CN114931661B

CN114931661B - Amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing and preparation method thereof

Info

Publication number: CN114931661B
Application number: CN202210426610.2A
Authority: CN
Inventors: 王萍; 李春明; 殷敬华
Original assignee: Shanghai Weigao Medical Technology Development Co ltd
Current assignee: Shanghai Weigao Medical Technology Development Co ltd
Priority date: 2022-03-28
Filing date: 2022-04-22
Publication date: 2024-01-09
Anticipated expiration: 2042-04-22
Also published as: CN114931661A

Abstract

The invention provides a preparation method of an amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing, which comprises the following steps: s1) wrapping an amphipathic amino acid polymer with positive charges on the surface of a nano rare earth oxide to obtain an amino acid/rare earth nanocrystal; s2) mixing the amino acid/rare earth nanocrystalline, hydrophilic polyol, isocyanate and hydrophilic dihydric alcohol, carrying out in-situ polymerization reaction, and curing to obtain the dressing. Compared with the prior art, the dressing provided by the invention can utilize the fluorescence responsiveness and antibacterial performance of rare earth nanocrystalline, and the sterilization and hydrophilicity of amino acid to realize performance superposition, so that the dressing not only has high-efficiency biocompatibility and antibacterial activity, but also has sensitive stimulus response to fluorescence, and can be used as a hydrophilic group real-time tracer material; meanwhile, the dressing has strong hydrophilicity, can effectively absorb wound seepage and maintain a healing environment with moderately moist wound; the obtained multifunctional dressing is suitable for curing serious wounds such as large-area burn, car accident and the like.

Description

Amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing and preparation method thereof

The present application claims priority from China patent office, application No. 202210312175.0, entitled "an amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing and method for its preparation", filed 28/03/2022, the entire contents of which are incorporated herein by reference.

Technical Field

The invention belongs to the technical field of medical dressing, and particularly relates to an amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing and a preparation method thereof.

Background

The medical dressing is used as an important sanitary material medical product, is used for covering a wound surface under the condition that skin is damaged, and plays roles of preventing excessive loss of in-vivo moisture and electrolyte, maintaining in-vivo environment stable, regulating body temperature, protecting the wound, preventing external microorganism invasion and the like, and preventing and reducing complications such as wound infection and the like before the skin is restored or rebuilt.

Tens of millions of people in China cause skin injury due to accidents or operations every year, and chronic wound surfaces such as pressure sores and ulcers closely related to the aged people are increased year by year along with the aging of population. According to statistics, the market demand of medical dressings in China reaches 400 hundred million yuan in 2010, and the annual average composite growth rate exceeds 20%. However, in medical dressings currently used in China, the market share of the traditional dressing is as high as more than 80%, and the market share of the novel dressing is far lower than that of European and developed countries. Compared with the traditional dressing, the novel dressing can improve the wound healing speed and healing quality, relieve pain, has lower replacement frequency and lower actual treatment cost, and meets the development requirements of modern wound care medicine. With the rapid development of the medical and health field in China and the improvement of the requirements of domestic patients on medical conditions and medical care levels, the novel medical dressing is favored by the patients and medical staff. Therefore, the medical dressing market in China is huge and the development is quite powerful.

At present, enterprises for producing novel medical dressings in China are few, the research and development investment of the enterprises is insufficient, the products are lack of competitiveness, most of novel medical dressing markets are occupied by expensive imported products (products of 3M, duPont, qiangsheng and other companies), great economic pressure is brought to domestic patients, and the quick improvement of wound nursing medical care level in China is also hindered.

Therefore, the research and development of the domestic novel medical dressing with excellent performance and acceptable price and independent intellectual property has very important significance for breaking monopoly and technical barriers of foreign products, promoting the development of the medical dressing industry in China, improving the medical experience of patients, and reducing the medical care cost of the patients and the working intensity of medical care workers.

Disclosure of Invention

In view of the above, the technical problem to be solved by the invention is to provide an amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing which has good biocompatibility, high efficiency and high antibacterial property and is hydrophilic and can be monitored in real time, and a preparation method thereof.

The invention provides a preparation method of an amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing, which comprises the following steps:

s1) wrapping an amphipathic amino acid polymer with positive charges on the surface of a nano rare earth oxide to obtain an amino acid/rare earth nanocrystal;

s2) mixing the amino acid/rare earth nanocrystalline, hydrophilic polyol, isocyanate and hydrophilic dihydric alcohol, carrying out in-situ polymerization reaction, and curing to obtain the amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing.

