FR2510413A1 - DEVICE FOR ADMINISTERING A PARENTERAL THERAPEUTIC AGENT - Google Patents

Abstract

THE INVENTION RELATES TO A DEVICE FOR ADMINISTERING A THERAPEUTIC AGENT PARENTALLY. THIS DEVICE IS CHARACTERIZED IN THAT IT INCLUDES: A. A PHARMACEUTICALLY ADMISSIBLE TANK OF LIQUID 11; B. A DROP BY DROP CHAMBER 18 COMMUNICATING WITH ITS RESERVOIR 11 TO DETERMINE THE FLOW OF LIQUID THROUGH THE PARENTAL ADMINISTRATION DEVICE 10; AND: C. A DOSING CHAMBER 22 WHICH COMMUNICATES WITH THE DROP CHAMBER 18 AND WHICH INCLUDES A WALL 24 SURROUNDING AN INTERIOR SPACE 25, AN INPUT 23 TO PASS THE LIQUID FROM THE SAID DROP CHAMBER 18 INTO THE SAID CHAMBER DOSAGE 22, AN OUTLET 26 TO ALLOW LIQUID TO LEAVE THE DOSING CHAMBER 22, AND A THERAPEUTIC AGENT CONTAINED IN THE said DOSING CHAMBER 22 TO FORM A DOSED SOLUTION OF THERAPEUTIC AGENT WITH THE LIQUID ADMITTED IN THE said DOSING CHAMBER 22. APPLICATION TO SIMULTANEOUS PARENTERAL ADMINISTRATION OF A PHYSIOLOGICAL LIQUID AND A MEDICINAL PRODUCT.

Description

The present invention relates both to a device

  This invention also relates to a method for administering a therapeutic agent parenterally using said parenteral administration device comprising the metering chamber, and a method for administering a parenteral therapeutic agent using said parenteral administration device comprising the metering chamber, and a method for add a therapeutic agent to

a physiological fluid.

  Parenteral administration of medicated liquids is common practice in medicine The fluids in question are administered especially intravenously, and this is a common practice that is widely used for the daily in medicine and surgery The most commonly used fluids are blood and its substitutes, dextrose solutions,

  of electrolytes and physiological serum chlorides

  these liquids are administered by means of a

  intravenous administration

  tank suspended above the patient, the liquid is

  lant through a hypodermic needle introduced into the

patient's body.

  The administration of intravenous fluids is a valuable and important practice that helps to improve the patient's condition optimally.

  There are no means or processes for administering

  concomitantly treat a therapeutic agent.

  Currently, such agents are administered intra-

  by one of the following methods: 10) The perfusion device is temporarily removed

  intravenously and stop the flow of physiological fluid

  the therapeutic agent is administered intra-

  venous, then reinsert the perfusion device into the

the vein of the patient.

  2) The therapeutic agent is added to the physiological fluid

  logic of the tank, so that it is brought to the patient

  by the flow of physiological fluid.

  ) The therapeutic agent is added to the physiological fluid

  logic in a separate tank that is connected to the line

  intravenous route through which the therapeutic agent

  tick is caused by the flow of physiological fluid

to the body of the patient.

  4) The therapeutic agent is contained in a vial into which a physiological liquid is introduced, and this vial is then connected to the primary line by which

  the drug is administered to the patient.

   ) The therapeutic agent is administered by means of a

  pump which exerts a certain pressure on a physi-

  logic containing the therapeutic agent for the purpose of

  intravenous administration of the liquid containing the agent.

  Although these techniques are used, they

  have major disadvantages. For example, the admi-

  administration of a drug by repeated insertion of a

  needle causes unnecessary suffering and trauma

  the; these techniques require separate connections

  for connection to the primary intravenous infusion line

  vein; the use of pumps can produce pressures that vary where administration takes place, and these pressures can lead to thrombosis; the speed of distribution of the drug to the patient is often unknown, since the speed of distribution of the drug is not controlled.

  the therapeutic agent which depends on the flow of the physio-

  logic; and these techniques often require a prior dosage of the drug by the hospital pharmacist or nurse. In view of the above, there is a

  imperative need in the field of

  especially in the field of intravenous administration, of a reliable device and method that can be used in hospitals for administering a parenteral therapeutic agent, and in particular

  intravenous, controlling the rate of administration.

  Accordingly, the main object of the present invention is to provide a delivery device by

  parenteral route that allows the administration of a therapeutic agent

  speed-controlled pimples to improve the care of people whose condition

  requires intravenous administration of a drug.

  Another object of the invention is to provide such a device comprising a dosing chamber which contains a therapeutic agent in order to introduce this agent into a parenteral liquid and to improve the care provided to patients.

  patients undergoing parenteral therapy.

  Another object of the invention is to provide a dosing chamber containing a measurable form of therapeutic agent, this chamber being suitable for use in a parenteral administration device for introducing the therapeutic agent at a speed. controlled

  thanks to its form allowing the dosage, in a liquid paren-

admitted in said room.

  Another object of the invention is to provide a parenteral delivery device comprising a dosing chamber of the therapeutic agent that contains a therapeutic agent and a membrane for controlling the speed.

  to dispense a dosed solution of the therapeutic agent

  tick at a speed controlled by the control membrane of

  the speed in the body of a receiver.

  Another object of the invention is to provide a parenteral administration device comprising a dosing chamber of the therapeutic agent which contains

  a form of this agent allowing the dosage, in order to

  to speed-control the therapeutic agent in a

  parenteral liquid allowed in said chamber.

  Another object of the invention is to provide a

  parenteral delivery device comprising a chamber

  dosage of the therapeutic agent which contains a

  the dispensing agent of this agent in order to admit the latter, at a speed controlled by the dispensing device, into a parenteral administration liquid to optimize the

  treatment of a patient under perfusion.

  Another object of the invention is to provide a therapeutic agent dosing chamber suitable for use with a parenteral delivery device, said chamber containing a therapeutic agent delivery device for admitting this agent at a controlled rate.

  essentially by this device, in a physiological fluid

logical admitted in this room.

  Another object of the invention is to provide a parenteral therapeutic system comprising a reservoir and a dosing chamber of the therapeutic agent which contains a device for releasing a drug, at a speed controlled by this device, in a physiological fluid which 'flows from the tank into the room' and from there to

a receiver.

  Another object of the invention is to provide a parenteral administration system comprising a primary route for the liquid and a secondary route for the liquid, the latter comprising a dosing chamber of the therapeutic agent which contains a) A a therapeutic agent delivery device for releasing a therapeutic agent into a physiological fluid that flows into the chamber, or: b) A therapeutic agent that in any case forms "in situ" a therapeutic agent solution which can

  to be administered to a human being or an animal.

  Another object of the invention is to provide a parenteral administration system comprising: 1) A primary route for the liquid comprising a dosing chamber which contains:

  a) a dispensing device releasing an agent -therapist-

  in a physiological fluid flowing into the chamber, or: b) a therapeutic agent; and

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  A secondary route for the liquid comprising a dosing chamber which contains:

  a) a dispensing device releasing a therapeutic agent

  in a physiological fluid that flows into the chamber, or: b) a therapeutic agent said therapeutic agent, in its form a) or b) producing "in situ" a therapeutic agent solution that can be

  administered to an animal or a human being.

  The invention relates to a parenteral administration system and a dosing chamber of a therapeutic agent suitable for use with this system. The dosing chamber contains: a) a therapeutic agent which can be dosed or mixed autonomously "in situ" with parenteral fluid

  entering the dosing chamber and then

  to a biological recipient, or: b) the assay chamber contains a therapeutic agent

  which is present from the outset in a distribution device

  of this agent or which is present in a form suitable for controlled rate dosing housed in the chamber, and which stores a certain quantity of therapeutic agent to carry out a prescribed program and distribute in a

  programmed in advance and without supervision a therapeutic agent

  tick in a liquid that enters the dosing chamber.

  The therapeutic agent, when it is dispensed by the dispensing means, is mixed in an amount dosed "in situ" with the physiological liquid that enters the metering chamber. In a preferred embodiment, the dispensing means release the therapeutic agent to a controlled rate which essentially is independent of the volume flow rate of parenteral liquid entering the dosing chamber to be subsequently administered to a recipient The invention also relates to a parenteral administration system for administering a solution dosage of therapeutic agent, wherein the therapeutic agent is mixed in a dosed amount with the liquid and wherein

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  the parenteral administration system comprises in combination

  naison: a) a reservoir containing a pharmaceutically acceptable liquid which is also a pharmaceutically acceptable carrier for the therapeutic agent; b) a metering chamber comprising a wall surrounding a free space and having an inlet surface that allows communication with the reservoir so that liquid can flow from the reservoir into the metering chamber and an exit surface through which the dosed solution of therapeutic agent leaves the chamber; c) a therapeutic agent, a dosage form of such agent or a dispensing device in the dosing chamber; and d) a conduit that communicates with the exit of the chamber and extends to the location of the recipient patient o

place the infusion.

