FIELD OF INVENTION:

This invention relates to Knot secure suture from polyethylene. Particularly, it relates to a suture made from linear low density polyethylene (LLDPE). More particularly, the invention relates to a suture with enhanced knot security in addition to having antimicrobial property. The invention also relates to a specific process for preparation of suture that imparts high knot security as well as antimicrobial property. The sutures provided by this invention exhibit good tensile strength, sharp decrease in stiffness or increase in compliance good preventive control on infection and improved knot security.

BACKGROUND OF TH INVENTION:

The suture is an important surgical filament having enormous potential in post-surgical applications. The following are some of the properties of sutures that play an important role for their selection keeping in view patients and surgeons compliance for safety and security purposes:
1. Knot security,
2. Handling ability,
3. Tensile strength,
4. Reaction with body tissue,
5. Tie down performance,
6. Infection control,
7. flexibility
The suture can be considered absorbable when they vanish after some time, generally within 60 days and not required to be removed from the sewn tissue. The sutures are made from cat gut collagenous material, LDPE, Polyglycolic Acid (PGA), Polypropylene, Polyester, Nylon etc.. Recently sutures made of synthetic polymers are preferred.
Commercially available sutures are generally coated with bioactive component such as triclosan. Alternatively, antimicrobial nature has been created in sutures by copolymerization of a monomer under radiation process so that the materials become bio-receptive. The immobilization of a drug such as tetracycline is carried out so that this can inhibit bacterial growth. However, in this process the grafting leads to significant loss in mechanical and knot strength and hence is not a viable solution. Also these sutures do not have required knot security and open up if the sufficient knot is not provided.

The prior art best known to the inventors include Patent No. 190584 (3032/DEL/98) for A method for preparation of an improved biocompatible nylon suture having anti-microbial property to Indian Institute of Technology, Delhi. The claimed process comprises: doping nylon chips with poly-N-vinyl-pyrrolidinone-iodine complex, drying the doped chips so obtained followed by melt-spinning and drawing filaments by known methods to get suture having anti-microbial property. As apparent, the crux of the invention resides in doping nylon chips with a specific component poly-N-vinyl-pyrrolidinone-iodine complex to have regulated release of the substance to combat post operational infection around sutures.

US Patent 4,557,264 relates to surgical sutures made from a blend of polypropylene and linear low density polyethylene. The patent discloses prior art using copolymers of propylene and ethylene or polypropylene and polyethylene, wherein polyethylene employed is a high density polyethylene. These sutures show improved elongations which are more than twice as high as polypropylene but this is undesirable as it impedes tie down properties. The invention teaches using mixtures of linear low density polyethylene (LLDPE) and high-molecular weight polypropylene wherein polyethylene is added in small amounts (0.1% to
25% by weight, preferably ranging from 1% to 16%) to make surgical sutures probably to regulate tensile strength. This is because the sutures made of polypropylene and polyethylene, exhibit significant loss in strength. So these materials have never become important commercially. The invention claims to have much lower Young’s Modulus as compared to the one either for pure polypropylene or mixtures of polypropylene with conventional polyethylene. According to the invention the sutures can be produced by extruding the polymer into filaments and subsequently orienting and annealing. It may be noted that the invention is silent with regard to improving knot security or any measures taken towards the same.

US Patent 4,983,180. The invention relates to braided multifilament surgical sutures coated to improve fiber lubricity and tie down performance. The synthetic polymers engaged are homopolymer and glycolidelactide copolymer. The coating composition is selected from the group consisting of sucrose fatty acid ester, beeswax, a mixture of stearic acid and copolymers of glycolide and lactide having a low degree of polymerization and paraffin wax. The patent further teaches that as expected, Tie-down performance of sutures is significantly improved when the sutures are coated with a lubricating material. However, as also shown from the data, knot security decreases when non-textured sutures are covered with such a lubricating material.
As apparent, the main intention is to impart improved lubricity in order to have better tie down performance. The invention does not teach or motivate the inventor on improved knot security.

