JPWO2007126048A1 - Method for producing uniform and stable suspension and apparatus therefor - Google Patents

Abstract

The present invention provides a simple method for producing a uniform and stable suspension and an apparatus therefor. The present invention also provides a simple method for producing a suspension having a uniform particle size and an apparatus therefor. The present invention relates to a method for uniformly and stably dispersing an object to be processed in a medium by a simple method. More specifically, the present invention relates to a container in which a required amount of a medium and an object to be processed and a “weight” are placed in a container installed in a container holder of a rotation / revolution type defoaming kneading apparatus. A method in which the object to be processed and the medium in the container are kneaded by being rotated and revolved by the rotation and revolution type defoaming kneading apparatus, and the object to be processed and the medium are uniformly dispersed in the medium by being installed in the container holder of the apparatus , A weight therefor, a container having it, and its use.

Description

  The present invention relates to a method for uniformly and stably dispersing an object to be processed on a medium by a simple method. More specifically, the present invention relates to a container in which a required amount of a medium and an object to be processed and a “weight” are placed in a container installed in a container holder of a rotation / revolution type defoaming kneading apparatus. A method in which the object to be processed and the medium in the container are kneaded by being rotated and revolved by the rotation and revolution type defoaming kneading apparatus, and the object to be processed and the medium are uniformly dispersed in the medium by being installed in the container holder of the apparatus , A weight therefor, a container having it, and its use.

Preparation of a suspension in which active ingredients are uniformly and stably suspended is a technology required not only in the field of handling bioactive ingredients such as pharmaceuticals and agricultural chemicals, but also in many industrial fields such as cosmetics and foods. It is. In particular, in the pharmaceutical field, a suspension is used as one of dosage forms, and there is a technique for formulating a uniform and stable suspension from a small scale at an early stage of development to an actual production scale after commercialization. Necessary. Conventionally, the preparation of suspensions has been mainly performed by grinding the active ingredient in a mortar and suspending or kneading the active ingredients in a medium. However, reproducibility such as dispersibility and content uniformity due to handling of the mortar is low, there are quantitative restrictions due to the size of the mortar, and it takes time to grind and knead with the mortar There were many problems.
Furthermore, when suspending the ground particles, if the particles are agglomerated in the medium, and especially when “wetting” with the medium is poor, the particles are separated (floating) at the moment the particles are mixed with the medium. In many cases, uniform dispersion is difficult, and preparation of a uniform and stable suspension has many problems.

As one means for solving these problems, a mixing stirrer that revolves around the inner periphery of a container while rotating a stirring blade is used in order to sufficiently stir solid liquid. For example, a stirrer for kneading food materials (see Patent Document 1), a stirrer having a separate stirring blade for stirring the surface layer above the liquid phase (see Patent Document 2), or dispersion of carbon nanotubes A stirrer (see Patent Document 3) having a special stirrer blade for improving the performance has been proposed.
Furthermore, as an apparatus for kneading the powdery substance and the liquid, the container to be kneaded in the container by the revolving and revolving centrifugal force is further revolved while rotating the container installed inclined with respect to the horizontal axis. Has been developed (see Patent Documents 4 and 5). The container of such an apparatus has a rotation on the rotation shaft and a rotation on the revolution shaft, and kneading with these centrifugal forces, so that the stirring and mixing is compared with the case of using a conventional stirring blade or stirring bar. Not only is it very effective, it can also efficiently degas fine bubbles (see Patent Document 6), and there is no foreign matter such as a stirring blade inside the container in which the components are mixed. There is no problem of adhesion of the material to be kneaded to the stirring blade, and it is not necessary to wash the stirring blade, and has been attracting attention as a simple and effective defoaming kneading apparatus. Such an apparatus is improved by using a fluid as a balancer (see Patent Document 7), in order to knead by centrifugal force by revolution and rotation that is operated at a high speed of several hundred to several thousand revolutions per minute, Improvements have been made to devices (see Patent Document 8) and the like that have taken preventive measures to prevent foreign substances such as lubricating oil from entering the devices. However, in such an apparatus, it is generally difficult to knead substances having greatly different specific gravities, and the rotation speed convenient for stirring the material to be kneaded and the rotation convenient for degassing the material to be kneaded are difficult. It is known that adjustment with speed is difficult. For this purpose, a container provided with a stirring blade (see Patent Document 9), a device capable of adjusting the rotation speed of rotation and revolution (see Patent Document 10), and more uniform kneading. Therefore, improvements such as raising the center of the bottom of the container (see Patent Document 11) have been made.

As described above, an apparatus for rotating and revolving a container installed at an inclination with respect to the horizontal axis and kneading the material to be kneaded in the container by the centrifugal force of rotation and revolution has a strong kneading force and a high removal force. Since it has a foaming action and can be kneaded in a simple and short time, it has been widely used in various industrial fields. For example, a method used for kneading edible powder (see Patent Document 12), a method used for the production of cosmetics and solid cosmetics containing powder (see Patent Documents 13 and 14), suspension for pharmaceutical use The method used to suspend the liquid as it is in the administration liquid bottle (see Patent Document 15), the method used to knead the hyaluronic acid-containing composition of the ophthalmic preparation (see Patent Document 16), etc. In addition, it has been widely used for kneading polymer materials and electrical materials.
However, when trying to knead a substance with poor “wetting” with respect to a liquid medium such as water, the substance agglomerates as soon as it comes into contact with the liquid medium, and the kneaded mass remains kneaded and is uniformly and stably suspended. The liquid cannot be manufactured. Moreover, it was not possible to produce a suspension having a uniform particle size.

