FIBROUS MEMBRANE MATERIAL FOR SOFT TISSUE REPAIR, METHOD FOR PREPARING THE SAME, AND APPLICATION THEREOF

Abstract

A fibrous membrane material includes a biodegradable polymer fiber and an active material dispersed in the biodegradable polymer fiber.

Claims

1. A fibrous membrane material for soft tissue repair, comprising a biodegradable polymer fiber and an active material dispersed in the biodegradable polymer fiber.

2. The fibrous membrane material of claim 1, wherein the biodegradable polymer fiber has a diameter of 0.1-3 μm; and the biodegradable polymer fiber has a porosity of 65-90%.

3. The fibrous membrane material of claim 1, wherein the biodegradable polymer fiber comprises a biodegradable polymer selected from the group consisting of polylactic acid (PLA), poly(lactic-co-glycolic acid) copolymer, polyethylene glycol (PEG), poly(p-dioxanone), polycaprolactone, poly(L-lactide-co-caprolactone), a triblock copolymer PLA-b-PEG-b-PLA, and a combination thereof.

4. The fibrous membrane material of claim 2, wherein the biodegradable polymer fiber comprises a biodegradable polymer selected from the group consisting of polylactic acid (PLA), poly(lactic-co-glycolic acid) copolymer, polyethylene glycol (PEG), poly(p-dioxanone), polycaprolactone, poly(L-lactide-co-caprolactone), a triblock copolymer PLA-b-PEG-b-PLA, and a combination thereof.

5. The fibrous membrane material of claim 3, wherein: a number average molecular weight of the polylactic acid is 8000-70000 Da; a number average molecular weight of the poly(lactic-co-glycolic acid) copolymer is 40000-100000 Da; a number average molecular weight of the polyethylene glycol is 1000-20000 Da; a number average molecular weight of the poly(p-dioxanone) is 60000-250000 Da; a number average molecular weight of the polycaprolactone is 6000-100,000 Da; a molar ratio of lactide units to caprolactone units of the poly(L-lactide-co-caprolactone) is between 1:99 and 50:50, and an average molecular weight of the poly(L-lactide-co-caprolactone) is 35000-85000 Da; and an average molecular weight of the triblock copolymer PLA-b-PEG-b-PLA is 60000-100000 Da.

6. The fibrous membrane material of claim 4, wherein: a number average molecular weight of the polylactic acid is 8000-70000 Da; a number average molecular weight of the poly(lactic-co-glycolic acid) copolymer is 40000-100000 Da; a number average molecular weight of the polyethylene glycol is 1000-20000 Da; a number average molecular weight of the poly(p-dioxanone) is 60000-250000 Da; a number average molecular weight of the polycaprolactone is 6000-100,000 Da; a molar ratio of lactide units to caprolactone units of the poly(L-lactide-co-caprolactone) is between 1:99 and 50:50, and an average molecular weight of the poly(L-lactide-co-caprolactone) is 35000-85000 Da; and an average molecular weight of the triblock copolymer PLA-b-PEG-b-PLA is 60000-100000 Da.

7. The fibrous membrane material of claim 3, wherein in a combination of the poly(lactic-co-glycolic acid) copolymer and the polycaprolactone, a mass ratio of the poly(lactic-co-glycolic acid) copolymer to the polycaprolactone is between 1:99 and 99:1.

8. The fibrous membrane material of claim 4, wherein in a combination of the poly(lactic-co-glycolic acid) copolymer and the polycaprolactone, a mass ratio of the poly(lactic-co-glycolic acid) copolymer to the polycaprolactone is between 1:99 and 99:1.

9. The fibrous membrane material of claim 7, wherein in a combination of the poly(lactic-co-glycolic acid) copolymer and the polycaprolactone, a mass ratio of the poly(lactic-co-glycolic acid) copolymer to the polycaprolactone is between 1:1 and 2:1.

10. The fibrous membrane material of claim 8, wherein in a combination of the poly(lactic-co-glycolic acid) copolymer and the polycaprolactone, a mass ratio of the poly(lactic-co-glycolic acid) copolymer to the polycaprolactone is between 1:1 and 2:1.

11. The fibrous membrane material of claim 1, wherein the active material comprises gelatin, an epidermal growth factor, a drug, or a combination thereof; the drug comprises ciprofloxacin, ciprofloxacin hydrochloride, moxifloxacin, levofloxacin, cefradine, tinidazole, 5-fluorouracil, doxorubicin, cis-platinum, taxol, gemcitabine, capecitabine, or a combination thereof; the drug accounts for 1-50 wt. % of the biodegradable polymer fiber; and the gelatin or the epidermal growth factor accounts for 1-10 wt. % of the biodegradable polymer fiber.

