WO2012086635A1 - 心筋梗塞を予防、改善又は治療するための炭酸ガスミスト圧浴方法及び炭酸ガスミスト圧浴装置 - Google Patents
心筋梗塞を予防、改善又は治療するための炭酸ガスミスト圧浴方法及び炭酸ガスミスト圧浴装置 Download PDFInfo
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Definitions
- carbon dioxide carbon dioxide: CO 2
- water-soluble water-soluble
- oil lipid-soluble
- carbon dioxide has traditionally improved the properties of water and oil. It is known that when touching the skin and mucous membrane of a living body, it penetrates into the skin of the living body and expands the blood vessels at the site of penetration to improve blood circulation.
- Blood containing a large amount of carbon dioxide gas is recognized as a so-called “oxygen deficiency” state, and blood vessels are dilated to promote blood flow increase. ). In tissues, it is thought that CO 2 is used to promote metabolism and support angiogenesis.
- the inventor of the present application makes the carbon dioxide gas in a mist form (mist form) in order to efficiently incorporate the carbon dioxide gas into the blood. That is, carbon dioxide gas is confined in a thin film bubble (in this application, this is called “carbon dioxide mist”), and a predetermined pressure (above the internal pressure of the living body) is applied to the skin and mucous membrane of the living body. It was discovered that the contact increases the concentration of carbon dioxide gas taken into the blood, improves the ischemic region in the myocardial infarction disease part, and dilates the myocardial blood vessel to improve the infarct state of the blood vessel.
- carbon dioxide mist a thin film bubble
- a predetermined pressure above the internal pressure of the living body
- the carbon dioxide mist contains carbon dioxide mist having a particle size of 10 ⁇ m or less. Further, the atmospheric pressure in the carbon dioxide mist surrounding means in the step (c) is 1.01 to 2.5 atm. And the density
- the amount of carbon dioxide mist supplied from the carbon dioxide mist generating and supplying means is adjusted so that the atmospheric pressure is within a predetermined range.
- Gosuru control means there is provided a carbon dioxide mist pressure bath device characterized by comprising the means of the.
- NO 3 ⁇ blood nitrate ions
- NO 3 ⁇ is a relatively stable oxidative metabolite derived from NO (nitrogen monoxide), which is the main body of the endothelial cell-derived relaxation factor EDRF in blood, and NO is released from vascular endothelial cells.
- NO nitrogen monoxide
- vascular endothelial function is involved in the blood flow improving effect or cardiac remodeling suppressing effect of high concentration (80 to 100%) carbon dioxide mist treatment.
- test results of various animal experiments relating to the improvement of myocardial infarction disease described in the present specification are mainly for 8-week-old Wistar rats, but this is applicable to the human body and other mammalian organisms. It is clear from the correlation between many other experimental examples of the species and clinical data.
- Serum nitrate ion (NO 3 -) is a diagram showing the average value of each population when measuring. It is a figure which shows the average value of each individual group when the blood vessel endothelial growth factor (VEGF) in serum is measured. It is a figure which shows the average value of each population when measuring the vascular endothelial growth factor (VEGF) in a myocardium. It is a figure which shows the average value of each individual population when the size of myocardial infarction is measured. It is a figure which shows the average value of each individual group when a heart rate is measured.
- VEGF blood vessel endothelial growth factor
- FIG. 1 shows a process flow of a carbon dioxide mist pressure bath method for preventing, improving or treating myocardial infarction of a living body according to the present invention.
- a carbon dioxide mist generating / supplying device which will be described in detail later (in FIGS. 2 and 5)
- carbon dioxide mist is obtained by pulverizing and dissolving carbon dioxide into a liquid and atomizing it.
- step (e) the supply amount of the carbon dioxide mist is controlled and continued for at least 20 minutes. Preferably, it is continued for 30 minutes or more to prevent, improve or treat myocardial infarction in the living body. Best on.
- the carbon dioxide mist generating means 113 is an apparatus that generates carbon dioxide mist obtained by crushing and dissolving the gas supplied from the carbon dioxide supply means 111 and the liquid supplied from the liquid supply means 112 and supplying the carbon dioxide mist to the pressure bath cover 12. is there. At this time, the particle size of the mist to be generated is optimally 10 ⁇ m or less.
- various mist generating apparatuses such as an ultrasonic type, a spray type, a method using a fluid nozzle, and the like can be applied.
- the cover body 121 is provided with an opening / closing part 122 so that a living body can enter and exit, and an opening part 123 for exposing the head of the living body to the outside of the cover 12. Further, a supply port 124 for introducing the carbon dioxide mist into the cover main body 121 and a discharge port 125 (discharge means) for discharging the carbon dioxide mist in the cover main body 121 are provided. Further, a safety valve (relief valve) may be provided that automatically opens the valve when the pressure bath cover 12 reaches a certain pressure or higher.
- the supply port 124 is provided in communication with the cover main body 121 to introduce the carbon dioxide mist into the pressure bath cover 12, and the carbon dioxide mist generating means 113 is connected thereto through the carbon dioxide mist supply pipe 119.
- a check valve is provided in the supply port 124 to prevent the backflow of the carbon dioxide mist.
- the discharge port 125 is a vent for adjusting the internal pressure and the concentration of carbon dioxide mist by discharging the gas in the pressure bath cover 12.
- the discharge port 125 opens and closes based on a command from the control device 14.
- the control device 14 is composed of a computer having a CPU, a memory, and a display.
- the concentration of the carbon dioxide mist in the pressure bath cover 12 is set to a predetermined value or more (preferably 60% or more), and is further maintained.
- the discharge port 125 of the carbon dioxide mist generation supply unit 11 and the pressure bath cover 12 is controlled based on the measurement value of the densitometer 13.
- the temperature and pressure value in the pressure bath cover 12 may be controlled.
- the control apparatus 14 has a timer function, and enables the carbon dioxide mist pressure bath for the set time.
