JP5562986B2 - Preventive or ameliorating agent for lifestyle-related diseases - Google Patents

Description

  The present invention relates to a preventive or ameliorating agent for lifestyle-related diseases.

  In recent years, there has been a strong medical and sociological demand for preventing or improving lifestyle-related obesity, hyperlipidemia, and the like (lifestyle-related diseases). In recent years, various proposals have been made as such preventive or ameliorating agents (Patent Document 1, etc.), but development of new drugs capable of preventing or ameliorating lifestyle-related diseases is still required. Yes.

JP 2002-308766 A

  An object of the present invention is to provide a novel preventive or ameliorating agent for lifestyle-related diseases.

  The inventors of the present invention are those that contain an inulin-containing plant and a specific metabolic extract as active ingredients, and obesity or hyperlipidemia (particularly hypercholesterolemia) derived from lifestyle habits (for example, eating habits). , Hypertriglyceridemia) and the like were found to be effective for prevention or improvement.

  That is, according to the present invention, a plant (component A) containing inulin and a culture obtained by coculturing a mixed microorganism containing a plurality of lactic acid bacteria in a medium containing beans or a processed product thereof (component B) are effective. A preventive or ameliorating agent for lifestyle-related diseases, which is contained as a component, is provided.

  According to the present invention, it is possible to provide a novel preventive or ameliorating agent for lifestyle-related diseases that contains both components A and B as active ingredients.

Hereinafter, the present invention will be described in detail.
In the present invention, “lifestyle-related diseases” are based on the opinion statement “Basic direction of disease countermeasures focusing on lifestyle habits” of the Public Health Council (December 18, 1996). It refers to a group of diseases in which lifestyle habits such as eating habits, exercise habits, rest, smoking, and drinking are related to the onset and progression. Lifestyle-related diseases include obesity, obesity, diabetes, hyperlipidemia, hypertension, gout, high body fat percentage, hyperglycemia, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia, hypertension, and high Examples include uricemia. In lifestyle-related diseases, these are not a single disease but are related to each other.

  In the present invention, “prevention of hyperlipidemia” refers to the state of hyperlipidemia or borderline condition defined by the Japanese Society for Arteriosclerosis in the Guidelines for the Treatment of Atherosclerotic Diseases (issued in September 2002). It refers to preventing or delaying. Further, “improvement of hyperlipidemia” refers to bringing the hyperlipidemia state or boundary region state described above closer to the state defined as the normal region in the above guidelines.

  In the present invention, “prevention of diabetes” means preventing or delaying the state of diabetes or borderline defined by the Diabetes Society of Japan 2002-2003 (issued in May 2002). Point to. Further, “improving diabetes” refers to bringing the above-mentioned diabetes state or boundary state closer to the state defined as the normal region by the guide.

  In the present invention, “prevention of obesity” is a state defined by the Japanese Society of Obesity as obesity or obesity in the obesity / obesity instruction manual 2nd edition (issued in July 2001). Refers to preventing or delaying. Further, “improvement of obesity” means that the state defined by the academic society as obesity or obesity approaches the state defined by the academic society as a normal range.

  Component A, which is one of the active ingredients of the present invention, is a plant containing inulin. The inulin contained in this plant is a polysaccharide and is a member of the sugar, but the human body does not have an enzyme capable of degrading it and is not absorbed by the body.

  Examples of plants containing inulin include chrysanthemums such as chrysanthemums and dahlia, but chrysanthemums are preferred. Kikumo usually contains around 60% of inulin, which is said to be natural insulin.

