JP2020180095A - Composition for reducing blood urine acid level, and composition for preventing or improving hyperuricemia, and pharmaceutical composition and food and drink composition including the composition - Google Patents

Abstract

To provide a new composition for reducing a blood urine acid level, and a new composition for preventing or improving hyperuricemia.SOLUTION: The present invention provides a composition for reducing a blood urine acid level, containing Bifidobacterium breve as an active ingredient. The present invention provides a composition for preventing or improving hyperuricemia, containing Bifidobacterium breve as an active ingredient. The composition for reducing a blood urine acid level and the composition for preventing or improving hyperuricemia can be used for a pharmaceutical composition and a food and drink composition.SELECTED DRAWING: None

Description

The present technology relates to a composition for reducing blood uric acid level, a composition for preventing or improving hyperuricemia, and a pharmaceutical composition and a food and drink composition using the composition.

Uric acid is the final product of metabolism of nucleic acids, ATP, which is an energy source in the living body, and purines derived from foods and drinks, and is mainly excreted from the kidneys. Various factors act on the pathway from uric acid production to excretion, and when uric acid production becomes excessive or excretion decreases, the uric acid level in the blood increases, resulting in hyperuricemia. Known factors for this include obesity, binge eating, drinking alcohol, excessive exercise (anaerobic exercise), and stress. Furthermore, hyperuricemia persists for a long period of time, and uric acid crystallizes and precipitates in joints and kidneys, causing gout. Due to changes in lifestyle such as eating habits in recent years, the number of gout patients is increasing in Japan, and the number of hyperuricemia patients who are considered to be gout reserves is also increasing.

Under these circumstances, there has been a demand for the development of drugs and compositions having an effect of reducing blood uric acid level and an effect of preventing or ameliorating hyperuricemia. It is known that conventional therapeutic agents for hyperuricemia are classified into two types: uric acid production inhibitor that prevents uric acid from being produced and uric acid excretion promoter that releases uric acid to the outside. The former suppresses uric acid production by inhibiting xanthine oxidase (XO), which is an enzyme required in the process of decomposing purines into uric acid. On the other hand, the latter promotes uric acid excretion by inhibiting a uric acid transporter molecule called URAT1 that is present in the proximal tubule of the kidney and performs uric acid reabsorption.

In addition, foods and drinks and supplements that can be ingested on a daily basis are also required, and lactic acid bacteria and bifidobacteria are attracting attention as their active ingredients. For example, Cited Document 1 discloses a preventive or ameliorating agent for hyperuricemia containing Bifidobacterium longum BB536 (ATCC BAA-999) as an active ingredient. Further, Cited Document 2 discloses a blood uric acid level reducing agent containing a specific type of lactic acid bacterium or bifidobacteria as an active ingredient.

JP-A-2009-143820 JP-A-2017-31102

As described above, although various proposals have been made for prevention and treatment methods for hyperuricemia, there are concerns about side effects in the method using synthetic compounds and the like. In addition, as in Patent Documents 1 and 2, some preventive and therapeutic methods by ingesting probiotic cells or fermented products have already been reported, but probiotics have different physiological actions for each strain. Is known to indicate, and consistent results have not been obtained.

Therefore, a main object of the present technology is to provide a new composition for reducing blood uric acid level and a composition for preventing or improving hyperuricemia.

That is, in the present technology, first, a composition for reducing blood uric acid level, which contains Bifidobacterium breve as an active ingredient, is provided.
The present technology also provides a composition for preventing or ameliorating hyperuricemia, which contains bifidobacteria breve as an active ingredient.
In the present technique, the Bifidobacterium breve can be Bifidobacterium bleve MCC1274 (FERM BP-11175).
In addition, the composition can be used as a pharmaceutical composition or a food or drink composition.

According to the present technology, it is possible to provide a new composition for reducing blood uric acid level and a composition for preventing or improving hyperuricemia.
The effects described here are not necessarily limited, and may be any of the effects described in the present specification.

Hereinafter, suitable embodiments for carrying out the present technology will be described.
It should be noted that the embodiments described below show an example of typical embodiments of the present technology, and the scope of the present technology is not narrowly interpreted by this.

1. 1. Composition for reducing blood uric acid level, and composition for preventing or improving hyperuricemia The composition for reducing blood uric acid level of the present technology, and the composition for preventing or improving hyperuricemia (hereinafter, simply "the present technology"). (Also referred to as "composition of") is characterized in that it contains bifidobacteria breve as an active ingredient.

Bifidobacterium breve is one of the species belonging to the genus Bifidobacterium. Bifidobacterium longum subsp. Infantis (Bifidobacterium longum subsp. Infantis) is mainly found in the large intestine of infants, and among the species belonging to the genus Bifidobacterium. ) Etc., and is known as an infant-type Bifidobacterium genus bacterium.

Since the active ingredient of the composition of this technology is Bifidobacterium breve, which mainly inhabits the large intestine of infants, it is excellent in safety and has side effects even if it is continuously administered for a long period of time. It is very useful because there is less need to worry about it. Furthermore, it is highly safe even when used in combination with other drugs.

In addition, if the uric acid level in the blood is suddenly lowered, the uric acid crystals that have accumulated in the joints may dissolve at once and cause a gout attack. Therefore, in the treatment of hyperuricemia, it is desirable not to lower the blood uric acid level in the short term, but to gradually lower it over a long period of time and maintain the target value for a long period of time. Since the composition of the present technology can be safely ingested for a long period of time, it is also useful when used for such a purpose.

