KR20220132370A - Manufacturing method of medical nanosheets using polycaprolactone, medical nanosheets manufactured by this method - Google Patents

Abstract

The present invention relates to a method for manufacturing a medical nanosheet using polycaprolactone and a medical nanosheet manufactured therefrom and, more particularly, to a method for manufacturing a medical nanosheet using polycaprolactone to enable mass production through a multi-nozzle while having biocompatibility and to a medical nanosheet manufactured therefrom. According to the present invention, a medical nanosheet is manufactured by dissolving the polycaprolactone in two or more kinds of organic solvents to prepare a polycaprolactone solution having a concentration of 6 to 14 wt%, and electrospinning the prepared polycaprolactone solution with the multi-nozzle, thereby minimizing side effects with the skin due to biocompatibility, and facilitating mass production to be used as various products like hemostats.

Description

Manufacturing method of medical nanosheets using polycaprolactone, medical nanosheets prepared therefrom

The present invention relates to a method for manufacturing a medical nanosheet using polycaprolactone, and to a medical nanosheet manufactured therefrom, and more particularly, to a medical use using polycaprolactone to enable mass production through multi-nozzle while having biocompatibility. It relates to a method for manufacturing a nanosheet, and to a medical nanosheet prepared therefrom.

In general, medical nanosheets are sheet-shaped products made up of healthcare fibers related to life, health maintenance and promotion, or fibers for surgery and treatment. , tissue adhesion prevention pads, biodegradable sutures for surgery, and products such as hemostats.

Among them, hemostat is used for the purpose of stopping bleeding symptoms, and it can be said that it is an important surgical medical product that can be applied from mild bleeding caused by abrasions to large bleeding caused by various reasons such as surgery and accidents.

In other words, the hemostasis that occurs in the human body is physiologically very complex, so there is a limit to completely preventing bleeding. For example, in the case of serious tissue damage due to an unexpected accident or excessive bleeding that may occur during surgical procedures during surgery, the use of a hemostat cannot be used to completely stop the bleeding only with the physical and chemical hemostatic action that naturally functions in the human body. will become

These hemostats should not only be capable of complete hemostasis and wound healing, but also should not have side effects and toxicity such as fever or inflammation when applied to the human body. In order to induce hemostasis by the recruitment of blood coagulation factors related to hemostasis, a certain level of water absorption is required.

In relation to this, in 'Improved absorbent hemostatic agent and its manufacturing method (registration number: 10-1624625)', oxidized regenerated cellulose made by oxidizing oxidized regenerated cellulose (ORC), which is an absorbent fabric or knitted fabric, among products developed as hemostats. is starting According to the principle of hemostatic action, it does not participate in the blood coagulation process in vivo, and when it comes into contact with blood at the bleeding site, it swells and covers the bleeding site, thereby constricting the tissue around the blood vessel to stop hemostasis. However, oxidatively regenerated cellulose is acidic during hemostasis, and there is a risk of denaturing the activity of blood clotting factors such as thrombin and fibrinogen, which are involved in the blood clotting process.

Accordingly, hemostats containing blood coagulation factors such as thrombin and fibrinogen and prepared in the form of absorbent nonwoven fabrics, fabrics, or knitted fabrics have been proposed, but there is a disadvantage that the hemostatic effect and the wound healing effect are not sufficient.

In addition, an alginic acid sponge prepared by freeze-drying a hydrogel formed by dissolving alginic acid or an alkali metal salt of alginic acid at a certain concentration has also been proposed, but this also does not have a satisfactory hemostatic effect and wound healing effect.

In addition, some products developed as hemostats have a problem that, when applied to the human body, causes side effects, such as burning or cytotoxicity, in the tissues surrounding the application site, and some of the hemostats are biocompatible. Since this is insignificant, there is a problem that is not suitable for surgical operation. In particular, medical nanosheets such as hemostatic cells according to the above are difficult to continuously mass-produce, so there is an undesirable problem in terms of production efficiency.

Therefore, there is a need for technology development for medical nanosheets that can be mass-produced while minimizing side effects on the human body due to excellent biocompatibility.

Registered in Korea Patent Publication No. 10-1624625, 2016.05.20.

The present invention was invented to solve the above problems, and it provides a method for manufacturing a medical nanosheet using polycaprolactone to enable mass production through a multi-nozzle while having biocompatibility, and a medical nanosheet manufactured therefrom make it a technical solution.

