TW201517896A - System for producing microneedle pharmaceutical preparation, and air-conditioning method - Google Patents

Abstract

The present invention is a system for producing a microneedle pharmaceutical preparation by coating a microneedle with a coating liquid containing a drug, and adjusting the atmospheric environment in the coating chamber for producing the microneedle pharmaceutical preparation, the system for producing the microneedle pharmaceutical preparation being equipped with: an air compressor; a moisture-permeable-film-type humidity adjustment device for adjusting the humidity of the air supplied by an air compressor, and separating the air and the water content serving as the humidity adjustment source with a moisture-permeable film; a pressure adjustment device for adjusting the pressure of the air to be supplied by the air compressor; and an air filter for removing bacteria from the air supplied to the interior of the coating chamber.

Description

Microneedle preparation manufacturing system and air conditioning method

The present invention relates to a system for producing a microneedle preparation for applying a medicament to a microneedle and an air conditioning method.

As a method for enhancing transdermal absorption of a drug, a microneedle preparation is known. A method of applying a drug to a microneedle of a microneedle preparation has a so-called immersion method (for example, Patent Document 1). This is a method in which a coating liquid containing a drug is filled in a plurality of openings formed on the barrier plate, a microneedle is inserted into the opening, and a coating liquid is applied to the microneedle. By this method, a certain amount of the coating liquid can be applied to the microneedles.

[Previous Technical Literature] [Patent Literature]

[Patent Document 1] International Publication No. 2008/139648

However, when water is used as a solvent in the coating liquid, Coating is carried out by the method disclosed in Patent Document 1, and after applying the coating liquid to the microneedles, the amount of the drug on the microneedles of the microneedle preparation obtained by the drying step is examined, and it is known that the manufacturing date or the manufacturing time is the same. Unevenness will occur, and it is quite difficult to manufacture stably.

Here, the inventors have tried to prevent application to the microneedles. The unevenness of the amount of the drug is used to lock the environment in the coating chamber where the microneedle is coated with the drug, and it is found that the physical properties of the coating liquid are suppressed by setting the coating chamber within a specific range of temperature and humidity, thereby suppressing application to the coating liquid. The amount of the drug on the microneedle is not uniform.

However, due to the internal temperature setting of the coating chamber It is quite difficult to directly control the temperature and humidity in the coating chamber by means of the device and the humidity controller. Here, the inventors of the present invention have thought that the air in the coating chamber can be maintained at a desired temperature and humidity by supplying air having a temperature and a humidity which is adjusted to a specific range outside the coating chamber to the coating chamber. The invention is achieved.

And, as described above, to adjust the coating chamber When the temperature and humidity are used to suppress the change in the physical properties of the coating liquid, it is necessary to have a relatively high humidity depending on the composition of the coating liquid. On the other hand, microneedle preparations must be manufactured under aseptic conditions. In general, in order to sterilize a certain space, a means of reducing the humidity and inhibiting the growth of microorganisms is employed. Therefore, it is considered that in the system for manufacturing a microneedle preparation, it is quite difficult to simultaneously achieve two opposite states of high humidity and sterilized state. of.

However, the inventors have found that by using a coating that will be applied The means for externally adjusting the temperature of the outside of the chamber to a specific range of temperature and humidity to be supplied into the coating chamber sufficiently satisfies the opposite requirement.

Figure 1 is based on the above points of view, and is invented by the present inventors. An example of a system for the manufacture of microneedle preparations to be considered. The microneedle preparation manufacturing 100 shown in Fig. 1 is provided with an air compressor 10, a compressed air temperature adjusting device 12 for adjusting the temperature of the air supplied from the air compressor 10, and a compressed air temperature adjusting device 12 for adjusting the temperature. The humidity adjusting device 18 for adjusting the humidity of the air and the air filter 16 for sterilizing the air supplied into the coating chamber. By using the system 100 having such a configuration, air in an aseptic state that has been previously adjusted to a specific range of temperature and humidity is supplied into the coating chamber, whereby the coating chamber can be maintained in a desired air environment. When the air environment in the coating chamber is a specific range of temperature and humidity, the physical property change of the coating liquid in the coating chamber can be suppressed. Therefore, in this environment, the unevenness of the amount of the drug applied to the microneedles is also suppressed.

On the other hand, because of the coating liquid applied to the microneedle preparation In order to suppress the change in the physical properties of the coating liquid, it is necessary to set the coating chamber to a humidity (medium humidity) of 30 to 70% (RH). However, it has been found that with the system 100 having the above configuration, even if it can be adjusted to a humidity (high humidity) exceeding 70% (RH), it is difficult to accurately adjust the humidity to a lower range and maintain it.

Herein, the object of the present invention is to provide a microneedle preparation system. The manufacturing system and the air conditioning method are capable of adjusting the air environment in the coating chamber where the microneedle is coated with the drug to a humidity of 30 to 70% (RH).

In order to achieve the above object, the present invention provides a system for producing a microneedle preparation for applying a coating liquid containing a pharmaceutical agent to a microneedle to manufacture a microneedle preparation, and adjusting a microneedle preparation for an air environment in a coating chamber. The system includes: an air compressor, a humidity-permeable membrane type humidity adjusting device for adjusting the humidity of the air supplied by the air compressor, and the air and the moisture as a humidity adjusting source are separated by the moisture permeable membrane, And a pressure adjusting device that adjusts the pressure of the air supplied by the air compressor, and an air filter that sterilizes the air supplied into the coating chamber.

The system for producing a microneedle preparation having such a configuration is used in an environment having a temperature within a specific range, and the pressure of the air flowing through the flow path in the moisture permeable membrane type humidity control device can be controlled at 30~. Any humidity in the range of 70% (RH), and the sterilized air is stably supplied into the coating chamber.

The moisture permeable film can be formed into a hollow fibril. The moisture permeable film is formed into a hollow fibril shape, and humidity adjustment can be performed more efficiently.

The system for producing a microneedle preparation is preferably a first control means including a humidity detector and a signal for controlling the pressure adjusting means based on a signal corresponding to the humidity detected by the humidity detector. Further, the microneedle preparation system may be provided with a temperature detector and a second control means for controlling the pressure adjustment means based on a signal corresponding to the temperature detected by the temperature detector. By providing the first control means and/or the second control means in this manner, The pressure regulating device can be operated at any time in response to the temperature and humidity in the coating chamber, and the temperature and humidity in the coating chamber can be controlled more efficiently and reliably.

The system for manufacturing microneedle preparations can also be adjusted by air pressure A compressed air temperature regulating device that reduces the temperature of the air supplied by the machine. When the temperature of the environment in which the system is configured varies, and the air supplied to the system is not within the desired range due to the air compressor, the system can be fed into the coating chamber by providing a compressed air temperature adjusting device. The air is regulated to an arbitrary temperature, and the humidity can be controlled more accurately.

The microneedle preparation system can also be equipped with a humidity detector and Preferably, the third control means controls the compressed air temperature adjusting means based on a signal corresponding to the humidity detected by the humidity detector. Further, the system for producing a microneedle preparation may further include a temperature detector and a fourth control means for controlling the compressed air temperature adjusting means based on a signal corresponding to the temperature detected by the temperature detector. By providing the third control means and/or the fourth control means in this manner, the compressed air temperature adjusting device can be operated at any time in accordance with the temperature and humidity in the coating chamber, and the temperature in the coating chamber can be controlled more efficiently and reliably. humidity.

