JP2010202609A - Sheet for pasting to body contained in container - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a drug formulation which can be manufactured in simple way and at a low cost, and which can continuously feed a gas which has physiological activity to a body in a sufficient quantity to the skin. <P>SOLUTION: The sheet for body pasting contained in a container comprises: sealing a sheet of a laminate of a foaming gel layer or a foaming liquid layer containing a gas bubble with 5-50% of a bubble ratio, and a resin film in a hardly gas-permeable container; and containing at least 30 mass% of a gas which has the physiological activity to a body in a gap part in the container at the time of preservation. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a foam sheet for supplying a gas having physiological activity to the body by applying it to the skin.

  Gases such as oxygen and carbon dioxide are known to have various physiological actions as active ingredients. For example, oxygen is known to have physiological effects such as antibacterial action, wound healing, skin keratinocyte proliferation, collagen production, and carbon dioxide has blood circulation promoting effects. As a form for supplying these to the skin as an active ingredient, there are methods such as dissolving and dispersing in the preparation as an application agent, and sticking as a sheet agent, and they are properly used depending on the purpose. Since the sheet agent can be kept in the pasted state, the active ingredient can be easily and continuously supplied to the skin. However, it is difficult to maintain a high concentration of gas. For example, two dry reagents dissolved or dispersed in the preparation are held in the flexible porous layer to generate oxygen during use. Film (Patent Document 1), oxygen bandage (Patent Document 2) for supplying the skin with a high level of oxygen in advance between layers, hydrogen peroxide and / or oxygen is hydrophobized and hydrophobized A technique (Patent Document 3) released from a powdery mixture containing silicon dioxide has been reported. However, the active ingredient concentration supplied to the skin in a gaseous state by the sheet-like material such as a film or a bandage is almost the same as the concentration supplied from normal air, and a sufficient effect cannot be obtained.

  In addition, a technique for supplying carbon dioxide to the skin for the purpose of obtaining a blood circulation promoting effect is also known. For example, Patent Document 4 discloses a sol-gel transition composition in which a sol in which a high concentration of carbon dioxide is dissolved is used after being applied to a sheet material as a means for containing a high concentration of free carbonic acid. The carbon dioxide percutaneous absorption composition is described, but there is no specific means for preventing the volatilization of carbon dioxide at the time of manufacturing the sheet, and it is difficult to actually supply carbon dioxide to the skin sufficiently. it is conceivable that. Furthermore, in order to improve the sustainability of carbon dioxide, the pH of the liquid or gel is adjusted to 3.5 to 6.5, the carbon dioxide concentration in the liquid or gel is within a certain range, and the volume in the packaging pillow A sheet-like patch having a gel filling ratio of 40% or less is described (Patent Document 5).

Japanese translation of PCT publication No. 8-510155 Special table 2007-524447 Special table 2007-504089 gazette JP 2003-34612 A JP 2005-170937 A

However, these technologies do not take into account the amount of active ingredients supplied to the skin from the formulation when applied to the skin, and are not sufficiently usable due to the adhesiveness and weight of the sheet. There is a demand for a technology that can continuously supply the skin to the skin.
Accordingly, an object of the present invention is to provide a preparation that can be easily and inexpensively manufactured and can continuously supply a sufficient amount of a physiologically active gas to the skin.

Therefore, the present inventor has studied that gas is contained in a liquid or gel sheet as a means for continuously supplying gas to the skin. However, it is difficult to dissolve or disperse a gas component in an amount sufficient to supply the skin sufficiently in the sheet. Many of the sheet agents are mainly aqueous solutions or aqueous gel agents, and bioactive gases with low solubility such as oxygen have a small amount of retention in the sheet agent, resulting in insufficient sustainability during use. As it turns out, the oxygen supply to the skin is not enough.
Therefore, when further examination was made, when a resin film was laminated on a foamed gel layer or foamed liquid layer holding bubbles to form a sheet, and this was sealed in a gas-impermeable container, the oxygen concentration in the voids in the container was set. Reached to control. As a result, when the bubble is replaced with a gas that is physiologically active for the body in the container, and the physiologically active gas is dissolved in the foamed gel layer or the foamed liquid layer, taken out of the container and applied to the skin In addition, the present inventors have found that not only the physiologically active gas in the sheet is efficiently supplied to the skin, but also the effect of the sheet is sustained because the sheet is light and the fit property is improved because it contains bubbles.

