WO2008013215A1 - Préparation orale induisant le sommeil, et préparation orale pour soigner l'insomnie liée au stress - Google Patents

Préparation orale induisant le sommeil, et préparation orale pour soigner l'insomnie liée au stress Download PDF

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Publication number
WO2008013215A1
WO2008013215A1 PCT/JP2007/064641 JP2007064641W WO2008013215A1 WO 2008013215 A1 WO2008013215 A1 WO 2008013215A1 JP 2007064641 W JP2007064641 W JP 2007064641W WO 2008013215 A1 WO2008013215 A1 WO 2008013215A1
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WIPO (PCT)
Prior art keywords
serine
sleep
oral
oral preparation
stress
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PCT/JP2007/064641
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English (en)
Japanese (ja)
Inventor
Li Han
Kousuke Hayamizu
Mitsuhiro Furuse
Original Assignee
Fancl Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from JP2006206140A external-priority patent/JP3999249B2/ja
Application filed by Fancl Corporation filed Critical Fancl Corporation
Publication of WO2008013215A1 publication Critical patent/WO2008013215A1/fr

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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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • 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
    • 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
    • A61P25/20—Hypnotics; Sedatives

Definitions

  • Oral agent for inducing sleep oral agent for improving stress insomnia
  • the present invention relates to a sleep inducer and a stress insomnia improving agent.
  • insomnia is a state in which the amount of sleep time necessary to maintain a person's health is insufficient in terms of quantity or quality, which hinders social life and is also concerned consciously.
  • temporary insomnia for a few days
  • short-term insomnia for 1-3 weeks
  • long-term insomnia for more than a month.
  • the causes of insomnia vary, but often they are associated with some form of stress, and the longer this stress is, the more likely the symptoms of insomnia become.
  • the use of sleeping pills, tranquilizers, stress relievers, etc. is commonly used.
  • the effect of improving insomnia is greatly influenced by the psychological state of the subject and the surrounding environment, and is limited by the characteristics of the action point of the drug used, side effects and drug dependence. There are many things. Therefore, it is necessary to develop new medicines and functional foods in order to improve the drawbacks of these sleeping pills, tranquilizers and stress relievers.
  • the present inventors found an anxiolytic effect on a compound having a serine unit such as serine phosphatidylserine, or glycine, phosphatidic acid, etc., and filed a patent application (Japanese Patent Application No. 2005-029114). . This time, as an extension of the study, we discovered that administration of L-serine and the like showed a remarkable sleep-inducing effect under stress loading conditions, and found that effect.
  • the present invention provides a new sleep inducer and stress insomnia improving agent.
  • the present inventors have found that serine, phosphoserine, Each of phosphatidylserine, lysophosphatidylserine, acetylserine, or cysteine is L-type, and these compounds are found to have sleep-inducing or stress-induced insomnia-improving effects, and are effective and effective by oral prescription. It was confirmed. That is, the present invention is based on the following means.
  • Each of serine, phosphoserine, phosphatidylserine, lysophosphatidylserine, acetylylserine, or cysteine, which is a compound having a serine unit, is L-type, and one or more selected from these compounds
  • An oral agent for inducing sleep characterized by containing two or more.
  • Each of serine, phosphoserine, phosphatidylserine, lysophosphatidylserine, acetylylserine, or cysteine, which is a compound having a serine unit, is L-type, and one or more selected from these compounds
  • Serine is produced by any of the following methods: protein hydrolysis, chemical synthesis, enzymatic method, fermentation method, extraction from natural raw materials and purification (1) (2) An oral preparation for inducing sleep or an oral preparation for improving stress insomnia.
  • the lysophosphatidylserine product extracted from a natural raw material, or produced by enzymatic base conversion reaction or phosphatidylserine fatty acid dissociation, (1) or (2) An oral preparation for sleep induction or an oral preparation for improving stress insomnia.
  • the phosphoserine, cysteine, and acetylylserine are produced by any one of a protein hydrolysis method, a chemical synthesis method, an enzymatic method, a fermentation method, or a natural raw material extraction / purification method.
  • Item 3. An oral preparation for inducing sleep or an oral preparation for improving stress insomnia according to item 1 or 2.
