A modified polylactic acid oligomer, and a preparation method and use thereof

Abstract

The application relates to a modified polylactic acid oligomer and a preparation method and application thereof. The modified polylactic acid oligomer has the structure shown in the following formula (I). The modified polylactic acid oligomer obtained by copolymerization of 5-hydroxy-2-hexenoic acid and lactic acid has more excellent and stable and persistent antibacterial activity, the antibacterial efficiency is greatly improved, the sterilization rate is improved, and the sterilization time is shortened; when the modified polylactic acid oligomer is applied to various antibacterial coatings and textile finishing, the surface no longer has a wet sticky feeling, the commercialization and wide application of the material are more beneficial, and the modified polylactic acid oligomer has higher affinity to a target substrate, so that the persistence, stability and washability of a surface coating can be improved.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of antibacterial materials, and particularly relates to a modified polylactic acid oligomer, a preparation method and application thereof, and particularly to the application of the modified polylactic acid oligomer in the fields of medicine, medical materials, textiles, sanitary products, environment, food, food packaging, dyeing and finishing auxiliaries, paint, surface coating, plastic and agricultural products. BACKGROUND

[0002] With the increasing demand for medical and health level, the demand for antibacterial materials is increasing. Current antibacterial materials mainly include inorganic, organic and natural antibacterial materials. The inorganic materials have high antibacterial efficiency, such as nano-silver antibacterial agent, but have low biological safety and cannot be degraded in the body; the organic antibacterial materials, such as biguanide organic compounds, have high toxicity and potential carcinogenicity; the natural antibacterial materials have good safety, but the production raw materials are complex, the antibacterial effect is unstable, and the antibacterial efficiency is low. The biodegradable materials based on polyhydroxyalkanoate, such as polylactic acid oligomer, have high biological safety, can balance safety, antibacterial efficiency and environmental protection, and are a kind of better antibacterial materials in line with the trend of sustainable development.

[0003] However, the polylactic acid oligomer as an antibacterial material still has some problems, such as the need for a relatively high dosage or concentration to achieve a high antibacterial rate and faster sterilization effect; if used for antibacterial coating or finishing agent, there is a problem of wet and sticky hand feeling; due to the low van der Waals force with the substrate, the washing resistance and stability are not good enough; due to its inherent biochemical properties, the antibacterial effect on some bacteria is weak. SUMMARY

[0004] Therefore, the purpose of the present application is to provide a modified polylactic acid oligomer to improve the antibacterial efficiency, practicability and stability of the polylactic acid oligomer, so that it can be more widely used.

[0005] The technical solutions for achieving the above-mentioned purposes include the following.

[0006] In a first aspect, the present application provides a modified polylactic acid oligomer having a structure as shown in the following formula (I),

[0007]

[0008] wherein n and m are independently selected from integers of 1-100.

[0009] The modified polylactic acid oligomer described in the present application is obtained by copolymerization of 5-hydroxy-2-hexenoic acid and lactic acid, and the number average molecular weight of the modified polylactic acid oligomer is 100-10000.

[0010] In a second aspect, the present application provides a method for preparing the modified polylactic acid oligomer, comprising the following steps:

[0011] The copolymerization reaction of 5-hydroxy-2-hexenoic acid and lactic acid is carried out under the protection of inert gas at a temperature of 100-300℃ and a pressure of 5Pa-5MPa, to obtain the modified polylactic acid oligomer.

[0012] Further, the method further comprises preparing 5-hydroxy-2-hexenoic acid, and the method for preparing 5-hydroxy-2-hexenoic acid comprises the following steps:

[0013] The reaction of 2,4-hexadienoic acid and water is carried out under acidic conditions, to obtain 5-hydroxy-2-hexenoic acid.

[0014] In a third aspect, the present application further provides the use of the modified polylactic acid oligomer in the preparation of an antibacterial agent.

[0015] In a fourth aspect, the present application further provides the use of the modified polylactic acid oligomer in the preparation of a preservative.

[0016] In a fifth aspect, the present application further provides the use of the modified polylactic acid oligomer in the preparation of a mite repellent.

[0017] In a sixth aspect, the present application further provides an antibacterial agent, wherein the active ingredient comprises the modified polylactic acid oligomer of the present application.

[0018] In a seventh aspect, the present application further provides a preservative, wherein the active ingredient comprises the modified polylactic acid oligomer of the present application.

[0019] In an eighth aspect, the present application further provides a mite repellent, wherein the active ingredient comprises the modified polylactic acid oligomer of the present application.

[0020] In a ninth aspect, the present application further provides the use of the modified polylactic acid oligomer or the antibacterial agent in the preparation of an antibacterial product.

[0021] In a tenth aspect, the present application further provides the use of the modified polylactic acid oligomer or the preservative in the preparation of a preservative product.

[0022] In an eleventh aspect, the present application further provides the use of the modified polylactic acid oligomer or the mite repellent in the preparation of a mite repellent product.

[0023] The bacteria can be bacteria (such as Staphylococcus aureus, Escherichia coli, etc.) or fungi (such as Candida albicans, etc.).

[0024] The antibacterial product is an antibacterial pharmaceutical preparation (such as a micro-needle, etc.), a textile, a paper towel, a laundry liquid, a food additive, a food packaging material, a dye, a dyeing finishing agent, a paint, a coating, a surface coating material, an agricultural product, or a livestock product, etc.; the antiseptic product is an antiseptic pharmaceutical preparation, a textile, a paper towel, a laundry liquid, a food additive, or a food packaging material, etc.; the acarid-removing product is a textile or a paper towel, etc.

