FR2791574A1 - METHOD AND DEVICE FOR STERILIZING AND DISPENSING A LIQUID FOR MEDICAL USE - Google Patents

Abstract

A device for preparing a sterile liquid comprises means for validating a sterilization treatment applied to the liquid comprising calculation means for calculating a parameter representative of the sterilizing value (F0) of the sterilization treatment from the value of at least minus an operating parameter of the device (Q, Tin, THin, All, THout), and comparison means for comparing the calculated value of the parameter representative of the sterilizing value (F0) with a first threshold value F0min1 corresponding to sterility some cash.

Description

METHOD AND DEVICE FOR STERILIZING AND DISPENSING A LIQUID

FOR MEDICAL USE

  The present invention relates to a method and a device for sterilizing and dispensing a liquid for medical use. There are many surgical or medical treatments which require the use of large quantities of sterile liquid, in particular of liquid suitable for being injected into a body cavity or into the vascular circuit. As an example, we can mention hemofiltration, which is one of the treatments used to compensate for kidney failure. Hemofiltration consists in extracting from the blood of a patient, by ultrafiltration, a determined quantity of plasma water and simultaneously perfusing in the patient a lesser quantity of a so-called substitution solution, which is sterile and contains the main electrolytes of the blood. in respective concentrations

  identical or close to that of the blood of a healthy patient.

  For a four-hour hemofiltration session, it is not uncommon to prescribe an exchange volume for which approximately sixteen to twenty liters of substitution solution must be available. Another example of treatment that requires the use of a large amount of sterile fluid is automatic peritoneal dialysis. The principle of peritoneal dialysis, which also aims to compensate for renal failure, is to infuse into the peritoneal cavity of a patient a determined amount of a sterile solution containing an osmotic agent such as glucose and the main electrolytes of blood in respective concentrations close to those of the blood of a healthy patient. The solution thus perfused is allowed to stagnate in contact with the peritoneum, which behaves like a natural dialysis membrane, for the time necessary for the solution to enrich the impurities of the blood (urea, creatinine) in an optimal manner. The used solution added with the plasma water which the glucose made migrate in the peritoneal cavity is then drained out of the belly of the patient, then it is

  replaced with fresh solution.

  In the classic peritoneal dialysis mode, called "continuous ambulatory peritoneal dialysis (CAPD)", it is the patient himself who performs the drainage and filling operations of his peritoneal cavity, by connecting a collection pocket or a pocket filled with solution at the end of a

  catheter permanently installed through its abdominal wall.

  The liquid is transferred from the peritoneal cavity to the collection pocket and from the solution pocket to the peritoneal cavity by gravity, the collection pocket being kept below the level of the abdomen and the pocket filled with solution. being kept cool above the level of the abdomen. Typically, a patient performs the drainage-filling operations which have just been described four to five times during the day and the exchange

  relates to two liters of liquid each time.

  In the peritoneal dialysis mode called "dialysis

  automatic peritoneal (APD) ", drainage operations-

  filling are carried out at night, during the patient's rest, using a machine essentially comprising a pump for circulating the spent liquid and the fresh dialysis solution, a heating device for heating the fresh solution, a balance for weigh the pockets of fresh solution and used liquid and measure the weight loss, and a programmable control unit for controlling

  alternating stagnation and drainage cycles-

  filling. As this mode of treatment is administered by a machine and during the patient's rest, it makes it possible to increase the number of exchanges compared to conventional peritoneal dialysis: one usually proceeds from five to ten exchanges per night, which requires have ten to

thirty liters of fresh solution.

  In general, the sterile liquids used for the implementation of medical treatments of the type of those which have just been mentioned are industrially prepared and are

  packaged in flexible plastic bags.

  In addition to being unsuitable for the production of unstable solutions (sodium bicarbonate), this method of preparation has several drawbacks, in particular the cost of transporting and storing pockets of heavy and bulky solutions and the need to manage products. having expiration dates. To remedy these drawbacks, devices have been proposed for preparing liquids

  sterile medical devices at the place of their use.

  The document EP 0 622 087 describes a process for the on-line preparation of a sterile and pyrogen-free liquid which is obtained by filtration of a dialysis liquid produced by a

classic dialysis.

  The document GB 2 034 584 describes a process for the preparation of a sterile liquid, the sterility of which is obtained by heating the liquid to a determined sterilization temperature for a determined time. A device for implementing this method, which is designed to fill bags with the sterile liquid, comprises: - heating means for raising the temperature of a liquid immediately upstream of a sterilization unit constituted by a portion insulated circuit; - a circuit connected to the sterilization unit, having a first end connected to a source of liquid to be sterilized and a second end connected to a connector having a first outlet for delivering sterile liquid; - an evacuation pipe connected to a second outlet of the connector, and - pumping means for circulating the liquid

in the main circuit.

  This device further comprises means for degassing by heating the liquid to be sterilized upstream of the heating means and the sterilization unit in order to prevent the liquid from carrying bubbles during the sterilization treatment. Although this document presents prior degassing as a satisfactory solution to the problem posed by the presence of bubbles in a liquid subjected to a sterilization treatment, it is doubtful that, without other precautions, a liquid brought to high temperature will not carry bubbles

  simply because it was previously degassed.

  Furthermore, this document eludes two questions to which, according to the invention, it is necessary to provide an answer when undertaking to sterilize a liquid. The first question relates to what is meant by "sterilization" and the second question relates to the microbiological quality of

  device that is used to perform sterilization.

  It should be remembered that sterility defines a microbiological quality of the so-called "sterile" object and that according to standard EN 556 as well as according to the American Pharmacopoeia and the European Pharmacopoeia, for a device or a liquid to be labeled sterile, it that the theoretical probability of the presence of a viable microorganism in this

  device or this liquid is less than or equal to 10-6.

  However, the control of this level of presence 10-6 by an examination of the finished product is doubly impossible, both because the sampling necessary for this control according to Poisson's law of probability is impracticable, both because, in practical terms, the manipulations necessary to control samples give rise to a probability of contamination such that, even if the sampling were feasible, the

  test results would be wrong.

  An object of the invention is to provide a sterilization process and a device for implementing this process which make it possible to guarantee the sterility of the liquid prepared by

the device according to the method.

  To achieve this goal, a device for preparing a sterile liquid is provided, in accordance with the invention comprising: - adjustable main heating means for raising the temperature of a liquid inside a heating enclosure, - a main circuit comprising: * a first pipe having one end connectable to a source of liquid to be sterilized and another end connected to an inlet of the heating enclosure, and * a second pipe having an end connected to an outlet of the heating enclosure and another end connected to a connector having a first outlet for delivering a sterile liquid, - first pumping means for circulating the liquid in the main circuit, - means for validating a sterilization treatment applied to the liquid comprising calculation means for calculating a parameter representative of the sterilizing value (F0) of the treatment at p from the value of at least one operating parameter of the device (Q. Tin, THin, Tout, THout), and comparison means for comparing the calculated value of the parameter representative of the sterilizing value (F0) with a first threshold value FOminl

  corresponding to the sterility of the liquid.

