JPH10281965A - Estimation of antifouling activity of chemical substance and screening of compound involving antifouling activity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To evaluate antifouling activity easily in a short time and screen compound by making an estimation from the relation between the oscillation frequency change of a crystal oscillator coated with lipid membrane in adding chemical substance, and antifouling activity. SOLUTION: Chemical substance whose antifouling activity is to be discriminated is added in water in which a crystal oscillator coated with lipid membrane is immersed, and the water surrounding the crystal oscillator is then replaced with water including no chemical substance. A change in the oscillation frequency is observed until the oscillation frequency of the crystal oscillator is stabilized. The characteristics which meet the change in the oscillation frequency, that is, the sorption speed and desorption speed of the chemical substance to/from the lipid membrane, the ratio of the partition coefficient of the chemical substance against the lipid membrane in a lipid membrane aqueous system, to the sorption speed, and the ratio of the partition coefficient to the desorption speed, are obtained. It is possible to estimate the antifouling activity of the chemical substance based on the relation between the antifouling activity which is obtained previously and the above characteristics, and screen a compound having the antifouling activity.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for estimating the antifouling activity of a chemical substance and a method for screening a compound having an antifouling activity.

[0002]

2. Description of the Related Art Conventionally, activity evaluation and screening of an antifouling agent are carried out by actually immersing a test plate coated with a sample in seawater and examining the presence or absence of marine organisms for three months to several years. It is done by that.

[0003] Contamination of marine structures and the like due to the attachment of marine organisms first occurs when bacteria grow near the surface to form a bacterial coating, and then the attached algae and microalgae grow to form a slime layer. This slime layer progresses by inducing larval settlement and metamorphosis of various large marine organisms, and finally undergoes a process in which large organisms such as barnacles, mussels, and blue seaweed adhere.

In view of this contamination process, in order to prevent the adhesion of marine organisms, it is necessary to prevent the growth of bacteria in the vicinity of marine structures that serve as substrates for the adhesion, and to prevent algae, large marine organisms and the like from adhering. It is very effective to kill or paralyze epiphytic larvae of higher organisms. Therefore, the antifouling object can be effectively achieved by adding a substance having an activity of controlling these organisms to the coating film.

As a substance having such an activity, an inorganic heavy metal compound or the like has hitherto been used. However, in recent years, importance has been placed on environmental safety, and therefore, a material having a small environmental load and a high antifouling activity has been demanded. In order to select such substances, it is necessary to confirm the activity of various substances against the above-mentioned bacteria and higher organisms, but there are a very large number of target substances. However, in the conventional antifouling activity evaluation method and screening method, each of the samples must be applied to a test plate, and it is difficult to process a large number of samples at a time, and a single test period is very long. Therefore, it is extremely difficult to confirm the antifouling activity of all of them. Therefore,
It is necessary to preliminarily narrow down compounds having a high antifouling activity from among a large number of substances and conduct a truly effective actual exposure test.

[0006] By the way, since the activity evaluation of a physiologically active substance using a lipid membrane can be detected without using a living body and even a trace amount of a physiologically active substance, it can be used in various fields. Expected. Many of the physiologically active substances directly act on the lipid portion of the cell membrane, and it is thought that the process of adsorption to the cell membrane proceeds as the first step in the mechanism of action. It is thought that the adsorption of the physiologically active substance to the cell membrane is not caused by a chemical reaction between the physiologically active substance and the cell membrane, but by a physical process. The same is true for the synthetic bilayer membrane which is an artificial lipid membrane. Has been confirmed to occur. Therefore, if a synthetic bilayer film is used instead of a cell membrane as an experimental system, it is possible to efficiently evaluate the activity of a physiologically active substance.

In a method for evaluating activity using a synthetic bilayer film, a quartz oscillator can be used as a device for measuring the adsorption behavior of a physiologically active substance on a lipid membrane. Since the frequency of the crystal oscillator fluctuates due to the change in the weight of the electrodes of the crystal oscillator, a crystal oscillator whose surface is covered with a lipid film is used to contact the sample, and then the crystal oscillator By measuring the oscillation frequency of
It is possible to confirm whether or not the substance is adsorbed on the lipid membrane, and when the substance is adsorbed on the lipid membrane, it is also possible to confirm the amount of adsorption.

