EP2206098A1 - Device for simulating the stomach of a monogastric mammal or of a human being - Google Patents

Device for simulating the stomach of a monogastric mammal or of a human being

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Publication number
EP2206098A1
EP2206098A1 EP08870218A EP08870218A EP2206098A1 EP 2206098 A1 EP2206098 A1 EP 2206098A1 EP 08870218 A EP08870218 A EP 08870218A EP 08870218 A EP08870218 A EP 08870218A EP 2206098 A1 EP2206098 A1 EP 2206098A1
Authority
EP
European Patent Office
Prior art keywords
chamber
block
contents
compression
flange
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP08870218A
Other languages
German (de)
French (fr)
Inventor
Monique Alric
Sylvain Georges Jean Denis
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Universite Clermont Auvergne
Original Assignee
Universite Clermont Auvergne
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Universite Clermont Auvergne filed Critical Universite Clermont Auvergne
Publication of EP2206098A1 publication Critical patent/EP2206098A1/en
Withdrawn legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G09—EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
    • G09B—EDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
    • G09B23/00—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes
    • G09B23/28—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes for medicine
    • G09B23/30—Anatomical models
    • G09B23/32—Anatomical models with moving parts
    • G—PHYSICS
    • G09—EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
    • G09B—EDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
    • G09B23/00—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes
    • G09B23/36—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes for zoology

Definitions

  • the invention relates to a device for simulating a stomach of a monogastric mammal or a human being.
  • Such a device makes it possible to study, in vitro, the digestion of foods as well as the behavior of certain ingested or ingestible products, for example dietary supplements, xenobiotics, pathogens or medicaments.
  • the studies carried out using such a device make it possible to assess the effects of the conditions prevailing in the stomach on these products, for example the time taken by a solid compound to be degraded into sufficiently fine particles to continue its journey through intestine, the kinetics of release of active compounds, the interactions between various products subjected to the gastric environment, and / or the survival of microorganisms.
  • Such a device must, to be representative of the gastric environment, have certain characteristics and perform several functions.
  • the device must have a useful volume adapted to ensure efficient simulation of gastric digestion phenomena.
  • the device must maintain the contents at a temperature between 35 ° C and 45 ° C, and whose pH varies between 1 and 8 approximately.
  • the device At any time during normal operation of the device, it must be able to feed it and inject substances similar to those secreted by a monogastric mammal or a human being, in the stomach, in response to the ingestion of a bowl. food.
  • Such a device must simulate the gastric tone, that is to say ensure mixing and non-aggressive grinding of the liquid and / or solid content of the device. It must also reproduce the gastric transit.
  • the latter comprises the filling of the device, with a control of the arrival of the bolus, a period of residence of the bowl in the device and a controlled and differentiated emptying of the gastric contents towards the small intestine according to the particle size of the content of the device, the liquid components being evacuated first.
  • liquid components denotes either water or solutions, charged or not, the charge solutions comprising so-called fine particles, whose diameter is less than about 5 millimeters.
  • solid components are any particle with a diameter greater than about 5 millimeters.
  • all these variables can be parameterized according to the mammal or the simulated human being and / or the physiological or pathological conditions to be reproduced.
  • WO-A-94/09895 discloses a device comprising two compression chambers interconnected by an intermediate chamber. These compression chambers each house a flexible closed pocket. A fluid injected alternately into one or the other chamber, in the space provided between the inner wall of the compression chamber and the outer wall of the flexible bag, makes it possible to compress the bags selectively. These alternating movements of compression and relaxation of each pocket are supposed to reproduce the stomach contractions.
  • compression and relaxation of the pockets do not ensure optimal mixing of the food bolus with products simulating gastric secretions. Dead zones exist in which there is no satisfactory simulation of gastric digestion.
  • the device described in WO-A-94/09895 can only have a discontinuous operation, that is to say that its initial filling is done at once, at the beginning of the cycle. Such a functioning is not in conformity with the physiological reality since the arrival of the alimentary bolus in the stomach is progressive and lasts the time of a meal.
  • WO-A-2007/010238 discloses an apparatus for simulating gastric digestion comprising two parts, each reproducing an area of the stomach.
  • the apparatus comprises a conical, flexible upper portion connected to a rigid lower portion. This lower part is formed of two concentric cylinders, the inner cylinder receiving a piston.
  • the food bowl passes from the top to the bottom by a passage provided with a non-return valve.
  • the food bowl fills the volume released in the inner cylinder by displacement of the piston.
  • the bolus of food passes in force, by an opening of the inner cylinder, in the light of the outer cylinder. This allows grinding of the particles.
  • the invention more particularly intends to remedy, by proposing a device for simulating a stomach without a dead zone, representative of the overall operation of a stomach of a monogastric mammal or of a human being who allows the introduction of controlled products and / or withdrawal during digestion and ensures a homogeneous mixture of the contents of the device.
  • the subject of the invention is a device for simulating a stomach of a monogastric mammal or of a human being, comprising at least two compression chambers interconnected by an intermediate chamber, characterized in that each compression chamber comprises a piston adapted to push the contents of a compression chamber towards the other compression chamber and in that it comprises means capable of causing a turbulent flow of the contents of the device during its passage through room intermediate formed in an intermediate block equipped with at least one means of access to the intermediate chamber for a product supply and / or withdrawal of the contents of the device at any time during the operating cycle of the device.
  • Such a device allows effective agitation and homogenization of the contents of the device simulating gastric content. Due to the presence of a piston in each compression chamber, such a device has no dead zone.
  • the device may incorporate one or more of the following features:
  • Each piston is movable in a direction parallel to a longitudinal axis common to the two compression chambers and forms a movable bottom to each chamber.
  • the intermediate chamber comprises two cavities of different shapes and sizes.
  • a first cavity is cylindrical with circular section and a second cavity is configured in L, a branch is connected to the first cavity and the other branch is non-emerging in the compression chambers, in normal operation of the device.
  • the means capable of causing the turbulent flow comprise at least one sealing flange mounted between one end of a compression chamber and one end of the intermediate chamber.
  • This flange is provided with at least one calibrated orifice for passing the contents of the device, a compression chamber to the intermediate chamber and vice versa.
  • the sealing flange is arranged so that its orifices are facing a cylindrical cavity of the intermediate chamber.
  • the intermediate block comprises an access port for the introduction of a pH probe and / or temperature in the intermediate chamber.
  • the intermediate block comprises an access port for the introduction of a pressure sensor into the intermediate chamber.
  • the complementary block defining the complementary chamber is interposed removably between the flange and the intermediate block.
  • the complementary block comprises an orifice adapted to receive an accessory for containing a product to be tested.
  • FIG. 1 is a simplified perspective view of a first embodiment of a device according to the invention equipped with a complementary block
  • FIGS. 2 and 3 are longitudinal sections of the device of FIG. 1 respectively in the direction of the arrows H-II and III-III,
  • FIG. 4 is a section along the line IV-IV in FIG. 2;
  • FIG. 5 is a perspective view, on a larger scale, of an accessory intended to contain a product, in the device of FIGS. at 3,
  • FIG. 6 is a front view, on a larger scale than FIGS. 1 to 3, of a closure flange situated between a compression chamber and a complementary block of the device represented in FIGS. 1 to 3,
  • FIG. 7 is a view similar to FIG. 1, of a second embodiment of the device, the latter not being equipped with a complementary block and - Figure 8 is a longitudinal section of the device of Figure 7 according to the arrows VIII-VIII.
  • the device 1, shown in FIGS. 1, 2, 3, 7 and 8, comprises two compression chambers C 2 , C 3 .
  • These chambers are delimited by cylindrical sleeve 2 and 3 tubular cylindrical and, preferably on at least a portion, made of a transparent material, chemically and biologically neutral and easily sterilizable, for example glass or polymethacrylate.
  • a transparent material for example glass or polymethacrylate.
  • Such a transparent material makes it possible to visually monitor the contents of chambers C 2 and C 3 .
  • the sleeves 2 and 3 are inserted into correspondingly shaped orifices formed in square plates 4a, 4b, 4c, 4d.
  • rods 5 connect the angles of the plates 4 to an intermediate block 8, called the main block, of generally cubic shape and which delimits an intermediate chamber C 8 , called the main chamber.
  • the plates 4a to 4d and the rods 5 thus form a frame for holding and protecting the sleeves 2, 3.
  • an end plate 4a, 4d, respectively, is provided with a central orifice allowing the passage of a cylinder 6 2 , 63.
  • the passage of each cylinder 6 2 , 63 is carried out in a sealed manner, the inside of the chambers C 2 , C 3 remaining isolated from the outside.
  • the cylinders 6 2 , 6 3 are advantageously hydraulic or electric type.
  • Each cylinder 6 2 , 6 3 respectively moves a piston 7 2 , 7 3 .
  • Each piston is movable in a direction parallel to a longitudinal axis AA 'common to the chambers C 2 , C 3 .
  • Each piston 7 2 , 7 3 forms an end or movable bottom 7 2 , 7 3 of the chamber C 2 , C 3 in which it is installed.
  • the plates 4a to 4d, the pistons 7 2 , 73 and the cylinders 6 2 , 6 3 and advantageously other component parts of the device 1, are made of a rigid material, chemically and biologically neutral and easily sterilizable.
  • each piston 7 2 , 7 3 The stroke of each piston 7 2 , 7 3 is adapted so that it moves, in each chamber C 2 , C 3 , respectively of an end 21, 31 of the chamber C 2 , C 3 close to a plate 4a, 4d towards the other end respectively 22, 32 near the block 8, and vice versa.
  • each piston 7 2l 7 3 The stroke of each piston 7 2l 7 3 is effected while preserving the tightness in each compression chamber C 2 , C 3 .
  • each piston 7 2 , 7 3 can move independently of the other at an adjustable speed and frequency.
  • the compression chambers C 2 , C 3 are connected at their ends 22 and 32 to the main chamber Cs.
  • the end 22 of the chamber C 2 is adapted to ensure the passage of the contents of the chamber C 2 to the main chamber C 8 .
  • This end 22 is delimited by a plate or flange closure
  • This flange 20 shown in front view of FIG. 6, receives the end of the sleeve 2 in a circular groove 201. When it is at the end of the stroke, the piston 7 2 bears on the flange 20.
  • the closure flange 20 comprises four through-holes and circular, 202, 203, 204, 205, which allow the passage of the contents of the chamber C 2 towards or from the main chamber C 8 .
  • the number of through holes of the flange 20 is different from four, being greater than or equal to one.
  • the orifices 202 to 205 are arranged in the vicinity of an edge of the flange 20.
