WO2014175119A1 - エネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防剤、または方法 - Google Patents
エネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防剤、または方法 Download PDFInfo
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Definitions
- the present invention relates to the use of D-psicose to improve energy metabolism. More particularly, the present invention relates to the use of D-psicose and / or its derivatives for promoting energy consumption and / or treating and / or preventing reduced energy consumption function.
- Energy metabolism refers to the input / output and conversion of energy related to biological activities such as the process of decomposing and absorbing nutrients and producing adenosine triphosphate (ATP).
- Energy metabolism is often reduced or worsened in mammals, including humans, particularly older mammals, menopausal mammals, or mammals with health or other problems that cause a decrease in energy metabolism.
- Such mammals have a reduced heat production function and a low basal metabolism, so that the amount of energy consumed tends to be lower than the amount of energy consumed.
- the ingested nutrients cannot be completely converted into combustion energy using heat production, but are partially converted into fat and accumulated in fat cells.
- adaptive reduction in heat production is likely to occur, for example, within or after a diet that reduces weight.
- US Pat. No. 6,057,049 includes isoflavones that have not been previously known to affect energy metabolism, preferably in animals in amounts of about 0.001 to about 10 g / kg / day.
- Patent Document 2 discloses an energy consumption promoter containing chlorogenic acids or salts thereof as an active ingredient
- Patent Document 3 discloses an energy consumption promoter containing rice bran extract as an active ingredient, which is highly safe.
- Patent Document 4 discloses a nutritional composition comprising a Garcinia Cambodian extract, a Gymnema sylvestre leaf extract, and a green tea leaf extract, and the intake of the nutritional composition promotes rapid weight loss in an individual, A method is proposed that burns, increases heat production, assists energy metabolism and / or suppresses appetite.
- Patent Document 5 discloses a hypoglycemic agent, an antidiabetic agent, a chemokine MCP-1 secretion inhibitor, an anti-arteriosclerosis agent, and a microglia migration inhibitor, which contains D-psicose as an active ingredient.
- a bioactive agent selected from the group consisting of an anti-ischemic cerebral nervous system disease agent is disclosed in Patent Document 6 as D-psicose, or substantia nigra dopaminergic activity containing D-psicose and D-allose as active ingredients.
- Patent Document 7 An inhibitor of nerve cell oxidative damage is disclosed in Patent Document 7, which includes D-psicose and / or its derivative as an active ingredient, and rapid blood glucose caused by D-glucose constituting digestible sugar ingested by food and beverages.
- Abnormal plasma glucose levels throughout the day for mammals that need to suppress increases in levels and suppress abnormal increases in plasma glucose levels throughout the day Disclosed is a composition for suppressing an abnormal increase in plasma glucose concentration, which is a composition for ingesting D-psicose and / or a derivative thereof on a regular basis for at least 7 weeks in order to suppress the increase .
- D-psicose such as hypoglycemia, inhibition of chemokine MCP-1 secretion, and inhibition of microglia migration have been elucidated to some extent.
- D-psicose and its derivatives used for heat production stimulation according to the present invention are generated by a surprisingly different action profile, and furthermore, there is no indication of a heat production promoting action. It has not been clarified as to whether it is effective with only the intake.
- An object of the present invention is to provide a solution using a functional food called a rare sugar containing at least D-psicose that effectively improves energy metabolism.
- a drug that can effectively treat and prevent diseases that require correction of basal metabolism decline, hypothermia, obesity suppression, visceral fat accumulation suppression, hyperglycemia, hyperlipidemia, and muscle mass reduction is an urgent need for the development of health foods and drinks or animal feeds that can treat and / or prevent reduced consumption function.
- the object of the present invention is to solve the above-mentioned problems by promoting energy consumption and / or food and drink for treatment and / or prevention of reduced energy consumption function, feed, pharmaceuticals, quasi drugs, oral compositions, cosmetics, Another object of the present invention is to provide an additive for foods and drinks that has an effect of promoting energy consumption and / or treating and / or preventing a decrease in energy consumption function.
- the present inventors have found that D-psicose, which has not been known as an effect of rare sugars, improves energy metabolism, specifically, D- I found that the consumption of psicose increases the energy consumption calculated from breathing at rest, and that D-psicose takes 2.5 g or more per day for 2 weeks, “feeling that my body is warm”
- the present invention comprises the following therapeutic and / or preventive agents for promoting energy consumption and / or reducing energy consumption function.
- the first invention is a therapeutic and / or preventive agent for promoting energy consumption and / or reducing energy consumption function, comprising D-psicose as an active ingredient.
- the therapeutic and / or preventive agent for promoting energy consumption and / or reducing energy consumption function is a food, beverage, feed, pharmaceutical, quasi-drug, oral composition, cosmetic. Or food and beverage, food, feed, pharmaceuticals, quasi-drugs, oral compositions, cosmetics, or food and drink so that D-psicose is 2.5 g or more on an adult basis. It is for ingestion in the form of a pharmaceutical additive.
- the therapeutic and / or preventive agent for promoting energy consumption and / or reducing the function of energy consumption has a D-psicose of 2.5 g or more on an adult basis. It is intended for continuous ingestion at least once a day.
- a fourth invention is characterized in that, in any one of the first to third inventions, D-psicose contained by subjecting glucose, fructose and / or isomerized sugar to alkali isomerization is used as an active ingredient.
- D-psicose in any one of the first to fourth inventions, D-psicose is D-psicose and / or a derivative thereof, the derivative of D-psicose is a ketone group of D-psicose It is characterized by being a D-psicose derivative selected from a sugar alcohol as a base, uronic acid in which the alcohol group of D-psicose is oxidized, and an amino sugar in which the alcohol group of D-psicose is substituted with NH 2 group.
- a sixth invention is characterized in that, in any one of the first to fifth inventions, D-psicose is to be taken at a daily dose of 2.5 g to 25 g together with a meal for at least two weeks on an adult basis.
- a seventh aspect of the invention is directed to any one of the first to sixth aspects of the invention for ingestion by mammals including humans in need of promotion of energy consumption and / or treatment and / or prevention of reduced energy consumption function. It is characterized by being.
- the present invention comprises the following methods for promoting energy consumption and / or treating and / or preventing energy consumption function deterioration.
- the eighth invention is a method for promoting and / or preventing energy consumption and / or reducing energy consumption function, comprising the step of administering the therapeutic and / or prophylactic agent of any one of the first to seventh inventions to a subject. is there.
- the present invention can provide a solution using a functional food called a rare sugar containing at least D-psicose that effectively improves energy metabolism.
- the therapeutic and / or preventive agent for promoting energy consumption and / or reducing energy consumption function of the present invention is a food / beverage product, feed, pharmaceutical product, quasi-drug, oral composition, cosmetic product, or food / beverage product additive.
- a composition food, food, feed, pharmaceutical, quasi-drug, oral composition, cosmetic, or food-and-food additive
- It is also effective in preventing and / or improving energy consumption and preventing and / or improving basal body temperature.
- the nutritional composition of the present invention can be used over a long period of time without applying excessive protein load even to elderly people who are highly safe and whose renal function is attenuated.
