JP2019218282A - Pharmaceutical composition for treating bad dream disorder - Google Patents

Abstract

To provide a method for preventing a bad dream, and a method for changing a bad dream into a good dream.SOLUTION: A pharmaceutical composition for treating bad dream disorder contains saffron or extract thereof as an active ingredient.SELECTED DRAWING: None

Description

  The present invention relates to a pharmaceutical composition for treating a nightmare disorder comprising saffron, and more particularly, to a pharmaceutical composition or a food composition for treating a nightmare disorder comprising saffron or an extract thereof, ferulic acid or a salt thereof and phosphatidylcholine. .

  Nightmares have plagued countless people throughout human history. Nightmares impair sleep recovery from fatigue and are associated with many psychiatric problems. Negative emotions associated with stressful events are also said to trigger nightmares, as they are often found in (traumatic) post-traumatic stress disorder (PTSD). The prevalence of nightmare disorders is significantly higher in patients with any mental illness than in the general population. For example, about 3/4 in patients with PTSD, about half in patients with borderline personality disorder, and at least 10% in patients with schizophrenia often experience nightmares. And there are many reports that nightmares are associated with mental distress, self-harm, and suicide (see, for example, Non-Patent Document 1).

The Classification Manual for Mental Illness / Mental Disorders (DSM-5) prepared by the American Psychiatric Association defines nightmaring disorders as follows.
A. Prolonged, very unpleasant, recallable dreams occur repeatedly. The dream usually includes content that seeks to avoid threats to survival, safety, or physical integrity, and generally occurs late in the main sleep period. B. Upon waking up from an unpleasant dream, the person quickly becomes aware and conscious. C. The sleep disorder causes clinically significant distress or impairment of functioning in social, occupational, or other important areas. D. The nightmare is not due to the physiological effects of substances (eg, drugs of abuse, pharmaceuticals). E. FIG. With co-existing mental or medical illnesses, the main components of unpleasant dream appeals are not fully understood.

  On the other hand, it has been conventionally known that saffron has a sleep promoting effect. For example, Patent Document 1 reports that safranal, an essential oil component contained in saffron, has an effect of enhancing sleep and sedation. In Patent Document 2, it has been found that saffron or crocin, a component of gardenia, is effective in improving sleep efficiency and sedating. Furthermore, Non-Patent Document 2 reports the anxiolytic and hypnotic effects of saffron water extract and its components crocin and safranal in mice. However, there is no known link between nightmares and the effect of saffron on sleep promotion.

JP 2014-024800A JP 2011-246357 A

Reck S.A. et al. , Nightmares in the general population: Identifying poten- tial factor. Soc Psychiatry Psychiatr Epidemio; (2017) 52: 1123-1133. Hosseinzadeh H, Noraei NB. , Anxioltic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, inmice. Phytother Res. 2009 Jun; 23 (6): 768-74.

  According to our analysis, nightmares have the following characteristics: One is discomfort that is chased, killed, or killed by someone. In other aspects, the most distressed parts of current life are increasing and appearing in nightmares. For example, a boss who is scolded at work and sweating and suffering itself appears as a dream, and when he gets up, he experiences strong anxiety and depression. However, no method has been found so far to eliminate nightmares and even to turn nightmares into good dreams.

  The present inventors have conducted intensive studies on many medicines and health foods for treatment of mental illness, and as a result, a subject diagnosed as having a nightmare disorder has taken 10 to 400 mg of saffron pistil powder to achieve a nightmare. I found a case that turns into. Here, a good dream can be defined as a dream that wants to see again, feels happiness, gains self-confidence, and works positively for human psychology.

That is, the present invention includes the following embodiments.
(1) A pharmaceutical composition for treating nightmaring disorders, comprising saffron or an extract thereof as an active ingredient.
(2) The pharmaceutical composition for treating a nightmare disorder according to (1), wherein the saffron is a dried product of saffron pistil.
(3) The pharmaceutical composition for treating nightmaring disorders according to (1) or (2) for suppressing the onset of depression or post-traumatic stress disorder (PTSD) in subjects who have experienced fear or discomfort. .
(4) The pharmaceutical composition for treating nightmaring disorders according to (1) or (2), which is used in combination with a therapeutic agent for depression or dementia.
(5) The pharmaceutical composition for treating nightmaring disorders according to (3), for enhancing the effect of a therapeutic agent for depression or dementia.
(6) A food composition for improving nightmare disorders, which comprises saffron or an extract thereof as an active ingredient.
(7) The food composition for improving nightmare disorder according to (4), further comprising ferulic acid or a salt thereof and phosphatidylcholine.
(8) The food composition for improving nightmaring disorders according to (4) or (5), which is a functional food or supplement.
(9) A veterinary pharmaceutical composition, feed or animal supplement comprising saffron or an extract thereof as an active ingredient.
(10) The veterinary pharmaceutical composition, feed or veterinary supplement according to (9) for reducing stress of an animal suffering from nightmares.

