WO2015001964A1 - 経皮吸収用気体製造装置、経皮吸収用気体製造方法、及び経皮吸収用気体 - Google Patents
経皮吸収用気体製造装置、経皮吸収用気体製造方法、及び経皮吸収用気体 Download PDFInfo
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- WO2015001964A1 WO2015001964A1 PCT/JP2014/066243 JP2014066243W WO2015001964A1 WO 2015001964 A1 WO2015001964 A1 WO 2015001964A1 JP 2014066243 W JP2014066243 W JP 2014066243W WO 2015001964 A1 WO2015001964 A1 WO 2015001964A1
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- carbon dioxide
- gas
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- floating
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M13/00—Insufflators for therapeutic or disinfectant purposes, i.e. devices for blowing a gas, powder or vapour into the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
- A61H33/00—Bathing devices for special therapeutic or hygienic purposes
- A61H33/14—Devices for gas baths with ozone, hydrogen, or the like
- A61H2033/145—Devices for gas baths with ozone, hydrogen, or the like with CO2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
- A61H2201/00—Characteristics of apparatus not provided for in the preceding codes
- A61H2201/02—Characteristics of apparatus not provided for in the preceding codes heated or cooled
- A61H2201/0207—Characteristics of apparatus not provided for in the preceding codes heated or cooled heated
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/22—Gas releasing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/87—Application Devices; Containers; Packaging
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/02—Gases
- A61M2202/0225—Carbon oxides, e.g. Carbon dioxide
Definitions
- the present invention relates to a device and method for producing a gas for percutaneous absorption for allowing an animal or human to absorb carbon dioxide percutaneously, and the device and a gas for percutaneous absorption produced by the method. is there.
- Patent Document 1 It is already known that when carbon dioxide is taken into the human body by percutaneous absorption, various symptoms are improved in terms of medical care and beauty (see Patent Document 1).
- the main mechanism of action of carbon dioxide at that time is a vasodilatory action and a tissue oxygen partial pressure increasing action (see Non-Patent Document 1). Therefore, the effect of carbon dioxide can be predicted by the presence and extent of redness of the skin, which reflects the vasodilatory effect.
- the present inventor has already proposed various carbon dioxide external preparations in which carbon dioxide is continuously generated in a viscous composition adhering to the skin (See Patent Documents 3 to 7). Furthermore, the present inventor supplies a carbon dioxide into a hermetic envelope that can seal the body surface from the outside air in order to percutaneously absorb carbon dioxide from a wide range of skin, and to supply carbon dioxide inside the hermetic envelope.
- a device that includes a supply device that absorbs carbon dioxide and assists percutaneous absorption of carbon dioxide inside the hermetic enclosure (see Patent Document 8).
- Patent Documents 9 to 19 disclose a method for transdermally absorbing carbon dioxide using gaseous carbon dioxide.
- the present invention is a transdermal absorption gas that can be easily applied to clothes and the skin hidden in clothes, etc. without wetting the clothes and the skin, and can exert a remarkable effect by percutaneous absorption of carbon dioxide.
- the purpose is to get.
- the percutaneous absorption gas production apparatus of the present invention is an apparatus for producing a transdermal absorption gas containing a gaseous carbon dioxide solvent complex, and a carbon dioxide supply unit for supplying gaseous carbon dioxide;
- the vaporous solvent that can dissolve the carbon dioxide, the solvent vapor generation unit that generates a vapor, and the supplied carbon dioxide and the generated solvent vapor are mixed to form a gas
- a transdermal absorption gas generating unit that generates a transdermal absorption gas containing a carbon dioxide solvent complex and (1) a suspended droplet of the solvent from the generated percutaneous absorption gas Or a floating droplet removing unit for removing the solvent, or (2) a mixture preventing means for preventing the solvent droplets from being mixed into the generated gas for percutaneous absorption. It is characterized by containing.
- the transdermal absorption gas production method of the present invention is a method for producing a transdermal absorption gas containing a gaseous carbon dioxide solvent complex, and a carbon dioxide supply step for supplying gaseous carbon dioxide;
- the gas phase is formed by mixing the carbon dioxide-dissolvable and vaporizable solvent vapor generating step, and the supplied carbon dioxide and the solvent vapor generated are mixed.
- the method further comprises a step of removing a suspended droplet that removes the droplet, or 2) preventing the suspended droplet of the solvent from being mixed into the generated transdermal absorption gas. It is characterized by including a process.
- the percutaneous absorption gas of the present invention is obtained by using the percutaneous absorption gas production apparatus or by the percutaneous absorption gas production method.
- the carbon dioxide solvent complex has a molecular structure equivalent to dissolved carbon dioxide in that carbon dioxide molecules and solvent molecules are reversibly bonded, the present inventors have passed the same process as dissolved carbon dioxide. Expected to be absorbed into the skin. On the other hand, when the percutaneous absorption gas containing a carbon dioxide solvent complex contains a lot of solvent droplets, the carbon dioxide is absorbed into the suspension droplets to form dissolved carbon dioxide (see Patent Documents 9 to 19). ).
- the present inventor when the gas for percutaneous absorption containing a carbon dioxide solvent complex does not contain suspended droplets of the solvent, can effectively exert the effect of percutaneous absorption of carbon dioxide, And the present invention was completed.
- solvent droplets mean solvent fine particles floating in the air and having a diameter of approximately 100 ⁇ m or less.
- the solvent vapor means a gas in which solvent molecules are basically separated one by one.
- the suspended droplets of the solvent are removed from the transdermal absorption gas obtained by the percutaneous absorption gas generation unit by the floating droplet removal unit.
- the percutaneous absorption gas does not contain floating droplets.
- the mixture liquid preventing droplets are prevented from being mixed with the percutaneous absorption gas obtained by the percutaneous absorption gas generation unit by the mixing prevention means. Therefore, the obtained gas for transdermal absorption does not contain floating droplets. That is, according to the percutaneous absorption gas production apparatus of the present invention, it is possible to obtain a percutaneous absorption gas that does not contain suspended droplets of a solvent.
- the suspended droplets of the solvent are removed from the transdermal absorption gas generated through the percutaneous absorption gas generation step by the floating droplet removal step.
- the percutaneous absorption gas does not contain floating droplets.
- the solvent droplets are mixed into the transdermal absorption gas generated in the transdermal absorption gas generation step by the mixing prevention step. Therefore, the percutaneous absorption gas does not contain floating droplets. That is, according to the method for producing a gas for percutaneous absorption of the present invention, a gas for percutaneous absorption that does not contain suspended droplets of a solvent can be obtained.
- the gas for percutaneous absorption of the present invention since it does not contain solvent droplets, high concentration of carbon dioxide can be absorbed percutaneously without depending on the solubility of carbon dioxide in the solvent. Therefore, the following effects can be exhibited. (1) The effect of percutaneous absorption of carbon dioxide can be improved easily and significantly. (2) It can be realized that carbon dioxide is easily absorbed percutaneously from a wide range of skin. (3) Carbon dioxide can be absorbed through the skin without wetting the clothes and the skin. (4) It is possible to realize that carbon dioxide is easily absorbed percutaneously from the skin hidden by clothes or the like.
- FIG. 7 is a schematic side sectional view of a manufacturing apparatus used in Example 1.
- FIG. 5 is a partially omitted plan view of the apparatus of FIG. 4.
- 1 is a schematic side sectional view of a manufacturing apparatus used in Examples 2 to 10.
- 10 is a schematic side sectional view of a manufacturing apparatus used in Example 11.
- FIG. 8 is a partially omitted plan view of the apparatus of FIG. 7.
- the percutaneous absorption gas production apparatus of the present invention can be roughly classified into two types.
- the first apparatus includes a suspended droplet removing unit that removes suspended droplets of a solvent from the generated gas for percutaneous absorption.
- the second apparatus includes a mixing prevention means for preventing floating droplets of the solvent from being mixed into the generated percutaneous absorption gas.
- a first percutaneous absorption gas production apparatus is an apparatus for producing a transdermal absorption gas containing a gaseous carbon dioxide solvent complex, and a carbon dioxide supply unit for supplying gaseous carbon dioxide; Solvent and vaporizable solvent vapor generating solvent vapor generating section, mixed with the supplied carbon dioxide and generated solvent vapor to form a gaseous carbon dioxide solvent composite
- a percutaneous absorption gas generation unit that generates a transdermal absorption gas containing the body, and removes floating droplets of the solvent from the generated percutaneous absorption gas. Is further provided.
- the floating droplet removal unit can be roughly divided into two types.
- the first suspended droplet removing unit has a heating means for evaporating the suspended droplets contained in the transdermal absorption gas.
- the second floating droplet removing unit has an adsorbing means for adsorbing the floating droplets contained in the transdermal absorption gas.
- the adsorption means is a chemical adsorbent or a physical adsorbent.
- a second transdermal absorption gas production apparatus is an apparatus for producing a transdermal absorption gas containing a gaseous carbon dioxide solvent complex, and a carbon dioxide supply unit for supplying gaseous carbon dioxide; Solvent and vaporizable solvent vapor generating solvent vapor generating section, mixed with the supplied carbon dioxide and generated solvent vapor to form a gaseous carbon dioxide solvent composite
- a percutaneous absorption gas generating section that generates a transdermal absorption gas containing the body, and prevents the solvent droplets from being mixed into the generated percutaneous absorption gas. It is characterized by including mixing prevention means.
- the mixing prevention means includes: a carbon dioxide supply unit configured to supply carbon dioxide that does not include floating droplets; and a solvent vapor generation unit configured to generate solvent vapor that does not include floating droplets. is there.
- the carbon dioxide supply unit is configured to vaporize and supply liquefied carbon dioxide.
- the carbon dioxide supply unit has a heating means for evaporating floating droplets contained in the carbon dioxide.
- the carbon dioxide supply unit has an adsorbing means for adsorbing floating droplets contained in carbon dioxide.
- the solvent vapor generation unit has a heating means for heating the solvent so that the vapor pressure is equal to or lower than the saturated vapor pressure at the temperature.
- the solvent vapor generation unit has an adsorption unit that adsorbs floating droplets contained in the solvent vapor.
- the method for producing a gas for percutaneous absorption according to the present invention can be roughly classified into two types.
- the first method includes a suspended droplet removing step of removing suspended droplets of the solvent from the generated gas for percutaneous absorption.
