JP2011051942A - Therapeutic agent for dementia - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a therapeutic agent for dementia having excellent improving and treating effect on dementia and/or accessory symptoms accompanying it and effective for cases which are hardly improved by generally used treatment methods. <P>SOLUTION: The therapeutic agent for dementia is obtained by combining ferulic acid or its pharmaceutically acceptable salt with Ashwagandha or its extract. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a therapeutic agent for dementia for improving and treating dementia and / or various accompanying symptoms associated therewith. More specifically, cognitive dysfunction and / or associated delirium, hallucinations and delusions associated with dementia, including a number of higher cortical dysfunctions including memory, thought, orientation, understanding, learning ability, language, judgment, etc. The present invention relates to a dementia drug for improving and treating various psychological and neurological symptoms such as depression, motivation, sleep disorder, anxiety, irritability, tension, general malaise, indefinite complaints, Parkinson's symptoms, and nerve paralysis.

  Dementia is a disease characterized by cognitive dysfunction, mainly memory, judgment, and disorientation, such as “Alzheimer's dementia”, “vascular dementia”, “brain injury, brain dysfunction and physical disease” There are many subdivisions such as “Other mental disorders”. The first occurrence of this disease generally occurs in the 60s to 80s or later. Many follow a progressive course, while various psychic gods such as delirium, hallucinations and delusions, depressed mood, decreased motivation, sleep disorders, anxiety, irritability, tension, general malaise, indefinite complaints, Parkinson's symptoms, and nerve paralysis Symptoms and neurological symptoms are present.

  As a general treatment for dementia, there is pharmacotherapy using a cholinesterase inhibitor in Alzheimer type dementia. In the case of vascular dementia, prevention of progression is important, and drugs such as antihypertensive drugs, anticoagulants, and antiplatelet drugs may be used. In addition, antipsychotic drugs, antidepressants, benzodiazepines, anti-Parkinson drugs and the like can be prescribed for various symptoms such as the above-mentioned psychological symptoms and neurological symptoms associated with dementia. Yokukansan is also often used to treat dementia.

  However, the use of cholinesterase inhibitors is limited due to side effects such as gastrointestinal symptoms and liver toxicity. In addition, although antihypertensive drugs, anticoagulants, antiplatelet drugs and the like have a preventive effect, it is generally difficult to expect an improvement effect for dementia itself. Yokukansan is known to cause hypokalemia and should be used with caution. In addition, it should be noted that drugs such as antipsychotics, antidepressants, benzodiazepines and antiparkinsonian drugs can cause excitement, confusion, hypersedation, etc. when used in the elderly.

  In recent years, a wide variety of people with dementia such as “Alzheimer-type dementia”, “vascular dementia”, and “other mental disorders due to brain damage, brain dysfunction, and physical disorders” and Lewy small Research results that activated microglia (active microglia) are increasing in the brain of somatic patients and that these are involved in the pathogenesis of dementia have been reported (Non-Patent Document 1, And 2). Research results suggesting that active microglia are also involved in the pathogenesis of patients with schizophrenia, Parkinson's disease, Pick's disease, etc. whose main symptoms are depression and hallucinatory delusions (non-patented) References 3, 4, and 5).

  On the other hand, recently, scientists are attracting attention that substances contained in various foods and plants have an action of improving brain function (Non-patent Document 6). Among them, ferulic acid, which is contained in various foods and has strong antioxidant and anti-inflammatory effects, has been studied by animal experiments to suppress the activation of microglia and to have a neuroprotective effect. (Non-Patent Documents 7, 8, and 9). In addition, the witanoside contained in Ashwagandha (Withania somnifera Dunal), which is used as an anti-dementia drug in Indian traditional medicine, also has a nerve regeneration action, a synapse regeneration action, and a cognitive function improvement action through animal experiments. The research result was reported (Non-patent document 10 and Patent document 1).

