JP2015175617A - Evaluation method for skin stimulation (itch) caused by pressure-sensitive adhesive tape for skin, or the like - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide, in an evaluation method for skin stimulation (itch) caused by a test substance including an adhesive tape or a patch which are applied to human skin, a method for totally and objectively evaluating the test substance, considering chemical stimulation and the like caused by adhesive components in addition to physical stimulation caused by the hardness or moisture vapor permeability of the tape.SOLUTION: A test substance is applied to the skin of a nonhuman animal, and an act of scratching of the animal caused thereby is measured. It is preferred that at least a part of hair on the skin of the nonhuman animal be removed. It is more preferred that the hair cycle of the skin whose hair is removed be in a resting stage.

Description

  The present invention relates to a method for quantifying skin irritation (itching) of adhesive tapes for skin such as adhesive bandages and patches applied to the skin, and external preparations.

Itching is a sensation that occurs on the skin and the like that causes a scratch reflex. Causes of itching are diverse, including irritation caused by chemical substances such as histamine, skin diseases such as atopic dermatitis and contact dermatitis, diseases and psychological factors such as obstructive jaundice and diabetes, and stress. Contact with a foreign substance such as an adhesive tape can be cited as one cause.
As a method for evaluating the skin irritation caused by such a foreign substance, Patent Document 1 discloses that a 180 ° angle constant speed peel strength test is performed after the adhesive surfaces of the adhesive material are bonded to each other, and the adhesive strength is used. A method for assessing skin irritation is disclosed. However, what is obtained by this evaluation method is skin irritation (pain) at the time of peeling from the skin due to the adhesive force of the patch, and there is a problem that skin irritation (itching) during application cannot be evaluated.

  Patent Document 2 discloses a method for evaluating skin irritation based on a tensile test of a patch and the thickness of the epidermis after the patch. However, although physical stimulation due to the hardness of the patch can be evaluated from the tensile test, it is difficult to evaluate physical stimulation and chemical stimulation including factors such as moisture permeability. In addition, a method of measuring the skin thickness from a tissue section of the skin after peeling the adhesive material and evaluating skin irritation during the application is disclosed, but the correlation between the skin thickness and itching is unknown, Although it is possible to evaluate some kind of stimulus, it is considered difficult to evaluate itching.

  In recent years, it has been reported that scratching, which is an index of itchiness, is induced by subcutaneous injection of compound 48/80 into a mouse as an evaluation method of itch (see Non-Patent Document 1). Discloses a method (scratch test) for screening an antipruritic substance by measuring the scratching behavior of an animal. In this way, the scratch test is an established method for evaluating skin irritation, especially itching, from the scratching behavior of animals, but it is often used to evaluate the antipruritic effect of external preparations, and the skin of adhesive bandages and patches themselves A method for objectively evaluating the stimulus was not known.

In general, as an evaluation of skin irritation of a patch, visual judgment is performed in a rabbit skin primary irritation test and a cumulative skin irritation test. However, the erythema of the skin after peeling of the patch is determined by a graded score according to the standard of Draize et al. (Non-Patent Document 2), which is not preferable for evaluating minor differences, and is also not preferable for erythema and itching. The correlation was also unknown.
The index of skin irritation of the patch can be evaluated by a sensory test by humans, but more objective evaluation is required. Moreover, although the amount of exfoliation can also be evaluated, the correlation with the itchiness during sticking is unknown. Furthermore, it can be said that a patch containing a drug has a problem in applying an unapproved preparation to a human for screening.

Japanese Patent No. 3407895 Japanese Patent No. 4197511 Japanese Patent No. 4437251

Kuraisi Y. et al., Eur. J. Pharmacol., 275, 229-233 (1995) Draize J. H., The Journal of pharmacology and experimental therapeutics, 1944, 82, p 377

  The present invention relates to a method for evaluating skin irritation (itching) of test substances including adhesive bandages and patches applied to human skin, in addition to physical irritation due to tape hardness and moisture permeability, and chemical irritation due to adhesive components. An object of the present invention is to provide a method capable of comprehensively and objectively evaluating the test substance.

  That is, the gist of the present invention is as follows.

