JP2006290881A - Therapeutic agent for disturbance of motility comprising (2r)-2-propyloctanoic acid - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a drug effectively treating disturbance of motility caused by nervous function disorder, etc., accompanied with peripheral nervous diseases or spinal cord injury. <P>SOLUTION: The drug comprises (2R)-2-propyloctanoic acid, a salt, a solvate or a prodrug thereof. The drug is useful as a prophylactic, a therapeutic agent and/or a progression inhibitor for the disturbance of motility caused by peripheral neurological diseases (e.g. neuropathy, nervous function disorder caused by oppression of cauda equina nerve by spinal canal stenosis, cranial nerve palsy, diabetic peripheral nervous disorder, myasthenia gravis or muscular dystrophy), central nervous system diseases (e.g. dystonia, Huntington's disease, myelopathic muscular atrophy, spino-cerebullar degeneration, nervous function disorder accompanied with spinal cord injury or hernia of the intervertebral disk) and other symptoms and signs un-classified thereinto (e.g. peripheral neuropathic pain or dyskinesia), etc. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a therapeutic agent for motor dysfunction that is useful as a medicine.

  More specifically, (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof, or a prodrug thereof for treating motor dysfunction caused by peripheral nervous system disease or nerve dysfunction associated with spinal cord injury The present invention relates to a drug comprising

  The nervous system is roughly classified into two groups, the central nervous system and the peripheral nervous system, and the peripheral nervous system is further classified into a somatic nervous system and an autonomic nervous system. The somatic nervous system is anatomically composed of cranial nerves and spinal nerves, and functionally classified into motor nerves and sensory nerves. The basic unit of the function is called a motor unit and consists of a single motor neuron, an axon, and a collection of muscle fibers under its control.

  It is known that when this motor unit is subjected to some kind of disorder, various peripheral nervous system diseases accompanied by motor dysfunction such as muscle atrophy (skeletal muscle etc.) atrophy, weakness and exhaustion occur. Peripheral nervous system diseases are divided into neurogenic diseases, myogenic diseases and their combined diseases. Neurogenic diseases are some of the motor units from motor neurons to neuromuscular junctions. This is caused by the disorder of the limb, especially when the cell body / axon or neuromuscular junction of the motor unit is impaired, and in many cases, symptoms occur at the periphery of the extremities. For example, peripheral neuropathy such as single neuropathy / multiple neuropathy, plexus disorders, nerve root disorders degenerative spondylosis / disc herniation, spinal cord (progressive) muscular atrophy with degeneration of anterior horn cells Known are amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease in which myelin sheaths and axons are degenerated, myofass of muscle fiber bundles, myasthenia gravis due to neuromuscular junction disorder, and the like. A myogenic disease is a disease caused by a disorder of muscles (muscle fibers) itself and a disease associated therewith. In many cases, symptoms appear in the vicinity of limbs. Examples include muscular dystrophy and myopathy.

  In addition, motor dysfunction may also occur due to central nervous system diseases such as extrapyramidal disorders, system atrophy, neurodegenerative diseases, demyelinating diseases, neurological dysfunction associated with cerebrovascular diseases, and neurological dysfunction due to spinal cord injury. In addition, many other symptoms and signs considered to be motor dysfunction (for example, motor paralysis, hypertonia, involuntary movement, etc.) are known.

  However, the diseases that cause motor dysfunction as described above are diseases whose occurrence mechanism is unknown or physical damage of nerves. Targeted symptomatic treatments have been carried out, and few clinically useful drugs are known that serve as a fundamental treatment that acts directly on the impaired nervous system.

  On the other hand, neurodegenerative diseases (Alzheimer's disease, amyotrophic lateral sclerosis, progressive supranuclear palsy, olive bridge cerebellar atrophy), neurological dysfunction after stroke or cerebrospinal trauma, demyelinating diseases (multiple sclerosis, etc.) ), Brain tumor (astrocytoma, etc.), cerebrospinal disease associated with infection (meningitis, Clotsfeld-Jakob disease, AIDS dementia, etc.), Parkinson's disease, Parkinson's syndrome, etc. (2R) -2 -Propyloctanoic acid is known to be useful (see, for example, Patent Documents 1 and 2).

  These effects of (2R) -2-propyloctanoic acid have been reported to be due to the function improving action of abnormally activated astrocytes based on the action of reducing intracellular S100β content (see, for example, Non-Patent Document 1). ).

  This S100β is one of S100 proteins considered to be involved in various neurodegenerative diseases, and is present in high concentrations in glial cells and Schwann cells in the central nervous system and peripheral nervous system, as well as the pituitary gland. It is also known to exist in anterior lobe cells and Langerhans cells, and the content of S100β in cerebrospinal fluid or blood is cerebral infarction, subarachnoid hemorrhage, head trauma, various neurodegenerative diseases, after cardiopulmonary bypass surgery For example, in stroke, it is reported that measuring the blood S100 protein content is useful for diagnosis of brain lesions and neurological damage (Stroke, No. 1). 28, pages 1956-1960, 1997).

  In addition, (2R) -2-propyloctanoic acid or a salt thereof, together with a thrombolytic agent such as tissue plasminogen activator, is used to treat cerebral ischemic diseases (cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, white matter abnormality, etc.) A method for use as an agent is known (see, for example, Patent Document 3).

  Furthermore, it has been reported that administration of 2-propylpentanoic acid in a mature rat from which the axon of the sciatic nerve has been cut causes the axon to elongate and restore the motor function (see, for example, Non-Patent Document 2). ).

  However, in these patent documents and non-patent documents, (2R) -2-propyloctanoic acid treats motor dysfunction caused by peripheral nervous system disorders or motor dysfunction caused by central nervous system diseases, etc. There is no mention that it is useful.

European Patent Publication No. 06322088 European Patent Publication No. 1174131 International Publication No. 03/007992 Pamphlet Tateishi. N, 8 others, Journal of cerebral blood flow & metabolism, Vol. 22, 723-734, 2002 Xia Zhang, 6 others, Brain Research, 975, 229-236, 2003

  Currently, there are many symptomatic drugs for the treatment of motor dysfunction currently used clinically, and most of them have not reached the basic treatment even if some improvement in symptoms is observed. Therefore, development of clinically effective drugs that treat motor dysfunction by acting directly on the damaged nervous system has been eagerly desired.

  As a result of intensive studies to solve the above problems, the present inventors have surprisingly found that (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof or a prodrug thereof is The present invention was completed by discovering that it is an excellent compound for treating motor dysfunction by acting directly on the system, and further studying based on the findings.

That is, the present invention
[1] (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof, or a prodrug thereof, a preventive, therapeutic and / or progress inhibitor for motor dysfunction;
[2] The agent according to [1] above, wherein the motor dysfunction is a disorder caused by peripheral nervous system disease;
[3] Peripheral nervous system diseases are (1) peripheral nerve, cauda equina, nerve root and plexus disorders, (2) disorders of eye muscles, eye movements, regulation and refraction, (3) neurological dysfunction in inner ear diseases, (4) neurological dysfunction associated with viral infections characterized by skin and mucosal lesions, (5) neurological dysfunction associated with protozoal diseases, (6) neurological dysfunction in diabetes, (7) neurological dysfunction in metabolic disorders, (8) Neural dysfunction in thyroid disorders, (9) Neural dysfunction due to malignant neoplasms of mesothelial and soft tissues, (10) Neural dysfunction due to malignant neoplasms of cranial nerves, (11) Peripheral nerve and autonomic nervous system Neurological dysfunction due to benign neoplasm, (12) neurological dysfunction associated with head injury, (13) neurological dysfunction associated with neck injury, (14) neurological dysfunction in spinal column injury, (15) trunk and limbs Neurological dysfunction associated with injury, (16) soft tissue disorder, (17) inflammatory polyarthropathy, (18) neurological dysfunction associated with trauma at birth, (19) autonomic nervous system disorder, (20) neuromuscular The agent according to [2] above, which is one or more diseases selected from a disease at a junction, (21) paralytic syndrome, (22) muscle disease, and (23) systemic connective tissue disorder;
[4] Peripheral nervous system diseases are single neuropathy, polyneuropathy, hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease, Degelin-Sota disease, inflammatory polyneuropathy, Guillain-Barre syndrome, trigeminal nerve disorder, tongue Sore throat, facial neuropathy, painful tics, postherpetic neuralgia, neuralgic muscular atrophy, phantom limb pain, acute brachial neuritis, acute brachial plexitis, brachial plexus disorder, thoracic outlet compression syndrome, disc herniation Nerve dysfunction caused by compression of nerve roots and plexus due to spinal cord, nerve dysfunction caused by compression of caudadial nerve due to spinal stenosis, cranial nerve palsy, diabetic peripheral neuropathic pain, nerve dysfunction associated with spinal cord injury, sciatica, peripheral nervous system Childbirth injury, hereditary sensory autonomic neuropathy, myasthenia gravis, neonatal myasthenia gravis, congenital myasthenia Myasthenia gravis syndrome, addictive neuromuscular transmission disorder due to drugs or toxins, Eaton-Lambert syndrome, generalized ankylosing syndrome, motor paralysis, muscular dystrophy, channelopathy, myopathy, multisystem encephalomyopathy, progressive external The agent according to the above-mentioned [2], which is one or more diseases selected from ocular palsy, Kearns-Sayer syndrome, mitochondrial encephalomyopathy, dermatomyositis and polymyositis;
[5] The agent described in [1] above, wherein the motor dysfunction is a disorder caused by a central nervous system disease;
[6] Central nervous system diseases are (1) extrapyramidal disorders and abnormal movement, (2) system atrophy, (3) neurodegenerative diseases, (4) demyelinating diseases, (5) interstitial and seizures Disorders, (6) cerebral palsy, (7) neurological dysfunction due to inflammatory diseases of the central nervous system, (8) neurological dysfunction due to viral infection of the central nervous system, (9) a central feature characterized by skin and mucosal lesions Neurological dysfunction due to viral infection of the nervous system, (10) neurological dysfunction due to tuberculosis, (11) neurological dysfunction due to infection that takes a sexual transmission mode, (12) neurological dysfunction due to protozoal diseases of the central nervous system, (13) Neural dysfunction in nutritional deficiencies, (14) Neural dysfunction due to malignant neoplasms or secondary malignant neoplasms of the brain and central nervous system, (15) Neural dysfunction due to benign neoplasms of the central nervous system, (16 ) Accompanied by cerebrovascular disease Neurological dysfunction, (17) central nervous system neurological dysfunction associated with head injury, (18) central nervous system neurological dysfunction in spinal column disorders, (19) nerves associated with pregnancy related central nervous system maternal disorders Dysfunction, (20) neurological dysfunction of the central nervous system due to trauma during childbirth, (21) neurological dysfunction caused by drug, drug and biological product poisoning and / or its sequelae and (22) medicinal use The agent according to the above item [5], which is one or more diseases selected from a toxic effect of a non-main substance and / or a neurological dysfunction caused by a subsequent or sequelae thereof;
[7] Central nervous system disease is dystonia, abnormal movement, periodic limb movement disorder, restless leg syndrome, myoclonus, chorea-ataxia, tic, athetosis, choreoathetosis, hemiparism, Huntington's disease, hereditary ataxia , Spinal muscular atrophy, motor neuron disease, primary lateral sclerosis, progressive bulbar paralysis, progressive pseudospherical paralysis, paraneoplastic syndrome, spinocerebellar degeneration, Friedreich ataxia, multisystem atrophy Disease, Maccard Joseph disease, Shy-Drager syndrome, late-onset cerebellar cortical atrophy, erythrocytic red nucleus pallidal atrophy, Tay-Sachs disease, subacute association spinal degeneration, leukodystrophy, spasticity Cerebral palsy, paralytic or non-paralytic acute gray leukomyelitis, subacute sclerosing panencephalitis, neurological dysfunction due to Coxsackie virus infection, enterovirus infection The agent according to the above item [5], which is one or more diseases selected from neurological dysfunction caused by cerebral dysfunction, neurological dysfunction caused by compression of the cauda equina due to spinal canal stenosis, neurological dysfunction associated with spinal cord injury, and disc herniation;
[8] Motor dysfunction (1) Numbness, pain and neuropathic pain, (2) Symptoms and signs related to nervous and musculoskeletal systems, (3) Symptoms and signs related to skin and subcutaneous tissue, (4) Conversation and Symptoms and signs related to speech, (5) symptoms and signs related to recognition, perception, emotional state and behavior, and (6) behavioral and emotional disorders that develop in childhood, childhood and adolescence The agent according to [1] above, which is
[9] Motor dysfunction is acute postoperative pain, postoperative pain syndrome, chronic intractable pain, peripheral neuropathic pain, cancer pain, neuropathic pain syndrome, painful traumatic mononeuropathy, painful polyneuropathy One or more diseases selected from disorders, diabetic peripheral neuropathic pain, central pain syndrome, complex local pain syndrome, reflex sympathetic dystrophy, burning pain, phantom limb pain, abnormal involuntary movements, dyskinesia and ataxia An agent according to [1] above;
[10] The preceding item for oral administration, wherein the dose of (2R) -2-propyloctanoic acid, its salt, its solvate or their prodrug per administration is about 50 mg to about 1500 mg [1] The agent according to [1];
[11] The agent described in [10] above, wherein (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof or a prodrug thereof is administered for 1 day to about 1 year;
[12] The dose of (2R) -2-propyloctanoic acid, salt, solvate or prodrug thereof per dose is about 0.5 mg to about 25 mg per kg body weight The agent according to the aforementioned item [1] for intravenous administration;
[13] The agent described in [12] above, wherein (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof or a prodrug thereof is administered for 1 day to about 10 days;
[14] Prevention, treatment and prevention of motor dysfunction in mammals, comprising administering an effective amount of (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof or a prodrug thereof to the mammal And / or [15] (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof, or a prodrug thereof for the prevention, treatment and / or production inhibition of motor dysfunction Related to the use of

  In the present specification, motor dysfunction means “motor dysfunction caused by peripheral nervous system disease”, “motor dysfunction caused by central nervous system disease” and “symptoms and signs of other motor dysfunctions that cannot be classified into them” "Is included.

  In this specification, peripheral nervous system diseases that cause motor dysfunction include “neuropathy (mono (mono) neuropathy, multiple neuropathy)”, “peripheral nerves other than neuropathy, cauda equina, nerve root and plexus disorders. ”,“ Impaired eye muscles, eye movements, regulation and refraction ”,“ neural dysfunction in inner ear diseases ”,“ neurological dysfunction associated with viral infections characterized by skin and mucosal lesions ”,“ nerve associated with protozoal diseases ” Dysfunction, neurological dysfunction in diabetes, neurological dysfunction in metabolic disorders, neurological dysfunction in thyroid disorders, neurological dysfunction due to malignant neoplasms of mesothelial and soft tissues, olfactory nerve, Neural dysfunction due to malignant neoplasms of other cranial nerves such as optic nerve, auditory nerve "," benign neoplasms of other parts of cranial nerves, peripheral nerve and autonomic nervous system " Neurological dysfunction due to head injury, neurological dysfunction associated with neck injury, neurological dysfunction due to spinal injury, neurological dysfunction associated with thorax injury, abdomen Nerve dysfunction associated with injury to lower back, lumbar vertebrae and pelvis ”,“ neurological dysfunction associated with injury to shoulder and upper arm ”,“ neurological dysfunction associated with injury to elbow and forearm ”,“ wrist and hand injury ” Neurological dysfunction associated with hip and thigh injury, neurological dysfunction associated with knee and lower leg injury, neurological dysfunction associated with ankle and foot injury, multi-site Neurological dysfunction associated with injury, "Neurological dysfunction associated with trunk or limb damage," "Neurofunctional dysfunction that occurs as a secondary or sequelae of the effects of injury," "Other soft tissue disorders," "Inflammatory polyposis Joint disorders, " Nervous dysfunction associated with trauma during childbirth ”,“ Other disorders occurring during the perinatal period ”,“ Autonomic nervous system disorders ”,“ Neuromuscular junction diseases ”,“ Other paralytic syndromes ”,“ Muscular disorders ”,“ Systemic connective tissue disorder ”and the like.

In this specification, “neuropathy” refers to peripheral neuropathy such as neuritis and includes all of single (mono) neuropathy, multiple neuropathy, and complex neuropathies thereof. “Single (mono) neuropathy” includes upper arm single neuropathy (eg carpal tunnel syndrome, median neuropathy, ulnar neuropathy (eg, ulnar nerve palsy, delayed ulnar nerve palsy, etc.), radial neuropathy (eg, , Radial paralysis (Saturday night paralysis), radial canal syndrome, etc.), elbow canal syndrome, causalgia, etc., lower limb mononeuropathy (eg, sciatic nerve disorder, abnormal sensory femoral pain, femoral neuropathy, lateral knee) Foveal neuropathy, medial popliteal neuropathy, radial nerve palsy, compressive radial neuropathy, radial muscle atrophy, tarsal tunnel syndrome, plantar neuropathy, etc., and other single neuropathies (eg, intercostal neuropathy, multiple mononeuritis) , Diabetic mononeuropathy, local mononeuropathy, painful trauma mononeuropathy, etc.), and “multiple neuropathy” includes acute and Or chronic inflammatory neuropathy, hereditary and idiopathic neuropathy (eg, hereditary motility and sensory neuropathy, Charcot-Marie-Tooth disease, Dejelin-Sotta disease, hereditary pressure fragile neuropathy, refsum disease, hereditary movement Neuropathy associated with ataxia, idiopathic progressive neuropathy, hypertrophic interstitial neuropathy, sensorimotor neuropathy, motor sensory distal polyneuropathy, etc., inflammatory polyneuropathy (eg, acute inflammatory demyelinating polyneuropathy) Chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, laundry ascending paralysis, acute ascending motor neuropathy, serum neuropathy, vasculitis neuropathy, chronic relapsing polyneuropathy, etc., other polyneuropathy (eg, Multiple neuropathies due to stains (shingles, Lyme disease, leprosy, human immunodeficiency virus (HIV) infection, parasites (eg, mites) infection), multiple neuropathies due to neoplastic diseases such as cancer, multiple bone marrow Neuropathy due to tumor, polyneuropathy in monoclonal hypergammaglobulinemia, diabetic polyneuropathy, dyslipidemic neuropathy, neuropathy in sarcoidosis, neuropathy in amyloidosis, neuropathy in uremia, multiple occurrences in other endocrine and metabolic disorders neuropathy, polyneuropathy in acute intermittent porphyria, dystrophic neuropathy, vitamins (e.g., vitamin B _1, vitamin B _12, etc.) frequently in deficiency Nyuropa Qi, chronic pyridoxine toxic neuropathy, multiple neuropathies in systemic connective tissue disorders, multiple neuropathies in collagen vascular diseases (eg nodular polyarteritis, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis), other musculoskeletal disorders Polyneuropathy, drugs (eg, barbital, phenytoin, didanosine, sarcitabine, emetine, hexobarbital, chlorobutanol, sulfonamide, nitrofurantoin, triortocredyl phosphate, orthodinitrophenol, vinca alkaloids) Multiple neuropathies, painful trauma due to neuropathy, alcoholic polyneuropathy, other toxic substances (eg diphtheria toxin, heavy metals such as lead, dapsone, carbon monoxide, etc.) Originating neuropathy, and the like).

