WO2013061824A1

WO2013061824A1 - Mixing system

Info

Publication number: WO2013061824A1
Application number: PCT/JP2012/076688
Authority: WO
Inventors: 丹　誠一; 榎村　眞一
Original assignee: クリーンメカニカル株式会社; エム・テクニック株式会社
Priority date: 2011-10-27
Filing date: 2012-10-16
Publication date: 2013-05-02
Also published as: JP2013094683A; JP5542107B2

Abstract

[Problem] To provide a mixing system which can be installed in a saved space and is suitable for manufacturing a pharmaceutical solution. [Solution] A mixing system is provided with a first line in which a first flow rate regulating valve is provided in a pipe line for causing a concentrated solution to flow therethrough, a second line in which a second flow rate regulating valve is provided in a pipe line for causing a diluted solution to flow therethrough, a third line for causing a mixed solution to flow therethrough, and a mixer connected to the first to third lines. The first line regulates the flow rate of the concentrated solution by the first flow rate regulating valve and sends the concentrated solution to the mixer, the second line regulates the flow rate of the diluted solution by the second flow rate regulating valve and sends the diluted solution to the mixer, and the mixer mixes the concentrated solution and the diluted solution and continuously sends the mixed mixed solution to the third line without the mixed solution staying therein.

Description

Mixing system

The present invention relates to a mixing system for preparing foods such as pharmaceutical solutions and beverages by mainly mixing concentrated liquid and diluent.

Many pharmaceuticals and foods require quality maintenance in their production, and their production facilities require regular cleaning and sterilization operations. In particular, biological products such as biologics and blood products (pharmaceutical solutions) are kept at a constant temperature so as not to cause activities such as the growth of bacteria, and the production equipment is periodically washed with washing water, Sterilized with high-temperature pure steam.

For example, in the production of injection solutions, a batch-type injection solution production system as shown in FIG. 5 is known. The injection liquid production system 90 includes a preparation tank 91,

pumps

93 a and 93 b, a cooler 94, a filter 95, and a liquid storage tank 96. In the injection solution manufacturing system 90, the preparation tank 91 has a stirrer 92 therein. First, a predetermined amount of water for injection W9 and a raw material R9 for injection solution are respectively put into the preparation tank 91 and injected by the stirrer 92. Prepare liquid M9. Thereafter, the injection solution M9 is passed through the cooler 94 and the filter 95 by the pump 93a and sent to the liquid storage tank 96. Thereafter, the injection solution S9 in the liquid storage tank 96 is sent to the filling machine or a predetermined place by the pump 93b. Thus, since this injection solution manufacturing system 90 completes processing for each process (preparation, filtration sterilization, transportation, filling, etc.), there is an advantage that quality control, cleaning and sterilization operations can be performed relatively easily. is there.

When a small amount of pharmaceutical solution is required, it has been proposed to prepare a pharmaceutical solution directly at the medical site. In Patent Document 1, as a device for preparing a pharmaceutical solution in a short time, a pharmaceutical solution is prepared by merging an active ingredient concentrate and a dilution medium with a pump or the like, and the pharmaceutical solution is supplied to a patient via a filter and a nozzle. An infusion device is described. Patent Document 2 discloses a device for diluting a reagent used in an IC factory or the like in a field other than a pharmaceutical solution, where a reagent stock solution and a diluting solvent are combined with a mixing pipe by a pump and mixed and diluted to a predetermined concentration. An apparatus for feeding liquid is described.

International Publication No. 99/32175 JP-A-6-31148

However, in the batch-type injection solution manufacturing system, it is necessary to temporarily store all the injection solutions for each process, and therefore, the preparation tank and the storage tank have a large capacity. Moreover, in the batch type injection solution manufacturing system, since the injection solution takes time and cost, the injection solution inevitably tends to be expensive.

The device for preparing a pharmaceutical solution described in Patent Document 1 does not require a large-capacity preparation tank or a storage tank, but the pharmaceutical solution is used in terms of maintaining the quality of the pharmaceutical solution and the production efficiency of the pharmaceutical solution. It is not suitable for mass production. Further, the reagent diluting device described in Patent Document 2 does not require a large-capacity preparation tank or liquid storage tank, but does not target a pharmaceutical solution. Furthermore, in the apparatus described in Patent Document 1 and Patent Document 2, since the raw material (active ingredient concentrate, reagent stock solution) and the diluent (diluent medium, diluent solvent) are mixed and diluted simply by combining, a predetermined time is required. The quality of the manufactured pharmaceutical solution greatly depends on the manufacturing conditions such as the environment and the combination of the raw material and the diluent. Therefore, it is unsuitable for manufacturing a large amount of pharmaceutical solution.

