NANO-OXIDE/KAOLIN COMPOSITE HEMOSTATIC ANTIBACTERIAL MATERIAL, HEMOSTATIC HEALING-PROMOTING DRESSING AND PREPARATION METHOD THEREOF

Abstract

The present invention belongs to the field of medical materials. A nano-oxide/kaolin composite hemostatic antibacterial material includes an iron oxide/kaolin composite carrier, and zinc oxide supported on the surface of the composite carrier. The present invention further provides the preparation and application of the composite hemostatic antibacterial material. Furthermore, the present invention provides a hemostatic healing-promoting dressing including the composite hemostatic antibacterial material disclosed by the present invention. The present invention surprisingly finds from research that the zinc oxide and iron oxide/kaolin composite carrier have a synergistic effect, and further cooperated with a special loading morphology, the synergistic effect of the two is unexpectedly enhanced, the hemostatic property and antibacterial property of the material are effectively improved, and moreover, the rate of wound healing is further improved.

Claims

1. A nano-oxide/kaolin composite hemostatic antibacterial material, comprising: an iron oxide/kaolin composite carrier; and zinc oxide supported on a surface of the iron oxide/kaolin composite carrier.

2. The nano-oxide/kaolin composite hemostatic antibacterial material according to claim 1, wherein the iron oxide/kaolin composite carrier is a homogeneous mixed material of iron oxide and kaolin, or a core-shell material with kaolin as a core and iron oxide as a shell.

3. The nano-oxide/kaolin composite hemostatic antibacterial material according to claim 1, wherein the nano-oxide/kaolin composite hemostatic antibacterial material has a particle size of 200-1000 nm; and the zinc oxide has a particle size of 10-100 nm.

4. The nano-oxide/kaolin composite hemostatic antibacterial material according to claim 1, wherein a weight percentage of the zinc oxide is 10%-50%; and a weight percentage of the iron oxide is 20-40%.

5. A preparation method of the nano-oxide/kaolin composite hemostatic antibacterial material according to claim 1, comprising forming zinc hydroxide in situ on the surface of the iron oxide/kaolin composite carrier by a precipitation method, and then performing calcination treatment.

6. The preparation method of the nano-oxide/kaolin composite hemostatic antibacterial material according to claim 5, further comprising: dispersing the iron oxide/kaolin composite carrier in water, adding a Zn source, and adjusting pH of a system to 10-11; and performing a precipitation reaction to deposit the zinc hydroxide in situ on the surface of the iron oxide/kaolin composite carrier.

7. The preparation method of the nano-oxide/kaolin composite hemostatic antibacterial material according to claim 6, wherein a concentration of zinc ions in a precipitation starting solution is not less than 0.001 mol/L.

8. The preparation method of the nano-oxide/kaolin composite hemostatic antibacterial material according to claim 7, wherein the concentration of zinc ions in the precipitation starting solution is 0.001-0.03 mol/L.

9. The preparation method of the nano-oxide/kaolin composite hemostatic antibacterial material according to claim 8, wherein the concentration of zinc ions in the precipitation starting solution is 0.008-0.015 mol/L.

10. The preparation method of the nano-oxide/kaolin composite hemostatic antibacterial material according to claim 6, wherein a temperature of the deposition reaction is 30-40 C.

11. The preparation method of the nano-oxide/kaolin composite hemostatic antibacterial material according to claim 6, wherein a calcination temperature is 250-550 C., and a calcination time is 2-4 h.

12. A preparation method of an external preparation having at least one of hemostatic, antibacterial, and wound healing promotion functions, comprising: using the nano-oxide/kaolin composite hemostatic antibacterial material according to claim 1.

13. The preparation method of the external preparation having at least one of hemostatic, antibacterial, and wound healing promotion functions according to claim 12, wherein the external preparation is at least one of an external powder preparation, paint or dressing.

14. A preparation method of an external preparation having at least one of hemostatic, antibacterial, and wound healing promotion functions, comprising: using the nano-oxide/kaolin composite hemostatic antibacterial material prepared by the preparation method according to claim 5.

15. A hemostatic healing-promoting dressing, comprising: a dressing substrate; and the nano-oxide/kaolin composite hemostatic antibacterial material according to claim 1, supported on the dressing substrate.

16. The hemostatic healing-promoting dressing according to claim 15, wherein the dressing substrate is at least one of a polymer fiber membrane and a hydrogel; and a weight content of the nano-oxide/kaolin composite hemostatic antibacterial material is 5%-20%.

