ITFI20120041A1 - NEW MULTIFUNCTIONAL SUTURE THREADS WITH RELEASE OF ANTIMICROBIAL, ANTIBIOTIC, CICATRIZING SUBSTANCES. - Google Patents

Description

PATENT APPLICATION FOR INDUSTRIAL INVENTION WITH THE TITLE:

NEW MULTIFUNCTIONAL SUTURE THREADS WITH CONTROLLED RELEASE

ANTIMICROBIAL, ANTIBIOTIC, HEALING SUBSTANCES

FIELD OF INVENTION

The present invention refers to the field of medical-surgical devices and in particular it refers to a method for producing suture threads with multifunctional properties (antimicrobial and / or antibiotic and / or cicatrizing); the preparation method foresees the incorporation of the antimicrobial and / or healing agent from the melt and the possibility of modulating the release of the quantity of antimicrobial and / or antibiotic and / or healing substance according to the preparation conditions.

STATE OF THE ART

Sutures are classified according to different criteria, which essentially concern the need to be removed, their structure or their composition.

Depending on the structure of the thread, the sutures can be braided or single-stranded. According to the composition, however, the suture can be natural or synthetic. According to their fate in contact with the living organism, the threads can be divided into two broad categories: absorbable and non-absorbable. The materials typically used for the production of non-absorbable yarns are: silk and linen as regards materials of natural origin, while nylon, polyester, polypropylene, polytetrafluoroethylene, polyvinylenfluoride are included among the synthetic materials of this type of yarn.

Polydioxanone, polyglycolic acid, polylactic acid, polycaprolactone and binary or ternary copolymers of the latter three polymers constitute the main polymeric materials used for the production of absorbable sutures. Furthermore, in some cases the polycaprolactone is used as a coating polymer of the yarn to increase properties such as smoothness.

The insertion of foreign material into the organism always triggers a more or less intense immune reaction. After implementation, the suture becomes covered with very protein-rich fluids such as fibrinogen and fibronectin, which create the perfect environment for bacterial proliferation. Once the suture is contaminated, the immune system triggers local disinfection systems, mostly mediated by granulocytes, which are ineffective and cause the onset of inflammatory reactions that can be more or less serious.

Therefore, the need arises to reinforce the body's defenses so that the bacterial colony can be eradicated. This can be done by taking drugs, such as antibiotics, which slow down or completely block microbial proliferation, or by giving the suture properties that make it immune to bacterial attacks.

Another important requirement that the suture threads must satisfy is to promote wound healing. The suture thread is used to keep the flaps of tissue close together, which must reconstitute a continuum in the shortest possible time. From this point of view, the presence of suitable healing agents is particularly useful.

In both cases described above, it is necessary to be able to modulate the release of the additives present in the yarn in order to ensure that the right amount of active substance is released in a desired time interval.

The production of threads with antimicrobial and / or antibiotic and / or healing properties is still the subject of studies. The greatest difficulty lies in finding a good compromise between yarn effectiveness and cost, an aspect that certainly should not be overlooked. If on the one hand the use of antimicrobial and / or antibiotic and / or cicatrizing threads would reduce (or completely eliminate) the costs of drugs to be taken during the post-operative period, on the other hand the production costs must be such to guarantee an affordable price.

The transfer of specific properties to the suture thread can be carried out through different methods and can modify the structure of the polymer or not. In both cases it must be checked that the introduction of the antimicrobial and / or antibiotic and / or healing agent does not significantly modify the mechanical properties of the material.

The antimicrobial must therefore be compatible with the polymer, and maintain its antiseptic properties for the entire period between the production of the yarn and its implementation.

Another aspect that should not be underestimated, as already highlighted, is the release speed of the substance. The optimal condition is that in which most of the antimicrobial and / or antibiotic and / or healing is released during the more delicate phase (about 10 days after using the thread) in which the wound is more easily attacked from bacteria and the scar tissue is not yet fully formed. It can therefore be understood how difficult it is to find a polymer-antimicrobial and / or antibiotic and / or healing agent coupling that satisfies all the required characteristics.