The above increase in the capacity of the blending tank and the increase in manufacturing cost were the same for the manufacturing system for manufacturing foods such as beverages.

The present invention has been made in consideration of the above points, and an object thereof is to provide a mixing system suitable for the production of foods such as pharmaceutical solutions and beverages.

The mixing system according to the present invention includes a first line in which a first flow rate adjustment valve is provided in a conduit through which the concentrate is circulated, and a second flow rate adjustment valve is provided in a pipeline in which the diluent is circulated. And a mixer connected to each of the first to third lines, the first line comprising: a second line configured to circulate the liquid mixture; The flow rate of the concentrate is adjusted by the flow rate adjustment valve of 1 and the concentrate is sent to the mixer. The second line is diluted by the flow rate of the dilution solution by the second flow rate adjustment valve. The liquid is fed, and the mixer is characterized in that the concentrated liquid and the diluting liquid are mixed and the mixed liquid is continuously fed to the third line without staying inside.

This configuration allows the entire mixing system to be miniaturized and installed in a space-saving manner. In particular, preparation tanks used in batch systems and the like are large in size because it is necessary to prepare and store a concentrated solution and a diluted solution at a time, but this preparation tank can be made unnecessary. A small tank can be used as a liquid storage tank for storing the concentrated liquid and the diluted liquid. In addition, if a supply source for the concentrated liquid and the diluted liquid and a liquid destination for the mixed liquid are prepared in advance, a tank for storing the concentrated liquid, the diluted liquid, and the mixed liquid is not necessarily provided at the manufacturing site. They do not have to be prepared and can be dispensed with.

Also, the manufacturing time of the mixed liquid can be shortened, and the cost for maintaining the quality of the mixed liquid can also be reduced. As a result, the liquid mixture can be manufactured at low cost.

As described above, according to the mixing system of the present invention, since a mixed solution can be continuously produced from a concentrated solution and a diluted solution in a series of flows, a large preparation tank that is required in a batch method is unnecessary. can do. Therefore, the whole mixing system can be reduced in size and installed in a space-saving manner. Moreover, the manufacturing time of a liquid mixture can be shortened and a liquid mixture can be manufactured at low cost.

It is a schematic diagram which shows the mixing system of this embodiment. It is a figure which shows an example of the mixing system of this embodiment. It is a figure which shows an example of a mixer. It is a figure which shows the other example of the mixing system of this embodiment. It is a figure which shows the conventional manufacturing system.

FIG. 1 is a schematic diagram showing the mixing system of the present embodiment. In addition, each arrow shows the direction in which the raw material and liquid in a pipe | tube flow, respectively. The mixing system of this embodiment is a system that mainly produces a pharmaceutical solution, but can also be applied to the production of foods such as beverages. First, an outline of the entire mixing system of the present embodiment will be described with reference to FIG.

The mixing system 10 includes a preparation tank 1, a pump 3 (3a, 3b), a cooler 4, a filter 5, a liquid storage tank 6, a mixer 7, and a flow rate adjustment valve 8 (8a, 8b). Prepare. As shown in FIG. 1, these structures are connected so that the raw material R1, the dilution liquid W1, the concentrated liquid C1, and the mixed liquids M1 and S1 can each be conveyed by a pipe line.

Raw material R1 is transported to the mixing tank 1. The diluent W1 is sent to the mixer 7 via the cooler 4 and is also sent to the preparation tank 1. In order to maintain the quality of the mixed solution, in the conventional batch system manufacturing system, the mixed solution is once prepared and then the mixed solution is cooled. However, in the mixing system 10, the dilution sent to the mixer 7 is diluted. Only the liquid W1 may be cooled to adjust the temperature of the mixed liquid M1. Since the dilution liquid W1 has better cooling efficiency than the mixed liquid M1, the cooler 4 can be a small one having a cooling capacity lower than that of the conventional batch type manufacturing system.

The blending tank 1 has a stirrer 2 and stirs a predetermined amount of the raw material R1 and the diluent W1 with the stirrer 2, blends the concentrate C1, and stores the concentrate C1. The concentrated liquid C1 is sent to the mixer 7 by the pump 3a.

