Preparation method of medical antibacterial gauzeTechnical Field
The invention relates to the technical field of medical gauze, in particular to a preparation method of medical antibacterial gauze.
Background
Medical gauze is a consumable used in hospitals in a large quantity, is mainly used for wound dressing, prevents microorganisms from entering wound tissues, facilitates the protection of wounds and promotes the rapid healing of the wounds. The gauze usually uses a disinfection base cloth woven by cotton fibers, has the advantages of low price, convenient use and the like, but has no antibacterial and hemostatic performances, and is easy to breed bacteria at wounds to cause wound infection to cause secondary injury. Therefore, it is necessary to develop an antibacterial gauze having good antibacterial and hemostatic functions.
The antibacterial technology based on the nano material has the advantages of simple synthesis, low cost and customization according to requirements, wherein the graphene material is a novel antibacterial agent due to the relatively low cost and the relatively low toxicity to people and environment. Compared with antibiotics, the graphene not only has broad spectrum, but also has persistence, and the antibacterial mechanism of the graphene is completely different from that of the antibiotics. Antibiotics mainly diffuse into bacteria based on drug molecules, destroy or inhibit the synthesis of specific targets of the bacteria, but the antibiotics are easy to generate drug-resistant strains and have poor sterilization effect on large-area wounds; the antibacterial activity of the graphene material mainly comprises physical puncture or a cutting mechanism called nano knife, bacterium/membrane substance damage caused by oxidative stress, transmembrane transport retardation and/or bacterium growth repression caused by coating, cell membrane instability caused by inserting and damaging cell membrane substances and the like.
At present, the application of graphene materials in gauze to achieve an antibacterial effect is widely studied. For example, in the chinese patent literature, "a method for preparing graphene oxide antibacterial and antifungal medical bandage", which is disclosed in publication No. CN105497959B, the method is: the prepared antibacterial mildew-proof agent is uniformly distributed on gauze by a spraying process, and the antibacterial mildew-proof medical bandage is obtained.
However, due to the lack of affinity between the graphene derivatives and the textile, the graphene materials are difficult to be firmly loaded on the gauze by the traditional process, and the graphene oxide is easy to fall off and run off, so that the utilization rate is greatly reduced; earlier researches prove that the sharpness of the nanosheet of the ascorbic acid reduced graphene is increased compared with that of the oxidized graphene, so that the antibacterial effect can be enhanced; in addition, the gauze cannot have dual effects of antibiosis and hemostasis by using the graphene alone.
Disclosure of Invention
The method aims to overcome the defects that in the prior art, when the graphene material is used in gauze, the graphene material is difficult to be firmly loaded on the gauze by the traditional process due to the lack of affinity between the graphene and the textile, and the utilization rate of the graphene is low; and the gauze cannot have double effects of antibiosis and hemostasis by independently using the graphene, the medical antibacterial gauze is prepared by combining graphene oxide and gauze fibers, then obtaining the gauze with the graphene nanosheet layer tightly coated with the fibers through in-situ reduction, and simultaneously anchoring the graphene on the surface of the gauze by the cyclodextrin containing thrombin, so that the medical gauze with good functions of antibiosis and hemostasis is prepared.
In order to achieve the purpose, the invention adopts the following technical scheme:
a preparation method of medical antibacterial gauze comprises the following steps:
(1) modified hydroxypropyl- β -cyclodextrin: placing the gauze in finishing liquid containing hydroxypropyl-beta-cyclodextrin and citric acid for padding treatment, then carrying out steam crosslinking, and washing to obtain hydroxypropyl-beta-cyclodextrin modified gauze;
(2) modifying graphene: dipping the gauze modified by hydroxypropyl-beta-cyclodextrin into the graphene oxide dispersion liquid, adding ascorbic acid, heating for reaction, taking out, and washing with water to obtain the gauze modified by graphene;
(3) inclusion thrombin: dipping the gauze modified by the graphene into a thrombin solution for oscillation reaction; and taking out, washing with water, and drying to obtain the medical antibacterial gauze.
