CN118252985A - Tea polyphenol bionic gastrostomy tube coating and preparation method thereof - Google Patents

Tea polyphenol bionic gastrostomy tube coating and preparation method thereof Download PDF

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CN118252985A
CN118252985A CN202410668400.3A CN202410668400A CN118252985A CN 118252985 A CN118252985 A CN 118252985A CN 202410668400 A CN202410668400 A CN 202410668400A CN 118252985 A CN118252985 A CN 118252985A
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gastrostomy tube
tea polyphenol
solution
coating
tube coating
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CN118252985B (en
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张海军
张超
李艳君
罗涛
崔晓珊
敖国昆
袁坤山
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Shandong Branden Medical Devices Co Ltd
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Shandong Branden Medical Devices Co Ltd
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    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
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Abstract

The invention discloses a tea polyphenol bionic gastrostomy tube coating and a preparation method thereof. The coating is internally coated with tea polyphenol powder, tea polyphenol nano particles and ascorbic acid, so that the antibacterial and acid-resistant effects are achieved, wherein the added ascorbic acid can effectively prevent degradation of tea polyphenol, and the coating prepared by the method has excellent antibacterial and corrosion-resistant properties, has good biocompatibility and has good application prospect in the field of gastrostomy tube coatings.

Description

Tea polyphenol bionic gastrostomy tube coating and preparation method thereof
Technical Field
The invention belongs to the field of biomedical materials, and particularly relates to a tea polyphenol bionic gastrostomy tube coating and a preparation method thereof.
Background
Gastrostomy tubes provide a feeding path for patients who cannot take or swallow food, and are critical for patients suffering from severe dysphagia, gastrointestinal diseases or other health problems. However, the gastrostomy tube is easy to grow bacteria in the long-term use process, the risk of infection of the gastrostomy tube is extremely high, pain and discomfort are brought to patients, and the treatment effect is reduced. The antibiotics are used for preventing or treating fistulization in clinic, so that the effect of the fistulization is better, but the long-term use can cause the generation of drug-resistant bacteria, so that the treatment becomes more difficult. In addition, the gastrostomy tube is easy to break after being continuously used for more than 6 months, mainly caused by corrosion caused by long-term contact with gastric acid, which reduces the safety of the gastrostomy tube in use and has a certain adverse effect on the health of patients.
An antibacterial coating is coated on the surface of the fistulization tube, wherein the released active ingredient can inhibit the proliferation of bacteria around the tube, and effectively reduce the complications related to infection. Meanwhile, the use of the corrosion-resistant coating can prolong the service life of the pipeline, reduce the frequency of replacing the pipeline, reduce the medical cost of patients and reduce the medical cost.
Tea Polyphenol (TP) has various biological functions such as antioxidation, antibiosis and the like, and the characteristics lead the tea polyphenol to have potential application value in the field of medical care. The antibacterial effect of tea polyphenols can be exerted by inhibiting the adhesion and colonization of pathogenic bacteria, and is mainly attributed to the main components in tea polyphenols, such as catechin, caffeic acid, etc., which can interfere with the cell membrane structure of microorganisms and inhibit the biosynthesis pathway thereof, thereby achieving the effect of inhibiting the growth of microorganisms. And tea polyphenols have a certain acid resistance, which makes them able to maintain a certain activity in the environment of gastric acid, thus having a certain promoting effect against gastrointestinal infections and digestive tract diseases. In addition, the tea polyphenol also has an antioxidation effect, can remove free radicals, and slow down the aging process of the surface materials of the medical instrument, so that the service life of the medical instrument is prolonged, and the medical cost is reduced.
Patent CN202220456495.9 discloses a multifunctional gastrostomy tube which can effectively prevent the mechanical expansion of the gastrostomy orifice and reduce the possibility of the mouth-feel staining of the gastrostomy orifice, but has no inhibiting effect on bacteria already existing in the gastrostomy orifice. Patent cn20221127935. X discloses a gastrostomy tube, the surface of which is coated with a lipopolysaccharide compound and is coated with a medicament for promoting wound repair and an antibacterial and anti-inflammatory medicament, and a medicament-carrying film-coated catheter is prepared by an electrostatic spraying technology, but the coating prepared by the method has no corrosion resistance, the effect is single, and the medicament-carrying film formed by electrostatic spraying deposition is rough, so that a patient may have a strong foreign body sensation. Patent CN202310600809.7 discloses a preparation method of a double-component hydrogel lubricating coating on the surface of a nasogastric tube, and the prepared double-component hydrogel lubricating coating has good hydrophilic lubricating property and excellent combination stability with the surface of the nasogastric tube, has no acid-resistant and antibacterial effects, and still has the problems of corrosion, infection and the like in the long-term use process of the nasogastric tube. At present, the gastrostomy tube coating has single function, and has the functions of bacteriostasis, corrosion resistance and the like, and no report is made on the gastrostomy tube.
