JP2011105642A - Ozone nano-bubble water for medical use on digestive tract - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To solve the problems wherein, although there are examples of medical applications of ozone nano-bubble water containing stabilized ozone nano-bubbles, such as its use in periodontal treatment etc., based on its strong sterilizing effect, optimum conditions of the ozone nano-bubble water for individual applications, particularly optimum conditions regarding its salt concentration, are not suggested and, because there is no report on its medical use on the digestive tract, such as its use in treatment of infectious diseases in the digestive tract and sterilization of the digestive tract as a minimally invasive preoperative treatment, ozone nano-bubble water optimized for such applications has not been suggested. <P>SOLUTION: The ozone nano-bubble water for medical use on the digestive tract is ozone nano-bubble water wherein the stabilized ozone nano-bubbles are contained in water with salt concentration of approximately 0.9%. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to water containing stabilized ozone nanobubbles, so-called ozone nanobubble water, and is particularly optimized for treatment of gastrointestinal infectious diseases and gastrointestinal sterilization as a minimally invasive surgical pretreatment. Ozone nano bubble water related.

  In antibacterial therapy for gastrointestinal infectious diseases, the use of a large amount of antibacterial agents over a long period of time may cause the generation of multidrug-resistant bacteria. There was a possibility to make it worse. In addition, multidrug or long-term antibacterial therapy has resulted in an economic burden on patients in terms of medical costs.

  In addition, in the surgical operation of digestive organs, in recent years, with the goal of minimally invasive, transluminal endoscopic surgery (Natural surgery) is a surgical method that removes organs transgastrically without damaging the abdominal wall at all. The Orifice Translumenal Endoscopic Surgery (NOTES) method has been developed, but this NOTES method has made it necessary to complete gastrointestinal sterilization in a short time before surgery.

  Historically, there was an era when gastrointestinal sterilization with antibiotics was carried out as a pre-surgical treatment, but, like antibacterial therapy for the above gastrointestinal tract infections, it induces the growth of resistant bacteria and the bacterial replacement phenomenon It is no longer enforced. In addition, antibacterial agents cannot be expected to be sterilized in a short time before surgery, and there is an urgent need to establish a new efficient preoperative cleaning method for the NOTES method.

  By the way, in recent years, water containing nano-sized bubbles in water, that is, water containing desired gas nano-bubbles has attracted attention, and has been applied to various fields such as medicine, agriculture, aquaculture and aquaculture. Yes.

  For example, Non-Patent Document 1 describes the basics and engineering applications of microbubbles and nanobubbles. Non-Patent Documents 2 to 4 describe application to the medical field using ozone nanobubble sterilization ability, ozone nanobubble cell activation ability, tissue preservation ability, and the like. Non-Patent Document 5 describes the application to agriculture, and Non-Patent Document 6 describes the application of micro- or nano-bubbles to the aquaculture / culture field. In addition, Non-Patent Document 1 describes a measurement method using a dynamic light scattering photometer and a measurement method using an electron spin resonance method (ESR) that measures free radicals caused by nanobubbles as a nanobubble analysis method. .

  Furthermore, the generation mechanism of microbubbles, the mechanism of stabilization as nanobubbles, and the method of conceptual stabilization are described in Non-Patent Document 1 above, and specific examples of methods for producing ozone nanobubble water are described in Patent Documents. 1.

  That is, in the method for producing ozone nanobubbles described in Patent Document 1, ozone is supplied to water mixed with electrolyte ions of minerals as microbubbles having a diameter of 10 to 50 μm, and shock waves and water accompanying water discharge are generated. By applying physical stimuli such as compression, expansion, and vortex generated during the flow of gas, the microbubbles are reduced. At this time, hydrogen ions, hydroxide ions, and electrolyte ions are concentrated at the gas-liquid interface and reduced. By acting as a shell that surrounds the periphery of the bubbles, the reduced microbubbles, that is, ozone nanobubbles are stabilized and exist in water. In the present invention, water containing ozone nanobubbles is referred to as “ozone nanobubble water”.

