JPWO2018066394A1 - Composition for softening muscles - Google Patents

Abstract

Provided is a composition that enhances muscle flexibility by ingestion. It is a composition for softening muscles by oral intake containing an n-3 polyunsaturated fatty acid as an active ingredient. The n-3 highly unsaturated fatty acid is preferably in the form of a free fatty acid, a lower alcohol ester, or a glyceride or phospholipid containing an n-3 highly unsaturated fatty acid as a constituent fatty acid, specifically, eicosapentaenoic acid, Examples include docosapentaenoic acid or docosahexaenoic acid, refined fish oil, refined krill oil, and refined microbial oil.

Description

  The present invention relates to a composition for softening muscles. In particular, it is a composition for ingestion in order to increase the flexibility of skeletal muscle, which is said to affect motor function.

  Muscle flexibility is an important factor for health promotion and injury prevention, and it is considered that sports injury can be prevented and reduced by maintaining and improving muscle flexibility (Non-patent Document 1). In addition, muscle flexibility and sports performance are also related, and it is known that running economy is improved by improving muscle flexibility by stretching (Non-patent Document 1). Therefore, it is considered that improving muscle flexibility leads to prevention / improvement of injury and improvement of exercise performance (Non-Patent Document 1).

  Fish oil is rich in polyunsaturated fatty acids (hereinafter also referred to as PUFA) such as eicosapentaenoic acid (hereinafter also referred to as EPA) and docosahexaenoic acid (hereinafter also referred to as DHA). By doing so, it is considered that blood viscosity is reduced and the onset of cardiovascular diseases such as myocardial infarction and cerebral infarction can be prevented (Non-patent Document 2). Non-Patent Document 3 reports the possibility that EPA stimulates muscle protein synthesis.

Ohshita T, Mitsuzono R, “Influence of different stretching on range of motion and running economy in long distance runners”, Jpn. J. Phys. Fitness Sports Med. 58, p395-404, 2009. Mahinda Y. Abeywardena, Richard J. Head, “Longchain n-3 polyunsaturated fatty acids and blood vessel function”, Cardiovascular Research 52, p361-371, 2001. Kamolrat T, Gray SR, “The effect of eicosapentaenoic acid docosahexaenoic acid on protein synthesis and breakdown in murine C2C12 myotubes”, Biochem. Biophys. Res. Commun. 432 (4), p593-598, 2013.

  The present invention focuses on muscle flexibility, which is attracting attention in the field of sports and geriatrics, and supports muscle flexibility by exercising and massage, etc. It is an object of the present invention to provide a composition that enhances the viscosity.

  As one of the functional mechanisms of PUFA to the cardiovascular system, it is known that PUFA having a low viscosity is taken into the erythrocyte membrane, so that the red blood cells become flexible and the blood flow becomes smooth even in narrow blood vessels. Inspired by the action of this PUFA, we hypothesized that ingestion of PUFA would bring PUFA into skeletal muscle and improve skeletal muscle flexibility. The flexibility of the skeletal muscle of rats fed with fish oil for several weeks was measured using a muscle hardness meter and rheometer. Confirmed and completed the present invention.

The gist of the present invention is a composition for softening muscles by oral intake of the following (1) to (8).
(1) A composition for softening muscles by ingestion containing n-3 highly unsaturated fatty acid as an active ingredient.
(2) The composition according to (1), wherein the n-3 highly unsaturated fatty acid is a glyceride or phospholipid containing free fatty acid, lower alcohol ester, or n-3 highly unsaturated fatty acid as a constituent fatty acid.
(3) The composition according to (1) or (2), wherein the n-3 highly unsaturated fatty acid is eicosapentaenoic acid, docosapentaenoic acid, or docosahexaenoic acid.
(4) The composition according to (1), which contains an n-3 highly unsaturated fatty acid as purified fish oil, purified krill oil, or purified microbial oil.
(5) The composition according to any one of (1) to (4), wherein the muscle is skeletal muscle.
(6) The composition according to any one of (1) to (5) for ingesting 5 to 150 mg / kg of n-3 polyunsaturated fatty acids as a daily dose.

