HK1126663B - Composition containing riboflavin and sesamins - Google Patents

Description

Composition containing riboflavin and sesamin compounds

Technical Field

The present invention relates to a composition capable of enhancing the physiological activity of riboflavin and containing riboflavin and sesamin compounds, and more particularly, to a composition having an analgesic effect capable of preventing and/or alleviating pain caused by various diseases and trauma, or a composition having an anti-fatigue effect capable of preventing and/or alleviating physical and/or mental fatigue, and a food or drink containing the same.

Background

Riboflavin (Riboflavin) also known as vitamin B₂(Vitamin B₂) Among vitamins, physiologically active substances are classified as water-soluble vitamins. The riboflavin is useful for preventing and treating eye diseases including cataract, and can also be used for relieving symptoms of congestion, dryness, pruritus and asthenopia (Wikipedia of encyclopedia of Ophiopedia of Ophiopediaceae: Internet)http://ja.wikipedia.org/). Further, it has been reported that riboflavin compounds have an immune function activating action as a physiological activity of riboflavin (patent document 1), and that riboflavin compounds are effective as a prophylactic and therapeutic agent for toxic shock (patent document 2).

Further, there are reports that the physiological activity of riboflavin is an analgesic effect. For example, it has an effect of preventing migraine by taking a large amount of riboflavin (non-patent document 1), and has an analgesic effect that is dose-dependent when intraperitoneal administration is performed at a concentration of 3 to 100mg/kg for inflammatory pain, but is ineffective against neuropathic pain (non-patent document 2), and has an analgesic effect of 25mg in formalin test when oral administration is performed at a concentration of 1 to 50mg/kg, and the effect does not increase even when the concentration is increased to 75mg (non-patent documents 2 and 3).

In addition, it is known to include vitamin B₂The anti-fatigue action of the vitamin B group, i.e., the fatigue recovery and fatigue prevention action of the vitamin B group (patent document 3). And contains vitamin B for intake during fatigue and skin dryness₁Vitamin B₂And vitamin B₆The nutritional supplement food and health beverage are also commercially available.

Patent document 1, Japanese patent application laid-open No. 5-201864

Patent document 2 Japanese patent application laid-open No. 10-29941

Japanese patent laid-open No. 2005-23008 of patent document 3

Nonpatent document 1Schoenen, J., NEUROLOGY, 50, 466-470, 1998

Non-patent document 2European Journal of Pharmacology, 421, 157-164, 2001

Non-patent document 3European Journal of Pharmacology, 492, 35-40, 2004

Disclosure of Invention

As described above, various reports have been made on the physiological activity of riboflavin, but the effect is still insufficient, and blending of riboflavin mainly for the purpose of supplementing the physiological activity of other compounds has not been suggested or disclosed so far as to enhance the physiological activity of riboflavin itself. Further, as described above, although the anti-fatigue action of vitamin B group is known, riboflavin (vitamin B) is known₂) The specific anti-fatigue effect of (A) has not been disclosed at all.

The purpose of the present invention is to provide a composition, particularly a food or beverage, which is safe for humans, animals and the like and can be ingested continuously and can enhance the physiological activity of riboflavin.

The present inventors have intensively studied to solve the above problems and as a result, have surprisingly found that the physiological activity of riboflavin can be enhanced by simultaneously ingesting riboflavin and sesamins. Specifically, as described above, it was found that the analgesic effect of riboflavin alone is limited when it is orally administered, but the effect of riboflavin is enhanced by taking it together with sesamin, and the analgesic effect that cannot be obtained by taking riboflavin alone can be exerted. The present inventors have also found that riboflavin has an anti-fatigue effect as a result of evaluation using a swimming test performed on a water-soaked load model animal as a model for evaluating fatigue. Further, the present inventors have found that the combined use of sesamins can exert an anti-fatigue effect which cannot be exerted by the intake of riboflavin alone and also exert an excellent synergistic effect between riboflavin and sesamins, thereby completing the present invention.

Namely, the present invention relates to a composition comprising a food or beverage as described below.

1. A composition comprising riboflavin and sesamins.

2. The composition as set forth in1 above, wherein the ratio (weight ratio) of the total amount of sesamins is 4.5 or less when the total amount of riboflavin is 1.

3. The composition according to 1 or 2, wherein the sesamin component is a sesamin component concentrate containing 1% by weight or more of sesamin component.

4. The composition according to any one of the above 1 to 3, wherein the sesamin-like substance is sesamin and/or episesamin.

