CN115418796A - Antibacterial fiber membrane and preparation method thereof - Google Patents

Antibacterial fiber membrane and preparation method thereof Download PDF

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Publication number
CN115418796A
CN115418796A CN202211117206.3A CN202211117206A CN115418796A CN 115418796 A CN115418796 A CN 115418796A CN 202211117206 A CN202211117206 A CN 202211117206A CN 115418796 A CN115418796 A CN 115418796A
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component
antibacterial
antibacterial agent
composition
mass ratio
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邓扬
刘赣
刘光元
李洋
傅岳龙
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Baida Liankang Biotechnology Shenzhen Co ltd
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Baida Liankang Biotechnology Shenzhen Co ltd
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Publication of CN115418796A publication Critical patent/CN115418796A/en
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    • DTEXTILES; PAPER
    • D04BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04HMAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
    • D04H1/00Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/70Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
    • D04H1/72Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged
    • D04H1/728Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged by electro-spinning
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/46Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01DMECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00Formation of filaments, threads, or the like
    • D01D5/0007Electro-spinning
    • D01D5/0015Electro-spinning characterised by the initial state of the material
    • D01D5/003Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01FCHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F1/00General methods for the manufacture of artificial filaments or the like
    • D01F1/02Addition of substances to the spinning solution or to the melt
    • D01F1/10Other agents for modifying properties
    • D01F1/103Agents inhibiting growth of microorganisms
    • DTEXTILES; PAPER
    • D04BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04HMAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
    • D04H1/00Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/40Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties
    • D04H1/42Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties characterised by the use of certain kinds of fibres insofar as this use has no preponderant influence on the consolidation of the fleece
    • D04H1/4326Condensation or reaction polymers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents

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  • Engineering & Computer Science (AREA)
  • Textile Engineering (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Dispersion Chemistry (AREA)
  • Mechanical Engineering (AREA)
  • Manufacturing & Machinery (AREA)
  • Hematology (AREA)
  • Materials Engineering (AREA)
  • General Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

An antibacterial fiber membrane and a preparation method thereof, the method comprises the following steps: a spraying step of spraying a composition onto a coating film formation object to form the fiber film; the composition comprises a component (A), a component (B), a component (C) and a component (D); the ingredient (a) comprises a volatile material; the component (B) comprises a hydrophobic polymer having a fiber film-forming ability and being soluble in the volatile substance; the component (C) comprises a surfactant; the component (D) contains an antibacterial agent. The electrospun membrane prepared by the invention has very good skin adhesion, mechanical property and the like. The invention can also be added with a low-toxicity and high-efficiency antibacterial agent as an antibacterial component, has no irritation and low side effect, and has high-efficiency antibacterial and wound healing promoting effects.

Description

Antibacterial fiber membrane and preparation method thereof
Technical Field
The invention relates to the technical field of medical wound dressings, in particular to an in-situ electrostatic spinning nanofiber membrane with an antibacterial effect for wound healing and a preparation method thereof.
Background
As a global medical problem, the difficulty of rapid and complete wound healing remains a serious clinical challenge. Traditional wound dressings such as bandages, gauze, absorbent cotton, etc. have been unable to meet the needs of modern people for wound care, merely as barriers to physical protection to aid healing. One of the common problems that make it difficult to heal a wound quickly and completely is infection of the wound. The conventional technique is mainly to add antibacterial drugs and materials to the dressing. Whereas conventional dressings consist primarily of aqueous materials such as hydrogels, or oily materials such as ointments. The former is generally thought to help the wound create a moist environment to promote skin healing and reduce scar tissue formation, however, the disadvantages of these materials in terms of air permeability, water permeability, barrier properties and durability often result in infection or adhesion of the wound, requiring frequent replacement, which often results in secondary injury or infection of the wound. The oily material of the latter is not beneficial to the release of a plurality of medicines on the wound part, thereby greatly reducing the effective medicine concentration on the wound part, causing the drug resistance of bacteria and delaying the wound healing. Meanwhile, most of the two materials are difficult to stay for a long time in the wound and are easy to be stained with clothes, so that frequent dressing change is difficult to avoid, and secondary injury or secondary infection is easy to occur due to frequent dressing change.
In recent years, nanofiber membranes prepared by electrospinning show great application prospects in being used as wound healing dressings. In addition to providing the physical protection provided by the conventional dressings described above, the nanofiber membrane prepared by electrospinning has a specific pore size distribution that is capable of isolating bacteria, allowing water and oxygen to permeate, and promoting absorption of active ingredients after being closely attached to the skin. Many polymer materials with good biocompatibility are successfully used for preparing the nanofiber membrane through electrostatic spinning. However, when the nanofiber membrane formed in advance is used for treating wounds at some complicated positions, close fitting to the wounds cannot be achieved, and therefore, the effects of completely isolating bacteria and efficiently promoting healing are difficult to achieve. In addition, pre-formed dressings also require complex handling when used for therapy. Therefore, compared with the pre-formed dressing, the in-situ electrostatic spinning nanofiber membrane for the skin wound and the preparation technology thereof have greater advantages and urgent needs.
Besides the advantages, the in-situ electrospun fiber also has the characteristics of controllable fiber diameter, large specific surface area and the like, so that the antibacterial material can be better wrapped and released. Commonly used antimicrobial materials include quaternary ammonium salts, polyquaternary ammonium salts, silver ions, and other cationic or polycationic compounds. The film formed by the existing method has poor skin adhesion and mechanical property and cannot meet the use requirement.
Disclosure of Invention
According to a first aspect, in an embodiment, there is provided a method of making an antimicrobial fibrous membrane, comprising:
a spraying step of spraying a composition onto an object to be coated to form the fiber film;
the composition comprises a component (A), a component (B), a component (C) and a component (D);
the ingredient (a) comprises a volatile material;
the component (B) comprises a hydrophobic polymer having a fiber film-forming ability and being soluble in the volatile substance;
the component (C) comprises a surfactant;
the component (D) contains an antibacterial agent.