JP 2006-176428 A

Gerhard A, Schwarz J, Myers R, Wise R, Banati RB. Evolution of microglial activation in patients after ischemic stroke: a [11C] (R) -PK11195 PET study. Neuroimage 24 (2): 591-595, 2005 Mrak RE, Griffin WS. Common inflammatory mechanisms in Lewy body disease and Alzheimer disease. J Neuropathol Exp Neurol 66: 683-686, 2007. McNally L, Bhagwagar Z, Hannestad J. Inflammation, glutamate, and glia in depression: a literature review.CNS Spectr 13: 501-510, 2008. van Berckel BN, Bossong MG, Boellaard R, Kloet R, Schuitemaker A, Caspers E, Luurtsema G, Windhorst AD, Cahn W, Lammertsma AA, Kahn RS.Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C ] PK11195 positron emission tomography study. Biol Psychiatry 64: 820-822, 2008. Ouchi Y, Yoshikawa E, Sekine Y, Futatsubashi M, Kanno T, Ogusu T, Torizuka T. Microglial activation and dopamine terminal loss in early Parkinson's disease. Ann Neurol. 57: 168-175, 2005. Gomez-Pinilla F. Brain foods: the effects of nutrients on brain function.Nat Rev Neurosci 9: 568-578, 2008. Wenk GL, McGann-Gramling K, Hauss-Wegrzyniak B, Ronchetti D, Maucci R, Rosi S, Gasparini L, Ongini E. Attenuation of chronic neuroinflammation by a nitric oxide-releasing derivative of the antioxidant ferulic acid.J Neurochem 89: 484 -493, 2004. Cho JY, Kim HS, Kim DH, Yan JJ, Suh HW, Song DK.Inhibitory effects of long-term administration of ferulic acid on astrocyte activation induced by intracerebroventricular injection of beta-amyloid peptide (1-42) in mice.Prog Neuropsychopharmacol Biol Psychiatry. 29: 901-907, 2005. Cheng CY, Su SY, Tang NY, Ho TY, Chiang SY, Hsieh CL. Ferulic acid provides neuroprotection against oxidative stress-related apoptosis after cerebral ischemia / reperfusion injury by inhibiting ICAM-1 mRNA expression in rats.Brain Res 1209: 136- 150, 2008. Kuboyama T, Tohda C, Komatsu K. Withanoside IV and its active metabolite, sominone, attenuate Aβ (25-35) -induced neurodegeneration. Eur J Neurosci 23: 1417-26, 2006.

  However, there has been no report that ferulic acid or withanoside has confirmed the therapeutic effect of dementia on humans. Further, according to the experience of the present inventor, even when one of these is used, the effect of treating dementia is not always sufficient, and there are not a few cases that are difficult to improve even by these treatment methods.

  Therefore, the present invention provides a therapeutic agent for dementia that is excellent in improvement / treatment effects on dementia and / or accompanying symptoms accompanying it, and that is effective even for patients who are difficult to improve by commonly used treatments. For the purpose.

  The present inventors combined ferulic acid and ashwagandha and combined their different effects to effectively improve dementia and / or various accompanying symptoms that are difficult to improve by commonly used treatments. I hypothesized that it might be. And the composition which combined ferulic acid and Ashwagandha extract was actually administered with respect to the dementia patient, the effect was confirmed, and this invention was completed.

  The present invention provides a therapeutic agent for dementia comprising a combination of ferulic acid or a pharmaceutically acceptable salt thereof and Ashwagandha or an extract thereof.

  The therapeutic agent for dementia of the present invention has an excellent therapeutic effect on dementia and / or various accompanying symptoms accompanying the symptoms that are difficult to be improved by a commonly used treatment method.

  The ferulic acid used by this invention can also be extracted from the plant containing this, and can also be manufactured industrially by chemical synthesis.