  The pharmaceutical composition of the present invention can convert a nightmare into a good nightmare by administering to a subject diagnosed with or having a nightmare disorder.

(1) Active ingredient The pharmaceutical composition and food composition of the present invention contain saffron or an extract thereof as an active ingredient. Saffron (Crocus sativa) is a plant belonging to the genus Crocus of the family Iridaceae, and dried stamens are used as spices and are known as medicinal plants having effects such as analgesia, sedation, and stomachic. . As the active ingredient of the present invention, an extract extracted from saffron dry pistil powder or water, alcohol, other organic solvent or a mixed solvent thereof under room temperature conditions or heating conditions is used.

  The method for producing the saffron pistil extract is not particularly limited, and can be performed by a conventional method. At the time of extraction, it may be used as it is, but it is preferable to perform extraction after performing processing such as drying, shredding, and pulverization in consideration of extraction efficiency. The extraction can be performed by a method of immersion in an extraction solvent or a super (sub) critical extraction method using a supercritical fluid or a subcritical fluid. In order to increase the extraction efficiency, homogenization may be performed with stirring or in an extraction solvent. The extraction temperature is not particularly limited, but when using a method of immersing in an extraction solvent, it is preferable to set the temperature to about 5 ° C. to a temperature equal to or lower than the boiling point of the extraction solvent. It can be adjusted depending on the pressure and the type of extraction solvent. The extraction time varies depending on the type of extraction solvent and the extraction temperature, but is preferably about 1 hour to 14 days.

  Examples of the extraction solvent include water, lower alcohols such as methanol, ethanol, propanol and isopropanol, polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, dipropylene glycol and glycerin, and ethers such as ethyl ether and propyl ether. Solvents, esters such as butyl acetate and ethyl acetate, and ketones such as acetone and ethyl methyl ketone can be used, and one or two or more solvents are selected from these solvents. Further, physiological saline, phosphate buffer, phosphate buffered saline, and the like may be used. When the super (sub) critical extraction method is used, one or more supercritical fluids or subcritical fluids such as water, carbon dioxide, ethylene, propylene, ethanol, methanol, and ammonia can be used.

  The extract from the solvent obtained from the pistil of saffron can be used as it is, but the concentrated and dried extract may be redissolved in water or a polar solvent, or subjected to purification treatment such as decolorization, deodorization, and desalination. Or after fractionation by column chromatography or the like. The extract, the processed product thereof, and the fractionated product may be freeze-dried after each treatment and fractionation, and may be dissolved in a solvent before use. It is of course possible to mix commercially available saffron extracts (saffron extract BG (Maruzen Pharmaceutical), safran tincture (Ogi Pharmaceutical), Harbex saffron extract (Koei Kogyo), etc.).

(2) Action and Effect The composition of the present invention containing saffron or an extract thereof as an active ingredient (hereinafter referred to as “the composition of the present invention”) can be used for the purpose of preventing or treating nightmare disorders. It is effective for healthy people and patients with sleep disorders. For example, sleep apnea syndrome and REM sleep behavior disorder are likely to occur during REM sleep, and thus may coexist with nightmares experienced during REM sleep and worsen the symptoms. In such a case, turning a nightmare into a good dream may improve breathlessness and discomfort, and may also improve sleep apnea syndrome and REM sleep behavior disorder. It is also empirically known that drugs such as dopaminergic drugs, drugs for treating Parkinson's disease, and β-blockers that cross the blood-brain barrier cause nightmares. The pharmaceutical compositions of the present invention are believed to improve sleep quality and reduce the side effects of the drugs that cause these nightmares by turning nightmares into good nightmares. As mentioned above, in addition to sleep disorders, nightmares may be associated with mental illness by being accompanied by strong anxiety and fear. For example, it is known that nightmares are more likely to have depression, and it is also known that they may have nightmares as a precursor to depression, which is useful for treating other mental illnesses.

