JP2005232094A - Ozone dissolved glycerol solution, ozone dissolved glycerol solidified material and ozone dissolved mixed solution, method for producing ozone dissolved glycerol solution, method for producing ozone dissolved mixed solution and method for preserving ozone dissolved glycerol solution - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To prepare an ozone dissolved glycerol solution and an ozone dissolved mixed solution keeping ozone concentration enough to exhibit sterilization effect and wound-healing effect for a long period and not generating harmful oxide (peroxide). <P>SOLUTION: The ozone dissolved glycerol solution can keep ozone concentration enough to exhibit sterilization effect for a long period, because ozone is dissolved in an amount of ≥400 ppm in ≥75% nonoxidative glycerol solution. Irritation due to glycerol can be suppressed by mixing the ozone dissolved glycerol solution with either one of vaseline and polyethylene glycol. The ozone dissolved mixed solution not losing oxidative force and not containing harmful oxide (peroxide) can be produced by mixing the ozone dissolved glycerol solution with either one of water, vaseline and polyethylene glycol under stirring. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to an ozone-dissolved glycerin solution, an ozone-dissolved glycerin solidified product, an ozone-dissolved mixed solution, a method for producing an ozone-dissolved glycerin solution, a method for producing an ozone-dissolved mixed solution, and a method for storing an ozone-dissolved glycerin solution.

  Various studies have demonstrated that ozone has a strong oxidizing action and is useful for sterilization. As a general method for producing gaseous ozone, there is a method in which a part is ozonized by discharging to air.

  In addition to gaseous ozone, ozone water in which ozone is dissolved in water is also used. Ozone water is produced by a method of dissolving ozone produced by discharging air into water by some method, or by directly electrolyzing water using an electrode having an ozone generation catalyst function, such as platinum, to generate oxygen. Some of them are ozonized and immediately dissolved in water.

In addition, a gas containing ozone having a concentration of 0.01 to 500 ppm is generated by an ozone generator, and dissolved or microbubbled into a liquid having a viscosity of 1 to 10 ⁶ Pa · s, and sealed into an ozone-containing viscous body. It has been known. Gaseous ozone and ozone water have no fixability, so their use has been limited. However, ozone can be fixed to a specific site as a cream or paste by using ozone-containing viscous material (Patent Document 1). reference).
Japanese Patent Laid-Open No. 10-139645

By the way, since there are many oxides (organic matter, blood, etc.) that use ozone in the wound site that actually uses the ozone-containing viscous material as a bactericidal agent, it is necessary that high-concentration ozone is dissolved. Yes, an ozone concentration of about 80 ppm is required as the final concentration. However, in the above ozone-sealed viscous body, a gas containing ozone having a concentration of 0.01 to 500 ppm is dissolved or microbubbled in a liquid having a viscosity of 1 to 10 ⁶ Pa · s. Was extremely low and was not suitable for practical use.

  Moreover, when the ozone concentration immediately after manufacture of an ozone enclosure viscous body is low, when the storage period became long, ozone concentration fell and it was not able to maintain the bactericidal effect. Further, depending on the type of the viscous material, there is a possibility that a harmful oxide (peroxide) is generated by being oxidized by ozone.

  An object of the present invention is to maintain an ozone concentration sufficient to exert a bactericidal effect and a wound healing effect for a long period of time, and an ozone-dissolved glycerin solution and an ozone-dissolved glycerin solidified product that do not generate harmful oxides (peroxides). An ozone-dissolved mixed solution, a method for producing an ozone-dissolved glycerin solution, a method for producing an ozone-dissolved mixed solution, and a method for storing an ozone-dissolved glycerin solution.

  In order to solve the above-mentioned problems, the invention described in claim 1 is an ozone-dissolved glycerin solution, characterized in that ozone is dissolved in a non-oxidized glycerin solution of 75% or more in an amount of 400 ppm or more.

  According to the first aspect of the present invention, since ozone is dissolved in high concentration in non-oxidized glycerin, it is possible to maintain an ozone concentration sufficient for exhibiting a bactericidal effect for a long period of time.