[1] A method for evaluating itch caused by a test substance, which comprises applying the test substance to the skin of a non-human animal and measuring the scratching behavior of the animal caused by the test substance.
[2] It is characterized by removing at least a part of hair from the skin of a non-human animal, applying a test substance to the skin from which the hair has been removed, and measuring the scratching behavior of the animal caused thereby. To evaluate the itch caused by the test substance.
[3] The evaluation method according to [2], wherein the hair cycle of the skin from which the body hair has been removed is in a resting period.
[4] The evaluation method according to [1] to [3], wherein the non-human animal used for the evaluation is a mouse 45 to 90 days old.
[5] The evaluation method according to any one of [1] to [4], wherein the skin from which the body hair has been removed is a back part of a mouse, preferably the back part of the head side.
[6] The evaluation method according to any one of [1] to [5], wherein the test substance is an adhesive tape for human skin or an external preparation.
[7] The evaluation method according to any one of [1] to [5], wherein the adhesive tape for human skin is a patch or a patch (transdermal absorbent).
[8] The evaluation method according to any one of [1] to [6], wherein the human skin adhesive tape is a patch.
[9] The evaluation method according to any one of [1] to [8], wherein after the test substance is applied to the skin, the scratching behavior of the animal is measured for 5 to 60 minutes.

[10] A plurality of adhesive tapes for human skin having different base materials and / or adhesive components are prepared, and skin irritation (itching) of each of the adhesive tapes is performed by the method according to any one of [1] to [9]. ) And selecting an adhesive tape with a relatively low degree of skin irritation (itching).
[11] A non-human animal model for evaluation of skin irritation (itching), wherein at least a part of hair in a skin region in a resting period is removed in synchronization with a hair cycle.
[12] The non-human model animal according to [11], wherein the animal is a 45-90 day old mouse.
[13] The non-human model animal according to [12], wherein the region from which the hair is removed is the back of the mouse, preferably the back of the head.

By the method of the present invention, it is possible to evaluate skin irritation (itching) during the application of adhesive bandages and patches, etc., and in the case of animals with hair, using an animal in the rest period of the hair cycle, Even if the hair removal operation is performed several days ago, the hair does not grow until that day, and the hair removal operation on that day is not necessary, so that the stimulation until immediately before the sample application can be minimized. Therefore, only the skin irritation derived from the test substance can be reflected more accurately. In addition, since it is not a sensory test by humans but counts the number of scratching behaviors of animals, it is excellent in objectivity and quantitativeness, and can also evaluate patches containing unapproved drugs.
The method of the present invention can be used for screening from the viewpoint of skin irritation (itching) for the adhesive bandages, patches, and adhesives under design, and depending on the adhesive, if different adhesives are applied to the same substrate It is also possible to compare skin irritation.

It is the result of evaluating the skin irritation (itching) of tape A using the method of the present invention.

[Definition]
As used herein, the term “non-human animal” encompasses animals belonging to vertebrates, preferably mammals. In a further preferred embodiment, the non-human animal is a rodent. In particular, rodents include Mus (Mus) (eg, mice) or Ratius (eg, rats), or Oryctologus (eg, rabbits) or Golden Hamsters (eg, Mesocricetus) (eg, Hamster) may be selected. A particularly preferred non-human animal is a mouse or a rat from the viewpoint of availability and breeding ease and handling.

  As used herein, the term “hair cycle” means the hair growth cycle, (1) growth phase (period in which hair follicle cells repeat division and hair grows actively), (2) regression phase (Period in which hair growth weakens and hair follicles atrophy), and (3) rest period (period in which hair follicles are completely retracted and resting), in this order, refers to a period consisting of three periods. The hair cycle is repeated throughout life in many animals. In the present specification, the “resting phase” refers to a period when the stem cells of the hair follicle are resting without causing new proliferation or differentiation as described above.

  As used herein, the term “adhesive tape for human skin” refers to an adhesive tape or sheet in which a support and an adhesive are laminated and applicable to human skin. The adhesive tape for human skin includes “patch” and “patch”. The patch contains a drug intended to act systemically or locally in the adhesive, while the patch does not contain a drug. Specifically, the patch includes a poultice (aqueous), a plaster (non-aqueous), and the like. Examples of the adhesive material include, but are not limited to, surgical tape, wound dressing material (hydrocolloid material, urethane foam material, emergency adhesive bandage), dressing material, hydrogel material, taping tape, adhesive bandage, and puncture part protective material.

The term “external preparation” as used herein means a composition in a form that contains a drug and is usually applied to the skin, and various forms such as cream, ointment, liquid, foam (foam), and emulsion. Included, but excluding patches.