  By ingesting the composition of the present invention, the flexibility of muscles, particularly skeletal muscles, can be increased.

It is a figure which shows the shear strength of the anterior tibial muscle of the rat extract | collected in Example 1. FIG. It is a figure which shows the muscle hardness change rate of the rat thigh in Example 2. FIG. It is a figure which shows the correlation with the shear strength of a rectus femoris muscle in the rat extract | collected in Example 2, and perinephric fat weight.

In the present invention, PUFA is a fatty acid having 18 or more carbon atoms and 3 or more double bonds, preferably a fatty acid having 20 or more carbon atoms and 3 or more double bonds, more preferably 20 or more carbon atoms and a double bond. It is a fatty acid having 4 or more bonds. Examples of the n-3 PUFA include α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid.
The PUFA used in the present invention can be used in the form of glycerides or phospholipids containing free fatty acids, lower alcohol esters, or n-3 highly unsaturated fatty acids as constituent fatty acids. Preferably, esters with glycerin, i.e. triglycerides, diglycerides, monoglycerides, or phospholipids, i.e. Or an ester with a lower alcohol (having 1 to 3 carbon atoms), that is, a methyl ester, an ethyl ester, or the like. Preference is given to those containing n-3 fatty acids as the main component, such as EPA and DHA, and substantially free of n-6 fatty acids. Specifically, the total of n-6 fatty acids is 10% by weight or less, preferably 5% by weight or less.
Specifically, as triglycerides, refined fish oil, refined microbial oil, or concentrated oil with a higher concentration of n-3 PUFA contained in them (enzyme reaction, chemical reaction to increase the concentration of n-3 PUFA in refined fish oil) Concentrated) can be used. Moreover, refined krill oil, refined microbial oil, etc. can be used as a phospholipid. N-3 PUFA sources containing EPA and DHA include fish and shellfish extracts, animal extracts, egg yolk extracts, plant extracts, fungal extracts, etc., preferably krill oil, fish oil, squid extract, skipjack ovary extract Products, extracts of genetically modified plants, extracts of Labyrinthula, and the like. Examples of the material containing a large amount of phospholipid include krill oil and squid extract. The phospholipid concentration and purity in these materials can be arbitrarily adjusted by using techniques generally known in the art such as concentration, extraction, and / or purification, and blending.

  EPA and / or DHA are known to be effective for hyperlipidemia and allergic symptoms, and many pharmaceuticals and various supplements are already on the market. For the purposes of the present invention, capsule preparations similar to these can be used. Specifically, a product obtained by processing a fat and oil obtained by adding an antioxidant to purified fish oil into a gelatin capsule is often used. The dosage form of the preparation is not particularly limited as long as it is an orally administrable dosage form, and is a tablet, capsule (hard capsule, soft capsule), microcapsule, granule, fine granule, powder, oral liquid preparation (emulsion, Suspensions, etc.), syrups, jellies and the like. For example, a dosage form enclosed in a capsule, particularly a soft capsule or a microcapsule is preferable. Each formulation is prepared by methods known in the art, and usually used excipients, diluents, binders, wetting agents, disintegrants, disintegration inhibitors, absorption enhancers, lubricants, solubilizers, Prepared using buffers, emulsifiers, suspending agents and the like. Additives include stabilizers, preservatives, buffers, isotonic agents, chelating agents, pH adjusters, surfactants, colorants, flavoring agents, flavoring agents, sweetening agents that are usually used depending on the dosage form. An agent or the like can be used. The amount of n-3 PUFA contained in the preparation is, for example, 20% by weight or more, preferably 40% by weight or more, or 50% by weight or more, more preferably 80% by weight or more as the total amount of n-3 PUFA. is there.

As the refined fish oil, any fish oil may be used as long as it contains EPA and DHA. Examples of fish oils rich in EPA include sardine oil and cod liver oil, and examples of fish oils rich in DHA include tuna oil and bonito oil.
The concentrated oil of PUFA is a fat and oil in which the concentration of EPA / DHA in the triglyceride of refined fish oil is increased by using a lipase having regioselectivity and fatty acid selectivity.

