JP2003527933A - Drug volume measuring device - Google Patents

Abstract

(57) [Summary] In the first step, a predetermined volume of liquid drug is taken out of the liquid drug container (933) into the volume measuring chamber (950) and controlled, and then in the second step, an injection needle or the like is used. An apparatus and method for a drug delivery system comprising releasing a predetermined volume to a dosing element has been disclosed. The volume measurement chamber (950) operates as a piston / cylinder structure that allows the piston to be progressively retracted to a predetermined degree by a threaded engagement between a manual control element (966) and a threaded piston rod (954). can do. This determines the volume of the drug. Depressing the manual control element (966) disengages the screw engagement and pushes the piston (952) forward by the spring (960) in an attempt to return to its original position, causing a predetermined volume of drug to be dispensed (eg, Needle).

Description

Detailed Description of the Invention

FIELD OF THE INVENTION The present invention relates to the preparation and administration of products, and in particular to the injection of a product into the body of an organism, eg a human.

[0002] Background to this, use a pressure applied by a manual plunger includes a syringe for supplying the liquid from the chamber through the inserted needle subcutaneously, percutaneously supplying drugs to the body of an organism different Various devices have been developed.

Furthermore, it is often known in the art that the shelf life of certain injectable substances such as glucagon used to dissolve blood clots is extended when stored, for example in powder or lyophilized form. Are known. These lyophilized substances (ie drugs or compounds) are currently used by injecting materials that would otherwise be unstable. For example, the freeze-drying method is a method in which the material is rapidly frozen at an extremely low temperature, and then rapidly dehydrated by sublimation under high vacuum. The resulting lyophilized compound is generally stored in glass vials or cartridges which are closed by caps such as rubber stoppers, wall membranes and the like.

Prior to administration, it is necessary to reliquefy a powdered or solid material such as a lyophilized compound. This is accomplished by mixing the solid compound with a suitable diluent or liquid. Reliquefaction generally involves using a syringe with a needle to withdraw the diluent from another vial and inject this diluent into a vial containing the compound. The compound is then thoroughly mixed, typically by shaking the vial by hand,
Use another syringe with a needle to withdraw the volume you want to inject into the patient. Two separate vessels are used so that a person reliquefying a compound will ensure that the proper amounts are mixed and
It must be possible to obtain a mixture of suitable concentration. When using a syringe to mix the diluent and drug, it is difficult to obtain an accurate diluent to drug volume ratio.
Therefore, the exact concentration level of the administered drug may be compromised.

Further, since the diluent and compound are in separate sterile containers, the diluent is manually withdrawn via a syringe and the diluent is re-injected into a container containing solid material such as powdered drug, lyophilized drug. This may compromise sterility and safety due to the use of the syringe.

Due to the increasing use of powdered compounds or lyophilized drugs, for example, it is desirable to provide reliquefied drug delivery systems to both professionals and non-professionals. It is desirable to have a simple and reliable system that facilitates preparation and safe delivery for accurate dosing of reliquefied compounds. Further, it would be desirable to provide a lyophilized drug reliquefaction system that maintains sterility throughout the reliquefaction process. Further, it would be desirable to provide improved transdermal delivery of a drug that allows safe and effective administration by the user.

[0007]   The present application relates to means for controlling the volume of liquid drug administered.

The present disclosure includes systems and methods for delivering a liquid drug to a user. The drug delivery system can include a reconstituted, powdered drug delivery, such as a lyophilized drug, or more generally, a liquid drug delivery and delivery. The powdered drug or lyophilized drug supply further includes a system for reliquefying the powdered drug.

The drug delivery system may further include a pressurized system for pressurizing and delivering the drug to the delivery system or directly for subcutaneous delivery.

The drug delivery system may further include an injector system that contacts the tissue and delivers the drug to the patient or user. In an alternative embodiment, the drug delivery system is
It also includes the administration of removable delivery devices, such as standard syringes, needleless injectors, infusion devices or various types of pumps. Another example uses a pen injector to aspirate liquid drug from the system and then deliver the drug subcutaneously.

A method for delivering a powdered drug, such as a lyophilized drug, comprises pressurizing a diluent solution in a diluent vial. The pressurized system can include a compressed air supply, a chemical gas generator, a collapsible volumetric supply, a bellows canister, a standard syringe or cylinder. However, it is not limited to these. The method can include providing a pressurized diluent solution to the powder drug vial. Another step in the method is the reliquefaction step of the drug, which forms a liquid drug by mixing the powdered drug with a diluent solution. The method further discloses delivering the liquid drug to the injector system or transferring the liquid drug to a removable delivery device. The next step involves injecting the liquid drug into the tissue of the patient or user. The method further includes moving the injection needle from the supply or injection position to the retracted or storage position after the supply is complete. It should be noted that the characteristics of the drug delivery system can be modified in response to the application or delivery of another different drug. For example, the pressurization level can be changed depending on the viscosity level of the drug, and the needle type or length can be changed for subcutaneous injection or intramuscular injection. For example, for subcutaneous injection, the length of the needle is 5 to 12 mm, and for intramuscular injection, the length of the needle can be up to about 3 cm.

The method of delivering a liquid medication to a patient can include pressurizing the liquid medication in the vial using a pressurization system. The subsequent steps are similar to those described above with respect to the method of supplying the powdered drug.

A preferred embodiment of the present invention features an injector system having a curved or u-shaped needle.

Another preferred embodiment of the present invention features an injector system having a straight needle.

Another preferred embodiment of the present invention uses a transfer system to transfer the drug to a delivery device such as a standard syringe with a needle, a needleless pen injector. These devices are
Receive the liquid drug from a container such as a vial containing the liquid drug. The delivery device then delivers the drug to the tissue of the user as described herein.

Another preferred embodiment of the present invention features a coupled system that allows the drug to be reliquefied into a solution, which can then be infused into the user. According to this embodiment, the reliquefied drug delivery system has a housing with a first opening or mouth for receiving a first container containing a solid substance for injection such as a lyophilized powdered drug. It should be noted that this container is a rigid container such as a vial, cartridge containing powdered drug. The housing can further include a second opening or port for receiving a second container containing a fluid that mixes with the material in the first container to form an injectable fluid. The drug delivery system can include a manifold having a first passage in fluid communication with the first container and the second container.
The manifold further includes a second path between the first container and the feed or transfer device. The manifold may further include a communication path to a pressurization system that provides a delivery pressure for delivering the liquid drug. In a preferred embodiment, the entry member is a needle that is in fluid communication with the first container after being moved from a storage position inside the housing to an injection position that extends out of the housing and extends into the body of the user.

A preferred embodiment of the present invention hides the injection needle within the main housing of the drug delivery device except during injection of the drug into the user. This embodiment can include a needle retractor that retracts the needle into the housing after injection to minimize the risk of exposing a contaminated needle to the atmosphere.

According to another feature disclosed herein, the length of the delivery path from the container containing the injectable fluid to the injection needle can be shortened to minimize residual amounts of liquid drug. it can.

The first infusion needle is first arranged to pierce the skin of the human being to be infused and, in parallel, is arranged to be in fluid communication with a first container containing infusible fluid. Preferably.

According to another preferred feature, the container containing the infusible fluid is substantially visible during reliquefaction and infusion so that the user can visually observe this process. The use of a compressed fluid, such as a gas, in a container containing an injectable fluid delivers the injectable liquid through an injection needle to the tissue to which it is injected. In an alternative embodiment, the device has a single port with a compression element, so that a container containing a liquid medicament, such as previously reliquefied material, is inserted into the housing while at the same time providing appropriate dosing over a period of time. It can be pressurized to the pressure required to supply the quantity.

In a preferred embodiment of this system, the device is used with the injectable fluid container oriented vertically during infusion. A gas impermeable membrane, such as a hydrophilic membrane, is placed over the fluid path to reduce the risk of gas being injected into the injection site. The membrane, when wet, minimizes gas flow and preferably blocks gas flow,
On the other hand, the passage of liquid is allowed. The orientation of the rigid vessel must be vertical during reliquefaction to obtain adequate pressurization. In embodiments that include a cartridge with diluent and air, it is not necessary to orient vertically for reliquefaction.

According to another aspect of the invention, the axis of the injection needle is perpendicular to the longitudinal axis of the container containing the injectable fluid. In a preferred embodiment, the container containing the powdered drug or lyophilized drug and the container containing the diluent are inserted into the housing in the same direction along parallel axes.
In other embodiments, the containers are inserted in opposite directions along a common or parallel axis. The system can have a housing aperture, mouth or opening sized to match the size of standard vials and cartridges, so existing vials and cartridges can be used. It is not necessary to mix the contents of the container until just prior to injection. Sterility is maintained before and during the reliquefaction process because the contents of the container only contact the sterile part.

Other improvements that reduce the risk of injecting gas at the injection site, and preferably prevent injection, include the use of membranes that are gas impermeable when wet. In addition, gas impermeable membranes can maintain pressure, so using a pressure system to generate higher delivery forces reduces the delivery time of liquid drug. By placing a membrane, such as a hydrophilic membrane, that is impermeable to gas in the wet state on the drug delivery pathway, the membrane checks the delivery of gas to the user, thus controlling infusion pressure and duration. The required gas can be added to the system. The fluid containing container can be a variable volume container containing a controllable volume of gas, eg, air. This controllable volume of air, fluid, is pumped into the drug container to obtain a pressurized drug to deliver the correct dose over a selected time period. According to another aspect of the invention, a device includes a manifold system that minimizes drug delivery pathways, saves assembly costs, and increases system reliability. The simplicity and flexibility of the manifold system facilitates the use of pre-filled standard cartridges and syringes. In a preferred embodiment, the manifold is a two-piece polycarbonate molding in which two molding elements are ultrasonically welded together. A gas impermeable membrane is attached to or welded to one of the polycarbonate molded pieces.

[0024] Other refinements to deliver the expected precise volume of drug include penetrating members, such as exit spikes, that can be adjusted in height. In an alternative embodiment, the expected precise volume, eg, 50%, 80%, etc. delivery is measured by the volume of residual drug or the use of a removable delivery device such as a standard syringe or pen pump injector. be able to.

Further improvements to the drug delivery system include interlocks and indicators that ensure safe and accurate delivery of the drug. The interlock includes a latch that provides a sequence of operations such as pressurization of the container following the insertion stage of the container, a mechanism that prevents the needle from displacing to the injection position after the first injection. However, it is not limited to these. Indicators include vertical indicators and end of supply indicators.

The housing of the drug delivery device is preferably shaped and designed for one-handed operation. For example, the shape of the bottom surface of the housing is flat so that the device can be placed on a table and operated by a user with one hand. In addition, the device is sized to allow one-handed insertion of the vial and subsequent activation of the device.

In a preferred embodiment, the system housing is lightweight and compact,
It weighs less than 30 grams and has a volume of less than 100 cm ³ . This provides a portable and disposable device that can be disposed of or recycled after being used once and can be easily carried by the user. In addition, the system is capable of self-sufficiency and maintenance of sterility through reliquefaction of fluids such as lyophilized drugs and infusion of liquids. The weight and volume of the system housing is
It should be noted that it may vary depending on the embodiment and the volume of drug delivered to the user.

However, a primary aspect of the present invention is a device for controlling the volume of a liquid drug. The device includes a first chamber containing a liquid drug, a pressure source, a liquid drug volume measurement chamber in fluid communication with the first chamber, and a liquid drug volume measurement assembly. This device can be used, or indeed, can be used in combination with any device for administering or delivering a liquid drug to a mammal, such as the freeze-drying system, infusion system, transfer system, etc. described above. By including such a volume measuring device in any of the same or similar systems claimed and described in WO / 00/29049, which is hereby incorporated by reference (generally Alternatively or specifically) any of the drug delivery systems described can be modified.

It is also contemplated to use the device with other devices and systems such as where a finite volume measurement of liquid drug is required prior to drug delivery or drug infusion pump. Furthermore, it is preferred that the infusion step proceed independently of the volume control device.

[0030]   Aspects of the invention are disclosed in the claims.

These and other objects, features and advantages of the drug delivery system and method, as well as other objects, features and advantages, will be apparent from the following detailed description of the preferred embodiments illustrated in the accompanying drawings. Like reference numerals refer to like parts throughout the drawings. The scale of the drawings is not necessarily constant, but rather focuses on illustrating the principles of the invention.

DETAILED DESCRIPTION The present invention is directed to drug delivery systems and methods. The drug delivery system of the present invention generally provides for delivery of a pressurized drug solution, and in particular for infusion of powdered drug or lyophilized drug that requires reliquefaction. The drug delivery system includes a reliquefaction system, a pressure system to facilitate drug delivery, a transfer system and an injector system. Embodiments of the invention may use only one of the described systems or a combination of these systems, depending on the requirements of the application. For example, the preferred embodiment can deliver liquid drug and does not require reliquefaction. Thus, the drug delivery system and method of the present invention is some system or process described below, or a combination of all systems or processes.

Referring to FIGS. 1A-E, the general operation of the preferred embodiment of the drug delivery device 100 is shown. For the sake of clarity, FIG. 2A-B and FIG. 3A
Sectional views of the same embodiment are shown in FIGS. As clearly shown in FIG. 1A, drug delivery device 100 includes a first member or housing 304 and a connected second member or handle 106. The device 100 includes a diluent 166 in a sterile environment.
A first liquid (eg, a fluid such as sterile water) as a lyophilized drug, compound concentrate 1
It is used to inject the reliquefied lyophilized drug obtained in admixture with a second powder such as 64, eg interferon, into an organism, in a preferred embodiment a human. Conveniently, device 100 utilizes a standard vial or first storage container 102 containing lyophilized drug or compound 164 and a standard cartridge or second storage container 116 containing diluent 166. The device 100 can be formed from inexpensive materials such as plastic, so that it is economically feasible to discard the device after a single injection.

