JP7121944B2 - Nanofiber and its manufacturing method - Google Patents

Description

The present invention relates to nanofibers composed of biodegradable polyesters and methods of making the same.

In recent years, there have been concerns that plastic waste is causing a great burden on the global environment, such as the impact on ecosystems, the generation of toxic gases when burned, and global warming due to the large amount of heat generated by combustion. The development of biodegradable plastics is gaining momentum as plastics that can solve the above problems.

Recently, from the viewpoint of biodegradability and carbon neutrality, attention has been paid to aliphatic polyester resins as biodegradable plastics. Among them, polyhydroxyalkanoate (hereinafter sometimes abbreviated as PHA), particularly poly(3-hydroxybutyrate) homopolymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) ) copolymer, poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) copolymer (hereinafter sometimes referred to as PHBH), poly (3-hydroxybutyrate-co-4-hydroxybutyrate Late) copolymers, polylactic acid, etc. are attracting attention.

Such polyester resins are biodegradable, have excellent biocompatibility, and are non-toxic to the human body. Therefore, it is being studied to form nanofibers from this and apply the nanofibers to biomedical applications as wound dressings and scaffolds used in tissue engineering and the like. Known methods for forming such nanofibers include melt spinning and electrospinning.

Patent Literature 1 describes forming a biodegradable polyester porous fiber by a melt spinning method and encapsulating (specifically, impregnating) a functional drug in the porous fiber.

Non-Patent Document 1 reports nanofibers composed of 70% by weight of poly(3-hydroxybutyrate), 30% by weight of polyethylene glycol, and caffeic acid, which is a natural phenol.

JP 2012-246588 A

Materials Science and Engineering C 65, 2016, p. 379-392

The invention described in Patent Document 1 impregnates the porous fiber with the functional agent without mixing the functional agent into the porous fiber, so the content of the agent in the porous fiber is limited. rice field. In addition, Non-Patent Document 1 does not describe the inclusion of natural substances other than caffeic acid, and it was necessary to use polyethylene glycol in addition to poly(3-hydroxybutyrate).

An object of the present invention is to provide a novel nanofiber in which an anti-inflammatory agent is mixed with biodegradable polyester, which is the main raw material.

The present invention relates to nanofibers comprising a mixture of biodegradable polyester and at least one anti-inflammatory agent selected from the group consisting of emu oil, centella asiatica, and propolis. Preferably, said biodegradable polyester is a polyhydroxyalkanoate, more preferably poly(3-hydroxybutyrate), poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3- at least one selected from the group consisting of hydroxybutyrate-co-3-hydroxyhexanoate) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate). Preferably, the content of the anti-inflammatory agent is 10 to 30 parts by weight with respect to 100 parts by weight of the biodegradable polyester.

The present invention also relates to a method of making nanofibers comprising electrospinning a solution comprising biodegradable polyester and emu oil.

Further, the present invention also relates to a method for producing nanofibers, comprising mixing a solution of Centella asiatica in a polar solvent and a solution of a biodegradable polyester, and electrospinning the resulting mixed solution. Furthermore, the present invention also relates to a method for producing nanofibers, comprising mixing a polar solvent solution of propolis and a solution of biodegradable polyester, and electrospinning the resulting mixed solution. Preferably, said polar solvent is acetone or ethanol.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a novel nanofiber in which an anti-inflammatory agent is mixed with biodegradable polyester, which is the main raw material.