12. A method for preparing the fibrous membrane material for soft tissue repair of claim 1, the method comprising: (1) mixing a biodegradable polymer and the active material in a solvent to obtain a mixed solution; and (2) taking a part of the mixed solution in (1), and introducing the part of the mixed solution to a single-nozzle or multi-nozzle electrostatic spinning apparatus for electrostatic spinning, to obtain the fibrous membrane material for soft tissue repair.

13. The method of claim 12, wherein the solvent is N,N-dimethylformamide, acetone, hexafluoroisopropanol, or a combination thereof; in (1), the biodegradable polymer and the active material are mixed in the solvent at 35-50° C. under stirring; in (2), an inner diameter of a nozzle of the single-nozzle or multi-nozzle electrostatic spinning apparatus is 0.2-0.8 mm; a voltage during electrostatic spinning is 10-25 kV; a spinning distance during the electrostatic spinning is 5-15 cm; a temperature for the electrostatic spinning is 20-30° C.; an advancing speed of the mixed solution during the electrostatic spinning is 0.2-4 mL/L; and a receiving device during the electrostatic spinning is a metal drum with a diameter of 5-15 cm, and a rotation speed of the metal drum is 600-900 rpm.

14. The method of claim 12, wherein after 2), the fibrous membrane material for soft tissue repair is vacuum-dried at 20-30° C. for 24-72 h.

15. The method of claim 13, wherein after 2), the fibrous membrane material for soft tissue repair is vacuum-dried at 20-30° C. for 24-72 h.

16. A method for preparing a drug delivery system for soft tissue repair, the method comprising applying the fibrous membrane material for soft tissue repair of claim 1.

Description

BRIEF DESCRIPTION OF THE DIAGRAMS

[0054] FIG. 1 is a scanning electron microscope (SEM) diagram of a fibrous membrane prepared in Example 1;

[0055] FIG. 2 is an SEM diagram of a fibrous membrane with a mass ratio of the poly(lactic-co-glycolic acid) copolymer to polycaprolactone of 2:1 in Example 7;

[0056] FIG. 3 is an SEM diagram of a fibrous membrane with a mass ratio of the poly(lactic-co-glycolic acid) copolymer to polycaprolactone of 3:1 in Example 7;

[0057] FIG. 4 is cell morphology diagrams of three fibrous membranes prepared in Example 1 and Example 7 for fibroblast culture;

[0058] FIG. 5 is cell morphology diagrams of two fibrous membranes prepared in Example 1 and Example 2 for fibroblast culture;

[0059] FIG. 6 is cell morphology diagrams of five fibrous membranes prepared in Example 1 and Example 3-6 for fibroblast culture;

[0060] FIG. 7 is cell morphology diagrams of three fibrous membranes prepared in Example 1 and Examples 8-9 for fibroblast culture;

[0061] FIG. 8 is cell morphology diagrams of two fibrous membranes prepared in Example 1 and Example 10 for fibroblast culture;

[0062] FIG. 9 is a drug release curve of a fibrous membrane material prepared in Example 11;

[0063] FIG. 10 is a drug release curve of a fibrous membrane material prepared in Example 12; and

[0064] FIG. 11 is a drug release curve of a fibrous membrane material prepared in Example 13.

DESCRIPTION OF THE INVENTION

[0065] To further illustrate, embodiments detailing a fibrous membrane material, a method for preparing the same, and application thereof are described below. It should be noted that the following embodiments are intended to describe and not to limit the disclosure.

[0066] Example 1

[0067] The disclosure provided a fibrous membrane material for soft tissue repair, comprising a biodegradable polymer (poly(lactic-co-glycolic acid) copolymer (80000 Da) and polycaprolactone (60000 Da) mixed at a mass ratio of 1:1) fiber and an active material of gelatin dispersed therein. The biodegradable polymer fiber had a diameter of 0.75 μm and a porosity of 85%. The mass of the gelatin was 5% of the total mass of the biodegradable polymer fiber. Porosity=(1−p0/p)×100%; where p0 is apparent density of fibrous membrane, p is the density of polymer raw material.

