JP2008156341A - Agent for reducing waist size - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medicine or food effective for reduction of a waist size, leading to prevention and/or cure of a metabolic syndrome. <P>SOLUTION: A medicine for cure and/or prevention of a metabolic syndrome (1) containing hesperidin and/or its derivative (α-glucosyl hesperidin), an agent for reducing visceral fat (2) containing hesperidin and/or its derivative and an agent for reducing a waist size (3) containing hesperidin and/or its derivative are provided. The hesperidin and/or its derivative (α-glucosyl hesperidin) have been found to have excellent functions for reducing a waist size, a waist/hip size ratio, a weight and the like when administered to adult men and women selected based on a diagnostic criterion for a metabolic syndrome. The hesperidin and/or its derivative, therefore, is extremely useful for cure and/or prevention of a metabolic syndrome. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a therapeutic and / or preventive agent for metabolic syndrome, a visceral fat lowering agent, and a waist circumference reducing agent containing hesperidin and / or a derivative thereof.

  The main diseases called lifestyle-related diseases are “obesity”, “hypertension”, “diabetes”, etc., but these diseases are caused by the accumulation of fat in the internal organs rather than being caused by individual causes. Has been found to be the cause. A state in which various diseases are easily caused by visceral fat accumulation has been attracting attention as “metabolic syndrome” and has recently been considered as a treatment target (for example, Non-Patent Document 1). reference).

  In April 2005, the joint society of eight societies announced the diagnostic criteria for metabolic syndrome in Japan, and the waist circumference (85 cm or more for men, 90 cm or more for women) became an essential item. In addition to this, (1) neutral fat 150 mg / dL or higher and / or HDL 40 mg / dL or lower, (2) systolic blood pressure 130 mmHg or higher and / or diastolic blood pressure 85 mmHg or higher, (3) fasting blood glucose 110 mg / dL or higher When two or more items are satisfied, metabolic syndrome is diagnosed (see Non-Patent Document 2).

  The degree of obesity (eg, BMI [weight (kg) / height (m) squared)) does not necessarily correlate with visceral fat mass. For example, it is a well-known fact that an increase in visceral fat is recognized even in a normal weight person and that a wrestler has less visceral fat. Further, as described above, since the waist circumference is an essential diagnostic item for metabolic syndrome, reducing visceral fat should be the first priority for this treatment. There are currently no specific drug therapies for reducing visceral fat, and as expected to be effective, α-glucosidase inhibitors that are sugar absorption inhibitors and thiazolidine drugs that are insulin resistance improvers Is only known (see, for example, Non-Patent Document 3).

  On the other hand, hesperidin is a kind of polyphenol contained in orange peel and is also called vitamin P. The action is a very useful substance having a capillary strengthening action, a blood lipid improving action, a blood flow improving action, an antiallergic action, a carcinogenesis suppressing action and the like (for example, see Non-Patent Document 4). Furthermore, it has been clarified that hesperidin has a lipase inhibitory activity and a neutral fat lowering action in blood, suggesting that it is useful for the prevention and treatment of obesity (Patent Document 1). In addition, hesperidin (also referred to as glycosyl transfer vitamin P or α-glucosyl hesperidin) in which hesperidin has water solubility and is substantially tasteless and odorless to facilitate formulation, is obtained by binding sugar to hesperidin. Have been developed (see, for example, Patent Document 2).

However, as mentioned above, even if a triglyceride-lowering action or anti-obesity action is suggested, it is clear that it does not directly suggest a reduction in visceral fat mass. There are no reports that metastasized hesperidin has a visceral fat lowering action or waist circumference reducing action.
Kaken Pharmaceutical Co., Ltd. All rights reserved [searched on November 7, 2006], Internet <http://metabolic.jp/> Japan Medical News No. 4284 (June 3, 2006) p. 73 Prog. Med. Vol. 24 2004 p. 2161 Ezaki Glico Co., Ltd. Homepage, “Materials Knowledge”, [Search August 10, 2006], Internet <http://www.ezaki-glico.net/sozai/index.html> JP-A-9-143070 Japanese Patent No. 3060227

  An object of the present invention is to provide an effective pharmaceutical or food product that reduces the waist circumference, and thus to provide an effective pharmaceutical product or food for the prevention and / or treatment of metabolic syndrome.

  In order to find a pharmaceutical or food useful for prevention and / or treatment of metabolic syndrome, the present inventors have a waist circumference (male 85 cm or more, female 90 cm or more) and neutral fat 150 mg, which are diagnostic criteria for metabolic syndrome. Clinical trials were conducted on adult males and females corresponding to the above by randomized assignment and double blind.

  As a result, it has been found that hesperidin and / or a derivative thereof (glycosylated hesperidin) have an excellent waist circumference reducing action, a waist / hip ratio reducing action, a weight reducing action and the like. This result does not revert, but also means that it is extremely useful for the reduction of visceral fat and thus the treatment and / or prevention of metabolic syndrome.

