JPH0329441B2 - - Google Patents

Description

[Detailed description of the invention]

"Industrial Application Field" The present invention utilizes the selective and reversible formation and decomposition of certain clathrate compounds in supercritical gas or high-pressure liquefied gas to extract target components from a mixture with high purity. , relates to a method for separation with high yield. ``Prior art'' Separation methods that utilize the selective formation of clathrate compounds have been widely used in laboratories; It is difficult to efficiently isolate mixtures. For example, using methanol as a solvent,
The separation of highly unsaturated fatty acid-rich mixtures from natural fats and oils by the urea addition fractionation method, which involves crystallization, filtration, washing, and solvent separation in the solution, is also carried out industrially; It is difficult to isolate the components. In other words, each time the clathration operation is repeated, the difference in the stability of the clathrate compounds in the adduct or non-adduct becomes gradually smaller, and not only does efficient isolation become impossible, but also It cannot be avoided that the inclusion operation is extremely complicated. For example, in the urea addition fractionation method using a urea-saturated methanol solution, the adduct is crystallized and filtered out in one operation, and the non-adduct is separated from the filtrate and dissolved in methanol and the filtrate for concentration. Removal of urea is required. Also,
A method of separating unsaturated fatty acids using solid urea as an inclusion lattice component and aliphatic hydrocarbons or alicyclic hydrocarbons as a solvent has also been proposed (Japanese Patent Application Laid-open No. 164196/1982), but Although the step of removing urea from the process is omitted, it is still complicated to perform multiple operations on an industrial scale. On the other hand, supercritical gas extraction method (Special Publication No. 54-10539)
is also known, but with this extraction method, for example, it is relatively easy to separate constituent fatty acids based on differences in the number of carbon atoms, but it is difficult to separate fatty acids with the same number of carbon atoms but different numbers of double bonds. As such, the separation performance of components with similar structures is low, and its practical range is limited. "Problems to be Solved by the Invention" Here, the present inventors have solved the problem by solving the following problems:
As a result of various studies on the efficient separation of desired components, we have found that using supercritical gas or high-pressure liquefied gas as a solvent for inclusion reactions is extremely difficult using conventional simple inclusion fractionation methods or supercritical gas extraction methods. The ability to separate target components with high purity and high yield even from components with similar structures,
The separation process is simplified because the solute and solvent can be separated extremely easily, which is a characteristic of supercritical fluids.
Since the solvent is the same as supercritical fluid extraction,
We obtained the knowledge that surprising features such as high consistency with the process appeared, and completed the following invention. "Means for Solving the Problem" That is, the present invention obtains an extraction phase from a mixture using a supercritical gas or a high-pressure liquefied gas as a solvent, and uses this extraction phase as a medium to prevent the formation of clathrate compounds. If the degree of activation is low, an entrainer having the ability to activate inclusion formation is coexisting therein, and pressure and temperature are used as operating factors to cause the inclusion lattice components to react with the solute components in the extraction phase. Supercritical gas or high-pressure liquefaction is used to obtain an extraction phase consisting of the desired solute component by selectively and reversibly forming and decomposing clathrate compounds, and then separating the solvent component gas to obtain the desired solute component. This paper aims to provide a clathrate separation method using gas as a medium. The selectivity in the formation of clathrate compounds is due to the shape of the gaps unique to the crystal structure of the host molecule, which is an inclusion lattice component. This crystal structure may be newly formed due to the presence of a guest molecule incorporated into the inclusion lattice, or may exist stably regardless of the guest molecule. A typical example of the former is urea, and a typical example of the latter is zeolite, an adsorbent with shape selectivity. Also,
As a condition for the formation of the clathrate compound to be reversible, it is desirable that the interaction between the host molecule and the guest molecule be based on a physical bond, such as a van der Waals force or a hydrogen bond. Table 1 shows the generally known host-guest molecule relationships.