  • the content of one or more selected from serine, phosphoserine, phosphatidylserine, lysophosphatidylserine, acetylylserine, or cysteine, which is a compound having a serine unit, is 5% by mass or more.
  • a sleep-inducing or stress-induced insomnia characterized by containing the oral agent for inducing sleep or the oral agent for improving stress-induced insomnia as described in! / Of any one of (1) to (7) Oral medicine for symptom improvement.
  • FIG. 1 is a diagram showing sleep behavior in L-serine (L-Ser) concentration-based administration groups in Example 1.
  • FIG. 2 Sleep behavior of L-serine (L-Ser) and D-serine (D_Ser) administration groups in Example 2
  • L-Ser L-serine
  • D_Ser D-serine
  • FIG. 3 Diagram showing sleep behavior of L-serine (L-Ser), O-phospho-L-serine (Phos_S), O-acetyl-L-serine (Ace-S), and L-cysteine (L-Cys) administration groups in Example 3. .
  • FIG. 4 is a view showing sleep behavior in a group administered with L-serine (L-Ser), glycine (Gly), and La lysophosphatidylserine (Lyso-PS) in Example 4.
  • L-Ser L-serine
  • Gly glycine
  • Lyso-PS La lysophosphatidylserine
  • FIG. 5 is a view showing sleep behavior of a group administered with L-a-phosphatidylserine (PS), L-a phosphatidylethanolamine (PE), and L a phosphatidylcholine (PC) in Example 5.
  • PS L-a-phosphatidylserine
  • PE L-a phosphatidylethanolamine
  • PC L a phosphatidylcholine
  • FIG. 6 is a diagram showing the L_Serine structure.
  • FIG. 7 is a view showing a 0-phospho-L-Serine structure.
  • FIG. 8 shows a structure of L-a-phosphatidylserine (L-a-Phosphatidy® Serine).
  • FIG. 9 Diagram showing the structure of L—a lysophosphatidylserine (L-a-Lyso-Phosphatidy ⁇ Serine).
  • FIG. 10 Diagram showing the structure of O-acetyl-L-Serine (O-Acety-L-Serine).
  • FIG. 11 is a diagram showing an L-Cysteine structure.
  • FIG. 12 shows a structure of L—a phosphatidylcholine (L-a-Phosphatidy® Choline).
  • FIG. 13 is a diagram showing the structure of L—a phosphatidylethanolamine (L-a-Phosphatidy ⁇ Ethanolamin).
  • FIG. 14 is a diagram showing a D_serine structure.
  • FIG. 15 is a graph showing the effect of improving sleep maintenance by serine intake in Example 6.
  • FIG. 16 is a graph showing the sleep improvement effect of serine intake in Example 6.
  • FIG. 17 is a graph showing the sleep improvement effect of serine intake by a person who feels stress in Example 6.
  • a compound having a serine unit having an L-type structure and a cysteine having an L-type structure could be confirmed.
  • the effective serine unit and cysteine of the present invention shown below are compounds having an L-type structure.
  • the compound having a serine unit is a compound having a serine unit represented by the following general formula 1.
  • stronger activity can be obtained in the case of an R-based phosphate group connected to this serine unit.
  • Cysteine (Cys) is represented by the chemical formula “H—S—CH (NH 2) COOH”.
  • Serine according to the present invention can be produced by any of protein hydrolysis, chemical synthesis, enzymatic method, and fermentation method.
  • serine is a structural component of tissues, even those with low yields can be extracted and purified from natural raw materials such as animals and plants.
  • it can also be produced from components derived from animals, plants, etc. by producing, extracting and purifying by chemical treatment such as phosphoserine and phosvitin.
  • the selenium according to the present invention is not intended to limit the manufacturing method.
  • the phosphoserine according to the present invention can be produced by any of protein hydrolysis, chemical synthesis, and enzymatic methods.
  • Phosphoserine is known as a precursor of serine biosynthesis. Since it is a protein component containing phosphoric acid, it can be produced by extracting and purifying even low yields from animals and plants. Examples of proteins rich in phosphoserine include casein and phosvitin. Furthermore, it can also be produced from components derived from animals, plants, etc., for example, casein, phosvitin, etc. by chemical treatment, extraction, and purification.
  • the production method of phosphoserine according to the present invention is not particularly limited.
  • the phosphatidylserine related to the present invention is a natural product such as soybean, cottonseed and other plant species. It can be produced by extraction from offspring, egg yolk, seafood, poultry and meat. Alternatively, a phosphatidylserine-rich phospholipid raw material can be produced by carrying out a phosphatidyl group transfer reaction using these produced lecithins.
  • the production method of phosphatidylserine according to the present invention is not particularly limited.
  • the lysophosphatidylserine according to the present invention can be produced by extraction from natural plant seeds such as soybeans and cottonseed, egg yolk, seafood, and animal meat.
  • a lysophosphatidylserine-rich phospholipid raw material can be produced by carrying out a phosphatidyl group transfer reaction using lysolecithin produced therefrom. Since lysophosphatidylserine is obtained by dissociating the fatty acid moiety of phosphatidylserine, it can be produced, extracted, and purified from phosphatidylserine by enzyme or chemical treatment.