  By containing a plant containing inulin, the effect of regulating the intestines, the effect of suppressing the increase in blood sugar level, insulin, and neutral lipid can be expressed. The expression mechanism is not clear, but is presumed as follows. Inulin contained in chrysanthemum buds undergoes the action of a hydrolase enzyme called inulase contained in the rhizome when processing rhizomes of chrysanthemum plants such as chrysanthemum buds, and changes to fructooligosaccharides. Inulin is easily converted into fructooligosaccharides by an acid such as gastric juice. The altered fructooligosaccharides are difficult to be used for harmful bacteria in the intestine due to their large molecular weight, and are used only for good bacteria (such as bifidobacteria) that are effective for intestinal adjustment. As a result, the growth of the good bacteria is promoted. It is thought that the intestinal effect is expressed. In addition, although fructooligosaccharides are saccharides, they are difficult to be absorbed because they are difficult to be absorbed by the body, and thus it is considered that they do not increase blood sugar levels or insulin, and also act to lower neutral lipids such as cholesterol.

  The chrysanthemums that can be used in the present invention may be wild chrysanthemums or normally grown chrysanthemums, but those that are grown without agricultural chemicals are desirable. The cultivation place can be preferably used as the chrysanthemum of the present invention if it grows normally, but if it is cultivated in a place where the temperature is 17 ° C. or less and the temperature difference is intense, the inulin content of the active ingredient increases. More preferable in terms.

  Chrysanthemum can be used in various forms such as ginger, boiled rice cake, raw powder, and dry powder, but from the viewpoint of storage, it is preferably used in the form of dry powder (powder, powder). It is more preferable that the powder particles be as fine as possible and used in the form of milk powder (for example, the particle diameter is about 10 μm or less). By making the powder particles as fine as possible, an effect like a microcapsule can be expected.

  Component B, which is one of the active ingredients of the present invention, is a specific culture. This culture is obtained by culturing (co-cultivating) a mixed microorganism containing a plurality of lactic acid bacteria in a medium containing beans. The culture includes not only the culture itself but also a processed product of the culture (details will be described later).

Examples of lactic acid bacteria include microorganisms belonging to the genus Bifidobacterium, microorganisms belonging to the genus Lactobaciilus, microorganisms belonging to the genus Enterococcus, microorganisms belonging to the genus Lactobacillus, and the like. These microorganisms are exemplified below.
(1) Microorganisms belonging to the genus Bifidobacterium:
B. longum, B. adolescentis, B. bifidum, etc.
(2) Microbes belonging to the genus Lactobaciilus:
Lactobacillus casei (for example, L. casei strain shirota), Lactobacillus paracasei, Lactobacillus bulgaricus, Lactobacillus acidophilus, etc.
(3) Microorganisms belonging to the genus Enterococcus:
Enterococcus faecium, E. faecalis, etc.
(4) Microorganisms belonging to the genus Lactobacillus:
For example, sporic lactic acid bacteria.
In the present invention, the microorganisms exemplified above can be used singly or in appropriate combination of two or more. Although the said microorganisms can use what is marketed generally, as long as the cultivated culture of these microorganisms or its processed material can be utilized as food-drinks etc., it is not limited to the specific strain | stump | stock of the said microorganisms.

  In the present invention, at least several tens of lactic acid bacteria described above are selected and mixed to form a mixed microorganism. Examples of the combination of mixed microorganisms include, for example, longum, addressentes and bifidum (hereinafter referred to as microorganisms belonging to the genus Bifidobacterium), paracasei and bulgaricus (hereinafter referred to as microorganisms belonging to the genus Lactobacillus), enterococcus faecium and fecalis ( As described above, a combination including a microorganism belonging to the genus Enterococcus and a spore-forming lactic acid bacterium (a microorganism belonging to the genus Lactobacillus) can be used.

The culture of the present invention can be obtained by culturing and fermenting such a mixed microorganism in a predetermined medium. A medium containing beans is used as the medium. Since beans contain a lot of essential amino acids, soy beans are especially called field meat and contain a lot of amino acids such as ferulalanine, tryptophan, lysine and threonine, and a lot of essential unsaturated fatty acids such as linoleic acid. Ingredients.
Examples of beans include soybeans and black beans, and these can be used alone or in combination of two or more. In the present invention, preferably, soybeans and black beans are selected from many beans, and the selected soybeans and black beans are boiled with, for example, hot water to obtain a stewed juice (hot water extract). The hot water extract of soybeans and black beans obtained in this way can be used as a medium in the present invention. In addition, the addition method to the culture medium of the selected soybean and black bean is not limited to the form of a hot-water extract, It can also be set as the non-heating form.