  For example, the calculation means are provided for calculating the parameter representative of the sterilizing value (F0) of the treatment applied to the liquid from a mathematical model of the distribution of the temperatures in the heating enclosure, of the temperature (Tin , All) of the liquid entering or leaving the heating chamber, the temperature of the heating liquid (THin) and the flow rate of the liquid (Q) in the heating chamber. According to a characteristic of the invention, the device further comprises control means for controlling the pumping means and / or the heating means so that the calculated value of the parameter representative of the sterilization value (FO) is greater than the first value of

FOminl threshold.

  According to another characteristic of the invention, the device further comprises means for preventing the formation of bubbles in the liquid during sterilization of the liquid, such as an adjustable opening valve disposed on the second pipe of the main circuit and controlled for set the liquid pressure to a pressure value higher than the vaporization pressure of the liquid, what

  whatever the temperature of the liquid.

  According to yet another characteristic of the invention, the device further comprises means for sterilizing the second pipe and the connector for delivering the sterile liquid comprising: - means for validating a sterilization treatment applied to the second pipe and to the connector, and - means for preventing the formation of bubbles in the liquid during the sterilization of the second pipe

and connector.

  The subject of the invention is also a method for sterilizing and dispensing a liquid comprising: - heating the liquid in a heating chamber to a temperature and for a time suitable for sterilizing the liquid; validate the sterilization treatment applied to the liquid by calculating a parameter representative of the sterilizing value (F0) of the treatment from the value of at least one operating parameter of the device (Q, Tin, THin, All, THout), and by comparing the calculated value of the parameter representative of the sterilizing value (F0) with a first threshold value FOminl corresponding to sterility

some cash.

  Other characteristics and advantages of the invention

  will appear on reading the description which follows. We are

  refer to the accompanying drawings in which: Figure 1 shows the diagram of a first embodiment of a device according to the invention; FIG. 2 represents the diagram of a second embodiment of a device according to the invention; Figure 3 is a perspective view of a first embodiment of a heat exchanger according to the invention; Figure 4 is a perspective view of a second mode

  for producing a heat exchanger according to the invention.

  The device for preparing and dispensing a sterile liquid shown in FIG. 1 essentially comprises main heating means 80 having a heating enclosure 511 for the liquid, and a main circuit having a first pipe 1 connected to an inlet of the enclosure. heating 511 and a second line 2

  connected to an output of the heating enclosure 511.

  The main heating means 80 include a

  tank 81 for a heating liquid (oil or ethylene-

  glycol, for example) connected by a pipe 83 for recirculating heating liquid to a tubular jacket 512 which surrounds the heating enclosure 511 of the liquid to be sterilized. The heating chamber 511 and the jacket 512 form a first heat exchanger 51. The main heating means 80 further comprise an adjustable heating member 84 for heating the heating liquid, as well as a pump 42 for continuously circulating the

  heating liquid in the exchanger 51.

  The first pipe 1 has two inputs controlled respectively by means of two valves 20, 21: a first input is connected to a water source (valve 20) and the second

  inlet is connected to a source of medical liquid (valve 21).

  The following members are arranged on the first pipe 1, in order from the valves 20, 21: a conductivity meter 85 for measuring the conductivity of the liquid in the circuit and for checking whether the liquid is water or a solution; a filter 86; a degassing chamber 87 provided with a level detector 88; a flow meter 74; a first pump; first additional heating means 501 and a valve 23. A drain pipe 3, which is provided with a valve 22 and a non-return valve 89, connects a high point of the degassing chamber 87 to the sewer . A bypass line 4 provided with a pump 41 is connected to the purge line 3 so as to bypass the valve 22. In operation, each time the level detector 88 no longer detects liquid, or the valve 22 is open for a determined time if the pressure of the liquid in the circuit upstream of the first pump 40 is greater than atmospheric pressure, or else the pump 41 is put into service for a determined period, if the pressure of the liquid in the circuit in upstream of pump 40 is lower

at atmospheric pressure.

  The second pipe 2 connects the outlet of the heating enclosure 511 to an outlet of the main circuit, which is constituted by a special sterilizable connector 90, having an inlet and two outlets. A connector of this type is for example described in patent No. WO 96/05883. The following members are arranged on the second pipe 2, in order from the exchanger 51: first additional cooling means 502, which are advantageously combined with the first additional heating means 501 to form a second heat exchanger 50 ; main cooling means comprising a tubular jacket 521 surrounding the pipe 2 over a part 522 of its length to form a third heat exchanger 52, the jacket 521 having an inlet connected to a source of cold water by a supply pipe 5 on which is disposed a pump 43, and an outlet connected to the sewer by a discharge pipe 6 on which are arranged, in order from the exchanger 52, a valve 25 and a non-return valve 91 ; first means for adjusting the liquid pressure constituted by a valve 36 with adjustable opening; two valves 26, 27 which are split for safety reasons; and the sterilizable connector 90, which has an inlet connected to the end of the pipe 2, a first outlet (not shown) for connecting the device to a container or to a patient and a second outlet connected to one end of a first evacuation pipe 7, of which

  the other end is connected to the sewer.

  As will be explained later in detail, the first evacuation pipe 7 is used during the sterilization of the second pipe 2 and of the connector 90, and during the drainage of the peritoneal cavity of a patient, when the device according to the The invention is used for the treatment of a patient by peritoneal dialysis. The following members are arranged on the first evacuation pipe 7, in order from the connector 90: two valves 28, 29 which are split for safety reasons; second additional cooling means 531; second means for adjusting the liquid pressure constituted by a valve 37 with adjustable opening, which a bypass line 8, provided with a valve 30, makes it possible to bypass; a non-return valve 92; a second flow meter 75; a blood detector 95; a valve 31. A bypass line 9 provided with a valve 32 and a second pump 44 is connected to the evacuation line 7 so as to bypass the valve 31. As will be explained below in detail, the second pump 44 is used for drainage of the peritoneal cavity of a patient. This second pump can also be used at the start of a step of filling a container or the peritoneal cavity of a patient subjected to a

  treatment with peritoneal dialysis.

  A second discharge line 10 has one end connected to the second line 2 of the main circuit, immediately downstream of the adjustable valve 36, and its other end is connected to the sewer. On this line 10 are arranged, in order from the second line 2, a first valve 33, a second valve 34, and a non-return valve 93. As described in detail below, this line of evacuation 10 is used during peritoneal dialysis treatment, outside the stages of

  filling the patient's peritoneal cavity.

  The first and second evacuation pipes 7 are connected by a connecting pipe 11, having one end connected to the pipe 7, between the valve 29 and the second additional cooling means 531, and its other end connected to the pipe 10, between valves 33 and 34. On this connecting pipe 11 is

arranged a valve 35.

  The device for preparing and dispensing a sterile liquid according to the invention further comprises a third line 12 mounted as a bypass to the first line 1, between a first point located downstream of the first pump 40 and a second point located upstream of the first exchanger 51. On this third pipe 12 are arranged, in order from the pump 40, second

  additional heating means 532 and a valve 24.

  Advantageously, the second additional heating means 532 are combined with the second additional cooling means 531 to form a fourth

heat exchanger 53.

