Method for producing paste-like preparation

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

[Technical field]

[0001] The present invention relates to a system for producing a paste-like preparation and a method for producing a paste-like preparation. This application claims priority based on Japanese Patent Application No. 2019-237962, filed on December 27, 2019, the contents of which are incorporated herein by reference. [Background technology]

[0002] Paste-like preparations such as dentifrices, conditioners, treatments, skin creams, etc., have high viscosity, and therefore, mixing devices having homogenizers are widely used for producing such paste-like preparations. Generally, paste-like preparations contain a binder. If the binder is simply mixed with the liquid raw material in a mixer, "lumps" may occur, that is, the binder does not completely dissolve and becomes lumpy. If such lumps occur, it takes time to disperse the binder evenly or the process must be redone. In response to these problems, a method has been proposed for producing a dentifrice composition in which a vacuum blending vessel containing liquid ingredients is depressurized and the powder ingredients are sucked into the liquid in the vacuum blending vessel under reduced pressure (Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 11-189518 Summary of the Invention [Problem to be solved by the invention]

[0004] However, conventional techniques have not yet been able to adequately prevent the formation of such "lumps." Therefore, an object of the present invention is to provide a system and method for producing a paste-like preparation that can prevent the formation of lumps formed when a binder does not completely dissolve. [Means for solving the problem]

[0005] The present invention has the following aspects. <1> A powder mixing device; A mixing device having a homogenizer and a tank body; A supply means for supplying the mixed powder obtained by the powder mixer to the mixer; A system for producing a paste-like formulation comprising the steps of:

[0006] <2> A mixing device having a homogenizer and a tank body includes a mixing step of mixing a powder raw material containing a binder with a liquid raw material, The method for producing a paste-like preparation, wherein the mixing step comprises an operation of mixing a mixed powder having a volume ratio represented by [part or all of the powder raw materials other than the binder] / [the binder] of 0.3 or more with the liquid raw material. <3> The mixing step includes an operation of mixing a mixed powder having a volume ratio of [a part of the powder raw material other than the binder] / [the binder] of 0.3 or more with the liquid raw material, and then mixing the remaining part of the powder raw material with the liquid raw material. <2> A method for producing the paste preparation according to claim 1. <4> The mixing step includes extracting the contents in the tank body to the outside of the tank body using the homogenizer, and then supplying the extracted contents into the tank body while adding the mixed powder obtained by the powder mixer to the liquid raw material. <2> or <3> A method for producing the paste preparation according to claim 1. <5> The discharge speed α of the content discharged from the tank body by the homogenizer is 5 L / min or more; The addition rate β of the mixed powder to the liquid raw material is 200 kg / min or less; And, any one of the following conditions (1) to (3) is satisfied: <4> A method for producing the paste preparation according to claim 1. Condition (1): If the loose bulk density of powder other than the binder is less than 0.1 g / mL, α / β ≧ 5 L / kg. Condition (2): When the loose bulk density of 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 loose bulk density of powder other than the binder is 0.3 g / mL or more, α / β≧2.5 L / kg. Effect of the Invention

[0007] According to the production system for a paste-like preparation and the production method for a paste-like preparation of the present invention, it is possible to prevent the formation of "lumps" in which the binder does not completely dissolve and forms lumps. [Brief description of the drawings]

[0008] [Figure 1] FIG. 1 is a schematic diagram showing an example of a production system for a paste-form preparation. [Diagram 2] FIG. 2 is a diagram showing an example of a homogenizer, and is a cross-sectional view in a direction perpendicular to the central axis of a fixed blade and a rotary blade. [Diagram 3] FIG. 2 is a diagram showing an example of a homogenizer, and is a cross-sectional view taken along the central axis of a fixed blade and a rotary blade. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] (Paste preparation) A paste-like preparation is a preparation in which powder ingredients are dispersed in liquid ingredients. In the present invention, the paste-like preparation is a sol- or gel-like preparation, for example, a dentifrice, a conditioner, a treatment, a skin cream, and the like.

[0010] The powder raw material is not particularly limited as long as it contains a binder, and is appropriately selected depending on the type of 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 liquid raw materials such as liquid surfactants, liquid sweeteners, flavors, liquid wetting agents, and water. The term "powdered raw material" refers to a raw material that is a powder in a room temperature environment (15 to 25° C.), and the term "liquid raw material" refers to a raw material that is a liquid in a room temperature environment.

