Bacteria-responsive hemostatic antibacterial cotton fabric and preparation method thereof

Abstract

The invention relates to a bacteria-responsive hemostatic antibacterial cotton fabric and a preparation method thereof. The oxidized cotton fabric and the cationic hemostatic antibacterial agent rich in amino are connected together by utilizing amino-modified phosphate, so that the hemostatic antibacterial functional finishing of the cotton fabric is realized. Compared with common nano-silver, the selected antibacterial agent has better biological safety. The obtained cotton fabric can be applied to the fields of medical treatment and clothing, and has biological responsiveness: the cotton fabric has inherent antibacterial and hemostatic capabilities in a common use environment, and chemical grafting ensures sufficient washability; and when the body is colonized by a large amount of bacteria, the bacterial responsive phosphate bond is catalyzed by the alkaline phosphatase secreted by the bacteria to break, and the free antibacterial agent is released and enters the tissue to kill the bacteria, so that the rapid recovery of infectious diseases is promoted.

Description

Technical Field

[0001] The invention relates to the field of functional finishing of cotton fabrics, and in particular to a bacteria-responsive hemostatic and antibacterial cotton fabric and a preparation method thereof. Background Art

[0002] Cotton fabric is a kind of natural textile material with wide application, especially in the clothing and medical industries. However, with the increasing multifunctionality of social development, the biologically inert traditional cotton textiles can no longer meet people's needs, resulting in a variety of functional finishing of cotton fabrics. Among them, since cotton products often face the invasion of pathogens such as bacteria, fungi, viruses, etc. during use, as well as bleeding problems after injury, antibacterial and hemostasis have become the two key directions of functional finishing of cotton fabrics.

[0003] The antibacterial finishing of cotton fabrics is generally achieved by introducing antibacterial agents by physical methods or groups with antibacterial efficacy by chemical methods. The antibacterial agents currently used mainly include three categories: inorganic antibacterial agents, organic antibacterial agents and natural antibacterial agents. Among them, nanosilver in inorganic antibacterial agents is the most used and has excellent bactericidal effects, but it also has two major disadvantages: biological toxicity that may be caused by a large amount of accumulation and inability to stably remain on fabrics. For antibacterial fabrics, washability is a key parameter, that is, how many times the antibacterial effect can remain stable after repeated washing, because most cotton fabric products are not disposable, and temporary antibacterial properties are not practical. In order to improve the retention rate of silver on the surface of fabrics, methods such as adhesives, microwave radiation, ultrasonic irradiation, and fiber surface modification have been developed, so that the problem of poor washability has been solved to a certain extent, but the potential biosafety problem of nanosilver still exists.

[0004] At present, the hemostatic products on the market can be divided into inorganic hemostatic powders such as zeolite and kaolin and hemostatic sponges such as chitosan and gelatin. Inorganic hemostatic powders have a large specific surface area and can react quickly with blood, but they often generate a lot of heat when stopping bleeding, causing additional tissue burns, and because they cannot be degraded, they are prone to accumulate and cause thrombosis after entering the blood vessels. Hemostatic materials with cationic properties such as chitosan can promote blood coagulation by inducing the aggregation of negatively charged red blood cells and platelets, and are degradable and will not cause side effects, but in terms of the form of action, they are still separate hemostatic materials and need to be carried additionally. Ordinary people will also suffer from excessive blood loss while waiting for hemostatic materials without preparation.

[0005] In addition, the biofunctional finishing of fabrics faces a huge challenge: the ability to recognize and respond to the physiological environment. Bioresponsive materials refer to materials that are extremely sensitive to biological signals or pathologies, such as pH, redox, enzymes, glucose, ions, hypoxia, temperature, etc., and can interact with them or be stimulated by them. Intelligent biomaterials are the stepping stone to the realization of the next generation of precision medicine. For example, for the antibacterial function of fabrics, when the human body is not traumatized and the intact skin barrier still exists, the inherent antibacterial ability is more suitable, and there is no need to release antibacterial agents into the tissue environment; when wounds appear, the skin barrier is destroyed, and the body is directly exposed to the threat of pathogens or even infected, simply relying on inherent antibacterial fabrics to contact and sterilize tissues is no longer the optimal solution. Releasing antibacterial agents deep into the tissue to assist the immune system in killing invading pathogens is the first choice for controlling infection and alleviating the condition. It can be seen that the antibacterial finishing method of cotton fabrics with bioresponsiveness can face changes in the physiological environment more flexibly and promote the rapid recovery of health through more active response strategies. Summary of the invention

