TWI701364B - Natural polymeric nanofiber and manufacturing method thereof - Google Patents

Abstract

The present invention provides a natural polymeric nanofibers, which is made by a natural polymeric solution under an applied field control spinning process, wherein the natural polymeric solution comprises: a natural polymeric material, an inorganic salt and/or an enzyme; the present invention further provides a method for preparing the natural polymeric nanofibers. The nature polymeric nanofibers of the present invention have a smaller fiber diameter, and have higher safety and practicability.

Description

Natural polymer nanofiber and its manufacturing method

The present invention relates to a nanofiber and its manufacturing method, in particular to a natural polymer nanofiber material and its manufacturing method.

Nanofibers are fibers with a nanometer size, and their fiber fineness ranges from tens to hundreds of nanometers, and their size can be adjusted according to different manufacturing methods. Due to the high surface area of nanofibers and the low pore size distribution and high porosity of the nets, the applications in biomedical applications are gradually growing. Currently commonly used nanofibers are made by electrospinning technology.

Electrospinning technology is a method that uses high-voltage static electricity to prepare polymer solutions into micron or nanometer fibers. The materials used in traditional electrospinning technology are all artificial polymers and organic solvents. In recent years, through the modification of natural polymers and the improvement of electrospinning equipment, the preparation of natural polymers as substrates has Nanofiber materials with special structures. However, the above-mentioned natural polymer nanofibers still need to be chemically modified to achieve the purpose. This will cause structural characteristics of natural polymers, such as proteins, etc. Changes have greatly restricted the use of industrial, medical, food, and traditional processing. Especially in the food and medical industries, organic solvents, denatured and deteriorated polymers or proteins are not available. Therefore, it is necessary to develop without using organic Solvent or physical and chemical modification can be used for nano-spinning natural polymer nanofibers.

In order to solve the above-mentioned problems, the present invention provides a natural polymer nanofiber, which is produced by a natural polymer solution in an applied field force-regulated spinning process, wherein the natural polymer solution includes: a natural polymer material , An inorganic salt, and/or an enzyme enzyme.

In a preferred embodiment, the natural polymer material is selected from but not limited to the group consisting of: gelatin (gelatin), collagen (collagen), hyaluronic acid (hyaluronic acid), alginic acid (alginate), chitosan (chitosan).

In a preferred embodiment, the inorganic salt is selected from but not limited to the group consisting of: hydroxyapatite (Hap), tricalcium phosphate (TCP), dicalcium phosphate (dicalcium phosphate, DCP), dicalcium phosphate dehydrate (DCPD), tetracalcium phosphate (TTCP), carbonate, nitrate, sulfate, calcium salt, potassium salt, sodium salt, magnesium salt.

In a preferred embodiment, the enzyme system is selected from the group consisting of but not limited to: transglutaminase, Lipase, Peptidases, Sortase ), Oxidoreductases, Tyrosinase, Polyphenoloxidase (PPO), Laccase, Peroxidase, Lysyl oxidase ) Or amine oxidases.

In a preferred embodiment, the applied field force is selected from the following group but not limited to electric field, magnetic field or gravity.

In a preferred embodiment, the average fineness of the nanofiber is 10 nm to 900 nm.

In a preferred embodiment, the natural polymer material of the natural polymer solution The material is 0.01%(W/V)~100%(W/V).

In a preferred embodiment, the inorganic salt of the natural polymer solution accounts for 0.01% (W/V) to 100% (W/V).

Another aspect of the present invention provides a method for manufacturing natural polymer nanofibers, which comprises: (a) providing a natural polymer solution, the natural polymer solution comprising: a natural polymer material, an inorganic salt, and / Or an enzyme; (b) applying a field force spinning process to the natural polymer solution to obtain the natural polymer nanofiber.

In a preferred embodiment, the natural polymer material in the method is selected from the group consisting of: gelatin, collagen, hyaluronic acid, alginic acid ( alginate), chitosan (chitosan).

In a preferred embodiment, the inorganic salt in the method is selected from the group consisting of: hydroxyapatite (Hap), tricalcium phosphate (TCP), dicalcium phosphate (dicalcium phosphate, DCP), dicalcium phosphate dehydrate (DCPD), tetracalcium phosphate (TTCP), carbonate, nitrate, sulfate, calcium salt, potassium salt, sodium salt, magnesium salt.