[0011] The binder is an organic water-soluble polymer. Water solubility indicates the solubility of a solute in water, and an organic water-soluble polymer is a polymer that dissolves in water at 100 mass ppm or more under conditions of pH 7 and 25°C. The polymer is a compound with a weight-average molecular weight of 1000 or more. The weight-average molecular weight is a value measured by gel permeation chromatography. Examples of organic water-soluble polymers include cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, and hydroxyethylcellulose, alkali metal alginates such as carrageenan and sodium alginate, gums such as xanthan gum, tragacanth gum, galaya gum, and gum arabic, and synthetic binders such as polyvinyl alcohol, polyvinylpyrrolidone, sodium polyacrylate, and carboxyvinyl polymer. Binders made of these organic water-soluble polymers swell and dissolve in water. The binder may be one type alone or two or more types in combination. The average particle size of the binder is, for example, preferably 1 to 500 μm, and more preferably 10 to 200 μm. If the average particle size of the binder is equal to or greater than the lower limit, the binder is less likely to form "lumps" that are not completely dissolved and form lumps. If the average particle size of the binder is equal to or less than the upper limit, the binder is easily dissolved in water. The "average particle size" is the arithmetic average (number average) of the particle sizes of 10,000 randomly selected granular dosage forms. The loose bulk density is, for example, preferably 0.1 to 1.0 g / mL, and more preferably 0.2 to 0.8 g / mL. The loose bulk density is the apparent density of a powdered pharmaceutical when loosely packed. More specifically, the loose bulk density is the ratio of the mass of a powder sample in an untapped (loose) state to the volume of the powder including the interparticle void volume factor. Loose packing means that the powder is packed loosely in a container without compacting it. The loose bulk density is measured according to the measurement method for "bulk density" in "3.01 Bulk density and tapped density measurement method" of the three pharmacopoeias (Japanese Pharmacopoeia, United States Pharmacopoeia (USP), and European Pharmacopoeia (EP)). Examples of methods for measuring the loose bulk density include a method using a volumeter (measurement method I) and a method using a container (measurement method II).

[0012] <Measurement method I> ≪Device≫ The apparatus consists of an upper funnel fitted with a 1.0 mm sieve. This funnel is fixed to the top of a baffle box fitted with four glass baffles over which the powder slides or bounces as it passes. At the bottom of the baffle box is a funnel placed directly below the box that collects the powder and allows it to be poured into a cup. The cup is either cylindrical (volume 25.00 ± 0.05 mL, internal diameter 30.00 ± 2.00 mm) or cubic (volume 16.39 ± 0.20 mL, side length 25.4 ± 0.076 mm).

[0013] ≪How to operate≫ For cube cups, the minimum is 25cm 3 , minimum 35cm for cylindrical cups 3 The powder is allowed to flow through the apparatus into a cup that will receive the sample until the excess powder overflows. The blade of a spatula is held vertically in contact with the top of the cup and moved smoothly to carefully scrape off the excess powder from the top of the cup while keeping the spatula vertical to prevent compaction or the powder spilling out of the cup. All sample is also removed from the sides of the cup and the mass of the powder (m) is measured to the nearest 0.1% by mass. The bulk density (g / mL) is then calculated using the formula m / VO (VO is the volume of the cup).

[0014] <Measurement Method II> ≪Device≫ The apparatus consists of a stainless steel 100 mL cylindrical container. ≪How to operate≫ If necessary, a sufficient amount of sample for the test is passed through a 1.0 mm sieve to break up any agglomerates formed during storage and to allow the sample to flow freely into the measuring vessel until it overflows. Excess powder is then carefully scraped off from the top of the vessel. The mass of the powder (m0) is measured to the nearest 0.1% by subtracting the mass of the empty measuring vessel, which was previously measured. The bulk density (g / mL) is then calculated using the formula "m0 / 100".

[0015] The content of the binder relative to the total mass of the dentifrice is, for example, preferably from 0.3 to 5 mass %, and more preferably from 0.4 to 3 mass %.

[0016] Examples of the abrasive include inorganic powders such as dibasic calcium phosphate dihydrate and anhydrous, tribasic calcium phosphate, calcium carbonate, aluminum hydroxide, alumina, insoluble sodium metaphosphate, calcium pyrophosphate, crystalline silica, amorphous silica, magnesium carbonate, magnesium phosphate, etc., and organic powders such as synthetic resin powder, etc. These abrasives may be used alone or in combination of two or more. The particle size of the abrasive is appropriately determined depending on the required polishing effect, etc. The average particle size of the abrasive is, for example, 1 to 20 μm. The content of the abrasive relative to the total mass of the dentifrice is, for example, preferably from 3 to 60 mass %, more preferably from 4 to 40 mass %.

[0017] Examples of the humectant include polyhydric alcohols and sugar alcohols such as sorbitol, ethylene glycol, 1,3-butylene glycol, xylitol, trimethylglycine, reduced starch saccharification products, glycerin, propylene glycol, polyethylene glycol, and polypropylene glycol. The humectant may be used alone or in combination of two or more. The content of the humectant relative to the total mass of the dentifrice is, for example, preferably 5 to 60% by mass, more preferably 10 to 55% by mass.

