Preventive or improving agent for neurological disorder

Abstract

To provide a preventive or improving agent for neurological disorders caused by nerve damage resulting in reduced nerve function.SOLUTION: The preventive or improving agent contains a combination of quinoa or extract thereof and gluconodeltalactone.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an agent for preventing or ameliorating nerve damage. [Background technology]

[0002] When nerve tissue is damaged, the effector organs innervated by the damaged nerves are impaired. The number of stroke patients, a typical example of neurological damage, is extremely high in Japan, at approximately 1.2 million, resulting in enormous social losses.

[0003] When nerve damage occurs due to a stroke, traffic accident, or other causes, rehabilitation is recommended to restore nerve function. However, the current rehabilitation method's effectiveness in restoring function is insufficient, and it has been reported that even after rehabilitation, patients often remain disabled or are unable to return to society. As such, there are limitations to the effectiveness of conventional rehabilitation in restoring nerve function, and there is a need for useful means that can promote the effects of rehabilitation.

[0004] Neuropathy is also a common complication of diabetes (diabetic neuropathy), which manifests as alternating constipation and diarrhea, autonomic neuropathy (e.g., erectile dysfunction, dizziness, and abnormal sweating), and sensory neuropathy (e.g., numbness and abnormal sensations). These symptoms are thought to be the result of peripheral nerve fiber loss and decreased nerve function, which can cause abnormalities in various parts of the body. In many cases, subjective symptoms such as numbness and pain in the feet gradually spread to the central nerves. Without appropriate treatment, the loss of sensory nerve fibers can lead to the inability to sense pain or heat. This can result in the formation of foot ulcers, which, if left untreated, can lead to gangrene and, in the worst case, lower limb amputation, significantly reducing the patient's quality of life (QOL).

[0005] It has also been reported that neurological decline contributes to the decline in muscle function associated with aging (Non-Patent Document 1), and in Japan, which is an ultra-aged society, it is important to create technologies to improve declined neurological function and technologies to prevent decline in neurological function.

[0006] Nerve damage is often perceived as pain (neuropathic pain). Pain can cause inconvenience and discomfort in daily life, reduce motivation to work, and reduce quality of life. Neuropathic pain occurs when damaged nerves remain excited, resulting in excessive release of pain-transmitting substances from the damaged nerves. As a result, even after the cause or source of pain is removed and the disease is cured, pain may persist for a long time, be severe with slight stimulation, be felt with changes in weather or climate, or be felt even without movement. Neuropathic pain often manifests as symptoms such as electric shock-like pain or severe numbness.

[0007] Neuropathic pain is thought to be caused by calcium entering nerve cells through calcium channels, which excites the nerve cells and causes excessive release of neurotransmitters. Calcium channel blockers are often used for its treatment and prevention. Antidepressants and antiepileptic drugs may also be used. Furthermore, if pain persists with these drugs and interferes with daily activities, narcotic analgesics such as opioids may also be used.

[0008] Quinoa is a grain native to the Andes region of South America, belonging to the genus Chenopodiaceae, subfamily Chenopodiaceae, family Amaranthaceae. Quinoa seeds are known to be highly nutritious, and because they are rich in dietary fiber and polyphenols, they are known to have anti-hyperglycemic and antioxidant effects. Quinoa stem and leaf extracts have also been reported to inhibit collagenase activity and promote collagen production (Patent Document 1).

[0009] However, it is not known that quinoa is effective in improving neurological disorders. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] Japanese Patent Publication No. 2022-139538 [Non-patent literature]

[0011] [Non-Patent Document 1] Nutrition 28: 495-503, 2012 Summary of the Invention [Problem to be solved by the invention]

[0012] The present invention relates to providing an agent for preventing or ameliorating nerve disorders caused by decreased nerve function due to nerve damage. [Means for solving the problem]

[0013] The present inventors have searched for materials that improve nerve function and have found that a combination of quinoa extract and glucono-delta-lactone is effective in improving nerve function decline caused by nerve damage.

