WO2021132465A1

WO2021132465A1 - System for manufacturing paste preparation and method for manufacturing paste preparation

Info

Publication number: WO2021132465A1
Application number: PCT/JP2020/048457
Authority: WO
Inventors: 弘旭本田; 一帆石瀬; 悠河崎; 佐藤　真一; 淳子一谷; 田中　修; 後藤　博
Original assignee: ライオン株式会社
Priority date: 2019-12-27
Filing date: 2020-12-24
Publication date: 2021-07-01
Also published as: JPWO2021132465A1; CN114514066A

Abstract

This system for manufacturing a paste preparation comprises a powder mixing device (50), a mixing device (1) for mixing a powder with a liquid, said mixing device being provided with a homogenizer (20) and a tank body (12), and a supply means for supplying a mixed powder obtained in the powder mixing device (50) to the mixing device (1). This method for manufacturing a paste preparation comprises a mixing step for mixing a starting powder material containing a binder with a starting liquid material using the mixing device (1), said mixing device being provided with the homogenizer (20) and the tank body (12), wherein the mixing step involves a procedure for mixing a mixed powder, said mixed powder having a ratio by volume represented by [whole or part of starting powder material excluding binder]/[binder] of 0.3 or greater, with the starting liquid material.

Description

Manufacturing system of paste-like preparation and manufacturing method of paste-like preparation

The present invention relates to a paste-like preparation production system and a paste-like preparation production method.
This application claims priority based on Japanese Patent Application No. 2019-237962 filed in Japan on December 27, 2019, the contents of which are incorporated herein by reference.

Paste-like preparations such as dentifrices, conditioners, treatments and skin creams have high viscosities. Therefore, a mixing device having a homogenizer is widely used for producing a paste-like preparation.
Generally, the paste-like preparation contains a binder. Simply mixing the binder with the liquid material in a mixer can result in "lumps", i.e., lumps of the binder that are not completely dissolved. When such a lump called "lump" is generated, it takes time to uniformly disperse the binder, and it is necessary to redo the work.
To solve these problems, a method for producing a dentifrice composition has been proposed in which the vacuum compounding tank in which the liquid raw material is charged is depressurized and the powder raw material is sucked and introduced into the liquid of the vacuum compounding tank under reduced pressure (patented). Document 1).

Japanese Unexamined Patent Publication No. 11-189518

However, the conventional technique has not yet sufficiently prevented the formation of the above-mentioned "lumps".
Therefore, an object of the present invention is a system for producing a paste-like preparation and a method for producing a paste-like preparation, which can prevent the formation of lumps of "lumps" in which the binder is not completely dissolved.

The present invention has the following aspects.
<1> Powder mixer and
A mixing device with a homogenizer and a tank body,
A supply means for supplying the mixed powder obtained by the powder mixing device to the mixing device, and
Manufacturing system for paste-like preparations.

<2> A mixing device having a homogenizer and a tank body, which has a mixing step of mixing a powder raw material containing a binder with a liquid raw material.
In the mixing step, a mixed powder having a volume ratio of 0.3 or more represented by [a part or all of the powder raw material other than the binder] / [the binder] is mixed with the liquid raw material. A method for producing a paste-like preparation, which comprises an operation for producing a paste-like preparation.
<3> In the mixing step, a mixed powder having a volume ratio of 0.3 or more represented by [a part of the powder raw material other than the binder] / [the binder] is used as the liquid raw material. The method for producing a paste-like preparation according to <2>, which comprises an operation of mixing and then mixing the rest of the powder raw material with the liquid raw material.
<4> In the mixing step, the contents in the tank body are extracted from the tank body by the homogenizer, and then the extracted contents are supplied into the tank body and obtained by the powder mixing device. The method for producing a paste-like preparation according to <2> or <3>, wherein the mixed powder is added to the liquid raw material.
<5> The discharge speed α of the content to be extracted from the tank body by the homogenizer is 5 L / min or more.
The rate β of addition of the mixed powder to the liquid raw material is 200 kg / min or less.
The method for producing a paste-like preparation according to <4>, which satisfies any of the following conditions (1) to (3).
Condition (1): When the loosening bulk density of the powder other than the binder is less than 0.1 g / mL, α / β ≧ 5 L / kg.
Condition (2): When the loosening bulk density of the powder other than the binder is 0.1 g / mL or more and less than 0.3 g / mL, α / β ≧ 3.5 L / kg.
Condition (3): When the loosening bulk density of the powder other than the binder is 0.3 g / mL or more, α / β ≧ 2.5 L / kg.

According to the paste-like preparation production system and the paste-like preparation production method of the present invention, it is possible to prevent the formation of "lumps" in which the binder is not completely dissolved and becomes lumps.

It is a schematic diagram which shows an example of the manufacturing system of the paste-like preparation. It is a figure which shows an example of a homogenizer, and is the sectional view in the direction orthogonal to the central axis of a fixed blade and a rotary blade. It is a figure which shows an example of a homogenizer, and is the cross-sectional view in the direction along the central axis of a fixed blade and a rotary blade.

(Paste-like preparation)
A paste-like preparation is a preparation in which a powder raw material is dispersed in a liquid raw material.
In the present invention, the paste-like preparation is a sol-like or gel-like preparation, for example, a dentifrice, a conditioner, a treatment, a skin cream, and the like.

