The field of the invention

The present invention relates to antimicrobial biocompatible, absorbable-coated surgical sutures containing nanosilver particles and method for preparing the same. Surgical sutures containing nano silver particles of the present invention have inhibitory effect on a broad-spectrum of bacteria and fungi.

The nano silver particles present in the sutures are about 1-100 nm in diameter. The sutures of the present invention will prevent infections due to microbes on the wounds. The nanosilver containing sutures provide a variety of applications in health care and medicinal industry.

Background of the invention

The history of surgical sutures can be traced back to ancient Egypt. At the beginning of the 19th century metal threads were tested as suture material. After that the technique of closing wounds by means of needle and thread came to application. Metals including silver, copper, mercury, and zinc are known for anti-bacterial properties (Medical Biofilms: Detection, Prevention, and Control, John Wiley and Sons, P.291; 2003.) Silver and its compounds have been known since ancient times and have long been valued as a toxic metal on some bacteria, viruses, algae and fungi. Bacteria treated by these metals do not acquire resistance to the metals. Therefore, the bactericidal metals have advantages over the conventional antibiotics, which often cause the selection of antibiotic-resistant microorganism.

Among antimicrobial metals, silver is considered as a safe, broad-spectrum and effective antimicrobial agent. Publications have indicated that silver has natural bactericidal ability (. Journal of Biomedical Materials Research 52(4): 662-8y 2000), which can kill more than 650 types of microorganisms including bacteria and viruses. Silver ions adversely affects cellular metabolism to inhibit bacterial cell growth. When silver ions are absorbed into bacterial cells, silver ions suppress respiration, basal metabolism of the electron transfer system, and transport of substrate in the microbial cell membrane (O 2000 John Wiley & Sons, Inc. J Biomed Mater.Res, 52, 662-668, 2000). Silver ions also inhibit bacterial growth by producing active oxygen on the surface of silver powder and silver-plated articles.

Sutures are generally classified as absorbable and non-absorbable with each type being used for specific applications. A suture is made up of either natural (catgut, silk, linen, steel) or synthetic material (polyglycolic acid, polyglactin, polydioxone, polyglyconate, polyamide, polyester, poly propylene).

Self-dissolving sutures are usually coated with materials such as silicone, bee wax etc. to modify the handling and degrading rate of the suture. These often leave unwanted residues in the tissue after the suture itself is absorbed.

Prior art
In the US Patent No 6,979,491 B2 dated December 27, 2005, anti microbial yarn / fibers are used for making bandages, gauze, surgical clothes, antimicrobial clothes or clothing such as under wear, socks, shoe cushions, shoe linings, bed sheets, pillow shams, towels, woman hygienic products, lab coats, patient clothes etc. No disclosure is made in this patent in respect of nano silver coated suture,

In the Journal of Industrial Textiles, Vol. 35, No. 4, 323-335 (2006), apparels which are useful for hospital wards and operating theatres have been disclosed. These apparels are used to prevent spread of pathogens and MRSA (Methicillin-resistant Staphylococcus aureus, a bacterium responsible for difficult-to-treat infections in humans. It may also be referred to as multidrug- resistant) (i) in hospital and (ii) theatre gowns, dieatre linen, medical staff uniform, ward linen, bath towels, curtains , hand soap, surgical mask. Here again there is no reference to nano silver coated suture.

In US Patent Nb. 2005/ 0147657 Al- Silver containing natural and synthetic fibers are prepared and the fibers are used for making fabric/ wound dressing. No disclosure is made either for nano silver coated suture or the process for making such a suture in this patent.

US Patent No. 2005/0165372 and US Patent No. 2007/ 0213679 disclose an invention relating to sanitary articles containing nano silver used for absorbing body fluids. Here also no disclosure is made to nano silver coated sutures.

In US Patent No.2007/ 0207335 & US Patent No. 2006/ 0105010- disclosure is made on nano silver containing medical devices and implants useful as catheters, stents, abdominal plugs, feeding tube, wound dressings and urinary bladder. But there has been no disclosure on nano silver coated sutures.

In Japanese Patent No. 54-151669, Fibers which are specifically used for boots, shoes and pants have been disclosed but there is no mention of sutures or nano silver coated sutures.