Firstly, modifying hydroxypropyl-beta-cyclodextrin on the surface of cotton gauze by using citric acid as a cross-linking agent in step (1); then, in the step (2), the unreacted hydroxyl on the surface of the hydroxypropyl-beta-cyclodextrin reacts with the carboxyl on the surface of the graphene oxide, the graphene oxide is connected with the hydroxypropyl-beta-cyclodextrin, and the graphene oxide is reduced by ascorbic acid to lose redundant oxygen-containing functional groups, so that the graphene oxide is further bonded with cotton gauze fibers, the graphene is fixed on the surface of cotton gauze, the sharpness of a graphene nano-sheet layer is increased through reduction, and the contact cutting effect between the graphene and bacteria is enhanced; and finally, through the step (3), the thrombin is included in the cavity of the hydroxypropyl-beta-cyclodextrin, so that the medical antibacterial gauze of the cyclodextrin inclusion compound with the graphene and the thrombin loaded on the surface is obtained.
According to the method, the graphene nanosheets are connected to the surface of the gauze through chemical reaction by utilizing the hydroxypropyl-beta-cyclodextrin, so that the graphene nanosheets are high in adhesion strength on the surface of the gauze, strong in firmness and not easy to fall off. The graphene nanosheet layer can endow the gauze with excellent antibacterial performance, so that effective bacteriostasis is realized, and wound healing is promoted; moreover, the graphene has broad-spectrum antibacterial property and long antibacterial aging, and reduces the gauze replacement frequency and the pain of a patient caused by gauze replacement. Meanwhile, the thrombin is included in the cavity of the hydroxypropyl-beta-cyclodextrin to obtain the thrombin inclusion compound, the heat stability of the thrombin is improved by utilizing the inclusion effect, the slow release of the thrombin is realized, the acting time of the thrombin is ensured, the effect of the thrombin is fully exerted, and the gauze has the hemostatic effect. Therefore, the gauze prepared by the invention has good antibacterial and hemostatic effects, is beneficial to promoting wound healing and relieving the pain of patients.
Preferably, the components of the finishing liquid in the step (1) comprise the following components in parts by weight: 2-5 parts of hydroxypropyl-beta-cyclodextrin, 7-8 parts of citric acid, 1-3 parts of sodium dihydrogen phosphate and 90-110 parts of water.
Preferably, the liquid carrying rate of the cotton gauze subjected to padding treatment in the step (1) is 100-110%; the steam crosslinking temperature is 140-180 ℃, and the steam crosslinking time is 2-5 min.
And (2) the citric acid is subjected to dehydration reaction at the crosslinking temperature to generate a plurality of cyclic acid anhydrides, wherein one part of the cyclic acid anhydrides is subjected to esterification reaction with hydroxyl on the surface of the cotton fiber under the action of a catalyst sodium dihydrogen phosphate, and the other part of the cyclic acid anhydrides is subjected to esterification reaction with hydroxyl in the hydroxypropyl-beta-cyclodextrin, so that the hydroxypropyl-beta-cyclodextrin is modified on the surface of the gauze under the bridge action of the citric acid.
Preferably, the gauze in the step (1) is absorbent cotton gauze, and the absorbent cotton gauze is washed by water and pre-dried before the dipping reaction, wherein the pre-drying temperature is 130-140 ℃, and the pre-drying time is 2-3 min.
Preferably, the concentration of the graphene oxide in the graphene oxide dispersion liquid in the step (2) is 1-3 mg/mL; the mass ratio of the added ascorbic acid to the added graphene oxide is as follows: 0.5-10: 1.
By adopting the reaction dosage of each component in the invention, the medical gauze has good antibacterial and hemostatic performances, and simultaneously does not damage the performances of the gauze such as air permeability, water retention performance, skin affinity and the like, and can quickly absorb wound exudate to keep the relative dryness of the wound and create a local environment which is beneficial to wound healing.
Preferably, the heating reaction in the step (2) is carried out at the temperature of 60-95 ℃ for 2-4 h.
Preferably, the concentration of the thrombin solution in the step (3) is 200-300 IU/mL.