  • Two orifices 202, 203, with a diameter of about 10 millimeters are arranged one above the other.
  • Two orifices 204, 205, of smaller diameter, close to 5 millimeters, are arranged on either side of a vertical line A 2 o passing through the centers of orifices 202 and 203.
  • Such an arrangement and such a difference section between the orifices 202 to 205 induce privileged passages of the various components of the contents of the device in these orifices.
  • Liquid components containing fluids and so-called fine particles smaller than 5 millimeters in size and solid components containing particles larger than 5 millimeters are distinguished.
  • the liquid components can borrow all the orifices 202 to 205 whereas the solid components can borrow only the orifices 202 and 203, of larger section.
  • it causes different flows of the components between the rooms C 2 and Cs, depending on whether the components are borrowing one or the other of the orifices 202 to 205. The same applies when the mixture passes from the chamber C 3 to the chamber C 2 through the chamber CB.
  • the arrangement of the orifices 202 to 205 and the different diameters of the orifices 202 to 205 promote the creation of a turbulent flow allowing the homogeneous mixture of the contents of the device 1 during its passage from one chamber C 2 , C 3 to the other through the flange 20.
  • the orifices 202 to 205 of the flange 20 have a mechanical action on the particles, during the passage of the flow between the chambers C 2 and C 8 . This mechanical action reduces the particle size of the original content of the device, such content simulating a food bolus arriving in the stomach.
  • the effective volume of the main chamber Cs is divided into two cavities 80, 81. As seen in Figure 4, the cavities 80, 81 are of different shapes and dimensions.
  • the first cavity 80 is cylindrical with a circular section.
  • the diameter and the position of the cavity 80 are adapted so that it is, on one side, facing all the orifices 202 to 205 of the flange 20 and on the other side facing the compression chamber C 3 according to the embodiment illustrated in FIGS. 7 and 8.
  • the cavity 80 is, on one side, facing the compression chamber C 3 and, on the other side, facing a complementary chamber C 9 , according to the embodiment illustrated in FIGS. 1 to 3.
  • second cavity 81 is configured in L of which a branch 810 is connected to the cavity 80.
  • the section of the branch 810 is such that the components, essentially the liquid components, enter this branch and thus pass from the cavity 80 to a branch 811
  • the other branch 811 of the cavity 81 is closed at its free end 10a, in the normal configuration of use of the device 1.
  • the volume of the cavity 81 is smaller than that of the cavity 80.
  • This second cavity 81 is or facing the openings 202 to 205 of the flange 20 or facing the compression chamber C 3 .
  • Branch 811 defines an isolated storage area temporary content of the device 1, in particular liquid components.
  • the solid components are received, as well as the liquid components, in the cavity 80 during a normal operation cycle of the device.
  • the lower parts of the cavities 81, 80 are respectively connected to outlet orifices 10a, 10b, themselves respectively connected to endpieces 11a, 11b which are closed in the normal configuration of use of the device 1.
  • These tips 1 1a, 11b may be connected to devices for discharging or withdrawing the contents of the device 1. These devices are, for example, peristaltic pumps.
  • the cavity 81 is connected to the tip 11a at the free end of the branch 811.
  • 10a, 10b are normally closed. They are open only when necessary, to draw off one or the other of the cavities 81, 80. Thus, it is possible to selectively withdraw the liquid components from the contents of the device by opening only the orifice 10a.
  • the opening of the orifice 10b allows the withdrawal of the solid and liquid components indifferently. In this way, the gastric emptying of a human being or of monogastric mammals is reproduced in a controlled and more representative way.
  • An output 10c visible in Figure 3, is provided in the vicinity of the orifice
  • the tips 11a, 11b may, in an embodiment not shown, be connected to a device simulating the behavior of the small intestine.
  • a device simulating the behavior of the small intestine.
  • Such a device may comprise, for example, a series of containers reproducing the different parts of the small intestine, namely the duodenum, the jejunum and the ileum.
  • These containers for example of conical shape, are provided with stirring means, heating and pH control.
  • a system of Deoxygenation by injecting nitrogen gas into the containers, is also provided. Pumps connect the containers to each other, the filling taking place in the lower part of the container, the feed in the upper part. Means for selectively introducing products to be tested may be provided on one or more of these containers.
  • the conical shape of the containers makes it possible to optimize mixing, regardless of the volume of the contents present in the containers. These containers are thus cascaded at the outlet of the device 1.
  • a servo container simulating a small intestine and device 1 simulating a stomach In this case, a modification of at least one parameter relating to the operation of a container, among the containers simulating the small intestine, influences the parameters relating to the operation of the other containers. Likewise, a modification of at least one parameter of the device 1 can influence at least one parameter of the small intestine simulation device, and vice versa.
  • this device simulating the behavior of the small intestine may comprise a series of devices 1, adapted.
  • the main block 8 is equipped with a port 12 for introducing the bolus into the chamber C 8 .
  • This bowl is prepared separately and can come from a device simulating gastric filling. Such a device is adapted to optimize the time and the contact surface between the ingredients of the food bolus and the saliva or a solution reproducing it. It is also possible to introduce directly through the orifice 12 the components of the food bolus, namely food and water.
  • products involved in digestion for example, products for the degradation of foods, such as hydrochloric acid, gastric enzymes such as pepsin or lipase or other products involved in the digestive process.
  • Another orifice 16 located in the upper part of the block 8, near the orifice 12, allows the introduction of a probe 160, visible in FIGS. 1 and 7, of pH and / or temperature in the cavity 80 so that to measure and control these parameters during the operating cycle of the device.
  • the measurement of the pressure makes it possible to adapt the movement of the jacks, while avoiding an overpressure in the device 1.
  • the pressure sensor is advantageously connected to an emergency stop member of the jacks.
  • a gas evacuation valve adapted to allow the collection of gas possibly present in the device 1. Such a valve also contributes to maintaining a controlled pressure in the device 1.
  • a complementary chamber C 9 called a pharmaceutical chamber, interposed between the flange 20 and the main block 8, that is to say between the chambers C 2 , C 8 as shown in Figures 1 to 3.
  • the chamber C 9 is formed in a complementary block 9, in this case generally parallelepipedic.
  • the chamber C 9 is cylindrical with circular section and identical to that of the main chamber C 8 .
  • An orifice 18 formed in the upper part of the block 9 is adapted to receive an accessory 17.
  • This accessory removably mounted or not, is adapted to receive test products in order to put them in contact with the contents of the device 1 when passing through the room Cg.
  • the accessory 17 shown in Figure 5 comprises a pierced basket 170, removable, suitable for containing test products in solid form.
  • the shape of the accessory 17, in particular the arrangement, the number and the size of the holes of the basket 170, may be different from that shown in FIG.
  • a cap 19 removably closes the upper part of the basket 170.
  • the accessory 17 is dimensioned such that once positioned in the orifice 18, the plug 19 seals the orifice hermetically.
  • the complementary block 9 is adapted to be easily mounted and removed from the device 1. For this, simply remove the plates 4a, 4b of the chamber C 2 , the sleeve 2, the corresponding rods 5 and the flange 20.
  • the configuration without a chamber Cg, represented in FIGS. 7 and 8 it is not intended to incorporate a product to be tested during the operating cycle of the device other than through the orifice 12, or even through the tubes 13, 14 and 15. The product is then directly incorporated into the content of the device.
  • liquid products they can be introduced into the device, at any time during the operating cycle of the device, through one of the orifices in the main block 8, for example through the orifices 13. , 14, or 15. It is also possible to directly incorporate the liquid product to be tested into the food bowl during the initial filling of the device 1.
  • the accessory 17 comprises a permeable pocket adapted to receive a liquid to be tested. In all cases the accessory 17 is adapted to the product to be tested.
  • the temperature maintenance of the contents of the device is provided by heating films 25 disposed at the sleeves 2, 3 on the outer face thereof.
  • These films are provided with a heating resistive wire.
  • they are transparent, which preserves the vision of the interior of rooms C 2 , C 3 .
  • these films are opaque and adapted to preserve the vision of the interior of the compression chambers, for example by cuts in the film.
  • the main block 8, possibly the flange 20 and / or the complementary block 9 are positioned on a support, for example a heating cradle.
  • such a thermostated support also receives, the sleeves 2, 3. In this case, the use of such a support makes it unnecessary to use the heating films 25.
  • the entire device 1 is housed in a thermostatically controlled enclosure.
  • device 1 Insofar as device 1 is used to simulate physiological or pathological conditions of digestion in a monogastric mammal or in humans, the following parameters are applied to device 1, in an operating mode simulating normal digestion:
  • the temperature of the content is maintained at a value of between 36 and 41 ° C. at least 0.2 ° C.
  • the pH of the contents is regulated between 1 and 8, in particular by introducing hydrochloric acid through one of the tubes 13 to 15.
  • the device 1 is adapted to receive a food bowl, for example, water or mixed food. This introduction is carried out gradually during the cycle or at one time before the beginning of the cycle.
  • the pistons 7 2 , 7 3 are separated from each other as the volume of the contents in the device increases. Conversely, the pistons I 2 , Iz will progressively approach each other as the content decreases, for example during racking, until returning to a predefined position.
  • This variation in the volume of the contents during a cycle of operation depends on the entrances of the alimentary bolus and / or gastric secretions, the residence time of the bolus in the device 1 and racking done.
  • the entries, the residence time and the withdrawal of the content of the device are variable depending on the digestive conditions to reproduce.
  • the instantaneous volume of content present in the device 1 can be up to 600 milliliters.
  • Alternate longitudinal displacements of the two pistons 7 2 , 7 3 are performed during an operating cycle of the device 1.
  • the frequency and the speed of this reciprocating movement of the pistons 7 2 , 7 3 are adjustable.
  • the food bolus is displaced from one compression chamber C 2 or C 3 to the other compression chamber C 3 or C 2 through the main chamber C 8 and the flange 20 and optionally the complementary chamber Cg, located between the chambers C 2 , C 3 .
  • These movements cause a turbulent flow of the contents throughout the device 1, ensuring a homogeneous mixture thereof as well as a grinding that is not aggressive with respect to the solid components. satisfactory and representative way gastric digestion.
  • the mixing and grinding of the gastric contents can be optimized by the presence of several closure plates disposed in the device 1, in particular between the main chamber C 8 and a compression chamber C 2 , C 3 or even between the chambers C 8 and C 9 .
  • the mixing and grinding of the food bolus can be improved by the presence of turbulence pieces or baffles, arranged either in the digestion chamber Cs or at the chambers C 2 , C 3 , or in the orifices 202 to 205 of the flange 20.
