JP2017149696A - Muscular damage healing-promoting composition containing lactoferrin and application method thereof - Google Patents

Abstract

[PROBLEMS] To actively promote the proliferation and differentiation of myoblasts, which are involved in healing in muscle damage and atrophy, and further promote hypertrophy to myotube cells to form muscle fibers. Providing a highly safe composition that accelerates muscle recovery and strengthening, effectively heals muscle damage and atrophy, and significantly reduces the risk of side effects. Is an issue.
A composition for promoting the proliferation, differentiation and hypertrophy of muscle cells, comprising a component derived from lactoferrin. Because it promotes all three of the muscle regeneration processes, a single composition can effectively provide muscle strengthening and recovery.
[Selection figure] None

Description

  The present invention relates to a pharmaceutical composition or a food composition that promotes proliferation, differentiation, and hypertrophy of myoblasts in order to promote healing of damaged or atrophied muscle containing a component derived from lactoferrin.

  With the recent rapid aging of the population, prevention of locomotive syndrome and metabolic syndrome is regarded as important. Locomotive syndrome and metabolic syndrome are caused by a decrease in motor function and accumulation of visceral fat, respectively, and are greatly related to the causative diseases in which elderly people require nursing care.

  Also, if you are forced to bed and rest for a long time due to an injury or illness such as a fracture, muscle atrophy occurs, it takes time to return to daily life, and in some cases, it may interfere with daily life is there. Even in health, muscle atrophy may occur due to lack of daily exercise or aging, and it may similarly impede daily life.

  Since skeletal muscle is a major organization responsible for motor function and energy metabolism, maintaining and strengthening skeletal muscle is important for living an independent and healthy life.

  If you are healthy or have recovered your health, gradually resuming exercise will restore your muscles both quantitatively and qualitatively, but recovery will take time. On the other hand, it is very difficult for the sick and the elderly to strengthen the contracted muscles.

  Muscular atrophy significantly reduces the so-called quality of life, whether it is a sick person, an elderly person, or a healthy person, so it is required to recover muscle mass quickly and strengthen the muscle by some means. Yes. For this reason, muscle enhancers that can be ingested as pharmaceutical muscle enhancers or supplements are provided. These supplements are composed of muscle nutrients such as proteins and amino acids, and are intended to strengthen muscles by supplemental intake of those nutrients. However, since muscle atrophy is not caused by a lack of nutrients, it is unlikely that a muscle strengthening supplement will actually have a significant effect.

  Moreover, the thing which has arginine, a lysine, ornithine as an active ingredient is proposed for what has other than a muscle nutrient as a main component (patent document 1). This is based on the knowledge that a specific amino acid promotes the secretion of growth hormone and testosterone. The hormone is secreted by ingestion and indirectly increases muscle by the action of the hormone. . This supplement promotes the secretion of growth hormone and testosterone and indirectly strengthens muscles by the action of the hormone. The muscle-enhancing agent intended to restore and strengthen the atrophied muscle must be safe even for long-term use, but the ingredients themselves are safe for this supplement, but the hormone Since it controls the amount of secretion, it is difficult to adjust the dose compared with the case of direct action. In addition, since this supplement indirectly increases muscle mass by promoting secretion of hormones, it is not a direct action mechanism and a significant effect cannot be expected.

  As other muscle enhancing agents, those having specific polypeptides, polypeptide compounds, and specific polypeptide factors as active ingredients have been proposed (Patent Document 2). This is a pharmaceutical that prevents diseases and disorders by inducing mitogenesis, growth and differentiation of myocytes.

  In addition, a component having an action of promoting proliferation and differentiation of myoblasts from animal and plant extracts and compounds whose safety has been confirmed has been proposed (Patent Document 3).

  It is well known that cells forming muscle (muscle cells) are fibrous, and are also called muscle fibers. It has been found that myoblasts proliferate and differentiate into myotubes, and that myotubes enlarge and grow to form myofibers. Therefore, an agent that promotes myoblast proliferation, differentiation, and hypertrophy is considered effective for muscle augmentation.

  From this point of view, Patent Document 3 proposes enhancement of muscle because it promotes proliferation (division) and differentiation of muscle cells, but does not propose hypertrophy to muscle fibers. Therefore, the muscle formation effect cannot be expected from the actual promotion of myoblast activity.

