Method for manufacturing medical nanofibers, and medical nanofibers manufactured thereby

Abstract

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

Description

Method for manufacturing medical nanofibers and medical nanofibers obtained thereby

[0001] The present invention relates to a method for manufacturing medical nanofibers and medical nanofibers produced thereby, and more specifically, to a method for manufacturing medical nanofibers using highly absorbent electrostatic electricity using a water-soluble polymer, and characterized in that the nanofibers have improved cooling function and skin adhesion.

[0002] The rapid growth of an aging society and the rise in metabolic diseases have led to a surge in patients with chronic wounds, garnering significant attention to chronic wound treatment. Chronic wounds are defined as wounds that do not heal after a period of normal wound healing. This period typically lasts from four weeks to three months, and even with normal wound care and treatment, less than 20-30% of the wound remains unhealed.

[0003] Unlike general wound treatments, chronic wound treatment products come in various types of dressings depending on the amount of exudate. Recently, antibacterial dressings, functional dressings that relieve pain, and cell therapy products that promote wound healing have been developed and are being used for chronic wounds that are difficult to heal. In addition, wound treatment products are classified into film, foam, hydrogel, and hydrocolloid types according to their raw materials, and the raw materials are becoming increasingly diverse, such as the use of bio-derived materials. In order for wound healing to proceed quickly, it is important to absorb exudate well, prevent the wound area from being exposed to the outside, and maintain a moist state. This promotes epithelial cell regeneration rather than the healing process of forming an eschar.

[0004] Accordingly, there has been an increase in the number of cases in which bio-derived polymers are used to overcome the problems of biodegradable synthetic polymers.

[0005] As a representative bio-derived polymer, hyaluronic acid is a biosynthetic natural substance found in abundance in animal skin. It is a natural polymer widely used as a support material for tissue culture due to its excellent biocompatibility and biodegradability.

[0006] Hyaluronic acid has a large number of hydroxyl groups (-OH) in its molecules, making it hydrophilic, and due to the positive charge of the polymer itself, there are limitations in electrospinning hyaluronic acid as a single material, and therefore, there have been no reports on the production of nanofibers by electrospinning.

[0007] Accordingly, medical nanofibers with excellent absorbency, adhesiveness, and antibacterial properties were manufactured by nanospinning using a solution containing hyaluronic acid using electrostatic friction.

[0008] The purpose of the present invention is to provide a medical nanofiber using electrostatic electricity that maintains a moist environment between a wound and a dressing material, has appropriate absorbency and moisture permeability, prevents drying of the wound surface, prevents maceration of surrounding normal skin, and also allows gas exchange, prevents bacterial invasion from the outside, and adheres to the wound surface during exchange, causing less damage to new tissues.

[0009] In order to solve the above problems, the present invention provides a method for producing medical nanofibers, comprising the steps of (a) mixing polyethylene oxide and water; (b) adding at least one of hyaluronic acid, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose, or carboxylmethyl chitosan and menthol to 100 parts by weight of the mixed solution of step (a) and mixing; and (c) adding ethanol to the mixed solution of step (b) and mixing; and (d) producing the spinning solution of step (c) by electrospinning.

[0010] In addition, the present invention provides a method for manufacturing a medical nanofiber, characterized in that the composition comprises at least one of the polyethylene oxide; hyaluronic acid, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose, or carboxylmethyl chitosan; and a weight ratio of a mixture of water and ethanol is 3 to 10 to 0.5 to 5 to 75 to 85, and the weight ratio of the ethanol to water is 9:1 to 2:1.

[0011] In addition, the present invention provides a biodegradable medical nanofiber having a diameter of 10 to 1000 nm, manufactured by the above method.

[0012] The medical nanofiber of the present invention has excellent skin adhesion and absorbency, and has the effect of reducing the sensation of heat in a wound and blocking bacterial infection.

[0013] In addition, the present invention provides a burn treatment agent that requires rapid dressing in treating burn wounds and can be continuously used during the wound treatment period.

[0014] In addition, the present invention has the effect of preventing infection from the outside and has excellent exudate absorption ability.

[0015] Figure 1 is a conceptual diagram showing how the nano-radiation form of the present invention can be used in a friction-electrostatic-based portable nanofiber manufacturing device.

[0016] Figures 2 and 3 are enlarged photographs of examples of medical nanofibers of the present invention.

[0017] Hereinafter, preferred embodiments of the present invention will be described in detail. First, in describing the present invention, specific descriptions of related known functions or configurations will be omitted to avoid obscuring the gist of the present invention.

[0018] The terms "about," "substantially," and the like used in this specification are used in a meaning that is at or close to the numerical value when manufacturing and material tolerances inherent to the meanings mentioned are presented, and are used to prevent unscrupulous infringers from unfairly exploiting the disclosure in which exact or absolute numerical values ​​are mentioned to aid understanding of the present invention.

[0019] The present invention relates to a method for manufacturing medical nanofibers.

[0020] (a) a step of mixing polyethylene oxide and water; (b) a step of adding at least one of hyaluronic acid, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose, or carboxylmethylchitosan 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 spinning solution of step (c) is prepared by electrospinning.

