JP2008156320A - Antioxidative functional water - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new function of water containing highly concentrated nano-sized bubbles. <P>SOLUTION: Functional water containing fine bubbles generated by aerating at least one gas selected from a group consisting of air, hydrogen, oxygen and nitrogen and having hydrogen peroxide-removing action, is provided. Such functional water can be simply produced by aerating at least one gas selected from a group consisting of air, hydrogen, oxygen and nitrogen through a microfiltration membrane, an ultrafiltration membrane or a gas separation membrane. The functional water is useful for treating metabolic syndrome, adiponectin-related diseases or conditions, or hypertension treatment and the like. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to functional water containing air, hydrogen or nitrogen gas in a microbubble or nanobubble state. The functional water of the present invention has an antioxidant action. The functional water of the present invention also has the effect of promoting the production of adiponectin, which is considered as an anti-metabolic syndrome hormone, and lowering blood pressure. The functional water of the present invention is useful in the fields of food, cosmetics and pharmaceuticals.

  In recent years, functional water with various functions and effects has been proposed, and some research has begun. The definition of functional water has been proposed as water having a specific physical and chemical treatment, water having a specific substance added, and water having a specific substance removed (Non-patent Document 1).

  At present, functional water which is considered to have various physiological functions is mainly so-called acidic water or alkaline water which is electrochemically decomposed. While the former has been reported to have a bactericidal action (Non-patent Document 2), the latter has a report of improving gastrointestinal complaints (Non-patent Document 3) and eliminating reactive oxygen species. (Non-Patent Document 4), there is a report that there is no scavenging ability of active oxygen species (Non-Patent Document 5).

Recently, research on water containing fine bubbles such as microbubbles (MB), micronanobubbles (MNB), and nanobubbles (NB) has been progressing. Water containing bubbles below the micrometer has been found to have functions not found in conventional water, such as water purification, sterilization, and improvement of oxygen deficiency in aquatic organisms. ing. For example, there is a report that rapid blood flow promotion is realized when seawater microbubbles are supplied to scallops (Non-Patent Document 6). Moreover, when oxygen nanobubbles are put in the aquarium, there is a report that saltwater fish and freshwater fish can be simultaneously survived for a period of more than half a year (Patent Document 1). Further, as a means for generating fine bubbles, pressurized air generated by an air pump for the purpose of interposing bubbles or an air layer on the surface of the hull in order to reduce friction with water running on a ship or the like. A method of jetting water into a water from a plurality of holes or a perforated plate (for example, Patent Documents 2 and 3), and letting gas pass through the central cavity of a rotating gas-liquid two-phase fluid and releasing pressure at a stroke near the outlet A method for generating microbubbles at the rotationally cut portion of the cavity (Non-Patent Document 6) has been proposed.
JP 2005-246294 JP 61-71290 JP-A-8-230762 Water Science Study Group, Functional Water Practical Handbook, Human and History Company, pp13-14, 2006 T. Kitahora et al: Active oxygen species in gastric mucosal lesion with Helicobacter pylori.Current Topics in Mucosal Immunology, 289-293, 1993 Tashiro Hirokazu, et al .: Helicobacter pylori and gastric mucosal tissue-generated reactive oxygen, digestive organs and immunity, 71-73, 1996 S. Shirahata et al: Electrolyzed-reduced water scavenges active oxygen species and protects DNA from oxidative damage. Biochem. Biophys. Res. Commun., 234, 269-274, 1997 Yuji Naito, et al .: Examination of effectiveness of alkaline ionized water for gastric mucosal damage caused by non-steroidal anti-inflammatory drugs, 5th Functional Water Symposium, 67-68, 1998 Hirofumi Taisei, et al., Micro-Nano Bubble Generation Mechanism and Physiological Activity, Proceedings of Annual Meeting of Japan Multiphase Flow Society, 221-222, 2003 Ishida, N. et al., Langmuir, 16, 5681-5687, 2000

  The inventors have been engaged in research on prevention and treatment methods of metabolic syndrome for many years. And it discovered that the water which included highly safe gas, such as air and hydrogen, in a high density | concentration in the state of a nanosize bubble had various functions. Moreover, it was confirmed that the quality of such nanobubble water was stable for a long time, and the present invention was completed.