  In the present specification, examples of the “disorders of peripheral nerves other than neuropathy, cauda equina, nerve roots and plexus” include trigeminal nerve disorders (eg, idiopathic or symptomatic trigeminal neuralgia), glossopharyngeal nerve disorders (eg, , Idiopathic or symptomatic glossopharyngeal neuralgia), facial neuropathy (eg, unilateral facial palsy, clonic unilateral facial spasm, bell palsy, facial myokemia (myalgia), knee ganglionitis, Mercerson syndrome, atypical facial pain, etc.), other cranial nerve disorders (eg, olfactory neuropathy, vagus neuropathy, hypoglossal neuropathy, multiple cranial nerve disorders, multiple cranial nerve palsy in infections, multiple cranial nerve palsy in sarcoidosis , Multiple cranial nerve palsy in neoplastic diseases such as cancer, cranial nerve damage due to hematoma, etc.), painful tic, postherpetic neuralgia, neuralgic muscular atrophy, phantom limb syndrome, phantom limb pain, nerve Withdrawal injury, neurovascular syndrome, cervical radiculopathy, thoracic radiculopathy, lumbosacral radiculopathy, acute brachial neuritis, acute brachial plexitis, brachial plexus disorder, lumbosacral (bone) plexus disorder, Nervous dysfunction due to compression of nerve roots and plexus due to other diseases (eg painful nerve root disorders, multiple root disorders, thorax exit compression syndrome, scapulonervous nerve compression syndrome, anterior oblique muscle syndrome, neck Nerve dysfunction (eg, dorsal root ganglionitis due to cancer) due to compression of nerve roots and plexus due to neoplastic diseases such as rib syndrome, cancer (eg, metastatic cancer, breast cancer, lung cancer, neurofibroma, etc.), Nervous dysfunction due to compression of nerve root and plexus due to intervertebral disc disorder (hernia), nerve dysfunction due to compression of nerve root and plexus due to spinal disorder (eg, spondylosis, spinal canal stenosis, etc.), Mao God due to spinal canal stenosis Neurological dysfunction due to compression of nerve dysfunction due to compression of the nerve root and plexus by fibrosis, neurological function due to compression of the nerve root and plexus by hematoma failure, etc.).

  In the present specification, examples of the “disturbance of eye muscle, eye movement, accommodation and refraction” include, for example, cranial nerve palsy (for example, third cranial nerve (oculomotor nerve) paralysis, fourth cranial nerve (pulley nerve) paralysis, sixth cranial nerve ( Abduction nerve), paralysis, total (external) ocular muscle paralysis, progressive extraocular muscle paralysis, mitochondrial multisystem disease (eg ocular muscle paralysis, paralytic strabismus, etc.), oculomotor neuroneuropathy, abduction nerve mononeuropathy Other disorders of binocular movement (for example, joint gaze paralysis, internuclear (eye muscle) paralysis, convergence (spreading) failure, excessive vergence (spreading), etc.) and the like.

  In the present specification, examples of “neural dysfunction in inner ear disease” include vestibular dysfunction (eg, vestibular neuritis, Meniere's disease, benign seizure vertigo, etc.), other peripheral vertigo, central vertigo, etc. It is done.

  In the present specification, examples of the “viral infection characterized by skin and mucosal lesions” include herpes zoster (herpes zoster), rubella (germanial measles), Lyme disease, diphtheria and the like.

  In the present specification, examples of the “neurological dysfunction associated with protozoal diseases” include neurological dysfunction associated with chronic Chagas disease.

  In the present specification, “diabetes” includes insulin-dependent diabetes (IDDM), non-insulin-dependent diabetes (NIDDM) or diabetes associated with nutritional disorders, and “neuropathy in diabetes” includes, for example, Examples include diabetic neuritis, diabetic peripheral neuropathic pain, and painful upper lumbar neuropathy due to diabetes.

  In the present specification, “neurological dysfunction in metabolic disorders” includes, for example, sphingolipid metabolic disorders and lipid accumulation disorders (for example, nervous system ceroid lipofuscinosis, lipid storage disease, etc.), levum disease (phytane) Acid accumulation disease), amyloidosis (eg, neuropathic hereditary familial amyloidosis, etc.), neurological dysfunction in glycogenosis, neurodysfunction in mycosis, neurological dysfunction due to renal failure, neurological dysfunction due to adrenal disease, Examples include mitochondrial multisystem diseases (for example, ataxia, eye muscle paralysis, myopathy, etc.).

  In the present specification, examples of “neurological dysfunction in thyroid disorders” include neurological congenital iodine deficiency syndrome, hypothyroidism, and thyroid toxic myopathy.

  As used herein, “malignant neoplasm of mesothelial and soft tissue” includes, for example, the head, face, neck, upper limbs, lower limbs, thorax, abdomen, pelvis, peripheral nerves of the trunk and the autonomic nervous system or Examples include malignant neoplasms that develop at the boundary between the peripheral nerve and the autonomic nervous system.

  In the present specification, examples of “malignant neoplasms of cerebral nerves such as olfactory nerve, optic nerve, and auditory nerve” include optic glioma, acoustic nerve tumor (eg, vestibular Schwann cell tumor, bilateral acoustic nerve tumor, etc.), acoustic nerve pith And the like.

  In the present specification, examples of “neural dysfunction due to benign neoplasms of other parts of the cranial nerve, peripheral nerve and autonomic nervous system” include neurological dysfunction due to peripheral neurofibroma, Recklinghausen disease and the like.

  In the present specification, “head injury” includes, for example, cranial nerve damage (optic nerve and visual tract damage, oculomotor nerve damage, pulley nerve damage, trigeminal nerve damage, abduction nerve damage, facial nerve damage, acoustic nerve damage, accessory nerve damage, etc. Nerve damage, etc.).

  In the present specification, examples of “neurological dysfunction associated with cervical injury” include, for example, cerebral spinal cord shake and edema, dysfunction associated with cervical cord injury, cervical spinal nerve root injury, brachial plexus Injury, cervical peripheral nerve injury, cervical sympathetic nerve injury and the like.

  In the present specification, “neural dysfunction in spinal column (occipital atlas, cervical, cervico-thoracic, thoracic, thoracolumbar, lumbar, lumbosacral, sacral and sacroiliac) disorders” includes, for example, vertebral fractures , Spinal cord injury (contusion, laceration, disconnection, etc.), neurological dysfunction associated with acute transverse spinal cord injury, spinal disorder (eg, spondylosis, spinal stenosis, degenerative spinal disorder (degenerative spondylosis), degenerative joint , Neurological dysfunction in recurrent atlantoaxial joint dislocation with myelopathy (spinal cord disorder), spinal tuberculosis, neuropathic spinal disorder, etc., neurological dysfunction due to compression of cauda equina due to spinal canal stenosis, and other spinal disorders ( For example, intervertebral disc disorder, disc herniation (nuclear hernia), disc degeneration, disc rupture, disc prolapse, cervical spondylosis, cervical arm syndrome, spinal instability (symptom), back pain, neck pain, sciatica, sciatica Low back pain, lower back pain Thoracic pain, radiculopathy, spinal cord by hematoma disorders, progressive myelopathy, etc.) in neuronal dysfunction, spinal shock, Brown Sequard syndrome, and the like.

  In the present specification, examples of the “damage to the trunk and limbs” include, for example, “thorax damage”, “abdominal, lower back, lumbar and pelvic damage”, “shoulder and upper arm damage”, “elbow and forearm” Injury, wrist and hand injury, hip and thigh injury, knee and leg injury, ankle and foot injury and other trunk, limb nerves, spinal nerve roots and Examples include damage to the plexus.

  In the present specification, examples of “thoracic injury” include thoracic spinal cord shaking and edema, thoracic spinal cord injury, thoracic spinal nerve root injury, thoracic peripheral nerve injury, and thoracic sympathetic nerve injury. .

  In this specification, “damage of the abdomen, lower back, lumbar vertebra and pelvis” includes, for example, lumbar shaking and edema, lumbar injury, lumbar and sacral nerve root injury, cauda equina injury, lumbosacral Examples include plexus injury, sympathetic nerve damage in the lumbar region, sacrum and pelvis, peripheral nerve injury in the abdomen, lower back and pelvis.

  In the present specification, examples of the “shoulder and upper arm injury” include, for example, the ulnar nerve, median nerve, radial nerve injury, axillary nerve injury, muscle skin nerve injury, shoulder and upper arm skin sensory nerve injury, shoulder and upper arm. Multiple nerve injury and the like.

  In the present specification, examples of “injuries to the elbow and forearm” include ulnar nerve, median nerve, radial nerve damage of the forearm, skin sensory nerve damage of the forearm, multiple nerve damage of the forearm and the like.

  In the present specification, “wrist and hand injury” includes, for example, wrist and hand ulnar nerve, median nerve, radial nerve injury, finger nerve injury of the thumb, other finger nerve damage of the finger, wrist and hand. Examples include multiple nerve damage.

  In the present specification, examples of the “damage of the hip joint and the thigh” include, for example, hip joint and thigh sciatic nerve, femoral nerve damage, hip joint and thigh skin sensory nerve damage, hip joint and thigh multiple nerve damage, etc. Is mentioned.

  In the present specification, examples of “injuries of the knee and lower leg” include tibial nerve of the lower leg, peroneal nerve damage, skin sensory nerve damage of the lower leg, multiple nerve damage of the lower leg, and the like.

  In the present specification, the term “ankle and foot injury” includes, for example, lateral plantar nerve injury, medial plantar nerve injury, deep peroneal nerve injury of ankle and foot, skin sensory nerve injury of ankle and foot, ankle and foot Multiple nerve injury and the like.

  In the present specification, examples of “multi-site damage” include cervical nerve damage and cranial nerve damage accompanied by spinal cord damage.

  In this specification, “neural dysfunction occurring as a secondary / sequelae of the effects of damage” includes, for example, head injury (eg, superficial damage to the head, open wound of the head, skull and facial bone fractures, cranial nerves) Injury, eye and orbital damage, intracranial damage, etc.), neck and trunk damage (eg superficial damage to the neck and trunk and open wounds, vertebral fractures, other fractures of the rib cage and pelvis, spinal cord) Injury, intrathoracic organ damage, intraperitoneal and pelvic organ damage, etc.), upper limb damage (eg open upper limb wound, broken arm, wrist and hand fracture, upper limb dislocation, sprain and strain, upper limb nerve damage) , Upper limb muscle and tendon damage, upper limb crush injury and traumatic amputation, etc., lower limb damage (eg, lower limb open wounds, femoral fractures, other lower limb fractures, lower limb dislocation, sprains and strains, lower limbs) Nerve damage, lower limbs Damage of muscle and tendon, nerve dysfunctions such as occur as Sequelae of crush injury and traumatic amputation, etc.) of the lower limbs and the like.

  In the present specification, examples of the “soft tissue disorder” include rheumatoid arthritis (rheumatoid arthritis), myalgia, myalgia, neuralgia, neuritis, and extremity pain.

  In the present specification, examples of the “inflammatory multiple joint disorders” include neuropathic joint disorders.

  In this specification, “neurological dysfunction associated with trauma at birth (for example, damage to the peripheral nervous system such as cranial nerves (for example, facial nerves) during childbirth, damage due to traction during childbirth of the brachial plexus, etc.) Examples of "" include Elp palsy, Klumpke palsy, phrenic nerve palsy, etc. due to injury during childbirth.

  In the present specification, examples of the “disorder that occurred in the perinatal period” include, for example, neonatal myotonia disorder, transient neonatal myasthenia gravis, congenital hypertonia, Tomzen's disease, congenital hypotonia, neonate Other muscle tension disorders are listed.

  As used herein, “autonomic nervous system disorders” include, for example, idiopathic peripheral autonomic neuropathy, hereditary sensory autonomic neuropathy, familial autonomic dysfunction (Riley-Day syndrome), Horner syndrome, Examples include autonomic neuropathy in systemic degeneration, endocrine disease and metabolic disease, and myelopathy in other diseases.

  In the present specification, examples of the “disease of neuromuscular junction” include myasthenia gravis, neonatal myasthenia, congenital myasthenia syndrome, ocular myasthenia gravis, and other neuromuscular disorders (for example, Addictive (eg botulinum addiction) neuromuscular junction disease, toxic neuromuscular transmission disorders, endocrine disorders due to drugs or toxins (eg cholinergic drugs, antibiotics, organophosphate insecticides, nerve gases, etc.) Myasthenia Syndrome, Eaton-Lambert Syndrome, Systemic Ankylosia Syndrome, Isaac Syndrome, Myopathies, Intermittent Spasms, Pseudomuscular Stiffness, Myasthenia Syndrome in Neoplastic Diseases such as Cancer) and the like.

  In the present specification, the “paralytic syndrome” includes, for example, motor paralysis, paraplegia and limb paralysis (eg, relaxed paralysis, spastic paraplegia, flaccid limb paralysis, spastic limb paralysis, etc.), both upper limbs ( Side) Paralysis, upper limb monoplegia, lower limb monoplegia, other single palsy, lower limb spastic paralysis, cauda equina syndrome, bilateral quadriplegia, contralateral hemiplegia, alternation hemiplegia, etc.

  In the present specification, as the “muscular disease”, for example, muscular dystrophy (progressive muscular dystrophy, Duchenne muscular dystrophy, Becker muscular dystrophy, limb body muscular dystrophy, Emery-Drefus muscular dystrophy, which is a primary myopathy (myogenic disease), Distal muscular dystrophy (Miyoshi type and vacuolar type), facial scapula brachial (Landuzie dejerin) muscular dystrophy, myotonic (muscular tonic) muscular dystrophy, Steinert disease, ophthalopharyngeal muscular dystrophy, congenital muscular dystrophy, Fukuyama congenital Muscular dystrophy, merosin-positive congenital muscular dystrophy, merosin-negative congenital muscular dystrophy, etc.), dystrophin abnormalities, sarcoglycan abnormalities, Walker-Warburg syndrome, Santavoli syndrome, channelopati , Congenital myopathy, central core disease, centronuclear myopathy, nemarine myopathy, mitochondrial myopathy, infantile myopathy, inflammatory myopathy, other myopathy (eg, distal pharyngeal myopathy, empty distal myopathy, infection) (For example, trichinosis), myopathy in endocrine disease, myopathy due to hypothyroidism, thyroid toxic myopathy, myopathy in metabolic disease, myopathy in hypercalcemia, myopathy in hypophosphatemia, drug-induced Myopathy, alcoholic myopathy, myopathy caused by toxic substances, etc.), multiple systemic encephalomyopathy, progressive extraocular palsy, Kearns-Sayer syndrome, Melas syndrome, MERFF syndrome, mitochondrial encephalomyopathy, periodicity Limb paralysis Familial periodic paralysis, myoglobinuria, myositis (eg, interstitial myositis, traumatic ossification myositis, progressive ossification myositis, paralytic calcification and ossification of muscle, myositis in bacterial diseases, protozoa And myositis in parasitic infections, myositis in sarcoidosis, etc.), other myopathy (eg Cushing syndrome, acromegaly, immobility syndrome (paraplegia), muscle contracture, muscle wasting and atrophy, muscle strain, Myotonia, congenital myotonia, Tomsen's disease, congenital myotosis, etc.).

  In the present specification, examples of the “systemic connective tissue disorder” include dermatomyositis (for example, juvenile dermatomyositis, etc.), polymyositis, other systemic connective tissue diseases (for example, rheumatic polymyalgia, Skin (multiple myositis, etc.) in neoplastic diseases such as cancer.

  In this specification, the central nervous system diseases that cause motor dysfunction include “extrapyramidal disorders and abnormal movement”, “systematic atrophy”, “neurodegenerative disease”, “demyelinating disease”, “insertion”. Interstitial and seizure disorders "," cerebral palsy "," neurologic dysfunction due to other disorders of the central nervous system "," neural dysfunction due to inflammatory diseases of the central nervous system "," by viral infection of the central nervous system Neurological dysfunction ”,“ neuro dysfunction due to viral infections of the central nervous system characterized by skin and mucosal lesions ”,“ neuro dysfunction due to tuberculosis ”,“ neuro dysfunction due to infections that take sexual transmission ”, "Neural dysfunction that occurs as a secondary / sequelae of infection of the central nervous system", "Neural dysfunction due to protozoal diseases of the central nervous system", "Neural dysfunction due to helminthism of the central nervous system", "Neural function in nutritional deficiencies Disability " "Neuronal dysfunction due to malignant neoplasms of the brain and central nervous system or secondary malignant neoplasms", "Neurofunctional dysfunction due to benign neoplasms of the central nervous system", "Neural dysfunction associated with cerebrovascular disease", "Head Central nervous system neurological dysfunction associated with injury "," Central nervous system neurological dysfunction in spinal column disorders "," Neural dysfunction associated with pregnancy-related central nervous system maternal disorders "," Nerve dysfunction associated with delivery / partum " Dysfunction ”,“ neurological dysfunction of the central nervous system due to trauma during childbirth ”,“ neurological dysfunction due to perinatal disorders ”,“ addiction and / or subsequent use of drugs, drugs and biologics ” "Neuronal dysfunction caused by sequelae", "Toxic action of non medicinal substances (addiction) and / or its subsequent / neurological disorder", "Other action and / or its secondary Neurological dysfunction "and the like caused by the after-effects and the like.