[0021] At this time, the content of the composition is at least one of the hyaluronic acid, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose or carboxylmethyl chitosan; the weight ratio of the water and ethanol mixture is 3 to 10 to 0.5 to 5 to 75 to 85, and the weight ratio of the ethanol to water is appropriately 9:1 to 2:1.

[0022] Polyethylene oxide is a linear crystalline polymer with an ether group. It has excellent hydrophilicity and solubility due to the ethylene oxide group present in the repeating unit. Due to its high viscosity, it is not only used as a polymer electrolyte in lithium batteries, but also dissolves in various organic solvents other than water and has high gelling ability and low toxicity. It does not decompose over a long period of time, so it is widely used as a functional additive such as a nonionic emulsifier in pharmaceuticals, cosmetics, food, paper, and textile industries, as a component of a biodegradable drug release system as a drug delivery vehicle or block copolymer.

[0023] The hyaluronic acid of the present invention is selected from those having a weight average molecular weight of 100,000 to 1,600,000 Daltons (Da), more preferably 156,000 to 1,590,000 Daltons (Da), extracted from Streptococcus zooepidemicus, and those having terminal groups 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 is low, and if it exceeds 1,600,000 Daltons (Da), the yield of nanofiber manufacturing is low, which is not preferable.

[0024] Polyvinyl alcohol (PVA) is also a linear crystalline polymer with hydroxyl groups. It has excellent solvent resistance because it does not dissolve in organic solvents, and has excellent emulsifying / dispersing ability due to its surfactant properties. It does not decay, decompose, or depolymerize, and is physiologically harmless. Because polyvinyl alcohol has excellent solvent resistance, alkali resistance, and adhesiveness, it is used in various fields such as pharmaceuticals, cosmetics, and food, as well as in materials such as cardboard, veneer, and office adhesives to prevent cracking, warp sizing agents for textiles, thickeners for color printing, and emulsifiers for emulsion or suspension polymerization, as well as in hydrogels for human organ replacement, drug delivery systems, bioreactors, and biosensors.

[0025] In addition, polyvinylpyrrolidone (PVP), alginic acid, carrageenan, or carboxylmethylchitosan are polymers that can be added to electrospinning, and the molecular weight of the water-soluble polymer is adjusted to be within the range of Mv 100,000 to 1,000,000.

[0026] Various substances, including flavoring agents and / or other additives, may also be added here, including menthol. For example, 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 refrigerants, diluents, aerosol formers, and the like.

[0027]

[0028] The features and other advantages of this description as described above will become more apparent from the embodiments described below.

[0029] The following examples are provided for illustrative purposes only and are not to be construed as limiting or restricting the scope of protection of the present invention.

[0030]

[0031] [Example 1]

[0032] 1. Weigh 3 mg of polyethylene oxide (PEO) on a precision scale.

[0033] 2. Place the Falcon tube on the still water scale, adjust the zero point, and add 18.75 mg of water.

[0034] 3. Slowly add stirrer 1 powder to solution 2 and mix.

[0035] 4. Add 4 mg of hyaluronic acid and 1 mg of menthol to solution 3.

[0036] 5. Stir the solution 4 at 60℃ for 1 hour to ensure it is fully dissolved.

[0037] 6. Slowly add 56.25 mg of alcohol (ethanol) (density: 0.79 g / mL) to solution 5 while rotating it on a stirrer.

[0038] 7. Stir solution 6 at 60 degrees for 1 hour.

[0039] 8. Prepare a nanofiber solution by filling the syringe with solution 7 in 1 cc units.

[0040] 9. Electrospinning the manufactured nanofiber solution. (* Electrospinning can be performed using the friction electrostatic portable device of Patent No. 10-2353832, see Figure 1.)

[0041]

[0042] [Examples 2-12], [Comparative Examples 1-3]

[0043] The only difference is the composition content in Tables 1 to 3 below, and the remaining manufacturing method is the same as Example 1.

[0044]

[0045] [Physical Properties Experiment]

[0046] Whether nanofibers were manufactured, their diameter, nanofiber pores, and shape were confirmed through SEM in Figures 2 and 3.

[0047]

[0048] 1. Absorbency (%): Using a friction electrostatic generator, create nanofibers with a thickness of 1.0 mm, cut an area of ​​5x5 cm in length and width, and measure the absorbency. Measure the initial weight of the glass sale, cut the sample into 5x5 cm sizes, measure the weight (a), add distilled water in amounts of 10g, 20g, 30g, and 40g of the sample weight, store in a 37°C thermostat for 24 hours, and then carefully hang the nanofibers with tweezers for 30 seconds and measure the weight. Absorbency (%) = W2-W1 / W1 X 100

[0049]

[0050] 2. Adhesion measurement: Fabricate 1 mm thick nanofibers on a stainless steel panel (50 x 125 mm), and carefully separate the nanofibers 10 mm from one end of the stainless steel. Fix the specimen and panel at a 180 degree angle on a universal testing machine, pull at a speed of 5 mm / s, and measure the load.

