TW201016921A - Electrospinning compositions for the preparation of nanofibers and the applications thereof - Google Patents

Abstract

The present invention relates to a electrospinning composition for the preparation of nanofiber films, comprising (A) a uniform solution containing a cellulose acetate and a solvent, and (B) a tetracyclic compound and the derivates thereof; to a process for the improvement of conductivity and fineness of nanofibers based on cellulose acetates, comprising the step of applying the said composition through a electrospinning device to form nanofibers having improved properties of conductivity and uniform fineness; to a nanofiber film based on cellulose acetates exhibiting, simultaneously, excellent spinnability and good anti-bacteriall effect.

Description

201016921 ', invention description: [technical field to which the invention belongs] and a cellulose acetate nanofiber membrane material. The present invention relates to the improvement of the conductivity and fineness of the acetic acid sensitization. Method Decheng, [previous technical year] ❹ 15 20

It is known to use conventionally prepared cellulose acetate fibers (such as the method which is generally incapable of viewing __, (10) nai-vitamin H-nanofibers), and adding anti-two-two electrospinning to the nanofiber material. Silk technology * The effect of the child's nanofibers', especially for example, the nano-dimensional of the acid cellulose, to solve the above problem, the general balance plus Wei polymer, the example of the poly%, ethylene 'my Na miscellaneous wire The effect of Daqing Cheng Nai Weiwei. In addition, in order to control the effect of electrospinning, the nano-silver is usually added directly to the solution towel, but the knot is not good or the inspection ship is poor. Producing a merging material, which causes the spinning nozzle to clog and affects the electrospinning effect. A: t: -Ultrafme porous fibers electrospun from cellulose triacetate", Seong Ok Han et al, Materials Letters 59 (2005), PP 2998-3001, reveals The cellulose triacetate porous fiber was prepared by an electrospinning technique, and the effects of different ratios of co-solvents such as dichloromethane/alcohol (% to I:9) on the preparation of fibers and dimensions were compared. Triacetate cellulose fiber prepared by cosolvent The fiber form obtained is generally non-uniform and the fineness distribution is from micron to submicron. 4 201016921 Prior art: ''Electrospun cellulQse a_e — _aining chlorhexidine as a bactericide», Liang Chen et al, Polymer 49 (2008 ), ppl266· 'Jie Lin acetic acid _ her epoxy B _ polymer solution added antibacterial agent' such as chlorhexidine, and then static electricity _ to obtain antibacterial function of the 5 m fiber, however, the nanofiber obtained in this way The spinnability is not good, because the addition of chlorhexidine will affect the effect of electrospinning vinegar, it is necessary to add polyethylene oxide to improve this problem. 先前 Previous technology: "Gu microbial Cellulose acetate nan〇flbers silver nanoparticles», Won Keun Son et al, Carbohydrate Polymers 65 J〇(2〇〇6), PP430·434 'disclosed to the addition of bowl of silver acetate in the cellulose acetate polymer solution, f broken static _ turn After the nano-fiber ray, the uv lining finance provides the ability to set the nano silver to be reduced in the fiber. In this way, the rice-silver cellulose acetate nanofiber with antibacterial function can be obtained. However, the addition of nano silver directly to the polymer solution tends to cause aggregation, which affects the spinnability of the fiber. On the other hand, the addition of silver nitrate to the polymer solution 15 forms silver ions, which does not occur during electrospinning. Because the particles aggregate and ❹ affects the spinnability, the silver ions are reduced to nano silver by UV irradiation afterwards, but direct damage to the cells may occur due to the presence of unreduced silver ions. In the prior art, in order to avoid the influence of nano-silver aggregation on the spinnability of electrospinning, silver nitrate is generally used to form silver ions in a polymer solution, and 20 fibers are obtained by electrospinning to irradiate A nanosilver cellulose acetate nanofiber membrane having an antibacterial effect is obtained by UV light reduction of nano silver. Further, prior art:, Vitamin_Ioaded electrospun cellulose acetate nanofiber mats as transdermal and dermal therapeutic agents of vitamin A acid and vitamin EJ,, Pattama Taepaiboon et al, European Journal of 201016921

Pharmaceutics and Biopharmaceutics 67 (2007), pp 387-397, discloses the addition of vitamin A acid and vitamin E to a cellulose acetate solution, and the formation of a nanofiber film by electrospinning, which is useful for drug release applications. Basically, the addition of 5% by weight of retinoic acid/vitamin E to the polymer solution did not help to control the fineness of cellulose acetate 5. In order to improve the prior art problem of agglomeration due to the addition of additives such as nano silver or the like and to affect the spinnability of the fiber, the present invention provides an electrospinning composition containing a tetralin ginseng compound for use in Improve the conductivity of the cellulose acetate polymer solution 'and control the fiber diameter at the same time to obtain a more uniform diameter than the fine money. Rice fiber membrane. The invention further provides a method for reducing the particle size of nanofibers, which is an electrospinning effect of cellulose acetate. SUMMARY OF THE INVENTION In view of the present invention, it is an object of the present invention to provide a conductive silk composition which is characterized in that the conductivity of a solution of a four-Wee-Vitamin-Vitamin solution is used, wherein the composition comprises: "A a homogenous solution containing cellulose acetate and a solvent, wherein, in order to dissolve, the content of the cellulose acetate is 〇〇1, and the horse storm comprises trigaster r1 (four) and the solvent is selected from the group consisting of group one, one, one, Monomethyl hydrazine, dimethylformamide, ethanol, tetrahydrofuran, acetic acid and acetone or a combination of at least two of the above, B) 〇〇1 to 1 compound based on the weight of the above homogeneous solution Derivatives, 20 201016921