  • the production method of lysophosphatidylserine according to the present invention is not particularly limited.
  • Acetylserine according to the present invention can be produced by any of protein hydrolysis, chemical synthesis, and enzymatic methods. Acetylserine is known as an intermediate of cysteine biosynthesis in microorganisms. Acetylserine according to the present invention does not particularly limit the production method.
  • the cystine according to the present invention can be produced by any of protein hydrolysis, chemical synthesis, and enzymatic methods.
  • cysteine is a structural component of tissues, those with low yields can be extracted and purified from animals and plants.
  • cysteine is one in which the hydroxyl group oxygen atom of serine is substituted with a sulfur atom, it can be produced from serine by chemical treatment, extraction and purification.
  • the cystine according to the present invention does not particularly limit the production method.
  • Serine, phosphoserine, phosphatidylserine, lysophosphatidylserine, acetylylserine, or cysteine which is a compound having a serine unit, is a natural type or an L type produced by any of the methods described above. Is available.
  • Fig. 6 shows L-serine
  • Fig. 7 shows O-Phospho-L-Serine
  • Fig. 8 shows L-a-phosphatidylserine
  • Fig. 9 Is L-a-lysophosphatidylserine (L-a-Lyso-Phosphatidyl-Serine)
  • Figure 10 shows O-acetylyl-L —Serine (O-Acety to L-Serine)
  • Fig. 11 is L-Cysteine
  • Fig. 12 is L- ⁇ -phosphatidinorecholine (L-a-Phosphatidy ⁇ Choline)
  • Fig. 13 is L-a-phosphatidinorethanolamine (L-Phosphatidyl-Ethanolamin is shown.
  • serine, phosphoserine, phosphatidylserine, lysophosphatidylserine, acetylylserine, and cysteine produced by the above method are used as active ingredients.
  • commercially available serine, phosphine, phosphatidylserine, lysophosphatidylserine, facetylserine, cystine as active ingredients and can be formulated in combination with known non-toxic pharmaceutical carriers according to conventional methods. Good! /
  • the oral agent for inducing sleep and the oral agent for improving stress insomnia according to the present invention can be orally administered in various dosage forms.
  • the oral agent include tablets, granules, powders, Examples include solid agents such as pushells and soft capsules, solutions such as solutions, suspensions and emulsions, and freeze-dried preparations.
  • parenteral administration agents in addition to injections, suppositories, sprays, and transdermal absorption agents are possible, but oral intake is preferable for convenience of users.
  • non-toxic carrier for pharmaceutical use examples include glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, and albumin. , Water, physiological saline and the like. If necessary, conventional additives such as stabilizers, lubricants, wetting agents, emulsifiers, binders and the like can be appropriately added.
  • the oral agent for inducing sleep and the oral agent for improving stress insomnia which are compounds having a serine unit
  • the dosage is appropriately selected and determined according to the patient's age, weight, symptoms, degree of disease, administration schedule, formulation, etc.
  • the dose is about 0.01 to 10 g / kg body weight per day. It may be administered once to several times a day.
  • Test condition 1 applies to Examples;! In each example, the experiment was conducted at different times and compounds.
  • Test animals Egg breeder male chickens (Julia, 5 or 6 days old) were used for the test. Prior to sample application, the test animals were grouped according to their body weights, with 6 to 10 birds in pairs.
  • Test sample The following reagents were prepared by dissolving in 0.85% saline containing 0.1% Evans blue (additional 5% DMSO when necessary).
  • Test method Ten reagents were administered to the ventricles of chicken chicks using a microsyringe. Also In the Control group, 101 ventricle was injected with 0.85% saline containing 0.1% Evans blue.
  • Noturn 1 Make a voluntary movement and use it as an index of anxiety.
  • Pattern 2 It may sound like it stands in the middle state, but it is not an index.
  • Pattern 3 Sleeping behavior can be used as an indicator of sleeping behavior by closing eyes or sitting and dropping head.
  • Test condition 2 applies to Example 5.
  • Test animals Egg breeder male chickens (Julia, 4 or 5 days old) were used for the test. Prior to sample application, the test animals were grouped according to their body weights, with 6 to 10 birds in pairs. Breeding conditions: Under the condition of 29 ⁇ 1 ° C, commercial feed (Toyohashi Feed Co., Ltd., AX) and water were freely fed.
  • Test sample The following reagents were prepared by suspending each in Tris-HC1 Buffer containing 0.1% Evans Blue.
  • L-a-phosphatidinoreserin 98%, derived from bovine brain
