Medical Nanofiber Manufacturing Method and Medical Nanofibers Derived From It

Abstract

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

Description

Technology Field

[0001] The present invention relates to a method for manufacturing medical nanofibers and medical nanofibers produced thereby. More specifically, the invention relates to manufacturing medical nanofibers utilizing highly absorbent static electricity using a water-soluble polymer, characterized by improved cooling function and skin adhesion within the nanofibers. Background Technology

[0003] Recently, due to the rapid growth of the aging society and the increase in metabolic diseases, the number of patients with chronic wounds is increasing, leading to a focus on the treatment of chronic wounds. A chronic wound refers to a wound that does not heal even after a certain period has elapsed following the normal wound healing process; this period generally ranges from 4 weeks to 3 months or more, and it refers to a wound that does not heal in less than 20-30% of cases even with normal wound care and treatment.

[0004] Unlike general wound treatments, therapeutic products for chronic wounds include various types of dressings depending on the amount of exudate. Recently, antibacterial dressings, functional dressings that alleviate pain, and cell therapies that promote wound healing have been developed and are being used for intractable chronic wounds. Furthermore, wound treatments are classified into film, foam, hydrogel, and hydrocolloid types based on their raw materials, and there is a recent trend toward significant diversification of raw materials, including the use of bio-derived materials. For rapid wound healing, effectively absorbing exudate, preventing the wound site from being exposed to the outside, and maintaining a moist environment promotes the regeneration of epithelial cells more effectively than the healing process of forming a scab.

[0005] Accordingly, recently, there has been an increasing number of instances using bio-derived polymers to overcome the problems of biodegradable synthetic polymers.

[0006] As a representative bio-derived polymer, hyaluronic acid is a naturally synthesized substance abundant in animal skin. Due to its excellent biocompatibility and biodegradability, it is a natural polymer widely used as a scaffold material for tissue culture.

[0007] Hyaluronic acid is hydrophilic due to the large number of hydroxyl groups (-OH) within its molecule and the positive charge of the polymer itself, which limits electrospinning with hyaluronic acid as a single material, and consequently, there have been no reports on the production of nanofibers by the electrospinning method.

[0008] Accordingly, medical nanofibers with excellent absorption, adhesion, and antibacterial properties were manufactured by nanospinning using static electricity, a triboelectricity, with a solution containing hyaluronic acid. Prior art literature

[0010] (00001) Korean Registered Patent No. 10-1224882 (Publication Date 2013.01.22) Nanofiber sheet composed of hyaluronic acid and nanofiber support for tissue culture using the same (00002) Korean Registered Patent No. 10-2353832 (Publication Date 2022.01.21) Portable nanofiber manufacturing device based on tribostatic electrostatics The problem to be solved

[0011] The objective of the present invention is to provide medical nanofibers using electrostatics that maintain a moist environment between the wound and the dressing, have appropriate absorbency and moisture permeability, prevent drying of the wound surface and prevention of maceration of surrounding normal skin, as well as gas exchange, prevent bacterial invasion from the outside, and adhere to the wound surface during exchange, thereby causing low damage to new tissues, etc. means of solving the problem

[0013] To solve the above problems, the present invention provides a method for manufacturing medical nanofibers by: (a) mixing polyethylene oxide with water; (b) adding and mixing at least one of hyaluronic acid, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose, or carboxymethyl chitosan and menthol to 100 parts by weight of the mixed solution of step (a); (c) adding and mixing ethanol to the mixed solution of step (b); and (d) manufacturing the spinning solution of step (c) by electrospinning.

[0014] In addition, the present invention provides a method for manufacturing medical nanofibers characterized by the polyethylene oxide; at least one composition selected from hyaluronic acid, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose, or carboxymethyl chitosan; and a weight ratio of a mixture of water and ethanol of 3 to 10 to 0.5 to 5 to 75 to 85, wherein the weight ratio of ethanol to water is 9 to 1 to 2 to 1.

[0015] In addition, the present invention provides a biodegradable medical nanofiber having a diameter of 10 to 1000 nm, manufactured by the above method. Effects of the invention

[0017] The medical nanofiber of the present invention has excellent skin adhesion and absorption capacity, and is effective in reducing the heat sensation of wounds and blocking bacterial infection.