The present invention means:
1) Functional water containing fine bubbles generated by aeration of one or more gases selected from the group consisting of air, hydrogen, oxygen and nitrogen, and having hydrogen peroxide removal ability;
2) A function including fine bubbles generated by aeration of one or more gases selected from the group consisting of air, hydrogen, oxygen and nitrogen through a microfiltration membrane, an ultrafiltration membrane, or a gas separation membrane. water;
3) Functional water according to 2) above having hydrogen peroxide removing ability;
4) Functional water according to any one of 1) to 3) above for the treatment of metabolic syndrome, adiponectin, leptin, TNF-α or diseases or conditions associated with oxidative disorders, or hypertension;
5) Antioxidant functional water containing fine bubbles generated by aeration of one or more gases selected from the group consisting of air, hydrogen, oxygen and nitrogen, and having hydrogen peroxide removal ability;
6) A food composition, cosmetic composition or pharmaceutical composition comprising the functional water described in 5) above;
7) A pharmaceutical composition for the treatment of metabolic syndrome, adiponectin, leptin, TNF-α or oxidative disorder-related diseases or conditions, or hypertension, comprising the functional water described in 5) above;
8) Functional water according to any one of 1) to 3) above, wherein air is contained 50 times the theoretical dissolved value;
9) The functional water according to any one of 1) to 3) above, wherein hydrogen is contained 10 times or more of a theoretical dissolved value;
I will provide a.

  Water containing fine bubbles of a certain size or less has a negative potential, and disappears in the water by a crushing phenomenon without rising on the water surface. At that time, since it is in an ultra-high temperature / ultra-high pressure state instantaneously, it is considered that hydrogen molecules constituting water physically dissociate into atomic hydrogen. Atomic hydrogen has a reducing action and is capable of removing active oxygen. On the other hand, since hydrogen molecules are very stable, they are chemically inert at room temperature, and even if hydrogen is dissolved in water at a high concentration, the ability to scavenge active oxygen is not recognized (edited by Water Science Research Group, Functional Water Practical Handbook, pp213-225, 2006, Human and History Company). The present invention utilizes the above-described reducing action of water containing fine bubbles. Therefore, the gas used in the present invention is not particularly limited as long as it can cause such a phenomenon and is highly safe for a living body. In the present invention, for example, one or more gases selected from the group consisting of air, hydrogen, oxygen, and nitrogen can be used. Preferably, air, hydrogen or nitrogen is used, and more preferably air or hydrogen is used.

  The water that can be used in the present invention is not particularly limited as long as it is suitable for the production of foods, cosmetics or medicines. In the present invention, for example, hard water, soft water, medium hard water, ion exchange water, desalted water, tap water, sterilized water, and the like can be used.

  The functional water of the present invention contains fine bubbles generated by aeration of one or more kinds of gases as described above. A conventional technique may be used as such a method for producing functional water.

  For convenience, pressure is applied through a porous body of an organic material or an inorganic material having fine pores of micrometer or less such as a microfiltration membrane, an ultrafiltration membrane, a nanofiltration membrane or a gas separation membrane. It can be manufactured by sending gas into water. There is no restriction | limiting in particular in the raw material of the film | membrane to be used, It is suitable for manufacture of a drink, and should just be stable with respect to the pressurized gas and water to be used. A person skilled in the art can appropriately set the aeration time according to the amount of aeration, the surface area of the porous body and the amount of water, using as an index the ability to remove hydrogen peroxide that the functional water should have. For example, it is recommended to perform aeration for about 18 hours under the conditions described in the embodiment using the organic membrane module and for about 2 hours under the conditions described in the embodiment using the inorganic filter module. The temperature at the time of aeration is preferably room temperature (25 ° C.), more preferably 4 ° C. to 10 ° C. The pH at the time of aeration should just be in the range with which the porous body to be used is stable. For example, the modules described in the examples can be carried out within the range of pH 1-14.

  The obtained functional water can be evaluated by measuring its ability to remove hydrogen peroxide, weight, bubble particle size, etc., and its function can be confirmed.

  The functional water of the present invention has the ability to remove hydrogen peroxide. In the present specification, when it has “hydrogen peroxide removal ability” for functional water, except for special cases, hydrogen peroxide solution is added to the target functional water so that the hydrogen peroxide concentration becomes 10 ppm, After sealing and standing at room temperature for 3 hours, when the amount of residual hydrogen peroxide is measured, hydrogen peroxide is removed at least 30% (hydrogen peroxide concentration is 7 ppm or less). The functional water of the present invention is preferably 40% or more, more preferably 50% or more, and still more preferably 60% or more in terms of hydrogen peroxide removal ability evaluated by such measurement. . The upper limit value of the functional water peroxidation-removing ability of the present invention can be determined from the viewpoints of production, safety, storage stability, etc. it can.