- mammals including humans in need of prevention and treatment of diseases requiring reduction of basal metabolism, hypothermia, obesity suppression, visceral fat accumulation suppression, hyperglycemia, hyperlipidemia, and muscle mass reduction
- a composition for ingestion by a mammal can be provided.
- each value is an energy metabolism value obtained by dividing the average value every 12 minutes by the weight of the rat.
- the results of energy metabolism measurement of rats by long-term administration of D-psicose which is an example, are energy metabolism values obtained by dividing the values of the light period state and the dark period state at 5 to 7 weeks of administration by the rat weight at the time of measurement.
- each value is energy consumption (REE), carbohydrate combustion amount (CEE) and lipid combustion amount (FEE) from 20 minutes to 4 hours after breakfast intake. Is the energy metabolism value divided by body weight.
- the energy consumption as used in the present invention is basic metabolism that is energy consumption for maintaining life such as respiration and body temperature regulation, life metabolism that is energy consumption by exercise and work, energy consumption that is induced when food is ingested. Some diet-induced heat metabolism. The portion of the ingested energy source that is not consumed is accumulated in the body as fat. Fat accumulation as a certain energy source is necessary, but excessive accumulation is not preferable because various diseases are easily caused. Therefore, it is preferable that the energy consumption such as basal metabolism is high.
- D-psicose as used in the present invention is a kind of rare sugar, and is produced enzymatically or chemically from D-fructose (fructose) or indirectly from D-glucose (glucose) by epimerization, Alternatively, it may be extracted from a plant and completely purified, or may contain impurities contained in a small amount when produced. For example, it is relatively easily prepared by an enzymatic method using epimerase as described in Patent Document 8. Moreover, what was manufactured chemically as described in a nonpatent literature 1 may be used.
- the D-psicose solution obtained as described above can be purified by a method such as deproteinization, decolorization, desalting, etc., if necessary, and concentrated to collect a syrup-shaped D-psicose product. 99% or more highly pure powder products can also be obtained by fractionation and purification by chromatography. Such D-psicose can be used as it is as a monosaccharide.
- Rare sugars as used in the present invention are simple sugars that exist only in trace amounts in nature compared to “natural monosaccharides” represented by D-glucose, which is abundant in nature, among simple sugars that are basic units of sugar. It is defined as sugar (aldose, ketose) and its derivatives (sugar alcohol). In general, there are six types of aldoses present in large quantities in nature: D-glucose, D-galactose, D-mannose, D-ribose, D-xylose and L-arabinose, and the other aldoses are defined as rare sugars. In addition, as ketose, D-fructose is relatively abundant in nature, but other ketoses can be said to be rare sugars.
- rare ketose sugars examples include D-psicose, D-tagatose, D-sorbose, L-fructose, L-psicose, L-tagatose, and L-sorbose.
- Sugar alcohols can be produced by reducing monosaccharides, but in nature there are relatively many D-sorbitols, but the others are quantitatively small, so these are also rare sugars.
- D-psicose and D-allose are currently rare sugars that can be mass-produced.
- D-psicose is classified as a hexose ketose
- D-allose is classified as a hexose aldose.
- D-psicose can be obtained by any means including those extracted from nature, those synthesized by chemical or biological methods, and the like.
- D-allose can be obtained by causing D-xylose isomerase to act on a solution containing D-psicose to produce D-allose from D-psicose by an enzymatic method (Patent Document 9).
- D-psicose in the present invention can also be used as a syrup containing isomerized sugar, instead of being used as the above-mentioned powder product.
- This syrup can be easily obtained as a commercial product “Rare Sugar Sweet” (release source: Rare Sweet Co., Ltd., seller: Matsutani Chemical Industry Co., Ltd.).
- “Rare Sugar Sweet” is a syrup containing rare sugars obtained from the isomerized sugar as a raw material and obtained by the technique disclosed in Patent Document 10, and the rare sugars mainly contain D-psicose and D-allose. Is manufactured.
- the rare sugars contained in the rare sugar-containing syrup obtained by this method are 0.5 to 17% by mass of D-psicose and 0.2 to 10% by mass of D-allose in proportion to the total sugars. Sugar is also included.
- the method for obtaining a rare sugar-containing syrup is not limited to the above-described method, but a reaction discovered in the latter half of the 19th century by reacting an alkali with a monosaccharide (D-glucose or D-fructose), Robry de Bruin-Fan et al.
- a syrup obtained by alkaline isomerization from D-glucose and / or D-fructose as a raw material until the D-glucose and / or D-fructose content is 55 to 99% by mass is mainly used.
- a method for separating and measuring by high performance liquid chromatography is common, and examples of the measurement conditions include the measurement conditions described in Patent Document 9 (detector; RI, column) Mitsubishi Chemical Co., Ltd. MCI GEL CK 08EC, column temperature; 80 ° C., mobile phase; purified water, mobile phase flow rate: 0.4 mL / min, sample injection amount: 10 ⁇ L).
- Examples of raw materials used for the production of the rare sugar-containing syrup include starch, sugar, isomerized sugar, fructose, glucose and the like.
- Isomerized sugar is widely regarded as a mixed sugar mainly composed of D-glucose and D-fructose in a specific composition ratio, and is generally obtained by hydrolyzing starch with an enzyme such as amylase or an acid.
- it refers to a liquid sugar mainly composed of glucose and fructose obtained by isomerizing a sugar solution mainly composed of glucose with glucose isomerase or alkali.
- fructose fructose liquid sugar has a fructose content (ratio of fructose in sugar) of less than 50%
- fructose dextrose liquid sugar has 50% or more and less than 90%
- 90% or more Is called “high fructose liquid sugar”
- glucose fructose liquid sugar added with a quantity of sugar not exceeding glucose fructose liquid sugar is called “sugar mixed fructose glucose liquid sugar”.
- the rare sugar-containing syrup of the present invention Any isomerized sugar may be used as the raw material.
- a rare sugar-containing syrup made of D-fructose as a raw material contains 5.2% D-psicose, 1.8% D-allose, 15.0% glucose, and 69.3% D-fructose.
- the rare sugar-containing syrup made from isomerized sugar contains 3.7% D-psicose, 1.5% D-allose, 45.9% glucose, 37.7% D-fructose, and D-glucose.
- As a raw material it contains 5.7% D-psicose, 2.7% D-allose, 47.4% glucose, and 32.1% D-fructose. Will change.
- D-psicose used in the present invention can be used as D-psicose and / or a derivative thereof.
- a derivative is a name for a compound obtained by converting the structure of a molecule from a certain starting compound by a chemical reaction.
- sugar alcohols and amino sugars are derivatives.
- D-psicose a sugar alcohol in which the ketone group is an alcohol group, uronic acid in which the alcohol group is oxidized, and an amino sugar in which the alcohol group is substituted with an NH 2 group are derivatives of D-psicose.
- the specificity for the enzyme is the main cause of the action mechanism, and the three-dimensional structure of the sugar is particularly important.
- an enzyme called fructokinase in the liver phosphorylates fructose as a main substrate.
