JP2013129612A - Medicine for sustaining feeling of fullness - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a satiety-satisfying agent that gives a sustained satiety.
A satiety-satisfying agent comprising polyglutamic acid or a salt thereof as an active ingredient.
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Description

  The present invention relates to a satiety-satisfying agent that can continuously give a feeling of fullness after ingestion.

  Obesity is the result of abnormal accumulation of energy sources such as carbohydrates and lipids as neutral fat in living tissue, especially white fat cells in the subcutaneous fat tissue and tissues around the organs, resulting in weight limitations in the skeletal system or physiological functions. It is in a state of increasing beyond. In particular, visceral adipose tissue is considered to cause abnormalities in carbohydrate metabolism and lipid metabolism, and may develop into lifestyle-related diseases such as heart disease, arteriosclerosis, hypertension, diabetes, and fatty liver. Therefore, in recent years, in order to reduce fat in the body, there is an interest in preventing dietary intake restrictions and excessive caloric intake.

  However, if food intake is restricted, it will hinder the feeling of hunger because the hunger sensation will always be sustained. It is effective to execute it. Conventionally, for example, a composition containing collagen and potato proteinase inhibitor II (Patent Document 1), an insoluble dietary fiber derived from a cereal plant seed (Patent Document 2), and the like have been reported as materials that maintain satiety.

  On the other hand, polyglutamic acid (PGA), which is a natural polymer obtained from the culture solution of Bacillus natto gum, is a biodegradable polymer and food thickener because of its high water absorption and water retention. Widely used as a moisturizer for cosmetics. Further, as its physiological action, calcium absorption promoting action (Patent Document 3), blood pressure increase inhibiting action (Patent Document 4) and the like are known.

  However, it is not known at all that polyglutamic acid and its salts give a feeling of continuous satiety.

JP 2010-1187 A JP2011-55A Japanese Patent Laid-Open No. 5-95767 JP 2008-255063 A

  The present invention relates to providing a satiety-sustaining agent that gives a feeling of continuous satiety.

  The present inventors have found that when polyglutamic acid (salt) is ingested by humans, a feeling of satiety occurs and the feeling of fullness lasts for a certain period of time, and polyglutamic acid or a salt thereof is useful as a satiety-sustaining agent. I found out.

That is, the present invention relates to the following 1) to 2).
1) A satiety-sustaining agent comprising polyglutamic acid or a salt thereof as an active ingredient.
2) The satiety maintaining agent of 1) above, wherein the polyglutamic acid is γ-polyglutamic acid.

  The satiety-satisfying agent of the present invention produces a feeling of satiety when ingested, and the feeling of satiety lasts for a certain period of time. Therefore, if the satiety-satisfying agent of the present invention is used, overeating can be avoided and it is useful for the prevention or improvement of obesity and lifestyle-related diseases. In addition, the use of the satiety-sustaining agent of the present invention makes it easier to perform a diet.

The graph which shows the awareness evaluation result of an appetite. ● indicates the control food intake group, and ○ indicates the PGA food intake group. AVG ± SE (N = 10), * p <0.05 vs control diet. The graph which shows a time-dependent change of a blood glucose level. ● indicates a control diet and ○ indicates a PGA diet. AVG ± SE (N = 10)

  In the present invention, “polyglutamic acid” is a polypeptide having glutamic acid as a polymerization unit, which may be either α or γ-polyglutamic acid, but γ in which a carboxyl group at the γ-position and an amino group at the α-position are peptide-bonded. -Polyglutamic acid (γ-PGA) is preferred. Further, the polyglutamic acid of the present invention may be any of D-form composed of D-glutamic acid, L-form composed of L-glutamic acid, and D- and L-form composed of D-glutamic acid and L-glutamic acid.

The molecular weight of polyglutamic acid is known from several thousands to several million, and in the present invention, any molecular weight can be used. Is preferably 3000 to 3 million, more preferably 5000 to 2 million, and even more preferably 10,000 to 1 million.
In addition, a crosslinked product obtained by further crosslinking polyglutamic acid to increase the molecular weight can also be used.

