JP2007077088A - Physiologic saline and method for production of the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide physiologic saline containing atomic hydrogen in large quantity, having -400 to -600 mV of oxidation-reduction potential, and 4.5-8.0 of pH. <P>SOLUTION: The physiologic saline is obtained by infusing hydrogen gas into an aqueous solution of sodium chloride of 0.9% concentration, under 0.1-0.95 MPa of infusing pressure for 10 sec to 10 min to form bubbles of molecular hydrogen and then contacting the bubbles of molecular hydrogen with elements of the platinum group for activating the molecular hydrogen and converting into atomic hydrogen. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a novel physiological saline and a method for producing the same. More specifically, the present invention relates to a physiological saline containing a large amount of atomic hydrogen, having a redox potential of -400 mV to -600 mV, and a pH of 4.5 to 8.0, and a method for producing the same.

  The Japanese Pharmacopoeia says “physiological saline”, “this product is an aqueous injection and contains 0.85 to 0.95% sodium chloride (NaCl: 58.44). Dissolve 9 g in an appropriate amount of water for injection to make a total volume of 1000 mL, and manufacture by injection manufacturing method.No preservative is added to this product.The property of this product is a colorless transparent liquid with a weak salty pH. Is 4.5 to 8.0 ", and no other detailed regulations or regulations are described.

  In response, various saline solutions containing additives have been developed and marketed. For example, in the past, heparin saline was used in hospitals with heparin sodium injection in physiological saline and diluted 10 to 100 times. However, from Terumo Corporation, heparin saline was used as a syringe in advance. So-called “heparin-containing physiological saline” has been proposed which reduces the risk of bacterial contamination during filling, adjustment and storage.

  However, research and development have not yet been conducted on physiological saline focusing on the redox potential of organs in the body, particularly body fluids. The redox reaction of human organs or in vivo reactions has a low potential, usually in the range of −100 mV to −400 mV, and the pH is in the range of 3 to 7. It is said that when the oxidation-reduction potential of the body fluid increases, active oxygen tends to stay and damage the organ. In particular, the intestines where the intestinal microorganisms actively act to digest and absorb nutrients must be maintained in an anaerobic reducing atmosphere.

For example, the redox potential of (acetic acid + CO ₂ + 2H ⁺ / α-ketoglutaric acid reaction) is −673 mV, and the redox potential of (acetic acid + CO ₂ / pyruvic acid reaction) is −699 mV, (acetic acid + 2H ⁺ / acetaldehyde) in vivo. The redox potential of (reaction) is −581 mV, the redox potential of ferredoxin is −413 mV, the redox potential of (xanthine + H ⁺ / hypoxanthine + H ₂ O) is −371 mV, and the oxidation of (uric acid + H ⁺ / xanthine + H ₂ O). The reduction potential is −360 mV, and the redox potential of (acetoacetic acid + 2H ⁺ / β-hydroxybutyric acid reaction) is −346 mV (cystine + 2H ⁺ / 2 cysteine reaction) is −340 mV.

  Thus, the reactions of enzymes, coenzymes, and metabolism-related substances in the living body are in an environment where the redox potential is low. In addition, water or food having a low redox potential has an action of separating and eliminating active oxygen that oxidizes the body and molecules or atoms having one or more unpaired electrons, that is, free radicals, It is said to promote the reaction of an active oxygen scavenging enzyme called SOD (superoxide dismutase).

  By the way, the redox potential of tap water is +400 to +800 mV, and the pH is in the range of 6.5 to 8. Therefore, it is considered that tap water cannot be balanced with a living organ having a redox potential in the range of −100 mV to −400 mV.

  Body fluids provide a place for metabolic reactions in the body, including redox reactions. Body fluids occupy almost 60% of the living body. Body fluids are composed mainly of water, and electrolytes, proteins, and the like as important components. This is the reason why water having a low redox potential is effective in vivo.

  The elements constituting the human body are 66.0% oxygen, 17.5% carbon, 10.2% hydrogen, 2.4% nitrogen, and 96.1% in total, and the rest is mineral. Substances produced by oxygen, carbon, hydrogen, and nitrogen are water and organic compounds. About 60% of body weight is occupied by water for human boys and about 50% for girls.

  And about 2/3 of the amount of water in the body exists in the cell and is called intracellular fluid. On the other hand, the remaining 1/3 exists outside the cell and is called extracellular fluid. 1/3 of the extracellular fluid is blood water (plasma) and 2/3 is tissue fluid. In addition, there are small amounts of cerebrospinal fluid, joint fluid, and lymph.