- D-tagatose and D-psicose, which are isomers at the C-3 position of fructose, are also phosphorylated by this enzyme, and it is known that the phosphorylation rate varies depending on the respective three-dimensional structure (Non-patent Document 2). ).
- the reaction rate is particularly affected depending on whether the carbon at the 2, 3, 4, 5 position is trans or axial. Therefore, even if it is a derivative
- the D-psicose used in the present invention may be used as a mixed sugar mixed with a mixed sugar such as D-glucose, D-fructose or other rare sugar (such as allose).
- a mixed sugar such as D-glucose, D-fructose or other rare sugar (such as allose).
- D-psicose and its derivatives have an effect of promoting energy consumption in humans and relatively large mammals by continuous ingestion.
- D-psicose and its derivatives are continuously ingested at least once a day so that the adult standard is 2.5 g or more as D-psicose.
- the daily dose is in the range of 2.5 g to 25 g, preferably 2.5 g to 20 g on an adult basis, divided into once a day or two or three times a day at an appropriate interval, It may be taken before meals, after meals or with meals. If the intake amount is less than 2.5 g, the effect is not expressed, and if it is more than 25 g, the daily cost becomes too high, which is not preferable. It can be determined in consideration of how much the biological metabolic parameters should be reduced, whether the body weight is within the range of the standard body weight, and the like.
- the intake of D-psicose and its derivatives can be increased by ingesting before, after or with meals compared to the case of not ingesting energy consumption immediately after ingestion. Moreover, the energy consumption promotion effect becomes more preferable by ingesting continuously.
- the preferred continuous intake period is 2 weeks or longer.
- D-psicose and its derivative as used in the present invention may be any form such as powder, fine powder, granule, crystal, solid substance such as tablet, aqueous solution, solution and the like.
- this production method is not particularly limited.
- the present invention provides a food / beverage product, a feed, a pharmaceutical product, a quasi-drug, an oral composition characterized by using a material having a particular functionality, including the composition containing the D-psicose.
- Cosmetics and food additives That is, it is added to foods, drinks, feeds, pharmaceuticals, quasi drugs, oral compositions, cosmetics, or food and drink additives, and D-psicose is 2.5 g or more per unit on an adult basis. As such, it is for ingestion in the form of food and drink, feed, pharmaceuticals, oral cavity composition, or food and drink additive.
- the foods and drinks in the present invention include, for example, soy sauce, powdered soy sauce, miso, powdered miso, moromi, horsetail, fried potatoes, mayonnaise, dressing, vinegar, three cups of vinegar, Chinese sushi vinegar, Chinese food, tentsuyu, noodle soup, sauce, ketchup
- a sweetener for various seasonings such as sauces for grilled meat, curry roux, stew ingredients, soup ingredients, dashi ingredients, compound seasonings, mirin, new mirin, table sugar, coffee sugar, and taste improvers, It can be advantageously used as a quality improver.
- various Japanese sweets such as rice crackers, hail, rice cakes, rice cakes, manju, eel, chanterelles, sheep mushrooms, water sheep rice cakes, brocade balls, jelly, castella, rice balls, bread, biscuits, crackers, cookies, pie, pudding , Butter cream, custard cream, cream puff, waffle, sponge cake, donut, chocolate, chewing gum, caramel, candy, etc.
- Paste such as paste, peanut paste, fruit paste, fruit such as jam, marmalade, syrup pickles, confectionery, processed foods such as vegetables, breads, noodles, cooked rice such as cooked meat, artificial meat, Fukujin pickled, lettuce pickled , Senzuke, Lucky pickles, etc.
- the above food and drink can also be used as functional foods, nutritional supplements or health foods.
- the form is not particularly limited.
- milk proteins with high amino acid balance, soy protein, protein such as egg albumin, degradation products thereof, egg white oligo In addition to peptides, soybean hydrolysates, and the like, mixtures of amino acids alone can be used according to conventional methods. It can also be used in the form of a soft capsule, a tablet or the like.
- Examples of functional foods or dietary supplements include liquid foods that contain sugars, fats, trace elements, vitamins, agents, fragrances, semi-digested nutritional foods, ingredient nutritional foods, drinks, capsules, Examples of processing forms such as enteral nutrients.
- foods and drinks such as sports drinks and energy drinks are further supplemented with nutritional additives and compositions such as amino acids, vitamins and minerals, spices and flavors to improve nutritional balance and flavor. , Pigments and the like can also be blended.
- the composition of the present invention When used for food, it can be prepared as it is, in a form diluted with oil, a milk form meal, or a form to which a carrier generally used in the food industry is added. Also good.
- the form of the beverage is a non-alcoholic beverage or an alcoholic beverage.
- Non-alcoholic drinks include, for example, non-carbonated drinks such as carbonated drinks, fruit juice drinks, and nectar drinks, soft drinks, sports drinks, tea, coffee, cocoa, etc.
- the form of general foods, such as plum wine, beer, happoshu, and 3rd beer, can be mentioned.
- the use form of the composition of the present invention as a food material or food additive for the purpose of improving the biological action includes solid preparations such as tablets or capsules, powders or granules dissolved in beverages, semi-forms such as jelly, etc. There are solids, liquids such as drinking water, and high-concentration solutions that are diluted. Furthermore, the composition of the present invention can be appropriately added to foods to provide health foods or sick foods for the purpose of improving biological functions. As optional components, vitamins, carbohydrates, pigments, fragrances and the like that are usually added to foods can be appropriately blended.
- the food can be eaten in any form, liquid or solid. It can be eaten as a soft capsule encapsulated by gelatin or the like.
- the capsule is made of a gelatin film prepared by adding water to raw material gelatin and dissolving it, and adding a plasticizer (glycerin, D-sorbitol, etc.) thereto.
- the composition of the present invention can be applied to feed for livestock, poultry and pets.
- livestock feeds such as dry dog food, dry cat food, wet dog food, wet cat food, semi-moist dock food, poultry feed, cattle, and pigs.
- livestock feeds such as dry dog food, dry cat food, wet dog food, wet cat food, semi-moist dock food, poultry feed, cattle, and pigs.
- the feed itself can be prepared according to a conventional method.
- These therapeutic agents and prophylactic agents include non-human animals, for example, domestic mammals such as cattle, horses, pigs and sheep, poultry such as chickens, quails and ostriches, pets such as reptiles, birds and small mammals, It can also be used for farmed fish.
- Drugs that make use of the effects of the composition of the present invention can be used alone, or can be mixed with appropriate additives such as general excipients, stabilizers, preservatives, binders, disintegrants, and liquids, granules Drugs, fine granules, powders, tablets, capsules, pills, ointments, patches, sprays, sprays, injections, etc. It can be administered dermally or intravenously.
- the composition of the present invention comprises a pharmaceutical organic or inorganic solid, semi-solid or liquid carrier, solubilizer or diluent suitable for oral, nasal, transdermal or intravenous administration.
- the composition can be used as a medicament.
- patients who are inadequately ingested they can be fed directly to the intestine or stomach using an administration tube, and can be ingested as a food or drink if they can be ingested.
