JP3138466B2 - Method for producing spherical microgels composed of polysaccharides - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a method for producing a spherical microgel comprising a polysaccharide. The spherical microgel comprising the polysaccharide produced by the method of the present invention can be used in the fields of confectionery, cosmetics, pharmaceuticals and the like.

[Problems to be solved by conventional technology and invention]

As is well known, polysaccharide gels are widely used in the fields of confectionery, cosmetics, pharmaceuticals, and the like, and the methods for producing the gels and their uses are various. However, it is extremely difficult to produce a spherical microgel having an arbitrary particle size of several μm to several hundred μm, and the conventional microgel production involves forming a gel and then pulverizing it by external force to miniaturize it. And the surface of the obtained microgel was not necessarily smooth.

Further, there is no conventional technology that adopts the concept of producing a microgel having a particle size by aging coacervate in producing a microgel.

On the other hand, as pharmaceuticals, gels have been developed as drug delivery systems. The microcapsule component at that time is a polymer electrolyte such as gelatin,
Since the shape is formed by adding an organic solvent or adjusting the pH, etc., safe microencapsulation cannot always be performed while maintaining a gentle environment.

Japanese Patent Application Laid-Open No. 63-287544 discloses a method for producing microcapsules by phase separation by dehydration using a nontoxic substance as a wall substance and a dehydrating substance. However, in the present invention, the particle diameter of the microcapsules is not arbitrarily controlled, and the inside of the microcapsules is not a uniform gel.

Further, as a microcapsule having a particle diameter of 1 mm or less, an application using an aggregate (liposome) of phospholipids is known, but the components are expensive and the stability is insufficient.

Furthermore, although there is a method of making microcapsules having a particle size of 1 mm or less composed of multiple components, for example, microcapsules using gelatin or a cellulose derivative,
Techniques for producing microcapsules and spherical microgels composed of only polysaccharides having a milder action on the living body have not yet been known.

In view of the current situation as described above, development of materials that can be easily used in foods, cosmetics, and medicines, that is, microcapsules having an expected particle size due to a polysaccharide having a very mild action on the living body and a phase separation accelerator. Is expected.

[Means and actions for solving the problem]

The present invention relates to a method for producing a spherical microgel comprising a polysaccharide. That is, the present invention provides a spherical microgel by mixing and stirring a polysaccharide aqueous solution and a phase separation accelerator aqueous solution in a heated state to prepare a coacervate suspension, and rapidly cooling the coacervate suspension from the heated state to gel. A method for producing a spherical microgel comprising a polysaccharide, characterized in that the coacervate aqueous solution is mixed with an aqueous solution of a phase separation accelerator in a heated state, and the coacervate suspension is rapidly cooled from the heated state. In producing the spherical microgel, a ripening time is set from the time of the adjustment to the time of the quenching, and a polysaccharide characterized by controlling the particle size of the spherical microgel to be generated by adjusting the aging time. The present invention relates to a method for producing a spherical microgel.

 Hereinafter, the present invention will be described in detail.

In order to produce a spherical microgel according to the present invention, first, a polysaccharide aqueous solution and a phase separation accelerator aqueous solution are mixed to prepare a coacervate suspension. Here, conditions necessary for producing a spherical microgel are described. Were examined in various ways. As a result, an intended spherical microgel could be obtained by performing the following operations.

That is, both the aqueous solution of the polysaccharide and the aqueous solution of the phase separation accelerator are mixed in a heated state and rapidly stirred to prepare a coacervate suspension. Thereafter, in order to obtain a coacervate having an intended particle size, the coacervate is allowed to stand still and aged for 0 to 40 minutes to induce its fusion. Since the particle size of the spherical microgel becomes larger due to coalescence of the coacervate with the elapse of the aging time, after a predetermined time elapses, it is rapidly cooled from a heated state to gel to form a coacervate gel, in other words, a spherical microgel.

The inner phase of the spherical microgel obtained here is prepared by quenching treatment, and therefore has a substantially uniform density, and is not a microcapsule having a so-called outer wall having a high outer wall portion of the sphere.

