ELECTRO SPUN NANOFIBROUS WOUND DRESSING AND A METHOD OF SYNTHESIZING THE SAME

• US 20130150763A1
• Filed: 12/07/2011
• Published: 06/13/2013
• Est. Priority Date: 12/07/2011
• Status: Active Grant

• Current Assignee: Esmaeil Mirzaei, Reza Faridi Majidi, Saeed Sarkar, Seyed Mehdi Rezayat
• Original Assignee: Esmaeil Mirzaei, Reza Faridi Majidi, Saeed Sarkar, Seyed Mehdi Rezayat
• Inventors: Sarkar, Saeed, Mirzaei, Esmaeil, Majidi, Reza Faridi, Rezayat, Seyed Mehdi
• Granted Patent: US 9,101,508 B2
• Time in Patent Office: Days
• US Class Current: 602/43
• CPC Class Codes: A61F 13/00 Bandages or dressings radioactive dressings A61N5/1029; Absorbent pads
• CPC Class Codes: A61F 13/00063 comprising medicaments or additives, e.g. odor control, PH control, debriding, antimicrobic drug delivery dressings A61K9/70; chemical aspect of the additives A61L15/00
• CPC Class Codes: A61F 13/01029 made of multiple layers
• CPC Class Codes: A61F 13/02 Adhesive bandages or dressings
• CPC Class Codes: A61F 13/0203 with fluid retention members
• CPC Class Codes: A61F 13/0206 with absorbent fibrous layers, e.g. woven or non-woven absorbent pads or island dressings
• CPC Class Codes: A61F 13/0213 the fluid retention member being a layer of hydrocolloid, gel forming material
• CPC Class Codes: A61K 9/00 Medicinal preparations characterised by special physical form nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61L 15/225 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 2300/30 Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: D04H 1/728 by electro-spinning electro-spinning methods and apparatus D01D5/0007

Abstract

The various embodiments herein provide an electro spun wound dressing comprising three nano fibrous layers and a method of synthesizing the same. The outer polymeric layer acts as a support layer for the other two layers and is hydrophilic in nature. The middle layer comprises a genipin cross linked reservoir layer loaded with a herbal extract of Melilotus officinalis and is hydrophobic or hydrophilic in nature. The second layer is cross-linked to control a release of the Melilotus officinalis extract in an aqueous environment. The third layer is a wound contacting inner layer comprising a non-cross-linked chitosan based nanofibrous layer that is hydrophilic in nature. Various additives are provided to enhance the mechanical or the chemical properties of the wound dressing and to control a release profile of the herbal extract.

Claims

1. An electro spun nanofibrous wound dressing comprises:

a first nanofibrous layer, and wherein the first nanofibrous layer is a polymeric layer, and wherein the first nanofibrous layer is an outer supporting layer, and wherein the first nanofibrous layer is hydrophobic in nature;

a second nanofibrous layer, and wherein the second nanofibrous layer is a polymeric layer, and wherein the second nanofibrous layer is a genipin cross linked middle reservoir layer loaded with a herbal extract, and wherein the second nanofibrous layer is hydrophobic or hydrophilic in nature, and wherein the herbal extract is a Melilotus officinalis extract and wherein the cross-linking of the second nanofibrous layer controls a release of the Melilotus officinalis extract in an aqueous environment;

a third nanofibrous layer, and wherein the third nanofibrous layer is a polymeric layer, and wherein the third nanofibrous layer is a wound contacting inner layer, and wherein the third nanofibrous layer is a non-cross-linked chitosan based nanofibrous layer, and wherein the third nanofibrous layer is hydrophilic in nature; and

additives, wherein the additives are selected from a group consisting of surfactants, block-co-polymers, salts and rubbers, and wherein the additives enhances a mechanical property and a chemical property of the wound dressing and wherein the additives controls a release profile of the herbal extract.