Οο

Ri is hydrazine or Ck alkyl, preferably η, R2 and R3 are each independently η, paa R ^ or Ci-6 alkyl, preferably H and CH3, each independently H or Ci6, preferably It is yang. In a specific example, the cellulose acetate in the electrospinning composition is selected from the group consisting of cellulose acetate, cellulose diacetate and cellulose triacetate, cellulose triacetate is preferred, and cellulose triacetate is used. optimal. Early DM _ 2_ to 35,000 g / Moule, preferably 25, _ to 3 〇, _ g / Mo Er. The ethyl acetate content of the cellulose acetate used is from 20 to 80% by weight, preferably from 3 to 7 % by weight based on the cellulose acetate. Preferably 40 to 55% by weight. And in the present invention, the content of the cellulose acetate is from 0.01 to 20% by weight based on the weight of the (iv) solution, preferably from 0.01 to 15% by weight, and more preferably from 0.01 to 8% by weight. According to the present invention, cellulose acetate is dissolved in a solvent to form a homogeneous solution, wherein the solvent may be a single solvent or a cosolvent mixture of two or more solvent combinations, and the solvent may be selected from the group consisting of trichloromethane, two Methyl chloride, dimethyl sulfoxide, dimethylformamide, 15 201016921

Ethanol, tetrahydrofuran, acetic acid and acetone 'preferably A dip #, 々 ,, 』, and live with this oxymethane and dimethyl hydrazine gluten or a mixed solvent of acetic acid and acetone. According to the present invention, the solvent is preferably a cosolvent comprising a di(iv) sulfone or a cosolvent comprising acetic acid and acetone, and the weight ratio thereof is i: 29 soil to 29.1' is preferably 1. to 2 〇: 丨, and best 丨: i to n 1. According to a preferred embodiment of the present invention, the solvent used is a listener comprising dichloromethane and hydrazide having a weight of i: 丨. Further, according to another preferred embodiment of the present invention, the solvent used is a total of 8:2 by weight of acetic acid and acetone, and in the present invention, the 'tetracycline compound, 'and, The derivative thereof includes an inorganic salt of a tetracyclic compound and a derivative thereof, such as a hydrochloride. According to the present invention, the tetracycline compound of the formula (1) and the derivative thereof in the electrospinning composition have the function of improving the conductivity of the cellulose acetate homogeneous solution, and in addition, the tetracycline compound can be further used as For antibacterial agents. According to a preferred embodiment of the present invention, the cyclin compound represented by the formula & 15 and derivatives thereof may be selected from the tetracycline 0 compounds and derivatives thereof represented by the following formulas (II) to (VIII), 'Dorsey Doxycycline

Tetracycline (II), 201016921

h3C\ ch3 Hq_CH3 , r '.OH

OH O OH Ο O Oxytetracy cline (III),

HO 0hh -:oh Minocycline

Chlortetracycline (Chlortetracy cline)