Preferably, the nano rare earth oxide is prepared according to the following steps:

a1 Mixing dendritic macromolecules and rare earth precursors in water, adding a precipitant, and performing ultrasonic treatment to obtain a suspension;

a2 Heating the suspension to perform hydrothermal reaction to obtain an intermediate product;

a3 Calcining the intermediate product to obtain the nano rare earth oxide.

Preferably, the dendrimer is a dendrimer PAMAM; the rare earth precursor is selected from lanthanum salt and/or yttrium salt; the precipitant is ammonia water; the mass ratio of the dendritic macromolecule to the rare earth precursor is (1-5): 1.

preferably, the adding speed of the precipitant is 0.5-2 ml/min; the power of the ultrasonic treatment is 200-300W; the ultrasonic treatment time is 0.5-1 h.

Preferably, the temperature of the hydrothermal reaction is 120-160 ℃; the hydrothermal reaction time is 4-8 hours; the calcining temperature is 600-800 ℃; the calcination time is 4-8 h.

Preferably, the amino acid monomer of the positively charged amphiphilic amino acid polymer is selected from one or more of L-phenylalanine, L-leucine, L-valine and L-alanine; the mass of the positively charged amphiphilic amino acid polymer is 5-10% of the mass of the nano rare earth oxide.

Preferably, the hydrophilic polyol is selected from polyester polyols and/or polyethylene glycols; the isocyanate is selected from 4, 4-diphenyl methane diisocyanate; the hydrophilic diol is selected from 1, 4-butanediol.

Preferably, the R value of the TPU is 0.95-1; the proportion of the hard segment is 0.3-0.5.

Preferably, the curing in step S2) is specifically: the temperature is kept at 70-85 ℃ for 1-3 h, 90-105 ℃ for 1-3 h, and 110-130 ℃ for 1-3 h.

The invention also provides the amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing prepared by the preparation method, and TPU is used as a matrix; the TPU is internally provided with nano rare earth oxide wrapped by amphiphilic amino acid polymer with positive charges.

The invention provides a preparation method of an amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing, which comprises the following steps: s1) wrapping an amphipathic amino acid polymer with positive charges on the surface of a nano rare earth oxide to obtain an amino acid/rare earth nanocrystal; s2) mixing the amino acid/rare earth nanocrystalline, hydrophilic polyol, isocyanate and hydrophilic dihydric alcohol, carrying out in-situ polymerization reaction, and curing to obtain the amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing. Compared with the prior art, the dressing provided by the invention can utilize the fluorescence responsiveness and antibacterial performance of rare earth nanocrystalline, and the sterilization and hydrophilicity of amino acid, so that performance superposition is realized, the dressing not only has high-efficiency biocompatibility and antibacterial activity (the antibacterial rate is more than 99.9%), but also has sensitive stimulation response to fluorescence, and can be used as a hydrophilic group real-time tracer material; meanwhile, the dressing has strong hydrophilicity (the swelling rate can reach 280 percent), can effectively absorb wound surface seepage and maintain a healing environment with moderately moist wound surface; the obtained multifunctional dressing is suitable for curing serious wounds such as large-area burns, car accidents and the like, and particularly for high-efficiency wound treatment under special conditions (such as war) in the background of the less flat world.

Drawings

FIG. 1 is a scanning electron microscope image of n-RE/AA obtained in example 2 of the present invention;

FIG. 2 is a scanning electron microscope image of the amino acid/rare earth nanocrystalline/TPU antimicrobial wound dressing obtained in example 2 of the present invention.

Detailed Description

The technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

The invention provides a preparation method of an amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing, which comprises the following steps: s1) wrapping an amphipathic amino acid polymer with positive charges on the surface of a nano rare earth oxide to obtain an amino acid/rare earth nanocrystal; s2) mixing the amino acid/rare earth nanocrystalline, hydrophilic polyol, isocyanate and hydrophilic dihydric alcohol, carrying out in-situ polymerization reaction, and curing to obtain the amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing.

The source of all the raw materials is not particularly limited, and the raw materials are commercially available or self-made.

In the present invention, the nano rare earth oxide is preferably lanthanum oxide and/or yttrium oxide; the nano rare earth oxide is preferably prepared by taking dendrimers as a template agent and adopting an ultrasonic-assisted precipitation method and a hydrothermal method, and more preferably is prepared according to the following steps: a1 Mixing dendritic macromolecules and rare earth precursors in water, adding a precipitant for ultrasonic treatment to obtain precipitate; a2 Heating the precipitate to perform hydrothermal reaction to obtain an intermediate product; a3 Calcining the intermediate product to obtain the nano rare earth oxide.