  Therefore, if the redox potential of physiological saline that is mainly instilled into blood vessels and mixed with blood is also maintained within the range of −400 mV to −600 mV, which is the redox potential of the in vivo reaction described above, It is considered preferable from the viewpoint of biocompatibility.

  On the other hand, when considering physiological saline in terms of the action of removing active oxygen in the living body, as described above, the redox reaction of the human organ or in vivo reaction has a low potential and is usually from −100 mV to −400 mV. Since it is within the range, it is said that when the redox potential of the body fluid increases, active oxygen tends to stay and damage the organ.

All causes of the generation of free radicals such as active oxygen in the living body have not been completely elucidated. However, as one of them, for example, when the skin is irradiated with ultraviolet rays, it acts on water molecules existing inside and outside the cells constituting the skin to generate positive and negative water molecule ions. These ions are then further decomposed H ^+, OH ^- in addition to the stable ions, to produce a OH ·, free radicals H ·. When there is no reactant, between these free radicals, OH · + H · → H ₂ O (water), H · + H · → H ₂ (hydrogen gas), OH · + OH · → H ₂ O ₂ (excess Reaction such as hydrogen oxide occurs.

By the way, OH., H., etc. free radicals have unpaired electrons in the outermost orbital, so that the electron spin remains without being erased. That is, the spin angular motion is not zero and exhibits various magnetic properties. For example, molecules in which all electrons are paired show diamagnetism, while those with unpaired electrons show paramagnetism. Usually, free radicals are highly reactive because they attempt to bind and stabilize electron pairs with other unpaired electrons. Therefore, when there are reactive substances in the surroundings as in the living body, OH ·, H ·, H ₂ O ₂ react with them, and as a result, various abnormal phenomena occur in the living body. For example, when acting on DNA, it causes deamination, dehydrogenation, breakage of base bonds, cleavage of bases, oxidation of sugars, release of inorganic phosphorus, etc., causing various diseases.

Next, theoretical considerations will be described regarding the elimination method of free radicals. The living body is not an exception to the laws of thermodynamics, and changes in free energy (Gibbs free energy) as a measure of energy for work, that is, ΔG = ΔH−TΔS (ΔH is enthalpy change, T is absolute temperature, ΔS The change (unit J) represented by the entropy change is the starting point of bioenergy. Most of the free energy production in the living body depends on the free energy released by the difference in the redox potential of the reactant in the redox reaction rather than the concentration change in nature. Here, oxidation is a reaction for losing electrons, and reduction is a reaction for obtaining electrons. For example, the reaction of 1 / 2H ₂ + Fe ³⁺ ⇔H ⁺ + Fe ^{2+ is} an oxidation reaction of 1 / 2H ₂ −e → H ⁺ (or 1 / 2H ₂ → H ⁺ + e) and Fe ³⁺ + e → Fe ^2+. It can be divided into reduction reactions. In this case, ½H _{2 that} is oxidized, that is, loses electrons and gives to others acts as a reducing agent, and Fe ³⁺ that is reduced, that is, receives electrons, acts as an oxidizing agent. In general, the oxidation-reduction reaction of AH + B⇔A + BH by the transfer of hydrogen can also be considered by decomposing into an oxidation reaction of AH → A + H ⁺ + e and a reduction reaction of B + H ⁺ + e → BH. Transfer of hydrogen can be regarded as transfer of electrons H ⁺ + e. In this way, the movement of electrons and the movement of hydrogen can be regarded as equivalent.

In view of this, in order to eliminate free radicals such as active oxygen, it is only necessary to stabilize them by reducing them with atomic hydrogen (H H ⁺ + e).

  When the above is reviewed, it is understood that it is preferable that the physiological saline injected into the blood also has the ability to reduce the degree of oxidative stress due to active oxygen generated in the blood. This capability requires the requirement that the redox potential of physiological saline is in the range of -400 mV to -600 mV and that a large amount of atomic hydrogen is contained rather than molecular.

  Although there are still few inventions targeting the redox potential of physiological saline, Patent Document 1 discloses that 0.1 to 1000 atmospheres of hydrogen gas at −180 to 90 ° C. is applied to physiological saline at 0 to 100 ° C. A physiological saline having an oxidation-reduction potential of −10 mV or less and −2000 mV or more is disclosed by pressurizing and dissolving the solution at normal temperature and normal pressure.

  However, in the invention described in Patent Document 1, the hydrogen blown into the physiological saline is not atomic hydrogen but the total amount is molecular hydrogen. Therefore, the physiological saline described in Patent Document 1 has no ability to eliminate free radicals such as active oxygen in blood vessels. Moreover, since patent document 1 has not demonstrated the theoretical explanation and effect by setting the oxidation-reduction potential of physiological saline to -10 mV or less and -2000 mV or more, what kind of industrial applicability is there? It is unknown.