  That is, the present invention comprises a foamed gel layer or foamed liquid layer containing bubbles having a cell ratio of 5 to 50%, and a laminated sheet of a resin film sealed in a gas-impermeable container, It is intended to provide a container-attached sheet for body sticking containing 30% by mass or more of a gas having physiological activity with respect to the body in the void, and a method for producing the same.

  The sheet for body sticking of the present invention can be manufactured by a simple operation using an inexpensive material, and a high-concentration physiologically active gas can be continuously applied to the sticking site simply by removing it from the container and sticking it to the body. Can be supplied to. Therefore, physiologically active actions of various gases can be obtained in a safe and simple operation in the skin region. Furthermore, since the skin application surface contains air bubbles, the fit at the time of application is good.

An example of the shape of this invention sheet | seat is shown.

  In the body sticking sheet of the present invention, a foamed gel layer or foamed liquid layer having a bubble rate of 5 to 50% and a laminated sheet of a resin film are sealed in a gas-impermeable container.

The gas-impermeable container that seals the laminated sheet does not allow the gas inside the container to flow out, and can prevent the moisture and other volatile components inside the container from flowing out. It is gas permeable from the point of preventing inflow. Here, “impermeable” means that the gas permeability is 50 cc / m ² · day · atm (ASTM D-1434) or less, preferably non-permeable. Preferable materials are those having heat-sealing properties, specifically, a laminate film laminated with an aluminum foil, a laminate film having an aluminum deposited layer, a polyvinylidene chloride film, a laminate film containing a polyvinylidene chloride layer, and the like. It is done. The container is preferably a flat bag or a gusset.

  The laminated sheet is obtained by laminating a foamed gel layer or foamed liquid layer containing bubbles having a cell rate of 5 to 50% and a resin film. The foamed gel layer or foamed liquid layer is a sheet-like foamed gel layer or foamed liquid layer. The thickness of the laminated sheet is preferably 0.1 to 5 mm from the viewpoint of the amount of physiologically active gas retained and the feeling of use at the time of sticking, and further 0.3 to 4 mm, particularly 0.5 from the viewpoint of fit. ~ 3 mm is preferred.

The foamed gel layer or the foamed liquid layer contains bubbles, and the bubble ratio is 5 to 50% from the viewpoint of the displaceability with the bioactive gas filled in the container and the feeling of use at the time of application. 45%, particularly 10 to 40% is preferred. The size of the bubble depends on the type of gas and the thickness of the sheet, but is in the range of 0.01 to 2 mm in terms of gas retention, sheet strength and flexibility, and feeling of use such as fit and followability. It is preferably 0.01 to 1.5 mm, more preferably 0.01 to 1 mm. Such bubbles can be formed by stirring during formation of the gel layer or liquid layer, generating a gas (gas) by a chemical reaction, or injecting a liquid containing a liquefied gas from a high pressure state. In particular, from the viewpoint of the stability of the bubbles, a foamed gel layer in which bubbles are formed by stirring when forming the gel layer or the liquid layer is preferable. Here, the bubble ratio can be measured as follows.
If the foamed layer is liquid, it is filled in a container of known capacity (AmL) so as not to crush the foam, the weight of the content is measured (Bg), and the calculation is performed according to the equation (1). If the foam layer is gel, cut into a rectangular parallelepiped shape, calculate the volume from the length, width and height (AmL), measure the weight (Bg), and similarly formula (1) Calculate according to It is assumed that the specific gravity of the portion excluding the bubbles is 1.

(Equation 1)
Bubble ratio (%) = (A−B) / A × 100 Formula (1)

  The bubble size can be measured by microscopic observation.