Mixing dendrimers with rare earth precursors in water; the dendrimer is preferably a dendrimer PAMAM; the rare earth precursor is preferably selected from lanthanum salts and/or yttrium salts, more preferably lanthanum nitrate and/or yttrium nitrate; the mass ratio of the dendritic macromolecule to the rare earth precursor is preferably (1-5): 1, more preferably (1.5 to 4): 1, more preferably (2 to 3): 1, a step of; the method of mixing is preferably ultrasound; the mass concentration of the dendritic macromolecules in the mixed solution is preferably 1-5%, more preferably 2-3%; the concentration of the rare earth precursor in the mixed solution is preferably 0.1mol/L to 0.5mol/L, more preferably 0.2mol/L to 0.4mol/L.

Then adding a precipitator for ultrasonic treatment to obtain a suspension; the precipitant is preferably ammonia water; the concentration of the ammonia water is preferably 0.2-0.75 mol/L; in the embodiment provided by the invention, the concentration of the ammonia water is specifically 0.2mol/L, 0.4mol/L, 0.6mol/L or 0.75mol/L; the molar ratio of the precipitant to the rare earth precursor is preferably 2:1 to 3:1, a step of; the adding speed of the precipitant is preferably 0.5-2 ml/min, more preferably 0.8-1.5 ml/min, and still more preferably 1-1.2 ml/min; in the invention, preferably adding a precipitant until no more precipitate is generated, and performing ultrasonic treatment; the power of the ultrasonic treatment is preferably 200-300W; the time of the ultrasonic treatment is preferably 0.5-1 h; the ultrasonic treatment is preferably performed at room temperature.

Heating the suspension to perform a hydrothermal reaction; the hydrothermal reaction is preferably carried out in an autoclave; the temperature of the hydrothermal reaction is preferably 120-160 ℃, more preferably 130-150 ℃ and still more preferably 140 ℃; the time of the hydrothermal reaction is preferably 4 to 8 hours, more preferably 5 to 7 hours, and still more preferably 6 hours; preferably centrifugally separating after hydrothermal reaction, washing and drying to obtain an intermediate product; the washing is preferably performed with ethanol; the drying temperature is preferably 120-160 ℃, more preferably 130-150 ℃, and even more preferably 140 ℃; the drying time is preferably 1 to 4 hours, more preferably 2 to 3 hours.

Calcining the intermediate product; the temperature of the calcination is preferably 600-800 ℃, more preferably 700-800 ℃, and still more preferably 750 ℃; the calcination time is preferably 4 to 8 hours, more preferably 4 to 7 hours, still more preferably 4 to 6 hours, and most preferably 5 hours. After calcination, grinding is preferred to obtain the nano rare earth oxide.

Wrapping the surface of the nano rare earth oxide with an amphipathic amino acid polymer with positive charges to obtain an amino acid/rare earth nanocrystal; the method of encapsulation is preferably a microcapsule method or a sol-gel method; the amino acid monomer of the positively charged amphiphilic amino acid polymer is preferably one or more of L-phenylalanine, L-leucine, L-valine and L-alanine; the mass of the positively charged amphiphilic amino acid polymer is preferably 5-10% of the mass of the nano rare earth oxide.

Mixing the amino acid/rare earth nanocrystalline, hydrophilic polyol, isocyanate and hydrophilic dihydric alcohol; the invention takes hydrophilic polyol as a soft segment, and isocyanate and hydrophilic dihydric alcohol as a hard segment; the hydrophilic polyol is preferably a polyester polyol and/or a polyethylene glycol; in the examples provided herein, the preferred molecular weight of the polyester polyol is specifically 2000; the molecular weight of the polyethylene glycol is specifically 2000-10000; the isocyanate is preferably 4, 4-diphenylmethane diisocyanate; the hydrophilic dihydric alcohol is preferably 1, 4-butanediol; the invention firstly uses amino acid to carry out surface modification treatment on rare earth nano oxide, then uses amino acid/rare earth nano crystal as modifier to initiate in-situ bulk polymerization of hydrophilic polyol, isocyanate and hydrophilic diol to obtain composite material, wherein the hydrophilic polyol, isocyanate and hydrophilic diol are polymerized to obtain TPU, and the proportion of each raw material is calculated according to the R value and the hard segment proportion of the TPU, wherein the R value of the TPU is preferably 0.95-1, more preferably 0.96-0.99, still more preferably 0.98-9.99; the hard segment ratio is preferably 0.3 to 0.5, more preferably 0.35 to 0.45, most preferably 0.4; in the invention, the amino acid/rare earth nanocrystalline and the hydrophilic polyol are preferably mixed, stirred and dehydrated under the conditions of heating and vacuum, and after ultrasonic treatment, isocyanate and hydrophilic dihydric alcohol are added; the heating temperature is preferably 90-115 ℃, more preferably 95-105 ℃, and still more preferably 100 ℃; the stirring and dehydrating time is preferably 1 to 5 hours, more preferably 2 to 4 hours, still more preferably 2 to 3 hours, and most preferably 2.5 hours; the temperature of the ultrasonic treatment is preferably 90-115 ℃, more preferably 95-105 ℃, and still more preferably 100 ℃; the power of the ultrasonic treatment is preferably 200-300W; the time of the ultrasonic treatment is preferably 10 to 60 minutes, more preferably 20 to 50 minutes, still more preferably 30 to 40 minutes.