[Table] Now, regarding the formation and separation of clathrate compounds,
In order to impart selectivity and reversibility of the bond between host-guest molecules according to the purpose, the selection of a solvent is particularly important. By using supercritical gas or high-pressure liquefied gas, which has affinity with the mixture to be separated and has the effect of activating the inclusion reaction, high purity and high yield, which were impossible with conventional methods, can be achieved. This makes it possible to separate the rates. That is, it has been discovered that supercritical gas or high-pressure liquefied gas near the critical point has low viscosity and high permeability, and these properties work advantageously for the formation of clathrate compounds, which are heterophasic reactions. However, in exceptional cases where certain types of supercritical gases or high-pressure liquefied gases activate the formation of clathrate compounds to a particularly low degree, the clathrate reaction will not proceed smoothly; It has also been found that activation of the formation of clathrate compounds can be promoted if a relatively small amount of an entrainer having the ability to activate clathrate formation is allowed to coexist, if necessary. Equilibrium reactions for the formation of clathrates sensitively follow temperature, which is a controlling factor, in supercritical gas or high-pressure liquefied gas phases, and the equilibrium shifts from clathrate formation to decomposition in a relatively short time by increasing temperature. be able to. In this case, since the solvent capacity of the supercritical gas or high-pressure liquefied gas depends largely on pressure, by selecting an appropriate pressure, sufficient solvent capacity can be maintained in the temperature range from package formation to decomposition. From the above, as shown in the examples of the present invention,
The target components can be concentrated and recovered using extremely simple equipment and methods. Note that the solvent is not limited to pure components, and the separation ability can be improved by changing the composition of the mixed solvent. The inclusion lattice component is not limited to one type, and a combination of multiple types may be used, especially when it is necessary to increase the separation ability of the target component. According to the method of the present invention, the separation of the target component and the solvent is carried out quickly due to the reduction in pressure, the residual amount of solvent in the product is extremely small, and almost complete recovery is possible. It has the great advantage of being much more energy efficient than other separation methods. Furthermore, the dissolution of the clathrate lattice components into the supercritical gas or high-pressure liquefied gas phase is extremely small and can be ignored, and the guest components in the clathrate compound are quickly entrained in the solvent gas after decomposition. An advantage is that the lattice components can be used repeatedly as they are. Furthermore, it is also possible to combine the method of the present invention with a reflux method that takes advantage of the difference in solvent capacity due to changes in the temperature and pressure of supercritical gas or high-pressure liquefied gas. It is also possible to use it in combination with a filtration membrane method or a reverse osmosis membrane method, and in this case, the pressure of the system can be used as is as the driving force for separation, making this a very advantageous combination. In the present invention, carbon dioxide and nitrous oxide are used as supercritical gases or high-pressure liquefied gases, urea and deoxycholic acid are used as inclusion lattice components, methanol is used as an entrainer, and fatty acids and fatty acid esters are used as mixture components. Although a specific example of inclusion/separation is shown, the present invention is not limited thereto, and the idea of the present invention can be applied to a wide range of combinations. In inclusion separation, by appropriately adjusting the temperature and pressure in the system, an extraction phase consisting of the desired solute components can be obtained over time under the flow of supercritical gas or high-pressure liquefied gas, but the target components and A conceptual diagram of concentration separation of other constituent components is shown in FIG. Here, a case where the target component forms the most unstable clathrate compound is taken as an example.
During the process, supercritical gas or high-pressure liquefied gas and lattice components are brought into countercurrent contact, and a temperature gradient is provided in the recovery section below the column where the contact occurs, so that most of the clathrate compounds are decomposed at the bottom of the column.
The upper concentration section of the column has a sufficient length and set temperature such that only the target components are present in the extraction phase at the top of the column.
