Bacteria-responsive hemostatic and antibacterial cotton fabric and preparation method thereof

Abstract

The present invention relates to a bacteria-responsive hemostatic and antibacterial cotton fabric and a preparation method thereof. By utilizing amino-modified phosphate ester, the oxidized cotton fabric and the amino-rich cationic hemostatic and antibacterial agent are connected together, thereby realizing the hemostatic and antibacterial functional finishing of the cotton fabric. The selected antibacterial agent has better biosafety than the commonly used nanosilver. The obtained cotton fabric can be applied to the medical and clothing fields and has bioresponsiveness: it has inherent antibacterial and hemostatic ability under normal use environment, and chemical grafting ensures sufficient wash resistance; and when the body is colonized by a large number of bacteria, the bacteria-responsive phosphate bond is catalyzed by the alkaline phosphatase secreted by the bacteria to break, releasing the free antibacterial agent, which enters the tissue to kill bacteria, thereby promoting rapid recovery from infectious diseases.

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 natural textile material with a wide range of applications, especially in the clothing and medical industries. However, with the increasing multifunctionality of social development, traditional biologically inert cotton textiles can no longer meet people's needs. As a result, a variety of functional finishing methods for cotton fabrics have emerged. Among them, since cotton products often face the invasion of pathogens such as bacteria, fungi, and viruses during use, as well as bleeding problems after damage, 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 antimicrobial agents through physical methods or groups with antimicrobial efficacy through chemical methods. Currently used antimicrobial agents mainly include three categories: inorganic antimicrobial agents, organic antimicrobial agents, and natural antimicrobial agents. Among them, nanosilver is the most widely used inorganic antimicrobial agent and has excellent bactericidal effect, but it also has two major disadvantages: biotoxicity that may result from large-scale accumulation and inability to stably remain on the fabric. For antimicrobial fabrics, washability is a key parameter, that is, how many times the antimicrobial effect can remain stable after repeated washing. Because most cotton fabric products are not disposable, temporary antimicrobial properties are not practical. In order to improve the retention rate of silver on the fabric surface, methods such as adhesives, microwave radiation, ultrasonic irradiation, and fiber surface modification have all been developed. The problem of poor washability has been solved to a certain extent, but the potential biosafety issue of nanosilver still exists.

[0004] Currently, commercially available hemostatic products 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 large amount of heat during hemostasis, causing additional tissue burns. Moreover, since they are non-degradable, they can easily accumulate in blood vessels and cause thrombosis. Cationic hemostatic materials such as chitosan can promote coagulation by inducing the aggregation of negatively charged red blood cells and platelets. They are also biodegradable and have no side effects. However, they still function as separate hemostatic materials that need to be carried separately. Unprepared individuals can suffer from excessive bleeding while waiting for hemostatic materials.

[0005] Furthermore, biofunctionalized fabric finishing faces a significant challenge: the ability to recognize and respond to physiological conditions. Bioresponsive materials are materials that are exceptionally sensitive to biological signals or pathologies, such as pH, redox, enzymes, glucose, ions, hypoxia, and temperature, and can interact with or be stimulated by them. Smart biomaterials are a key stepping stone to the next generation of precision medicine. For example, when the human body is uninjured and the skin barrier remains intact, inherent antimicrobial properties are more suitable, eliminating the need to release antimicrobial agents into the tissue environment. However, when a wound occurs, the skin barrier is breached, and the body is directly exposed to pathogens, or even when infection has already occurred, relying solely on inherent antimicrobial fabrics contacting the tissue to kill bacteria is no longer the optimal solution. The primary option for controlling infection and alleviating symptoms is to release antimicrobial agents deep into the tissue to assist the immune system in eliminating invading pathogens. Therefore, bioresponsive antimicrobial finishing of cotton fabrics can more flexibly adapt to changes in the physiological environment and promote rapid recovery through more proactive response strategies. Summary of the Invention

[0006] To address the above issues, the present invention provides a bacteria-responsive hemostatic and antibacterial cotton fabric and its preparation method. This fabric is made by grafting a cationic hemostatic and antibacterial agent onto a base cotton fabric after oxidation via a phosphate bond. During normal use, the fabric maintains its hemostatic and antibacterial properties and exhibits excellent wash resistance. However, in the event of a bacterial infection, the phosphate bond breaks under the action of alkaline phosphatase secreted by the bacteria, thus achieving bacterial responsiveness. This releases the antibacterial agent into the tissue environment, killing deep-seated bacteria and promoting rapid wound healing.

