Method for manufacturing medical nanofibers and medical nanofibers manufactured thereby

Abstract

This invention relates to a method for manufacturing medical nanofibers, comprising the following steps: (a) mixing polyethylene oxide with water; (b) adding at least one of hyaluronic acid, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginate, carrageenan, chitin, chitosan, poloxamer, cellulose, or carboxymethyl chitosan and menthol to 100 parts by weight of the mixed solution of step (a) and mixing; (c) adding ethanol to the mixed solution of step (b) and mixing; and (d) electrospinning the spinning solution of step (c).

Description

Technical Field

[0001] This invention relates to a method for manufacturing medical nanofibers and the medical nanofibers thus manufactured, and more specifically, to the manufacture of medical nanofibers using water-soluble polymers that utilize highly absorbent static electricity, characterized by improved cooling function and skin adhesion within the nanofibers. Background Technology

[0002] In recent years, with the rapid development of an aging society and the increase in metabolic diseases, the number of patients with chronic wounds has been increasing, thus the treatment of chronic wounds has received much attention. Chronic wounds refer to wounds that have not healed after a certain period of time following the normal wound healing process. This time is usually 4 weeks to more than 3 months, and refers to unhealed wounds where the healed area is still less than 20% to 30% even with routine wound care and treatment.

[0003] Unlike general wound treatments, products for treating chronic wounds are categorized into various types of dressings based on the amount of exudate. In recent years, antibacterial dressings, analgesic functional dressings, and cell therapy agents that promote wound healing have been developed and applied to refractory chronic wounds. Furthermore, wound treatments can be classified according to their raw materials, such as film-type, foam-type, hydrogel-type, and hydrocolloid-type, and their raw materials are increasingly diversified, including the use of bio-derived materials. To promote rapid wound healing, these wound treatments need to effectively absorb exudate, prevent the wound site from being exposed to the outside, and maintain a moist state, thereby promoting epithelial cell regeneration more effectively than the scab formation healing process.

[0004] Therefore, in recent years, in order to overcome the problems of biodegradable synthetic polymers, there has been an increasing number of instances using bio-derived polymers.

[0005] As a representative bio-derived polymer, hyaluronic acid is a naturally synthesized substance that is widely found in animal skin. Due to its excellent biocompatibility and biodegradability, it is widely used as a scaffold material for tissue culture.

[0006] Hyaluronic acid is hydrophilic due to the presence of a large number of hydroxyl groups (OH) in its molecules, and because the polymer itself carries a positive charge, it is difficult to use hyaluronic acid alone for electrospinning. Therefore, there are no reports to date on the manufacture of nanofibers by electrospinning.

[0007] Therefore, by using triboelectric electrostatics to nanospin a solution containing hyaluronic acid, medical nanofibers with good absorbency, adhesion, and antibacterial properties can be manufactured. Summary of the Invention

[0008] Technical challenges to be addressed The purpose of this invention is to provide a medical nanofiber manufactured by electrostatic means using a portable nanofiber manufacturing device based on triboelectric static electricity. This nanofiber can maintain a moist environment between the wound and the dressing preparation, has appropriate absorbency and permeability, prevents the wound surface from drying out and prevents maceration of the surrounding normal skin, while also enabling gas exchange, preventing the invasion of external bacteria, and adhering to the wound surface during replacement, thus causing less damage to newly formed tissues.

[0009] Problem-solving methods To address the aforementioned problems, one aspect of the present invention provides a method for manufacturing medical nanofibers, comprising the following steps: (a) mixing polyethylene oxide with water; (b) adding at least one of hyaluronic acid, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginate, carrageenan, chitin, chitosan, poloxamer, cellulose, or carboxymethyl chitosan, and menthol to 100 parts by weight of the mixed solution from step (a) and mixing therewith; (c) adding ethanol to the mixed solution from step (b) and mixing therewith; and (d) electrospinning the spinning solution from step (c).