- the carbon dioxide mist pressure bath apparatus 20 includes a plurality (here, two as an example) of carbon dioxide mist generation and supply means 21A and 21B.
- the pressure bath cover 22 for horses is formed in such a size that the cover body 221 covers almost the whole body of the horse, and includes an opening / closing part 222 and an opening part 223, and a plurality of (here, two as an example) supply ports. 224A and 224B and a discharge port 225 are provided.
- the supply ports 224A and 224B are connected to carbon dioxide mist generation and supply means 21A and 21B, respectively.
- the carbon dioxide mist may be generated from different liquids and the action of various liquids may be exerted on the living body.
- the carbon dioxide mist pressure bath device 30 includes a carbon dioxide mist generating / supplying means 11 for generating and supplying carbon dioxide mist, and a pressure bath cover 32 for surrounding the carbon dioxide mist together with a living body (a carbon dioxide mist enclosure). Means), a densitometer 13 (concentration detecting means) for measuring the concentration of the carbon dioxide mist in the pressure bath cover 32, and the gas in the pressure bath cover 32 are discharged to the outside, and the concentration of the carbon dioxide mist is not less than a predetermined value. And a control device 14 (control means) for controlling the amount of carbon dioxide mist supplied from the carbon dioxide mist generation / supply means 11.
- FIG. 10B shows a pressure bath cover 32b for supine.
- the pressure bath cover 32b for the supine is formed in a horizontally long shape.
- the cover body 321b is provided with an opening 326b and leakage prevention means 327b. Further, a carbon dioxide mist supply port 328b, a discharge port 329b, and a door 325b for entering and exiting are provided.
- FIG. 37 is a schematic cross-sectional view showing the structure of the carbon dioxide mist generating means 130.
- the carbon dioxide mist generating means 130 stores liquid in the interior in advance, and the high-speed flow of the gas supplied from the carbon dioxide supply means 111 A gas mist obtained by pulverizing and dissolving the liquid and gas is generated, and the gas is further mixed and supplied to the pressure bath cover 12 shown in FIG.
- the carbon dioxide mist generating means 130 includes a connecting part 131 connected to the gas supplying means 111, a branching part 132 for branching the gas flow from the connecting part 131, and a liquid storing part 133 for storing liquid.
- the gas supply means 111 is connected to the connecting portion 131 directly or via a gas cord or the like.
- the structure of the connecting portion 131 is such that the gas cord connected to the gas supply means 111 or the direct gas supply means 111 can be connected with one touch, and various forms can be applied according to the gas supply means 111 to be connected. .
- the gas introduction part 138 is a gas guide path from the branch part 132 provided at the lower part of the carbon dioxide mist generating means 130 to the upper part through the side surface inside the carbon dioxide mist generating means 130, and is integrated with the carbon dioxide mist generating means 130. Is formed.
- the merging portion 137 is formed of a cylindrical member disposed so as to surround the baffle 136 on the tip opening 134 ⁇ / b> A of the nozzle 134, and communicates with the gas introduction portion 138.
- the gas branched by the branching part 132 and guided to the gas introducing part 138 merges with the gas mist generated by the joining part 137 from above and to the gas mist discharge part 139 formed around the cylindrical joining part 137. And push out the gas mist.
- the carbon dioxide mist generating means 130 may be configured to be removable from at least a part including the liquid storage part 133 and replaceable with another new liquid storage part 133.
- the carbon dioxide mist generating means 130 is assembled, and the replacement part including the liquid storage part 133 is assembled with other parts to complete the carbon dioxide mist generating means 130 integrated with the gas introduction part 138. .
- the liquid storage part 133 is made disposable and hygiene is maintained.
- the configuration for replenishing the liquid to the liquid suction pipe 135A is omitted.
- the carbon dioxide mist generating means 130 is preferably sterilized in advance at the manufacturing stage.
- the gas is guided from the gas introduction part 138 to the junction part 137 via the branch part 132, and the discharge pressure of the generated gas mist is increased.
- the generated gas mist is mixed with the gas from the branch part 132 and discharged from the gas mist outlet 139A. That is, with reference to FIG. 5, the gas mist is supplied to the pressure bath cover 12 via the carbon dioxide mist supply pipe 119.
- FIG. 38 is a schematic diagram showing an outline of a third embodiment of the carbon dioxide mist pressure bath apparatus according to the present invention.
- the pressure bath cover 150 here covers the local part of the living body (the forearm of the human body is shown as an example in FIG. 2), and forms a space in which gas mist and gas are enclosed.
- the pressure bath cover 150 includes a first cover (inner cover) 161 disposed on the inner side and a second cover (outer cover) 155 disposed on the outer side and covering the entire first cover 161 so as to be substantially sealed. And.
- the pressure bath cover 150 is preferably made of a pressure-resistant, non-breathable, moisture-impermeable material, such as natural rubber, silicon rubber, polyethylene, polypropylene, polyvinylidene chloride, polystyrene, polyvinyl acetate, It is composed of vinyl chloride, polyamide resin, polytetrafluoroethylene and the like.
- a pressure-resistant, non-breathable, moisture-impermeable material such as natural rubber, silicon rubber, polyethylene, polypropylene, polyvinylidene chloride, polystyrene, polyvinyl acetate, It is composed of vinyl chloride, polyamide resin, polytetrafluoroethylene and the like.
- the inner cover 161 is a substantially bag-shaped cover for locally covering a portion having a high gas mist absorption rate, and also functions as a heat insulating cover. That is, after the temperature of the living body cover member 150 rises with time, a relatively cold gas mist generated at room temperature is supplied, but the inner cover 161 is made of a heat insulating material so that the temperature does not rise immediately. Is preferred. By mounting the inner cover 161, it is possible to prevent vaporization of the gas mist supplied into the gas mist pressure bath.
- the inner cover 161 is particularly effective when it is attached to a part where gas mist is to be absorbed, a part where there is a large amount of sweat glands, such as the palm or the sole of the foot.