The powder raw material is not particularly limited as long as it contains a binder, and is appropriately selected depending on the type of the paste-like preparation.
When the paste-like preparation is a dentifrice, the raw materials are, for example, powder raw materials such as abrasives, binders, solid surfactants, powder sweeteners, preservatives, powder wetting agents and powder medicinal ingredients, and liquids. It is a liquid raw material such as a surfactant, a liquid sweetener, a fragrance, a liquid wetting agent and water.
The "powder raw material" is a raw material that is a powder in an environment of room temperature (15 to 25 ° C.). A "liquid raw material" is a raw material that is liquid in an environment at room temperature.

The binder is an organic water-soluble polymer. The water-soluble means the solubility of the solute in water, and the organic water-soluble polymer is a polymer that dissolves in water at 100 mass ppm or more under the conditions of pH 7 and 25 ° C. A polymer is a compound having a weight average molecular weight of 1000 or more. The weight average molecular weight is a value measured by gel permeation chromatography.
Examples of the organic water-soluble polymer include cellulose derivatives such as sodium carboxymethyl cellulose, methyl cellulose and hydroxyethyl cellulose, alkali metal alginates such as carrageenan and sodium alginate, gums such as xanthan gum, tragacanth gum, galaya gum and arabic gum, polyvinyl alcohol and polyvinyl. Synthetic binders such as pyrrolidone, sodium polyacrylate, and carboxyvinyl polymer. If it is a binder composed of these organic water-soluble polymers, it swells in water and dissolves. The binder may be used alone or in combination of two or more.
The average particle size of the binder is preferably, for example, 1 to 500 μm, more preferably 10 to 200 μm. When the average particle size of the binder is equal to or higher than the above lower limit, the binder is less likely to be completely dissolved and lumps are less likely to occur. When the average particle size of the binder is not more than the above upper limit, it is easily dissolved in water. The "average particle size" is a value obtained by arithmetically averaging the particle sizes of 10,000 randomly selected granular dosage forms (number average).
The loosening bulk density is, for example, preferably 0.1 to 1.0 g / mL, more preferably 0.2 to 0.8 g / mL.
The loose bulk density is the apparent density at the time of sparse filling of the powdered drug. More specifically, the loose bulk density is the ratio of the mass of the powder sample in the untapped (loose) state to the volume of the powder containing the factor of the interparticle void volume. Sparse filling is the gentle filling of powder into a container without consolidation.
The loose bulk density is the measurement method of "bulk density" in "3.01 bulk density and tap density measurement method" of the three pharmacopoeias (Japanese Pharmacopoeia, United States Pharmacopeia (USP), and European Pharmacopoeia (EP)). It is measured according to. Examples of the method for measuring the loose bulk density include a method using a volume meter (measurement method I) and a method using a container (measurement method II).

<Measurement method I>
≪Device≫
The device consists of an upper funnel fitted with a sieve with a mesh opening of 1.0 mm. The funnel is secured to the top of a baffle box fitted with four glass baffles that slide and bounce over the powder as it passes through. At the bottom of the baffle box is a funnel that sits directly under the box and allows powder to be collected and injected into the cup. This cup is cylindrical (volume 25.00 ± 0.05 mL, inner diameter 30.00 ± 2.00 mm) or cube (volume 16.39 ± 0.20 mL, side length 25.4 ± 0.076 mm). ..

≪Operation method≫
Minimum amount 25 cm 3 in the case of a cube ^cup, using a powder minimum amount 35 cm ³ in the case of a cylindrical cup, through the apparatus, to flow down to the overflow of excess powder in a cup serving as a receiver of the sample. At this time, move the blade of the spatula that was brought into contact with the upper surface of the cup vertically, and keep the spatula vertical to prevent consolidation and powder overflow from the cup, and excess powder from the upper surface of the cup. Carefully scrape your body. Remove all the sample from the side surface of the cup and measure the mass (m) of the powder up to 0.1% by mass. Then, the bulk density (g / mL) is calculated by the formula m / VO (VO is the volume of the cup).

<Measurement method II>
≪Device≫
The device consists of a 100 mL cylindrical container made of stainless steel.
≪Operation method≫
If necessary, 1.0 mm of sample should be sufficient to perform the test in order to crush the agglomerates formed during storage and allow the resulting sample to flow freely into the measurement vessel until it overflows. Prepare through a sieve. The excess powder is then carefully scraped off the top surface of the container. At this time, the mass (m0) of the powder is measured up to 0.1% by mass by subtracting the mass of the empty measuring container measured in advance. Then, the bulk density (g / mL) is calculated by the formula "m0 / 100".

The content of the binder with respect to the total mass of the dentifrice is, for example, preferably 0.3 to 5% by mass, more preferably 0.4 to 3% by mass.

Polishing agents include, for example, dihydrate calcium phosphate dihydrate and anhydride, tricalcium phosphate, calcium carbonate, aluminum hydroxide, alumina, insoluble sodium metaphosphate, calcium pyrophosphate, crystalline silica, amorphous silica, magnesium carbonate, etc. Inorganic powder such as magnesium phosphate and organic powder such as synthetic resin powder. These abrasives may be used alone or in combination of two or more.
The particle size of the abrasive is appropriately determined according to the required polishing effect and the like. The average particle size of the abrasive is, for example, 1 to 20 μm.
The content of the abrasive with respect to the total mass of the dentifrice is, for example, preferably 3 to 60% by mass, more preferably 4 to 40% by mass.