Disclosure of Invention
Aiming at the defects of the prior gastrostomy tube in terms of antibacterial and corrosion resistance, the invention provides a tea polyphenol bionic gastrostomy tube coating and a preparation method thereof, wherein the bionic coating is formed by compounding a plurality of layers of TP-gel coatings, the TP-gel coatings mainly comprise hydrogel, TP powder, tea polyphenol nano particles (TP-NPs) and ascorbic acid, and the coating has good corrosion resistance and antibacterial effects and improves the clinical application effect of the gastrostomy tube. The invention solves four technical problems: (1) Aiming at the defect that the antibiotic medicine is easy to generate drug resistance, TP is adopted to optimize the antibacterial effect of the gastrostomy tube coating, TP powder is directly added into hydrogel, TP component is slowly released in the hydrogel, and the continuous anti-infection effect is achieved; (2) Solving the problem of weak gastric acid corrosion resistance of the gastrostomy tube, applying TP to the hydrogel coating in the form of nano particles (namely TP-NPs), wherein the TP is wrapped in the nano particles without release, thereby playing roles in acid resistance and corrosion resistance; (3) To avoid oxidation of TP during coating preparation or storage, ascorbic acid is added as a reducing agent; (4) For the problem that a single-layer coating falls off and fails, the invention imitates the tea scale deposition principle, and prepares a plurality of layers of ultrathin TP-gel coatings on the surface of the gastrostomy tube to form a tea polyphenol bionic coating, thereby further improving TP carrying capacity and enhancing antibacterial and corrosion-resistant effects.
The invention aims at realizing the following technical scheme:
As shown in fig. 1, (1) the surface of the gastrostomy tube coating section is firstly ultrasonically cleaned with methanol and deionized water, then dried under nitrogen flow, soaked in 10-30wt.% benzophenone/ethanol solution for 2 min after the treatment is completed, washed with methanol for 3 times, and dried again under nitrogen flow;
(2) Immersing the gastrostomy tube coating section in a degassed gel pre-solution consisting of 0.5-1.5wt.% TP powder, 0.5-1.5wt.% TP-NPs, 0.5-1wt.% ascorbic acid, 23wt.% hydrogel monomer, 0.05wt.% crosslinker and 0.2wt.% photoinitiator;
(3) Forming a TP-gel coating by Ultraviolet (UV) irradiation;
(4) Flushing the surface of the gastrostomy tube with a buffer solution to remove the uncrosslinked hydrogel monomer and the ungrafted polymer;
(5) Repeating the step (2), the step (3) and the step (4), and laminating and assembling the TP-gel coating until the number of layers reaches the required number, and marking the number as n, thereby obtaining the tea polyphenol bionic coating.
Further, the gastrostomy tube coating section in the step (1) is ultrasonically cleaned by methanol and deionized water, the cleaning time is 5-15 min, and the frequency is 20-60 kHz.
Further, the gastrostomy tube material in the step (1) is silicone rubber, and because the silicone rubber material has a hydrophobic property, the surface of the gastrostomy tube needs to be modified so that the surface of the gastrostomy tube can be grafted with a hydrogel polymer, 10-30% of benzophenone/ethanol is used as a photoinitiator, and the polymerization reaction is initiated by UV irradiation in the step (3), so that the surface of the gastrostomy tube can be covalently crosslinked with the hydrogel polymer.
Further, the degassing method in the step (2) is one of ultrasonic degassing, vacuum degassing and helium blowing degassing, and the gel pre-solution is degassed, so that bubbles in the liquid can be removed, and the TP-gel coating is prevented from being roughened and damaged.
Further, in the step (2), the photoinitiator is Irgacure2959, the hydrogel monomer is acrylamide, the cross-linking agent is N, N-methylene bisacrylamide, lrgacure 2959 is a water-soluble photoinitiator, benzoyl free radicals and carbonyl free radicals are generated through alpha-fracture under illumination, and both free radicals can initiate polymerization of the monomer acrylamide and the cross-linking agent N, N-methylene bisacrylamide, and TP powder, TP-NPs and ascorbic acid can be wrapped in the process to form a TP-gel coating. The TP-NPs of the TP-gel coating are only wrapped in the gel without release due to the chitosan surface layer, so that the purpose of long-term acid resistance can be achieved, and TP powder is directly wrapped in the gel, so that the TP-NPs can play an antibacterial role in the slow release process. In addition, the added ascorbic acid can prevent TP from being oxidized and failed as a reducing agent.