N2 H

(IV), (V), pemeclocycline (VI), 201016921

❹

Preferred are Doxycycline and Tetracycline, and doxycycline is preferred. (VIII) According to the present invention, the content of the tetracycline compound and its derivative of the formula 1 is from 8% to (8)% by weight based on the weight of the cellulose acetate homogeneous solution, and the weight is from 〇〇1 to 〇.20 by weight/ 〇' more preferably from 0.02 to 〇.12% by weight, and most preferably from 0.02 to 〇·ι〇 ίο during the fiber electrospinning process and can be directly fine and evenly distributed. In addition, ===, weaving only a good anti-effect of the fiber. According to the present invention: II. ', and prime 10 15 201016921 Antibacterial cellulose acetate nanofibers of less than 500 nm, preferably having a fiber fineness of 5 to 500 nm and 80 to 350 nm. For the best. In the present invention, the main component of the uniform solution of cellulose acetate in the electrospinning composition may alternatively be a composite material composed of cellulose acetate and another polymer, and a suitable 5 polymer embodiment is selected from the group consisting of: Polycaprolactone (poly(s-caprolactone), poly(ethylene oxide), polyvinyl alcohol (polyvinyl alcohol), polylactic acid (polylactic acid), polyurethane (polyurethane), polyglycolic acid (p〇lyglyc〇lic φ acid), P〇ly (β-hydroxybutyrate), cellulose (ceiiui〇se), Carboxymethyl Cellulose, chitin )/chitosan 10, collagen (c〇Uagen), gelatin, hyaluronic acid or Hyaluronan, aiginate, polyglutamic acid (y_p〇ly (glutamic add) The electrospinning composition of the present invention can selectively add additives such as surface graft/immobilized substances or fiber additives, such as antibodies, enzymes, proteins, functional group-containing polymers, bacteria, cells, surfactants. , nano metal particles, micro-glue 15 /Nano rubber®, drugs, activated carbon, carbon nanotubes, salts, polyelectrolytes, catalysts, etc. _ Substance. Another object of the present invention is to provide an improvement in the conductivity and fineness of cellulose acetate nanofibers. The method comprises the steps of: A) adding 1 to 20% by weight of 〇., preferably 〇〇1 to 15% by weight and more preferably 〇〇ι 2 to 8% by weight of cellulose acetate polymer Adding a human-to-face towel, a solution containing a cellulose acetate polymer, wherein the co-solvent is composed of two solvents selected from the group consisting of dichlorohydrazine, dimethyl sulfoxide, acetic acid and acetone. The weight ratio is: 29 to 29: 1; B) 0.01 to 1.00% by weight, preferably 〇〇1 to 〇2〇% by weight, more preferably 〇〇2 201016921 to 0.12 by weight from the best. 〇2 to the weight% of the tetracycline compound is added to the prepared polymer solution to obtain an acetic acid-based polymer solution having a conductivity between the illusions, the tetracycline compound and its derivatives: ;

Ο

Ri is Η or (: μ6 alkyl, R2 and R3 are each independently H, 〇H or C _6 alkyl, R4 and & are each independently η or Cm alkyl, Q will be prepared in step B) The polymer solution passes through a nanofiber comprising a spinning nozzle and an electrode device whose operating voltage is between about 8 and 35 nm, and between 50 nm and 500 nm. According to one embodiment of the method of the present invention, cellulose acetate cellulose, cellulose diacetate and cellulose triacetate, cellulose acetate acetate is preferred, and cellulose triacetate is used. optimal. ▲Cellulose and three

The cellulose acetate used in the process of the invention has a relative molecular weight of 35,000 g/mole, preferably 25, 〇〇〇 to 3 〇, and 〇〇〇克/莫干围为20,00C. The acid used in the process of the invention The B-transfer in the cellulose contains 80% by weight/0, preferably 3% to 7% by weight, most preferably 2% to preferably 40% to 55% by weight, based on the weight of 12 201016921 cellulose acetate. . According to the method of the present invention, the co-solvent mixture of the two kinds of dissolved complexes may be used, 5

20

Preferably, a mixed solvent of dichloromethyl dimethyl ketone or a mixed solvent of acetic acid and propylene is used. The method of the present invention has a weight ratio of preferably from 1:10 to 20:1, more preferably from 1:1 to 18:^= of 1.1. Further, the solvent used in the method of the present invention is a co-solvent of acetic acid and _, and the weight ratio is preferably 1:1 () to 2 (): more preferably: i to 18: and the best ^ 8 = 2. In the present invention, a cellulose acetate polymer homogeneous solution is charged by a high voltage (for example, 5 to 8 〇 kV) by an electrospinning method, and the rice fiber is dried and solidified. According to the specific example of the present invention, in the method of providing high=pressure, the syringe equipped with the metering pump sprays the polymer solution, and each time the field strength is gradually increased, Raw half _ fluid table: extended to form a conical shape (such as the so-called Taylor conical (Tayl〇rc〇ne)); continue to increase the electric field strength '- once turned a certain threshold, its static repulsion exceeds the Herhe surface tension value 琢 conical The charged fluid at the head end produces a Confucian phenomenon, in which the solvent evaporates to form nanofibers on the collection crucible. In the electrospinning device, the electrode is spun, the valley liquid or the county body, and the electric collector is connected to the reclining or stationary collector. According to the method of the present invention, the vinegar g-vitamin is selected from the group consisting of cellulose monoacetate, dicellulose or cellulose triacetate, and the cellulose acylate and tri-cellulose are: «The present invention is a fine succinyl cellulose material.四 According to the present financing method, the tetracycline compound and the system of the method towel are selected from the group consisting of doxycycline, tetracycline, oxytetracycline, minocycline, and chlorotetracycline 20 201016921 ❹ ίο. 15 ❿ 20 Yuxisu, dimecycline or tigecycline is best with doxycycline. * It is better to use oxime and tetracycline, and the external 'except _ improve and control the nanofiber _ outside the outer diameter' can reduce the fineness of the nanofiber and make the particle size distribution more uniform. The (four) Chi Yuqi material is produced, and the improved impurity is obtained according to the method of the present invention. According to the present invention, it is preferred that the obtained weiweiwei is ir with G to nano, and (10) to the present Naito worm U-face 'this (four)_electrospinning technique, the cellulose acetate fiber is prepared to be equal to the addition thereof. Tetracycline compounds (such as multiplexin, tetracycline) provide the antibacterial function of cellulose acetate nanofibers. Rice fiber: a further object of the present invention - the purpose of producing a kind of antibacterial function, the cellulose acetate nanofiber membrane obtained according to the invention can be further processed into a household: the desired product form 'used processing The method includes, for example, interfacial polymerization, coating, entanglement, heating, plasma modification, grafting, immobilization, crosslinking, hydrophilization/hydrophobization, lamination, or in its wire (when weaving, metal (four), etc. ) Spinning and the like. The cellulose acetate nanofiber membrane obtained by the present invention can be further modified to form a fiber type, such as a solid (four), a multi-recorded type, a pure type, and a towel (four) fiber. The nanofiber material obtained by the present invention can be combined with or with its wire f (e.g., non-woven, polymerization, fine bonding, etc.), which can be further processed, for example, 14 201016921 201016921 5

