Low-migration high-transparency anti-adhesion medical PVC (polyvinyl chloride) paste as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of implantation medical instruments, and relates to a low-migration high-transparency anti-adhesion medical PVC (polyvinyl chloride) paste as well as a preparation method and application thereof. The low-migration high-transparency anti-adhesion medical PVC paste comprises the following main components: 100 parts of anti-adhesion PVC resin powder, 60-100 parts of a plasticizer, 1-3 parts of a stabilizer, 0.4-0.7 part of a defoaming agent and 0.1-0.4 part of a rheological additive. The preparation method comprises the following steps: firstly, uniformly mixing the plasticizer, the stabilizer and the defoaming agent to obtain a mixture A; adding anti-adhesion PVC resin powder into the mixture A, and uniformly mixing to obtain a mixture B; and finally, adding a rheological additive into the mixture B, uniformly mixing, filtering to remove impurities, and fully and uniformly mixing in vacuum, so that the preparation method is simple and easy to operate. The paste is injected into a trachea cannula provided with a spring and is heated and cured to obtain a reinforced trachea cannula, so that the catheter can be endowed with excellent anti-adhesion and antibacterial properties, and the clinical infection risk is greatly reduced; the hydrophilic property is high, and the clinical user experience is improved.

Description

Technical Field

[0001] The invention belongs to the technical field of implantable medical devices and relates to a low-migration, highly transparent, anti-adhesive medical PVC paste and a preparation method and application thereof. Background Art

[0002] Tracheal intubation refers to the technique of inserting a special endotracheal tube into the trachea through the glottis. It is a simple and effective method for establishing a patency of the airway, ventilation and oxygen supply, respiratory suction and preventing aspiration in the rescue of critically ill patients. Tracheal intubation is the most commonly used endotracheal tube. Once the patient is intubated, the endotracheal tube is left in place for no more than 72 hours for oral intubation and no more than 1 week for nasal intubation. Prolonged time is very likely to cause intubation complications.

[0003] Since the endotracheal tube currently used in clinical practice is mainly made of medical polyvinyl chloride (PVC), the tube has adhesion to airway secretions, and the airway mucosa is compressed, rubbed, and stimulated after intubation, resulting in mucosal damage. Moreover, endotracheal intubation and mechanical ventilation are prone to respiratory infection after 48 hours, namely ventilator-associated pneumonia, which has become the most common and most serious complication during mechanical ventilation, with high morbidity and mortality, poor treatment effect, and large consumption of medical resources. The common pathogens of respiratory tract infection and ventilator-associated pneumonia caused by endotracheal intubation are Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumoniae, etc., and these bacteria can appear successively or overlappingly in endotracheal intubated patients, showing multidrug resistance or even pan-drug resistance. Therefore, it is necessary to give anti-adhesion to the endotracheal tube.

[0004] The reinforced endotracheal tube is a endotracheal tube with a built-in steel wire spring that is formed by heating through a PVC paste dipping process. Because the tube body is supported by a stainless steel spring, it can withstand compression and bends, and is easy to shape, which can better open the surgical field of view. It is widely used in clinical applications. Because PVC paste contains a large amount of plasticizers, the reinforced endotracheal tube has the risk of plasticizer migration, so it is necessary to reduce the amount of plasticizer migration.

[0005] Patent document CN103948973A discloses a medical endotracheal catheter with safe and efficient antibacterial properties, with tetraethyl orthosilicate (TEOS) as a silicon source, y-methacryloxypropyl trimethoxysilane (KH570) methyltriethoxysilane (MTES) as an organic phase precursor, and inorganic nanosilver as an antibacterial agent, and a sol-gel method, and then a endotracheal tube catheter as a substrate, and a surface antibacterial coating is performed to prepare an organosilicon silver-loaded antibacterial coating endotracheal tube catheter. The organosilicon silver-loaded antibacterial coating endotracheal tube catheter of the present invention can reduce the related infection complications during the endotracheal tube indwelling process, is not suitable for reinforced endotracheal tubes, and the reinforced endotracheal tube itself is heated and cured by PVC paste. If the reinforced endotracheal tube is antibacterially modified, surface activation and reheating and curing are required. These conditions will destroy PVC and accelerate the migration of plasticizers, additives, etc.

[0006] Patent document CN104771789A discloses an antibacterial medical catheter, which is placed at 120-180°C for heat treatment for 20-60 minutes, further treated with a plasma with a power of 20-100 watts for 3-8 minutes, and then immersed in a 25-75% polyguanidine aqueous solution by mass. After immersion for 5-15 minutes, the medical catheter is pulled 1-5 times, and finally the immersed medical catheter is placed in an oven at 60-80°C for 8-16 hours. The antibacterial medical catheter prepared by the invention is easy to prepare, low in cost, and has good antibacterial properties. However, the antibacterial coating is easy to fall off, has poor stability, and takes a long time to solidify, so it is not suitable for mass production.