In order to solve the above technical problem, the present invention provides a first step of dissolving polycaprolactone in two or more organic solvents to prepare a polycaprolactone solution having a concentration of 6 to 14 wt%; and a second step of manufacturing a nanosheet while electrospinning the polycaprolactone solution to be discharged in the form of a filament, wherein the second step includes electrospinning the polycaprolactone solution upward from the multi-nozzle, Preparation of medical nanosheets using polycaprolactone, characterized in that continuous electrospinning by applying a voltage of 10 to 50 kV at a flow rate of 200 to 800 μl/min by adjusting the tip to collector distance (TCD) to 250 to 350 mm provide a way

In order to solve the above other technical problems, the present invention provides a medical nanosheet, characterized in that produced by the method.

According to the method for manufacturing a medical nanosheet using polycaprolactone of the present invention by means of a solution to the above problem, by electrospinning using polycaprolactone, which is a biocompatible or biocompatible polymer, the healing rate of the wound is increased and the recovery rate is increased. Not only can the possibility of bleeding be minimized, but it has the effect of manufacturing a nanosheet with reduced side effects to the human body.

In addition, since electrospinning can be performed by installing up to 4 multi-nozzles with about 14 nozzle tips arranged, continuous electrospinning is possible than when a single nozzle is installed, which has the effect of mass-producing nanosheets. have.

1 is a flowchart showing a method of manufacturing a medical nanosheet according to the present invention.
2 is a photograph showing a state in which the polycaprolactone solution according to the present invention is electrospun.
3 is a photograph showing a medical nanosheet according to the present invention.
4 is a SEM photograph showing a medical nanosheet according to Example 1.

Hereinafter, the present invention will be described in detail.

1 is a flowchart showing a method for manufacturing a medical nanosheet according to the present invention. Referring to FIG. 1 , the medical nanosheet of the present invention comprises a first step (S20) of dissolving polycaprolactone in two or more organic solvents to prepare a polycaprolactone solution having a concentration of 6 to 14 wt% (S20), and a polycaprolactone solution It can be produced through the second step (S20) of producing a nanosheet while being discharged in the form of a filament by electrospinning.

In order to prepare the medical nanosheet as described above, the first step is to prepare a polycaprolactone solution having a concentration of 6 to 14 wt% by dissolving polycaprolactone in two or more organic solvents (S20).

Before the description, polycaprolactone (polycaprolactone) is a biocompatible polymer, non-toxicity (non-toxicity), non-carcinogenicity (non-carcinogenicity), biodegradability (biodegradability), biocompatibility (biocompatibility), excellent mechanical properties (high mechanical properties) and high water content.

By dissolving polycaprolactone having such characteristics in two or more organic solvents at room temperature, a polycaprolactone solution having a concentration of 6 to 14 wt% can be prepared. In the case of organic solvents, two or more types can be applied in various ways, for example, a solution in which dimethylformamide (DMF) and chloroform are mixed in a volume ratio of 10 to 40: 60 to 90 can be used as the organic solvent.

The concentration of the polycaprolactone solution prepared through this process may be in the range of 6 to 14 wt% in order to achieve the optimal performance of electrospinning, and the problem with the concentration of the polycaprolactone solution being less than 6 wt% or exceeding 14 wt% is As follows.

As the concentration of the polycaprolactone solution approaches 6wt%, the viscosity decreases as the concentration of the polycaprolactone solution decreases, and by accelerating the consumption rate of the polycaprolactone solution during electrospinning, it is possible to improve the hardening of the taylor cone. . At this time, the viscosity of the polycaprolactone solution depends on the attractive and repulsive forces between polycaprolactones, and since it shows the characteristics of intermolecular interactions, it can be said to be an important factor affecting the fiber formation and average diameter.

Therefore, when the concentration of the polycaprolactone solution is less than 6wt%, the concentration is too low and the biocompatibility of the nanosheet is insignificant. Accordingly, there is a problem that it cannot be made into a nanosheet form.

When the concentration of the polycaprolactone solution exceeds 14 wt%, it takes more than 40 minutes to fill the polycaprolactone solution for electrospinning, and since the viscosity increases, even if the flow rate exceeds 800 μl/min during electrospinning, the syringe A blurring phenomenon will occur.

As a result, not only the injection itself does not work, but also the taylor cone is not maintained. In other words, due to the nature of the organic solvent, the volatilization rate is fast, and the taylor cone becomes opaque as time elapses while the taylor cone is formed during electrospinning, and the taylor cone may harden. It's important not to do that.

