WO2009128491A1

WO2009128491A1 - Inhalation aid for metered dose inhaler spray

Info

Publication number: WO2009128491A1
Application number: PCT/JP2009/057635
Authority: WO
Inventors: 朋宏座間; 典子伊藤; 尚本田
Original assignee: 帝人ファーマ株式会社
Priority date: 2008-04-17
Filing date: 2009-04-16
Publication date: 2009-10-22
Also published as: JP5462152B2; JPWO2009128491A1

Abstract

Provided is an inhalation aid which facilitates the synchronization of a spraying procedure with the breath in a metered dose inhaler spray. An inhalation aid for a metered dose inhaler spray which is attached to the metered dose inhaler spray in such a manner as to cover the aerosol container insertion hole of the metered dose inhaler spray to thereby impart an aeration resistance to the metered dose inhaler spray.

Description

Inhalation aid for metered dose inhalers

The present invention relates to an inhalation assisting device for a metered dose inhaler.

For the prevention and treatment of respiratory diseases such as bronchial asthma, drugs using quantitative nebulizers (hereinafter abbreviated as pMDI) (pressurizedhalmetered dose inhaler) are widely used. It was difficult to synchronize, and there was concern that there would be a difference in the degree of drug delivery into the lungs depending on the skill of the inhalation procedure. In addition, when the synchronized inhalation is not successfully performed, the effect is reduced, and local side effects due to the drug adhering to the oral cavity have been problems.

Conventionally, spacers have been used to solve this problem (Patent Documents 1 to 4), but the size is inconvenient to carry, and the deposition of drugs in the spacer over time after spraying is also a problem. Has been. In addition, in order to increase the deposition rate of drugs in the lung, inhalation at a slow inhalation speed is recommended, but there is a problem that it is difficult to control the inhalation speed of the patient.
JP-A-2-291869 Japanese National Patent Publication No. 8-508439 Japanese Utility Model Publication No. 5-7246 Japanese Utility Model Publication No. 6-5642

An object of the present invention is to provide an inhalation assisting device that facilitates the synchronization of the spraying operation and the inhalation in the pMDI.

Furthermore, an object of the present invention is to provide an inhalation assisting device for pMDI that is convenient to carry, does not deposit a drug on the device, and can easily control the inhalation speed.

As a result of intensive studies to achieve such an object, the present inventors have found that by giving ventilation resistance to pMDI, the intake air flow rate is limited and the inhalable time is extended. The inventors have found that the object of the present invention can be achieved by providing ventilation resistance, limiting the flow rate of intake air, and extending the inhalable time, thereby completing the present invention.

That is, the present invention relates to the following.
(1) An inhalation assisting device for pMDI, which is attached to the pMDI so as to cover the pMDI's aerosol container insertion port, and provides ventilation resistance to the pMDI.
(2) The inhalation assisting device according to (1), which is breathable.
(3) The inhalation aid device according to (2), which is made of a breathable material.
(4) Consists of a breathable material or a non-breathable material with holes,
The inhalation assisting device according to (2), wherein the shape when the pMDI is mounted is a bag shape that can cover the aerosol container insertion port of the pMDI in which the aerosol container is installed, including the aerosol container.
(5) Consists of a breathable material or a non-breathable material with holes,
The shape at the time of pMDI wearing is a cylindrical shape that can cover the side of the aerosol container and the adapter,
The cylindrical inhalation assisting device when pMDI is mounted has an inner diameter equal to the outer diameter of the adapter part to which the inhalation assisting device is mounted, and a height that covers at least a part of the pMDI aerosol container and the side surface of the adapter. ,
The inhalation assisting device according to (2), wherein the inhalation assisting device according to (2) has an engaging portion that is configured to extend inward from an end portion of the cylindrical portion as necessary, and can be engaged with an upper end portion of an aerosol container of pMDI.
(6) The ventilation resistance to be applied causes a pressure drop (kPa) of greater than 0 and 13 kPa or less to pMDI when an inhalation aid is attached to the pMDI. The inhalation aid device according to any one of (1) to (5), calculated by -Pb).
Pa: Pressure generated when sucked at 28 L / min Pb: Pressure generated when a metered dose inhaler equipped with an inhalation assisting device is sucked at 28 L / min

According to the inhalation assisting device of the present invention, which is attached to the pMDI aerosol container insertion port and restricts the flow rate of inhalation air by providing ventilation resistance, thereby extending the inhalable time, in the pMDI, the spray operation and the inspiration are synchronized. This makes it possible to obtain an inhalation aid that is easy to carry, convenient to carry, has no drug deposition on the device, and can easily control the inhalation speed. This achieves a certain effect and improved safety by inhaling the appropriate drug of pMDI. Further, when a non-woven material is used as the material of the instrument, it can be expected to avoid antigen mixing into the inhaled air. Furthermore, when the device is configured to expand and contract in response to inspiration, it can be seen that the inspiration is visually due to contraction at the time of inspiration. Can assist in inhalation (spray pMDI).