[0014] That is, the present invention relates to the following 1) to 10). 1) An agent for preventing or improving nerve disorders comprising a combination of quinoa or an extract thereof and glucono-delta-lactone. 2) A nerve regeneration promoter comprising a combination of quinoa or its extract and glucono-delta-lactone. 3) A promoter for the recovery of motor function after nerve damage, which comprises a combination of quinoa or an extract thereof and glucono-delta-lactone. 4) An agent for inhibiting muscle atrophy after nerve injury, comprising a combination of quinoa or an extract thereof and glucono-delta-lactone. 5) A preventive or ameliorative agent for neuropathic pain comprising a combination of quinoa or an extract thereof and glucono-delta-lactone. 6) A food for preventing or improving nerve disorders, comprising a combination of quinoa extract and glucono-delta-lactone. 7) A food for promoting nerve regeneration that combines quinoa extract and glucono-delta-lactone. 8) A food for promoting recovery of motor function after nerve damage, which is a combination of quinoa extract and glucono-delta-lactone. 9) A food for inhibiting muscle atrophy after nerve injury, consisting of a combination of quinoa extract and glucono-delta-lactone. 10) A food for preventing or improving neuropathic pain, comprising a combination of quinoa extract and glucono-delta-lactone. [Effects of the Invention]

[0015] According to the present invention, it is possible to provide a pharmaceutical, quasi-drug, food, or supplement for preventing or ameliorating nerve damage. According to the present invention, it is possible to promote recovery of nerve function and relieve pain associated with nerve damage using a food or supplement, and therefore it is possible to provide a new means for improving the quality of life for elderly people and patients receiving care at home due to nerve damage. [Brief explanation of the drawings]

[0016] [Figure 1] Effect on motor function after spinal cord crush injury. ***p< 0.0001 by Mann-Whitney test DETAILED DESCRIPTION OF THE INVENTION

[0017] In the present invention, "quinoa" refers to Chenopodium quinoa, a plant of the Amaranthaceae family, Chenopodiaceae subfamily, Chenopodium genus. The parts of quinoa used may be, for example, petals, corollas, flowers, inflorescences (spikes), leaves, seeds, fruits, stems, roots, or a combination thereof, but seeds are preferred. Quinoa seeds are classified into red quinoa, white quinoa, gold quinoa, black quinoa, etc. depending on their color, and red quinoa is preferred. In the present invention, the quinoa may be used as it is after drying the above-mentioned parts, or may be roasted, steam-dried, or powdered, but it is preferably used as an extract. The method for producing the quinoa extract is not particularly limited, and the extract can be obtained by extracting the above-mentioned plant parts by a known method. In the present invention, an extract produced by a solvent extraction method using various extraction solvents is preferably used.

[0018] The solvent for extraction can be either polar or nonpolar. Specific examples of solvents include water; alcohols such as methanol, ethanol, propanol, and butanol; polyhydric alcohols such as propylene glycol and butylene glycol; ketones such as acetone and methyl ethyl ketone; esters such as methyl acetate and ethyl acetate; linear and cyclic ethers such as tetrahydrofuran and diethyl ether; polyethers such as polyethylene glycol; hydrocarbons such as squalane, hexane, cyclohexane, and petroleum ether; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as dichloromethane, chloroform, and dichloroethane; and supercritical carbon dioxide; pyridines; organic solvents such as fats, oils, waxes, and other oils; and mixtures thereof. Suitable solvents include water, alcohols, and alcohol-water mixtures, with alcohol-water mixtures being more preferred. Ethanol is preferred as the alcohol. Furthermore, the alcohol-water mixture can be used by mixing at any ratio, but a mixture containing 50 to 99.9% alcohol (v / v % at 20° C.) is preferred.