The polyglutamic acid of the present invention can be obtained from a known chemical synthesis method or a culture solution of Bacillus bacteria such as Bacillus natto.
Natural polyglutamic acid is a polymer in which glutamic acid is bound at the γ position, and as a microorganism that produces polyglutamic acid in the wild type, for example, some Bacillus bacteria and related species including Bacillus natto (Bacillus subtilis var. Chungkookjang, Bacillus icheniformis, Bacillus megaterium, Bacillus anthracis, Bacillus halodurans), Natrialba aegyptiaca, Hydra, etc. can be mentioned [Ashiuchi, M., et al .: Appl. Microbiol. Biotechnol., 59, pp.9-14 (2002)]. In addition, as an example of production of polyglutamic acid using a gene recombination technique, about 9 g / L / 5 days [Ashiuchi, M., et al.] In recombinant Bacillus subtilis (Bacillus subtilis ISW1214 strain) gene-transferred with a plasmid. .: Biosci. Biotechnol. Biochem., 70, pp. 1794-1797 (2006)], about 4 g / L / 1.5 days in recombinant Escherichia coli transfected with a plasmid [Jiang, H., et al .: Biotechnol. Lett., 28, pp.1241-1246 (2006)] is known to be obtained. Alternatively, polyglutamic acid is commercially produced as a food additive, cosmetic material, thickener, etc., and domestic and overseas polyglutamic acid manufacturers (Japan Polyglu, Ichimaru Falcos, Meiji Food Materia, BioLeaders, etc.) Can also purchase polyglutamic acid.

The polyglutamic acid used in the present invention may be a salt. In this case, examples of the salt include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, ammonium salt, ethanolamine salt, basic amino acid salt, etc. There is no particular limitation as long as it can be used as a use, but sodium salt and potassium salt are particularly preferable. Polyglutamic acid is insoluble in water, but becomes water-soluble when converted to a salt.
Such a salt of polyglutamic acid can be obtained by suspending the polyglutamic acid obtained above in water, neutralizing it with, for example, an aqueous solution of sodium hydroxide or potassium hydroxide, and freeze-drying the solution.

As shown in the examples below, polyglutamic acid or a salt thereof is satiety when ingested by humans, and the satiety persists for at least 4 hours after ingestion. At this time, the blood sugar level does not increase.
Therefore, the polyglutamic acid or a salt thereof of the present invention can be used for ingestion or administration to animals including humans to exert a feeling of continuous satiety for the purpose of preventing or ameliorating obesity or lifestyle-related diseases or dieting. It can be a feeling of satiety.

Here, the “feeling of fullness” refers to a sense in a situation where the user does not feel hungry, and particularly refers to a sense in a situation where the user does not want to eat a meal (the appetite is suppressed). Such a sensation is the Visual Analog Scale (VAS) method (Marleen MJW Kamphuis et.al. Am J Clin Nutr. 2003, 7, 133-1139, Holt SHet al., Eur J Clin Nutr. 1995, 9, 75-690) It is judged by a questionnaire like In particular, it is judged by the item of the degree of desire for meal.
In the present invention, “sustained feeling of fullness” means that the above feeling of fullness is sustained for at least 2 hours, preferably 3 hours or more, more preferably 4 hours or more.

The satiety-retaining agent may itself be a human or veterinary drug, quasi-drug, food or feed for sustaining satiety, or the drug, quasi-drug, food or feed. It may be a raw material or a preparation used in combination.
In addition, the food includes functional foods such as beauty foods, foods for the sick, or foods for specific health, which are based on the concept of sustaining a feeling of fullness or suppressing feelings of hunger, as necessary. .