It is a figure which shows the 1st embodiment of the inhalation assistance device of this invention comprised with the air-impermeable material. It is a figure which shows the 2nd embodiment of the inhalation assistance device of this invention comprised with the air permeable material. It is a figure which shows the 3rd embodiment of the inhalation assistance device of this invention comprised with the air permeable material. It is sectional drawing of pMDI in which the aerosol container was installed. It is a figure which shows the measuring method (apparatus) of the ventilation resistance which an inhalation | assistant assistance tool provides. It is a figure which shows the detail of the apparatus used for the measurement of the ventilation resistance which an inhalation auxiliary device provides.

DESCRIPTION OF SYMBOLS 1 Adapter 2 Aerosol container 3 Spray port of pMDI 4 Aerosol container insertion port of pMDI 5a Inhalation assisting device 5b Inhalation assisting device 5c Inhalation assisting device 6 Film 7 Hole 8 Rubber 9 Cylindrical part of inhalation assisting device 10 pMDI of inhalation assisting device Engagement part with upper end of aerosol 11 pMDI mounting side end of inhalation assisting device 12 pMDI
13 Tube 14 Mouthpiece adapter 15 Flow meter 16 Pressure sensor

Hereinafter, specific examples of the present invention will be described in more detail with reference to the drawings.

The pMDI to which the inhalation assisting device of the present invention can be applied refers to an inhaler in which a certain amount of medicine is sprayed with one push from a medicine can (aerosol container) filled with medicine (FIG. 4). The pMDI is composed of an aerosol container (2) filled with a medicine and an adapter (1) for spraying the medicine in the aerosol container, and the adapter (1) is an aerosol container insertion port into which the aerosol container is inserted. (4) and a spray port (3) through which the drug is sprayed, and has an L-shaped form so that the drug spray and the drug suction from the port can be easily performed.

The pMDI inhalation assist device (5a, 5b, 5c) of the present invention is attached to the aerosol container insertion port (4) of pMDI, and provides ventilation resistance when inhaling with the mouth added to the spray port (3). To limit the intake air flow rate and extend the inhalable time. It is important for the inhalation assisting device (5a, 5b, 5c) of the present invention to have appropriate air permeability. For example, the inhalation resistance is too large to make inhalation difficult, or it is too small to suppress the intake air flow rate. It is necessary not to be not.

Appropriate ventilation resistance to be imparted causes a drop in pressure (pressure difference) greater than 0 and less than or equal to 13 kPa on pMDI fitted with an inhalation aid when suctioned at 28 L / min. It causes a pressure drop of 0.5 to 6 kPa.

The ventilation resistance provided by the inhalation assisting device can be detected by the following procedure using an apparatus as shown in FIG. That is, a cylinder (13) is prepared, and one port of the tube (13) is connected to a suction device via a tube or the like (note that the other port of the cylinder is a pMDI equipped with an inhalation aid to be measured). Connected). A flow meter is installed between the suction machine and the cylinder (13), and a pressure sensor (17) is incorporated in the cylinder (13). The pressure Pa (kPa) in the cylinder when sucked at a constant flow rate (28 L / min) with a suction machine is measured. In the state of being sucked as it is, pMDI (12) equipped with the inhalation assisting device of the present invention is connected to the mouth of the tube, and the pressure Pb (kPa) in the tube is measured. The pressure drop (Pa−Pb) caused by mounting the pMDI mounted with the inhalation assisting device of the present invention on the cylinder can be expressed as a pressure difference (kPa).

Regarding the breathability, the inhalation assisting device (5a, 5b, 5c) may be made of a breathable material, or may be provided with a breathability by adding a hole or a cut to an impermeable material. . Examples of the air-impermeable material include polyethylene, polyester, polyvinyl chloride, and latex films. Moreover, even if it is a breathable material for moderate breathability, what added the hole, the notch | incision, etc. may be used. Nonwoven fabric, woven fabric, etc. are mentioned as an example of a breathable material. Examples of breathable materials include polyethylene, polyester, polyvinyl chloride, and latex. Further, when the woven fabric is composed of nanofibers, it is preferable that when covering the gap between the aerosol container and the adapter, it is stretchable so that it is easy to fix without slipping, and dust and antigen contamination can be avoided during inhalation and inhalation.