[0025] The present application copolymerizes 5-hydroxy-2-hexenoic acid and lactic acid to obtain a modified polylactic acid oligomer, which has the following advantages compared with the polylactic acid oligomer:

[0026] (1) The modified polylactic acid oligomer has more excellent and stable antibacterial activity, and has a significant inhibitory effect on various bacteria, fungi, viruses, mites, bed bugs, and bugs. After modification, the synergistic antibacterial effect between materials is produced, the antibacterial efficiency is greatly improved, the sterilization rate is increased, the sterilization time is shortened, and more excellent antibacterial effect can be obtained with lower dosage or concentration and shorter time.

[0027] (2) After the modified polylactic acid oligomer is applied to various antibacterial coatings and textile finishing, the surface no longer has a wet sticky feeling, which is more beneficial to the commercialization and wide application of the material.

[0028] (3) The modified polylactic acid oligomer has higher affinity to the target substrate, which can improve the durability, stability, and washability of the surface coating. The antibacterial textile obtained after finishing with the modified polylactic acid oligomer can still maintain good antibacterial effect after many washes.

[0029] In addition, the modified polylactic acid oligomer of the present application has excellent antibacterial activity, biodegradability, biocompatibility, and other properties, and has the advantages of simple preparation process, low cost, high safety, and environmental friendliness, which is suitable for industrial production and large-scale use. It can be made into various forms or types of antibacterial materials, and can also be used in combination with other antibacterial materials or used to modify other materials to obtain antibacterial preparations and antibacterial materials with better performance, which greatly enriches the types and fields of antibacterial materials. BRIEF DESCRIPTION OF DRAWINGS

[0030] Figure 1 The infrared spectrum of 5-hydroxy-2-hexenoic acid.

[0031] Figure 2 The mass spectrum of 5-hydroxy-2-hexenoic acid.

[0032] Figure 3 The mass spectrum of the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomer prepared in Example 1.

[0033] Figure 4 Mass spectrum of poly(lactic acid-5-hydroxy-2-hexenoic acid) co-oligomer prepared for Example 5.

[0034] Figure 5 Infrared spectrum of poly(lactic acid-5-hydroxy-2-hexenoic acid) co-oligomer prepared for Example 5.

[0035] Figure 6 HPLC-MS chart of poly(lactic acid) oligomer prepared for Comparative Example 1.

[0036] Figure 7 Mass spectrum of poly(5-hydroxy-2-hexenoic acid) oligomer prepared for Comparative Example 2.

[0037] Figure 8 Infrared spectrum of poly(5-hydroxy-2-hexenoic acid) oligomer prepared for Comparative Example 2.

[0038] Figure 9 Tissue engineering microneedle based on poly(lactic acid-5-hydroxy-2-hexenoic acid) co-oligomer (A) and poly(lactic acid) oligomer (B).

[0039] Figure 10 Mass spectrum of solid poly(lactic acid) oligomer prepared for Example 7.

[0040] Figure 11 Comparison chart of microneedle prepared in Example 7 before and after effect on infected wound of SD rat.

[0041] Figure 12 Wound healing condition of SD rat after treatment with poly(lactic acid-5-hydroxy-2-hexenoic acid) co-oligomer on infected wound. DETAILED DESCRIPTION

[0042] In order to facilitate the understanding of the present application, a more comprehensive description of the present application will be given below. The present application can be realized in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present application more thorough and comprehensive.

[0043] The experimental methods in the following examples, unless otherwise specified, are generally carried out according to the conventional conditions or according to the conditions suggested by the manufacturers. The various common chemical reagents used in the examples are all commercially available products.

[0044] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in the description of the application herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used in this application, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0045] Furthermore, as used herein, the term "or" is the inclusive, not the exclusive, "or", and is equivalent to the term "and / or", unless the context clearly indicates otherwise. The term "based on" is not exclusive, and allows for other factors to be present, unless the context clearly indicates otherwise. Furthermore, throughout the specification, "one", "an", and "the" are used inclusively, meaning that "one" or "an", as well as "the", can refer to a single element, as well as a plurality of elements. "In" is inclusive, meaning "in" and "on".

[0046] At present, polylactic acid oligomers as an antibacterial material still have some problems, such as if a higher antibacterial rate and a faster sterilization effect are to be achieved, a relatively high dosage or concentration is required; if used for antibacterial coating or finishing agent, there is a problem of wet and sticky hand feeling; because the molecular weight is small, the van der Waals force with the substrate is low, so the washing resistance and stability are not good enough; because of its inherent biochemical properties, the antibacterial effect on some bacteria is weak. In order to overcome these problems and make polylactic acid oligomers more widely used, the present application researches and obtains a modified polylactic acid oligomer which can effectively improve the antibacterial efficiency, practicability and stability of polylactic acid oligomers.

[0047] In one embodiment of the present application, the present application provides a modified polylactic acid oligomer having a structure shown in the following formula (I),

[0048]

[0049] wherein n and m are independently selected from integers of 1-100.

[0050] In some embodiments, n is selected from integers of 1-50; and m is selected from integers of 1-50.

[0051] In some embodiments, n is selected from integers of 1-20; and m is selected from integers of 1-20.

[0052] In some embodiments, n is selected from integers of 1-12; and m is selected from integers of 1-12.

[0053] In some embodiments, n is selected from integers of 2-8; and m is selected from integers of 2-8.

[0054] In some embodiments, n is selected from integers of 1-6; and m is selected from integers of 1-6.

[0055] In some embodiments, n is selected from integers of 4-5; and m is selected from integers of 3-4.