US 7,029,490 is directed to a high strength abrasion resistant surgical suture material with improved tie down characteristics optionally with color coded for visualization and identification purposes. The sutures are formed of strands of ultra-high molecular weight long chain polyethylene braided with polyester, nylon or a bioabsorbable material. The present invention claims to advantageously provide a high strength surgical suture material with improved tie down characteristics. The polyester provides improved tie down properties. The invention does not mention about need to improving knot security let apart the mechanism to achieve the same.

As apparent from the available prior art, there is no indication about the knot security

The inventors have found out that when the LLDPE blended with silver ions are
given with plasma treatment enhances the surface roughness/friction which in turn enhances knot security in addition to improving binding of silver ion without deteriorating the tensile strength. As stated herein before, physical characteristics for considerations include handling ability, knot security. Unfortunately, these two requirements frequently do not coexist. Keeping this thing in mind the present invention is directed to a suitable material which holds both the properties with additional feature of antimicrobial nature.
Knot security of the suture is directly related to the strength of the raw material. In case of LLDPE suture, the tensile value comes out to be 220 MPa (~0.22 GPa) which is much higher than previously reported materials especially other polyolefines (PP). Even after blending with silver this value slightly changed. Tensile is used for the determination of knot strength of the LLDPE filament in terms of 190 MPa or 0.19 GPa. Further, plasma treatment of the LLDPE using different gases (O2 N2, NH3, steam and CO2) followed by surface etching introduce the roughness on the surface. Additionally it also helps in the increased binding of silver into the filament matrix.

OBJECTIVES OF THE INVENTION:

The main objective of the present invention is to provide a surgical suture with enhanced knot security and a process therefor avoiding/eliminating drawbacks associated with the existing prior art.

The other object is to provide a suture with enhanced knot security in addition to having antimicrobial property and sustainable release of silver from the filament.

Still other object of the present invention is to provide a surgical filament made from polyethylene, particularly, from linear low density polyethylene (LLDPE) blended with silver
The invention also relates to a specific process for preparation of suture including plasma treatment that imparts high knot security as well as antimicrobial property. The sutures provided by this invention exhibit good tensile strength, sharp decrease in stiffness or increase in compliance good preventive control on infection and improved knot security. The knot security of the sutures prepared by a specific process is 3 knots as comparison to existing suture have 5 or 6 knots, which is higher by 50% as compared to existing surgical suture.

DESCRIPTION OF THE FIGURES:

Figure 1. Schematic representation of the development of LLDPE-Ag monofilament
Figure 2. Tensile strength of LLDPE and LLDPE-Ag monofilament.
Figure 3. Schematic presentation of plasma exposure of the LLDPE-Ag monofilament.
Figure 4. 3D surface topography AFM images of (a) pure LLDPE filament and (b) plasma functionalized LLDPE-Ag sutures.
Figure 5. Phase contrast image of (a) pure LLDPE and (b) plasma functionalized LLDPE-Ag sutures.
Figure 6. SEM images of (a) and (b) LLDPE filament and (c) and (d) plasma functionalized LLDPE-Ag suture.
Figure 7. Silver ions release from LLDPE-Ag suture with varying release time in PBS at pH 7.4 and 37 °C. Total silver content in the sample is 1.23 ppm.
Figure 8. Exhibits Zone of inhibition of suture with varying concentration of silver against S. aureus
Figure 9. Colony formation analysis of pure LLDPE and LLDPE-Ag suture against E. coli (a) control (b) LLDPE-Ag and S. aureus (a) control (b) LLDPE-Ag.
Figure 10. Schematic representation of the alternate approach for the development of LLDPE-Ag monofilament
Figure 11. SEM-EDX images of the LLDPE-Ag suture (a) inner part (b) outer surface
Figure 12. Silver ions release from suture in PBS at pH 7.4 and 37 °C. Total silver content in the sample is 1.27 ppm.
Figure 13. Shows Colony formation study of suture against S. aureus (a) control (b) LLDPE-Ag and E. coli (c) control (d) LLDPE-Ag.