  In the present specification, examples of “extrapyramidal disorder and abnormal movement” include, for example, Parkinson's disease, primary Parkinson's syndrome, secondary Parkinson's syndrome, juvenile Parkinson's syndrome, malignant syndrome, neuroleptic malignant syndrome, drug-induced Secondary Parkinsonism, post-encephalitic Parkinsonism, degenerative diseases of the basal ganglia (eg Hallerfolden-Spatz disease, progressive supranuclear (eye muscle) paralysis (Steel Richardson Orzewsky disease), striatal nigra Degeneration), dyskinesia (abnormal movement), dystonia (dystonia) (eg drug-induced dystonia, idiopathic familial dystonia, idiopathic non-familial dystonia, systemic dystonia (degenerative muscular dystonia), local dystonia , Spastic torticollis, idiopathic orofacial dystonia, blepharospasm, medullary dystonia, etc.), other Extracorporeal dysfunction and abnormal movement (eg tremor (eg essential tremor, drug-induced tremor, stationary tremor in Parkinson's disease, tremor in cerebellar disease, hepatic flapping tremor (difficulty in holding a fixed posture) , Intentional tremors, etc.), myoclonus (eg, palatal myoclonus, progressive myoclonic epilepsy, operational myoclonus, myoclonus after head trauma or hypoxic-ischemic brain injury, Alzheimer's myoclonus, late viral infection (eg, Creutzfeldt-Jakob disease, subacute sclerosing panencephalitis, etc.) Myoclonus, Myoclonus in uremia etc.), Drug-induced chorea, Chronic progressive chorea, Hereditary chorea, Other chorea-Ataxia (Eg Sydenham chorea, pregnancy chorea), tic (eg drug-induced tic, organic cause) According ticks, etc.), hereditary multiple tic disorder (Tourette's syndrome), athetosis, chorea athetosis exercise, Hemiparizumu, periodic limb movement disorder, restless legs syndrome, etc.).

  In this specification, “systematic atrophy” includes, for example, Huntington's disease (Huntington's chorea), hereditary ataxia (eg, congenital non-progressive ataxia, premature cerebellar ataxia, evening Onset cerebellar ataxia, cerebellar ataxia with impaired DNA repair, hereditary spastic paraplegia, familial spastic paraplegia, etc., spinal (progressive) muscular atrophy and related syndromes (eg, type 1) Infant spinal muscular atrophy (Welndig-Hoffmann's disease), Waldhard Kugelberg-Wehlander disease, bulbar spinal muscular atrophy (Kennedy Alter-Sun syndrome), other hereditary spinal muscular atrophy Progressive neuromuscular atrophy, other motor neuron diseases (motor neuropathy, corticospinal tract, anterior horn cells and / or medullary motor nucleus disorders and other diseases associated therewith), primary lateral sclerosis, Amyotrophic lateral sclerosis (Lou Gehrig's disease), familial amyotrophic lateral sclerosis, progressive bulbar paralysis, progressive pseudospherical paralysis, neoplasm-related neuromyopathy and neuropathies (eg, neoplasm (tumor)) Associated syndromes, systemic atrophy that impairs the central nervous system in neoplastic diseases, systemic atrophy that impairs the central nervous system in myxedema, etc.).

  In the present specification, examples of the “neurodegenerative disease” include Alzheimer's disease (early / late), focal cerebral atrophy, senile brain degeneration, nervous system degeneration due to alcohol, and diffuse Lewy bodies. Disease, cerebral cortex basal ganglia degeneration, spinocerebellar degeneration, Friedreich ataxia, cerebellar ataxia, multisystem atrophy, olive bridge cerebellar atrophy, Maccard Joseph disease (Zolea type motor system degeneration), shy Dräger syndrome (cerebellar ataxia), late-onset cerebellar cortical atrophy, familial spinocerebellar ataxia, dentate nucleus erythronuclear pallidus louis atrophy, Tay-Sachs disease (hexosaminidase A deficiency) ), Subacute associated spinal degeneration.

  In the present specification, examples of “demyelinating diseases” include multiple sclerosis, acute disseminated demyelinating diseases (for example, optic neuromyelitis (Devik's disease), acute and subacute hemorrhagic leukoencephalitis (Hurst), etc. ), Diffuse (diffusion) sclerosis, central demyelination of the corpus callosum, central pontine myelination, general sclerosis, acute disseminated encephalomyelitis, acute encephalitis, transverse myelitis, demyelinating Examples include acute transverse myelitis, subacute necrotizing myelitis, concentric sclerosis (Barrow), and leukodystrophy (for example, adrenoleukodystrophy) in the disease.

  In the present specification, examples of the “interstitial and seizure disorder” include migraine (ordinary migraine without aura, classic migraine with aura), migraine persistent state Headache syndrome (eg cluster headache syndrome, vascular headache, tension headache, chronic posttraumatic headache, drug-induced headache, etc.), transient cerebral ischemic attack and related syndromes (eg vertebral basilar artery syndrome, neck Neurological dysfunction associated with arterial syndrome (hemispheric), multiple and bilateral brain (parenchymal) external artery syndrome, transient cataract, etc., cerebral vascular syndrome in cerebrovascular disease (eg middle cerebral artery syndrome) , Anterior cerebral artery syndrome, posterior cerebral artery syndrome, brain stem stroke syndrome, cerebellar stroke syndrome, pure motor multiple small infarction (Rakune) syndrome, pure sensory multiple small infarction (Rakne) syndrome, etc.) Can be mentioned.

  In the present specification, as “cerebral palsy”, for example, spastic cerebral palsy, spastic bilateral (side) palsy, pediatric hemiplegia, dyskinesia cerebral palsy, ataxic cerebral palsy, hemiplegia (for example, relaxed hemiplegia, Spastic hemiplegia, etc.).

  In the present specification, “other disorders of the central nervous system” refers to other disorders of the brain (for example, hydrocephalus (eg, hydrocephalus, obstructive hydrocephalus, normal pressure hydrocephalus, posttraumatic hydrocephalus, Hydrocephalus in infectious diseases, hydrocephalus in neoplastic diseases such as cancer), toxic encephalopathy, brain cysts, anoxic brain injury, benign intracranial hypertension, fatigue syndrome after viral infection, encephalopathy (encephalopathy) , Cerebral compression, cerebral edema, Reye syndrome, etc.), other spinal disorders (eg, syringomyelia, medullary cavernosis, vascular myelopathy, spinal cord compression, acute spinal cord compression, subacute spinal cord compression, chronic spinal cord compression), Cerebrospinal fluid leakage, meningopathies, post-treatment disorders of the nervous system (eg cerebrospinal fluid leakage from spinal tap, response to spinal and lumbar puncture, hypocranial pressure secondary to ventricular shunt (low brain pressure) Etc.), Proteus syndrome, etc. .

  In the present specification, the “inflammatory disease of the central nervous system” includes, for example, meningitis in infectious diseases (for example, bacterial meningitis (for example, H. influenzae meningitis, pneumococcal meningitis, Streptococcal meningitis, staphylococcal meningitis, etc.), meningitis in viral diseases, meningitis in mycosis, etc.), other meningitis (eg non-suppurative meningitis, chronic meningitis) Inflammation, benign recurrent meningitis (morale meningitis, etc.), encephalitis, myelitis and encephalomyelitis (eg, acute disseminated encephalitis, tropical spastic paraplegia, bacterial meningoencephalitis) And meningomyelitis, encephalitis, myelitis and encephalomyelitis etc. in infectious diseases (eg bacterial diseases, viral diseases etc.), intracranial (eg epidural and subdural) abscesses and granulomas, spine Intraductal abscess and granulomas, intracranial and intravertebral phlebitis and thrombus (sex) Flame, and the like.

  In the present specification, examples of the “viral infection of the central nervous system” include, for example, paralytic or non-paralytic acute gray leukitis (polio), slow viral infection (for example, Creutzfeldt-Jakob disease, subacute sclerosis) Encephalitis (SSPE), progressive multifocal leukoencephalopathy, etc.), enteric viral rash (Boston rash), epidemic dizziness, coxsackie virus infection, enterovirus infection, and the like.

  In the present specification, examples of the “viral infection of the central nervous system characterized by skin and mucosal lesions” include, for example, herpes zoster (herpes zoster), herpes zoster encephalitis, herpes zoster meningitis, rubella (German measles) ) And the like.

  In the present specification, examples of “neurological dysfunction due to tuberculosis” include neurological dysfunction due to tuberculous meningitis, meningeal (sex) tuberculoma, and the like.

  In the present specification, “infectious diseases having a sexual transmission mode” include, for example, congenital syphilis (eg, late congenital neurosyphilis (juvenile neurosyphilis), etc.), late syphilis, overt neurosyphilis, asymptomatic nerves Examples include syphilis and neurosyphilis.

  In this specification, “neural dysfunction that occurs as a secondary / sequelae of central nervous system infection (eg, central nervous system tuberculosis, gray leukitis (polio), leprosy, AIDS, viral encephalitis, etc.)” , Post-polio syndrome, post-polio muscle atrophy, neuritis in leprosy, neuritis in AIDS, and the like.

  In the present specification, examples of the “protozoal diseases of the central nervous system” include falciparum malaria accompanied by cerebral complications, chronic Chagas disease and the like.

  In the present specification, examples of the “central nervous system helminthiasis” include central nervous system scab (tail) worms.

In this specification, “neurological dysfunction in nutritional deficiencies (eg, thiamine deficiency, vitamin B ₁ deficiency, vitamin B ₁₂ deficiency, etc.)” includes, for example, Wernicke encephalopathy (encephalopathy), abetalipoproteinemia ( Bassen-Kornz Bike Syndrome).

  In the present specification, examples of the “malignant neoplasm of the brain and central nervous system” include, for example, the brain (cerebrum, frontal lobe, temporal lobe, parietal lobe, excluding the brain lobe and ventricle, occipital lobe, ventricle, cerebellum, brain stem. , Brain border lesions), meninges (brain meninges, spinal cord membranes), spinal cord, cauda equina, malignant neoplasms that develop at the borders of other parts of the central nervous system (eg brain tumors (eg astrocytomas) And brain abscess))) and the like.

  In the present specification, the “benign neoplasm of the central nervous system” includes, for example, central neurofibroma, epidural abscess, subdural abscess, epidural tumor, meningioma (brain meningioma, spinal cord marrow) And so on).

  In the present specification, examples of the “cerebrovascular disease” include stroke, cerebral hemorrhage (eg, hypertensive intracerebral hemorrhage, subarachnoid hemorrhage, subdural hemorrhage, epidural hemorrhage, etc.), cerebral infarction (eg, cerebral thrombosis, Cerebral embolism, etc.), transient cerebral ischemic attack, reperfusion injury, extracerebral artery occlusion and stenosis, cerebral artery occlusion and stenosis, non- (un) ruptured dissection of cerebral artery wall, non (un) rupture Cerebral aneurysm, cerebral artery atherosclerosis (disease), progressive vascular leukoencephalopathy, hypertensive encephalopathy, moyamoya disease (Willis arterial occlusion), non-suppurative thrombosis of intracranial venous system, Examples include cerebral arteritis, cerebral amyloid angiopathy, cerebral arteritis in infectious diseases, and blood volume reducing shock.

  In the present specification, as "head injury of the central nervous system", for example, intracranial injury, shaking, traumatic brain edema, diffuse brain injury, localized brain injury, epidural hemorrhage, traumatic dura mater Examples include subhemorrhage, traumatic subarachnoid hemorrhage, cerebral contusion, penetration, shear, compression, laceration, labor trauma, infant whiplash swaying syndrome, and the like.

  In the present specification, as "the nerve dysfunction of the central nervous system in the spinal column (occipital atlas, cervical, cervico-thoracic, thoracic, thoracolumbar, lumbar, lumbosacral, sacral and sacroiliac)" For example, spinal fracture, spinal cord injury (contusion, laceration, amputation, etc.), neurological dysfunction associated with acute transverse spinal cord injury, spinal disorder (eg, spondylosis, spinal canal stenosis, degenerative spinal disorder (degenerative spondylosis)) , Osteoarthritis, recurrent atlantoaxial joint subluxation with myelopathy, spinal tuberculosis, neuropathic spinal disorder, etc.), nerve dysfunction due to compression of cauda equina due to spinal canal stenosis, etc. Spinal disorders (for example, intervertebral disc disorders, intervertebral disc herniation, intervertebral disc degeneration, intervertebral disc rupture, intervertebral disc prolapse, cervical spondylosis, cervical arm syndrome, spinal instability, back pain, cervical pain, sciatica, sciatica Low back pain, Back pain, thoracic pain, radiculopathy, spinal cord due to hematoma disorder, progressive spinal cord disorder, etc.) in neuronal dysfunction, spinal shock, Brown-Sequard syndrome, and the like.

  In this specification, “maternal disorders of the central nervous system related to pregnancy (eg, anesthetic complications during pregnancy (eg, central nervous system complications due to anesthesia, toxic response to local anesthesia, spinal cord or epidural anesthesia induced) Examples of the “neurologic dysfunction associated with headache etc.)” include chorea of pregnancy.

  In this specification, “neurological dysfunction associated with parturition / partum” includes, for example, anesthesia complications in parturition / partum (eg, central nervous system complications of anesthesia, poisoning response to local anesthesia, spinal anesthesia and epidural Neurological dysfunction associated with anesthesia-induced headache and the like).

  In the present specification, “traumatic injury at the time of delivery of the central nervous system” includes, for example, damage at the time of delivery of the central nervous system (for example, brain edema due to damage at delivery, brain injury due to damage at delivery, spine and spinal cord) Damage at the time of childbirth).

  In the present specification, “disorders occurring in the perinatal period” include, for example, neonatal brain abnormalities (for example, neonatal cerebral ischemia, neonatal acquired periventricular cyst, neonatal brain white matter softening, neonatal brain Irritability, neonatal brain suppression, neonatal coma, etc.).

  As used herein, “drugs, drugs and biological products that cause neurological dysfunction due to intoxication and / or its subsequent / sequelae” include, for example, systemic antibiotics, systemic antiinfectives, antiparasitic drugs, hormones , Synthetic alternatives and antagonists, non-opioid analgesics, antipyretic drugs, anti-rheumatic drugs, narcotics, psychopathic drugs (halogens), anesthetics, therapeutic gases, antiepileptic drugs, sedative / hypnotics Anti-parkinsonian drugs, psychotropic drugs, drugs acting mainly on the autonomic nervous system, drugs acting mainly on the whole body and blood, drugs acting mainly on the cardiovascular system, drugs acting mainly on the digestive system, mainly smooth muscle, Drugs that affect skeletal muscle and respiratory system, topical drugs that mainly affect the skin and mucous membranes, ophthalmic drugs, otolaryngology and dental drugs, diuretics, other drugs, drugs and Biologicals, and the like.

  In the present specification, “substances that are not mainly medicinal substances that cause neurological dysfunction due to toxic effects (addiction) and / or their subsequent / sequelae” include, for example, alcohols, organic solvents, aliphatic and aromatic hydrocarbon halogens Derivatives, corrosive substances, soaps, detergents, metals (lead, organic mercury, etc.), other inorganic substances (arsenic, cadmium, etc.), carbon monoxide, other gases (sarin, soman, tabun, VX gas, etc.), Examples include fumes and steam, agricultural chemicals, harmful substances ingested as marine foods, other harmful substances ingested as food, contact with toxic animals, food contaminants due to aflatoxins and other fungal toxins (such as mycotoxins), and the like.

  In the present specification, examples of the “other effects that cause neurological dysfunction” include thermal syncope, thermal (sexual) convulsions, ear pressure trauma, and the like caused by radiation, heat, light, atmospheric pressure, or water pressure. Examples include sinus pressure trauma, latent disease (decompression disease), angioedema and / or its secondary / sequelasis.

  In the present specification, other symptoms and signs considered to be motor dysfunction include the following “numbness, pain and neuropathic pain”, “symptoms and signs related to the nervous system and musculoskeletal system”, “skin and Symptoms and Signs Related to the Subcutaneous Tissue, Symptoms and Signs Related to Conversation and Speech, Symptoms and Signs Related to Cognition, Perception, Emotional State, and Behavior, “Behavioral and Emotional Disorders Developing in Childhood, Childhood, and Adolescence Examples of “numbness, pain and neuropathic pain” include numbness, acute pain, acute postoperative pain, postoperative pain syndrome (eg, postmastectomy syndrome, stump pain, etc.), chronic Pain, chronic intractable pain (allodynia), peripheral neuropathic pain, cancer pain, neuropathic pain syndrome, painful traumatic mononeuropathy, painful polyneuropathy Examples include diabetic peripheral neuropathic pain, central pain syndrome, complex local pain syndrome, reflex sympathetic dystrophy, burning pain, phantom limb pain, causalgia, Ramsey Hunt syndrome, etc. "For example, abnormal involuntary movement (dyskinesia) (for example, abnormal head movement, tremor, (painful) convulsions, muscle fiber bundle spasm, periodic limb movement disorder, restless leg syndrome, etc.), walking And movement abnormalities (eg, ataxic gait, paralytic gait, difficulty walking), other coordination disorders (eg, ataxia, cerebellar ataxia (Shy-Drager syndrome), telangiectasia ataxia) Etc.), other symptoms and signs related to the nervous system and musculoskeletal system (eg, tetany, meningopathy, abnormal reflexes, abnormal extensor reflexes of the sole) Babinsky signs, abnormal posture, hip joint click, spasticity, hypertonia, myotonia, deep tendon reflexes, hypotonia, myalgia, dysphagia, gaze crisis, etc.) Examples of the symptoms and signs related to skin sensory disorders (for example, loss of perception of the skin (sensory), reduction, abnormalities (symptoms), glove-type sensory impairment, tinel symptoms (interference), hypersensitivity (sensory), tactile sensation Hypersensitivity, hyperalgesia, etc.), and “speech and voice-related symptoms and signs” include, for example, speech disorders (eg, aphasia, aphasia, dysarthria, ataxia, etc.), voice disorders (eg, Dysphonia (difficult to speak), loss of speech (impossible to speak), high and low nasal sounds, etc., speech and language specific developmental disorders (eg, specific speech dysarthria, expressive language disorder, receptive language disorder) , Acquired aphasia with epilepsy (Landau-Krefner syndrome), etc.), etc., as "cognition, perception, emotional state and behavioral symptoms and signs", for example, dizziness, staggering, olfactory disturbance (for example, No olfactory sensation, olfactory illusion (eg, olfactory sensation)), taste disorders (eg, gustatory illusion (inclusion)), other symptoms and signs related to general sensation and perception (eg, hallucinations, hallucinations, other hallucinations, etc.) ), Specific developmental disorders of motor function, etc., and “behavioral and emotional disorders that develop in childhood, childhood and adolescence” include, for example, tic disorders (eg, transient tic disorders, chronic exercise) Usually occurring in childhood (childhood) and adolescence, including sexual or vocal tic disorders, tic disorders including both voice and polymotility (Jill de la Tourette syndrome), etc. Behavioral and emotional disorders (e.g., stereotypic movement disorder, stuttering, twisters (randomness) Language diseases etc.) and the like.

  In the present specification, the term “neural dysfunction” includes all neurological dysfunctions.

  In the present specification, “treatment” means that the disease state is guided in the direction of healing, and “progression inhibition” means that the progression of the symptom is suppressed and the progression of the disease state is stopped.

  In the present invention, (2R) -2-propyloctanoic acid is a compound represented by the formula (A)

(Where

Represents the β-configuration. )
It is a compound shown by these.

