WO2013190222A1

WO2013190222A1 - Device for manufacturing a therapeutic composite bar

Info

Publication number: WO2013190222A1
Application number: PCT/FR2013/051393
Authority: WO
Inventors: Blaise François Figuereo
Original assignee: Figuereo Blaise Francois
Priority date: 2012-06-18
Filing date: 2013-06-14
Publication date: 2013-12-27
Also published as: FR2991905B1; FR2991905A1

Abstract

The invention relates to a device for manufacturing a therapeutic composite bar having a plurality of components, characterized by the fact that said device includes: a connection box (1) including means for connection to extruders, and a guide part (9) for guiding the extrudates from each one of the extruders, consisting of a central channel (13) and of peripheral channels arranged around the central channel (13); and a die including a central channel and secondary channels, the die being attached to the connection box (1) at the outlet of the guide part (9), the central channel of the die expanding from the inlet of the die to the outlet of the die in order to enclose each one of the secondary channels of the die such that, at the outlet of the die, the outlet of the central channel of the die surrounds the outlet of each secondary channel of the die to form a composite bar having n coextruded components.

Description

MANUFACTURING A COMPOSITE BAR

THERAPEUTIC

The present invention relates to a device for manufacturing a therapeutic composite bar, allowing the manufacture of a composite therapeutic rod with several components, wherein one of the components encloses and separates the other components.

Extrusion methods and devices are well known in the art. They allow the formation of an extrusion bar with either a single component, or several dispersed components, or a core component surrounded by an envelope component.

The bars obtained by extrusion by known methods and devices are particularly used in the medical field where, after cutting and shaping by thermal polymerization or other means of cut bars, they adopt the shape of a ring. An example of a device used for the manufacture of such rings is, for example, described in French Patent FR 2,665,394 in the name of the present applicant, the same device having also been the subject of European patent EP 0 469 976 and the patent. US 5,133,234, also on behalf of the present applicant, and for manufacturing the Estring ® ring since 1992.

The bar thus formed in a ring is, for example, elastomer for medical use, for example intracorporeal silicone, and contains an active ingredient. For example, the Estring ® ring contains 2 mg of estradiol, diffusing in nanoflux at 7.5 pg per 24 hours, for a duration of 90 days. Used by patients intravaginally without medical intervention, these rings are used to release an active ingredient in the body, for hormone replacement therapy purposes, for prolonged periods of time (up to several tens of days). The Scientific Publication "Current and Future Microbicide Approaches Intended to Prevent HIV Infection in Women", Expert Review of Ant Infectious Therapy, February 2012 , Flight. 10, pages 167-183, thus describes an approach for preventing HIV infection by such rings.

The Estring ® ring has since been the subject of several marketing authorizations (MA) worldwide, including the US marketing authorization NDA 20-472, issued by the US Federal Agency. food and Drug Administration and the French marketing authorization h1.1p: / / af s saps - prd. afssaps. en / php / ecodex / excerpt .php ^' ? specid = 63806243

When a bar contains only one component / active ingredient, it is observed that the retrolarge spectrum of this component / active ingredient is regular.

By retrolargage spectrum is meant the nanoflux diffusion profile of the component / active ingredient from the bar to the body of the patient.

By regular retrolargage spectrum is meant a quantity of stable diffusion of the product over a prolonged period of time.

A typical dissemination profile of Estring ® can be viewed at http: / / user. it .uu.se / ~ j onasn / estr ing. htm.1 When a conventional therapeutic composite bar contains several components / active ingredients dispersed therein, it is observed that the retrolaying spectra of the various components / active principles are not regular, especially over a prolonged period. The non-regularity of the spectrum of retrolargage leads to an administration of the active ingredients which is not controlled and therefore a therapeutic inefficiency.

In order to allow new treatments based on the simultaneous use of several active ingredients having different properties, over a prolonged treatment period, there is a need for a therapeutic composite bar in which the different active ingredients have a regular nanoflow retrolay spectrum. , especially for several months.