Further, the preparation method of the TP-NPs in the step (2) comprises the following steps: at room temperature and stirring speed of 600 r/min, dropwise adding 10 mL of 2 g/L gamma-polyglutamic acid into 50 mL of 1 g/L chitosan-acetic acid buffer solution with pH of 2.5 by using a microinjection pump at the speed of 6 mL/h, continuously stirring 12 h, and dialyzing to remove unbound small molecular polymer to obtain the gamma-polyglutamic acid/chitosan carrier with negative charges on the surface; then 5 mL of 2 g/L aqueous solution of tea polyphenol is injected into the gamma-polyglutamic acid/chitosan carrier according to the speed of 10 mL/h, the mixture is transferred into a dialysis bag after being stirred for overnight, the solution is dialyzed by 10 mmol/L citric acid buffer solution with the pH of 2.5 to remove unbound free drug molecules, the buffer solution is replaced at intervals of 1 h until the ultraviolet absorption of the tea polyphenol is not detected in the solution outside the dialysis bag, and the solution in the dialysis bag is freeze-dried to obtain tea polyphenol nano particles with the particle size of 200-300 nm.
The TP-NPs prepared by the method have good pH response and drug release control capacity, because gamma-polyglutamic acid contains abundant free carboxyl groups, chitosan contains a large amount of free amino groups, and strong electrostatic attraction exists between the amino groups and the carboxyl groups, so that the nano particles have compact structures, the structures can be maintained stable under the gastric acid condition, and 75% of tea polyphenol can be prevented from being released.
Specifically, the TP-NPs have a TP content of 26-27% and a particle size of 350-450 nm.
Further, in the step (3), UVP CL-1000 is adopted for irradiation, the wavelength is set to be 365 nm, the power is 30W, and the duration is 30-90 min.
Further, in the step (4), the buffer solution washes the surface of the gastrostomy tube for 20-40min hours, and the uncrosslinked hydrogel monomer and the ungrafted polymer are removed, so that the connection between the TP-gel coating layers can be more compact.
Preferably, in the step (5), the number of layers n of the TP-gel coating is 2-8, and the thickness of each layer is 10-15 μm, and further, n may be selected and adjusted according to the actual needs of the required TP load amount, and the number of layers n is at least 2, for example, 2,3,4, 5, 6,7, and 8 layers, which may meet the requirements.
The tea polyphenol bionic gastrostomy tube coating is prepared by the preparation method.
The application provides a bionic gastrostomy tube coating and a preparation method thereof, which have the following advantages:
1. The invention solves the problems of no bacteria resistance and no corrosion resistance in the use of the gastrostomy tube by adding TP, and the TP-gel coating comprises TP in two different states, one is TP powder which is directly and slowly released, thereby playing an antibacterial role; the other is TP-NPs in a nanoparticle state, most of TP is wrapped in the nanoparticles and not consumed, and a TP protective layer is formed on the surface of the gastrostomy tube, so that the TP-NPs have the function of gastric acid resistance.
2. In order to prevent TP from being oxidized in the preparation and storage processes of the gastrostomy tube coating, the ascorbic acid is added into the gel pre-solution to serve as a reducing agent, so that the stability and the bioactivity of TP are effectively prolonged.
3. According to the invention, a multi-layer ultrathin TP-gel coating is prepared on the surface of the gastrostomy tube to form a tea polyphenol bionic coating according to the tea scale deposition principle, so that the TP loading capacity is further improved, and the acid resistance and corrosion resistance are optimized.
4. According to the invention, the TP-gel coating is overlapped to form the tea polyphenol bionic coating, and the TP-gel coating can be adjusted within the layer number range of 2-8 layers according to different requirements, so that clinical requirements are met.
The tea polyphenol bionic coating prepared by the invention has antibacterial and corrosion-resistant effects, and the raw materials used are safe and harmless, the process is simple, the cost is low, and the coating is uniform and complete.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention.
FIG. 1 is a schematic diagram of the preparation of a tea polyphenol biomimetic coating of the present invention;
FIG. 2 is a graph showing the cumulative percent release of TP in the coatings of example 1 and comparative examples 1-4 in accordance with the present invention;
FIG. 3 is a schematic illustration of the results of the coating bacteriostasis experiments of example 1 and comparative examples 1-3 in the present invention;
FIG. 4 is a schematic representation of the cytotoxicity test results of the coatings of example 1 and comparative example 1 according to the present invention.