  The foamed gel layer or foamed liquid layer may be in any form of foamed aqueous solution, foamed aqueous gel, foamed emulsion or foamed emulsified gel-like composition containing an oil phase, foamed oil layer, and oily foamed gel. Here, the oil component that forms the oil phase or oil layer includes long chain hydrocarbons, higher fatty acids, higher fatty acid esters, higher fatty acids from the viewpoint of improving the amount of bioactive gas dissolved, safety to the skin, and moisturizing feeling after use. Alcohols, silicones, fluorocarbons and the like can be mentioned. The long-chain hydrocarbon is preferably liquid (25 ° C.), and examples thereof include liquid paraffin, squalane, squalene and the like, and liquid paraffin is particularly preferable. In addition, higher fatty acids, higher fatty acid esters, and higher alcohols are particularly preferred because branched fatty acids, unsaturated fatty acids, branched fatty acid esters, unsaturated fatty acid esters, branched fatty alcohols, unsaturated aliphatic alcohols are liquid, for example, Preferred are natural fats and oils such as jojoba oil, olive oil, castor oil, mink oil and macadamian nut oil, and unsaturated fatty acids such as isopropyl myristate and diglyceryl diisostearate, and esters of branched fatty acids. As silicones, alkyl-modified silicone such as dimethylstearyl polysiloxane, highly polymerized methyl polysiloxane, cross-linked methyl polysiloxane, fluorinated fluorosilicone, and the like are preferable. Furthermore, as fluorocarbons, perfluoropolyethers such as 2- (perfluorohexyl) ethyl 1,3-dimethylbutyl ether, hydrofluoroethers, and the like can be used. These oil components are preferably present in the foamed gel layer or the foamed liquid layer in a state where an oil phase or an oil layer is formed, and 0.1 to 35% by mass in the foamed gel layer or the foamed liquid layer, and further 0.5 to It is preferable to make it contain 20 mass%, especially 0.5-15 mass%.

  Moreover, various emulsifiers can be blended in the foamed gel layer or the foamed liquid layer in order to improve foamability, disperse the oil and plant extract, and improve adhesion to the skin. Nonionic interfaces such as glycerin monofatty acid ester, polyglycerin monofatty acid ester, sorbitan monofatty acid ester, polyethylene glycol monofatty acid ester, polyoxyethylene sorbitan monofatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether Activating agents; anionic surfactants such as linear or branched fatty acid salts having 12 to 18 carbon atoms, alkyl phosphoric acid ester salts having 12 to 18 carbon atoms, N-acyl amino acid salts; stearyltrimethylammonium chloride, distearyldimethyl chloride Mention may be made of cationic surfactants such as ammonium.

  A plant extract can be mix | blended with a foaming gel layer or a foaming liquid layer. Plant extracts include, for example, licorice extract, glycyrrhizic acid and its derivatives, glycyrrhetinic acid and its derivatives, fat-soluble glycyrrhetinic acids, azulene, guaiazulene, oxon extract, chamomile extract, white birch extract, zebra oyster extract, peach leaf extract, yarrow Anti-inflammatory effects such as extract, kyoto extract, loquat leaf extract, body sage extract, eucalyptus extract; What is possessed; Rutin derivatives, Hibamata extract, sage extract, and the like, which are effective for ablation and swelling. Antibiotics other than plant extracts, antifungal agents, anti-inflammatory agents, blood circulation promoters, vitamins, humectants, and the like can also be added. Furthermore, mineral powders such as kaolin, sukumite, zinc oxide, titanium oxide and the like can be blended.

  In forming the foamed gel layer, a water-soluble polymer, a polyhydric alcohol, or the like can be used. Examples of water-soluble polymers include polyacrylic acids, polymethacrylic acids, polyacrylamide, polyvinyl alcohol, polyvinyl pyrrolidone, alginates, gels composed of polyvalent cations such as pectin and the like; carboxymethyl cellulose and the like Examples thereof include cellulose, cellulose derivatives or salts thereof, xanthan gum, gelatin, pullulan, agar, gum arabic, chitosan and water-containing gels using water, such as chitosan and derivatives thereof. Of these, a foamed aqueous gel layer formed of an anionic polymer and a polyvalent cation is preferred. These water-soluble polymers can be used singly or in combination of 0.5 to 30% by weight, more preferably 0.5 to 20% by weight, particularly 0.5 to 15% by weight in the foamed gel layer. Is preferred. Examples of the polyvalent cation include polyvalent metal ions such as aluminum ions.