Patent Document 2 describes raw material water, silica-based quartz porphyry, alkali metal, magnesium, calcium, aluminum, zinc, and other metals having high electronegativity, or iron (II), tin (II), titanium (III), An apparatus for producing hydrogen water by bringing hydrogen into contact with a catalyst supporting a reducing metal in a low valence state such as chromium (II) is disclosed. However, the reducing metal disclosed in Patent Document 2 has a weak catalytic action for converting molecular hydrogen into atomic hydrogen.
JP-A-2005-53882 JP-A-2005-177724

  Accordingly, the problem to be solved by the invention is to provide a physiological saline containing a large amount of atomic hydrogen, having a redox potential of -400 mV to -600 mV, and a pH of 4.5 to 8.0.

Another problem to be solved by the invention is to provide a method for producing a physiological saline containing a large amount of atomic hydrogen, having a redox potential of -400 mV to -600 mV, and a pH of 4.5 to 8.0. That is.
Other problems and advantages to be solved by the invention will be clarified in the following.

The present inventor does not like to be bound by theory, but in order to formulate means for solving the problem, the following theoretical consideration was made with respect to generation of free radicals, action thereof, and elimination. All causes of the generation of free radicals such as active oxygen in the living body have not been completely elucidated. However, as one of them, for example, when the skin is irradiated with ultraviolet rays, it acts on water molecules existing inside and outside the cells constituting the skin to generate positive and negative water molecule ions. These ions are then further decomposed H ^+, OH ^- in addition to the stable ions, to produce a OH ·, free radicals H ·. When there is no reactant, between these free radicals, OH · + H · → H ₂ O (water), H · + H · → H ₂ (hydrogen gas), OH · + OH · → H ₂ O ₂ (excess Reaction such as hydrogen oxide occurs. By the way, OH., H., etc. free radicals have unpaired electrons in the outermost orbital, so that the electron spin remains without being erased. That is, the spin angular motion is not zero and exhibits various magnetic properties. For example, molecules in which all electrons are paired show diamagnetism, while those with unpaired electrons show paramagnetism. Usually, free radicals are highly reactive because they attempt to bind and stabilize electron pairs with other unpaired electrons. Therefore, when there are reactive substances in the surroundings as in the living body, OH ·, H ·, H ₂ O ₂ react with them, and as a result, various abnormal phenomena occur in the living body. For example, when acting on DNA, it causes deamination, dehydrogenation, breakage of base bonds, cleavage of bases, oxidation of sugars, release of inorganic phosphorus, etc., causing various diseases.

Next, theoretical considerations will be described regarding the elimination method of free radicals. The living body is not an exception to the laws of thermodynamics, and changes in free energy (Gibbs free energy) as a measure of energy for work, that is, ΔG = ΔH−TΔS (ΔH is enthalpy change, T is absolute temperature, ΔS The change (unit J) represented by the entropy change is the starting point of bioenergy. Most of the free energy production in the living body depends on the free energy released by the difference in the redox potential of the reactant in the redox reaction rather than the concentration change in nature. Here, oxidation is a reaction for losing electrons, and reduction is a reaction for obtaining electrons. For example, the reaction of 1 / 2H ₂ + Fe ³⁺ ⇔H ⁺ + Fe ^{2+ is} an oxidation reaction of 1 / 2H ₂ −e → H ⁺ (or 1 / 2H ₂ → H ⁺ + e) and Fe ³⁺ + e → Fe ^2+. It can be divided into reduction reactions. In this case, ½H _{2 that} is oxidized, that is, loses electrons and gives to others acts as a reducing agent, and Fe ³⁺ that is reduced, that is, receives electrons, acts as an oxidizing agent. In general, the oxidation-reduction reaction of AH + B⇔A + BH by the transfer of hydrogen can also be considered by decomposing into an oxidation reaction of AH → A + H ⁺ + e and a reduction reaction of B + H ⁺ + e → BH. Transfer of hydrogen can be regarded as transfer of electrons H ⁺ + e. In this way, the movement of electrons and the movement of hydrogen can be regarded as equivalent.

  By the way, Kyoritsu Shuppan Co., Ltd. published “Chemical Dictionary 2”, “Active hydrogen”, “Discharge, high heat, and ultraviolet rays cause the stable covalent bond of hydrogen molecules to break, and atomic hydrogen is generated, so chemical reactions are likely to occur. In addition, hydrogen on the reduction catalyst such as so-called nascent hydrogen and palladium or nickel is considered to be in an atomic state or a state close to it, and is highly reactive. It is defined as “included” and explains that it exhibits a strong reducing action.