15

20, enzyme immobilization, resin coating, hot pressing and other treatments ^= Nai __ (four) Lin each paste way, especially the medical 丄T purification (Η _ Ρ 6 pool ―) / blood through _em〇dia (four): make Cai Ming electrospinning Silk nanofiber membranes are used for blood purification. The membrane is used as a semi-dialysis membrane =:== The rice fiber membrane can be used for blood permeation or antibodies (4), and the effect of biosensing can be achieved by the combination of enzyme or antibody binding and _ quality. Ship 3f / turn = (DrugDelivery): the nanofiber made of the electrospinning composition of the present invention, the quasi-medium agent (such as drug microcapsules, drug particles, etc.), can be directly released 2 or controlled release (utilization) "Wound dressing" by means of temperature, acid value, hydrophilic and lipophilic properties, etc. · The fiber membrane made of the electrospinning composition of the present invention is suitable for covering as a covering, except It can be applied directly to single-component fibers or in the form of composite fibers. 5. Tissue engineering scaff〇ld: The m-turned into the tissue ball holder made of the electrospinning composition of the present invention can be applied directly or in the form of a composite fiber. [Embodiment] 15 201016921 The present invention will be more detailed by the following description, and the embodiment is not intended to limit the scope of the invention in any way, although the numerical range and parameter range set in a wide range are approximate, but are recorded as accurately as possible. The values in a particular embodiment. 5 EXAMPLES The electrospinning apparatus and operating conditions used in the examples and comparative examples of the present invention are as follows: Ο L electrospinning apparatus (model ESL-004, manufactured by Shuttle Ring Co., Ltd.) contains a polymer for melting gold Feed head_input device, needle 10 tube '-metal needle' for weaving polymer solution--a power supply and a substrate for collecting fibers. 2. Operating conditions: The voltage of electrospinning operation is 2〇kv The propulsion pressure is αι bribe, the metal needle size is 25 gage, and the distance between the tip of the metal needle and the substrate is 1 〇 cm. 15 The cellulose acetate nanofiber obtained by the examples and the comparative examples of the present invention is electrostatically spun, '糸 composition The properties of the material and its coffin were evaluated and determined according to the following methods: h Nanofiber structure/nano fiber particle size distribution using a scanning electron microscope (SEM) device (Model J0EL JSM_67〇〇F, manufactured by J〇EL) ) 5, 〇〇〇 magnification, observe the structure of nanofibers and fine 20 cloth. 16 1. The conductivity of polymer solution is measured by electric resistance meter (model SC-SRT Surface Resistant, manufactured by Hongxing Electric Co., Ltd.) molecule Conductivity of liquid (1/Ω) 201016921 3. Anti-effect A) Qualitative bacteriostatic test: Qualitative test of antibacterial properties of nanofiber membrane 5 using standard AATCC (American Association of Textile Chemists and Colorists) Test Method 147 Sex, the operation process is as follows: - Prepare the fine halogen medium: uniformly mix 23.5 grams of agar extract (Nutrient Agar) / 1 liter of water and 8 grams of nutrient medium (Nutrient Broth) / l liter of steam, then form The medium of cockroach is sterilized in a high temperature autoclave to prepare a bacterial culture medium; - broth culture. Staphylococcus aureus (Glendido 10) is added to the sterilized medium to culture 18 24 hours; - Test sample: Prepare a sample of sterilized electrospun cellulose acetate nanofiber membrane with a size of 2 cm x 2 cm; - Test procedure: Place the sterilized medium in an aseptic table and pour before coagulation Into the culture dish 'to make a plate medium; inoculate the strain in the plate medium and uniformly coat with a L 15 type glass rod, and use the nanofiber film and the film formed by coating to utilize φ Sterile pliers were carefully placed on the surface of the vegetable gum and adhered to the plate medium, and cultured in a 3Tc temperature incubator for 24 hours. -Effect of the evaluation: The antibacterial effect of the nanofibers was evaluated by the size of the membrane inhibition zone. The larger the inhibition zone, the better the bacteriostatic effect. 20 B) The anti-halogen test of 疋. Use jjs indust]: iai l 1902 standard method to test, the operation process is as follows: VII, test organisms Staphylococcus aureus Prepare the bacterial culture medium. Put 5 grams of beef extract, 10 grams of protein gland 201016921 (peptone), 5 grams of sodium chloride, 15 grams of acacia and 1000 ml of pure water into the flask. Medium and medium homogeneous mixing; heating in a boiling water bath to fully dissolve the components of the mixture, and then adjusting the pH of the mixture to pH 7.0 ± 0.2; then, sterilizing in a high temperature autoclave to form a bacterial culture medium; - test sample : Preparing a sample of sterilized electrospun cellulose acetate nanofiber membrane having a size of 4 mm × 4 mm; - Test procedure:

15

Day 1 : bacterial activation, the strain was introduced into the culture solution and cultured in a 3Tc incubator for 18 to 24 hours;

Day 2: Calculate the initial bacterial count, dilute to a concentration of 1χ1〇5 per ml, and then evenly drip the liquid onto the membrane until the membrane is filled with the bacterial solution; then place the membrane filled with the bacterial solution Incubate in its incubator for 18 to 24 hours;

Day 3: The Day 2 film is placed in a 2 〇 ml ship for more than i minutes. After that, the obtained liquid is diluted to the original concentration of 1〇_5, and the diluted liquid is applied to the acacia plate. Cloth, cultivated in a trough for 18 to 24 hours; °

Day4: Calculate the result of Day3; f. Miscellaneous: the scale is calculated as the case. When the nanometer age is greater than 0, the mosquito sample has a bactericidal effect. When the temperature is 2, the sample is evaluated to have a g-suppressing effect. A field antibacterial value is greater than the conductivity test ::r electrospinning composition preparation and 20 201016921 dressing * 3 there is called Wei compound static riding, monoacetic acid _ solution as a pair of knowledge. Weigh 15 grams of monoacetate raw material (relative to the molecular flavonoids in the glass, add the (10) grams of acetic acid and &= acetic acid / _ (8.2) listener, in a shock to make the reference 10 15 20: = homogeneous solution. Conductivity of the solution obtained above was carried out. Example 1 I5 g of monofilament _ _ Gu Gu (relative molecular weight 29, _ inspection company) was placed in a glass bottle, and == acetic acid / _ was added thereto (8: 2) a uniform solution of silk mash and 17 g of acetone cellulose acetate. 均匀 Make uniform 'to obtain 2 gram of doxycycline plus a single acetic acid obtained above, and mix well to obtain _% doxycycline monoacetate fiber = liquid filament uniform solution, test the conductivity of the solution, the results are shown in the table. ', the electrospinning example 2 as in the case of Bay example 1 The cellulose monoacetate had a stable doxycycline content of 4 g to obtain a uniform solution of electrospinning containing _% of the doxycycline solution. The uniform sound of the early acetate fiber was then tested. 1

Comparative Example B 19 201016921 A cellulose triacetate electrospinning solution containing no tetracycline compound was prepared as a control group. ..., weighed 8 grams of three free acid cellulose raw materials (ethyl mercapto content of 43 to 49% by weight, the commodity AL-181005 'purchased from Sigma_Aldrich) placed in a glass bottle, in which added magical 5 dichlorodecane, let After the solution was kept at 40 ° C for one day, add 42 g of dimethyl sulfoxide to mix the solution evenly in a shock disk to obtain dichlorohydrazine/dimercapto sulfoxide (1:1). A homogeneous solution of cellulose triacetate in a cosolvent. The conductivity measurement of the above obtained liquid was carried out, and the results are shown in Table 1. Ίο Example 3 8 g of triacetate fiber was weighed, and the raw material (ethylene bromide content 43 to 49 wt%, commercial 1181005 'purchased from Sigma-Aldrich) was placed in a glass bottle, and 42 g of chlorodecane was added thereto. After allowing the solution to stand at 403⁄4 for one day, add 42 g of dimethyl sub-milling to uniformly mix the solution in an oscillating manner to obtain a solution of cellulose triacetate. h Weighing 84 g of doxycycline into the uniform solution of cellulose triacetate obtained above, and after mixing uniformly, obtain a uniform solution of cellulose triacetate electrospinning containing 2% doxycycline, and test the solution. The conductivity is shown in the table. 2) Example 4 As in the method of Example 3, except that the content of doxycycline in the trimethylcellulose electrospinning homogeneous solution was 3.68 g' to obtain 〇.〇4〇/0 doxycycline A cellulose triacetate electrospinning homogeneous solution. Next, the conductivity of each solution was tested, and the results are shown in Table i. 0 20 201016921 Example 5 As in the case of Example 3, except that the content of the cellulose in the triacetate electrospinning homogeneous solution was 736 g. % doxycycline triacetate fibrin electrostatic _ record. (4) 戦 溶 四 (4) Wei degree, hiding as shown in Table 施 Example 6 丨. The eve was the same as that of Example 3 except that in the cellulose triacetate electrospinning homogeneous solution, the male content was 9.2 g' to obtain the triacetate fiber containing G1G% doxycycline. Electrospinning uniform solution. Next, the conductivity of each solution was tested, and the results are shown in Table i.

