JP2018043964A - Sleep improving composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide methods for improving a sleep state qualitatively, more specifically, methods for improving a hypnagogic situation, a sleep continuity, a mood at the time of getting up and after getting up (alleviation of negative mentation, such as a fatigue feeling, insecurity and/or embarrassment).SOLUTION: A sleep improving composition containing lactoferrin is provided. Preferably, at least some of the lactoferrin is involved in a liposome. The composition is provided as a pharmaceutical composition or a food composition.SELECTED DRAWING: None

Description

  The present invention relates to a composition for improving sleep that qualitatively improves a sleep state. More specifically, the present invention relates to a composition for improving sleep, which improves a sleep state, continuity of sleep, and mood when waking up (reduction of negative mental states such as fatigue, anxiety and embarrassment).

  Sleep is deeply related to mental and physical health, and when the mental and physical health deteriorates, the quality of sleep often deteriorates, and even when the quality of sleep deteriorates, the physical and mental health deteriorates. There are many. In particular, in recent social life, there are many opportunities to receive various strong stresses, and therefore, an increasing number of people suffer from a decrease in QOL due to sleep quality deterioration such as sleep disorders. On the other hand, as a means of improving sleep, if it is a morbid level, it is possible to consult a medical institution and receive use or counseling of a medicine such as a sleep inducer. However, there are many people who are not in a state of receiving treatment but feel unwell or often feel unwell and have troubles that cannot secure a simple and effective means.

  For this reason, various methods for improving sleep have been proposed. For example, a method of using a system that collects sleep information, lifestyle habit information and living situation information using a sensor and advises a method of qualitatively improving sleep by analyzing the data (Patent Document 1), bedding To improve by adding temperature control function (Patent Document 2), methods to improve by stimulating olfaction using aroma components (Patent Documents 3 and 4), orally ingesting ingredients contained in animals and plants (Patent Documents 5 to 7) and the like. However, these methods are not only difficult to achieve a sufficient effect and difficult to carry out on a continuous basis, but also cause health problems due to continuous oral intake of substances that are not derived from the human body at a higher concentration than normal intake. There was a problem that could cause.

Japanese Patent Laid-Open No. 2006-122347 Japanese Patent Laying-Open No. 2015-167639 JP 2014-196250 A Japanese Patent Laying-Open No. 2015-081227 JP 2006-153387 A JP-A-2015-199686 JP 2006-079096 A

  The present invention relates to a method for qualitatively improving a sleep state, more specifically, a state of sleep, continuity of sleep, and mood after waking up (reduction of negative mental state such as fatigue, anxiety, embarrassment) The issue is to provide a method for improvement.

  The present inventors improve the sleep state, sleep continuity, and mood at waking up (reduction of negative mental state such as fatigue, anxiety and embarrassment) by continuously ingesting lactoferrin. As a result, the present invention has been completed.

The invention encompasses, for example, the subject matter described in the following sections.
Item 1.
A composition for improving sleep comprising lactoferrin.
Item 2.
Item 2. The sleep improving composition according to Item 1, wherein a part of the lactoferrin is encapsulated in at least a liposome.
Item 3.
Item 3. The sleep improving composition according to Item 2, wherein a part of the lactoferrin is encapsulated in liposomes.
Item 4.
Item 4. The sleep improving composition according to any one of Items 1 to 3, which is a pharmaceutical composition or a food composition.

  According to the present invention, the sleep state is qualitatively improved by improving sleep state, continuity of sleep, and feeling when waking up (reduction of negative mental state such as feeling of fatigue, anxiety and embarrassment). In addition, QOL can be improved.