[Non-human animals used for evaluation]
The method of the present invention is characterized by evaluating skin irritation (itching) caused by a test substance using a non-human animal. The non-human animal is preferably an animal in which the hair cycle of a part of or the whole body is synchronized. This hair cycle is different for each hair in the case of a body part and a human, but it is known that the hair cycle of the whole body surface is generally synchronized in mice. The first quiescent period of the mouse hair cycle is very short, around 19-21 days after birth, but after that, through the growth and regression stages, the second quiescence period is long and is estimated to continue until around 40-90 days after birth. The Since the hair cycle is repeated for a lifetime, it is not limited to a specific period, but from the viewpoint of the length of the period and the synchronization of the hair cycle, it is preferable to use a mouse 45 to 90 days old, More preferably, the mouse is 45 to 75 days old, and most preferably, the mouse is 49 to 56 days old (7 to 8 weeks old). It should be noted that hairless rats and hairless mice in which hair does not grow on the whole body or hair on the whole body are also included in the “non-human animal”. In this case, it is possible to administer the test substance without considering the hair cycle, but preferably mice of 45 to 90 days after birth are used.

[Test substance to be evaluated]
The test substance to be subjected to the method of the present invention is not particularly limited, such as an adhesive tape for skin and an external preparation, and preferably includes an adhesive tape for human skin (patch, patch). Generally, a patch or a patch has a structure in which an adhesive layer is formed on one side of a support. Examples of the support that can be used include films such as vinyl chloride, polyethylene, and polypropylene; papers such as Japanese paper; non-woven fabric made of fibers such as polypropylene, polyurethane, and polyester; knitted fabric; The pressure-sensitive adhesive layer is provided on one side of the support and plays a role of removably fixing the patch to the skin. The pressure-sensitive adhesive layer contains at least one pressure-sensitive adhesive. Moreover, it may contain optional components such as a softener, a tackifier, a pH adjuster, a medicinal component, a filler, an antioxidant (antioxidant, antiseptic), a colorant, and a fragrance as necessary. .
Although it does not specifically limit as a medicinal ingredient, it is desirable not to contain antipruritic substances, such as an antihistamine, as a medicinal ingredient, since itching is judged by measuring the scratching behavior of a non-human animal. Other medicinal ingredients include autonomic nervous system agonists, somatic nervous system agonists, central nervous system agonists, sympathomimetic drugs, sympathetic blockers, parasympathomimetic drugs, parasympathetic blockers, local anesthetics, General anesthetics, smooth muscle agonists, smooth muscle relaxants, non-steroidal anti-inflammatory drugs, steroidal anti-inflammatory drugs, anti-asthmatic drugs, uterine contractors, analgesics / hypnotics, antidepressants, anti-gout drugs, anti-serotonin Drugs, cardiovascular drugs, cardiotonic drugs, antiarrhythmic drugs, antihyperlipidemic drugs, diuretics, respiratory system drugs, digestive system drugs, blood / hematopoietic organ drugs, skin / mucosal drugs, Examples include imidazole antifungal drugs, hormones, vitamins, anti-infective drugs, antineoplastic drugs, antidiabetic drugs, and antiemetics.
In order to protect the surface opposite to the support of the adhesive layer, the adhesive tape for skin is preferably laminated with release paper that has been subjected to a release treatment with silicone or the like, or a wound body.

Although the kind of adhesive which the said adhesive layer contains is not specifically limited, For example, a urethane type adhesive, an acrylic adhesive, a rubber-type adhesive, a silicone type adhesive etc. are mentioned.
As a urethane type adhesive, what consists of a urethane resin obtained by making a polyol and a polyisocyanate compound react is mentioned. Examples of the polyol include polyether polyol, polyester polyol, polycarbonate polyol, and polycaprolactone polyol. Examples of the polyisocyanate compound include diphenylmethane diisocyanate, tolylene diisocyanate, hexamethylene diisocyanate, and the like.

  Urethane adhesives are highly safe and are practically used as medical polymer materials. High moisture permeability, good adhesion to the skin, flexible, familiar, and low-irritant adhesive. Therefore, it is suitable for an application to be applied to a human body, and is suitable as an adhesive for a medical patch. Moreover, all of adhesiveness, safety, stability as a material, economy, etc. are satisfied.

  Examples of the acrylic pressure-sensitive adhesive include acrylic acid esters having an alkyl group having 4 to 12 carbon atoms such as butyl acrylate, isononyl acrylate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate, isooctyl acrylate, and n-octyl acrylate. Or homopolymers of methacrylic acid esters; these (meth) acrylic acid esters as the main component, and other monomers (meth) acrylic acid, styrene, vinyl acetate, vinylpyrrolidone, acrylamide, hydroxyethyl acrylate, hydroxypropyl acrylate And a copolymer obtained by copolymerization with at least one other copolymerizable monomer. The other monomer is usually used in the range of 2 to 50% by mass.