  The invention according to claim 2 is an ozone-dissolved mixed solution, wherein the ozone-dissolved glycerin solution according to claim 1 is mixed with any one of water, petrolatum, and polyethylene glycol, and ozone is dissolved at 80 ppm or more. It is characterized by.

  Since the high concentration of glycerin is irritating to the skin, it is necessary to reduce the concentration of glycerin when it is used in a lotion or a cosmetic liquid. By mixing the dissolved glycerin solution with any one of water, petrolatum, and polyethylene glycol, the irritability of glycerin can be suppressed. Moreover, since ozone is dissolved 80 ppm or more, sufficient sterilizing ability can be exhibited.

  In addition, when glycerin is added to ozone water after dissolving ozone in water, the oxidizing power disappears rapidly depending on the glycerin concentration, but after dissolving ozone in glycerin, the ozone-dissolved glycerin solution is diluted with water. But the oxidizing power is not lost.

  In addition, when petrolatum or polyethylene glycol is brought into gas-liquid contact with high-concentration ozone, harmful oxides (peroxides) are produced, but after dissolving high-concentration ozone in high-concentration glycerin, petrolatum or When mixed with polyethylene glycol, no harmful oxide (peroxide) is produced. Therefore, by mixing any one of water, petrolatum, and polyethylene glycol with the ozone-dissolved glycerin solution and stirring, the ozone-dissolved ozone is not lost and does not contain harmful oxides (peroxides). A mixed solution can be produced.

  Invention of Claim 3 is a manufacturing method of the ozone-dissolved glycerol solution of Claim 1, Comprising: Gas containing ozone is gas-liquid contacted to 75% or more of glycerol solutions, It is characterized by the above-mentioned.

  According to the invention described in claim 3, an ozone-dissolved glycerin solution in which ozone is dissolved at a high concentration in glycerin is produced by bringing gas containing ozone into gas-liquid contact with 75% or more of the glycerin solution. can do.

  Invention of Claim 4 is a manufacturing method of the ozone dissolved mixed solution of Claim 2, Comprising: The ozone dissolved glycerol solution manufactured with the manufacturing method of Claim 3, water, petrolatum, polyethyleneglycol Any one of the above is mixed and stirred.

  According to the invention described in claim 4, the same effect as that of the invention described in claim 2 can be obtained.

  The invention according to claim 5 is a method for preserving an ozone-dissolved glycerin solution, wherein the ozone-dissolved glycerin solution in which ozone is dissolved in a non-oxidized glycerin solution is refrigerated or frozen.

  Here, refrigerated storage is storage at −5 ° C. or higher and 10 ° C. or lower, and frozen storage is storage at −5 ° C. or lower. In addition, the glycerol density | concentration and ozone density | concentration of an ozone dissolved glycerol solution are arbitrary.

  According to the invention described in claim 5, the ozone concentration glycerin solution, in which ozone is dissolved in the non-oxidized glycerin solution, can be stored in a refrigerator for a long time by refrigerated storage or frozen storage. The concentration can be maintained.

  The invention according to claim 6 is an ozone-dissolved glycerin solidified product, wherein the ozone-dissolved glycerin solution in which ozone is dissolved in a non-oxidized glycerin solution is cooled and solidified.

  Here, the ozone-dissolved glycerin solidified product is an ozone-dissolved glycerin solution in a cooled and solidified state, and the glycerin may be crystallized and solidified, or becomes supercooled and the viscosity of the whole solution becomes high. It may be solidified. Further, glycerin may be solidified alone, or may be solidified with other components constituting the solution. In addition, the glycerol density | concentration and ozone density | concentration of an ozone dissolved glycerol solution are arbitrary.

  According to the invention described in claim 6, since the ozone-dissolved glycerin solution in which ozone is dissolved in the non-oxidized glycerin solution is cooled and solidified, the ozone concentration is less likely to be released than in the liquid state. Can be maintained at a high concentration for a longer period of time.

  According to the present invention, since high-concentration ozone is dissolved in the high-concentration glycerin solution, the dissolved concentration of ozone in the ozone-dissolved glycerin solution is maintained for a long time at a concentration sufficient to be used as a disinfectant or the like. be able to.

