Polymer antibacterial coatings for polypropylene surgical sutures and mesh endoprostheses

Abstract

The present invention is directed to an antibacterial coating for surgical sutures and mesh endoprostheses comprising polypropylene, whereby the antibacterial coating comprises: a) an adhesive layer comprising poly-ε-caprolactone; b) an intermediate layer comprising poly-ε-caprolactone and micro- containers of poly-ε-caprolactone, whereby these microcontainers are loaded with a first antibacterial drug; and c) an outer layer comprising poly(L-lactic acid) and poly(lactic-co-glycolic acid) and a second antibacterial drug. This antibacterial coating provides multimodal antibacterial drug release. The present invention is further directed to a surgical suture or a mesh endoprosthesis comprising polypropylene, whereby the surgical suture or mesh endoprosthesis comprises such an antibacterial coating, as well as to a process for its manufacture. The first antibacterial drug is preferably an aminoglycoside such as e.g. gentamicin sulfate and the second antibacterial drug is preferably a tetracycline such as e.g. minocycline hydrochloride.

Description

[0001] Claims

[0002] 1 . An antibacterial coating for surgical sutures and mesh endoprostheses comprising polypropylene, whereby the antibacterial coating comprises: a) an adhesive layer comprising poly-s-caprolactone; b) an intermediate layer comprising poly-s-caprolactone and microcontainers of poly-s-caprolactone, whereby these microcontainers are loaded with a first antibacterial drug; and c) an outer layer comprising poly(L-lactic acid) and poly(lactic-co- glycolic acid) and a second antibacterial drug.

[0003] 2. The antibacterial coating according to claim 1 , whereby the adhesive layer and / or the intermediate layer independently from each other comprise poly-s-caprolactone with a mass average molar mass in the range of from 15 to 145 kDa, preferably with a mass average molar mass in the range of from 60 to 100 kDa, more preferably with a mass average molar mass in the range of from 70 to 90 kDa, even more preferably with a mass average molar mass in the range of from 75 to 85 kDa, most preferably with a mass average molar mass of 80 kDa.

[0004] 3. The antibacterial coating according to claim 1 and / or claim 2, whereby in the inner layer the amount of the first antibacterial drug packaged in the microcontainers of poly-s-caprolactone is in the range of from 0.02 to 0.45 mg / cm2, preferably it is in the range of from 0.09 to 0.41 mg / cm2, more preferably it is in the range of from 0.12 to 0.38 mg / cm2, even more preferably it is in the range of from 0.18 to 0.33 mg / cm2, most preferably it is in the range of from 0.22 to 0.29 mg / cm2, all amounts based on the surface of the inner layer in cm2. The antibacterial coating according to any one or more of claims 1 to 3, whereby the amount of the poly-s-ca prolactone in the adhesive layer and / or the intermediate layer is at least 90 weight-%, preferably at least 92 weight-%, more preferably at least 95 weight- %, even more preferably at least 99 weight-%, most preferably at least 99.9 weight-%, based on the total weight of the adhesive layer and the intermediate layer, respectively. The antibacterial coating according to any one or more of claims

[0005] 1 to 4, whereby the total amount of poly(L-lactic acid) and poly(lactic-co-glycolic acid) in the outer layer is at least 90 weight- %, preferably at least 92 weight-%, more preferably at least 95 weight-%, even more preferably at least 99 weight-%, most preferably at least 99.9 weight-%, based on the total weight of the outer layer. The antibacterial coating according to any one or more of claims 1 to 5, whereby the weight ratio of the poly(L-lactic acid) to the poly(lactic-co-glycolic acid) in the outer layer is in a range of from 0.5 : 10 to 10 : 10, preferably it is in a range of from 1 : 10 to 5 : 10, more preferably it is in a range of from 2 : 10 to 4 : 10, even more preferably it is in a range of from 2.5 : 10 to 3.5 : 10, most preferably it is 3 : 10. The antibacterial coating according to any one or more of claims 1 to 6, whereby the poly(L-lactic acid) used for the outer layer has a mass average molar mass in the range of from 35 to 105 kDa, preferably a mass average molar mass in the range of from 45 to 95 kDa, more preferably a mass average molar mass in the range of from 55 fo 85 kDo, even more preferably a mass average molar mass in the range of from 65 to 75 kDa, most preferably a mass average molar mass of 70 kDa. . The antibacterial coating according to any one or more of claims

[0006] 1 to 7, whereby the poly(lactic-co-glycolic acid) used for the outer layer has a mass average molar mass in the range of from 5 to 90 kDa, preferably a mass average molar mass in the range of from 10 to 80 kDa, more preferably a mass average molar mass in the range of from 20 to 70 kDa, even more preferably a mass average molar mass in the range of from 25 to 65 kDa, most preferably a mass average molar mass in the range of from 30 to 60 kDa. . The antibacterial coating according to any one or more of claims

[0007] 1 to 8, whereby the molar ratio of lactic acid, preferably of L-lactic acid, to glycolic acid in poly(lactic-co-glycolic acid) is in the range of from 1 : 5 to 5 : 1 , more preferably in the range of from 1 : 3 to 3 : 1 , even more preferably in the range of from 1 : 2 to 2 : 1 , most preferably it is 1 : 1 .

[0008] 10. The antibacterial coating according to any one or more of claims

[0009] 1 to 9, whereby the amount of the second antibacterial drug in the outer layer is in the range of from 1 to 5 mg / cm2, preferably it is in the range of from 1 .5 to 4 mg / cm2, more preferably it is in the range of from 2.1 to 3.5 mg / cm2, even more preferably it is in the range of from 2.3 to 3.3 mg / cm2, most preferably it is in the range of from 2.6 to 3 mg / cm2.

[0010] 1 1 .The antibacterial coating according to any one or more of claims

[0011] 1 to 10, whereby the first antibacterial drug and / or the second antibacterial drug are independently selected from each other from at least a drug being active against gram-negative bacteria and / or gram-positive bacteria, preferably whereby the first antibacterial drug and / or the second antibacterial drug are independently selected from each other from a drug being active against at least one of the following bacteria: Pseudomonas, Proteus, Escherichia coll, Klebsiella pneumoniae, Enterobacter aerogenes, Serratia and Staphylococcus, more preferably whereby the first antibacterial drug and / or the second antibacterial drug are independently selected from each other from gentamicin, neomycin, streptomycin, ampicillin, chlorhexidine, rifampicin, vamcomy- cin, ofloxacin, tetracycline, ciproflaxin and minocycline as well as any of their pharmaceutically acceptable salts and any mixtures thereof, even more preferably whereby the first antibacterial drug and / or the second antibacterial drug are independently selected from each other from gentamicin, neomycin, streptomycin and minocycline as well as any of their pharmaceutically acceptable salts and any mixtures thereof, most preferably whereby the first antibacterial drug is gentamicin sulfate and / or any other pharmaceutically acceptable salt of gentamicin and the second antibacterial drug is minocycline hydrochloride and / or any other pharmaceutically acceptable salt of minocycline hydrochloride.

