CN102389395A - Preparation of n-HA/PLGA electrostatic spinning composite nanofiber medicament loading system - Google Patents

Abstract

The invention relates to a preparation method of an n-HA/PLGA electrospinning composite nanofiber drug-loading system, comprising: (1) dissolving a water-soluble drug in deionized water to obtain an aqueous solution of the drug; dispersing n-HA in deionized In water, ultrasonically disperse evenly to obtain n-HA suspension; (2) under stirring, add the aqueous solution of the above drug dropwise to the above n-HA suspension; centrifuge to obtain a precipitate, wash the precipitate with deionized water, freeze Dry and filter to obtain drug-loaded n-HA; (3) ultrasonically disperse the above-mentioned drug-loaded n-HA in a THF/DMF mixed solvent, add polylactic acid-glycolic acid PLGA to make a spinning solution, and then perform electrospinning Silk, that is. The preparation method of the invention is simple and easy to operate, and the used polymer has good biocompatibility; the n-HA/PLGA dual-carrier drug-loading system of the invention has good drug sustained release effect.

Description

Preparation of n-HA/PLGA Electrospinning Composite Nanofiber Drug-loading System

technical field

The invention belongs to the field of preparation of a drug-controlled release system of n-HA/high polymer composite nanofiber felt, and particularly designs a preparation method of n-HA/PLGA electrospinning composite nanofiber drug-loading system.

Background technique

In recent years, with the vigorous rise of nanotechnology and the continuous emergence of various biocompatible polymer materials, nanoscale drug delivery systems based on polymer materials have attracted widespread attention. In order to change the burst release phenomenon of traditional medicines, improve the utilization rate of medicines and reduce the toxic and side effects on human body, the development of drug controlled release system with sustained release effect has always been a research hotspot.

Electrospinning technology is a method in which a charged polymer solution (or melt) flows and deforms in an electrostatic field, and is solidified by volatilization of the solvent or cooling of the melt to obtain a fibrous substance. In 1934, Formhals published his first patent for an invention involving a method and apparatus for producing man-made fibers by electrospinning. In 1969, Taylor studied the shape of polymer droplets formed at the spinneret when an electric field was applied, and discovered the well-known "Taylor cone", and the subsequent research on electrospinning was relatively slow. Until the mid-to-late 1990s, with the rise of nanotechnology, people realized the potential application value of nanofibers in many fields. The research team led by Doshi and Reneker conducted breakthrough research on electrospun nanofibers. Electrospinning technology It has received people's attention again and gained rapid development.

The biodegradable and biocompatible polymer nanofibrous scaffold by electrospinning has the characteristics of controllable fiber size, large specific surface area, high porosity and three-dimensional network structure, which can be very good in terms of biological function and structure. Therefore, nanofibers have been widely used in tissue engineering, and the electrospun nanofiber drug delivery system has attracted more attention in the past ten years. In 2001, Ignatious and Baldoni were the first to use electrospun nanofibers to design composite agents with different drug release characteristics such as fast, instant, delayed, slow, continuous and staged. Subsequently, the researchers soaked the electrospun nanofiber mat with the drug solution; mixed the drug molecule and the polymer solution for electrospinning; prepared the W/O or O/W emulsion of the drug molecule and the polymer solution for electrospinning, That is, emulsion electrospinning; or preparation of coaxial electrospun nanofibers in which the core layer is a drug solution or a mixed solution of a drug and a polymer, and the shell layer is a polymer solution. These electrospun nanofiber drug-loading systems can improve the drug burst release phenomenon to varying degrees, however, electrospun nanofiber scaffolds have the problem of low mechanical strength. Therefore, it is an inevitable development trend to research and develop nanofiber drug-loading systems with high mechanical properties and good sustained and controlled release effects.