  Examples of the rubber-based pressure-sensitive adhesive include natural rubber, styrene-isoprene-styrene block copolymer, polyisobutylene, polybutene, polyisoprene, a rubber-like elastic body such as a mixture of two or more thereof, rosin-based resin, and terpene. And a tackifier such as a copoly resin, coumarone-indene resin, and petroleum resin. If necessary, the rubber-based pressure-sensitive adhesive can be added with softening agents such as liquid polybutene, liquid polyisobutylene and mineral oil; fillers such as titanium oxide and zinc oxide; antioxidants such as butylhydroxytoluene and the like. . Among these, those having a styrene-isoprene-styrene block copolymer as a main base are preferable from the viewpoint of adhesiveness.

Examples of the silicone pressure-sensitive adhesive include a mixture or partial condensate of silicone rubber and silicone resin. Examples of the silicone rubber include a high molecular weight linear polydiorganosiloxane having a silicon functional group such as a silanol group at both ends, and the silicone resin includes a monofunctional siloxane unit and a tetrafunctional siloxane unit, Examples thereof include polyorganosiloxanes having a branched or network structure having silicon functional groups such as silanol groups or trialkylsilyl groups in the molecule. More specifically, such a silicone rubber is a long-chain copolymer of polydimethylsiloxane, and the silicone resin is an MQ resin (M units ((CH ₃ ) ₃ SiO _1/2 ) and Q units). (Silicone resin having a three-dimensional structure made of (SiO ₂ )).

  The softening agent contained as an optional component in the pressure-sensitive adhesive layer can be added as necessary because it can reduce the elasticity of the pressure-sensitive adhesive to impart flexibility and improve the pressure-sensitive adhesiveness. Examples of the softener include mineral oils such as liquid paraffin, liquid isoparaffin, and naphthenic oil; vegetable oils such as olive oil and olive squalane; animal oils such as lanolin, turtle oil, and beeswax; and synthetic oils such as fatty acid triglyceride and silicone oil. .

  Since the tackifier can impart appropriate tackiness to the pressure-sensitive adhesive, it is added as necessary. Examples of the tackifier include natural rosin derivatives, coumarone-indene resins, terpene oligomers, aliphatic petroleum resins, alkyl-modified phenol resins, polyterpene resins, gum rosins, rosin esters, oily phenol resins, petroleum hydrocarbon resins, and the like. It is done.

  A pH adjuster is added as needed. For example, karaya gum, citric acid, phosphoric acid, sodium hydrogen phosphate, anhydrous sodium hydrogen phosphate, pectin, anhydrous citric acid, alkali metal hydroxide, organic acid buffer and the like. By using these pH adjusters, the pressure-sensitive adhesive layer can be adjusted to the pH of normal skin by adjusting to the pH of normal skin.

  Furthermore, the adhesive layer can contain, for example, antibacterial agents, anti-inflammatory analgesics, steroid agents, anesthetic agents, antifungal agents, vitamin agents and the like as medicinal ingredients. These drugs exert their effects systemically or locally by percutaneous absorption, or exert their effects locally on the affixed site, but may cause skin irritation and itching.

  Furthermore, the test substance used in the method of the present invention may be an external preparation such as an ointment. The form of the external preparation as the test substance is not particularly limited as long as it is a form of external preparation that is usually applied to the skin, such as cream, ointment, liquid, foam (foam), and emulsion. In addition, the said external preparation may be mix | blended with the pharmacologically acceptable carrier and additive normally used according to the form.