  According to the invention, the third pipe 12 and its accessories, as well as the adjustable valve 37 disposed on the first discharge pipe 7, are part of the device sterilization means (second pipe 2 and connector 90). The device shown in FIG. 1 also comprises a plurality of pressure and temperature measurement means arranged at various points in the main circuit (pipes 1 and 2), the first discharge pipe 7, and main heating means 80. In particular, a pressure sensor is connected to the following pipes, at the following points: on the second pipe 2, between the third exchanger 52 and the first adjustable valve 36 (item 70); - on the second pipe 2, immediately upstream of the connector 90 (item 71); - On the first evacuation pipe 7, between the fourth exchanger 53 and the second adjustable valve 37

(item 72).

  A temperature sensor is connected to the following pipes, at the following points: - on the first pipe 1, immediately downstream of the first pump 40 (item 60); - At the entry and exit of the heating enclosure 511 of the main heating means 80 (references 63, 64); - On the pipe 83 for recirculating the heating liquid, at the outlet of the tank 81 (item 61) and at the outlet of the jacket 512 (item 62); - on the second pipe 2, between the third exchanger 52 and the first adjustable valve 36 (item 65); - on the second pipe 2, at the junction point of this pipe with the second evacuation pipe 10 (item 66); - On the first evacuation pipe 7, at the entrance to the fourth exchanger 53 (item 67); - on the first evacuation pipe 7, downstream of the

  second adjustable valve 37 (item 68).

  The following table indicates the manufacturers and the references of components suitable for the realization of the

Figure 1 device.

  COMPONENT FIGURE 1 MANUFACTURER REFERENCE OF

  REFERENCE No. MANUFACTURER detector 95 HOSPAL DASCO 6,957,989 leak blood chamber 87 HOSPAL DASCO 6,965,925 degassing Conductivity 85 HOSPAL DASCO 6945109 6962195 pump 43 HYDROFLUID gear prototype HOSPAL R & D Pump 41 ASF 6959100péristaltique pump 40, 44 THUTILL B9049PYWQS gear Filter 86 HOSPAL DASCO 6,958,821 Flow 74, 75 HOSPAL DASC0 6955959 Exchanger 50, 51, 52, 53 PARKER FLUID type DHTC SS4 thermal CONNECTOR Detector of 88 HOSPAL DASCO 6957054 level Means of 42, 80, 81, 84 BIOBLOCK type HUBERT heating (G85111) main Pipe 83 PROLABO 06521000 of recirculation Check valve 89, 91, 92, 93 HOSPAL DASCO 6950737 return Connector 90 CAMBRIDGE sterilizable prototype CONSULTANTS Valve with 36, 37 NUPRO type RL3 opening (SWAGELOK) (SS-3K-RL3-VI adjustable Sensor of 70, 71, 72 KELLER PA-10-8838 pressure Solenoid valve 20, 21, 22, 25, SIRAI DlllS15Z612A

31, 32

  Solenoid valve 23, 24, 26, 27, BURKERT type 255

28, 29, 30, 33, (35003999)

  34.35 Line 1, 2, 3, 4, 5, FAURE 36403031 stainless steel 6, 7, 8, 9, 10, AUTOMATION

11, 12

  Sensor of 60, 61, 62, 63, FAURE TC2EJ20M3AJR1 temperature 64, 65, 66, 67, AUTOMATION The device according to the invention also comprises a control unit (not shown). This unit receives the information measured by the pressure sensors 70 to 72, by the temperature sensors 60 to 68 and the flowmeters 74 and 75. From this information, from the set value for the operating parameters communicated by an operator (notably, possibly, the flow rate of the liquid), and from a command and control program stored in a memory of the control unit, this unit controls and monitors the operation of the device. In particular, in accordance with the invention, the control unit controls and validates the sterilization treatment applied on the one hand to the

  liquid, on the other hand to the device.

  According to the invention, to certify that at any time the liquid at the outlet of the main heating means 80 is sterile, it is first necessary to define a parameter representative of the sterilizing value of the treatment used, which can be calculated , for example, from an algorithm modeling the temperature distribution inside the exchanger 51 of the main heating means 80, and from the value of at least one of the parameters likely to influence the treatment sterilization, namely the flow Q of the liquid to be sterilized in the exchanger 51, the temperature of the liquid to be sterilized (Tin) at the inlet of the exchanger 51 and the temperature of the

  heating liquid (THin) at the inlet of the exchanger 51.

  As the temperatures at the outlet of the exchanger 51 (temperatures of the sterile liquid and the heating liquid) are linked to the temperatures at the inlet of the exchanger 51, it is naturally also possible to take the temperature into account in the calculations. outlet (All) of the sterilized liquid and / or outlet temperature (THout) of the heating liquid. When the parameter representative of the sterilizing value of the treatment is defined, a set value for this parameter is then chosen which is both sufficiently high to correspond to effective sterilization of the liquid and as low as possible to prevent or limit degradation of the liquid to be sterilized when the latter is sensitive to heat (case of solutions for

  peritoneal dialysis that contain glucose).

  In operation, the control unit is programmed to calculate at regular intervals the value of the parameter representative of the sterilizing value of the treatment, from the temperature distribution algorithm in the exchanger 51, and temperature and temperature information. flow measured by the corresponding sensors. Each time a new parameter value is calculated, the control unit checks that this calculated value is greater than the value

  and it validates the sterilization of the liquid.

  This control method which makes it possible to validate the effective sterilization of the liquid as resulting from the correct implementation of the device according to the invention can be passive. Indeed, given that the sterile state is a crucial characteristic of a medical liquid to be injected, it is possible to provide a standard operating mode of the sterilization device where the choice of the flow rate of the liquid to be sterilized is limited to a limited number of different predetermined values (for example three) and o all the other operating parameters of the device are preset according to the predetermined flow rates

  that the operation of the device is simplified as much as possible.

  The control method described above is then used

only to validate sterilization.

  Naturally, it is also possible to provide a mode of operation of the device where the choice of the flow rate of liquid to be sterilized is free within a range of determined values. In this case, the control unit can be used to calculate, from the chosen flow rate and the setpoint of the parameter representative of the sterilizing value, the other operating parameters of the device, in particular the temperature of the heating liquid. . In operation, the control unit regularly adjusts the flow rate of the first pump 40 and / or the temperature of the heating liquid, so that the calculated value of the parameter is always greater than the set value. In one embodiment of the invention, the parameter designated in the literature by FO (expressed in minutes) is used as the parameter representative of the sterilizing value of the sterilization process. Recall that F0 is the sum FT of the sterilizing effects accumulated during a sterilization treatment (or "sterilizing value Fz") when the reference temperature T is equal to 250 F (121.1 C) and the value of thermal inactivation Z is 18 F (10 C). For the record, the thermal inactivation value Z is the temperature rise which multiplies by ten the speed of destruction of a specific microorganism. Z = C corresponds to a theoretical microorganism a little more resistant than the microorganism reputed to be more heat resistant than any other spore-forming microorganism, Bacillus stearothermophilus. The canonical formula for F0 is as follows: T-121 FO = Jt 10 10 dt o

D 0

  This formula is not directly applicable to the control of a sterilization treatment o the liquid to be sterilized is in continuous flow and o the heating means used to raise the temperature of the liquid to be sterilized do not carry this liquid at any point of the pregnant

heating to the same temperature.