2. The wound dressing according to claim 1, wherein the first nanofibrous layer comprises a biocompatible polymers, and wherein the biocompatible polymers are a hydrophobic polymers, and wherein the hydrophobic polymers are selected from a group consisting of polyamides, polycaprolactone (PCL), poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and a combination thereof.

3. The wound dressing according to claim 1, wherein the first nanofibrous layer controls a vapour transmission rate and provides a moist environment on a surface of a wound to accelerate a wound healing process and wherein the first nanofibrous layer provides a barrier against a bacteria penetration thereby preventing the wound from an infection.

4. The wound dressing according to claim 1, wherein the second nanofibrous layer comprises a hydrophilic polymers or a hydrophobic polymers or a combination thereof and an extract of Melilotus officinalis, and wherein the hydrophobic polymers are selected from a group consisting of polyamides, polycaprolactone (PCL), poly (lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA), and a combination thereof, and wherein the hydrophilic polymers are selected from a group consisting of chitosan, gelatin, collagen, poly vinyl alcohol (PVA), polyethylene oxide (PEO), and a combination thereof, and wherein the hydrophilic polymer is chitosan.

5. The wound dressing according to claim 1, wherein the second nanofibrous layer comprises chitosan and poly ethylene oxide (PEO).

6. The wound dressing according to claim 1, wherein the extract of Melilotus officinalis is mixed to the second nanofibrous layer at a ratio of 50%, or 30% or 10% of a total weight of the second nanofibrous layer.

7. The wound dressing according to claim 4, wherein the chitosan is present in the second nanofibrous layer at a ratio up to 90 weight percent of second nanofibrous layer or less.

8. The wound dressing according to claim 1, wherein the genipin is present in the second nanofibrous layer at a ratio of 0.5-10% of chitosan by weight, and wherein a cross-linking of the chitosan based nanofibers with genipin decreases an initial burst release of a herbal extract and prolongs a release rate of the herbal extract.

9. The wound dressing according to claim 1, wherein the second nanofibrous layer has a high water absorption capability and wherein the second nanofibrous layer absorbs excess exudates coming out from a wound and wherein the second nanofibrous layer treats wounds with high exudates, and wherein the second nanofibrous layer is structurally stable in water.

10. The wound dressing according to claim 1, wherein the third nanofibrous layer comprises a biocompatible hydrophilic polymers and wherein the biocompatible hydrophilic polymers are selected from a group consisting of chitosan, collagen, gelatin, poly vinyl alcohol (PVA), polyethylene oxide (PEO) and a combination thereof.

11. The wound dressing according to claim 1, wherein the third nanofibrous layer comprises chitosan and poly ethylene oxide (PEO), and wherein chitosan is present in the third nanofibrous layer at a ratio of 90 weight percent of polymer or less.

12. The wound dressing according to claim 1, wherein the third nanofibrous layer forms a gel in presence of a water, and wherein a gel forming ability of the third nanofibrous layer helps the wound dressing to be removed from a wound easily in presence of a water, and wherein the third nanofibrous layer forms a barrier, and wherein the barrier controls a release of Melilotus officinalis extract from the second nanofibrous layer.

13. The wound dressing according to claim 1, wherein a release rate of the herbal extract depends on a type of polymer used, an amount of the herbal extract loaded, an extent of cross linking of the polymer and an addition of another polymer and additives.