  As the plant containing ferulic acid, for example, coffee, onion, Japanese radish, lemon, senkyu, touki, pine, auren, agi, sweet potato, corn, barley, wheat, rice and the like are preferable, and rice is particularly preferable. For example, waste oil when producing rice oil from rice bran, waste oil, which is a by-product, alkaline oil cake, and crude fatty acid are used as raw materials, and these can be obtained by alkaline hydrolysis at low cost.

  Ferulic acid can also be produced, for example, by condensation decarboxylation of 4-hydroxy-3-methoxybenzaldehyde (vanillin) and malonic acid.

  Ferulic acid can be used in the form of a pharmaceutically acceptable salt to improve water solubility and increase effectiveness. Examples of such a salt-forming base substance include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide; alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide; Inorganic bases such as ammonium hydroxide; basic amino acids such as arginine, lysine, histidine, ornithine; organic bases such as monoethanolamine, diethanolamine, and triethanolamine can be used, particularly alkali metal hydroxides and alkaline earths A metal hydroxide is preferred.

  In addition, Ashwagandha (Withania somnifera Dunal) used in the present invention is an evergreen shrub plant of the solanaceous family along the coasts of India, Nepal, the Middle East, and the Mediterranean, and is widely distributed in the tropics centering on India. Ashwagandha has long been used for health promotion in the traditional Indian medicine “Ayurveda”.

  In the present invention, Ashwagandha mainly uses rhizome parts or leaves. Ashwagandha may be used as a dry pulverized product of rhizomes or leaves, but is preferably used as an extract. Although it does not specifically limit as an extract, Preferably it is an ethanol aqueous solution extract. Ashwagandha extract is sold, for example, as an extract dry powder from Maechu Co., Ltd., Nippon Shinyaku Co., Ltd., and the like.

  The therapeutic agent for dementia of the present invention may be in the form of a combination containing ferulic acid or a pharmaceutically acceptable salt thereof and Ashwagandha or an extract thereof, and ferulic acid or a pharmaceutically acceptable salt thereof. It may be in the form of a kit comprising a preparation containing an acceptable salt and a preparation containing Ashwagandha or an extract thereof.

  Even if the therapeutic agent for dementia of the present invention is in any of the above forms, each preparation can be produced using an acceptable carrier. In producing the therapeutic agent for dementia of the present invention, the active ingredients, that is, ferulic acid or a pharmaceutically acceptable salt thereof, and Ashwagandha or an extract thereof are usually mixed using an excipient or added. It is diluted with a form or encapsulated in a carrier that can be in the form of a capsule, sachet, paper or other container. When an excipient is used as a diluent, the excipient may be a solid, semi-solid, liquid composition that acts as a medium, carrier or medium for the active ingredient. Thus, the therapeutic agents for dementia of the present invention include tablets, pills, powders, troches, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, soft and hard gelatin capsules. It can be in the form of suppositories, suppositories, sterile injectable solutions and sterile packaged powders. Moreover, it can also be set as foodstuffs, such as confectionery, such as a candy, gum | gum, and a cookie, and a drink, bread, and soup. The therapeutic agent for dementia of the present invention may be for oral use or for injection, but is preferably for oral use.

  In the case of a kit comprising a preparation containing ferulic acid or a pharmaceutically acceptable salt thereof and a preparation containing Ashwagandha or an extract thereof, both forms may be the same or different. Good. For example, one preparation may be for oral use and the other preparation may be an injection. Preferably, both are oral forms.

  In the present invention, ferulic acid or a salt thereof, Ashwagandha or an extract thereof is administered to each dementia patient in an effective amount, thereby causing various symptoms associated with dementia, such as memory, thinking, orientation, understanding, learning ability, Cognitive dysfunction and / or associated delirium, hallucinations and delusions, depression, motivation, sleep disorders, anxiety, agitation, tension, general malaise, indefinite complaints Various psychiatric symptoms and neurological symptoms such as Parkinson's symptoms and nerve palsy can be improved. It is also effective for patients who are difficult to improve with conventional treatments for dementia.