The methods currently used for the production of yarns with antibacterial properties are essentially three: coating, grafting and melt incorporation.

The coating consists of the physical coating of a material, which takes the name of substrate, through immersion in a fluid (often a solution) that contains the substance that is desired to be obtained on the surface. In this way the substrate will be covered by a thin film, the thickness of which depends on numerous factors including the viscosity of the solution, the extraction speed, the surface tension and the acceleration of gravity.

The process takes place in four steps:

â € ¢ Immersion: the substrate is immersed in the solution at a more or less constant speed, avoiding sudden movements;

â € ¢ Permanence in contact with the solution;

â € ¢ Extraction: the higher the speed with which the substrate is extracted, the greater the thickness of the film;

â € ¢ Drying and evaporation of the solvent.

In the literature there are several cases of preparing modified threads through the coating, in which the suture thread is immersed in a solution containing the active substance.

Grafting consists in the introduction of particular chemical groups on the surface of a polymer, in such a way as to give the material properties it did not have before. Grafting is usually carried out by introducing the polymer into a solution, in conditions of temperature and pH such as to favor the grafting of the desired functional groups into the polymer chain. The percentage of grafting can easily be controlled by varying the operating conditions.

Since the structure of the polymer is partially modified, it must be ensured that its mechanical characteristics are not compromised.

The melt incorporation consists in the addition of the antimicrobial substance during the extrusion operation. The polymer in the form of powder or granules is mixed in the solid state with the antimicrobial agent which preferably must be in the form of powder. The physical mixture thus obtained is introduced into the extruder through the loading hopper and extruded at a temperature profile and at a speed appropriate for the processing of the polymer used. The material thus prepared is fed, in a separate stage, to a spinning module in order to create the antimicrobial yarns.

All three methods are the subject of scientific studies reported in the literature, but the most widespread is the coating which, among other things, is the method by which the antibacterial sutures currently on the market are made.

Patent GB 2 410 028 describes an antimicrobial â € œmonofilamentâ € suitable as a test tool for diabetic neuropathies. Said monofilament is rigid. In particular, reference is made to the fact that this monofilament is not disposable and for this reason the antimicrobial and / or antifungal properties are useful to avoid contamination between one patient and another. It then generalizes on its use stating that it could be used for other applications such as bristles for toothbrushes, hairbrushes but also as sutures. The polymers indicated for the manufacture of said monofilament are PBT, PET and nylon; while the only example of a possible antimicrobial agent is Duraban <TM>. It should be noted that in the patent no particular reference is made to the method of preparation of the monofilament and in a very vague and generic way it refers to the incorporation of the antimicrobial agent which can be easily accepted in the polymers during extrusion but without any evidence on the actual realization of an artifact much less than a suture thread.

WO 0128601 describes the preparation of sutures with antimicrobial properties. This is accomplished through the preparation of a coating to be applied to the outer surface of the suture or the incorporation of an antimicrobial agent. But although the patent is very rich in details, no details are given on what is meant by incorporation and how it can be achieved. The antimicrobial agents to which the patent refers are water-soluble glasses that release metal ions such as silver, copper or zinc.

The patent n. EP 1157708 A2 has as its object the preparation of surgical devices, such as suture threads with antimicrobial properties made by incorporating an antimicrobial agent from the melt during the extrusion operation. In particular, however, the thread is not made in a single step but the material obtained by extrusion is granulated and used to feed a second extruder with which to produce the desired product such as a suture thread. Furthermore, the possibility of modulating the mechanical resistance and / or the release of the incorporated substance through the adjustment of the processing and post-processing parameters is not reported.

The patent n. WO 86/02561 reports a method for the preparation of plastic objects containing chlorhexidine by incorporating this substance from a melt into hydrophobic polymers such as polyethylene or polypropylene. Also in this case there is no reference to the possibility of modulating the quantity of substance released by varying the operating parameters of extrusion, spinning and drafting.