[0012] 12. The antibacterial coating according to any one or more of claims

[0013] 1 to 1 1 , whereby the antibacterial coating comprises: a) an adhesive layer comprising poly-s-caprolactone in an amount of at least 99 weight-%, based on the total weight of the adhesive layer, whereby the poly-s-caprolactone has a mass average molar mass in the range of from 75 to 85 kDa; b) an intermediate layer comprising poly-s-caprolactone in an amount of at least 99 weight-%, based on the total weight of the intermediate layer, and microcontainers of poly-s-ca prolactone, whereby these microcontainers are loaded with gentamicin sulfate and / or any other pharmaceutically acceptable salt of gentamicin, whereby the poly-s-caprolactone has a mass average molar mass in the range of from 75 to 85 kDa; c) an outer layer comprising poly(L-lactic acid) and poly(lactic-co- glycolic acid) and minocycline hydrochloride and / or any other pharmaceutically acceptable salt of minocycline; whereby the total amount of poly(L-lactic acid) and poly(lactic-co-glycolic acid) in the outer layer is at least 99 weight-%, based on the total weight of the outer layer; whereby the weight ratio of the poly(L-lactic acid) to the poly(lactic-co-glycolic acid) in the outer layer is in a range of from 2.5 : 10 to 3.5 : 10; whereby the poly(L-lactic acid) has a mass average molar mass in the range of from 65 to 75 kDa; whereby the poly(lactic-co-glycolic acid) has a mass average molar mass in the range of from 25 to 65 kDa; and whereby the molar ratio of lactic acid, preferably of L-lactic acid, to glycolic acid in poly(lactic-co-glycolic acid) is in the range of from 1 : 2 to 2 : 1 .

[0014] 13. A surgical suture or a mesh endoprosthesis comprising polypropylene, whereby the surgical suture or mesh endoprosthesis comprises an antibacterial coating according to any one or more of claims 1 to 12.

[0015] 14. A process for the manufacture of a surgical suture or a mesh endoprosthesis according to claim 13, comprising the following steps: i) providing a surgical suture or mesh endoprosthesis comprising polypropylene; ii) providing a first solution comprising poly-s-caprolactone, especially with one or more of the preferences as given above in a concentration in the range of from 1 to 4 weight-%, based on the total weight of the first solution, in a first organic solvent to obtain a first solution; iii) immersing the surgical suture or mesh endoprosthesis comprising polypropylene into the first solution provided in step ii), removing and drying it to obtain a surgical suture or mesh endoprosthesis comprising polypropylene with an adhesive layer comprising poly-s-caprolactone; iv) providing an aqeuous solution comprising microcontainers comprising poly-s-caprolactone, whereby the microcontainers are loaded with a first antibacterial drug; v) immersing the surgical suture or mesh endoprosthesis comprising polypropylene with the adhesive layer comprising poly-s- caprolactone obtained in step iii) into the aqueous solution of step iv), removing and drying it to obtain the surgical suture or mesh endoprosthesis further comprising an intermediate layer of microcontainers comprising poly-s-caprolactone, whereby the microcontainers are loaded with the first antibacterial drug; vi) providing a second solution comprising poly(L-lactic acid) and poly(lactic-co-glycolic acid) with one or more of their preferences as given above and a second antibacterial drug in a second organic solvent, whereby the concentration of poly ( L- lactic acid) in said second organic solvent is in the range of from 3 to 5 weight-%; whereby the concentration of poly(lactic- co-glycolic acid) in said second organic solvent is in the range of from 8 to 12 weight-%, and whereby the concentration of the second antibacterial drug in said second organic solvent is in the range of from 2 to 4 mg / ml, all amounts based on the total weight of the second solution; vii) immersing the surgical suture or mesh endoprosthesis comprising polypropylene with the adhesive layer comprising poly-e- caprolactone obtained in step iii) and the intermediate layer of microcontainers comprising poly-s-caprolactone, whereby the microcontainers are loaded with the first antibacterial drug, obtained in step v) into the second solution obtained in step vi), removing and drying it to obtain the surgical suture or the mesh endoprosthesis according to claim 13.

[0016] 15. The process according to claim 14, whereby the first organic solvent used in step ii) is a linear C1-4 alkanol or a branched C3-6 alkanol or any mixture thereof, preferably whereby the first organic solvent used in step ii) is isopropanol, methanol or ethanol or any mixture thereof, more preferably whereby the first organic solvent used in step ii) is ethanol or isopropanol, most preferably whereby the first organic solvent used in step ii) is ethanol; and / or whereby the second organic solvent used in step vi) is a linear C1-4 alkanol or a branched C3-6 alkanol or an ester of a C1-4 alkanoic acid with a linear C1-4 alkanol or a C3-6 ketone or an halogenated C1-2 hydrocarbon and any mixture thereof, preferably whereby the second organic solvent used in step vi) is methanol, ethyl acetate, acetone or chloroform or any mixture thereof, more preferably whereby the second organic solvent used in step vi) is a mixture of methanol and ethyl acetate, most preferably whereby the second organic solvent used in step vi) is a mixture of methanol and ethyl acetate with a volume ratio of 2 : 3. with a concentration of 1 mg / ml in the final solution, followed by evaporation of the water at 40oC for 3 days. To make the coating more elastic, glycerin was added to the polymer and antibiotic solution. The implant was tested clinically on one patient after the removal of an abdominal hernia. Exudate was collected through vacuum drainage, and its examination showed that bacterial sterility remained for 5 days. However, it is not clear how this indicator changed with the consequent rehabilitation of the patient.

[0017] In summary, we can conclude that at present there is still a need to create and optimise antibacterial coatings for PP-based surgical sutures and mesh endoprostheses that show a sufficiently long period of action. In addition, a multimodal antimicrobial drug release is also desired where an initial dose of antibiotic is released immediately (within a few days) followed by a slow and constant drug release (within weeks / months).

[0018] Summary of the invention

[0019] These needs are fulfilled by the present invention which is directed to an antibacterial coating for surgical sutures and mesh endoprostheses comprising polypropylene, whereby the antibacterial coating comprises: a) an adhesive layer comprising poly-s-ca prolactone; b) an intermediate layer comprising poly-s-ca prolactone and microcontainers of poly-s-caprolactone, whereby these microcontainers are loaded with a first antibacterial drug; and c) an outer layer comprising poly(L-lactic acid) and poly(lactic-co- glycolic acid) and a second antibacterial drug. This leads to a reduction of postoperative complications, primarily related to bacterial infection, inflammation and delayed regeneration of damaged tissues.