  • pistons I 2 , 7 3 to induce movement of the food bolus in the rooms C 2 , C 3 allows a complete, regular and controlled movement of the bowl.
  • the stomach tone is simulated and therefore we reproduce in a representative way what happens during the digestion.
  • the reciprocating movements of the pistons considerably reduce, by a leaching effect, the presence, at the end of the cycle, of undigested residual particles in the chamber Cs whose useful volume is close to 60 milliliters.
  • the device 1 is adapted to study the behavior of a product to be tested, the latter being introduced and / or removed at any time from an operating cycle.
  • a product to be tested may for example be a tablet, a cachet, a capsule, a paste, or even a liquid maintained by a suitable device.
  • the complementary block 9 allows the content of the device to come into contact with the test product previously deposited in the accessory 17, within the intermediate chamber Cg.
  • the device 1 can be followed, on the one hand visually, through the sleeves 2, 3, the evolution of the food bolus, and secondly draw samples of the contents of the device through the orifice 10c.

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Abstract

The invention relates to a device for simulating the stomach of a monogastric mammal or of a human being that includes at least two compression chambers (C2, C3) connected together by an intermediate chamber. Each compression chamber (C2, C3) includes a piston (72, 73) adapted for urging the content of a compression chamber (C2, C3) towards the other compression chamber (C2, C3). The device includes means (20) capable of generating turbulent flow of the device content when passing through the intermediate chamber (C8). The intermediate chamber (C8) is formed in an intermediate block (8) provided with an access means (11a, 12, 16) for supplying products (12) and/or tapping the content of the device at any moment of the operation cycle thereof.

Description

DISPOSITIF DE SIMULATION D'UN ESTOMAC D'UN MAMMIFERE MONOGASTRIQUE OU D'UN ETRE HUMAIN DEVICE FOR SIMULATION OF A STOMACH OF A MONOGASTRIC MAMMAL OR A HUMAN BEING
L'invention a trait à un dispositif de simulation d'un estomac d'un mammifère monogastrique ou d'un être humain.The invention relates to a device for simulating a stomach of a monogastric mammal or a human being.
Un tel dispositif permet d'étudier, in vitro, la digestion des aliments ainsi que le comportement de certains produits ingérés ou susceptibles d'être ingérés, par exemple des compléments alimentaires, des xénobiotiques, des agents pathogènes ou des médicaments. Les études réalisées à l'aide d'un tel dispositif permettent d'apprécier les effets des conditions régnant dans l'estomac sur ces produits, par exemple le temps mis par un composé solide pour être dégradé en particules suffisamment fines pour poursuivre son trajet dans l'intestin, la cinétique de libération de composés actifs, les interactions entre divers produits soumis à l'environnement gastrique, et/ou la survie de microorganismes.Such a device makes it possible to study, in vitro, the digestion of foods as well as the behavior of certain ingested or ingestible products, for example dietary supplements, xenobiotics, pathogens or medicaments. The studies carried out using such a device make it possible to assess the effects of the conditions prevailing in the stomach on these products, for example the time taken by a solid compound to be degraded into sufficiently fine particles to continue its journey through intestine, the kinetics of release of active compounds, the interactions between various products subjected to the gastric environment, and / or the survival of microorganisms.
Un tel dispositif doit, pour être représentatif de l'environnement gastrique, présenter certaines caractéristiques et réaliser plusieurs-fonctions. Le dispositif doit avoir un volume utile adapté pour assurer une simulation efficace des phénomènes de digestion gastrique. Le dispositif doit maintenir le contenu à une température comprise entre 35°C et 45°C, et dont le pH varie entre 1 et 8 environ.Such a device must, to be representative of the gastric environment, have certain characteristics and perform several functions. The device must have a useful volume adapted to ensure efficient simulation of gastric digestion phenomena. The device must maintain the contents at a temperature between 35 ° C and 45 ° C, and whose pH varies between 1 and 8 approximately.
A tout moment du fonctionnement normal du dispositif, on doit pouvoir l'alimenter et y injecter des substances similaires à celles sécrétées par un mammifère monogastrique ou un être humain, au niveau de l'estomac, en réponse à l'ingestion d'un bol alimentaire.At any time during normal operation of the device, it must be able to feed it and inject substances similar to those secreted by a monogastric mammal or a human being, in the stomach, in response to the ingestion of a bowl. food.
Un tel dispositif doit simuler le tonus gastrique, c'est-à-dire assurer un mélange et un broyage non agressif du contenu liquide et/ou solide du dispositif. Il doit également reproduire le transit gastrique. Ce dernier comprend le remplissage du dispositif, avec un contrôle de l'arrivée du bol alimentaire, une période de résidence du bol dans le dispositif et une vidange contrôlée et différenciée du contenu gastrique en direction de l'intestin grêle selon la taille des particules du contenu du dispositif, les composants liquides étant évacués en premier. Par composants liquides, on désigne soit de l'eau, soit des solutions, chargées ou non, la charge des solutions comprenant des particules dites fines, dont le diamètre est inférieur à environ 5 millimètres. De fait, on désigne par composants solides, toute particule d'un diamètre supérieur à environ 5 millimètres. Bien entendu, toutes ces variables sont paramétrables en fonction du mammifère ou de l'être humain simulé et/ou des conditions physiologiques ou pathologiques à reproduire.Such a device must simulate the gastric tone, that is to say ensure mixing and non-aggressive grinding of the liquid and / or solid content of the device. It must also reproduce the gastric transit. The latter comprises the filling of the device, with a control of the arrival of the bolus, a period of residence of the bowl in the device and a controlled and differentiated emptying of the gastric contents towards the small intestine according to the particle size of the content of the device, the liquid components being evacuated first. By liquid components, denotes either water or solutions, charged or not, the charge solutions comprising so-called fine particles, whose diameter is less than about 5 millimeters. In fact, solid components are any particle with a diameter greater than about 5 millimeters. Of course, all these variables can be parameterized according to the mammal or the simulated human being and / or the physiological or pathological conditions to be reproduced.
On connaît par WO-A-94/09895 un dispositif comprenant deux chambres de compression reliées entre elles par une chambre intermédiaire. Ces chambres de compression abritent chacune une poche fermée souple. Un fluide injecté alternativement dans l'une ou l'autre chambre, dans l'espace ménagé entre la paroi interne de la chambre de compression et la paroi externe de la poche souple, permet de comprimer sélectivement les poches. Ces mouvements alternés de compression et de relâchement de chaque poche sont sensés reproduire les contractions stomacales. Or, dans un tel dispositif, la compression et le relâchement des poches n'assurent pas un mélange optimal du bol alimentaire avec les produits simulant les sécrétions gastriques. Des zones mortes existent dans lesquelles il n'y a pas de simulation satisfaisante de la digestion gastrique.WO-A-94/09895 discloses a device comprising two compression chambers interconnected by an intermediate chamber. These compression chambers each house a flexible closed pocket. A fluid injected alternately into one or the other chamber, in the space provided between the inner wall of the compression chamber and the outer wall of the flexible bag, makes it possible to compress the bags selectively. These alternating movements of compression and relaxation of each pocket are supposed to reproduce the stomach contractions. However, in such a device, compression and relaxation of the pockets do not ensure optimal mixing of the food bolus with products simulating gastric secretions. Dead zones exist in which there is no satisfactory simulation of gastric digestion.
De plus, le dispositif décrit dans WO-A-94/09895 ne peut avoir qu'un fonctionnement discontinu, c'est-à-dire que son remplissage initial se fait en une seule fois, en début de cycle. Un tel fonctionnement n'est pas conforme à la réalité physiologique puisque l'arrivée du bol alimentaire dans l'estomac est progressive et dure le temps d'un repas.In addition, the device described in WO-A-94/09895 can only have a discontinuous operation, that is to say that its initial filling is done at once, at the beginning of the cycle. Such a functioning is not in conformity with the physiological reality since the arrival of the alimentary bolus in the stomach is progressive and lasts the time of a meal.
WO-A-2007/010238 décrit un appareil de simulation de la digestion gastrique comprenant deux parties, reproduisant chacune une zone de l'estomac. L'appareil comprend une partie supérieure conique, souple, reliée à une partie inférieure rigide. Cette partie inférieure est formée de deux cylindres concentriques, le cylindre intérieur recevant un piston. Le bol alimentaire passe de la partie supérieure à la partie inférieure par un passage muni d'une valve anti-retour. Le bol alimentaire remplit le volume libéré dans le cylindre intérieur par déplacement du piston. Il y a ensuite un mouvement descendant du cylindre intérieur, simultanément à un mouvement ascendant du piston. Ainsi, le bol alimentaire passe en force, par une ouverture du cylindre intérieur, dans la lumière du cylindre extérieur. Ceci permet un broyage des particules. Si un tel appareil simule la physiologie des différentes parties d'un estomac, il ne permet pas l'introduction de produits et/ou un soutirage sélectif en cours de cycle. De plus, dans la partie supérieure, le mélange du bol alimentaire n'est pas homogène ce qui rend délicat la prise d'un échantillon représentatif du bol et la reproductibilité des expériences. Par ailleurs, lors d'une vidange naturelle de l'estomac, les particules sont évacuées dans l'intestin en fonction de leur granulométrie, ce que ne permettent pas les appareils décrits dans WO-A-94/09895 et WO-A- 2007/010238.WO-A-2007/010238 discloses an apparatus for simulating gastric digestion comprising two parts, each reproducing an area of the stomach. The apparatus comprises a conical, flexible upper portion connected to a rigid lower portion. This lower part is formed of two concentric cylinders, the inner cylinder receiving a piston. The food bowl passes from the top to the bottom by a passage provided with a non-return valve. The food bowl fills the volume released in the inner cylinder by displacement of the piston. Then there is a downward movement of the inner cylinder simultaneously with an upward movement of the piston. Thus, the bolus of food passes in force, by an opening of the inner cylinder, in the light of the outer cylinder. This allows grinding of the particles. If such an apparatus simulates the physiology of the different parts of a stomach, it does not allow the introduction of products and / or a selective withdrawal during the cycle. In addition, in the upper part, the mixture of the bolus is not homogeneous which makes it difficult to take a representative sample of the bowl and the reproducibility of the experiments. Moreover, during a natural emptying of the stomach, the particles are removed in the intestine according to their particle size, which does not allow the apparatus described in WO-A-94/09895 and WO-A-2007 / 010238.
Enfin, les appareils décrits dans WO-A-94/09895 et WO-A- 2007/010238 ne permettent pas de gérer et contrôler facilement l'introduction et/ou l'évacuation de produits, par exemple de produits à tester, à un moment précis de la simulation de la digestion.Finally, the apparatuses described in WO-A-94/09895 and WO-A-2007/010238 do not make it possible to easily manage and control the introduction and / or evacuation of products, for example from products to be tested, to a precise moment of simulation of digestion.
