JP2016017912A - Eye stimulus evaluation method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a stimulus evaluation method which can evaluate and compare functional evaluation of sensibility stimulation with a number value, concretely, and can be used for a skin external preparation, especially, a stimulus evaluation method for objectively and concretely evaluating an eye stimulus property of a surfactant, because a stimulus evaluation method has to have high correlation with a functional evaluation value obtained from a human being.SOLUTION: A surfactant which can be used for a skin external preparation is analyzed by a taste sensor, and stimulation property is evaluated based on a value obtained by measurement.SELECTED DRAWING: None

Description

  The present invention relates to a method for evaluating eye irritation, and more specifically, to determine the sensory irritation intensity of a surfactant that can be used in a topical skin preparation easily and with good reproducibility without using an animal. The present invention relates to a novel method for evaluating eye irritation.

  Ingredients blended in cosmetics, pharmaceuticals, agricultural chemicals, etc. have been confirmed to have effects on human health, so acute toxicity, eye irritation, respiratory sensitization, skin sensitization, mutagenicity, carcinogenicity, Hazard information such as reproductive toxicity has been obtained through animal testing.

  Among these hazard information, in terms of eye irritation, those that were not originally developed for use on the eyes are in contact with the eyes when they accidentally enter the eyes due to accidents. In order to reduce the risk, it is necessary to have a high correlation with human sensory evaluation values.

  Conventionally, eye irritation has been determined by a dreze method using rabbit eyes and a human sensory test. The Draize method is a method in which a test substance is forcibly instilled into one eye of a white rabbit and observed and evaluated by degeneration of the cornea, damage of the iris, inflammation of the conjunctiva, and the like. However, the test results vary widely depending on the organization, and a high degree of skill is required for the judgment of the test. Therefore, it has been considered that the reliability of the test method itself is low.

  In addition, conducting animal experiments is contrary to recent animal welfare and management issues, and has received strong criticism from animal welfare organizations, and improvements have been desired.

  Therefore, other methods such as bovine keratotomy test method (BCOP), isolated chicken eyeball test method, rabbit cornea-derived cell line (SIRC cell) and human cervical cancer cell (HeRa cell) have been reported. However, both are evaluation methods using animal tissues, and it cannot be said that animal welfare problems have been completely solved.

  On the other hand, sensory tests by humans have also been performed, but it is very similar to the Draise method in that it is actually instilled and evaluated, and there is a possibility that it involves risks, and it is evaluated from the stage of raw material screening Considering this, the burden on the tester is a very large problem in that it is necessary to evaluate a huge number of raw materials.

  Therefore, research on alternative methods for animal experiments that do not use animal tissues or organs is also underway, and eye irritation determination methods using liposomes or lyotropic liquid crystals that are lipid bilayer vesicles (for example, Patent Documents 1 to 3). However, it is difficult to quantitatively evaluate the eye irritation intensity and the operation is not easy.

Japanese Patent Publication No. 07-001266 Japanese Patent No. 3301656 JP 2012-242155 A

  The above-described conventional method has been desired to be improved from the viewpoint of animal welfare. Further, in the case of human sensory testing, there is room for improvement in that it depends on the individuality of the human, depends on the physical condition of the human, and sometimes cannot be quantified.

  The present invention has been made to solve the above problems, and an object of the present invention is to provide an eye irritation evaluation method that is easy to operate and has reproducibility without performing animal-derived tests.

  As a result of intensive studies to achieve the above-mentioned object, the present inventors can evaluate eye irritation without using animal tissue, and can provide a novel eye irritation that can be an alternative test method for the Draise method. As a sex assessment method, the inventors have found that a taste sensing system using a molecular film used in the taste measurement of foods has been found, and have achieved the present invention.

  That is, the present invention provides an irritation evaluation method characterized by evaluating the eye irritation of a surfactant that can be used in a skin external preparation based on a value measured by a taste sensor.

  The eye irritation evaluation method of the present invention is a novel eye irritation evaluation method that can be evaluated by a simple operation without using animal tissue, and can be an alternative test method for the Draise method.

Hereinafter, the present invention will be described in detail.
The taste sensor according to the present invention is made by imitating a human taste detection system, and measures and evaluates the response to a basic substance of taste to a sensor using a lipid membrane.
Depending on the type of lipid membrane used in the sensor of the taste sensor, taste detection is performed by responsiveness to basic tastes such as sourness, saltiness, sweetness, bitterness, umami, etc., even when multiple taste basic substances are mixed, It can be categorized according to the characteristics of responsiveness to the sensor.

  The sensor membrane is affixed to the sensor surface, and when these sensor membranes are immersed in the sample solution, the membrane potential of the lipid membrane changes. By processing this amount of change as a sensor output value, the taste of the measurement sample can be comprehensively determined.