- All water, gelatin, lactose, starch, magnesium stearate, talc, animal and vegetable oils, benzyl alcohol, gum, polyalkylene glycol, petroleum resin, coconut oil, lanolin, or other carriers used in medicine are all It can be used as a carrier for a medicament containing the composition of the invention.
- stabilizers, wetting agents, emulsifiers, and salts for changing the osmotic pressure or maintaining an appropriate pH of the compounding agent can be appropriately used as auxiliary agents.
- soluble films have been used for the formulation of cosmetics and the like.
- an edible soluble film is used as a flavor film retaining a fragrance or the like for the purpose of mood change, prevention of bad breath, and the like.
- the idea of using a cosmetic film holding a moisturizer or the like as a pack, or dissolving it in water and using it as an emulsion has been presented.
- an anti-inflammatory agent or the like as a poultice.
- a packaging material for foods and pharmaceuticals and as a carrier for holding active ingredients such as foods and pharmaceuticals, a soluble film that exhibits excellent solubility and film properties and can be suitably used for these applications has been proposed. (Patent Document 11)
- the composition of the present invention can be applied to pharmaceuticals, quasi drugs, and cosmetics.
- the decrease in basal metabolism in the elderly is mainly due to a decrease in the amount of muscle that has generated a lot of body heat, triggered by a decrease in protein synthesis ability with aging.
- the resulting decrease in basal metabolism may lead to anorexia and cause a vicious cycle that further reduces protein synthesis ability because nutrients cannot be sufficiently consumed.
- the composition of the present invention is useful for preventing and / or improving the reduction in basic energy consumption as described above.
- composition of the present invention is useful for preventing and / or improving the decrease in basal body temperature as described above.
- Obesity refers to a condition in which adipose tissue has accumulated excessively.
- Adipose tissue has an energy supply function, a heat insulating action for maintaining body temperature, a visceral protective action, and the like, and is appropriately required.
- excessive accumulation of fat tends to cause various health problems.
- visceral fat excessively attached around the viscera is considered to be a cause of the onset of diabetes, cerebral infarction, myocardial infarction, etc. and needs attention. Since obese people often have an increase in blood pressure and / or heart problems, a drug that improves heat production energy consumption and does not increase blood pressure is particularly advantageous.
- the composition of the present invention is useful for preventing and / or improving obesity and visceral fat accumulation as described above.
- adiponectin adiponectin from visceral fat decreases.
- adiponectin the action of insulin is lowered, so that the ability of glucose to be taken into cells from the blood is lowered, resulting in a state where the amount of glucose in the blood is high (hyperglycemia).
- Hyperglycemia is said to be accompanied by various complications such as diabetes, kidney damage, nerve damage, and myocardial damage.
- the nutritional composition according to the present invention is useful for the prevention and / or improvement of hyperglycemia associated with increased visceral fat as described above.
- the composition of the present invention can effectively suppress the onset of lipid metabolism abnormalities such as an increase in blood LDL cholesterol associated with increased visceral fat, and is useful for the prevention and / or improvement of lipid metabolism abnormalities associated with increased visceral fat. is there.
- muscle mass tends to decrease with aging.
- Ingestion of the composition of the present invention improves basal metabolism, stimulates appetite, and increases the intake of protein as a muscle source.
- it is particularly effective when the visceral fat that is deeply involved in abnormal lipid metabolism, hyperglycemia, fatty liver and liver function decline is used as an energy source for the synthesis of muscle proteins.
- the composition of the present invention greatly contributes to people such as elderly people and bedridden persons who have not had an effective health food or drink composition so far.
- the composition of the present invention is preferably used for increasing the muscle mass and / or suppressing the decrease in muscle mass of a person with reduced muscle mass (for example, an elderly person, bedridden person, etc.).
- the dose to be used of D-psicose and its derivatives will vary from one individual to another and of course may vary depending on the condition to be treated and the type of application.
- the daily dose for the treatment of inhibited and / or undesirably reduced heat production is given as a guide for adults as a D-psicose at least once a day in the range of 2.5 g to 30 g. It is preferably administered once a day, or divided into 2 or 3 times a day at an appropriate interval, or at a dose of 30 g or less per day before, after or with a meal. It is desirable to formulate D-psicose so that the unit dosage is 2.5 g or more. If the intake is less than 2.5 g, the effect is not expressed, and if it is more than 30 g, diarrhea is easily induced, which is not preferable.
- one is a glucose + fructose administration group ( ⁇ Psi group)
- one is a glucose + fructose + psicose administration group (+ Psi group)
- the other is an administration group in which only water is ingested (water administration) Group).
- rats were placed in cages of the respiratory metabolism measurement system for small animals MK-5000 (Muromachi Kikai Co., Ltd.) one by one, and indirect calorimetry and habituation started. It was. The light was turned on at 10 o'clock the next morning to enter the light state.
- each rat is weighed and acclimated for 3 hours, then the + Psi group contains a dose containing psicose and the -Psi group contains a dose not containing psicose at 5 ml / (300 g body weight).
- each rat was forcibly orally administered with a sonde.
- Table 1 shows the dosage, but the solution concentration is varied to match the total energy.
- only water was ingested in the water administration group. Thereafter, only pure water was allowed to be ingested, and the calorific value was continuously measured until 10:00 on the next day at 23 ° C. and in the light period.
- Resting energy exposure (hereinafter referred to as REE: kcal / min) was calculated by dividing the body weight (hereinafter referred to as BW; kg) using the Weir equation.
- BW body weight
- the average of the measured values from 12 minutes before to 60 minutes before the administration was taken as the value of 0 hour, and after calculating the amount of change from that, the value was averaged every 12 minutes for each rat.
- the value of the rat of the same group was averaged, and the average value of the data of the water administration group was subtracted from the data of the + Psi group (or Psi group) in each time zone, and expressed as ⁇ REE / BW.
- the significant difference test was performed to check whether there was a significant difference between the + Psi group and the ⁇ Psi group at each time. First, equivariance is tested by F test. If the result is equal variance, Student's t test is used. If the result is not equal variance, t test (Welch method) when the variance is different. Tested. The significance level of the test was less than 5% on both sides.
- Example 1 ⁇ Metabolism test by long-term administration of D-psicose in rats ⁇ ⁇ experimental method ⁇ Using 3-week-old male Wistar rats (purchased from Nippon SLC Co., Ltd.), the effect of long-term administration of D-psicose on energy metabolism was examined. After pre-breeding for 1 week with a commercially available powdered feed (trade name MF: Oriental Yeast Co., Ltd.), the body weight was measured and divided into 2 groups (8 per group) so that the body weight was uniform. One is a sucrose intake group, and the other is a sucrose + D-psicose intake group.
- Rat exhalation and room air were collected in a Douglas bag (Fukuda Sangyo Co., Ltd.) every hour, and the concentrations of oxygen and carbon dioxide contained in gas analyzers G-102 and LX-710 (Iijima Electronics Co., Ltd.) For 24 hours. From the oxygen concentration and carbon dioxide concentration in exhaled breath, the oxygen concentration and carbon dioxide concentration in the indoor air, the amount of oxygen consumed by the rat and the amount of carbon dioxide produced are calculated, and the energy consumption per hour is calculated as Weststate. Calculated by the formula. The value was divided by the weight of the rat at the time of measurement, and expressed as an average value and standard deviation. The significance test was performed using Student's t test. The significance level of the test was less than 5% on both sides.
