RU2139741C1 - Mixing device, liquid injection device, mixing and delivering device - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: devices are intended for controlled mixing of two or more components in sterile closed medium and obtaining flowing substance with subsequent delivery of the latter from device with accurately adjustable dosing. Device has doing part with power accumulation member of its own in form of elastomeric membrane and mechanism for coupling of medicinal agent vessel with dosing part for controllable mixing of medicinal agent located in phial with diluent positioned in dosing part of device through sterile channel. EFFECT: enhanced treatment efficiency. 37 cl 75 dwg

Description

 This application is a partial continuation of the application N 07/870553, filed April 17, 1993, and in turn is a partial continuation of the application N 07/513917, filed April 24, 1990 and on the basis of which is currently issued US patent N 5122116.

FIELD OF THE INVENTION
The present invention relates generally to fluid mixing and delivery systems. More specifically, the invention relates to a device for mixing certain medications with the aim of obtaining a fluid substance and then infusing the substance to the patient with a precisely controlled speed.

Analysis of the invention
Drug delivery systems that allow separate storage and then control of mixing a specific drug with a diluent for infusion to a patient with precisely controlled speed are finding wider application. In the systems used up to now, the diluent was usually packaged in flexible plastic containers with openings for connecting to devices used to infuse the contents of the container to the patient.

 Typically, for several reasons, drugs are packaged separately from the diluent. One important reason is that some drugs do not retain their effectiveness when mixed with a diluent, and therefore the mixture cannot be stored for a significant period of time. Another reason is that many drug manufacturers do not release medicinal fluids in intravenous containers. Typically, drugs are packaged in powder form in small, sealed containers or vials for subsequent mixing with a suitable diluent. In many cases, it is necessary to mix the drug with diluent immediately prior to infusion to the patient to ensure that the drug does not separate from the diluent before or during infusion. him.

 The infusion of drugs is most often performed in a hospital setting, and a nurse, doctor or other medical staff mix the drug and diluent immediately before the drug is infused into the patient. This mixing operation can be time-consuming and harmful if, for example, toxic drugs are used. In addition, many of the mixing devices used so far are coarse and inaccurate, making accurate, sterile and thorough mixing of the drug and diluent difficult, time consuming and not entirely suitable for home use.

 Currently, several types of closed drug delivery systems are used. Typically, these systems include a flexible container, such as a plastic bag, to which a drug vial can be connected. A flexible container typically contains liquid diluent, and it often includes a brittle element that allows liquid to flow only when it is destroyed. When the drug vial is connected to the flexible container, the vial of the vial is flashed and the fragile element is broken to obtain a sterile communication between the drug vial and the liquid diluent contained in the flexible container. Mixing the drug with a diluent is performed by manipulating a flexible container. Examples of systems of this nature used so far can be described in US Pat. No. 4,584,971 to Boquet et al. And US Pat. No. 4,606,734 to Larkin.

 Another closed delivery and mixing system is described in US Pat. No. 4,458,733 to Lions. The Lyons device includes a compressible chamber with a liquid component placed in it, and the compressible chamber includes a gas absorption compartment and a reservoir communicating with each other. The gas absorption compartment may be connected to a drug-like container containing a miscible component. After the channel is opened, providing communication between the bubble and the gas absorption compartment, mixing is carried out by manipulating the compressible chamber.

 Another very successful solution, a dual capacity system, is described in US Pat. Nos. 4,614,267 to Larkin and 4,641,515 to Tripp and Larkin. In this system, a flexible container with a diluent has a tubular channel that allows you to fix in it a clogged bottle with a drug, as well as a tool to remove the cork. The plug removal tool includes an engagement element, or extractor, which is mounted on a removable cover and hermetically closes the inner end of the channel. In practice, when the bubble is pushed into the tubular channel, the bubble plug is engaged with the extractor, which grabs the plug and pulls it out of the bubble, while the lid is removed from the channel. After removing the cork from the vial, the contents of the vial can be poured into the diluent in the bag and moved with it by manipulating the bag.

 Existing devices of the type described in the previous paragraphs usually use the traditional method of flow flowing under the influence of gravity to infuse the treatment mixture to the patient. This method is cumbersome, inaccurate and usually requires the patient to be in bed. In addition, the flexible bag should be fairly high, and a nurse or doctor should periodically check the device for problems with the infusion device.

 The device that is the subject of the present invention avoids the disadvantages of previous technical solutions due to the complete rejection of the flexible bag, the cumbersome process of mixing drugs using a flexible bag and an inconvenient infusion method under the influence of gravity, which is usually used when using a flexible bag. As will be described in the following paragraphs, the apparatus of the present invention uses newly developed gas-permeable elastomeric films and similar materials, which together with the plate-type base form a liquid chamber in which the first component, such as a diluent, is initially located. Next to the base and communicating with the liquid chamber is a sterile connecting means for effectively connecting a container, such as a drug vial, in which the second component is located. In order to provide controlled sterile mixing of the first and second components, the device includes flow control means designed to control the flow of fluid through the internal channels connecting the fluid chamber and the vial to the drug.

 The device that is the subject of the present invention is small, compact, easy to use and inexpensive to manufacture. The device forms a sterile closed delivery system that can be easily used by patients who are on outpatient treatment or who are being treated at home. Connecting elements are provided on the device’s body, allowing it to be conveniently fixed on the patient’s clothing or attached to the patient’s body with straps.

 The device of the present invention can be used with minimal professional help under changing treatment conditions, for example at home. As an example, it can be pointed out that the devices of the present invention can be used for mixing numerous drugs with suitable diluents and for continuous infusion of mixtures of therapeutic agents, such as antibiotics, analgesics, hormonal drugs, anticoagulants, thrombus solvents, immunosuppressants and the like medicines. Similarly, a device for intraventricular chemotherapy can gently infuse fluid to the patient with accurate dose compliance and when performing micro-infusions over a long period of time.

SUMMARY OF THE INVENTION
The aim of the present invention is to provide a compact, lightweight, low-profile device for the controlled mixing of two or more components in a closed environment in order to obtain a fluid substance and for subsequent delivery of a fluid substance with a precisely controlled speed. More specifically, the purpose of the invention is to propose for use in medicine such a device that can be used both at home and in a hospital setting for accurate mixing and infusion of diluents and selected drugs to a patient who is in outpatient treatment with controlled dosage over long periods of time.

 Another objective of the present invention is to provide a device of the type described above, comprising a dispensing part with its own energy storage means and connection means for quickly connecting the vial with the drug to the infusion system and controlled mixing of the drug in the ampoule with the diluent in the dispensing section through a sterile channel.

 Another objective of the invention is to propose a device of the described class, allowing extremely accurate mixing and delivery of fluid, highly reliable and convenient for use by bed patients in non-hospital conditions.

 Another object of the invention is to propose a device comprising an internal liquid storage tank that can be pre-filled with diluent at the factory or that can be easily filled under operating conditions immediately before use.

 Another objective of the invention is to propose a device of the type described in the previous paragraph, in which the tank is supplied with an elastomeric energy source that can be sterilized by gamma radiation and allows the use of a wider range of sterilization temperatures without compromising integrity and performance degradation.

 Another object of the invention is to provide a device in which mixed liquids can be delivered to a patient either at a constant speed or at a precisely measured variable speed and which can be used in any position and at any height.

 Another objective of the invention is to propose a device that includes means for reliable connection of the vial with the drug with the dispensing part of the device.

 And another objective of the invention is the proposal of the device described in the previous paragraph, which is equipped with means for attaching the device to the clothes or body of the patient.

 An additional objective of the invention is the proposal of a low-profile device for the delivery of fluid of a layered structure, the mass economical production of which can be organized using automated equipment.

 Another object of the invention is to provide a device of the type described, in which liquid is dispensed from the device through a connected infusion device under the influence of a thin, stretchable membrane connected to a thin base of a plate type.

 Another objective of the invention is to propose a device of the type described, in which the stretchable membrane can be represented by a single elastomeric film, a multilayer product or a product of composite materials, gas-permeable in at least one direction, so that gases in mixed liquids can be removed from the liquid chamber and not be introduced to the patient.

 And another objective of the invention is to propose a device of the described class, in which a thin flat filter element is located to the liquid chamber, designed to filter the fluid sent from the reservoir to the patient.

Brief Description of the Drawings
In FIG. 1 is a perspective view of one embodiment of a drug delivery system of the present invention.

 In FIG. 2 is a perspective view of the device shown in FIG. 1 with separation of parts.

 In FIG. 3 shows a top view of the device of FIG. 1 with a partial image of an internal device.

 In FIG. 4 shows a sectional view taken along line 4-4 of FIG. 3.

 In FIG. 5 shows a sectional view taken along line 5-5 of FIG. 3.

 In FIG. 6 shows an enlarged sectional view of the lower right side of the device shown in FIG. 3 illustrating a device of a shut-off and metering valve of a device.

 In FIG. 7 shows an enlarged sectional view taken along line 7-7 of FIG. 3.

 In FIG. 8 is a partial cross-sectional view illustrating a first step in connecting a vial with a drug to the device of the present invention.

 In FIG. 9 is an enlarged perspective view illustrating the shutoff valve of the device in the closed position.

 In FIG. 10 is a sectional view similar to FIG. 8 illustrating a second step in connecting a drug vial to a device of the present invention.

 In FIG. 11 is a sectional view similar to FIG. 10, illustrating the next step in connecting the vial with the drug to the device of the present invention, which shows the mixing of liquids contained in the dispensing part of the device with the drug contained in the vial connected to the dispensing part of the device.

 In FIG. 12 is a sectional view similar to FIG. 11, however, illustrating the next step of transferring the mixed liquid in the drug vial to the dispenser reservoir of the device of the present invention.

 In FIG. 13 shows a sectional view taken along line 13-13 of FIG. 12.

 In FIG. 14 is an enlarged partial view, partially in section, illustrating the construction of the valve mechanism of the drug vial.

 In FIG. 15 is a cross-sectional perspective view similar to FIG. 10, but depicting an alternative embodiment of a drug vial used with the device of the present invention.

 In FIG. 16 is a cross-sectional perspective view similar to FIG. 11 and illustrating the mixing of liquids contained in the dispensing portion of the device with the drug contained in the second embodiment of the drug vial shown in FIG. fifteen.

 In FIG. 17 is a perspective view of another alternative form of apparatus of the present invention.

 In FIG. 18 shows a local top view of the device of FIG. 17, with a partial depiction of the internal structure of the infusion system before it is connected to another form of the container or drug vial.

 In FIG. 19 is an enlarged sectional view showing the initial step of pairing the container with the drug shown in FIG. 18, with the dispensing part of the device.

 In FIG. 20 is a cross-sectional view similar to FIG. 12, depicting the mixing of a diluent contained in a dispensing portion of a device with a drug contained in a final embodiment of a drug vial.

 In FIG. 21 is a cross-sectional view similar to FIG. 12 depicting a transfer operation in which mixed liquids are transferred from a drug vial to a reservoir of a dispensing portion of a device.

 In FIG. 22 shows a local sectional view taken along line 22-22 of FIG. 21, showing means for connecting a vial with a drug to a dispenser of a device.

 In FIG. 23 is a perspective view from behind of another embodiment of the invention.

 In FIG. 24 shows a general perspective front view of a device according to the embodiment shown in FIG. 23.

 In FIG. 25 shows a general perspective view, divided into parts of a device corresponding to this last embodiment of the invention.

 In FIG. 26 shows an image of the device from below.

 In FIG. 27 is a cross-sectional view taken along line 27-27 of FIG. 26.

 In FIG. 28 is a cross-sectional view taken along line 28-28 of FIG. 26.

 In FIG. 29 is a sectional view illustrating the initial step of connecting the container with the drug to the dispenser of the device.

 In FIG. 30 is a cross-sectional view similar to FIG. 11, illustrating the mixing of a diluent contained in a dispenser of a device with a drug contained in a drug vial.

 In FIG. 31 is a cross-sectional view showing a transfer operation in which mixed liquids are transferred to a reservoir of a dispensing portion of a device.

 In FIG. 32 is a cross-sectional view taken along line 32-32 of FIG. thirty.

 In FIG. 33 is a cross-sectional view taken along line 33-33 of FIG. 32.

 In FIG. 34 is a plan view, in partial view, of an internal device of this additional form of a closed drug delivery device of the present invention.

 In FIG. 35 is a fragmentary sectional view taken along lines 35-35 of FIG. 34.

 In FIG. 36 is a side view, partly in section, of a drug vial of this last embodiment of the invention.

 In FIG. 37 is a sectional view illustrating a drug vial connected to a dispensing portion of a device for performing an initial mixing operation.

 In FIG. 38 is a cross-sectional view showing the movement of liquids mixed in a drug vial into a dispenser reservoir of a device.

 In FIG. 39 is a plan view, in partial view, of an internal device of yet another embodiment of a drug delivery system in the present invention.

 In FIG. 40 is a cross-sectional view taken along line 40-40 of FIG. 39.

 In FIG. 41 is a cross-sectional view of a drug container in this embodiment of the invention.

 In FIG. 42 is an enlarged sectional view taken along line 42-42 of FIG. 43.

 In FIG. 43 is an enlarged cross-sectional view showing a drug vial assembly in preparation for conjugation with connecting agents.

 In FIG. 44 is an enlarged sectional view illustrating the initial pairing of the drug with the dispenser of the device.

 In FIG. 45 is an enlarged sectional view similar to FIG. 46 and illustrating the mixing of a diluent with a drug by rotating the vial with the drug relative to a connecting means allowing fluid to flow out of the device’s fluid reservoir towards the chamber.

 In FIG. 46 is a cross-sectional view taken along line 46-46 of FIG. 44.

 In FIG. 47 is a cross-sectional view taken along line 47-47 of FIG. 45.

 In FIG. 48 shows an enlarged sectional view similar to FIG. 45, which shows the further rotation of the drug vial in such a way as to reduce the fluid flow in the direction of the mixing chamber of the drug vial.

 In FIG. 49 is a cross-sectional view taken along lines 49-49 of FIG. 48.

 In FIG. 50 shows a topical, generally perspective view of a fine control valve means for a drug vial in this additional embodiment of the invention.

 In FIG. 51 is an enlarged, generally perspective view of a medication bottle divided into parts, illustrating the construction of an accurate flow control device in the present invention.

 In FIG. 52 is a plan view of another form of a drug vial assembly in the present invention.

 In FIG. 53 shows an enlarged sectional view of the bubble of FIG. 54.

 In FIG. 54 is an enlarged sectional view showing a new drug vial in a ready position to interface with the device’s connecting means.

 In FIG. 55 is an enlarged sectional view showing the initial conjugation of a vial with a drug with the dispensing portion of the device.

 In FIG. 56 is an enlarged sectional view showing the initial mixing of a diluent with a medicament contained in an alternative embodiment of a drug vial.

 In FIG. 57 is a fragmentary sectional view taken along line 57-57 of FIG. 56.

 In FIG. 58 is an enlarged sectional view similar to FIG. 56 illustrating a decrease in fluid flow in the direction of the mixing chamber of a drug vial.

