Motor function improver

Abstract

The present invention addresses the problem of providing a medicine and a food composition for improving motor function. The present invention relates to a motor function improver comprising a combination of (a) one or more components selected from febuxostat and topiroxostat and (b) inosine.

Description

Motor function enhancers

[0001] The present invention relates to medicines and foods that improve motor function.

[0002] An increasing number of people are experiencing symptoms such as decreased motor function, decreased stamina, and fatigue due to aging, long-term hospitalization, prolonged restrictions on movement, etc. At the same time, an increasing number of people are hoping to further improve their current motor skills and endurance.

[0003] Frailty, locomotive syndrome, sarcopenia, and muscular dystrophy are well-known examples of diseases that impair motor function. Sarcopenia is defined as a decline in skeletal muscle mass due to aging, with secondary declines in muscle strength and aerobic capacity. A decrease in muscle mass is essential for sarcopenia, and a diagnosis is made when either muscle strength or physical performance is also present. It has been pointed out that portion-restricting diets increase the risk of sarcopenia. Muscular dystrophy is a general term for genetic muscle disorders in which muscle fiber destruction, degeneration (myo-necrosis), and regeneration occur repeatedly, gradually leading to progressive muscle atrophy and muscle weakness. Frailty refers to a fragile state (an intermediate stage) that is prone to health problems, such as unintended weakness, decreased muscle strength, decreased activity, and decreased mental activity, in the process of elderly people becoming dependent on care. Locomotive syndrome refers to a condition in which the physical ability to stand and walk (mobility function) is impaired due to musculoskeletal disorders (also known as locomotor syndrome or musculoskeletal syndrome).

[0004] As ingredients that improve motor function, substances derived from Euglena, soyasaponins, butyric acid bacteria, lactic acid bacteria, bifidobacteria, globin protein hydrolysates, etc. have been reported (Patent Documents 1 to 5).

[0005] JP 2019-024481 A International Publication No. 2019 / 208627 Specification JP 2021-121584 A JP 2022-164021 A JP 2023-048160 A

[0006] However, the effects of conventional motor function enhancers are insufficient, and the development of new medicines and foods that improve motor function is desired. An object of the present invention is to provide medicines and food compositions that improve motor function.

[0007] Therefore, the present inventors evaluated the endurance of mice using a treadmill, and assessed the changes in endurance and muscle AMP, ADP, and ATP levels after running for a certain period of time. Furthermore, using SAMP8 strain mice, which are model animals for sarcopenia and frailty, the inventors evaluated the endurance, muscle weight, changes in muscle AMP, ADP, and ATP levels, and motor control function after continuous administration. They found that the combined use of febuxostat or topiroxostat with inosine provides excellent effects for improving athletic ability and motor control function, and can improve the symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy, and thus completed the present invention.

[0008] That is, the present invention provides the following inventions [1] to

[20] . [1] A motor function improver comprising a combination of (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine. [2] A motor function improver comprising (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine. [3] A symptom-improving agent for frailty, locomotive syndrome, sarcopenia, or muscular dystrophy comprising a combination of (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine. [4] A symptom-improving agent for frailty, locomotive syndrome, sarcopenia, or muscular dystrophy comprising (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine. [5] A food composition for improving motor function, comprising a combination of (a) one or more selected from febuxostat and topiroxostat and (b) inosine. [6] A food composition for improving motor function, comprising (a) one or more selected from febuxostat and topiroxostat and (b) inosine. [7] A food composition for improving the symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy, comprising a combination of (a) one or more selected from febuxostat and topiroxostat and (b) inosine. [8] A food composition for improving the symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy, comprising (a) one or more selected from febuxostat and topiroxostat and (b) inosine. [9] A combination of (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine, used to improve motor function.

[10] A composition containing (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine, used to improve motor function.

[11] A combination of (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine, used to improve symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy.

[12] A composition containing (a) one or more selected from febuxostat and topiroxostat and (b) inosine, used for improving the symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy.

[13] A combination of (a) one or more selected from febuxostat and topiroxostat and (b) inosine, for the manufacture of a motor function enhancer.

[14] A composition containing (a) one or more selected from febuxostat and topiroxostat and (b) inosine, for the manufacture of a motor function enhancer.

[15] A combination of (a) one or more selected from febuxostat and topiroxostat and (b) inosine, for the manufacture of an agent for improving the symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy.