  The salt of (2R) -2-propyloctanoic acid is preferably a water-soluble salt having low toxicity. For example, a salt of an alkali metal (potassium, sodium, lithium, etc.), an alkaline earth metal (calcium, magnesium, etc.) Salts, ammonium salts (eg, tetramethylammonium salt, tetrabutylammonium salt, etc.), organic amines (eg, methylamine, dimethylamine, trimethylamine, triethylamine, monoethanolamine, diethanolamine, triethanolamine, cyclopentylamine, benzylamine) , Phenethylamine, dicyclohexylamine, dibenzylamine, N, N′-dibenzylethylenediamine, tris (hydroxymethyl) methylamine, N-methyl-D-glucamine, pyridine, picoline, piperidine, etc. Salts of basic amino acids (such as arginine, lysine, ornithine, histidine, etc.) and the like salts with the. Among these salts, more preferred are, for example, alkali metal salts or salts with basic amino acids, and sodium salts are particularly preferred.

  As a solvate of (2R) -2-propyloctanoic acid or a salt thereof, a water-soluble one having low toxicity is preferable. For example, solvates such as water and alcohol solvents (for example, methanol, ethanol, etc.) Is mentioned.

  In the present invention, (2R) -2-propyloctanoic acid, a salt thereof, or a solvate thereof is not limited to a substance that is substantially pure and is a single substance, but includes impurities (for example, byproducts derived from the production process. Products, solvents, raw materials or decomposed products, etc.) may be contained as long as they are acceptable as a drug substance. The content of impurities acceptable as an active pharmaceutical ingredient varies depending on the impurities contained therein. For example, heavy metals are about 20 ppm or less, optical isomers are about 5 mass% or less, 2-propanol or heptane which is a residual solvent is The total is preferably about 5000 ppm or less, and the water content is preferably about 0.2 mass% or less. The optical purity of (2R) -2-propyloctanoic acid used in the present invention is preferably 99% ee or more, and more preferably 99.3% ee or more.

  In the present invention, the prodrug of (2R) -2-propyloctanoic acid is a derivative of (2R) -2-propyloctanoic acid, as used by those skilled in the art, and is enzymatic or chemical in the body. Any compound can be used as long as it is converted to (2R) -2-propyloctanoic acid, and its structure is not particularly limited. Examples of the prodrug of (2R) -2-propyloctanoic acid include compounds in which a carboxy group is esterified (for example, methyl ester, ethyl ester, phenyl ester, carboxymethyl ester of (2R) -2-propyloctanoic acid , Dimethylaminomethyl ester, pivaloyloxymethyl ester, ethoxycarbonyloxyethyl ester, phthalidyl ester, (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl ester, or cyclohexyloxycarbonylethyl Esters, etc.), compounds in which the carboxy group is amidated (for example, methylamide, ethylamide, or phenylamide of (2R) -2-propyloctanoic acid), compounds in which the carboxy group is reduced, and protected forms thereof (for example, ( 2R 2-propyl octanol or acetic acid (2R) -2-propyl octanyl ester) and the like, can be mentioned. These compounds can be produced by known methods. In addition, the prodrug of (2R) -2-propyloctanoic acid is (2R) under physiological conditions as described in Yodogawa Shoten 1990, “Drug Development”, Volume 7 “Molecular Design”, pages 163-198. ) It may be changed to 2-propyloctanoic acid. Further, the prodrug of (2R) -2-propyloctanoic acid may be a salt or a solvate. The salt of the prodrug is preferably a non-toxic and water-soluble salt, such as an alkali metal (potassium, sodium, lithium, etc.) salt, an alkaline earth metal (calcium, magnesium etc.) salt, an ammonium salt ( For example, tetramethylammonium salt, tetrabutylammonium salt, etc.), organic amine (eg, methylamine, dimethylamine, trimethylamine, triethylamine, monoethanolamine, diethanolamine, triethanolamine, cyclopentylamine, benzylamine, phenethylamine, dicyclohexylamine, Salts with dibenzylamine, N, N′-dibenzylethylenediamine, tris (hydroxymethyl) methylamine, N-methyl-D-glucamine, pyridine, picoline, piperidine, etc.) Salts with acid (eg, arginine, lysine, ornithine, histidine, etc.), acid adduct salts (eg, inorganic acids (eg, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid, nitric acid, etc.)) Salts and organic acids such as acetic acid, trifluoroacetic acid, lactic acid, tartaric acid, oxalic acid, fumaric acid, maleic acid, benzoic acid, citric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, Salt) with isethionic acid, glucuronic acid, gluconic acid and the like.

  In the present specification, “(2R) -2-propyloctanoic acid, salt, solvate or prodrug thereof” includes (2R) -2-propyloctanoic acid, (2R) -2-propyloctane. Sodium salt of acid, phenethylamine salt of (2R) -2-propyloctanoic acid, (2R) -2-propyloctanoic acid methyl ester and the like are preferable, and (2R) -2-propyloctanoic acid is more preferable.

  (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof, or a prodrug thereof may be obtained by a method known per se, for example, European Patent No. 0632008, WO99 / 58513, International It can be produced according to the methods described in JP-A-00 / 48982, pamphlet No. 3032447, patent No. 3084345, etc., or by appropriately combining these methods. Moreover, you may attach | subject to processes, such as freeze-drying, as desired.

In the present invention, all isomers are included unless otherwise specified. For example, isomers (R, S form, α, β configuration, enantiomers, diastereomers), optically active substances having optical activity (D, L, d, l forms), chromatographic separation due to the presence of asymmetric carbon, etc. Polar bodies (high polar bodies, low polar bodies), mixtures of these in arbitrary proportions, and racemic mixtures are all included in the present invention. In addition, (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof, or a prodrug thereof may be labeled with an isotope (for example, ³ H, ¹⁴ C, ³⁵ S, ¹²⁵ I, etc.).