5. The composition as set forth in any one of the above 1 to 4, wherein the riboflavin is any one of riboflavin sodium phosphate or riboflavin tetrabutyl ester.

6. The composition according to any one of the above 1 to 5, which is a composition for oral administration.

7. An analgesic agent which comprises riboflavin and sesamin as active ingredients.

8. An anti-fatigue agent which contains riboflavin as an active ingredient.

9. An anti-fatigue agent which contains riboflavin and sesamin as active ingredients.

10. Use of sesamin compounds for improving the physiological activity of riboflavin.

Drawings

FIG. 1 shows the effect of sesamins on analgesic action.

FIG. 2 shows a composition of riboflavin (vitamin B)₂) And sesamin compounds have analgesic effect.

FIG. 3 shows a composition of riboflavin (vitamin B)₂) And sesaminSynergistic effect of analgesic effect of the above-mentioned combination.

FIG. 4 shows the anti-fatigue effect of a combination of riboflavin and sesamins.

FIG. 5 shows the anti-fatigue effect of a combination of riboflavin and sesamins.

Detailed Description

(Riboflavin)

Riboflavins of the invention (also denoted 'vitamin B' in the present description)₂') includes riboflavin derivatives, or pharmacologically acceptable salts of such derivatives. The riboflavin derivative or a pharmacologically acceptable salt thereof may specifically be Flavin Mononucleotide (FMN), Flavin Adenine Dinucleotide (FAD), riboflavin tetrabutyrate, and riboflavin sodium phosphate (vitamin B)₂Phosphate ester), monodiiothiolamine salt of riboflavin phosphate, riboflavin tetrabutyrate (vitamin B)₂Tetrabutyl ester) norflavin (Leucoflavin), monohydroflavin, norflavin phosphate (Leucoflavin phosphate ester), norflavin mononucleotide (Leucoflavin mononucleotide), norflavin adenine dinucleotide (Leucoflavin adenine dinucleotide), and the like, but among them, sodium riboflavin phosphate having high absorbability and riboflavin tetrabutyrate having excellent stability are preferably used. In the present invention, any of the above-mentioned riboflavin may be used alone or in combination of two or more. The method for producing the above-mentioned substances is not limited at all, and any of natural extracts, microbial fermentation products, and synthetic products can be used.

(sesamin compounds)

Sesamins of the present invention include sesamin and analogues thereof. Examples of the sesamin analogs include, in addition to episesamin, dioxabicyclo [3.3.0] octane derivatives described in Japanese patent application laid-open No. 4-9331. Specific examples of sesamins include sesamin, sesamol (sesaminol), episesaminol (episesaminol), sesamolin (sesamolin), and the like, and stereoisomers and racemates of these substances may be used alone or in combination. Metabolites of sesamins (for example, as described in japanese patent application laid-open No. 2001-139579) are sesamin analogs contained in sesamins of the present invention, and can be used in the present invention as long as the effects of the present invention are exhibited.

The sesamin-based compound used in the present invention is not limited in any way, such as its form and production method. For example, when sesamin is selected from sesamins, sesamin (as a sesamin extract or a purified product) extracted from sesame oil by a known method (for example, the method described in jp-a-4-9331) can be usually used, but commercially available sesame oil (liquid) may be used as it is. However, when sesame oil is used, since sensory evaluation of the flavor peculiar to sesame oil is not desirable in some cases, it is preferable to use a sesamin extract (or a sesamin purified product) which is extracted from sesame oil and is odorless. In addition, when sesame oil is used, since sesamin content is low, riboflavin (vitamin B) is required to be contained when an appropriate amount of sesamin is blended₂) The composition of (a) is too large in volume per administration unit, and causes inconvenience in ingestion. In particular, when a preparation is formed for oral administration, the preparation (tablet, capsule, etc.) is too large, and intake is hindered. Therefore, it is preferable to use a sesamin extract (or a sesamin purified product) in sesame oil from the viewpoint that the smaller the intake amount, the better.

Thus, a concentrate of sesamin is preferably used as the sesamin. The concentration degree may be appropriately set according to the kind of the sesamin component and the form of the composition to be blended, but it is generally preferable to use a sesamin component concentrate in which the concentration is not less than 1% by weight of the sesamin component. The content of sesamin component in the sesamin component concentrate is preferably 20% by weight or more, more preferably 50% by weight or more, further preferably 70% by weight or more, and most preferably a concentrate concentrated (purified) to 90% by weight or more.

As described above, it is obvious that sesamins used in the present invention are compounds found in conventional foods or similar compounds thereof and therefore are excellent in safety. This was also confirmed from the following experiment that no abnormal symptoms were observed when sesamin was administered (orally) to 7-week-old ICR male mice at 2.14g/day/kg for 2 weeks.

