Medical nanofiber membrane and support for breast reconstruction comprising same

Abstract

The purpose of the present disclosure is to provide a medical nanofiber membrane manufactured by electrospinning a polymer solution, comprising: polyethylene oxide; one or more natural polymers selected from hyaluronic acid, polyvinyl alcohol, polyvinyl pyrrolidone, alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose, and carboxymethyl chitosan; and an extracellular matrix. A support for breast reconstruction comprising the medical nanofiber membrane can improve tissue adhesion of a silicone implant by buffering a curved portion when the silicone implant is implanted in vivo during breast reconstruction surgery, and can improve in vivo retention after implantation.

Description

Medical nanofiber membrane and breast reconstruction support comprising the same

[0001] The present invention relates to a medical nanofiber membrane, a method for manufacturing the same, and a support for breast reconstruction.

[0002] The extracellular matrix (ECM) is a complex network that provides structural support to biological tissues and performs various physiological functions. It supports cells, regulates intercellular signaling, and plays a crucial role in tissue regeneration and repair. Recently, bioscaffolds utilizing ECM have attracted significant attention in the fields of tissue engineering and regenerative medicine. These bioscaffolds have been developed primarily to enhance biocompatibility, tissue integrity, and regenerative capacity.

[0003] Breast implant surgery uses implants to restore a resected breast. A tissue expander is inserted into the surgical site, gradually expanding the dermal tissue to create space for the implant. The implant is then inserted into the surgical site. While this procedure is simple and leaves no scars, it can cause a foreign body sensation after insertion and can lead to capsular contracture, a thick capsule forming around the implant that gradually hardens the surrounding muscles. Furthermore, it has a lower survival rate than autologous tissue.

[0004] To overcome these shortcomings, a method is used to eliminate foreign body sensation, suppress capsular contracture, and increase the survival rate by wrapping the breast implant with an extracellular matrix derived from homologous or xenogeneic dermal tissue after use. The extracellular matrix derived from dermal tissue is a dermal layer matrix obtained from human or animal skin through acellularization technology, and refers to a skin substitute composed of collagen, elastin, and fibronectin.

[0005] Meanwhile, the extracellular matrix scaffolds used in breast implants are expensive, limiting their economic viability. Furthermore, they suffer from poor quality, such as poor implantability when cut to size, and reduced shape retention due to volume loss after implantation. Therefore, the development of technologies to improve these issues is urgently needed.

[0006] The present disclosure aims to provide a medical nanofiber membrane having excellent biocompatibility and tissue regeneration ability.

[0007] Specifically, the present disclosure aims to provide a medical nanofiber membrane capable of assisting in spherical construction and tissue regeneration in silicone implants used in breast reconstruction, and a breast reconstruction support comprising the same.

[0008] In addition, the present disclosure aims to provide a method for manufacturing a medical nanofiber membrane, which can manufacture the nanofiber membrane economically and time-efficiently.

[0009] The medical nanofiber membrane of the present disclosure may be manufactured by electrospinning a polymer solution including: polyethylene oxide; one or more natural polymers selected from hyaluronic acid, hyaluronic acid, polyvinyl alcohol, polyvinyl pyrrolidone, alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose, and carboxylmethylchitosan; and an extracellular matrix.

[0010] The above extracellular matrix may include at least one selected from collagen, elastin, proteoglycan, glycosaminoglycan, and EGF.

[0011] The above polyethylene oxide may have a number average molecular weight of 10,000 to 2,000,000 g / mol.

[0012] The extracellular matrix may be contained in an amount of 1 to 20 wt% relative to the entire polymer solution.

[0013] The above polymer solution may contain 2 to 20 parts by weight of polyethylene oxide per 1 part by weight of natural polymer.

[0014] The above polymer solution may include a mixed solvent of water and ethanol.

[0015] The above mixed solvent may contain 1 to 10 parts by weight of ethanol per 1 part by weight of water.

[0016] The above medical nanofiber membrane may have an average diameter of 10 to 1000 nm.