  Examples of the polyhydric alcohol include glycerin, polyglycerin, propylene glycol, polyethylene glycol, 1,3-butanediol, sorbitol, and xylitol. These polyhydric alcohols can be used singly or in combination of 3 to 60% by mass, more preferably 3 to 50% by mass, and particularly preferably 5 to 40% by mass in the gel. In addition to these polyols, petrolatum, dextrin and the like can also be used for the purpose of adjusting adhesion.

  As the foaming liquid layer, for example, a nonwoven fabric impregnated with an aqueous solution and foamed can be used.

A resin film is laminated on the foamed gel layer or the foamed liquid layer. By laminating the resin film, moisture evaporation from the foamed gel layer or the foamed liquid layer at the time of body sticking can be suppressed and the sheet can be prevented from drying. Further, by putting the laminated sheet into a container, and then filling the container with a bioactive gas and sealing the container, the bioactive gas filled in the container is replaced with bubbles in the foamed gel layer or the foamed liquid layer, And while melt | dissolving directly, bioactive gas permeate | transmits also from the resin film side, and melt | dissolves gradually in a foaming gel layer or a foaming liquid layer. On the other hand, by removing the sheet from the container and sticking the opposite side of the resin film, that is, the foamed gel layer or the foamed liquid layer side to the body, the outflow of the bioactive gas from the film side is suppressed. Physiologically active gas supply amount and duration are improved. From this viewpoint, the gas permeability of the resin film needs to be low, preferably 20000 cc / m ² · day · atm (25 ° C) or less, and more preferably 15000 cc / m ² · day · atm (25 ° C) or less. 0.001 to 13000 cc / m ² · day · atm (25 ° C.) is particularly preferable. Furthermore, when the foamed gel layer or the foamed liquid layer is thick, the physiologically active gas is dissolved from the outer peripheral edge of the sheet, so that it does not have to be substantially oxygen permeable. In addition, the gas permeability of a resin film is the value measured based on ASTM D-1434.

  Examples of the physiologically active gas (gas having physiological activity for the body) include oxygen, carbon dioxide, hydrogen, nitrous oxide, carbon monoxide, and the like, and oxygen and carbon dioxide are preferable.

Examples of the film material include polyethylene (PE), polypropylene (PP), soft vinyl chloride, polyester, nylon, polyurethane, ethylene / vinyl alcohol copolymer, ethylene / vinyl acetate copolymer, and the like. In addition, a multilayer film in which a nylon film or an ethylene vinyl alcohol copolymer (EVOH) is sandwiched between polyethylene or polypropylene films can also be used. Further, a film in which aluminum is vapor-deposited on these films, a film in which glass is vapor-deposited, or a film obtained by laminating these films can also be used.
The thickness of the film is preferably as thin as possible in terms of touch, preferably 100 μm or less, and particularly preferably 50 μm or less. Moreover, in order not to be broken by the sealing conditions at the time of lamination, those of 5 μm or more are preferable.

  More preferably, the means for laminating the film and the foamed gel layer or the foamed liquid layer is such that a nonwoven fabric is laminated on the film in advance, and the foamed liquid is impregnated into the film or the impregnated foamed liquid layer is gelled. As a method for laminating the film and the nonwoven fabric, methods such as an adhesive, heat fusion, and T-die extrusion lamination can be employed. When laminating thin films, for example, by using an adhesive or using a multilayer film in which nylon with high heat resistance is sandwiched between polyethylene films with high heat-fusibility, fine tear holes are generated during lamination. So that it can be heat-sealed.

The laminated sheet is sealed in a container together with the physiologically active gas, so that the physiologically active gas is dissolved in the foamed gel layer or the foamed liquid layer of the laminated sheet and can be maintained in a state where the physiologically active gas is dissolved. At this time, the physiologically active gas is filled in the foamed gel layer or the foamed liquid layer by filling 30% by mass or more, preferably 50% by mass or more, particularly preferably 70% by mass or more in the void gas in the container. The concentration of dissolved bioactive gas can be maintained. Examples of the gas other than the physiologically active gas in the container may include nitrogen gas.
Here, when the physiologically active gas is oxygen, the oxygen concentration in the void gas is measured using a food-use trace oxygen analyzer IS-300 (manufactured by Iijima Electronics Co., Ltd.). When the oxygen concentration of the gas is 25% or less, the normal procedure is followed according to the method of using the measuring instrument. When the oxygen concentration is 25% or more, measurement is performed by mixing a test gas (oxygen) and a gas having no physiological activity other than oxygen (for example, nitrogen gas) at a ratio of 1: 4. Calculated.