The humidity regulator has a water supply device for supplying moisture Suitable for. With such a configuration, the humidity control device can easily supply the moisture for adjusting the humidity in the system.

Further, the moisture supplier is preferably a constant temperature water tank. By being constant Since the warm water tank is used as a water supply device, the moisture of the moisture supplier can be easily maintained at a constant temperature, so that the temperature and humidity can be controlled with high precision.

Moreover, the moisture supplier is a person capable of adjusting the water temperature, that is, In the temperature range having the amplitude, it can be effective to adjust to any temperature. By having such a function, the moisture supplier can maintain the moisture of the moisture supplier at any constant temperature in a wide range.

The microneedle preparation system can also be equipped with a humidity detector, And a fifth control means for controlling the water temperature of the moisture supplier based on a signal corresponding to the humidity detected by the humidity detector. Further, the system for producing a microneedle preparation may further include a temperature detector and a sixth control means for controlling the water temperature control of the moisture supplier based on a signal corresponding to the temperature detected by the temperature detector. By providing the fifth control means and/or the sixth control means in this manner, the water temperature of the water supply device can be manipulated at any time in accordance with the temperature and humidity in the coating chamber, and the coating chamber can be controlled more effectively and more reliably. Temperature and humidity.

By other aspects of the invention, an air conditioner is provided The method for applying a coating liquid containing a drug to a microneedle to manufacture a microneedle preparation, and an air conditioning method for adjusting an air environment in a coating chamber, comprising: the air and the moisture as a humidity adjustment source a moisture permeable membrane type humidity adjusting device which is separated by a moisture permeable membrane to adjust the humidity of the air supplied to the coating chamber, and a step of adjusting the pressure of the air supplied to the coating chamber by the pressure adjusting means And the step of sterilizing the air by means of an air filter, and introducing the humidity-conditioned and sterilized air into the coating The steps in the chamber.

With such an air conditioning method, by using the temperature as a specific The air in the enclosure is supplied to the humidity control device, and the sterilized air having a temperature within a desired range and controlled to any humidity in the range of 30 to 70% (RH) can be stably supplied into the coating chamber.

According to the system for producing a microneedle preparation of the present invention or the air conditioning method, it is possible to stably supply the temperature in a desired range and any humidity in a range of 30 to 70% (RH) to the coating chamber in a sterile state. indoor. Thereby, the temperature and humidity of the coating chamber can be maintained within a desired range without being affected by fluctuations in the temperature and humidity inside and outside the coating chamber, and the fluctuation of the physical properties of the coating liquid in the coating chamber can be suppressed. Therefore, according to the system for producing a microneedle preparation of the present invention or the air conditioning method, when a coating liquid containing a drug is applied to a microneedle in an adjusted air atmosphere, a microneedle preparation coated with a certain amount of a drug can be stably produced.

10‧‧‧Air compressor

12‧‧‧Compressed air temperature regulator

14‧‧‧Air volume adjustment device

16‧‧‧Air filter

18‧‧‧Humidity control device

20‧‧‧ Coating chamber

21‧‧‧ openings

22‧‧‧Water supply

23‧‧‧Translucent membrane

24‧‧ ‧ wet film device

26‧‧‧ Temperature and Humidity Detector (Temperature Detector and Humidity Detector)

28‧‧‧Control device (1st to 6th control means)

30‧‧‧ Pressure regulating device

40‧‧‧Microneedle preparation

42‧‧‧Substrate

44‧‧‧microneedle

46‧‧‧coating layer

50‧‧‧ Coating solution

52‧‧‧Barrier board

54‧‧‧Scrape

56‧‧‧ openings

100,200‧‧‧Microneedle preparation system

L‧‧‧Air supply line

Fig. 1 is a block flow chart showing an embodiment of a system for producing a microneedle preparation.

Fig. 2 is a block flow chart showing an embodiment of a system for producing a microneedle preparation.

[Fig. 3] shows one of humidity adjusting devices in a system for manufacturing a microneedle preparation A cross-sectional view of a mode of the embodiment.

Fig. 4 is a perspective view showing an example of a microneedle preparation.

Fig. 5 is a cross-sectional view taken along the line V-V of the microneedle preparation of Fig. 4.

Fig. 6 (a) to (c) are schematic views showing an example of a method for producing a microneedle preparation.

[Fig. 7] (a) to (c) are graphs showing changes in humidity in the coating chamber.

Fig. 8 is a graph showing the content of a drug applied to a microneedle.

Fig. 9 is a schematic perspective view showing a coating chamber for an air volume adjustment test.

Fig. 10 (a) is a graph showing a temperature change in a coating chamber, and (b) is a graph showing a change in humidity in a coating chamber.

Fig. 11 (a) is a graph showing a change in temperature in a coating chamber, and (b) is a graph showing a change in humidity in a coating chamber.

[Formation of the Invention]

Hereinafter, preferred embodiments of the microneedle preparation system and the air conditioning method of the present invention will be described with reference to the drawings. In the drawings, the same reference numerals are given to the same or parts, and the detailed description is omitted.

The system for producing a microneedle preparation according to the present embodiment (hereinafter sometimes referred to simply as "system") is an air environment suitable for applying a coating liquid containing a drug to a microneedle to produce micro The operation of the needle preparation. In this specification, humidity means relative humidity.

2 is a view showing a system for producing a microneedle preparation of the present invention A block flow diagram of one embodiment. The system for manufacturing the microneedle preparation system 200 is configured such that the air compressor 10, the compressed air temperature adjusting device 12, the pressure adjusting device 30, the humidity adjusting device 18, the air volume adjusting device 14, and the air filter 16 respectively separate the air supply in this order. Line L is connected. The end point of the air supply line L is connected to the coating chamber 20 in which the microneedles are disposed and the application of the drug is performed.

Next, each configuration of the system for producing a microneedle preparation according to the present embodiment will be described.

The air compressor 10 in the system for producing a microneedle preparation according to the present embodiment is not particularly limited as long as it can generate a desired air velocity (flow velocity). Therefore, the air compressor 10 is not limited to the compressor defined by JIS (B 0132:2005), and a blower having a relatively low compression can be used. The air volume supplied from the air compressor 10 to the air in the system 200 is preferably from 10 to 250 L/min, more preferably from 20 to 100 L/min. Moreover, the air volume can also be 0.3~10L/min. The amount of air supplied to the air can be calculated as the amount of wind in each volume of the coating chamber 20. The air volume supplied to the coating chamber 20 in 1 L per volume is preferably 28 to 696 L/min, more preferably 56 to 278 L/min. Further, the amount of air supplied to the coating chamber 20 in 1 L per volume may be 1 to 28 L/min. Further, as the air supplied to the system 200 by the air compressor 10, although the air existing outside the system can be used, the group of the coating liquid applied to the microneedles is required. It can also be mixed with any gas.

