JP5100033B2 - Gastrointestinal and renal atrophy inhibitor - Google Patents

Description

  The present invention relates to a preparation containing a branched chain amino acid for suppressing atrophy of the digestive tract and kidneys.

  Weight loss or dietary restriction may be accompanied by atrophy of the gastrointestinal tract tissue, and it has been pointed out that this atrophy may lead to a gastrointestinal tract disease due to a decrease in gastrointestinal immunity and the manifestation of past illnesses such as ulcers. Thus, there is a need for pharmaceutical compositions and foods that allow weight loss without causing atrophy of the digestive tract and kidneys.

  The main object of the present invention is to provide a preparation containing a branched chain amino acid that suppresses atrophy of the digestive tract and kidneys at the time of weight reduction, a pharmaceutical composition containing the preparation, and a food.

The inventors of the present invention have made extensive studies to solve the above problems, and can reduce the amount efficiently without causing atrophy of the gastrointestinal tract and kidneys associated with weight loss if it is a preparation containing a branched chain amino acid. I found it possible. The present invention has been completed as a result of further research based on such knowledge. The present invention provides the following preparations, pharmaceutical compositions and foods.
Item 1. An agent for suppressing atrophy of the digestive tract and kidney accompanying weight loss, comprising at least one branched chain amino acid selected from the group consisting of leucine, isoleucine and valine.
Item 2. Item 2. The atrophy inhibitor according to Item 1, comprising at least leucine.
Item 3. Item 4. The atrophy inhibitor according to Item 1, comprising leucine, isoleucine and valine.
Item 4. A pharmaceutical composition comprising the digestive tract and kidney atrophy inhibitor accompanying weight loss described in Item 1.
Item 5. Item 5. The pharmaceutical composition according to Item 4, which has a parenteral dosage form.
Item 6. Food containing the digestive tract and kidney atrophy inhibitor accompanying weight loss described in Item 1.
Item 7. Item 7. The food according to Item 6, which is a beverage form.
Item 8. Item 7. The food according to Item 6, which is granular.

  According to the present invention, atrophy of the digestive tract and kidneys due to weight loss can be suppressed. Therefore, according to the present invention, it is possible to reduce the amount efficiently and healthily. Moreover, not only at the time of weight loss but also in a person who tends to be deficient in nutrition intake due to hospitalization or bedridden, it can be expected to suppress the decrease in muscle mass while suppressing atrophy of the digestive tract and kidneys.

  In the present invention, “atrophy of the digestive tract and kidney” refers to the following phenomenon. That is, the digestive tract atrophy means that the cells constituting the digestive tract wall become smaller, the digestive tract wall becomes thinner, and the weight decreases. When the digestive tract wall becomes thin, for example, bacteria existing in the intestinal tract are likely to enter the body, or digestion and absorption are not expected to be successful. In addition, kidney atrophy means that the cells constituting the kidney become smaller and the weight of the kidney decreases. Atrophy of the kidney is thought to cause a decrease in kidney function such as inability to excrete waste and excess water in the body.

Hereinafter, the preparation, pharmaceutical composition and food and drink of the present invention will be described.
(1) Gastrointestinal and renal atrophy inhibitor accompanying weight loss The present invention is characterized by containing at least one branched-chain amino acid (BCAA). In the present invention, a branched chain amino acid is an essential amino acid having a branched chain, and includes three types of leucine, isoleucine and valine. In the present invention, it is preferable to contain at least leucine, and when it contains two or more kinds of branched chain amino acids, it is desirable to contain leucine and isoleucine and / or valine. The digestive tract and kidney atrophy inhibitor of the present invention preferably contains three kinds of branched chain amino acids of leucine, isoleucine and valine. When the atrophy-suppressing agent of the present invention contains at least leucine and at least one of the other two amino acids is used, each blending ratio is 0.1 parts by weight when leucine is 1 part by weight. About 1 to 1 part by weight, preferably about 0.2 to 0.8 part by weight; valine about 0.1 to 1 part by weight, preferably about 0.1 to 0.8 part by weight, preferably 0.2 to 0. About 8 parts by weight.