  As described in Item 3 of Non-Patent Document 2, water containing nanobubbles has various potency and bactericidal effects such as repair and regeneration in addition to the ability to preserve tissues against living bodies. In Non-Patent Document 3, in the application to periodontal treatment using the strong bactericidal effect of water containing ozone nanobubbles (10-30 times bactericidal effect compared with chlorinated bactericides), the periodontal pocket by gargle Improvement and decrease in BOP have been reported. Further, it is known that sterilization with ozone or ozone nanobubble water does not generate resistant bacteria.

Japanese Patent No. 4059506

Takahashi, “Basics and Engineering Applications of Micro Bubbles and Nano Bubbles”, Monthly Material Integration, T.I.C., April 25, 2009, Vol. 22, No. 5, p. 2-19 Kanno, “Application of nanobubbles to the medical field”, Monthly Material Integration, T.I.C., April 25, 2009, Vol. 22, No. 5, p. 30-35 Arakawa, 2 others, “Application of nanobubble water to periodontal treatment”, Monthly Material Integration, T.I.C., April 25, 2009, Vol. 22, No. 5, p. 36-43 Hokushin, “Anti-inflammatory and anti-cell proliferation effects of ozone nanobubbles: effects on vascular endothelium and smooth muscle cells”, Monthly Material Integration, T.I.C., April 25, 2009, Volume 22, Volume 5 No., p. 44-48 Tamaki, “Possibility of using microbubbles in the agricultural field-Sterilization of hydroponic culture using ozone microbubbles”, Monthly Material Integration, T.I.C., April 25, 2009, No. Vol. 22, No. 5, p. 20-23 Yamamoto, “Application of microbubbles to aquaculture and aquaculture”, Monthly Material Integration, T.I.C., April 25, 2009, Vol. 22, No. 5, p. 24-29

  As shown in the above-mentioned literature, there are conventional examples of applying to the medical field such as periodontal treatment using the powerful bactericidal effect of ozone nanobubble water, but ozone nanobubble water is used for each application. However, no optimized ozone nanobubble water conditions, in particular, optimum conditions for the salinity thereof have been proposed.

  For example, in the past, for example, Non-patent Document 3, page 40, left column, lines 4 to 8, “4 patients with moderate periodontitis, subject to ozone nanobubble water stock solution once, 20 ml, 20 seconds As a result, 61.8% of the periodontal pockets of 3 mm or more (139 out of 225 sites improved by 1 mm or more) was used for industrial use. In addition, ozone nanobubble water available for fishery processing is used as it is, and the point of optimizing the salt concentration is not disclosed. In addition, the salinity of ozone nanobubble water which can be obtained in this way was about 2%.

  In addition, there are still reports of examples used for medical treatment of the digestive tract, such as ozone nanobubble water, treatment of infectious diseases of the digestive tract as described above, and digestive tract sterilization as a minimally invasive surgical pretreatment Therefore, ozone nanobubble water optimized for these applications has not been proposed yet.

  Therefore, an object of the present invention is to provide ozone nanobubble water optimized for medical use for the digestive tract.

  In order to solve the above problems, the present invention proposes medical ozone nanobubble water for the digestive tract containing stabilized ozone nanobubbles in water having a salt concentration of 0.9% or a value in the vicinity thereof.

  In the present invention, the ozone nanobubble water described above is proposed to be used for sterilization of the digestive tract, removal of the mucosal epithelium layer of the digestive tract, or induction of intraepithelial lymphocytes.

  In light of the above-described current state of medical treatment for the digestive tract, the present inventor has focused on ozone nanobubble water having many features, and as a result of diligent research and experiments, has come up with ozone nanobubble water optimal for medical treatment of the digestive tract. It came to do.

  That is, first, the bactericidal effect of ozone nanobubble water was tested by changing its salt concentration. As a result, it was found that the bactericidal effect was dependent on the salinity concentration regardless of the aerobic and anaerobic species, and the salinity peaked at 0.9%. Conventionally, it was found that ozone nanobubble water having a salinity concentration of about 2% used for sterilization in the industrial field and fishery processing field has a remarkably small sterilization effect.

  Therefore, aerobic bacteria such as Helicobacter pylori can be obtained by using ozone nanobubble water with a salinity of 0.9% or a salinity in the vicinity of the digestive tract, such as the stomach, small intestine, and large intestine. Bacteria and anaerobic bacteria can be eradicated without causing the problem of resistant bacteria.

