JP7309436B2 - A composition for preventing or improving renal dysfunction, and pharmaceutical compositions and food and drink compositions using the composition for preventing or improving renal dysfunction - Google Patents

Description

IPOD FERM BP-11175

Application of Article 30, Paragraph 2 of the Patent Law Bioscience of Microbiota, Food and Health Vol. 37(3), 67-75, 2018 Released May 8, 2018

The present technology relates to a composition for preventing or improving renal dysfunction, and pharmaceutical compositions and food and drink compositions using the composition for preventing or improving renal dysfunction.

Kidney disease, except for acute nephritis, is a disease that lasts a lifetime, and may eventually lead to end-stage renal failure (a condition that requires dialysis therapy). Because the kidneys have considerable reserve capacity, chronic renal failure is mostly asymptomatic until its function drops below 20%. In other words, when symptoms appear, there is a high possibility of end-stage renal failure, and in many cases the symptoms have progressed to the stage where dialysis is required.

Currently, the number of chronic dialysis patients is about 200,000, and it is said that 30,000 or more new dialysis patients are introduced every year. For Chronic Kidney Disease (CKD), the goal is to delay the progress of the disease and prolong the renal function as long as possible, and there is no cure for the disease itself. Currently, dietary therapy and drug therapy for renal failure suppress the progression of the disease and prolong the remaining function of the kidneys.

Under such circumstances, conventionally, there has been a demand for the development of drugs and compositions that are effective in preventing or improving renal dysfunction. On the other hand, for example, Patent Document 1 discloses a renal function improving agent comprising a specific synthetic compound. Also, US Pat. No. 6,200,003 discloses compositions for increasing kidney function that reduce creatinine and BUN levels in a subject, comprising certain types of probiotic bacteria.

Japanese Patent Publication No. 2011-509941 JP 2013-209396 A

As described above, conventionally, various proposals have been made for methods of preventing and treating renal dysfunction. However, as in Patent Document 1, the method using a synthetic compound or the like raises concerns about side effects. In addition, as in Patent Document 2, several methods for preventing or treating renal dysfunction by ingesting probiotic cells or fermentation products have already been reported, but probiotics differ from strain to strain. It is known to exhibit physiological effects, and inconsistent results have not been obtained.

Therefore, the main object of the present technology is to provide a novel composition for preventing or improving renal dysfunction.

That is, in the present technology, first, Bifidobacterium breve is used as an active ingredient , and the Bifidobacterium breve is Bifidobacterium breve MCC1274 (FERM BP-11175), renal dysfunction prevention or A remedy composition is provided .
The composition may also improve glomerular function.
Further, the composition may reduce blood creatinine levels.
In addition, the composition can be used as a pharmaceutical composition or a food or drink composition.

According to the present technology, a new composition for preventing or improving renal dysfunction can be provided.
Note that the effects described here are not necessarily limited, and may be any of the effects described in this specification.

Preferred embodiments for implementing the present technology are described below.
It should be noted that the embodiments described below are examples of representative embodiments of the present technology, and the scope of the present technology should not be construed narrowly.

1. Composition for Preventing or Improving Renal Dysfunction A composition for preventing or ameliorating renal dysfunction of the present technology is characterized by containing Bifidobacterium breve as an active ingredient.

Bifidobacterium breve is one of the fungal species belonging to the genus Bifidobacterium. Bifidobacterium breve lives mainly in the large intestine of infants, and among the species belonging to the genus Bifidobacterium, Bifidobacterium longum subsp. ), etc., are known as infant-type Bifidobacterium bacteria.

The composition for preventing or improving renal dysfunction of the present technology has excellent safety and long-term continuous It is very useful because there is little need to worry about side effects even if it is administered in a targeted manner. Furthermore, it is highly safe even when used in combination with other drugs.

Examples of bacteria belonging to Bifidobacterium breve include Bifidobacterium breve 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, and the like. ) is preferably used.

MCC1274 is an independent administrative agency National Institute of Advanced Industrial Science and Technology Patent Organism Depositary Center (Japan 〒 305-8566 1-1-1 Higashi Tsukuba City, Ibaraki Prefecture Central 6 (currently IPOD Independent Administrative Agency Product Evaluation Technology Institute Patent Organism Depositary Center ( NITE-IPOD): Japan, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture 292-0818, Room 120), since August 25, 2009, has been deposited under the deposit number IPOD FERM BP-11175.