(Equation 2)
Void oxygen concentration (%) = measured value (%) × 5

  In addition, when the physiologically active gas is other than oxygen (for example, carbon dioxide), the concentration of oxygen in the void gas is measured using the above-described trace oxygen analyzer for food IS-300, and the measured value is used. It can be easily calculated by the following formula.

(Equation 3)
Void bioactive gas concentration (%) = (20.6−measured value (%)) / 20.6 × 100

  Here, “20.6” indicates the oxygen concentration in the air, and the components other than the gas in the void in the container are assumed to have the same ratio as air.

  The pressure of the gas filled in the packaging pillow (the container internal pressure during storage) is preferably 0.05 to 0.15 MPa, more preferably 0.08 to 0.15 MPa, and particularly preferably 0.09 to 0.12 MPa at 25 ° C. .

  The container-containing sheet of the present invention can be produced, for example, by a method in which the laminated sheet is placed in a container and the gas in the container is then exchanged with a gas having a physiologically active gas of 30% by mass or more. Thus, by adopting a method in which the gas in the container is exchanged with a physiologically active gas under normal pressure and the physiologically active gas is dissolved in the sheet, an adjustment tank for adjusting a highly concentrated physiologically active gas dissolved gel or liquid, There is an advantage that the facility for filling the container in a state where the active gas does not leak becomes unnecessary. As a particularly preferred form, a method of filling a container with a foamed gel or foamed liquid sheet at 25 ° C. and enclosing an appropriate amount of a physiologically active gas can reduce the volume in production and distribution, and the foamed gel or It is also preferable from the viewpoint of saturated dissolution of the physiologically active gas in the foaming liquid. Of course, when filling the physiologically active gas into the container, it may be performed not under normal pressure but under pressure. Since bioactive gases generally have low solubility in aqueous gels and solutions, they are dissolved in the foamed gel layer or foamed liquid layer after filling the packaging container even in the manufacturing process where the bioactive gas is replaced or filled. The amount that is reduced from the void is small. When directly filling the packaging container, it is preferable to calculate the amount dissolved in the foamed gel layer or the foamed liquid layer and fill the amount added to the amount of the physiologically active gas in the void. For example, when a laminated sheet containing a foamed gel layer or a foamed liquid layer is placed in a container and the gas in the container is replaced with 100% concentration oxygen, the amount of oxygen dissolved in the liquid or gel is 1 g of the liquid or gel. In contrast, it becomes approximately 0.03 mL. Moreover, since the oil agent generally has a solubility of oxygen that is about 3 to 10 times higher than that of water, when the oil agent is contained in the foamed gel or the foaming liquid, it is preferable to fill the oxygen in a larger amount depending on the amount of the oil agent. .

  The sheet of the present invention can be conveniently used by taking out the laminated sheet from the container and sticking the foamed gel layer or foamed liquid layer side to the skin.

  Various measurement methods used in Examples are shown below.

(1) Method for measuring carbon dioxide concentration in gel sheet:
Measurements were made using a carbon dioxide electrode (electrode model 9502 BN; Thermo Orion and portable pH / ion meter model 290A; ORION). The gel sheet to be measured is moved to a bottle with a lid containing an alkaline solution, the gel of the sample sheet is dissolved, and then the carbon dioxide generated by returning to acidity with an acidic buffer solution (pH 4.5) is generated using the above electrode. It was measured.

(2) Skin blood flow measurement method:
After acclimatization for 30 minutes in a constant temperature room at 25 ° C., the blood flow in the forearm is measured for 30 seconds with a Doppler blood flow meter (BIOMDICAL SCIENCE Co., LTD LASER FLOWMETER KB-201), and the average value of the values is calculated. As 100, each sheet was affixed to the same part, and after the holding time, the sheet was peeled off, and the blood flow volume at the part was measured and expressed as a relative value.