As an alternative to animal experiments, such an activity evaluation method is currently used to evaluate the effects of odorants on olfactory cells, bitter substances on taste cells, anesthetics on nerve cells, etc. It is used for evaluation of activity on sensory organs of a living body. These activities are assessed by the partition coefficient of the substance on the lipid membrane. This partition coefficient is calculated from the change of the oscillation frequency of the crystal oscillator covered with the lipid membrane.
It can be derived by measuring the amount of absorption of a substance.

Japanese Patent Application Laid-Open No. 3-115858 discloses a method in which a crystal oscillator coated with a lipid membrane is used to contact a drug with the crystal oscillator in distilled water or deionized water, and if necessary, in low ionic strength water. A method for evaluating the physiological activity of a drug by measuring the oscillation frequency that changes when the drug is released has been disclosed. This technique states that the activity of a drug can be accurately reflected only by the lipid membrane-water partition coefficient.

[0010] However, when such an evaluation method is applied to the evaluation and screening of the activity of an antifouling agent, the antifouling activity is insufficient even if the antifouling activity is determined by the lipid membrane-water partition coefficient. There is something. This is because the action of the physiologically active substance on the living body does not depend only on the amount of the substance adsorbed on the lipid membrane, but depends on the concentration of the substance to be administered, other physical conditions, environmental conditions, and the like. is there. In particular, in a single-celled organism such as bacteria,
Since the cell membrane itself is the boundary with the outside world, the functional characteristics of the cell are regulated by environmental conditions, and as a result, the sensitivity to the substance may change, so lipids measured in fresh water or low ionic strength water The membrane-water partition coefficient cannot be used as an indicator of the antifouling activity of a substance. Therefore, when the activity evaluation method using a quartz oscillator covered with a lipid membrane is used for the evaluation and screening of the antifouling agent, the measurement conditions are approximated to the environment where the attached marine organisms and bacteria live. Need to be done.

It is difficult to simply derive a correlation between the antifouling activity and the lipid membrane-water partition coefficient.
The present inventors have confirmed that no correlation can be found between such a distribution coefficient and antifouling activity as shown in FIG.

[0012]

SUMMARY OF THE INVENTION In view of the above situation, the present invention provides a method for estimating the antifouling activity of a chemical substance, which can evaluate the antifouling activity simply and in a short time. Among them, an object of the present invention is to provide a screening method capable of efficiently selecting a compound having an antifouling activity.

[0013]

Means for Solving the Problems The present inventors paid attention to the change in the oscillation frequency of the crystal oscillation coated with the lipid membrane when a chemical substance was added, and obtained various characteristics corresponding to this change. As a result of repeated studies, they have found that the antifouling activity of the chemical substance can be estimated from the relationship between the antifouling activity and the above properties, and have completed the present invention. Among them, the antifouling activity of the chemical substance and the sorption rate and desorption rate to the lipid membrane, the ratio between the partition coefficient and the sorption rate of the chemical substance to the lipid membrane in the lipid membrane-water system, and the partition coefficient and the desorption rate It has been found that the ratio of speed has a close relationship with the antifouling activity of the chemical. In this specification, "antifouling activity"
The term "pharmacological activity" has some effect on the growth and life support of living organisms such as fungicidal activity, bactericidal activity, insecticidal activity, etc., in addition to the property of preventing the attachment of marine organisms.

That is, according to the present invention, a chemical substance whose antifouling activity is to be determined is added to water immersed in a quartz oscillator coated with a lipid membrane, and then water around the quartz oscillator is washed with the chemical substance. Is replaced with water that does not contain, the oscillation frequency of the crystal oscillator until the oscillation frequency of the crystal oscillator becomes stable after replacement with water that does not contain the chemical substance after the addition of the chemical substance A method of observing the change by an oscillation frequency measuring device to obtain a characteristic corresponding to the change in the oscillation frequency, and estimating the antifouling activity of the chemical substance from the relationship between the antifouling activity and the characteristic obtained in advance. It is.