 In FIG. 59 is a fragmentary sectional view taken along line 59-59 of FIG. 58.

 In FIG. 60 is a fragmentary sectional view taken along line 60-60 of FIG. 58.

 In FIG. 61 is a perspective perspective view of valve devices for fine adjustment of a container assembly of the latter form of the invention.

 In FIG. 62 is a partial cross-sectional view of a portion of a mixing chamber of a device showing a tablet drug.

 In FIG. 63 is a top view of yet another drug vial assembly of the present invention.

 In FIG. 64 is a fragmentary sectional view taken along line 64-64 of FIG. 63.

 In FIG. 65 is a perspective perspective view, with a breakdown into parts, of a container assembly of this latter embodiment of the invention.

 In FIG. 66 is a perspective perspective view of various forms of additive means or nodes with a substrate for this last form of the invention.

 In FIG. 66A, 66B, 66C, and 66D are general schematic illustrations illustrating various affinity attachment of ligands, protein molecules, and enzymes to a substrate.

 In FIG. 67 is an enlarged, generally perspective image, divided into details of another embodiment of the present invention.

 In FIG. 68 is an enlarged sectional view of the embodiment shown in FIG. 67, assembled, ready to use, but with an empty fluid reservoir.

 In FIG. 69 is an enlarged sectional view similar to FIG. 68, on which the fluid reservoir is full.

 In FIG. 70 shows an enlarged, generally perspective view of one of the cannulas of a blunt-ended device.

 In FIG. 71 is an enlarged, generally perspective image with detailing of yet another embodiment of the present invention.

 In FIG. 72 is an end view of a container of a diluent device.

 In FIG. 73 is a cross-sectional view taken along line 73-73 of FIG. 72.

 In FIG. 74 is an enlarged cross-sectional view of the drug vial of the device before it is placed in the connection assembly of the device.

 In FIG. 75 is an enlarged sectional view of the embodiment shown in FIG. 71 the way it looks when assembled.

Description of the invention
In the drawings, and in particular in FIG. 1 and 2, a device is shown showing one embodiment of the present invention, generally indicated at 12 and used to mix a first component contained in a separate container, such as a drug vial, indicated at 14, with a second component contained in a reservoir inside the dispensing part of the device in order to obtain a fluid suitable for infusion and for subsequent infusion of fluid to the patient at a controlled speed. In this embodiment of the invention shown in FIG. 1-11, the device consists of a housing 16 including a first, cylindrical part 18, and a second part, an infusion system 20.

 As can be seen in FIG. 2, the first part 18 includes connecting means for quickly connecting the container 14 to the infusion system of the device 20. The second part 20 of the housing 16, the construction of which will be described in more detail below, consists of an integral part of the infusion system device and includes a base unit 21, consisting of generally a flat plate base 22. The base 22 includes an inlet 24 and a liquid outlet 26, which communicate with each other through a multi-channel fluid channel 28. The liquid channel 28 includes a first transverse a thread 28a that communicates with the inlet 24, a second lateral thread 28b, and two longitudinal threads, or channels, 28c, that connect the threads 28a and 28b. The transverse thread 28b is in fluid communication with the fluid inlet 26 as shown in FIG. 2.

 As can be seen in FIG. 4 and 5, a device of this type of implementation of the invention also includes a stretchable membrane 30 made of an elastic material. The membrane 30 is adjacent to the base 22 and together with it forms one or more tanks or chambers 32 for diluent. The membrane 30 is stretched by a liquid, which is introduced under pressure into the chamber 32 through the closing inlet channel 33 at the base 22. The elasticity of the membrane 30 is such that, when stretched, it tends to return to its former less stretched state. This causes the fluid to flow out of the device when the controls are open through the outlet 26. The design features of both the flow controls and the membrane 30 will be discussed in the following paragraphs.

 Between the stretchable membrane 30 and the upper flat surface 22a of the base 22 are means for creating an empty space in the chamber 32. These means are in the form of two separate protrusions 34. A longitudinal first groove or channel 36 is provided in each of the protrusions 34. When the device is assembled as shown in FIG. 4 and 5, the slots 36 are superimposed exactly on the parallel channels for the liquid 28c and the membrane connection means shown here in the form of protrusions 34 are pushed up into the liquid chambers 32, forming an empty space in them. During operation of the device, when the stretchable membrane 30 tries to return to a less stretched state, it comes into contact with the upper surfaces of the protrusions 34 and, when this happens, forces the fluid contained in the chambers 32 into the channels 28c through the grooves 36 (FIG. 5). The configuration of the protrusions 34 is such that when the membrane returns to its original flat shape, a controlled release of almost all the fluid from the chambers 32 is ensured.

 A porous plastic, gas permeable, structural filling element 40 is superimposed on top of the stretchable membrane 30. As best seen in FIG. 5, two longitudinal channels 42 with a concave surface are provided in the element 40, to the inner walls 43 of which the membrane is initially pressed, being stretched by the liquid supplied under pressure from the inlet 33 made in the base unit 21 to the chambers 32.

 The base 22 and the element 44 are covered and hermetically insulated by a solid plastic casing 44. The casing 44 includes a first part 44a forming an upper segment of the cylindrical part 18 of the casing 16 (Fig. 2). As will be described below, in the cylindrical part 18 are located the connecting means of the device, including the first means of regulating the flow and designed to quickly connect the vial with the drug with the infusion system of the device. The casing 44 also has gas passing means represented by several openings 46 formed in the upper wall of the casing 44. When the stretchable membrane 30 is made of a gas permeable material, gas passing means, including openings 46, allow any gases contained in the fluids entering the chambers 32, pass through a gas-permeable membrane, through aggregate 40 and enter the atmosphere through gas passage means. The gas passage openings 46 are covered by a label 48 indicating drug, which may also be gas permeable. Another part of the housing 44 is a removable tape clip 50, provided with a groove 52 in the form of a swallow tail, which mates with a protruding connecting spike 54 made on the upper surface of the housing 44.

 The base unit 21 also includes an outlet 56, usually closed by a removable cover 58. The outlet 56 communicates with the outlet for liquid 26 through the pipe 57. The outlet 56 also communicates with a transverse channel 60, ending at its outer end with an opening 62 (Fig. 2 ) The outlet flow control means is introduced into the opening 62, shown here as a shut-off and metering liquid means 63, consisting of a needle valve of a standard design with an elongated valve stem or element 64, which fits tightly into the channel 60 (Figs. 2 and 6). A regulating handwheel 66 is provided at one end of the stem 64. A cone portion 68 is provided at the other end, adapted to fit with the valve seat 69 located on the base 22, or to cut off almost completely, or to control the restriction of fluid flow from the device through the pipe 57 and an outlet 56. As is more clearly seen in FIG. 6, there is an internal thread in the channel 60, which includes a thread 70 on the outer surface of the stem 64. With this design, rotation of the handwheel 66 allows the valve element to be moved along the channel 60 in the axial direction to effect a controlled displacement of the valve cone 68 relative to the channel 57 and contact with the valve seat 69 so as to control fluid flow through the channel 57. The gasket ring 67 provides a seal to the stem 64 relative to the channel 60.

 Turning now to FIG. 8, which shows the construction of a container, or system with a vial of the drug 14 of the device of the present invention. In this form of the invention, the container includes second flow control means for controlling the flow of fluid entering and leaving the inner chamber 75 of the bubble 76. A plastic lid, or package 78, is fitted tightly on the bubble 76, or package 78 provided with means for fixing the bubble, presented here in the form of two spacers located at a certain distance from each other, protruding around the circumference of the latches 80 and 82, the purpose of which will be described below. Each of the protruding circumferentially latches 80 and 82 has a protruding outer flat surface 83, which should engage with one of two annular stops 18a and 18b located at a certain distance from each other, made on the inner surface of the cylindrical part 18 (see also FIG. . 2). The annular stops 18a and 18b are a new locking means adapted to engage with the bubble fixation means provided on the drug bubble block to prevent the drug bubble from escaping from the cylindrical portion 18 after it is inserted into and aligned with it.

 The second flow control means in this first embodiment of the invention is a plunger that fits fairly tightly into the bubble 76. The bubble 76 can move relative to the plunger 86 between the first position shown in FIG. 8 and 10, and the second position shown in FIG. 11, and between the second position and the third position shown in FIG. 12. The plunger 86 is generally cylindrical in shape and provided with a skirt 86a that is substantially sealed against the inner wall of the bubble 76. The plunger also includes a first locking means, or engagement means, shown here as thread 86b, for interlocking with the connecting means of the device. In the inner channel 86c formed in the plunger, plunger valve means are arranged in the form of valve assembly 88. As can be seen in FIG. 14, the valve assembly 88 includes a central part of a cylindrical shape 90 closed on one side by a disc-shaped part 92. In the cylindrical wall of the central part 90 next to the part 92, which is preferably integrally formed with the part 90, fluid openings 94 are provided. On the opposite the end of the Central part 90 is made of an annular element 96.

 As best seen in FIG. 8 and 10, the plunger 86 has a central portion 87 including spaced apart, protruding inward seats or shoulders 100 and 102. When the valve assembly 88 is in the closed position shown in FIG. 8, the periphery of the part 92 is essentially sealed against the shoulder 100, and the annular element 96 is at a certain distance from the shoulder 102. On the other hand, when the valve is in the open position shown in FIG. 10, the periphery of the part 92 is at a certain distance from the shoulder 100, and the annular element 96 of the valve element is pressed against the shoulder 102. If desired, the Central part 90 can be made so as to support the rod 106 during axial movement of the rod 106 in the Central part of the housing. When the valve is in the open position shown in FIG. 10, fluid may flow from the central channel 103 of the valve through the radically directed openings 94 into the bubble as shown by the arrows in FIG. ten.

 The valve assembly 88 is moved from a closed to an open position by means of controls including, in this case, the stem of the plunger 106, which is integral with the disk-like part 92 and, as shown in FIG. 8 and 14, passes axially along the channel of the valve 103. As will be described below, the control means control the first and second regulatory means that are the subject of the present invention, including the valve assembly 88, and are designed to control the flow of fluid into the drug vial 14 and arising from it.

 Before considering the operating procedure of the control means, we will consider the previously described connecting means for connecting the tank 14 to the housing part 18. As best seen in FIG. 2, 3 and 8, the connecting means here consist of a sterile connecting block 110, which is held in the center of the cylindrical part of the housing 18 by a rigid connecting element 111 located in the transverse direction relative to the part of the housing 18. The connecting block 110 consists of an outer cylindrical part 112 provided with a second connecting means or internal thread 113 and coaxially located inner cylindrical part 114. The inner part 114 is rigidly held inside the outer part 112 by an annular second end wall 116 (FIG. 8). As best seen in FIG. 2, the end wall 116 fits snugly into a recess or groove 118 formed in the connecting element 111. A part of the connecting element 111 is also a radially protruding element of the connector 120 with the internal fluid channel 122, which communicates with the inlet 24 in the base 22 when the support 111 is mounted inside the cylindrical portion 18 as shown in FIG. 3 and 8. The channel 122 is in communication with the channel 124 formed by the inner walls of the cylindrical part 114. A smaller diameter channel 126 is connected to the channel 124 in the valve seat forming the conical part of the wall 128 (Fig. 8).

 In FIG. 9 shows a connecting valve means, generally indicated at 136, which is also part of the connecting means of the present invention, and which performs reciprocating movement in the channel 124, being intended to control the fluid flow in the channel 126 in a manner that will be described below . As shown in FIG. 8 and 9, the connecting valve means 136 includes a valve element 137 consisting of a body 138 and a connecting rod 140. At the junction of the parts 138 and 140, the wall 142 is tapered and can fit almost tightly into the valve seat formed by the conical wall 128 when the valve is in the closed position shown in FIG. 8. When the device of the invention is in storage mode, the open end of the connection block 110 is closed by a removable sealed cover 130 provided with a hinge 132 for use when removing the cover from the sterile connection (Fig. 2).

 In the process of using the device of the invention, first, the lid of the vial 146 is removed from the drug vial 14 (FIG. 2). After that, the lid 130 covering the channel of the sterile connecting block 110 is removed, and the open end of the drug vial 14 is inserted into the open end 148 of the cylindrical part 18 (Fig. 8). After the drug vial 14 is inserted into the open end 148, the retainer 80 on the outer shell passes through the stop 18a on the cylindrical part 18 and the thread 86 enters into the thread 113 made on the connecting element 113. Clockwise rotation of the vial with the drug causes contact a plunger with a connecting element as shown in FIG. 10. After the parts have joined together, the valve stem valve 106 will come into contact with the valve stem 140 of the valve means 136, causing the first flow control means and the valve element 92 of the second flow control means 92 to open in the axial direction, shown in FIG. 10. With the flow control valves in this position, the expandable membrane 30 will cause the fluid contained in the chambers 32 to flow under pressure through the valve seat 128 into the fluid channel 126 of the connecting means and then into the channel 103 of the tank valve means. The pressurized fluid then flows into the radial openings 94 of the container valve and immediately afterwards into the interior of the container 76 as shown by the arrows in FIG. 10. Such a rapid flow of liquid under pressure into the drug vial will cause a mixing or dilution process.

 As shown in FIG. 11, the fluid entering the drug vial will be mixed with the drug M contained in the vial, so as to obtain a fluid substance consisting of a mixture of the liquid stored in the chambers 32 and the drug M stored in the vial. It is important to note that when fluid under pressure rapidly enters the drug vial, the vial will move in the outward direction shown in FIG. 11, the surface 83 of the locking means or retainer of the bubble 80, made on a plastic shell, will come into contact with the first stop element 18a, made on the inner surface of the cylindrical part of the housing 18. It should be noted that in this position the plunger 86 will move from an intermediate position inside the bubble 76, as shown in FIG. 8 to the outward position shown in FIG. 11, in which the plunger 76 is located next to the open neck of the glass container 76. The air in the bubble 76, if any, promotes a turbulent mixing process.

 The diluted mixture, drug M, stored in the container 14, and residual air, if any, are transferred back to the infusion system reservoir by applying an inward directed force to the drug vial in the direction indicated by arrow 150 in FIG. 12. After the drug vial 14 is reinserted into the cylindrical portion 18, the diluted mixture located in the drug vial is passed through the radial openings 94 of the drug valve into the valve channel 103, then into the channel 126, passes through the valve seat 128 and then into the channel 124 of the connecting means. After that, the fluid will enter through the channels 122 and 28 into the chambers 32 (Fig. 5). The air trapped in the liquid, if any, will be released into the atmosphere through the gas permeable elastomeric membrane 30 using a gas transfer process. As shown in FIG. 13, a plurality of circumferentially arranged fluid channels 152 are provided on the inner wall of the inner cylindrical element 114 of the connecting means, designed to facilitate the flow of liquid from the chambers 32 made in the drug infusion system of the device into these chambers.

 In FIG. 12 it can be seen that the persisting inward pressure applied to the drug vial 14 will cause the retainer 80, made on the shell 78, to pass through the second stop 18b, made on the inner surface of the cylindrical chamber 18, and be fixed in it. Similarly, the latch 82 passes through the first stop 16a of the cylindrical part 18 and locks in the stopper 18a. In the configuration of parts of the device shown in FIG. 12, the drug vial 14 is tightly fixed in its position in the cylindrical chamber 18 of the housing 16.