  The mechanism by which the compositions of the present invention convert nightmares into good dreams is not clear and is not bound by any theory, but is believed to be based on the basic principles outlined below. It is said that what humans experience is changed from short-term memory to long-term memory during sleep. During sleep, a network formed by a wide range of brain regions such as the medial temporal lobe that controls memory, the prefrontal cortex that controls judgment and thinking, the posterior cingulate gyrus that integrates information, and the outer inferior parietal lobe work during sleep, It is thought to be related to the fixation and forgetting of memories experienced during the period. If a great deal of stress is applied at this time, the network will malfunction and manifest itself as a nightmare. It is presumed that the active ingredient according to the present invention acts to make this network work well, turning nightmares into good dreams and reducing stress. If fear or unpleasant experiences are too great, not only nightmares but also hard memories during the day suddenly rise, triggering negative emotions such as fear, pain, anger, sadness, helplessness, so-called flashback (PTSD). Therefore, an effect of suppressing the onset of depression and post-traumatic stress disorder (PTSD) in a subject by exchanging nightmares into good dreams to reduce stress is also expected.

(3) Pharmaceutical composition The active ingredient comprising saffron or an extract thereof in the present invention can be used alone, but a composition having an action of transforming a nightmare into a good dream by being mixed with various compositions. Can be obtained. The obtained composition is preferably used as a drug, a quasi-drug, a cosmetic, or a food, in view of its effectiveness in improving nightmare disorders.

  Pharmaceutical compositions for the treatment of nightmares disorders containing the above-mentioned saffron or its extract as an active ingredient, if necessary, usually include drugs, oily ingredients, which are blended in pharmaceuticals, quasi-drugs, cosmetics, foods, etc. , Humectants, powders, pigments, emulsifiers, solubilizers, detergents, ultraviolet absorbers, thickeners, fragrances, resins, alcohols, nutrient enhancers, seasonings, etc. can be added as appropriate, and further Can be used in combination with a drug for treating mental illness.

  For example, it is known that people with nightmare disorders are more likely to have anxiety and worries, and are more likely to develop depression because of difficulty in recovering from fatigue due to sleep. People with nightmares have poor stress tolerance and fail to adapt and become depressed if they have to deal with complex relationships and work in the workplace. People who are depressed due to nightmare disorder are hardly treated with antidepressants, and once they take time off, they can hardly return to work. Behind the difficulty of returning to work from depression due to depression are other mental illnesses behind depression, which are likely to make antidepressants ineffective. The pharmaceutical composition of the present invention is effective for ameliorating nightmaring disorders that are the background of depression, and as a result, is also effective for treating depression itself. That is, the pharmaceutical composition of the present invention is also useful as a therapeutic agent for depression accompanied by nightmare disorder.

  Here, "depression" is defined in DSM-5 (Mood disorders, depression clinically diagnosed by specialists (eg, psychiatrists, psychoanalysts, psychologists, and therapists)). , As well as depression that can be clinically diagnosed by a psychiatrist, but nonetheless can be severe and long-term). As non-limiting examples, clinically diagnosed depression includes dementia, acute depression, schizophrenia, and other clinical depressive disorders classified in DSM-5.

  When the pharmaceutical composition of the present invention is combined with an active ingredient of an antidepressant, the therapeutic effect of the active ingredient on depression can be enhanced. The active ingredient that can be combined with the pharmaceutical composition of the present invention is not particularly limited as long as it is used for treating depression. As antidepressants, for example, tricyclic antidepressants such as amitriptyline, amoxapine, clomipramine, desipramine, doxepin, and imipramine, citalopram, fluoxetine, fluvoxamine, paroxetine, and selective serotonin reuptake inhibitors such as sertraline, phenelzine And monoamine oxidase (MAO) inhibitors such as tranylcypromine, and serotonin / noradrenaline reuptake inhibitors (SNRIs) such as milnacipran and duloxetine. The active ingredient of the antidepressant may be contained as a component of the pharmaceutical composition of the present invention, or may be prepared as a separate pharmaceutical composition from the pharmaceutical composition of the present invention. Selection of such active ingredients as antidepressants, titration and dosing schedule are within the skill of those skilled in the art.

