WO2021240271A1 - Encapsulation d'agents antimicrobiens pour pansements perfectionnés - Google Patents

Encapsulation d'agents antimicrobiens pour pansements perfectionnés Download PDF

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Publication number
WO2021240271A1
WO2021240271A1 PCT/IB2021/053808 IB2021053808W WO2021240271A1 WO 2021240271 A1 WO2021240271 A1 WO 2021240271A1 IB 2021053808 W IB2021053808 W IB 2021053808W WO 2021240271 A1 WO2021240271 A1 WO 2021240271A1
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Prior art keywords
wound dressing
growth factor
collagen
dressing composition
wound
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PCT/IB2021/053808
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English (en)
Inventor
Prathamesh Madhav KHARKAR
Kristine M. Kieswetter
Gabriel RIGHES
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Kci Licensing, Inc.
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Publication of WO2021240271A1 publication Critical patent/WO2021240271A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/44—Medicaments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/225—Mixtures of macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • A61L2300/104—Silver, e.g. silver sulfadiazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/202—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with halogen atoms, e.g. triclosan, povidone-iodine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
    • A61L2300/206—Biguanides, e.g. chlorohexidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/21—Acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/30—Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A61L2300/414—Growth factors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/428—Vitamins, e.g. tocopherol, riboflavin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
    • A61L2300/622—Microcapsules

Definitions

  • the present technology relates generally to wound dressing compositions that include a mixture of a collagen, an oxidized regenerated cellulose (ORC), and a microcapsule that includes an agent.
  • Such wound dressing compositions may be used to treat and/or prevent an infection in a wound upon application.
  • dressings are generally known in the art for use in treating an injury or other disruption of tissue. Such wounds may be the result of trauma, surgery, or disease, and may affect skin or other tissues.
  • dressings may control bleeding, absorb wound exudate, ease pain, assist in debriding the wound, protect wound tissue from infection, or otherwise promote healing and protect the wound from further damage. Infections can retard wound healing and, if untreated, can result in tissue loss, systemic infections, septic shock, amputation, and death.
  • bacterial biofilms may also form in a wound presenting further challenges in wound therapy, particularly chronic wounds.
  • wound dressing products that can, upon application to a wound, deliver antimicrobial agents over a period of time in order to prevent or reduce infections in a wound upon application, and over time.
  • a wound dressing composition includes about 30 wt.% to about 95 wt.% of a collagen with a weight-average molecular weight of about 5,000 to about 100,000, about 30 wt.% to about 70 wt.% oxidized regenerated cellulose (ORC) with a weight-average molecular weight of about 50,000 to about 1,000,000, and a microcapsule that includes an agent encapsulated in a polymer.
  • ORC oxidized regenerated cellulose
  • a method for treating a subject in need thereof includes administering to the wound a wound dressing composition of any embodiment disclosed herein.
  • a kit is provided that includes a wound dressing composition of any embodiment disclosed herein as well as instructions for use.
  • FIG. 1 provides a non-limiting image of an embodiment of a microcapsule of the present technology, where the particular amount of agent in the microcapsule was about 47 wt.%.
  • FIG. 2 provides a non-limiting image of an embodiment of a microcapsule of the present technology, synthesized using a co-axial nozzle technique with a 750 pm nozzle and using an alginate based solution, according to the working examples.
  • FIG. 3 provides a non-limiting image of an embodiment of a microcapsule of the present technology, synthesized using a co-axial nozzle technique with a 300 pm nozzle and using an alginate based solution, according to the working examples.
  • FIG. 4 provides a non-limiting image of an embodiment of a microcapsule of the present technology, synthesized using a co-axial nozzle technique with a 200 pm nozzle and using an alginate based solution, according to the working examples.
  • FIG. 5 provides a non-limiting image of an embodiment of a microcapsule of the present technology, synthesized using a co-axial nozzle technique with a 450 pm nozzle and using an alginate based solution, according to the working examples.
  • the “administration” of a wound dressing composition to a subject includes any route of introducing or delivering to a subject a diagnostic wound dressing composition to perform its intended function. Administration can be carried out by any suitable route, including but not limited to, topical administration. Administration includes self-administration and the administration by another.
  • biofilm refers to an association of microorganisms, e.g., single or multiple species, that can be encased or embedded in a matrix material, which may be self-produced by resident microorganisms.
  • the biofilm may be present or adhere to living and/or non-living surfaces, e.g., tissue, a wound, medical implants, such as but not limited to orthopedic implants, dental implants, catheters, stents and so on.
  • Exemplary microorganisms include, but are not limited to bacteria, e.g., Gram-negative bacteria, such as Pseudomonas aeruginosa, Gram-positive bacteria, such as Staphylococcus aureus and Streptococcus mutans, and fungi, such as yeasts, e.g., Candida albicans.
  • the term “matrix material” is intended to encompass extracellular polymeric substances.
  • Exemplary matrix materials include, but are not limited to polysaccharides, glycoproteins and/or nucleic acids.
  • biofilm is further intended to include biological films that develop and persist at interfaces in aqueous environments.
  • biofilm development or “biofilm formation” is intended to include the formation, growth, and modification of the bacterial colonies contained with biofilm structures, as well as the synthesis and maintenance of the exopolysaccharide of the biofilm structures.
  • “Reducing” or “disrupting” a biofilm includes reducing the number of total viable microorganisms making up at least part of the biofilm, for example, as measured by total viable counts (TVC) of microorganisms (e.g., bacteria, yeast).
  • TVC total viable counts
  • the term “effective amount” refers to a quantity sufficient to achieve a desired therapeutic and/or prophylactic effect, e.g. , an amount which results in the decrease in a wound described herein or one or more signs or symptoms associated with a wound described herein.
  • the amount of a composition administered to the subject will vary depending on the composition, the degree, type, and severity of the wound and on the characteristics of the individual.
  • the compositions can also be administered in combination with one or more additional therapeutic compounds.
  • the therapeutic compositions may be administered to a subject having one or more wounds.
  • mammalian recombinant collagen refers to collagen manufactured by culturing a non-human organism or mammalian or non-mammalian cells to express at least one exogenous gene encoding a collagen in the culturing system.
  • human recombinant collagen refers to collagen manufactured by culturing a non-human organism or mammalian or non-mammalian cells to express at least one human gene encoding a collagen.
