JPH0352524Y2 - - Google Patents

Description

[Detailed description of the invention] [Industrial application field] This invention relates to a micro-dispensing device, and more specifically, it is capable of dispensing a small amount of drug solution over a long period of time with a strictly controlled flow rate. Regarding a micro-dispensing device.

[Conventional technology]

In the past, various osmotic micro-dispensing devices have been developed for continuously administering and injecting small amounts of medicinal solutions such as anticancer drugs, analgesics, insulin, heparin, etc. to patients at strictly controlled flow rates over long periods of time. ing.

For example, JP-A-58-58058 and JP-A-58
-Publication No. 54962 discloses a liquid medicine storage chamber having a spout and a liquid-tight movable mover;
an osmotic pressure inducer storage chamber that includes the mover and the semipermeable membrane and stores the osmotic pressure inducer, and a water storage chamber that has the semipermeable membrane and stores water;
Polyethylene glycol with a molecular weight of about 200 to 20,000 is used as an osmotic pressure inducer, water gradually permeates into this polyethylene glycol to expand the volume of the polyethylene glycol, and the expansion of the polyethylene glycol moves the mover, The movement of this mover moves the chemical liquid at a minute speed.
For example, a micro-volume dispensing device is described in which the medicinal solution dispensing rate is varied in steps from 0 to a predetermined value.

It also includes a liquid medicine storage chamber having a spout and a liquid-tight movable mover, the mover and a semipermeable membrane, and houses an electrolyte solution containing an electrolyte solid as an osmotic pressure inducer. A micro-dose dispensing device has also been proposed (Japanese Patent Application No. 62-284835), which includes an osmotic pressure inducer storage chamber and a water storage chamber that stores water through the semipermeable membrane.

[The problem that the idea aims to solve]

However, in such conventional microdispensing devices that use polyethylene glycol as the osmotic pressure inducer, water passes through the semipermeable membrane and moves to the osmotic pressure inducer chamber, causing the polyethylene glycol to The concentration of the aqueous solution decreases moment by moment, and as a result, the concentration of the polyethylene glycol aqueous solution cannot be kept constant until all the chemical solution is poured out, and eventually the water permeation rate decreases, causing the chemical solution to be poured out. There was a problem that the output speed decreased. In order to alleviate this problem, it is necessary to use a large excess of polyethylene glycol aqueous solution, which is inconvenient for downsizing the micro-dispensing device.

Therefore, by using an electrolyte solution containing a solid electrolyte as the osmotic pressure inducer, the volume of the osmotic pressure inducer storage chamber can be reduced, and the micro-dispensing device can be downsized.

However, according to further studies by the present inventor, this micro-dispensing device fills the syringe with a liquid medicine while pulling the mover inside the syringe forming the liquid medicine storage chamber to the end of the syringe with a suction rod. After the suction rod is removed from the movable device, a cartridge consisting of an osmotic pressure inducer storage chamber and a water storage chamber is pushed into the syringe. The inventors have discovered that discharging the drug solution from the spout of the syringe causes waste of the drug solution.

Another method for filling the drug solution is to push the cartridge into the syringe and then use another syringe or the like to fill the drug solution storage chamber with the drug solution, but this method is time-consuming and
A problem arose that it was undesirable from a sanitary standpoint.

Further, in this micro-dispensing device, in order to stably fit the cartridge into the syringe, it was necessary to ensure a certain length in the osmotic pressure inducer storage chamber of the cartridge. Therefore, when the micro-dispensing device is arranged so that the spout of the syringe is located on the upper side and the water storage chamber of the cartridge is located on the lower side, the solid electrolyte in the osmotic pressure inducer storage chamber and The electrolyte component in the electrolyte solution exists near the semipermeable membrane due to the difference in specific gravity, but if the spout is located at the bottom and the water storage chamber is located at the top, the solid electrolyte Also, since the electrolyte in the electrolyte solution moves away from the semipermeable membrane, the concentration of the electrolyte near the semipermeable membrane becomes low, and the permeation rate of water decreases, resulting in a decrease in the pouring rate of the chemical solution. There was a problem.

Therefore, in order to maintain the amount of medicine dispensed at a constant speed, the micro-dispensing device must be arranged so that the spout always faces upward.

However, for example, for reasons of treatment, there are cases where the micro-injection device must be attached to the patient's body, particularly the patient's arm, and in such cases,
As you raise and lower your arm, the spout of the micro-dispensing device points upwards or downwards, and the amount of medicine dispensed changes each time, so in order to maintain the amount of medicine dispensed at a constant speed, The arm of the patient wearing this micro-injection device must be fixed in a certain direction. If the patient's arm is immobilized for a long period of time, the patient will experience great pain.