Wetting agents are, for example, polyhydric alcohols such as sorbitol, ethylene glycol, 1,3-butylene glycol, xylitol, trimethylglycine, reduced starch saccharified product, glycerin, propylene glycol, polyethylene glycol, polypropylene glycol, and sugar alcohols. The wetting agent may be used alone or in combination of two or more. The content of the wetting agent with respect to the total mass of the dentifrice is, for example, preferably 5 to 60% by mass, more preferably 10 to 55% by mass.

Examples of the surfactant (foaming agent) include sodium lauryl sulfate, sodium myristyl sulfate, sodium palmityl sulfate, higher fatty acids (8 to 23 carbon atoms) or salts thereof, and anionic activators such as sodium α-olefin sulfonate. Nonionic activators such as lauryl diethanolamide, sucrose fatty acid ester, polyoxyethylene sorbitan monolaurate, amphoteric activators and the like.
Liquid surfactants include polyoxyethylene sorbitan monolaurate, sucrose fatty acid ester, alkyl glugoside, polysorbitan fatty acid ester, polyoxyethylene alkyl ether sulfate, sulfosuccinate, fatty acid amide propyl dimethylaminoacetic acid betaine. , Fatty acid dimethylaminoacetic acid betaine, N-acylglutamate, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolium betaine and the like.
Examples of the powder surfactant include alkyl sulfates such as sodium lauryl sulfate, sodium myristyl sulfate, sodium palmityl sulfate, higher fatty acids (solid at 25 ° C) or salts thereof, sodium α-olefin sulfonate, and polyoxyethylene. Acrylic amino acids such as alkyl ether (solid at 25 ° C), sugar fatty acid ester, alkyl alkanolamide, polyoxyethylene sorbitan ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, N lauryl turquoise salt, lauroyl sarcosine salt, etc. Examples thereof include salts, N-acyl taurine salts such as α-olein sulfonate and lauryl methyl taurine salt, and coconut oil fatty acid amide propyl betaine.
The surfactant may be used alone or in combination of two or more.
The content of the surfactant with respect to the total mass of the dentifrice is, for example, preferably 0.1 to 7% by mass, more preferably 0.3 to 6% by mass.

Examples of the sweetener include powdered sweeteners such as sodium saccharin, sucrose, sucrose, lactose, perillartine, stebioside, glycyrrhizin salts, xylitol, aspartame, neoheseridyldihydrochalcone, acesulfame potassium, taumaten, and erythritol.
The content of the sweetener with respect to the total mass of the dentifrice is, for example, preferably 0.05 to 10% by mass, more preferably 0.1 to 9% by mass. The above-mentioned wetting agent, sorbitol, or the like may also be used as a sweetener.

Fragrances include, for example, spearmint oil, peppermint oil, salvia oil, eucalyptus oil, lemon oil, lime oil, winter green oil, cinnamon oil and other essential oils, other spices, fruit flavors, menthol, carboxylic, anetol, eugenol and the like. Peppermint or synthetic fragrance.
The content of the fragrance with respect to the total mass of the dentifrice is, for example, preferably 0.001 to 5% by mass, more preferably 0.01 to 2% by mass.

The preservative is, for example, methyl paraoxybenzoate, butyl paraoxybenzoate, or the like. Medicinal ingredients include enzymes such as dextranase, lytic enzyme, lysozyme, amylases, lytic enzymes, anti-plasmin agents such as epsilon aminocaproic acid and tranexamic acid, sodium fluoride, sodium monofluorophosphate, stannous fluoride. Fluorine compounds such as, chlorhexidine salts, quaternary ammonium salts, aluminum chlorhydroxylarantin, glycyrrhetinic acid, chlorophyll, sodium chloride, phosphoric acid compounds and the like.

The blending amount of the powder raw material is preferably 5 to 70% by mass, more preferably 6 to 50% by mass, based on the total mass of the paste-like preparation. When the blending amount of the powder raw material with respect to the total mass of the paste-like preparation is within the above range, it is easy to adjust to the desired physical properties (viscosity, etc.).

The viscosity of the paste-like preparation is, for example, preferably 20 Pa · s or more, more preferably 20 to 200 Pa · s, and even more preferably 40 to 130 Pa · s. When the viscosity of the paste-like preparation is at least the above lower limit, the shape retention is better. When the viscosity of the paste-like preparation is not more than the above upper limit, the raw materials to be blended at the time of use are easily dispersed.
The viscosity of the paste-like preparation is a value read 3 minutes after the start of measurement at 20 rpm and 25 ° C. using a single cylindrical rotary viscometer.

(Manufacturing system for paste-like preparations)
The manufacturing system for the paste-like preparation of the present invention (hereinafter, may be simply referred to as “manufacturing system”) includes a powder mixing device, a mixing device, and a supply means.
Hereinafter, the manufacturing system of the present invention will be described with reference to the drawings.

The manufacturing system 100 of FIG. 1 has a mixing device 1, a powder mixing device 50, and a powder supply pipe 52. The powder supply pipe 52 connects the mixing device 1 and the powder mixing device 50.
In the present embodiment, the powder supply pipe 52 is the “supply means”.

The mixing device 1 includes a stirring tank 10, a homogenizer 20 connected to the bottom of the stirring tank 10, and an external circulation line 40. The external circulation line 40 is located outside the stirring tank 10 and is connected to the homogenizer 20 and the upper part of the stirring tank 10.

The stirring tank 10 includes a tank main body 12, an anchor blade 14 arranged inside the tank main body 12, and a motor (not shown) for rotating the anchor blade 14. The stirring tank 10 has a decompression device for depressurizing the inside (not shown). The decompression device is, for example, a vacuum pump or the like.
The tank body 12 has a content discharge port 12a at the bottom.
The anchor wing 14 has a central portion 16 and a U-shaped portion 18.

