US20070207134A1 - Functional food for ameliorating engogenous melatonin secretion rhythm and functional food for ameliorating circadian rhythm - Google Patents
Functional food for ameliorating engogenous melatonin secretion rhythm and functional food for ameliorating circadian rhythm Download PDFInfo
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- US20070207134A1 US20070207134A1 US10/599,446 US59944605A US2007207134A1 US 20070207134 A1 US20070207134 A1 US 20070207134A1 US 59944605 A US59944605 A US 59944605A US 2007207134 A1 US2007207134 A1 US 2007207134A1
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- whey
- agent
- rhythm
- improving
- melatonin secretion
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/20—Milk; Whey; Colostrum
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
- A61P5/04—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin for decreasing, blocking or antagonising the activity of the hypothalamic hormones
Definitions
- the present invention relates to functional food for improving an endogenous melatonin secretion rhythm and functional food for improving a circadian rhythm, which are expected to prevent or ameliorate sleep disorder or prolonged sleep latency, a material for the active component of such food, and an agent for phase-adjusting or enhancing the amplitude of an endogenous melatonin secretion rhythm and an agent for improving a circadian rhythm, which may prevent or ameliorate various disorders associated with disorders of the endogenous melatonin secretion rhythm or the circadian rhythm.
- circadian rhythm disorder such as sleep disorder, or disorder of an endogenous melatonin secretion rhythm, which is a possible factor for the circadian rhythm disorder
- melatonin N-acetyl-5-methoxytryptamine secreted mainly from the corpus pineale.
- Melatonin is a hormone synthesized from tryptophan through serotonin under the action of NAT (N-acetyltransferase) as a rate-limiting enzyme.
- This hormone is believed to be involved in introduction of photoperiodic information in photoperiodic mammals and exert an influence on reproduction, body weight, metabolic regulation, circadian rhythm control, as well as nervous and endocrine functions. Further, since the melatonin secretion level of the corpus pineale is low in the day time and high in the night time, melatonin is believed to be one of the sleep-modulatory substances.
- melatonin secretion rhythm in patients with sleep disorder or circadian rhythm disorder is different from that of healthy people in that the amplitude is decreased or the phase is either advanced or delayed.
- Patent Publication 1 reports that oral administration of melatonin from an external source to artificially regulate a melatonin rhythm has an effect on non-24-hour sleep-wake syndrome, jet lag syndrome, shift-work sleep syndrome, delayed sleep phase syndrome, or the like, accompanied by prolonged sleep latency, insomnia, waking in bad mood, jet lag, reverse of day and night, or the like.
- Patent Publication 2 proposes a composition for improving the quality of sleep, containing as the active component muramyl peptide prepared by hydrolysis from the cell wall of non-pathogenic lactic acid bacteria.
- the improvement in the quality of sleep taught in this publication is achieved by increasing the length of the non-REM sleep phase through induction of sleep by the immune system, so that this way of improving the quality of sleep is completely different from the improvement of the endogenous melatonin secretion level.
- an agent for phase-adjusting or enhancing an amplitude of an endogenous melatonin secretion rhythm comprising whey as an active component.
- an agent for improving a circadian rhythm comprising whey as an active component.
- functional food for improving an endogenous melatonin secretion rhythm such as preventing or ameliorating sleep disorder or prolonged sleep latency, comprising the above-mentioned agent for phase-adjusting or enhancing an amplitude of an endogenous melatonin secretion rhythm.
- functional food for improving a circadian rhythm such as preventing or ameliorating sleep disorder or prolonged sleep latency, comprising the above-mentioned agent for improving a circadian rhythm.
- a method for phase-adjusting or enhancing an amplitude of an endogenous melatonin secretion rhythm comprising the step of orally administering to an animal in need thereof an effective amount of an agent for phase-adjusting or enhancing an amplitude of an endogenous melatonin secretion rhythm comprising whey as an active component.
- a method for improving a circadian rhythm comprising the step of orally administering to an animal in need thereof an effective amount of an agent for improving a circadian rhythm comprising whey as an active component.