Side cuts are taken at the point of maximum concentration of each component. In this case, by setting the first side cut position from the top in consideration of the pinch point of the target component, the target component can be obtained at a high recovery rate. The lattice components and supercritical gas or high pressure liquefied gas can be recycled and reused. In addition, a moving bed, a multistage fluidized bed, a pseudo moving bed, etc. can be selected as appropriate for the contact method of the column. Hereinafter, the present invention will be explained in more detail with reference to Examples. Example 1 Methyl esters of fatty acids obtained from fish oil
Separation was carried out using 16.0 g of supercritical carbon dioxide at 40° C. and 100 Kg/cm ² G as a solvent, and 104.7 g of urea micronized in a mortar as an inclusion lattice component. The separation device shown in FIG. 2 was used. First, predetermined amounts of raw materials and clathrate lattice components are charged into the raw material tank 5 and the clathrate compound forming tank 6, respectively, the constant temperature bath 10 and the pressure holding valve 11 are adjusted to predetermined temperatures and pressures, and the high-pressure pump 3 is operated. After the system reaches a predetermined pressure, the pressure reducing valve 7 is opened and the flow of supercritical gas is started. The pressurized carbon dioxide is in a supercritical gas state, dissolves soluble components in the raw material in the raw material tank 5, and is introduced into the clathrate compound forming tank 6. A part of the entrained solute component forms an clathrate compound with the inclusion lattice component in the tank 6, is separated from the extraction phase, and remains in the tank 6. The remainder is entrained by the supercritical gas and flows out from the tank 6. As mentioned above, the stability and formation rate of the formation of clathrate compounds vary depending on the types of inclusion lattice components (host molecules), solute components (guest molecules), and gases (solvent). Fractionation of solute components in the gas is performed. The pressure of the extraction phase flowing out of the tank 6 is reduced by a pressure reducing valve 7 and the solute is released into a collector 8, after which the flow rate is measured by a gas meter 9. In addition, the solute trapped in the collector 8 is sampled as appropriate, and its weight and composition are analyzed. Since this separation apparatus is of a semi-batch type, the solute concentration at the inlet of the clathrate compound forming tank 6 changes over time and becomes zero when all the soluble components in the raw material tank 5 have been extracted. Furthermore, if the supercritical gas continues to flow as a solvent, the unstable clathrate compound in the tank 6 will decompose, and eventually the solute will hardly flow out from the tank 6. At this point, the clathrate in tank 6 is stable, and in order to further rapidly decompose it, the clathrate equilibrium needs to be shifted. Methods for this include increasing the solubility of guest molecules in the extraction phase by increasing the pressure or changing the type or composition of the solvent, destabilizing the clathrate by increasing the temperature, and solubilizing the clathrate lattice components in the extraction phase. Furthermore, combinations of these methods are possible. In other words, the selection of a decomposition method should be made by considering operability and efficiency such as selective recovery of guest molecules, recovery of inclusion lattice components, and decomposition rate, but the most common method is , decomposition accompanied by temperature raising operation. Therefore, the clathrate compound is decomposed by increasing the pressure and temperature in the system while keeping the gas flowing. In addition, 1
is a gas cylinder, 2 is a cooler, and 4 is a heater. Some of the results are shown in Table 2 and Figures 3 and 4.
The runoff rate here refers to the ratio of outflow to the total amount of outflow (8.4g). The separation performance of fatty acid methyl esters having 20 carbon atoms (hereinafter abbreviated as C ₂₀ ) and 22 carbon atoms (hereinafter abbreviated as C ₂₂ ) in fish oil was examined. Fatty acid methyl esters with few double bonds form stable clathrate compounds in supercritical carbon dioxide, and in the entire flow area, eicosapentaenoic acid (hereinafter abbreviated as EPA or C _20-5 ) is the major component of the effluent. ), docosahexaenoic acid (hereinafter referred to as DHA)
Or abbreviated as C _22-6 . ) is the only methyl ester. Here, in the examples of the present invention, C _no represents a fatty acid or a derivative thereof having m carbon atoms and n double bonds. Note that the large change in the composition ratio in the effluent near the final effluent rate is due to the slight difference in separation performance due to the difference in the number of double bonds due to the fact that this device is a semi-batch type. This seems to be due to the fact that it was expanded. From the above, for mixtures with the same number of carbon atoms but with a large difference in the number of double bonds, if the recovery operation by decomposition of the clathrate compound is also used, it is possible to achieve a high recovery rate and a high purity separation method, which is extremely simple. , industrially applicable. This was done for comparison. In the supercritical gas extraction method, the composition ratio in the effluent is almost the same as the composition ratio in the charged raw material until near the final flow rate, and the separation performance is low.

