Agents for improving wrinkles and sagging skin and a simple screening method therefor

Abstract

To provide a skin wrinkle / looseness improvement agent based on physical action, which can exhibit wrinkle / looseness improvement effect at a level and within a period satisfactory to a user and can prevent application of mental and physical stress even if used for a long time and / or repeatedly, and a simple screening method thereof, and to provide a film for simple screening of the skin wrinkle / looseness improvement agent based on physical action.SOLUTION: A response to an elongation stimulus of a skin declined in suppression of deformation or recovery function from deformation is reproduced by a film which serves as a skin alternative, and a skin wrinkle / looseness improvement agent based on physical action is easily screened by measuring a change in physical property caused by coating of the film with a blank to be tested.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to an agent for improving wrinkles and sagging skin by adjusting the physical properties of the skin through physical action, and a simple method for screening for the agent. The present invention also relates to a membrane for the screening. [Background technology]

[0002] Since wrinkles and sagging skin have a significant impact on first impressions, there are high expectations for prevention and improvement, and there is a strong desire for a highly effective agent for improving wrinkles and sagging skin.

[0003] Traditionally, wrinkles and sagging skin have been thought to be primarily caused by a decrease or degeneration of dermal extracellular matrix components and a decrease in subcutaneous fat due to aging and ultraviolet rays, and topical skin preparations intended to improve these conditions have attempted to regulate physiological functions, such as promoting the production of target components by targeting the cells responsible for producing each of the target components, or controlling the activity of related enzymes (Patent Documents 1, 2, and 3). However, it is not easy to restore physiological functions that have deteriorated due to aging and ultraviolet rays, and it has been difficult to say that wrinkles and sagging have been improved to a level or for a period of time that satisfies users.

[0004] On the other hand, methods have also been proposed that form a film on the skin immediately after application, providing an immediate firmness and anti-wrinkle effect (Patent Documents 4, 5, and 6). These methods rely on the physical action of the composition or cosmetic, regardless of the state of the user's physiological functions, and therefore users were highly satisfied with the improvement effect on wrinkles and sagging.

[0005] To achieve the above-described method, methods for evaluating whether a test material has desired physical properties, such as elasticity, include a method in which an aqueous solution of an anti-wrinkle composition is applied to a test participant to measure the anti-wrinkle effect, and a method in which the test participant evaluates the degree of wrinkles and firmness (Patent Documents 4 and 6). However, because evaluations by multiple test participants are required for each test material, a simpler method is needed for screening a large number of test materials with different test materials, formulations, and preparation methods. As a method that does not require test participants, a method has been proposed in which a cosmetic is applied to a transparent solid, the area ratio of the formed film before and after drying is calculated, and the film shrinkage rate is used as an index to evaluate the firmness of the cosmetic (Patent Document 5). However, this method only evaluates the physical properties of the cosmetic and does not take into account the effect on the skin when actually applied. Therefore, there have been cases in which cosmetics that cannot maintain firmness when stretched by blinking or changes in facial expression are applied, or cosmetics that shrink too much, causing discomfort to the user, have been selected. As described above, it has been difficult to select an agent for improving wrinkles and sagging skin that has an effect of improving wrinkles and sagging skin to a level and for a period that satisfies the user, and that does not cause stress to the user's mind and body even when used for a long period of time and / or repeatedly. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Patent application 2019-548953 [Patent Document 2] Patent application 2016-238137 [Patent Document 3] Patent application 2005-341449 [Patent Document 4] Patent application 2013-110159 [Patent Document 5] Patent application 2019-539644 [Patent Document 6] Patent application No. 10-250476 Summary of the Invention [Problem to be solved by the invention]

[0007] An object of the present invention is to provide a skin wrinkle and sagging improvement agent that acts on the skin through a physical action, which can be expected to improve wrinkles and sagging at a level and for a period of time that satisfies the user, and which does not cause physical or mental stress even with long-term and / or repeated use, and a simple method for screening such an agent.Another object of the present invention is to provide a membrane for simple screening of skin wrinkle and sagging improvement agents that act on the skin through a physical action. [Means for solving the problem]