FIG. 1 is a view showing a first embodiment of the inhalation assisting device of the present invention, which is made of an air-impermeable material. The inhalation assisting device (5a) has a bag-like shape composed of vinyl (6) having a hole (7) and rubber (8). The first inhalation aid (5a) covers the aerosol container insertion port (4) of the pMDI in which the aerosol container (2) is installed, including the aerosol container (2), and the aerosol container insertion port (4) side. Of the aerosol container (2) and the adapter (1). For the mounting, rubber (8) or the like may be used as shown in FIG. 1, or the elasticity of the instrument itself may be used. In the present specification, a portion where the aerosol container is not installed in the pMDI is referred to as an adapter.

FIG. 2 is a view showing a second embodiment of the inhalation assisting device of the present invention, which is made of a breathable material. The inhalation assisting device (5b) has a cylindrical shape in which the shape when the pMDI is mounted can cover the side surface of the aerosol container and the adapter. The cylindrical portion (9) of the inhalation aid (5b) has an inner diameter equal to the outer diameter of the adapter when pMDI is mounted, and has a height that covers at least a part of the side surface of the aerosol container and the adapter. Further, the inhalation assisting device (5b) is configured to extend inward from the end of the cylindrical portion (9) as necessary, and engages with the upper end of the aerosol container of pMDI (10 ). FIG. 2 shows an inhalation assisting device having an engagement portion. The second inhalation assisting device (5b) is configured such that the pMDI mounting side end portion (11) of the cylindrical portion (9) is fitted into the pMDI in which the aerosol container is installed, and the engaging portion of the inhalation assisting device (5b). (10) is used by pushing and installing until it engages the pMDI aerosol container top. In addition, when the inhalation assisting device (5b) is formed of a stretchable material in a ring shape, the inhalation assisting device (5b) is covered and fixed across the side surfaces of the aerosol container and the adapter so as to cover the gap between the aerosol container and the adapter. You may comprise. The inhalation assisting device (5b) is wound around the side surface of the aerosol container and the adapter so that the gap between the aerosol container and the adapter can be covered with a stretchable material, and a magic tape ( A configuration in which a hook-and-loop fastener such as a registered trademark is provided may be used.

FIG. 3 is a view showing a third embodiment of the inhalation assisting device of the present invention, which is made of a breathable material. The inhalation assisting device (5c) has a cylindrical shape when the pMDI is mounted so that the gap between the aerosol container (2) and the adapter (1) can be filled. The inhalation assisting device (5c) has a thickness that fills the gap between the aerosol container and the adapter when pMDI is mounted, and has an appropriate height to fill the gap stably. In order to make the inhalation assisting device (5c) easy to wear, it is preferably made of a stretchable material.

The present invention is applicable to any pMDI.

EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited thereto.
[Example 1]
The inhalable time was measured using the inhalation assisting device (5a) shown in FIG. The inhalation assisting device (5a) includes a plastic bag (5 cm × 5 cm) (6) having holes (7) opened at several tens of points with a needle and a rubber band (8). The inhalation assisting device (5a) was mounted so as to cover the aerosol container insertion port (4) of the pMDI in which the aerosol container (2: Olvesco (registered trademark)) was installed. The pMDI spray port (3) was added to the mouth, and the time from the start of inspiration until the end of inspiration (inhalable time) was measured. The results are shown in Table 1.
[Comparative Example 1]
The inhalable time was measured in the same manner as in Example except that no inhalation aid was attached. The results are shown in Table 1.
[Comparative Example 2]
The inhalable time was measured in the same manner as in Example except that no hole was provided in the plastic bag. The results are shown in Table 1.

By installing the inhalation assisting device of the present invention, the inhalable time was extended compared to pMDI not equipped with the inhalation assisting device of the present invention (Example 1). During this extended inhalable time, the pMDI spraying operation can be performed. Therefore, it can be seen from Example 1 that when the inhalation assisting device of the present invention is attached to the pMDI, the inhalable time is extended, and as a result, it becomes easier to synchronize the pMDI spraying operation with the inhalation.

Further, from Comparative Example 2, it was confirmed that the inhalation assisting device needs to be breathable.

[Example 2] Pressure difference of inhalation assisting device Nanofront (registered trademark) was used as an inhalation assisting device, and inhalation assisting devices A to F having different inspiratory resistances with materials having different breathability were prepared. As shown in FIG. 2, the inhalation aids A to F have a cylindrical shape that can be covered over the side surfaces of the aerosol container and the adapter and are covered with the aerosol container insertion port.