  In another aspect, the pharmaceutical composition of the present invention can enhance the therapeutic effect of the active ingredient on dementia by combining it with the active ingredient of a therapeutic agent for dementia. The active ingredient that can be combined with the pharmaceutical composition of the present invention is not particularly limited as long as it is used for treating dementia. As an example, the active ingredient contained in the therapeutic agent for Alzheimer's dementia may be, for example, donepezil hydrochloride, or the active ingredient contained in a cerebral circulation improving agent, such as ifenprodil tartrate, ibudilast and nicergoline, or the brain. The active ingredient contained in the metabolism improving drug, for example, amantadine hydrochloride may be used. The active ingredient of the therapeutic agent for dementia may be contained as a component of the pharmaceutical composition of the present invention, or may be prepared as a separate pharmaceutical composition from the pharmaceutical composition of the present invention. Good. The selection of the active ingredient of such a drug for treating dementia, the selection of the dose, the administration schedule, and the like are within the skill of those skilled in the art.

  In the present invention, “dementia” includes Alzheimer's disease, vascular dementia, Lewy body dementia, frontotemporal dementia, HIV-related dementia, and the like (Merck Manual, 18th edition). Alternatively, it includes the following disease or disorder names classified as “dementia” belonging to “delirium, dementia, amnestic disorder, and other cognitive disorders” defined in DSM-5: Alzheimer-type cognition Dementia due to sickness, vascular dementia, or other common diseases. Alternatively, it includes the following disease or disorder names classified as “organic psychiatric disorders including symptomatics” defined in ICD-10: Alzheimer's disease type dementia, vascular dementia, and the like. Dementia of other diseases, unspecified dementia. Examples of diagnostic criteria or evaluation methods used for diagnosing dementia at clinical sites include, for example, the revised Hasegawa-type simplified intelligence evaluation scale (HDS-R).

  In the present invention, the term “effective” or “effective” in the treatment means that subjective or objective reduction or elimination of one or more symptoms characteristic of the target mental disease or disorder is recognized. Can mean that. To be objectively recognized may be a fact that improvement of the disease or disorder is recognized by an index of a diagnostic standard or an evaluation scale that can be used for diagnosis of the target disease or disorder in a clinical setting, or a family member. The improvement such as reduction or elimination of one or more symptoms characteristic of the disease or disorder may be recognized from the viewpoint of a third party such as the attending physician or surrounding humans.

  In the present invention, the term “effective” or “effective” for prevention means that the disease or disorder is obtained by administering the pharmaceutical composition of the present invention in a situation where the subject can be expected to suffer from the disease or disorder. May mean that at least one or more symptoms that can be expected from the onset do not develop, or that their severity or progression is reduced. Prediction of the occurrence of the disease or disorder may be based on the results of medical tests such as genetic tests or tests such as CT or MRI, or may be based on medical considerations such as environmental changes or the start of pharmacotherapy. Is also good.

  In the present invention, when the active ingredient is used as a medicament for treating nightmaring disorders, the dose varies depending on the condition, age, and administration method of the patient to be administered. The dose is preferably about 1 to 400 mg / day, more preferably about 10 to 100 mg / day.

(4) Food composition When the composition of the present invention is used as a food composition, foods, health foods, functional foods, supplements, and the like obtained by adding or mixing the above-mentioned active ingredients to various foods and drinks are included. . When these food compositions are ingested, they exert the effect of turning human nightmares into good dreams, as in the case of the pharmaceutical composition. Therefore, a person having such a nightmare disorder gradually improves such symptoms by ingesting the food composition, and also leads to prevention of such a disease for a healthy person.

  The content of the extract obtained from the pistil of saffron, which is the active ingredient of the present invention, differs depending on the form of food and drink. For example, as in the case of pharmaceuticals, it may be in the form of powders, granules, tablets, capsules containing 1 to 400 mg, preferably 10 to 100 mg, of saffron extract per serving. These can be taken one to three times a day depending on the symptoms and purpose.

  The food composition for improving nightmare disorders of the present invention preferably contains ferulic acid or a salt thereof and phosphatidylcholine in addition to saffron or an extract thereof. This is because these additives are also known to act on the central nervous system and have an effect on some mental disorders such as dementia and developmental disorders (see, for example, Japanese Patent No. 5807018, No. 2017-186334).

