EP2331743B1 - Fibres enrobées d'un peptide - Google Patents

Fibres enrobées d'un peptide Download PDF

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Publication number
EP2331743B1
EP2331743B1 EP09791420.4A EP09791420A EP2331743B1 EP 2331743 B1 EP2331743 B1 EP 2331743B1 EP 09791420 A EP09791420 A EP 09791420A EP 2331743 B1 EP2331743 B1 EP 2331743B1
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EP
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Prior art keywords
peptide
self
coating
assembling
poly
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EP09791420.4A
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German (de)
English (en)
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EP2331743A1 (fr
Inventor
Rudolf J. Koopmans
Amalia Aggeli
Eileen Ingham
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University of Leeds
Dow Global Technologies LLC
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University of Leeds
Dow Global Technologies LLC
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    • D—TEXTILES; PAPER
    • D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
    • D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
    • D06M15/00—Treating fibres, threads, yarns, fabrics, or fibrous goods made from such materials, with macromolecular compounds; Such treatment combined with mechanical treatment
    • D06M15/01—Treating fibres, threads, yarns, fabrics, or fibrous goods made from such materials, with macromolecular compounds; Such treatment combined with mechanical treatment with natural macromolecular compounds or derivatives thereof
    • D06M15/15—Proteins or derivatives thereof
    • D—TEXTILES; PAPER
    • D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
    • D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
    • D06M23/00—Treatment of fibres, threads, yarns, fabrics or fibrous goods made from such materials, characterised by the process
    • D06M23/005—Applying monomolecular films on textile products like fibres, threads or fabrics
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
    • Y10T428/2913—Rod, strand, filament or fiber
    • Y10T428/2933—Coated or with bond, impregnation or core

Definitions

  • the present invention generally relates to peptide-coated fibers, processes of fabricating said fibers, and articles incorporating said fibers.
  • New peptide-coated fibers are needed for applications where the peptide may add a beneficial function to, or beneficially modify a function of, the fibers, including applications where the fibers deliver the peptide to a site in need of a beneficial peptide activity.
  • fibers coated with a sequestering peptide are sought for catalyst support and air and liquid filtration applications among others.
  • Fibers coated with an anti-infective peptide are of interest for wound care, personal hygiene, filtration, and cleaning applications for instance.
  • such peptide-coated fibers are reusable.
  • anti-infective peptide-coated fibers are needed that may release from the coated fibers in response to a coating trigger, kill infectious organisms at a site in need of anti-infective activity, and then re-coat the fibers in response to another coating trigger to give recoated anti-infective peptide-coated fibers.
  • the present invention provides peptide-coated fibers, processes of fabricating said fibers, and articles incorporating said fibers.
  • the present invention is a peptide-coated fiber comprising a coating-receptive fiber and a peptide coating, the peptide coating being in reversible operative coating contact with the coating-receptive fiber; wherein the coating-receptive fiber has a diameter of 10 micrometers ( ⁇ m) or less and comprises a molecularly self-assembling (MSA) material selected from the grap comprising a poly(ester-amide), poly(ether-amide), poly(ester-urea), poly(ether-urea), poly(ester-urethone), and poly(ether-urethone), or a mixture thereof, and the peptide coating comprises at least one self-assembled peptide polymer, wherein each self-assembled peptide polymer comprises two or more self-assembling peptides and each self-assembling peptide is the same or different and independently comprises a self-assembly segment of from 2 to 59 amino acid residues.
  • MSA molecularly self-assembling
  • each self-assembling peptide independently further comprises one or two supplemental segments, each supplemental segment independently comprising 1 or more amino acid residues.
  • the supplemental segments are absent.
  • each supplemental segment independently comprises residuals from a protein expression of the self-assembling peptide.
  • the coating-receptive fiber has a diameter of 5 ⁇ m or less, more preferably less than 1000 nanometers (nm).
  • said peptide-coated fiber comprises a single layer coating comprising one or more self-assembled peptide polymers.
  • said peptide-coated fiber comprises two or more layer coatings independently comprising same or different self-assembled peptide polymers.
  • the present invention is an article comprised of at least one peptide-coated fiber of the first embodiment.
  • the present invention is a process of fabricating a peptide-coated fiber of the first embodiment, the process comprising the steps of: (a) contacting a coating-receptive fiber that has a diameter of 10 ⁇ m or less and comprises a MSA material selected from the grap comprising a poly(ester-amide), poly(ether-amide), poly(ester-urea), poly(ether-urea), poly(ester-urethone), and poly(ether-urethone), or a mixture thereof, to a medium comprising at least one self-assembled peptide polymer and a peptide-coating solvent, wherein said at least one self-assembled peptide polymer is dissolved in the peptide-coating solvent and contacts said coating-receptive fiber, wherein each self-assembled peptide polymer independently comprises two or more self-assembling peptides and each self-assembling peptide is the same or different and independently comprises a self-assembly segment of from 2 to 59 amino
  • the contacting step is allowed to proceed for a time (e.g., 1 hour) sufficient for at least partially coating the coating-receptive fiber.
  • the process further comprises a drying step of removing a substantial portion of the peptide-coating solvent from the peptide-coated fiber.
  • the present invention provides peptide-coated fibers, processes of fabricating said fibers, and articles comprising one or more said fibers.
  • the peptide-coated fiber of the first embodiment comprises a woven material or, more preferably, a non-woven material, e.g., a non-woven mat.
  • any lower limit of a range, or any preferred lower limit of the range may be combined with any upper limit of the range, or any preferred upper limit of the range, to define a preferred embodiment of the range.
  • the U.S. unit value controls.
  • a value given in a U.S. unit e.g., millimeters of mercury
  • a standard international unit e.g., kilopascals
  • the open-ended terms "comprising,” “comprises,” and the like may be replaced by the respective partially closed phrases “consisting essentially of,” consists essentially of,” and the like or the respective closed phrases “consisting of,” “consists of,” and the like.
  • a coating-receptive fiber useful in the present invention means a filament, including a fibril, having a diameter of 10 ⁇ m or less that is capable of receiving a peptide-coating comprising a self-assembled peptide polymer.
  • a fiber capable of receiving a peptide coating is of a diameter small enough so that the self-assembled peptide polymer is physically at least partially wrapped around the coating-receptive fiber (as discussed below), comprises chemical functional groups that interact with functional groups of the self-assembled peptide polymer as described below for "operative coating contact," or, preferably, a combination thereof.
  • a coating-receptive fiber useful in the present invention comprises a man-made material.
  • the man-made material preferably comprises an organic polymer material.
  • organic polymer materials are: polyesters such as poly(ethylene terephthalate) and poly(butylene terephthalate); polyamides such as nylon-6,6; poly(ester-amides); poly(ether-amides); poly(ester-ureas); poly(ether-ureas); poly(ester-urethanes); and poly(ether-urethanes).
  • the poly(ester-amide), poly(ether-amide), poly(ester-urea), poly(ether-urea), poly(ester-urethane), and poly(ether-urethane) are molecularly self-assembling (MSA) materials.
  • the coating-receptive fiber comprises a MSA material.
  • a MSA material means an oligomer or polymer that effectively forms larger associated or assembled oligomers and/ or polymers through the physical intermolecular associations of chemical functional groups. Without wishing to be bound by theory, it is believed that the intermolecular associations do not increase the molecular weight (Mn-Number Average molecular weight) or chain length of the self-assembling material and covalent bonds between said materials do not form. This combining or assembling occurs spontaneously upon a triggering event such as cooling to form the larger associated or assembled oligomer or polymer structures.
  • MSAs exhibit mechanical properties similar to some higher molecular weight synthetic polymers and viscosities like very low molecular weight compounds.
  • MSA organization self-assembly is caused by non-covalent bonding interactions, often directional, between molecular functional groups or moieties located on individual molecular (i.e. oligomer or polymer) repeat units (e.g. hydrogen-bonded arrays).
  • Non-covalent bonding interactions include: electrostatic interactions (ion-ion, ion-dipole or dipole-dipole), coordinative metal-ligand bonding, hydrogen bonding, ⁇ - ⁇ -structure stacking interactions, donor-acceptor, and/or van der Waals forces and can occur intra- and intermolecularly to impart structural order.
  • One preferred mode of self-assembly is hydrogen-bonding and this non-covalent bonding interactions is defined by a mathematical "Association constant", K(assoc) constant describing the relative energetic interaction strength of a chemical complex or group of complexes having multiple hydrogen bonds. Such complexes give rise to the higher-ordered structures in a mass of MSA materials.
  • a description of self assembling multiple H-bonding arrays can be found in " Supramolecular Polymers", Alberto Ciferri Ed., 2nd Edition, pages (pp) 157-158 .
  • a "hydrogen bonding array” is a purposely synthesized set (or group) of chemical moieties (e.g. carbonyl, amine, amide, hydroxyl. etc.) covalently bonded on repeating structures or units to prepare a self assembling molecule so that the individual chemical moieties preferably form self assembling donor-acceptor pairs with other donors and acceptors on the same, or different, molecule.
  • a "hydrogen bonded complex” is a chemical complex formed between hydrogen bonding arrays.
  • Hydrogen bonded arrays can have association constants K (assoc) between 10 2 and 10 9 M -1 (reciprocal molarities), generally greater than 10 3 M -1 .
  • the arrays are chemically the same or different and form complexes.
  • the molecularly self-assembling materials (MSA) suitable for melt-blowing presently include: molecularly self-assembling polyesteramides, copolyesteramide, copolyetheramide, copolyetherester-amide, copolyetherester-urethane, copolyether-urethane, copolyester-urethane, copolyester-urea, copolyetherester-urea and their mixtures.
  • Preferred MSA include copolyesteramide, copolyether-amide, copolyester-urethane, and copolyether-urethanes.
  • the MSA preferably has number average molecular weights, MW n (interchangeably referred to as M n ) (as is preferably determined by NMR spectroscopy) of 2000 grams per mole or more, more preferably at least about 3000 g/mol, and even more preferably at least about 5000 g/mol.
  • M n number average molecular weights
  • the MSA preferably has MW n 50,000 g/mol or less, more preferably about 20,000 g/mol or less, yet more preferably about 15,000 g/mol or less, and even more preferably about 12,000 g/mol or less.
  • the MSA material preferably comprises molecularly self-assembling repeat units, more preferably comprising (multiple) hydrogen bonding arrays, wherein the arrays have an association constant K (assoc) preferably from 10 2 to 10 9 reciprocal molarity (M -1 ) and still more preferably greater than 10 3 M -1 ; association of multiple-hydrogen-bonding arrays comprising donor-acceptor hydrogen bonding moieties is the preferred mode of self assembly.
  • the multiple H-bonding arrays preferably comprise an average of 2 to 8, more preferably 4-6, and still more preferably at least 4 donor-acceptor hydrogen bonding moieties per molecularly self-assembling unit.
  • Molecularly self-assembling units in preferred MSA materials include bis-amide groups, and bis-urethane group repeat units and their higher oligomers.
  • Preferred self-assembling units in the MSA material are bis-amides, bis-urethanes and bis-urea units or their higher oligomers.
  • a self-assembling unit comprises a poly(ester-amide), poly(ether-amide), poly(ester-urea), poly(ether-urea), poly(ester-urethane), or poly(ether-urethane), or a mixture thereof.
  • oligomers or polymers comprising MSA materials may simply be referred to herein as polymers, which includes homopolymers and interpolymers such as co-polymers, terpolymers, etc.
  • the MSA materials include "non-aromatic hydrocarbylene groups” and this term means specifically herein hydrocarbylene groups (a divalent radical formed by removing two hydrogen atoms from a hydrocarbon) not having or including any aromatic structures such as aromatic rings (e.g. phenyl) in the backbone of the oligomer or polymer repeating units.
  • non-aromatic hydrocarbylene groups are optionally substituted with various substituents, or functional groups, including but not limited to: halides, alkoxy groups, hydroxy groups, thiol groups, ester groups, ketone groups, carboxylic acid groups, amines, and amides.
  • non-aromatic heterohydrocarbylene is a hydrocarbylene that includes at least one non-carbon atom (e.g. N, O, S, P or other heteroatom) in the backbone of the polymer or oligomer chain, and that does not have or include aromatic structures (e.g., aromatic rings) in the backbone of the polymer or oligomer chain.
  • non-aromatic heterohydrocarbylene groups are optionally substituted with various substituents, or functional groups, including but not limited to: halides, alkoxy groups, hydroxy groups, thiol groups, ester groups, ketone groups, carboxylic acid groups, amines, and amides.