  And after mixing each of several lactic acid bacteria 200-1000 piece / ml per lactic acid bacterium, the mixed microorganisms are inoculated in the said culture medium, and cocultivate at 30-60 degreeC for a half year to one year. When cocultured, metabolites of lactic acid bacteria are produced in the medium. After completion of the culture, the culture is recovered by boiling sterilization, for example.

  In the present invention, the cultured culture itself after culturing is freeze-dried or spray-dried, for example, and the culture supernatant and cells separated by treatment such as filtration or centrifugation are freeze-dried or spray-dried, for example. What was prepared may be used as an active ingredient. However, preferably, a metabolic extract extracted from the treated product of the cultured product (for example, a cultured product (fermented product of soybeans and black beans) after culturing, that is, extracted by aging the metabolites of lactic acid bacteria produced in the medium. Extract) is preferably used as an active ingredient. This metabolic extract contains nucleic acids (soybean and black soybean DNA). The metabolic extract containing such nucleic acids can be used in various forms. For example, it is preferable to use a butyric acid type powder obtained by culturing butyric acid bacteria together with the above-mentioned plurality of lactic acid bacteria, and using this as a powder. .

  Most of the lactic acid bacteria contained in fermented foods are live bacteria, weak against heat and acid, and even if you eat live lactic acid bacteria, it is only a few that reaches the intestines due to the effect of stomach acid in the stomach, Metabolic extracts (including nucleic acids) extracted from fermented soybeans and black beans, which are examples of cultures, especially processed products of the above cultures, are resistant to acids because they enhance fermentation from amino acids to peptide dominance. Can reach the intestines. As a result, essential amino acids and unsaturated fatty acids that cannot be synthesized in the human body are supplied, and the intestinal environment is maintained. Since about 60% of autoimmunity is intestinal immunity, enhancement of immunity leads to prevention and improvement of lifestyle-related diseases. That is, the effect of prevention or improvement of lifestyle-related diseases can be expressed by including the culture or the processed product thereof.

  The preventive or ameliorating agent for lifestyle-related diseases according to the present invention is, for example, a chrysanthemum powder that is formed by thoroughly washing chrysanthemum, which is an example of a plant containing inulin, and slicing and drying it, It can be obtained by preparing a powder prepared by powdering the above-mentioned specific soybean fermented metabolic extract and blending these chrysanthemum powder and soybean fermented metabolic extract powder.

  The total content of active ingredients (= component A + component B) contained in the preventive or ameliorating agent for lifestyle-related diseases according to the present invention is preferably 50 to 100% by weight in terms of dry weight in the preventive or ameliorating agent. More preferably, it is 75 to 100% by weight.

  The content ratio (A / B) between component A and component B in the active ingredient is preferably 1.5 or more, more preferably 2.0 or more, preferably 3.5 or less, in terms of dry weight. More preferably 3. It is as follows. If the value of the content ratio (A / B) in the active ingredient is too small, the content of the ingredient A is relatively too small. Expression cannot be expected. On the other hand, if the value of the content ratio in the active ingredient is too large, the content of component B is relatively too small, and as a result, the above-described immunity enhancing effect cannot be expected.

  The shape of the preventive or ameliorating agent for lifestyle-related diseases according to the present invention (for example, an inhibitor of blood glucose level elevation, a prophylactic or ameliorating agent for obesity, a prophylactic or ameliorating agent for hyperlipidemia, etc.) If it is contained as an active ingredient, it will not specifically limit, For example, a powder, a granule, a tablet (tablet), a syrup agent, a drink agent etc. are mentioned. In order to obtain a tablet form, a direct tableting method in which the raw material powder in which Component A and Component B are mixed may be used as it is. In this direct method, the process is simple, but if the flowability of the raw material powder is poor, the weight may vary and the finish may be poor. Therefore, it is preferable to add the additive such as an excipient or a binder to the raw material powder obtained by mixing the component A and the component B, and then form into a tablet by a granule tableting method in which a tablet is formed after granulation. .