[0019] The amount of extraction solvent used is not particularly limited as long as sufficient extraction efficiency is obtained, but for example, it is preferably 2 to 60 times by mass, more preferably 3 to 30 times by mass, and most preferably 5 to 15 times by mass relative to the dried quinoa. The extraction conditions are not particularly limited as long as they provide sufficient extraction efficiency. The extraction temperature is preferably 0°C or higher and below the boiling point of the solvent used, more preferably room temperature. However, higher extraction temperatures allow for shorter extraction times. The extraction period (time) is preferably 10 minutes to 1 day when extraction is performed by heating to 40°C or higher, and examples include 12 to 24 hours at 40 to 50°C, 2 to 12 hours at 50 to 60°C, 10 minutes to 10 hours at 60 to 70°C, and 10 minutes to 6 hours at 70 to 100°C. When extraction is performed at 40°C or lower, the extraction period is preferably 1 to 30 days, more preferably 3 to 21 days. For example, the extraction period includes 1 to 7 days at 40 to 30°C, 3 to 21 days at 30 to 20°C, and 21 to 30 days at 20 to 10°C. At room temperature, the extraction period is even more preferably 3 to 14 days.

[0020] The extraction means is not particularly limited, but for example, conventional means such as solid-liquid extraction, liquid-liquid extraction, maceration, decoction, percolation, reflux extraction, pressurized heating extraction, and supercritical extraction can be used.

[0021] The quinoa extract of the present invention may be a crude product, as long as it meets, for example, food and pharmaceutical acceptable standards and exhibits the effects of the present invention. Furthermore, if necessary, it can be subjected to treatments such as removal of inactive contaminants, deodorization, and decolorization using known techniques such as liquid-liquid partitioning, solid-liquid partitioning, activated carbon treatment, and ion exchange resin treatment. Furthermore, the concentration or proportion of a specific component (fraction) may be increased by appropriately combining known separation and purification methods (for example, removing fractions with a molecular weight of 10 kD or more by ultrafiltration membrane separation). Purification methods include organic solvent precipitation, centrifugation, ultrafiltration membrane separation, high performance liquid chromatography, column chromatography, etc.

[0022] In the present invention, the above extract can be used as is, or it can be diluted, concentrated, or freeze-dried to prepare a powder or paste. It can also be freeze-dried and then dissolved or diluted with a solvent commonly used in extraction, such as water, ethanol, propylene glycol, a water-ethanol mixture, a water-propylene glycol mixture, or a water-1,3-butylene glycol mixture, before use. It can also be encapsulated in vesicles such as liposomes or microcapsules.

[0023] Glucono delta lactone is an intramolecular ester formed by dehydration of one water molecule from gluconic acid. Glucono delta lactone of the quality used in the food industry can be obtained and used. In this specification, glucono delta lactone may be abbreviated as "GDL."

[0024] In the present invention, quinoa or an extract thereof and glucono-delta-lactone are used in combination (concomitant use), but the form is not limited thereto. That is, they may be used as a composition in which effective amounts of each ingredient are formulated in a single dosage form at an appropriate blending ratio as a combination drug, or as a kit in which drugs containing effective amounts of each ingredient are formulated individually and can be used simultaneously or separately at intervals, but simultaneous use is preferred.

[0025] When quinoa or an extract thereof is combined with gluconodeltalactone to form a formulation, the blending ratio can be selected appropriately depending on the material, application, or type of formulation, but is generally a mass ratio of quinoa or an extract thereof (in dry matter terms) to gluconodeltalactone of 1:0.01-100, preferably 1:0.1-10.

[0026] As shown in the Examples below, the combined use of quinoa extract and glucono-delta-lactone ameliorates motor impairment and promotes nerve regeneration in a central nervous system regeneration model (zebrafish) following spinal cord crush injury.

[0027] Zebrafish treated with spinal nerve crush injury are known as a model of central nervous system regeneration (Mayssa H. et al., Science, 354, 630-634 (2016)), and the promotion of recovery of motor function in this model indicates the promotion of central nervous system regeneration.