The present invention also provides a method for preparing a lipid membrane having an ion complex type bilayer membrane of dioctadecyldimethylammonium salt and polystyrene sulfonic acid as described above, wherein the yield is within the range of 100 to 2000 mg / min. Desorption rate, desorption rate in the range of 10-1500 mg / min, 0.
The ratio of the sorption rate to the partition coefficient of the chemical to the lipid membrane in the lipid membrane-water system in the range of 3-80, 0.3-80;
The present invention is also a method for screening a compound having an antifouling activity for selecting a chemical substance having a ratio between the partition coefficient and the desorption rate in the range of 200. Hereinafter, the present invention will be described in detail.

A chemical substance whose antifouling activity is to be determined is added to water immersed in a crystal oscillator coated with a lipid membrane, and then water around the crystal oscillator is replaced with water not containing the chemical substance. The change in the oscillation frequency of the crystal oscillator when the oscillation frequency is changed typically includes a process in which the oscillation frequency decreases, a process in which the oscillation frequency reaches a constant oscillation frequency as shown in FIG. It is known that the process of increasing the frequency consists of three phases. The present invention analyzes in detail the relationship between the change in the oscillation frequency indicated by these processes and the antifouling activity of the chemical substance.

The crystal oscillator used in the present invention is a device in which electrodes of a metal such as gold, silver, or aluminum are deposited on both surfaces of a thin quartz plate, and the surface is covered with a lipid film. The quartz oscillator is not particularly limited, and may be, for example, a known quartz oscillator such as a 9 MHz or 27 MHz AT-cut gold electrode quartz oscillator. In the present invention, since the crystal oscillator is used in seawater, it is preferable to use a single-sided barrier-coated crystal oscillator in which one surface of both electrodes of the crystal oscillator is covered with a barrier via a certain space. .

The above lipid membrane is composed of a unit membrane (U
Preferably, it is a single-layer bilayer or cumulative film based on M). The UM is not particularly limited, and may be, for example, a synthetic lipid membrane such as an ion complex type synthetic bilayer membrane of dioctadecyldimethylammonium salt and polystyrene sulfonic acid; Examples include lipid membranes. Among them, an ion complex type synthetic bilayer membrane of a dioctadecyldimethylammonium salt and polystyrenesulfonic acid is preferable because a bilayer membrane can be easily formed.

The UM is coated on the surface of the quartz oscillator to form a lipid film. The coating method is not particularly limited, and may be formed into a film on the surface of the quartz oscillator, incubated at a phase transition temperature or higher and oriented to form a monolayer or multilayer bilayer, or a Langmuir-Blodgett method. For example, a cumulative film may be formed. The amount of the lipid film coated on the surface of the crystal oscillator is not particularly limited, but is preferably 2 to 50 μg in the present invention.

The chemical substance added to the water is not particularly limited as long as it is a compound whose antifouling activity is to be determined.
The chemical substance is preferably added so that the concentration in water is 0.1 to 100 μM. When the concentration is less than 0.1 μM, the concentration of the chemical substance adsorbed on the lipid membrane is too small, so that an error easily occurs. When the concentration exceeds 100 μM, the amount absorbed on the lipid membrane becomes saturated, and the distribution coefficient is measured. Can not do it.

The change in the oscillation frequency of the crystal oscillator caused by the addition of the chemical substance is observed by an oscillation frequency measurement device such as a frequency counter connected to the crystal oscillator. When the chemical substance is adsorbed on the lipid film covering the surface of the crystal oscillator, the oscillation frequency of the crystal oscillator decreases. When the sorption reaches an equilibrium state, the oscillation frequency does not decrease and stabilizes at a constant value. Since the amount of change in the oscillation frequency is proportional to the amount of the substance attached to the electrode, the amount of sorption of the sample to the lipid membrane can be easily calculated from the amount of change in the oscillation frequency.

The above 9 MHz crystal oscillator is usually 1n
Since a change in the oscillation frequency of about 1 Hz occurs with respect to a change in the weight of g, a very small change in the mass can be measured with high sensitivity and high accuracy.