In the measurement, when the sensor is first immersed in a reference solution to obtain the membrane potential Vr, and then the sensor is immersed in the sample solution, the membrane potential Vs changed by the interaction with the taste substance can be obtained. From this difference (Vs−Vr), a relative value of the sensor output corresponding to the taste is calculated.
The aftertaste can be obtained from this change in membrane potential (Vr′−Vr) by measuring the tip before washing the sensor with a reference solution and then immersing it again in the reference solution to obtain the membrane potential Vr ′. it can.
The first taste here is the taste of the moment when food is put in the mouth, and the aftertaste can be regarded as the taste that spreads in the mouth when the food is swallowed. In this evaluation method, the first taste can be reflected as pain immediately after the topical skin preparation enters the eye, and the after taste can be reflected in the persistence of the pain.

Sensors that can be used in this evaluation method include basic acidity, saltiness, sweetness, bitterness, umami, and astringency, but because the response of the sensor differs depending on the characteristics of the substance being evaluated, a sensor with a high output value Can be used for determination, and a bitterness and / or astringency sensor is particularly preferable.
Further, not only the sensor output value of the above-mentioned taste but also the sensor output value obtained as the aftertaste can be used for evaluation of stimulation and / or persistence of stimulation.
The presence and / or intensity of irritation can be determined from the sensor output value thus obtained.

Specifically, if the bitterness sensor and / or astringency sensor value measured by the taste sensor has a difference of 1 or more compared to a reference substance that is not eye irritant, Judgment can be made.
Further, when the value of the bitterness sensor and / or the astringency sensor measured by the taste sensor is 10 or more, it can be determined that intense pain is felt.
The apparatus is not particularly limited as long as these can be measured. For example, a taste recognition apparatus SA402B manufactured by Intelligent Sensor Technology can be used.

  In this evaluation method, the surfactant that can be used for the external preparation for skin is not particularly limited as long as it can be used for a taste sensor, and is a nonionic surfactant or anion generally used for external preparations for skin. Surfactants, cationic surfactants, amphoteric surfactants, and the like, preferably soluble or dispersible in water, or solubilized using polyhydric alcohol or polyhydric alcohol fatty acid ester, Nonionic surfactants that can be emulsified and dispersed are listed.

  Nonionic surfactants include glycerin fatty acid ester surfactants, sorbitan fatty acid ester surfactants, propylene glycol fatty acid ester surfactants, sucrose fatty acid ester surfactants, glycerin alkyl ether surfactants. , Polyoxyethylene alkyl ether surfactants, polyoxyethylene alkyl phenyl ether surfactants, and the like.

  Specific examples of the nonionic surfactant include, for example, polyglycerin polycapri such as glycerin monocaprylate, polyglycerin monocaprylate, polyglycerin sesquicaprylate, polyglycerin dicaprylate, polyglycerin tricaprylate. Rate, glycerin monocaprate, polyglycerin monocaprate, polyglycerin sesquica plate, polyglycerin dicaprate, polyglycerin polycaprate, etc., glycerin monolaurate, polyglycerin monolaurate, polyglycerin sesquilau Polyglycerin polylaurates such as rate, polyglycerol dilaurate, polyglycerol trilaurate, glycerol monomyristate, polyglycerol monomyristate, poly Polyglycerin polymyristates such as glycerin sesquimyristate, polyglycerin dimyristate, polyglycerin trimyristate, polyglycerols such as glycerin monopalmitate, polyglycerin monopalmitate, polyglycerin sesquipalmitate, polyglycerin dipalmitate Glycerol polypalmitates, glycerin monooleate, polyglycerin monooleate, polyglycerin sesquioleate, polyglycerin dioleate, polyglycerin trioleate and other polyglycerin polyoleates, glycerin monostearate, polyglycerin monostearate, polyglycerin Polyglycerol polystearates such as sesquistearate and polyglycerol distearate, glycerol monoisostearate, polyglycerol mono Glycerin polyglycerol fatty acid esters typified by polyglycerol polyisostearates such as sostearate, polyglycerol sesquiisostearate, polyglycerol diisostearate, sorbitan monocaprylate, sorbitan sesquicaprylate, sorbitan monocaprate, sorbitan Sesquica plate, sorbitan monolaurate, sorbitan sesquilaurate, sorbitan monooleate, sorbitan sesquioleate, sorbitan diolate, sorbitan trioleate, sorbitan monostearate, sorbitan distearate, sorbitan monoisostearate, sorbitan diisostearate Sorbitan fatty acid esters such as sorbitan triisostearate, propylene glycol monocaprylate, propylene -Glycol monocaprate, propylene glycol monolaurate, propylene glycol fatty acid esters such as propylene glycol monooleate, glycerin alkyl ethers such as polyglycerin capryl ether, polyglycerin lauryl ether, polyoxyethylene (hereinafter referred to as POE)- POE-sorbitan fatty acid esters such as sorbitan monolaurate, POE-sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan tetraoleate, POE-sorbitol monolaurate, POE-sorbite monooleate, POE-sorbite penta POE sorbite fatty acid esters such as oleate, POE-sorbite monostearate, POE-glycerin monoisostearate, POE POE-glycerin fatty acid esters such as glycerin triisostearate, POE-distearate, POE-monodiolate, POE-fatty acid esters such as ethylene glycol distearate, POE-lauryl ether, POE-oleyl ether, POE-stearyl ether, POE -Behenyl ether, POE-2-octyldodecyl ether and other POE-alkyl ethers, Pluronic types, POE / POP-alkyl ethers, sucrose fatty acid esters, etc. Among them, glycerin fatty acid ester surfactants and the like / Or excellent in evaluation of glycerin alkyl ether surfactants.