【table】

[Table] Example 2 C ₁₈ with different numbers of double bonds by one as shown in Table 3
A mixture of ethyl esters of fatty acids was separated in a manner similar to Example 1. 7.0 g of the raw material mixture and 101 g of urea pulverized with a vibrating ball mill were used. The total flow rate was 2.5 g, which is 36% of the raw material. When little effluent is obtained,
When the clathrate compound was taken out of the system and decomposed using hot water, 4.3 g of clathrate decomposition product was obtained. Table 3 and FIG. 5 show the compositions of the effluent and clathrate decomposition products. It can be seen that the more double bonds there are, the higher the concentration ratio to the raw material composition, and by repeating the same operation on the effluent, it is possible to separate each component. Note that the phenomenon in which the composition of components with a large number of double bonds decreases with the outflow rate is due to the fact that the lattice components are not updated, and is not an essential problem. In the supercritical gas extraction method used for comparison, it is almost impossible to separate mixtures that have the same number of carbon atoms but differ in number of double bonds by one.

【table】

[Table] Example 3 Using the separation apparatus shown in Figure 2, methyl esters of fatty acids obtained from the fish oils shown in Table 4 were used as raw materials.
10.6g, 113.5g urea micronized in a vibrating ball mill
carbon dioxide per minute at 20°C.
0.3, and 3 per minute was used when increasing the temperature. The amount of effluent collected by the separator 8 was 9.6 g, which was about 91% of the raw material. Table 4 as well as FIG. 6 show the compositional changes in the effluent of the main components in the methyl esters of fatty acids obtained from fish oil. First, clathrate compounds were formed in high-pressure liquefied carbon dioxide at 20°C and 100 kg/cm ² G, and then,
Under these conditions, when almost no effluent could be obtained, the pressure was increased to 200 Kg/cm ² G, and the temperature was gradually raised to 80° C. to decompose the clathrate compound. It is generally known that urea clathrate compounds of fatty acids and their derivatives become more unstable as the number of carbon atoms decreases and as the number of double bonds increases. The behavior in the phase is also similar. That is, EPA and DHA, which are highly unsaturated fatty acids, do not stably form clathrate compounds with urea, and most of them flow out together with carbon dioxide during the formation of clathrate compounds. Also, small amounts of EPA, DHA
It can be seen that the clathrate compound decomposes rapidly at a fairly low temperature range. On the other hand, saturated fatty acids and unsaturated fatty acids with few double bonds form stable clathrate compounds with urea, and when clathrate compounds are formed, the composition ratio in the effluent is smaller than that in the raw material composition, and most of the clathrates are As they decompose, they flow out depending on their stability and concentration. Since this example is a semi-batch type, the inlet composition of the clathrate compound forming tank 6 changes over time and the clathrate lattice components are not updated, so the outflow composition changes in a seemingly complicated manner. The separation due to the difference in stability can be understood by comparing the effluent composition and the feed composition during clathrate formation and decomposition.

[Table] Example 4 Using the separation apparatus shown in Fig. 2, 109 g of urea pulverized with a vibrating ball mill was added to 10.2 g of fatty acid ethyl ester obtained from evening primrose seed oil as a raw material in the clathrate formation tank 6. Put the pressure of carbon dioxide
Formation of the clathrate compound was carried out at 100 Kg/cm ² G and a temperature of 25° C., and 4.9 g of effluent was obtained. After the formation of the clathrate compound, the pressure in the system was reduced to atmospheric pressure, and the urea adduct in the tank 6 was taken out and dissolved in warm water, yielding 5.3 g of a clathrate decomposition product. Evening primrose seed oil contains about 8% of the physiologically active substance γ-linolenic acid (C _18-3 ), but a large amount of linoleic acid (C _18-2 ), which has one less double bond. Because of this, its concentration becomes extremely complicated using the usual urea addition method. However, according to this example, as shown in Table 5, the γ-linolenic acid in the total effluent was concentrated to about twice the average composition in one simple operation, and the γ-linolenic acid in the clathrate formed , the raw material composition ratio has decreased to about one-third. On the other hand, since linoleic acid is contained in the clathrate decomposition product at a considerable concentration, it is possible to concentrate γ-linolenic acid with high purity by repeating this operation.

【table】

[Table] Example 5 A fatty acid mixture having the composition shown in Table 6 was prepared and separated in the same manner as in Example 1. Using carbon dioxide as supercritical gas, temperature 40℃, pressure 150Kg/cm ² G
I did it. As the inclusion lattice component, 95.3 g of urea pulverized with a vibrating ball mill was used. Changes in the effluent composition of saturated fatty acids and _C18 fatty acids are shown in Table 6 and FIGS. 7 and 8. Regarding these, an attempt was made to compare the separation performance with the supercritical gas extraction method, and it was found that the present example was superior. That is, in this example, during inclusion formation, the composition of each saturated fatty acid in the effluent was approximately 2% or less, indicating that the separation was extremely good. In addition, in the supercritical gas extraction method,
Although it is extremely difficult to separate components with the same number of carbon atoms, in the present invention, great separation performance can be obtained even by differences in double bonds. Although 5.8 g of the raw fatty acids formed clathrate compounds, they were subjected to decomposition according to the temperature and pressure increase patterns shown in Table 7 and FIG. Here, the degree of pressure increase is
It was determined that supercritical carbon dioxide has sufficient dissolving power for fatty acids even at a final temperature of 90°C. Table 8 and FIG. 10 show changes in the composition of saturated fatty acids flowing out, and it can be seen that fatty acids flow out in descending order of carbon number. Table 9 and Figure 1
1. Figure 12 shows the difference in the change in effluent composition due to the difference in the double bonds of C ₁₈ and C ₂₂ fatty acids, respectively. From these results, it can be seen that the difference in double bonds clearly appears when the clathrate compound is decomposed, and the greater the degree of unsaturation, the easier it is to decompose.