In the European Polymer Journal 42 (2006) 2081-2087, Biodegradable poly (L-lactase) (PLA) ultrafine fibers containing nanosilver particles have been reported. These fibres are prepared by electro-spinning. Morphology of the Ag/PLA fibers and distribution of the silver nano particles have also been characterized. These fibers are only antimicrobial and are not biodegradable. The suggested applications of these fibers are for wound dressings and anti-adhesion membrane and not as sutures.

These fibers cannot be considered as sutures because sutures must be strong so that they do not break, non-toxic and hypoallergenic so as to avoid adverse reactions in the body, and flexible so that they can be tied and knotted easily. In addition, they must lack the so called "wick effect", which means that sutures must not allow fluids to penetrate the body through them from outside, which could easily cause infections.

Fibre is a class of material that are continuous filaments or are in discrete elongated pieces, similar to lengths of thread mainly used in the manufacturing of clothing.

Antimicrobial sutures are now available in the market based on US Patent No.3, 896,813. The antimicrobial activity of the suture is derived from the antibiotics present in the suture. One of the major drawbacks of the existing antibiotics is their highly specific nature with a particular antibiotic being targeted to inactivate or attack a particular bacterial component. In these types of sutures, many micro-organisms develop resistance to the antibiotics.

Nano silver fibres and yarns for maintaining hygiene and odour control have been disclosed and are used in Polartec gloves. It is incorporated into UK Army underwear and is used for EMC shielding, Military and Sportswear applications, anti-odour fabric.

Suture is a medical device that doctors and embalmers especially surgeons, use to hold skin, internal organs, blood vessels and all other tissues of the human body together, after they have been severed by injury, incision or surgery. Sutures are used to hold skin and other tissues of the body together. A cut can become infected, even when it is cleaned properly and stitched. Therefore whenever sutures are used, doctors prescribe antibiotics to prevent infection at the wounded site.

Replacing ordinary sutures by nano silver coated sutures can avoid the use of antibiotics. Moreover nano silver particles are resistant to most of the infectious microbes, which is not the case with antibiotics. It is to be noted that nano silver is more effective than a broad-spectrum antibiotic. It is therefore felt that if antimicrobial, biocompatible, absorbable coated surgical sutures containing nano silver particles are made available which are not only safe but also resistant to most of the infectious microbes they would very much help the medical profession

Objectives of the present invention

Therefore the main objective of the present invention is to provide novel antimicrobial, biocompatible, absorbable coated surgical sutures containing nano silver particles

Another objective of the present invention is to provide novel antimicrobial, biocompatible, absorbable coated surgical sutures containing nano silver particles having particle size in the range of 1-100 nanometers.

Another objective of the present invention is to provide a novel antimicrobial, biocompatible, absorbable coated surgical sutures containing nano silver particles which are evenly dispersed on the surface and pores of the coating materials used, which will be released to the contact object, thereby acting as fungicidal and bactericidal suture.

Yet another objective of the present invention is to provide a novel antimicrobial, biocompatible, absorbable coated surgical sutures containing nano silver particles which have no side effects arid does not invoke any allergic reaction in patients; hence safe to use for medical and healthcare purposes.

Yet another objective of the present invention is to provide a novel antimicrobial, biocompatible, absorbable coated surgical sutures containing nano silver particles which have longstanding inhibitory effect on broad spectrum of bacteria and fungi.

Still another objective of the present invention is to provide a novel antimicrobial, biocompatible, absorbable coated surgical sutures containing nano silver particles wherein the coating material used which is biodegradable selected from PGA (poly glycolic acid), PCL (polycaprolactone), PLA (polylactic acid), PVA (polyvinyl alcohol) and chitosan or their blends or their combinations which are also self-dissolving and hence do not leave any unwanted residue in the tissue after the suture itself is absorbed.

Still another feature is that the invention provides a method for making novel antimicrobial, biocompatible, absorbable coated surgical sutures containing nano silver particles Still another feature is that the invention provides a method for making novel antimicrobial, biocompatible, absorbable coated surgical sutures containing nano-silver particles which are suitable for large-scale industrial production.

The present invention has been developed taking advantage of the technological advances which have taken place in material sciences that has consequently created lots of advanced materials such as silver, copper etc in the nano meter regime. The nano regime imparts large number of applications due to the small size and increased surface activities. The present invention facilitates replacing ordinary sutures by nano silver coated sutures which has many benefits and advantages in achieving the bacterial inhibiting and eliminating ability of the suture for a prolonged period of time.