[0006] In view of the above problems, the purpose of the present invention is to provide a bacterial responsive hemostatic antibacterial cotton fabric and a preparation method thereof. The fabric is obtained by grafting a cationic hemostatic antibacterial agent to a basic cotton fabric through a phosphate bond after oxidation. During normal use, the hemostatic antibacterial properties can be maintained and the washing resistance is excellent; when bacterial infection occurs, the phosphate bond can be broken under the action of alkaline phosphatase secreted by the bacteria, which is the so-called bacterial responsiveness, thereby releasing the antibacterial agent into the tissue environment, killing deep bacteria and promoting rapid healing of wounds.

[0007] To achieve the above object, the present invention provides the following technical solution, a bacteria-responsive hemostatic and antibacterial cotton fabric, and the specific preparation method is as follows:

[0008] (1) using phosphoryl chloride and amino alcohol to react to obtain amino-modified phosphate;

[0009] (2) oxidizing the base cotton fabric to obtain an oxidized cotton fabric containing a carboxyl group;

[0010] (3) coupling the amino-modified phosphate obtained in (1) with the oxidized cotton fabric obtained in (2);

[0011] (4) further coupling the cationic hemostatic antibacterial agent to the phosphate ester-cotton fabric conjugate obtained in (3);

[0012] Furthermore, the phosphorus oxychloride described in step (1) is at least one of phosphorus oxychloride, phenylphosphoryl dichloride, ethyl dichlorophosphate, pyrophosphoryl chloride, bis(2-oxo-3-oxazolidinyl)phosphinoyl chloride, and diethylphosphoryl chloride, and the amino alcohol is at least one of 2-aminocycloethanol, 4-amino-1-butanol, 3-amino-1-propanol, 5-amino-1-pentanol, 2-amino-1,3-propanediol, phenylphosphoryl dichloride and its isomers; the phosphorus oxychloride and the amino alcohol are mixed and reacted in a solvent, the solvent is at least one of dichloromethane, dimethyl sulfoxide, chloroform, acetone, and ether, the feed molar ratio is phosphorus oxychloride:amino alcohol=1:0.5-10, the feed concentration is 5-50 mg / mL, the reaction temperature is 5-40°C, the reaction pH is 6-10, the reaction time is 8-24h, the reaction is carried out under an inert gas atmosphere, and the extraction, reduced pressure distillation, and silica gel column chromatography are performed for purification.

[0013] Furthermore, the oxidation process of the basic cotton fabric described in step (2) is chemical oxidation, the oxidant used is at least one of potassium dichromate, sodium periodate, 2,2,6,6-tetramethylpiperidine-1-oxyl free radical, hydrogen peroxide, and sodium hypochlorite, the basic cotton fabric is immersed in an oxidant solution for reaction, the solvent is water, the concentrations of the cotton fabric and the oxidant are 10-100 mg / mL and 0.1-50 wt %, respectively, the oxidation temperature is 15-60° C., the oxidation pH is 1-10, the oxidation time is 8-48 h, washing, drying and purification are performed, and the carboxyl content in the obtained oxidized cotton fabric is 0.05-0.35 mmol / g.

[0014] Furthermore, the coupling of the amino-modified phosphate and the oxidized cotton fabric described in step (3) is achieved through an amidation reaction between an amino group and a carboxyl group, specifically comprising: first adding the oxidized cotton fabric to a solvent, adding a catalyst to activate the carboxyl group in the oxidized cotton fabric for 1-2 hours, then adding the amino-modified phosphate to react, washing, drying and purifying; wherein the solvent is water, the carboxyl feed concentration is 5-10 mmol / mL, the carboxyl and amino feed molar ratio is 1:0.8-1.2, the catalyst type and amount are 1-ethyl-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide, and 1-1.5 times the amount of carboxyl, the reaction temperature is 5-40°C, the reaction pH is 4-6, and the reaction time is 8-24 hours.

