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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• 2007
  • 2007-10-30 FR FR0707631A patent/FR2923065B1/fr not_active Expired - Fee Related
• 2008
  • 2008-10-21 WO PCT/FR2008/001474 patent/WO2009087314A1/fr active Application Filing
  • 2008-10-21 CA CA2704159A patent/CA2704159A1/fr not_active Abandoned
  • 2008-10-21 US US12/740,448 patent/US8257085B2/en not_active Expired - Fee Related
  • 2008-10-21 CN CN2008801199265A patent/CN101896954B/zh not_active Expired - Fee Related
  • 2008-10-21 EP EP08870218A patent/EP2206098A1/de not_active Withdrawn

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