposed by microorganisms, and in a broad sense, useful substances are produced by microorganisms. Say that. Due to the decomposition or synthesis of organic matter by the action of such microorganisms, the raw ingredients of the original food complex changes and a unique flavor is added to the food is called fermented food. Examples include miso, soy sauce, kimchi, bread, alcohol, cheese, yogurt, and salted fish.

In the present invention, by using the fermented barley, not the general barley, it is possible to obtain the effect of destroying the toxic substances in the barley, etc. through the fermentation process, furthermore the productivity, digestive power and body absorption of the bioactive material is more enhanced The effect can be obtained. In addition, fermented yeast contains more abundant protein, essential amino acids, essential fatty acids and vitamins than non-fermented yeast, and thus it is highly desirable to provide extracts and compositions for the prevention and treatment of rheumatoid arthritis.

The method of fermenting the yulmu is not particularly limited, and may be performed by a method known in the art or a similar field.

The method of extracting the fermentation rate of radish is not particularly limited, and may be performed by a method known in the art or a similar field.

The method of preparing the fermented yeast extract is not particularly limited and may be performed by a method known in the art or a similar field.

Increasing the yield;

Fermenting by adding koji, yeast, or koji and yeast to the cooked yulmu; And

Concentrating the fermented barley

Characterized in that, the method for producing a fermentation rate containing extract for the prevention and treatment of rheumatoid arthritis is not particularly limited in the method of performing the specific step, can be carried out by a method known in the art or similar fields have.

In the fermentation step, more preferably, the fermentation may be performed by adding 5 to 18 parts by weight of Nuruk and 0.5 to 5 parts by weight of yeast, with respect to 100 parts by weight of the cooked steam. The fermentation may be performed by adding 8 to 12 parts by weight of yeast and 0.5 to 3 parts by weight of yeast.

In addition, in the fermentation step, the yeast is not particularly limited, more preferably alcoholic fermentation yeast can be used, most preferably Saccharomyces cerevisiae can be used.

Fermented yeast extract of the present invention has a prophylactic and therapeutic effect of rheumatoid arthritis. In more detail, the fermented lychee extract of the present invention inhibits the expression or activity of chondrase, has an excellent antioxidant activity, inhibits the expression of inflammatory factors, and has an excellent anti-inflammatory effect such as increasing the production of anti-inflammatory factors. It has the advantage of providing extracts and nutraceutical compositions excellent in the prevention and therapeutic efficacy of rheumatoid arthritis, such as reducing rheumatoid factor.

Figure 1 relates to the amount of NO produced in each sample group, a graph showing that NO production is reduced by the fermentation rate radish extract.
Figure 2 relates to the amount of PGE ₂ production of each sample group, a graph showing that the PGE ₂ production is inhibited by the fermentation rate of radish extract.
Figure 3 relates to the expression level of IL-1β of each sample group, a graph showing that the expression of IL-1β is reduced by the fermentation yulmu extract.
4 is a graph showing the expression levels of MMP-1 and -3 in each sample group, showing that the expression of MMP-1 and -3 is reduced by the fermentation rate extract.
5 is related to the incidence of arthritis in each sample group, a graph showing that the incidence of arthritis is reduced by the fermentation rate of radish extract.
Figure 6 relates to the clinical score of arthritis severity of each sample group, a graph showing that the arthritis severity score is lowered by the fermentation rate of radish extract.
Figure 7 relates to the foot edema of each sample group, a graph showing that the degree of edema is improved by the fermented yeast extract.
Figure 8 relates to the expression level of IL-1β of each sample group, a graph showing that the expression of IL-1β is reduced by the fermentation yulmu extract.
Figure 9 relates to the expression level of RF in each sample group, a graph showing that the expression of RF is reduced by the fermented dew extract.
10 is a diagram showing the histopathological observation results of each sample group in which rheumatoid arthritis is induced.
11 is a graph showing histopathological scores of each sample group induced by rheumatoid arthritis.