Many biological reactions involve oxidation-reduction reactions and play an extremely important role in metabolic reactions and the like. In addition, in a system (solution) containing an oxidant and a reductant, not limited to a living body, an inactive electrode that itself does not participate in the oxidation-reduction reaction, such as platinum, is immersed in the solution. Appears. This potential difference is an oxidation-reduction potential (Oxidation-Reduction Potential = ORP), and the unit is expressed in mV. Now, when the activity of an oxidant of a certain substance is represented as [Ox] and the activity of a reductant is represented as [Red], the mixed state of both is represented by the formula (1).
[Ox] + ne → [Red] (1)
(E is an electron, n is the number of moving electrons)
The oxidation-reduction potential (EmV) of the electrode reaction equation represented by (1) is represented by the Nernst equation (2).
E = E ₀ + (RT / nF) ln [Ox] / [Red] (2)

In the formula (2), R is a gas constant (8.31 Jmol ⁻¹ K ⁻¹ ), T is an absolute temperature (K), and F is a Faraday constant (96406 JV ⁻¹ ). E ₀ is a standard redox potential when [Ox] = [Red].

  In equation (2), ln [Ox] / [Red] is a natural logarithm. Therefore, the negative (−) value of the oxidation-reduction potential E can be increased as the denominator, that is, [Red] is made extremely larger than the numerator, that is, [Ox]. That is, theoretically, the greater the activity of the reductant [Red] than the activity of the oxidant [Ox], the more the redox potential can be made negative (−) value. Therefore, in the method of reducing the oxidation-reduction potential of the raw material water to a negative potential by blowing hydrogen into the raw material water in a mixed state of the oxidant and the reductant, the activity of the reductant [Red] is changed to the oxidant [Ox]. It is to make it larger than the activity. In this case, it is preferable to blow raw material water in a mixed state of an oxidant and a reductant with a platinum group element as a catalyst because efficiency is improved.

Therefore, the present inventor studied that as much hydrogen as possible was blown into a 0.9% sodium chloride aqueous solution to be dissolved and contacted with a platinum group element. Simply blowing hydrogen into a 0.9% sodium chloride aqueous solution to dissolve it is molecular hydrogen (H ₂ ), not atomic hydrogen (H). There is no ability to do. Therefore, the present invention is to inject hydrogen gas into a 0.9% sodium chloride aqueous solution and bring it into contact with a platinum group element in situ to reduce active radicals such as active oxygen. It is intended.

  In the present invention, the method of injecting hydrogen gas bubbles into a 0.9% sodium chloride aqueous solution is not particularly limited. For example, the hydrogen water production apparatus described in Japanese Patent Application No. 2003-436591 filed by one of the inventors can be used. This outline will be described. If a large-capacity hydrogen cylinder is used as the hydrogen supply apparatus, it can be used as an industrial large-scale production apparatus, but if a cylinder with a hydrogen filling pressure of 0.98 MPa or less is used, the range of use for small-scale production such as hospitals and homes Expands. The hydrogen gas injection pressure varies depending on the scale of the apparatus. For example, if the hydrogen gas injection pressure is in the range of 0.1 to 0.95 MPa, a redox potential of −550 mV and a dissolution of 0.5 mg / l. The amount of hydrogen can be secured. The injection time of hydrogen gas is, for example, in the range of 10 seconds to 10 minutes, preferably 2 to 5 minutes. If the injection time of hydrogen gas is within this range, a redox potential of -620 mV and a dissolved hydrogen amount of 1.5 mg / l can be secured. If the injection time of hydrogen gas is too short, the potential is unstable. If it is too long, the potential lowering effect is not particularly affected, and the cost is increased.

  When hydrogen gas is injected into a 0.9% sodium chloride aqueous solution, a hydrogen gas bubble having a uniform diameter is formed using a pore membrane having a predetermined pore size, and the 0.9% sodium chloride aqueous solution is formed. Solubility, residence time in water, and the like can be improved. At this time, care must be taken to prevent hydrogen bubbles from becoming nano-sized. This is because when the hydrogen bubble becomes nano-sized, the surface of the bubble may become charged and become free radicals.

  The raw material water for producing the 0.9% sodium chloride aqueous solution used in the present invention is water for injection listed in the Japanese Pharmacopoeia, equivalent bacteria-filtered distilled water, ion-exchanged water and the like.

