TWI586384B - Preparation method of conformal nanofiber wound dressing - Google Patents

Description

Method for manufacturing directional nanofiber wound dressing material

The invention relates to a method for manufacturing a dressing material, in particular to a method for manufacturing a directional nanofiber wound dressing material, which comprises a nanofiber wound with anti-inflammatory, good affinity for growth factors and promoting wound healing. Dressing.

When the skin is seriously damaged, the wound dressing can replace the original function of the skin, so as to avoid infection, dehydration, and even promote wound healing, reduce pain, and reduce the formation of scars after healing. The conventional nanofiber dressings are irregularly arranged, which is not conducive to the migration of the epidermal cells and vascular endothelial cells of the user to the wound site, and the wound healing ability is greatly reduced.

Therefore, in view of the problems existing in the above-mentioned conventional nanofibers, how to develop an innovative nanofiber dressing material with more ideal and practicality is really eagerly awaited by consumers, and it is also necessary for related industries to make efforts to develop breakthroughs. Goals and directions.

The invention relates to a method for manufacturing a directional nanofiber wound dressing, comprising the steps of: preparing a polymer: the high molecular polymer and the curcumin powder are dissolved in a mixed solvent of dimethylformamide and tetrahydrofuran to form a high. Molecular solution; electrospinning step: forming the above polymer solution into a thin nanofiber by an electrospinning device Membrane, and then using a high-speed roller to prepare a forward-looking polymer nanofiber membrane containing curcumin; surface modification step: heparin is grafted onto the surface of the directional polymer nanofiber membrane containing curcumin.

Among them, the forward-looking polymer nanofiber film containing curcumin produced in the electrospinning step was placed in an oven at 37 ° C for drying.

Wherein, the surface modification step is to insert a forward-looking polymer nanofiber membrane containing curcumin into a DC plasma reactor, and a vacuum plasma reactor is evacuated to 30 mtorr, and then high-purity oxygen is introduced to maintain the pressure at 200 mottor. The 600v voltage input generates a gas plasma, and the gas plasma treats the forward-looking polymer nanofiber membrane containing curcumin for 60 seconds; then, the directional macromolecular nanofiber membrane containing curcumin is immersed in 1-B. Poly-3-(3-dimethylaminopropyl)carbonyldiimide (EDC) and N-hydroxysuccinimide (NHS) in a 2-morpholine ethanesulfonic acid buffer solution with its internal configuration After the crosslinking reaction of poly(ethylene glycol) diamine (PEG-di-amine) at room temperature for twenty-four hours, the surface grafting of the first stage is completed. At this time, the electrospun fiber membrane is called an amine. Poly(lactic-co-glycolic acid/curcumin-NH ₂ nanofibrous membrane referred to as PC-NH ₂ ; subsequent second stage surface grafting, amine group Polylactic acid-polyglycolic acid/curcumin nanofiber membrane (PC-NH ₂ ) immersed in EDC and NHS containing 2 - in the morpholine ethanesulfonic acid buffer solution, the heparin disposed inside is reacted with the internally disposed heparin at room temperature for twenty-four hours, thereby obtaining heparin grafted onto the surface of the directional polymer nanofiber membrane containing curcumin. The electrospun fiber membrane at this time is called poly(lactic-co-glycolic acid/curcumin/heparin nanofibrous membrane abbreviated as PCH).

In the above, the pH of the 2-morpholine ethanesulfonic acid buffer solution was pH=7.

In the above, 15 nmole of polyethylene diamine was added per 1 mg of the polylactic acid-polyglycolic acid/curcumin film, and 12.5 nmole of heparin was added per 1 mg of the polylactic acid-polyglycolic acid/curcumin-NH ₂ film.

Among them, the high molecular polymer is a polylactic acid-polyglycolic acid, a natural polymer or a polymer produced by electrospinning.

Among them, the ratio of the polymer polylactic acid-polyglycolic acid powder to the curcumin powder is 20:1.

Among them, the mixed solvent ratio of dimethylformamide to tetrahydrofuran is 1:1.

In the above, the polymer polylactic acid-polyglycolic acid powder mixed curcumin powder accounts for 27.3% of the polymer solution, and the mixed solvent of dimethylformamide and tetrahydrofuran accounts for 72.7% of the polymer solution.

The invention has the advantages that the high-speed roller is used to collect the directional nanofiber membrane, and the synthetic high molecular weight polylactic-co-glycclic acid (PLGA) is used as the main material, and the antioxidant is added. The anti-inflammatory curcumin is grafted on the surface of the electrospun fiber membrane to immobilize heparin with good affinity to various growth factors, by means of the material's directional fiber structure, the action of curcumin and heparin, and the intercellular The interaction, a nanofiber film electrospinning material that promotes wound healing, reduces scarring, and rebuilds the skin.

