JP2000281581A - Production of purified propolis extracted solution from which insoluble ingredient is removed and purified propolis extracted solution from which insoluble ingredient is removed - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a purified propolis extracted solution from which an insoluble ingredient which is drinkable, safe and readily treatable and obtain a purified propolis extracted solution. SOLUTION: This method for producing the propolis extracted solution comprises a step for pouring a propolis extracted stock solution obtained by extracting propolis with ethanol into a gel permeation chromatographic device using a column in which a prescribed gel is packed, a step for separating each component in the poured propolis extracted stock solution from the column by using ethanol as an eluent and a step for recovering an elute eluted after a prescribed time among the elute separated by the above step and eluted from the column as a purified propolis extracted solution from which an insoluble ingredient is removed.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for separating and removing insoluble components from a purified propolis extract from which insoluble components have been removed, in particular, a propolis extract stock solution extracted with ethanol, to remove stable and highly safe insoluble components. The present invention relates to a method for producing a purified propolis extract, a purified propolis extract from which insoluble components have been removed, and the like.

[0002]

2. Description of the Related Art Propolis is a resin-like (animal-like) substance produced by mixing the viscous resin of a tree collected by a bee from various plants with the body fluid secreted by a bee. Devour. Propolis generally contains 50 to 55% of resin and glue and 25 to 40% of wax in addition to active ingredients including flavonoids.
Propolis contains few nutrients such as royal jelly, such as carbohydrates, proteins, vitamins, and minerals, but instead contains many chemical substances having pharmacological actions. For this reason, propolis
It is attracting attention as a substance having an antibacterial action, an antioxidant action, an anti-inflammatory action, a local anesthetic action, an immunomodulating action, and the like. These effects are considered to be exerted by various components such as flavonoids, aromatic carboxylic acids, and aromatic aldehydes contained in propolis.

[0003] Since this propolis has no umami component, it is hardly taken as it is, and various processes are performed, and it is generally distributed as a processed propolis product or a propolis derivative. At the time of processing, an active ingredient containing a flavonoid or the like is usually extracted from propolis (propolis extract), but at the time of extraction, ethanol or a mixed solution of ethanol and purified water is mainly used as an extract (solvent).

[0004]

However, when ethanol (or a mixed solution of ethanol and purified water) is used as a solvent, it is not effective for components such as wax which may be difficult to drink, or for resin or glue. Components also dissolve into the solvent. Therefore, a propolis extract subjected to “indiscriminate extraction” is generally used. Also, for wax,
Resins and glue are essentially insoluble components, which often adhere to and adhere to pipes of processing equipment or vessel walls due to changes in concentration or temperature during processing of propolis extract. The treatment of the attached insoluble component is difficult, and the processing of propolis is not easy. Further, there is a problem that insoluble components adhere to the container even during storage of the product. Therefore, it is not easy to increase the concentration of the propolis extract, and thus the concentration of the active ingredient. For this reason, there is a propolis extract processed product in which an emulsifier or a surfactant is added to emulsify and disperse a resin or the like, thereby facilitating handling during processing or the like.

However, the propolis extract containing resin, glue, and wax has been reported to cause allergic eczema in the past, and it is safe to use as a health supplement (health food), cosmetics, cosmetics, etc. There are difficulties in terms of.
Further, Japanese Patent Application Laid-Open No. 5-59391 discloses a propolis extract purified using supercritical CO _2. However, in supercritical extraction, it is necessary to handle a high-pressure gas. And cost issues. Further, there is a problem that the target component cannot be sufficiently extracted by the supercritical extraction. An object of the present invention is to provide a method for producing a purified propolis extract, which is easy to drink, is safe, and has easy-to-handle and removes insoluble components, and a purified propolis extract.

[0006]

Means for Solving the Problems The inventors of the present invention remove the resin, glue, and wax which are insoluble components contained in ethanol-extracted propolis, and extract only the active ingredient.
Various experiments were performed. Then, they have found that the above-mentioned problem is solved by performing gel permeation chromatography using a column filled with a predetermined gel.