The present invention responds to this need, and relates to a device for manufacturing an n composite composite bar, n being a natural integer greater than or equal to 3, characterized in that it comprises:

a connection box, comprising means for connection to n extruders, each extruder providing an extrudate constituting one of the n components of the composite bar, and a guide piece of the extrudates from each of the n extruders comprising a central channel and n-1) peripheral channels disposed around the central channel, each channel being intended to receive the extrudate of one of the n extruders; and

a die comprising n distinct channels, namely a central channel and (n-1) secondary channels, the die being fixed to the connection box at the outlet of the guide piece of the extrudates so that the inlet of the die center channel is aligned with the outlet of the center channel of the extrudate guide piece and each secondary channel inlet of the die is aligned with an outlet of one of the (n-1) channels peripherals of the extrudate guide piece, the central channel of the die flaring from the die inlet to the exit of the die to grip each of the (n-1) secondary channels of the die, so that At the outlet of the die the outlet of the die central channel surrounds the outlet of each secondary channel of the die to form a co-extruded composite n-component bar, (n-1) core components from the secondary channels of the die. the die clamped and separated from each other by an envelope component from the central channel of the die.

The die can for example be machined by a four-axis machining wire machine. Such machines are manufactured, for example, by the company Agie Charmilles.

The composite bar thus manufactured is, preferably, a therapeutic composite bar and contains n components separated from each other, each component may contain an active ingredient, for example for the manufacture of an intravaginal ring in which the active ingredients are separated each other, which avoids any interaction between said active ingredients. In practice, an envelope component encloses each of the core components that contain an active ingredient.

In addition, in an intravaginal ring made from a device according to the invention, the fact that the components containing an active ingredient are separated each other and located in the composite bar, each in a defined area, provides a regular retrolagging spectrum for each active ingredient over a prolonged period of time of wearing the intravaginal ring of up to 90 or even 120 days, and therefore a controlled administration of the active ingredient to a patient over this extended period of time. The safety of the patient is thus preserved, while providing the latter with effective therapy.

The device of the invention makes it possible to manufacture intravaginal rings with a prolonged duration of use compared to existing intravaginal rings, because of the separation of the active principles in the bar which makes it possible to obtain a regular retrolargage spectrum for each principle active over an extended period of time, and the possibility of simultaneously administering several active ingredients, each with a regular retrolargage spectrum.

The die can be detachably attached to the junction box, allowing it to be easily changed when worn by the extrusions.

According to a particular embodiment, the output region of each peripheral channel of the guide piece of the extrudates of the connection box and the input region of each secondary channel of the die can have an arcuate cross section of circle, the outputs of each peripheral channel of the guide piece of the extrudates being aligned on the same circle centered on the central channel of the guide piece of the extrudates and the inputs of each secondary channel of the die being aligned on the same centered circle on the central channel of the die. The guide piece does not include any expansion chamber which could create a back pressure of the extrudates, so as to ensure the stability of the extrudate after cutting on the fly by a cutting device at the output of the device of the invention.

The exit region of each secondary channel of the die may have a round section, or any other section, for example square or oval.

The junction box can carry annular protrusions each having a rim at their free end, the connecting means of an extruder being constituted by a ring fixed on both the rim of an annular projection and an extruder head. The inlet of each peripheral channel and the central channel of the extrudate guide piece is located at the base of each annular projection.

According to a particular characteristic of the invention, the connection box may furthermore comprise a heat transfer vehicle circulation circuit, an inlet and an outlet of the heat transfer vehicle circulation circuit being defined on one face of the connection box. The connection box can then be inserted into a heat-carrier circulation circuit for the circulation of a heat-carrying vehicle, in particular a fluid and in particular water, in the connection box to guarantee a certain temperature of the extrudates at the outlet. of the connection box.

It is thus possible to control the treatment and outlet temperature of the extrudates.

According to a particular characteristic of the invention, the guide piece of the extrudates may be a frustoconical piece, arranged in a housing corresponding frustoconical junction box, with the central channel formed on the axis of the frustoconical piece and the peripheral channels formed in the form of grooves on the lateral surface of the frustoconical piece, the channel inlets being at the base of the frustoconical piece and the outlets of the channels being at the top of the frustoconical piece.

