JP2019124667A - Skin adhesive material, and method for collecting skin secretion and method for measuring biological component using skin adhesive material - Google Patents

Abstract

To provide construction of a technology capable of collecting a skin secretion such as sweat secreted from any arbitrary part and an arbitrary area of a living body without leaking, construction of a technology capable of collecting a skin secretion such as a very small amount of sweat, and construction of a technology capable of acquiring highly reliable biological information from skin secretions such as sweat.SOLUTION: The method for collecting a skin secretion and a method for measuring a biological component includes a hydrogel layer holding water and a polyhydric alcohol within a 3-dimensional structure of a hydrophilic polymer having crosslinking, in which the skin adhesive for collecting skin secretions, a skin adhesive for measuring biological components, and a skin adhesive in which a hydrogel layer is adhered to the skin and the skin secretion is absorbed.SELECTED DRAWING: Figure 6

Description

  The present invention relates to a skin adhesive, a method for collecting skin secretions using the skin adhesive, and a method for measuring a biological component.

  Conventionally, biological information such as blood sugar level which is an index of onset and management of diabetes and blood lactate level which is an index of exercise intensity and fatigue is acquired by collecting blood and measuring biological components in the blood. Is common. However, blood collection involves mental and physical burden, as well as the risk of infection. Therefore, techniques for collecting sweat and measuring biological components contained in the sweat are becoming widespread. Sweats can be collected non-invasively and non-invasively and there is no risk of infection at the time of collection. In addition, since sweat is one of the in vivo metabolic pathways, various biological information can be obtained by measuring biological components contained in sweat.

  For example, the finger is brought into contact with a liquid such as ethanol, butylene glycol, or an aqueous solution of alcohol such as ethylene glycol filled in a container capable of containing a fingertip, and the sweat and the biological components contained in the sweat are eluted in the fluid. Techniques for collecting sweat and the like secreted from fingertips have been reported (see Patent Document 1 and Non-patent Document 1 etc.). Furthermore, it is disclosed about the measurement of the sugar value and the lactic acid value contained in the extract | collected sweat.

  Moreover, the technique which coat | covers arbitrary site | parts of the skin surface with a film etc., and collect perspiration by absorbing perspiration in a storage or absorption sheet is reported (for example, nonpatent literature 2, and patent documents 2 and 3) Etc.). Specifically, in Non-Patent Document 2, a film such as parafilm is attached to an arbitrary part of the skin surface, and sweat collected and leaked from the opening provided at the central part is collected with a pipette, capillary tube or the like. A method of aspiration and collection is disclosed. Patent Document 2 discloses a liquid (sweat) collecting device formed of a synthetic resin material. The liquid collection device is provided with a collection unit that is sealed when mounted on the skin to collect sweat, and a discharge unit that discharges the sweat collected by the collection unit from the collection unit, and collects the sweat. Furthermore, it is disclosed about the measurement of the lactic acid level contained in collected sweat. In Patent Document 3, a sweat-absorbing sheet such as filter paper or glass fiber is disposed in close contact with the skin between a film covering the skin surface and the skin, and the sweat-absorbing sheet absorbs sweat. A sweat collection device for collecting

  In addition, sweat induction is induced by a sweat inducing device based on pilocarpine iontophoresis, and a sweat collector (Macroduct® sweat collector) equipped with a spiral thin tube is attached to the perspiration position on the skin surface, and the inside thereof Have been reported (see, eg, Non-Patent Document 3). Furthermore, it is disclosed about the measurement of the chloride value and the sulfate value contained in the collected sweat.

JP 2005-230188 A JP, 2017-80245, A Japanese Patent Application Laid-Open No. 2004-216020

T. Ohkuwa et al., “The relationship between exercise intensity and lactate concentration on the skin surface”, International Journal of Biomedical science, 2009, Vol. 5, No. 1, p23-27 G. R. Brisson et al., "A simple and disposable sweat collector", European Journal of Applied Physiology and Occupational Physiology, 1991, Vol. 63, p269-272. David E. C. Cole et al., "Use of a new sample-collection device (MacroductTM) in anion analysis of human sweat", Clinical Chemistry, 1986, Vol. 32, No. 7, p1375-p1378

  However, the techniques disclosed in Patent Document 1 and Non-patent Document 1 are methods for eluting sweat and biological components contained in sweat into a liquid by bringing a very small amount of liquid into contact with the skin surface. Therefore, there is a problem that the contact area with the liquid changes every measurement. Furthermore, it is expected that it will be difficult to collect all the fluid in contact with the skin surface, and it will be difficult to accurately measure the biological components contained in the sweat.

Further, the techniques disclosed in Non-Patent Document 2 and Patent Documents 2 and 3 collect fluid-like sweat secreted from the skin by suction or absorption in an absorbent sheet. Therefore, it is not suitable for collecting an extremely small amount of sweat. For example, sweat released from the skin at rest is generally a very small amount of 0.1 mg / cm ² / min, and therefore it can be collected by the techniques disclosed in Patent Document 2 and Patent Documents 2 and 3. It is expected to be difficult.

  The technique disclosed in Non-Patent Document 3 is to induce sweating using pilocarpine. However, the sweat that is secreted due to the drug's stimulation may not reflect biological information correctly because the amount of perspiration and the abundance ratio of biological components contained in the sweat are different from sweat by natural secretion. is there. In addition, there is also a problem that it is not suitable for accurate measurement of sweat rate or trace sweating.

  Then, this invention makes it a subject the construction | assembly of the technique which can be extract | collected, without leaking skin secretions, such as a sweat etc. which are secreted from the skin of any arbitrary part and area | region of a biological body. Furthermore, the task is to construct a technology that can also collect skin secretions such as trace amounts of sweat. Another object of the present invention is to construct a technology capable of acquiring highly reliable biological information from skin secretions such as sweat.

  The inventors of the present invention have conducted intensive studies to solve the above problems, and a hydrogel layer containing water and polyhydric alcohol is contained in a three-dimensional structure of a hydrophilic polymer having intermolecular and / or intramolecular crosslinks. Can exhibit excellent absorbability of skin secretions such as sweat secreted from the skin, and can also exhibit excellent wearability on the skin surface, and efficiently produce skin secretions such as trace amounts of sweat. I found that I could collect it. In addition, the hydrogel layer is applicable to any arbitrary part of the living body and the skin surface of any area. Furthermore, it has been found that reliable biological information can be obtained from skin secretions such as sweat through the hydrogel layer. The present invention has been completed based on these findings.

  That is, in order to solve the above-mentioned subject, the invention shown in the following [1]-[8] is provided.

[1] A skin secretion comprising a hydrogel layer holding water and a polyhydric alcohol in a three-dimensional structure of a hydrophilic polymer having crosslinks, wherein the hydrogel layer adheres to the skin surface and absorbs skin secretions Skin adhesive for collection of objects.
[2] The skin adhesive of the above-mentioned [1], wherein the hydrophilic polymer is a poly (meth) acrylamide polymer.
[3] The skin adhesive of the above-mentioned [1] or [2], wherein the polyhydric alcohol is glycerol.

  According to the configuration of the above [1] to [3], a skin adhesive material capable of collecting non-invasive, non-invasive and safe skin secretions such as sweat and skin gas secreted from the skin. Can be provided. The skin adhesive material can absorb skin secretions from any area of the skin surface without leakage at any arbitrary site on the skin surface, and is also suitable for collecting trace amounts of skin secretions. In particular, according to the constitution of the above [2], it is possible to provide a skin adhesive which can be easily prepared and is excellent in flexibility and absorption performance, and according to the constitution of the above [3], it is inexpensive and handleable. It is possible to provide a skin adhesive which is easy and has a suitable adhesion.