In preparation for administering the drug, the user removes the protective packaging over the device 100. This packaging maintains the sterility of the device 100 before use. In a preferred embodiment of the invention, the cartridge 116 containing the diluent 166 is pre-assembled and locked to the bottom of the housing 304 by the arm 133, as shown in Figures 2A and 2B.

The sterile protector of the vial 102 is removed and then locked onto the top of the housing 304 with a needle 124 from the housing that has penetrated the stopper 112 of the vial, as shown in FIG. 2A. At this stage, the vial 102 is filled with air at ambient pressure. Push the cartridge 116 upwards, ie towards the vial 102. The cartridge 116 is perforated and the diluent 166 is supplied to the vial 102, as partially shown in FIG. 1C. At this stage, there is a fluid such as a gas in the vial 102 as will be described later, and the fluid such as a gas is compressed in the vial 102 by the transfer of the diluent 166 to the vial 102. The user is the device 100
Shake well, which ensures that the lyophilized drug is properly reliquefied. The reliquefied lyophilized drug or injectable fluid is identified by reference numeral 160. At this stage, the drug forming a solution with the diluent is ready for injection.
Vial 102 to ensure that the reliquefied drug is infused using a compressed gas, such as air, and that no gas or air is infused at the infusion site.
Vertical and press the device 100 against the skin of the person to be injected. When the user pushes on the handle 106, the injection needle 130 thereby causes the housing 3 shown in FIG.
3. Move between a first position or storage position inside 04 and a second position or injection position outside the housing shown in FIG. 3C. The needle preferably extends 5-12 millimeters out of the housing 304. The second position of the injection needle 130 is also shown in Figure 1D. At this point, the injection needle 130 is fluidly connected to the vial 102 so that the reliquefied lyophilized drug 160 under pressure from the compressed gas in the vial 102 is delivered to the injection site. Supplied.
The supply of reliquefied lyophilized drug 160 can be completed in 10-30 seconds.

When the handle 106 is released, the mechanism returns to the original position by the mechanism 108 (which will be described in detail later) having the beam flexed. At the same time, a needle retraction mechanism (also described below) locks the injection needle 130 inside the housing 304, thereby reducing and preferably preventing the exposure of contaminated needles. The final stage of operation is shown in FIG. 1E, at which point the device 100 can be safely disposed of.

FIG. 1F is a view taken along line 1F-1F of FIG. 1E, showing the housing 3
The relative position of vial 102 and cartridge 116 within 04 is shown. As shown, the vertical axis of vial 102 and the vertical axis of cartridge 116 are parallel, but offset with respect to their placement within housing 304. This allows the vial 102 and cartridge 116 to be inserted into the housing 304 without interfering with internal components of the device 100, such as the needle retraction mechanism described below.

2A and 2B, apparatus 1 including vial 102 and cartridge 116.
00 shows a cutaway view of 00 along line 2A-2A, 2B-2B of F in FIG. In particular, vial 102 may be a standard vial, typically glass, including a pierceable rubber stopper 112 held in place by an aluminum band or other sealing mechanism 114, such as a 2 milliliter vial. preferable. The upper end of the housing 304 allows the vial 1 to pass by passing the lip of the aluminum band 114 under a pair of spaced arms that project like hooks into the housing.
Includes a groove portion 132 that locks 02 into the housing. Mounted on housing 304 is a first needle 124 or other suitable means, which needle is attached to arm 1
Vial 10 when the vial is inserted into the locked position provided by 33
The second rubber plug 112 is configured to have a hole. The first needle 124 for receiving the diluent from the cartridge 116 has a first passage or tube 1 as shown in FIG. 2B.
A fluid is fluidly connected to 22. Like vial 102, cartridge 116 also includes a standard cartridge (eg, a 2 milliliter cartridge containing about 1 milliliter of diluent) and may include a rubber stopper 118 that is pierced by a second needle 126 or other suitable means. preferable. The second needle 126 is fixedly mounted on the extension or compression element 238 of the housing 304 so that the cartridge is punctured when the cartridge is inserted. The first tube 122 is fluidly connected to the second needle 126. Cartridge 116
When the insert is inserted, the extension member 238 of the housing 304 or the compression element is inserted into the rubber stopper 11.
8 and pushes the rubber stopper 118 toward the bottom of the cartridge 116. In this way, the diluent 166 is forced up the tube 122 and into the vial 102,
It is mixed with the drug 164 contained therein. In a preferred embodiment of the invention, the cartridge 116 contains about 1 milliliter of diluent, which is forced into the vial 102 to bring the internal pressure of the vial 102 to about 2.25 bar. This pressure can be adjusted, for example, by reducing the amount of diluent or air in the cartridge 116. By increasing the internal pressure of the vial 102, the reliquefied drug 160 can be injected at a higher speed.

In this way, a sterile solution is provided in which the diluent 166 is mixed with the lyophilized drug 164 with minimal exposure to external contaminants. During reliquefaction and infusion, vial 102 containing reliquefied lyophilized drug 160 is visible, resulting in lyophilized drug 160 being thoroughly mixed with diluent 166, and injecting compressed gas. To ensure that the site has not been infused, it is preferred that the user be able to visually see and confirm that the vial 102 is vertical during the infusion.

The handle member 106 is connected at its first end to the housing 304 by a pivot mechanism 110, which may include rivets or other suitable means, so that the handle member rotates in the direction of arrow 240. To do. Handle member 106
Includes a mechanism 108 that causes the handle member to resiliently deflect the beam so that the end opposite the connected end is forced away from the housing 304. The beam flexure mechanism 108 includes an extension member extending from the handle member 106 and in contact with the housing 304 so that the elastic deformation force away from the housing when the handle member is pushed toward the housing. Provided.
Alternatively or in addition, the beam flexing mechanism 108 may be provided in the housing 3
A conventional spring or other suitable means inserted between 04 and the handle member 106 to provide a deforming force may be included.

In FIG. 2A, the reliquefied drug 160 is further injected into the human body and the housing 3
A needle injection / retraction mechanism for retracting the injection needle 130 is shown inside 04. In this mechanism, the first end is connected by a member 136, the second end is a pin,
It includes a first bar member 140 that is inductively attached to the handle member 106 by a first coupling device 142 such as a rivet, bolt or other suitable means. The member 136 fixedly supports the injection needle 130 and is guided by an opening 138 in the housing 304 or a needle opening. In the preferred embodiment of the invention, the injection needle 130 is a 24-28 gauge needle. The movement of the first coupling device 142 is controlled by the J-shaped slot 134 of the handle member 106, which may include a slot or slot. The second bar member 148 has a first end connected to the first coupling device 142 and a second end connected to the third bar member 152 by a third coupling device 150. The third bar member 152 fixedly supports the third needle 128 and is guided by the inner bore of the housing 304. A second passage or tube 120 fluidly connects the third needle 128 and the injection needle 130. The length of the tube 120 is preferably as short as possible so that less drug remains in the tube after injection and dose accuracy is increased.

The operation of the drug supply device 100 shown in FIGS. 2A and 2B is shown in FIGS.
FIG. 3A shows the stage when the cartridge 116 is inserted and the diluent 166 is forced up the tube 122 into the vial 102. Recall that the rubber bung 118 of the cartridge 116 as shown in FIGS. 2A and 2B is pushed into the bottom of the cartridge by the member 238. This causes diluent 166 to
And thus reliquefied drug 160 is under pressure, in the preferred embodiment about 2.25 bar. The device 100 is preferably shaken vigorously to ensure that the lyophilized drug is properly mixed with the diluent 166.

In FIG. 3B, the device 100 is pressed against the skin of the human to be injected. The user pushes the handle member 106 toward the housing 304 in the direction indicated by arrow 240A, thereby causing the injection needle 130 to move to the first position within the housing.
To a second position outside the housing so that the needle penetrates the skin to be injected.

As shown in FIG. 3C, if the handle 106 is continuously pushed toward the housing 304, the first bar member 140 slides up the J-shaped groove hole 134. at the same time,
The second bar member 148 including the straight groove 244 rotates to rotate the first connecting device 1
42 slides up to the top of groove hole 244.

FIG. 3C shows a state where the handle member 106 is continuously pushed toward the housing 304. As the handle member 106 continues to pivot, the second bar member 148 moves to the third position.
Of the bar member 152 and thus the third needle 128, resulting in the third needle penetrating the rubber stopper 112 of the vial 102. Due to the pressure on the reliquefied lyophilized drug 160, the drug 160 will be extruded through the tube 120 and thus injected into the injecting human. At this point, the beam bending mechanism 108 is compressed. When the hand is released from the handle member 106, an arrow 240
Biasing mechanism 108 pushes the handle member away from housing 304, as indicated by B, retracting the injection needle into the interior of the housing.
This is shown in Figure 3D. The J-shaped slot 134 beneficially comprises an end lock portion 146 that captures the coupling device 142, so that the injection needle 1 after a single injection.
30 is "locked" in housing 304. The device 100 can now be safely disposed of.

4A-K, a drug delivery device 100-1 according to a preferred embodiment of the present invention.
Indicates. The same reference numbers refer to the same or similar elements. Specifically, A of FIG.
Shows a device 100-1 that includes a housing 304-1 having a first port or opening 176 for receiving a diluent cartridge 116 and a second port or opening 262 for receiving a vial 102. In this embodiment, the cartridge 116 containing the diluent 166 is preferably pre-assembled, so that
Needle 126-1 partially penetrates the cartridge and device 100-1 (without vial 102) is packaged with packaging material to maintain sterility prior to use. Again, it is preferable to use a standard 2 milliliter vial and a cartridge containing 1 milliliter of diluent. The user opens the package and inserts vial 102 containing lyophilized drug 164 into opening 262. Alternatively, in FIG.
The vial 102 and the cartridge 116 are packaged separately from the apparatus 100-1 as shown in FIG. The user removes the sterile protector, and the needle 124-1 inserts the rubber stopper 1 into the rubber stopper 1.
Firmly press the vial 102 into the opening until it penetrates 12. The user then pushes the cartridge 116 into the housing 304-1. When the cartridge 116 is pushed into the housing 304-1, the needle 126-1 is first moved to the first position.
Of the rubber stopper 118, resulting in the needle extending into the diluent 166. This stage is shown in Figure 4B.

When the cartridge 116 is further inserted into the housing 304-1, the rubber stopper 118 is pressed against the bottom of the cartridge as shown in FIG. 4C. That is, the first opening 176 of the housing 304-1 is preferably circular so that the wall of the cartridge 116 can enter the housing but not the rubber plug 118. This pushes the diluent 166 out through the needle 126-1 into the manifold or communication passage 168 and then into the vial 102. Again, it is preferred that the reliquefied lyophilized drug 160 in vial 102 be subjected to a pressure of about 2.25 bar. Higher or lower pressures may be required depending on the volume injected. Device 100-1 is preferably shaken vigorously to ensure that the reliquefied lyophilized drug 160 is properly mixed in the pre-injection stage.

It is preferable to insert the vial 102 containing the lyophilized drug 102 before inserting the cartridge 116 containing the diluent 166 so that the diluent does not overflow into the opening 262. To ensure proper insertion order of vial 102 and cartridge 116, an interlocking mechanism is provided according to another aspect of the invention. The interlock mechanism includes a bar member 266 pivotally connected to housing 304-1 between openings 176 and 262. The bar member is configured to move in the direction of arrow 264 (A in FIG. 4) when the vial 102 is inserted. Therefore, FIG.
The bar member 266 prevents the cartridge 116 from being inserted, as shown in FIG. When the vial 102 is inserted, the bar member 266 rotates in the direction of the arrow 264 shown in FIG. 4A, so that the cartridge 116 can be inserted.

As shown in FIG. 4B, device 100-1 further displaces injection needle 130-1 between a first position inside housing 304-1 and a second position outside the housing. An actuator or pushing member 174 is provided. Injection needle 130-1
Preferably extends 5-12 millimeters out of housing 304-1. Infusion needle 130-1 is a 24-28 gauge needle, preferably a "U" shaped needle having a second end 172 configured to pierce seal member 170. The seal member 170 can be any pierceable material such as butyl rubber to hermetically retain the liquid on top of the housing 304-1 prior to use.

In order to prevent the compressed gas in the vial 102 from being injected, the device 100-
The displacement of the injection needle 130 is preferably prevented when the orientation of 1 is incorrect, eg upside down. In addition, to reduce exposure to contaminated needles, 1
The injection needle 130-1 is preferably locked inside the housing 304-1 after a single injection. Further, the needle 130-
It is preferable that 1 is not displaced. A lock assembly 268A is provided to accomplish the above.