  The food composition of the present invention has, as an additive, at least one selected from the group consisting of ferulic acid, esters thereof, pharmaceutically acceptable salts thereof, and pharmaceutically acceptable solvates thereof. Contains two compounds. The ester of ferulic acid of the present invention includes a monoester or diester obtained by esterifying one or both of a hydroxyl group and a carboxyl group of ferulic acid with an aliphatic or aromatic alcohol or an aliphatic or aromatic carboxylic acid. As the pharmacologically acceptable salts of ferulic acid and its esters, those usually used in the art may be used, for example, inorganic salts such as hydrochloride, sulfate and carbonate, maleate, fumaric acid and the like. Organic salts such as salts and sulfonates may be used. Those pharmacologically acceptable solvates include those commonly used in the art, such as solvates with water, alcohols or ethers. Any compound selected from the group consisting of ferulic acid, its esters, their pharmacologically acceptable salts, and their pharmacologically acceptable solvates can be used. Among them, ferulic acid, Preferred are their pharmacologically acceptable salts or their pharmacologically acceptable solvates. At least one compound selected from the group consisting of ferulic acid, its esters, their pharmacologically acceptable salts and their pharmacologically acceptable solvates, is extracted from any plant or seed -It may be purified or chemically synthesized. A rice bran-derived product is preferably extracted and purified from a plant, and such a rice bran-derived ferulic acid is, for example, Feldex (trademark) of Tsukino Food Industry Co., Ltd. (Japanese Patent Publication No. 7-78032). Publication). As a chemical synthesis method, for example, a method based on a condensation reaction of vanillin and malonic acid is known (Journal of American Chemical Society, 74, 5346 (1952)).

  Further, the food composition of the present invention preferably contains phosphatidylcholine as an additive. Phosphatidylcholine is a generic term for phospholipids in which choline is a phosphate ester bond as a hydrophilic part of glycerophospholipid and has a structure in which two fatty acids are ester-bonded to a glycerol skeleton as a hydrophobic part. Naturally occurring phosphatidylcholine often has one fatty acid as a saturated fatty acid such as palmitic acid and the other fatty acid as an unsaturated fatty acid such as oleic acid or linoleic acid. Unsaturated fatty acids are one component of phospholipids that constitute biological membranes, and are known to be released from phospholipids by various lipases to cause various biological reactions. It has been shown to increase nicotinic acetylcholine receptor responses through activation, increase glutamate release from presynaptic terminals, and promote synaptic transmission for prolonged periods. It has also been found that arachidonic acid, one of the unsaturated fatty acids, acts as a retrograde messenger for synaptic transmission long-term potentiation (LTP), a cell model of learning and memory. These phosphatidylcholines have been reported to be useful for the prevention or treatment of diseases or conditions associated with cognitive impairment (eg, Patent No. 5769912).

  In recent years, a multi-component preparation useful for improving cognitive function of a patient such as Alzheimer's disease or delaying or preventing a decrease in cognitive function has been reported (for example, JP-T-2015-524777). For example, a first component comprising one or more vitamins selected from the group consisting of one or more vitamin B groups, vitamin C, vitamin D, vitamin E, coenzyme Q10, vitamin K and folic acid, selenium, lithium , A second component comprising one or more elements selected from the group consisting of magnesium and molybdenum, a third component comprising one or more omega-3 fatty acids, and trimethylglycine, N-acetylcysteine, S A multi-component formulation comprising a fourth component comprising one or more amino acids selected from the group consisting of adenosylmethionine, L-tryptophan and glutathione. These formulations improve neurological function in subjects with major deficiencies in areas such as low levels of endogenous growth factors, low levels of antioxidants, high inflammation, low levels of major vitamins, and low levels of healthy synaptic components, In particular, it has been reported that it can address cognitive decline in the elderly and those with mild cognitive impairment (referred to as MCI). The food composition of the present invention, when added to such a multi-component preparation, turns a nightmare into a good dream and reduces the stress of the subject, thereby synergistically activating nerve function with the above-mentioned multi-component preparation. Is expected to improve dementia.

  When the composition of the present invention is used as a functional food or supplement, the dosage form is not particularly limited, for example, capsules, syrups, tablets, pills, powders, granules, drinks, injections, infusions, Examples include nasal drops, eye drops, suppositories, patches, sprays and the like. In the formulation, other pharmaceutically acceptable preparations, such as excipients, disintegrants, lubricants, binders, antioxidants, coloring agents, antiaggregants, absorption promoters, solubilizing agents And a stabilizer can be added as appropriate.