17. A hemostatic healing-promoting dressing, comprising: a dressing substrate; and the nano-oxide/kaolin composite hemostatic antibacterial material prepared by the preparation method according to claim 5, supported on the dressing substrate.

18. A preparation method of a hemostatic healing-promoting fiber membrane containing a nano-oxide/kaolin composite, comprising: dissolving polycaprolactone and gelatin in a solvent; adding the nano-oxide/kaolin composite hemostatic antibacterial material according to claim 1; performing uniform mixing to obtain an electrostatic spinning solution; and performing electrostatic spinning on the electrostatic spinning solution to obtain the hemostatic healing-promoting fiber membrane containing the nano-oxide/kaolin composite.

19. The preparation method of the hemostatic healing-promoting fiber membrane containing the nano-oxide/kaolin composite according to claim 18, wherein in an electrostatic spinning process, the voltage of a tip and a collector is 15-25.0 kV, the distance is 15-30 cm, and the pushing speed is 0.003-0.01 mm/s.

20. A preparation method of a hemostatic healing-promoting fiber membrane containing a nano-oxide/kaolin composite, comprising: dissolving polycaprolactone and gelatin in a solvent; adding the nano-oxide/kaolin composite hemostatic antibacterial material prepared by the preparation method according to claim 5; performing uniform mixing to obtain an electrostatic spinning solution; and performing electrostatic spinning on the electrostatic spinning solution to obtain the hemostatic healing-promoting fiber membrane containing the nano-oxide/kaolin composite.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0059] FIG. 1 is a scanning electron micrograph of an iron oxide/kaolin composite with nano zinc oxide supported on the surface (labeled as ZnO/Kaolin@Fe.sub.2O.sub.3-3) prepared in Embodiment 4.

[0060] FIG. 2 is a transmission electron micrograph of the iron oxide/kaolin composite with nano zinc oxide supported on the surface (labeled as ZnO/Kaolin@Fe.sub.2O.sub.3-3) prepared in Embodiment 4.

[0061] FIG. 3 is a physical photograph of a hemostatic healing-promoting fiber membrane of ZnO/Kaolin@Fe.sub.2O.sub.3-3 (labeled as ZnO-Fe.sub.2O.sub.3-Kaolin-3/PG) prepared in Embodiment 5.

[0062] FIG. 4 is a scanning electron micrograph of the hemostatic healing-promoting fiber membrane of ZnO/Kaolin@Fe.sub.2O.sub.3-3 (labeled as ZnO/Kaolin@Fe.sub.2O.sub.3-3/PG) prepared in Embodiment 5.

DESCRIPTION OF THE EMBODIMENTS

[0063] To make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below with reference to accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present invention and are not intended to limit the present invention.

[0064] A hemostatic antibacterial material containing a zinc oxide/Fe.sub.2O.sub.3/nano-kaolin composite of the present invention may be used for bleeding wounds to accelerate hemostasis rate, resist bacterial infection of wounds, and promote wound healing.

[0065] A chemical formula of a term kaolin in the present specification is Al.sub.2SiO.sub.2.2H.sub.20. In some forms, kaolin contains about 45.31% of silica, about 37.21% of alumina, and about 14.1% of water.

[0066] The nano-kaolin in the embodiments in the present specification is a standard product of China Kaolin Clay Co., Ltd.

Embodiment 1

[0067] The present embodiment provides a preparation method of an Fe.sub.2O.sub.3/nano-kaolin composite, and the method includes the following steps.

[0068] 0.6 g of sodium hydroxide was weighed, and 150 mL of water was added to prepare a 0.1 mol/L sodium hydroxide solution. 2.7 g of FeCl.sub.3.6H.sub.20 was weighed, and 100 mL of deionized water was added to prepare a 0.1 mol/L FeCl.sub.3 solution. 150 mL of a 0.1 mol/L NaOH solution was slowly added dropwise to 100 mL of the 0.1 mol/L FeCl.sub.3 solution in a water bath of 70 C. under vigorous stirring. After dropwise addition, the mixed liquid was taken out to cool down slowly to obtain a stable reddish-brown transparent iron polymer solution for use. The polymer solution was labeled as a polymeric hydroxy iron ion solution.