Although sesamins, particularly sesamin and/or episesamin, used in the present invention have been found to have an autonomic nerve-regulating effect (international publication WO 2004-105749), the present applicant has not known any effect of enhancing the analgesic effect and the anti-fatigue effect of the present invention, and has never disclosed or suggested a conclusion that the physiological activity of riboflavin is enhanced.

(analgesic and drug)

The present invention is very effective as an analgesic for preventing and/or reducing pain in humans or animals, particularly humans. Herein, the animal means farm animals, pet animals and laboratory animals, specifically, farm animals means livestock such as cattle, horses, pigs, goats and sheep, poultry such as chicken, duck, quail, turkey and ostrich, and fish such as yellowtail, gargarish, horse mackerel, carp, rainbow trout and eel; the pet animal is a so-called pet animal such as dog, cat, marmoset, bird, hamster, and goldfish, and is also called a companion animal; the experimental animal refers to an animal used for research in the fields of medicine, biology, agriculture, pharmacy, and the like, such as a mouse, a rat, a guinea pig, a Beagle (Beagle), a mini pig, a macaque, and a cynomolgus monkey.

The analgesic of the present invention is intended for mild pain of the transient type to intolerable pain of the chronic type. Pain can be controlled by using an analgesic agent, but the effect is not necessarily sufficient, and chronic pain (pain) such as arthralgia, neuralgia, lumbago, etc. can be suppressed only temporarily, or side effects such as gastrointestinal disorders, renal disorders, liver disorders, etc. are caused by continuous administration of an analgesic agent. Further, the pain such as arthralgia, neuralgia and lumbago tends to increase with the aging, and with the rapid aging in recent years, there is no longer a demand for simple improvement and removal of pain, and social demand for prevention of pain is increasing.

The analgesic agent of the present invention is very effective against the above-mentioned various pains and diseases associated with these pains. The analgesic agent of the present invention can synergistically enhance the analgesic activity of riboflavin by using sesamins in combination, and can exhibit an excellent analgesic activity as compared with conventional analgesic agents. Moreover, riboflavin and sesamin compounds which are ingested as foods and drinks for a long time are used as active ingredients, and therefore, the composition has no side effects and can be ingested continuously. Therefore, daily intake of the compound is expected to reduce chronic pain and prevent diseases (menstrual pain, etc.) associated with pain, and thus the compound is a novel analgesic. In view of the above, the present invention is also very effective in that a person who feels strong and a person who does not feel strong have a difference in their feelings of pain, and there is no objective scale, and there are many cases where a normal condition or a pathological condition cannot be clearly determined.

(anti-fatigue action and agent)

The composition of the present invention is effective as an anti-fatigue agent for human and animals, in addition to the analgesic effect described above. Here, the animal refers to an animal to be treated with the analgesic, but among them, the anti-fatigue agent of the present invention is applicable to a human, a farm animal, a pet animal, and a laboratory animal, which can sense fatigue, and is particularly preferably applicable to a human. Farm animals include livestock such as cattle, horses, pigs, goats, and sheep, racehorses, beagles, and the like, pet animals include dogs and cats, and laboratory animals include mice, rats, guinea pigs, beagle dogs, mini pigs, macaques, and cynomolgus monkeys, and the like, which are used for research in the fields of medicine, biology, agriculture, and pharmacy.

Fatigue refers to a phenomenon in which physical and mental performance decreases temporarily when a physical or mental load is continuously applied, and the decrease in performance refers to a decrease in quality or quantity of physical and mental work ability. The fatigue of the invention comprises chronic fatigue syndrome and overwork death.

The anti-fatigue agent of the present invention means an action of reducing the above-mentioned fatigue and an action of recovering the fatigue, and specifically means an effect of improving the duration of work of a sport or work site (including a brain), suppressing an increase in fatigue substances (improving endurance and enhancing physical strength) under the same amount of exercise or work, improving a state in which the brain, nerves, etc. feel fatigue even though the sport or work site is not fatigued, and promoting recovery of the fatigue state of the sport or work site to a normal state.