- the second method includes a mixing prevention step for preventing the suspended droplets of the solvent from being mixed into the generated gas for percutaneous absorption.
- a first transdermal absorption gas production method is a method of producing a transdermal absorption gas containing a gaseous carbon dioxide solvent complex, and a carbon dioxide supply step for supplying gaseous carbon dioxide; Solvent vaporizable, vaporizable, solvent vapor generating step, solvent vapor generation step, and carbon dioxide solvent composite in gaseous form by mixing the supplied carbon dioxide with the generated solvent vapor A percutaneous absorption gas generating step for generating a percutaneous absorption gas containing the body, and removing the floating droplets of the solvent from the generated percutaneous absorption gas.
- the method further includes a process.
- the floating droplet removal process can be roughly divided into two types.
- the first floating droplet removing step has a heating step for evaporating the floating droplets contained in the transdermal absorption gas.
- the second suspended droplet removing step has an adsorption step for adsorbing suspended droplets contained in the transdermal absorption gas.
- the adsorption step is performed using a chemical adsorbent or a physical adsorbent.
- the second method for producing a gas for percutaneous absorption is a method for producing a gas for percutaneous absorption, which includes a gaseous carbon dioxide solvent complex, and a carbon dioxide supplying step for supplying gaseous carbon dioxide; Solvent vaporizable, vaporizable, solvent vapor generating step, solvent vapor generation step, and carbon dioxide solvent composite in gaseous form by mixing the supplied carbon dioxide with the generated solvent vapor
- a percutaneous absorption gas generating step for generating a transdermal absorption gas containing the body, and preventing the suspended droplets of the solvent from being mixed into the generated percutaneous absorption gas. Including a mixing prevention step.
- the mixing prevention process is a carbon dioxide supply process for supplying carbon dioxide that does not include floating droplets, and a solvent vapor generation process that generates solvent vapor that does not include floating droplets.
- the carbon dioxide supply step vaporizes and supplies liquefied carbon dioxide.
- the carbon dioxide supply step has a heating step of evaporating floating droplets contained in the carbon dioxide.
- the carbon dioxide supply step has an adsorption step of adsorbing floating droplets contained in carbon dioxide.
- generation process has a heating process which heats a solvent so that it may become a vapor pressure below the saturated vapor pressure in the temperature.
- the solvent vapor generation step has an adsorption step of adsorbing floating droplets contained in the solvent vapor. The adsorption step is performed using a chemical adsorbent or a physical adsorbent.
- the obtained gas for percutaneous absorption must have as few floating droplets as possible, but the floating droplets need not be completely eliminated, and carbon dioxide is absorbed into the floating droplets. It is sufficient that the ratio of dissolved carbon dioxide is small.
- the gas for percutaneous absorption is (a) always kept at a temperature above room temperature, (b) the vapor pressure of the solvent is below the saturated vapor pressure, (C) It is preferable that there are few solid particles, such as dust, which accelerate
- the obtained percutaneous absorption gas contains carbon dioxide in an amount of 15% by volume or more, and the vapor pressure of the solvent may be 30% or more of the saturated vapor pressure, and preferably has a temperature of 25 ° C. or more.
- the carbon dioxide content of the transdermal absorption gas is more preferably 30% by volume or more, and most preferably 50% by volume or more.
- the vapor pressure of the solvent is more preferably 50% or more of the saturated vapor pressure, and most preferably 70% or more.
- this inventor has clarified that the percutaneous absorption efficiency of a carbon dioxide falls, when skin temperature is 25 degrees C or less.
- (Floating droplet confirmation method) The following method (a), (b), or (c) can be employed. However, it is not limited to these.
- B The presence of the Tyndall phenomenon is observed with the naked eye. If no suspended droplets are included, the Tyndall phenomenon is not observed. Specifically, a bundle of light is applied to an object in a dark sealed container, and the presence or absence of a light path is observed. If no light passage is observed, it can be determined that there are no suspended droplets.
- the floating droplets are adsorbed on the sheet and stains are formed.
- a sheet made of a material having high thermal conductivity such as metal even if there are no floating droplets, takes the heat of the vapor and condenses the solvent when it comes into contact with the vapor of the solvent.
- a stain is made on the sheet, which is not preferable.
- a method of quantifying floating droplets a method of exposing a sheet (for example, filter paper) made of a material with low thermal conductivity that adsorbs floating droplets to an object for a certain period of time and measuring the adsorption amount, Can be adopted. Specifically, it is as follows. (1) First, the total mass of the filter paper and the non-breathable aluminum pouch is measured to obtain a first measured value. (2) Next, after exposing the filter paper to the object for a certain period of time, it is immediately put in an aluminum pouch and sealed. And the total mass is measured and a 2nd measured value is obtained.
- the filter paper since the solvent which is a floating droplet is vaporizable, the floating droplet adsorbed on the filter paper is vaporized from the filter paper with time. Therefore, in order to accurately measure the amount of suspended droplets adsorbed, the filter paper must be placed in an aluminum pouch and sealed “immediately” after exposure. (3) On the other hand, since the filter paper also adsorbs solvent vapor (water vapor if the solvent is water), the filter paper is exposed to solvent vapor having a humidity at the same temperature as the object for a certain period of time, and then immediately after the aluminum pouch Seal in. And the total mass is measured and a 3rd measured value is obtained. (4) Then, the difference between the third measurement value and the first measurement value is subtracted from the difference between the second measurement value and the first measurement value. Thereby, the mass of the floating droplet adsorbed on the filter paper is obtained.
- solvent Any solvent can be used without particular limitation as long as it can dissolve gaseous carbon dioxide, is liquid at room temperature, and has vaporization properties. Specifically, an inorganic solvent or an organic solvent can be used.
- water is preferable.
- water tap water, distilled water, membrane filtered water, ion-exchanged water, electrolyzed water and the like can be used, and are not particularly limited.
- Organic solvents include monohydric alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butyl alcohol, isobutyl alcohol, sec-butyl alcohol, ter-butyl alcohol; 1,3-butylene glycol, ethylene glycol, diethylene glycol , Dihydric alcohols such as propylene glycol; glycol ethers such as 2-phenoxyethanol can be used.
- monohydric alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butyl alcohol, isobutyl alcohol, sec-butyl alcohol, ter-butyl alcohol
- 1,3-butylene glycol ethylene glycol, diethylene glycol
- Dihydric alcohols such as propylene glycol
- glycol ethers such as 2-phenoxyethanol
- the solvent water is most preferable.
- the pH is not particularly limited, but is preferably less than 7. This is because, when water is alkaline, carbon dioxide is consumed by being converted into bicarbonate ions, carbonate ions, etc. in water, so the amount of carbon dioxide solvent complex is reduced. It is.
- the acidic substance an organic acid or an inorganic acid can be used without particular limitation. Alternatively, acidic electrolyzed water may be used as water.
- the carbon dioxide source that generates carbon dioxide is not particularly limited, and liquefied carbon dioxide, dry ice, and the like can be used. Further, for example, carbon dioxide may be generated by a reaction between an acid and a carbonate. Among these, liquefied carbon dioxide is preferable because it has few impurities such as moisture and hardly contains floating droplets. It is preferable to use liquefied carbon dioxide under reduced pressure using a regulator. Moreover, since low temperature carbon dioxide gas usually comes out from the regulator, it is preferable to use it with heating.
- adsorbent As the adsorbent, a chemical adsorbent and a physical adsorbent can be used.
- the chemical adsorbent calcium chloride, magnesium sulfate, diphosphorus pentoxide, concentrated sulfuric acid, magnesium perchlorate, or the like can be used.
- the physical adsorbent zeolite, silica gel, aluminum oxide, activated carbon, cotton, molecular sieve, or the like can be used. These adsorbents can be used similarly not only when the solvent is water but also when the solvent is alcohol or fat. It is preferable to use an adsorbent suitable for the physical properties of the solvent. More specifically, for example, the solvent and the adsorbent are a combination that does not cause a chemical reaction.
- Carbon dioxide without floating droplets Carbon dioxide that does not contain suspended droplets can be obtained as follows.
- A The liquefied carbon dioxide is depressurized using a regulator. Since liquefied carbon dioxide does not contain moisture or the like and has high purity, it has almost no suspended droplets when vaporized.
- B Remove floating droplets from carbon dioxide containing floating droplets. As a method for removing the floating droplet, for example, there are an adsorption method and a heating method.
- (b-1) Adsorption method For example, when so-called dry ice is used, carbon dioxide generated from dry ice cools and condenses water vapor in the air, so that floating droplets (white smoke) are generated. Therefore, carbon dioxide generated from dry ice is exposed to the adsorbent. Thereby, the floating droplet contained in carbon dioxide is adsorbed by the adsorbent and removed. As the adsorbent, those described above can be used. Carbon dioxide generated by fermentation of microorganisms can be used after being treated in the same manner as dry ice.
- Specific heating methods include (i) a method of irradiating carbon dioxide containing floating droplets with heat rays such as infrared rays and far infrared rays, and (ii) a carbon dioxide containing floating droplets with an electric heater. A method of contacting a high temperature body such as can be adopted. Note that the heating method is not limited to the above-described method as long as it is not a method of causing a chemical change in carbon dioxide or a solvent.
- the heating temperature may be room temperature or higher, but if the temperature is too high, the obtained gas for percutaneous absorption causes burns to the human body or the like. It is preferable to set the temperature to be equal to or lower than ° C. According to the study of the present inventor, it has been found that when the skin temperature is lower than 25 ° C., it is difficult to percutaneously absorb carbon dioxide. Therefore, the heating temperature is preferably set so that the temperature of the transdermal absorption gas obtained after heating is 25 ° C. or higher.
- the solvent vapor that does not contain suspended droplets can be obtained as follows.
- the solvent is heated so as to have a vapor pressure equal to or lower than the saturated vapor pressure at that temperature.
- the temperature of the heating source is preferably equal to or higher than the boiling point of the solvent in order to efficiently generate the solvent vapor.
- the upper limit of the temperature of the heating source is naturally a temperature at which the solvent does not decompose, but is allowed to a temperature approximately 50 ° C. higher than the boiling point of the solvent.
- the solvent is water, the solvent is preferably heated to 100 ° C. or higher and 150 ° C. or lower.
- the vapor pressure of the obtained solvent vapor must be lower than the saturated vapor pressure of the solvent at that temperature.