(3) Method for measuring void oxygen concentration in pillow:
1) A syringe was attached to a 50 mL graduated syringe, and 40 mL was sucked into the syringe from an aluminum pillow filled with 100% nitrogen gas.
2) Further, an additional 10 mL was inhaled from the aluminum pillow containing the sample.
3) The injection needle was removed and the inlet was quickly closed with parafilm.
4) After 1 minute, the sampling needle of a measuring device (micro oxygen analyzer for food IS-300 Iijima Electronics Co., Ltd.) was pierced into the parafilm part, and the oxygen concentration was measured.
The oxygen concentration in the sample void was simply calculated according to the following formula.

(Equation 4)
Void oxygen concentration (%) = measured value (%) × 5
The void portion carbon dioxide concentration was calculated by the simple calculation described above.

(4) Subcutaneous oxygen partial pressure measurement method:
Using a transcutaneous blood gas monitor PO-850A (manufactured by Shinsei Electronics Co., Ltd.) as a measuring device, the measurement was simply performed by the following method.
First, as a control, a sheet in which air in the pillow was not replaced with oxygen and was kept as air was applied to the skin on the inner side of the forearm for 5 minutes. Immediately after removing the sheet, the sheet application part was wiped with a tissue and immediately attached to the skin of the sheet application part without heating the sensor of the measuring instrument. The oxygen partial pressure measurement value was read every 10 seconds until 2 minutes after the attachment, and the oxygen partial pressure measurement value was read every 30 seconds until 10 minutes thereafter. Oxygen partial pressure measurement values were plotted on a graph against the time after wearing the sensor, a straight line was drawn so that the measured values immediately after wearing the sensor were in contact with each other, and the slope of the straight line, that is, the rate of decrease in skin surface oxygen partial pressure was obtained. . In addition, a value that became almost constant in the vicinity of 10 minutes in the latter half of the measurement was defined as the subcutaneous oxygen partial pressure of control. The subcutaneous oxygen partial pressure of the control was almost 10 mmHg. The measurement was performed in the same manner as the control when the sample sheet was applied. Assuming that the skin surface oxygen partial pressure reduction rate is proportional to the difference between the external oxygen partial pressure (160 mmHg) and the subcutaneous oxygen partial pressure, the subcutaneous oxygen partial pressure when applying the sample sheet was determined according to the following equation.
Subcutaneous oxygen partial pressure (mmHg) at the time of application of the sample sheet = 160 mmHg− (Skin surface oxygen partial pressure decrease rate at the time of sample sheet application / control skin surface oxygen partial pressure decrease rate) × (160 mmHg−10 mmHg)

<Preparation of a bubble-containing sheet>
(1) Air-containing gel sheet A
On a non-woven fabric (rayon: acrylic: PE = 50: 25: 25; basis weight 35 g / m ² ; thickness 0.1 mm), LDPE resin was extruded as a single layer at 210 ° C. in a single layer so as to have a film thickness of 15 μm. Thus, a laminated sheet was prepared (carbon dioxide permeability of film: 12,000 cc / m ² · day · atm).
Components other than the magnesium metasilicate aluminate in Table 1 gel formulation were mixed and stirred for 7 minutes with a universal mixing stirrer (manufactured by Dalton Co., Ltd.) equipped with a whipper as a stirring tool. The bubble rate was 26.7%. Magnesium aluminate metasilicate was added and further stirred with a whipper for 30 seconds. The cell content of the obtained cell-containing gel was 30.3%. A foam-containing gel is placed on the nonwoven fabric surface of the laminated sheet, and further covered with a 50 μm PET film, and then stretched to a thickness of 1 mm using a bar coater and left at room temperature for 2 days to form a cross-linked gel. A bubble-containing gel sheet A was prepared (at the time of skin application, the PET film on one side was peeled off, and the peeled gel surface was applied to the skin). In addition, in the interface of a film and a foaming gel layer, the nonwoven fabric laminated | stacked on the film showed an anchor effect because it entered into a part of foaming gel layer, and the film and the foaming gel layer were adhere | attached firmly.

(2) Air-containing gel sheet B
In addition, the same cell-containing gel is sandwiched between two 50 μm PET films, stretched to a thickness of 1 mm using a bar coater, and allowed to crosslink and gel at room temperature for 2 days. (At the time of skin application, the PET film on both sides was peeled off, and either side was applied to the skin).