In the composition of the present invention, n-3 PUFAs such as EPA and DHA are preferably taken orally in a total amount of 5 to 150 mg / kg per day. More preferably, it is 15-150 mg / kg, Most preferably, it is 15-75 mg / kg. It may be taken at once or divided. It is preferable to ingest continuously, and the effect is recognized by continuous administration for at least 2 weeks.
n-3 PUFA is a food-derived ingredient, and since it has already been used for a long time in other applications, it can be safely consumed.

In the composition of the present invention, since the active ingredient is extremely safe, the use target is not particularly limited, and it can be used for subjects who want to soften muscles, from young people to elderly people. It is particularly preferable for those who perform sports or those who are concerned about muscle hardening due to age. It can also be applied to mammalian animals as objects of use. It is particularly preferable to use it for competition animals such as horses and dogs.
The composition of the present invention can be ingested as a food or together with a food ingredient because the active ingredient is extremely safe.
Examples of the present invention will be described below, but the present invention is not limited thereto.

<Experiment method>
1. Experimental animals 7-week-old Wistar male rats were used as animals. The experiment was conducted after one week of pre-breeding. Rats were divided into 2 groups (6 groups), EPA / DHA-rich fish oil-added feed intake group (fish oil group) and lard-added feed intake group (Lard group). The feed was pair-feeded and the food intake was adjusted. Water was ad libitum. The animals were housed in individual cages made of stainless steel in a conditioned animal room with a room temperature of 22 ± 2 ° C., 50 ± 10% humidity, and illumination for 12 hours.
2. Feed and feeding period AIN-93G modified feed solidified in pellet form containing 15% each of fish oil (manufactured by Nippon Chemical Feed Co., Ltd.) and lard (manufactured by Oriental Yeast Co., Ltd.) Obtained from. Table 1 shows the fatty acid composition of the fish oil and lard used, and Table 2 shows the composition of the AIN-93G modified feed. The feeding period was 4 weeks. After the breeding period, the anterior tibial muscle (TA) was collected and stored frozen at −80 ° C. until analysis.

3. Shear titration measurement The weight of the anterior tibial muscle was measured while cooling the sample stored at −80 ° C. with liquid nitrogen. After the weight measurement, the sample was thawed for 24 hours in a low-temperature room in a tube. The moisture exuded from the thawed muscle tissue was wiped with a paper towel and weighed, and the shear strength was measured with a rheometer (RE-3305S, manufactured by YAMADEN, shear rate 1 mm / sec).

<Result>
The total intake of feed for 4 weeks was 708.9 ± 31.4 g in the fish oil group and 695.1 ± 27.6 g in the lard group. The daily intake of EPA and DHA in the fish oil group was about 765.8 mg and about 307.8 mg, respectively. The weights of the anterior tibial muscles in the fish oil group and lard group were 1.42 ± 0.05 g and 1.42 ± 0.02 g, respectively.
When the shear strength of the fish oil group and lard group was measured, a tendency was observed that the shear strength of the fish oil group was smaller than the shear strength of the lard group (FIG. 1). Fish oil intake has been shown to increase skeletal muscle flexibility.

<Experiment method>
1. Experimental animals Four-week-old Wistar male rats were used as animals. The experiment was conducted after one week of pre-breeding. Rats were divided into fish oil group or lard group (6 animals per group) and allowed to eat freely for 4 weeks. Water was ad libitum. The animals were housed in individual plastic plastic cages in an air-conditioned animal room with a room temperature of 22 ± 2 ° C, 50 ± 10% humidity, and illumination for 12 hours.
2. Feed and feeding period
7% soybean oil contained in AIN-93G is fish oil (fish oil with high content of EPA / DHA made by Nihon Suisan Co., Ltd., containing 40% or more of EPA / DHA in total fatty acids) or lard (made by Oriental Yeast Co., Ltd.) ) AIN-93G modified feed was prepared. A powder feed obtained by removing soybean oil from AIN-93G was obtained from Oriental Yeast Co., Ltd. Table 3 shows the fatty acid composition of the fish oil used, and Table 4 shows the component composition of the feed used. The same lard as in Table 1 was used. The feeding period was 4 weeks. After the breeding period, the animals were dissected and the weight of each organ was measured and the shear strength of skeletal muscle was measured. In addition, during pre-breeding, thigh muscle hardness was measured at 2 weeks after the start of test feed intake and 4 weeks after the start of intake.