[0069] 1 g of nano-kaolin was weighed and added to 50 mL of the 0.1 mol/L polymeric hydroxy iron ion solution. The pH of a reaction system was adjusted with a 5 mol/L NaOH solution to 3. The reaction system was heated in the water bath to 60 C. and subjected to magnetic stirring for 5 h. A product was washed, separated and dried at 60 C. The product was calcined in an air atmosphere at 250 C. for 1 h, 350 C. for 1 h, and 550 C. for 4 h respectively. A composite carrier coated with Fe.sub.2O.sub.3 on the surface of kaolin was obtained and labeled as Kaolin@Fe.sub.2O.sub.3 (iron oxide-coated nano-kaolin composite), and a granularity was 200-1000 nm.

Embodiment 2

[0070] 0.5 g of Kaolin@Fe.sub.2O.sub.3 (prepared in Embodiment 1) was weighed, 130 mL of deionized water was added, and the mixed liquid was thoroughly stirred and subjected to ultrasonic dispersion to prepare a suspension. 50 mL of a 0.01 mol/L Zn(Ac).sub.2.2H.sub.2O solution was dropwise added under vigorous stirring, so concentration of Zn.sup.2+ in a precipitation starting solution was 0.003 mol/L. After the temperature of a reaction system was increased to 40 C., 20 mL of a 5 wt % aqueous ammonia solution was dropwise added (the pH was maintained at 10-11 in a precipitation process), and the reaction lasted for 1 h. After reaction, a product was centrifugally separated and washed with deionized water for three times. After being dried at 60 C., the product was calcined at 250 C. (in an air atmosphere) for 2 h to prepare the material with nano zinc oxide supported on a Kaolin@Fe.sub.2O.sub.3 carrier, the material was labeled as ZnO/Kaolin@Fe.sub.2O.sub.3-1, the granularity of the material was 200-1000 nm, and the particle size of the surface supported zinc oxide was about 40 nm.

[0071] The prepared ZnO/Kaolin@Fe.sub.2O.sub.3-1 was sealed and stored in a drying vessel in which allochroic silicagel was placed at the bottom for use.

Embodiment 3

[0072] Compared with Embodiment 2, the main difference is that the concentration of Zn.sup.2+ in the precipitation starting solution was increased to 0.008 mol/L, and the specific operations are as follows:

[0073] 0.5 g of Kaolin@Fe.sub.2O.sub.3 (prepared in Embodiment 1) was weighed, 130 mL of deionized water was added, and the mixed liquid was thoroughly stirred and subjected to ultrasonic dispersion to prepare a suspension. 50 mL of a 0.03 mol/L Zn(Ac)2.2H20 solution was dropwise added under vigorous stirring. After the temperature of the reaction system was increased to 40 C., 20 mL of a 5 wt % aqueous ammonia solution was dropwise added, and the reaction lasted for 1 h. After reaction, a product was centrifugally separated and washed with deionized water for three times. After being dried at 60 C., the product was calcined at 250 C. for 2 h to prepare a Kaolin@Fe.sub.2O.sub.3 material with nano zinc oxide supported on the surface, the Kaolin@Fe.sub.2O.sub.3 material was labeled as ZnO/Kaolin@Fe.sub.2O.sub.3-2, the granularity of the material was 200-1000 nm, and the particle size of the surface supported zinc oxide was about 70 nm.

Embodiment 4

[0074] Compared with Embodiment 2, the main difference is that the concentration of zinc ions of a zinc source added to the reaction system was increased, the concentration of Zn.sup.2+ in the added zinc source solution was 0.014 mol/L, and the specific operations are as follows:

[0075] 0.5 g of Kaolin@Fe.sub.2O.sub.3 (prepared in Embodiment 1) was weighed, 130 mL of deionized water was added, and the mixed liquid was thoroughly stirred and subjected to ultrasonic dispersion to prepare a suspension. 50 mL of a 0.05 mol/L Zn(Ac)2.2H20 solution was dropwise added under vigorous stirring. After the temperature of the reaction system was increased to 40 C., 20 mL of a 5 wt % aqueous ammonia solution was dropwise added, and the reaction lasted for 1 h. After reaction, the product was centrifugally separated and washed with deionized water for three times. After being dried at 60 C., a product was calcined at 250 C. for 2 h and sealed and stored in a drying vessel in which allochroic silicagel was placed at the bottom for use. The material was labeled as ZnO/Kaolin@Fe.sub.2O.sub.3-3, the granularity of the material was 200-1000 nm, and the particle size of the surface supported zinc oxide was about 100 nm. The SEM graph of the material is shown in FIG. 1. The TEM graph of the material is shown in FIG. 2. FIG. 1 and FIG. 2 show the morphological patterns of zinc oxide-iron oxide-kaolin-3. Iron oxide with small particles is coated on kaolin. The larger particles are zinc oxide dispersed and supported on iron oxide-kaolin.