[Application to pharmaceutical products]
A drug containing the (2R) -2-propyloctanoic acid, salt, solvate or prodrug thereof of the present invention (hereinafter sometimes abbreviated as “drug of the present invention”). It is useful as a preventive, therapeutic and / or progress inhibitor for motor dysfunction. The motor dysfunction includes all of “motor dysfunction caused by peripheral nervous system disease”, “motor dysfunction caused by central nervous system disease”, and “symptoms and signs of other motor dysfunctions not classified as such”. Include. Peripheral nervous system diseases that cause motor dysfunction include, for example, neuropathy (mono) neuropathy (upper leg single neuropathy (eg carpal tunnel syndrome, median neuropathy, ulnar neuropathy (eg, ulnar nerve palsy, Delayed ulnar nerve paralysis, etc.), radial nerve disorders (eg, radial nerve paralysis (Saturday night paralysis), radial canal syndrome, etc.), elbow canal syndrome, causalgia, etc.) lower limb mononeuropathy (eg, sciatic nerve) Disorder, abnormal sensory femoral pain, femoral neuropathy, lateral popliteal neuropathy, medial popliteal neuropathy, radial nerve palsy, compressive radial neuropathy, radial muscle atrophy, tarsal tunnel syndrome, plantar neuropathy, etc.) Single neuropathy (eg, intercostal neuropathy, polyneuropathy, diabetic mononeuropathy, local mononeuropathy, painful trauma mononeuropathy Etc.), polyneuropathy (hereditary and idiopathic neuropathy (eg, acute and / or chronic inflammatory neuropathy, hereditary motility and sensory neuropathy, Charcot-Marie-Tooth disease, DeJerlin-Sota disease, hereditary pressure vulnerability) Neuropathy, refsum disease, neuropathy associated with hereditary ataxia, idiopathic progressive neuropathy, hypertrophic interstitial neuropathy, sensorimotor neuropathy, motor sensory distal multiple neuropathy, etc.), inflammatory multiple neuropathy ( For example, acute inflammatory demyelinating polyneuropathy, chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, laundry ascending paralysis, acute ascending motor neuropathy, serum neuropathy, neuropathy due to vasculitis, chronic relapsing polyneuropathy, etc. , Other polyneuropathy (eg, polyneuropathy due to infection (such as herpes zoster, Lyme disease, leprosy, human immunodeficiency virus (HIV) infection, parasite (eg, tick) infection), etc.) Multiple neuropathies due to disease, neuropathies due to multiple myeloma, multiple neuropathies in monoclonal hypergammaglobulinemia, diabetic polyneuropathy, dyslipidemic neuropathy, neuropathy in sarcoidosis, neuropathy in amyloidosis, neuropathy in uremia, etc. Multiple neuropathies in endocrine and metabolic diseases, multiple neuropathies in acute intermittent porphyria, dystrophic neuropathy, vitamins (eg, vitamin B) ₁ , Vitamin B ₁₂ Etc.) Multiple neuropathies in deficiency, Chronic pyridoxine toxic neuropathy, Multiple neuropathies in systemic connective tissue disorders, Collagen vascular disease (eg nodular polyarteritis, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, etc.), etc. Neuropathy, drugs (eg, barbital, phenytoin, didanosine, sarcitabine, emetine, hexobarbital, chlorobutanol, sulfonamide, nitrofurantoin, triortocresyl phosphate, orthodinitrophenol, vinca alkaloids Etc.) Induced polyneuropathy, alcoholic polyneuropathy, other toxic substances (eg diphtheria toxin, heavy metals such as lead, dapsone, carbon monoxide, etc.) Polyneuropathy, painful traumatic polyneuropathy, etc.)), nerves other than neuropathy, cauda equina, nerve roots and plexus disorders (eg trigeminal neuropathy (eg idiopathic or symptomatic trigeminal neuralgia, etc.), glossopharynx Neuropathy (eg, idiopathic or symptomatic glossopharyngeal neuralgia), facial neuropathy (eg, unilateral facial palsy, clonic unilateral facial spasm, bell palsy, facial myokiemia (myalgia), knee-like Ganglionitis, Mercerson syndrome, atypical facial pain, etc.), other cranial nerve disorders (eg, olfactory neuropathy, vagus neuropathy, hypoglossal neuropathy, polyencephalopathy, multiple cranial nerve palsy in infections, sarcoidosis) Multiple cranial nerve palsy, multiple cranial nerve palsy in neoplastic diseases such as cancer, cranial nerve damage due to hematoma, etc.), painful tics, postherpetic neuralgia, neuralgic muscles Atrophy, phantom limb syndrome, phantom limb pain, nerve root extraction injury, neurovascular syndrome, cervical radiculopathy, thoracic spinal radiculopathy, lumbosacral radiculopathy, acute brachial neuritis, acute brachial plexitis, upper arm Nervous dysfunction due to nerve plexus disorders, lumbosacral (bone) plexus disorders, nerve root and plexus compression due to other diseases (eg, painful nerve root disorders, multiple root disorders, chest outlet compression syndrome, scapula) Nerve function due to nerve root and plexus compression due to neurovascular compression syndrome, anterior oblique muscle syndrome, cervical rib syndrome, cancer and other neoplastic diseases (eg metastatic cancer, breast cancer, lung cancer, neurofibroma, etc.) Nerve roots and plexus due to disorders (eg, dorsal root ganglionitis due to cancer), nerve dysfunction due to compression of nerve roots and plexus due to disc damage (hernia), spinal disorders (eg spondylosis, spinal canal stenosis, etc.) Nervous machine caused by compression Dysfunction, nerve dysfunction due to compression of cauda equina due to spinal canal stenosis, nerve dysfunction due to nerve root and plexus compression due to fibrosis, nerve dysfunction due to compression of nerve root and plexus due to hematoma), eye muscle, Impairment of eye movement, accommodation and refraction (eg cranial nerve palsy (eg third cranial nerve (oculomotor nerve) paralysis, fourth cranial nerve (pulley nerve) paralysis, sixth cranial nerve (abduction nerve) paralysis, total (external) ocular muscle) Paralysis, progressive extraocular palsy, mitochondrial multisystem disease (eg, ocular palsy), paralytic strabismus, etc., oculomotor mononeuropathy, abductor mononeuropathy, other disorders of binocular movement (eg, joint Neurological dysfunction in inner ear diseases (eg vestibular dysfunction (eg vestibular neuritis, menie)) Disease, benign paroxysmal vertigo, etc.), other peripheral vertigo, central vertigo, etc.), viral infections characterized by skin and mucosal lesions (eg, herpes zoster (herpes zoster), rubella (German measles), Lyme disease , Diphtheria, etc.), neurological dysfunction associated with protozoan diseases (eg, chronic Chagas disease, etc.), diabetes (insulin dependent diabetes mellitus (IDDM), non-insulin dependent diabetes mellitus (NIDDM) or nutritional disorders (Eg, diabetic neuritis, diabetic peripheral neuropathic pain, painful upper lumbar neuropathy due to diabetes, etc.), neurological dysfunction in metabolic disorders (eg, sphingolipid metabolic disorders and lipid accumulation disorders ( For example, neurological dysfunction in nervous system ceroid lipofuscinosis, lipid storage disease, etc., Lefsum disease (phyta Acid accumulation disease), amyloidosis (eg, neuropathic hereditary familial amyloidosis, etc.), neurological dysfunction in glycogenosis, neurodysfunction in mycosis, neurological dysfunction due to renal failure, neurological dysfunction due to adrenal disease, Mitochondrial multisystem disease (eg, ataxia, ocular palsy, myopathy, etc.), neurological dysfunction in thyroid disorders (eg, congenital iodine deficiency syndrome, hypothyroidism, thyroid toxic myopathy, etc.), moderate Neural dysfunction due to malignant neoplasms of skin and soft tissue (eg, head, face, neck, upper limb, lower limb, thorax, abdomen, pelvis, trunk peripheral nerve and autonomic nervous system or peripheral and autonomic nervous system Neurological dysfunction due to malignant neoplasms at the border with the other), malignant neoplasms of other cranial nerves (eg olfactory nerve, optic nerve, auditory nerve, etc.) Neurologic dysfunction due to optic glioma, acoustic nerve tumor (eg vestibular schwannoma, bilateral acoustic nerve tumor, etc.), acoustic neuromyeloma, etc., due to benign neoplasms of other parts of the cranial nerve, peripheral nerve and autonomic nervous system Neurological dysfunction (eg, neurological dysfunction due to peripheral neurofibroma, Recklinghausen's disease, etc.), head injury (eg, cranial nerve damage (optic nerve and visual tract damage, oculomotor nerve damage, pulley nerve damage, trigeminal nerve damage, Neurological dysfunction associated with abductor nerve injury, facial nerve injury, acoustic nerve injury, accessory nerve injury, etc.), neurological dysfunction associated with cervical injury (for example, cervical shake and edema neurological dysfunction, cervical spinal cord injury) Nervous dysfunction associated with injury, cervical vertebral root injury, brachial plexus damage, cervical peripheral nerve injury, cervical sympathetic nerve injury, etc.), spinal column (occipital ring axis, cervical, cervical chest, chest, thoracolumbar region) , Neurological dysfunction (eg, vertebral fracture, spinal cord injury (contusion, laceration, amputation, etc.), nerve dysfunction due to compression of cauda equina due to spinal canal stenosis, acute Neurological dysfunction associated with transverse spinal cord injury, spinal disorder (eg, spondylosis, degenerative spinal disorder (degenerative spondylosis), osteoarthritis, recurrent atlantoaxial subluxation with myelopathy (myelopathy), spine Neurological dysfunction in tuberculosis, neuropathic spinal disorders, etc., and other spinal disorders (eg intervertebral disc disorder, intervertebral disc herniation), intervertebral disc degeneration, intervertebral disc rupture, intervertebral disc prolapse, cervical spondylosis, cervical arm syndrome Stability (symptoms), back pain, neck pain, sciatica, low back pain with sciatica, lower back pain, thoracic pain, radiculopathy, spinal cord disorder due to hematoma, progressive spinal cord disorder, etc.) , Spinal shock, Brown-Secart syndrome, etc., trunk and limb injuries (eg “thoracic injury”, “abdominal, lower back, lumbar and pelvic injury”, “shoulder and upper arm injury”, “elbow” And forearm injuries, wrist and hand injuries, hip and thigh injuries, knee and leg injuries, ankle and leg injuries, and other trunk, limb nerves, spinal nerves Neural dysfunction associated with root and plexus damage, etc., thorax injury (eg, thoracic spinal cord shaking and edema, thoracic spinal cord injury, thoracic spinal nerve root injury, thoracic peripheral nerve injury, thoracic sympathetic nerve) Nerve dysfunction associated with injury, etc., abdominal, lower back, lumbar and pelvic injury (eg, lumbar shaking and edema, lumbar injury, lumbar and sacral nerve root injury, cauda equina injury, lumbosacral) Plexus injury, lumbar, sacral and pelvic areas Neural dysfunction associated with sympathetic nerve injury, peripheral nerve injury in the abdomen, lower back and pelvis, etc., shoulder and upper arm injury (eg, ulnar nerve of the upper arm, median nerve, radial nerve injury, axillary nerve injury, myocutaneous nerve) Nerve dysfunction associated with injury, shoulder and upper arm skin sensory nerve damage, shoulder and upper arm multiple nerve injury, etc., elbow and forearm damage (eg, ulnar nerve of the forearm, median nerve, radial nerve injury, forearm skin) Neural dysfunction associated with sensory nerve damage, multiple forearm nerve damage, wrist and hand damage (eg wrist and hand ulnar nerve, median nerve, radial nerve damage, thumb finger nerve damage, other fingers Neurological dysfunction associated with finger nerve injury, wrist and hand multiple nerve injury, etc., hip and thigh damage (eg hip and thigh sciatic nerve, thigh nerve injury, hip and thigh skin knowledge) Neural dysfunction associated with nerve damage, multiple nerve damage in the hip and thigh, etc., knee and lower leg damage (eg, tibial nerve in the lower leg, radial nerve damage, cutaneous sensory nerve damage in lower leg, multiple nerve damage in lower leg) Etc.) neurological dysfunction, ankle and foot injury (eg, lateral plantar nerve injury, medial plantar nerve injury, deep ankle and deep peroneal nerve injury, cutaneous sensory nerve injury of ankle and foot, ankle and foot injury Nerve dysfunction associated with multiple nerve injuries, etc., neurological dysfunction associated with multi-site damage (eg, cranial nerve injury with cervical nerve and spinal cord damage, etc.) Dysfunction (eg, head injury (eg, superficial head injury, open head wound, skull and facial fractures, cranial nerve injury, eye and orbit injury, intracranial injury), neck and trunk injury (example Cervical and trunk superficial injuries and open wounds, vertebral fractures, other fractures of the thorax and pelvis, spinal cord injury, intrathoracic organ damage, intraperitoneal and pelvic organ damage), upper limb damage (e.g. Upper limb open wound, arm fracture, wrist and hand fracture, upper limb dislocation, sprain and strain, upper limb nerve injury, upper limb muscle and tendon injury, upper limb crush injury and traumatic amputation), lower limb injury ( For example, open wounds of the lower limbs, fractures of the femur, other fractures of the lower limbs, dislocation of the lower limbs, sprains and strains, nerve damage of the lower limbs, damage to the muscles and tendons of the lower limbs, crush injury of the lower limbs and
Neurological dysfunction that occurs as a secondary / sequelae of traumatic amputation), soft tissue disorders (eg, rheumatoid arthritis, myalgia, myalgia, neuralgia, neuritis or limb pain), inflammatory multiple joints Disorders (eg, neuropathic joint disorders), trauma during childbirth (eg, cranial nerves (eg, facial nerves), etc.) during peripheral birth, damage due to traction of the brachial plexus, etc. ) Associated with neurological dysfunction (eg, Elp palsy, Klumpke palsy, phrenic palsy due to injury at birth), perinatal disorders (eg, neonatal myotonia, transient neonatal myasthenia Disease, congenital hypertonia, Tomsen's disease, congenital hypotonia, other myotonic disorders in newborns), autonomic nervous system disorders (eg, idiopathic peripheral autonomic neuropathy, hereditary sensory autonomic neuropathy) -Familial autonomic dysfunction (Riley-Day syndrome), Horner syndrome, multiple systemic degeneration, autonomic neuropathy in endocrine and metabolic diseases, myelopathy in other diseases, etc.), neuromuscular junction diseases (eg, Myasthenia gravis, neonatal myasthenia, congenital myasthenia syndrome, ocular myasthenia gravis, and other neuromuscular disorders (eg, addiction (eg, botulinum addiction)) neuromuscular junction disease, drugs or toxins (E.g. cholinergic drugs, antibiotics, organophosphate insecticides, nerve gases, etc.), toxic neuromuscular transmission disorders, myasthenia syndrome in endocrine diseases, Eaton-Lambert syndrome, generalized tonic syndrome, Isaac syndrome , Myasthenia syndrome in neoplastic diseases such as myopathy, intermittent convulsions, pseudomuscular rigidity, cancer)), paralytic syndrome ( For example, motor paralysis, paraplegia and quadriplegia (eg, flaccid paraplegia, spastic paraplegia, flaccid quadriplegia, spastic quadriplegia, etc.), bilateral (side) paralysis of upper extremities, single paralysis of upper extremities, single paralysis of lower extremities , Other monoplegia, spastic paralysis of lower limbs, cauda equina syndrome, bilateral quadriplegia, contralateral hemiplegia, alternating hemiplegia, etc., muscular dystrophy (eg, primary myopathy (myogenic disease)) (Progressive muscular dystrophy, Duchenne muscular dystrophy, Becker muscular dystrophy, limb somatic muscular dystrophy, Emery-Drefus muscular dystrophy, distal muscular dystrophy (Miyoshi type / vacuum type), facial scapular brachial (Landugy Degerin) type muscular dystrophy Sexual (muscular tonic) muscular dystrophy, Steinert's disease, oropharyngeal muscular dystrophy, congenital muscular dystrophy Fee, Fukuyama type congenital muscular dystrophy, merosin-positive congenital muscular dystrophy, merosin-negative congenital muscular dystrophy , Centronuclear myopathy, nemarine myopathy, mitochondrial myopathy, infantile myopathy, inflammatory myopathy, other myopathy (eg, ophthalmo-pharyngeal distal myopathy, empty-type distal myopathy, infectious diseases (eg, trichinosis) Myopathy in endocrine disease, myopathy due to hypothyroidism, thyroid toxic myopathy, myopathy in metabolic disease, myopathy in hypercalcemia, myopathy in hypophosphatemia, Product-induced myopathy, alcoholic myopathy, myopathy caused by toxic substances, etc.), multisystem encephalomyopathy, progressive extraocular palsy, Kearns-Sayer syndrome, Melas (MERAS) syndrome, Murf (MERRF) syndrome, mitochondrial encephalomyopathy , Periodic limb paralysis, familial periodic paralysis, myoglobinuria, myositis (eg, interstitial myositis, traumatic ossifying myositis, progressive ossifying myositis, muscle paralytic calcification and ossification, bacteria Myositis in sexually transmitted diseases, myositis in protozoan and parasitic infections, myositis in sarcoidosis, etc., other myopathy (eg Cushing syndrome, acromegaly, immobility syndrome (paraplegic), muscle contracture, muscle wasting And atrophy, muscle strain, myotonia, congenital myotonia, Tomsen's disease, congenital myotosis, etc.) and systemic connective tissue disorders (eg Dermatomyositis (for example, juvenile dermatomyositis), polymyositis, other systemic connective tissue diseases (for example, rheumatic polymyalgia, skin (multiple) myositis in neoplastic diseases such as cancer), etc. ) And the like. Central nervous system diseases that cause motor dysfunction include, for example, extrapyramidal disorders and abnormal movement (eg Parkinson's disease, primary Parkinson's syndrome, secondary Parkinson's syndrome, juvenile Parkinson's syndrome, malignant syndrome, neuroleptic drugs) Malignant syndrome, drug-induced secondary Parkinson syndrome, post-encephalitic Parkinson syndrome, degenerative diseases of the basal ganglia (eg Hallerfolden-Spatz disease, progressive supranuclear (eye muscle) paralysis (Steel Richardson Orzewsky disease) ), Striatal substantia nigra degeneration), dyskinesia (abnormal movement), dystonia (dystonia) (eg drug-induced dystonia, idiopathic familial dystonia, idiopathic non-familial dystonia, systemic dystonia (deformation) Muscular dystonia), local dystonia, spastic torticollis, idiopathic orofacial dystonia, blepharospasm Medullary dystonia), other extrapyramidal disorders and abnormal movements (eg tremor (eg essential tremor, drug-induced tremor, resting tremor in Parkinson's disease, tremor in cerebellar disease, liver) Flapping tremor (fixed posture difficulty), intention tremor, periodic limb movement disorder, restless leg syndrome, etc., myoclonus (eg palatal myoclonus, progressive myoclonic epilepsy, operational myoclonus, head trauma or hypoxia) Myoclonus after bloody brain injury, Alzheimer's myoclonus, late-onset viral infection (eg, Creutzfeldt-Jakob disease, subacute sclerosing panencephalitis, etc.), myoclonus in uremia etc.), drug-induced chorea Chronic progressive chorea, hereditary chorea, other chorea-ataxia (eg, sedona Chorea (such as chorea, pregnancy-induced chorea), tics (eg drug-induced tics, organic tics), hereditary polytic disorder (Tulette syndrome), athetosis, choreoathetosis, hemiparism, etc.)), strain Atrophy (eg Huntington's disease (Huntington's chorea)), hereditary ataxia (eg congenital non-progressive ataxia, premature cerebellar ataxia, late cerebellar ataxia, disorder DNA Cerebellar ataxia with repair, hereditary spastic paraplegia, family antispasmodic paralysis, etc., spinal (progressive) muscular atrophy and related syndromes (for example, type 1 infantile spinal muscular atrophy (Weldnig Hoffman's disease), Waldhard Kugelberg-Werander disease, bulbar spinal muscular atrophy (Kennedy Alter Sunn syndrome), other hereditary spinal muscular atrophy), progression Neuromuscular atrophy, other motor neuron diseases (motor neuropathy, corticospinal tract, anterior horn cells and / or disorders of the medullary motor nucleus and associated diseases), primary lateral sclerosis, amyotrophic lateral cord Sclerosis (Lou Gehrig's disease), familial amyotrophic lateral sclerosis, progressive bulbar paralysis, progressive pseudospherical paralysis, neoplastic-related neuromyopathy and neuropathies (eg, neoplastic (tumor) associated syndrome, new Systematic atrophy that impairs the central nervous system in biological diseases, systemic atrophy that impairs the central nervous system in myxedema, etc.), neurodegenerative diseases (eg, Alzheimer's disease (early / late), limited) Cerebral atrophy (senile), senile brain degeneration, nervous system degeneration by alcohol, diffuse Lewy body disease, cortical basal ganglia degeneration, spinocerebellar degeneration, Friedreich ataxia, cerebellar ataxia , Multisystem atrophy, olive bridge cerebellar atrophy, Macquard Joseph disease (Zolea's motor system degeneration), Shy Dräger syndrome (cerebellar ataxia), late cerebellar cortical atrophy, familial spinocerebellar ataxia Dentate nuclei red nucleus pallidal Louis atrophy, Tay-Sachs disease (hexosaminidase A deficiency), subacute associated spinal degeneration, etc., demyelinating diseases (eg, multiple sclerosis, Acute disseminated demyelinating diseases (eg, optic neuromyelitis (Debic disease), acute and subacute hemorrhagic leukoencephalitis (Hurst), etc.), diffuse (pervasive) sclerosis, central demyelination of the corpus callosum, central bridge Myelinosis, generalized sclerosis, acute disseminated encephalomyelitis, acute cerebellar inflammation, transverse myelitis, acute transverse myelitis in demyelinating disease, subacute necrotizing myelitis, concentric sclerosis (Barrow) ), White matter dystrophy (eg, adrenoleukodystrophy) Etc.), interstitial and seizure disorders (eg, migraine (normal migraine without aura, classic migraine with aura), persistent migraine, headache syndrome (Eg, cluster headache syndrome, vascular headache, tension headache, chronic posttraumatic headache, drug-induced headache, etc.), transient cerebral ischemic attacks and related syndromes (eg, vertebral basilar artery syndrome, carotid syndrome ( Hemispheric), multiple and bilateral brain (parenchyma) external artery syndrome, transient cataract, etc.), cerebral vascular (sex) syndrome in cerebrovascular disease (eg middle cerebral artery syndrome, precerebrum) Nervous dysfunction associated with arterial syndrome, posterior cerebral artery syndrome, brainstem stroke syndrome, cerebellar stroke syndrome, pure motor multiple small infarction (Rakune) syndrome, pure sensory multiple small infarction (Rakune) syndrome, etc.), cerebral Paralysis (eg, spastic cerebral palsy) Numbness, spastic bilateral paralysis, hemiplegia in children, dyskinesia cerebral palsy, ataxic cerebral palsy, hemiplegia (eg flaccid hemiplegia, spastic hemiplegia, etc.), other disorders of the central nervous system ( Other brain disorders (eg hydrocephalus (eg traffic hydrocephalus, obstructive hydrocephalus, normal pressure hydrocephalus, post traumatic hydrocephalus, hydrocephalus in infectious diseases, hydrocephalus in neoplastic diseases such as cancer, etc.) ), Toxic encephalopathy, cerebral cyst, anoxic brain injury, benign intracranial hypertension, fatigue syndrome after viral infection, encephalopathy (encephalopathy, brain compression, cerebral edema, Reye syndrome, etc.), other disorders of the spinal cord (E.g., syringomyelia, medullary cavities, vascular myelopathy, spinal cord compression, acute spinal cord compression, subacute spinal cord compression, chronic spinal cord compression), cerebrospinal fluid leakage, meningopathies, post-treatment disorders of the nervous system (e.g. Cerebrospinal fluid leak from spinal tap, spine Response to lumbar puncture, hypocranial pressure secondary to ventricular shunt (low brain pressure), proteus syndrome, etc.) neurological dysfunction, central nervous system inflammatory disease (eg meningitis in infection) (Eg, bacterial meningitis (eg, H. influenzae meningitis, pneumococcal meningitis, streptococcal meningitis, staphylococcal meningitis, etc.), meningitis in viral diseases, mycosis Meningitis, etc.), other meningitis (eg non-suppurative meningitis, chronic meningitis, benign recurrent meningitis (morale meningitis), cancerous meningitis, etc.), encephalitis, Myelitis and encephalomyelitis (eg, acute disseminated encephalitis, tropical spastic paraplegia, bacterial meningoencephalitis and meningomyelitis, encephalitis, myelitis and infectious diseases (eg, bacterial disease, viral disease, etc.) Encephalomyelitis), intracranial (eg, epidural and subdural Nervous dysfunction due to abscesses and granulomas, intraspinal abscesses and granulomas, intracranial and intravertebral phlebitis and thrombophlebitis, etc., viral infections of the central nervous system (eg paralytic or non-paralytic) Acute gray leukomyelitis (polio), slow virus infection (eg, Creutzfeldt-Jakob disease, subacute sclerosing panencephalitis (SSPE), progressive multifocal leukoencephalopathy), enteroviral rash (Boston rash) ), Epidemic dizziness, Coxsackie virus infection, enterovirus infection, etc.) neurological dysfunction, viral infections of the central nervous system characterized by skin and mucosal lesions (eg herpes zoster, herpes zoster encephalitis, Neurological dysfunction due to herpes zoster meningitis, rubella (germanial measles, etc.), neurological dysfunction due to tuberculosis (eg tuberculosis meningitis, meningeal (sex) tuberculosis) Neurological dysfunction due to nuclear tumors), sexually transmitted infections (eg congenital syphilis (eg late congenital neurosyphilis (young juvenile neurosyphilis), etc.), late syphilis, overt neurosyphilis, asymptomatic nerves Nervous dysfunction caused by secondary or sequelae of neurological dysfunction due to syphilis, neurosyphilis, etc., central nervous system infections (eg, central nervous system tuberculosis, gray leukomyelitis (polio), leprosy, AIDS, viral encephalitis, etc.) (For example, post-polio syndrome, post-polio muscle atrophy, neuritis in leprosy, neuritis in AIDS, etc.), protozoal diseases of the central nervous system (eg, falciparum malaria with cerebral complications, chronic Chagas disease, etc.) Disorders, neurological dysfunction due to central nervous system helminthiasis (eg, central nervous system cysts), nutritional deficiencies (eg thiamine deficiency, vitamin B) ₁ Deficiency, vitamin B ₁₂ Neurological dysfunction (eg, deficiency)
For example, Wernicke encephalopathy (Encephalopathy), abetalipoproteinemia (Bassen-Kornzbike syndrome), etc., and other parts of the brain and central nervous system (for example, the cerebrum (excluding the cerebral lobe and ventricle, frontal lobe) Temporal lobe, parietal lobe, occipital lobe, ventricle, cerebellum, brain stem, brain border lesion), meninges (brain meninges, spinal cord membrane), spinal cord, horsetail, border lesions in other parts of the central nervous system, etc. ) Malignant neoplasms (eg brain tumors (eg astrocytomas, brain abscesses etc.)) or secondary malignant neoplasms, benign neoplasms of the central nervous system (eg central neurofibroma, hard Neurological dysfunction due to epidural abscess, subdural abscess, epidural tumor, meningioma (brain meningioma, spinal meningioma, etc.), cerebrovascular disease (eg, stroke, cerebral hemorrhage (eg, hypertensive brain) Internal hemorrhage, subarachnoid hemorrhage, subdural hemorrhage, epidural hemorrhage, etc. Cerebral infarction (eg, cerebral thrombus, cerebral embolism, etc.), transient cerebral ischemic attack, reperfusion injury, extracerebral artery occlusion and stenosis, cerebral artery occlusion and stenosis, non- (un) ruptured cerebral artery wall Sexual dissection, non- (un) ruptured cerebral aneurysm, cerebral artery atherosclerosis (symptom), progressive vascular leukoencephalopathy, hypertensive encephalopathy, moyamoya disease (Willis arterial occlusion), intracranial vein Systemic non-suppurative thrombosis, cerebral arteritis, cerebral amyloid angiopathy, cerebral arteritis in infectious diseases, blood loss shock, etc.), head injury (eg, intracranial injury) of the central nervous system , Shaking, traumatic brain edema, diffuse brain injury, focal brain injury, epidural hemorrhage, traumatic subdural hemorrhage, traumatic subarachnoid hemorrhage, cerebral contusion, penetration, shear, compression, laceration, delivery Neurological dysfunction associated with trauma, infant whiplash sway syndrome, etc., spinal column (occipital ring) Central nervous system neurological dysfunction (eg, vertebral fracture, spinal cord injury (contusion, laceration, separation) in shaft, neck, cervico-thoracic, thoracic, thoracolumbar, lumbar, lumbosacral, sacral and sacroiliac) disorders ), Neurological dysfunction associated with acute transverse spinal cord injury, spinal disorder (eg, spondylosis, spinal canal stenosis, degenerative spinal disorder (degenerative spondylosis), osteoarthritis, myelopathy (myelopathy) Nerve dysfunction in recurrent atlantoaxial subluxation, spinal tuberculosis, neuropathic spondylopathy, etc., nerve dysfunction due to compression of the caudad nerve due to spinal canal stenosis, other spinal disorders (eg, intervertebral disc disorders, disc herniation (medullary spinal cord)) Nuclear hernia), disc degeneration, disc rupture, disc prolapse, cervical spondylosis, cervical arm syndrome, spinal instability, back pain, neck pain, sciatica, low back pain with sciatica, lower back pain, thoracic vertebra pain, Radiculopathy, blood Neurological dysfunction in spinal cord disorders, progressive spinal cord disorders, etc.), spinal shock, Brown-Sekar syndrome, etc., maternal disorders related to pregnancy (eg, anesthesia complications during pregnancy (eg, anesthesia-related central Neurological complications, toxic reactions to local anesthesia, spinal or epidural anesthesia-induced headaches, etc.)), neurological dysfunction (eg, chorea, etc.), and neurological dysfunction (eg, delivery)・ Neuronal dysfunction associated with anesthesia complications in postpartum (eg, central nervous system complications of anesthesia, toxic response to local anesthesia, spinal anesthesia and epidural anesthesia-induced headaches, etc.), trauma at birth (eg, CNS nervous system due to damage at birth of the central nervous system (for example, brain edema due to damage at birth, brain injury due to damage at birth, spinal and spinal cord damage at birth), etc. Disorders, perinatal disorders (eg, neonatal brain abnormalities (eg, neonatal cerebral ischemia, neonatal acquired periventricular cysts, neonatal brain white matter softening, neonatal brain irritability, neonatal brain) Neurological dysfunction, drugs, drugs and biologicals (eg, systemic antibiotics, systemic antiinfectives, antiparasitic drugs, hormones, synthetic substitutes and antagonists thereof) Non-opioid analgesics, antipyretic drugs, antirheumatic drugs, narcotics, psychopathic drugs (halogens), anesthetics, therapeutic gases, antiepileptic drugs, sedative / hypnotic drugs, antiparkinsonian drugs, psychotropic drugs, Drugs mainly acting on the autonomic nervous system, drugs mainly acting on the whole body and blood, drugs acting mainly on the cardiovascular system, drugs acting mainly on the digestive system, drugs acting mainly on the smooth muscle, skeletal muscle and respiratory system , main By topical drugs, ophthalmic drugs, otolaryngology drugs and dental drugs, diuretics, other drugs, drugs and biologics etc.) and / or its secondary / sequelae Nerve dysfunctions that occur, non-medicinal substances (eg alcohols, organic solvents, aliphatic and aromatic hydrocarbon halogen derivatives, corrosive substances, soaps, detergents, metals (lead, organic mercury, etc.), other Inorganic substances (arsenic, cadmium, etc.), carbon monoxide, other gases (sarin, soman, tabun, VX gas, etc.), fumes and vapors, pesticides, harmful substances ingested as seafood, other ingested as food Toxic effects (addiction) of harmful substances, contact with toxic animals, food contaminants such as aflatoxins and other fungal toxins (mycotoxins, etc.) and / or Or neurological dysfunction caused by its sequelae and sequelae, and other (eg, radiation, heat, light, atmospheric pressure or water pressure) effects (eg, thermal syncope, thermal (convulsive) convulsions, ear pressure trauma, sinus) And / or neurological dysfunction caused by its subsequent / sequelae, etc.). Other symptoms and signs considered to be motor dysfunction include, for example, numbness, pain and neuropathic pain (eg, numbness, acute pain, acute postoperative pain, postoperative pain syndrome (eg, postmastectomy syndrome, discontinuation) End pain etc.), chronic pain, chronic intractable pain (allodynia), peripheral neuropathic pain, cancer pain, neuropathic pain syndrome, painful traumatic mononeuropathy, painful polyneuropathy, diabetic peripheral nerve Disability pain, central pain syndrome, complex regional pain syndrome, reflex sympathetic dystrophy, burning pain, phantom limb pain, causalgia, Ramsey Hunt syndrome, etc., symptoms and signs related to the nervous system and musculoskeletal system (eg abnormal involuntary movements) (Dyskinesia) (eg abnormal head movements, tremors, (painful) convulsions, muscle fiber bundle spasms, periodic limb movement disorders, restless legs syndrome, etc.) Abnormal gait and movement (eg, ataxic gait, paralytic gait, difficulty walking), other coordination disorders (eg, ataxia, cerebellar ataxia (Shy-Drager syndrome), telangiectasia) ), Other symptoms and signs related to the nervous system and musculoskeletal system (eg, tetany, meningitis), abnormal reflexes, abnormal extensor reflexes of the sole, Babinsky signs, abnormal posture, hip click, spasticity , Hypertonia, myotonia, deep tendon reflexes, hypotonia, myalgia, dysphagia, gaze crisis, etc.), skin and subcutaneous tissue symptoms and signs (eg skin sensory disorders (eg skin Perception (sensory) loss, decline, abnormality (symptoms), glove-type sensory impairment, tinel symptom (interference), perception (sensory) hypersensitivity, tactile hypersensitivity, hyperalgesia, etc.), conversation and sound Symptoms and signs (eg, speech disorders (eg, aphasia, aphasia, dysarthria, ataxia, etc.), voice disorders (eg, dysphonia (difficult to speak), loss of speech (impaired speech), high nose and Low nasal sounds, etc.), speech and language specific developmental disorders (eg, specific speech dysarthria, expressive language disorder, receptive language disorder, acquired aphasia with epilepsy (Landau-Kreffner syndrome) etc.)), Symptoms and signs related to cognition, perception, emotional state and behavior (eg, dizziness, staggering, olfactory disturbances (eg, no smell, olfactory illusion), taste disorders (eg, gustatory illusion) )), Other symptoms and signs of general sensation and perception (eg, hallucinations, hallucinations, other hallucinations, etc.), specific developmental disorders of motor function), childhood, childhood and adolescence Onset of behavioral and emotional disorders (eg, tic disorders (eg, transient tic disorders, chronic motility or voice tic disorders, tic disorders that include both voice and polymotility (Jill de la Toe Rett syndrome, etc.), behavioral and emotional disorders that usually develop in childhood (childhood) and adolescence (for example, stereotypic movement disorders, stuttering, premature (messy) linguistics, etc.) and the like.

