WO2017017381A1

WO2017017381A1 - Multi-component filament comprising alginate

Info

Publication number: WO2017017381A1
Application number: PCT/FR2016/051959
Authority: WO
Inventors: Emeline MARTEAU; Stéphane Lack; Christian Girardiere
Original assignee: Les Laboratoires Brothier
Priority date: 2015-07-30
Filing date: 2016-07-28
Publication date: 2017-02-02
Also published as: FR3039565B1; EP3329040B1; EP3329040A1; ES2870175T3; FR3039565A1

Abstract

The invention relates to a multi-component filament (1) comprising alginate (A), characterised in that it has a heterogeneous structure and comprises multiple different parts (2A, 2AB, 2B, 2C), of which: at least one part (2A) comprises an alginate (A); and at least one part (2AB, 2B, 2C) comprises a polymer (B, C) other than alginate (A).

Description

M ulti-com pos alginate filament

TECHNICAL AREA

The present invention relates to a multi-component filament based ^on alginate. It also relates to the compounds obtained from this filament. These products are advantageously used in the treatment of wounds and are in particular intended for hemostasis and cicatrization. The invention also relates to a device for manufacturing the filament and a method of manufacturing the filament.

STATE OF THE ART

Alginic acid and its derivatives (base conjugates, salts and esters) alginates are polysaccharides mainly obtained from a family of brown algae: laminaria or fucus.

Alginate is the common name for a family of polymers consisting of two monomers bonded together: mannuronate or mannuronic acid and guluronate or guluronic acid.

The general formula of alginate is as follows:

The proportion and distribution of these two monomers are decisive for a broad expansion of the physical and chemical properties of alginate, so-called gluronic mannuronic ratio or M / G ratio. Its chemical composition varies among different species of algae, different parts of the same plant and is subject to seasonal changes. Nevertheless, by selecting raw materials with different properties, it is possible to manufacture a variety of alginate with constant characteristics. _^

Products based on alginate, in particular calcium alginate, have intrinsic, natural, very effective properties against wound treatment. These products are in particular intended for hemostasis and cicatrization.

Indeed, calcium alginate has a double beneficial action: it facilitates both coagulation and healing. In contact with the lesion, the alginate exchanges its Ca + ions with the Na + ions of the biological fluids, thus activating the cells involved in healing. In addition, the alginate fibers gel, creating a moist environment conducive to the healing process. It therefore has a high absorption capacity, superior to that of hydrocolloids and hydrocellulars. Calcium alginate therefore has healing properties.

Moreover, this natural substance has the advantage of having a property of hemostasis. Its effectiveness results from local activation of coagulation by calcium ions. Alginate fibers are also a matrix for structuring and strengthening the blood clot network.

Alginate fibers further reduce the risk of infection locally by attaching lesion bacteria to its gelled fiber network. Finally, alginate does not induce the proliferation of germs responsible for toxic shock syndrome.

The alginate can be manufactured in the form of filaments. From these filaments can be obtained fibers, yarns, fabrics, knits, lace, wadding, compresses and any other textile product. Among their applications, the use of yarns as suture material and the use of tissues, wicks, wadding, etc., as haemostatic and healing dressings in particular can be cited.

It is known from US 2009/0099353 an alginate fiber and chitosan. This fiber, which has a homogeneous structure, does not allow local control of the action of alginate and chitosan. It appears desirable to have textile products comprising alginate and in which one can associate with the alginate at least one other active ingredient and to choose locally in the product the zones of action of the alginate and the zones of action of the other active ingredients. It is also desirable to control the distribution and the amounts of these properties, without the different properties of the active ingredients interfere.

The present invention aims to achieve this objective. SUMMARY OF THE INVENTION

The subject of the invention is thus a multi-component filament based on alginate.

The filament according to the invention is of heterogeneous structure and comprises several distinct parts, of which:

at least one part comprising an aiginate, for example a part comprising an aiginate as sole polymer, and

at least one part comprising a polymer different from said aiginate.

By "polymer different from said aiginate" is meant a polymer of different structure of the alginate, for example of different formula, or of arrangement in the different space. The different polymer of said aiginate may thus be another aiginate, of different formula, for example of different M / G ratio. The different polymer of said aiginate may also be an aiginate of the same formula, but of different spatial arrangement, for example different crosslinking, or orientation of the polymer chains in the different space.