In the case of a conventional batch type manufacturing system, the capacity of the mixing tank and the capacity of the liquid storage tank have to be approximately the same. However, in the mixing system 10, the capacity V1 of the mixing tank 1 is relative to the diluent W1. It can be determined by the solubility of the raw material R1, and can be made smaller than the capacity V2 of the liquid storage tank 6 described later. Along with this, the stirrer 2 and the pump 3a can each be a small one having a lower capacity than that used in a conventional batch production system.

Specifically, in the conventional batch system manufacturing system, as shown in FIG. 5, all the amount of the injection liquid M9 in the preparation tank 91 is stored in the liquid storage tank 96 as (100%) injection liquid S9. In the mixing system of the present embodiment, as shown in FIG. 1, the amount of the diluting liquid W1 directly fed to the mixer 7 is 75 to 90% with respect to the total amount of the mixed liquid S1, and the liquid is fed to the mixer 7. The amount of the concentrated liquid C1 to be produced can be divided into two in advance as 10 to 25% with respect to the total amount of the mixed liquid S1, and the total amount (100%) of the mixed liquid S1 can be obtained by the mixer 7. Therefore, the preparation tank 1 can be made small. Further, the total energy required for the stirrer 2, the pump 3a, and the mixer 7 shown in FIG. 1 can be made smaller than the total energy required for the stirrer 92 and the pump 93a shown in FIG. .

The mixer 7 can mix the concentrate C1 and the diluent W1 at high speed, reliably and uniformly, and can send the mixture M1 obtained by the mixing to a predetermined line (pipe) without staying inside. Anything is acceptable. That is, the mixer 7 instantaneously mixes the concentrated liquid C1 and the diluted liquid W1 flowing at a predetermined flow rate while suppressing backflow and stagnation, and immediately sends the mixed liquid M1 to a predetermined line. Anything that does not stay inside. Such a mixer 7 can receive the concentrated solution C1 and the diluted solution W1 at a constant flow rate, and can continuously produce the mixed solution M1 as long as the concentrated solution C1 and the diluted solution W1 are supplied. . Further, the mixer 7 can be miniaturized because the storage volume of the concentrate C1, the diluent W1, and the mixture M1 can be minimized.

If such a mixer 7 is used, the time required to obtain the mixed liquid M1 from the concentrated liquid C1 and the diluted liquid W1 can be shortened, and the quality of the mixed liquid can be easily maintained. Further, by adjusting the flow rate of the concentrate C1 with the flow rate adjustment valve 8a and the flow rate of the dilution solution W1 with the flow rate adjustment valve 8b, the mixing ratio of the concentrate C1 and the dilution solution W1 can be easily set.

The mixed liquid M1 mixed by the mixer 7 is sent to the liquid storage tank 6 through the filter 5. The liquid storage tank 6 stores the liquid mixture S1. The liquid mixture S1 is sent to a predetermined place such as a filling machine or a transport device (not shown) by the pump 3b.

In the mixing system of the present embodiment, since the concentrated solution and the diluted solution are respectively sent to the mixer, the temperature of the mixed solution mixed in the mixer is set within a predetermined range by cooling only the diluted solution with good cooling efficiency. It is easy to maintain the quality inside, and the cooler used for cooling the diluted solution can be made smaller. Moreover, the pump for feeding the preparation tank, the stirrer and the concentrated liquid can be made smaller. Therefore, the entire mixing system can be installed in a space-saving manner. Moreover, in the mixing system of this embodiment, a liquid mixture can be manufactured continuously in a short time.

Next, as an example of the mixing system of the present embodiment, a mixing system for producing a pharmaceutical solution will be specifically described.

FIG. 2 is a diagram illustrating an example of the mixing system of the present embodiment. The mixing system 30 includes a preparation tank 11, a pump 13 (13a, 13b), a cooler 14, a filter 15 for filter sterilization, a liquid storage tank 16, a mixer 17, and a flow control valve 18 (18a). 18b), a flow meter 21 (21a, 21b, 21c), a pressure gauge 22 (22a, 22b, 22c), and a regulator 23 (23a, 23b). As shown in FIG. 2, these components are connected so that the drug substance R2, the injection water W2, the high-concentration drug solution C2, the mixed solution M2, and the injection solution S2 can be transported through the pipelines. Their configurations are basically the same as those described above with reference to FIG.