  • the human recombinant collagen may be selected from the group consisting of collagen type I, type II, type III, type IV, type V, type VI, type VII, type VIII, type IX, type X, type XI, type XII, type XIII, type XIV, type XV, type XVI, type XVII, type XVIII, type XIX, type XX, type XXI, type XXIII, type XXIV, type XXV, type XXVI, and type XXVII.
  • the human recombinant collagen can be collagen of one type free of any other type, or can be a mixture of collagen types.
  • the human recombinant collagen comprises collagens selected from the group consisting of collagen type I, collagen type III, and mixtures thereof.
  • the term "bovine recombinant collagen” refers to collagen manufactured by culturing a non-human organism or mammalian or non-mammalian cells to express at least one bovine gene encoding a collagen.
  • the bovine recombinant collagen may be selected from the group consisting of collagen type I, type II, type III, and type IV.
  • the bovine recombinant collagen can be collagen of one type free of any other type, or can be a mixture of collagen types.
  • the bovine recombinant collagen comprises collagens selected from the group consisting of collagen type I, collagen type III, and mixtures thereof.
  • molecular weight (also known as “relative molar mass”) is a dimensionless quantity but is converted to molar mass by multiplying by 1 gram/mole - for example, collagen with a weight-average molecular weight of 5,000 has a weight- average molar mass of 5,000 g/mol.
  • the terms “individual”, “patient”, or “subject” can be an individual organism, a vertebrate, a mammal, or a human. In some embodiments, the individual, patient or subject is a human.
  • Treating covers the treatment of a wound described herein, in a subject, such as a human, and includes: (i) inhibiting a wound, i.e., arresting its development; (ii) relieving a wound, i.e., causing regression of the wound; (iii) slowing progression of the wound; and/or (iv) inhibiting, relieving, or slowing progression of one or more symptoms of the wound.
  • treatment means that the symptoms associated with the wound are, e.g., alleviated, reduced, cured, or placed in a state of remission.
  • the various modes of treatment of wounds as described herein are intended to mean “substantial,” which includes total but also less than total treatment, and wherein some biologically or medically relevant result is achieved.
  • the treatment may be a continuous prolonged treatment for a chronic wound or a single, or few time administrations for the treatment of an acute wound.
  • a wound can become infected by microbes.
  • An infected wound is a wound in which bacteria or other microorganisms have significantly colonized to the extent of causing a deterioration and delay in the healing of the wound. Thus, a reduction in bacterial colonization is vital in wound therapy.
  • the present disclosure is directed, in part, to wound dressing compositions that include a microcapsule that includes an agent (such as an antimicrobial agent), that may treat and/or prevent infections in a wound upon application, and overtime.
  • an agent such as an antimicrobial agent
  • Certain embodiments of the wound dressing compositions of the present technology advantageously exhibit improved stability by encapsulating the antimicrobial agents in a polymer.
  • Certain embodiments of the microcapsules of the wound dressing compositions of the present technology are further be configured to provide a staged release of the wound modulating components.
  • a wound dressing composition includes about 30 wt.% to about 95 wt.% of a collagen with a weight-average molecular weight of about 5,000 to about 100,000, about 30 wt.% to about 70 wt.% oxidized regenerated cellulose (ORC) with a weight-average molecular weight of about 50,000 to about 1,000,000, and a microcapsule comprising an agent encapsulated in a polymer.
  • the wound dressing composition may be in the form of a foam or may be in the form of a casting film.
  • FIG. 1 provides a non-limiting image of an embodiment of a microcapsule of the present technology, where the particular amount of agent in the microcapsule was about 47 wt.%.
  • the wound dressing composition may include a plurality of microcapsules.
  • the microcapsules may have a diameter from about 0.02 pm to about 2,000 pm.
  • the microcapsules may have a diameter from about 0.02 pm, about 0.03 pm, about 0.04 pm, about 0.05 pm, about 0.06 pm, about 0.07 pm, about 0.08 pm, about 0.09 pm, about 0.1 pm, about 0.11 pm, about 0.12 pm, about 0.13 pm, about 0.14 pm, about 0.15 pm, about 0.16 pm, about 0.17 pm, about 0.18 pm, about 0.19 pm, about 0.2 pm, about 0.22 pm, about 0.24 pm, about 0.26 pm, about 0.28 pm, about 0.3 pm, about 0.32 pm, about 0.34 pm, about 0.36 pm, about 0.38 pm, about 0.4 pm, about 0.42 pm, about 0.44 pm, about 0.46 pm, about 0.48 pm, about 0.5 pm, about 0.55 pm, about 0.6 pm, about 0.65 pm, about
  • the microcapsules may have a diameter from about 100 pm to about 2,000 pm.
  • the diameter of the microcapsules of any embodiment disclosed herein may be a weight-average diameter.
  • the wound dressing composition may include about 0.5 wt.% to about 50 wt.% microcapsules. Additionally or alternatively, in some embodiments, the wound dressing composition may include about 1 wt.% to about 10 wt.% microcapsules.
  • the wound dressing composition may include microcapsules in an amount of about 0.5 wt.%, about 0.6 wt.%, about 0.7 wt.%, about 0.8 wt.%, about 0.9 wt.%, about 1 wt.%, about 2 wt.%, about 3 wt.%, about 4 wt.%, about 5 wt.%, about 6 wt.%, about 7 wt.%, about 8 wt.%, about 9 wt.%, about 10 wt.%, about 11 wt.%, about 12 wt.%, about 13 wt.%, about 14 wt.%, about 15 wt.%, about 16 wt.%, about 17 wt.%, about 18 wt.%, about 19 wt.%, about 20 wt.%, about 22 wt.%, about 24 wt.%, about 26 wt.%, about 28 wt.%, about 30
  • the microcapsule may include about 0.01 wt.% to about 40 wt.% of the agent based on the total weight of the microcapsule.
  • the microcapsule may include the agent in an amount (based on the total weight of the microcapsule) of about 0.01 wt.%, about 0.05 wt.%, about 0.1 wt.%, about 0.2 wt.%, about 0.3 wt.%, about 0.4 wt.%, about 0.5 wt.%, about 0.6 wt.%, about 0.7 wt.%, about 0.8 wt.%, about 0.9 wt.%, about 1 wt.%, about 2 wt.%, about 3 wt.%, about 4 wt.%, about 5 wt.%, about 6 wt.%, about 7 wt.%, about 8 wt.%, about 9 wt.%, about 10 wt.%, about 11
  • the microcapsules may be configured to release the agent(s) over a finite period of time, e g ., from about 2 days to about 14 days. Additionally or alternatively, in some embodiments, the microcapsules may be configured to release the agent(s) over a finite period of time that is greater than 10 days. Thus, the microcapsules may be configured to release the agent(s) over a period of time from about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 7 days, about 8 days, about 9 days, about 10 days, about 11 days, about 12 days, about 13 days, about 14 days, or any range including and/or in between any two of these values.