Bacteria belonging to Bifidobacterium breve include, for example, Bifidobacterium bleve MCC1274 (FERM BP-11175), M-16V (NITE BP-02622), UCC2003, YIT4010, YIT4064, BBG-001, BR- 03, B632 (DSMZ 24706), C50, Bb99 (DSM 13692), R0070, ATCC15700, ATCC15698, DSM 24732, etc. Among these, Bifidobacterium Breve MCC1274 (FERM BP-11175) ) Is preferably used.

Bifidobacterium Breve MCC1274 is an Incorporated Administrative Agency Industrial Technology Research Institute Patent Organism Depositary Center (Japan 〒305-8566 1-1-1 Higashi, Tsukuba City, Ibaraki Prefecture Central 6th (currently IPOD Incorporated Administrative Agency Product Evaluation Technology Infrastructure) PMDA Patent Organism Depositary Center (NITE-IPOD): Japan 〒292-0818 2-5-8 Kazusakamatari, Kisarazu-shi, Chiba Room 120), IPOD FERM BP-11175 deposit number from August 25, 2009 It has been deposited at.

The strain specified by the above-exemplified strain name is not limited to the strain itself that has been deposited or registered with a predetermined institution under the strain name (hereinafter, also referred to as "deposited strain" for convenience of explanation). Substantially equivalent strains (also referred to as "derivative strains" or "derivative strains") are also included. That is, for example, "Bifidobacterium Breve MCC1274 (FERM BP-11175)" is not limited to the strain itself deposited with the above depository with the deposit number of MCC1274 (FERM BP-11175), and is substantially the same. Equivalent strains are also included. Regarding the strain, "a strain substantially equivalent to the above-mentioned deposit strain" belongs to the same species as the above-mentioned deposit strain, and has an effect of reducing blood uric acid level and an effect of preventing or improving hyperuricemia, which are the effects of this technology. Means a strain that can be obtained. The stock substantially equivalent to the deposited stock may be, for example, a derivative stock having the deposited stock as a parent stock. Derivative strains include strains bred from deposit stocks and strains naturally generated from deposit stocks.

Examples of substantially the same strains and derivative strains include the following strains.
(1) Strains determined to be the same strain by the RAPD method (Randomly Amplified Polymorphic DNA) and PFGE method (Pulsed-field gel electrophoresis) (described in Probiotics in food / Health and nutritional properties and guidelines for evaluation 85 Page 43)
(2) A strain that possesses only the gene derived from the deposited strain, does not have a gene derived from a foreign country, and has a DNA identity of 95% or more. (3) A strain bred from the strain (genetical engineering modification, mutation) , Including spontaneous mutations), strains with the same trait

In the present art, "improvement" means improvement of a disease, symptom or condition; prevention or delay of deterioration of the disease, symptom or condition; reversal, prevention or delay of progression of the disease or symptom. In addition, "prevention" means prevention or delay of the onset of a disease or symptom in the application target, or reduction of the risk of the disease or symptom in the application target.

The composition of the present technology is particularly effective in reducing the blood uric acid level, as shown in Examples described later. In addition, in this technique, "hyperuricemia" is a concept including the symptoms of gout and urethral stones caused by this.

The subject of the composition of the present technology is not particularly limited, and can be applied to animals including humans. In addition, the target gender, target age, etc. are not particularly limited. For example, men who consume a large amount of alcohol and purines from their diet and consume a small amount of vegetables, and adults who lack exercise can be mentioned. In addition, the composition of this technology should be used for infants and children, pregnant, perinatal and lactating women, and elderly and sick people at high risk of hyperuricemia due to its high safety. Can be done.

Even if the composition of the present technology contains a culture containing Bifidobacterium Breve MCC1274 (FERM BP-11175) as its active ingredient, Bifidobacterium Breve MCC1274 (FERM BP-11175). Good.

The medium for culturing Bifidobacterium breve used in the present technology is not particularly limited, and a medium usually used for culturing bacteria belonging to the genus Bifidobacterium can be used.

As the carbon source, for example, sugars such as glucose, galactose, lactose, arabinose, mannose, sucrose, starch, starch hydrolyzate, and waste sugar honey can be used depending on the assimilation property. As the nitrogen source, for example, ammonium salts such as ammonia, ammonium sulfate, ammonium chloride and ammonium nitrate and nitrates can be used. As the inorganic salts, for example, sodium chloride, potassium chloride, potassium phosphate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, ferrous sulfate and the like can be used. In addition, organic components such as peptone, soybean flour, defatted soybean meal, meat extract, and yeast extract may be used.

The culturing conditions are not particularly limited as long as the effects of the present technique are not impaired, but for example, the culturing temperature is usually 25 to 50 ° C., preferably 35 to 42 ° C. Further, the culture is preferably carried out under anaerobic conditions, and for example, the culture can be carried out while aerating an anaerobic gas such as carbon dioxide gas. Further, the cells may be cultured under microaerobic conditions such as liquid static culture.

As the bifidobacteria breve used in the present technology, the obtained culture may be used as it is after culturing, diluted or concentrated, or bacterial cells recovered from the culture may be used. .. The term "culture" in the present specification is a concept including a culture supernatant.

As the present cells, the obtained culture after culturing may be used as it is, diluted or concentrated, or the cells recovered from the culture may be used. In addition, various additional operations such as heating and freeze-drying can be performed after culturing as long as the effects of the present technology are not impaired. In addition, this bacterial cell may be a live bacterium or a dead bacterium. In the case of viable bacteria, it is preferable to treat them by a bacterial solution freezing method, a spray drying method, a freeze drying method, or an oil drop method. Examples of killed bacteria include killed bacteria that have been sterilized by heating, freeze-drying, or the like. Other methods for preparing dead cells include spray drying method (spray drying method), retort sterilization method, freeze sterilization method, UHT sterilization method, pressure sterilization method, high pressure steam sterilization method, dry heat sterilization method, and distribution steam sterilization method. , Electromagnetic sterilization method, electron beam sterilization method, high frequency sterilization method, radiation sterilization method, ultraviolet sterilization method, ethylene oxide gas sterilization method, hydrogen peroxide gas plasma sterilization method, chemical sterilization method (alcohol sterilization method, formalin fixation method, electrolysis) Water treatment method) and the like. In addition, this bacterial cell may be a crushed product. The crushed product may be one in which live bacteria are crushed, one in which dead bacteria are crushed, or one in which heating, freeze-drying, or the like is performed after crushing. Further, for crushing, crushing by a method and equipment known in the art, for example, physical crushing, enzyme dissolution treatment, chemical treatment, autolysis treatment and the like can be selected.

