JP4772295B2 - Exercise capacity improver containing conjugated fatty acid as an active ingredient - Google Patents

Description

  The present invention relates to an agent for improving athletic ability or blood property, comprising a conjugated fatty acid as an active ingredient. More specifically, the present invention relates to a decrease in blood viscosity, a decrease in blood lactate concentration, or an intramuscular enzyme in blood. For those who perform aerobic exercise that requires endurance represented by long-term exercise, such as long-distance running, or those who are strenuously exercising muscular labor, or animals by improving blood properties such as deviation control Further, the present invention relates to an agent for improving athletic ability or blood property for the purpose of improving muscle fatigue or endurance.

  In the present day when life is irregular, it is important to exercise moderately as a hobby or to maintain health and prevent lifestyle-related diseases. In 2000, the Ministry of Health and Welfare (now the Ministry of Health, Labor and Welfare) will present goals and other objectives for FY2010 on issues that are important for national health insurance measures such as lifestyle-related diseases and lifestyle-related diseases. "National Health Promotion Movement in the Century (Health Japan 21)"

  In such a current situation, although the importance of exercise is increasing, the number of people who are exercising such as consciously moving their bodies in order to maintain and improve their health is not increasing. Also, for those who are exercising habitually, it is not difficult to continue exercising, but for those who are not habitually exercising, it is easy to get tired even after exercising, and moreover endurance It is difficult to keep exercising continuously.

  In addition, when intense exercise or labor is performed, glycogen-derived glucose in muscle is used, and an anaerobic glycolysis reaction proceeds to synthesize ATP necessary for muscle contraction. And it is thought that lactic acid which is the metabolite accumulates and the pH in the muscle is lowered, the efficiency of muscle contraction is lowered, resulting in muscle fatigue.

In recent years, several substances have been reported as materials that are expected to improve athletic ability and anti-fatigue effects, and have been proposed for use as foods.
Creatine: Harris, RC et al., Clin. Sci., 83, 367-374, 1992
Amino acid composition: Amino acid composition constructed according to amino acids contained in saliva secreted by hornets larvae (Japanese Patent Laid-Open No. 9-249556)
-Imidazole dipeptides: JP 2002-173442-Hawthorn extract: JP 9-266767-Ganoderma component: JP 5-123135-Coenzyme Q10 and hydroxycitric acids: JP 2004-81010 Publication: n-3 polyunsaturated fatty acids: JP-A-11-239465
Japanese Patent Laid-Open No. 9-249556 JP 2002-173442 A JP-A-9-266767 JP-A-5-123135 JP 2004-81010 A JP-A-11-239465 Harris, RC et al., Clin. Sci., 83, 367-374, 1992

  An object of the present invention is to provide an improving agent that can lead to improvement of athletic ability, such as improvement of muscle fatigue or endurance, and a food, beverage, feed, health supplement and medicine using the same. is there.

  As a result of intensive studies to achieve the above-mentioned object, the present inventors have found that blood properties such as conjugated fatty acids such as conjugated linoleic acid have decreased blood viscosity, decreased blood lactic acid concentration, or inhibited intramuscular enzyme escape into blood. It has been found that there is an action of improving the ability of the body, and that this can lead to the action of an athletic ability improving agent such as improvement of muscle fatigue or endurance in exercise, and the present invention has been completed based on this finding.

That is, the gist of the present invention is as follows.
(1) A motor performance improving agent or a blood property improving agent comprising a conjugated fatty acid as an active ingredient.
(2) The improvement of exercise capacity is improvement of muscle fatigue due to exercise or improvement of endurance in exercise, and the improvement of blood properties is a reduction in blood viscosity, blood lactate concentration or inhibition of intramuscular enzyme escape into blood. The improving agent according to (1), wherein
(3) The improving agent according to (1) or (2) above, wherein the conjugated fatty acid is in a form selected from a free fatty acid, a salt thereof, an ester, a fatty acid derivative, or a mixture of two or more thereof.
(4) The ester of the fatty acid is an ester of the fatty acid and one or more alcohols selected from the group consisting of an alcohol having 1 to 10 carbon atoms, ethylene glycol, propylene glycol, and glycerin. The improving agent according to any one of (1) to (3) above.
(5) The above (1) to (4), wherein the metal salt of the fatty acid is one or two or more salts selected from the group consisting of sodium salts, potassium salts, calcium salts, zinc salts and magnesium salts. The improvement agent in any one of.
(6) The improving agent according to any one of (1) to (5), wherein the conjugated fatty acid is conjugated linoleic acid.
(7) A food / beverage product comprising the conjugated fatty acid described in any one of (1) to (6) above and having an effect of improving exercise capacity or improving blood properties. Or the food-drinks containing the conjugated fatty acid as described in any one of said (1)-(6) used for exercise ability improvement or blood property improvement.
(8) The athletic ability improving or blood property improving agent according to any one of (1) to (6), which is used as a health supplement.
(9) The athletic ability improving or blood property improving agent according to any one of (1) to (6), which is used as a pharmaceutical product. That is, an agent for improving exercise capacity or improving blood properties, comprising the conjugated fatty acid described in any of (1) to (6) above.
(10) The athletic ability improving or blood property improving agent according to any one of (1) to (6), which is used as a feed.