In the present invention, after the chemical substance is added to stabilize the oscillation frequency of the crystal oscillator, water around the crystal oscillator is replaced with water not containing the chemical substance. At this time, the oscillation frequency of the crystal oscillator is
It increases as the lipid membrane desorbs the chemical. The change in the oscillation frequency in this case can also be observed by an oscillation frequency measurement device such as the above-described frequency counter.

In the present invention, the characteristic of the chemical substance corresponding to the change of the oscillation frequency when the chemical substance whose antifouling activity is to be determined is added or removed is determined, and the previously determined characteristic and antifouling activity are compared. The antifouling activity of the chemical substance to be determined is estimated in light of the relationship The above characteristics include
For example, the sorption rate of the chemical substance to the lipid membrane, the desorption rate of the chemical substance from the lipid membrane, the ratio of the sorption rate of the chemical substance to the lipid membrane in the lipid membrane-water system and the sorption rate, and the partition coefficient The ratio with the above-mentioned desorption speed can be mentioned.

The sorption rate can be derived from the rate of decrease of the oscillation frequency observed after the addition of the chemical substance (indicated by ↓ in FIG. 1), as shown in FIG. this is,
This corresponds to a phenomenon in which the chemical substance is added to the lipid membrane in some process such as adsorption and dissolution, and as a result, the amount of the substance on the electrode of the crystal oscillator increases.

The present inventors have developed various chemical substances,
It has been found that the sorption rate has a close relationship with the antifouling activity of the chemical. The sorption rate and the antifouling activity typically show a negative correlation as shown in FIG. Such a relationship between the sorption rate and the antifouling activity of the chemical substance is first reported by the present inventors. In addition, FRAGANCE JOURNAL 19
90-8, pp. 92-96, describe an alternative method of biotoxicity testing using artificial lipid membranes and quartz oscillators, which disclose the partition coefficient of irritants and the toxicity to animals. Are excellent correlations, and fall short of the existence of a correlation between biotoxicity and sorption rate.

As shown in FIG. 1, the desorption rate was determined by replacing the water around the crystal oscillator with water not containing the chemical substance whose antifouling activity is to be estimated (indicated by ↑ in FIG. 1). It can be derived from the rate of increase of the oscillation frequency that occurs later.
This corresponds to a phenomenon in which the chemical substance is desorbed from the lipid membrane into water, and as a result, the amount of the substance on the electrode of the crystal oscillator is reduced. The inventors have also found that for various chemicals, this desorption rate is closely related to the antifouling activity of the chemical. The desorption rate and the antifouling activity typically show a negative correlation as shown in FIG.

Furthermore, surprisingly, the sorption rate and lipid membrane-
It has been found that the ratio of the chemical substance to the lipid membrane in the aqueous system and the ratio between the desorption rate and the partition coefficient each show a very close correlation with the antifouling activity of the chemical substance. That is, for the various chemical substances, the ratio between the sorption rate and the distribution coefficient and the antifouling activity typically show a positive correlation as shown in FIG. In addition, the ratio between the desorption rate and the distribution rate and the antifouling activity typically show a positive correlation as shown in FIG.

Here, the partition coefficient of the chemical substance to the lipid membrane can be obtained by the following equation (1). (Partition coefficient) = {(Amount of sorbed chemical substance on lipid membrane) / (Amount of lipid membrane)} / (Concentration of chemical substance in water) (1)

The method for estimating the antifouling activity of a chemical substance according to the present invention typically employs the method described in the above 4 corresponding to the change in oscillation frequency.
It exploits the correlation between species properties and antifouling activity. For this reason, the antifouling activity can be estimated in a short time using a crystal oscillator, which is simpler than the conventional antifouling activity evaluation method, and it is necessary to know the antifouling activity of a large number of chemical substances. It is suitable when there is.

The method for screening a compound having an antifouling activity of the present invention is carried out by using the above method for estimating the antifouling activity of the chemical substance of the present invention. In the method for screening a compound having an antifouling activity of the present invention, an ion complex type synthetic bilayer membrane of dioctadecyldimethylammonium salt and polystyrenesulfonic acid is used as the lipid membrane.