According to a second aspect, in an embodiment, there is provided an antimicrobial fibrous membrane produced by the method of any one of the first aspect.
According to a third aspect, in one embodiment, there is provided a composition comprising ingredient (a), ingredient (B), ingredient (C), and ingredient (D);
the ingredient (a) comprises a volatile material;
the component (B) comprises a hydrophobic polymer having a fiber film-forming ability and being soluble in the volatile substance;
the component (C) comprises a surfactant;
the component (D) contains an antibacterial agent.
According to the antibacterial fiber membrane and the preparation method thereof, the electrospun membrane prepared by the invention has very good skin adhesion, mechanical property and the like.
In one embodiment, the electrospun membrane of the present invention enables controlled release of an antimicrobial agent.
In one embodiment, the invention can also add low-toxicity and high-efficiency antibacterial agents such as polyguanidine cationic polymers as antibacterial components, has no irritation and low side effect, and has high-efficiency antibacterial and wound healing promotion effects.
Drawings
FIG. 1 is a schematic diagram of an embodiment of an antibacterial nanofiber membrane prepared by in-situ electrospinning of skin;
FIG. 2 is a scanning electron micrograph of a PVB + polyether + polybiguanide PHMB nanofiber film prepared in example 10;
FIG. 3 is a graph of the results of controlled release of PAPB in artificial sweat using PAPB-loaded fibrous membranes;
FIG. 4 is a graph showing the antimicrobial effect of Escherichia coli in PHMB-loaded PVB fiber membranes;
FIG. 5 is a graph of the antimicrobial efficacy of methicillin-resistant Staphylococcus aureus (MRSA) on a PVB fiber film loaded with PHMB;
FIG. 6 is a graph of the antimicrobial effect of Escherichia coli in PAPB loaded PVB fiber membranes;
FIG. 7 is a graph of the antimicrobial efficacy of methicillin-resistant Staphylococcus aureus (MRSA) in a PAPB-loaded PVB fiber film;
FIG. 8 is a graph showing the antibacterial effects of Escherichia coli and methicillin-resistant Staphylococcus aureus on PHMB-loaded PU fiber membranes.
Detailed Description
The present invention will be described in further detail with reference to the following detailed description and accompanying drawings. In the following description, numerous details are set forth in order to provide a better understanding of the present application. However, those skilled in the art will readily recognize that some of the features may be omitted in different instances or may be replaced by other materials, methods. In some instances, certain operations related to the present application have not been shown or described in detail in order to avoid obscuring the core of the present application from excessive description, and it is not necessary for those skilled in the art to describe these operations in detail, so that they may be fully understood from the description in the specification and the general knowledge in the art.
Furthermore, the features, operations, or characteristics described in the specification may be combined in any suitable manner to form various embodiments. Also, the various steps or actions in the method descriptions may be transposed or transposed in order, as will be apparent to one of ordinary skill in the art. Thus, the various sequences in the specification and drawings are for the purpose of describing certain embodiments only and are not intended to imply a required sequence unless otherwise indicated where such sequence must be followed.
The numbering of the components as such, e.g., "first", "second", etc., is used herein only to distinguish the objects as described, and does not have any sequential or technical meaning.
According to a first aspect, in an embodiment, there is provided a method of making an antimicrobial fibrous membrane, comprising:
a spraying step of spraying the composition onto a coating film formation object to form a fibrous film;
the composition comprises a component (A), a component (B), a component (C) and a component (D);
ingredient (a) comprises a volatile material;
the component (B) contains a hydrophobic polymer having a fiber film-forming ability and being soluble in a volatile substance;
component (C) comprises a surfactant;
ingredient (D) contains an antibacterial agent.
In one embodiment, the composition can be used as a spinning solution for in situ electrostatic spraying of a surface such as skin to form a fibrous film.
In one embodiment, the volatile material comprises at least one of an alcohol, water, an acid.
In one embodiment, the volatile material comprises at least one of ethanol, isopropanol, butanol, hexafluoroisopropanol, acetic acid, water.
In one embodiment, the hydrophobic polymer comprises at least one of polyvinyl butyral (PVB), polycaprolactone (PCL), polylactic acid (PLA), polylactic-co-glycolic acid (PLGA), polyamide, polyurethane (PU), zein (Zein), polytetrafluoroethylene, polyvinylidene fluoride, polypropylene, polyacrylate, polyethylene terephthalate, silicone rubber.
In one embodiment, the surfactant comprises a polyether surfactant.
In one embodiment, the polyether surfactant includes, but is not limited to, at least one of poloxamer, alcohol polymers.
In one embodiment, the poloxamer may have a molecular weight of 500-20000 Da, including but not limited to 500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10000, 11000, 12000, 13000, 14000, 15000, 16000, 17000, 18000, 19000, 20000. The molecular weight of the poloxamer is not limited, and poloxamers of any molecular weight are suitable for use in the present invention.
In one embodiment, the poloxamer includes, but is not limited to, at least one of poloxamer 101, poloxamer 181, poloxamer 124, poloxamer 188, poloxamer 407, and the like.
In one embodiment, the molecular weight of the alcohol polymer is less than or equal to 2000Da.
In one embodiment, the alcohol polymer includes, but is not limited to, at least one of polyethylene glycol (PEG), polypropylene glycol (PPG), polytetramethylene glycol (PTMG), poly (1,2-butanediol) (PBG).
In one embodiment, the polyethylene glycol includes, but is not limited to, PEG-8 (polyethylene glycol with a molecular weight of 400Da, CAS number 25322-68-3).