[0008] The inventors believed that if they could reproduce the response of skin with impaired recovery from deformation to stretching stimuli using a skin substitute and measure the changes in the physical properties of the skin substitute caused by applying a test material to the skin substitute, it would be possible to easily screen for agents that improve skin wrinkles and sagging through physical actions. Based on this idea, the inventors established a method for screening membranes that can be used as skin substitutes and agents that improve skin wrinkles and sagging using such membranes. They confirmed that agents that improve skin's recovery from deformation selected by this screening method have the desired effects, thereby completing the present invention. This invention makes it possible to select, from among many test materials, an agent that can be expected to improve wrinkles and sagging at a level and for a period that satisfies the user, and that also does not cause physical or mental stress even with long-term and / or repeated use. [1] The first invention is a method for screening an agent for improving wrinkles and sagging skin, comprising the following steps: (1) A process in which both ends of a film are held in the sample grip of a viscoelasticity measuring device and stretched, and the load when the elongation strain is 2 is 3N or more and 12N or less, and the yield point is in the range of elongation strain 0.5 or more and 4 or less, and the test material is applied to the film. (2) A process in which both ends of the film are held by the sample gripper of the viscoelasticity measuring device and stretched to the extent that an elongation strain occurs that exceeds the yield point, and then the movement of the sample gripper is stopped to maintain the elongation strain. (3) A process for measuring the load change in the process (2). (4) A step of selecting a test material that reduces the rate of load decrease immediately after the movement of the sample gripper is stopped when comparing a film coated with the test material with a film without any coating, as an agent for improving skin wrinkles and sagging. [2] The second invention is a method for screening an agent for improving skin wrinkles and sagging, comprising the following steps: (1) A process in which both ends of a film are held in the sample grip of a viscoelasticity measuring device and stretched, and the load when the elongation strain is 2 is 3N or more and 12N or less, and the yield point is in the range of elongation strain 0.5 or more and 4 or less, and the test material is applied to the film. (2) A process in which both ends of the film are held by the sample gripper of the viscoelasticity measuring device and stretched to the extent that an elongation strain occurs that exceeds the yield point, and then the movement of the sample gripper is stopped to maintain the elongation strain. (3) A process for measuring the load change in the process (2). (4) A step of selecting a test material as an agent for improving skin wrinkles and sagging, in which the maximum load observed in (3) does not increase when the test material is applied to a film compared with a film without any application, and the rate of decrease in the load immediately after the movement of the sample gripper is stopped decreases when the test material is applied to a film with no application. [3] The third invention is a method for screening an agent for improving skin wrinkles and sagging, comprising the following steps: (1) A process in which both ends of a film are held in the sample grip of a viscoelasticity measuring device and stretched, and the load when the elongation strain is 2 is 3N or more and 12N or less, and the yield point is in the range of elongation strain 0.5 or more and 4 or less, and the test material is applied to the film. (2) A process in which both ends of the film are held by the sample gripper of the viscoelasticity measuring device and stretched to the extent that an elongation strain occurs that exceeds the yield point, and then the movement of the sample gripper is stopped to maintain the elongation strain. (3) A process for measuring the load change in the process (2). (4) A step of selecting a test material as an agent for improving skin wrinkles and sagging, in which the elastic modulus calculated from the measurement in (3) does not increase when the test material is applied to a film compared with a film to which nothing is applied, and the rate of decrease in the load immediately after the movement of the sample gripper is stopped decreases when the test material is applied to a film to which nothing is applied. [4] A fourth invention is a method for screening an agent for improving skin wrinkles and sagging according to any one of the first to third inventions, wherein the surface of the film is hydrophilic. [5] A fifth invention is a membrane used in the method for screening an agent for improving skin wrinkles and sagging according to any one of the first to fourth inventions. [6] The sixth invention is an agent for improving wrinkles and sagging skin selected by the screening method according to any one of the first to fourth inventions. [7] The seventh invention is a skin external preparation characterized by containing the skin wrinkle and sagging improvement agent according to the sixth invention. [Effects of the Invention]

[0009] The present invention provides a skin wrinkle and sagging improvement agent that acts through a physical action, which can be expected to improve wrinkles and sagging at a level and for a period of time that satisfies the user, and which does not cause physical or mental stress even with prolonged and / or repeated use, as well as a simple screening method for the agent. The present invention also provides a membrane for simple screening of skin wrinkle and sagging improvement agents that act through a physical action. Furthermore, in light of recent research (Patent Application Nos. 2020-061921 and 2018-068271), skin wrinkle and sagging improvement agents that are suitable for prolonged and / or repeated use, selected by the screening method of the present invention, can be used for prolonged and / or repeated use, and therefore have an immediate anti-wrinkle and anti-sagging effect as well as an effect of improving wrinkles and sagging over time. [Brief explanation of the drawings]

[0010] [Figure 1] Conceptual diagram of the process of stretching a film by holding both ends of the film in the sample gripper of the viscoelasticity measuring device [Figure 2] Load-strain curve conceptual diagram [Figure 3] Example of measured values ​​of membrane load-time curve [Figure 4] Load-time curve examples for membranes coated with useful test materials and uncoated membranes [Figure 5] Scatter plot of maximum load and load decrease rate for films coated with test materials [Figure 6] Immediate anti-wrinkle effect of the skin wrinkle and sagging improvement agent of the present invention [Figure 7] Anti-wrinkle effect over time of the skin wrinkle and sagging improvement agent of the present invention [Figure 8] Scatter plot of elastic modulus and load reduction rate of the film coated with the test material DETAILED DESCRIPTION OF THE INVENTION