[4] The skin adhesive according to any one of the above [1] to [3] for measuring a biological component contained in the skin secretion.
[5] The skin adhesive of the above-mentioned [4], wherein the biological component is glucose or lactic acid.

  According to the constitutions of the above [4] to [5], biological components contained in skin secretions such as sweat and skin gas secreted from the skin can be noninvasively, noninvasively and safely measured. Can provide a skin adhesive that can be used to In addition, since the skin adhesive can absorb skin secretion from any area of the skin surface without leaking it at any arbitrary site on the skin surface, it is possible to measure the biological components contained in the absorbed skin secretion, Reliable biometric information can be obtained. In particular, according to the constitution of [5], glucose is used as an index for diagnosis and management of diabetes etc. and lactic acid is used as an index for physical stress such as muscle fatigue and blood circulation failure. It is possible to provide a skin adhesive that can

[6] A step of adhering the skin adhesive material of any one of the above [1] to [3] to the skin surface and absorbing the skin secretion in the hydrogel layer to collect the skin secretion A method of collecting skin secretions.

  According to the configuration of the above [6], there is provided a method of collecting a skin secretion which can collect skin secretions such as sweat and skin gas which are noninvasively, noninvasively and safely secreted from the skin. Can be provided. The method of collecting the skin secretion can absorb the skin secretion from the skin surface of any area without leaking at any arbitrary site on the skin surface by using the skin adhesive material of the present invention, and the skin secretion of a very small amount It is also suitable for collecting things. Furthermore, the method for collecting skin secretion can perform collection of local continuous skin secretion.

[7] A step of collecting the skin secretion by adhering the skin adhesive of any one of the above [1] to [3] to the skin surface and absorbing the skin secretion in the hydrogel layer When,
And e. Eluting the biological component contained in the skin secretion absorbed in the hydrogel layer of the skin adhesive separated from the skin surface, and measuring the eluted biological component. How to measure
[8] The method for measuring a biological component of the above-mentioned [7], wherein the biological component is glucose or lactic acid.

  According to the configuration of the above [7] or [8], biological components contained in skin secretions such as sweat and skin gas secreted from the skin are noninvasively, noninvasively and safely measured. The present invention can provide a method of measuring a biological component that can be used to In addition, the method of measuring the biological component can be absorbed skin secretions by using the skin adhesive material of the present invention and being able to absorb skin secretions from any area of the skin surface without leaking at any arbitrary site on the skin surface. By measuring the biological component contained therein, highly reliable biological information can be obtained. Furthermore, the method of measuring the biological component can measure the biological component in the local continuous skin secretion. In particular, according to the constitution of [8], glucose can be used as an index for diagnosis and management of diabetes etc. and lactic acid can be used as an index for physical stress such as muscle fatigue and thermal fatigue. A method of measuring a biological component can be provided.

It is a figure which shows an example of the usage condition of the skin adhesive which concerns on embodiment of this invention. In Example 4 which verified the absorption performance of the sweat of the skin adhesive material which concerns on embodiment of this invention, it is a figure which shows the collection site | part of the sweat by the said skin adhesive material. It is a graph which shows the result of Example 4 which verified the absorption performance of the sweat of the skin adhesive material which concerns on embodiment of this invention, a vertical axis is the amount of sweat absorption (mg), and a horizontal axis is a sweat collection site. It is a graph which shows the result of Example 5 which verified the measurement of the living body ingredient contained in the sweat collected with the skin adhesive concerning the embodiment of the present invention, and a vertical axis is the amount (mM) of lactic acid, horizontal axis Is the sweat collection site. It is a graph which shows the result of Example 6 which verified the continuous absorption performance of the sweat of the skin adhesive material which concerns on embodiment of this invention, a vertical axis is the amount of sweat absorption (mg), and a horizontal axis is exercise load conditions. . It is a graph which shows the result of Example 7 which verified the continuous measurement of the biological component contained in the sweat extract | collected with the skin adhesive which concerns on embodiment of this invention, and a vertical axis is lactic acid amount (mM), horizontal The axis is the exercise load condition. It is a graph which shows the result of Example 8 which verified the continuous collection of sweat from sites other than a finger tip, and a vertical axis is a sweat absorption amount (mg), and a horizontal axis is a sweat collection site. It is a graph which shows the result of Example 9 which verified verification of measurement of a living body ingredient contained in sweat collected from sites other than a finger tip by skin adhesive concerning an embodiment of the present invention, and a vertical axis is lactic acid in sweat. Amount (nmol / cm ² / min), the horizontal axis is the exercise load condition. It is a graph which shows the result of Example 10 which examined the correlation with the blood concentration of the living body constituent concentration in the sweat absorbed by the skin adhesive concerning the embodiment of the present invention, and a vertical axis is lactic acid in sweat. Amount (nmol / cm ² / min), the horizontal axis is blood lactate concentration (mM).

(Skin adhesive material)
The skin adhesive according to the present embodiment includes a hydrogel layer holding water and a polyhydric alcohol in a three-dimensional structure of a cross-linked hydrophilic polymer.

  The hydrogel layer in the skin adhesive according to the present embodiment has, for example, a skeleton of a network-like three-dimensional structure formed by crosslinking between hydrophilic polymers and / or in hydrophilic polymers, and the skeleton thereof A structure that holds a large amount of lost aqueous solvent in the gap between The hydrogel layer also includes those in which only the surface forms a skeleton of a network-like three-dimensional structure, and in the region surrounded by the skeleton, the aqueous solvent is held and the like.

The hydrophilic polymer which comprises the hydrogel layer in the skin adhesive material which concerns on this embodiment is a polymer which has a hydrophilic functional group in the principal chain. As a hydrophilic functional group, for example, a hydroxyl group, a phosphoric acid group, a phosphonic acid group, a phosphinic acid group, a sulfonic acid group, a sulfin group, a sulfene group, a carboxyl group, a thiol group, an amide group, a primary amino group, a secondary amino Examples thereof include a group (-NHR), a tertiary amino group (-NR ₂ ), a quaternary ammonium group (-NR ₃ ⁺ ) and the like, and one of these may be contained alone, or two or more may be contained. However, it is not limited to these. In addition, it may contain a betaine structure.

  The hydrophilic polymer may be a synthetic polymer or a natural polymer, but is preferably a synthetic polymer from the viewpoint of gel strength. In addition, when the skin adhesive according to the present embodiment is used to measure a biological component, it is a non-ion-exchangeable hydrophilic polymer from the viewpoint of the elution of the biological component from the hydrogel layer, etc. Is preferred.

  Specific examples of hydrophilic synthetic polymers include (meth) acrylamide, N-methyl (meth) acrylamide, N-ethyl (meth) acrylamide, N-propyl (meth) acrylamide and N-isopropyl (meth) acrylamide (Meth) acrylamides such as N, N-dimethyl (meth) acrylamide, N, N-diethyl (meth) acrylamide, N, N-dimethylaminoethyl (meth) acrylamide, N, N-dimethylaminopropyl (meth) acrylamide and the like Monomer, (meth) acrylic acid, 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, 2- (methylamino) ethyl (meth) acrylate, 2- (meth) acrylate (Meth) acrylic acid based monomers such as dimethylamino) ethyl, 2- (diethylamino) ethyl (meth) acrylate, or ) Sodium acrylate, salts of (meth) acrylic acid monomers such as potassium (meth) acrylate, vinyl alcohol monomers, vinyl pyrrolidone, N-vinyl acetamide, N-methyl-N-vinyl acetamide, N-vinyl formamide, etc. Homopolymers obtained by polymerizing one kind of polymerizable hydrophilic monomers such as vinylamide monomers, vinyl sulfonic acid monomers, and maleic acid monomers of the above, or copolymers obtained by polymerizing two or more kinds. However, it is not limited to these. In the case of a copolymer, it may be a copolymer with a polymerizable hydrophobic monomer as long as the hydrophilic property is not lost. Preferably, a poly (meth) acrylamide-based polymer which is a polymer of a (meth) acrylamide-based monomer which can be easily polymerized can be used. In addition, "(meth) acryl" means "acryl" or "methacryl", and "(meth) acrylic acid" means "acrylic acid" or "methacrylic acid."