[0020] The antibacterial coatings according to the present invention show multimodal drug elution kinetics and prolonged antimicrobial action, especially when used on polypropylene surgical sutures and polypropylene mesh endoprostheses.

[0021] The main technical result of the invention is a long-term antibiotic release with mixed kinetics: fast exponential and slow constant, from the coated PP threads. The result is achieved by the formation of composite coatings on PP threads containing encapsulated and nonencapsulated fractions of antibiotic, e.g. minocycline, infused into polymer matrices.

[0022] The surgical sutures and mesh endoprostheses according to the present invention show a slow release of the one antibacterial drug (e.g. and preferably being minocycline hydrochloride) being non-linearly dependent on time in a total amount in the range of from 1 .9 to 3.5 mg / cm2, preferably in an amount in the range of from 2.2 to 3.2 mg / cm2, more preferably in an amount in the range of from 2.5 to 2.9 mg / cm2, during a period of up to about three weeks (0-21 days).

[0023] The surgical sutures and mesh endoprostheses according to the present invention show a release of the other antibacterial drug (e.g. and preferably being gentamicin sulfate) being non-linearly dependent on time in a total amount in the range of from 0.05 to 0.45 mg / cm2, preferably in an amount in the range of from 0.15 to 0.33 mg / cm2, more preferably in an amount in the range of from 0.22 to 0.26 mg / cm2, during a period of up to about 32 days (8 - 40 days). They show preferably at the same time especially a fast release of both antibacterial drugs (e.g. and preferably being minocycline hydrochloride and gentamicin sulfate) starting from an amount in the range of from 1 .4 to 3.7 mg / cm2, preferably from an amount in the range of from 1 .9 to 3.2 mg / cm2, more preferably from an amount in the range of from 2.4 to 2.7 mg / cm2, during a period of up to 14 days (0 - 14 days) up to a released amount in the range of from 0.25 to 0.50 mg / cm2, preferably in the range of from 0.30 to 0.45 mg / cm2, more preferably in the range of from 0.34 to 0.4 mg / cm2after said period (15 - 40 days) .

[0024] Detailed description of the invention

[0025] The present invention is directed to an antibacterial coating for surgical sutures and mesh endoprostheses comprising polypropylene, whereby the antibacterial coating comprises: a) an adhesive layer comprising poly-s-ca prolactone; b) an intermediate layer comprising poly-s-ca prolactone and microcontainers of poly-s-caprolactone, whereby these microcontainers are loaded with a first antibacterial drug; and c) an outer layer comprising poly(L-lactic acid) and poly(lactic-co- glycolic acid) and a second antibacterial drug.

[0026] The polymers used for the different layers of the antibacterial coating are described in greater detail below.

[0027] The adhesive layer and / or the intermediate layer comprise independently from each other especially poly-e-caprolactone with a mass average molar mass (“Mw”) in the range of from 15 to 145 kDa, preferably with a mass average molar mass in the range of from 60 to 100 kDa, more preferably with a mass average molar mass in the range of from 70 to 90 kDo, even more preferably with a mass average molar mass in the range of from 75 to 85 kDa, most preferably with a mass average molar mass of 80 kDa.

[0028] The poly-E-caprolactone mass average molar mass (“Mw”) is determined by gel permeation chromatography (GPC), a type of size exclusion chromatography (SEC), using Nexera GPC System (Shimadzu, Japan) and GPC -80 M mixed gel type column (Shimadzu, Japan) following the manufacturer’s protocol.

[0029] The amount of the poly-s-caprolactone in the adhesive layer and / or the intermediate layer is especially at least 90 weight-%, preferably at least 92 weight-%, more preferably at least 95 weight-%, even more preferably at least 99 weight-%, most preferably at least 99.9 weight-%, based on the total weight of the adhesive layer and the intermediate layer, respectively.

[0030] The microcontainers of poly-s-caprolactone comprise each the first antibacterial drug especially in an amount in the range of from 0.1 ■ 10-9to 10 - 10-9mg per microcontainer, preferably in an amount in the range of from 0.5- 10-9to 7- 10-9mg per microcontainer, more preferably in an amount in the range of from 1 ■ 10-9to 5- 10-9mg per microcontainer, even more preferably in an amount in the range of from 2.5- 10-9to 3.3- 10-9mg per microcontainer, most preferably in an amount in the range of from 2.7- 10-9to 3.1 - IO-9mg per microcontainer.

[0031] The amount of the microcontainers in the inner layer is especially in the range of from 1 ■ 106to 180- 106microcontainers / cm2, preferably it is in the range of from 20 ■ 106to 160 ■ 106microcontainers / cm2, more preferably it is in the range of from 40- 106to 140- 106microcontainers / cm2, even more preferably it is in the range of from 60- 106to 120- 106 microcontainers / cm2, most preferably it is in the range of from 80- 106to 100- 106microcontainers / cm2.

[0032] The amount of the first antibacterial drug in the inner layer is especially in the range of from 0.02 to 0.45 mg / cm2, preferably it is in the range of from 0.09 to 0.41 mg / cm2, more preferably it is in the range of from 0.12 to 0.38 mg / cm2, even more preferably it is in the range of from 0.18 to 0.33 mg / cm2, most preferably it is in the range of from 0.22 to 0.29 mg / cm2.

[0033] The poly(L-lactic acid) used for the outer layer has especially a mass average molar mass in the range of from 35 to 105 kDa, preferably a mass average molar mass in the range of from 45 to 95 kDa, more preferably a mass average molar mass in the range of from 55 to 85 kDa, even more preferably a mass average molar mass in the range of from 65 to 75 kDa, most preferably a mass average molar mass of 70 kDa.

[0034] The amount of the antibiotics in the coating and their in vitro release is determined with a high-performance liquid chromatography (HPLC) method using a UV-VIS detector. The analysis is preferably performed on a Shimadzu LC-6a high-performance liquid chromatograph (Shimadzu Corporation, Japan). A Zorbax Rx-C-18 col-umn (2,1 * 150 mm, 5 m) (Agilent, Germany) is preferably used for the separation. In that case, the column temperature is 30°C, the injection volume is 15 pl, and the flow rate is 0,7 ml / min. Minocycline hydrochloride and gentamicin sulfate are recorded using a UV-VIS detector at wavelengths of 273 and 286 nm respectively, with retention times of 2,8±0,l min and 6,6±0,l min, respectively.