  The platinum group element used in the present invention will be described. Among the elements belonging to Group VIII of the Periodic Table, the platinum group element includes six elements of ruthenium (Ru), rhodium (Rh), palladium (Pd), osmium (Os), iridium (Ir), and platinum (Pt). It is a generic name. These platinum group elements are active in various reactions such as hydrogenation, dehydrogenation, and oxidation. It functions as a so-called reduction catalyst. Therefore, when molecular hydrogen comes into contact with a platinum group element, molecular hydrogen becomes atomic or in a state close thereto. Therefore, in this specification, the action of the platinum group element to bring molecular hydrogen into an atomic state or a state close thereto is called “catalytic action”.

  In the present invention, in order to improve the catalytic action of the platinum group element or increase the use efficiency, the platinum group element is used in the form of a platinum group element with a carrier carried on various supports or in the form of a net. Is preferred. Examples of the carrier include alumina, asbestos, activated carbon, silica gel, barium sulfate, calcium carbonate, and pumice.

  The platinum group element particularly preferably used in the present invention is platinum, and the shape thereof is platinum colloid, platinum black, or platinum sol. Catalytic activity is inversely proportional to the size of the particles, and is in the order of platinum colloid> platinum black> platinum sponge. Each will be described below.

  The platinum colloid particularly preferably used in the present invention is, for example, (1) reduced by applying a Bunsen burner flame to the surface of the hexachloroplatinum (IV) acid aqueous solution, and (2) protected by the hexachloroplatinum (IV) acid aqueous solution. Add sodium ascorbate, gum arabic, or gelatin as a colloid and reduce with a reducing agent such as hydrazine. (3) Put pure water into the evaporating dish and cool it between two platinum wires immersed in it. It is manufactured by a method such as a Bledich method in which an arc is discharged. The platinum colloid produced by the Bredig method is unstable, but the catalytic ability is strong because the colloidal particles are not coated with a protective colloid. On the other hand, those containing protective colloids are stable although their catalytic ability is lower than that of platinum colloids produced by the Bredig method.

  Similarly, platinum black particularly preferably used in the present invention includes, for example, (1) heating an aqueous solution of hexachloroplatinic (IV) acid, neutralizing with sodium carbonate, and pouring it into a boiled sodium formate solution, ( 2) It is produced by a method in which an aqueous formaldehyde solution is added to an aqueous solution of platinum chloride (IV) or hexachloroplatinum (IV) acid, and an aqueous sodium hydroxide solution is gradually added while cooling. Further, when this platinum black is heated in a hydrogen stream, the platinum fine particles are half melted to form a platinum sponge.

Therefore, the above problem can be solved by the means described below.
1. A physiological saline containing a large amount of atomic hydrogen, having a redox potential of -400 mV to -600 mV, and a pH of 4.5 to 8.0.

2. In the item 1, the amount of atomic hydrogen is 1.5 mg / L.

3. A step of generating molecular hydrogen bubbles by injecting hydrogen gas into a 0.9% sodium chloride aqueous solution with an injection pressure of 0.1 to 0.95 MPa and an injection time of 10 seconds to 10 minutes, and molecules A large amount of atomic hydrogen including a step of bringing molecular hydrogen into contact with a platinum group element and bringing it into contact with a platinum group element to convert it into atomic hydrogen, and a redox potential of -400 mV to -600 mV, pH Manufacturing a physiological saline having a pH of 4.5 to 8.0.

4). In the above item 3, the amount of atomic hydrogen is 1.5 mg / L.

  According to the invention of claim 1, the physiological saline contains a large amount of atomic hydrogen, the oxidation-reduction potential is -400 mV to -600 mV, and the pH is 4.5 to 8.0. -Affinity) is good, and the degree of oxidative stress due to active oxygen generated in blood, creatinine, blood urinary nitrogen amount and the like can be reduced.

  According to the invention of claim 2, since the amount of atomic hydrogen is 1.5 mg / L, the oxidation-reduction potential immediately after the production can be maintained even after 168 hours have passed since the production.

  According to the invention of claim 3, physiological saline containing a large amount of atomic hydrogen, having a redox potential of -400 mV to -600 mV, and a pH of 4.5 to 8.0 is efficiently reproduced with almost 100% reproduction. It can be manufactured with good characteristics.

  According to the invention of claim 4, since the amount of atomic hydrogen is 1.5 mg / L, the oxidation-reduction potential immediately after the production can be maintained even after 168 hours have passed since the production.

  Hereinafter, the effects of the present invention will be clarified by describing examples.