[0010] Furthermore, another aspect of the present invention provides a method for manufacturing medical nanofibers, characterized in that the polyethylene oxide comprises at least one of hyaluronic acid, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginate, carrageenan, chitin, chitosan, poloxamer, cellulose, or carboxymethyl chitosan; and the weight ratio of the mixture of water and ethanol is 3-10 : 0.5-5 : 75-85, wherein the weight ratio of ethanol to water is 9:1-2:1.

[0011] Furthermore, another aspect of the present invention provides a biodegradable medical nanofiber manufactured according to the above method, having a diameter of 10 to 1000 nm.

[0012] Invention Effects The medical nanofibers of this invention have excellent skin adhesion and absorption capacity, and can reduce the heat sensation of wounds and block bacterial infection.

[0013] Furthermore, the present invention aims to provide a burn treatment agent that requires rapid bandaging in burn wound management and can be used continuously during wound treatment.

[0014] In addition, the present invention has the effect of preventing external infection and has excellent exudate absorption capacity. Attached Figure Description

[0015] Figure 1 This is a conceptual diagram illustrating the portable nanofiber manufacturing apparatus based on triboelectricity for use in nanospinning form according to the present invention.

[0016] Figure 2 , Figure 3 This is an enlarged photograph of an embodiment of the medical nanofiber of the present invention. Detailed Implementation

[0017] The preferred embodiments of the present invention will now be described in detail. First, in describing the present invention, to avoid obscuring the main points of the invention, specific descriptions of relevant well-known functions or structures will be omitted.

[0018] The terms "about," "basically," etc., used in this specification to indicate degree, when they have inherent manufacturing and material tolerances in their meaning, are used to indicate the value or close to the value, and are used to prevent unlawful infringers from improperly using the disclosure of precise or absolute values ​​mentioned to help understand the present invention.

[0019] This invention relates to a method for manufacturing medical nanofibers, comprising the following steps: (a) the step of mixing polyethylene oxide with water; (b) the step of adding at least one of hyaluronic acid, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginate, carrageenan, chitin, chitosan, poloxamer, cellulose or carboxymethyl chitosan and menthol to 100 parts by weight of the mixed solution of step (a) and mixing; (c) the step of adding ethanol to the mixed solution of step (b) and mixing; and (d) the step of electrospinning the spinning solution of step (c).

[0020] At this point, regarding the content of the composition, it is appropriate that at least one component selected from hyaluronic acid, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginate, carrageenan, chitin, chitosan, poloxamer, cellulose, or carboxymethyl chitosan; and the weight ratio of the water to ethanol mixture is 3–10 : 0.5–5 : 75–85, and the weight ratio of ethanol to water is 9:1–2:1.

[0021] Polyethylene oxide (PEO) is a linear crystalline polymer with ether groups. Due to the presence of ethylene oxide in the repeating units, it has excellent hydrophilicity and solubility. It is used as a polymer electrolyte in lithium batteries not only because of its high viscosity, but also because it is soluble in a variety of organic solvents except water. It has high gelation ability and low toxicity and does not spoil over a long period of time. Therefore, it can also be widely used as a functional additive in pharmaceuticals, cosmetics, food processing, textiles and other fields, such as a nonionic emulsifier, and as a drug delivery carrier or component of block copolymers in biodegradable drug delivery systems.

[0022] The hyaluronic acid of this invention is derived from Streptococcus vesicanthii (Streptococcus Streptococcus zooepidemicusThe hyaluronic acid is extracted from [a specific source] and has a weight-average molecular weight of 100,000 to 1,600,000 Daltons (Da), more preferably 156,000 to 1,590,000 Daltons (Da). Furthermore, to improve solubility, hyaluronic acid with terminal groups replaced by Na is used. In this case, if the weight-average molecular weight of the hyaluronic acid is less than 100,000 Daltons (Da), hydrolysis is too rapid, resulting in decreased stability of the final manufactured sheet; if it exceeds 1,600,000 Daltons (Da), the yield of nanofibers decreases, which is therefore undesirable.