  • Heteroalkylene is an alkylene group having at least one non-carbon atom (e.g. N, O, S or other heteroatom) that, in some embodiments, is optionally substituted with various substituents, or functional groups, including but not limited to: halides, alkoxy groups, hydroxy groups, thiol groups, ester groups, ketone groups, carboxylic acid groups, amines, and amides.
  • a "cycloalkyl” group is a saturated carbocyclic radical having three to twelve carbon atoms, preferably three to seven.
  • a "cycloalkylene” group is an unsaturated carbocyclic radical having three to twelve carbon atoms, preferably three to seven.
  • Cycloalkyl and cycloalkylene groups independently are monocyclic or polycyclic fused systems as long as no aromatics are included.
  • Examples of carbocyclic radicals include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.
  • the groups herein are optionally substituted in one or more substitutable positions as would be known in the art.
  • cycloalkyl and cycloalkylene groups are optionally substituted with, among others, halides, alkoxy groups, hydroxy groups, thiol groups, ester groups, ketone groups, carboxylic acid groups, amines, and amides.
  • cycloalkyl and cycloalkene groups are optionally incorporated into combinations with other groups to form additional substituent groups, for example: "-Alkylene-cycloalkylene-, "-alkylene-cycloalkylene-alkylene-", “-heteroalkylene-cycloalkylene-”, and “-heteroalkylene-cycloalkyl-heteroalkylene” which refer to various non-limiting combinations of alkyl, heteroalkyl, and cycloalkyl.
  • oxydialkylenes e.g., diethylene glycol
  • groups derived from branched diols such as neopentyl glycol or derived from cyclo- hydrocarbylene diols such as Dow Chemical's UNOXOL® isomer mixture of 1,3- and 1,4-cyclohexanedimethanol
  • other non-limiting groups such -methylcylohexyl-, -methyl-cyclohexyl-methyl-, and the like.
  • Heterocycloalkyl is one or more cyclic ring systems having 4 to 12 atoms and containing carbon atoms and at least one and up to four heteroatoms selected from nitrogen, oxygen, or sulfur.
  • Heterocycloalkyl includes fused ring structures.
  • Preferred heterocyclic groups contain two ring nitrogen atoms, such as piperazinyl.
  • the heterocycloalkyl groups herein are optionally substituted in one or more substitutable positions.
  • heterocycloalkyl groups are optionally substituted with halides, alkoxy groups, hydroxy groups, thiol groups, ester groups, ketone groups, carboxylic acid groups, amines, and amides.
  • the MSA materials useful in the present invention are poly(ester-amides), poly(ether-amides), poly(ester-ureas), poly(ether-ureas), poly(ester-urethanes), and poly(ether-urethanes), and mixtures thereof that are described in United States Patent Number (USPN) US 6,172,167 , and applicant's co-pending PCT application numbers PCT/US2006/023450 , which was renumbered as PCT/US2006/004005 and published under PCT International Patent Application Number (PCT-IPAPN) WO 2007/099397 ; PCT/US2006/035201 , which published under PCT-IPAPN WO 2007/030791 ; PCT/US08/053917 ; PCT/US08/056754 ; and PCT/US08/065242 .
  • Preferred MS A materials are described below.
  • the molecularly self-assembling material comprises ester repeat units of Formula I: and at least one second repeat unit selected from the esteramide units of Formula II and III: and the ester-urethane units of Formula IV: wherein R is at each occurrence, independently a C 2 -C 20 non-aromatic hydrocarbylene group, a C 2 -C 20 non-aromatic heterohydrocarbylene group, or a polyalkylene oxide group having a group molecular weight of from about 100 to about 5000 g/mol.
  • the C 2 -C 20 non-aromatic hydrocarbylene at each occurrence is independently specific groups: alkylene-, -cycloalkylene-, -alkylene-cycloalkylene-, -alkylene-cycloalkylene-alkylene-(including dimethylene cyclohexyl groups).
  • these aforementioned specific groups are from 2 to 12 carbon atoms, more preferably from 3 to 7 carbon atoms.
  • the C 2 -C 20 non-aromatic heterohydrocarbylene groups are at each occurrence, independently specifically groups, non-limiting examples including: -hetereoalkylene-, -heteroalkylene-cycloalkylene-, -cycloalkylene-heteroalkylene-, or -heteroalkylene-cycloalkylene-heteroalkylene-, each aforementioned specific group preferably comprising from 2 to 12 carbon atoms, more preferably from 3 to 7 carbon atoms.
  • Preferred heteroalkylene groups include oxydialkylenes, for example diethylene glycol ( -CH 2 CH 2 OCH 2 CH 2 -O-).
  • R is a polyalkylene oxide group it preferably is a polytetramethylene ether, polypropylene oxide, polyethylene oxide, or their combinations in random or block configuration wherein the molecular weight (Mn-average molecular weight, or conventional molecular weight) is preferably about 250 g/ml to 5000, g/mol, more preferably more than 280 g/mol, and still more preferably more than 500 g/mol, and is preferably less than 3000 g/mol; in some embodiments, mixed length alkylene oxides are included.
  • Other preferred embodiments include species where R is the same C 2 -C 6 alkylene group at each occurrence, and most preferably it is -(CH 2 ) 4 -.
  • R 1 is at each occurrence, independently, a bond, or a C 1 -C 20 non-aromatic hydrocarbylene group. In some preferred embodiments, R 1 is the same C 1 -C 6 alkylene group at each occurrence, most preferably -(CH 2 ) 4 -.
  • R 2 is at each occurrence, independently, a C 1 -C 20 non-aromatic hydrocarbylene group. According to another embodiment, R 2 is the same at each occurrence, preferably C 1 -C 6 alkylene, and even more preferably R 2 is -(CH 2 ) 2 -, -(CH 2 ) 3 -, -(CH 2 ) 4 -, or -(CH 2 ) 5 -.
  • Ra is a C 2 -C 20 non-aromatic hydrocarbylene group, more Preferably a C 2 -C 12 alkylene: most preferred Ra groups are ethylene butylene, and hexylene -(CH 2 ) 6 -.
  • R N is piperazin-1,4-diyl.
  • both R 3 groups are hydrogen.
  • n is at least 1 and has a mean value less than 2.
  • polyesteramides of Formula I and II, or Formula I, II, and III particularly preferred materials are those wherein R is -(C 2 -C 6 )- alkylene, especially -(CH 2 ) 4 -, Also preferred are materials wherein R 1 at each occurrence is the same and is C 1 -C 6 alkylene, especially -(CH 2 ) 4 -. Further preferred are materials wherein R 2 at each occurrence is the same and is -(C 1 -C 6 )- alkylene, especially -(CH 2 ) 5 - alkylene.
  • the polyesteramide according to this embodiment preferably has a number average molecular weight (Mn) of at least about 4000, and no more than about 20,000. More preferably, the molecular weight is no more than about 12,000.
  • the invention encompasses all possible distributions of the w , x , y , and z units in the copolymers, including randomly distributed w , x , y and z units, alternateatingly distributed w , x , y and z units, as well as partially, and block or segmented copolymers, the definition of these kinds of copolymers being used in the conventional manner as known in the art. Additionally, there are no particular limitations in the invention on the fraction of the various units, provided that the copolymer contains at least one w and at least one x , y , or z unit.
  • the mole fraction of w to ( x + y + z) units is between about 0.1:0.9 and about 0.9:0.1. In some preferred embodiments, the copolymer comprises at least 15 mole percent w units, at least 25 mole percent w units, or at least 50 mole percent w units.
  • the number average molecular weight (M n ) of the MSA material useful in the present invention is between 1000 g/mol and 30,000 g/mol, inclusive. In some embodiments, M n of the MSA material is between 2,000 g/mol and 20,000 g/mol, inclusive, preferably 5,000 g/mol to 12,000 g/mol. In more preferred embodiments, M n of the MSA material is less than 5,000 g/mol. Thus, in some more preferred embodiments, M n of the MSA material is at least about 1000 g/mol and 4,900 g/mol or less, more preferably 4,500 g/mol or less.
  • viscosity of a melt of a preferred MSA material is characterized as being Newtonian over the frequency range of 10 -1 to 10 2 radians per second (rad./s.) at a temperature from above a melting temperature T m up to about 40 degrees Celsius (°C) above T m , preferably as determined by differential scanning calorimetry (DSC).
  • preferred MSA materials exhibit Newtonian viscosity in the test range frequency at temperatures above 100 °C, more preferably above 120°C and more preferably still at or above 140 °C and preferably less than 300 °C, more preferably less than 250 °C and more preferably still less than 200 °C.
  • Newtonian has its conventional meaning; that is, approximately a constant viscosity with increasing (or decreasing) shear rate of a (MSA) material at a constant testing temperature.
  • the MSA materials preferably having M n less than 5,000 g/mol, advantageously possess low melt viscosities useful for high output (relative to traditional high polymer electrospinning) fiber electrospinning and utilities in submicron-fiber form.
  • the MSA materials having M n of about 7,000 g/mol or higher are particularly useful for melt blowing.
  • the zero shear viscosity of a preferred MSA material is in the range of from 0.1 Pa.s. to 1000 Pa.s., preferably from 0.1 Pa.s. to 100 Pa.s., more preferably from 0.1 to 30 Pa.s., still more preferred 0.1 Pa.s. to 10 Pa.s., between the temperature range of 180 °C and 220 °C, e.g., 180 °C and 190 °C.
  • the viscosity of a melt of a MSA material useful in the present invention is less than 100 Pa.s. at from above T m up to about 40 °C above T m .
  • the viscosity of one of the preferred MSA materials is less than 100 Pa.s. at 190 °C, and more preferably in the range of from 1 Pa.s. to 50 Pa.s. at 150 °C to 170 °C.
  • the glass transition temperature of the MSA material is less than 20 °C.
  • the melting point is higher than 60 °C.
  • Preferred MSA materials exhibit multiple glass transition temperatures T g .
  • the MSA material has a T g that is higher than -80 °C.
  • the MSA material has a T g that is higher than -60 °C.
  • the tensile modulus of one preferred group of MSA materials is preferably from 4 megapascals (MPa) to 500 MPa at room temperature, preferably 20 °C. Tensile modulus testing is well known in the polymer arts.
  • the torsional (dynamic) storage modulus of MSA materials useful in the invention is 12 MPa, more preferably at least 50 MPa, still more preferably at least 100 MPa, all at 20 °C.
  • the storage modulus is 400 MPa or lower, more preferably 300 MPa or lower, still more preferably 250 MPa or lower, or still more preferably about 200 MPa or lower, all at 20 °C.
  • polydispersities of substantially linear MSA materials useful in the present invention is 4 or less, more preferably 3 or less, still more preferably 2.5 or less, still more preferably 2.2 or less.
  • the polymers described herein are modified with, for example and without limitation thereto, other polymers, resins, tackifiers, fillers, oils and additives (e.g. flame retardants, antioxidants, pigments, dyes, and the like).
  • Coating-receptive fibers may be fabricated by any known method including, for example, solution spinning, fiber drawing, textile spinning, spun bonding, electrospinning (e.g., solution or melt electrospinning), electroblowing, and melt blowing.
  • processing conditions for these methods are adjusted to produce coating-receptive fibers, without beading, of different average diameters including submicron average-diameter coating-receptive fibers.
  • coating-receptive fibers are produced at elevated temperatures, allowing for production of aseptic coating-receptive fibers (i.e., coating-receptive fibers that are essentially free of living microorganisms).
  • the MSA material is characterized by having, when measured as a melt, a viscosity, tensile modulus, or torsional storage modulus as described above.
  • Devices for fabricating fibers include electrospinning devices, melt blowing devices, melt extruding devices, and the like.
  • such devices include one or more collectors for collecting the fibers.
  • suitable collectors are webs, foils, films, papers, fabrics, wovens, and nonwovens.
  • Collectors may comprise inorganic or organic materials such as, for example, wood or, preferably glass, polymers, metals, papers ceramics, and combinations thereof.
  • a collector comprises a non-woven web scaffolding useful in medical applications (e.g., as a bandage).
  • Some embodiments of the process of the third embodiment employ two or more collectors, each collector collecting at least one peptide-coated fiber.
  • a typical electrospinning apparatus for use in preferred embodiments of the present invention includes three primary components: a high voltage power supply, a spinneret, and a conductor (e.g., a grounded conductor or charged conductor).
