JP7333732B2 - A composition for maintaining muscle mass and/or muscle strength, or suppressing a decrease in muscle mass and/or muscle strength, and a pharmaceutical composition and a food/drink composition using the composition - Google Patents

Description

NPMD NITE BP-01633

Application of Article 30, Paragraph 2 of the Patent Act Japanese Pharmacology & Therapeutics (2019) Vol. 47 no. 1 p. Published on 97-113

TECHNICAL FIELD The present technology relates to a composition for maintaining muscle mass and/or muscle strength, or suppressing a decrease in muscle mass and/or muscle strength, as well as pharmaceutical compositions and food and drink compositions using the composition.

Conventionally, it is widely recognized that regular exercise is important for maintaining good health. However, the percentage of people who exercise regularly is still at a low level compared to the national population. A significant decrease in muscle mass and strength is observed. Attenuation of muscle mass and muscle strength reduces energy metabolism in daily life, which not only causes lifestyle-related diseases, but can also cause unexpected injuries in daily life.

In addition, when long-term rest is required after surgery or for medical treatment, rapid muscle atrophy and loss of muscle mass may occur, which hinders early return to daily life after recovery. Furthermore, the elderly generally have little muscle mass and muscle strength, and it is desired to maintain or suppress the deterioration of muscle mass and muscle strength in order to live safely.

Steroids, growth hormones, and growth hormone secretagogues are generally known as muscle-enhancing drugs (eg, Patent Document 1). Further, Patent Document 2 discloses a muscle degradation inhibitor containing a specific type of lactic acid bacteria.

WO98/058948 Pamphlet JP 2016-216408 A

As described above, various proposals have been made for methods for maintaining or suppressing a decrease in muscle mass and muscle strength, but side effects are a concern in methods using synthetic compounds, etc., as in Patent Document 1. In addition, as in Patent Document 2, there have already been several reports of methods involving ingestion of probiotic cells or fermentation products, but it is known that probiotics exhibit different physiological effects depending on the strain. have been used, and have not yielded consistent results.

Therefore, the present technology provides a new composition for maintaining muscle mass and/or muscle strength, or suppressing a decrease in muscle mass and/or muscle strength, and a pharmaceutical composition and a food/drink composition using the composition. The main purpose is to

That is, the present technology first provides a composition for maintaining muscle mass and/or muscle strength or suppressing a decrease in muscle mass and/or muscle strength, which contains Lactobacillus paracasei as an active ingredient.
In the present technology, the Lactobacillus paraceasi may be Lactobacillus paraceasi MCC1849 (NITE BP-01633).
Moreover, in the present technology, 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 novel composition for maintaining muscle mass and/or muscle strength or suppressing a decrease in muscle mass and/or muscle strength, as well as pharmaceutical compositions and food and drink compositions using the composition. .
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 maintaining muscle mass and/or muscle strength, or suppressing decrease in muscle mass and/or muscle strength Composition for maintaining muscle mass and/or muscle strength of the present technology, or suppressing decrease in muscle mass and/or muscle strength (hereinafter Also simply referred to as “the composition of the present technology”) is characterized by containing Lactobacillus paracasei as an active ingredient.

Lactobacillus paracasei is one of the species belonging to the genus Lactobacillus.
Since the active ingredient of the composition of the present technology is Lactobacillus paracasei, which has been widely used as a lactic acid bacterium in the field of food and drink, it is highly safe and can be administered continuously for a long period of time. It is very useful because there is little need to worry about side effects. Furthermore, its safety is not impaired even when it is used in combination with other drugs.

Examples of bacteria belonging to Lactobacillus paraceasi include Lactobacillus paraceasi KW3110 (FERM BP-08634), Lactobacillus paraceasi WON0604 (FERM BP-11468), Lactobacillus paraceasi MCC1849 (NITE BP-01633), and the like. However, in the present technology, it is particularly preferable to use Lactobacillus paracasei MCC1849 (NITE BP-01633). In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.