  Next, the action of ozone nanobubble water on the gastrointestinal mucosa was examined by changing its salt concentration. As a result, it was found that the ozone nanobubble water has a salinity-dependent effect on the removal of the mucosal epithelium, which can be regarded as mucosal damage, as well as the above-mentioned bactericidal effect, and is the highest at a salt concentration of 0.9%. When the state of the mucous membrane at this time is observed in detail, in normal ozone water, the corrosive action occurs across the entire mucosa and an ulcer is formed, whereas in ozone nanobubble water, only one layer of the mucosal epithelium is formed. It has been found that it has a specific mucosal removal effect that is removed.

  Therefore, when ozone nanobubble water with a salinity of 0.9% or near it is used for viral inflammation of the gastrointestinal mucosa, for example, viral gastroenteritis, this inflammation only affects the mucosal epithelium. Since it is a pathological condition that infects, destroys, and develops its clinical symptoms, the infected mucosal epithelium can be removed early with ozone nanobubble water, contributing to healthy mucosal regeneration.

  On the other hand, as a result of investigating the action on the gastrointestinal mucosa by ozone nanobubble water having a salinity of 0.9% or in the vicinity thereof, the mucosal epithelium includes not only the layer to be removed but also the epithelium famous for its antitumor effect Induction of internal lymphocytes was confirmed.

  The phenomenon of induction of intraepithelial lymphocytes means enhancement of local immunity of the mucous membrane. Therefore, by using ozone nanobubble water in the gastrointestinal mucosa, a delayed bactericidal effect against bacteria can be provided.

FIG. 1 is a photomicrograph of colonic mucosa washed with 0.9% ozone nanobubble water of the present invention. FIG. 2 is an enlarged photomicrograph of the colonic mucosa washed with 0.9% ozone nanobubble water of the present invention. FIG. 3 is a photomicrograph of colonic mucosa washed with 0.1% ozone nanobubble water with a salt concentration. FIG. 4 is a photomicrograph of colonic mucosa washed with physiological saline.

Next, the form for implementing this invention is demonstrated.
The ozone nanobubble water of the present invention is supplied by supplying ozone gas as microbubbles having a size of 50 μm or less to a raw material water having a salt concentration of 0.9% or higher using, for example, a production method as shown in Patent Document 1 described above. In the mixed state, a physical stimulus is applied and generated.

  That is, ozone supplied as microbubbles with a size of 50 μm or less is shrunk and reduced by physical stimulation. At this time, hydrogen ions, hydroxide ions, and electrolyte ions in the water are concentrated at the gas-liquid interface and reduced. By acting as a shell surrounding the periphery of the formed microbubbles, the microbubbles are stabilized and exist in the water, and thus ozone nanobubble water containing the stabilized ozone nanobubbles is generated. .

  The salinity of ozone nanobubble water is adjusted to 0.9% or a value in the vicinity thereof before or after the above-described crushing step. For example, seawater well water with a salinity of about 2% or clean seawater with a salinity of about 3% is used as the raw water. In this case, these raw waters are crushed and permeated through a reverse osmosis membrane. By using the demineralized water as dilution water, the salt concentration can be adjusted to a predetermined value.

<Test for confirming various effects of ozone nanobubble water according to the present invention>
In order to confirm the above-described various effects of the ozone nanobubble water according to the present invention, a colon washing test using pigs as shown below was performed.
1. Test model creation • A model was developed to evaluate the degree of colon cleansing by the transanal of pigs.
・ The types of pigs were unified to domestic pigs, and were almost unified to 40 kg and BMI: 20.
・ Pigs that were the subject of model creation did not perform any intestinal preparation (laxative administration / fasting) prior to model creation.
・ Pig feed (BREED 72: Corn 61%, Oil cake 22%, Rice bran 9%, Fish)
meal1%, Calcium carbonate 0.8%, Calcium phosphate 0.55%: Japan Agriculture East Papan Kumiai Shiryo
co.).
-Model creation was performed by general anesthesia with GOF (Foren: registered trademark).
2. Cleaning method Colon cleaning uses a normal endoscope for cleaning and a laparoscopic pressurized cleaning system for high-speed cleaning of the digestive tract (Bird's “Hydroflex: registered trademark”). After attaching the lower washing nozzle, ligate the 1.5cm part of the intestinal tract with 4mm wide ligation bands and fix it at high speed so that there is no leakage.
3. Specimen preparation method Bacteria specimens, formalin tissue specimens and frozen section specimens are prepared by excising the same part in the minor axis direction by φ5 mm from the large intestine to be cleaned.
4). Specimen test method ・ Bacteria specimens were homogenized under anaerobic conditions so that they would not be heated with an ultrasonic homogenizer, then distributed to aerobic and anaerobic cellporters, and each cell culture was performed. Later, the type and number of bacteria were calculated.
-Formalin tissue specimens were sliced to 4 μm, stained with hematoxylin and eosin, and histologically determined.
-Freezing sections were identified for dendritic cells and cytotoxic T lymphocytes by immunostaining for CD56 and CD14.