[0056] In some embodiments, the modified polylactic acid oligomer has an average degree of polymerization of 2 to 100.

[0057] In some embodiments, the modified polylactic acid oligomer has an average degree of polymerization of 2 to 50.

[0058] In some embodiments, the modified polylactic acid oligomer has an average degree of polymerization of 2 to 12.

[0059] In some embodiments, the modified polylactic acid oligomer has an average degree of polymerization of 3 to 11.

[0060] In some embodiments, the modified polylactic acid oligomer has an average degree of polymerization of 4 to 9.

[0061] In some embodiments, the modified polylactic acid oligomer has an average degree of polymerization of 5 to 8.

[0062] In some embodiments, the modified polylactic acid oligomer has an average degree of polymerization of 7 to 8.

[0063] The modified polylactic acid oligomer of the present application can be obtained by copolymerization of 5-hydroxy-2-hexenoic acid and lactic acid, and has a number average molecular weight of 100 to 10,000.

[0064] In some embodiments, the mass ratio of 5-hydroxy-2-hexenoic acid to lactic acid is 1:0.5 to 3, preferably 1:0.8 to 2, more preferably 1:0.9 to 1.5, and more preferably 1:0.9 to 1.2.

[0065] In some embodiments, the modified polylactic acid oligomer has a number average molecular weight of 200 to 3,000, preferably 200 to 1,100, more preferably 200 to 800, more preferably 300 to 800, more preferably 400 to 800, and more preferably 600 to 700.

[0066] The modified polylactic acid oligomer of the present application can be obtained by conventional copolymerization of 5-hydroxy-2-hexenoic acid and lactic acid.

[0067] In one embodiment of the present application, the method for preparing the modified polylactic acid oligomer comprises the following steps:

[0068] The copolymerization of 5-hydroxy-2-hexenoic acid and lactic acid is carried out under inert gas protection at a temperature of 100°C to 300°C and a pressure of 5 Pa to 5 MPa to obtain the modified polylactic acid oligomer.

[0069] In one embodiment of the present application, the method for preparing the modified polylactic acid oligomer comprises the following steps: mixing 5-hydroxy-2-hexenoic acid and lactic acid, adding water, heating to reflux for 1-3 hours, and then performing a copolymerization reaction under the protection of inert gas at a temperature of 100-300°C and a pressure of 5 Pa-5 MPa to obtain the modified polylactic acid oligomer.

[0070] In some embodiments, the amount of water added is 4-8 times the total weight of 5-hydroxy-2-hexenoic acid and lactic acid, for example, 4, 5, 6, 7, or 8 times.

[0071] In some embodiments, the temperature is 150-250°C, preferably 180-220°C.

[0072] In some embodiments, the pressure is 1000-3000 Pa, preferably 1500-2500 Pa.

[0073] In some embodiments, the copolymerization reaction is performed for 0.01-72 hours, preferably 0.5-20 hours, preferably 0.5-16 hours, preferably 0.8-8 hours, more preferably 1-7 hours, more preferably 2-6 hours, and more preferably 3-5 hours.

[0074] In some embodiments, the method for preparing the modified polylactic acid oligomer further comprises preparing 5-hydroxy-2-hexenoic acid, and the method for preparing 5-hydroxy-2-hexenoic acid comprises the following steps:

[0075] In an acidic condition, 2,4-hexadienoic acid is reacted with water to obtain 5-hydroxy-2-hexenoic acid.

[0076] In some embodiments, the pH of the acidic condition is 1.0-4.0, preferably 2.0-3.5.

[0077] In some embodiments, the ratio of 2,4-hexadienoic acid to water is 1:10-20.

[0078] In some embodiments, 2,4-hexadienoic acid is reacted with water under heating and refluxing.

[0079] In some embodiments, 2,4-hexadienoic acid is reacted with water for 0.5-5 hours, preferably 1-3 hours.

[0080] In some embodiments of the present application, the use of the modified polylactic acid oligomer in the preparation of an antibacterial agent is also provided.

[0081] In some embodiments of the present application, the modified polylactic acid oligomer is also provided for use in preparing an antiseptic agent.

[0082] In some embodiments of the present application, the modified polylactic acid oligomer is also provided for use in preparing a mite repellent.

[0083] In some embodiments of the present application, an antibacterial agent is also provided, wherein the active ingredient of the antibacterial agent comprises the modified polylactic acid oligomer of the present application.

[0084] In some embodiments of the present application, an antiseptic agent is also provided, wherein the active ingredient of the antiseptic agent comprises the modified polylactic acid oligomer of the present application.

[0085] In some embodiments of the present application, a mite repellent is also provided, wherein the active ingredient of the mite repellent comprises the modified polylactic acid oligomer of the present application.

[0086] In some embodiments of the present application, the modified polylactic acid oligomer or the antibacterial agent is also provided for use in preparing an antibacterial product.

[0087] In some embodiments of the present application, the modified polylactic acid oligomer or the antiseptic agent is also provided for use in preparing an antiseptic product.

[0088] In some embodiments of the present application, the modified polylactic acid oligomer or the mite repellent is also provided for use in preparing a mite repellent product.

[0089] The bacteria can be bacteria (such as Staphylococcus aureus, Escherichia coli, etc.) or fungi (such as Candida albicans, etc.).

