EP1778479A2 - Constructions microfibreuses hemostatiques - Google Patents

Constructions microfibreuses hemostatiques

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Publication number
EP1778479A2
EP1778479A2 EP05769365A EP05769365A EP1778479A2 EP 1778479 A2 EP1778479 A2 EP 1778479A2 EP 05769365 A EP05769365 A EP 05769365A EP 05769365 A EP05769365 A EP 05769365A EP 1778479 A2 EP1778479 A2 EP 1778479A2
Authority
EP
European Patent Office
Prior art keywords
hemostatic
compliant
elastomeric
set forth
absorbable
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP05769365A
Other languages
German (de)
English (en)
Inventor
Shalaby W. Shalaby
Scott M. Taylor
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Poly Med Inc
Original Assignee
Poly Med Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US11/175,636 external-priority patent/US7842749B2/en
Application filed by Poly Med Inc filed Critical Poly Med Inc
Publication of EP1778479A2 publication Critical patent/EP1778479A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L39/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Compositions of derivatives of such polymers
    • C08L39/04—Homopolymers or copolymers of monomers containing heterocyclic rings having nitrogen as ring member
    • C08L39/06—Homopolymers or copolymers of N-vinyl-pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0015—Electro-spinning characterised by the initial state of the material
    • D01D5/003—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
    • D01D5/0038—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion the fibre formed by solvent evaporation, i.e. dry electro-spinning
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
    • D01F8/04—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers
    • D01F8/10—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers with at least one other macromolecular compound obtained by reactions only involving carbon-to-carbon unsaturated bonds as constituent
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
    • D01F8/04—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers
    • D01F8/14—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers with at least one polyester as constituent
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
    • D01F8/04—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers
    • D01F8/16—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers with at least one other macromolecular compound obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds as constituent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/04—Materials for stopping bleeding
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L51/00—Compositions of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L67/00—Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Compositions of derivatives of such polymers

Definitions

  • fibrous constructs as in the cellulose-based cotton gauzes, can aid the process of hemostasis through interrupting the blood flow and subsequent coagulation.
  • Positively charged cellulosic fibers such as those based on chitosan, were later recognized as effective hemostatic constructs.
  • More recent understanding of the relevance of hemostasis to key biological events associated with wound healing, tissue ingrowth about prosthetic devices, and tissue engineering justified the need to explore means to modulating the hemostatic process to meet the specific requirements at different biological sites for optimum hemostasis and, hence, optimum functional performance at said sites.
  • this invention deals with mechanical, physicochemical, biochemical and pharmacological means to modulate the hemostatic process to meet the needs of specific individual biological events.
  • this invention relies on (1) electrostatic spinning technology to produce nanometer and micrometer diameter fibers with exceptionally high surface area for maximized effect on blood flow to initiate the clotting cascade through contact activation; (2) producing inherently compliant and elastic components of the fibrous construct through the use of segmented crystalline copolymers having triaxial or polyaxial chain configuration (i.e., three or many chain branches extending outward from a central atom); (3) controlling the composition of electrostatically spun fiber precursors to provide constructs with controlled solubility and biodegradability and hence, modulated short- and long-term retention of mass and biologically relevant properties; (4) controlling the surface charge of the electrostatically spun fibers to physicochemically modulate the hemostasis at will; and (5) incorporating i judiciously bioactive agents to prevent infection, pain, and/or promote desirable biological events.
  • Hemostasis is also compromised due to the presence of antiplatelet and anticoagulation agents, especially in patients undergoing cardiac or vascular surgery, as well as from changes associated with cardiopulmonary bypass.
  • topical hemostatic agents become useful adjuncts to the conventional methods of achieving hemostasis.
  • Table I A comprehensive list of currently available topical hemostatic agents, together with their key attributes, is presented in Table I.
  • Thrombin JMI Interacts with fibrinogen in the patient's Circulating fibrinogen and a means of blood to form a fibrin clot delivery (customarily used with Gelfoam sponges or powder) for use on active bleeding
  • Costasis also includes aprotinin (bovine-derived) -CoStasis/Dynastat requires patient's Dvnastat to prevent fibrinolysis.
  • CoStasis/ blood Dynastat include collagen, but not to be drawn and centrifiiged aprotinin -Can only apply to a dry, stationary tissue surface
  • Bioglue Glutaraldehyde and albumin cross- -Dry thoracic aortic tissue linked with proteins in tissue forming a -Tissue that can withstand exogenous strong adhesive cross-linking
  • hemostatic agent or material
  • any agent or material that is capable of arresting, stemming, or preventing bleeding by means other than inducing tissue growth alone.