  In the case of functional water produced by exposing air, as described in the examples of this specification, the weight before and after treatment was measured with a precision electronic pan balance. 0.9854g, 0.9633g after aeration, 0.0022g was lighter. Similarly, in the case of functional water produced by aeration of hydrogen, 0.9854 g before aeration and 0.917 g of aeration word were 0.0078 g lighter. Such a result is thought to have occurred because air and hydrogen were trapped in water.

  The amount of air contained in the functional water of the present invention produced by aeration of air is preferably 10 times or more the theoretical dissolved value of air in water, more preferably 50 to 3,000 times. More preferably, it is 100 to 1,000 times. The amount of hydrogen contained in the functional water of the present invention produced by aeration of hydrogen is preferably at least 3 times the theoretical dissolved value of hydrogen in water, more preferably 10 to 200 times. 20 to 50 times more preferable.

  The functional water of the present invention is an antioxidant functional water having an antioxidant action.

  The functional water of the present invention can be used as a food composition, cosmetic composition or pharmaceutical composition, or added to any of these. The food composition includes beverages and drinks.

  The functional water of the present invention can be used for various applications in which the ability to remove hydrogen peroxide or the antioxidant action has an effective effect. The functional water of the present invention may be used in particular for metabolic syndrome, adiponectin-related diseases or conditions (for example, obesity, visceral fat, lifestyle-related diseases, arteriosclerosis), leptin-related diseases or conditions (for example, obesity, anorexia, Diseases or conditions associated with reduced glycolipid metabolism), TNF-α (eg, insulin resistance, tumor) or oxidative disorders (eg, increased lipid peroxide, arteriosclerosis, myocardial infarction, diabetes, cancer, aging), or Useful for the treatment of hypertension.

  As used herein, “treatment” for a disease or condition, except for special cases, treats, prevents, delays or stops progression, or maintains a good condition for the disease or condition. The treatment includes coping treatment that suppresses symptoms and fundamental treatment.

  Adiponectin is a hormone secreted into the blood from fat cells, and is said to be effective for eliminating metabolic syndrome.

In this specification, “metabolic syndrome” is used in the normal sense, and the waist circumference is 85 cm for men and 90 cm for women (marker with visceral fat area of 100 cm ² or more) according to general diagnostic criteria. In this, "1) Serum lipid abnormality (triglyceride level 150 mg / dL or higher, or HDL cholesterol level less than 40 mg / dL), (2) High blood pressure (highest blood pressure 130 mmHg or higher, or lowest blood pressure 85 mmHg or higher" ), (3) refers to the case of having two or more of three items of hyperglycemia (fasting blood glucose level 110 mg / dL).

  The functional water of the present invention is also useful for treatment of obesity, hypertension, diabetes, hyperlipidemia, etc., as well as improvement of exercise capacity and exercise maintenance.

  The functional water of the present invention is orally taken at 100 ml or more, preferably 200 ml or more per day for adults for the purpose of treating metabolic syndrome, adiponectin, leptin, TNF-α or diseases or conditions related to oxidative disorder, or hypertension. Good. For prevention purposes, smaller amounts may be effective. There is no particular restriction on the amount of intake, but if a person with normal blood pressure drinks a large amount of functional water of the present invention produced by aeration of hydrogen, a rapid decrease in blood pressure may be seen. A single dose will preferably be less than 500 ml.

  The functional water of the present invention may contain various additives and components that are acceptable as food, cosmetics, or pharmaceuticals, in addition to fine gas bubbles and water. The functional water of the present invention includes, for example, stabilizers, buffers, flavoring agents (including sweeteners and acidulants), preservatives, fragrances, coloring agents, thickeners, vitamins, salts, fruit juices, It may contain other ingredients that are effective for the treatment of the disease or condition. When the functional water of the present invention is used as food, cosmetics or pharmaceuticals, it can be in various liquid forms such as solution, emulsion, suspension, etc., and it is solidified or semi-solidified or encapsulated. It can be in the form of a gel or capsule.

  As the container filled with the functional water of the present invention, a plastic bottle and glass are suitable.