Hereinafter, the present invention will be described in more detail by describing Examples and Experimental Examples. However, the following Examples and Experimental Examples are only examples of the present invention, and the contents of the present invention should not be construed as being limited thereto.

Example  One

Preparation of Fermented Yulmu Extract

After immersing 100 g of commercial yulmu and 100 g of rice, the mixture was steamed at 120 ° C. for 15 minutes. The cooked yulmu and rice were ground with a grinder and mixed. Here the addition of 150g of water, and the bio-yeast based on the total weight of the mixture (Korea Enzyme Co., Ltd.) of 3 weight% and the alcohol fermentation yeast Saccharomyces on MRS three Levy cyano (Saccharomyces cerevisiae ) (produced by Songcheon Yeast Development Research Institute) was added and fermented at 25 ° C. for 7 days. After the above process to prepare a fermentation rate of alcohol content of about 14% (wt% measured based on the total weight of the fermentation rate of the extract prepared by the above process) to separate the sake lees and filtered, rotary vacuum concentrator ( Eyela, Tokyo Rikakikai Co., Tokyo, Japan), followed by a freeze-drying process to obtain the fermented yeast extract of the present invention.

Experimental Example 1

Anti-inflammatory Activity of Fermented Yulmu Extract: Determination of NO Production

NO (nitrogen monoxide) is an antioxidant and an anti-inflammatory agent, which is known to be an indicator that can diagnose the degree of arthritis by increasing the amount of production when arthritis, especially rheumatoid arthritis occurs in the body. In order to measure the anti-inflammatory activity of the fermented Yulmu extract, an experiment was performed to measure the amount of NO production using the cells cultured as follows. NO production measurement was performed according to the Greries Reagent System method.

(1) Cell culture

Murine macrophage cell line RAW 264.7 cells were obtained from Korean Cell Line Bank (KLCB), and 5% CO using Dulbecco's Modified Eagle's Medium (DMEM) low glucose medium supplemented with 10% Fetal Bovine Serum (FBS) and 1% antibiotics. at 37 ℃ incubator for ₂ it is present once per 2 to 3 days were the sub-cultured.

(2) NO production reduction

RAW 264.7 cell lines were dispensed into 96 well plates at 1 × 10 ⁵ cells / well to prepare 7 samples and incubated for 24 hours. Then, six of these samples were treated with 100 ng / mL of lipopolysaccharide (LPS), a bacterial proinflammatory agent, respectively, to induce inflammation, and then the fermented yeast extract prepared in Example 1 on these six samples. Were treated at different concentrations (0, 62.5, 125, 250, 500, 1000 μg / mL, respectively) and incubated for 24 hours. After 24 hours, 100 μL of the cell culture supernatant was taken into a 96-well plate, and the same amount of grease reagent was added thereto and reacted for 10 minutes, and then the absorbance was measured at 540 nm using a microplate reader. NO production is nitrite (Nitrite, NO ₂ ^-) present in the cell culture was conducted in the form of measuring the amount, as compared with the standard line is obtained by using sodium nitrite (Sodium nitrite, NaNO ₂₎ nitrite concentration in the (μM) Was calculated.

As a result, it was confirmed that the amount of NO produced in the cell culture after LPS treatment was increased by about three times compared to the control without LPS treatment. Thus, the fermented yeast extract (FYM) prepared in Example 1 was obtained. When treated, NO production was found to show a significant decrease, especially when treated at a concentration of about 1000μg / mL it was confirmed that the NO production is reduced to a level similar to the control group not treated with LPS (Fig. One).

Experimental Example 2

Anti-inflammatory Activity of Fermented Yulmu Extract: PGE ₂  And IL Production of -1β

Prostaglandin E2 (hereinafter referred to as PGE ₂ ) is known to be a factor that worsens inflammation of soft tissues, and interleukin-1β (IL-1β) is known as a cytokine to promote inflammation. In order to measure the decrease of the production amount of PGE ₂ and IL-1β by the fermented yeast extract, cells cultured as in Experimental Example 1 were tested using an enzyme immunoassay kit.