In one embodiment, the antimicrobial agent comprises at least one of a low-irritation antimicrobial agent and a high-irritation antimicrobial agent. The antibacterial agent suitable for use in the present invention is not limited.
In one embodiment, the low irritation antimicrobial agent includes, but is not limited to, a guanidine polymer.
In one embodiment, the guanidine polymers include, but are not limited to, biguanide polycationic antimicrobial agents.
In one embodiment, the guanidine polymers include, but are not limited to, at least one of polyhexamethylene guanidine (PHMG), polyhexamethylene biguanide (PH MB), polyaminopropyl biguanide (PAPB), and the like.
In one embodiment, the highly irritating antimicrobial agent includes, but is not limited to, at least one of quaternary ammonium salts, polyquaternary ammonium salts, cationic antimicrobial agents, and polycationic antimicrobial agents. Cations include, but are not limited to, silver ions. These are merely exemplary and any other low-irritation antimicrobial agent or high-irritation antimicrobial agent may be used in the present invention.
In one embodiment, the antimicrobial agent of the present invention may also be a highly irritating antimicrobial agent, including but not limited to organic polyquaterniums, which may be used in less irritating scenarios.
In one embodiment, ingredient (B) comprises 5 to 50% by weight of the composition, including but not limited to 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, and the like.
In one embodiment, the component (B) accounts for 5 to 30% by mass of the composition.
In one embodiment, the component (B) accounts for 10 to 30% by mass of the composition.
In one embodiment, the component (B) accounts for 10 to 20% by mass of the composition.
In one embodiment, the mass ratio of component (B) to component (C) is 10: (0.1-10).
In one embodiment, the mass ratio of component (B) to component (C) is 10: (4-6).
In one embodiment, the mass ratio of the component (B) to the component (D) is (10 to 50000): 1.
in one embodiment, the mass ratio of the component (B) to the component (D) is (10 to 2000): 1.
in one embodiment, the mass ratio of the component (B) to the component (D) is (150 to 2000): 1. the low content of the component (D) results in low sterilization rate and poor antibacterial effect, the high content results in poor spinning stability, and liquid appears at the outlet of the spraying device during electrospinning, which may be caused by the high conductivity of the electrospinning liquid after a certain amount of PHMB is added.
In one embodiment, the composition contains the component (a) other than the components (B), (C) and (D), and the balance is a solvent.
In one embodiment, component (a) comprises 50 to 95% by weight of the composition, including but not limited to 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%.
In one embodiment, the component (a) accounts for 60 to 90% by mass of the composition.
In one embodiment, the component (a) accounts for 70 to 90% by mass of the composition.
In one embodiment, the component (a) accounts for 75 to 85 mass percent of the composition.
In one embodiment, component (C) comprises 1 to 10% by weight of the composition, including but not limited to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%.
In one embodiment, ingredient (D) comprises 0.0001 to 1% by weight of the composition, including, but not limited to, 0.0001%, 0.0002%, 0.0003%, 0.0004%, 0.0005%, 0.0006%, 0.0007%, 0.0008%, 0.0009%, 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%.
In one embodiment, the component (D) accounts for 0.0001 to 0.1% by mass of the composition.
In one embodiment, the composition is used for spray coating an object to be coated to form a fibrous film.
In one embodiment, spraying includes, but is not limited to, electrostatic spraying. In one embodiment, electrostatic spraying can be performed using existing electrostatic spraying devices, including but not limited to portable electrostatic spinning devices.
In one embodiment, the film formation subject includes a skin surface of a human or an animal.
In one embodiment, the composition of the present invention can be sprayed onto a wound site on the skin to form a film having a Young's modulus close to that of the skin, which is beneficial for maintaining a close fit when the wound site is frequently moved.
In one embodiment, the fibrous membrane comprises a medical fibrous membrane. The fiber membrane has antibacterial effect after being sprayed on skin surface of human or animal, and can prevent wound infection and promote wound healing.
According to a second aspect, in an embodiment, there is provided an antimicrobial fibrous membrane produced by the method of any one of the first aspect.
According to a third aspect, in one embodiment, there is provided a composition comprising component (a), component (B), component (C), and component (D);
ingredient (a) comprises a volatile material;
the component (B) contains a hydrophobic polymer having a fiber film-forming ability and being soluble in a volatile substance;
component (C) comprises a surfactant;
ingredient (D) contains an antibacterial agent.
In one embodiment, the volatile material comprises at least one of an alcohol, water, an acid.
In one embodiment, the volatile material comprises at least one of ethanol, isopropanol, butanol, hexafluoroisopropanol, acetic acid, water.
In an embodiment, the hydrophobic polymer comprises at least one of polyvinyl butyral (PVB), polycaprolactone (PCL), polylactic acid (PLA), polylactic-co-glycolic acid (PLGA), polyamide, polyurethane (PU), zein (Zein), polytetrafluoroethylene, polyvinylidene fluoride, polypropylene, polyacrylate, polyethylene terephthalate, silicone rubber.
In one embodiment, the surfactant comprises a polyether surfactant.
In one embodiment, the polyether surfactant includes, but is not limited to, at least one of poloxamer, alcohol polymers:
in one embodiment, the poloxamer may have a molecular weight of 500-20000 Da, including but not limited to 500Da, 600Da, 700Da, 800Da, 900Da, 1000Da, 2000Da, 3000Da, 4000Da, 5000Da, 6000Da, 7000Da, 8000Da, 9000Da, 10000Da, 11000Da, 12000Da, 13000Da, 14000Da, 15000Da, 16000Da, 17000Da, 18000Da, 19000Da, 20000Da. The molecular weight of the poloxamer is not limited, and poloxamers of any molecular weight are suitable for use in the present invention.