  The contents of the present invention will be described in detail below. The devices and the like used in the present invention are only for explaining the present invention, and the present invention is not limited to this.

[Functional water production example 1]
20L deionized water pasteurized in a ceramic tank and connected to a non-oil compressor with an organic filter with a nanometer pore size (polysulfone ultrafiltration membrane module manufactured by Asahi Kasei Chemicals Corporation, product name Microza pencil type module SEP-0013, nominal molecular weight cut off 3,000). Air pressurized to ² kg / cm ² was sent into the module for 5-20 hours at room temperature. At this time, the discharge part of the module was completely sealed so as not to leak air.

[Functional water production example 2]
Inorganic filter with nanometer pore size (ceramic filter module manufactured by Noritake Co., Ltd., product name MEMBRALOX, pore size 20nm) with 20L of deionized water heat sterilized in a ceramic tank and connected to a non-oil compressor ). Air pressurized to 10 kg / cm ² was sent into the module for 10-60 minutes at room temperature. At this time, the discharge part of the module was completely sealed so as not to leak air.

[Evaluation of functional water and storage stability]
Water containing bubbles below the micrometer has a negative potential and disappears in the water by a crushing phenomenon without rising on the water surface. At that time, since it is in an ultra-high temperature / ultra-high pressure state instantaneously, it is considered that the hydrogen molecules constituting the water are physically dissociated into atomic hydrogen. Since atomic hydrogen is reducible, the most easily measurable method is reaction with hydrogen peroxide. Atomic hydrogen can eliminate hydrogen peroxide with 1: 1 equimolar reaction. The erased amount of hydrogen peroxide was measured by a simple method such as a hydrogen peroxide sensor, and used as a functional water evaluation method.

  Functional water was produced by aeration of air or hydrogen by the method described in Production Example 1. Functional water was stored in a cool dark place for 0 to 3 months.

  To each 10 ml of functional water, hydrogen peroxide solution is added so that the hydrogen peroxide concentration is 10 ppm, sealed, and allowed to stand at room temperature for 3 hours, and then the amount of residual hydrogen peroxide is measured with a hydrogen peroxide sensor. did. As a control, the amount of residual hydrogen peroxide was similarly measured for deionized water used for the production of functional water.

The hydrogen peroxide scavenging ability (%) was calculated by the following formula.
Hydrogen peroxide scavenging ability (%) = ((AH-RH) / AH) x 100
AH is the added hydrogen peroxide concentration, and RH is the residual hydrogen peroxide concentration.

  The results are shown in the table below.

  Since the control did not show hydrogen peroxide scavenging ability in any month, only the third month was listed.

  In addition, regarding the hydrogen peroxide scavenging ability, the average value and standard deviation value of 6 samples are shown in the following table.

  The hydrogen peroxide scavenging ability of each functional water gradually decreases with time after production, but it was stored for 2 months with water containing a high concentration of air and for 3 months with water containing a high concentration of hydrogen. Even in this case, it retained about 50% hydrogen peroxide scavenging ability. This is the method shown in the production example, and it is considered that when air or hydrogen is included in water at a high concentration, these gases exist in a relatively stable state. If quality assurance is possible for about 2 to 3 months, it is not impossible to distribute on a commercial scale.

[In vivo test]
Next, in order to confirm whether or not the functional water of the present invention exerts the desired action in vivo, experiments on metabolic syndrome in mice and rats were performed. As indicators, peripheral blood adiponectin, leptin, tumor necrosis factor (TNF-α), lipid peroxide and blood pressure were measured.

1. Effects of peripheral blood on adiponectin, leptin, and TNF-α:
Diabetic mice (KKAy, ♂, 7-week-old, CLEA Japan) are raised in an environment with a temperature of 25 ± 3 ° C, relative humidity of 50 ± 10%, and a light / dark cycle of 12 hours (light period 8: 00-20: 00). The diet was a high-fat diet (Claire Japan). In addition, the functional water containing air or the functional water containing hydrogen was freely ingested as drinking water. As a control, tap water used for functional water production was used.

  After raising for one month, blood was collected from the fundus vein under ether anesthesia, and serum was obtained based on a conventional method. Adiponectin, leptin, and TNF-α in serum were measured by the surface plasmon resonance method by immobilizing each antibody on a BIAcore sensor chip and based on an operation manual of BIAcore. The results are shown in the table below.