- the outer cover 155 is provided with a connecting portion 158 that is connected to the supply port 152 of the inner cover 161 and connects the inner cover 161 and the gas mist supply pipe 119 while sealing the inside of the outer cover 155.
- the outer cover 155 is preferably provided with a gas mist outlet for extracting gas mist and gas from the cover, a valve for adjusting the pressure in the cover, and the like.
- the pressure adjustment in the cover may be performed manually, but it is desirable that the pressure is adjusted automatically by the control device 160 together with the gas mist supply control based on the measurement value of the pressure gauge 171 described later.
- a safety valve (a relief valve) that automatically opens when the inside of the outer cover 155 reaches a certain pressure value or more may be provided.
- a pressure gauge 171 for measuring the internal pressure is installed in the outer cover 155.
- the control device 160 generates and supplies gas mist based on the measured value of the pressure gauge 171 in order to keep the pressure value in the outer cover 155 at 1 atmosphere or more (more preferably, 1.01 to 2.5 atmospheres). To control. For example, the supply of gas from the gas supply means 110 is adjusted and stopped, or the gas mist and gas are discharged from the inner cover 161 and the outer cover 155. In this embodiment, since the pressure bath cover 150 in which the inner cover 161 is opened by the opening 154 is used, only one pressure gauge 171 needs to be provided in the outer cover 155. Further, a thermometer 172 for measuring temperature may be installed in the inner cover 161 or the outer cover 155 (in this case, the inner cover 161). The control device 160 turns on / off the gas mist supply from the measurement value of the thermometer 172.
- sensors for measuring oxygen concentration, carbon dioxide gas concentration, humidity, and the like are installed in the pressure bath cover 150, and the control device 60 controls the environment in the cover within a range of each preset value. You may make it do.
- the control device 160 includes a computer having a CPU, a memory, and a display.
- Various controls such as pressure adjustment and on / off switching of the gas supplied from the gas supply means 110 and on / off switching of the gas mist supply are performed so that the gas mist pressure bath can be performed in an optimum state.
- each means is set so that the inside of the pressure bath cover 150 is kept in an optimum state for performing the gas mist pressure bath from the measured values of sensors such as the pressure gauge 171 and the thermometer 172 installed in the pressure bath cover 150. Adjust.
- the pressure value in the pressure bath cover 150 becomes a predetermined value or more, it is preferable that the gas supply of the gas supply means 110 is stopped by the control device 160. Note that the above adjustment may be performed manually without using the control device 160.
- Table 1 shows that each treatment with three kinds of gases, CO2 gas (CG), CO2 mist (CM), and 100% oxygen mist (OM), is performed by laser tissue blood oxygen monitor before the treatment (pre).
- the value when the average value of the measured oxyhemoglobin amount of each individual is calculated is used as a reference value, and is represented by an average value of 1.000 in the table.
- the average value of the oxyhemoglobin amount in each individual in the case of 20 minutes, 30 minutes and post from the start of the treatment was measured with a blood flow meter before the treatment (pre), and the oxyhemoglobin of each individual was measured.
- the value when the average value of the quantity is calculated is divided by the reference value, and the value is shown as the average value.
- the average value of the amount of deoxyhemoglobin in each individual in the case of 20 minutes, 30 minutes and post, and the average value of the amount of deoxyhemoglobin of each individual measured with a laser tissue blood oxygen monitor before treatment (pre)
- the calculated value is divided by the reference value, and the value is shown as an average value.
- FIG. 14 Comparison between two groups of tissue deoxygenated blood volume (deoxyhemoglobin amount) (FIG. 14)
- Part A of FIG. 14 shows a time-dependent change in the amount of deoxyhemoglobin in each treatment between the two groups of CO2 gas (CG) and CO2 mist (CM) as an interaction line graph.
- Part B and part C of FIG. Shows a decrease in the average value of the amount of deoxyhemoglobin in a state where 30 minutes have passed since the start of each treatment, as a line graph. As shown in part A of FIG.
- both CO2 gas (CG) and CO2 mist (CM) showed a tendency to decrease after 10 minutes of treatment, and CO2 mist showed a significant decrease in the amount of deoxyhemoglobin compared to CO2 gas after 30 minutes of treatment Is recognized. Further, in the comparison at 30 minutes after treatment, the deoxyhemoglobin amount was significantly decreased in both groups, and as shown in B part and C part of FIG. CM) is more prominent than CO2 gas (CG). This indicates that treatment with CO2 mist (CM) containing CO2 in the mist has a lowering effect on the amount of hemoglobin that is not bound to oxygen, that is, oxyhemoglobin, than treatment with CO2 gas (CG).
- the value when the average value of the total hemoglobin amount before the treatment is calculated is represented as a reference value with an average value of 1.000 in the table, 10 minutes have elapsed since the treatment was started, 20
- the average value of total hemoglobin in each individual in the case of minutes, 30 minutes, and post is calculated, and the average value of total hemoglobin of each individual measured with a blood flow meter before treatment (pre) Is divided by the reference value, and the value is shown as an average value.
- CM CO2 mist
- AM air mist
- CG CO2 gas
- FIG. 16 Comparison of tissue total blood volume (total hemoglobin amount) between two groups (FIG. 16)
- Part A of FIG. 16 shows the change over time of the total hemoglobin amount in each treatment between the two groups of CO 2 gas (CG) and CO 2 mist (CM) in an interactive line graph
- part B and part C of FIG. Shows a change in the average value of the total hemoglobin amount at 30 minutes after the start of treatment in a line graph.
- the CO2 mist (CM) shows a tendency that the maximum value of the total hemoglobin amount appears 10 minutes after the start of treatment and then decreases.
- CO2 mist (CM) shows a higher value than before treatment (pre).