The purpose of the present invention is to provide a simplified and economically advantageous method for the preparation of sutures with controlled release of antimicrobial and / or antibiotic and / or healing agents.

SUMMARY OF THE INVENTION

1. The present invention solves the above problems by means of a method for the preparation of multifunctional sutures with controlled release of antimicrobial and / or antibiotic and / or cicatrizing substances, said method comprising the incorporation of one or more of said substances and said melt incorporation followed by an in-line spinning downstream of the extruder by drawing under certain drawing conditions such as to give said yarns a controlled release of the substances incorporated according to the following function:

Q = (aDR + b) c

where is it

Q is the quantity of agent released per surface unit;

where a and b are unique constants that depend on the polymer / additive pair;

2 2 <DR => DR is the stretching ratio: <D> 0 </D> f,

where D0à is the diameter of the extruder nozzle and Dfà is the final diameter of the fiber;

the antibiotic and / or healing and / or antimicrobial substances are incorporated by melt into polymers selected from those normally used for the production of sutures, both absorbable and non-absorbable;

polymer / additive combinations are identified on the basis of possible processing temperatures; in particular, the maximum temperature of the thermal profile must be at least 10 ° C above the melting temperature of the polymer and at least 10 ° C below its degradation temperature; moreover, this temperature must be at least 5 ° C lower than the melting temperature or the decomposition temperature of the additive to be incorporated if this is lower than the melting point.

Depending on the stretch conditions used, it is possible to modulate the final diameter reached, the mechanical strength but above all the release of the necessary quantity of substance, in space (i.e. locally near the filament) and over time (i.e. by adjusting the duration of the antibiotic and / or healing and / or antimicrobial action).

The aforesaid material is suitable for the preparation or coating of medical surgical devices; in particular it is suitable for the preparation of sutures with antimicrobial properties.

The present invention therefore relates to said suture threads characterized in that an antimicrobial and / or antibiotic and / or healing agent is incorporated by melt into a biocompatible polymeric material, selected from those known for the manufacture of sutures.

A further object of this invention are sutures obtainable with the process according to the invention, said threads having antimicrobial and / or antibiotic and / or healing properties, whose release can be modulated over time and space based on the ironing conditions with which they were produced

It results from the comparison with the methods described above that the method object of this invention introduces a wide range of improvements and advantages both on the preparation method and on the finished product. The first advantage of all is the simplicity of making the final product. In fact, through the spinning operation alone, and in a single stage, it is possible to provide the yarn with the properties described above. On the other hand, in the case of coating or grafting, a series of operations downstream of the spinning are necessary to provide the yarn with antibacterial properties. The reduction in the number of operations has an obvious advantage not only for saving production times but above all it avoids the use of other products and solvents other than the polymeric matrix and the antimicrobial agent. This has obvious positive implications from an environmental and economic point of view but also with regard to the safety of the modified wire. In fact, the use of solvents, foreseen by the other two methods, has the direct consequence of the need to dispose of these substances. Furthermore, during the use of the yarn there could be a release, obviously unwanted, of solvent residues present in the filament.

The incorporation of the antimicrobial and / or antibiotic and / or healing agent, in addition to conferring specific properties to the thread, can also act as a reinforcement, increasing the mechanical properties of the product. This result was unexpected given the notorious difficulty in finding a polymer-antimicrobial coupling that satisfies all the characteristics required for biomedical applications.

Furthermore, incorporating the antimicrobial agent rather than placing it only on the surface allows greater control in its release by appropriately modulating certain parameters such as:

â € ¢ the concentration of antimicrobial introduced,

â € ¢ process variables such as towing speed,

â € ¢ cold drawing of the yarns.

BRIEF DESCRIPTION OF THE FIGURES

Scheme. 1 - shows a diagram of the preparation method according to the invention by using an extruder with primary inlet and secondary inlets.