- the humidity may be 100% or less. Even if the vapor pressure is equal to or lower than the saturated vapor pressure, the saturated vapor pressure decreases as the temperature decreases, and the solvent vapor is likely to condense and generate floating droplets. Therefore, it is preferable to further heat the solvent vapor after it is obtained so that the temperature does not drop.
- the solvent is water
- 1 ml of water is dropped on a metal plate heated to 120 ° C. for 2 seconds at intervals of 2 minutes per 4 cm 2 of the metal plate.
- the solvent vapor is preferably produced in a closed container. At this time, it is preferable to maintain the temperature of the inner wall of the container at a temperature equal to or higher than the temperature of the solvent vapor so that the solvent vapor does not cool.
- the heating temperature is preferably equal to or higher than the temperature of the solvent vapor. Specifically, the heating temperature is preferably set so that the temperature of the gas for percutaneous absorption obtained after heating is 100 ° C. or lower, and is further set to be 50 ° C. or lower. Is more preferable.
- the temperature of the gas for percutaneous absorption obtained after heating is preferably 25 ° C. or higher. It is also preferable to heat the inner wall of the mixing container itself. Furthermore, it is preferable to prevent a temperature drop of the mixed gas by using a heat insulating material on the outer wall of the mixing container.
- FIG. 1 is a schematic configuration diagram showing an example of the first percutaneous absorption gas production apparatus of the present invention.
- the apparatus 10A includes a carbon dioxide supply unit 1, a solvent vapor generation unit 2, and a suspended droplet removal unit 4.
- the solvent vapor generation unit 2 also serves as a transdermal absorption gas generation unit.
- the carbon dioxide supply unit 1 includes a cylinder 11 that contains liquefied carbon dioxide, a regulator 12, and a delivery tube 13.
- the carbon dioxide supply unit 1 decompresses the carbon dioxide from the cylinder 11 by the regulator 12 and supplies the carbon dioxide to the solvent vapor generation unit 2 through the delivery tube 13.
- the solvent vapor generation unit 2 includes a tank 21 that stores the solvent 20, an air stone 22 installed in the tank 21, and a delivery tube 23.
- the tank 21 is a sealed container.
- the delivery tube 13 is connected to the air stone 22.
- the amount of the solvent 20 is set so that the liquid level 201 of the solvent 20 is located above the air stone 22 and below the inlet end 231 of the delivery tube 23.
- the floating droplet removing unit 4 includes a sealed container 41, a heater 42 installed in the sealed container 41, and a delivery tube 43.
- the delivery tube 23 communicates with the sealed container 41.
- the apparatus 10A having the above-described configuration operates as follows. (1) The carbon dioxide supply unit 1 is operated, and gaseous carbon dioxide is supplied to the air stone 22. (2) From the air stone 22, fine bubbles of carbon dioxide are vigorously released into the solvent 20. Then, the bubbles reach the liquid surface 201 of the solvent 20 and are ruptured, whereby a floating droplet of the solvent 20 is generated in the tank 21. On the other hand, since the solvent 20 is vaporizable, vapor of the solvent 20 is also generated in the tank 21. (3) In the tank 21, carbon dioxide and the vapor of the solvent 20 are mixed, and a transdermal absorption gas containing a carbon dioxide solvent complex formed by combining the two is generated. This percutaneous absorption gas also includes suspended droplets of the solvent 20.
- the transdermal absorption gas is supplied into the sealed container 41 through the delivery tube 23 by the gas pressure of the cylinder 11. Then, the percutaneous absorption gas is heated by the heater 42, whereby the floating droplets contained in the percutaneous absorption gas are evaporated. As a result, a gas for percutaneous absorption that does not contain suspended droplets is obtained. (5) The percutaneous absorption gas that does not contain floating droplets passes through the delivery tube 43 and is used for the next stage.
- the solvent 20 in the tank 21 may be kept at room temperature, but may be heated by providing a heating unit in the tank 2. If the solvent 20 is heated in the tank 21, evaporation of the floating droplets in the sealed container 41 of the floating droplet removing unit 4 occurs efficiently.
- the temperature of the heater 42 of the floating droplet removing unit 4 is preferably near the boiling point of the solvent 20 and more preferably above the boiling point. However, if the temperature of the heater 42 is too high, the gas for percutaneous absorption obtained from the delivery tube 43 becomes too hot and may cause burns to the human body. Therefore, the temperature of the heater 42 is preferably set so that the temperature of the obtained transdermal absorption gas is 25 ° C. to 100 ° C., preferably 50 ° C. or less. When the solvent 20 is water, for example, the temperature of the heater 42 is preferably set to 100 ° C. to 150 ° C. The temperature of the heater 42 is preferably raised in advance.
- the confirmation that floating droplets are generated in the tank 21 is performed by applying a moisture absorbing member such as a filter paper to the outlet end 232 of the delivery tube 23 so that the moisture absorbing member gets wet.
- a moisture absorbing member such as a filter paper
- the tank 21 is a sealed container, almost all of the air in the tank 21 is replaced with carbon dioxide after a certain time. Therefore, it is not necessary to set the concentration of carbon dioxide supplied from the carbon dioxide supply unit 1.
- the suspended droplet removing unit 4 may also serve as a unit for transdermally absorbing gas to animals or humans.
- a part of the sealed container 41 is constituted by an opening / closing cover made of rubber, the opening / closing cover is opened, a desired part such as a human body is put in the sealed container 41, the opening / closing cover is closed, and in this state The apparatus 10A is activated.
- the percutaneous absorption gas that has passed through the floating droplet removing unit 4 may be sprayed directly onto a desired part such as a human body.
- a desired site such as a human body is sealed with a hermetic envelope, and the sealed space is filled with the percutaneous absorption gas that has passed through the floating droplet removing unit 4 as it is, and the desired site is exposed to the percutaneous absorption gas. You may do it.
- the exposure time is preferably 5 minutes or more, more preferably 10 minutes or more per time. However, there is no upper limit on the exposure time.
- the gas for percutaneous absorption that has passed through the floating droplet removing unit 4 does not contain floating droplets, it passes through clothes and the like and is absorbed through the skin, and does not wet clothes and skin.
- the gas for percutaneous absorption may be used for a part of the human body not wearing clothes or the like.
- FIG. 2 is a schematic configuration diagram showing another example of the first percutaneous absorption gas production apparatus of the present invention.
- the apparatus 10B includes a carbon dioxide supply unit 1, a solvent vapor generation unit 2, and a floating droplet removal unit 4.
- the solvent vapor generation unit 2 also serves as a transdermal absorption gas generation unit.
- the floating droplet removing unit 4 includes a cylindrical container 45, sponge bodies 461 and 462 in which both ends of the container 45 are closed, an adsorbent 47 filled in the container 45, and a delivery tube 48. Yes.
- the delivery tube 23 passes through the sponge body 461 and communicates with the container 45.
- the delivery tube 48 passes through the sponge body 462.
- the apparatus 10B having the above-described configuration operates as follows. (1) The carbon dioxide supply unit 1 is operated, and gaseous carbon dioxide is supplied to the air stone 22. (2) From the air stone 22, fine bubbles of carbon dioxide are vigorously released into the solvent 20. Then, the bubbles reach the liquid surface 201 of the solvent 20 and are ruptured, whereby a floating droplet of the solvent 20 is generated in the tank 21. On the other hand, since the solvent 20 is vaporizable, vapor of the solvent 20 is also generated in the tank 21. (3) In the tank 21, carbon dioxide and the vapor of the solvent 20 are mixed, and a transdermal absorption gas containing a carbon dioxide solvent complex formed by combining the two is generated. This percutaneous absorption gas includes the generated suspended droplets.
- the transdermal absorption gas is supplied into the container 45 through the delivery tube 23 by the gas pressure of the cylinder 11. Then, floating droplets contained in the transdermal absorption gas are adsorbed by the adsorbent 47. As a result, a gas for percutaneous absorption that does not contain suspended droplets is obtained. (5) The percutaneous absorption gas containing no suspended droplets passes through the delivery tube 48 and is used for the next stage.
- the adsorbent 47 is a substance that can adsorb floating droplets of the solvent 20 without chemically reacting with carbon dioxide and the solvent 20.
- the adsorbent 47 the adsorbent described above can be used.
- the cylindrical container 45 preferably has a sealed structure, and can adopt any shape such as a circular cross section and a rectangular cross section.
- the floating droplet removing unit 4 may include a heating unit for heating the transdermal absorption gas in the container 45.
- the adsorbent 47 filled in the container 45 has a limit in the amount of floating droplets adsorbed, it is necessary to replace the adsorbent with a new adsorbent as appropriate.
- FIG. 3 is a schematic configuration diagram showing an example of a second percutaneous absorption gas production apparatus of the present invention.
- the apparatus 10C includes a carbon dioxide supply unit 6, a solvent vapor generation unit 7, and a transdermal absorption gas generation unit 8.
- the carbon dioxide supply unit 6 includes a cylinder 61 that stores liquefied carbon dioxide, a regulator 62, and a delivery tube 63.
- the carbon dioxide supply unit 6 depressurizes carbon dioxide from the cylinder 61 by the regulator 62 and supplies the carbon dioxide to the transdermal absorption gas generation unit 8 through the delivery tube 63.
- the solvent vapor generation unit 7 includes a tank 71 that stores the solvent 20, an adjustment unit 72 that adjusts the delivery mode of the solvent 20 from the tank 71, a delivery tube 73, and a planar heater 74 that vaporizes the solvent 20. It is equipped with.
- the percutaneous absorption gas generator 8 includes a sealed container 81 and a delivery tube 82.
- a planar heater 74 is installed on the bottom surface in the container 81, and an outlet end portion 731 of the delivery tube 73 is located above the planar heater 74.
- An outlet end 631 of the delivery tube 63 is also located in the container 81.
- the apparatus 10C having the above-described configuration operates as follows.
- the solvent vapor generation unit 7 operates. That is, the solvent 20 in the tank 71 is dropped onto the planar heater 74 from the outlet end portion 731 of the delivery tube 73.
- the planar heater 74 is raised in advance to a temperature at which the solvent 20 is vaporized.
- the dropping mode of the solvent 20 is adjusted by the adjusting unit 72 so as to be a predetermined amount per unit time at predetermined time intervals. As a result, the dropped solvent 20 is instantly vaporized to become vapor and no floating droplets are generated.