In a preferred embodiment, the enzyme in the method is transglutaminase.

In a preferred embodiment, the applied field forces in the method are electric field, magnetic field, and gravity.

In a preferred embodiment, the method further comprises: (c) contacting the natural polymer nanofibers with an enzyme for external cross-linking.

Another aspect of the present invention is to provide a use of natural polymer nanofibers, which Department as a biomedical material.

Compared with the prior art, the present invention can form nanofibers with uniform fiber fineness and morphology without changing the physical and chemical properties of natural polymer materials and without using organic solvents. Since artificial polymers and organic solvents are not used, the safety is greatly improved, and the application level is wider, especially in the food and biomedical industries.

Figure 1 is a photograph of the natural polymer nanofibers prepared in Example 1 of this case.

Figure 2 is a photo of the natural polymer nanofibers prepared in Example 2 of this case.

Figure 3 is a photograph of the natural polymer nanofibers prepared in Example 3 of this case.

Figure 4 is a photograph of the natural polymer nanofibers prepared in Example 4 of this case.

Figure 5 is a photograph of the natural polymer nanofibers prepared in Example 5 of this case.

Figure 6 is a photograph of the natural polymer nanofibers prepared in Example 6 of this case.

Unless otherwise defined, all technical and scientific terms herein have the same meaning as understood by those with ordinary knowledge in the field to which the present invention belongs. As used in this application, the following terms have the following meanings.

Unless otherwise specified in the context, the singular forms of "one", "one", "one" and "the" described in this document and the scope of the patent application include plural references. The terms used in this article such as: "one", "the", "one or more", "plural" and "at least one" can be substituted for each other.

The "include", "include", "include", "include" and "have" mentioned in this article can also be substituted for each other without restriction.

In addition, the "and/or" and "and/or" mentioned in this article are used as specific expressions One or all of two specific features or compositions. Therefore, the term "and/or" is used to express sentences such as "A and/or B" that include "A and B", "A or B", "(alone) A", and "(alone) B". Similarly, the term "and/or" is used to express that a sentence such as "A, B and/or C" contains the meanings described later: A, B and C; A, B or C; A or C; A Or B; B or C; A and C; A and B; B and C; (alone) A; (alone) B; (alone) C.

The natural polymer nanofiber of the present invention is prepared from a natural polymer solution using an applied field force to control the spinning process, wherein the natural polymer solution includes: a natural polymer material, an inorganic salt, And/or an enzyme enzyme.

The term "natural polymer materials" as used herein refers to polymers that exist in nature but not artificially synthesized, such as gelatin, collagen, hyaluronic acid, alginic acid, chitosan, and derivatives of the natural polymers But not limited to this; in a preferred embodiment, the weight average molecular weight of the natural polymer material is between 10,000 and 200,000, preferably between 15,000 and 150,000, and more preferably It is between 20,000 and 100,000.

The natural polymer solution referred to herein is to dissolve the above-mentioned natural polymer material in a solvent, and the solvent can be any polar solvent. In a preferred embodiment, the polar solvent is water. The natural polymer material of the natural polymer solution is 0.1%(W/V)~50%(W/V), preferably about 0.5%(W/V)~40%(W/V), more It is preferably 1%(W/V)~30%(W/V), such as 10%(W/V), 15%(W/V), 20%(W/V).

The natural polymer solution referred to herein further includes inorganic salts. The inorganic salts referred to herein are inorganic salts that can change the electrical acceptability of natural polymer materials, such as, but not limited to, hydroxylapatite, tricalcium phosphate, dicalcium phosphate, dicalcium phosphate dihydrate, phosphoric acid Tetracalcium, carbonate, nitrate, sulfate, calcium salt, potassium salt, sodium salt, magnesium salt. The natural polymer solution The inorganic salt is 0.1%(W/V)~50%(W/V), preferably about 0.5%(W/V)~40%(W/V), more preferably 1%(W/V) /V)~30%(W/V), such as 10%(W/V), 15%(W/V), 20%(W/V).