C'est à ces inconvénients qu'entend plus particulièrement remédier l'invention, en proposant un dispositif de simulation d'un estomac sans zone morte, représentatif du fonctionnement global d'un estomac d'un mammifère monogastrique ou d'un être humain qui permet l'introduction de produits et/ou un soutirage contrôlés en cours de digestion et qui assure un mélange homogène du contenu du dispositif.It is to these drawbacks that the invention more particularly intends to remedy, by proposing a device for simulating a stomach without a dead zone, representative of the overall operation of a stomach of a monogastric mammal or of a human being who allows the introduction of controlled products and / or withdrawal during digestion and ensures a homogeneous mixture of the contents of the device.
A cet effet, l'invention a pour objet un dispositif de simulation d'un estomac d'un mammifère monogastrique ou d'un être humain, comprenant au moins deux chambres de compression connectées entre elles par une chambre intermédiaire, caractérisé en ce que chaque chambre de compression comporte un piston adapté pour pousser le contenu d'une chambre de compression en direction de l'autre chambre de compression et en ce qu'il comprend des moyens aptes à provoquer un écoulement turbulent du contenu du dispositif lors de son passage par une chambre intermédiaire ménagée dans un bloc intermédiaire équipé d'au moins un moyen d'accès à la chambre intermédiaire permettant une alimentation en produits et/ou un soutirage du contenu du dispositif à tout moment du cycle de fonctionnement du dispositif. Un tel dispositif permet une agitation et une homogénéisation efficaces du contenu du dispositif simulant un contenu gastrique. Du fait de la présence d'un piston dans chaque chambre de compression, un tel dispositif présente aucune zone morte.For this purpose, the subject of the invention is a device for simulating a stomach of a monogastric mammal or of a human being, comprising at least two compression chambers interconnected by an intermediate chamber, characterized in that each compression chamber comprises a piston adapted to push the contents of a compression chamber towards the other compression chamber and in that it comprises means capable of causing a turbulent flow of the contents of the device during its passage through room intermediate formed in an intermediate block equipped with at least one means of access to the intermediate chamber for a product supply and / or withdrawal of the contents of the device at any time during the operating cycle of the device. Such a device allows effective agitation and homogenization of the contents of the device simulating gastric content. Due to the presence of a piston in each compression chamber, such a device has no dead zone.
Du fait de la présence de moyens d'accès à la chambre intermédiaire, on réalise une alimentation et/ou un soutirage du dispositif de manière progressive et indépendante.Due to the presence of access means to the intermediate chamber, a supply and / or withdrawal of the device is carried out gradually and independently.
Selon des aspects avantageux mais non obligatoires de l'invention, le dispositif peut incorporer une ou plusieurs des caractéristiques suivantes :According to advantageous but not obligatory aspects of the invention, the device may incorporate one or more of the following features:
- Chaque piston est mobile selon une direction parallèle à un axe longitudinal commun aux deux chambres de compression et forme un fond mobile à chaque chambre.- Each piston is movable in a direction parallel to a longitudinal axis common to the two compression chambers and forms a movable bottom to each chamber.
- La chambre intermédiaire comprend deux cavités de forme et de dimensions différentes.- The intermediate chamber comprises two cavities of different shapes and sizes.
- Une première cavité est cylindrique à section circulaire et une seconde cavité est configurée en L dont une branche est reliée à la première cavité et dont l'autre branche est non débouchante dans les chambres de compression, en fonctionnement normal du dispositif.- A first cavity is cylindrical with circular section and a second cavity is configured in L, a branch is connected to the first cavity and the other branch is non-emerging in the compression chambers, in normal operation of the device.
- Les moyens aptes à provoquer l'écoulement turbulent comprennent au moins une flasque d'obturation montée entre une extrémité d'une chambre de compression et une extrémité de la chambre intermédiaire.- The means capable of causing the turbulent flow comprise at least one sealing flange mounted between one end of a compression chamber and one end of the intermediate chamber.
- Cette flasque est pourvue d'au moins un orifice calibré de passage du contenu du dispositif, d'une chambre de compression à la chambre intermédiaire et réciproquement.- This flange is provided with at least one calibrated orifice for passing the contents of the device, a compression chamber to the intermediate chamber and vice versa.
- La flasque d'obturation est disposée de manière que son ou ses orifices soient en regard d'une cavité cylindrique de la chambre intermédiaire. - Le bloc intermédiaire comprend un orifice d'accès permettant l'introduction d'une sonde de pH et/ou de température dans la chambre intermédiaire.- The sealing flange is arranged so that its orifices are facing a cylindrical cavity of the intermediate chamber. - The intermediate block comprises an access port for the introduction of a pH probe and / or temperature in the intermediate chamber.
- Le bloc intermédiaire comprend un orifice d'accès permettant l'introduction d'un capteur de pression dans la chambre intermédiaire.- The intermediate block comprises an access port for the introduction of a pressure sensor into the intermediate chamber.
- Un bloc complémentaire délimitant une chambre complémentaire, apte à recevoir un produit à tester dans le dispositif, est intercalé entre la flasque d'obturation et le bloc intermédiaire.- A complementary block defining a complementary chamber, adapted to receive a product to be tested in the device, is interposed between the sealing flange and the intermediate block.
- Le bloc complémentaire délimitant la chambre complémentaire est intercalé de manière amovible entre la flasque et le bloc intermédiaire.- The complementary block defining the complementary chamber is interposed removably between the flange and the intermediate block.
- Le bloc complémentaire comprend un orifice propre à recevoir un accessoire destiné à contenir un produit à tester.- The complementary block comprises an orifice adapted to receive an accessory for containing a product to be tested.
L'invention sera mieux comprise et d'autres avantages de celle-ci apparaîtront plus clairement à la lecture de la description qui va suivre de deux modes de réalisation d'un dispositif conforme à l'invention, donnée uniquement à titre d'exemple et faite en se référant aux dessins annexés dans lesquels :The invention will be better understood and other advantages thereof will appear more clearly on reading the following description of two embodiments of a device according to the invention, given solely by way of example and made with reference to the accompanying drawings in which:
- la figure 1 est une vue en perspective, simplifiée, d'un premier mode de réalisation d'un dispositif conforme à l'invention équipé d'un bloc complémentaire,FIG. 1 is a simplified perspective view of a first embodiment of a device according to the invention equipped with a complementary block,
- les figures 2 et 3 sont des coupes longitudinales du dispositif de la figure 1 respectivement dans le sens des flèches H-Il et Ill-lll,FIGS. 2 and 3 are longitudinal sections of the device of FIG. 1 respectively in the direction of the arrows H-II and III-III,
- la figure 4 est une coupe selon la ligne IV-IV à la figure 2, - la figure 5 est une vue en perspective, à plus grande échelle, d'un accessoire, destiné à contenir un produit, dans le dispositif des figures 1 à 3,FIG. 4 is a section along the line IV-IV in FIG. 2; FIG. 5 is a perspective view, on a larger scale, of an accessory intended to contain a product, in the device of FIGS. at 3,
- la figure 6 est une vue de face, à une plus grande échelle que les figures 1 à 3, d'une flasque d'obturation située entre une chambre de compression et un bloc complémentaire du dispositif représenté aux figures 1 à 3,FIG. 6 is a front view, on a larger scale than FIGS. 1 to 3, of a closure flange situated between a compression chamber and a complementary block of the device represented in FIGS. 1 to 3,
- la figure 7 est une vue similaire à la figure 1 , d'un deuxième mode de réalisation du dispositif, celui-ci n'étant pas équipé d'un bloc complémentaire et - la figure 8 est une coupe longitudinale du dispositif de la figure 7 selon les flèches VIII-VIII.FIG. 7 is a view similar to FIG. 1, of a second embodiment of the device, the latter not being equipped with a complementary block and - Figure 8 is a longitudinal section of the device of Figure 7 according to the arrows VIII-VIII.
Le dispositif 1 , représenté aux figures 1 , 2, 3, 7 et 8, comprend deux chambres de compression C2, C3. Ces chambres sont délimitées par des manchons 2 et 3 tubulaires à section cylindrique et, avantageusement sur au moins une partie, réalisés en un matériau transparent, chimiquement et biologiquement neutre et aisément stérilisable, par exemple en verre ou en polymèthacrylate. Un tel matériau transparent permet une surveillance visuelle du contenu des chambres C2 et C3.The device 1, shown in FIGS. 1, 2, 3, 7 and 8, comprises two compression chambers C 2 , C 3 . These chambers are delimited by cylindrical sleeve 2 and 3 tubular cylindrical and, preferably on at least a portion, made of a transparent material, chemically and biologically neutral and easily sterilizable, for example glass or polymethacrylate. Such a transparent material makes it possible to visually monitor the contents of chambers C 2 and C 3 .
Les manchons 2 et 3 sont insérés dans des orifices de forme correspondante ménagés dans des plaques carrées 4a, 4b, 4ç, 4d. Dans le mode de réalisation illustré à la figure 7, des tiges 5 relient les angles des plaques 4 à un bloc intermédiaire 8, dit bloc principal, de forme globalement cubique et qui délimite une chambre intermédiaire C8, dite chambre principale. Les plaques 4a à 4d et les tiges 5 forment ainsi un bâti de maintien et de protection des manchons 2, 3.The sleeves 2 and 3 are inserted into correspondingly shaped orifices formed in square plates 4a, 4b, 4c, 4d. In the embodiment illustrated in FIG. 7, rods 5 connect the angles of the plates 4 to an intermediate block 8, called the main block, of generally cubic shape and which delimits an intermediate chamber C 8 , called the main chamber. The plates 4a to 4d and the rods 5 thus form a frame for holding and protecting the sleeves 2, 3.
A chaque extrémité 40, 41 du bâti, une plaque d'extrémité 4a, 4d, respectivement est pourvue d'un orifice central permettant le passage d'un vérin 62, 63. Le passage de chaque vérin 62, 63 s'effectue de manière étanche, l'intérieur des chambres C2, C3 restant isolé de l'extérieur. Les vérins 62, 63 sont avantageusement de type hydraulique ou électrique.At each end 40, 41 of the frame, an end plate 4a, 4d, respectively, is provided with a central orifice allowing the passage of a cylinder 6 2 , 63. The passage of each cylinder 6 2 , 63 is carried out in a sealed manner, the inside of the chambers C 2 , C 3 remaining isolated from the outside. The cylinders 6 2 , 6 3 are advantageously hydraulic or electric type.