[0090] The antibacterial product can be an antibacterial pharmaceutical preparation (such as a microneedle, etc.), a textile, a paper towel, a laundry liquid, a food additive, a food packaging material, a dye, a dyeing finishing agent, a paint, a coating, a surface coating material, an agricultural product, or a livestock product, etc.; the antiseptic product can be an antiseptic pharmaceutical preparation, a textile, a paper towel, a laundry liquid, a food additive, or a food packaging material, etc.; the mite repellent product can be a mite repellent textile or a paper towel, etc.

[0091] The modified polylactic acid oligomer of the present application can be used alone or in combination with other antibacterial agents, antiseptic agents, or mite repellents, and can also be used to modify or reform other antibacterial materials, and can also be used as an active ingredient to prepare various forms or types of antibacterial materials with other additive ingredients, additive materials, auxiliary substances, etc., and can be applied in the fields of medicine, medical materials, textiles, sanitary products, the environment, food, food packaging, dyeing and finishing agents, paints, surface coatings, plastics, and agricultural products, etc.

[0092] The application will be further described in detail in connection with specific examples.

[0093] Example 1 Preparation of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer

[0094] (1) Preparation of 5-hydroxy-2-hexenoic acid

[0095] In a 500 ml round bottom flask, 2,4-hexadienoic acid 20 g and water 200 g were added, and concentrated sulfuric acid was added to adjust the pH of the solution to 2.0-2.5 under stirring; the mixed solution was heated to reflux at normal pressure for 2 hours. The reaction was cooled to room temperature, a small amount of sodium hydroxide was added to adjust the pH to 3-3.5, and the solution was filtered to obtain crystalline hydroxylated product (i.e. 5-hydroxy-2-hexenoic acid) 19.8 g, with a yield of 85%; the infrared data and mass spectrometry data thereof are shown in Figure 1 and Figure 2 .

[0096] (2) Preparation of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer

[0097] The 5-hydroxy-2-hexenoic acid prepared in step (1) was mixed with lactic acid monomer at a molar ratio of 1:1, 5 times the weight of water (5 times the total weight of 5-hydroxy-2-hexenoic acid and lactic acid) was added, heated to reflux for 2 hours, and then stirred and heated under the protection of nitrogen at a temperature of 200°C and a pressure of 2000 Pa for 4 hours of polymerization reaction, and then cooled to room temperature to obtain the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer.

[0098] After the reaction was completed, the temperature was lowered to room temperature, and the entire reaction product was collected, and the liquid chromatography-mass spectrometry graph thereof was obtained by a mass spectrometer, as shown in Figure 3 . This 2,4-hexadienoic acid copoly-modified polylactic acid oligomer (poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer) has both lactic acid monomer units with a repeating unit molecular weight of 72 (641, 713, 785, 857) and 2,4-hexadienoic acid monomer units with a repeating unit molecular weight of 112 (417, 529, 641), and its structural formula is shown in the following formula (I), with an average polymerization degree of 7-8, n=4-5, and m=3-4.

[0099]

[0100] Example 2 Preparation of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer

[0101] The preparation method of the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer provided in this example is different from that of example 1 in that the molar ratio of 5-hydroxy-2-hexenoic acid to lactic acid monomer is 1:2, and the others are the same as those of example 1.

[0102] Example 3 Preparation of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer

[0103] The preparation method of the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer provided in this example is different from that of Example 1 in that the molar ratio of 5-hydroxy-2-hexenoic acid to lactic acid monomer is 1:3, and the others are the same as those of Example 1.

[0104] Example 4 Preparation of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer

[0105] The preparation method of the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer provided in this example is different from that of Example 1 in that the polymerization time in step (2) is 1 hour, and the others are the same as those of Example 1.

[0106] Example 5 Preparation of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer

[0107] The preparation method of the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer provided in this example is different from that of Example 1 in that the polymerization time in step (2) is 16 hours, and the others are the same as those of Example 1, and the mass spectrum and infrared spectrum thereof are shown in Figure 4 and Figure 5

[0108] Preparation of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer

[0109] The lactic acid monomer was stirred and heated at 200°C under a pressure of 2000 Pa in a nitrogen atmosphere, and the polymerization reaction was carried out for 4 hours. After cooling to room temperature, the entire reaction product was collected to obtain the poly(lactic acid) oligomer. The liquid chromatography-mass spectrum thereof is shown in Figure 6 , the average polymerization degree is 4-5, and the molecular weight of the repeating unit is 72.

[0110] Preparation of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer

[0111] The 5-hydroxy-2-hexenoic acid monomer was stirred and heated at 200°C under a pressure of 2000 Pa in an acidic condition with pH=2-3 in a nitrogen atmosphere, and the polymerization reaction was carried out for 4 hours. After cooling to room temperature, the entire reaction product was collected to obtain the poly(lactic acid) oligomer. The mass spectrum and infrared spectrum thereof are shown in Figure 7 and Figure 8

[0112] Preparation of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer

[0113] ​​The monomers of lactic acid and glycolic acid are mixed in a molar ratio of 1:1, 5 times the weight of water is added, heated to reflux for 2 hours, then stirred and heated under the protection of nitrogen at a temperature of 200°C and a pressure of 2000 Pa, and the polymerization reaction is carried out for 4 hours. After cooling to room temperature, the entire reaction product is collected, and the poly(lactic acid-glycolic acid) copolymer is obtained.

[0114] Preparation of poly(lactic acid-3-carboxy-3-hydroxy glutaric acid) copolymer of Comparative Example 4

[0115] The monomers of lactic acid and 3-carboxy-3-hydroxy glutaric acid are mixed in a molar ratio of 1:1, 5 times the weight of water is added, heated to reflux for 2 hours, then stirred and heated under the protection of nitrogen at a temperature of 200°C and a pressure of 2000 Pa, and the polymerization reaction is carried out for 4 hours. After cooling to room temperature, the entire reaction product is collected, and the poly(lactic acid-3-carboxy-3-hydroxy glutaric acid) copolymer is obtained.