  • the polymer may include polyethylene glycol, polyvinyl alcohol, polyhydroxyethylmethacrylate, polylactic acid, chitosan, alginate, cellulose acetate, carrageenan, casein, gelatin, hyaluronic acid, silk, fibrin, dextrans, cyclodextrins, polycaprolactone, polyhydroxybutarate, polyhydroxyvalerate, poly(lactic-co-glycolic acid), or a combination of any two or more thereof.
  • the agent may include an antimicrobial agent, a signaling protein, an antioxidant, or a combination of any two or more thereof.
  • the antimicrobial agent may include acetic acid, benzoic acid, natamycin, nisin, citric acid, sorbic acid, polyhexamethylene biguanide, povidone iodine, propionic acid, honey, sulfites or any acid thereof, or a combination of any two or more thereof.
  • the signaling protein may include a platelet-derived growth factor (PDGF), a hepatocyte growth factor (HGF), a transforming growth factor beta (TGFP). a fibroblast growth factor (FGF), an epidermal growth factor (EGF), keratinocyte growth factor (KGF), Caveolin-1 (Cavl), or a combination of any two or more thereof.
  • PDGF platelet-derived growth factor
  • HGF hepatocyte growth factor
  • TGFP transforming growth factor beta
  • FGF fibroblast growth factor
  • EGF epidermal growth factor
  • KGF keratinocyte growth factor
  • Caveolin-1 Caveolin-1
  • the signaling protein may include fibroblast growth factor 1 (FGF1), fibroblast growth factor 2 (FGF2), fibroblast growth factor 3 (FGF3), fibroblast growth factor 4 (FGF4), fibroblast growth factor 5 (FGF5), fibroblast growth factor 6 (FGF6), fibroblast growth factor 7/keratinocyte growth factor (FGF7/KGF), fibroblast growth factor 8 (FGF8), fibroblast growth factor 9 (FGF9), fibroblast growth factor 10/keratinocyte growth factor 2 (FGF10/KGF2), fibroblast growth factor 11 (FGF11), fibroblast growth factor 12 (FGF12), fibroblast growth factor 13 (FGF13), fibroblast growth factor 14 (FGF14), fibroblast growth factor 15 (FGF15), fibroblast growth factor 16 (FGF16), fibroblast growth factor 17 (FGF17), fibroblast growth factor 18 (FGF18), fibroblast growth factor 19 (FGF19), fibroblast growth factor 20 (FGF1), fibroblast growth factor 2
  • the antioxidant may include anthocyanins, astaxanthin, bilirubin, canthaxanthin, capsaicin, citric acid, curcumin, coenzyme Q10, eugenol, flavanol, flavonolignans, flavanone, flavone, flavonol, iodide, isoflavone phytoestrogens, lutein, lycopene, manganese, melatonin, N-acetylcysteine, oxalic acid, phenolic acids, phytic acid, A-a-lipoic acid, stilbenoids, tocopherol, tocotrienol, vitamin A, vitamin C, vitamin E, xanthones, zeaxanthin, a- carotene, b-carotene, or a combination of any two or more thereof.
  • the anthocyanins may include, but are not limited to, cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin, or a combination of any two or more thereof.
  • the flavanols may include, but are not limited to, catechin, epicatechin, theaflavin, thearubigins, gallocatechin, epigallocatechin, a gallate ester of any thereof, or a combination of any two or more thereof.
  • the flavanones may include, but are not limited to, eriodictyol, hesperetin, naringenin, or a combination of any two or more thereof.
  • the flavones may include, but are not limited to, apigenin, luteolin, tangeritin, or a combination of any two or more thereof.
  • the flavonols may include, but are not limited to, isorhamnetin, kaempferol, myricetin, proanthocyanidins, quercetin, rutin, or a combination of any two or more thereof.
  • the isoflavone phytoestrogens may include, but are not limited to, daidzein, genistein, glycitein, or a combination of any two or more thereof.
  • the phenolic acids may include, but are not limited to, chicoric acid, chlorogenic acid, cinnamic acid, ellagic acid, ellagitannins, gallic acid, gallotannins, rosmarinic acid, salicylic acid, or any ester thereof, or a combination of any two or more thereof.
  • the stillbenoids may include, but are not limited to, resveratrol, pterostilbene, or a combination thereof.
  • the collagen may be recombinant or naturally occurring. Additionally or alternatively, in some embodiments, the collagen may be a mammalian collagen, an avian collagen, a reptilian collagen, an amphibian collagen, fish collagen, or a combination of any two or more thereof. Additionally or alternatively, in some embodiments, the collagen may be mammalian collagen. Additionally or alternatively, in some embodiments, the mammalian collagen may be a bovine collagen, an ovine collagen, a porcine collagen, a human collagen, or a combination of any two or more thereof. Additionally or alternatively, in some embodiments, the collagen may be a human collagen.
  • the human collagen may be human collagen type I, human collagen type III, or any combination thereof. Additionally or alternatively, in some embodiments, the collagen may be a bovine collagen. Additionally or alternatively, in some embodiments, the collagen may be bovine collagen type I, bovine collagen type II, bovine collagen type III, bovine collagen type IV, or a combination of any two or more thereof. Additionally or alternatively, in some embodiments, the collagen may be ovine collagen type I, ovine collagen type II, ovine collagen type III, ovine collagen type IV, or a combination of any two or more thereof.
  • the collagen may be porcine collagen type I, porcine collagen type II, porcine collagen type III, porcine collagen type IV, or a combination of any two or more thereof. Additionally or alternatively, in some embodiments, the collagen may be a combination of bovine collagen type I and bovine collagen type III. Additionally or alternatively, in some embodiments, the collagen may be type I human recombinant collagen, type III human recombinant collagen, type I bovine collagen, type II bovine collagen, or a combination of any two or more thereof.
  • the collagen may be provided by any manner known in the art. Additionally or alternatively, in some embodiments, the collagen may be provided by a tissue sample or recombinantly manufactured. Additionally or alternatively, in some embodiments, mammalian recombinant collagen may be provided by any suitable method known in the art. Additionally or alternatively, in some embodiments, human recombinant collagen may be provided by any suitable method known in the art. For example, the step of providing human recombinant collagen may comprise following the protocol described in U.S. Pat. No. 5,962,648, the entire content of which is incorporated herein by reference. Further recombinant processes are set forth in U.S. Pat. No.