[0018] Examples of surfactants (foaming agents) include anionic surfactants such as sodium lauryl sulfate, sodium myristyl sulfate, sodium palmityl sulfate, higher fatty acids (having 8 to 23 carbon atoms) or salts thereof, and sodium α-olefin sulfonate; nonionic surfactants such as lauryl diethanolamide, sucrose fatty acid esters, and polyoxyethylene sorbitan monolaurate; and amphoteric surfactants. Examples of liquid surfactants include polyoxyethylene sorbitan monolaurate, sucrose fatty acid esters, alkylglucosides, polysorbitan fatty acid esters, polyoxyethylene alkyl ether sulfates, sulfosuccinates, fatty acid amidopropyl dimethylaminoacetic acid betaine, fatty acid dimethylaminoacetic acid betaine, N-acyl glutamate, and 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidarizonium betaine. Examples of powder surfactants include alkyl sulfates such as sodium lauryl sulfate, sodium myristyl sulfate, sodium palmityl sulfate, higher fatty acids (solid at 25°C) or their salts, sodium α-olefin sulfonate, polyoxyethylene alkyl ethers (solid at 25°C), sugar fatty acid esters, alkyl alkanolamides, polyoxyethylene sorbitan esters, glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, acyl amino acid salts such as N-lauroyl taurine salts and lauroyl sarcosine salts, α-olein sulfonates, N-acyltaurine salts such as lauryl methyl taurine salts, and coconut oil fatty acid amidopropyl betaine. The surfactant may be used alone or in combination of two or more kinds. The content of the surfactant relative to the total mass of the dentifrice is, for example, preferably from 0.1 to 7 mass%, and more preferably from 0.3 to 6 mass%.

[0019] Examples of sweeteners include powdered sweeteners such as saccharin sodium, sucrose, maltose, lactose, perillartine, stevioside, glycyrrhizin salts, xylitol, aspartame, neohesperidyl dihydrochalcone, acesulfame potassium, thaumatine, and erythritol. The content of the sweetener relative 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 humectant, sorbitol, etc., may also be used as the sweetener.

[0020] Examples of flavorings include essential oils such as spearmint oil, peppermint oil, salvia oil, eucalyptus oil, lemon oil, lime oil, wintergreen oil, and cinnamon oil, other spices, fruit flavors, and isolated or synthetic flavorings such as menthol, carvone, anethole, and eugenol. The content of the flavor relative to the total mass of the dentifrice is, for example, preferably from 0.001 to 5 mass%, and more preferably from 0.01 to 2 mass%.

[0021] Examples of preservatives include methyl parahydroxybenzoate, butyl parahydroxybenzoate, etc. Examples of medicinal ingredients include enzymes such as dextranase, lytic enzyme, lysozyme, amylase, and bacteriolytic enzyme, antiplasmin agents such as epsilon aminocaproic acid and tranexamic acid, fluorine compounds such as sodium fluoride, sodium monofluorophosphate, and stannous fluoride, chlorhexidine salts, quaternary ammonium salts, aluminum chlorohydroxyl allantoin, glycyrrhetinic acid, chlorophyll, sodium chloride, and phosphate compounds.

[0022] The amount of the powdery raw material to be blended relative to the total mass of the paste-form preparation is preferably 5 to 70% by mass, more preferably 6 to 50% by mass. If the amount of the powdery raw material to be blended relative to the total mass of the paste-form preparation is within the above range, it is easy to adjust the physical properties (viscosity, etc.) to the desired values.

[0023] 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. If the viscosity of the paste-like preparation is equal to or higher than the above lower limit, the shape retention is better. If the viscosity of the paste-like preparation is equal to or lower than the above upper limit, the raw materials to be blended during use are easily dispersed. The viscosity of the paste-like preparation is measured using a single cylinder type rotational viscometer at 20 rpm and 25° C., and is the value read 3 minutes after the start of measurement.

[0024] (Paste formulation manufacturing system) The production system for the paste-like preparation of the present invention (hereinafter, may be simply referred to as the "production system") comprises a powder mixer, a mixer, and a supplying means. Hereinafter, the manufacturing system of the present invention will be described with reference to the drawings.

[0025] 1 includes a mixer 1, a powder mixer 50, and a powder supply pipe 52. The powder supply pipe 52 connects the mixer 1 and the powder mixer 50. In this embodiment, the powder supply pipe 52 is the "supply means."

[0026] The mixing apparatus 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.