Preferably, in the step (3), the oscillating reaction temperature is 2-4 ℃, and the reaction time is 8-12 h.
Preferably, the air drying temperature in the step (3) is 5-10 ℃.
Preferably, the step (3) is performed with ultrasonic oscillation at an ultrasonic power of 500-800W.
Therefore, the invention has the following beneficial effects:
(1) the hydroxypropyl-beta-cyclodextrin is utilized to connect the graphene nanosheet layer to the surface of the cotton gauze through chemical reaction, so that the graphene nanosheet layer is high in adhesion strength on the surface of cotton fiber, strong in firmness and not easy to fall off;
(2) the loaded graphene nanosheet layer reduced by the ascorbic acid can endow the gauze with stronger antibacterial performance, and the sharpness of the graphene nanosheet layer is increased by the ascorbic acid reduction operation, so that the contact cutting effect of the graphene nanosheet layer and bacteria is enhanced, and therefore high-efficiency bacteriostasis is realized, and wound healing is promoted; meanwhile, the graphene has broad-spectrum antibacterial property and long antibacterial aging, so that the gauze replacement frequency is reduced, and the pain of a patient caused by gauze replacement is reduced;
(3) thrombin is included in a cavity of hydroxypropyl-beta-cyclodextrin to obtain a thrombin inclusion compound, the stability of the thrombin is improved by utilizing the inclusion effect, the slow release of the thrombin is realized, the acting time of the thrombin is ensured, the efficacy of the thrombin is fully exerted, and the gauze has a hemostatic effect;
(4) the medical antibacterial gauze does not damage the performances of the gauze such as air permeability, water holding performance, skin affinity and the like, can quickly absorb wound exudates to keep the relative dryness of the wound, and creates a local environment which is beneficial to wound healing.
Detailed Description
The invention is further described with reference to specific embodiments.
In the present invention, all the equipment and materials are commercially available or commonly used in the art, and the methods in the following examples are conventional in the art unless otherwise specified.
Example 1:
a preparation method of medical antibacterial gauze comprises the following steps:
(1) pre-drying the degreased cotton yarn after water distribution, wherein the pre-drying temperature is 135 ℃, and the pre-drying time is 2.5 min;
(2) modified hydroxypropyl- β -cyclodextrin: placing the absorbent cotton yarn in finishing liquid for padding treatment, wherein the finishing liquid comprises the following components in parts by weight: 3 parts of hydroxypropyl-beta-cyclodextrin, 7.5 parts of citric acid, 2 parts of sodium dihydrogen phosphate and 100 parts of water; the liquid carrying rate of the gauze after padding treatment is 102 percent; then carrying out steam crosslinking at the crosslinking temperature of 150 ℃ for 3min, and washing to obtain hydroxypropyl-beta-cyclodextrin modified gauze;
(3) modifying graphene: dipping the gauze modified by hydroxypropyl-beta-cyclodextrin into graphene oxide dispersion liquid with the concentration of 2mg/mL, adding ascorbic acid with the mass ratio of 0.5:1 to the graphene oxide, heating and reacting for 3h at 80 ℃, taking out and washing with water to obtain the gauze modified by graphene;
(4) inclusion thrombin: soaking the graphene-modified gauze in a thrombin solution with the concentration of 250IU/mL, and carrying out ultrasonic oscillation reaction at 2 ℃ for 10 hours with the ultrasonic power of 600W; taking out, washing with water, and drying with 8 ℃ cold air to obtain the medical antibacterial gauze.