- the temperature of the planar heater 74 is set so that the vapor pressure of the solvent 20 in the container 81 does not exceed the saturated vapor pressure of the solvent 20 at the temperature of the planar heater 74.
- a solvent vapor that does not include floating droplets is generated in the container 81.
- the carbon dioxide supply unit 6 is activated, and gaseous carbon dioxide is supplied into the container 81 through the delivery tube 63. Since the cylinder 61 contains liquefied carbon dioxide, the supplied carbon dioxide does not contain floating droplets.
- carbon dioxide not containing floating droplets and solvent vapor not containing floating droplets are mixed, and a gas for percutaneous absorption containing a carbon dioxide solvent complex formed by combining the two. Is generated. Therefore, the generated gas for percutaneous absorption does not contain suspended droplets.
- the percutaneous absorption gas that does not contain floating droplets passes through the delivery tube 82 and is used for the next stage.
- a heater 83 for gas heating may be provided in the sealed container 81 of the percutaneous absorption gas generation unit 8.
- the temperature of the heater 83 is preferably room temperature or higher, particularly 40 ° C. or higher. However, if the temperature of the heater 83 is too high, the gas for percutaneous absorption obtained from the delivery tube 82 becomes too hot and may cause burns to the human body. Therefore, the temperature of the heater 83 is preferably set so that the temperature of the obtained transdermal absorption gas is 25 ° C. to 100 ° C., preferably 50 ° C. or less. When the solvent 20 is water, for example, the temperature of the heater 83 is preferably set to 100 ° C. to 150 ° C. The temperature of the heater 83 is raised in advance.
- the planar heater 74 for example, a general heater having a heating wire on the back surface of a heat-resistant plate made of metal or ceramic can be used.
- the temperature of the heater 74 is preferably near the boiling point of the solvent 20, and more preferably equal to or higher than the boiling point. However, if the temperature of the heater 74 is too high, the percutaneous absorption gas obtained from the delivery tube 82 becomes too hot and may cause burns such as a human body. Therefore, the temperature of the heater 74 is preferably set so that the temperature of the obtained transdermal absorption gas is 25 ° C. to 100 ° C., preferably 50 ° C. or less. When the solvent 20 is water, for example, the temperature of the heater 74 is preferably set to 100 ° C. to 150 ° C.
- Examples of the dropping mode of the solvent 20 include the following specific examples. That is, when the solvent 20 is water and the heater 74 is a metal plate set at 120 ° C., 1 ml of the solvent 20 is dropped for 2 seconds every 4 cm 2 of the heater 74 at intervals of 1 minute. .
- Carbon dioxide is preferably supplied into the container 81 when the vapor pressure of the solvent 20 in the container 81 becomes 30% or more of the saturated vapor pressure of the solvent 20 at the temperature of the heater 74.
- the vapor pressure of the solvent 20 in the container 81 is preferably as high as possible, but should not exceed the saturated vapor pressure. This is because if the vapor pressure of the solvent 20 in the container 81 exceeds the saturated vapor pressure, floating droplets of the solvent 20 are likely to be generated in the container 81.
- Carbon dioxide is preferably supplied into the container 81 so that the concentration in the container 81 is 15% or more, preferably 30% or more.
- the carbon dioxide concentration in the container 81 is preferably as high as possible, and there is no upper limit.
- the generation of the solvent vapor and the mixing of the solvent vapor and carbon dioxide are performed in one container 81. However, if no floating droplets are generated, they may be performed in separate containers.
- the container 81 may also serve as an administration unit for a gas for transdermal absorption to animals or humans.
- a part of the container 81 is constituted by an opening / closing cover made of rubber, the opening / closing cover is opened, a desired part such as a human body is put in the container 81, the opening / closing cover is closed, and the apparatus 10C is in that state. Is activated.
- Example 1 The present embodiment relates to an example of a first method for producing a gas for percutaneous absorption.
- FIG. 4 is a schematic side sectional view of the manufacturing apparatus used in this embodiment.
- FIG. 5 is a partially omitted plan view of the apparatus of FIG.
- This apparatus 100 ⁇ / b> A includes a carbon dioxide supply unit 1, a solvent vapor generation unit 2, and a floating droplet removal unit 4.
- the solvent vapor generation unit 2 also serves as a transdermal absorption gas generation unit.
- the carbon dioxide supply unit 1 includes a cylinder 11 that contains liquefied carbon dioxide, a regulator 12, and a delivery tube 13.
- the carbon dioxide supply unit 1 decompresses the carbon dioxide from the cylinder 11 by the regulator 12 and supplies the carbon dioxide to the solvent vapor generation unit 2 through the delivery tube 13.
- the delivery tube 13 is a silicon delivery tube having an inner diameter of 5 mm.
- the solvent vapor generation unit 2 includes a tank 21 that stores the solvent 20, an air stone 22 installed in the tank 21, a joint 23A, and a delivery tube 23B.
- the tank 21 is made of polypropylene, has a rectangular parallelepiped shape, and has dimensions of 17 cm in length, 12 cm in width, and 6 cm in height.
- the air stone 22 has a rectangular parallelepiped shape, is fixed to the bottom surface of the tank 21 with an adhesive, and has dimensions of 100 mm in length, 15 mm in width, and 20 mm in height.
- the air stone 22 is connected to the delivery tube 13 penetrating the side wall of the tank 21.
- the joint 23A is fixed to the center of the upper surface of the tank 21, is made of plastic, and has a length of 25 mm and an inner diameter of 2 mm.
- the delivery tube 23B connects the joint 23A and the suspended droplet removal unit 4 and is a silicon delivery tube having an inner diameter of 5 mm.
- the amount of the solvent 20 is set so that the liquid level 201 of the solvent 20 is located above the air stone 22 and below the end of the joint 23A.
- the floating droplet removing unit 4 includes a sealed container 41, a heater 42 installed in the sealed container 41, and a delivery tube 43.
- the delivery tube 23B communicates with the sealed container 41.
- Solvent 20 500 ml of deionized water -Heater 42 temperature: 105 ° C -Carbon dioxide concentration in the container 41 ... 75% -Heating time in the floating droplet removing unit 4 ... 10 minutes
- (Operation) Device 100A operates as follows. (1) The carbon dioxide supply unit 1 is operated, and gaseous carbon dioxide is supplied to the air stone 22. (2) From the air stone 22, fine bubbles of carbon dioxide are vigorously released into the solvent 20. Then, the bubbles reach the liquid surface 201 of the solvent 20 and are ruptured, whereby a floating droplet of the solvent 20 is generated in the tank 21. On the other hand, since the solvent 20 is vaporizable, vapor of the solvent 20 is also generated in the tank 21. (3) In the tank 21, carbon dioxide and the vapor of the solvent 20 are mixed, and a transdermal absorption gas containing a carbon dioxide solvent complex formed by combining the two is generated. This percutaneous absorption gas also includes suspended droplets of the solvent 20.
- the transdermal absorption gas is supplied into the sealed container 41 through the delivery tube 23B by the gas pressure of the cylinder 11. Then, the percutaneous absorption gas is heated by the heater 42, whereby the floating droplets contained in the percutaneous absorption gas are evaporated. As a result, a gas for percutaneous absorption that does not contain suspended droplets is obtained. In the container 41, the temperature was 42 ° C. and the humidity was 90%. (5) The percutaneous absorption gas that does not contain floating droplets passes through the delivery tube 43 and is used for the next stage.
- the mass of the suspended droplet was 0 mg.
- a third measurement value was obtained in the same manner as in (2) above. (4) Then, by subtracting the difference between the third measurement value and the first measurement value from the difference between the second measurement value and the first measurement value, the mass of the suspended droplet adsorbed on the filter paper was obtained. .
- Test conditions A test for determining the effect of the obtained gas for percutaneous absorption was performed as follows. That is, a male subject took off his socks, rolled up his trousers to his knees, sat on a chair, and placed both feet in an open container. Next, a rubber sheet was placed so as to cover both feet and the upper opening of the container, and the container was in a semi-sealed state. And the gas for percutaneous absorption which came through the delivery tube 43 was filled in the container, and the state was maintained for 5 minutes. That is, both legs of a male subject were exposed to a percutaneous absorption gas for 5 minutes.
- the effect was determined by determining the rate of increase or decrease in blood flow in the instep of male subjects.
- the blood flow was measured using a laser Doppler blood flow meter (product name “OMEGAZONE OZ-1” manufactured by Omega Wave). First, the blood flow before the test was measured. Next, after the test, the foot was taken out from the container, and the blood flow after 1 minute and 2 minutes was measured. Table 1 shows the results.
- Comparative Example 1 In Comparative Example 1, the apparatus 100A of Example 1 was used, but the heater 42 was used without being energized. Further, only the following points are different from the first embodiment, and the other points are the same as the first embodiment.
- Example 1 In Example 1, the blood flow after 1 minute increased by 17.5%, and the subject's feet were not wet at all. On the other hand, in Comparative Example 1, the blood flow of the left foot slightly increased, but the blood flow of the right foot slightly decreased. This is considered to be an error in measurement accuracy, and it is considered that there was actually no change in blood flow. From the above, according to the transdermal absorption gas obtained in Example 1, the action of carbon dioxide can be exerted strongly.
- the present embodiment relates to another example of the first method for producing a gas for percutaneous absorption.
- FIG. 6 is a schematic side sectional view of the manufacturing apparatus used in this example.
- the apparatus 100B includes a carbon dioxide supply unit 1, a solvent vapor generation unit 2, and a floating droplet removal unit 4.
- the solvent vapor generation unit 2 also serves as a transdermal absorption gas generation unit.
- the carbon dioxide supply unit 1 and the solvent vapor generation unit 2 are the same as the apparatus 100A.
- the floating droplet removing unit 4 includes a cylindrical container 45, sponge bodies 461 and 462 in which both ends of the container 45 are closed, an adsorbent 47 filled in the container 45, a joint 46A, a joint 48A, and a delivery.
- the delivery tube 23B communicates with the inside of the container 45 through a joint 46A penetrating the center of the sponge body 461.
- the delivery tube 48B is connected to a joint 48A passing through the center of the sponge body 462.
- the cylindrical container 45 is made of plastic, has a circular cross section, and has a length of 15 cm and a diameter of 8 cm.