[0027] The stirred tank 10 includes a tank body 12, an anchor blade 14 disposed inside the tank body 12, and a motor (not shown) for rotating the anchor blade 14. The stirred tank 10 includes a pressure reducing device (not shown) for reducing the pressure inside the tank 10. The pressure reducing device is, for example, a vacuum pump. The tank body 12 has a discharge port 12a for the contents at the bottom. The anchor wing 14 has a center portion 16 and a U-section 18 .

[0028] The center portion 16 has a rotation shaft 16a arranged parallel to the height direction of the tank body 12, and a plurality of blades 16b protruding from the rotation shaft 16a towards the side wall surface of the tank body 12. The U-shaped portion 18 has 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 plurality of blades 18c protruding from the U-shaped shaft 18a toward the side wall surface of the tank body 12 and scraping the side wall surface. The central portion 16 and the U-shaped portion 18 are rotatable individually or together, and in the same or opposite directions.

[0029] Fig. 2 is a cross-sectional view (II-II cross-sectional view in Fig. 3) in a direction perpendicular 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 in Fig. 2) in a direction along the central axis of the fixed blade and the rotary blade of the homogenizer 20. The homogenizer 20 has a fixed part 22, a rotating part 32, and a motor (not shown) that rotates the rotating part 32.

[0030] 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 periphery of the rotating disk 36 . The fixed portion 22 is arranged to cover the upper end of the rotating blade 38 and comprises a ring-shaped top plate 24 with an opening 24a formed in the center, a cylindrical first fixed blade 26 extending downward from the outer peripheral edge of the top plate 24, a cylindrical second fixed blade 28 extending downward from the inner peripheral edge of the top plate 24, and a disk-shaped bearing plate 30 arranged below the rotating disc 36, having an opening 30a formed therein that serves as a bearing for the rotating shaft 34 of the rotating portion 32, and to whose outer peripheral edge the lower end of the first fixed blade 26 is fixed. The rotary blade 38 is positioned 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 rotation shaft 34.

[0031] The first fixed blade 26 has wall-like blades 26a arranged in the circumferential direction at equal intervals in a plurality of locations on the circumference, forming a comb-like shape. The number of blades 26a is preferably 10 to 60. If the number of blades 26a is within the above range, the effects of the present invention are easily achieved. Between 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 paths 26b is preferably equal to or greater than the average particle size of the abrasive, etc., in order to suppress the collapse of the abrasive, etc., and ensure a flow rate. The minimum width of the flow paths 26b is preferably equal to or less than the circumferential length of the blade 26a in order to efficiently apply a shear force to each dosage form between the first fixed blade 26 and the rotary blade 38. The flow paths 26b are 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 paths 26b is preferably 30 to 60 degrees with the radial direction of the first fixed blade 26 as the reference (0 degrees). If the inclination angle of the flow paths 26b is within the above range, the effects of the present invention are easily achieved.

[0032] The second fixed blade 28 has wall-like blades 28a arranged at equal intervals along the circumferential direction, and is comb-like. The number of blades 28a is preferably 10 to 60. If the number of blades 28a is within the above range, the effects of the present invention are easily achieved. Between 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 paths 28b is preferably equal to or greater than the average particle size of the abrasive, etc., in order to suppress the collapse of the abrasive, etc., and ensure a flow rate. The minimum width of the flow paths 28b is preferably equal to or less than the circumferential length of the blade 28a in order to efficiently apply a shear force to each dosage form between the second fixed blade 28 and the rotary blade 38. The flow paths 28b are inclined in the circumferential direction of the second fixed blade 28 (clockwise direction in FIG. 2) from the inside to the outside. The flow paths 28b are inclined in the same direction as the flow paths 26b of the first fixed blade 26. The inclination angle of the flow paths 28b is preferably 30 to 60 degrees, with the radial direction of the second fixed blade 28 as the reference (0 degrees). If the inclination angle of the flow paths 28b is within the above range, the effects of the present invention are easily achieved.

[0033] The rotary blade 38 has radially extending blades 38a provided at equal intervals at multiple locations around the circumference, forming a comb-like shape. The number of blades 38a is preferably 10 to 60. If the number of blades 38a is within the above range, the effects of the present invention are easily achieved. Between 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 paths 38b is preferably equal to or greater than the average particle size of the abrasive in order to suppress the collapse of the abrasive and ensure a flow rate. The minimum width of the flow paths 38b is preferably equal to or less than the circumferential length of the blade 26a and the circumferential length of the blade 28a in order to efficiently apply shear force to each dosage form between the first fixed blade 26 and the rotary blade 38 and between the second fixed blade 28 and the rotary blade 38. The flow passage 38b is formed along the radial direction of the rotary blade 38.

[0034] Examples of such mixing devices 1 include "BECOMIX" (product name) manufactured by Berents, "DINEX" (product name) manufactured by Fryma koruma, "Zoatec" (product name) manufactured by AZO, "Netchbacmix Mixer" manufactured by Netchbacmix, "Bottom Mixer" manufactured by NP Labs, and "UNIMIX" manufactured by Ecart.