Nano hydroxyapatite (Nano hydroxyapatite, n-HA) is a calcium phosphate salt with a molecular formula of Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ . The synthesis methods of n-HA can be divided into two categories in essence: one is the synthesis method from top to bottom, that is, the bulk material is refined to obtain nanoparticles by mechanical means (such as the ball rubbing method); the other is the synthesis method from bottom to bottom. Synthesis methods on the surface, that is, direct synthesis of nanoparticles from the molecular or atomic level, such as wet chemical method, co-precipitation method, microemulsion method, etc. n-HA is mostly needle-shaped, rod-shaped, and porous, with a large specific surface area and strong surface adsorption capacity, and can adsorb and deliver a variety of drugs. Its research as a drug carrier has received extensive attention. Tomoda et al. found that the adsorption and release characteristics of n-HA to proteins are related to the shape of n-HA. Spherical n-HA particles have strong surface adsorption capacity, and have a sustained release effect on small molecule drugs, reducing the effect on Toxic side effects of the body.

When n-HA is used as a drug carrier alone, there will be problems such as drug burst release. Boonsongrit et al. realized the loading of bovine serum albumin (BSA) by n-HA through an ex-situ loading method, and found that in PBS buffer, there was a burst release phenomenon in the spherical n-HA-BSA system, and the release of BSA within 30 minutes The amount can reach 70%. Therefore, they prepared PLGA/n-HA composite microspheres by solid/oil/water (S/O/W) emulsion solvent evaporation method, and successfully realized the sustained release of n-HA-BSA system under physiological conditions. This shows that by compounding with a specific polymer to form an inorganic/organic hybrid drug carrier, the drug burst phenomenon that occurs when n-HA is used alone as a drug carrier can be improved to a certain extent. At the same time, n-HA is an inorganic nanomaterial with good mechanical properties and good thermal stability, and its nanoscale diameter also makes it suitable as a reinforcement for composite materials.

Retrieval of literature and patents on electrospun nanofibers at home and abroad shows that: it has not been found to use n-HA and polymer composite electrospinning to enhance the mechanical properties of electrospun nanofiber mats, and to prepare n-HA/PLGA It is a dual-carrier drug-loading system.

Contents of the invention

The technical problem to be solved by the present invention is to provide a preparation method of n-HA/PLGA electrospinning composite nanofiber drug-loading system, the method is simple, easy to operate, the polymer used has good biocompatibility, and the obtained The n-HA/PLGA dual-carrier drug-loading system has a good sustained-release effect of drugs.

A preparation method of an n-HA/PLGA electrospinning composite nanofiber drug-loading system of the present invention, comprising:

(1) Dissolve the water-soluble drug in deionized water to obtain an aqueous solution of the drug with a concentration of 0.05-3mg/mL; disperse n-HA in deionized water and disperse it evenly by ultrasonic to obtain n-HA with a concentration of 1-3mg/mL -HA suspension;

(2) under stirring, the aqueous solution of the above-mentioned medicine is added dropwise in the above-mentioned n-HA suspension, with the help of magnetic stirring, the AMX drug molecules are adsorbed on the surface of n-HA by surface physical adsorption; centrifugation to obtain precipitation, The precipitate was washed with deionized water, freeze-dried and filtered to obtain drug-loaded n-HA;

(3) ultrasonically disperse the above drug-loaded n-HA in a THF/DMF mixed solvent, add polylactic-co-glycolic acid (PLGA) to make a spinning solution, and then perform electrospinning, The n-HA/PLGA electrospun composite nanofiber drug-loading system was obtained.

The drug described in step (1) is amoxicillin (AMX).

In step (1), the concentration of the aqueous solution of the drug is 2 mg/mL, the concentration of the n-HA suspension is 1 mg/mL, the mass ratio of the water-soluble drug to n-HA is 2:1, and the ultrasonic dispersion time is 30 to 50 min .

When adding dropwise as described in step (2), the drop rate of the aqueous solution of the drug is controlled at 3 to 5 mL/min, the stirring time is 18 to 24 hours, and the rotation speed is such that the suspension does not precipitate.

The centrifugal speed of the centrifugation in step (2) is 4000-6000 rpm, and the time is 3-5 minutes; the number of times of washing the precipitate is 2-3 times.

The filtration described in step (2) is to use 325 mesh screens to filter.

The volume ratio of THF to DMF in the THF/DMF mixed solvent described in step (3) is 3:1; the time for ultrasonic dispersion is 3-5 minutes.