[0023] Polyvinyl alcohol (PVA) is also a linear crystalline polymer with hydroxyl groups. It is insoluble in organic solvents, thus exhibiting excellent solvent resistance. Furthermore, it possesses surface-active properties, excellent emulsifying / dispersing power, and does not spoil, decompose, or depolymerize, making it physiologically harmless. Therefore, due to its excellent solvent resistance, alkali resistance, and adhesive properties, PVA is widely used in pharmaceuticals, cosmetics, and food industries. Examples include hydrogels for human organ replacement, drug delivery systems, bioreactors, and biosensors. It is also widely used in materials such as anti-cracking cardboard, plywood, office adhesives, anti-wrinkle sizing agents for fibers, thickeners for color printing, and emulsifiers for emulsion polymerization or suspension polymerization.

[0024] In addition, polyvinylpyrrolidone (PVP), alginate, carrageenan, or carboxymethyl chitosan are polymers that can be added to electrospinning, with the molecular weight of the water-soluble polymer controlled in the range of Mv 100,000 to 1,000,000.

[0025] Various substances, including flavoring agents such as menthol and / or other additives, may be added here. Suitable flavoring agents include menthol, eugenol, spearmint, peppermint, cocoa, vanilla, cinnamon, licorice, citrus, or other fruit flavors and combinations thereof. Examples of non-flavoring additives include coolants, diluents, aerosol forming agents, and equivalents.

[0026] The features and other advantages of the present invention described above will become more apparent from the embodiments described below.

[0027] The following embodiments are described for illustrative purposes only and should not be construed as limiting or restricting the scope of protection of the present invention.

[0028] [Example 1] 1. Weigh 3 mg of polyethylene oxide (PEO) using a precision balance.

[0029] 2. Place the Falcon tube on a precision balance, zero it, and add water to 18.75 mg.

[0030] 3. Slowly add powder No. 1 to solution No. 2 while stirring.

[0031] 4. Add 4 mg of hyaluronic acid and 1 mg of menthol to solution 3.

[0032] 5. Stir solution No. 4 at 60°C for 1 hour to ensure it is fully dissolved.

[0033] 6. While stirring solution 5 in a stirrer, slowly add 56.25 mg of alcohol (ethanol) (density: 0.79 g / mL).

[0034] 7. Stir solution No. 6 at 60°C for 1 hour using a stirrer.

[0035] 8. Inject solution No. 7 into a syringe at a rate of 1 cc to prepare a nanofiber solution.

[0036] 9. Electrospin the prepared nanofiber solution. (*Electrospinning can be performed using the portable triboelectric device described in Korean Patent No. 102353832, see [link to patent details]). Figure 1 ) [Examples 2-12], [Comparative Examples 1-3] Except for the different component contents in Tables 1 to 3 below, the manufacturing method is the same as in Example 1.

[0037] [Physical Property Experiment] pass Figure 2 , 3 SEM was used to confirm whether nanofibers were manufactured, their diameter, nanofiber pores, and morphology.

[0038] 1. Absorption Rate (%): Nanofibers with a thickness of 1.0 mm were fabricated using a triboelectric generator and cut into 5×5 cm pieces. The absorption rate was then measured. The initial weight of the glass culture dish was determined. After cutting the sample into 5×5 cm pieces, the weight was weighed (a). Then, 10 g, 20 g, 30 g, and 40 g of distilled water were added to the sample. After placing the samples in a 37℃ incubator for 24 hours, the nanofiber samples were carefully suspended with tweezers for 30 seconds and then weighed. Absorption Rate (%) = (W2-W1) / W1 × 100 2. Adhesion force determination: A 1 mm thick nanofiber was fabricated on a stainless steel plate (50 × 125 mm), and then a 10 mm thick nanofiber was carefully separated from one end of the stainless steel plate. The sample was fixed to the stainless steel plate at 180° on a universal testing machine, and a tensile test was performed at a speed of 5 mm / s to determine the load.