[0028] Therefore, the combination of quinoa or an extract thereof and glucono-delta-lactone can serve as an agent for preventing or ameliorating nerve damage, an agent for promoting nerve regeneration, an agent for promoting motor function recovery after nerve injury, an agent for inhibiting muscle atrophy after nerve injury, or an agent for preventing or ameliorating pain associated with nerve damage (neuropathic pain) (referred to as "agents for preventing or ameliorating nerve damage, etc."), and can be used to manufacture such agents for preventing or ameliorating nerve damage, etc. That is, the combination of quinoa or an extract thereof and glucono-delta-lactone of the present invention can be used for preventing or ameliorating nerve damage, promoting nerve regeneration, promoting motor function recovery after nerve injury, promoting inhibition of muscle atrophy after nerve injury, or preventing or ameliorating neuropathic pain. Here, the use may be therapeutic or non-therapeutic. "Non-therapeutic" is a concept that does not include medical procedures, i.e., a concept that does not include methods of surgery, therapy, or diagnosis on humans, and more specifically, a concept that does not include methods of surgery, therapy, or diagnosis on humans by a physician or a person under the direction of a physician.

[0029] In the present invention, "neuropathy" refers to a pathological condition in which nerve function is impaired due to damage to nerve cells and Schwann cells and oligodendrocytes that form myelin sheaths, caused by nerve damage, aging, etc., and specific symptoms include pain, loss of sensation (including numbness), tingling or burning sensation in the limbs or extremities, paresthesia, muscle weakness, muscle mass loss, motor function decline, decreased neuromuscular reflexes, convulsions, neuromuscular paralysis, and sexual dysfunction. Here, "nerve damage" mainly includes physical damage, hemorrhagic or ischemic damage to central nerves such as the trigeminal nerve, spinal cord, and nerve roots, or peripheral nerves such as the sciatic nerve and median nerve, caused by trauma, contusion, compression, etc., and is preferably physical damage. Age-related neurological dysfunction includes changes in the central nervous system, such as a decrease in motor cortex excitability and changes in cortical plasticity, and changes in the peripheral nervous system, such as a decrease in the number of axons, thinning of the myelin sheath, and fragmentation of acetylcholine receptors.

[0030] "Improvement" of neuropathy includes "prevention or treatment." "Prevention" of neuropathy means preventing or delaying the onset of neuropathy, and "treatment" means alleviating the symptoms of neuropathy or preventing or delaying the progression (worsening) of the symptoms.

[0031] "Nerve regeneration" means at least a partial reproduction of the normal developmental process in nerves, i.e., reproduction of at least one of the phenomena that occur during nerve repair or nerve development, such as cell proliferation, differentiation, and maturation (tissue regeneration), and preferably, as a result, the phenomenon of complete or partial recovery of the original nerve function (functional regeneration).

[0032] "Promoting recovery of motor function after nerve damage" means recovering from motor dysfunction (for example, motor paralysis, muscle weakness) that occurs in the region innervated by the damaged nerve following nerve damage. The nerve damage may be either peripheral nerve damage or central nerve damage, but is preferably peripheral nerve damage. The cause of the nerve damage is not particularly limited, and nerve damage caused by various factors such as trauma, compression by a cast, electrical injury, herniated disc, and stroke is applicable.

[0033] "Suppression of muscle atrophy after nerve damage" means suppression of muscle loss that occurs in the area innervated by the damaged nerve following nerve damage.

[0034] "Neuropathic pain" refers to pain caused by lesions or diseases of the somatosensory nervous system. Symptoms include burning or tingling sensations, and hypersensitivity to touch and cold. The sense of touch can also become so sensitive that even a light touch can cause pain (allodynia, hyperesthesia). Furthermore, symptoms often include pain even when at rest (spontaneous pain).

[0035] For example, neuropathic pain can be diagnosed by answering the following seven questions on a five-point scale (none (0 points), a little (1 point), some (2 points), very much (3 points), very much (4 points)), and then determining the total score (6 points or more indicates neuropathic pain) (Rinsei Gai 47:565-574, 2012). 1) Pain like being stabbed with needles 2) Electric shock-like pain 3) Burning or stinging pain 4) There is severe pain with numbness 5) Pain occurs when clothing rubs against the skin or when exposed to cold air. 6) Decreased or hypersensitive sensation in the area of ​​pain 7) Swelling or red or reddish-purple discoloration of the skin in the area of ​​pain

[0036] Major diseases that cause neuropathic pain include the above-mentioned nerve disorders or diseases that can cause nerve disorders, such as, but not limited to, herniated disc, low back pain, entrapment neuropathy, sciatica, trigeminal neuralgia, carpal tunnel syndrome, lumbar spondylolisthesis, spinal stenosis, multiple sclerosis, Guillain-Barré syndrome, sequelae of stroke, pain after herniorrhaphy, and postherpetic neuralgia.