  • something other than tissue growth is at least partially responsible for retarding or preventing bleeding.
  • the agent or material will be one that enhances blot clot formation. It will, of course, be appreciated that the agent or material may have the beneficial property of inducing tissue
  • CMC carboxymethylcellulose
  • cellulose calcium alginate, gelatin, or collagen, oxidized cellulose, such as TabotampTM
  • oxidized cellulose such as TabotampTM
  • Falling under the definition of "hemostatic agent” is the cellulose-based cotton gauze, the first and gold standard for all-time surgeons.
  • the early successful application of the cotton gauze as a hemostatic construct led several investigators to associate the fibrous structure of the gauze with the interruption of blood flow by initiating the clotting cascade through contact activation. This, in turn, provided the incentive to examine other fibrous constructs made primarily from natural materials, such as collagen, chitosan, and alginate, which led subsequently to the discovery of surface charge contribution to hemostasis.
  • EP Application No. 99933226.5 described a local absorbent hemostatic material coating the surface of fibers composed of material having biocompatibility and which can be degraded and absorbed in the living body, with extracted collagen.
  • the hemostatic material having biocompatibility and which can be degraded and absorbed in the living body was selected from the group consisting of polyglycolic acid, polylactic acid, copolymer of glycolic acid and lactic acid, polydioxanone, copolymer of glycolic acid and trimethylene carbonate, mixtures of polyglycolic acid and polylactic acid, and oxycellulose.
  • U.S. Patent No. 5,679,372 described an absorbable spun, cotton-like topical hemostat containing fibers entangled with each other and being made of atelcollagen obtained by
  • Each of the fibers has a diameter of 10 to 70 ⁇ M and a
  • the hemostat is swellable upon contact with blood. In use, the hemostat readily adapts to the shape of the hemorrhagic site, has an adhesiveness to a bleeding surface and provides an effective suppression of hemorrhage.
  • Growing interest in absorbable polymers in the form of scaffolds for tissue engineering has revived interest in electrospinning of synthetic polymers and, in particular, absorbable ones to produce nanofibers and microfibers with exceptionally high surface area. And a logical extension of this integrated know-how was the development of absorbable nanofibers and microfibers for use in hemostatic constructs. An outline of a generic electrospinning process and illustrations of key developments are summarized below.
  • Electrostatic spinning is the manufacturing technique most often associated with the production of polymeric nanofibers.
  • a polymer is dissolved in a solvent or melted and placed in a glass pipette tube, sealed at one end with a small opening in a necked down portion at the other end.
  • a high voltage potential up to 50 kv is then applied between the polymer solution and a collector near the open end of the pipette.
  • This process can produce nanofibers with diameters as low as 50 nanometers, although the collected web usually contains fibers with varying diameters from 30 nm to over one micron.
  • the production rate of this process is often measured in grams per hour per spin hole or nozzle, and the fiber strength (grams/denier) is thought to be very low, but is difficult to measure.
  • 6,689,166 also describes a tissue engineering device comprising a matrix of biocompatible non- woven nanofibrils comprising a non-degradable polymer selected from the group consisting of poly ethylenes and polyurethanes or a degradable polymer selected from the group consisting of poly(lactic acid-glycolic acid), and poly(lactic acid), poly(glycolic acid), poly (glaxanone), poly(orthoesters), poly(pyrolic acid), and poly(phosphazenes). It was further disclosed that the tissue engineering devices comprise absorbable organic polymers in the form of nanometer fibers that are produced by electrostatic spinning and an inorganic component made of calcium phosphate-based ceramic material.
  • biodegradable and/or bioabsorbable fibrous articles which are formed by electrospinning fibers of biodegradable and/or bioabsorbable fiberizable material, comprise a composite (or asymmetric composite) of different biodegradable and/or bioabsorbable fibers.
  • the biodegradable and/or bioabsorbable fibrous articles are formed by electrospinning fibers of biodegradable and/or bioabsorbable fiberizable material, in which the article contains a composite of different biodegradable and/or bioabsorbable fibers;
  • the biodegradable and/or bioabsorbable fiberizable material is a biodegradable and/or bioabsorbable polymer — the biodegradable and/or bioabsorbable polymer preferably contains a monomer selected from the group consisting of a glycolide, lactide, dioxanone, caprolactone, trimethylene carbonate, ethylene glycol, and lysine; and
  • fibrous articles formed by electrospinning different fibers of different materials in which the article contains a composite of different fibers containing fibers of at least one biodegradable material and fibers of at least one non-biodegradable material (preferably, the compositite of different fiber
  • Electrospinning is a useful process to produce polymeric fibers in the average
  • Fibers (1) possess a high aspect ratio that leads to a large specific surface; and (2) have been suggested to find applications ranging from optical and chemo sensor materials, nanocomposite materials, nanofibers with specific surface chemistry to tissue scaffolds, wound dressings, drug delivery systems, filtration, and protective clothing.