The microneedle preparation manufacturing system 200 according to the embodiment The compressed air temperature adjusting device 12 can adjust the temperature of the air supplied from the outside to the system 200 by the air compressor 10 to an arbitrary temperature. Therefore, even if the temperature of the outside air of the system 200 is changed in the future and in the daytime, by providing the compressed air temperature adjusting device 12, the temperature of the air flowing through the system 200 can be maintained at a desired level without the external environment. Within the scope. In the compressed air temperature adjusting device 12, the temperature of the air injected into the compressed air temperature adjusting device 12 is preferably in the range of about 5 to 40 °C. The temperature of the air sent to the downstream air supply line L by the compressed air temperature adjusting device 12 can be arbitrarily set depending on the composition of the coating liquid to be used, but it is set at around room temperature from the viewpoint of efficiency of temperature adjustment. Good, set at 20~30 °C is better. Further, it is preferable to use the compressed air temperature adjusting device 12 capable of controlling the temperature of the exhaust air to be ±0.5 ° C or less. As the compressed air temperature adjusting device 12, any temperature control method, cooling method, or the like can be used as long as the temperature of the compressed air can be accurately controlled.

The humidity adjusting device 18 in the microneedle preparation system 200 according to the present embodiment can be used by combining the above-described compressed air temperature adjusting device 12, and the air flowing through the system 200 can be adjusted to a desired humidity. In particular, the humidity in the range of 30 to 70% (RH) is maintained. The humidity control device 18 is of a moisture permeable film type and has a moisture permeable film device 24 including a moisture permeable film formed into a hollow fiber shape. So wet The membrane type humidity controller 18 may further include a moisture supplier 22 that supplies moisture. As the moisture permeable film, for example, an ion exchange resin can be used to form a hollow fibril. The moisture permeable film has a property of allowing water vapor to pass therethrough without passing water of the liquid.

The water supplier 22 is used to control a certain water temperature. The constant temperature water tank is effective. Moreover, the constant temperature water tank can be adjusted to have a temperature range of amplitude, and can be adjusted to any temperature with high precision. The water used in the moisture supplier 22 is preferably pure water in order to ensure its sterility. The moisture supplied to the moisture permeable membrane device 24 by the moisture supplier 22 is interposed between the moisture permeable membrane and supplied to the system 200 as vaporized vapor.

As the moisture permeable membrane device 24, from the viewpoint of efficiency, It is preferable to use a hollow fiber module in which a moisture-permeable film formed into a hollow fiber shape is fixed in a plurality of bundles. When the hollow fiber module is used, the hollow fiber module is connected to the air supply line L of the system 200 so that the air flowing through the system 200 can pass through the inside of the hollow fiber-like moisture permeable film. Further, the outside of the hollow fiber-shaped moisture permeable membrane is configured such that the water supply device 22, preferably water which is controlled by the constant temperature water tank to control the water temperature, is circulated, and is often circulated in the hollow fiber-like moisture permeable membrane and the water supply. Preferably, the devices 22 are between each other. When a hollow fiber-like moisture permeable membrane is interposed between a certain temperature of a certain temperature, a gas of a specific range of humidity is derived by the hollow fiber module. Therefore, the air whose temperature is adjusted by the compressed air temperature adjusting device 12 is introduced into the hollow fiber module, and the pure water from a certain temperature of the constant temperature water tank can pass through the hollow fiber module to obtain the hollow fiber mold. Group The air has a desired range of humidity and flows downstream. Further, by controlling the water temperature of the water supplier 22 such as the constant temperature water tank, the humidity can be controlled with high precision. That is, by raising the temperature of the water to a certain temperature, the air flowing through the system 200 can be humidified to a humidity corresponding to the temperature, and conversely, by lowering the temperature of the water to a certain temperature, it can be circulated. The air in the system 200 is dehumidified to a humidity corresponding to its temperature. Further, when the moisture permeable membrane device 24 having the hollow fiber module is used, since the filter function is provided in the hollow fiber module, it is possible that the microorganisms contained in the water in the moisture supplier 22 can be made by the hollow fiber mold. The group is captured and can be prevented from being mixed into the air flowing through the system 200.

The microneedle preparation manufacturing system 200 according to the embodiment The medium pressure adjusting device 30 is a person capable of adjusting the pressure inside the hollow fibrillar moisture permeable membrane of the moisture permeable membrane device 24. The pressure regulating device 30 is disposed downstream of the compressed air temperature adjusting device 12 and upstream of the moisture permeable membrane device 24. In the system 200, since the moisture permeable membrane of the moisture permeable membrane device 24 is formed into a hollow fibril shape, the pressure of the air introduced into the moisture permeable membrane device 24 can be adjusted by the pressure adjusting device 30, and the moisture permeable can be adjusted. The humidity of the air derived by the membrane device 24 is particularly suitable for adjusting the humidity in the coating chamber to a humidity of about 30 to 70% (RH). As the pressure adjusting device 30, as long as the pressure can be accurately adjusted, for example, a diaphragm type can be used. As the pressure adjusting device 30, a person who can adjust the pressure in the range of 0.02 to 1.0 MPa can be used.

The air filter 16 in the system for producing a microneedle preparation according to the present embodiment is not limited to any one as long as it can capture microorganisms such as bacteria and fungi contained in the air and is sterilized. By using such an air filter 16, it is possible to remove not only microorganisms but also dust in the air. The pore diameter of the filter 16 is preferably 0.2 μm or less from the viewpoint of sterilization efficiency. In addition, for example, a filter having a dust removing effect such as a HEPA (High Efficiency Particulate Air) filter or an air filter having a sterilization effect can be used, and two or more air filters can be used. In the system 200 according to the present embodiment, since the air supplied from the air compressor 10 flows uninterruptedly to the opening 21 of the coating chamber 20, the air filter 16 is provided in the system 200, so that the coating chamber can be more reliably The chamber 20 remains sterile. Although the air filter 16 is provided on the downstream side of the air volume adjusting device 14, it can be disposed at any position from the air compressor 10 in the present system 200 to the air supply line L on the downstream side. Among them, it is preferable to be disposed downstream of the humidity adjusting device 18 in view of the relationship between the arrangement layout and the pressure control efficiency.

The microneedle preparation manufacturing system 200 according to the embodiment The air supply line L in the middle may be any form as long as it has no air leakage. In order to more reliably suppress the effect of the temperature adjustment caused by the air temperature adjusting device 12, and to more stably maintain the air environment in the coating chamber 20 at a desired temperature, the air supply line L is preferably a heat blocking effect. In order to make the air supply line L have a heat-blocking effect, the heat-insulating material may be disposed to cover the periphery of the air supply line L, or the material of the air supply line L may be used as a material having a heat-blocking effect.

The humidity and humidity adjustment device 18 is temperature and humidity within a specific range. The air which is taken out and sterilized by the air filter 16 is internally sent to the coating chamber 20 for applying the coating liquid containing the drug to the microneedles to manufacture the microneedle preparation. The coating chamber 20 has an opening 21 at a portion of its wall surface. This opening 21 functions not only as an exhaust port for discharging the air supplied from the system 200 but also as a carry-in port for the microneedle preparation to which the coating liquid is applied. The opening 21, when the coating chamber 20 is, for example, a box type, may be disposed on the upper surface of the coating chamber 20 or on the side or below. In order to adequately satisfy the desired air environment within the coating chamber 20, it is preferred that the opening 21 is sufficiently separated from the portion of the system 200. The amount of air blown into the coating chamber 20 is preferably maintained at a high amount. By sufficiently maintaining the air volume at a high amount, the inside of the coating chamber 20 can be maintained at a positive pressure with respect to the outside of the system 200, and external air can be prevented from flowing into the coating chamber 20 from the opening 21. Therefore, it is possible to maintain the inside of the coating chamber 20 at a desired temperature and humidity, and it is possible to prevent the fungus from entering the inside of the coating chamber 20 from the opening 21.