[0011] The present invention relates to a method for easily screening for agents for improving skin wrinkles and sagging through physical actions, using a skin substitute to reproduce the response to stretching stimuli of skin with impaired skin deformation suppression and recovery function from deformation, applying a test material to the skin substitute, and measuring the changes in the physical properties of the skin substitute. This screening method involves using a membrane as the skin substitute and applying the test material to it; holding both ends of the membrane in the sample gripper of a viscoelasticity measuring device and stretching it to a degree that generates an elongational strain exceeding the yield point, then stopping the movement of the sample gripper to maintain the elongational strain; and measuring the load while maintaining the elongational strain after stretching. The load change is measured during these processes, and a test material that exhibits a reduced rate of load decrease immediately after the movement of the sample gripper is stopped when the membrane coated with the test material is compared to a membrane without any coating is selected as an agent for improving skin wrinkles and sagging. The inhibition of skin deformation and the response to stretching stimuli of the skin refer to responses that can be understood solely as physical responses. Therefore, the skin substitute used to measure changes in physical properties resulting from the application of a test material is not limited in any way to its constituent components, as long as it can mimic the physical properties of skin. Therefore, the film used in this application need only be able to reproduce the physical properties of skin, and does not necessarily have to be similar to the constituent components of skin. Furthermore, the term "nothing applied" in this invention includes both cases where nothing is applied and cases where a control substance, such as a solvent, is applied to evaluate the performance of the test material. Figure 1 shows a conceptual diagram of the process of holding both ends of a film in the sample holder of a viscoelasticity measuring device and stretching it, and Figure 2 shows a conceptual diagram of the load-extension strain curve measured as a change in load.

[0012] In the present invention, stretching to generate elongational strain in a membrane can be performed, for example, by holding both ends of the membrane in the sample gripping section of a membrane viscoelasticity measuring device as shown in Figure 1 and applying a tensile load by moving the sample gripping section. The two ends of the membrane here refer to the sections on both sides of the membrane, with the distance between the sample gripping sections being the length to be loaded, and with an area large enough to secure the membrane so that it does not move when stretched. The stretching speed is not particularly limited, as long as the membrane coated with the test material (which serves as a comparison) is stretched at the same specific speed conditions as the uncoated membrane. The stretching speed may be constant or may vary.

[0013] The extension strain of the present invention is a value ε expressed by the following equation (1) when the length of the membrane to which the load is applied before extension is L(0) and the length of the membrane to which the load is applied after extension is L.

[0014]

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[0015] The load in this invention refers to the magnitude of the force applied to the sample gripper, measured in units of N (Newton). The force sensed by the sample gripper during stretching, i.e., the force applied in the stretching direction, is called the tensile load. When the load is F and the cross-sectional area of ​​the membrane perpendicular to the stretching direction is A, the tensile stress of the membrane is the value σ expressed by Equation 2.

[0016]

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[0017] The elastic modulus of the film is the value E expressed by [Equation 3].

[0018]

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[0019] Therefore, the load F is expressed by [Equation 4].

[0020]

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[0021] As shown in Figure 2, the yield point of the present invention is the limit point at which a membrane will no longer return to its pre-stretched shape when a tensile load is applied to the membrane and the elongation strain increases, and membranes can be used whose elongation strain at the yield point is in the range of 0.5 to 4. With membranes that reach their yield point at an elongation strain less than 0.5 or more than 4, even if a test material that can adjust the physical properties of the membrane is found, it may not exhibit an effect sufficient to adjust the physical properties of the skin, or an agent for improving wrinkles and sagging skin that can adjust the physical properties of the skin may be overlooked.

[0022] In the present invention, both ends of the membrane are held in the sample gripping parts of the viscoelasticity measuring device and stretched to an extent that generates an elongational strain exceeding the yield point of the membrane, but the degree of stretching is within a range that does not cause the membrane to break and exceeds the yield point, preferably an elongational strain of up to 4. If the subsequent steps are carried out in a state where the membrane is stretched to an elongational strain greater than 4, the physical properties of the membrane cannot be changed unless a tensile stress greater than that required to improve wrinkles and sagging skin is applied, and therefore an agent for improving wrinkles and sagging skin that can adjust the physical properties of the skin may be overlooked.

[0023] In the present invention, a film can be used that can be stretched without breaking and has a load of 3N or more and 12N or less when the elongation strain reaches 2. A film that breaks when the elongation strain is less than 2 cannot be used because it is not possible to apply an elongation strain sufficient to estimate the effect on the skin to the test material applied to the film. Furthermore, if the load when the elongation strain reaches 2 is less than 3N, the film will be stretched with a light force, meaning it is too soft, while if the load is more than 12N, a large force will be required to stretch the film, meaning it is too hard, and these properties are not suitable for discovering an agent for improving wrinkles and sagging skin through physical action. That is, even if a test material capable of adjusting the physical properties of a film that is too soft is found, it will not exhibit an effect sufficient to adjust the physical properties of the skin, and screening using a film that is too hard will not change the physical properties of the film unless it imparts a tensile stress greater than that required to improve wrinkles and sagging skin.Furthermore, even a test material that does not increase the maximum load of the present invention may cause physical and mental stress with prolonged and / or repeated use, so that a skin wrinkle and sagging improvement agent suitable for adjusting the physical properties of the skin may be overlooked.In addition, although there are films whose physical properties vary depending on the direction of elongation, any film that can be stretched without breaking in the elongation direction to be tested and has a load of 3 N or more and 12 N or less when the elongation strain reaches 2 can be used.