  • the charged conductor may have a polarity opposite to the polarity of the spinneret (e.g., spinneret may have positive charge and charged conductor may have negative charge).
  • such an electrospinning apparatus further includes one or more collectors. Collectors for electrospinning are grounded or ungrounded.
  • the apparatus further includes an ungrounded collector that is placed in front of the conductor and optionally is or is not in physical contact therewith.
  • the spinneret is a spin electrode that allows for extracting fibers by way of an electric field.
  • the spinneret is a syringe, a cylinder (e.g., a cylinder rotating in a solution), screen, wire, a capillary device, or a conductive surface that is connected to a feeding system for introducing a material (e.g., a solution or melt) of the fiber forming self-assembling material, and optionally is or is not heated and does and does not include hot air jets.
  • a preferred system uses a pump to control the flow of the material out of, for example, a syringe nozzle allowing the material to form a Taylor cone.
  • the electrospinning device comprises at least one electrode (e.g., spinneret or cylinder), at least one conductor (e.g., a grounded conductor or a conductor charged with opposite polarity compared to polarity of a charge of the electrode), a source of voltage (e.g., a power supply), and, optionally, a collector, wherein the electrode(s) independently is in operative electricity communication with the source of voltage and with the conductor.
  • the electrode is in physical contact with the solution or melt of self-assembling material, which solution or melt preferably is in operative fluid communication between a source thereof and the electrode.
  • the process further comprises a step of collecting the fibers on a grounded conductor or, more preferably, on a collector.
  • the collector may or may not be grounded and may or may not be charged with opposite polarity compared to polarity of a charge of an electrode of the electrospinning device.
  • Preferred electrospinning devices are those that are marketed commercially as being useful for electrospinning.
  • Use of commercially available electrospinning devices such as those available from NanoStaticsTM, LLC, Circleville, Ohio, USA; and Elmarco s.r.o., Liberec, Czech Republic (e.g., using NanospiderTM technology), are more preferred.
  • Preferred self-assembling materials useful in the present invention are solution electrospun into fibers, including submicron diameter fibers, from solutions having viscosities, in a temperature range of from 20 °C to 50 °C, preferably at 20 °C, from about 0.001 Pa.s. to about 0.5 Pa.s, preferably at least about 0.005 Pa.s., more preferably at least about 0.01 Pa.s.
  • the self-assembling material is present in the solution at a concentration of from about 4 weight percent to about 30 weight percent, preferably from about 6 weight percent to about 25 weight percent. Consequently, higher fiber production rates are possible with the preferred materials for a given solution electrospinning device than have been achieved with conventional polymers that self-associate substantially via an entanglement mechanism.
  • Preferred solutions are characterized as being capable of being electrospun from a needle at a high production rate, preferably at a rate greater than 4.5 milliliters per hour, more preferably at a rate greater than 10 mL/hour. This characterization of the solution does not limit the electrospinning device to a particular type thereof.
  • the combination of the low solution viscosities of the MSA materials of the invention coupled with the ability to electrospin the MSA materials at a variety of temperatures means that various concentrations, including low solution concentrations and high solution concentrations, of the MSA materials are easily used for electrospinning. Unless otherwise stated, there is therefore no particular limitation on the solution concentration of the self-assembling materials for solution electrospinning and any concentration that is less than 100 weight percent (wt%) and greater than 0 wt% is encompassed. In other preferred embodiments, the concentration is increasingly preferably 75 weight percent or less, 50 weight percent or less, about 30 weight percent or less, or 25 weight percent or less.
  • the concentration is at least about 0.1 weight percent, preferably at least about 2 weight percent, more preferably at least about 4 weight percent, and further more preferably at least about 6 weight percent, at room temperatures. Particularly preferred is a concentration of about 12 weight percent at room temperature. In still another embodiment, the preferred concentration is from about 4 weight percent to about 30 weight percent at room temperature, more preferably from about 6 weight percent to about 25 weight percent. In still another preferred embodiment, the concentration of self-assembling material is from greater than 40 weight percent to 99.9 weight percent, more preferably at least about 60 weight percent, still more preferably at least about 75 weight percent, still more preferably at least about 90 weight percent, even more preferably at least about 98 weight percent (up to less than 100 weight percent). More preferably, the concentration of self-assembling material is from greater than 40 weight percent to 99.9 weight percent and the solution electrospinning process preferably further comprises a preliminary step of heating the self-assembling material and solution-electrospinning solvent to give the solution.
  • weight percent concentration of a molecularly self-assembling material in the solution-electrospinning solvent is calculated by dividing the weight of the molecularly self-assembling material dissolved in the solvent by the sum of the weight of the molecularly self-assembling material dissolved in the solvent plus weight of the solvent. Weight of any undissolved molecularly self-assembling material is not counted in determining said weight percent concentration.
  • the polymer solution is fed into or onto the spinneret from, for example, a syringe at a constant and controlled rate using a metering pump.
  • a high voltage (1 kilovolt (kV) to 120 kV, preferably 1 kV to 100 kV, and more preferably 1 kV to 50 kV) is applied and a portion of the polymer solution, preferably in the form of a droplet, at the nozzle (e.g., needle) of the syringe becomes highly electrified.
  • the portion e.g., droplet
  • a fine jet in some embodiments two or more such jets, of polymer develops.
  • the fine polymer jet is drawn towards the grounded conductor which is placed opposing the spinneret. While being drawn towards the grounded conductor, the solution-electrospinning solvent at least partially dissipates (e.g., at least partially phase separates, evaporates, or a combination thereof) and the jet solidifies into fibers. Preferably, the solution-electrospinning solvent is substantially completely dissipated (i.e., lost) from the fibers.
  • Substantially complete dissipation of the solvent from the fibers may occur before, during, or after the fibers are deposited and may comprise part of a solution electrospinning unit operation or a separate unit operation (e.g., a drying operation that may or may not be in direct communication with the solution electrospinning unit operation).
  • the fibers are deposited on a collector that is placed in front of the conductor.
  • fibers are deposited on the collector as a randomly oriented, non-woven mat or individually captured and wound-up on a roll. The fibers are subsequently stripped from the collector if desired.
  • a charged conductor opposite polarity to that of electrode is employed instead of the grounded conductor.
  • the spinneret is operated at about 20 °C or ambient temperature, the spin electrode is maintained at the same temperature or temperature at which the molecularly self-assembling material has sufficiently low viscosity to allow thin fiber formation.
  • the spinneret is generally heated up to about 300 °C and the surrounding environmental temperature optionally is maintained at about similar temperatures using hot air.
  • the spinneret is generally heated up to about 300 °C and the surrounding environmental temperature optionally, is maintained at about room temperature (i.e., from about 20 °C to 30 °C).
  • the applied voltage is generally about 1 kV) to 120 kV, preferably about 1 kV to 100 kV, more preferably 1 kV to 50 kV.
  • the electrode gap (the gap between spin electrode and conductor) is generally between about 3 centimeters (cm) and about 50 cm, preferably between about 3 cm and about 40 cm.
  • the fibers are fabricated at about ambient pressure (e.g., 1.0 atmosphere), although the pressure may be higher or lower depending upon the particular operating conditions employed such as solvent(s), concentrations of solutions of self-assembling materials, and temperatures.
  • Preferred electrospinning devices are those that are marketed commercially as being useful for solution electrospinning.
  • a preferred solution-electrospinning solvent is (monohalo to perhalo)(C 1 -C 6 )alkyl; R 1 C(O)OR 2 ; R 1 C(O)NR 3 R 4 ; R 3 OR 4 ; R 5 C(O)R 6 ; or a mixture thereof, wherein each halo independently is fluoro or chloro, each R 1 and R 2 independently is H or (C 1 -C 3 )alkyl, each R 3 and R 4 independently is H or (C 1 -C 3 )alkyl or R 3 and R 4 taken together form a (C 2 -C 6 )alkylene, and each R 5 and R 6 independently is (C 1 -C 3 )alkyl or R 5 and R 6 taken together form a (C 2 -C 6 )alkylene.
  • a more preferred solvent is chloroform, methanol, water, formic acid, alcohols (e.g., R 3 OR 4 wherein R 3 is (C 1 -C 3 )alkyl and R 4 is H), N,N-dimethylformamide, tetrahydrofuran, 1,2-dichloroethane, ethyl acetate, methylethylketone, or mixtures thereof. Still more preferred are chloroform and formic acid.
  • (C 1 -C 3 )alkyl means methyl, ethyl, 1-propyl, or 2-propyl.
  • (C 2 -C 6 )alkylene means a straight or branched hydrocarbon diradical of 2 to 6 carbon atoms.
  • the (C 1 -C 3 )alkyl and (C 2 -C 6 )alkylene independently are unsubstituted or substituted with one or more substituents halides, alkoxy groups (e.g., (C 1 -C 3 )alkoxy), hydroxy, thiol (i.e., -SH), carboxylic ester groups (e.g., -C(O)OR 2 ), ketone groups (e.g., -C(O)R 6 ;), carboxylic acid (i.e., -COOH), amines (e.g., -NR 3 R 4 ), and amides (e.g., -C(O)NR 3 R 4 ), wherein R 2 , R 3 , R 4 , and R 6 are unsubstituted versions of the groups as defined herein for the electrospinning solvents.
  • substituents halides alkoxy groups (e.g., (C 1 -C 3 )al
  • a surfactant, salt, and other material is added to the electrospinning solution to modify one or more of the operating characteristics (e.g., viscosity, conductivity (or resistivity), and surface tension) of the solution.
  • these additives include, but are not limited to, sodium dodecyl sulfate, pyridinium formate, inorganic salt, poly(ethylene glycol), triethyl benzyl ammonium chloride, aliphatic poly(propylene oxide)- poly(ethylene oxide) ether, nanoclay (laponite) and combinations thereof.
  • the coating-receptive fibers comprising a MSA material that are prepared by the solution electrospinning process described above generally have an average diameter of about 1500 nm or less, more preferably about 800 nm or less, and more preferably about 600 nm or less.
  • the average diameter of the coating-receptive fibers is at least 10 nm, more preferably at least 100 nm, still more preferably at least 200 nm.
  • the coating-receptive fibers have an average diameter of about 10 nm to about 1500 nm, more preferably about 200 to about 600 nm. Particularly preferred are coating-receptive fibers with an average diameter of about 300 nm.
  • the solution electrospun fibers are characterized as having beading. More preferably, the beaded fibers have an average diameter of about 10 nm to about 1500 nm.
  • the term "beading" means one or more portions of a fiber characterized by approximately spherical- or ellipsoid-shaped thickening. The geometry of the actual bead structures may be distorted in various ways. Where there are two or more such portions along the fiber, the portions are continuous (i.e., partially merged portions), discontinuous (i.e., separated by a fiber segment that lacks beading), or a combination thereof. Beading is distinguished from non-specific fiber size variations by SEM.
  • the MSA material in melted form is fed into or onto the spinneret from, for example, the syringe at a constant and controlled rate using a metering pump.
  • a high voltage e.g., 1 kV to 120 kV
  • the droplet forms a Taylor cone, and a fine jet of polymer develops.
  • the fine polymer jet is drawn to the conductor (e.g., a grounded conductor), which is placed opposing the spinneret.
  • the jet cools and hardens into coating-receptive fibers.
  • the fibers are deposited on a collector that is placed in front of the conductor.
  • fibers are deposited on the collector as a randomly oriented, non-woven mat or individually captured and wound-up on a roll. The fibers are subsequently stripped from the collector if desired.
  • a charged conductor opposite polarity to that of electrode is employed instead of the grounded conductor.
  • the spinneret is generally heated up to about 300 °C, the spin electrode temperature is maintained at about 10 °C or higher (e.g., up to just below a decomposition temperature of the MSA material or up to about 150 °C higher) above the melting point or temperature at which the MSA material has sufficiently low viscosity to allow thin coating-receptive fiber formation, and the surrounding environmental temperature is unregulated or, optionally, heated (e.g., maintained at about similar temperatures using hot air).
  • the spinneret is generally heated up to about 300 °C and the surrounding environmental temperature optionally is maintained at about room temperature (i.e., from about 20 °C to 30 °C).
  • the applied voltage is generally about 1 kV to 120 kV, preferably 1 kV to 80 kV.
  • the electrode gap (the gap between spin electrode and collector) is generally between about 3 cm and about 50 cm, preferably about 3 cm and about 19 cm.