 The intake of the diluted mixture of the first and second components contained in the vial 14 into the chamber 32 caused by the telescopic movement of the drug vial into the cylindrical portion 18 will cause the partially stretched membrane 30 to move to the stretched position shown in FIG. 5. After stretching, the membrane 30 will constantly develop pressure on the completely mixed liquid contained in the chambers 32, so that after removing the cover 58 and opening the needle valve 64, the freshly diluted drug and diluent forming the combined mixed components of the liquid will be infused into the patient in controlled doses through any suitable connecting means, such as an infusion needle, attached to the channel shown in FIG. 1 by a dotted line and indicated by 154. As shown above, the dosage of fluid infusion to a patient from the device of the present invention can be precisely controlled by manipulating the needle valve 64.

 The high performance of the device is facilitated by the use of several modern types of materials in its manufacture. These materials significantly contribute to improving the reliability, accuracy and ease of manufacture of the device. Before considering alternative embodiments of the invention shown in the drawings, a brief description of the materials used in the manufacture of the device that is the subject of the present invention is given.

 As for the base 22 and cover 44, it is possible to use a wide variety of materials, including metals, rubber or plastics, compatible with the fluids with which they come in contact. Examples of such materials include stainless steel, aluminum, latex rubber, butyl rubber, nitrile rubber, polyisoprene, styrene butadiene copolymer, silicones, polyolefins such as polypropylene and polyethylene, polyesters, polyurethane, polyamides and polycarbonates.

 As for the further elastic stretchable membrane 30, this important component can be made of several alternative materials, including rubber, plastics or other thermoplastic elastomers. These include latex rubber, polyisoprene (natural rubber), butyl rubber, nitrile rubber, polyurethanes, ethylene-butadiene-styrene copolymers, silicone-modified polyurethanes, fluorocarbon elastomers, fluorosilicon, fluoroalkoxyphosphazienes, multimeric copolymers and other polymer systems , grafted, crystalline and star-shaped block copolymers), mechanical polysmixes and interpenetrating polymer networks.

Examples of materials that have proven particularly suitable for this application are: silicone polymers (polysiloxanes) and high-quality silicone elastomers made from polymers with a high molecular weight with the addition of suitable fillers. These materials can be cast into thin-film membranes and have high permeability (allowing maximum transfer of vapor and gas through the membrane), high adhesion and tensile strength, as well as excellent low-temperature ductility and radiation resistance. In addition, silicone elastomers retain their properties in a wide temperature range (from -80 ^o to 200 ^o C), stable at high temperatures and demonstrate tensile strength up to 2000 psi with an elongation of up to 600%.

In addition, silicones (polyorganosiloxanes) are thermally stable, hydrophobic organometallic polymers with the lowest p-p interaction among all polymers supplied by the industry. This fact, along with the flexibility of the main chain contributes to a low glass transition temperature (-80 ^o C) and to obtain an amorphous structure for high molecular weight polymers (polydimethylsiloxanes). Silicone rubber membranes are significantly more permeable to gases than membranes of any other polymer. Depending on the applied medicinal fluid and filling in the storage mode, which determine the desired characteristics of the mass transfer of the membrane (permeability and selectivity), other materials that can be selected include polyurethane polysiloxane copolymers, mixtures, and interpenetrating polymer networks. For example, a multicomponent interpenetrating polymer network of polydimethylsiloxane and polyurethane, comprising 10-20% by weight of polyurethane, shows an improved initial modulus compared to polydimethylsiloxane itself.

, чтобы получить биосовместимые сопряжения, не оказывая заметного влияния на проницаемость мембраны.The interpenetrating polymer network is a unique mixture of cross-linked polymers that are essentially free of covalent bonds or graphites. True
interpenetrating polymer networks are also homogeneous mixtures of their constituent polymers. Other examples of additional candidate materials could be polyurethane polysiloxylane interlayered with polyparaxylene or alternately polydimethylsiloxane and polyparaxylene. Co-extruded layered materials of this type can be selected in accordance with the required gas permeability for diffusion of steam, O ₂ , N ₂ and CO ₂ , as well as certain requirements for their selectivity and the direction of gas migration with proper layering. In addition, mating surface layers of various materials with a thickness of the order of 5 to 20 can be made on the membrane

to obtain biocompatible conjugations without having a noticeable effect on membrane permeability.

 As for structural aggregate 40, many types of porous plastic materials can be used for it. In some embodiments of the invention, this component can be made from one of several polymer groups. The plastic structure of this component typically includes a complex network of open multidirectional pores. Pores can range in size from 0.8 microns to 2000 microns and provide plastic with a unique combination of gas permeability and mechanical strength. In addition, the material is durable, lightweight, highly resistant to chemical influences and, depending on the specific configuration of the device, can be flexible. In terms of hardness, it can be soft, elastic or rigid, and depending on the specific microdiameter required it is possible to use the following polymers: polypropylene, ultra-high molecular weight polyethylene, high-density polyethylene, polyvinyl diene fluoride, ethylene vinyl acetate, styrene acrylonitrile, polytetrafluoroethylene.

 An alternative material for the manufacture of the housing 40 and the base 22, which could serve as a gas-tight barrier, is a material that offers the company "B-P Cheminals International", Cleveland, pc. Ohio, under the Barex trademark. This material, pure rubber, modified with an acrylonitrile copolymer, which is widely used in the packaging industry due to its excellent gas impermeability, resistance to chemical influences and suitability for extrusion (thermoforming) and injection molding. A product using this and similar impermeable materials can be made either in a single layer or by coextrusion (with other materials such as polyethylene, polypropylene, polystyrene and other modified styrenes). A combination of different materials can be used to improve the desired physical properties of the thermoformed part.

 Turning now to FIG. 15 and 16, showing a second embodiment of the present invention. In this form of the invention, the first and second parts of the housing and part of the device with the infusion system are identical in design and principles of operation with the first embodiment, and identical parts are denoted by the same positions. However, the container assembly generally indicated in FIG. 15 and 16, position 200, is slightly different.

 The container assembly 200 consists of a glass vial 202 with a chamber 204 designed to contain the medicine M. The plastic case or shell 206 is tightly mounted on the vial 202 and includes the first and second latches 208 and 210, which are identical to the latches 80 and 82 described above. Inside the bubble 202, second flow control means is arranged in this embodiment of the invention, for controlling the flow of fluid entering and leaving the chamber 204. In this case, the second flow control means consists of a plunger 212 that fits tightly into the bubble 202. The device of the plunger 212 is generally similar to the device of the plunger 86: it has a cylindrical shape and a skirt 214 that is in close contact with the inner wall of the bubble 202. Plunger 212 also includes similar connecting means shown here in the form of a thread 216 for engagement with a thread 113 formed on the connector 112.

 However, in this second embodiment, the plunger 212 provides an internal channel 218, which is usually closed by a brittle or pierceable diaphragm 220 located across it. The first valve means, presented in this case as valve assembly 222, is located in the channel 218 and together with the diaphragm 220 regulates the fluid flow through the channel 218. The plunger 212 includes an inwardly facing flange 224, into which the flange 226, generally made on the valve assembly 22, abuts (Fig. 15). The valve assembly 222 also includes a stem 228, which in this embodiment is part of a control device for controlling a connector valve and a plunger valve. Around the stem 228 is a fluid channel 230. The stem 228 is integral with the plunger body and terminates at 232. As shown in FIG. 15 when the valve assembly 222 is in the normal position shown in FIG. 15, point 232 is in contact with aperture 220.

 When using a device representing a second embodiment of the invention, when the plunger 214 is screwed onto the thread of the connecting element 112 as shown in FIG. 16, the valve assembly 222 will be shifted to the right by the valve stem 140 of the connecting member 136, with the diaphragm 220 being pierced. At the same time, valve 136 will shift axially and open, allowing fluid in the reservoir of the device's infusion system. flow through the channels 230 into the chamber 204 of the vial 202 and mix with the drug M. The pressurized fluid flowing from the reservoir of the device infusion system moves the container assembly outwardly to the position shown in FIG. 16, in which the latch 208 engages with a stop 18a formed in the first part 18 of the housing 16. After completion of this dilution process, the diluted liquid flows under pressure into the reservoir of the device’s infusion system in the same way as described above, by displacing the container assembly to the left, as shown in FIG. 16, and in a fixed position similar to that shown in FIG. 12 and as previously described.

 In FIG. 17-22 another embodiment of the invention is illustrated. The infusion system, which is part of the device, in this embodiment of the invention is essentially identical in design and operation of this system in the first two forms of implementation of the invention, and the same reference numbers are used to indicate the same details. However, the connecting part of the device is somewhat different, as is the design of the drug vial assembly, indicated here at 300.

 The infusion system of this third embodiment of the invention also includes a base unit 21 c, generally a flat base 22. The base 22 has a fluid inlet 24 and a fluid outlet 26 (not shown) that communicate through a multi-channel fluid channel 28. As and previously, the fluid channel 28 includes a first transversely spaced thread 28a in communication with the fluid inlet 24, a second transverse spaced thread 28b (not shown) and two longitudinally p memory location thread or channel, 28c, which are interconnected by strands 28a and 28b. The transverse thread 28 communicates with the outlet 26 in the same way as shown in FIG. 2.

 The device in this embodiment also includes a stretchable membrane 30 made of an elastic material. The membrane 30 is adjacent to the base 22 as described above, and together with the base forms one or more reservoirs or chambers 32 for storing the diluent of the type shown in FIG. 5. The membrane 30 can be stretched by a fluid flowing under pressure into the chambers 32 through a lockable inlet 33 made in the base 22 (Fig. 18). As in the previously described embodiments of the invention, the elasticity of the membrane 30 is such that the membrane, when stretched, tends to return to its original configuration with less stretching. This causes fluid to flow out of the device through the fluid outlet after opening the flow control means provided by the present invention.

 Between the stretchable membrane 30 and the upper flat surface 22a of the base 22 are means for creating an empty space in the chamber 32. These means in this case also take the form of two separate protrusions 34. A longitudinal first groove and a channel 36 are provided in each of the protrusions 34. When the device is assembled as shown in FIG. 4 and 5, the slots 36 are superimposed exactly on the parallel channels for the liquid 28c and the membrane connection means shown here in the form of protrusions 34 are pushed up into the liquid chambers 32, forming an empty space in them. During operation of the device, a stretchable membrane 30 forces the fluid contained in the chambers 32 to force out of the device through the outlet 56, as described above. The design and use of flow control or cut-off and metering means 63 have also been described above.

 A porous plastic, gas-permeable, structural filling element 40 (not shown in FIG. 17), which, in turn, is covered with a cover 44 of the type described above, is superimposed on top of the stretchable membrane 30.

 The first housing part, indicated in FIG. 17 at 302 has a slightly different construction from the first part of the housing 18. Instead of the stops 18a and 18b of the type shown in FIG. 2, the first part of the housing 302 in this case is provided with an internal thread 304, the purpose of which will be explained later. Part 302 is also provided with means for fixing the container in the form of elastic ratchet teeth 306 engaged and fixing ratchet mating teeth 308 made on the container for a drug vial.

 The connecting means of this third embodiment of the invention are essentially identical to the connecting means of the previously described embodiments of the invention and consist of a sterile connecting unit 110, which is held in the center of the cylindrical part of the housing 302 by a rigid connecting element 111 located in the transverse direction relative to the part of the housing 302. The connecting block 110 consists of an outer cylindrical part 112 with an internal thread 113 (FIG. 19) and a coaxially disposed inner cylindrical part 11 4. As before, the inner part 114 is rigidly held inside the outer part 112 by means of an annular end wall 116 (Fig. 19). As best seen in FIG. 19, the end wall 116 fits tightly into a recess or groove 118 formed in the connecting member 111. A part of the connecting member 111 is also a radially protruding member of the connector 120 with an internal fluid channel 122 that communicates with the inlet 24 in the base 22 when the support 111 is mounted inside the cylindrical portion 302 as shown in FIG. 17 and 18.

 As shown in FIG. 19, channel 122 is in communication with a channel 124 formed by the inner walls of the cylindrical portion 114. A smaller fluid channel 126 is connected to a channel 124 in the valve seat portion of the conical wall portion 128. The valve means, generally indicated at 136, which is also described previously, performs reciprocating movement in the channel 124, being designed to control the flow of fluid in the channel 126 in a manner that will be described below. As shown in FIG. 8 and 9, the valve means 136 includes a valve element 137 consisting of a body 138 and a stem 140. At the junction of the parts 138 and 140, the wall 142 is beveled to the cone and can practically leak into the valve seat formed by the conical wall 128 when the valve is in the closed position shown in FIG. 19. When the device of the invention is in storage mode, the open end of the connection block 112 is closed by a removable sealed cover 130 of the type shown in FIG. 1.

 In the embodiment of the invention shown in FIG. 17-21, the container assembly 300 includes a second flow control means for controlling the flow of liquid entering and leaving the inner chamber 309 of a glass vial 310 (FIG. 19), which contains the drug M. The second flow control means in this embodiment of the invention is similar in arrangement and principles of operation to those described previously and includes a plunger 86 that fits fairly tightly into the vial 310. The plunger 86 also includes a binder, shown in the form of a thread 86b, to provide ides with the coupling means of the device. As previously, the valve assembly 88 controls the fluid flow passing through the channel 86c formed in the plunger 86, and is controlled by the control means described above. However, as can be seen in FIG. 19 and 20, the plunger 86 is provided with circumferential channels 89 and 91 made around its circumference, which are essentially hermetically sealed by the parts 92 and 96 of the element 90, respectively.

 The glass vial 310 is placed in an assembly cover or shell 312 surrounding the vial and provided with the above-described circumferentially extending ratchet teeth 308. An external thread 314 is made adjacent to the open end of the cover 312 and mates with an internal thread 304 made in the cylindrical part of the device body . The bubble 310 (FIG. 18) is closed by a tear-off cap, such as 311, which is integral with the front 213f of the shell 312.

 In the process of using the device of the invention, the cap 311 is first removed from the drug vial assembly 300. After that, the lid 130 covering the channel of the sterile connecting element 110 is removed and the open end of the drug vial 300 is inserted through the open end 148 of the cylindrical portion 302 (Fig. 19). After the drug vial 300 is inserted into the open end 148, the thread 314 engages with the first internal thread 304a formed in the cylindrical portion 302 (FIG. 19). At the same time, thread 86b will mate with thread 113 provided on connector 112. Rotating the drug clockwise will pair the thread 314 with the first internal thread 304a and pair the threads 86b of the plunger 86 with the thread 113 of the connector 112 as shown in FIG. 20. The teeth 308, made in the shell 312, will also engage with the ratchet teeth 306. After the plunger mates with the element 112, the valve stem valve 106 contacts the valve means valve stem 140, causing axial movement of the valve means 136 as well. element 137 of the first flow control means and the valve element 92 of the second flow control means to the open position shown in FIG. 20. With the flow control valves in this open position, the expandable membrane 30 will cause the fluid contained in the chambers 32 to flow under pressure through the valve seat 128 into the fluid channel 126 of the connecting means and then into the channel 103 of the tank valve means. The pressurized fluid then flows into the radial openings 94 of the container valve and immediately afterwards into the interior 309 of the glass container 310 as shown by the arrows in FIG. 20. Such a flow of liquid under pressure into the drug vial will cause a mixing or dilution process.