  • collagen will be recombinantly manufactured by culturing a cell which has been transfected with at least one gene encoding a polypeptide comprising collagen and genes encoding oxidized cellulose and subunits of the post-translational enzyme prolyl 4- hydroxylase, and purifying the resultant collagen monomer therefrom.
  • collagen will be recombinantly manufactured by a plant (e.g., CollPlant, CollPlant Holdings Ltd., Ness Ziona, Israel) such as tobacco, or in yeast.
  • the human recombinant collagen solution may be subsequently subjected to polymerization or cross-linking conditions to produce an insoluble fibrous collagen.
  • the collagen may be a type I collagen, a type II collagen, or a type III collagen. Additionally or alternatively, in some embodiments, the collagen may be obtained from any natural source, may be chemically-modified collagen (e.g., an atelocollagen obtained by removing the immunogenic telopeptides from natural collagen), or may be any combination thereof.
  • the collagen may include collagen obtained from bovine corium that has been rendered largely free of non-collagenous components, for example, including fat, non- collagenous proteins, polysaccharides, and other carbohydrates, such as by procedures described in U.S. Pat. Nos. 4,614,794 and 4,320,201, the entire contents of which are incorporated by reference.
  • the wound dressing composition includes about 30 wt.% to about 95 wt.% of a collagen.
  • the collagen may be included in the wound dressing composition in an amount of about 1 wt.%, about 1.1 wt.%, about 1.2 wt.%, about 1.3 wt.%, about 1.4 wt.%, about 1.5 wt.%, about 1.6 wt.%, about 1.7 wt.%, about 1.8 wt.%, about 1.9 wt.%, about 2 wt.%, about 2.2 wt.%, about 2.4 wt.%, about 2.6 wt.%, about 2.8 wt.%, about 3 wt.%, about 3.2 wt.%, about 3.4 wt.%, about 3.6 wt.%, about 3.8 wt.%, about 4 wt.%, about 4.2 wt.%, about 4.4 wt.%, about 4.6 wt.%, about
  • the collagen may have a weight-average molecular weight of about 5,000 to about 100,000. Additionally or alternatively, in some embodiments, the collagen may have a weight-average molecular weight of about 5,000, about 6,000, about 7,000, about 8,000, about 9,000, about 10,000, about 11,000, about 12,000, about 13,000, about 14,000, about 15,000, about 16,000, about 17,000, about 18,000, about 19,000, about 20,000, about 22,000, about 24,000, about 26,000, about 28,000, about 30,000, about 32,000, about 34,000, about 36,000, about 38,000, about 40,000, about 42,000, about 44,000, about 46,000, about 48,000, about 50,000, about 52,000, about 54,000, about 56,000, about 58,000, about 60,000, about 62,000, about 64,000, about 66,000, about 68,000, about 70,000, about 72,000, about 74,000, about 76,000, about 78,000, about 80,000, about 82,000, about 84,000, about 86,000, about 88,000,
  • the collagen of the wound dressing composition may include a weight ratio of human collagen type I to human collagen type III of about 100:0, about 90: 10, about 80:20, about 70:30, about 60:40, about 50:50, about 40:60, about 30:70, about 20:80, about 10:90, about 0: 100, or any range including and/or in between any two of these values. Additionally or alternatively, in some embodiments, the ratio by weight of human collagen type I to human collagen type III is greater than about 50:50, or greater than about 70:30. Additionally or alternatively, in some embodiments, the collagen of the wound dressing composition may include a weight ratio of type I bovine collagen to type III bovine collagen of about 85:15.
  • oxidized regenerated cellulose may be produced by the oxidation of cellulose, for example with dinitrogen tetroxide and/or as described in U.S. Pat. No. 3,122,479 (incorporated herein by reference). Without wishing to be bound by theory, it is believed that this process may convert primary alcohol groups on the saccharide residues of the cellulose to carboxylic acid groups, for example, forming uronic acid residues within the cellulose chain. The oxidation may not proceed with complete selectivity, and as a result hydroxyl groups on carbons 2 and 3 of the saccharide residue may be converted to the keto form.
  • ORC is available with a variety of degrees of oxidation and hence rates of degradation.
  • the ORC may include particles, fibers, or both; in any embodiment disclosed herein, the ORC may be in the form of particles, such as fiber particles or powder particles
  • the wound dressing composition may include from about 30 wt.% to about 70 wt.% of ORC.
  • ORC may be included in the wound dressing composition in an amount of about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 46 wt.%, about 48 wt.%, about 50 wt.%, about 52 wt.%, about 54 wt.%, about 56 wt.%, about 58 wt.%, about 60 wt.%, about 62 wt.%, about 64 wt.%, about 66 wt.%, about 68 wt.%, about 70 wt.%, or any range including and/or in between any two of these values.
  • the ORC may have a weight-average molecular weight of about 50,000 to about 1,000,000.
  • the ORC may have a weight-average molecular weight of about 50,000, about 55,000, about 60,000, about 65,000, about 70,000, about 75,000, about 80,000, about 85,000, about 90,000, about 95,000, about 100,000, about 110,000, about 120,000, about 130,000, about 140,000, about 150,000, about 160,000, about 170,000, about 180,000, about 190,000, about 200,000, about 210,000, about 220,000, about 230,000, about 240,000, about 250,000, about 260,000, about 270,000, about 280,000, about 290,000, about 300,000, about 310,000, about 320,000, about 330,000, about 340,000, about 350,000, about 360,000, about 370,000, about 380,000, about 390,000, about 400,000, about 410,000, about 420,000, about 430,000, about 440,000, about 450,000, about 460,000, about 470,000, about 480,000, about 4
  • the ORC may include particles, fibers, or both; in any embodiment disclosed herein, the ORC may be in the form of particles, such as fiber particles or powder particles. In embodiments that include ORC fibers, the ORC fibers may have a volume fraction such that at least 80% of the fibers have lengths in the range from about 5 pm to about 1,000 pm.