The central portion 16 has a rotating shaft 16a arranged parallel to the height direction of the tank body 12, and a plurality of blades 16b protruding from the rotating shaft 16a toward the side wall surface of the tank body 12.
The U-shaped portion 18 includes a U-shaped shaft 18a extending upward from the tip of the rotating shaft 16a along the side wall surface of the tank body 12, a plurality of blades 18b protruding from the U-shaped shaft 18a toward the rotating shaft 16a, and a U-shape. It has a plurality of blades 18c that protrude from the shaft 18a toward the side wall surface of the tank body 12 and scrape off the side wall surface.
The central portion 16 and the U-shaped portion 18 are provided individually or together and rotatably in the same direction or in the opposite direction.

FIG. 2 is a cross-sectional view (II-II cross-sectional view of FIG. 3) in a direction orthogonal to the central axis of the fixed blade and the rotary blade provided in the homogenizer 20. FIG. 3 is a cross-sectional view (III-III cross-sectional view of FIG. 2) of the homogenizer 20 in the direction along the central axis of the fixed blade and the rotary blade.
The homogenizer 20 has a fixed portion 22, a rotating portion 32, and a motor (not shown) for rotating the rotating portion 32.

The rotating portion 32 has a rotating shaft 34, a disk-shaped rotating disk 36 provided at the upper end of the rotating shaft 34, and a rotating blade 38 extending upward from the outer peripheral edge of the rotating disk 36.
The fixing portion 22 is arranged so as to cover the upper end of the rotary blade 38, and has a ring-shaped top plate 24 having an opening 24a formed in the center and a cylindrical first fixed blade extending downward from the outer peripheral edge of the top plate 24. 26, a cylindrical second fixed blade 28 extending downward from the inner peripheral edge of the top plate 24, and an opening 30a arranged below the rotating disk 36 and serving as a bearing for the rotating shaft 34 of the rotating portion 32 are formed. It has a disc-shaped bearing plate 30 to which the lower end of the first fixing blade 26 is fixed to the outer peripheral edge.
The rotary blade 38 is located inside the first fixed blade 26 and outside the second fixed blade 28. The first fixed blade 26, the rotary blade 38, and the second fixed blade 28 are positioned coaxially with the central axis of the rotary shaft 34.

In the first fixed blade 26, wall-shaped blades 26a arranged in the circumferential direction are located at a plurality of locations equal to the circumference at intervals, and have a comb-teeth shape. The number of blades 26a is preferably 10 to 60. When the number of blades 26a is within the above range, the effect of the present invention is likely to be exhibited.
Between the two adjacent blades 26a, there are a plurality of flow paths 26b penetrating from the inside to the outside of the first fixed blade 26. The minimum width of the flow path 26b is preferably equal to or larger than the average particle size of the abrasive or the like from the viewpoint of suppressing the collapse of the abrasive or the like and ensuring the flow rate. The minimum width of the flow path 26b is preferably equal to or less than the length of the blade 26a in the circumferential direction from the viewpoint of efficiently applying a shearing force to each dosage form between the first fixed blade 26 and the rotary blade 38.
The flow path 26b is inclined in the circumferential direction (clockwise direction in FIG. 2) of the first fixed blade 26 from the inside to the outside. The inclination angle of the flow path 26b is preferably 30 to 60 degrees with respect to the radial direction of the first fixed blade 26 (0 degree). When the inclination angle of the flow path 26b is within the above range, the effect of the present invention is likely to be exhibited.

The second fixed blade 28 has wall-shaped blades 28a along the circumferential direction provided at a plurality of locations equal to the circumference at intervals, and has a comb-teeth shape. The number of blades 28a is preferably 10 to 60. When the number of blades 28a is within the above range, the effect of the present invention is likely to be exhibited.
Between the two adjacent blades 28a, there are a plurality of flow paths 28b penetrating from the inside to the outside of the second fixed blade 28. The minimum width of the flow path 28b is preferably equal to or larger than the average particle size of the abrasive or the like from the viewpoint of suppressing the collapse of the abrasive or the like and ensuring the flow rate. The minimum width of the flow path 28b is preferably equal to or less than the circumferential length of the blade 28a from the viewpoint of efficiently applying a shearing force to each dosage form between the second fixed blade 28 and the rotary blade 38.
The flow path 28b is inclined in the circumferential direction (clockwise direction in FIG. 2) of the second fixed blade 28 from the inside to the outside. The flow path 28b is inclined in the same direction as the flow path 26b of the first fixed blade 26. The inclination angle of the flow path 28b is preferably 30 to 60 degrees with respect to the radial direction of the second fixed blade 28 (0 degree). When the inclination angle of the flow path 28b is within the above range, the effect of the present invention is likely to be exhibited.

The rotary blade 38 has blades 38a extending in the radial direction provided at a plurality of locations equal to the circumference at intervals, and has a comb-teeth shape. The number of blades 38a is preferably 10 to 60. When the number of blades 38a is within the above range, the effect of the present invention is likely to be exhibited.
Between the two adjacent blades 38a, there are a plurality of flow paths 38b penetrating from the inside to the outside of the rotary blade 38. The minimum width of the flow path 38b is preferably equal to or larger than the average particle size of the abrasive from the viewpoint of suppressing the disintegration of the abrasive and ensuring the flow rate. The minimum width of the flow path 38b is the blade 26a from the point of efficiently applying a shearing force between the first fixed blade 26 and the rotary blade 38 and between the second fixed blade 28 and the rotary blade 38. It is preferable that the length is equal to or less than the circumferential length of the blade 28a and not more than the circumferential length of the blade 28a.
The flow path 38b is formed along the radial direction of the rotary blade 38.

