Microbubble dispersion

JP7637707B2Active Publication Date: 2025-02-28大平 勐
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Patent Information

Application Number
JP2023000326
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Filing Date
2023-01-04
Publication Date
2025-02-28
Estimated Expiration
2037-12-08

AI Technical Summary

Benefits of technology

【0014】 本発明によれば、ナノバブルを含むナノバブル分散液又は/及びマイクロバブルを含むマイクロバブル分散液を医療分野に有効に利用することができる。

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Abstract

Nanobubble dispersions or microbubble dispersions are effectively used in medical treatment. The antibacterial effect on pathogenic microorganisms is controlled by contacting a nanobubble dispersion containing positively or negatively charged nanobubbles with an average particle size of 10 to 500 nm with the pathogenic microorganisms.
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Description

[Technical field]

[0001] The present invention relates to a dispersion of microbubbles, and more particularly to a dispersion of microbubbles containing nanobubbles and / or microbubbles for medical use. [Background technology]

[0002] Nanobubble dispersions contain minute bubbles with a diameter of less than 1 μm and have the effect of promoting the physiological activity of living organisms, and therefore have attracted attention in various industrial fields. As prior art, Patent Documents 1 and 2 describe methods for producing nanobubble dispersions.

[0003] However, these prior art documents do not disclose the use of nanobubble dispersions in the medical field, and although microbubbles, which have a larger particle size than nanobubbles, are thought to have similar effects to nanobubbles, they do not disclose the use of microbubble dispersions in the medical field. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2009-131768 A [Patent Document 2] Patent No. 4144669 Summary of the Invention [Problem to be solved by the invention]

[0005] In view of the above, an object of the present invention is to provide a means for enabling effective use of nanobubble dispersions or microbubble dispersions in the medical field. [Means for solving the problem]

[0006] The present invention is characterized in that a nanobubble dispersion containing positively or negatively charged nanobubbles with an average particle size of 10 to 500 nm is brought into contact with an affected area.

[0007] It is preferable that the nanobubble dispersion liquid be brought into contact with an affected area to control the antibacterial effect against pathogenic microorganisms in the affected area.

[0008] It is also preferable that the nanobubble dispersion liquid is brought into contact with the affected area to disrupt tumor cells in the affected area.

[0009] The present invention is characterized in that a microbubble dispersion liquid containing positively or negatively charged microbubbles with an average particle size of 1 to 900 μm is brought into contact with an affected area.

[0010] It is preferable that the microbubble dispersion liquid is brought into contact with the affected area, whereby the ballooning effect of the microbubbles is utilized to break up and wash away bloody or non-bloody infectious viscous discharge or bloody or non-bloody infectious exudate from the affected area.

[0011] It is preferable that the microbubble dispersion liquid is brought into contact with the affected area, whereby the blood clots in the affected area are disrupted and removed by the ballooning effect of the microbubbles.

[0012] It is preferable that the microbubble dispersion liquid is brought into contact with the affected area, whereby tumor cells in the affected area are detached and removed by the ballooning effect of the microbubbles.

[0013] The method is characterized in that a mixture of a nanobubble dispersion containing positively or negatively charged nanobubbles with an average particle size of 10 to 500 nm and a microbubble dispersion containing positively or negatively charged microbubbles with an average particle size of 1 to 900 μm is brought into contact with the affected area. Effect of the Invention

[0014] According to the present invention, a nanobubble dispersion containing nanobubbles and / or a microbubble dispersion containing microbubbles can be effectively used in the medical field. [Brief description of the drawings]

[0015] [Figure 1] FIG. 1 is a schematic diagram illustrating the effect of microbubbles on viscous exudates or infectious exudates. [Diagram 2] FIG. 13 is a diagram showing a comparison of the time required for detachment of cancer cells with a control, showing the serosal detachment property of the cancer cells. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] The present invention will be specifically described below with reference to each embodiment. In the present invention, a nanobubble dispersion, a microbubble dispersion, or a mixture of these dispersions is brought into contact with the affected area.

[0017] The nanobubble dispersion liquid used in the present invention is formed by dispersing nanobubbles in a liquid. As the nanobubbles, nano-order microbubbles with an average particle size of 10 to 500 nm are used. Bubbles with an average particle size of less than 10 nm are undesirable because the bubbles are too small and have a reduced effect on tissues for medical purposes, while those with an average particle size of more than 500 nm are undesirable because the dispersibility in the liquid decreases, resulting in a reduced effect on tissues for medical purposes.

[0018] The nanobubbles are dispersed in the liquid in a positively or negatively charged state. By being positively or negatively charged, the nanobubbles repel each other, improving their dispersibility in the liquid. The improved dispersibility allows the nanobubbles to come into contact with the affected area evenly. The nanobubbles can be contacted with the affected area by applying the dispersion liquid to the affected area, placing gauze soaked in the dispersion liquid on the affected area, immersing the affected area in the dispersion liquid, or the like.