  • the ORC may include fiber lengths of about 5 pm, about 6 pm, about 7 pm, about 8 pm, about 9 pm, about 10 mih, about 11 mih, about 12 mhi, about 13 mih, about 14 mhi, about 15 mih, about 16 mhi, about 17 mhi, about 18 mhi, about 19 mhi, about 20 mhi, about 22 mhi, about 24 mhi, about 26 mhi, about 28 mhi, about 30 mhi, about 32 mhi, about 34 mhi, about 36 mih, about 38 mhi, about 40 mhi, about 42 mhi, about 44 pm, about 46 mih, about 48 mhi, about 50 mih, about 55 mhi, about 60 mhi, about 65 mih, about 70 pm, about 75 mih, about 80 mhi, about 85 mih, about 90 mhi, about 95 mhi, about
  • the wound dressing composition may include a weight ratio of collagen to ORC of about 60:40 to about 40:60.
  • the wound dressing composition may include a weight ratio of collagen to ORC of about 60:40, about 59:41, about 58:42, about 57:43, about 56:44, about 55:45, about 54:46, about 53:47, about 52:48, about 51:49, about 50:50, about 49:51, about 48:52, about 47:53, about 46:54, about 45:55, about 44:56, about 43:57, about 42:58, about 41:59, about 40:60, or any range including and/or in between any two of these values.
  • the weight ratio of the collagen to ORC may be about 55:45.
  • the wound dressing composition may have a thickness of about 0.5 mm to about 5 mm.
  • the wound dressing composition may have a thickness of about 0.5 cm, about 0.6 cm, about 0.7 cm, about 0.8 cm, about 0.9 cm, about 1 cm, about 1.1 cm, about 1.2 cm, about 1.3 cm, about 1.4 cm, about 1.5 cm, about 1.6 cm, about 1.7 cm, about 1.8 cm, about 1.9 cm, about 2 cm, about 2.1 cm, about 2.2 cm, about 2.3 cm, about 2.4 cm, about 2.5 cm, about 2.6 cm, about 2.7 cm, about 2.8 cm, about 2.9 cm, about 3 cm, about 3.1 cm, about 3.2 cm, about 3.3 cm, about 3.4 cm, about 3.5 cm, about 3.6 cm, about 3.7 cm, about 3.8 cm, about 3.9 cm, about 4 cm, about 4.1 cm, about 4.2 cm, about 4.3 cm, about 4.4 cm, about 4.5 cm, about 4.6 cm, about 4.7 cm, about
  • the wound dressing composition may have a solid content of about 0.1 wt.% to about 100 wt.%, such as about 0.1 wt.% to about 10 wt.%.
  • the wound dressing composition may have a solid content of about 0.1 wt.%, about 0.11 wt.%, about 0.12 wt.%, about 0.13 wt.%, about 0.14 wt.%, about 0.15 wt.%, about 0.16 wt.%, about 0.17 wt.%, about 0.18 wt.%, about 0.19 wt.%, about 0.2 wt.%, about 0.22 wt.%, about 0.24 wt.%, about 0.26 wt.%, about 0.28 wt.%, about 0.3 wt.%, about 0.32 wt.%, about 0.34 wt.%, about 0.36 wt.%, about 0.38 wt.%, about 0.4
  • the wound dressing composition may include a silver compound. Additionally or alternatively, in some embodiments, the wound dressing composition may include about 0.1 wt.% to about 3 wt.% of the silver compound. Thus, the silver compound may be included in the wound dressing composition in an amount of about 0.1 wt.%, about 0.11 wt.%, about 0.12 wt.%, about 0.13 wt.%, about 0.14 wt.%, about 0.15 wt.%, about 0.16 wt.%, about 0.17 wt.%, about 0.18 wt.%, about 0.19 wt.%, about 0.2 wt.%, about 0.22 wt.%, about 0.24 wt.%, about 0.26 wt.%, about 0.28 wt.%, about 0.3 wt.%, about 0.32 wt.%, about 0.34 wt.%, about 0.36 wt.%, about 0.38 wt.%
  • the silver compound may be one or more pharmaceutically acceptable salts.
  • the one or more pharmaceutically acceptable silver salts may include, but are not limited to, silver oxide, silver chromate, silver allantoinate, silver borate, silver glycerolate, silver nitrate, silver acetate, silver chloride, silver sulfate, silver lactate, silver bromide, silver iodide, silver carbonate, silver citrate, silver laurate, silver deoxycholate, silver salicylate, silver -aminobenzoate, silver / -aminosalicylatc. nanocrystalline silver, any pharmaceutically acceptable salt thereof, a silver oxysalt (e.g., Ag7NOn), or a combination of any two or more thereof
  • a silver oxysalt e.g., Ag7NOn
  • the wound dressing composition of the present technology may be capable of preventing, reducing, inhibiting, or dismpting biofilm formation in a wound.
  • Reducing a biofilm includes reducing the number of total viable microorganisms making up at least part of the biofilm, for example, as measured by total viable counts (TVC) of microorganisms (e.g., bacteria, yeast).
  • the biofilm may comprise bacteria including, but not limited to, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus mutans.
  • the biofilm may also include fungi including but not limited to yeasts, such as Candida albicans.
  • the wound dressing composition of the present technology may be capable of preventing, reducing, inhibiting, or dismpting a biofilm in a wound by > about 10% to about 100%, after 24 hours in vitro exposure. Additionally or alternatively, in some embodiments, the wound dressing composition of the present technology may be capable of preventing, reducing, inhibiting, or dismpting a biofilm in a wound by about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, about 100%, or any range including and/or in between any two of these values.
  • Certain embodiments of the therapeutic efficacy of the wound dressing composition of the present technology are assayed using any method known to those in the art.
  • An exemplary method to test the therapeutic efficacy of the wound dressing composition of the present technology is the colony drip flow reactor (C-DFR) assay (see Lipp, C., etal., J. Wound Care, 19:220-226(2010), which is incorporated herein by reference).
  • C-DFR colony drip flow reactor
  • the wound dressing composition of the present disclosure may be sterile and packaged in a microorganism-impermeable container.
  • a 2 weight % slurry of collagen (55 % by weight) and ORC (45 % by weight) is prepared in an acetic acid solution (0.5 M).
  • the suspension was mixed for at least 15 minutes to ensure uniform mixing.
  • microcapsules containing desired cargo is added to this mixture.
  • the capsules are synthesized using coaxial nozzle technique using a 100 to 1000 micron diameter nozzle with oscillating frequency ranging from 100 to 2000 Hz at a inlet pressure ranging from 10 to 400 mbar.
  • the mixture containing collagen, ORC, and encapsulated cago was briefly stirred for uniform mixing and subsequently degassed. The mixture was then poured into freeze drying trays.