Examples of the administration form of the above-mentioned pharmaceutical containing the polyglutamic acid or its salt of the present invention include oral administration or injection, such as tablets, capsules, granules, powders, syrups, enteric solvents, troches, drinks, and the like, sitting And parenteral administration by an agent, a transdermal absorption agent, an external preparation and the like.
In addition, the pharmaceutical preparations of such various dosage forms include the polyglutamic acid of the present invention or a salt thereof alone or other pharmaceutically acceptable excipients (such as sorbitol, glucose, lactose, dextrin, starch). Sugars, calcium carbonate and other inorganic substances, crystalline cellulose, distilled water, sesame oil, corn oil, olive oil, rapeseed oil, etc.), binders, lubricants, extenders, disintegrants, surfactants, lubricants, dispersants, suspensions Suspending agents, emulsifying agents, buffering agents, preservatives, flavoring agents, fragrances, coating agents, carriers, diluents, antioxidants, and the like can be prepared in appropriate combinations.
Among these dosage forms, the preferred form is oral administration, and the content of the polyglutamic acid of the present invention or the salt thereof in the preparation for oral administration is generally preferably 0.01 to 100% by mass, It is more preferable to set it as 0.1-80 mass%.

  Examples of the form of the food containing the polyglutamic acid or salt thereof according to the present invention include, for example, processed foods such as bread and noodles, rice processed foods such as rice cakes and cooked rice, biscuits, cakes, jelly, chocolate, Sweets such as rice crackers, ice cream, processed foods such as tofu, processed foods, soft drinks, fruit juices, milk drinks, carbonated drinks, dairy products such as yogurt, cheese, butter, milk, soy sauce, Examples include seasonings such as sauce, miso, mayonnaise, dressing, meat storage such as ham, bacon, sausage, processed meat food, marine processed food such as hampen, chikuwa, canned fish, cooking oil and frying oil. In addition, oral enteral nutritional foods such as capsules, concentrated liquid foods, natural liquid foods, semi-digested nutritional foods, ingredient nutritional foods, drink nutritional foods, etc. It is also possible to adopt a form such as

Examples of the feed include feed for small animals used for rabbits, rats, mice and the like, feed for pet foods used for dogs, cats, small birds, squirrels, and the like.
In various forms of food and feed, the polyglutamic acid or salt thereof of the present invention alone or other food materials, solvents, softeners, oils, emulsifiers, preservatives, fragrances, stabilizers, colorants, oxidation agents An inhibitor, a humectant, a thickener and the like can be appropriately combined for preparation. In general, the content of the polyglutamic acid of the present invention or a salt thereof in the food is preferably 0.01 to 100% by mass, and more preferably 0.1 to 80% by mass.

The intake / dose amount of the polyglutamic acid or salt thereof of the present invention in the above pharmaceutical, quasi-drug, food or feed is not particularly limited as long as the effect is obtained. In addition, the intake / dose may vary according to the subject's condition, weight, sex, age or other factors, but the daily dose or intake per adult (60 kg) may be As glutamic acid or a salt thereof, for example, it is preferably 1 to 20,000 mg, more preferably 5 to 5,000 mg, and particularly preferably 10 to 3,000 mg. The preparation can be ingested / administered according to an arbitrary ingestion / administration plan, but is preferably divided into once to several times a day and continuously ingested / administered for several weeks to several months.
In addition, when the satiety-sustaining agent is a food or medicine by itself, it can be used in association with food intake or as an alternative to food intake. In this case, before or after food intake or food intake By using it at the same time, food intake and calorie intake can be suppressed, which is preferable. When used before food intake, it is preferably used within 1 hour before food intake, more preferably within 30 minutes before food intake, and particularly preferably within 10 minutes. Moreover, when using after ingestion of food, it is preferable to use within 1 hour after ingestion of food, it is more preferable to use within 30 minutes after ingestion of food, and it is especially preferable to use within 10 minutes.