In one embodiment, the poloxamer includes, but is not limited to, at least one of poloxamer 101, poloxamer 181, poloxamer 124, poloxamer 188, poloxamer 407, and the like.
In one embodiment, the molecular weight of the alcohol polymer is less than or equal to 2000Da.
In one embodiment, the alcohol polymer includes, but is not limited to, at least one of polyethylene glycol (PEG), polypropylene glycol (PPG), polytetramethylene glycol (PTMG), poly (1,2-butanediol) (PBG).
In one embodiment, the antimicrobial agent comprises at least one of a low-irritation antimicrobial agent and a high-irritation antimicrobial agent.
In one embodiment, the low irritation antimicrobial agent includes, but is not limited to, a guanidine polymer.
In one embodiment, the guanidine polymers include, but are not limited to, biguanide polycationic antimicrobial agents.
In one embodiment, the guanidine polymers include, but are not limited to, at least one of polyhexamethylene guanidine (PHMG), polyhexamethylene biguanide (PH MB), polyaminopropyl biguanide (PAPB), and the like. The various polymers may be mixed as desired to form a mixture as a component in the preparation of the electrospinning solution. The type and the proportion of the antibacterial agent are not limited and can be adjusted according to actual requirements.
In one embodiment, the highly irritating antimicrobial agent includes, but is not limited to, at least one of quaternary ammonium salts, polyquaternary ammonium salts, cationic antimicrobial agents, and polycationic antimicrobial agents. Cations include, but are not limited to, silver ions. The antibacterial agent can be a highly irritant antibacterial agent and can be used in scenes with low irritation requirements.
In one embodiment, ingredient (B) comprises 5 to 50% by weight of the composition, including but not limited to 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, and the like.
In one embodiment, the mass ratio of component (B) to component (C) is 10: (0.1-10).
In one embodiment, the mass ratio of component (B) to component (C) is 10: (4-6).
In one embodiment, the mass ratio of component (B) to component (D) is (10 to 50000): 1.
in one embodiment, the mass ratio of component (B) to component (D) is (10 to 2000): 1.
in one embodiment, the mass ratio of the component (B) to the component (D) is (150 to 2000): 1.
in one embodiment, the composition is used for spray coating an object to be coated to form a fibrous film.
In one embodiment, spraying includes, but is not limited to, electrostatic spraying. In one embodiment, electrostatic spraying can be performed using existing electrostatic spraying devices, including but not limited to portable electrostatic spinning devices.
In one embodiment, the object to be covered with a film includes a skin surface of a human or an animal.
In one embodiment, the composition of the present invention can be sprayed onto a wound site on the skin to form a film having a Young's modulus close to that of the skin, which is beneficial for maintaining a close fit when the wound site is frequently moved.
In one embodiment, the fibrous membrane comprises a medical fibrous membrane. The fiber membrane has antibacterial effect after being sprayed on skin surface of human or animal, and can prevent wound infection and promote wound healing.
In one embodiment, the invention provides that high-efficiency and low-toxicity antibacterial agents such as polyguanidine cationic polymers are added as antibacterial components on the basis of meeting the requirements of the adhesiveness, the mechanical property and the like of the in-situ electrospun membrane. The method has the advantages of simple operation, no irritation, low side effect, wide application range, and wide application prospect in the fields of wound antibiosis and healing promotion.
Conventional hydrophobic fiber membranes tend to release the loaded antimicrobial agent at a rate that is less than ideal and in a desired amount over a desired period of time. In one embodiment, the electrospun membrane of the present invention can release the desired amount of antimicrobial agent in a desired time period, resulting in good antimicrobial action.
In one embodiment, the method provided by the invention comprises spraying the composition to the surface of the skin wound in situ through a portable electrostatic spinning device, so as to form the nanofiber membrane with the functions of controllably releasing the antibacterial agent and promoting the wound healing.
In one embodiment, the dope composition comprises ingredients A, B, C and D. A is solvent selected from 1 or more than 2 volatile substances such as alcohol, water and acid. B is selected from hydrophobic polymers having fiber film forming ability. C is selected from polyether surfactant, and the main function of the component is to improve the spinning stability and the tensile toughness of the fiber film. D is selected from biguanide polycation antibacterial agents. Wherein the mass fraction of B in the spinning solution composition is 5-50%, the mass ratio of B to C is 10:10 to 10:0.1, the mass ratio of B to D is 10:1 to 2000:1.
in one embodiment, the mass fraction of B in the spinning solution composition may be 5 to 50%.
In one embodiment, B comprises, but is not limited to, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50% by mass of the dope composition.
In one embodiment, the solvent a is at least one of ethanol, isopropanol, butanol, hexafluoroisopropanol, acetic acid, and water.
In one embodiment, the hydrophobic polymer B having a fiber forming ability is at least one of polyvinyl butyral (PVB), polycaprolactone (PCL), polylactic acid (PLA), polylactic-co-glycolic acid (PLGA), polyamide, polyurethane (PU), zein (Zein), polytetrafluoroethylene, polyvinylidene fluoride, polypropylene, polyacrylate, polyethylene terephthalate, silicone rubber.
In one embodiment, C is a polyether surfactant including, but not limited to, at least one of the following compounds: poloxamer (poloxamer) with molecular weight of 10000-20000, polyethylene glycol (PEG) with molecular weight less than or equal to 2000, polypropylene glycol (PPG), polytetramethylene glycol (PTMG), and poly (1,2-butanediol) (PBG).
In one embodiment, D is a guanidine polymer, including but not limited to at least one of polyhexamethylene guanidine (PHMG), polyhexamethylene biguanide (PHMB), polyaminopropyl biguanide (PAPB), and the like.
In one embodiment, the composition is sprayed onto the surface of a skin wound by a portable electrospinning device, resulting in a nanofiber membrane that is capable of completely covering the wound.