  Lactoferrin is an iron-binding glycoprotein having a molecular weight of about 80,000, and is present in mammalian milk, saliva, tears, semen, various mucus and the like. In humans as well, breast milk, especially colostrum, which is secreted a lot during the first few days after delivery, is found in large numbers, and is considered to play an important role in maintaining health such as acquiring immunity in newborns. In addition, lactoferrin is widely distributed in the body even after newborns. For example, it is contained in secretions such as saliva, tears, and duodenum, and is considered to play an important role for non-newborns. The lactoferrin used in the present invention is preferably extracted from milk in terms of cost, but the origin is not particularly limited. Further, it may be apolactoferrin, natural lactoferrin or hololactoferrin. Specifically, ion exchange from colostrum, transitional milk, normal milk, end milk, etc. of processed milk such as human, cow, buffalo, horse, goat, sheep, etc. Lactoferrin separated by conventional methods such as chromatography, apolactoferrin from which iron is removed from lactoferrin by conventional methods, metal-bound lactoferrin obtained by partially chelating a metal such as iron, copper, zinc, manganese, etc. Fully chelated metal saturated lactoferrin, etc. can be used. In particular, bovine or human derived lactoferrin is preferred. As commercially available products, for example, Morinaga lactoferrin MLF-EX (manufactured by Morinaga Milk Industry Co., Ltd.), “Bioferrin” (manufactured by Granbia Nutritionals), and “Lactoferrin” (manufactured by Fonterra) can be preferably used.

  The lactoferrin used in the present invention may be in the form of being encapsulated in liposomes (hereinafter sometimes referred to as “liposome containing lactoferrin” or “liposome encapsulating lactoferrin”). That is, a liposome containing lactoferrin can also be preferably used, and an embodiment in which a part of lactoferrin is encapsulated in the liposome is most preferable. The present invention also includes a composition for improving sleep, which includes a liposome containing lactoferrin as an active ingredient.

  Liposomes are lipid vesicles and are formed by hydrating lipids mainly composed of phospholipids with a sufficient amount of water. Generally, the classification is based on the number of lipid bilayers, and is classified into multilamellar liposomes (MLV) and single membrane liposomes. The unilamellar liposome is further classified into SUV (small unilamella vesicle), LUV (large unilamella vesicle), GUV (giant unilamella vesicle), etc. according to the size. Any of these may be sufficient as the liposome of this invention. Preferred is MLV. In the present invention, the size of the liposome is usually 30 to 1000 nm, preferably 30 to 600 nm, more preferably 50 to 200 nm.

  As the phospholipid, usually lecithin can be used. As lecithin, for example, egg yolk lecithin, soybean lecithin, rape lecithin, corn lecithin, sunflower lecithin, peanut lecithin and the like can be used alone or in combination of two or more. In the present invention, these hydrogenated products can also be used. Lecithin is also called phosphatidylcholine or 1,2-diacylglycerol 3-phosphocholine, and generally fatty acids are bound to the 1-position and 2-position of glycerol. In the present invention, it is preferable to use lecithin in which an unsaturated fatty acid having 12 to 24 carbon atoms is bonded to both or one of the 1st and 2nd positions in addition to the above exemplified lecithin. It is particularly preferable to use lecithin having a saturated fatty acid having ˜24 and an unsaturated fatty acid having 12 to 24 carbon atoms bonded to the 2-position. Here, the saturated fatty acid and the unsaturated fatty acid may be either linear or branched. As a preferable unsaturated fatty acid, an unsaturated fatty acid having 16 to 18 carbon atoms can be used. In particular, lecithin having a large amount of oleic acid and linoleic acid bonded to the 2-position is preferred. Specifically, egg yolk lecithin and soybean lecithin are preferable.

  Liposomes containing lactoferrin can be produced by conventional methods. For example, a desired amount of lecithin and, if necessary, a desired amount of sterol are solubilized with an appropriate organic solvent such as ethanol, and the solvent is removed under reduced pressure to form a membrane lipid. A liposome encapsulating lactoferrin can be obtained by adding an aqueous solution containing a physiologically active substance and stirring the mixture at about 1000 to 3000 rpm for about 2 to 5 minutes to prepare a liposome suspension.

  In addition to this method, a desired amount of lecithin and, if necessary, a desired amount of sterol are dissolved in a small amount of ethanol, dispersed in an aqueous solution or buffer solution, preliminarily emulsified, and then dispersed at high pressure. Liposomes encapsulating lactoferrin can also be obtained by preparing a liposome suspension by forming a multilayer.