The natural polymer materials and inorganic salts in the natural polymer solution are mixed for 1 to 96 hours, preferably about 12 to 48 hours, more preferably about 24 to 36 hours, such as 24 hours, 26 hours, 28 Hours, 30 hours, 32 hours, 34 hours, 36 hours. The natural polymer solution referred to herein may contain an enzyme enzyme or not. In a preferred embodiment, the natural polymer solution contains enzymatic enzyme, and the enzymatic enzyme can internally cross-link the natural polymer to increase the strength of the prepared natural polymer nanofiber. Enzymes that can be used are preferably, but not limited to, transglutaminase, Lipase, Peptidases, Sortase, Oxidoreductases, Tyrosinase ( Tyrosinase, polyphenoloxidase (PPO), laccase, peroxidase, lysyl oxidase, amine oxidases, available concentrations Between 1% and 100%.

The method for preparing natural polymer nanofibers of the present invention is to (a) provide a natural polymer solution, the natural polymer solution comprising: a natural polymer material, an inorganic salt, and/or an enzyme; (b) ) Applying an applied field force spinning process to the natural polymer solution to obtain the natural polymer nanofiber.

The "applied field force spinning process" referred to in the preparation method of the present invention means that the natural polymer solution is loaded into a spinning device, a spinning process is performed, and the applied field force is applied during the process, including but not Limited to electric field, magnetic field, and gravity, it drives the anions and cations of the natural polymer solution, and in turn drives the natural polymer materials to form nanofibers. According to a preferred embodiment of the present invention, The applied field force spinning process is an electric discharge spinning process, and has an applied voltage ranging from 1 microvolt to 1000 kV, preferably 1 kV to 70 kV, more preferably 30 kV Volts to 50 kilovolts. In addition, the distance from the spinning nozzle to the collection area of the discharge spinning process is between 1 to 30 cm, and the discharge speed of the discharge spinning process can be no less than 10 μl/min.

The preparation method of the present invention may further include an external cross-linking step, that is, cross-linking the natural polymer nanofibers obtained above in contact with an enzyme cross-linking agent to increase the strength of the natural polymer nanofibers and prolong the degradation time. The crosslinking time can be 1 to 96 hours, preferably about 24 to 48 hours, such as 24 hours, 26 hours, 28 hours, 30 hours, 32 hours, 34 hours, 36 hours, 38 hours, 40 hours, 42 hours , 44 hours, 46 hours, 48 hours, etc. The above-mentioned "contact" refers to any method that can interact the enzyme crosslinking agent with natural polymer nanofibers, such as immersing the natural polymer nanofibers in the enzyme crosslinking agent, or spraying the enzyme crosslinking agent on the natural polymer nanofibers. Polymer nanofibers, but not limited to the above methods.

The natural polymer nanomaterial prepared by the above method, wherein the average fineness of the nanofiber is 10nm to 500nm, preferably 10nm to 50nm, such as 10nm, 20nm, 30nm, 40nm, 50nm, etc. Since the natural polymer nanofibers of the present invention have better fineness and improved safety, compared with artificial polymer nanofibers, the present invention has a wider range of polymer nanofibers. It is used in food, biomedicine and other categories, such as nanofiber materials that can be used for three-dimensional printing in biomedicine.

In order to enable anyone who is familiar with the relevant art to understand the technical content of the present invention and implement it accordingly, and according to the content disclosed in this specification, the scope of patent application and the drawings, anyone who is familiar with the relevant art can easily understand the purpose and advantages of the present invention. Therefore, the detailed features and advantages of the present invention will be described in detail in the embodiments. The following examples are only for illustration, not for limiting the The scope of patent application for the case.

[Example 1]

Prepare 20% (w/v) gelatin (gelatin) aqueous solution, and add 20% (w/v) hydroxide apatite to the gelatin aqueous solution, continue to mix and stir for 24 hours; then, control the temperature at 50℃± At 5°C, put it into a 10mL syringe, the drawing height is 60mm, the injection speed is 2mL/hr, and the electric field voltage is 20kV. The obtained natural polymer nanofibers are shown in Figure 1.

[Example 2]

The same formula is used as in Example 1, the difference is that 10wt% of enzyme crosslinking agent is added, and the other methods are the same; the obtained natural polymer nanofiber is shown in Figure 2.