Lactobacillus paracasei MCC1849 (NITE BP-01633) was registered on June 6, 2013 at the National Institute of Technology and Evaluation Biotechnology Center Patent Microorganism Depository (NPMD) (Kazusa Kama, Kisarazu City, Chiba Prefecture 292-0818). 2-5-8 Room 122), deposited under accession number NITE BP-01633, transferred to international deposit under the Budapest Treaty on January 31, 2014, and assigned accession number NITE BP-01633 It is

In addition, the strains identified 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 also referred to as "deposited strains"), and are substantially Equivalent strains (hereinafter also referred to as "derivative strains" or "derived strains") are also included. That is, for example, "Lactobacillus paracasei MCC1849 (NITE BP-01633)" is not limited to the strain itself deposited with the depositary institution under the deposit number of MCC1849 (NITE BP-01633), but is substantially equivalent to it. strains are also included. Regarding strains, "a strain substantially equivalent to the above deposited strain" refers to a strain that belongs to the same species as the above deposited strain and maintains muscle mass and/or muscle strength, which is the effect of the present technology, or maintains muscle mass and/or muscle strength. It means a strain that can obtain the effect of suppressing the decrease of A strain substantially equivalent to the above deposited strain may be, for example, a derivative of 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.

Examples of substantially identical strains and derivative strains include 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 and 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 this technique, muscles can span the entire body from the head to the lower limbs (specifically, head, neck, chest, abdomen, back, upper limbs, lower limbs). In addition, muscle strength includes, for example, grip strength, extension muscle strength, back muscle strength, instantaneous power, muscle endurance, and the like.
In addition, in the present technology, muscle mass or muscle strength can be measured based on a conventionally known method.

In the present technology, "maintenance" refers to preventing the difference from increasing from a certain value for any parameter. Also, "decrease suppression" refers to preventing a difference from occurring when an arbitrary parameter is compared with a certain value.

The composition of the present technology has an effect of maintaining muscle mass and/or muscle strength, or an effect of suppressing a decrease in muscle mass and/or muscle strength, as shown in Examples described later.

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. In addition, because of its high safety, the composition of the present technology is suitable for infants and children, pregnant women, perinatal women, lactating women, elderly people and sick people who are at high risk of losing muscle mass and / or muscle strength. can also be used for

The composition of the present technology may contain a culture containing Lactobacillus paracasei as its active ingredient, Lactobacillus paracasei.

A medium for culturing Lactobacillus paracasei used in the present technology is not particularly limited, and a medium commonly used for culturing bacteria belonging to the genus Lactobacillus can be used.

As the carbon source, for example, sugars such as glucose, galactose, lactose, arabinose, mannose, sucrose, starch, starch hydrolysates, blackstrap molasses, and the like 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. In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.

The culture conditions are not particularly limited as long as the effect of the present technology is not impaired. 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 Lactobacillus paracasei used in the present technology may be used as it is, diluted or concentrated, or collected from the culture. 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. Examples of dead 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, etc.). 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, etc. after crushing. In addition, crushing can be selected from crushing by physical crushing, enzymatic dissolution treatment, chemical treatment, self-dissolution treatment, etc., using methods and equipment known in the art.

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. It is possible to select crushing or the like by damaging the cells with. 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 glycerin 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 of the present technology may consist of only the active ingredient, or may be a composition in which the active ingredient and optional ingredients other than the active ingredient are blended. The optional component is not particularly limited as long as it does not impair the effects of the present technology, and additives conventionally blended in pharmaceuticals (formulation carriers, etc., described later) can be blended.

2. Specific forms of composition of the present technology The composition of the present technology can be used in various forms such as food and drink, pharmaceuticals, quasi-drugs, and feed.

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.

<Beverage composition>
A food and drink composition using the composition of the present technology (hereinafter also simply referred to as "the food and drink composition of the present technology") can be prepared by adding it to a conventionally known food and drink composition. It can also be produced as a new food and drink composition by mixing it with the raw material of the product composition.