Detailed Description
Example 1
The preparation method comprises the following specific steps of:
(1) Preparation of TP-NPs: at room temperature and stirring speed of 600 r/min, dropwise adding 10 mL of 2 g/L gamma-polyglutamic acid into 50mL of 1.0 g/L chitosan acetic acid buffer solution with pH of 2.5 by using a microinjection pump at the speed of 6 mL/h, continuously stirring 12 h, and dialyzing to remove unbound small molecular polymer to obtain the gamma-polyglutamic acid/chitosan carrier with negative charges on the surface; then 5mL of 2 g/L aqueous solution of tea polyphenol is injected into a gamma-polyglutamic acid/chitosan carrier according to the speed of 10 mL/h, stirred overnight and transferred into a dialysis bag, 10 mmol/L of citric acid buffer solution with the pH of 2.5 is used for dialysis to remove unbound free drug molecules, the buffer solution is replaced by 1 h at intervals until no ultraviolet absorption of tea polyphenol is detected in the solution outside the dialysis bag, the solution in the dialysis bag is dried for 15 h under the conditions of the vacuum degree of more than 0.1 mmHg and the temperature of minus 30 ℃, and then the solution is dried for 8 h under the conditions of the vacuum degree of more than 0.1 mmHg and the temperature of 10 ℃ to obtain TP-NPs for later use.
(2) The gastrostomy tube coating section was ultrasonically cleaned with methanol and deionized water, respectively, 10min, at an ultrasonic frequency of 40: 40 kHz, and then blown to a surface dry state, about 3: 3 min, with a nitrogen dry blowing instrument.
(3) Immersing the dried gastrostomy tube coating section into a benzophenone/ethanol solution containing 20wt.% for 2 min times, taking out, washing in a methanol solution for 3 times uniformly, and blowing to a surface dry state by a nitrogen dry blowing instrument.
(4) 1G TP powder, 1g TP-NPs and 0.75 g ascorbic acid are weighed and fully dissolved in 74 ml purified water, then 23 g hydrogel monomer acrylamide, 0.05 g cross-linking agent N, N-methylene bisacrylamide and 0.2 g photoinitiator Irgacure2959 are sequentially added, after the complete dissolution, gel pre-solution is prepared, and the gel pre-solution is subjected to ultrasonic degassing under the conditions of 43 kHz and 5kPa for 20 min.
(5) Immersing the gastrostomy tube coating section treated in the steps (2) and (3) into the gel pre-solution fully, taking out, and then adopting UVP CL-1000 to irradiate, setting the wavelength to 365 nm, the power to 30W and the duration to 60min, thereby forming a first TP-gel coating layer.
(6) The TP-gel coating was rinsed thoroughly with buffer at about 30 min to remove the uncrosslinked hydrogel polymer solution.
(7) Repeating the operations of the steps (5) and (6) until 5 layers of TP-gel coating are formed, and then the tea polyphenol bionic coating is prepared.
Example 2
The preparation method comprises the following specific steps of:
(1) Preparation of TP-NPs: at room temperature and stirring speed of 600 r/min, dropwise adding 10 mL of 2 g/L gamma-polyglutamic acid into 50mL of 1.0 g/L chitosan acetic acid buffer solution with pH of 2.5 by using a microinjection pump at the speed of 6 mL/h, continuously stirring 12 h, and dialyzing to remove unbound small molecular polymer to obtain the gamma-polyglutamic acid/chitosan carrier with negative charges on the surface; then 5mL of 2 g/L aqueous solution of tea polyphenol is injected into a gamma-polyglutamic acid/chitosan carrier according to the speed of 10 mL/h, stirred overnight and transferred into a dialysis bag, 10 mmol/L of citric acid buffer solution with the pH of 2.5 is used for dialysis to remove unbound free drug molecules, the buffer solution is replaced by 1 h at intervals until no ultraviolet absorption of tea polyphenol is detected in the solution outside the dialysis bag, the solution in the dialysis bag is dried for 15 h under the conditions of the vacuum degree of more than 0.1 mmHg and the temperature of minus 30 ℃, and then the solution is dried for 8 h under the conditions of the vacuum degree of more than 0.1 mmHg and the temperature of 10 ℃ to obtain TP-NPs for later use.
(2) The gastrostomy tube coating section was ultrasonically cleaned with methanol and deionized water, respectively, 5min, at an ultrasonic frequency of 20: 20kHz, and then blown to a surface dry state, about 3: 3 min, by a nitrogen dry blowing instrument.
(3) Immersing the dried gastrostomy tube coating section into a benzophenone/ethanol solution containing 10wt.% for 2 min, taking out, washing in methanol solution for 3 times uniformly, and blowing to the surface dry state by a nitrogen dry blowing instrument.
(4) 1G TP powder, 1g TP-NPs and 0.75 g ascorbic acid are weighed and fully dissolved in 74 ml purified water, then 23 g hydrogel monomer acrylamide, 0.05 g cross-linking agent N, N-methylene bisacrylamide and 0.2 g photoinitiator Irgacure2959 are sequentially added, after the complete dissolution, gel pre-solution is prepared, and the gel pre-solution is subjected to ultrasonic degassing under the conditions of 43 kHz and 5kPa for 20 min.