[0037] "Amelioration" of neuropathic pain includes "prevention or treatment." "Prevention" of neuropathic pain means preventing or delaying the onset of neuropathic pain, and "treatment" means alleviating neuropathic pain or preventing or delaying the progression (worsening) of neuropathic pain.

[0038] The agent for preventing or improving nerve damage of the present invention can itself be used in various compositions, such as pharmaceuticals, quasi-drugs, or foods, that exhibit the effect of preventing or improving nerve damage, the effect of promoting nerve regeneration, the effect of promoting recovery of motor function after nerve damage, the effect of inhibiting muscle atrophy after nerve damage, or the effect of preventing or improving neuropathic pain, or can be used as a material or formulation to be incorporated into these. The above foods (also referred to as "foods for preventing or improving nerve disorders caused by nerve damage or aging," "foods for promoting nerve regeneration," "foods for promoting recovery of motor function after nerve damage," "foods for inhibiting muscle atrophy after nerve damage," and "foods for preventing or improving neuropathic pain") include not only general foods and beverages, but also foods labeled as such, functional foods, foods for the sick, foods for specified health uses, foods with functional claims, and supplements, as needed.

[0039] The pharmaceuticals (including quasi-drugs) containing the active ingredient of the present invention can be administered in any dosage form, but oral administration is preferred. When administered, the active ingredient can be mixed with a solid or liquid pharmaceutical non-toxic carrier suitable for administration methods such as oral administration, rectal administration, or injection, and administered in the form of a conventional pharmaceutical formulation.

[0040] Examples of such formulations include solid formulations such as tablets, granules, powders, and capsules, liquid formulations such as solutions, suspensions, and emulsions, and freeze-dried formulations. These formulations can be prepared by conventional pharmaceutical means by appropriately adding conventional additives such as stabilizers, wetting agents, emulsifiers, binders, isotonicity agents, and excipients.

[0041] The food containing the active ingredient of the present invention may take the form of various foods and beverages, such as soft drinks, tea drinks, coffee drinks, fruit juice drinks, carbonated drinks, jellies, wafers, biscuits, uncooked cereals, cooked cereals, bread, noodles, sausages, and nutritional foods, as well as nutritional supplement compositions in the same form as the oral preparations described above (solid preparations such as tablets, capsules, and lozenges). Of these, heat-processed cereals and tablets are preferred. Various forms of food products can be prepared using the active ingredient of the present invention alone or in appropriate combination with other food ingredients, solvents, softeners, oils, emulsifiers, preservatives, flavorings, stabilizers, colorants, antioxidants, moisturizers, thickeners, etc.

[0042] The content of quinoa or an extract thereof in the above composition (e.g., pharmaceutical, quasi-drug, food) varies depending on the form of use, but is preferably 1% by mass or more, more preferably 10% by mass or more, and preferably 99% by mass or less, more preferably 90% by mass or less, and also preferably 1 to 99% by mass, more preferably 10 to 90% by mass, calculated as the dried substance (e.g., dried substance dried in the sun for 1 to 1.5 weeks).

[0043] The content of glucono-delta-lactone in the above composition (e.g., pharmaceuticals, quasi-drugs, foods) varies depending on the form of use, but is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and preferably 50% by mass or less, more preferably 5% by mass or less, and also preferably 0.01 to 10% by mass, more preferably 0.1 to 5% by mass.