SUMMARY OF THE INVENTION:
Accordingly the present invention provides a knot secure suture from Linear Low Density Polyethylene (LLDPE) prepared by a process comprising steps:
(i) compounding LLDPE with silver nitrate to form a LLDPE-Ag blend;
(ii) extruding in to monofilament followed by;
(iii) subjecting the monofilament thus produced to plasma treatment to obtain a suture with improved knot security.

In one of the embodiments, the compounding may be effected in twin screw compounder wherein the concentration of silver varies from 0.5 to 2.0 wt. % of the total composition. The LLDPE used may be having melt flow index in the range of 0.5 to 10. The melt flow index 0.9 is preferable.

In other embodiment, the compounding may be effected by spraying silver nitrate in acetone/ water system on LLDPE chips to get LLDPE-Ag blend.

In another embodiment, the compounding may be effected at a temperature ranging from 200 to 2500C preferably at 2200C.

In yet other embodiment, the compounding may be effected under stirring at 125 to 170 rpm for a period of 2 to 10 minutes.

In yet another embodiment the monofilament may be extruded at a temperature ranging from 220 to 2800C preferably at 2400C by using single screw extruder after purging the system with nitrogen.

In still other embodiment, the monofilament may be subjected to plasma treatment using gases selected from O2, N2, CO2, NH3, steam.

In still another embodiment, the monofilament may be given plasma treatment for a period of 60 to 180 seconds.

The knot of the suture of the present invention may decrease from 6 to 2.

DETAILED DESCRIPTION OF THE INVENTION:

Polyethylene sutures are comparatively new products with enormous potential in postsurgical applications. The innovative aspect of the suture is that they exhibit high knot security along with antimicrobial nature when prepared in a particular manner. For the first time, a blending of silver and nanosilver with LLDPE and plasma treatment to create a frictional surface with antibacterial behavior has been suggested for surgical sutures. This friction leads to the better knot strength and better binding of silver both in the ionic as well as in the nano form.

LLDPE-Ag can be prepared by blending LLDPE with Silver nitrate. The blend further is drawn into monofilament and then subjected to plasma treatment to get the knot secure suture. Compounding of LLDPE was carried out with silver nitrate as shown schematically in Figure 1 with different composition in twin screw compounder at different conditions.
The LLDPE-Ag blend was chopped into chips with the help of cutter and use for further process. A single screw extruder was used for the spinning of LLDPE-Ag chips, the chopped chips were fed through the hoper of the extruder. The compounded material was extruded into monofilaments at varying conditions. The blend monofilaments were collected on a take-up winder and then collected on bobbins and stored at room temperature. LLDPE-Ag blend with varying amounts of AgNO3 were spun into monofilaments. Effect of draw ratio on developed LLDPE-Ag monofilament was also observed. When draw ratio increases the developed filament become thinner as comparison to undrawn monofilament.
The compounding is carried out at a temperature between 200 to 2500C for 2 to 10 minutes under stirring. The stirring may be effected at 125 to 170 rpm. The compounding may preferably carried out at 2200C at 150 rpm for 5 minutes.

Alternately, the silver nitrate in acetone/water system is sprayed on the PE chips to get LLDPE-Ag blend, followed by compounding and extrusion to monofilament suture with nanosilver formation which upon plasma treatment gives a surface with more friction and hence the knot security enhances. Different composition of silver nitrate was dissolved in water and acetone phase and sprayed on LLDPE granules and dried it at 80°C. The compounding of LLDPE-Ag composite was carried out in twin screw compounder. The LLDPE-Ag blend was chopped into chips with the help of cutter and use for further process. A single screw extruder was used for the spinning of LLDPE-Ag chips, the chopped chips were fed through the hoper of the extruder. Elemental analysis and quantification of silver in the LLDPE-Ag suture was carried out with SEM-EDX. The release profile of silver from suture was assessed in phosphate buffer at simulating physiological conditions. The antibacterial nature of the sutures was investigated against S. aureus and E. coli after being in contact with the suture for 24 h.