  According to the invention, when the heating means are arranged to heat the liquid to be sterilized along a portion of the pipe where the liquid is circulated, the following formula can be used to calculate F0: T (y) -121 FO -Lx 10 10 dy o Q in which L = length of the pipe portion (heating enclosure 511) by means of which the liquid to be sterilized is heated by the heating means 80; S = internal section of the heating enclosure 511; Q = flow rate of the liquid to be sterilized in the heating enclosure 511; T (y) = equation of the distribution of the temperature of the liquid as a function of the distance from the inlet of

the heating chamber 511.

  The equation T (y) depends on the structure of the exchanger 51 of the main heating means 80 and on its operating mode. By way of example, reference is made to FIG. 3 which represents a first embodiment of an exchanger adapted to the device of the invention. This exchanger consists of two concentric pipes, the outside pipe forming a jacket 512 around the inside pipe which constitutes the heating enclosure.

511 mentioned above.

  In operation, the liquid to be sterilized and the heating liquid (ethylene glycol) coming from the tank 81 are circulated, against the current, in the internal pipe (heating chamber 511) and in the external pipe (jacket 512). The internal diameter of the heating enclosure 511 is chosen so that, in the range of flow rates o are included the operating flow rates of the sterilization device (for example from 100 to 400 ml / min.), The flow of liquid at sterilize is always turbulent. For an exchanger having an internal stainless steel pipe and an external copper pipe and having the following dimensions: Length (cm) 222 Internal pipe volume (ml) 26 External pipe volume (ml) 105 Internal pipe section (cm2) 0.117 Surface of the annular space between pipe 0.502 internal and external (cm2) Internal perimeter of the internal pipe (cm) 1.213 External perimeter of the internal pipe (cm) 1.995 Internal exchange surface of the pipe 269 internal (cm2) Surface d external exchange of internal pipe 443 (cm2) the equation T (x) can be written as follows: rx [e-ny e-nL T (y) = Tin + (THin -Tin) xre -enL 1-rxe in which: Tin = temperature of the liquid to be sterilized at the inlet of the heating enclosure 511 (as measured by the sensor 63). THin = temperature of the heating liquid at the inlet of the

  jacket 512 (as measured by sensor 61).

  r = 6 x 10-5 x Q2 _ 0.0577 Q + 19.084

! 301 415 -958.18Q + Q 2

n = - ln [

  L 292.6 + 65.72Q-0.200453Q3 +0.00020948

  Q = flow rate of the liquid in the heating chamber 511.

  As appears from this example, it is possible to calculate the sterilizing value F0 at any time, from a measurement of the temperature Tin of the liquid to be sterilized at the inlet of the exchanger 51, from a measurement of the temperature THin of the heating liquid at the inlet of the exchanger 51, of a measurement of the flow rate Q of liquid to be sterilized and of an equation modeling the temperature distribution at

inside the exchanger 51.

  During all the phases of operation of the device according to the invention where the device is programmed to produce a sterile liquid (water or medical liquid) the control unit validates the sterilization treatment implemented by checking that the calculated sterilizing value F0 is always greater than a first threshold value FOminl

  corresponding to the sterility of the liquid.

  According to the invention, during a preliminary phase of operation of the device, it is necessary to sterilize the main circuit of the device, from the exchanger 51 to the connector 90 included, that is to say beyond the connector 90, for example up to the level of the temperature sensor 67 connected to the first sterilization pipe 7. The sterilization of the main circuit can be considered to be effective when all the points of the main circuit downstream of the exchanger 51 have been worn, with sterile liquid, at a minimum temperature of T2 for a minimum time of t2, which corresponds to a second sterilizing value of setpoint FOmin2, such as:

T2-121

  [] FOmin2 = t2 x 10 10 The validation of the sterilization of the main circuit can be carried out simply by the control unit by checking that during an uninterrupted period of time of a duration at least equal to t2, the temperature of the liquid measured by the temperature sensor 67 has constantly been greater than T2. As the sterilization of the device must be carried out with sterile water, during the initial sterilization phase of the device, the control unit must validate both the sterilization of the liquid and the sterilization of the main circuit. In other words, the control unit must check both that the sterilizing value of the sterilization treatment applied to the liquid is greater than F min 1 and that the sterilizing value of the treatment of liquid

  sterilization applied to the circuit is greater than FOmin2.

  When the device is used to administer an automated peritoneal dialysis treatment, the operation of the device essentially comprises the following four phases: The first phase corresponds to the initial sterilization

of the device.

  The second phase corresponds to a waiting state where the device is kept sterile and produces sterile water at low flow rate. This second phase occurs just after the initial sterilization of the device or between two active phases of device operation, filling of the patient's peritoneal cavity and drainage of this cavity

  after the liquid has stagnated there for a determined time.

  The third phase corresponds to the continuous production of the sterile solution to fill the patient's peritoneal cavity. The fourth phase corresponds to the drainage of the peritoneal cavity of the patient while the device is maintained

  sterile and produces low-flow sterile water.

  First phase: initial sterilization of the circuit.

  To save liquid for medical use, the sterilization of the circuit is preferably carried out with water (valve 20 open, valve 21 closed). During this first phase, which comprises several stages, the valve 23 is closed and the valve 24 is open, so that the water circulated by the first pump 40 circulates in the third pipe 12. Furthermore the first adjustable valve 36 is fully open and the second adjustable valve 37 is only partially open so that the pressure in the circuit upstream of the valve is always greater than the pressure at which the water would boil (if the water boiled, it would not be possible to validate the sterilization of the circuit, since it would not be possible to certify that the circuit has been contacted in all points by water having a minimum temperature for a minimum uninterrupted period of time). Pumps 43 and 44 are not

in service.

  In a first step of this first phase, the valves 26, 27, 28, 29, 30, 32, 34 are closed, and the valves 33, 35, 31 are open, so that, downstream of the first adjustable valve 36 , the water flows into a part of the second discharge line 10, in the line of

  link 11, then in the first evacuation pipe 7.

  In a second step of this first phase, the valves 26, 27, 28, 29 are open, so that the water then also flows into the end of the second pipe 2, through the connector 90 and then into the first evacuation pipe 7, as soon as it is connected to the

connector 90.

  In a third stage of the first phase, the valves 33, 35 are then closed, so that the water no longer circulates in the start of the second evacuation pipe 10. The duration of these three stages, as well as the flow of water in the circuit, the degree of opening of the valve 37, and the intensity of the heating provided by the main heating means 80 are either set to preprogrammed values or adjusted according to one another so that the sterilizing value of the sterilization treatment applied to the water and to the circuit is greater than the first and second setpoint values FOmin1, FOmin2. The control unit also verifies that, taking into account the actual operating conditions of the device, as measured by the various sensors, the effective sterilizing value is

greater than FOminl and FOmin2.