According to the present invention, improvement in blood properties such as blood viscosity reduction, blood lactate concentration reduction or inhibition of intramuscular enzyme escape into blood by ingestion of an improvement in exercise ability or blood property improvement agent containing conjugated fatty acid as an active ingredient. In those who perform aerobic exercise that requires endurance, such as long-distance exercise such as long distance running, or who work or work hard in muscles or animals, Exercise ability such as improvement of endurance in exercise can be improved.
It is understood that it is unexpected that conjugated fatty acids can have an effect of improving the blood properties as described above, and thus an effect of improving exercising ability such as improvement of muscle fatigue or endurance in exercise.

  The improving agent according to the present invention is an athletic performance improving agent, specifically, an agent for improving muscle fatigue due to exercise or an endurance for exercise, and in another aspect, an agent for improving blood properties, specifically, It is also a blood viscosity (or hemorheology) reducing agent, a blood lactate concentration reducing agent, or a deviating inhibitor of intramuscular enzymes (lactate dehydrogenase, creatine kinase, etc.) into blood (Examples described later and FIGS. 1 to 5) reference).

  The conjugated fatty acid as an active ingredient in the improver of the present invention is used in the form of a free fatty acid, salt, ester, fatty acid derivative or a mixture of two or more thereof.

  The ester is one selected from the group consisting of conjugated fatty acids and alcohols having 1 to 38 carbon atoms, preferably 1 to 10 alcohols (for example, aliphatic alcohols and higher alcohols), ethylene glycol, propylene glycol and glycerin. Alternatively, an ester with two or more alcohols is preferable, and other polyglycerols (for example, di- to tetra-glycerol), sterols (for example, β-sterol), saccharides (monosaccharides, disaccharides, oligosaccharides (for example, tri to Decasaccharide)), polysaccharides (for example, degree of polymerization 11 to 30), esters with ascorbic acid and the like.

  The fatty acid salt is one or two selected from the group consisting of sodium salt, potassium salt, calcium salt, zinc salt, magnesium salt, ammonium salt, sodium carbonate salt, magnesium chloride salt, double salt, complex salt and the like. Examples include salts such as metal salts of more than species.

  Furthermore, the conjugated fatty acid used in the present invention is in the form of any other pharmacologically acceptable fatty acid derivative such as amide or phospholipid in addition to the above-mentioned salt form such as ester or metal salt. May be.

  Hereinafter, the present invention will be described more specifically based on preferred embodiments.

  The conjugated fatty acid used in the present invention is preferably one or a plurality of conjugated fatty acids having 18 to 22 carbon atoms, and a typical example of the conjugated fatty acid is conjugated linoleic acid. As the conjugated linoleic acid, an equivalent mixture of 9cis, 11trans-isomer and 10trans, 12cis-isomer, which are the main isomers, may be used, but if necessary, the content of one isomer may be adjusted. High conjugated linoleic acid can also be used. The conjugated fatty acid is usually obtained in the form of a conjugated fatty acid-containing fatty acid using a known alkali coupling reaction with a raw material such as an oil or fat containing an unsaturated fatty acid (having two or more double bonds). The content of the conjugated fatty acid in the conjugated fatty acid-containing fatty acid is preferably 50% by weight or more, more preferably 60% by weight or more.

  Specific examples of conjugated linoleic acid include linoleic acid-containing fats and oils (for example, safflower oil and sunflower oil) or high-purity linoleic acid (for example, Tokyo Chemical Industry Co., Ltd. (98 wt% linoleic acid)) as a raw material. It was obtained by a method of converting linoleic acid to conjugated linoleic acid by subjecting it to an alkali conjugation reaction.