Lock assembly 268A has a first end configured to be moved by pushing member 174 and a second end configured to displace ball 270 or other suitable movable locking device. A member 268 as shown in FIG. 4C.
including. When the pushing member 174 is in the first position so that the injection needle 130 is inside the housing, the groove 272 of the pushing member 174 is aligned with the groove 274 so that the ball 270 is free along the groove 274 of the pushing member. Can be moved to. When the vial 102 is oriented vertically and the compressed gas is above the liquid, ie, properly positioned for infusion, as shown in FIGS. 4B and 4C, the ball 270 is at the bottom of the groove 274. Yes, pushing member 174
Can displace the injection needle 130. If the vial 102 is not properly placed (eg, if the assembly is placed upside down as shown in FIGS. 4E and F, which may result in compressed gas injection), the ball 270 may have a groove 272. And 274 to prevent displacement of the pushing member 174. The lock assembly 268A may also be configured so that the pushing member 174 can only be displaced after the cartridge 116 has been inserted. This aspect of the invention is shown in FIGS. Specifically, G of FIG. 4 is similar to C of FIG. 4, but cartridge 116 is shown outside housing 304-1. 4H is a cross-sectional view taken along line 4H-4H of FIG. 4G, showing a locking mechanism member 276 having a slotted portion 278 therein. Member 2
76 is slidable within housing 304-1 and is configured to move upon insertion of cartridge 116. The lower end of member 276 is located in grooves 272 and 274, as shown at I in FIG. Therefore, the member 276
When the cartridge 116 is in the position shown in FIG.
Prior to insertion into 1, the pushing member 174, ie the injection needle 1 associated therewith,
30-1 is prevented from moving to the injection position. When cartridge 116 is fully inserted into housing 340-1 as shown at J in FIG. 4, member 276 moves downward as shown at K in FIG. As shown in FIG. 4L, this causes the slotted portions 278 to align, which results in the pushing member 174, and thus the injection needle 13.
0-1 will be able to move to the injection position.

As shown by M in FIG. 4, the device 100-is installed so that the vial 102 is oriented vertically.
Once properly held, the user pushes on the pushing member 174 so that the injection needle 130-1 first extends out of the housing 304-1 and thus penetrates the skin of the person to be injected. When the pushing member 174 is further pressed, the injection needle 13
A second end 172 of 0-1 punctures the seal member 170, which allows the pressurized reliquefied lyophilized drug 166 to travel from the vial 102 into the infused human body. It takes, for example, 10 to 30 seconds to supply the infusion fluid. This pressing movement compresses the spring 190 so that when the pushing member 174 is released, the member returns to its original position, i.e. the needle 130-1 is moved to the housing 304.
It retreats inside -1, and is locked in it. Inserting the pushing member 174 into the housing 304-1 also moves the member 268 inward, so that the balls 270 exert an eccentric load on the pushing member. This is shown at N in FIG. When the pushing member 174 returns to the first position, the member 268 retains the ball 270 in the groove 272, which prevents displacement of the pushing member or associated needle 130-1 after a single injection. To be This configuration is shown at O in FIG. Device 100-1 can be safely disposed of because injection needle 130-1 is locked within housing 304-1.

5A-5C, drug delivery device 100-2 according to a preferred embodiment of the present invention.
Indicates. Specifically, in FIG. 5A, the cartridge 116 is attached but not inserted, that is, the needle has not entered, and the vial 102 is only inserted at a predetermined position. The device 100-2 is shown in a state. In FIG. 5B, the vial 102 is inserted, and in FIG. 5C, the cartridge 116 is inserted subsequently. At this stage, the diluent in cartridge 116 has been transferred to vial 102 so that there is pressurized liquid in the vial. Shake device 100-2 vigorously to ensure proper mixing of the reliquefied lyophilized drug. Device 100-2 is now ready for injection. Housing 304-2
Note that it is advantageous to include a cutout portion 254. This cut-out allows the user to visually inspect the vial 102 to ensure that the lyophilized drug 160 is well mixed with the diluent 166 and that no air is infused at the injection site. It can be seen that the orientation of vial 102 is vertical during the injection.

FIGS. 6A-6C are plan views of a similar device 100-3, corresponding to FIGS. 5A-5C, respectively. Thus, FIG. 6A shows needle 126-3, although attached.
Shows the cartridge 116 not perforated. Also shown is vial 102 containing lyophilized drug 164 and ready for insertion into housing 304-3.

FIG. 6B shows vial 102 after insertion, pierced by needle 124-3. The vial 102 first pushes against the surface 178-3 of the punching device 182-3 and the needle 1
The device 182-3 is pushed downwards before being punctured by 24. Pushing the piercing device 182 downward sets a spring that moves the piercing device upward (as described below in FIGS. 7A-7C), causing the needle 128-3 to enter the vial 102. Alternatively, the spring can be preloaded. As shown, needle 124-3 and needle 126-3 are fluidly connected by a path 127 or a manifold 127 that includes a tube. When the cartridge 116 is inserted, the rubber stopper is first pierced by the needle 126, and the cartridge 116 is inserted into the circular opening 176-of the housing 304-3.
3 further pushes the rubber stopper 118 up to the bottom of the cartridge 118, which causes the diluent 166 to pass through the manifold 127 and into the vial 102.
Sent to. Furthermore, the gas contained in the vial 102 is compressed to a pressure sufficient for injection. The resulting stage is shown in FIG. 6C. The device 100-3 is preferably shaken vigorously to ensure proper mixing of the lyophilized drug 164. The device 100-3 is now ready to inject the reliquefied drug solution 160 contained in the vial 102.

7A to 7C, the device 100-2 shown in FIGS. 5A to 5C and 6A to 6C,
100-3 shows a partial perspective view of 100-3. Specifically, FIG. 7A shows a pushing member 174-3 that includes an internal bore that slidably includes a member 252 therein. Member 252
Fixedly supports an injection needle 130 in fluid communication with the needle 128 via a tube or path 120. The needle 128 shown in FIG. 7A is still in vial 1.
No hole is made in the rubber plug 112 of 02. The needle 128 is fixedly supported by the punching device 182. Pushing member 174-3 to housing 304-3
Pushing toward (ie, in the direction of arrow 180) compresses the first spring 190, which allows the member 252 to move downward until it contacts the housing. This allows the injection needle 130-3 to extend outward from the needle opening 256 of the housing 304-3 and penetrate the skin of the person to be injected. Spring 19
Zero is set to produce both axial and rotational movement. Vial 102
The rotational movement of the spring is possible only when the is fully inserted, which allows the vial 102 to be punctured. In the preferred embodiment, the injection needle 130.
-3 extends 5-12 millimeters out of the housing through needle opening 256. The injection needle 130 that extends partway from the housing 304-3 is shown in FIG. 7B.

Further pushing of the pushing member 174 toward the housing 304-3 compresses the spring 200, which is stiffer than the spring 190, and allows the ridge 258 of the pushing member 174-3 to contact the punching device 182. . As a result, FIG.
The drilling device 182 rotates in the direction of the arrow 186 indicated by C in FIG.
78 is no longer in contact with vial 102. The spring 190, which is pre-loaded during insertion of the vial 102 as described above, then causes the piercing device 182 to rotate in the direction of arrow 184, which causes the needle 128 to penetrate the rubber stopper 112 of the vial 102. This arrangement is shown in Figure 7C. The reliquefied drug 160 is delivered to the person to be injected through the injection needle 130 by the compressed gas in the vial 102 to about 10 times.
Infused between ~ 30 seconds.

8A-8F, drug delivery system 100 according to a preferred embodiment of the present invention.
-4 is shown. The same reference numbers refer to the same or similar elements. Specifically, FIG.
A shows apparatus 100-4 including a housing 304-4 having a first port or opening 176-4 for receiving a cartridge 116 and a second port or opening 262-4 for receiving a vial 102. .

Inserting vial 102 containing reliquefied drug 164 into housing 304,
Subsequently, the cartridge 116 containing the diluent 166 is inserted. In this case, too,
The rubber stopper of the cartridge 116 is pressed against the bottom of the cartridge, which delivers the pressurized diluent to the vial 102. This stage is shown in Figure 8B. Advantageously, housing 304-4 includes cutout 400 so that vial 102 is substantially visible during reliquefaction and injection. This allows the user to visually confirm that the drug is properly reliquefied and that the vial 102 is vertically oriented during the infusion and that the compressed gas is above the reliquefied drug. be able to.

FIG. 8C is a rear view of FIG. 8B showing injection of reliquefied drug. Specifically, if the pushing member or actuator 174-4 is the housing 3
04-4, which causes injection needle 130-4 to exit the housing and enter the human body to be injected. In a preferred embodiment, the injection needle extends 5-12 millimeters out of the housing. The reliquefied drug in fluid communication with the vial 102 moves from the vial to the person to be infused. 8D-8F are isometric views of apparatus 100-4 at the stages illustrated in FIGS. 8A-8C, respectively.

10A and 10B are graphs showing the system characteristics of the preferred embodiment of the drug delivery device. In order to effectively deliver the specified amount of fluid and to minimize patient discomfort, the system should provide sufficient fluid pressure in the supply vial manually activated by the user for a short time. I need. FIG. 10A shows the pressure (mbar) and weight (gram) characteristics of the system during delivery of about 1.6 milliliters of fluid over about 30 seconds. FIG. 10B shows the test results of using a single drug delivery device to deliver 1.6 milliliters to different animals at the same time.

Referring to FIGS. 11A-11D, there are cut-away views of a preferred embodiment of a diluent container subassembly and manifold that can be used with a drug delivery device or with a conventional syringe or other drug delivery device. It is shown. The diluent container subassembly 300 includes a pre-assembled compression that allows a user to hold a diluent container 312 (which may be in the form of a compressible sealed bag) and insert it into the needle 314. Includes portion 310. Diluent container 312 contains about 1 diluent
It contains a milliliter and a controlled amount of gas, such as air, and is punctured by needle 314 when inserted into housing 304-6. The shelf life or shelf life of diluent container 312 is sized to allow the container to expand as a result of environmental changes. In addition, during the feeding of the diluent for mixing, the compression part 3
Use 10 to compress the outside of the diluent container and apply pressure to the contents of the container. Diluent containers are made of flexible, collapsible materials such as polyethylene, polypropylene,
Formed from nylon and the like. The compression portion 310 includes a slider element 316 and two arms 318, 320 extending longitudinally therefrom. Vertically extending arm 318
Two cylindrical drums 322, 324 are spaced between and 320.

FIG. 11A shows a diluent container subassembly 300 located within the housing 304-6 of a drug delivery system according to the present invention. FIG. 11D shows the preferred embodiment 300 of the diluent container subassembly fully compressed. The slider element 316 of the compression portion 310 translates along at least one axis, eg, in the illustrated embodiment, the slider element can move up or down. When the slider element 316 is moved downwards, the diluent container 312 wraps around the cylindrical drum 324, which compresses the contents of the diluent container 312 and thus the diluent from the container 312 into the vial 102 via the needle 314. Send in. Slider element 316
The movement of the is limited by the end of the moving position. The slider element 316 can be locked by a locking mechanism that ensures that the diluent container remains compressed at this end of the travel position.

Manifold 330 includes two needles 314, 332 fixedly attached to opposite ends of extension member 334. The needles can further include an intrusion member formed from an injection molded material having the level of rigidity necessary to penetrate the vial or container, such as medical grade polycarbonate, acrylic resin, or the like. Pathway 331 provides fluid communication between needle 314 and needle 332.
The needle 314 pierces the container when the diluent container 312 is inserted and the needle 332
The vial is punctured when the vial 102 containing the lyophilized drug 164 is inserted. In a preferred embodiment of the present invention, container 312 contains about 1 milliliter of diluent and a controlled amount of air that is dispensed into vial 102, resulting in
The internal pressure of the vial 102 is approximately 2.25 bar. The internal pressure of vial 102 is due to the controlled amount of air in diluent container 312 being pumped into the fixed volume of vial 102. Thus, diluent 166 is delivered to vial 102 and mixed with lyophilized drug 164 contained therein. It is preferred to shake the entire assembly to ensure that the drug 160 formed for injection is properly mixed. To ensure that no air is injected into the injection site,
The orientation of vial 102 is vertical during injection.

Referring to FIG. 11C, the injection needle 130-6 is shown in a first position inside the housing 304-6. As described above, the injection needle 130-6 has 24
A ~ 28 gauge needle, preferably a "U" needle, having a second end 172-6 configured to pierce the seal member 170-6. A region 171 is located adjacent to the seal member 170-6, and this region is located in the path 3 shown in 11B.
It communicates with 31.

When the user presses the button 305, the needle 130-6 penetrates the skin and the second end 1
72 penetrates into the seal member 170-6. The drug / diluent solution flows from needle 332 through path 331 and region 171 to the user via injection needle 130-6.
When the user presses the button 305 that is spring-loaded by the spring 306, as shown in FIG.
A pair of mating pawls 307, 308, shown at 1C, fit together to prevent the button from being pulled out and prevent reuse of the device.

FIGS. 12A and 12B show a perspective view of the preferred embodiment 300 of the diluent container subassembly and details of the components of the compression portion 310. The cylindrical drum 324 is slotted so that a diluent container can be inserted therein.
The cylindrical drum 322 acts as a backing drum. Therefore diluent container 31
2 is generally inserted between the cylindrical drum 324 and the backing drum 322. The drum devices 322 and 324 are moved by a rack and pinion gear device 340. The travel position end 342 of the rack and pinion gearing 340 restrains the movement of the cylindrical drum 324 at its travel position end. This transfer end correlates to the end of wrapping of diluent container 312 around the cylindrical drum and maximum compression of the container contents. The collar 344 may be used to hold the diluent container 312 on the bottom surface of the subassembly 300. The diluent container 312 can be sealed to the collar 344 by thermal welding or ultrasonic techniques after being filled with diluent. The longitudinally extending arms 318, 320 of the compression portion 310 include two members 350, 352, respectively, as shown in Figure 12B. A cylindrical drum is attached to each member. The two members 350, 352 are spaced from each other to accommodate the diluent container wrapped around the cylindrical drum 324.