14. A method of synthesizing an electro spun nanofibrous wound dressing comprises steps of:

forming a first nanofibrous layer, wherein the first nanofibrous layer is a polymeric layer, and wherein the first nanofibrous layer is in a form of a mat, and wherein the first nanofibrous layer acts as a support layer for a second nanofibrous layer and a third nanofibrous layer;

forming a second nanofibrous layer on the formed first nanofibrous layer, wherein the second nanofibrous layer is a polymeric layer, wherein the second nanofibrous layer is a chitosan polymer based nanofibrous layer loaded with Melilotus officinalis extract;

forming a third nanofibrous layer on the formed second nanofibrous layer, wherein the third nanofibrous layer is a polymeric layer, wherein the third nanofibrous layer is a chitosan polymer based layer without Melilotus officinalis extract; and

exposing the formed first nanofibrous layer, the second nanofibrous layer and the third nanofibrous layer to a water vapour at 30°

C. for 24 h.

15. The method according to claim 14, wherein an electro spun nanofibrous wound dressing is synthesized by an electro spinning process and wherein the electro spinning process is carried out using an electro spinning device, wherein the electro spinning device is operated in a voltage range of 1-35 kV and a syringe pump wherein the syringe pump is controlled to provide a flow rate within a range of 0.1-100 ml/h.

16. The method according to claim 15, wherein the electro spinning process is carried out at a temperature of 30°

C.

17. The method according to claim 15, wherein the electro spinning process is carried at a speed of 15 rpm.

18. The method according to claim 14, wherein the step of forming the first nanofibrous layer further comprises electro spinning a solution of polyamide 6,6, and wherein the solution of polyamide 6,6 is 20% (w/v) solution in a solvent, and wherein the solvent comprises a solution of formic acid and water in a ratio of 90/10 v/v, and wherein an electro spinning process is carried out at a voltage of 15 kV, and wherein a nozzle to a collector distance in an electro spinning device is kept at 10 cm and wherein an injection rate of the solution of polyamide 6,6 is fixed at 1 ml/h.

19. The method according to claim 14, wherein the step of forming the second nanofibrous layer further comprises:

preparing a chitosan solution in 80% (v/v) aqueous acetic acid solution, and wherein the chitosan solution is a 3% by weight solution;

preparing a poly ethylene oxide (PEO) solution in a 80% (v/v) aqueous acetic acid solution, and wherein the PEO solution is a 3% by weight solution;

mixing the prepared chitosan solution and the prepared poly ethylene oxide (PEO) solution to form a blend solution of Chitosan and PEO in different weight ratios, wherein the different weight ratios are within 90/10 to 50/50;

preparing a Melilotus officinalis extract solution in a 80% (v/v) aqueous acetic acid, and wherein the Melilotus officinalis extract solution has a concentration of 20% (w/w) concentration;

mixing the prepared Melilotus officinalis extract solution with the blend solution of Chitosan and PEO to obtain a polymeric extract solution with polymer to be extracted having a weight ratios of 100/0 to 50/50;

preparing a 10% genipin solution in ethanol;

adding the prepared genipin solution to the obtained polymeric extract solution, wherein the genipin is added at a ratio of 0.5 to 10 wt % of the chitosan in the polymeric extract solution;

electro spinning the polymeric extract solution including the genipin on the formed first nanofibrous layer, and wherein the electro spinning is done at a voltage of 20 kV, and wherein a distance between a nozzle to a collector of a electro spinning device is 12 cm and wherein an injection rate of the polymeric extract solution including the genipin is 1 ml/h.

20. The method according to claim 14, wherein the step of forming the third nanofibrous layer further comprises:

preparing a chitosan solution in 80% (v/v) aqueous acetic acid solution, and wherein the chitosan solution is a 3% by weight solution;

preparing a poly ethylene oxide (PEO) solution in a 80% (v/v) aqueous acetic acid solution, and wherein the PEO solution is a 3% by weight solution;

mixing the prepared chitosan solution and prepared poly ethylene oxide (PEO) solution to form a blend solution of Chitosan and PEO in different weight ratios, wherein the different weight ratios are within 90/10 to 50/50;

electro spinning the blend solution of Chitosan and PEO on the formed second nanofibrous layer, and wherein the electro spinning is done at a voltage of 20 kV, and wherein a distance between a nozzle to a collector of an electro spinning device is 12 cm and wherein an injection rate of the blend solution of Chitosan and PEO is 1 ml/h.