  Specific examples of hydrophilic natural polymers include agarose, collagen, gelatin, dextran, alginic acid and derivatives thereof, kappa (κ) -carrageenan and derivatives thereof, iota (ι) -carrageenan and derivatives thereof, native gellan gum and the like Gellan gum and derivatives thereof such as deacylated gellan gum, pectin and derivatives thereof, xanthan gum and derivatives thereof, carboxymethylcellulose and derivatives thereof, gels such as hyaluronic acid and derivatives thereof and the like but not limited thereto.

  The hydrophilic polymer is crosslinked between polymers and / or in the polymer. Crosslinking may be by covalent bonding or by interaction such as hydrogen bonding, and may be appropriately selected according to the type of hydrophilic polymer and the like. In the case of crosslinking by covalent bonding, for example, crosslinking can be performed by using a polyfunctional reagent. Specific examples of polyfunctional reagents include polyfunctional (meth) acrylamide monomers such as N, N'-methylenebis (meth) acrylamide, N, N'-ethylenebis (meth) acrylamide, and monoethylene glycol Di (meth) acrylic acid, ethylene glycol di (meth) acrylic acid, diethylene glycol di (meth) acrylic acid, propylene glycol di (meth) acrylic acid, dipropylene glycol di (meth) acrylic acid, triethylene glycol di (meth) Polyfunctional acrylic acid monomers such as acrylic acid, triethylene glycol di (meth) acrylic acid, tetraethylene glycol di (meth) acrylic acid, tripropylene glycol di (meth) acrylic acid, divinyl benzene, divinyl sulfone, divinyl Biphenyl, Diethyleneg Multifunctional monomers such as multifunctional divinyl monomers such as cole divinyl ether, aldehydes such as glutaraldehyde, glycidyl ethers such as ethylene glycol diglycidyl ether, ethylene propylene diglycidyl ether, glycerol polyglycidyl ether, hexamethylene Isocyanates such as diisocyanate, carbodiimides and the like can be mentioned, and one of these can be used alone, or two or more can be used. However, it is not limited to these. When crosslinking using a polyfunctional monomer, it can be made into a copolymer with the above-mentioned hydrophilic monomer. In addition, crosslinking using ions, pH, light, heat and the like may be used.

  The hydrophilic polymer is preferably 1 to 20% by weight, particularly preferably 1 to 10% by weight, based on the total weight of the hydrogel layer. Within the above range, appropriate gel strength and gel stability can be imparted to the hydrogel layer while maintaining good flexibility and absorption of skin secretions. When crosslinking of the hydrophilic polymer is carried out by copolymerization of a hydrophilic monomer and a polyfunctional monomer, it is preferable to include the polyfunctional monomer in an amount of 0.1 to 1.0% by weight based on the hydrophilic monomer, and particularly preferable. Is 0.1 to 0.5% by weight. If the above range is exceeded, the crosslink density may be too high, and the flexibility of the hydrogel layer and the absorbability of the skin secretion may be reduced. If the above range is not satisfied, the crosslink density may be too low and the hydrogel layer Gel strength and gel stability may decrease.

  The hydrogel layer contained in the skin adhesive according to the present embodiment contains water and a polyhydric alcohol. By containing a polyhydric alcohol in the hydrogel layer, it is possible to enhance the adhesion performance of the hydrogel layer and the absorption performance of skin secretions. The polyhydric alcohol is an alcohol having two or more hydrogen groups in the molecule, and examples thereof include, but are not limited to, sugar alcohols, sugars, and glycols. Here, the sugar alcohol is a polyhydroxyalkane obtained by reducing a carbonyl group of aldose or ketose, and a polyhydroxycycloalkane. Specific examples thereof include glycerol (glycerin), erythritol, threitol, arabinitol, xylitol, ribitol, galactitol, sorbitol, mannitol, inositol and the like, but are not limited thereto. The saccharides are classified into a monosaccharide as a component, and an aldose which is a saccharide having an aldehyde group and a ketose which is a saccharide having a ketone group. Specific examples include monosaccharides such as glyceraldehyde, erythrose, threose, arabinose, xylose, ribose, galactose, sorbose and mannose, and polysaccharides such as disaccharides such as trehalose, fructose, sucrose and lactose. Not limited to these. Glycols are aliphatic dihydric alcohols. Specifically, ethylene glycol, prolene glycol, diethylene glycol and the like can be mentioned, but it is not limited thereto. The polyhydric alcohol may contain one kind alone or a mixture of two or more kinds. Preferably, inexpensive and easy-to-handle glycerol can be used as the polyhydric alcohol.

  It is preferable that it is 80 to 99 weight% with respect to the total weight of a hydrogel layer, and, as for the liquid component of water and polyhydric alcohol, it is especially preferable that it is 90 to 95 weight%. If it is in the said range, appropriate gel strength and gel stability can be provided to a hydrogel layer, maintaining a favorable softness | flexibility and absorption capability. The polyhydric alcohol is preferably 10 to 80% by weight, particularly preferably 50 to 80% by weight, based on the total weight of the hydrogel layer. If it is in the said range, moderate adhesive force can be provided to a hydrogel layer.

  The hydrogel layer contained in the skin adhesive according to the present embodiment further contains additives such as preservatives, antioxidants, stabilizers, dispersants, buffer components, and various medicinal components and various cosmetic components ( For example, lotions, aroma oils, perfumes, etc. may be included as necessary.

  The shape of the hydrogel layer contained in the skin adhesive material according to the present embodiment is not particularly limited, but may be appropriately set to plate, cube, column, rod, fiber, sphere, particle, block, etc. It is preferably formed into a thin sheet. Further, the contact surface with the skin surface can be appropriately set to a square, a rectangle, a circle, a substantially elliptical shape, or the like.

The size of the hydrogel layer contained in the skin adhesive according to the present embodiment is not particularly limited, and can be appropriately set according to the skin surface to be a collection target of the skin secretion. For example, when the skin adhesive material is formed into a sheet, the area of the contact surface with the skin surface can be 1 to 200 cm ² , and the thickness can be 0.1 to 1.0 mm, but the size is limited It is not something to do. The weight per unit area of the hydrogel layer is preferably 0.01 to 1.0 g / cm ^2, particularly preferably be a 0.05 to 0.3 g / cm ^2, and not limitation, hydrophilic polymers It can change suitably according to the kind etc. of.

  The hydrogel layer contained in the skin adhesive according to the present embodiment can be produced by a method known in the art. For example, by polymerization / crosslinking reaction of a polymerization composition in which a hydrophilic monomer, a polyfunctional monomer, water, a polyhydric alcohol, a suitable polymerization initiator, and an additive which is optionally added are mixed. A hydrogel layer can be obtained. The polymerization initiator is not particularly limited. For example, azo compounds such as 2,2'-azobisisobutyronitrile, 1,1'-azobis (cyclohexane-1-carbonitrile), benzoyl peroxide, lauryl peroxide, excess Examples include organic peroxides such as tert-butyl oxide, and redox initiators such as hydrogen peroxide-ferrous iron ion. The polymerization reaction can be carried out by radical polymerization, anionic polymerization or cationic polymerization depending on the type of polymerization initiator and monomer. Although it does not limit, it can carry out by heating the composition for superposition | polymerization mentioned above, for example, for 1 hour or more and 30 hours or less at the temperature of 0 degreeC or more and 80 degrees C or less, under stirring. When a natural polymer is used, it is gelled by a gelation method according to the type of natural polymer, and at this time, the hydrogel layer can also be formed by performing a crosslinking reaction with a polyfunctional reagent as necessary. You can get it.