Mixing and then carrying out in-situ polymerization reaction; the temperature of the in-situ polymerization reaction is preferably 100-140 ℃, more preferably 110-130 ℃, and still more preferably 120 ℃; the time of the in-situ polymerization is preferably 2 to 10 hours, more preferably 3 to 8 hours, still more preferably 3 to 6 hours.

After the reaction, curing to obtain the amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing; in the present invention, the curing is preferably specifically: preserving heat for 1-3 h at 70-85 ℃, preserving heat for 1-3 h at 90-105 ℃ and preserving heat for 1-3 h at 110-130 ℃; more preferably specifically: preserving heat for 1-3 h at 75-85 ℃, preserving heat for 1-3 h at 95-105 ℃ and preserving heat for 1-3 h at 115-130 ℃; the more preferred specific ones are: preserving heat for 1.5-2.5 h at 75-85 ℃, preserving heat for 1.5-2.5 h at 95-105 ℃ and preserving heat for 1.5-2.5 h at 115-130 ℃; the more preferred specific ones are: preserving heat for 2h at 75-85 ℃, preserving heat for 2h at 95-105 ℃ and preserving heat for 2h at 115-125 ℃; most preferably specifically: the temperature is kept at 80 ℃ for 2 hours, at 100 ℃ for 2 hours and at 120 ℃ for 2 hours.

The dressing provided by the invention can utilize the fluorescence responsiveness and antibacterial performance of rare earth nanocrystalline, and the sterilization and hydrophilicity of amino acid, so that performance superposition is realized, the dressing not only has high-efficiency biocompatibility and antibacterial activity (the antibacterial rate is more than 99.9%), but also has sensitive stimulation response to fluorescence, and the dressing can be used as a hydrophilic group real-time tracer material; meanwhile, the dressing has strong hydrophilicity (the swelling rate can reach 280 percent), can effectively absorb wound surface seepage and maintain a healing environment with moderately moist wound surface; the obtained multifunctional dressing is suitable for curing serious wounds such as large-area burns, car accidents and the like, and particularly for high-efficiency wound treatment under special conditions (such as war) in the background of the less flat world.

The invention also provides the amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing prepared by the method, and the dressing takes TPU as a matrix; the TPU is internally provided with nano rare earth oxide wrapped by amphiphilic amino acid polymer with positive charges.

In order to further illustrate the invention, the amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing and the preparation method thereof provided by the invention are described in detail below with reference to examples.

The reagents used in the examples below are all commercially available.

Example 1

1) 50ml of 0.2mol/L lanthanum nitrate hexahydrate solution is placed into a four-mouth flask and placed into an ultrasonic instrument by adopting a dendrimer PAMAM (molecular weight 14214.17, the addition amount is 2% of the mass of the solution) as a template agent and adopting an ultrasonic auxiliary precipitation method to combine a hydrothermal method, the temperature is adjusted to be 20+/-5 ℃, 0.2mol/L ammonia water precipitant is slowly added into the lanthanum nitrate solution by using a constant pressure funnel, the solution is dropwise added at the speed of 1ml/min until no precipitate is generated, and the flask is placed into the 200W ultrasonic instrument for continuous treatment for 1h and then is taken out. Transferring 60ml of the ultrasonic material into a hydrothermal kettle for further treatment, heating for 6 hours at 140 ℃, separating the obtained sample by using a centrifuge, washing for a plurality of times by using ethanol, taking out the sample, drying for 2 hours in a 140 ℃ oven, calcining for 5 hours at 750 ℃, grinding to obtain nano lanthanum oxide, and sealing and preserving.

2) Preparing 0.1mol/L of L-phenylalanine NCA solution, weighing 0.1g of nano lanthanum oxide as a core material, taking L-phenylalanine NCA as a capsule wall, adjusting the proportion of the core material to the capsule wall by a microcapsule method to ensure that the mass of the capsule wall is 10% of that of the core material, coating the surface of the nano lanthanum oxide prepared in the step 1) with the L-phenylalanine NCA, cleaning, freeze-drying and marking as n-RE/AA.