The physical crushing may be carried out by either a treatment in the state of a cell suspension or a treatment in the state of a cell powder. Examples of physical crushing include crushing by stirring using an ultrasonic homogenizer, homogenizer, ball mill, bead mill, dyno mill, planetary mill, etc., crushing by pressure using a jet mill, French press, cell crusher, etc., filter filtration treatment. You can choose to crush by damaging the cells. As the enzyme lysis treatment, for example, an enzyme such as lysozyme can be used to destroy the cell structure of the cells. As the chemical treatment, for example, a surfactant such as soybean phospholipid or glycerin fatty acid ester can be used to destroy the cell structure of the cells. As the autolysis treatment, for example, the cells can be dissolved by the enzyme of some lactic acid bacteria themselves. In this technique, physical crushing is preferable because it is not necessary to add other chemicals or compounds.

The composition of the present technology may be composed of only the active ingredient, or may be a composition in which the active ingredient and an arbitrary ingredient other than the active ingredient are blended. The optional component is not particularly limited as long as the effect of the present technology is not impaired, and an additive conventionally blended in a pharmaceutical product (for example, a formulation carrier described later) can be blended.

2. Specific forms of the composition of the present technology The composition of the present technology can be used in various forms such as foods and drinks, pharmaceuticals, quasi-drugs, and feeds.

The use of this embodiment may be for therapeutic purposes or for non-therapeutic purposes. "Non-therapeutic purpose" is a concept that does not include medical practice, that is, treatment of the human body by treatment, and examples thereof include health promotion and cosmetology.

<Food and drink>
A food or drink composition using the composition of the present technology (hereinafter, also simply referred to as "food and drink composition of the present technology") can be prepared by adding to a known food or drink, or is used as a raw material for food or drink. It can also be mixed with and manufactured as a new food or drink.

The food and drink composition of the present technology may be in the form of liquid, paste, solid, powder, etc., in addition to confectionery, liquid food, etc., for example, flour products, instant foods, processed agricultural products, processed marine products, livestock products. Examples include processed products, milk / dairy products, oils and fats, basic seasonings, complex seasonings / foods, frozen foods, confectionery, beverages, and other commercial products.

Examples of wheat flour products include bread crumbs, macaroni, spaghetti, noodles, cake mixes, fried chicken flour, bread crumbs and the like.
Examples of instant foods include instant noodles, cup noodles, retort / cooked foods, canned foods, microwave foods, instant soups / stews, instant miso soup / soups, canned soups, freeze-dried foods, and other instant foods. Be done.
Examples of processed agricultural products include canned agricultural products, canned fruits, jams and marmalades, pickles, boiled beans, dried agricultural products, cereals (processed grain products), and the like.
Examples of processed marine products include canned marine products, fish hams and sausages, fish paste products, marine delicacies, and boiled fish.
Examples of processed livestock products include canned livestock and pastes, livestock ham and sausage.
Examples of milk and dairy products include fermented milk such as yogurt, processed milk, dairy beverages, lactic acid bacteria beverages, cheese, ice creams, formula milk powder, cream, infant formula, infant nutritional supplements, and pregnant women.・ Milk for mothers of lactating women and other dairy products.
Examples of fats and oils include butter, margarines, vegetable oils and the like.
Examples of the basic seasonings include soy sauce, miso, sauces, processed tomato seasonings, mirins, vinegars and the like, and the compound seasonings / foods include cooking mixes, curry ingredients, sauces, etc. Examples include dressings, mentsuyu, spices, and other complex seasonings.
Examples of the frozen food include raw material frozen food, semi-cooked frozen food, and cooked frozen food.
Examples of confectioneries include caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese confectionery, rice confectionery, bean confectionery, dessert confectionery, and other confectionery.
Beverages include, for example, carbonated beverages, natural fruit juices, fruit juice beverages, soft beverages containing fruit juice, fruit meat beverages, fruit beverages containing fruit grains, vegetable beverages, soy milk, soy milk beverages, coffee beverages, tea beverages, powdered beverages, concentrated beverages, etc. Examples include sports beverages, nutritional beverages, alcoholic beverages, and other favorite beverages.
Examples of commercially available foods other than these include baby food, sprinkle, ochazuke seaweed and the like.

The food and drink composition of the present technology can be produced by adding the cells to the raw materials of ordinary foods and drinks, and is produced in the same manner as ordinary foods and drinks except that the cells are added. be able to. The addition of the cells may be carried out at any stage of the manufacturing process of the food or drink composition. In addition, a food or drink composition may be produced through a fermentation step using the added bacterial cells. Examples of such food and drink compositions include lactic acid bacteria beverages and fermented milk.

As a raw material for the food and drink composition of the present technology, a raw material used for ordinary food and drink can be used. The food and drink composition produced can be ingested orally.

Further, for example, it is also possible to adopt a method in which the cells are added to milked breast milk and ingested orally, or a method in which a newborn baby or an infant is ingested by a nasogastric feeding tube or the like.