[0018] Furthermore, the present invention provides a burn treatment agent that allows for continuous application during the wound healing period, where rapid dressing is required in the treatment of burn wounds.

[0019] In addition, the present invention has the effect of preventing infection from the outside and having excellent exudate absorption capacity. Brief explanation of the drawing

[0021] FIG. 1 is a conceptual diagram showing that the nanospinning form of the present invention can be used with a tribostatic-based portable nanofiber manufacturing device. Figures 2 and 3 are enlarged photographs of an example of the medical nanofiber of the present invention. Specific details for implementing the invention

[0022] Preferred embodiments of the present invention will be described in detail below. First, in describing the present invention, specific descriptions of related known functions or configurations are omitted to avoid obscuring the essence of the invention.

[0023] Terms of degree used herein, such as ‘approximately’ and ‘substantially,’ are used to mean at or near the stated value when inherent manufacturing and material tolerances are presented in the stated meaning, and are used to prevent unscrupulous infringers from unfairly exploiting the disclosed content in which precise or absolute values ​​are mentioned to aid in understanding the invention.

[0024] The present invention relates to a method for manufacturing medical nanofibers, and

[0025] (a) a step of mixing polyethylene oxide and water; (b) a step of adding at least one of hyaluronic acid, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose, or carboxymethyl chitosan and menthol to 100 parts by weight of the mixed solution of step (a) and mixing; and (c) a step of adding ethanol to the mixed solution of step (b) and mixing; (d) a step of preparing the spinning solution of step (c) by electrospinning.

[0026] At this time, the content of the composition is at least one of the above-mentioned hyaluronic acid, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose, or carboxymethyl chitosan; the weight ratio of the mixture of water and ethanol is 3 to 10 to 0.5 to 5 to 75 to 85, and the weight ratio of ethanol to water is 9:1 to 2:1.

[0027] Polyethylene oxide is a linear crystalline polymer containing ether groups. Due to the ethylene oxide groups present in the repeating units, it exhibits excellent hydrophilicity and solubility. Furthermore, due to its high viscosity, it is utilized as a polymer electrolyte in lithium batteries. Additionally, it is soluble in various organic solvents in addition to water, possesses high gelling ability and low toxicity, and does not decompose over long periods. Consequently, it is widely used as a functional additive, such as a nonionic emulsifier, in the pharmaceutical, cosmetic, food, paper, and textile industries, as a component of biodegradable drug release systems, or as a drug delivery system or block copolymer.

[0028] The hyaluronic acid of the present invention is selected from Streptococcus zooepidemicus with a weight-average molecular weight of 100,000 to 1,600,000 Daltons (Da), more preferably 156,000 to 1,590,000 Daltons (Da), and is used in which the terminal groups are substituted with Na to increase solubility. At this time, if the weight-average molecular weight of the hyaluronic acid is less than 100,000 Daltons (Da), hydrolysis is too rapid and the stability of the final manufactured sheet decreases, and if it exceeds 1,600,000 Daltons (Da), the nanofiber manufacturing yield decreases, which is undesirable.

[0029] Polyvinyl alcohol (PVA) is also a linear crystalline polymer with hydroxyl groups. It is insoluble in organic solvents, exhibiting excellent solvent resistance. It also possesses surfactant properties, providing excellent emulsification and dispersion capabilities. Furthermore, it does not undergo decay, decomposition, or depolymerization and is physiologically harmless. As such, because polyvinyl alcohol has excellent solvent resistance, alkali resistance, and adhesive properties, it is widely utilized in various fields such as pharmaceuticals, cosmetics, and food. It is used as a material for materials like cardboard, veneer, and office adhesives to prevent cracking, as well as as a warp sizing agent for fibers, a thickening agent for color printing, and an emulsifier for emulsion or suspension polymerization. Additionally, it is used in materials for hydrogels for human organ replacement, drug delivery systems, bioreactors, and biosensors.

[0030] In addition, polyvinylpyrrolidone (PVP), alginate, carrageenan, or carboxymethyl chitosan are polymers that can be added to electrospinning, and the molecular weight of the water-soluble polymer is adjusted to within the range of Mv 100,000 to 1,000,000.