[Preparation of aqueous sodium chloride solution]
A final sodium chloride aqueous solution for physiological saline was prepared by dissolving 9 g of (NaCl: 58.44) in water for injection (distilled water) to a total volume of 1000 mL according to the description in the Japanese Pharmacopoeia. This sodium chloride aqueous solution had an Na ⁺ equivalent of 154 meq / L and a Cl ⁻ equivalent of 155 meq / L.

[Preparation of physiological saline]
In the hydrogen water production apparatus described in Patent Document 2, the catalyst was used in place of the one obtained by spreading platinum colloid on alumina. 3 L of the above sodium chloride aqueous solution is sealed in a reaction tank having a storage capacity of 5 L, and an injection pressure of 0.35 MPa and a flow rate of 0 from a hydrogen cylinder (hydrogen: 99.99 VOL%) conforming to the Food Sanitation Law manufactured by Iwatani Gas Co., Ltd. A total amount of 2.5 L of hydrogen gas was injected at 5 L / min in 5 minutes to prepare the desired physiological saline.

[Sealing in saline container]
The physiological saline prepared in this manner was used in a container described in JP-A-2005-901, for example, the outermost layer was a biaxially stretched polyethylene terephthalate film (thickness: 12 μm), and the intermediate layer was an aluminum foil (thickness). : 9 μm), and the innermost layer was filled with a special polyester film (thickness: 40 μm) in a three-layer structure with a capacity of 300 mL, which is a variable volume container (aluminum pouch).

[Sterilization of sealed saline]
The physiological saline thus sealed was boil sterilized in hot water at 85 ° C. for 30 minutes.

[Performance measurement of physiological saline]
Table 1 shows the results obtained by measuring the redox potential (unit: mV), pH, amount of dissolved hydrogen, and water temperature (° C.) of the physiological saline thus prepared.

  For measurement of the oxidation-reduction potential, “Portable ORP Meter RM-20P” (registered trademark) manufactured by Toa DKK Industry Co., Ltd. was used.

  For the measurement of pH, “Portable pH Meter HM-20P” (registered trademark) manufactured by Toa DKK Industry Co., Ltd. was used.

  To measure the amount of dissolved hydrogen, “DHD1-1 type dissolved hydrogen meter” (registered trademark) manufactured by Toa DKK Industry Co., Ltd. was used.

[Measurement of free radical scavenging ability]
1. Measuring equipment used: Hitachi spectrophotometer Reagents used 2-1: Source of free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) was used as a free radical model. DPPH is a relatively stable free radical having a structure represented by the following chemical formula 1, but easily binds to other free radicals, so the presence of free radicals generated by heat, radiation, etc., concentration It is used to determine In the present invention, the free radical scavenging functional water of the present invention is used as a measure of the free radical scavenging ability by measuring the ability of scavenging free radicals generated by DPPH.

2-2: Preparation of DPPH solution 2-2-1: 100 μM-DPPH (50% ethyl alcohol solution)
0.0010 g of DPPH was precisely weighed and placed in a 50 mL volumetric flask that was shielded from light with aluminum foil. Next, about 25 mL of 99% ethanol was added and dissolved. After complete dissolution, the total volume was made up to 50 mL with ultrapure water. During the melting operation, the measuring flask was completely shielded from light.
2-2-2: 25 μM-DPPH (50% ethyl alcohol solution)
3 mL of 100 μM DPPH solution (50% ethyl alcohol solution) was taken and added to 9 mL of 50% ethanol.
2-3: Platinum colloid solution Platinum (Pt) -PVP (polyvinylpyrrolidone) colloid (4.0 wt%) was diluted 100 times with ultrapure water.

[Measuring method]
2 mL of the 25 μM-DPPH solution and 2 mL each of the physiological saline solution, tap water, and ultrapure water prepared in Example 1 were mixed in a test tube using a vortex mixer, and Pt diluted 100 times 15 seconds before measurement. -10 μL of PVP colloid was added and stirred, and the absorbance was measured at a wavelength of 520 nm.

[Measurement result]
The absorbance measurement results at 520 nm of the test water used in Example 1, Reference Example, and Control Example are shown in Table 2.

[Discussion]
In Example 1 to which the Pt-PVP colloid solution was added, immediately after the addition of the Pt-PVP colloid solution, the purple color of the DPPH radical faded and the diphenylpicrylhydrazine changed to yellow. On the other hand, in the case of Fukuyama city tap water (clean water) and ultrapure water, the color did not fade immediately after the addition of the Pt-PVP colloidal solution, but faded after about 5 to 6 minutes. As a result of several experiments, it was confirmed that 2 mL of hydrogenated water and 10 μL of Pt-PVP colloid solution can completely eliminate radicals in 2 mL of 25 μM-DPPH solution.