Referring to FIGS. 13A and 13B, there is shown a cutaway view of an alternative embodiment of the present invention that includes a manifold 350, similar to the embodiment shown in FIGS. Manifold 350 has two needles 352, 354 for the purpose of piercing vial 102 and diluent container 312, respectively. When the diluent 166 and a controlled amount of air are forced into the vial 102, the diluent will lyophilize the drug 164.
And the resulting reliquefied drug 160 under pressure. Since the reliquefied drug is pressurized by a controlled amount of air, the reliquefied drug is injected into the injection target via the needle 352 and the needle 351 operated by the movement of the pushing member 353. Sent to humans. Reliquefied lyophilized drug 16
The device of this embodiment provides comfort to the user, as it does not require vigorous shaking to ensure that 0 is properly mixed for injection. The controlled amount of air facilitates mixing of the diluent with the lyophilized drug. The pushing member 353 displaces the injection needle 351 between a first position inside the housing 304 and a second position outside the housing or a pouring position.

In order to prevent the compressed gas in the vial 102 from being injected, the device 100-
It is preferable that the displacement of the injection needle 351 is hindered when the 7 is not arranged in an appropriate orientation, for example, when it is arranged upside down. Furthermore, in order to reduce and preferably prevent exposure to contaminated needles, the injection needle 3 after injection once
It is preferred that 51 be locked inside housing 304-7. Furthermore, it is preferable that the needle 351 can be displaced only after the diluent container 312 has been inserted. Therefore, in order to achieve the above, a locking mechanism is provided that includes the member 268 shown in FIG. 4B. The member 268 is a pushing member 353.
Has a first end configured to move and a second end configured to displace a movable locking device substantially similar to the device shown in FIG. 4B.

Once the device 100-7 is properly held so that the vial 102 is oriented vertically, the user pushes on the pushing member 353 so that the injection needle 351 first extends out of the housing 304-7 and then First, it is intended to invade the human skin to be injected. When the pushing member 353 is further pressed, the second end portion 35 of the injection needle 351 is
5 punctures sealing member 357, which allows pressurized reliquefied drug 166 to be delivered from vial 102 to the person to be infused. It takes, for example, 10 to 30 seconds to supply the infusion fluid. This pressing movement compresses the spring 359 so that upon release of the pushing member 353 the member returns to its original position, ie the needle is retracted into the housing 304 and locked.

Referring to FIG. 14A, there is shown a cutaway view of the manifold of another preferred embodiment 100-8 of the drug delivery device according to the present invention. Manifold 350 has two needles 352 for the purpose of piercing vial 102 and diluent container 312, respectively.
354. A collar similar to the collar 127 shown in FIG. 6B has a container 31.
Hold the wall membrane or plug 313 in place in 2. An extension member or communication chamber 356 in fluid communication with the needles 352, 354 has a hydrophilic membrane, barrier 360, or other membrane disposed therein. It should be noted that the hydrophilic membrane needs to be wet in order to minimize and preferably prevent the inflow of gas into the user's tissue. The hydrophilic membrane allows the gas, eg air, to pass freely until it comes into contact with the liquid and becomes wet. Thus, when wet, a controlled amount of air, such as air, in the diluent container 312 cannot pass through the hydrophilic membrane, preventing air from entering the user's tissue. The presence of the hydrophilic membrane prevents the risks caused by the incorrect use of the device 100-8 by the user, such as misplacement of vials or containers.

Referring to FIGS. 15A and 15B, there is shown a cutaway view of another preferred embodiment of a drug delivery device manifold in accordance with the present invention. Needle 352 pierces vial 102 and needle 354 pierces diluent container 312. Needle 354 and spike 352
The A path 352 is in fluid communication with the path 352. Diluent 166 is diluent container 3
Transferred from 12 to vial 102 and thus mixed with lyophilized drug to obtain reliquefied drug. The path 358 has a region 361 sealed by the plug 313.
Is in communication with. Path 358 also includes a hydrophilic membrane. Thus, when air is introduced into the path, the membrane expands in the presence of air and blocks the passage of air.

In use, the user presses the button 363, which first causes the injection needle 13
0-9 migrate into the user's skin. Further movement of button 363 causes piercing member 172 to penetrate plug 313. This allows the liquid drug / diluent solution to travel through the injection needle 130-9 to the user's skin via air pressure in the vial 102.

The position-independent embodiment shown with respect to FIGS. 15A and 15B blocks the flow of liquid through the gas impermeable membrane until all drug solution has been transferred out of vial 102. Note that it is not affected by normal air.

FIG. 15A shows the position of path 358 relative to path 352. Therefore, air enters path 358 only when vial 102 is completely filled with air.
In contrast, the embodiment without the lower path 358 shown with respect to FIG.
It is affected by air which blocks the flow of liquid through the gas impermeable membrane.

Furthermore, it should be noted that the drug delivery time depends on the adjustable vial volume. The pressure is adjusted in part by adjusting the vial volume. It is believed that if the volume of air in the vial is greater than the drug, the air pressure will be higher and the drug delivery will be faster.

In a preferred embodiment of the invention, drug vials and diluent containers are inserted into housing 304 and aligned in the same direction along parallel axes. As an alternative, it is contemplated that the vial and container are not aligned in the same direction along parallel axes. The vial and container can be inserted along two different axes that are beveled or at right angles to each other.

Referring to FIG. 16, a preferred alternative embodiment 236 of the injection device according to the present invention.
A cutaway view of is shown. Device 236 facilitates aseptic injection of filled cartridges or vials containing injectable liquid, eg, vials containing liquid drug 160. The device 236 includes a manifold 370 that includes a first opening 161 for receiving the vial 102 and a member 372 in sealing engagement with the first opening 161.
Member 372 fixedly supports needle 374 and is supported by a collapsible volume such as bellows 378, or other device capable of injecting a fluid such as a gas when compressed. The check valve 380 ensures that the flow from the bellows is unidirectional, that is, no pressurized drug will enter the bellows 378. The check valve 380 includes a tubular member 381 adapted to supply gas, eg, air, to the vial 102. Compressing the bellows 378 causes air to move from the bellows to the tubular member 332. The check valve 380 is a bellows 378.
Allows air to flow from the vial to the vial, but does not allow backflow of air from the vial to the bellows. Air from bellows 378 enters vial 102 through needle 374 and pressurizes the contents of vial 102. The liquid drug 160 is under pressure and is injected directly from the vial 102 into the user. The injection process is similar to the process discussed above with respect to the embodiment of FIGS. 13-15 in that it is injected into the skin using a U-shaped needle assembly. As discussed above, the hydrophilic membrane 3 on the drug supply route
60 minimizes and preferably blocks the injection of gas into the user.

Referring to FIGS. 17A-C, there is shown a cutaway view of an alternative embodiment of the drug delivery device 100 in accordance with the present invention. The diluent container includes a syringe 390. Upon application of pressure to the plunger shaft 392, the diluent 166 travels from the syringe 390 through the path 398 and through the member 398 to permit fluid flow between the needles 3.
94, 396 and into the contents of vial 102. Therefore,
Diluent 166 is delivered to vial 102 under pressure and mixed with the reliquefied drug,
A reliquefied drug solution ready for pressurized infusion or delivery to the patient. The drug solution is delivered to the user using the u-shaped needle assembly disclosed in FIGS. 13A and B, FIG. 14A, and FIG. 15A and B. This syringe embodiment facilitates the use of standard filled containers or cartridges containing diluent only. The device is flexible and requires no special means or training.

The present invention includes a preferred alternative embodiment of the infusion device. 9A-F of the drawings, a filled cartridge or vial containing an injectable liquid, eg, reliquefied drug 16
5 shows an injection device 236 that facilitates aseptic injection of vials containing zero. This device 23
It is preferred to use standard vials with 6, eg 2 ml vials. As shown in FIG. 9A, the device 236 includes a manifold including a first opening for receiving the vial 102 and a member 232 slidably and sealingly engaged with the first opening. The member 232 fixes and supports the needle 224, and the bellows 228.
Supported by a collapsible container, such as or the like, or other device capable of injecting air when compressed. As shown in FIG. 9A, the needle 224 is a bellows 2
28 in sealed communication. The vial 102 is pushed into the housing 304-5 so that the needle 224 punctures the rubber stopper 112. This arrangement is shown in Figure 9B.

Further pushing of vial 102 into housing 304-5 causes member 232 to
Is pressed to compress the bellows 228, and the air contained in the bellows 228 is compressed by the needle 2
It is sent to the cartridge through 24. At this stage, as shown in FIG. 9C, pressure is applied to the cartridge so as to inject the drug into the person to be injected.
A bellows or other compression device may also be activated by member 232.

As shown in FIGS. 9A-9F, the device 236 is further between a first position inside the housing 304-5 and a second position outside the housing or in a second position in the infused state. And a pushing member 226 for displacing the injection needle 130-5. In the preferred embodiment, the end 130-5 of the injection needle is 5 out of the housing 304-5.
It can extend ~ 12 millimeters. In this particular embodiment, injection needle 130
Is preferably a "U" type needle having a second end 250 configured to pierce the seal member 230. The seal member 230 can include a pierceable material such as butyl rubber to maintain liquid on top of the housing 304.
When the user pushes the pushing member 226 into the housing 304, D of FIG.
As shown in, first, the first end of the injection needle 130 penetrates into the skin of the injection target human. Further pushing of the pushing member 226 into the housing 304 causes the second end 250 of the injection needle 130-5 to pierce the sealing member 230, thereby allowing the reliquefied drug to move from the cartridge to the person to be injected. You will be able to. This is shown at E in FIG. Pushing the pushing member 226 into the housing 304-5 compresses the spring so that releasing the pushing member 226 returns the member to its original position. That is, the injection needle 130-5 is shown in FIG.
As shown in F of FIG. 7, the first position is inside the housing 304-5. This embodiment may further include a locking mechanism similar to the mechanism disclosed in FIGS. Since the injection needle is locked inside the housing 304-5, the device 236 can be safely discarded.

18A-18C show an injection device according to a preferred alternative embodiment of the present invention.
Specifically, drug delivery device 400 includes a straight needle 402 having a lancet 404 disposed at a first end. The cavity 405 of the wall membrane 406 contains the pressurized liquid drug. The straight needle 402 includes a side hole 407 located on the shaft. The second end 408 of the straight needle is blocked. During operation, A, A- in FIG.
1, the member 4 toward the housing 412 as shown in B and B-1 of FIG.
Moving 10 forward moves displacement needle 402 from a first position in housing 412 to a second position outside the housing, resulting in needle 402 penetrating the user's skin. Continuing to push the member 410 toward the housing after the lancet 404 has penetrated the tissue of the user, the side holes 407 fluidly communicate with the cavities 405 of the wall membrane 406 to allow the pressurized drug to flow. A path is formed that flows into the user's tissue. A straight needle pierces the wall membrane 406 in two places. When the hand is released from the member 410 as shown in FIG. 18C, the injection needle retracts inside the housing 412.

Specifically, referring to FIG. 18A-1, the three-part ring structure shown in FIG. 18A, including member 414, latch 416, gap 418 and spring 419, provides an interlock system. . Members 410, 414, latch 416, gap 41
This safety mechanism, including 8 and spring 419, provides drug delivery device 400 after first use.
Provides an interlock that prevents reuse of the needle and exposure of the needle 402. When the member 410 is pushed in, the mating ridges 413A and 413B are mated. The ridge is angled on one side to allow the ridge 413B to pass under 413A when the member 410 is pushed into the housing 412. The member 4 is driven by the force of the spring 419.
The ridges press on each other as the 10 moves away from the housing 412. The ridge interfaces at a right angle to the direction of movement of member 410, so that member and needle 402
Acts to keep the robot from moving further. This mechanism ensures that the device 400 is not reused.

19A-F show cut-away views of a preferred alternative embodiment of a system that allows for reliquefaction of drug and subsequent transfer to a drug delivery device in accordance with the present invention. Once in solution, the drug can be delivered to the user, eg, by direct injection as shown in FIG. 11, or to a drug delivery device, such as a drug infusion pump, needleless injector, or the like. The system includes a vial 420 containing a predetermined volume of drug and a vial 422 containing a volume of diluent. The use of standard vials facilitates the use of drug delivery devices by different drug suppliers.

An air source 424 can be included for delivering the drug. The use of pressure becomes more important for higher viscosity drugs. As shown in FIG. 19A, the source of pressurized air may vary, including compressed air source 426, chemical gas generator 428, standard syringe 430 and collapsible volume containers such as bellows container 432. included. However, it is not limited to these. The air source supplies the diluent container as a driving force to move the diluent solution 434 to the standard lyophilized drug vial 420. After reliquefaction, the liquid drug is transferred to the drug delivery system via an air separator, such as hydrophilic membrane 436. Note that spike 438 of diluent vial 422 and spike 440 of drug vial 420 each have two paths. The spikes 438 have a first path for compressed air to enter the diluent vial 422 and a second path for the pressurized diluent 434 to fluidly communicate with the drug vial 420. .. The spike 440 has a first path for pressurized diluent to enter the drug vial 420 and a second path for supplying the drug solution to the drug delivery device. As discussed above, it is also contemplated to connect other drug delivery devices to this system to receive the drug solution.

Referring to FIG. 19B, the air source is a compressed air canister 426. Compressed air canisters are generally a standard addition to household drug delivery devices. The user attaches the compressed air canister 426 to the drug delivery system 450 and pierces the seal 452 on the compressed air canister. The path 453 allows the air canister to be in fluid communication with the diluent vial 422. Air is expelled from the compressed air canister 426 and introduced into the diluent vial 422, which moves the diluent solution 434 via the path 455 to the drug vial 420. Once reliquefaction is complete, the liquid drug is ready for transfer. In this and other embodiments, the concentration of reliquefied drug can be controlled by varying the amount of diluent transferred to reliquefy the drug. Hydrophilic film 43 on drug supply route
6 minimizes, and preferably prevents, gas transfer to the drug delivery device.