An object of the present invention is to solve the above-mentioned problems and to provide a micro-dose dispensing device whose dispensing speed of medicinal solution does not practically change even if its posture changes.

Another object of the present invention is to provide a small amount dispensing device that has a simple structure and can directly fill a drug solution storage chamber with a drug solution.

[Means to solve the problem]

To achieve the above object, the present invention has a structure including a drug solution storage chamber having a spout and a liquid-tight movable mover, and an osmotic pressure inducer storage chamber that stores an electrolyte solution as an osmotic pressure inducer. and a water storage chamber for storing water through a semipermeable membrane, an electrolyte tablet is stored in the osmotic pressure inducer storage chamber, and the water in the water storage chamber permeates through the semipermeable membrane. A micro-injection characterized in that the mover moves into the osmotic pressure inducer storage chamber and increases the volume of the electrolyte solution by permeation of water, thereby making it possible to move the mover and pour out a small amount of the drug solution from the spout. It is an output device.

[Effect]

In the micro-dispensing device of the present invention, when a drug solution is stored in the drug solution storage chamber, an osmotic pressure attractant is stored in the osmotic pressure attractant storage chamber, and water is stored in the water storage chamber, the water crosses the semipermeable membrane. It penetrates and gradually moves into the osmotic attractant storage chamber. Inside the osmotic attractant storage room,
Since the electrolyte solution and electrolyte tablets are filled, the permeated water diffuses into the electrolyte solution without causing significant concentration polarization. This water diffusion increases the volume of the electrolyte solution, which moves the mover, and the movement of the mover causes the drug solution in the drug solution storage chamber to be poured out from the spout.

Water that passes through the semipermeable membrane and moves into the osmotic attractant storage chamber does not cause significant concentration polarization in the electrolyte solution, so water passes through the semipermeable membrane at a constant rate, resulting in a practical The chemical solution is dispensed at a constant flow rate.

In addition, when filling the drug solution storage chamber with a drug solution, remove the tube from the osmotic pressure inducer storage chamber, attach a suction device to the end of the removed tube, immerse the spout of the drug solution storage chamber in the drug solution, and use the aspirator. By suctioning, the medicinal solution is directly filled into the medicinal solution storage chamber with a simple operation.

〔Example〕

Embodiments of the present invention will be described below with reference to the drawings.

FIG. 1 is a sectional view showing a micro-dose dispensing device 1 which is a preferred embodiment of the present invention.

As shown in FIG. 1, in this micro-dispensing device 1, inside a cylindrical body 3 having a spout 2 at one end,
A slider 4 is attached to the inner circumferential surface of the cylindrical body 3 in a liquid-tight manner and slidably moves within the cylindrical body 3. A chemical liquid storage chamber 5 is formed by the inner surface of the part and the moving element.

There are no particular restrictions on the material of the cylindrical body 3 in the micro-volume dispensing device 1, which is a preferred embodiment.

However, it is advantageous to form the cylindrical body 3 using a commercially available syringe or the like, since the amount of the medicinal solution to be poured out can be easily checked visually.

The shape and material of the mover 4 are not limited as long as it can move liquid-tightly and slidably into the cylindrical body 3, but usually,
The elastic member can be made of, for example, silicone rubber, butadiene rubber, butadiene styrene rubber, or the like.

In the drug solution storage chamber 5, there is a small amount dispensing device 1.
Various drugs depending on the intended use, such as insulin, antiarrhythmic drugs (e.g. lidocaine),
Contains anticancer drugs, alkylating agents, hormones, analgesics, heparin, etc.

The amount of the drug solution filled into the drug solution storage chamber 5 can be appropriately determined depending on the amount of the drug solution to be poured out. The amount of chemical solution in most cases is 1 to 3 c.c.

On the other hand, an inner cylindrical body 7 has an outflow port 6 at one end and is open at the other end, and an outer cylindrical body 10 whose one end constitutes a support body 9 having a plurality of water passage holes 8 and whose other end is open. are fitted at their respective openings and sealed with a fixing member 11 such as an O-ring.

A semipermeable membrane 13 is stretched across a support body 9 having a plurality of water passage holes 8 through a cloth mesh 12, and the inner cylindrical body 7, the outer cylindrical body 10, and the semipermeable membrane 13 prevent water from permeating. A pressure-inducing agent storage chamber 14 is formed.

The support 9 is not particularly limited as long as it can support the semipermeable membrane 13 and allow water to pass through it. For example, a wire mesh, a synthetic resin net, etc. can be used. As shown in , one having a plurality of water holes 8 is preferably used.