  In the skin adhesive according to the present embodiment, a release liner that can be peeled off at the time of use may be provided on the surface of the hydrogel layer. Thereby, it is possible to prevent foreign matter from adhering to the skin adhesive material and lowering the adhesive performance until the time of use. In use, the release liner can release to and from the hydrogel layer surface.

  The skin adhesive according to the present embodiment adheres to the skin surface and collects skin secretions secreted from the skin. Here, the skin is a structure covering the body surface of the animal, and is composed of the epidermis present in the surface layer and the dermis of connective tissue, and the appendages such as hair with deformed epidermis, nails, sweat glands and sebaceous glands It is included. The skin in the skin adhesive according to the present embodiment is the skin of an animal capable of secreting skin secretions, and in particular, the skin of an animal capable of secreting skin secretions such as sweat, skin gas, sebum, etc. It is. Here, sweat is secreted from the sweat glands. Skin gas is derived from blood which volatile components in the blood directly release from the skin, from skin glands released from skin glands such as sweat glands and sebaceous glands, and sweat and sebum secreted from skin glands There are those derived from skin surface reactions in which components are oxidized and degraded by the action of skin resident bacteria and the like to release volatile components. Sebum is secreted from the sebaceous glands. Therefore, the skin targeted for the skin adhesive material according to the present embodiment is preferably one having skin glands such as sweat glands and sebaceous glands, or one having blood vessels distributed in the vicinity of the epidermis. Furthermore, they are present on the back side of the limbs of animals such as canines, felines, and bears, and they include meat balls having sweat glands and the like. Therefore, animals can be applied to various animals such as canines, felines, and bears, as well as animals having developed sweat glands, such as humans and horses, and animals belonging to some rodents.

  The hydrogel layer contained in the skin adhesive according to the present embodiment contains a polyhydric alcohol and thus has good adhesion performance to the skin surface. That is, the skin adhesive according to the present embodiment adheres directly to the skin surface, and has an adhesive strength that can withstand not only rest, but also low strength to high strength exercise and the like. On the other hand, it has an adhesive force that can be performed smoothly without peeling after use and without accompanying pain or residue of hydrogel layer fragments on the skin surface. In addition, since the hydrogel layer is highly biocompatible, when applied to the skin, adverse effects such as toxicity, irritation and allergic reaction can be suppressed.

  The skin adhesive according to the present embodiment can adhere to any arbitrary part of the skin surface, that is, the outer surface of the living body. That is, the hydrogel layer contained in the skin adhesive according to the present embodiment has flexibility by containing a large amount of water. Therefore, the skin adhesive according to the present embodiment can be applied to any arbitrary part of the skin surface including the part where complex movements such as bending parts are performed, and without peeling off even complex movements of the skin surface. It can follow. For example, head such as forehead and earlobe, arm such as forearm and palm, finger tip and the like, thigh and lower leg, leg such as foot sole, torso such as neck, chest and abdomen, etc. may be mentioned. It is not something to do. In addition, the skin adhesive according to the present embodiment can be safely applied to the skin surface of any arbitrary part also because it does not contain a metal component or the like.

  Furthermore, the skin adhesive according to the present embodiment can be arbitrarily set to the area of the skin secretion collection site on the skin surface by controlling the area of the adhesive region of the hydrogel layer with the skin surface. it can.

The skin adhesive according to the present embodiment can absorb skin secretions such as sweat, skin gas and sebum secreted from the skin. That is, the hydrogel layer contained in the skin adhesive according to the present embodiment has high absorption performance, and absorbs skin secretion in the three-dimensional structure and swells. As described above, since the skin adhesive according to the present embodiment adheres to the skin surface of any area at any arbitrary site on the skin surface, the skin from the skin surface of any area at any arbitrary site on the skin surface Secretions can be absorbed without leaking. Therefore, it is possible to collect skin secretions such as trace amounts of sweat which are secreted at rest or in a short time. For example, in the case of sweat, 0.1 mg to 20 mg / cm ² / minute can be collected.

  As described above, the skin adhesive according to the present embodiment can collect skin secretions non-invasively, non-invasively and safely secreted from the skin. The skin adhesive material can absorb skin secretions from any area of the skin surface without leakage at any arbitrary site on the skin surface, and is also suitable for collecting trace amounts of skin secretions.

  In addition, the skin adhesive according to the present embodiment can be used to measure a biological component contained in the collected skin secretion. Here, the biological component is not particularly limited as long as it is a component of biological origin contained in skin secretions such as sweat, skin gas, sebum and the like. For example, water, saccharides such as glucose (glucose), decomposition products of saccharides such as lactic acid and salts thereof, sodium, potassium, calcium, magnesium, phosphorus, sulfur, iron, zinc, copper, inorganic salts such as chromium, amino acids, ammonia (Liquid), nitrogen containing substances such as urea, uric acid, creatinine, vitamins such as vitamin C and vitamin D, hormones, acetone, acetaldehyde, ammonia (gas), gas components such as methane, ethane, hydrogen, acetic acid, diacetyl Etc. may be mentioned, but not limited thereto. Furthermore, drugs such as sweat and skin gas, sebum, etc. are also used for drugs taken by the living body and metabolites of the drug, and chemicals such as toluene and benzene taken from the working environment and living environment, and metabolites of the chemicals. As long as it is contained and excreted in skin secretion, it shall be included as a biological component. The biological component is preferably glucose, which is an index for diagnosis and management of diabetes and the like, and lactic acid, which is an index of physical stress such as muscle fatigue and blood circulation failure.

  Measurement of biological components contained in skin secretions should be used as indicators of diagnosis and management of diseases such as diabetes, weight control, physical stress such as muscle fatigue or blood circulation failure, and mental stress it can. In addition, information on biokinetics such as metabolism of chemicals and drugs in the environment and drug management can also be provided. Thus, measurement of biological components contained in skin secretions can provide useful biological information.

  As explained above, the skin adhesive according to the present embodiment non-invasively, non-invasively and safely measures biological components contained in skin secretions such as sweat and skin gas secreted from the skin. Can be used to In addition, since the skin adhesive according to the present embodiment can absorb skin secretions from any area of the skin surface without leaking it at any arbitrary site on the skin surface, it is possible to measure the biological components contained in the skin secretions. It is possible to obtain reliable biological information.

(How to collect skin secretions)
The method for collecting skin secretions according to this embodiment adheres the skin adhesive according to the above-described embodiment to the skin surface, and absorbs skin secretions in the hydrogel layer contained in the skin adhesive. And collecting the skin secretions. Therefore, the method for collecting skin secretions according to this embodiment is to non-invasively, non-invasively and safely collect skin secretions secreted from the skin.

  The adhesion to the skin surface can be made by bringing the skin adhesive material according to this embodiment itself into adhesion performance, so that the skin surface is brought into light contact with the skin surface and lightly pressed if necessary. it can. As described above, the skin adhesive according to the present embodiment has flexibility and adheres to the skin surface of any area at any area on the skin surface. It can absorb skin secretions from the skin surface without leaking it. Therefore, it is possible to collect skin secretions such as trace amounts of sweat which are secreted at rest or in a short time.