  Moreover, since the ozone-dissolved glycerin solution is mixed with water, petroleum jelly, or polyethylene glycol, it is possible to produce an ozone-dissolved mixed solution that does not lose its oxidizing power and does not contain harmful oxides (peroxides). it can.

  Further, by storing the ozone-dissolved glycerin solution in a refrigerated or frozen state, it is possible to maintain the ozone concentration at a high concentration for a long period of time compared with storing at normal temperature. Further, by cooling and solidifying the ozone-dissolved glycerin solution, ozone is less likely to be released than in a liquid state, and the ozone concentration can be maintained at a high concentration for a longer period.

  Hereinafter, embodiments of the present invention will be described in detail. The ozone-dissolved glycerin solution of the present invention can be produced by gas-liquid contact between a high-concentration glycerin solution and a gas having a high ozone concentration.

  A gas having a high ozone concentration can be produced by an ozone generator that generates ozone by silent discharge to oxygen gas, for example. When oxygen gas is used, a medical oxygen cylinder may be used, or oxygen gas produced by an oxygen generator may be used. When air is used, nitrogen oxides are produced. When a gas having a high ozone concentration is generated using air and the ozone concentration is measured by a potassium iodide titration method, the consumption of potassium iodide is apparently increased because of nitrogen oxides. Since nitrogen oxides are harmful substances, the method using air is not suitable for actual use.

  As the high-concentration glycerin solution, a glycerin solution having a glycerin concentration of 75% or more can be used, but 84 to 87% by weight of glycerin of the Japanese pharmacopoeia product is preferable, and the glycerin concentration of the Japanese pharmacopoeia product is 98% or more. More preferably, glycerin is used. Further, it is more preferable to use purified glycerin having a concentration of 98.5% or more. This is because if the glycerin concentration is high, ozone can be dissolved at a higher concentration.

  As a method for bringing a high-concentration glycerin solution into contact with a gas having a high ozone concentration, for example, a high-concentration (for example, 98% or more) glycerin solution is placed in a tank, and a high concentration of ozone is contained in the tank using an air diffuser. There is a method for releasing gas as fine bubbles. For example, an ozone-dissolved glycerin solution having an ozone concentration of about 3000 ppm can be produced by aeration of a gas having an ozone concentration of 80 g / kL (about 37000 ppm) in concentrated glycerin for about 7 days.

  The final concentration of ozone is determined depending on the glycerin concentration. In the case of the above-described method, the final concentration of ozone is about 400 ppm at a glycerin concentration of 75%, the final concentration of ozone is about 500 ppm at a glycerin concentration of 85%, and the final concentration of glycerin is 90%. When the final concentration of ozone is about 1000 ppm and the glycerol concentration is 98%, the final concentration of ozone is about 3000 ppm.

  The finally obtained ozone-dissolved glycerol solution preferably has a glycerol concentration of 75% or more and an ozone concentration of 400 ppm or more, more preferably a glycerol concentration of 80% or more and an ozone concentration of 500 ppm or more, and a glycerol concentration of 90% or more. The ozone concentration is more preferably 1000 ppm or more, and most preferably the glycerol concentration is 98% or more and the ozone concentration is 3000 ppm or more. This is because the higher the glycerin concentration, the higher the ozone concentration, the higher the bactericidal effect and the wound healing effect, and the longer the ozone concentration can be maintained. The ozone-dissolved glycerin solution produced in this way has a high initial concentration of ozone. As will be described later, the half-life of the ozone concentration becomes long, and the ozone concentration necessary as a disinfectant can be maintained over a long period of time. it can.

  Further, as can be seen from the long half-life of the ozone concentration, the amount of ozone released from this ozone-dissolved glycerin solution is extremely small. Therefore, ozone can be gradually released over a long period of time at the site where the ozone-dissolved glycerin solution is used and where it reaches. In addition, since the amount of ozone released is extremely small, this ozone-dissolved glycerin solution does not have an ozone odor at all even though high-concentration ozone is dissolved.

  In addition, the amount of ozone released from the ozone-dissolved glycerin solution can be further reduced by storing the ozone-dissolved glycerin solution refrigerated at -5 ° C. or higher and 10 ° C. or frozen at -5 ° C. or lower. It is possible to maintain the ozone concentration at a high concentration for a longer period of time.