(3) Cell-containing gel sheet C
Table 1 Components other than magnesium aluminate metasilicate of gel formulation were mixed and put into a universal mixing stirrer (manufactured by Dalton Co., Ltd.) equipped with a hook as a stirring tool, and reduced to -0.09 MPa with a vacuum pump for 7 minutes. Stir. After the stirring was stopped, the pressure was gradually returned to normal pressure. Magnesium aluminate metasilicate was added, and the mixture was lightly stirred, and then the pressure was reduced again to -0.09 MPa with a vacuum pump, and the mixture was further stirred for 30 seconds. After the stirring was stopped, the pressure was gradually returned to normal pressure. The resulting gel had an air bubble ratio of 0.8%. The gel is placed on the nonwoven fabric surface of the laminated sheet, covered with a 50 μm PET film, stretched to a thickness of 0.7 mm using a bar coater, and left at room temperature for 2 days to form a cross-linked gel. A bubble-containing gel sheet B (comparative gel sheet) was prepared (at the time of skin application, the PET film on one side was peeled off and the peeled gel surface was applied to the skin).

Example 1
A bubble-containing sheet A with a film having a thickness of 1 mm was cut into a size of 70 mm × 50 mm, sealed with 100% carbon dioxide in an aluminum pillow, closed with an impulse sealer, and allowed to stand at room temperature for 7 days to prepare a sample sheet A in a container. The weight of one sample sheet was 2.5 g. After measuring the void portion carbon dioxide concentration in the aluminum pillow containing the sample sheet A, the aluminum pillow was opened, the PET film on one side was peeled off, and the carbon dioxide concentration in the gel immediately after opening was measured. A total of 3 samples were measured and the average value of each carbon dioxide concentration was determined.
Moreover, the aluminum pillow containing the sample sheet A was opened, the PET film on one side was peeled off, placed on the skin on the inner side of the forearm so that the peeled gel surface was on the skin side, and held for 10 minutes. The skin flushing of the skin after the sheet removal was visually confirmed, and the skin blood flow and the carbon dioxide concentration in the gel sheet were measured. For skin flushing, the clarity of the boundary between the applied part and the non-applied part was evaluated in the following five levels.
5: The boundary is clear 4: The boundary is slightly clear 3: The boundary is slightly recognizable 2: The boundary is blurred 1: The test is performed once for three measurement panels in which no boundary is recognized at all The average value of skin flush and carbon dioxide concentration was determined. The results are shown in Table 2.

  A sample sheet B containing a container was prepared in the same manner as in Example 1 except that the film-free cell-containing gel sheet B having a thickness of 1 mm was used, and the same test was performed. The weight of one sample sheet was 2.5 g, and the test was conducted by removing the PET film on both sides when applying the skin. The results are shown in Table 2.

  A sample sheet C with a container was prepared in the same manner as in Example 1 except that the air-containing gel sheet C with a film having a thickness of 0.7 mm was used, and the same test was performed. The weight of one sample sheet was 2.5 g. The results are shown in Table 2.

  Sample sheet A of the present invention (gel bubble ratio of 30.3%) retained a high carbon dioxide concentration of 1000 ppm or more even after 10 minutes of skin application, and a sufficient blood flow promoting effect was observed. On the other hand, even if the weight and the bubble ratio of the gel were the same as those of the sample sheet A, in the sample sheet B without the film, the carbon dioxide concentration was reduced to 100 ppm or less, and blood flow promotion was not recognized. Similarly to sample sheet A, sample sheet C with a film with the same gel weight and low bubble rate (bubble rate 0.8%) has a carbon dioxide concentration of 500 ppm or less after 10 minutes of skin application. The blood flow promoting effect was not sufficient.

<Preparation of a bubble-containing sheet>
(1) Cell-containing gel sheet D
On a non-woven fabric (rayon: acrylic: PE = 50: 25: 25; basis weight 35 g / m ² ; thickness 0.1 mm), EVOH resin is extruded as a single layer at 250 ° C. in a single layer so as to have a film thickness of 15 μm. Thus, a laminated sheet was prepared (film oxygen permeability of 10 cc / m ² · day · atm). A bubble-containing gel sheet D was prepared in the same manner as the preparation of the bubble-containing gel sheet A laminated with LDPE except that the thickness of the sheet was 1.4 mm using an EVOH laminate sheet.