[0116] Preparation of poly(lactic acid-3-hydroxy butyric acid) copolymer of Comparative Example 5

[0117] The monomers of lactic acid and 3-hydroxy butyric acid are mixed in a molar ratio of 1:1, 5 times the weight of water is added, heated to reflux for 2 hours, then stirred and heated under the protection of nitrogen at a temperature of 200°C and a pressure of 2000 Pa, and the polymerization reaction is carried out for 4 hours. After cooling to room temperature, the entire reaction product is collected, and the poly(lactic acid-3-hydroxy butyric acid) copolymer is obtained.

[0118] Example 6: Test of antibacterial performance

[0119] In this example, the oligomers prepared in Examples 1-5 and Comparative Examples 1-5 are tested for antibacterial performance.

[0120] (1) The oligomers prepared in Examples 1-3 and Comparative Examples 1-5 are tested for antibacterial activity against Staphylococcus aureus (ATCC 6538) and Escherichia coli (ATCC 25922) according to the ASTM E2783-22 method. The results of the antibacterial performance are shown in Tables 1-2.

[0121] Table 1: Antibacterial performance of oligomers prepared with different monomer ratios

[0122]

[0123]

[0124] Table 2: Antibacterial performance of different polyhydroxyalkanoic acids

[0125]

[0126]

[0127] As can be seen from Table 1, the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer has very excellent antibacterial activity against Staphylococcus aureus and Escherichia coli. In addition, as the proportion of lactic acid copolymer in the copolymer increases, the antibacterial performance decreases, indicating that the copolymerization modification of 5-hydroxy-2-hexenoic acid copolymer on the polylactic acid oligomer can improve its antibacterial performance. And the antibacterial performance of poly(5-hydroxy-2-hexenoic acid) oligomer is worse than that of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer, indicating that 5-hydroxy-2-hexenoic acid and lactic acid copolymerization has a synergistic antibacterial effect, which can significantly improve the antibacterial performance of polylactic acid oligomer or poly(5-hydroxy-2-hexenoic acid) oligomer.

[0128] As can be seen from Table 2, the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer has better antibacterial performance than other kinds of modified polylactic acid oligomer materials.

[0129] (2) The antibacterial activity of the oligomers prepared in Examples 1-5 and Comparative Examples 1-5 against Candida albicans (ATCC10231) was detected, and the test method was ASTM E2149-20.

[0130] The test results are shown in Tables 3-5.

[0131] Table 3 Viscosity, degree of polymerization and antibacterial performance of oligomers prepared at different polymerization times

[0132]

[0133] Note: 0 hours in the table refers to the mixture of 5-hydroxy-2-hexenoic acid and lactic acid monomers mixed at a molar ratio of 1:1, i.e. the raw material mixture without reaction.

[0134] In the polymerization reaction, the polymerization time has a significant effect on the viscosity, degree of polymerization and antibacterial performance of the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer. As shown in Table 2, the viscosity and degree of polymerization increase with the extension of the polymerization time, while the antibacterial performance against Candida albicans (fungi) first increases and then decreases with the extension of the polymerization time, and the antibacterial performance of the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer prepared at a polymerization time of 4 hours is the best.

[0135] Table 4 Viscosity, degree of polymerization and antibacterial performance of oligomers prepared at different monomer ratios

[0136]

[0137]

[0138] Table 5 Antifungal activity of different polyhydroxyalkanoic acids against Candida albicans

[0139]

[0140] Example 7 Application of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer in tissue engineering microneedle

[0141] The poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer was obtained by polymerization for 16 hours according to the preparation method of Example 5. The obtained poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer product was poured into the mold of the tissue engineering microneedle, compacted and placed in the refrigerator for 18 hours, and then carefully taken out from the microneedle mold (A in Figure 9 The hardness of the obtained poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer product was tested to be 68 (Shore C hardness, -10°C). The mass spectrum of the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer was obtained by mass spectrometer, as shown in Figure 4 The degree of polymerization of the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer was about 6-30, and the molecular weight of the repeating unit was 72 and 112.

[0142] The poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer was obtained by polymerization for 16 hours according to the preparation method of Example 5. The obtained poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer product was poured into the mold of the tissue engineering microneedle, compacted and placed in the refrigerator for 18 hours, and then carefully taken out from the microneedle mold (A in Figure 9 The hardness of the obtained poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer product was tested to be 68 (Shore C hardness, -10°C). The mass spectrum of the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer was obtained by mass spectrometer, as shown in Figure 10 The degree of polymerization of the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer was about 6-30, and the molecular weight of the repeating unit was 72 and 112.

[0143] Treatment of infected wounds by microneedles: Before modeling, the test animals SD rats were shaved, and 1 cm diameter wounds were taken on the left and right sides of the back of each test animal using a skin punch, with a certain distance between the wounds to ensure that the wounds did not interfere with each other. Staphylococcus aureus (ATCC 6538) was diluted with physiological saline to the desired concentration for infection. After the infected wounds were dried (about 30 min), the microneedles were used to cover the wounds.