[16] A composition comprising (a) one or more selected from febuxostat and topiroxostat and (b) inosine for the manufacture of an agent for improving symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy.

[17] A method for improving motor function, characterized by administering a combination of (a) one or more selected from febuxostat and topiroxostat and (b) inosine.

[18] A method for improving motor function, characterized by administering a composition comprising (a) one or more selected from febuxostat and topiroxostat and (b) inosine.

[19] A method for improving symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy, characterized by administering a combination of (a) one or more selected from febuxostat and topiroxostat and (b) inosine.

[20] A method for improving symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy, comprising administering a composition containing (a) one or more selected from febuxostat and topiroxostat, and (b) inosine.

[0009] Administration of (a) one or more compounds selected from febuxostat and topiroxostat in combination with (b) inosine improves motor function. Therefore, it is possible to improve the motor function of people suffering from symptoms such as decreased motor ability, decreased endurance, and fatigue due to aging, long-term hospitalization, prolonged activity restriction, etc. It is also possible to improve the motor function of healthy individuals who wish to improve their motor function. Furthermore, it is also possible to improve symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy.

[0010]

[0046] In a study using C57BL6j mice, the effects on endurance (number of electrical stimulations during running) of a febuxostat alone administration group (Feb5), an inosine alone administration group (Ino25), and a febuxostat and inosine combined group (Feb+Ino) are shown. In a study using C57BL6j mice, the effects on average running time and running distance of a febuxostat and inosine combined group (Feb+Ino) are shown. In a study using C57BL6j mice, the effects on endurance (number of electrical stimulations during running) of a febuxostat and inosine combined group (Feb+Ino) during a 20-minute exercise load are shown. In a study using C57BL6j mice, the effects on average running time and running distance of a febuxostat and inosine combined group during a 20-minute exercise load are shown. 1 shows the effects of a 20-minute exercise load on ATP, ADP, and AMP levels in muscles (tibialis anterior and extensor digitorum longus) in a group administered a combination of febuxostat and inosine in a study using C57BL6j mice. 2 shows the incline, speed, distance, and administration schedule of a treadmill device in a study using SAMP8 mice. 3 shows the change in maximum running distance after continuous administration in a control group (MC: methylcellulose administration group) and a group administered febuxostat and inosine (administration group). 4 shows the change in weight of fast-twitch and mixed muscles after continuous administration in a control group (methylcellulose (MC) administration group) and a group administered febuxostat and inosine (FI group) in a study using SAMP8 mice. Figure 1 shows changes in adenine nucleotide levels in skeletal muscle after continuous administration in a control group (methylcellulose (MC)-administered group) and a group administered with febuxostat and inosine (medication group) in a study using SAMP8 mice. Figure 2 shows changes in the holding duration at a constant speed, the sustainable holding speed in acceleration mode, and the holding duration in acceleration mode after continuous administration in a control group (methylcellulose (MC)-administered group) and a group administered with febuxostat and inosine (FI group) in a study using SAMP8 mice.

[0011] As used herein, "improving motor function" is not particularly limited to specific embodiments, but includes embodiments in which athletic ability is maintained or improved by improving or suppressing a decline in endurance that enables sustained exercise under aerobic or anaerobic exercise, increasing the amount of exercise, improving or suppressing a decline in muscle function (muscle strength), suppressing muscle fatigue, and increasing muscle contractile force. It also includes embodiments in which weight loss or visceral fat mass is achieved by maintaining or improving athletic ability. Improvements in motor function include embodiments obtained as a result of the improvement in motor function, such as improvement in movements of daily living, prevention or amelioration of lower back pain, prevention or amelioration of muscle or joint stiffness, improved muscle or joint mobility, improved physical flexibility, and prevention of injury.

[0012] In this specification, sarcopenia is defined as a decrease in skeletal muscle mass due to aging, with secondary declines in muscle strength and aerobic exercise capacity. A decrease in muscle mass is a prerequisite for a diagnosis of sarcopenia, and a decrease in either muscle strength or physical ability is considered a diagnosis. It has been pointed out that a diet that restricts intake of food increases the risk of sarcopenia. The EWGSOP classifies sarcopenia into primary sarcopenia, which occurs with aging, and secondary sarcopenia, which occurs due to activity, nutrition, or disease. Primary age-related sarcopenia has no clear cause other than aging. Secondary sarcopenia is classified into three types: (1) Activity-related sarcopenia, which can be caused by being bedridden, an inactive lifestyle, ataxia, or weightlessness; and (2) Disease-related sarcopenia, which is associated with severe organ failure (heart, lung, liver, kidney, brain), inflammatory disease, malignant tumor, or endocrine disease. (3) Nutrition-related: Inadequate energy and / or protein intake due to malabsorption, gastrointestinal disorders, and medications that cause anorexia.