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, caramel, candy, gummies, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese confectionery, rice confectionery, bean confectionery, dessert confectionery, and other confectioneries.
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 can be produced in the same manner as ordinary food and drink except for adding the present fungus. can be done. 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.
Here, probiotics generally refer to bacteria that act beneficially in the intestine.

Specifically, for example, Bifidobacterium bacteria, lactic acid bacteria, and the like can be mentioned.
Bifidobacterium bacteria (also referred to as "bifidobacteria") include, for example, Bifidobacterium longum subspecies longum, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium Umm longam subspecies infantis, Bifidobacterium adrecentis, Bifidobacterium catenulatum, Bifidobacterium pseudocatenulatum, Bifidobacterium animalis subspecies animalis, Bifido Bacterium, animalis, subspecies, lactis, and the like. In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.
Examples of lactic acid bacteria include Lactobacillus plantarum, Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus derbilichii subsp. Bacillus rhamnosus, Lactobacillus fermentum, Lactobacillus salivarius, Lactobacillus lactis and the like. In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.

, 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 prebiotic effect that is conventionally known or discovered in the future, or a component that assists the prebiotic effect can be done.
Here, prebiotics generally refer to substances that serve as a selective nutrient source for bacteria that act beneficially in the intestine and promote their proliferation.

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 vitamin C Vitamins such as; creatine; citric acid; fish oil; It can be manufactured by blending with bacterial cells. In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.

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. In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.

The content of Lactobacillus paracasei 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, the content of Lactobacillus paracasei in the food and drink composition may be 1×10 ³ to 1×10 ¹² cfu/g or cfu/ml with respect to the final composition of the food and drink composition. 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 1×10 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 Lactobacillus paracasei 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]
In addition, the food and drink composition of the present technology can be applied to foods with health claims and foods for special uses. 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 food and drink composition of the present technology can be applied to, for example, foods for people with decreased muscle mass or muscle strength, foods for individualized evaluation type sick people, or It can be applied to foods with function claims for healthy people, people in the normal low range of muscle mass and muscle strength indicators, and those with mild symptoms.

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.

The food and drink compositions of this technology include nutrition-adjusted foods such as mother's milk for pregnant and lactating mothers (prepared milk containing well-balanced nutrition necessary for pregnancy and lactating), infant formula, and so on. 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, a bacterial cell powder containing Lactobacillus bacteria, and any one or more selected from the group consisting of probiotics, prebiotics, and powdered milk are mixed to obtain muscle mass and/or muscle strength. To provide a method for producing powdered milk for infants, prepared powdered milk for adults, and milk for mothers, from which powdered milk for maintaining muscle mass and/or suppressing loss of muscle strength is obtained.
Specifically, for example, the present invention provides a method for producing powdered milk for enhancing breast milk components, including the following steps (A) to (C).
(A) culturing a bacterium belonging to the genus Lactobacillus 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) maintaining muscle mass and/or muscle strength, or reducing muscle mass and/or muscle strength by mixing the bacterial cell powder with any one or more selected from the group consisting of probiotics, prebiotics, and powdered milk; Obtaining milk powder for inhibition.

〔supplement〕
Moreover, the food and drink composition of the present technology may be a supplement for maintaining muscle mass and/or muscle strength, or suppressing a decrease in muscle mass and/or muscle strength.