[0068] A method for preparing the fibrous membrane material for soft tissue repair was as follows:

[0069] (1) stirring and mixing gelatin, poly(lactic-co-glycolic acid) copolymer and N,N-dimethylformamide at 40° C., and then stirring and mixing gelatin, polycaprolactone and N,N-dimethylformamide at 40° C. to obtain two mixed solutions;

[0070] (2) mixing and loading the two mixed solutions in (1) into a 22G syringe, introducing the two mixed solutions to a single-nozzle electrostatic spinning apparatus for electrostatic spinning at 25° C., where the inner diameter of a nozzle was 0.4 mm; the advancing speed of the solution was 0.8 mL/h; the spinning voltage was 15 kV; the spinning distance was 10 cm; a receiving device was a metal drum with a diameter of 10 cm, and the rotation speed was 800 rpm to obtain the fibrous membrane material for soft tissue repair; and

[0071] (3) vacuum-drying the fibrous membrane material for soft tissue repair in (2) at 25° C. for 48 h.

Example 2

[0072] The disclosure provided a fibrous membrane material for soft tissue repair, comprising a biodegradable polymer (poly(lactic-co-glycolic acid) copolymer (80000 Da) and polycaprolactone (60000 Da) mixed at a mass ratio of 1:1) fiber and an active material of gelatin dispersed therein. The biodegradable polymer fiber had a diameter of 0.75 μm and a porosity of 85%. The mass of the gelatin was 5% of the total mass of the biodegradable polymer fiber.

[0073] A method for preparing the fibrous membrane material for soft tissue repair was as follows:

[0074] (1) stirring and mixing gelatin, poly(lactic-co-glycolic acid) copolymer and N,N-dimethylformamide at 40° C., and then stirring and mixing gelatin, polycaprolactone and N,N-dimethylformamide at 40° C. to obtain two mixed solutions;

[0075] (2) separately loading the two mixed solutions in (1) into 22G syringes, introducing the two mixed solutions to a double-nozzle electrostatic spinning apparatus for electrostatic spinning at 25° C., where the inner diameter of a nozzle was 0.4 mm; the advancing speed of the solution was 0.8 mL/h; the spinning voltage was 18 kV; the spinning distance was 15 cm; a receiving device was a metal drum with a diameter of 10 cm, and the rotation speed was 900 rpm to obtain the fibrous membrane material for soft tissue repair; and

[0076] (3) vacuum-drying the fibrous membrane material for soft tissue repair in (2) at 25° C. for 48 h.

Example 3

[0077] The disclosure provided a fibrous membrane material for soft tissue repair, comprising a biodegradable polymer (poly(lactic-co-glycolic acid) copolymer (80000 Da) and polycaprolactone (60000 Da) mixed at a mass ratio of 1:1) fiber and an active material of gelatin dispersed therein. The biodegradable polymer fiber had a diameter of 2.5 μm and a porosity of 65.5%. The mass of the gelatin was 5% of the total mass of the biodegradable polymer fiber.

[0078] A method for preparing the fibrous membrane material for soft tissue repair was as follows:

[0079] (1) stirring and mixing gelatin, poly(lactic-co-glycolic acid) copolymer and N,N-dimethylformamide at 40° C., and then stirring and mixing gelatin, polycaprolactone and N,N-dimethylformamide at 40° C. to obtain two mixed solutions;

[0080] (2) separately loading the two mixed solutions in (1) into 22G syringes, introducing the two mixed solutions to a double-nozzle electrostatic spinning apparatus for electrostatic spinning at 25° C., where the inner diameter of a nozzle was 0.6 mm; the advancing speed of the solution was 0.8 mL/h; the spinning voltage was 13 kV; the spinning distance was 8 cm; a receiving device was a metal drum with a diameter of 10 cm, and the rotation speed was 650 rpm to obtain the fibrous membrane material for soft tissue repair; and

[0081] (3) vacuum-drying the fibrous membrane material for soft tissue repair in (2) at 25° C. for 48 h.

Example 4

[0082] The disclosure provided a fibrous membrane material for soft tissue repair, comprising a biodegradable polymer (poly(lactic-co-glycolic acid) copolymer (80000 Da) and polycaprolactone (60000 Da) mixed at a mass ratio of 1:1) fiber and an active material of gelatin dispersed therein. The biodegradable polymer fiber had a diameter of 0.5 μm and a porosity of 89%. The mass of the gelatin was 5% of the total mass of the biodegradable polymer fiber.