JP 2003-135950 A Japanese Patent Laid-Open No. 5-49892 JP 2005-324999 A JP 61-290946 A Japanese Utility Model Publication No. 5-32110 Japanese Patent No. 2711964 JP 2002-85953 A JP 2000-246082 A Japanese Patent No. 3217272 JP 2000-271465 A JP 2001-353405 A JP 2001-299191 A JP 2002-302413 A JP 2006-1883 A JP 2002-320835 A JP-A-2005-154305

  The present invention provides a simple method for producing a dispersion in which an object to be treated such as a uniform and stable suspension is uniformly and stably dispersed in a medium, and an apparatus therefor. The present invention also provides a simple method for producing a dispersion such as a suspension having a uniform particle diameter and an apparatus therefor.

The inventors of the present invention have studied various methods for suspending substances with poor “wetting” in water. Suspension was carried out by conventional methods such as grinding and kneading in a mortar, or a method using a homogenizer with high grinding efficiency, but precipitation occurred after storage for 1 week to produce a stable suspension. I couldn't. Furthermore, while rotating the container holder that is inclined with respect to the horizontal axis and the bottomed cylindrical container that is held substantially coaxially with the container holder, the container holder is further rotated to rotate and rotate and rotate. Using an apparatus for kneading the material to be kneaded by force (hereinafter referred to as a rotation / revolution type defoaming kneading apparatus), an attempt was made to knead at a rotation speed of 800 revolutions per minute and a revolution speed of 2000 revolutions per minute. However, even if it was operated for 30 minutes, aggregation of the substance occurred and a stable suspension could not be obtained.
As a result of further investigations, the present inventors surprisingly put a weight like a disc-shaped stirrer in a container and tried to suspend it in the same manner. It has been found that a uniform and stable suspension can be produced.

That is, the present invention provides a container in which a required amount of medium and an object to be processed and a “weight” are placed in a container installed in a container holder of a rotation / revolution type defoaming and kneading apparatus. The present invention relates to a method of installing in a container holder, causing the container to rotate and revolve by the rotation and revolution type defoaming kneading apparatus, kneading the object to be processed and the medium in the container, and uniformly dispersing the object to be processed in the medium.
In addition, the present invention is to rotate and revolve the container installed in the container holder of the rotation and revolution type defoaming and kneading apparatus by the rotation and revolution type defoaming and kneading apparatus to knead the workpiece and the medium in the container, The present invention relates to a “weight” for placing in a container installed in a container holder of the rotation / revolution type defoaming kneading apparatus for uniformly dispersing an object to be processed in the container in a medium.
Furthermore, the present invention is installed in a container holder of a rotation and revolution type defoaming kneading apparatus for uniformly dispersing an object to be processed in a medium, which contains the above-described “weight” of the present invention in a container. Related to the container.
In addition, the present invention is to rotate and revolve the container installed in the container holder of the rotation and revolution type defoaming and kneading apparatus by the rotation and revolution type defoaming and kneading apparatus to knead the workpiece and the medium in the container, The present invention relates to the use of a “weight” that is placed in a container installed in a container holder of the rotation and revolution type defoaming kneading apparatus for uniformly dispersing an object to be processed in the container in a medium.