  By way of example, during this first phase, the flow of water circulated by the pump 40 is adjusted to 250 ml / min., The pressure in the circuit upstream of the valve 37 is adjusted to seven bars, the ethylene glycol temperature at the inlet of the exchanger 51 is adjusted to 165 ° C. (the pressure in question here, as in the whole document, is the absolute pressure). The temperature of the water at the outlet of the exchanger 51 is then at least equal to 153 C and the temperature upstream of the fourth exchanger 53, as measured by the sensor 67, is at least equal to 131 C. The duration different stages are chosen so that the sterilizing value of the sterilization treatment applied to the liquid is greater than 30 min. and the sterilizing value of the sterilization treatment applied to the circuit is greater than 30 min.

  Second phase: putting the device on hold.

  The main objective of this phase is to have sterile water at a temperature of 37 C and at the pressure

  atmospheric at connector 90.

  In a first step of this second phase, the valve 23 is opened so that the water circulated by the pump 40 flows both into the first pipe 1 and

in the third line 12.

  In a second step, the valve 24 is closed so that the third line 12 is isolated. Furthermore, the valve 25 of the main cooling means is open and the pump 43 is put into service. During this step, the water is cooled in the exchanger 52 from which it leaves about 37 C while the first adjustable valve 36 is gradually closed and the second adjustable valve 37 is gradually opened so that, at no time, the water does not boil, whatever its temperature, and that, when the adjustment of the valves 36, 37 is finished, the pressure upstream of the first adjustable valve 36 is of the order of seven bars and the pressure upstream of the second adjustable valve 37 is of the order of one bar (atmospheric pressure). The valve 30 mounted in bypass on the second

adjustable valve 37 is closed.

  In a third step, the valves 33, 34 are opened, so that the water also flows in the second

drain line 10.

  Finally, in a fourth step, the valves 26, 27, 28, 29 are closed, so that the sterile water only flows in the second discharge line 10 and that the water

  stagnates in the circuit portion comprising the connector 90.

  In this mode of operation of the device, which is a standby mode, all the sterile water is sent to the sewer. For reasons of economy, the flow rate of the pump 40 is reduced as much as possible, that is to say to a value (100 ml / min.) O the flow of water in the heating enclosure. 511 remains turbulent. Preferably, the temperature of the heating liquid of the main heating means 80 is lowered accordingly. During this second phase, as in the following phases, the control unit checks at regular time intervals that the sterilizing value F0 of the treatment applied to water, as calculated from the measured values of the flow Q and temperatures Tin, THin at the inlet of the exchanger 51, is always within a range of values having the first setpoint value FOminl as the lower limit (for example between 30

min. and 40 min.).

  Third phase: production of sterile medical liquid.

  The objective of this third phase is to produce a sterile medical liquid and to perfuse this liquid in the patient's peritoneal cavity. A first step consists in closing the valve 20 and in opening the valve 21 which gives access to a source of medical liquid to be sterilized so that the medical liquid replaces the water in the first line 1, in the second line 2 until the first valve

  adjustable 36, and in the second discharge line 10.

  The second step of the third phase consists in opening the valves 26, 27, 28, 29, 31 so that the sterile medical liquid replaces the water in the end of the second pipe 2, the connector 90 and the first pipe d 'evacuation 7. Then the valves 33, 34 are closed, so that the liquid is no longer routed to the sewer by

  the first evacuation pipe 7.

  The third step consists in connecting the patient to be treated to the device by means of a flexible pipe (not shown), having one end connected to the catheter of the patient and another end connected to the connector 90 of the device. During the three preceding steps, the flow rate of the medical liquid controlled by the pump 40 is adjusted to a set perfusion rate suitable for the patient. After the patient has been connected to the device, the flow of liquid at the outlet of the connector 90 (infusion rate) is controlled by the comparison between the pressure measured by the pressure sensor 71 and a set pressure corresponding to an admissible pressure for the patient. To vary the infusion rate, a first possibility consists in modifying the rate of the first pump 40, which may require correspondingly modifying the temperature of the heating liquid. In order not to have to vary the sterilization parameters (liquid flow rate, temperature of the heating liquid) another possibility consists in opening the valves 28, 29, 32, in closing the valve 31 and in

  pilot the second pump 44 at the appropriate flow rate.

  According to a variant of the invention, the filling of the patient's peritoneal cavity is not carried out at a constant rate as soon as the patient connects to the device and the infusion at nominal rate is preceded by a transient phase where the rate is gradually increased until the nominal flow rate is reached. In order to be able to vary the infusion rate without having to modify the rate of the first pump 40 (that is to say also the parameters for sterilizing the liquid), the first evacuation pipe 7 and the second pump 44 are used. to withdraw from the connector 90 and send to the sewer a decreasing fraction of the liquid sterilized by the device. To do this, before the patient is connected to the device, the valves 28, 29, 30, 32 are open, the valve 31 is closed, and the second pump 44 is put into service at the same rate as the main pump 40. When the patient is connected to the device, the second pump 44 is controlled so that its flow decreases

  gradually until it becomes zero (pump 44 stopped).

  This filling phase ends either when a predetermined quantity of liquid, calculated using the information supplied by the flow meters 74 and 75, has been perfused, or when the pressure measured by the pressure sensor 71 reaches a predetermined pressure. In the latter case, the control unit calculates using the information provided by the flow meters 74, 75 the quantity

total of infused fluid.

  Fourth phase: drainage of the patient's peritoneal cavity. This phase follows the waiting phase described above, during which the device produces sterile water at a low flow rate to maintain the sterility of the device, this sterile water being sent to the sewer by the second pipe d evacuation 10. Therapeutically, the drainage of the peritoneal cavity of the patient is controlled when the liquid perfused during the previous filling phase has stagnated in the peritoneal cavity during a

predetermined duration.

  Relative to the waiting phase, the valves 28, 29, 30, 32 are open and the pump 44 is put into service at a predetermined flow rate. The pump 44 is stopped when the amount of liquid drained is equal to the amount of liquid previously infused, increased by an amount of liquid corresponding to the weight that the patient must lose during each phase of stagnation. Alternatively, the pump 44 is stopped when the pressure measured by the pressure sensor

  pressure 71 reaches a determined low threshold value.

  At the end of this drainage phase, the valve 20 is closed and the valve 21 is opened so that the device

  sterilizes medical fluid again.

  FIG. 2 represents a second embodiment of the device according to the invention. This device essentially comprises main heating means 80 having a heating enclosure 511 for the liquid, and a main circuit having a first pipe 1 connected to an inlet of the heating enclosure 511 and a second pipe 2 connected to an outlet of the enclosure of

heating 511.

  The main heating means 80 comprise a tank 81 containing a heating liquid, such as oil or ethylene glycol. The heating enclosure 511, which is shaped in a helix, is arranged in the tank 81 so as to be immersed in the heating liquid. An adjustable heating element 84 makes it possible to raise the temperature of the heating liquid. The heating means 80 further comprise means for homogenizing liquid constituted by a pipe 83 connecting the lower part to the upper part of the tank 81, on which is disposed

a pump 42.

  The first pipe 1 has an inlet which can be connected either to a source of water or to a source of medical liquid. The following members are connected to the first pipe 1, in order from the entry of the pipe 1: a flow meter 74; a first pump 40; a valve 23; first and second heating means

additional 541, 551.