[Evaluation method of skin irritation (itchiness)]
The method for evaluating skin irritation (itching) according to the present invention is characterized in that, in the above-described non-human animal, a test substance is applied to the skin of the non-human animal, and the scratching behavior of the animal caused thereby is measured. To do. In another aspect, at least a part of the hair is removed from the skin of the non-human animal, the test substance is applied to the skin from which the hair has been removed, and the animal is scratched by the test substance. It is characterized by measuring behavior. In another embodiment, the animal is caused by removing at least a part of hair from the skin in which the hair cycle is at rest, applying the test substance to the skin from which the hair has been removed, and causing the animal It is characterized by measuring the scratching behavior. From the viewpoint that the hair cycle is synchronized with the skin of the entire body surface, the preferred non-human animal is a mouse, regardless of the type or sex, but at least certain skin region of the non-human animal has hair. It suffices if it is in the rest period of the cycle. Commercially available systematic ones such as ddY, C3H, BALB / c, ICR, and hairless mice can be used, but the genetic background and phenotype differ depending on the strain. It is necessary to pay attention to this point. When ICR mice that respond to intradermal administration of histamine are used, it is suitable for evaluation of stimuli caused by the production of histamine, but the cause of itching is not necessarily limited to histamine, Various strains of mice can be appropriately selected according to the test substance to be used, or can be evaluated using multiple strains of mice. In addition to histamine, prostaglandins, serotonin, interleukin 6, trypeptase and the like are known as itch mediators. Although these substances are thought to act on nerve endings present at the boundary between the skin epidermis and dermis, the method of the present invention is not limited to these peripheral itches, and since it uses animal individuals, It is thought that central itch such as physical factors and stress can be evaluated.

In one embodiment of the present invention, a typical evaluation procedure when using a mouse as a non-human animal is as follows.
(1) By the day before the test, at least a part of hair is removed from the back skin of a 45-90 day old mouse. In the case of a mouse, the skin area from which the hair is removed is preferably the back skin in order to distinguish it from grooming behavior, and more preferably the head side dorsal area from the viewpoint of the possible range for the mouse to scratch. . In addition, the head side back part refers to the area | region of the head side which equally divided the area | region of the back part of a mouse | mouth.
The method for removing body hair is not particularly limited, and for example, shaving, hair removal cream, or the like can be used. For shaving, a hair removal cream may be used after lightly cutting the hair with a hair clipper. A hair removal cream is preferred because it is less likely to damage the skin, but if the skin is not damaged, it may be shaved using a shaver. Hairless mice remove hair when necessary.

  Conventionally, even if the hair was shaved on the day before the test, the hair was stretched on the next day and the patch could not be pasted, so reshaving was necessary, causing the skin to be damaged just before the test. Therefore, even if the hair removal operation is performed several days before the test, the hair does not grow until the day, and the hair removal operation on the day is not necessary, so that the stimulation until immediately before the sample application can be suppressed to the minimum. It is possible to more accurately evaluate skin irritation (itching) caused by.

(2) On the day of the test, the test substance is applied to the skin area where the hair has been removed. In the case of an adhesive tape for skin, a patch is applied, and then the scratching behavior of the mouse at a predetermined time is measured.

(3) The evaluation method can be performed by measuring the scratching behavior of a mouse to which the treatment or test drug is not applied or not. As the index of the scratching behavior, the number of scratching behavior, the scratching behavior time, the change in the skin state due to the scratching, and the like can be used, but the number of scratching behavior is preferably used. The scratching behavior may be measured directly by visual observation, but it is preferable to record and measure in an unattended environment. For example, it is desirable to record and observe behavior using a video camera or the like using a cage whose upper direction that can be observed from above is open or transparent. In mouse behavior observation, it is preferable to measure scratching behavior after acclimatization to the observation environment in advance. The number of scratching actions is measured by taking a series of actions until the mouse lifts the hind limb, scratches the application range or hair removal range of the test substance, and lowers the foot on the floor. The measurement time is 30 minutes or more, preferably 30 to 120 minutes per animal. A method of comparing the number of scratching actions is preferable, but the present invention is not limited to this.

(4) Evaluation of skin irritation (itching) is performed, for example, by comparing measured values when the test substance is applied and not applied with respect to the number of scratches measured in the above method.
Specifically, skin irritation (itching) caused by the test substance occurs when the number of mouse scratches measured when the test substance is applied increases significantly when the test substance is not applied. It is judged that Note that the experimental results can be evaluated according to ordinary statistical processing. In order to understand the cause of skin irritation (itching), for example, when a patch containing a specific medicinal ingredient and a patch not containing it are prepared and applied as a test substance, scratching By comparing the measurement values of the number of times, it can be estimated whether the medicinal component causes skin irritation (itching).

[Screening method for adhesive tape for human skin]
The skin irritation (itching) evaluation method described above can be used as a screening method for an adhesive tape for human skin with less skin irritation (itching).
That is, the screening method of the present invention provides a plurality of human skin pressure-sensitive adhesive tapes having different base materials and / or pressure-sensitive adhesive components, and non-human animal skin from which body hair has been removed from a skin region in which the hair cycle is in a resting state. By applying the respective adhesive tape for human skin to the skin, and measuring the scratching behavior of the animal caused by the animal, the skin irritation (itching) of each of the adhesive tapes is evaluated, and the skin irritation (itching) is relatively detected. The adhesive tape having a small degree of) is selected.