  Further, the effect is not dependent on the dose of hesperidin and / or its derivative, and it has been newly found that the effect is reduced when a certain dose is exceeded, and the present invention has been completed.

That is, the present invention
(1) A therapeutic and / or prophylactic agent for metabolic syndrome containing hesperidin and / or a derivative thereof,
(2) a visceral fat reducing agent containing hesperidin and / or a derivative thereof,
(3) A waist circumference reducing agent containing hesperidin and / or a derivative thereof,
(4) The therapeutic and / or preventive agent for metabolic syndrome according to (1) above, wherein the hesperidin and / or derivative thereof is administered at a dose of 10 mg to 1000 mg per day, the visceral fat lowering agent according to (2) above or (3 ) Waist circumference reducing agent,
(5) The therapeutic and / or preventive agent for metabolic syndrome according to (1) above, wherein the hesperidin and / or derivative thereof is administered at 20 mg to 750 mg per day, the visceral fat reducing agent according to (2) above or (3 above) ) Waist circumference reducing agent,
(6) The therapeutic and / or preventive agent for metabolic syndrome according to (1) above, wherein the hesperidin and / or derivative thereof is administered at 50 mg to 500 mg per day, the visceral fat reducing agent according to (2) above or (3 ) Waist circumference reducing agent,
(7) The therapeutic and / or preventive agent for metabolic syndrome according to (1) above, wherein the hesperidin and / or derivative thereof is glycosylated hesperidin, the visceral fat lowering agent according to (2) above or the waist circumference according to (3) above Diameter reducing agent,
(8) A therapeutic and / or prophylactic agent for metabolic syndrome according to (1) above, which is a pharmaceutical, a visceral fat reducing agent according to (2) above, or a waist circumference reducing agent according to (3) above,
(9) The therapeutic and / or preventive agent for metabolic syndrome according to (1) above, which is a food, the visceral fat reducing agent according to (2) above, or the waist circumference reducing agent according to (3) above,
It is about.

  As will be apparent from the examples described later, hesperidin and / or a derivative thereof according to the present invention is excellent in reducing the waist circumference, reducing the waist / hip ratio, reducing the body weight, etc. showed that. Therefore, it is possible to provide a pharmaceutical or food that reduces visceral fat and waist circumference, and is therefore useful as a therapeutic and / or prophylactic agent for metabolic syndrome.

  Hesperidin according to the present invention is a kind of polyphenol contained in orange peel and is also called vitamin P. Hesperidin is listed in the Japanese Pharmacopoeia Standards for Drugs 2002, is also listed in the Food Additives List, and is readily available.

  In addition, glycosylated hesperidin, which is a derivative of hesperidin, has been improved in water solubility by binding sugar to hesperidin, also called glucosyl hesperidin or glycosylated vitamin P, and is also commercially available as a food additive. Easy to obtain.

  The daily dose or intake of hesperidin and / or its derivatives varies depending on the indication and age, but is usually 10 mg to 1000 mg, preferably 20 mg to 750 mg, more preferably 50 mg to 500 mg. It may be taken or taken in 1 to 3 times a day.

  The dosage form of the therapeutic and / or prophylactic agent for metabolic syndrome, visceral fat lowering agent, waist circumference reducing agent (hereinafter sometimes referred to generically as the therapeutic and / or prophylactic agent for metabolic syndrome) of the present invention. In the case of a solid or semi-solid preparation, the content of hesperidin or a derivative thereof contained in a daily dose is usually 10 mg to 1000 mg, preferably 20 mg to 750 mg, more preferably 50 mg to 500 mg. is there.

  The therapeutic and / or prophylactic agent for metabolic syndrome of the present invention includes, in addition to the above-described hesperidin and / or derivatives thereof, blood lipid lowering agents such as fibrate preparations and HMG-CoA reductase inhibitors, and various antihypertensive agents. Various antidiabetic drugs or insulin resistance therapeutic drugs, anti-obesity drugs, vitamins, herbal medicines, various health food materials, and the like can be contained within a range not impairing the effects of the present invention.

  Specific examples of the therapeutic and / or preventive agent for metabolic syndrome of the present invention include, for example, tablets, chewing tablets, fine granules (including granules and powders), capsules, liquids, etc. Medicines, cookies, gum, chocolate, candy, drop, marmalade, mayonnaise, dressing, bread, pudding, tableting confectionery, powdered juice, sprinkles or toppings, beverages, etc. In addition, food additives, base materials, and the like can be used as appropriate, and can be produced according to the usual methods described in the Japanese Pharmacopoeia and the like.