[0051]

[0052] 3. Bacterial barrier test: Tested according to EN 13726-5 bacterial barrier properties, bacterial properties and wet conditions. Nanofibers were manufactured to a size of 10 x 10 cm, and 5 x 5 cm samples were cut and tested.

[0053] 1) About 10 9 To obtain the number of bacteria / ml, Serratia marcescens (purchased from Culture of Serratia marcescens ATCC 8100) was cultured in nutrient broth at 20-25℃ for 24 hours.

[0054] Cultivate.

[0055] 2) Under sterile conditions, transfer a sterile dressing sample of at least 5 cm X 5 cm to a petri dish filled with sterile nutrient agar base.

[0056] 3) Divide the culture solution into five equal parts using a sterile pipette and place them on the four edges and in the center.

[0057] 4) Incubate the plate at 20-25℃ for 24 hours.

[0058] 5) After culturing, remove the liquid culture from the dressing using a sterile pipette and remove the dressing from the agar surface using sterile forceps.

[0059] 6) Incubate at 20-25℃ for an additional 24 hours.

[0060] 7) Check the plate to see if Serratia marcescens is present on the surface covered with the sample.

[0061] * Note: Serratia marcescens appears as bright red growths on the agar surface.

[0062] Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Comparative Example 2 Polyethylene oxide (mg) 35710120 Hyaluronic acid (mg) 4444444 Menthol (mg) 111111 Water (mg) 18.7518.7518.7518.7518.7518.75 Ethanol (mg) 56.2556.2556.2556.2556.25 Whether or not friction electrostatic nanofibers are produced OOOOO (no lumps are formed X Nanofiber diameter (nm) 150~350 150~350 150~350 150~350 200~550 - Nanofiber density 0.72 1.28 1.4 11.59 1.84 -

[0063] As shown in Table 1, Comparative Example 2 did not contain polyethylene oxide, and Comparative Example 1 corresponds to a case where the weight ratio of polyethylene oxide to water and ethanol was outside the range of 3 to 10: 75 to 85. In Comparative Example 1, a phenomenon of nanofibers clumping occurred, and in Comparative Example 2, spinning was impossible.

[0064] 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 Menthol (mg) 1 1 1 1 Water (mg) 8.5 1 8.7 5 2 1.2 5 6.8 2 4 2.5 Ethanol (mg) 7 6.5 5 6.2 5 6 3.7 5 6 8.1 8 4 2.5 Friction electrostatic nanofiber production status OOO 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 - Absorbency (%) 312.2 ± 25.15 35 1.1 ± 10.14 36 5.5 ± 8.19 25 0.8 ± 12.82 - Adhesion 23.2 ± 3.4 14 2.2 ± 4.1 15 6.9 ± 3.15 12.8 ± 2.91 - Bacterial barrier OOOXO

[0065] As shown in Table 2, Comparative Examples 3 and 4 are cases where the weight ratio of ethanol to water is outside the range of 9:1 to 2:1. Comparative Example 3 is a case where ethanol to water is 10:1, and Comparative Example 4 is a case where ethanol to water is 1:1. In Comparative Example 3, no bacterial barrier is generated, and in Comparative Example 4, no nanofibers are produced.

[0066]

[0067] 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) 11 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 Friction electrostatic nanofiber production status OOOOOX Nanofiber diameter (nm) 150~350 150~350 250~500 150~350 - Nanofiber Density (mg / cm3) 1.121.311.680.89-Absorbency (%) 151.1±7.12266.7±25.15387.1±8.26123.8±5.61-Adhesion 5.8±2.2119.2±5.1872.2±7.613.6±1.04-Whether it is a bacterial barrier OOOOO

[0068] Referring to Table 3, Comparative Examples 5 and 6 are compositions in which at least one of hyaluronic acid, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), alginic acid, carrageenan, or carboxylmethyl chitosan contains hyaluronic acid alone in a weight ratio of 0.5 to 5. In Comparative Example 5, the adhesive strength and absorbency are lower than those of the examples, and in Comparative Example 6, it is difficult to produce nanofibers.

[0069]

[0070] The present invention described above is not limited to the above-described embodiments and the attached drawings, and it will be apparent to a person skilled in the art to which the present invention pertains that various substitutions, modifications, and changes are possible within the scope that does not depart from the technical spirit of the present invention.

Claims

1. (a) A step of mixing polyethylene oxide and water; (b) a step of adding and mixing at least one of hyaluronic acid, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose or carboxyl methyl chitosan and menthol to 100 parts by weight of the mixed solution of step (a); and (c) a step of adding ethanol to the mixed solution in step (b) and mixing; (d) A method for producing medical nanofibers by producing the spinning solution of step (c) by electrospinning.

2. In paragraph 1, The above polyethylene oxide; A composition comprising at least one of hyaluronic acid, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose or carboxylmethylchitosan; The weight ratio of the water and ethanol mixture 3~10 to 0.5~5 to 75~85, A method for manufacturing medical nanofibers characterized by a weight ratio of ethanol to water of 9:1 to 2:

1.

3. Manufactured according to the above clause 1 or 2, Biodegradable medical nanofibers with a diameter of 10–1000 nm.

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