FIG. 3 is a diagram showing an example of a mixer. The arrows indicate the directions in which the water for injection W2, the high-concentration drug solution C2, and the mixed solution M2 flow. The mixer 17 includes an inlet 171 for allowing the injection water W2 to flow in, an inlet 172 for allowing the high concentration chemical liquid C2 to flow in, an outlet 173 for allowing the mixed liquid M2 to flow out, the injection water W2 and the high concentration chemical liquid C2. , A screen (sieving member) 175 through which the mixed liquid M2 passes under predetermined conditions, a flow path 176 that guides the mixed liquid M2 to the outlet 173, and the rotor 174. A motor 177.

As shown in FIG. 3, the mixer 17 rotates the rotor 174 at high speed with a motor 177 and mixes the water W2 for injection and the high-concentration drug solution C2. In the mixer 17, a rotor having a rotational speed of about 20,000 revolutions per minute can be used. Thereafter, the mixer 17 passes the mixed solution M2 through the screen 175 and the flow passage 176 in this order, and then flows out from the outlet 173. In addition, in the mixer 17, you may increase / decrease the number of the water for injection, the high concentration chemical | medical solution inlet, and the number of the outlets of a liquid mixture as needed.

In the mixing system 30, a washing process and a sterilization process are performed before or on a regular basis. In the washing process, the washing water flows into the mixing system 30 in the same manner as the water for injection W2, and the washing process is performed by sequentially passing through the mixer 17 and the filter 15. In the sterilization process, pure steam (high-temperature pure steam, pure steam) of 121 ° C. to 123 ° C. is generated by a pure steam generator or the like, and flows into the mixing system 30 in the same manner as the water W1 for injection. Sterilization is performed by sequentially passing the machine 17 and the filter 15. Thereafter, dry air is circulated to perform drying in the distribution channel.

Since both the amount of washing water used for the cleaning process and the amount of high-temperature pure steam used for the sterilization process are proportional to the capacity of the preparation tank 11, the capacity of the preparation tank 11 decreases as the concentration of the concentrate C2 increases. And can be made smaller than conventional batch manufacturing systems. Moreover, the temperature rising time of the mixing system 30 by the high temperature pure steam in the sterilization process can also be shortened.

In the mixing system 30, the drug substance R2 is transported to the preparation tank 11. Water for injection W <b> 2 is sent to the mixer 17 through the cooler 14 and is also sent to the preparation tank 11. In the preparation tank 11, the high-concentration drug solution C2 is prepared by stirring the drug substance R2 and the water for injection W2 with the agitator 12. Then, the water for injection W2 and the high-concentration drug solution C2 are fed to the mixer 17, respectively. At this time, the flow rates of the injection water W2 and the high-concentration drug solution C2 (flow

meters

21a and 21b) are set to predetermined flow rates, respectively, and the pressure of the injection water W2 and the high-concentration drug solution C2 (

pressure gauges

22a and 22b). To be equal. The

regulators

23a and 23b adjust the flow

rate adjusting valves

18a and 18b so that the flow rates are set in advance based on the numerical values of the

flow meters

21a and 21b. In the mixer 17, the water W2 for injection and the high concentration chemical liquid C2 are mixed at a predetermined ratio, and the mixed liquid M1 is sterilized by filtration with the filter 15 and stored in the liquid storage tank 16 as the injection S2. . Thereafter, the injection S2 is fed to a predetermined location such as a filling machine or a transport device (not shown).

In the mixing system of this embodiment, a plurality of blending tanks may be used. Moreover, you may use a powder for the raw material mixed with a diluent. It is preferable that the powder has physical properties suitable for mixing with a concentrated solution or a diluted solution.

FIG. 4 is a diagram illustrating another example of the mixing system of the present embodiment. In FIG. 4, the cooler is omitted. The mixing system 70 includes a preparation tank 51 (51a, 51b), a pump 53 (53a, 53b, 53c), a filter 55 for filter sterilization, a liquid storage tank 56, a mixer 57, and a flow rate adjustment valve 58. (58a, 58b, 58c, 58d), flow meter 61 (61a, 61b, 61c, 61d), pressure gauge 62 (62a, 62b, 62c, 62d), and regulator 63 (63a, 63b, 63c, 63d) And an ejector 64 for mainly transporting the raw material powder R5 and a measuring device 65 for measuring the powder R5. As shown in FIG. 4, those configurations are such that the drug substances R3 and R4, the raw material powder R5, the water for injection W3, the high-concentration drug solutions C3 and C4, the mixed solution M3, and the injection solution S3 can be transported through the pipelines, respectively. It is connected to the. Their configurations are basically the same as those described above with reference to FIG.