  The above-mentioned branched chain amino acids can be used as a raw material, and are not particularly limited. For example, free form pure crystalline amino acids, pharmacology such as sodium salt, potassium salt, hydrochloride, acetate, etc. It may be in the form of an acceptable salt. In addition, the above three types of amino acids can be used in the form of dipeptides or tripeptides. When used in the form of dipeptides or tripeptides, these peptides can be effectively utilized by being hydrolyzed into free amino acids by the action of peptidases present in the living body.

  In addition, the agent for inhibiting atrophy of the digestive tract and kidneys accompanying weight loss of the present invention is pharmaceutically or food hygienically acceptable in addition to the above branched chain amino acids, as long as the effects of the present invention are not impaired. Conventionally known additives such as amino acids, stabilizers, preservatives, solubilizers, pH adjusters, thickeners, antioxidants, colorants, fragrances and artificial sweeteners may be blended as necessary. it can. The blending amount of these additives can be appropriately set according to the blending amount of the branched chain amino acid.

The digestive tract and kidney atrophy inhibitor of the present invention is used as an active ingredient of a pharmaceutical composition.

(2) Pharmaceutical composition In accordance with a conventionally known method, a pharmaceutical composition together with conventionally known pharmaceutically acceptable carriers, diluents, excipients, etc., containing the above-mentioned agent for inhibiting atrophy of the digestive tract and kidney accompanying weight loss as an active ingredient It can be prepared in the form of a product.

  The pharmaceutical composition of the present invention can be prepared in various pharmaceutical dosage forms, whether orally or parenterally, but is preferably a parenteral formulation. Examples of the dosage form of the pharmaceutical composition of the present invention include liquid preparations (including syrups), drops, injections and other liquid preparations; tablets, pills, powders, granules, capsules (including soft capsules), etc. The solid preparation is preferably an instillation or an injection.

  When the pharmaceutical composition of the present invention is a liquid preparation, it can be stored frozen, or it may be stored after removing moisture by lyophilization or the like. Freeze-dried preparations, dry syrups and the like are used by dissolving again by adding distilled water for injection, sterilized water or the like at the time of use.

  For example, when the pharmaceutical compositions of the present invention are prepared as injections, infusions, etc., they are preferably sterilized and isotonic with blood. When preparing such a dosage form, for example, water, ethyl alcohol, macrogol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitan fatty acid esters, etc. should be used as diluents. Can do. In this case, the pharmaceutical composition of the present invention may contain a sufficient amount of sodium chloride, glucose or glycerin to adjust a solution that is isotonic with the body fluid. Moreover, you may add the solubilizing agent, buffering agent, soothing agent, etc. which are generally used in this field | area. Furthermore, the digestive tract and kidney atrophy inhibitor of the present invention can be blended together with conventionally known drugs, infusions for tube feeding, infusions for intravenous administration, and the like to prepare the pharmaceutical composition of the present invention.

  Moreover, when preparing the pharmaceutical composition of the present invention as a solid preparation, for example, in the case of a tablet, various carriers well known in the art can be widely used as carriers. Examples thereof include excipients such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid, water, ethanol, propanol, simple syrup, glucose solution, starch solution, Binders such as gelatin solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone, dry starch, sodium alginate, agar powder, laminaran powder, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, lauryl sulfate Disintegrators such as sodium, stearic acid monoglyceride, starch, lactose, disintegration inhibitors such as sucrose, stearin, cocoa butter, hydrogenated oil, absorption accelerators such as quaternary ammonium base, sodium lauryl sulfate, glyce Emissions, moisturizing agents such as starch, starch, lactose, kaolin, bentonite, adsorbent such as colloidal silicic acid, purified talc, stearates, boric acid powder, a lubricant such as polyethylene glycol can be used. Further, the tablets can be made into tablets with ordinary coatings as necessary, for example, sugar-coated tablets, gelatin-encapsulated tablets, enteric-coated tablets, film-coated tablets, double tablets, and multilayer tablets.