[0035] The poly(lactic-co-glycolic acid) used for the outer layer has especially a mass average molar mass in the range of from 5 to 90 kDa, preferably a mass average molar mass in the range of from 10 to 80 kDa, more preferably a mass average molar mass in the range of from 20 to 70 kDa, even more preferably a mass average molar mass in the range of from 25 to 65 kDa, most preferably a mass average molar mass in the range of from 30 to 60 kDa.

[0036] The mass average molar masses of the poly(L-lactic acid) and poly(lactic-co-glycolic acid) are determined with gel permeation chromatography (GPC).

[0037] The molar ratio of lactic acid, preferably of L-lactic acid, to glycolic acid in poly(lactic-co-glycolic acid) is advantageously in the range of from 1 : 5 to 5 : 1 , more preferably in the range of from 1 : 3 to 3 : 1 , even more preferably in the range of from 1 : 2 to 2 : 1 , most preferably it is 1 : 1 .

[0038] The weight ratio of the poly(L-lactic acid) to the poly(lactic-co- glycolic acid) in the outer layer is especially in a range of from 0.5 : 10 to 10 : 10, preferably it is in a range of from 1 : 10 to 5 : 10, more preferably it is in a range of from 2 : 10 to 4 : 10, even more preferably it is in a range of from 2.5 : 10 to 3.5 : 10, most preferably it is 3 : 10.

[0039] The total amount of poly(L-lactic acid) and poly(lactic-co-gly- colic acid) in the outer layer is especially at least 90 weight-%, preferably at least 92 weight-%, more preferably at least 95 weight-%, even more preferably at least 99 weight-%, most preferably at least 99.9 weight-%, based on the total weight of the outer layer.

[0040] The amount of the second antibacterial drug in the outer layer is especially in the range of from 1 to 5 mg / cm2, preferably it is in the range of from 1 .5 to 4 mg / cm2, more preferably it is in the range of from 2.1 to 3.5 mg / cm2, even more preferably it is in the range of from 2.3 to 3.3 mg / cm2, most preferably it is in the range of from 2.6 to 3 mg / cm2. The first and the second antibacterial drug may be the same antibacterial drug or they may be different from each other. If only one antibacterial drug is used, it is preferably chosen from the class of tetracyclines.

[0041] In a preferred embodiment of the present invention the two antibacterial drugs are different from each other. In a further preferred embodiment of the present invention one antibacterial drug is chosen from the class of tetracyclines such as e.g. minocyline hydrochloride and / or any other pharmaceutically acceptable salt thereof and the other antibacterial drug is chosen from the class of aminoglycosides such as e.g. gentamicin sulfate and / or any other pharmaceutically acceptable salt thereof.

[0042] The first antibacterial drug and / or the second antibacterial drug are especially independently selected from each other from at least a drug being active against gram-negative bacteria and / or grampositive bacteria. Preferably the first antibacterial drug and / or the second antibacterial drug are independently selected from each other from a drug being active against at least one of the following bacteria: Pseudomonas, Proteus, Escherichia coli, Klebsiella pneumoniae, Entero- bacter aerogenes, Serratia and Staphylococcus, more preferably the first antibacterial drug and / or the second antibacterial drug are independently selected from each other from gentamicin, neomycin, streptomycin, ampicillin, chlorhexidine, rifampicin, vamcomycin, ofloxacin, tetracycline, ciproflaxin and minocycline as well as any of their pharmaceutically acceptable salts and any mixtures thereof, even more preferably the first antibacterial drug and / or the second antibacterial drug are independently selected from each other from gentamicin, neomycin, streptomycin and minocycline as well as any of their pharmaceutically acceptable salts and any mixtures thereof, most preferably the first antibacterial drug is gentamicin sulfate and / or any other pharmaceutically acceptable salt of gentamicin and the second antibacterial drug is minocycline hydrochloride and / or any other pharmaceutically acceptable salt of minocycline hydrochloride.

[0043] It is especially advantageous if two different classes of antibiotics are used, preferably if one antibiotic of the class of aminoglycosides and one antibiotic of the class of tetracyclines is used.

[0044] Another object of the present invention is a surgical suture or a mesh endoprosthesis comprising polypropylene, whereby the surgical suture or mesh endoprosthesis comprises an antibacterial coating as described above.

[0045] A further object of the present invention is a process for the manufacture of such a surgical suture or a mesh endoprosthesis comprising polypropylene, whereby the surgical suture or mesh endoprosthesis comprises an antibacterial coating with the preferences as described above. This process comprises the following steps: i) providing a surgical suture or mesh endoprosthesis comprising polypropylene; ii) providing a first solution comprising poly-s-caprolactone, especially with one or more of the preferences as given above in a concentration in the range of from 1 to 4 weight-%, based on the total weight of the first solution, in a first organic solvent to obtain a first solution; iii) immersing the surgical suture or mesh endoprosthesis comprising polypropylene into the first solution provided in step ii), removing and drying it to obtain a surgical suture or mesh endoprosthesis comprising polypropylene with on adhesive layer comprising poly-s-caprolactone; iv) providing an aqueous solution comprising microcontainers comprising poly-s-ca prolactone, whereby the microcontainers are loaded with a first antibacterial drug; v) immersing the surgical suture or mesh endoprosthesis comprising polypropylene with the adhesive layer comprising poly-s- caprolactone obtained in step iii) into the aqueous solution of step iv), removing and drying it to obtain the surgical suture or mesh endoprosthesis further comprising an intermediate layer of microcontainers comprising poly-s-caprolactone, whereby the microcontainers are loaded with the first antibacterial drug; vi) providing a second solution comprising poly(L-lactic acid) and poly(lactic-co-glycolic acid) with one or more of their preferences as given above and a second antibacterial drug in a second organic solvent, whereby the concentration of poly(L- lactic acid) in said second organic solvent is in the range of from 3 to 5 weight-%; whereby the concentration of poly(lactic- co-glycolic acid) in said second organic solvent is in the range of from 8 to 12 weight-%, and whereby the concentration of the second antibacterial drug in said second organic solvent is in the range of from 2 to 4 mg / ml, all amounts based on the total weight of the second solution; vii) immersing the surgical suture or mesh endoprosthesis comprising polypropylene with the adhesive layer comprising poly-s- caprolactone obtained in step iii) and the intermediate layer of microcontainers comprising poly-s-caprolactone, whereby the microcontainers are loaded with the first antibacterial drug, obtained in step v) into the second solution obtained in step vi), removing and drying it to obtain the surgical suture or the mesh endoprosthesis according to the present invention.