- whey for the manufacture of an agent for phase-adjusting or enhancing an amplitude of an endogenous melatonin secretion rhythm, or for the manufacture of functional food for phase-adjusting or enhancing an amplitude of an endogenous melatonin secretion rhythm.
- whey for the manufacture of an agent for improving a circadian rhythm, or for the manufacture of functional food for improving a circadian rhythm.
- the agent for phase-adjusting or enhancing the amplitude of an endogenous melatonin secretion rhythm, and the agent for improving a circadian rhythm according to the present invention contain whey, which has been taken as food, as the active component, the present agents may be taken daily and continuously, are excellently safe, and are expected to prevent or ameliorate sleep disorder or prolonged sleep latency, such as non-24-hour sleep-wake syndrome, jet lag syndrome, shift-work sleep syndrome, sleep apnea syndrome, and middle-age sleep disorder, which are believed to be associated with the disorders of such rhythms.
- the functional food according to the present invention contains the agent for phase-adjusting or enhancing the amplitude of an endogenous melatonin secretion rhythm or the agent for improving a circadian rhythm of the present invention
- the present functional food may prevent or ameliorate various symptoms such as sleep disorder or prolonged sleep latency, without administration of exogenous melatonin.
- FIG. 1 is a graph illustrating the comparison among the groups of the melatonin concentration in the corpus pineale at 12:00 performed in Examples 1 and 2.
- FIG. 2 is a graph illustrating the comparison among the groups of the melatonin concentration in the corpus pineale at 0:00 performed in Examples 1 and 2.
- FIG. 3 is a graph illustrating the comparison among the groups of the NAT activity in the corpus pineale at 12:00 performed in Examples 3 and 4.
- FIG. 4 is a graph illustrating the comparison among the groups of the NAT activity in the corpus pineale at 0:00 performed in Examples 3 and 4.
- the agent for phase-adjusting or enhancing the amplitude of an endogenous melatonin secretion rhythm is capable of preventing or ameliorating various disorders caused by disorder of an endogenous melatonin secretion rhythm, exhibits at least one of a phase-adjusting effect and an amplitude enhancing effect on the rhythm, and contains whey as the active component.
- the agent for improving a circadian rhythm according to the present invention exhibits an effect of preventing or ameliorating various disorders caused by circadian rhythm disorder, and contains whey as the active component.
- the active component, whey includes an aqueous fraction of milk obtained by removing all or most of the casein protein and the like from milk according to a common procedure, and may be, for example, acid whey and/or cheese whey.
- the acid whey may include fermented milk whey obtained by fermentation of milk with lactic acid bacteria, and casein whey containing an aqueous fraction of milk obtained by adding acid to milk to remove all or most of the casein protein and the like according to a common procedure.
- Fermented milk whey is particularly preferred for its excellent ability to phase-adjust or enhance the amplitude of an endogenous melatonin secretion rhythm or to improve a circadian rhythm.
- the fermented milk whey may usually be a fermented milk whey prepared by fermentation of milk with lactic acid bacteria, or by symbiotic fermentation of milk with lactic acid bacteria and a yeast.
- the starting material milk may be animal milk, such as cow's milk, goat's milk, or sheep's milk; vegetable milk, such as soy bean milk; or processed milk thereof, such as skim milk, reconstituted milk, powdered milk, or condensed milk.
- the milk may be in the form of a mixture.
- the solid content of the milk is not particularly limited.
- the solid non-fat content is typically about 9 mass %.
- the solid non-fat content may be increased to some extent.
- the fermented milk whey obtained in the production of fermented milk may be separated from other milk components before use, but when the fermented milk whey is to be made into the functional food or the like to be discussed later, such other milk components are not necessarily separated.
- the lactic acid bacteria may be those of the genus Streptococcus, Lactococcus, Lactobacillus, Bifidobacterium, or the like, with Lactobacillus being preferred.
- Lactobacillus may include Lactobacillus bulgaricus, Lactobacillus helveticus, Lactobacillus casei, Lactobacillus acidophilus, and Lactobacillus fermentum, with Lactobacillus helveticus being particularly preferred.