The objective chronic fatigue syndrome to which the anti-fatigue agent of the present invention is directed is a long-term, basic symptom such as general fatigue, burnout, low fever, swollen lymph nodes, muscle pain, joint pain, mental nerve symptom, etc., which causes a disorder in daily life. The anti-fatigue agent of the present invention can treat the chronic fatigue syndrome, i.e., alleviate various symptoms of the chronic fatigue syndrome to shift to a normal state. The purpose of the anti-fatigue agent of the present invention is to prevent fatigue from being perceived sufficiently even though physical activity is not maintained in a severe state of strain, and as a result, cerebrovascular diseases and cardiac diseases are caused to occur, resulting in permanent disability or death. The anti-fatigue agent of the present invention can treat chronic fatigue syndrome and prevent death due to fatigue.

The anti-fatigue effect of the present invention, i.e., the effect of the "anti-fatigue agent", can be confirmed, for example, by the measurement of swimming time in the soaked sleep deprivation test. Mice raised in an environment in which sufficient sleeping and resting postures cannot be obtained under the water-immersed raising condition and no physical or mental rest can be obtained were made to swim under a load, and the fatigue was confirmed by measuring the time until the nose of the mice swims until the mice were submerged in water for 10 seconds or more. Since this animal model is a physical and mental fatigue model, if the swimming time can be prolonged by administering a test substance, it is confirmed that the animal model can prevent or improve physical and mental fatigue and muscular pain and the like caused by physical and mental fatigue, can increase physical strength to extend the time to exhaustion, can maintain physical activity in a fatigue state, and the like, and can be resistant to fatigue.

The anti-fatigue agent of the present invention is less likely to feel fatigue by taking the anti-fatigue agent, and has an effect of recovering from fatigue. That is, when the patient feels physical fatigue during muscle exercise such as physical exercise or when the patient feels mental fatigue during continuous work such as calculation, recovery from fatigue can be expected, and it is needless to say that fatigue can be prevented even when the patient takes the drug in advance and then performs work or physical exercise. And by taking before or during the performance of physical exercise, it is expected to improve endurance. And can be taken daily for preventing mental fatigue and diseases caused by mental fatigue.

(composition containing riboflavin and sesamin component)

The present invention is intended to enhance the physiological activities of riboflavin, such as analgesic activity and anti-fatigue activity, by incorporating sesamin in riboflavin, and to achieve the purpose of promoting health by utilizing the riboflavin as a health food and by utilizing the physiological activities of the respective ingredients.

The amount of riboflavin and sesamin in the composition of the present invention is not limited as long as physiological effects of each can be expected. In general, riboflavin is compounded in the amount required for the nutrition of Japanese as prescribed in Ministry of labour and welfare, specifically, 1.2mg for adult male and 1.0mg for adult female every 1 day. Further, there is no report on the maximum limit of health disorders caused by riboflavin, and therefore there is no upper limit to the amount of riboflavin to be added, but it is usually 100mg or less, preferably 50mg or less per 1 day for an adult. The amount of sesamin to be blended is usually about 1 to 200mg, preferably about 5 to 100mg per 1 day for an adult.

On the other hand, it is expected that the physiological activity of riboflavin is enhanced, and when sesamins are blended into riboflavin, the total amount ratio of sesamins blended is 4.5 or less, preferably 4.0 or less, and more preferably 3.5 or less by weight based on the total amount of riboflavin 1 (in this specification, also referred to as "riboflavin equivalent"). Although it is expected that the higher the proportion of sesamins to be blended, the more the effect of riboflavin is enhanced, if the proportion is not within the above range, a good synergistic effect cannot be obtained. The lower limit of the sesamin component to be blended is not limited as long as the synergistic effect of the desired effect, for example, analgesic effect and anti-fatigue effect can be obtained, and the amount can be blended with reference to the above daily dose. In general, the total amount of sesamins is 0.01 or more, preferably 0.5 or more, more preferably 0.1 or more, and further preferably 1 or more in terms of riboflavin, based on the total amount of riboflavin 1.

In the analgesic action of riboflavin, which is one of the physiological activities, it has been confirmed that when riboflavin sodium phosphate having a riboflavin equivalent of 30mg and sesamins having a riboflavin equivalent of 50mg or 100mg are orally ingested, the weight ratio of riboflavin: sesamin 1: 1.67 or 1: 3.33, the analgesic effect of riboflavin sodium phosphate was improved (examples 1 and 2). In the anti-fatigue effect, which is one of the physiological activities of riboflavin confirmed by the present inventors, when riboflavin sodium phosphate having a riboflavin equivalent of 25mg or 50mg and 50mg of sesamin are orally ingested, the weight ratio of riboflavin: sesamins group 1: 2 or 1: 1, the anti-fatigue effect of riboflavin sodium phosphate can be improved, but when the riboflavin sodium phosphate with 10mg of riboflavin equivalent and 50mg of sesamin are taken orally, the weight ratio of riboflavin: sesamins group 1: 5, but did not enhance the anti-fatigue effect of riboflavin sodium phosphate (examples 3, 4).