  The adhesion time of the skin adhesive to the skin surface in the method for collecting the skin adhesive according to the present embodiment is not particularly limited, but the site of the skin from which the skin secretion is to be collected, the exercise state of the subject, the temperature It can set suitably according to external environments, such as humidity, etc. Preferably, it can be 1 to 15 minutes, particularly preferably 5 minutes or less, for example, about 1 to 5 minutes.

  The method for collecting skin secretions according to the present embodiment is capable of collecting skin secretions secreted from the skin locally. In addition, a skin adhesive can be continuously collected by sequentially reattaching the skin adhesive according to the present embodiment or by sticking a new skin adhesive at a shifted position. Therefore, according to the method of collecting skin secretions according to the present embodiment, it is possible to collect local continuous skin secretions, and is used for collection, measurement, etc. of skin secretions over time, such as before and after exercise. be able to.

  As explained above, the method for collecting skin secretions according to the present embodiment is to collect skin secretions such as sweat and skin gas that are secreted non-invasively, non-invasively and safely from the skin. it can. The method of collecting the skin secretion can absorb the skin secretion from the skin surface of any area without leaking at any arbitrary part of the skin surface by using the skin adhesive material according to the present embodiment, It is also suitable for collecting skin secretions. Furthermore, the method for collecting skin secretion can perform collection of local continuous skin secretion.

(Method of measuring biological components)
In the method of measuring a biological component according to the present embodiment, (i) the skin adhesive according to the above-described embodiment is adhered to the skin surface, and skin secretions are absorbed in the hydrogel layer contained in the skin adhesive. And (ii) eluting the biological component contained in the skin secretion absorbed in the hydrogel layer of the skin adhesive peeled off from the skin surface; Measuring the eluted biological component. Therefore, the method of measuring the biological component according to the present embodiment is to non-invasively, non-invasively and safely measure the biological component contained in the skin secretion secreted from the skin.

  Here, the biological component to be measured in the method of measuring the biological component according to the present embodiment is as described in the section of (skin adhesive material), and preferably becomes an index for diagnosis or management of diabetes etc. Glucose and lactic acid that is an indicator of physical stress such as muscle fatigue and blood circulation failure.

  The step (i) in the method of measuring a biological component according to the present embodiment is as described in the above-described method of collecting skin secretions.

  In the step (ii) in the method of measuring a biological component according to the present embodiment, elution of the skin secretion absorbed in the hydrogel layer can be performed by a method known in the art. The skin adhesive according to the present embodiment can be easily peeled off from the skin, for example, the hydrolizable layer of the skin adhesive that has absorbed the peeled skin secretion is immersed in a suitable solvent, and if necessary, stirred Skin secretions can be eluted from the hydrogel layer by shaking, sonication or the like. The hydrogel layer may be previously broken prior to elution.

  The skin adhesive according to the above-described embodiment used in the method for measuring a biological component according to the embodiment is composed of a hydrogel layer containing a hydrophilic polymer, water, and a polyhydric alcohol. Therefore, all components contained in the hydrogel layer are hydrophilic components, and in particular, polyhydric alcohols involved in adhesion of the skin surface and absorption of skin secretions etc. are hydrophilic components, so that the skin is easily secreted. The biological components contained in the substance can be eluted.

  As a suitable solvent to be used for elution, water, physiological saline, buffer solution, water-miscible organic solvent, water-immiscible organic solvent, mixed solvent of these, etc. can be used, and the living body to be measured is It can change suitably according to the kind of ingredient. The buffer is not particularly limited, and examples thereof include, but are not limited to, phosphate buffer, acetate buffer, borate buffer, Tris hydrochloric acid buffer, citrate buffer and the like. Examples of the water-miscible organic solvent include, but are not limited to, methanol, propanol, isopropanol, acetone, acetonitrile, tetrahydrofuran, dioxane, dimethylformamide, dimethylsulfoxide and the like. Non-water miscible organic solvents include, but are not limited to, dichloromethane, chloroform, diethyl ether, dibutyl ether, ethyl acetate and the like.

  During elution, solid-liquid separation treatment such as centrifugation or filtration to separate the eluate and the skin adhesive fragment according to this embodiment, dialysis treatment to remove salts, etc., labeling of biological components You may perform the labeling process etc. in order to do.

  Measurement of biological components in the eluate includes absorbance measurement, liquid chromatography (LC) such as high performance liquid chromatography (HPLC), liquid chromatography mass measurement (LC / MS), gas chromatography mass measurement (GC / MS) Etc., ion chromatography (IC), sensors and the like, and can be appropriately selected according to the type of biological component to be measured and the purpose of the measurement.

  At this time, the concentration of the biological component can be determined based on the obtained measurement value by creating a standard curve in advance using the biological component solution to be measured at the standard concentration within the target concentration range.

  The method for measuring a biological component according to the present embodiment is to locally collect skin secretions secreted from the skin and to measure it. In addition, a skin adhesive can be continuously collected and measured by sequentially replacing the skin adhesive according to the present embodiment or attaching a new skin adhesive. Therefore, the method of measuring the biological component according to the present embodiment can measure the biological component derived from the skin secretion continuously continuously, and measure the biological component derived from the skin secretion temporally such as before and after exercise etc. It can be used to

  As described above, the method of measuring a biological component according to the present embodiment is non-invasive, non-invasive, and safe for biological components contained in skin secretions such as sweat and skin gas secreted from the skin. Can be used to measure. In addition, the method of measuring the biological component can absorb absorbed skin secretion from any area of the skin surface without leaking it by using the skin adhesive according to the present embodiment. By measuring the biological component contained in the secretion, highly reliable biological information can be obtained. Furthermore, the method of measuring the biological component can measure the biological component in the local continuous skin secretion.

  Hereinafter, the present invention will be specifically described by way of examples. However, the present invention is not limited to these examples.

<Reference Example> Prior Art Conventional Technique for Collecting Skin Secretion Secreted from Skin As described in the above [Background Art] section, as a prior art technique for collecting skin secretions such as sweat, it is necessary to use a very small amount of finger Technology to collect sweat components by contacting them with 1% ethanol solution, etc., and technology to collect sweat that is stored within a predetermined time of 30 minutes or more by attaching parafilm, sweat absorption sheet, etc. to the skin Etc. have been reported. However, in the prior art, it is difficult to collect the very small amount of sweat (degree ² mg / cm 2/10 minutes or less) as at rest, also continuously sweat every few minutes even during exercise It is expected that it will be difficult to collect Table 1 below summarizes the academic information on sweat volume. However, the amount of sweating varies among individuals, and also varies depending on the measurement conditions such as temperature and humidity, the subject's characteristics such as the sex of the subject, the constitution and exercise intensity, etc. It is shown.

* Reference list Reference 1: Amano T et al., “Maximum rate of sweat resurfacing during exercise with regional differences, sex, and exercise training” European Journal of Applied Physiology (2017) 117: 1317-1327
Reference 2: Taylor NA et al., “Regional variations in transepidermal water loss, eccrine sweat gland density, sweat secretion rates and electrolytic composition in resting and exercising humans” “Extreme Physiology & Medicine 2013, 2: 4
Reference 3: Patterson MJ et al., "Variations in regional sweat composition in normal human males", Experimental Physiology (2000) 85 (6): 869-875.
Reference 4: Tsuruoka Noriko et al., "Development of a small size perspiration meter and measurement of perspiration under stress and thermal load", Biomedical Engineering, 54 (2016), No. 5, p. 207-217
Reference 5: Tomoko Fujimoto et al., "Primary topical hyperhidrosis medical care guidelines 2015 revised edition", Japanese Dermatological Association magazine, volume 125 (2015), number 7, p. 1379-1400

Example 1 Preparation of Skin Adhesive Material In this example, a preparation example of the skin adhesive material of the present invention is exemplarily shown.