As described above, the characteristics corresponding to the change in the oscillation frequency, namely, the sorption speed, the desorption speed, the ratio between the distribution coefficient and the sorption speed, the distribution coefficient and the desorption speed, And the antifouling activity of the chemical substance show a correlation. Therefore, for each of the characteristics corresponding to the change in the oscillation frequency, it is possible to determine a range of values at which excellent antifouling activity is exhibited.

When the sorption rate is selected as an index of the antifouling activity, in the screening method of the present invention, a chemical substance having a sorption rate of 100 to 2000 mg / min is selected. Preferably, it is 150 to 1200 mg / min.

When the desorption rate is selected as an indicator of the antifouling activity, in the screening method of the present invention, chemical substances having a desorption rate of 10 to 1500 mg / min are selected. Preferably, it is 20 to 1200 mg / min.

When the ratio between the distribution coefficient and the sorption speed is selected as an index of the antifouling activity, in the screening method of the present invention, the ratio between the distribution coefficient and the sorption speed is 0.3 to 8
The chemicals that are 0 are sorted out. Preferably, 0.4 to 4
0.

When the ratio between the partition coefficient and the desorption rate is selected as an index of the antifouling activity, in the screening method of the present invention, the ratio between the partition coefficient and the desorption rate is 0.3 to 2
Sort out chemicals that are 00. Preferably, 0.8-
120.

In the present invention, screening can be carried out based on any one of the above-mentioned characteristics, but it is also possible to carry out screening by appropriately combining these characteristics.

Since the method for screening a compound having an antifouling activity of the present invention is carried out using the above-described method for estimating the antifouling activity of the chemical substance of the present invention, it is possible to reduce the time spent for screening. This is suitable for efficiently selecting a compound having an antifouling activity from a large number of chemical substances.

[0039]

BEST MODE FOR CARRYING OUT THE INVENTION Relationship between antifouling activity and sorption speed Using an oscillation frequency measuring device, a quartz oscillator having the following antifouling agents (I) to (VII) was added. A change in the oscillation frequency was observed. The crystal oscillator used is 9M
Hz, AT-cut gold electrode crystal oscillator, and the lipid membrane was an ion complex type synthetic bilayer membrane of dioctadecyldimethylammonium salt and polystyrenesulfonic acid. This crystal oscillator has 1.05 Hz with an adsorption amount of 1 ng.
Was a change in From the obtained change in the oscillation frequency, the sorption speed of each antifouling agent was determined and is shown in Table 1. Table 1 also shows the antifouling activity of these antifouling agents. The antifouling activity was evaluated by the method described below.

Evaluation of antifouling activity Butyral resin containing 20% by weight of each test compound was
A dry film thickness of 80-100
μm, dried and then immersed in a depth of 1 m in the sea to check the degree of contamination by attached organisms over time. ) Was measured.

The relationship between the determined sorption speed and the antifouling activity was examined. The results are shown in FIG. Table 1 shows the correlation coefficient in this case.

Compound (I): 2-methylthio-4-t-
Butylamino-6-cyclopropylamino-S-triazine Compound (II): N, N-dimethyldichlorophenylurea Compound (III): 4,5-dichloro-2-n-octyl-3 (2H) isothiazolone Compound (IV) : N-fluorodichloromethylthio) phthalimide Compound (V): 2,3,5,6-tetrachloro-4-
(Methylsulfonyl) pyridine Compound (VI): 3-Iodo-2-propenylbutylcarbamate Compound (VII): Tributyltin oxide

Relationship between Antifouling Activity and Desorption Rate As in the case of the relationship between the antifouling activity and the sorption rate, the desorption rate of each antifouling agent was determined. This is shown in Table 1. Further, the relationship between the determined desorption rate and the antifouling activity was examined. The results are shown in FIG.