[0024] The maximum load of the present invention is the maximum load F observed when the film is stretched, the movement of the sample gripper is stopped to maintain the elongation strain, and the load during this process is measured. max This screening method includes a step of selecting a test material that does not substantially increase the maximum load when applied to a film coated with the test material, as an agent for improving skin wrinkles and sagging, when comparing a film coated with nothing to a film coated with nothing. max F of the film coated with the test material max F is the ratio of max It is desirable for the ratio to be 1.1 or less. If it is greater than 1.1, the user will feel a strong sense of tension, which is a factor that will lead to high effectiveness among users, but some people may feel physical and mental stress with prolonged and / or repeated use.

[0025] The relationship between load and elongational strain in the present invention can be measured by any method as long as it can measure the relationship between load and elongational strain during the process of stretching the film. A commercially available device for measuring dynamic viscoelasticity, known as a rheometer, can be used. Furthermore, once the relationship between load and elongational strain is known, the modulus of elasticity can be calculated using Equation 3. This screening method includes a step of selecting a test material that, when comparing a film coated with the test material with a film uncoated, shows no substantial increase in modulus of elasticity upon application as a skin wrinkle and sagging improvement agent. It is desirable for the E ratio, which is the ratio of E of a film coated with the test material to E of a film uncoated, to be 1.1 or less. A ratio greater than 1.1 results in a strong sense of tension, which is a factor in users recognizing high efficacy. However, some people may experience physical and mental stress with prolonged and / or repeated use.

[0026] The rate of load reduction immediately after the movement of the sample gripper of the present invention is v, which is expressed by Equation 5, where F is the load and t is the time, with the point at which the movement of the sample gripper is stopped being time zero. In Equation 5, dF and dt represent the changes in F and t, respectively. There are no particular limitations on the method for calculating v, but it can be determined, for example, by creating a curve representing the relationship between load and time immediately after the movement of the sample gripper is stopped using a fitting method such as that shown in Figure 3, and calculating the value of the first derivative at time t.

[0027]

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[0028] Alternatively, v can be calculated by observing a graph showing the relationship between load and time immediately after the movement of the sample gripper is stopped, as shown in Figure 4, selecting a time t in the range where the relationship can be visually seen as a straight line, and calculating the slope of the line that shows the relationship between the load at time zero and the load at time t (Equation 6), with the point at which the movement of the sample gripper is stopped being time zero. In Equation 6, f(0) is the load at time zero, and f(t) is the load at time t. In this case, f(0) and f(t) do not have to be values ​​obtained experimentally; instead, curves that clearly show the relationship between load and time immediately after the movement of the sample gripper is stopped can be created using a method such as fitting, and the values ​​at time zero and time t of those curves can be used.

[0029]

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[0030] Furthermore, when a film coated with the test material is stretched under uniform speed conditions, i.e., when a film coated with nothing is stretched under the same speed conditions as a film with no coating, the extensional strain includes the concept of time, and t in [Equation 5] and [Equation 6] can be replaced with ε in [Equation 1] to obtain v.

[0031] "Immediately after the movement of the sample gripper is stopped" refers to a time between 0 and 2 seconds, with the time when the movement of the sample gripper is stopped being set as 0, at which a clear difference between the test materials is apparent. For example, this could be 0 to 1 second, or 0 to 0.5 seconds. In the process of selecting a test material that reduces the rate of load decrease immediately after the movement of the sample gripper is stopped when comparing a film coated with the test material to a film without any coating, as a skin wrinkle and sagging improvement agent, it is desirable that the v ratio, which is the ratio of the absolute value of v of the film coated with the test material to the absolute value of v of the film without any coating, be 0.95 or less. If it is greater than 0.95, the effect will not be noticeable.

[0032] When the membrane is subjected to an elongational strain exceeding the yield point, if the absolute value of v decreases when the test material is applied compared to the absolute value of v when nothing is applied, this means that the test material increases the tensile stress of the membrane immediately after the movement of the sample gripper stops. Therefore, if the absolute value of v can be reduced, the test material can be determined to be useful (see Figure 4).

[0033] The membrane of the present invention is not particularly limited in its components, as long as the load at which the elongation strain is 2 is 3N or more and 12N or less, and the yield point is in the range of elongation strain 0.5 or more and 4 or less when a load-elongation strain curve such as that shown in Figure 2 is prepared. If the test material cannot be spread on the membrane due to the water repellency of the membrane, spreading can be achieved by making the membrane surface hydrophilic. The method for achieving hydrophilicity of the membrane surface is not particularly limited, and a membrane produced using a polymer compound with hydrophilic groups can be selected from the beginning. Even if the membrane is produced using a compound that does not have hydrophilicity, hydrophilicity can be imparted by surface treatment such as imparting a microstructure during or after production, introducing hydrophilic groups using plasma, or applying a surfactant. The shape of the membrane is not particularly limited as long as it is suitable for the viscoelasticity measuring device used and the shape of the membrane coated with the test material to be compared matches that of the membrane with nothing coated on it. However, in order to spread the test material evenly and apply an even tensile load to every part of the membrane, the membrane should preferably be 0.5 to 4 cm wide in the direction perpendicular to the extension direction, and more preferably 0.5 to 1.5 cm wide.