The peripheral channels are formed between the grooves of the frustoconical piece and the walls of the frustoconical housing receiving the frustoconical piece.

The extrudate from the central channels of the guide piece and the die may be of elastomer for medical use, preferably intracorporeal silicone, optionally containing an active ingredient.

The extrudates from the peripheral channels of the guide piece and the die may be of elastomer for medical use, preferably intracorporeal silicone, containing an active ingredient. The active ingredients may be identical or different in the peripheral and secondary channels.

The device for manufacturing a composite bar may further comprise a cutting device disposed at the outlet of the die for cutting composite bars formed to a predetermined length. A cutting device adapted to the device of the invention is for example that described in the French patent FR 2,665,394 mentioned above.

According to a particular embodiment, n = 4 and the connection box may be of rectangular parallelepipedal shape, preferably cubic, four opposite side faces in pairs each carrying means for connection to an extruder, the outputs of the guide piece opening on one side of the housing of connection not carrying connection means to an extruder and on which is fixed the die.

The subject of the invention is also a system for manufacturing a composite bar, characterized in that it comprises a device for manufacturing a composite bar as defined above, on the connection box of which four extruders are connected for form a four-component composite bar.

According to a particular characteristic of the system, in operation, the worms of two of the extruders rotate in one direction and the worms of the other two extruders rotate in the opposite direction.

This avoids any torsion of the composite bar formed at the output of the die, which would otherwise be observed if the worm of the four extruders all turned in the same direction.

The invention also relates to a therapeutic composite bar, characterized in that it comprises a shell component enclosing three core components, manufactured from the system of the invention as defined above.

The composite bar thus has three core elements of generally cylindrical shape and parallel to each other, each core element comprising a component / active ingredient and a shell element, also cylindrical, enclosing the three core elements.

To better illustrate the object of the present invention, we will now describe a particular embodiment, by way of illustration and not limitation, with reference to the accompanying drawing.

On this drawing : Figure 1 is a partial sectional side view of a junction box of the composite bar manufacturing device according to the present invention; Figure 2 is a bottom view of the junction box of Figure 1; Figure 3 is a top view of the junction box of Figure 1, connected to four extruders; Figure 4 is a side view of a clamping ring of the junction box of Figure 1 with an extruder;

- Figure 5 is a schematic view of the interior of a die of the device according to the invention, schematically showing the inputs of the three secondary channels and the outputs of the three secondary channels and the main channel; Figure 6 is a top view of the die of the device of the invention; - Figure 7 is a sectional view of the die of Figure 6, along the line VII-VII of Figure 6; Figure 8 is a schematic bottom view of the die of Figure 6, showing the different channels formed within the die; and Figure 9 is a bottom view of the die of Figure 6. Referring to Figures 1 to 3, it can be seen that there is shown a connection box 1 of a composite bar manufacturing device according to the present invention.

The junction box 1 is of cubic shape, and comprises, in the position of use shown in FIG. 1 with only two extruders E1 and E3 shown, four lateral faces 2, 3, 4 and 5, an upper face 6 and a face lower 7.

The junction box 1 comprises an upper block 1A and a lower block 1B in one piece.

The upper block 1A comprises a central cavity 8, extending in the lower block 1B into a central frustoconical cavity 20, narrowing towards the lower face 7, opening onto a central hole 21 formed on the lower face 7.

Recesses 14, 22 are formed in the middle of each lateral face 2, 3, 4 and 5 of the connection box 1, the recesses 14, 22 being of frustoconical shape, narrowing towards the inside of the connection box 1. The part upper 14 of each recess is formed in the upper block 1A, its lower part 22 is formed in the lower block 1B.

The recesses 14, 22 form a truncated cone-shaped opening for receiving an endless screw of an extruder (worm VI of the extruder E1 in FIG. 1).

A ring 15, 23 is formed around each recess 14, 22, the upper part 15 of the ring being formed on the upper block 1A of the connection box 1, the lower part 23 of the ring being formed on the lower block 1B of the connection box 1, in one piece with the upper part 15.