[0007] Patent document CN104387699A provides a medical PVC paste material and a preparation method thereof, wherein the PVC paste material comprises: PVC paste resin powder, glass microspheres, light calcium carbonate, glyceride plasticizer, potassium zinc stabilizer, dibutyl phthalate, silicone oil, silicone defoamer, histidine and lignin. The preparation method is to first add the glyceride plasticizer to a stirred tank, add glass microspheres, light calcium carbonate, potassium zinc stabilizer and dibutyl phthalate while stirring, and obtain mixture I; then add silicone oil, silicone defoamer, histidine and lignin to mixture I, stir while adding, and obtain mixture II; then add PVC paste resin powder to mixture II, stir while adding until the PVC paste resin powder is completely soaked, and then put it into ultrasonic vibration dispersion to obtain. The plasticizer used in this document has a small molecular weight, is easy to migrate, has no rheological additive, and the paste is prone to sedimentation and sagging.

[0008] In order to solve the above problems of reinforced endotracheal tubes, it is urgent to develop a PVC paste for use in reinforced endotracheal tubes that meets the performance requirements of low migration of plasticizers, high transparency of the tube body and anti-adhesion. Summary of the invention

[0009] Based on this, the purpose of the present invention is to provide a low-migration, highly transparent, anti-adhesive medical PVC paste, which is used on a reinforced endotracheal tube to give the tube excellent anti-adhesion and antibacterial properties, greatly reducing the risk of clinical infection; it has strong hydrophilicity and improves the clinical user experience.

[0010] The invention also provides a preparation method of a low-migration, highly transparent, and anti-adhesive medical PVC paste, application of the paste on a reinforced endotracheal cannula, a reinforced endotracheal cannula containing the paste, and a molding method.

[0011] To achieve the above object, the present invention adopts the following technical solutions: The invention provides a low-migration, highly transparent, anti-adhesion medical PVC paste, the main components of which include 100 parts of anti-adhesion PVC resin powder, 60-100 parts of a plasticizer, 1-3 parts of a stabilizer, 0.4-0.7 parts of a defoamer and 0.1-0.4 parts of a rheological additive; the components are measured in parts by weight.

[0012] Furthermore, the anti-adhesion PVC resin powder is prepared by first subjecting conventional PVC resin powder to an ammoniation treatment and then subjecting it to a zwitterionic anti-adhesion polymer grafting modification, wherein the conventional PVC resin powder preferably has a degree of polymerization of 1000-2000, further preferably a degree of polymerization of 1400-1800, and further preferably a model of LP010 (LG, South Korea).

[0013] Furthermore, the ammoniation treatment process includes: immersing the conventional PVC resin powder in a triethylenetetramine aqueous solution, and after mixing, filtering, washing, and drying, forming an extended chain containing multiple amino groups on the surface of the PVC resin powder. The conventional PVC resin powder is stirred and dissolved in the triethylenetetramine aqueous solution, and different addition ratios can be selected as needed. The preferred addition amount is 5-30 parts by weight of conventional PVC resin powder per 100 parts by weight of the triethylenetetramine aqueous solution.

[0014] Furthermore, the concentration of the triethylenetetramine aqueous solution is 40%-90%, and the reaction is stirred in a nitrogen atmosphere at a temperature of 50-80°C for 1-6 hours, preferably 1-2 hours. After mixing, the mixture is filtered, rinsed with purified water to remove unreacted compounds, and vacuum dried for 24±0.5 hours to form an extended chain containing multiple amino groups on the surface of the PVC powder.

[0015] Furthermore, the zwitterionic anti-adhesion polymer uses methacryloylethyl sulfobetaine and glycidyl methacrylate in a mass ratio of 10:1 to 5:5 as main raw materials.

[0016] Further, the aminated PVC resin powder is immersed in an aqueous solution of a zwitterionic anti-adhesion polymer with a concentration of 10-100 mg / mL, preferably 5-30 parts by weight of the aminated PVC resin powder is added to 100 parts by weight of the zwitterionic anti-adhesion polymer aqueous solution. The reaction is carried out in a nitrogen atmosphere at a temperature of 50-80° C. for 1-8 hours, preferably 4-6 hours, and then filtered, rinsed with purified water, and vacuum dried for 24±0.5 hours to obtain the anti-adhesion PVC resin powder.

[0017] Furthermore, the specific preparation process of the zwitterionic anti-adhesion polymer includes: taking a certain amount of methacryloylethyl sulfobetaine (DMAPS) and dissolving it in purified water, taking a certain amount of glycidyl methacrylate (GMA) and dissolving it in N,N-dimethylformamide (DMF), and adding it to the DMAPS aqueous solution under stirring, wherein the DMAPS:GMA monomer ratio is 10:1-5:5. Using ammonium persulfate with a monomer mass ratio of 2% and sodium bisulfite with a monomer mass ratio of 1% as catalysts, reacting at a temperature of 45±1°C for 3-6h, the reaction is completed, and naturally cooled to room temperature, dialyzed with distilled water for 24±0.5h to remove unreacted monomers and DMF, and freeze-dried to obtain a pure zwitterionic anti-adhesion polymer.