The present invention will be described in more detail as follows.
(1) A container in which a required amount of medium and an object to be processed and “weight” is put in a container installed in a container holder of a rotation / revolution type defoaming and kneading apparatus is used as a container holder of the rotation / revolution type defoaming and kneading apparatus. A method in which the container is rotated and revolved by the rotation / revolution type defoaming kneader to knead the object to be processed and the medium in the container to uniformly disperse the object to be processed in the medium.
(2) The method according to (1), wherein the weight is a metal.
(3) The method according to (2), wherein the metal is iron or copper.
(4) The method according to any one of (1) to (3), wherein the weight is covered with a flexible plastic.
(5) The method according to (4), wherein the flexible plastic is Teflon (registered trademark).
(6) The method according to any one of (1) to (5), wherein the weight shape is substantially cylindrical.
(7) The method according to (6), wherein the ratio of the diameter of the substantially cylindrical weight to the inner diameter of the container is 0.2 to 0.8.
(8) The method according to any one of (1) to (7), wherein the object to be treated is pulverized and / or kneaded with a weight placed in a container to adjust the particle diameter.
(9) The method according to any one of (1) to (8), wherein the medium is a liquid.
(10) The method according to (9), wherein the dispersion of the object to be processed in the liquid medium is suspension.
(11) The method according to (9) or (10) above, wherein the liquid medium contains a dispersion medium.
(12) The method according to any one of (9) to (11), wherein the liquid medium is water or water containing an aqueous dispersion medium.
(13) The method according to (11) or (12), wherein the dispersion medium is one or more compounds selected from a salt of carboxymethylcellulose, hydroxypropylmethylcellulose, and methylcellulose.
(14) The method according to any one of (11) to (13), wherein the dispersion medium is carboxymethylcellulose sodium salt.
(15) The method according to any one of (1) to (14), wherein the object to be processed is a hydrophobic substance.
(16) The method according to any one of (1) to (15), wherein the object to be processed is a pharmaceutical product.
(17) A dispersion in which an object to be processed produced by the method according to any one of (1) to (16) is uniformly dispersed in a medium.
(18) The dispersion according to (17), wherein a 50% particle diameter of the object to be treated is 100 μm or less and a 90% particle diameter is 200 μm or less.
(19) The dispersion according to (17), wherein a 50% particle diameter of the object to be treated is 50 μm or less and a 90% particle diameter is 100 μm or less.
(20) The dispersion according to any one of (17) to (19), wherein the medium is a liquid and the dispersion is a suspension.
(21) The container installed in the container holder of the rotation / revolution type defoaming kneading apparatus is rotated and revolved by the rotation / revolution type defoaming kneading apparatus to knead the object to be treated and the medium in the container, A weight for placing in a container installed in a container holder of the rotation / revolution type defoaming kneading apparatus for uniformly dispersing the object to be processed in the medium.
(22) The weight according to (21), wherein the weight is a metal.
(23) The weight according to (22), wherein the metal is iron or copper.
(24) The weight according to any one of (21) to (23), wherein the weight is covered with a flexible plastic.
(25) The weight according to (24), wherein the flexible plastic is Teflon (registered trademark).
(26) The weight according to any one of (21) to (25), wherein the weight has a substantially cylindrical shape.
(27) The weight according to (26), wherein the ratio of the diameter of the substantially cylindrical weight to the inner diameter of the container is 0.2 to 0.8.
(28) The weight according to any one of (21) to (27), wherein the medium is a liquid.
(29) A rotation and revolution type defoaming and kneading apparatus for uniformly dispersing an object to be processed in a medium, comprising the “weight” according to any one of (21) to (28) in a container. A container installed in a container holder.
(30) The container installed in the container holder of the rotation / revolution type defoaming kneading apparatus is rotated and revolved by the rotation / revolution type defoaming kneading apparatus to knead the object to be processed and the medium in the container, and in the container Use of a “weight” placed in a container installed in a container holder of the rotation / revolution type defoaming kneader to uniformly disperse the object to be processed in the medium.
(31) The use according to (30), wherein the weight is the weight described in any of (21) to (28).

Further, the “use” of the present invention will be described in detail as follows.
(32) A kneading aid for uniformly dispersing the object to be processed having the weight according to any one of (21) to (28) in a medium.
(33) The kneading aid according to (32), wherein the weight is a metal.
(34) The kneading aid according to claim 2, wherein the metal is iron or copper.
(35) The kneading aid according to any one of (32) to (34), wherein the weight is covered with a flexible plastic.
(36) The kneading aid according to (35), wherein the flexible plastic is Teflon (registered trademark).
(37) The assisting tool for kneading according to any one of (32) to (36), wherein the weight is substantially cylindrical.
(38) The kneading aid according to (37), wherein the ratio of the substantially cylindrical weight diameter to the inner diameter of the container is 0.2 to 0.8.
(39) For kneading according to any one of (32) to (38), wherein the object to be treated is pulverized and / or kneaded by a weight placed in a container to adjust the particle diameter. Auxiliary tool.
(40) The kneading aid according to any one of (32) to (39), wherein the medium is a liquid.
(41) The kneading aid according to (40), wherein the dispersion of the object to be processed in the liquid medium is suspension.
(42) The auxiliary tool for kneading according to any one of (32) to (41), wherein the kneading is performed by a rotation and revolution type defoaming kneader.