Chaque vérin 62, 63 déplace respectivement un piston 72, 73. Chaque piston est mobile selon une direction parallèle à un axe longitudinal A-A' commun aux chambres C2, C3. Chaque piston 72, 73 forme une extrémité ou fond mobile 72, 73 de la chambre C2, C3 dans laquelle il est installé. Les plaques 4a à 4d, les pistons 72, 73 et les vérins 62, 63 ainsi qu'avantageusement d'autres pièces constitutives du dispositif 1 , sont réalisés dans un matériau rigide, chimiquement et biologiquement neutre et aisément stérilisable.Each cylinder 6 2 , 6 3 respectively moves a piston 7 2 , 7 3 . Each piston is movable in a direction parallel to a longitudinal axis AA 'common to the chambers C 2 , C 3 . Each piston 7 2 , 7 3 forms an end or movable bottom 7 2 , 7 3 of the chamber C 2 , C 3 in which it is installed. The plates 4a to 4d, the pistons 7 2 , 73 and the cylinders 6 2 , 6 3 and advantageously other component parts of the device 1, are made of a rigid material, chemically and biologically neutral and easily sterilizable.
La course de chaque piston 72, 73 est adaptée pour que celui-ci se déplace, dans chaque chambre C2, C3, respectivement d'une extrémité 21 , 31 de la chambre C2, C3 proche d'une plaque 4a, 4d en direction de l'autre extrémité respectivement 22, 32 proche du bloc 8, et inversement.The stroke of each piston 7 2 , 7 3 is adapted so that it moves, in each chamber C 2 , C 3 , respectively of an end 21, 31 of the chamber C 2 , C 3 close to a plate 4a, 4d towards the other end respectively 22, 32 near the block 8, and vice versa.
La course de chaque piston 72l 73 s'effectue en préservant l'étanchéité dans chaque chambre de compression C2, C3. Dans un mode de réalisation non illustré, chaque piston 72, 73 peut se déplacer indépendamment de l'autre à une vitesse et une fréquence réglables.The stroke of each piston 7 2l 7 3 is effected while preserving the tightness in each compression chamber C 2 , C 3 . In an embodiment not illustrated, each piston 7 2 , 7 3 can move independently of the other at an adjustable speed and frequency.
Les chambres de compression C2, C3 sont reliées au niveau de leurs extrémités 22 et 32 à la chambre principale Cs- Dans le mode de réalisation illustré aux figures 7 et 8, l'extrémité 22 de la chambre C2 est adaptée pour assurer le passage du contenu de la chambre C2 à la chambre principale C8.The compression chambers C 2 , C 3 are connected at their ends 22 and 32 to the main chamber Cs. In the embodiment illustrated in FIGS. 7 and 8, the end 22 of the chamber C 2 is adapted to ensure the passage of the contents of the chamber C 2 to the main chamber C 8 .
Cette extrémité 22 est délimitée par une plaque ou flasque d'obturationThis end 22 is delimited by a plate or flange closure
20. Cette flasque 20, représentée en vue de face à la figure 6, reçoit l'extrémité du manchon 2 dans une rainure circulaire 201. Lorsqu'il est en fin de course, le piston 72 est en appui sur la flasque 20. La flasque d'obturation 20 comprend quatre orifices traversants et circulaires, 202, 203, 204, 205, qui permettent le passage du contenu de la chambre C2 en direction de, ou venant de, la chambre principale C8. En variante, le nombre des orifices traversants de la flasque 20 est différent de quatre, en étant supérieur ou égal à un.20. This flange 20, shown in front view of FIG. 6, receives the end of the sleeve 2 in a circular groove 201. When it is at the end of the stroke, the piston 7 2 bears on the flange 20. The closure flange 20 comprises four through-holes and circular, 202, 203, 204, 205, which allow the passage of the contents of the chamber C 2 towards or from the main chamber C 8 . Alternatively, the number of through holes of the flange 20 is different from four, being greater than or equal to one.
Les orifices 202 à 205 sont disposés au voisinage d'un bord de la flasque 20. Deux orifices 202, 203, d'un diamètre voisin de 10 millimètres sont disposés l'un au dessus de l'autre. Deux orifices 204, 205, d'un diamètre plus faible, voisin de 5 millimètres sont disposés de part et d'autre d'une droite A2o verticale passant par les centres des orifices 202 et 203. Une telle disposition et une telle différence de section entre les orifices 202 à 205 induisent des passages privilégiés des différents composants du contenu du dispositif dans ces orifices.The orifices 202 to 205 are arranged in the vicinity of an edge of the flange 20. Two orifices 202, 203, with a diameter of about 10 millimeters are arranged one above the other. Two orifices 204, 205, of smaller diameter, close to 5 millimeters, are arranged on either side of a vertical line A 2 o passing through the centers of orifices 202 and 203. Such an arrangement and such a difference section between the orifices 202 to 205 induce privileged passages of the various components of the contents of the device in these orifices.
On distingue des composants liquides contenant des fluides et des particules dites fines dont la taille est inférieure à 5 millimètres et des composants solides contenant des particules d'une taille supérieure à 5 millimètres. Les composants liquides peuvent emprunter tous les orifices 202 à 205 alors que les composants solides ne peuvent emprunter que les orifices 202 et 203, de plus grande section. Ainsi, on provoque des flux différents des composants entre les chambres C2 et Cs, selon que les composants empruntent l'un ou l'autre des orifices 202 à 205. Il en va de même lorsque le mélange passe de la chambre C3 vers la chambre C2 à travers la chambre CB. La disposition des orifices 202 à 205 et les diamètres différents des orifices 202 à 205 favorisent la création d'un écoulement turbulent permettant le mélange homogène du contenu du dispositif 1 lors de son passage d'une chambre C2, C3 à l'autre à travers la flasque 20. De plus, les orifices 202 à 205 de la flasque 20 ont une action mécanique sur les particules, lors du passage du flux entre les chambres C2 et C8. Cette action mécanique permet de réduire la taille des particules du contenu initial du dispositif, un tel contenu simulant un bol alimentaire arrivant dans l'estomac.Liquid components containing fluids and so-called fine particles smaller than 5 millimeters in size and solid components containing particles larger than 5 millimeters are distinguished. The liquid components can borrow all the orifices 202 to 205 whereas the solid components can borrow only the orifices 202 and 203, of larger section. Thus, it causes different flows of the components between the rooms C 2 and Cs, depending on whether the components are borrowing one or the other of the orifices 202 to 205. The same applies when the mixture passes from the chamber C 3 to the chamber C 2 through the chamber CB. The arrangement of the orifices 202 to 205 and the different diameters of the orifices 202 to 205 promote the creation of a turbulent flow allowing the homogeneous mixture of the contents of the device 1 during its passage from one chamber C 2 , C 3 to the other through the flange 20. In addition, the orifices 202 to 205 of the flange 20 have a mechanical action on the particles, during the passage of the flow between the chambers C 2 and C 8 . This mechanical action reduces the particle size of the original content of the device, such content simulating a food bolus arriving in the stomach.
Le volume utile de la chambre principale Cs est divisé en deux cavités 80, 81. Comme visible à la figure 4, les cavités 80, 81 sont de formes et de dimensions différentes.The effective volume of the main chamber Cs is divided into two cavities 80, 81. As seen in Figure 4, the cavities 80, 81 are of different shapes and dimensions.
La première cavité 80 est cylindrique à section circulaire. Le diamètre et la position de la cavité 80 sont adaptés pour qu'elle soit, d'un coté, en regard de tous les orifices 202 à 205 de la flasque 20 et de l'autre coté en regard de la chambre de compression C3, selon le mode de réalisation illustré aux figures 7 et 8.The first cavity 80 is cylindrical with a circular section. The diameter and the position of the cavity 80 are adapted so that it is, on one side, facing all the orifices 202 to 205 of the flange 20 and on the other side facing the compression chamber C 3 according to the embodiment illustrated in FIGS. 7 and 8.
La cavité 80 est, d'un côté, en regard de la chambre de compression C3 et, de l'autre côté, en regard d'une chambre complémentaire C9, selon le mode de réalisation illustré aux figures 1 à 3. La seconde cavité 81 est configurée en L dont une branche 810 est reliée à la cavité 80. La section de la branche 810 est telle que les composants, essentiellement les composants liquides, pénètrent dans cette branche et ainsi passent de la cavité 80 vers une branche 811. L'autre branche 811 de la cavité 81 est fermée à son extrémité libre 10a, en configuration normale d'utilisation du dispositif 1. Le volume de la cavité 81 est inférieur à celui de la cavité 80. Cette seconde cavité 81 n'est ni en regard des orifices 202 à 205 de la flasque 20 ni en regard de la chambre de compression C3. La branche 811 définit donc une zone isolée de stockage temporaire du contenu du dispositif 1 , en particulier des composants liquides. Les composants solides sont reçus, de même que les composants liquides, dans la cavité 80 lors d'un cycle de fonctionnement normal du dispositif. Comme représenté à la figure 4, les parties basses des cavités 81, 80 sont reliées respectivement à des orifices de sortie 10a, 10b, eux-mêmes respectivement connectés à des embouts 11 a, 11 b qui sont fermés en configuration normale d'utilisation du dispositif 1. Ces embouts 1 1a, 11b peuvent être reliés à des dispositifs d'évacuation ou de soutirage du contenu du dispositif 1. Ces dispositifs sont, par exemple, des pompes péristaltiques.The cavity 80 is, on one side, facing the compression chamber C 3 and, on the other side, facing a complementary chamber C 9 , according to the embodiment illustrated in FIGS. 1 to 3. second cavity 81 is configured in L of which a branch 810 is connected to the cavity 80. The section of the branch 810 is such that the components, essentially the liquid components, enter this branch and thus pass from the cavity 80 to a branch 811 The other branch 811 of the cavity 81 is closed at its free end 10a, in the normal configuration of use of the device 1. The volume of the cavity 81 is smaller than that of the cavity 80. This second cavity 81 is or facing the openings 202 to 205 of the flange 20 or facing the compression chamber C 3 . Branch 811 defines an isolated storage area temporary content of the device 1, in particular liquid components. The solid components are received, as well as the liquid components, in the cavity 80 during a normal operation cycle of the device. As shown in FIG. 4, the lower parts of the cavities 81, 80 are respectively connected to outlet orifices 10a, 10b, themselves respectively connected to endpieces 11a, 11b which are closed in the normal configuration of use of the device 1. These tips 1 1a, 11b may be connected to devices for discharging or withdrawing the contents of the device 1. These devices are, for example, peristaltic pumps.