In the interior of the coating chamber 20, in order to grasp the coating chamber 20 The temperature and humidity of the air inside is preferably set to a temperature and humidity detector (temperature detector and humidity detector) 26. This is because it is possible to constantly control whether the air supplied from the system 200 into the coating chamber 20 is maintained at a desired temperature and humidity, so that the pressure adjusting device 30 and the compressed air temperature can be sequentially operated in accordance with the temperature and humidity in the coating chamber 20. The adjusting device 12 and the humidity adjusting device 18 further strictly control the temperature and humidity of the air in the coating chamber 20. Moreover, a system can also be provided, which will correspond to the temperature and humidity detector 26 The detected temperature and humidity signal in the coating chamber 20 is sent to the control device (the first control means for controlling the pressure adjusting device 30 and/or the second control means, and the third control means for controlling the compressed air temperature adjusting means 12 and / or the fourth control means and the fifth control means and/or the sixth control means 28 for controlling the water temperature of the water supplier 22, based on the signal, the control means 28 operates the pressure adjusting means 30 and the compressed air temperature adjusting means 12 or a system of moisture supply 22 in humidity conditioning device 18, that is, a feedback system. Specifically, for example, a feedback system can be provided which detects that the set pressure of the pressure adjusting device 30 is lowered if the humidity in the coating chamber 20 is lowered, and conversely, if the coating chamber 20 is detected. When the humidity rises, the set pressure of the pressure adjusting device 30 is raised. Similarly, for example, a feedback system can be provided which detects the heating mechanism of the moisture supplier 22 after detecting that the humidity in the coating chamber 20 is low, and conversely, if the humidity in the coating chamber 20 is detected to rise, Then, the cooling mechanism of the moisture supplier 22 is operated. Further, for example, if it is detected that the temperature in the coating chamber 20 is lower than a specific lower limit value, the heating of the heating mechanism of the compressed air temperature adjusting device 12 is promoted, or the cooling of the cooling mechanism is suppressed, and conversely, When it is detected that the temperature in the coating chamber 20 is higher than a certain upper limit, the heating of the heating mechanism of the compressed air temperature adjusting device 12 is suppressed, or the cooling feedback system of the cooling mechanism is promoted. By providing such a feedback system, temperature and humidity control within the coating chamber 20 can be performed more efficiently and reliably.

When the microneedle preparation manufacturing system 200 having the above configuration is operated, first, air is sucked from the outside through the air compressor 10. Into, and supplied to the system 200. The air supplied by the air compressor 10 is injected into the compressed air temperature adjusting device 12 through the air supply line L, and is adjusted to a specific temperature. The air adjusted to a specific temperature by the compressed air temperature adjusting device 12 is injected into the pressure adjusting device 30 through the air supply line L, and is adjusted to a specific pressure. The air whose pressure is regulated by the pressure adjusting device 30 passes through the air supply line L and is injected into the humidity adjusting device 18 to be adjusted to a specific humidity. The air whose humidity is adjusted by the humidity adjusting device 18 is sterilized by the air filter 16 after the air volume adjustment is necessary. The air whose temperature and humidity are adjusted and sterilized is supplied to the coating chamber 20 through the air supply line L. The air previously present in the coating chamber 20 is discharged from the opening 21 provided in a portion of the wall surface constituting the coating chamber 20, and the inside of the coating chamber 20 is filled with the desired temperature and humidity and is sterilized. air. The air supplied to the coating chamber 20 by the present system 200 is discharged from the opening 21 at any time. The air that has flowed through the system 200 flows in the same direction toward the opening 21 in a state of having a certain degree of wind speed due to the wind power supplied from the air compressor 10. Therefore, air does not remain inside the system 200, and even if bacteria are present inside the system 200, the reproduction is suppressed.

In the coating chamber 20, it can be prepared to be applied to the microneedles in advance. A coating solution containing a drug. During the coating operation, as described above, since the coating chamber 20 is often in a specific range of temperature and humidity and in an aseptic environment, the gasification reaction of water contained in the coating liquid and the moisture in the air are caused. The liquefaction reaction is controlled and can inhibit the change of the physical properties of the coating liquid. Chemical. Therefore, unevenness in the amount of the drug applied to the microneedles can be suppressed, and the microneedle preparation can be stably produced in a sterile environment. The CV (coefficient of variation) value of the left and right sides of the amount of the drug applied to the microneedles is preferably 10% or less, more preferably 5% or less. The CV value means the value obtained by dividing the standard deviation by the average value and expressed as a percentage.

Although the amount of air from the air compressor 10 (flow) The amount can be adjusted by the function of the air compressor 10 itself. However, since the air volume adjusting device 14 is connected to the downstream side of the air compressor 10, it is possible to adjust the air volume of the air flowing through the system 200 with high precision. . When the system 200 includes the air volume adjusting device 14, the amount of the air applied to the microneedles can be controlled by slightly adjusting the amount of air flowing through the system 200. Further, when the air volume is a certain amount or more, for example, 0.5 L/min or more, the temperature and humidity distribution in the coating chamber can be more uniformized. The air volume adjusting device 14 is preferably disposed downstream of the humidity adjusting device 18 from the viewpoint of setting the layout and the efficiency of the pressure control.

In the above embodiment, the environment of the system 200 is set. Although the temperature is described as a changer, when the system 200 is used in a space where the temperature of the entire environment is controlled, when the air supplied from the air compressor 10 has been maintained at a specific temperature, it is in the middle of construction. It is also possible not to have the compressed air temperature adjustment device 12.

Moreover, the humidity adjusting device 18 has a hollow The moisture permeable membrane device 24 of the fibril-like moisture permeable membrane is described, but the moisture permeable membrane is not limited to the hollow filament shape, and any shape may be used. The humidity adjusting device 18 shown in Fig. 3 has a moisture permeable film disposed on the partition type twenty three. The moisture permeable film 23 in Fig. 3 separates the air supplied to the system 200 by the air compressor 10 from the moisture as a humidity control source. The moisture permeates the moisture permeable membrane 23 and is supplied as water vapor to the air flowing through the flow path of the system 200.

The pressure regulating device 30 in Fig. 3 is connected to the humidity adjustment The outside of the upstream side of the device 18 adjusts the pressure of the air introduced into the humidity control device 18. Further, the pressure adjusting device 30 may be disposed inside the humidity adjusting device 18 and adjust the pressure of the air introduced into the humidity adjusting device 18.

Using the system for manufacturing a microneedle preparation in the above configuration, the needle An outline of the method for producing a microneedle preparation is described. Fig. 4 is a perspective view showing an example of a microneedle preparation produced by using the system according to the embodiment. The microneedle preparation 40 shown in FIG. 4 includes a substrate 42 and a plurality of microneedles 44 disposed on the substrate 42 in a bipolar shape, and a coating layer 46 formed on the microneedles 44. The coating layer 46 is applied by using the system for producing a microneedle preparation according to the present embodiment, and at least a part of the volatile component is preferably removed.