Relationship between antifouling activity and distribution coefficient / sorption speed As in the case of the above-described relationship between antifouling activity and sorption speed, a change in oscillation frequency was observed using a quartz oscillator, and the above equation was used. The distribution coefficient was determined using (1), and is shown in Table 1. The sorption speed determined in relation to the sorption speed,
From the above distribution coefficient, a value of distribution coefficient / sorption speed is obtained,
This is shown in Table 1. Further, the relationship between the obtained distribution coefficient / sorption rate and the antifouling activity was examined. The results are shown in FIG.

Relationship between antifouling activity and distribution coefficient / desorption speed The distribution coefficient obtained in the relationship between the antifouling activity and the distribution coefficient / sorption speed, and the desorption obtained in the relationship between the antifouling activity and the desorption speed. The value of the distribution coefficient / desorption rate was determined from the rate, and is shown in Table 1. Further, the relationship between the obtained distribution coefficient / desorption rate and the antifouling activity was examined. The results are shown in FIG.

Relationship between antifouling activity and partition coefficient As a comparison , the relationship between the antifouling activity and the partition coefficient was examined. The values shown in Table 1 were used as the antifouling activity and the distribution coefficient. The results are shown in FIG.

[0047]

[Table 1]

FIG. 2 shows that the sorption rate and the antifouling activity show a good negative correlation with a correlation coefficient of -0.81. From FIG. 3, the desorption rate and the antifouling activity show a correlation coefficient −
It was found to show a good negative correlation of 0.71. From FIG. 4, it was found that the distribution coefficient / sorption rate and the antifouling activity show a good positive correlation with a correlation coefficient of 0.76. From FIG. 5, it was found that the distribution coefficient / desorption rate and the antifouling activity exhibited a good positive correlation with a correlation coefficient of 0.93.

Therefore, by utilizing these relationships, at least one of the sorption rate, desorption rate, distribution coefficient / sorption rate, and distribution coefficient / desorption rate of a chemical substance whose antifouling activity is to be determined. By finding one, the antifouling activity of the chemical substance can be easily and efficiently estimated.

From FIG. 2 to FIG. 5, the chemical substance whose antifouling activity is to be determined shows that the sorption rate is 100 to 2000 mg / min.
A chemical with a desorption rate of 10 to 1500 mg / min, a distribution coefficient / sorption rate of 0.3 to 80 and a distribution coefficient / desorption rate of 0.3 to 200 may have good antifouling activity. Therefore, compounds having antifouling activity can be efficiently screened by selecting chemical substances meeting these criteria.

[0051]

The method for estimating the antifouling activity of a chemical substance and the method for screening a compound having an antifouling activity according to the present invention are as described above.
The compound can be evaluated easily and in a short time, and a compound having an antifouling activity can be efficiently selected from a large number of chemical substances.

[Brief description of the drawings]

FIG. 1 is a schematic diagram of a measurement chart of an oscillation frequency of a crystal oscillator.

FIG. 2 is a graph showing the relationship between the antifouling activity of the antifouling agent measured in Example 1 and the sorption speed on a lipid membrane. The vertical axis represents the logarithm of the antifouling activity (days), and the horizontal axis represents the sorption rate (mg / mg / day).
Min) logarithm.

FIG. 3 is a graph showing the relationship between the antifouling activity of the antifouling agent measured in Example 1 and the rate of desorption to the lipid membrane. The vertical axis is the logarithm of the antifouling activity (days), and the horizontal axis is the desorption rate (mg / mg).
Min) logarithm.

FIG. 4 is a graph showing the relationship between the antifouling activity of the antifouling agent measured in Example 1 and the distribution coefficient / sorption rate. The vertical axis is the logarithm of the antifouling activity (days), and the horizontal axis is the logarithm of distribution coefficient / sorption rate.

FIG. 5 is a graph showing the relationship between the antifouling activity of the antifouling agent measured in Example 1 and the distribution coefficient / desorption rate. The vertical axis is the logarithm of the antifouling activity (days), and the horizontal axis is the logarithm of distribution coefficient / desorption rate.

FIG. 6 is a graph showing the relationship between the antifouling activity of the antifouling agent measured in Example 1 and the partition coefficient for a lipid membrane. The vertical axis is the logarithm of the antifouling activity (days), and the horizontal axis is the logarithm of the distribution coefficient.