  Moreover, when preparing in the form of a pill, a conventionally well-known thing can be widely used as a support | carrier in this field | area. Examples include excipients such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, kaolin and talc, binders such as gum arabic powder, tragacanth powder, gelatin, ethanol, and disintegrants such as laminaran and agar. Can be used.

  In addition to the above, additives include, for example, binders, surfactants, absorption promoters, humectants, adsorbents, lubricants, fillers, extenders, moisturizers, preservatives, stabilizers, emulsifiers, A solubilizer and a salt for adjusting osmotic pressure can be appropriately selected and used depending on the dosage unit form of the resulting preparation. Moreover, you may contain other active ingredients (for example, vitamins, inorganic salts, etc.). Furthermore, you may use in combination with another medicinal component. Moreover, in the pharmaceutical composition of this invention, a coloring agent, a preservative, a fragrance | flavor, a flavoring agent, a sweetening agent, etc. can also be mix | blended and prepared as needed.

  If the pharmaceutical composition of the present invention is a liquid preparation, the total amount of branched chain amino acids in the pharmaceutical composition is about 0.01 to 10% by weight, about 0.05 to 5% by weight, preferably 0. About 1 to 2% by weight, more preferably about 0.2 to 1.2% by weight, and still more preferably about 0.3 to 1% by weight. The content of leucine in the liquid preparation of the present invention is about 0.1 to 1.5% by weight, preferably about 0.15 to 1.0% by weight, more preferably about 0.2 to 0.8% by weight. is there.

  When the pharmaceutical composition of the present invention is prepared as a solid preparation, the total amount of branched chain amino acids is about 10 to 80% by weight, about 20 to 80% by weight, preferably about 30 to 70% by weight, more preferably 30 It is desirable to contain about -60% by weight, more preferably about 30-58% by weight. The content of leucine in the solid preparation of the present invention is about 10 to 60% by weight, preferably about 10 to 50% by weight, more preferably about 15 to 45% by weight.

  The dosage of the preparation of the present invention is about 1.5 to 15 g, preferably about 2 to 8 g, more preferably about 3 to 5 g per adult per day in terms of branched chain amino acid. With such a dose, the effects of the present invention can be effectively exhibited.

  Examples of the food of the present invention include supplements, nutritional functional foods, foods for specified health use, foods for the sick, and the like. Examples of the form of the food of the present invention include forms such as powders, granules, capsules, tablets (including chewables), edible films, beverages (drinks), and the like, preferably granules or beverages. A preferred embodiment of the food of the present invention is a supplement having a granular form. The method for producing these foods is not particularly limited as long as the effects of the present invention are not impaired, and may follow a method used by those skilled in the art for each application.

  When the food of the present invention is produced in the form of granules, it is not particularly limited, but the particle size is desirably about 20 to 2000 μm, preferably about 100 to 1500 μm, more preferably about 500 to 1000 μm. The granular food of the present invention can be taken in a granular state together with beverages such as water, tea and juice, and can also be taken by dissolving in a beverage.

  For example, if the food of the present invention is a beverage, the total amount of branched chain amino acids in the food of the present invention is about 0.01 to 10% by weight, preferably about 0.05 to 5% by weight, preferably 0.1. It is desirable to contain about ˜2% by weight, more preferably about 0.2 to 1.2% by weight, and still more preferably about 0.3 to 1% by weight. The content of leucine in the food having the beverage form of the present invention is about 0.1 to 1.5% by weight, preferably about 0.15 to 1.0% by weight, more preferably 0.2 to 0.8% by weight. %.

  When the food of the present invention is a granule, the total amount of branched chain amino acids is about 10 to 80% by weight, about 20 to 80% by weight, preferably about 30 to 70% by weight, more preferably 30 to 60% by weight. It is desirable to contain about 30% by weight, more preferably about 30 to 58% by weight. The content of leucine in the food having the granular form of the present invention is about 10 to 60% by weight, preferably about 10 to 50% by weight, more preferably about 15 to 45% by weight. When preparing as a food having a form other than the above, the amount of branched chain amino acid can be appropriately set with reference to the amount of the food in the food.