Summary of the present invention
Accordingly the present invention provides a novel antimicrobial, biocompatible, absorbable coated surgical sutures containing nano silver particles which inhibit growth of bacteria and fungi and prevent the infection due to microbes.

According to another embodiment of the present invention there is provided a novel antimicrobial, biocompatible, absorbable coated surgical sutures which inhibit growth of bacteria and fungi and prevent the infection due to microbes, .containing nano silver particles having particle size in the range of 1-100 nanometers.

According to another embodiment of the present invention there is provided antimicrobial, biocompatible, absorbable coated surgical sutures containing nanosilver particles which inhibit groSvth of bacteria and fungi and prevent the infection due to microbes wherein the nano silver particles have a diameter ranging between 1 nm and 300 nm; and which contain less than 1.0% by weight of silver.

According to another embodiment of the invention there is provided a process for the preparation of antimicrobial, biocompatible, absorbable coated surgical sutures containing nano silver particles which inhibits growth of bacteria and fungi and prevents the infection due to microbes which comprise:
(i) Preparing a solution of nano silver particles by dissolving a silver salt in a solvents.

(ii) Preparing a solution of biodegradable polymers, co-polymers, selected from PGA (poly glycolic acid), PCL (polycaprolactone), PLA (polylactic acid), PVA (polyvinyl alcohol) and chitosan or their blends or their combinations by dissolving in a solvent or by melt blending

(iii) Dispersing the solution of nano-silver particles obtained in step (i) in the solution or j melt obtained in step (ii) to obtain a uniform solution and .

(iv) Passing a suture through the solution obtained in step (iii) under vacuum to obtain the nano silver coated suture. The silver salt used in step (i) may be selected from silver nitrate, silver acetate, silver chloride, silver sulpha diazine and the like. The solution is made preferably using a suitable reducing agent and stabilizing agent. These agents may include sodium borohydride, starch, glucose, ethylene glycol, hydrazine, ascorbic acid, citric acid, trisodium citrate, sodium formaldehyde suphoxylate, sodium lauryl sulphate and the like.

The following two procedures may be adopted for the preparation of the silver nanoparticles.

Preparation of crystalline silver nano-powder
An aqueous solution of tri-sodium citrate was added to an aqueous solution of silver nitrate to maintain a ratio of at least 2:1. The drop-wise addition under continuous stirring at room temperature afforded a white precipitate. Alter the complete addition of tri-sodium citrate, stirring was continued for an additional 15 min. To this, drop-wise addition of aqueous sodium formaldehyde sulphoxylate afforded a dark gray precipitate, which was filtered off, washed with methanol and dried.

The dark gray powder obtained as described above that has a particle diameter of less than 50 nrn was suspended in water and was heated to a temperature between 50 and 100°C until a pale solution was formed. The pale solution was then centrifuged so that the bigger particles can be effectively separated. A clear yellow solution was then analyzed.

Synthesis of Ag nano particles (Sodium Dodecyl Sulphate & m-hydroxy benzaldehyde)
Silver nitrate solution was prepared by dissolving the required amount of AgN03 in (1:1) ammonia. Similarly, the m-hydroxy benzaldehyde solution and the surfactant solution having equal concentration to that of the silver nitrate solution were prepared in dehydrated ethanol and water, respectively. Then silver nitrate solution was taken in a well-cleaned dry beaker; Sodium dodecyl sulphate (SDS) solution was added to it and was mixed well for a few minutes (5 min for each set) by continuous stirring and the aldehyde solution was finally added to this mixture. A light yellow color appeared at room temperature

The solution was heated on a water-bath and the temperature was noted. When the temperature of the solution reached 80°C, the light yellow color of the solution started turning into deep yellow. Then the color gradually changed through yellowish brown to reddish brown and finally turned into brownish black
On further increasing the temperature of the solution, no perceptible change in color was observed.
The silver nanoparticles obtained by the above mentioned methods were characterized by UV- visible Spectrum and X-ray Diffractogram The obtained silver nanoparticles were characterized by UV-visible Spectrum and X-ray Diffractogram shown in Figures 1 , 2 and 3 of the drawing accompanying this specification It is observed that. the Nano silver solution gives an absorption peak at 473 nm. X-ray measurements gave the crystallite size of nano silver particles.