  Moreover, the preventive or ameliorating agent for lifestyle-related diseases according to the present invention comprises a food, a quasi-drug, and a material that can be used for a drug, a food for specified health use, a functional food, a health food, a quasi-drug In addition, it can be used after being processed into pharmaceutical products.

  The intake / frequency of intake of the preventive or ameliorating agent for lifestyle-related diseases according to the present invention is preferably 1.5 g or more, more preferably 2 g or more, preferably 3.5 g or less, per adult per day. Preferably it is 3 g or less, and it is preferable to carry out by dividing into 1 to several times.

  The intake period of the preventive or ameliorating agent for lifestyle-related diseases according to the present invention is preferably 6 months or longer, more preferably 12 months or longer, for subjects aiming at prevention of lifestyle-related diseases. In addition, in a subject suspected of having a lifestyle-related disease (preliminary army for lifestyle-related disease), 3 months or more is preferable, and 12 months or more is more preferable. Moreover, 6 months or more are preferable and 12 months or more are more preferable in the object (severely severe lifestyle-related diseases) aiming at improvement of lifestyle-related diseases. Further, the intake frequency per week is preferably 5 days or more, and more preferably 6 days or more.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[Example 1] Preparation of preventive or ameliorant sample As component A, a commercially available chrysanthemum candy was washed, sliced and dried, and then pulverized to prepare chrysanthemum powder (particle size of about 5 to 10 μm). . As a component B, a metabolic extract extracted from a culture (fermented product of soybean and black beans) obtained by culturing butyric acid bacteria together with 16 strains of lactic acid bacteria including 3 strains and 7 strains shown below in a medium containing soybean and black beans Nucleic acid powder (butyric acid type powder, particle size of about 10 to 100 μm) as a powder was prepared.
<Types of lactic acid bacteria>
-Longum, Addresses and Bifidham (microorganisms belonging to the genus Bifidobacterium).
Paracasei and bulgaricus (microorganisms belonging to the genus Lactobacillus).
Enterococcus faecium and faecalis (microorganisms belonging to the genus Enterococcus above).
Next, the preventive or improving agent of the present invention is prepared by blending the prepared chrysanthemum powder and nucleic acid powder so that the content ratio in terms of weight is 2.0 (chrysanthemum powder: nucleic acid powder = 2: 1). As an example, 5 kg of mixed powder was obtained.

[Example 2] Blood glucose level increase suppression test 15 Japanese (female and male) over 40 years old were subjects. Each subject was allowed to take the mixed powder of Example 1 at a daily intake frequency of 1 to 2 g for 3 months at a daily intake frequency, and blood glucose levels before and after intake (standard value range 70 to 110 mg / dl) was measured. The results are shown in Table 1.

About blood glucose level before ingestion, 3 subjects of 110 mg / dl or less, 5 subjects of 111-124 mg / dl, 1 subject of 125-150 mg / dl, 5 subjects of 151-200 mg / dl, There were one subject at 200 to 250 mg / dl, but after ingesting these, six subjects at 110 mg / dl or less, five subjects at 111-124 mg / dl, 125-150 mg / dl There were 3 subjects, 151 to 200 mg / dl subjects, and 0 200 mg / dl subjects. Specifically, there were 7 diabetic subjects (126 mg / dl or more) before ingestion but decreased to 4 after ingestion, and severe subjects (over 200 mg / dl) improved to 0 did. In particular, 6 subjects who were 150 mg / dl or more before ingestion decreased to 1 after ingestion, and 80% of subjects who had high blood glucose level (110 mg / dl or more) before ingestion, Reduced to 60%.
As described above, in this test group, it was confirmed that the blood glucose level significantly decreased before and after the intake of the mixed powder.