- the sponge bodies 461 and 462 are synthetic resin foams having dimensions of 1 cm in thickness and 8 cm in diameter.
- Table 2 shows the type and temperature of the solvent 20, the type of the adsorbent 47, the carbon dioxide concentration in the container 45, and the like.
- (Operation) Device 100B operates as follows. (1) The carbon dioxide supply unit 1 is operated, and gaseous carbon dioxide is supplied to the air stone 22. (2) From the air stone 22, fine bubbles of carbon dioxide are vigorously released into the solvent 20. Then, the bubbles reach the liquid surface 201 of the solvent 20 and are ruptured, whereby a floating droplet of the solvent 20 is generated in the tank 21. On the other hand, since the solvent 20 is vaporizable, vapor of the solvent 20 is also generated in the tank 21. (3) In the tank 21, carbon dioxide and the vapor of the solvent 20 are mixed, and a transdermal absorption gas containing a carbon dioxide solvent complex formed by combining the two is generated. This percutaneous absorption gas also includes suspended droplets of the solvent 20.
- the transdermal absorption gas is supplied into the container 45 through the delivery tube 23B by the gas pressure of the cylinder 11.
- the gas pressure is the same as in Example 1.
- floating droplets contained in the transdermal absorption gas are adsorbed by the adsorbent 47.
- a gas for percutaneous absorption that does not contain suspended droplets is obtained.
- the percutaneous absorption gas that does not contain floating droplets passes through the delivery tube 48B and is used for the next stage.
- the gas for percutaneous absorption that had passed through the delivery tube 48B was introduced through a check valve into a plastic bag having a check valve at the bottom.
- the plastic bag has a length of 80 cm and a width of 20 cm.
- a filter paper JIS-P-3801 standard product
- the mass of the suspended droplet was 8 mg in Example 4, 7 mg in Example 7, and 0 mg in the other examples.
- Test condition 1 The male subject's left arm was covered with a plastic bag having a check valve on the bottom.
- the plastic bag has a length of 80 cm and a width of 20 cm.
- the gas for percutaneous absorption that had passed through the delivery tube 48B was introduced into the plastic bag through the check valve.
- the left arm was exposed for a predetermined time. Then, using the laser Doppler blood flow meter described above, the blood flow in the left arm was measured and compared with the blood flow measured before exposure. Table 2 shows the results.
- Test condition 2 The test subject is a 47-year-old woman who has been suffering from cold legs for many years.
- the subject's right leg was placed in a polypropylene bag with a check valve, with stockings attached.
- the bag has dimensions of 80 cm in length and 20 cm in width.
- the mouth of the bag was tied with a cloth belt on the knee of the subject's right leg, and the bag was sealed.
- the gas for percutaneous absorption obtained in Example 2 was injected into the bag through a check valve. The right leg was exposed for only 10 minutes.
- Table 2 shows the type and temperature of the solvent 20, the type of the adsorbent 47, the carbon dioxide concentration in the container 45, and the like.
- Test condition 1 The percutaneous absorption gas that had passed through the delivery tube 23B was introduced into the plastic bag through the check valve. Others were the same as those in Examples 2 to 10. Table 2 shows the results.
- Example 11 This example relates to a second method for producing a gas for percutaneous absorption.
- FIG. 7 is a schematic side sectional view of the manufacturing apparatus used in this example.
- FIG. 8 is a partially omitted plan view of the apparatus of FIG.
- This device 100C includes a carbon dioxide supply unit 6, a solvent vapor generation unit 7, and a transdermal absorption gas generation unit 8.
- the carbon dioxide supply unit 6 includes a cylinder 61 that stores liquefied carbon dioxide, a regulator 62, a delivery tube 63A, and an ejection unit 63B.
- the delivery tube 63A is connected to the ejection part 63B.
- the carbon dioxide supply unit 6 depressurizes the carbon dioxide from the cylinder 61 by the regulator 62 and supplies the carbon dioxide to the transdermal absorption gas generation unit 8 through the delivery tube 63A and the ejection unit 63B.
- the delivery tube 63A is a brass pipe having an inner diameter of 3 mm, and extends through the side wall of the box 81A of the percutaneous absorption gas generation unit 8.
- the ejection part 63B is configured by arranging a brass pipe having an inner diameter of 3 mm in an annular shape so as to surround the planar heater 74 of the solvent vapor generation part 7.
- the ejection part 63B has a square in plan view, and its one side is 17 cm. Further, upward jet outlets 630 having a diameter of 1 mm are formed in the jet part 63B at intervals of 1 cm.
- the solvent vapor generation unit 7 includes a tank 71 that stores the solvent 20, an adjustment unit 72 that adjusts the supply mode of the solvent 20 from the tank 71, a delivery tube 73, and a planar heater 74 that vaporizes the solvent 20. It is equipped with.
- the adjustment unit 72 has an electric valve that can automatically adjust the opening / closing time and the opening / closing interval.
- the planar heater 74 is installed at a depth of 3 cm from the bottom surface in the center of the bottom surface of the box 81A of the percutaneous absorption gas generation unit 8, has a square shape in plan view, and has a dimension of 15 cm on a side. ing.
- the delivery tube 73 is a stainless steel pipe having an inner diameter of 3 mm, extends to the upper center of the planar heater 74, and is bent 90 degrees downward.
- the percutaneous absorption gas generator 8 includes an upper opening box 81A.
- the box 81A is made of stainless steel, has a square shape in plan view, and has dimensions of 40 cm in height and 35 cm on a side.
- the upper opening of the box 81A is covered with a rubber cover.
- a planar heater 83 is provided on the four side walls of the box 81A.
- Solvent 20 Deionized water Surface heater 74 temperature 105 ° C -Supply mode of the solvent 20 from the delivery tube 73 ... 1 ml is intermittently dropped every 30 seconds-Temperature of the planar heater 83 ... 50 ° C -Carbon dioxide concentration in the box 81A ... 75%
- the solvent vapor generation unit 7 operates. That is, the solvent 20 in the tank 71 is dropped onto the planar heater 74 from the outlet end portion 731 of the delivery tube 73.
- the planar heater 74 is raised to 105 ° C. in advance.
- the dropping mode of the solvent 20 is adjusted by the adjusting unit 72 so that 1 ml is dropped intermittently every 30 seconds. As a result, the dropped solvent 20 instantly evaporates into a vapor and no floating droplets are generated.
- the temperature of the planar heater 74 is set so that the vapor pressure of the solvent 20 in the box 81 ⁇ / b> A does not exceed the saturated vapor pressure of the solvent 20 at the temperature of the planar heater 74.
- a solvent vapor that does not contain floating droplets is generated in the box 81A.
- the carbon dioxide supply unit 6 is activated to supply gaseous carbon dioxide into the box 81A. Since the cylinder 61 contains liquefied carbon dioxide, the supplied carbon dioxide does not contain floating droplets.
- Example 6 The apparatus 100C was used, but the solvent 20 was not supplied from the tank 71, and 100 ml of the solvent 20 was placed in the box 81A. Therefore, floating droplets were generated. The rest is the same as Example 11 except the following points.
- Solvent 20 Deionized water Surface heater 74 temperature 105 ° C -Supply mode of the solvent 20 from the delivery tube 73-No water supply-Temperature of the planar heater 83-50 ° C -Carbon dioxide concentration in the box 81A ... 75%
- Example 7 Although apparatus 100C was used, carbon dioxide was not supplied. The rest is the same as Example 11 except the following points.
- Example 11 In Example 11, the average increase rate of blood flow was 42.6% after 1 minute and 37.0% after 2 minutes. Therefore, Example 11 was not only strong in increasing blood flow, but also had good sustainability in increasing blood flow. Also, the subject's feet were not wet at all. In Comparative Example 6, a large amount of floating droplets were generated, a large amount of condensation was observed on the inner wall of the box 81A, the humidity was 95%, and the temperature reached 45 ° C. The subject's feet were wet with steam, and the subject felt unbearable heat but was patient. The average blood flow rate increase rate remained at 24.5% after 1 minute.
- Example 11 can exhibit the effect by percutaneous absorption of a carbon dioxide strongly, and can also exhibit with sufficient sustainability.
- Example 12 The carbon dioxide concentration in the box 81A was set to 30%, and the others were the same as those in Example 11.
- Example 12 In Example 12, the carbon dioxide concentration was only 30%, but the average increase in blood flow was 42.1% after 1 minute and 29.2% after 2 minutes. Therefore, Example 12 can exert the effect by percutaneous absorption of carbon dioxide strongly, and can also exhibit with sufficient sustainability.
- the percutaneous absorption gas production apparatus of the present invention can obtain a percutaneous absorption gas that does not contain suspended droplets of solvent, it has great industrial utility value.