In addition, in the food and drink composition of the present technology, as long as the effect of the present technology is not impaired, a component having a known or future probiotic effect or a component assisting the probiotic effect shall be used. Can be done.

Specifically, for example, various proteins such as whey protein, casein protein, soybean protein, or pea protein (pea protein) or mixtures thereof, decomposition products; amino acids such as leucine, valine, isoleucine or glutamine; vitamin B6 or vitamins. Vitamins such as C; creatin; citric acid; fish oil; or with components such as isomaltooligosaccharides, galactooligosaccharides, xylooligosaccharides, soybean oligosaccharides, fructo-oligosaccharides, lactulose, and oligosaccharides such as human milk oligosaccharides (HMO). It can be produced by blending with this bacterial cell.

Examples of human milk oligosaccharides include 2'-fucosyl lactose, 3-fucosyl lactose, 2', 3-difucosyl lactose, lacto-N-triose II, lacto-N-tetraose, lacto-N-neotetraose, and the like. Lactose-N-fucopentaose I, lacto-N-neofcopentaose, lacto-N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-fucopentaose V, lacto-N-neofcopentaose V, lacto-N Neutral human milk oligosaccharides such as -difucohexaose I, lacto-N-difucohexaose II, 6'-galactosyl lactose, 3'-galactosyl lactose, lacto-N-hexaose and lacto-N-neohexaose Examples thereof include acidic human milk oligosaccharides such as 3,'-sialyl lactose, 6'-sialyl lactose, 3-fucosyl-3'-sialyl lactose, and disialyl-lacto-N-tetraose.

The content of Bifidobacterium breve MCC1274 (FERM BP-11175) in the food and drink composition of the present technology can be freely set as long as the effect of the present technology is not impaired. In the present technology, in particular, the content of Bifidobacterium breve MCC1274 (FERM BP-11175) in the food or drink composition is 1 × 10 ³ to 1 × 10 ^{12 with} respect to the final composition of the food or drink composition. It is more preferable to contain cfu / g. The daily dose is at least 1 × 10 ³ cfu / day, more preferably 1 × 10 ⁶ cfu / day or more, more preferably 1 × 10 ⁸ cfu / day or more, more preferably 2 × 10 ¹⁰ It is preferable to add cfu / day or more, or more. In this technique, in particular, per serving, it is preferable to Bifidobacterium breve MCC1274 the (FERM BP-11175) to include ¹⁰ 6 ^{~10 12} cfu. In addition, "cfu" represents a colony forming unit (colony forming unit). When the cells are dead, cfu / g or cfu / ml can be replaced with individual cells / g or individual cells / ml. When this cell is a crushed product, it can be displayed in terms of weight from the number of bacteria (individual cells / g) before crushing.

[Foods with health claims / special purpose foods]
The composition can be applied to foods with health claims and foods for special purposes. The health functional food system was established not only for ordinary foods but also for foods in the shape of tablets, capsules, etc., based on internal and external trends and consistency with the conventional food system for specified health uses. There are three types of foods: foods for specified health use, foods with functional claims, and foods with nutritional function. Special-purpose foods are foods for special purposes for people who cannot eat normal meals, such as sick people, infants, and the elderly, and foods for the sick (permission standard type, individual evaluation). Type), milk powder for pregnant and lactating women, adjusted milk for infants, and foods for people with swallowing difficulties.

The composition is not limited to the following description, but the composition includes, for example, low purine foods for those with increased uric acid levels, low protein foods for those with decreased renal function, and individual evaluation type foods. It can be applied to foods for the sick, or it can be applied to foods with functional claims targeting healthy people, people in the normal high range of uric acid level index, and people in the mild range.

In addition, as a food and drink composition of the present technology, milk powder prepared for infants can be mentioned. "Prepared milk for infants" means prepared milk for infants from 0 to 12 months, follow-up milk for infants from 6 to 9 months and younger children (up to 3 years old), and birth. Prepared milk powder for low birth weight infants (low birth weight infants) who weigh less than 2500 g at the time, various therapeutic milks used for the treatment of infants with morbidity such as milk allergy and lactose intolerance. And so on.

Food and beverage compositions of this technology include nutritionally-adjusted foods such as mom's milk for mothers during pregnancy and lactation (prepared milk powder with a well-balanced mixture of nutrients required for pregnancy and lactation), and adjusted milk for adults. Examples thereof include nutritional supplements, nutritional functional foods such as liquid foods, and foods for the sick (special purpose foods) such as phosphorus-reduced powdered milk.

The prepared milk powder can be produced, for example, by the following method.

That is, in this technique, bacterial cell powder containing Bifidobacterium spp. Is mixed with prebiotics and / or milk powder for reducing blood uric acid level, or for preventing or improving hyperuricemia. Provided is a method for producing milk powder for infants or milk for moms to obtain milk powder.

Specifically, for example, a method for producing milk powder for enhancing breast milk components, which comprises the following steps (A) to (C):
(A) A step of culturing a bacterium belonging to the genus Bifidobacterium in a medium containing a milk component to obtain a culture;
(B) A step of subjecting the culture to spray drying and / or freeze-drying to obtain bacterial cell powder;
(C) A step of mixing the cell powder with prebiotics and / or milk powder to obtain milk powder for reducing blood uric acid level or preventing or improving hyperuricemia.

〔supplement〕
In addition, the food and drink composition of the present technology may be a supplement for reducing blood uric acid level or for preventing or improving hyperuricemia.

Supplements for reducing blood uric acid levels or for preventing or improving hyperuricemia can be produced, for example, by the following methods.

That is, the present technology provides, for example, a method for producing a supplement for reducing blood uric acid level or for preventing or improving hyperuricemia, which comprises the following steps (A) and (B):
(A) A step of mixing prebiotics, Bifidobacterium spp., And excipients to obtain a mixture;
(B) A step of locking the mixture.