Embodiment 5

[0076] The present embodiment provides preparation of a zinc oxide/Fe.sub.2O.sub.3/nano kaolin-polycaprolactone/gelatin electrostatic spinning membrane (hemostatic healing-promoting fiber membrane), and the method includes the following steps.

[0077] 1 g of gelatin (type A, 300 bloom, prepared by an acid method) was weighed, 15 mL of trifluoroethanol was added, the mixed liquid was stirred and dissolved, 1 g of polycaprolactone (Mn=80000, Sigma-Aldrich) was added, and the mixed liquid was stirred at room temperature for 12 h. An acetic acid solution containing 0.2 v/v % trifluoroethanol was dropwise added. After uniform stirring, 0.13 g of a ZnO/Kaolin@Fe.sub.2O.sub.3-3 composite was added, and the mixed liquid was stirred continuously for 12 h to uniformly disperse the composite. The mixed liquid was charged into a 5 mL syringe, and a membrane was prepared by using an electrostatic spinning device, where the voltage of the tip and the collector was 20.0 kV, the distance was 15 cm, and the pushing speed was 0.003 mm/s. Gauze was fixed on a cylindrical receiver for collection, and a total of 15 mL of the mixed liquid was added for performing electrostatic spinning. After drying was performed at room temperature for 0.5 h, a fiber membrane with ZnO/Kaolin@Fe.sub.2O.sub.3-3 composited on the surface was obtained and labeled as ZnO/Kaolin@Fe.sub.2O.sub.3-3/PG. The physical image of the material is shown in FIG. 3, and the SEM graph is shown in FIG. 4.

Comparative Example 1

[0078] Compared with Embodiment 1, the difference is that no oxide (iron oxide and zinc oxide) was added, and the conditions of calcination in Embodiment 1 were used for treatment, specifically as follows:

[0079] 3 g of nano-kaolin was weighed and calcined in an air atmosphere at 250 C. for 1 h, 350 C. for 1 h, and 550 C. for 4 h respectively. The product was sealed and stored in a drying vessel in which allochroic silicagel was placed at the bottom for use. The product was labeled as Kaolin.sub.H.

Comparative Example 2

[0080] Compared with Embodiment 5, the difference is that the nano-oxide/kaolin composite hemostatic antibacterial material (ZnO/Kaolin@Fe.sub.2O.sub.3-3) of the present invention was not added, specifically as follows:

[0081] 1 g of gelatin (type A, 300 bloom, prepared by an acid method) was weighed, 15 mL of trifluoroethanol was added, the mixed liquid was stirred and dissolved, 1 g of polycaprolactone

[0082] (Mn=80000, Sigma-Aldrich) was added, and the mixed liquid was stirred at room temperature for 12 h. An acetic acid solution containing 0.2 v/v % trifluoroethanol was dropwise added. After uniform stirring, the mixed liquid was stirred continuously for 12 h. The mixed liquid was charged into a 5 mL syringe, and a membrane was prepared using an electrostatic spinning device, where the voltage of the tip and the collector was 20.0 kV, the distance was 15 cm, and the pushing speed was 0.003 mm/s. Gauze was fixed on a cylindrical receiver for collection, and a total of 15 mL of the mixed liquid was added for performing electrostatic spinning. After drying was performed at room temperature for 0.5 h, the product was sealed and stored in a drying vessel in which allochroic silicagel was placed at the bottom for use. The product was labeled as PG.

Application Embodiment

[0083] Antibacterial Experiment

[0084] A colony counting method was used, Escherichia coli (ATCC8739, Guangdong Institute of Microbiology) was used as an object, the bacterial concentration was 110.sup.5.Math.6 CFU mL.sup.1, the concentration of antibacterial powder was 0.001 g/mL, and co-culture was performed for 3 h. The antibacterial results of the cases are shown in Table 1.