In addition, the strains specified by the strain names exemplified above are not limited to strains themselves that have been deposited or registered with a predetermined institution under the strain name (hereinafter, for convenience of explanation, also referred to as "deposited strain"). Strains substantially equivalent thereto (also referred to as "derivative strains" or "derived strains") are also included. That is, for example, "Bifidobacterium breve MCC1274 (FERM BP-11175)" is not limited to the strain itself deposited with the depositary institution under the deposit number of MCC1274 (FERM BP-11175), and substantially Also included are strains equivalent to . Regarding strains, the term "substantially equivalent to the above-deposited strain" refers to a strain that belongs to the same species as the above-deposited strain and that is capable of preventing or improving renal dysfunction, which is the effect of the present technology. A strain substantially equivalent to the above deposited strain may be, for example, a derivative strain having the deposited strain as a parent strain. Derivative strains include strains bred from the deposited strain and strains that arise naturally from the deposited strain.

Substantially identical strains and derivative strains include, for example, the following strains.
(1) Strains determined to be the same strain by the RAPD (Randomly Amplified Polymorphic DNA) and PFGE (Pulsed-field gel electrophoresis) methods (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, has no foreign genes, and has a DNA identity of 95% or more (3) A strain bred from the strain (genetic engineering modification, mutation , including spontaneous mutations), strains with identical traits

In the present technology, "renal dysfunction" includes various renal diseases related to renal dysfunction, and is caused by acute nephritis or chronic nephritis, diabetes, gout, side effects of drugs, etc., renal filtration Indicates a state with symptoms such as decreased function and abnormal circulation in the body. Such renal diseases include, for example, various glomerular diseases (acute nephritic syndrome, rapidly progressive nephritic syndrome, recurrent (recurrent)/persistent hematuria, chronic nephritic syndrome, nephrotic syndrome, hereditary nephropathy (nephropathy) , diffuse glomerulonephritis, dense deposit disease, etc.), renal tubulointerstitial disease, renal failure, kidney stones/urinary tract stones, etc. In the morphological classification of glomerular diseases, for example, primary Glomerular disease (minimal change, focal glomerulosclerosis, membranous nephropathy, mesangial proliferative glomerulonephritis (IgA nephropathy, non-IgA nephropathy), membranous proliferative glomerulonephritis, diffuse sclerosing thread) Spheronephritis, etc.), and renal diseases based on systemic diseases include collagen disease kidney (scleroderma nephritis, lupus nephritis, etc.), diabetic nephropathy, renal amyloidosis, purpura nephritis, renal gout, hereditary renal disease (hereditary nephritis, Alport syndrome, Fabry disease, etc.) and the like. The composition for preventing or improving renal dysfunction of the present technology is used for preventing or improving primary and secondary renal diseases including these renal diseases (including glomerular lesions in transplanted kidneys). be able to.

In the present technology, renal dysfunction can be evaluated by blood creatinine level (sometimes referred to as "serum creatinine level"), blood urea nitrogen (BUN), creatinine clearance, and the like. Renal function can also be evaluated by estimated glomerular filtration rate (eGFR) calculated from sex, age, and blood creatinine level.

In the present technology, "amelioration" refers to amelioration of a disease, symptom or condition; prevention or delay of worsening of a disease, symptom or condition; reversal, prevention or delay of progression of a disease or condition. In addition, "prevention" refers to preventing or delaying the onset of a disease or symptom in an application subject, or reducing the risk of a disease or symptom in an application subject.

Specific symptoms of renal dysfunction include, in particular, decreased glomerular function and increased blood creatinine level. Glomeruli play a central role in renal function, and glomerular filtration rate (GFR), which indicates the function of glomeruli, is known to be an index that reflects renal function. When GFR is decreased due to decreased glomerular function, sufficient excretion of metabolites and the like becomes impossible. In addition, creatinine is a waste product of protein contained in muscles, and is originally filtered by the glomerulus of the kidney and excreted in the urine. decreases and creatinine builds up in the blood. Therefore, it is known that blood creatinine levels increase as renal function declines. The composition for preventing or ameliorating renal dysfunction of the present technology has an effect on a decrease in glomerular function and a decrease in blood creatinine level. It has an effect on decreasing values.

The subject of the composition for preventing or improving renal dysfunction 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. In addition, because of its high safety, the composition for preventing or improving renal dysfunction of the present technology can be It can also be used for sick people.

The composition for preventing or improving renal dysfunction of the present technology includes Bifidobacterium breve MCC1274 (FERM BP-11175) as its active ingredient, Bifidobacterium breve MCC1274 (FERM BP-11175). may contain objects.

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

As a carbon source, for example, sugars such as glucose, galactose, lactose, arabinose, mannose, sucrose, starch, starch hydrolysates, blackstrap molasses, etc. can be used depending on their assimilation. As the nitrogen source, for example, ammonia, ammonium salts such as ammonium sulfate, ammonium chloride and ammonium nitrate, and nitrates can be used. Examples of inorganic salts that can be used include sodium chloride, potassium chloride, potassium phosphate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, and ferrous sulfate. Organic ingredients such as peptone, soybean flour, defatted soybean meal, meat extract and yeast extract may also be used.