[Food and drink with functional indication]
In addition, the food and drink composition defined in the present technology can be provided and sold as food and drink having a specific use (particularly for health use) and a function.

The "display" act includes all acts for informing the consumer of the use, and if it is an expression that can recall or infer the use, the purpose of the display, the content of the display, and the display Regardless of the object, medium, etc., all fall under the "display" act of this technology.

Further, the "display" is preferably performed by an expression that allows the consumer to directly recognize the above-mentioned use. Specifically, the act of transferring a product related to food and drink or the packaging of the product with the above-mentioned use, displaying it for delivery, transfer or delivery, and importing it, advertising on the product, price list or transaction documents Examples include the act of describing the above-mentioned use and displaying or distributing it, or describing the above-mentioned use in the information containing these and providing it by an electromagnetic (Internet, etc.) method.

On the other hand, as the display content, it is preferable that the display is approved by the government or the like (for example, a display obtained based on various systems established by the government and performed in a manner based on such approval). In addition, it is preferable to attach such display contents to packaging, containers, catalogs, pamphlets, promotional materials such as POPs at sales sites, and other documents.

In addition, "labeled" includes health foods, functional foods, foods for the sick, enteral nutrition foods, special purpose foods, health functional foods, specified health foods, functional labeled foods, nutritionally functional foods, and pharmaceutical departments. Labeling as a foreign product can also be mentioned. Among these, in particular, labeling approved by the Consumer Affairs Agency, for example, a food system for specified health use, a food system with functional labeling, and labeling approved by a system similar to these can be mentioned. More specifically, labeling as food for specified health use, labeling as conditional food for specified health use, labeling as functional food, labeling indicating that it affects the structure and function of the body, labeling for reducing disease risk, etc. Can be mentioned. Among these, as a typical example, labeling as a food for specified health use stipulated in the Health Promotion Law Enforcement Regulations (April 30, 2003, Ministry of Health, Labor and Welfare Ordinance No. 86) (especially labeling for health uses) , The labeling as a food with functional claims stipulated in the Food Labeling Law (Law No. 70 of 2013) and the labeling similar to these.

In addition, the wording used for displaying as described above is not only the wording such as reduction of blood uric acid level and prevention or improvement of hyperuricemia, but also other words such as blood uric acid level. Needless to say, any wording that expresses the effect of prevention, treatment and / or improvement of various diseases and symptoms related to reduction and prevention or improvement of hyperuricemia is included in the scope of the present technology. Such words include, for example, "for those who are concerned about blood uric acid level", "for those who are concerned about high blood uric acid level", and "for those who are concerned about hyperuricemia". It is also possible to display based on various uses such as the effect of reducing blood uric acid level and the effect of preventing or improving hyperuricemia. It is also possible to display the blood uric acid level reducing effect and the hyperuricemia prevention or improving effect based on the results evaluated using the new uric acid level measuring method.

<Pharmaceuticals, quasi-drugs>
A pharmaceutical composition or a quasi-drug composition using the composition of the present technology (hereinafter, also simply referred to as "composition of a pharmaceutical product, etc. of the present technology") is a known pharmaceutical product or quasi-drug (hereinafter, "pharmaceutical product, etc." It can be prepared by adding it to (also referred to as)), or it can be mixed with a raw material of a drug or the like to produce a new drug or the like.

When the composition of the present technology is used for a composition such as a pharmaceutical product, the composition can be appropriately formulated into a desired dosage form according to an administration method such as oral administration or parenteral administration. The dosage form is not particularly limited, but in the case of oral administration, for example, solid preparations such as powders, granules, tablets, troches, capsules; preparations in liquid preparations such as solutions, syrups, suspensions and emulsions. Can be transformed into. In the case of parenteral administration, it can be formulated into, for example, a suppository, a spray, an inhalant, an ointment, a patch, an injection, or the like. In the present technology, it is preferable to formulate the dosage form for oral administration. The formulation can be carried out by a known method as appropriate according to the dosage form.

At the time of formulation, a formulation carrier may be appropriately added to the formulation. In addition to the composition of the present technology, components such as excipients, pH adjusters, colorants, and flavoring agents that are usually used for formulation can be used. Furthermore, components having a preventive, ameliorating and / or therapeutic effect on diseases and symptoms known or found in the future can be appropriately used in combination as long as the effects of the present technology are not impaired.

As the preparation carrier, various organic or inorganic carriers can be used depending on the dosage form. Examples of the carrier in the case of a solid preparation include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents and the like.

Examples of excipients include sugar derivatives such as lactose, sucrose, glucose, mannit, and sorbit; starch derivatives such as corn starch, horse bell starch, α-starch, dextrin, and carboxymethyl starch; crystalline cellulose, hydroxypropyl cellulose, etc. Cellulose derivatives such as hydroxypropylmethyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose calcium; gum arabic; dextran; purulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, magnesium aluminometasilicate; phosphate derivatives such as calcium phosphate; carbonic acid Carbonated carbonate derivatives such as calcium; sulfate derivatives such as calcium sulfate can be mentioned.

Examples of the binder include gelatin; polyvinylpyrrolidone; macrogol, etc., in addition to the above-mentioned excipients.

Examples of the disintegrant include, in addition to the above-mentioned excipients, chemically modified starch or cellulose derivatives such as croscarmellose sodium, carboxymethyl starch sodium, and crosslinked polyvinylpyrrolidone.

Examples of the lubricant include talc; stearic acid; metal stearic acid salts such as calcium stearate and magnesium sulfate; colloidal silica; waxes such as pea gum and gay wax; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid. Sodium carboxylic acid salts such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicates such as silicic acid anhydride and silicate hydrate; starch derivatives and the like. Be done.