[0013] As used herein, muscular dystrophy is a general term for hereditary muscle diseases in which muscle fiber destruction, degeneration (muscle necrosis), and regeneration occur repeatedly, gradually leading to progressive muscle atrophy and muscle weakness. Specifically, it refers to diseases in which the primary complaint is muscle weakness and muscle atrophy and the following two conditions are met: (1) It is a hereditary disease. (2) Skeletal muscle exhibits dystrophic changes. Dystrophic changes are characterized by the loss of muscle fiber bundle structure, characterized by muscle fiber size variation, circularization, increased central nuclei, connective tissue proliferation, and fatty changes. This definition was based on the pathological findings of Duchenne muscular dystrophy, the first reported type of muscular dystrophy.

[0014] In this specification, "frailty" refers to a vulnerable state (intermediate stage) in which elderly people are prone to health problems such as unintentional weakness, decreased muscle strength, decreased activity, and decreased mental activity as they progress towards a state requiring nursing care. The evaluation index of Fried et al. is the mainstream for evaluating frailty, and a person is considered to be frail if three of the following indicators apply: 1) weight loss 2) decreased walking speed 3) decreased grip strength 4) easily fatigued 5) decreased physical activity level

[0015] Locomotive syndrome refers to a condition in which mobility is impaired due to disorders of the musculoskeletal system, and is a concept proposed by the Japanese Orthopaedic Association in 2007. It is abbreviated as "Locomo" and its Japanese name is "Musculoskeletal Syndrome." Here, the musculoskeletal system refers to the tissues and organs involved in moving the body, and is composed of bones, muscles, joints, ligaments, tendons, nerves, etc. The motor function improvement of the present invention can also improve symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy.

[0016] One aspect of the present invention is a motor function enhancer comprising a combination of (a) one or more selected from febuxostat and topiroxostat and (b) inosine. Another aspect of the present invention is a food composition for improving motor function comprising a combination of (a) one or more selected from febuxostat and topiroxostat and (b) inosine. Another aspect of the present invention is an improvement in the symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy comprising a combination of (a) one or more selected from febuxostat and topiroxostat and (b) inosine. Another aspect of the present invention is a food composition for improving the symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy comprising a combination of (a) one or more selected from febuxostat and topiroxostat and (b) inosine.

[0017] Component (a), one of the active ingredients of the motor function improving agent and motor function improving food composition of the present invention, is one or more selected from febuxostat and topiroxostat. Febuxostat is a compound with the chemical name 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid. Topiroxostat is a compound with the chemical name 4-[5-(4-pyridinyl)-1H-1,2,4-triazol-3-yl]-2-pyridinecarbonitrile. These compounds suppress uric acid production by selectively inhibiting xanthine oxidase without affecting the activity of purine / pyrimidine metabolic enzymes. Therefore, these components are commercially available as agents for treating hyperuricemia. Furthermore, these components are known to be clearly different from allopurinol in that they do not affect the activity of purine / pyrimidine metabolic enzymes. These components can be produced by known methods, for example, as described in Japanese Patent Nos. 2725886 and 3600832, and are also available as commercially available products.

[0018] Another active ingredient (b) of the motor function improving agent and motor function improving food composition of the present invention is inosine. Inosine is an N-riboside composed of hypoxanthine and D-ribose. Inosine can also be produced by known methods and is commercially available.

