JP5753337B2 - Method for producing finely divided potassium ferricyanide - Google Patents

Description

  The present invention relates to finely divided potassium ferricyanide used as an electron acceptor contained in a reaction part of a biosensor, and a method for producing the same.

  Conventionally, a biosensor for measuring a blood glucose level and the like of a specimen and a manufacturing method thereof have been devised (see, for example, Patent Document 1). In the case of the production method described in Patent Document 1, the reaction part of the biosensor is formed by applying a reaction part coating solution containing an oxidoreductase, an electron acceptor and the like on the working electrode and the counter electrode and drying it. The As the electron acceptor, finely divided potassium ferricyanide is used.

Conventionally, this fine-grained potassium ferricyanide is prepared by dissolving potassium ferricyanide in distilled water to prepare an aqueous potassium ferricyanide solution, and dropping the aqueous solution into ethanol to precipitate potassium ferricyanide, followed by centrifugation and washing with ethanol. And was freeze-dried. However, this manufacturing method is cumbersome and not efficient. It is also necessary to reduce the particle size of the finely divided potassium ferricyanide. Accordingly, a method for producing finely divided potassium ferricyanide has been devised that can produce finely divided potassium ferricyanide efficiently and can make the particle diameter smaller so that the reaction is stabilized (for example, see Patent Document 2). However, it is desired to further reduce the particle size of finely divided potassium ferricyanide.

International Publication No. 2004/017057 Pamphlet JP 2007-269547 A

  Therefore, the inventor of the present invention has come to the present invention as a result of intensive studies to investigate the cause of such a problem and solve such a problem.

  That is, an object of the present invention is to provide a method for producing finely divided potassium ferricyanide capable of further reducing the particle diameter.

Method for producing a grain refining potassium ferricyanide present invention, with flow hydrophilic organic solvent at a constant flow rate in the closed path, potassium ferricyanide aqueous solution, at a constant flow rate into the enclosed path, hydrophilic flowing said seal closed path Flowing near the center of the organic solvent and mixing the hydrophilic organic solvent and the aqueous potassium ferricyanide solution with air in a non-contact state to form a suspension.

Further, the method for producing finely divided potassium ferricyanide according to the present invention is the method for producing finely divided potassium ferricyanide , wherein the aqueous solution of potassium ferricyanide flows through the sealed path at a constant flow rate into the sealed path. In the vicinity of the center of the solvent, the hydrophilic organic solvent flows in the flow direction .

The method for producing finely divided potassium ferricyanide according to the present invention is characterized in that, in the method for producing finely divided potassium ferricyanide, the constant flow rate of the hydrophilic organic solvent is larger than the constant flow rate of the aqueous potassium ferricyanide solution. To do.

The method for producing finely divided potassium ferricyanide according to the present invention is the method for producing finely divided potassium ferricyanide, wherein the sealed route is continuous with the first route for supplying the hydrophilic organic solvent and the first route. It comprises a second path, and the aqueous potassium ferricyanide solution is allowed to flow into the second path at a constant flow rate to mix the hydrophilic organic solvent and the aqueous potassium ferricyanide solution with air in a non-contact state.

  According to the method for producing finely divided potassium ferricyanide according to the present invention, a suspension is prepared by mixing an aqueous solution of potassium ferricyanide and a hydrophilic organic solvent in a non-contact state with air, so that the median diameter of particles (50 It was possible to produce finely divided potassium ferricyanide having a smaller% diameter) than before.

  Next, the method for producing finely divided potassium ferricyanide according to the present invention and the finely divided potassium ferricyanide produced by the production method will be described in detail based on the drawings.

  The method for producing finely divided potassium ferricyanide according to the present invention comprises a step of preparing a potassium ferricyanide solution, a step of preparing a suspension, a step of concentrating the suspension by centrifugation, and a concentrated suspension. And a step of drying. Note that this suspension may be used after being washed and replaced with a hydrophilic organic solvent without drying to make a paste or slurry.