  Lactoferrin is an iron-binding protein with a molecular weight of about 80,000 that is contained in a very large amount in breast milk and is known to exhibit antibacterial activity against harmful microorganisms such as Escherichia coli, Candida, Clostridium, and Staphylococci. (Non-patent Document 1), and it has been proposed to be blended into an edible composition for childcare (Patent Document 4). Further, prevention of pathogenic bacteria adherence to cells (Patent Document 5), antiviral action (patent) Document 6), immunostimulation (Patent Document 7), anti-tumor (Non-Patent Document 2), anti-rheumatic (Patent Document 8), obesity prevention (Non-Patent Document 3), bone formation promoting action (Non-Patent Document 4), etc. It is known to have various actions.

  However, reports on the fact that lactoferrin has an effect of promoting muscle formation and an effect of promoting proliferation, differentiation and hypertrophy to myoblasts are not disclosed in any literature. It has also been found that lactoferrin has no side effects even after long-term ingestion.

JP 2004-256513 A JP 2004-043437 A JP 2008-156294 A Japanese Unexamined Patent Publication No. 1-93534 JP-A-3-220130 JP-A-1-233226 JP-A-7-179355 JP-A-5-186368

Journal of Pediatics, 94, 1 page, 1979 Cancer Research, 54, 2310, 1994 British Journal of Nutrition, 91, 533, 2004 Clinical Medicine & Research, 3 volumes, 93 pages, 2005

  The present invention actively promotes the proliferation and differentiation of myoblasts involved in healing in muscle damage / atrophy, and further promotes hypertrophy of myotube cells to the recovery and enhancement of muscles forming muscle fibers. It is an object of the present invention to provide a highly safe composition that achieves a shortening of the above and has a significantly reduced risk of side effects.

  As a result of intensive studies in view of the above problems, the present inventor has dramatically increased the proliferation of myoblasts by causing lactoferrin-derived components having no side effects to act on myoblasts. The present inventors have solved the above problems by finding three promoting effects that promote differentiation / fusion into cells and hypertrophy into muscle fibers. The composition of the present invention is highly safe with significantly shortening the time for muscle strengthening by significantly promoting the activity of cells in three processes in muscle recovery and strengthening, and significantly reducing the risk of side effects. A composition is provided.

In order to solve the above problems, the present invention provides the following.
[1] In one aspect, the present invention provides a pharmaceutical composition for indirect administration for recovering from damage in muscle cells, comprising a component derived from lactoferrin.
[2] In one embodiment, the indirect administration is oral administration, tube administration or enteral administration.
[3] In one embodiment, the component is lactoferrin.
[4] In one aspect, the present invention provides a food composition for recovering from damage in muscle cells, comprising a component derived from lactoferrin.

  According to the present invention, a highly safe composition that actively promotes the regenerative ability of a living body related to healing of muscle damage, achieves muscle strengthening and shortening of formation time, and significantly reduces the risk of side effects. Is provided.

FIG. 1 is a comparison of myoblast proliferation promoting effects. C2C12 cells were compared with Comparative Example 1 (without addition of lactoferrin), Comparative Example 2 (lactoferrin 1 microgram / ml), Comparative Example 3 (lactoferrin 10 microgram / ml), Example 1 (in the presence of lactoferrin 100 microgram / ml). It is the figure which culture | cultivated and evaluated cell growth ability over time using Alamar Blue. FIG. 2 shows C2C12 cells in Comparative Example 1 (without addition of lactoferrin), Comparative Example 2 (lactoferrin 1 microgram / ml), Example 3 (lactoferrin 10 microgram / ml), and Example 1 (lactoferrin 100 microgram / ml). Is a diagram in which differentiation was induced with DMEM (2% Horse Serum, 100 units / ml penicillin, 100 micrograms / ml streptomycin) containing, and cells were collected after culturing for 4 days, and expression of muscle differentiation markers was confirmed by Western blotting. is there. FIG. 3 shows D2 (2% Horse Serum, 100 units / ml) containing C2C12 cells seeded on a 24 wells plate and reaching saturation, and containing Comparative Example 1 (without lactoferrin) and Example 1 (lactoferrin 100 microgram / ml). After exchanging the medium with penicillin (100 microgram / ml streptomycin) and culturing for 4 days, fluorescent immunostaining of MyHC was performed. The number of nuclei stained with MyHC in two or more myotubes was determined by DAPI. It is the figure which calculated | required Fusion Index in the ratio of the total number. FIG. 4 shows that myotubes were obtained by inducing differentiation with DMEM (2% Horse Serum, 100 units / ml penicillin, 100 microgram / ml streptomycin) after inoculating C2C12 cells seeded on 24 wells plate and reaching saturation. After the cells were formed, in DMEM (2% Horse Serum, 100 units / ml penicillin, 100 microgram / ml streptomycin) containing Comparative Example 1 (no lactoferrin added) and Example 1 (lactoferrin 100 microgram / ml) It is the figure which calculated | required Myotube diameter by carrying out the fluorescence immunostaining of MyHC after measuring a cell for 4 days, and measuring the short diameter of a myotube cell.