  The alkali conjugation reaction is a reaction in which a fatty acid is conjugated and converted into a conjugated fatty acid in an alkali-organic solvent liquid, and a known method can be used. For example, potassium hydroxide as an alkali and ethylene glycol as an organic solvent are typically used (Abstracts of the 34th Oil Chemistry Conference, p171 (1995), Standard Oil Analysis Test Method 2.4.16-17) Further, as a more preferable method, there is known a method with improved conjugation rate using propylene glycol as an organic solvent (Japanese Patent No. 3017108), and the like can be carried out using these known methods. Practically, a mixture of 9cis, 11trans- and 10trans, 12cis-conjugated linoleic acid is commercially available (for example, CLA-80 (manufactured by Linol Oil Co., Ltd.): 9cis, 11trans-conjugated linoleic acid 33.1%, 10trans , 12cis-conjugated linoleic acid 33.9%, the remaining conjugated linoleic acid: 4%, non-conjugated fatty acid: 29%), which can be used. It may also be a mixture of fatty acids obtained from conjugated linoleic acid-containing fats and oils produced by microorganisms (for example, lactic acid bacteria) (see, for example, US Pat. No. 6,060,304 using lactic acid bacteria).

  The conjugated linoleic acid content in the conjugated linoleic acid-containing fatty acid obtained by the method as described above is generally 5 to 95%, practically 50 to 85%, preferably 60 to 85%, and the remaining components Is a non-conjugated fatty acid. In addition, the content of both 9cis, 11trans- and 10trans, 12cis-isomers in the conjugated linoleic acid-containing fatty acid obtained as described above occupies most of the conjugated linoleic acid (of other conjugated linoleic acid isomers). The content is usually about 4 to 5%), and the mutual contents of both isomers are almost equal.

Also, in order to obtain fatty acids with an increased content of one of the two isomers (fatty acids having different contents of both isomers), a method of preferentially esterifying 9cis, 11trans-conjugated linoleic acid is known. . For example, a method of subjecting conjugated linoleic acid to 9cis, 11trans isomer selective esterification using lipase derived from Candida rugosa and alcohol (lauryl alcohol), followed by molecular distillation, enzymatic reaction, and urea addition (Nagao et al., JAOCS , 79, 303-308, 2002).

  The molecular distillation can be performed using, for example, conditions of 120 to 190 ° C. and 0.5 to 0.05 mmHg. In the enzyme reaction, the method using the lipase may be repeated one or more times as necessary. The reaction conditions can be arbitrarily set. For example, the enzyme is used at a concentration of 4 to 250 U / g for the reaction mixture (conjugated linoleic acid-containing fatty acid / lauryl alcohol mixture obtained by alkali conjugation). The reaction can be carried out at 30 ° C. for about 16 hours. The urea inclusion can be performed, for example, by adding 5-fold amount methanol and 1-fold amount urea to the fractionated liquid after molecular distillation and heating to 60 ° C.

  In the above method, a conjugated fatty acid-containing fatty acid in which the content of 9cis, 11trans-conjugated linoleic acid or 10trans, 12cis-conjugated linoleic acid is changed as desired by conveniently adjusting conditions such as enzyme concentration, reaction temperature, reaction time, etc. Can be obtained. The 9cis, 11trans-conjugated linoleic acid content or 10trans, 12cis-conjugated linoleic acid content in the conjugated linoleic acid-containing fatty acid obtained by the above method is 5% by weight or more, preferably 40% by weight or more, more preferably 85% by weight. Or more (for example, about 90%). In this case, the remaining components in the conjugated fatty acid-containing fatty acid are other isomers (9cis, 11cis / 10cis, 12cis mixed type, 9trans, 11trans / 10trans, 12trans mixed type), other non-conjugated fatty acids, oleic acid, etc. .

  9cis, 11trans-conjugated linoleic acid-containing fatty acid or 10trans by using chromatography (for example, high performance liquid chromatography using a silver ion column (US Pat. No. 6,153,774) etc.) instead of the above selective esterification method , 12cis-conjugated linoleic acid-containing fatty acid can be separated and fractionated to obtain conjugated linoleic acid having a high content of any isomer.