By "distinct parts" in the sense of the invention is meant parts separated from each other, which do not mix. The distinct parts are in particular of different structures.

Thus, advantageously, said at least one part comprising the alginate is distinct is separated from the other part or parts. This Filament sequencing has the advantage that each part locally confers the property associated with the polymer it contains. The parts being distinct, the different properties associated with the different polymers do not interfere.

The presence of distinct parts implies that the filament does not have a uniform and uniform composition, especially along the filament. In particular, the filament does not consist of a homogeneous mixture of the alginate and the different polymer of the alginate. It is the combination of the different distinct parts that causes the heterogeneity of the filament.

Each distinct part may be of homogeneous composition, and may be monophasic, the filament comprising at least two different phases.

Said at least one part comprising a polymer different from said alginate may not comprise said alginate.

Said plurality of distinct parts may be arranged longitudinally and / or transversely. Longitudinal arrangement means that the filament has a single portion in cross section. By transverse arrangement is meant that the filament has in cross section several of said distinct parts.

Preferably, for example in the case of transverse arrangement, the filament has in cross section several distinct non-concentric parts. In particular, in cross section, each portion advantageously forms a portion of the periphery of the filament, so that each polymer is present on the periphery of the filament and thus constitutes an action zone. For example, the filament having a circular cross section, each portion may have a disc-shaped cross section (sector).

In the same way, in case of longitudinal arrangement, the filament being cylindrical, each distinct part may constitute a cylindrical portion of the filament. More generally, said at least one part comprising an alginate and said at least one part comprising a polymer different from said alginate each form at least a part of the periphery (outer rim) of the filament, said part of the periphery thus constituting a zone of local action active ingredient.

The filament may comprise an alternation of a portion comprising alginate and at least a portion comprising a polymer different from said alginate.

Said alternation may comprise, between the portion comprising alginate and said at least a portion comprising a polymer different from said alginate, a part comprising a monophasic mixture of the alginate and said other polymer.

The alginate may be an alginate of a metal selected from the family of multivalent metals, with the exception of magnesium.

The alginate may be calcium alginate.

Said polymer different from said alginate may be chosen from polymers having a flexibility activity, hemostatic, healing, antibacterial, thermomechanical, or fast resorption.

The filament may be obtained by coextrusion of an alginate and at least one polymer different from said alginate.

The invention also relates to a textile product comprising at least one heterogeneous filament described above.

The textile product can be chosen from fibers, threads, fabrics, locks, knits, lace, wadding and compresses.

The invention also relates to the use of a textile product described above for the manufacture of a suture material or a dressing.

The invention also relates to a device for manufacturing a heterogeneous filament described above.

The device according to the invention comprises extrusion means capable of passing, in particular under pressure, through the same die extruding, successively and / or simultaneously, a composition comprising an alginate and at least one composition comprising a polymer different from said alginate, and in particular a composition comprising a polymer different from said alginate and not comprising said alginate.

The device advantageously comprises control means capable of controlling a successive and / or simultaneous passage of said composition comprising an alginate and said at least one composition comprising a polymer different from said alginate.

The successive passage can be provided by means of valves, for example using a three-way valve in the case where there are two compositions, or by arranging a valve between each composition and the extrusion die .

The extrusion means may comprise first means capable of passing under pressure said composition comprising an alginate through the die, and at least second means able to pressurize said at least one composition comprising a polymer different from said alginate. through the industry.

Each of said first and at least second means may comprise a jack and a syringe. This cylinder-syringe assembly can be advantageously replaced by a pressurized container.

The device may comprise downstream of the extrusion die a tank containing a crosslinking agent, and a drying device.

The invention also relates to a method of manufacturing a heterogeneous filament described above.

The method according to the invention comprises a step in which a composition comprising an alginate and at least one composition comprising a polymer different from said alginate is passed through, especially under pressure, through the same extrusion die, successively and / or simultaneously. and not including said alginate. A successive passage of the compositions makes it possible to obtain a longitudinal arrangement of the distinct parts, while a simultaneous passage of the compositions makes it possible to obtain a transverse arrangement of the distinct parts.

The method may comprise a repetition of said step, the number of repetitions being a function of the number of distinct parts desired in the filament.