The step of preparing the aqueous potassium ferricyanide solution is a step of preparing the aqueous potassium ferricyanide solution 10 by dissolving potassium ferricyanide in water. The concentration of potassium ferricyanide in the aqueous potassium ferricyanide solution 10 is desirably higher in order to increase production efficiency.

As shown in FIG. 1, the step of preparing the suspension is performed by causing the hydrophilic organic solvent A to flow at a constant flow rate in the L-shaped sealed path 10, and for the potassium ferricyanide aqueous solution B to be in the vicinity of the L-shaped bend. In this step, a suspension C is produced by flowing a constant flow rate from the needle 12 into the sealed path 10 and mixing the hydrophilic organic solvent A and the aqueous potassium ferricyanide solution B in a non-contact state with air. The sealed path 10 is composed of a first path 14 for supplying the hydrophilic organic solvent A and a second path 16 continuous in a direction perpendicular to the first path 14, and the potassium ferricyanide aqueous solution B is passed from the needle 12 to the first path 14. The hydrophilic organic solvent A and the potassium ferricyanide aqueous solution B can be mixed in a non-contact state with air by flowing into the second path 16 at a constant flow rate. Since the potassium ferricyanide aqueous solution B flows out from the needle 12 in the ethanol flow direction in the vicinity of the center of the ethanol A flowing through the sealed path 10, it is mixed evenly. In the present specification and claims, the hydrophilic organic solvent is a non-solvent or poor solvent for potassium ferricyanide and miscible with water. For example, methanol, ethanol, isopropyl alcohol, acetone and the like can be mentioned, and ethanol is particularly preferable.

The needle 12 and the first path 14 are each connected to a liquid feed pump, and by driving the liquid feed pump, the fluid can flow at a constant flow rate. The constant flow rate (ml / S) of ethanol A is 3 to 20 times, particularly preferably 5 to 16 times, the constant flow rate (ml / S) of aqueous potassium ferricyanide solution B. This magnification represents the mixing ratio of ethanol A to potassium ferricyanide aqueous solution B, and if it is too large, the production efficiency is deteriorated.

  The step of centrifuging and suspending the suspension is a step in which the suspension C is taken out from the sealed path 10 and subjected to centrifugal separation and washing with ethanol several times. Specifically, after removing unnecessary ethanol in a state where finely divided potassium ferricyanide is separated by a centrifuge, ethanol is added and mixed. This is to remove moisture. The step of drying the concentrated suspension is a step of freeze-drying this finely divided potassium ferricyanide to obtain powdered finely divided potassium ferricyanide. Drying by normal temperature or heating may be used.

  In such a method for producing finely divided potassium ferricyanide, ethanol A is allowed to flow at a constant flow rate in the first path 14, and the aqueous potassium ferricyanide solution B is allowed to flow from the needle 12 to the first path 14 at a constant flow rate. Efficient mixing can be performed at a mixing ratio. Moreover, since the flow volume of ethanol and potassium ferricyanide aqueous solution can be controlled with a liquid feeding pump, the flow volume ratio can be objectively grasped as a mixing ratio.

  As mentioned above, although one Embodiment of this invention was described, this invention can be implemented also in another aspect. For example, the sealed path 10 is not limited to an L shape, and may have a square shape as shown in FIG. Moreover, the linear shape as shown in FIG. 3 may be sufficient. In these cases, it is considered that ethanol A can flow more smoothly.

  In addition, the technical scope of the present invention includes embodiments in which various improvements, modifications, and variations are added based on the knowledge of those skilled in the art without departing from the spirit of the present invention. Moreover, you may implement with the form which substituted any invention specific matter to the other technique within the range which the same effect | action or effect produces.

  In the following manner, finely divided potassium ferricyanide was actually produced by the production method of the present invention, and the particle diameter was measured.