  The invention also relates to a system of administration

  parenteral administration which comprises: 1) A primary route for the liquid comprising a reservoir of physiological fluid and a primary tube which

  communicates the reservoir and a common tube which

  duit to the place of perfusion; and: 2) A secondary route for the liquid comprising a

  mini-reservoir of physiological fluid that is in communica-

  tion with a dosing chamber of the therapeutic agent in turn communicating with a secondary tube and then with a common pathway for the liquid from which a

place the infusion.

  The invention also relates to an administration system

  parenteral administration comprising: 1) A primary route for the liquid comprising a saline reservoir, a drip chamber, a metering chamber and a primary tube which communicates with the metering chamber and a common tube leading to the place where the infusion takes place; and:) A secondary route for the liquid comprising a saline reservoir, a drip chamber, a therapeutic agent dosing chamber and a secondary tube which communicates with the dosing chamber and

  with the common tube that leads to the place of the infusion.

  The following description, which does not present

  no limiting character, will allow to understand

  how the present invention can be practiced.

  It should be read with reference to the accompanying drawings, of which FIGS. 1 to 7 show views in

  perspective or elevation of various forms of

  DESCRIPTION OF THE INVENTION FIGS. 8 to 25 show perspective or elevational views, sometimes partially cut away, of various embodiments of the dosing chambers that can be used in the infusion system.

Figures 1 to 7.

  FIG. 1 represents an intravenous infusion system according to the invention, and is designated in its

  together with the marker 10 The system 10 comprises a reservoir

  see 11 made of a flexible or semi-flexible plastic

  rigid, and preferably transparent, which may be polyvinyl chloride or a polyolefin, and it contains a physiological liquid suitable for intravenous administration. The physiological fluid 12 of the reservoir II may be, in particular, a sterile solution, such as an aqueous solution of dextrose, a solution of dextrose in a solution of chlorides, an electrolytic solution or a chlorinated serum The physiological fluid 12 is also an excipient for intravenous administration, and serves as a vehicle for a therapeutic agent that it is a question of administering to a recipient In the embodiment shown, the reservoir It is not in communication with the outside, the physiological liquid it contains is at atmospheric pressure, and the reservoir deflates when it empties the liquid 12 Generally, the tank 11 is able to be suspended, the collar downwards, to a hook 13 by a hole or a Anguette 14 which is attached to the tank 11 or which forms an integral part The tank it, at its end opposite to that by which it is suspended, so on his neck, has a delivery port 15 for receiving an infusion set . The infusion set provided by the present invention is for administering to a patient liquid 12 and a therapeutic agent that are introduced into the IV infusion system. The infusion set is sterile, non-combustible and disposable. The infusion set comprises the elements described below, and it is connected to the orifice 15 of the reservoir 11 The orifice 15 may be a not shown diaphragm of the reservoir 11, or this orifice 15 may be a hollow connector 16 This connector 16 is adapted to receive the end 17 of the chamber

  drip 18, this end 17 fitting closely

  The drip chamber 18 is used to trap the air and to allow the flow rate of the liquid 12 of the reservoir 11 to be adjusted when the flow is dripping. drop 18 is connected to a first section of a tube 20 which fits into the outlet 19 An adjustable clamp 21 of the wheel or screw type mounted on the tube 20 clamp

  the inside of the tube 20 to regulate the flow cooperatively

  The second section of the tube 20 is connected to the inlet 23 of the dosing chamber 22 of the therapeutic agent. A third section of the tube 20 is connected to the outlet 26 of the chamber. 22 and an adapter assembly and a needle 27, which is inserted into a vein and sometimes

  in an artery of a warm-blooded animal.

  The therapeutic agent dosing chamber 22 is a component according to the invention of the intravenous infusion system, whether the chamber alone or in combination with the system is considered. The dosing chamber 22 is dimensioned and adapted for its purpose. use in intravenous systems; it is complete in itself, it starts of itself, it realizes the dosage of

251041 3

  autonomous, it does not require an external energy source

  The dosing chamber 22 contains a therapeutic agent that can be administered intravenously, and the use of the dosing chamber containing the therapeutic agent

  requires no reconstitution of a mixture before use.

  The metering chamber 22 is a lightweight disposable chamber that includes a wall 24 surrounding and defining an interior space or enclosure. The chamber 22 has an inlet 23 that is designed and dimensioned so that

  place the chamber 22 in an intravenous infusion system.

  venous, and it has an exit 26 which is also

  designed so that the chamber can be placed in the system.

  The inlet 23 and the outlet 26 are made to receive the tube 20. The chamber 22 is made of glass, plastic or a similar material and, as shown, it is made of a transparent material allowing

  see its structure and the therapeutic agent it contains.

  The therapeutic agent of the chamber 22 may be in any form known in the pharmacy that allows a therapeutic substance to be obtained by mixing with the liquid entering the chamber. Examples of pharmaceutically acceptable forms are the solids, crystals, micro-crystals, particles, pellets, granules,

  powders, tablets, spray-dried products

  or the tablets which undergo disintegration and dissolution in the presence of a parenteral and, especially, intravenous administration liquid, such as compressed particles, compressed powders, compressed granules and friable therapeutic agent, in a delivery device which, with a flow rate controlled by the dispostif, delivers the therapeutic agent to the fluid entering the dosing chamber

  22, according to a given formula, or in a similar device.

  In general, the metering chamber 22 stores a certain amount of therapeutic agent in a dispensing device, in a form allowing the assay, or in a pharmaceutically acceptable form or in a

  similar form, in order to carry out a therapeutic program

  In other words, it is a quantity of therapeutic agent making it possible to provide, in a programmed manner in advance and without supervision, a quantity of this therapeutic agent.

  medically active to produce a therapeutic result

  beneficial tick In general, the dosing chamber 22

  has a capacity of about 10 milliliters to

  liters of liquid or more, and it may contain from about milligrams to 20 grams or more of therapeutic agent in various pharmaceutically acceptable forms and in

various dispensing devices.

  The term "therapeutic agent", such as

  hereinafter, means any substance which produces a therapeutic or beneficial effect, such as a drug, carbohydrate and / or like product. The term "fluid" or "liquid" means a fluid or liquid that may be

  administered parenterally, including intravenously

  venous, and it includes pharmaceutically liquid

  which are also pharmaceutical vehicles

  These are acceptable for therapeutic agents, such as water, isotonic sera, Ringer's lactate, and the like. The term "assay," or "dosage of the therapeutic agent," as used herein, generally indicates that the therapeutic agent is dosed, mixed, added, dissolved, suspended, transported, and / or subjected to a similar treatment in or by the liquid in a physico-chemical form acceptable for its parenteral injection , including intravenous In a further embodiment of the invention, the metering chamber 22 may operate simultaneously as a drip chamber while housing a device or agent.

25104 1 3

  In this embodiment, the dosing and drip chamber is used to obtain

  drip of the liquid at a specific rate

  For example, the dosing and drip chamber may have a high rate of drops for adults and a slower flow rate for pediatric uses. The dosing and drip chamber can be made with various size inputs. different to act on the flow rate of the drops, or one can act on the flow by means of an adjusting clamp mounted on the tube which brings there the liquid The metering chamber and drip can provide, for example, from 2 to 75 drops per milliliter on a peridian lasting from one minute to one hour Preferably, the therapist can adjust the flow rate from 1 to 20 drops per minute, or depending on the

  Patient's needs An additional description concerning

  the dosing chamber 22 will be presented in the following

of the present description.

  FIG. 2 represents another system of perfu-

  according to the invention which is designated as a whole by the reference 10 The system 10 is suspended on a support 30 in its operating position The system 10 is the

  orifice type which requires air for its operation.