The above described objects, structures, and features of the present invention will be apparent from the following description of the preferred embodiments of the invention.

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Figure 1 is a block diagram showing the preparation process of the present invention.

Figure 2 is a schematic diagram of a scanning electron microscope of PLGA, PC and PCH forward nanofiber film of the present invention (scale bar: 10 μm)

Figure 3 is a schematic view of a scanning electron microscope of a PC, PC-plasma, PC-NH ₂ , and PCH directional nanofiber film of the present invention (scale bar: 300 nm)

Figure 4 is a schematic view of the comparison of the different dressings of the present invention for the healing area of rat skin wounds

Referring to Figures 1 to 4, the present invention is a method for manufacturing a directional nanofiber wound dressing material. The materials and arrangement methods in this experiment are as follows:

Solution preparation step (step 101): taking 2.6 g of high molecular polylactic acid-polyglycolic acid powder as main body and 0.13 g of curcumin powder dissolved in a mixed solvent of 7.27 g of dimethylformamide and tetrahydrofuran to form a polymer solution The mixed solvent ratio of dimethylformamide to tetrahydrofuran is 1:1.

Electrospinning step (step 102): injecting a uniformly mixed polymer solution into a 10 ml plastic syringe, using an electrospinning electric field voltage of 20 kV, a spun to a collector distance of 10 cm, and a collector rotation speed of 3500 rpm. Under the conditions of the strip, a polylactic acid polyglycolic acid mixed curcumin nanofiber with a diameter ranging from 456 to 479 nm and an electrospinning vertical angle of 89.6-90.5° can be spun, and a curcumin-containing cis is prepared using a high-speed roller. The polylactic acid-polyglycolic acid nanofiber film (PC) was placed, and the above-mentioned curative nanofiber film containing curcumin was placed in an oven at 37 ° C for drying and stored in a moisture-proof box.

Surface modification step (step 103): using 1-ethyl-3-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC)/N- N-hydroxysuccinimide (NHS) is used as a cross-linking agent for PEG-di-amine and heparin, and buffered with 0.5M 2-morpholine ethanesulfonic acid. The solution (2-(N-morpholino) ethanesulfonic acid buffer, MES buffer) is used as a solvent for crosslinking; Step 1: Surface chemical grafting The first stage is PEG-di-amine and PC electrospinning after oxygen plasma treatment. PC-plasma, which is a polylactic acid-polyglycolic acid nanofiber film placed in a DC filter reactor. The DC plasma reactor is evacuated to 30 mtorr and then passed through high-purity oxygen. Maintaining at 200mtorr, setting a voltage input of 600v to generate a gas plasma, the gas plasma is processed for the polylactic acid-polyglycolic acid nanofiber film for 60 seconds, firstly MES buffer having a pH of 6 and a pH of 0.5M is disposed. And add 1g of EDC and 0.5g of NHS per 1mL of MES buffer as cross-linking solvent, per 1mg of polylactic acid-polyglycolic acid/curcumin Add 15nmole of polyethylene bisamine 0.052mg, put 50ml of cross-linking solution into the beaker, and cross-link the 50mg electrospun fiber membrane into the cross-linking solution for 24 hours at room temperature. After the reaction, the material is taken out and washed several times with water, and the electrospun fiber membrane after the first stage grafting is called an amino-based polylactic acid-polyglycolic acid/curcumin fiber membrane (poly(lactic- Co-glycolic acid)/curcumin-NH ₂ nanofibrous membrane (PC-NH ₂ ); Step 2: Surface chemical grafting The second stage is heparin and PC-NH ₂ , and the MES buffer with pH 70.5M is placed, and every 1 mL Add 1g of EDC and 0.5g of NHS as cross-linking solvent to the MES buffer, add 12.5nmole of heparin 0.125mg per 1mg of polylactic acid-polyglycolic acid/curcumin-NH ₂ film, and crosslink the configured 50ml. The solution was placed in a beaker, and 50 mg of the electrospun fiber membrane was poured into the cross-linking solution to carry out a cross-linking reaction at room temperature for twenty-four hours. After the reaction, the material was taken out and washed with water once several times, and the second stage was taken. The electrospun fiber membrane behind the branch is called polylactic acid-polyglycolic acid/curcumin/heparin nanofiber membrane (poly(lactic-c) O-glycolic acid)/curcumin/heparin nanofibrous membrane (PCH); cross-linking the surface of the nanofiber membrane with heparin to graft heparin onto the surface of the directional polymer nanofiber membrane containing curcumin.