More specifically, the method for producing a propolis extract from which insoluble components have been removed according to the present invention comprises the steps of (1) gel permeation chromatography using a propolis extract stock solution obtained by extracting propolis with ethanol using a column filled with a predetermined gel. A step of injecting into the device, (2) a step of separating each component in the injected propolis extract stock solution by the column using ethanol as an eluent, and (3) an eluate separated by the step and eluted from the column. And recovering, as a purified propolis extract from which insoluble components have been removed, a substance eluted after a predetermined time (claim 1). According to this, each component contained in the propolis extraction stock solution extracted with ethanol (or a mixed solution of ethanol and purified water) can be separated depending on the difference in molecular size. That is, since the components composed of small molecules are small in size, they penetrate deeply into the pores of the gel and are retained on the column for a long time. On the other hand, since the component composed of a large molecule has a large size, it cannot penetrate deeply into the pores, and the time for which the component is retained in the column is short. In the present invention, the insoluble components such as the wax component and the resin component in the propolis are composed of large molecules and elute from the column earlier. On the other hand, an active ingredient such as a flavonoid is composed of a small molecule, and is held in a column for a long time to elute. Therefore, each component in the propolis extraction stock solution is separated by the retention time (retention time) retained in the column, and elutes from the column in order of larger molecules. Therefore, by collecting the eluate eluted from the column after a predetermined time, a purified propolis extract from which insoluble components have been removed can be obtained.

Further, the gel used in the method for producing a purified propolis extract from which the insoluble components have been removed is prepared by using hydroxyethyl methacrylate.
It is a fully porous gel having a predetermined diameter in which a diol group is introduced into rylate) by a chemical bond (claim 2). The gel is porous not only on the surface but also on the whole particles of the gel. Therefore, there is a feature that the sample load is large, and a column with a small theoretical plate height and high efficiency can be constructed. Furthermore, by introducing diol groups into the gel, the interaction between the gel and each component in the propolis extract stock solution can be kept low, and each component in the propolis extract stock solution can be more reliably separated for each molecular size. can do.

Furthermore, the present invention is a purified propolis extract from which insoluble components have been removed produced by the method for producing a propolis extract from which insoluble components have been removed according to claim 1 or claim 2 (claim 3). . The purified propolis extract from which the insoluble components have been removed is suitable for taking and drinking and processing and products because it is an insoluble component and the wax components and ineffective resin components that cause intractability are removed. Is also easy to handle.

The present invention proposes a gel for producing a purified propolis extract, wherein a diol group is introduced into a totally porous hydroxyethyl methacrylate by chemical bonding (claim 4). This gel is made by introducing epoxy groups into hydroxyethyl methacrylate.

[0011]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below with reference to the drawings. FIG. 1 is a block diagram of a gel permeation chromatograph used in the production method of the present invention. FIG. 2 is a diagram illustrating the principle of separation by gel permeation chromatography.

{Description of the structure and function of the gel permeation chromatograph apparatus} The gel permeation chromatograph apparatus A (hereinafter referred to as “G”) used in the method of the present invention.
As shown in FIG. 1, an eluent tank 1, a stock tank 2, a liquid feed pump 3, an automatic injector 4,
It is composed of a column 5, a column thermostat 6, etc.

The eluent tank 1 is a container for storing the eluent. The eluent plays the role of a mobile phase in gel permeation chromatography (hereinafter, “GPC”). The eluent must have properties such as not causing a chemical reaction with the components contained in the propolis extract stock solution and the gel 5b as a fixed layer described later, and dissolving each component contained in the propolis extract stock solution well. It is. In the present invention, ethanol is used as an eluent in consideration of safety and easy handling of the eluent after use.

The stock tank 2 stores a propolis extraction stock solution extracted with ethanol (or a mixed solution of ethanol and purified water). The liquid sending pump 3 sends the eluent to the column 5 at a predetermined flow rate. The liquid feed pump 3 is required to have little pulsation, to be able to feed the liquid with high accuracy, to be able to adjust the flow rate, to have chemical resistance, and the like. The automatic injector 4 injects the propolis extract into the GPC device A. The auto-injector 4 is required to prevent the propolis extract stock solution from flowing back when the propolis extract stock solution is injected into the GPC apparatus A, and to be able to inject a predetermined amount of the propolis extract stock solution.

The column 5 is composed of a chromatographic tube 5a as a main body and a gel 5b as a fixed layer filled therein. The chromatographic tube 5a is made of stainless steel or the like because a material having excellent pressure resistance and chemical resistance is required.