As shown in FIG. 5, a Teflon (registered trademark) cylinder (inner diameter) is connected to a flowmeter (manufactured by KEYENCE, FD-A50) and a pressure sensor (manufactured by KEYENCE, AP-41). About 30 mm and a length of about 100 mm) were firmly connected so as not to leak air, and the flow rate of the suction machine was adjusted to a predetermined flow rate (15 L / min, 28 L / min, 35 L / min). After that, to prevent air leakage in the Teflon cylinder, firmly attach the pMDI equipped with the inhalation aid of the present invention, and reduce the pressure drop (pressure difference) when sucked with a suction machine. Measurements were made with the attached pressure sensor. The results are shown in Table 2.

[Example 3] Extension of inhalation time with inhalation assist device Ten subjects who were healthy volunteers were not instructed to inhale, and the time required for inhalation was measured by first inhaling pMDI. Thereafter, the pMDI equipped with the inhalation aids A to F was randomly inhaled, and the time required for inhalation was measured in the same manner. Table 3 shows the measurement results. In Table 3, the units of the numerical values in the columns other than the upper inhalation aid / pressure difference all represent seconds.

As a result, it was confirmed that almost all of the pMDIs equipped with inhalation aids had the same or longer inspiratory time. In addition, it was confirmed that the inhalation time was extended as the pressure difference of the inhalation assist device was larger.

[Example 4] Sensory test on resistance feeling by inhalation assisting device Ten healthy volunteer subjects were equipped with inhalation assisting devices A to F, respectively, using pMDI with no inhalation assisting device as a reference for resistance. In addition, the resistance feeling during inhalation of pMDI was arbitrarily described on a straight line, with the level at which the resistance feeling was felt at maximum being 15. The feeling of resistance that I felt acceptable as intake resistance was also described in the same way. Each resistance and allowable resistance are shown in Table 4 as the distance from the lower limit of the straight line.

As a result, it was confirmed that the greater the pressure difference of the inhalation assist device, the stronger the inspiratory resistance during inspiration.

By attaching the inhalation aids A to F to pMDI, in most subjects, the inhalable time was extended as compared with pMDI alone. In addition, since the inhalation aids A to E have many responses that are acceptable, the optimum ventilation resistance suggests that the pressure difference during suction at 28 L / min is about 0.5 to 6 kPa. It was done.

[Example 5] Measurement of particle size distribution when wearing an inhalation assisting device Using pMDI equipped with an inhalation assisting device, particle size distribution was measured by an Andersen Cascade Impactor (manufactured by COPLEY). As the inhalation assisting device, a cylindrical shape capable of covering the aerosol container and the side surface of the adapter and having a shape covered by the aerosol container insertion port and generating a pressure difference of 9 kPa was used. As a result, there was no clear difference in the fine particle amount and distribution (Fine particle dose, Fine Particle fraction) in pMDI with or without inhalation aids. It was estimated that there was no. The particle size distribution was measured according to USP31 <601> AEROSOLS, NASAL SPRAYS, METERED-DOSE INHALARS, AND DRY POWDER INHALERS, and Aerodynamic Size Distribution.

According to the present invention, it is possible to obtain an inhalation assisting device that can be attached to the pMDI, that is easy to synchronize the spraying operation and inhalation, that is convenient to carry, that does not deposit medicine on the device, and that can easily control the inhalation speed. .

Claims

An inhalation assisting device for a metering spray inhaler that is attached to the metering spray inhaler so as to cover the aerosol container insertion port of the metering spray inhaler, and provides ventilation resistance to the metering spray inhaler.
The inhalation assisting device according to claim 1, which is breathable.
The inhalation assisting device according to claim 2, which is made of a breathable material.
Consists of breathable material or impervious material with holes,
The shape when the metered dose spray inhaler is mounted is a bag shape that can cover the aerosol container insertion port of the metered dose spray inhaler in which the aerosol container is installed, including the aerosol container. Inhalation aid.
Consists of breathable material or impervious material with holes,
The shape when the metered dose inhaler is mounted is a cylindrical shape that can cover the side of the aerosol container and the adapter,
The cylindrical inhalation assisting device when the metered dose inhaler is mounted has an inner diameter equal to the outer diameter of the adapter part to which the inhalation assisting device is mounted, and a height that covers at least a part of the side surface of the aerosol container and the adapter. Have
The inhalation according to claim 2, further comprising an engaging portion configured to extend inwardly from an end portion of the cylindrical portion as needed, and engageable with an upper end portion of an aerosol container of a metered dose inhaler. Auxiliary equipment.
When the breathing resistance is applied to the metered dose inhaler with an inhalation aid, the metered spray inhaler causes a pressure drop (kPa) greater than 0 and less than or equal to 13 kPa. The inhalation assisting device according to any one of claims 1 to 5, wherein the decrease is calculated by (Pa-Pb).
Pa: Pressure generated when sucked at 28 L / min Pb: Pressure generated when a metered dose inhaler equipped with an inhalation assisting device is sucked at 28 L / min