- Lactobacillus helveticus ATCC 15009 Lactobacillus helveticus ATCC 521
- Lactobacillus helveticus CM4 strain deposited at National Institute of Advanced Industrial Science and Technology, International Patent Organism Depositary under Accession Number BERM BP-6060 on Aug. 15, 1997) (referred to as CM4 hereinbelow) may be used, with CM4 being particularly preferred.
- CM4 has been deposited under the above-mentioned accession number under the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure. All restrictions on the availability to the public of this strain will be irrevocably removed upon the granting of a patent.
- the lactic acid bacteria are preferably in the form of a pre-cultured starter having sufficiently high activity.
- the initial cell count may preferably be about 10 5 -10 7 cells/ml.
- yeast When the fermented milk whey is to be used in functional food, such as foods for specified health uses, yeast may be used for symbiotic fermentation for improved flavor and palatability.
- the strain of the yeast is not particularly limited, and may preferably be, for example, yeast of the genus Saccharomyces, such as Saccharomyces cerevisiae.
- the content of the yeast may suitably be selected depending on the purpose.
- the fermentation may be carried out by culturing one or more kinds of the lactic acid bacteria in a medium, or culturing a mixture of one or more kinds of the lactic acid bacteria and one or more kinds of the yeast in a medium.
- the medium may be those composed only of one or more kinds of the milk components mentioned above, or those optionally contain additional components, such as yeast extract; vitamins, e.g. ascorbic acid; amino acids, e,g. cysteine; salts, e.g. sodium chloride; sugars, e.g. glucose, sucrose, raffinose, or stachyose; stabilizers, e.g. gelatine; and flavoring agents.
- the fermentation may be performed usually by static or stirred culture, for example at 20 to 50° C., preferably 30 to 45° C., at the initial pH of 6.0 to 7.0, and may be terminated when the cell count becomes 10 7 cells/ml or higher at pH 5.0 or lower.
- the milk may be subjected to high-temperature pasteurization before fermentation.
- the fermented milk whey may be separated from curd by means of a common separating operation.
- the fermented milk whey as the active component is to be used in the functional food to be discussed later, the fermented milk containing the whey may be used as it is without separation, if so desired, or the extent of separation may suitably be decided
- the casein whey may be prepared by, when solid milk, such as whole milk or skim milk is used, dissolving the milk in distilled water, adding, for example, lactic acid, citric acid, acetic acid, tartaric acid, fumaric acid, malic acid, gluconic acid, or adipic acid to adjust the acidity to a level suitable for removing protein, typically casein, and separating the whey component (aqueous fraction) by a common procedure, such as membrane filtration.
- the milk maybe subjected to high temperature pasteurization before the acid is added.
- the acid may usually be added in an amount for achieving 1.0 to 4.0% acidity, depending on the kind of the acid or the like.
- the cheese whey may be prepared in the ordinary cheese production, by coagulating milk with rennet to form curd, and separating the whey component from the curd by centrifugation or the like.
- the milk may be subjected to high temperature pasteurization before the rennet is added.
- the dose of the sour milk whey as the active component in the agent for phase-adjusting or enhancing the amplitude of an endogenous melatonin secretion rhythm or in the agent for improving a circadian rhythm is not particularly limited, taking the continuity of administration into account, and may usually be not less than 0.001 g per kg body weight per day, preferably not less than 0.01 g per kg body weight per day, in terms of freeze-dried powder.
- the agent for phase-adjusting or enhancing the amplitude of an endogenous melatonin secretion rhythm or the agent for improving a circadian rhythm of the present invention may optionally contain components others than the whey as desired, having the function of phase-adjusting or enhancing the amplitude of an endogenous melatonin secretion rhythm or improving a circadian-rhythm.
- the agent for phase-adjusting or enhancing the amplitude of an endogenous melatonin secretion rhythm or the agent for improving a circadian rhythm according to the present invention may be in the form of whey with or without processing, for example, a whey concentrate obtained by concentrating whey through vacuum concentration or the like process, or a dried whey powder obtained by drying whey through freeze-drying or spray drying.