A supplement for maintaining muscle mass and/or muscle strength or suppressing a decrease in muscle mass and/or muscle strength can be produced, for example, by the following method.
That is, the present technology provides, for example, a method for producing a supplement for maintaining muscle mass and/or muscle strength or suppressing a decrease in muscle mass and/or muscle strength, including the following steps (A) and (B).
(A) mixing probiotics and/or prebiotics, Lactobacillus 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 and the like of the present technology can be provided and sold as a food and drink labeled with specific uses (in particular, 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 to perform the above-mentioned display is not only the wording for maintaining muscle mass and / or muscle strength, or suppressing the decrease in muscle mass and / or muscle strength, but also other wording. Also, if the wording expresses the effect of prevention, treatment and / or improvement of various diseases and symptoms related to maintenance of muscle mass and / or muscle strength, or suppression of muscle mass and / or muscle strength decrease, the scope of the present technology It goes without saying that it is included in Such phrases include, for example, maintenance of muscle mass and/or muscle strength, or muscle mass and/or muscle strength for consumers such as "to those who are concerned about muscle mass" and "to those who are concerned about muscle strength". It is also possible to display based on various uses such as to recognize the effect of suppressing the decrease of .

<Pharmaceutical composition, quasi-drug composition>
A pharmaceutical composition or a quasi-drug composition using the composition of the present technology (hereinafter also simply referred to as the "pharmaceutical composition of the present technology") is a conventionally known pharmaceutical or quasi-drug (hereinafter referred to as " (Also referred to as “pharmaceuticals, etc.”).) It can be prepared by adding to the composition, or it can be mixed into the raw materials of the composition such as pharmaceuticals to produce a new composition such as pharmaceuticals.

When the composition of the present technology is used for a composition such as pharmaceuticals, the composition can be appropriately formulated into a desired dosage form according to the administration method such as oral administration or parenteral administration. The dosage form is not particularly limited, and 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 particularly preferable to formulate into a dosage form for oral administration. In addition, formulation can be implemented by a conventionally well-known method according to a dosage form.

At the time of formulation, it may be formulated by appropriately blending formulation carriers. In addition to the composition of the present technology, ingredients such as excipients, pH adjusters, colorants, and corrigents that are commonly used for formulation can be used. Furthermore, it is also possible to use ingredients having preventive, ameliorating and/or therapeutic effects on diseases or symptoms that have been known in the past or will be found in the future, as long as they do not impair the effects of the present technology, depending on the purpose. .

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; In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.

Examples of binding agents include gelatin, polyvinylpyrrolidone, macrogol, etc., in addition to the excipients described above. In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.
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. In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.

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. In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.

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; In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.
Flavoring agents include, for example, sweeteners, acidulants, flavoring agents, and the like. In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.
In the case of liquid preparations for oral administration, carriers used include solvents such as water, flavoring agents, and the like. In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.

The content of Lactobacillus paracasei 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, the content of Lactobacillus paracasei in the pharmaceutical composition may be 1×10 ³ to 1×10 ¹² cfu/g or cfu/ml with respect to the final composition of the pharmaceutical composition. 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 1×10 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 Lactobacillus paracasei per packaging unit.

<Feed composition>
A feed composition using the composition of the present technology can be prepared by adding it to a conventionally known feed composition, or can be mixed into the ingredients of the feed composition to produce a new feed composition. can.

When the composition of the present technology is used as a feed composition, raw materials for the feed composition include, for example, cereals such as corn, wheat, barley, and rye; brans such as bran, wheat bran, rice bran, and defatted rice bran; corn gluten. Manufacturing lees such as 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 feed such as calcium phosphate and calcium carbonate; Fats and oils; Amino acids; etc. Examples of the form of feed include pet feed (pet food, etc.), livestock feed, fish feed, and the like.

The content of Lactobacillus paracasei in the feed composition of the present technology can be freely set according to body weight and the like as long as the effects of the present technology are not impaired. In the present technology, the content of Lactobacillus paracasei in the feed composition is more preferably 1×10 ³ to 1×10 ¹² cfu/g with respect to the final composition of the feed composition. 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 1×10 ¹⁰ It is preferable to add at least cfu/day or more.