A flange is formed on the free end of the ring 15, 23, with an upper flange portion 16 and a lower flange portion 24, the ring 15, 23 with its flanges 16, 24, non-continuous on the periphery of the ring 15, 23, forming a firemen connection on each lateral face 2, 3, 4 and 5 of the connection box 1.

An annular projection with a flange at its free end is thus formed in the center of each side face 2, 3, 4 and 5 of the connection box 1, for connecting an extruder, as will be described below.

A part 9 comprising a frustoconical portion 9B and a rod 9A extending from the end of larger diameter of the frustoconical portion 9B along the axis of the frustoconical portion 9B, extends into the connection box 1, the portion frustoconical 9B being received in the frustoconical cavity 20 of the lower block 1B, the rod 9A extending into the central cavity 8 of the upper block 1A until protruding therefrom.

Four channels are formed on the frustoconical portion 9B, three peripheral channels 10, 11 and 12 formed in the form of grooves on the frustoconical face of the frustoconical portion 9B, and a central channel 13, pierced along the axis of the frustoconical portion 9B, each channel 10, 11, 12 and 13 opening into a respective recess 14, 22 when the part 9 is in position in the connection box 1. The extrudate from each extruder connected to the connection box 1 is thus made to pass into a respective channel 10, 11, 12 and 13.

A locking piece (nut) 17 is screwed onto a threaded step 1AA formed in the upper part of the cavity 8, and maintains the piece 9 by clamping its rod 9A in a sleeve 18, a key 18A being disposed between the sleeve 18 and the rod 9A, a key 19 further to index the part 9 centered in the connection box 1, so that the respective channels 10, 11, 12 and 13 each open into one of the recesses formed on the side faces 2, 3, 4 and 5 of the connection box 1.

A circlip 17A and 17B friction washers, respectively in the upper part and in the lower part of the locking piece 17 and tightening the rod 9A, allow the driving of the rod 9A and therefore of the piece 9 with the screwing / unscrewing of the locking piece 17 on the upper part of the connection box 1.

An annular recess 25 is formed in the lower block 1B around the frustoconical cavity 20, the annular recess 25 opening on the lower face 7 of the lower block 1B and being closed on this face by a cover 26.

A heat transfer vehicle circulation channel

27 is formed in the connection box 1, said channel 27 having an inlet 27A and an outlet 27B both located on the upper face 6 of the connection box 1, the circulation channel of the heat transfer vehicle 27 flowing in the recess 25 to achieve a heat exchange with the extrudates passing through the lower block 1B.

Once the part 9 has been introduced into the junction box 1, the peripheral channels 10, 11 and 12 are formed between the grooves on the frustoconical piece 9 and the wall of the frustoconical cavity 20. The cross section of the outlets 10A, 11A, 12A of each peripheral channel, respectively 10, 11 and 12, is in the shape of an arc of a circle, the three outlets 10A, 11A, 12A being aligned on the same circle centered around the round outlet 13A in cross section of the central channel 13.

The frustoconical portion 9 thus constitutes a guiding piece of the extrudates from extruders El, E2, E3 and E4.

The extruders E1, E2, E3 and E4 are connected to the junction box 1 by centering pins 28 fixed on the flanges 16 and 24 and on corresponding peripheral annular rims 29 formed on the extruders E1, E2, E3 and E4.

An annular ring 30 shown in FIG. 4 and joining the flanges 16 and 24 of the connection box 1 on the one hand, and 29 of the extruders on the other hand, makes it possible to effectively secure the connection box 1 to the extruders E1, E2, E3 and E4. The annular rings 30 are integral with the extruders E1, E2, E3 and E4, and are fixed on the flanges 16 and 24 of each side face of the connection box 1 in the manner of a firefighter connection.

The annular ring 30 has radial bores 31 in each of which are inserted needle screws 32, the tip of which engages with the free bevelled edges of the flanges 16 and 24 of the connection box 1 and 29 of each extruder.

A projecting element 33 of the lower face of the connection box 1 serves as a key for fixing to the connection box 1 of the bushing described in more detail below.