The gel 5b separates each component dissolved in the stock solution of propolis extraction for each molecular size (apparent size). The gel 5b forms a main part of the GPC apparatus A and has a network structure having many pores. In addition, GPC
Performs the separation of the components by utilizing the fact that the components contained in the propolis extract stock solution are retained differently with respect to the pores of the gel 5b. That is, as shown in FIG. 2A, the small molecule Sm penetrates deeply into the pores of the gel 5b, so that it takes time to pass through the column 5 (retention time is long). On the other hand, since the large molecule Lm cannot enter the pores of the gel 5b or can enter only shallowly, the time of passing through the column 5 is short (retention time is short). As a result, each component contained in the sample solution subjected to GPC is separated for each molecular size, and elutes from the column 5 in order from the component consisting of the large molecule Lm (see FIG. 2 (b)). Specifically, in the propolis extraction stock solution as a sample solution, the insoluble components such as wax, resin, glue, etc. are composed of large molecules Lm, so that the retention time is short and elutes from the column 5 quickly. On the other hand, an active ingredient such as a flavonoid is composed of small molecules Sm, and thus has a long retention time and stays in the column 5 for a long time.

The gel 5b used for GPC basically has no interaction with each component contained in the propolis extract stock solution. This is because if an interaction occurs, components cannot be separated depending on the molecular size. For this reason, it is preferable to introduce a hydrophilic functional group into the gel 5b.
As the hydrophilic functional group, a diol group such as glycol or glycid is suitable.

The gel 5b has not only the surface thereof but also the gel 5b.
All-porous gels with pores inside are suitable. This is because the total porous gel has a large surface area as compared with the superficially porous gel, so that the sample load is large. Further, the number of theoretical plates is small, and an efficient column 5 can be formed. The size of the gel 5b is spherical with a diameter of about 2 to 30 μm. By the way, 30 μm in which a diol group is introduced into hydroxyethyl methacrylate by a chemical bond.
In the case of a totally porous gel 5b having a diameter, the range of the molecular weight that can be processed is about 1 × 10 ² (100) to 1 × 10 ⁴ (10,000). The diol group can be introduced by epoxidizing the raw material and introducing the epoxy group, and then diolating the epoxy group portion. A conventionally known technique can be applied to this operation.

The column thermostat 6 keeps the temperature of the column 5 constant. This is because when the temperature of the column 5 changes, the retention time differs. The detector 7 is provided for detecting and measuring components in the eluate eluted from the column 5. As the detector, an absorbance detector, a differential refractometer, or the like can be used. The absorbance detector is a method utilizing the light absorption of a chemical substance, and is suitable for those having light absorption from the ultraviolet to the visible region. The differential refractometer is a method that utilizes the difference in light refractive index between an eluate eluted from the column 5 and an eluent to be used as a control, and can detect any chemical substance. The measured value of the detector 7 is sent to a system controller 13 described later, and displayed on a monitor and a recorder (not shown) of the system controller 13 as a chromatogram shown in FIG.

The flow path switching device 8 switches the flow path of the eluate that has passed through the detector 7. The switching of the flow path is performed by a command of the system controller 13 based on a chromatogram or the like which is a measurement value of the detector 7 (see FIG. 3). The symbol F1 shown in the chromatogram of FIG.
The eluate eluted from the column 5 in the first time zone, which is the eluate itself that does not contain each component in the propolis extract stock solution. The symbol F2 is an eluate eluted from the column 5 in the next time zone, and contains components composed of large molecules such as wax and resin, and hardly contains components composed of small molecules such as flavonoids. The symbol F3 is an eluate eluted from the column 5 in the last time zone, contains an active ingredient composed of small molecules such as flavonoids, and hardly contains components composed of large molecules such as wax.

The waste liquid tank 9 stores the eluate F2 as a waste liquid. The storage tank 10 collects and stores the eluate F3 as a purified propolis extract. The concentrator 11 concentrates the eluate F3 to increase the concentration of an active ingredient such as a flavonoid. The storage tank 12 stores the eluate F3 concentrated by the concentrator 11 as a concentrated and purified propolis extract. The purified propolis extract and the concentrated purified propolis extract stored in the storage tanks 10 and 12 are the propolis extracts of the present invention from which insoluble components have been removed.