- FIG. 18 Comparison of tissue blood oxygen saturation (StO2) between two groups (FIG. 18) Part A of FIG. 18 shows a time-dependent change in tissue blood oxygen saturation (StO2) in each treatment between the two groups of CO2 gas (CG) and CO2 mist (CM) in an interaction line graph.
- CG CO2 gas
- CM CO2 mist
- StO2 increases in tissue blood oxygen saturation (StO2) 10 minutes after the start of treatment, and is significantly different from CO2 gas (CG) 20 minutes after the start of treatment.
- Tissue blood oxygen saturation also increases in CO2 gas (CG) 10 minutes after the start of treatment, but tissue blood oxygen saturation (StO2) tends to saturate 30 minutes after the start of treatment. unacceptable.
- tissue blood oxygen saturation StO2
- CM CO2 mist.
- CG CO2 gas
- FIG. 19 shows that the CO2 mist (M) has a larger pH value change than other gases, and the tissue pH becomes acidic throughout the period from 1 week after treatment ( ⁇ 1 wks) to 3 weeks after treatment ( ⁇ 3 wks). Indicates that it is changing.
- FIG. 20 shows the interaction line graph of Table 6, with higher pH values before treatment (day 1) than without myocardial infarction (NM), CO 2 mist (M), CO 2 gas (CG), control (C). Indicates. However, the pH value decreases but other gases do not change after 2 weeks (2 wks) after the treatment of only CO 2 mist (M). Regarding the change of each gas, the CO2 mist (M) maintains a low pH as compared with other gases, and also the change is large as shown in FIG. 20, and the carbon dioxide mist pressure bath means is used to lower the pH of the individual. Optimal as gas to be sealed under pressure.
- the improvement effect of the EF is suppressed in the M + L group. This suggests that NO is involved in the effect of improving the left ventricular contractility by carbon dioxide mist therapy.
- Table 8 shows the average value of each individual group when the left ventricular end-diastolic diameter (LVDd) was measured for the C group, the M group, the M + L group, and the NM group, and FIG. 22 shows a bar graph.
- the M population shows a lower value than the NM population, and the expansion of the left ventricular end-diastolic diameter is suppressed. That is, cardiac remodeling is suppressed by carbon dioxide mist therapy, and the effect of carbon dioxide mist therapy is suppressed by L-NAME administration, suggesting the involvement of NO.
- Table 9 shows the average value of each individual group when the left ventricular end systolic diameter (LVDs) was measured for the C group, the M group, the M + L group, and the NM group, and FIG. 23 shows a bar graph.
- LLDs left ventricular end systolic diameter
- Table 12 shows the average value of each individual group when the left ventricular end-diastolic volume (EDV) was measured for the C group, the M group, the M + L group, and the NM group, and FIG. 26 shows a bar graph.
- EDV left ventricular end-diastolic volume
- FIG. 26 shows a bar graph.
- the M group showed a decrease in the left ventricular end-diastolic volume
- the L-NAME administration suppressed the effect of reducing the volume. That is, cardiac remodeling is suppressed by carbon dioxide mist therapy, and the effect of carbon dioxide mist therapy is suppressed by administration of L-NAME, suggesting the involvement of NO.
- Table 13 shows the average value of each individual group when the left ventricular end systolic volume (ESV) was measured for the C group, the M group, the M + L group, and the NM group, and FIG. 27 shows a bar graph.
- ESV left ventricular end systolic volume
- FIG. 27 shows a bar graph.
- the M group showed a decrease in the left ventricular end systolic volume, and the dose reduction effect was suppressed by L-NAME administration. That is, cardiac remodeling is suppressed by carbon dioxide mist therapy, and the effect of carbon dioxide mist therapy is suppressed by L-NAME administration, suggesting the involvement of NO.
- VEGF vascular endothelial growth factor
- Table 16 shows the average value of each individual group when vascular endothelial growth factor (VEGF) in the myocardium was measured for the C group, the M group, the M + L group, and the NM group, and FIG. 30 shows a bar graph.
- Intramyocardial VEGF was significantly increased in the M group compared to the NM group, and the increase in the expression was suppressed by L-NAME administration. That is, angiogenesis is promoted by carbon dioxide mist therapy, and the effect of carbon dioxide mist therapy is suppressed by administration of L-NAME.
- Table 17 shows the average value of each individual group when the size of myocardial infarction was measured for the M group, the M + L group, and the NM group, and FIG. 31 shows a bar graph. There was no significant difference in myocardial infarct size between the three groups. This proves that the myocardial infarction size is constant in each group, and the myocardial infarction model of this study is uniform. The effect of improving cardiac function is considered to be the effect of carbon dioxide mist, not the difference in myocardial infarction model size.
- Table 18 shows the average value of each individual group when the heart rate was measured for the C group, the M group, the M + L group, and the NM group
- FIG. 32 shows a bar graph. Although the heart rate decreases in the M + L group and the NM group as compared to the C group, no decrease in the heart rate is observed in the M group.
- Table 19 shows the average value of each individual group when systolic blood pressure was measured for the C group, the M group, the M + L group, and the NM group, and FIG. 33 shows a bar graph. There was no difference in systolic blood pressure between the groups. That is, carbon dioxide mist therapy does not affect systolic blood pressure.
- Table 20 shows the average value of each individual group when the diastolic blood pressure was measured for the C group, the M group, the M + L group, and the NM group, and FIG. 34 shows a bar graph. There was no difference in diastolic blood pressure between the groups. That is, carbon dioxide mist therapy does not affect diastolic blood pressure.
- Table 21 shows the average value of each individual group when the body weight corrected heart weight was measured for the C group, the M group, the M + L group, and the NM group
- FIG. 35 shows a bar graph.