As shown in Table 1, 'the conductivity of the electrospinning composition obtained in Examples 1 to 6 was lower than that of the composition containing no doxycycline (Comparative Example A and Comparative Example %). 21 201016921 n. Electrospun nanofiber injury and fiber comparison example c The electrospinning procedure obtained in Comparative Example A was not included. In the case of monoacetic acid cellulose (4) in which the cellulose acetate was uniformly solutiond, ,: Saki (4) loading The uniform solution obtained by Comparative Example A is sprayed. In the electrostatic material, the device squeezes the solution into a metal needle, solidifies it, and distributes the solvent in the solution on the collector (10) e 10 15 ❹ Figure I The above picture m is transferred to the fineness and distribution of _, the results are as shown in Table 2 and Example 7 η - ^ 1 case 1 containing a uniform solution of monoacetate containing 〇. 〇 2% cycline into the lamp electrospinning Wire program: a single-cellulose uniform solution obtained by filling the syringe of the electrospinning device, and the _ propelling device extrudes the solution into the metal head to eject the solution from the solution. In the static _ process towel, the solution is made The solvent is evaporated and then HHb' is formed on the collected H to form nanofibers respectively. The results of the fineness and distribution of the nanofibers are shown in Fig. 2a and Fig. 2b. Example 8 As in the electrospinning procedure of Example 7, the bismuth 4% doxycycline obtained in Example 2 was obtained. The monoacetate uniform solution was subjected to an electrospinning process to form nanofibers. D. The fineness and distribution of the nanofibers formed were measured. The results are shown in Tables 2 and 22, 201016921, Figs. 3a and 3b.

Comparative Example D In the electrospinning procedure of Comparative Example C, a uniform solution of cellulose triacetate not containing doxycycline obtained in Comparative Example b was subjected to an electrospinning procedure to form a nanofiber. For the above-mentioned shape, the fineness and distribution of the axis are shown in Table 2 and Lutu 4a and 4b. 10 15 ❹ 20 Example 9 As in the electrospinning procedure of Example 7, the uniform solution of cellulose triacetate containing the read % obtained in Example 3 was subjected to electrostatic_rotation, (10) into nanometers to the above-mentioned shape (four) m-axis row. The detection of fineness and distribution is shown in Figures 5a and 5b. . Example 10 As in the electrospinning procedure of Example 7, the three-concentration containing 〇〇4%=cycline obtained in Example 4 was uniformly dissolved and electrolyzed, (10) into nanometers to form the above-mentioned nanometer. The fibers were examined for fineness and distribution, and the results are shown in Table 2 and Figures 6a and 6b. Example 11 23 201016921 As in the electrospinning procedure of Example 7, the poly-nuclear-containing tri-nuclear material obtained from Example 10 was self-dissolving the electric lining procedure to form nanofibers. The fineness and distribution miscellaneous measurements were carried out on the above formed nevi, and the results are shown in Table 2 and Figure 7. Example 12 Referring to the electrospinning procedure of Example 7, the uniform solution of cellulose diacetate containing 〇·1〇〇/0 doxycycline obtained in Example 进行 was subjected to an electrospinning procedure to form nano 10 fiber. The fine-distribution miscellaneous measurement of the nevavir formed above was carried out, and the results are shown in Table 2 and Figure 8. Table 2 tbfe Example C Hybrid 7 Subtle 8 tbfe Example D 9 Hybrid 10 Fine to 11 Hybrid 12 Monoacetate, % 0 15 15 Two gammonic acid cellulose, % 0 8 8 8 8 Dorsalin ,% 0 0.02 0.04 0 0.02 0.M 0.08 0.10 Average fiber diameter (4) 521.47 ±40138 441*50 珊.58 35936 ±61.84 "1186.03 ±81229 49029 ±123.13 150.92 ±6634 105.48 ±33.73 96.70 i3237 The content of doxycycline is increased, and the effect of reducing the particle size of the nanofibers and uniformly distributing the fineness is better. As shown in Table 2, the cellulose acetate electrospinning composition containing no doxycycline (Comparative Example) C and Comparative Example D) In contrast, the cellulose acetate electrospinning composition of the present invention (Examples 7 to 12) was subjected to electrospinning 24 201016921 ^ 〇 ^ la. 2a. ^ = = 6 = θ7 and 8 The measured fiber particle size distribution shows that when the nanofiber ==1 is increased, the particle size becomes smaller and tends to be uniform. In the above examples, the material is opened / _^: ° 2 to 1 ()% The cellulose triacetate electrospinning consists of a silk that is not formed. It is shown in 6a, 7 and 8 on the thin button. 4 ^ ui 筹 10 ❹ 20 III. Antibacterial test of nanofiber membrane A) Qualitative bacteriostatic test = the above qualitative bacteriostatic test method, taking the ruthenium of triacetate without doxycycline ( Comparison and evaluation of the bacteriostatic ability of the nanofiber membrane formed by electrospinning of the cellulose solution containing _ ί 口 哀 纤维素 纤维素 纤维素 纤维素 实施 。 。 。 。 。 。 。 。 。 。 。 。 。 。 9 9 The performance is not 'the addition of doxycycline triacetate pair == membrane does not inhibit _ formation on the medium, that is, does not have antibacterial effect; there is i to release ίί Γ. ° Γ ° doxycycline triacetate Cellulose nanofiber membranes can be suppressed by the sample week, as shown in Figure 5%, so they are found to have the ability to touch. B) Quantitative antibacterial test is applied to the antibacterial test method, the sample contains 0% (Comparative Example D), 〇.〇2% (actually transferred to each of her Examples 1〇) and 〇.〇8% (Example U) of the doxycycline triterpenic acid was formed by electrospinning of a flat liquid The value of the bacteria and the antibacterial value of the nanofiber riding were not evaluated, and the antibacterial ability of the rice fiber was as shown in Table 3. 25 201016921