[0019] As described in the Examples below, the combination of component (a) and component (b) was used to evaluate the endurance of mice using a treadmill, and the changes in endurance and muscle AMP, ADP, and ATP levels during a certain period of running were evaluated.Compared to the single administration of component (a) or component (b), it was found that significantly superior endurance and athletic performance were improved.In addition, the combined group showed a significant increase in muscle AMP and ADP, but no change in ATP.Using SAMP8 strain mice, a model animal of sarcopenia and frailty, the endurance improvement effect, muscle weight, changes in muscle AMP, ADP, and ATP levels, and motor control function (rotating rod holding test) after continuous administration were evaluated.It was found that the combined group of component (a) and component (b) showed excellent endurance improvement effects, increased muscle weight, increased ATP materials such as AMP and IMP in the muscles, and improved motor control function. Here, SAMP8 mice are naturally accelerated aging mice, and because skeletal muscle mass and muscle strength decline naturally, they are suitable as a sarcopenia model. They are also suitable as a frailty model because they exhibit declines not only in muscle strength but also in cognitive, immune, and metabolic functions. Therefore, the combination of component (a) and component (b) has the effect of improving endurance and athletic performance, making them excellent as motor function enhancers and food compositions for improving motor performance. The motor function enhancers and food compositions for improving motor performance of the present invention maintain or improve athletic performance by improving or suppressing declines in endurance, enabling sustained aerobic or anaerobic exercise, increasing exercise volume, improving or suppressing declines in muscle function (muscle strength), suppressing muscle fatigue, and enhancing muscle contractility. Furthermore, maintaining or improving athletic performance leads to weight loss or a decrease in visceral fat mass. Furthermore, the improvement of motor function includes functions obtained as a result of the improvement of motor function, such as improvement of movements in daily life, prevention or improvement of lower back pain, prevention or improvement of muscle or joint stiffness, improvement of muscle or joint mobility, improvement of body flexibility, prevention of injury, etc. Furthermore, a combination of one or more selected from (a) febuxostat and topiroxostat and (b) inosine is useful for improving symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy.

[0020] The motor function enhancer, motor function enhancing food composition, symptom-improving agent for frailty, locomotive syndrome, sarcopenia, or muscular dystrophy, and symptom-improving food composition for frailty, locomotive syndrome, sarcopenia, or muscular dystrophy of the present invention are each a combination of the aforementioned components (a) and (b), and may be in any form that allows for the combined use of these components. Specifically, based on the preferred administration form and administration schedule of each component, each component may be formulated separately into its own dosage form, or may be formulated together into a single dosage form (i.e., formulated as a combination preparation). Furthermore, each formulation may be manufactured and sold together in a single package suitable for use in combination, or each formulation may be manufactured and sold separately in separate packages. When each formulation is packaged in a single package or in separate packages, it can also be made into a kit formulation that includes instructions for use describing the combined administration of components (a) and (b). Here, the "instructions" may be any that describe the dosage. Specific examples include package inserts, pamphlets, etc. Furthermore, the kit preparation including the instruction manual may be one in which the instruction manual is printed or attached to the package of the kit preparation, or one in which the instruction manual is enclosed in the package of the kit preparation together with the motor function enhancer, motor function enhancing food composition, agent for improving symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy, and food composition for improving symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy of the present invention. The motor function enhancer, motor function enhancing food composition, agent for improving symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy, and food composition for improving symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy of the present invention are preferably in a form containing the above-mentioned component (a) and component (b).

[0021] The content ratio or blending ratio of component (a) to component (b) in the motor function improver, motor function improver food composition, symptom-improving agent for frailty, locomotive syndrome, sarcopenia or muscular dystrophy, and symptom-improving food composition for frailty, locomotive syndrome, sarcopenia or muscular dystrophy of the present invention is preferably 1:20 to 20:1, and more preferably 1:10 to 10:1, in mass ratio (a:b).

[0022] The administration forms of the motor function improver and the symptom-improving agent for frailty, locomotive syndrome, sarcopenia, or muscular dystrophy of the present invention include, for example, oral administration using tablets, capsules, granules, powders, syrups, etc., or parenteral administration using injections, suppositories, inhalants, transdermal absorbents, topical preparations, etc. To prepare such various dosage forms, the components (a) and (b) can be used alone or in appropriate combination with other pharmaceutically acceptable excipients, binders, fillers, disintegrants, surfactants, lubricants, dispersants, buffers, preservatives, flavoring agents, fragrances, coating agents, carriers, diluents, etc. Among these administration forms, oral administration is preferred, and oral liquid formulations can be prepared by conventional methods by adding flavoring agents, buffers, stabilizers, etc.