  By this method, a high-quality adhesive tape for skin can be selected from the viewpoint of reducing skin irritation (itching) when applied to a human. In addition, it is not a sensory test by humans but counts the number of scratching behaviors of animals, so it is excellent in terms of objectivity and quantitativeness, and is excellent in terms of safety etc. in evaluating patches containing unapproved drugs. Yes.

[Model animal]
In a different aspect of the present invention, a non-human animal model for evaluation of skin irritation (itching) is provided, wherein at least a part of hair in the skin region in a resting period is removed in synchronization with the hair cycle Is done. The model animal of the present invention is not particularly limited as long as it is a non-human animal in which the hair cycle of a part or the whole of the body is synchronized, but from the viewpoint of ease of handling and commercial availability, A 45-90 day old mouse is preferred.

The region from which the hair is removed is not particularly limited as long as the hair cycle of the skin is synchronized, but the head-side back portion of the mouse is preferable from the viewpoint of the range that the mouse can scratch.
As described above, the method for removing body hair may be physical shaving with a hair clipper or a shaver, or a hair removal cream.
The hair removal skin model animal produced in this way can be a useful model animal for evaluating skin irritation (itching).

  The details of the present invention will be described below with reference to examples. The present invention is not limited to these examples.

[Example 1]
1 On the day before the test, the skin on the back of the head of male 7-week-old ICR mice was shaved with a hair clipper and a hair removal cream in a range of 3 × 3 cm.
2 On the test day, acclimatized for 1 hour in the test cage.
3 A 2 × 2 cm tape A (Acetate cloth coated with acrylic resin) was affixed to the shaved area, and video was taken unattended.
4 In order to prove that the scratching behavior caused by tape application was itch, naloxone / saline solution (2 mg / kg body weight) was subcutaneously administered to the caudal dorsal region 15 minutes before tape application.
5 The number of scratches for 1 hour after application was measured and used as an index of skin irritation (itching).

The results are shown in FIG. In FIG. 1, as a control when tape A was applied, 1 hour per mouse when tape A was not applied and when tape A was applied and naloxone or physiological saline was subcutaneously administered. The number of scratches is shown. Each experiment is performed using 4 mice, and shows the average value and standard error of the measured number of scratches.
Since the number of scratching actions is increased by applying the tape A, it is considered that the tape A has some kind of skin irritation. Since this scratching behavior was suppressed by the administration of naloxone, it was considered that the scratching behavior with tape A was due to itching.

Claims (13)

  A method for evaluating itch caused by a test substance, which comprises applying the test substance to the skin of a non-human animal and measuring the scratching behavior of the animal caused by the test substance.   Removing at least a part of hair from the skin of a non-human animal, applying a test substance to the skin from which the hair has been removed, and measuring the animal's scratching behavior caused by the test substance, Evaluation method of itch caused by test substance.   The evaluation method according to claim 2, wherein the hair cycle of the skin from which the body hair has been removed is in a resting period.   The evaluation method according to any one of claims 1 to 3, wherein the non-human animal used for the evaluation is a 45-90 day old mouse.   The evaluation method according to any one of claims 1 to 4, wherein the skin region from which the body hair has been removed is a back part of a mouse, preferably a head side back part.   The evaluation method according to claim 1, wherein the test substance is an adhesive tape for human skin or an external preparation.   The evaluation method according to claim 6, wherein the adhesive tape for human skin is a patch or a patch (transdermal absorbent).   The evaluation method according to claim 6 or 7, wherein the adhesive tape for human skin is a patch.   The evaluation method according to any one of claims 1 to 8, wherein the scratching behavior of the animal is measured for 5 to 60 minutes after the test substance is applied to the skin.   A plurality of human skin pressure-sensitive adhesive tapes having different base materials and / or pressure-sensitive adhesive components are prepared, and the stagnation of each pressure-sensitive adhesive tape is evaluated by the method according to any one of claims 1 to 9, and relative A method for screening an adhesive tape for human skin, which comprises selecting an adhesive tape with a low degree of itchiness.   A non-human animal model for evaluation of itching, wherein at least a part of hair in a skin region in a resting state is removed in synchronization with a hair cycle.   The non-human model animal according to claim 11, wherein the animal is a 45-90 day old mouse.   The non-human model animal according to claim 12, wherein the region from which the hair is removed is a cranial back of a mouse.

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