ANTIMICROBIAL WOUND CLOSURE MATERIALS, INCLUDING ANTIMICROBIAL SUTURES, AND METHOD FOR CLOSING A WOUND USING THE SAME
20200390931 ยท 2020-12-17
Inventors
- Robert DiLuccio (Viera, FL, US)
- Z. Paul Lorenc (Berkeley Heights, NJ, US)
- Randy Milby (Berkeley Heights, NJ, US)
Cpc classification
A61P17/02
HUMAN NECESSITIES
Y02A50/30
GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
A61L2300/404
HUMAN NECESSITIES
A61L31/16
HUMAN NECESSITIES
A61L17/005
HUMAN NECESSITIES
C08L27/18
CHEMISTRY; METALLURGY
A61L17/12
HUMAN NECESSITIES
International classification
A61L17/00
HUMAN NECESSITIES
A61B17/06
HUMAN NECESSITIES
A61L17/12
HUMAN NECESSITIES
Abstract
An antimicrobial suture comprising a filament and taurolidine.
Claims
1. An antimicrobial suture comprising at least one filament and taurolidine carried by said at least one filament.
2. An antimicrobial suture according to claim 1 wherein said at least one filament comprises a single filament.
3. An antimicrobial suture according to claim 1 wherein said at least one filament comprises a plurality of filaments.
4. An antimicrobial suture according to claim 3 wherein said plurality of filaments adhere to one another so as to constitute a singular structure.
5. An antimicrobial suture according to claim 4 wherein said plurality of filaments are co-extruded so as to form a composite structure.
6. An antimicrobial suture according to claim 4 wherein said plurality of filaments are braided together so as to constitute a singular structure.
7. An antimicrobial suture according to claim 1 wherein said at least one filament is resorbable.
8. An antimicrobial suture according to claim 1 wherein said at least one filament is non-resorbable.
9. An antimicrobial suture according to claim 1 wherein said at least one filament comprises a polymer.
10. An antimicrobial suture according to claim 9 wherein said at least one filament comprises a homopolymer.
11. An antimicrobial suture according to claim 1 wherein said at least one filament comprises a copolymer.
12. An antimicrobial suture according to claim 1 wherein said at least one filament comprises a material selected from the group consisting of polyglycolide (PGA), poly(glycolide-lactide) random copolymer (Vicryl), poly--dioxanone (PDS, PDSII), poly(glycolide-trimethylene carbonate block copolymer (Maxon), poly(glycolide-e-caprolactone)(Monocryl), glycolide-dioxanone-trimethylene carbonate triblock copolymer (Biosyn), polyethylene, polypropylene, poly(tetrafluroethylene)(Gore-Tex), stainless steel, polyesters, polyester-ethers, polyester-carbonates, polyamides, polyolephins, fluoropolymers, catgut, collagen, reconstituted collagen, cotton, linen and silk.
13. An antimicrobial suture according to claim 1 wherein said at least one filament comprises a matrix of material.
14. An antimicrobial suture according to claim 13 wherein said taurolidine is disposed within said matrix of material.
15. An antimicrobial suture according to claim 13 wherein said taurolidine is substantially evenly dispersed within said matrix of material.
16. An antimicrobial suture according to claim 13 wherein said taurolidine is restricted to one or more regions of said matrix of material.
17. An antimicrobial material according to claim 16 wherein said at least one filament is extruded, and further wherein said taurolidine is co-extruded with said at least one filament.
18. An antimicrobial suture according to claim 17 wherein said taurolidine comprises a taurolidine-containing matrix of material, and further wherein the material of said taurolidine-containing matrix of material is the same as the material of said matrix of material of said filament.
19. An antimicrobial suture according to claim 17 wherein said taurolidine comprises a taurolidine-containing matrix of material, and further wherein the material of said taurolidine-containing matrix of material is different than the material of said matrix of material of said filament.