- the CO 2 calibration curves m / Z44 was quantified CO 2 of which the measured m / Z44 and m / Z45. Then, the detected amount of CO 2 was divided by the sample amount, and the 12 CO 2 amount and 13 CO 2 amount per sample mass were obtained. Moreover, in order to correct the influence of natural isotopes (m / z45) present in CO 2 derived from respiration, the 13 CO 2 amount obtained from the 12 CO 2 amount is subtracted from the detected amount of 13 CO 2 , The amount of 13 CO 2 derived from skin absorption was calculated.
- the RSD showed a high reproducibility of less than 20% in all the samples.
- FIGS. 41 to 56 show the measurement results by EIC chromatogram in each of the 16 samples. In each figure, the upper row shows a 12 CO 2 chromatogram, and the lower row shows a 13 CO 2 chromatogram.
- the horizontal axis retention time and the vertical axis represents the amount of CO 2 peak area was measured for each chromatogram showing the concentration, measured m / Z44 (top) and m / Z45 of CO 2 (bottom) Values are quantified by a CO 2 calibration curve with m / z 44.
- Table 22 shows the quantitative results of 12 CO 2 and 13 CO 2 in each sample.
- the chromatogram of FIG. The amount of 12 CO 2 in the plasma of 1 is shown in the upper part, and the amount of 13 CO 2 is shown in the lower part.
- the quantified result is divided by the amount of plasma, and the amount of 12 CO 2 per mass of plasma obtained is Table 22 shows that 860 ⁇ g / g and the amount of 13 CO 2 is 7.6 ⁇ g / g.
- the amount of 12 CO 2 in the plasma of 1 is shown in the upper part
- the amount of 13 CO 2 is shown in the lower part
- the quantified result is divided by the amount of plasma
- Table 22 shows that is 960 ( ⁇ g / g) and 13 CO 2 is 59 ( ⁇ g / g).
- Table 22 the measurement results of 12 CO 2 and 13 CO 2 by chromatograms in untreated and 13 CO 2 mist-treated rat plasma, heart, liver and muscle tissues are shown as m / z 44.
- the amount of 12 CO 2 and the amount of 13 CO 2 per mass of plasma are shown by quantifying with a CO 2 calibration curve, and dividing the quantified result by the amount of plasma.
- Table 22 shows the quantitative results by using a CO 2 calibration curves m / Z44, 13 with respect to the CO 2, the natural isotopic present in CO 2 from respiration (m / Z45). Therefore, Table 23 shows the detected value of 13 CO 2 corrected by subtracting the natural isotope 12 CO 2 (m / z 45) present in CO 2 derived from respiration from 13 CO 2 based on the results shown in Table 22. Show.
- FIG. 57 to FIG. 62 show graphs in which the 12 CO 2 detection amount and the 13 CO 2 detection amount (correction value) are summarized for each sample and each processing method.
- Each 12 CO 2 detected amount of 2 is shown as a bar graph for each sample of plasma, heart, liver and muscle. In this graph, when the detected amount of 12 CO 2 in the untreated and 13 CO 2 mist treatments is compared, the detected amount of 12 CO 2 in each tissue shows a high tendency in the samples of the 13 CO 2 mist treated. It is not allowed.
- FIG. 1 no processing No. 2, 13 CO 2 mist treatment no. 1 and 13 CO 2 mist treatment no. 2, each 13 CO 2 detection amount (correction value) is shown as a bar graph for each sample of plasma, heart, liver and muscle. This graph shows that the amount of 13 CO 2 in each tissue is hardly detected when not treated.
- 13 CO 2 mist treatment is performed, an effective amount of 13 CO 2 is detected in each tissue of plasma, heart, liver and muscle, and carbon dioxide mist pressure bath treatment is effectively performed. ing.
- FIG. 60 is different from FIG. 59 in that the non-processing No. and the 13 CO 2 mist processing are performed.
- no processing No. 2 13 CO 2 mist treatment no. 1 and 13 CO 2 mist treatment no. 2 of 13 CO 2 detected amount is shown as a bar graph for each sample of plasma, heart, liver and muscle. This graph also shows that almost no amount of 13 CO 2 is detected in the case of non-treatment, but an effective amount of 13 CO 2 mist is detected in each tissue in the case of 13 CO 2 mist treatment.
- Table 24 summarizes similar experimental results for the specimens 1 to 4 of the rats in the untreated group and the specimens 1 to 4 of the rats in the 13 CO 2 treated group.
- the present invention relates to a carbon dioxide mist pressure bath method and carbon dioxide mist that promote blood circulation by bringing carbon dioxide into contact with the skin or mucous membrane of a living body directly or through clothing under predetermined conditions, thereby preventing, improving or treating myocardial infarction.
- the present invention relates to a pressure bath apparatus and has industrial applicability.