DESCRIPTION OF THE FIGURES

The invention will be better understood and other details, characteristics and advantages of the invention will appear on reading the following description given by way of nonlimiting example and with reference to the appended drawings in which:

- Figures 1 to 4 schematically illustrate a portion of a filament according to the invention, according to different embodiments,

FIG. 5 is a schematic view of a device for manufacturing a filament according to the invention, according to a first embodiment, and

- Figure 6 a schematic view of a device for manufacturing a filament according to the invention, according to a second embodiment.

DETAILED DESCRIPTION

A multi-component filament according to the invention comprises several distinct parts, at least one part comprising an alginate and at least one part comprising another polymer. In a first embodiment, as illustrated in FIG. 1, a filament 1 according to the invention, for example cylindrical, comprises an alternation of a cylindrical sequence 2A comprising an alginate (polymer A) and a cylindrical sequence 2B comprising a polymer B and not comprising polymer A. In a second embodiment (FIG. 2), similar to the first embodiment, filament 1 comprises, between sequences 2A and 2B, a cylindrical sequence 2AB comprising only as polymers a single-phase mixture of alginate A and polymer B .

In a third embodiment (FIG. 3), the filament 1 comprises an alternation of a cylindrical sequence 2A comprising an alginate A, a cylindrical sequence 2B comprising a polymer B and not comprising polymer A and a sequence cylindrical 2C comprising a polymer C and not comprising polymer A.

In a fourth embodiment (FIG. 4), the filament 1 comprises two distinct sequences 2A and 2B, but which are this time transversally adjacent. Unlike the first three embodiments, in which the distinct portions are distributed only longitudinally (the filament has a single sequence in cross-section), the filament 1 comprises in this embodiment transversely associated sequences (the filament 1 has a cross-section a sequence 2A and a sequence 2B in the form of circular sectors). The filament 1 may thus comprise a sector 2A, for example a half-disc, comprising an alginate (polymer A) and a sector 2B, for example a half-disc, comprising a polymer B and not comprising a polymer A. Each polymer A and B is thus active on half of the circumference of the filament.

The fourth embodiment may also be combined with one of the first three embodiments.

Any type of sequencing may be chosen along the filament 1, and in particular any number of polymers and any relative arrangement of the polymers between them, depending on the desired use.

We thus see the interest of the structure, in separate parts, separated and not confused: we can choose locally along the filament the polymer and therefore its associated property. In addition, the properties of the different polymers do not interfere.

As examples of properties conferred by the various polymers, mention may be made of:

the rigidity, conferred for example by guluronic alginate (polymer A),

the flexibility conferred for example by mannuronic alginate (polymer B),

the hemostatic activity, conferred for example by mannuronic alginate (polymer B),

the healing activity, conferred for example by guluronic alginate (polymer A) or hyaluronic acid (polymer B),

the antibacterial or bacteriostatic activity conferred for example by an alginate with a silver salt (polymer B),

the thermomechanical activity (elongation, rigidity as a function of temperature), conferred for example by the polymers sold under the name ExpertGel® by the company PolymerExpert, and in particular the ExpertGel® EG56 and ExpertGel® EG230 polymers (polymer B),

rapid resorption, conferred for example by polycaprolactone, polyglycolic acid (polymer B), polylactic acid (polymer B), glycolic acid and lactic acid copolymer (polymer B), polydioxanone (polymer B).

The filament can thus have an alternation of sequences having the following properties:

- rigid - flexible,

- hemostatic - healing,

- slow resorption - fast absorption,

- healing - antibacterial.

Dyes can be included in the various sequences to easily identify the properties. For example, one can use a pink dye for the filament sequence conferring antibacterial activity and a green dye for the filament sequence conferring hemostatic activity.

FIG. 5 illustrates an example of a device 3 for manufacturing a filament according to the invention. The device comprises two cylinders 4A, 4B each actuating a syringe 5A, 5B. The syringe 5A comprises a composition comprising the polymer A (alginate) as the active ingredient, for example a composition comprising the polymer A as the sole polymer, and the syringe 5B comprises a composition comprising the polymer B as a active ingredient, for example a composition comprising polymer B and not comprising polymer A.

Each syringe 5A, 5B is connected to an extrusion die 6 from which fires one or more filaments 1 according to the invention.

The device 3 comprises two valves 7A, 7B, including a valve 7A placed on a pipe 8A connecting the syringe 5A to the die 6, and a valve 7B placed on a pipe 8B connecting the syringe 5B to the die 6.