As such, due to the increase in viscosity, agglomeration occurs in the polycaprolactone solution, or filament-type fibers discharged during the electrospinning process agglomerate, resulting in no productability. Therefore, when the concentration of the polycaprolactone solution exceeds 14 wt%, the thickness of the electrospun filament is very thick and it is difficult to discharge or fiberization itself. desirable.

Next, the second step is a step of producing a nanosheet while electrospinning a polycaprolactone solution and discharged in the form of a filament (S20).

In the present invention, electrospinning applies an electric field greater than the surface tension of the polycaprolactone solution to form fibers as the taylor cone formed at the tip of the nozzle tip 121 is splitting, which is the polycaprolactone according to the present invention. It can be seen through FIG. 2 showing the electrospinning state of the lactone solution.

2 is an enlarged photograph of the electrospinning machine 100 that enables the polycaprolactone solution to be electrospun, and the lower holder 110 and the holder 110 at regular intervals along the transverse or longitudinal direction. A plurality of multi-nozzles 120 are disposed as, a nozzle tip 121 installed at regular intervals along the longitudinal direction on the upper surface of the multi-nozzle 120, and a predetermined spaced apart position on the upper portion of the cradle 110 It may be configured to include a collector 130 that is Referring to part A of FIG. 2 , it can be seen that the fiber in a droplet state being electrospun from the nozzle tip 121 to the collector 130 disposed at a predetermined distance from the nozzle tip 121 to the upper portion of the multi-nozzle 120 can be seen.

Using the electrospinning machine 100 shown in FIG. 2, the polycaprolactone solution is electrospun upward from the multi-nozzle 120, and 200 to 800 μl/ By continuously electrospinning by applying a voltage of 10 to 50 kV at a flow rate of min, it is possible to manufacture a nanosheet in the form of a nonwoven fabric. When the polycaprolactone solution formed on the nozzle tip 121 needs to be removed while the polycaprolactone solution is electrospinning through the electrospinning machine 100, a rubber material having an insulating effect is wrapped around a wooden stick. It is preferable to use a tool of the form.

Here, the collector 130 is to provide a space in which the nanofilaments electrospun from the nozzle tip 121 can be stacked, and as the distance between the collector 130 and the nozzle tip 121 is narrower, the nozzle tip 121 It is important to match the optimal distance because the force that the polycaprolactone solution is radiated upward increases and the force decreases as the distance between the collector 130 and the nozzle tip 121 increases.

If the distance between the collector 130 and the nozzle tip 121 during electrospinning, that is, the TCD is controlled to be less than 250 mm, the distance between the collector 130 and the nozzle tip 121 is too narrow, so the collector ( 130), so that polycaprolactone discharged in the form of droplets from the nozzle tip 121 is difficult to make a flat surface of the nanosheet.

If the TCD is adjusted to exceed 350mm, the distance between the collector 130 and the nozzle tip 121 may be too far and the electrospinning performance may decrease, and the nozzle tip 121 and the collector 130 are discharged because the distance is long. There is a disadvantage in that the thickness of the fibers is inevitably not constant, and thus the productability is lost.

For this reason, the distance between the collector 130 and the nozzle tip 121 is preferably adjusted within the range of 250 to 350 mm, and for electrospinning in a stable fiber form, the TCD is most preferably 280 mm.

When the electrospinning flow rate is less than 200 μl/min, the polycaprolactone solution is condensed on the nozzle tip 121, making it difficult to stably electrospinning. There are disadvantages in that unstable spinning and non-uniform filament thickness can be formed. If the polycaprolactone solution is electrospinning at a flow rate exceeding 800 μl/min, this also prevents the polycaprolactone solution from forming on the nozzle tip 121 or overflowing, so that the discharged filament cannot form a uniform fibrous shape. There is a downside to being

When electrospinning, the voltage is preferably controlled within the range of 10 to 50 kV. If the voltage is less than 10kV, electrospinning cannot be started, so radiation is very reduced and a voltage of at least 10kV must be supplied. can't In addition, since the fiber aggregation phenomenon is seen in the low voltage section where the voltage is less than 10 kV, it is not preferable. On the other hand, if it exceeds 50 kV, the radiation increases, but the radiation proceeds as it is easily cut off and splits to form an unstable jet, as well as the physical properties of the polycaprolactone solution being electrospinning, so that the voltage exceeds 50 kV It is recommended not to set it. For efficient operation of the electrospinning performance, it is most preferable to use a voltage of 30 kV.