When the composition of the present invention is used as a pharmaceutical composition, the administration form thereof may be oral administration in the form of a liquid, tablet, granule, powder, capsule, dry syrup, pill, or the like, or administration in the form of an injection or the like, and the form thereof may be appropriately selected depending on the condition of a disease, the state of progression thereof, and other conditions. In addition, riboflavin (other than riboflavin tetrabutyl ester) as an active ingredient of the present invention is water-soluble, and sesamin-based compounds are fat-soluble, and therefore, they may be taken in other forms. Specifically, the analgesic effect can be achieved by a method of taking a soft capsule in which the riboflavin particles are taken together with water and sesamin is dissolved in oil and fat and then filled, or a method of taking the riboflavin particles with a time difference set depending on the absorption rate.

The dose of the composition of the present invention may be appropriately selected depending on the subject, the disease condition, the progress thereof, other administration forms, etc., but when the composition is orally administered for the purpose of obtaining analgesic effect and/or anti-fatigue effect in the case of human (adult), it is usually administered continuously at a frequency of about 1 to 3 times per 1 day, about 1 to 200mg, preferably about 2 to 100 mg.

In the present invention, any desired component other than riboflavin and sesamins may be added as long as the effect is not impaired. For example, in addition to physiologically active ingredients such as vitamins such as vitamin E and vitamin C, minerals, hormones, nutritional ingredients, and perfumes, emulsifiers, tonicity agents (isotonic agents), buffers, solubilizing agents, preservatives, stabilizers, and antioxidants which can be incorporated when forming a preparation can be appropriately incorporated. The composition of the present invention can be used as an analgesic and/or an anti-fatigue agent as described above, but it is considered that riboflavin (vitamin B) can be additionally or synergistically expressed₂) And sesamin-like substances, and therefore, it is preferably used not only in the above-mentioned pharmaceutical compositions but also in health foods.

The health food as referred to herein includes preparations or foods containing the composition itself containing riboflavin and sesamin compounds of the present invention as an active ingredient, such as capsules and tablets, and functional foods (including specific health foods and health foods with specific conditions) in general foods in which various functions such as analgesic action and anti-fatigue action on the living body are imparted by blending the composition of the present invention as one of the ingredients. And further includes foods and the like, which are characterized by having a marker for the purpose of preventing or relieving pain in the living body, for the purpose of relieving fatigue in the living body or promoting recovery from fatigue, and having an analgesic effect and/or an anti-fatigue effect.

Health food containing riboflavin and sesamin is in a form of, for example, solid such as powder, granule, or tablet, without any particular limitation; a liquid such as a solution, an emulsion, or a dispersion; or a semisolid state such as a paste.

Examples

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

Test example 1 analgesic Effect of sesamin Compounds

There is no report on analgesic activity of sesamins. Therefore, the analgesic effect of sesamin compounds has been studied.

The analgesic effect test was carried out by a method in which a part of the Writhing test (biol. pharm. Bull. (2005)) by Moon et al was changed. The specific test method is as follows. Male rats of the Wistar line (5 weeks old) were purchased from japanese clean corporation (clean Japan, Inc.), acclimatized in a test environment for 1 week, and then animals showing smooth development were used for the test. Before 3 days of the acetic Writhing (writting) test, the rats were divided into 3 groups of 6 rats each, the control group was administered olive oil orally at a dose of 5ml/kg using a probe, and the remaining 2 groups were administered sesamins [ sesamin/episesamin mixture; sesamin: episesamin (weight ratio) 5: 5] dissolving in oleum Olivarum at a dosage of 50mg/kg and 100mg/kg, respectively, and orally administering with probe. Then, the same administration was carried out 2 days before the test, and 2 administrations were carried out in the morning and evening of the day before the test, that is, 4 administrations were carried out in total. On the test day, the rats deprived of food overnight from the previous day of night were orally administered with physiological saline at 5ml/kg, and 1 hour later, the rats were intraperitoneally administered with physiological saline containing 1% acetic acid at 1ml/170g, and the number of writings (writings) was counted from the beginning of administration within 30 minutes.

The results are shown in FIG. 1. The Sesamin-containing group (Sesamin50mg, Sesamin100mg) showed a tendency of increasing the number of writings (writings) compared with the control group (Olive), and demonstrated that Sesamin-containing group had no analgesic effect in the writings with acetic acid (writings) test.