Cultivation conditions are not particularly limited as long as they do not impair the effects of the present technology, but for example, the culture temperature is usually 25 to 50°C, preferably 35 to 42°C. In addition, the culture is preferably performed under anaerobic conditions, and for example, the culture can be performed while aerating an anaerobic gas such as carbon dioxide gas. Moreover, you may culture|cultivate under microaerophilic conditions, such as liquid stationary culture.

After culturing, the Bifidobacterium breve used in the present technology may be used as it is, or diluted or concentrated, or the cells collected from the culture may be used. . The term "culture" as used herein is a concept that also includes culture supernatant.

After culturing, the culture obtained may be used as it is, or may be used after being 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, the present fungus body 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. Killed bacteria include dead bacteria sterilized by heating, freeze-drying, or the like. Other methods for preparing dead cells include spray drying, retort sterilization, freeze drying, UHT sterilization, autoclave sterilization, high-pressure steam sterilization, dry heat sterilization, and distribution steam sterilization. , electromagnetic wave sterilization, electron beam sterilization, high frequency sterilization, radiation sterilization, ultraviolet sterilization, ethylene oxide gas sterilization, hydrogen peroxide gas plasma sterilization, chemical sterilization (alcohol sterilization, formalin fixation, electrolysis) water treatment method) and the like. Further, the present fungus body may be a crushed product. The crushed product may be obtained by crushing live bacteria or crushing dead bacteria, or may be subjected to heating, freeze-drying, or the like after crushing. In addition, crushing can be selected using methods and equipment known in the art, such as physical crushing, enzymatic dissolution treatment, chemical treatment, autolysis treatment, and the like.

Physical crushing may be performed in the state of cell suspension or in the state of 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., and filter filtration. Disruption by damaging the cells can be selected. As the enzymatic lysis treatment, for example, an enzyme such as lysozyme can be used to destroy the cell structure of the fungus. As the chemical treatment, for example, surfactants such as soybean phospholipids and glycerol fatty acid esters can be used to destroy the cell structure of the cells. As the autolysis treatment, for example, the cells can be dissolved by the enzymes of some of the lactic acid bacteria themselves. Physical disruption is preferred in this technique because it does not require the addition of other chemicals or compounds.

The composition for preventing or improving renal dysfunction according to the present technology may consist of only the active ingredient, or may be a composition containing the active ingredient and optional ingredients other than the active ingredient. The optional component is not particularly limited as long as it does not impair the effect of the present technology, and additives conventionally blended in pharmaceuticals (for example, formulation carriers described later) can be blended.

2. Specific Forms of Composition for Preventing or Improving Renal Dysfunction According to the Present Technology The composition for preventing or improving renal dysfunction according to the present technology can be used in various forms such as food and drink, pharmaceuticals, quasi-drugs, and feed. can.

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 treatment, that is, treatment of the human body by treatment, and includes, for example, health promotion and beauty treatment.

<Food and drink>
Food and drink compositions using the composition for preventing or improving renal dysfunction of the present technology (hereinafter also simply referred to as "food and drink compositions of the present technology") can be prepared by adding them to known food and drink. It is also possible to produce a new food or drink by mixing it with the raw material of the food or drink.

The food and drink composition of the present technology can be in any form such as liquid, paste, solid, powder, etc. In addition to tablets, liquid foods, etc., for example, flour products, instant foods, processed agricultural products, processed marine products, livestock Examples include processed products, milk/dairy products, oils and fats, basic seasonings, compound seasonings/foods, frozen foods, confectionery, beverages, and other commercially available products.

Wheat flour products include, for example, bread, macaroni, spaghetti, noodles, cake mixes, fried chicken flour, and bread crumbs.
Examples of instant foods include instant noodles, cup noodles, retort/cooked foods, cooked canned foods, microwave oven foods, instant soups/stews, instant miso soups/soup, 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, and cereals (processed grain products).
Examples of processed marine products include canned marine products, fish hams and sausages, fish paste products, marine delicacies, boiled fish cakes, and the like.
Examples of processed livestock products include canned livestock products, pastes, livestock hams, sausages, and the like.
Examples of milk and dairy products include fermented milk such as yoghurt, processed milk, milk drinks, lactic acid beverages, cheese, ice creams, formulated milk powders, cream, modified milk powder for infants, nutritional supplements for infants, and pregnant women.・Mother's milk for lactating women and other dairy products.
Fats and oils include, for example, butter, margarines, and vegetable oils.
Basic seasonings include, for example, soy sauce, miso, sauces, processed tomato seasonings, mirin, and vinegars. Examples include dressings, noodle soups, spices, and other compound seasonings.
Frozen food includes, for example, material frozen food, half-cooked frozen food, cooked frozen food, and the like.
Confectionery includes, for example, caramels, candies, chewing gums, chocolates, cookies, biscuits, cakes, pies, snacks, crackers, Japanese confections, rice confections, bean confections, dessert confections, and other confectionery.
Examples of beverages include carbonated drinks, natural fruit juices, fruit juice drinks, soft drinks containing fruit juice, pulp drinks, fruit drinks containing fruit, vegetable drinks, soy milk, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, Examples include sports drinks, nutritional drinks, alcoholic drinks, and other beverages of choice.
Examples of commercially available foods other than these include baby food, furikake (sprinkle), and ochazuke nori.