  From the above results, the hydrogen blown into the physiological saline of Example 1 exists in a molecular state in water, but when a platinum colloid exists, the molecular state hydrogen is activated, and it is atomic or It was confirmed that the radicals of DPPH can be completely erased due to the close to atomic state. This is due to the fact that "active hydrogen is a chemical reaction because active hydrogen is generated by atomic hydrogen generation by breaking stable covalent bonds of hydrogen molecules due to discharge, high heat, and ultraviolet rays," published by Kyoritsu Publishing Co., Ltd. Hydrogen that is easily generated, and so-called nascent hydrogen and hydrogen on the reduction catalyst, such as palladium and nickel, are considered to be in an atomic state or a state close to it, and are highly reactive. Included in hydrogen. ”

[IN VIVO TEST1]
Using the physiological saline prepared in the Examples, the degree of reduction in oxidative stress due to active oxygen, the degree of reduction in creatinine, and the degree of reduction in blood urine nitrogen were measured.

[Measurement of reduction in oxidative stress]
Blood hydroperoxide was measured. In other words, when the colored liquid chromogen (N, N-diethylparaphenylenediamine) is oxidized by a free radical, it becomes a colorless to reddish purple cation. This cation is measured with a photometer to quantify hydroperoxide. It was measured.

[Dosage schedule]
(1) Administration animal group group 1: 4 healthy cats 6 months, 8 months, 10 months and 12 months after birth.
Group 2: Four healthy cats 14 months, 16 months, 18 months, and 20 months old.
Group 3: 4 healthy cats 36 months, 42 months, 48 months, 54 months old.
Group 4: 4 healthy cats 60 months, 66 months, 72 months and 108 months old.

  Blood was collected from each group of cats, and the hydroperoxide in the blood before physiological saline administration was measured. Subsequently, the physiological saline prepared in Example 1 was administered by intravenous injection at a dose of 1 mL / kg. Ten minutes after intravenous administration, blood was collected and the hydroperoxide in the blood was measured. The average value of each measured value of hydroperoxide in blood before and after physiological saline administration was taken and listed in Table-3.

  The measured value of hydroperoxide in blood is 250-300 U. Although the range of CARR is a normal value, it is apparent that the physiological saline of Example 1 is administered and is about 6 to 11% lower than before administration. From this result, it is clear that atomic hydrogen contained in the physiological saline of the present invention significantly contributes to the reduction of oxidative stress.

[IN VIVO TEST2]
[Measurement of blood urine nitrogen]
Using the physiological saline prepared in Example 1, the blood urine nitrogen of physiological saline for cats with chronic renal failure was measured.

  About half of residual nitrogen in healthy human plasma, 9-18 mg / 100 mL is nitrogen as urea, and urine occupies 80% or more of total excreted nitrogen. The amount of urea nitrogen, especially urinary excretion, varies greatly depending on the protein content in the diet. In kidney disease with urea excretion disease, the amount of urea nitrogen in the blood increases. Therefore, it is possible to know the severity of kidney disease by measuring the amount of urinary nitrogen.

[Dosage schedule]
(1) Administered animal group group 1: 4 cats with chronic renal failure 6 months, 8 months, 10 months, 12 months old.
Group 2: Four cats with chronic renal failure 14 months, 16 months, 18 months, and 20 months old.
Group 3: 4 cats with chronic renal failure 36 months, 42 months, 48 months, 54 months old.
Group 4: 4 cats with chronic renal failure 60 months, 66 months, 72 months, 108 months old.

  Blood was collected from each group of cats and blood urine nitrogen before physiological saline administration was measured. Subsequently, the physiological saline prepared in Example 1 was administered by intravenous injection at a dose of 1 mL / kg. Ten minutes after intravenous administration, blood was collected and blood urine nitrogen was measured. The average value of each measured value of blood urine nitrogen before and after physiological saline administration was taken and listed in Table-4.

  As is clear from Table-4, it is clear that the amount of blood urine nitrogen was reduced by about 70 to 80% as compared to the pre-administration as a result of administration of the physiological saline of Example 1. From this result, it can be inferred that the atomic hydrogen contained in the physiological saline of the present invention and the low redox potential have some positive effects.

[IN VIVO TEST3]
[Measurement of creatinine]
Using the physiological saline prepared in Example 1, creatinine was measured for cats with chronic renal failure.

  Creatinine is contained in urine as a physiological metabolite of creatine in vivo. Creatine is synthesized in vivo from arginine, glycine, and methionine, and is abundant in muscle (98% of the whole) and mostly exists as creatylic acid, and plays a role of energy storage for muscle contraction. Slightly present in blood. It hardly appears in healthy male urine, but it appears slightly in the urine of women and children. Therefore, it can be said that the smaller the amount of creatinine in the urine, the closer it is to a healthy state.