[0035] A discharge line 42 for discharging the multi-drug composition from the mixing apparatus 1 branches off from the external circulation line 40. A three-way valve 44 is provided at the branching point where the discharge line 42 branches off from the external circulation line 40.

[0036] The powder mixer 50 is not particularly limited, and examples thereof include conventionally known mixers such as a container-rotating cylindrical mixer.

[0037] One end of the powder supply pipe 52 is connected to the powder mixer 50, and the other end is connected near 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 between the powder mixer 50 and the powder supply pipe 52. In the present invention, the "supply means" is the powder supply pipe, but the present invention is not limited to this. The supply means may be anything that can supply the mixed powder to the mixer 1, and may be, for example, a vessel such as a container.

[0038] (Method of manufacturing a paste-like preparation) The method for producing a paste-like preparation of the present invention (hereinafter, may be simply referred to as the "production method") includes a mixing step of mixing a powder raw material containing a binder with a liquid raw material. One embodiment of the manufacturing method of the present invention will be described with reference to FIG. The manufacturing method of this embodiment includes a powder mixing step and a mixing step.

[0039] First, the valve 54 is closed, and the binder and some or all of the powder raw materials other than the binder (optional powder) are charged into the powder mixer 50 and mixed to form a mixed powder (powder mixing process). The optional powder (i.e., some or all of the powder raw materials other than the binder) mixed with the binder in this process is the "diluted powder." When the binder and some or all of the dilution powder are added to the powder mixer 50, it is preferable to add the binder after adding some or all of the dilution powder in order to prevent the formation of the above-mentioned "lumps." The volume ratio (powder dilution ratio) of the mixed powder expressed by [diluted powder] / [binder] is 0.3 or more. The powder dilution ratio is not particularly limited as long as it is 0.3 or more, and is preferably 0.5 or more, and more preferably 1.0 or more. If the powder dilution ratio of the mixed powder is equal to or more than the lower limit, the above-mentioned "lumps" are less likely to occur in the mixing process described below, and productivity can be improved. The volume of the powder raw material is measured by a method similar to that 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, more preferably 3 or less. If the powder dilution ratio in the mixed powder is equal to or less than the upper limit, the time of the mixing step described below can be shortened, and the productivity can be further improved. In addition, if the powder dilution ratio in the mixed powder is equal to or less than the upper limit, the powder mixing device 50 can be prevented from becoming excessively large.

[0040] The dilution powder is not particularly limited, but is preferably a powder raw material that does not dissolve in the liquid raw material. The dilution powder preferably contains an inorganic powder such as an abrasive, and is more preferably an inorganic powder. The inorganic powder of the dilution powder is preferably an inorganic abrasive. The average particle size of the dilution powder is preferably smaller than that of the binder, more preferably 1 to 100 μm, and even more preferably 3 to 50 μm. If the average particle size of the binder is within the above range, the generation of the above-mentioned "lumps" can be more effectively prevented in the mixing step described below. The loose 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 loose bulk density is equal to or higher than the lower limit, the productivity can be further increased. If the loose bulk density is equal to or lower than the upper limit, the time of the mixing step can be shortened, and the productivity can be further improved. In addition, if the powder dilution ratio is equal to or lower than the upper limit, the powder mixer 50 can be prevented from becoming excessively large.

[0041] A part or all of the liquid raw material is put 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. In this way, the contents of the tank body 12 are circulated (external circulation). The speed (discharge speed) α of the contents discharged by the homogenizer 20 out of the tank body 12 is determined taking into consideration the capacity of the tank body 12 and the like. If the capacity of the tank body 12 is 50 to 12000 L, the discharge speed α of the homogenizer 20 is, for example, preferably 5 to 20000 L / min, more preferably 10 to 15000 L / min. If the discharge speed α is equal to or greater than the lower limit, the mixed powder can be dispersed in the liquid raw material more quickly. If the discharge speed α is equal to or less than the upper limit, viscosity reduction due to excessive shearing force can be prevented.

[0042] When the pressure inside the tank body 12 is reduced and the valve 54 is opened, the mixed powder inside the powder mixer 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.

[0043] The pressure inside the tank body 12 is 100 torr (1.33×10 4 Pa) ~ 650 torr (8.67 × 10 4Pa), and 150 torr (2.00×10 4 Pa) ~ 550 torr (7.33 × 10 4 Pa) is more preferred.