FIG. 19C shows a chemical gas generator 428 used in this particular embodiment as a source of air to supply pressurized diluent 434 to a lyophilized drug vial.
Chemical gas generator 428 generally includes a chemical compartment 456 containing two types of materials 458, 460. The two materials 458, 460 can be two liquids that are separated during storage or liquid and solid pallets 460. Note that the materials used in chemical compartment 456 and the reactions that occur during mixing of the materials are safe and biocompatible. Depressing member 462 of chemical compartment 456 causes the two materials 458 to be stored during storage.
The seal 464, such as an aluminum foil, that had separated 460 is broken. The two types of materials are in fluid communication with each other and react with each other to generate a gas such as carbon dioxide. Chemical gas generator 428 further includes a gas compartment 466, which is generally an air reservoir having a flexible enclosure 468. The carbon dioxide generated by the reaction in the chemical compartment 456 enters the gas compartment 466 and is contained within the flexible layer 468 forming the gas compartment. Movement of the flexible layers 470, 472 forces air or carbon dioxide through the air path 423 into the diluent vial 422. Note that the gas compartment 466 has a bilayer 470, 472 that includes a flexible containment area. The two layers 470, 472 provide safety as air or gas generated as a result of a reaction in the chemical compartment can be accommodated between the flexible enclosures 468 of the gas compartment 466 in the event of a leak. provide. Further, the gas compartment 466 is evacuated using a gas leak path or a bent port 474. Air expelled from the chemical gas generator 428 enters diluent vial 422 via path 423, which moves diluent solution 434 via path 425 to drug vial 420. Once the reliquefaction is complete, the drug is ready for use and the drug is transferred to a drug delivery system such as that described with respect to Figure 19B.

Referring to FIG. 19D, the air source used in this particular embodiment to deliver the pressurized diluent is a standard syringe 430 or reservoir. The syringe 430 is locked at the end of the moving position. Plunger shaft 48
When pressure is applied to zero, air from syringe 430 is forced into the contents of diluent vial 422 through needle 482 and needle 434, which are in fluid communication with member 484. The pressurized diluent 434 is then delivered via member 484 to the drug compartment or drug vial 420, which mixes with the lyophilized drug to provide a reliquefied drug. At this stage the drug
Ready for pressurized injection or delivery to the user. In an alternative embodiment, a lever can be included to reduce the force required to push the plunger member 480. The lever increases the displacement of the pressurized air and thus in this case the supply to the diluent container, injects the drug solution as shown in FIG. 19D or transfers it to the drug supply device. You can The cross section is, for example, FIG.
Same as shown and described for the other needle assemblies shown at 5, 16 and 32.

Referring to FIG. 19E, the air source used in this particular embodiment to deliver the pressurized diluent to the lyophilized drug is a collapsible volume container, such as bellows container 432. is there. Check valve 488 or one way valve is used for bellows container 432
Ensures that the flow from is unidirectional, ie no drug or diluent enters the bellows. The check valve 488 includes a tubular member 490 adapted to supply a gas, such as air, to the diluent vial 422. The elastic nature of the bellows is suppressed by a check valve 480 that does not allow air to enter the bellows and thus allows the bellows to re-expand after it has been compressed and air has been forced out. Once the bellows is compressed, the air contained in bellows 432 is forced through needle 438 and path 491 into diluent vial 422, exerting pressure on the contents of the diluent vial. Diluent solution 434 is loaded with drug vial 42 under pressure.
0, where the drug is reliquefied, which can be delivered by infusion as previously described or to the drug delivery device described and shown with respect to the embodiment of FIG. 19A.

Referring to FIG. 19F, the air source used in this particular embodiment to deliver the pressurized diluent is cylinder 490. This embodiment is D of FIG.
Similar to the embodiment including the standard syringe described with respect to. Depress plunger 492 to compress the air in cylinder 490. Air is driven to the diluent vial 422 through a path 494 that fluidly connects the cylinder and the diluent vial. The pressurized diluent in diluent vial 422 is then transferred to vial 420 and mixed with the drug. The pressurized drug solution at this stage is ready for delivery. This includes delivery to the drug delivery device described with respect to the embodiment of FIG. 19A, or is infused as shown in the embodiment of the invention with the straight needle assembly shown and described in FIG.

Reference is made to FIGS. An alternative embodiment 498 of the drug delivery system according to the present invention includes a standard vial 500 containing liquid drug 502. A volume of gas contained in the air chamber 504, such as air, is stored in the standard liquid drug vial 5.
00, a compressed air is created above the liquid drug, which allows the liquid drug to be pressurized. This usage depends on the position of the vial 500. That is, liquid drug delivery is performed when the standard vial 500 is in the vertical position. Further, the hydrophilic membrane minimizes, and preferably prevents, the introduction of extra air into the user's tissue.

In use, as shown in FIG. 20A, a standard vial 50 containing a liquid drug 502.
0 is inserted into the drug delivery device 498 according to the present invention. An air chamber 504 is provided,
The air chamber is in fluid communication with the drug vial by inserting the drug vial 500 and piercing the vial seal 506. Once inserted, the lip 505A of the standard vial 500 is locked in place by a pair of arms 505 having inwardly projecting ridges 507. This injector system is the straight needle 402 embodiment disclosed in FIGS. 18A-18C. When the air in the air chamber is introduced into the standard drug vial 500, the liquid drug is pressurized, and FIG.
Ready to infuse using the injector system described with respect to AC. After injection into the user's tissue, the needle automatically retracts. The drug supply device 498 is then discarded.

Referring to FIG. 21, a preferred alternative embodiment 510 of a drug delivery system using standard vials 500 containing a drug is disclosed. The drug delivery device 510 includes a plunger 512. In order to reduce the force required to insert the standard vial 500 into the drug delivery device 510, in an alternative embodiment the drug delivery system 510 has a compact configuration without a plunger. A snap 514 locks the standard vial 500 into place. Spike 51 before moving the vial down
A snap 516 holds the end of the vial with the seal 506 in place to ensure that 8 pierces the seal 506 of the vial 500. When the air is compressed and displaced by the downward movement of the vial 500, the air chamber 52
Air in 0 is supplied to vial 500. Liquid drug under pressure pipe 52
2 is used to feed the injector. The hydrophilic membrane 524 minimizes and preferably blocks gas entry into the user's tissue. The injector system used can be a system similar to that described with respect to FIGS.
The member 410 is moved to displace the injection needle 402.

Referring to FIGS. 22A-22E, there is shown a preferred alternative embodiment 530 of a drug delivery system in accordance with the present invention. This particular embodiment can be used as a reliquefaction system and a drug delivery system, which includes two vials 532,534. First vial containing diluent 533 and lyophilized drug 5
35 is a second vial containing 35. In addition, there is an air supply system for the pressurization system, such as a self-contained air cylinder 533 located between the lyophilized drug vial 534 and the diluent vial 536 and in fluid communication with the diluent vial 532. Air is pumped into the diluent vial 532, which causes diluent 533 from the vial to lyophilize the drug compartment or vial 534.
Sent to. Once reliquefaction is complete, the liquid drug is ready for injection. A hydrophilic membrane is used as an air separator to minimize and preferably prevent the entry of air into the user's tissue. This particular embodiment uses the straight needle 402 injector system described with respect to FIGS. Furthermore, A and B of FIG.
Positioning interlocks such as the mechanism described with respect to are used. Further, in an alternative embodiment, instead of an air cylinder, a standard syringe as shown in D and E of Figure 22 is used as the air source. Embodiments that include a syringe include a check valve located (shown in FIG. 16) at the air intake between the syringe and the manifold. The drug delivery system of the present invention is used to deliver a precise volume of drug solution. Various methods can be used to deliver a predetermined volume of drug. In the first embodiment, the dose is controlled by changing the height of the outlet spike 535 in the liquid drug vial 537 as shown in FIG. 23A. That is, the higher the spike, the smaller the amount of drug that moves out of vial 537. The spike is adjusted by a screw 539 over which the spike rotates or slides sealingly. This embodiment can be used to transfer or infuse drug solutions. Another preferred embodiment that enhances the accuracy of the volume of drug delivered uses the amount of drug remaining as a parameter to indicate the volume delivered. One way to control the volume of drug solution delivered is to use the assembly shown in Figure 23B. After the drug is in solution in vial 102, piston 555 allows the solution to be drawn into cavity 541. Cavity 541 has a display thereon to assist the user in determining the appropriate amount. That is, stop the piston at the desired height. The drug solution is then delivered from the cavity 541 via a needle to the user or to the drug delivery device. Another embodiment of delivering a precise volume of drug is disclosed with respect to Figures 24A-C and 25. The reliquefaction system, having a vial containing the reliquefied drug, is effectively used as a filling station for removable dispensing devices, such as standard syringes, pen pumps and the like.

Referring to FIGS. 24A-C, a position independent injector system 540 is shown. Drug 545 is reliquefied as described above with respect to previous systems such as the system shown in FIG. 19F. After reliquefying the drug, the precise dose of drug required can be aspirated by a conventional standard syringe 542. The accuracy using this method is about ± 5%. The height of the fluid in the cavity 550 is controlled by adjusting the pressure and geometry of the device 540. The needle is held in place by an elastomeric wall membrane or plug 552. In use, the reconstituted drug is aspirated into the syringe 542 by moving the plunger 548 which moves the stopper 554 upward to allow the syringe 542 to be filled with the liquid drug, and then the syringe 542 is loaded with the drug delivery device 540. Remove from. The accuracy of the volume of liquid drug delivered is determined by the scale on the syringe. The user then injects the drug and disposes of the syringe by one of several potential methods. One way to dispose of the syringe is to attach it to the empty cavity 550 left in the drug delivery device 540. The second method is to lock the needle 547 by locking the syringe with a plastic tube before disposing of the syringe.
System 540 and the procedure used are air free and do not require an air separator. Syringe needle 547 is located in a closed cavity that penetrates wall membrane 544, thus allowing fluid communication between needle 547 and the reliquefied drug. The volume of the leak-free cavity is controlled by the needle 547 under controlled pressurization conditions.
Designed to guarantee the availability of liquid drugs against. Syringe piston 5
The 48 position is fixed under pressure and the dose is manually aspirated from the syringe.

Referring to FIG. 25, there is shown a preferred alternative embodiment of the drug delivery system 540 described in FIGS. The reliquefaction stage is similar to the stage described with respect to FIGS. However, the injector system, including the attachable delivery device, is different. The user dials into the drug delivery device and dials the required dose using a pen pump 560 that includes a dial 562. This dialing process retracts the floating piston which creates an internal pressure that moves upwards to aspirate the reliquefied drug. The trigger 564 releases the preloaded spring to push the floating piston. Therefore, by dialing the dose, a suction into the pen injector is performed. When the indicator 566 indicates that the pump 560 is full, remove the pump from the filling device. Filling and disposal of pumps
After removal, it is performed using a process similar to that described with respect to FIGS.

26A-D are perspective views of a drug delivery system having a drug delivery device 510 according to the present invention. The diluent vial is inserted into cavity 572 and the lyophilized drug vial is inserted into cavity 574. Cavity 576 houses an air pressurization system for delivering a low viscosity drug. The drug delivery system further includes access 578 for receiving a drug delivery device. The drug is delivered therein via needle 580.

27A-C are cutaway views of a preferred embodiment 600 of a transfer system according to the present invention. When pressurized by the air in cavity 603, the liquid drug in vial 602 is transferred to drug delivery device 604 via extension 606. Liquid drug flows from vial 602 through spike 608 and tubing 610 to needle 616 received in drug delivery device 604.

Referring to FIG. 27B, a drug delivery device 604 is attached to the delivery system 600. The filling process is such that the total drug level is at the outlet 60 of the device 604.
4A (shown in phantom in FIG. 26B) is continued. When that happens, the filling process is complete. It should be noted that during the filling process, drug may flow into cylinder 614 if the user stops pushing vial 602 into transfer system 600. This is prevented by making the frictional force around the tube higher than the tube resistance of tube 610 to drug flow. In an alternative embodiment, a one-way valve can be placed at the end of tube 610. Once the drug supply device 604 is filled with liquid drug, the supply device is moved to the transfer system 600.
Remove from. Residual drug in system 600 is protected, needle 616 retracts,
Since it is fixed in the cover 606 as described above regarding the needle lock mechanism,
Re-exposing will not cause harm or trauma.

28A-C are cutaway views showing the operation of another preferred embodiment 630 of a drug delivery system according to the present invention, specifically a position independent injection system. In this embodiment, the injection system 630 is position independent. That is, the position of the injector need not be vertical during the injection process. Referring to FIG. 28A, drug delivery system 630 includes vial 632 containing liquid drug 634. Liquid drug 634
Flow through spike 636 and along tube 644A into cavity 652. The spike contains two paths. One path 642 for supplying pressurized air from chamber 641 into vial 632 and another path 644 for supplying liquid medication to the user via needle 664. Liquid drug exits path 644 and travels along tube 644A located at the lower end of the spike. One-way valve 638 allows liquid drug 634 to be
Ensure one-way flow to 52A. Spring 640 retains piston 656 inside cavity 652. The floating piston 650 moves inside the cavity 652. The floating piston includes a seal 654. Member 66 on needle assembly 664A
There is 0. Member 660 is hingedly connected to member 662. Member 662 has fingers 662A. Before use, the finger 662A has a housing 660A.
In the opening 662B. A notch 65 is provided at the end of the moving position of the piston 656.
There is 8.