  The second pipe 2 connects the outlet of the heating enclosure 511 to an inlet of a sterilizable connector 90,

  having a first outlet for dispensing the sterile liquid.

  The following members are connected to the second pipe 2, in order from the main heating means 80: first additional cooling means 552, which are advantageously combined with the second additional heating means 551 to form a first heat exchanger 55; second additional cooling means 542, which are advantageously combined with the first additional heating means 541 to form a second heat exchanger 54; main cooling means 56; a valve 27; first pressure regulation means 36, constituted by a valve calibrated to a first

  pressure threshold (five bars); and a valve 26.

  The heat exchangers 54, 55 are preferably shaped like the exchanger shown in FIG. 4, namely by the junction over part of their length of the pipe 1 and of the pipe 2. The two portions of contiguous pipes are shaped to form a helix with contiguous turns, and the inside and the outside of the cylinder thus formed are covered with a good material

conductor of heat.

  The main cooling means 56 comprise a reservoir 57 having an inlet connected to a source of cold water by a pipe 5 and an outlet connected to the sewer by a pipe 6 on which is disposed a valve 25. A drain pipe 15 provided with a valve 39 is connected to the pipe 5 to allow the emptying of the tank 57 by gravity when the supply of the pipe 5 with cold water is interrupted and the valves 25 and 39 are open. Line 2 comprises a portion 522 shaped as a helix, which is arranged in tank 57 so as to be immersed in cold water. The cooling means 56 are further provided with liquid homogenization means constituted by a recirculation line 58 connecting the lower part to the upper part of the tank 57, on which a pump 43 is arranged. In operation, the pump 43 rotates permanently, and the temperature of the water in line 2 downstream of the cooling means, which is measured by a temperature sensor 65, is compared to a reference temperature: when the temperature of the water in line 2 exceeds the reference temperature, the valve 25 is open until the temperature of the water in line 2 has dropped below the

reference temperature.

  The sterilization device shown in FIG. 2 also comprises a first evacuation pipe 7 which is connected to a second outlet of the connector 90, as well as a second evacuation pipe 10 which is connected

  to the second line 2 of the main circuit.

  The first evacuation pipe 7 is used for drainage of the peritoneal cavity of a patient, when the device according to the invention is used for the treatment of a patient by peritoneal dialysis; it is also used, partially, during the sterilization of the second pipe 2 and of the connector 90. The following members are connected to the first discharge pipe 7, in order from the connector 90: a first valve 28; a second valve 32; a second flow meter 75; a third

valve 35; and a pump 44.

  The second discharge line 10 has one end connected to the second line 2 of the main circuit, between the calibrated valve 36 and the valve 26, and its other end is connected to the sewer. The second evacuation pipe, on which a first valve 33 and a second valve 34 are arranged, is used during a peritoneal dialysis treatment, apart from the infusion steps of the

patient.

  The first and second evacuation pipes 7, 10 are connected by a connecting pipe 11, having one end connected to the pipe 7, between the valves 28 and 32 and its other end connected to the pipe 10, between the valves 33 and 34. On this connecting pipe

11 is arranged a valve 29.

  The device shown in FIG. 2 further comprises means used specifically for the sterilization of the second pipe 2 of the main circuit and of the connector, namely a third pipe 12 mounted as a bypass to the first pipe 1, and a fourth pipe 13 mounted in derivation to the second

drain line 10.

  The third pipe 12 has one end connected to the first pipe 1 between the pump 40 and the valve 23 and its other end connected to the first pipe 1 between the two heat exchangers 54, 55. On this third pipe 12 are arranged, in the direction of circulation of the liquid, a valve 24 and third means

additional heating 532.

  The fourth pipe 13 has one end connected to the second discharge pipe 10 between the valves 33 and 34 and its other end connected to the pipe 10 downstream of the valve 34. On this fourth pipe 13 are connected, in the direction of circulation of the liquid, third additional cooling means 531, second pressure regulation means constituted by a valve 37 calibrated at a second pressure threshold (three bars) and a valve 31. Advantageously, the third additional heating means 532 are combined with the third additional cooling means 531 to form a heat exchanger 53 shaped like the exchanger shown

in figure 4.

  Like the device in FIG. 1, the device shown in FIG. 2 further comprises a plurality of pressure and temperature measurement means arranged at various points in the main circuit (pipes 1 and 2), of the first evacuation pipe. 7, main heating means 80 and main cooling means 56. In particular, a pressure sensor is connected to the following pipes, at the following points: - on the first pipe 1, between the valve 23 and the second exchanger 54 ( item 70); - on the first evacuation pipe 7, between the

valves 32 and 35 (item 71).

  A temperature sensor is connected to the following pipes, at the following points: - on the first pipe 1, at the outlet of the heating enclosure 511 of the main heating means 80 (item 64); - on the pipe 83 for recirculating the heating liquid (item 62); - on the coolant recirculation line 58 (item 60); - on the second pipe 2, between the main cooling means 56 and the valve 36 calibrated at one

  first pressure threshold (item 65).

  The device shown in Figure 2 further includes a command and control unit (not shown). This unit receives the information measured by the pressure sensors 70, 71, the temperature sensors 60, 62, 64, 65 and the flow meters 74 and 75. From this information, operating parameters communicated by an operator, and d calculation algorithms and control programs stored in a memory, the control unit commands and controls the

  different operating phases of the device.

  The operation of this device is not fundamentally different from the operation of the device

shown in figure 1.

  During the sterilization phase of line 2 and connector 90, the main cooling means 56 are out of service: the pump 43 is stopped, the valves 25 and 39 are open and the cold water supply to line 5 is interrupted by so that the tank 57 is empty. The valves 24, 26, 27, 28, 29, 31 are open and the valves 23, 32, 33, 34, 35 are closed. When the circuit comprising the pipe 2 and the connector 90 has been sterilized, the portion of the pipe 10 between the pipe 2 and the pipe 11 is in turn sterilized. To this end, the valve 33 is open and one of the valves 26, 28, 29 is closed. For example, the pressure in the main circuit between the pump 40 and the valve 36 calibrated at the first pressure value is five bars, the pressure between the valve 36 and the valve 37 calibrated at the second pressure value is three bars and the pressure downstream of the valve 37 is one bar (atmospheric pressure). The temperature of the heating liquid is adjusted so that, for an adequate configuration of the heating means and for an appropriate flow rate, the temperature of the water in the pipe 12 downstream of the third exchanger 53 is 110 ° C., the temperature of the water at the outlet of the heating enclosure 511 is 150 C, the temperature of the water downstream of the first and second exchangers 54, 55 and upstream of the third exchanger 53 is 130 C, and the temperature of the water in line 13 downstream of the third exchanger 53 is 60 C. The time at which the second pipe 2 and the connector 90 are left in contact with sterile water at 130 C is sufficient to guarantee their sterility, this is that is to say also that the sterilizing value F0 of the sterilization treatment applied to them is greater than the second threshold value FOmin2. During the waiting phase when the device is kept sterile, the valves 23, 27, 33, 34 are open and the valves 24, 26, 28, 29, 31, 32, 33, 35 are closed. The main cooling means 56 are in service (pump 43 in operation, valve 39 closed, valve 25 open intermittently). During the liquid perfusion phase, the valves 23, 26, 27, 28, 32 are open and all the other valves are closed. The main cooling means 56 are in service (pump 43 in operation, valve 25 intermittently open). For example, during these last two phases, the pressure in the main circuit between the pump 40 and the valve 36 calibrated at the first pressure value is five bars and the pressure downstream of the valve 36 is one bar (atmospheric pressure). The temperature of the heating liquid is adjusted so that, for an adequate configuration of the heating means, the temperature of the water leaving the heating chamber 511 is 150 ° C., the temperature of the water downstream first and second heat exchangers 54, 55 or 60 C, and the temperature of the water

  downstream of the main cooling means is 37 C.