TABLE-US-00001 TABLE 1 Case Material Bacterial survival rate (%) Comparative Kaolin.sub.H 113 4.7 example 1 Embodiment 1 Kaolin@Fe.sub.2O.sub.3 21.8 4 Embodiment 2 ZnO/Kaolin@Fe.sub.2O.sub.3-1 9.4 2.5 Embodiment 3 ZnO/Kaolin@Fe.sub.2O.sub.3-2 4.2 0.9 Embodiment 4 ZnO/Kaolin@Fe.sub.2O.sub.3-3 0.4 0.1 Comparative PG No obvious antibacterial example 2 property

[0085] The bacterial survival rates of Kaolin.sub.H, Kaolin@Fe.sub.2O.sub.3, ZnO/Kaolin@Fe.sub.2O.sub.3-1, ZnO/Kaolin@Fe.sub.2O.sub.3-2 and ZnO/Kaolin@Fe.sub.2O.sub.3-3 are 1134.7%, 21.84%, 9.42.5%, 4.20.9% and 0.40.1% respectively. Under the conditions, the ZnO/Kaolin@Fe.sub.2O.sub.3-3 has the lowest bacterial survival rate, the bacteria are basically inhibited, and the composite has the best bacteriostatic effect.

[0086] Hemostasis Experiment

[0087] Male BALB/C mice weighing 18.0-22.0 g were randomly grouped by body weight. The mice were immobilized, the tails were revealed, and a 1 cm wound was cut with a surgical blade at the tail ends of the mice to bleed the mice. After the incision, the corresponding material powder (shown in Table 2) was immediately given, and the bleeding time was recorded with a timer. The hemostasis time of each case is shown in Table 2.

TABLE-US-00002 TABLE 2 Case Material Bleeding time (s) Blank control group No material 223 66 Comparative example 1 Kaolin.sub.H 163 33 Embodiment 1 Kaolin@Fe.sub.2O.sub.3 178 57 Embodiment 4 ZnO/Kaolin@Fe.sub.2O.sub.3-3 129 9 Comparative example 2 PG 203 93

[0088] From Table 2, the Kaolin@Fe.sub.2O.sub.3 supported with the nano zinc oxide on the surface may effectively improve the hemostasis rate.

[0089] Healing Experiment

[0090] Male BALB/C mice weighing 18.0-22.0 g were randomly grouped by body weight. Each group of mice was anesthetized by intraperitoneal injection of chloral hydrate (10%). A circular wound of 2 cm in diameter was cut on the back skin of the mice with a pair of scissors, and then 100 uL of Escherichia coli (110.sup.5.Math.6 CFU mL.sup.1) was dropwise added. After 30 min, self-made adhesive bandages containing the material powder of Table 3 or the fiber membrane of Embodiment 5 was applied. The drug was administered every other day for 14 days. The wound area of each group of mice was measured respectively on the 3rd, 7th and 14th days after administration, and the bacterial concentration of the wound was detected. ZnO/Kaolin@Fe.sub.2O.sub.3-3/PG significantly increased the healing area of the mouse wounds on the third day of administration. ZnO/Kaolin@Fe.sub.2O.sub.3-3 and ZnO/Kaolin@Fe.sub.2O.sub.3-3/PG significantly reduced the quantity of bacteria in the mice wounds on the 7th and 14th day after administration. ZnO/Kaolin@Fe.sub.2O.sub.3-3 effectively inhibited the proliferation of wound bacteria and promoted wounds healing in a powder form or after being spun with polycaprolactone/gelatin (PG). The healing data is shown in Table 3.

TABLE-US-00003 TABLE 3 Percentage of healing area Case Material after 14 days (%) Blank control group Medical gauze 81.54 4.94 Comparative example 1 Kaolin.sub.H 88.45 1.92 Embodiment 1 Kaolin@Fe.sub.2O.sub.3 85.53 1.9 Embodiment 4 ZnO/Kaolin@Fe.sub.2O.sub.3-3 88.49 6.94 Embodiment 5 ZnO/Kaolin@Fe.sub.2O.sub.3-3/PG 91.19 2.25 Comparative example 1 PG 88.31 0.98

[0091] As shown in Table 3, if the hemostatic antibacterial material of the present invention is composited on a carrier (e.g., a fiber membrane), wound healing may be promoted.

[0092] The above description is only preferred embodiments of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements and the like made within the spirit of the present invention are included within the scope of the invention.