In the above, the polymer polylactic acid-polyglycolic acid powder mixed curcumin powder accounts for 27.3% of the polymer solution, and the mixed solvent of dimethylformamide and tetrahydrofuran accounts for 72.7% of the polymer solution.

Referring to Figure 4, three types of nanofiber membranes (PLGA, PC, PCH) were used in the dorsal cortical trauma test of diabetic rats, and gauze was used as a negative control group. After 14 days of wound healing, PCH had a 86% wound repair rate, which was statistically significantly different from other groups.

It is known from the results that the present invention uses a polymer polylactic acid-polyglycolic acid as a main material, and adds curcumin having anti-oxidation and anti-inflammatory effects, and prepares a forward nanofiber film by electrospinning, and then fixes it. A method of grafting heparin with good affinity to various growth factors on the surface of an electrospun fiber membrane to produce a nanofiber wound dressing PCH having anti-inflammatory, good affinity for growth factors and promoting wound healing, is a skin Rebuild the best dressing.

The foregoing description of the preferred embodiments of the present invention is intended to be illustrative of the embodiments of the invention, and the invention may be modified and modified without departing from the spirit and scope of the invention. Such changes and modifications are to be covered by the scope of the following patent application.

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Claims (5)

A method for manufacturing a directional nanofiber wound dressing, comprising the steps of: preparing a polymer solution by dissolving a polymer and a curcumin powder in a mixed solvent of dimethylformamide and tetrahydrofuran to form a polymer solution; The high molecular polymer is polylactic acid-polyglycolic acid, and the ratio of the polymer polylactic acid-polyglycolic acid powder to the curcumin powder is 20:1; the mixed solvent ratio of dimethylformamide to tetrahydrofuran is 1:1. The polymer polylactic acid-polyglycolic acid powder mixed curcumin powder accounts for 27.3% of the polymer solution, and the mixed solvent of dimethylformamide and tetrahydrofuran accounts for 72.7% of the polymer solution; electrospinning Step: using the high-speed roller of the electrospinning device to form the polymer solution into a forward-looking polymer nanofiber membrane containing curcumin; surface modification step: heparin grafting to a cis-polymeric naphthalene containing curcumin Rice fiber membrane surface. The method for producing a directional nanofiber wound dressing according to the first aspect of the invention, wherein the curative polymer nanofiber film containing curcumin produced in the electrospinning step is placed in 37 Dry in a °C oven. The method for producing a directional nanofiber wound dressing according to the first aspect of the invention, wherein the surface modification step is to insert a forward-looking polymer nanofiber film containing curcumin into a DC plasma reactor, The DC plasma reactor is vacuumed at 30mtorr, then high-purity oxygen is introduced, the pressure is maintained at 200 mottor, 600v voltage input is set to generate gas plasma, and the gas plasma treats the forward-looking polymer nanofiber membrane containing curcumin for 60 seconds. Then, the directional macromolecular nanofiber membrane containing curcumin is immersed in 1-ethyl-3-(3-dimethylaminopropyl)carbonyldiimide (EDC) and N-hydroxysuccinimide (NHS) in a 2-morpholine ethanesulfonic acid buffer solution and a polyethylene bisamine internally disposed therein for crosslinking reaction at room temperature for twenty-four hours, completing the first One-stage surface grafting, at this time, the electrospun fiber membrane is called an amine-based polylactic acid-polyglycolic acid/curcumin nanofiber membrane; the second stage of surface grafting, the amine-based polylactic acid-polygan The alkyd/curcumin fiber membrane is immersed in a 2-morpholine ethanesulfonic acid buffer solution containing EDC and NHS, and the heparin disposed therein is cross-linked at room temperature for twenty-four hours to obtain heparin grafting. The surface of the directional polymer nanofiber membrane of curcumin, the electrospun fiber membrane at this time is called polylactic acid-polyglycolic acid/curcumin/heparin nanofiber membrane. The method for producing a directional nanofiber wound dressing according to claim 3, wherein 15 mg of polyethylene bisamine is added per 1 mg of the polylactic acid-polyglycolic acid/curcumin film, per 1 mg. The polylactic acid-polyglycolic acid/curcumin-NH ₂ membrane was added with 12.5 nmole of heparin. The method for producing a directional nanofiber wound dressing according to claim 3, wherein the pH of the 2-morpholine ethanesulfonic acid buffer solution is pH=7.