(I) Skin adhesive (preparation)
The skin adhesive prepared here (skin contact area 1.0 cm ² or 1.5 cm ² , thickness 1.0 mm) weighs 0.13 mg / cm ² and absorbs 1 × phosphate buffered saline solution at 0.07 mg / cm ² (The weight before absorption was 0.13 mg / cm ² , and the weight after absorption was 0.21 mg / cm ² ). The skin adhesive material is acrylamide solution (30%: dissolved 29.2 g of acrylamide and 0.8 g of N, N'-methylenebisacrylamide dissolved in 100 ml of pure water), 5.0 ml of glycerol solution (80% w / v: dissolved in pure water) The mixture was prepared by mixing 9.7 ml and adding 0.15 ml of 10% ammonium persulfate as a polymerization initiator and 0.006 ml of tetramethylethylenediamine to polymerize.

(II) Skin adhesive (commercially available)
The commercial item which has a function equivalent to the skin adhesive material of said (I) can be utilized. For example, Technogel CR-H (Sekisui Plastics Co., Ltd., skin contact area 1.0 cm ² or 1.5 cm ² , thickness 0.6 mm) can be mentioned. The commercially available skin adhesive has a weight of 70 mg / cm ² and an absorption amount of 1 × phosphate buffered saline of 200 mg / cm ² (weight before absorption 70 mg / cm ² , weight after absorption is It was 270 mg / cm < ² >. Such a gel is, for example, 20% by mass of dimethylacrylamide, 0.046% by mass of methylenebisacrylamide, 65.9% by mass of polyglycerin, 13.254% by mass of water, and 0.5% by mass of a copolymer of acrylic acid and methacrylic acid It can be prepared by polymerizing / crosslinking a composition for polymerization containing 0.3% by mass of a photopolymerization initiator by light irradiation.

  The skin adhesive of the present invention includes a hydrogel layer, and the hydrogel layer is adhered to the skin, and skin secretions such as sweat and skin gas are absorbed in the hydrogel layer to collect skin secretions. Can be done (see Figure 1). Since the skin adhesive of the present invention has high skin adhesion, it can be collected without leaking skin secretions such as sweat which are secreted from the skin coated with the skin adhesive. Furthermore, since the hydrogel layer contained in the skin adhesive material of the present invention is a flexible material containing a large amount of water, it can be adhered to various parts of a living body, and skin secretions such as sweat can be collected. Also, the area of the skin surface to be collected can be controlled by the size of the hydrogel layer. The skin adhesive of the present invention can be easily peeled off and recovered from the skin, and skin secretions can be continuously collected by replacing a new skin adhesive or the like. In the following examples, the physical properties of the skin adhesive of the present invention are examined in detail.

<Example 2> Verification of Absorbent Performance of Skin Adhesive Material and Recovery Performance of Biological Component In this embodiment, the skin adhesive material of the present invention was verified with respect to the water absorption performance and the recovery performance of the biological component. In this example, the skin adhesive prepared in Example 1 was examined. Here, lactic acid was used as a biological component.

1. Water absorption amount (method)
With respect to the skin adhesive of the present invention prepared in Example 1, the water absorption performance was further verified. Specifically, the skin adhesive (n = 3) prepared in Example 1 above was used as a simulated sweat (phosphate buffered saline containing 5 mM L-lactic acid (1 × concentration, P5493 (SIGMA)) ) For 10 minutes. At this time, the contact area of each skin adhesive with the simulated sweat was 1.5 cm ² (1.0 cm × 1.5 cm), and the weight was 0.20 g, 0.21 g, 0.20 g. Then, the moisture of each skin adhesive was removed, and it put into a test tube, and the absorbed quantity (mg) of the simulated sweat absorbed by each skin adhesive was measured.

(result)
The results are summarized in Table 2 below. As a result, it was confirmed that the skin adhesive can absorb approximately 99 to 111 mg (66 to 74 mg / cm ² ) of simulated sweat and can efficiently absorb the simulated sweat. Thus, it can be understood that the skin absorbent of the present invention utilizing a hydrogel layer is a member suitable for collecting sweat and recovering biological components contained in the sweat.

2. Lactic acid recovery amount (method)
Subsequent to the above 1, the verification of the lactic acid recovery amount of the skin adhesive of the present invention is included in the simulated sweat collected by the skin adhesive for the skin adhesive of the present invention from which the simulated sweat was collected in 1 above. The concentration of lactic acid was measured. Specifically, 500 μL of phosphate buffered saline (1 × concentration, P5493 (SIGMA)) is placed in each test tube of the above 1 to soak each skin adhesive to dissolve lactic acid, and the lactic acid concentration of each elution solution Was measured with a lactate sensor, Lactate Pro.TM. 2 (ARKRAY). Furthermore, the obtained measured values were converted to the concentration when absorbed by the skin adhesive. Moreover, the lactic acid concentration was similarly measured also about the lactic acid solution itself (before contact with a skin adhesive) which was made to contact with a skin adhesive.

(result)
The results are summarized in Table 3 below. As a result, it was confirmed that the skin adhesive exhibits a good lactic acid recovery rate. It can be understood that the skin absorbent of the present invention utilizing a hydrogel layer is a member suitable for recovery of biological components such as lactic acid contained in sweat. Although the concentration of lactic acid in the simulated sweat before contact is about twice the value of the preparation value (100 mM) as measured by the lactic acid sensor (9.4 mM), it depends on the specification of the used lactic acid sensor It is.

<Example 3> Verification of absorption performance of skin adhesive and recovery performance of biological component-2
In the present example, the skin adhesive of the present invention for which excellent water absorption performance and biological component recovery performance were confirmed in Example 2 was verified by comparison with other absorbents. In this example, a commercial product which is considered to have the same function as that prepared in Example 1 as a skin adhesive was verified. Here, lactic acid was used as a biological component as in the second embodiment.

(Materials and methods)
The members examined in this example are as follows.
(II) Skin adhesive (Technogel CR-H (commercial item) of (II) in Example 1 above)
(III) Hydrocolloid bandage (Hydrocolloid bandage (Toyo Kagaku Co., Ltd.))
(IV) Silicone tape (Silicone tape non-woven fabric 192775EP-0 (3M Japan Co., Ltd.))
(V) Filter paper (filter paper 3φ 110, 1003-110 (Whatman))

In the same manner as in Example 2, each member of the above (I) to (V) was treated with a lactic acid solution (5 mM L-lactic acid, phosphate buffered saline (1 × concentration, P5493 (SIGMA): simulated sweat) It was allowed to stand on moistened filter paper for 10 minutes. At this time, the contact area of each member with the lactic acid solution was 1 cm ² (1 cm × 1 cm). Subsequently, the water on the surface of each member was removed, and the resultant was put in a test tube, and the absorbed amount (mg) of the lactic acid solution absorbed by each member was measured.

  Furthermore, 320 μL of phosphate buffered saline (1 × concentration, P5493 (SIGMA)) was placed in each test tube, and each member was immersed to elute lactic acid, and the concentration of lactic acid in each elution solution was measured using Measured with Pro.TM. 2 (Arcley). Moreover, the lactic acid concentration was similarly measured about the lactic acid solution itself (before contact with each member) made to contact each member.