  • the coating-receptive fibers are fabricated at about ambient pressure (e.g., 1.0 atmosphere) although the pressure can be higher or lower.
  • Preferred electrospinning devices are those that are marketed commercially as being useful for melt electrospinning. Use of commercially available melt electrospinning device such as NS Lab M device, Elmarco s.r.o., Liberec, Czech Republic (e.g., using NanospiderTM technology), are more preferred.
  • the coating-receptive fibers comprising a MSA material that are prepared by a melt electrospinning process described above generally have an average diameter of about 1000 nm or less, more preferably about 800 nm or less, and more preferably about 600 nm or less.
  • the average diameter of the coating-receptive fibers is at least 100 nm, more preferably at least 200 nm.
  • the coating-receptive fibers have an average diameter of about 30 nm to about 1000 nm, more preferably about 200 nm to about 600 nm.
  • the coating-receptive fibers have an average diameter of about 50 nm to about 1000 nm.
  • coating-receptive fibers are fabricated with diameters as low as about 30 nm. Particularly preferred are coating-receptive fibers with average diameters of about 200 nm to 300 nm.
  • a melt electrospinning process described above produces coating-receptive fibers comprising a MSA material without beading.
  • a melt blowing device typically comprises at least one die block having a portion that functions as a die tip; at least one gas knife assembly; a source of a stretch gas stream; and a collector, wherein the source of a stretch gas stream independently is in operative fluid communication with the gas knife assembly and the die tip.
  • the die tip defines at least one, preferably a plurality of, apertures through which a melt of a material to be melt blown passes.
  • a source of the melt is in operative fluid communication with the apertures of the die tip.
  • useful stretch gases are air, nitrogen, argon, helium, and a mixture of any two or more thereof.
  • the stretch gas is air, nitrogen, or a mixture thereof; more preferably the stretch gas is air.
  • melt blowing device is an Oerlikon Neumag Meltblown TechnologyTM system (Oerlikon Heberlein Wattwil AG, Switzerland).
  • the stretch gas is air sourced from a compressed air chamber and temperature of the stretch gas is measured in the compressed air chamber.
  • the invention herein may use any melt blowing system but preferably uses specialized process melt-blowing systems produced by Hills, Inc. of West Melbourne, Florida 32904. See e.g. United States Patent 6,833,104 B2 , and WO 2007/121458 A2 . See also www.hillsinc.net/technology.shtml and www.hillsinc.net/nanomeltblownfabric.shtml and the article " Potential of Polymeric Nanofibers for Nonwovens and Medical Applications” by Dr John Hagewood” J. Hagewood, LLC, and Ben Shuler, Hills, Inc, published in the 26 February 2008 Volume of Fiberjournal.com.
  • Preferred dies have very large Length/Diameter flow channel ratios (L/D) in the range of greater than 20/1 to 1000/1, preferably greater than 100/1 to 1000/1, including for example, but not limited to, L/D values 150/1, 200/1,250/1, 300/1 and the like so long as there is sufficient polymer back pressure for even polymer flow distribution.
  • the die spinholes are typically on the order of 0.05 to 0.2 mm in diameter.
  • average fiber diameter for a plurality of fibers is determined by processing a SEM image thereof with, for example, a QWin image analysis system (Leica Microsystems GmbH, 35578 Wezlar, Germany).
  • the coating-receptive fiber(s) useful in the present invention is used in a process of the third embodiment of the present invention in woven or non-woven form and in the form of a fabric, including a woven fabric, or article.
  • the term "medium” means a solution of a self-assembling peptide or a self-assembled peptide polymer, or a combination thereof, essentially completely dissolved in a peptide-coating solvent or a suspension comprising said solution and an undissolved amount of said self-assembling peptide, self-assembled peptide polymer, or combination thereof suspended wherein.
  • said undissolved amount is 10 wt% or less, more preferably 5 wt% or less, still more preferably 2 wt% or less, even more preferably less than 1 wt% of the total amount of said self-assembling peptide, self-assembled peptide polymer, or combination thereof.
  • the coating-receptive fiber(s) useful in the present invention are employed in a process of the third embodiment, the process employing a device for fabricating fibers that preferably includes a collector as described above, the process further comprising steps for fabricating the coating-receptive fiber(s), wherein the medium comprising at least one self-assembled peptide polymer and a peptide-coating solvent is contacted to the coating-receptive fiber before the coating-receptive fiber contacts the collector.
  • the process of fabricating a peptide-coated fiber comprises: (i) providing a melt of a self-assembling material or providing a solution of a self-assembling material and a solution-electrospinning solvent; (ii) either feeding the solution into an electrospinning device comprising at least one electrode, at least one conductor, a source of voltage, and a collector, wherein the electrode(s) independently is in operative electricity communication with the source of voltage and with the conductor, feeding the melt into the electrospinning device, or feeding the melt into a melt blowing device comprising at least one die block having a portion that functions as a die tip, at least one gas knife assembly, a source of a stretch gas stream, and a collector, wherein the source of a stretch gas stream independently is in operative fluid communication with the gas knife assembly and the die tip; (iii) either applying a voltage to the electrospinning device such that the solution of the self-assembling material and the solution-electrospinning solvent is drawn and a jet
  • a "peptide-coating solvent” means any liquid suitable for at least partially dissolving a plurality of self-assembling peptides. Preferably, each self-assembling peptide is fully dissolved in the solvent. Ideally, the peptide-coating solvent is chemically compatible with a coating-receptive fiber (i.e., at most the solvent dissolves or otherwise removes less than 5 wt%, preferably less than 1 wt%, more preferably less than 0.2 wt% of the fiber during a fiber-coating process of the third embodiment).
  • polar aprotic solvents e.g., dimethylsulfoxide (DMSO), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), tetrahydrofuran (THF), and ethyl acetate
  • polar protic solvents such as water, ethanol, methanol, acetic acid, and formic acid
  • the peptide-coating solvent comprises purified water (e.g., deionized or distilled water), acidic water (i.e., water having a pH less than 7, preferably by virtue of containing inorganic acid(s) such as hydrochloric acid), basic water (i.e., water having a pH greater than 7, preferably by virtue of containing inorganic base(s) such as sodium hydroxide), ionic water (e.g., water containing dissolved salt such as sodium chloride), 1,1,1,3,3,3-hexafluoropropan-2-ol.
  • purified water e.g., deionized or distilled water
  • acidic water i.e., water having a pH less than 7, preferably by virtue of containing inorganic acid(s) such as hydrochloric acid
  • basic water i.e., water having a pH greater than 7, preferably by virtue of containing inorganic base(s) such as sodium hydroxide
  • ionic water e.g.,
  • a substantial portion of peptide-coating solvent is removed from a peptide-coated fiber in contact therewith by, for example, evaporation (under ambient or non-ambient (higher or lower) temperatures, pressures, or both), washing with a different peptide-coating solvent or other liquid (e.g., a liquid suitable for further processing of said peptide-coated fiber), blotting, spinning (e.g., centrifuging), blowing (including blowing with a heated gas), suction, freeze-drying, or a combination thereof.
  • Removing a "substantial portion" of said solvent from said peptide-coated fiber gives a resulting dried peptide-coated fiber wherein said solvent accounts for less than 10 wt%, preferably less than 5 wt%, more preferably less than 2 wt%, even more preferably less than 1 wt% of a weight of said dried peptide-coated fiber.
  • Each self-assembled peptide polymer independently comprises a plurality (i.e., 2 or more) of self-assembling peptides.
  • the self-assembling peptides are the same or different and each self-assembling peptide independently comprises a self-assembling segment of from 2 to 59 amino acid residues and, optionally, one or two supplemental segments each independently comprising 1 or more amino acid residues.
  • the self-assembly segment being covalently bonded to the supplemental segment(s), preferably each via a peptide bond (i.e., preferably an amide bond, that is a -C(O)-N ⁇ bond).
  • each supplemental segment comprises 2,000 amino acid residues or fewer, more preferably 1,000 amino acid residues or fewer, still more preferably 500 amino acid residues or fewer, even more preferably 250 amino acid residues or fewer.
  • the self-assembling peptides are the same or different and are capable of organizing with each other into said self-assembled peptide polymer, which is further described below.
  • the self-assembling peptides of the plurality thereof are the same. In other aspects of the first embodiment, at least two of the self-assembling peptides of the plurality thereof are different.
  • self-assembling peptides useful in the present invention preferably comprise self-assembling segments comprising 40 or fewer amino acid residues, more preferably 38 or fewer such residues; or still more preferably 30 or fewer such residues; and the self-assembling peptides preferably comprise 4 or more such residues, more preferably 7 or more such residues, or still more preferably 10 or more such residues.
  • the self-assembling segments preferably comprise about 11, about 24, about 27, or about 37 such residues.
  • amino acid residues useful in the present invention are derived from non-naturally occurring (i.e., not found in proteins in nature) amino acids such as, for example, levorotary- (L-) form of ornithine (Orn) and those non-naturally occurring amino acids recited in table 3 of USPAPN US 2006/0121083 , which table 3
  • non-naturally occurring amino acids include dextrorotary- (D-) forms and chemically modified forms of naturally occurring L-amino acids.
  • Preferred chemically-modified forms of such an amino acid residue include acyl-modified amino group (e.g., acetylation of an - NH 2 of an N-terminal amino acid residue to form CH 3 C(O)N(H)-) and an amine-modified carboxyl group (e.g., -C(O)NH 2 ).
  • acyl-modified amino group e.g., acetylation of an - NH 2 of an N-terminal amino acid residue to form CH 3 C(O)N(H)-
  • an amine-modified carboxyl group e.g., -C(O)NH 2
  • the amino acid residues are derived from the following naturally occurring (i.e., found in proteins in nature) L-amino acids (conventional three letter and single letter codes): L-alanine (Ala; A), L-arginine (Arg; R), L-asparagine (Asn; N), L-aspartic acid (Asp; D), L-cysteine (Cys; C), L-glutamine (Gln; Q), L-glutamic acid (Glu; E), glycine (Gly; G), L-histidine (His; H), L-isoleucine (Ile; I), L-leucine (Leu; L), L-lysine (Lys; K), L-methionine (Met; M), L-phenylalanine (Phe; F), L-proline (Pro; P), L-serine (Ser; S), L-threonine (Thr; T), L-tryptophan (Trp; W
  • Self-assembling peptides useful in the present invention preferably are prepared by a number of conventional methods such as, for example, classical peptide synthesis comprising liquid-phase or solid-phase coupling of amino acids and classical protein expression methods.
  • Systems useful for protein expression of the self-assembling peptides include bacterial, yeast, baculovirus/insect, and mammalian expression systems.
  • the self-assembling peptides prepared by peptide synthesis preferably lack supplemental segment(s).
  • Supplemental segments typically derive from residuals of protein expression of the self-assembling peptides.
  • the supplemental segment(s) are cleaved from a self-assembling segment to give a self-assembling peptide consisting essentially of the self-assembling segment.
  • multi-segment self-assembling peptides comprising the self-assembling segments and the supplemental segments.
  • Such multi-segment self-assembling peptides may be cheaper to prepare than self-assembling peptides consisting essentially of self-assembling segments.
  • PCT-IPAPNs WO 96/31528 ; WO 02/081104 ; and WO 2004/007532 and their respective U.S. family members USPAPN: US 2002/0132974 ; US 2004/0235048 ; and US 2006/0154852 .
  • Other preferred self-assembling peptides useful in the present invention are described below.
  • US 2002/0132974 generally relates to peptides that self assemble to form ⁇ -sheet tape-like polymers comprised of monomers that are the self-assembling peptides.
  • the self-assembling peptides comprise from 4 to 40 amino acid residues, more preferably from 20 to 30 amino acid residues, still more preferably 27, 24, or 21 amino acid residues.
  • each of the self-assembling peptides of SEQ ID NOS: 1 to 9 self assemble to form ⁇ -sheet, tape-like self-assembled peptide polymers comprising complimentarily-bonded, anti-parallel arranged, homopeptide polymers.
  • US 2004/0235048 generally relates to coated substrates comprising a substrate and peptides that self assemble to form ⁇ -sheet tape-like polymers, wherein each substrate has a surface in operative coating contact with one or more layers of the ⁇ -sheet tape-like polymers.
  • Each layer of ⁇ -sheet tape-like polymer preferably is substantially parallel to the surface of the substrate and is essentially one molecule in thickness.
  • the thickness of each layer is typically from about 0.5 nanometers (nm) to about 2 nm.