La cavité 81 est reliée à l'embout 11a au niveau de l'extrémité libre de la branche 811. Lors d'un cycle de simulation de la digestion, les orificesThe cavity 81 is connected to the tip 11a at the free end of the branch 811. During a simulation cycle of the digestion, the orifices
10a, 10b sont normalement fermés. Ils ne sont ouverts qu'en cas de besoin, pour effectuer des soutirages de l'une ou l'autre des cavités 81 , 80. Ainsi, il est possible de soutirer sélectivement les composants liquides du contenu du dispositif en ouvrant uniquement l'orifice 10a. L'ouverture de l'orifice 10b permet le soutirage des composants solides et liquides indifféremment. De cette manière, on reproduit de façon contrôlée et plus représentative la vidange gastrique d'un être humain ou de mammifères monogastriques. Une sortie 10ç, visible à la figure 3, est prévue au voisinage de l'orifice10a, 10b are normally closed. They are open only when necessary, to draw off one or the other of the cavities 81, 80. Thus, it is possible to selectively withdraw the liquid components from the contents of the device by opening only the orifice 10a. The opening of the orifice 10b allows the withdrawal of the solid and liquid components indifferently. In this way, the gastric emptying of a human being or of monogastric mammals is reproduced in a controlled and more representative way. An output 10c, visible in Figure 3, is provided in the vicinity of the orifice
10b. Cette sortie 10ç débouche en partie basse de la cavité 80. Elle est fermée en configuration normale d'utilisation. La sortie 10ç permet une prise d'échantillons du contenu du dispositif. En cas de besoin, cette sortie 10ç permet également une vidange totale et rapide du dispositif 1. Les embouts 11a, 11 b peuvent, dans un mode de réalisation non représenté, être reliés à un dispositif simulant le comportement de l'intestin grêle. Un tel dispositif peut comprendre, par exemple, une série de récipients reproduisant les différentes parties de l'intestin grêle, à savoir le duodénum, le jéjunum et l'iléon. Ces récipients, par exemple de forme conique, sont pourvus de moyens d'agitation, de chauffage et de contrôle du pH. Ils sont également équipés de moyens d'introduction contrôlée de produits tels que des solutions reproduisant des sécrétions pancréatiques et biliaires, de l'eau, du bicarbonate de sodium ou autres. Un système de désoxygénation, par injection d'azote gazeux dans les récipients, est également prévu. Des pompes relient les récipients entre eux, le soutirage s'effectuant en partie basse du récipient, l'alimentation en partie haute. Des moyens d'introduction sélective de produits à tester peuvent être prévus sur un ou plusieurs de ces récipients. La forme conique des récipients permet d'optimiser le mélange, quel que soit le volume du contenu présent dans les récipients. Ces récipients sont ainsi disposés en cascade à la sortie du dispositif 1.10b. This output 10c opens at the bottom of the cavity 80. It is closed in normal configuration of use. The output 10c allows a sampling of the contents of the device. If necessary, this output 10c also allows a complete and rapid emptying of the device 1. The tips 11a, 11b may, in an embodiment not shown, be connected to a device simulating the behavior of the small intestine. Such a device may comprise, for example, a series of containers reproducing the different parts of the small intestine, namely the duodenum, the jejunum and the ileum. These containers, for example of conical shape, are provided with stirring means, heating and pH control. They are also equipped with means of controlled introduction of products such as solutions reproducing pancreatic and biliary secretions, water, sodium bicarbonate or others. A system of Deoxygenation, by injecting nitrogen gas into the containers, is also provided. Pumps connect the containers to each other, the filling taking place in the lower part of the container, the feed in the upper part. Means for selectively introducing products to be tested may be provided on one or more of these containers. The conical shape of the containers makes it possible to optimize mixing, regardless of the volume of the contents present in the containers. These containers are thus cascaded at the outlet of the device 1.
Il est possible de prévoir un asservissement des récipients simulant un intestin grêle et du dispositif 1 simulant un estomac. Dans ce cas, une modification d'au moins un paramètre relatif au fonctionnement d'un récipient, parmi les récipients simulant l'intestin grêle, influence les paramètres relatifs au fonctionnement des autres récipients. De même, une modification d'au moins un paramètre du dispositif 1 , peut influencer au moins un paramètre du dispositif de simulation de l'intestin grêle, et réciproquement.It is possible to provide a servo container simulating a small intestine and device 1 simulating a stomach. In this case, a modification of at least one parameter relating to the operation of a container, among the containers simulating the small intestine, influences the parameters relating to the operation of the other containers. Likewise, a modification of at least one parameter of the device 1 can influence at least one parameter of the small intestine simulation device, and vice versa.
En variante, ce dispositif simulant le comportement de l'intestin grêle peut comprendre une série de dispositifs 1 , adaptés.Alternatively, this device simulating the behavior of the small intestine may comprise a series of devices 1, adapted.
En partie supérieure, le bloc principal 8 est équipé d'un orifice 12 d'introduction du bol alimentaire dans la chambre C8. Ce bol est préparé séparément et il peut provenir d'un dispositif simulant le remplissage gastrique. Un tel dispositif est adapté pour optimiser le temps et la surface de contact entre les ingrédients du bol alimentaire et la salive ou une solution la reproduisant. On peut également introduire directement par l'orifice 12 les composants du bol alimentaire, à savoir des aliments, de l'eau.In the upper part, the main block 8 is equipped with a port 12 for introducing the bolus into the chamber C 8 . This bowl is prepared separately and can come from a device simulating gastric filling. Such a device is adapted to optimize the time and the contact surface between the ingredients of the food bolus and the saliva or a solution reproducing it. It is also possible to introduce directly through the orifice 12 the components of the food bolus, namely food and water.
Des tubulures 13, 14 et 15 montées sur le bloc 8, débouchent latéralement, en partie haute de la chambre C8, au niveau de la cavité 80. Elles permettent l'injection, en quantité désirée et à n'importe quel moment du cycle de simulation de la digestion, de produits intervenant dans la digestion, par exemple, des produits permettant la dégradation des aliments, tels que de l'acide chlorhydrique, des enzymes gastriques comme la pepsine ou la lipase ou d'autres produits intervenant dans le processus de digestion.Tubes 13, 14 and 15 mounted on the block 8, open laterally, in the upper part of the chamber C 8 , at the cavity 80. They allow the injection, in desired quantity and at any time of the cycle simulation of digestion, products involved in digestion, for example, products for the degradation of foods, such as hydrochloric acid, gastric enzymes such as pepsin or lipase or other products involved in the digestive process.
Un autre orifice 16, situé en partie haute du bloc 8, à proximité de l'orifice 12, permet l'introduction d'une sonde 160, visible aux figures 1 et 7, de pH et/ou de température dans la cavité 80 afin de mesurer et contrôler ces paramètres au cours du cycle de fonctionnement du dispositif.Another orifice 16, located in the upper part of the block 8, near the orifice 12, allows the introduction of a probe 160, visible in FIGS. 1 and 7, of pH and / or temperature in the cavity 80 so that to measure and control these parameters during the operating cycle of the device.
Un autre orifice 16a situé sur le bloc 8, au niveau de la branche 811 et visible à la figure 4, permet l'introduction d'un capteur de pression, non représenté, qui mesure et contrôle la pression dans le dispositif 1 au cours du cycle de digestion. La mesure de la pression permet d'adapter le mouvement des vérins, tout en évitant une surpression dans le dispositif 1. Pour cela, le capteur de pression est avantageusement relié à un organe d'arrêt d'urgence des vérins.Another orifice 16a situated on the block 8, at the level of the branch 811 and visible in FIG. 4, allows the introduction of a pressure sensor, not shown, which measures and controls the pressure in the device 1 during the digestion cycle. The measurement of the pressure makes it possible to adapt the movement of the jacks, while avoiding an overpressure in the device 1. For this, the pressure sensor is advantageously connected to an emergency stop member of the jacks.
D'autres orifices peuvent être prévus sur le bloc 8 ou sur des blocs intermédiaires disposés entre le bloc 8 et une chambre de compression C2, C3 afin de permettre si besoin la mise en place d'autres capteurs. Il est également possible d'équiper le bloc 8 d'une soupape d'évacuation des gaz adaptée pour permettre le prélèvement de gaz présent éventuellement dans le dispositif 1. Une telle soupape participe également au maintien d'une pression contrôlée dans le dispositif 1.Other orifices may be provided on the block 8 or on intermediate blocks arranged between the block 8 and a compression chamber C 2 , C 3 in order to allow, if necessary, the introduction of other sensors. It is also possible to equip the block 8 with a gas evacuation valve adapted to allow the collection of gas possibly present in the device 1. Such a valve also contributes to maintaining a controlled pressure in the device 1.
Lorsqu'on souhaite introduire dans le dispositif 1 des produits à tester, on utilise une chambre complémentaire C9 dite chambre pharmaceutique, intercalée entre la flasque 20 et le bloc principal 8, c'est-à-dire entre les chambres C2, C8 comme représenté aux figures 1 à 3. La chambre C9 est ménagée dans un bloc complémentaire 9, en l'espèce globalement parallélépipédique. La chambre C9 est cylindrique à section circulaire et identique à celle de la chambre principale C8. Une telle configuration permet un libre passage du contenu du dispositif entre ces deux chambres C8 et C9. Un orifice 18 ménagé en partie supérieure du bloc 9 est adapté pour recevoir un accessoire 17. Cet accessoire, monté de manière amovible ou non, est adapté pour recevoir des produits à tester afin de mettre ceux-ci en contact avec le contenu du dispositif 1 lors de son passage par la chambre Cg. L'accessoire 17 représenté à la figure 5, comprend un panier percé 170, amovible, propre à contenir des produits à tester sous forme solide.When it is desired to introduce into the device 1 the products to be tested, there is used a complementary chamber C 9 called a pharmaceutical chamber, interposed between the flange 20 and the main block 8, that is to say between the chambers C 2 , C 8 as shown in Figures 1 to 3. The chamber C 9 is formed in a complementary block 9, in this case generally parallelepipedic. The chamber C 9 is cylindrical with circular section and identical to that of the main chamber C 8 . Such a configuration allows free passage of the contents of the device between these two chambers C 8 and C 9 . An orifice 18 formed in the upper part of the block 9 is adapted to receive an accessory 17. This accessory, removably mounted or not, is adapted to receive test products in order to put them in contact with the contents of the device 1 when passing through the room Cg. The accessory 17 shown in Figure 5, comprises a pierced basket 170, removable, suitable for containing test products in solid form.
La forme de l'accessoire 17, en particulier la disposition, le nombre et la taille des trous du panier 170, peut être différente de celle représentée à la figure 5.The shape of the accessory 17, in particular the arrangement, the number and the size of the holes of the basket 170, may be different from that shown in FIG.