The food and drink composition of the present technology can be produced by adding the present fungus to raw materials of ordinary food and drink, and is produced in the same manner as ordinary food and drink except for adding the present fungus. be able to. Addition of the present fungus may be performed at any stage of the manufacturing process of the food and drink composition. Moreover, a food and drink composition may be produced through a fermentation step using the added fungus. Examples of such food and drink compositions include lactic acid bacteria beverages, fermented milk and the like.

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

In addition, for example, it is possible to adopt a method of adding the present fungus to expressed breast milk and ingesting it orally, or a method of ingesting it through a nasogastric feeding tube or the like for newborns and infants.

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 that assists the probiotic effect may be used. can be done.

Specifically, for example, various proteins such as whey protein, casein protein, soy protein, or pea protein (pea protein), mixtures thereof, degradation products; amino acids such as leucine, valine, isoleucine or glutamine; vitamin B6 or vitamins vitamins such as C; creatine; citric acid; fish oil; It can be manufactured by blending with the present bacterial cells.

Examples of human milk oligosaccharides include 2'-fucosyllactose, 3-fucosyllactose, 2',3-difucosyllactose, lacto-N-triose II, lacto-N-tetraose, lacto-N-neotetraose, Lacto-N-fucopentaose I, lacto-N-neofucopentaose, lacto-N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-fucopentaose V, lacto-N-neofucopentaose V, lacto-N -Neutral human milk oligosaccharides such as Difcohexaose I, Lacto-N-Difcohexaose II, 6'-galactosyl lactose, 3'-galactosyl lactose, lacto-N-hexaose and lacto-N-neohexaose , 3′-sialyllactose, 6′-sialyllactose, 3-fucosyl-3′-sialyllactose, disialyl-lacto-N-tetraose, and other acidic human milk oligosaccharides.

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 and drink composition is 1×10 ³ to 1×10 ¹² with respect to the final composition of the food and drink composition. It is more preferable to contain cfu/g. In addition, the daily dosage is at least 1×10 ³ cfu/day or more, 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 at least cfu/day or more. In the present technology, it is particularly preferable to include 10 ⁶ to 10 ¹² cfu of Bifidobacterium breve MCC1274 (FERM BP-11175) per serving. In addition, "cfu" represents a colony forming unit. When the bacterial cells are dead cells, cfu/g or cfu/ml can be replaced with individual cells/g or individual cells/ml. When the present fungus is a crushed product, it is possible to display the number of bacteria before crushing (individual cells/g) in terms of weight.

[Foods for special dietary uses]
The composition can be applied to foods with health claims and foods for special purposes. The Foods with Health Claims system was established to cover not only ordinary foods but also foods in the form of tablets, capsules, etc., based on domestic and international trends and consistency with the existing Foods for Specified Health Uses system. There are three types: food for specified health use, food with function claims, and food with nutrient function claims. Foods for special dietary uses are foods intended for special purposes for sick people, infants, the elderly, and other people who cannot eat regular meals. type), powdered milk for pregnant and lactating women, formula for infants, and food for people with difficulty swallowing.

Although not limited to the following description, the composition may be applied, for example, to a low-protein food for those with reduced renal function or an individually evaluated food for sick people, or to healthy people, It can be applied to foods with function claims for persons with renal function index in the normal high range or mild range.

Further, the food and drink composition of the present technology may include powdered milk for infants. "Infant formula" means infant formula intended for infants aged 0-12 months, follow-up formula intended for infants aged 6-9 months and younger and young children (up to 3 years of age), birth Low birth weight formula for infants weighing less than 2500 g at birth (low birth weight infants), various therapeutic formulas used to treat infants with morbid conditions such as cow's milk allergy and lactose intolerance etc.

Food and drink compositions of this technology include nutrition-adjusted foods such as milk for mothers during pregnancy and lactation (prepared milk containing well-balanced nutrition necessary for pregnancy and lactation), reconstituted milk for adults, Dietary supplements, nutritionally functional foods such as liquid diets, and foods for sick people (foods for special dietary uses) such as phosphorus-reduced powdered milk can be mentioned.

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

That is, in the present technology, powdered milk for infants or mothers is obtained by mixing powdered bacteria containing bacteria of the genus Bifidobacterium with prebiotics and/or powdered milk to obtain powdered milk for preventing or improving renal dysfunction. To provide a method for producing milk for infants.