  The daily intake of the food of the present invention is not particularly limited as long as the effects of the present invention are exhibited, and can be appropriately adjusted according to the dose of the branched chain amino acid.

  The pharmaceutical composition and food and drink of the present invention can suppress atrophy of the gastrointestinal tract and kidneys accompanying weight loss and the like by applying it to a person who is imposed weight loss or dietary restrictions. In addition, the pharmaceutical composition and food and drink of the present invention can suppress atrophy of the gastrointestinal tract and kidneys caused by a decrease in nutritional supplementation as well as at the time of weight reduction. The present invention can be preferably applied to other people.

  Hereinafter, the present invention will be described in more detail with reference to test examples and formulation examples, but the present invention is not limited thereto.

Test Example 1
SD male rats (6 weeks old) were allowed to perform a climbing exercise for 5 weeks. The conditions for the climbing exercise were 6 days a week, 15 minutes x 3 sets, which were gradually increased with the improvement of exercise ability. Thereafter, the amount of food was restricted so that the body weight decreased by about 4% in 16 days (weight loss period). The climbing exercise described above was continued during the weight loss period.

The above test was conducted for the following three groups (each n = 5).
(A) High protein diet group (HP group): Feeding a feed obtained by replacing part of the carbohydrate of the feed given to the control group with casein.
(B) High BCAA diet group (HB group): Feeding a feed obtained by substituting a part of the carbohydrate of the feed given to the control group with BCAA (valine, leucine and isoleucine).
(C) Feeding the control diet group (Control group): AIN-93G (manufacturer: Japan Claire)

  During the above test, the body weight (FIG. 1) and food intake (FIG. 2) of the rats were continuously measured. In addition, tissue weight was measured on the last day of the test. The tissues whose weights were measured are stomach, small intestine, large intestine and kidney.

  As a result, the body weight decreased by about 4% in each test group after 16 days of weight loss. The total tissue weight (gastrointestinal tract weight) of the stomach, small intestine, and large intestine after weight reduction was significantly larger in the HB group than in the Control group (shown as a in FIG. 3), but the HP group was different from the HB group and the Control group. There was no significant difference between them (shown as ab in FIG. 3). Moreover, the kidney weight was significantly larger in the HP group and the HB group than in the Control group (indicated by b in FIG. 4).

  For the groups that did not lose weight (groups that did not restrict food and exercise), the kidney weight and gastrointestinal weight were measured in the same manner as other groups, and the results were as shown in Table 2 below. Obtained.

  As shown in Table 2 above, the gastrointestinal weight of the HB group was reduced compared to the Control group that did not lose weight, but the gastrointestinal weight was reduced compared to the Control group and HP group that performed weight reduction. Tended to be suppressed. That is, it was suggested that by adding BCAA to the diet at the time of weight reduction, atrophy of the digestive tract due to weight loss is suppressed. In addition, the kidney weight of the control group rats that did not lose weight was the same as that of the HP group and the HB group, whereas the kidney weight of the control group (with weight reduction) was decreased. Therefore, in the HP group and the HB group, it is considered that kidney atrophy due to weight loss was suppressed.

Formulation Example Granules were prepared according to a conventional method using the ingredients shown in Table 3 below in a granulator.

It is a graph showing the body weight change of each group rat during a test period. It is a graph showing the change of the food intake of each group rat during a test period. It is a graph which shows the total tissue weight of the stomach, the small intestine, and the large intestine after weight reduction in each group. It is a graph which shows the kidney weight after the weight loss in each group.

Claims (3)

Leucine, and containing not isoleucine and valine, for oral, gastrointestinal under reduced or nutrition restrictions and atrophy pharmaceutical composition for inhibiting the kidneys. The pharmaceutical composition according to claim 1, which is used for prevention or improvement of intestinal bacterial infection, digestion malabsorption or decrease in renal function. For the manufacture of oral pharmaceutical compositions with atrophy inhibition of the digestive tract and kidney under reduced or nutrient intake restriction, leucine, use of isoleucine and valine.

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