  In addition, the person who takes or administers the above-mentioned pharmaceutical, quasi-drug or food is not particularly limited as long as it is necessary, but humans and non-human mammals aiming at prevention or improvement of obesity and lifestyle-related diseases. An animal or a human who has restricted food intake for slimming the body is preferable.

Example 1 Sustained satiety effect of polyglutamic acid (1) Test article As polyglutamic acid (hereinafter referred to as PGA), “Meiji polyglutamic acid (Meiji Food Materia)” (γ-polyglutamic acid Na, average molecular weight 910,000) was used.

(2) Test meal Model breakfast (ham sandwich, yogurt, juice) (total calories: 450kcal, sugar 60%, fat 26%, protein 14%) 100g of barley tea (1.3g of polyglutamic acid dissolved) before ingestion Ingested. The test meal was prepared on the morning of the test day.

(3) Test outline Two groups of crossover tests were conducted in the same subject (healthy adult male). That is, the above-described control diet or a PGA diet loaded with PGA was eaten as breakfast, and appetite evaluation was performed over time until 4 hours later. Moreover, the appetite change over time after the meal between test meals was compared from the subjective evaluation of appetite.

1) Subject:
Ten healthy male adults.

2) Test procedure <Day before test>
At 7 pm, take the prescribed lunch (sugar / lipid / protein = 55/30/15%, 900 kcal) as dinner, and after that, snacking is prohibited, and consumption other than the prescribed drinking water (mineral water) is prohibited It was.
<Test day>
On the day, the prescribed drinking water was allowed until 7 am, and after that it was not allowed. On the day, smoking was prohibited until the end of the study.
In the test meal, barley tea with or without PGA was first drunk and then a model breakfast was taken. 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours after meals, a total of 5 times, appetite evaluation and blood sampling were performed over time.

3) Awareness assessment of appetite A questionnaire on appetite assessment by the VAS method (Visual Analog Scale) was created in order to have a self-evaluation of appetite after eating (feeling of hunger, satiety, amount to eat). Seven questionnaire items were set based on Marleen MJW Kamphuis et.al.Am J Clin Nutr.2003,7,133-1139, Holt SHet al., Eur J Clin Nutr.1995,9,75-690.

i) Hunger feeling: hunger
ii) Stomach satisfaction: fullness
iii) Appetite: appetite
iv) Fullness: satiety
v) Thirsty: thirst
vi) The next meal: estimate of prospective food intake
vii) Desire for eating: desire to eat

A 100mm straight line was drawn on the questionnaire, and both ends were set as the counter electrode of the above seven items. Subjects were asked to mark the position closest to the current state on this straight line, and the length from the left end to the marked position (in mm) was measured with a ruler to quantify appetite.
The obtained numerical value (VAS value) is shown by mean ± standard error, and the significant difference test between test meals was performed by a paired t-test, with P <0.1 as the significance level.

4) The blood glucose level of the collected blood was immediately measured with a simple blood glucose meter (Roche Dagnostics, ACCU-CHEK).

(4) Test results i) VAS values obtained from questionnaires vary in the index of satiety and hunger between individuals, so that the minimum and maximum appetite assessments are adjusted to 0-100. Went. FIG. 1 shows the change over time of the post-meal increase in the VAS value in each item after correction.
As shown in FIG. 1, the appetite after the meal was decreased in the PGA diet as compared with the control diet for any item. In particular, the appetite at 4 hours after meal was significantly lower in the PGA diet group for “degree of appetite”, and the appetite at 2, 3, and 4 hours after meal was significantly lower in the PGA diet group. Significantly low, suggesting the possibility of sustained satiety by taking PGA.
ii) Moreover, the time-dependent change of the blood glucose level after a meal is shown in FIG.
There was no significant difference in blood glucose levels between the control diet and the PGA diet.

Claims (2)

  A satiety-retaining agent comprising polyglutamic acid or a salt thereof as an active ingredient.   The satiety-sustaining agent according to claim 1, wherein the polyglutamic acid is γ-polyglutamic acid.

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