- Fig. 2 shows rat energy consumption data for each time period, with the energy consumption of each rat from the 5th to 7th weeks divided by the rat weight at the time of measurement, and the influence of the size of the rat was excluded. .
- the energy consumption was significantly higher in the sucrose + D-psicose intake group than in the sucrose intake group at 11:00 in the light period and at 5 and 6 in the dark period.
- Example 2 ⁇ Metabolism test by single intake of D-psicose in human ⁇ ⁇ experimental method ⁇ The effects of single D-psicose intake on human energy consumption, carbohydrate combustion, and lipid combustion were investigated. Each energy metabolism value was calculated by an indirect calorimetry method that was calculated by measuring the respiration (oxygen consumption and carbon dioxide excretion) of the subject. This study was conducted by two groups of single blind crossover methods on 6 healthy individuals with no smoking habits (average age 34.8 years, 3 men, 3 women, average BMI 21.4 kg / m 2 ) did. In addition, after fully explaining the experimental contents to the subjects based on the guidelines in the Declaration of Helsinki, the consent of the experiment was obtained from all the subjects.
- FIG. 3 shows the effects of human D-psicose on each energy metabolism value by dividing the energy consumption, carbohydrate burning amount and lipid burning amount from 20 minutes to 4 hours after breakfast intake by the subject's body weight.
- a general diet containing lipids when D-psicose was ingested immediately before, the energy consumption and the amount of lipid burning increased significantly compared to the control diet.
- the D-psicose intake was 2.4 g, there was no difference depending on whether or not D-psicose was taken.
- Preventive and / or ameliorating agent for lowering basal energy consumption preventing and / or improving agent for lowering basal body temperature, preventing and / or improving obesity and / or visceral fat accumulation, preventing hyperglycemia associated with increased visceral fat D-psicose for providing at least one selected from the group consisting of an agent for improving and / or improving lipid metabolism associated with increased visceral fat, and / or an agent for preventing and / or improving muscle weakness Is expected to be used.
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Abstract
Description
更に、熱産生の適応的な低下は、例えば体重を減少させる食事療法の範囲内で、またはその後に生じやすい。というのも体は栄養摂取が少なすぎると反射的に熱産生活動を制限する、つまりいわゆる貯蓄型に切り替わる。この場合、通常十分な栄養供給の再摂取の場合でさえ、熱産生はその後も望ましくないほど低下したままとなり、かつ食事療法中に減少した脂肪貯蔵が再び補充されてしまう。エネルギー消費の減少により、体は効率よく体重を減少させる薬または食事療法の効果を低下させる。この結果は、インスリンが充分に機能しないII型糖尿病、高脂血症、動脈硬化症および高血圧症などの多くの慢性疾患のリスクを増加させ、哺乳動物の生活の質を低下させ、動物の寿命を短縮化する。
特許文献2には、クロロゲン酸類またはその塩を有効成分とするエネルギー消費促進剤が開示され、特許文献3には、米糠抽出物を有効成分とするエネルギー消費促進剤が開示され、安全性が高く、エネルギー消費を促進する方法が提案されている。
特許文献4には、ガルシニアカンボジア抽出物、ギムネマシルベスタ葉抽出物、および緑茶葉抽出物を含む栄養組成物が開示され、該栄養組成物の摂取により、個体において迅速な体重減少を促進し、カロリーを燃焼させ、熱発生を増大させ、エネルギー代謝を補助し、且つ/ または食欲を抑制する方法が提案
される。
このように、血糖降下、ケモカインMCP-1の分泌抑制、マイクログリアの遊走抑制などD-プシコースの様々な機能性についてはある程度明らかにされている。しかし、本発明による熱産生刺激のために使用されるD-プシコースおよびその誘導体は、意外なほど異なった作用プロフィールにより発生し、更に、熱産生促進作用を記したものは見当たらないばかりか、どれだけの摂取量で効果があるのかに関しても、明らかにされていなかった。
本発明は、エネルギー代謝を有効に向上させる少なくともD-プシコースを含む希少糖という機能性食品を用いる解決法を提供することを目的とする。
また、基礎代謝低下、低体温、肥満抑制、内臓脂肪蓄積抑制、高血糖、高脂血、および筋肉量低下の是正が求められる疾患を効果的に治療および予防できる薬剤、日々摂取することでエネルギー消費機能低下の治療および/または予防できる健康飲食品または動物用飼料の開発が切望されている。
本発明の目的は、前記課題を解決すべく、エネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防用飲食品、飼料、医薬品、医薬部外品、口腔用組成物、化粧品、またはエネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防作用を有する飲食品用添加剤を提供することにある。