  • the wound dressing composition of any embodiment described herein may be employed in therapy in which a wound is treated with reduced pressure.
  • Treatment of tissue with reduced pressure may be commonly referred to as “negative-pressure therapy,” but is also known by other names, including “negative-pressure wound therapy,” “reduced-pressure therapy,” “vacuum therapy,” “vacuum-assisted closure,” and “topical negative-pressure,” for example.
  • Negative-pressure therapy may provide a number of benefits, including migration of epithelial and subcutaneous tissues, improved blood flow, and/or micro-deformation of tissue at a wound site. Together, these benefits may increase development of granulation tissue and reduce healing times.
  • the system may be configured to provide negative-pressure to a wound in accordance with this specification.
  • the system may generally include a negative-pressure supply, and may include or be configured to be coupled to a distribution component.
  • a distribution component may refer to any complementary or ancillary component configured to be fluidly coupled to a negative-pressure supply in a fluid path between a negative- pressure supply and a wound.
  • the wound dressing composition may be configured to distribute negative pressure.
  • the wound dressing composition may comprise or be configured as a manifold.
  • a “manifold” in this context generally includes any composition or structure providing a plurality of pathways configured to collect or distribute fluid across a wound under pressure.
  • a manifold may be configured to receive negative pressure from the negative-pressure source and to distribute negative pressure through multiple apertures ( e.g ., pores), which may have the effect of collecting fluid and drawing the fluid toward the negative-pressure source.
  • the fluid path(s) may be reversed or a secondary fluid path may be provided to facilitate movement of fluid across a wound.
  • a manifold may be interconnected to improve distribution or collection of fluids.
  • a manifold may be a porous material having a plurality of interconnected cells or pores.
  • open-cell foams such as reticulated foams may generally include pores, edges, and/or walls that may form interconnected fluid pathways (such as channels).
  • the fluid mechanics associated with using a negative-pressure source to reduce pressure in another component or location, such as within a sealed therapeutic environment, can be mathematically complex.
  • the basic principles of fluid mechanics applicable to negative-pressure therapy are generally well-known to those skilled in the art.
  • the process of reducing pressure may be described generally and illustratively herein as “delivering,” “distributing,” or “generating” negative pressure, for example.
  • a fluid such as wound fluid (for example, wound exudates and other fluids) flows toward lower pressure along a fluid path.
  • wound fluid for example, wound exudates and other fluids
  • downstream typically implies something in a fluid path relatively closer to a source of negative pressure or further away from a source of positive pressure.
  • upstream implies something relatively further away from a source of negative pressure or closer to a source of positive pressure. This orientation is generally presumed for purposes of describing various features and components herein.
  • the fluid path may also be reversed in some applications (such as by substituting a positive-pressure source for a negative-pressure source) and this descriptive convention should not be construed as a limiting convention.
  • Negative pressure may generally refer to a pressure less than a local ambient pressure, such as the ambient pressure in a local environment external to a sealed therapeutic environment provided by the wound dressing composition.
  • the local ambient pressure may also be the atmospheric pressure proximate to or about a wound.
  • the pressure may be less than a hydrostatic pressure associated with the tissue at the wound.
  • the pressure is generally a low vacuum, also commonly referred to as a rough vacuum, between -5 mm Hg (-667 Pa) and -500 mm Hg (-66.7 kPa), gauge pressure.
  • Common therapeutic ranges are between -50 mm Hg (- 6.7 kPa) and -300 mm Hg (-39.9 kPa), gauge pressure.
  • a negative-pressure supply may be a reservoir of air at a negative pressure, or may be a manual or electrically-powered device that can reduce the pressure in a sealed volume, such as a vacuum pump, a suction pump, a wall suction port available at many healthcare facilities, or a micro-pump, for example.
  • a negative-pressure supply may be housed within or used in conjunction with other components, such as sensors, processing units, alarm indicators, memory, databases, software, display devices, or user interfaces that further facilitate therapy.
  • a negative-pressure source may be combined with a controller and other components into a therapy unit.
  • a negative-pressure supply may also have one or more supply ports configured to facilitate coupling and de-coupling of the negative-pressure supply to one or more distribution components.
  • components may be fluidly coupled to each other to provide a path for transferring fluids (i.e., liquid and/or gas) between the components.
  • components may be fluidly coupled through a fluid conductor, such as a tube.
  • a fluid conductor may include a tube, pipe, hose, conduit, or other structure with one or more lumina or open passages adapted to convey a fluid between two ends thereof.
  • a fluid conductor may be an elongated, cylindrical structure with some flexibility, but the geometry and rigidity may vary.
  • the negative-pressure source may be operatively coupled to the wound dressing composition via a dressing interface.
  • the method includes administering to the wound a wound dressing composition of any embodiment disclosed herein.
  • the wound may be an acute wound or a chronic wound.
  • Exemplary chronic wounds include, but are not limited to, infectious wounds, venous ulcers, decubitis ulcers, and/or diabetic ulcers; exemplary acute wounds include, but are not limited to, surgical wounds, trauma wounds, bum wounds, and/or donor sites.
  • the wound dressing composition may protect the wound from infection.
  • the infection may be a bacterial infection or a fungal infection.
  • the bacterial infection may be caused by gramnegative or gram-positive bacteria.
  • the subject may be a mammal, such as a human.
  • Examples of gram-positive bacteria include, but are not limited to, Actinomyces sp., Arcanobacterium sp., Bacillus sp., Bavariicoccus sp., Brachybacterium sp., Clostridium sp., Cnuibacter sp., Corynebacterium sp., Enterococcus sp., Desulfitobacterium sp., Fervidobacterium sp., Georgenia sp., Janibacter sp., Lactobacillales sp.,Microbispora sp., Nocardia sp., Pasteuria sp., Pilibacter sp., Propionibacterium sp., Rathayibacter sp., Rhodococcus sp., Roseburia sp., Rothia sp., Sarcina sp., Solibacillus sp., Sporosarcina s
  • Syntrophomonas sp. or Tepidibacter sp.