Examples of the stabilizer include paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalconium chloride; acetic acid anhydride; and sorbic acid.

Examples of the flavoring and flavoring agent include sweeteners, acidulants, and flavors.

In addition, examples of the carrier used in the case of a liquid preparation for oral administration include a solvent such as water, a flavoring and odorant, and the like.

The content of Bifidobacterium Breve MCC1274 (FERM BP-11175) in the pharmaceutical composition of the present technology can be freely set as long as the effect of the present technology is not impaired. In the present technology, in particular, the content of Bifidobacterium breve MCC1274 (FERM BP-11175) in the composition of a pharmaceutical product is 1 × 10 ³ to 1 × 10 ^{12 with} respect to the final composition of the composition of a pharmaceutical product. It is more preferable to contain cfu / g. The daily dose is at least 1 × 10 ³ cfu / day, more preferably 1 × 10 ⁶ cfu / day or more, more preferably 1 × 10 ⁸ cfu / day or more, more preferably 2 × 10 ¹⁰ It is preferably cfu / day or more, or more. In this technique, in particular, per package, it is preferable to Bifidobacterium breve MCC1274 the (FERM BP-11175) to include ¹⁰ 6 ^{~10 12} cfu.

<Feed>
The feed using the composition of the present technology can be prepared by adding it to a known feed, or it can be mixed with the feed material to produce a new feed.

When the composition of this technology is used for feed, the feed raw materials include, for example, cereals such as corn, wheat, barley, and rye; bran such as bran, wheat bran, rice bran, and defatted rice bran; corn gluten meal, corn jam. Production grains such as meal; animal feeds such as defatted milk powder, whey, fish flour, bone meal; yeasts such as beer yeast; mineral feeds such as calcium phosphate and calcium carbonate; fats and oils; amino acids; sugars and the like. .. Examples of the feed form include pet food (pet food, etc.), livestock feed, fish feed, and the like.

The content of Bifidobacterium breve MCC1274 (FERM BP-11175) in the feed of the present technology can be freely set according to the body weight and the like as long as the effect of the present technology is not impaired. In this technique, in particular, the content of Bifidobacterium breve MCC1274 (FERM BP-11175) in the feed is 1 × 10 ³ to 1 × 10 ¹² cfu / g with respect to the final composition of the feed. Is more preferable. The daily dose is at least 1 × 10 ³ cfu / day, more preferably 1 × 10 ⁶ cfu / day or more, more preferably 1 × 10 ⁸ cfu / day or more, more preferably 2 × 10 ¹⁰ It is preferably cfu / day or more, or more.

The present technology can also adopt the following configurations.
[1]
A composition for reducing blood uric acid level, which contains Bifidobacterium breve as an active ingredient.
[2]
A composition for preventing or ameliorating hyperuricemia, which contains Bifidobacterium breve as an active ingredient.
[3]
The composition according to [1] or [2], wherein the Bifidobacterium breve is Bifidobacterium bleve MCC1274 (FERM BP-11175).
[4]
The composition according to any one of [1] to [3], which is a pharmaceutical composition.
[5]
The composition according to any one of [1] to [3], which is a food and drink composition.
[6]
The composition according to [4], which comprises 10 ⁶ to 10 ¹² cfu of Bifidobacterium breve MCC1274 (FERM BP-11175) per packaging unit.
[7]
The composition of [5], which comprises 10 ⁶ to 10 ¹² cfu of Bifidobacterium breve MCC1274 (FERM BP-11175) per serving.
[8]
The composition of [6] or [7], which is fermented milk.
[9]
Use of Bifidobacterium breve in blood uric acid level reducing agents, medicines for reducing blood uric acid level, or foods and drinks for reducing blood uric acid level.
[10]
Use of Bifidobacterium breve in foods and drinks for preventing or improving hyperuricemia, drugs for preventing or improving hyperuricemia, or foods and drinks for preventing or improving hyperuricemia.
[11]
The use of [9] or [10], wherein the Bifidobacterium breve is Bifidobacterium bleve MCC1274 (FERM BP-11175).
[12]
A method for reducing blood uric acid levels, which comprises administering Bifidobacterium breve to a subject.
[13]
A method for preventing or ameliorating hyperuricemia, which comprises administering Bifidobacterium breve to a subject.
[14]
The method of [12] or [13], wherein the Bifidobacterium breve is Bifidobacterium breve MCC1274 (FERM BP-11175).

Hereinafter, the present technology will be described in more detail based on Examples.
It should be noted that the examples described below show examples of typical examples of the present technology, and the scope of the present technology is not narrowly interpreted by this.

[Experimental Example 1]
<Manufacturing of test sample>
Fermented milk containing the Bifidobacterium Breve MCC1274 strain (FERM BP-11175) was produced by the following procedure.
First, dairy raw materials, water as needed, other components and the like were mixed, and homogenization treatment and heat sterilization treatment were carried out by a conventional method. The freeze-dried bacterial powder of Bifidobacterium Breve MCC1274 strain (FERM BP-11175) and a lactic acid bacterium starter are added (inoculated) to the heat-sterilized sterilized milk preparation liquid, and the mixture is fermented at a predetermined fermentation temperature to obtain pH. When the target value was reached, the formed curd was crushed by stirring and cooled to 10 ° C. or lower to produce fermented milk, which was used as a test sample.