  In particular, when the ozone-dissolved glycerin solution is cooled to obtain an ozone-dissolved glycerin solidified product, ozone is less likely to be released than the liquid state, and the ozone concentration can be maintained at a high concentration for a longer period. Here, the ozone-dissolved glycerin solidified product is an ozone-dissolved glycerin solution in a cooled and solidified state. The glycerin may be crystallized and solidified, and the viscosity of the entire solution is increased due to a supercooled state. May be. Further, glycerin may be solidified alone, or may be solidified with other components constituting the solution.

  Here, not only the ozone-dissolved glycerin solution having a glycerin concentration of 75% or more and an ozone concentration of 400 ppm or more, an ozone-dissolved glycerin solution of any concentration can be stored at a high concentration for a longer period of time by refrigerated storage or frozen storage. Can be maintained. The same applies to the case of cooling to obtain an ozone-dissolved glycerin solidified product.

In addition, since it is also assumed that glycerol is oxidized by dissolving ozone in concentrated glycerol, this time, ¹ H-NMR spectrum and ¹³ C-NMR spectrum of raw material glycerol and ozone-dissolved glycerol solution were measured and compared. did. As a result, there was no difference between the spectrum of the raw material glycerin and the spectrum of the ozone-dissolved glycerin solution, and no glycerin oxide was detected. Therefore, it was found that even when high-concentration ozone was dissolved in concentrated glycerin, glycerin was not oxidized by ozone.

  The natural half-life of gaseous ozone is about 2 hours, but the half-life of ozone in the ozone-dissolved glycerin solution is much longer than that, as will be described later. Therefore, it is presumed that ozone in the ozone-dissolved glycerin solution does not exist in the form of bubbles but is dissolved in glycerin. Immediately after actually producing the ozone-dissolved glycerin solution, a large number of bubbles can be observed with the naked eye, but if left for several hours, these bubbles are not observed.

  The ozone-dissolved glycerin solution can be used as it is depending on the application. However, when used in a lotion or a cosmetic liquid, the high concentration of glycerin has irritation to the skin. % Or less is preferable. For this reason, it is preferable to mix and dilute a suitable diluent with ozone solution glycerol solution.

  As such a diluent, those which are not easily oxidized by ozone are suitable, and water, petrolatum, polyethylene glycol and the like are suitable. When water is used as a diluent, it is preferable to use pure water or ultrapure water. This is because if water is contaminated with impurities, it may be oxidized to ozone to generate oxides (peroxides) that irritate the skin or reduce the efficacy.

  When petrolatum is used, it is preferable to use purified petrolatum that has few impurities and is not easily degraded. This is because, if there is an impurity, it is oxidized to ozone, and an oxide (peroxide) is generated that irritate the skin or reduce the medicinal effect. As such refined petrolatum, Propeto (registered trademark) manufactured by Maruishi Pharmaceutical Co., Ltd., Sun White (registered trademark) manufactured by Nikko Rica Co., Ltd., or the like can be used.

  When polyethylene glycol is used, it is desirable to use macrogol ointment defined by the Japanese Pharmacopoeia. Macrogol ointment is a mixture of liquid macrogol 400 and solid macrogol 4000 in a ratio of approximately 1: 1, but the mixing ratio may be changed as appropriate in order to adjust the viscosity according to the application. A polymer agent may be added to adjust the viscosity. Since macrogol is hygroscopic, it can be made into an ointment with high moisture retention by mixing with glycerin.

  The ozone-dissolved mixed solution obtained by diluting the ozone-dissolved glycerin solution with these diluents preferably has an ozone concentration of 80 ppm or more. If the ozone concentration is 80 ppm or more, the sterilizing ability can be exhibited. Moreover, if ozone concentration is 100 ppm or more, sterilization ability can be exhibited more. Furthermore, if the ozone concentration is 500 ppm or more, a wound healing effect can be obtained, and if the ozone concentration is 1000 ppm or more, an excellent wound healing effect can be exhibited as described later.

  The above ozone-dissolved mixed solution can also be further reduced in the amount of ozone released from the ozone-dissolved mixed solution by refrigerated storage at −5 ° C. or more and 10 ° C. or less or frozen storage at −5 ° C. or less. The ozone concentration can be maintained at a high concentration for a longer period than when stored at room temperature.