[Example 3] Hemoglobin AIC value increase suppression test Twenty-four Japanese (women and men) over 40 years old were subjects. Each subject was allowed to take the mixed powder of Example 1 at a daily intake frequency of 1 to 2 g for 3 months at a daily intake frequency. Hemoglobin AIC values before and after intake (standard value range 4 .3 to 5.8%). The results are shown in Table 2.

Regarding the hemoglobin AIC value before ingestion, 3 subjects with 110 mg / dl or less, 5 subjects with 111-124 mg / dl, 1 subject with 125-150 mg / dl, 5 subjects with 151-200 mg / dl , There were one subject of 200 to 250 mg / dl, but after ingestion, six subjects were 110 or less mg / dl or less, five subjects were 111 to 124 mg / dl, 125 to 150 mg / dl There were 3 subjects, 151-200 mg / dl subjects were 1 subject, and 200 mg / dl subjects were 0 subjects. In particular, the proportion of subjects who had high hemoglobin AIC values (more than 5.9%) before ingestion decreased from 87.5% to 66.7% after ingestion.
As described above, in this test group, it was confirmed that the hemoglobin AIC value significantly decreased before and after the intake of the mixed powder.

[Example 4] Cholesterol level elevation inhibition test Twelve Japanese (woman and man) over 40 years old were subjects. Each subject was allowed to take the mixed powder of Example 1 at a daily intake frequency of 1 to 2 g for 3 months at a daily intake frequency (standard value range 120 to 120). 220 mg / dl) was measured. The results are shown in Table 3.

Regarding cholesterol levels before ingestion, one subject was 170 to 200 mg / dl, one subject was 200 to 220 mg / dl, five subjects were 221 to 250 mg / dl, and five subjects were 251 to 270 mg / dl. However, after ingesting these, 2 subjects at 170 to 200 mg / dl, 5 subjects at 200 to 220 mg / dl, 4 subjects at 221 to 250 mg / dl, 251 to 270 mg / dl There was one subject. In particular, 10 subjects who had high cholesterol (220 mg / dl or more) before ingestion halved to 5 after ingestion.
As described above, in this test group, it was confirmed that the cholesterol level significantly decreased before and after the intake of the mixed powder.

[Example 5] Intraocular pressure increase suppression test 55 Japanese (female and male) over 40 years old were subjects. Each subject was allowed to take the mixed powder of Example 1 at a daily intake of 1 to 2 g and daily intake frequency for 2 to 3 months. The range is 10 to 20 mmHg, but 15 mmHg or less is desirable). The results are shown in Table 4.

Regarding the intraocular pressure value (right eye) before ingestion, 15 subjects were 15 mmHg or less, 31 subjects were 16-20 mmHg, 9 subjects were 21 mmHg or more, and 15 subjects were 15 mmHg or less for the left eye There were 15 subjects, 33 subjects who were 16-20 mmHg, and 7 subjects who were 21 mmHg or more. On the other hand, after ingestion, 34 subjects were 15 mmHg or less for the right eye, 19 subjects were 16-20 mmHg, 2 subjects were 21 mmHg or more, and 15 subjects were 15 mmHg or less for the left eye. There were 40 subjects, 14 subjects who were 16-20 mmHg, and 1 subject who was 21 mmHg or more.
In particular, a target intraocular pressure value of 15 mmHg or less was significantly improved from 15 before intake to 34 after intake for the right eye and from 15 before intake to 40 after intake for the left eye. The reason why such a significant improvement effect is obtained is not necessarily clear, but it is presumed to be due to the decrease in the cholesterol level of Example 4 and particularly due to the inulin contained in Component A.
In ophthalmology, diabetes was the leading cause of blindness until 1993, but glaucoma has been the first since 1994. One of the causes is retinal cholesterol, and the causal relationship between eyes and cholesterol is said to be important. Glaucoma is also considered a lifestyle-related disease.