20. An antimicrobial suture according to claim 13 wherein said taurolidine is disposed as a coating on said at least one filament.
21. An antimicrobial suture according to claim 20 wherein said coating is co-extruded with said at least one filament.
22. An antimicrobial suture according to claim 21 wherein said coating comprises a taurolidine-containing matrix of material, and further wherein the material of said taurolidine-containing matrix of material is the same as the material of said matrix of material of said filament.
23. An antimicrobial suture according to claim 21 wherein said coating comprises a taurolidine-containing matrix of material, and further wherein the material of said taurolidine-containing matrix of material is different than the material of said matrix of material of said filament.
24. An antimicrobial suture according to claim 20 further comprising an overcoating disposed on top of said coating of taurolidine.
25. An antimicrobial suture according to claim 1 wherein the antimicrobial suture comprises multiple filaments, and further wherein the taurolidine is positioned in the interstitial spaces between the filaments.
26. An antimicrobial suture according to claim 1 wherein said at least one filament is absorbent, and further wherein a taurolidine solution is introduced into said at least one filament.
27. An antimicrobial suture according to claim 1 wherein the proportion of taurolidine in the antimicrobial suture constitutes greater than about 1% by weight.
28. An antimicrobial suture according to claim 1 wherein the proportion of taurolidine in the antimicrobial suture constitutes greater than about 2% by weight.
29. An antimicrobial suture according to claim 1 wherein the proportion of taurolidine in the antimicrobial suture constitutes greater than about 6% by weight.
30. An antimicrobial suture according to claim 1 wherein the proportion of taurolidine in the antimicrobial suture constitutes greater than about 10% by weight.
31. An antimicrobial suture according to claim 1 further comprising barbs.
32. A method for treating a wound, the method comprising: providing an antimicrobial suture comprising at least one filament and taurolidine carried by said at least one filament; and treating the wound with the antimicrobial suture.
33. An antimicrobial surgical staple comprising: a surgical staple; and taurolidine carried by said surgical staple.
34. A method for treating a wound, the method comprising: providing an antimicrobial surgical staple, the antimicrobial surgical staple comprising a surgical staple, and taurolidine carried by the surgical staple; and treating the wound with the antimicrobial surgical staple.
Description
BRIEF DESCRIPTION OF DRAWINGS
[0077] These and other objects and features of the present invention will be more fully disclosed or rendered obvious by the following detailed description of the preferred embodiments of the invention, which is to be considered together with the accompanying drawings wherein like numbers refer to like parts and further wherein:
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DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0098] As noted above, prior art antimicrobial sutures are known in the art. It is beneficial to incorporate antimicrobial properties into sutures to combat the growth of microbes and germs, and to combat the creation and spread of infections by these microbes and germs. Such infections are complicating and deleterious events that often accompany wounds or surgical sites. By killing microbes and/or retarding the growth of microbes, one reduces the chance and/or severity of infection, thus helping to speed the healing process and increasing the success rates of procedures. Sutures are commonly used to close a wound or surgical site. Therefore, providing antimicrobial properties to sutures offers the opportunity to reduce infections associated with wounds or surgical sites.
[0099] In accordance with the present invention, taurolidine is incorporated in a suture so as to provide antimicrobial properties to the suture.
[0100] Taurolidine (bis(1,1-dioxoperhydro-1,2,4-thiadiazinyl-4)-methane) has antimicrobial and antilipopolysaccharide properties. It is derived from the amino acid taurine. The immunomodulatory action of taurolidine is reported to be mediated by priming and activation of macrophages and polymorphonuclear leukocytes.
[0101] Taurolidine has been used to treat patients with peritonitis and as an antiendoxic agent in patients with systemic inflammatory response syndrome. Taurolidine is a life-saving antimicrobial for severe abdominal sepsis and peritonitis. Taurolidine is active against a wide range of microorganisms that include gram positive bacteria, gram negative bacteria, fungi, mycobacteria and also bacteria that are resistant to various antibiotics such as MRSA, VISA, VRSA, ORSA, VRE, etc. Additionally, taurolidine demonstrates some anti-tumor properties, with positive results seen in early-stage clinical investigations using the drug to treat gastrointestinal malignancies and tumors of the central nervous system.