[0144] Through observation of the wounds, it was found that after one day, both the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer microneedle and the poly(lactic acid) oligomer microneedle would melt and be absorbed by the skin. The poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer microneedle melted and was absorbed faster, the wound was relatively dry, and the wound healed more easily, while the poly(lactic acid) oligomer microneedle melted slower and had not been completely absorbed by the skin, and the wound was slightly moist (as shown in Figure 11 It was shown that both of them could soften at body temperature of 37°C, and were easily absorbed by the tissue after administration. The poly(lactic acid-5-hydroxy-2-hexenoic acid) copolyoligomer had lower hardness and was more easily decomposed than the poly(lactic acid) oligomer.

[0145] The wound healing status after treatment with poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomers is as follows: Figure 12 As shown: After 11 days, the wounds treated with poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomers gradually scabbed over and healed, while the untreated mice died from systemic infection and sepsis due to high bacterial load in the wounds.

[0146] Example 8: Application of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomers in antibacterial textiles

[0147] The poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomer prepared in Example 1 and the polylactic acid oligomer prepared in Comparative Example 1 were used to perform antibacterial finishing on pure cotton nonwoven fabrics, with an application rate of 2% (relative to fabric weight). The antibacterial finishing process was a pad-drying process. The specific experimental steps are as follows:

[0148] Prepare a 2% concentration oligomer aqueous solution and pour it into the padding tank. Cut pure cotton woven fabric into 20cm*20cm pieces and immerse them in the padding tank. Pass the fabric through the rollers of a small padding machine (set the liquid absorption rate to 100%). After the rollers apply pressure, the oligomer can be evenly distributed on the pure cotton nonwoven fabric. After drying at 120℃ for 5 minutes, the antibacterial pure cotton nonwoven fabric is prepared.

[0149] Antibacterial pure cotton nonwoven fabric was tested against Escherichia coli (ATCC 25922) for 2 hours and 4 hours according to standard WS / T 650-2019. The antibacterial cotton nonwoven fabric treated with poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomer showed an antibacterial rate of 56.1% at 2 hours, indicating a certain antibacterial effect, and an antibacterial rate of 90.5% at 4 hours, achieving a good antibacterial effect. The pure cotton nonwoven fabric treated with unmodified polylactic acid oligomer showed an antibacterial rate of only 14.3% at 2 hours and 60.9% at 4 hours. This indicates that the antibacterial effect of unmodified polylactic acid oligomer is relatively poor, while the antibacterial cotton nonwoven fabric treated with poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomer has higher antibacterial efficiency and can shorten the time to achieve the same level of antibacterial effect.

[0150] The hand feel of the finished pure cotton nonwoven fabric was evaluated, and the evaluation criteria were divided into 1 to 5 levels, with level 5 being the best, smooth and not sticky; level 4 being smooth and slightly damp; level 3 being moderately damp and slightly frizzy; level 2 being relatively damp and frizzy; and level 1 being the worst, with severe and obvious dampness and frizz.

[0151] Table 6. Evaluation results of the hand feel of the finished pure cotton nonwoven fabric

[0152]

[0153]

[0154] As can be seen from Table 6, the antibacterial pure cotton nonwoven fabric obtained after finishing with the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomer has a smoother and more comfortable hand feeling than the pure cotton nonwoven fabric finished with the poly(lactic acid) oligomer not modified by copolymerization.

[0155] Example 9 Application of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomer in washable antibacterial textiles

[0156] The poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomer prepared in Example 1 and the poly(lactic acid) oligomer prepared in Comparative Example 1 were respectively used for antibacterial finishing of pure cotton woven fabric, with a dosage of 5% (relative to the weight of the fabric), and the antibacterial finishing process adopted was padding and baking, at a temperature of 120 degrees and for a time of 5 minutes. The specific experimental steps were as follows: two pieces of pure cotton woven fabric were cut into 20 cm*20 cm fabric, and were respectively padded with the aqueous solution (oligomer: water = 1:10) of the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomer prepared in Example 1 and the poly(lactic acid) oligomer prepared in Comparative Example 1, and were baked in a setting machine at 120°C for 5 minutes, with a fabric weight increase of about 5%, to obtain antibacterial finished pure cotton nonwoven fabric.

[0157] The antibacterial finished pure cotton nonwoven fabric was subjected to antibacterial testing on Staphylococcus aureus (ATCC 6538) according to the method shown in Table 7.

[0158] Table 7 Washable antibacterial testing of pure cotton woven fabric

[0159]

[0160]

[0161] As can be seen from Table 7, the antibacterial pure cotton woven fabric obtained after finishing with the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomer has very excellent antibacterial performance and good wash stability, and still has very high antibacterial rate after 50 times of washing, while the antibacterial performance of the pure cotton woven fabric finished with the poly(lactic acid) oligomer not modified by copolymerization is general, and the washability is poor, with an antibacterial rate of 0 after 50 times of washing. It can be seen that the antibacterial pure cotton woven fabric obtained after finishing with the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomer has better antibacterial performance and better wash stability than the pure cotton woven fabric finished with the poly(lactic acid) oligomer not modified by copolymerization.

[0162] Example 10 Application of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer oligomer in coatings

[0163] The poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer prepared in Example 1 and the unmodified polylactic acid oligomer prepared in Comparative Example 1 were mixed with polyacrylic acid sodium salt dispersant at a mass ratio of 1:3, respectively, and then the obtained mixture was added into a transparent water paint (consisting of polyacrylic acid sodium and water-based HDI curing agent at a mass ratio of 10:1) with a weight of 20 times the weight of the mixture, stirred and dispersed uniformly to obtain an antibacterial water paint.

[0164] The obtained antibacterial water paint was used to spray the wood board (spraying was performed using a spray gun, 70 ml per square meter was sprayed, and the air pressure was 2-3 bar), and after air drying, the antibacterial performance of the wood board against Escherichia coli (ATCC 25922) was tested according to ASTM E2149-20.