3) Vacuum stirring and dehydrating the polyester polyol PBA (2000) and the needle-shaped n-RE/AA prepared in the step 2) for 2.5 hours at 100 ℃, uniformly stirring, and carrying out ultrasonic treatment for 30 minutes at 100 ℃; the hard segment proportion is designed to be 0.4, the R value is 0.99, the mass of the small molecular chain extender 1, 4-Butanediol (BDO) 4, 4-diphenylmethane diisocyanate (MDI) is obtained, the needle-shaped n-RE/AA/PBA mixture is taken out and put into a beaker, BDO and MDI are sequentially added, and after rapid stirring is carried out uniformly, the mixture is poured into a dumbbell-shaped silica gel mold preheated at 120 ℃. After 3h, the bars were cured in an oven at 80℃for 2h, at 100℃for 2h, and at 120℃for 2h. And then naturally cooling the sample strip to obtain the amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing. And (5) standing for one week to test the performance.

And (3) detecting sterilization performance: according to the 2002 edition of the disinfection technical Specification, a disc diffusion method is adopted for detecting the disinfection performance. The test results show that the composite dressing has a killing rate of more than 99.999% on escherichia coli (8099 type), more than 99.999% on staphylococcus aureus (ATCC 6538 type), more than 99.999% on pseudomonas aeruginosa (ATCC 9027 type) and more than 99.999% on candida albicans (ATCC 10231 type).

Extracorporeal blood circulation coagulation experiment: the test protein adsorption amount is obviously reduced, the OD value and the cell compatibility are obviously improved, the protein adsorption amount is reduced from 1.62mg to 1.02mg of the pure TPU, and the OD value is reduced from 0.190 to 0.178, so that excellent blood compatibility and biocompatibility are shown.

Protein adsorption experiments: the BCA method protein concentration quantification kit is adopted. The albumin standard curve test method is as follows: standard protein samples were added to 24 well plates, 20 μl of quasiprotein sample and 100 μl of BCA were added per well, mixed well and stored in a sealed condition. And (3) naturally cooling after being placed for a period of time in a 37 ℃ environment, detecting an OD value (under ultraviolet light wave of 562 nm) by using an enzyme-labeled instrument, and obtaining a BCA standard curve, and calculating the concentration of the protein on the surface of the material according to the value. And placing the composite material film in a PBS buffer solution test tube dissolved with protein, then centrifuging, and measuring absorbance to obtain the protein adsorption quantity on the surface of the material.

MTT test: important means for determining the number of viable cells on the surface of a sample, growth and toxicity on the surface of a material. The principle is that the relative number and relative activity of living cells can be obtained according to the principle that only living cells can reduce MTT into formazan and crystallize and deposit, and the formazan is dissolved in DMSO and then the absorbance is measured. The specific method comprises the following steps: first, 1x1cm is taken ² Three films are placed in a 24-hole plate, then cell fluid is added into the films, and the films are placed for 24 hours in an environment containing carbon dioxide gas at 37 ℃; next, MTT was added to each well and allowed to stand for another 4 hours. Removing culture MTT solution, adding certain amount of culture solutionThe amount of DMSO was 5min. Finally, the absorbance at 570nm wavelength was measured to determine the relative number of living cells.

Cell proliferation: and observing the morphology, the number and the like of the cells on the surface of the material by adopting a laser scanning confocal microscope.

Swelling property test: the swelling ratio of the prepared n-RE/AA/TPU material is 228% by a weighing method test, and the material has excellent hydrophilicity.

Example 2

1) 50ml of 0.2mol/L lanthanum nitrate hexahydrate solution is placed in a four-mouth flask and placed in an ultrasonic instrument by using dendrimer PAMAM (molecular weight 14214.17) as a template agent and adopting an ultrasonic auxiliary precipitation method in combination with a hydrothermal method, the temperature is adjusted to 20+/-5 ℃, 0.4mol/L ammonia water precipitant is slowly added into the lanthanum nitrate solution by using a constant pressure funnel, the solution is dropwise added at a speed of 1ml/min, after no sediment is generated in the solution, titration is completed, continuous treatment is carried out for 1h by using a 200W ultrasonic instrument, and then the solution is taken out. Taking 60ml of white precipitate, adding into a high-pressure reaction kettle for further treatment, heating for 6 hours at 140 ℃, separating the obtained sample by a centrifugal machine, washing for a plurality of times by ethanol, taking out the sample, drying for 2 hours in a 140 ℃ oven, calcining for 5 hours at 750 ℃, grinding to obtain nano lanthanum oxide, and sealing and preserving.