In the electrospinning process, the left and right moving distance of the collector 130 is preferably 80 mm, since the collector 130 can be moved in the left and right directions in a wide range of 80 mm, 0.19 to 0.28 μm while being wound using a roller It becomes possible to manufacture nanosheets distributed with thin and uniform fibers of

3 is a photograph showing a medical nanosheet according to the present invention. Referring to Figure 3, the TCD is adjusted to 250 to 350 mm, and a voltage of 10 to 50 kV is applied at a flow rate of 200 to 800 μl/min to continuously electrospinning, so that the nanosheets in the form of a nonwoven fabric can be confirmed. do.

Through the electrospinning using the multi-nozzle 120 as described above, the polycaprolactone solution forming phenomenon is less and the nanosheet is stably electrospun to produce a nanosheet distributed in a uniform and thin thickness, in particular, electrospinning using a single nozzle Since continuous electrospinning is possible, there is an advantage in mass production of nanosheets.

Hereinafter, an embodiment of the present invention will be described in more detail as follows. However, the following examples are merely illustrative to help the understanding of the present invention, and the scope of the present invention is not limited thereby.

<Example 1>

A solution of polycaprolactone (Mw: 80,000 g/mol, Sigma aldrich) mixed with dimethylformamide and chloroform in a 15:85 booby ratio was used as an organic solvent and stirred until completely dissolved at room temperature. A lactone solution was prepared.

After adjusting the distance between the nozzle tip of the electrospinning machine and the collector to 280 mm, a 6wt% polycaprolactone solution was electrospun while applying a voltage of 30 kV at a flow rate of 500 μl/min to prepare a nonwoven nanosheet.

4 is an SEM photograph of the medical nanosheet according to Example 1. 4(a), 4(b), 4(c), and 4(d) are SEM images of the nanosheets enlarged at different magnifications, respectively. It is confirmed that the filaments constituting the overall exhibit a uniform fibrous shape and the thickness of each filament is distributed in the range of 0.19 to 0.28 μm. Through this, it can be seen that if the thickness of the filament is less than 0.19 μm, the durability of the nanosheet is not good, and if it exceeds 0.28 μm, it is undesirable in terms of improving physical properties.

In summary, the present invention relates to a method for manufacturing a medical nanosheet using polycaprolactone, by dissolving polycaprolactone in two or more organic solvents to prepare a polycaprolactone solution having a concentration of 6 to 14 wt%, By electrospinning the polycaprolactone solution upward from the multi-nozzle 120, nanosheets can be continuously mass-produced.

Therefore, according to the present invention, polycaprolactone, which is a biocompatible or biocompatible polymer, is used, and the distance between the nozzle tip 121 and the collector 130 is adjusted to 250 to 350 mm at a flow rate of 200 to 800 μl/min. By continuously electrospinning while applying a voltage of 50 kV to 50 kV, it is possible to increase the healing rate of the wound site and minimize the possibility of rebleeding, as well as electrospinning through a conventional single nozzle to produce a nanosheet, unlike the multi-nozzle ( 120) through continuous electrospinning, which is significant in that the production efficiency of nanosheets can be maximized.

The above description is merely illustrative of the technical idea of the present invention, and various modifications and variations will be possible without departing from the essential characteristics of the present invention by those skilled in the art to which the present invention pertains. Therefore, the embodiments disclosed in the present invention are not intended to limit the technical spirit of the present invention, but to illustrate, and the scope of the technical spirit of the present invention is not limited by these embodiments. The protection scope of the present invention should be construed by the claims, and all technical ideas within the scope equivalent thereto should be construed as being included in the scope of the present invention.

100: electric thrower
110: cradle
120: multi-nozzle
121: nozzle tip
130: collector

Claims (2)

A first step of dissolving polycaprolactone in two or more organic solvents to prepare a polycaprolactone solution having a concentration of 6 to 14 wt%; and
A second step of producing a nanosheet while discharging the polycaprolactone solution in the form of a filament by electrospinning;
The second step is
The polycaprolactone solution was electrospun upward from the multi-nozzle, and a voltage of 10 to 50 kV was applied at a flow rate of 200 to 800 μl/min by adjusting the TCD (tip to collector distance) to 250 to 350 mm to continuously electrically Method of manufacturing a medical nanosheet using polycaprolactone, characterized in that spinning. Medical nanosheets, characterized in that produced by the method of claim 1.

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