[0023] The food composition for improving motor function and the food composition for improving the symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy of the present invention may take the form of various foods such as food and beverages such as milk, processed milk, milk drinks, yogurt, soft drinks, tea drinks, coffee drinks, fruit juice drinks, carbonated drinks, juice, jelly, wafers, biscuits, bread, noodles, sausages, and nutritional foods, as well as functional foods, nutritional supplements, and specific nutritional supplements in the same form as the oral administration formulations described above (tablets, capsules, syrup, etc.).

[0024] To prepare food compositions of various forms, the components (a) and (b) can be incorporated into the food for improving motor function either alone or in appropriate combination with other food ingredients, solvents, softeners, oils, emulsifiers, preservatives, flavorings, stabilizers, colorants, antioxidants, moisturizers, thickeners, etc.

[0025] The dosage or intake of the motor function improving agent, motor function improving food composition, symptom-improving agent for frailty, locomotive syndrome, sarcopenia or muscular dystrophy, and symptom-improving food composition for frailty, locomotive syndrome, sarcopenia or muscular dystrophy of the present invention can be selected appropriately depending on various conditions such as the age and weight of the subject. For example, in the case of oral administration, the total amount of component (a) and component (b) can be 1 mg to 1000 mg per day, administered in divided doses approximately once to three times a day.

[0026] The present invention will now be described in more detail with reference to examples, but the present invention is not limited to these examples.

[0027] Example 1: The effects of test compounds on the running endurance of mice were evaluated using a treadmill. Eighteen C57BL6j mice (11-13 week old males) were used. The mice were divided into groups: 5 mice in the methylcellulose (MC) group, 3 mice in the febuxostat (Feb) group, 3 mice in the inosine group, and 7 mice in the febuxostat + inosine (Feb + Ino) group. The treadmill used was an LE8700RTS. Running conditions were initiated at 4 m / min, increasing speed every 2 minutes until reaching a maximum speed of 20 m / min. The number of electrical stimuli administered by a device behind the running lane was recorded, and this number was used as a measure of fatigue. Running was terminated when 130 electrical stimuli were administered, and running time and distance were recorded. Running time was limited to a maximum of 80 minutes. Medication was administered via a probe 45 minutes before running. The dosage was 1 / 100 of body weight for both the MC and Feb + Ino groups. The MC group received a 0.5% methylcellulose solution, and the doses of febuxostat and inosine were adjusted to 5 mg / kg and 25 mg / kg, respectively, by dissolving them in 0.5% methylcellulose. The evaluation of endurance (number of electrical stimulations during running) is shown in Figure 1. As shown in Figure 1, the febuxostat alone administration group (Feb5) and the inosine alone administration group (Ino25) showed almost no improvement in endurance compared to the control group (MC), while the febuxostat and inosine combination group (Feb+Ino) clearly showed an improvement in endurance. The average running time and running distance of the febuxostat and inosine combination group are also shown in Figure 2.

[0028] Example 2: The effects of the test compound on endurance and intramuscular AMP, ADP, and ATP levels in mice after 20 minutes of exercise were evaluated using a treadmill. Eight C57BL6j mice (11-13 week old males) were used. The mice were divided into four groups: a methylcellulose (MC) group (4 mice) and a febuxostat + inosine (Feb + Ino) group (4 mice). The treadmill used was an LE8700RTS. Running conditions were initiated at 4 m / min, increased every two minutes, and reached a maximum speed of 20 m / min. The number of electrical stimuli administered by a device behind the running lane was recorded, and the number of stimuli was used as a measure of fatigue. Running was terminated 20 minutes after the start of the run (12 minutes at maximum speed), and the running distance and number of stimuli were recorded. If the running stimuli reached 130, the run was terminated immediately without waiting for the 20-minute period. Medication was administered orally via a sonde 45 minutes before running. The dose was 1 / 100 of body weight for both the MC and Feb+Ino groups. The MC group received 0.5% methylcellulose solution, while the doses of febuxostat and inosine were adjusted to 5 mg / kg and 25 mg / kg, respectively, dissolved in 0.5% methylcellulose. After 20 minutes of running, animals were anesthetized immediately. Within 10 minutes, the muscles (tibialis anterior and extensor digitorum longus) were removed and immediately flash-frozen in liquid nitrogen. While still frozen, the muscle tissue was crushed using a bead shocker and deproteinized with 70% acetonitrile per tissue weight. ATP, ADP, and AMP were extracted and quantitatively analyzed by HPLC. Figure 3 shows endurance performance during a 20-minute exercise load (number of electrical stimulations during running). Figure 4 shows the average running time and distance for the febuxostat and inosine combination group. Figure 4 clearly demonstrates that the febuxostat and inosine combination group (Feb+Ino) demonstrated an endurance-enhancing effect. The amounts of ATP, ADP, and AMP in the muscles (tibialis anterior and extensor digitorum longus) are shown in Figure 5. As can be seen from Figure 5, in the febuxostat and inosine combination group, there was no change in ATP compared to the control group, but ADP and AMP increased.