In one embodiment, compared with the existing antibacterial in-situ electrospinning film forming technology, the electrospinning film prepared by the invention has very good skin adhesion, mechanical properties and the like, and in addition, the low-toxicity and high-efficiency antibacterial agent such as a polyguanidine cationic polymer is added as an antibacterial component, so that the antibacterial agent has no irritation and low side effect, and has high-efficiency antibacterial and wound healing promoting effects.
Examples 1 to 22 and comparative examples 1 to 3
After the formulations of the examples were prepared according to the ratios in table 1, referring to fig. 1, the nanofiber membranes were sprayed on the skin surface of human body using a portable electrospinning device, and then the nanofiber membranes of the respective formulations were subjected to sensory evaluation performance scoring, and at the same time, physical and chemical performance tests were performed, and the scores were performed.
Different compositions were electrospun in situ on the skin, and the resulting nanofiber films were evaluated for spinning stability, sensory properties such as skin-fit and clarity, and tensile properties.
The electrostatic spraying method of each example and the comparative example was as follows:
determining technical parameters of spraying the nanofiber membrane on the portable electrospinning device, specifically, adding the prepared spinning solution into the electrospinning device, selecting a needle with the specification of 23G, turning on a switch, adjusting the voltage to 10kV, the room temperature to 25 ℃, and the relative humidity to 45-65%, so that the distance between a wound and a spray opening is 10-15 cm, and directly spraying the wound on an affected part to form the repair-promoting electrospun fiber membrane.
The purchase sources of each reagent are described below:
PVB: japan waterlogging chemistry, model BM-1.
PEG-8: guangzhou Hui Biotech, inc.
Poloxamer 101: shanghai Aladdin Biotechnology Ltd.
PHMB and PAPB: macro specialization (Guangzhou) Inc.
PU (polyurethane): three liter trade company, PU-3335 (imported from Netherlands) in the area of Changshan, shunddistrict.
The spinning stability evaluation experiment was as follows:
the liquid composition was evaluated for its sprayability using an electrostatic spray device, and the spinning stability was determined as follows:
1 minute: the fibers fly and become fluffy during spinning, the spinning is discontinuous, and a coating film is difficult to form.
And 2, dividing: the fibers fly during spinning, and a coating film can be formed with little force.
And 3, dividing: the spinning is stable, and the formation of the coating is good.
The skin adherence evaluation experiment was as follows:
the films formed in the examples were evaluated for their close adhesion to the skin. The close adhesion was evaluated by touching the film with a finger from a direction perpendicular to the skin, applying a fine vibration load, applying a shear force to the film in a direction parallel to the skin while reciprocating with the finger, and visually observing the state of the film thereafter, and the skin adhesion was given according to the following rules:
1 minute: when a minute vibration load is applied in the vertical direction with a finger, the coating film is almost completely peeled off.
And 2, dividing: when a minute vibration load is applied in the vertical direction with a finger, the fibers forming the coating are partially peeled off.
And 3, dividing: although peeling did not occur in the perpendicular direction, almost all of the coating peeled off when a shear force was applied in the parallel direction.
And 4, dividing: although peeling does not occur in the perpendicular direction, a part of the coating or the fiber is peeled off when a shear force is applied in the parallel direction with a finger.
And 5, dividing: peeling does not occur in the perpendicular direction, and peeling does not occur in the coating film or the fiber even when a shear force is applied in the parallel direction.
The maximum tensile force evaluation test is as follows:
the formed coating was tested for tensile breaking force (i.e., maximum tensile force) using a tensile testing machine (model MY-DL-20, minty instruments ltd., shenzhen) to evaluate tensile properties, the coating specification was 2 × 4cm, and the thickness was 50 μm.
The assignment rule of the maximum stretching force is as follows:
1 minute: the maximum tensile force is more than or equal to 0N and less than 0.8N.
And 2, dividing: the maximum stretching force is more than or equal to 0.8N and less than or equal to 1.2N.
And 3, dividing: the maximum tensile force is more than 1.2N.
The tensile toughness evaluation test is as follows:
the tensile deformation rate is measured by a tensile testing machine, the tensile toughness is evaluated through the tensile deformation rate, and the assigning rule of the tensile toughness is as follows:
1 minute: the tensile deformation rate is less than 80 percent.
And 2, dividing: the tensile deformation rate is more than or equal to 80 percent and less than or equal to 160 percent.
And 3, dividing: the tensile deformation rate is more than 160 percent.
The results of the tests and scoring are shown in table 1.
TABLE 1 electrospinning liquid formulation
Figure BDA0003845821150000081
Figure BDA0003845821150000091
Different components were dissolved together in ethanol in the amounts shown in table 1 to prepare electrospinning solutions. The composition is sprayed on the surface of aluminum foil or wound by a portable electrospinning device to obtain the nanofiber membrane which is uniform in thickness and can completely cover the surface. The fiber diameter of the nanofiber membrane was determined by scanning electron microscopy.
Fig. 2 is a scanning electron micrograph of the PVB + polyether + poly biguanide PHMB nanofiber film prepared in example 10, showing that the nanofiber diameter of the electrospun film prepared in example 11 is 4.0 ± 0.8 μm.
The electron micrographs of the fibrous membranes produced in the other examples are similar to those of FIG. 2.
As can be seen from the performance evaluation results in table 1, examples 1 to 10 all have better spinning stability, skin-attachment property, tensile strength and tensile toughness, and in example 11, the spinning stability is affected and reduced to a certain extent due to the addition of the antibacterial agent increased based on example 10, and the liquid ejection phenomenon occurs during electrospinning, which may be caused by the excessively high conductivity of the electrospinning liquid after a certain amount of PHMB is added to the electrospinning liquid.