By changing the parameters employed in the processes described ab ove it is possible to prepare nano particles having particle size ranging from 10 nm to 100 nm.)

Preparation of Polycaprolnctone-Nanosilver composites
PCL—Nanosilver composites were prepared using the melt blending technique. In this method nano silver was added to the molten polycaprolactone. The composites were prepared in a microcompounder at a rotor speed of 60 rpm for 10 min at a temperature of 60°C. The virgin poly caprolactone has a melting point of 59°C. It has a tensile strength of 12.1 MPa, Young's modulus of 263 MPa and elongation at break of 348 %.

By employing similar methods other composites of PGA (poly glycolic acid), PCL (polycaprolactone), PLA (polylactic acid), PVA (polyvinyl alcohol) and chitosan or their blends or their combinations can also be made The suture of the present invention can be made by dipping a suture in the solution obtained as described above . The suture can be coated with the silver powder obtained as described above by laser coating or by sputtering under vacuum

The details of the invention are given in the Examples provided below which are given to illustrate the invention only and therefore should not be construed to limit the scope of the invention

EXAMPLE 1
A solution containing 30 g of polycaprolactone and 0.3 g of nanosilver of size 20 nm. was prepared by using the method described above To this solution a suture was dipped to obtain the suture coated with the solution . The mechanical properties of this suture : were tensile strength of 18.4 MPa, Elongation at break 479 % and Young's modulus of 348.2 MPa.

EXAMPLE 2
A Solution containing 30 g of polycaprolactone and 0.6 g of nanosilver of size 20 nm was prepared by the mnethod described above . To this solution a suture was dipped to obtain the suture coated with the solution . The mechanical properties of this suture were tensile strength of 19.8 MPa, Elongation at break 462 % and Young's modulus of 359.7 MPa.

EXAMPLE 3

A solution containing 30 g of polycaprolactone and 1.5 g of nanosilver of size 20 nm was prepared by the method described above . To this solution a suture was dipped to obtain the suture coated with the solution . The mechanical properties of this suture were : tensile strength of 21.4 MPa, Elongation at break 447 % and Young's modulus of 373.6 MPa.

EXAMPLE 4
A solution containing 30 g of polycaprolactone and 2.25 g of nanosilver of size 20 nm was prepared by the methoid described above . To this solution a suture was dipped to obtain the suture coated with the solution . The mechanical properties of this suture : were tensile strength of 20.2 MPa, Elongation at break 406 % and Young's modulus of 363.7 MPa.

EXAMPLE 5
A Solution containing 30 g of polycaprolactone and 3 g of nanosilver of size 20 nm. Was prepared by the method described above To this solution a suture was dipped to obtain the suture coated with the solution The mechanical properties of this suture were : tensile strength of 19.7 MPa, Elongation at break 393 % and Young's modulus of 354.6 MPa.

EXAMPLE 6
A bsolution containing 30 g of polycaprolactone and 4.5 g of nanosilver of size 20 nm was prepared by the method described above . To this solution a suture was dipped to obtain the suture coated with the solution . The mechanical properties of this suture were : tensile strength of 18.3 MPa, Elongation at break 386 % and Young's modulus of 301.5 MPa.

EXAMPLE 7
A solution containing 30 g of polycaprolactone and 6 g of nanosilver of size 20 nm was prepared by the method described above . To this solution a suture was dipped to obtain the suture coated with the solution . The mechanical properties of this suture were : tensile strength of 16.3 MPa, Elongation at break 359 % and Young's modulus of 292.1 MPa.

EXAMPLE 8

A solution containing 30 g of polycaprolactone and 3 g of nanosilver of size 10 nm. Was prepared by the method described above To this solution a suture was dipped to obtain the suture coated with the solution The mechanical properties of this suture were : tensile strength of 22.3 MPa, Elongation at break 465 % and Young's modulus of 363.2 MPa.

EXAMPLE 9
A solution containing 30 g of polycaprolactone and 3 g of nanosilver of size 50 nm. was prepared by the method described above To this solution a suture was dipped to obtain the suture coated with the solution The mechanical properties of this suture were : tensile strength of 16.1 MPa, Elongation at break 409 % and Young's modulus of 287.2 MPa.