Similarly, a disc 34 projecting from the lower face 7 is formed at the outlet of the part 9, disc 34 in which are formed the outputs 10A, 11A, 12A and 13A peripheral channels 10, 11 and 12 and the central channel 13.

Referring to Figures 5 to 9, it can be seen that there is shown the die 35 according to the invention.

The die 35 is disk-shaped, plated and fixed to the lower surface of the connection box 1 by fastening elements (not shown) passing through cavities 35A, 35B, 35C, 35D formed in the thickness of the die. 35, the hole 35B having an enlarged base 35B1 for receiving the polarizer 33 to ensure the correct positioning of the die 35 on the connection box 1.

The die 35 is a wear part intended to be changed once worn, and must therefore be removably attached to the connection box 1.

The die 35 has an upper face 36, in contact in use with the underside of the connection box 1, and an opposite lower face 37 from which is extruded the final composite bar.

The lower face 36 has a disc-shaped central recess 38, complementary to the disc 34 formed on the underside of the connection box 1 to receive it when fixing the die 35 to the connection box 1 and ensure a good positioning and close contact between these two elements.

Four channels 39, 40, 41 and 42 are formed through the die 35, the channels 39, 40, 41 and 42 having their inputs 39A, 40A, 41A and 42A respectively formed in the bottom of the recess 38 and opening through their outlets 39B, 40B, 41B and 42B on the lower face 37 of the die 35. The inputs 39A, 40A, 41A are analogous to the outputs of the peripheral channels 10A, 11A and 12A of the junction box 1, that is to say each have a cross-sectional section in the form of an arc of a circle and are all three arranged on the same circle centered on the input 42A of the channel 42, the input 42A of the channel 42 having a cross-section in the form of a circle of the same diameter as the output 13A of the channel 13.

Thus, when the junction box 1 and the die 35 are assembled, the outputs 10A, 11A and 12A of the peripheral channels 10, 11 and 12 are aligned with the inputs 39A, 40A, 41A of the channels 39, 40 and 41 and the output 13A of the central channel 13 is aligned with the input 42A of the channel 12, so that the extrudates from the peripheral channels 10, 11 and 12 pass in the channels 39, 40 and 41 and that the extrudate from the central channel 13 goes into the channel 42.

The channels 39, 40 and 41 extend to their respective outlets 39B, 40B and 41B, their cross sectional sections being modified so that the outputs

39B, 40B and 41B are round, as shown schematically in Figure 5.

The central channel 42 also sees its cross-sectional cross section to change from its round entry 42A on the face 36 to its exit surrounding each of the exits 39B,

40B and 41B and having a cross-sectional section rounded on the face 37.

Thus, the channel 42 is diffused along three branches 421, 422 and 423 between the three channels 39, 40 and 41, the three branches joining an annular recess

424 formed in the lower part of the die 35, around the channels 39, 40 and 41, so that the extrudate from the channel 42 surrounds the three extrudates from the three channels 39, 40 and 41 and has a section in round cross section, thus forming the composite bar with three core extrudates from the channels 39, 40 and 41 enclosed by an envelope extrudate from the channel 42.

Claims

1 - Device for manufacturing an n composite composite bar, n being a natural integer greater than or equal to 3, characterized in that it comprises:

a connection box (1) comprising connection means (30) with n extruders, each extruder supplying an extrudate constituting one of the n components of the composite bar, and a guide piece (9) of extrudates from each of extruders comprising a central channel (13) and (n-1) peripheral channels (10, 11, 12) arranged around the central channel (13), each channel (10, 11, 12, 13) being adapted to receive 1 extrudate of one of the n extruders; and

- a die (35) comprising n distinct channels, namely a central channel (42) and (n-1) secondary channels (39, 40, 41), the die (35) being fixed to the connection box (1) to the outlet of the guide piece (9) from the extrudates such that the inlet of the central channel (42) of the die (35) is aligned with the outlet of the central channel (13) of the guide piece (9) extrudates and that each secondary channel inlet (39A, 40A, 41A) (39, 40, 41) of the spinneret (35) is aligned with an outlet (10A, 11A, 12A) of one of the (n-1) ) peripheral channels (10, 11, 12) of the guide piece (9) of the extrudates, the central channel (42) of the die (35) flaring from the inlet of the die (35) to the exit of the die (35) to enclose each of the