(5) Animal pharmaceutical composition, feed or animal supplement The composition of the present invention can also be used as a feed (including pet food) or an animal drug. Many experimental animals are used for human sleep studies, and it is known that mammals such as mice, rats, dogs and cats have a complex sleep mechanism similar to humans. In fact, dogs and mice have been used in narcolepsy research and many results have been obtained. It has already been reported that animals, including dogs, dream (K. Louise and MA Wilson, Neuron Vol. 29, 145-156 (2001)). Like dogs, dogs sleep in two levels: REM sleep and non-REM sleep, and they seem to dream during REM sleep. During REM sleep, the brain processes events that occur while awake, and the dreams that dogs see are thought to be closer to everyday life, such as chasing a ball or spraying with their owner. It may be a nightmare under severe stress. For example, it is considered that a dog who does not like bathing has a nightmare based on the experience of being shampooed or the dog afraid of loud noises hearing fireworks and lightning. Therefore, by using the active ingredient of the present invention in a veterinary pharmaceutical composition, feed or animal supplement, stress on animals, particularly pets such as dogs and cats, can be reduced, and suffering caused by nightmares can be reduced.

  The feed or veterinary drug of the present embodiment uses saffron or an extract thereof as a main raw material, but the raw materials used in a normal compound feed are appropriately compounded according to the type of animal, development stage, breeding environment such as region, etc. May be. Such raw materials include, for example, cereals or processed cereals (corn, milo, barley, wheat, rye, oat, millet, flour, wheat germ powder, etc.), bran (bran, rice bran, corn gluten feed, etc.), vegetable Oil cakes (soy oil cake, sesame oil cake, cottonseed oil cake, peanut cake, sunflower cake, safflower cake, etc.), animal raw materials (skim milk powder, fish meal, meat and bone meal, etc.), minerals (calcium carbonate, calcium phosphate, salt, anhydrous silica) Acids, etc.), vitamins (vitamin A, vitamin D, vitamin E, vitamin K, vitamin B1, vitamin B2, vitamin B6, vitamin B12, calcium pantothenate, nicotinamide, folic acid, etc.), amino acids (glycine, methionine, etc.) , Yeasts such as brewer's yeast, fine powders of inorganic substances (crystalline cellulose, talc, silica, muscovite, zeo Ito, etc.) and the like.

  The form of the feed of the present embodiment is not particularly limited, and examples thereof include powder, granule, paste, pellet, capsule (hard capsule, soft capsule), and tablet. The animals to which the feed of the present invention is fed are not particularly limited, and include, for example, livestock such as cows, horses, pigs, sheep, chickens (including both broilers and hens), turkeys, and ducks. And the like, experimental animals such as mice, rats, and guinea pigs, and pets such as dogs and cats.

[Production Example 1]
40 liters of a 50% by weight aqueous solution of ethanol was added to 1 kg of the dried pulverized saffron pistil, and extraction was performed for 2 hours while stirring at room temperature. Thereafter, the extract was filtered to collect the filtrate. On the other hand, the remaining insolubles were collected again, and the same extraction operation was performed to collect the filtrate. The first filtrate and the second filtrate were combined and the solvent was removed to obtain an extract of saffron pistils. In the following examples, cases were shown in which a supplement containing 12.5 mg of a saffron pistil extract was administered in one to several units.

<Example 1>
38-year-old woman, housewife I always dreamed of dreaming when I was young. Over the past two years or so, the frequency of dreams has increased, and all dreams have been nightmares. When 50 mg of saffron was administered, nightmares began to decrease from the third day, disappeared in one week, and pleasant dreams and happy dreams appeared. This kind of good dream has never been seen before.

<Example 2>
A 14-year-old male, a sophomore in junior high school suffered nightmares every day for several months. I was afraid to sleep, my rhythm of life was broken, and I couldn't go to school more days. Then, when 12.5 mg of saffron was administered, the nightmare disappeared, and a pleasant and bright dream was started. This made it easy to commute to school.

<Example 3>
A 32-year-old man, depression, office worker, had been treating for depression, had a very strong nightmare for a few weeks. The nightmare was a scream from a boss who was not good at the company, and was repeatedly sweating and awakening. So, when 25mg of saffron was added to 50mg for 3 days and then 50mg, the nightmare disappeared, and the good experiences of the old days of fun began to appear in dreams.