[0007] To achieve the above objectives, the present invention provides the following technical solution, a bacteria-responsive hemostatic and antibacterial cotton fabric, and a 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 carboxyl groups;

[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-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 isomers thereof; 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, and 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 the oxidant solution for reaction, the solvent is water, the concentrations of the cotton fabric and the oxidant are 10-100 mg / mL and 0.1-50wt%, respectively, the oxidation temperature is 15-60°C, the oxidation pH is 1-10, the oxidation time is 8-48h, and the fabric is washed, dried and purified. The carboxyl content in the obtained oxidized cotton fabric is 0.05-0.35mmol / 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 amino groups and carboxyl groups, specifically comprising: first adding the oxidized cotton fabric to a solvent, adding a catalyst to activate the carboxyl groups in the oxidized cotton fabric for 1-2 hours, then adding the amino-modified phosphate to react, washing, drying and purification; 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 groups, respectively, 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, hyperbranched polylysine, and 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 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 and antibacterial cotton fabric with bacterial responsiveness is obtained.

[0016] The present invention has the following beneficial effects compared to the prior art:

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

[0018] 2. The present invention provides a bacteria-responsive hemostatic and antibacterial cotton fabric. 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 with bacterial infection, 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, quickly killing bacteria and accelerating tissue repair. DETAILED DESCRIPTION

[0020] The technical solutions of the present invention are further described below with reference to the following examples, but these examples are not intended to limit the present invention.

[0021] Example 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. The mixture was reacted at 25°C and pH = 6.8 for 12 h. The mixture was then 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, washed, dried and purified.

[0024] (3) 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 the fabric was 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] Example 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. The mixture was reacted at 25°C and pH = 6.8 for 12 h. The mixture was then 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) 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 the fabric was 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] Example 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. The mixture was reacted at 25°C and pH = 6.8 for 12 h. The mixture was then 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, washed, dried and purified.

[0034] (3) 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 the fabric was 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 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 phosphates; (2) oxidizing the base cotton fabric to obtain an oxidized cotton fabric containing carboxyl groups; (3) coupling the amino-modified phosphate obtained in (1) with the oxidized cotton fabric obtained in (2) through an amidation reaction between the amino group and the carboxyl group; (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; wherein: the cationic hemostatic antibacterial agent is at least one of chitosan, hyperbranched polylysine, quaternary ammonium salts or guanidine-based antibacterial agents containing amino groups, and the amino groups in the antibacterial agent and the amino groups in the phosphate-cotton fabric conjugate react under the action of a crosslinking agent to achieve the second step of coupling.

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, and 2-amino-1,3-propylene glycol.

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 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 the oxidant solution for reaction, the solvent is water, the concentrations of the cotton fabric and the oxidant are 10-100 mg / mL and 0.1-50wt% respectively, the oxidation temperature is 15-60°C, the oxidation pH is 1-10, the oxidation time is 8-48h, and the fabric is washed, dried and purified. The carboxyl content in the obtained oxidized cotton fabric is 0.05-0.35mmol / g.

5. The method for preparing a bacteria-responsive hemostatic and antibacterial cotton fabric according to claim 1, characterized in that: The step (3) specifically comprises: first adding oxidized cotton fabric to a solvent, adding a catalyst to activate the carboxyl groups in the oxidized cotton fabric for 1-2 hours, then adding amino-modified phosphate to react, washing, drying and purification; wherein the solvent is water, the carboxyl concentration is 5-10 mmol / mL, the molar ratio of carboxyl groups to amino groups 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 carboxyl groups, 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: In step (4), 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 group 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 4-24 hours. After washing, drying, packaging, and sterilization, a hemostatic and 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 the cotton fabric according to claim 7, characterized in that: Used in the preparation of medical supplies for wound hemostasis and / or infection protection.