Electron micrograph of Centella Asiatica-containing nanofibers produced in Example 1 Electron micrograph of Centella Asiatica-containing nanofibers produced in Example 2 Electron micrograph of Centella Asiatica-containing nanofibers produced in Example 3 Electron micrograph of Centella Asiatica-containing nanofibers produced in Example 4 Electron micrograph of Centella Asiatica-containing nanofibers produced in Example 5 Electron micrograph of Centella Asiatica-containing nanofibers produced in Example 6 Electron micrograph of Centella Asiatica-containing nanofibers produced in Example 7 Electron micrograph of Centella Asiatica-containing nanofibers produced in Example 8 Electron micrograph of Centella Asiatica-containing nanofibers produced in Example 9 Electron micrograph of emu oil-containing nanofibers produced in Example 12 Electron micrograph of emu oil-containing nanofibers produced in Example 13 Electron micrograph of emu oil-containing nanofibers produced in Example 14 Electron micrograph of propolis-containing nanofibers produced in Example 20 Electron micrograph of propolis-containing nanofibers produced in Example 21 Electron micrograph of propolis-containing nanofibers produced in Example 22 Electron micrograph of propolis-containing nanofibers produced in Example 23 Electron micrograph of propolis-containing nanofibers produced in Example 24 Electron micrograph of propolis-containing nanofibers produced in Example 25

Embodiments of the present invention are described in detail below.
The present invention relates to nanofibers comprising a mixture of biodegradable polyester and at least one anti-inflammatory agent selected from the group consisting of emu oil, centella asiatica, and propolis. This configuration allows the nanofibers of the present invention to have anti-inflammatory properties in addition to being biodegradable and biocompatible.

[Biodegradable Polyester]
The biodegradable polyester used in the present invention is not particularly limited, but examples thereof include polyhydroxyalkanoate (hereinafter abbreviated as PHA), polyalkylenedicarboxylate, polybutylene adipate-co-terephthalate and the like. Only one type of biodegradable polyester may be used, or multiple types may be used in combination. Among these, PHA is preferable.

The PHA refers to a polyester having hydroxyalkanoic acid as a monomer unit. Specific examples include polyglycolic acid, polylactic acid, poly-3-hydroxyalkanoate (hereinafter abbreviated as P3HA), poly-4-hydroxyalkanoate and the like. Among these, PLA and P3HA are preferred, and P3HA is more preferred.

The P3HA has the general formula (1): [-CHR-CH ₂ -CO-O-] (wherein R is an alkyl group represented by C _n H _2n+1 and n is an integer of 1 or more and 15 or less ) is a polyester containing repeating units represented by The form of copolymerization is not particularly limited, and may be random copolymerization, alternating copolymerization, block copolymerization, graft copolymerization, or the like. Random copolymerization is preferred because it is readily available. The P3HA may be a polyester copolymer containing repeating units represented by formula (1) and other repeating units.

P3HA that can be used in the present invention is not particularly limited, but examples include PHB [poly(3-hydroxybutyrate)], PHBH [poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)], poly( 3-hydroxybutyric acid-co-3-hydroxyhexanoic acid)], PHBV [poly (3-hydroxybutyrate-co-3-hydroxyvalerate), poly (3-hydroxybutyric acid-co-3-hydroxyvaleric acid)] , P3HB4HB [poly (3-hydroxybutyrate-co-4-hydroxybutyrate), poly (3-hydroxybutyrate-co-4-hydroxybutyrate)], poly (3-hydroxybutyrate-co-3-hydroxyvalerate) -co-3-hydroxyhexanoic acid), poly(3-hydroxybutyrate-co-3-hydroxyoctanoate), poly(3-hydroxybutyrate-co-3-hydroxyoctadecanoate), etc. . Among these, PHB, PHBH, PHBV, and P3HB4HB are preferable as they are industrially easy to produce. Among these copolymers, PHBH is particularly preferred. PHBH has a wide range of processing temperatures that can be applied during heat processing, so it has good processability when secondary processing a sheet made of nanofibers. This is because there is an advantage that it is easy to uniformly mix with the inflammatory agent.

The average composition ratio of repeating units in P3HA, especially PHBH, is 80 mol % to 99 mol % of 3-hydroxybutyrate repeating units from the viewpoint of the balance between flexibility and strength of the resulting nanofiber. It is preferably 85 mol % to 97 mol %, more preferably. If the composition ratio of the 3-hydroxybutyrate repeating unit is less than 80 mol %, the rigidity tends to be insufficient, and if it exceeds 99 mol %, the flexibility tends to be insufficient.