[0083] A method for preparing the fibrous membrane material for soft tissue repair was as follows:

[0084] (1) stirring and mixing gelatin, poly(lactic-co-glycolic acid) copolymer and N,N-dimethylformamide at 40° C., and then stirring and mixing gelatin, polycaprolactone and N,N-dimethylformamide at 40° C. to obtain two mixed solutions;

[0085] (2) separately loading the two mixed solutions in (1) into 22G syringes, introducing the two mixed solutions to a double-nozzle electrostatic spinning apparatus for electrostatic spinning at 25° C., where the inner diameter of a nozzle was 0.35 mm; the advancing speed of the solution was 0.8 mL/h; the spinning voltage was 18 kV; the spinning distance was 15 cm; a receiving device was a metal drum with a diameter of 10 cm, and the rotation speed was 850 rpm to obtain the fibrous membrane material for soft tissue repair; and

[0086] (3) vacuum-drying the fibrous membrane material for soft tissue repair in (2) at 25° C. for 48 h.

Example 5

[0087] The disclosure provided a fibrous membrane material for soft tissue repair, comprising a biodegradable polymer (poly(lactic-co-glycolic acid) copolymer (80000 Da) and polycaprolactone (60000 Da) mixed at a mass ratio of 1:1) fiber and an active material of gelatin dispersed therein. The biodegradable polymer fiber had a diameter of 3.10 μm and a porosity of 64.3%. The mass of the gelatin was 5% of the total mass of the biodegradable polymer fiber.

[0088] Following the method of Example 1, the parameters for the electrostatic spinning were fine-tuned to prepare a polymer fiber having a diameter of 3.10 μm.

Example 6

[0089] The disclosure provided a fibrous membrane material for soft tissue repair, comprising a biodegradable polymer (poly(lactic-co-glycolic acid) copolymer (80000 Da) and polycaprolactone (60000 Da) mixed at a mass ratio of 1:1) fiber and an active material of gelatin dispersed therein. The biodegradable polymer fiber had a diameter of 0.05 μm and a porosity of 93.46%. The mass of the gelatin was 5% of the total mass of the biodegradable polymer fiber.

[0090] Following the method of Example 1, the parameters for the electrostatic spinning were fine-tuned to prepare a polymer fiber having a diameter of 0.05 um.

Example 7

[0091] The disclosure provided two fibrous membrane materials for soft tissue repair, comprising a biodegradable polymer (poly(lactic-co-glycolic acid) copolymer (80000 Da) and polycaprolactone (60000 Da) mixed at a mass ratio of 2:1 and 3:1, respectively) fiber and an active material of gelatin dispersed therein. The biodegradable polymer fiber had a diameter of 0.75 μm and a porosity of 84.55%. The mass of the gelatin was 5% of the total mass of the biodegradable polymer fiber.

[0092] Following the method of Example 1, the parameters for the electrostatic spinning were fine-tuned to prepare a polymer fiber having a diameter of 0.75 um.

Example 8

[0093] The disclosure provided a fibrous membrane material for soft tissue repair, comprising a biodegradable polymer (poly(lactic-co-glycolic acid) copolymer (80000 Da)) fiber and an active material of gelatin dispersed therein. The biodegradable polymer fiber had a diameter of 0.75 μm and a porosity of 85.12%. The mass of the gelatin was 5% of the total mass of the biodegradable polymer fiber.

[0094] Following the method of Example 1, the parameters for the electrostatic spinning were fine-tuned to prepare a polymer fiber having a diameter of 0.75 μm.

Example 9

[0095] The disclosure provided a fibrous membrane material for soft tissue repair, comprising a biodegradable polymer (polycaprolactone (60000 Da)) fiber and an active material of gelatin dispersed therein. The biodegradable polymer fiber had a diameter of 0.75 μm and a porosity of 85.33%. The mass of the gelatin was 5% of the total mass of the biodegradable polymer fiber.

[0096] Following the method of Example 1, the parameters for the electrostatic spinning were fine-tuned to prepare a polymer fiber having a diameter of 0.75

Example 10

[0097] The disclosure provided a fibrous membrane material for soft tissue repair, comprising a biodegradable polymer (poly(lactic-co-glycolic acid) copolymer (80000 Da) and polycaprolactone (60000 Da) mixed at a mass ratio of 1:1) fiber and an active material of gelatin dispersed therein. The biodegradable polymer fiber had a diameter of 0.75 μm and a porosity of 84.15%. The mass of the gelatin was 15% of the total mass of the biodegradable polymer fiber.