  • process parameters such as the applied electric field strength, flow rate, concentration, distance between the capillary and the target, have been explored in great detail for different polymer materials.
  • Most of the systems that have been investigated to date have utilized electrospinning from a single solution or melt.
  • the wettability of the electrospun mat can also be controlled by varying its porosity.
  • the porosity of the electrospun mat can be altered.
  • This study also described a new bicomponent electrospinning device and presented results of poly( vinyl chloride)/segmented polyurethane (PVC/Estane) and polyvinyl chloride)/poly(vinylidiene fluoride) ((PVC/PVDF) bicomponent fibers.
  • U.S. Application No. 10/267,823 described medical constructs made of microfibrous blends of absorbable and water-soluble polymers. And this application deals with a biodegradable, absorbent microfiber comprising a substantially homogeneous mixture of at least one hydrophilic polymer and at least one biodegradable polymer.
  • the absorbent fibers can be prepared by an electro hydrodynamic spinning of a substantially homogeneous polymer mixture and used as medical dressing for burns and wounds, cavity dressings, drug delivery patches, face masks, implants, drug carriers that comprise at least one microfiber electrospun from a polymer mixture.
  • the dressings can have variable water vapor penetration characteristics and variable biodegradation times.
  • Some embodiments of the invention provide dressings, implants, dermatological compatible compositions and drug carrier compositions which include totally biodegradable non-gel materials having water, blood, and other biological liquids absorption ability and possessing biological active properties like haemostatic and wound healing acceleration ability, which are irreversible, retain their contour and shape when wet, and do not exhibit any swelling. Additional embodiments provide totally biodegradable microfiber absorbents on the base of blends of synthetic biodegradable polyesters and poly(N-vinyl) lactams. These materials can be used in a variety of products such as cavity dressings, drug delivery patches, face masks, implants, drug carriers, wound and burn dressings with predicable biodegradation times and controlled
  • hemostasis and means to achieve it including the use of non- woven compositions made of nano/microfibers, it fails to describe novel means or compositions needed to modulate the hemostatic process at different biological sites with different requirements for optimum hemostasis that insures maximized functional performance. This provided the incentive to explore the subject of this invention.
  • this invention deals with (1) the technology of electrostatic spinning to produce nanometer and micrometer diameter fibers with exceptionally high surface area for maximized effect on blood flow to initiate the clotting cascade through contact activation; (2) produce inherently compliant and elastic components of the fibrous construct through the use of segmented crystalline copolymers having triaxial or polyaxial chain configuration (i.e., three or many chain branches extending outward from a central atom); (3) controlling the composition of electrostatically spun fiber precursors to provide constructs with controlled solubility and biodegradability and hence, modulated short- and long-term retention of mass and biologically relevant properties; (4) controlling the surface charge of the electrostatically spun fibers to physicochemically modulate the hemostasis at will; and (5) judicious incorporation of bioactive agents to prevent infection, pain, and/or promote desirable biological events.
  • This invention deals in general with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof.
  • Another general aspect of this invention deals with a hemostatic, compliant, elastomeric, fibrous construct comprising a non-woven material comprising fibers having a diameter in the range of from about 50 run to about 10 ⁇ m, the fibers having a core/sheath configuration and made from a synthetic absorbable/biodegradable polymer and at least one further polymer selected from a synthetic water-soluble polymer and another synthetic absorbable/biodegradable polymer.
  • a specific aspect of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution of at least one absorbable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, l,5-dioxepan-2-one, p-dioxanone, and a substituted or unsubstituted morpholine-2-5-dione.