<Example 4>
A 52-year-old male teacher visited the hospital with chief complaints of difficulty falling asleep, awakening, and nightmares. Sleep onset and premature awakening improved with various sleeping pills, but nightmares worsened. Then, when 50 mg of saffron powder was administered, the effect appeared in 2 days, and it became a pleasant and happy dream instead of a nightmare.

<Example 5>
Alcohol nightmare case / 32-year-old male He started drinking alcohol heavily in his early twenties and suffered from alcohol abuse and chronic alcoholism. Attempts to stop alcohol worsened nightmares and made it impossible to stop alcohol abuse.

  After trying various sleeping pills and antidepressants, severe nightmares did not improve. Starting with 25 mg of saffron, the third night, when it reached 75 mg, the nightmare disappeared, and on the contrary, she began to have a pleasant dream. He also improved his sleep disorders.

<Example 6>
Case of nightmare due to sleep disorder / 55-year-old man / office worker I had a sleep disorder and a deep sleep disorder, and at the same time, my dream was a nightmare overtaken by something and a painful experience at the company. The use of sleeping pills improved sleep impairment, but had no effect on arousal and nightmares. No drugs such as alcohol were used. Starting with 25 mg of saffron, at 50 mg, the nightmare disappeared, and on the contrary, it became a hopeful good dream.

<Example 7>
Junior high school nightmare disorder / age 14 / female Insomnia and nightmares began to occur frequently shortly after the new semester. As a result, she was rejected from school. After more than three months, I went to a psychiatrist. However, there were no sleeping pills available to junior high school students, and treatment was significantly more difficult because parents did not want treatment in Western medicine. Then, starting with 12.5 mg of saffron, and taking 25 mg of saffron two weeks later, the nightmare disappeared, and she became a positive dream and was able to safely go to junior high school.

(Example of prescription)
Formulation examples using saffron or an extract thereof are described below, but the present invention is not limited to these formulation examples.
[Formulation Example 1] Soft capsule (1) Saffron extract [Production Example 1] 12.5 mg
(2) 7.5 mg of ferulic acid (98%)
(3) Phosphatidylcholine (containing 40%) 10.0 mg
(4) Linseed oil 142.0mg
(5) Rice wax 14.0mg
(6) Glycerin fatty acid ester 14.0 mg
Production method: (1) to (6) were filled in a soft capsule (200 mg / particle) having a pork gelatin film by a filling machine.

[Formulation Example 2] Tablet (1) Saffron extract [Production Example 1] 15.0 mg
(2) 1.5 mg of magnesium stearate
(3) Lactose 60.0mg
(4) Silicon Dioxide Remaining Production Method: (1) to (3) were tableted with a tableting machine to obtain tablets having a diameter of 10 mm and a weight of 300 mg.

[Formulation Example 3] Beverage (1) Saffron extract [Production Example 1] 5.0 (% by weight)
(2) Erythritol 1.0
(3) Citric acid 0.1
(4) Stevia 0.01
(5) Purified water 93.89
Production method: (1) to (5) were uniformly mixed.

Claims (10)

  A pharmaceutical composition for treating nightmare disorders, comprising saffron or an extract thereof as an active ingredient.   The pharmaceutical composition according to claim 1, wherein the saffron is a dried pistil of saffron.   The pharmaceutical composition for treating nightmaring disorders according to claim 1 or 2, for suppressing the onset of depression or post-traumatic stress disorder (PTSD) in a subject who has experienced fear or discomfort.   The pharmaceutical composition for treating nightmaring disorders according to claim 1 or 2, which is used in combination with a therapeutic agent for depression or dementia.   The pharmaceutical composition for treating nightmaring disorders according to claim 4, for enhancing the effect of a therapeutic agent for depression or dementia.   A food composition for improving nightmare disorders, comprising saffron or an extract thereof as an active ingredient.   The food composition for improving nightmare disorder according to claim 6, further comprising ferulic acid or a salt thereof and phosphatidylcholine.   The food composition for improving nightmare disorders according to claim 6 or 7, which is a functional food or a supplement.   An animal pharmaceutical composition, feed or animal supplement comprising saffron or an extract thereof as an active ingredient. 10. The veterinary pharmaceutical composition, feed or animal supplement according to claim 9 for reducing stress in animals suffering from nightmares.