 As shown by the arrows in FIG. 20, the fluid entering the drug vial will be thoroughly mixed with the drug M contained in the vial in such a way as to obtain an active drug fluid consisting of a mixture of the liquid stored in the chambers 32 and the drug M stored in the vial.

 After mixing the drug M with the diluent, the drug vial assembly is rotated again clockwise. During this additional rotation, the drug vial thread 314 will move along the circumferential void space 316 provided in the cylindrical portion 302. As shown in FIG. 20, space 316 serves as an intermediate space and is located between the first portion of thread 304a and thread 304. Continuing clockwise rotation of the drug vial will conjugate thread 314 with thread 304, moving the drug vial assembly from the position shown in FIG. 20 to the stop position shown in FIG. 21. The ratchet teeth 308 on the shell will also mesh with the elastic ratchet teeth 306 formed on the inner surface of the housing portion 302. As best seen in FIG. 22, the ratchet teeth 306 are made in such a way that they can elastically deform, allowing free rotation of the drug bubble assembly clockwise, but engage with the teeth 308 as shown in FIG. 22, preventing rotation of the drug bubble assembly counterclockwise. With such a device, after pairing the vial assembly with the drug with the cylindrical portion 302, it cannot be easily removed.

 Moving the drug vial assembly to the position shown in FIG. 21, causes the reconstituted mixture to return to the infusion system through channels 94, 103, 126, 124, 122 and 28 to enter the chamber 30 and then mix with the diluent, followed by infusion to the patient in the manner described previously.

 The label covering the peripheral surface of the shell 312 and connecting the front and rear portions 312f and 312r may be marked with numbers, color codes, or the like to indicate the position of the vial assembly when connecting, diluting, and returning the diluted drug to the cylindrical portion 302 Such designations are useful in teaching bed patients to use the device.

 In FIG. 23-33 show another embodiment of the present invention. This fourth embodiment is completely different in appearance, but likewise includes a drug vial or container assembly similar in design and operation to the container assembly 300 of the third embodiment. Accordingly, with the same reference numerals in FIG. 23-33, identical parts forming a container assembly are indicated. The connecting parts of the connecting means of the present embodiment are also identical to those described previously with reference to FIG. 17-22. However, having a cylindrical shape, the first part of the device housing in which the connecting means are located, indicated here at 400, has a slightly different device, like the second part of the housing in which the device infusion system is located. The device, which is this fourth form of implementation of the invention, is generally larger in size than the devices corresponding to the previously described embodiments of the invention, and is intended for dispensing more significant volumes of drugs.

 Specifically in FIG. 23, 24 and 25, the second part, or the infusion system, generally indicated at 402, consists of a base unit 404, including a curved base element 406 with front and rear surfaces 408 and 410. The middle part 407 of the base element 406 has many small, overlapping world channels 412 for the passage of fluid in communication with the longitudinal central collecting channel 414, consisting of separate sections 413 and 416 (Fig. 29). The purpose of these channels and parts will be described below. The lateral sections 418 of the base element 406 have openings 420 that can be used to hold the device in the process of working with it, or tapes can be passed through the bottom with which you can attach the device to the patient’s body.

 A thin, generally flat, stretchable elastomeric membrane, or element, 430 is thermally bonded and forms, together with the central portion 407 of the base 406, a chamber 422 (FIG. 27). Element 430 is pulled off the plane as shown in FIG. 27. when applying pressure fluid to the chamber. As the stretchable element 430 is stretched by liquid pressure, internal stresses arise in the element, which cause the element to constantly tend to return to its original position with less tension.

 An important feature of this last form of implementation of the device, which is the subject of the present invention, is the use of a filter device located in the chamber 432 and designed to filter the fluid coming from the chamber 432 into the fluid channels 412 made in the base element 406. The filter device can also be used as a boundary trap for bubbles. In the shown embodiment, the filter device is made in the form of a thin, microporous film, a layered or composite membrane 434, which is placed on the front surface 408 of the base 406 as shown in FIG. 27. The front surface 408 supports the filter 434. The membrane 434 can be made of a variety of filter materials whose properties are obvious to those skilled in the art, including cellulose acetate, polytetrafluoroethylene, polypropylene, plvinyl diene fluoride and a polyurethane / polyethylene composite.

 A porous plastic, gas-permeable, structural filling element 436 is superimposed on top of the stretchable membrane 430. As best seen in FIG. 27, in the element 436 there is provided a centrally located longitudinal channel 438 with a concave surface, to the inner wall 440 of which the membrane 430 is initially pressed, being the maximum stretched liquid entering under pressure into the chamber 432. The element 436 can be made of the same material as described above in connection with element 40.

 The element 436 is covered and hermetically sealed with a solid plastic casing 442. The casing 442 also has gas transmission means represented by several openings 444 made in the upper wall of the casing. When the stretchable membrane 430 is made of a gas-permeable material, gas passage means, including openings 444, allow any gases contained in the liquids entering the chamber 432, if any, to pass through the gas-permeable membrane, through filler 436 and into the atmosphere through the passage openings gases. The gas passage holes 444 are covered by a removable portion label 446. In some cases, the lid and base may be made of similar materials of the type described previously.

 The base assembly 404 also includes an outlet 448, typically closed by a removable cover 450. The outlet 448 communicates with a fluid outlet 414 and an outlet 417 through a nozzle 452 (FIG. 28). The channel outlet 448 also communicates with a transverse channel 454 formed in the base 406 and ending at its outer end with a hole 456 (FIG. 28). An outlet flow control means, shown here as a shut-off and liquid metering means of the type described above and indicated in FIG. 2 through 6 by 63. As already described above, the needle valve 63 either closes or substantially restricts the flow of fluid flowing from the device through the channel 414 and the outlet 448. As can be seen in FIG. 28, there is an internal thread in the channel 454, which includes a thread 458 on the outer surface of the stem 460. With this design, rotating the handwheel 462 on the stem 460 allows the valve element to be moved along the channel 454 in the axial direction to effect a controlled displacement of the conical portion 464 of the stem 460 the inner end relative to the channel 454 and in contact with the valve seat 464a, made in the base 406 (Fig. 28). The spacer ring 463 provides a seal to the stem 460 relative to the channel 454. Alternatively, or simultaneously with the needle valve, the channel 452 may be initially hermetically sealed by an internal septum 465 (FIG. 23), which may be punctured with the tip provided on the intravenous infusion set. This type of partition design in the recipient hole is well known to those skilled in the art.

 Shown in FIG. 23-29, the construction of the container assembly 300 is similar, as can be seen, to the construction shown in FIG. 17-22. The container assembly, the details of the device of which we will not repeat, is inserted into the cylindrical part of the housing 400 and the plunger 86 initially mates with the connecting element 112 as described above (see also Figs. 32 and 33). In this latter embodiment, the cylindrical portion 400 is bonded to the rear or concave surface 410 of the base member 406 by means of a connecting collar 470 (FIG. 23). Part 400 also includes a transverse support protrusion 471 with a socket 473, on which the connecting element 112 rests, as best seen in FIG. 30. The supporting protrusion 471 has a channel 477 communicating with the channel 124 of the connecting element 114 and with the channels 414 of the base 402 through the hole 415. In the same way, the body of the outlet channel 452 and the body of the needle valve 474 extend at an angle from the rear surface 410 (Figs. 26 and 28 ) It should be noted that the front surface 408 of the base element 406 is provided with a protruding mounting surface 475 surrounding the hole 415 and onto which the filter 434 is attached. A hole 434a is provided on the filter 434, into which the protruding surface 475 enters, so that the fluid can freely flow through the hole 415 between the channel 414 and the camera 432 (Fig. 25).

 When using the device in this fourth form of implementation of the present invention, it is held by one of the sides 418 and, having removed the vial cap and the cap covering the channel of the sterile connecting element 110, the open end of the drug vial 300 is inserted into the open end 401 of the cylindrical portion 400 (FIG. 23). As best seen in FIG. 29 and 30, after entering the drug vial 310 into the open end 401, the thread 314 engages with the first internal thread 403a formed in the cylindrical portion 400. At the same time, the thread 86b will interface with the thread 113 formed on the connecting member 112. Rotation of the bubble clockwise will cause the thread 314 to mate with the first internal thread 403a, and the thread mate 86b of the plunger 86 to the thread 113 of the connecting member 112 as shown in FIG. 30. The teeth 308, made in the shell 312, will also engage with ratchet teeth 405 on the cylindrical part of the housing 400. After pairing the plunger with element 112, the valve valve stem 106 comes into contact with the valve means valve stem 140, causing simultaneous axial movement of the valve means element 137 of the means for regulating the flow rate and the valve element 92 of the means for regulating the flow rate of the container to the open position shown in FIG. 30 and 32. With the flow control valves in this open position, the stretchable membrane 430 will cause the fluid contained in the chamber 432 to flow under pressure through the opening 415 (FIGS. 25 and 30) into channel 477, channel 124, through a valve seat 128 in a fluid channel 126 of connecting means and then into a channel 103 of the valve means of the container. The pressurized fluid then flows into the radial openings 94 of the container valve and immediately afterwards into the interior 309 of the glass container 309 as shown by the arrows in FIG. 30. Such a flow of liquid under pressure into the drug vial will cause a mixing or dilution process.

 As shown by the arrows in FIG. 30, the fluid entering the drug vial will be thoroughly mixed with the drug M contained in the vial in such a way as to obtain an active drug fluid consisting of a mixture of the liquid stored in chamber 432 and the drug M stored in the vial.

 After mixing the drug M with the diluent, the drug vial assembly is rotated again clockwise, as shown in FIG. 31. During this additional rotation, the bubble will move along the circumferential free space 479 made in the cylindrical part 400. As before, the space 479 serves as an intermediate space and is located between the first thread 403a and the thread 403. The presence of the intermediate space 479 gives time for backfilling the system and diluting the drug. Continued clockwise rotation of the drug vial assembly will conjugate thread 314 to thread 403, moving the drug vial assembly from the position shown in FIG. 30 to the stop position shown in FIG. 31. The ratchet teeth 308 on the shell will also mesh with elastic ratchet teeth 405 formed on the inner surface of the housing portion 400, substantially fixing the bubble in position within the housing 400.

 Continued movement of the drug vial assembly to the end position shown in FIG. 31 causes an almost complete return of the diluted mixture back to the infusion system chamber 432 through channels 94, 103, 126, 124, 477 and 414 and through aperture 415 for subsequent controlled infusion to the patient through a filter 434 and a plurality of collection channels for liquid 412 into channel 414 through a hole 417 and further from the device through the channel 452 and the outlet 448. As shown above. the rate of fluid flow through the outlet 448 is controlled by a needle valve 63.

 And in this case, the label covering the peripheral surface of the shell 312 may be marked with numbers, color codes, or the like, in order to indicate the position of the bubble assembly relative to the cylindrical portion 400 when connecting, diluting, and transferring the diluted drug.

 In FIG. 34-38 show the most recent embodiment of the invention. This latter embodiment is in many respects similar to the embodiment shown in FIG. 23-33, and identical numbers are used to designate parts. More specifically, the part with the infusion container of the device along with the connecting elements 112 and 114 are identical to those described previously, as are the valve of the connecting means 136 and the control means. However, the cylindrical portion of the housing 500 mounted on the rear surface 410 of the base 406 has a slightly different construction, as does the drug vial assembly. The structural features of these different elements and the method of application of this latter form of the invention will be described in the following paragraphs.

 Turning first to FIG. 34 and 35, on which you can see the base unit, quite similar to that shown in FIG. 25 and having a curved base element 406 with a plurality of liquid microchannels 412 communicating with a central channel 414 consisting of separate sections 413 and 416. The side sections 418 with openings 420 are similar to those described previously. The device also includes a stretchable elastic membrane 430 and a filtering device, which act in the same way as described previously. In FIG. 36 shows a drug vial or container assembly 502 of the present embodiment comprising second means for controlling the flow of fluid entering and leaving the drug chamber M 59 into the inner chamber 509 of the vial 510. The second flow control means in this embodiment is identical in design and principle to that described above and consists of a low hardness plunger 86 that fits snugly into the bubble 510. The plunger 86 also has connecting means, shown as thread 86b, to interact with connecting means devices. As before, the valve assembly 88 controls the fluid flow passing through the channels made in the plunger 86, and it is controlled by means of a control device of the type described above.

 The bubble 510 is placed in a collection cover, or shell 512, surrounding the bubble 510. The shell 512, in turn, telescopically enters the sleeve 512a, including the locking stop system 511. Closer to the lower end of the sleeve 512a there is an external thread 514 that is compatible with the internal thread 504 in the cylindrical part 503 of the device body. The bubble 510 is closed by a tear-off type integral cap, such as 508 (FIG. 36). The sleeve 512a is also provided with circumferential finger grips 507, the purpose of which will be described below. The shell 512 includes locking means for fixing it to the cylindrical parts of the housing 503. This locking means is in this case in the form of an annular part 515 located closer to the lower end of the element 512.

 In FIG. 37 shows that the cylindrical portion 502 of the housing of the device representing this last embodiment of the invention has an enlarged neck 517, which includes a stop 511 and which has a protruding annular surface 519, which abuts the stop 519. In addition to the surface 519, at a certain distance in the longitudinal direction from it there is an inwardly projecting annular stop 521, which, in the manner described below, is used to complete the cycle by fixing the annular element 515 made on the shell 512.

 In the process of using the device, which is the last form of the invention, first, the cap 508 is removed from the node with the drug vial 300. After that, the open end of the drug vial 502 is inserted into the sterile neck 517 of the cylindrical part 503 (Fig. 37). Using to control the finger protrusions 507, the thread 514 is aligned with the internal thread 504 provided in the cylindrical portion 503. Thereafter, the bubble assembly 502 is advanced to bring the thread 86b on the plunger 86 closer to the thread 113 on the connecting member 112. Further rotation beyond the protrusions for the clockwise fingers 507 of the drug vial will pair the thread 86b on the plunger 86 with the thread 113 on the connecting member 112 as shown in FIG. 37. After the plunger mates with the element 112, the valve valve stem 106 comes into contact with the valve valve means 140 140, causing the first flow control means and the valve element 92 of the second flow control means 92 to open in the axial direction shown in FIG. 37. With the flow control means in the open position of the valves, the stretchable elastic membrane 30 will cause the pressure of the fluid contained in the chamber 432 to flow through the opening 415, into the channel 477, channel 124, through the valve seat 128 into the fluid channel 126 of the connecting means and then into channel 103 of the valve means of the container. The pressurized fluid then enters the radial openings 94 of the container valve and immediately thereafter into the interior of the container 510 as shown by the arrows in FIG. 37. Such a flow of pressurized liquid into the drug vial will cause a mixing or dilution process and will cause the container to shift outward (upward, as shown in FIG. 37).