[0031] Various substances of flavoring agents and / or other additives, including menthol, may also be added here. For example, suitable flavoring agents include menthol, eugenol, spearmint, peppermint, cocoa, vanilla, cinnamon, lycorice, citrus or other fruit flavors and combinations thereof. Examples of non-flavoring additives include coolants, diluents, aerosol-forming agents and equivalents.

[0033] The features and other advantages of the present description as explained above will become more apparent from the embodiments described below, and

[0034] The following examples are described for illustrative purposes only and should not be interpreted as limiting or restricting the scope of protection of the present invention.

[0036] [Example 1]

[0037] 1. Weigh 3 mg of polyethylene oxide (PEO) on a precision scale.

[0038] 2. Place the Falcon tube on the still-life scale, zero it out, and add water until it reaches 18.75 mg.

[0039] 3. Slowly add Stirrer Powder No. 1 to Solution No. 2 while mixing.

[0040] 4. Add 4 mg of hyaluronic acid and 1 mg of menthol to solution 3.

[0041] 5. Stir the solution from No. 4 for 1 hour at 60°C to dissolve it thoroughly.

[0042] 6. Slowly add 56.25 mg of alcohol (ethanol) (density: 0.79 g / mL) to Solution 5 while stirring.

[0043] 7. Stir the solution from No. 6 at 60 degrees for 1 hour.

[0044] 8. Prepare a nanofiber solution by filling a syringe with solution No. 7 in 1 cc increments.

[0045] 9. Electrospinning the prepared nanofiber solution. (* For electrospinning, the portable tribostatic device of Registered Patent No. 10-2353832 may be used; refer to Fig. 1)

[0047] [Examples 2–12], [Comparative Examples 1–3]

[0048] The manufacturing method is the same as Example 1, except that the composition content of Tables 1 to 3 below is different.

[0050] [Materials Experiment]

[0051] The presence of nanofibers, diameter, nanofiber pores, and morphology were confirmed through SEM in Figures 2 and 3.

[0053] 1. Absorption (%): Nanofibers with a thickness of 1.0 mm are produced using a triboelectric generator, and the absorption is measured by cutting a 5x5 cm area. The initial weight of the glass is measured, and the weight (a) of a 5x5 cm sample is weighed. Distilled water is added at 10g, 20g, 30g, and 40g relative to the sample weight, and the samples are stored in a 37°C incubator for 24 hours. Afterward, the nanofiber is carefully suspended using tweezers for 30 seconds, and the weight is measured. Absorption (%) = W2 - W1 / W1 X 100

[0055] 2. Measurement of adhesion: A 1 mm thick nanofiber is fabricated on a stainless steel panel (50 x 125 mm), and the nanofiber is carefully separated by 10 mm from one end of the stainless steel. The specimen and panel are fixed at 180 degrees to a universal testing machine, and the load is measured by pulling at a speed of 5 mm / s.

[0057] 3. Bacterial barrier test: Tested according to EN 13726-5 bacterial barrier properties, bacterial properties and wet conditions. Nanofibers were fabricated to a size of 10 x 10 cm, and a 5 x 5 cm sample was cut from them for testing.

[0058] 1) Approximately 10 9 To obtain bacterial count / ml, Serratia marcescens (purchased from Culture of Serratia marcescens ATCC 8100) was cultured in nutrient broth at a temperature of 20–25°C for 24 hours.

[0059] Cultivate.

[0060] 2) Under sterile conditions, transfer a sterile dressing sample of at least 5 cm x 5 cm to a Petri dish filled with a sterile nutrient agar base.

[0061] 3) Divide the culture solution into 5 equal parts using a sterile pipette and place them at the four edges and the center.

[0062] 4) Incubate the plate at 20–25°C for 24 hours.

[0063] 5) After incubation, remove the liquid culture from the dressing using a sterile pipette, and remove the dressing from the agar surface using sterile forceps.

[0064] 6) Incubate for an additional 24 hours at 20–25°C.

[0065] 7) Check the plate for Serratia marcescens on the surface covered with the sample.

[0066] * Note: Serratia marcescens appears as vivid red growths on the surface of agar.