Example 2:
a preparation method of medical antibacterial gauze comprises the following steps:
(1) pre-drying the degreased cotton yarn after water distribution, wherein the pre-drying temperature is 130 ℃, and the pre-drying time is 3 min;
(2) modified hydroxypropyl- β -cyclodextrin: placing the absorbent cotton yarn in finishing liquid for padding treatment, wherein the finishing liquid comprises the following components in parts by weight: 2 parts of hydroxypropyl-beta-cyclodextrin, 7 parts of citric acid, 1 part of sodium dihydrogen phosphate and 90 parts of water; the liquid carrying rate of the gauze after padding treatment is 110%; then carrying out steam crosslinking at the crosslinking temperature of 140 ℃ for 5min, and washing to obtain hydroxypropyl-beta-cyclodextrin modified gauze;
(3) modifying graphene: dipping the gauze modified by hydroxypropyl-beta-cyclodextrin into graphene oxide dispersion liquid with the concentration of 1mg/mL, adding ascorbic acid with the mass ratio of 5:1 to the graphene oxide, heating and reacting for 4h at 60 ℃, taking out and washing with water to obtain the gauze modified by graphene;
(4) inclusion thrombin: soaking the graphene-modified gauze in a thrombin solution with the concentration of 200IU/mL, and carrying out ultrasonic oscillation reaction at 2 ℃ for 12 hours with the ultrasonic power of 500W; taking out, washing with water, and drying with cold air at 5 ℃ to obtain the medical antibacterial gauze.
Example 3:
a preparation method of medical antibacterial gauze comprises the following steps:
(1) pre-drying the degreased cotton yarn after water distribution, wherein the pre-drying temperature is 140 ℃, and the pre-drying time is 2 min;
(2) modified hydroxypropyl- β -cyclodextrin: placing the absorbent cotton yarn in finishing liquid for padding treatment, wherein the finishing liquid comprises the following components in parts by weight: 5 parts of hydroxypropyl-beta-cyclodextrin, 8 parts of citric acid, 3 parts of sodium dihydrogen phosphate and 110 parts of water; the liquid carrying rate of the gauze after padding treatment is 100 percent; then carrying out steam crosslinking at 180 ℃ for 2min, and washing to obtain hydroxypropyl-beta-cyclodextrin modified gauze;
(3) modifying graphene: dipping the gauze modified by hydroxypropyl-beta-cyclodextrin into graphene oxide dispersion liquid with the concentration of 3mg/mL, adding ascorbic acid with the mass ratio of the ascorbic acid to the graphene oxide of 10:1, heating and reacting for 3h at 95 ℃, taking out, and washing with water to obtain the gauze modified by graphene;
(4) inclusion thrombin: soaking the graphene-modified gauze in a thrombin solution with the concentration of 300IU/mL, and carrying out ultrasonic oscillation reaction at 4 ℃ for 8 hours with the ultrasonic power of 800W; taking out, washing with water, and drying with cold air at 10 ℃ to obtain the medical antibacterial gauze.
Comparative example 1 (unmodified hydroxypropyl- β -cyclodextrin):
a preparation method of medical antibacterial gauze comprises the following steps:
(1) pre-drying the degreased cotton yarn after water distribution, wherein the pre-drying temperature is 135 ℃, and the pre-drying time is 2.5 min;
(2) modifying graphene: soaking absorbent cotton gauze in graphene oxide dispersion liquid with the concentration of 2mg/mL, adding ascorbic acid with the mass ratio of 0.5:1 to the graphene oxide, heating to react for 3 hours at 80 ℃, taking out and washing with water to obtain graphene-modified gauze;
(3) inclusion thrombin: soaking the graphene-modified gauze in a thrombin solution with the concentration of 250IU/mL, and carrying out ultrasonic oscillation reaction at 2 ℃ for 10 hours with the ultrasonic power of 600W; taking out, washing with water, and drying with 8 ℃ cold air to obtain the medical antibacterial gauze.
Comparative example 2 (without graphene modification):
a preparation method of medical antibacterial gauze comprises the following steps:
(1) pre-drying the degreased cotton yarn after water distribution, wherein the pre-drying temperature is 135 ℃, and the pre-drying time is 2.5 min;
(2) modified hydroxypropyl- β -cyclodextrin: placing the absorbent cotton yarn in finishing liquid for padding treatment, wherein the finishing liquid comprises the following components in parts by weight: 3 parts of hydroxypropyl-beta-cyclodextrin, 7.5 parts of citric acid, 2 parts of sodium dihydrogen phosphate and 100 parts of water; the liquid carrying rate of the gauze after padding treatment is 102 percent; then carrying out steam crosslinking at the crosslinking temperature of 150 ℃ for 3min, and washing to obtain hydroxypropyl-beta-cyclodextrin modified gauze;
(3) inclusion thrombin: immersing the gauze modified by hydroxypropyl-beta-cyclodextrin into thrombin solution with the concentration of 250IU/mL, and carrying out ultrasonic oscillation reaction for 10 hours at the temperature of 2 ℃ with the ultrasonic power of 600W; taking out, washing with water, and drying with 8 ℃ cold air to obtain the medical antibacterial gauze.