Examples of such a mixing device 1 include "BECOMIX" (trade name) manufactured by Bernents, "DINEX" (trade name) manufactured by Fryma koruma, "Zoatec" (trade name) manufactured by AZO, and Netch Baku. Examples include "Netch Baku Mix Mixer" manufactured by Mix, "Bottom Mixer" manufactured by NPP Lab, and "UNIMIX" manufactured by Ekart.

From the middle of the external circulation line 40, a discharge line 42 for discharging the multi-drug composition from the mixing device 1 is branched. A three-way valve 44 is provided at a branch point where the discharge line 42 branches from the external circulation line 40.

The powder mixing device 50 is not particularly limited, and examples thereof include conventionally known mixing devices such as a container rotary cylindrical mixer.

One end of the powder supply pipe 52 is connected to the powder mixing device 50, and the other end is connected to the lower end of the tank body 12. The powder supply pipe 52 may be, for example, a stainless steel pipe.
A valve 54 is provided at the connection portion between the powder mixing device 50 and the powder supply pipe 52. In the present invention, the "supply means" is a powder supply pipe, but the present invention is not limited to this. The supply means may be any as long as it can supply the mixed powder to the mixing device 1, and may be, for example, a container such as a container.

(Manufacturing method of paste-like preparation)
The method for producing a paste-like preparation of the present invention (hereinafter, may be simply referred to as "production method") includes a mixing step of mixing a powder raw material containing a binder with a liquid raw material.
An embodiment of the production method of the present invention will be described with reference to FIG.
The production method of the present embodiment includes a powder mixing step and a mixing step.

First, the valve 54 is closed, the binder and a part or all of the powder raw material (arbitrary powder) other than the binder are charged into the powder mixing device 50, and these are mixed and mixed powder. (Powder mixing step). The optional powder mixed with the binder in this step (that is, a part or all of the powder raw material other than the binder) is a "diluted powder".
When the binder and a part or all of the diluted powder are charged into the powder mixing device 50, after the part or all of the diluted powder is charged from the viewpoint of suppressing the formation of the above-mentioned "lump". , It is preferable to add a binder.
The volume ratio (powder dilution ratio) represented by [diluted powder] / [caking agent] in the mixed powder is 0.3 or more. The powder dilution ratio is not particularly limited as long as it is 0.3 or more, preferably 0.5 or more, and more preferably 1.0 or more. When the powder dilution ratio in the mixed powder is at least the above lower limit value, the above-mentioned "lump" is less likely to occur in the mixing step described later, and the productivity can be improved. The volume of the powder raw material is measured by the same method as the method for measuring the loose bulk density.
The upper limit of the powder dilution ratio in the mixed powder is not particularly limited, but is preferably 5 or less, and more preferably 3 or less. When the powder dilution ratio in the mixed powder is not more than the above upper limit value, the time of the mixing step described later can be shortened and the productivity can be further improved. in addition. When the powder dilution ratio in the mixed powder is not more than the above upper limit value, it is possible to prevent the powder mixing apparatus 50 from becoming excessively large.

The diluted powder is not particularly limited, but a powder raw material that does not dissolve in the liquid raw material is preferable. The diluted powder preferably contains, for example, an inorganic powder such as an abrasive, and the inorganic powder is more preferable. As the inorganic powder of the diluted powder, an inorganic abrasive is preferable.
The average particle size of the diluted powder is preferably smaller than the average particle size of the binder, more preferably 1 to 100 μm, still more preferably 3 to 50 μm. When the average particle size of the binder is within the above range, it is possible to better prevent the above-mentioned "lump" from occurring in the mixing step described later.
The loosening bulk density of the diluted powder is preferably 0.03 to 0.9 g / mL, more preferably 0.05 to 0.7 g / mL. If the loosening bulk density is equal to or higher than the above lower limit, the productivity can be further increased. When the loosening bulk density is not more than the above upper limit value, the time of the mixing step can be shortened and the productivity can be further improved. In addition, when the powder dilution ratio is not more than the above upper limit value, it is possible to prevent the powder mixing apparatus 50 from becoming excessively large.

Part or all of the liquid raw material is charged into the tank body 12. The three-way valve 44 is switched to open the external circulation line 40. When the homogenizer 20 and the anchor blade 14 are operated, the liquid raw material (contents) in the tank body 12 is discharged from the homogenizer 20 to the outside of the tank body 12 and flows into the tank body 12 via the external circulation line 40. To do. In this way, the contents of the tank body 12 are circulated (external circulation).
The speed (discharge speed) α of the contents to be extracted from the tank body 12 by the homogenizer 20 is determined in consideration of the capacity of the tank body 12 and the like. When the capacity of the tank body 12 is 50 to 12000 L, the discharge rate α of the homogenizer 20 is preferably, for example, 5 to 20000 L / min, and more preferably 10 to 15000 L / min. When the discharge rate α is equal to or higher than the lower limit value, the mixed powder can be dispersed in the liquid raw material more quickly. When the discharge speed α is equal to or less than the upper limit value, it is possible to prevent the thickness loss due to an excessive shearing force.