すなわち、本発明は、以下のエネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防剤からなる。
第1の発明は、D-プシコースを有効成分とするエネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防剤である。
第2の発明は、第1の発明において、エネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防剤が、飲食品、飼料、医薬品、医薬部外品、口腔用組成物、化粧品、または飲食品用添加剤に添加して、D-プシコースを成人基準で2.5g以上となるように、飲食品、飼料、医薬品、医薬部外品、口腔用組成物、化粧品、または飲食品用添加剤の形態で摂取させるためのものであることを特徴とする。
第3の発明は、第1または2の発明において、エネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防剤が、D-プシコースを成人基準で2.5g以上となるように1日1回以上継続して摂取させるためのものであることを特徴とする。
第4の発明は、第1ないし3のいずれかの発明において、ぶどう糖、果糖および/または異性化糖をアルカリ異性化することにより含ませたD-プシコースを有効成分とすることを特徴とする。
第5の発明は、第1ないし4のいずれかの発明において、D-プシコースが、D-プシコース、および/または、その誘導体であり、D-プシコースの誘導体が、D-プシコースのケトン基がアルコール基となった糖アルコール、D-プシコースのアルコール基が酸化したウロン酸、D-プシコースのアルコール基がNH2基で置換されたアミノ糖から選ばれるD-プシコース誘導体であることを特徴とする。
第6の発明は、第1ないし5のいずれかの発明において、D-プシコースを成人基準で1日用量2.5g~25gを食事と共に少なくとも2週間摂取させるためのものであることを特徴とする。
第7の発明は、第1ないし6のいずれかの発明において、エネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防を必要とするヒトを含む哺乳動物に摂取させるためのものであることを特徴とする。
第8の発明は、第1ないし7のいずれかの発明の治療および/または予防剤を対象に投与する工程を含む、エネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防方法である。
また、本発明のエネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防剤は、飲食品、飼料、医薬品、医薬部外品、口腔用組成物、化粧品、または飲食品用添加剤に添加して組成物(飲食品、飼料、医薬品、医薬部外品、口腔用組成物、化粧品、または飲食品用添加剤)の形態で摂取させるためのものであり、該組成物は、基礎エネルギー消費量の低下予防および/または改善、基礎体温の低下予防および/または改善にも有効である。さらに、本発明の栄養組成物は、安全性が高く、腎機能が減弱した高齢者においても、過剰なタンパク負荷をかけずに、長期にわたって使用することができる。
本発明により、基礎代謝低下、低体温、肥満抑制、内臓脂肪蓄積抑制、高血糖、高脂血症、および筋肉量低下の是正が求められる疾患の予防および治療を必要とするヒトを含む哺乳動物哺乳動物に摂取させるための組成物を提供することができる。より具体的には、基礎代謝低下、低体温、肥満抑制、内臓脂肪蓄積抑制、高血糖、高脂血、および筋肉量低下の是正が求められる疾患を効果的に治療および予防できる薬剤、日々摂取することでエネルギー消費機能低下の治療および/または予防できる健康飲食品または動物用飼料を提供することができる。
また、エネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防用飲食品、飼料、医薬品、口腔用組成物、またはエネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防作用を有する飲食品用添加剤を提供することができる。
摂取されたエネルギー源のうち消費されなかった分は脂肪として体内に蓄積される。ある程度のエネルギー源としての脂肪の蓄積は必要であるが、過剰に蓄積されるとさまざまな病気を生じやすくなり好ましくない。そのため、基礎代謝などのエネルギー消費量は高いほうが好ましい。
例えば、比較的容易には、特許文献8に記すような、エピメラーゼを用いた酵素的手法により調製される。また、非特許文献1に記すような化学的に製造されたものでも良い。
上記により得られたD-プシコース液は、必要により、例えば、除蛋白、脱色、脱塩などの方法で精製され、濃縮してシラップ状のD-プシコース製品を採取することができ、さらに、カラムクロマトグラフィーで分画、精製することにより99%以上の高純度の粉末品も得ることができる。このようなD-プシコースは単糖としてそのまま利用できる。
一般に自然界に多量に存在するアルドースとしてはD- グルコース、D- ガラクトース、D- マンノース、D- リボース、D- キシロース、L- アラビノースの6種類あり、それ以外のアルドースは希少糖と定義される。またケトースとしては、自然界にはD- フラクトースが比較的多く存在しているが、それ以外のケトースは希少糖といえる。ケトースの希少糖としては、D- プシコース、D- タガトース、D- ソルボース、L- フラクトース、L- プシコース、L- タガトース、L- ソルボースなどがあげられる。また糖アルコールは単糖を還元してできるが、自然界にはD- ソルビトールが比較的多いがそれ以外のものは量的には少ないので、これらも希少糖といえる。
そのなかでも、現在、大量生産が可能な希少糖としては、D-プシコースやD-アロースがある。D-プシコースは、六単糖のケトース、D-アロースは六単糖のアルドースに分類される。D-プシコースは、自然界から抽出されたもの、化学的または生物学的な方法により合成されたもの等を含め、どのような手段によっても入手可能である。D-アロースは、D-プシコースを含有する溶液にD-キシロースイソメラーゼを作用させて、D-プシコースから酵素的手法によりD-アロースを生成させる(特許文献9)などして入手できる。
「レアシュガースウィート」は、異性化糖を原料とし、特許文献10に開示される手法により得られる希少糖を含有するシロップであり、希少糖として主にD-プシコースおよびD-アロースが含まれるように製造されたものである。該手法により得られる希少糖含有シロップに含まれる希少糖は、全糖に対する割合でD-プシコース0.5~17質量%、D-アロース0.2~10質量%であるが、未同定の希少糖も含まれる。
くはD-フラクトース含量が55~99質量%になるまでアルカリ異性化したシロップが主に使用される。希少糖の測定方法は種々存在するが、高速液体クロマトグラフィーにより分離測定する方法が一般的であり、測定条件の一例として、特許文献9に記載の測定条件が挙げられる(検出器;RI、カラム;三菱化成(株)MCI GEL CK 08EC、カラム温度;80℃、移動相;精製水、移動相流量;0.4mL/min、試料注入量;10μL)。
例えば、D-フラクトースを原料とした希少糖含有シロップは、D-プシコース5.2%、D-アロース1.8%、グルコース15.0%、D-フラクトース69.3%を含んでいる。また、異性化糖を原料とした希少糖含有シロップは、D-プシコース3.7%、D-アロース1.5%、グルコース45.9%、D-フラクトース37.7%を含み、D-グルコースを原料とすると、D-プシコース5.7%、D-アロース2.7%、グルコース47.4%、D-フラクトース32.1%を含んでいるが、原料および処理方法の違いにより含有糖組成は変化する。
誘導体とは、ある出発化合物から分子の構造を化学反応により変換した化合物の呼称である。例えば、六単糖であれば、糖アルコールやアミノ糖などが誘導体となる。D-プシコースの場合、ケトン基がアルコール基となった糖アルコール、アルコール基が酸化したウロン酸、アルコール基がNH2基で置換されたアミノ糖がD-プシコースの誘導体となる。