[Test 1]
Make a small incision 10cm in diameter on the left abdomen of the pig, release the spiral colon from the upper rectum to the transverse colon and further to the mouth 30cm, take a total length of 120cm, cut it 15cm apart, 8 conditions A model was created so that an experiment of sterilization by washing could be performed. And in those models, in addition to the ozone nanobubble water according to the present invention, as the cleaning liquid, 0.10%, 0.25% and 0.75%, which are lower in salinity than the present invention, and higher in salinity, conventionally, industrial fields and fisheries Preservative washing is performed using 2.0% ozone nanobubble water used for sterilization in the processing field and physiological saline as a control, and the mucous membrane is anaerobic so that the bacterial specimen is not heated by an ultrasonic homogenizer. The cells were homogenized under the conditions, then allocated to an aerobic culture cellporter and an anaerobic culture cellporter. After cell culture in each, the type and number of bacteria were calculated. The results are shown in Table 1.

  As shown in Table 1, the bactericidal effect of ozone nanobubble water is dependent on its salt concentration regardless of the aerobic and anaerobic species, and the bactericidal effect is maximum at 0.9%. It can be seen that the sterilizing effect decreases even if it is higher or lower than that. For example, at 0.1%, the bactericidal effect is very low, the remaining bacteria are almost the same as physiological saline, and the salt concentration, which has been conventionally used for sterilization in the industrial field and fishery processing field, is about Although 2% ozone nanobubble water shows a bactericidal effect compared with physiological saline and 0.1%, the bactericidal effect is similar to the concentration of 0.25% and 0.75%, compared with 0.9% according to the present invention. It turns out that it is very low.

[Test 2]
A test similar to test 1 was performed on pigs different from test 1. In this case, in addition to the ozone nanobubble water according to the present invention, ozone nanobubble water having a salt concentration of 0.10% and 2.0% and physiological saline as a control were used as the cleaning liquid. As in Test 1, Table 2 shows the results of calculating the types and number of bacteria after cell culture.

  Table 2 also shows that the bactericidal effect of ozone nanobubble water is dependent on its salt concentration regardless of the aerobic and anaerobic species, and the bactericidal effect is maximum at a salt concentration of 0.9%. I understand.

[Test 3]
Make a small incision of 10cm in the left abdomen of the pig, release the helix from the anal edge to the transverse colon and 30cm from the joint of the spiral colon of the transverse colon to the mouth side, and wash with the above washing method It was. In this case, as cleaning water, the ozone nanobubble water according to the present invention, which had the highest bactericidal effect in Test 1 and Test 2, was performed.

  After washing, the colon to be washed is excised over the entire length, separated into two parts, 10cm from the anus and 30cm from the anus, and the intestinal tract in the long axis direction. An incision was made instantaneously, and a total of three mucous membranes were immediately excised and φ5 mm excised from the same part in the short axis direction, and a bacterial specimen, a formalin tissue specimen and a frozen section specimen were prepared as described above.

  Table 3 shows the change in the number of bacteria when the colon was washed with ozone nanobubble water according to the present invention for the bacterial specimen at a site 30 cm away from the anus and the bacterial specimen in the upper rectum 10 cm from the anus. The change in the number of bacteria is shown. In the figure, 1 L indicates a case where 1 liter is washed, and 2 L indicates a case where 2 liters are washed.