[0044] The dosage or intake of the above-mentioned composition (e.g., pharmaceutical, quasi-drug, food) may vary depending on the subject's condition, weight, sex, age, and other factors. However, in the case of oral administration or intake, the amount of quinoa per adult (60 kg body weight) per day, calculated on dry matter, is preferably at least 1 g, more preferably at least 10 g, and preferably not more than 1,000 g, more preferably not more than 50 g, or preferably 1 to 1,000 g, more preferably 10 to 50 g. The amount of quinoa extract per day, calculated on dry matter, is preferably at least 0.1 g, more preferably at least 1 g, and preferably not more than 50 g, more preferably not more than 10 g, or preferably 0.1 to 50 g, more preferably 1 to 10 g. The amount of glucono-delta-lactone per day is preferably 0.5 mg or more, more preferably 1 mg or more, and preferably 60 mg or less, more preferably 20 mg or less, and is preferably 0.5 to 60 mg, more preferably 1 to 20 mg.

[0045] Subjects to whom the preventive or ameliorative agent of the present invention for nerve damage may be ingested or administered include, for example, people who have decreased nerve function and have developed various symptoms of nerve damage (sensation loss, paresthesia, muscle weakness, decreased neuromuscular reflexes, convulsions, neuromuscular paralysis, etc.), people who wish to maintain or improve nerve function, and people who have developed or are at risk of developing various symptoms of neuropathic pain (burning pain or tingling sensation in the buttocks, thighs, shins, calves, knees, ankles, toes, elbows, fingers, shoulders, back, waist, etc., allodynia, hyperesthesia, etc.).

[0046] In relation to the above-described embodiment, the present invention further discloses the following aspects.

[0047] <1> An agent for preventing or improving nerve disorders comprising a combination of quinoa or an extract thereof and glucono-delta-lactone. <2> A nerve regeneration promoter comprising a combination of quinoa or an extract thereof and glucono-delta-lactone. <3> A promoter for recovery of motor function after nerve damage, comprising a combination of quinoa or an extract thereof and glucono-delta-lactone. <4> An agent for inhibiting muscle atrophy after nerve injury, comprising a combination of quinoa or an extract thereof and glucono-delta-lactone. <5> An agent for preventing or ameliorating neuropathic pain comprising a combination of quinoa or an extract thereof and glucono-delta-lactone. <6> A food for preventing or improving nerve disorders, comprising a combination of quinoa extract and glucono-delta-lactone. <7> A food for promoting nerve regeneration that combines quinoa extract and glucono-delta-lactone. <8> A food product for promoting recovery of motor function after nerve damage, which is a combination of quinoa extract and glucono-delta-lactone. <9> A food product for inhibiting muscle atrophy after nerve damage, which is a combination of quinoa extract and glucono-delta-lactone. <10> A food for preventing or improving neuropathic pain, comprising a combination of quinoa extract and glucono-delta-lactone.

[0048] <11> Use of a combination of quinoa or an extract thereof and glucono-delta-lactone for the manufacture of an agent for preventing or improving nerve disorders. <12> Use of a combination of quinoa or an extract thereof and glucono-delta-lactone for producing a nerve regeneration promoter. <13> Use of a combination of quinoa or an extract thereof and glucono-delta-lactone for the manufacture of an agent for promoting motor function recovery after nerve injury. <14> Use of a combination of quinoa or an extract thereof and glucono-delta-lactone for the manufacture of an agent for inhibiting muscle atrophy after nerve injury. <15> Use of a combination of quinoa or an extract thereof and glucono-delta-lactone for the manufacture of an agent for preventing or ameliorating neuropathic pain. <16> Use of a combination of quinoa extract and glucono-delta-lactone to produce a food for preventing or improving neurological disorders. <17> Use of a combination of quinoa extract and glucono-delta-lactone to produce a food for promoting nerve regeneration. <18> Use of a combination of quinoa extract and glucono-delta-lactone to produce a food for promoting motor function recovery after nerve injury. <19> Use of a combination of quinoa extract and glucono-delta-lactone to produce a food for inhibiting muscle atrophy after nerve injury. <20> Use of a combination of quinoa extract and glucono-delta-lactone for producing a food for preventing or ameliorating neuropathic pain.

[0049] <21> A combination of quinoa or an extract thereof and glucono-delta-lactone for preventing or ameliorating neurological disorders. <22> A combination of quinoa or an extract thereof with glucono-delta-lactone for promoting nerve regeneration. <23> A combination of quinoa or an extract thereof and glucono-delta-lactone for promoting motor function recovery after nerve injury. <24> A combination of quinoa or an extract thereof and glucono-delta-lactone for inhibiting muscle atrophy after nerve injury. <25> A combination of quinoa or an extract thereof and glucono-delta-lactone for preventing or ameliorating neuropathic pain.