[0034] The test material of the present invention is a material to be tested for its potential wrinkle and sagging improvement effect using the screening method of the present invention, and is not particularly limited as long as it can be applied to a membrane. The term "application" as used herein refers to application to a membrane, such as by smearing the material on the membrane, adsorbing it, or attaching it so that changes in the physical properties of the membrane caused by the test material can be reproducibly tested. The test material is not particularly limited as long as it can be applied in this sense. Animal and plant extracts, fungal cultures or their enzyme-treated products, compounds or their derivatives, etc. can also be used, and they can be in liquid, powder, gel, sheet, etc. When testing the effect exhibited by dissolving or dispersing in a solvent, if the material cannot be dissolved or dispersed as is, it can be prepared as a test material by pulverizing or mixing, or by appropriately using a solubilizing agent such as a surfactant. Test materials selected by the screening method of the present invention as being expected to have a wrinkle and sagging improvement effect can be used as wrinkle and sagging improvement agents, and can at least be candidate materials for wrinkle and sagging improvement agents. [Example]

[0035] Examples of the present invention will be specifically described below, but the present invention is not limited to these examples.

[0036] -Membrane selection- This invention was conceived based on the idea that if we could reproduce the response of skin, which has a weakened ability to recover from deformation, to stretching stimuli using a skin substitute and measure the changes in the physical properties of the skin substitute when a test material is applied to the skin substitute, it would be possible to easily screen for agents that improve skin wrinkles and sagging through physical actions, thereby enabling the discovery of a desired agent for improving skin wrinkles and sagging. First, membranes suitable for this purpose were selected. The membranes of Examples 1 and 2 and Comparative Examples 1 to 5 were cut into strips measuring 1 cm wide and 6 cm long, and both ends were held in the sample grip of a rheometer (FUDOH Rheometer RT-2020ND-D, Rheotech) (see Figure 1). The load was applied over a 1 cm length. Next, the membranes were stretched at a rate of 5 mm / s for 4 seconds and then stopped. The changes in load over the course of the stretch, including the next few seconds, were recorded to measure the extensibility, load, and elongation strain at the yield point. "Extensibility" indicates whether the specimen could be stretched up to an elongation strain of 2 without breaking (◯ if yes, × if no), and "load" indicates the load at an elongation strain of 2. The results are shown in Table 1.

[0037] [Table 1]

[0038] As can be seen from Table 1, when Example 4, which has been confirmed to have a wrinkle-improving effect in the human use test described below, was applied to the films of Examples 1 and 2, which had a load of 12 N and a yield point strain of less than 4, a decrease in the v ratio was observed, whereas in Comparative Examples 1 and 2, which had a load of 12 N and / or a yield point strain of more than 4, there was almost no change in the v ratio due to the application of Example 3. Furthermore, when Comparative Example 9, which did not show any wrinkle-improving effect in the human use test, was applied, the v ratio of Example 1 only decreased slightly, whereas that of Comparative Example 3 decreased significantly. In other words, in Comparative Example 1, where the load exceeded 12N and the yield strain exceeded 4, and in Comparative Example 2, where the load was less than 12N but the yield strain exceeded 4, test materials capable of adjusting the physical properties of the skin were overlooked.Furthermore, in Comparative Example 3, where the load was less than 3N, the test material was too soft, causing inconvenience in experimental operation, and even when applied, it had a significant effect on v, making it insufficient to adjust the physical properties of the skin, and was selected as a skin wrinkle and sagging improvement agent.In Comparative Examples 4 and 5, breakage occurred during the application of elongation strain, making them unsuitable for use in testing.

[0039] -Screening of agents for improving wrinkles and sagging skin 1- The membrane of Example 1 (soft polyethylene, approximately 110 μm thick, density 0.91–0.92) was cut into strips 1 cm wide and 6 cm long and hydrophilized using a plasma treatment device (PC-06D, Strex) with silent discharge under reduced pressure (approximately 9 kV, 11–14 kHz, effective current 20 mA). After this treatment, the contact angle of purified water dropped onto the membrane was approximately 63°. Both membranes were prepared with and without the test material. The membrane to be coated with the test material was prepared by spreading approximately 0.01 g of the test material evenly over a 1 cm square area in the center of the membrane with a spatula and allowing it to air-dry overnight. After confirming that the test material had adhered to the membrane, both ends of the membrane were held in the sample holder of a rheometer (FUDOH Rheometer RT-2020ND·D, Rheotech) so that the membrane was stretched in the same direction as when the membrane was selected (see Figure 1). The length of the load applied was 1 cm. Next, the membrane was stretched at a rate of 5 mm / s for 4 seconds, then stopped. The load change was recorded over the next few seconds. No membrane fracture occurred during this process. The maximum load was determined from the relationship between load and extensional strain shown in Figure 2. In this example, the maximum load was observed when the membrane was stretched at a rate of 5 mm / s for 4 seconds, i.e., when the extensional strain was 2. Next, from the load-time relationship shown in Figure 3, the load drop rate was calculated by setting the time when the sample gripper movement was stopped as 0 to 0.5 seconds, which corresponds to the time immediately after the sample gripper movement was stopped. More specifically, a fitting curve was created that closely reproduced the relationship between time and load, with 0 being the time when the sample gripper movement was stopped, and the load drop rate immediately after the sample gripper movement was calculated using the following equation (7).