[0044] The addition speed β of the mixed powder into the tank body 12 is appropriately determined taking into consideration the total amount of the mixed powder, the total amount of the liquid raw material, and the like. If the total amount of the mixed powder is 1 to 200 kg, the addition speed β of the mixed powder is preferably 200 kg / min or less, more preferably 50 kg / min or less. If the addition speed β is equal to or less than the upper limit value, the above-mentioned "lumps" are less likely to occur. The lower limit value of the addition speed β of the mixed powder into the tank body 12 is preferably 0.5 kg / min or more, more preferably 1 kg / min or more. If the addition speed β is equal to or more than the upper limit value, the mixed powder can be mixed into the liquid raw material in a shorter time, thereby further increasing productivity. The addition speed β is adjusted by a combination of the opening of the valve 54 and the pressure inside the tank body 12.

[0045] 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) expressed by the discharge rate α / addition rate β preferably satisfies any one of the following conditions (1) to (3). By satisfying any one of the conditions (1) to (3), the above-mentioned "lumps" are further unlikely to occur and the productivity can be further increased. Condition (1): If the loose bulk density of the diluted powder (powders other than the binder) is less than 0.1 g / mL, α / β ≧ 5 L / kg. Condition (2): When the loose bulk density of the diluted powder (powders other than binders) is 0.1 g / mL or more and less than 0.3 g / mL, α / β ≧ 3.5 L / kg. Condition (3): When the loose bulk density of the diluted powder (powders other than the binder) is 0.3 g / mL or more, α / β is ≧ 2.5 L / kg.

[0046] In condition (1), the α / β ratio is more preferably 10 L / kg or more, and further preferably 15 L / kg or more. In condition (2), the α / β ratio is more preferably 7 L / kg or more, and further preferably 10 L / kg or more. In condition (3), the α / β ratio is more preferably 5 L / kg or more, and further preferably 7 L / kg or more.

[0047] The upper limit of the α / β ratio is not particularly limited, but is, for example, 300 L / kg or less. If the α / β ratio is equal to or less than the upper limit, the time for the mixing step can be shortened, and the productivity can be further improved.

[0048] After the mixed powder has been supplied to the tank body 12, the valve 54 is closed.

[0049] When the dilution powder is only a part of the optional powder, after the operation of mixing the mixed powder with the liquid raw material (first mixing operation), the remainder of the optional powder is supplied to the tank body 12 and mixed with the contents in the tank body 12 (second mixing operation). The remainder of the optional powder may be supplied to the tank body 12 in multiple batches. In the second mixing operation, the pressure inside the tank body 12 is reduced, and the remaining part of the optional powder is fed into the tank body 12. At this time, the pressure inside the tank body 12 is set to 100 to 650 torr (1.33×10 4 ~8.67×10 4 Pa), and 150 to 550 torr (2.00×10 4 Pa~7.33×10 4 Pa) is more preferred. In the second mixing operation, the remainder of the optional powder may be supplied into the tank body 12 via the powder mixer 50 and the powder supply pipe 52, or may be supplied into the tank body 12 from each supply hopper (not shown) of the optional powder via a pipe (not shown). Alternatively, the remainder of the optional powder may be placed in a container, and the remainder of the optional powder may be poured from the container into the tank body 12 . The rate of addition of the remaining optional powder in the second mixing operation is not particularly limited and can be appropriately determined taking into consideration productivity, etc. The rate of addition of the remaining optional 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 rate of addition of the remaining optional powder to the above lower limit or more, the overall working time of the mixing process can be shortened and productivity can be further improved.

[0050] If there is a remainder of the liquid raw material after the second mixing operation, the remainder of the liquid raw material is supplied to the tank body 12 so that the total amount becomes 100% by mass. The remainder of the liquid raw material can be a flavoring. By adding a flavoring as the remainder of the liquid raw material, the aroma of the paste-like preparation can be further enhanced. It is preferable to add and mix the surfactant (foaming agent) after adding the abrasive. After all the raw materials are supplied to the tank body 12, the inside of the tank body 12 is pressurized to 10 to 40 torr (1.33×10 3 Pa~5.33×10 3 The content of the tank body 12 may be stirred at a pressure of 100 MPa (Pa) for, for example, 5 to 30 minutes (degassing operation). In this manner, the powder raw material and the liquid raw material are mixed to obtain a paste-like preparation (mixing step). Note that a degassing operation is appropriately carried out during, before or after the mixing step.

[0051] After the paste-like formulation is prepared, the three-way valve 44 is switched, and the contents (paste-like formulation) 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.

[0052] According to the manufacturing method of this embodiment, since the mixed powder containing the binder is mixed with the liquid raw material, the above-mentioned "lumps" are unlikely to occur, which increases productivity.

[0053] In the above embodiment, the powder mixing step is included, 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. EXAMPLES

[0054] The present invention will be described in detail below with reference to examples, but the present invention is not limited to the following description.