(5) Immersing the gastrostomy tube coating section treated in the steps (2) and (3) into the gel pre-solution fully, taking out, and then adopting UVP CL-1000 to irradiate, setting the wavelength to 365 nm, the power to 30W and the duration to 30min, thereby forming a first TP-gel coating layer.
(6) The TP-gel coating was rinsed thoroughly with buffer at about 20 min to remove uncrosslinked gel polymer solution.
(7) Repeating the operations of the steps (5) and (6) until 2 layers of TP-gel coating are formed, and then the tea polyphenol bionic coating is prepared.
Example 3
The preparation method comprises the following specific steps of:
(1) Preparation of TP-NPs: at room temperature and stirring speed of 600 r/min, dropwise adding 10 mL of 2 g/L gamma-polyglutamic acid into 50mL of 1.0 g/L chitosan acetic acid buffer solution with pH of 2.5 by using a microinjection pump at the speed of 6 mL/h, continuously stirring 12 h, and dialyzing to remove unbound small molecular polymer to obtain the gamma-polyglutamic acid/chitosan carrier with negative charges on the surface; then 5mL of 2 g/L aqueous solution of tea polyphenol is injected into a gamma-polyglutamic acid/chitosan carrier according to the speed of 10 mL/h, stirred overnight and transferred into a dialysis bag, 10 mmol/L of citric acid buffer solution with the pH of 2.5 is used for dialysis to remove unbound free drug molecules, the buffer solution is replaced by 1 h at intervals until no ultraviolet absorption of tea polyphenol is detected in the solution outside the dialysis bag, the solution in the dialysis bag is dried for 15 h under the conditions of the vacuum degree of more than 0.1 mmHg and the temperature of minus 30 ℃, and then the solution is dried for 8 h under the conditions of the vacuum degree of more than 0.1 mmHg and the temperature of 10 ℃ to obtain TP-NPs for later use.
(2) The gastrostomy tube coating section was ultrasonically cleaned with methanol and deionized water, respectively, 15 min, at an ultrasonic frequency of 60: 60 kHz, and then blown to a surface dry state, about 3: 3 min, by a nitrogen dry blowing instrument.
(3) Immersing the dried gastrostomy tube coating section into a benzophenone/ethanol solution containing 30wt.% for 2 min, taking out, washing in methanol solution for 3 times uniformly, and blowing to the surface dry state by a nitrogen dry blowing instrument.
(4) 1G TP powder, 1g TP-NPs and 0.75 g ascorbic acid are weighed and fully dissolved in 74 ml purified water, then 23 g hydrogel monomer acrylamide, 0.05 g cross-linking agent N, N-methylene bisacrylamide and 0.2 g photoinitiator Irgacure2959 are sequentially added, after the complete dissolution, gel pre-solution is prepared, and the gel pre-solution is subjected to ultrasonic degassing under the conditions of 43 kHz and 5kPa for 20 min.
(5) Immersing the gastrostomy tube coating section treated in the steps (2) and (3) into the gel pre-solution fully, taking out, and then adopting UVP CL-1000 to irradiate, setting the wavelength to 365 nm, the power to 30W and the duration to 90 min, so as to form a first TP-gel coating layer.
(6) The TP-gel coating was rinsed thoroughly with buffer at about 40 min to remove the uncrosslinked hydrogel polymer solution.
(7) Repeating the operations of the steps (5) and (6) until 8 layers of TP-gel coating are formed, and then the tea polyphenol bionic coating is prepared.
Example 4
The other points are the same as in example 1, except that: and (3) adding TP powder in the gel pre-solution in the step (4) to be 0.5 g, TP-NPs to be 0.5 g and ascorbic acid to be 0.5 g, and then obtaining purified water to be 75.25 ml.
Example 5
The other points are the same as in example 1, except that: and (3) adding TP powder in the gel pre-solution in the step (4) to 1.5 g, adding TP-NPs to 1.5 g and adding ascorbic acid to 1g, wherein purified water is 72.75 ml.
Example 6
The other points are the same as in example 1, except that: the gel pre-solution degassing method in the step (4) is a vacuum degassing method, the gel pre-solution is placed in a vacuum suction filter, the pressure is reduced to 0.07 kPa, and the vacuum filtration is carried out at normal temperature for 30 min.
Example 7
The other points are the same as in example 1, except that: the gel pre-solution degassing method in the step (4) is a helium-blown degassing method, and helium is introduced into a liquid storage container of the gel pre-solution at a flow rate of about 60 mL/min under the pressure of 0.1 MPa ℃ for 15 min.