[0046] The single steps i) to vii) are now described in more detail.

[0047] The single steps i) to vii) are preferably performed under sterile conditions. An inert atmosphere is, however, not required.

[0048] In a preferred embodiment of the process of the present invention the first organic solvent used in step ii) is a linear Ci-4 alkanol or a branched C3-6 alkanol or any mixture thereof, preferably the first organic solvent used in step ii) is isopropanol, methanol or ethanol or any mixture thereof, more preferably the first organic solvent used in step ii) is ethanol or isopropanol, most preferably the first organic solvent used in step ii) is ethanol.

[0049] In a further preferred embodiment of the process of the present invention the second organic solvent used in step vi) is a linear C1-4 alkanol or a branched C3-6 alkanol or an ester of a C1-4 alkanoic acid with a linear C1-4 alkanol or a C3-6 ketone or an halogenated C1-2 hydrocarbon and any mixture thereof, preferably the second organic solvent used in step vi) is methanol, ethyl acetate, acetone or chloroform or any mixture thereof, more preferably the second organic solvent used in step vi) is a mixture of methanol and ethyl acetate, most preferably the second organic solvent used in step vi) is a mixture of methanol and ethyl acetate with a volume ratio of 2 : 3.

[0050] The adhesive layer comprising poly-s-caprolactone produced in step iii) has preferably a thickness of in the range of from 0.7 to 1 .7 pm, more preferably a thickness in the range of from 0.9 to 1 .5 pm, more preferably in the range of from 1 .0 to 1 .4 pm.

[0051] The concentration of the microcontainers comprising poly-s- caprolactone in the aqueous solution (step iv) is preferably in the range of from 10- 106 / ml to 30- 106 / ml, more preferably in the range of from 15- 106 / ml to 25 ■ 106 / ml, most preferably 20 ■ 106 / ml.

[0052] The intermediate layer of microcontainers comprising poly-s- caprolactone and the first anti-bacterial drug produced in step v) has preferably a thickness of < 10 pm.

[0053] The thickness of layers is determined by scanning electron microscopy by comparing the thickness of the uncoated thread to the thickness of the coated thread.

[0054] Preferred embodiments of the invention

[0055] The combination of any of the preferences given above with any other or more preferences given above is also encompassed within the scope of the present invention even if not explicitly mentioned.

[0056] Especially preferred embodiments of the antibacterial coating according to the present invention are listed below.

[0057] A first preferred embodiment of the present invention is directed to an antibacterial coating for surgical sutures and mesh endoprostheses comprising polypropylene, whereby the antibacterial coating comprises a) an adhesive layer comprising poly-s-caprolactone in an amount of at least 99 weight-%, based on the total weight of the adhesive layer, whereby the poly-s-caprolactone has a mass average molar mass in the range of from 75 to 85 kDa; b) an intermediate layer comprising poly-s-ca prolactone in an amount of at least 99 weight-%, based on the total weight of the intermediate layer, and microcontainers of poly-s-caprolactone, whereby these microcontainers are loaded with gentamicin sulfate and / or any other pharmaceutically acceptable salt of gentamicin, whereby the poly-s-caprolactone has a mass average molar mass in the range of from 75 to 85 kDa; c) an outer layer comprising poly(L-lactic acid) and poly(lactic-co- glycolic acid) and minocycline hydrochloride and / or any other pharmaceutically acceptable salt of minocycline, whereby the total amount of poly(L-lactic acid) and poly(lactic-co-glycolic acid) in the outer layer is at least 99 weight-%, based on the total weight of the outer layer, whereby the weight ratio of the poly(L-lactic acid) to the poly(lactic-co-glycolic acid) in the outer layer is in a range of from 2.5 : 10 to 3.5 : 10, whereby the poly(L-lactic acid) has a mass average molar mass in the range of from 65 to 75 kDa, whereby the poly(lactic-co-glycolic acid) has a mass average molar mass in the range of from 25 to 65 kDa, and whereby the molar ratio of lactic acid, preferably of L-lactic acid, to glycolic acid in poly(lactic-co-glycolic acid) is in the range of from 1 : 2 to 2 : 1 .

[0058] The amount of gentamicin sulfate and / or any other pharmaceutically acceptable salt of gentamicin packaged in the microcontainers in the inner layer is hereby preferably in the range of from 0.24 mg / cm2to 0.27 mg / cm2and / or the amount of the minocycline hydrochloride and / or any other pharmaceutically acceptable salt of minocycline in the outer layer is preferably in the range of from 2.6 mg / cm2to 3.0 mg / cm2.

[0059] A second preferred embodiment of the present invention is directed to an antibacterial coating for surgical sutures and mesh endoprostheses comprising polypropylene, whereby the antibacterial coating comprises a) an adhesive layer comprising poly-s-caprolactone in an amount of at least 99.9 weight-%, based on the total weight of the adhesive layer, whereby the poly-s-caprolactone has a mass average molar mass of 80 kDa; b) an intermediate layer comprising poly-s-ca prolactone in an amount of at least 99.9 weight-%, based on the total weight of the intermediate layer, and microcontainers of poly-s-caprolactone, whereby these microcontainers are loaded with gentamicin sulfate, whereby the poly-s-caprolactone has a mass average molar mass of 80 kDa; c) an outer layer comprising poly(L-lactic acid) and poly(lactic-co- glycolic acid) and minocycline hydrochloride, whereby the total amount of poly(L-lactic acid) and poly(lactic-co-glycolic acid) in the outer layer is at least 99.9 weight-%, based on the total weight of the outer layer, whereby the weight ratio of the poly(L-lactic acid) to the poly(lactic-co-glycolic acid) in the outer layer is 3 : 10, whereby the poly(L-lactic acid) has a mass average molar mass of 70 kDa, whereby the poly(lactic-co-glycolic acid) has a mass average molar mass in the range of from 30 to 60 kDa, and whereby the molar ratio of lactic acid, preferably of L-lactic acid, to glycolic acid in poly(lactic-co-glycolic acid) is 1 : 1. The amount of gentamicin sulfate packaged in the microcontainers in the inner layer is hereby preferably in the range of from 0.24 mg / cm2to 0.27 mg / cm2and / or the amount of the minocycline hydrochloride in the outer layer is preferably in the range of from 2.6 mg / cm2to 3.0 mg / cm2.

[0060] Surgical sutures or mesh endoprostheses comprising polypropylene, whereby the surgical sutures or mesh endoprostheses comprises an antibacterial coating according to any of the preferred embodiments given above are further objects of the present invention. Surgical sutures or mesh endoprostheses up to a length of 50 cm may be coated with the antibacterial coating of the present invention.