In the present invention, P3HA may be used alone or in combination of at least two or more. Specifically, two or more types of P3HA having different composition ratios of 3-hydroxybutyrate repeating units may be mixed and used.

The molecular weight of P3HA used in the present invention is not particularly limited as long as it exhibits substantially sufficient physical properties for the intended use. A low molecular weight may reduce the strength of the resulting nanofibers. Conversely, if it is too high, fiberization may become difficult. Taking these into consideration, the weight average molecular weight range of the biodegradable polyester used in the present invention is preferably 50,000 to 3,000,000, more preferably 100,000 to 1,500,000. In addition, the weight average molecular weight here refers to the one measured from the polystyrene equivalent molecular weight distribution using gel permeation chromatography (GPC) using a chloroform eluent. As the column in the GPC, a column suitable for measuring the molecular weight may be used.

P3HA is preferably produced by a microorganism, and the microorganism that produces P3HA is not particularly limited as long as it has the ability to produce P3HA. Examples of hydroxybutyrate and other hydroxyalkanoate copolymer-producing bacteria include Aeromonas caviae, which is a PHBV and PHBH-producing bacterium, and Alcaligenes eutrophus, which is a P3HB4HB-producing bacterium. Are known. In particular, with regard to PHBH, Alcaligenes eutrophus AC32 strain (Alcaligenes eutrophus AC32, FERM BP-6038) (T.Fukui, Y.Doi, J.Bateriol) into which a PHA synthase group gene was introduced in order to increase the productivity of PHBH. ., 179, p4821-4830 (1997)) and the like are more preferable. In addition to the above, genetically modified microorganisms into which various PHA synthesis-related genes have been introduced can be used according to the P3HA to be produced.

After culturing these microorganisms under appropriate conditions to accumulate P3HA in the cells, the cells can be disrupted to isolate P3HA.

[Anti-inflammatory agent]
The nanofiber of the present invention contains at least one selected from the group consisting of emu oil, centella asiatica, and propolis as an anti-inflammatory agent.

Centella asiatica (also known as Centella asiatica) is a plant belonging to the Umbelliferae family that grows in tropical wetlands such as Indonesia, Malaysia, and India. It is also called Gotu Kola. It is known to have various medicinal effects, for example, it is effective in wound healing, has a higher ability to promote collagen synthesis than vitamin C, has a better lipolytic activity than caffeine, and is equivalent to grape seed extract. is known to have an inhibitory effect on the free radical scavenging activity of In addition, it is known to have antibacterial, antiseptic and anti-inflammatory properties, and these pharmacological effects are said to promote wound healing, treat damaged tissue, and reduce scars. Centella asiatica is mainly known to contain the following active ingredients: asiaticoside, a triterpene glycoside of antibiotics; Binder of braminoside; Madecassoside, a strong anti-inflammatory.

In the present invention, the form of Centella asiatica is not particularly limited, but it is preferable to use Centella asiatica in a dry powder form in producing nanofibers. Moreover, it is preferable that the nanofibers of the present invention contain the extract obtained by extracting the dried powder Centella asiatica using a polar solvent. This stabilizes electrospinning and enables the stable production of nanofibers composed of a mixture of biodegradable polyester and Centella asiatica. A polar solvent that can be used here will be described later.

Emu oil is an oil component collected from Emu (Dromaius novaehollandiae), a bird that originates in Australia and is classified in the genus Emu, Order Cassowary, Family Cassowary. It is mainly composed of fatty acids such as oleic acid and omega-9 fatty acids. Oleic acid is a substance that is easily absorbed through human skin, and omega-9 fatty acid is a chemical substance necessary for cell membranes as an anti-inflammatory agent, and is known to be capable of promoting wound healing.