As shown in figure 2, the strength of filament did not decrease by compounding with Ag as comparison to pure LLDPE filament. Elongation of LLDPE-Ag sample are almost unchanged from that of the original filament The Young's modulus of LLDPE-Ag filament also stayed unchanged. Given that the use of sutures strongly depends on mechanical properties, their strength is the most frequently reported parameter. There should be a proper match between suture strength and tissue strength and for this reason the selection of proper suture depends also from the tissue involved. Furthermore, tensile properties of sutures are important when making a knot. If the material is too weak and the knotting force is stronger than tensile strength of suture material, suture can easily break while tightening the knot. In this regard, the developed monofilament was treated by (O2, N2, NH3, steam and CO2) plasma which enhances the surface roughness and knot security. A reference can be made to Figure 3. The surface morphology of the pure LLDPE and plasma functionalized LLDPE-Ag suture was investigated by AFM and SEM analysis (see figure 4). It is observed that the pure LLDPE filament shows the flat and smooth surface however, the plasma exposed surface shows hill-valley structure with significant non-homogeneity and rough surface. In conclusion, the generated surface roughness leading to higher surface friction and high knot security.

The release profile of silver from suture was assessed in phosphate buffer at simulating physiological conditions. In release plot, an initial burst of silver ions was observed and almost completely eluted its silver content in around 24 h. These data suggest that a fine tuning of release profiles can be accomplished playing important role in optimal amount of released silver ions may be selected according to the therapeutic needs. The antibacterial nature of suture was investigated by both qualitatively by zone of inhibition and quantitatively by a comparison of the number of viable against Gram positive bacteria (S. aureus) and Gram negative (E. coil).
The mechanism of bactericidal activity of silver ions as well as nanoparticles are generally believed that heavy metals react with proteins by combining the thiol (–SH) groups, which leads to the inactivation of the proteins. A clear zone of inhibition is formed around LLDPE-Ag filament with varying concentration of silver nitrate. It can be seen that as the silver concentration was increased, the zone of inhibition also increased. These results revealed that the antibacterial activity was due to the presence of silver ions in LLDPE-Ag filament. The interaction between LLDPE and silver will be polar interaction between each other and the release of silver may be observed due to the presence of radicals on the filament surface after plasma functionalization. These results are in agreement with the Ag-release experiments.
The invention is further illustrated with the following examples. However, they are given just to illustrate the working of the invention and should not construe the scope of the invention. Any modification, which is obvious to the persons working in this field, may fall within the scope of the present invention.
Example 1
Compounding of LLDPE
Two different grades of LLDPE (different melt flow index) were compounded with silver nitrate with different composition (0.5, 1 and 2%) in twin screw compounder. The compounding was carried out at a different conditions i.e. temperature of 200°C to 250°C at 125 to 170 rpm for 2 to 10 min in order to achieve suitable compositions and product for further procedure.
LLDPE with low melt flow index (0.9) was suitable for further use and from the above statement optimized conditions are temperature of 220°C at 150 rpm for 5 min. Silver nitrate composition was varied (0.5, 1 and 2%) in twin screw compounder. The LLDPE-Ag blends having different silver content were chopped into chips with the help of cutter and use for further process.
Spinning of LLDPE and LLDPE-Ag
A single screw extruder was used for the spinning of LLDPE and LLDPE-Ag chips, the chopped chips were fed through the hoper of the extruder and the system was purged with the nitrogen gas for 15 min. The compounded material was extruded into monofilaments at varying temperature of 220°C to 280°C. The blend monofilaments were collected on a take-up winder and then collected on bobbins and stored at room temperature. Pure LLDPE and LLDPE-Ag blend with varying amounts of AgNO3 (0.5, 1 and 2%) were spun into monofilaments. The schematic representation is shown in Figure 1. From above statement optimized spinning temperature is 240°C.
Drawing of LLDPE-Ag monofilament