The path 642 from the air chamber 641 to the vial 102 pressurizes the vial by supplying air to the vial. Move the vial downwards and the air chamber 64
The air of 1 decreases. As the vial moves downward, member 641A slides sealingly inside the chamber wall, forcing air into the vial. The member 641A prevents air from leaking from the chamber by the seal 641B.

In use, when vial 632 is pushed into device 630, the air in cavity 641 enters vial 632 and pressurizes the liquid drug. This pressurized drug 634 flows through passage 644 and one-way valve 638 to the left of cavity 652. The pressurized air pushes the floating piston 650 to the right of the cavity 652. Floating piston 65
0 moves to the displaced position of piston 656 and thus to the position of notch 658 at the end of the filled position of cavity 652. Therefore, as shown in FIG. 28B,
The cavity 652 is filled with the correct volume of liquid drug and the device 630 is ready for use.

Depressing member 660, as shown with respect to FIG. 28C, causes needle 664 to move downwardly and out of housing 660A to penetrate the user's tissue. Member 662 is hingedly connected to member 660. Depressing 660 causes member 662 to move upward and out of opening 662B.
2A disengages and spring 640 returns to its less compressed state. At this time, spring 6
40 pushes the piston towards the opposite end of cavity 652. This causes the liquid drug in the cavity to move through the path 652A and needle 664 into the user's tissue and the piston 656 is released by the upward movement of member 662. Piston 6
56 moves to the left. The floating piston 650 is under pressure and delivers the liquid drug in the cavity 652 through the injection needle 664 into the body of the user. Note that the position of the floating piston 650 after delivery of liquid drug depends on the loading of the spring 640. The spring 640 remains pre-loaded to prevent the escape of residual drug under pressure. The seal 654 is pushed to the left of the cavity 652 by the pressure of the spring 640 and seals the pressurized residual drug from exiting through the path 652A. Although an injector having a pushing spring 640 has been disclosed, other features can be included in the injector system to provide a position independent injector.

Referring to FIG. 28D, there is shown a cutaway view of spike 636 having fluid drug 634 in fluid flow communication with the injector system. Spike 636
The vial wall membrane 639 is penetrated when the vial 632 is inserted into the cavity 640. The spike acts as a piston 641A, and the inside of the inner wall of the chamber 641 is sealed by the seal 6
41B allows it to move in a sealable and slidable manner. As explained above, the spike can consist of two additional paths, an air intake 642 and a drug outlet 644. When the vial 632 is inserted, pressurized air enters the vial 632 from the air chamber 641 and allows the liquid drug 634 to pass through the flexible tube 644A.
Through to the injector system. The filling process of the injector system of the preferred embodiment is preferably carried out with a pressure gradient of up to 0.3 bar. This is the maximum back pressure expected, including margins for filling at an altitude of 5,500 feet, for example.

29A and B show partial cutaway views of another preferred embodiment 670 of a drug delivery system in accordance with the present invention.

A drug vial 672 containing liquid drug 674 is inserted into cavity 676. The spike 678 supplies air to the liquid drug vial 672 to pressurize the drug 674 and also provides an outlet for supplying liquid drug to the drug supply system 680. The drug transfer system 670 is in fluid communication with a liquid drug vial 672 via a flexible tube 682 and a needle 684. The flexible tube 682 includes
A hydrophobic membrane 686 is located that prevents air from being delivered to the drug delivery system.
This hydrophobic film 686 prevents backflow. The air in the air reservoir 675 provides air for pressurizing the liquid drug 674. Further during the filling process, a latching mechanism 688 secures the vial 672 to the removable supply system 680.

Referring to FIG. 29A-1, an enlarged view of the interface between the drug delivery system 670 and the removable drug delivery device 680 is shown. A hydrophobic film 692 that blocks the flow of the drug after the drug supply device 680 is full is arranged on this boundary surface. Around the needle 684, an elastomer cover 6 for protection from the needle 684.
94 are arranged. The tab 693 is pulled to remove the hydrophobic membrane 692 before using the device 680.

In operation, liquid drug vial 672 is pushed into cavity 676. This compresses the air in air reservoir 675 into liquid drug vial 672. The seal 685 prevents air from leaking out of the cavity 675. Liquid drug 674 is pressurized and delivered through spike outlet 690. When the vial is unlatched from the drug delivery device at the end of the transfer and subsequent transfer process, the residual air in the air reservoir 675 is evacuated through the opening of the latch mechanism 688.

Referring to FIGS. 30A and 30B, a manifold two-piece structure 6 according to the present invention.
96,697 are shown. The manifold may be a biocompatible material such as polycarbonate, acrylic resin, or a gas impermeable membrane 69 welded to the component 696.
8 is a pvc molded product. The two pieces 696, 697 are ultrasonically welded to each other.

Referring to FIGS. 31A-E, there are shown perspective views of a preferred alternative embodiment 700 of a drug delivery system in accordance with the present invention. This particular embodiment can be used with a reliquefaction drug delivery system, and two vials 702 and 704.
including. A first vial containing a diluent and a second vial containing a drug that needs to be reliquefied. Further, there is a pressurization system such as a self-contained cylinder 706 in fluid communication with the diluent vial 702. A self-contained pressure system such as cylinder 706 is located between the lyophilized drug vial and the diluent vial. A plunger 708 is slidably received in the cylinder 706 to provide the air pressure necessary to achieve drug transfer. Air is forced into the diluent vial and pushes the diluent from the diluent vial into the lyophilized drug compartment or vial 704. As previously discussed, hydrophilic membranes are used as air separators to minimize and preferably prevent entry of air into the user's tissue. When using,
The diluent vial is inserted into the drug delivery system 700, followed by the drug vial. Press the plunger 708 downward to pressurize the air in the cylinder 706,
Pressurized air is supplied to diluent vial 702. The diluent solution is pressurized and the pressurized diluent solution is supplied to drug vial 704 to reliquefy the drug. Pushing on the knob mechanism 710 displaces the injection needle used to inject the reliquefied drug into the user's tissue. Depressing the knob mechanism and subsequent infusion is similar to that described above for the straight needle assembly shown in FIG. 18 or the U-shaped needle shown in FIGS. 11, 13-17.

Referring to FIGS. 31F and 31G, two preferred embodiments 711, 713 are shown in which the orientation of the device is visually indicated. Vertical indicators 711, 71
The three are located on top of the plunger 708, but their position can be changed to provide the appropriate visual indication. In the first embodiment of the vertical indicator 711, a metal ball 714 rests on a curved surface with a visual indicator or scale 712 on it. Ball 714 is a transparent casing 712A.
It is contained within. Positioning the ball 714 in the center of the scale is an indication that the orientation is vertical. In the second embodiment of the vertical indicator 713, air bubbles 71 in the liquid 718 contained in the transparent housing 718A.
6 is used as a visual indicator of the orientation to the scale 719. The location of the bubble 716 in the center of the scale is an indication that the orientation is vertical.

32A-E, there is shown a perspective view of another alternative embodiment 720 of a drug delivery system, specifically a reliquefaction / infusion system, in accordance with the present invention. In this embodiment, reliquefaction of the drug is performed by mixing the diluent solution with the drug. This particular embodiment does not require a separate pressurizing system for the diluent and can only be used with low viscosity drugs. In use, knob 730 is moved counterclockwise to initiate the drug reliquefaction process. This opens a pathway to connect the diluent to the drug. Knob 730 is rotated from the unused position (indicated when notches A and B are aligned) to the usable position indicated by the alignment of notches B and C. At this point the knob 730 can be pushed in to inject the solution. The internal pressure and gravity of the diluent vial transfers the diluent to the vial containing the drug. Further movement of the knob or dial 730 actuates the user's tissue and interface lower injection needle to deliver reliquefied drug. The injection assembly is again similar to the embodiment shown in FIGS. 11, 13-17.

33A-I, there is shown a cutaway view of a preferred embodiment of a drug delivery system, highlighting interlocks arranged to provide a secure system. 33A and B, the interlocks required during the shelf life of the drug delivery device 750 are shown. The end of the cylinder 752 has a deformable lip 766 that extends outwardly and mates with the wall 758, which is sufficiently flexible to bend under the pressure of the wall 758 when the vial is inserted into the assembly. There must be. During the storage period, cylinder 752 is secured by latch 754 and mating lip 756. This fit prevents the movable cylinder 752 from moving vertically before use. Cylinder 752 provides pressurized air to drug delivery system 750, as previously described. Downward movement of cylinder 752 is minimized and preferably prevented by retaining latches 754 and 756 in wall 758. The upward movement of cylinder 752 is latched 754.
Blocked by.

Reference is made to FIG. 33C. The next step is to add vials 760 and 762 to device 75.
Including to insert 0. Only after inserting both vials 760, 762 can cylinder 752 be pushed vertically. The insertion of the vial pushes the lip 766 inward, which creates a gap between the lip and the wall 758 and thus allows the cylinder 752 to move downward. In addition, a latch 754 secures the vial in the device 750.

Referring to FIGS. 33D and 33E, interlocks that play a role when the cylinder 752 is pushed are shown. The cylinder 752 is pushed downwards to the end of its travel position and locked by the mating of the lip 766 and the interlock element 768.
Again, as described above before use, the lip 766 again moves downwardly and is captured on the element 768 to a radially spread position which prevents the cylinder from moving upwards again. Locking element 768 holds the cylinder in a bottomed position. Element 768 is formed as part of wall 758.

In the area where the drug solution is injected, there is a pushing member that moves in a direction perpendicular to the direction in which the cylinder moves. Prior to use, balls 772 are located inside the housing to prevent member 776 from falling. When the cylinder is fully depressed, the lip 766 pushes the member 770, which allows the ball 772 to fall into the groove 774, allowing movement of the pushing member 776 only when the device is in the vertical orientation.

Reference is made to F and G in FIG. Various interlocking elements ensure safe use of the drug delivery system during the infusion process. Depressing the pushing member 776, which is only actuable when the drug delivery system 750 is in the vertical orientation, causes corner 7
78 unfolds the latch 780, which allows the member 770 to push the ball 772 upwards. Note that the pushing member 776 has already been pushed to expose the needle 782.

Referring to H and I of FIG. 33, the interlock during the disposal phase of the drug delivery device after the infusion phase is shown. The pushing member 776 is released by the action of a spring 777 that pushes the member 776. Movement of ball 772 is limited by the body of member 776 so that when member 776 is released, rear shell latch 78
When assisted by the pressure exerted by 0, the ball 772 has a groove 77
You'll be able to go back into 4. This locks the pushing member 776 in place, thereby preventing the drug delivery device 750 from being used again.

Referring to FIGS. 34A-D, there is shown a preferred embodiment of a drug delivery device having an end of delivery indicator. As discussed above with respect to the preferred embodiment of the drug delivery system of the present invention, the drug delivery system operates with a pressurized gas, eg, air. Air delivers the drug to the infusion site by pressurizing the drug. The hydrophilic membrane minimizes and preferably blocks the entry of air into the user's body. The hydrophilic membrane is placed on the drug route to the user's tissue. The wet hydrophilic membrane allows the liquid drug to enter the user's tissue, but blocks the passage of air to the user's tissue. The hydrophilic membrane must be wet to ensure the effectiveness of the membrane.
To make the drug delivery device more effective, an additional hydrophobic membrane is placed on the drug pathway. Referring to FIGS. 34A and B, the inlet 800 for supplying liquid drug 802 into cavity 803 has a hydrophobic membrane 806 and a hydrophilic membrane 810 disposed therein. The hydrophobic film 806 allows air to pass but does not allow liquid to pass. Cavity 803
The hydrophilic membrane 810 on the opposite side of the membrane allows liquid drugs to pass through but does not allow gas to pass through. At one end of the hydrophobic membrane 806 is placed a flexible elastomeric diaphragm that acts as an indicator when filled with gas, eg air. This flexible membrane, when filled with air, provides an external indication to indicate the end of the feed. Air is present only when the liquid drug has completed supply. It should be noted that the hydrophilic membrane 810 is located near the injection site as it allows liquid to pass through to the injection site and minimizes or blocks the inflow of gas into the user's tissue. .

FIG. 34D shows a manifold structure that utilizes an end-of-supply indicator 804 incorporated into the manifold. The wall membrane 814 surrounds the cavity containing the liquid drug. Spikes 816 and 818 interface with the elastomeric stopper of the vial containing diluent and drug.

FIG. 35 shows a graph of the delivery profile for a high volume vial with no additional air pressure inside the vial. This profile shows the profile of pressure (mbar) against time (sec). The internal pressure of the original vial is of the order of about 300 mbar, the internal pressure decreasing during the feeding process to about 0 mbar at the end of the feeding process. This is in contrast to the internal pressure of the vial that initially contained about 3 milliliters of air shown with respect to FIG. As a result, there is no residual air pressure in the vial after the supply is complete. The feeding process lasted about 86.4 seconds.

FIG. 36 shows a graph of supply duration and supply pressure against air volume in the vial. Three different profiles are shown. First profile 8
30 indicates the pressure before delivery (mbar), the second profile 832 indicates the residual pressure of the delivery, and the third profile 834 indicates the delivery of 0.95 ml of liquid drug over about 8 seconds.

FIG. 37 is a graph showing the delivery parameters for liquid drug infusion without additional air in the vial. As the drug is delivered, the pressure in the liquid vial drops for about 17 seconds of delivery. These curves show the test results of a delivery process of about 1 gram of liquid drug using a single drug delivery device for the same amount of time.