[0098] Following the method of Example 1, the parameters for the electrostatic spinning were fine-tuned to prepare a polymer fiber having a diameter of 0.75

Example 11

[0099] The disclosure provided three fibrous membrane materials for soft tissue repair, comprising a biodegradable polymer (poly(lactic-co-glycolic acid) copolymer (60000 Da)) fiber and an active material of paclitaxel dispersed therein. The biodegradable polymer fiber had a diameter of 0.75 μm and a porosity of 85%. In the three fibrous membrane materials, the mass of the paclitaxel was 5%, 10%, and 20% of the total mass of the biodegradable polymer fiber, respectively.

[0100] Following the method of Example 1, the parameters for the electrostatic spinning were fine-tuned to prepare a polymer fiber having a diameter of 0.75 μm.

Example 12

[0101] The disclosure provided a fibrous membrane material for soft tissue repair, comprising a biodegradable polymer (poly(lactic-co-glycolic acid) copolymer (60000 Da)) fiber and an active material of 5-fluorouracil dispersed therein. The biodegradable polymer fiber had a diameter of 0.75 μm and a porosity of 85%. The mass of the 5-fluorouracil was 10% of the total mass of the biodegradable polymer fiber.

[0102] Following the method of Example 1, the parameters for the electrostatic spinning were fine-tuned to prepare a polymer fiber having a diameter of 0.75 μm.

Example 13

[0103] The disclosure provided a fibrous membrane material for soft tissue repair, comprising a biodegradable polymer (poly(lactic-co-glycolic acid) copolymer (60000 Da)) fiber and an active material of cefradine dispersed therein. The biodegradable polymer fiber had a diameter of 0.75 μm and a porosity of 84.56%. The mass of the cefradine was 10% of the total mass of the biodegradable polymer fiber.

[0104] Following the method of Example 1, the parameters for the electrostatic spinning were fine-tuned to prepare a polymer fiber having a diameter of 0.75 μm.

[0105] Evaluating the test:

[0106] (1) SEM test:

[0107] The three fibrous membrane material for soft tissue repairs in Example 1 and Example 7 were scanned with an electron microscope, and results were shown in FIGS. 1-3 (FIG. 1 was the fibrous membrane prepared in Example 1; FIG. 2 was the fibrous membrane with a mass ratio of the poly(lactic-co-glycolic acid) copolymer to polycaprolactone of 2:1 in Example 7, and FIG. 3 was the fibrous membrane with a mass ratio of the poly(lactic-co-glycolic acid) copolymer to polycaprolactone of 3:1 in Example 7). It can be seen from FIGS. 1-3 that the fiber diameters with the three different mass rations of the poly(lactic-co-glycolic acid) copolymer to polycaprolactone were relatively uniform, and were basically maintained at about 0.75 um.

[0108] (2) Cell Culture Test:

[0109] 1. Performing fibroblast culture on the three fibrous membranes in Example 1 and Example 7, where the operation method was as follows: isolating Hs 865.Sk (ATCC-CRL-7601) cells on a culture plate with a protease enzymolysis method, centrifuging at 1000 rpm for 5 min, and adding a 10% (v/v) fetal bovine serum and a 1% (v/v) chloromycetin/streptomycin to a DMEM/F12 1:1 medium. Cells were suspended, planted and fixed in the membrane. The cells were cultured in the DMEM/F12 1:1 and the 10% fetal bovine serum (Hyclone) at 37° C. and 5% CO.sub.2 for 5 days, to produce proliferation and adhesion. The distribution of fibroblasts cultured on the fibrous membrane on the 1, 3, and 5 days after culture was shown in FIG. 4 (the cells were fluorescence-stained with a cell fluorescence staining method). In the soft tissue repair membranes with different ratios of the poly(lactic-co-glycolic acid) copolymer to polycaprolactone, the cells grew well with good morphology. The number of cells was gradually increased from the first day. In the repaired membranes with the mass ratio of the poly(lactic-co-glycolic acid) copolymer to polycaprolactone being 1:1 and 3:1, the cells grew well. However, the cells obviously contiguously grew, that is, the cell grew too fast, leading to tissue adhesion. In the repaired membrane with the ratio of 2:1, the cells had a tendency to grow fast, but not too fast. The cells grew stably without obvious contiguous growth and excessive proliferation. Therefore, the appropriate ratio of the poly(lactic-co-glycolic acid) copolymer to polycaprolactone is conducive to the normal growth of tissue cells.

[0110] 2. Performing the fibroblast culture on the two fibrous membranes in Example 1 and Example 2, where the operation method was as above. On the fifth day of culture, the distribution of the fibroblasts on the fibrous membrane was shown in FIG. 5 (the cells were fluorescence-stained with the cell fluorescence staining method). It could be seen from FIG. 5 that single-nozzle spinning cell culture results were better than double-nozzle spinning cell culture results. The morphology, size and number of the cells were all closer to the real growth of the cells.