[0019] Nanobubbles are 10 per cc of liquid. 5 ~10 10 It is preferable that the nanobubbles contain about 10 to 200 mV. This content allows the nanobubbles to exert a good effect on tissues. Furthermore, it is preferable that the nanobubbles have a zeta potential of 10 to 200 mV. If the zeta potential is outside this range, the dispersibility in the liquid decreases, which is not preferable. The liquid to disperse the nanobubbles in is selected from ozonated water and sterilized water. Of these, ozonated water can use ozone as the nanobubbles.

[0020] In the present invention, the nanobubble dispersion liquid is brought into contact with the tissue of the affected area. In the case of pathogenic microorganisms, the nanobubble dispersion liquid is brought into contact with the tissue of the affected area to kill the pathogenic microorganisms, thereby improving the antibacterial effect. This is because the charged nanobubbles electrostatically bind to the cell membrane of pathogenic microorganisms, puncture and destroy the cell membrane, and intracellular structures such as the nucleus escape, resulting in the death of the cell. If ozone is contained in the solution, the cell membrane is also destroyed by the ozone. When the charged nanobubbles come into contact with the affected cells, they enter the cells by endocytosis or phagocytosis, are transported to the lysosomes in the cells, destroying the lysosomes, and the protoplasm of digestive enzymes in the lysosomes is lost, destroying the cells from the inside.

[0021] In the present invention, tumor cells such as cancer cells can be disrupted and killed by contacting the nanobubble dispersion with the tumor cells. As with pathogenic microorganisms, when nanobubbles come into contact with tumor cells such as cancer cells, the charged nanobubbles electrostatically bond to the tumor cells, puncture them, destroy the cell membrane, and cause the intracellular structures such as the cell nucleus to escape, resulting in the death of the cells. If ozone is included, the destruction of the cell membrane is also caused by the ozone. This results in the antitumor effect. In addition, when charged nanobubbles come into contact with cells, they enter tumor cells by endocytosis or phagocytosis, are transported to the lysosomes in the tumor cells, and destroy the lysosomes, causing the protoplasm of digestive enzymes in the lysosomes to be lost, destroying the tumor cells from the inside. This also exerts antitumor properties.

[0022] In the present invention, a microbubble dispersion can be used in addition to a nanobubble dispersion. A microbubble dispersion is formed by dispersing microbubbles of micron order with an average particle size of 1 to 900 μm in a liquid. If the average particle size is less than 1 μm, the action force on the tissue for medical purposes is undesirably small, and if the average particle size exceeds 900 nm, the dispersibility in the liquid decreases, resulting in a decrease in the action force on the tissue for medical purposes, which is undesirable.

[0023] Microbubbles are dispersed in a liquid in a positively or negatively charged state. By being positively or negatively charged, the microbubbles repel each other, improving the dispersibility in the liquid. And the good dispersibility allows the microbubbles to contact the tissue evenly. In addition to the above, microbubbles, like nanobubbles, have a density of 10 5 ~10 10 It is preferable that the content of microbubbles is about 10 to 200 mV. By setting the content at this level, the action force on tissue can be exerted well. Furthermore, it is preferable that the microbubbles have a zeta potential of 10 to 200 mV. If the zeta potential is outside this range, the dispersibility in the liquid decreases, which is not preferable.

[0024] When the affected area is a bloody or non-bloody infectious viscous discharge or a bloody or non-bloody infectious exudate, the microbubble dispersion of the present invention is brought into contact with the bloody or non-bloody infectious viscous discharge or bloody or non-bloody infectious exudate at the affected area. Microbubble dispersions have a ballooning effect. The ballooning effect is a phenomenon in which microbubbles expand to a size of several mm within a few seconds to several tens of seconds. When the microbubble dispersion comes into contact with bloody or non-bloody infectious viscous discharge or bloody or non-bloody infectious exudate, the ballooning effect causes the microbubble dispersion to be broken down into sizes ranging from several μm to several hundred μm, thereby significantly improving the cleaning efficiency. More specifically, the microbubbles have a contractile Coulomb force due to being electrically charged, and the microbubble dispersion liquid controls the tendency of the bubbles to increase in size by balancing with the entropy increasing force of the gas molecules inside the bubbles, thereby breaking up the viscous exudates and viscous exudates with the ballooning effect brought about by the microbubbles, thereby significantly improving the cleaning efficiency.