Next, the present invention will be described in more detail.
As described above, the “spinning and revolution type defoaming and kneading apparatus” in the present invention includes a container holder that is installed inclined with respect to the horizontal axis, and a bottomed cylindrical container that is substantially coaxially held by the container holder. The device is defined as a device that further revolves while rotating and kneads the material to be kneaded in the container by the centrifugal force of rotation and revolution. As a specific example of the “rotation and revolution type defoaming and kneading apparatus” in the present invention, a planetary gear described in Patent Document 4, in which a revolution shaft is rotationally driven by an electric motor, and the driving force of the motor is provided on the revolution shaft. An apparatus configured to transmit to a kneading container attached to the tip of a rotating arm via an apparatus and the like, and to rotate the kneading container, described in Patent Document 5, a revolution driven by an external belt A universal joint is connected to the tip of the shaft, the shaft center is inclined at an angle of about 45 °, and the cup holder that is pivotally supported at an angle of about 45 ° is driven to rotate through a driven belt at the tip. In addition, in Patent Document 9, a device which is configured as described above is provided on a rotating body attached to a substantially vertical revolution shaft and revolves around the revolution shaft, and the upper portion of the revolution shaft is on the revolution shaft side. Container holder that rotates around an inclined axis And a kneading apparatus provided with a bottomed cylindrical kneading container that is held substantially coaxially by the container holder; Patent Document 6 discloses a “fixing shaft installed in a case, and the fixing A revolving drum having a revolving drum direct coupling gear and a container mounting arm pivotably attached to a shaft, and a revolving driving gear engaged with the revolving drum direct coupling gear in the revolving drum. A drive motor, a container rotation shaft rotatably mounted on an end of the container mounting arm, a container rotation bevel gear and a container mounting portion provided on the container rotation shaft, and the public A rotation relay gear pivotally mounted on a diversion drum via a revolving / revolution cut bearing, and a rotation drive motor in which a rotation transmission drive gear is engaged with the rotation relay gear on the revolution drum; The container mounting arm is rotatable The rotation transmission shaft that is attached and one rotation transmission gear provided on the rotation transmission shaft is engaged with the rotation relay gear on the revolution drum and the other rotation transmission gear provided on the rotation transmission shaft is provided. Examples of the apparatus include a device in which a bevel gear is configured to engage with a container rotating bevel gear on the rotation axis for rotating the container. More specifically, there is a “rotation and revolution type defoaming and kneading apparatus” commercially available from Shinky Co., Ltd. under the trade name “Awatori Nertaro”, but the present invention is not limited to this.

These “spinning and revolution type defoaming and kneading apparatuses” have the following effects as described in the above-mentioned patent documents. Since the container installed in the container holder is inclined, the pressing force due to the centrifugal force acts on the inclined inner wall of the kneading container, the component force of the pressing force acts below the inner wall of the kneading container, and the kneading container rotates. In combination with the acting force, stirring and defoaming of the object to be processed are promoted. In addition, since the bottom of the kneading container is inclined with respect to the rotation axis of the container holder, the upper and lower flows are generated in the workpiece inside the container due to the rotation of the kneading container held by the container holder. Thereby, the vector of the centrifugal force generated by rotation and revolution is partially changed to an upward vector by the inclined bottom surface of the container, and a convective flow is obtained. Therefore, since the objects to be treated can be effectively stirred and kneaded, even when a plurality of kinds of objects to be treated having different specific gravity are mixed and kneaded, their centrifugal separation action is prevented and uniform. It can be kneaded. Moreover, since the cylindrical side wall portion of the kneading container is disposed substantially coaxially with the rotation axis, it is possible to prevent an unbalanced rotational load from being applied to the rotation support portion that supports the container holder that holds the kneading container so as to rotate. It is possible to improve the durability by preventing the generation of vibration noise and premature uneven wear of the rotation support portion.
The description of Patent Documents 4 to 11 relating to “Rotation and revolution type defoaming and kneading apparatus” is incorporated in this specification.

As described above, the “rotation and revolution type defoaming kneading apparatus” kneads the object to be processed inside the container with a strong force by a large centrifugal force. For example, in the product description of the product name “Awatori Neritaro” “Suspension preparation can be simple and of high quality. Toxicity tests result in high doses, so frequent suspension preparations are more frequent. The suspensions of the mortars, homogenizers and mortar grinders could not be prepared, and the compounds with good wettability to water can be prepared with these conventional types, but the particle size is low. There was a tendency to be slightly smaller.With the mixing and defoaming using this machine, a suspension with good quality without any difference from the particle size of the bulk powder can be realized very easily. " Refer to the website of Awatori Nerita).
Therefore, the present inventors tried to suspend the object to be treated which is poor in “wetting” with water. As a “rotation and revolution type defoaming kneader”, “Awatori Netaro” manufactured by Shinky Co., Ltd. was used, and chloramphenicol palmitate ((2R, 3R) -2- ( An aqueous suspension of dichloroacethyl) amino-3-hydroxy-3- (4-nitrophenyl) propan-1-yl palmitate (hereinafter referred to as “chromipalmi”) was prepared. In addition, chromai palmi is a substance with poor “wetting” with respect to water.
As a result, suspension was attempted for 30 minutes, but a stable suspension could not be prepared. Since sufficient suspension cannot be achieved only by the centrifugal force of the “rotation and revolution type defoaming kneader”, the present inventors thought that it would be possible to add an action like an agate and mortar in an agate mortar. . As a result of various studies in order to reproduce such an action like a pestle and a mortar in a container that rotates at high speed, we decided to put “weight” in the container. Then, when the surface was coated with polyperfluoroethylene (Teflon (registered trademark)) and made of iron, a substantially columnar “weight” was placed in a container and experimented with the same type of “rotation and revolution type defoaming kneader”. By performing the treatment for 2 minutes 5 times, it was found that the agglomeration of the particles was suppressed and the uniformity of the suspension was remarkably improved as compared with the case where no “weight” was added. When the average particle size was measured, the 50% particle size was 45 μm, and the 90% particle size was 120 μm. In the present specification, “50% particle diameter” means a particle diameter at a position of 50% of the total number when the particles are counted from the smallest, and “90% particle diameter” When the particles are counted from the smallest, it means the particle diameter at 90% of the total number. Therefore, the smaller the 50% particle size and the smaller the difference between the 50% particle size and the 90% particle size, the better the dispersibility and uniformity of the suspension.
The average particle size is measured using a laser-type particle size distribution analyzer (HELOS & QUIXEL), measuring conditions: lens used (R5: particles less than 875μm detected), pump speed (20%), temperature (20 ° C) Measured under conditions. Moreover, you may perform evaluation by a microscope.
The results of analysis of the particle size distribution of Chromamypalmi are shown in a graph in FIG. The horizontal axis of the graph in FIG. 1 indicates the particle diameter (μm) in logarithm, and the vertical axis indicates the frequency distribution (%) and the integrated distribution (%). The convex curve shows the frequency distribution, and the increase curve shows the integrated distribution.