  The test results shown in Table 3 show the difference in the bactericidal effect depending on the anatomical part of the digestive tract in washing with ozone nanobubble water according to the present invention. That is, as shown in Table 3, it can be seen that by washing the large intestine with the ozone nanobubble water according to the present invention, a good bactericidal effect regardless of aerobic / anaerobic can be obtained.

  On the other hand, when the lavage was performed from the mouth side of the large intestine to the anal side as in this test, the test results show that the bactericidal effect in the rectum, particularly the upper rectum, is small compared to other sites. It turned out from. This phenomenon is presumed to be derived from the structural characteristics of the large intestine, and when sterilization in the large intestine is considered, it has been found that it is essential to confirm the sterilization effect in the rectum.

  Therefore, the present inventor confirmed the eddy current in the digestive tract by placing an endoscope in the rectum while performing continuous washing from the mouth side with ozone nanobubble water and flowing a small amount of methylene blue. Then, in the upper rectum, ozone nanobubble water stagnates on the mucosal surface due to the backflow from the lower part, and one of the reasons why the bactericidal effect in the upper rectum deteriorates is the mucosal crypt of ozone nanobubble water. It was found that this was because the approach was blocked.

  From the above, when applying ozone nanobubble water to digestive tract sterilization, it is necessary to determine the cleaning conditions (cleaning time and amount) in consideration of the anatomical structure of the digestive tract and the mucosal structure. And gained knowledge.

[Test 4]
As in test 3, a small incision with a major axis of 10 cm was made in the left flank of the pig, the spiral was released from the anal edge to the transverse colon, and 30 cm from the junction of the spiral colon of the transverse colon to the mouth side, and the washing described above Washing was performed by the method. In this case, as washing water, in addition to the ozone nanobubble water according to the present invention, 2.0% ozone nanobubble water having a higher salt concentration than the present invention and physiological saline as a control were used. Furthermore, the effect of using a conventional liquid laxative such as NIFREC (registered trademark) in the washing water was tested. In the same manner as in the above-described test, the bacterial specimen was homogenized and then cell culture was performed to calculate the type and number of bacteria. The results are shown in Tables 4 and 5. Table 4 shows the test results for a bacterial specimen at a site 30 cm from the anus, and Table 5 shows the test results for a bacterial specimen at a site 10 cm from the anus.

  From the test results of Tables 4 and 5, it can be seen that in cleaning the large intestine, the ozone nanobubble water according to the present invention has a much higher bactericidal effect than the ozone nanobubble water having a salt concentration of 2.0%, and as described above, When washing from the mouth side toward the anal side, the bactericidal effect in the rectum, particularly the upper rectum, is small compared to other parts, in addition to the ozone nanobubble water according to the present invention, It was found that the bactericidal effect is higher when a liquid laxative such as NIFREC (registered trademark) is used together.

[Test 5]
The formalin tissue specimen obtained in Test 3 was sliced into 4 μm and the mucosa stained with hematoxylin eosin was observed histologically.
As described above, FIG. 1 is a photomicrograph of colonic mucosa washed with ozone nanobubble water according to the present invention, and FIG. 2 is an enlarged photo. FIG. 3 is a photomicrograph of the colonic mucosa washed with 0.1% ozone nanobubble water, and FIG. 4 is a photomicrograph of the colonic mucosa washed with physiological saline.

  First, as shown in FIG. 3 and FIG. 4, no abnormality was observed in the cells of the colonic mucosa washed with 0.1% ozone nanobubble water or physiological saline, and mucin quality on the mucous membrane was also retained. Yes.

  In contrast, in the colonic mucosa washed with ozone nanobubble water with a salt concentration of 0.9%, as shown in FIGS. 1 and 2, only one surface epithelial cell is missing as if it was scraped off with a blade. In addition, disappearance of mucus in mucosal crypts (invagination) is observed.

  The so-called ozone water in which ozone is simply dissolved in water is used for sterilization, and when the mucous membrane is washed with this ozone water, the corrosive action is spread over the entire mucous membrane, While it is known that ulcers are formed, the ozone nanobubble water according to the present invention has a specific mucosal removal effect that only one layer of mucosal epithelium is removed. These findings were obtained from FIG. 1 and FIG.