Specifically, for example, a method for producing powdered milk for enhancing breast milk components is provided, comprising the following steps (A) to (C):
(A) culturing bacteria of the genus Bifidobacterium in a medium containing milk components to obtain a culture;
(B) subjecting the culture to spray-drying and/or freeze-drying to obtain a bacterial powder;
(C) A step of mixing the bacterial cell powder with prebiotics and/or powdered milk to obtain powdered milk for preventing or improving renal dysfunction.

〔supplement〕
Further, the food and drink composition of the present technology may be a supplement for preventing or improving renal dysfunction.

A supplement for preventing or improving renal dysfunction can be produced, for example, by the following method.

That is, the present technology provides, for example, a method for producing a supplement for preventing or improving renal dysfunction, including the following steps (A) and (B):
(A) mixing prebiotics, Bifidobacterium bacteria, and excipients to obtain a mixture;
(B) a step of tableting the mixture;

[Food and drink with functional claims]
In addition, the food and drink composition defined by the present technology can be provided and sold as a food and drink labeled with specific uses (especially health uses) and functions.

The act of "indication" includes all acts to inform consumers of the above-mentioned use. Regardless of the object, medium, etc. to be displayed, all fall under the "display" act of this technology.

In addition, it is preferable that the "display" be performed in an expression that allows the consumer to directly recognize the use. Specifically, the act of transferring, handing over, displaying for the purpose of transfer or delivery, importing products related to food and beverages or product packaging that describes the above-mentioned use, advertisements related to products, price lists or transaction documents Examples include the act of displaying or distributing information with the above-mentioned use described, or providing information containing such information with the above-mentioned use by electromagnetic means (Internet, etc.).

On the other hand, the content of the display is preferably a display approved by the government (for example, a display that is approved 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, POP and other advertising materials at sales sites, other documents, and the like.

In addition, "labeling" includes health food, functional food, food for the sick, enteral nutritional food, food for special dietary uses, food with health claims, food for specified health use, food with function claims, food with nutrient function claims, and medical products. Display as an off-the-shelf item is also possible. Among these, in particular, the labeling approved by the Consumer Affairs Agency, for example, the labeling approved by the Foods for Specified Health Uses system, the Foods with Function Claims system, and systems similar thereto can be mentioned. More specifically, labeling as food for specified health use, labeling as food for specified health use with certain conditions, labeling as food with function claims, labeling to the effect that it affects the structure and function of the body, labeling to reduce disease risk, etc. can be mentioned. Among them, a typical example is labeling as a food for specified health use (especially labeling of health use) stipulated in the Health Promotion Law Enforcement Regulations (Ministry of Health, Labor and Welfare Ordinance No. 86 of April 30, 2003). , Labeling as food with function claims stipulated in the Food Labeling Law (Law No. 70 of 2013) and similar labeling.

In addition, the wording used for labeling as described above is not only words such as renal dysfunction prevention or improvement, but also other words such as various diseases related to renal dysfunction prevention or improvement. Needless to say, any wording that expresses the effect of prevention, treatment and/or improvement of symptoms is included within the scope of the present technology. Examples of such phrases include, for example, "For those concerned about renal function" and "For those concerned about blood creatine levels." Display based on usage is also possible. It is also possible to display renal dysfunction prevention or improvement effects based on results evaluated using new renal function markers such as cystatin C and renal function measurement methods.

<Pharmaceuticals and quasi-drugs>
A pharmaceutical composition or a quasi-drug composition using the composition for preventing or improving renal dysfunction of the present technology (hereinafter also simply referred to as “the pharmaceutical composition of the present technology”) is a known pharmaceutical or quasi-drug It can be prepared by adding it to a product (hereinafter also referred to as "pharmaceuticals, etc."), or it can be mixed in the raw materials of pharmaceuticals, etc. to produce new pharmaceuticals, etc.

When the composition for preventing or improving renal dysfunction of the present technology is used in a composition such as a pharmaceutical composition, the composition should be appropriately formulated into a desired dosage form according to the administration method such as oral administration or parenteral administration. can be done. The dosage form is not particularly limited, but in the case of oral administration, for example, solid preparations such as powders, granules, tablets, troches, and capsules; liquid preparations such as solutions, syrups, suspensions, emulsions, etc. can be For parenteral administration, it can be formulated into, for example, suppositories, sprays, inhalants, ointments, patches, injections, and the like. In the present technology, it is preferred to formulate into a dosage form for oral administration. In addition, formulation can be suitably implemented by a well-known method according to a dosage form.