In comparative examples 2 and 3, the skin-fit property and tensile toughness were reduced to some extent because component C was not added.
The amounts of PAPB added in examples 12-19 were similar to those in examples 1,2, 5-10, and thus all had better spinning stability, skin-adhesion, tensile strength, and tensile toughness.
In examples 20 to 22, PHMB was added in an amount of 0.1% to the PU and polyether electrospinning solutions, and the spinning stability, skin-adhesion, tensile strength and tensile toughness were also excellent.
Test example 1
The test example tests the release rate of PAPB in different PAPB loaded fibrous membranes. The artificial sweat simulating the human skin sweat is configured, and the method comprises the following steps: mixing sodium chloride, urea and lactic acid according to a mass ratio of 5:1:1 dissolved in ultrapure water, total mass concentration of the materials0.7% and then with NH 4 OH adjusts the pH to 6.6. The release rate of PAPB from three drug-loaded fibrous membranes, PVB + PAPB (comparative example 3), PVB + PEG8+ PAPB (example 12) and PVB + P101+ PAPB (example 13), was then determined at 32 ℃ in the artificial sweat and PAPB concentrations were determined at 1, 3, 6, 12, 24 and 72h samples, respectively. The concentration of PAPB is quantitatively determined by UPLC (Ultra Performance Liquid Chromatography), and the specific method comprises the following steps: the detection wavelength is 236nm, and the mobile phase is methanol: 0.02mol/L ammonium formate =40 (volume ratio), flow rate 0.3mL/min, injection volume 10 μ L. Cutting the PAPB-loaded electro-spinning membrane into a certain mass size, cutting into two parts, dissolving one part with 1mL of ethanol, adding 4mL of artificial sweat, performing vortex oscillation for 5min to obtain a suspension, and performing UPLC detection by using a filter membrane. And cutting the other part of the electrospun membrane into a piece, soaking the piece in 5mL of artificial sweat, oscillating at certain time interval, sucking 200 mu L of sample injection, and simultaneously supplementing 200 mu L of artificial sweat into the soak solution. The amount of PAPB released (B) and the initial amount of PAPB (A) were calculated from the standard curve. The percentage of PAPB released was calculated as follows:
Figure BDA0003845821150000101
as shown in fig. 3, the results show that the PAPB release rates of the three fiber membranes at the initial 1 hour are 9.9%, 22.8% and 17.9%, respectively, which indicates that the addition of both polyether PEG8 and P101 can significantly increase the release rate of PA PB compared to the pure PVB antibacterial electrospun membrane. It can be seen that the polyether-containing fiber membrane within 12h can continuously increase the release rate of PAPB. The release of PAPB in the three fibrous membranes was gradually close to 72 hours later, and the release rates at 72 hours were 45.6%, 50.6% and 47.6%, respectively. These results indicate that the addition of the polyethers PEG8 and P101 can significantly facilitate the release of PAPB in the fibrous membrane, probably because the polyethers are relatively more hydrophilic and are more easily dissolved out of the fibrous membrane into sweat, thereby facilitating the release of hydrophilic PAPB in sweat.
Test example 2
In the test example, escherichia coli is used for a carrier antibacterial experiment, and the national standard WS/T650-2019 antibacterial and bacteriostatic effect evaluation method is referred to. The specific method comprises the following steps:
preparing electro-spinning ethanol solution with different concentrations of PHMB according to the formula shown in the comparative example 1 and the examples 5-10 in the table 1, spraying a film on equipment, uniformly spraying the film on a receiver for 6min, preparing 2 parts of small round sheets with the diameter of 1cm by a puncher, and sterilizing for later use. Diluting Escherichia coli liquid to 1.0 x 10 with PBS 5 CFU/mL~9.0*10 5 And (3) respectively dripping 20 mu L of escherichia coli culture solution on each small circle per mL of CFU, putting the small circles into a humid environment at 37 ℃ to culture for 0.5h and 24h respectively after the addition, clamping the sample slice into a prepared neutralizer (2.5 mL) by using sterile forceps, and standing for 10min after shaking. And then, vortexing and oscillating the neutralizing agent for 0.5min, washing the bacteria, respectively sucking 100 mu L of sample liquid, determining the number of the surviving bacteria according to a viable bacteria culture method, and performing serial dilution by 10 times and viable bacteria culture counting when the number of growing colonies on a flat plate is large. Wherein No. 0 is used as a positive control, and the diluent, the neutralizer and the culture medium in the same test batch are used as negative controls. The culture dish is cultured for 24h at 37 ℃, colonies are counted, and the average value of the bacterial load is taken in parallel experiments, and then the sterilization rate is calculated according to the following formula.
And (3) calculating the sterilization rate:
Figure BDA0003845821150000102
in the formula:
X-Sterilization Rate,%;
a-recovered bacteria amount of control sample, in CFU/tablet;
b-recovery of bacteria in test specimens in CFU/disc.
The sterilization rate is more than or equal to 90 percent, and the antibacterial effect is judged; the sterilization rate is more than or equal to 99 percent, and the antibacterial effect is stronger.
FIG. 4 shows the results of the antibacterial test of the sprayed films of the electrospun solutions loaded with different PHMB contents. It can be seen that the sterilizing ability of the electrospun membrane gradually improves as the PHMB content increases. When the bacterial liquid is cultured for 0.5h in a membrane-carrying way, only the PHMB electrospinning liquid sprayed membrane with the content of 0.1 percent has stronger antibacterial action, and the other contents have no antibacterial action. Compared with the bacterial liquid membrane-carried culture for 0.5h, the sterilizing effect of the electrospun membrane is remarkably improved after the bacterial liquid membrane-carried culture is carried out for 24h. The PHMB electrospinning solution sprayed film with the contents of 0.1%, 0.03% and 0.01% has an antibacterial effect, and the other contents have no antibacterial effect; the PHMB electrospinning liquid spraying film with the content of 0.1 percent and 0.03 percent has stronger antibacterial action.