  As sterols, sterols derived from animals such as cholesterol, lanosterol, dihydrolanosterol, desmosterol, dihydrocholesterol; plants such as β-sitosterol, campesterol, stigmasterol, brassicasterol, ergosterol, ergostadienol, sitosterol, and brassicasterol Sterols derived from (phytosterol); sterols derived from microorganisms such as timosterol and ergosterol, and the like, can be used alone or in combination of two or more. Among these, cholesterol or phytosterol is preferably used.

  The molar ratio of lecithin and sterol in the liposome is preferably about 55:45 to 95: 5, more preferably about 60:40 to 90:10, and most preferably about 75:25 to 85:15. When the molar ratio is within these ranges, the stability of the liposome membrane is improved. The content of lecithin or sterol can be measured by a known method. For example, the lecithin content can be quantified by the Fiske-Subbarow method, and the sterol content can be quantified by HPLC, a colorimetric method, or the like.

  In the liposome encapsulating lactoferrin used in the present invention, lactoferrin is preferably enclosed in a space surrounded by the liposome membrane, but lactoferrin may be included as a liposome membrane constituent, or multilamellar liposomes May be contained between the multiple membranes constituting the membrane, or may be contained in a form in which lactoferrin adheres to or binds to the outermost membrane of the liposome membrane.

  If necessary, the suspension of the liposome encapsulating the lactoferrin may be subjected to an operation for removing the lactoferrin in the liposome outer liquid, for example, an operation for dialyzing the obtained filtrate after filtering the suspension. Good. The liposome suspension can be used in a liquid state, but can also be used as a lyophilized dry product. Liposomes can be in a form suitable for various oral intakes, including those obtained by tableting or encapsulating the dried product.

  The contents of lactoferrin, lecithin and sterol in the suspension of liposomes encapsulating lactoferrin are as follows. The content of lactoferrin is preferably about 10 to 99% by mass, more preferably about 20 to 95% by mass, and still more preferably about 30 to 90% by mass. The content of lecithin is preferably about 1 to 80% by mass, more preferably about 3 to 65% by mass, and still more preferably about 5 to 50% by mass. The sterol content is preferably about 0 to 40% by mass, more preferably about 0.1 to 30% by mass, and still more preferably about 1 to 20% by mass. Further, if the content of lactoferrin is up to about 3 times the content of lecithin, all of the lactoferrin may be encapsulated in the liposome, but if it exceeds 4 times, at least a part of the lactoferrin is contained in the liposome. It is present in the suspension in an unencapsulated form.

  Furthermore, the surface of the liposome containing lactoferrin can be coated, and this coating can also be used as an active ingredient. A preferable coating includes a coating with a polysaccharide containing a sulfate group. Examples of sulfate group-containing polysaccharides include fucoidan, carrageenan, agar, and heparin. The sulfate group-containing polysaccharide includes a sulfated polysaccharide that does not contain a sulfate group, and may be chondroitin sulfate, dermatan sulfate, or the like.

  As the sulfate group-containing polysaccharide, those having a molecular weight of about 5000 to 300000 are preferably used. Among these sulfate group-containing polysaccharides, fucoidan and carrageenan can be preferably used, and fucoidan is particularly preferable. About 10-500 mass parts is preferable with respect to 100 mass parts of lecithin contained in a liposome, for example, and the usage-amount of a sulfate group containing polysaccharide is more preferable about 20-200 mass parts.

  Coating can be performed, for example, by adding a sulfate group-containing polysaccharide to a suspension containing liposomes containing lactoferrin and stirring at about 1000 to 3000 rpm for about 2 to 5 minutes. A plurality of liposomes may be contained in one coating film. In addition, it can confirm that the liposome is coated with the sulfate group-containing polysaccharide, for example, by changing the zeta potential of the liposome solution when the sulfate group-containing polysaccharide is added and stirred.

  The sleep-improving composition containing lactoferrin according to the present invention realizes “high quality sleep” in which sleep and sleep are sufficiently obtained, making it difficult to feel sleepiness when waking up, It is possible to obtain an effect that makes it difficult to have a negative thinking tendency.