  Examples of the anionic surfactant include fatty acid soaps such as sodium laurate and sodium palmitate, higher alkyl sulfates such as sodium lauryl sulfate and potassium lauryl sulfate, and alkyl ether sulfates such as POE-sodium lauryl sulfate. And N-acyl sarcosine acids such as sodium lauroyl sarcosine, alkylbenzene sulfonates such as sodium lauroyl sarcosine, and amino acid surfactants such as sodium N-lauroyl glutamate.

  Examples of the cationic surfactant include alkyltrimethylammonium salts such as lauryltrimethylammonium chloride, alkyl quaternary ammonium salts, alkyldimethylbenzylammonium salts, and benzalkonium chloride.

  Examples of amphoteric surfactants include imidazoline-based amphoteric surfactants and betaine-based surfactants.

Furthermore, alcohol etc. can also be added to this evaluation method as needed.
For example, the solubility of the surfactant that can be used in the external preparation for skin can be improved by adding the above-described alcohol or the like.
EXAMPLES Next, although an Example is given and this invention is demonstrated in more detail, this invention is not restrict | limited to these Examples at all.

  In this example, the following raw materials were adjusted to a concentration of 0.5% by weight by a conventional method and measured with a taste sensor. Then, sensory evaluation of eye irritation was performed using the surfactant solution used for the analysis. However, since it is suggested that the surfactant having a sensor output value of more than 10 has very strong eye irritation, sensory evaluation was performed using a surfactant solution having a concentration of 0.1% by weight.

(sensory evaluation)
The sensory evaluation was performed by a panel of five people to instill 0.05 ml of solution and evaluate the presence and / or strength of irritation.
The evaluation criteria are as follows.
++++: Feeling intense pain ++: Feeling pain ＋: Feeling uncomfortable −: Feeling neither pain nor discomfort

  Table 1 shows the measurement results and sensory evaluation results of the taste sensor for each type of raw material that can be used in the external preparation for skin.

  As is apparent from the results shown in Table 1, if the sensor output value of the raw material that can be used for the external preparation for skin is high, it is a result that the sensory evaluation feels strong stimulation, and the irritation is evaluated by the evaluation method of the present invention. There was a high correlation between sensory evaluation results and sensory evaluation by humans, confirming the possibility of a new eye irritation evaluation method.

  Next, Table 2 shows the measurement results and sensory evaluation results of the taste sensor in the raw materials having similar structures among the raw materials that can be used for the external preparation for skin.

  As is apparent from the results shown in Table 2, among the raw materials that can be used for the external preparation for skin, even a raw material having a similar structure can detect a slight difference in irritation according to this evaluation method. The value was confirmed to be highly correlated with sensory evaluation.

  Table 3 shows the measurement results and sensory evaluation results of various other raw material taste sensors that can be used for the external preparation for skin.

  As is apparent from the results shown in Table 3, by using this evaluation method, the eye irritation of various raw materials that can be used in the external preparation for skin can be analyzed with a taste sensor, and the output value of the analyzed sensor Was highly correlated with sensory evaluation.

  Although not restricted in the present invention, it has been found that the eye irritation of the raw material that can be used for the topical skin preparation at this stage appears to the bitter taste sensor and / or the astringency sensor of the taste sensor. It is clear that the reactivity to the sensor differs depending on the raw material species.

  By using the evaluation method of the present invention, the sensory evaluation of sensory stimulation that has been relied on by humans can be compared and evaluated more specifically by numerical values. In other words, it is possible to objectively and easily perform eye irritation evaluation that relies on the sensation conventionally performed by humans and animals, which contributes greatly to industrial contribution.

Claims (3)

  An eye irritation evaluation method comprising evaluating the eye irritation of a surfactant based on a value measured by a taste sensor.   2. The eye irritation evaluation method according to claim 1, wherein the value measured by the taste sensor is a value of a bitter taste sensor and / or an astringency sensor.   The method for evaluating eye irritation according to claim 1 or 2, wherein the surfactant is a nonionic surfactant.