[0050] <26> 1. Non-therapeutic use of quinoa or an extract thereof in combination with glucono-delta-lactone to prevent or ameliorate neurological disorders. <27> 10. Non-therapeutic use of quinoa or an extract thereof in combination with glucono-delta-lactone to promote nerve regeneration. <28> 1. Non-therapeutic use of quinoa or an extract thereof in combination with glucono-delta-lactone to promote recovery of motor function after nerve injury. <29> Non-therapeutic use of quinoa or an extract thereof in combination with glucono-delta-lactone to inhibit muscle atrophy following nerve injury. <30> 1. Non-therapeutic use of quinoa or an extract thereof in combination with glucono-delta-lactone for preventing or ameliorating neuropathic pain.

[0051] <31> A method for preventing or improving nerve disorders, which comprises ingesting or administering a combination of quinoa or an extract thereof and glucono-delta-lactone to a subject in need thereof. <32> A method for promoting nerve regeneration, comprising ingesting or administering a combination of quinoa or an extract thereof and glucono-delta-lactone to a subject in need thereof. <33> A method for promoting recovery of motor function after nerve damage, comprising ingesting or administering a combination of quinoa or an extract thereof and glucono-delta-lactone to a subject in need thereof. <34> A method for inhibiting muscle atrophy after nerve injury, comprising ingesting or administering a combination of quinoa or an extract thereof and glucono-delta-lactone to a subject in need thereof. <35> A method for preventing or ameliorating neuropathic pain, comprising ingesting or administering to a subject in need thereof a combination of quinoa or an extract thereof and glucono-delta-lactone.

[0052] <36> <1> , <6> , <11> , <16> , <21> , <26> , <31> In the above, the neuropathy is preferably a decrease in neuropathy due to a decrease in neuropathy caused by physical damage to the central or peripheral nerves. <37> <1> ~ <20> In the agent or food, the content of quinoa or an extract thereof is preferably 1% by mass or more, more preferably 10% by mass or more, and preferably 99% by mass or less, more preferably 90% by mass or less, or preferably 1 to 99% by mass, more preferably 10 to 90% by mass, calculated as the dried product (for example, dried in the sun for 1 to 1.5 weeks). <38> <1> ~ <20> In the agent or food, the content of glucono-delta-lactone is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and preferably 50% by mass or less, more preferably 5% by mass or less, or preferably 0.01 to 10% by mass, more preferably 0.1 to 5% by mass. <39> <1> ~ <35> In the above, the amount of administration or intake of a composition (e.g., a pharmaceutical, quasi-drug, food) containing quinoa or an extract thereof and glucono-delta-lactone, in the case of oral administration or intake, is preferably 1 g or more, more preferably 10 g or more, and preferably 1000 g or less, more preferably 50 g or less, or preferably 1 to 1000 g, more preferably 10 to 50 g, of quinoa, in dry matter equivalent per day, per adult (body weight 60 kg); and preferably 0.1 g or more, more preferably 1 g or more, and preferably 50 g or less, more preferably 10 g or less, or preferably 0.1 to 50 g, more preferably 1 to 10 g, of quinoa extract, in dry matter equivalent per day. <40> <1> ~ <35> In the above, the amount of administration or intake of a composition (e.g., a pharmaceutical, quasi-drug, or food) containing quinoa or an extract thereof and glucono-delta-lactone, when administered or taken orally, is preferably 0.5 mg or more, more preferably 1 mg or more, and preferably 60 mg or less, more preferably 20 mg or less, in terms of glucono-delta-lactone per adult (body weight 60 kg) per day, or preferably 0.5 to 60 mg, more preferably 1 to 20 mg. [Example]

[0053] Production Example 1 Production of quinoa extract 54.46 g of red quinoa seeds (Canada, Cana) were taken and 500 mL of 50 v / v% ethanol solution was added. After extracting at room temperature for 4 days, the extract was filtered through a cotton plug. This was concentrated under reduced pressure and then freeze-dried to obtain 3.85 g of quinoa extract powder.