 In all of the still described embodiments of the invention, the reservoir valve plug is preferably made of rubber or silicone. The valve element reciprocating within the plunger is preferably made of harder rubber or silicone, or glass or plastic, such as polypropylene, polycarbonate, polystyrene, acrylonitrile butadiene copolymer, polytetrafluoroethylene or high-density Teflon or nylon. Similarly, valve member 137 is preferably made of silicone rubber, rubber, flexible polyvinyl chloride, polyurethane, polytetrafluoroethylene, or silicon fluoride elastomers.

 Turning now to FIG. 39-53, which shows another embodiment of the invention. In this embodiment, the construction of the cylindrical part of the body 600 and the base unit 604 is close to the structure of the part of the body 400 and the base unit 406 shown in FIG. 23-28 and the same positions are used to designate the same parts. However, the container assembly, the details of the device of which will be described below, has a slightly different design. More specifically, a device representing this new embodiment of the invention allows for controlled mixing of a diluent or other source liquid with a drug by using flow control means to precisely control the flow of liquid between the storage tank and the drug mixing chambers.

 In this latter embodiment, the cylindrical portion 600 is bonded to the rear or concave surface 410 of the base element by means of a connecting collar 470 (FIG. 23). Part 600 also includes a transverse support protrusion 607 with a socket 609, on which the connecting element 612 rests, as best seen in FIG. 40. At the base 406 there are longitudinal channels 614 and 616. The channel 614 communicates with the reservoir 432 and the hole 415. The channel 616 communicates with an outlet made in the housing of the exhaust channel 472. In the same way, the body of the needle valve 474 of the type described above extends at an angle from the rear surface 410 (FIGS. 26 and 28). It should be noted that the front surface of the base element includes many intersecting microchannels 412 and is provided with a protruding mounting surface 475 surrounding the hole 415 and onto which the filter membrane 434 is attached (Fig. 39). The filter and microchannels 412 act in the same way and are intended for the same purposes as those described above.

 In FIG. 41 and 42 show a container assembly 620 of this embodiment of the invention, consisting of a glass vial 622 with a chamber 624 for containing a medicine, which may be a medicine with a long release period, which is shown here in the form of capsules or tablets 625. A plastic cap or the sheath 626 is tightly mounted on the bubble 622 and includes a measured thread 627 (Fig. 53), the purpose of which will be described below. Around the cover 626 is a sleeve 628 with an external thread 630 and fixing stops 632. The thread 630 mates with an internal thread 634, made on the cylindrical part 600. Inside the ampoule 622 there is a means for regulating the flow of this form of the invention for almost completely regulating the flow of liquid into the mixing chamber 624 and flowing from there. In this case, the flow control means consists of a plunger 636 that fits tightly into the bubble 622. In general, the plunger 636 has a structure similar to that of the previously described plunger 86, cylindrical in shape with a skirt 638 designed for tight contact with the inner wall of the bubble 622 (FIG. . 44).

 A central hole 639 and several fluid channels 640 located around the circumference are made along the axis of the plunger. The fine flow control valve element 642 is also part of the flow control means and includes an inlet channel 643 located on the central axis. Reciprocating movement in the channel 639 and provided with a first flange 641, designed to control the flow of fluid through the channels 640. The element 642 also includes a second, or inner flange 645, guiding the movement paw element in an annular channel 636a, formed in the plunger 636. The valve member 642 also includes a stem 647, which in the manner described below, cooperates with a check valve 646, an internal passageway 649 provided in coupling member 612 (FIG. 43). Stem 647 is an integral part of valve member 642 and terminates at the inner end 647a. Near the opposite end 647b of the rod 647 there is a transverse fluid channel 650, passing fluid through the shutoff valve 646, and then entering the inlet channel 643 (FIG. 50).

 When using the device representing this latest embodiment, the cap 651 closing the vial is first removed and the cap 652 closing the channel, the open end 653 of the drug vial assembly is ready to be inserted at the end 601 of the cylindrical portion 600 (FIG. .45), which in some cases may be closed with a sterile tear-off lid (not shown). As best seen in FIG. 43 and 44, after the drug bubble assembly 620 is inserted into the open end 601 of the device infusion system, the thread 630 will engage with the first internal thread 634a in the cylindrical portion 600. With the fingers gripping the protrusions 654 of the sleeve 628, you can rotate the bubble with the drug clockwise, causing the drug bubble in the cylindrical portion 600 to advance to the position shown in FIG. 45. In this fixed position, the retainers of the system 632 advance to an internal stop 655 formed in the cylindrical portion of the housing 600. When the drug vial is thus aligned with the cylindrical portion 600, the valve stem 647 642 will advance to the shutoff valve 646.

 In FIG. 45, it can be seen that clockwise rotation of the bubble 620 relative to the sleeve 628 will cause the stem 644 to abut against the shutoff valve 646. Since the pressure of the fluid in the reservoir acts on the valve 646, moving the shutoff valve to the open position will encounter resistance. Accordingly, control valve 642 will shift to the left to the position shown in FIG. 45. However, when the flange 645 abuts against the shoulder 636a of the plunger 636, continued clockwise rotation of the bubble in the sleeve 628 will cause the stem 644 to slide the shutoff valve 646 to the left to the open position shown in FIG. 45. With the shutoff valve of the flow control means in the open position, the expandable membrane 430 will force the fluid in the chamber 432 to flow under pressure through aperture 415 (FIGS. 40 and 45) into channel 658, then into channel 660 through the valve seat 662 into the fluid channel 664 of the connecting element and then into the central channel 643 of the inlet valve element 642. Then, the liquid under pressure will quickly enter the drug chamber of the glass container as shown by the arrows in FIG. 45. This pressurized fluid stream entering chamber 624 causes a controlled flow of diluent around the capsules 625 and the beginning of a controlled mixing or dilution process to produce a therapeutic substance for infusion to the patient.

 Referring to FIG. 45, it can be noted that the rotation of the bubble 620 relative to the sleeve 628 not only leads to the opening of the shutoff valve 640, but also causes the flange 641, including the protrusions 641a of the element 642, to move from the position shown in FIG. 44, in which the flow of fluid through the channels 640 of the plunger 636 is blocked to the open position shown in FIG. 45. This movement of valve 642 to the right, as shown in FIG. 45, allows fluid to flow back from the drug chamber 624 into the channels 640 of the plunger 636, as shown by arrows 665 in FIG. 45.

 If the valve member 642 is in the position shown in FIG. 45, the mixed solution, or therapeutic substance, will continue to flow under pressure through channels 640, into channels 668 made in connecting element 612, into an annular collecting channel 670 (Fig. 47), into channel 672 made in cylindrical part 600, and then to the outlet through channel 452. In the chamber with drugs 624 there is a filter 674 that traps solid particles before releasing the diluted therapeutic substance from the device.

 After the controlled mixing of the drug with the diluent has begun, the intensity of the flow of diluent from the reservoir 432 into the drug vial and back into the reservoir can be precisely controlled by rotating the drug vial counterclockwise relative to the measured thread 677 made on the sleeve 628 as shown in FIG. 48. This rotation of the bubble counterclockwise, as shown in FIG. 48 causes the shutoff valve 646 to move toward the closed position shown in FIG. 48, with a decrease in fluid flow towards the mixing chamber. In this way, fluid flow can be precisely controlled in the direction of the mixing chamber 624. With regard to FIG. 47 and 51, it should be noted that along the circumference of the surface of the shell of the bubble 626 there are many grooves 630, while on the sleeve 628 there is a tooth 682 protruding radially inwardly inward. As the bubble rotates relative to the sleeve, the tooth 682 will sequentially fall into the furrows, causing a click and allowing very precise control of rotation. As shown in FIG. 41, the shell 628 is provided with an arrow 684, indicated on a scale 686, which can be color coded and determine the flow rate corresponding to a given position of the ampoule relative to the sleeve. Ratchet teeth may also be formed on the shell, engaging with elastic ratchet teeth on the inner wall of the cylindrical portion of the housing 600 so as to substantially immobilize the sleeve 628 in the portion of the housing 600 while adjusting the flow rate.

 In FIG. 52-62 shows another embodiment of the invention. In this embodiment, the design of the infusion system of the device, including the cylindrical part of the housing and the base unit, is identical to the design in the embodiment of the invention shown in FIG. 39-51, and the same reference numbers are used to indicate identical parts. However, in this case, the container assembly, the details of the device of which will be described below, has a slightly different design. As with the embodiment shown in FIG. 39-51, a device representing this latter embodiment of the invention also allows unique mixing capabilities of a diluent or other source liquid with the drug by using flow control means to precisely control the flow of liquid between the storage tank and the drug mixing chambers.

 In FIG. 52 and 53, an assembly of a container 720 of this embodiment of the invention is shown, consisting of a glass vial 722 with a chamber 724 for containing a medicine, which is shown here as a soluble drug 725. The plastic cap or shell 726 is tightly worn on the vial 722 and includes a thread 727 (FIG. 53), the purpose of which will be described below. Around the cover 726 is a sleeve 728 with an external thread 730 and locking stops 732. The thread 730 mates with an internal thread 634, made on the cylindrical part 600 (Fig. 55). Inside the bubble 722, a flow control device of this last form of the invention, having a slightly different configuration, is located for almost completely controlling the flow of liquid entering and leaving the mixing chamber 724. In this case, the flow control means consists of a plunger 736 that fits tightly into the bubble 722. In general, the plunger 736 has a structure similar to that of the previously described plunger 86, cylindrical in shape with a skirt 738 designed for tight contact with the inner wall of the bubble 722 (FIG. 55).

 A central hole 739 and several circumferentially arranged fluid channels 740 are provided along the axis of the plunger 736. The valve for fine flow control 742 has a slightly different device and also forms part of the flow control device. The element 742 performs reciprocating movements in the channel 739 and is provided with a first flange 741 designed to control the flow of fluid through the channels 740. The element 742 also includes a second or internal flange 745 directing the movement of the valve element in the annular channel 736a made in the plunger 736. The valve element 742 also includes a rod 747, which is located in the Central channel 742a and which, in the manner described below, interacts with a check valve 746 located in the internal channel 749, made in flax element 616 (FIG. 55). Stem 747 is an integral part of valve element 742 and terminates at the inner end 747a (see also FIG. 61). Near the opposite end of the stem 747 is a portion with an enlarged diameter 747b, ending with the previously indicated flange 741. Through the portion 747b there are angled circumferential fluid channels 750, which, as described below, allow the fluid to pass through the shutoff valve 746 and enter the chamber 724 (Fig. 56). In part of the enlarged diameter 747b, there are also circumferentially located radially directed holes 742b.

 When using a device representing this latest embodiment of the invention, the cap 651 closing the vial and the cap 652 closing the channel of the drug vial are first removed (Figs. 54 and 55). After that, the open end 753 of the drug vial assembly is ready to be inserted at the end 601 of the cylindrical portion 600, which in some cases may be closed with a sterile tear-off lid (not shown) (FIG. 54). As best seen in FIG. 54 and 55, after the drug vial assembly is inserted into the open end 601 of the device infusion system, the thread 730 will engage with the first internal thread 634a in the cylindrical portion 600. By gripping the protrusions 754 of the sleeve 728 with your fingers, you can rotate the vials with the drugs clockwise, causing the drug vial in the cylindrical portion 600 to advance to the position shown in FIG. 55. In this position, the latches of the system 632 will advance to the internal stop 655 made in the cylindrical part of the housing 600. When the drug vial is thus aligned with the cylindrical part 600, the valve stem 747 742 will advance to the shut-off valve 746.

In FIG. 56, it can be seen that rotating the bubble 720 clockwise with respect to the sleeve 728 will cause the stem 747 to abut against the shutoff valve 746. Since the pressure of the fluid in the reservoir acts on the valve 646, the control valve 742 will shift to the left to the position shown
in FIG. 56. However, when the flange 745 abuts the shoulder 736a of the plunger 736, continued rotation of the bubble 720 clockwise in the sleeve 728 will cause the stem 747 to slide the shut-off valve 746 to the left to the open position shown in FIG. 56. With the shutoff valve of the flow control means in the open position, the expandable membrane 430 will force the fluid in the chamber 432 to flow under pressure through aperture 415 (FIGS. 40 and 46) into channel 658, then into channel 660 through the valve seat 762 into the fluid channel 664 of the connecting element and then into the central channel 742a of the intake or control valve element 742. Then, the liquid will enter the channels 742b and 750, after which it will quickly enter the mixing chamber 724 (see also Figs. 59 and 60). This pressurized fluid flow entering chamber 724 causes a controlled flow of diluent around the drug 725, as shown in FIG. 56, and the beginning of a controlled process of mixing or dilution in order to obtain a useful agent intended for infusion to the patient.

 Referring to FIG. 55, it can be noted that as long as the valve element 742 is in the position shown in the figure, the flange 741, including the protrusions 741a formed thereon, will prevent fluid from flowing through the channels 740 in the plunger 736. However, as mentioned above, rotation of the bubble assembly 720 in the shell 726 will cause the valve element 724 to shift to the right under the influence of the shutoff valve 746. While the element 742 is in the position shown in FIG. 56, the mixed solution, or useful agent, will continue to flow under pressure in the opposite direction to the reservoir 432 through channels 740, into channels 668 made in the connecting element 612, into the annular collecting channel 670 (Fig. 49), into the channel 672 made in the cylindrical part 600, and from there to the reservoir 432. As before, in the chamber with medicines 724 there is a filter 774 that traps solid particles before releasing the diluted useful agent from the device.

 After the controlled mixing of the drug 725 with the diluent begins, the intensity of the flow of the diluent from the reservoir 432 into the mixing chamber of the drug vial and back from the device can be precisely controlled by rotating the drug vial counterclockwise relative to the 777 thread made on sleeve 728 so as described above and shown in FIG. 58.

 As shown in FIG. 62, mixing chamber 747 contains a drug in the form of a soluble tablet 725a. Such a tablet includes a medicament, such as a muscle relaxant.

 In FIG. 63-67 show another embodiment of the invention. In this embodiment, the construction of the cylindrical portion of the housing 800 and the base unit 804 is similar to the construction of the portion of the housing 400 and base unit 406 shown in FIG. 23-28, and the same reference numbers are used to indicate identical parts. However, in this case, the container assembly, the details of the device of which will be described below, has a slightly different design. A more specific device representing this latter embodiment of the invention also allows unique mixing capabilities of the first component, such as a diluent, diluent, or other parenteral liquid, with an additive, such as a drug or other therapeutic material, that is introduced into the first component by using unique means making additives such as those described below.

In the following paragraphs, which will examine in detail this unique mixing process, the following terms will have the following meanings:
Element - any of the basic substances, which consists of atoms of only one species and which alone or in combination forms all the material.

 Additive - an element, compound, substance, reagent, biologically active material or other material that must be added, in whole or in part, to the liquid introduced into the device that is the subject of the invention.

 A polymer is a chemical compound or mixture of compounds formed by polymerization and consisting mainly of repeating structural units.