RAW 264.7 cell lines were dispensed into 96 well plates at 1 × 10 ⁵ cells / well to prepare 7 samples and incubated for 24 hours. Then, six of these samples were treated with LPS 100ng / mL, respectively, to induce inflammation, and then, each of these six samples had different concentrations of fermented yeast extract prepared in Example 1 (0, 62.5, 125, 250, 500, 1000 μg / mL) and then incubated for 24 hours. After 24 hours, 100 μL of the cell culture supernatant was taken in a 96 well plate to determine the content of PGE ₂ and IL-1β.

As a result, it was confirmed that the amount of PGE ₂ produced in the cell culture after LPS treatment was increased by about 15 times or more compared to the control without LPS treatment, and thus, the fermented yeast extract (FYM) prepared according to Example 1 was obtained. In the case of treatment, PGE ₂ production was shown to show a significant decrease (FIG. 2).

In addition, as a result of the experiment for IL-1β, it was confirmed that the amount of IL-1β produced in the cell culture after LPS treatment was increased by about three times compared to the control without LPS treatment, according to Example 1 When the fermented yeast extract (FYM) was prepared, IL-1β production was shown to show a significant decrease (FIG. 3).

Experimental Example  3

Cartilage Protection Effect of Fermented Yulmu Extract: Determination of MMPs Expression

Matrix metalloproteinases (MMPs) are known to induce the destruction of extracellular matrix (ECM) of cartilage and joints, and to progressively worsen diseases such as arthritis. Experiments were performed using cells cultured as follows to determine whether the fermented yeast extract reduced MMPs expression.

(1) Cell culture

SW1353 cell line (human chondrosarcoma cell line) from American Type Culture Collection (ATC) was distributed and 10% FBS and 1% antibiotics (penicillin / streptotome) in DMEM high glucose in 5% CO ₂ incubator at 37 ° C. Passage was cultured 2-3 times a week in the medium to which mycin) was added.

(2) Treatment of TNF-α and Fermented Yulmu Extract in Cell Cultures

① Preparation of sample group to measure the extent of MMPs expression reduction

SW1353 cells were dispensed into 96 well plates at a concentration of 1 × 10 ⁵ cells / mL using DMEM high glucose medium to prepare 7 samples, and 6 of them were tumor necrosis factor-α. And 50ng / mL of TNF-α), and fermented yeast extract (FYM) prepared according to Example 1 in each of these six samples at different concentrations (0, 62.5, 125, 250, 500 and 1000 μg / mL) and then incubated for 24 hours. After 24 hours, the cell culture supernatant was taken and the production of MMP-1 and -3 was measured by ELISA (Enzyme-linked immunosorbent assay) method.

TNF-α is known as a substance that reflects the occurrence of inflammation, such as by inducing the activity of vascular endothelial cells to promote the secretion of various chemicals, thereby promoting the migration of inflammation-related cells.

As a result, it was confirmed that the production amount of MMP-1 and -3 in the cell culture after treatment with TNF-α was significantly increased compared to the control group not treated with TNF-α, thus prepared by Example 1 When the fermented Yulmu extract (FYM) was treated, it was confirmed that the production of MMP-1 and -3 significantly decreased (FIG. 4).

Experimental Example 4

Validation of Rheumatoid Arthritis Improvement Effect of Fermented Yulmu Extract Using Animal Model

(1) animal model and experiment design

40 males of 6 weeks old (Orient, Korea) of DBA / 1J mice were obtained, purified in experimental animal breeding room for 1 week, and the experiment was started at 7 weeks of age.

The experimental animals were divided into four groups, each of 10 animals, after weighing. The first group was a normal control group without any treatment (Normal), the second group was a collagen-induced arthritis (collagen-induced arthritis) and then treated with no treatment (CIA), the two groups were normal Solid feed was given. The third group is a positive control (Celecoxib) fed a feed containing 0.03% of the anti-inflammatory drug Celecoxib (product of Pfizer Pharmaceuticals Co., Ltd.) after inducing CIA, and the fourth group was prepared by Example 1 after CIA induction. A feed group containing 0.3% of the fermented yeast extract was composed of a fed test group (FYM). To confirm the efficacy of the fermented Yulmu extract, an autopsy was performed 5 weeks after feeding.

