Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/13—Amines
  • A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Definitions

• the present invention relates to a therapeutic or preventive agent for dementia and behavioral psychological symptoms.
• Dementia is so-called dementia, and is a condition / symptom that interferes with social life and occupational functions due to cognitive impairment.
• cognitive impairment is a concept that collectively refers to intellectual functions such as learning, viewing, listening, speaking, and thinking.
• the symptoms of dementia are generally classified into two types: core symptoms commonly seen in people with dementia and peripheral symptoms that are thought to appear due to various factors.
• Core symptoms include disorientation, poor memory, poor understanding and judgment, memory loss, aphasia (language impairment), apraxia (exercises motor activity despite normal motor function) Symptom such as disability (unable to cognitively identify an object despite normal sensory function), executive dysfunction (cannot plan and execute it).
• Peripheral symptoms include behavioral disorders such as hallucinations, delusions, excitement, derepression, filthy behavior, habits, resistance to care, and sleep disorders. These symptoms are behavioral psychological symptoms (BPSD (Behavioral and Psychological Symptoms of Dementia)).
• BPSD Behavioral and Psychological Symptoms of Dementia
• Core symptoms are important symptoms of dementia, but caregiving family members and facility staff are difficult to deal with and suffer from peripheral symptoms such as late-night snoring rather than core symptoms.
• Non-patent Documents 1 and 2 Conventionally, as a treatment for behavioral psychological symptoms of dementia, administration of an antipsychotic drug (risperidone) (Non-patent Documents 1 and 2) and administration of Yokukansan (Non-patent Document 3) have been reported.
• risperidone an antipsychotic drug
• Yokukansan administration of Yokukansan
• the nighttime behavioral disorder is considered to be caused by a decrease in melatonin, and the melatonin agonist (S) -N- [2- (1,6,7,8-tetrahydro-2H-indeno
• S melatonin agonist
• Patent Document 1 a technique for suppressing behavioral disturbance at night using [5,4-b] furan-8-yl) ethyl] propionamide
• fluvoxamine is known as a selective serotonin reuptake inhibitor (SSRI) and widely known as an antidepressant treatment.
• SSRI selective serotonin reuptake inhibitor
• fluvoxamine is also used as a treatment for anxiety disorder, obsessive compulsive disorder, eating disorder, attention deficit / hyperactivity disorder, premenstrual syndrome and the like.
• Non-Patent Documents 1 and 2 As pointed out in Non-Patent Documents 4 and 5, accompanying aspiration, falls, oversedation, cognitive decline, myocardial infarction, etc. Symptoms (side effects) often occur, and its safety is a problem.
• Non-Patent Document 6 In addition, in the case of administration of yokukansan described in Non-Patent Document 3, it is pointed out in Non-Patent Document 6 that pseudoaldosteronism may appear by long-term administration.
• Patent Document 3 The technique described in Patent Document 3 is applied to nighttime behavioral disorder among peripheral symptoms, and an effective drug is desired for other peripheral symptoms.
• the present invention does not cause concomitant symptoms (side effects) such as aspiration, falls, oversedation, cognitive decline, myocardial infarction, etc., and behavioral psychological symptoms that do not cause pseudoaldosteronism even after long-term administration. It aims at providing the treatment or prevention agent of the dementia which accompanies it.
• the invention according to claim 1 is a therapeutic or prophylactic agent for dementia comprising fluvoxamine or a pharmaceutically acceptable fluvoxamine salt as an active ingredient.
• the invention according to claim 2 is a therapeutic or preventive agent for dementia accompanied by an active ingredient and behavioral psychological symptoms of fluvoxamine or a pharmaceutically acceptable fluvoxamine salt.
• the invention according to claim 3 is the therapeutic or prophylactic agent according to claim 1 or 2, wherein the salt is fluvoxamine maleate.
• the invention according to claim 4 is the therapeutic or prophylactic agent according to any one of claims 1 to 3, wherein the dose is 25-200 mg / day in terms of fluvoxamine maleate.
• the invention according to claim 5 is the therapeutic or prophylactic agent according to claim 4, which is administered 1 to 4 times per day.
• the invention according to claim 6 is the therapeutic or prophylactic agent according to any one of claims 1 to 5, which is administered in combination with another therapeutic agent.
• the present inventor has eagerly searched for drugs effective for dementia, particularly peripheral symptoms, and investigated various compositions.
• fluvoxamine which has been conventionally used as a therapeutic agent for depression, is not effective for dementia. I got the knowledge of heels. The result of repeated clinical trials. The effect that fluvoxamine is effective in the treatment and prevention of dementia was confirmed, and the present invention was completed.
• the following effects are achieved. It does not cause concomitant symptoms (side effects) such as aspiration, falls, oversedation, cognitive decline, myocardial infarction, etc., and pseudoaldosteronism does not appear even after long-term administration, and it is used for treatment and prevention of dementia It is valid.
• side effects such as aspiration, falls, oversedation, cognitive decline, myocardial infarction, etc.