  • Another specific aspect of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water- soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution comprising an absorbable/biodegradable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, 1,5- dioxepan-2-one, p-dioxanone, a substituted or unsubstituted morpholine-2-5-dione, and a synthetic, water-soluble polymer selected from the group represented by polyethylene oxide, polyethylene glycol, block copolymer of ethylene and propylene
  • Another specific aspect of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non- woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water- soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution comprising an absorbable/biodegradable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, I-lactide, glycolide, trimethylene carbonate, 1 ,5- dioxepan-2-one, p-dioxanone, a substituted or unsubstituted morpholine-2-5-dione, and a synthetic, water-soluble polymer selected from the group represented by polyethylene oxide, polyethylene glycol, block copolymer of
  • Another aspect of the invention pertains to hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non- woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution comprising an absorbable/biodegradable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, l,5-dioxepan-2-one, p-dioxanone, a substituted or unsubstituted morpholine-2-5-dione, and a synthetic, water-soluble polymer selected from the group represented by polyethylene oxide, polyethylene glycol, block copolymer of ethylene and prop
  • the present invention is directed to a hemostatic, compliant, elastomeric, fibrous construct as set forth in claim 3 wherein the water-soluble polymer is selected from the group consisting of polyethylene oxide, polyethylene glycol, and a block copolymer of ethylene and propylene glycols, and wherein the absorbable/biodegradable polymer further comprises pendant carboxyl groups ionically conjugated with a basic compound selected from the group consisting of lysine, arginine, a basic oligopeptide, antiseptic agents, anesthetic agents, analgesic agents, antimicrobial agents, anti-inflammatory agents, antiviral agents and growth promoters.
  • Another aspect of this invention deals with use of said fibrous construct, the subject of this invention as (1) a lint-free, absorbent surgical pad; (2) an adjuvant in surgical procedures selected from the group represented by vascular anastomosis with sutures or tissue adhesives, intestinal anastomosis with sutures, staples or tissue adhesives, vascular repair entailing synthetic vascular graft using sutures or tissue adhesives, and structural repair of a biological conduit entailing synthetic prosthesis using sutures, staples, or tissue adhesives; and (3) a pledget for repairing soft tissue as in liver, kidney, pancreas, and lung using sutures, clips, or tissue adhesives.
  • those constructs comprise a bioactive agent selected from the group represented by antimicrobials, antiseptics, anesthetics, analgesics, wound healing agents, anti-inflammatory compounds, antiviral agents and growth promoters.
  • a key aspect of the invention deals with a fibrous construct, subject of this invention, as a cover of a prosthetic device to aid/promote tissue ingrowth and mechanical stabilization of said prosthesis, wherein the prosthesis is selected from the group represented by endovascular grafts, perivascular wraps, vascular patches, endovascular stents, and similar stents for repairing biological conduits or restoring their function, endosteal implants, orthopedic implants, and implants for soft and hard tissue engineering. It is preferred that those constructs comprise a bioactive agent selected from the group represented by antimicrobials, antiseptics, anesthetics, analgesics, wound healing agents, anti-inflammatory compounds, antiviral agents and growth promoters.
  • Another key aspect of this invention pertains to a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein said construct comprises a bioactive agent selected from the group represented by antimicrobials, antiseptics, anesthetics, analgesics, wound healing, anti- inflammatory, growth promoters, and antiviral agents.
  • a specific aspect of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution comprising an absorbable/biodegradable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, 1 ,5-dioxepan-2-one, p-dioxanone, a substituted or unsubstituted morpholine-2-5-dione, and a synthetic, water-soluble polymer selected from the group represented by polyethylene oxide, polyethylene glycol, block copolymer of ethylene and
  • Another specific aspect of the invention pertains to a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water- soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution comprising an absorbable/biodegradable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, 1,5- dioxepan-2-one, p-dioxanone, a substituted or unsubstituted morpholine-2-5-dione, and a synthetic, water-soluble polymer selected from the group represented by polyethylene oxide, polyethylene glycol, block copolymer of ethylene and propy
  • An important aspect of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer fibers are produced by electrostatic spinning of a solution of at least one polymer that absorbs in less than 120 days and at least one additional polymer that absorbs after more than 120 days wherein each of these polymers is made from at lest one monomer selected for the group represented by ⁇ - caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, 1 ,5-dioxepan-2-one, p- dioxanone, and a substituted or unsubstituted morpholine-2-5-dione, and preferably at least one of the poly
  • a key segment of this invention pertains to a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non- woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution of at least one absorbable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, l,5-dioxepan-2-one, p-dioxanone, and a substituted or unsubstituted morpholine-2-5-dione, wherein such construct is part of the external wall of a vascular graft having a surface-activated, non-absorbable lumen compris
  • the surface activation is due to the presence of surface sulfonated fibers onto which is immobilized a hemocompatible molecule such as albumin. It is also preferred that those constructs comprise a bioactive agent selected from the group represented by antimicrobials, antiseptics, anesthetics, analgesics, wound healing agents, anti ⁇ inflammatory compounds, antiviral agents and growth promoters.
  • a bioactive agent selected from the group represented by antimicrobials, antiseptics, anesthetics, analgesics, wound healing agents, anti ⁇ inflammatory compounds, antiviral agents and growth promoters.