As described above, the details of the reason why stable suspension with uniform particle diameters has been made possible by placing “weight” in the container of the “rotation and revolution type defoaming kneader” are still fully elucidated. Although not done, an action like agate and mortar of an agate mortar occurs between the side of the “weight” placed in the container and the bottom (and wall surface) of the container. At the same time, pulverization due to the action of a mortar occurred, and it is considered that the suspension could be easily performed in a short time.
Furthermore, an experiment was conducted using 0.5% or 2% carboxymethylcellulose sodium salt (CMC-Na) as a dispersion medium. The results are shown in the following Table 1 together with the above results.

Furthermore, the result of having examined the distribution of particle diameter about the result in 2% CMC-Na is shown with a graph in FIG. The horizontal axis of the graph in FIG. 2 indicates the particle diameter (μm) in logarithm, and the vertical axis indicates the frequency distribution (%) and the integrated distribution (%). The convex curve shows the frequency distribution, and the increase curve shows the integrated distribution. As a result, it became clear that a suspension having an excellent particle size distribution can be prepared with a single peak at about 15 μm and particles of about 50 μm or more being about 5% or less. .
This result was compared with the conventional mortar method. As an object to be processed, chromi palmi was used. The results (average particle size) are shown in Table 2.

  As a result, it has been clarified that the method of the present invention can obtain almost the same result as the conventional mortar method. The conventional mortar method requires skill, and variation has occurred depending on the skill and processing method of the person to be processed, and the expert has to perform carefully and take sufficient time. It does not require skill, can be carried out reliably in a short time with good reproducibility, and the same result as the conventional mortar method can be obtained.

  Next, I tried to scale up. The particle size distribution was examined when 1 g of the workpiece was used and when 15 g was used. The results are shown in the following Table 3 and FIG.

  As a result, it was found that there was almost no difference in the average particle diameter. FIG. 3 is a graph showing the results of the particle size distribution. The horizontal axis of the graph in FIG. 3 indicates the particle size (μm) in logarithm, and the vertical axis indicates the frequency distribution (%) and cumulative distribution. (%). A thin square mark (□) (red in the original figure) indicates that the object to be processed is 1 g, and a black circle (●) (higher convex graph) (blue in the original figure) indicates that the object to be processed is 15 g . In each graph, the convex curve shows the frequency distribution, and the increase curve shows the integrated distribution. As a result, it was found that even when scaled up to about 15 times, the particle size distribution was not greatly affected, and the method of the present invention was found to be possible even with a large capacity.

Next, the “weight” shape was examined. In FIG. 4, three types of “weights” shown in photographs instead of drawings are used. That is, the left side of FIG. 4 is a substantially columnar “weight” in which the shape of the “weight” in contact with the bottom surface of the container is a substantially flat surface, and the “weight” in the center is in contact with the bottom surface of the container. The shape of the “weight” is a concavo-convex shape having protrusions and is substantially cylindrical, and the “weight” on the right side is a ball-like “weight”.
The results are shown in Table 4 below.

  As a result, it was found that the “weight” shape is preferably a substantially cylindrical shape. This is presumably because the bottom and wall surfaces of the container and the surface of the “weight” produce an action like a mortar-like pestle and mortar. For this reason, when it is in contact with the bottom surface or wall surface of the container at a point like a ball, a sufficient suspending action cannot be obtained. When they are in contact with each other, it has been found that it produces an effect like a pestle and a mortar, resulting in sufficient suspension.