Example 1 Riboflavin (vitamin B) ₂ ) Analgesic action with sesamin component (1)

It was confirmed that sesamin compounds increase riboflavin (vitamin B)₂) Has analgesic effect. Wi star male rats (7 weeks old) were purchased from Japanese clean corporation (clean Japan, Inc.), and animals that showed smooth development were used for the test after acclimatization in a test environment for 1 week. 6 rats were divided into 4 groups 3 days before the Writhing with acetic acid (writting) test, of which 2 groups were orally administered with 5ml/kg of olive oil using a probe, and the remaining 2 groups were orally administered with 50mg/kg and 100mg/kg of sesamins dissolved in olive oil (5ml/kg) using a probe, in the same manner as in test example 1, and a total of 4 administrations were performed in the same manner as in test example 1. On the test day, rats deprived of food overnight from the night of the previous day, the control group was orally administered with 5ml/kg of physiological saline, and vitamin B was administered to the remaining 3 groups₂(sodium Riboflavin phosphate; nacalai tesque Co.) an amount of 30mg/kg of riboflavin equivalent was dissolved in physiological saline and orally administered, and the number of writings (writings) was calculated according to test example 1.

The results are shown in FIG. 2. Number of Writhing (writting) in vitamin B relative to control group (Olive + Saline)₂The individual group (Olive + VB2) showed a trend towards reduction, demonstrating vitamin B₂Has analgesic effect. With vitamin B₂Sesamins and vitamin B compared with the individual group (Olive + VB2)₂The combination group (Sesamin50mg + VE2, Swsamin100mg + VE2) exhibited a reduction in the number of writings (writings) in either of the sesamins group at 100mg/kg and 50 mg/kg. Demonstration of vitamin B by combination with sesamins₂The analgesic effect of the composition is enhanced.

Example 2 Riboflavin (vitamin B) ₂ ) Analgesic action with sesamin component (2)

The reproducibility of example 1 was confirmed. Male rats of the Wistar line (5 weeks old) were purchased from japanese clean corporation (clean Japan, Inc.), acclimatized in a test environment for 1 week, and animals showing smooth development were used for the test. 10 to 18 groups of rats were divided into 4 groups 3 days before the acetic Writhing (writting) test, of which 2 groups (1 group and 2 groups) were orally administered with olive oil at 5ml/kg using a probe, and the remaining 2 groups (3 groups and 4 groups) were orally administered with a probe, in which sesamin was dissolved in olive oil at 100mg/kg in the same manner as in example 1, and were orally administered with a probe, and the total of 4 administrations were performed in the same manner as in example 1. On the day of the experiment, physiological saline was orally administered at 5ml/kg to 2 groups (1 group, 3 groups) of 4 groups of rats deprived of food for one night from the previous day night, and vitamin B was administered to the remaining 2 groups (2 group, 4 group)₂(sodium riboflavin phosphate; nacalai tesque Co.) was orally administered in an amount of 30mg/kg of riboflavin equivalent dissolved in physiological saline, and the number of writings (writings) was calculated according to the method of test example 1.

The results are shown in FIG. 3. Vitamin B relative to Writhing (writting) number of control group (Olive + Saline)₂The decrease tendency (inhibition rate 10.5%) was observed in the group alone (Olive + VB2), and the analgesic effect was not observed in the group alone with Sesamin (Sesamin + Saline) as in test example 1, but vitamin B was observed in the group alone₂The combination with Sesamin (Sesamin + VB2) showed a dramatic decrease (inhibition 26.6%), demonstrating vitamin B₂Synergistic analgesic effect with sesamin (results of Tukey's multiple comparison test, between combination of vitamin B2 and sesamin and control, p)<0.05, with sesamin group alone, p<0.01)。

Example 3 anti-fatigue Effect of Riboflavin and sesamins (1)

The tested substances, riboflavin and sesamins, were the same as in example 1, except that a sesamin/episesamin mixture (sesamin: episesamin (weight ratio): 5) and riboflavin (sodium riboflavin phosphate; nacalai tesque corporation) were used.