[0017] The above medical nanofiber membrane may further comprise a drug selected from among an anti-inflammatory agent, an antibiotic, and an anticancer agent.

[0018] The present disclosure provides a support for breast reconstruction comprising a medical nanofiber membrane according to one embodiment of the present disclosure.

[0019] The present disclosure provides a method for producing a medical nanofiber membrane, comprising the steps of: preparing a polymer solution by dissolving polyethylene oxide; hyaluronic acid, at least one natural polymer selected from hyaluronic acid, polyvinyl alcohol, polyvinyl pyrrolidone, alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose, and carboxylmethylchitosan; and an extracellular matrix in a solvent; and electrospinning the polymer solution to produce a medical nanofiber membrane.

[0020] The above polymer solution may be composed of 3 to 10 wt% of polyethylene oxide, 0.5 to 5 wt% of natural polymer, 1 to 20 wt% of extracellular matrix, and 75 to 85 wt% of solvent.

[0021] The above electrospinning may be performed under conditions of a voltage of 10 to 200 V and a radiation distance of 5 to 50 cm.

[0022] The method for manufacturing the above medical nanofiber membrane may further include a step of removing residual solvent from the above medical nanofiber membrane.

[0023] The step of removing the residual solvent may be performed by using at least one method selected from a method of directly neutralizing an acid using an alkaline aqueous solution, a method of aging at room temperature, and a method of vacuum drying.

[0024] A medical nanofiber membrane according to one embodiment of the present invention exhibits excellent biocompatibility, in vivo persistence, and tissue adhesion, and thus can exhibit tissue regeneration and structural support effects when inserted into a living body.

[0025] A support for breast reconstruction according to one embodiment of the present invention can improve tissue adhesion of the prosthesis by cushioning a curved area when a silicone prosthesis used in breast reconstruction is implanted in a living body, and can improve retention in the body after implantation.

[0026] The method for manufacturing a medical nanofiber membrane according to one embodiment of the present invention is economical because it uses a small amount of human tissue during the manufacturing process, is manufactured in a non-contact manner, so the risk of infection is low, and is efficient because the treatment time can be reduced.

[0027] The present invention will be described in detail below. Terms used herein, unless specifically defined, should be interpreted as generally understood by those skilled in the art. The drawings and examples in this specification are intended to facilitate the understanding and practice of the present invention by those skilled in the art. Content that may obscure the gist of the invention may be omitted from the drawings and examples, and the present invention is not limited to the drawings and examples.

[0028] The singular forms used herein are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0029] Additionally, the numerical range used in the present invention includes lower and upper limits and all values ​​within that range, increments logically derived from the shape and width of the defined range, all doubly defined values, and all possible combinations of upper and lower limits of numerical ranges defined in different shapes. Unless otherwise specifically defined in the specification of the present invention, values ​​outside the numerical range that may arise due to experimental error or rounding of values ​​are also included in the defined numerical range.

[0030] In this specification, terms such as include, have, and have mean that a feature or component described in the specification exists, and unless specifically limited, do not preclude the possibility that one or more other features or components may be added.

[0031] Acellular dermis, a matrix conventionally used as an in vivo support, is very expensive and largely relies on imports, making its supply unstable. Furthermore, because it is often frozen for storage convenience, the collagen tissues within the acellular dermis are destroyed during freezing, leading to rapid degradation. In particular, during breast reconstruction, silicone implants are wrapped in a matrix and transplanted. However, due to the unevenness of the skin tissue, many tissues are discarded and cannot be used for transplantation. Furthermore, uneven thicknesses can lead to poor engraftment. Therefore, the present disclosure aims to provide a medical nanofiber membrane that is both economical and capable of stable in vivo engraftment.

[0032] The medical nanofiber membrane of the present disclosure is manufactured by electrospinning a polymer solution comprising: polyethylene oxide; one or more natural polymers selected from hyaluronic acid, polyvinyl alcohol, polyvinyl pyrrolidone, alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose, and carboxylmethylchitosan; and an extracellular matrix.