  Further, the ozone-dissolved mixed solution can be cooled to be an ozone-dissolved glycerin solidified product, similarly to the ozone-dissolved glycerin solution. When the ozone-dissolved glycerin solidified product is used, ozone is less likely to be released than the liquid state, and the ozone concentration can be maintained at a high concentration for a longer period.

  Concentrated glycerin and ozone were brought into gas-liquid contact to produce an ozone-dissolved glycerin solution. Here, the concentrated glycerin means glycerin having a concentration of 98% or more of Japanese Pharmacopoeia.

  A Teflon (registered trademark) tank having a capacity of 50 L was used as the contact tank. A diffuser tube was installed on the bottom of the tank so that ozone could be supplied into the tank as fine bubbles. As the ozone generator, a silent discharge type ozone generator having an ozone generation capacity of 100 g / h using oxygen having a concentration of 90% or more as a raw material was used.

  Put 22kg of concentrated glycerin into the tank, send 20L of oxygen per minute into the ozone generator, release the gas containing the generated ozone from the diffuser into the tank for 7 days, and the ozone dissolved glycerin solution with a final concentration of 3000ppm ozone concentration Got.

  The obtained ozone-dissolved glycerin solution was stored at room temperature, refrigerated (about 5 ° C.), or frozen (about −20 ° C.), and the half-life of the ozone concentration was measured. The potassium iodide titration method was used for the measurement of the ozone concentration.

  When the obtained ozone-dissolved glycerin solution was stored at room temperature, the ozone concentration was halved in about 6 months. When refrigerated, the ozone concentration halved in about 16 months. When stored frozen for 3 years, the ozone concentration change rate was 98%, showing almost no change. This is probably because the glycerin of the ozone-dissolved glycerin solution was crystallized by freezing or the viscosity of the whole solution was increased, so that ozone was less likely to be released than in the liquid state.

  Ozone-dissolved glycerin solution (hereinafter referred to as ozone gel) produced from concentrated glycerin by the above-described production method, ozone-dissolved mixed solution (hereinafter referred to as ozone ointment) in which macrogol ointment is mixed with this, strong electrolytic acid gel, electrolysis A comparison was made with acidic functional water.

[Experimental material]
16 4-week-old male Wistar rats, ozone ointment (manufactured by VMC), ozone gel (manufactured by VMC), strong electrolytic acid gel (manufactured by MIZ), and electrolytic acid functional water (OXILIZER (registered trademark)) as comparative controls Manufactured by Miura Electronics Co., Ltd.).

  Both ozone ointment and ozone gel were used in which the dissolved concentration of ozone was adjusted to 1000 ppm. Strong electrolytic acid gel is soft type with pH 2.14, oxidation reduction potential 463 mV, effective chlorine concentration 0 ppm, and electrolytic acid functional water is adjusted to pH 2.14, oxidation reduction potential 1157 mV, effective chlorine concentration 37.33 ppm. It was.

〔experimental method〕
After anesthetizing the rat with ethyl ether, the back skin was disinfected with hibiten and shaved. Four wound sites having a diameter of 5 mm and a depth of about 1 mm were prepared using a derma punch (manufactured by Stiefel Laboratorium) at the site. Ozone ointment, ozone gel, strong electrolytic acid gel, and electrolytic acidic functional water were applied to each wound site twice a day (AM 9:00, PM 9:00).

  On the first, third, fifth, and seventh days after preparation of the wound site, the diameter of the wound site of the rat was measured, and then immediately sacrificed and a sample was taken. In addition, the measurement of a diameter was performed in four places per one part, and the average value was made into the measurement result.

  The collected sample was embedded in paraffin and sliced, and then stained with HE to observe the degree of epithelial regeneration and granulation tissue formation. Azan staining was also performed to examine the degree of collagen fiber growth during the wound healing process.

[Results and discussion]
<< Macroscopic observation >>
<One day example>
The reduction rate of the wound site diameter was 98.1% for electrolytic acid functional water, 93.5% for strong electrolytic acid gel, 98.0% for ozone gel, and 94.3% for ozone ointment. There was no difference.