Next, each flow path will be described. The flow path R connects the flow path switch 8 to the eluent layer 1 and returns the eluent F1 to the eluent layer 1 as an eluent. The flow path W connects the flow path switch 8 and the waste liquid tank 9 and guides the eluate F2 (waste liquid) to the waste liquid tank 9. The flow path N connects the flow path switching device 8 and the storage tank 10, and the eluate F3
(Purified propolis extract) is led to the storage tank 10. Channel C
When the eluate F3 (purified propolis extract) is concentrated, the eluate is guided to a concentrator. And the flow path S
Leads the concentrated eluate F3 (concentrated and purified propolis extract) to the storage tank 12.

Finally, the system controller 13
The PC device A is totally controlled. Specifically, control of the amount of liquid supplied by the liquid pump 3, control of the injection interval of the automatic injector 4, control of the temperature of the column thermostat 6, and control of the flow path switch 8 based on the measurement value of the detector 7 For example, the flow path is switched.
As described above, the separation state of each component in the propolis extract stock solution by the column 5 is measured by the detector 7, and is monitored by a monitor and a recorder (not shown) of the system controller 13.
It is displayed as the chromatogram shown in FIG. Further, the system controller 13 controls the flow path switching device 8 and the like based on the measured value of the detector 7 and the pattern of the chromatogram (see FIG. 3) obtained in advance.

<< Description of Separation Method >> In the present invention, first, a propolis extraction stock solution extracted with ethanol or a mixed solution of ethanol and purified water is injected into a GPC apparatus A using a column 5 packed with a predetermined gel 5b (FIG. 1). The injection amount is appropriately determined according to the flow rate of the eluent, the type of the gel 5b, the size of the column 5, and the like. The propolis extract stock solution to be injected is prepared by adding an appropriately sized propolis mass to ethanol or a mixture of ethanol and purified water and stirring the mixture. As described above, since extraction with ethanol or the like is a non-discriminatory extraction, the propolis extract stock solution contains components having pharmacological actions such as flavonoids, components such as wax that cause intractability, resins and glue. Ineffective components such as quality are included (all are insoluble components). Incidentally, an object of the present invention is to remove insoluble components from the propolis extract stock solution and increase the concentration of the active components.

The injected propolis extract stock reaches the column 5 according to the flow of the eluent. Gel 5 in column 5
b), and the gel 5b separates each component in the propolis extract stock solution by molecular size according to the principle described above (see FIG. 2 (b)). In the case of the present invention, the insoluble component consisting of the large molecule Lm elutes from the column 5 quickly,
The active ingredient composed of the small molecule Sm penetrates deep into the pores of the gel 5b and elutes from the column 5 later than the insoluble component.

The order in which the components are eluted from the column 5 after the injection of the propolis extract stock solution will be described with reference to FIG. FIG. 3 is a chromatogram when insoluble components are separated by the production method of the present invention. (1) First, the eluent F1 eluted from the column 5 in the first time zone is the eluent itself. Since the eluent F1 can be reused as an eluent, it can be returned to the eluent tank 1 through the flow path R by the flow path switch 8. In addition,
In order to stabilize (equilibrate) the column, the eluent is flowed at a constant flow rate in the GPC apparatus A prior to injection of the propolis extraction stock solution.

(2) In the next time zone, the eluate F2 containing the insoluble component elutes. The eluate F3 containing the insoluble component is stored as waste liquid in the waste liquid layer 9 through the flow path W by the flow path switching device 8. The waste liquid can be reused as an eluent by a treatment such as distillation.

(3) In the last time period, the eluate F3 containing an active ingredient such as flavonoids elutes. The eluate F3 containing the active ingredient was used as a purified propolis extract.
The liquid is stored in the storage tank 10 through the flow path N by the flow path switching device 8. Further, the purified propolis extract is led to the concentrator 11 through the flow path C by the flow path switch 8 and concentrated for the purpose of concentration. The concentrate is stored in the storage tank 12 as a concentrated and purified propolis extract. The purified propolis extract and the concentrated purified propolis extract are provided for processing into health supplements, cosmetics, and the like.

By the way, the switching of the flow path by the flow path switch 8 is performed when conditions such as the composition of the eluent, the flow rate of the eluent, the size of the column 5, the type of the gel 5b, and the temperature of the column thermostat 6 are constant. Since the elution time zone (retention time) of each component is always constant, it can be switched by a timer. Further, the switching can be performed based on the measurement value of the detector 7.