Propolis, also called bee tar, is one of the honey-like substances produced by bees. It is made by honeybees collecting sap and pollen from the buds and bark of trees and mixing it with enzymes and beeswax found in the bee's saliva. It is said that it mainly prevents the invasion and propagation of microorganisms by applying it to the nest. Propolis is rich in vitamins such as vitamin B1, vitamin B2, and vitamin E, and minerals such as calcium and magnesium. .

The nanofibers of the present invention are composed of a mixture of biodegradable polyester and at least one anti-inflammatory agent selected from the group consisting of emu oil, centella asiatica, and propolis. This allows the anti-inflammatory agent to be evenly dispersed in the nanofibers. The nanofibers of the present invention are distinguished from nanofibers composed of biodegradable polyester impregnated with an anti-inflammatory agent.

The content of the anti-inflammatory agent in the nanofiber of the present invention is not particularly limited and can be determined as appropriate. Parts by weight is more preferred, and 10 to 30 parts by weight is even more preferred. With such a content ratio, it can be expected that the activity of the anti-inflammatory agent is exhibited while maintaining the form of the nanofibers.

The nanofibers of the present invention may contain components other than the biodegradable polyester and the anti-inflammatory agent within the range in which the effects of the present invention are exhibited. Such ingredients include other polymer ingredients, other anti-inflammatory agents; antioxidants, UV absorbers, colorants such as dyes and pigments, plasticizers, lubricants, inorganic fillers, additives such as antistatic agents. Ingredients: nucleating agents for adjusting the crystallization speed, and the like. The contents of these other components are not particularly limited as long as they do not impair the effects of the present invention.

[Nanofiber]
Nanofibers of the present invention refer to nano-sized fibers, preferably having a fiber diameter of less than 2,000 nm. Nano-sized fibers are known to be excellent in filtration performance, wiping performance, liquid retention performance, etc. due to their morphology such as large porosity and large specific surface area. The fiber diameter is more preferably less than 1500 nm, more preferably less than 1000 nm. Although the lower limit of the fiber diameter is not particularly limited, it is preferably 100 nm or more, more preferably 200 nm or more, and even more preferably 300 nm or more.

The nanofibers of the present invention can be produced by an electrospinning method, which will be described later, whereby a sheet (nonwoven fabric) made of nanofibers can be formed. Electrospun nanofibers are porous and are suitable for biocompatible, bioabsorbable, and/or anti-inflammatory wound dressings and scaffolds for tissue engineering.

By laminating a plurality of such sheets, a thick fiber laminated structure can be produced. Such a fiber laminated structure can be easily adjusted in thickness by changing the number of laminated layers, and is suitably used as a medical material having biocompatibility, bioabsorbability and/or anti-inflammatory action. be able to.

[Production method]
The nanofibers of the invention can be produced by electrospinning a solution containing a biodegradable polyester and an anti-inflammatory agent. Commercially available electrospinning equipment can be used to perform electrospinning. Electrospinning conditions are not particularly limited, and may be appropriately selected so as to obtain desired nanofibers.

As a solvent that can be used for the mixed solution, a biodegradable polyester and a solvent capable of dissolving the anti-inflammatory agent or its main component may be selected. Examples of such solvents include HFIP (formal name: 1,1,1,3,3,3-hexafluoro-2-propanol), TFE (CF ₃ CH ₂ OH), TFP (HCF ₂ CF ₂ CH _{2 OH} ), _{fluoroalcohols} such as _C6F13C2H4OH ; _dioxane ; dimethylsulfoxide; water and the like. Among these, fluoroalcohols are preferred, and HFIP is particularly preferred. One or more of these solvents may be used, or a mixture of two or more may be used in consideration of the solubility of both the biodegradable polyester and the anti-inflammatory agent or its main component.

The concentration of the solution containing the biodegradable polyester and the anti-inflammatory agent may be appropriately selected so as to enable fiberization by electrospinning. The concentration of the biodegradable polyester is preferably about 0.5 to 5 mass %, more preferably about 0.5 to 3 mass %.