The multi-display of ❿, the cellulose acetate electrospinning containing 嶋 to 喔 organism: knows that tetracycline compound or its derivative is added. Furthermore, since the tetracycline compound or the material itself has a batch phase energy, the nanofiber film formed by the above-mentioned bright film can have excellent antibacterial property at the same time. According to the technique of the present invention, the upper frequency is implemented. _, so that the general knowledge of the field of n can understand the content of the second case of this case, and use the limit (4), so the improvement or repair of the invention (10) and the spirit of the present invention should still be covered by the present invention. Fan is inside. BRIEF DESCRIPTION OF THE DRAWINGS Fig. la is a monoacetate (CA) nanofiber membrane containing 10% doxycycline (10). 26 15 201016921 Example C) Particle size distribution diagram lb c) Leg ίί Cyclocycline single with _ her_film shouting example e 10 15 ❹ Example η map = cloth with 〇. 〇 2% doxycycline single-acid acid cellulose nanofiber canister example == 瞧乡神细The __mei shaft (implementing Fig. 3a is a single vinegar example 8 containing 0.04% doxycycline). The SEM image of the early rice-transfer film (implementation Fig. 3b is a monoacetate cellulose containing 0.04% of cilostatin). β Figure 4a shows the particle size distribution of a cellulose triacetate (TAC) nanofiber membrane containing 〇〇/〇 doxycycline (Comparative Example D). Figure 4b is an SEM image of a cellulose triacetate nanofiber membrane containing 〇% doxycycline (Comparative Example D). Fig. 5a is a particle size distribution of a cellulose triacetate nanofiber membrane containing 0.02% doxycycline (Example 9). Figure 5b is an SEM image of a cellulose triacetate nanofiber membrane containing 0.02% doxycycline (Example 9). Figure 6a is a particle size distribution of Example 10) containing 0.04% doxycycline. An SEM image of a cellulose triacetate nanofiber membrane (Fig. 6b is a sample containing 0.04% doxycycline Example 10). Fig. 7 is a particle size distribution of a cellulose acetate nanofiber membrane containing 0.08% of doxycycline (implementing a cellulose acetate nanofiber membrane (Example 20 201016921 11). Fig. 8 is a mixture containing 0.10% of doxycycline. The particle size distribution of the cellulose triacetate nanofiber membrane (Example 12). Figure 9a is a qualitative bacteriostatic test of a cellulose triacetate nanofiber membrane containing 0% doxycycline (Comparative Example 5 D). Results Fig. 9b shows the results of qualitative bacteriostatic test of cellulose triacetate nanofiber membrane containing 0.02% doxycycline (Example 9). Θ [Explanation of main components] 1〇28

Claims (1)