[Example 6] Diet effect confirmation test The same 15 Japanese as in Example 2 were used as subjects. Each subject was allowed to take the mixed powder of Example 1 at a daily intake frequency of 1-2 g for 3 months, and the body weight before and after intake was measured. As a result, a weight reduction effect of 1 to 4 kg was confirmed for all 15 people after ingestion compared to before ingestion. From the above, in this test group, it was confirmed that the body weight significantly decreased before and after the intake of the mixed powder.
Insulin is thought to take carbohydrates into the human body as energy in the form of glycogen, but excess carbohydrates can be obese because they are stored in the body as body fat. The reason why the diet effect was confirmed in this example is presumed to be due to the removal of sugar by the inulin effect.

[Example 7] Fecal property confirmation test and fecal effect confirmation test Fifteen Japanese people as in Example 2 were subjects. Each subject was allowed to take the mixed powder of Example 1 at a daily intake frequency of 1 to 2 g for 3 months at a daily intake frequency, and the odor of the stool before and after the intake was evaluated. As a result, it was confirmed that the odor of stool disappeared for all 15 people after ingestion compared to before ingestion. This is presumed to be due to the fact that the good bacteria of the intestinal flora are surely increasing, and that the gas-producing bacteria, Escherichia coli and Welsh bacteria, which are the source of malodor, are suppressed.
In addition, the same amount was consumed at the same intake frequency for the same period, and the bowel movement before and after the intake was evaluated. As a result, the bowel movement effect was improved for all 15 people after ingestion compared to before ingestion. This is presumed that since both component A and component B are water-soluble fibers, bowel movement is improved and constipation is improved.

[Example 8]
Under the same conditions as in Example 1, except that the chrysanthemum powder and the nucleic acid powder were blended so that the content ratio in terms of weight was 2.5 (chrysanthemum powder: nucleic acid powder = 2.5: 1) As an example, 15 kg of mixed powder was obtained. When the same test was performed using the obtained mixed powder under the same conditions as in Examples 2 to 7, the same effect was confirmed.

[Example 9]
As an example of a preventive or ameliorating agent under the same conditions as in Example 1 except that the chrysanthemum powder and nucleic acid powder were blended so that the content ratio in terms of weight was 3.0 (chrysanthemum powder: nucleic acid powder = 3: 1). Of 15 kg of mixed powder was obtained. When the same test was performed using the obtained mixed powder under the same conditions as in Examples 2 to 7, the same effect was confirmed.

Claims (5)

  Contains both powdered chrysanthemums (component A) and a culture obtained by co-culturing mixed microorganisms containing a plurality of lactic acid bacteria in a medium containing soybeans and black beans or a processed product thereof (component B) as active ingredients Prevention of lifestyle-related diseases in which the content ratio (A / B) of component A to component B in the active ingredient is 1.5 to 3.5 in terms of dry weight Or an improving agent. Treated product of the culture, No placement claim 1 Symbol including metabolic extract originating from the culture obtained by Force culturing a microorganism mixture including dozens kinds of lactic acid bacteria in a medium consisting of hot water extract of soybean and black beans Preventive or ameliorating agent. The preventive or ameliorating agent according to claim 2, wherein 16 strains of lactic acid bacteria including the following 3 types and 7 strains are used as lactic acid bacteria.
(1) Longum, Adrecentes and Bifidham (microorganisms belonging to the genus Bifidobacterium).
(2) Paracasei and bulgaricus (microorganisms belonging to the genus Lactobacillus).
(3) Enterococcus faecium and faecalis (microorganisms belonging to the genus Enterococcus above). The prevention or improvement agent comprised with the granule which granulated the mixed powder in any one of Claims 1-3 . A preventive or ameliorating agent obtained by tableting the mixed powder according to any one of claims 1 to 3 or the granule according to claim 4 into tablets.