  • Examples of gram-negative bacteria include, but are not limited to, Acetobacter sp., Acidaminococcus sp. , Acinetobacter sp., Agrobacterium sp., Akkermansia sp., Anaerobiospirillum sp., Anaerolinea sp., Arcobacter sp., Armatimonas sp., Azotobacter sp., Bacteroides sp., Bacteroidetes sp., Bartonella sp., Bdellovibriosp., Brachyspira sp., Bradyrhizobium sp., Caldilinea sp., Cardiobacterium sp., Christensenella sp., Chthonomonas sp., Coxiella sp., Cyanobacteria sp., Cytophaga sp.,
  • Dehalo genimonas sp. De sulfur obacterium sp., Devosia sp., Dialister sp., Dictyoglomus sp., Dinoroseobacter sp., Enterobacter sp., Escherichia sp., Fimbriimonas sp., Flavobacterium sp., Francisella sp., Fusobacterium sp., Gluconacetobacter sp., Haemophilus sp., Helicobacter sp., Kingella sp., Klebsiella sp., Kluyvera sp., Kozakia sp., Legionella sp.
  • Shimwellia sp. Sphingomonas sp., Stenotrophomonas sp., Thorselliaceae sp., V ampirococcus sp., Verminephrobacter sp., Vibrio sp., Victivallis sp., Vitreoscilla sp., Wolbachia sp.
  • the infection may be caused by Aspergillus sp., Aureobasidium sp., Candida sp., Cladosporium sp., Curvularia sp., Engodontium sp., Epicoccum sp., Gibberella sp., Hypocreales sp., Leptosphaerulina sp.,Malessezia sp., Penicillium sp., Rhodosporidium sp., Trichosporon sp., Trichtophyton sp., and Ulocladium sp.
  • the wound may include a biofilm, and the wound dressing composition of the present technology prevents, reduces, inhibits, or disrupts the biofdm.
  • the wound dressing composition may be administered directly to the wound. Any method known to those in the art for administering a wound dressing composition to an acute or a chronic wound disclosed herein may be employed. Suitable methods include in vitro or in vivo methods. In vivo methods typically include the administration of one or more wound dressing compositions to a subject in need thereof, suitably a human. When used in vivo for therapy, the one or more wound dressing compositions described herein are administered to the subject in effective amounts (i.e., amounts that have desired therapeutic effect). The dose and dosage regimen will depend upon the state of the wound of the subject, and the characteristics of the particular wound dressing composition used.
  • the effective amount may be determined during pre-clinical trials and clinical trials by methods familiar to physicians and clinicians.
  • An effective amount of one or more wound dressing compositions useful in the methods may be administered to a subject in need thereof by any number of well-known methods for administering wound dressing compositions.
  • the wound dressing compositions may be administered daily for 1 hour or more, for 2 hours or more, for 3 hours or more, for 4 hours or more, for 5 hours or more, for 6 hours or more, for 12 hours or more, or for 24 hours or more.
  • the wound dressing compositions may be administered one, two, three, four, or five times per day.
  • the wound dressing compositions may be administered daily for one, two, three, four or five weeks.
  • a wound dressing composition of any embodiment disclosed herein may be administered daily, where each daily administrating includes administering the wound dressing composition for 24 hours.
  • the wound dressing compositions may be administered daily for less than 6 weeks.
  • the wound dressing compositions may be administered daily for 6 weeks or more. In any embodiment disclosed herein, the wound dressing compositions may be administered daily for 12 weeks or more. In any embodiment disclosed herein, the wound dressing compositions may be administered every day, every other day, every third day, every fourth day, every fifth day, or every sixth day. In any embodiment disclosed herein, the wound dressing compositions may be administered weekly, bi-weekly, tri-weekly, or monthly. In any embodiment disclosed herein, the wound dressing compositions may be administered for a period of one, two, three, four, or five weeks. In any embodiment disclosed herein, the wound dressing compositions may be administered for six weeks or more. In any embodiment disclosed herein, the wound dressing compositions may be administered for twelve weeks or more.
  • the wound dressing compositions may be administered for a period of less than one year. In any embodiment disclosed herein, the wound dressing compositions may be administered for a period of more than one year. In any embodiment disclosed herein, the wound dressing compositions may be administered for an acute or chronic wound as appropriate.
  • the process may further include employing the wound dressing in the context of a negative-pressure therapy, where the negative-pressure therapy may include positioning the wound dressing composition proximate to the wound.
  • the various components of the wound dressing composition may be positioned with respect to the wound sequentially or, alternatively, may be positioned with respect to each other and then positioned with respect to the wound.
  • the negative-pressure therapy may further comprise sealing the wound dressing composition to tissue surrounding the wound to form a sealed space.
  • the wound dressing composition may be positioned proximate to the wound and sealed to an attachment surface near the wound, for example, to undamaged epidermis peripheral to a wound.
  • the negative-pressure therapy method in any embodiment herein may further include fluidly coupling a negative-pressure source to the sealed space and operating the negative-pressure source to generate a negative pressure in the sealed space.
  • the negative-pressure source may be coupled to the wound dressing composition such that the negative -pressure source may be used to reduce the pressure in the sealed space.
  • negative pressure applied across the wound, for example, via the wound dressing composition may be effective to induce macrostrain and microstrain at the wound, as well as remove exudates and other fluids from the wound.
  • the present technology also provides a method of preventing formation of a biofilm or reducing biofilm at a wound, where the method includes applying a wound dressing composition of any embodiment herein of the present technology adjacent to the wound.
  • kits that include a wound dressing composition of any embodiment described herein and instructions for use.
  • the kits of the present technology may also include instructions for methods for treating a wound in a subject in need thereof.
  • the kit may optionally comprise components such as antiseptic wipes, ointment, adhesive tape, tweezers, scissors, etc.
  • Example 1 Making the Microcapsules of the Present Technology
  • Exemplary microcapsules were synthesized using a co-axial nozzle technique. Specifically, antimicrobial additive containing solution is passed through the inner nozzle and alginate based solution is passed through the outer nozzle with nozzle diameter ranging between 100 to 1000 micron, voltage ranging from 1000 to 2500 V, vibrating frequency ranging from 100 to 2000 Hz, and inlet fluid flow pressure ranging from 100 to 400 mbarto obtain a final capsule with diameters ranging from 100 to 2000 microns by means of alginate crosslinking using Ca +2 ions.
  • Such exemplary microcapsules are illustrated in FIGs. 2-5, illustrating exemplary microcapsules formed via a 750 pm nozzle (FIG. 2), a 300 pm nozzle (FIG. 3), a 200 pm nozzle (FIG. 4), and a 450 pm nozzle (FIG. 5).
  • Example 2 Disrupting Bio films in a Wound
  • a wound dressing composition of any embodiment described herein will be administered directly to a chronic wound.
  • a first biofilm level will be determined using the colony drip flow reactor (C-DFR), described herein.