Thus, the method of the present invention is characterized in that, in a conventionally used "rotation and revolution type defoaming kneading apparatus", a substantially columnar "weight" is placed in the container. Suspension with uniform particle size distribution due to the action of the weight and the bottom and side surfaces of the container and the pestle and mortar at the same time as the stirring and kneading based on the centrifugal force by the “rotation and revolution type defoaming kneader” It is characterized in that a dispersion such as a liquid can be produced easily and with good reproducibility.
As the “container” in the present invention, various containers attached to a commercially available “rotation and revolution type defoaming and kneading apparatus” can be used, but are not limited thereto.
In addition, the “weight” in the present invention is one that does not break or break the container even during the operation of the “rotation and revolution type defoaming kneading apparatus”, There is no particular limitation as long as it has a sufficient shape, material, and weight that can process the object to be processed. For this reason, the shape of the “weight” of the present invention is also related to the shape of the container. The shape of the weight is sufficient to process the workpiece by the action of the mortar on the bottom surface or the side surface of the container. Are preferred. For example, a preferable example of the “weight” in the present invention in the case where the container has a cylindrical shape includes a substantially cylindrical shape that can sufficiently contact at least the bottom surface or side surface of the container. In addition, when the shape of the container is spherical or round-bottomed like a flask, a container having a radius of curvature similar to that of the container is in great contact with the container wall. Since it has an area, it becomes a preferable shape. As is apparent from the results of Table 4 above, the “weight” of the present invention preferably has a large contact area with the bottom surface of the container. However, the “weight” is not necessarily in contact with the bottom surface of the container over the entire bottom surface of the “weight”. There is no need, and it can have irregularities as required. As the material thereof, the density in order to ensure sufficient weight 1 g / cm ³ or higher, preferably 2 g / cm ³ or more, 2 to 15 g / cm ^3, more preferably of about 3 to 10 g / cm ³ Is mentioned. Preferable materials include metals such as iron and copper. Furthermore, in order to prevent the container from being destroyed or damaged due to contact with the container, the “weight” is coated with a relatively soft material having a buffering action on its surface, particularly the part in contact with the container. Is preferred. Examples of such a covering material include plastics such as polyperfluoroethylene (Teflon (registered trademark)), polyethylene, and polystyrene. In view of chemical resistance and acid resistance, coating with polyperfluoroethylene (Teflon (registered trademark)) is preferable.

The size of the “weight” in the present invention is not particularly limited as long as it can move freely in the container, but preferably the inner diameter of the container having the diameter of the weight (the inner diameter of the container). ) Is 0.2 to 0.7, more preferably 0.3 to 0.6, or 0.4 to 0.6. As the height, the ratio of the weight height to the inner height of the container is 0.1 to 0.7, more preferably 0.2 to 0.6, 0.2 to 0.5, or About 0.2-0.4 is mentioned.
The weight of the “weight” in the present invention can be appropriately selected according to the hardness of the object to be processed and the material of the container, but is usually 0.1 to 1 times the weight of the liquid medium, preferably 0. About 2 to 0.8 times.
The “weight” of the present invention is not simply characterized by weight, but the work and medium in the container can be easily and uniformly made by the action of the pestle and the mortar on the bottom and side surfaces of the container. Are kneaded and dispersed. Therefore, the “weight” of the present invention is useful as an auxiliary tool for kneading for simply and reliably performing sufficient kneading to uniformly and stably disperse an object to be treated in a medium. It is. Such an auxiliary tool can be manufactured, sold, or used as an auxiliary tool for kneading, but as described above, its action is also related to the shape of the container, so as a set with the container. It can also be manufactured, sold or used.
There are many commercially available “revolving and revolving defoaming kneaders” for defoaming in the present invention, and they can be defoamed, but are not necessarily limited to those for defoaming. What is necessary is not to be a thing, but the container can rotate and can revolve further. Further, even if a deaerator is attached, there is no limitation as long as it can rotate and revolve. The rotation speed and revolution speed of the “spinning and revolution type defoaming kneading apparatus” of the present invention are not particularly limited, and are appropriately set according to the type and amount of the object to be processed and the type and amount of the liquid medium. be able to.

The material to be treated in the method of the present invention is not particularly limited as long as it can be dispersed or suspended in a medium, and preferably dispersion or suspension in a state where the particle size distribution is uniform is desired. For example, active ingredients such as pharmaceuticals and agricultural chemicals, foods, cosmetics and the like can be mentioned.
Further, the medium in the method of the present invention is preferably a liquid medium, but is not limited thereto, and may be used for producing a dispersion of solids. Any liquid medium may be used as long as it has fluidity and may be a highly viscous liquid. However, a more preferable liquid medium includes, but is not limited to, water such as alcohol and glycol. An organic solvent or a water-containing organic solvent may be used. If necessary, the liquid medium of the present invention may contain a dispersion medium. When the liquid medium is water, an aqueous dispersion medium is preferable as the dispersion medium. Preferred examples of the dispersion medium include carboxymethylcellulose salt, hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), and the like, and more preferred is carboxymethylcellulose sodium salt (CMC-Na).
Although there is no restriction | limiting in particular as a density | concentration of a dispersion medium, Usually, 0.1-10 mass%, Preferably about 0.2-5 mass% is mentioned.
The average particle size of the suspension of the present invention is not particularly limited. Usually, the 50% particle size is 100 μm or less, the 90% particle size is 200 μm or less, preferably the 50% particle size is 50 μm or less, 90 % Particle diameter is about 100 μm or less.
A typical example of the dispersion produced by the method of the present invention is a suspension dispersed in a liquid medium such as water, but is not limited thereto. Examples thereof include creams and ointments kneaded together, and pasty products kneaded with a resin or the like. The dispersion produced by the method of the present invention is characterized in that the dispersed solid particles have the same particle size and the particle size distribution is in a relatively narrow range. This is considered to be because the particle size distribution is homogenized during kneading by the “weight” of the present invention.