特に、単糖の生理作用の場合、酵素に対する特異性が主な作用メカニズムの原因となっており、糖の立体構造が特に重要である。一例として、肝臓におけるフラクトキナーゼという酵素は、フラクトースを主な基質としリン酸化する。フラクトースのC-3位の異性体であるD-タガトースやD-プシコースもこの酵素によりリン酸化されるが、そのリン酸化速度は各々の立体構造により異なることが知られている(非特許文献2)。この酵素では、特に、2、3、4、5位の炭素の関係がトランスであるか、アキシャルであるかによって、反応速度に影響が認められる。よって、誘導体であってもその立体構造がある程度保たれていれば、十分本発明の作用が認められることが推測される。
また、例えば、せんべい、あられ、おこし、餅類、まんじゅう、ういろう、あん類、羊羹、水羊羹、錦玉、ゼリー、カステラ、飴玉などの各種和菓子、パン、ビスケット、クラッカー、クッキー、パイ、プリン、バタークリーム、カスタードクリーム、シュークリーム、ワッフル、スポンジケーキ、ドーナツ、チョコレート、チューインガム、キャラメル、キャンディーなどの各種洋菓子、アイスクリーム、シャーベットなどの氷菓子、果実のシロップ漬、氷蜜などのシロップ類、フラワーペースト、ピーナッツペースト、フルーツペーストなどのペースト類、ジャム、マーマレード、シロップ漬、糖菓などの果実、野菜の加工食品類、パン類、麺類、米飯類、人造肉などの穀類加工食品類、福神漬、べったら漬、千枚漬、らっきょう漬などの漬物類、たくわん漬の素、白菜漬の素などの漬物の素類、ハム、ソーセージなどの畜産製品類、魚肉ハム、魚肉ソーセージ、カマボコ、チクワ、天ぷらなどの魚肉製品、ウニ、イカの塩辛、酢コンブ、さきするめ、ふぐのみりん干しなどの各種珍味類、のり、山菜、するめ、小魚、貝などで製造される佃煮類、煮豆、ポテトサラダ、コンブ巻などの惣菜食品、乳製品、魚肉、畜肉、果実、野菜の瓶詰め、缶詰類、合成酒、果実酒、洋酒、リキュールなどの酒類、コーヒー、ココア、ジュース、炭酸飲料、乳酸飲料、乳酸菌飲料などの清涼飲料水、プリンミックス、ホットケーキミックスなどのプレミックス粉類、即席ジュース、即席コーヒー、即席汁粉、即席スープなど即席飲食品などの各種飲食物への添加剤として利用できる。
特に機能性を持たせた飲料としては、コーラなどの炭酸飲料、スポーツ飲料、果汁飲料、乳性飲料、茶系飲料などを挙げることができるが、特に大量飲用により肥満の問題の生ずる炭酸飲料が格好のターゲットと言うことができる。
本発明の組成物の、前記生体作用改善を目的とした食品素材あるいは食品添加物としての使用形態としては、錠剤、カプセル剤、飲料などに溶解させる粉末あるいは顆粒などの固形剤、ゼリーなどの半固形体、飲料水などの液体、希釈して用いる高濃度溶液などがある。
さらに、本発明の組成物を適宜食品に添加して生体機能改善などを目的とした保健食または病人食とすることができる。任意的成分として、通常食品に添加されるビタミン類、炭水化物、色素、香料など適宜配合することができる。食品は液状または固形の任意の形態で食することができる。ゼラチンなどで外包してカプセル化した軟カプセル剤として食することができる。カプセルは、例えば、原料ゼラチンに水を加えて溶解し、これに可塑剤(グリセリン、D-ソルビトールなど)を加えることにより調製したゼラチン皮膜でつくられる。
これらの治療剤および予防剤は、ヒト以外の動物、例えば、牛、馬、豚、羊などの家畜用哺乳類、鶏、ウズラ、ダチョウなどの家禽類、は虫類、鳥類或いは小型哺乳類などのペット類、養殖魚類などにも用いることができる。
水、ゼラチン、乳糖、デンプン、ステアリン酸マグネシウム、タルク、動・植物油、ベンジルアルコール、ガム、ポリアルキレングリコール、石油樹脂、ヤシ油、ラノリン、または医薬に用いられる他のキャリアー(担体)は全て、本発明の組成物を含む薬剤の担体として用いることができる。また、安定剤、湿潤剤、乳化剤や、浸透圧を変えたり、配合剤の適切なpHを維持するための塩類を補助薬剤として適宜用いることができる。
本発明の組成物は、上記のような基礎エネルギー消費量の低下予防および/または改善に有用である。
特に、高齢者においては、体温調節能も減弱しており、低下した体温を上昇させることは容易ではない。本発明の組成物は、上記のような基礎体温の低下予防および/または改善に有用である。
肥満の人はしばしば血圧の上昇および/または心臓障害も合わせ持っていることが多いので、薬剤としては熱産生エネルギー消費を向上させ、かつ血圧を上昇させない薬剤が特に有利である。
本発明の組成物は、上記のような肥満、内臓脂肪蓄積の予防および/または改善に有用である。
本発明に係る栄養組成物は、上記のような内臓脂肪増加伴う高血糖の予防および/または改善に有用である。
本発明の組成物は、内臓脂肪増加伴う血中LDLコレステロールの増加等の脂質代謝異常の発症を有効に抑制することができ、内臓脂肪増加に伴う脂質代謝異常の予防および/または改善に有用である。
本発明の組成物は、筋肉量が低下した人(例えば、高齢者、寝たきり者等)の筋肉量の増加および/または筋肉量の低下抑制に好ましく使用される。
《ラットでのD-プシコース単回経口投与による代謝試験》
〔実験方法〕
7週齢の雄性Sprague-Dawleyラット(日本クレア(株)より購入)を用いて、D-プシコースの単回経口投与によるエネルギー代謝への影響を調べた。市販固形飼料(商品名CE-2:日本クレア(株))で1週間予備飼育後、体重を測定し、体重が均等になるように3群(各群8匹ずつ)に分けた。表1に示すように、一つはグルコース+フルクトース投与群(-Psi群)、一つはグルコース+フルクトース+プシコース投与群(+Psi群)、もう一つは水のみを摂取させる投与群(水投与群)である。
熱量測定試験前日16時よりラットを小動物用呼吸代謝計測システムMK-5000(室町機械(株)製)のケージに1匹ずつ入れ、間接熱量測定および馴化を開始し、飼料は与えず暗期状態とした。
翌朝10時より点灯を行い明期状態とした。各ラットの体重を測定し、3時間の馴化を行なった後、+Psi群にはプシコースを含んだ投与物を、-Psi群にはプシコースを含まない投与物を、5ml/(300g体重)となるように各ラットにゾンデにて強制経口投与した。表1に投与物を記すが、全エネルギー量を合わせるために溶液濃度を変えている。また水投与群には水のみを摂取させた。その後は純水のみ摂取可能とし、23℃、明期状態にて、翌日10時まで継続的に熱量を測定した。
安静時エネルギー代謝(Resting energy expenditure;以下REE:kcal/min)は、Weirの式を用い、体重(以下BW;kg)で除して算出した。投与12分前~60分前の測定値の平均を0時間の値とし、それからの変化量を算出後、各ラットについて値を12分ごとに平均した。さらに同じ群のラットの値を平均し、各時間帯において+Psi群(またはPsi群)のデータから水投与群のデータの平均値を差し引いて、ΔREE/BWとして表した。
有意差検定は、それぞれの時間での-Psi群に対する+Psi群の有意差の有無を検定した。まず、F検定にて等分散を検定し、結果が等分散である場合にはStudent’s t検定にて、結果が等分散でない場合には分散が異なる時のt検定(Welch法)にて検定した。検定の有意水準は両側5%未満とした。
結果を図1に示す。12分ごとの平均値で示したΔREE/BWでは、両群間で有意な差は認められなかった。炭水化物のみの食事では、同時にD-プシコースを摂取しても、炭水化物摂取直後のラットへのエネルギー消費への影響はみられなかった。ヒトに対する試験でもラット試験と同様に、炭水化物のみの食事では、D-プシコースを単回摂取してもエネルギー消費への影響はみられなかった。
《ラットでのD-プシコース長期投与による代謝試験》
〔実験方法〕
3週齢の雄性Wistar系 ラット(日本エスエルシー(株)より購入)を用いてD-プシコースの長期投与によるエネルギー代謝への影響を調べた。市販粉末飼料(商品名MF:オリエンタル酵母(株))で1週間予備飼育後、体重を測定し、体重が均等になるように2群(各群8匹ずつ)に分けた。一方はショ糖摂取群、もう一方はショ糖+D-プシコース摂取群である。