  Each factor showed the ratio in the control ratio. + Indicates an increase and-indicates a decrease.

2. Impact on oxidative damage:
Rats (Wistar / ST, ♂, 5 weeks old, Sankyo Lab Service Co., Ltd.) in an environment with a temperature of 25 ± 3 ° C, relative humidity of 50 ± 10%, and a light / dark cycle of 12 hours (light period 8: 00-20: 00) And was allowed to freely eat a normal diet (Claire Japan). The functional water containing the air was freely ingested as drinking water. As a control, tap water used for functional water production was sterilized.

  After rearing for 4 weeks, 50 μl of cumene hydroperoxide (125 μg / kg body weight) was intraperitoneally administered. Three hours later, blood was collected from the fundus vein under ether anesthesia, serum was obtained based on a conventional method, and the serum peroxide value was measured with a measurement kit (Wako Pure Chemical Industries). The results are shown in the table below.

  The serum lipid peroxide level after administration of cumene hydroperoxide was about 40% higher in the control group fed with sterile tap water, but the rate of increase was about 9% by ingesting functional water. Was suppressed.

3. Effects on blood pressure:
Spontaneously hypertensive rats (SHR / izm, ♂, 8 weeks old, Sankyo Lab Service Co., Ltd.), temperature 25 ± 3 ° C, relative humidity 50 ± 10%, light / dark cycle 12 hours (light period 8: 00-20: 00) And was fed freely with CE-2 solid feed (Claire Japan). Moreover, the functional water which included the above-mentioned air or the functional water which included hydrogen was each ingested freely as drinking water. As a control, tap water used for functional water production was sterilized. The animals were raised for 4 months under these conditions. Blood pressure was measured with a non-invasive blood pressure monitor for mice and rats (MODEL MK-2000, Muromachi Kikai Co., Ltd.).

  The results of spontaneously hypertensive rats are shown in Table 4-1 and Table 4-2.

  The blood pressure of each animal represents the average value of 6 measurements, and the numbers in () represent standard deviation values.

  The diastolic blood pressure is a value calculated by the software built in the non-invasive blood pressure monitor for mice and rats (MODEL MK-2000, Muromachi Kikai Co., Ltd.) from the measured values of the systolic phase and the average blood pressure.

  As shown in Table 4-1 and Table 4-2, the functional water of the present invention had an action of lowering blood pressure. The effect was higher when hydrogen was included than with air.

5. Effects on blood pressure of human volunteers:
A human male volunteer with 4 hypertension border areas and 1 normal blood pressure had 200 ml of functional water inclusive of air at any time of morning, noon, and evening, and blood pressure in the systolic and diastolic phases 30 minutes later Was measured. Blood pressure was measured using the home blood pressure monitor (OMRON) under the same conditions in the same facility based on the operation manual. During this period, it was confirmed that no antihypertensive drugs (antihypertensive agents) were used. The results are shown in the table below.

  5 * are normotensive volunteers.

  In humans, as in animal experiments, the functional water of the present invention reduced diastolic and systolic blood pressure by 10 to 18%.

Claims (9)

Functional water containing fine bubbles generated by aeration of one or more gases selected from the group consisting of air, hydrogen, oxygen and nitrogen, and having hydrogen peroxide removal ability. Functional water containing fine bubbles generated by aeration of one or more gases selected from the group consisting of air, hydrogen, oxygen, and nitrogen through a microfiltration membrane, an ultrafiltration membrane, or a gas separation membrane. The functional water according to claim 2, which has hydrogen peroxide removing ability. Functional water according to any one of claims 1 to 3, for the treatment of metabolic syndrome, adiponectin, leptin, TNF-α or diseases or conditions associated with oxidative disorders, or hypertension. Antioxidant functional water containing fine bubbles generated by aeration of one or more gases selected from the group consisting of air, hydrogen, oxygen and nitrogen. A food composition, cosmetic composition or pharmaceutical composition comprising the functional water according to claim 5. A pharmaceutical composition for the treatment of metabolic syndrome, adiponectin, leptin, TNF-α or a disease or condition associated with oxidative disorder, or hypertension, comprising the functional water according to claim 5. The functional water according to any one of claims 1 to 3, wherein air is contained at least 50 times the theoretical dissolved value. The functional water according to any one of claims 1 to 3, wherein hydrogen is contained at least 10 times the theoretical dissolved value.