Claims (10)

[Claims] 1. A chemical substance whose antifouling activity is to be determined is added to water immersed in a crystal oscillator coated with a lipid membrane, and then water around the crystal oscillator is replaced with water not containing the chemical substance. The change in the oscillation frequency of the crystal oscillator during the period from the addition of the chemical substance to the oscillation frequency of the crystal oscillator after the replacement with water containing no chemical substance until the oscillation frequency of the crystal oscillator becomes stable, A characteristic corresponding to the change of the oscillation frequency is obtained by observing with a frequency measuring device, and the antifouling activity of the chemical substance is estimated from a relationship between the antifouling activity and the characteristic obtained in advance. A method for estimating the antifouling activity of chemical substances. 2. The method according to claim 1, wherein the lipid membrane is an ion complex type synthetic bilayer membrane of dioctadecyldimethylammonium salt and polystyrenesulfonic acid. 3. The characteristic corresponding to the change of the oscillation frequency is a sorption rate of the chemical substance to the lipid membrane, which is derived from a rate of decrease of the oscillation frequency generated after the addition of the chemical substance.
3. The method according to claim 1, wherein the predetermined relationship is a negative correlation between the antifouling activity and the sorption rate. 4. A characteristic corresponding to a change in oscillation frequency, wherein the chemical substance is derived from a rate of increase in oscillation frequency that occurs after water surrounding the crystal oscillator is replaced with water not containing the chemical substance. 3. The method according to claim 1, wherein the rate of desorption from the lipid membrane is a negative correlation between the antifouling activity and the desorption rate. 4. 5. The characteristic corresponding to the change of the oscillation frequency includes a partition coefficient of the chemical substance to the lipid membrane in the lipid membrane-water system, which is derived from a decrease in the oscillation frequency generated after the addition of the chemical substance. It is the ratio of the sorption rate of the chemical substance to the lipid membrane derived from the rate of decrease of the oscillation frequency generated after the addition of the substance, and the relationship obtained in advance is a positive correlation between the antifouling activity and the ratio. The method according to claim 1 or 2, wherein 6. The characteristic corresponding to the change in the oscillation frequency includes a partition coefficient of the chemical substance to the lipid membrane in the lipid membrane-water system, which is derived from a decrease in the oscillation frequency generated after the addition of the chemical substance, and the quartz crystal. It is the ratio of the chemical substance to the desorption rate from the lipid membrane, which is derived from the rate of increase in the oscillation frequency that occurs after replacing the water around the oscillator with the water that does not contain the chemical substance. The method according to claim 1 or 2, wherein the ratio is a positive correlation between the antifouling activity and the ratio. 7. The method according to claim 3, wherein an ionic complex type synthetic bilayer membrane of dioctadecyldimethylammonium salt and polystyrenesulfonic acid is used as the lipid membrane, and the sorption rate is 100 to 2000 mg / min. A method for screening a compound having an antifouling activity, which comprises selecting a substance. 8. A chemical substance having a desorption rate of 10 to 1500 mg / min according to the method of claim 4, wherein an ion complex type synthetic bilayer membrane of dioctadecyldimethylammonium salt and polystyrene sulfonic acid is used as the lipid membrane. A method for screening a compound having antifouling activity, characterized by selecting 9. The method according to claim 5, wherein an ionic complex type synthetic bilayer membrane of dioctadecyldimethylammonium salt and polystyrenesulfonic acid is used as the lipid membrane, and the chemical substance in the lipid membrane-water system is applied to the lipid membrane. A method for screening a compound having an antifouling activity, wherein a chemical substance having a ratio between a partition coefficient and a sorption rate of 0.3 to 80 is selected. 10. The method according to claim 6, wherein an ionic complex type synthetic bilayer membrane of dioctadecyldimethylammonium salt and polystyrenesulfonic acid is used as the lipid membrane, and the chemical substance in the lipid membrane-water system is applied to the lipid membrane. A screening method for a compound having an antifouling activity, wherein a chemical substance having a ratio between a partition coefficient and a desorption rate of 0.3 to 200 is selected.