The substrate 42 is a base for supporting the microneedles 44. The area of the substrate 42 is preferably 0.5 to 10 cm ² , more preferably 1 to 5 cm ² , still more preferably 1 to 3 cm ² . A substrate of a desired size can also be formed by combining a plurality of the substrates 42.

The microneedles 44 have a minute structure and have a height (length) of preferably 50 to 600 μm. Here, by setting the length of the microneedles 44 to 50 μm or more, the administration of the drug contained in the coating liquid can be reliably performed. Moreover, by setting the length of the microneedles 44 to 600 μm or less, it is possible to avoid contact of the microneedles with the nerves, and to surely reduce the possibility of pain while avoiding the possibility of bleeding. Further, when the length of the microneedles 44 is 500 μm or less, the amount of the drug to be injected into the skin can be efficiently administered, and the base film can be administered without being perforated. The length of the microneedles 44 is particularly preferably 300 to 500 μm.

Here, the microneedle 44 means a convex structure, and broadly means a needle shape or a structure including a needle shape. However, the microneedle is not limited to a needle shape having a sharp front end, and may have a non-sharp shape at the front end. When the microneedle 44 has a conical structure, the diameter of the base is preferably about 50 to 200 μm . In the present embodiment, the microneedles 44 have a conical shape, but may be a polygonal pyramid such as a quadrangular pyramid or a microneedle of another shape.

The microneedles 44 are typically arranged to be separated at intervals of a density of about 1 to 10 per 1 mm in the course of the needle. In general, the adjacent courses are substantially separated from each other by an equal distance with respect to the space of the needles in the course, and have a needle density of 100 to 10,000 per 1 cm ² . If it has a needle density of 100 or more, it can pass through the skin efficiently. On the other hand, with a needle density of more than 10,000, it is difficult to maintain the strength of the microneedles 44. The density of the microneedles 44 is preferably 200 to 5,000, more preferably 300 to 2,000, and particularly preferably 400 to 850.

As the material of the substrate 42 or the microneedles 44, although Antimony, cerium oxide, porcelain, metal (stainless steel, titanium, nickel, molybdenum, chromium, cobalt, etc.) and synthetic or natural resin materials, etc., but considering the antigenicity of the microneedles and the unit price of the material, polylactic acid, polyethylene Lactide, polylactic acid-co-polyethylene Biodegradable polymer such as ester, amylopectin, caprolactone, polyurethane, polyanhydride or polycarbonate of non-decomposable polymer, polymethacrylic acid, ethylene vinyl acetate, polytetrafluoroethylene, polyacetal, etc. Synthetic or natural resin materials are especially good. Further, hyaluronic acid, sodium hyaluronate, amylopectin, hexose, dextrin or chondroitin sulfate are also suitable.

As a method of manufacturing the substrate 42 or the microneedle 44, there is a use Wet etching or dry etching of a substrate, precision machining using metal or resin (electric discharge machining, laser machining, cutting, hot press molding, injection molding, etc.), mechanical cutting, and the like. The substrate 42 and the microneedles 44 are integrally molded by this processing method. As a method of making the microneedles 44 hollow, there is a method of performing the secondary processing by laser or the like after the microneedles 44 are produced.

In the microneedle preparation 40, although the microneedle 44 is coated Layer 46, but coating layer 46 is preferably formed by coating a coating liquid. As the coating method, spray coating, dip coating, or the like is exemplified, and dip coating is preferred. Further, in FIG. 4, the coating layer 46 is formed on all of the microneedles 44, but the coating layer 46 may be formed only in a part of the plurality of microneedles 44 present. In FIG. 4, although the coating layer 46 is formed only at the front end portion of the microneedles 44, it may be formed so as to be coated on the entire microneedles 44. Further, the coating layer 46 may be formed on the substrate 42.

Figure 5 is a cross-sectional view taken along line V-V of Figure 4; As shown in Figure 5, The microneedle preparation 40 is provided with a substrate 42, a microneedle 44 provided on the substrate 42, and a coating layer 46 provided on the microneedle 44. The coating layer 46 attached to the microneedles is a drug-containing one, and can be produced, for example, by the above steps. Made.

Figures 6(a), (b) and (c) show the microneedle preparation 40 An example of a manufacturing method. This method is called the dipping method. In this method, first, as shown in FIG. 6(a), the coating liquid 50 is scraped on the barrier sheet 52 in the direction of the arrow A by the spatula 54. Thereby, the coating liquid 50 is filled in the opening 56. Next, as shown in FIG. 6(b), the microneedles 44 are inserted into the opening portion 56 of the barrier panel 52. Thereafter, as shown in FIG. 6(c), the microneedles 44 are pulled out from the opening 56 of the barrier panel 52. Thereby, the coating liquid 50 is attached to the microneedles 44. Further, the coating liquid 50 may be attached to the substrate 42.

Although it is carried out in the coating chamber by Fig. 6(a), (b) and (c), the microneedle preparation is manufactured, but as a condition at this time, the coating chamber is made into a sterilized air having a controlled temperature and humidity by using the system according to the embodiment. surroundings. Specifically, each device in the system is activated, and the air supplied by the air compressor is adjusted to a desired environment and then blown into the coating chamber. By returning the temperature and humidity measurement result in the coating chamber to the constant temperature water tank or the like, it is possible to stably maintain the air environment of the desired temperature and humidity. By coating in the air atmosphere thus obtained, it is possible to stably apply a coating liquid having a certain chemical content to the microneedles.

After coating as described above, by air drying, vacuum drying, Or a combination of these, a method of removing the volatile component of the coating liquid 50 on the microneedles 44. Thereby, the coating layer 46 is firmly adhered to the microneedles 44 and becomes a typical vitreous or solid to manufacture a microneedle preparation. 40. The water content of the coating layer 46 is usually 55 mass% or less, more preferably 30 mass% or less, and further 10 mass% or less, based on the total amount of the coating layer 46. According to the above method, it is possible to prevent the liquid of the applied coating liquid 50 from dripping. The liquid dripping means that the coating liquid is dripped from the needle, and in Fig. 6(c), the H portion is elongated.

The height H of the coating layer 46 attached to the microneedles 44 is adjusted by a gap (slit) C as shown in Fig. 6(b). This gap C is defined as the distance from the base of the microneedle 44 to the surface of the barrier plate 52 (independent of the thickness of the substrate 42) and is set in accordance with the tensile force of the barrier plate 52 and the length of the microneedle 44. The distance of the gap C is preferably in the range of 0 to 500 μm . When the distance of the gap C is 0, it means that the coating liquid 50 is applied to the entirety of the microneedles 44. The height H of the coating liquid 50 adhering to the microneedles 44 varies depending on the height of the microneedles 44, but can be 0 to 500 μm , usually 10 to 500 μm , preferably about 30 to 300 μm . Especially good is about 40~250 μm . In order to effectively use the agent in the coating liquid 50, a part of the microneedle is concentrated, that is, the tip end portion of the needle is preferable, and from the viewpoint of skin irritation and drug migration rate to the skin, it is also present at the front end to 200 μ m is preferred. The coating liquid 50 can dissolve the polymer compound in an aqueous solution, for example, and can form the coating layer 46 in one of the microneedles with high viscosity. The coating liquid 50 held on the microneedles 44 in such a manner is simultaneously inserted into the skin while the microneedles 44 are punctured to the skin.