[0025] Figure 1 is a schematic diagram explaining the action of microbubbles in this case. Taking advantage of the electrostatic charge and small size of microbubbles, they penetrate into viscous secretions such as sputum, and the ballooning effect of the microbubbles breaks up the viscous secretions from the inside. At this time, the viscous secretions are broken down leaving only the fiber fibers, so that the viscous secretions can be quickly and completely washed. This makes it possible to complete debridement (removal and washing of bad granulation tissue and necrotic tissue) in a short time, and instantly and completely remove local contaminating factors that delay wound healing at the naked eye level.

[0026] When the affected area is a blood clot, the microbubble dispersion of the present invention can be brought into contact with the blood clot, and the blood clot can be broken up and removed by the ballooning effect of the microbubbles. This action is the same as that shown in FIG. 1 above.

[0027] Taking advantage of the electrostatic charge and small size of microbubbles, the microbubbles penetrate into the clot, and the ballooning effect of the microbubbles breaks the clot from the inside, leaving only the fiber fibers. This allows the clot to be washed quickly and completely, and therefore the field of view during surgery can be secured by washing the clot.

[0028] Generally, bleeding from the spleen causes a huge intraperitoneal hematoma and bloody ascites. Conventionally, no matter how long the irrigation nozzle is washed with saline, a jelly-like blood clot remains and clogs the irrigation nozzle. However, in the present invention, even after the intraperitoneal hematoma and bloody ascites are filled by bleeding from the spleen, the mist of saline may become cloudy for 5 seconds due to the ballooning effect, but after that, all the blood clots can be crushed. This allows the intraperitoneal irrigation to be performed while maintaining a clear field of vision, and allows for early return and continuation of the surgical procedure.

[0029] When the affected area is tumor cells such as cancer cells, the microbubble dispersion of the present invention is brought into contact with the tumor cells, and the tumor cells are detached and removed by the ballooning effect of the microbubbles. Explained below taking cancer cells as an example.

[0030] Cancer cells adhere to serosal membranes such as the peritoneum, pleura, and pericardium through extracellular adhesion factors, and cancer serosal dissemination metastasis is established in the serosal membrane. In contrast, when a microbubble dispersion is brought into contact with cancer cells, the charged microbubbles are interposed between the cancer cells and the serosal membrane due to their electrical junction and their invasiveness due to their small size. The ballooning effect of the charged microbubbles lifts the cancer cells between the cancer cells and the serosal membrane in the same manner as a car jack. This causes the cancer cells to detach from the adhesion between the cancer cells and the serosal membrane due to the cancer cell adhesion factors, and it is possible to prevent and remove serosal dissemination metastasis.

[0031] Figure 2 shows a comparison of the time required for detachment with the control, which shows the serosal detachment of cancer cells. The superiority of the electrocharged microbubble dispersion in detachment and washing is shown for all cancer cells. Figure 2 shows cancer cells that are the subject of surgical procedures, with "AGS" being gastric adenocarcinoma, "KATO III" being gastric cancer, "ASPC-1" being metastatic pancreatic cancer, "MIAPaCa-2" being pancreatic cancer, "HepG2" being liver cancer, "DlD-1", "HT-29" and "LS180" being colon adenocarcinoma.

[0032] In the present invention, the above-mentioned nanobubble dispersion and microbubble dispersion are mixed and used for treatment by contacting the affected area. When the mixed liquid is used, the effects of both the nanobubble dispersion and the microbubble dispersion can be exhibited. That is, the nanobubble dispersion can provide antibacterial properties against pathogenic microorganisms and crush tumor cells, and the microbubble dispersion can crush and wash bloody or non-bloody infectious viscous discharge or bloody or non-bloody infectious exudate due to the ballooning effect of the microbubbles in the dispersion, crush and remove blood clots, and exfoliate and remove tumor cells.

Claims

1. A dispersion for removing cancer cells and serosal membrane adhesion, comprising: containing electrically charged microbubbles having an average particle size of 1 to 900 μm; The charged microbubbles are 10 5 ~10 10 Includes 1 piece A dispersion for detaching cancer cell / serosa adhesion, characterized in that the charged microbubbles lift the cancer cells between the cancer cells and the serous membrane due to a ballooning effect of the charged microbubbles, thereby detaching and removing the cancer cells from the serous membrane.

2. The cancer cells are cancer cells that establish serosal dissemination metastasis by adhering to a serosal membrane, The dispersion for detaching cancer cells / serosa adhesion described in claim 1, characterized in that the dispersion for detaching cancer cells / serosa adhesion is intended to prevent serosal dissemination metastasis by detaching and removing the cancer cells from the serosal membrane.

Citation Information

Patent Citations

  • Production method of nano-bubble

    JP2005245817A

  • Water purifying and softening device

    JP2009131768A

  • Method for manufacturing nanobubbles

    JP4144669B2