[0061] The invention is now further illustrated by the following non-limiting examples.

[0062] Examples

[0063] Polypropylene threads as e.g. commercially available from

[0064] Surgipro CP-41 1 suture material, Covidien AG (France) are used in the following example.

[0065] All steps in which the temperature is not explicitly specified are carried out at room temperature.

[0066] Example 1 : Process for the manufacture of polypropylene threads with an antibacterial coatina accordina to the present invention

[0067] A) Manufacture of an adhesive layer on polypropylene threads

[0068] Polypropylene (PP) monofilament threads with a diameter of 0,2 mm and a length of 0,5 m are pre-heated at a temperature of 70°C for 30 min and at sterile condition. The heated PP threads are then immersed in 50 ml of a 3 weight-% solution of poly-e-ca prolactone (PCL, Mw ~ 80 kDa, Sigma Aldrich, USA) in ethanol for 10 min at a temperature of 40 °C and at sterile conditions. The thus immersed polypropylene thread are then removed from the solution and dried at a temperature of 65 °C and at sterile conditions for 5 min, whereby polypropylene thread with an adhesive layer of poly-e-caprolactone are obtained with a thickness of 1 ,2 ± 0,5 m.

[0069] B) Manufacture of microcontainers comprising the antibacterial drug The microcontainers are prepared according to the process disclosed by V. Kudryavtseva et al. in ACS Appl Mater Interfaces, 2021 , 13, 2371 -2381 , doi: 10.1021 / acsami.0c21607 (“Biodegradable Defined Shaped Printed Polymer Microcapsules for Drug Delivery”).

[0070] Two polydimethylsiloxane (PDMS) master stamps, each with a microchamber size of 0.73 x 1 .08 pm and 50 x 106chambers, are uniformly filled each with 5 ml of a 2 weight-% solution of poly-e-caprolactone (PCL) in ethanol at room temperature and sterile conditions. The solvent is then evaporated at room temperature. Hereby two films of microcontainers are formed. The one film of microcontainers is not treated further, the other film of microcontainers is loaded with an antibacterial drug. The loading is carried out as follows: A powder of the antibacterial drug gentamicin sulfate (Sigma Aldrich, Germany) with a particle size < 1 pm is loaded into the microcontainers of the preformed PCL microcontainer film and evenly distributed at room temperature and at sterile conditions by pouring a layer of said drug powder with a thickness of approximately 1 mm onto the PCL microcontainer film and afterwards gently shaken the film in a horizontal position. Residues of drug particles not loaded into the microcontainers are then carefully removed by repeatedly shaken the stamp at an angle < 45°. On this film of microcontainers filled with the antibacterial drug gentamicin sulfate is then put the other film of microcontainers filled with PCL only. The two films are then moulded together under pressure, and then mechanically separated from the mould to form separate microcontainers which are detached from the films. The detached microcontainers are washed three times with 150 ml of deionised water at room temperature and sterile conditions. The thus obtained microcontainers containing the antibacterial drug gentamicin sulfate had a pyramidal shape and an average linear size of 1.1 ± 0.12 m; the average antibiotic content per microcontainer was 2.87x10~9mg.

[0071] Process B) can of course also be performed with another pharmaceutically acceptable salt of gentamicin, as well as with another antibacterial drug. If the same concentration of the drug in the microcontainers has to be achieved the water-solubility of the drug has to be taken into account since it affects the kinetics of the drug release and the anti-bacterial effect of the coating.

[0072] C) Manufacture of an intermediate layer on the adhesive layer of the polypropylene threads

[0073] 400- 106of the drug-loaded microcontainers obtained according to process B) disclosed above are dispersed in 20 ml of deionised water to obtain an aqueous suspension with a concentration of microcontainers of 20- 106per ml. Then, the PP threads coated with PCL according to process A) as disclosed above are immersed into the suspension of the drug- loaded microcontainers, while constantly stirring. Due to the chemical affinity of the polymer materials, the microcontainers are absorbed onto the surface of the PCL-coated PP threads. To ensure a firm attachment of the microcontainers to the PP threads, the PP threads with the absorbed microcontainers are subjected to convection drying at a temperature of 65°C for 10 minutes. This results in an intermediate layer of the encapsulated antibiotic drug, such as e.g. gentamicin sulfate used here, for a slow release.

[0074] D) Manufacture of an outer layer on the intermediate layer of the polypropylene threads

[0075] During this step, an outer layer of a polymer matrix containing a non-en- capsulated antibacterial drug, such as e.g. minocycline hydrochloride, is formed on the PP threads pre-coated with the drug-loaded microcontainers.

[0076] In 50 ml of a solution of methanol and ethyl acetate with a volume ratio of 2:3 150 mg of minocycline hydrochloride (Sigma Aldrich, USA), 2,3 g of poly(L-lactic acid) (PLA, Mw ~ 60 kDa, Sigma Aldrich, USA) and 7,7 g of poly(lactic-co-glycolic acid) (PLGA, 50:50, Mw ~ 30-60 kDa, Sigma Aldrich, USA) are dissolved by stirring at 45°C. The thus obtained homogeneous solution contains minocycline hydrochloride in a mass concentration of 3 mg / ml, PLA in a polymer mass content of 4 weight-%, and PLGA in a polymer mass content of 10 weight-%, all amounts based on the total weight of the solution.

[0077] The PP threads coated with the drug-loaded microcontainers obtained according to process C) as disclosed above are immersed for 10 seconds in said polymers / antibiotic solution, then pulled out and subjected to coaxial convection drying at a temperature of 65°C for 10 minutes to remove organic solvents and to enable the uniform crystallisation of the coating polymers.

[0078] E) Characteristics of the PP threads threads coated with the three layers: adhesive layer, intermediate layer and outer layer A high-performance liquid chromatography (HPLC) method using a UV- VIS detector was used to quantify the antibiotics in the coating. Different sections of the obtained threads (5 cm each) are separately placed in tubes with 3 ml of chloroform to dissolve the polymers in the coating (PCL, PLGA, PLA) and release the drugs (minocycline hydrochloride and gentamicin sulfate). The threads are incubated in chloroform for 1 hour.

[0079] Next, 5 ml of water is added to the samples, followed by shaking on an orbital shaker (Ditabis MO 10, Germany) for 1 h to transfer the antibiotics to the aqueous phase. Also, additionally the solutions are subjected to ultrasonic treatment (GRANBO GB0101 , China) to separate the organic and aqueous phases. 0,5 ml of the aqueous phase is collected from each sample for further quantitative antibiotic analysis.