2) Preparing 0.1 mol/L-leucine NCA solution, weighing 0.1g of nano lanthanum oxide as a core material, taking L-leucine NCA as a capsule wall, adopting a microcapsule method, adjusting the proportion of the core material to the capsule wall to ensure that the mass of the capsule wall is 10% of the mass of the core material, coating the surface of the nano lanthanum oxide prepared in the step 1) with the L-leucine NCA, cleaning, freeze-drying and marking as n-RE/AA.

The n-RE/AA obtained in example 2 was analyzed by a scanning electron microscope to obtain a scanning electron microscope image thereof, as shown in FIG. 1.

The amino acid/rare earth nanocrystalline/TPU antimicrobial wound dressing obtained in example 2 was analyzed by scanning electron microscopy to obtain a scanning electron microscopy image thereof, as shown in fig. 2.

And (3) detecting sterilization performance: according to the 2002 edition of the disinfection technical Specification, a disc diffusion method is adopted for detecting the disinfection performance. The test results show that the composite dressing has a killing rate of more than 99.99 percent on escherichia coli (8099 type), a killing rate of more than 99.999 percent on staphylococcus aureus (ATCC 6538 type), a killing rate of more than 99.999 percent on pseudomonas aeruginosa (ATCC 9027 type) and a killing rate of more than 99.999 percent on candida albicans (ATCC 10231 type).

Extracorporeal blood circulation coagulation experiment: the adsorption amount of the protein is obviously reduced, the OD value and the cell compatibility are obviously improved, the adsorption amount of the protein is reduced from 1.62mg to 0.93mg of pure TPU, and the OD value is reduced from 0.190 to 0.1703, so that the protein shows excellent blood compatibility and biocompatibility.

Swelling property test: the swelling ratio of the prepared n-RE/AA/TPU material is 250% by a weighing method test, and the material has excellent hydrophilicity.

Example 3

1) 50ml of 0.2mol/L gadolinium nitrate hexahydrate solution is placed in a four-mouth flask and placed in an ultrasonic instrument by using dendrimer PAMAM (molecular weight 14214.17, the addition amount is 2% of the mass of the solution) as a template agent and adopting an ultrasonic auxiliary precipitation method to combine a hydrothermal method, the temperature is adjusted to be 20+/-5 ℃, 0.6mol/L ammonia water precipitant is slowly added into lanthanum nitrate solution by using a constant pressure funnel, the solution is dropwise added at the speed of 1ml/min, titration is completed after no sediment is generated in the solution, the solution is continuously treated for 1h in a 200W ultrasonic instrument, and then the solution is taken out. Taking 60ml of white precipitate, adding into a high-pressure reaction kettle for further treatment, heating for 6 hours at 140 ℃, separating the obtained sample by a centrifugal machine, washing for a plurality of times by ethanol, taking out the sample, drying for 2 hours in a 140 ℃ oven, calcining for 5 hours at 750 ℃, grinding to obtain nano yttrium oxide, and sealing and preserving.

2) Preparing 0.1 mol/L-valine NCA solution, weighing 0.1g of nano yttrium oxide, coating the surface of the nano yttrium oxide prepared in the step 1) with L-valine NCA by a sol-gel method, wherein the content of the coated L-valine NCA is 10% of the mass of the nano yttrium oxide, and cleaning, freeze-drying and marking as n-RE/AA.

3) Vacuum stirring polyethylene glycol PEG5000 and needle-like n-RE/AA prepared in step 2) at 100deg.C for dehydration for 2.5h, stirring well, and ultrasonic treating at 100deg.C for 30min; the hard segment proportion is designed to be 0.4, the R value is 0.99, the mass of the small molecular chain extender 1, 4-Butanediol (BDO) 4, 4-diphenylmethane diisocyanate (MDI) is obtained, the needle-shaped n-RE/AA/PBA mixture is taken out and put into a beaker, BDO and MDI are sequentially added, and after rapid stirring is carried out uniformly, the mixture is poured into a dumbbell-shaped silica gel mold preheated at 120 ℃. After 3h, the bars were cured in an oven at 80℃for 2h, at 100℃for 2h, and at 120℃for 2h. And then naturally cooling the sample strip to obtain the amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing. And (5) standing for one week to test the performance.

And (3) detecting sterilization performance: according to the 2002 edition of the disinfection technical Specification, a disc diffusion method is adopted for detecting the disinfection performance. The test results show that the composite dressing has a killing rate of more than 99.99% for escherichia coli (8099 type), more than 99.9% for staphylococcus aureus (ATCC 6538 type), more than 99.9% for pseudomonas aeruginosa (ATCC 9027 type) and more than 99.99% for candida albicans (ATCC 10231 type).