  For liquid flow rates less than or equal to approximately 300 ml / min., The operating conditions which have just been mentioned make it possible to guarantee that the water or the medical liquid produced by the device is sterile. In other words, the sterilizing value F0 of the sterilization treatment applied to water or medical liquid is

  greater than the first threshold value FOminl.

  The invention is not limited to the exemplary embodiments which have just been described and it is susceptible of variants.

Claims (43)

  1. Device for preparing a sterile liquid comprising: - adjustable main heating means (80) for raising the temperature of a liquid inside a heating enclosure (511), - a main circuit comprising: * a first pipe (1) having one end connectable to a source of liquid to be sterilized and another end connected to an inlet of the heating enclosure (511), and * a second pipe (2) having one end connected to a outlet from the heating enclosure (511) and another end connected to a connector (90) having a first outlet for delivering a sterile liquid, - first pumping means (40) for circulating the liquid in the main circuit ( 1, 2), characterized in that it comprises: - means for validating a sterilization treatment applied to the liquid comprising calculation means for calculating a parameter representative of the sterilizing value (F0) the sterilization treatment from the value of at least one operating parameter of the device (Q, Tin, THin, All, THout), and comparison means for comparing the calculated value of the parameter representative of the sterilizing value (F0 ) at a first threshold value FOmin1 corresponding to the sterility of the liquid. 2. Device according to claim 1, characterized in that it further comprises control means for controlling the pumping means (40) and / or the heating means (80) so that the calculated value of the parameter representative of the sterilization value (F0) is greater than the first threshold value FOminl.   3. Device according to one of claims 1 and 2, characterized   in that the calculation means are provided for calculating the parameter representative of the sterilizing value (F0) of the sterilization treatment applied to the liquid from a mathematical model of the distribution of temperatures in the heating enclosure (511), the temperature (Tin, All) of the liquid entering or leaving the heating chamber (511), the temperature of the heating liquid (THin) and the flow rate of the liquid (Q) in the chamber of heating (511).   4. Device according to claim 3, characterized in that the parameter representative of the sterilizing value (F0) of the sterilization treatment applied to the liquid is the sterilizing value F0, defined by: T (y) - 121 -'1 Fo = | - xl 10 dy FO = fL Sx 10 o Q o - L is the length of the heating enclosure (511); - S is the section of the heating enclosure (511); - Q is the flow rate of the liquid in the heating chamber (511);   - T (y) is an equation of the temperature distribution in the heating chamber (511).   5. Device according to one of claims 1 to 4, characterized   in that it further comprises means (36, 37) for preventing the formation of bubbles in the liquid during the liquid sterilization.   6. Device according to claim 5, characterized in that the means for preventing the formation of bubbles in the liquid during the production of sterile liquid comprise first means (36) for adjusting the pressure of the liquid to a pressure value greater than the vaporization pressure of the liquid, whatever the temperature of the liquid, the first liquid pressure adjustment means (36) being disposed on the second pipe (2) of the main circuit.   7. Device according to one of claims 1 to 6, characterized   in that it further comprises a first evacuation pipe (7) connected to a second outlet of the connector (90).   8. Device according to one of claims 1 to 7, characterized   in that it further comprises a second discharge line (10) connected to the second line (2) of the main circuit between the first means for adjusting the   pressure (36) and the connector (90).   9. Device according to one of claims 1 to 8, characterized   in that it comprises first means (501; 541, 551) for additional heating of liquid arranged on the first   main circuit pipe (1).   10. Device according to one of claims 1 to 9, characterized   in that it comprises main cooling means (5, 6, 43, 521; 56) of liquid arranged on the second pipe (2) of the main circuit upstream of the first   pressure adjusting means (36).   11. Device according to one of claims 1 to 10,   characterized in that it comprises means (502; 542, 552) for additional cooling of liquid arranged on the second pipe (2) of the main circuit upstream of the main cooling means (5, 6, 43, 521; 56) liquid.   12. Device according to one of claims 1 to 11,   characterized in that it further comprises means (12, 37, 532; 12, 13, 37, 532) for sterilizing the second pipe   (2) and the connector (90) for delivering the sterile liquid.   13. Device according to claim 12, characterized in that the means for sterilizing the second pipe (2) and the connector (90) comprise second additional heating means (532) of liquid disposed on a pipe (12) mounted in bypass to the first   main circuit pipe (1).   14. Device according to claim 13, characterized in that the first additional liquid heating means arranged on the first pipe (1) of the main circuit comprise two elements (541, 551) and in that the downstream end of the pipe bypass (12) is connected to the first pipe (1) between the two elements (541, 551)   first additional heating means.   15. Device according to one of claims 12 to 14,   characterized in that the means for sterilizing the second line (2) and the connector (90) comprise means (37) for preventing the formation of bubbles in the liquid during the sterilization of the second line (2) and the connector (90).   16. Device according to claim 15, characterized in that the means for preventing the formation of bubbles in the liquid during the sterilization of the second pipe (2) and of the connector (90) comprise second means (37) for regulating the pressure liquid at at least one pressure value greater than the vaporization pressure of the liquid, regardless of the temperature of the liquid, these liquid pressure adjustment means being arranged on the first evacuation pipe (7).   17. Device according to one of claims 12 to 16,   characterized in that the means for sterilizing the second pipe (2) and the connector (90) comprise means for validating a sterilization treatment applied to the   second pipe (2) and to the connector (90).   18. Device according to claim 17, characterized in that the validation means comprise: * calculation means for calculating a parameter representative of the sterilizing value (F0) of the sterilization treatment from a minimum value T of the temperature of the liquid, measured for a determined period of time t, at a point on the first evacuation pipe (7), and * means for comparing the calculated value of the parameter representative of the sterilizing value (F0) with a second value of FOmin2 threshold corresponding to the sterility of the   second pipe (2) and connector (90).   19. Device according to claim 18, characterized in that it further comprises control means for controlling the pumping means (40) and / or the main heating means (80) so that the calculated value of the parameter representative of the sterilizing value (F0) of the sterilization treatment applied to the second pipe (2) and to the connector (90) is greater than the second threshold value F0min2. 20. Device according to claim 18, characterized in that the parameter representative of the sterilizing value (F0) of the sterilization treatment applied to the second pipe (2) and to the connector (90) is the sterilizing value F0, defined by: iT -121 FO = t xlO 10 10 o - T = minimum value of the liquid temperature - t = period of time t during which the minimum value T   of the liquid temperature is measured.   21. Device according to claims 6 and 16, characterized   in that the first and second means for adjusting the liquid pressure consist of first and second valves (36, 37) with variable opening and in that the control means are provided for controlling, at the end of '' a step of sterilizing the first pipe (2) and the connector (90), the partial progressive closing of the first valve (36) and the total progressive opening of the second valve (37).   