The present invention provides a simpler and more reproducible suspending method by placing “weight” in a container in a “rotation and revolution type defoaming and kneading apparatus” conventionally used. Further, the present invention provides a “weight” for this purpose, that is, the container installed in the container holder of the rotation / revolution type defoaming kneading apparatus is rotated and revolved by the rotation / revolution type defoaming kneading apparatus. For mixing the object to be processed and the liquid medium to uniformly disperse the object to be processed in the container in the liquid medium, for placing in the container installed in the container holder of the rotation and revolution type defoaming kneading apparatus It provides use as a “weight” and “weight”. Further, the present invention provides a container installed in a container holder of a rotation / revolution type defoaming kneading apparatus for uniformly dispersing an object to be processed in a liquid medium, which contains the “weight” in the container. To do.
It has been disclosed for the first time by the present invention that the “weight” of the present invention is applied to a conventional “spinning and revolution type defoaming kneading apparatus”, and the effects as disclosed by the present invention are exhibited. The invention provides a “weight” in the container of such a new and useful “rotation and revolution type defoaming kneader” and a kneading aid comprising the “weight”.

The method of the present invention provides a method for producing a suspension that is simple, short in time, good in reproducibility, stable, uniform and having a uniform particle size.
In addition, the present invention puts a “weight” in the container of the “rotation and revolution type defoaming kneader”, so that not only the conventional stirring and kneading only by centrifugal force, but also a uniform dispersion state with the same particle size. It provides a new technique to create, and a “weight” for that purpose. The method of adding the “weight” of the present invention is simple in operation, and its kneading action and sizing effect are unexpectedly remarkable, and suspensions of pharmaceuticals, agricultural chemicals, foods, cosmetics, etc. This is an extremely excellent manufacturing method.

FIG. 1 shows the particle size of chromipalmi in the suspension when 12.5 g of chromipalmi and 12.5 g of 0.5% CMC-Na aqueous solution are used as the objects to be treated. It is a graph which shows distribution. FIG. 2 shows the distribution of the particle size of chromipalmi in the suspension when 12.5 g of chromipalmi and 12.5 g of 2% CMC-Na aqueous solution are used as the objects to be treated. It is a graph to show. FIG. 3 is a graph showing the particle size distribution of chromipalmi in the suspension when the suspension is produced by the method of the present invention using 1 g or 15 g of chromipalmi as an object to be treated. FIG. 4 is a photograph replacing a drawing showing a “weight” and a container in the method of the present invention.

EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, this invention is not limited at all by these Examples.
In the following method, “Awatori Nertaro” AR-250 manufactured by Shinky Corporation was used as a “rotation and revolution type defoaming kneader”.
Experimental example 1
As an object to be treated, 1 g of chromipalmi and 200 g of 0.5% CMC-Na aqueous solution were put in a container of “Awatori Nertaro” and operated at a rotation speed of 800 rpm and a revolution speed of 2,000 rpm for 5 minutes. As a result, a uniform suspension was not obtained. The operation time was 30 minutes, but the results were the same.

As an object to be processed, 1 g of chromipalmi, 5 g of 0.5% CMC-Na aqueous solution, and a weight of 45 g covered with Teflon (registered trademark) resin, a diameter of 40 mm and a height of 17 mm are substantially columnar “weights”. Was placed in a container of “Awatori Nertaro” (inner diameter 75 mm, height 75 mm) and operated for 2 minutes at a rotation speed of 800 rpm and a revolution speed of 2,000 rpm. Furthermore, 5 g of 0.5% CMC-Na aqueous solution was added, and the operation was performed for 2 minutes. This operation was repeated, and the operation for 2 minutes was performed 5 times in total. Thereafter, 0.5% CMC-Na was added to make 50 g (drug concentration 20 mg / g). As a result, a uniform suspension having a 50% particle size of 45 μm and a 90% particle size of 120 μm was obtained. The average particle size is measured using a laser-type particle size distribution analyzer (HELOS & QUIXEL), measuring conditions: lens used (R5: particles less than 875μm detected), pump speed (20%), temperature (20 ° C) Measured under conditions. The resulting suspension was stable even after standing at 25 ° C. for 48 hours.
The results of measuring the particle size distribution of the resulting suspension are shown in FIG.

A uniform and stable suspension was obtained in the same manner as in Example 1 except that 12.5 g of chromipalmi and 500 g of 0.5% or 2% CMC-Na aqueous solution (preparation concentration 25 mg / g) were used as the objects to be treated. Obtained. However, when the 2% CMC-Na aqueous solution was used, the operation time was set to once per minute.
The results are shown in Table 1 together with the results of Example 1 described above.
The results of measuring the particle size distribution when 2% CMC-Na is used are shown in FIG.

It processed similarly to Example 1 using the same processed material as Example 1, and the same quantity. For comparison, a suspension was produced by a conventional mortar method.
Table 2 shows the results of measuring the particle size of these suspensions.