The device 3 also advantageously comprises, at the outlet of the die 6, a reservoir 9 comprising a crosslinking agent, as well as a drying device 10.

The device 3 is shown with two extrusion paths, in the case where the filament 1 comprises two types of sequences 2A and 2B. More extrusion paths can be envisaged depending on the number of polymers that it is desired to sequence in filament 1.

In order to obtain a filament 1 according to the invention, a composition, in particular an aqueous composition, comprising an alginate A in the syringe 5A and a composition, in particular an aqueous composition, comprising a polymer B and not comprising the polymer A in the syringe 5B. As alginate A, it is possible to use a water-soluble alginate, and in particular an alginate of a metal chosen from the family of multivalent metals, with the exception of magnesium, typically alginate of sodium. The polymer B may be chosen from the polymers B mentioned above, depending on the property that it is desired to confer on the sequences 2B of the filament 1.

To obtain a sequencing of a filament according to one of the three embodiments illustrated in FIGS. 1 to 3, that is to say an embodiment in which the sequences 2A.2B are arranged one after the other longitudinally, alternately injected either of the compositions of A and B in the die 6. The injection is carried out by pressurizing the syringes 5A or 5B using the cylinders 4A.4B. Pressure continuity is preferably used, so as to obtain alternating and continuous spinning.

Thus, to obtain a 2A polymer A sequence, the valve 7B connecting the syringe 5B is closed to the die 6, while the composition of A is injected into the die 6 via the valve 7 kept open. Similarly, to obtain a 2B polymer B sequence, the valve 7 A is closed connecting the syringe 5A to the die 6, while the composition of B is injected into the die 6 via the valve 7B kept open.

To obtain a sequencing of a filament according to the embodiment illustrated in FIG. 4, that is to say an embodiment in which the sequences 2A.2B are arranged one beside the other transversely, the composition of A and the composition of B are simultaneously injected into the die 6, via the valves 7 A and 7 B kept open. It is ensured that the compositions of A and B are immiscible so that the sequences 2A and 2B remain distinct.

The length of the sequences 2A, 2B can be adjusted by adjusting the pressure of the cylinders 4A.4B and the injection duration of the compositions of A and B. The injection time and the pressure are independently adjustable for the composition of A and the composition of B.

The number of filaments 1 at the outlet of the die 6 is related to the number of holes present in the die. A single hole die can be used to obtain a single filament 1, typically in the where it is desired to manufacture a suture. It is also possible to implement a die with several holes, so as to obtain several filaments.

The gel obtained at the outlet of the die 6 is advantageously crosslinked by passing through the reservoir 9 which contains the crosslinking agent. The crosslinking agent may be any agent allowing the crosslinking of the sequenced gel leaving the die 6, and in particular an acid solution or a solution of an alkaline earth salt, for example a calcium salt such as calcium chloride. The crosslinking allows a better mechanical strength of the filament 1.

The heating device 10 advantageously makes it easier to use the filament 1 obtained. Any type of heating device can be used, such as infrared heating.

The filament obtained for use in the manufacture of a textile product, for example a textile product selected from fibers, yarns, fabrics, locks, knits, laces, wadding, and compresses.

Wire means a set of at least one filament not cut longitudinally. By fiber is meant a set of at least one longitudinally cut filament.

In the embodiment illustrated in FIG. 6, in which the elements identical to those of FIG. 5 bear the same references, the device 3 may comprise, in place of the two valves 7A and 7B, a three-way valve 7. manufacturing a filament m ulti -composing

A first solution ^of sodium alginate was prepared by dissolving in 1 L of a 100 g aqueous solution of an alginate having an M / G ratio of 2. The solution is then homogenized with a reactor. In parallel, another solution is prepared in the same way with the same alginate but solubilizing 60 g of the alginate in 1 L. It is thus obtained a solution of 10% sodium alginate and a 6% solution. Due to the difference in concentration between the solutions, the viscosities of the solutions and therefore their behavior during the extrusion differ.

The solutions are then introduced into their respective containers, for example the syringes 5A and 5B of the device described above, which is pressurized, namely 1.5 bar for the 6% solution and 3 bar for the solution. at 10%.

The duration of injection of each of the solutions is 40 seconds and it is chosen to make ten alternations of each of the injections.

The solutions are thus alternately injected into a bath 9 of calcium chloride (FIGS. 5 and 6) which is here the crosslinking agent.