  The effective amount means a therapeutically effective amount. The specific dosage of the therapeutic agent for dementia of the present invention can be appropriately determined in consideration of the symptoms, age, body weight, etc. of individual patients, dosage form, number of administrations, combined use of other agents, etc. In the case of administration, the dosage per day for an adult is preferably 50 to 1000 mg / day, more preferably 100 to 600 mg / day, particularly 200 to 400 mg / day for ferulic acid or a salt thereof, and Ashwagandha or an extract thereof is The extract dry powder is preferably 50 to 1000 mg / day, more preferably 100 to 600 mg / day, and particularly preferably 200 to 400 mg / day.

  The following examples further illustrate the present invention in detail but are not intended to limit the scope of the invention in any way.

Example 1
A 72-year-old woman gradually became impaired in short-term memory, such as forgetting to be instructed by her family and forgetting to prepare meals, and became impaired in daily life. In addition, delusions such as “use savings” have emerged, and the anger of getting angry with trivial things has also been exhibited. For this reason, medical care began. MMSE (Folstein MF et al. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 12: 189-98, 1975) was 19 points. MRI showed mild temporal lobe atrophy and ventricular enlargement, but there were no findings of cerebral organ disease such as a history of cerebral infarction, in addition to findings of age-appropriate lacunar infarct under the cerebral cortex. From these findings, Alzheimer's dementia was diagnosed by ICD-10 and DSM-IV.

  As drug therapy, cholinesterase inhibitor donepezil 3 mg / day was started, but side effects of nausea and bradycardia appeared, and it was difficult to continue the drug. For delusions and irritability, benzodiazepine anxiolytics and small amounts of antipsychotics were used, but side effects such as staggering and somnolence, or extrapyramidal symptoms such as dysphagia, ticking, It was difficult to continue taking any drug.

  Therefore, the policy was to use ferulic acid, starting from 200 mg / day (100 mg in the morning, 100 mg in the evening), and maintaining the internal dose. Four weeks later, the patient's delusions improved significantly. In addition, the behavior became calm and angry. No side effects were observed. However, short-term memory impairment continued. The MMSE at this point was 18 points.

  He continued taking ferulic acid for 6 months, but his short-term memory impairment did not improve, and his MMSE scored 18 points. Therefore, in addition to ferulic acid 200 mg / day (100 mg in the morning, 100 mg in the evening), Ashwagandha extract 200 mg / day (100 mg in the morning and 100 mg in the evening) was used in combination.

  Since the beginning of 3 months, MMSE scored 18 points, but it became possible to take regular medication on its own, which was impossible before. In addition, since 6 months have passed since the combination therapy with ferulic acid and Ashwagandha extract was started, the amount of conversation increased and the activity increased, including a spontaneous walk. These have reduced the burden on family care and improved the quality of life. For this reason, ferulic acid was discontinued and treatment with Ashwagandha extract alone was selected.

  However, since one month has passed since the use of ferulic acid was stopped, delusions and anger began to appear again. Therefore, the treatment policy was changed again, and combination therapy with ferulic acid 200 mg / day (100 mg in the morning, 100 mg in the evening) and Ashwaganda extract Ashwagandha extract 200 mg / day (100 mg in the morning, 100 mg in the evening) was started. Later, delusions and anger improved.

  After that, the combination therapy with ferulic acid 200mg / day (100mg in the morning, 100mg in the evening) and Ashwaganda extract Ashwaganda extract 200mg / day (100mg in the morning, 100mg in the evening) has been maintained for 1 year, but MMSE has 20 points. The disorder of memorization improved slightly, and there was no recurrence of symptoms such as delusions and anger.