In fig. 4, the PHMB concentrations in the electrospinning solution were 0%, 0.0003%, 0.001%, 0.003%, 0.01%, 0.03%, and 0.1% by mass in the order from left to right in each group, divided by time.
Test example 3
In this test example, methicillin-resistant staphylococcus aureus (MRSA) was used to perform the PHMB electrospun membrane-loaded carrier antibacterial experiments of comparative example 1 and examples 5 to 10, and the test method was as in test example 2. The antibacterial result is shown in fig. 5, and similar to the antibacterial test result of escherichia coli, the bactericidal capacity of the electrospun membrane is gradually improved with the increase of the PHMB content. When the bacteria liquid is cultured for 0.5h, only the sprayed film of the PHMB electrospinning liquid with the content of 0.1 percent has stronger antibacterial action, and the other contents have no antibacterial action. After the culture is carried out for 24 hours, the sterilization effect of the electrospun membrane is obviously improved. Wherein the PHMB electrospinning liquid spraying film with the content of 0.1%, 0.03% and 0.01% has antibacterial effect, and the other content has no antibacterial effect; the PHMB electrospinning liquid spraying film with the content of 0.1 percent and 0.03 percent has stronger antibacterial action.
In fig. 5, the PHMB concentrations in the electrospinning solution were 0%, 0.0003%, 0.001%, 0.003%, 0.01%, 0.03%, and 0.1% by mass in the order from left to right in each group, divided by time.
Test example 4
In this test example, the carrier antibacterial test of comparative example 1 and examples 14 to 19, which carries an electrospun membrane of another antibacterial agent PAPB, was carried out using escherichia coli, and the test method was according to test example 2. The antibacterial result is shown in fig. 6, and similar to the antibacterial test result of the PHMB-loaded electrospun membrane, the bactericidal capacity of the electrospun membrane is gradually improved along with the increase of the content of PAPB. When the bacterial liquid is cultured for 0.5h in a membrane-carrying manner, only the PAPB electro-spinning liquid sprayed membrane with the content of 0.1% has a strong antibacterial effect, and the other contents have no antibacterial effect. After the culture is carried out for 24 hours, the sterilization effect of the electrospun membrane is obviously improved. Wherein, the PAPB electro-spinning liquid spraying film with the content of 0.1 percent and 0.03 percent has the antibacterial effect, the content of 0.01 percent is approximate to the antibacterial effect, and the other content has no antibacterial effect; the PAPB electro-spinning liquid with the content of 0.1% has stronger antibacterial action.
In fig. 6, the mass percentage concentrations of PAPBs in the electrospinning solution were 0%, 0.0003%, 0.001%, 0.003%, 0.01%, 0.03%, and 0.1% in order from left to right in each group.
Test example 5
In this test example, methicillin-resistant staphylococcus aureus (MRSA) was used to perform the carrier antibacterial test of the PAPB-loaded electrospun membranes of comparative example 1 and examples 14 to 19, and the test method was referred to test example 2. The antibacterial result is shown in fig. 7, and similar to the antibacterial test result of the PHMB-loaded electrospun membrane, the antibacterial ability of the electrospun membrane is gradually improved with the increase of the PAPB content. When the bacterial liquid is cultured for 0.5h in a membrane-carrying manner, only the PAPB electro-spinning liquid sprayed membrane with the content of 0.1% has a strong antibacterial effect, and the other contents have no antibacterial effect. After the culture is carried out for 24 hours, the sterilization effect of the electrospun membrane is obviously improved. Wherein, the PAPB electro-spinning liquid spraying film with the content of 0.1 percent and 0.03 percent has antibacterial function, and the other content has no antibacterial function; the PAPB electro-spinning liquid with the content of 0.1% has stronger antibacterial action.
In fig. 7, the mass percentage concentrations of PAPBs in the electrospinning solution were 0%, 0.0003%, 0.001%, 0.003%, 0.01%, 0.03%, and 0.1% in order from left to right in each group, grouped by time.
Test example 6
In this test example, the PHMB electrospun membrane-loaded carrier antibacterial experiments of examples 20 to 22 were carried out using escherichia coli and methicillin-resistant staphylococcus aureus (MRSA), according to the test method described in test example 2, and the bacterial solution-loaded membrane was cultured for 24 hours. The antibacterial results are shown in fig. 8, and the sterilization rates of the three examples with the PHMB content of 0.1% are all greater than 99%, which shows that the examples have strong antibacterial effects.
In fig. 8, the strains are grouped into groups, and in each group, from left to right, PU + PEG8+ PHMB, PU + P101+ PHM B, and PU + PEG8+ P101+ PHMB are provided in sequence.
The skin adhesiveness and mechanical property of the existing in-situ electrospun membrane with antibacterial effect are not good and cannot meet the requirements, and in one embodiment, the invention obviously improves the skin adhesiveness and mechanical property of the electrospun membrane.
The antibacterial components used in the prior art have large toxicity and side effects, thereby limiting the antibacterial and healing promoting effects of the electrospun membrane. The existing electrospun membrane uses polyquaternium as an antibacterial material, has irritation to wounds and can burn eyes sometimes. It has been reported that certain polyquaterniums can cause allergic pimples to the skin. These problems limit their antimicrobial and healing efficacy. In one embodiment, the present invention may solve the aforementioned problems, using a low-irritation antibacterial agent, thereby improving the wound-healing effect.
In one embodiment, the invention provides an antibacterial skin in-situ electrostatic spinning nanofiber membrane and a preparation method thereof, in view of the fact that ideal antibacterial and healing promoting effects are difficult to achieve by existing dressing products such as gauze for clinical wound healing.