201016921 VII. Patent application scope: 1. An electrospinning composition for manufacturing a nanofiber membrane, comprising: A) a homogeneous solution containing cellulose acetate and a solvent, wherein, based on the weight of the solution, The content of cellulose acetate is 〇.〇1 to 20% by weight, and the solvent is selected from the group consisting of three 5 gas smoldering, one gas smoldering, diterpene sulphur, dimethyl sulphamine, ethanol, and four. Hydrogen oxime n, acetic acid and propylene _ or a combination of at least two of the above, Β) based on the weight of the above homogeneous solution, 〇〇1 to 1% by weight of the tetracycline φ compound of formula 1 and its derivatives, 29 201016921 The content ranges from 20 to 80% by weight based on the weight of cellulose acetate. 6. The composition according to item 5 of the patent application' wherein the acetic acid content in the cellulose ranges from 30 to 70% by weight based on the weight of the cellulose acetate. 7. The composition according to item 6 of the patent application, wherein the content of the ethyl acetate in the cellulose acetate is 40 to 55% by weight based on the weight of the cellulose acetate. 8. The composition according to claim 1, wherein the cellulose acetate is present in an amount of from 0.01 to 15% by weight based on the weight of the homogeneous solution. /. . The composition of the eighth aspect of the patent application, wherein the cellulose acetate is present in an amount of from 0.01 to 8 by weight based on the basis of the uniform solution. /. . 10 10. The composition according to the first aspect of the patent application' wherein, in the tetracycline compound of the formula (I), R~i is Η, R_2 and & are each independently Η and CH3, and R4 and R5 are cpj3. 11. According to the composition of the patent clearing of the first paragraph of the patent, 'the tetracycline compound and the potted derivatives are Doxycycline, Tetracycline, Oxytetracycline, and Menocycline. (Minocycline), Chlortetracycline, Demecl〇cycline or Tigecycline. 12. The composition according to item η of the patent application, wherein the tetracycline compound of formula 1 is doxycycline. 13. The composition according to the first aspect of the invention, wherein the content of the tetracycline compound of the formula (I) and the derivative thereof is from 0.01 to 0.20% by weight based on the weight of the cellulose acetate homogeneous solution. 14. The composition according to claim 13 wherein the content of the tetracycline compound and the derivative thereof of the formula (I) is from 0.02 to 0.12% by weight based on the weight of the cellulose acetate homogeneous solution. 30. The composition of claim 14, wherein the content of the tetracycline compound of the formula (1) and the derivative thereof is from _ to 0.10% by weight based on the weight of the cellulose acetate homologous solution. 16· According to the scope of the patent application! The composition of any one of the items 15, wherein the tetracycline 5 compound and the derivative thereof further have an antibacterial function. Π. According to the composition of the scope of the patent, the solvent is a co-solvent of methylene chloride and dimethyl sulfoxide or a co-solvent of acetic acid and propylamine. ❹ 18. According to the scope of the patent application a composition wherein the solvent component in the cosolvent has a weight ratio of 1:29 to 29:1. 1〇19. The composition according to claim 18, wherein the solvent component in the cosolvent has a weight ratio of 1 : 10 to 20 : ! 20. The composition according to claim 19, wherein the solvent component in the cosolvent has a weight ratio of 1:1 to 18: 1. 21. According to the scope of claim 2 The composition, wherein the cosolvent is a cosolvent having a weight ratio of dichloro"methyl dimethyl hydrazine to dimethyl hydrazine of 1: i or a cosolvent having a ratio of acetic acid to propylene glycol of 8:2. 22. The composition according to item i of the patent application has a conductivity of between 1 〇 3 and 10 _ 7 1 / Ω. 23. A method for improving the conductivity and fineness of cellulose acetate nanofibers, wherein the package 20 comprises: A) adding 0.01 to 2% by weight of 1% cellulose acetate polymer to a cosolvent to prepare - The invention comprises a cellulose acetate polymer solution, wherein the towel is composed of two solvents selected from the group consisting of dichloropyrene, dimercaptopurine, acetic acid and acetone, and the weight ratio thereof is from 1 to 29 to 29 : 1 ; 201016921 B) 0.01 to uo weight% tetracycline compound addition liquid to obtain a conductivity of (5) to 1 (r7 = with I such as molecularly soluble molecular solution, wherein tetracycline compound is _ four riding fiber Su Gaoqi 〇ΟΗ 〇 _, J Wang Chu. Νη2 Rj R2 R3 ❹ (I) wherein &amp; is 11 or (:1_6 alkyl, R2 and R3 are each independently H, 0H or C16 alkyl, and ^4 and Rs are each independently Η or Cm alkyl , Lu C) will dissolve the polymer of ^Cong to the electrostatic containing the nozzle and the electrode. The operating voltage range is from 5kV to NZV, and the spinning has a straightness of 50nm to 500nm. Intercrystalline fiber. According to the method of claim 5, wherein the cellulose acetate is selected from the group consisting of monocellulose or cellulose triacetate. </ RTI> 25. The method according to claim 23, wherein the cosolvent is a cosolvent containing methylene chloride and monodecyl hydrazine or a cosolvent containing acetic acid and acetone. 26. The method according to claim 23, wherein the tetracycline compound and its derivative are doxycycline, tetracycline, oxytetracycline, minocycline, chlorotetracycline, dimecycline or tigecycline Prime. 27. The method according to claim 26, wherein the tetracycline compound is doxycycline. s. The method is made. Like the patent of the Jiaming squad 23 30. A kind of antibacterial acetate fiber singular direct brake n i fiber riding, which is characterized by the application of patent Fancai 1 to 22 towel--plants. </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; ❹ 33