Example 2
A 78-year-old man often has short-term memory problems such as repeating the same questions many times, and a delirium state in which disorientation such as lack of date sensation is observed in addition to hyperactivity. became. In addition, emotions became unstable, such as sudden crying or anger without incentives. Walking became small, and Parkinson's symptoms such as finger tremor and mask-like face began to appear, resulting in obstacles to daily life. For this reason, medical care began. MMSE scored 18 points. On a MRI, age-appropriate atrophy was observed. A large number of lacunar infarcts were observed under the basal ganglia and cerebral cortex centering on the striatum. From these findings, vascular dementia was diagnosed by ICD-10 and DSM-IV.

  Amantadine, an antiparkinsonian drug, was used as a pharmacotherapy, but emotions became unstable and it was difficult to continue to use. For unstable emotions, benzodiazepine anxiolytics and small amounts of antipsychotics were used, but side effects such as wandering and somnolence, or extrapyramidal symptoms such as dysphagia and small gait appeared, and Parkinson Symptoms worsened, and it was difficult to continue taking any drug. Disorientation also worsened.

  Therefore, the policy was to use ferulic acid, starting from 200 mg / day (100 mg in the morning, 100 mg in the evening), and maintaining the internal dose. Four weeks later, the patient's speech was calm and emotion was stable. Disorientation also improved and awareness became clearer. No side effects were observed. However, short-term memory impairment continued. The MMSE at this point was 17 points.

  He continued taking ferulic acid for 6 months, but his short-term memory impairment did not improve, and his MMSE scored 17 points. Therefore, in addition to ferulic acid 200 mg / day (100 mg in the morning, 100 mg in the evening), Ashwagandha extract 200 mg / day (100 mg in the morning and 100 mg in the evening) was used in combination.

  Since then, 3 months have passed, and although MMSE has been 17 points, it has become possible to take regular medication on its own, which was previously impossible. In addition, since 6 months have passed since the combination therapy with ferulic acid and Ashwagandha extract was started, the activity increased, Parkinson's symptoms such as small walks also improved, and it became possible to go out spontaneously. . For this reason, ferulic acid was discontinued and switched to treatment with Ashwagandha extract alone.

  However, since one month has passed since the use of ferulic acid was stopped, emotions became unstable again and emotional incontinence was recognized. Delirium was also exhibited. Parkinson's symptoms have again been observed.

  For this reason, the treatment policy was changed again, and combination therapy with ferulic acid 200 mg / day (100 mg in the morning, 100 mg in the evening) and Ashwaganda extract Ashwaganda extract 200 mg / day (100 mg in the morning, 100 mg in the evening) was started. After that, emotions stabilized and Parkinson's symptoms improved.

  After that, the combination therapy with ferulic acid 200mg / day (100mg in the morning, 100mg in the evening) and Ashwaganda extract Ashwaganda extract 200mg / day (100mg in the morning, 100mg in the evening) was maintained for 1 year, but MMSE was 17 points. There was no exacerbation of memorization disorder, unstable emotions, disorientation, and Parkinson's symptoms improved and continued to be in good condition.

Example 3
A 64-year-old woman had subarachnoid hemorrhage at age 61 and underwent brain surgery. Despite his life, the disturbance of consciousness continued for several weeks. After that, although the consciousness was recovered, the aftereffects such as talking about unknown meanings and presenting the dynamism were left. The MMSE scored 12 points.

  Because of repeated delirium with confusion and often excitement, treatment with antipsychotic drugs was started. In addition, depression occurred at the age of 63, and treatment with antidepressants was started. However, the combination of antidepressants made emotions unstable and suddenly started crying or getting excited. For this reason, antidepressants could not be used. On the other hand, although the delirium state was improved by antipsychotic drugs, Parkinson's symptoms were observed, such as a decrease in the number of mouths, a hard expression, and the appearance of small gait. As a result, there was a strong hope from the family that no treatment with antipsychotics should be given.