Example 1
Potassium ferricyanide was dissolved in distilled water to prepare a 25 wt% potassium ferricyanide aqueous solution. This potassium ferricyanide aqueous solution was supplied from a 0.41 φmm needle at a flow rate of 0.83 ml / s and 95.4 vol% ethanol solution at a flow rate of 5.0 ml / s with a feed pump. An ethanol suspension of potassium ferricyanide was obtained. The temperature of both solutions before mixing was kept at 40 ° C. Thereafter, centrifugation (maximum 10,000 G) at 4 ° C. for 5 minutes and washing with 99.94 vol% ethanol were performed three times, followed by vacuum drying to obtain a powder product of finely divided potassium ferricyanide.

(Example 2)
Potassium ferricyanide was dissolved in distilled water to prepare a 25 wt% potassium ferricyanide aqueous solution. This potassium ferricyanide aqueous solution was supplied from a 0.41 φmm needle at a flow rate of 0.83 ml / s and 95.4 vol% ethanol solution at a flow rate of 8.3 ml / s, respectively, and these were combined and mixed by contact method B, and reprecipitated. An ethanol suspension of potassium ferricyanide was obtained. The temperature of both solutions before mixing was kept at 40 ° C. Thereafter, centrifugation (maximum 10,000 G) at 4 ° C. for 5 minutes and washing with 99.94 vol% ethanol were performed three times, followed by vacuum drying to obtain a powder product of finely divided potassium ferricyanide.

(Example 3)
Potassium ferricyanide was dissolved in distilled water to prepare a 25 wt% potassium ferricyanide aqueous solution. This aqueous solution of potassium ferricyanide was supplied from a 0.19 φmm needle at a flow rate of 0.26 ml / s and 95.4 vol% ethanol solution at a flow rate of 2.6 ml / s with a feed pump. An ethanol suspension of potassium ferricyanide was obtained. The temperature of both solutions before mixing was kept at 40 ° C. Thereafter, centrifugation (maximum 10,000 G) at 4 ° C. for 5 minutes and washing with 99.94 vol% ethanol were performed three times, followed by vacuum drying to obtain a powder product of finely divided potassium ferricyanide.

Example 4
Potassium ferricyanide was dissolved in distilled water to prepare a 25 wt% potassium ferricyanide aqueous solution. This potassium ferricyanide aqueous solution was supplied from a 0.41 φmm needle with 0.83 ml / s and 99.94 vol% ethanol solution at a flow rate of 5.0 ml / s with a liquid feed pump, and these were combined and mixed by contact method B and reprecipitated. An ethanol suspension of potassium ferricyanide was obtained. The temperature of both solutions before mixing was kept at 40 ° C. Thereafter, centrifugation (maximum 10,000 G) at 4 ° C. for 5 minutes and washing with 99.94 vol% ethanol were performed three times, followed by vacuum drying to obtain a powder product of finely divided potassium ferricyanide.

(Example 5)
Potassium ferricyanide was dissolved in distilled water to prepare a 25 wt% potassium ferricyanide aqueous solution. This potassium ferricyanide aqueous solution was supplied from a 0.41 φmm needle at a flow rate of 0.83 ml / s and 95.4 vol% ethanol solution at a flow rate of 5.0 ml / s with a feed pump. An ethanol suspension of potassium ferricyanide was obtained. The temperature of both solutions before mixing was kept at 0 ° C. Thereafter, centrifugation (maximum 10,000 G) at 4 ° C. for 5 minutes and washing with 99.94 vol% ethanol were performed three times, followed by vacuum drying to obtain a powder product of finely divided potassium ferricyanide.

(Comparative Example 1)
Potassium ferricyanide was dissolved in distilled water to prepare a 25 wt% potassium ferricyanide aqueous solution. This potassium ferricyanide aqueous solution was supplied from a 0.41 φmm needle at a flow rate of 0.83 ml / s and 95.4 vol% ethanol solution at a flow rate of 5.0 ml / s with a liquid feed pump, and these were combined and mixed by contact method A and reprecipitated. An ethanol suspension of potassium ferricyanide was obtained. The temperature of both solutions before mixing was kept at 40 ° C. Thereafter, centrifugation (maximum 10,000 G) at 4 ° C. for 5 minutes and washing with 99.94 vol% ethanol were performed three times, followed by vacuum drying to obtain a powder product of finely divided potassium ferricyanide.