At the time of formulation, it may be formulated by appropriately blending formulation carriers. Further, in addition to the composition for preventing or improving renal dysfunction of the present technology, ingredients such as excipients, pH adjusters, colorants, and corrigents that are usually used for formulation can be used. Furthermore, it is also possible to use ingredients having effects of prevention, amelioration and/or treatment of diseases or symptoms that are known or to be discovered in the future, depending on the purpose, as long as the effect of the present technology is not impaired.

Various organic or inorganic carriers can be used as pharmaceutical carriers depending on the dosage form. Examples of carriers for solid preparations include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents and the like.

Excipients include, for example, sugar derivatives such as lactose, sucrose, glucose, mannitol, sorbitol; starch derivatives such as corn starch, potato starch, α-starch, dextrin, carboxymethyl starch; crystalline cellulose, hydroxypropyl cellulose, Hydroxypropylmethylcellulose, carboxymethylcellulose, cellulose derivatives such as carboxymethylcellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light silicic anhydride, synthetic aluminum silicate, and magnesium aluminometasilicate; phosphate derivatives such as calcium phosphate; carbonate derivatives such as calcium; sulfate derivatives such as calcium sulfate;

Examples of binding agents include gelatin, polyvinylpyrrolidone, macrogol, etc., in addition to the excipients described above.

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

Lubricants include, for example, talc; stearic acid; metal stearates such as calcium stearate and magnesium stearate; colloidal silica; waxes such as pea gum and gairou; ; carboxylic acid sodium salts such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acid anhydride and silicic acid hydrate; be done.

Examples of stabilizers include paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; acetic anhydride;

Flavoring agents include, for example, sweeteners, acidulants, flavoring agents, and the like.

In the case of liquid preparations for oral administration, carriers used include solvents such as water, flavoring agents, 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 this technology, in particular, the content of Bifidobacterium breve MCC1274 (FERM BP-11175) in the pharmaceutical composition is 1×10 ³ to 1×10 ¹² with respect to the final composition of the pharmaceutical composition. It is more preferable to contain cfu/g. In addition, the daily dosage is at least 1×10 ³ cfu/day or more, more preferably 1×10 ⁶ cfu/day or more, more preferably 1×10 ⁸ cfu/day or more, more preferably 2×10 ¹⁰ cfu/day or more, or preferably more. In the present technology, it is particularly preferable to include 10 ⁶ to 10 ¹² cfu of Bifidobacterium breve MCC1274 (FERM BP-11175) per package.

<Feed>
A feed using the composition for preventing or improving renal dysfunction of the present technology can be prepared by adding it to a known feed, or can be mixed into raw materials of a feed to produce a new feed.

When the composition for preventing or improving renal dysfunction of the present technology is used as a feed, raw materials for the feed include, for example, cereals such as corn, wheat, barley, and rye; brans such as bran, wheat bran, rice bran, and defatted rice bran. Manufacture lees such as corn gluten meal and corn jam meal; Animal feeds such as skimmed milk powder, whey, fish meal, and bone meal; Yeasts such as brewer's yeast; Mineral feeds such as calcium phosphate and calcium carbonate; and saccharides. Examples of the form of feed include pet feed (pet food, etc.), livestock feed, fish feed, and the like.

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

The present technology can also employ the following configuration.
[1]
A composition for preventing or improving renal dysfunction, comprising Bifidobacterium breve as an active ingredient.
[2]
The composition of [1], wherein the Bifidobacterium breve is Bifidobacterium breve MCC1274 (FERM BP-11175).
[3]
The composition of [1] or [2], which improves glomerular function.
[4]
The composition according to any one of [1] to [3], which reduces blood creatinine levels.
[5]
The composition according to any one of [1] to [4], which is a pharmaceutical composition.
[6]
The composition according to any one of [1] to [4], which is a food or drink composition.
[7]
The composition according to [5], which contains 10 ⁶ to 10 ¹² cfu of Bifidobacterium breve MCC1274 (FERM BP-11175) per packaging unit.
[8]
The composition of [6], comprising 10 ⁶ to 10 ¹² cfu of Bifidobacterium breve MCC1274 (FERM BP-11175) per serving.
[9]
The composition of [7] or [8], which is fermented milk.
[10]
Use of Bifidobacterium breve in an agent for preventing or improving renal dysfunction, a pharmaceutical for preventing or improving renal dysfunction, or a food or drink for preventing or improving renal dysfunction.
[11]
The use of [10], wherein said Bifidobacterium breve is Bifidobacterium breve MCC1274 (FERM BP-11175).
[12]
A method for preventing or improving renal dysfunction, comprising administering Bifidobacterium breve to a subject.
[13]
The method of [12], wherein the Bifidobacterium breve is Bifidobacterium breve MCC1274 (FERM BP-11175).

Hereinafter, the present technology will be described in further detail based on examples.
It should be noted that the embodiments described below are examples of representative embodiments of the present technology, and the scope of the present technology should not be interpreted narrowly.