- Carbon dioxide mist pressure bath apparatus 11 Carbon dioxide mist generation supply means 111 Carbon dioxide supply means 112 Liquid supply means 113 Carbon dioxide mist generation means 113 'Carbon dioxide mist generation means (mist spray type) 114 Liquid storage section 115A Nozzle 115B Liquid absorption pipe 116 Baffle 117A Carbon dioxide supply section 117B Carbon dioxide introduction section 118A Carbon dioxide mist collection section 118B Carbon dioxide mist derivation section 119 Carbon dioxide mist supply pipe 12 Pressure bath cover 121 Cover body 122 Opening / closing section 123 Opening section 124 Supply port 125 Discharge port 13 Concentration meter 14 Control device 141 Flow valve 142 Switching valve 150 Pressure bath cover 151 Pressure gauge 20 Carbon dioxide mist pressure bath devices 21A and 21B Carbon dioxide mist generation supply means 22 Horse pressure bath cover 221 Cover body 222 Opening / closing portion 223 Opening portion 224A, 224B Supply port 225 Discharge port 30 Carbon dioxide mist pressure bath device 32 Pressure bath cover 321
Abstract
Description
炭酸ガスミスト圧浴手段内に加圧封入するガスの構成を、エアミスト(AM)、CO2ガス(CG)、CO2ミスト(CM)、100%酸素ミスト(OM)の4種類を使用して実験した。各ガスを炭酸ガスミスト圧浴手段内に加圧封入して処置を実施した個体数はそれぞれ13個、14個、15個、11個である。各個体は、ペントバルビタール麻酔下で8週齢雄ウィスタラットに挿管して開胸し、冠動脈左前下行枝を結紮し心筋梗塞モデルとしたものである。
図12のA部は、CO2ガス(CG)とCO2ミスト(CM)の2群間による各処置でのオキシヘモグロビン量経時的変化を交互作用折れ線グラフで示し、図12のB部とC部は、処置を開始して30分が経過した状態でのオキシヘモグロビン量の平均値の増加を折れ線グラフで示している。CO2ミスト(CM)の処置10分後にオキシヘモグロビン量は増加を認め、その増加量はCO2ガス(CG)と比較し有意差を認めている。また、20分以降もオキシヘモグロビン量増加は持続していた。また、処置30分時点の比較では、CO2ミスト(CM)は処置30分後に有意にオキシヘモグロビン量が増加しているに対して(図12のB部)、CO2ガス(CG)は有意なオキシヘモグロビン量の増加は認められていなかった(図12のC部)。このことより、ミストにCO2を含むCO2ミスト(CM)による処置はCO2ガス(CG)の処置よりもオキシヘモグロビン量の増加効果があることを示す。
図14のA部は、CO2ガス(CG)とCO2ミスト(CM)の2群間による各処置でのデオキシヘモグロビン量の経時的変化を交互作用折れ線グラフで示し、図14のB部とC部は、それぞれ処置を開始して30分が経過した状態でのデオキシヘモグロビン量の平均値の低下を折れ線グラフで示している。図14のA部が示すように、CO2ガス(CG)、CO2ミスト(CM)共に処置10分後に低下傾向を認め、処置30分後にCO2ミストはCO2ガスに比べてデオキシヘモグロビン量は有意な低下が認められる。また、処置30分時点での比較では、両群ともに有意にデオキシヘモグロビン量が有意に低下しているが、そして、図14のB部、C部が示すように、その低下率はCO2ミスト(CM)がCO2ガス(CG)よりも顕著である。このことより、ミストにCO2を含むCO2ミスト(CM)による処置はCO2ガス(CG)の処置よりも酸素と結合していないヘモグロビン、つまりオキシヘモグロビン量の低下効果があることを示す。
図16のA部は、CO2ガス(CG)とCO2ミスト(CM)の2群間による各処置での総ヘモグロビン量の経時的変化を交互作用折れ線グラフで示し、図16のB部とC部は、処置を開始して30分時点での総ヘモグロビン量の平均値の変化を折れ線グラフで示している。図16のA部が示すように、CO2ミスト(CM)は処置開始後10分で総ヘモグロビン量の最大値が現れ、その後は低下する傾向を示す。それでも、CO2ミスト(CM)は処置前(pre)と比べても高い数値を示す。それに対して、図16のB部、C部が示すように、CO2ガス(CG)は処置開始後20分で総ヘモグロビン量の最大値が現れて、その後は低下する傾向を示し、処置開始後30分で処置前(pre)より数値が低くなる。このことよりミストにCO2を含むCO2ミスト(CM)による処置はCO2ガス(CG)の処置よりも総ヘモグロビン量増加、つまり血流改善効果があることを示す。
図18のA部は、CO2ガス(CG)とCO2ミスト(CM)の2群間による各処置での組織血液酸素飽和度(StO2)の経時的変化を交互作用折れ線グラフで示し、図18のB部、C部は、各処置を開始して30分時点での組織血液酸素飽和度(StO2)の平均値を折れ線グラフで示している。CO2ミスト(CM)は処置開始後10分で組織血液酸素飽和度(StO2)は増加し、処置開始後20分でCO2ガス(CG)と有意差が認められる。CO2ガス(CG)も処置開始後10分で組織血液酸素飽和度(StO2)は増加するが、処置開始後30分で組織血液酸素飽和度(StO2)は飽和する傾向を示し、それ以降増加を認められない。また、処置30分時点での比較では、図12のB部、C部が示すように、両群ともに有意に組織血液酸素飽和度(StO2)が増加しているが、その増加率はCO2ミスト(CM)がCO2ガス(CG)よりも顕著である。