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[0040] The measurement results for Examples 3 to 5 and Comparative Examples 8 and 9 listed in Table 5 are shown in Figure 5. The vertical axis of Figure 5 plots the F of the film without any coating (Comparative Example 7). max F of the film coated with the test material max F is the ratio of maxThe horizontal axis is the v ratio, which is the ratio of the absolute value of v of the film to which the test material was applied to the absolute value of v of the film to which nothing was applied. max The range of the ratio below 1.1 and the range of the v ratio below 0.95 are shown in gray. max The first quadrant is where the ratio and v ratio are both 1 or more. max The part where the ratio is 1 or more and the v ratio is less than 1 is the second quadrant, F max The part where the ratio and v ratio are both less than 1 is the third quadrant, F max The portion where the v ratio is less than 1 and greater than 1 is referred to as the fourth quadrant and is entered in the corresponding quadrant. In the first aspect of the present invention, a tensile load is applied to a film coated with a test material such that the elongation strain exceeds the yield point, and then the movement of the sample gripper is stopped to maintain the elongation strain. The test material for which the rate of load decrease immediately after the sample gripper is stopped is selected as the desired skin wrinkle and sagging improvement agent. That is, test materials plotted in the second and third quadrants of Figure 5, such as Examples 3 and 4, are selected as the desired skin wrinkle and sagging improvement agent. In the second aspect of the present invention, a test material for which the maximum observed load does not increase upon application and the rate of load decrease immediately after the sample gripper is stopped is smaller than that of a film without any application is selected. Therefore, test materials plotted in the third quadrant of Figure 5, such as Examples 4 and 5, are primarily selected as the desired skin wrinkle and sagging improvement agent. The selection criteria are described in paragraph 0055, taking into account the results that follow.

[0041] -Human Use Test: Evaluation of Immediate Anti-Wrinkle Effects 1- A practical use test was conducted to determine the relationship between screening results for skin wrinkle and sagging improvement agents and their immediate anti-wrinkle effects. Two men in their 40s (two subjects each) were asked to wash their faces and then rest for 20 minutes at 22°C and 50% humidity. The formulations of each lotion sample are shown in Table 2. Approximately 300 μL of each sample was then dropped onto a cotton pad, and the tester applied the sample to the entire outer corner of the test subject's eye. The subject was then allowed to rest for 15 minutes. The three-dimensional shape of the outer corner of the eye was then measured using a three-dimensional image analysis system (PRIMOS-CR, Canfield Scientific). Next, the subject blinked strongly five times, and after three minutes (referred to as "after blinking"), the three-dimensional shape was measured. The wrinkle area ratio before blinking and the reduction rate of each measurement value after blinking from the total wrinkle volume were calculated using [Equation 8] and [Equation 9]. The wrinkle area ratio was calculated as the ratio of the wrinkled area (having a depth of 40 μm or more and a projected area on the above plane of 0.1 mm) to the area of ​​the analysis target area (a 10 mm x 10 mm range with the perpendicular bisector of one side of a square on an approximately straight line connecting the inner and outer canthus of the eye, and the center located approximately 10 mm from the outer canthus of the eye) in the planar image capturing the wrinkles. 2 The ratio of the projected area of ​​the dents (those with an area of ​​100 or more) to the above plane was taken as the wrinkle area ratio, and the sum of the detected dent volumes was taken as the total wrinkle volume. [Table 2]

[0042]

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[0043]

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[0044] The measurement results are shown in Figure 6. A high reduction rate was observed in both the wrinkle area ratio (Figure 6(a)) and total wrinkle volume (Figure 6(b)) in the treatment group. Therefore, it was confirmed that the polyvinyl alcohol of Example 4 not only prevents the increase in wrinkle area ratio and total wrinkle volume caused by blinking, but also has a high wrinkle-improving effect by immediately reducing wrinkles that were present in the steady state before blinking.

[0045] -Human Use Test: Evaluation of Immediate Anti-Wrinkle Effects 2- A practical use test was conducted to determine the relationship between screening 1 and immediate anti-wrinkle effects for skin wrinkle and sagging improvement agents. Two men in their 40s (two subjects each) were asked to wash their faces and then rest for 20 minutes at 22°C and 50% humidity. The formulations of each lotion sample are shown in Table 3. Approximately 1 mL of each sample was then dispensed onto a cotton pad, which the tester then applied to the entire outer corner of the test subject's eye, allowing the subject to rest for 15 minutes. Then, as in "Human Actual Use Test: Evaluation of Immediate Anti-Wrinkle Effect 1," the reduction rate of each measurement value after blinking from the wrinkle area ratio before blinking and the total wrinkle volume was calculated.