[0029] Example 3: Eighteen 41-week-old male SAMP8 mice were used. Nine mice were divided into a methylcellulose-administered + exercise group and nine mice were divided into a febuxostat (5 mg / kg) + inosine (25 mg / kg) + exercise group. The drug was prepared by grinding 5 mg of febuxostat in an agate mortar (for approximately 5 minutes until a film formed), adding inosine (25 mg), dissolving in 1 ml of methylcellulose, and diluting 10-fold. Ninety minutes before running, mice were administered NaHCO3 solution at 1 / 100 of their body weight. Sixty minutes before running, mice were administered methylcellulose or febuxostat + inosine-containing methylcellulose at 1 / 100 of their body weight. The same treadmill with a 10-degree incline as in Examples 1 and 2 was used. The speed, distance, and dosing schedule were as shown in Figure 6. The increase in maximum running distance, muscle weight of various skeletal muscles, and intramuscular ATP and other metabolites were measured before and after continuous administration. Furthermore, the sense of balance was evaluated by the Rotarod test.

[0030] The maximum running distance after continuous administration was significantly increased in the febuxostat and inosine-administered group (administration group) compared to the control group (MC: methylcellulose-administered group) (Figure 7). Furthermore, muscle weight after continuous administration was significantly increased in the febuxostat and inosine-administered group (FI group) compared to the control group (methylcellulose (MC)-administered group) for fast-twitch and mixed muscle (Figure 8). Furthermore, the amount of adenine nucleotides in skeletal muscle was increased in the febuxostat and inosine-administered group (administration group) compared to the control group (methylcellulose (MC)-administered group), with no change in ATP (Figure 9). Furthermore, a Rotarod test (rotating rod grasping test) was performed after the continuous administration. Compared to the control group (methylcellulose (MC)-administered group), the febuxostat and inosine-administered group (FI group) showed an increase in the grasping duration at a constant speed, the number of rotations that could be sustained while grasping in an accelerating mode, and the grasping duration in an accelerating mode (Figure 10).

Claims

1. A motor function enhancer comprising a combination of (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine.

2. A motor function enhancer containing (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine.

3. An agent for improving symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy, comprising a combination of (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine.

4. An agent for improving symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy, comprising (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine.

5. A food composition for improving motor function, comprising a combination of (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine.

6. A food composition for improving motor function, comprising (a) one or more compounds selected from febuxostat and topiroxostat, and (b) inosine.

7. A food composition for improving symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy, comprising a combination of (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine.

8. A food composition for improving symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy, comprising (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine.

9. A combination of (a) one or more selected from febuxostat and topiroxostat and (b) inosine for use in improving motor function.

10. A composition used for improving motor function, comprising (a) one or more compounds selected from febuxostat and topiroxostat, and (b) inosine.

11. A combination of (a) one or more selected from febuxostat and topiroxostat and (b) inosine, used for improving the symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy.

12. A composition containing (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine, used for improving symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy.

13. A combination of (a) one or more selected from febuxostat and topiroxostat and (b) inosine for the manufacture of a motor function enhancer.

14. A composition for producing a motor function enhancer, comprising (a) one or more compounds selected from febuxostat and topiroxostat, and (b) inosine.

15. A combination of (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine for the manufacture of an agent for improving symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy.

16. A composition comprising (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine for the manufacture of an agent for improving symptoms of frailty, locomotive syndrome, sarcopenia, or muscular dystrophy.

17. A method for improving motor function, comprising administering a combination of (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine.

18. A method for improving motor function, comprising administering a composition containing (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine.

19. A method for improving symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy, comprising administering a combination of (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine.

20. A method for improving symptoms of frailty, locomotive syndrome, sarcopenia or muscular dystrophy, characterized by administering a composition containing (a) one or more compounds selected from febuxostat and topiroxostat and (b) inosine.

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