The eluate eluted from the column 5 after the eluate F3 containing an active ingredient such as a flavonoid elutes is the eluent itself. This eluate can be returned to the eluate tank 1 through the flow path R by the flow path switch 8 for reuse.

After the injection of one undiluted propolis solution is completed, the GPC apparatus A can inject the next undiluted propolis extract solution and repeat the cycle of injection, separation, and recovery. At this time, if the interval (injection interval) between the injection of one cycle and the injection of the next cycle is short, the eluate F3 containing the active ingredient of one cycle and the eluate F2 containing the insoluble component of the next cycle are separated. Care must be taken with the infusion interval as they will come together and mix. Incidentally, the longer the injection interval, the lower the processing capacity. The GPC apparatus A may be a system in which a plurality of columns 5 are provided and the injection flow path from the automatic injector 4 can be switched so that a plurality of chromatographic operations are performed in parallel. This is because the injection interval can be shortened while the devices are shared, and the processing capacity can be increased.

[0032]

Next, the present invention will be described in more detail with reference to examples (see FIG. 1 and the like). Note that the present invention is not limited to this embodiment. Embodiment 1 In this embodiment, the GPC device A has an inner diameter of 8
A column 5 having a length of 0 mm and a length of 1500 mm was used. The column 5 is mounted on a column thermostat 6 set at a temperature of 35 ° C. The column 5 is filled with a 30 μm gel 5b in which a diol group is introduced into a totally porous hydroxyethyl methacrylate by a chemical bond. As the detector 6, a differential refractometer detector was used.

Prior to the injection of the propolis extract stock solution, first, in order to equilibrate the GPC apparatus A, the eluent is continuously supplied from the eluent tank 1 to the column 5 at a flow rate of 350 ml / min by the liquid sending pump 3. The temperature of the column thermostat 6 and the flow rate of the liquid sending pump 3 are controlled by the system controller 13. The flow of the eluent at this time is in the order of the eluent tank 1 → the liquid sending pump 3 → the column 5 → the detector 7 → the flow path switching device 8 → the flow path R → the eluent tank 1. Used. This operation is performed for about 15 to 20 minutes to equilibrate the GPC apparatus A. Completion of the equilibrium is determined by the system controller 13 based on the measured value of the detector 7 and displayed on a monitor (not shown) of the system controller 13.

When the equilibration is completed, the propolis undiluted solution stored in the stock tank 2 is automatically injected into the system of the GPC apparatus A by the automatic injector 4. The injection volume is 15
0 ml. The injected propolis extract stock solution reaches the column 5 together with the eluent, and is separated into components in the column 5 based on the molecular size. The principle of this separation is as described above.

The separation state is measured by the detector 7 and based on the measured value, the system controller 13
And the eluate F3 was collected in the storage tank 10 as a purified propolis extract. The eluent F1 was returned to the eluent tank 1 and the eluent F2 was led to the waste tank 9 according to a command from the system controller 13.

Then, the purified propolis extract collected in the storage tank 10 was again injected into the GPC apparatus A by the automatic injector 4, and it was confirmed whether insoluble components were separated and removed.
FIG. 4 shows the chromatogram at this time.
7% had been separated off.

Here, a simple test was performed to compare the degree of removal of insoluble components. That is, the purified propolis extract of the present invention and a commercially available propolis extract were each taken into a dropper (both ethanol extracts) and dropped into a beaker containing a sufficient amount of water. Both concentrations are the same at 20 w / v%. Then, a film of insoluble components formed on the surface of water was scooped with a polystyrene rod, and the amount was measured. The film of the insoluble component is formed on the surface because the concentration of ethanol is reduced by being dropped into water, and the component which has been dissolved in ethanol until now becomes insoluble. As a result, in the case of the purified propolis extract of the present invention, almost no insoluble component film was formed, and measurement was not possible. On the other hand, in the case of a commercially available propolis extract, a film of a remarkably insoluble component was formed, and the amount thereof was 40 to 50% with respect to the above 20 w / v% of 20 w.
As described above, according to the present invention, almost no insoluble components in the propolis stock solution can be removed. Therefore, the purified propolis extract of the present invention is extremely easy to handle during secondary processing.