[0111] 3. Performing the fibroblast culture on the two fibrous membranes in Example 1 and Examples 3-6, where the operation method was as above. On the fifth day of culture, the distribution of the fibroblasts on the fibrous membrane was shown in FIG. 6 (the cells were fluorescence-stained with the cell fluorescence staining method). It could be seen from FIG. 6 that when the diameter of the repaired membrane fibers was in the proper range (0.1-3 μm), the cells grew well. With an increase in the diameter, the number of the cells increased significantly, and the cell morphology grew well. Too fine fibers easily led to the aggregation of the cells, which is not conducive to the proliferation of the cells, resulting in too small cell number. However, too thick fibers result in a decline in the attachment of the cells, which is not conducive to the good morphology of the cells.

[0112] 4. Performing the fibroblast culture on the two fibrous membranes in Example 1 and Examples 8-9, where the operation method was as above. On the fifth day of culture, the distribution of the fibroblasts on the fibrous membrane was shown in FIG. 7 (the cells were fluorescence-stained with the cell fluorescence staining method). It could be seen from FIG. 7 that in poly(lactic-co-glycolic acid) copolymer, the cell grew best with good cell morphology. The cells were relatively dispersed and uniform, and mutually involved, which is conducive to the formation of new tissues. In pure poly(lactic-co-glycolic acid) copolymer, the cells were larger but scattered and independent without connection. In pure polycaprolactone, the number of cells was significantly reduced, and the cells are more scattered and independent, resulting in the poor effect of the tissue repair.

[0113] 5. Performing the fibroblast culture on the two fibrous membranes in Example 1 and Example 10, where the operation method was as above. On the fifth day of culture, the distribution of the fibroblasts on the fibrous membrane was shown in FIG. 8 (the cells were fluorescence-stained with the cell fluorescence staining method). It could be seen from FIG. 8 that in the repaired membranes with the mass ratio of the poly(lactic-co-glycolic acid) copolymer to polycaprolactone of 1:1, the cells cultured with the fibrous membrane with 5% of gelatin content had complete morphology and the larger number of cells. However, when the gelatin content was 15%, the number of cells decreased, and the cell morphology was obviously not as good as that of 5% cells due to the excessive gelatin content. The effect of the active material was basically not enhanced, but the attachment of the cells to the fibrous membrane was reduced, leading to adverse effect on the proliferation and differentiation of the cells.

[0114] (3) Drug release test:

[0115] The fibrous membranes in Examples 11-13 were tested with drug release to draw a release curve. The method was as follows:

[0116] (1) putting each fibrous membrane into a centrifuge tube containing 10 mL of a fresh PBS solution;

[0117] (2) putting the centrifuge tube into an air bath constant-temperature shaker at 37° C. with the speed of the shaker of 100 rpm, taking out 1 mL of the release solution and replenishing the same amount of the fresh PBS solution at a specified time interval;

[0118] (3) measuring 1 mL of the release solution with an ultraviolet-visible spectrophotometer, and determining the amount of the released drug according to a standard curve, where the results were measured in parallel for 5 times, and the measured drug release was expressed as an average value±standard deviation.

[0119] The results were shown in FIGS. 9-11 (FIG. 9 was the drug release curve of Example 11, FIG. 10 was the drug release curve of Example 12, and FIG. 11 was the drug release curve of Example 13).

[0120] FIG. 8 showed the release curve of taxol with different mass ratios. In the early stage of release, taxol maintained a low release rate. After a period of sustained release, the release rate accelerated and rose steadily. At the same time, with the increase of taxol, the gentle release cycle of taxol gradually decreased.

[0121] It could be seen from FIG. 9 that the release of 5-fluorouracil rose steadily at a constant rate in the early stage, and tended to be linear. After 90 h, the release rate of 5-fluorouracil began to gradually slow down until the drug release was complete.

[0122] It could be seen from FIG. 10 that the release cycle of cefradine was about 360 h. The release of cefradine tended to be flat in the early and late stages. At about 75 h, the release rate gradually increased, then began to be stable and fast, and gradually slowed down at about 230 h, and began to release slowly until the drug was completely released.

[0123] It will be obvious to those skilled in the art that changes and modifications may be made, and therefore, the aim in the appended claims is to cover all such changes and modifications.