  For example, in the case of tablets, lactose, crystalline cellulose or the like as an excipient, magnesium metasilicate aluminate or magnesium oxide as a stabilizer, hydroxypropyl cellulose or the like as a coating agent, magnesium stearate or the like as a lubricant In the case of fine granules and capsules, lactose or purified sucrose is used as an excipient, magnesium aluminate or magnesium oxide as a stabilizer, corn starch or the like as an adsorbent, hydroxy Propyl cellulose or the like can be used as a binder. In addition, in each form, if necessary, a disintegrant such as crospovidone, a surfactant such as polysorbate, an adsorbent such as calcium silicate, a colorant such as iron sesquioxide or caramel, a stabilizer such as sodium benzoate, A pH regulator, a fragrance, and sugar, syrup, cocoa butter, butter, margarine, edible fats and oils, salt, condensed milk, flour, other food materials and food additives, and the like can be blended.

  The hesperidin and / or derivative thereof according to the present invention is taken or ingested for the purpose of reducing visceral fat or reducing the waist circumference, and for the purpose of treating and / or preventing metabolic syndrome. Therefore, hesperidin and / or a derivative thereof according to the present invention can be used as a pharmaceutical product or a food according to the above purpose.

Examples are described below to explain the present invention in more detail, but the present invention is not limited to these (Formulation Example 1) Tablets (1) Ingredients 2 tablets (mg) (1a) ( 1b)
―――――――――――――――――――――――――――
Hesperidin 500 −
Glycosyl hesperidin-500
Erythritol 89 89
Fine silicon dioxide 6 6
Magnesium stearate 5 5
―――――――――――――――――――――――――――
(2) Manufacturing method Taking the said component and quantity, the tablet was manufactured according to the 15th revision Japanese Pharmacopoeia preparation general rule "Tablet".
(Formulation example 2) Powder (fine granules)
(1) In ingredient 1 package (mg) (2a) (2b)
―――――――――――――――――――――――――――
Hesperidin 500 −
Glycosyl hesperidin-500
Lactose 130 130
Erythritol 300 300
Light anhydrous silicic acid 50 50
Hydroxypropyl cellulose 10 10
Magnesium stearate 10 10
―――――――――――――――――――――――――――
(2) Manufacturing method Taking the said component and quantity, the fine granule was manufactured according to the 15th revision Japanese Pharmacopoeia preparation general rule "granule".
(Formulation example 3) Hard capsule (1) In component 4 capsule (mg) (3a) (3b)
―――――――――――――――――――――――――――
Hesperidin 500 −
Glycosyl hesperidin-500
Lactose 100 100
Erythritol 150 150
Light anhydrous silicic acid 40 40
Magnesium stearate 10 10
―――――――――――――――――――――――――――
(2) Manufacturing Method After taking the above-mentioned components and quantities, and producing a fine granule according to the section of the 15th revised Japanese Pharmacopoeia General Rules for “Granules”, it was filled into a capsule to produce a hard capsule.
(Example 4) Solution (1) In 60 mL of component (mg) (4a)
――――――――――――――――――――――
Transglycosyl hesperidin 500
Sodium benzoate 100
Polyvinyl alcohol 50
Sucrose 900
Purified water balance ――――――――――――――――――――――
(2) Manufacturing method After taking the said component and quantity and manufacturing a syrup preparation according to the term of a Japanese pharmaceutical formulation general rule "syrup preparation", it filled with the brown glass bottle and manufactured the syrup preparation.
(Example 5) In white chocolate (1) component 1 block 100g (g) (5a) (5b)
―――――――――――――――――――――――――――
Hesperidin 0.5 −
Glycosyl hesperidin-0.5
Bitter chocolate 18 18
Cocoa butter 22 22
Whole milk powder 20 20
Lecithin 0.3 0.3
Vanillin Trace Trace sugar Remaining remainder ------------
(2) Manufacturing method The said component and quantity were taken and it manufactured according to the normal chocolate manufacturing method.
(Example 6) Candy (1) Ingredient 1 block 100g (g) (6a) (6b)
―――――――――――――――――――――――――――
Hesperidin 0.5 −
Glycosyl hesperidin-0.5
Mizuame 55 55
Citric acid Appropriate amount Appropriate amount Fragrance Trace amount of sugar Remaining part Remaining part
(2) Manufacturing method The said component and quantity were taken and it manufactured according to the normal candy manufacturing method.
(Example 7) Bread (1) Ingredient 1 block 100g (g) (6a) (6b)
―――――――――――――――――――――――――――
Hesperidin 0.5 −
Glycosyl hesperidin-0.5
Flour 85 85
Salt Suitable amount Suitable amount Shortening Suitable amount Suitable amount Yeast 3 3
Water remainder remainder ――――――――――――――――――――――――――――
(2) Manufacturing method The said component and quantity were taken and it manufactured according to the normal bread manufacturing method.
(Test example)
(1) Test substance The glycosylated hesperidin used was a food additive standard (manufactured by Hayashibara Biochemical Laboratories). The test drug was produced by tableting the product shown in (1b) of Example 1. In addition, a placebo was prepared by tableting containing corn starch and crystalline cellulose instead of sugar-transferred hesperidin.
(2) Subjects: Placebo group, glycosylated hesperidin for 40 adult males and females with a waist circumference (male 85 cm or greater, female 90 cm or greater) and fasting neutral fat 150 mg or greater, which is a diagnostic criterion for metabolic syndrome Four groups (9 to 12 people per group) of 250 mg, 500 mg and 1000 mg groups were assigned daily by the randomized method.
(3) Test The test was conducted by double blind. The test substance is taken once daily with water or hot water. The intake period was 4 weeks, and the test was performed 3 times before intake, 2 weeks after intake, and 2 weeks after completion of intake. Breakfast and dinner 3 days before and 2 days before each examination day, breakfast, lunch and dinner the previous day were standardized for all subjects. Furthermore, during these three days, high-fat meals, night meals, and drinking were prohibited, and dinner was completed by 19:00 on the previous day, after which only water was consumed. On the morning of the examination, body weight, waist and hip circumference were measured.
(4) Test results Each measured value was calculated by converting the average before taking the test drug or placebo as 1.