<3 days example>
The reduction rate of the wound site diameter was 82.5% for electrolytic acid functional water, 82.5% for strong electrolytic acid gel, 80.5% for ozone gel, and 86.5% for ozone ointment. There was no difference.

<Example of 5 days>
The reduction rate of the wound site diameter was 70.5% for electrolytic acid functional water, 66.5% for strong electrolytic acid gel, 63.5% for ozone gel, and 63.0% for ozone ointment. There was no difference.

<Example of 7 days>
The reduction rate of the wound site diameter was 57.5% for electrolytic acid functional water, 51.0% for strong electrolytic acid gel, 44.0% for ozone gel, and 41.5% for ozone ointment. Significant differences were observed between electrolytic acidic functional water and ozone ointment, electrolytic acidic functional water and ozone gel, strong electrolytic acidic gel and ozone ointment.

<< Histological observation in HE staining >>
<1 day example, 3 day example>
There were no obvious differences.

<Example of 5 days>
Compared to the 3-day example, in the electrolytic acid functional water, regeneration of the granulation tissue was observed, and the absorption promotion of the fibrin layer was observed. In the strongly electrolyzed acidic gel, granulation tissue accompanied by inflammatory cell infiltration was observed in the subepithelium, and regeneration of basal cells and fiber formation toward the wound center were observed to a slight extent. With ozone gel, granulation tissue formation with inflammatory cell infiltration and epithelial regeneration from the wound margin were observed. In ozone ointment, inflammatory cell infiltration in the granulation tissue was slightly relieved, and relatively good epithelial regeneration was observed.

<Example of 7 days>
In the electrolyzed acidic functional water, the granulation tissue disappeared slightly, and the number of mail cells was reduced. In the strong electrolyzed acidic gel, the inflammatory cell infiltration in the subepithelium was almost abolished, formed with fibrous connective tissue, and the formation of capillaries was observed. In the case of ozone gel and ozone ointment, inflammatory cells in the subepithelium were almost eliminated, fibrous connective tissue rich in capillaries was formed, and epithelial regeneration was also good.

<< Histological findings in Azan staining >>
<1 day example, 3 day example>
There were no obvious differences.

<5 days, 7 days>
It was confirmed that the regeneration degree of the fibrous connective tissue was good in the order of ozone ointment, ozone gel, strong electrolytic acid gel, and electrolytic acidic functional water.

  From the above results, ozone ointment exhibited almost the same treatment course from the macroscopic viewpoint as compared with ozone gel and strong electrolytic acid gel. Regarding the degree of epithelial regeneration, ozone ointment was the best histologically, followed by ozone gel, strong electrolytic acidic gel, and electrolytic acidic functional water. Ozone ointment has the merit that it is easy to apply because there is no irritation to the wound part like strong electrolysis acidic gel and ozone gel, suggesting the possibility that it can be applied as a therapeutic agent to the wound part.

Claims (6)

  An ozone-dissolved glycerin solution, wherein ozone is dissolved in a non-oxidized glycerin solution of 75% or more in an amount of 400 ppm or more.   An ozone-dissolved mixed solution, wherein the ozone-dissolved glycerin solution according to claim 1 is mixed with any one of water, petrolatum, and polyethylene glycol, and ozone is dissolved at 80 ppm or more.   The method for producing an ozone-dissolved glycerin solution according to claim 1, wherein gas containing ozone is brought into gas-liquid contact with 75% or more of the glycerin solution.   A method for producing an ozone-dissolved mixed solution according to claim 2, wherein the ozone-dissolved glycerin solution produced by the production method according to claim 3 is mixed with any one of water, petrolatum, and polyethylene glycol. A method for producing an ozone-dissolved mixed solution characterized by stirring.   A method for preserving an ozone-dissolved glycerin solution, wherein the ozone-dissolved glycerin solution in which ozone is dissolved in a non-oxidized glycerin solution is stored in a refrigerator or frozen.   An ozone-dissolved glycerin solidified product obtained by cooling and solidifying an ozone-dissolved glycerin solution in which ozone is dissolved in a non-oxidized glycerin solution.