The present Example 1 relates to a gel 5b in which a diol group is introduced into a totally porous hydroxyethyl methacrylate by chemical bonding, but the present invention is not necessarily limited to this gel 5b. Instead, the insoluble components can be separated (removed) by other gels, for example, porous silica gel, styrene-based gel or methyl methacrylate gel into which diol groups are respectively introduced. However, the separation ability for separating the insoluble component and the active component is most excellent in a gel in which a diol group is introduced into a totally porous hydroxyethyl methacrylate by a chemical bond.

Example 2 The purified propolis extract prepared in Example 1 from which insoluble components such as wax were removed and the unpurified unprocessed propolis extract were subjected to a 48 hour closed patch test as a safety test on human skin. A primary irritation test was performed. In the test, two types of 15% blended petrolatum ointment were prepared by mixing propolis extract with petrolatum and used. Vaseline was used directly as a control. The test has 20 subjects.

As can be seen from the test results shown in FIG. 5, it was confirmed that there was a clear difference between the propolis extract stock solution and the purified propolis extract solution of the present invention.
The table shown in FIG. 5B is obtained by processing the data of the table shown in FIG.

[0041]

As described above, according to the method for producing a purified propolis extract from which insoluble components have been removed according to the present invention, the insoluble components such as wax, glue, resin and the like contained in the propolis extract stock solution can be reliably obtained. Active ingredients such as flavonoids can be separated. Therefore, a purified propolis extract from which insoluble components of good quality have been removed can be produced. Further, according to the gel 5b of the second aspect, the processing capacity of the GPC device A can be increased. The purified propolis of the present invention from which insoluble components have been removed can be used for propolis processing without the insoluble components such as resin components adhering to the pipe wall of a processing device, for example, when manufacturing a propolis processed product such as a health supplement. Products and propolis derivatives are easier to manufacture. Further, even when the purified propolis is stored, no resin component or the like adheres to the wall of the storage container. Further, the purified propolis of the present invention from which the insoluble component was removed was able to enhance safety because it had low irritation to the skin. From this, the application to health foods, cosmetics, cosmetics, and the like can be broader.

[Brief description of the drawings]

FIG. 1 is a block diagram of a gel permeation chromatograph used in the production method of the present invention.

FIG. 2 is a principle diagram of separation by gel permeation chromatography. (A) is a figure which shows the principle of separation by a gel, (b) is a figure which shows a separation state with time.

FIG. 3 is a chromatogram at the time of separating insoluble components according to the production method of the present invention.

FIG. 4 is a chromatogram of a purified propolis extract of the present invention from which insoluble components have been removed.

FIG. 5 is a table showing the results of a human skin primary irritation test by a closed patch test of a purified propolis extract from which insoluble components have been removed according to the present invention. (A) is a table showing closed patch test results, and (b) is a table showing average evaluation points.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 Eluent tank 2 Stock tank 3 Liquid sending pump 4 Automatic injector 5 Column 5a Chromatographic tube 5b Gel 6 Column constant temperature bath 7 Detector 8 Channel switch 9 Waste liquid tank 10 Storage tank (for purified propolis extract) 11) Concentrator 12 Storage tank (for concentrated and purified propolis extract) 13 System controller A Gel permeation chromatograph (G
PC device) R, W, N, C, S... Channel Lm Large molecule (insoluble component such as wax) Sm Small molecule (active component such as flavonoid) F1, F2, F3.

Claims (4)

[Claims] 1. A step of injecting a propolis extract stock solution obtained by extracting propolis with ethanol into a gel permeation chromatograph using a column filled with a predetermined gel, wherein each component in the injected propolis extract stock solution is ,
A step of separating the eluate from the column separated by the step and eluted after a predetermined time, and recovering a purified propolis extract from which insoluble components have been removed, A method for producing a purified propolis extract from which insoluble components have been removed. 2. The gel according to claim 1, wherein the gel is a gel having a predetermined diameter in which a diol group is introduced into a totally porous hydroxyethyl methacrylate by a chemical bond.
3. A method for producing a purified propolis extract from which insoluble components have been removed according to 1 .. 3. A purified propolis extract from which insoluble components have been removed produced by the method for producing a propolis extract from which insoluble components have been removed according to claim 1 or 2. 4. A gel used for removing insoluble components from a propolis stock solution obtained by extracting propolis with ethanol, wherein a diol group is introduced into a totally porous hydroxyethyl methacrylate by a chemical bond. Gel for producing purified propolis extract.