[Experimental example 1]
<Production of test sample>
Fermented milk containing Bifidobacterium breve MCC1274 strain (FERM BP-11175) was produced by the following procedure.
First, milk raw materials, water if necessary, other ingredients, etc. were mixed, and homogenization and heat sterilization were performed by a conventional method. Bifidobacterium breve MCC1274 strain (FERM BP-11175) freeze-dried bacterial powder and lactic acid bacteria starter are added (inoculated) to the heat-sterilized sterilized emulsion, and fermented at a predetermined fermentation temperature. When the target value was reached, the formed curd was crushed by stirring and cooled to 10°C or less to produce fermented milk, which was used as a test sample.

<Subject>
Healthy subjects aged 20 to 65 (BMI: 25 to 30) at the time of informed consent were enrolled in the clinical trial as subjects. Furthermore, 70 subjects who did not meet 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 subjects was 47.6±8.6 years.
(1) Those who have a history of serious diseases, etc. (2) Those who are undergoing drug treatment for lifestyle-related diseases (diabetes, hypertension, dyslipidemia) (3) Those who have drug allergies or severe food allergies (4) Those who are pregnant, those who intend to become pregnant during the study period, and those who are breast-feeding (5) Heavy smokers, heavy drinkers (6) From the results of subject background, physical findings, interviews, etc. Or those who are judged to be unsuitable as subjects by the investigator

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

Before the intake (baseline: 0th week) and at the 12th week, the subjects were subjected to a blood test to measure the blood creatinine concentration (mg/dL). After the start of the study, one subject discontinued the study voluntarily. In addition, those who did not meet the pre-specified inclusion criteria (i.e., those who consumed less than 80% of the study material, those who violated drug intake or prohibited foods, and other serious study protocol However, there were no such persons in this study. Therefore, the analysis was performed on 69 subjects who completed the study.

<Results>
Table 1 below shows the measurement results of blood creatinine levels at 0 and 12 weeks.

A significant decrease in blood creatinine levels from baseline was observed at week 12 by t-test. Therefore, it was suggested that renal dysfunction is prevented or improved.

[Experimental example 2]
<Production of test sample>
After concentrating the culture solution of Bifidobacterium breve MCC1274 (FERM BP-11175), it was lyophilized to obtain a live lyophilized powder. This freeze-dried powder of viable bacteria was mixed with excipients and filled into capsules to prepare test samples.

<Subject>
Healthy subjects aged 20 to 65 (BMI: 25 to 30) at the time of informed consent were enrolled in the clinical trial as subjects. Furthermore, 40 subjects who did not meet the following exclusion criteria (1) to (7) were selected by body composition measurement, blood test, and medical interview by a doctor, and used as subjects. The average age of subjects was 45.4±9.8 years.
(1) Those who are undergoing treatment for serious diseases, etc., or those who have a serious history of these (2) Those who suffer from gastrointestinal diseases and are taking medication (3) Lifestyle-related diseases (diabetes, (4) Subjects with a history of drug allergy or serious food allergy (5) Subjects who are pregnant or intend to become pregnant during the test period, (6) Subjects who are heavy smokers, heavy drinkers, and subjects with irregular lifestyles. who was

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

Before the intake (baseline: 0th week) and at the 12th week, the subjects were subjected to a blood test to measure the blood creatinine concentration (mg/dL). In addition, those who did not meet the predetermined inclusion criteria (i.e., those who ingested less than 80% of the test sample, those who violated the intake of pharmaceuticals or prohibited foods, and other serious study protocol However, there were no such persons in this study. Therefore, the analysis was performed on 40 subjects who completed the study.

<Results>
Table 2 below shows the measurement results of blood creatinine levels at 0 and 12 weeks.

At the 12th week, a downward trend was observed in the blood creatinine level from the baseline. Therefore, it was suggested that renal dysfunction is prevented or improved.

[Manufacturing example]
Production examples of pharmaceutical compositions and food compositions for preventing or improving renal dysfunction are shown below.

[Production 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 and lyophilized to obtain freeze-dried powder of bacteria (bacteria end). A composition is obtained by uniformly mixing bacterial powder, whey protein concentrate (WPC), and prebiotics (lactulose, raffinose and galacto-oligosaccharides). 20 g of the composition is dissolved in 200 g of water to obtain a composition for preventing or improving renal dysfunction. Administration of the composition can prevent or improve renal dysfunction.

[Production 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 and lyophilized to obtain freeze-dried powder of bacteria (bacteria end). Bacterial powder, dry powder of milk protein concentrate (MPC480, manufactured by Fonterra, protein content 80% by mass, casein protein: whey protein = about 8:2), and prebiotics (lactulose, raffinose and galacto-oligosaccharides) are uniformly mixed. to obtain a composition. 20 g of the composition is dissolved in 200 g of water to obtain a composition for preventing or improving renal dysfunction. Administration of the composition can prevent or improve renal dysfunction.