<Subject>
Healthy subjects (BMI: 25 or more and less than 30) whose age at the time of obtaining consent was 20 to 65 years old were enrolled in the clinical trial. Furthermore, 70 persons who did not violate the following exclusion criteria (1) to (6) were selected as subjects by body composition measurement, blood test, and interview by a doctor. The average age of the subjects was 47.6 ± 8.6 years.
(1) Persons with a history of serious illnesses (2) Persons receiving drug treatment for lifestyle-related diseases (diabetes, hypertension, dyslipidemia) (3) Persons with drug allergies or serious food allergies Persons (4) Those who are pregnant, those who intend to become pregnant during the test period, those who are breastfeeding (5) Heavy smokers, heavy drinkers (6) Subject background, physical findings, interviews, etc. Or a person who is judged to be inappropriate as a subject by the test-sharing doctor

<Test method>
After a two-week pre-observation period, subjects ingested test samples once daily after meals for 12 consecutive weeks, morning, noon, and night. The viable cell count of the Bifidobacterium Breve MCC1274 strain (FERM BP-11175) contained in the test sample was 100 million or more per day (1). That is, the daily intake was set to 100 million or more as viable bacteria of Bifidobacterium Breve MCC1274 (FERM BP-11175).

Blood tests were performed on the subjects before ingestion (baseline: week 0) and at week 12, and the blood uric acid concentration (mg / dL) was measured. After the start of the test, one person was found to have stopped the test at his / her own will. In addition, those who did not meet the predetermined target criteria (that is, those who took less than 80% of the test sample, those who violated the taking of medicines or prohibited foods, and other serious test implementation plans It was decided to measure excluding those who were found to have violated or deviated), but in this test, none of the above was applicable. Therefore, the analysis was performed on 69 subjects who completed the test.

<Result>
The measurement results of blood uric acid levels at the 0th and 12th weeks are shown in Table 1 below.

The t-test showed a significant reduction in blood uric acid levels from baseline at week 12. Therefore, it was suggested that the blood uric acid level could be reduced or hyperuricemia could be prevented or ameliorated.

[Experimental Example 2]
<Manufacturing of test sample>
The culture solution of Bifidobacterium Breve MCC1274 (FERM BP-11175) was concentrated and then lyophilized to obtain a live lyophilized powder. This viable lyophilized powder was mixed with an excipient and filled in a capsule as a test sample.

<Subject>
Healthy subjects (BMI: 25 or more and less than 30) whose age at the time of obtaining consent was 20 to 65 years old were enrolled in the clinical trial. Furthermore, 40 persons who did not violate the following exclusion criteria (1) to (7) were selected as subjects by body composition measurement, blood test, and interview by a doctor. The average age of the subjects was 45.4 ± 9.8 years.
(1) Those who are being treated for serious diseases or those who have a serious history of these (2) Those who have gastrointestinal diseases and are taking medication (3) Lifestyle-related diseases (diabetes, Those who are receiving drug treatment (hypertension, dyslipidemia) (4) Those who have a history of drug allergy or serious food allergy (5) Those who are pregnant, those who intend to become pregnant during the study period, Those who are breastfeeding (6) Heavy smokers, heavy drinkers, people with irregular lifestyles (7) Based on the results of subject background, physical findings, interviews, etc., the investigator or the investigator judged that the subject was inappropriate. Person

<Test method>
After a 2-week pre-observation period, subjects ingested the test sample once daily with water or the like within 30 minutes after eating for 12 weeks. That is, the daily intake was set to 20 billion viable bacteria of Bifidobacterium Breve MCC1274 (FERM BP-11175).

Blood tests were performed on the subjects before ingestion (baseline: week 0) and at week 12, and the blood uric acid concentration (mg / dL) was measured. Those who did not meet the predetermined target criteria (that is, those who took less than 80% of the test sample, those who violated taking medicines or prohibited foods, and other important test implementation plans It was decided to measure excluding those who were found to have violated or deviated), but in this test, none of the above was applicable. Therefore, the analysis was performed on 40 subjects who completed the test.

<Result>
The measurement results of blood uric acid levels at the 0th and 12th weeks are shown in Table 2 below.

A t-test showed a significant reduction in blood uric acid levels from baseline at week 12. Therefore, it was suggested that the blood uric acid level could be reduced or hyperuricemia could be prevented or ameliorated.

[Manufacturing example]
The following are examples of production of pharmaceutical compositions for reducing blood uric acid levels or for preventing or improving hyperuricemia, and food and drink compositions.

[Manufacturing Example 1]
Bifidobacterium Breve MCC1274 (FERM BP-11175) was added to 3 mL of MRS liquid medium, and after anaerobic culture at 37 ° C. for 16 hours, the culture solution was concentrated, lyophilized, and lyophilized powder of bacteria (bacteria). Get the end). Bacterial powder, Whey protein concentrate (WPC), and prebiotics (lacturose, raffinose, and galactooligosaccharide) are uniformly mixed to obtain a composition. 20 g of the composition is dissolved in 200 g of water to obtain a composition for reducing blood uric acid level or a composition for preventing or improving hyperuricemia. Administration of these compositions can reduce blood uric acid levels or prevent or ameliorate hyperuricemia.

[Manufacturing Example 2]
Bifidobacterium Breve MCC1274 (FERM BP-11175) was added to 3 mL of MRS liquid medium, and after anaerobic culture at 37 ° C. for 16 hours, the culture solution was concentrated, lyophilized, and lyophilized powder of bacteria (bacteria). Get the end). Uniform powder of bacterial powder, dry powder of milk protein concentrate (MPC480, manufactured by Fontera, protein content 80% by mass, casein protein: whey protein = about 8: 2) and prebiotics (lacturose, raffinose and galactooligosaccharide) To obtain the composition. 20 g of the composition is dissolved in 200 g of water to obtain a composition for reducing blood uric acid level or a composition for preventing or improving hyperuricemia. Administration of these compositions can reduce blood uric acid levels or prevent or ameliorate hyperuricemia.