[0033] The medical nanofiber membrane of the present disclosure is manufactured by electrospinning a polymer solution containing the aforementioned composition, thereby providing a nanofiber membrane having superior adhesiveness and higher flexibility and elasticity than conventional membranes, and is advantageous for tissue reconstruction and support when inserted into a living body.

[0034] The above-mentioned extracellular matrix is ​​a major component of acellular dermal matrix (ADM), and acellular dermis is obtained by removing cells from skin dermal tissue. According to one embodiment, the extracellular matrix may include at least one selected from collagen, elastin, proteoglycan, glycosaminoglycan, and epidermal growth factor (EGF), and specifically may include collagen, elastin, proteoglycan, glycosaminoglycan, and EGF. These components perform important physiological functions such as structural support of tissue, cell signaling, cell migration, and cell differentiation, thereby improving biocompatibility and tissue integrity in reconstructive surgery.

[0035] According to one embodiment, the natural polymer may be hyaluronic acid.

[0036] According to one embodiment, the polyethylene oxide may have a number average molecular weight of 10,000 to 2,000,000 g / mol, the lower limit being 10,000, 20,000, 30,000, 40,000, 50,000, 60,000, 70,000, 80,000, 90,000 or 100,000 g / mol, and the upper limit being 2,000,000, 1,800,000, 1,600,000, 1,400,000, 1,200,000 or 1,000,000 g / mol.

[0037] According to one embodiment, the extracellular matrix may be contained in an amount of 1 to 20 wt% relative to the entire polymer solution, the lower limit may be 0.1, 0.3, 0.5, 0.8 or 1 wt%, and the upper limit may be 20, 19, 18, 17, 16, 15, 14, 13, 12, 11 or 10 wt%.

[0038] According to one embodiment, the polymer solution may contain 2 to 20 parts by weight of polyethylene oxide per 1 part by weight of the natural polymer, and specifically, the lower limit of the polyethylene oxide may be selected from 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, and 10 parts by weight, and the upper limit may be selected from 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, and 10 parts by weight, per 1 part by weight of the natural polymer.

[0039] According to one embodiment, the polymer solution may include a mixed solvent of water and ethanol.

[0040] According to one embodiment, the mixed solvent may contain 1 to 10 parts by weight of ethanol per 1 part by weight of water, and specifically, the lower limit of ethanol per 1 part by weight of water may be selected from 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, and 10 parts by weight, and the upper limit may be selected from 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, and 10 parts by weight.

[0041] According to one embodiment, the medical nanofiber membrane may have an average diameter of 10 to 1000 nm, specifically the lower limit may be 10, 50, 100, 150 or 200 nm, and the upper limit may be 1000, 900, 800, 700 or 600 nm.

[0042] According to one embodiment, the medical nanofiber membrane may further comprise an anti-inflammatory agent. The anti-inflammatory agent may be added to the polymer solution and used in a known effective amount. Specifically, the amount of the anti-inflammatory agent added may not exceed 10% by weight of the polymer solution, and more specifically, may range from 0.001 to 5% by weight.

[0043] Anti-inflammatory agents include, but are not limited to, one or more non-steroidal anti-inflammatory drugs selected from aspirin (acetylsalicylic acid), ibuprofen, naproxen, sulindac, diclofenac, piroxicam, ketoprofen, diflunisal, nabumerone, etodolac, oxalupozin, indomethacin, tolmetin, and plant-derived polyphenols with anti-inflammatory action.

[0044] The present disclosure provides a support for breast reconstruction comprising a medical nanofiber membrane according to any one of the claims of the present disclosure.

[0045] The above-mentioned breast reconstruction support may be formed by closely contacting the medical nanofiber membrane of the present disclosure as an acellular skin substitute with a prosthesis generally used in the art for insertion into a breast reconstruction site, and accordingly, seroma caused by the generation of dead space during prosthesis insertion can be reduced, thereby minimizing surgical side effects and preventing adhesion and capsular contracture.