FIG. 1 - shows for PLC / CHX sutures prepared with the method of the invention the results regarding the release of antimicrobial substance as the incorporated concentration and the stretching conditions vary

FIG. 2 - SEM micrographs of PLC / CHX sutures prepared according to the method of the invention.

FIG. 3 - shows the results of antibacterial activity of PLC / CHX sutures prepared according to the method of the invention, said activity investigated by means of a diffusion test in agar against a positive Gram.

FIG.4 - graphically shows the linear law QCHX = mPCL / CHX · cCHX for the PLC / CHX pair.

FIG. 5 - graphically shows how the unique constants a and b for the PLC / CHX pair have been obtained.

FIG. 6 - shows for PP / CFX sutures prepared with the method of the invention the results regarding the release of antimicrobial substance as the incorporated concentration and the stretching conditions vary

FIG. 7 - SEM micrographs of PP / CFX sutures prepared according to the method of the invention.

FIG. 8 - shows the results of antibacterial activity of PP / CFX sutures prepared according to the method of the invention, said activity investigated by means of a diffusion test in agar against a positive Gram.

FIG.9 - graphically shows the linear law QCFX = mPP / CFX · cCFX for the PP / CFX pair.

FIG. 10 â € “graphically shows how the unique constants a and b for the PP / CFX pair have been obtained.

DETAILED DESCRIPTION OF THE INVENTION

The amount of agent released strongly depends on the concentration of this substance on the surface of the device. This surface concentration can be controlled and modulated both through the initial quantity incorporated during processing and, above all, by changing the draw ratio used during the production of the fibers. In fact, the surface concentration can be varied and controlled by changing the extension of the lateral surface on which it is distributed.

the agent. This lateral surface (<S = Ï € Df L f>, where Df is the diameter of the fiber and Lfla its length) depends on the stretching ratio applied according to a very precise law. In particular, to derive this relationship it is enough to remember the definition of <DR = A> stretching ratio: <0 / A f>, where A0 is the section of the extruder nozzle and Af is the final section of the fiber . Simplifying it appropriately, the stretching ratio can be rewritten as a function of the diameters according to the following expression:

2 2 <DR = D 0 / D f>, where D0 is the diameter of the extruder nozzle and Df is the end diameter of the fiber. So, ultimately, by varying the stretching ratio it is possible to modulate the surface concentration of the additive and therefore to modulate and control the quantity released.

The antibiotic and / or healing and / or antimicrobial activity directly depends on the quantity of agent released and this quantity can be controlled, as already said, by varying both the concentration of additive incorporated and the stretching ratio. This concept can be mathematically expressed through two functions that link the quantity of additive released to the concentration and the stretching ratio. In particular, the quantity of agent released per surface unit (Q) is linked to the concentration by weight of the incorporated substance c through a law of the type: Q = m c where m depends on the stretching ratio applied according to a law of type: <m = aDR b>, where a and b are unique constants that depend on the polymer / additive pair and DR is the stretching ratio.

Through this preparation method - which can be generalized to all the polymer / additive pairs as identified above - it is therefore possible to state that, once parameters a and b have been identified, it is possible to prepare yarns with full control of the quantity of additives released.

By antimicrobial or antibiotic substances suitable for the present invention we mean antibiotics, antibiotics, bacteriostats, bactericides and antiseptics that are organic molecules (small molecules), of natural or synthetic origin, approved for use as medicaments or as medical surgical devices ; the metal ions of silver, copper or zinc and their soluble glasses are excluded from the antimicrobial substances suitable for the present invention, and organosilanes such as 3- (trimethyloxysilyl) propyldimethyloctadecyl ammonium chloride are also excluded.

By healing substances suitable for the present invention we mean substances capable of accelerating the healing process of wounds, ulcers and burns by removing the residues of the inflammatory process and restoring the integrity of the skin structures. These substances of natural or synthetic origin must be approved for use as medicaments or as medical surgical aids

The polymers that can be used are all those normally used for the production of sutures, both absorbable and non-absorbable and listed above, i.e. they are preferably selected from polyamides (nylon), polyester, polypropylene, polytetrafluoroethylene, polyvinylidene fluoride, polydioxanone, polyglycolic acid, polylactic acid, polycaprolactone, binary or ternary copolymers of the latter three polymers as well as their mixtures.