  The system 10 comprises a reservoir 31 made of glass or

  in a rigid and transparent plastic material suitable-

  sealed with a rubber stopper not shown

  The reservoir 31 contains a liquid 33 which is preferably capable of parenteral administration. The air enters the system 10 through an inlet. air 34 which is formed as a part of the inlet closure 35 of the drip chamber 36 A hollow tip 37 pierces the rubber closure of the reservoir 31 and serves as a conduit for allowing the air to pass from the air inlet 34 into the tank 31, and also to allow the liquid 33 to pass from the tank 31 into the drip chamber 36 In the figure, we see an end 38 of the tip 37 in the tank 31; the other end of the tip 37, not shown, enters the drip chamber 36 to bring the liquid 33 from the tank 31 to the drip chamber 36 The drip chamber 36 is hollow, tubular and of a conventional type, and it consists of a wall surrounding an internal cavity which receives the liquid; it is connected to a metering chamber 39 through a first tube section 40 inserted into the outlet end 41 of the drip chamber 36, and also inserted into the end 42 of the metering chamber which is clean to receive the tube 40 The other end 43 of the metering chamber 39 is adapted to receive a second tube section 44 The metering chamber 39 is made of glass or plastic, and is preferably transparent The metering chamber 39 may have any form suitable for use in a parenteral delivery system, including intravenous, and is preferably round, its length being greater than its width. The ends 42 and 43 are closely fitted to the wall of the chamber 39 to form a closure

  airtight and leak-free and house a dispensing system

  sateur which releases a therapeutic agent in order to produce in situ a solution of this agent in the chamber 39 with

  the liquid 33 which enters the chamber 39 from the reservoir

  see 31, and this, by mixing or dissolving A tube 44 brings the solution containing the therapeutic agent from the

  room 39 up to a needle 45 which allows its administration

  A regulating clamp 46 is mounted on the tube 40 to clamp the inside of this tube 40 and therefore

  adjust the flow of liquid through the system 10.

  FIG. 3 represents another system 10 according to

  the invention for infusions, usually intravenously

  The system 10 comprises, in combination, a reservoir 48, a container containing a pharmaceutically suitable liquid, and includes an internal communication tube 49 which allows air to enter the reservoir when the liquid medicament is infused into the reservoir. Patient The reservoir 48 is closed by a plug not shown, and it has a hole for the air passage tube k 9 The reservoir 18 is connected by a hollow tip adapter and closed 50 to the infusion system to bring a liquid drug

  from tank 48 to the patient through the system 10.

  The tip 50 is connected to a first tube section 51 which penetrates into a drip chamber 52. This drip chamber 52, as previously described, is preferably made of a transparent material such as glass or glass. plastic material, which makes it possible to count by sight a measurable number of drops which pass through said chamber per unit of time A second section of tube connects the drip chamber 52 to a metering chamber 53 The second section of tube 51 It passes through a clamp 54 which is used to regulate the flow. The metering chamber 53 comprises a wall 55 which surrounds an internal space 56 In the space 56, this chamber 55 contains a metered quantity of a therapeutic agent 57 represented points that allows for a therapeutic program, or it can

  housing a dispensing device or other form of medical

  Agent 57 is in a pharmaceutical form.

  It is acceptable that it can be dissolved, or it can disintegrate into smaller fragments and dissolve in the presence of liquid in the chamber 55 to form a drug solution. Alternatively, the chamber 55 may contain a filter element that provides

  a sterile liquid by removing the liquid from the particles

  and / or bacteria, this element does not interfere

25104 13

  i 4 with the flow of the liquid which passes through the chamber It is possible to act on the product supplied by such a system by means of

  for example, the rate of dissolution that is determined

  the particle size of the therapeutic agent

  and the solubility of this agent in the liquid, by means of the discharge rate by a dispensing device, or by any other similar means The chamber 55 has an end 58 for receiving the inlet tube 51 and the physiological fluid of the reservoir 48, and it has another end 59 for receiving the outlet tube 51 The tube 51 brings the solution of the chamber 53 which contains an active amount of therapeutic agent 57, through a needle 60, to a patient in order to produce the desired beneficial effect.

  FIG. 4 represents an infusion system according to the invention which is designated as a whole by reference numeral 10. The system 10 comprises a primary reservoir 62

  which is made of a flexible or semi-flexible plastic

  rigid, preferably transparent, such as a non-toxic polyolefin, polyvinyl chloride or a

  The primary reservoir 62 is a reservoir

  of high capacity and contains a physiological fluid

  63 which is suitable for

  parenteral, intravenous or other physiological fluid

  63 of the reservoir 62 may be, in particular, a sterile solution, such as an aqueous solution of dextrose, electrolytes or a serum of chlorides. In the embodiment shown, the reservoir 62 is not in communication with the outside, the physiological fluid is at atmospheric pressure, and the reservoir deflates when it empties the physiological fluid 63 Generally, the reservoir 62 is able to be suspended, the collar downwards, at a hook 64 by a hole or a tongue 65 who

  is attached to the reservoir 62 or in the form of an integral part.

  This tank, at its opposite end to that by which

25104 1 3

  it is suspended, therefore on its neck, has an administration port intended to receive a primary pathway for

the liquid.

  The primary route is used to provide physiological saline 63 to the patient via the parenteral delivery system. The primary route is sterile, incombustible, and disposable. The primary route includes the items to be described hereinafter, and is connected to the primary route. at the orifice 66 of the reservoir 62 The orifice 66 may be a diaphragm not shown of the reservoir 62, or this orifice 66 may be an adapter adapted to receive a hollow connector 67 The connector 67 may receive the end 68 of the chamber drip 69 This is

  used to trap air and it also allows, in co-

  operation with an adjusting clamp 70, to adjust the flow of physiological fluid 63 from the reservoir 62 when the flow takes place drop by drop An outlet 71 of the drip chamber 69 is connected to one end of a primary tube 72 that passes through a forceps

  setting 70 which clamps its internal section to adjust the flow of

  The other end of the primary tube 72 is connected to a valve 73, downstream of which a common tube 74 connects the valve 73 to a needle adapter assembly 75. which is introduced, for example, into a vein

of a warm-blooded animal.

  In addition, the system 10 includes a sec-

  for the liquid, which consists of a secondary reservoir 76 or "mini-bag" which is made of a material

  flexible or semi-rigid plastic, preferably

  As a nontoxic polyolefin, polyvinyl chloride or the like, the secondary reservoir 76 is a parenteral reservoir of low capacity and contains physiological saline 78 which is suitable for the

  parenteral, intravenous or other treatments.

25104 13

  Physiological fluid is a pharmaceutical vehicle for parenteral administration, i.e. a vehicle for a drug to be administered to a patient In the embodiment shown, reservoir 76 is not in communication with the outside, the physiological liquid 78 is at atmospheric pressure and the reservoir deflates when it empties the physiological fluid 78 The reservoir 76 is able to be suspended, the neck downwards, at a hook 64 through a hole or a tab 79 which is fixed to the reservoir 76 or which forms an integral part The reservoir 76, at its end opposite to that by which it is suspended, so on its neck, comprises a delivery port for receiving

  a secondary route for the liquid.

  The secondary route according to the invention is used to administer to a patient the physiological saline 78 to which a medicament has been added. The secondary route is

  sterile, incombustible and disposable

  takes the elements described below, and is connected to

the orifice 80 of the reservoir 76.

  The orifice 80 may be a diaphragm (not shown) mounted in the reservoir 76, or this orifice 80 may

  be an adapter for receiving a hollow connection 81.

  The connector 81 receives the end 82 of a drip chamber 83. The latter is used to trap the air and, in cooperation with an adjusting clamp 84, it also makes it possible to regulate the flow of physiological fluid 78 coming out of the reservoir 76 when the flow takes place drop by drop An outlet 85 of the drip chamber 83 is connected to one end of a section of a secondary tube 86 passing through an adjusting clamp 84 which clamps its internal section to regulate the flow in cooperation with

  the drip chamber 83 whose interior is visible.

  The other end of the secondary tube 86 is connected to a chamber 87 for the determination of the therapeutic agent. The adjustment clamp 84 is used to act on the flow of the

  fluid in a dosing chamber 87 of the therapeutic agent

  The metering chamber 87 is made of glass or

  plastic material, and is preferably transparent.

  The metering chamber 87 may have any form suitable for its use in a therapeutic system.

  parenteral administration, and is preferably

  round, its length being greater than its width.

  The end of the secondary tube 86 fits snugly on the end cap 89 of the chamber 87. The end of the secondary tube can be fitted into the cap 89 or it can slide on the receiving tube - an element of the cap 89 for provide an airtight and leak-free enclosure intended to contain at least one therapeutic agent, or a dispensing device Optionally, the chamber 87 is provided with a membrane to act on the dispensing speed, this membrane not shown being able to be a micropore membrane or a similar member which acts on the rate of delivery of the therapeutic agent solution exiting the chamber 87 Such a membrane may rest on a sintered glass support which is an integral part of the chamber, or it may be sealed by an adhesive on the inner wall of the chamber 87, or fused to this wall, or supported by the wall of the chamber by pinching inwards, or resting on a collar in the chamber, or supported by the end cap 90 positioned in the chamber 87, or suitably attached to this cap. A secondary tube section 91 brings the therapeutic agent in solution from the chamber 87 to the valve 73. Adjusting clip 92 is mounted, if necessary, on the tube 91 to assist in controlling the flow of therapeutic agent solution from the dosing chamber. The adjusting clip 84 may be used alone, in cooperation with the clip 70, and all

  two in cooperation with the valve 73, to act on the flow

  In a preferred embodiment, the valve 73 is a three-position valve. Therapeutic agent solution is supplied from the valve 73 to the patient. through a common tube 74, to the needle assembly 75 which is intended for parenteral administration to a recipient. This means that the liquid can be taken from the primary route, the secondary route or both routes. placing the valve in the

  desired position to allow flow to the recipient.