  The agent of the present invention can be applied to mammals (human and non-human animals (eg, monkeys, sheep, cows, horses, dogs, cats, rabbits, rats, mice, etc.)) and the like. In particular, preferred preventive, therapeutic and / or progression-inhibiting effects on motor dysfunction can be obtained by systemic or local administration to mammals, preferably humans, by oral or parenteral administration. It can also be administered surgically, for example, directly into the ventricle.

  The dose of the drug of the present invention varies depending on age, body weight, symptom, therapeutic effect, administration method, treatment time, and the like, but in the case of oral administration, (2R) -2-propyloctane is usually per person per adult. The acid is orally administered once to several times a day in the range of 1 μg to 5000 mg, preferably 50 mg to 1500 mg, more preferably 300 mg to 1500 mg. In the case of parenteral administration, per adult, once per day, in the range of 0.1 ng to 500 mg, preferably 0.5 mg to 25 mg as (2R) -2-propyloctanoic acid per kg body weight. Is administered parenterally. The parenteral dosage form is preferably intravenous administration and is continuously administered intravenously in the range of 1 hour to 24 hours per day. Of course, since the dose varies depending on various conditions, a dose smaller than the above dose may be sufficient, or administration beyond the range may be necessary.

  When the drug of the present invention is administered, it is used as a solid preparation for internal use for oral administration, a liquid preparation for internal use, an injection for parenteral administration, an external preparation and the like.

  Examples of solid preparations for internal use for oral administration include tablets, pills, capsules, powders, fine granules, granules and the like. Tablets include sublingual tablets, buccal adhesive tablets, buccal quick disintegrating tablets and the like. Capsules include hard capsules and soft capsules.

  In such a solid preparation for internal use, the drug is used as it is or an excipient (for example, lactose, mannitol, glucose, microcrystalline cellulose, starch, sucrose, sorbit, talc, cyclodextrin, etc.), a binder (for example, Hydroxypropylcellulose, polyvinylpyrrolidone, magnesium aluminate metasilicate, cellulose, methylcellulose, gelatin, gum arabic, polyethylene glycol, sucrose, starch, etc.), disintegrants (for example, calcium calcium glycolate, starch, carboxymethylcellulose, carboxymethylcellulose) Calcium salt, etc.), lubricants (eg, magnesium stearate, talc, etc.), stabilizers, solubilizing agents (eg, glutamic acid, aspartic acid, etc.), etc. It used Te. Moreover, you may coat | cover with a coating agent (For example, sucrose, gelatin, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate etc.) as needed, and you may coat | cover with two or more layers. Also included are capsules of absorbable substances such as gelatin.

  The sublingual tablet is prepared according to a known method. For example, drugs (for example, lactose, mannitol, glucose, microcrystalline cellulose, colloidal silica, starch, etc.), binders (for example, hydroxypropylcellulose, polyvinylpyrrolidone, magnesium aluminate metasilicate, etc.), disintegrants ( For example, starch, L-hydroxypropyl cellulose, carboxymethyl cellulose, croscarmellose sodium, calcium calcium glycolate, etc.), lubricant (eg, magnesium stearate), swelling agent (eg, hydroxypropyl cellulose, hydroxypropyl methylcellulose) , Carbopol, carboxymethylcellulose, polyvinyl alcohol, xanthan gum, guar gum, etc.), swelling aids (eg glucose, fructose, mannitol, xylates) Erythritol, maltose, trehalose, phosphate, citrate, silicate, glycine, glutamic acid, arginine, etc.), stabilizer, solubilizer (eg, polyethylene glycol, propylene glycol, glutamic acid, aspartic acid, etc.) , Flavoring agents (for example, orange, strawberry, mint, lemon, vanilla, etc.) and the like, and formulated into a conventional method for use. Moreover, you may coat | cover with a coating agent (For example, sucrose, gelatin, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate etc.) as needed, and you may coat | cover with two or more layers. Moreover, additives such as preservatives, antioxidants, colorants, sweeteners and the like that are commonly used can be added as necessary.

  The intraoral patch is prepared according to a known method. For example, drugs (for example, lactose, mannitol, glucose, microcrystalline cellulose, colloidal silica, starch, etc.), binders (for example, hydroxypropylcellulose, polyvinylpyrrolidone, magnesium aluminate metasilicate, etc.), disintegrants ( For example, starch, L-hydroxypropyl cellulose, carboxymethyl cellulose, croscarmellose sodium, calcium calcium glycolate, etc.), lubricant (eg, magnesium stearate), adhesive (eg, hydroxypropyl cellulose, hydroxypropyl methylcellulose) , Carbopol, carboxymethylcellulose, polyvinyl alcohol, xanthan gum, guar gum, etc.), adhesion aids (eg glucose, fructose, mannitol, xylates) Erythritol, maltose, trehalose, phosphate, citrate, silicate, glycine, glutamic acid, arginine, etc.), stabilizer, solubilizer (eg, polyethylene glycol, propylene glycol, glutamic acid, aspartic acid, etc.) , Flavoring agents (for example, orange, strawberry, mint, lemon, vanilla, etc.) and the like, and formulated into a conventional method for use. Moreover, you may coat | cover with a coating agent (For example, sucrose, gelatin, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate etc.) as needed, and you may coat | cover with two or more layers. Moreover, additives such as preservatives, antioxidants, colorants, sweeteners and the like that are commonly used can be added as necessary.

  The intraoral quick disintegrating tablet is prepared according to a known method. For example, the drug is coated as it is or with an appropriate coating agent (for example, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, acrylic acid / methacrylic acid copolymer), or a plasticizer (for example, polyethylene glycol, triethyl citrate). To the drug substance powder or granulated powder particles subjected to the treatment, excipients (for example, lactose, mannitol, glucose, microcrystalline cellulose, colloidal silica, starch, etc.), binders (for example, hydroxypropyl cellulose, polyvinylpyrrolidone, Magnesium aluminate metasilicate), disintegrating agents (eg starch, L-hydroxypropylcellulose, carboxymethylcellulose, croscarmellose sodium, calcium calcium glycolate), lubricants For example, magnesium stearate), dispersion aid (for example, glucose, fructose, mannitol, xylitol, erythritol, maltose, trehalose, phosphate, citrate, silicate, glycine, glutamic acid, arginine, etc.), stabilizer , Mixed with solubilizing agents (eg, polyethylene glycol, propylene glycol, glutamic acid, aspartic acid, etc.), flavoring agents (eg, orange, strawberry, mint, lemon, vanilla, etc.), etc. Moreover, you may coat | cover with a coating agent (For example, sucrose, gelatin, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate etc.) as needed, and you may coat | cover with two or more layers. If necessary, additives such as commonly used preservatives, antioxidants, colorants, sweeteners and the like can be added.

  Soft capsules for oral administration (hereinafter sometimes abbreviated as “capsules of the present invention”) can be produced according to known methods for producing soft capsules. Specifically, the drug and the film solution are further subjected to a known capsule filling method such as a punching method (for example, a rotary die method) or a dropping method (for example, a seamless capsule method), and further obtained. Can be produced by drying the capsules. The capsule of the present invention may be a seamless soft capsule or a soft capsule with a seam. The method for producing the seamless capsule is described in detail in known literature, for example, Bioscience and Industry, Vol. 58, No. 7, pages 31 to 34 (2000 publication). Since this basic seamless capsule manufacturing method is already used industrially, mass production is easy.

  The capsule of this invention is comprised by the content liquid and the capsule membrane | film | coat like a general soft capsule. Capsule film is the main substance of capsule film called protein base (protein (gelatin, collagen, etc.)), polysaccharide (starch, amylose, polygalacturonic acid, agar, carrageenan, gum arabic, gellan gum, xanthan gum, pectin, alginic acid Etc.), biodegradable plastics (polylactic acid, polyhydroxybutyric acid, polyglutamic acid, etc.), hardened fats and oils (triglycerides and diglycerides of medium chain fatty acids such as butter, margarine, shortening, cocoa butter, etc.) and plasticizers (glycerin) , Sugars such as sorbitol and polyethylene glycol, sugar alcohols, polyhydric alcohols, etc.) and essential ingredients such as mint, cinnamon oil, strawberry and other fruit essences and flavors, and preservatives (parahydroxy benzoate) Acid , Para-hydroxybenzoic acid propyl, etc.), pigment (yellow 4, yellow 5, red 3, blue 1, copper chlorofin, etc.), opacifier (titanium dioxide, bengara etc.), solubility regulator (cellulose) Acetate phthalate, alkali metal salt of hydroxypropylmethylcellulose, alkali metal salt of hydroxymethylcellulose acetate succinate, alkali metal alginate, alkali metal polyacrylate, methylcellulose, carboxymethylcellulose, casein, collagen, agar powder, polyvinyl alcohol, pectin, etc. ) And the like.

  In the capsule of the present invention, the capsule film is preferably based on gelatin. Particularly preferred are those based on gelatin and containing glycerin as a plasticizer. Further, sorbitol may further be included as a plasticizer.

  The capsule film can be produced using a film solution. The film solution contains the above-described film components, and can be formed into a thin film in the molten state or in the solution state, and further solidified by cooling and / or drying after the film is formed. It can be used without particular limitation.

  The additive is not particularly limited as long as it is an additive generally used for preparations for oral administration. For example, additives used for soft capsule preparations and oral liquids are preferable, for example, preservatives, preservatives, interfaces. Activators, solubilizers, emulsifiers, solvents, pH adjusters, buffers, suspending agents, thickeners, stabilizers, solubilizers and the like are used. These additives can be added in combination of two or more components as desired. Examples of preservatives and preservatives include benzoic acid, sodium benzoate, sodium sorbate, parabens (ethyl paraoxybenzoate, butyl paraoxybenzoate, propyl paraoxybenzoate, etc.) and the like. Examples of the surfactant, solubilizer, emulsifier, and solvent include hydroxypropylmethylcellulose, polyvinylpyrrolidone, sucrose fatty acid ester, polyoxyethylene hydrogenated castor oil, polysorbate 80, polyethylene glycol, glycerin, ethanol, propylene glycol, water (For example, distilled water for injection, etc.). Examples of pH regulators and buffers include inorganic acids or bases such as alkali, such as hydrochloric acid, sodium hydroxide, potassium hydroxide, sodium hydrogen carbonate, and organic acids such as citric acid, malic acid, tartaric acid or succinic acid. Examples thereof include acids or salts thereof. The pH may be adjusted according to a method for adjusting pH generally used in the technical field of oral liquid preparations or a method analogous thereto. Examples of the suspending agent and thickening agent include gum arabic, crystalline cellulose, bee gum, xanthan gum, gelatin, metrose and its edible salt, carmellose and its edible salt, and the like. Examples of the stabilizer include edible salts of edetic acid, sodium chloride, edible salts of pyrosulfite, and the like. Examples of the solubilizer include cyclodextrin and arginine. These additives are generally blended in proportions usually used for oral preparations. In addition to the above, additives such as those described in publicly known documents such as “Pharmaceutical Additives Dictionary” (edited by Japan Pharmaceutical Additives Association) published in 2000 by Yakuji Nippo may be used.

  Liquid preparations for internal use for oral administration include solutions, suspensions, emulsions, syrups, elixirs and the like. In such a liquid preparation, the drug is prepared by dissolving, suspending or emulsifying in a commonly used diluent (for example, purified water, ethanol or a mixture thereof). Furthermore, this liquid agent may contain a wetting agent, a suspending agent, an emulsifier, a sweetening agent, a flavoring agent, a fragrance, a preservative, a buffering agent and the like.

  The injection for parenteral administration includes all injections. For example, an injection for muscle, an injection for intravenous injection, an intravenous infusion, and the like are included.

Infusion preparations and injections for parenteral administration include (2R) -2-propyloctanoic acid, its salts, solvates or prodrugs thereof, and metal salts generally used for injections ( For example, trisodium phosphate, disodium monohydrogen phosphate, sodium carbonate, sodium sulfite, etc.) and pH regulators (eg, sodium hydroxide), stabilizers, surfactants, buffers, solubilizers , Antioxidants, antifoaming agents, isotonic agents, emulsifiers, suspending agents, preservatives, soothing agents, solubilizers, solubilizers, etc. (For example, distilled water for injection, physiological saline, vegetable oil, propylene glycol, polyethylene glycol, alcohols such as ethanol, etc.) It can be prepared by dissolving these combinations, etc.). In the case of infusion preparations, in addition to these additives, electrolytes (for example, sodium chloride, potassium chloride, calcium chloride, sodium lactate, sodium dihydrogen phosphate, sodium carbonate, magnesium carbonate, etc.), sugars (for example, glucose) , Fructose, sorbitol, mannitol, dextran, etc.), protein amino acids (eg, glycine, aspartic acid, lysine, etc.), vitamins (eg, vitamin B ₁ , vitamin C, etc.), etc. Can be used. Such a pharmaceutical composition is sterilized in the final step or manufactured and prepared by an aseptic operation method. In addition, an aseptic solid preparation, for example, a freeze-dried product, can be produced and dissolved before use in a sterilized or aseptically sterilized purified water or other solvent.

  Examples of external preparations for parenteral administration include ointments, gels, creams, poultices, patches, liniments, sprays, sprays, inhalants, eye drops, nasal drops, ear drops Etc. are included. These are prepared by a known method or a commonly used formulation.

  The ointment is prepared by a known or commonly used formulation. For example, the drug is prepared by mixing or melting the base. The ointment base is selected from known or commonly used ones. For example, higher fatty acids or higher fatty acid esters (for example, adipic acid, myristic acid, palmitic acid, stearic acid, oleic acid, adipic acid ester, myristic acid ester, palmitic acid ester, stearic acid ester, oleic acid ester, etc.), waxes (E.g., beeswax, whale wax, ceresin, etc.), surfactants (e.g., polyoxyethylene alkyl ether phosphates, etc.), higher alcohols (e.g., cetanol, stearyl alcohol, cetostearyl alcohol, etc.), silicone oils (e.g., Dimethylpolysiloxane, etc.), hydrocarbons (eg, hydrophilic petrolatum, white petrolatum, purified lanolin, liquid paraffin, etc.), glycols (eg, ethylene glycol, diethylene glycol, propylene glycol, polyethylene) Recall, macrogol, etc.), vegetable oil (eg, castor oil, olive oil, sesame oil, turpentine oil, etc.), animal oil (eg, mink oil, egg yolk oil, squalane, squalene, etc.), water, absorption enhancer, anti-rash agent Can be used alone or in admixture of two or more. Furthermore, a humectant, a preservative, a stabilizer, an antioxidant, a flavoring agent and the like may be included.

  The gel is prepared by a known or commonly used formulation. For example, it is prepared by melting a drug in a base. The gel base is selected from known or commonly used ones. For example, lower alcohol (eg, ethanol, isopropyl alcohol, etc.), gelling agent (eg, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, ethylcellulose, etc.), neutralizing agent (eg, triethanolamine, diisopropanolamine, etc.), Those selected from surfactants (for example, polyethylene glycol monostearate), gums, water, absorption promoters and anti-rash agents are used alone or in admixture of two or more. Furthermore, a preservative, an antioxidant, a flavoring agent and the like may be included.