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Abstract
Description
(1)二酸化炭素の経皮吸収による効果を、簡便に且つ顕著に、向上できる。
(2)二酸化炭素が広範囲の皮膚から容易に経皮吸収されるのを、実現できる。
(3)衣服など及び皮膚を濡らすことなく、二酸化炭素が経皮吸収されるのを、実現できる。
(4)二酸化炭素が衣服などで隠れている皮膚からも容易に経皮吸収されるのを、実現できる。
本発明の経皮吸収用気体製造装置は、2種類に大別できる。第1の装置は、生成された経皮吸収用気体から、溶媒の浮遊液滴を除去する、浮遊液滴除去部を、備えている。第2の装置は、生成される経皮吸収用気体に、溶媒の浮遊液滴が混入するのを、防止する、混入防止手段を、含んでいる。
本発明の経皮吸収用気体製造方法は、2種類に大別できる。第1の方法は、生成された経皮吸収用気体から、溶媒の浮遊液滴を除去する、浮遊液滴除去工程を、有している。第2の方法は、生成される経皮吸収用気体に、溶媒の浮遊液滴が混入するのを、防止する、混入防止工程を、含んでいる。
(経皮吸収用気体)
得られた経皮吸収用気体は、二酸化炭素を15容量%以上含有し、溶媒の蒸気圧が飽和蒸気圧の30%以上であればよく、25℃以上の温度を有するのが好ましい。経皮吸収用気体の二酸化炭素含有量は、30容量%以上がより好ましく、50容量%以上が最も好ましい。溶媒の蒸気圧は飽和蒸気圧の50%以上がより好ましく、70%以上が最も好ましい。なお、本発明者は、二酸化炭素の経皮吸収効率は皮膚温が25℃以下の場合に低下する、ということを解明している。
次の(a)、(b)、又は(c)の方法を、採用できる。しかし、これらに限るものではない。
(a)埃などが少ない状態で、微粒子測定器などを用いて観察する。
(b)チンダル現象の有無を肉眼で観察する。浮遊液滴が含まれていない場合、チンダル現象は認められない。具体的には、暗い密閉容器中で、対象物に束状の光を当て、光の通り道の有無を観察する。光の通り道が認められない場合、浮遊液滴はないと判断できる。
(c)紙のような熱伝導率の低い素材でできたシートを、対象物に晒す。浮遊液滴があると、当該シートに浮遊液滴が吸着されてシミができる。なお、金属のような熱伝導率の高い素材でできたシートは、浮遊液滴が無くても、溶媒の蒸気が接触すると、当該蒸気の熱を奪って溶媒を凝結させ、浮遊液滴と同様に、当該シートにシミを作るので、好ましくない。
浮遊液滴を定量する方法としては、浮遊液滴を吸着する熱伝導率の低い素材でできたシート(例えば濾紙)を、対象物に一定時間暴露し、吸着量を測定する、という方法を、採用できる。具体的には、次のとおりである。
(1)まず、濾紙と通気性の無いアルミパウチとの合計質量を測定して、第1測定値を得る。
(2)次に、濾紙を、対象物に一定時間暴露した後、直ちにアルミパウチに入れて密封する。そして、その合計質量を測定して、第2測定値を得る。なお、浮遊液滴である溶媒は気化性であるので、濾紙に吸着された浮遊液滴は、時間経過とともに、濾紙から気化していく。それ故、浮遊液滴の吸着量を正確に測定するためには、濾紙は、曝露後、「直ちに」、アルミパウチに入れて、密封しなければならない。
(3)一方、濾紙は溶媒の蒸気(溶媒が水の場合は水蒸気)も吸着するので、濾紙を、対象物と同じ温度における湿度を有する溶媒の蒸気に、一定時間暴露した後、直ちにアルミパウチに入れて密封する。そして、その合計質量を測定して、第3測定値を得る。
(4)そして、第2測定値と第1測定値との差から、第3測定値と第1測定値との差を、引く。これにより、濾紙に吸着された浮遊液滴の質量が、求められる。
溶媒としては、気体状の二酸化炭素を溶解可能であり、常温で液体であり、気化性を有しているものであれば、特に制限されることなく使用できる。具体的には、無機溶媒又は有機溶媒を使用できる。
二酸化炭素を発生する二酸化炭素源としては、特に制限はなく、液化二酸化炭素、ドライアイスなどを、使用できる。また、例えば、酸と炭酸塩の反応により、二酸化炭素を発生させてもよい。これらの中でも、液化二酸化炭素は、水分などの不純物が少なく、浮遊液滴を殆ど含まないため、好ましい。液化二酸化炭素は、レギュレータを用いて、減圧して使用することが、好ましい。また、レギュレータからは、通常、低温の二酸化炭素ガスが出てくるので、加温して使用することが、好ましい。
吸着剤としては、化学吸着剤と物理吸着剤とを使用できる。化学吸着剤としては、塩化カルシウム、硫酸マグネシウム、五酸化二リン、濃硫酸、又は過塩素酸マグネシウムなどを、使用できる。物理吸着剤としては、ゼオライト、シリカゲル、酸化アルミニウム、活性炭、綿、又はモレキュラーシーブなどを、使用できる。これらの吸着剤は、溶媒が水である場合はもちろん、溶媒がアルコールや油脂である場合でも、同様に使用できる。なお、溶媒の物性に適応した吸着剤を使用するのが好ましい。より具体的には、例えば、溶媒と吸着剤とは、化学反応を起こさない組み合わせとする。
浮遊液滴を含まない二酸化炭素は、次のようにして得ることができる。
(a)液化二酸化炭素を、レギュレータを用いて減圧する。液化二酸化炭素は、水分などを含まない、純度の高い、二酸化炭素であるので、気化したときに浮遊液滴を殆ど含まない。
(b)浮遊液滴を含んでいる二酸化炭素から、浮遊液滴を除去する。この浮遊液滴の除去方法としては、例えば、吸着方法と加熱方法とがある。
例えば、いわゆるドライアイスを使用する場合、ドライアイスから発生する二酸化炭素は、空気中の水蒸気を冷却して凝結させるので、浮遊液滴(白煙)を発生する。そこで、ドライアイスから発生する二酸化炭素を、吸着剤に曝露する。これにより、二酸化炭素に含まれる浮遊液滴が、吸着剤に吸着されて除去される。吸着剤としては、前述のものを使用できる。なお、微生物の発酵などによって発生する二酸化炭素も、ドライアイスの場合と同様に処理して、使用できる。
浮遊液滴を含んでいる二酸化炭素を加熱して、浮遊液滴を蒸発させる。具体的な加熱方法としては、(i)赤外線や遠赤外線などの熱線を、浮遊液滴を含んでいる二酸化炭素に照射する方法、(ii) 浮遊液滴を含んでいる二酸化炭素を、電熱ヒーターなどの高温体に接触させる方法などを、採用できる。なお、加熱方法は、二酸化炭素や溶媒に化学変化を起こす方法でなければ、前述の方法に限定されない。
浮遊液滴を含まない溶媒蒸気は、次のようにして得ることができる。
(a)溶媒を、その温度における飽和蒸気圧以下の蒸気圧となるように、加熱する。加熱源の温度は、溶媒蒸気を効率的に生成するために、溶媒の沸点以上であることが好ましい。加熱源の温度の上限は、溶媒が分解しない温度であることは当然であるが、溶媒の沸点より概ね50℃高い温度まで許容される。溶媒が水である場合には、溶媒を100℃以上150℃以下に加熱するのが好ましい。
浮遊液滴を含んでいない二酸化炭素と浮遊液滴を含んでいない溶媒蒸気との混合は、両者を単に混合させるだけでよい。なお、両者の混合は、密閉容器中で行うのが好ましい。また、混合した後に混合気体の温度が下がると、溶媒蒸気が浮遊液滴を発生するので、両者は、加熱しながら混合するのが好ましい。加熱温度は、溶媒蒸気の温度以上が好ましい。具体的には、加熱温度は、加熱後に得られた経皮吸収用気体の温度が100℃以下になるように、設定するのが好ましく、更には、50℃以下になるように、設定するのがより好ましい。但し、加熱後に得られる経皮吸収用気体の温度は、25℃以上が好ましい。また、混合容器自体の内壁も加熱するのが、好ましい。更には、混合容器の外壁に断熱材を使用することによって、混合気体の温度低下を防ぐのが、好ましい。
(第1製造装置)
図1は、本発明の第1の経皮吸収用気体製造装置の一例を示す模式構成図である。この装置10Aは、二酸化炭素供給部1と、溶媒蒸気生成部2と、浮遊液滴除去部4と、を備えている。溶媒蒸気生成部2は、経皮吸収用気体生成部も兼ねている。
(1)二酸化炭素供給部1が作動して、気体状の二酸化炭素がエアストーン22へ供給される。
(2)エアストーン22からは、二酸化炭素の細かな気泡が溶媒20中へ勢い良く放出される。そして、気泡は、溶媒20の液面201に到達して、破裂し、これにより、タンク21内では、溶媒20の浮遊液滴が生成される。一方、溶媒20は、気化性を有しているので、タンク21内では、溶媒20の蒸気も生成される。
(3)タンク21内では、二酸化炭素と溶媒20の蒸気とが混合され、両者が結合してなる二酸化炭素溶媒複合体を含む経皮吸収用気体が生成される。この経皮吸収用気体には、溶媒20の浮遊液滴も含まれている。
(4)経皮吸収用気体は、ボンベ11のガス圧によって、送出チューブ23を通って密閉容器41内に供給される。そして、経皮吸収用気体は、ヒーター42によって加熱され、これにより、経皮吸収用気体に含まれていた浮遊液滴が蒸発する。この結果、浮遊液滴を含まない経皮吸収用気体が得られる。
(5)浮遊液滴を含まない経皮吸収用気体は、送出チューブ43を通って、次段の用途に供される。
図2は、本発明の第1の経皮吸収用気体製造装置の別の例を示す模式構成図である。この装置10Bは、二酸化炭素供給部1と、溶媒蒸気生成部2と、浮遊液滴除去部4と、を備えている。溶媒蒸気生成部2は、経皮吸収用気体生成部も兼ねている。
(1)二酸化炭素供給部1が作動して、気体状の二酸化炭素がエアストーン22へ供給される。
(2)エアストーン22からは、二酸化炭素の細かな気泡が溶媒20中へ勢い良く放出される。そして、気泡は、溶媒20の液面201に到達して、破裂し、これにより、タンク21内では、溶媒20の浮遊液滴が生成される。一方、溶媒20は、気化性を有しているので、タンク21内では、溶媒20の蒸気も生成される。
(3)タンク21内では、二酸化炭素と溶媒20の蒸気とが混合され、両者が結合してなる二酸化炭素溶媒複合体を含む経皮吸収用気体が生成される。この経皮吸収用気体には、生成された浮遊液滴も含まれている。
(4)経皮吸収用気体は、ボンベ11のガス圧によって、送出チューブ23を通って容器45内に供給される。そして、経皮吸収用気体に含まれる浮遊液滴が、吸着剤47に吸着される。この結果、浮遊液滴を含まない経皮吸収用気体が得られる。