[0015] Furthermore, the cationic hemostatic antibacterial agent described in step (4) is at least one of chitosan containing amino groups, hyperbranched polylysine, and quaternary ammonium salts or guanidine antibacterial agents. Under the action of a cross-linking agent, the amino groups in the antibacterial agent react with the amino groups in the phosphate-cotton fabric conjugate to achieve the second step of coupling. The solvent is water, the concentration of the antibacterial agent is 1-20 mg / mL, the molar ratio of the antibacterial agent to the amino groups in the phosphate-cotton fabric conjugate is 1:0.05-1, the cross-linking agent is glutaraldehyde or genipin, and its amount is 1-1.5 times the number of amino groups in the phosphate-cotton fabric conjugate. The reaction temperature is 15-40°C, the reaction pH is 4-9, and the reaction time is 4-24h. After washing, drying, packaging and sterilization, a hemostatic antibacterial cotton fabric with bacterial responsiveness is obtained.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] 1. The present invention provides a bacteria-responsive hemostatic and antibacterial cotton fabric, in which the hemostatic and antibacterial agent is grafted onto the cotton fabric by chemical grafting. The fabric has excellent washability in a common use environment without bacterial infection, thus solving the problem of the retention of the antibacterial agent.

[0018] 2. The present invention provides a bacteria-responsive hemostatic and antibacterial cotton fabric, in which the functional finishing agent used is an amino-rich polycation, such as hyperbranched polylysine, which can simultaneously achieve hemostasis and antibacterial properties, and its cytotoxicity is much lower than that of commonly used nanosilver antibacterial agents, thereby improving biosafety.

[0019] 3. The bacterial-responsive hemostatic and antibacterial cotton fabric provided by the present invention has bacterial responsiveness and can adapt to the use environment. When the fabric comes into contact with tissue infected with bacteria, the alkaline phosphatase produced by a large number of bacterial activities can efficiently catalyze the breaking of phosphate bonds in the fabric, releasing the grafted hemostatic and antibacterial agent into the deep tissue that the inherent antibacterial fabric cannot reach, thereby quickly killing bacteria and accelerating tissue repair. DETAILED DESCRIPTION

[0020] The technical solution of the present invention is further illustrated below in conjunction with embodiments, but these embodiments are not intended to limit the present invention.

[0021] Embodiment 1:

[0022] (1) Under nitrogen protection, ethyl dichlorophosphate and 3-amino-1-propanol were dissolved in anhydrous dichloromethane at concentrations of 16.29 mg / mL and 15.02 mg / mL, respectively, and reacted at 25° C. and pH=6.8 for 12 h. The mixture was extracted, distilled under reduced pressure, and purified by silica gel column chromatography.

[0023] (2) The base cotton fabric was immersed in a 50 wt % hydrogen peroxide aqueous solution at a concentration of 50 mg / mL, oxidized at 25° C. and pH=4.5 for 8 h, and then washed, dried and purified.

[0024] (3) The oxidized cotton fabric was immersed in a mixed aqueous solution of 10 mg / mL 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 8 mg / mL N-hydroxysuccinimide at a concentration of 50 mg / mL, activated at 25 degrees Celsius and pH = 4.5 for 1 hour, and then 11.58 mg / mL of the amino-modified phosphate prepared in (1) was added, the reaction was continued for 12 hours, and then washed, dried and purified.

[0025] (4) The phosphate-cotton fabric conjugate and hyperbranched polylysine prepared in (3) were dissolved in water at 50 mg / mL and 5 mg / mL, respectively, and 1 mg / mL of genipin was added. The mixture was reacted at 25 degrees Celsius and pH = 5 for 12 hours. After washing, drying, packaging and sterilization, a hemostatic and antibacterial cotton fabric with bacterial responsiveness was obtained.