Purified water was added using 1 g or 15 g of chromipalmi as an object to be processed so that the preparation concentration thereof was 25 mg / g, and a uniform and stable suspension was obtained in the same manner as in Example 1. All of these suspensions were stable suspensions after being left at 25 ° C. for 48 hours.
The average particle diameter of each of the obtained suspensions is shown in Table 3, and the distribution of the respective particle diameters is shown in FIG.

As a “weight”, a substantially cylindrical “weight” (see the center photo in FIG. 4) having two convex protrusions on the bottom surface, or a ball-like “weight” (diameter 8 mm, spherical weight 2 g) 30) (see the photograph on the right side of FIG. 4).
The results are shown in Table 4.

The present invention provides a novel method for producing suspensions of pharmaceuticals, agricultural chemicals, foods, cosmetics, etc., and has applicability in industrial fields such as pharmaceuticals, agricultural chemicals, foods, cosmetics.
In addition, the present invention provides a novel stirring / kneading technique using “weight” and can be used in industrial fields such as chemical engineering and precision material fields that require stirring / kneading and sizing. It has sex.

Claims (31)

  In the container installed in the container holder of the rotation and revolution type defoaming kneading apparatus, a container in which the required amount of the medium and the object to be processed and "weight" is placed is installed in the container holder of the rotation and revolution type defoaming and kneading apparatus, A method of rotating and revolving the container with the rotation and revolution type defoaming kneader to knead the object to be processed and the medium in the container to uniformly disperse the object to be processed in the medium.   The method of claim 1 wherein the weight is a metal.   The method according to claim 2, wherein the metal is iron or copper.   The method according to any one of claims 1 to 3, wherein the weight is covered with a flexible plastic.   The method according to claim 4, wherein the flexible plastic is Teflon (registered trademark).   The method according to any one of claims 1 to 5, wherein the weight has a substantially cylindrical shape.   The method according to claim 6, wherein the ratio of the diameter of the substantially cylindrical weight to the inner diameter of the container is 0.2 to 0.8.   The method according to any one of claims 1 to 7, wherein the object to be treated is pulverized and / or kneaded with a weight placed in a container to adjust the particle diameter.   The method according to any one of claims 1 to 8, wherein the medium is a liquid.   The method according to claim 9, wherein the dispersion of the workpiece in the liquid medium is a suspension.   The method according to claim 9 or 10, wherein the liquid medium contains a dispersion medium.   The method according to any one of claims 9 to 11, wherein the liquid medium is water or water containing an aqueous dispersion medium.   The method according to claim 11 or 12, wherein the dispersion medium is one or more compounds selected from a salt of carboxymethyl cellulose, hydroxypropyl methyl cellulose, and methyl cellulose.   The method according to any one of claims 11 to 13, wherein the dispersion medium is carboxymethylcellulose sodium salt.   The method according to any one of claims 1 to 14, wherein the object to be processed is a hydrophobic substance.   The method according to any one of claims 1 to 15, wherein the object to be processed is a pharmaceutical product.   A dispersion in which an object to be processed produced by the method according to any one of claims 1 to 16 is uniformly dispersed in a medium.   The dispersion according to claim 17, wherein the 50% particle size of the workpiece is 100 µm or less and the 90% particle size is 200 µm or less.   The dispersion according to claim 17, wherein a 50% particle diameter of the workpiece is 50 µm or less and a 90% particle diameter is 100 µm or less.   The dispersion according to any one of claims 17 to 19, wherein the medium is a liquid and the dispersion is a suspension.   The container installed in the container holder of the rotation / revolution type defoaming kneading apparatus is rotated and revolved by the rotation / revolution type defoaming kneading apparatus to knead the object to be processed and the medium in the container, and the object to be treated in the container A weight for placing the product in a container installed in a container holder of the rotation / revolution type defoaming kneading apparatus in order to uniformly disperse the substance in the medium.   The weight according to claim 21, wherein the weight is a metal.   The weight according to claim 22, wherein the metal is iron or copper.   The weight according to any one of claims 21 to 23, wherein the weight is covered with a flexible plastic.   The weight according to claim 24, wherein the flexible plastic is Teflon (registered trademark).   The weight according to any one of claims 21 to 25, wherein the weight has a substantially cylindrical shape.   27. The weight according to claim 26, wherein the ratio of the substantially cylindrical weight diameter to the inner diameter of the container is 0.2 to 0.8.   28. The weight according to any one of claims 21 to 27, wherein the medium is a liquid.   A rotation and revolution type defoaming kneading apparatus for uniformly dispersing an object to be processed in a medium, comprising the “weight” according to any one of claims 21 to 28 in a container. Container installed in the container holder.   The container installed in the container holder of the rotation / revolution type defoaming kneading apparatus is rotated and revolved by the rotation / revolution type defoaming kneading apparatus to knead the object to be processed and the medium in the container, and the object to be treated in the container Use of a “weight” placed in a container installed in a container holder of the rotation / revolution type defoaming kneading apparatus in order to uniformly disperse an object in a medium   The use according to claim 30, wherein the weight is the weight described in any one of claims 21 to 28.