[0046] [Table 3]

[0047] As a result of the measurements, no difference was observed between the treatment group and the comparison group in either the reduction rate of wrinkle area ratio or the reduction rate of total wrinkle volume. Therefore, it was confirmed that O-[2-hydroxy-3-(trimethylammonio)propyl]hydroxyethylcellulose chloride of Comparative Example 9 has no effect of preventing the increase in wrinkle area ratio and total wrinkle volume caused by blinking.

[0048] -Human use test: Evaluation of anti-wrinkle effects over time- To determine the relationship between Screening 1 of the skin wrinkle and sagging improvement agent and its anti-wrinkle effect over time, a practical use test was conducted, and the three-dimensional shape of the area around the eyes was measured before and after the test. Test participants (two men in their 50s) applied approximately 0.2 g of Emulsion Example 1 (the emulsion sample containing 6% polyvinyl alcohol in Example 4) and Emulsion Example 2 (the emulsion sample without polyvinyl alcohol) to the corners of each eye once every morning for two weeks. The side to which Emulsion Example 1 was applied is referred to as the test side, and the side to which Emulsion Example 2 was applied is referred to as the comparison side. The formulations of each emulsion example are shown in Table 4. To determine the three-dimensional shape of the area around the eyes, subjects were asked to wash their faces and rest for 15 minutes at 22°C and 50% humidity. Images of the area around the eyes were then taken using a three-dimensional image analysis system (PRIMOS-CR). The lengths of any wrinkles visually observed around the eyes before and after the test were measured on the images, and the average wrinkle length was calculated. The wrinkle length change rate was calculated using the following equation (10). [Table 4]

[0049]

number

[0050] The average change in wrinkle length for the test participants was 0.54 for the treatment group and 1.31 for the comparison group. An example of the changes observed in the test participants is shown in Figure 7. Focusing on the area around the white triangle, comparing the area before and after two weeks of use, it is clear that wrinkles are less visible on the treatment group. On the other hand, no clear change in wrinkles was observed on the comparison group. From the above, it was confirmed that the polyvinyl alcohol of Example 4 has a significant effect on improving wrinkles over time.

[0051] -Screening of agents for improving wrinkles and sagging skin 2- The membrane from Example 1 (approximately 100 μm thick) was cut into strips 1 cm wide and 6 cm long. The membrane was hydrophilized using a plasma treatment device (PC-06D, Strex) under reduced pressure and silent discharge (approximately 9 kV, 11–14 kHz, 20 mA RMS current). Two membranes were prepared: one coated with the test material and the other uncoated. The membrane to be coated with the test material was prepared by spreading approximately 0.01 g of the test material evenly over a 1 cm square area in the center of the membrane using a spatula and air-drying overnight. After confirming that the test material had adhered to the membrane, both ends were held in the sample grip of a rheometer (FUDOH Rheometer RT-2020ND·D, Rheotech). The load was applied over a 1 cm length. The membrane was then stretched at a rate of 5 mm / s for 4 seconds and then stopped. No membrane rupture occurred during this process. From the observation of the relationship between load and elongation strain as shown in Figure 2, a fitting line that closely reproduces the relationship between load and elongation strain before the yield point was determined, and the slope of the fitting line was calculated as the elastic modulus from the relationship in Equation 3.

[0052] The measurement results for Examples 3 to 5 and Comparative Examples 8 and 9 listed in Table 5 are shown in Figure 8. The vertical axis of Figure 8 represents the E ratio, which is the ratio of E for the film coated with the test material to E for the film without any coating (Comparative Example 7), and the horizontal axis represents the v ratio, which is the ratio of the absolute value of v for the film without any coating. In Figure 8, the range of E ratios of 1.1 or less and v ratios of 0.95 or less, which are expected to be effective in improving skin wrinkles and sagging, are indicated by gray shading. Furthermore, in Figure 8, areas where the E ratio and v ratio are both 1 or greater are designated as the first quadrant, areas where the E ratio is 1 or greater and the v ratio is less than 1 are designated as the second quadrant, areas where the E ratio and v ratio are both less than 1 are designated as the third quadrant, and areas where the E ratio is less than 1 and the v ratio is 1 or greater are designated as the fourth quadrant. The corresponding quadrants are shown. In the third aspect of the present invention, when a film coated with a test material is compared with a film not coated with anything, a test material that does not increase the modulus of elasticity due to the application and that reduces the rate of load decrease under a constant elongation strain immediately after the movement of the sample gripper is stopped can be selected as a skin wrinkle and sagging improvement agent. In general, test materials plotted in the third quadrant in Figure 8, such as Examples 4 and 5, are selected as the desired skin wrinkle and sagging improvement agent.