As the semipermeable membrane 13, cellulose acetate, polyamide, etc. can be used, and 0.1
Reverse osmosis membranes with many pores of ~0.7 nm are preferred.

Further, in the device of the present invention, the osmotic pressure attracting agent storage chamber 14 is filled with an electrolyte solution as the osmotic pressure attracting agent.

Examples of the electrolyte include water-soluble alkali metal salts and/or alkaline earth metal salts.

Examples of the alkali metal salts include halides, carbonates, sulfates, and sulfites such as lithium, sodium, potassium, and rubidium, and examples of the alkaline earth metal salts include calcium, Halides such as strontium, barium, carbonates, sulfates and sulfites can be used.

In this invention, any one of the alkali metal salts and alkaline earth metal salts may be used, or they may be insolubilized by reacting with each other, or
Alternatively, at least two of the alkali metal salts and alkaline earth metal salts may be used in combination, as long as the object of this invention can be achieved without generating gas.

Among the various compounds mentioned above, alkali metal halides are preferred, and sodium chloride is particularly preferred from the standpoint of safety and ease of handling.

The electrolyte solution is usually used as an aqueous solution of the alkali metal salt and/or alkaline earth metal salt.

The concentration of metal salt in the aqueous solution is usually 0.3% to
A saturation concentration, particularly a saturation concentration is preferred. In particular, as shown in FIG. 1, when the osmotic pressure attractant storage chamber 14 is filled with electrolyte tablets 15 such as alkali metal salts and/or alkaline earth metal salts, the osmotic pressure attractant storage chamber As a result, the length of the osmotic pressure attractant storage chamber 14 can be reduced, and the concentration polarization of the electrolyte solution within the osmotic pressure attractant storage chamber 14 can be reduced. be able to. Furthermore, it is possible to downsize the device.

Furthermore, in the micro-dose dispensing device 1 of the present invention, a flexible bag body 16 formed of a flexible member is provided on the side of the osmotic pressure inducer storage chamber 14 on which the semipermeable membrane 13 is stretched.
The opening of the flexible bag 16 is connected to the semipermeable membrane 1.
3 is attached so as to cover the support 9 on which it is stretched,
A water storage chamber 17 is configured. Note that the flexible bag 16 is housed in a protective container 18 for protection.

The flexible bag 16 may be anything as long as it can store water, and for example, a bag made of thermoplastic synthetic resin can be used.

The water contained in the flexible bag 16 is as follows:
Examples include tap water, distilled water, and ion exchange water.

The amount of water accommodated in the flexible bag 16 is equal to the amount of liquid medicine required to be poured out, and is usually 1 to 3.
cc.

Next, a chemical solution storage chamber 5 equipped with the mover 4
and the osmotic pressure inducer storage chamber 14 are removably connected by a tube 19 via a rubber stopper 20 and a coupler 21, respectively.

The micro-volume dispensing device 1 configured as described above is used in the following manner.

First, remove the tube 19 from the outlet 6 of the cylinder 3 and the inner cylinder 7, attach the suction device 22 to the coupler 21 of the tube 19, and suck up the electrolyte saturated aqueous solution from the rubber stopper 20 side of the tube 9. (Figure 2).

Next, the rubber stopper 20 of the tube 19 is fitted onto the open side of the cylindrical body 3 having the spout 2 and the slider 4 and forming the liquid medicine storage chamber 5 . In this case, the mover 4 is located on the open side of the cylindrical body 3 (rubber stopper 20
(Figure 3).

Thereafter, the electrolyte saturated aqueous solution is pushed out from the suction device 22, passes through the tube 19, and fills the cylindrical body 3 with the electrolyte saturated aqueous solution. In this case, mover 4
is pushed by the electrolyte saturated aqueous solution and moves to the vicinity of spout 2 (Fig. 4).

Next, the spout 2 is immersed in the medicinal solution to be used, and suction is performed using the suction device 22 until a predetermined amount of the medicinal solution is filled into the medicinal solution storage chamber 5 (FIG. 5).

When a predetermined amount of the chemical liquid is filled into the chemical liquid storage chamber 5,
Remove coupler 21 of tube 19 from suction device 22.

On the other hand, after injecting the saturated aqueous electrolyte solution from the outlet 6 into the osmotic attractant storage chamber 14, the coupler 21 of the tube 19 is connected to the outlet 6, and the micro-dispensing device of the present invention shown in FIG. form 1.