  The lactoferrin-derived component used in the present invention includes commercially available lactoferrin, animal milk, lactoferrin separated from human milk by a conventional method, and apolactoferrin from which iron is removed from the lactoferrin by a conventional method, or a mixture thereof Either may be sufficient. Moreover, any of a degradation product obtained by hydrolyzing the lactoferrin with an acid / alkali or an enzyme by a conventional method, a product obtained by purifying the hydrolyzate by a conventional method, or a mixture thereof may be used. Moreover, the said lactoferrin and its hydrolyzate can also be mixed and used.

The form of lactoferrin used in the present invention may be a commercially available product as it is, may be enteric-coated, and is a surfactant component (sucrose fatty acid ester, glycerin fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester) , Lecithin, saponin, sodium caseinate, oxyethylene fatty acid alcohol, sodium oleate, polyoxyethylene higher fatty acid alcohol, sophorose lipid, etc., partly modified in three-dimensional structure, fats and oils (medium chain fatty acid, palm oil, palm Oil, rapeseed oil, sesame oil, sesame oil), a surfactant component and lactoferrin may be mixed and dispersed.

One of the above may be used alone, or two or more may be used in appropriate combination.

(Pharmaceutical composition)
The pharmaceutical composition of the present invention may further comprise pharmaceutically acceptable raw materials. Examples include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose derivatives, tragacanth, gelatin, syrup, methyl hydroxybenzoate, talc , Magnesium stearate, water, mineral oil and the like. The pharmaceutical composition of the present invention may contain one or more of these raw materials.

  The pharmaceutical composition of the present invention is one of other ingredients including a lubricant, an emulsifier, a suspending agent, an antioxidant, an antiseptic, a sweetener and a flavoring agent, and water-soluble vitamins and oil-soluble vitamins. May contain more than species.

  The pharmaceutical composition of the present invention is produced by methods well known in the art. For example, it may be produced by a method including a step of adding pure lactoferrin, or may be produced by a method including a step of adding a composition containing lactoferrin.

  The form of the pharmaceutical composition of the present invention is not particularly limited. Examples of the form of the pharmaceutical composition of the present invention include forms such as tablets, pills, powders, syrups, emulsions, solutions, suspensions, gelatin capsules, sprays and the like. . Pharmaceutical compositions in the form of sprays and the like can also be administered by routes such as intranasal.

  The general preparation method of the pharmaceutical composition of this invention is shown below.

  The lactoferrin-derived component-containing composition of the present invention can be blended with a pharmaceutically acceptable carrier and administered orally, if necessary, or as an injection, suspension, solution, spray, etc. It can be administered parenterally as a liquid formulation. Pharmaceutically acceptable carriers include excipients, lubricants, binders, disintegrants, disintegration inhibitors, absorption enhancers, adsorbents, humectants, stabilizers, solvents, solubilizers, suspensions Agents, tonicity agents, buffers, soothing agents and the like. In addition, formulation additives such as preservatives, antioxidants, colorants, sweeteners and the like can be used as necessary. Moreover, it is also possible to mix | blend substances other than the component derived from a lactoferrin with the composition of this invention.

  Examples of the excipient include glucose, lactose, sucrose, D-mannitol, crystalline cellulose, starch, calcium carbonate, light anhydrous silicic acid, sodium chloride, kaolin and urea.

  Examples of the absorption promoter include, but are not limited to, quaternary ammonium bases and sodium lauryl sulfate.

  Examples of the stabilizer include, but are not limited to, human serum albumin and lactose.