[0026] Embodiment 2:

[0027] (1) Under nitrogen protection, ethyl dichlorophosphate and 3-amino-1-propanol were dissolved in anhydrous dichloromethane at concentrations of 16.29 mg / mL and 15.02 mg / mL, respectively, and reacted at 25° C. and pH=6.8 for 12 h. The mixture was extracted, distilled under reduced pressure, and purified by silica gel column chromatography.

[0028] (2) The base cotton fabric was immersed in a mixed aqueous solution of 0.016 mg / mL 2,2,6,6-tetramethylpiperidin-1-oxyl free radical, 0.08 mg / mL sodium hypochlorite and 0.1 mg / mL sodium bromide at a concentration of 20 mg / mL, oxidized at 25°C and pH = 10 for 8 h, washed, dried and purified.

[0029] (3) The oxidized cotton fabric was immersed in a mixed aqueous solution of 10 mg / mL 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 8 mg / mL N-hydroxysuccinimide at a concentration of 50 mg / mL, activated at 25 degrees Celsius and pH = 4.5 for 1 hour, and then 11.58 mg / mL of the amino-modified phosphate obtained in (1) was added, the reaction was continued for 12 hours, and then washed, dried and purified.

[0030] (4) The phosphate-cotton fabric conjugate and hyperbranched polylysine obtained in (3) were dissolved in water at 50 mg / mL and 5 mg / mL, respectively, and 1 mg / mL of genipin was added. The mixture was reacted at 25 degrees Celsius and pH = 5 for 12 hours. After washing, drying, packaging and sterilization, a hemostatic and antibacterial cotton fabric with bacterial responsiveness was obtained.

[0031] Embodiment 3:

[0032] (1) Under nitrogen protection, ethyl dichlorophosphate and 3-amino-1-propanol were dissolved in anhydrous dichloromethane at concentrations of 16.29 mg / mL and 15.02 mg / mL, respectively, and reacted at 25° C. and pH=6.8 for 12 h. The mixture was extracted, distilled under reduced pressure, and purified by silica gel column chromatography.

[0033] (2) The base cotton fabric was immersed in a 50 wt % hydrogen peroxide aqueous solution at a concentration of 50 mg / mL, oxidized at 25° C. and pH=4.5 for 8 h, and then washed, dried and purified.

[0034] (3) The oxidized cotton fabric was immersed in a mixed aqueous solution of 10 mg / mL 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 8 mg / mL N-hydroxysuccinimide at a concentration of 50 mg / mL, activated at 25 degrees Celsius and pH = 4.5 for 1 hour, and then 11.58 mg / mL of the amino-modified phosphate obtained in (1) was added, the reaction was continued for 12 hours, and then washed, dried and purified.

[0035] (4) The phosphate-cotton fabric conjugate and quaternary ammonium salt chitosan obtained in (3) were dissolved in water at 50 mg / mL and 5 mg / mL, respectively, and 2 mg / mL of glutaraldehyde was added. The mixture was reacted at 25 degrees Celsius and pH = 8.5 for 12 hours. After washing, drying, packaging and sterilization, a hemostatic and antibacterial cotton fabric with bacterial responsiveness was obtained.

[0036] The above are only some preferred embodiments of the present invention and are not intended to limit the present invention. Those skilled in the art should understand that any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for preparing a bacteria-responsive hemostatic and antibacterial cotton fabric, characterized in that: These include: (1) using phosphoryl chloride and amino alcohol to react to obtain amino-modified phosphate; (2) oxidizing the base cotton fabric to obtain an oxidized cotton fabric containing a carboxyl group; (3) coupling the amino-modified phosphate obtained in (1) with the oxidized cotton fabric obtained in (2); (4) The cationic hemostatic antibacterial agent is further coupled to the phosphate-cotton fabric conjugate obtained in (3) to obtain a bacteria-responsive hemostatic antibacterial cotton fabric.