Extracorporeal blood circulation coagulation experiment: the test protein adsorption amount is obviously reduced, the OD value and the cell compatibility are also obviously improved, the protein adsorption amount is reduced from 1.62mg to 0.63mg of the pure TPU, and the OD value is reduced from 0.190 to 0.1502, so that the excellent blood compatibility and biocompatibility are shown.

Swelling property test: the swelling ratio of the prepared n-RE/AA/TPU material is 180% by using a weighing method, and the material has good hydrophilicity.

Example 4

1) 50ml of 0.2mol/L gadolinium nitrate hexahydrate solution is placed in a four-mouth flask and placed in an ultrasonic instrument by using dendrimer PAMAM (molecular weight 14214.17, the addition amount is 2% of the mass of the solution) as a template agent and adopting an ultrasonic auxiliary precipitation method to combine a hydrothermal method, the temperature is adjusted to be 20+/-5 ℃, 0.75mol/L ammonia water precipitant is slowly added into lanthanum nitrate solution by using a constant pressure funnel, the solution is dropwise added at the speed of 1ml/min, after no sediment is generated in the solution, titration is completed, continuous treatment is carried out for 1h in a 200W ultrasonic instrument, and then the solution is taken out. Taking 60ml of white precipitate, adding into a high-pressure reaction kettle for further treatment, heating for 6 hours at 140 ℃, separating the obtained sample by a centrifugal machine, washing for a plurality of times by ethanol, taking out the sample, drying for 2 hours in a 140 ℃ oven, calcining for 5 hours at 750 ℃, grinding to obtain nano yttrium oxide, and sealing and preserving.

2) Preparing 0.1mol/L of L-alanine NCA solution, weighing 0.1g of nano yttrium oxide as a core material, taking L-alanine NCA as a capsule wall, adopting a microcapsule method, adjusting the proportion of the core material to the capsule wall to enable the mass of the capsule wall to be 10% of the mass of the core material, coating the surface of the nano yttrium oxide prepared in the step 1) with the L-alanine NCA, cleaning, freeze-drying and marking as n-RE/AA.

3) Vacuum stirring polyethylene glycol PEG10000 and needle-like n-RE/AA prepared in step 2) at 100deg.C for dehydration for 2.5h, stirring, and ultrasonic treating at 100deg.C for 30min; the hard segment proportion is designed to be 0.4, the R value is 0.99, the mass of the small molecular chain extender 1, 4-Butanediol (BDO) 4, 4-diphenylmethane diisocyanate (MDI) is obtained, the needle-shaped n-RE/AA/PBA mixture is taken out and put into a beaker, BDO and MDI are sequentially added, and after rapid stirring is carried out uniformly, the mixture is poured into a dumbbell-shaped silica gel mold preheated at 120 ℃. After 3h, the bars were cured in an oven at 80℃for 2h, at 100℃for 2h, and at 120℃for 2h. The bars were then naturally cooled. And (5) standing for one week to test the performance.

Extracorporeal blood circulation coagulation experiment: the test protein adsorption amount is obviously reduced, the OD value and the cell compatibility are also obviously improved, the protein adsorption amount is reduced from 1.62mg to 0.85mg of the pure TPU, and the OD value is reduced from 0.190 to 0.1621, so that the excellent blood compatibility and biocompatibility are shown.

Swelling property test: the swelling ratio of the prepared n-RE/AA/TPU material is 210% by a weighing method test, and the material has excellent hydrophilicity.

Comparative example

1) 50ml of a 0.2mol/L gadolinium nitrate hexahydrate solution is placed in a four-mouth flask and placed in an ultrasonic instrument by using dendrimer PAMAM (molecular weight 14214.17) as a template agent and adopting an ultrasonic auxiliary precipitation method in combination with a hydrothermal method, the temperature is adjusted to be 20+/-5 ℃, 0.75mol/L ammonia water precipitant is slowly added into a lanthanum nitrate solution by using a constant pressure funnel, the solution is dropwise added at a speed of 1ml/min, titration is completed after no sediment is generated in the solution, the solution is continuously treated for 1h in a 200W ultrasonic instrument, and then the solution is taken out. Taking 60ml of white precipitate, adding into a high-pressure reaction kettle for further treatment, heating for 6 hours at 140 ℃, separating the obtained sample by a centrifugal machine, washing for a plurality of times by ethanol, taking out the sample, drying for 2 hours in a 140 ℃ oven, calcining for 5 hours at 750 ℃, grinding to obtain nano yttrium oxide, and sealing and preserving.