  • a clinically important aspect of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water- soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution of at least one absorbable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl- lactide, 1-lactide, glycolide, trimethylene carbonate, l,5-dioxepan-2-one, p-dioxanone, and a substituted or unsubstituted morpholine-2-5-dione, wherein such construct is a part of the internal surface of a partially absorbable woven or knitted mesh for repairing defective walls as in abdominal wall,
  • Another segment of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof and wherein such a construct is a part of a composite fabric comprising chitosan fibers or derivatives thereof.
  • hemostasis as (1) the stoppage of bleeding, and (2) the stoppage of the flow of blood in a vein or artery, as with a tourniquet.
  • the Webster's Medical Desk Dictionary (1986) defines hemostasis as (1) stoppage or sluggishness of blood flow, and (2) arrest of bleeding (as by a hemostatic agent).
  • this invention was intended to deal with (1) the technology of electrostatic spinning to produce nanometer and micrometer diameter fibers with exceptionally high surface area for maximized effect on blood flow and initiating the clotting cascade through contact activation; (2) production of at least one inherently compliant, elastic component of the fibrous construct through the use of segmented crystalline copolymers having triaxial or polyaxial chain configuration (i.e., three or many chain branches extending outward from a central atom); (3) control of the composition of electrostatically spun fiber precursors to provide constructs with controlled solubility and biodegradability and hence, modulated short- and long-term retention of mass and biologically relevant properties; (4) control of the surface charge of the electrostatically spun fibers to physicochemically modulate the hemostasis at will; and (5) judicious incorporation of bioactive agents to prevent infection, pain, and/or promote desirable biological events.
  • the present invention deals with a multicomponent and preferably bicomponent nano- or microfibrous construct produced by at least one absorbable, inherently compliant elastomeric polymer and second polymer that can be water-soluble or non-absorbable.
  • a multicomponent and preferably bicomponent nano- or microfibrous construct produced by at least one absorbable, inherently compliant elastomeric polymer and second polymer that can be water-soluble or non-absorbable.
  • electro-spinning solvent, and electrospinning conditions one can produce constructs that can be optimally suited for use at different biological sites to meet the specific requirements for optimum performance and/or restore the respective biological functions at said treated sites.
  • This invention also deals with the formation of bicomponent nanofiber/microfibers having a core/sheath structure, wherein the core and sheath are based primarily on two physicochemically different polymers.
  • the production of bicomponent nanof ⁇ bers/microfibers can be achieved through controlling (1) the polymer molecular weight; (2) the type of spinning solvent and hence, the solvent-polymer interaction; (3) concentration of the individual polymers; and (4) the electrospinning parameters.
  • at least one bioactive agent can be added to the spinning solution to meet the specific requirements at the treated biological site.
  • An illustrative example of the basic tenets of this invention is associated with the use of different agents at sites where hemostasis is paramount to wound healing. It is well recognized that the process of wound healing is one that is complex and can be compromised by a number of contributing factors. One such factor is infection of the wound.
  • Another illustrative example of the tenets of this invention is associated with the use of the hemostatic, compliant, elastomeric, multicomponent, fibrous construct as an absorbable wrap or a pledget to aid in completing a less invasive vascular anastomosis using sutures, staples, and/or tissue adhesives.
  • the absorbable fibrous construct, subject of this invention will function as a substrate for even distribution of the tissue adhesive about the anastomotic site and form a bridge between the suture and tissue adhesive leading to more mechanically secure anastomosis.
  • Another illustrative example of the tenets of this invention deals with the absorbable elastomeric, compliant, fibrous construct as a microporous template for effective application of tissue adhesive in repairing wounds or lacerations of exceptionally soft tissue as in the lung, liver, and pancreas.
  • a partially absorbable elastomeric, compliant, fibrous construct as a component of a vascular graft wherein the lumen of the graft is made of a non-absorbable woven or knitted yarn as for example, polypropylene, that is preferably treated to prevent hemostasis at the blood contacting surface while the outer wall of the graft is made primarily of an absorbable, compliant, elastomeric microfiber which can preferably contain a growth promoter to allow early and continued tissue ingrowth into the outer wall of the graft; this is to insure initial and long-term stability at the treated site.
  • This invention deals in general with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof.
  • Another general aspect of this invention deals with a hemostatic, compliant, elastomeric, fibrous construct comprising a non-woven material comprising fibers having a diameter in the range of from about 50 nm to about 10 ⁇ m, the fibers having a core/sheath configuration and made from a synthetic absorbable/biodegradable polymer and at least one further polymer selected from a synthetic water-soluble polymer and another synthetic absorbable/biodegradable polymer.