[0102] Taurolidine is also used as the active ingredient of anti-microbial catheter lock solutions for the prevention and treatment of catheter-related blood stream infections (CRBSIs) and is suitable for use in all catheter-based vascular access devices.
[0103] Bacterial resistance against taurolidine has not been observed in various studies to date.
[0104] Taurolidine acts by a non-selective chemical reaction. In aqueous solution, the parent molecule taurolidine forms equilibrium with taurultam and N-hydroxymethyl taurultam, with taurinamide being a downstream derivative.
[0105] The active agents of taurolidine are N-m derivatives of taurultam and taurinamide, which react with the bacterial cell wall, cell membrane, and proteins as well as with the primary amino groups of endo- and exotoxins. Microbes are killed and the resulting toxins are inactivated; the destruction time in vitro is 30 minutes.
[0106] Pro-inflammatory cytokines and enhanced TNF- levels are reduced when taurolidine is used as catheter lock solution.
[0107] Taurolidine decreases the adherence of bacteria and fungi to host cells by destroying the fimbriae and flagella and thus prevents the formation of biofilms.
[0108] A dose of 5 g of taurolidine over 2 hours, every 4 hours, for at least 48 hours, was given intravenously for the treatment of various sepsis condition and beneficial results were observed.
[0109] The present invention comprises the provision and use of a novel antimicrobial suture wherein the novel antimicrobial suture may comprise one or more filaments and taurolidine carried by the one or more filaments.
[0110] The one or more filaments may be in the form of a monofilament structure or a multifilament structure. Where the one or more filaments are in a multifilament structure, the one or more filaments may be joined together (e.g., by welding them together after extrusion or by braiding them together), or the one or more filaments may be co-extruded as a composite structure.
[0111] The taurolidine may be carried by the one or more filaments by substantially evenly dispersing the taurolidine within the matrix of a filament, or by positioning the taurolidine within one or more regions of the matrix of the filament (such as by co-extruding a matrix containing the taurolidine with the base matrix of the filament), or by positioning the taurolidine on the surface of the filament (e.g., by coating or co-extruding) or, in the case of a multifilament suture, by positioning the taurolidine within the interstitial spaces of the suture (i.e., the interstitial spaces between the filaments comprising the multifilament suture) or, where a filament is absorbent, by introducing a taurolidine solution into the filament.
[0112] In one preferred form of the invention, and looking now at
[0113] In one preferred form of the invention, and looking now at
[0114] In another preferred form of the invention, and looking now at
[0115] In one preferred form of the invention, the plurality of filaments 10 adhere to one another so as to constitute a singular structure.
[0116] In one preferred form of the invention, the plurality of filaments are co-extruded so as to form a composite structure.
[0117] In one preferred form of the invention, and looking now at
[0118] In one preferred form of the invention, the at least one filament is resorbable.
[0119] In one preferred form of the invention, the at least one filament is non-resorbable.
[0120] In one preferred form of the invention, the at least one filament comprises a polymer.
[0121] In one preferred form of the invention, the at least one filament comprises a homopolymer.
[0122] In one preferred form of the invention, the at least one filament comprises a copolymer.
[0123] In one preferred form of the invention, the at least one filament comprises a material selected from the group consisting of polyglycolide (PGA), poly(glycolide-lactide) random copolymer (Vicryl), poly-p-dioxanone (PDS, PDSII), poly(glycolide-trimethylene carbonate block copolymer (Maxon), poly(glycolide-e-caprolactone)(Monocryl), glycolide-dioxanone-trimethylene carbonate triblock copolymer (Biosyn), polyethylene, polypropylene, poly(tetrafluroethylene)(Gore-Tex), stainless steel, polyesters, polyester-ethers, polyester-carbonates, polyamides, polyolephins, fluoropolymers, catgut, collagen, reconstituted collagen, cotton, linen and silk.