  For this reason, the treatment policy was to use ferulic acid and to gradually reduce the antipsychotic drugs. Ferulic acid was started at 200 mg / day (100 mg in the morning, 100 mg in the evening), and the dose was maintained. Thereafter, over 4 weeks, antipsychotic drugs were gradually withdrawn. Despite discontinuation of the antipsychotic drug, the patient's behavior became mild and emotions stabilized. Disorientation also improved and awareness became clearer. In addition, it has become possible to respond to other people's voices with a smile. Delirium is no longer triggered. No side effects were observed. However, short-term memory impairment continued. The MMSE at this time was 13 points.

  He continued taking ferulic acid for 6 months, but his short-term memory impairment did not improve, and his MMSE scored 12 points. Therefore, in addition to ferulic acid 200 mg / day (100 mg in the morning, 100 mg in the evening), Ashwagandha extract 200 mg / day (100 mg in the morning and 100 mg in the evening) was used in combination.

  Since then, since 3 months have passed, the MMSE scored 13 points, but the activity increased and the frequency of smiles increased. In addition, since 6 months have passed since the combination therapy with ferulic acid and Ashwagandha extract was started, it became possible to walk smoothly. For this reason, ferulic acid was discontinued and switched to treatment with Ashwagandha extract alone.

  However, since one month has passed since the use of ferulic acid was stopped, emotions became unstable again, and delirium was recognized.

  Therefore, the treatment policy was changed again, and combination therapy with ferulic acid 200 mg / day (100 mg in the morning, 100 mg in the evening) and Ashwaganda extract Ashwagandha extract 200 mg / day (100 mg in the morning, 100 mg in the evening) was started. Later, emotions stabilized and delirium improved.

  After that, the combination therapy with ferulic acid 200mg / day (100mg in the morning, 100mg in the evening) and Ashwaganda extract Ashwaganda extract 200mg / day (100mg in the morning, 100mg in the evening) was maintained for 1 year, but MMSE was 16 points. Although there is no marked improvement in the ability to remember, unstable emotion, disorientation, and Parkinson's symptoms are not observed, and the condition continues.

Example 4
A 75-year-old woman began to have the vision that her grandson had been playing at the desk for about a year. In addition, from the half year ago, the posture of leaning forward has increased, and Parkinson's symptoms such as small gait and finger tremor have appeared. Short-term memory impairment was also observed, with an MMSE of 22 points. In addition, the delirium state accompanied by the excitement state appeared repeatedly. MRI examination showed no abnormality, but cerebral blood flow SPECT examination showed decreased blood flow from the parietal lobe to the temporal and occipital lobes. From these, Lewy body disease was diagnosed.

  For this reason, treatment with donepezil and anxiolytics was started. However, donepezil was difficult to use because it induced bradycardia. Also, the use of anti-anxiety drugs was not possible due to the appearance of wandering and often falling. Therefore, we decided to use Yokukansan, which is effective for this disease. However, hypokalemia occurred and the drug was discontinued.

  For this reason, the policy was to use ferulic acid. Ferulic acid was started at 200 mg / day (100 mg in the morning, 100 mg in the evening), and the dose was maintained. Four weeks later, the patient's hallucinations disappeared and no delirium occurred. Parkinson's symptoms also improved, and the symptoms such as stretching back and finger tremor disappeared. Consciousness became clear and I was able to have a peaceful conversation with my family. No side effects were observed. However, short-term memory impairment continued. The MMSE at this point was 21 points.

  He continued taking ferulic acid for 6 months, but his short-term memory impairment did not improve and his MMSE remained at 21 points. Therefore, in addition to ferulic acid 200 mg / day (100 mg in the morning, 100 mg in the evening), Ashwagandha extract 200 mg / day (100 mg in the morning and 100 mg in the evening) was used in combination.

  Since then, since 3 months have passed, although the MMSE scored 22 points, the activity increased further and the frequency of smiles increased. In addition, since 6 months have passed since the combination therapy with ferulic acid and Ashwagandha extract was started, walking became smooth and Parkinson's symptoms improved. For this reason, ferulic acid was discontinued and switched to treatment with Ashwagandha extract alone.