When the pressure inside the tank body 12 is reduced and the valve 54 is opened, the mixed powder in the powder mixing device 50 flows into the tank body 12 via the powder supply pipe 52. The mixed powder that has flowed into the tank body 12 is mixed with the liquid raw material.

The pressure in the tank body 12 ^{is preferably 100 torr (1.33 × 10 4} Pa) to 650 torr (8.67 × 10 ⁴ Pa), preferably 150 torr (2.00 × 10 ⁴ Pa) to 550 torr (7.33 × 10). ⁴ Pa) is more preferable.

The rate β of the mixed powder added into the tank body 12 is appropriately determined in consideration of the total amount of the mixed powder, the total amount of the liquid raw materials, and the like. When the total amount of the mixed powder is 1 to 200 kg, the addition rate β of the mixed powder is preferably 200 kg / min or less, more preferably 50 kg / min or less. When the addition rate β is not more than the above upper limit value, the above-mentioned "lump" is less likely to occur. The lower limit of the addition rate β of the mixed powder into the tank body 12 is preferably 0.5 kg / min or more, and more preferably 1 kg / min or more. When the addition rate β is equal to or higher than the upper limit value, the mixed powder can be mixed with the liquid raw material in a shorter time to further improve the productivity. The addition rate β is adjusted by a combination of the opening degree of the valve 54 and the pressure in the tank body 12.

In the mixing step, when the discharge rate α is 5 L / min or more and the addition rate β is 200 kg / min or less, the ratio (α / β ratio) represented by the discharge rate α / addition rate β is the following condition (1). It is preferable to satisfy any of (3). By satisfying any one of the conditions (1) to (3), the above-mentioned "lump" is less likely to occur and the productivity can be further increased.
-Condition (1): When the loosening bulk density of the diluted powder (powder other than the binder) is less than 0.1 g / mL, α / β ≧ 5 L / kg.
-Condition (2): When the loosening bulk density of the diluted powder (powder other than the binder) is 0.1 g / mL or more and less than 0.3 g / mL, α / β ≧ 3.5 L / kg.
-Condition (3): When the loosening bulk density of the diluted powder (powder other than the binder) is 0.3 g / mL or more, α / β ≧ 2.5 L / kg.

In the condition (1), the α / β ratio is more preferably 10 L / kg or more, and further preferably 15 L / kg or more.
In the condition (2), the α / β ratio is more preferably 7 L / kg or more, further preferably 10 L / kg or more.
In the condition (3), the α / β ratio is more preferably 5 L / kg or more, and further preferably 7 L / kg or more.

The upper limit of the α / β ratio is not particularly limited, but is, for example, 300 L / kg or less. When the α / β ratio is not more than the above upper limit value, the time of the mixing step can be shortened and the productivity can be further improved.

After the mixed powder has been supplied to the tank body 12, the valve 54 is closed.

When the diluted powder is only a part of the arbitrary powder, after the operation of mixing the mixed powder and the liquid raw material (first mixing operation), the rest of the arbitrary powder is supplied to the tank body 12 and the tank is used. Mix with the contents in the main body 12 (second mixing operation). The balance of the arbitrary powder may be supplied to the tank body 12 in a plurality of times.
In the second mixing operation, the inside of the tank body 12 is depressurized, and the balance of the arbitrary powder is supplied into the tank body 12. At this time, the pressure in the tank body 12 ^{is preferably 100 to 650 torr (1.33 × 10 4} to 8.67 × 10 ⁴ Pa), preferably 150 to 550 torr (2.00 × 10 ⁴ Pa to 7.33 × 10). ⁴ Pa) is more preferable.
In the second mixing operation, the balance of the arbitrary powder may be supplied into the tank body 12 via the powder mixing device 50 and the powder supply pipe 52, or each of the optional powders may be supplied. It may be supplied into the tank body 12 from a hopper (not shown) via a pipe (not shown).
Alternatively, the balance of the arbitrary powder may be put into a container, and the balance of the arbitrary powder may be charged into the tank body 12 from this container.
The addition rate of the balance of the arbitrary powder in the second mixing operation is not particularly limited and can be appropriately determined in consideration of productivity and the like. The rate of addition of the balance of the arbitrary powder in the second mixing operation is, for example, preferably more than 200 kg / min, more preferably 300 kg / min or more. By setting the addition rate of the balance of the arbitrary powder to the above lower limit value or more, the working time of the entire mixing process can be shortened and the productivity can be further improved.

After the second mixing operation, if there is a balance of the liquid raw material, the balance of the liquid raw material is supplied to the tank body 12 so that the total amount is 100% by mass. The balance of the liquid raw material includes fragrances. By adding the fragrance as the balance of the liquid raw material, the aroma of the paste-like preparation can be further enhanced.
It is preferable that the surfactant (foaming agent) is added after the abrasive is added and then mixed. After supplying all the raw materials into the tank body 12, the inside of the tank body 12 is set to 10 to 40 torr (1.33 × 10 ³ Pa to 5.33 × 10 ³ Pa), for example, for 5 to 30 minutes. The contents of may be agitated (defoaming operation).
In this way, the powder raw material and the liquid raw material are mixed to obtain a paste-like preparation (mixing step). The defoaming operation is appropriately performed during or before and after the mixing step.

After preparing the paste-like preparation, the three-way valve 44 is switched, and the contents (paste-like preparation) in the tank body 12 are discharged from the homogenizer 20 to the outside of the tank body 12. The discharged contents are transferred to a filling machine or the like via the external circulation line 40, the three-way valve 44, and the discharge line 42 in this order.