In the mixing system 70, the drug substance R3 is transported to the blending tank 51a and the drug substance R4 is transported to the blending tank 51b. The raw material powder R5 is weighed by the meter 65 and then transported by the ejector 64 to the mixer 57 by a fixed amount. Water for injection W3 is fed to the mixer 57 via a cooler (not shown), and is also sent to the flow path of the powder R5 and the mixing

tanks

51a and 51b. In the mixing tank 51a, the drug substance R3 and the water for injection W3 are mixed with the stirrer 52a to prepare the high-concentration drug solution C3. In the mixing tank 51b, the drug substance R4 and the water for injection W3 are stirred with the stirrer 52b. A high concentration chemical C4 is prepared. Then, the water for injection W3, the high-concentration drug solutions C3 and C4, and the powder R5 are fed to the mixer 57, respectively. At this time, the flow rate of the injection water W3 and the high-concentration drug solutions C3 and C4 is set to a predetermined flow rate by the

flow meters

61a, 61b, and 61c, respectively, and the injection water W3 and the high-concentration drug solution are set by the

pressure gauges

62a, 62b, and 62c. The pressures of C3 and C4 are made equal. The

regulators

63a, 63b, 63c, and 63d adjust the flow

rate adjustment valves

58a, 58b, 58c, and 58d, respectively, so that the flow rates are set in advance based on the numerical values of the

flow meters

61a, 61b, 61c, and 61d. In the mixer 57, the water W3 for injection, the high-concentration drug solutions C3 and C4, and the raw material powder R5 are mixed at a predetermined ratio, and the mixed solution M3 is sterilized by filtration with a filter 55 and stored as an injection S3. The liquid is supplied to a predetermined place such as a liquid tank 56 or a filling machine or a transport device (not shown). The injection S3 stored in the liquid storage tank 56 is sent to a predetermined place such as a filling machine or a transport device (not shown).

In the mixing system 70, a plurality of high-concentration chemical solutions and raw material powders can be mixed at a time. In the mixing system 70, the supply paths for the high-concentration chemical solution and the raw material powder can be increased or decreased as appropriate according to the application and mixing conditions.

The mixing system according to the present embodiment may be prepared in advance with a supply source for the diluted solution and the concentrated solution and a liquid destination for the mixed solution, and in this way, a storage tank for storing the preparation tank and the mixed solution. A tank can be dispensed with. Moreover, although the mixing system of the present embodiment has been described for the production of a pharmaceutical solution, it may be applied to various fields, and is particularly used for the production of foods such as beverages that require periodic cleaning of equipment. May be.

1,11 Formulation tank
2,12 Stirrer
3 (3a, 3b), 13 (13a, 13b) Pump 4, 14

Cooler

5, 15

Filter

6, 16 Liquid storage tank 7, 17 Mixer 8 (8a, 8b), 18 (18a, 18b)

Flow control valve

10, 30 Mixing system 21 (21a, 21b, 21c) Flow meter 22 (22a, 22b, 22c) Pressure gauge 23 (23a, 23b) Regulator

Claims

A first line provided with a first flow rate adjusting valve in a conduit through which the concentrate flows;
A second line provided with a second flow rate adjustment valve in a conduit through which the diluent flows;
A third line for circulating the liquid mixture;
A mixing system comprising a mixer connected to each of the first to third lines,
The first line is
While adjusting the flow rate of the concentrate with the first flow rate adjustment valve and sending the concentrate to the mixer,
The second line is
Adjusting the flow rate of the diluent with the second flow rate adjusting valve and feeding the diluent to the mixer;
The mixer is
A mixing system that mixes a concentrated solution and a diluting solution, and continuously feeds the mixed solution to the third line without staying inside.
The mixing system of claim 1, wherein the second line comprises a cooler.
Each of the first and second lines further comprises a pressure gauge,
While making the flow rate of the concentrated solution and the diluted solution respectively a predetermined flow rate,
The mixing system according to claim 1 or 2, wherein pressures of the concentrated liquid and the diluted liquid are made equal.
The mixing system according to any one of claims 1 to 3, comprising a plurality of the first lines.
A fourth line for distributing powder;
The fourth line comprises a meter;
The mixing system according to any one of claims 1 to 4, wherein the amount of powder is adjusted by the measuring device and the powder is transported to the mixer.