  Preferable examples of the solvent in the liquid preparation include water for injection, alcohol, propylene glycol, macrogol, sesame oil and corn oil.

  Preferable examples of solubilizing agents in liquid preparations include surfactants such as stearyl triethanolamine, sodium lauryl sulfate, lauryl aminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glyceryl monostearate, such as polyvinyl Examples include, but are not limited to, hydrophilic polymers such as alcohol, polyvinylpyrrolidone, carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose.

  Preferable examples of the isotonic agent in the liquid preparation include, but are not limited to, sodium chloride, glycerin, D-mannitol and the like.

  Preferable examples of the buffer in the liquid preparation include, but are not limited to, buffers such as phosphate, acetate, carbonate and citrate.

  Preferable examples of the soothing agent in the liquid preparation include, but are not limited to, benzyl alcohol, benzalkonium chloride, procaine hydrochloride and the like.

  Preferable examples of the preservative in the liquid preparation include, but are not limited to, sulfite, ascorbic acid, alpha tocopherol and cysteine.

  When prepared as an injection, solutions and suspensions are preferably sterilized and isotonic with blood or other media at the intended infusion site. Usually, these are sterilized by filtration using a bacteria retention filter or the like, blending with a bactericidal agent, or irradiation. Furthermore, after these treatments, solidify by freeze-drying or other methods, and add sterile water or sterile diluent for injection (lidocaine hydrochloride aqueous solution, physiological saline, aqueous glucose solution, ethanol, or a mixed solution thereof) just before use. May be.

  Furthermore, if necessary, the pharmaceutical composition may contain coloring agents, preservatives, flavors, flavoring agents, sweeteners, and the like, as well as other agents.

  In another embodiment, in the present invention, infusion can be performed intravenously or subcutaneously. When administered systemically, the medicament used in the present invention may be in the form of a pharmaceutically acceptable aqueous solution free of pyrogens. Such a pharmaceutically acceptable composition can be easily prepared by those skilled in the art by considering pH, isotonicity, stability and the like.

  The amount of the composition used in the method of the present invention is determined in consideration of the purpose of use, the target disease (type, severity, etc.), the patient's age, weight, sex, medical history, cell morphology or type, etc. A person skilled in the art can easily determine. The frequency of applying the method of the present invention to a subject (or patient) also considers the purpose of use, target disease (type, severity, etc.), patient age, weight, gender, medical history, treatment course, etc. Thus, it can be easily determined by those skilled in the art. Examples of the frequency include administration every day to once every several months (for example, once a week to once a month). It is preferable to administer once a week to once a month while observing the course.

  The lactoferrin used in the present invention is usually 50 mg to 5,000 mg / day as the amount of human intake per day. This dose is not limited as long as it promotes muscle healing. This dose is preferably administered in one or several divided doses, but is not necessarily limited thereto. The actual dose is determined in consideration of the subject's age, weight and severity of symptoms, and the selected route of administration.

  The pharmaceutical composition of the present invention may be administered alone or in combination with other therapeutic agents. The combination can be administered, for example, either simultaneously as a mixture; simultaneously or concurrently but separately; or over time.

(Food composition)
The composition of the present invention can be used as a food itself having a sweetness and muscle damage healing promoting effect, or as an additive such as a seasoning (such a composition is referred to as a food composition). The food composition of the present invention can be used as a health food, a dietary supplement, and a special-purpose food (a food for specified health use).

  The food composition of the present invention may further contain food ingredients that are usually used in the art. Examples of food ingredients include lactose, dextrose, sucrose, sorbitol, mannitol, apple fiber, soybean fiber, meat extract, black vinegar extract, gelatin, corn starch, honey, animal and vegetable oils, polysaccharides, grains, vegetables, fruit vegetables, fruits, Examples include meat, eggs, dairy products, seaweed, and processed products thereof. The composition of the present invention may contain one or more of these food ingredients.

  The food composition of the present invention is a component such as a lubricant, an emulsifier, a suspending agent, an antioxidant, an antiseptic, a sweetener, and a flavoring agent in addition to the above-mentioned food ingredients, as in the case of the above-mentioned pharmaceutical product. One or more of the following. Further, it may further contain other components including water-soluble vitamins and oil-soluble vitamins. One skilled in the art can readily select appropriate components that do not interfere with the action of lactoferrin.