In embodiments using Centella asiatica or propolis as an anti-inflammatory agent, a polar solvent solution of Centella asiatica is prepared and biodegraded with it prior to preparing the solution comprising the biodegradable polyester and the anti-inflammatory agent. Preferably, a mixed solution containing the biodegradable polyester and Centella asiatica is prepared by mixing solutions of the biodegradable polyester. The polar solvent solution of Centella asiatica is preferably prepared by mixing Centella asiatica and a polar solvent, sufficiently stirring the mixture, and then filtering to remove insoluble matter. By removing the insoluble matter in advance in this manner, the electrospinning can be performed stably.

The polar solvent used for dissolving Centella asiatica or propolis is not particularly limited, but for example, acetone, alcohols such as methanol and ethanol, and the like, which are harmless to the human body and the environment, or have a small effect. is preferred. Only one type of polar solvent may be used, or two or more types may be used in combination.

The amount of the polar solvent to be used is not particularly limited, and an amount that can sufficiently dissolve the main components of Centella asiatica or propolis may be used. For example, the weight ratio of Centella asiatica or propolis to the polar solvent is It may be about 1:1 to 100, preferably about 1:2 to 30.

EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to these examples.

(material)
PHBH: Poly-3-hydroxybutyrate-co-3-hydroxyhexanoate (3HH content 5.5%, weight average molecular weight 5.37×10 ⁵ ), Kaneka Emu Oil, Songline Enterprises Centella Asiatica powder, Songline Enterprises propolis, Stakich HFIP: 1,1,1,3,3-hexafluoro-2-propanol, Wako Pure Chemical Industries, Ltd. ethanol, Wako Pure Chemical Industries, Ltd. acetone, Wako Pure Made by Yakukogyo

(Example 1)
Centella asiatica powder and ethanol as a polar solvent were mixed at a weight ratio of 1:15 and stirred at 37° C. for 24 hours. The resulting liquid was filtered using filter paper to remove insoluble matter from the liquid to obtain a Centella asiatica solution.

Separately, PHBH and HFIP as a solvent were mixed and stirred at 37° C. for 3 hours to obtain a PHBH solution with a PHBH concentration of 1% by weight.

The Centella asiatica solution and the PHBH solution were mixed and stirred at 37° C. for 1 hour to obtain a mixed solution containing 10 parts by weight of Centella asiatica with respect to 100 parts by weight of PHBH.

Next, using a nanofiber electrospinning unit manufactured by Kato Tech Co., Ltd., the mixed solution was electrospun to prepare a nanofiber sheet composed of a mixture of PHBH and Centella asiatica. The electrospinning conditions were temperature 23° C., humidity 30% RH, injection angle 30°, flow rate 100 L/min, applied voltage 15-20 kV, and syringe pump speed 0.2 mm/min.

The resulting nanofibers were photographed with a scanning electron microscope (JSM-6010LA, manufactured by JEOL Ltd.). Photographs taken are shown in FIG. From the obtained micrograph, the fiber diameter was measured at 100 points using image analysis software, and the average value was defined as the diameter of the nanofiber.

(Example 2)
A nanofiber sheet was produced in the same manner as in Example 1, except that the ratio of Centella asiatica to 100 parts by weight of PHBH in the mixed solution was changed to 20 parts by weight. A photograph of the nanofibers is shown in FIG. The diameters of the nanofibers obtained are shown in Table 1.

(Example 3)
A nanofiber sheet was produced in the same manner as in Example 1, except that the ratio of Centella asiatica to 100 parts by weight of PHBH in the mixed solution was changed to 30 parts by weight. A photograph of the nanofibers is shown in FIG. The diameters of the nanofibers obtained are shown in Table 1.