The choice of the antimicrobial and / or antibiotic and / or healing substance is mainly related to the application for which it is intended, but also to the type of pathogen to be countered or to the location of the wound that must be healed as well as capable of withstanding, while remaining unaltered, the temperatures reached during incorporation from the melt.

For biomedical applications and in particular for sutures, the choice of the above substances is considerably reduced by the fact that the substance in question must not be toxic or have harmful side effects for the body. Furthermore, with regard to the protective action against bacterial attack, it must have activity against the microorganisms that usually attack a wound, such as Escherichia Coli, Staphylococcus Epidermidis and Staphylococcus Aureus, and must be compatible with the material that constitutes the thread. By way of example, antimicrobials such as chlorhexidine, neomycin, nalidixic acid, nisin and ciprofloxacin fall within the class of antimicrobials / antibiotics, although they are not the only ones.

Regarding the healing properties, substances such as hyaluronic acid, Triticum Vulgaris, collagen, catalase are included, by way of mere example, although they are not the only ones.

The additive (antibiotic and / or healing and / or antimicrobial) can be either in the form of powder or liquid. It is fed through one of the secondary loading hoppers, located at a defined distance from the main one, in order to include the substance in the already melted polymer (fed to the extruder via the main loading hopper) in an appropriate way and measure at the same time the residence time inside the extruder and therefore also the final properties of the device (diagram 1).

The mixture is extruded at a temperature profile (generally in the range 70 ° C - 300 ° C) and at a speed (depending on the flow rate to be produced and the residence time in general in the range of 20 sec. -10 min .) suitable for processing the polymeric material of which the device is made. The polymer / additive pairs are identified on the basis of the possible processing temperatures. In particular, the maximum temperature of the thermal profile must be at least 10 ° C above the melting temperature of the polymer and at least 10 ° C below its degradation temperature. Furthermore, this temperature must be at least 5 ° C lower than the melting temperature or the decomposition temperature of the additive to be incorporated (antibiotic and / or healing and / or antimicrobial), if this is lower than that of merger.

Downstream of the extruder, an in-line spinning system allows the direct preparation of the yarns that are stretched in isothermal or non-isothermal conditions, modulating the final diameter reached, the mechanical strength but above all the release of the necessary quantity through the stretch conditions used. of substance, in space (ie locally near the filament) and in time (ie by regulating the duration of the antibiotic and / or healing and / or antimicrobial action). The antimicrobial action of the thread is exerted through migration and the consequent release of the active agent. It is therefore possible to modulate the duration of the release also by appropriately choosing the concentration of antimicrobial agent to be incorporated as well as modifying the structure of the polymeric matrix in an appropriate manner.

The present invention can be better understood in the light of the following embodiment examples.

EXPERIMENTAL PART

EXAMPLE 1:

The method just described was applied as an example for the preparation of sutures made of polycaprolactone (PCL) and in which the substance incorporated was an antimicrobial agent, chlorhexidine diacetate (CHX).

Both the chlorhexidine (in the form of diacetate) and the PCL used in this work are two commercial samples supplied by Sigma Aldrich.

The polymer, in the form of granules, was introduced into the main loading hopper of a co-rotating twin-screw extruder, while the antimicrobial agent, in the form of powder, was fed through a secondary loading hopper. The mixture was extruded at a temperature profile of 40-50-70-100 ° C through a cylindrical nozzle with a diameter of 1 mm. At the exit of the extruder the wires were cooled and at the same time stretched through a pulling system until the desired diameter was obtained. Three draw ratios were used: DR = 11, DR = 25 and DR = 44, obtaining fibers with final diameters of 300 µm, 200 µm and 150 µm respectively. Threads containing different concentrations by weight of chlorhexidine, 1%, 2% and 4%, were produced.