3. Measurement of muscle hardness Rats were held and the muscle hardness of the thigh of the right hind paw was measured using a muscle hardness meter (NEUTONE TDN-N1, manufactured by TRY-ALL). The measurement was carried out 3 times in succession for each animal, and the average value of 3 times was taken as the measured value. Based on the value of muscle hardness during pre-breeding, it was set to 100%, and the subsequent change in muscle hardness was expressed as the rate of change.
4. Shear strength measurement At the time of dissection, the anterior tibialis and rectus femoris were collected, the muscles were cut with a cutter with both ends fixed with two pins, and the shear strength at that time was measured with a rheometer (RE -3305S, manufactured by YAMADEN, shear rate 1 mm / sec).

<Result>
The total intake for 4 weeks per animal was about 544 g in the fish oil group and about 585 g in the lard group. The daily intake of EPA and DHA in the fish oil group was about 345.0 mg and about 153.5 mg, respectively.

The results of the muscle hardness change rate are shown in FIG. In the fish oil group, the muscle hardness of the thigh became softer over time at 2 and 4 weeks after the start of test feed intake. On the other hand, in the lard group, there was no change from before intake at 2 weeks after ingestion, and it became softer by about 10% at 4 weeks after ingestion. When compared between the two groups, the muscle hardness of the fish oil group was significantly lower at 2 weeks after the start of intake. From these results, it was shown that the fish oil diet improves muscle flexibility compared to the lard diet.
Table 5 shows the shear titers of the anterior tibial muscle and rectus femoris at 4 weeks after the intake of the test feed. In the tibialis anterior and rectus femoris, the fish oil group showed lower shear strength than the lard group. These results also showed that the fish oil diet improved muscle flexibility compared to the lard diet.

  FIG. 3 shows the correlation between the rectus femoris shear strength and the weight of perirenal fat at 4 weeks after the start of test feed intake. There was no correlation between the two in the lard group, but there was a significant positive correlation in the fish oil group. These results indicate that the rectus femoris muscle became softer as the weight of the perirenal fat decreased with fish oil intake, suggesting that the individual with higher sensitivity to fish oil increases muscle flexibility. This result also supported the increased muscle flexibility in the fish oil diet compared to the lard diet. Based on the above results, it was considered that the intake of PUFA increases the flexibility of skeletal muscle.

In the field of sports and geriatric medicine, skeletal muscle stiffness is considered unfavorable and has been made flexible by training and massage. Since the composition of the present invention has the effect of softening muscles by oral administration, it can be used in the sports field and geriatric field by taking it as a pharmaceutical or a supplement.

Claims (6)

  A composition for softening muscles by ingestion containing an n-3 polyunsaturated fatty acid as an active ingredient.   The composition of claim 1, wherein the n-3 highly unsaturated fatty acid is a free fatty acid, a lower alcohol ester, or a glyceride or phospholipid containing the n-3 highly unsaturated fatty acid as a constituent fatty acid.   The composition according to claim 1 or 2, wherein the n-3 polyunsaturated fatty acid is eicosapentaenoic acid, docosapentaenoic acid, or docosahexaenoic acid.   The composition of Claim 1 which contains n-3 type | system | group highly unsaturated fatty acid as refined fish oil, refined krill oil, and refined microbial oil.   The composition according to any one of claims 1 to 4, wherein the muscle is skeletal muscle. The composition according to any one of claims 1 to 5 for ingesting 5 to 150 mg / kg of n-3 polyunsaturated fatty acids as a daily dose.

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