Effect of draw ratio on developed LLDPE and LLDPE-Ag monofilament was also observed. Various draw ratios are considered for this study i.e. (1 to 5 draw ratio). When draw ratio increases the developed filament become thinner as comparison to undrawn monofilament. From above statement optimized draw ratio is 4.
Mechanical studies
The mechanical property of the monofilaments was observed by Instron under a load of 1 kg. Tensile properties of pure LLDPE and LLDPE-Ag filament are shown in Figure 2. As seen from the Fig. 2, the strength of filament was not decreased by compounding with Ag as comparison to pure filament. Elongation of LLDPE-Ag sample are almost unchanged from that of the original filament The Young's modulus of LLDPE-Ag filament is also not decreased as pure one. The LLDPE-Ag (1%) blend exhibited tensile strength of 0.22 GPa and modulus 1.10 GPa and optimized for further studies.
Example 2
Plasma Functionalization
Optimized LLDPE-Ag monofilament was plasma treated with different gases (O2 N2, NH3, steam and CO2) at varying plasma exposure time (60, 90, 120 and 180 s) in a RFGD (radio frequency glow discharge) low pressure plasma shown in Figure 3. The filament was loaded onto a template and placed in the plasma chamber. After the chamber was evacuated (high vacuum) different gases were purged into the chamber for 10 min. RF was switched on for a specified period during which the fabric is exposed to plasma. The filament was then dismounted from the template and kept sealed in a petri dish and stored at ambient conditions.
The optimized conditions after plasma functionalization was O2 plasma with 90 s exposure time is suitable for surface etching of LLDPE-Ag monofilaments. After plasma treatment, the surface roughness and knot security of the developed filament was increased.
Surface morphology studies
The surface morphology of the pure LLDPE and plasma functionalized LLDPE-Ag suture was investigated by AFM and SEM analysis. It is observed that in AFM studies the pure LLDPE filament shows the flat surface however, the plasma exposed surface shows hill-valley structure with significant non-homogeneity and rough surface (Figure 4 and 5). While in SEM image of both filaments sharp change in roughness was observed. In pure LLDPE filament, very smooth surface was observed while in plasma exposed sample of LLDPE-Ag surface roughness was clearly notice (Figure 6). In conclusion, the generated surface roughness leading to higher surface friction and high knot security.
Silver release studies
The release profile of silver from suture was assessed in phosphate buffer at pH 7.4 and 37°C, simulating physiological conditions. Initially the sample has 1.23 ppm of silver ions concentration in the filament. The total silver content was calculated by nitric acid digestion of the sample. In release plot (in Figure 7) an initial burst of silver ions was observed and almost completely eluted its silver content in around 24 h. These data suggest that a fine tuning of release profiles can be accomplished playing important role in optimal amount of released silver ions may be selected according to the therapeutic needs.
Example 4
Antimicrobial studies
The antibacterial nature of suture was investigated by both qualitatively by zone of inhibition and quantitatively by a comparison of the number of viable against Gram positive bacteria (S. aureus) and Gram negative (E. coil). A clear zone of inhibition is formed around LLDPE-Ag suture against S. aureus with varying concentration of silver nitrate (Figure 8). But in case of E. coli there is no formation of any zone due to the difference in cell wall structure. These results are in agreement with the Ag-release experiments.
It was also observed that LLDPE-Ag suture show the number of viable cells was decreased by 98% in both types of bacterial strains. The observed results were shown in Figure 9. These results enable to consider this filament for a clinical use on different implantation sites.
Example 5
Alternate approach for the development of LLDPE-Ag monofilaments
Alternately, the silver nitrate in acetone/water system is sprayed on the PE chips to get LLDPE-Ag blend, followed by compounding and extrusion to monofilament suture with nanosilver formation which upon plasma treatment gives a surface with more friction and hence the knot security enhances (Figure 10).
Silver nitrate (0.5, 1 and 2%) was dissolved in water and acetone phase and sprayed on LLDPE granules and dried it at 80°C. The compounding of LLDPE-Ag composite was carried out in twin screw compounder at a temperature of 220°C at 150 rpm for 5 min. The LLDPE-Ag blend was chopped into chips with the help of cutter and use for further process. A single screw extruder was used for the spinning of LLDPE-Ag chips, the chopped chips were fed through the hoper of the extruder and the system was purged with the blend for at least 30 min. The compounded material was extruded into monofilaments at temperature of 240°C.