炭酸ガスミスト圧浴手段内に加圧封入するガスの構成は、コントロール(C)、心筋梗塞非処置(NM)、CO2ミスト(M)、CO2ガス(CG)の4種類を使用して実験した。各ガスにより処置を実施した個体数はそれぞれ8個、9個、8個、5個である。そして、各処置において、処置前(Δ1day)、処置後1週間経過(Δ1wks)、処置後2週間経過(Δ2wks)、処置後3週間経過(Δ3wks)での各個体のpHの変化を測定する。
(1.1)測定条件の設定
(1.1.1)標準溶液の調製
炭酸ナトリウムを水に溶解して、任意の濃度の溶液を調整し、この一定量を測定用バイアルに採り、硫酸を加え密閉する。測定用バイアル内の炭酸量は、10、50、100、250、500μgの5水準とし、これら操作は、窒素ガス雰囲気のグローブボックス内で行った。
測定用バイアルの気相部を、以下の条件にてガスクロマトグラム質量分析計にて測定した。
<測定条件>
・カラム:Pora BOND Q 長さ25m・内径0.25mm・膜厚3μmm
・カラム温度:40°C(8分)
・キャリアガス:He
・試料注入法:ヘッドスペース法(60°C、1分間加熱)
・イオン化法:電子衝撃イオン化法(EI法:70eV)
・測定モード:選択イオンモニタリング(SIM)
・モニターイオン:定量イオン m/z44(12CO2)、m/z4513CO2)
標準溶液を測定し、濃度(μg/バイアル)を縦軸に、m/z44の抽出イオンカレント(EIC)クロマトグラムから検出されたCO2のピーク面積を横軸にプロットして検量線を作成した。
(1.2.1)前処理方法
試料に水酸化ナトリウム溶液を加え解凍後、乳鉢で均一にし、この一定量を測定用バイアルに採り硫酸を加え密閉した。これら操作は、窒素ガス雰囲気のグローブボックス内で行った。乳鉢で均一にした後の動作は1試料につき1乃至3回繰り返した。
前処理後の測定用バイアルの試料の測定後、m/z44のCO2検量線により、測定したm/z44及びm/z45のCO2を定量した。そして、CO2の検出量を試料量で除し、試料質量当たりの12CO2量及び13CO2量を求めた。
また、呼吸由来のCO2中に存在する天然同位体(m/z45)の影響を補正するために、12CO2量から求めた13CO2量を、13CO2の検出量から差し引いて、皮膚吸収由来の13CO2量を算出した。
(2.1)測定条件の妥当性
(2.1.1)検量線の直線性
図39は、測定したEICクロマトグラムで、上段は12CO2量、下段は13CO2量のクロマトグラムである。クロマトグラムは、横軸が保持時間、縦軸が濃度を示し、正規分布の三角形状部分の面積(ピーク面積)が測定されたCO2の量となる。図40は、作成した12CO2の検量線を示すもので、相関係数(R)が0.9987と直線に近似した二次曲線の検量線である。
炭酸量が500μgの標準溶液の繰り返し測定の結果、日内再現性は相対標準偏差(RSD)が3乃至5%、試料測定間(10日間)再現性はRSDが11%であった。
図41から図56までは16通りの各試料におけるEICクロマトグラムによる測定結果を示している。各図において、上段は12CO2のクロマトグラムを示し、下段は13CO2のクロマトグラムを示している。
13CO2検出量(補正値)=13CO2検出量-12CO2検出量×0.0113/0.984
11 炭酸ガスミスト発生供給手段
111 炭酸ガス供給手段
112 液体供給手段
113 炭酸ガスミスト生成手段
113′ 炭酸ガスミスト生成手段(霧吹き式)
114 液体貯留部
115A ノズル
115B 吸液管
116 バッフル
117A 炭酸ガス供給部
117B 炭酸ガス導入部
118A 炭酸ガスミスト収集部
118B 炭酸ガスミスト導出部
119 炭酸ガスミスト供給管
12 圧浴用カバー
121 カバー本体
122 開閉部
123 開口部
124 供給口
125 排出口
13 濃度計
14 制御装置
141 流量バルブ
142 切替弁
150 圧浴用カバー
151 圧力計
20 炭酸ガスミスト圧浴装置
21A、21B 炭酸ガスミスト発生供給手段
22 馬用の圧浴用カバー
221 カバー本体
222 開閉部
223 開口部
224A、224B 供給口
225 排出口
30 炭酸ガスミスト圧浴装置
32 圧浴用カバー
321 カバー本体
322 上部
323 底部
324 側部
325 扉
325A 取手
326 開口
327 漏出防止手段
327A 開口
328 供給口
329 排出口
32a 立位用の圧浴用カバー
32b 仰臥用の圧浴用カバー
321a、321b カバー本体
325a、325b 扉
326a、326b 開口
327a、327b 漏出防止手段
328a、328b 供給口
329a、329b 排出口
330 椅子
Claims (16)
- 炭酸ガスを生体の皮膚及び粘膜に直接又は被服を通して接触させることにより心筋領域の血行を改善又は促進させ、以って心筋梗塞を予防、改善又は治療する炭酸ガスミスト圧浴方法であって、
(a)炭酸ガスを液体に粉砕溶解させこれを霧状にした炭酸ガスミストを発生させるステップと、
(b)生体を密閉状態に包囲する炭酸ガスミスト包囲手段内に、前記炭酸ガスミストを噴霧するステップと、
(c)前記炭酸ガスミスト包囲手段内の気体が大気圧よりも高い所定値以上を維持するように、必要に応じて、前記ステップ(b)と並行して、前記炭酸ガスミスト包囲手段内の気体を外部に排出させるステップと、
(d)前記炭酸ガスミスト包囲手段内に対する前記炭酸ガスミストの供給を少なくとも20分間継続するステップと、
前記ステップ(a)乃至(d)による炭酸ガスミストの圧浴を、少なくとも1日一回4週間継続するステップと、
の各ステップを有することを特徴とする炭酸ガスミスト圧浴方法。 - 前記ステップ(d)は、前記炭酸ガスミスト包囲手段内における炭酸ガスミストの濃度を計測しつつ、前記炭酸ガスミストの濃度が所定値以上になるように前記炭酸ガスミストの供給を少なくとも20分間継続するステップ、であることを特徴とする請求項2に記載の炭酸ガスミスト圧浴方法。
- 前記ステップ(d)において、前記炭酸ガスミスト包囲手段内における気圧が所定値になるように前記炭酸ガスミストの供給量を制御する、ことを特徴とする請求項1又は2に記載の炭酸ガスミスト圧浴方法。
- 前記炭酸ガスミストは、その粒径が10μメートル以下の炭酸ガスミストを含有することを特徴とする請求項2に記載の炭酸ガスミスト圧浴方法。
- 前記ステップ(d)における前記炭酸ガスミスト包囲手段内における炭酸ガスミストの濃度は60%以上である、ことを特徴とする請求項4に記載の炭酸ガスミスト圧浴方法。
- 前記ステップ(c)における前記炭酸ガスミスト包囲手段内の気圧は、1.01乃至2.5気圧であることを特徴とする請求項3に記載の炭酸ガスミスト圧浴方法。
- 炭酸ガスを生体の皮膚及び粘膜に直接又は被服を通して接触させることにより心筋領域の血行を改善又は促進させ、以って心筋梗塞を予防、改善又は治療する炭酸ガスミスト圧浴装置であって、
生体を密閉状態に包囲するための炭酸ガスミスト包囲手段と、