Un bouchon 19 obture, de manière amovible, la partie supérieure du panier 170. L'accessoire 17 est dimensionné de telle sorte qu'une fois positionné dans l'orifice 18, le bouchon 19 obture hermétiquement l'orificeA cap 19 removably closes the upper part of the basket 170. The accessory 17 is dimensioned such that once positioned in the orifice 18, the plug 19 seals the orifice hermetically.
18. Seul le panier 170 plonge dans la chambre Cg, mettant ainsi en contact le produit à tester avec le contenu du dispositif 1.18. Only the basket 170 dives into the chamber Cg, thus putting the product under test into contact with the contents of the device 1.
Le bloc complémentaire 9 est adapté pour être monté et démonté aisément du dispositif 1. Pour cela, il suffit de démonter les plaques 4a, 4b de la chambre C2, le manchon 2, les tiges 5 correspondantes et la flasque 20. Dans la configuration sans chambre Cg, représentée aux figures 7 et 8, il n'est pas prévu d'incorporer un produit à tester en cours de cycle de fonctionnement du dispositif autrement que par l'orifice 12, voire par les tubulures 13, 14 et 15. Le produit est alors directement incorporé au contenu du dispositif. Bien entendu, il est possible d'effectuer des cycles de simulation de la digestion en présence du bloc 9 et de l'accessoire 17 dans le dispositif 1 sans introduire de produit à tester dans l'accessoire 17.The complementary block 9 is adapted to be easily mounted and removed from the device 1. For this, simply remove the plates 4a, 4b of the chamber C 2 , the sleeve 2, the corresponding rods 5 and the flange 20. In the configuration without a chamber Cg, represented in FIGS. 7 and 8, it is not intended to incorporate a product to be tested during the operating cycle of the device other than through the orifice 12, or even through the tubes 13, 14 and 15. The product is then directly incorporated into the content of the device. Of course, it is possible to perform digestion simulation cycles in the presence of the block 9 and the accessory 17 in the device 1 without introducing test product in the accessory 17.
Dans le cas où l'on souhaite tester des produits liquides, ceux-ci peuvent être introduits dans le dispositif, à tout moment du cycle de fonctionnement du dispositif, par un des orifices ménagés dans le bloc principal 8, par exemple par les orifices 13, 14, ou 15. Il est également possible d'incorporer directement le produit liquide à tester dans le bol alimentaire lors du remplissage initial du dispositif 1.In the case where it is desired to test liquid products, they can be introduced into the device, at any time during the operating cycle of the device, through one of the orifices in the main block 8, for example through the orifices 13. , 14, or 15. It is also possible to directly incorporate the liquid product to be tested into the food bowl during the initial filling of the device 1.
Dans un autre mode de réalisation non illustré, l'accessoire 17 comprend une poche perméable propre à recevoir un liquide à tester. Dans tous les cas l'accessoire 17 est adapté au produit à tester.In another embodiment not illustrated, the accessory 17 comprises a permeable pocket adapted to receive a liquid to be tested. In all cases the accessory 17 is adapted to the product to be tested.
Le maintien en température du contenu du dispositif est assuré par des films chauffants 25 disposés au niveau des manchons 2, 3 sur la face extérieure de ces derniers. Ces films sont pourvus d'un fil résistif chauffant. Dans le mode de réalisation représenté, ils sont transparents, ce qui préserve la vision de l'intérieur des chambres C2, C3. En variante, ces films sont opaques et adaptés pour préserver la vision de l'intérieur des chambres de compression, par exemple par des découpes ménagées dans le film. Dans un mode de réalisation non illustré, le bloc principal 8, éventuellement la flasque 20 et/ou le bloc complémentaire 9 sont positionnés sur un support, par exemple un berceau chauffant.The temperature maintenance of the contents of the device is provided by heating films 25 disposed at the sleeves 2, 3 on the outer face thereof. These films are provided with a heating resistive wire. In the embodiment shown, they are transparent, which preserves the vision of the interior of rooms C 2 , C 3 . Alternatively, these films are opaque and adapted to preserve the vision of the interior of the compression chambers, for example by cuts in the film. In a non-illustrated embodiment, the main block 8, possibly the flange 20 and / or the complementary block 9 are positioned on a support, for example a heating cradle.
Dans un autre mode de réalisation non illustré, un tel support thermostaté reçoit également, les manchons 2, 3. Dans ce cas, l'utilisation d'un tel support rend inutile l'utilisation des films chauffants 25.In another embodiment not illustrated, such a thermostated support also receives, the sleeves 2, 3. In this case, the use of such a support makes it unnecessary to use the heating films 25.
En variante, tout le dispositif 1 est logé dans une enceinte thermostatée.In a variant, the entire device 1 is housed in a thermostatically controlled enclosure.
Dans la mesure où le dispositif 1 est utilisé pour simuler des conditions physiologiques ou pathologiques de la digestion chez un mammifère monogastrique ou chez l'être humain, les paramètres suivants sont appliqués au dispositif 1 , dans un mode de fonctionnement simulant une digestion normale :Insofar as device 1 is used to simulate physiological or pathological conditions of digestion in a monogastric mammal or in humans, the following parameters are applied to device 1, in an operating mode simulating normal digestion:
La température du contenu est maintenue à une valeur comprise entre 36 et 410C à au moins 0,20C près. Le pH du contenu est régulé entre 1 et 8, notamment par l'introduction d'acide chlorhydrique par l'une des tubulures 13 à 15.The temperature of the content is maintained at a value of between 36 and 41 ° C. at least 0.2 ° C. The pH of the contents is regulated between 1 and 8, in particular by introducing hydrochloric acid through one of the tubes 13 to 15.
Le dispositif 1 est adapté pour recevoir un bol alimentaire, par exemple, de l'eau ou des aliments mixés. Cette introduction s'effectue de manière progressive en cours de cycle ou en une seule fois avant le début du cycle.The device 1 is adapted to receive a food bowl, for example, water or mixed food. This introduction is carried out gradually during the cycle or at one time before the beginning of the cycle.
Pour introduire un bol alimentaire dans le dispositif, on écarte, si besoin, les pistons 72, 73 l'un de l'autre à mesure de l'augmentation du volume du contenu dans le dispositif. Inversement, les pistons I2, Iz vont progressivement se rapprocher l'un de l'autre à mesure de la diminution du contenu, par exemple lors d'un soutirage, jusqu'à revenir à une position prédéfinie. Cette variation du volume du contenu au cours d'un cycle de fonctionnement dépend des entrées de bol alimentaire et/ou de sécrétions gastriques, des temps de résidence du bol alimentaire dans le dispositif 1 et des soutirages réalisés. Les entrées, le temps de résidence et les soutirages du contenu du dispositif sont variables en fonction des conditions digestives à reproduire. Le volume instantané de contenu présent dans le dispositif 1 peut aller jusqu'à 600 millilitres. Des déplacements longitudinaux alternatifs des deux pistons 72, 73 sont réalisés lors d'un cycle de fonctionnement du dispositif 1. La fréquence et la vitesse de ce mouvement de va-et-vient des pistons 72, 73 sont réglables. Par ce mouvement, synchrone ou asynchrone, des pistons, on provoque un déplacement du bol alimentaire d'une chambre de compression C2 ou C3 vers l'autre chambre de compression C3 ou C2 à travers la chambre principale C8 et la flasque d'obturation 20 et éventuellement la chambre complémentaire Cg, situées entre les chambres C2, C3. Ces mouvements provoquent un écoulement turbulent du contenu dans l'ensemble du dispositif 1 , assurant un mélange homogène de celui-ci ainsi qu'un broyage peu "agressif vis-à-vis des composants solides. En d'autres termes, on reproduit de manière satisfaisante et représentative une digestion gastrique.To introduce a food bolus into the device, if necessary, the pistons 7 2 , 7 3 are separated from each other as the volume of the contents in the device increases. Conversely, the pistons I 2 , Iz will progressively approach each other as the content decreases, for example during racking, until returning to a predefined position. This variation in the volume of the contents during a cycle of operation depends on the entrances of the alimentary bolus and / or gastric secretions, the residence time of the bolus in the device 1 and racking done. The entries, the residence time and the withdrawal of the content of the device are variable depending on the digestive conditions to reproduce. The instantaneous volume of content present in the device 1 can be up to 600 milliliters. Alternate longitudinal displacements of the two pistons 7 2 , 7 3 are performed during an operating cycle of the device 1. The frequency and the speed of this reciprocating movement of the pistons 7 2 , 7 3 are adjustable. By this synchronous or asynchronous movement of the pistons, the food bolus is displaced from one compression chamber C 2 or C 3 to the other compression chamber C 3 or C 2 through the main chamber C 8 and the flange 20 and optionally the complementary chamber Cg, located between the chambers C 2 , C 3 . These movements cause a turbulent flow of the contents throughout the device 1, ensuring a homogeneous mixture thereof as well as a grinding that is not aggressive with respect to the solid components. satisfactory and representative way gastric digestion.
Le mélange et le broyage du contenu gastrique peuvent être optimisés par la présence de plusieurs flasques d'obturation, disposées dans le dispositif 1 , notamment entre la chambre principale C8 et une chambre de compression C2, C3, voire entre les chambres C8 et C9. Ainsi, on peut avoir un jeu de flasques, avec des orifices identiques ou non, que l'on utilisera en fonction des besoins, par exemple selon la réduction souhaitée de la taille des composants solides du bol alimentaire. Dans un autre mode de réalisation, le mélange et le broyage du bol alimentaire peuvent être améliorés par la présence de pièces de mise en turbulence ou chicanes, disposées soit dans la chambre de digestion Cs, soit au niveau des chambres C2, C3, soit dans les orifices 202 à 205 de la flasque 20. L'utilisation de pistons I2, 73 pour induire un mouvement du bol alimentaire dans les chambres C2, C3 permet une mise en mouvement complète, régulière et contrôlée du bol. On simule ainsi le tonus stomacal et donc on reproduit de manière représentative ce qui se passe lors de la digestion. Par ailleurs, le déplacement des pistons 72, 73, respectivement, dans les manchons 2, 3, combiné à un positionnement en butée contre les extrémités 22, 32, respectivement, en fin de cycle de digestion, pour le moins limite considérablement, voire annule, la présence de zones mortes dans les chambres C2, C3. Par ailleurs, les mouvements alternatifs des pistons réduisent considérablement, par un effet de type lessivage, la présence, en fin de cycle, de particules résiduelles non digérées dans la chambre Cs dont le volume utile est voisin de 60 millilitres.The mixing and grinding of the gastric contents can be optimized by the presence of several closure plates disposed in the device 1, in particular between the main chamber C 8 and a compression chamber C 2 , C 3 or even between the chambers C 8 and C 9 . Thus, one can have a set of flanges, with orifices identical or not, which will be used as needed, for example according to the desired reduction in the size of the solid components of the bolus. In another embodiment, the mixing and grinding of the food bolus can be improved by the presence of turbulence pieces or baffles, arranged either in the digestion chamber Cs or at the chambers C 2 , C 3 , or in the orifices 202 to 205 of the flange 20. The use of pistons I 2 , 7 3 to induce movement of the food bolus in the rooms C 2 , C 3 allows a complete, regular and controlled movement of the bowl. The stomach tone is simulated and therefore we reproduce in a representative way what happens during the digestion. Moreover, the displacement of the pistons 7 2 , 7 3 , respectively, in the sleeves 2, 3, combined with a positioning in abutment against the ends 22, 32, respectively, at the end of the digestion cycle, to say the least considerably, even cancel, the presence of dead zones in rooms C 2 , C 3 . In addition, the reciprocating movements of the pistons considerably reduce, by a leaching effect, the presence, at the end of the cycle, of undigested residual particles in the chamber Cs whose useful volume is close to 60 milliliters.