  • a second biofilm level will be determined 72 hours after administering the wound dressing composition to the wound. It is anticipated that administration of the wound dressing composition of the present technology to a chronic wound will result in the prevention, reduction, inhibition, or disruption of biofilm levels in the wound.
  • Example 3 Improved Collasen Synthesis Upon Application of the Wound Dressing Compositions of the Present Technology
  • a collagen synthesis assay with dermal fibroblasts is performed. This is a standard assay which shows the amount of collagen synthesized by fibroblasts after stimulation with the active agents in the wound dressing compositions of the present technology. Briefly, 8.4x 10 4 human fibroblasts (per well) are plated into 24-well plates, and then incubated at 37° C, 5% CO2, in 10% FBS-DMEM. Once the cells are confluent (within 24 hours of plating), the 10% FBS-DMEM is removed, and the cells are washed 3 c with serum -free DMEM (SF-DMEM), before the test dressing samples of the present technology or a collagen/ORC alone dressing is added to the cells.
  • SF-DMEM serum -free DMEM
  • Cells are then incubated for 72 hours after which time the media is collected and analyzed for the levels of the C-terminal propeptide of Type- 1 Collagen (Cl CP) present in the cell culture media.
  • the level of Cl CP in the media which is released by the fibroblasts as a by-product of collagen synthesis, is proportional to the level of collagen synthesis and so its level will be used to determine the level of collagen synthesis. It is anticipated that the wound dressing compositions of the present technology will exhibit increased collagen synthesis and/or improved wound healing of chronic or acute wounds compared to a standard collagen/ORC dressing.
  • the dressings of the present technology are useful in methods for treating a wound in a subject in need thereof, wherein the method comprises administering to the wound a dressing of any embodiment disclosed herein.
  • a range includes each individual member.
  • a group having 1-3 cells refers to groups having 1, 2, or 3 cells.
  • a group having 1-5 cells refers to groups having 1, 2, 3, 4, or 5 cells, and so forth.

Abstract

La présente invention concerne de manière générale des compositions de pansement qui comprennent des microcapsules, les microcapsules comprenant un ou plusieurs agents. Les compositions de pansement comprennent un mélange d'un collagène, d'une cellulose régénérée oxydée (ORC) et d'une microcapsule qui comprend au moins un agent. L'invention concerne également des kits comprenant les compositions de pansement de la présente technologie, et des instructions d'utilisation.
PCT/IB2021/053808 2020-05-29 2021-05-05 Encapsulation d'agents antimicrobiens pour pansements perfectionnés WO2021240271A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115154589A (zh) * 2022-08-26 2022-10-11 山东大学 白藜芦醇联合成纤维细胞生长因子1在缓解蒽环类药物诱导的心脏及肝脏毒性中的应用
CN115418032A (zh) * 2022-09-19 2022-12-02 安徽农业大学 一种Carr/BIL膜的制备方法
CN115531600A (zh) * 2022-07-21 2022-12-30 海南医学院 一种白藜芦醇胶束创伤敷料及其制备方法

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3122479A (en) 1957-11-14 1964-02-25 David F Smith Hemostatic surgical dressings
US4320201A (en) 1979-10-27 1982-03-16 Firma Carl Freudenberg Method for making collagen sponge for medical and cosmetic uses
US4614794A (en) 1983-10-04 1986-09-30 Johnson & Johnson Protein/polysaccharide complexes
US5593859A (en) 1991-10-23 1997-01-14 Thomas Jefferson University Synthesis of human procollagens and collagens in recombinant DNA systems
GB2311027A (en) * 1996-03-15 1997-09-17 Johnson & Johnson Medical Coated bioabsorbable beads for wound treatment
US5962648A (en) 1993-01-28 1999-10-05 Cohesion Technologies, Inc. Production of human recombinant collagen in the milk of transgenic mammals
WO2004078120A2 (fr) 2003-02-28 2004-09-16 Fibrogen, Inc. Compositions et biomateriaux de collagene
US20070142762A1 (en) * 2005-12-16 2007-06-21 Eastman Kodak Company Wound dressing
WO2019126368A1 (fr) * 2017-12-20 2019-06-27 Kci Usa, Inc. Pansement comprenant un tissu placentaire déshydraté pour la cicatrisation des plaies

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3122479A (en) 1957-11-14 1964-02-25 David F Smith Hemostatic surgical dressings
US4320201A (en) 1979-10-27 1982-03-16 Firma Carl Freudenberg Method for making collagen sponge for medical and cosmetic uses
US4614794A (en) 1983-10-04 1986-09-30 Johnson & Johnson Protein/polysaccharide complexes
US5593859A (en) 1991-10-23 1997-01-14 Thomas Jefferson University Synthesis of human procollagens and collagens in recombinant DNA systems
US5962648A (en) 1993-01-28 1999-10-05 Cohesion Technologies, Inc. Production of human recombinant collagen in the milk of transgenic mammals
GB2311027A (en) * 1996-03-15 1997-09-17 Johnson & Johnson Medical Coated bioabsorbable beads for wound treatment
WO2004078120A2 (fr) 2003-02-28 2004-09-16 Fibrogen, Inc. Compositions et biomateriaux de collagene
US20070142762A1 (en) * 2005-12-16 2007-06-21 Eastman Kodak Company Wound dressing
WO2019126368A1 (fr) * 2017-12-20 2019-06-27 Kci Usa, Inc. Pansement comprenant un tissu placentaire déshydraté pour la cicatrisation des plaies

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
LIPP, C. ET AL., J WOUND CARE, vol. 19, 2010, pages 220 - 226

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115531600A (zh) * 2022-07-21 2022-12-30 海南医学院 一种白藜芦醇胶束创伤敷料及其制备方法
CN115531600B (zh) * 2022-07-21 2023-08-25 海南医学院 一种白藜芦醇胶束创伤敷料及其制备方法
CN115154589A (zh) * 2022-08-26 2022-10-11 山东大学 白藜芦醇联合成纤维细胞生长因子1在缓解蒽环类药物诱导的心脏及肝脏毒性中的应用
CN115154589B (zh) * 2022-08-26 2024-04-09 山东大学 白藜芦醇联合成纤维细胞生长因子1在缓解蒽环类药物诱导的心脏及肝脏毒性中的应用
CN115418032A (zh) * 2022-09-19 2022-12-02 安徽农业大学 一种Carr/BIL膜的制备方法
CN115418032B (zh) * 2022-09-19 2023-03-14 安徽农业大学 一种Carr/BIL膜的制备方法

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