  Considering the use of such a specific mucosal removal effect, for example, viral inflammation of the gastrointestinal mucosa, such as viral gastroenteritis, is a pathological condition that infects only the mucosal epithelium and destroys it to manifest its clinical symptoms Therefore, the use of ozone nanobubble water according to the present invention may contribute to healthy mucosal regeneration by removing only the infected mucosal epithelium when used for such diseases.

  On the other hand, as described above, in the mucous membrane of the colon washed with ozone nanobubble water with a salt concentration of 0.9%, in addition to the lack of only one layer of mucosal epithelium, mucus of mucosal crypt (invagination) has also disappeared. It is considered that the nanobubble water reaches the inside of the mucosal crypt and exerts a bactericidal effect, which is interpreted as the reason why the bacteria are not detected even in the culture after homogenizing the bacterial specimen.

  Therefore, if the ozone nanobubble water according to the present invention is used for sterilization by washing the digestive tract before surgery, bacteria will not grow on the cells even after the surgery time has passed after washing, and it is possible to cope with surgery for a long time Showing sex.

In addition to the above, in the colonic mucosa washed with ozone nanobubble water having a salt concentration of 0.9%, many lymphocytes are observed in the mucosal epithelium as shown in FIGS. These lymphocytes are Intra Epithrial Lymphocytes that are famous for their anti-tumor effects, and a phenomenon of induction in the mucosa is observed.

  Such induction phenomenon of intraepithelial lymphocytes means enhancement of local immunity of the mucous membrane. Therefore, by using the ozone nanobubble water according to the present invention for the gastrointestinal mucosa, a delayed bactericidal effect on bacteria. The possibility of providing

  As described above, when the stomach is cleaned using the ozone nanobubble water according to the present invention having a high bactericidal effect, the ozone nanobubble water is washed after the gastric juice so that the bactericidal effect of the ozone nanobubble water is not diminished by the stomach acid. It is good to administer.

  Gastric lavage can be performed by administering a normal amount of aluminum hydroxide, a gastric ulcer treatment drug, which is certified by insurance, followed by effective sterilization of the stomach by administering ozone nanobubble water. It can be carried out. In addition, about 300 ml of distilled water (no problem if tap water containing no ions) is orally ingested 30 minutes after the administration of aluminum hydroxide, and then after 10 minutes, for example, ozone nanobubble water is administered. Is more effective. Since this timing differs markedly depending on the degree of gastric mucosal atrophy and the pH in the stomach, it is more effective to administer ozone nanobubble water after using aluminum hydroxide and measuring pH to confirm neutralization. It is.

Since the ozone nanobubble water which concerns on this invention is as above, it can be used with respect to each part of a digestive tract, and the following special effects and effects can be obtained.
(Large intestine)
1: Wide bactericidal effect regardless of aerobic / anaerobic 2: Removal effect of mucosal epithelial layer (removal of infectious mucosa and normal mucosal regeneration)
3: Induction of intraepithelial lymphocytes (bactericidal effect by delayed immune cells)
(Stomach)
1: Wide bactericidal effect regardless of aerobic / anaerobic 2: Removal effect of mucosal epithelial layer (removal of infectious mucosa and normal mucosal regeneration)

In use, it is effective to pay attention to the following points.
(Large intestine)
1: Since the bactericidal effect of the upper rectum is the weakest, the washing conditions (washing time and amount) are made larger at this site.
(Stomach)
1: Administration of drinking water, neutralization of gastric acid with aluminum hydroxide and administration after drinking water is effective for eradication of Helicobacter pylori in order to prevent the effects of gastric acid from being reduced.

Claims (4)

Medical ozone nanobubble water for the digestive tract characterized by containing stabilized ozone nanobubbles in water having a salt concentration of 0.9% or in the vicinity thereof. The medical ozone nanobubble water for the digestive tract according to claim 1, which is used for sterilization of the digestive tract. The medical ozone nanobubble water for the gastrointestinal tract according to claim 1, which is used for removing a single layer of mucosal epithelium of the gastrointestinal tract. The medical nanobubble water for the gastrointestinal tract according to claim 1, which is used for induction of intraepithelial lymphocytes.