• pseudoaldosteronism does not appear even after long-term administration, and it is used for treatment and prevention of dementia It is valid.
• the present invention is a therapeutic or preventive agent for dementia and behavioral psychological symptoms (BSPD).
• the application target is patients with dementia.
• it is effective for patients with BSPD as peripheral symptoms of dementia.
• BSPD behavioral psychological symptoms
• BPSD BPSD
• Rough deeds (abuses and violence), refusal of care Damaged delusions, delusions of being stolen, day / night reversal, night delirium ⁇ , desire to return home Incontinence, peeing, food / collection (collection), gathering filthy acts / facial sexual behavior Depression
• the patient is mainly human, but can be applied to mammals other than humans.
• “pharmaceutically acceptable fluvoxamine salt” is a salt of fluvoxamine.
• Preferred salts include, for example, sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, sulfate, hydrogen sulfate, phosphate, acid phosphate, isonicotinate , Acetate, lactate, salicylate, citrate, acid citrate, tartrate, oleate, tannate, pantothenate, acid tartrate, ascorbate, succinate, maleate, Gentisate, fumarate, gluconate, glucaronate, saccharinate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p- Examples include but are not limited to toluenesulfonate and pamoate
• fluvoxamine or a pharmaceutically acceptable fluvoxamine salt is formulated according to routine procedures as a pharmaceutical composition adapted for administration to a subject.
• Drugs containing fluvoxamine as an active ingredient have already been commercialized, marketed and used as a moisturizer. Therefore, it is also possible to use a commercially available product as it is as a therapeutic or prophylactic agent of the present invention.
• the agent of the present invention can be used, for example, in the following dosage forms.
• Other dosage forms suitable for use may also be used. Aerosol solution, elixir, capsule, soft capsule, granule, eye ointment, transdermal preparation, suspension, emulsion, suppository, powder, syrup, tablet, syrup, injection, patch, troche, ointment, poultice, aromatic liquid, liniment, limonade, lotion Agent
• Excipients used include, for example, (a) inert diluents such as mannitol, sorbitol, calcium carbonate, pregelatinized starch, lactose, calcium phosphate or sodium phosphate, (b) povidone, copovidone, hydroxypropyl methylcellulose Granulating and disintegrating agents such as corn starch, alginic acid, crospovidone, sodium starch glycolate, croscarmellose or polacrilin potassium, (c) binders such as microcrystalline cellulose or gum arabic, and (d ) Lubricants such as magnesium stearate, stearic acid, fumaric acid or talc.
• inert diluents such as mannitol, sorbitol, calcium carbonate, pregelatinized starch, lactose, calcium phosphate or sodium phosphate
• povidone, copovidone hydroxypropyl methylcellulose Granulating and disintegrating agents
• Method of administration examples include, but are not limited to, the following methods.
• the mode of administration is at the discretion of the clinician.
• Enema administration Intravenous administration
• Arterial administration Intramuscular administration
• Subcutaneous administration Intradermal administration
• Intrathecal administration Intraperitoneal administration
• Intravesical administration Transdermal administration Transmucosal administration Oral Administration Vaginal suppository
• dose The exact dose employed will also depend on the route of administration and the severity of the disease or disorder, and will depend on the judgment of the clinician and the environment of each patient.
• an itching agent it is common for adults to take 50 mg per day as the initial dose of fluvoxamine maleate, gradually increasing to a maximum of about 150 mg per day, and orally administered in divided doses twice a day.
• the therapeutic agent for dementia and BSPD is preferably 25-200 mg / day in terms of fluvoxamine maleate. Compared with less than 25 mg / day, a greater effect can be expected in this range, and the possibility of occurrence of side effects is significantly worse than in the range exceeding 200 mg / day. In view of body weight, 1-25 mg / kg is preferable.
• the dosing period may be, for example, 1 month, 3 months, 6 months, 1 year, or a longer period such as the lifetime of the patient.
• adverse effects can be caused when a composition of the invention is administered concurrently with another therapeutic agent, such as, but not limited to, other therapeutic agents can be harmful. It is advantageous to administer at doses below the threshold at which
• Example 1 A randomized, double-blind study of 76 patients with dementia who required hospitalization due to behavioral psychological symptoms was conducted using risperidone, Yokukansan, and fluvoxamine (Fluvoxa mine) was administered. Risperidone group 25 patients Yokukansan group 26 patients Fluvoxamine group 25 patients
• DIEPSS rating scale for extrapyramidal symptoms was not significantly different at baseline, but was significantly higher with risperidone at the endpoint.
• risperidone had significantly more constipation and muscle tonicity, and there was one sudden death.
• BSPD can be treated and prevented without side effects, and the burden of care for family members and facility staff can be reduced, which helps the care industry.

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• 2012
  • 2012-05-11 JP JP2012109985A patent/JP2013237619A/ja active Pending
  • 2012-11-30 WO PCT/JP2012/081189 patent/WO2013168315A1/fr not_active Ceased

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