Avantageusement, le dispositif 1 est adapté pour étudier le comportement d'un produit à tester, celui-ci étant introduit et/ou retiré à tout moment d'un cycle de fonctionnement. Un tel produit à tester peut être par exemple un comprimé, un cachet, une gélule, une pâte, voire un liquide maintenu par un dispositif adapté. Pour cela, le bloc complémentaire 9 permet la mise en contact du contenu du dispositif avec le produit à tester préalablement déposé dans l'accessoire 17, au sein de la chambre intermédiaire Cg.Advantageously, the device 1 is adapted to study the behavior of a product to be tested, the latter being introduced and / or removed at any time from an operating cycle. Such a product to be tested may for example be a tablet, a cachet, a capsule, a paste, or even a liquid maintained by a suitable device. For this, the complementary block 9 allows the content of the device to come into contact with the test product previously deposited in the accessory 17, within the intermediate chamber Cg.
Avec le dispositif 1 on peut suivre, d'une part visuellement, à travers les manchons 2, 3, l'évolution du bol alimentaire, et d'autre part soutirer des échantillons du contenu du dispositif par l'orifice 10ç. With the device 1 can be followed, on the one hand visually, through the sleeves 2, 3, the evolution of the food bolus, and secondly draw samples of the contents of the device through the orifice 10c.

Claims

REVENDICATIONS
1. Dispositif de simulation d'un estomac d'un mammifère monogastrique ou d'un être humain, comprenant au moins deux chambres de compression (C2, C3) connectées entre elles par une chambre intermédiaire (Ce), caractérisé en ce que chaque chambre de compression (C2, C3) comporte un piston (72, 73 ) adapté pour pousser le contenu d'une chambre de compression (C2, C3) en direction de l'autre chambre de compression (C3, C2) et en ce qu'il comprend des moyens (20, 202, 203, 204, 205) aptes à provoquer un écoulement turbulent du contenu du dispositif (1) lors de son passage par une chambre intermédiaire (C8) ménagée dans un bloc intermédiaire (8) équipé d'au moins un moyen d'accès (10a, 10b, 10ç, 11a, 11b, 12, 13, 14, 15, 16 ,16a ) à la chambre intermédiaire (C8) permettant une alimentation en produits (12, 13, 14, 15) et/ou un soutirage du contenu (10a, 10b, 10ç) du dispositif (1) à tout moment du cycle de fonctionnement dudit dispositif (1).1. A device for simulating a stomach of a monogastric mammal or a human being, comprising at least two compression chambers (C 2 , C 3 ) connected to each other by an intermediate chamber (Ce), characterized in that each compression chamber (C 2 , C 3 ) comprises a piston (7 2 , 7 3 ) adapted to push the contents of a compression chamber (C 2 , C 3 ) towards the other compression chamber (C 3 , C 2 ) and in that it comprises means (20, 202, 203, 204, 205) capable of causing a turbulent flow of the contents of the device (1) during its passage through an intermediate chamber (C 8 ) arranged in an intermediate block (8) equipped with at least one access means (10a, 10b, 10c, 11a, 11b, 12, 13, 14, 15, 16, 16a) to the intermediate chamber (C 8 ) allowing a supply of products (12, 13, 14, 15) and / or a withdrawal of the contents (10a, 10b, 10c) of the device (1) at any time during the operating cycle of said device (1).
2. Dispositif selon la revendication 1 , caractérisé en ce que chaque piston (72, 73) est mobile selon une direction parallèle à un axe longitudinal (A-A') commun aux deux chambres de compression (C2, C3) et forme un fond mobile (72, 73) à chaque chambre (C2, C3).2. Device according to claim 1, characterized in that each piston (7 2 , 7 3 ) is movable in a direction parallel to a longitudinal axis (A-A ') common to the two compression chambers (C 2 , C 3 ) and forms a movable bottom (7 2 , 7 3 ) to each chamber (C 2 , C 3 ).
3. Dispositif selon la revendication 1 , caractérisé en ce que la chambre intermédiaire (C8) comprend deux cavités (80, 81 ) de forme et de dimensions différentes.3. Device according to claim 1, characterized in that the intermediate chamber (C 8 ) comprises two cavities (80, 81) of different shapes and sizes.
4. Dispositif selon la revendication 3, caractérisé en ce qu'une première cavité (80) est cylindrique à section circulaire et une seconde cavité (81 ) est configurée en L dont une branche (810) est reliée à la première cavité (80) et dont l'autre branche (81 1) est non débouchante dans les chambres de compression (C2, C3), en fonctionnement normal du dispositif (1). 4. Device according to claim 3, characterized in that a first cavity (80) is cylindrical with circular section and a second cavity (81) is configured in L, a branch (810) is connected to the first cavity (80) and whose other branch (81 1) is non-emergent in the compression chambers (C 2 , C 3 ) during normal operation of the device (1).
5. Dispositif selon la revendication 1 , caractérisé en ce que les moyens aptes à provoquer l'écoulement turbulent comprennent au moins une flasque d'obturation (20) montée entre une extrémité (22) d'une chambre de compression (C2) et une extrémité de la chambre intermédiaire (C8). 5. Device according to claim 1, characterized in that the means capable of causing the turbulent flow comprise at least one closure flange (20) mounted between one end (22) of a compression chamber (C 2 ) and one end of the intermediate chamber (C 8 ).
6. Dispositif selon la revendication 5, caractérisé en ce que la flasque (20) est pourvue d'au moins un orifice calibré (202 à 205) de passage du contenu du dispositif (1), d'une chambre de compression (C2, C3) à la chambre intermédiaire (Ce) et réciproquement. 6. Device according to claim 5, characterized in that the flange (20) is provided with at least one calibrated orifice (202 to 205) for passage of the contents of the device (1), a compression chamber (C 2 , C 3 ) to the intermediate chamber (Ce) and vice versa.
7. Dispositif selon la revendication 6, caractérisé en ce que la flasque d'obturation (20) est disposée de manière que son ou ses orifices (202 à 205) soient en regard d'une cavité cylindrique (80) de la chambre intermédiaire (C8).7. Device according to claim 6, characterized in that the closure flange (20) is arranged so that its orifices (202 to 205) are opposite a cylindrical cavity (80) of the intermediate chamber ( C 8 ).
8. Dispositif selon la revendication 1 , caractérisé en ce que le bloc intermédiaire (8) comprend un orifice d'accès (16) permettant l'introduction d'une sonde de pH et/ou de température dans la chambre intermédiaire8. Device according to claim 1, characterized in that the intermediate block (8) comprises an access port (16) for the introduction of a pH probe and / or temperature in the intermediate chamber
(C8).(C 8 ).
9. Dispositif selon la revendication 1 , caractérisé en ce que le bloc intermédiaire (8) comprend un orifice d'accès (16a) permettant l'introduction d'un capteur de pression dans la chambre intermédiaire (C8).9. Device according to claim 1, characterized in that the intermediate block (8) comprises an access port (16a) for introducing a pressure sensor into the intermediate chamber (C 8 ).
10. Dispositif selon l'une des revendications précédentes, caractérisé en ce qu'un bloc complémentaire (9) délimitant une chambre complémentaire (Cg), apte à recevoir un produit à tester dans le dispositif, est intercalé entre la flasque (20) et le bloc intermédiaire (8). 10. Device according to one of the preceding claims, characterized in that a complementary block (9) defining a complementary chamber (Cg), adapted to receive a product to be tested in the device, is interposed between the flange (20) and the intermediate block (8).
11. Dispositif selon la revendication 10, caractérisé en ce que le bloc complémentaire (9) délimitant la chambre complémentaire (C9) est intercalé de manière amovible entre la flasque (20) et le bloc intermédiaire (8).11. Device according to claim 10, characterized in that the complementary block (9) defining the complementary chamber (C 9 ) is interposed removably between the flange (20) and the intermediate block (8).
12. Dispositif selon l'une des revendications 10 ou 11 , caractérisé en ce que le bloc complémentaire (9) comprend un orifice (18) propre à recevoir un accessoire (17) destiné à contenir un produit à tester. 12. Device according to one of claims 10 or 11, characterized in that the complementary block (9) comprises an orifice (18) adapted to receive an accessory (17) for containing a product to be tested.
EP08870218A 2007-10-30 2008-10-21 Device for simulating the stomach of a monogastric mammal or of a human being Withdrawn EP2206098A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0707631A FR2923065B1 (en) 2007-10-30 2007-10-30 DEVICE FOR SIMULATION OF A STOMACH OF A MONOGASTRIC MAMMAL OR A HUMAN BEING
PCT/FR2008/001474 WO2009087314A1 (en) 2007-10-30 2008-10-21 Device for simulating the stomach of a monogastric mammal or of a human being

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EP2206098A1 true EP2206098A1 (en) 2010-07-14

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EP (1) EP2206098A1 (en)
CN (1) CN101896954B (en)
CA (1) CA2704159A1 (en)
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WO (1) WO2009087314A1 (en)

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CN101896954B (en) 2012-03-14
CN101896954A (en) 2010-11-24
US8257085B2 (en) 2012-09-04
FR2923065B1 (en) 2009-12-11
WO2009087314A1 (en) 2009-07-16
CA2704159A1 (en) 2009-07-16
FR2923065A1 (en) 2009-05-01
US20110020780A1 (en) 2011-01-27

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