  As shown in the animal experiments of Examples described later, conjugated fatty acids have an effect of improving blood properties (blood viscosity reduction, blood lactate concentration reduction, inhibition of intramuscular enzyme escape into blood, etc.) It has been confirmed that it can lead to improvement of exercise capacity (improvement of muscle fatigue by exercise or improvement of endurance in exercise, etc.). Therefore, in the present invention, the conjugated fatty acid as described above (conjugated linoleic acid in a preferred embodiment) can be used as an agent for improving blood properties or improving exercise ability. The present invention relates to a food for improving blood properties or improving exercise capacity (including foods and drinks, health supplements, and feeds), and a medicament for improving blood properties or improving exercise capacity, comprising the conjugated fatty acid as described above as an active ingredient. Also related.

  One form of the food-drinks by this invention contains a conjugated fatty acid, and the form of fats and oils products (fatty acid, glyceride) is preferable. As the fatty acid form, the conjugated fatty acid obtained as described above can be used, and as the glyceride form, the fatty acid and glycerin obtained as described above are esterified using lipase by a usual method. Can be used. In the present invention, the conjugated fatty acid may be in the form of other various esters, salts such as metal salts, other pharmacologically acceptable derivatives, or a mixture thereof as described above. is there.

  In addition, the food and drink using the agent for improving athletic performance or blood property according to the present invention can be used in the form of a conjugated fatty acid-containing oil or fat product as exemplified above, and an edible oil or fat composition (vegetable oil or fat, animal Food and fat, processed oils and fats, edible emulsified oils and fats composition (margarine, mayonnaise, etc.), bakery products (bread, cakes, etc.), cooked foods (lunch, side dishes, etc.), beverages (juices, soft drinks, etc.) You may mix and use. As a health supplement, it can be used in the form of a soft capsule, a tablet or the like. Moreover, as a feed, it can be used with forms, such as addition to a mixing | blending feed. In the present invention, when blended with other general foods, the motor ability improving or blood property improving agent in foods is usually about 0.5 to 20% by weight, preferably 1 to 10% by weight as the amount of conjugated fatty acid. Ingestion of 1 mg to 10 g per day, preferably about 0.1 g to 10 g per day, is expected to improve exercise capacity or blood properties.

  When the motor performance improving agent or blood property improving agent of the present invention is used as a pharmaceutical product, its form is not particularly limited, and an injection solution depends on conditions such as the administration method, applied therapeutic purpose, shape, and site of presence. Various forms such as tablets, capsules, powders, granules, and drinks can be appropriately selected. Therefore, the above-described athletic ability improving agent or blood property improving agent of the present invention can be used as a medicine as it is, and various conventional additives such as carriers, diluents or excipients (eg, sugars, In combination with starches, alcohols, gum arabic, etc.) to give the desired pharmaceutical form. The dose of the agent for improving athletic ability or blood property improving agent of the present invention is a therapeutically effective amount and cannot be generally described depending on the purpose of treatment, etc., but generally for an adult with a body weight of 60 kg, the amount of the conjugated fatty acid per day is 10 Although it is -5000 mg, Preferably it is 20-3000 mg, It can also use together with the other therapeutic agent containing a well-known motor ability improvement or blood property improvement agent.

  In the present specification, “%” means “% by weight” unless otherwise specified, or unless clearly indicated only by “%”.

  The present invention will be described more specifically with reference to the following examples, but the present invention is not limited to these examples.