The gel thus formed is stretched and dried with a blower ^of hot air 10 (Figures 5 and 6), which forms the block 1 filament.

The advantage of this sequenced filament is to provide different tensile strengths and elongations at break depending on the sequences. Thus, the tensile strength of the M / G = 2% calcium alginate sequences is 3.84 N while the rupture strength of the M / G calcium alginate sequences is 2 to 6% is 1.67 N. The elongation at break of calcium alginate M / G = 2 to 10% ratio is 7.45 mm while the elongation at break of the sequences calcium alginate M / G = 2 to 6% is 13.94 N.

An optimization of the length of the sequences makes it possible to obtain a resistant filament which easily leads to the production of a textile product by knitting thanks to the flexible filament sequences.

Claims

1. Multi-component filament (1) based on aiginate (A), characterized in that it is of heterogeneous structure and comprises several distinct parts (2A, 2AB, 2B, 2C), of which:

at least a portion (2A) comprising an alginate (A), and

at least one part (2AB, 2B, 2C) comprising a polymer (B, C) different from said alginate (A).

2. Filament (1) according to claim 1, characterized in that said at least one portion (2B, 2C) comprising a polymer (B, C) different from said alginate (A) does not include said alginate (A).

3. Filament (1) according to claim 1 or 2, characterized in that said several distinct parts (2A, 2AB, 2B, 2C) are arranged longitudinally and / or transversely.

4. Filament (1) according to one of claims 1 to 3, characterized in that it comprises an alternation of a portion (2A) comprising alginate (A) and at least a portion (2B, 2C) comprising a polymer (B, C) different from said alginate (A).

5. Filament (1) according to claim 4, characterized in that said alternation comprises between the portion (2A) comprising alginate (A) and said at least a portion (2B.2C) comprising a polymer (B, C) different from said alginate (A), a portion (2AB) comprising a monophasic mixture of the alginate (A) and said polymer (B, C) different from said alginate (A).

6. Filament (1) according to one of claims 1 to 5, characterized in that the alginate (A) is an alginate of a metal selected from the family of multivalent metals, with the exception of magnesium.

7. Filament (1) according to claim 6, characterized in that the alginate (A) is calcium alginate.

8. Filament (1) according to one of claims 1 to 7, characterized in that said polymer (B, C) different from said alginate (A) is selected from polymers having flexibility, haemostatic, healing, antibacterial, thermomechanical, or rapid resorption activity.

9. Filament (1) according to one of claims 1 to 8, characterized in that it is obtained by coextrusion of an alginate (A) and at least one polymer (B, C) different from said alginate (A). ).

10. Textile product, characterized in that it comprises at least one heterogeneous filament (1) according to one of claims 1 to 9.

1 1. Textile product according to claim 10, characterized in that it is selected from fibers, threads, fabrics, locks, knits, lace, wadding, and compresses.

12. Use of a textile product according to claim 10 or 1 1 for the manufacture of a suture material or a dressing.

13. Device (3) for manufacturing a heterogeneous filament (1) according to one of claims 1 to 8, characterized in that it comprises extrusion means (4A, 4B, 5A, 5B, 7A, 7B , 8A, 8B) adapted to pass, in particular under pressure, through a same extrusion die (6), successively and / or simultaneously, a composition comprising an alginate (A) and at least one composition comprising a polymer (B , C) different from said alginate (A).

14. Device (3) according to claim 12, characterized in that the extrusion means (4A, 4B, 5A, 5B, 7A, 7B, 8A, 8B) comprise first means (4A, 5A) adapted to pass under pressure said composition comprising an alginate (A) through the die (6), and at least second means (4B, 5B) able to pressurize said at least one composition comprising a polymer (B, C) different from said alginate (A) through the die (6).

15. Device (3) according to claim 12 or 13, characterized in that each of said first (4A, 5A) and at least second means (4B, 5B) comprises a jack (4A, 4B) and a syringe (5A, 5B). ).

16. Device (3) according to one of claims 12 to 14, characterized in that it comprises downstream of the extrusion die (6) a reservoir (9) containing a crosslinking agent, and a drying device (10) .

17. A method of manufacturing a heterogeneous filament (1) according to one of claims 1 to 8, characterized in that it comprises a step in which is passed, especially under pressure, through the same extrusion die (6), successively and / or simultaneously, a composition comprising an alginate (A) and at least one composition comprising a polymer (B, C) different from said alginate (A).