[Manufacturing Example 3]
Bifidobacterium Breve MCC1274 (FERM BP-11175) was added to 3 mL of MRS liquid medium, and after anaerobic culture at 37 ° C. for 16 hours, the culture solution was concentrated, lyophilized, and lyophilized powder of bacteria (bacteria). Get the end). Next, prebiotics (lacturose, raffinose, and galactooligosaccharides) and crystalline cellulose are put into a stirring granulator and mixed. Then, purified water is added to granulate and the granulated product is dried to obtain a granulated product (pharmaceutical composition) containing an extract component of bacteria and prebiotics and containing an excipient. By administration of the composition, the blood uric acid level can be reduced, or hyperuricemia can be prevented or ameliorated.

[Manufacturing Example 4]
The method for producing fermented milk to which Bifidobacterium Breve MCC1274 (FERM BP-11175) is added is shown below.

First, the dairy raw material, water if necessary, other components and the like are mixed, preferably homogenized, and heat sterilized. The homogenization treatment and the heat sterilization treatment can be carried out by a conventional method. A lactic acid bacterium starter is added (inoculated) to a heat-sterilized sterilized emulsion and fermented at a predetermined fermentation temperature to obtain a fermented product. Fermentation forms curds.

As the lactic acid bacterium starter, for example, lactic acid bacteria usually used for yogurt production such as Lactobacillus bulgaricus, Lactococcus lactis, and Streptococcus thermophilus can be used. When the pH reaches the target value, the formed curd is crushed by stirring and cooled to 10 ° C. or lower to obtain a fermented product. By cooling to 10 ° C. or lower, the activity of lactic acid bacteria can be reduced and the production of acid can be suppressed.

Next, the fermented product obtained in the fermentation step is heat-treated to obtain a fermented product after heating (fermented product after heat treatment). By appropriately heating the fermented product, it is possible to suppress the production of acid by lactic acid bacteria in the fermented product after heating. As a result, it is possible to suppress a decrease in pH during the subsequent production process and / or during storage of the concentrated fermented milk containing bifidobacteria, and as a result, the survivability of bifidobacteria can be improved.

Bifidobacterium breve MCC1274 (FERM BP-11175) and prebiotics (lacturose, raffinose, and galactooligosaccharides) are then added to the post-heated fermented product obtained in the heat treatment step. The amount of Bifidobacterium Breve MCC1274 (FERM BP-11175) added is preferably 1 × 10 ⁷ to 1 × 10 ¹¹ cfu / ml with respect to the fermented product after heating, and 1 × 10 ⁸ to 1 × 10 ¹⁰ cfu. / Ml is more preferred. If Bifidobacterium Breve MCC1274 (FERM BP-11175) is dead, cfu / mL can be replaced with individual cells / mL.

After heating, the fermented product is added with Bifidobacterium Breve MCC1274 (FERM BP-11175) and prebiotics, and then concentrated. The concentration step can be carried out by appropriately using a known concentration method. For example, a centrifugation method or a membrane separation method can be used. In the centrifugation method, whey in the concentrate (bifidobacterium and fermented product after heating to which prebiotics are added) is removed to increase the solid content concentration of bifidobacteria and concentrated fermented milk containing prebiotics. Is obtained.

By administering the fermented milk obtained as described above, the blood uric acid level can be reduced, or hyperuricemia can be prevented or ameliorated.

[Manufacturing Example 5]
The method for producing the prepared milk powder to which Bifidobacterium Breve MCC1274 (FERM BP-11175) is added is shown below.

Desalted milk whey protein powder (manufactured by Mirai) 10 kg, milk casein powder (manufactured by Fontera) 6 kg, lactose (manufactured by Mirai) 48 kg, mineral mixture (manufactured by Tomita Pharmaceutical Co., Ltd.) 920 g, and vitamin mixture (manufactured by Tanabe Pharmaceutical Co., Ltd.) ) 32 g, lactose (manufactured by Morinaga Dairy Co., Ltd.) 500 g, raffinose (manufactured by Nippon Jinna Sugar Co., Ltd.) 500 g, galactooligosaccharide liquid sugar (manufactured by Yakult Pharmaceutical Co., Ltd.) 900 g, dissolved in warm water 300 kg, and further heated and dissolved at 90 ° C. for 10 minutes. , 28 kg of prepared fat (manufactured by Taiyo Yushi Co., Ltd.) was added and homogenized. Then, the steps of sterilization and concentration were performed, and the mixture was spray-dried to prepare about 95 kg of prepared milk powder. To this, 100 g of bacterial cell powder (1.8 × 10 ¹¹ cfu / g, manufactured by Morinaga Milk Industry Co., Ltd.) of Bifidobacterium Breve MCC1274 (FERM BP-11175) doubled in starch was added, and Bifidobacterium oligo Prepare about 95 kg of sugar-blended milk powder. The resulting formula milk is dissolved in water, the total solids concentration of 14% with a standard milk formula Concentration (w / v) when the tone emulsions, tone number of bifidobacteria in the emulsion is 2.7 × 10 ⁹ cfu / 100 mL can be obtained.

By administering the adjusted milk powder obtained as described above, the blood uric acid level can be reduced, or hyperuricemia can be prevented or ameliorated.

Claims (5)

A composition for reducing blood uric acid level, which contains Bifidobacterium breve as an active ingredient. A composition for preventing or ameliorating hyperuricemia, which comprises Bifidobacterium breve as an active ingredient. The composition according to claim 1 or 2, wherein the Bifidobacterium breve is Bifidobacterium bleve MCC1274 (FERM BP-11175). The composition according to any one of claims 1 to 3, which is a pharmaceutical composition. The composition according to any one of claims 1 to 3, which is a food and drink composition.