<Others>
The composition of the present technology may contain carbohydrates, dietary fibers, nucleic acids, vitamins, minerals, etc. that are generally acceptable for the purpose of nutritional supplementation in foods, beverages, pharmaceuticals, etc., or feeds. Carbohydrates include, for example, dextrin, sucrose, glucose, fructose, maltose, lactulose, raffinose and the like. Dietary fibers include, for example, cellulose, indigestible dextrin, gum arabic and the like. Nucleic acids include, for example, nucleotides, nucleosides, DNA, RNA, bases and the like. Examples of vitamins include vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, niacin, pantothenic acid, folic acid, β-carotene, and the like. A vitamin mixture (manufactured by Tanabe Seiyaku Co., Ltd., etc.) may also be used. Minerals include, for example, phosphorus, calcium, sodium, potassium, chlorine, magnesium, iron, copper, zinc, and manganese, and commercially available mineral mixtures (manufactured by Tomita Seiyaku Co., Ltd., etc.) may also be used. In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.

The present technology can also employ the following configuration.
[1]
A composition for maintaining muscle mass and/or muscle strength, or suppressing a decrease in muscle mass and/or muscle strength, containing Lactobacillus paracasei as an active ingredient.
[2]
The composition of [1], wherein the Lactobacillus paracasei is Lactobacillus paracasei MCC1849 (NITE BP-01633).
[3]
The composition of [1] or [2], which is a pharmaceutical composition.
[4]
The composition according to [1] or [2], which is a food or drink composition.
[5]
The composition according to [3], which contains 10 ⁶ to 10 ¹² cfu of Lactobacillus paracasei per packaging unit.
[6]
The composition of [4], comprising 10 ⁶ to 10 ¹² cfu of Lactobacillus paracasei per serving.
[7]
The composition of [5] or [6], which is fermented milk.
[8]
Maintenance of muscle mass and/or muscle strength, or inhibitor of decrease in muscle mass and/or muscle strength, medicament for maintaining muscle mass and/or muscle strength, or suppression of decrease in muscle mass and/or muscle strength, or muscle mass and/or muscle strength or use of Lactobacillus paracasei in foods and drinks for maintaining muscle mass and/or muscle strength.
[9]
The use of [8], wherein the Lactobacillus paracasei is Lactobacillus paraceasi MCC1849 (NITE BP-01633).
[10]
A method for maintaining muscle mass and/or muscle strength or suppressing a decrease in muscle mass and/or muscle strength, comprising administering Lactobacillus paracasei to a subject.
[11]
The method of [10], wherein the Lactobacillus paracasei is Lactobacillus paraceasi MCC1849 (NITE BP-01633).

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]
<Production of sample>
A nutritional supplement drink (energy replenishing liquid food) having a content of 125 ml was produced by a conventional method based on the composition and amount of ingredients shown in Table 1 below. More specifically, milk raw materials, optionally water, and other ingredients were mixed, and the mixture was homogenized and heat sterilized by a conventional method to produce a sterilized emulsion. Next, heat-sterilized bacterial powder of Lactobacillus paracasei MCC1849 (NITE BP-01633) strain was added to the heat-sterilized sterilized emulsion, and after cooling, this was used as a test sample.
On the other hand, as a control sample, a fruit juice drink (100% orange juice: manufactured by Megmilk Snow Brand) was used.
Table 1 below shows the composition and amount of components per bottle (125 ml) of the test sample and the control sample.

<Subject>
Japanese males and females who were 65 years of age or older at the time of obtaining informed consent and who felt tired on a daily basis were enrolled in the clinical trial as subjects. Furthermore, 62 subjects who did not meet the following exclusion criteria were selected by blood tests and interviews by doctors, and used as subjects.
(1) Those who are being treated or have a history of malignant tumor (2) Those who are being treated or have a history of autoimmune disease (3) Those who are being treated or have a history of inflammatory bowel disease (4) Hospitalized (5) Persons who regularly consume foods for specified health use or foods with function claims (6) Persons who routinely consume foods/drinks containing natto, yogurt, and lactic acid bacteria (7) Smokers (8) (9) Persons who regularly use foods/beverages such as supplements that are considered functional other than foods for specified health uses and foods with function claims (10) Allergies (drugs, test foods (11) Subjects who are pregnant, breastfeeding, or intend to become pregnant during the study period (12) Subjects who have participated in other clinical studies in the 3 months prior to the date of informed consent (13) In addition, those who are judged to be inappropriate for this study by the investigator

Each subject was assigned based on a randomization table prepared by the randomization officer. The allocation in this experimental example was a stratified random allocation using the immunity score (manufactured by Kenko Life Science), age, and sex as allocation adjustment factors, and 31 subjects were randomly allocated to each of the test sample group and the control sample group.