[0165] The results showed that the sterilization rates of the wood board coated with the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer and the wood board coated with the unmodified polylactic acid oligomer against Escherichia coli were 99.9% and 0%, respectively, indicating that the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer had very excellent antibacterial performance, and a low content of the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer added in the water paint could make the coating have excellent sterilization effect, while the unmodified polylactic acid oligomer added in the water paint at a low content could not make the obtained water paint coating have obvious antibacterial effect.

[0166] Example 11 Application of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer in acarid removal

[0167] The liquid poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer prepared in Example 1 and the unmodified liquid polylactic acid oligomer prepared in Comparative Example 1 were mixed with cotton for pillows at a proportion of 5% relative to the weight of the fabric, respectively, to prepare antibacterial fillers.

[0168] The acarid removal rate of the obtained antibacterial fillers was tested for 24 hours according to GB / T 24253, and the test results showed that the acarid removal rates of the antibacterial fillers containing the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer and the antibacterial fillers containing the unmodified polylactic acid oligomer were 71% and 30%, respectively, indicating that the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer had better acarid removal effect than the unmodified polylactic acid oligomer.

[0169] Example 12 Application of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer in laundry liquid

[0170] The liquid poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer prepared in Example 1 and the unmodified liquid polylactic acid oligomer prepared in Comparative Example 1 were added to a general laundry detergent (main ingredients: sodium dodecylbenzenesulfonate, alcohol ethoxysulfate, potassium laurate, and water) in an amount of 5% and 10% (with respect to the weight of the general laundry detergent), respectively, to obtain an antibacterial laundry detergent.

[0171] The antibacterial laundry detergent was tested for antibacterial activity against Escherichia coli (ATCC 25922) according to QB / T 2738 (bacteriostatic; simulation method), and the results are shown in Table 8.

[0172] Table 8: Antibacterial performance of antibacterial laundry detergent

[0173]

[0174]

[0175] As can be seen from Table 8, the laundry detergent added with the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer has a higher antibacterial rate than the general laundry detergent and the laundry detergent added with the polylactic acid oligomer.

[0176] Example 13: Application of poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer to a paper towel

[0177] The liquid poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer prepared in Example 1 and the unmodified liquid polylactic acid oligomer in Comparative Example 1 were applied to a general paper towel (ingredients: pure cotton, three-layer tissue) in an amount of 2.5%, 5%, and 7.5% (with respect to the weight of the paper towel) by the padding-drying process (the specific experimental method is the same as in Example 8) at a temperature of 120°C for 5 minutes to obtain an antibacterial paper towel.

[0178] The 28-day preservative performance of the obtained antibacterial paper towel against Escherichia coli (ATCC 25922) was tested according to the United States Pharmacopoeia USP 51 antimicrobial efficiency, and the results are shown in Table 9.

[0179] Table 9: Preservative performance of antibacterial paper towel

[0180]

[0181]

[0182] As can be seen from Table 9, the paper towel added with the poly(lactic acid-5-hydroxy-2-hexenoic acid) copolymer has a better preservative effect than the general paper towel and the paper towel added with the polylactic acid oligomer, and can meet the industrial requirement of <200 CFU / g of microbial colony count.

[0183] The above embodiments only express several implementation manners of the present application, and the description is relatively specific and detailed, but should not be understood as a limitation on the patent scope of the present application. It should be noted that, for ordinary skilled persons in the art, several modifications and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application should be subject to the appended claims.

Claims

1. A modified polylactic acid oligomer having a structure shown in the following formula (I), ###0001### wherein n and m are independently selected from an integer of 1 to 100. wherein n is selected from an integer of 1 to 50; and m is selected from an integer of 1 to 50.

2. The modified polylactic acid oligomer according to claim 1, wherein n is selected from an integer of 1 to 20; and m is selected from an integer of 1 to 20.

3. The modified polylactic acid oligomer according to claim 2, wherein n is selected from an integer of 1 to 12; and m is selected from an integer of 1 to 12.

4. The modified polylactic acid oligomer according to claim 3, wherein n is selected from an integer of 2 to 8; and m is selected from an integer of 2 to 8.

5. The modified polylactic acid oligomer according to claim 4, wherein n is selected from an integer of 4 to 5; and m is selected from an integer of 3 to 4.

6. The modified polylactic acid oligomer according to claim 5, characterized in that, The modified polylactic acid oligomer has a number average molecular weight of 100 to 10,000, which is obtained by a copolymerization reaction of 5-hydroxy-2-hexenoic acid and lactic acid.

7. A modified polylactic acid oligomer, characterized by, The 5-hydroxy-2-hexenoic acid and lactic acid have a molar ratio of 1 : 0.5 to 3.

8. The modified polylactic acid oligomer according to claim 7, characterized by The 5-hydroxy-2-hexenoic acid and lactic acid have a molar ratio of 1 : 0.8 to 2.

9. The modified polylactic acid oligomer according to claim 8, characterized in that, The 5-hydroxy-2-hexenoic acid and lactic acid have a molar ratio of 1 : 0.9 to 1.

5.

10. The modified polylactic acid oligomer according to claim 9, characterized in that, The 5-hydroxy-2-hexenoic acid and lactic acid have a molar ratio of 1 : 0.9 to 1.

2.

11. The modified polylactic acid oligomer according to claim 10, wherein The modified polylactic acid oligomer has a number average molecular weight of 200 to 3,000.

12. The modified polylactic acid oligomer according to any one of claims 7 to 11, characterized in that, The modified polylactic acid oligomer has a number average molecular weight of 200 to 1,100.