  The content of lactoferrin in the composition for improving sleep containing the lactoferrin is not particularly limited as long as the effect of the present invention is achieved. For example, about 1 to 10000 mg, 5 to 5000 mg, 10 to 2000 mg, or 20 to 1000 mg can be exemplified. Also, the content ratio is not particularly limited, and examples thereof include about 0.1 to 100% by mass, 1 to 99% by mass, or about 10 to 80% by mass. Furthermore, the amount of lactoferrin ingested when the composition for improving sleep is also not particularly limited, and examples thereof include about 10 to 10,000 mg, 20 to 5000 mg, 30 to 2000 mg, or about 50 to 1000 mg per day for an adult. .

  The composition for improving sleep containing the lactoferrin is preferably taken once or a plurality of times (preferably 2-3 times) per day for an adult. In the case of a child, it is preferable to limit the number of times of intake or limit the amount of intake per time according to age. Examples of the restriction method include a method of reducing the number of ingested places in the case of an adult, a method of taking a dividing line according to the amount of intake after providing a dividing line on a tablet or tablet. The subject to which the intake is applied is preferably a human, but may be a non-human mammal other than a human. Even if the subject of application is a non-human mammal (eg, pet or livestock, more specifically, dog, cat, monkey, cow, pig, sheep, etc.), the administration or intake of the human should be set as appropriate. Can do.

  The sleep improving composition containing the lactoferrin can be preferably used as a pharmaceutical composition, a quasi-drug composition, or a food composition (including a beverage composition and a food additive composition).

  When used as a pharmaceutical composition or quasi-drug, the other ingredients include pharmaceutically acceptable bases, carriers, and / or additives (eg, solvents, dispersants, emulsifiers, buffers, stabilizers, stabilizers, Examples thereof include a shape agent, a binder, a disintegrant, and a lubricant. The form of the pharmaceutical composition is not particularly limited, and examples thereof include tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules and the like. These forms of pharmaceutical preparations can be prepared by a conventional method by combining the other components and lactoferrin as necessary.

  When used as a food composition, examples of other components include bases, carriers, additives, and other components and materials that can be used as food. In addition, the form of the food composition is not particularly limited, and examples thereof include health functional foods such as foods for specified health use, nutritional functional foods, functional labeling foods; foods for sick people, breast milk for pregnant women, infant formulas, infant formulas Special foods such as: Nutritional supplements, health supplements, nutritionally adjusted foods, so-called health foods such as supplements; cooked foods for the sick (hospital foods, sick foods, nursing foods, etc.) These can be prepared by conventional methods. In particular, functional health foods such as foods for specified health use, functional nutritional foods, functional labeling foods; special-purpose foods such as sick foods, breast milk for pregnant women, infant formula, infant formulas; nutritional supplements, health supplements, When preparing a food composition as a so-called health food such as a nutritionally adjusted food or a supplement, for example, granules, capsules, tablets (including chewables), beverages (beverage powder) , Drinks, etc.) are preferred, and capsules, tablets, tablets, beverage powders, drinks are preferred from the viewpoint of ease of ingestion, but are not particularly limited to these. Absent. When used as a food additive composition among food compositions, examples of the form include liquid, powder, flake, granule, and paste.

  Although not particularly limited, particularly preferable examples of the other components of the sleep improving composition containing lactoferrin include dextrin, cellulose, lecithin (particularly derived from soybeans), fine silicon dioxide, calcium stearate and the like.

  In this specification, “including” includes “consisting essentially of” and “consisting of” (The term “comprising” includes “consisting essentially of” and “consisting of.”).