  For example, the liquid may pass through the tube 72, the valve 73, the tube 74 and the needle 75, or by the tube 91, the valve 73, the tube 7 'and the needle 75, or even the valve can be adjusted to bring liquid

from both ways.

  FIG. 5 shows a parenteral delivery system according to the invention which is generally designated by the reference 10. The system 10 of FIG. 5 is an air-passage type system which requires air for its operation. system 10 includes a glass reservoir 94 which is suitably sealed by a

  rubber stopper which contains a physiological liquid

  The reservoir 94, in its operating position, is suspended from a support 95 and the air enters this reservoir 94 via an air filter 96 connected to the reservoir 94. by a point 97 which is hollow and which pierces the rubber closure 94 of the reservoir The other end of the tip 97, not shown, enters a drip chamber 98 and it passes the physiological liquid of the reservoir 94 in the drip chamber 98 The latter is connected to a primary route for the liquid 99 which is constituted by a tube for use

  medical device bringing physiological fluid to the needle 100.

  A roller clamping valve 191 is mounted on the liquid pathway 99 to reduce the cross-section of the primary path 99 and to regulate the flow of the liquid through the primary path 99. The system 10 of FIG.

25104 13

  also comprises a secondary channel 102 for the liquid, which joins a common channel 103 to a branch 104 This can be made in the form of a Y-shaped connecting tube which receives the tube 99 of the primary channel, the tube 102 of the secondary way and the tube 103

* common way.

  The secondary path includes a reservoir 105 which is a mini-tank or a mini-glass bottle which

  is properly sealed with a rubber stopper

  not shown, and which contains a physiological liquid

  suitable for parenteral administration, including

  intravenous In its operating position, the

  see 105 is suspended from the support 95, and the air enters the reservoir 105 through a filter 106 connected to the reservoir 105 by a tip 107 which is hollow and pierces the rubber closure of the reservoir 105 The other end of the tip 107, not shown, enters a room

  from drop by drop 108 and she passes the physio- liquid

  The latter is connected to a secondary channel 102 for the liquid, which is constituted by a tube for medical use, bringing to the needle 100 the physiological liquid which carries a therapeutic agent. roller clamp 109 is mounted on the secondary channel 102 for the liquid to reduce the cross section of the secondary path 102 and to regulate the flow of the liquid through the secondary path to the dosing chamber 110 of the therapeutic agent The latter is dimensioned and adapted for use in the system of administration by

  Parenteral route The metering chamber of the therapeutic agent

  peutique 110 is complete in itself, it begins with

  It also does not require an external source of energy and can be manufactured at low cost. The metering chamber 110 is lightweight, disposable and includes a wall 111 that surrounds and defines a space or light. The metering chamber 110 has an inlet 113 which receives the secondary channel 102 and an outlet 114 which also makes it possible to place the chamber 110 in the secondary path 102. The chamber 110 is made of glass, plastic or a material analogous and, as has been shown, it is made of a transparent material that allows to see its structure The chamber 110 can house a therapeutic agent or a device dispensing such an agent A dissolved solute formed in the chamber 110 leaves this last by the secondary route 102, he joins the physiological fluid of the lane 99 in the junction 104 and passes in the lane

  103 to be administered to a recipient.

  Figure 6 illustrates another system of administration

  parenteral administration 10 according to the invention The system 10.

  comprises a primary path 118 and a secondary path 119 belonging to a therapeutic agent delivery device which is suspended over a patient by a loop support 120. The primary path 118 comprises, in combination, a reservoir 121 which is a pharmaceutically acceptable physiological saline reservoir 122, and has an internal air supply tube 123 which allows air to enter the reservoir 121 when the physiological fluid leaves the reservoir 121 and is administered to a patient The reservoir 121 contains a large volume of a sterile liquid which serves to modify and maintain the physiological functions of the receiver. The reservoir 121 is

  closed by a plug 124 held in place by a pleated edge

  An air passage tube 123 extends through the plug 124 to allow the admission of air into the reservoir 121. The latter is in communication, with respect to the liquids, with a drip chamber 126 by its pointed hollow end 127 which pierces the plug 124 As has been described above, the drip chamber 126 is used for counting with the naked eye

104 13

  the number of drops 128 of physiological fluid that passes through said drip chamber 126 per unit of time The drip chamber 126 comprises a sealed space retaining physiological fluid and is closed at its ends by two caps 129 and 130 which are tightened on the tubular wall 131 to form said sterile fluid chamber This chamber is made of a material

  transparent like glass or a transparent plastic

  The physiological fluid 122 leaves the drip chamber 126 through a first section of tube 132 which brings the physiological liquid to the metering chamber 133. The latter comprises a wall 134 which surrounds a catheter. internal space and it is closed at its ends 136 and 137 by closure members which fit on said wall of the chamber The tube 132 enters the closure member 136 to establish a communication for the liquid between the dosing chamber and the drip chamber, and a second tube 138 which passes through a flow control clamp 139 brings it liquid to a two-way valve 140 Through the valve 140, the liquid passes into a common tube 141 and a needle set 142 to be

administered to a recipient.

  The secondary path 119 includes a reservoir 143

  which is a means for storing a pharmaceutical liquid

  The reservoir 143 has an internal air supply tube 145 which allows air to enter the reservoir 143. The latter is closed by a plug 146 held in place by a ring 147. mini-tank or a mini-bottle and it contains about 100 to 500 milliliters of a liquid that is used to continuously convey a drug or to convey it discontinuously to a patient The reservoir 143 is connected to a drop chamber 148 through a hollow tip adapter 149 to deliver physiological fluid to a patient from the reservoir 143 and through the secondary pathway The drip chamber 148 is designed so that it can be counted. number of drops 150 which pass through said drip chamber over time The physiological fluid leaves the drip chamber through a first

  section of tube 151 which leads to a metering chamber 152.

  This therapeutic agent dosing chamber 152 comprises, as described above, a wall formed of a liquid impermeable material which surrounds an internal space for accommodating a unit dosage amount of a therapeutic agent, or a dispensing device The chamber 152 has a known volume and, preferably, it comprises a volumetric scale which indicates the volume of liquid contained in said chamber The chamber 152 has an end 153 designed to receive the inlet tube 151 and another end 154 configured to receive the outlet tube 155 The tube 155 passes through a clamp 156 which may be used as an opening and closing member or as a flow regulator to act on the flow of the liquid through the Secondary route The tube 155 brings the liquid carrying the therapeutic agent of the chamber 153 to the valve 140 and thence through the common communication tube 1 41, to a needle assembly 142 and

to a receiver.

  With regard to its operation, the parenteral delivery system of FIG. 6 is used as the parenteral delivery system of FIG. 5 This means that the system of FIG. 6 can be used:) To administer a pre-selected physiological fluid containing a therapeutic agent selected in advance by opening the adjusting clip 139, closing the adjusting clip 156 and placing the valve 140 so as to allow liquid to flow out of the tube 138 in the tube 141;

25104 13

  ) To administer a different physiological fluid

  selected in advance by opening the adjusting clip 156, closing the adjusting clip 139 and placing the valve 140 so as to allow the liquid to flow out of the tube 155 in the tube 141, and: 3) To administer for a given dosage period a given volume of liquid containing a known amount of therapeutic agent as follows: a) The liquid is allowed to flow through the primary route or the secondary way by putting the valve 140 in

  closed position for the primary or secondary track

  (b) A known volume of liquid is allowed to enter one of the dosing chambers, this volume being determined by

  reading of the meniscus position on the volumetric scale

  that is present on the wall of the room,

  c) The therapeutic agent is dosed in the dissolving chamber.

  a given amount of therapeutic agent present in the chamber or provided by a device contained in the chamber, in the known volume of physiological fluid which corresponds to the solubility of the therapeutic agent in the physiological fluid as a function of time, and d) The recipient is provided with a metered quantity of solution, when desired, by putting the valve 140 in the desired position so that the solution flows from the desired dosing chamber. liquid or different drugs, or different liquids and different drugs, by selecting in advance the liquid and the drug for

  the primary and secondary ways.

  drug administration on a continuous basis,

  alternated or with interruptions.