(Comparative Example 2)
Potassium ferricyanide was dissolved in distilled water to prepare a 25 wt% potassium ferricyanide aqueous solution. This potassium ferricyanide aqueous solution was supplied from a 0.41 φmm needle at a flow rate of 0.83 ml / s and 95.4 vol% ethanol solution at a flow rate of 8.3 ml / s, respectively, and these were combined and mixed by contact method A and reprecipitated. An ethanol suspension of potassium ferricyanide was obtained. The temperature of both solutions before mixing was kept at 40 ° C. Thereafter, centrifugation (maximum 10,000 G) at 4 ° C. for 5 minutes and washing with 99.94 vol% ethanol were performed three times, followed by vacuum drying to obtain a powder product of finely divided potassium ferricyanide.

(Comparative Example 3)
Potassium ferricyanide was dissolved in distilled water to prepare a 25 wt% potassium ferricyanide aqueous solution. This aqueous solution of potassium ferricyanide was supplied from a 0.19 φmm needle at a flow rate of 0.26 ml / s and 95.4 vol% ethanol solution at a flow rate of 2.6 ml / s, respectively. An ethanol suspension of potassium ferricyanide was obtained. The temperature of both solutions before mixing was kept at 40 ° C. Thereafter, centrifugation (maximum 10,000 G) at 4 ° C. for 5 minutes and washing with 99.94 vol% ethanol were performed three times, followed by vacuum drying to obtain a powder product of finely divided potassium ferricyanide.

(Comparative Example 4)
Potassium ferricyanide was dissolved in distilled water to prepare a 25 wt% potassium ferricyanide aqueous solution. This potassium ferricyanide aqueous solution was supplied from a 0.41 φmm needle with 0.83 ml / s and 99.94 vol% ethanol solution at a flow rate of 5.0 ml / s with a liquid feed pump, and these were combined and mixed by contact method A and reprecipitated. An ethanol suspension of potassium ferricyanide was obtained. The temperature of both solutions before mixing was kept at 40 ° C. Thereafter, centrifugation (maximum 10,000 G) at 4 ° C. for 5 minutes and washing with 99.94 vol% ethanol were performed three times, followed by vacuum drying to obtain a powder product of finely divided potassium ferricyanide.

(Comparative Example 5)
Potassium ferricyanide was dissolved in distilled water to prepare a 25 wt% potassium ferricyanide aqueous solution. This potassium ferricyanide aqueous solution was supplied from a 0.41 φmm needle at a flow rate of 0.83 ml / s and 95.4 vol% ethanol solution at a flow rate of 5.0 ml / s with a liquid feed pump, and these were combined and mixed by contact method A and reprecipitated. An ethanol suspension of potassium ferricyanide was obtained. The temperature of both solutions before mixing was kept at 0 ° C.

(Evaluation method)
Tables 1 and 2 show the results of measuring the particle size of the obtained finely divided potassium ferricyanide using a laser diffraction particle size distribution analyzer SALD-200VER manufactured by Shimadzu Corporation. In Tables 1 and 2, the contact method “B” is the method shown in FIG. 1 in a non-contact state with air, and the contact method “A” is the method shown in FIG. 4 in a contact state with air. is there. “Ferri” is potassium ferricyanide.

About Examples 1-5, as shown in Table 1, the average value of the median diameter (50% diameter) was 1.7 μm. On the other hand, as shown in Table 2 for Comparative Examples 1 to 5, the median diameter average value was 2.7 μm. Thus, it was found that the finely divided potassium ferricyanide produced by the production method of the present invention has a smaller median diameter than the finely divided potassium ferricyanide produced by the production method of the comparative example.