  • Test method Ten reagents were administered to the ventricles of chicken chicks using a microsyringe.
  • the Control group received 10 ⁇ l ventricle of Tris HC1 Buffer containing 0.1% Evans Blue.
  • Example 1 the following compounds were used as test samples. The behavior of chickens was classified into patterns. The measurement results (seconds) are shown in Table 1. Figure 1 shows the sleep behavior.
  • the L-serine 0.82 mol administration group showed clear sleep-inducing effects and stress-induced insomnia improvement effects compared to the control group.
  • Example 2 the following compounds were used as test samples. The behavior of chickens was classified into patterns. The measurement results (seconds) are shown in Table 2. Figure 2 shows sleep behavior.
  • the L-serine administration group showed significantly the same sleep induction effect and stress insomnia improvement effect as Example 1 compared to the control group.
  • Example 3 the following compounds were used as test samples. The behavior of chickens was classified into patterns. The measurement results (seconds) are shown in Table 3. Figure 3 shows sleep behavior.
  • L-acetylserine which has a serine unit, showed a tendency to induce sleep and improve stress insomnia compared to the control group.
  • the O phospho-L-serine administration group in which the R group connected to the serine unit is a phosphate group showed a stronger remarkable sleep-inducing effect or stress-induced insomnia-improving effect.
  • the sleep-inducing effect is significantly increased in the same manner as the compound having the serine unit, Stress insomnia improved.
  • Example 4 the following compounds were used as test samples. The behavior of chickens was classified into patterns. The measurement results (seconds) are shown in Table 4. Figure 4 shows sleep behavior.
  • the glycine administration group and the La-lysophosphatidylserine (Lyso-PS) administration group have sleep-inducing effects and stress-induced insomnia-improving effects as compared to the control group. Showed a trend.
  • Example 5 the following compounds were used as test samples.
  • Figure 5 shows the sleep behavior of chickens.
  • PS, Lyso-PS, PE and PC are phospholipids with a structure common to the lipid part.
  • PS and Lyso-PS show sleep-inducing effects and stress-induced insomnia improvement effects, while PE and PC The fact that such an effect was not shown confirmed that the serine unit has a sleep-inducing effect and an effect of improving stress insomnia.
  • the inner volume was filled with a soft capsule filling machine to 250 mg.
  • a soft capsule filling machine For the coating, a commonly used gelatin and glycerin mixture was used. After drying, as a result of conducting a standard test on grains that have passed liquid leakage inspection, shape selection inspection, and visual inspection, capsule long diameter, force capsule short diameter, capsule total weight, capsule film weight, capsule contents weight, film moisture content It was confirmed that the drug product satisfies various standards such as quantity, disintegration time, acid value, peroxide value, general viable cell count, coliform bacteria, etc.
  • Example 6 serine was used as an evaluation product, and a double-blind cross-over test was performed by the following method and content for comparison with a placebo product and a non-essential amino acid glycine.
  • Test samples trehalose (manufactured by Hayashibara Shoji Co., Ltd .; placebo product), glycine (manufactured by Kyowa Hakko Kogyo Co., Ltd .; comparative product), L-serine (manufactured by Kyowa Hakko Kogyo Co., Ltd .; test product).
  • Study period Ingestion period is 4 consecutive days, washout is 10 days or more as raw shellfish IJ, and this is repeated three times (each placebo, glycine, and serine) (see Table 6 Test schedule)
  • Non-patent literature Mitsugu Oguri et al., Psychiatry, Vol.27 (7), 791-799, 1985
  • Example:! ⁇ 5 is a test administered directly to the chick cerebral ventricles
  • This Example 6 is a test taken orally by humans. This study confirmed that oral administration provided a mechanism of action for humans and that oral ingestion was effective.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Neurosurgery (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Anesthesiology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'objet de l'invention consiste à élaborer un agent induisant le sommeil et un agent soignant l'insomnie liée au stress. À cet effet, une préparation orale induisant le sommeil comprend un ou plusieurs éléments choisis parmi la sérine, la phosphosérine, la phosphatidylsérine, la lysophosphatidylsérine, acétylsérine (qui sont des composés ayant une unité sérine) et une cystéine, chacune sous forme L.
PCT/JP2007/064641 2006-07-28 2007-07-26 Préparation orale induisant le sommeil, et préparation orale pour soigner l'insomnie liée au stress WO2008013215A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2006-206140 2006-07-28
JP2006206140A JP3999249B2 (ja) 2005-08-08 2006-07-28 睡眠誘導剤、ストレス性不眠症改善剤