 Parenteral fluid is any solution that can be administered to a patient in addition to the gastrointestinal tract, including water, saline solutions, alkaline solutions, dextrose solutions, acidifying solutions, electrolyte solutions, reagents, solvents and the like aqueous solutions.

 Useful means - any medicine, medication, pharmaceutical, medical polymers, enzymes, hormones, antibodies, element, chemical compound or other material used in the diagnosis, treatment, to mitigate, cure or prevent the disease, as well as maintaining good health of the patient.

 Biologically active material - a substance with biochemical, immunochemical, physiological or pharmaceutical activity or reactivity. A biologically active material includes at least one or more of the following substances: biochemical compounds (such as amino acids, hydrocarbons, lipids, nucleic acids, proteins and other biochemical and other substances that can combine or interact with biochemical compounds), such biochemical compounds biologically act such as antibodies, antigenic substances, enzymes, cofactors, inhibitors, lectins, hormones, hormone-forming cells, receptors, coagulation factors, stimulators of po that, histones, peptides, vitamins, pharmaceuticals, surface markers and toxins, among others known to those skilled in the art. Of the group of biologically active materials, the most interesting in this case are proteins with large molecules obtained by biopharmaceuticals by genetic engineering methods, as those species that need to be fixed and collected on additive carriers, which will be described below. A description of the use of biomosaic polymers as carriers of biologically active materials is given in patent application 04330517 A2.

 Additives - additives and any means for introducing an additive into a fluid flowing through fluid channels in a fluid delivery device of the present invention so that all or any portion of the additive is introduced into the fluid. Additives include additives and additives, which may take the form of a functional carrier, anchorage, deposition or reaction or material to hold elements with or without a particular type of intermediate base, as well as another type of additive release agent.

 Additives - any means, like functional carriers or substrates, designed to add additives to a fluid flowing through a device. The functional carrier can be made of a polymer, copolymer, ceramic, crystalline sponge, carbon base, cellulose, glass, plastic, biomosaic polymers, azlactone granules - a functional polymer, adduct product granules, carboxylate functional polymer granules, resins, gels, threads and the like carriers.

 The adding agents in the present invention may take any form similar to those shown in FIG. 66. However, in a preferred embodiment, the addition agents include a cylindrical-shaped microporous polymer carrier which is located in the mixing chamber of the container assembly and to which various additives, including useful agents such as drugs, biologically active materials, and chemical agents, can be subsequently separated. substances and elements. These additives are placed in the structure such that as a liquid, such as a diluent, reagent or other aqueous solvent, flows around or through the carrier as shown by the arrows in FIG. 64, additives enter the fluid stream and are easily released and added to the liquid as it flows through the chamber in which the adding agents are placed.

 The additives themselves can also take various physical forms, including the form of a liquid, solid material, granules, powder, particles, gel, wax, hydrocolloid carrier, resin, film, tablets, crystals, emulsions, microcrystals, microspheres, spray dried and lyophilized compounds and saturated substances. Additives may be loosely bound, applied, or otherwise bound to carriers, carriers may be impregnated with them in a variety of ways. Additives can be attached chemically or mechanically, attached or directly or indirectly linked through an intermediate base. They can be trapped, attached, bound or cross-linked, fixed to the surface of the carrier or surface active agent, or they can be absorbed, bound by the catalysis reaction, electrostatically sealed, by chemical modification bound to the surface of the carrier, polymerized on the carrier or by its thickness, localized, captured, precipitated, weighed or occluded in the pores, cells, tubes or voids formed in the carrier. One important method of attachment, followed by isolation of additives to the functional carrier, comprises treating the functional carrier with a compound comprising active functional groups, such as aelactone functional compounds with their higher binding ability. In some cases, biologically active material may be applied to the surface of biomosaic polymers by the method described in patent EP WO N 0430517 A2. In a similar manner to the method described in US Pat. No. 5,013,795 to Coleman et al., Graft copolymers can be used. Thus, complexing agents, catalysts, and biological materials such as enzymes or other proteins can be attached to the carrier.

 Similarly, additives can be immediately separated from the functional carrier and added to the liquid flowing through the device, or mixed with it in one or more of a variety of ways, including chemical reaction, dilution, separation, displacement, bioseparation, diffusion, washing, disintegration, erosion, isolation desorption, dissolution, leaching, digestion of enzymes, biological reactions, osmosis, separation from materials with ring opening by ring opening and the like separation methods.

 In FIG. 66, various forms of added agents or additive carriers are shown. These additive carriers are housed within the container assembly of the invention, the construction of which will be described below.

 As best seen in FIG. 63 and 64, in this last form of the invention, the cylindrical portion 800 is bonded to the rear or concave surface 410 of the base element by means of a connecting collar 470 (FIG. 23). Part 800 also includes a transverse support protrusion 807 with a socket 809, on which the connecting element 812 rests, as best seen in FIG. 40 and 64. At the base 806, longitudinal channels 814 and 816 are made. Channel 814 communicates with the reservoir 832 and with the hole 815. Channel 814 communicates with the outlet of the device in the housing of the outlet channel 872. This channel can also be used for aseptic pre-filling reservoir in the manufacturing process of the device. Likewise, the housing of a needle valve 874 of the type described above extends at an angle from the rear surface 410 (see also Figs. 26 and 28) and includes a second flow control means according to the invention for regulating a fluid flow. It should be noted that on the front surface of the base element there are many intersecting microchannels 812 and there is a protruding mounting surface 875 surrounding the hole 815 on which the filter membrane 834 is attached (Fig. 63). The filter and microchannels 812 act in the same way to achieve the same result as described above.

 In FIG. 64 shows a container assembly 820 of this embodiment of the invention, consisting of a glass bubble 822 with a channel for fluid to flow through it and walls forming a mixing chamber 824 in communication with the liquid channel. Chamber 824 serves in this last form of the invention to place additives therein. A two-part plastic cover or shell 826 is tightly fitted to the bubble 822. The cover 826 includes first and second parts 826a and 826b. Part 826a is provided with an external thread 830 and locking stops 831. The thread 830 mates with an internal thread 834 made on a cylindrical part 800 (FIG. 64). Inside the bubble 822, there is placed the first flow control means of this last form of the invention for almost completely controlling the flow rate of the liquid entering and leaving the mixing chamber 824. In this case, the flow control means consists of a plunger 836 that fits tightly into the bubble 822. In general, the plunger 836 has a structure similar to that of the previously described plunger 86, cylindrical in shape with a skirt 838 designed for tight contact with the inner wall of the ampoule 822 (FIG. .64).

 Along the axis of the plunger 836, a central hole 839 and several circumferentially arranged fluid channels 840 are formed. The valve element for fine flow control is also part of the flow control means. The element 842 performs reciprocating movements in the channel 839 and is provided with a first flange 841 designed to control the flow of fluid through the channels 840. The element 842 also includes a second or internal flange 845 directing the movement of the valve element in the annular channel 836a made in the plunger 836. The valve element 842 also includes a stem 847, which is located in the central channel 842a and which, in the manner described below, interacts with a stop valve 846 located in the internal channel 849, made in flax member 812 (FIG. 64). Stem 847 is an integral part of valve member 842 and terminates at the inner end 847a (see also FIG. 65). Near the opposite end of the stem 847 there is a portion with an enlarged diameter 847b ending in the previously indicated flange 841. Through the portion 847b there are angled circumferential fluid channels 850, which, as described below, allow the fluid to pass through the shut-off valve 846 and enter the chamber 824 through channel 850.

 When using a device representing this latest form of the invention, the cap 851 that closes the bubble and the cap that closes the socket or open channel 809 of the cylindrical portion 800 (not shown) are first removed. After that, the open end of the drug vial assembly is ready to be inserted into the open end 809 of the cylindrical portion 800. After the drug vial assembly is inserted into the open end 809 of the device infusion system, the thread 830 will mesh with the first internal thread 834a formed in the cylindrical part 800. The clockwise rotation of the drug vial causes the drug vial in the cylindrical part 800 to move to a position where the rod 847 to closes shut-off valve 846. Since pressurized fluid in the reservoir prevents the shut-off valve from moving, control valve 842 will shift to the left. However, when the flange 845 abuts against the internal stop 836a of the plunger 836, continued rotation of the bubble 820 clockwise will cause the stem 847 to slide the shutoff valve 846 to the left to the open position shown in FIG. 64. With the shutoff valve open, the stretchable elastomeric membrane 430 will cause the fluid in the reservoir 832 to flow under pressure through the bore 858a into the channel 858, through the valve seat 862 and into the fluid channel 846b of the connecting member. After that, the liquid will enter the channel 850 and after that it will quickly pour into the mixing chamber 824 through the central channel for the liquid 850a, made in the added means. This pressurized fluid stream entering chamber 824 will result in a controlled flow of the first component, such as a diluent, through and around the adding agents.

 Turning in particular to FIG. 64, it should be noted that while the valve element 842 is in the position shown, the mixed or dosed solution will continue to flow under pressure in the opposite direction through channels 840, into channels 868 made in the connecting element 812 and into the annular channel 870. From the channel 870 is liquid enters the channel 87, made in the cylindrical part 800 and from there to the outlet of the device for the purpose of controlled delivery.

 It is important to recognize that in added agents in this embodiment of the invention, carriers may be provided with an affinity base, binding ability allowing for highly effective, biospecific bonding of additives to the base in significant quantities. A significant part of the additives can subsequently be efficiently released immediately or, in another embodiment, over a long period of time, thus providing a controlled infusion in the regimen most therapeutically favorable for the patient. Additionally, the kinetics of the detachment reaction for desorption of the absorbed component from the affinity base can be set so as to fully determine the optimal conditions for the elution of the associated additives. A suitable eluting diluent acts as a desorption agent which, over a period of time, disrupts the affinity bonds. In this embodiment, the use of different designs of the node of the vial with the drug with a varying intensity of drug release allows you to set the rate of diluent flow regardless of the specified dosage (disconnecting, separating or isolating the additive from the carrier with the activated substrate). In this way, the possibilities of selective dosing and flow rates can be optimized depending on the physiological characteristics of a particular patient.

 As shown in FIG. 64, adding agents housed in mixing chamber 824 are presented here in the form of a cylindrical, functional supporting structure or carrier to which various additives may be freely connected, including useful agents such as drugs, biologically active materials, as well as chemical elements and connections. These additives are placed on the supporting structures so that when fluid flows through the chamber 824 and circulates around the carrier, as shown in FIG. 64, additives will enter the fluid stream and gradually be added to the liquid as it flows through the chamber. On each side of the carrier 877 are distribution plates of glass solder (Fig. 65), designed to evenly distribute the fluid flow at the inlet and outlet of the chamber.

 In addition to the means of introducing additives discussed above, the use of a polymer is also possible as a carrier or base for the placement of additives. Three types of polymer carriers can be used, namely: polymer reagents, polymer catalysts and polymer substrates. An analysis of polymers as carriers or bases is given in: George Odian Principles of Polymerization, second edition. The use of microporous polymers as carriers is also described fully in US Pat. No. 4,591,909 to Castro.

 The second component, such as a parenteral liquid, or an eluting agent entering chamber 824, may include, for example, a reagent, a solvent, a sterile diluent, various electrolytes, aqueous solutions, such as an aqueous dextrose solution, saline solutions, alkalizing solutions, acidifying solutions, polar solutions and any other liquids that may serve as suitable carriers for the administration of therapeutic or beneficial agents that it is desirable to administer to the patient by infusion.

 Turning now to FIG. 66, which shows various other forms of adding agents. So, for example, reference numeral 880 denotes a node made of an insoluble, polystyrene porous substrate with an axially extending fluid channel 881 and interconnected voids 880a, among which one or more emitted additives are placed. Certain additives, such as elements, chemicals, drugs, and functional intermediates, are applied to voids or to a substrate by methods well known to those skilled in the art. Additives enter, of course, an elution reagent, such as a sterile diluent, when the diluent flows around and through substrate 880.

 Another form of the additive assembly indicated in FIG. 66, position 882, is made of an insulated pore substrate having an internal axially extending fluid channel 883. In the pores of this substrate of variable sizes, excreted additives, such as gradually released chemicals and therapeutic substances or medicines, are placed.

 Another form of additive assembly is indicated in FIG. 66 at 884. This assembly is represented by a cylindrical, porous cork-like element made of a plurality of fused microspheres or balls 884a, each of which is coated with a release or reactive coating with an additive deposited thereon, such as a biologically active material or other useful agent. The microspheres forming the internal channels can be made of glass, plastic or other suitable materials.

 Reference numeral 886 in FIG. 66, another form of the inventive adding agent is indicated. In this embodiment, a functional carrier having a generally cylindrical shape serves to attach an affinity based additive and subsequently isolate it. The carrier 886 has an axial channel 887 for liquid and is made of many microporous polymers, representing many reaction points over a wide area, used to bind isotopes.

 The additive assembly shown in FIG. 66, at 888, is represented by a continuous tubular product with an axial fluid channel 889. The outer surface of the product using an acceptable method, including intersurface polymerization using a copolymer, is coated with a specific additive.

 In addition, article 888 can be made from an ion exchange resin to which an additive, such as a drug, can be coupled to form a complex compound of the drug and a resin of the type allowing subsequent gradual release of the drug under the influence of a suitable eluting fluid.

 Another, slightly more complex additive assembly is indicated at 890. This assembly is made up of several separate porous cork-like plates 890a, 890b, 890c and 890d, each plate having the same or different structure and porosity and each has reaction points at which specially selected additives, such as useful agents, elements or compounds, are introduced into the fluid stream, so that multiple reactivity and selectivity can be achieved. With this design, it is possible to achieve a wide variety in terms of liquid flow rate and complex sequential separation with a phased priority introduction of material at the system outlet due to the targeted selection of each plate, which together form a structural support.

 Another form of the additive assembly is the assembly indicated in FIG. 66 at 892. This assembly is a cylindrical structure made up of a plurality of elongated fiber elements 892a, at least some of which are coated, filled or impregnated with certain additives and, if necessary, functional intermediates.

 The functional support element, indicated at 894, is an example of yet another form of adding agent in the present invention. This element, also having a generally cylindrical shape, is made of many separate layers, such as polymer films 894a, to which certain releasable additives and intermediate compounds are connected by affinity.

 The functional carrier 896 is made of a plurality of glass, spaghetti-like filaments 896a, forming a spongy structure with open pores interconnected by meandering intermediate channels. In some or all open pores, a specific additive or necessary additives are placed.

 The functional support element 898 is made of foam that effectively functions as an additive carrier.

 It should be remembered that carriers in another form, such as gels, biomosaic polymers and other porous forms of polymer reaction carriers, including combined azlactone-functional materials, such as foams or polymer granules suitable for bonding with functional materials, can be placed in mixing chamber 824 .

 Knots from 880 to 898, which may be soluble or insoluble, hydrophilic or hydrophobic, are intended to simply serve as an example, without limiting the wide variety of materials and structures that can be used to introduce the necessary additives into the liquid flow entering the mixing device camera.