22. Device according to claim 7, characterized in that it comprises second pumping means (44) arranged on   the first evacuation pipe (7).   23. Device according to claim 22, characterized in that, at an initial stage of an operating phase of the device, the control means are provided for controlling the first pumping means (40) so that the flow of liquid in the main circuit (1, 2) is substantially constant and the second pumping means (44) so that the flow of liquid in the first evacuation pipe (7) decreases progressively, so that the flow of liquid flowing through the first connector output (90) gradually increases.   24. Device according to one of claims 1 to 23,   characterized in that the main heating means (80) adjustable for raising the temperature of a liquid inside the heating enclosure (511) comprise: - a reservoir (512, 81) for containing a heating liquid wherein the heating enclosure (511) is immersed; - Means (84) for raising the temperature of the heating liquid. 25. Device according to claim 24, characterized in that the main heating means (80) further comprise homogenization means (42, 58, 83) to keep the temperature of the heating liquid substantially constant   along the heating enclosure (511).   26. Device according to one of claims 24 and 25,   characterized in that the heating enclosure (511) is a pipe and in that the reservoir (512) for the heating liquid is a pipe concentric with the enclosure heating (511).   27. Method for sterilizing and dispensing a liquid by means of a device comprising: - adjustable main heating means (80) for raising the temperature of a liquid inside a heating enclosure (511), - a main circuit comprising: * a first line (1) having one end connectable to a source of liquid to be sterilized and another end connected to an inlet of the heating enclosure (511), and * a second line (2) having one end connected to an outlet of the heating enclosure (511) and another end connected to a connector (90) having a first outlet for delivering sterile liquid, - an evacuation pipe (7) connected to a second outlet the connector (90), characterized in that it consists in: - heating the liquid in the heating enclosure (511) to a temperature and for a time suitable for sterilizing the liquid; - validate the sterilization treatment applied to the liquid by calculating a parameter representative of the sterilizing value (F0) of the sterilization treatment from the value of at least one operating parameter of the device (Q, Tin, THin, All, THout ), and by comparing the calculated value of the parameter representative of the sterilizing value (F0) with a first threshold value FOminl   corresponding to the sterility of the liquid.   28. The method of claim 27, characterized in that it further comprises controlling the pumping means (40) and / or the heating means (80) so that the calculated value of the parameter representative of the sterilization value ( F0)   is greater than the first threshold value FOminl.   29. Method according to one of claims 27 and 28, characterized   in that it consists in calculating the parameter representative of the sterilizing value (F0) of the sterilization treatment applied to the liquid from a mathematical model of the distribution of the temperatures in the heating enclosure (511), of the temperature (Tin, All) of the liquid entering or leaving the heating chamber (511), the temperature of the heating liquid (THin) and the flow of the   liquid (Q) in the heating chamber (511).   30. Method according to claim 29, characterized in that the parameter representative of the sterilizing value (FO) of the sterilization treatment applied to the liquid is the sterilizing value F0, defined by: T (y) -121 FO = JL S x 10 10 dy o Q o - L is the length of the heating enclosure (511); - S is the section of the heating enclosure (511); Q is the flow rate of the liquid in the heating chamber (511);   - T (y) is an equation of the temperature distribution in the heating chamber (511).   31. Method according to one of claims 27 to 30, characterized   in that it further consists in preventing the formation of   bubbles in the liquid during sterilization of the liquid.   32. Method according to claim 31, characterized in that it consists in pressurizing a part of the main circuit (1, 2) connected to the heating enclosure (511) so that, whatever the temperature of the liquid, the liquid pressure is always higher than the vaporization pressure of the liquid.   33. Method according to one of claims 27 to 32, characterized   in that it further consists in sterilizing the second pipe (2) and the connector (90), bringing in contact with the second pipe (2) and the connector (90) a sterile liquid at a temperature and for a time clean   to sterilize this pipe (2) and this connector (90).   34. Method according to claim 33, characterized in that it also consists in preventing the formation of bubbles in the liquid during the sterilization of the second pipe (2) and of the connector (90). 35. Method according to claim 34, characterized in that it consists in pressurizing at least the second pipe (2), the connector (90) and part of the discharge pipe (7) so that, whatever liquid temperature, liquid pressure is always higher than   the vaporization pressure of the liquid.   36. Method according to one of claims 33 to 35, characterized   in that it also consists in validating the sterilization treatment applied to the second pipe (2) and to the connector (90).   37. Method according to claim 36, characterized in that it consists, to validate the sterilization treatment applied to the second pipe (2) and to the connector (90), - to calculate a parameter representative of the sterilizing value (F0) of the sterilization treatment from a minimum value T of the temperature of the liquid, measured for a determined period of time t, at a point in the first evacuation pipe (7), and - to compare the calculated value of the parameter representative of the sterilizing value (F0) at a second threshold value F0min2 corresponding to the sterility of the second   pipe (2) and connector (90).   38. Method according to claim 37, characterized in that it consists in controlling the pumping means (40) and / or the main heating means (80) so that the calculated value of the parameter representative of the sterilizing value (F0) sterilization treatment applied to the second pipe (2) and to the connector (90) either   greater than the second threshold value F0min2.   39. Method according to one of claims 37 and 38, characterized   in that the parameter representative of the sterilizing value (FO) of the sterilization treatment applied to the second pipe (2) and to the connector (90) is the sterilizing value F0, defined by: T-121 [- FO = txlO 10 o - T = minimum value of the liquid temperature - t = period of time during which the minimum value T   of the liquid temperature is measured.   40. Method according to claims 32 and 35, characterized in   what it consists in pressurizing the part of the main circuit (1, 2) connected to the main heating means (80) by means of a first valve (36) with variable opening, and in pressurizing at least the second pipe (2 ), the connector (90) and part of the evacuation pipe   (7) by means of a second valve (36) with variable opening.   41. Method according to claim 40, characterized in that it consists in controlling, at the end of a sterilization step of the first pipe (2) and the connector (90), the partial progressive closing of the first valve ( 36) and   total progressive opening of the second valve (37).   42. Method according to one of claims 27 to 41, characterized   in that it consists, at an initial stage of a phase of production of sterile liquid, in causing a flow of the liquid in the main circuit (1, 2) at substantially constant flow, and in causing a flow of liquid in the evacuation pipe (7) at a progressively decreasing flow rate, so that the liquid flow rate available at the first outlet from the connector (90) gradually increases.   43. Method according to one of claims 27 to 42, characterized   in that the flow rate of the liquid to be sterilized is chosen so that the flow of the liquid is turbulent in the enclosure of heating (511).