In order to induce the collagen-induced arthritis, bovine type II collagen (Bovine type II collagen, Chondrex, USA) isolated and quantified according to a known method, an equivalent amount of complete Freund's adjuvant (Sigma, USA) and an electric homogenizer ( Using an electirc homogenizer) was evenly mixed to maintain an emulsion to make an emulsion. 50uL was injected intradermally 2 ~ 3cm away from the base of the mouse tail, and additionally inoculated 3 weeks after the first injection. For inoculation, incomplete Freund's adjuvant (Sigma, USA) was used.

(2) Visual evaluation method of the development of rheumatoid arthritis

After inducing rheumatoid arthritis according to the above method, the occurrence and severity of arthritis were examined at each time by observing the occurrence of redness, swelling, and malformation of the foot of the animal model three times a week. The severity of arthritis was performed by general visual examination. Scoring was carried out according to the existing method, the criteria are shown in Table 1 below.

score The progress of the disease 0 Erythema and swelling do not appear One Erythema and slight swelling only in the middle of the foot or ankle joint 2 Erythema and slight swelling from the ankle joint to the middle of the foot 3 Elongated erythema and moderate swelling from the ankle joint to the metatarsal joint 4 Erythema and severe swelling, including ankle, foot and toe

(3) Visual evaluation result of the development of rheumatoid arthritis

About 30 days after the first injection of collagen, redness and edema began to be observed, and the onset of arthritis was the fastest in the negative control group (CIA) and showed an incidence of 100%. The incidence was the slowest in the positive control (Celecoxib), and the incidence was about 60% at the end of the experiment. The test group (FYM) treated with the fermented yeast extract prepared in Example 1 was slower than the negative control (CIA), and finally showed an incidence of 90% (FIG. 5).

The negative control group (CIA) had a rapid onset of arthritis and a high arthritis score of nearly 60. On the other hand, the positive control group (Celecoxib) showed a markedly low arthritis score of about 20 points. In the test group (FYM), 41 points were significantly lower than the negative control arthritis score (Fig. 6).

(4) measurement result of edema degree

Before the end of the experiment, the thickness of the foot increased due to edema was measured using a Digimatic thickness gage (Mitutoyo, Japan) to determine the average thickness of the four feet.

When rheumatoid arthritis develops, the synoviium in the joints becomes inflamed and white blood cells in the blood gather into the joints, resulting in increased joint fluid and swelling in the joints. In this experiment, edema began to appear in the CIA-induced sample group about 30 days after the first injection of type 2 collagen. At the end of the experiment, edema was observed in most sample groups except the normal control group (Normal). The highest edema was observed in the negative control group (CIA), and the edema was significantly reduced in the positive control group (Celecoxib). The test group (FYM) treated with the fermented yeast extract prepared in Example 1 also showed a significant decrease in edema compared to the negative control (CIA), and the fermented yeast extract of this test substance effectively prevented edema caused by arthritis. It was judged to improve (FIG. 7).

(5) decreased expression of IL-1β

The designed experiment was terminated at 8 weeks and blood was collected from posterior vena cava of each group to separate serum. Samples were stored at -70 ° C until measurement, and thawed immediately before the experiment, and the expression level of IL-1β was measured using the mouse ELISA kit (R & D system, USA) according to the manufacturer's instructions.

As a result, IL-1β showed the highest expression in the negative control group (CIA), and the expression level of IL-1β in the positive control group (Celecoxib) was significantly reduced compared to the negative control group (CIA). (FYM) showed a tendency to decrease than the negative control (CIA) (Fig. 8).