The effect on fatigue was evaluated by a soaked sleep deprivation test. The evaluation was carried out by modifying a part of the method of Tanaka et al (neuroscience, let.352, 159-162, 2003). That is, 1 group of 9 animals was tested using 8-week-old male Balb/c mice, and the mice were divided into 7 groups as shown in Table 1, so that the average body weight of the mice was equalized. The riboflavin values in Table 1 indicate the values in terms of riboflavin sodium phosphate to be used. Of these, 6 groups were used as a sleep deprivation stress group in place of a floor mat (sheet), and were raised by placing tap water having a water temperature of 23 ℃ in a raising tank so that the water depth was 7mm, thereby subjecting the mice to sleep deprivation in the water. In the case of 2-day soaking sleep deprivation, each of the samples to be tested was administered sesamin1 time a day and orally for 2 days. In the test sample, sesamin was dissolved in olive oil, and riboflavin was dissolved in distilled water. The administration sequence was such that riboflavin and sesamin were administered orally in the order of the administration, and the oral administration was forced with distilled water and olive oil.

After 2 days of immersion, the mice were added with a weight corresponding to 8% of their body weight at their tails and then swim, and the time until they swim to submerge in water was measured for 10 seconds or more. The mice in the water-soaked breeding group (water-soaked sleep deprivation-stressed group) had shorter swimming times than the mice in the normal breeding group, but the effect on fatigue was determined by how much the mice in the test sample administration group could suppress the shortening of swimming time.

TABLE 1

Group 1(cont) control group distilled water + olive oil was generally maintained

Group 2 immersion breeding control group distilled water + olive oil

Group 3 Riboflavin group Riboflavin 25.0mg/kg + Olive oil by soaking in water

Group 4 Riboflavin group Riboflavin 50.0mg/kg + Olive oil by soaking in water

Group 5 Water-soaked Sesamin group of distilled water and Sesamin 50.0mg/kg

Group 6 was water-soaked to feed riboflavin + sesamin group riboflavin 25.0mg/kg + sesamin 50.0mg/kg

Group 7 was water-soaked to feed riboflavin + sesamin group riboflavin 50.0mg/kg + sesamin 50.0mg/kg

The results are shown in FIG. 4. As can be seen from the figure, the swimming time of the control group fed in water was shortened as compared with the control group fed in general. On the other hand, administration groups of sesamin and riboflavin suppress the shortening of swimming time, respectively, and the effect thereof can be synergistically enhanced by administering them simultaneously.

Example 4 anti-fatigue Effect of Riboflavin and sesamins (2)

Except that the mice were divided into 6 groups as shown in table 2, the anti-fatigue effects of riboflavin and sesamins were measured in the same manner as in example 3. The riboflavin values in Table 2 indicate the values in terms of riboflavin sodium phosphate to be used.

TABLE 2

Group 1(cont) control group distilled water + olive oil was generally maintained

Group 2 immersion breeding control group distilled water + olive oil

Group 3 Riboflavin group Riboflavin 10.0mg/kg + Olive oil by soaking in water

Group 4 Water-soaked Sesamin group of distilled water and Sesamin 50.0mg/kg

Group 5 was water-soaked to feed riboflavin + sesamin group riboflavin line 10.0mg/kg + sesamol 50.0mg/kg

Group 6 was water-soaked to feed riboflavin + sesamin group riboflavin 50.0mg/kg + sesamin 50.0mg/kg

The results are shown in FIG. 5. As can be seen from the figure, when sesamin was 50mg/kg and riboflavin was 10mg/kg, no synergistic effect was exhibited between sesamin and riboflavin. To explain that the synergistic effect is desired, the total amount of sesamins should be less than 5.0 by weight relative to 1 by weight of the total amount of riboflavin converted to riboflavin.

Example 5 formulation example

(preparation example 1) granules

Sesamin 0.01g

Vitamin B₂ 0.01g

0.25g of vitamin E acetate

Silica 20.5g

Corn starch 179.0g

Mixing the above powders uniformly, adding 100ml 10% hydroxypropyl cellulose-ethanol solution, kneading, extruding, and drying according to conventional method to obtain granule.

(preparation example 2) capsules

Gelatin 60.0%

30.0 percent of glycerin

0.15 percent of methyl p-hydroxybenzoate

Propyl p-hydroxybenzoate 0.51%

Proper amount of water

The soft capsule film containing the above components was filled with the following composition according to a conventional method to obtain 1 soft capsule of 200 mg.

Sesamin 10.0mg

Vitamin B₂ 1.0mg

Glycerin fatty acid ester 15.0mg

Beeswax 15.0mg

Wheat germ oil 250mg

(preparation example 3) tablet

Sesamin 0.01g

Vitamin B₂ 0.1g

Starch 282g

Sucrose fatty acid ester 9.0g

Silica 9.0g

Mixing the above materials, tabletting with single-punch tablet press to obtain tablet with diameter of 9mm and weight of 300mg

The tablet of (4).