[0055] (Raw materials used) <Any powder> Amorphous silica 1: Carplex (product name), average particle size 10 μm, loose bulk density 0.09 g / mL, manufactured by DSL Japan Co., Ltd. Amorphous silica 2: Anhydrous silicic acid A (product name), average particle size 20 μm, loose bulk density 0.25 g / mL, manufactured by Taki Chemical Co., Ltd. Calcium carbonate: Heavy calcium carbonate (product name), average particle size 7 μm, loose bulk density 0.5 g / mL, manufactured by Sankyo Flour Milling Co., Ltd. <Binding agent> Binder: A mixture of 72% by mass of xanthan gum (trade name "Monart Gum DA", manufactured by CP Kolco San Diego Plant Co., Ltd.), 14% by mass of sodium polyacrylate (trade name "Rheogic 260", manufactured by Nihon Junyaku Co., Ltd.), and 14% by mass of sodium alginate (trade name "Sodium Alginate", manufactured by Kimika Co., Ltd.): average particle size 80 μm, loose bulk density 0.5 g / mL. <Other common ingredients> - 70% Sorbitol solution: Manufactured by Towa Chemical Industry Co., Ltd. -Propylene glycol: Manufactured by ADEKA Corporation. -Sodium lauryl sulfate: Manufactured by Toho Chemical Industry Co., Ltd. - Sodium saccharin: Manufactured by Daito Chemical Industry Co., Ltd. <Water> Purified water. <Method of measuring loose bulk density> The loose bulk density was measured by a method using a container (measurement method II) in accordance with the measurement method for "bulk density" in "3.01 Measurement method for bulk density and tapped density" of the Third Pharmacopoeia.

[0056] (Examples 1-1 to 1-8) A production system (capacity: 5000 L) similar to the production 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 amorphous silica 1, which is a dilution powder, and the binder were mixed in a powder mixer for 5 minutes to obtain a mixed powder. The mixed powder after mixing was randomly sampled from 8 points, and the loose bulk density of the binder at each point was measured, and it was confirmed that the difference in the arithmetic mean value was within 15% by volume. The loose bulk density of this amorphous silica 1 was 0.09 g / mL. The tank was charged with 1200 kg of 70% sorbitol solution, 120 kg of propylene glycol, 8 kg of sodium saccharin, and 1612 kg of water, and the tank was pressurized to 380 torr (5.07 x 10 4 Under the conditions in the table, the binder in Example 1-1 and the mixed powder in Examples 1-2 to 1-8 were supplied to the tank body at 50 kg / min, while the binder or the mixed powder was mixed with water. 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 the entire amount of binder or mixed powder is supplied to the tank body, the inside of the tank body is heated to 380 torr (5.07×10 4 The mixer was operated for 1 minute while maintaining the pressure at 1 Pa. Next, in Examples 1-5, 1-11 to 1-17, 921 kg of amorphous silica 1 was added to the tank body, and the inside of the tank body was heated to 380 torr (5.07 × 10 4 In Examples 1-1 to 1-4 and 1-6 to 1-8, the remaining amorphous silica 1 was added to the tank body so that the total weight of the amorphous silica 1 used as the diluent powder in the previous step was 925 kg, and the tank body was pressurized to 380 torr (5.07×10 4 The mixture was mixed for 1 minute while maintaining the pressure at 1 Pa. After that, 60 kg of sodium lauryl sulfate was added to the tank body, and the inside of the tank body was pressurized to 30 torr (4.00 × 10 3 The mixture was mixed at 100° C. for 10 minutes at a pressure of 1 Pa. The operation of the mixer was stopped, the contents (paste-like preparation) in the tank body was removed, and the state of the paste-like preparation was visually evaluated according to the following evaluation criteria.

[0057] (Evaluation Criteria) ◎ (Excellent): No lumps or lumps formed from binder with a diameter of 1 mm or more where the binder does not completely dissolve are 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 with the quality of the composition. △ (Acceptable): The formation of the above-mentioned "lumps" with a diameter of 10 mm or more and less than 30 mm is observed, but they can be dispersed by passing through a homogenizer five times. × (Poor): The formation of the above-mentioned "lumps" having a diameter of 30 mm or more was observed, and uniform dispersion was impossible.

[0058] (Examples 1-11 to 1-17) A paste-form preparation was obtained in the same manner as in Example 1-5, except that the composition and conditions were as shown in the following Table 2. The loose bulk density of amorphous silica 1, which was the diluent powder in this example, was 0.09 g / mL. The obtained paste preparation was evaluated in the same manner as in Example 1-1, and the results are shown in the following table.