Comparative example 3 (no thrombin inclusion):
a preparation method of medical antibacterial gauze comprises the following steps:
(1) pre-drying the degreased cotton yarn after water distribution, wherein the pre-drying temperature is 135 ℃, and the pre-drying time is 2.5 min;
(2) modified hydroxypropyl- β -cyclodextrin: placing the absorbent cotton yarn in finishing liquid for padding treatment, wherein the finishing liquid comprises the following components in parts by weight: 3 parts of hydroxypropyl-beta-cyclodextrin, 7.5 parts of citric acid, 2 parts of sodium dihydrogen phosphate and 100 parts of water; the liquid carrying rate of the gauze after padding treatment is 102 percent; then carrying out steam crosslinking at the crosslinking temperature of 150 ℃ for 3min, and washing to obtain hydroxypropyl-beta-cyclodextrin modified gauze;
(3) modifying graphene: immersing gauze modified by hydroxypropyl-beta-cyclodextrin into graphene oxide dispersion liquid with the concentration of 2mg/mL, adding ascorbic acid with the mass ratio of 0.5:1 to the graphene oxide, heating and reacting for 3h at 80 ℃, taking out, and washing with water to obtain the medical antibacterial gauze.
The antibacterial property and hemostatic property of the medical antibacterial gauze prepared in the above examples and comparative examples were measured after washing 20 times, and the results are shown in table 1.
The antibacterial property test method refers to an absorption method in GB/T20944.2-2007 evaluation of antibacterial property of textiles.
The testing method of the hemostatic performance comprises the following steps: the medical antibacterial gauze prepared in the above examples and comparative examples was cut into 1cm × 1cm as a sample of an experimental group, the absorbent cotton gauze without modification treatment was cut into 1cm × 1cm as a sample of a blank control group, each sample was placed in a 15mL centrifuge tube, preheated in a 37 ℃ water bath for 5min, and then 0.2mL fresh rabbit blood and 20. mu.L 0.2mol/L CaCl were added to the tube2The solutions were incubated in a shaker for 5min each. The free hemoglobin amount is marked by an enzyme labeling instrument to obtain an absorbance value A of an experimental group and an absorbance value A of a blank control group0Calculating blood coagulation index BCI: BCI ═ A/A0X is 100%; the lower the BCI, the better the hemostatic effect.
Table 1: and (5) testing the antibacterial and hemostatic performance of the gauze.
As can be seen from table 1, the medical antibacterial gauze prepared by the method of the present invention in examples 1 to 3 has good antibacterial performance and hemostatic effect after being washed 20 times with water. In the comparative example 1, the hydroxypropyl-beta-cyclodextrin layer is not modified on the surface of the gauze, so that the antibacterial property and the hemostatic effect are remarkably reduced after 20 times of washing, probably because the graphene cannot be firmly connected with the gauze, the thrombin cannot be effectively loaded on the surface of the gauze through inclusion, and the loss of the graphene and the thrombin after washing is more. In the comparative example 2, the surface of the gauze is not loaded with graphene, so that the antibacterial property of the gauze is poor, the action between the graphene and thrombin is lacked, the fixing action of the thrombin is weakened, and the hemostatic effect is poor; in comparative example 3, thrombin is not encapsulated in hydroxypropyl-beta-cyclodextrin, and the hemostatic effect of the gauze is poor, so that the use requirements of medical gauze are not met. The medical gauze with good antibacterial and hemostatic functions can be prepared by anchoring the graphene on the surface of the gauze through the cyclodextrin included with the thrombin.