 As mentioned above, the additives can be combined, if possible, for subsequent isolation with the base or functional carrier in various ways, including the process of chemical modification of the base. One important way of combining the affinity of the additives, if possible for their subsequent isolation, allows the use of a special separation technique, in the broad sense denoted by the term chromatography. In this case, the term chromatography refers to a group of separation methods that differ in the distribution of molecules intended for separation between two phases, one of which is stationary and one is mobile. Affinity chromatography involves the use of biological interactions and involves the use of affinity chromatography vehicles through which the eluting fluid flows. In the present embodiment, the various additive delivery agents, as described herein, may take the form of an affinity chromatography carrier to which various ligands are coupled. In practice, using affinity chromatography methods, one of the components of the interaction pair, the ligand, binds to the solid phase, while the other, the anti-ligand (most often protein), is absorbed from the extract passing through the substrate during the production process. It is important to note that affinity chromatography methods may include the use of highly versatile azlactone functional compounds, such as azlactone functional granules, such as the use of a wide variety of other agents for chemical activation and interaction. Examples of ligands that can be associated with affinity carriers include antibodies, enzymes, lectins, nucleic acids, hormones, and vitamins. Examples of important anti-ligands are antigens, viruses, cells, cell surface receptors, and the like. The methods of chromatography and affinity chromatography are described in detail in the work of Janson aud Ryden, Protein Purification, 1989, and in order to understand these methods well, one should turn to this work.

 Polymer azlactones are well known in the art. Their use in the manufacture of homopolymers and copolymers is described in a number of patents. You can specify as an example, US patent N 3488327 (issued by F. Kolinsky et al. January 6, 1970); US patent N 3583950 (issued by F. Kolinsky et al. June 8, 1971); U.S. Patent No. 4,304,705 (issued to S.M. Heilman et al. December 8, 1981); US patent N 4737560 (issued to S.M. Heilman et al. April 12, 1988) and US patent N 5013795 (issued to Coleman et al. May 7, 1991).

 Azlactones, or oxazolones, are cyclic anhydrides of N-acylamino acids and are used exclusively in organic synthesis. The formation of five-membered azlactone, which has particularly high functional utility for binding, can be achieved through the reaction of the carboxyl group with a-methylalanine through a two-step process (see Immobilized Affinity Ligand Techniques-Hermanson, Mallia and Smith, 1992). One method of forming azlatone granules, the use of which was mentioned above, leads to the use of this process in the polymerization of monomers to first obtain a carboxyl group. In the second stage, under anhydrous conditions, an azlactone ring is formed using a cyclization catalyst. Suitable cyclization reagents to facilitate this reaction include acetic anhydride, alkyl chloroformates, and carbon diimides. The process of forming these active groups and preparing the containing polymeric carriers in the form of granules is described in detail in patents owned by ZM Corporation (US Pat. Nos. 4,871,824 and 4,737,560). These carrier materials are currently offered under the brand name Emphase. US Pat. Nos. 5,045,615 and 5013795, allotted to ZM, also describe recent advances in this technology.

 As indicated in ZM Corporation, U.S. Patent No. 4,737,560, azalkone and functional polymer beads are a useful reaction carrier for attaching functional materials to form new attached beads. The attached granules may be useful as complexing agents, catalysts, reagents and as carriers of enzymes or other proteins. The term “carrier” or “affinity carrier” is usually applied in this sense to a combination of (1) a ligand (usually with a certain known molecular structure) tightly bound (i.e., fixed) by an often covalent bond, and (2 ) bases (usually solid insoluble matter), the materials of the azlactone base of the carrier and the chemistry of addition are also of special interest in connection with the achievable surface area of the base and the effective density of the ligand that can be deposited on this surface.

 US Pat. No. 4,072,566, issued to Lynn on February 7, 1978, entitled "Bound Biologically Active Proteins", describes a method for fixing enzymes or other biologically active proteins to an inorganic carrier material using p-phenylenediamine. Carrier materials whose use according to the invention is considered useful include siliceous materials, tin dioxide, titanium dioxide, manganese dioxide and zirconium dioxide.

 The structure of the functional carrier 877 in the present embodiment of the present invention may have the nature of an affinity carrier and provide for the possibility of binding to the carrier of enzymes or other biologically active proteins followed by separation. This is achieved by treating functional carrier 877 with a compound comprising certain active functional groups, such as azlactone functional compounds, in the manner described in the previously issued patents listed in the previous paragraphs. In this way, complexing agents, catalysts, and biological materials, such as enzymes, proteins, or other affinity scavengers, can be coupled to a carrier for subsequent isolation and use.

 With the addition of some biologically active proteins and other macromolecules, the use of “legs” or harnesses proved to be very useful. “Feet” or bindings are low molecular weight molecules that are used as intermediates between the support material and the affinity ligand. Typically, the "legs" are composed of normal hydrocarbon chains with functional groups at both ends for their connection with the base and ligand. Firstly, one end of the leash is chemically bonded to the base using the usual fixation chemistry; then the other end connects to the ligand using a secondary coupling procedure. The result is a fixed ligand, which adheres to the main chain of the base at a distance equal to the length of the selected “legs”.

 In FIG. 66A, 66B, 66C, and 66D schematically illustrate the use of “legs” to attach proteins and enzymes to a carrier. The main advantage of using "legs" is that it provides access of the ligand to the binding site of the selected molecule. When the target molecule is a protein and the binding site is under its outer surface, it is necessary to have a “leg” in order to push the ligand far enough away from the base to achieve interaction. As shown in FIG. 66A, when the binding site S is deep or located in a pocket directly below the surface of protein P, the ligand L, which is located either below the surface of the carrier material (upper figure), or the ligand L-1, located directly on the surface (middle figure), cannot reach the level of S binding site on the approaching protein molecule. The result may be a weakened interaction or a complete lack of communication. Accordingly, in these cases, in order to ensure access of the L-2 ligand to the binding site of the protein molecule, a “leg” 899 is required (bottom figure of Fig. 66A). Details regarding the use of “legs” are fully described in section 3.1.1 of the aforementioned work entitled Immobilizes Affinity Ligand techniques. This section 3.1.1 is included here as an analogue.

 Turning to FIG. 66B, 66C and 66D, it should be noted that protein A can be used to bind the antibody molecule due to the natural affinity of protein A for immunoglobulins. Incubation of the antibody with protein A matrix will lead to the attachment of the antibody in the Fe region, outside the antigen binding sites. Subsequent cross-linking of this complex with DMP (dimethylpimelimidate) results in a covalently coupled antibody with antigen binding sites facing outward and open to interaction with the antigen.

 With rigid carrier materials, the binding molecule also provides greater flexibility, allowing the attached ligand to reach a position that provides the correct orientation of binding to the protein. The degrees of freedom that a hydrocarbon extender can give are far greater than the possibilities of movement in the backbone of the base polymer.

 The choice of the “leg” molecule may affect the relative hydrophilicity of the immediate environment of the attached ligand. Molecules containing long hydrocarbon chains can increase the potential for nonspecific hydrophobic interactions, especially when the affinity ligand is small and has a small molecular weight. The choice of "legs" with more polar components, such as secondary amines, amide bonds, ether groups or hydroxyls, will minimize the hydrophobic effect.

 It is also important to consider the possible ionic effect of the “leg” molecule on the gel. The “legs” with terminal groups of primary amines must be fully compatible with the ligand or blocked by an inappropriate molecule (eg acetic anhydride; see section 3.1.1.9 in Immobilized Affinity Ligand Techniques) to avoid the possibility of a positive charge on the carrier. With small ligands, these residual charges can form a secondary environment, which can lead to significant non-specific interactions with proteins. This is also true for "legs" with terminal carboxyl groups. In general, a “leg” with a negative charge causes less nonspecific protein binding than a “leg” with a positive charge, however blocking excess remaining groups is still a good idea. A good blocking reagent for use with carboxy residues is ethanolamine, which leaves a terminal carboxyl group (see Immobilized Affinity Ligand Techiques for a more detailed analysis of the types of legs and various attachment and combination protocols).

As indicated in Janson and Ryden Protein Purification, 1989, in which p. 3109 describes one of the alternative forms of protein attachment:
"The interaction of the ligand and protein is often based on a combination of electrostatic, hydrophobic and hydrogen bonds. Reagents that weaken such interactions can be expected to act as effective non-specific eluents."

 This work provides an additional description of the methods described here.

 The above work also discusses three important areas of chromatography applicable to the present invention, namely isocratic elution, gradient elution, and size exclusion chromatography.

 In FIG. 67-70 shows another embodiment of the invention. In this embodiment, the construction of the cylindrical part of the housing 900 and the base unit 901 is similar to the construction of these components in the last considered embodiment of the invention and the same parts are denoted by the same positions. However, the last form of the invention is characterized in that the fixed drug is contained in its own node with the bubble 902, and the liquid component, or parenteral liquid, is contained in a separate node 904, which can be interfaced with the node of the bubble and with the cylindrical part of the housing for mixing the drug with a liquid component, followed by loading into the tank by stretching the energy source or stretchable membrane 430 in a manner that will be described in more detail below. Similar to the device described above, this embodiment of the invention allows for controlled mixing of the first liquid component with the second component or additive, such as a drug or beneficial agent, which is introduced into the first component by the special additive means described in the previous section of the present description.

 As can be clearly seen in FIG. 67, in this last embodiment of the invention, the cylindrical portion 900 is connected integrally with the rear or concave surface 410 of the base element by means of connecting collars 410a. Part 900 also includes a laterally extending wall 906 with a socket 907, within which the nodes 902 and 906 are arranged in the manner best seen in FIG. 68 and 69. In the lower part 908 (FIG. 68) there is a longitudinal channel 909, which communicates with the reservoir 910 as shown in FIG. 69. The outlet of the device communicates with the reservoir 910 through the channel 872, the design and placement of which are not similar to those described previously.

 As shown in FIG. 67, the needle valve body 874 of the type described previously extends outwardly from the rear surface 410 (see also FIGS. 26 and 28). The needle valve 874a is housed in the housing 874 and acts as previously described with a cap 874b securing the adjusting end of the valve. It should also be noted that on the front surface of the base element there are also many intersecting microchannels 812 communicating with the hole 815 onto which the filter membrane 834 is adhered, the filtering means and microchannels 812 act in the same way to obtain the same result as previously described.

 Referring to FIG. 68 and 69, the fluid bubble assembly 904 consists of a bubble 912 with a chamber 914 for receiving a liquid component, such as diluent D. A bubble cap 912 is tightly attached to the bubble 912. The cap 915 is provided with an external thread 916 and clips 917 (FIG. 67). The thread 916 mates with the first and second longitudinally spaced portions of the internal thread 918a and 918b, made in the cylindrical part of the housing 900. Below, we will consider the method of interaction of the bubble with the liquid and the housing.

 The open end of the bubble 912 is closed by a sealed cap or stopper 920, in the center of which a cannula with a blunt tip 921 is tightly inserted, providing communication between the chamber 914 containing the liquid component or diluent D and the outer part of the bubble assembly. For purposes that will become apparent from the foregoing, plug 920 may move in chamber 914 from a first position near the open end of the bubble to a second position near the deaf end. Prior to use, the open end of the bubble 912 and the cannula 921 are closed by a standard type tear-off lid 912a (FIG. 67).

 The drug vial assembly 902 includes a glass vial 922 with an internal thread 923 and a chamber 924. The chamber 924 is closed at one end by an elastomeric stopper 925, which is held in place by a crimped cap that fits snugly against the vial 922 (Fig. 68). The opposite end of the female thread chamber 924 is also sealed with an elastomeric sealed plug 926 that the cannula 927 with a blunt end should be stitched, centrally located in the shut-off valve body 930 located in the chamber 931 located at the base 908. The cannula 927 provides communication between the camera 924 and a fluid channel 928 passing through the shut-off valve body and communicating with the reservoir 910 through the channel 909 when the shut-off valve 932 is open. The shut-off valve 932 is guided along circumferential slots or ribs 912a. Below is a description of the operation of the shutoff valve 932 in the process of filling the tank 910.

 Next to the stoppers 925 and 926 are distribution round disks made of porous glass 933 and 934, which are intended for the proper regulation and distribution of the eluting diluent flowing through the addition means of the present invention and located between the distribution disks. Additives in the embodiment of FIG. 68 and 69 are made in the form of a cylindrical structure of a functional carrier 937 placed inside the chamber 924, to which various additives, including useful agents such as drugs, biologically active materials and chemical elements and compounds, are connected, if possible, to further isolate . These additives are held by the carrier in such a way that when fluid flows through the chamber 924 and the fluid circulates around the carrier and through it, the additives are effectively released from the carrier and mixed with the liquid. It should be remembered that the adding means in chamber 924 may generally represent one or a combination of several of those previously described and shown in FIG. 66.

 When using the device of this latter form, first remove and remove the sterile caps 938 and 938a, which closed the ends of the bubble 922, as well as the sterile cap, which closes the open end of the cylindrical part 900. When the drug vial assembly is inserted into the open end 907f of part 900, the thread 923 will mesh with a thread 930a formed on the body 908. Clockwise rotation of the drug vial will cause the vial to move forward in the cylindrical portion 900, resulting in the cannula 927 flashing stomernuyu stopper 926. After the vial assembly with medicament finally snaps into place, ribbed cap 938a, which is used to rotate the vial, is removed and discarded.

 Once the drug vial is in place in the cylindrical portion 900, the open end of the fluid vial assembly 904 is inserted into the annular space 900a and the thread 916 formed on the cap or shell 915 is mated to the internal thread 918a adjacent to the neck of the cylindrical portion 900. As a result of the rotation of the assembly 904, the cannula 921 pierces the stopper 925 of the drug vial as shown in FIG. 69, opening a path for fluid to flow between the chamber 914 of the node of the vial with the diluent and the chamber 924 of the node chamber with the drug.

 Continued rotation of the bubble assembly with the diluent will cause the thread 916 to move into the free annular space 942, allowing force to push the bubble assembly to the right from the position shown in FIG. 68 to the position shown in FIG. 69. This movement will cause the elastomeric element 920 to move to the left in chamber 914, while pushing diluent D through cannula 921 and further into the drug vial assembly under significant pressure. The eluting diluent will pass through the glass disk 933 and then will begin to flow intensively around the support structure 937 of the adding agent. The diluent passing through the glass disk 934 and into the cannula 927 under pressure will cause the shut-off valve element 932 to move to the right, to the open position shown in FIG. 69, thus passing the mixture towards the reservoir 910 through the channel 909. The entry of this liquid mixture into the reservoir will cause the stretchable membrane 430 to stretch outwardly, as shown in FIG. 69. In such an extended position, the membrane 430 becomes an energy source for the controlled delivery of the liquid mixture from the device in the manner described above.

 After filling the reservoir, the diluent vial will move to the second section with thread 918b, continued rotation of the assembly will engage thread 912a on the shell with thread 918b and securely fasten the vial and assembly with the drug in the position inside the cylindrical part 900, which causes the patient to infuse the therapeutic substance.