  Fig. 7 shows another system 10 of administration

  Parenteral administration according to the invention The system 10

25104 1 3

  is a gravity flow system for the administration of

  two physiological liquids and two therapeutic agents in independent flow or in cooperation through two distinct distribution channels, namely a primary route and a secondary route. The primary route 158 comprises a reservoir 159 which contains a primary physiological liquid 160 which must to be administered to a patient for an extended period of time, and he is

  suspended in operating position to a support 161.

  The primary fluid dispenser reservoir 159 is made of glass or a transparent, non-toxic plastic material and is sterile sealed. The reservoir 159 is sealed by means of a rubber stopper 162 which is held in the reservoir 159

  by a closure 163 with annular retaining ring.

  The primary reservoir 159 is in communication, with respect to the liquids, with a drip chamber 164 which is in communication with the reservoir 159 by means of a hollow piercing tip 165 which passes through the stopper 162 in the reservoir The drip chamber 164 is a conventional air supply type chamber which is well known in medical practice. Essentially, the drip chamber 164 is made in two parts, namely a conical housing. 166 who receives the liquid and a cap 167 to his

  entrance, and it ends with an exit port 168.

  The drip chamber 164 allows air to enter the parenteral delivery system through an air inlet 161 'which forms an integral part of the hooded inlet 167 Droplet flow 169 of the liquid from the reservoir 159 is adjusted by a clamp 170 mounted downstream on the primary track A first section of medical tube 171 inserted in the outlet 168 establishes the communication of the liquid between the drop chamber to

  drop 164 and the inlet 175 of the metering chamber 172.

25104 1 3

  The metering chamber 172 is dimensioned and designed so that it can be used in the parenteral administration system. This therapeutic agent dosing chamber 172 is complete in itself, it starts on its own, it does not require an external source of energy and can be manufactured at low cost The metering chamber is of low weight, it is disposable and, in a preferred embodiment, it is made of a clear and transparent material As the glass or the plastic material The metering chamber 172 comprises a wall 173 which surrounds and forms an internal space 174,

  and it has a closure 175 at its entrance to receive

  see the tube 171 and a closure 176 at its outlet which is adapted to receive a tube 177 The tube 177 passes through a clamp 170 which is intended to restrict the internal section of the tube 177 to adjust or stop the flow of liquid through The primary route The tube 177 enters a coupling member 178 in the form of a Y-shaped connecting tube which receives the tube 177 of the primary channel and a common tube 179 which leads to an injection member 180 to administer the dosed agent solution

therapeutic to a recipient.

  The secondary path 181 comprises a reservoir 182 which is a mini-reservoir or mini-bottle made of glass or plastic which is suitably sealed by means of a rubber stopper 183 held in the reservoir 182 by a closure ring 184 in its position. In operation, the reservoir 182 is suspended from a support 161 and contains a physiological liquid 185 which is equally suitable for parenteral administration, including

  intravenously, as a vehicle for a therapeutic agent

  The air enters the reservoir 182 through an air inlet 186 which forms an integral part of a tip 187, which is hollow and pierces the rubber plug of the reservoir 182. The other end 188 of the tip 187 passes through the inlet closure 189 of the drip chamber 190 to pass drops 191 of saline from the reservoir into the drop chamber at

  drop The drip chamber 190 is in communica-

  This chamber 193 for dosing the therapeutic agent is produced in the same manner as the metering chamber 172 described in FIG.

  the primary route, and this description applies

  The metering chamber 193 is connected to a secondary tube 194 which is made of a material for medical use and which passes through a V-clamp 195 to adjust or stop the flow of the therapeutic agent in solution. through the secondary path The tube 194 enters the connection 178 to allow flow into the common way 179 and into the body of a patient through

a needle assembly 180.

  The therapeutic agent found in the assay chambers 172 and 193 may be in any pharmaceutical form, and may be present as such or in a device which assumes an assay from a therapeutic agent. and a physiological fluid entering the chambers 172 and 193 and from a physiological fluid that enters these

  chambers 172 and 193, which does not require any

  Introduction or addition prior to use The flow of physiological fluid into the metering chamber 172 or 193 can be started, stopped, adjusted or interrupted by the forceps or pliers 195, or both, which allow the tube 177 or 194 to remain open or closed and which partially obstruct the passage of the liquid through the tube 177 or 194, and the flow of the therapeutic agent solution can be adjusted in the same way from

rooms 172 and 193.

  During its operation, the system 10 of administration

  parenteral administration may be used by a doctor,

251041 3

  a nurse or practitioner in a hospital, as follows:

  ) To administer a saline fluid containing

  a therapeutic agent through the primary path by adjusting the adjusting clip 170 in the opening direction and closing the adjusting clip 195 to prevent the flow of liquid into the secondary path, thereby through the primary route and in the hypodermic needle 180;

  20) To administer a saline fluid containing

  a therapeutic agent through the secondary path by adjusting the adjusting pliers 195 in the opening direction and closing the adjusting pliers 170 to prevent the flow of liquid in the primary path, thereby through the secondary route and in the hypodermic needle 180; and:) To administer a certain quantity of therapeutic agent contained in a known volume of liquid from the two channels by regulating the flow of the liquid through the adjusting tongs 170 and 195, the liquid of the two channels mixing into one Common liquid at connection 178 for subsequent administration to a patient The operations provided by these embodiments of the invention make possible the continuous or interrupted delivery of two different therapeutic agents contained in two different physiological fluids across two different routes, as well as the administration of two different therapeutic agents in different physiological fluids during the same interval of time of administration of the therapeutic agents.

  Figures 8 to 25 describe forms of reali-

  the structure of the dosing chambers which can

  to be used in the intravenous administration system of Figures 1-7.

  FIG. 8 shows a disposable lightweight weighing chamber 197 suitable for use in patients whose condition requires the parenteral administration of a physiological liquid containing a therapeutic agent. In FIG. the chamber 197 comprises a body 198 which is in the form of a tube, and is provided with a pair of caps 199 and 200 to form a closed chamber for containing the physiological fluid and the therapeutic agent. The caps 199 and 200 are fitted on the body 198 and, preferably, they are made of a self-sealing rubber through which it is possible to insert a needle or a hollow point, or rubber provided with a hole previously drilled and covered with A latex disc is in communication with the interior of the chamber 197. The metering chamber 197 is preferably hermetically closed.

  sealed, moisture-proof, micro-impervious

  organisms and permeable to ionizing radiation for

  that it is possible to sterilize it.

  FIG. 9 shows a metering chamber 201, part of which has been removed so that the inside of the hollow body of this chamber can be seen. In FIG. 9, the chamber 201 comprises a wall 202, part of which has been removed and ends 203 and 204 The closure ends 203 and 204 fit over the body of the metering chamber 201, these ends 203 and 204 being provided with an organism Y (cptptir C 205 and 206 which receives a The slide chamber 201 contains a therapeutic agent 207 which is soluble in a physiological fluid, such as an intravenously administrable liquid, and a film 208 made of a liquid which can be administered intravenously. material to act on

  the flow of the physiological fluid and the therapeutic agent

  The film, in an advantageous embodiment, is made of a polymer

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  acting on the speed of distribution of the therapeutic agent

  such as a micropore polymer such as a poly-

  carbonate, a semi-permeable polymer such as cellulose acetate, or a diffusion polymer such as a copolymer of ethylene and vinyl acetate The polymer film according to this embodiment of the invention is used in a preferred embodiment to control the speed of

  distribution of the solution containing the therapeutic agent

  from the chamber 201, i.e. the release of the therapeutic agent and the flow of the liquid through the chamber 201. The latter is shown with a film at its exit, but, if desired, it is could

  have a film at the entrance.

  Fig. 10 shows an exploded dosing chamber 209 which comprises the particulate therapeutic agent 210, a polymer film 211 for acting on the dispensing rate, which may be of cellulose acetate or the like, and a filter 212. The latter is a filter of conventional type whose pore size is between 0.1 and 5 microns, and preferably equal to 0.22 or 0.45 micron, and which is intended to eliminate the solution in flow the bacteria and unwanted material, in order to maintain the

sterile nature of the solution.