(6) decreased expression of Rheumatoid factor (RF)

The designed experiment was terminated at 8 weeks and blood was collected from posterior vena cava of each group to separate serum. The samples were stored at -70 ° C until the measurement, and thawed immediately before the experiment, immunoglobulin G (hereinafter referred to as IgG) and IgM were measured using ELISA kit (SHIBAYAGI, Japan) according to the manufacturer's instructions.

Rheumatoid factor is an autoantibody that binds to the Fc (Fragment, crystallizable) region of IgG and is known as an important factor in the diagnosis and prognosis of rheumatoid arthritis. In general, IgM rheumatoid factor or IgG rheumatoid factor is the measurement target, of which the diagnostic value of IgM rheumatoid factor is the highest.

Experimental results showed that IgM and IgG were the highest in the negative control (CIA). On the other hand, the positive control group (Celecoxib) and the test group (FYM) were observed to be significantly reduced compared to the negative control group (CIA). IgG was also significantly decreased in the positive control group (Celecoxib) and test group (FYM) compared to the negative control group (CIA) (FIG. 9).

(7) histopathological observation

After the designed experiment, four groups of each group were taken and fixed in 10% neutral formalin solution for 2 days, and then immersed in 10% EDTA solution again for 2 weeks. Was demineralized. After embedding in paraffin through a general tissue treatment process, a tissue section of 4㎛ was prepared. H & E staining was performed on the tissue sections to observe tissue changes, and the degree of loss of proteoglycan in the knee cartilage was examined by light microscopy through TB staining. When observing histopathological changes in the joints, the criteria for evaluation of the lesions were followed by Platter-Zyberk et al., Which are shown in Table 2 below. The final score was expressed as the average of each group by adding the following two scores.

score Erosion score scale 0 No destruction of cartilage or bone 1-2 Local cartilage erosion 3 Erosion 4 Overall cartilage erosion and bone erosion score Synovitis 0 No inflammation 1-2 Infiltrating cells in the membrane layer and / or inner membrane layer become somewhat enlarged 3 Hypertrophy of the membrane layer and / or more pronounced influx of membrane lining cells 4 Cells appear in the synovial space
Observation of synovial hypertrophy and synovial severe infiltration in many inflammatory cells

As a result, the normal control group showed normal joint structure and abundant proteoglycan content in cartilage, whereas the negative control group (CIA) showed distinct articular cartilage loss and bone erosion, and the surrounding area due to excessive infiltration of inflammatory cells in the joint capsule Excessive growth of tissue was observed. In the positive control (Celecoxib), weak joint cartilage loss and inflammatory cell infiltration were observed. In test group (FYM), infiltration of inflammatory cells, loss of proteoglycan in articular cartilage, and growth of surrounding tissue were moderately observed in both anterior and posterior ankles, and overall arthritis index was significant compared to negative control (CIA). Low observed (FIG. 10, FIG. 11).

Therefore, the histopathological observations of the ankle and ankle showed that the negative control group (CIA) had the highest arthritis index, while the positive control group (Celecoxib) and the test group (FYM) had significantly decreased arthritis index compared to the negative control group (CIA). It was.

Claims (11)

delete delete delete delete delete delete Increasing the yield;
Fermenting by adding Bio Nuruk and Saccharomyces cerevisiae to the cooked yulmu; And
As a method for producing a fermented yulmu containing extract for the prevention and treatment of rheumatoid arthritis, characterized in that it comprises the step of concentrating the fermented yulmu,
The extract is characterized in that the alcohol content based on the total weight of the extract of 12 to 16% by weight, the method for producing a fermentation rate-containing extract for the prevention and treatment of rheumatoid arthritis. The fermentation step is characterized in that the fermentation by adding 5 to 18 parts by weight of Nuruk and 0.5 to 5 parts by weight of Bio Nuruk and Saccharomyces cerevisiae with respect to 100 parts by weight of the steamed radish , Method for producing fermented yeast containing extract for the prevention and treatment of rheumatoid arthritis. delete An extract containing fermentation rate of radish for the prophylaxis and treatment of rheumatoid arthritis, prepared by the method according to claim 7 or 8. delete

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