  • the thickness of each layer is up to about 5 nm, depending on length of side chains of the non-naturally occurring amino acids.
  • US 2006/0154852 generally relates to peptides that self assemble to form, depending on conditions employed, ⁇ -sheet tape-like polymers (tapes), ribbons comprised of two stacked tapes, fibrils comprised of a plurality of ribbons stacked together, or peptide fibers comprised of entwined fibrils.
  • the self-assembling peptides comprise from 7 to 30 amino acid residues, more preferably 8 to 12 such residues, still more preferably 10 or 11 such residues, even more preferably 11 such residues.
  • SEQ ID NOS: 9 to 15 which have the sequence listings set forth below in Table 2.
  • Table 2 SEQ ID NO: Sequence Listing* 9 CH 3 C(O)-Gln Gln Arg Gln Gln Gln Gln Gln Glu Gln Gln-NH 2 10 CH3C(O)-Gln Gln Arg Phe Gln Trp Gln Phe Glu Gln Gln-NH 2 11 CH 3 C(O)-Gln Gln Arg Phe Glu Trp Glu Phe Glu Gln Gln-NH 2 12 CH3C(O)-Gln Gln Orn Phe Orn Trp Orn Phe Gln Gln Gln Gln-NH 2 13 CH 3 C(O)-Gln Gln Arg Phe Orn Trp Orn Phe Glu Gln Gln-NH 2 14 CH 3 C(O)-Gln Gln Gln Gln-NH 2 14 CH
  • the self-assembling peptides of SEQ ID NOS: 9 to 15 self assemble to form ⁇ -sheet tape-like self-assembled peptide polymers, ribbons comprised of two stacked said tape-like self-assembled peptide polymers, fibrils comprised of a plurality of said ribbons stacked together, or peptide fibers comprised of entwined said fibrils.
  • the ⁇ -sheet tape-like self-assembled peptide polymers include complimentarily-bonded, anti-parallel arranged, homopeptide polymers comprised of any one of SEQ ID NOS: 9 to 15 and complimentarily-bonded, anti-parallel arranged, alternating peptide copolymers comprised of any two complimentary peptides of SEQ ID NOS: 9 to 15 (e.g., complimentary peptides of SEQ ID NOS: 11 and 12).
  • self-assembling peptides useful in the present invention are those that form ⁇ -sheet tape-like self-assembled peptide polymers in an aqueous medium and comprise 3 or more polar/neutral amino acid residues and a plurality of chargeable amino acid residues (total number of amino acid residues being within the limits described herein).
  • the self-assembling peptides are comprised of 11 amino acid residues, preferably a ratio of chargeable amino acid residues to polar/neutral amino acid residues is from 1:11 to 4:11, preferably 3:11 or 4:11. More preferably, the self-assembling peptides are complimentarily-bonded, anti-parallel arranged, alternating peptide copolymers.
  • complimentarity of any two complimentary self-assembling peptides comprising said alternating peptide copolymers originates from opposite charges being present at a particular pH employed, e.g., at the pH employed, there is a net positive charge on one of self-assembling peptides and a net negative charge on the other one of self-assembling peptides.
  • Polar/neutral amino acid residues are the same or different and each residue independently and preferably is a residue of glutamine, serine, asparagine, ornithine, cysteine, lysine, histidine, glutamic acid, or threonine.
  • Chargeable amino acid residues include those internal (in a self-assembling peptide) residues that are positively charged at a pH of less than or equal to 7 (i.e., neutral pH), e.g., charged somewhere in a range of pH 2 to pH 7, and those residues that are negatively charged at a pH of greater than or equal to 7, e.g., charged somewhere in a range of pH 7 to pH 13, and those residues that are both positively and negatively charged.
  • Chargeable amino acid residues are the same or different and each residue independently and preferably is a residue of arginine, aspartic acid, cysteine, glutamic acid, histidine, lysine, ornithine, tryptophan, or tyrosine.
  • apolar amino acid residues are phenylalanine, valine, leucine, isoleucine, and methionine.
  • an internal tryptophan residue is apolar at or below neutral pH.
  • the self-assembling peptide of SEQ ID NO: 9 comprises a chargeable amino acid residue
  • the self-assembling peptides of SEQ ID NOS: 10, 11, 12, and 13 comprise from 1 to 3 chargeable amino acid residues
  • the self-assembling peptides of SEQ ID NOS: 14 and 15 comprise 3 or more chargeable amino acid residues.
  • SEQ ID NOS: 16 and 17 which have the sequence listings set forth below in Table 3.
  • Table 3 SEQ ID NO: Sequence Listing* 16 CH 3 C(O)-Ser Ser Arg Phe Glu Trp Glu Phe Glu Ser Ser-NH 2 17 CH 3 C(O)-Ser Ser Arg Phe Orn Trp Orn Phe Glu Ser Ser-NH 2 *Orn means L-ornithine
  • SEQ ID NOS: 18 to 21 which have the sequence listings set forth below in Table 4.
  • Table 4 SEQ ID NO: Sequence Listing 18 19 20 CH 3 C(O)-Glu Gln Glu Phe Glu Trp Glu Phe Glu Gln Glu-NH 2 21 CH 3 C(O)-Gln Gln Orn Phe Orn Trp Orn Phe Orn Gln Gln-NH 2
  • Table 5 SEQ ID NO: Sequence Listing 22 CH 3 C(O)-Gln Arg Phe Gln Trp Gln Phe Glu Gln-NH 2 23 CH 3 C(O)-Arg Phe Gln Trp Gln Phe Glu-NH 2 24 CH 3 C(O)-Phe Gln Trp Gln Phe-NH 2 25 CH 3 C(O)-Phe Arg Trp Glu Phe-NH 2 26 CH 3 C(O)-Gln Trp Gln-NH 2 27 CH 3 C(O)-Arg Trp Glu-NH 2
  • each self-assembling peptide comprising a self-assembled peptide polymer useful in the present invention independently is of any of one of SEQ ID NOS: 1 to 27, still more preferably of any of one of SEQ ID NOS: 5, 10, and 11.
  • SEQ ID NOS: 28 to 39 have the sequence listings of SEQ ID NOS: 28 to 39 set forth below in Table 6. Table 6.
  • SEQ ID NO: Sequence Listing 28 29 30 31 32 Lys Gly Ala Arg Arg Gly Ala Lys Arg Gly Gly Lys Lys Leu Ala Arg Lys Ala Leu Lys 33 Lys Gly Ala Arg Arg Leu Ala Lys Arg Ser Gly Lys Lys Val Ala Arg Lys Ala Gly Arg 34 Lys Phe Ala Arg Arg Leu Ala Lys Arg Leu Gly Lys Lys Val Ala Arg Lys Leu Gly Arg 35 Lys Phe Leu Arg Arg Leu Ile Lys Arg Leu Val Lys Lys Val Leu Arg Lys Leu Gly Arg 36 Lys Ala Ala Lys Lys Ala Ala Lys Arg Ala Ala Lys Lys Ala Thr Arg 37 Lys Ala Leu Ly
  • Self-assembling peptides of SEQ ID NOS: 1 to 39 lack supplemental segments, i.e., consist essentially of self-assembling segments.
  • a peptide coating comprises one or more self-assembled peptide polymers.
  • a "self-assembled peptide polymer” means at least two self-assembling peptides are complementarily-bonded, preferably reversibly, to each other.
  • a self-assembled peptide polymer is characterized as having a first portion that comprises part or all of the self-assembling segments of the self-assembling peptides comprising the self-assembled peptide polymer. The self-assembling segments are complementarily-bonded, preferably reversibly, to each other.
  • the self-assembling peptide polymer is further characterized as having a second portion that comprises the supplemental segment(s), which may or may not be complementarily-bonded, preferably reversibly, to each other.
  • a preferred self-assembled peptide polymer comprises a ⁇ -sheet tape.
  • a self-assembled peptide polymer comprises one or more ⁇ -sheet tapes, preferably at least one, more preferably each, ⁇ -sheet tape comprises an anti-parallel arrangement of two or more self-assembling peptides in the self-assembled peptide polymer.
  • a self-assembled peptide polymer comprising two or more ⁇ -sheet tapes, a ribbon comprising two or more stacked ⁇ -sheet tapes, a fibril comprising two or more said ribbons stacked together, or a peptide fiber comprising an entwined plurality of said fibrils. Examples of said ribbon, fibril, and peptide fiber are described in USPAPN 2006/0154852, supra.
  • Figs. 6A to 6D depict a self-assembled peptide polymer 10 comprised of two self-assembling peptides I and 12 and four non-covalent functional group interactions 13, wherein self-assembling peptides 11 and 12 each consist essentially of a self-assembling segment (not separately indicated).
  • Fig. 6B depicts a self-assembled peptide polymer 20 comprised of two self-assembling peptides 21 and 22 and four functional group interactions 23, wherein self-assembling peptide 21 comprises a self-assembling segment 24 and a supplemental segment 25 and self-assembling segment 22 consists essentially of a self-assembling segment (not separately indicated).
  • Fig. 6C depicts a self-assembled peptide polymer 30 comprised of two self-assembling peptides 31 and 32 and four functional group interactions 33, wherein self-assembling peptide 31 comprises a self-assembling segment 34, a supplemental segment 35, and a supplemental segment 36 and self-assembling segment 32 consists essentially of a self-assembling segment (not separately indicated).
  • self-assembling peptide 31 comprises a self-assembling segment 34, a supplemental segment 35, and a supplemental segment 36 and self-assembling segment 32 consists essentially of a self-assembling segment (not separately indicated).
  • 6D depicts a self-assembled peptide polymer 40 comprised of two self-assembling peptides 41 and 42 and four functional group interactions 43, wherein self-assembling peptide 41 comprises a self-assembling segment 44 and a supplemental segment 45 and self-assembling segment 42 comprises a self-assembling segment 46 and a supplemental segment 47 (depicted here in a quasi head-to-tail arrangement, although a quasi head-to-head arrangement is also contemplated).
  • a self-assembled peptide polymer comprising peptide-coated fiber is characterized as having a third portion that is in operative coating contact with a coating-receptive fiber.
  • the third portion typically comprises part or all of the self-assembling segments of the self-assembling peptides comprising the self-assembled peptide polymer.
  • the self-assembled peptide polymer is further characterized as having a fourth portion that optionally is or is not in operative coating contact with the coating-receptive fiber.
  • operative means effective, i.e., via direct or indirect means.
  • operative coating contact means a peptide coating comprising one or more self-assembled peptide polymers is in direct physical contact (i.e., in single layer coatings and the first layer of a multi-layer coating) or indirect physical contact (i.e., sequentially second and higher layers of multi-layer coatings) with a coating-receptive fiber and said one or more self-assembled peptide polymers are physically at least partially wrapped around (as described below) the coating-receptive fiber, interact with functional groups of the coating-receptive fiber as described below, or, preferably, a combination thereof.
  • a partially wrapped coating means at least one complete turn of a self-assembled peptide polymer around the coating-receptive fiber as determined by processing a SEM image thereof with, for example, a QWin image analysis system, supra ).
  • the coating-receptive fiber is coated along substantially (i.e., greater than 80% of) its length. In other embodiments, the coating-receptive fiber is coated along less than 80% of its length.
  • Said operative coating contact preferably comprises a plurality of functional group interactions between functional groups comprising the coating-receptive fiber and functional groups comprising the self-assembled peptide polymers.
  • Such functional group interactions preferably comprise non-covalent interactions, one or more covalent bonds, preferably 2 or fewer covalent bonds, more preferably 1 or 0 covalent bonds, still more preferably 0 covalent bonds, or a combination thereof per self-assembled peptide polymer.
  • non-covalent interactions are electrostatic interactions (ion-ion, ion-dipole or dipole-dipole) or coordinative bonding (metal-ligand); hydrogen bonding; ⁇ - ⁇ stacking interactions; van der Waals forces; and combinations thereof.
  • said covalent bond is a disulfide bond, i.e., the bond of the -sulfur-sulfur- diradical (-S-S-), carbon-oxygen carboxylic ester bond (>C'-C(O)-O-), carbon-oxygen carbonate bond (-O-C(O)-O-), carbon-nitrogen carboxanide bond (>C'-C(O)-N ⁇ ), carbon-nitrogen urea bond (>N-C(O)-N ⁇ ), and carbon-nitrogen or carbon-oxygen carbamate bond (-O-C(O)-N ⁇ ), wherein ">" and " ⁇ " indicate two radical bonds. Still more preferably, said operative coating contact comprises a combination of said at least partially wrapped coating and said plurality of functional group interactions.