(2) Preparation of cell-containing gel sheets E and F Except that the thickness of the sheet was 1.4 mm using an EVOH laminated sheet, the film-containing gel sheet C was prepared in the same manner as the cell-containing cell-containing gel sheet C laminated with LDPE. A foam gel sheet E was prepared. In addition, an air-containing gel sheet F with a film having a sheet thickness of 1 mm was prepared.

Example 2
A film-containing bubble-containing sheet D having a thickness of 1.4 mm was cut into the shape shown in FIG. 1, sealed in an aluminum pillow with 100% oxygen, closed with an impulse sealer, and further allowed to stand at room temperature for 7 days to prepare a sample sheet D. The weight of one sample sheet D was 3.0 g.
In addition, as a control for measuring the subcutaneous oxygen partial pressure, a control sheet enclosed in an aluminum pillow without gas replacement was also prepared at the same time.
The oxygen concentration in the voids in the aluminum pillow of the sample sheet was measured. A total of three samples were measured to obtain an average value of oxygen concentration.

  The aluminum pillow was opened, the PET film on one side was peeled off, applied to the inner side of the forearm so that the peeled gel surface was on the skin side, and held for 20 minutes. While visually checking the white spots of the skin after the sheet was removed, the subcutaneous oxygen partial pressure was measured. As for the white spots on the skin, the clarity of the boundary between the applied part and the non-applied part was evaluated based on the same five-step criteria as in Example 1.

On the other hand, the fit on the face was also evaluated. The aluminum pillow was opened, the PET film on one side of the sample sheet was peeled off, applied to the skin under the eyes so that the peeled gel surface was on the skin side, and held for 20 minutes. The fit during application was evaluated on a four-point scale, with no peeling feeling: 4, with some peeling feeling: 3, with peeling feeling: 2, and peeling off: 1.
The test was performed once for each of the three measurement panels, and the average values of skin whitening, subcutaneous oxygen partial pressure, and fit were obtained. The results are shown in Table 3.

  A sample sheet E was prepared in the same manner as in Example 2 using an air-containing gel sheet E with a film having a thickness of 1.4 mm, and a sample sheet F was prepared using an air-containing gel sheet F with a film having a thickness of 1 mm, and the same test was performed. . The weight of one sample sheet E was 4.3 g, and the weight of one sample sheet F was 3.0 g. The results are shown in Table 3.

  Sample sheet D with an EVOH film, a bubble rate of 30.3%, and a thickness of 1.4 mm had a good fit to the skin because oxygen penetrated subcutaneously and white spots were observed. On the other hand, the sample sheet E having a foam ratio of 0.8% in the foamed gel layer was heavier than the sample sheet D and had a poor fit, and the subcutaneous oxygen partial pressure was low and the degree of white spots was low. In addition, the sample sheet F having a thickness of 1 mm has a good fit to the skin because of the same weight as the sample sheet D. However, since the bubble ratio is as low as 0.8%, the subcutaneous oxygen partial pressure is low. The degree of white spots was also low.

Claims (7)

  A layered sheet of foamed gel layer or foamed liquid layer containing bubbles with a cell rate of 5 to 50% and a resin film is hermetically sealed in a gas-impermeable container. A body-attaching sheet containing 30% by mass or more of a physiologically active gas.   The sheet according to claim 1, wherein the gas having physiological activity on the body is oxygen or carbon dioxide.   The sheet according to claim 1 or 2, wherein the pressure inside the container during storage is 0.05 to 0.15 MPa. The sheet according to any one of claims 1 to 3, wherein the gas permeability of the resin film is 20,000 cc / m ² · day · atm or less.   The sheet according to any one of claims 1 to 4, wherein the foamed gel layer is a foamed aqueous gel layer formed of an anionic polymer and a polyvalent cation.   The sheet according to any one of claims 1 to 5, wherein the foamed gel layer or the foamed liquid layer contains an oil component.   A sheet in which a foamed gel layer or a foamed liquid layer containing bubbles with a bubble rate of 5 to 50% and a resin film are laminated is placed in a gas-impermeable container, and then the body is physiologically placed in the void in the container. A method for producing a body-applied sheet containing a container, wherein an active gas is filled to 30% by mass or more and then the container is sealed.

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