[Production 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 and lyophilized to obtain freeze-dried powder of bacteria (bacteria end). Next, prebiotics (lactulose, raffinose, and galacto-oligosaccharides) and crystalline cellulose are added to an agitating granulator and mixed. After that, purified water is added and the granules are dried to obtain granules (pharmaceutical composition) containing bacterial extracts and prebiotics and excipients. By administering the granules, renal dysfunction can be prevented or improved.

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

First, milk raw materials, optionally water, and other ingredients are mixed, preferably homogenized, and heat sterilized. Homogenization treatment and heat sterilization treatment can be performed by a conventional method. A lactic acid bacteria starter is added (inoculated) to the sterilized emulsion liquid that has been sterilized by heating, and the mixture is fermented at a predetermined fermentation temperature to obtain a fermented product. Curd is formed by fermentation.

As the lactic acid bacteria starter, for example, lactic acid bacteria commonly used in yogurt production, such as Lactobacillus bulgaricus, Lactococcus lactis, and Streptococcus thermophilus, can be used. When the pH reaches the target value, the curd formed is crushed by agitation and cooled to below 10° C. to obtain the fermentation product. By cooling to 10° C. or less, 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 post-heating fermented product (fermented product after heat treatment). By moderately heating the fermented product, it is possible to suppress the production of acid by the lactic acid bacteria in the fermented product after heating. This makes it possible to suppress the decrease in pH during the subsequent manufacturing process and/or during storage of the bifidobacterium-containing concentrated fermented milk, and as a result, it is possible to improve the viability of the bifidobacteria.

Bifidobacterium breve MCC1274 (FERM BP-11175) and prebiotics (lactulose, raffinose, and galacto-oligosaccharides) are then added to the post-heat fermentation 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, more preferably 1×10 ⁸ to 1×10 ¹⁰ cfu, relative to the fermented product after heating. /ml is more preferred. When Bifidobacterium breve MCC1274 (FERM BP-11175) is killed, cfu/mL can be replaced with individual cells/mL.

Bifidobacterium breve MCC 1274 (FERM BP-11175) and prebiotics are added to the post-heat fermentation, followed by concentration. The concentration step can be performed 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 (fermented product after heating with bifidobacteria and prebiotics added) is removed, and the solid content is increased Bifidobacteria and prebiotics-containing concentrated fermented milk is obtained.

By administering the fermented milk obtained as described above, renal dysfunction can be prevented or improved.

[Production Example 5]
A method for producing infant formula to which Bifidobacterium breve MCC1274 (FERM BP-11175) is added is shown below.

10 kg of desalted milk whey protein powder (manufactured by Mirai), 6 kg of milk casein powder (manufactured by Fonterra), 48 kg of lactose (manufactured by Mirai), 920 g of mineral mixture (manufactured by Tomita Seiyaku), and vitamin mixture (manufactured by Tanabe Seiyaku) ), 500 g of lactulose (manufactured by Morinaga Milk Industry Co., Ltd.), 500 g of raffinose (manufactured by Nippon Beet Sugar Co., Ltd.), and 900 g of galacto-oligosaccharide liquid sugar (manufactured by Yakult Pharmaceutical Co., Ltd.) were dissolved in 300 kg of hot water, and further dissolved by heating at 90 ° C. for 10 minutes. , 28 kg of prepared fat (manufactured by Taiyo Yushi Co., Ltd.) was added and homogenized. Thereafter, sterilization and concentration steps were performed, followed by spray drying to prepare about 95 kg of prepared milk powder. To this, 100 g of Bifidobacterium breve MCC1274 (FERM BP-11175) powder (1.8×10 ¹¹ cfu/g, Morinaga Milk Industry Co., Ltd.) dispersed in starch was added. Approximately 95 kg of sugar-blended infant formula is prepared. When the obtained prepared milk powder was dissolved in water to prepare a prepared emulsion with a total solids concentration of 14% (w/v), which is the standard concentration, the number of bifidobacteria in the prepared emulsion was 2.7×10 ^{9 .} cfu/100 mL can be obtained.

Renal dysfunction can be prevented or improved by administering the modified milk powder obtained as described above.

Claims (5)

Bifidobacterium breve as an active ingredient,
The composition for preventing or improving renal dysfunction , wherein the Bifidobacterium breve is Bifidobacterium breve MCC1274 (FERM BP-11175) . 2. The composition of claim 1 , which improves glomerular function. 3. The composition of claim 1 or 2 , which reduces blood creatinine levels. 4. The composition of any one of claims 1-3 , which is a pharmaceutical composition. 4. The composition according to any one of claims 1 to 3 , which is a food or beverage composition.