[0039] 3. Bacterial Barrier Test: The test shall be conducted in accordance with the provisions of EN 137265 regarding bacterial barrier performance, bacterial characteristics and conditions under humid conditions. 10×10 cm nanofibers shall be fabricated and cut into 5×5 cm samples for testing.

[0040] 1) To obtain approximately 10 9 Cell count / ml, cultured Serratia marcescens in nutrient broth (nutrient liquid culture medium) at 20-25°C. Serratia marcescens (Serratia marcescens culture ATCC 8100) 24 hours.

[0041] 2) Under aseptic conditions, transfer a sterile dressing sample of at least 5 cm × 5 cm to a petri dish filled with a sterile nutrient agar medium substrate.

[0042] 3) Divide the culture medium into 5 equal parts using a sterile pipette and place them at the four edges and the center.

[0043] 4) Incubate the culture plate at 20-25℃ for 24 hours.

[0044] 5) After incubation, remove the liquid culture medium from the dressing with a sterile pipette and remove the dressing from the agar surface with sterile forceps.

[0045] 6) Incubate at 20-25℃ for another 24 hours.

[0046] 7) Check the surface covered by the sample in the culture plate for the presence of Serratia marcescens.

[0047] *Note: Serratia marcescens exhibits distinct red growth on the agar surface.

[0048] Table 1

[0049] As shown in Table 1, Comparative Example 2 did not contain polyethylene oxide, while Comparative Example 1 had a polyethylene oxide weight ratio of water to ethanol that exceeded the range of 3-10: 75-85. Comparative Example 1 showed agglomeration of nanofibers, while Comparative Example 2 could not be spun.

[0050] Table 2

[0051] As shown in Table 2, Comparative Examples 3 and 4 are cases where the weight ratio of ethanol to water exceeds 9:1 to 2:1. In Comparative Example 3, the weight ratio of ethanol to water is 10:1, and in Comparative Example 4 it is 1:1. Comparative Example 3 did not produce a bacterial barrier, and Comparative Example 4 could not produce nanofibers.

[0052] Table 3

[0053] Referring to Table 3, Comparative Examples 5 and 6 are cases where the content of hyaluronic acid alone deviates from the weight ratio of 0.5 to 5 in at least one of the components of hyaluronic acid, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginate, carrageenan, or carboxymethyl chitosan. The adhesion and absorption rate of Comparative Example 5 are lower than those of the Examples, and it is difficult to manufacture nanofibers in Comparative Example 6.

[0054] The present invention described above is not limited to the above embodiments and drawings. Those skilled in the art to which this invention pertains should understand that various substitutions, modifications and alterations can be made without departing from the technical concept of this invention.

Claims

1. A method for manufacturing medical nanofibers, comprising the following steps: (a) The step of mixing polyethylene oxide with water; (b) The step of adding at least one of hyaluronic acid, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginate, carrageenan, chitin, chitosan, poloxamer, cellulose or carboxymethyl chitosan and menthol to 100 parts by weight of the mixed solution of step (a) and mixing them together. (c) The step of adding ethanol to the mixed solution of step (b) and mixing; as well as (d) Electrospinning the spinning solution from step (c).

2. The method for manufacturing medical nanofibers according to claim 1, characterized in that, The polyoxyethylene; At least one component selected from hyaluronic acid, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginate, carrageenan, chitin, chitosan, poloxamer, cellulose, or carboxymethyl chitosan; and The weight ratio of the water to ethanol mixture is: 3～10 : 0.5～5 : 75～85， The weight ratio of ethanol to water is 9:1 to 2:

1.

3. A biodegradable medical nanofiber, manufactured according to the method of claim 1 or 2, Its diameter is 10–1000 nm.

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