[0069] Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Comparative Example 2 Polyethylene oxide (mg) 3 5 7 10 12 0 Hyaluronic acid (mg) 4 4 4 4 4 4 Menthol (mg) 1 1 1 1 1 1 Water (mg) 18.75 18.75 18.75 18.75 18.75 18.75 Ethanol (mg) 56.25 56.25 56.25 56.25 56.25 56.25 Whether to fabricate tribostatic nanofibers O O O O O(Clumping occurs X Nanofiber diameter (nm) 150~350 150~350 150~350 150~350 200~550 - nanofiber density 0.72 1.28 1.41 1.59 1.84 -

[0070] As shown in Table 1, Comparative Example 2 does not have polyethylene oxide added, and Comparative Example 1 corresponds to a case where the weight ratio of polyethylene oxide to water and ethanol falls outside the range of 3~10 : 75~85, so in Comparative Example 1, the nanofibers clump together, and in Comparative Example 2, spinning is impossible.

[0072] Example 5 Example 6 Example 7 Comparative Example 3 Comparative Example 4 Polyethylene oxide (mg) 10 10 10 10 10 Hyaluronic acid (mg) 4 4 4 4 4 Menthol (mg) 1 1 1 1 1 Water (mg) 8.5 18.75 21.25 6.82 42.5 Ethanol (mg) 76.5 56.25 63.75 68.18 42.5 Whether to fabricate tribostatic nanofibers O O O 0 X Nanofiber diameter (nm) 100~200 150~350 200~550 50~150 Nanofiber density (mg / cm³) 1.48 1.56 1.72 0.09 - Absorption (%) 312.2±25.15 351.1±10.14 365.5±8.19 250.8±12.82 - adhesiveness 23.2±3.41 42.2±4.11 56.9±3.15 12.8±2.91 - Whether or not there is a bacterial barrier O O O X O

[0074] As shown in Table 2, Comparative Examples 3 and 4 are cases where the weight ratio of ethanol to water deviates from 9:1 to 2:1, where Comparative Example 3 is 10:1 and Comparative Example 4 is 1:1; in Comparative Example 3, no bacterial barrier is formed, and in Comparative Example 4, no nanofiber is produced.

[0076] Example 9 Example 10 Example 11 Comparative Example 5 Comparative Example 6 Polyethylene oxide (mg) 10 10 10 10 10 Hyaluronic acid (mg) 0.5 2 5 0 10 Menthol (mg) 1 1 1 1 1 Water (mg) 18.75 18.75 18.75 18.75 18.75 Ethanol (mg) 56.25 56.25 56.25 56.25 56.25 Whether to fabricate tribostatic nanofibers O O O O X Nanofiber diameter (nm) 150~350 150~350 250~500 150~350 - Nanofiber density (mg / cm³) 1.12 1.31 1.68 0.89 - Absorption (%) 151.1±7.12 266.7±25.15 387.1±8.26 123.8±5.61 - adhesiveness 5.8±2.21 19.2±5.18 72.2±7.61 3.6±1.04 - Whether or not there is a bacterial barrier O O O O O

[0078] Referring to Table 3, Comparative Examples 5 and 6 are cases where hyaluronic acid alone deviates from a weight ratio of 0.5 to 5 among at least one composition of hyaluronic acid, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), alginic acid, carrageenan, or carboxymethyl chitosan, and Comparative Example 5 has lower adhesive strength and absorption strength than the example, and Comparative Example 6 is difficult to produce nanofibers.

[0080] The present invention described above is not limited by the aforementioned embodiments and attached drawings, and it will be obvious to those skilled in the art that various substitutions, modifications, and changes are possible within the scope of the technical concept of the present invention.

Claims

Claim 1 A method for manufacturing medical nanofibers comprising: (a) a step of mixing polyethylene oxide and water; (b) a step of adding hyaluronic acid and menthol to 100 parts by weight of the mixed solution of step (a) in a weight ratio of 0.2 to 5 to 1 and mixing; (c) a step of adding ethanol to the mixed solution of step (b) and mixing; and (d) a step of preparing the spinning solution of step (c) by electrospinning, wherein the weight ratio of ethanol to water is 9:1 to 2:1 and the hyaluronic acid is 0.5 to 5 parts by weight per 100 parts by weight of the spinning solution. Claim 2 delete Claim 3 delete

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