  FIG. 11 represents a dosing chamber 213 which comprises a body 214 provided with a wall and presenting

  the shape of a tube and which is provided with a pair of

  2 and 215 to form a closed chamber containing the liquid and a dispensing system The caps 215 and 216 are fitted to the chamber 213 and each has a tubular extension 217 and 218 which form an integral part thereof and which are intended to receive a The hollow tubular members 217 and 218 preferably have a tubular section so that they can receive a tube which slides into or onto the corresponding member. The dispensing system shown in the metering chamber 213 houses a multiplicity of small calibrated pills 219 for the controlled release of a therapeutic agent, including a drug, into a liquid entering the chamber 213 The small pills are shown in detail on the pill 220 which is shown in section, and

1,221

  comprise a drug core / surrounded by an envelope 222 made of a product to control the release rate The small calibrated pills 219 have a high surface area, which allows to obtain high dissolution rates during the formation of the solution The total number of small pills 219 in the metering chamber 213 may be variable, providing additional means for controlling the amount of therapeutic agent made available to form a solution of this agent. 222 can be selected from the materials that release the drug 221 according to various physico-chemical mechanisms. These mechanisms include erosion, diffusion and osmosis. When the envelope 222 releases the drug by osmosis, it also releases it by splitting. In one embodiment, the drug 221 is present as an osmotic solution. ee, such as a therapeutically acceptable salt, and has an osmotic pressure gradient across the shell 222 with respect to an external liquid. The materials that are used to form the shell 2 are those which are permeable to the passage of an external liquid and substantially impermeable to the passage of medicament The usable material may be selected from the group which comprises cellulose acylate, cellulose diacylate, cellulose triacylate, acetate Cellulose, Cellulose Triacetate, and Analogous Products The osmotic casing can be made to coat the drug in various thicknesses by coating to the turntable granulator, by coating to the spray turntable, by Wurster coating by means of a suspension of liquid in air, or by any similar process The shell is formed using organic solvents such as methylene chloride, methanol, methylene chloride, acetone, methanol and acetone mixtures , ethylene dichloride and acetone, and the like solvents The materials used to form an osmotic envelope, the processes to form such an envelope and the processes of osmotic burst are described in

  U.S. Patent Nos. 2,799,241, 3,952,741, 4,014,334 and 4,016,880.

  In another embodiment, the envelope 222 of the small pills 213 may be made of a material to control the rate of drug release. This means that the drug 221

  dissolved in the envelope or through pores of the enve-

  loppe and passes through the envelope or pores of this

  last at a rate controlled by diffusion in time.

  Useful materials for forming a diffusion envelope

  or an envelope provided with pores are for example a copoly-

  mother of ethylene and vinyl acetate, ethyl cellulose, polyethylene, crosslinked polyvinyl pyrrolidone, a copolymer of vinylidene chloride and acrylonitrile,

  polypropylene, silicone, and the like.

  The envelope can be applied using the techniques that have been described above, and the materials usable for forming the envelope 222 are described in US Patents

  Nos. 3,938,515, 3,948,262 and 4,014,335.

  The envelope 222 of the small pills 213 may be made of a bioerodible material that erodes at a controlled rate and releases the drug 221 to the liquid of the chamber 213. Such bioerodible materials

  that can be used to form the envelope 222

  Polycarboxylic acid, polyesters, polyamides, polyimides, polylactic acid, polyglycolic acid, polyorthoesters and polycarbonates. These polymers and processes for forming the shell 222 are described in US Pat. 811 k 444, 3,867,519, 3,888,975, 3,971,367, 3,993,057 and 4,138,344. The amount of drug present in a small sized pill is generally in the range of about 10 to 20 milligrams, and the number of small pills in a The small pills comprising an envelope and an inner drug core have a diameter of at least 100 microns, and in a preferred embodiment, their size is from 10 to 1000, and preferably from 50 to 150. diameter is

  at least 2,000 microns Small pills may

  One or more thicknesses of the product constituting the envelope As an option, the chamber 213 is provided with a support 223 for the small pills. This support 223 may be a film having release rate control properties and it may be realized. into a polymer that releases the drug from the chamber 213, this

  support 223 may be a membrane of micro-polymer

  porous, a sintered glass support, a perforated grid

and / or a similar organ.

  Fig. 12 shows a similar metering chamber 224 comprising a wall 226 surrounding a space 227 having an inlet 228 and an outlet 229. The chamber 224 contains a plurality of small capsules 230, one of which, 231, has been shown in cross section. capsule 230 includes a

  wall 232 surrounding a volume of liquid medicine 233.

  These small capsules can be manufactured by a

  that consists, essentially, to form three immiscible phases together, namely a liquid phase of manufacture, a phase of the product constituting the core and a phase constituting the coating The latter is deposited in liquid form on the material of the core and

  made solid, generally, by thermal techniques,

  by cross-linking techniques or by desolvation techniques to form microcapsules Capsules made using this technique exhibit

251041 3

  However, particle size is not critical for the implementation of the invention. The preparation of microcapsules is described in: Biochem Z, vol. 232, pages 338 to 345, 1931 (Bungenberg de Jong and Kass), Colloid Science, Vol 11, "Reversible systems", published by HR Kruyt, 1949, Elsevier Publishing Co, Inc. New York, J Pharm Sci, vol 59, No. 10, pages 1,367-1,376, 1970, and Pharmaceutical Science,

  Remington, vol. XIV, pp. 1,676 to 1,677, 1970, Mack Publish

  shing Co, Easton, PA Dosing chamber 224 contains

  also a film 234 which supports the small caps

  and which can furthermore serve as a means of regulating the distribution of the drug solution from the

dosing chamber 224.

  FIG. 13 shows a metering chamber 236 which comprises a wall 237 surrounding an interior space 238

  and which has an inlet end 239 and an end

  The chamber 236 contains a multiplicity of hollow fibers 241, one of which, shown in partial section in the figure, comprises a wall 242 which may be made of a semi-permeable polymer, a polymer permitting diffusion, a micropore polymer, a rolled product,

  or a laminated product with two or more

  244 which contains a medicament 244 The hollow fibers have a large exposed surface, which

  allows to release a large quantity of therapeutic agent

  The hollow fibers may be from a few millimeters to several centimeters or more, a diameter of one millimeter or more, and the chamber contains a hollow fiber with several hundred fibers or more. Hollow fibers have apertures 241a and 241b at each end, and can be produced from non-cellulosic polymers using spinning techniques in the state

  fades that use correspondingly shaped dies.

  These hollow fibers can also be manufactured by

  spinning a cellulosic solution in an organic solvent

  in certain regeneration products, namely n-octanol when the solvent is dialkylacylamide and n-hexanol when the solvent is dimethylsulfoxide. The hollow fibers can be filled with medicament using a drug solution which is injected into one open ends of the fiber, by immersion

  in a drug solution, or by a similar method.

  The hollow fibers can release the drug by diffusion

  by dialysis, osmosis, dissolution or

  In addition, the amount of therapeutic agent

  The amount of fiber free fiber can be adjusted by choosing the size and number of hollow fibers that are contained in the metering chamber. A method for making hollow fibers is described in US Pat. No. 4,086,418. 236 contains

  a support 245 for retaining the fibers, this support allows

  both the passage of the liquid containing a metered quantity of

  medication from room 236.

  FIG. 14 shows a metering chamber 246, seen in partial section, which comprises a wall 247 which surrounds a space 248 and which is provided with an inlet 249 and an outlet 250 for introducing and discharging the liquid into and out of the chamber 246 contains a multiplicity of fibers 251 containing a drug 252 which is represented by dots. The fibers 251 which form the dispensing system of the drug may be of natural or synthetic origin and may have a wide variety of structures (solid, semi-solid, porous, and others), and various geometric shapes (round, oval,

  square, trefoil) and various lengths and sections.

  These fibers can function effectively as

25104 13

  drug reservoir, the latter being dispersed through the fibers Suitable fibers can be manufactured by conventional methods For example, the material of

  fibers and the drug can be dissolved in soil.

  extruded through the small holes of a die and then solidified by conventional hot, dry, or wet spinning techniques. In another embodiment, the fibers can be made by pumping

  a mixture of fibers and medicine through a die.

  Thanks to such a process, the diameter of the fibers can vary from a few tenths of a micron to a millimeter

  the processes of stretching upwards or downwards.

  The interior of the chamber may contain fibers of various diameters. The fibers which form the drug reservoir may be filled, saturated or partially filled with drug by immersion, by infiltration or by a process of this kind which allows the fibers to be transferred to the fibers. desired amount of drug Other methods and drugs for forming the fibers are described in US Patent Nos. 3,228,887 and 3,921,636. The constituent materials of the fibers may be polyolefins, polyamides, polyurethanes, cellulosic products and products. Fiber processes are described in "Encyclopedia of Science and Technology", Vol. 5, pp. 263-276, 1971, edited by McGraw Hill Co., New York. Chamber 246 also contains a membrane 253 which supports fibers and which may be constituted by a porous or diffusion polymer cooperating with the fibers to adjust the amount of soil ution of

  drug that is administered to the patient.