ラットを2群に分けた後、表2に示す実験飼料と水を自由摂取とし、飼育条件(温度22±1℃、湿度58±2%、明期8:00~20:00、暗期20:00~翌8:00)で飼育した。実験飼料摂取後5~7週目にエネルギー代謝の測定を以下のように実施した。まず、各群のラットを1匹ずつ密閉したポータブルデシケーター(アズワン(株)製)に入れ、通気口から1.27L/minの室内空気を電磁式エアーポンプ(アズワン{株)製)で継続的に送り込んだ。ラットの呼気および室内空気を1時間ごとにDouglasバッグ((株)フクダ産業製)に採取し、含まれる酸素と二酸化炭素の濃度をガス量分析器G-102およびLX-710(飯島電子工業(株)製)を用いて24時間測定した。呼気中の酸素濃度と二酸化炭素濃度、室内空気中の酸素濃度と二酸化炭素濃度から、ラットが消費した酸素量と生成された二酸化炭素量を算出し、1時間ごとのエネルギー消費量をWeststrateの計算式により算出した。
値は測定時のラット重量で除し、平均値および標準偏差で表わし、有意差検定はStudent’s t検定を用いて行った。検定の有意水準は両側5%未満とした。
5週目~7週目の各ラットのエネルギー消費量を測定時のラット重量で除し、ラットの大きさの影響を排除した、各時間帯でのラットのエネルギー消費量データを図2に示す。明期の11時、暗期の5時および6時においてショ糖摂取群に比べてショ糖+D-プシコース摂取群で有意にエネルギー消費量は高値を示した。
《ヒトでのD-プシコース単回摂取による代謝試験》
〔実験方法〕
ヒトにおけるD-プシコース単回摂取によるエネルギー消費、炭水化物燃焼、脂質燃焼への影響を調べた。各エネルギー代謝値は、被験者の呼吸(酸素消費量および二酸化炭素排泄量)を測定することで算出する間接熱量測定法により算出した。本試験は、喫煙習慣のない健常人6名(平均年齢34.8才、男性3名、女性3名、平均BMI21.4kg/m2)に対し、2群のシングルブラインド・クロスオーバー法により実施した。なお、被験者にはヘルシンキ宣言によるガイドラインに基づいて実験内容を十分に説明したあと、被験者全員から実験の同意書を得た。
試験開始12時間前より被験者を絶食させた後、D-プシコース5gあるいは、対照食として高甘味度甘味料アスパルテーム10mgの添加によって甘味度を同一にした試験液150mlのいずれかを摂取させた。なお、各試験液の濃度はD-プシコース群では3.3%、アスパルテーム群では0.005%であった。試験液の摂取後、朝食(ハンバーグおよびご飯)(総カロリー:571kcal、たんぱく質13.4%・脂質25.3%・炭水化物61.3%)を摂取させた。
朝食摂取後、20分間ベッドの上で安静仰臥位にて環境馴化した後、呼吸フードと連結したエアロモニタAE-310S(ミナト医科学(株)製)にて呼吸測定を行った。測定は朝食摂取後4時間まで行い、1分毎に被験者の酸素消費量および二酸化炭素排泄量を測定し、各測定値からElwynのエネルギー計算式を用いて、エネルギー消費量、炭水化物燃焼量および脂質燃焼量を算出した。呼吸測定中は、ベッドの上で安静仰臥位にて眠らずに過ごし、絶飲食とした。
得られた結果は、被験者の体重で除し、平均値及び標準偏差で表わし、有意差検定は対応のあるStudent’s t検定を用いて行った。検定の有意水準は両側5%未満とした。
朝食摂取後20分から4時間までのエネルギー消費量、炭水化物燃焼量および脂質燃焼量を被験者の体重で除し、ヒトでのD-プシコースが及ぼす各エネルギー代謝値への影響を図3に示す。脂質を含んだ一般的な食事の場合、D-プシコースを直前に摂取した場合では、エネルギー消費量および脂質燃焼量が対照食と比較して有意に上昇した。なお、D-プシコースの摂取量が2.4gではD-プシコース摂取の有無による差はみられなかった。
[実施例3]
[実験方法]
喫煙習慣のない健常人5名(平均年齢35.0才、男性3名、女性2名)を被験者とした。なお、被験者にはヘルシンキ宣言によるガイドラインに基づいて実験内容を十分に説明したあと、被験者全員から実験の同意書を得た。
まず被験者には、サンプルA(D-プシコース1.0g)を1日1回2週間継続して服用してもらった。その後、問診を実施し身体の変化を聞いた。次に1週間期間をあけてから同一の被験者に、サンプルB(D-プシコース2.5g)をサンプルAと同様に2週間継続して服用してもらい、その後問診を実施した。さらに1週間期間をあけてから同一の被験者に、サンプルC(D-プシコース5.0g)を同様に服用してもらい、問診を実施した。
問診の結果を表に示す。D-プシコースを2.5g以上継続的に摂取することにより被験者全員に変化が現れ、「体が軽くなった」、「体温が高まった」、「身体が動かしやすくなった」との印象が聞かれた。さらに、「疲れが残りにくくなった」、「気分が明るくなった」との印象も聞かれた。なお、サンプルCでの試験後、1週間期間をあけてサンプルAの2週間継続摂取試験を実施したが1回目と同様の結果であった。
D-プシコースを2.5g以上2週間継続して摂取することで、体が温まるなどひとの体感性において改善が認められた。
Claims (8)
- D-プシコースを有効成分とするエネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防剤。
- 飲食品、飼料、医薬品、医薬部外品、口腔用組成物、化粧品、または飲食品用添加剤に添加して、単位製剤当たり、D-プシコースを成人基準で1回当たり2.5g以上となるように、飲食品、飼料、医薬品、医薬部外品、口腔用組成物、化粧品、または飲食品用添加剤の形態で摂取させるためのものである、請求項1に記載の治療および/または予防剤。
- D-プシコースを成人基準で2.5g以上となるように1日1回以上継続して摂取させるためのものである、請求項1または2に記載の治療および/または予防剤。
- ぶどう糖、果糖および/または異性化糖をアルカリ異性化することにより含ませたD-プシコースを有効成分とする、請求項1ないし3のいずれかに記載の治療および/または予防剤。
- D-プシコースが、D-プシコース、および/または、その誘導体であり、D-プシコースの誘導体が、D-プシコースのケトン基がアルコール基となった糖アルコール、D-プシコースのアルコール基が酸化したウロン酸、D-プシコースのアルコール基がNH2基で置換されたアミノ糖から選ばれるD-プシコース誘導体である、請求項1ないし4のいずれかに記載の治療および/または予防剤。
- D-プシコースを成人基準で1日用量2.5g~25gを食事と共に少なくとも2週間摂取させるためのものである、請求項1ないし5のいずれかに記載の治療および/または予防剤。
- エネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防を必要とするヒトを含む哺乳動物に摂取させるためのものである、請求項1ないし6のいずれかに記載の治療および/または予防剤。
- 請求項1ないし7のいずれかに記載の治療および/または予防剤を対象に投与する工程を含む、エネルギー消費の促進および/またはエネルギー消費機能低下の治療および/または予防方法。
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Also Published As
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JPWO2014175119A1 (ja) | 2017-02-23 |
EP2992887A1 (en) | 2016-03-09 |
CN105188709A (zh) | 2015-12-23 |
KR20150145262A (ko) | 2015-12-29 |
MY196089A (en) | 2023-03-14 |
EP2992887B1 (en) | 2021-03-03 |
KR102303570B1 (ko) | 2021-09-16 |
JP6581902B2 (ja) | 2019-09-25 |
EP2992887A4 (en) | 2016-11-30 |
US20160151305A1 (en) | 2016-06-02 |
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