  The cream is prepared by a known or commonly used formulation. For example, it is prepared by melting or emulsifying a drug in a base. The cream base is selected from known or commonly used ones. For example, higher fatty acid esters, lower alcohols, hydrocarbons, polyhydric alcohols (eg, propylene glycol, 1,3-butylene glycol, etc.), higher alcohols (eg, 2-hexyldecanol, cetanol, etc.), emulsifiers (eg, polyoxy (Ethylene alkyl ethers, fatty acid esters, etc.), water, absorption accelerators, and rash prevention agents may be used alone or in admixture of two or more. Furthermore, a preservative, an antioxidant, a flavoring agent and the like may be included.

  The poultice is prepared by a known or commonly used formulation. For example, it is prepared by melting a drug in a base, spreading it onto a support as a kneaded product. The poultice base is selected from known or commonly used ones. For example, thickeners (for example, polyacrylic acid, polyvinylpyrrolidone, gum arabic, starch, gelatin, methylcellulose, etc.), wetting agents (for example, urea, glycerin, propylene glycol, etc.), fillers (for example, kaolin, zinc oxide, Talc, calcium, magnesium, etc.), water, solubilizers, tackifiers and anti-rash agents are used alone or in admixture of two or more. Furthermore, a preservative, an antioxidant, a flavoring agent and the like may be included.

  The patch is prepared by a known or commonly used formulation. For example, it is prepared by melting a drug in a base and spreading it on a support. The base for patch is selected from known or commonly used ones. For example, those selected from polymer bases, oils and fats, higher fatty acids, tackifiers and anti-rash agents may be used alone or in admixture of two or more. Furthermore, a preservative, an antioxidant, a flavoring agent and the like may be included.

  The liniment is prepared by a known or commonly used formulation. For example, a drug selected from water, alcohol (eg, ethanol, polyethylene glycol, etc.), higher fatty acid, glycerin, soap, emulsifier, suspending agent, etc. alone, or dissolved, suspended or emulsified in two or more kinds Prepared. Furthermore, a preservative, an antioxidant, a flavoring agent and the like may be included.

  Sprays and sprays include buffers that provide isotonicity with stabilizers such as sodium bisulfite in addition to commonly used diluents, such as sodium chloride, sodium citrate or citric acid, etc. It may contain a tonicity agent.

  Inhalants for parenteral administration include aerosols, inhalable powders or inhalable solutions, which are used by dissolving or suspending them in water or other suitable media at the time of use. It may be. These inhalants are prepared according to known methods. For example, in the case of inhalation solutions, preservatives (eg, benzalkonium chloride, parabens, etc.), colorants, buffering agents (eg, sodium phosphate, sodium acetate, etc.), isotonic agents (eg, chloride) Sodium, concentrated glycerin, etc.), thickeners (for example, cariboxyvinyl polymer, etc.), absorption accelerators, and the like are appropriately selected as necessary. In the case of powders for inhalation, lubricants (for example, stearic acid and its salts), binders (for example, starch, dextrin, etc.), excipients (for example, lactose, cellulose, etc.), colorants, antiseptics An agent (for example, benzalkonium chloride, paraben, etc.), an absorption accelerator and the like are appropriately selected as necessary. A nebulizer (for example, an atomizer, a nebulizer, etc.) is usually used when administering an inhalation solution, and an inhalation administration device for powdered drugs is usually used when administering an inhalable powder.

  As other dosage forms for parenteral administration, suppositories for rectal administration, pessaries for intravaginal administration, etc. prescribed by conventional methods are used.

  The specific dosing period in the drug of the present invention is, for example, preferably 1 day to 5 years, preferably 1 day to 1 year, more preferably 1 day to 6 months, etc. for oral administration. For one day to two months. For parenteral administration, for example, intravenous administration, 1 day to 100 days, etc., preferably 1 day to 10 days, etc., more preferably 1 day to 7 days, etc., most preferably 7 days, etc. are mentioned. .

  The agent of the present invention is (1) supplementation and / or enhancement of the prevention, treatment and / or progression inhibitory effect of the compound, (2) kinetics / absorption improvement, dose reduction, and / or (3) reduction of side effects. Therefore, it may be administered as a concomitant drug in combination with other drugs.

  The concomitant agent of the drug of the present invention and another drug (hereinafter sometimes abbreviated as the concomitant drug of the present invention) may be administered in the form of a combination drug containing both components in one preparation, In addition, it may take the form of administration as separate preparations. When administered as separate preparations, they may be administered simultaneously or at a time difference. In addition, when administered at a time difference, (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof or a prodrug thereof may be administered first, and a concomitant drug may be administered later. The concomitant drug may be administered first, and (2R) -2-propyloctanoic acid, its salt, its solvate or their prodrugs may be administered later, each administration method, number of administrations per day May be the same or different. The weight ratio of (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof or a prodrug thereof and a concomitant drug is not particularly limited.

  The disease that exerts a preventive, therapeutic and / or progress-inhibiting effect by the combination agent of the present invention is not particularly limited, and the preventive, therapeutic and / or progress-inhibiting effect is complemented and / or compared with the case where the drug is administered alone. Alternatively, it may be any disease that enhances, improves pharmacokinetics / absorption, reduces the dose / side effects of a drug, or prevents the development of drug resistance.

Other drugs used in the combination of the present invention include, for example, cerebrovascular disorders (eg, stroke, cerebral infarction (eg, cerebral thrombosis, cerebral embolism, etc.), transient cerebral ischemic attack, reperfusion injury, cerebral hemorrhage ( Eg, hypertensive intracerebral hemorrhage, subarachnoid hemorrhage etc.), therapeutic agents for brain tumors (eg astrocytoma, brain abscess etc.), hypotensive shock, traumatic shock, head injury and / or Drugs for neurological dysfunction associated with cerebrospinal trauma (eg, brain contusion, penetration, shear, compression, laceration, labor trauma, infant whiplash syndrome, etc.), neurodegenerative diseases (eg, Parkinson's disease, Parkinson's syndrome, striatum) Corpus nigra degeneration, Huntington's disease, chorea-ataxia, progressive supranuclear palsy, diffuse Lewy body disease, cortical basal ganglia degeneration, Alzheimer's disease, senile dementia (dementia), Pick disease The frontal side Leaf type dementia (dementia), familial dementia (dementia), spinocerebellar degeneration (eg, olive bridge cerebellar atrophy, late-onset cerebellar cortical atrophy, familial spinocerebellar ataxia (eg, Maccard) Joseph's disease, etc.), dentate nuclei, red nuclei, Ryukyu atrophy, familial spastic paraplegia, Friedreich's disease, etc.), therapeutic neuromotor disease (eg, amyotrophic lateral sclerosis, family) Therapeutic agents for degenerative amyotrophic lateral sclerosis, etc., demyelinating diseases (eg, multiple sclerosis, generalized sclerosis, acute disseminated encephalomyelitis, acute cerebellar inflammation, transverse myelitis, Guillain Valley) Syndrome, etc.), cerebrospinal diseases associated with infectious diseases (eg meningitis, influenza encephalopathy, Creutzfeldt-Jakob disease, dementia due to AIDS encephalopathy (dementia), etc.), toxic substances (arsenic, cadmium, Organic mercury, sarin, soman, tabun, VX gas, etc.) / Radiation Remedies for neurological dysfunction, etc., remedies for mental disorders (eg neurosis, psychosomatic disorders, anxiety, schizophrenia, mania, depression, etc.), epilepsy, mage syndrome, dystonia, Down syndrome and / or sleep disorders ( For example, treatment for hypersomnia, narcolepsy, sleep apnea syndrome, etc., treatment for diabetes and / or diabetic complications, treatment for hyperlipidemia, dopamine receptor agonist (dopamine receptor stimulant), dopamine Release enhancer (dopamine secretion enhancer or dopamine release enhancer), dopamine uptake inhibitor, dopaminergic agent, central anticholinergic agent, aromatic L-amino acid decarboxylase inhibitor (DCI), monoamine oxidase (MAO-) B) Inhibitors, catechol-O-methyltransferase (COMT) inhibitors, norepinephrine (noradrenaline) supplements, acetyl Cholinesterase inhibitor, NMDA (N-methyl-D-aspartate) receptor antagonist, AMPA (2-amino-3- (methyl-3-hydroxyisoxazol-4-yl) propanoic acid) / kainate receptor antagonist Drugs, GABA _A receptor modulators (eg, GABA _A receptor agonists, etc.), GABA _B receptor modulators, adenosine A2A receptor blockers, nicotine receptor modulators, neuronal nitric oxide synthase (n- NOS) inhibitor, β amyloid protein production, secretion, accumulation, aggregation and / or deposition inhibitor (eg, β secretase inhibitor, γ secretase inhibitor, β amyloid protein aggregation inhibitor, β amyloid degrading enzyme, β amyloid) Vaccines, etc.), apoptosis inhibitors, neuronal differentiation and / or regeneration promoters, neurotrophic factors (eg, new Trophin, TGF-β superfamily, neurocaine family, growth factors, etc.), other brain function activators (eg, brain metabolism activators, cerebral circulation improvers, etc.), Rho-kinase inhibitors, antihypertensives, diuretics, β receptor blocker, calcium channel blocker (calcium antagonist), angiotensin converting enzyme (ACE) inhibitor, angiotensin II receptor antagonist, sodium channel blocker, potassium channel opener, antiplatelet agent, anticoagulant, Thrombolytic agent, thromboxane A ₂ synthase inhibitor, matrix metalloproteinase (MMP) inhibitor, cyclooxygenase (COX) -2 inhibitor, nonsteroidal anti-inflammatory drug, steroid drug, antioxidant drug, vitamins, disease modification Anti-rheumatic drugs, anti-cytokine drugs (eg TNF inhibitors, MAP kinas) Such as progesterone, estradiol, estradiol benzoate, parathyroid hormone (eg, PTH), factor Xa inhibitor, factor VIIa inhibitor, glycerin preparation, etc. 1 type or 2 types or more of these drugs, or those compounding agents.

  In the present specification, examples of the therapeutic agents for stroke include alteplase, argatroban, citicoline, clopidogrel hydrogen sulfate, DMP-647, dipyridamole, and idebenone. ), Indobufen, monosialoganglioside GM1 (monosialoganglioside GM1), nimodipine, propentofylline, triflusal, monteplase, aspirin, nicotinic acid , Sodium ozagrel.

  In this specification, the therapeutic agents for cerebral infarction include, for example, citicoline, edaravone, ibudilast, triflusal, cilostazol, nicaraven, sodium ozagrel ).

  In the present specification, examples of therapeutic agents for cerebral thrombosis include ozagrel, sodium ozagrel, ticlopidine, ticlopidine hydrochloride, fasudil, tissue plasminogen activator (t -PA), alteplase, synthetic antithrombin drugs (gabexate mesylate, nafamostat mesylate, etc.).

  In the present specification, examples of the therapeutic agent for subarachnoid hemorrhage include monosialoganglioside GM1 (monosialoganglioside GM1), tirilazad mesylate, nicaraven, and sodium ozagrel.

  In the present specification, examples of the preventive, therapeutic and / or symptom progression inhibitory agents for Parkinson's disease and / or Parkinson's syndrome include, for example, levodopa (L-dopa), levodopa benserazide (levodopa + benserazide, eg levodopa) -Benserazide (4: 1) formulation), levodopa carbidopa formulation (levodopa + carbidopa, for example, levodopa carbidopa (10: 1) formulation, levodopa carbidopa (4: 1) formulation), bromocryptine mesylate (bromocryptine mesylate), alpha-dihydroergocryptine, cabergoline, droxidopa, pergolide mesylate, pramipexole, pramipexole hydrochloride hydrate, selegiline hydrate (Selegiline), Talipexo Le (talipexole), amantadine hydrochloride (amantadine hydrochloride), include trihexyphenidyl hydrochloride (trihexyphenidyl hydrochloride) is.

  In the present specification, examples of the therapeutic agent for Huntington's disease include riluzole, LAX-101, tetrabenazine, olanzapine, and glatiramer acetate.

  In the present specification, examples of the therapeutic agent for chorea-ataxia include taltirelin, NS-2330, T-2000, and talampanel.

  In the present specification, as a therapeutic agent for Alzheimer's disease, for example, α-dihydroergocryptine, donepezil hydrochloride, fraction F (Fraction F), galantamine, indeloxazine ( indeloxazine, memantine hydrochloride, nicergoline, phosphatidylserine, rivastigmine tartrate, ST-200, tacrine, cerebrolysin, hypererine A, huperzine A An example is nefiracetam.

  In this specification, as a therapeutic agent for senile dementia (dementia), for example, ST-200, zuclopenthixol acetate (zuclopenthixol acetate), zuclopenthixol decanoate (zuclopenthixol decanoate), cerebrolysin ( Cerebrolysin) and nefiracetam.

  In the present specification, as a therapeutic agent for amyotrophic lateral sclerosis, for example, riluzole, edaravone, xaliproden hydrochloride, TCH-346, superoxide dismutase, pen An example is pentoxifylline.

  In the present specification, examples of the therapeutic agent for multiple sclerosis include glatiramer acetate, interferon, baclofen, corticotropin, and mitoxantrone.

  In the present specification, the therapeutic agents for meningitis include, for example, ABLC, amphotericin B, cefozopran, cefpirome, fluconazole, haemophilus vaccine, meropenem (Meropenem), pneumococcal vaccine.

  In the present specification, examples of the therapeutic agent for Creutzfeld-Jakob disease include sodium pentosan polysulfate sodium.

  In the present specification, examples of the therapeutic agent for dementia (dementia) caused by AIDS encephalopathy include lexipafant, memantine hydrochloride, and CPI-1189.

  In the present specification, examples of the therapeutic agent for neurosis include TJ-15.

  In the present specification, the therapeutic agents for psychosomatic diseases include, for example, bromperidol, fltoprazepam, olanzapine, sultopride, sodium valproate (valproate semisodium), ziprasidone, Zuclopenthixol, zuclopenthixol acetate, zuclopenthixol decanoate, quetiapine fumarate fumarate, risperidone, prochlorpera maleate Examples include gin (prochlorperazine maleate) and aripiprazole.

  In this specification, as an anxiety treatment drug (anti-anxiety drug), for example, fltoprazepam (flutoprazepam), diazepam (diazepam), lorazepam (lorazepam), bromazepam (bromazepam), prazepam (prazepam), clothiazepam (clotiazepam), oxazepam (Oxazepam), fludiazepam (fludiazepam), medazepam (medazepam), chlordiazepoxide (chlordiazepoxide), alprazolam, etizolam, flutazolam (fulutazolam), mexazolam, cloxazolam (cloxazolam) Examples include dipotassium clorazepate, ethyl loflazepate, and tandospiron citrate.

  In the present specification, examples of therapeutic agents for schizophrenia include amisulpride, aripiprazole, clozapine, nemonapride, olanzapine, perospirone, quetiapine fumarate ( quetiapine fumarate), risperidone, talipexole, ziprasidone, zotepine, zuclopenthixol, zuclopenthixol acetate, zuclopenthixol acetate, decanoic acid Examples include sole (zuclopenthixol decanoate) and sertindole.

  In the present specification, for example, olanzapine, sodium valproate (valproate semisodium), quetiapine fumarate fumarate, risperidone, aripiprazole, ziprasidone, An example is lithium.

  In this specification, as a therapeutic agent (depressant) for depression, a tricyclic antidepressant, a tetracyclic antidepressant, a triazolopyridine antidepressant, a selective serotonin reuptake inhibitor (SSRI) And serotonin and noradrenaline reuptake inhibitors (SNRI) and the like. Specifically, for example, escitalopram oxalate oxalate, alprazolam, amisulpride, amoxapine, bupropion , Carbamazepine, citalopram hydrobromide, dihydroergocryptine, fluoxetine, fluvoxamine, lithium, lithium, mianserin, milnacipran, milnacipran (Minaprine), mirtazapine (mirtaza) pine), moclobemide, nefazodone hydrochloride, paroxetine, pirlindole, reboxetine, ST-200, sertraline, tianeptine, trazodone, trazodone Venlafaxine, fluoxetine + olanzapine (fluoxetine + olanzapine), olanzapine (olanzapine), lamotrigine, virucort, duloxetine hydrochloride, selegiline, gerone-ER (gerone) ER), imipramine hydrochloride, amitriptyline, trimipramine, clomipramine, nortriptyline, lofepramine, maprotiline maprotiline), setiptiline (setiptiline), dosulepin (dosulepin), it includes nomifensine (nomifensine) is.

  In the present specification, the therapeutic agents for epilepsy (antiepileptic drugs) include, for example, carbamazepine, chloral hydrate, clonazepam, diazepam, felbamate, phosphenytoin ( fosphenytoin, gabapentin, lamotrigine, levetiracetam, lorazepam, oxcarbazepine, phenobarbitone Na, phenobarbitone Na, tiagabine, topiramate, topiramate Sodium valproate (valproate semisodium), sodium valproate (valproate sodium), vigabatrin (vigabatrin), zonisamide (zonisamide), pregabalin (pregabalin), phenobarbital (phenobarbital), primidone (primidone), phenytoin (phe nytoin) and ethosuximide.

  In the present specification, examples of therapeutic agents for dystonia include AN-072, botulinum toxin.

  In the present specification, the therapeutic agent for diabetes includes, for example, haste, mixed, intermediate and / or continuous insulin preparations (for example, human insulin preparations synthesized by genetic engineering using Escherichia coli and yeast, bovine, Animal insulin preparations extracted from porcine pancreas), sulfonylureas (eg tolbutamide, chlorpropamide, glibenclamide, gliclazide, glimepiride, tolamide, tolazamide, aceto) Hexamide (acetohexamide), glyclopiramide, biguanide drugs (eg, phenformine, buformin hydrochloride, metformin hydrochloride), α-glucosidase inhibitors (eg, acarbose) (Acarbose), bo Ribose), insulin secretagogues (eg, nateglinide), insulin resistance improvers (eg, troglitazone, pioglitazone hydrochloride), GLP-1 receptor agonists, amylin agonists, Examples thereof include phosphotyrosine phosphatase inhibitors, dipeptidyl peptidase IV inhibitors, β3 adrenergic receptor agonists, gluconeogenesis inhibitors, and SGLT (sodium-glucose cotransporter) inhibitors.