The coating layer 46 adhered to the microneedles 44 preferably has a thickness of less than 50 μm after drying, more preferably less than 40 μm , still more preferably 1 to 30 μm . Generally, the thickness of the coating layer 46 attached to the microneedles is the average thickness measured across the surface of the microneedles 44 after drying. The thickness of the coating layer 46 adhering to the microneedles 44 is increased by the plurality of coatings applied to the coating liquid 50, that is, after the coating liquid 50 is attached, it can be increased by repeating the adhesion step.

As the agent contained in the coating liquid 50, for example, there is a victory. The polymer compound such as a peptide, a protein, a DNA, or an RNA is not particularly limited, and may have a molecular weight of about 1,000, that is, a vaccine, a low molecular peptide, a sugar, or a nucleic acid. As physiologically active substances, for example, naltrexone, cetrorelix acetate, statin, nafarelin acetate, prostaglandin A1, apredrainin, α-interferon, for multiple sclerosis Β-interferon, erythropoietin, follicle stimulating hormone β, follicle stimulating α, G-CSF, GM-CSF, human villus gonad stimulation hormone, leuntizing hormone, sputum Calcitonin, glycoside, GNRH anti-antagonism, insulin, human growth hormone, Whirlpool blood, heparin, low molecular weight heparin, growth hormone, incretin, GLP-1 inducer, and the like. Further, examples of vaccines include Japanese encephalitis vaccine, rotavirus vaccine, Alzheimer's disease vaccine, arteriosclerosis vaccine, cancer vaccine, nicotine vaccine, diphtheria vaccine, tetanus vaccine, pertussis vaccine, and Lyme disease vaccine. , rabies vaccine, pneumococcal vaccine, yellow fever vaccine, cholera vaccine, vaccinia vaccine, tuberculosis vaccine, German measles vaccine, measles vaccine, mumps vaccine, botulinum vaccine, herpes virus vaccine, other DNA vaccine, hepatitis B Vaccines, etc.

Others, such as hypnosis. Sedative Luo, limazabine hydrochloride, phenobarbital, isobarbital, etc.) Inflammatory analgesic (butorphanol tartrate, pyridoxal citrate, acetaminophen, mefenamic acid, sodium diclofenac, aspirin, aclofenac, docopyrene, flupeptone Fen, Naproxine, Piloca, New Analgesic, Acacia, Salicylic Acid Glycol, Pelidine, Loxoprofen, etc.), Steroid Anti-Inflammatory (Cortisol, Dehydrocortic Alcohol, dexamethasone, shell cortisol, etc.), excited. Stimulant (methyl amphetamine hydrochloride, methylphenidate hydrochloride, etc.), psychotropic agent (imamine hydrochloride, diazapine, Lefu, hydrochloric acid, fluconate, paroxetine hydrochloride, bromine Hydrogen citalopram, Prozac Hydrochloride, Tridiazepine, Dopamine Antagonist, Clomipramine, Amitriptyline, Dexapride, Anmodipine, Maprotiline, Mise Lin, sputulin, sedative ingot, lofimamine, milnacipran, duloxetine, euphorbia, phenolic ketamine, methotrexate, diazapine, meipubamai, yi Tiazolam, etc., Hormone (espiratory, estriol, progesterone, acetate tacrosterone, metoprolol acetate, acetophenone, etc.), local anesthetic (lidocaine hydrochloride, hydrochloric acid) Novocaine, tetracaine hydrochloride, hydrochloric acid for bcacaine, prilocaine hydrochloride, etc.), urinary organ (Dadoo hydrochloride, tamsulosin hydrochloride, propiverine hydrochloride, etc.), bone relaxant (tizanidine hydrochloride, eperisone hydrochloride, piperazine mesylate, succinylcholine hydrochloride, etc.), genital organ (Litojun hydrochloride, tartaric acid) Epilepsy (dipropyl sodium acetate, clopropine, kappa nitrogen equal), autonomic nerve agent (methyl trimethylamine butyrate, neostigmine bromide, chloride, etc.), anti-Parkinson's disease Agent (pagsulfame methanesulfonate, bromopyridinium mesylate, chlorhexidine hydrochloride, amantadine hydrochloride, pirimidol hydrochloride, helicosine hydrochloride, lactose depressurization, dexcidopa, specific culture Liting, salt Acid dipnin, etc., diuretics (hydrofluoromethyl thiophene, foxima, etc.), respiratory enhancer (L. sylvestris hydrochloride, bismorpholamine, cloproxil hydrochloride, etc.), anti-piling headache agent (methane dihydrogen) Ergotamine, simeptan, ergotamine tartrate, flubenzate hydrochloride, serprestatin hydrochloride, etc., antihistamine (cortisol fumarate, diphenhydramine citrate, chlorpheniramine citrate) Anming, diphenylpyrazine hydrochloride, promethazine hydrochloride, etc., tracheal branch dilating agent (torbutrolol hydrochloride, kefuchuan hydrochloride, salbutamol sulfate, clenbuterol hydrochloride, hydrogen bromide phenoxide) Terbutaline Sulfate, Isoproterenol Sulfate, Formoterol Fumarate, etc., Cardiotonic (Isoproterenol Hydrochloride, Dopamine Hydrochloride, etc.), Coronary Vasodilator (Ditaxan Hydrochloride, Verapamil Hydrochloride) , nitric acid crown ingots, glyceryl trinitrate, nicorandil, etc.), peripheral vasodilator (Chuanzhi sugar ingot, benzyl imidazoline hydrochloride, etc.), non-smoking supplement (nicotine, etc.), circulatory organ (flunzetine hydrochloride) Net, ergipine hydrochloride, Niichuan to be flat, nisoldipine, philoxine, benzene sulfonate Nifludipine, nirvipine hydrochloride, benidipine hydrochloride, enalapril acephate, temocapril hydrochloride, alapril, midazolam hydrochloride, cilazapril, lisino Pu, captopril, trandolapril, tert-butylamine pellipril, attinol, fumarate bisulop, tartaric acid metoprolol, betaxolol hydrochloride, arolol hydrochloride, hydrochloric acid Celilol, Kallithopodol, carteolol hydrochloride, bevanolol hydrochloride, valsartan, candesartan tablets, losartan potassium, knitidine hydrochloride, etc., arrhythmia (Prodamine hydrochloride, dextrosine hydrochloride, nifecaine hydrochloride, mexiladine hydrochloride, Nadulu, Xindaning, etc.), anti-malignant ulcer agent (cyclophosphamide, fluorouracil, Youfu capsule, hydrochloric acid Procarbazine, ramustine, oleino dihydrochloride Ken, Fururijin, etc., anti-lipidemia agents (pravastatin, simvastatin, Benazol, cut bar, etc.), blood sugar lowering agents (Geliben, chlorpropamide, tolbutamide, Sodium gliproclidine, grebazole, dibutyl hydrazine hydrochloride, therapeutic agent for peptic ulcer (proglumide, cetrozine hydrochloride, spirofuranone, cimetidine, glucosinolate) Cholesterol (deoxyurin, acetaminophen, etc.), digestive tract exercise improver (Dopplidu, Hisapur, etc.), liver dysentery (tiopronin, etc.), anti-allergic agent (fumaric acid) Ketotifen, azelastine hydrochloride, etc., antiviral agent (acyclovir, etc.), sedative (sensitive saponin, difenidol hydrochloride, etc.), antibiotic (ceftidine, cefdinir, Cefpodoxime, cefotaxime, clarithromycin, erythromycin, methyl erythromycin, karna sulphate, cycloserine, tetracycline, benzylpenicillin potassium, propisillin, chlorthacillin sodium, amine Benzicillin capsules, ampicillin hydrochloride methyl amyl acetate, carbenicillin sodium, chloramphenicol, etc.), habitual poisoning agents (ammonium cyanide, etc.), appetite suppressants (chlorpheniramine, etc.), Chemotherapeutic agents (barium isonicotinate, ethionamide, pyridoxamine, etc.), blood coagulation accelerator (tidocapril hydrochloride, benzylacetone coumarin potassium), anti-senile dementia (phytosan) , Aiyixin hydrochloride, Taklin, betel nut, octopine, etc.), serotonin receptor antagonizing antiemetic agent (ondansetron hydrochloride, hydrochloric acid, you are strong, ramosetron hydrochloride, hydrochloric acid Zarsyn, etc.), gout therapeutics (colchicine, dipropyl sulfonamide, sulfinpyrazol, etc.), analgesics of anesthetic (phenentrene citrate, morphine sulfate, morphine hydrochloride, codeine phosphate, Cocaine hydrochloride, statin hydrochloride, etc.).