Elemental analysis of silver in LLDPE-Ag monofilaments
Elemental analysis and homogeneous quantification of silver in the LLDPE-Ag suture was carried out with SEM-EDX. The EDX analysis of LLDPE-Ag samples shows 1.37% (wt) of silver present in the inner part of the filament while 1.22% (wt) is available on the outer part of the suture (in Figure 11). This result indicates the homogenous distribution of silver onto the filament.
Example 6
Silver release studies
The release study of silver ions from suture was assessed in PBS at pH 7.4 and 37°C by simulating physiological conditions. Initially the suture has 1.27 ppm of silver concentration. Low silver content leaches out form the suture even after 144 h of release (Figure 12). This release phenomenon indicates the slow release of the silver ions from the suture which makes them very good for long term use with good infection control.
Antimicrobial studies
The antibacterial nature of the sutures was investigated by quantitatively by a comparison of the number of viable against S. aureus and E. coli after being in contact with the suture for 24 h. It can be seen that suture shows the number of viable against S. aureus colony decrease by 100% while in case of E. coli decrease in viable count is only 93% may be because of different structure of cell wall of both bacteria (Figure 13).
Example 7
Knot secure studies
Knot secure property of the suture was observed by Instron under a load of 1 kg. Given that the use of sutures strongly depends on mechanical properties, their strength is the most frequently reported parameter. In this regard, the developed monofilament was treated by O2 plasma which enhances the surface roughness, knot strength as well knot security. The mechanical property of the LLDPE-Ag suture and after different plasma exposure time LLDPE-Ag suture was monitored by making knots. Initially with LLDPE-Ag suture the applied number of knots was 5 which are very equivalent to already reported sutures but after plasma functionalization the number of knots decreases up to 2 data presented in Table 1. When we increased the plasma time surface roughness increases which supports the decrease in the value of number of knots. But after 90 s not so much change was observed.
Table 1. Variation in number of Knots of LLDPE-Ag sutures with varying plasma time
S. no. Samples Plasma Time (s) Number of Knots
1. LLDPE-Ag 0 5
2. LLDPE-Ag 10 5
3. LLDPE-Ag 20 4
4. LLDPE-Ag 40 4
5. LLDPE-Ag 60 4
6. LLDPE-Ag 90 3
7. LLDPE-Ag 120 3

Accordingly, the scope of the present disclosure is by way of example rather than by way of limitation, and the subject disclosure does not preclude inclusion of such modifications, variations and/or additions to the present subject matter as would be readily apparent to one of ordinary skill in the art.
,CLAIMS:WE CLAIM:

1. A knot secure suture from Linear Low Density Polyethylene (LLDPE) prepared by a process comprising steps:
(i) compounding LLDPE with silver nitrate to form a LLDPE-Ag blend;
(ii) extruding in to monofilament followed by;
(iii) subjecting the monofilament thus produced to plasma treatment to obtain a suture with improved knot security.

2. The process as claimed in claim 1, wherein the LLDPE used may be having melt flow index in the range of 0.5 to 10 preferably 0.9 is preferable

3. The process as claimed in claim 1, wherein the compounding is effected in twin screw compounder wherein the concentration of silver varies from 0.5 to 2.0 wt. % of the total composition.

4. The method as claimed in claim 1 wherein the compounding is effected by spraying silver nitrate in acetone/water system on LLDPE chips to get LLDPE-Ag blend.

5. The process as claimed in claim 1, wherein the compounding is effected at a temperature ranging from 200 to 2500C preferably at 2200C.

6. The process as claimed in claim 1, wherein the compounding is effected under mixing for a period of 2 to 10 minutes at 125 to 170 rpm.

7. The process as claimed in claim 1, wherein the monofilament is extruded at a temperature ranging from 220 to 2800C preferably at 2400C by using single screw extruder after purging the system with nitrogen.

8. The process as claimed in claim 1, wherein the monofilament is extruded at a draw ratios of 1 to 5 preferably 4.
9. The process as claimed in claim 1, wherein the monofilament was subjected to plasma treatment using gases selected from O2, N2, CO2, NH3, steam.

10. The process as claimed in claim 1, wherein the monofilament was given plasma treatment for a period of 60 to 180 seconds.

11. The process as claimed in claim 1, wherein the knot of the suture decreases from 6 to 2.