(n-1) secondary channels (39, 40, 41) of the die (35), so that at the output of the die (35) the outlet (42A) of the central channel (42) of the die (35) ) surrounds the output (39B, 40B, 41B) of each secondary channel (39, 40, 41) of the die (35) to form a co-extruded n component composite bar, (n-1) core components from secondary channels (39, 40, 41) of the die (35) clamped and separated from one another by an envelope component from the central channel (42) of the die (35).

2 - device for manufacturing a composite bar according to claim 1, characterized in that the output region of each peripheral channel (10, 11, 12) of the guide piece (9) of the extrudates of the connection box ( 1) and the input region of each secondary channel (39, 40, 41) of the die have an arcuate cross-section, the outputs (10A, 11A, 12A) of each peripheral channel (10, 11, 12) of the guide piece (9) of the extrudates being aligned on the same circle centered on the central channel (13) of the guide piece (9) of the extrudates and the entries (39A, 40A, 41A) of each secondary channel (39, 40, 41) of the die (35) being aligned on the same circle centered on the central channel (42) of the die (35).

3 - Device for manufacturing a composite bar according to claim 1 or claim 2, characterized in that the output region of each secondary channel (39, 40, 41) of the die (35) has a round section.

4 - Device for manufacturing a composite bar according to one of claims 1 to 3, characterized in that the connection box (1) carries annular projections (15, 23) each having a flange (16, 24) at their free end, the connecting means (30) of an extruder being constituted by a fixed ring both on the flange (16, 24) with an annular projection (15, 23) and an extruder head.

5 - device for manufacturing a composite bar according to one of claims 1 to 4, characterized in that the connection box (1) further comprises a heat transfer vehicle circulation circuit (27), an inlet (27A ) and an outlet (27B) of the heat transfer vehicle circulation circuit (27) being defined on one side of the connection box (1).

6 - Device for manufacturing a composite bar according to one of claims 1 to 5, characterized in that the guide piece (9) of the extrudates is a frustoconical piece, disposed in a corresponding frustoconical housing (20) of the housing connecting piece (1), with the central channel (13) formed on the axis of the frustoconical piece and the peripheral channels (10, 11, 12) formed in the form of grooves on the lateral surface of the frustoconical piece, the entries of channels being at the base of the frustoconical piece and the outlets (10A, 11A, 12A, 13A) of the channels (10, 11, 12, 13) being at the top of the frustoconical piece.

7 - Device for manufacturing a composite bar according to one of claims 1 to 6, characterized in that the extrudate from the central channels (13; 42) of the guide piece (9) and the die ( 35) is elastomer for medical use, preferably intracorporeal silicone, optionally containing an active ingredient.

8 - Device for manufacturing a composite bar according to one of claims 1 to 7, characterized in that the extrudates from the peripheral channels (10, 11, 12; 39, 40, 41) of the guide piece ( 9) and the die (35) are elastomeric to medical use, preferably intracorporeal silicone containing an active ingredient.

9 - Device for manufacturing a composite bar according to one of claims 1 to 8, characterized in that it further comprises a cutting device disposed at the outlet of the die (35) for cutting composite bars formed to a predetermined length.

10 - Device for manufacturing a composite bar according to one of claims 1 to 3, characterized in that n = 4 and that the connection box (1) is rectangular parallelepiped shape, preferably cubic, four side faces (2, 3, 4, 5) opposed in pairs, each carrying means for connection (30) to an extruder, the outputs of the guide piece (9) opening on one face (7) of the connection box (1) not carrying connection means to an extruder and on which is fixed the die (35).

11 - System for manufacturing a composite bar, characterized in that it comprises a composite bar manufacturing device according to one of claims 1 to 10, on the connecting box (1) which are connected four extruders ( E1, E2, E3, E4).

12 - therapeutic composite bar, characterized in that it comprises a shell component enclosing three core components.