Moreover, these agents can also be used alone or in combination 2 The above-mentioned type may be a pharmaceutically acceptable salt, and of course, a drug in the form of either an inorganic salt or an organic salt. Further, the drug is basically included in the coating liquid, but the drug may not be contained in the coating liquid, and then supplied through a through hole formed in the substrate of the microneedle. The content of the (A) drug in the coating liquid is 0.1 to 80% by weight, preferably 1 to 70% by weight, particularly preferably 5 to 60% by weight.

The coating liquid may also contain a polymer different from the above agent Compound. Examples of the polymer compound include polyethylene oxide, polyhydroxymethyl cellulose, hydroxypropyl cellulose, polyhydroxypropylmethyl cellulose, polymethyl cellulose, hexasaccharide, and polyethylene glycol. Polyvinyl alcohol, polyvinyl pyrrolidone, amylopectin, sodium carboxymethylcellulose, chondroitin sulfate, hyaluronic acid, hexose, gum arabic, and the like.

Others, in the coating liquid, may also be added as necessary A propylene carbonate, a crotonone, a 1-menthol, a peppermint oil, a limonene, a diisopropyl adipate or the like as a dissolution aid or an absorption enhancer, or a methyl salicylate as a medicinal adjuvant , ethylene glycol salicylate, 1-menthol, thymol, peppermint oil, citric acid vanilla, red pepper extract, and the like.

Moreover, in the coating liquid, if necessary, it is also possible to add stability. Chemical agents, antioxidants, emulsifiers, surfactants, salts, and the like. The surfactant may also be any one of a nonionic active agent and an ionic active agent (cation, anion, amphoteric). In terms of safety, it is more desirable to be used in a conventional pharmaceutical base. Ionic active agent. More specifically, there are sugar alcohol fatty acid esters such as sucrose fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, and propylene glycol fatty acids. Ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene castor oil, polyoxyethylene hardened castor oil and the like.

Other known formulation supplements as long as they have a coating The solubility and viscosity characteristics required for the application of the liquid, and the harmful effects on the properties and physical properties of the coating layer after drying may not be adversely affected, and may be added to the coating liquid.

In the coating liquid, in order not to drip the liquid, it is necessary to have a certain The degree of stickiness must be about 100~100000 cps. The coating liquid preferably has a viscosity of 100 to 60,000 cps, and the viscosity is in this range, that is, the desired amount of the coating liquid can be applied at a time without depending on the material of the microneedles 44. Further, in general, the higher the viscosity, the higher the amount of the coating liquid to be applied is. When the viscosity is less than 600 cps, it is difficult to apply the minimum coating liquid to the microneedles 44. However, unexpectedly, when it is 45,000 cps or more, the amount of the agent in the coating layer 46 obtained by the conversion is reduced. From such a characteristic, the viscosity of the coating liquid is set to a viscosity of 45,000 cps or more. Since the content of the drug in the coating layer 46 corresponding to the use of the drug is not desired, and the economy is not good, the viscosity of the coating liquid is set at 600 to 45000 cps. Especially good.

[Examples]

Hereinafter, the present invention will be specifically described based on examples, but the present invention is not limited to the following examples.

(Example 1)

A system for manufacturing a microneedle preparation having an air compressor, a compressed air temperature adjusting device, a pressure adjusting device, a humidity adjusting device, an air volume adjusting device, and an air filter sequentially interposing a supply line is produced. As a humidity control device, a hollow fiber module and a constant temperature water tank are used in combination. Specifically, the inside of the hollow fibrillar membrane of the hollow fiber module is connected so that the gas flowing in the system passes through and is connected to the outside of the hollow fibrillar membrane of the hollow filament mold structure. The water of a certain temperature supplied by the constant temperature water tank contacts and circulates with the constant temperature water tank. A Teflon (registered trademark) line and a helium line are used in the air supply line connecting the devices, and a bubble nitrile synthetic rubber heat insulating material is disposed around the line as a heat resistant material. The details of each device used are as follows.

Air compressor: control pressure 0.6~0.8MPa, air volume 85L/min

Compressed air temperature regulator: electronic hot and cold, set discharge temperature 23 ° C

Air volume adjustment device: set air volume 30L/min

Air filter: made of polytetrafluoroethylene, with a hole diameter of 0.2 μ m and an effective area of 50 cm ²

Constant temperature water tank: circulating constant temperature water tank

Hollow fiber module: Built-in cylindrical module with hollow fiber filament made of fluorine-based ion exchange resin with inner diameter of 1mm, shape of 1.3mm and length of 300mm

Pressure regulator: feedback control precision regulator

The fabricated system was connected to the coating chamber via a polypropylene line. As the coating chamber, an acrylic chamber was used. The coating chamber is then covered with a canopy and the temperature and humidity within the canopy are managed by precision temperature and humidity elements. The constant temperature water tank was set to 23 ° C to start each device. The set pressure of the pressure adjusting device was set to 0.1 to 0.3 MPa, and the relative humidity (%) in the coating chamber was measured under the respective pressure conditions. The results are shown in Table 1. By controlling the pressure in the hollow fiber module with the pressure adjusting device, the coating chamber can be adjusted to any humidity below 70% (RH), and can also be adjusted to a humidity of about 30% (RH).

(Example 2)

The humidity maintenance test was carried out using the same system as in Example 1. The humidity in the coating chamber is adjusted by activating the various devices of the system and appropriately changing the set pressure of the pressure regulating device. The humidity in the coating chamber was measured over time. The results are shown in Fig. 7. In a humidity of about 30% (Fig. 7(a)), about 50% (Fig. 7(b)), and about 70% (Fig. 7(c)), the humidity in the coating chamber can be maintained over a long period of time. for sure.

(Example 3)

The coating test of the microneedle device was carried out by adjusting the temperature and humidity into a coating chamber of 23 ° C and 60% (RH) in the same manner as in Example 1. The specific method of the coating test is as follows.

(Microneedles)

Material: polylactic acid, height: 500μm, density: 625/cm ² , preparation area of microneedle device: 1cm ² /patch

(coating liquid)

The coating liquid was obtained by mixing 2% by mass of sodium benzoate, 38% by mass of hexose carbon 40, 48% by mass of glycerin, and 12% by mass of purified water.