[0054] Example 1: Improvement of nerve damage in a central nervous system regeneration model induced by spinal cord crush injury Six-month-old zebrafish (Danio rerio) were grouped (n=8-16) so as to be equal in weight and maximum swimming speed. 1. Sham group, control diet: (Sham) 2. Crush group, control diet: (Crush) 3. Crush group, quinoa extract + GDL diet: (Crush + quinoa extract + GDL)

[0055] The sham and spinal nerve crush (Crush) groups were fed a regular diet of Otohime (Nisshin Marubeni Feed), while the quinoa extract + GDL group was fed the same diet with quinoa extract and glucono-delta-lactone (GDL) mixed in. The wet weight ratio of quinoa extract to the total weight of the mixed diet was 3%. The animals were then freeze-dried in a freeze dryer and coated with lard at a ratio of 20% of the diet. Each animal was given 10 mg of the diet per day (5 mg twice a day, at 9:00 in the morning and 16:00 in the evening).

[0056] The GDL used was the commercially available product (model number, manufacturer) shown below. Glucono-delta-lactone (42009, Fuso Chemical Industries) In addition, the quinoa extract powder produced in Production Example 1 was used as the quinoa extract.

[0057] Spinal cord crush (SCC) was performed by making a 3mm incision with a razor at the base of the fish's dorsal fin and applying pressure with tweezers for 1 second. In the sham group, only the incision was made. After surgery, the fish were kept in a methylene blue (Nichido, approximately 6000 times diluted) solution for 3 days to prevent infection from the wound. Food was administered one week before SCC and kept until 21 days after treatment, during which time maximum swimming speed and body weight were measured as appropriate. Maximum swimming speed was measured using a flow-through exercise device (a personal tank PT-70S (Nishi-Nihon Fluid Engineering Research Co., Ltd.) modified for zebrafish experiments). After acclimatizing the fish at a speed of 1 Hz for 10 minutes, the flow rate was accelerated by 1 Hz every minute. The maximum swimming speed was defined as the speed just before the fish could no longer swim (1 Hz = 4.5 cm / sec). "No longer able to swim" refers to the state in which the fish could no longer resist the water flow and was stuck to the net downstream of the tank. Statistics were performed using t-tests or Mann-Whitney tests, with a significance level of P<0.05.

[0058] The results are shown in Figure 1. Compared to the Crush group, the group administered the quinoa extract and GDL in combination (Crush + quinoa extract + GDL group) showed an accelerated recovery of maximum swimming speed (n = 8-15 at the endpoint).

Claims

1. An agent for preventing or improving nerve disorders comprising a combination of quinoa or an extract thereof and glucono-delta-lactone.

2. A nerve regeneration promoter comprising a combination of quinoa or an extract thereof and glucono-delta-lactone.

3. A promoter for recovery of motor function after nerve damage, comprising a combination of quinoa or an extract thereof and glucono-delta-lactone.

4. An agent for inhibiting muscle atrophy after nerve injury, comprising a combination of quinoa or an extract thereof and glucono-delta-lactone.

5. An agent for preventing or ameliorating neuropathic pain comprising a combination of quinoa or an extract thereof and glucono-delta-lactone.

6. A food for preventing or improving nerve disorders, comprising a combination of quinoa extract and glucono-delta-lactone.

7. A food for promoting nerve regeneration that combines quinoa extract and glucono-delta-lactone.

8. A food product for promoting recovery of motor function after nerve damage, which is a combination of quinoa extract and glucono-delta-lactone.

9. A food product for inhibiting muscle atrophy after nerve damage, which is a combination of quinoa extract and glucono-delta-lactone.

10. A food for preventing or improving neuropathic pain, comprising a combination of quinoa extract and glucono-delta-lactone.

11. The agent according to claim 1 or the food according to claim 6, wherein the nerve disorder is a decrease in nerve function due to physical damage to the central or peripheral nerves.

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