【table】

【table】

【table】

【table】

【table】

[Table] Example 6 1.02 g of methanol, which is a good solvent for urea, was added in advance as an entrainer to 5.02 g of fatty acid methyl ester obtained from fish oil with the same composition as that used in Example 1, and the inclusion lattice components were Using 102.2g of pulverized urea, 100kg/nitrous oxide was added at 20℃
Separation was carried out in a high-pressure liquefied gas state of cm ² G in the presence of methanol as a solvent. The temperature and pressure increase patterns are shown in Table 10 and Figure 13, and the results are shown in Table 11, Table 12, Figures 14 and 15.
As shown in Figure 2, the formation of clathrate compounds is clearly observed, unlike in the case where methanol is not added, which will be described later, and it is clear that methanol has the ability to activate the formation of urea adducts even in supercritical or high-pressure liquefied gas. For comparison, nitrous oxide was heated at 20℃ and 100Kg/cm ² G.
We used the same fatty acid methyl ester raw material as in this example as a solvent in the high-pressure liquefied gas state of was consistent with the raw material composition within the analytical error range, regardless of the extraction rate. Furthermore, using urea as an inclusion lattice component did not change the results. In other words, no clathrate formation occurred. Therefore, it is understood that not only the selection of the inclusion lattice component but also the type of gas and the selection of the entrainer are important factors as conditions necessary for the formation of an clathrate compound.

【table】

【table】

【table】

[Table] Example 7 Using the separation apparatus shown in Figure 2, 70 g of deoxycholic acid was charged into the clathrate formation tank 6 for 4.5 g of fatty acid methyl ester obtained from fish oil, and nitrous oxide was used as a solvent. I conducted a separation experiment. pressure
When carried out at 100Kg/cm ² G and a temperature of 20°C, 2.6g of effluent, which is 58% of the raw material, was obtained. Then, as shown in Table 13 and Figure 16, the pressure
Kg/cm ² G and gradually raised the temperature to 90℃, 1.2g of clathrate decomposition products were obtained, and the overall effluent rate was 84%.
It became. The results are shown in Tables 14 and 15, as well as FIGS. 17 and 18. In this case, unlike in Example 6, the clathrate was formed without the need for an entrainer, but deoxycholic acid is not as selective for clathrate formation as urea in separating fatty acid methyl esters. I understand that.

【table】

【table】

[Table] "Effects of the invention" An extraction phase is obtained from a mixture using supercritical gas or high-pressure liquefied gas as a solvent, and using this extraction phase as a medium, the inclusion lattice component and the solute component in the extraction phase are allowed to react, thereby selectively When clathrate compounds are reversibly formed and decomposed, the low viscosity and high permeability of supercritical gas or high-pressure liquefied gas have an advantageous effect on clathrate compounds, which are heterophasic reactions. It is now possible to separate a desired target component with high purity and high yield even from components with very similar structures, which was considered extremely difficult with conventional and supercritical gas extraction methods. In addition, if the supercritical gas or high-pressure liquefied gas used as a solvent has a low degree of activation of the formation of clathrate compounds, if an entrainer that has the ability to activate clathrate formation is coexisting with the supercritical gas or high-pressure liquefied gas, the clathrate formation can be activated. It was found that it promotes the activation of the formation of. As a result, the inclusion separation method of the present invention can be applied to all mixtures to be separated in which a supercritical gas or high-pressure liquefied gas and an inclusion lattice component are found. Furthermore, an extraction phase is obtained from the mixture using supercritical gas or high-pressure liquefied gas as a solvent, and using this extraction phase as a medium, the inclusion lattice component and the solute component in the extraction phase are reacted in the supercritical gas or high-pressure liquefied gas phase. In this case, the equilibrium reaction of the clathrate follows the temperature extremely sensitively, and by increasing the temperature, the equilibrium can be shifted from the direction of clathrate formation to decomposition in a relatively short time, and by selecting an appropriate pressure, The solvent capacity can be sufficiently maintained in the temperature range from clathration formation to decomposition. Furthermore, separation of solute and solvent, which is a characteristic of supercritical fluids, becomes extremely easy. Thus, it has been found that using temperature and pressure as operating factors in a supercritical gas or high-pressure liquefied gas phase can significantly change the solvent capacity in terms of both solubility and ease of inclusion reaction. , the present invention can significantly change the solvent capacity simply by operating temperature and pressure as control factors, thereby making it possible to separate a given target component with high purity and high yield, and improving the fractionation process. I made it possible to simplify it. Furthermore, since the solvent for supercritical fluid extraction and clathrate formation reaction is the same, just by adjusting the temperature and pressure in the system as appropriate, the extraction of the desired solute component and the formation and decomposition of the clathrate compound can be achieved. It is a separation method that is highly compatible with the process, as it can perform the separation from the solvent continuously, and can recycle and reuse the lattice components and supercritical gas or high-pressure liquefied gas. As described above, the inclusion separation method of the present invention has excellent industrial applicability, such as being applicable to a wide range of mixed substances to be separated, simplifying the separation process, and being highly compatible with the process. However, this feature is particularly useful for objects that cannot be separated at high temperatures, such as foods and pharmaceuticals, as they can be operated near room temperature, and for the separation of azeotropic mixtures. Examples include those that require a large amount of energy and complicated operations, such as
Further, the present invention is expected to be applied to the field of analytical chemistry as supercritical chromatography.