Comparative example 1
Other conditions were the same as in example 1 except that TP powder, TP-NPs and ascorbic acid were not added in step (4), specifically the steps of: taking 76.75 ml of purified water, sequentially adding 23 g of hydrogel monomer acrylamide, 0.05 g of cross-linking agent N, N-methylene bisacrylamide and 0.2 g of photoinitiator Irgacure2959, preparing a gel pre-solution after complete dissolution, carrying out ultrasonic degassing on the gel pre-solution under the conditions of 43 kHz and 5 kPa for 20min, and preparing the gel coating through the subsequent steps.
Comparative example 2
Other conditions were identical to example 1, except that no TP-NPs were added in step (4), the specific steps were: fully dissolving 1g TP powder and 0.75 g ascorbic acid in 75 ml purified water, sequentially adding 23 g hydrogel monomer acrylamide, 0.05 g cross-linking agent N, N-methylene bisacrylamide and 0.2 g photoinitiator Irgacure2959, preparing a gel pre-solution after the complete dissolution, carrying out ultrasonic degassing on the gel pre-solution under the conditions of 43 kHz and 5 kPa for 20 min, and preparing the TP powder/ascorbic acid-gel coating through the subsequent steps.
Comparative example 3
Other conditions were the same as in example 1 except that no TP powder was added in step (4), the specific steps were: fully dissolving 1 g TP-NPs and 0.75 g ascorbic acid in 75 ml purified water, sequentially adding 23 g hydrogel monomer acrylamide, 0.05 g cross-linking agent N, N-methylene bisacrylamide and 0.2 g photoinitiator Irgacure2959, preparing a gel pre-solution after the complete dissolution, carrying out ultrasonic degassing on the gel pre-solution under the conditions of 43 kHz and 5 kPa for 20 min, and preparing the TP-NPs/ascorbic acid-gel coating through the subsequent steps.
Comparative example 4
Other conditions were the same as in example 1 except that no ascorbic acid was added in step (4), the specific steps were: fully dissolving 1 g TP powder and 1 g TP-NPs in 74.75 ml purified water, sequentially adding 23 g hydrogel monomer acrylamide, 0.05 g cross-linking agent N, N-methylene bisacrylamide and 0.2 g photoinitiator Irgacure2959, preparing a gel pre-solution after the complete dissolution, carrying out ultrasonic degassing on the gel pre-solution under the conditions of 43 kHz and 5 kPa for 20 min, and preparing the TP powder/TP-NPs-gel coating through the subsequent steps.
Comparative example 5
The other steps were the same as in example 1, except that: in the step (3), the coating section of the gastrostomy tube is not soaked by benzophenone/ethanol solution, and the specific steps are as follows: the gastrostomy tube coating section is subjected to ultrasonic cleaning by isopropanol and deionized water respectively for 15min, the ultrasonic frequency is set to be 60 kHz, then the surface is blown to a dry state by a nitrogen dry blowing instrument for about 3 minutes, the surface is uniformly washed in methanol solution for 3 times after being taken out, and the surface is blown to a dry state by the nitrogen dry blowing instrument again.
Comparative example 6
Other conditions were identical to example 1 except that the TP-gel coating was not rinsed with buffer in step (6) by: immersing the gastrostomy tube coating section into the gel pre-solution fully, taking out, irradiating with UVP CL-1000, setting the wavelength to 365 nm, the power to 30W and the duration to 90 min, forming a first layer TP-gel coating, repeating the operation for 5 times until 5 layers TP-gel coatings are formed, and obtaining the tea polyphenol bionic coating.
Comparative example 7
Other conditions were identical to example 1, except that the ultrasonic degassing conditions of the gel pre-solution in step (4) were set as follows: 10 Ultrasonic degassing is carried out under the conditions of kHz and 1 kPa for 2 min.
Analysis of binding force Strength
The coating binding force indicates the mutual adhesion capability between the coating and the surface of the silicone gastrostomy tube, i.e. the difficulty of peeling the coating from the surface of the gastrostomy tube, and is an important index for evaluating the performance of the coating, since it directly affects the life and the service properties (such as antibacterial, acid-resistant properties, etc.) of the coating. The bonding strength of the coatings of examples 1-7 and comparative examples 1-7 was measured according to ASTM D3359 standard frame-tape stripping, and the results are shown in Table 1, in which the addition of TP powder and TP-NPs did not affect the bonding strength of the coating.
Drug release profile
Fig. 2 is a graph showing cumulative percent release of TP in example 1, comparative example 2, comparative example 3 and comparative example 4, and no problem of abrupt release of TP in the present invention occurs by detecting the amount of TP released in the coating layer. The TP-NPs/ascorbic acid-gel coating is TP added in the form of nano particles, a small amount of release (about 25%) occurs in 60d, and about 75% of TP-NPs are still wrapped in the coating presumably related to partial nano particle breakage, so that the TP-NPs can play a continuous (more than or equal to 135 d) corrosion-resistant role; TP powder/ascorbic acid-gel coating is TP added in powder form, presents a uniform slow-release state and plays an anti-infection role in 135 d; the TP powder/TP-NPs-gel coating has a small amount of TP released in 30-45 d, which is presumably related to the degradation of TP components caused by the lack of added ascorbic acid; the TP gel coat released about 55% of the TP at 135 d.