[0124] In one preferred form of the invention, and looking now at
[0125] In one preferred form of the invention, and looking now at
[0126] In one preferred form of the invention, the at least one filament is extruded, and the taurolidine is co-extruded with the at least one filament.
[0127] In one preferred form of the invention, the taurolidine is co-extruded with the at least one filament, wherein the taurolidine is contained within a matrix which comprises matrix material plus taurolidine, and wherein the taurolidine-incorporating matrix material is the same matrix material as the remainder of the filament.
[0128] In one preferred form of the invention, the taurolidine is co-extruded with the at least one filament, wherein the taurolidine is contained within a matrix which comprises matrix material plus taurolidine, and wherein the taurolidine-incorporating matrix material is a different matrix material than the remainder of the filament.
[0129] In one preferred form of the invention, and looking now at
[0130] In one preferred form of the invention, the coating 30 is co-extruded with the at least one filament.
[0131] In one preferred form of the invention, the taurolidine-containing coating 30 is co-extruded with the at least one filament, wherein the taurolidine is contained within a matrix which comprises matrix material plus taurolidine, and wherein the taurolidine-incorporating matrix material is the same matrix material as the remainder of the filament.
[0132] In one preferred form of the invention, the taurolidine-containing coating 30 is co-extruded with the at least one filament, wherein the taurolidine is contained within a matrix which comprises matrix material plus taurolidine, and wherein the taurolidine-incorporating matrix material is a different matrix material than the remainder of the filament.
[0133] In one preferred form of the invention, and looking now at
[0134] In one preferred form of the invention, the antimicrobial suture comprises multiple filaments and the taurolidine is positioned in the interstitial spaces between the filaments.
[0135] In one preferred form of the invention, the antimicrobial suture comprises at least one filament and the at least one filament comprises a porous structure which has been exposed to taurolidine (e.g., dampened by, or immersed in, a solution containing taurolidine) such that taurolidine is present within the porous structure of the at least one filament.
[0136] In one preferred form of the invention, the antimicrobial suture comprises at least one filament which comprises a porous structure, and the antimicrobial suture is packaged immersed in, or dampened by, a solution comprising taurolidine (i.e., the antimicrobial suture is packaged wet).
[0137] In one preferred form of the invention, the antimicrobial suture comprises at least one filament which comprises a porous structure, and the antimicrobial suture has been exposed to a solution containing taurolidine and then desiccated before packaging (i.e., the antimicrobial suture is packaged dry).
[0138] In one preferred form of the invention, the proportion of taurolidine in the antimicrobial suture constitutes greater than about 1% by weight.
[0139] In one preferred form of the invention, the proportion of taurolidine in the antimicrobial suture constitutes greater than about 2% by weight.
[0140] In one preferred form of the invention, the proportion of taurolidine in the antimicrobial suture constitutes greater than about 6% by weight.
[0141] In one preferred form of the invention, the proportion of taurolidine in the antimicrobial suture constitutes greater than about 10% by weight.
[0142] In one preferred form of the invention, and looking now at
[0143] In another preferred form of the invention, there is provided a method for treating a wound, the method comprising:
[0144] providing an antimicrobial suture comprising at least one filament and taurolidine carried by the at least one filament; and
[0145] treating the wound with the antimicrobial suture.
[0146] In another preferred form of the invention, and looking now at
[0147] In another preferred form of the invention, there is provided a method for treating a wound, the method comprising:
[0148] providing an antimicrobial surgical staple, the antimicrobial surgical staple comprising a surgical staple, and taurolidine carried by the surgical staple; and
[0149] treating the wound with the antimicrobial surgical staple.