[0059] [Table 1]

[0060] [Table 2]

[0061] (Examples 2-1 to 2-4) In Example 2-1 shown in Table 3 below, a paste-like preparation was obtained in the same manner as in Example 1-5, 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. In addition, in Examples 2-2 to 2-4, a paste-like preparation was obtained in the same manner as in Example 2-1, except that the remainder was added so that the newly added amorphous silica 2 was 925 kg when combined with the amorphous silica 2 used for diluting the binder. The loose bulk density of the amorphous silica 2, which is the dilution powder in this example, was 0.25 g / mL. The obtained paste preparation was evaluated in the same manner as in Example 1-1, and the results are shown in the following table.

[0062] (Examples 2-11 to 2-17) A paste-form preparation was obtained in the same manner as in Example 2-1, except that the composition and conditions were as shown in the following Table 4. The loose bulk density of the diluent powder, amorphous silica 2, in this example was 0.25 g / mL. The obtained paste preparation was evaluated in the same manner as in Example 1-1, and the results are shown in the following table.

[0063] [Table 3]

[0064] [Table 4]

[0065] (Examples 3-1 to 3-4) In Example 3-1 shown in Table 5 below, a paste-like preparation was obtained in the same manner as in Example 1-5, except that the composition and conditions were followed and that 903 kg of calcium carbonate was newly added instead of 921 kg of amorphous silica 1. In addition, in Examples 3-2 to 3-4, a paste-like preparation was obtained in the same manner as in Example 3-1, except that the remainder was added so that the newly added calcium carbonate, together with the calcium carbonate used for diluting the binder, reached 925 kg. The loose bulk density of calcium carbonate, which was the diluent powder in this example, was 0.5 g / mL. The obtained paste preparation was evaluated in the same manner as in Example 1-1, and the results are shown in the following table.

[0066] (Examples 3-11 to 3-17) A paste-form preparation was obtained in the same manner as in Example 3-1, except that the composition and conditions were as shown in the following Table 6. The loose bulk density of calcium carbonate, which was the diluent powder in this example, was 0.5 g / mL. The obtained paste preparation was evaluated in the same manner as in Example 1-1, and the results are shown in the following table.

[0067] [Table 5]

[0068] [Table 6]

[0069] As shown in Tables 1 to 6, examples in which the powder dilution ratio was 0.3 or more were evaluated as "Excellent" or "Good". Examples in which the powder dilution ratio was less than 0.3 were evaluated as "Fair" or "Poor". [Industrial Applicability]

[0070] According to the system for producing a paste-like preparation and the method for producing a paste-like preparation of the present invention, it is possible to prevent the binder from being completely dissolved and forming lumps, thereby improving productivity. Therefore, the present invention is suitable for producing high-viscosity paste-like preparations such as dentifrices, conditioners, treatments, skin creams, etc. [Explanation of symbols]

[0071] 1 Mixing device, 10 Mixing tank, 12 Tank body, 12a Discharge port, 14 Anchor blade, 16 Center, 16a Rotating shaft, 16b Blade, 18 U-shaped portion, 18a U-shaped shaft, 18b Blade, 18c Blade, 20 Homogenizer, 22 Fixed portion, 24 Top plate, 24a Opening, 26 First fixed blade, 26a Blade, 26b Flow path, 28 Second fixed blade, 28a Blade, 28b Flow path, 30 Bearing plate, 30a Opening, 32 Rotating portion, 34 Rotating shaft, 36 Rotating disk, 38 Rotating blade, 38a Blade, 38b Flow path, 40 External circulation line, 42 Discharge line, 44 Three-way valve, 50 Powder mixing device, 52 Powder supply pipe, 54 Valve, 100 Paste-form preparation manufacturing system

Claims

1. A mixing device having a homogenizer and a tank body, the mixing device having a mixing step of mixing a powdered raw material containing a binder with a liquid raw material, The mixing step includes mixing a mixed powder having a volume ratio of [a portion of the powder raw material other than the binder] / [the binder] of 0.3 or more with the liquid raw material, and then mixing the remainder of the powder raw material with the liquid raw material.

2. 2. The method for producing a paste-like preparation according to claim 1, wherein the mixing step comprises extracting a content in the tank body to outside the tank body with the homogenizer, and then adding the mixed powder to the liquid raw material while supplying the extracted content into the tank body.

3. A method for producing a paste-like formulation as described in claim 2, further comprising a step of mixing the binder with a portion of the powder raw materials other than the binder in a powder mixing device to obtain the mixed powder.

4. The discharge speed α of the content discharged from the tank body by the homogenizer is 5 L / min or more; the addition rate β 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 2 or 3, which satisfies any one of the following conditions (1) to (3): Condition (1): When the loose bulk density of a powder other than the binder is less than 0.1 g / mL, α / β≧5 L / kg. Condition (2): When the loose bulk density of a 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 loose bulk density of the powder other than the binder is 0.3 g / mL or more, α / β≧2.5 L / kg.

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