The application of the coating liquid for the microneedles is carried out by the method shown in Fig. 6 (a) to (c) above. The resulting coating liquid was scraped off with a spatula and filled in the opening of the metal barrier plate on a metal barrier plate (thickness 75 μm , opening diameter 250 μm , pitch 400 μm ) disposed in the coating chamber. . The coating liquid is applied to the microneedles by inserting the microneedles into the filled opening and extracting them. The coated microneedles were air-dried and stored at room temperature. After being applied to 100 microneedle devices, one was taken out from every 10, and the amount of sodium benzoate applied was quantified. As a method of quantifying sodium benzoate, the drug on the microneedle after air drying was extracted with 1 ml of water, and the concentration of sodium benzoate in the obtained extract was measured by HPLC. The content on each of the microneedle preparations was calculated from the obtained measured values. The results are shown in Fig. 8. The content of the sample drug on the dried microneedle was very small between the methods, and the average content of sodium benzoate was 1.8 μg, the standard deviation was 0.1 μg, and the CV value was 7.0%.

(Example 4)

The air volume adjustment test was carried out using the same system as in Example 1 and the coating chamber shown in Fig. 9. The size of the coating chamber is as follows.

Height 35mm, width 50mm, length 205mm, volume about 0.359L

Exhaust port (opening) 21: rectangular, 25mm × 30mm

Air supply port connected to the air supply line L: round, 16mm in diameter

Each device of the system is started, and the air volume is set to the values shown in Table 2 by the air volume adjusting device, and the temperature of the constant temperature water tank, the circulating water volume, and the compressed air temperature are appropriately adjusted as necessary. In the coating chamber, a total of five measurement positions p at the center and four corners are provided, and each is set to a height of one-half of the height of the coating chamber. The humidity was measured at each measurement position p, and the average humidity, standard deviation (SD), and CV value at five points were obtained. The results are shown in Table 2. Although the air volume can adjust the humidity arbitrarily at any value, the humidity in the coating chamber can be more uniformly adjusted when the air volume is more than a certain amount.

(Comparative Example 1)

A system for manufacturing a microneedle preparation having an air compressor, a compressed air temperature adjusting device, an air volume adjusting device, an air filter, and a humidity adjusting device is sequentially manufactured. In the respective devices, the same as in the first embodiment, the same as in the first embodiment. The system for producing a microneedle preparation produced in the same manner as in Example 1 was connected to an acrylic coating chamber via a polypropylene line. The coating chamber is then covered with a canopy and the temperature and humidity within the canopy are managed by precision temperature and humidity elements. The devices are activated and the coating chamber is filled with air having a regulated temperature and humidity.

The temperature and humidity in the coating chamber were measured over time. The results are shown in Figures 10(a) and (b). In the system of Comparative Example 1, although the temperature and humidity in the coating chamber can be adjusted to a desired range, even if the temperature of the water circulating in the hollow fiber module is lowered, the humidity is lowered to less than 70. It is quite difficult to stabilize it in the state of %(RH).

(Comparative Example 2)

The air compressor, the air volume adjusting device and the humidity adjusting device are sequentially connected through the air supply line. The air compressor and the air volume adjusting device were used in the same manner as in the first embodiment, and were set in the same manner. As the humidity control device, only the circulating constant temperature water tank is used. The temperature and relative humidity of the coating chamber were measured. The results are shown in Figures 11(a) and (b). The temperature in the coating chamber can be seen as a change in the future and in the day. Moreover, the relative humidity in the coating chamber also varies greatly.

10‧‧‧Air compressor

12‧‧‧Compressed air temperature regulator

14‧‧‧Air volume adjustment device

16‧‧‧Air filter

18‧‧‧Humidity control device

20‧‧‧ Coating chamber

21‧‧‧ openings

22‧‧‧Water supply

24‧‧ ‧ wet film device

26‧‧‧ Temperature and Humidity Detector (Temperature Detector and Humidity Detector)

28‧‧‧Control device (1st to 6th control means)

30‧‧‧ Pressure regulating device

200‧‧‧Microneedle preparation system

L‧‧‧Air supply line

Claims (13)

A system for manufacturing a microneedle preparation, which is a system for manufacturing a microneedle preparation for adjusting an air environment in a coating chamber, wherein an air environment in the coating chamber is used for applying a coating liquid containing a drug to a microneedle to manufacture a microneedle preparation And a system for manufacturing a microneedle preparation for adjusting an air environment in a coating chamber, characterized by comprising an air compressor; and for adjusting a humidity of the air supplied by the air compressor, and the air and the humidity adjusting source a moisture permeable membrane type humidity modulating device in which moisture is separated by a moisture permeable membrane; a pressure regulating device for regulating the pressure of the air supplied by the air compressor; and air sterilizing air supplied to the coating chamber filter. The system for producing a microneedle preparation according to claim 1, wherein the moisture permeable film is formed into a hollow fibrillar shape. The system for producing a microneedle preparation according to claim 1 or 2, comprising: a humidity detector; and a first control means for controlling the pressure adjusting means based on a signal corresponding to the humidity detected by the humidity detector. The system for producing a microneedle preparation according to any one of claims 1 to 3, further comprising: a temperature detector and a signal based on a temperature corresponding to the temperature detector to control the second pressure regulating device Control means. The system for manufacturing a microneedle preparation according to any one of claims 1 to 4, Among them, there is provided a compressed air temperature adjusting device that adjusts the temperature of the air supplied by the air compressor. A system for producing a microneedle preparation according to claim 5, comprising: a humidity detector; and a third control means for controlling the compressed air temperature adjusting means based on a signal corresponding to the humidity detected by the humidity detector. The system for producing a microneedle preparation according to claim 5 or 6, wherein the fourth control means for controlling the compressed air temperature adjusting means is provided with a temperature detector and a signal based on a temperature corresponding to the temperature detector . The system for producing a microneedle preparation according to any one of claims 1 to 7, wherein the humidity control device includes a moisture supply device that supplies moisture. The system for producing a microneedle preparation according to claim 8, wherein the moisture supply device is a constant temperature water tank. The system for producing a microneedle preparation according to claim 8 or 9, wherein the moisture supplier is a person capable of adjusting the water temperature. The system for producing a microneedle preparation according to claim 10, comprising: a humidity detector; and a fifth control means for controlling the water temperature of the moisture supplier based on a signal corresponding to the humidity detected by the humidity detector. The system for manufacturing a microneedle preparation according to claim 10 or 11, comprising a temperature detector and a sixth control for controlling the water temperature of the moisture supplier based on a signal corresponding to a temperature detected by the temperature detector means. An air conditioning method for adjusting an air environment in a coating chamber, wherein an air environment in the coating chamber is used to apply a coating liquid containing a medicament to a microneedle to manufacture a microneedle preparation, which comprises: a step of adjusting the humidity of the air sent to the coating chamber by the moisture-adjusting membrane type humidity adjusting device in which the air and the moisture adjusting source are separated by the moisture-permeable membrane; and adjusting the sending by the pressure adjusting device a step of introducing air into the coating chamber; a step of sterilizing the air with an air filter; and a step of introducing the humidity-conditioned and sterilized air into the coating chamber.