[0150] In accordance with the present invention, and by way of example but not limitation, a novel antimicrobial nylon suture may be provided, where the mono-filament type thread is similar to a plastic fishing line, except it is generally much thinner. The diameter of the nylon core of the suture is preferably about 2.5 decitex. Decitex is a measure of the thickness or diameter of a textile filament, and refers to the number of grams of weight of the yarn for each ten thousand meters of the yarn. As a more general proposition, the decitex number is a number used to define the size of the yarn, or the coarseness thereof, as generally a higher decitex number relates to a coarser yarn. To some extent, decitex also correlates to the strength of the yarn, as a higher decitex number tends to indicate a yarn that is stronger than one with a lower decitex number. In addition to its thickness, the strength of a particular yarn is also dependent upon the type of material used for the yarn. Nonetheless, for a particular type of yarn material, a higher decitex number will usually indicate a stronger yarn. Another analogous measurement parameter is the term denier. Denier is an American unit of measure and relates to the weight of nine thousand meters of a yarn.
[0151] Various exemplary configurations of a novel antimicrobial suture are shown in
[0152] When determining the ratio between the amount of antimicrobial and the nylon or the filament(s), it is generally desirable to strike a balance. If too little antimicrobial is used, it is likely that the antimicrobial properties of the product will be adversely affected. If, on the other hand, too much antimicrobial is used, it may affect the material properties of the suture and/or result in the cost of the antimicrobial suture being driven up unnecessarily.
[0153] It is also generally desirable to strike a balance in the manufacturing of the antimicrobial suture. By way of example but not limitation, it is important to strike a balance on the extrusion temperature of the polymer (in the case of an extruded polymer filament) and the antimicrobial so that degradation of the antimicrobial is avoided in the manufacturing process.
[0154] In one form of the present invention, once extruded, the antimicrobial suture material is sent in a long length roll to the suture manufacturer. The suture manufacturer cuts the roll of suture thread into segments of predetermined sizes to create suture segments of desired lengths. A needle is typically then added to the cut suture segments. Typically, the finished suture/needle assembly is packaged so that the sutured thread and needle are sealed in a sterile plastic pouch.
[0155] The suture so formed will have a look and feel that is generally identical to the antimicrobial sutures currently on the market, such as the Triclosan sutures sold by Johnson & Johnson's ETHICON division. The suture is strong and pliable.
[0156] The suture described above is generally well adapted for use as an external suture. However, modifications may be preferable for sutures that are to be used internally. For example, rather than using an antimicrobial only near the surface of the filment, it may be preferable to use a suture containing the antimicrobial within the core of the suture.
[0157] Additionally, it is anticipated that there will be wide variations in packaging. For example, some packaged sutures may have a suture length of only several centimeters. Other sutures may extend for up to 40 meters, e.g., for tasks that require one very long suture. Examples of various types, sizes and lengths of sutures can be found at a plurality of web sites, such as www.suturedirect.com.
EXAMPLES
[0158] By way of example, the following evaluations were done to assess the performance of Taurolidine-containing antimicrobial sutures. Zone of Inhibition studies on 3 representative microorganisms, as well as solution exposure of the antimicrobial filaments immersed in early phase concentrations of 3 test microorganisms, were conducted.
[0159] Filament Preparation.
[0160] Filaments were prepared using taurolidine and 2 test polymers to represent suture materials. The polymers were poly -caprolactone and -dioxanone. The tauroldine was extruded into the polymers by use of a Thermo Haake 16 mm Twin-Screw Extruder with a single hole die. The resulting structures were un-oriented filaments containing 2, 6 and 10% of taurolidine dispersed throughout the matrix of the filaments. Taurolidine was introduced as a powder while the polymers were provided as pellets. The filaments were then packaged prior to further evaluation.
[0161] Zone of Inhibition Evaluations.