 In FIG. 71-75 shows another embodiment of the invention. In this embodiment, the construction of the cylindrical part of the housing 950 and the base unit 951 is also similar to the construction of these components in the last considered embodiment of the invention and the same parts are denoted by the same positions. However, the last form of the invention is characterized in that while the fixed drug is contained in its own unit with a bubble 952, and the first part of the liquid component, or parenteral liquid, is contained in a separate unit 954, the reservoir is pre-filled with the second part of the liquid component.

 As before, the bubble assembly 954 may be combined with the bubble assembly 952 and with a cylindrical body for mixing the drug with the liquid component. With the special design used in this last form of the invention, the liquid already in the pre-filled reservoir can be mixed under control with the liquid in node 954 and with the additive in node 952 to obtain an infusible mixture which can then be released under the influence of an energy source or a stretchable membrane 430 provided by the invention. In other words, like devices corresponding to the previously described form of the invention, this embodiment allows controlled mixing of a portion of the first liquid component or carrier component located in ampoule 954 with the second component or additive contained in ampoule 954 to obtain a first mixture. This mixed carrier liquid mixture can then be introduced into a reservoir that was previously filled with a diluent or other liquid to form a second, suitable infusion fluid for subsequent infusion to the patient.

 As best seen in FIG. 71 and 75, in this last form of the invention, the cylindrical part 950 is connected integrally with the rear or concave surface 410 of the base element by means of connecting collars 410a. Part 950 also includes at its base a wall 956 with a socket 957, inside of which the nodes 952 and 954 are arranged in the manner best seen in FIG. 75. As best seen in FIG. 75, at the base 958 there is a channel 959, which communicates with the reservoir 960. The outlet of the device communicates with the reservoir 960 through the channel 872, the construction and placement of which are similar to those described previously.

 Similarly, the needle valve housing 874 of the type previously described in which the needle valve assembly 874a is housed extends outwardly from the rear surface 410 (see also Figs. 26 and 28). Valve 874a forms the second flow control means in the present invention for controlling fluid flow at the outlet of the device. It should also be noted that on the front surface of the base element there are also many intersecting microchannels 812 communicating with an opening 815 onto which the filter membrane 834 is adhered. The filtering means and microchannels 812 act in the same way to obtain the same result as previously described.

 Turning now to FIG. 73, the liquid bubble assembly 954 consists of a bubble 962 with a chamber 964 for receiving a liquid component, such as a diluent. The bubble 962 is tightly fitted with a two-piece plastic cap or sheath 965. The cap 965 is provided with an external thread 966 that mates with the connecting means shown here as an internal thread 968 made in the cylindrical part of the housing 950. A method for interconnecting a bubble with a liquid will be described below. and housing.

 The open end of the bubble 962 is closed by a sealed cap or stopper 970, in the center of which a cannula with a blunt tip 971 is tightly inserted, providing communication between the chamber 964 containing the liquid carrier component and the outer part of the bubble assembly. For purposes that will become apparent from what is said below, the plug 970 can move longitudinally in the chamber 964 from a first position near the open end of the bubble to a second position near the blind end. Prior to use, the open end of the bubble 962 and the cannula 971 are closed by a tear-off lid 972 of the standard type.

 Shown in FIG. 74, the drug vial assembly 972 includes a glass vial 974 with an internal thread 975 and a chamber 976. The chamber 976 is closed at one end by an elastomeric stopper 977a that is held in place by a crimped cap 778 that fits snugly against the vial 974. The opposite end of the chamber 976 with an internal thread also sealed with an elastomeric sealed stopper 977b, which the cannula 971 with a blunt end must be stitched, located centrally in the shut-off valve body 972 located in the chamber 973 located at the base 958. The cannula 971 provides the connection between the chamber 976 and the fluid channel 978 passing through the shut-off valve body and communicating with the reservoir 960 through the channel 959 with the shut-off valve 962 open. The following describes the operation of the shut-off valve 932 in the process of filling the tank 910.

 Next to the plugs 977a and 977b are distribution round disks made of porous glass 970 and 980, which are intended, as before, to properly regulate and distribute the liquid flowing through the chamber, in which there are adding means corresponding to the present invention and located between the distribution discs. Additives in the embodiment of FIG. 74 and 75, are made in the form of a cylindrical porous carrier 982, placed inside the chamber 976, with which various additives are connected, if possible, for further isolation, one or in combination. As in the previous embodiment, these additives are held by the carrier in such a way that when fluid flows through the chamber 976 and circulates around the carrier and through it, the additives are effectively separated from the carrier and mixed with the liquid. It should be remembered that the adding means in chamber 976 may generally represent one or a combination of several of those described previously and shown in FIG. 66 and 67.

 When using a device in accordance with this last form of the invention, the sterile caps 972 and 983b, with which the ends of the ampoules 962 and 974 are closed, and the sterile cap, which closes the open end of the cylindrical part 950, are first removed and removed. When the drug vial assembly is inserted into the open the end 957 of the part 950, the thread 975 engages with the thread 958, made next to the body of the shut-off valve 972. The clockwise rotation of the drug vial leads to the forward movement of the vial into the cylinder tion portion 950, whereby cannula 927 pierces the elastomeric stopper 977b.

 After the drug vial is in place in the cylindrical portion 950, the cap 983a is removed and the open end of the liquid vial assembly 954 is inserted into the annular space 958a. Then the thread 966, made on the lid or shell 965, mates with the internal thread 968, which is located near the neck of the cylindrical part 950. As a result of the rotation of the assembly 954, the cannula 971 pierces the drug vial plug 977a, opening the way for fluid to flow between the chamber 964 of the vial assembly with a liquid carrier and a chamber 974 of the drug chamber assembly.

 Continued rotation of the bubble assembly with the liquid carrier leads to its movement to the right, as shown in FIG. 75. This movement will cause the elastomeric element 970 to move to the left in chamber 964, pushing diluent D through cannula 971 into the drug vial assembly under significant pressure. The diluent will pass through the glass disk 979 and then will begin to intensively flow around the supporting structure 982 of the adding agent. An eluting diluent passing under pressure through the glass disc 980 and into the cannula 971 will cause the shut-off valve element 962 to shift to the right, to the open position shown in FIG. 75, thus passing the mixture towards the tank 960 through channel 959. This liquid mixture flowing towards the tank will be controllably mixed with the liquid component in the pre-filled tank to obtain a liquid mixture suitable for infusion. The elastomeric membrane 430 in the extended position becomes an energy source for the controlled delivery of the liquid mixture from the device by the method described above.

 Having now received a detailed description of the invention, made in accordance with the requirements for registration of patent applications, specialists in this field can easily make changes and modifications to individual details of specific nodes in order to bring them into line with specific requirements or conditions. Such changes and modifications may be made without departing from the spirit and scope of the invention set forth in the claims below.

Claims (37)

 1. A device for mixing the first and second components to obtain a fluid substance and for subsequent infusion of this substance, containing a container assembly comprising a container having walls forming an inner chamber for the first component, adding means located in the chamber for introducing the second component into the first component for mixing in the chamber, moreover, this adding means consists of adding the second component and means of adding additives to introduce the second component into the first component, moreover, the addition of additives includes a fluid channel and a valve assembly configured to be controlled by a control element, characterized in that an infusion device, a thin stretchable membrane, and a housing consisting of a base and a cover covering said base including a connecting means and device for infusion of liquid, while the connecting means is connected to the container and has a first channel for communication with the channel for the flow of liquid in the means for adding additives, W a second channel communicating with the first channel and including a shutoff valve connected to the control element with the possibility of movement between the first and second positions, and a third channel communicating with the second channel, the device for injecting liquid contains a base with an outlet in it and the first and second channels, and the first channel of the specified base communicates with the third channel of the connecting means, and the second channel of the specified base communicates with the first channel and the specified outlet thiium, and the stretchable membrane is made of elastic material and has the ability to overlap the base with the formation together with the base of the chamber for the second component, communicating with the first and second channels of the base and with the outlet, while the membrane has the ability to stretch when pressure is applied and has the ability to enter a chamber for pumping the second component into the container.  2. The device according to claim 1, characterized in that the container further comprises a sleeve with an internal thread and an external thread and a shell surrounding the container having an external thread interconnected with the internal thread on the sleeve.  3. The device according to claim 2, characterized in that the connecting means has an internal thread mating with the external thread of the sleeve.  4. The device according to claim 3, characterized in that the internal thread of the connecting means is configured to interact with the external thread of the sleeve, and the control element of the shut-off valve is configured to move the shut-off valve from the closed position to the open position.  5. The device according to p. 4, characterized in that when the shut-off valve is in the closed position, the shell has the ability to rotate relative to the sleeve with the shift of the control element in the open position for fluid to flow through the channels in the connecting means and the means of adding additives.  6. The device according to p. 5, characterized in that it includes filtering means for filtering the liquid in the means of adding additives, and the filtering means is superimposed on top of the membrane.  7. The device according to claim 5, characterized in that the infusion device further includes an outlet means for regulating the flow, communicating with the outlet and designed to regulate the flow of fluid through the outlet in the base.  8. A device for injecting fluid into a patient, comprising a container assembly including a container with a channel for flowing fluid and walls forming an inner chamber communicating with the channel for flowing fluid, adding means located in the chamber for adding additives to the fluid introduced into said inner chamber moreover, the adding means consists of the additive and the means of introducing additives intended for introducing the additive into the injected liquid, characterized in that a liquid infusion device is introduced therein, t a stretchable membrane and a housing consisting of a base and a cover covering said base, including connecting means and a device for injecting liquid, while the connecting means is connected to a container assembly and has a first channel for communication with a channel for fluid flow in the container, and a device for the liquid infusion contains a base with an outlet made therein and the first and second channels, the first channel communicating with the first channel of the connecting means, and the second channel communicating with an outlet, a thin stretchable membrane made of an elastic material and adapted to overlap the base with the formation of a chamber for containing liquid introduced into the container assembly, while the chamber communicates with the first and second channels in the base, and the membrane has the ability to stretch the liquid introduced into the chamber under pressure, and injection into the first and second channels in the base.  9. The device according to claim 8, characterized in that the means of adding additives consists of a structural base located in the specified container, and the additive contains a useful substance that is removed from the means of adding additives by affinity chromatography.  10. The device according to claim 8, characterized in that the additive is connected to the means of making additives with the possibility of subsequent removal using azlactone functional compounds.  11. The device according to claim 8, characterized in that said means of introducing additives consists of a structural base located in the tank, and biologically active proteins are associated with this structural base.  12. The device according to claim 8, characterized in that the container assembly includes a second flow control means for regulating the flow of fluid through the channel for fluid flow in this container.  13. The device according to p. 12, characterized in that the housing includes first means for regulating the flow of fluid passing through the fluid outlet at the base.  14. The device according to item 13, characterized in that the means for adding additives further includes a control means for controlling the first means of regulating the flow.  15. The device according to item 13, wherein the base includes an outlet in communication with the camera.  16. A mixing device comprising a container assembly, including a first container with a channel for fluid flow and walls forming an inner chamber communicating with the channel for fluid flow, adding means located in the chamber for introducing additives into the fluid introduced into the chamber, the adding agent consists of an additive and additive means for introducing this additive into a liquid, characterized in that a thin stretchable membrane and a metering device containing a housing are introduced into it, the outlet and the first and second parts, the first part comprising connecting means for connecting the container assembly to the first part of the housing, having a first channel for communicating with a channel for fluid flow in the first container, first flow control means for controlling the flow of liquid through the first dispensing channel devices, the second part contains a base with a hole for discharging liquid and a first and second channels for fluid flow therein, the first channel communicating with the first channel ohm of the connecting means, and the second channel communicates with the fluid outlet, the stretchable membrane is made of elastic material, has the ability to overlap the base with the formation of a chamber for containing liquid, communicating with the first and second channels of the base, while the membrane has the ability to stretch when the fluid is introduced into the chamber under pressure and forcing the liquid in the chamber into the first and second channels in the base after the return of the specified membrane to an unstretched connection.  17. The device according to clause 16, characterized in that the container assembly further comprises a second container with a chamber containing a liquid adapted to be connected to the first container.  18. The device according to 17, characterized in that the channel for the flow of fluid of the first tank includes an inlet and an outlet and in which the connecting means includes a cannula communicating with the first channel in the base, and in which the outlet of the channel for the flow of fluid of the first tank closed by the first sealing element punched by the cannula after connecting the container assembly to the first part of the housing.  19. The device according to p. 18, characterized in that the outlet of the channel for the flow of fluid of the first container is closed by a second sealing element and in which the second container includes a plug moving inside its chamber, including a cannula capable of punching the second sealing element of the first container, allowing leakage fluid between the chamber of the second tank and the channel for the passage of fluid of the first tank through the cannula.  20. The device according to p, characterized in that the chamber of the second container contains a diluent.  21. The device according to claim 20, characterized in that the additive contains a drug.  22. The device according to claim 20, characterized in that the additive contains a useful substance.  23. The device according to p. 22, characterized in that the adding means contains an additive that provides continuous release of the beneficial substance into the liquid for a certain time.  24. The device according to p. 22, characterized in that the means of making additives is made with the possibility of continuous release of additives for a certain time.  25. A mixing and delivery device comprising a container assembly including a container with a channel for flowing fluid and walls forming an inner chamber communicating with the channel for flowing fluid, adding means located in the chamber for introducing additives into the fluid introduced into said chamber through the channel for the flow of liquid, characterized in that it introduced a thin stretchable membrane and a delivery device consisting of a housing having first and second parts, the first part comprising a connecting means for connecting the container assembly to the first part of the housing, having a first channel for communicating with a channel for fluid flow in the container, and the second part contains a base with a hole for discharging liquid therein, first and second channels for fluid flow, the first channel communicating with the first channel of the connecting means, and the second channel communicates with the hole for the release of fluid, and a thin stretchable membrane is made of elastic material and has the ability to overlap the base with the formation of ka EASURES for containing said fluid administration, communication with the first and second base channels, wherein the membrane has the possibility of stretching the fluid introduced into the chamber under pressure for selectively inflating the first and second channels in the base.  26. The device according A.25, characterized in that the additive contains biologically active material.  27. The device according A.25, characterized in that the adding agent contains a polymer.  28. The device according A.25, characterized in that the means of introducing additives contains a carrier located in the tank and having the ability to transfer additives with the possibility of allocation.  29. The device according A.25, characterized in that the additive is essentially made with the possibility of removal from the means of adding additives by affinity chromatography.  30. The device according to clause 29, wherein the additive contains a base to which a ligand is attached, and a target molecule is connected to the ligand.  31. The device according to p. 30, characterized in that the ligand is attached to the base through the legs.  32. The device according to p, characterized in that the enzyme is attached to the target molecule.  33. The device according to p, characterized in that the target molecule is a protein.  34. The device according to p, characterized in that the antibody is connected to the protein.  35. The device according to p, characterized in that immunoglobulin is connected to the protein.  36. The device according to p, characterized in that the antibody is covalently linked to a protein, and the antibody has many communication sites facing outward from the protein.  37. The device according to clause 36, wherein the enzyme conjugate having the specificity of the target molecule is used as an antibody. Priorities for items:
04/17/92 according to claims 1 to 7;
03/19/93 according to claims 8 - 37.

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