Hereinafter, the present invention will be specifically described, but the present invention is not limited to the following examples.
Morinaga lactoferrin MLF-EX (manufactured by Morinaga Milk Industry Co., Ltd.) was used as a test composition for examining the influence of lactoferrin on the sleep state . MLF-EX is a food material containing 90% or more of bovine-derived LF, which is an existing natural food additive. In addition to MLF-EX, dextrin, cellulose, lecithin (derived from soybean), fine silicon dioxide, and calcium stearate were blended and compressed to produce tablets (300 mg). At the time of manufacture, the amount of raw materials was adjusted to contain 270 mg as LF per 6 tablets (that is, 45 mg of lactoferrin contained per 300 mg of tablets). Moreover, the tablet which replaced MLF-EX with dextrin was similarly manufactured as a placebo. Subjects took 6 tablets each day for 4 weeks. When waking up in the morning, all days from 2 weeks before the start of the test to 3 days before the start of the test, 3 days immediately after the start of the test, 3 days immediately before the 2nd week, and 3 days from the 2nd week to the 4th week after the start of the test A questionnaire survey using the OSA sleep survey MA version (OSA sleep inventory MA version) (Japan Sleep Improvement Council public version) was conducted. OSA sleep survey MA version includes the following factors: Factor 1: sleepiness on rising, Factor 2: initialization and maintenance of sleep, Factor 3: frequent dreaming, Factor 4 : Fatigue recovery (refreshing), Fifth factor: Sleep factor (sleep length), 16-item question (4 step evaluation. Negative evaluation is “1” to positive evaluation is “4”. For example, in the first question , "1" Very tired. "2" Somewhat tired. "3" Somewhat tired. "4" Very tired.) It was conducted for the purpose of investigating the psychology and physical condition of each factor from the answer results of 16 questions. In addition, the Japanese version of the POMS shortened version for adults (Profile of Mood States-Brief Form Japanese Version) (Co) A questionnaire survey using Kaneko Shobo) was conducted to evaluate state checks such as mood and fatigue. The Japanese version of the shortened version of POMS has 35 questions (five-level evaluation. For example, in the first question, “People have fun,” there was no “0”. “1” was a little “2” was OK "3" was pretty much "4" was very much), and using a dedicated tool, 7 scales such as (confused-embarrassed) (tension-anxiety) and negative mood states comprehensively (TMD score) is expressed, and it is known that these scales and scores are more negative as the numerical value is higher. The obtained results are shown in Table 1. The fluctuation value means a numerical value obtained by subtracting the evaluation point at the start of the test from each evaluation point after the start of the test. The TMD score (Total Mood Disturbance) is a score that comprehensively represents a negative mood state.

As shown in Table 1, the lactoferrin drinking group (LLF) improved in feeling of sleepiness when waking up, ease of falling asleep and maintaining sleep state, and feeling of recovery from fatigue when waking up. I showed the result of preventing becoming. On the other hand, in the placebo group, the results showed that the patient was aggravated by the feeling of sleepiness and recovery from fatigue when waking up, and tended to fall into a negative mental state. The period of this study was from the end of March to the beginning of June, but this period is a transition between the winter season when the sympathetic nerves are relatively strong and the summer season when the parasympathetic nerves are relatively strong. It is known that physical condition and mental state are most likely to be bad throughout the year. Especially in the mental state, it falls into a negative mental state in spring, seasonal emotional disorder and depressive symptoms occur even in healthy people, and there are many people who develop and relapse depression in those who have a mental history. Is also known. The temperature and humidity at the time of this test varied in the range of 6.5 ° C., 58 RH% to 19.8 ° C., 72 RH% in the measurement data of the Japan Meteorological Agency (Osaka Prefecture). The fact that the placebo group's results in this study showed a tendency to fall into sleep state and negative mental state is thought to be due to seasonal factors. Therefore, it can be inferred that the test result of the lactoferrin drinking group shows that there is an effect of improving the sleep state and improving from the negative mental state to the positive mental state, similarly considering the seasonal factors.

Claims (4)

A composition for improving sleep comprising lactoferrin. The composition for improving sleep according to claim 1, wherein a part of the lactoferrin is encapsulated in at least a liposome. The composition for improving sleep according to claim 2, wherein a part of lactoferrin is encapsulated in liposomes. Item 4. The sleep improving composition according to any one of Items 1 to 3, which is a pharmaceutical composition or a food composition.