  • Reversibility of the "reversible operative coating contact” refers to an ability of a coating-receptive fiber and one or more self-assembled peptide polymers, or an outer layer of a peptide-coated fiber and one or more other self-assembled peptide polymers to form, break, or a combination thereof said operative coating contact.
  • said operative coating contact comprises at least one covalent bond
  • said reversibility may or may not comprise forming, breaking, or a combination thereof, one or more of said covalent bonds.
  • at least one covalent bond is not broken.
  • processes of forming (i.e., coating) and breaking (i.e., releasing a coating) said non-covalent interactions are responsive to coating triggers.
  • a "coating trigger” means a chemical or physical means of inducing assembly of two or more self-assembling peptides into a self-assembled peptide polymer, inducing coating of a coating-receptive fiber by a self-assembled peptide polymer, inducing further coating of a peptide-coated fiber by a same or different self-assembled peptide polymer, or a combination thereof.
  • a total of 0, 1, 2 or more coating triggers are employed.
  • Preferably 0, 1, or 2 coating triggers are employed.
  • a first coating trigger induces assembly of two or more self-assembling peptides into a self-assembled peptide polymer
  • a second coating trigger induces coating of a coating-receptive fiber by the self-assembled peptide polymer, or both.
  • coating triggers induce release of a peptide coating from a peptide-coated fiber.
  • Coating triggers independently are the same or different; when the same, coating triggers preferably are complimentary acting as described later. Preferably, coating triggers are used whenever convenient.
  • Coating triggers useful in the present invention are described in the following publications: US 2002/0132974 ; US 2004/0235048 ; US 2006/0154852 ; Aggeli A., et al., Hierarclaical self-assembly of chiral rod-like molecules as a model for peptide ⁇ -sheet tapes, ribbons, fibrils, and fibers, Proceedings of the National Academy of Sciences (PNAS), October 9, 2001; 98:11857-11862 ; Aggeli A., et al., pH as a Trigger of Peptide ⁇ -Sheet Self-Assembly and Reversible Switching betzveen Nematic and Isotropic Phases, Journal of the American Chemical Society (J. Am.
  • a coating trigger comprises: varying the amino acid residue composition of the self-assembling peptide (i.e., using a different self-assembling peptide); chemically modifying a functional group of an amino acid residue comprising the self-assembling peptide; varying concentration (e.g., by evaporation of peptide-coating solvent) of the self-assembling peptide dissolved in a medium (e.g., water, an aqueous NaCl solution, an organic peptide-coating solvent such as chloroform or methanol, or a combination of water and a water miscible organic peptide-coating solvent); varying pH of a medium; varying ionic strength of a medium by adding ions (e.g., by using a 130 mM or 145 mM solution of NaCl in water instead of water as the medium), wherein the ions are anions or cations and are chosen from a Hofmeister series; adding one or more peptide-coating solvents (e.g.,
  • An additional coating trigger comprises radiation (e.g., light).
  • Another coating trigger comprises effectively mixing the one complementary self-assembling peptide with the other, as described by Aggeli A., et al., Self-Assembling Peptide Polyelectrolyte ⁇ -Sheet Complexes Form Nematic Hydrogels, Angewandte Chemie Int. Ed., 2003; 43: 5603-5606 ,
  • a coating trigger more preferably each coating trigger where there are two or more coating triggers, still more preferably each coating trigger for triggering release of a self-assembled peptide polymer from a peptide-coated fiber is environmentally activated (as opposed to being activated by a consciously-performed man-made activity).
  • Such coating triggers respond to one or more natural changes in an environment that is in operative communication with a free self-assembling peptide or, preferably, a peptide coating comprised of a self-assembled peptide polymer.
  • two coating triggers are the same, preferably they are complimentarily acting (i.e., have essentially opposite coating effects on self-assembled peptide polymers).
  • complimentarily acting pH coating triggers are lowering pH of a medium (e.g., from pH 8.0 to pH 6.0) to trigger release of a self-assembled peptide polymer coating from a peptide-coated fiber that is in contact with the medium and raising said pH (e.g., from pH 6.0 to pH 8.0) to stop release of the self-assembling peptide polymer coating or trigger coating of a fiber (e.g., a coating-receptive fiber or peptide-coated fiber) in contact with the medium with a self-assembled peptide polymer, or vice versa.
  • a medium e.g., from pH 8.0 to pH 6.0
  • pH e.g., from pH 6.0 to pH 8.0
  • complimentarily acting and environmentally activated coating triggers is a peptide-coated fiber of the present invention comprising an antimicrobial self-assembling peptide, wherein the peptide-coated fiber is in therapeutic contact with a wound infected with a bacteria in a patient having the wound.
  • Such a bacteria may naturally create in the wound a micro-environment comprising a fluid (e.g., biological fluid) having pH less than 7.0, and thereby trigger release (e.g., dissolution) of self-assembled peptide polymer from the peptide-coated fiber (e.g., peptide coating releases from a coating-receptive fiber or a top layer or more of a multilayer peptide coating releases therefrom) and disassembly of the self-assembled peptide polymer into the antimicrobial self-assembling peptide.
  • a fluid e.g., biological fluid having pH less than 7.0
  • the pH of the micro-environment comprising the fluid will naturally return to the patient's physiological pH 7.4, and so trigger a complimentary re-coating of the fiber.
  • re-coating comprises assembly of the released antimicrobial self-assembling peptide into a self-assembled peptide polymer, which then coats the fiber.
  • the second coating trigger stops further dissolution of outer layers of the coating, causes recoating, or both.
  • Peptide-coated fibers of the present invention may be prepared by any one of a number of processes.
  • the peptide-coated fibers are prepared by first fabricating a coating-receptive fiber useful in the present invention, and then contacting a self-assembled peptide polymer to the coating-receptive fiber, wherein the coating-receptive fiber optionally is or is not further processed (e.g., cleaned and collected) before it is contacted to the self-assembled peptide polymer.
  • the coating-receptive fiber is fabricated and essentially simultaneously contacted to the self-assembled peptide polymer.
  • the coating-receptive fiber of the peptide-coated fiber comprises a MSA material, more preferably a MSA material that is a poly(ester-amide), poly(ether-amide), poly(ester-urea), poly(ether-urea), poly(ester-urethane), or poly(ether-urethane), or a mixture thereof.
  • Articles comprising a peptide-coated fiber are manufactured from said peptide-coated fiber.
  • the articles further comprise the aforementioned collector employed for fabricating the coating-receptive fiber.
  • said articles are manufactured from a coating-receptive fiber to give intermediate non-(peptide-coated) articles, and said non-(peptide-coated) articles are coated with at least one self-assembled peptide polymer according to a process of the third embodiment of the present invention.
  • Said invention process is beneficially effective for coating exterior fibers (i.e., fibers that are proximal to surfaces of said non-(peptide-coated) articles) fibers and, optionally, interior fibers (i.e., fibers that are distal from surfaces of said non-(peptide-coated) articles), wherein "surfaces" means exterior and interior surfaces.
  • said invention process maintains a contacting step for a time sufficient to allow a medium to penetrate (e.g., by injection or percolation) from a surface and contact said interior fibers.
  • any particular fiber has a portion that is at the exterior of, and a portion that is interior in, a non-(peptide-coated) article.
  • an article of the second embodiment of the present invention is useful in a medical, personal hygiene, cleaning, or filtration application.
  • a bandage e.g., for treating wounds
  • a therapeutic patch i.e., a patch useful for transdermally delivering a therapeutic agent to a patient
  • a medical garment e.g., surgical gown and mask
  • a medical fabric e.g., a sheet for covering a bed in a patient or operating room, a curtain for screening off a patient treatment area, a wall covering for walls in a patient or operating room, a surgical drape, and a surgical towel).
  • Examples of invention articles for preferred personal hygiene applications are diaper stock; feminine hygiene stock; a stocking (e.g., a sock); linings (e.g., for shoes and gloves); and underwear stock.
  • Examples of invention articles for preferred cleaning applications are wipes (e.g., baby wipes); cleaning cloths; and food preparation surface barriers. More preferred are invention articles for anti-infective cleaning applications.
  • Examples of invention articles for preferred filtration applications are filter stock, including filter stock for air filtration and liquid filtration applications.
  • an article of the second embodiment of the present invention is maintained (e.g., stored) in a dry condition until ready for use.
  • an anti-infective cleaning cloth is kept in a dry condition until it is needed for use in an anti-infective cleaning application, whereupon it is activated by contact with a liquid such as water, sterile saline, or a biological fluid (e.g., blood from raw meat).
  • a liquid such as water, sterile saline, or a biological fluid (e.g., blood from raw meat).
  • Conventional anti-infective cleaning cloths typically are stored in a moist environment, which promotes loss of anti-infective potency of such cloths.
  • Anti-infective cleaning cloths and other invention articles e.g., bandages and stock for personal hygiene applications
  • useful in anti-infective applications are expected to possess longer shelf-lives compared to conventional moistened articles.
  • anti-infective means antiviral, antifungal, antiparasitic, antialgae, and, preferably, antimicrobial (i.e., antibacterial).
  • antimicrobial i.e., antibacterial
  • Assays for testing anti-infective properties of peptides are known. Examples of such assays are found, for example, in United States Patent Number 6,85856 .
  • Various methods including, for example, carbon-13 nuclear magnetic resonance ( 13 C-NMR) and, preferably, proton nuclear magnetic resonance ( 1 H-NMR) may be used to determine monomer purity, copolymer composition, and copolymer number average molekular weight utilizing the CH 2 OH end groups.
  • 13 C-NMR carbon-13 nuclear magnetic resonance
  • 1 H-NMR proton nuclear magnetic resonance
  • peak assignments are dependent on the specific structure being analyzed as well as the NMR solvent, concentration, and temperatures utilized for measurement.
  • d4-acetic acid is a convenient NMR solvent and is the solvent used unless otherwise noted.
  • ester amide monomers of the type called DD that are methyl esters
  • a preferred amide diol is the condensation product prepared from ethylene diamine and ⁇ -caprolactone, coded C2C in the preparations below, and which has the following structure: HO-(CH 2 ) 5 -CONH-(CH 2 ) 2 -NHCO-(CH 2 ) 5 -OH.
  • a preferred diamide diacid functionality that is the condensation product prepared from ethylene diamine and dimethyl adipate is coded A2A in the preparations below.
  • Another preferred diamide diacid functionality that is the condensation product prepared from butylene diamine and dimethyl adipate is coded A4A in the preparations below.
  • Step (a) Preparation of the diamide diol ethylene-N,N'-dihydroxyhexanamide (C2C).
  • C2C monomer is prepared by reacting 1.2 kilograms (kg) of ethylene diamine (EDA) with 4.56 kg of ⁇ -caprolactone under a nitrogen blanket in a stainless steel reactor equipped with an agitator and a cooling water jacket. An exothermic condensation reaction between the ⁇ -caprolactone and the EDA occurs which causes the temperature to rise gradually to 80°C. A white deposit forms and the reactor contents solidify, at which the stirring is stopped. The reactor contents are then heated to 160°C at which temperature the solidified reactor contents melt. The liquid product is then discharged from the reactor into a collecting tray. A nuclear magnetic resonance study of the resulting product shows that the mole concentration of C2C in the product exceeds 80 percent. The melting point of the C2C diamide diol product is 140°C. Step (b1) Contacting C2C with dimethyl adipate.
  • EDA ethylene diamine
  • a devolitizer reactor is charged with 2.622 kg liquid dimethyl adipate and 2.163 kg of the solid C2C diamide diol produced as described above.
  • the reactor contents are brought slowly under nitrogen purge to a temperature of 140°C in order to melt the C2C in the reaction mixture.
  • Step (b2) Contacting the composition with 1,4-butanediol without further addition of non-volatile diols, acids or branching agents.
  • step (b) 1.352 kg of 1,4-butandiol are added to the reactor contents of step (b) followed by 105 milliliters (mL) of a 10 percent by weight solution of tetrabutoxy titanium (IV) in 1,4-butanediol.
  • the resulting reaction results in the formation of methanol which is then removed as vapor by the nitrogen purge from the reactor system.
  • the pressure in the system is maintained at atmospheric pressure, and temperature is gradually raised to 180°C.