On the other hand, since the spherical microgel is in a state of being suspended in the aqueous solution of the phase separation accelerator, it varies depending on the particle size, but it is subjected to centrifugal separation at approximately 3,000 rpm for 10 minutes to remove the supernatant, thereby obtaining the phase separation accelerator. To separate. By repeating washing with distilled water and centrifugal separation of the precipitated spherical microgel, a spherical microgel containing only a polysaccharide without a phase separation accelerator can be obtained.

The coacervate suspension may be in a heated state before cooling to such an extent that the polysaccharide used is gelled by cooling.

Since the fusion of coacervate is promoted by the heat treatment, the polysaccharide aqueous solution and the phase separation accelerator aqueous solution are heated to a predetermined temperature required for gelation in advance, mixed and stirred to prepare coacervate, and then statically heated at the same temperature. It is better to place and ripen, and then to gel by cooling.
This is because if the coacervate is heated after preparation, the coacervate fusion proceeds excessively until the temperature reaches a predetermined temperature, and it may be difficult to obtain a spherical microgel having an intended particle size.
However, when strict particle size control is not required, it is also possible to mix the aqueous solution of the polysaccharide and the aqueous solution of the phase separation accelerator before heating.

In any case, when the heat treatment temperature is around 100 ° C. or higher, the boiling point of the aqueous solution of polysaccharide is close to that, and the formation of the gel becomes unstable. Therefore, it is difficult to control the formation of a spherical microgel having a uniform particle size. From such a viewpoint, the heat treatment temperature of the coacervate suspension is preferably from 80 to 95 ° C.

In the course of the above operation, the aging time for controlling the particle size varies depending on the polysaccharide used, but is preferably within about 40 minutes. If the aging time exceeds 40 minutes, the coalescence of the coacervate proceeds more than expected, and the particle size of the fused coacervate becomes excessively large, making it difficult to maintain its shape.

The polysaccharide used in the present invention produces coacervate by stirring with a phase separation accelerator, and
Any substance may be used as long as it forms a coacervate gel by heating and quenching, and examples thereof include one or a mixture of two or more kinds of starch, pullulan, agar, carrageenan and the like.

The phase separation accelerator is a polymer compound that is water-soluble and does not actively interact with the polysaccharide,
Any substance that can be mixed with a polysaccharide to cause phase separation as a coacervate, and that is nontoxic to living organisms from the intended use of the spherical microgel of the present invention, or that can be detoxified by washing and removing. And polyethylene oxide (hereinafter, referred to as PEO), polyvinylpyrrolidone (hereinafter, referred to as PVP).
Alternatively, polyvinyl alcohol (hereinafter, referred to as PVA)
And the like, or a mixture of two or more.

 Next, a further description will be given using experimental examples.

Experimental Example 1. In this experiment, starch was used as a polysaccharide and PEO was used as a phase separation accelerator.

That is, to sufficiently dissolve the starch, 500 ml of a 21.6% starch aqueous solution heated to 85 ° C. and 500 ml of a 17.6% PEO aqueous solution heated to 85 ° C. by mixing the temperature of the starch aqueous solution were mixed, and rapidly rotated at 1000 rpm. Stirring was performed to prepare a coacervate suspension. 100 ml of the mixed solution containing the coacervate was dispensed at a time, and nine samples were prepared so that the aging time could be observed from 0 minutes to 4 minutes at intervals of 32 minutes.
Next, each sample was allowed to stand at a temperature of 85 ° C. for a predetermined period of time to ripen, to induce coacervate fusion, and then immediately cooled to 1 ° C. to form a gel, thereby forming spherical microgels having nine different average particle diameters. Obtained.

In this experiment, during the preparation and aging of the coacervate, the starch aqueous solution and the PEO aqueous solution were each already heated to 85 ° C before mixing, and the coacervate suspension that was the mixed solution was also kept at 85 ° C. Because
No heating was performed again.

Table 1 shows the results of measuring the average particle size of the spherical microgel obtained in this experiment using an optical microscope.

As is clear from Table 1, in this experiment, a spherical microgel having an average particle size of 28 to 587 μm was obtained depending on the aging time after the formation of the coacervate. That is, this experiment revealed that a spherical microgel having a required particle size can be prepared by specifying the aging time and rapidly cooling.

 Table 1 Sample No. Leaving time (minutes) Average particle size (μm) An example will be described.