(5)浮遊液滴を含まない経皮吸収用気体は、送出チューブ48を通って、次段の用途に供される。
図3は、本発明の第2の経皮吸収用気体製造装置の一例を示す模式構成図である。この装置10Cは、二酸化炭素供給部6と、溶媒蒸気生成部7と、経皮吸収用気体生成部8と、を備えている。
(1)溶媒蒸気生成部7が作動する。すなわち、タンク71内の溶媒20が、送出チューブ73の出口端部731から、面状ヒーター74上に、滴下される。なお、面状ヒーター74は、溶媒20を気化させる温度に、予め上げておく。溶媒20の滴下態様は、所定時間間隔おきに、単位時間当たり所定量となるように、調節ユニット72によって、調節されている。その結果、滴下された溶媒20は、瞬時に気化されて、蒸気となり、浮遊液滴は発生しない。また、面状ヒーター74の温度は、容器81内の溶媒20の蒸気圧が、面状ヒーター74の温度における溶媒20の飽和蒸気圧を超えないように、設定されている。すなわち、容器81内において、浮遊液滴を含まない溶媒蒸気が生成される。
(2)二酸化炭素供給部6が作動して、気体状の二酸化炭素が送出チューブ63を通って容器81内へ供給される。ボンベ61には、液化二酸化炭素が収容されているので、供給される二酸化炭素は浮遊液滴を含んでいない。
(3)そして、容器81内において、浮遊液滴を含まない二酸化炭素と浮遊液滴を含まない溶媒蒸気とが混合され、両者が結合してなる二酸化炭素溶媒複合体を含む経皮吸収用気体が生成される。それ故、生成された経皮吸収用気体は、浮遊液滴を含んでいない。
(4)浮遊液滴を含まない経皮吸収用気体は、送出チューブ82を通って、次段の用途に供される。
本実施例は、第1の経皮吸収用気体製造方法の一例に関するものである。
図4は、本実施例で用いる製造装置の側面断面略図である。図5は、図4の装置の一部省略平面図である。この装置100Aは、二酸化炭素供給部1と、溶媒蒸気生成部2と、浮遊液滴除去部4と、を備えている。溶媒蒸気生成部2は、経皮吸収用気体生成部も兼ねている。
・溶媒20…脱イオン水500ml
・ヒーター42の温度…105℃
・容器41内の二酸化炭素濃度…75%
・浮遊液滴除去部4における加熱時間…10分間
装置100Aは、次のように作動する。
(1)二酸化炭素供給部1が作動して、気体状の二酸化炭素がエアストーン22へ供給される。
(2)エアストーン22からは、二酸化炭素の細かな気泡が溶媒20中へ勢い良く放出される。そして、気泡は、溶媒20の液面201に到達して、破裂し、これにより、タンク21内では、溶媒20の浮遊液滴が生成される。一方、溶媒20は、気化性を有しているので、タンク21内では、溶媒20の蒸気も生成される。
(3)タンク21内では、二酸化炭素と溶媒20の蒸気とが混合され、両者が結合してなる二酸化炭素溶媒複合体を含む経皮吸収用気体が生成される。この経皮吸収用気体には、溶媒20の浮遊液滴も含まれている。
(4)経皮吸収用気体は、ボンベ11のガス圧によって、送出チューブ23Bを通って密閉容器41内に供給される。そして、経皮吸収用気体は、ヒーター42によって加熱され、これにより、経皮吸収用気体に含まれている浮遊液滴が蒸発する。この結果、浮遊液滴を含まない経皮吸収用気体が得られる。なお、容器41内において、温度は42℃であり、湿度は90%であった。
(5)浮遊液滴を含まない経皮吸収用気体は、送出チューブ43を通って、次段の用途に供される。
容器41内を懐中電灯で照らしたが、チンダル現象は見られなかった。よって、浮遊液滴は存在していなかった。
次の方法で測定したところ、浮遊液滴の質量は0mgであった。
(1)まず、直径90mmの濾紙(JIS-P-3801規格品)と非通気性の密閉式アルミパウチ(縦11cm、横11cm)との合計質量を測定して、第1測定値を得た。
(2)次に、濾紙を、ピンセットで摘んで、容器41内に30秒間晒した後、直ちに、容器41内でアルミパウチに収納し、完全に密封した。そして、その合計質量を測定して、第2測定値を得た。
(3)一方、容器41内の温度及び湿度と同じ条件下で、前記(2)と同様にして、第3測定値を得た。
(4)そして、第2測定値と第1測定値との差から、第3測定値と第1測定値との差を、引くことにより、濾紙に吸着された浮遊液滴の質量を求めた。
得られた経皮吸収用気体の効果を求める試験は、次のように行った。すなわち、男性被験者が、靴下を脱ぎ、ズボンを膝までまくり上げ、椅子に腰掛けて、両足を上開きの容器内に入れた。次に、両足及び容器の上開口を覆うようにゴムシートを載せて、容器を半密閉状態とした。そして、送出チューブ43を通って来た経皮吸収用気体を、容器内に充満させて、5分間、その状態を維持した。すなわち、男性被験者の両足を経皮吸収用気体に5分間曝露した。
男性被験者の足の甲の血流量の増減率を求めることにより、効果を判定した。血流量の測定は、レーザードップラー血流計(製品名「OMEGAZONE OZ-1」オメガウェーブ社製)を用いて行った。まず、試験前の血流量を測定した。次に、試験後、容器から足を出して、1分後及び2分後の血流量を測定した。表1は、その結果を示している。
比較例1は、実施例1の装置100Aを用いたが、ヒーター42に通電せずに用いた。また、下記の点のみ、実施例1とは異なっており、その他は、実施例1と同じである。
容器41内において、送出チューブ23Bから大粒の液滴がシャワーのように噴出し、容器41の底部に短時間で落下し、底部を濡らした。
直径90mmの濾紙(JIS-P-3801規格品)を、ピンセットで摘んで、送出チューブ23Bの先10cmの距離に、30秒間晒した。浮遊液滴の質量は41mgであった。
試験後の血流量の測定は、1分後のみ行なった。表1は、その結果を示している。
実施例1では、1分後の血流量が17.5%増加し、被験者の足は全く濡れなかった。これに対して、比較例1では、左足の血流量が若干増えたが、右足の血流量は僅かに減少した。これは、測定精度の誤差と考えられ、実際には、血流量の変化はなかったと考えられる。
以上から、実施例1で得られた経皮吸収用気体によれば、二酸化炭素の作用を強く発揮できる。
本実施例は、第1の経皮吸収用気体製造方法の別の例に関するものである。
図6は、本実施例で用いる製造装置の側面断面略図である。この装置100Bは、二酸化炭素供給部1と、溶媒蒸気生成部2と、浮遊液滴除去部4と、を備えている。溶媒蒸気生成部2は、経皮吸収用気体生成部も兼ねている。
溶媒20の種類及び温度、吸着剤47の種類、及び、容器45内の二酸化炭素濃度などは、表2に示すとおりである。
装置100Bは、次のように作動する。
(1)二酸化炭素供給部1が作動して、気体状の二酸化炭素がエアストーン22へ供給される。
(2)エアストーン22からは、二酸化炭素の細かな気泡が溶媒20中へ勢い良く放出される。そして、気泡は、溶媒20の液面201に到達して、破裂し、これにより、タンク21内では、溶媒20の浮遊液滴が生成される。一方、溶媒20は、気化性を有しているので、タンク21内では、溶媒20の蒸気も生成される。
(3)タンク21内では、二酸化炭素と溶媒20の蒸気とが混合され、両者が結合してなる二酸化炭素溶媒複合体を含む経皮吸収用気体が生成される。この経皮吸収用気体には、溶媒20の浮遊液滴も含まれている。
(4)経皮吸収用気体は、ボンベ11のガス圧によって、送出チューブ23Bを通って容器45内に供給される。なお、ガス圧は、実施例1と同じである。そして、経皮吸収用気体に含まれる浮遊液滴が、吸着剤47に吸着される。この結果、浮遊液滴を含まない経皮吸収用気体が得られる。
(5)浮遊液滴を含まない経皮吸収用気体は、送出チューブ48Bを通って、次段の用途に供される。
送出チューブ48Bを通って来た経皮吸収用気体を、底に逆止弁を有するビニール袋に、逆止弁を通して導入した。ビニール袋は、長さ80cm、幅20cmの寸法を有している。そして、直径90mmの濾紙(JIS-P-3801規格品)を、ピンセットで摘んで、ビニール袋内の底部で、30秒間晒した。浮遊液滴の質量は、実施例4では8mgであり、実施例7では7mgであり、その他の実施例では0mgであった。
男性被験者の左腕に、底に逆止弁を有するビニール袋を被せた。ビニール袋は、長さ80cm、幅20cmの寸法を有している。次に、送出チューブ48Bを通って来た経皮吸収用気体を、逆止弁を通して、ビニール袋内に導入した。そして、所定時間だけ、左腕を暴露した。その後、前述のレーザードップラー血流計を用いて、左腕の血流量を測定し、曝露前に測定した血流量と比較した。表2は、その結果を示している。
被験者は、長年、脚の冷えに悩んでいる47歳の女性である。逆止弁を有するポリプロピレン製の袋に、被験者の右脚を、ストッキングを付けたままで入れた。なお、袋は、長さ80cm、幅20cmの寸法を有している。次に、被験者の右脚の膝の上で、袋の口を布ベルトで縛り、袋を密閉した。次に、実施例2で得られた経皮吸収用気体を、逆止弁を通して、袋内に注入した。そして、10分間だけ、右脚を暴露した。
本比較例は、装置100Bに比して浮遊液滴除去部4を備えていない装置を、用いた。また、下記の点のみ、実施例2~10とは異なっており、その他は、実施例2~10と同じである。
溶媒20の種類及び温度、吸着剤47の種類、及び、容器45内の二酸化炭素濃度などは、表2に示すとおりである。
実施例2~10と同様にして測定した。浮遊液滴の質量は、比較例2では42mgであり、比較例3では46mgであった。
送出チューブ23Bを通って来た経皮吸収用気体を、逆止弁を通して、ビニール袋内に導入した。その他は、実施例2~10の場合と同様にした。表2は、その結果を示している。
本実施例は、第2の経皮吸収用気体製造方法に関するものである。
図7は、本実施例で用いる製造装置の側面断面略図である。図8は、図7の装置の一部省略平面図である。この装置100Cは、二酸化炭素供給部6と、溶媒蒸気生成部7と、経皮吸収用気体生成部8と、を備えている。
・溶媒20…脱イオン水
・面状ヒーター74の温度…105℃
・送出チューブ73からの溶媒20の供給態様…30秒毎に1mlを断続的に滴下
・面状ヒーター83の温度…50℃
・箱体81A内の二酸化炭素濃度…75%