  • a specific aspect of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution of at least one absorbable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, l,5-dioxepan-2-one, p-dioxanone, and a substituted or unsubstituted morpholine-2-5-dione.
  • Another specific aspect of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non- woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water- soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution comprising an absorbable/biodegradable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, 1 ,5- dioxe ⁇ an-2-one, p-dioxanone, a substituted or unsubstituted morpholine-2-5-dione, and a synthetic, water-soluble polymer selected from the group represented by polyethylene oxide, polyethylene glycol, block copolymer of
  • the present invention is directed to a hemostatic, compliant, elastomeric, fibrous construct as set forth in claim 3 wherein the water-soluble polymer is selected from the group consisting of polyethylene oxide, polyethylene glycol, and a block copolymer of ethylene and propylene glycols, and wherein the absorbable/biodegradable polymer further comprises pendant carboxyl groups ionically conjugated with a basic compound selected from the group consisting of lysine, arginine, a basic oligopeptide, antiseptic agents, anesthetic agents, analgesic agents, antimicrobial agents, anti-inflammatory agents, antiviral agents and growth promoters.
  • a basic compound selected from the group consisting of lysine, arginine, a basic oligopeptide
  • antiseptic agents from the group consisting of lysine, arginine, a basic oligopeptide
  • anesthetic agents analgesic agents
  • antimicrobial agents anti-inflammatory agents
  • Another specific aspect of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water- soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter
  • fibers are produced by electrostatic spinning of a solution comprising an
  • absorbable/biodegradable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, 1,5- dioxepan-2-one, p-dioxanone, a substituted or unsubstituted morpholine ⁇ 2-5-dione, and a synthetic, water-soluble polymer selected from the group represented by polyethylene oxide, polyethylene glycol, block copolymer of ethylene and propylene glycol, polyhydroxyethyl methacrylate, poly-N-vinyl pyrrolidone and polyethylene glycol interlinked by an ester or urethane-containing interlink, and wherein the absorbable/ biodegradable and water-soluble constituents of the spinning solution result in bicomponent fibers having a core and sheath component derived primarily from the water-soluble and absorbable/biodegradable polymer, respectively.
  • Another aspect of the invention pertains to hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution comprising an absorbable/biodegradable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, l,5-dioxepan-2-one, p-dioxanone, a substituted or unsubstituted morpholine-2-5-dione, and a synthetic, water-soluble polymer selected from the group represented by polyethylene oxide, polyethylene glycol, block copolymer of ethylene and propy
  • Another aspect of this invention deals with use of said fibrous construct, the subject of this invention as (1) a lint-free, absorbent surgical pad; (2) an adjuvant in surgical procedures selected from the group represented by vascular anastomosis with sutures or tissue adhesives, intestinal anastomosis with sutures, staples or tissue adhesives, vascular repair entailing synthetic vascular graft using sutures or tissue adhesives, and structural repair of a biological conduit entailing synthetic prosthesis using sutures, staples, or tissue adhesives; and (3) a pledget for repairing soft tissue as in liver, kidney, pancreas, and lung using sutures, clips, or tissue adhesives.
  • those constructs comprise a bioactive agent selected from the group represented by antimicrobials, antiseptics, anesthetics, analgesics, wound healing agents, anti-inflammatory compounds, antiviral agents and growth promoters.
  • a key aspect of the invention deals with a fibrous construct, subject of this invention, as a cover of a prosthetic device to aid/promote tissue ingrowth and mechanical stabilization of said prosthesis, wherein the prosthesis is selected from the group represented by endovascular grafts, perivascular wraps, vascular patches, endovascular stents, and similar stents for repairing biological conduits or restoring their function, endosteal implants, orthopedic implants, and implants for soft and hard tissue engineering. It is preferred that those constructs comprise a bioactive agent selected from the group represented by antimicrobials, antiseptics, anesthetics, analgesics, wound healing agents, anti-inflammatory compounds, antiviral agents and growth promoters.
  • Another key aspect of this invention pertains to a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein said construct comprises a bioactive agent selected from the group represented by antimicrobials, antiseptics, anesthetics, analgesics, wound healing, anti ⁇ inflammatory, growth promoters, and antiviral agents.