[0046] In particular, the breast reconstruction support of the present disclosure can be easily implanted even at an uneven insertion site and stably perform the role of a support because the nanofiber film of the present disclosure is formed by closely attaching the nanofiber film of the present disclosure to the surface of the prosthesis by an electrospinning method.

[0047] According to one embodiment, the method for producing a medical nanofiber membrane of the present disclosure may include the steps of: preparing a polymer solution by dissolving polyethylene oxide; one or more natural polymers selected from hyaluronic acid, polyvinyl alcohol, polyvinyl pyrrolidone, alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose, and carboxylmethylchitosan; and an extracellular matrix in a solvent; and preparing a medical nanofiber membrane by electrospinning the polymer solution.

[0048] According to one embodiment, the polymer solution may be composed of 3 to 10 wt% of polyethylene oxide, 0.5 to 5 wt% of natural polymer, 1 to 20 wt% of extracellular matrix, and 75 to 85 wt% of solvent.

[0049] According to one embodiment, the electrospinning may be performed under conditions of a voltage of 10 to 200 V and a radiation distance of 5 to 50 cm, and specifically, may be performed under conditions of a voltage of 10 to 100 V. In addition, the average voltage of the electrospinning may be 5 to 50 V, 10 to 40 V, or 15 to 30 V.

[0050] The method for producing a medical nanofiber membrane of the present disclosure may further include a step of removing residual solvent from the medical nanofiber membrane.

[0051] The step of removing the residual solvent may be performed by using at least one method selected from a method of directly neutralizing an acid using an alkaline aqueous solution, a method of aging at room temperature, and a method of vacuum drying.

[0052] Hereinafter, the medical nanofiber membrane according to the present invention will be described in more detail through specific examples. However, the following examples are merely references for further explanation of the present invention and are not intended to limit the present invention, which may be implemented in various forms. Furthermore, the terminology used in the description of the present invention is merely intended to effectively describe specific embodiments and is not intended to limit the present invention.

[0053] [Examples 1 to 3 and Comparative Example 1]

[0054] A polymer solution was prepared with the composition shown in Table 1 below, and a medical nanofiber membrane was produced by electrospinning the polymer solution onto a stainless steel panel at a voltage of 10 to 100 V (average 20 V) using a portable nanofiber manufacturing device based on frictional electrostatics disclosed in patent publication KR 10-2021-0151311 A.

[0055] Comparative Example 1 Example 1 Example 2 Example 3 Polyethylene oxide (mg) 10 10 10 10 Hyaluronic acid (mg) 5 5 5 ECM (mg) 0 1 5 10 Water (mg) 18.7 5 18.7 5 18.7 5 18.7 5 Alcohol (mg) 56.2 5 6.2 5 6.2 5 5 6.2 5

[0056] [Evaluation Example 1] Adhesion Evaluation

[0057] A stainless steel panel measuring 50 x 125 mm was prepared, and the polymer solutions of Examples 1 and 2 and Comparative Example 1 were electrospun onto the stainless steel panel in the same manner as in the Examples and Comparative Examples, respectively, to produce a nanofiber membrane having a thickness of 1 mm. Thereafter, the stainless steel panel on which the nanofiber membrane was produced was fixed at 180 degrees to a universal testing machine, and the load was measured by pulling the universal testing machine at a speed of 5 mm / s, and the results are shown in Table 2 below.

[0058] A silicone pad measuring 50 x 125 mm was prepared, and the polymer solutions of Examples 1 and 2 and Comparative Example 1 were electrospun onto the silicone pad in the same manner as in Examples and Comparative Examples, respectively, to produce a nanofiber film. The film was then placed in a chamber at 37°C at an angle of 90 degrees and left for 1 minute. The remaining area was measured relative to the total area, and the results of determining the remaining % are shown in Table 2.