By doing so, the water in the water storage chamber 17 passes through the semipermeable membrane 13 and gradually moves into the osmotic pressure inducer storage chamber 14. Since the osmotic pressure inducer storage chamber 14 is filled with an electrolyte solution, the permeated water diffuses into the electrolyte solution without causing significant concentration polarization. Due to the diffusion of this water, the volume of the electrolyte solution increases, which causes the mover 4 to move, and by the movement of the mover 4, the drug solution in the drug solution storage chamber 5 is poured out from the pouring port 2.

Osmotic pressure inducer storage chamber 14 passes through semipermeable membrane 13
Since the water that has moved inside does not cause significant concentration polarization in the electrolyte solution, water passes through the semipermeable membrane 13 at a constant rate, and as a result, the chemical solution is poured out at a practically constant flow rate.

(Example 1) In the apparatus shown in FIG. 1, a cellulose acetate semipermeable membrane (effective membrane area 0.785
cm ² ), and the support 9 of the semipermeable membrane 13 had seven water passage holes 8 with a diameter of 3 mm. In addition, the volume of the osmotic pressure inducer storage chamber 14 is 0.47ml,
Sodium chloride was used as the electrolyte, and the electrolyte tablet 15 had a diameter of 10 mm, a thickness of 6 mm, and a mass of 0.96 g.

Further, a rubber bag was used as the flexible bag 16, and 2.0 ml of water was filled into the rubber bag so as not to contain air bubbles.

Further, as the cylindrical body 3 forming the drug storage chamber 5, a 2.5 cc commercially available syringe was used, and the slider 4 was made of a suction rubber of a commercially available syringe.

This micro-dose dispensing device was placed in a constant temperature bath at 37° C. with the outflow port 6 facing upward, and changes over time in the amount of water filled instead of the chemical solution were measured.

As a result, as shown by straight line a in Fig. 6,
A pouring volume of 2.0 ml in 24 hours was obtained with practical linearity.

(Example 2) The micro-dispensing device used in Example 1 was placed in a constant temperature bath in the same manner as in Example 1, with the outlet 6 facing down, and water was poured in the same manner as in Example 1. Changes in the amount dispensed over time were measured.

The results are as shown by straight line b in FIG. 6, and an amount of 1.91 ml poured out in 24 hours was obtained with practical linearity.

[Effect of idea]

According to this invention, regardless of the installation orientation of the device, it is possible to keep the amount of medicine dispensed constant over time and dispense a small amount of medicine over a long period of time. It is possible to provide a small amount dispensing device that can simply and easily fill a medical solution storage chamber directly with a medical solution.

Furthermore, if electrolyte tablets are filled in the osmotic pressure attractant storage chamber, concentration polarization of the electrolyte solution can be reduced, and it is also possible to downsize the apparatus.

Furthermore, since the drug solution storage chamber and the osmotic pressure attractant storage chamber are connected by a tube, the installation posture of both can be freely selected, and the shapes of both can be freely selected.

Furthermore, if a single additional injection (bolus injection) is required, the tube can be removed from the osmotic inducer storage chamber, a suction device can be fitted, and the electrolyte-saturated aqueous solution can be injected to move the drug storage chamber. The child can be moved to perform additional injections of the drug solution.

[Brief explanation of the drawing]

FIG. 1 is a sectional view showing a preferred embodiment of the present invention;
FIGS. 2 to 5 are cross-sectional views for explaining how to use the apparatus of the present invention, and FIG. 6 is a graph showing the pouring speed in an embodiment of the present invention. 2... Outlet, 3... Cylindrical body, 4... Mover,
5... Chemical storage chamber, 8... Water hole, 9... Support, 12... Cloth mesh, 13... Semi-permeable membrane, 1
4... Osmotic pressure inducer storage chamber, 15... Electrolyte tablet, 17... Water storage chamber, 19... Tube.

Claims (1)

[Scope of Claim for Utility Model Registration] (1) A drug solution storage chamber having a spout and a liquid-tight movable mover, and an osmotic pressure inducer storage chamber that stores an electrolyte solution as an osmotic pressure inducer. , a water storage chamber for storing water through a semipermeable membrane, an electrolyte tablet is stored in the osmotic pressure inducer storage chamber, and the water in the water storage chamber permeates through the semipermeable membrane to cause the osmosis. A micro-dose dispensing device, characterized in that the movable element moves into a pressure-inducing agent storage chamber and increases the volume of the electrolyte solution due to water permeation, thereby making it possible to inject a micro amount of the drug solution from the spout. . (2) The micro-dose dispensing device according to claim 1, wherein the drug solution storage chamber and the osmotic pressure inducer storage chamber are removably connected to each other by a tube.