The control of the antibacterial activity of the threads produced was investigated through diffusion tests in agar. The inhibition of both Gram positive (M. luteus, and B. subtilis) and one Gram negative (E. coli) was investigated by evaluating the zone of inhibition around the fibers. Bacterial growth inhibition tests in liquid medium were also conducted.

The release of CHX from the fibers in distilled water was evaluated with a UV-vis Shimatzu spectrophotometer.

The different concentrations used but above all the different stretching ratios made it possible to modulate the release of the incorporated substance both in terms of quantity and duration as is evident from figure 1.

The SEM micrographs of figure 2 a-b confirm that the quantity of CHX released strongly depends on the concentration of this substance on the surface of the device. In particular, the yarn drawn at DR = 11 (figure 2a) has a greater quantity of CHX on the surface than the one with DR = 44 (figure 2b).

The antibacterial activity of the prepared threads is closely related to the release of the incorporated substance and therefore by modulating this release it was also possible to modulate the antibacterial action of the threads as shown in figure 3 where the results of the inhibition test against a positive Gram (M. luteus) of both groups of threads produced.

It is evident that all the strands containing chlorhexidine show a clear halo of inhibition. On the contrary, however, the yarn made up of the pure polymer does not show any antibacterial activity. It is equally evident that the halo of inhibition is lower in the case of yarns produced with a higher draw ratio. A comparable result was also obtained in the case of the Gram negative test.

The antibacterial efficacy of the prepared threads was also evaluated through inhibition tests in a liquid medium. These tests also confirmed the clear antibacterial activity carried out by the threads containing chlorhexidine.

The antimicrobial activity directly depends on the quantity of antimicrobial released and this quantity can be controlled, as already said, by varying both the concentration of CHX incorporated and the stretching ratio. In fact, what was previously said in the general case is verified in the specific example reported. In particular, the quantity of CHX released per surface unit (QCHX) follows a linear law of the type: QCHX = mPCL / CHX (figure 4.) mPCL / CHX can be obtained from

following reads: <mPCL / CHX = aPCL / CHXDR bPCL / CHX>, where a and b are constants that for the PCL / CHX system are respectively - 0.037 and 2.3123 (figure 5).

EXAMPLE 2:

The method was also applied for the preparation of sutures made of polypropylene (PP) and in which the substance incorporated was an antibiotic agent, ciprofloxacin (CFX).

The ciprofloxacin and polypropylene used in this work are two commercial samples supplied by Sigma Aldrich and Basell respectively.

The polymer, in the form of granules, was introduced into the main loading hopper of a co-rotating twin-screw extruder, while the antibiotic agent, in the form of powder, was fed through a secondary loading hopper. The mixture was extruded at a temperature profile of 130-160-180-200 ° C through a cylindrical nozzle with a diameter of 1 mm. At the exit of the extruder the wires were cooled and at the same time stretched through a pulling system until the desired diameter was obtained. Three draw ratios were used: DR = 4, DR = 14 and DR = 39, respectively obtaining fibers with final diameters equal to, respectively, 500 µm, 270 µm and 160 µm. Threads containing different concentrations by weight of ciprofloxacin, 1%, 2% and 4%, were produced.

The control of the antibacterial activity of the threads produced was investigated through diffusion tests in agar. The inhibition of both Gram positive (M. luteus, and B. subtilis) and one Gram negative (E. coli) was investigated by evaluating the zone of inhibition around the fibers. Bacterial growth inhibition tests in liquid medium were also conducted.

The release of CFX from the fibers in distilled water was evaluated with a UV-vis Shimatzu spectrophotometer.

The different concentrations used but above all the different stretching ratios made it possible to modulate the release of the incorporated substance both in terms of quantity and duration as can be seen from figure 6.

The SEM micrographs of figure 7 a-b confirm that the quantity of CFX released strongly depends on the concentration of this substance on the surface of the device. In particular, the yarn drawn at DR = 4 (figure 2a) has a greater quantity of CFX on the surface than the one with DR = 39 (figure 2b).