FIG. 38 shows test results showing the air pressure gradient over the hydrophilic membrane used to minimize and preferably prevent gas, eg air, from entering the user's tissue. The test results prove the safety of the membrane and ensure that it can withstand a pressure of the order of 2,700 mbar for about 6 minutes.

FIG. 39 is a graph showing the performance of the drug supply device according to the present invention. Three delivery profiles 840, 842, 844 (ml) versus time (seconds) are shown for the reliquefied lyophilized drug delivery system. In order to minimize and preferably prevent the inflow of gas into the tissue of the user, this system uses a pore size of 0.
． Includes 45 micron hydrophilic membrane. This particular pore size membrane provides a suitable particle filter and further allows the drug to be delivered to the user's tissue in the shortest time.

FIG. 40 is a flow chart illustrating a method for supplying a freeze-dried drug according to the present invention.
The method includes the step 899 of inserting the drug container and diluent container into the drug delivery device. Further according to step 900, the method includes the step of activating a source of pressurized air, followed by the step 902 of pressurizing the diluent solution in the diluent vial. As discussed with respect to FIGS. 19A-F, the pressurization step can be provided by a subsystem including a compressed air supply, a chemical gas generator, a collapsible volumetric air supply, a standard syringe or a cylinder. However, the subsystem is not limited to these.

The method further comprises supplying 904 the pressurized diluent solution to the lyophilized drug vial. According to step 906, the lyophilized drug is reliquefied as a result of mixing the lyophilized drug with the diluent. The method further includes delivering 908 the liquid drug to the injector system or transferring the liquid drug to the removable delivery device 908. The liquid drug is then injected into the user's tissue according to step 910. The injection needle is then moved to a safe storage position according to step 912.

FIG. 41 is a flow chart illustrating a method for supplying a liquid medicine according to the present invention. The method includes inserting 913 a drug container, such as a vial, into the drug delivery system. Further according to step 914, the method includes activating a source of pressurized air for the low viscosity drug. Note that pressurization may not be necessary for high viscosity drugs. The method then includes step 916 of pressurizing the standard drug vial. According to step 918, the pressurized liquid drug is transferred to a drug delivery system, such as an infusion system, a removable delivery device. The liquid drug is then injected into the tissue of the user according to step 920. The method further includes withdrawing 922 the injector to a safe storage position.

FIG. 42 is a front sectional view of another embodiment 928 of the present invention. This embodiment includes a first recess 932 for receiving a drug container 933 having a drug therein, and a second recess 93 for receiving a diluent container 935 having a diluent therein.
4 includes housing 930. The diluent container 935 has an upper lip 937 that receives and locks into a snap 939 in the second recess 934. The housing 930 further includes a plunger 936 sealingly and slidably engaged in a third recess 938 containing air. The plunger has a catch 941 extending radially inward and in locking engagement with a locking collar 943 of the housing 930.
The third recess 938 communicates with the second recess by the first path 940. The diluent container is slidably received on the first spike 942. The drug container is
Received slidably on the second spike 944. The first spike 942 is
The second passage 946 fluidly communicates with the second spike 944. The second spike further includes a third path 948 that fluidly communicates the drug container with the measurement chamber 950. A check valve 947 is arranged between the measuring chamber 950 and the third path 948. The check valve 947 is in the form of a rubber flap covering the inlet of the third passage 948 entering the measuring chamber 950, which valve opens at pressure from the third passage and exits from the third passage. Allows fluid flow to the measurement chamber but closes when pressure is applied in the opposite direction and does not allow fluid flow from the measurement chamber to the third path. There is a fourth path 949 that allows the liquid to flow between the measurement chamber 950 and the supply chamber 951.

The measurement chamber 950 includes a piston 95 fixed to one end of a threaded rod 954.
Including 2. The piston 952 is slidably engaged in the measuring chamber 950.
The second end of threaded rod 954 is threadably received in a pair of jaws 956 having mating threads for receiving the second end of the threaded rod. The jaw portion 956 is a part of the elastic member 958. Member 958 has an axial spring 960.
Receive in it. Spring 960 is aligned with its longitudinal axis parallel to the longitudinal axis of member 958. Spring 960 leans against the rear end of threaded rod 952. The member 958 is retained within the sleeve 962 in the housing 930. The sleeve 962 has a radial recess 964 on its inner surface. The radial recess 964 is sized to receive the jaw 956 during use. The member 958 is matingly received in the outer knob in such a manner that the outer knob 966 can control the radial rotation of the member in use. The knob has an inner surface 968 that presses against the sleeve 962.

The housing 930 further includes an activation assembly 97, shown in detail in FIGS.
Including 0. The activation assembly 970 includes a button / path 97 within the housing 930.
1 includes a button 972 slidably engaged therein. Button 972 is outer surface 975
, And an annular inner extension 977 having a diameter less than the diameter of the outer surface. Annular extension 977 has a cylindrical recess 978 therein. The annular extension 977 further includes an annular slit 980 forming a pair of annular protrusions, an inner annular protrusion 981 and an outer annular protrusion 982. Inner annular protrusion 981 frictionally receives locking sleeve 984. The locking sleeve 984 has an outwardly extending annular lip 986 having a sloping outer surface that slides over and mates with a ridge 988 secured to the wall of the activation chamber 976. The ridge 988 has a beveled surface designed to allow the annular lip to slide over it, but the ridge further provides a flattened mating abutment with the flat lower surface 991 of the annular lip 986 during use. It has an end surface 989.

Button 972 has a supply needle 973 mounted therein. Supply needle 97
3 and the button 972 are elastically attached to the housing 930 by an activation spring 974. The needle 973 is axially located midway and has a lateral opening 990 designed to align with the supply chamber 951 during use, as will be described later.

In use, the drug container 933 is inserted into the first recess 932 and pushed down until the bottom of the drug container is flush with the outer surface of the housing 930, as shown in FIG. This will break the seal on the drug container 933 and allow the second spike 944 to
Is received in the drug container. Insert the diluent container 935 into the second recess 934 until the upper lip 937 of the diluent container 935 snaps 939 into place. In this position, the first spike 942 is received inside the diluent container 935. The plunger 936 is then fully depressed until the catch 941 engages the collar 943 of the housing 930 in a locking manner. Moving the plunger 936 downward causes air in the third recess to move through the first path 940 and into the diluent container 935, as shown in FIG. This causes the diluent in the diluent container 935 to flow to the drug container 933 through the second path 946. When the diluent is introduced into the drug container, as shown in FIG. 43, the administrable drug solution (or drug dispersion) 9
75 are produced.

To determine the proper and accurate dose, the user rotates knob 966 (as indicated by the arrow in FIG. 44). As knob 966 rotates, it also causes jaw 956 to rotate, which causes threaded rod 954 and piston 952 to be retracted toward the knob. As a result, the drug dispersion liquid 975 is sucked into the measurement chamber 950 as shown in FIG. Once the knob 966 is rotated to the proper position on the housing that indicates the desired dose, the user can
2 is pushed forward toward the inside of the housing 930. This makes the jaw 95
6 can be moved into the radial recess 964 of sleeve 962, releasing the threaded engagement and allowing spring 960 to push threaded rod 954 and piston 952 forward. As a result, the drug solution 975 becomes A in FIG.
Flows from the measurement chamber 950 to the supply chamber 951 as shown in FIG.

At this time, the user presses the surface of the housing opposite to the button 972 against the surface of the desired area of the skin. The user is free to press button 972, which causes needle 973 to move through the opening in housing 930 and the surface of the skin and into the skin. When the needle is moved to a suitable position inside or under the skin,
The needle opening 990 is aligned with the supply chamber 951 as shown at 6B. This allows the drug solution 975 to flow from the supply chamber 951 through the needle 973 to the user. Further pressing of button 972 will drive locking sleeve 984 forward toward the interior of the housing. This causes the ramp 986 of the lip 986 of the locking sleeve 984 to snap over the ridge 988. When the button is fully depressed, the annular recess 978 is fully received within the locking sleeve 984, with the bottom of the annular recess contacting the end of the locking sleeve as shown in Figure 46B.

Once the drug solution 975 has been dispensed, the user stops pressing the button 972, which causes the needle 973 to be retracted by the spring 974 into the housing 930. Spring 974, along with its recessed boss 977 and annular recess 988, also causes button 972 to move away from housing 930. The locking sleeve 984 is then held in place by the one-way snap relationship between the lip 986 and the ridge 988 so that the recessed boss 977 slides out of the sleeve. When button 972 returns to its original position, annular recess 97
8 is no longer in contact with the lock sleeve 984. Then, the inner protrusion 981
Moves away from the outer protrusion 982 and bends radially inward as shown in FIG. 46C. Therefore, even if the user pushes the button 972 again, the inner protrusion 98
1 hits the rear end of the locking sleeve 984 and the button 972 does not enter the housing 939 any further. Since the supply needle 973 is attached to the button 972, the supply needle also cannot move from its retracted position into the housing 930. This prevents reuse of the device and prevents accidental needle sticks by the user or caregiver. This helps avoid a number of diseases and viral contaminations, for example diseases and viral contaminations that spread through contact with body fluids.

Further, it should be understood that the present invention can be used to deliver a number of drugs. As used herein, the term “drug” includes peptides or proteins (and their mimetics), antigens, vaccines, hormones, analgesics, antimigraine agents, anticoagulants, central nervous system diseases and conditions. Drugs for treatment, opiate antagonists, immunosuppressants, drugs used in AIDS treatment, chelating agents, antianginal drugs, chemotherapeutic agents, sedatives, antitumor agents, prostaglandins, antidiuretics, And DNA or DNA / RNA molecules that support gene therapy. However, it is not limited to these.

Representative drugs include insulin, calcitonin, calcitonin gene regulatory protein, atrial natriuretic protein, colony-stimulating factor, beta-serone, erythropoietin (EPO), interferons such as α, β, γ interferon. , Somatropin, somatotropin, somastostatin, insulin-like growth factor (somatomedin), luteinizing hormone-releasing hormone (LHRH), tissue plasminogen activator (TPA), growth hormone-releasing hormone (GHRH), oxytocin, estradiol, growth hormone, acetic acid Leuprolide, VIII
A factor, an interleukin such as interleukin 2, a peptide such as an analogue or antagonist thereof such as IL-1ra, a protein or a hormone (or a mimetic or analogue thereof); fentanyl, sufentanil, butorphanol,
Buprenorphine, levorphanol, morphine, hydromorphone, hydrocodone, oxymorphone, methadone, lidocaine, bupivacaine, diclofenac,
Analgesics such as naproxen, paveline, and their analogs; antimigraine agents such as sumatriptan, ergot alkaloids, and their analogs; heparin, hirudin,
Anticoagulants such as their analogs; scopolamine, ondansetron, domperidone, metoclopramide, antiemetics such as their analogs; diltiazem, clonidine, nifedipine, verapamil, isosorbide-5-monotritate, organic nitrates, heart Drugs used in the treatment of diseases, cardiovascular drugs such as their analogs, antihypertensives and vasodilators; sedatives such as benzodiazepines, phenothiazines, their analogs; chelating agents such as defloxanun, their analogs; Antidiuretics such as desmopressin, vasopressin, their analogs; fluorouracil,
Antianginal agents such as bleomycin, analogs thereof; antitumor agents such as fluorouracil, bleomycin, analogs thereof; prostaglandins and analogs; vincristine, analogs, attention deficit treatment, methylpheni Dating,
Chemotherapeutic agents such as fluvoxamine, bisoprolol, tacrolimus, tacrolimus, cyclosporine are included.

While the invention has been shown and described with particular reference to preferred embodiments thereof, the forms and details of the invention can be changed without departing from the spirit and scope of the invention as defined by the appended claims. Those skilled in the art will appreciate that various changes can be made. For example, some position independent features can be used with reliquefaction coupling systems, transfer systems or infusion systems. Similarly, the interlock feature can be used with any of the systems described above.

[Brief description of drawings]

[Figure 1]   1A to 1F are diagrams showing the operation of the preferred embodiment of the drug supply device.

2A and 2B are views of FIG. 1 taken along line 2A-2A, 2B-2B of FIG. 1F.
FIG. 7 is a cutaway view of the drug supply device shown in FIGS.

3A-3D are cross-sectional views of the internal components of the drug delivery device of FIGS. 1A-E and 2A-B during administration of a reliquefied drug.

[Figure 4]   4A-4O are diagrams illustrating the operation of the preferred embodiment of the drug delivery device.

[Figure 5]   5A-5C are perspective views of a preferred embodiment of the drug delivery device.

6A to 6C are views showing the operation of the drug supply device substantially similar to the device shown in FIGS. 5A to 5C.

7A-C are partial perspective views of the drug delivery device of FIGS. 5A-C and 6A-C showing drug infusion.

8A to 8F are views showing the operation of the drug supply device substantially similar to the devices shown in FIGS. 5A to 5C.

[Figure 9]   9A-F are diagrams illustrating the operation of the preferred embodiment of the drug delivery device.

[Figure 10]   10A and 10B are graphs showing pressure, weight and supply characteristics.

11A-D are cutaway views of an alternative embodiment including a drug container subassembly of a drug delivery device.

12A and 12B are perspective views of the preferred embodiment of the diluent container subassembly shown in FIGS. 11A-11D.

[Fig. 13]   13A and 13B are cutaway views of an alternative embodiment of the drug delivery device.

FIG. 14   FIG. 8 is a cutaway view of another preferred embodiment of a drug delivery device.

FIG. 15   15A and 15B are cutaway views of an alternative embodiment of the drug delivery device.

FIG. 16   FIG. 3 is a cutaway view of the injection device.