  • the reaction and distillation of methanol is continued until the evolution of methanol subsides.
  • the pressure in the reactor is then lowered to an absolute pressure of 450 millibars (mbar) and then stepwise to 20 mbar, resulting in further evolution of methanol vapor from the reaction mixture.
  • the resulting polymer designated_PEA P2-8 C2C-50% (i.e., 50 mole % C2C), has a M n (by 1 H-NMR in d 4 -acetic acid) of 7480 g/mol, i.e., about 7500 g/mol.
  • MSA Polymer Preparation 2 preparation of polymer from C2C, Dimethyl Adipate, and 1,4-Butanediol (a PEA-C2C50%)
  • Ti(OBu) 4 catalyst is injected from Feed cylinder 2 as 34.84 gram of a 10% by weight solution in 1,4-BD (4000 ppm calculated on DMA; 3.484 g catalyst plus 31.36 g 1,4-BD: total content of 1,4-BD is 0.450 kg).
  • the kneader temperature is increased stepwise to 180 °C over a period of 2 hours to 3 hours at atmospheric pressure; initially with low (to prevent entrainment of the monomers DMA and BD) nitrogen sweep applied.
  • Methanol fraction is distilled off and collected (theoretical amount: 0.320 kg) in a cooling trap.
  • the kneader pressure is stepwise decreased first to 50 mbar-20 mbar and further to 5 mbar to complete the methanol removal and to initiate the 1,4-BD distillation.
  • the pressure is further decreased ⁇ 1 mbar or as low as possible, until the slow but steady distillation of 1,4 butane diol is observed (calculated amount 0.225 kg).
  • the temperature is raised to 190 °C to 200 °C at maximum as to avoid discoloration.
  • Towards the end of the reaction samples are taken from the reactor to check the viscosity.
  • the target point is 2 Pa.s. at 180 °C for a molecular weight M n (by 1 H-NMR) of 5,000 g/mol.
  • the kneader is cooled to about 150 °C (depending on torque measured) and brought to atmospheric pressure under nitrogen blanket and the_PEA-C2C50% polymer is collected as AMD PBA 18-05. From the polymer 2 mm thick compression molded plaques were produced. Prior to compression molding, the polymer was dried at 65 °C under vacuum for about 24 hours. Plaques of 160 mm x 160 mm x 2 mm were obtained by compression molding isothermally at 150 °C, 6 minutes at 10 bar and afterwards 3 minutes at 150 bar. The samples were cooled from 150 °C to room temperature at 20 °C/minute.
  • the A2A is prepared as in Preparation 3. Under an inert atmosphere into a 250 mL round bottom flask is loaded titanium (IV) butoxide (0.107 grams, 0.315 mmol), A2A (36.21 grams, 10.51 mmol), dimethyl adipate (18.31 grams, 0.1051 mol), and 1.4-butanediol (37.9 grams, 0.4205 mol). Polymerization reaction is run with overhead stirring, nitrogen/vacuum, heating, and use of a distillation head.
  • Reaction profile is as follows: 2.0 hrs from 160 °C to/at 175 °C, nitrogen gas; 45 minutes, 450 Torr to 10 Torr, 175 °C; 1.5 hours, about 10 Torr, 175 °C, 2 hours 0.46 Torr to 0.38 Torr, 175 °C: 2 hours 0.47 Torr, 190 °C; and 2 hours 0.7 Torr to 0.42 Torr, 210 °C.
  • Coating-Receptive Fiber Preparation 1 Solution-based electrospinning of PEA P2-8 C2C-50
  • This example demonstrates the ability to electrospin submicron fibers from a solution of PEA P2-8 C2C-50 of MSA Polymer Preparation 1, with number average molecular weight of about 7500 g/mol, in chloroform.
  • the voltage is 18 kV and is applied 50% positive at the needle and 50% negative at the conductor.
  • the syringe is a 10 mL syringe with an inner diameter of 15 mm. This diameter is used to calibrate the syringe pump.
  • the needle is 20 gauge x 2" needle (0.584 mm inner diameter x 5.1 cm length). Distance from the syringe nozzle to the collector is 20 centimeters (cm).
  • the syringe pump flow rate of the solution is 20 mL/hour.
  • This example further demonstrates the ability to electrospin submicron fibers from concentrated solutions PEA P2-8 C2C-50 of MSA Polymer Preparation 1 with number average molecular weight of about 7500 g/mol.
  • the experiments cover concentrations from 6 wt% to 18 wt% in chloroform. Representative samples of the results are shown in Table 9.
  • the voltage, reported in kilovolts (kV) provided in Table 9 below is applied 50% positive at the needle and 50% negative at the conductor.
  • the syringe is a 10 mL syringe with an inner diameter of 15 mm. This diameter is used to calibrate the syringe pump.
  • the needles are 20 gauge x 2" needle (0.584 mm inner diameter x 5.1 cm length), 22 gauge x 2" needle (0.394 mm inner diameter x 5.1 cm length), and 24 gauge x 1.0" (0.292 mm inner diameter x 2.5 cm length).
  • Distance from the syringe nozzle to the collector is presented in centimeters (cm).
  • the syringe pump flow rate ranges from 2.5 mL/hour to 10 mL/hour. Collection times ranged from 45 seconds to 5 minutes.
  • Mean fiber diameter, median fiber diameter, mode fiber diameter and standard deviation of fiber diameter are given in micrometers ( ⁇ m). Table 9. Sample No.
  • the 6 wt% solutions produced a result with average fiber diameters of 61 nm.
  • the 11 wt% solutions produced a result with average fiber diameters of 239 nm.
  • the 18 wt% solutions produced a result with a median fiber diameter of 830 nm.
  • PEA AMD 18-05 C2C-50% (granulated crude reactor MSA material) from MSA Polymer Preparation 2 was processed on electrospinning equipment directly from the melt without any additives.
  • the spin electrode consisting of a needle syringe filled with melt, is heated with two heating elements proportional-integral-derivative (PID) controlled, having a temperature range up to 300 °C. Needle syringe temperature greater than (>)135 °C. Applied voltage 30 kV Environmental temperature is 20 °C to 150 °C by hot air. Electrode gap is 3 cm -19 cm.
  • the fibrous MSA material was collected on collector fabric. Result: nanofibers of about 200 nm-4000 nm diameters were produced as determined by SEM.
  • Coating-receptive fiber Preparation 4 melt blowing of PEA P2-8 C2C-50 of MSA Polymer Preparation 1
  • a melt blowing device comprising a die block having a portion that functions as a die tip, the die tip defining a plurality of apertures and having an aperture density of 55 apertures per square inch, i.e., 8.5 apertures per square centimeter, and an aperture dimension of 0.3 millimeter diameter and a length-to-diameter ratio of 10.
  • the die block further comprises a 100-mesh screen, which is used to filter material to be melt blown before the material enters the apertures.
  • the PEA P2-8 C2C-50 of MSA Polymer Preparation 1 is heated to 170 °C and stretch gas comprising air at 170 °C is employed. Fibers are collected in a moving collector comprising a web belt.
  • Acceptable combinations of process line speed and releasing of fibers from the web belt are determined by trial and error until production of non-woven mats comprising the PEA P2-8 C2C-50 are obtained at fiber densities of 10 grams per square meter (gsm), 25 gsm, and 50 gsm.
  • Sizes of the resulting melt blown fibers are determined by SEM microscopy. Sample pieces of the melt blown fibers are cut out with scissors and glued to aluminum SEM stubs with carbon paint. The pieces are coated with 5 nm thick layer of osmium tetroxide using a Filgen Osmium Plasma Coater OPC-60A. The pieces are imaged in an FEI Nova NANOSEM ® field emission gun scanning electron microscope (serial number D8134, General Nanotechnology LLC) at 5 kiloelectronvolts (keV), spot size 3 mm, and a working distance of 5 mm. Depending on the size of the fibers, from 5 to 20 images are collected at various magnifications.
  • Relative frequency (RF) of average fiber diameter (AFD) is RF: 5% (AFD ⁇ 500 nm); 42% (AFD from 500 nm to 1000 nm): 32% (AFD from 1000 nm to 2000 nm); 15% (AFD from 2000 nm to 3000 nm); 3% (AFD from 3000 nm to 5000 nm); and 2% (AFD >5000 nm) (RF does not add to 100% due to rounding).
  • NOVASYNTM Novabiochem AG, Switzerland
  • tetra gel rink amide (Novasyn TGR) resin is soaked in N,N-dimethylformamide (DMF) for approximately three hours.
  • the resin mixture is transferred to a reaction vessel comprising a column having a sintered frit base, which allows an agitating gas to bubble up from below and liquids from above to be drained away.
  • the resin is activated with 20% piperidine/DMF volume/volume (v/v) for 1 minute while bubbling with nitrogen (5 milliliters (mL) per 0.5 g resin). Then it is washed five times with DMF.
  • a solution of four mole equivalents of N-(9-fluorenylmethylformoyl)-amino acid (Fmoc-AA-OH) and four mole equivalents of O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) is dissolved in 1.6 mL of 10 % diisopropylethylamine in DMF (v/v), then diluted to 20 mL with additional DMF. This solution is added to the resin and the resulting mixture is left to couple for 2.5 hours, and then washed four times with DMF.
  • each of the unacetylated peptides of step (a) are acetylated at the N-terminal and then cleaved from the resin.
  • To separate DMF solutions of each of the resin-bound unacetylated peptides of step (a) are added 3x8.5 mL of a solution of 0.7 mL acetic anhydride and 25 mL of DMF and a solution of 0.06 mL of pyridine and 25 mL DMF.
  • the resulting reaction solution is allowed to drain off through the sintered frit under gravity for approximately 30 minutes, leaving resin-bound acetylated peptide behind.
  • the resin is washed twice with DMF, and dried under a vacuum.
  • the resulting dried resin is washed with DMF, then 2 times with dichloromethane. When the resin floats in the dichloromethane, it is washed with methanol until it sinks, and the resulting resin is transferred to a beaker where it is covered and dried under vacuum overnight.
  • a cleavage mixture comprising phenol (0.1 g), anisole (0.2 mL), ethanedithiol (0.4 mL), water (0.2 mL), and trit-luoroacetic acid (TFA) (9.2 mL) is added to the dried resin, and the mixture is agitated for 3 hours.
  • the resulting solution above the resin is filtered off into a round bottom flask, and the resin is washed 2 times with 5 mL of TFA, and then dried under vacuum.
  • the solution filtrate which contains self-assembling peptide of any one of SEQ ID NOS: 22 to 27 that has been cleaved from the resin, is concentrated to 1 mL to 2 mL of an oil on a rotary evaporator.
  • a portion of the oil (1 mL) is added dropwise to cold diethyl ether (approximately 30 mL), and after precipitation occurs the resulting suspension is centrifuged for 10 minutes. The excess diethyl ether is decanted. Fresh cold diethyl ether (30 mL) is added and an additional 1 mL portion of the oil is added dropwise, and this step is repeated until all of the oil is treated. The resulting peptide residue is left to dry over night, then dissolved in distilled water and freeze dried to give the self-assembling peptide of any one of SEQ ID NOS: 22 to 27.
  • Example 1 peptide-coated fiber comprising a coating-receptive fiber of Coating-Receptive Fiber
  • Preparation 1 comprised of a poly(ester-amide) PEA P2-8 C2C-50% and a self-assembling peptide of SEQ ID NO: 11
  • a control sample of non-woven fabric comprised of one or more coating-receptive fibers of Coating-Receptive Fiber Preparation 1 is set aside.
  • Three test samples of non-woven fabric comprised of one or more coating-receptive fibers of Coating-Receptive Fiber Preparation 1 are placed in three separate 10 milligram per milliliter (mg/mL) monomeric peptide solutions of the self-assembling peptide of SEQ ID NO: 11 in water (with now added salt) at pH 8 and room temperature, and the peptide solution is allowed 1 hour to absorb within the PEA non-woven fabric.
  • microliters of concentrated HCl solution (more than 0.1M HCl in water) are added to lower the pH of the solutions to pH 6, pH 4, and pH 2, respectively, in order to trigger self assembly of the monomeric peptides into self-assembled peptide polymers comprised of ⁇ -sheets and coating of the coating-receptive fiber(s) with the self-assembled peptide polymers.
  • the test samples are left overnight in the resulting solutions/gels, and then removed and allowed to dry.
  • Fig. 3A is a SEM image (60,000 times magnification) of uncoated PEA fiber that is provided for comparison.