(Example 4)
A sheet of nanofibers was produced in the same manner as in Example 1, except that the PHBH concentration of the PHBH solution obtained by mixing PHBH and HFIP as a solvent was changed to 2% by weight. A photograph of the nanofibers is shown in FIG. The diameters of the nanofibers obtained are shown in Table 1.

(Example 5)
A nanofiber sheet was produced in the same manner as in Example 2, except that the PHBH concentration in the PHBH solution obtained by mixing PHBH and HFIP as a solvent was changed to 2% by weight. A photograph of the nanofiber is shown in FIG. The diameters of the nanofibers obtained are shown in Table 1.

(Example 6)
A sheet of nanofibers was produced in the same manner as in Example 3, except that the PHBH concentration in the PHBH solution obtained by mixing PHBH and HFIP as a solvent was changed to 2% by weight. A photograph of the nanofibers is shown in FIG. The diameters of the nanofibers obtained are shown in Table 1.

(Example 7)
A nanofiber sheet was produced in the same manner as in Example 4, except that the humidity condition during electrospinning was changed to 20% RH. A photograph of the nanofibers is shown in FIG. The diameters of the nanofibers obtained are shown in Table 1.

(Example 8)
A nanofiber sheet was produced in the same manner as in Example 5, except that the humidity condition during electrospinning was changed to 20% RH. A photograph of the nanofibers is shown in FIG. The diameters of the nanofibers obtained are shown in Table 1.

(Example 9)
A nanofiber sheet was produced in the same manner as in Example 6, except that the humidity condition during electrospinning was changed to 20% RH. A photograph of the nanofibers is shown in FIG. The diameters of the nanofibers obtained are shown in Table 1.

(Reference example 1)
Electrospinning of a PHBH solution with a PHBH concentration of 1% by weight obtained by mixing PHBH and HFIP as a solvent without using Centella asiatica was performed under the conditions described in Example 1 to obtain nano-particles made of PHBH. A sheet of fiber was made. The diameters of the nanofibers obtained are shown in Table 1.

(Reference example 2)
Electrospinning of a PHBH solution with a PHBH concentration of 2% by weight obtained by mixing PHBH and HFIP as a solvent without using Centella asiatica was performed under the conditions described in Example 1 to obtain a nanoparticle made of PHBH. A sheet of fiber was made. The diameters of the nanofibers obtained are shown in Table 1.

In any of Examples 1 to 9, highly uniform nanofibers composed of a mixture of PHBH and Centella asiatica could be obtained. In Examples 1-3 and Examples 4-6, the resulting nanofiber diameter tended to decrease as the ratio of Centella asiatica to PHBH increased. In Examples 7-9, where the environmental humidity during electrospinning was relatively low, the nanofiber diameter was not significantly affected by the ratio of Centella asiatica to PHBH.

(Comparative example 1)
In the same manner as in Example 1, except that the Centella asiatica powder was directly mixed with the PHBH solution to prepare a mixed solution without preparing a Centella asiatica solution in which the Centella asiatica powder was dissolved in ethanol. Electrospinning was performed. The mixed solution contained an insoluble matter. As a result, it was impossible to stably produce nanofibers.

From each of the above Examples and Comparative Example 1, the Centella asiatica powder was dissolved in ethanol, the insoluble matter was filtered, mixed with the PHBH solution, and the resulting mixed solution was used to perform electrospinning. It can be seen that it is possible to electrospun in a controlled manner and produce nanofibers consisting of a mixture of PHBH and Centella asiatica.

(Example 10)
PHBH and HFIP as a solvent were mixed and stirred at 37° C. for 3 hours to obtain a PHBH solution with a PHBH concentration of 1% by weight.

The PHBH solution was mixed with emu oil and stirred at 37° C. for 1 hour to obtain a mixed solution containing 10 parts by weight of emu oil per 100 parts by weight of PHBH.