  The result of the obtained weight fluctuation rate is shown in FIG. 1, the result of the obtained waist circumference fluctuation rate is shown in FIG. 2, and the result of the obtained waist / hip ratio fluctuation rate is shown in FIG.

  From FIG. 1, it was found that a decrease in body weight was observed by administration of glycosylated hesperidin, and that the effect diminished when the dose exceeded a certain level.

  From FIG. 2, it was found that administration of glycosylated hesperidin resulted in a decrease in waist circumference and that the effect diminished when the dose exceeded a certain level.

  From FIG. 3, it was found that the waist / hip ratio was decreased by administration of glycosylated hesperidin, and that the effect decreased when the dose exceeded a certain level.

  The hesperidin and / or derivative thereof according to the present invention showed an excellent visceral fat lowering action, a waist circumference reducing action and the like for patients corresponding to metabolic syndrome. Therefore, it is suitable for the purpose of treatment and / or prevention of metabolic syndrome, and can be used as a pharmaceutical or health food.

FIG. 1 shows, on the vertical axis, the rate of change in body weight at 2 weeks after intake, 4 weeks after intake, and 2 weeks after completion of intake relative to the value before intake for each intake of glycosylated hesperidin. FIG. 2 shows, on the vertical axis, the fluctuation rate of the waist circumference after 2 weeks of intake, 4 weeks after intake, and 2 weeks after completion of intake with respect to the value before intake for each intake of glycosylated hesperidin. FIG. 3 is a graph showing the fluctuation rate of the waist / hip ratio on the vertical axis after 2 weeks of intake, 4 weeks of intake, and 2 weeks after completion of intake, with respect to the values before intake for each intake of glycosylated hesperidin. .

Claims (9)

A therapeutic and / or prophylactic agent for metabolic syndrome containing hesperidin and / or a derivative thereof. A visceral fat lowering agent containing hesperidin and / or a derivative thereof. A waist circumference reducing agent containing hesperidin and / or a derivative thereof. The therapeutic and / or prophylactic agent for metabolic syndrome according to claim 1, the visceral fat lowering agent according to claim 2, or the waist circumference according to claim 3, wherein hesperidin and / or a derivative thereof is administered at a dose of 10 mg to 1000 mg per day. Reducing agent. The therapeutic and / or preventive agent for metabolic syndrome according to claim 1, the visceral fat lowering agent according to claim 2, or the waist circumference according to claim 3, wherein hesperidin and / or a derivative thereof is administered at a dose of 20 mg to 750 mg per day. Reducing agent. The therapeutic and / or preventive agent for metabolic syndrome according to claim 1, the visceral fat lowering agent according to claim 2, or the waist circumference according to claim 3, wherein hesperidin and / or a derivative thereof is administered at a dose of 50 mg to 500 mg per day. Reducing agent. The therapeutic and / or preventive agent for metabolic syndrome according to claim 1, the visceral fat reducing agent according to claim 2, or the waist circumference reducing agent according to claim 3, wherein hesperidin and / or a derivative thereof is glycosylated hesperidin. The therapeutic and / or prophylactic agent for metabolic syndrome according to claim 1, which is a pharmaceutical, the visceral fat reducing agent according to claim 2, or the waist circumference reducing agent according to claim 3. The therapeutic and / or preventive agent for metabolic syndrome according to claim 1, which is a food, the visceral fat reducing agent according to claim 2, or the waist circumference reducing agent according to claim 3.