2) Preparing 0.1mol/L polyvinyl alcohol K30, weighing 0.1g of nano yttrium oxide powder, adopting a microcapsule method to prepare the surface modified nano yttrium oxide in the step 1), cleaning, and freeze-drying.

3) Vacuum stirring polyethylene glycol PEG2000 and the surface modified rare earth gadolinium nanocrystalline prepared in the step 2) at 100 ℃ for dehydration for 2.5h, uniformly stirring, and carrying out ultrasonic treatment at 100 ℃ for 30min; the hard segment proportion is designed to be 0.4, the R value is 0.99, the mass of the small molecular chain extender 1, 4-Butanediol (BDO) 4, 4-diphenylmethane diisocyanate (MDI) is obtained, the needle-shaped n-RE/AA/PBA mixture is taken out and put into a beaker, BDO and MDI are sequentially added, and after rapid stirring is carried out uniformly, the mixture is poured into a dumbbell-shaped silica gel mold preheated at 120 ℃. After 3h, the bars were cured in an oven at 80℃for 2h, at 100℃for 2h, and at 120℃for 2h. And then naturally cooling the sample strip to obtain the amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing. And (5) standing for one week to test the performance.

And (3) detecting sterilization performance: according to the 2002 edition of the disinfection technical Specification, a disc diffusion method is adopted for detecting the disinfection performance. The test results show that the composite dressing has a killing rate of only 56.82% for escherichia coli (8099 type), 38.56% for staphylococcus aureus (ATCC 6538 type) and 43.14% for candida albicans (ATCC 10231 type).

Extracorporeal blood circulation coagulation experiment: the test protein adsorption amount is obviously reduced, the OD value and the cell compatibility are also obviously improved, the protein adsorption amount is reduced from 1.62mg to 1.28mg of the pure TPU, and the OD value is reduced from 0.190 to 0.1803, so that excellent blood compatibility and biocompatibility are shown.

Swelling property test: the swelling ratio of the prepared n-RE/PVA/TPU material is 158 percent by a weighing method, and the material has hydrophilicity.

Claims

1. The preparation method of the amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing is characterized by comprising the following steps:

s1) wrapping an amphipathic amino acid polymer with positive charges on the surface of a nano rare earth oxide to obtain an amino acid/rare earth nanocrystal; the wrapping method is a microcapsule method or a sol-gel method;

s2) mixing the amino acid/rare earth nanocrystalline, hydrophilic polyol and isocyanate with hydrophilic dihydric alcohol, carrying out in-situ polymerization reaction, and curing to obtain the amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing; the curing in the step S2) is as follows: preserving heat for 1-3 hours at 70-85 ℃, preserving heat for 1-3 hours at 90-105 ℃ and preserving heat for 1-3 hours at 110-130 ℃; the hydrophilic polyol is selected from polyester polyol and/or polyethylene glycol; the hydrophilic dihydric alcohol is selected from 1, 4-butanediol;

the nano rare earth oxide is prepared according to the following steps:

a3 Calcining the intermediate product to obtain nano rare earth oxide;

the dendritic macromolecule is dendritic macromolecule PAMAM; the rare earth precursor is selected from lanthanum salt and/or yttrium salt;

the mass ratio of the dendritic macromolecule to the rare earth precursor is (1-5): 1.

2. the method of claim 1, wherein the precipitant is aqueous ammonia.

3. The preparation method according to claim 1, wherein the adding speed of the precipitant is 0.5-2 ml/min; the power of the ultrasonic treatment is 200-300W; the ultrasonic treatment time is 0.5-1 h.

4. The method according to claim 1, wherein the hydrothermal reaction temperature is 120 ℃ to 160 ℃; the hydrothermal reaction time is 4-8 hours; the calcining temperature is 600-800 ℃; the calcination time is 4-8 hours.

5. The method of claim 1, wherein the amino acid monomers of the positively charged amphiphilic amino acid polymer are selected from one or more of L-phenylalanine, L-leucine, L-valine and L-alanine; the mass of the positively charged amphiphilic amino acid polymer is 5% -10% of the mass of the nano rare earth oxide.

6. The method of claim 1, wherein the isocyanate is selected from the group consisting of 4, 4-diphenylmethane diisocyanate.

7. The method according to claim 1, wherein the TPU has an R value of 0.95 to 1; the proportion of the hard segments is 0.3-0.5.

8. The amino acid/rare earth nanocrystalline/TPU antibacterial wound dressing prepared by the preparation method according to any one of claims 1 to 7, which is characterized in that TPU is taken as a matrix; the TPU is internally provided with nano rare earth oxide wrapped by amphiphilic amino acid polymer with positive charges.