Then, using a nanofiber electrospinning unit manufactured by Kato Tech Co., Ltd., the mixed solution was electrospun to prepare a nanofiber sheet composed of a mixture of PHBH and emu oil. The electrospinning conditions were temperature 23° C., humidity 30% RH, injection angle 30°, flow rate 100 L/min, applied voltage 15-20 kV, and syringe pump speed 0.3 mm/min.

The diameter of the resulting nanofibers was measured and the evaluation is shown in Table 2.

(Example 11)
A nanofiber sheet was produced in the same manner as in Example 10, except that the ratio of emu oil to 100 parts by weight of PHBH in the mixed solution was changed to 30 parts by weight. The diameters of the resulting nanofibers are shown in Table 2.

(Example 12)
A nanofiber sheet was produced in the same manner as in Example 10, except that the PHBH concentration in the PHBH solution obtained by mixing PHBH and HFIP as a solvent was changed to 2% by weight. A photograph of the nanofibers is shown in FIG. The diameters of the resulting nanofibers are shown in Table 2.

(Example 13)
Same as Example 10 except that the PHBH concentration of the PHBH solution obtained by mixing PHBH and HFIP as a solvent was changed to 2% by weight, and the ratio of emu oil to 100 parts by weight of PHBH in the mixed solution was changed to 20 parts by weight. Then, a nanofiber sheet was produced. A photograph of the nanofibers is shown in FIG. The diameters of the resulting nanofibers are shown in Table 2.

(Example 14)
Same as Example 10 except that the PHBH concentration of the PHBH solution obtained by mixing PHBH and HFIP as a solvent was changed to 2% by weight, and the ratio of emu oil to 100 parts by weight of PHBH in the mixed solution was changed to 30 parts by weight. Then, a nanofiber sheet was produced. A photograph of the nanofibers is shown in FIG. The diameters of the resulting nanofibers are shown in Table 2.

(Example 15)
Same as Example 10 except that the PHBH concentration of the PHBH solution obtained by mixing PHBH and HFIP as a solvent was changed to 2% by weight, and the ratio of emu oil to 100 parts by weight of PHBH in the mixed solution was changed to 40 parts by weight. Then, a nanofiber sheet was produced. The diameters of the resulting nanofibers are shown in Table 2.

(Example 16)
Same as Example 10 except that the PHBH concentration of the PHBH solution obtained by mixing PHBH and HFIP as a solvent was changed to 2% by weight, and the ratio of emu oil to 100 parts by weight of PHBH in the mixed solution was changed to 50 parts by weight. Then, a nanofiber sheet was produced. The diameters of the resulting nanofibers are shown in Table 2.

(Example 17)
A nanofiber sheet was produced in the same manner as in Example 10, except that the PHBH concentration in the PHBH solution obtained by mixing PHBH and HFIP as a solvent was changed to 3% by weight. The diameters of the resulting nanofibers are shown in Table 2.

(Example 18)
Same as Example 10 except that the PHBH concentration of the PHBH solution obtained by mixing PHBH and HFIP as a solvent was changed to 3% by weight, and the ratio of emu oil to 100 parts by weight of PHBH in the mixed solution was changed to 20 parts by weight. Then, a nanofiber sheet was produced. The diameters of the resulting nanofibers are shown in Table 2.

(Example 19)
Same as Example 10 except that the PHBH concentration of the PHBH solution obtained by mixing PHBH and HFIP as a solvent was changed to 3% by weight, and the ratio of emu oil to 100 parts by weight of PHBH in the mixed solution was changed to 30 parts by weight. Then, a nanofiber sheet was produced. The diameters of the resulting nanofibers are shown in Table 2.

In any of Examples 10 to 19, highly uniform nanofibers composed of a mixture of PHBH and emu oil could be obtained. Moreover, from the comparison of each example, the higher the PHBH concentration of the PHBH solution, the better the miscibility of PHBH and emu oil, and the more uniform nanofibers could be obtained.

(Example 20)
Propolis and acetone as a polar solvent were mixed at a weight ratio of 1:10 and stirred to obtain a propolis solution.