Preparation example 4 health drink

Flavor development: DL-sodium tartrate 0.1g

Succinic acid 0.009g

Sweet taste: liquid sugar 800g

Sour taste: citric acid 12g

Vitamins: vitamin C10 g

Sesamin 1g

Vitamin B₂ 3g

Vitamin E3 g

Cyclodextrin 5g

Spice 15ml

Potassium chloride 1g

Magnesium sulfate 0.5g

The above ingredients were mixed and water was added to 10 liters. The health beverage is administered 1 time at a dose of 100 ml.

(preparation example 5) tablet

Vitamin B₂ 0.1g

280g of starch

Hydroxypropyl cellulose 2.0g

Silica 10.0g

The above materials were mixed and compressed by a single punch tablet press to prepare tablets having a diameter of 8mm and a weight of 250 mg.

Preparation example 6 health drink

Fructose glucose solution 1.1kg

Lemon juice 40g

Citric acid 5g

Vitamin B20.2g

Caffeine 5g

Cyclodextrin 5g

Perfume 5g

The above ingredients were mixed and water was added to 10 liters. The health beverage is administered 1 time at a dose of 100 ml.

The composition of the present invention containing riboflavin and sesamins is safe for humans, animals and the like because the composition of the present invention synergistically exerts the effects of physiological activities of riboflavin, for example, an analgesic effect and an anti-fatigue effect, and is therefore continuously ingested by the administration of sesamins in combination.

Claims (11)

1. A composition comprising riboflavin or a riboflavin derivative and sesamin selected from the group consisting of sodium riboflavin phosphate, flavin mononucleotide, riboflavin tetrabutyl ester and/or riboflavin phosphate, wherein the ratio of the total amount of sesamin selected from sesamin, episesamin, sesamol, episesamin and/or sesamolin is 4.5 or less by weight when the equivalent of riboflavin or riboflavin derivative is 1.

2. The composition according to claim 1, wherein the sesamin component is contained in an amount of 1 to 200mg per 1 day.

3. The composition according to claim 1 or 2, wherein the sesamin component is a sesamin component concentrate containing 1% by weight or more of sesamin component.

4. The composition according to claim 1 or 2, wherein the sesamin-like substance is sesamin and/or episesamin.

5. The composition of claim 1 or 2, wherein the riboflavin derivative is any one of riboflavin sodium phosphate or riboflavin tetrabutyl ester.

6. The composition of claim 4, wherein the riboflavin derivative is any one of riboflavin sodium phosphate or riboflavin tetrabutyl ester.

7. The composition of claim 1 or 2, which is a composition for oral administration.

8. Use of riboflavin or a riboflavin derivative and sesamin in the manufacture of a composition for relieving pain, wherein the ratio of the total amount of sesamin selected from sesamin, episesamin, sesamol, episesamin and/or sesamolin is 4.5 or less by weight when the equivalent of riboflavin or riboflavin derivative is 1, and the riboflavin derivative is selected from riboflavin sodium phosphate, flavin mononucleotide, riboflavin tetrabutyl ester and/or a monodiethanolamine salt of riboflavin phosphate.

9. Use of riboflavin or a riboflavin derivative and sesamin in the manufacture of an anti-fatigue composition, wherein the total amount of sesamin selected from sesamin, episesamin, sesamol, episesamin and/or sesamolin is 4.5 or less by weight ratio when the equivalent of riboflavin or a riboflavin derivative is 1, and the riboflavin is selected from riboflavin sodium phosphate, flavin mononucleotide, riboflavin tetrabutyl and/or a monodiethanolamine salt of riboflavin phosphate.

10. Use of sesamins in the manufacture of a composition for oral administration comprising riboflavin or a riboflavin derivative, wherein the sesamins are selected from sesamin, episesamin, sesamol, episesamin and/or sesamolin in a ratio of total amounts of sesamins in a weight ratio of 4.5 or less at an equivalent of 1 of riboflavin or a riboflavin derivative selected from sodium riboflavin phosphate, flavin mononucleotide, riboflavin tetrabutyl ester and/or a monodiethanolamine salt of riboflavin phosphate.

11. Use of sesamins selected from sesamin, episesamin, sesamol, episesamin and/or sesamolin in a ratio of 4.5 or less by weight in total for the production of a composition for enhancing the physiological activity of riboflavin comprising riboflavin or a riboflavin derivative selected from riboflavin sodium phosphate, flavin mononucleotide, riboflavin tetrabutyl ester and/or a monodiethanolamine salt of riboflavin phosphate, wherein the ratio of the total amount of sesamins is 4.5 or less, when the equivalent of riboflavin or riboflavin derivative is 1.