炭酸ガスを液体に粉砕溶解させこれを霧状にした炭酸ガスミストを発生させ、当該炭酸ガスミストを前記炭酸ガスミスト包囲手段内に供給する炭酸ガスミスト発生供給手段と、
前記炭酸ガスミスト包囲手段内の気体を外部に排出させるための排出手段と、
前記炭酸ガスミスト包囲手段内の気体を外部に排出させつつ、必要に応じて、前記炭酸ガスミスト包囲手段内の気圧が所定値範囲内になるように前記炭酸ガスミスト発生供給手段からの前記炭酸ガスミストの供給量を制御する制御手段と、
の各手段を備えたことを特徴とする炭酸ガスミスト圧浴装置。 - 前記炭酸ガスミスト包囲手段内における炭酸ガスミストの濃度を計測する濃度検知手段と、をさらに備え、
前記制御手段は、前記炭酸ガスミストの濃度が所定値以上になるように前記炭酸ガスミストの供給量を制御する、ことを特徴とする請求項7に記載の炭酸ガスミスト圧浴装置。 - 前記炭酸ガスミスト包囲手段内における気圧を計測する気圧検知手段と、をさらに備え、
前記制御手段は、前記炭酸ガスミスト包囲手段内における気圧が所定値になるように前記炭酸ガスミストの供給量を制御する、ことを特徴とする請求項8に記載の炭酸ガスミスト圧浴装置。 - 前記炭酸ガスミスト発生供給手段は、その粒径が10μメートル以下の炭酸ガスミストを発生させることを特徴とする請求項7に記載の炭酸ガスミスト圧浴装置。
- 前記制御手段は、前記炭酸ガスミスト包囲手段内における炭酸ガスミストの濃度を60%以上に維持することを特徴とする請求項7に記載の炭酸ガスミスト圧浴装置。
- 前記制御手段は、前記炭酸ガスミスト包囲手段内の気圧を、1.01乃至2.5気圧に維持することを特徴とする請求項9に記載の炭酸ガスミスト圧浴装置。
- 前記炭酸ガスミスト包囲手段は、前記炭酸ガスミストを内部に封印する空間を形成する、折り畳み可能なカバータイプ、袋体タイプ又は固定据置型のボックスタイプの何れかの包囲手段である請求項7に記載の炭酸ガスミスト圧浴装置。
- 前記炭酸ガスミスト包囲手段は、
その内部に前記炭酸ガスミストを導入するための、内部に逆止弁を有する炭酸ガスミスト供給口と、
内部の気体を排出するための排出口と、
生体が出入りするための出入口と、前記ボックス本体内から生体の頭部を露出させるための開口と、
を備えることを特徴とする請求項13に記載の炭酸ガスミスト圧浴装置。 - 前記開口には、当該開口と生体の隙間からの炭酸ガスミストの漏出を防ぐ漏出防止手段を設けることを特徴とする請求項14に記載の炭酸ガスミスト圧浴装置。
- 前記ボックスタイプの炭酸ガスミスト包囲手段は、その内部に椅子を備えることを特徴とする請求項13に記載の炭酸ガスミスト圧浴装置。
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EP11850835.7A EP2586417A4 (en) | 2010-12-20 | 2011-12-20 | CARBON DIOXIDE GAS NOSE PRESSURE BATHING METHOD AND CARBON DIOXIDE GAS NOSE PRESSURE PRESSURE DEVICE FOR PREVENTING, TREATING AND TREATING MYOKARD INFARTS |
KR1020127032789A KR20130128309A (ko) | 2010-12-20 | 2011-12-20 | 심근 경색을 예방, 개선 또는 치료하기 위한 탄산 가스 미스트 압욕 방법 및 탄산 가스 미스트 압욕 장치 |
US13/701,748 US9271894B2 (en) | 2010-12-20 | 2011-12-20 | Carbon dioxide gas mist pressure bath apparatus for preventing, improving or curing myocardial infarction |
CN201180030969.8A CN102958489B (zh) | 2010-12-20 | 2011-12-20 | 用于预防、改善或治疗心肌梗塞的二氧化碳雾压浴方法以及二氧化碳雾压浴装置 |
BR112012032385A BR112012032385A2 (pt) | 2010-12-20 | 2011-12-20 | método e aparelho de banho de pressão de névoa de gás de dióxido de carbono |
JP2012549824A JPWO2012086635A1 (ja) | 2010-12-20 | 2011-12-20 | 心筋梗塞を予防、改善又は治療するための炭酸ガスミスト圧浴方法及び炭酸ガスミスト圧浴装置 |
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EP (1) | EP2586417A4 (ja) |
JP (1) | JPWO2012086635A1 (ja) |
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CN105848624B (zh) * | 2013-10-24 | 2018-04-10 | Bsn医疗有限公司 | 浸渍装置 |
KR101703530B1 (ko) | 2015-11-27 | 2017-02-07 | 박무학 | 각도 조절이 가능한 휴대용 테라피 장치 |
CN106983608A (zh) * | 2017-03-21 | 2017-07-28 | 王志美 | 一种专用于心脏病患者的老年护理椅 |
KR101935830B1 (ko) * | 2018-02-13 | 2019-01-07 | 주식회사 오스테오시스 | 외부역박동시스템과 그 제어방법 |
US11377867B2 (en) * | 2019-12-20 | 2022-07-05 | Patricia Wanchun Lee Liu | Heat reflection tent |
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EP2586417A4 (en) | 2014-03-12 |
KR20130128309A (ko) | 2013-11-26 |
EP2586417A1 (en) | 2013-05-01 |
BR112012032385A2 (pt) | 2016-11-08 |
JPWO2012086635A1 (ja) | 2014-05-22 |
CN102958489A (zh) | 2013-03-06 |
US9271894B2 (en) | 2016-03-01 |
CN102958489B (zh) | 2015-09-09 |
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