(result)
The results are summarized in Table 4 below. As a result, the amount of absorption of the skin adhesive (II) was the highest, which was twice the amount of absorption of the filter paper (V). On the other hand, it was found that hydrocolloid bandages (III) and silicone tapes (IV) are not suitable as absorbents. Generally, in absorbent materials such as filter paper, the absorption limit of sweat is about 20 mg / cm ^2, but according to the skin adhesive (II) containing a hydrogel layer, it is about 3 of the conventional absorption limit It can be understood that it is possible to absorb twice as much water and it is possible to collect sweat for a long time. The skin absorbent material (II) also gave good results in terms of lactic acid recovery rate. From these results, it can be understood that the skin absorbent of the present invention utilizing a hydrogel layer is a member suitable for collecting sweat and recovering a biological component contained in the sweat. On the other hand, the hydrocolloid bandage (III) using a hydrophilic polymer as in the hydrogel was found to be unsuitable for either collection of sweat or recovery of biological components contained in the sweat. Hydrocolloid bandages are composed of a hydrophobic polymer in the adhesive component and a hydrophilic polymer in the absorbent component, so the absorption efficiency is poor, and the absorbed components are shielded by the hydrophobic polymer and eluted. It is thought that it is because it becomes difficult.

<Example 4> Verification of sweat absorption performance of skin adhesive material In this example, the skin adhesive material (commercial item) of the present invention which was found to have excellent water absorption performance in Example 2 is actually used The perspiration absorption performance was verified by adhering to the skin surface.

(Method)
The skin adhesive of the present invention was attached to the skin surface of a subject, and a treadmill (WELL ROAD 200E, Takei Instruments Industry Co., Ltd.) was used to collect sweat that was secreted during running exercise. Specifically, as shown in FIG. 2, the site of the fingertip, the left hand middle fingertip (1), the left hand medicine fingertip (2), the right hand medicine fingertip (3), the right hand middle fingertip (4) II) Apply the skin adhesive (Technogel CR-H, 8 mm x 8 mm) and immediately after low-intensity exercise (exercise load: running for 10 minutes at 9.0 km / hour, heart rate about 120 beats / minute) The amount of sweat absorbed by the skin adhesive was measured in 10 minutes.

(result)
The results are shown in FIG. As a result, absorption of sweat of 1.8 mg, 1.7 mg, 3.4 mg and 2.6 mg from the left middle finger tip (1), the left hand medicine finger tip (2), the right hand medicine finger tip (3) and the right hand middle finger tip (4) Was recognized. In terms of the units of the obtained absorption in mg / cm ^2/10 min, 2.8 mg / cm ^2/10 min, 2.7 mg / cm ^2/10 min, 5.3 mg / cm ^2/10 min, 4.1 mg / cm ^{It was} 2/10 minutes. Such absorption is secreted from the skin because it is consistent with the order and numerical academic information (4~23 mg / cm ^2/10 minutes) shown in the above reference example, the fingertip by the skin adhesive of the present invention It can be understood that it can be collected with high reproducibility. Although there is a difference in the amount of sweat between the left and right hands, this difference may be related to the dominant hand (the subject is right-handed).

<Example 5> Verification of measurement of biological components contained in sweat collected by skin adhesive material In this example, the skin adhesion of the present invention which was found to have excellent sweat absorbing performance in Example 4 Regarding the material, the measurement of the biological component contained in the sweat collected by the skin adhesive was verified. Here, lactic acid was used as a biological component.

(Method)
In Example 4, the concentration of lactic acid contained in the sweat collected by the skin adhesive was measured for the skin adhesive of the present invention from which the sweat was collected. Measurement of lactic acid concentration was carried out using Lactate pro (trademark) 2 used in Example 2. Specifically, in Example 4, the skin adhesive having absorbed four sweats from the fingertips is immersed in 200 μL of phosphate buffered saline (1 × concentration, P5493 (SIGMA)) and left for 1 hour while stirring. The biological components were eluted. Subsequently, the elution solution was dropped on a lactate pro (trademark) 2 sensor and measured.

(result)
The results are shown in FIG. As a result, the skin adhesive attached to the left middle finger tip (1), the left hand medicine finger tip (2), the right hand medicine finger tip (3), and the right hand middle finger tip (4) often produces 1.2 mM, 2.0 mM and 2.4 mM. , 1.6 mM lactic acid was detected. From these results, sweat can be collected by the skin adhesive of the present invention, and lactic acid, which is a biological component contained in the collected sweat, can be eluted from the skin adhesive and the concentration thereof can be measured. Can understand. Accordingly, it has been found that the skin adhesive of the present invention can be suitably used for the measurement of biological components contained in skin secretions such as sweat.

<Example 6> Verification of continuous absorption performance of sweat of skin adhesive material In this example, continuous absorption of sweat was obtained for the skin adhesive of the present invention which was found to have excellent sweat absorption performance in Example 4. The performance was verified.

(Method)
The skin adhesive of the present invention was attached to the skin surface of a subject, and a running exercise was carried out using a treadmill as in Example 4, and continuous collection of sweat secreted during exercise was performed. Specifically, the skin adhesive (Technogel CR-H, 8 mm × 8 mm) of the above-mentioned Example 1 is attached to the left middle finger tip of the fingertip for 10 minutes at rest before exercise. Low intensity exercise (exercise load: running at 9.0 km / hour, heart rate 120 beats / min) for 10 minutes, high intensity exercise (exercise load: running at 13.5 km / hour, 10 minutes immediately after such low intensity exercise, Sweat was collected for 10 minutes immediately after such high-intensity exercise for 10 minutes at a heart rate of about 160 beats / minute), and the amount of absorption of sweat by the skin adhesive was measured.

(result)
The results are shown in FIG. As a result, at rest before exercise, at low intensity exercise, immediately after low intensity exercise, at high intensity exercise, immediately after high intensity exercise, often, 2.5 mg, 9.0 mg, 1.8 mg, 10.7 mg, and 4.1 mg of sweat Absorption was observed. From these results, it can be understood that by using the skin adhesive material of the present invention, it is possible to continuously collect sweat secreted during exercise and after exercise. Therefore, it turned out that the skin adhesive of the present invention can be suitably used for collecting skin secretions such as sweat over time.

<Example 7> Verification of continuous measurement of biological components contained in sweat collected by skin adhesive In this example, it was confirmed that continuous collection of sweat was possible in Example 6. The continuous measurement of the biological component contained in the sweat extract | collected by the said skin adhesive was verified about the skin adhesive. Here, lactic acid was used as a biological component.

(Method)
In Example 6, the concentration of lactic acid contained in the collected sweat was measured for the skin adhesive of the present invention from which the sweat was collected. Measurement of lactic acid concentration was carried out using Lactate pro (trademark) 2 used in Example 2. Specifically, in Example 6, at the time of resting before exercise, at low intensity exercise, immediately after low intensity exercise, at high intensity exercise, immediately after high intensity exercise, the skin adhesive material which absorbed sweat, 200 μL of phosphate buffer The biological component was eluted by soaking in physiological saline (1 × concentration, P5493 (SIGMA)) and leaving it for 1 hour while stirring. Subsequently, the elution solution was dropped on a lactate pro (trademark) 2 sensor and measured.

(result)
The results are shown in FIG. From these results, the skin adhesive material from which sweat was collected at rest, before exercise, at low intensity exercise, immediately after exercise, at high intensity exercise, and immediately after exercise was often 1.6 mM, 3.7 mM, 2.0 mM, 2.8 mM, 1.3 mM lactic acid was detected. From these results, it is confirmed that the concentration of lactic acid in sweat during exercise rises about twice as much as the concentration of lactic acid in sweat when not exercising, and monitoring the increase in lactic acid level during exercise I was able to. Therefore, sweat can be continuously collected by the skin adhesive of the present invention, and lactic acid, which is a biological component contained in the collected sweat, is eluted from the skin adhesive and the concentration thereof is continuously measured. I can understand that I can do it. Accordingly, it has been found that the skin adhesive of the present invention can be suitably used for continuous measurement of biological components contained in skin secretions such as sweat.