The ratio of the mass of PLGA added in step (3) to the volume of the THF/DMF mixed solvent is 1 g: 4-5 mL.

The process conditions of the electrospinning described in the step (3) are: the receiving distance is 10-20 cm, the voltage is 15-25 kV, and the flow rate is 0.8-1 mL/h.

The present invention characterizes the feasibility of preparing the n-HA/PLGA dual-carrier nano drug controlled release system containing n-HA by using scanning electron microscope (SEM), mechanical performance test, transmission electron microscope (TEM) and the like. In addition, the present invention also evaluates the slow release kinetics and antibacterial activity in vitro of the drug controlled release system. The specific test results are as follows:

(1) Optimization results of n-HA loading drug AMX conditions

It can be seen from Figure 1 of the description that the drug load increases with the increase of the drug concentration, but decreases with the increase of the carrier concentration. Because the AMX concentration is too high and the dissolution is not sufficient, the concentration of AMX is selected as 2mg/ mL, the concentration of n-HA was 1 mg/mL, the mass ratio of AMX to n-HA was 2:1, and the optimal maximum drug loading rate was 20.44%.

(2) TEM characterization results of n-HA nanopowder and AMX/n-HA/PLGA composite nanofiber

It can be seen from the accompanying drawing 2 (a) of the specification that n-HA is a rod-like structure with a width of 37±9nm and a length of 118±42nm. It can also be seen from the accompanying drawing 2(b) of the specification that n-HA is well wrapped in Electrospinning of PLGA nanofibers.

(3) SEM characterization results of electrospun AMX/n-HA/PLGA composite nanofiber drug-loading system

The PLGA nanofibers prepared by electrospinning and the composite nanofibers of n-HA/PLGA, AMX/PLGA and AMX/n-HA/PLGA are smooth and uniform, and there is no obvious adhesion between the fibers. b, c, d. The nanofiber mats all have a large pore structure, the porosity is 71.5%, 71.4%, 75.1% and 74.8%, respectively, and the average diameter of the fiber is 656±161nm, 636±152nm, 777±202nm and 620±107nm. After adding n-HA, the porosity of the fiber mat does not change much, and the diameter of the fiber becomes slightly smaller. According to the literature, due to the presence of hydroxyl groups on the surface of nano-hydroxyapatite, the surface charge density of the charged jet increases under the action of a high-voltage electrostatic field. It is conducive to the stretching and thinning of the fiber, so that the diameter of the fiber becomes smaller. The diameter of AMX/PLGA nanofibers increased, mainly because the addition of AMX caused changes in the properties of the PLGA spinning solution (such as electrical conductivity, viscosity, etc.).

(4) Stress-strain curves of electrospun AMX/n-HA/PLGA composite nanofiber drug-loaded system

Stress-strain curves of electrospun 25% PLGA, n-HA/PLGA (n-HA is 5% by mass of PLGA) and AMX/n-HA/PLGA (AMX is 1% by mass of PLGA) nanofiber mats, see attached Figure 4. It can be seen from the stress-strain curve that the fracture strength and initial modulus of the composite nanofiber mat containing n-HA and AMX/n-HA are improved compared with pure PLGA nanofibers, and the mechanical properties are improved.

(5) Drug release kinetics of electrospun AMX/n-HA/PLGA composite nanofiber drug-loaded system

The release kinetics curves of nanofiber drug-loaded systems were compared with those of AMX/n-HA powder and AMX/PLGA blended, see Figure 5. Compared with AMX/n-HA powder and AMX/PLGA blended nanofiber drug-loaded system, the electrospun AMX/n-HA/PLGA nanofiber dual-carrier drug-loaded system has no obvious "burst release" phenomenon, and the drug can last released.

(6) In vitro antibacterial activity of electrospun AMX/n-HA/PLGA composite nanofiber drug-loaded system

The in vitro dynamic and static antibacterial activity tests of the electrospun AMX/n-HA/PLGA composite nanofiber drug-carrying system were respectively carried out, and the results are shown in Figure 6 and Figure 7 of the description, respectively. The results of antibacterial experiments show that the electrospun AMX/n-HA/PLGA composite nanofiber drug-loading system can play a very good antibacterial effect.