[Example 3]

The difference between this example and example 1 is that 20% (w/v) hydroxide apatite is replaced with tricalcium phosphate (TCP), and the rest is the same. The obtained natural polymer nanofiber is shown in Figure 3. Shown.

[Example 4]

The difference between this example and example 3 is that 10wt% of enzyme crosslinking agent is added, the injection speed is adjusted to 1.3mL/hr, the electric field voltage is 13.5kV, and the other methods are the same. The obtained natural polymer nanofibers are as in the fourth As shown in the figure.

[Example 5]

Prepare 5% (w/v) gelatin (gelatin) aqueous solution, and add 5% (w/v) tricalcium phosphate to the gelatin aqueous solution, continue to mix and stir for 24 hours; then, control the temperature at 50℃±5℃ , Put into 10mL syringe, draw wire height 60mm, injection speed 0.9mL/hr, electric field voltage 7kV. The obtained natural polymer nanofibers are shown in Figure 5.

[Example 6]

The difference between this embodiment and the embodiment 5 is that 10wt% of the enzyme crosslinking agent is added, and the other methods are the same. The obtained natural polymer nanofiber is shown in Figure 6.

The above-mentioned embodiments are used to illustrate the characteristics of the present invention, and their purpose is to enable those familiar with the technology to understand the content of the present invention and implement them accordingly, rather than limiting the patent scope of the present invention, so everything else does not deviate from the disclosure of the present invention. Equivalent modifications or amendments completed in the spirit of the above should still be included in the scope of patent application described below.

Claims (9)

A natural polymer nanofiber is prepared by using a natural polymer solution in an applied field force-regulated spinning process, wherein the natural polymer solution includes: a natural polymer material, an inorganic salt, and a Enzyme enzyme as the internal crosslinking agent of the natural polymer material; wherein the natural polymer material of the natural polymer solution is 0.5% (W/V) ~ 50% (W/V), and the inorganic salt is 0.5% (W/V)~50%(W/V); where the applied field force is an electric field, a magnetic field or gravity; where the enzyme enzyme is transglutaminase. The natural polymer nanofiber of claim 1, wherein the natural polymer material is selected from the group consisting of: gelatin, collagen, hyaluronic acid, alginic acid (alginate), chitosan (chitosan). Such as the natural polymer nanofiber of claim 1, wherein the inorganic salt is selected from the group consisting of: hydroxyapatite (Hap), tricalcium phosphate (TCP), dicalcium phosphate (dicalcium phosphate, DCP), dicalcium phosphate dehydrate (DCPD), tetracalcium phosphate (TTCP), carbonate, nitrate, sulfate, calcium salt, potassium salt, sodium salt, magnesium salt. The natural polymer nanofiber of claim 1, wherein the average fineness of the nanofiber is 10nm to 900nm. A method for manufacturing natural polymer nanofibers, comprising: (a) providing a natural polymer solution, the natural polymer solution comprising: a natural polymer material, an inorganic salt, and a natural polymer material Enzyme enzyme of internal cross-linking agent; (b) applying an applied field force spinning process to the natural polymer solution to obtain the natural polymer nanofiber; wherein the applied field force is an electric field, a magnetic field, or gravity; The enzyme enzyme is transglutaminase. Such as the manufacturing method of claim 5, wherein the natural polymer material is selected from the group consisting of: gelatin (gelatin), collagen (collagen), hyaluronic acid (hyaluronic acid), alginate (alginate), Chitosan (chitosan). Such as the manufacturing method of claim 5, wherein the inorganic salt is selected from the group consisting of: hydroxylapatite (Hap), tricalcium phosphate (TCP), dicalcium phosphate (dicalcium phosphate, DCP), dicalcium phosphate dehydrate (DCPD), tetracalcium phosphate (TTCP), carbonate, nitrate, sulfate, calcium salt, potassium salt, sodium salt, magnesium salt. The manufacturing method according to any one of claims 5 to 7, further comprising: (c) contacting the natural polymer nanofiber with an enzyme to perform external crosslinking. A use of the natural polymer nanofiber according to any one of claims 1 to 4, which is used as a biomedical material.

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