- the agent for phase-adjusting or enhancing the amplitude of an endogenous melatonin secretion rhythm or the agent for improving a circadian rhythm according to the present invention may be administered usually through an oral route.
- the agent may be administered even after the symptoms of sleep disorder caused by disorder of an endogenous melatonin secretion rhythm or of a circadian rhythm are developed, or in the seasons to prevent such symptoms, either continuously daily or intermittently.
- the functional food for improving an endogenous melatonin secretion rhythm according to the present invention contains the agent for phase-adjusting or enhancing the amplitude of an endogenous melatonin secretion rhythm
- the functional food for improving a circadian rhythm according to the present invention contains the agent for improving a circadian rhythm.
- the functional food may be functional food, such as foods for specified health uses, claiming prevention or amelioration of symptoms caused by disorder of an endogenous melatonin secretion rhythm or a circadian rhythm, such as prevention or amelioration of sleep disorder or prolonged sleep latency.
- the functional food may optionally contain additives, such as sugars, proteins, lipids, vitamins, minerals, flavoring agents, or mixtures thereof. Further, the milk components from which the whey is separated, may also be contained.
- the content of the whey as the active component may suitably be selected depending on the form or kind of the food.
- the content may suitably be selected also depending on the continuity of intake of the functional food or the like factors, and is not particularly limited.
- a suitable content may be usually 1 to 100 mass %.
- the various functional food mentioned above may be in the form of, for example, fermented milk products, such as yogurt or lactic acid bacteria beverage, processed food and beverage containing whey, dry powders, tablets, capsules, granules, or the like,
- the dose and the timing of administration of the various functional food of the present invention are not particularly limited, and it is preferred to take the functional food in such an amount that the above-mentioned dose of the active component is generally achieved
- the present functional food may be taken continuously or intermittently before or after the symptoms of sleep disorder or the like caused by disorder of an endogenous melatonin secretion rhythm or a circadian rhythm are developed.
- skim milk was dissolved in distilled water at a solid content of 9 mass %, subjected to high temperature pasteurization in an autoclave at 105° C. for 10 minutes, allowed to cool to the room temperature, inoculated with 3 mass % of a pre-cultured CM4 starter, and cultured at 37° C. for 24 hours, to thereby obtain fermented milk.
- This fermented milk was centrifuged at 12000 G for 20 minutes for removing the solids, to prepare fermented milk whey.
- skim milk was dissolved in distilled water at a solid content of 9 mass %, subjected to high temperature pasteurization in an autoclave at 105° C. for 10 minutes, and allowed to cool to the room temperature. Lactic acid was added to increase the acidity to 2.2%. Then the product was centrifuged at 12000 G for 20 minutes for removing the solids, to prepare casein whey.
- Example 1 Each of the obtained fermented milk whey (Example 1) and casein whey (Example 2) was diluted with distilled water to 10 mass %, and used in the following animal test as a drinking water. As a control, distilled water without whey was also used in the test.
- Fifty one male Wistar rats at 3 weeks of age were pre-bred for 1 week.
- the rats were allowed free access to solid feed (trade name MF, manufactured by ORIENTAL YEAST CO., LTD.) and distilled water.
- the daily light-dark cycle during the pre-breeding was set such that the light cycle was from 8:00 to 20:00 and the dark cycle was for 12 hours after that.
- the rats were divided into three groups of 17 animals each, i.e., Group (1) taking distilled water (control), Group (2) taking 10 mass % fermented milk whey (Example 1), and Group (3) taking 10 mass % casein whey (Example 2), and bred with free access to the respective drinks and solid feed for 1 month.
- Group (2) taking 10 mass % fermented milk whey (Example 1) Group (3) taking 10 mass % casein whey (Example 2)
- bred with free access to the respective drinks and solid feed for 1 month.
- 9 animals in each group was slaughtered at 12:00, and the remaining 9 animals in each group at 0:00, and the corpus pineale of each animal was taken out of the brain. 200 ⁇ l of 0.01 M perchloric acid was added, and the mixture was homogenized and centrifuged. The melatonin content in the resulting supernatant was measured, whereas the precipitate was collected for quantification of proteins.