Separately, PHBH and HFIP as a solvent were mixed and stirred at 37° C. for 3 hours to obtain a PHBH solution with a PHBH concentration of 2% by weight.

The propolis solution and the PHBH solution were mixed and stirred at 37° C. for 1 hour to obtain a mixed solution containing 100 parts by weight of PHBH and 30 parts by weight of propolis.

Then, using a nanofiber electrospinning unit manufactured by Kato Tech Co., Ltd., the mixed solution was electrospun to prepare a nanofiber sheet composed of a mixture of PHBH and propolis. The electrospinning conditions were a temperature of 23° C., a humidity of 20% RH, an injection angle of 30°, a flow rate of 100 L/min, an applied voltage of 15-20 kV, and a syringe pump speed of 0.2 mm/min.

A photograph of the nanofibers is shown in FIG. The diameter of the resulting nanofibers was measured as described above and the evaluation is shown in Table 3.

(Example 21)
A nanofiber sheet was produced in the same manner as in Example 20, except that the polar solvent for dissolving propolis was changed to ethanol. A photograph of the nanofibers is shown in FIG. The diameters of the nanofibers obtained are shown in Table 3.

(Example 22)
A nanofiber sheet was produced in the same manner as in Example 20, except that the ratio of propolis to 100 parts by weight of PHBH in the mixed solution was changed to 50 parts by weight. A photograph of the nanofibers is shown in FIG. The diameters of the nanofibers obtained are shown in Table 3.

(Example 23)
A nanofiber sheet was produced in the same manner as in Example 20, except that the polar solvent for dissolving propolis was changed to ethanol and the ratio of propolis to 100 parts by weight of PHBH in the mixed solution was changed to 50 parts by weight. A photograph of the nanofibers is shown in FIG. The diameters of the nanofibers obtained are shown in Table 3.

(Example 24)
A nanofiber sheet was produced in the same manner as in Example 20, except that the ratio of propolis to 100 parts by weight of PHBH in the mixed solution was changed to 70 parts by weight. A photograph of the nanofibers is shown in FIG. The diameters of the nanofibers obtained are shown in Table 3.

(Example 25)
A nanofiber sheet was produced in the same manner as in Example 20, except that the polar solvent for dissolving propolis was changed to ethanol and the ratio of propolis to 100 parts by weight of PHBH in the mixed solution was changed to 70 parts by weight. A photograph of the nanofibers is shown in FIG. The diameters of the nanofibers obtained are shown in Table 3.

In any of Examples 20 to 25, by dissolving propolis in a polar solvent such as acetone or ethanol, highly uniform nanofibers composed of a mixture of PHBH and propolis could be obtained. Moreover, from the comparison of each example, even when the propolis concentration was high, the miscibility of PHBH and propolis was good, and nanofibers with higher uniformity could be obtained.

In addition to being biodegradable and biocompatible, the nanofibers of the present invention can be used in medical material applications such as wound dressings with anti-inflammatory effects.

Claims (6)

a biodegradable polyester that is poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) ;
Nanofibers comprising a mixture of at least one anti-inflammatory agent selected from the group consisting of emu oil, centella asiatica, and propolis. The nanofiber according to claim 1 , wherein the content of the anti-inflammatory agent is 10 to 30 parts by weight with respect to 100 parts by weight of the biodegradable polyester. A method of making nanofibers comprising electrospinning a solution comprising a biodegradable polyester that is poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) and emu oil. A step of mixing a polar solvent solution of Centella asiatica and a solution of a biodegradable polyester that is poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) and electrospinning the resulting mixed solution. a method of making nanofibers, comprising: mixing a polar solvent solution of propolis and a solution of a biodegradable polyester that is poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) and electrospinning the resulting mixed solution. A method of manufacturing fibers. The method for producing nanofibers according to claim 4 or 5 , wherein the polar solvent is acetone or ethanol.

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