  The food composition of the present invention is produced by a method well known in the art. For example, you may manufacture by the method including the process of adding the pure lactoferrin which has an effect | action, and may manufacture by the method including the process of adding the composition containing the lactoferrin which has an effect | action.

  The form of the food composition of the present invention is not particularly limited. Examples of the form of the food composition of the present invention include granules, tablet confectionery, jelly, rice cake, and beverage.

  The food composition of the present invention is ingested as necessary, and may be ingested every day like a medicine basket, or once a day, once a week, once a month, etc. It may be taken at long intervals. Preferably, three meals are taken per day.

  The lactoferrin used in the food composition of the present invention is usually 50 mg to 5,000 mg / day as the daily human intake. This dose is not limited as long as it promotes muscle healing. This dose is preferably administered in one or several divided doses, but is not necessarily limited thereto. The actual dose is determined in consideration of the subject's age, weight and severity of symptoms, and the selected route of administration.

The present invention relates to muscle enhancement such as corn-derived protein, wheat-derived protein, collagen-derived protein, soybean-derived protein, whey-derived protein and hydrolyzate thereof, amino acid (valine, leucine, isoleucine). It is also possible to combine the nutrients with lactoferrin-derived components, and as a result, an additive / synergistic effect can be expected with respect to the effect on muscle cells as compared with the case where each is used alone.

The present invention relates to sugars such as monosaccharides such as glucose, disaccharides such as maltose, sugar alcohols such as erythritol and xylitol, polysaccharides such as oligosaccharides, Rakan fruit glycosides, aspartame, sucralose, and acesulfame K. It is also possible to combine substances that serve as energy sources with the components derived from lactoferrin, and the combination can be expected to have an additive / synergistic effect on muscle enhancement.

In the present invention, it is also possible to combine a substance serving as an energy source, such as medium chain fatty acid, palm oil, coconut oil, rapeseed oil, sesame oil, and sesame oil, with a component derived from lactoferrin as a lipid. A synergistic effect can be expected.

In the present invention, substances that protect or strengthen cells such as oligometric proanthocyanidins (OPC), resveratrol, vitamin C, and vitamin E can be combined with lactoferrin-derived components as antioxidants. Addition and synergistic effect of muscle strengthening effect can be expected by combination.

In the present invention, it is also possible to combine an indigestible dextrin having an action of promoting absorption of calcium and minerals with a lactoferrin-derived component, and an additive / synergistic effect of muscle strengthening effect can be expected by the combination.

References such as scientific literature, patents and patent applications cited herein are hereby incorporated by reference in their entirety to the same extent as if each was specifically described.

The present invention has been described with reference to the preferred embodiments for easy understanding. In the following, the present invention will be described based on examples, but the above description and the following examples are provided only for the purpose of illustration, not for the purpose of limiting the present invention. Accordingly, the scope of the present invention is not limited to the embodiments or examples specifically described in this specification, but is limited only by the scope of the claims.

  Mouse myoblast cell line C2C12 (RIKEN Bioresource Center) was used as the target myoblast. As the medium, Dulbecco's modified Eagle's medium-low glucose (DMEM, Sigma-Aldrich Co. LLC.) Was used.

  In each test, myoblasts were prepared as Comparative Example 1, lactoferrin 1 microgram / ml as Comparative Example 2, lactoferrin 10 microgram / ml as Comparative Example 3, and lactoferrin 100 microgram / ml as Example 1 without addition of lactoferrin. The test for confirming the effect of promoting proliferation, differentiation and hypertrophy was conducted.

<Experimental Example 1 Proliferation Promoting Effect of Lactoferrin on Myoblasts>
C2C12 cells were seeded on 48 wells plate at 0.5 × 10 3 cells / cm 2 and cultured in DMEM (2.5% Fetal Bovine Serum, 100 units / ml penicillin, 100 microgram / ml streptomycin). The cells were cultured overnight to adhere, and the lactoferrin of Comparative Examples 1 to 3 and Example 1 was added on the 0th day. Every two days, the medium was replaced with fresh medium containing lactoferrin. After culturing in DMEM (2.5% Fetal Bovine Serum, 100 units / ml penicillin, 100 microgram / ml streptomycin) without phenol red on the second day, the fourth day, and the sixth day, Alamar Blue (Trec Diagnostics, The final concentration was 5%). Thereafter, the fluorescence intensity of the medium was measured using Fluoro Scan Ascent FL (Thermo Fisher Scientific, Waltham, USA) at an excitation wavelength of 544 nm and a fluorescence wavelength of 590 nm to evaluate cell proliferation ability. Judgment was ◎ (significant difference from Comparative Example 1 from the second day: significance level 5%), ○ (significant difference from Comparative Example 1 on the sixth day: significance level 5%), × ( It was determined that there was no significant difference from Comparative Example 1 until the sixth day).