- the melatonin content was measured using Melatonin EIA Kit (trade name, manufactured by IBL Hamburg).
- the proteins were quantified by the Bradford method using Bio-Rad Protein Assay (trade name, manufactured by Bio-Rad).
- the results of the measurement of melatonin content at 12:00 are shown in FIG. 1 , and those at 0:00 in FIG. 2 .
- the statistical significance was determined by the student-newman-keuls test.
- the melatonin concentration at 12:00 was significantly lower than that in Group (1) taking distilled water (significance level p ⁇ 0.05), and the melatonin concentration at 0:00 was significantly higher than that in Group (1) taking distilled water (significance level p ⁇ 0.05) and that in Group (3) taking the casein whey (significance level p ⁇ 0.01).
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Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
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JP2004-106153 | 2004-03-31 | ||
JP2004106153 | 2004-03-31 | ||
JP2004-166498 | 2004-06-04 | ||
JP2004166498 | 2004-06-04 | ||
PCT/JP2005/006244 WO2005094849A1 (ja) | 2004-03-31 | 2005-03-31 | 内因性メラトニン分泌リズム改善用機能性食品、及び概日リズム改善用機能性食品 |
Publications (1)
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US20070207134A1 true US20070207134A1 (en) | 2007-09-06 |
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Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
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US10/599,446 Abandoned US20070207134A1 (en) | 2004-03-31 | 2005-03-31 | Functional food for ameliorating engogenous melatonin secretion rhythm and functional food for ameliorating circadian rhythm |
US11/952,839 Expired - Fee Related US8067034B2 (en) | 2004-03-31 | 2007-12-07 | Functional food for ameliorating endogenous melatonin secretion rhythm and functional food for ameliorating circadian rhythm |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
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US11/952,839 Expired - Fee Related US8067034B2 (en) | 2004-03-31 | 2007-12-07 | Functional food for ameliorating endogenous melatonin secretion rhythm and functional food for ameliorating circadian rhythm |
Country Status (6)
Country | Link |
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US (2) | US20070207134A1 (ja) |
EP (1) | EP1741437A4 (ja) |
JP (1) | JP4891069B2 (ja) |
CN (1) | CN1960739B (ja) |
TW (1) | TW200533299A (ja) |
WO (1) | WO2005094849A1 (ja) |
Cited By (4)
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CN102526217A (zh) * | 2011-10-13 | 2012-07-04 | 宁波海逸生物科技有限公司 | 一种增强免疫力、促进睡眠功能保健药物配方 |
US10695383B2 (en) | 2012-03-02 | 2020-06-30 | National Institute Of Advanced Industrial Science And Technology | Circadian rhythm-improving agent |
US11331353B2 (en) | 2014-03-25 | 2022-05-17 | Kabushiki Kaisha Yakult Honsha | Sleep quality improver |
US11617772B2 (en) | 2018-09-11 | 2023-04-04 | Direct Digital Llc | Nutritional supplements and therapeutic compositions comprising probiotics |
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US20150147298A1 (en) * | 2006-07-24 | 2015-05-28 | CortControl, Inc. | Sleep enhancement with cortisol reduction medical food |
RU2482689C1 (ru) * | 2011-12-01 | 2013-05-27 | Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Вологодская государственная молочнохозяйственная академия имени Н.В. Верещагина" | Способ производства кефира с функциональными свойствами |
WO2015133122A1 (ja) * | 2014-03-04 | 2015-09-11 | カルピス株式会社 | 鎮静用の自律神経調整剤及び日周リズム改善剤 |
JP6127169B2 (ja) * | 2016-02-15 | 2017-05-10 | 三基商事株式会社 | 睡眠改善剤 |