[0053] - Evaluation of usability - Two men in their 40s and two men in their 50s were asked to apply Examples 3 to 5 and Comparative Examples 7 to 10 to their faces, and to evaluate the "resistance felt when facial expressions changed" during application. The evaluation criteria were as follows:

[0054] [Usability evaluation criteria] "Resistance when changing facial expressions" Very: 3 Somewhat: 2 No:1

[0055] The evaluation results of the feeling of use are shown in Table 5 together with the results of paragraphs 0039 to 0054. The "resistance when facial expression changes" in Table 5 is the average value of the evaluations by the test participants. As shown in Table 5, Examples 3 and 4 selected by the method of the first invention of the present invention, and Examples 4 and 5 selected by the methods of the second and third inventions of the present invention all showed little resistance when facial expression changed, and Example 4 showed an immediate wrinkle improvement effect due to the improvement of the skin's recovery function from deformation, as well as an effect of wrinkle improvement over time. On the other hand, the E ratio and F ratio, respectively, max In Comparative Examples 8 and 9, which had a large ratio, there was a strong sense of resistance when facial expressions changed, and in Comparative Example 9, which had a small v ratio, no immediate effect was observed, and therefore no effect over time could be expected. From these results, it is possible to select the test materials plotted in the quadrant that corresponds to each invention as the desired skin wrinkle and sagging improvement agent, but more detailed criteria for selecting a skin wrinkle and sagging improvement agent that does not cause stress to the mind and body even with prolonged and / or repeated use and can adjust the physical properties of the skin through physical action are a v ratio of 0.95 or less in terms of effect on the skin, and F in terms of usability. max A ratio of 1.1 or less and an E ratio of 1.1 or less are suitable.

[0056] [Table 5] [Industrial Applicability]

[0057] The present invention provides a skin wrinkle and sagging improvement agent that uses a physical action to improve wrinkles and sagging skin, which can be expected to improve wrinkles and sagging skin to a level and for a period of time that satisfies the user, and which does not cause physical or mental stress even with long-term and / or repeated use, and a simple screening method for the agent.The present invention also provides a membrane for simple screening of skin wrinkle and sagging improvement agents that can adjust the physical properties of the skin.

Claims

1. A method for screening an agent for improving wrinkles and sagging skin, comprising the following steps: (1) A step of holding both ends of a film in the sample gripping portion of a viscoelasticity measuring device and stretching it, and applying a test material to a film whose load when the elongation strain indicates 2 is 3 N or more and 12 N or less, and whose yield point is in the range of elongation strain 0.5 or more and 4 or less. (2) A step of holding both ends of the film in the sample holder of the viscoelasticity measuring device and stretching it to an extent that an elongation strain exceeding the yield point occurs, and then stopping the movement of the sample holder to maintain the elongation strain. (3) A step of measuring the load change in the step (2). (4) A step of selecting a test material that reduces the rate of decrease in load immediately after the movement of the sample gripper is stopped when comparing a film coated with the test material to a film without any coating, as an agent for improving skin wrinkles and sagging.

2. A method for screening an agent for improving wrinkles and sagging skin, comprising the following steps: (1) A step of holding both ends of a film in the sample gripping portion of a viscoelasticity measuring device and stretching it, and applying a test material to a film whose load when the elongation strain indicates 2 is 3 N or more and 12 N or less, and whose yield point is in the range of elongation strain 0.5 or more and 4 or less. (2) A step of holding both ends of the film in the sample holder of the viscoelasticity measuring device and stretching it to an extent that an elongation strain exceeding the yield point occurs, and then stopping the movement of the sample holder to maintain the elongation strain. (3) A step of measuring the load change in the step (2). (4) A step of selecting a test material as an agent for improving skin wrinkles and sagging, in which the maximum load observed in (3) does not increase when the test material is applied to a film that has not been applied, and the rate at which the load decreases immediately after the movement of the sample gripper is stopped, when compared with a film to which nothing is applied.

3. The method for screening an agent for improving wrinkles and sagging skin includes the following steps: (1) A step of holding both ends of a film in the sample gripping portion of a viscoelasticity measuring device and stretching it, and applying a test material to a film whose load when the elongation strain indicates 2 is 3 N or more and 12 N or less, and whose yield point is in the range of elongation strain 0.5 or more and 4 or less. (2) A step of holding both ends of the film in the sample holder of the viscoelasticity measuring device and stretching it to an extent that an elongation strain exceeding the yield point occurs, and then stopping the movement of the sample holder to maintain the elongation strain. (3) A step of measuring the load change in the step (2). (4) A step of selecting a test material as an agent for improving skin wrinkles and sagging, in which the elastic modulus calculated from the measurement in (3) does not increase when the test material is applied to a film compared with a film to which nothing is applied, and the rate of decrease in the load immediately after the movement of the sample gripper is stopped decreases when the test material is applied to a film to which nothing is applied.

4. The method for screening an agent for improving wrinkles and sagging skin according to any one of claims 1 to 3, wherein the surface of the film is hydrophilic.

5. A membrane used in the method for screening an agent for improving skin wrinkles and sagging according to any one of claims 1 to 4.

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