Beneficial effect

(1) The preparation method of the present invention is simple, easy to operate, the polymer used has good biocompatibility, and PLGA and n-HA are suitable for mass production;

(2) the fiber mat containing n-HA prepared by the inventive method has obvious improvement in its mechanical strength;

(3) The n-HA/PLGA dual-carrier drug-loading system prepared by the method of the present invention has a good sustained drug release effect.

Description of drawings

Fig. 1 is the condition optimization diagram of the n-HA loaded drug AMX used in the present invention;

Fig. 2 is the TEM figure of n-HA nanoparticle (a), n-HA/PLGA nanofiber (b) and PLGA nanofiber (c) used in the present invention;

Fig. 3 is the electrospinning PLGA nanofiber SEM figure (a) that the present invention prepares, the SEM figure (b) of electrospinning n-HA/PLGA composite nanofiber, the SEM figure (c) of electrospinning AMX/PLGA composite nanofiber and SEM image (d) of electrospun AMX/n-HA/PLGA composite nanofibers;

Fig. 4 is the stress-strain curve of electrospinning PLGA, n-HA/PLGA and AMX/n-HA/PLGA nanofiber prepared by the present invention;

Fig. 5 is the drug release kinetics curve of AMX/n-HA nanopowder, AMX/PLGA blended fiber and AMX/n-HA/PLGA composite nanofiber drug-carrying system prepared by the present invention;

Fig. 6 is the liquid bacteriostatic activity control figure of the AMX/n-HA/PLGA nanofiber mat prepared by the present invention;

Fig. 7 is the solid plate antibacterial activity contrast of the electrospun AMX/n-HA/PLGA nanofiber mat prepared by the present invention

Figure; where 1, 2, 3, 4 represent PLGA, n-HA/PLGA, AMX/PLGA, AMX/n-HA/PLGA nanofiber mats, a, b, c, d are Staphylococcus aureus lawns The topography of the inhibition zone of the four nanofiber mats taken at each time point of culture 6h, 12h, 18h, and 24h.

Detailed ways

Below in conjunction with specific embodiment, further illustrate the present invention. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the teachings of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Example 1

Dissolve or disperse 40mg AMX and 20mg n-HA in deionized water respectively, and ultrasonically disperse the n-HA suspension for 30-50 minutes;

Add the AMX solution dropwise to the n-HA suspension, the dropping rate is controlled at 3mL/min, the final mass ratio of the two is 2:1, and the prepared mixed solution is stirred for 18-24h, and the speed is so that the suspension does not precipitate can;

Transfer the resulting mixture to a centrifuge tube, centrifuge at 3000-5000rpm for 3-5min, take out the supernatant, wash the n-HA precipitate loaded with AMX with deionized water for 3-5 times, wash the supernatant with The solution was mixed for use; the AMX/n-HA precipitate was dried in a freeze dryer at low temperature for 18-24 hours, the dried powder was ground with an agate mortar, and then filtered with a 325-mesh sieve for use.

Example 2

The supernatant obtained by centrifugation in Example 1 and the washing solution are diluted 20 times, and the absorbance of the AMX solution at 228nm is tested with a UV spectrophotometer. According to the concentration-absorbance relationship curve calibrated with the AMX solution in advance, the n- Calculate the average drug-loading efficiency (drug-loading efficiency (%)=mass of n-HA loaded AMX/mass of n-HA) based on the amount of AMX remaining in the solution after HA is loaded. According to accompanying drawing 1 result, the concentration of choosing AMX is 2mg/mL, and the concentration of n-HA is 1mg/mL, and the mass ratio of AMX and n-HA is 2: 1, has prepared the AMX/ n-HA nanopowder.