  • a specific aspect of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution comprising an absorbable/biodegradable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, 1 ,5-dioxepan-2-one, p-dioxanone, a substituted or unsubstituted morpholine-2-5-dione, and a synthetic, water-soluble polymer selected from the group represented by polyethylene oxide, polyethylene glycol, block copolymer of ethylene and
  • Another specific aspect of the invention pertains to a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups
  • the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution comprising an absorbable/biodegradable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, 1,5- dioxepan-2-one, p-dioxanone, a substituted or unsubstituted morpholine-2-5-dione, and a synthetic, water-soluble polymer selected from the group represented by polyethylene oxide, polyethylene glycol, block copolymer of ethylene and propylene glycol, polyhydroxyethyl methacrylate, poly-N-vinyl pyrrolidone and polyethylene glycol interlinked by an ester or urethane-containing interlink, and preferably the water-soluble component is polyethylene glycol or block copolymer of ethylene and propylene glycol comprising a conjugate of carboxyl-bea
  • An important aspect of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer fibers are produced by electrostatic spinning of a solution of at least one polymer that absorbs in less than 120 days and at least one additional polymer that absorbs after more than 120 days wherein each of these polymers is made from at lest one monomer selected for the group represented by ⁇ - caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, l,5-dioxepan-2-one, p- dioxanone, and a substituted or unsubstituted morpholine-2-5-dione, and preferably at least
  • one of the polymers comprises a linear chain absorbable copolyester and an additional
  • a key segment of this invention pertains to a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution of at least one absorbable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl-lactide, 1-lactide, glycolide, trimethylene carbonate, l,5-dioxepan-2-one, p-dioxanone, and a substituted or unsubstituted morpholine-2-5-dione, wherein such construct is part of the external wall of a
  • the surface activation is due to the presence of surface sulfonated fibers onto which is immobilized a hemocompatible molecule such as albumin. It is also preferred that those constructs comprise a bioactive agent selected from the group represented by antimicrobials, antiseptics, anesthetics, analgesics, wound healing agents, anti-inflammatory compounds, antiviral agents and growth promoters.
  • a bioactive agent selected from the group represented by antimicrobials, antiseptics, anesthetics, analgesics, wound healing agents, anti-inflammatory compounds, antiviral agents and growth promoters.
  • a clinically important aspect of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non-woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water- soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof, wherein the nanometer and micrometer diameter fibers are produced by electrostatic spinning of a solution of at least one absorbable polymer made from at least one monomer selected from the group represented by ⁇ -caprolactone, dl- lactide, 1-lactide, glycolide, trimethylene carbonate, 1 ,5-dioxepan-2-one, p-dioxanone, and a substituted or unsubstituted morpholine-2-5-dione, wherein such construct is a part of the internal surface of a partially absorbable woven or knitted mesh for repairing defective walls as in abdominal wall,
  • Another segment of this invention deals with a hemostatic, compliant, elastomeric, multicomponent, fibrous construct comprising non- woven nanometer and micrometer diameter fibers made from at least one polymer selected from the groups represented by synthetic absorbable/biodegradable heterochain polymers, synthetic water-soluble heterochain polymers, synthetic water-soluble homochain polymers, and polysaccharides or derivatives thereof and wherein such a construct is a part of a composite fabric comprising chitosan fibers or derivatives thereof.
  • Example 1 Synthesis of a Caprolactone/Trimethylene Copolymer and Use as Triaxial Initiator for End-grafting /-Lactide/ ⁇ -Caprolactone to Produce Crystalline Segmented Triaxial Copolymer (PAX * )
  • the polymeric initiator was prepared by ring opening polymerization of ⁇ -caprolactone (0.25 mole) and
  • TMC stannous octanoate
  • triethanolamine as the initiator
  • the polymerization was achieved by heating at 180°C for 3 hours.
  • the resulting product was cooled below 150 0 C and then mixed under nitrogen atmosphere with /-lactide (0.45 mole) and ⁇ -caprolactone (0.05 mole).
  • the system was stirred while heating to 190-200°C to achieve a uniform melt.
  • the temperature was then lowered to 140 0 C and the reaction was continued without stirring for 24 hours.
  • the polymer was isolated, ground, dried, and heated under reduced pressure to remove unreacted monomer.
  • polymer(s) in one or more solvents e.g., chloroform, CHCb and/or dichloromethane DCM
  • solvents e.g., chloroform, CHCb and/or dichloromethane DCM
  • the resulting non-woven fabric is collected on a metallic cylinder (e.g., different diameter stainless steel cylinder) capable of controllable radial and axial motion.