[Dosage schedule]
(1) Administered animal group group 1: 4 cats with chronic renal failure 6 months, 8 months, 10 months, 12 months old.
Group 2: Four cats with chronic renal failure 14 months, 16 months, 18 months, and 20 months old.
Group 3: 4 cats with chronic renal failure 36 months, 42 months, 48 months, 54 months old.
Group 4: 4 cats with chronic renal failure 60 months, 66 months, 72 months, 108 months old.

  Urine was collected from each group of cats, and the amount of creatinine before physiological saline administration was measured. Subsequently, the physiological saline prepared in Example 1 was administered by intravenous injection at a dose of 1 mL / kg. Ten minutes after intravenous administration, urine was collected to measure the amount of creatinine. The average value of the amount of creatinine before and after physiological saline administration was taken and listed in Table-5.

  As is clear from Table-5, as a result of administering the physiological saline of Example 1, it is clear that the amount of creatinine was reduced by about 19 to 30% from before administration. From this result, it can be inferred that the atomic hydrogen contained in the physiological saline of the present invention and the low redox potential have some positive effects.

  As described above, the physiological saline of the present invention contains a large amount of atomic hydrogen of 1.315 mg / L immediately after production and 0.747 mg / L after 168 hours, and has a redox potential. Since −400 mV to −600 mV and pH is 4.5 to 8.0, there is industrial applicability exemplified below.

1. When the living body is irradiated with ultraviolet rays, positive and negative water molecule ions are generated by acting on water molecules present in blood vessels that are part of the living body. These ions are then further decomposed H ^+, OH ^- in addition to the stable ions, to produce a OH ·, free radicals H ·. When there is no reactant, between these free radicals, OH · + H · → H ₂ O (water), H · + H · → H ₂ (hydrogen gas), OH · + OH · → H ₂ O ₂ (excess Reaction such as hydrogen oxide occurs. By the way, OH., H., etc. free radicals have unpaired electrons in the outermost orbital, so that the electron spin remains without being erased. That is, the spin angular motion is not zero and exhibits various magnetic properties. For example, molecules in which all electrons are paired show diamagnetism, while those with unpaired electrons show paramagnetism. Usually, free radicals are highly reactive because they attempt to bind and stabilize electron pairs with other unpaired electrons. Therefore, when there are reactive substances in the surroundings as in the blood vessel, OH., H., H.sub.2O.sub.2 reacts with them, and as a result, various abnormal phenomena occur. For example, when acting on DNA, it causes deamination, dehydrogenation, breakage of base bonds, cleavage of bases, oxidation of sugars, release of inorganic phosphorus, etc., causing various diseases. However, when the physiological saline of the present invention is administered to mammals including humans at a dose of 1 mL / kg according to a predetermined administration schedule, plasma free radicals are eliminated, and as a result, the degree of oxidative stress due to active oxygen is reduced. descend. This was verified by measuring the amount of hydroperoxide. Therefore, it can be used as a new physiological saline.

2. When the physiological saline of the present invention is administered to mammals with chronic renal failure including humans at a dose of 1 mL / kg according to a predetermined administration schedule, it is effective in alleviating chronic renal failure. This was verified by the measurement of blood urine nitrogen. Therefore, it can be used as a new physiological saline.

3. When the physiological saline of the present invention is administered at a dose of 1 mL / kg to mammals including chronic renal failure including humans according to a predetermined administration schedule, the amount of urinary creatinine is reduced. This was verified by measuring the blood urine creatinine level. Therefore, it can be used as a new physiological saline.

Claims (4)

A physiological saline containing a large amount of atomic hydrogen, having a redox potential of -400 mV to -600 mV, and a pH of 4.5 to 8.0. The physiological saline solution according to claim 1, wherein the amount of atomic hydrogen is 1.5 mg / L. A step of injecting hydrogen gas into a 0.9% sodium chloride aqueous solution at an injection pressure of 0.1 to 0.95 MPa and an injection time of 10 seconds to 10 minutes to generate molecular hydrogen bubbles, and molecular hydrogen A large amount of atomic hydrogen including a step of bringing molecular hydrogen into contact with platinum group elements to activate molecular hydrogen to convert it into atomic hydrogen, a redox potential of −400 mV to −600 mV, and a pH of 4 A method for producing a physiological saline solution of 5 to 8.0. The method for producing a physiological saline solution according to claim 3, wherein the amount of atomic hydrogen is 1.5 mg / L.