<Experimental Example 2 Differentiation Promoting Effect of Lactoferrin on Myoblasts>
In order to examine the effect of lactoferrin on muscle differentiation of C2C12 cells, C2C12 cells that reached saturation were treated with DMEM (2% Horse Serum, 100 units / ml) containing the lactoferrin of Comparative Examples 1 to 3 and Example 1. Differentiation was induced with penicillin (100 microgram / ml streptomycin), and after 4 days of culture, the cells were collected and evaluated for expression of myosin heavy chain (MyHC), a muscle differentiation marker, by Western blotting. Judgment was made by ◎ (significantly more expressed than Comparative Example 1), ○ (expressed more than Comparative Example 1), × (expressed less than Comparative Example 1).

<Experimental Example 3 Measurement of Fusion index as differentiation index of myotube cell>
C2C12 cells that had been seeded in 24 wells plate and reached saturation state were changed to DMEM (2% Horse Serum, 100 units / ml penicillin, 100 microgram / ml streptomycin) containing the lactoferrin of Comparative Example 1 and Example 1, After culturing for 4 days, fluorescence immunostaining of MyHC was performed, and the number of nuclei contained in two or more myotubes containing nuclei stained with MyHC was determined as 4 ′, 6-diamidino-2-phenyllinole (DAPI, fluorescent dye). The Fusion Index was determined by dividing by the total number of (single, strongly binding to DNA). Judgment was made by ○ (significantly different from comparative example 1: significant level 5%), × (significantly different from comparative example 1).

<Experimental Example 4 Effect of Lactoferrin on Hypertrophy>
C2C12 cells that reached the saturation state after seeding on 24 wells plate were induced to differentiate with DMEM (2% Horse Serum, 100 units / ml penicillin, 100 microgram / ml streptomycin) and cultured for 6 days to form myotube cells Then, after culturing the cells with DMEM (2% Horse Serum, 100 units / ml penicillin, 100 microgram / ml streptomycin) containing the lactoferrin of Comparative Example 1 and Example 1, myHC fluorescence immunostaining was performed. Myotube diameter, which is an index of muscle hypertrophy, was determined by measuring the short diameter of the duct cells. Judgment was made by ○ (significantly different from comparative example 1: significant level 5%), × (significantly different from comparative example 1).

The results of Experimental Example 1 to Experimental Example 4 are shown in Table 1 and FIGS.

From these results, the action of the lactoferrin of the present invention promotes the proliferation of myoblasts at the initial stage of the process of muscle regeneration in the recovery and increase of muscle damage, and further promotes the differentiation of the grown myoblasts. It was shown that the change to myotube cells and the enlargement of the myotube cells were promoted, and the myofiber formation was clearly promoted.

<Examples of a lactoferrin-derived component-containing composition>
[Example 2 (pharmaceutical tablet)]
The powder preparation sufficiently mixed at the blending ratio shown in Table 2 was tablet-formed 500 mg at a time using a rotary tableting machine (VIRGO, manufactured by Kikusui Seisakusho) to produce lactoferrin-containing pharmaceutical tablets. Using the prepared tablet components, a myoblast promoting effect confirmation test was conducted, and the results are shown in Table 3.

乳糖：ダイラクトーズ（フロイント産業株式会社）
ラクトフェリン：森永ラクトフェリン ＭＬＦ−１（森永乳業株式会社）
グア−ガム： ビストップＤ−２０（三栄源エフ・エフ・アイ株式会社）
コーンスターチ：局方コーンスターチ（日本コーンスターチ株式会社）

Lactose: Dilactos (Freund Sangyo Co., Ltd.)
Lactoferrin: Morinaga lactoferrin MLF-1 (Morinaga Milk Industry Co., Ltd.)
Guar-Gum: Bistop D-20 (Saneigen FFI Co., Ltd.)
Corn Starch: Pharmacopoeia Corn Starch (Japan Corn Starch Co., Ltd.)