  Fig. 15 shows a metering chamber 255 having a portion of the wall 256 removed to show its interior space 257 which receives a delivery system 258 for the therapeutic agent. The system 258 comprises a reservoir formed of a polymer which can be eroded, and a 259 part of this system was removed to show

25104 1 3

  the agent 260 dispersed therein. The polymer can be

  eroded is selected from the group that includes polyortho-

  esters, polyorthocarbonates, polyglycolic acid, polyacetic acid, polyacetals, polyketals, polyamino acids, and the like. The corresponding processes and erosion polymers are described.

  in US Patent No. 4,180,646, in Int J of Pharmaceutical

  Vol. 7, pp. 1-18, 1980, and Biodegradable and delivery systems for contraception, Chapter 2, edited by ESE Hafex and WAA Van Os, and published by GK Hall, Boston, 1980. may also comprise a film of polymer 261 cellulose acetate or a similar product that allows

  to set the release speed, as well as a filter 262.

  The filter 262 is of a conventional type and its pores 263 have a size of 0.1 microns to 5 microns, and preferably 0.22 or 0.45 microns, to remove from the flowing solution. bacteria and unwanted material and help preserve sterility

of the solution.

  Figure 16 shows a dosing chamber 265

  which contains a therapeutic agent release system

  comprising a plurality of ion exchange resin particles 266 to which a therapeutic agent 267 is ionically attracted Resins may be present

  in the form of particles, grains or droplets.

  The particles may have a variable size which is generally between 10 and 350 mesh. The resins may be homopolymers, copolymers, their derivatives, or cross-linked resins. These resins include

  ion exchange resins such as styrene divinyl-

  The active agent 267 is released from the resin 266 into the liquid which enters the metering chamber to form in this chamber.

  a therapeutic agent solution to be administered to a patient.

  The chamber 265 may also contain a film 268 to adjust the release rate and a filter 269 which has pores 270 to prevent bacteria and other unwanted material from leaving the assay chamber. These are described in United States Patent No. 420,444. Fig. 17 shows a metering chamber which contains a dispensing device. The metering chamber may be used in a primary tract, a secondary tract, or in both lanes, which means that the assay chamber shown can be used in either or both of the routes. The therapeutic agent assay chamber 272, as seen in FIG. 17 is another component according to the invention of the parenteral administration system In the embodiment shown, the dosing chamber comprises a wall 273 which surrounds and defines an internal space The chamber 272 has an inlet 275 which is designed and dimensioned to mount the chamber 272 in an intravenous delivery system, and it also has an outlet 276 which is also designed and sized to mount the in the system The inlet 275 and the outlet 276 are made to receive an incoming or outgoing tube The chamber 272 is made of glass, plastic, or a similar product, and, as has been shown, it is made of a transparent material that allows to see its structure

  and a device contained therein In the form of reali-

  2, chamber 272 comprises two housing halves 277 and 278 which fit one over the other and which contain the

  the therapeutic agent 279 within the space 274.

  Retaining means 280 in the housing 278 allow the passage of the liquid, hold the device 279 in the space 274 and prevent the device 279 from blocking

251041 3

Exit 276.

  The dispensing device 279 shown in FIG. 17 is in the form of an osmotic device for controlled rate release of a solid of the kind disclosed in US Pat. No. 3,845,770 to Felix Theeuwes and Takeru Higuchi. osmotic device 279 seen by transparency comprises a semi-permeable wall 281 in

  cellulose acylate, of cellulose diacylate,

  cellulose acetate, cellulose acetate, cellulose diacetate, cellulose triacetate, or a

  similar, this wall surrounding and defining a compartment

  282 containing a therapeutic agent 283 or a medi-

  The dosage agent 283 has an osmotic pressure gradient across the wall 281 of the device 229 relative to the liquid contained in the chamber 272. The therapeutic agent assay device may comprise an agent that has a osmotic pressure gradient, or it may comprise an agent mixed with an osmosis-active product, such as sodium chloride, potassium chloride, and the like, which has a significantly higher osmotic pressure gradient to that of the liquid contained in the chamber 272 A passage 284 extends through the semi-permeable wall 281, and it communicates

  with the compartment 282 and the exterior of the device 279.

  In operation, the liquid enters the chamber 272 and is soaked through the semipermeable wall 281 of the device 279 into the compartment 282 with a tendency toward osmotic equilibrium at a rate that is determined by the permeability of the wall and the osmotic pressure gradient across the wall, which produces a solution containing the therapeutic agent 283 in the compartment 282 which is released through the passage 284 at a speed controlled by the device 279 for an extended period of time. therapeutic agent in solution of the device 279 that mixes

104 1 3

  homogeneous with the liquid of the chamber 272 is controlled, in this embodiment, by the device 279, and, essentially, it is independent of the flow of the liquid through the chamber 272 The device 279 retains its physical and chemical integrity throughout the process

of liberation.

  Fig. 18 shows a metering chamber of the therapeutic agent 272 in open view, and this chamber contains another device 285 for releasing a therapeutic agent into an intravenously administrable liquid which enters the chamber 272. is shown open, and it comprises an inner mass transfer conductor 286 shown as a solid core and formed of a polymer such as hardened polydimethylisoxane, through which the therapeutic agent is dispersed 286 Around the mass transfer conductor 286 there is a membrane 288 which controls the release rate of the therapeutic agent and which is

  preferably formed of a polymer such as polyethylene.

  Conductor 286 and membrane 288 are both permeate

  287 by diffusion, which means that the therapeutic agent can dissolve in and diffuse through the conductor 286 and the membrane

  288 However, the permeability of the conductor 286 is greater than

  than that of the membrane 288, and the latter therefore acts as a means of action on the release rate of the therapeutic agent of the device 285.

  maintain its integrity throughout the period of

  This therapeutic agent dispensing device 285 is described in FIG.

U.S. Patent No. 3,845,480.

  FIG. 19 shows the dosing chamber of the therapeutic agent from which part of the wall has been removed and this chamber contains a dispensing device 289 for releasing a therapeutic agent at a speed controlled by the device 289 into a liquid which

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4 o

  enters the chamber 272 The device 289 is represented

  it is open and comprises a reservoir 290 constituted by a mass transfer liquid conductor 291 such as a liquid therapeutic oil carrier which is permeable to the passage of the therapeutic agent and which contains the therapeutic agent 292, which may be phenobarbital The

  tank 290 is surrounded by a wall 293 which is

  killed by a substance which makes it possible to control the rate of release of the therapeutic agent or of the drug, which is permeable to the passage of the therapeutic agent 292 and which may be a polyolefin The rate of passage of the therapeutic agent 292 through the wall 293 is smaller than its rate of passage through the conductor 291, so that the release of the therapeutic agent by the

  wall 293 is the step of controlling the release speed

  agent when it comes to releasing him from the

  289 The latter retains its physical and chemical integrity throughout the agent's release process.

  Therapeutic device for releasing the therapeutic agent

  peutique -'89 is described in the US patent

No. 3,993,073.

  Figure 20 represents another form of reali-

  In a second embodiment of the assay chamber 272, a portion of the wall has been removed and contains another device 294 for delivering a therapeutic agent into a liquid entering the chamber 272 to form a metered solution of a therapeutic agent which can be used intravenously. device 294 is seen in section and it includes a wall 295

  surrounding a reservoir that contains the therapeutic agent 297.

  This reservoir consists of a permeable solid support

  the passage of the therapeutic agent which may be poly-

  dimethylsiloxane containing "diazepam" as a medicament.

  The wall 295 is made of a microporous material whose pores contain a substance which makes it possible to act on the release rate of the therapeutic agent and which is

25104 1 3

4 i

  permeable to the passage of the therapeutic agent 297, this material

  riau can be a microporous polymer obtained by co-

  precipitation of a polycation and a polyanion

  The therapeutic agent 297 is controlled by the device 294 which retains its physical and chemical integrity throughout the process in which it is in the chamber 272. The device 294 is described in US Patent No. 3,993 072.

FIG. 21 shows a metering chamber 272, part of the wall of which has been removed and which contains

  a device 298 for providing a therapeutic agent

  tick to a physiological fluid entering the chamber

  272 to form "in situ" a metered solution of therapeutic agent.

  may be administered intravenously.

  The device 298 comprises a matrix 299 which contains a therapeutic agent 300 distributed through this device.