  In this specification, as a therapeutic agent for diabetic complications, for example, aldose reductase inhibitors (for example, epalrestat, SNK-860, CT-112), neurotrophic factors (for example, NGF (Nerve Growth Factor: Nerve growth factor), NT-3, BDNF (Brain Derived Neurotrophic Factor)), nerve regeneration promoting agent, PKC inhibitor, AGE inhibitor, active oxygen scavenger, duloxetine hydrochloride and the like.

  In the present specification, as a therapeutic drug for hyperlipidemia, for example, statin HMG-CoA reductase inhibitors (for example, pravastatin sodium, atorvastatin calcium, simvastatin, lovastatin) (Lovastatin), rosuvastatin, cerivastatin, fluvastatin (fluvastatin, etc.), fibrate triglyceride lowering drugs (eg, clofibrate, bezafibrate, fenofibrate, simfibrate) , Clinofibrate, etc.), squalene synthase inhibitors, cholestyramin, nicotinic acid, probucol.

  In the present specification, as the central anticholinergic agent, for example, trihexyphenidyl hydrochloride, biperiden, piroheptine hydrochloride, mazaticol hydrochloride, metixene hydrochloride And profenamine.

  In the present specification, examples of the acetylcholinesterase inhibitor include donepezil hydrochloride, rivastigmine tartrate, galantamine, and zanapezil (TAK-147).

Herein, GABA _A receptor modulators as (e.g., GABA _A receptor agonists, etc.), for example, muscimol (muscimol), isoguvacine (Isoguvacine), clomethiazole, gaboxadol (4,5,6,7 Tetrahydroisoxazolo [5,4-c] pyridin-3-ol), ganaxolone (3α-hydroxy-3β-methyl-5α-pregnan-20-one), fengabine (2-[(butylimino)-(2-chlorophenyl) ) Methyl] -4-chlorophenol), 3-aminopropanesulfonic acid, 3- (aminomethyl) -5-methylhexanoic acid.

  In the present specification, examples of the adenosine A2A receptor blocker include istradefylline.

  In the present specification, β-amyloid protein production, secretion, accumulation, aggregation and / or deposition inhibitor includes, for example, β-secretase inhibitor, γ-secretase inhibitor, β-amyloid protein aggregation inhibitor, β-amyloid degrading enzyme, β amyloid vaccine and the like can be mentioned.

  In the present specification, examples of the apoptosis inhibitor include CPI-1189, IDN-6556, and CEP-1347.

  In this specification, examples of the neuronal differentiation and / or regeneration promoting agent include leteprinim potassium, xaliproden hydrochloride, and SB-216763.

  In this specification, examples of the neurotrophic factor include neurotrophin (eg, NGF (Nerve Growth Factor), BDNF (Brain Derived Neurotrophic Factor), NT-3, NT- 4/5, NT-6), TGF-β superfamily (eg, TGF-β1, TGF-β2, TGF-β3, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP) -7, BMP-8A, BMP-8B, BMP-14 (GDF-5), GDNF, neuroturin, artemin, persephin, GDF-1, GDF-8, GDF-15, inhibin α, inhibin β, DAF (dauer formation) 7) Neurokerine family (eg ciliary neurotrophic factor (CNTF), interleukin-6), increased Factors (e.g., IGF-1, b-FGF), or the like ABS-205 and the like.

  In this specification, as other brain function activator (for example, cerebral metabolism activator, cerebral circulation improver etc.), for example, nicergoline (nicergoline), ibudilast (ibudilast), aniracetam (aniracetam), ifenprodil (ifenprodil), Vinpocetine, idebenone, memantine hydrochloride, calcium hopantenate, amantadine hydrochloride, meclofenoxate hydrochloride, dihydroergotoxine mesylate, pyrithioxine hydrochloride, γ-aminobutyric acid, bifemelane hydrochloride, maleic acid lisuride , Indeloxazine hydrochloride, and propentofylline.

  In the present specification, examples of the diuretic include thiazide diuretics (for example, chlorothiazide, benzthiazide, hydrochlorothiazide, hydroflumethiazide, trichlormethiazide, trichlormethiazide, Cyclothiazide, metyclothiazide, polythiazide, quinethazone, metolazone, etc., loop diuretics (eg, furusemide, bumetanide, pumetanide, retanide, piletide) Etacrynic acid, etc.), potassium-sparing diuretics (eg, spironolactone, potassium canrenoate, amiloride, triamterene, etc.), xanthine derivatives ( In example, theobromine sodium salicylate, theobromine calcium salicylate), acetazolamide (acetazolamide), and the like.

  In this specification, as a beta receptor blocker, for example, propranolol (propranolol), alprenolol (alprenolol), pindolol (pindolol), timolol (timolol), carteolol (carteolol), nadolol (nadolol), nipradilol ( nipradilol), chilisolol (tilisolol), atenolol (acenolol), acebutolol (acebutolol), metoprolol (metprolol), bisoprolol (bisoprolol), betaxolol, labetalol (labetalol), arotinolol, lol .

  In the present specification, calcium channel blockers (calcium antagonists) include, for example, nifedipine, nicardipine, nitrendipine, nilvadipine, nisoldipine, manidipine, and benidipine (Benidipine), barnidipine, efonidipine, amlodipine, diltiazem, verapamil, clonidine hydrochloride.

  In this specification, as an angiotensin converting enzyme (ACE) inhibitor, for example, captopril (captopril), alacepril (lilaceopril), enalapril (enalapril), delapril (cilazapril), imidapril ( imidapril), perindopril, temocapril, and tandolapril.

  In the present specification, examples of the angiotensin II receptor antagonist include candesartan cilexetil, losartan, and valsartan.

  In the present specification, examples of the sodium channel blocker include ajmaline, procainamide hydrochloride, and riluzole.

  In the present specification, examples of the potassium channel opener include diazoxide, flupirtine, pinacidil, levcromacarim, rilmacalim, cromakalim, PCO-400, and SKP-450.

  In the present specification, examples of the antiplatelet drug include aspirin, ethyl icosapentaenoate, sodium ozagrel, beraprost sodium, alprostadil, ticlopidine hydrochloride hydrochloride), cilostazol, dipyridamole, sarpogrelate hydrochloride.

  In the present specification, examples of the anticoagulant include warfarin (for example, warfarin potassium), heparin (for example, heparin sodium, heparin calcium), antithrombin drug (for example, And antithrombin III, argatroban, hirudin).

  In the present specification, examples of thrombolytic agents include urokinase, nasalplase (nasaruplase, prourokinase), tissue plasminogen activator (t-PA), tisokinase, alteplase , Nateplase, monteplase, streptokinase, and pamiteplase.

  In the present specification, examples of the cyclooxygenase (COX) -2 inhibitor include celecoxib and rofecoxib.

  In the present specification, examples of the nonsteroidal anti-inflammatory drug include aspirin, mefenamic acid, diclofenac, fenbufen, indometacin, ibuprofen, ketoprofen ( Ketoprofen, naproxen, phenylbutazone, piroxicam, tenoxicam, meloxicam, celecoxib, and rofecoxib.

  In the present specification, examples of the steroid drug include methylprednisolone, triamcinolone, paramethasone, betamethasone, betamethasone, cortisone, hydrocortisone, hexestrol, cortisone acetate, Clobetasol propionate (trade name: delmobeto), clobetasone butyrate (trade name: kindabate), diflucortron valerate (trade name: texmetene, nerizona), dexamethasone (trade name: eulazone D, dexamethasone, decadarm), propionate butyrate Hydrocortisone acid (trade name: Pandel), Hydrocortisone butyrate (trade name: Plancol, Locoid), Prednisolone (trade name: Prednisolone, Bisio A), Betamethyrate Dzong (trade name: Tokudamu, Betonebeto, Rinderon V), mometasone furoate (trade name: Furumeta), and the like.

  In the present specification, examples of the antioxidant include linolenic acid, icosapentaenoic acid, docosahexaenoic acid, ascorbic acid, tocopherol acetate, and edaravone. Can be mentioned.

  In the present specification, examples of vitamins include ascorbic acid, tocopherol acetate, and mecobalamin.

  In this specification, examples of sex hormones or derivatives thereof include progesterone, estradiol, estradiol benzoate, and the like.

  In the present specification, examples of the glycerin preparation include glycerol.

  The above concomitant drugs are illustrative and are not limited thereto. In addition, the concomitant drugs include not only those found so far, but also those that will be found in the future based on the above-described mechanism. Furthermore, these drugs may be administered in combination of any two or more. (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof, or a prodrug thereof is used in combination with the above-mentioned drug, thereby preventing, treating and / or treating compared to the case where the drug is administered alone. Useful effects such as supplementing and / or enhancing the symptom progression inhibitory effect, reducing the dose and side effects of the drug, or preventing the development of drug resistance can be obtained.

[toxicity]
The toxicity of the drug of the present invention is sufficiently low and confirmed to be sufficiently safe for use as a pharmaceutical product. For example, in a single intravenous administration using a dog, (2R) -2-propyloctanoic acid was 100 mg / kg and no death was observed.

  The agent of the present invention is useful as a preventive, therapeutic and / or progress inhibitor for motor dysfunction. The motor dysfunction includes “peripheral nervous system diseases (for example, neuropathy, nerve dysfunction caused by compression of the caudad nerve due to spinal canal stenosis, cranial nerve palsy, diabetic peripheral neuropathy, myasthenia gravis, muscular dystrophy, etc.) Dysfunction ”,“ motor dysfunction caused by central nervous system diseases (eg, dystonia, Huntington's disease, spinal muscular atrophy, spinocerebellar degeneration, neurological dysfunction associated with spinal cord injury, disc herniation, etc.) ” Symptoms and signs of other motor dysfunctions that cannot be classified into (for example, peripheral neuropathic pain, dyskinesia, etc.).

Although the formulation example of the chemical | medical agent of this invention is disclosed below, this invention is not limited to these. Of course, various conditions may be changed without departing from the scope of the present invention.
Formulation Example 1
(2R) -2-Propyloctanoic acid (2.0 kg) and trisodium phosphate dodecahydrate (3.54 kg) were added to make 40 L using water for injection. After preparing a uniform solution, it is filtered through a sterile filter (Durapore 0.22 μm membrane), filled into plastic ampules in 2 mL portions, and autoclaved (123 ° C., 15 minutes) to give 100 mg of active ingredient in one ampule. 20,000 ampoules were obtained.
Formulation Example 2
Gelatin (15 kg) and concentrated glycerin (4.5 kg) were mixed at 70 ° C. in the presence of purified water (15 kg) to obtain a uniform solution. This solution and (2R) -2-propyloctanoic acid (0.6 kg) were put into a soft capsule filling machine (rotary soft capsule molding machine H-1 type; Kamata), and (2R) -2-propyloctanoic acid was added. A filled soft capsule live sphere was obtained. The obtained raw spheres were sequentially subjected to tumbler drying and shelf drying to obtain soft capsules (3000 capsules) containing 100 mg of (2R) -2-propyloctanoic acid in one capsule.

The agent comprising (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof or a prodrug thereof of the present invention is useful as a preventive, therapeutic and / or progression inhibitor for motor dysfunction. Therefore, it is useful as a medicine. The motor dysfunction includes “peripheral nervous system diseases (for example, neuropathy, nerve dysfunction caused by compression of the caudad nerve due to spinal canal stenosis, cranial nerve palsy, diabetic peripheral neuropathy, myasthenia gravis, muscular dystrophy, etc.) Dysfunction ”,“ motor dysfunction caused by central nervous system diseases (eg, dystonia, Huntington's disease, spinal muscular atrophy, spinocerebellar degeneration, neurological dysfunction associated with spinal cord injury, disc herniation, etc.) ” Symptoms and signs of other motor dysfunctions that cannot be classified into (for example, peripheral neuropathic pain, dyskinesia, etc.).

Claims (13)

  (2R) -2-Propyloctanoic acid, a salt thereof, a solvate thereof, or a prodrug thereof, a preventive, therapeutic and / or progress inhibitor for motor dysfunction.   The agent according to claim 1, wherein the motor dysfunction is a disorder caused by a peripheral nervous system disease.   Peripheral nervous system diseases are (1) peripheral nerve, cauda equina, nerve root and plexus disorders, (2) disorders of eye muscles, eye movements, regulation and refraction, (3) neurological dysfunction in inner ear diseases, (4) Neurological dysfunction associated with viral infections characterized by skin and mucosal lesions, (5) neurological dysfunction associated with protozoal diseases, (6) neurological dysfunction in diabetes, (7) neurological dysfunction in metabolic disorders, (8) Neural dysfunction in thyroid disorders, (9) Neural dysfunction due to malignant neoplasms of mesothelial and soft tissues, (10) Neural dysfunction due to malignant neoplasms of cranial nerves, (11) Benign neoplasms of peripheral nerves and autonomic nervous system (12) Neural dysfunction associated with head injury, (13) Neural dysfunction associated with neck injury, (14) Nervous dysfunction in spinal column injury, (15) Damage to trunk and extremities (16) Soft tissue disorders, (17) Inflammatory polyarthropathy, (18) Neurological disorders associated with trauma during childbirth, (19) Autonomic nervous system disorders, (20) Neuromuscular junction The agent according to claim 2, which is one or more diseases selected from (21) paralytic syndrome, (22) muscle disease and (23) systemic connective tissue disorder.   Peripheral nervous system disorders are mononeuropathy, polyneuropathy, hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease, Degelin-Sotta disease, inflammatory polyneuropathy, Guillain-Barre syndrome, trigeminal neuropathy, glossopharyngeal neuropathy , Facial neuropathy, painful tics, postherpetic neuralgia, neuropathic muscular atrophy, phantom limb pain, acute brachial neuritis, acute brachial plexitis, brachial plexus disorder, thoracic outlet compression syndrome, nerve roots due to disc herniation Dysfunction due to compression of the plexus and nerve plexus, nerve dysfunction due to compression of the caudad nerve due to spinal canal stenosis, cranial nerve palsy, diabetic peripheral neuropathic pain, neurological dysfunction associated with spinal cord injury, sciatica, birth Injury, hereditary sensory autonomic neuropathy, myasthenia gravis, neonatal myasthenia gravis, congenital myasthenia gravis Group, eye muscle myasthenia gravis, toxic neuromuscular transmission disorder due to drugs or toxins, Eaton-Lambert syndrome, generalized tonic syndrome, motor paralysis, muscular dystrophy, channelopathy, myopathy, multisystem encephalomyopathy, progressive extraocular muscles The agent according to claim 2, wherein the agent is one or more diseases selected from paralysis, Kearns-Seyre syndrome, mitochondrial encephalomyopathy, dermatomyositis and polymyositis.   The agent according to claim 1, wherein the motor dysfunction is a disorder caused by a central nervous system disease.   Central nervous system diseases are (1) extrapyramidal disorders and abnormal movement, (2) system atrophy, (3) neurodegenerative diseases, (4) demyelinating diseases, (5) interstitial and seizure disorders, ( 6) cerebral palsy, (7) neurological dysfunction due to inflammatory diseases of the central nervous system, (8) neurological dysfunction due to viral infection of the central nervous system, (9) central nervous system characterized by skin and mucosal lesions Neurological dysfunction due to viral infection, (10) neurological dysfunction due to tuberculosis, (11) neurological dysfunction due to infection that takes sexual transmission mode, (12) neurological dysfunction due to protozoal diseases of the central nervous system, Neurological dysfunction in nutritional deficiencies, (14) neurological dysfunction due to malignant neoplasms or secondary malignant neoplasms of the brain and central nervous system, (15) neurological dysfunction due to benign neoplasms of the central nervous system, (16) cerebrovascular Nervous machine with disease Disorders, (17) central nervous system neurological dysfunction associated with head injury, (18) central nervous system neurological dysfunction in spinal column disorders, (19) neurological dysfunction associated with pregnancy-related central nervous system maternal disorders , (20) neurological dysfunction of the central nervous system due to trauma during childbirth, (21) neurological dysfunction caused by drug, drug and biological product poisoning and / or its sequelae and (22) medicinal use 6. The agent according to claim 5, wherein the agent is one or more diseases selected from the toxic effects of non-performing substances and / or neurological dysfunctions caused by the subsequent and sequelae thereof.   Central nervous system disorders are dystonia, abnormal movement, periodic limb movement disorder, restless leg syndrome, myoclonus, chorea-ataxia, tic, athetosis, choreoathetosis, hemiparism, Huntington's disease, hereditary ataxia, spinal cord Muscular atrophy, motor neuron disease, primary lateral sclerosis, progressive bulbar paralysis, progressive pseudobulbar paralysis, paraneoplastic syndrome, spinocerebellar degeneration, Friedreich ataxia, multiple system atrophy, Card Joseph's disease, Shy Dräger syndrome, late cerebellar cortical atrophy, dentate nucleus red nucleus pallidal atrophy, Tay-Sachs disease, subacute association spinal degeneration, leukodystrophy, spastic cerebral palsy, Due to paralytic or non-paralytic acute gray leukomyelitis, subacute sclerosing panencephalitis, neurological dysfunction due to Coxsackie virus infection, enterovirus infection Neurological dysfunction, neurological dysfunction due to compression of cauda equina by spinal stenosis, agent according to claim 5, wherein the one or more diseases selected from neurological dysfunction and herniated disc with spinal cord injury.   Motor dysfunction (1) Numbness, pain and neuropathic pain, (2) Symptoms and signs related to nervous and musculoskeletal systems, (3) Symptoms and signs related to skin and subcutaneous tissue, (4) Symptoms related to speech and speech And one or more diseases selected from (5) symptoms and signs related to cognition, perception, emotional state and behavior, and (6) behavioral and emotional disorders that develop in childhood, childhood and adolescence Item 1. The agent according to Item 1.   Motor dysfunction is acute postoperative pain, postoperative pain syndrome, chronic intractable pain, peripheral neuropathic pain, cancer pain, neuropathic pain syndrome, painful traumatic mononeuropathy, painful polyneuropathy, diabetes One or more diseases selected from peripheral peripheral neuropathic pain, central pain syndrome, complex local pain syndrome, reflex sympathetic dystrophy, burning pain, phantom limb pain, abnormal involuntary movement, dyskinesia, and ataxia 1. The agent according to 1.   2. The oral dosage form according to claim 1, wherein the dose of (2R) -2-propyloctanoic acid, its salt, its solvate or their prodrug per administration is about 50 mg to about 1500 mg. Agent.   The agent according to claim 10, wherein (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof or a prodrug thereof is administered for 1 day to about 1 year.   Intravenous administration, wherein the dose of (2R) -2-propyloctanoic acid, its salt, its solvate or their prodrug per administration is about 0.5 mg to about 25 mg per kg body weight The agent according to claim 1 for use. The agent according to claim 12, wherein the administration period of (2R) -2-propyloctanoic acid, a salt thereof, a solvate thereof or a prodrug thereof is 1 day to about 10 days.