[Example 3 (pharmaceutical capsule)]
The preparation sufficiently mixed with the blending ratio shown in Table 4 was filled 200 mg each using a capsule filling machine (Matsuya KM-HS type, Matsuya Shoten) to prepare lactoferrin-containing pharmaceutical capsules.

アルファ化澱粉：マツノリンＭ（松谷化学工業）
ラクトフェリン：森永ラクトフェリン ＭＬＦ−１（森永乳業株式会社）

Pregelatinized starch: Matsunoline M (Matsutani Chemical Industry)
Lactoferrin: Morinaga lactoferrin MLF-1 (Morinaga Milk Industry Co., Ltd.)

[Example 4 (acid milk beverage)]
All ingredients other than the fragrance were mixed at the blending ratio shown in Table 5, homogenized (150 kg / cm 2), added with fragrance, stirred rapidly, then sterilized and filled (90 ° C., 10 minutes), lactoferrin-containing acid milk A beverage was prepared.

エリスリトール（三菱化学フーズ株式会社）
５０％乳酸（昭和化工株式会社）
ラクトフェリン：森永ラクトフェリン ＭＬＢ−１（森永乳業株式会社）
カラメル色素：カラメル ＬＦ−１４１（池田糖化工業株式会社）

Erythritol (Mitsubishi Chemical Foods Corporation)
50% lactic acid (Showa Kako Co., Ltd.)
Lactoferrin: Morinaga lactoferrin MLB-1 (Morinaga Milk Industry Co., Ltd.)
Caramel color: Caramel LF-141 (Ikeda Saccharification Co., Ltd.)

[Example 4 (jelly beverage)]
The raw materials are mixed at the blending ratio shown in Table 6, and stirred and dissolved at 80 ° C. for 10 minutes. Correct the total amount and fill the container. Sterilize at 85 ° C for 30 minutes.

砂糖：上白糖Ｊ（三井製糖株式会社）
ゲル化剤：伊那寒天ＵＰ−６（伊那食品工業株式会社）
ラクトフェリン：森永ラクトフェリン ＭＬＦ−１（森永乳業株式会社）
クエン酸三ナトリウム：精製クエン酸ナトリウムＳ（扶桑化学工業株式会社）

Sugar: Kami white sugar J (Mitsui Sugar Co., Ltd.)
Gelling agent: Inagar Agar UP-6 (Ina Food Industry Co., Ltd.)
Lactoferrin: Morinaga lactoferrin MLF-1 (Morinaga Milk Industry Co., Ltd.)
Trisodium citrate: Purified sodium citrate S (Fuso Chemical Co., Ltd.)

It has been reported that when a lactoferrin solution is orally administered to rats, 221.6 ng / ml of lactoferrin is detected in the blood 2 hours after administration of 0.1 g of lactoferrin per kg of body weight of the rat. In addition, even when humans ingest lactoferrin, there are reports of detecting lactoferrin in blood, and it has been clarified that lactoferrin is taken into blood in the body by ingestion. Regarding the uptake of lactoferrin in the body, the route from the intestinal tract to the lymphatic tract and uptake into the body has also been clarified (Reference Experimental Physiology page 263, 2004). Therefore, even when lactoferrin is orally ingested, it is effectively absorbed into the body and brings about an activity promoting effect of myoblasts and myotubes involved in muscle repair and enhancement.

  The present invention, by means of lactoferrin-derived components, actively promotes myoblast proliferation, differentiation, and myotube hypertrophy related to muscle repair and enhancement, and achieves shortening of the time to myofiber formation, In addition, since the risk of side effects is significantly reduced, it becomes possible to operate a healthy life without inconvenience in daily life, leading to an improvement in the quality of life. In addition, it is possible to provide a highly safe composition, which is considered to have high utility value in the pharmaceutical manufacturing and food manufacturing industries.

Claims (5)

  Composition for promoting myoblast proliferation / differentiation and myotube hypertrophy which contains a component derived from lactoferrin   The composition according to claim 1, wherein the composition is taken by oral administration, nasal administration, tube administration, or enteral administration.   3. Composition according to claim 1 or 2, characterized in that it is a medicament.   The composition according to claim 1, wherein the composition is a food.   The composition according to claim 1, wherein the composition is a supplement.

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