Analysis of antibacterial Properties
The antibacterial performance of the coatings of example 1, comparative example 2 and comparative example 3 is evaluated by taking escherichia coli (E.coli) and staphylococcus aureus (S.aureus) as representative bacteria, and the antibacterial experimental results are shown in figure 3, and TP added in a powdery form has a certain inhibition effect on the E.coli and the S.aureus in the slow release process, so that the antibacterial effect on the E.coli is better, and the inhibition rate is more than 45%.
Analysis of Corrosion resistance
The main component of gastric acid is hydrochloric acid, which is monobasic strong acid and has reducibility and strong corrosiveness. In this experiment, the gastrostomy tube materials in examples 1-7 and comparative examples 1-7 were immersed in 8 mol/L of 30 mL hydrochloric acid in sequence for 12 h, the appearance is shown in Table 2, and the results show that the addition of TP-NPs in the gastrostomy tube coating has a certain corrosion resistance.
Biocompatibility analysis
The cytotoxicity test of the gastrostomy tube of comparative example 1 and example 1 by the MTT method shows that the cell viability of the gel coating and the tea polyphenol biomimetic coating gastrostomy tube material is above 78% when the cell viability is 1 d, 2d and 3d, which shows that TP has good biocompatibility.
In conclusion, the bionic coating of the tea polyphenol gastrostomy tube provided by the invention has the advantages that TP and ascorbic acid resistant to TP degradation are added into gel, a multi-layer combined acid-resistant and antibacterial barrier is formed on the surface of the gastrostomy tube, the gastrostomy tube can be prevented from being corroded by gastric acid, bacterial adhesion on the surface of the gastrostomy tube is effectively reduced, the taste and dyeing risk of the gastrostomy tube are reduced, the service life of the gastrostomy tube is prolonged, the biosafety of the gastrostomy tube is improved, and the application prospect is good.
TABLE 1 results of binding force Strength experiments
Grouping Drop-off condition Bond strength grade
Example 1 No obvious falling off 5
Example 2 No obvious falling off 5
Example 3 No obvious falling off 5
Example 4 No obvious falling off 5
Example 5 No obvious falling off 5
Example 6 No obvious falling off 5
Example 7 No obvious falling off 5
Comparative example 1 No obvious falling off 5
Comparative example 2 No obvious falling off 5
Comparative example 3 No obvious falling off 5
Comparative example 4 No obvious falling off 5
Comparative example 5 The falling area is 35 to 45 percent 1
Comparative example 6 The falling area is 5% -10% 3
Comparative example 7 The falling area is less than 5 percent 4
TABLE 2 Corrosion resistance test results
Grouping Corrosion resistance
Example 1 12 H has no change
Example 2 12 H has no change
Example 3 12 H has no change
Example 4 12 H has no change
Example 5 12 H has no change
Example 6 12 H has no change
Example 7 12 H has no change
Comparative example 1 With microcracks
Comparative example 2 12 H has no change
Comparative example 3 12 H has no change
Comparative example 4 12 H has no change
Comparative example 5 With microcracks
Comparative example 6 With microcracks
Comparative example 7 12 H has no change

Claims (10)

1. The preparation method of the tea polyphenol bionic gastrostomy tube coating is characterized by comprising the following steps of:
(1) Firstly, ultrasonically cleaning the surface of a gastrostomy tube coating section by using methanol and deionized water, then drying under nitrogen flow, soaking the surface of the gastrostomy tube coating section in a 10-30wt.% benzophenone/ethanol solution for 2min after treatment, washing the surface of the gastrostomy tube coating section by using methanol for 3 times, and drying the surface of the gastrostomy tube coating section under nitrogen flow again;
(2) Immersing the gastrostomy tube coating section in a degassed gel pre-solution consisting of 0.5-1.5wt.% tea polyphenol powder, 0.5-1.5wt.% tea polyphenol nanoparticles, 0.5-1wt.% ascorbic acid, 23wt.% hydrogel monomer, 0.05wt.% cross-linking agent and 0.2wt.% photoinitiator;
(3) Forming a tea polyphenol-gel coating by ultraviolet irradiation;
(4) Flushing the surface of the gastrostomy tube with a buffer solution to remove the uncrosslinked hydrogel monomer and the ungrafted polymer;
(5) Repeating the step (2), the step (3) and the step (4), and laminating and assembling the TP-gel coating until the number of layers reaches the required number, and marking the number as n, thereby obtaining the tea polyphenol bionic coating.