[Brief explanation of drawings]

Fig. 1 is a conceptual diagram of the continuous separation process according to the method of the present invention, Fig. 2 is a conceptual diagram of the semi-batch type separator used in the examples, and Fig. 3 is a conceptual diagram of the C ₂₀ due to the difference in the number of double bonds in the effluent. Figure 4 is a graph showing the composition of fatty acid methyl ester of C22 due to the difference in the number of double bonds in the effluent. Figure 5 is a graph showing the composition of C ₂₂ fatty acid methyl ester depending on the number of double bonds in the effluent. A graph showing the composition of _C18 fatty acid ethyl ester due to the difference in number. Figure 6 is a graph showing the change in the composition of the effluent of fatty acid methyl ester as a main component obtained from fish oil. Figure 7 is a graph showing the composition of saturated fatty acids. Figure 8 is a graph showing the composition of the effluent during inclusion formation.
A graph showing the composition of the effluent during clathrate formation of _C18 fatty acids, Fig. 9 is a graph showing the temperature and pressure increase pattern, and Fig. 10 shows the composition of the effluent during the decomposition of clathrate compounds of saturated fatty acids. 11 is a graph showing the outflow composition during the decomposition of clathrate compounds of C ₁₈ fatty acids, FIG. 12 is a graph showing the outflow composition during the decomposition of clathrate compounds of C ₂₂ fatty acids, and 13 The figure is a graph showing temperature and pressure increase patterns, Figure 14 is a graph showing effluent composition during inclusion formation and decomposition of saturated fatty acids and unsaturated fatty acid methyl esters having one double bond, and Figure 15 is a graph showing the clathrate compound of highly unsaturated fatty acid methyl ester having two or more double bonds and the composition of the effluent during decomposition, Figure 16 is a graph showing the temperature increase and pressure increase pattern, and Figure 17 is the saturated and FIG. 18 is a graph showing the effluent composition of fatty acid methyl ester having one double bond, and FIG. 18 is a graph showing the effluent composition of highly unsaturated fatty acid methyl ester having two or more double bonds.

Claims (1)

[Claims] 1. An extraction phase is obtained from a mixture using supercritical gas or high-pressure liquefied gas as a solvent, and this extraction phase is used as a medium. If the solvent gas has a low degree of activation of the formation of clathrate compounds, In this, an entrainer having the ability to activate inclusion formation is coexisting, pressure and temperature are used as operating factors, and the inclusion lattice component and the solute component in the extraction phase are reacted to selectively and reversibly form the clathrate compound. Inclusion using supercritical gas or high-pressure liquefied gas as a medium. Separation method. 2. The clathrate separation method using supercritical gas or high-pressure liquefied gas as a medium according to claim 1, wherein the solvent is carbon dioxide or nitrous oxide. 3. An inclusion separation method using supercritical gas or high-pressure liquefied gas as a medium according to claim 1, wherein the inclusion lattice component is urea or deoxycholic acid. 4. The clathrate separation method using supercritical gas or high-pressure liquefied gas as a medium according to claim 1, wherein the mixture component is a fatty acid or a fatty acid ester. 5. The inclusion separation method using supercritical gas or high-pressure liquefied gas as a medium according to claim 1, wherein the entrainer is methanol when the solvent is nitrous oxide and the inclusion lattice component is urea.