The antibacterial activity of the prepared threads is closely related to the release of the incorporated substance and therefore by modulating this release it was also possible to modulate the antibacterial action of the threads as shown in figure 8 where the results of the inhibition test against a positive Gram (M. luteus) of both groups of threads produced.

It is evident that all strands containing ciprofloxacin show a clear halo of inhibition. On the contrary, however, the yarn made up of the pure polymer does not show any antibacterial activity. It is equally evident that the halo of inhibition is lower in the case of yarns produced with a higher draw ratio. A comparable result was also obtained in the case of the Gram negative test.

The antibacterial efficacy of the prepared threads was also evaluated through inhibition tests in a liquid medium. These tests also confirmed the clear antibacterial activity carried out by the threads containing ciprofloxacin.

The antibacterial activity directly depends on the quantity of antimicrobial released and this quantity can be controlled, as already said, by varying both the concentration of CHX incorporated and the stretching ratio. In fact, what was previously said in the general case is verified in the specific example reported. In particular, the quantity of CFX released per surface unit (QCFX) follows a linear law of the type: QCFX = mPP / CFX (figure 9). mPP / CFX can be obtained from the following law: mPP / CFX = aPP / CFXDR bPP / CFX, where a and b are constants which for the PP / CFX system are respectively - 0.0014 and 0.0923 (figure 10).

Claims (5)

CLAIMS 1. A method for the production of multifunctional sutures with controlled release of antimicrobial and / or antibiotic and / or healing substances, said method comprising the incorporation from the melt of one or more of said substances and said incorporation from the melt followed by an in-line spinning downstream of the extruder by drawing under certain drawing conditions such as to give said yarns a controlled release of the substances incorporated according to the following function: Q = (aDR + b) c where is it Q is the quantity of agent released per surface unit; where a and b are unique constants that depend on the polymer / additive pair; 2 2 <DR = D> DR is the stretching ratio: 0 </D> f, where D0à is the diameter of the extruder nozzle and Dfà is the final diameter of the fiber; the antibiotic and / or healing and / or antimicrobial substances are incorporated by melt into polymers selected from those normally used for the production of sutures, both absorbable and non-absorbable; the polymer / additive combinations are identified on the basis of the possible processing temperatures; in particular, the maximum temperature of the thermal profile must be at least 10 ° C above the melting temperature of the polymer and at least 10 ° C below its degradation temperature; furthermore, this temperature must be at least 5 ° C lower than the melting temperature or the decomposition temperature of the additive to be incorporated if this is lower than the melting point. 2. Method according to claim 1 in which the additive is selected from among which antimicrobials such as chlorhexidine, neomycin or nalidixic acid, antibiotics such as ciprofloxacin and cicatrisants such as Triticum vulgaris or hyaluronic acid, collagen, catalase. Method according to any one of claims 1-2, wherein the polymer is selected from nylon, polyester, polypropylene, polytetrafluoroethylene, polyvinylenfluoride, polydioxanone, polyglycolic acid, polylactic acid, polycaprolactone and binary or ternary copolymers of the latter three polymers. 4. Method according to claims 2 and 3 in which the additive is selected from chlorexedine and ciprofloxacin, and the polymer is selected from polypropylene and polycaprolactone. 5. Multifunctional sutures with controlled release of antimicrobial and / or antibiotic and / or healing substances, obtainable from the process according to any one of claims 1-4, in which the controlled release of the incorporated substances is according to the following function: Q = (aDR + b) c where is it Q is the quantity of agent released per surface unit; where a and b are unique constants that depend on the polymer / additive pair; 2 2 <DR D> DR is the stretching ratio: <=> 0 </D> f, where D0à is the diameter of the extruder nozzle and Dfà is the final diameter of the fiber; in which the antibiotic and / or healing and / or antimicrobial substances have been incorporated by melt into polymers selected from those normally used for the production of sutures, both absorbable and non-absorbable.