According to the manufacturing method of the present embodiment, since the mixed powder containing the binder and the liquid raw material are mixed, the above-mentioned "lump" is unlikely to occur. Therefore, productivity can be increased.

The above-described embodiment has a powder mixing step, but the present invention is not limited thereto. A mixed powder in which the binder and the optional powder are mixed in advance may be purchased and the mixed powder may be supplied to the tank body 12.

Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited to the following description.

(Raw materials used)
<Arbitrary powder>
-Amorphous silica 1: Carplex (trade name), average particle size 10 μm, loose bulk density 0.09 g / mL, manufactured by DSL Japan Co., Ltd.
-Amorphous silica 2: Silicon dioxide A (trade name), average particle size 20 μm, loose bulk density 0.25 g / mL, manufactured by TAKI CHEMICAL CO., LTD.
-Calcium carbonate: Heavy calcium carbonate (trade name), average particle size 7 μm, loose bulk density 0.5 g / mL, manufactured by Sankyo Flour Milling Co., Ltd.
<Binder>
-Blotting agent: Xanthan gum (trade name "Monato Gum DA", manufactured by CP KolcoSan DiegoPlant Co., Ltd.) 72% by mass, sodium polyacrylate (trade name "Leogic 260", manufactured by Nippon Junyaku Co., Ltd.) 14% by mass, sodium alginate ( Product name "Sodium alginate", manufactured by Kimika Co., Ltd.) 14% by mass mixture: average particle size 80 μm, loose bulk density 0.5 g / mL.
<Other common ingredients>
-70% sorbitol liquid: manufactured by Towa Kasei Kogyo Co., Ltd.
-Propylene glycol: Made by ADEKA Corporation.
-Sodium lauryl sulfate: Made by Toho Chemical Industry Co., Ltd.
-Saccharin sodium: Made by Daito Chemical Industry Co., Ltd.
<Water>
purified water.
<Measuring method of loose bulk density>
Regarding the above loose bulk density, the loose bulk density is based on the measurement method of "bulk density" in "3.01 bulk density and tap density measurement method" of the three pharmacopoeias, and is based on the method using a container (measurement method II). Was measured.

(Examples 1-1 to 1-8)
A manufacturing system (capacity: 5000 L) similar to the manufacturing system 100 shown in FIG. 1 was used.
According to the composition shown in Table 1 below, in Examples 1-2 to 1-8, the diluted powder amorphous silica 1 and the binder were mixed in a powder mixing device for 5 minutes to obtain a mixed powder. .. The mixed powder after mixing was randomly sampled from 8 locations, and the loosening bulk density of the binder was measured at each location, and it was confirmed that the difference in the arithmetic mean value was within 15% by volume. The loosening bulk density of this amorphous silica 1 was 0.09 g / mL.
1200 kg of 70% sorbitol solution, 120 kg of propylene glycol, 8 kg of saccharin sodium, and 1612 kg of water were charged in the tank body to make the inside of the tank body 380 torr (5.07 × 10 ⁴ Pa). Under the conditions in the table, the binder or the mixed powder was supplied to the tank body at 50 kg / min while supplying the binder in Example 1-1 and the mixed powder in Examples 1-2 to 1-8 at 50 kg / min. The body and water were mixed. At this time, the rotation speed of the anchor blade was 3 m / s, and the rotation speed of the homogenizer was 25 m / s.
After supplying the entire amount of the binder or the mixed powder to the tank body, the mixing device was operated for 1 minute while maintaining the ^{inside of the tank body at 380 torr (5.07 × 10 4 Pa).}
Subsequently, in Examples 1-5, 1-11 to 1-17, 921 kg of amorphous silica 1 was newly added to the tank body, and the inside of the tank body ^{was maintained at 380 torr (5.07 × 10 4} Pa). The mixture was mixed for 1 minute. Further, in Examples 1-1 to 1-4, 1-6 to 1-8, the remaining amorphous material is 925 kg in total with the amorphous silica 1 used as the diluted powder in the previous step. Quality silica 1 was added to the tank body, and the mixture was mixed for 1 minute while maintaining the ^{inside of the tank body at 380 torr (5.07 × 10 4 Pa) in the same manner as in Example 1-5.}
Then, 60 kg of sodium lauryl sulfate was added to the tank body, and the inside of the tank body was adjusted to 30 torr (4.00 × 10 ³ Pa) and mixed for 10 minutes.
The operation of the mixing device was stopped, the contents (paste-like preparation) in the tank body were taken out, and the state of the paste-like preparation was visually evaluated according to the following evaluation criteria.

(Evaluation criteria)
◎ (excellent): The formation of “lumps” in which the binder having a diameter of 1 mm or more does not completely dissolve and becomes a lump is not observed.
◯ (Good): The formation of the above-mentioned “lumps” having a diameter of 1 mm or more and less than 10 mm is observed, but there is no problem in the quality of the composition.
Δ (possible): The above-mentioned "lumps" having a diameter of 10 mm or more and less than 30 mm are observed, but can be dispersed by passing them through a homogenizer 5 times.
X (inferior): The above-mentioned "lumps" having a diameter of 30 mm or more were observed, and uniform dispersion was not possible.

(Examples 1-11 to 1-17)
A paste-like preparation was obtained in the same manner as in Example 1-5, except that the composition and conditions shown in Table 2 below were followed. The loose bulk density of amorphous silica 1 which is the diluted powder of this example was 0.09 g / mL.
The obtained paste-like preparation was evaluated in the same manner as in Example 1-1, and the results are shown in the table below.