13. The modified polylactic acid oligomer according to any one of claim 12, characterized in that, The modified polylactic acid oligomer has a number average molecular weight of 200 to 800.

14. The modified polylactic acid oligomer according to any one of claim 13, characterized in that, The modified polylactic acid oligomer has a number average molecular weight of 300 to 800.

15. The modified polylactic acid oligomer according to any one of claim 14, characterized in that, The modified polylactic acid oligomer has a number average molecular weight of 400 to 800.

16. The modified polylactic acid oligomer of claim 15, wherein, The modified polylactic acid oligomer has a number average molecular weight of 600 to 700.

17. The modified polylactic acid oligomer of claim 16, wherein The method comprises the following steps:

18. A method for preparing the modified polylactic acid oligomer according to any one of claims 1 to 17, characterized by, The copolymerization reaction of 5-hydroxy-2-hexenoic acid and lactic acid is carried out under the protection of inert gas at a temperature of 100°C to 300°C and a pressure of 5 Pa to 5 MPa, so as to obtain the modified polylactic acid oligomer. The method comprises the following steps: mixing the 5-hydroxy-2-hexenoic acid and lactic acid, adding water, heating and refluxing for 1 to 3 hours, and then carrying out the copolymerization reaction of the 5-hydroxy-2-hexenoic acid and lactic acid under the protection of inert gas at a temperature of 100°C to 300°C and a pressure of 5 Pa to 5 MPa, so as to obtain the modified polylactic acid oligomer.

19. The method for preparing the modified polylactic acid oligomer according to claim 18, characterized in that, The water is added in an amount of 4 to 8 times of the total weight of the 5-hydroxy-2-hexenoic acid and lactic acid.

20. The method for preparing the modified polylactic acid oligomer according to claim 19, characterized in that, The temperature is 150°C to 250°C; and / or, 21. The method of producing a modified polylactic acid oligomer according to any one of claims 18 to 20, characterized in that, The pressure is 1,000 Pa to 3,000 Pa; and / or, The copolymerization reaction is carried out for 0.01 hour to 72 hours. The temperature is 180°C to 220°C.

22. The method for preparing the modified polylactic acid oligomer according to claim 21, characterized in that, The pressure is 1,500 Pa to 2,500 Pa.

23. The method for preparing the modified polylactic acid oligomer according to claim 21, characterized in that, The copolymerization reaction is carried out for 0.5 hour to 20 hours.

24. The method for preparing the modified polylactic acid oligomer according to claim 21, characterized in that, The copolymerization reaction is carried out for 0.5 hour to 16 hours.

25. The method for preparing the modified polylactic acid oligomer according to claim 24, characterized in that, The copolymerization reaction is carried out for 0.8 hour to 8 hours.

26. The method for preparing the modified polylactic acid oligomer according to claim 25, characterized in that, The copolymerization reaction is carried out for 1 hour to 7 hours.

27. The method for preparing the modified polylactic acid oligomer according to claim 26, characterized in that, The copolymerization reaction is carried out for 2 hour to 6 hours.

28. The method for preparing the modified polylactic acid oligomer according to claim 27, characterized in that, The copolymerization reaction is carried out for 3 hour to 5 hours.

29. The method for preparing the modified polylactic acid oligomer according to claim 28, characterized in that, The method further comprises the following steps of preparing 5-hydroxy-2-hexenoic acid.

30. The method of producing a modified polylactic acid oligomer according to any one of claims 18 to 20, characterized in that, The 5-hydroxy-2-hexenoic acid is obtained by reacting 2,4-hexadienoic acid with water under acidic conditions. The pH of the acidic conditions is 1 to 4; and / or, 31. The method for preparing the modified polylactic acid oligomer according to claim 30, characterized in that, ​ The mass ratio of the 2,4-hexadienoic acid and water is 1:10-20; and / or, The 2,4-hexadienoic acid and water are reacted under the condition of heating reflux; and / or, The reaction time of the 2,4-hexadienoic acid and water is 0.5-5 hours.

32. Use of the modified polylactic acid oligomer according to any one of claims 1-17 in the preparation of an antibacterial agent, a preservative, or a mite-removing agent.

33. An antimicrobial, antiseptic, or antiacarid agent, characterized in that, The active ingredient of which contains the modified polylactic acid oligomer according to any one of claims 1-17.

34. Use of the modified polylactic acid oligomer according to any one of claims 1-17 or the antibacterial agent according to claim 33 in the preparation of an antibacterial product; or, Use of the modified polylactic acid oligomer according to any one of claims 1-17 or the preservative according to claim 33 in the preparation of a preservative product; or Use of the modified polylactic acid oligomer according to any one of claims 1-17 or the mite-removing agent according to claim 33 in the preparation of a mite-removing product.

35. The use according to claim 32 or 34, characterized in that The bacteria are bacteria or fungi.

36. The use according to claim 35, wherein The bacteria are Staphylococcus aureus or Escherichia coli.

37. The use of claim 35, wherein, The fungi are Candida albicans.

38. The use of claim 34, wherein, The antibacterial product is a pharmaceutical preparation, a textile, a paper towel, a laundry liquid, a food additive, a food packaging material, a dye, a dyeing finishing agent, a paint, a coating, a surface coating material, an agricultural product, or a livestock product that can resist bacteria; The preservative product is a pharmaceutical preparation, a textile, a paper towel, a laundry liquid, a food additive, or a food packaging material that can resist bacteria; The mite-removing product is a textile or a paper towel that can remove mites.

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