EXAMPLE 10

Absolution containing 30 g of polycaprolactone and 3 g of nanosilver of size 100 nm. Was prepared by the method described above To this solution a suture was dipped to obtain the suture coated with the solution . The mechanical properties of this suture were : tensile strength of 14.4 MPa, Elongation at break 363 % and Young's modulus of 281.2 MPa.

Antimicrobial Study of the sutures prepared as described in the above described Examples

The antimicrobial study of the nanosilver incorporated sutures obtained by the processes described in the above described Examples were studied by disc diffusion method. The hot nutrient agar solution (20 mL) was poured into sterilized petridishes and allowed to attain room temperature, The seed layer medium was melted and cooled to about 450C with gentle shaking. The previously grown subculture was added to the seed layer medium' aseptically and mixed well. It was immediately lawned into the petridishes and allowed to attain room temperature. Then, wells were made (5 mm diameter) with a sterile cork borer. To these wells, 0.05 mL of the drug solution was added and the plates were allowed to cool for an hour to facilitate the diffusion. The plates were incubated at 37° C for 48 hours. At the end of inoculation period, the zones of inhibition around the wells were measured. A representative figure for the antimicrobial property of the suture of the present invention is given in figure 4. This test confirms that the sutures of the present invention possess antimicrobial activity against gram positive S. aureus ATCC 25923 and gram negative E.coli ATCC 25922 under the conditions of the test.

Advantages of the present invention

The nano silver coated suture is biocompatible without any side effects.

Nano silver incorporated lcoated suture is antibacterial, antifungal and antiviral.

Many bacteria develop resistance to the antibiotics, which became a serious problem. But nano silver coated suture of the present invention has no such effect

The nano silver coated suture can be employed for antimicrobial use, particularly due to its ability of not causing drug-resistance.

The suture can be used for effective control of wounds from infection. The suture can also be used for other applications such as tissue engineering, implantable biomedical devices, artificial organs and wound healing purposes. The suture prevents attachment of microbes to wounds, which open up the possibility of producing alternatives to the current commercial monofilament sutures.

We claim:

1. A novel antimicrobial, biocompatible, absorbable coated surgical sutures containing nano silver particles which inhibit growth of bacteria and fungi and prevent the infection due to microbes.

2. A novel antimicrobial, biocompatible, absorbable coated surgical sutures as claimed in claim 1 wherein the nano silver particles have a particle size in the range of 1-100 nanometers.

3. A novel antimicrobial, biocompatible, absorbable coated surgical sutures containing nanosilver particles as claimed in claims 1 & 2 wherein the nano silver particles have a diameter ranging between and 100 nm; and which contain less than 1.0% by weight of silver.

4. process for the preparation of antimicrobial, biocompatible, absorbable coated surgical surgical containing nano silver particles which inhibits growth of bacteria and fungi and prevents the infection due to microbes which comprises:

(i) Preparing a solution of nano silver particles by dissolving a silver salt in a solvents

(ii) Preparing a solution of biodegradable polymers, co-polymers, selected from PGA (poly glycolic acid), PCL (polycaprolactone), PLA (polylactic acid), PVA (polyvinyl alcohol) and chitosan or their blends or their combinations by dissolving in a solvent or by melt blending

(iii) Dispersing the solution of nano-silver particles obtained in step (i) in the solution or melt obtained in step ( ii) to obtain a uniform solution and .

(iv) Passing a suture through the solution obtained in step (iii) or under vacuum to obtain the nano silver coated suture.

5. A process as claimed in claim 4 wherein the silver salt used in step (i) is selected from silver nitrate, silver acetate, silver chloride, silver sulpha diazine and the like

6. A process as claimed in claims 4 & 5 wherein the solution in step ( i) is made using a e reducing agent and stabilizing agent, selected from sodium borohydride, starch, glucose, ethylene glycol, hydrazine, ascorbic acid, citric acid, trisodium citrate, sodium formaldehyde suphoxylate, sodium lauryl sulphate and the like.

7. A novel antimicrobial, biocompatible, absorbable coated surgical sutures containing nano silver particles which inhibit growth of bacteria and fungi and prevent the infection due to microbes substantially as herein described with reference to the Examples.

8. A process for the preparation of novel antimicrobial, biocompatible, absorbable coated surgical sutures containing nano silver particles which inhibit growth of bacteria and fungi and prevent the infection due to microbes substantially as herein described with reference to the Examples.