<Test method>
The test sample produced or the control sample was taken once daily after breakfast. The intake period was 4 weeks. The number of Lactobacillus paracasei MCC1849 (NITE BP-01633) strains contained in the test sample was 10 billion per day (one tube). That is, the daily intake was set at 10 billion heat-killed bodies of Lactobacillus paracasei MCC1849 (NITE BP-01633) strain.

For each subject, muscle mass and grip strength were measured before sample intake (baseline: week 0) and 4 weeks after sample intake. A body component analyzer ZEUS 9.9 (manufactured by Kobe Medicare Co., Ltd.) was used to measure muscle mass, and a digital grip dynamometer Grip D TKK5401 (manufactured by Takei Kiki Kogyo Co., Ltd.) was used to measure grip strength.
Drinking alcohol and excessive exercise were prohibited from the day before the measurement to the end of the measurement on the day. The subject's health condition was confirmed by interview on the day of measurement, and the intake status of the sample was confirmed by a diary recorded daily.

<Statistical analysis>
Subjects whose intake rate of the test sample or control sample was less than 90% and those who significantly deviated from the protocol were excluded from the analysis, and PPS (Per Protocol set) analysis was performed.

<Persons subject to analysis>
There were no subjects whose ingestion rate was less than 90% during the sample intake period, but there was one person in each group who could not confirm the presence or absence of intervention because the test diary was not submitted and the sample was not returned after the start of the experiment. were excluded from the analysis. Therefore, the population to be analyzed includes 30 test sample groups (10 men, 20 women, average age 69.5 ± 4.4 years old), 30 control sample groups (10 men, 20 women, average age 69 .4±4.9 years).

<Result 1>
Table 2 below shows the measurement results of the maximum grip strength before and 4 weeks after the intake.

mean ± standard deviation

After 4 weeks of ingestion, the maximum grip strength decreased from baseline to −0.8±2.6 kg in the control sample group, while the maximum grip strength was maintained at 0.1±2.7 kg in the test sample group. Therefore, it was suggested that the ingestion of a composition containing Lactobacillus paracasei as an active ingredient maintains or suppresses the decrease in muscle strength.

<Result 2>
Table 3 below shows the measurement results of muscle mass before and after 4 weeks of ingestion.

mean ± standard deviation

After 4 weeks of ingestion, muscle mass decreased from baseline to −0.1±1.4 kg in the control sample group, while muscle mass was maintained at 0.0±1.5 kg in the test sample group. Therefore, it was suggested that the ingestion of a composition containing Lactobacillus paracasei as an active ingredient maintains or suppresses the decrease in muscle mass.

[Manufacturing example]
Below, production examples of pharmaceutical compositions and food compositions using the composition of the present technology are shown.

[Production Example 1]
Lactobacillus paracasei MCC1849 (NITE BP-01633) 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 lyophilized bacterial powder (bacterial powder). get 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 maintaining muscle mass and/or muscle strength or inhibiting a decrease in muscle mass and/or muscle strength. Administration of the composition can maintain muscle mass and/or muscle strength, or suppress loss of muscle mass and/or muscle strength.

[Production Example 2]
Lactobacillus paracasei MCC1849 (NITE BP-01633) 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 lyophilized bacterial powder (bacterial powder). get 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 maintaining muscle mass and/or muscle strength or inhibiting a decrease in muscle mass and/or muscle strength. Administration of the composition can maintain muscle mass and/or muscle strength, or suppress loss of muscle mass and/or muscle strength.