Example 3

Add 26 mg of n-HA powder with a drug loading efficiency of 19.2% obtained in Example 1 into 2 mL of THF/DMF (3:1) solvent, ultrasonically disperse for 3-5 min, stir for 30-50 min, and add 0.5 g of PLGA Dissolve in the above mixed solution, stir for 8h, and prepare a homogeneous electrospinning solution with a mass percent concentration of 1% (AMX relative to PLGA is 1wt%), and then prepare a nanofiber felt according to a conventional electrospinning method, wherein the receiving distance 15cm, the voltage is 20kV, and the flow rate is 0.8mL/h. The prepared composite nanofiber mat is dried in a vacuum oven for 48h to remove the residual solvent and is ready for use.

TEM characterization results (as shown in Figure 2a) show that n-HA is a rod-like structure with a width of 37 ± 9nm and a length of 118 ± 42nm. It can also be seen that n-HA is well wrapped in electrospun PLGA nanofibers ( As shown in accompanying drawing 2b), and the pure PLGA nanofiber prepared in comparative example 1 does not show the nanorod-like structure wrapped inside (as shown in accompanying drawing 2c). The SEM characterization results (as shown in accompanying drawing 3a, b, c, d) of nanofiber mat show that PLGA (see comparative example 1), n-HA/PLGA (see comparative example 2), AMX/PLGA prepared by the present invention (See Comparative Example 3), AMX/n-HA/PLGA nanofibers have regular morphology and regular surface, and all have larger pore structures, with porosities of 71.5%, 71.4%, 75.1% and 74.8%, respectively, and fiber diameters 656±161nm, 636±152nm, 777±202nm and 620±107nm. Obviously, when a certain amount of n-HA nanoparticles is doped in the PLGA spinning solution, under the same spinning conditions, the diameter of the obtained nanofibers decreases. According to the literature, due to the surface of nano-hydroxyapatite The presence of hydroxyl groups increases the surface charge density of the charged jet under the action of a high-voltage electrostatic field, which is conducive to the stretching and thinning of the fiber, making the diameter of the fiber smaller. The diameter of AMX/PLGA nanofibers increased, mainly because the addition of AMX caused changes in the properties of the PLGA spinning solution (such as electrical conductivity, viscosity, etc.).

Example 4

The electrospinning PLGA (25%, w/v) that comparative example 1 prepares, the electrospinning n-HA (relative PLGA 5wt%)/PLGA that comparative example 2 prepares and the AMX (relative PLGA 1wt%) that embodiment 3 prepares/ The n-HA/PLGA nanofiber mat was cut into 10×50 strips, each sample had 5 parallel samples, and the thickness of five different positions of each fiber mat was measured with a micrometer, and the average value was calculated. The mechanical properties of the fiber mat were tested with a universal material testing machine, and the stress-strain curve, breaking strength and breaking elongation were obtained. It can be seen from accompanying drawing 4 that the breaking strength of n-HA/PLGA and AMX/n-HA/PLGA composite nanofiber mats is increased by the addition of n-HA, which fully demonstrates that n-HA is a good fiber reinforcement body.

Example 5

Take 100 mg of the electrospun AMX/n-HA/PLGA composite nanofiber mat obtained in Example 3, and place it in a reagent bottle containing 10 mL of PBS buffer solution for sustained release experiments. The same method takes the 100mgAMX prepared in Comparative Example 3 (relative to PLGA 1wt%)/PLGA composite nanofiber felt and the 5.2mgAMX/n-HA nanometer powder prepared in Example 2 as a contrast.

Place the reagent bottle in a shaker at 37°C and shake it. At different time points, 1.5 mL of the solution is taken out of the reagent bottle, and then supplemented with 1.5 mL of PBS buffer. The concentration of the taken-out sustained-release solution was tested with a UV spectrophotometer, and the concentration-absorbance calibration curve of AMX in PBS was used to calculate the sustained-release percentage at different time points and analyze the drug release kinetics of the n-HA/PLGA dual-carrier drug-loaded system feature. As can be seen from Figure 5, compared with AMX/n-HA powder and AMX/PLGA blended nanofiber drug-loaded system, the electrospun AMX/n-HA/PLGA nanofiber dual-carrier drug-loaded system has no obvious "shock". "release" phenomenon, and the drug can be released continuously.