[0080] The analysis is performed on a Shimadzu LC-6a high-performance liquid chromatograph (Shimadzu Corporation, Japan). A Zorbax Rx-C-18 column (2,1 x 150 mm, 5 m) (Agilent, Germany) is used for the separation. The column temperature is 30°C, the injection volume is 15 pl, and the flow rate is 0,7 ml / min.

[0081] A mixture of methanol, water and acetate buffer (0,025 M, pH = 9) in a volume ratio of 35:60:5 is used as the mobile phase, respectively.

[0082] Minocycline hydrochloride and gentamicin sulfate are recorded using a UV-VIS detector at wavelengths of 273 and 286 nm respectively, with retention times of 2,8±0,l min and 6,6±0,l min, respectively.

[0083] The calculation of the drug quantities is performed using pre-built calibration curves. The concentration range of the calibration curve for minocycline hydrochloride and gentamicin sulfate is 1 - 100 pg / ml with correlation coefficients of 0,998 and 0,995, respectively. The antibiotic content of the thread coating is 2,80 ± 0,43 mg / cm2of minocycline hydrochloride and 0,256 ± 0,093 mg / cm2of gentamicin sulfate.

[0084] Kinetic of the drug release

[0085] The kinetics of antibiotic release from the coating of PP threads are studied as follows: 5 cm of the obtained threads are placed in 50 mL of a phos- phate-buffered saline buffer solution (PBS, pH 7.4, SPL Lifesciences, South Korea) and incubated at temperature of 37°C and at sterile conditions with constant stirring at 1 10 rpm (DLAB, ms7-h550-pro, China). The experiment is performed in parallel on 5 pieces of threads of 5 cm2each.

[0086] Every 24 hours during the 40 days of the experiment, 0.5 ml of incubation solution is taken for quantitative analysis of the drugs by HPLC using UV-VIS detector, which is described in detail above. After the final time point (after 40 days), the threads coating is dissolved in chloroform for quantification of unreleased drugs. me point is expressed as, tibiotic released into the solution at the time point t, and mQ(g) and mQ(g) are the initial amounts of the antibiotic contained in the threads coating.

[0087] The kinetics of the antibiotics release from the coating of the threads are shown in Figure 1 , whereby the experimental data for minocycline hydrochloride are indicated by squares (left curve) and the experimental data for gentamicin sulfate are indicated by triangles (righ curve) . The x-axis represents hereby the time in days and the y-axis represents the cumulative drug release in %.

[0088] Thus, < 5% of each drug has not been released after 40 days.

Claims

Claims1 . An antibacterial coating for surgical sutures and mesh endoprostheses comprising polypropylene, whereby the antibacterial coating comprises: d) an adhesive layer comprising poly-s-ca prolactone; e) an intermediate layer comprising poly-s-ca prolactone and microcontainers of poly-s-caprolactone, whereby these microcontainers are loaded with a first antibacterial drug; and f) an outer layer comprising poly(L-lactic acid) and poly(lactic-co- glycolic acid) and a second antibacterial drug.

2. The antibacterial coating according to claim 1 , whereby the adhesive layer and / or the intermediate layer independently from each other comprise poly-e-caprolactone with a mass average molar mass in the range of from 15 to 145 kDa, preferably with a mass average molar mass in the range of from 60 to 100 kDa, more preferably with a mass average molar mass in the range of from 70 to 90 kDa, even more preferably with a mass average molar mass in the range of from 75 to 85 kDa, most preferably with a mass average molar mass of 80 kDa.

3. The antibacterial coating according to claim 1 and / or claim 2, whereby in the inner layer the amount of the first antibacterial drug packaged in the microcontainers of poly-s-caprolactone is in the range of from 0.02 to 0.45 mg / cm2, preferably it is in the range of from 0.09 to 0.41 mg / cm2, more preferably it is in the range of from 0.12 to 0.38 mg / cm2, even more preferably it is in the range of from 0.18 to 0.33 mg / cm2, most preferably it is in the range of from0.22 to 0.29 mg / cm2, oil amounts based on the surface of the inner layer in cm2.

4. The antibacterial coating according to any one or more of claims 1 to 3, whereby the amount of the poly-s-ca prolactone in the adhesive layer and / or the intermediate layer is at least 90 weight-%, preferably at least 92 weight-%, more preferably at least 95 weight- %, even more preferably at least 99 weight-%, most preferably at least 99.9 weight-%, based on the total weight of the adhesive layer and the intermediate layer, respectively.

5. The antibacterial coating according to any one or more of claims1 to 4, whereby the total amount of poly(L-lactic acid) and poly(lactic-co-glycolic acid) in the outer layer is at least 90 weight- %, preferably at least 92 weight-%, more preferably at least 95 weight-%, even more preferably at least 99 weight-%, most preferably at least 99.9 weight-%, based on the total weight of the outer layer.

6. The antibacterial coating according to any one or more of claims 1 to 5, whereby the weight ratio of the poly(L-lactic acid) to the poly(lactic-co-glycolic acid) in the outer layer is in a range of from 0.5 : 10 to 10 : 10, preferably it is in a range of from 1 : 10 to 5 : 10, more preferably it is in a range of from 2 : 10 to 4 : 10, even more preferably it is in a range of from 2.5 : 10 to 3.5 : 10, most preferably it is 3 : 10.

7. The antibacterial coating according to any one or more of claims 1 to 6, whereby the poly(L-lactic acid) used for the outer layer has a mass average molar mass in the range of from 35 to 105 kDa, preferably a mass average molar mass in the range of from 45 to 95 kDa, more preferably a mass average molar mass in the rangeof from 55 fo 85 kDo, even more preferably a mass average molar mass in the range of from 65 to 75 kDa, most preferably a mass average molar mass of 70 kDa.

8. The antibacterial coating according to any one or more of claims1 to 7, whereby the poly(lactic-co-glycolic acid) used for the outer layer has a mass average molar mass in the range of from 5 to 90 kDa, preferably a mass average molar mass in the range of from 10 to 80 kDa, more preferably a mass average molar mass in the range of from 20 to 70 kDa, even more preferably a mass average molar mass in the range of from 25 to 65 kDa, most preferably a mass average molar mass in the range of from 30 to 60 kDa.

9. The antibacterial coating according to any one or more of claims1 to 8, whereby the molar ratio of lactic acid, preferably of L-lactic acid, to glycolic acid in poly(lactic-co-glycolic acid) is in the range of from 1 : 5 to 5 : 1 , more preferably in the range of from 1 : 3 to 3 : 1 , even more preferably in the range of from 1 : 2 to 2 : 1 , most preferably it is 1 : 1 .