(Examples 2-1 to 2-4)
In Example 2-1 shown in Table 3 below, except that the composition and conditions were followed and 914 kg of amorphous silica 2 was newly added instead of 921 kg of amorphous silica 1. , Example 1-5 was obtained in the same manner as in Example 1-5. Further, in Examples 2-2 to 2-4, the balance is added so that the amount of the newly added amorphous silica 2 is 925 kg in total with the amorphous silica 2 used for diluting the binder. A paste-like preparation was obtained in the same manner as in Example 2-1 except for the above. The loose bulk density of amorphous silica 2, which is the diluted powder of this example, was 0.25 g / mL.
The obtained paste-like preparation was evaluated in the same manner as in Example 1-1, and the results are shown in the table below.

(Examples 2-11 to 2-17)
A paste-like preparation was obtained in the same manner as in Example 2-1 except that the composition and conditions shown in Table 4 below were followed. The loose bulk density of amorphous silica 2, which is the diluted powder of this example, was 0.25 g / mL.
The obtained paste-like preparation was evaluated in the same manner as in Example 1-1, and the results are shown in the table below.

(Examples 3-1 to 3-4)
In Example 3-1 shown in Table 5 below, Example 1 except that the composition and conditions were followed and 903 kg of calcium carbonate was newly added instead of 921 kg of newly added amorphous silica 1. A paste-like preparation was obtained in the same manner as in −5. Further, in Examples 3-2 to 3-4, except that the balance was added so that the newly added calcium carbonate was added to the calcium carbonate used for diluting the binder so as to add up to 925 kg. A paste-like preparation was obtained in the same manner as in 3-1.
The loose bulk density of calcium carbonate, which is the diluted powder of this example, was 0.5 g / mL.
The obtained paste-like preparation was evaluated in the same manner as in Example 1-1, and the results are shown in the table below.

(Examples 3-11 to 3-17)
A paste-like preparation was obtained in the same manner as in Example 3-1 except that the composition and conditions shown in Table 6 below were followed. The loose bulk density of calcium carbonate, which is the diluted powder of this example, was 0.5 g / mL.
The obtained paste-like preparation was evaluated in the same manner as in Example 1-1, and the results are shown in the table below.

As shown in Tables 1 to 6, in the cases where the powder dilution ratio was 0.3 or more, the evaluations were "◎ (excellent)" and "○ (good)". In the case where the powder dilution ratio was less than 0.3, the evaluation was "Δ (possible)" or "x (inferior)".

According to the paste-like preparation production system and the paste-like preparation production method of the present invention, it is possible to prevent the binder from being completely dissolved and forming lumps of "lumps", so that productivity can be improved. .. Therefore, the present invention is suitable for producing high-viscosity paste-like preparations such as dentifrices, conditioners, treatments, skin creams and the like.

1 mixing device, 10 stirring tank, 12 tank body, 12a outlet, 14 anchor blade, 16 center, 16a rotating shaft, 16b blade, 18 U-shaped part, 18a U-shaped shaft, 18b blade, 18c blade, 20 homogenizer, 22 Fixed part, 24 Top plate, 24a opening, 26 1st fixed blade, 26a blade, 26b flow path, 28 2nd fixed blade, 28a blade, 28b flow path, 30 bearing plate, 30a opening, 32 rotating part, 34 rotations Shaft, 36 rotary disk, 38 rotary blade, 38a blade, 38b flow path, 40 external circulation line, 42 discharge line, 44 three-way valve, 50 powder mixer, 52 powder supply pipe, 54 valve, 100 paste-like preparation Manufacturing system

Claims

Powder mixer and
A mixing device that has a homogenizer and a tank body and mixes powder and liquid,
A supply means for supplying the mixed powder obtained by the powder mixing device to the mixing device, and
Manufacturing system for paste-like preparations.
A mixing device having a homogenizer and a tank body, which has a mixing step of mixing a powder raw material containing a binder with a liquid raw material.
In the mixing step, a mixed powder having a volume ratio of 0.3 or more represented by [a part or all of the powder raw material other than the binder] / [the binder] is mixed with the liquid raw material. A method for producing a paste-like preparation, which comprises an operation for producing a paste-like preparation.
In the mixing step, a mixed powder having a volume ratio of 0.3 or more represented by [a part of the powder raw material other than the binder] / [the binder] is mixed with the liquid raw material. The method for producing a paste-like preparation according to claim 2, further comprising an operation of mixing the balance of the powder raw material with the liquid raw material.
In the mixing step, the contents in the tank body are extracted from the tank body by the homogenizer, and then the extracted contents are supplied into the tank body and obtained by the powder mixing device. The method for producing a paste-like preparation according to claim 2 or 3, wherein the mixed powder is added to the liquid raw material.
The discharge rate α of the contents to be extracted from the tank body by the homogenizer is 5 L / min or more.
The rate β of addition of the mixed powder to the liquid raw material is 200 kg / min or less.
The method for producing a paste-like preparation according to claim 4, which satisfies any of the following conditions (1) to (3).
Condition (1): When the loosening bulk density of the powder other than the binder is less than 0.1 g / mL, α / β ≧ 5 L / kg.
Condition (2): When the loosening bulk density of the powder other than the binder is 0.1 g / mL or more and less than 0.3 g / mL, α / β ≧ 3.5 L / kg.
Condition (3): When the loosening bulk density of the powder other than the binder is 0.3 g / mL or more, α / β ≧ 2.5 L / kg.