Example 6

Get the electrospun AMX/n-HA/PLGA composite nanofiber mat that obtains in 30mg embodiment 3 and the comparative example material of identical quality and contrast material (note that the material containing medicine refers to the same drug content, and the carrier material without medicine refers to carrier quality is the same), including raw material n-HA nanoparticles, antibacterial drug AMX, the AMX/n-HA nanopowder prepared in Example 2, the PLGA nanofiber prepared in Comparative Example 1, the n-HA/PLGA nanometer prepared in Comparative Example 2 Fiber and the AMX/PLGA nanofiber prepared in Comparative Example 3. Place it in a test tube equipped with 5mL beef extract peptone medium for in vitro dynamic bacteriostatic test.

Add the 6h UV-sterilized fiber mat to the pre-high-pressure steam sterilized medium, and inoculate Staphylococcus aureus with an absorbance of 0.1-0.2 at 625nm, and culture it in a constant temperature shaking incubator at 37°C for 24h. Measure the absorbance at 625nm and calculate the antibacterial rate (inhibition rate=(absorbance value of control group−absorbance value of experimental group)/absorbance value of control group).

It can be seen from Figure 6 that, compared with the comparative material and the control group, the electrospun AMX/n-HA/PLGA nanofiber dual-carrier drug-loading system showed antibacterial activity, but AMX/n-HA did not show significant The reason may be that n-HA itself is a good adsorption carrier for proteins. The beef extract and peptone in the medium are adsorbed on the surface of n-HA, covering the drug molecules, so that they cannot be released well and show Bacteriostatic activity.

Example 7

Get the electrospun AMX/n-HA/PLGA composite nanofiber mat that obtains in embodiment 3 and the PLGA nanofiber prepared by comparative example 1, the n-HA/PLGA nanofiber prepared by contrast 2, the AMX/PLGA prepared by comparative example 3 The nanofiber mat is prepared with a hole puncher with an inner diameter of 1 cm to prepare a round fiber mat, which is placed on a solid medium plate coated with Staphylococcus aureus for static bacteriostatic test in vitro.

Paste the round fiber mat treated with ultraviolet sterilization for 6 hours on a solid medium plate coated with 200 μL of Staphylococcus aureus, and culture it in a constant temperature shaking incubator at 37°C. Take pictures at 6, 12, 18, and 24 hours to observe the antibacterial effect Changes in the circle to verify the release effect of the sustained-release system. As can be seen from accompanying drawing 7, AMX/PLGA (3), AMX/n-HA/PLGA (4) composite nanofiber felt compared with PLGA (1), n-HA/PLGA (2) all appeared obvious Antibacterial zone, showing a good antibacterial effect.

Comparative example 1

0.5g of PLGA was dissolved in 2ml of THF/DMF (3:1) solvent, prepared into a solution with a mass concentration percentage of 25%, left to stand overnight, prepared into a uniform transparent electrospinning solution, and then according to conventional electrospinning The method for preparing nanofiber mats, wherein the spinning conditions were consistent with those in Example 3, and the prepared PLGA nanofiber mats were dried in a vacuum drying oven for 48 hours to remove residual solvents and were ready for use. It can be seen from accompanying drawing 3a that the PLGA nanofibers prepared by the present invention have regular appearance, regular surface, large pore structure, porosity of 71.5%, and fiber diameter of 656±161nm.

Comparative example 2

Add 25mg of n-HA nanopowder into 2mL of THF/DMF (3:1) solvent, ultrasonically disperse for 30-60min, dissolve 0.5g of PLGA in the above mixture, stir for 8h, and prepare a concentration of 5% by mass. % (n-HA relative to PLGA is 5wt%) uniform electrospinning solution, and then prepare nanofiber felt according to the conventional electrospinning method, wherein the spinning conditions are consistent with those in Example 3. The prepared n-HA/PLGA composite nanofiber mat was dried in a vacuum drying oven for 48 hours to remove residual solvent, and then used. It can be seen from Figure 3b that the n-HA/PLGA nanofibers prepared by the present invention have regular morphology, regular surface, large pore structure, porosity of 71.4%, and fiber diameter of 636±152nm.