  • Fig. 3B is a SEM image (50,000 times magnification) of peptide-coated PEA fiber wherein the peptide coating is prepared as described above in Example 1 by switching the pH of the monomeric peptide solution from pH 8 to pH 6.
  • the self-assembling peptide used for the coating is of SEQ ID NO: 11, as in Example 1 above.
  • Fig. 4A is a SEM image (60,000 times magnification) of uncoated PEA fiber that is provided for comparison.
  • Fig4B is a SEM image (60,000 times magnification) of peptide-coated PEA fiber wherein the peptide coating is prepared as described above in Example 1 by switching the pH of the monomeric peptide solution from pH 8 to pH 4. After preparation, the peptide-coated PEA fiber is immersed in pure (i.e., distilled) water, left for 17.5 hours, to test for dilution rate of the peptide coating when in contact with pure water, then dried. It can be seen from Fig. 4B that most, if not all, of the peptide coating dissolves away, as no peptide coating is seen by SEM.
  • the self-assembling peptide used for the coating is of SEQ ID NO: 11, as in Example 1 above.
  • Figs. 5A and 5B are SEM images (at respective magnifications 15,000 times and 90,000 times) of peptide-coated PEA fiber, which is prepared as described above in Example 1 by switching the pH of the monomeric peptide solution from pH 8 to pH 4. After preparation, the peptide coated PEA is immersed in physiological-like solution (130 millimolar (mM) NaCl in water, pHabout7.4), left for 1 week, to test for dilution rate of the peptide coating when in contact with physiological-like solution, and then dried. The resulting dried peptide-coated PEA fiber is placed in contact with physiological-like solutions to test for dilution rate of the peptide coating thereinto. It can be seen from Fig.
  • physiological-like solution 130 millimolar (mM) NaCl in water, pHabout7.4
  • Fig. 5A that the peptide coating is still visible on the PEA fibers, and thus Fig. 5A seems to show that no significant dissolution of the peptide coating takes place under these conditions.
  • Fig 5B again the peptide coating is still visible on the PEA fibers, but some areas of the PEA fibers seem to have no or very thin peptide coating (see the bottom right-hand corner of the SEM image of Fig. 5B ).
  • the self-assembling peptide used for the coating is of SEQ ID NO: 11, as in Example 1 above.
  • Example 1 demonstrate that a coating-receptive fiber comprising a MSA material useful in the present invention is coated with a self-assembling peptide useful in the present invention to provide a peptide-coated fiber of the first embodiment of the present invention, the peptide coating being in reversible operative coating contact with the coating-receptive fiber.

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  • Engineering & Computer Science (AREA)
  • Textile Engineering (AREA)
  • Treatments For Attaching Organic Compounds To Fibrous Goods (AREA)
  • Spinning Methods And Devices For Manufacturing Artificial Fibers (AREA)

Claims (15)

  1. Fibre enrobée d'un peptide comprenant une fibre réceptrice d'enrobage et un enrobage peptidique, l'enrobage peptidique étant en contact d'enrobage opérationnel réversible avec la fibre réceptrice d'enrobage ; dans laquelle la fibre réceptrice d'enrobage a un diamètre de 10 micromètres (µm) ou moins, et comprend un matériau d'auto-assemblage moléculaire choisi parmi un poly(ester-amide), un poly(éther-amide), un poly(ester-urée), un poly(éther-urée), un poly(ester-uréthane) et un poly(éther-uréthane), ou un mélange de ceux-ci, et l'enrobage peptidique comprend au moins un polymère peptidique auto-assemblé, dans laquelle chaque polymère peptidique auto-assemblé comprend deux ou plusieurs peptides d'auto-assemblage et chaque peptide d'auto-assemblage est le même ou différent et comprend indépendamment un segment d'auto-assemblage de 2 à 59 résidus d'acides aminés.
  2. Fibre enrobée d'un peptide selon la revendication 1, dans laquelle le poids moléculaire moyen en nombre (Mn) du matériau d'auto-assemblage moléculaire est compris entre environ 1 000 grammes par mole (g/mol) et environ 50 000 g/mol, inclus.
  3. Fibre enrobée d'un peptide selon la revendication 1 ou 2, dans laquelle le matériau d'auto-assemblage moléculaire comprend des unités d'auto-assemblage comprenant de multiples réseaux de liaisons hydrogènes et en option dans laquelle les multiples réseaux de liaisons hydrogènes ont une constante d'association K(assoc) supérieure à 103 M-1.
  4. Fibre enrobée d'un peptide selon la revendication 3, dans laquelle les multiples réseaux de liaisons H comprennent au moins 4 ou une moyenne de 2 à 8 sites de liaison hydrogène donneur-accepteur par unité d'auto-assemblage.
  5. Fibre enrobée d'un peptide selon l'une quelconque des revendications précédentes, dans laquelle la fibre réceptrice d'enrobage a un diamètre moyen inférieur à environ 1 000 nanomètres (nm).
  6. Fibre enrobée d'un peptide selon l'une quelconque des revendications précédentes, dans laquelle le matériau d'auto-assemblage moléculaire est caractérisé par l'un ou les deux de (A) et (B) :
    (A) (i) une viscosité à l'état fondu inférieure à 100 pascals-seconde (Pa.s) entre Tm et environ 40 degrés Celsius (°C) au-dessus de Tm ou (ii) une viscosité à l'état fondu dans la plage de 1 Pa.s à 50 Pa.s. à 160 °C ou (iii) une viscosité à l'état fondu dans la plage de 0,1 Pa.s. à 30 Pa.s. dans la plage de températures comprise entre 180 °C et 220 °C ou (iv) une viscosité à l'état fondu ayant une viscosité newtonienne sur la plage de fréquence de 10-1 à 10-2 radians par seconde à une température comprise entre Tm et environ 40 °C au-dessus de Tm ;
    (B) l'une quelconque ou plusieurs des caractéristiques suivantes (i) un module d'élasticité compris entre environ 4 mégapascals (MPa) et environ 500 MPa à 20 °C (ii) au moins un point de fusion Tm supérieur à 25 °C et (iii) une température de transition vitreuse Tg supérieure à -80 °C.
  7. Fibre enrobée d'un peptide selon l'une quelconque des revendications 1 à 6, dans laquelle le matériau d'auto-assemblage moléculaire comprend des unités de répétition de Formule I :
    Figure imgb0031
     et au moins une seconde unité de répétition choisie parmi les unités d'ester-amide de Formule II et III :
    Figure imgb0032
    Figure imgb0033
     et les unités ester-uréthane de Formule IV :
    Figure imgb0034
     ou des combinaisons de celles-ci dans laquelle :
    R représente à chaque occurrence, indépendamment, un groupement hydrocarbylène non aromatique C2-C20, un groupement hétérohydrocarbylène non aromatique C2-C20 ou un groupement oxyde de polyalkyle ayant un poids moléculaire de groupement compris entre environ 100 grammes par mole et environ 5 000 grammes par mole ;
    R1 à chaque occurrence représente indépendamment une liaison ou un groupement hydrocarbylène non aromatique C1-C20 ;
    R2 à chaque occurrence représente indépendamment un groupement hydrocarbylène non aromatique C1-C20 ;
    RN représente -N(R3)-Ra-N(R3)-, où R3 à chaque occurrence représente indépendamment H ou un alkylène C1-C6 et Ra représente un groupement hydrocarbylène non aromatique C2-C20 ou RN représente un groupement hétérocycloalkyle C2-C20 contenant les deux atomes d'azote, dans laquelle chaque atome d'azote est lié à un groupement carbonyle selon la formule (III) ci-dessus ;
    n est au moins 1 et a une valeur moyenne inférieure à 2 ; et
    w représente la fraction molaire de l'ester de la Formule I, et x, y et z représentent les fractions molaires de l'amide ou de l'uréthane des Formules II, III et IV, respectivement, où w+x+y+z = 1, et 0 < w < 1, et au moins l'un parmi x, y et z est supérieur à zéro mais inférieur à 1.
  8. Fibre enrobée d'un peptide selon l'une quelconque des revendications 1 à 6, dans laquelle le matériau d'auto-assemblage moléculaire est un polymère ou un oligomère de Formule II ou III :
    Figure imgb0035
    Figure imgb0036
     dans laquelle,
    R représente à chaque occurrence, indépendamment, un groupement hydrocarbylène non aromatique C2-C20, un groupement hétérohydrocarbylène non aromatique C2-C20 ou un groupement oxyde de polyalkyle ayant un poids moléculaire de groupement compris entre environ 100 grammes par mole et environ 5 000 grammes par mole ;
    R1 à chaque occurrence représente indépendamment une liaison ou un groupement hydrocarbylène non aromatique C1-C20 ;
    R2 à chaque occurrence représente indépendamment un groupement hydrocarbylène non aromatique C1-C20 ;
    RN représente -N(R3)-Ra-N(R3)-, où R3 à chaque occurrence représente indépendamment H ou un alkylène C1-C6 et Ra représente un groupement hydrocarbylène non aromatique C2-C20 ou RN représente un groupement hétérocycloalkyle C2-C20 contenant les deux atomes d'azote, dans laquelle chaque atome d'azote est lié à un groupement carbonyle selon la formule (III) ci-dessus ;
    n est au moins 1 et a une valeur moyenne inférieure à 2 ; et
    x et y représentent la fraction molaire, dans laquelle x+y = 1, et 0≤x≤1, et 0≤y≤1.
  9. Fibre enrobée d'un peptide selon l'une quelconque des revendications précédentes, dans laquelle ledit au moins un polymère peptidique auto-assemblé comprend une bande de feuille-bêta et en option dans laquelle la bande de feuille-bêta est dans un agencement antiparallèle.
  10. Fibre enrobée d'un peptide selon l'une quelconque des revendications 1 à 8, dans laquelle ledit au moins un polymère peptidique auto-assemblé comprend deux ou plusieurs bandes de feuille β, un ruban constitué de deux ou plusieurs bandes de feuille β empilées, une fibrille constituée de deux ou plusieurs desdits rubans empilés ensemble, ou une fibre peptidique constituée d'une pluralité enlacée desdites fibrilles.
  11. Fibre enrobée d'un peptide selon l'une quelconque des revendications précédentes, dans laquelle chaque segment d'auto-assemblage comprend indépendamment de 4 à 40 résidus d'acides aminés.
  12. Fibre enrobée d'un peptide selon l'une quelconque des revendications précédentes, dans laquelle chaque peptide d'auto-assemblage est indépendamment de l'un quelconque des SEQ ID N° : 1 à 27.
  13. Fibre enrobée d'un peptide selon l'une quelconque des revendications 1 à 11, au moins un peptide d'auto-assemblage comprenant en outre indépendamment un ou deux segments supplémentaires, chaque segment supplémentaire comprenant indépendamment 1 ou plusieurs résidus d'acides aminés et étant un résidu d'une expression protéinique du peptide d'auto-assemblage.
  14. Procédé de fabrication d'une fibre enrobée d'un peptide selon l'une quelconque des revendications 1 à 13, le procédé comprenant les étapes consistant à : (a) mettre en contact une fibre réceptrice d'enrobage qui a un diamètre de 10 µm ou moins et comprend un matériau d'auto-assemblage moléculaire choisi parmi un poly(ester-amide), un poly(éther-amide), un poly(ester-urée), un poly(éther-urée), un poly(ester-uréthane) et un poly(éther-uréthane), ou un mélange de ceux-ci, avec un milieu comprenant au moins un polymère peptidique auto-assemblé et un solvant d'enrobage peptidique, dans laquelle ledit au moins un polymère peptidique auto-assemblé est dissous dans le solvant d'enrobage peptidique et entre en contact avec ladite fibre réceptrice d'enrobage, dans laquelle chaque polymère peptidique auto-assemblé comprend deux ou plusieurs peptides d'auto-assemblage et chaque peptide d'auto-assemblage est le même ou différent et comprend indépendamment un segment d'auto-assemblage de 2 à 59 résidus d'acides aminés ; et (b) laisser l'au moins un polymère peptidique auto-assemblé enrober au moins partiellement la fibre réceptrice d'enrobage ; dans laquelle le procédé produit l'au moins une fibre enrobée de peptide.
  15. Article constitué de la fibre enrobée de peptide selon l'une quelconque des revendications 1 à 13.
EP09791420.4A 2008-08-13 2009-08-12 Fibres enrobées d'un peptide Not-in-force EP2331743B1 (fr)

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