  Matrix 299 is made of a poly-

  merized which is not subject to erosion, which means that it retains its physical and chemical integrity over time, and is permeable to the passage of the therapeutic agent 300 by diffusion The release rate

  of the therapeutic agent from the matrix is determined

  undermined by the rate at which the therapeutic agent

  dissolves in the matrix and passes through it through

  so that it is here the control phase of the release rate of the therapeutic agent from the matrix The latter can have any shape that can fit into the chamber 272, like the shape of a rod, disc or other similar

  polymers discussed here include poly-

  olefins such as polyethylene containing muscle relaxants or similar substances Materials that can be used to make these devices are

  described in U.S. Patent No. 3,921,636.

  FIG. 22 represents, in open view, a metering chamber 272 which contains a device 301

25104 1 3

  The device 301 is shown in an open view and is made of a micropore polymerized material 302 through which a therapeutic agent 303 is dispensed. The matrix 302 is constituted by an inert and non-toxic polymer that is not

  not subject to erosion and which includes a plurality of micro-

  pores to release the therapeutic agent at a speed

  controlled in the liquid that enters the chamber 272.

  Microporous materials that can be used in the present application are described in US patents

Nos. 3,797,494 and 3,948,254 -

  Fig. 23 shows a therapeutic agent dosing chamber 272 which is shown open and which contains a device 304 for supplying a therapeutic agent to a saline fluid entering the chamber 272. The device 304, shown open, comprises deposits A therapeutic agent 305 is dispersed in a polymer 306 which substantially surrounds them individually and is impermeable to the passage of the therapeutic agent and permeable to the passage of the liquid entering the chamber 272. osmotic pressure gradient across the polymer relative to the liquid entering the chamber 272 The therapeutic agent 305 is released at a controlled rate by the liquid from the chamber through the polymer, which dissolves the deposits and generates a hydrostatic pressure in the chamber. these deposits, this pressure being applied to the wall of the deposits forming which release the therapeutic agent at a controlled rate of time The polymer 306 is not subject to erosion, and the device 304 may be in the form of a matrix, a stem, a disk or In other analogous forms The methods and materials which can be used to manufacture dispensing devices operating by osmotic burst are described in US Pat.

No. 4,177,256.

  FIG. 24 represents an open view of a chamber

  of the therapeutic agent 272 which contains a

  The device 307 is shown open, and comprises an outer wall 308 which is made of a liquid-permeable semi-permeable polymer substantially impervious to therapeutic agents. and solutes A layer 309 of an osmosis-effect solute which is for example sodium chloride is deposited on the inner surface of the wall 308 A solute layer 309 surrounds an inner reservoir 310 which is made of a material

  flexible impervious to solute and therapeutic agent.

  The reservoir 310 comprises a passage 311 which makes it possible to dispense a therapeutic agent 312 into a liquid contained in the chamber 272. The device 307 dispenses the therapeutic agent because the liquid diffuses from the chamber 272 through the outer wall 308 and dissolves continuously. the solute 309 tending to the osmotic equilibrium, which continuously increases the volume between the wall 308 and the reservoir 310 This increase in volume causes the reservoir 310 to deflate continuously and provides the therapeutic agent 312 of the device 307 to the liquid which passes through the chamber 272, at a controlled rate and through the passageway 311 Osmosis-based therapeutic agent dispensing devices are described in US patents

Nos. 3,760,984 and 3,995,631.

  FIG. 25 represents a dosing chamber provided with an internal bag 315 intended to contain a therapeutic agent 316 which is for example a drug such as ephedrine sulfate. The bag 315 consists of a

  wall 317 which is made of a material of the kind of poly-

  diffusion, semi-permeable or microporous mothers allowing the passage of the physiological fluid in the pocket 315 and the passage of the therapeutic agent solution formed in this pocket out of the latter in a form of

  realization, and when the wall 317 is made of a poly-

  semipermeable mother, this wall may be provided with a dispensing orifice for providing the therapeutic agent solution to the chamber 314 The wall 317 is joined to the wall 318 of the chamber 314 by an adhesive, by sealing to The wall 318 is made of a material substantially impervious to the passage of the therapeutic agent, the physiological fluid and the therapeutic agent solution which is formed inside this wall. device, the liquid enters the chamber 314 and then into the pocket 315 where it forms a solution containing the therapeutic agent which passes into the chamber 314 and which, from there, is then administered to a recipient The device of FIG. to regulate the flow of the liquid regardless of the therapeutic agent distribution This distribution is governed by the mass transfer characteristics of the membrane 317, and the flow liquid is governed by a resistant element which is for example a regulator

  flow mounted on the path of the liquid.

  This parenteral delivery device can be used to deliver a large number of therapeutic agents, particularly when it is desirable to administer by infusion such agents, especially intravenously, intraarterially, intraperitoneally or subcutaneously. In an embodiment, for example, in the case of intraperitoneal administration of a saline fluid and a drug, the parenteral delivery device is connected to a cannula that passes through the abdominal wall of the patient. a form of

  preferred embodiment, this device for administering paren-

  is used for intravenous administration.

  In such therapy, the parenteral delivery device can be used to replace substances intravenously, for example to administer

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  plasma, a chlorinated serum, or a similar product, and to administer simultaneously or intermittently a therapeutically effective amount of drug In another embodiment, it is a question of restoring the electrolyte balance, for example by providing sodium ions, potassium or chloride or other analogues, a drug being administered simultaneously to a patient who needs a restoration of electrolyte balance and administration of an injectable drug intravenously This device can be used also

  for intravenous nutrition, for example by administering

  dextrose, with concomitant or periodic administration of a drug that can be injected

  intravenous to a patient who justifies such treatment.

  In addition, the device according to the invention of administration

  parenteral route comprising a primary route, a secondary route

  and a dosing chamber of a therapeutic agent in one or both pathways, can be used as an intravenous therapeutic device in practice.

veterinary art.

Claims (10)

CLAIMS -   Apparatus for administering a therapeutic agent parenterally, characterized by comprising: a) a pharmaceutically acceptable liquid reservoir (11; 31; 48; 62,76; 94,105; 121,143; 159,182); ; b) A drip chamber (18; 36; 52; 69,83;   98, 108; 126, 148; 164, 190) communicating with said reservation   see to determine the flow of liquid through the   parenteral administration; and: c) a metering chamber (22; 39; 53; 87; 110; 133,152; 172,193) which communicates with the drop chamber at   drop and which includes a wall surrounding a space   an inlet for passing the liquid from said chamber drip into said dosing chamber, an outlet for allowing liquid to leave said dosing chamber, and a therapeutic agent contained in said chamber;   to form a dosed solution of therapeutic agent   with the liquid admitted into said dosing chamber.   2 Device according to claim 1, characterized in that it comprises: -   a) a pharmaceutically acceptable liquid reservoir (62, 76; 94, 105); b) a drip chamber (69, 83; 98, 108) communicating with said reservoir; and c) a common channel (74; 103) communicating with said drip chamber to receive liquid from said drip chamber and communicating with said metering chamber to receive a metered solution   therapeutic agent from said dosing chamber.   3 Device according to claim 1, characterized in that it comprises: a) a pharmaceutically acceptable liquid reservoir (121, 143; 159, 182); b) a drip chamber (126, 148; 164, 190) communicating with said reservoir; c) a metering chamber (133, 152; 172, 193) communicating with said drip chamber and including a wall; surrounding an interior space, an inlet for passing liquid from said drop chamber to   in said dosing chamber, an outlet for allowing   liquid to leave said dosing chamber, and a therapeutic agent contained in said dosing chamber to form a dosed solution of therapeutic agent with the liquid admitted into said dosing chamber; and d) a common path (141; 179) communicating with said metering chambers for receiving dosed therapeutic agent solutions from said metering chambers. 4 Device according to claim 1, characterized in that the therapeutic agent of the dosing chamber is   present in a dispensing device of this agent.   Device according to claim 1, characterized in that the therapeutic agent of the dosing chamber is present in dosable form.   Device according to claim 1, characterized   in that the therapeutic agent is a medicine.   7 Device according to claim 1, characterized in that a membrane is present in the dosing chamber to help control the release rate of the agent   therapeutic of the dosing chamber.   8 Device according to claim 1, characterized in that it comprises a tube for flowing liquid of the dosing chamber.   Device according to claim 3, characterized in that the therapeutic agent of the dosing chamber is a drug.   Device according to claim 3, characterized in that the therapeutic agent of the dosing chamber is   present in a dispensing device of this agent. 25104 1 3   11 i Device according to claim 3, characterized in that the therapeutic agent in the dosing chamber   is present in a dosable form.   12 Device according to claim 3, characterized in that a membrane is present in the dosing chamber to help control the release velocity of the agent   therapeutic of the dosing chamber.