Example 1. After heating 20 ml of a 21.6% pullulan aqueous solution and 200 ml of a 17.6% PEO aqueous solution to 88 ° C., both were mixed and rapidly stirred at 800 rpm to produce a coacervate turbid liquid. This coacervate dispersion was divided into two parts, one was immediately cooled to 2 ° C. immediately, and the other was allowed to stand for 5 minutes to mature and then rapidly cooled to form spherical microgels.
The average particle size of each of the obtained spherical microgels was 8 μm and 28 μm.

FIG. 1 shows a scanning electron micrograph (the white line on the lower right side represents 10 μm) of the spherical microgel having a particle size of 9 μm in this example. In the course of the electron micrographing operation, the sample was placed in a high vacuum state, but it was confirmed that the sample had a spherical structure as shown in this photograph. Therefore,
It can be seen that the contents of the spheres are filled with gel and are not merely spheres formed by wall formation.

Example 2. A 1.8% agar aqueous suspension was heated to 92 ° C to prepare an agar aqueous solution, and 400 ml of this was prepared. On the other hand, 25% P heated to 92 ° C
Take 100 ml of VP aqueous solution and mix with 400 ml of the agar aqueous solution
The mixture was rapidly stirred at 850 rpm to prepare a coacervate suspension. The coacervate dispersion was divided into two parts, one was immediately cooled to 4 ° C. immediately, and the other was allowed to stand still at 92 ° C. for 8 minutes, aged and then rapidly cooled. As a result, spherical microgels having average particle diameters of 6 μm and 22 μm, respectively, were obtained.

Example 3. 300m of 12.0% carrageenan aqueous solution dissolved in hot water at 65 ° C
l, 200 ml of a 20% PVA aqueous solution at 65 ° C. was mixed and rapidly stirred to prepare a coacervate suspension. Divide this coacervate suspension into two, one without aging
Rapidly heated to 1 ° C. The other was rapidly heated to 85 ° C after 10 minutes of aging and then rapidly cooled to 1 ° C. As a result, spherical microgels having average particle diameters of 19 μm and 72 μm, respectively, were obtained.

〔The invention's effect〕

The spherical microgel produced by the method for producing a spherical microgel of the present invention can be controlled to an arbitrary particle size by controlling its particle size.

According to the method for producing a spherical microgel of the present invention, a non-toxic, harmless spherical microgel can be easily obtained by selecting a polysaccharide and a phase separation accelerator that form the gel. It greatly contributes to the industry.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a scanning electron micrograph showing the particle structure of a spherical microgel obtained by the present invention.

──────────────────────────────────────────────────続 き Continuation of the front page (51) Int.Cl. ⁷ Identification code FI C08L 5:00 (56) References JP-A-2-191540 (JP, A) JP-A-61-263630 (JP, A) JP-A-63-287544 (JP, A) JP-A-57-171432 (JP, A) JP-A-56-74130 (JP, A) JP-A-3-237103 (JP, A) Tamotsu Kondo Modern colloid science 1980 May 30, 2010 Sankyo Publishing Co., Ltd. Pages 107-112 (58) Fields investigated (Int. Cl. ⁷ , DB name) B01J 13/00 A61K 9/16 C08B 37/00

Claims (3)

(57) [Claims] An aqueous solution of a polysaccharide selected from an aqueous starch solution, an aqueous pullulan solution, an agar aqueous solution and a carrageenan aqueous solution and an aqueous solution of a phase separation accelerator selected from an aqueous polyethylene oxide solution, an aqueous polyvinylpyrrolidone solution and an aqueous polyvinyl alcohol solution are mixed and stirred in a heated state. The coacervate suspension is adjusted, and the coacervate suspension is rapidly cooled from a heated state to be gelled to form a spherical microgel. A method for producing a spherical microgel comprising a polysaccharide, wherein the spherical microgel having a particle size corresponding to the standing time is formed by quenching from a heated state after aging by placing the mixture. 2. An aqueous solution of a polysaccharide and an aqueous solution of a phase separation accelerator are mixed after being heated to 80 ° C. to 95 ° C. in advance.
A method for producing a spherical microgel comprising the above polysaccharide. 3. The method for producing a spherical microgel comprising a polysaccharide according to claim 1, wherein the aqueous solution of the polysaccharide and the aqueous solution of the phase separation accelerator are mixed and then heated to 80 ° C. to 95 ° C.