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WO2008013215A1 true WO2008013215A1 (fr) 2008-01-31

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CN (1) CN101437507A (fr)
TW (1) TW200816988A (fr)
WO (1) WO2008013215A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010035026A1 (fr) * 2008-09-23 2010-04-01 Merck Sharp & Dohme Ltd Utilisation d'amplificateurs d'activité de nmda pour traiter l’hypersomnie, un état de veille réduit ou une vigilance réduite
JP2010235490A (ja) * 2009-03-31 2010-10-21 Fancl Corp ホスファチジルセリン含有カプセル及びカプセル充填用ホスファチジルセリン組成物
WO2012043481A1 (fr) * 2010-09-30 2012-04-05 国立大学法人東京海洋大学 Composition contenant de la 2-acyl-lysophosphatidylsérine et son procédé de production

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6279714B2 (ja) * 2014-03-25 2018-02-14 株式会社ヤクルト本社 睡眠の質改善剤
KR101998821B1 (ko) * 2017-12-28 2019-07-10 제주파나텍 (주) 황칠 발효물 및 l-세린을 이용한 수면 장애 개선용 조성물

Citations (1)

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Publication number Priority date Publication date Assignee Title
JP2005247841A (ja) * 2004-02-04 2005-09-15 Fancl Corp 抗不安剤

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Publication number Priority date Publication date Assignee Title
JP2005247841A (ja) * 2004-02-04 2005-09-15 Fancl Corp 抗不安剤

Non-Patent Citations (3)

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Title
ASECHI M. ET AL.: "Intracerebroventricular injection of L-serine analogs and derivatives induces sedative and hypnotic effects under an acute stressful condition in neonatal chicks", BEHAV. BRAIN RES., vol. 170, no. 1, 3 June 2006 (2006-06-03), pages 71 - 77, XP005408399 *
ASECHI M. ET AL.: "L-Serine no Noshitsu Toyo ni yoru Niwatori Hina no Stress Kodo wa Keigen Sareru", 2005 NENDO (HEISEI 17 NEN) THE JAPANESE SOCIETY FOR ANIMAL SCIENCES DAI 105 KAI TAIKAI KOEN YOSHISHU, 25 August 2005 (2005-08-25), pages 7, XP003020697 *
KOUTOKU T. ET AL.: "Central administration of phosphatidylserine attenuates isolation stress-induced behavior in chicks", NEUROCHEM. INT., vol. 47, no. 3, August 2005 (2005-08-01), pages 183 - 189, XP004953073 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010035026A1 (fr) * 2008-09-23 2010-04-01 Merck Sharp & Dohme Ltd Utilisation d'amplificateurs d'activité de nmda pour traiter l’hypersomnie, un état de veille réduit ou une vigilance réduite
JP2010235490A (ja) * 2009-03-31 2010-10-21 Fancl Corp ホスファチジルセリン含有カプセル及びカプセル充填用ホスファチジルセリン組成物
WO2012043481A1 (fr) * 2010-09-30 2012-04-05 国立大学法人東京海洋大学 Composition contenant de la 2-acyl-lysophosphatidylsérine et son procédé de production
US9290781B2 (en) 2010-09-30 2016-03-22 National University Corporation Tokyo University Of Marine Science And Technology Composition containing 2-acyl-lysophosphatidylserine and method for producing the same
JP6025143B2 (ja) * 2010-09-30 2016-11-16 国立大学法人東京海洋大学 ２−アシル−リゾホスファチジルセリン含有組成物及びその製造方法

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CN101437507A (zh) 2009-05-20
TW200816988A (en) 2008-04-16

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