[Example 1]
SD male rats (body weight: about 170 g) were prepared by CLA (CLA-80HG (manufactured by Linoleum Oil & Fats Co., Ltd .; manufactured by Patent No. 3017108), conjugated linoleic acid content: 80.5%, ratio of each isomer: 9 cis, 11trans-conjugated linoleic acid 37.0%, 10trans, 12cis-conjugated linoleic acid 38.4%), other conjugated linoleic acid 5%, other fatty acids 19.6%)) added 1% soybean oil (unsaturated fatty acids such as linoleic acid) (Including) the containing diet was fed for 3 weeks (in addition, the outline of the preparation method of CLA is mentioned later). For the exercise load, a free-running exercise using a tread wheel was adopted. The diet composition used MF feed for mice and rats manufactured by Oriental Yeast Co., Ltd., the control group was 6% soybean oil, the CLA group was soybean oil 5%, and CLA 1%.
As a result, when the whole blood transit time was measured using a cell microrheology measuring machine, blood hemorheology increased viscosity when loaded with running exercise torening, but the increase in viscosity was weak in the CLA intake group, and control The value was lower than that of the soybean oil-containing feed (about 70%) (FIG. 1). Therefore, the blood is smooth, and it is presumed that the supply of nutrients and oxygen and the removal of fatigue substances are also performed quickly. In addition, the blood lactate concentration of the running exercise training load rat group showed a low value (about 75% with respect to the control) in the CLA intake group (FIG. 2). For this reason, in terms of energy to support exercise, CLA intake keeps the blood smooth, facilitates the supply of energy sources to muscles, and rapidly inhibits energy production enzyme reaction inhibitors (such as lactic acid) from muscles. It is thought that muscle fatigue is improved by the enhancement of fullness of muscle power.
In addition, the lactate dehydrogenase (LDH) activity in the liver during exercise increased with CLA intake (about 131% compared to the non-exercise group) (FIG. 3).
Furthermore, when exercised, there is a phenomenon in which muscle cells are damaged by chemical stress due to physical and active oxygen, and enzymes necessary for muscle function deviate from the muscle cells into the blood. As a result of measuring two types of enzymes, LDH and creatine kinase (CK), which mainly deviate from the muscles into the blood due to exercise load, the CLA intake group at the time of exercise showed a low value, and blood enzyme deviation was suppressed (About 43% and 28%, respectively, for the control) (FIGS. 4 and 5). In particular, CK is an enzyme that exists specifically in muscle and can be handled as an indicator of deviating enzyme. From this, the ability to suppress the deviation of enzymes required for muscle function from muscle cells from muscle shows the effect of suppressing the decline of long-term exercise ability under exercise, increasing exercise endurance, after exercise training This has the effect of shortening the recovery time, and the improvement effect of endurance by CLA intake has been confirmed.
[Preparation Example 1] Preparation of Conjugated Linoleic Acid-Containing Fatty Acid 9sis, 11trans-conjugated linoleate by conjugating linoleic acid by an alkaline conjugation reaction (Patent No. 3017108) using safflower oil as a raw material and propylene glycol as an organic solvent A conjugated linoleic acid-containing fatty acid mixture containing equal amounts of isomers of acid and 10trans, 12cis-conjugated linoleic acid (remaining components were other isomers and other fatty acids) was obtained. This was used as CLA of Example 1.

[Examples of food and beverage]
Mayonnaise (wt%)
CLA 1.0
Oil 69.0
Egg yellow 15.0
Food Vinegar 13.0
Food salt 2.0

[Pharmaceutical formulation example]
Using CLA powder prepared by pulverizing CLA, tablets were produced in accordance with a conventional method with the following composition.
(weight%)
CLA powder 40.0
Crystalline cellulose 4.0
Sucrose ester 2.0
Shellac 2.6
Sucrose 30.0
Talc 0.1
Calcium carbonate 0.5
Lactose 18.7
Titanium oxide 0.1
Pullulan 0.04
Gelatin 1.2
Guar gum 0.2
Caramel color 0.56

The graph which shows the influence of the conjugated linoleic acid (CLA) intake on blood hemorheology. The graph which shows the influence of conjugated linoleic acid intake and running exercise load on serum lactic acid concentration. The graph which shows the influence of conjugated linoleic acid intake and running exercise load on the lactate dehydrogenase (LDH) activity of the liver. The graph which shows the influence of conjugated linoleic acid intake and running exercise load on serum LDH concentration. The graph which shows the influence of conjugated linoleic acid intake and running exercise | movement load on serum creatine kinase (CK) density | concentration.

Claims (5)

  An agent for improving athletic ability or improving blood properties based on a decrease in blood lactate concentration or suppression of intramuscular enzyme escape into the blood, comprising conjugated linoleic acid as an active ingredient. Yu away fatty conjugated linoleic acid, alcohols salt thereof, an ester, sterols, sugars, and polyglycerol or esters of ascorbic acid or an active ingredient a form selected from a mixture of two or more thereof, An agent for improving exercise ability or improving blood properties based on a decrease in blood lactate concentration or inhibition of intramuscular enzyme escape into the blood . The ester of the conjugated linoleic acid is an ester of the conjugated linoleic acid and one or more alcohols selected from the group consisting of alcohols having 1 to 10 carbon atoms, ethylene glycol, propylene glycol, and glycerin. The improving agent according to claim 2 . The improving agent according to claim 2 , wherein the metal salt of conjugated linoleic acid is one or two or more salts selected from the group consisting of sodium salts, potassium salts, calcium salts, zinc salts, and magnesium salts.     The athletic ability improvement or blood property improvement agent according to any one of claims 1 to 4, which is used as a medicine.

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