[0162] Zone of Inhibition testing is a conventional method for estimating the inhibitory effects of antimicrobial substances against specific bacterial strains of interest. Zone of inhibition assays are useful for testing diffusible agents. As the agent diffuses away from the disk, the concentration decreases logarithmically. The sensitivity of the organism to the agent is judged by the appearance and size of a zone where no growth occurs, i.e., the Zone of Inhibition.
Example 1
Demonstration of Zone of Inhibition of Taurolidine Impregnated in Poly -Caprolactone and -Dioxanone
[0163] 400 l of early phase Pseudomonas aeruginosa (PAO1), the Staphylococcus epidermidis (S. epi 35984), and the multidrug resistant Staphylococcus aureus (MRSA) strain SA BAA-44) were plated separately into square plates. 200 l of each were introduced into 25 cm25 cm plates and 100 l were introduced into 15 cm15 cm plates. Four pieces of each filament were individually placed in the plates. The filaments tested were tauroldine loaded at 2, 6 and 10% dispersed in poly -caprolactone and 2, 6, and 10% dispersed in -dioxanone. After 24 hours of exposure the Zone of Inhibition surrounding each filament sample was measured in mm.
[0164] The results of the Zone of Inhibition studies are summarized in
[0165] Clearly the Zone of Inhibition increases with the increase in concentration of taurolidine in each of the filaments tested.
[0166] A graphic representation of the results is shown in the
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[0168] Solution Exposure of Filaments to Living Cultures.
[0169] Further tests were conducted to determine the effects of the solution exposure of taurolidine-containing filaments to living cultures.
Example 2
Demonstration of Bacteria Kills with Drug-Loaded Filaments Placed in Solutions with Living Microorganisms (Solution Exposure Experiments)
[0170] In this study, each of the filaments was placed in 12 well-bottom culture discs that had 1 ml Tryptic Soy Buffer containing 100 l of Early Phase Culture of each of the 3 bacteria: Pseudomonas aeruginosa (PAO1), Staphylococcus epidermidis (S. epi 35984), and Multidrug Resistant Staphylococcus aureus (MRSA) strain SA BAA-44) After 24 hours of exposure, the results shown in
[0171] More particularly,
[0172] PC1=2% taurolidine in -caprolactone
[0173] PC2=6% taurolidine in -caprolactone
[0174] PC3=10% taurolidine in -caprolactone
[0175] PVD=0% taurolidine in -dioxanone
[0176] PD1=2% taurolidine in -dioxanone
[0177] PD2=6% taurolidine in -dioxanone
[0178] PD3=10% taurolidine in -dioxanone
Total kills were observed for filaments that contained 6% or greater taurolidine in -caprolactone.
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[0180] SC1=2% taurolidine in -caprolactone
[0181] SC2=6% taurolidine in -caprolactone
[0182] SC3=10% taurolidine in -caprolactone
[0183] SVD=0% taurolidine in -dioxanone
[0184] SD1=2% taurolidine in -dioxanone
[0185] SD2=6% taurolidine in -dioxanone
[0186] SD3=10% taurolidine in -dioxanone
[0187] Total kills were observed for all the -caprolactone filaments that contained 2% or greater taurolidine and 6% or greater taurolidine in -dioxanone.
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[0189] EC1=2% taurolidine in -caprolactone
[0190] EC2=6% taurolidine in -caprolactone
[0191] EC3=10% taurolidine in -caprolactone
[0192] EVD=0% taurolidine in -dioxanone
[0193] ED1=2% taurolidine in -dioxanone
[0194] ED2=6% taurolidine in -dioxanone
[0195] ED3=10% taurolidine in -dioxanone
[0196] In
Additional Examples
[0197] It is possible to create a filament wherein the composition of the filament, and the quantity of taurolidine carried by that filament, varies. See, for example,
Modifications
[0198] It will be appreciated that still further embodiments of the present invention will be apparent to those skilled in the art in view of the present disclosure. It is to be understood that the present invention is by no means limited to the particular constructions herein disclosed and/or shown in the drawings, but also comprises any modifications or equivalents within the scope of the invention.