2. The method for preparing the tea polyphenol biomimetic gastrostomy tube coating according to claim 1, wherein the ultrasonic cleaning condition in the step (1) is frequency 20-60 kHz and duration 5-15 min.
3. The method for preparing a tea polyphenol biomimetic gastrostomy tube coating according to claim 1, wherein the degassing method in the step (2) is one of ultrasonic degassing, vacuum degassing and helium blowing degassing.
4. The method for preparing the tea polyphenol biomimetic gastrostomy tube coating according to claim 1, wherein the hydrogel monomer in the step (2) is acrylamide, the cross-linking agent is N, N-methylene bisacrylamide, and the photoinitiator is Irgacure2959.
5. The method for preparing the tea polyphenol biomimetic gastrostomy tube coating according to claim 1, wherein the preparation method of the tea polyphenol nano-particles in the step (2) is as follows: at room temperature and stirring speed of 600 r/min, dropwise adding 10mL of 2 g/L gamma-polyglutamic acid into 50 mL of 1 g/L chitosan-acetic acid buffer solution with pH of 2.5 by using a microinjection pump at the speed of 6 mL/h, continuously stirring 12 h, and dialyzing to remove unbound small molecular polymer to obtain the gamma-polyglutamic acid/chitosan carrier with negative charges on the surface; then 5mL of 2 g/L aqueous solution of tea polyphenol is injected into the gamma-polyglutamic acid/chitosan carrier according to the speed of 10 mL/h, the mixture is transferred into a dialysis bag after being stirred for overnight, the solution is dialyzed by 10 mmol/L citric acid buffer solution with the pH of 2.5 to remove unbound free drug molecules, the buffer solution is replaced at intervals of 1 h until the ultraviolet absorption of the tea polyphenol is not detected in the solution outside the dialysis bag, and the solution in the dialysis bag is freeze-dried to obtain tea polyphenol nano particles with the particle size of 200-300 nm.
6. The method for preparing the tea polyphenol bionic gastrostomy tube coating according to claim 1, wherein the ultraviolet irradiation in the step (3) is set to 365 nm, the power is 30W, and the duration is 30-90 min.
7. The method for preparing the tea polyphenol biomimetic gastrostomy tube coating according to claim 1, wherein the time period for flushing the surface of the gastrostomy tube with the buffer solution in the step (4) is 20-40 min.
8. The method for preparing the tea polyphenol bionic gastrostomy tube coating according to claim 1, wherein the number n of the layers in the step (5) is 2-8, and the thickness of each layer is 10-15 mu m.
9. The method for preparing the tea polyphenol bionic gastrostomy tube coating according to claim 1, wherein the gastrostomy tube is made of silicone rubber.
10. A tea polyphenol biomimetic gastrostomy tube coating, characterized in that it is prepared according to the preparation method of any one of claims 1-9.
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1913962A1 (en) * 2006-10-22 2008-04-23 Ophir Perelson Expandable medical device for the treatment and prevention of cardiovascular diseases
CN105331304A (en) * 2014-07-24 2016-02-17 3M创新有限公司 Antibacterial adhesive composition, antibacterial non-woven fabric, cleaning product and manufacturing method of antibacterial non-woven fabric
CN116139073A (en) * 2023-01-17 2023-05-23 山西医科大学 Inflammation targeting hydrogel loaded with antioxidant nano particles and preparation method thereof
CN117045607A (en) * 2023-07-13 2023-11-14 广东医科大学 Preparation method and application of bionic tea polyphenol nano-particles
CN117357713A (en) * 2023-09-18 2024-01-09 浙江大学 Preparation method of microenvironment self-response anticoagulation anti-inflammatory self-growth coating for cardiovascular implantation interventional instrument

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1913962A1 (en) * 2006-10-22 2008-04-23 Ophir Perelson Expandable medical device for the treatment and prevention of cardiovascular diseases
CN105331304A (en) * 2014-07-24 2016-02-17 3M创新有限公司 Antibacterial adhesive composition, antibacterial non-woven fabric, cleaning product and manufacturing method of antibacterial non-woven fabric
CN116139073A (en) * 2023-01-17 2023-05-23 山西医科大学 Inflammation targeting hydrogel loaded with antioxidant nano particles and preparation method thereof
CN117045607A (en) * 2023-07-13 2023-11-14 广东医科大学 Preparation method and application of bionic tea polyphenol nano-particles
CN117357713A (en) * 2023-09-18 2024-01-09 浙江大学 Preparation method of microenvironment self-response anticoagulation anti-inflammatory self-growth coating for cardiovascular implantation interventional instrument

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