10. The antibacterial coating according to any one or more of claims 1 to 9, whereby the amount of the second antibacterial drug in the outer layer is in the range of from 1 to 5 mg / cm2, preferably it is in the range of from 1 .5 to 4 mg / cm2, more preferably it is in the range of from 2.1 to 3.5 mg / cm2, even more preferably it is in the range of from 2.3 to 3.3 mg / cm2, most preferably it is in the range of from 2.6 to 3 mg / cm2.1 1 . The antibacterial coating according to any one or more of claims1 to 10, whereby the first antibacterial drug and / or the second antibacterial drug are independently selected from each other from at least a drug being active against gram-negative bacteriaand / or gram-positive bacteria, preferably whereby the first antibacterial drug and / or the second antibacterial drug are independently selected from each other from a drug being active against at least one of the following bacteria: Pseudomonas, Proteus, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Serratia and Staphylococcus, more preferably whereby the first antibacterial drug and / or the second antibacterial drug are independently selected from each other from gentamicin, neomycin, streptomycin, ampicillin, chlorhexidine, rifampicin, vamcomy- cin, ofloxacin, tetracycline, ciproflaxin and minocycline as well as any of their pharmaceutically acceptable salts and any mixtures thereof, even more preferably whereby the first antibacterial drug and / or the second antibacterial drug are independently selected from each other from gentamicin, neomycin, streptomycin and minocycline as well as any of their pharmaceutically acceptable salts and any mixtures thereof, most preferably whereby the first antibacterial drug is gentamicin sulfate and / or any other pharmaceutically acceptable salt of gentamicin and the second antibacterial drug is minocycline hydrochloride and / or any other pharmaceutically acceptable salt of minocycline hydrochloride.

12. The antibacterial coating according to any one or more of claims1 to 1 1 , whereby the antibacterial coating comprises: a) an adhesive layer comprising poly-s-caprolactone in an amount of at least 99 weight-%, based on the total weight of the adhesive layer, whereby the poly-s-caprolactone has a mass average molar mass in the range of from 75 to 85 kDa; b) an intermediate layer comprising poly-s-ca prolactone in an amount of at least 99 weight-%, based on the total weight of theintermediate layer, and microcontainers of poly-s-caprolactone, whereby these microcontainers are loaded with gentamicin sulfate and / or any other pharmaceutically acceptable salt of gentamicin, whereby the poly-s-caprolactone has a mass average molar mass in the range of from 75 to 85 kDa; c) an outer layer comprising poly(L-lactic acid) and poly(lactic-co- glycolic acid) and minocycline hydrochloride and / or any other pharmaceutically acceptable salt of minocycline; whereby the total amount of poly(L-lactic acid) and poly(lactic-co-glycolic acid) in the outer layer is at least 99 weight-%, based on the total weight of the outer layer; whereby the weight ratio of the poly(L-lactic acid) to the poly(lactic-co-glycolic acid) in the outer layer is in a range of from 2.5 : 10 to 3.5 : 10; whereby the poly(L-lactic acid) has a mass average molar mass in the range of from 65 to 75 kDa; whereby the poly(lactic-co-glycolic acid) has a mass average molar mass in the range of from 25 to 65 kDa; and whereby the molar ratio of lactic acid, preferably of L-lactic acid, to glycolic acid in poly(lactic-co-glycolic acid) is in the range of from 1 : 2 to 2 : 1 .

13. A surgical suture or a mesh endoprosthesis comprising polypropylene, whereby the surgical suture or mesh endoprosthesis comprises an antibacterial coating according to any one or more of claims 1 to 12.

14. A process for the manufacture of a surgical suture or a mesh endoprosthesis according to claim 13, comprising the following steps: i) providing a surgical suture or mesh endoprosthesis comprising polypropylene; ii) providing a first solution comprising poly-s-caprolactone, especially with one or more of the preferences as given above in aconcentration in the range of from 1 to 4 weight-%, based on the total weight of the first solution, in a first organic solvent to obtain a first solution; iii) immersing the surgical suture or mesh endoprosthesis comprising polypropylene into the first solution provided in step ii), removing and drying it to obtain a surgical suture or mesh endoprosthesis comprising polypropylene with an adhesive layer comprising poly-s-ca prolactone; iv) providing an aqeuous solution comprising microcontainers comprising poly-s-ca prolactone, whereby the microcontainers are loaded with a first antibacterial drug; v) immersing the surgical suture or mesh endoprosthesis comprising polypropylene with the adhesive layer comprising poly-s- caprolactone obtained in step iii) into the aqueous solution of step iv), removing and drying it to obtain the surgical suture or mesh endoprosthesis further comprising an intermediate layer of microcontainers comprising poly-s-caprolactone, whereby the microcontainers are loaded with the first antibacterial drug; vi) providing a second solution comprising poly(L-lactic acid) and poly(lactic-co-glycolic acid) with one or more of their preferences as given above and a second antibacterial drug in a second organic solvent, whereby the concentration of poly(L- lactic acid) in said second organic solvent is in the range of from 3 to 5 weight-%; whereby the concentration of poly(lactic- co-glycolic acid) in said second organic solvent is in the range of from 8 to 12 weight-%, and whereby the concentration of the second antibacterial drug in said second organic solvent is inthe range of from 2 to 4 mg / ml, all amounts based on the total weight of the second solution; vii) immersing the surgical suture or mesh endoprosthesis comprising polypropylene with the adhesive layer comprising poly-s- caprolactone obtained in step iii) and the intermediate layer of microcontainers comprising poly-s-caprolactone, whereby the microcontainers are loaded with the first antibacterial drug, obtained in step v) into the second solution obtained in step vi), removing and drying it to obtain the surgical suture or the mesh endoprosthesis according to claim 13.

15. The process according to claim 14, whereby the first organic solvent used in step ii) is a linear Ci-4 alkanol or a branched C3-6 alkanol or any mixture thereof, preferably whereby the first organic solvent used in step ii) is isopropanol, methanol or ethanol or any mixture thereof, more preferably whereby the first organic solvent used in step ii) is ethanol or isopropanol, most preferably whereby the first organic solvent used in step ii) is ethanol; and / or whereby the second organic solvent used in step vi) is a linear C1-4 alkanol or a branched C3-6 alkanol or an ester of a C1-4 alkanoic acid with a linear C1-4 alkanol or a C3-6 ketone or an halogenated C1-2 hydrocarbon and any mixture thereof, preferably whereby the second organic solvent used in step vi) is methanol, ethyl acetate, acetone or chloroform or any mixture thereof, more preferably whereby the second organic solvent used in step vi) is a mixture of methanol and ethyl acetate, most preferably whereby the second organic solvent used in step vi) is a mixture of methanol and ethyl acetate with a volume ratio of 2 : 3.

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