  However, from the time when the use of ferulic acid was stopped and one month passed, it became hallucinations again, and delirium often appeared. Parkinson's symptoms such as finger tremors and masked facial features have been observed.

  Therefore, the treatment policy was changed again, and combination therapy with ferulic acid 200 mg / day (100 mg in the morning, 100 mg in the evening) and Ashwaganda extract Ashwagandha extract 200 mg / day (100 mg in the morning, 100 mg in the evening) was started. Later, emotions stabilized and delirium improved.

  After that, the combination therapy with ferulic acid 200mg / day (100mg in the morning, 100mg in the evening) and Ashwaganda extract Ashwaganda extract 200mg / day (100mg in the morning, 100mg in the evening) was maintained for 1 year, but MMSE was 23 points. Although there is no marked improvement in memorization, no vision, disorientation, delirium, or Parkinson's symptoms have been observed, and the patient continues to be in good condition.

Example 5
The 58-year-old man was originally a serious and serious personality. However, from about a year ago, actions that were not seen before, such as making fun of others and laughing or making obscene talks public, have been recognized. Also, in addition to disapproval of misuse, such as using spoons and knives incorrectly, there was also a problem with the ability to remember. In addition, it is now possible to accept a lingering language that repeats a ridiculous response to any question. The anger was also increased. MRI showed atrophy in the frontal and temporal lobes. From these, it was diagnosed as Pick's disease. MMSE scored 24 points. We decided to use ferulic acid for treatment.

  Ferulic acid was started at 200 mg / day (100 mg in the morning, 100 mg in the evening), and the dose was maintained. Six weeks later, ghosts and obscene remarks began to decline. Disapproval and revocation also improved. However, short-term memory impairment continued, with a MMSE of 25 at this point.

  He continued taking ferulic acid for 6 months, but his short-term memory impairment did not improve and his MMSE remained at 25. Therefore, in addition to ferulic acid 200 mg / day (100 mg in the morning, 100 mg in the evening), Ashwagandha extract 200 mg / day (100 mg in the morning and 100 mg in the evening) was used in combination.

  Since then, since 3 months have passed, although the MMSE has not changed at 25 points, the changed personality has almost returned. In addition, it became possible to work from about six months after the start of combination therapy with ferulic acid and Ashwagandha extract. For this reason, ferulic acid was discontinued and switched to treatment with Ashwagandha extract alone.

  However, since one month has passed since the use of ferulic acid was stopped, personality changes such as increased anger, foolishness, and playfulness have been recognized.

  Therefore, the treatment policy was changed again, and combination therapy with ferulic acid 200 mg / day (100 mg in the morning, 100 mg in the evening) and Ashwaganda extract Ashwagandha extract 200 mg / day (100 mg in the morning, 100 mg in the evening) was started. After that, her symptoms improved again and she continued working.

  Maintained the combination therapy with ferulic acid 200mg / day (100mg in the morning, 100mg in the evening) and Ashwaganda extract Ashwagandha extract 200mg / day (100mg in the morning, 100mg in the evening). One year has passed, but the MMSE scored 27 points. Although no significant improvement in force disorder has been observed, symptoms such as personality changes have improved and continue to be in good condition.

Claims (4)

  A therapeutic agent for dementia comprising a combination of ferulic acid or a pharmaceutically acceptable salt thereof and Ashwagandha or an extract thereof.   The therapeutic agent for dementia according to claim 1, which is a combination drug containing ferulic acid or a pharmaceutically acceptable salt thereof and Ashwagandha or an extract thereof.   The therapeutic agent for dementia according to claim 1, which is a kit comprising a preparation containing ferulic acid or a pharmaceutically acceptable salt thereof and a preparation containing Ashwagandha or an extract thereof.   It is an oral formulation, The dementia therapeutic agent in any one of Claims 1-3.