  • the electrospun construct at a thickness of 0.1 to 2 mm, is collected for subsequent characterization for (1) bulk composition using NMR and IR; (2) surface composition using electron spectroscopy for chemical analysis (ESCA); (3) fiber diameter and fabric uniformity (SEM); (4) molecular weight (GPC, inherent viscosity); (5) thermal transitions associated with crystalline melting, glass transition melting, or heat of fusion; (6) burst testing/radial deformation (in-house modified cone penetration test); (7) tensile properties using a Universal MiniBionix tensile tester Model 858; (8) oxygen and water vapor permeation (standard ASTM protocol); (9) surface free energy (static and dynamic contact angle measurements); and (10) partial water solubility and associated change in morphology and mass (SEM and mass loss).
  • ESA electron spectroscopy for chemical analysis
  • SEM
  • Example 4 The PAX/PEO-100 was shown to comprise microfibers with a PEO-100-rich water soluble sheath. The preponderance of polyethylene oxide on the surface was verified by ESCA and fractional dissolution of the sheath in deionized water. The PAX/PEO-100 fabric was shown to be more hydrophilic and wettable as compared to the PAX control.
  • Example 8 Electrostatic Co-spinning of a Mixed Solution of PAX and Urethane-
  • Example 10 Electrostatic Co-Spinning of PAX and Polyvinylpyrrolidone (PVP) and Comparison with a PAX control
  • Example 11 Electrostatic Co-spinning of PAX with PVP/Iodine Complex and Comparison with a PAX Control
  • Example 12 Incorporation of Trichlosan Sodium in a PCL/PAX Microfabric
  • the PCL/PAX microfabric from Example 5 was treated with a 2% solution of trichlosan sodium in 2-propanol following a similar protocol to that disclosed in U.S. Patent No. 6,551,610.
  • the treated specimen was dried and shown to release about 7% of the incorporated drug in 3 days when incubated in deionized water at 37°C.
  • Example 13 Surface Activation and Testing of the Microfabric
  • Example 14 Evaluation of the Relative Hemostatic Properties of Nano-/Microfibrous Non- woven Fabric
  • a 20 x 20 x 0.2 mm fabric specimen was tested for its ability to arrest bleeding in a standard liver laceration and punctured vena cava of an anesthetized rabbit and/or rat model.
  • the hemostatic property was shown to substantially improve by increasing the composite fabric wettability, decrease in diameter of constituent fibers, and/or positive surface charge as compared with a PCL or PAX control. All examined specimens showed superior hemostatic properties as compared to commercial specimens of chitosan non-woven fabric, chitosan foam, and cotton gauze.

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Abstract

L'invention porte sur des constructions fibreuses élastomères formées de plusieurs composants, de nano/micro fibres non tissées possédant une configuration de noyau et de gaine essentiellement constituée d'un polymère absorbable et de préférence hydrosoluble. De préférence, les nano/micro fibres sont fabriquées par centrifugation électrostatique. Des agents bioactifs convenables peuvent être intégrés dans la construction en fonction de l'utilisation clinique des constructions.
EP05769365A 2004-07-16 2005-07-08 Constructions microfibreuses hemostatiques Withdrawn EP1778479A2 (fr)

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US11/175,636 US7842749B2 (en) 2004-08-02 2005-07-05 Tissue protecting spray-on copolymeric film composition
PCT/US2005/024144 WO2006019600A2 (fr) 2004-07-16 2005-07-08 Constructions microfibreuses hemostatiques

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US8758447B2 (en) 2009-06-30 2014-06-24 Ethicon, Inc. Device and method for repair of urological structures
US20100331963A1 (en) * 2009-06-30 2010-12-30 Jackie Donners Method of Making Suture-Less Hollow Scaffolds
EE05698B1 (et) 2010-12-29 2014-02-17 Tartu �likool Meetod hemostaatilise bioadhesiivse v?rgustiku saamiseks
CN107205955B (zh) 2014-09-29 2021-11-09 内布拉斯加大学董事会 纳米纤维结构及其合成方法和用途
US11471481B2 (en) * 2016-06-29 2022-10-18 Iview Therapeutics, Inc. Rapid-deposition thin-film forming compositions as effective wound care treatment
US11318224B2 (en) 2016-09-28 2022-05-03 Board Of Regents Of The University Of Nebraska Nanofiber structures and methods of use thereof
US11738116B2 (en) 2017-06-09 2023-08-29 Board Of Regents Of The University Of Nebraska Expanded nanofiber structures comprising electrospun nanofibers and a plurality of holes and methods of making and use thereof
WO2019060393A1 (fr) 2017-09-19 2019-03-28 Board Of Regents Of The University Of Nebraska Structures de nanofibres et procédés d'utilisation de celles-ci
WO2020159946A1 (fr) * 2019-01-28 2020-08-06 Board Of Regents Of The University Of Nebraska Pansements à base de nanofibres électrofilées et leurs procédés de fabrication et d'utilisation

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