US20200009170A1 (en) * | 2016-09-13 | 2020-01-09 | Megumi Tanaka | Sleep display agent property and method for improving sleep disorders |
JP7428480B2 (ja) * | 2019-06-06 | 2024-02-06 | 雪印メグミルク株式会社 | 睡眠改善用組成物及び組成物を含む食品、医薬品、飼料 |
CN111903844B (zh) * | 2020-08-07 | 2022-05-13 | 中国热带农业科学院热带作物品种资源研究所 | 一种提高青贮饲料发酵品质的方法及其制得的饲料 |
WO2022196488A1 (ja) * | 2021-03-15 | 2022-09-22 | 森永乳業株式会社 | Qolを改善するための組成物 |
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DE3827833C1 (ja) * | 1988-08-17 | 1989-12-28 | Horst 5419 Herschbach De Meinhardt | |
DE9411450U1 (de) * | 1994-07-14 | 1994-10-06 | Delta Patent Invest AG, Vaduz | Molkepräparate |
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2005
- 2005-03-31 CN CN2005800175804A patent/CN1960739B/zh not_active Expired - Fee Related
- 2005-03-31 JP JP2006511785A patent/JP4891069B2/ja active Active
- 2005-03-31 WO PCT/JP2005/006244 patent/WO2005094849A1/ja active Application Filing
- 2005-03-31 EP EP05727955A patent/EP1741437A4/en not_active Withdrawn
- 2005-03-31 US US10/599,446 patent/US20070207134A1/en not_active Abandoned
- 2005-03-31 TW TW094110323A patent/TW200533299A/zh unknown
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2007
- 2007-12-07 US US11/952,839 patent/US8067034B2/en not_active Expired - Fee Related
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US6284243B1 (en) * | 1995-07-14 | 2001-09-04 | Calpis Co., Ltd. | Physiologically functional food having brain function-improving, learning ability-enhancing, and memory-enhancing functions |
US6235719B1 (en) * | 1996-10-03 | 2001-05-22 | Laboratoire Oenobol, S.A. | Uses of compositions with α-lactalbumin base |
US6534304B1 (en) * | 1997-09-26 | 2003-03-18 | Calpis Co., Ltd. | Lactobacillus helveticus bacterium having high capability of producing tripeptide, fermented milk product, and process for preparing the same |
US20050074500A1 (en) * | 1999-01-11 | 2005-04-07 | Calpis Co. Ltd. | Method for producing fermented milk containing angiotensin converting enzyme inhibitory peptide and method for producing whey |
US6900180B1 (en) * | 1999-01-20 | 2005-05-31 | N.V. Nutricia | Pharmaceutical compositions for alleviating discomfort |
US6444203B2 (en) * | 1999-12-20 | 2002-09-03 | Compagnie Gervais Danone | Administering bacteria to improve sleep |
US20040097714A1 (en) * | 2001-07-13 | 2004-05-20 | Jean-Louis Maubois | Method for obtaining a tgf-beta enriched protein fraction in activated form protein fraction and therapeutic applications |
Cited By (4)
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CN102526217A (zh) * | 2011-10-13 | 2012-07-04 | 宁波海逸生物科技有限公司 | 一种增强免疫力、促进睡眠功能保健药物配方 |
US10695383B2 (en) | 2012-03-02 | 2020-06-30 | National Institute Of Advanced Industrial Science And Technology | Circadian rhythm-improving agent |
US11331353B2 (en) | 2014-03-25 | 2022-05-17 | Kabushiki Kaisha Yakult Honsha | Sleep quality improver |
US11617772B2 (en) | 2018-09-11 | 2023-04-04 | Direct Digital Llc | Nutritional supplements and therapeutic compositions comprising probiotics |
Also Published As
Publication number | Publication date |
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CN1960739B (zh) | 2010-06-16 |
US20080268065A1 (en) | 2008-10-30 |
WO2005094849A1 (ja) | 2005-10-13 |
TW200533299A (en) | 2005-10-16 |
EP1741437A4 (en) | 2009-06-24 |
US8067034B2 (en) | 2011-11-29 |
CN1960739A (zh) | 2007-05-09 |
EP1741437A1 (en) | 2007-01-10 |
JP4891069B2 (ja) | 2012-03-07 |
JPWO2005094849A1 (ja) | 2008-02-14 |
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