Comparative example 3

5mg AMX is dissolved in the THF/DMF (3: 1) solvent of 2mL, the PLGA of 0.5g is dissolved in the above-mentioned solution, stir 8h, be prepared into the homogeneous solution that mass percent concentration is 1% (AMX is 1wt% relative to PLGA). Electrospinning liquid, then prepare nanofiber felt according to the method for routine electrospinning, wherein spinning condition is consistent with embodiment 3, the AMX/PLGA composite nanofiber felt of preparation is dried 48h in vacuum oven to remove residual Solvent, ready to use. It can be seen from accompanying drawing 3c that the AMX/PLGA nanofiber diameter distribution range prepared by the present invention is slightly larger, but does not affect its pore structure and fiber morphology, the porosity is 75.1%, and the fiber diameter is 777±202nm.

Claims (9)

1. a n-HA/PLGA static spins the method for preparing of composite nano fiber medicine-carried system, comprising:

(1) water soluble drug is dissolved in the deionized water, getting concentration is the aqueous solution of the medicine of 0.05-3mg/mL; N-HA is dispersed in the deionized water, and ultra-sonic dispersion is even, and getting concentration is the n-HA suspension of 1-3mg/mL;

(2) stir down, the aqueous solution of said medicine is dropwise added in said n-HA suspension; Centrifugalize must precipitate, and with the deionized water wash deposition, lyophilization is also filtered, and obtains the n-HA of carrying medicament;

(3) with the n-HA ultra-sonic dispersion of above-mentioned carrying medicament in the THF/DMF mixed solvent, add polylactic acid-glycolic guanidine-acetic acid PLGA and be made into spinning solution, carry out electrostatic spinning then, obtain n-HA/PLGA static and spin the composite nano fiber medicine-carried system.

2. a kind of n-HA/PLGA static according to claim 1 spins the method for preparing of composite nano fiber medicine-carried system, it is characterized in that: the medicine described in the step (1) is amoxicillin AMX.

3. a kind of n-HA/PLGA static according to claim 1 spins the method for preparing of composite nano fiber medicine-carried system; It is characterized in that: the concentration of the aqueous solution of step (1) Chinese medicine is 2mg/mL; The concentration of n-HA suspension is 1mg/mL; The mass ratio of water soluble drug and n-HA is 2: 1, and the ultra-sonic dispersion time is 30～50min.

4. a kind of n-HA/PLGA static according to claim 1 spins the method for preparing of composite nano fiber medicine-carried system; It is characterized in that: dropwise adding described in the step (2) is fashionable; The rate of addition of the aqueous solution of medicine is controlled at 3～5mL/min, and mixing time is 18～24h.

5. a kind of n-HA/PLGA static according to claim 1 spins the method for preparing of composite nano fiber medicine-carried system, it is characterized in that: the centrifugal speed of the centrifugalize described in the step (2) is 4000～6000rpm, and the time is 3～5min; The washing times of described washing precipitation is 2～3 times.

6. a kind of n-HA/PLGA static according to claim 1 spins the method for preparing of composite nano fiber medicine-carried system, it is characterized in that: being filtered into described in the step (2) used 325 purpose screen filtrations.

7. a kind of n-HA/PLGA static according to claim 1 spins the method for preparing of composite nano fiber medicine-carried system, it is characterized in that: the volume ratio of THF and DMF is 3: 1 in the THF/DMF mixed solvent described in the step (3); The time of ultra-sonic dispersion is 3～5min.

8. a kind of n-HA/PLGA static according to claim 1 spins the method for preparing of composite nano fiber medicine-carried system, it is characterized in that: the quality of the PLGA that is added in the step (3) is 1g: 4-5mL with the ratio of the volume of THF/DMF mixed solvent.

9. a kind of n-HA/PLGA static according to claim 1 spins the method for preparing of composite nano fiber medicine-carried system; It is characterized in that: the process conditions of the electrostatic spinning described in the step (3) are: receiving range is 10～20cm; Voltage is 15～25kV, and flow velocity is 0.8～1mL/h.

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