In one embodiment, the antibacterial agent in the fiber membrane of the present invention may be a low-irritation antibacterial agent or a high-irritation antibacterial agent, and the corresponding type of antibacterial agent may be selected according to different usage scenarios.
The present invention has been described in terms of specific examples, which are provided to aid understanding of the invention and are not intended to be limiting. Numerous simple deductions, modifications or substitutions may also be made by those skilled in the art in light of the present teachings.

Claims (10)

1. A method of making an antimicrobial fibrous membrane comprising:
a spraying step of spraying a composition onto a coating film formation object to form the fiber film;
the composition comprises a component (A), a component (B), a component (C) and a component (D);
the ingredient (a) comprises a volatile material;
the component (B) comprises a hydrophobic polymer having a fibrous film-forming ability and being soluble in the volatile substance;
the component (C) comprises a surfactant;
the component (D) contains an antibacterial agent.
2. The method of claim 1, wherein the volatile material comprises at least one of an alcohol, water, an acid;
preferably, the hydrophobic polymer comprises at least one of polyvinyl butyral, polycaprolactone, polylactic acid, polylactic-co-glycolic acid, polyamide, polyurethane, zein, polytetrafluoroethylene, polyvinylidene fluoride, polypropylene, polyacrylate, polyethylene terephthalate, silicone rubber;
preferably, the surfactant comprises a polyether surfactant.
3. The method of claim 1, wherein the volatile material comprises at least one of ethanol, isopropanol, butanol, hexafluoroisopropanol, acetic acid, water;
preferably, the polyether surfactant comprises at least one of poloxamer and alcohol polymer;
preferably, the molecular weight of the alcohol polymer is less than or equal to 2000Da;
preferably, the poloxamer comprises at least one of poloxamer 101, poloxamer 181, poloxamer 124, poloxamer 188, poloxamer 407;
preferably, the alcohol polymer comprises at least one of polyethylene glycol, polypropylene glycol, polybutylene glycol, poly (1,2-butanediol);
preferably, the polyethylene glycol comprises PEG-8.
4. The method of claim 1, wherein the antimicrobial agent comprises at least one of a low-irritation antimicrobial agent and a high-irritation antimicrobial agent.
5. The method of claim 4, wherein the low-irritation antimicrobial agent comprises a guanidine polymer;
preferably, the guanidine polymer comprises a biguanide polycationic antibacterial agent;
preferably, the guanidine polymer comprises at least one of polyhexamethylene guanidine, polyhexamethylene biguanide, polyaminopropyl biguanide;
preferably, the highly irritating antibacterial agent comprises at least one of quaternary ammonium salt, polyquaternary ammonium salt, cationic antibacterial agent, polycationic antibacterial agent.
6. The method of claim 1, wherein the component (B) comprises 5 to 50% by weight of the composition;
preferably, the mass ratio of the component (B) to the component (C) is 10: (0.1 to 10);
preferably, the mass ratio of the component (B) to the component (D) is (10 to 50000): 1;
preferably, the mass ratio of the component (B) to the component (C) is 10: (4-6);
preferably, the mass ratio of the component (B) to the component (D) is (10 to 2000): 1;
preferably, the mass ratio of the component (B) to the component (D) is (150 to 2000): 1;
preferably, the spraying comprises electrostatic spraying;
preferably, the film formation object includes a skin surface of a human or an animal.
7. An antibacterial fibrous membrane produced by the method of any one of claims 1 to 6.
8. A composition comprising a component (A), a component (B), a component (C) and a component (D);
the ingredient (a) comprises a volatile material;
the component (B) comprises a hydrophobic polymer having a fiber film-forming ability and being soluble in the volatile substance;
the component (C) comprises a surfactant;
the component (D) contains an antibacterial agent.
9. The composition of claim 8, wherein the volatile material comprises at least one of an alcohol, water, an acid;
preferably, the hydrophobic polymer comprises at least one of polyvinyl butyral, polycaprolactone, polylactic acid, polylactic-co-glycolic acid, polyamide, polyurethane, zein, polytetrafluoroethylene, polyvinylidene fluoride, polypropylene, polyacrylate, polyethylene terephthalate, silicone rubber;
preferably, the surfactant comprises a polyether surfactant;
preferably, the polyether surfactant comprises at least one of poloxamer and alcohol polymer;
preferably, the antibacterial agent comprises at least one of a low irritative antibacterial agent, a high irritative antibacterial agent;
preferably, the low-irritation antimicrobial agent comprises a guanidine polymer;
preferably, the guanidine polymer comprises a biguanide polycationic antibacterial agent;
preferably, the guanidine-based polymer comprises at least one of polyhexamethylene guanidine, polyhexamethylene biguanide, polyaminopropyl biguanide;
preferably, the highly irritating antibacterial agent comprises at least one of quaternary ammonium salt, polyquaternary ammonium salt, cationic antibacterial agent, polycationic antibacterial agent.
10. The composition according to claim 8, wherein the component (B) accounts for 5 to 50% by mass of the composition;
preferably, the mass ratio of the component (B) to the component (C) is 10: (0.1 to 10);
preferably, the mass ratio of the component (B) to the component (D) is (10 to 50000): 1;
preferably, the mass ratio of the component (B) to the component (C) is 10: (4-6);
preferably, the mass ratio of the component (B) to the component (D) is (10 to 2000): 1;
preferably, the mass ratio of the component (B) to the component (D) is (150 to 2000): 1;
preferably, the composition is used for spraying a coating film formation object to form a fiber film;
preferably, the spraying comprises electrostatic spraying;
preferably, the film formation object includes a skin surface of a human or an animal.
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