2. The method for preparing a bacteria-responsive hemostatic and antibacterial cotton fabric according to claim 1, characterized in that: The phosphorus oxychloride described in step (1) is at least one of phosphorus oxychloride, phenylphosphoryl dichloride, ethyl dichlorophosphate, pyrophosphoryl chloride, bis(2-oxo-3-oxazolidinyl)phosphinoyl chloride, and diethylphosphoryl chloride, and the amino alcohol is at least one of 2-aminocycloethanol, 4-amino-1-butanol, 3-amino-1-propanol, 5-amino-1-pentanol, 2-amino-1,3-propanediol, phenylphosphoryl dichloride and its isomers.

3. The method for preparing a bacteria-responsive hemostatic and antibacterial cotton fabric according to claim 1, characterized in that: In step (1), phosphorus oxychloride and amino alcohol are mixed and reacted in a solvent, wherein the solvent is at least one of dichloromethane, dimethyl sulfoxide, chloroform, acetone and diethyl ether, the feed molar ratio is phosphorus oxychloride:amino alcohol=1:0.5-10, the feed concentration is 5-50 mg / mL, the reaction temperature is 5-40°C, the reaction pH is 6-10, the reaction time is 8-24h, the reaction is carried out under an inert gas atmosphere, and the extraction, reduced pressure distillation and silica gel column chromatography are performed for purification.

4. The method for preparing a bacteria-responsive hemostatic and antibacterial cotton fabric according to claim 1, characterized in that: The oxidation process of the basic cotton fabric described in step (2) is chemical oxidation, and the oxidant used is at least one of potassium dichromate, sodium periodate, 2,2,6,6-tetramethylpiperidine-1-oxyl free radical, sodium hypochlorite, and hydrogen peroxide. The basic cotton fabric is immersed in an oxidant solution for reaction, the solvent is water, the concentrations of the cotton fabric and the oxidant are 10-100 mg / mL and 0.1-50 wt % respectively, the oxidation temperature is 15-60° C., the oxidation pH is 1-10, the oxidation time is 8-48 h, and the fabric is washed, dried, and purified. The carboxyl content in the obtained oxidized cotton fabric is 0.05-0.35 mmol / g.

5. The method for preparing a bacteria-responsive hemostatic and antibacterial cotton fabric according to claim 1, characterized in that: The coupling of the amino-modified phosphate and the oxidized cotton fabric described in step (3) is achieved through an amidation reaction between an amino group and a carboxyl group, which specifically comprises: firstly adding the oxidized cotton fabric into a solvent, adding a catalyst to activate the carboxyl group in the oxidized cotton fabric for 1-2 hours, then adding the amino-modified phosphate to react, washing, drying and purifying; wherein the solvent is water, the carboxyl feed concentration is 5-10 mmol / mL, the carboxyl and amino feed molar ratio is 1:0.8-1.2, the catalyst types are 1-ethyl-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide, the amount used is 1-1.5 times the molar amount of the carboxyl group, the reaction temperature is 5-40°C, the reaction pH is 4-6, and the reaction time is 8-24 hours.

6. The method for preparing a bacteria-responsive hemostatic and antibacterial cotton fabric according to claim 1, characterized in that: The cationic hemostatic antibacterial agent described in step (4) is at least one of chitosan, hyperbranched polylysine, quaternary ammonium salts or guanidine antibacterial agents containing amino groups. Under the action of a cross-linking agent, the amino groups in the antibacterial agent react with the amino groups in the phosphate-cotton fabric conjugate to achieve the second step of coupling. The solvent is water, the concentration of the antibacterial agent is 1-20 mg / mL, the molar ratio of the antibacterial agent to the amino groups in the phosphate-cotton fabric conjugate is 1:0.05-1, the cross-linking agent is genipin or glutaraldehyde, and the amount thereof is 1-1.5 times the number of amino groups in the phosphate-cotton fabric conjugate. The reaction temperature is 15-40°C, the reaction pH is 4-9, and the reaction time is 4-24h. After washing, drying, packaging and sterilization, a hemostatic antibacterial cotton fabric with bacterial responsiveness is obtained.

7. A bacteria-responsive hemostatic and antibacterial cotton fabric, characterized in that: The method is prepared by the method according to any one of claims 1 to 6.

8. The use of cotton fabric according to claim 7, characterized in that: Used in the preparation of medical supplies for wound hemostasis and / or infection protection.