装置100Cは、次のように作動する。
(1)溶媒蒸気生成部7が作動する。すなわち、タンク71内の溶媒20が、送出チューブ73の出口端部731から、面状ヒーター74上に、滴下される。なお、面状ヒーター74は、105℃に、予め上げておく。溶媒20の滴下態様は、30秒毎に1mlが断続的に滴下されるように、調節ユニット72によって、調節されている。その結果、滴下された溶媒20は、瞬時に蒸発して、蒸気となり、浮遊液滴は発生しない。また、面状ヒーター74の温度は、箱体81A内の溶媒20の蒸気圧が、面状ヒーター74の温度における溶媒20の飽和蒸気圧を超えないように、設定されている。すなわち、箱体81A内において、浮遊液滴を含まない溶媒蒸気が生成される。
(2)二酸化炭素供給部6が作動して、気体状の二酸化炭素が箱体81A内へ供給される。ボンベ61には、液化二酸化炭素が収容されているので、供給される二酸化炭素は浮遊液滴を含んでいない。
(3)そして、箱体81A内において、浮遊液滴を含まない二酸化炭素と浮遊液滴を含まない溶媒蒸気とが混合され、両者が結合してなる二酸化炭素溶媒複合体を含む経皮吸収用気体が生成される。それ故、生成された経皮吸収用気体は、浮遊液滴を含んでいない。
濾紙を、ピンセットで摘んで、経皮吸収用気体生成部8内に30秒間晒し、実施例1と同様に測定したところ、浮遊液滴の質量は0mgであった。
実施例1と同じである。
実施例1と同じである。
装置100Cを用いたが、タンク71からは溶媒20を供給せず、箱体81A内に溶媒20を100ml入れておいた。したがって、浮遊液滴を発生させた。その他は、下記の点を除き、実施例11と同じである。
・溶媒20…脱イオン水
・面状ヒーター74の温度…105℃
・送出チューブ73からの溶媒20の供給態様…給水せず
・面状ヒーター83の温度…50℃
・箱体81A内の二酸化炭素濃度…75%
箱体81A内に多量の白い霧状の浮遊液滴が認められた。
実施例1の方法で測定したところ、浮遊液滴の質量は33mgであった。
実施例1と同じである。
実施例1と同じである。
装置100Cを用いたが、二酸化炭素を供給しなかった。その他は、下記の点を除き、実施例11と同じである。
・面状ヒーター74の温度…105℃
・送出チューブ73からの溶媒20の供給態様…30秒毎に1mlを断続的に滴下
・面状ヒーター83の温度…50℃
・箱体81A内の二酸化炭素濃度…0%
箱体81A内を懐中電灯で照らしたが、チンダル現象は見られなかった。
実施例1の方法で測定したところ、浮遊液滴の質量は0mgであった。
実施例1と同じである。
実施例1と同じである。
実施例11及び比較例6、7の結果を表3に示す。
・実施例11において、血流量平均増加率は、1分後では42.6%、2分後では37.0%であった。したがって、実施例11は、血流量増加作用が強いだけでなく、血流量増加作用の持続性も良好であった。また、被験者の足は全く濡れなかった。
・比較例6では、大量の浮遊液滴が発生し、箱体81Aの内壁などに多量の結露が認められ、湿度は95%となり、温度は45℃に達した。被験者の足は、湯気で全体が濡れ、被験者は、耐えがたい熱さを感じたが、我慢した。血流量平均増加率は、1分後では24.5%に留まった。また、2分後では-1.6%を示したが、これは、高温の浮遊液滴による皮膚温の急上昇のリバウンド現象と推測された。
・比較例7では、加熱水蒸気のみが発生し、浮遊液滴は発生しなかった。箱体81A内の温度は38℃に上昇した。その結果、血流量平均増加率は、1分後では36.8%であったが、2分後では19.2%に留まった。被験者の足は全く濡れなかった。
・以上の結果から、実施例11は、二酸化炭素の経皮吸収による効果を強く発揮でき、更には、持続性良く発揮できる。
箱体81A内の二酸化炭素濃度を30%とし、その他は実施例11と同じとした。
箱体81A内を懐中電灯で照らしたが、チンダル現象は見られなかった。
実施例1の方法で測定したところ、浮遊液滴の質量は0mgであった。
実施例12の結果を表4に示す。
実施例12において、二酸化炭素濃度は30%に過ぎなかったが、血流量平均増加率は、1分後では42.1%、2分後では29.2%であった。したがって、実施例12は、二酸化炭素の経皮吸収による効果を強く発揮でき、更には、持続性良く発揮できる。
Claims (22)
- 気体状の二酸化炭素溶媒複合体を含む、経皮吸収用気体を、製造する装置であって、
気体状の二酸化炭素を供給する二酸化炭素供給部と、
前記二酸化炭素を溶解可能な且つ気化性の、溶媒の、蒸気を生成する、溶媒蒸気生成部と、
供給された前記二酸化炭素と生成された前記溶媒蒸気とを混合して、気体状の前記二酸化炭素溶媒複合体を含む経皮吸収用気体を生成する、経皮吸収用気体生成部と、
を備えており、
(1)生成された前記経皮吸収用気体から、前記溶媒の浮遊液滴を除去する、浮遊液滴除去部を、更に備えており、
又は、
(2)生成される前記経皮吸収用気体に、前記溶媒の浮遊液滴が混入するのを、防止する、混入防止手段を、含んでいる、
ことを特徴とする経皮吸収用気体製造装置。 - 前記浮遊液滴除去部が、前記経皮吸収用気体に含まれている前記浮遊液滴を、蒸発させる、加熱手段を、有している、
請求項1記載の経皮吸収用気体製造装置。 - 前記浮遊液滴除去部が、前記経皮吸収用気体に含まれている前記浮遊液滴を、吸着する、吸着手段を、有している、
請求項1記載の経皮吸収用気体製造装置。 - 前記吸着手段が、化学吸着剤又は物理吸着剤である、
請求項3記載の経皮吸収用気体製造装置。 - 前記混入防止手段が、前記浮遊液滴を含まない前記二酸化炭素を供給するよう構成された、前記二酸化炭素供給部、及び、前記浮遊液滴を含まない前記溶媒蒸気を生成するよう構成された、前記溶媒蒸気生成部、である、
請求項1記載の経皮吸収用気体製造装置。 - 前記二酸化炭素供給部が、液化二酸化炭素を気化して供給するよう構成されている、
請求項5記載の経皮吸収用気体製造装置。 - 前記二酸化炭素供給部が、前記二酸化炭素に含まれている前記浮遊液滴を、蒸発させる、加熱手段を、有している、
請求項5記載の経皮吸収用気体製造装置。 - 前記二酸化炭素供給部が、前記二酸化炭素に含まれている前記浮遊液滴を、吸着する、吸着手段を、有している、
請求項5記載の経皮吸収用気体製造装置。 - 前記溶媒蒸気生成部が、前記溶媒を、その温度における飽和蒸気圧以下の蒸気圧となるように加熱する、加熱手段を、有している、
請求項5記載の経皮吸収用気体製造装置。 - 前記溶媒蒸気生成部が、前記溶媒蒸気に含まれている前記浮遊液滴を、吸着する、吸着手段を、有している、
請求項5記載の経皮吸収用気体製造装置。 - 気体状の二酸化炭素溶媒複合体を含む、経皮吸収用気体を、製造する方法であって、
気体状の二酸化炭素を供給する二酸化炭素供給工程と、
前記二酸化炭素を溶解可能な且つ気化性の、溶媒の、蒸気を、生成する、溶媒蒸気生成工程と、
供給された前記二酸化炭素と生成された前記溶媒蒸気とを混合して気体状の前記二酸化炭素溶媒複合体を含む経皮吸収用気体を生成する、経皮吸収用気体生成工程と、
を有しており、
(1)生成された前記経皮吸収用気体から、前記溶媒の浮遊液滴を除去する、浮遊液滴除去工程を、更に有しており、
又は、
(2)生成される前記経皮吸収用気体に、前記溶媒の浮遊液滴が混入するのを、防止する、混入防止工程を、含んでいる、
ことを特徴とする経皮吸収用気体製造方法。 - 前記浮遊液滴除去工程が、前記経皮吸収用気体に含まれている前記浮遊液滴を、蒸発させる、加熱工程を、有している、
請求項11記載の経皮吸収用気体製造方法。 - 前記浮遊液滴除去工程が、前記経皮吸収用気体に含まれている前記浮遊液滴を、吸着する、吸着工程を、有している、
請求項11記載の経皮吸収用気体製造方法。 - 前記吸着工程が、化学吸着剤又は物理吸着剤を用いて実施される、
請求項13記載の経皮吸収用気体製造方法。 - 前記混入防止工程が、前記浮遊液滴を含まない二酸化炭素を供給する、前記二酸化炭素供給工程、及び、前記浮遊液滴を含まない前記溶媒蒸気を生成する、前記溶媒蒸気生成工程、である、
請求項11記載の経皮吸収用気体製造方法。 - 前記二酸化炭素供給工程が、液化二酸化炭素を供給する、
請求項15記載の経皮吸収用気体製造方法。 - 前記二酸化炭素供給工程が、前記二酸化炭素に含まれている前記浮遊液滴を、蒸発させる、加熱工程を、有している、
請求項15記載の経皮吸収用気体製造方法。 - 前記二酸化炭素供給工程が、前記二酸化炭素に含まれている前記浮遊液滴を、吸着する、吸着工程を、有している、
請求項15記載の経皮吸収用気体製造方法。 - 前記溶媒蒸気生成工程が、前記溶媒を、その温度における飽和蒸気圧以下の蒸気圧となるように加熱する、加熱工程を、有している、
請求項15記載の経皮吸収用気体製造方法。 - 前記溶媒蒸気生成工程が、前記溶媒蒸気に含まれている浮遊液滴を、吸着する、吸着工程を、有している、
請求項15記載の経皮吸収用気体製造方法。 - 請求項1乃至10のいずれか一つの経皮吸収用気体製造装置を用いて得られた、
ことを特徴とする経皮吸収用気体。 - 請求項11乃至20のいずれか一つの経皮吸収用気体製造方法によって得られた、
ことを特徴とする経皮吸収用気体。
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CN104661631A (zh) | 2015-05-27 |
JP6523165B2 (ja) | 2019-05-29 |
KR20160026619A (ko) | 2016-03-09 |
US20160151411A1 (en) | 2016-06-02 |
RU2015150680A (ru) | 2017-08-09 |
JPWO2015001964A1 (ja) | 2017-02-23 |
EP3017803A4 (en) | 2017-05-10 |
EP3017803A1 (en) | 2016-05-11 |
TW201536270A (zh) | 2015-10-01 |
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