FIG. 17   17A-C are cutaway views of an alternative embodiment of a drug delivery device.

18A-18C are cut-away views of an alternative embodiment of the injector system of the drug delivery system.

19A-19F are diagrams illustrating an alternative embodiment of a pressurization system included in a drug delivery system.

20A-C show an alternative embodiment of a drug delivery system using standard vials containing liquid medication.

FIG. 21 illustrates another preferred embodiment of a drug delivery system using standard vials containing liquid medication.

22A-E are cutaway and perspective views of an alternative embodiment of a drug delivery system.

FIG. 23A and B are diagrams showing a preferred alternative embodiment for controlling the dose of a drug.

24A-C are cut-away views of an alternative embodiment of a drug delivery system incorporating a filling device, such as a syringe, for injecting a drug.

FIG. 25: Incorporates a filling device, eg a pen pump, for injecting a liquid drug,
FIG. 8 is a cutaway view of an alternative embodiment of a drug delivery system.

FIG. 26   26A-D are perspective views of a preferred embodiment of the drug delivery system.

FIG. 27   27A-C are cutaway views of a preferred embodiment of the drug delivery system.

28A-C are cutaway views showing the operation of the preferred embodiment of the drug delivery system. 28D is an enlarged cut-away view of a preferred embodiment of a spike that communicates liquid medication with the delivery system of FIGS. 28A-C.

29 A and B of FIG. 29 are partial cutaway views of a preferred embodiment of the drug delivery and delivery system.

30A and 30B show a two-piece manifold based on a drug delivery system.

FIG. 31   31A-G are perspective views of a preferred embodiment of the drug delivery system.

32A-E are perspective views of another preferred embodiment of a drug delivery system.

33A-I are cutaway views showing interlocks incorporated into a drug delivery system.

34A-D are views of a preferred embodiment showing an end-of-delivery indicator for a drug delivery system.

FIG. 35 is a graph showing the delivery profile of a preferred embodiment of the drug delivery system with no additional air volume in the liquid vial.

FIG. 36 is a graph showing delivery duration and delivery pressure for a preferred embodiment of the drug delivery system.

FIG. 37   Figure 7 is a graph showing delivery parameters for injecting drug without additional air volume.

FIG. 38   3 is a graph showing an air pressure gradient on a hydrophilic membrane of a drug supply system.

FIG. 39 is a graph showing a delivery profile over time for a vial system containing about 7.5 ml of air.

FIG. 40   It is a flowchart explaining the supply method of a reliquefied drug.

FIG. 41   It is a flowchart explaining the supply method of a liquid drug.

FIG. 42 is a front cross-sectional view of a preferred embodiment of a liquid drug measurement assembly incorporated into a lyophilizate injection system.

43 is a front cross-sectional view of the preferred embodiment of FIG. 42 with the diluent transferred to the drug container to form the drug solution.

44 is a front cross-sectional view of the preferred embodiment of FIG. 42 with liquid drug aspirated into the measurement chamber.

45A is a cross-sectional view of the preferred embodiment of FIG. 42 with liquid medication emptied from the measurement chamber. 45B is a cross-sectional view of the preferred embodiment of FIG. 42 with the liquid drug completely emptied from the measurement chamber.

FIG. 46A is a second cross-sectional view of FIG. 45 showing the activation assembly before use. 46B is a second cross-sectional view of FIG. 45 showing the activation assembly in use. FIG. 46C is a second cross-sectional view of FIG. 45 showing the activation assembly after use.

[Explanation of symbols]

102 vials 116 cartridges 130 injection needle 166 Diluent 304 housing 933 Liquid drug chamber 935 Diluent room 950 Drug measurement room 952 piston 960 spring 966 Manual control element

─────────────────────────────────────────────────── ─── Continued front page    (81) Designated countries EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, I T, LU, MC, NL, PT, SE, TR), OA (BF , BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, G M, KE, LS, MW, MZ, SD, SL, SZ, TZ , UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, B Z, CA, CH, CN, CO, CR, CU, CZ, DE , DK, DM, DZ, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, I S, JP, KE, KG, KP, KR, KZ, LC, LK , LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NO, NZ, PL, P T, RO, RU, SD, SE, SG, SI, SK, SL , TJ, TM, TR, TT, TZ, UA, UG, US, UZ, VN, YU, ZA, ZW (72) Inventor Tusarus, Islay             United States 01776-1069 Massachusetts             Rose Way, Sudbury, Usets               17 F term (reference) 4C066 BB01 CC01 DD13 FF05 GG03                       HH24

Claims (36)

[Claims] 1. A drug delivery system for administering a liquid drug to a patient (human or non-human), which is connected to or adapted to be connected to a liquid drug chamber (933) and which has a dose output port and a supply route. Liquid drug intake (9
48), said dose output port being adapted to connect to a drug administration element (973), such as a needle or an infusion tube for introducing liquid drug into the patient's body, or said drug administration element (973) And a drug measuring system including a drug measuring chamber (950) connected to the supply path between the liquid drug intake port and the administration output port, and the drug measuring chamber. A volume control mechanism that allows a controlled volume of liquid drug corresponding to the volume to be received from the liquid drug intake during use by being progressively adjusted over a range. Means for delivering a variable volume of the liquid drug from the drug measurement chamber (950) to the dosing output port. 2. A liquid drug is prevented from flowing back from the drug measuring chamber (950) to a liquid drug intake port and / or the drug measuring chamber (950) is discharged from an administration output port.
2. The drug delivery system of claim 1, wherein the delivery path comprises one or more valves (947; 990) that prevent fluid from being drawn into the. 3. The delivery means, for example, is characterized in that the volume control mechanism and the delivery means are separated from each other or can be separated from each other so as not to reverse the operation of the volume control mechanism. Item 1 or claim 2
The drug supply system according to. 4. The volume control mechanism according to any one of claims 1 to 3, wherein the volume control mechanism includes a manual control element (966) capable of performing the adjustment to a desired volume of the drug measurement chamber (950). The drug supply system according to 1 above. 5. The drug measurement chamber (950) is located between a cylinder (92) and a cylinder (952) that is included in the volume control mechanism and is axially relatively movable to adjust the volume. The drug supply system according to claim 1, wherein the drug supply system is provided. 6. The delivery means is adapted to deliver the liquid drug to the administration output port by returning the drug measurement chamber (950) to its original state. 5. The drug supply system according to any one of 5 above. 7. The drug delivery system of claim 6, wherein the delivery means includes a spring (960). 8. The drug of claim 7, wherein the spring (960) is arranged to be preloaded by the operation of the volume control mechanism when adjusting the volume of the measurement chamber. Supply system. 9. A cylinder and a piston (9) included in the volume control mechanism, which are relatively movable in the axial direction to adjust the volume of the drug measuring chamber.
52) and the volumetric control mechanism is positioned between the volumetric control mechanism and the rotatable manual control element () connected to the piston (952) via a threaded engagement or other progressive cam engagement. 966), with the result that said manual control element (96
When 6) is rotated, the drug measuring chamber can be expanded by linearly pulling out the piston from the cylinder, and a separation mechanism for separating the piston (952) from the manual control element (966) is provided. Comprising the piston (952)
3. A delivery device according to claim 1 or 2, characterized in that said feeding means comprises a biasing device (960) or a pressure device for advancing said piston (952) when is separated from said manual control element (966). The drug supply system described. 10. The threaded engagement between the manual control element (966) and the piston (952) includes a male threaded portion (954) and a split female threaded portion (956), the separation 10. The drug delivery system of claim 9, wherein the mechanism is operable to disengage the male threaded portion (954) from the split female thread (956). 11. The drug of claim 9, wherein the cam engagement exists between the rotatable manual control element and the piston, and a separation mechanism operates to release the cam. Supply system. 12. The separation mechanism is operable by moving the manual control element (966) in a movement direction different from the direction used to adjust the volume of the measurement chamber. The drug supply system according to any one of claims 3 and 9 to 11. 13. A drug delivery system according to claim 12, characterized in that the separating mechanism is activated by pressing the manual control element (966). 14. The drug delivery system according to claim 3, wherein the separation mechanism includes a cam mechanism for releasing an element of the volume control mechanism. 15. The delivery means as claimed in claim 9, wherein the delivery means comprises an axially actuable spring (960) which feeds the piston axially forward into the cylinder. The drug supply system described. 16. A diluent inlet connected to or adapted to be connected to a liquid diluent chamber (935), and a liquid drug chamber (93) from said diluent chamber (935).
16. A drug as claimed in any one of claims 1 to 15 further comprising a diluent path communicating from the diluent intake to the liquid drug intake to carry the diluent to 3). Supply system. 17. Inlet according to any one of the preceding claims, characterized in that the intake is perforated by perforating elements (944, 942) for perforating the perforable wall of the chamber to which it is connected. The drug supply system described. 18. A method for measuring the volume of a liquid drug by the operation of the drug supply system according to any one of claims 1 to 17. 19. A method of delivering or administering a volume of a liquid drug comprising the operation of a drug delivery system according to any one of claims 1 to 17. 20. A drug measuring device for a drug supply system according to any one of claims 1 to 18. 21. A liquid drug volume measuring device, comprising:   A first chamber containing a liquid drug;   A measurement chamber in communication with the first chamber,   A volume measuring device comprising a measuring assembly. 22. A measurement assembly comprising: a piston slidably received in the measurement chamber; a member in radial communication with the piston; and a member in radial communication with the member, the shaft being in axial communication with the member. And a knob attached to the measurement chamber in a direction, the movement of the knob causes a piston to move along the measurement chamber, whereby the liquid drug is sucked into the measurement chamber. The volume measuring device according to claim 21. 23. The volumetric device of claim 22, wherein the piston includes a piston head and a threaded rod. 24. The volume measuring device according to claim 23, wherein the piston head is made of rubber. 25. The member has internal threads axially along a portion of the length of the member and / or the member is preloaded radially outward. 22. The volume measuring device according to 22. 26. The measurement assembly further comprises a sleeve having an annular recess within the measurement chamber that slidably receives along a portion of the length of the measurement chamber and slidably receives the member; 23. A volumetric device according to claim 22, comprising: a spring axially mounted along the inner length. 27. The volumetric measurement of claim 26, wherein the member further comprises an annular extension along a portion of the outer surface of the member for engaging a receptacle in the annular recess. apparatus. 28. The volume measuring device according to claim 27, wherein one end of the sleeve is in contact with a wall of the measuring chamber, and the other end of the sleeve is in contact with a knob. 29. An apparatus for supplying a measured volume of drug, comprising a first chamber containing a liquid drug, a measurement chamber in fluid communication with the first chamber, and the measurement. A piston frictionally received in the chamber, a member in radial transmission relationship with the piston and having an annular extension, and slidably and elastically in the measurement chamber in radial transfer relationship with the member A measurement assembly having a knob attached to the piston, an axial spring for providing axial force to the piston and the knob, slidably attached to a portion of the length of the measurement chamber, and the annular shape of the member. The device is provided with a sleeve having a radial concave portion with which the receiving portion of the extension portion engages, and a needle that fluidly communicates with the measurement chamber. When the knob is rotated, the member is piston Engaging in a radial transfer relationship, the piston moves axially along the length of the measuring chamber, whereby the drug solution is aspirated into the measuring chamber and then the knob is moved into the measuring chamber. When pushed inwardly, the annular extension is received in the radial recess of the sleeve, thereby releasing the radial transmission relationship between the member and the piston, and the spring being the piston. Device for delivering a drug characterized in that it moves axially with respect to the liquid drug and flows from the measuring chamber through a needle. 30. The volume measuring device of claim 29, wherein the piston includes a piston head and a threaded lot. 31. The device of claim 30, wherein the piston head is made of rubber. 32. The apparatus of claim 29, wherein the member has an internal axial thread along a portion of the length of the measurement chamber. 33. The device of claim 29, wherein the member is preloaded radially outward. 34. The apparatus of claim 29, wherein one end of the sleeve contacts the wall of the measurement chamber and the other end of the sleeve contacts the knob. 35. A method of measuring the volume of a liquid drug, comprising: providing a first chamber containing a liquid drug; and providing a measurement chamber in fluid communication with the first chamber. A piston slidably received in the measurement chamber, a member in radial transmission relationship with the piston, and slidably axially slid into the measurement chamber in a radial transmission relationship with the member. Providing a measurement assembly with an attached knob, and rotating the knob to set the desired setting to bring the liquid drug to the first position.
A method of measuring the volume of a liquid drug, comprising the steps of: aspirating from the chamber of (1) and placing it in the measurement chamber to reach the measured volume. 36. A method of supplying a measured volume of a liquid drug, the method comprising: providing a first chamber containing the liquid drug; and a measurement chamber in which the first chamber and the liquid are in fluid communication with each other. And a piston slidably received in the measuring chamber, a member in radial communication with the piston and having an annular extension, and an axis in radial communication with the member. Providing a measurement assembly with a knob slidably attached to the measurement chamber, and mounting an axial spring in contact with one end of the piston along the inner length of the member, Providing a sleeve slidably mounted on a portion of the length of the measuring chamber, the sleeve having a radial recess for engaging a receiving portion of an annular extension of the member; Room and Providing a needle in fluid communication with the liquid; preloading the member radially outwardly; rotating the knob to a desired setting to transfer the liquid drug to the first
Suctioning from the chamber into the measuring chamber to reach the measured volume, the knob is pushed axially inward with respect to the measuring chamber, the annular extension being the radial recess of the sleeve. Received by the spring, thereby causing the spring to move axially relative to the piston, causing liquid medication to flow from the measurement chamber through the needle.