<Example 8> Verification of continuous collection of sweat from a site other than the fingertip In this example, the skin adhesive material of the present invention confirmed to be capable of continuously collecting sweat secreted from the fingertip in Example 6 We examined the adaptation to the sweat that is secreted from the skin other than the fingertips.

(Method)
The skin adhesive of the present invention is applied to the skin surface of a subject, running as in Example 4 using a treadmill, and sweat excreted from various parts of the body during exercise under various exercise conditions. Continuous collection of Specifically, head: Forehead, arms: forearm and palm, legs: skin adhesive material (technogel CR-H, 0.8 cm × of (II) in Example 1 above at five places of thigh and lower leg) 0.8 cm) was applied, and the amount of sweat absorbed by the skin adhesive during 4 minutes of running under 4 kinds of exercise load conditions (0 km / hour, 10 km / hour, 12 km / hour, 14 km / hour) was measured.

(result)
The results are shown in Table 3 and FIG. Table 3 is a table summarizing the obtained numerical data, and FIG. 7 is a graph representing such numerical values. From these results, it is understood that the amount of sweat secreted from each part of the body is increased according to the intensity of exercise load, and thus the skin adhesive material of the present invention can collect sweat secreted from the whole body with high reproducibility. In addition, it can be understood that the amount of sweat secreted from the forehead most significantly increases depending on the exercise load, and that the amount of sweat secreted from the palm does not necessarily correlate with the exercise load. Therefore, it turned out that the skin adhesive of the present invention is suitable for collecting skin secretions such as sweat, thereby being able to provide various biological information.

<Example 9> Verification of measurement of biological components contained in sweat collected from a site other than a fingertip by a skin adhesive material In this example, in Example 8, collection of sweat is possible from each part of the body. With respect to the skin adhesive of the present invention confirmed, the measurement of the biological component contained in the sweat collected by the skin adhesive was verified. Here, lactic acid was used as a biological component.

  The skin adhesive of the present invention is applied to the skin surface of various parts of the subject's body, and a running exercise is carried out using a treadmill as in Example 4, and sweat collected during exercise is collected and collected. The concentration of lactic acid contained in sweat was measured. Measurement of lactic acid concentration was carried out using Lactate pro (trademark) 2 used in Example 2. Specifically, head: forehead, arm: forearm, leg: skin adhesive material (technogel CR-H, 1.0 cm × 1.5 cm of (II) of Example 1 above at four places of thigh and lower leg) The skin adhesive that absorbs sweat and absorbs sweat with the skin adhesive material in the running 4 minutes of 4 kinds of exercise load conditions (0km / hour, 10km / hour, 12km / hour, 14km / hour) The solution was immersed in 500 μl of phosphate buffered saline (1 × concentration, P5493 (SIGMA)) and allowed to stand for 1 hour with stirring to elute the biocomponents. Subsequently, the elution solution was dropped on a lactate pro (trademark) 2 sensor and measured.

  The results are shown in FIG. FIG. 8 is a graph verifying the correlation between the amount of lactic acid in sweat and the exercise load intensity. From these results, the amount of lactic acid in sweat increased in proportion to the exercise load, and a correlation was recognized between the two. Thereby, sweat can be collected by the skin adhesive of the present invention, lactic acid which is a biological component contained in the collected sweat is eluted from the skin adhesive, and reproducibly measured in correlation with exercise load. Can understand that

<Example 10> Verification of correlation with blood concentration of biological component concentration in sweat absorbed by skin adhesive material In this example, in Examples 4 to 9, sweat secreted from various parts of the body The skin adhesive of the present invention which has been confirmed to be able to continuously collect and to measure the biological components contained in the sweat, the concentration of the biological components in the sweat absorbed by the skin adhesive, and The correlation with blood concentration was examined. Here, lactic acid was used as a biological component.

(Method)
The skin adhesive of the present invention is applied to the skin surface of the lower leg of a subject, and running exercise is carried out using a treadmill as in Example 4, and sweat collected during exercise is collected, and the collected sweat is collected. The concentration of lactic acid contained was measured. Measurement of lactic acid concentration was carried out using Lactate pro (trademark) 2 used in Example 2. Specifically, the skin adhesive (Technogel CR-H, 1.0 cm × 1.5 cm) of Example 1 (II) is attached to the lower leg, and four kinds of exercise load conditions (0 km / hour, 10 km / hour) At 12 km / h and 14 km / h), the skin adhesive in the running 4 minutes absorbs sweat and absorbs the sweat, 500 μl of phosphate buffered saline (1 x concentration, P5493 (SIGMA) The biological components were eluted by soaking and stirring for 1 hour. Subsequently, the elution solution was dropped on a lactate pro (trademark) 2 sensor and measured. Immediately after exercise, blood was collected from the earlobe and the concentration of lactic acid contained in the blood was measured.

  The results are shown in FIG. FIG. 9 is a graph verifying the correlation between the amount of lactic acid in sweat and the concentration of lactic acid in the blood. Although not shown here, the amount of lactic acid in sweat increased in proportion to the exercise load as confirmed in Example 8. Then, as shown in FIG. 9, the concentration of lactic acid in blood increases in proportion to the amount of lactic acid in sweat, and a correlation is recognized between the two. Thereby, sweat can be collected by the skin adhesive of the present invention, and lactic acid, which is a biological component contained in the collected sweat, is eluted from the skin adhesive, and reproducibly measured with correlation with blood lactic acid concentration. You can understand that you can do it. Therefore, it turned out that the skin adhesive of the present invention is suitable for collecting skin secretions such as sweat, thereby being able to provide various biological information with high reliability. That is, the skin adhesive of the present invention is non-invasive and non-invasive, in correlation with blood concentration, of biological components contained in skin secretions such as sweat and skin gas secreted from the skin. It can be used to measure safely.

  The present invention can be used in the technical fields requiring collection of skin secretions such as sweat and measurement of biological components contained in the skin secretions, particularly in a wide range of fields such as medicine, pharmacy, physiology, etc. is there.

Claims (8)

  Collection of skin secretions comprising a hydrogel layer holding water and polyhydric alcohol in a three-dimensional structure of a hydrophilic polymer having crosslinks, wherein the hydrogel layer adheres to the skin surface and absorbs skin secretions Skin adhesive material.   The skin adhesive according to claim 1, wherein the hydrophilic polymer is a poly (meth) acrylamide polymer.   The skin adhesive according to claim 1, wherein the polyhydric alcohol is glycerol.   The skin adhesive according to any one of claims 1 to 3, which is for measuring a biological component contained in the skin secretion.   The skin adhesive according to claim 4, wherein the biological component is glucose or lactic acid.   A process of collecting the skin secretion by adhering the skin adhesive according to any one of claims 1 to 3 to the skin surface and absorbing the skin secretion in the hydrogel layer. , How to collect skin secretions. The process of collecting the skin secretion by adhering the skin adhesive according to any one of claims 1 to 3 to the skin surface and absorbing the skin secretion in the hydrogel layer;
And e. Eluting the biological component contained in the skin secretion absorbed in the hydrogel layer of the skin adhesive separated from the skin surface, and measuring the eluted biological component. How to measure The method for measuring a biological component according to claim 7, wherein the biological component is glucose or lactic acid.