[0059] Example 1 Example 2 Comparative Example 1 Load (N) 72.5 ± 4.98 76.2 ± 5.75 56.5 ± 9.12 Residual Amount (%) 100 100 100

[0060] According to Table 2 above, it can be confirmed that the magnitude of the load measured in Examples 1 and 2 is greater than the magnitude of the load measured in Comparative Example 1. This indicates that the nanofiber film formed on the surface of the substrate according to the Examples was more strongly adhered than the nanofiber film of the Comparative Example. Accordingly, it is believed that when a polymer solution containing an extracellular matrix is ​​electrospun, a nanofiber film with superior adhesiveness can be formed.

[0061] As described above, the present invention has been described through specific matters and limited examples and comparative examples, but these are provided only to help a more general understanding of the present invention, and the present invention is not limited to the above examples, and those skilled in the art to which the present invention pertains can make various modifications and variations based on this description.

[0062] Therefore, the idea of ​​the present invention should not be limited to the described embodiments, and all things that are equivalent or equivalent to the claims described below as well as the claims are considered to fall within the scope of the idea of ​​the present invention.

Claims

1. Polyethylene oxide; One or more natural polymers selected from hyaluronic acid, hyaluronic acid, polyvinyl alcohol, polyvinyl pyrrolidone, alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose and carboxylmethylchitosan; and A medical nanofiber membrane manufactured by electrospinning a polymer solution containing an extracellular matrix.

2. In paragraph 1, A medical nanofiber membrane, wherein the extracellular matrix comprises at least one selected from collagen, elastin, proteoglycan, glycosaminoglycan, and EGF.

3. In paragraph 1, The above polyethylene oxide is a medical nanofiber membrane having a number average molecular weight of 10,000 to 2,000,000 g / mol.

4. In paragraph 1, A medical nanofiber membrane containing 1 to 20 wt% of an extracellular matrix relative to the entire polymer solution.

5. In paragraph 1, A medical nanofiber membrane, wherein the polymer solution contains 2 to 20 parts by weight of polyethylene oxide per 1 part by weight of natural polymer.

6. In paragraph 1, A medical nanofiber membrane, wherein the polymer solution comprises a mixed solvent of water and ethanol.

7. In paragraph 4, A medical nanofiber membrane, wherein the above mixed solvent contains 1 to 10 parts by weight of ethanol per 1 part by weight of water.

8. In paragraph 1, The above medical nanofiber membrane is a medical nanofiber membrane having an average diameter of 10 to 1000 nm.

9. In paragraph 1, A medical nanofiber membrane, wherein the medical nanofiber membrane further comprises a drug selected from among an anti-inflammatory agent, an antibiotic, and an anticancer agent.

10. A support for breast reconstruction comprising a medical nanofiber membrane according to any one of claims 1 to 8.

11. A step of preparing a polymer solution by dissolving polyethylene oxide; one or more natural polymers selected from hyaluronic acid, hyaluronic acid, polyvinyl alcohol, polyvinylpyrrolidone, alginic acid, carrageenan, chitin, chitosan, poloxamer, cellulose, and carboxylmethylchitosan; and an extracellular matrix in a solvent; A method for producing a medical nanofiber film, comprising: a step of producing a medical nanofiber film by electrospinning the above polymer solution; 12. In paragraph 10, A method for producing a medical nanofiber membrane, wherein the polymer solution is composed of 3 to 10 wt% of polyethylene oxide, 0.5 to 5 wt% of natural polymer, 1 to 20 wt% of extracellular matrix, and 75 to 85 wt% of solvent.

13. In paragraph 10, A method for manufacturing a medical nanofiber film, wherein the above electrospinning is performed under the conditions of a voltage of 10 to 200 V and a spinning distance of 5 to 50 cm.

14. In paragraph 10, A method for producing a medical nanofiber membrane, further comprising a step of removing residual solvent from the medical nanofiber membrane.

15. In paragraph 13, A method for producing a medical nanofiber membrane, wherein the step of removing the residual solvent uses at least one method selected from a method of directly neutralizing an acid using an alkaline aqueous solution, a method of aging at room temperature, and a method of vacuum drying.