Further, as shown in FIG. 5 (a), even when the ethanol purity is changed, the fine-grained potassium ferricyanide produced by the production method of the present invention is more effective than the fine-grained potassium ferricyanide produced by the production method of the comparative example. However, as shown in FIG. 5B, the finely divided potassium ferricyanide produced by the production method of the present invention is smaller than that produced by the production method of the comparative example as shown in FIG. The median diameter is smaller than that of granulated potassium ferricyanide, and as shown in FIG. 5 (c), even when the atomization temperature is changed, finely divided potassium ferricyanide produced by the production method of the present invention is a comparative example. Even if the median diameter is smaller than that of finely divided potassium ferricyanide produced by the production method and the atomization temperature is changed as shown in FIG. Towards the grain refining potassium ferricyanide produced by the production method, than comminuted potassium ferricyanide produced by the production method of the comparative example, it median diameter smaller was found. Furthermore, even if the finely divided potassium ferricyanide produced by the production method of the present invention and the finely divided potassium ferricyanide produced by the production method of the comparative example are visually compared in FIG. It is clear that the finely divided potassium ferricyanide produced by the production method has a smaller median diameter than the finely divided potassium ferricyanide produced by the production method of the comparative example. 5 and 6, “close” indicates the case of the present invention, and “open” indicates the case of the comparative example.

If finely divided potassium ferricyanide composed of fine median diameter particles can be obtained, for example, when finely divided potassium ferricyanide is used as an electron acceptor for producing a biosensor, Sedimentation is difficult to occur.

  According to the method for producing finely divided potassium ferricyanide of the present invention, finely divided potassium ferricyanide having smaller particles can be produced. For this reason, it can be widely used for the production of fine-grained potassium ferricyanide used as a raw material for various products.

It is a top view for demonstrating the mixing step in the manufacturing method of the fine grain ferricyanide of this invention. It is a top view for demonstrating other embodiment of the mixing step in the manufacturing method of the fine grain potassium ferricyanide of this invention. It is a top view for demonstrating other embodiment of the mixing step in the manufacturing method of the fine grain potassium ferricyanide of this invention. It is a top view for demonstrating the mixing step in the manufacturing method of the conventional fine grain potassium ferricyanide. It is a graph which shows the effect of the manufacturing method of the fine grain potassium ferricyanide of this invention, The figure (a) is a graph which compared the median diameter for every ethanol purity, The figure (b) is the median diameter for every needle diameter. (C) is a graph comparing the median diameter for each atomization temperature, and (d) is a graph comparing the median diameter for each flow rate ratio. It is a photograph which shows the effect of the manufacturing method of the fine grain potassium ferricyanide of this invention.

Explanation of symbols

A: Ethanol B: Potassium ferricyanide aqueous solution C: Suspension 10: Sealing path 12: Needle 14: First path 16: Second path

Claims (4)

A hydrophilic organic solvent is allowed to flow at a constant flow rate in the sealed path , and an aqueous potassium ferricyanide solution is allowed to flow into the sealed path at a constant flow rate in the vicinity of the center of the hydrophilic organic solvent flowing through the sealed path. A step of mixing a solvent and the aqueous potassium ferricyanide solution with air in a non-contact state to produce a suspension, and a method for producing fine-grained potassium ferricyanide. 2. The finely divided ferritic ferric acid solution according to claim 1, wherein the aqueous potassium ferricyanide solution is allowed to flow in the flow direction of the hydrophilic organic solvent in the vicinity of the center of the hydrophilic organic solvent flowing through the sealed path at a constant flow rate into the sealed path. A method for producing potassium cyanide.   The method for producing fine-grained potassium ferricyanide according to claim 2, wherein the constant flow rate of the hydrophilic organic solvent is larger than the constant flow rate of the aqueous potassium ferricyanide solution. The sealed path is composed of a first path for supplying a hydrophilic organic solvent and a second path continuous to the first path, and an aqueous potassium ferricyanide solution is allowed to flow into the second path at a constant flow rate, The method for producing finely divided potassium ferricyanide according to any one of claims 1 to 3, wherein the hydrophilic organic solvent and the aqueous potassium ferricyanide solution are mixed in a non-contact state with air.

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