[Production Example 3]
Lactobacillus paracasei MCC1849 (NITE BP-01633) 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 lyophilized bacterial powder (bacterial powder). get Next, prebiotics (lactulose, raffinose and galacto-oligosaccharides) and crystalline cellulose are put into 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, muscle mass and/or muscle strength can be maintained, or decrease in muscle mass and/or muscle strength can be suppressed.

[Production Example 4]
A method for producing fermented milk to which Lactobacillus paracasei MCC1849 (NITE BP-01633) 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. After heat sterilization, the lactic acid bacteria starter is added (inoculated) to the sterilized emulsion cooled to a certain temperature and mixed. After being filled in a container or the like, it is fermented at a predetermined fermentation temperature. 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. In the present technology, one of these may be used alone, or two or more may be used in arbitrary combination.
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 lactic acid can be suppressed.
Next, the fermented product obtained in the fermentation step is heat-treated to such an extent that the lactic acid bacteria are not killed, 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 lactic acid by lactic acid bacteria in the fermented product after heating. In addition, it is possible to suppress the decrease in pH during subsequent production steps and/or during storage of the concentrated fermented milk.

Next, Lactobacillus paracasei MCC1849 (NITE BP-01633) and prebiotics (lactulose, raffinose and galacto-oligosaccharides) are added to the post-heating fermented product obtained in the heat treatment step. The amount of Lactobacillus paracasei MCC1849 (NITE BP-01633) to be added is preferably 1×10 ⁷ to 1×10 ¹¹ cfu/ml, more preferably 1×10 ⁸ to 1×10 ¹⁰ cfu/ml of the fermented product after heating. is more preferred. If Lactobacillus paracasei MCC1849 (NITE BP-01633) is killed, cfu/mL can be replaced with individual cells/mL.
Then, Lactobacillus paracasei MCC1849 (NITE BP-01633) and prebiotics are added to the heated fermented product and concentrated. The concentration step can be performed by appropriately using a conventionally known concentration method. For example, a centrifugal separation method, a membrane separation method, or the like can be used. In the centrifugation method, whey in the concentrate (fermented product after heating to which lactic acid bacteria and prebiotics are added) is removed, and concentrated fermented milk containing lactic acid bacteria and prebiotics with an increased solid content concentration is obtained. .
By administering the fermented milk obtained as described above, muscle mass and/or muscle strength can be maintained, or decrease in muscle mass and/or muscle strength can be suppressed.

A method for producing infant formula to which Lactobacillus paracasei MCC1849 (NITE BP-01633) 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), vitamin mixture (manufactured by Tanabe Seiyaku) 32 g, 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 powdered Lactobacillus paracasei MCC1849 (NITE BP-01633) powder (1.8×10 ¹¹ cfu/g, manufactured by Morinaga Milk Industry Co., Ltd.) dispersed in starch was added to prepare a mixture of lactic acid bacteria and oligosaccharides. Prepare approximately 95 kg of milk powder. When the obtained prepared milk powder was dissolved in water to prepare a prepared emulsion with a total solid concentration of 14% (w/v), which is the standard concentration, the number of lactic acid bacteria in the prepared emulsion was 2.7 × 10 ⁹ cfu. /100 mL can be obtained.
By administering the infant formula obtained as described above, it is possible to maintain muscle mass and/or muscle strength, or to suppress a decrease in muscle mass and/or muscle strength.

Claims (3)

Contains Lactobacillus paracasei,
A composition for maintaining muscle mass and/or muscle strength, or suppressing a decrease in muscle mass and/or muscle strength , wherein the Lactobacillus paracasei is Lactobacillus paracasei MCC1849 (NITE BP-01633) . 2. The composition of claim 1 , which is a pharmaceutical composition. The composition according to claim 1 , which is a food or beverage composition.