[0018] Furthermore, the plasticizer includes any one of dioctyl phthalate (DOP), diisooctyl cyclohexane-1,2-dicarboxylate (DEHCH), diisononyl cyclohexane-1,2-dicarboxylate (DINCH) and triisooctyl phosphite (TOTM), or any one of them is compounded with acetyl tributyl citrate (ATBC); the rheological additive is a modified polyurea compound, and the modified polyurea compound is preferably BYK-410 (BYK, Germany), ECO6500 (Aike, Germany) or Deqian 2810 (DeuRheo).

[0019] Furthermore, the defoamer includes a compound of a polyoxyalkylene derivative compound and a silicone defoamer; the polyoxyalkylene defoamer is preferably BYK-3155 (BYK, Germany), and the silicone defoamer is preferably F1075 (Zhongdimei, Dongguan, China) and AFE-1520 (Dow Corning, USA); the stabilizer is a calcium zinc stabilizer; further, the calcium zinc stabilizer is preferably LTX-630Q (KDC, South Korea) or CZ-190 (Yafeng, Taiwan, China).

[0020] The present invention also provides a method for preparing a low-migration, highly transparent, and anti-adhesive medical PVC paste. The method comprises the following steps: firstly, mixing a plasticizer, a stabilizer, and a defoamer to obtain a mixture A; then adding anti-adhesive PVC resin powder to the mixture A and mixing to obtain a mixture B; finally, adding a rheological additive to the mixture B and mixing, filtering to remove impurities, and degassing under vacuum to obtain the mixture.

[0021] Furthermore, the preparation method comprises the following steps: (1) mixing a plasticizer, a stabilizer and a defoamer, and stirring at a speed of 15-55 rpm for 5-20 minutes to obtain a mixture A; (2) adding anti-adhesion PVC resin powder to the mixture A, and continuing to stir at a speed of 15-55 rpm for 30-60 minutes to obtain a mixture B; (3) adding a rheological additive to the mixture B, and continuing to stir at a speed of 15-55 rpm for 30-60 minutes to obtain a mixture C; (4) filtering the PVC paste through a filter screen and then pumping it into a vacuum tank, and degassing under a vacuum degree of 0.01 to 0.03 MPa to obtain the mixture.

[0022] The present invention further provides an application of a low-migration, highly transparent, anti-adhesive medical PVC paste in medical device products. The medical device products are made of PVC material, including anesthesia masks, interventional catheters, anesthesia catheters, endotracheal tubes, etc. The preferred product is a reinforced endotracheal tube.

[0023] The present invention further provides a reinforced endotracheal tube, which contains the low-migration, highly transparent, anti-adhesion medical PVC paste provided by the present invention.

[0024] Finally, the present invention provides a molding method for a reinforced endotracheal tube, which comprises injecting the low-migration, highly transparent, and anti-adhesive medical PVC paste into a endotracheal tube body pre-loaded with a spring, hanging the tube body to remove excess paste, and then heating and curing to obtain a reinforced endotracheal tube with low-migration, highly transparent, and anti-adhesive properties; wherein the tube body is hung for about 1-5 minutes to naturally remove excess paste, and then cured in a 150-170° C. oven for 3-6 minutes.

[0025] The beneficial effects of the present invention are: 1. Compared with the unmodified PVC resin paste, the low migration, high transparency and anti-adhesion medical PVC paste provided by the present invention has significantly improved hydrophilicity, and the contact angle is reduced from 98.7° to 61.3°; the anti-protein adhesion is significantly improved, and the protein adhesion is reduced from 31.6μg•cm -2 Reduced to 13.2 μg•cm -2 ; and has antibacterial properties.

[0026] 2. The low migration, highly transparent and anti-adhesive medical PVC paste provided by the present invention adopts a large molecular weight and migration-resistant plasticizer, compounded with a small molecule plasticizer, which reduces the migration of the plasticizer and has a good plasticizing effect. Among them, both orthophthalic plasticizers and non-orthophthalic plasticizers are suitable for this formula, which expands the selection range of plasticizers.

[0027] 3. The low migration, highly transparent, anti-adhesive medical PVC paste provided by the present invention adopts a modified polyurea compound rheological additive, which is selectively incompatible with the paste system. Under a suitable stirring speed, fine, needle-shaped crystals are produced, and a three-dimensional network structure is formed through the bonding force between the crystals, thereby providing the system with strong thixotropy and good anti-sagging properties.

[0028] 4. The low migration, highly transparent and anti-adhesive medical PVC paste provided by the present invention adopts a compound of polyoxyalkylene and organosilicon defoamers, which has better defoaming effect and good transparency than using polyoxyalkylene or organosilicon alone. It also solves the defect that general defoamers are easy to break emulsions and become ineffective in high shear systems, has fast defoaming speed, long anti-foaming time and high efficiency.

[0029] 5. The method for preparing the low-migration, highly transparent and anti-adhesive medical PVC paste provided by the present invention comprises the following steps: firstly mixing a small amount of liquid stabilizer and defoamer with a large amount of liquid plasticizer, and then adding anti-adhesive PVC resin powder to ensure the uniformity of the stabilizer and defoamer in the solid-liquid system as well as the uniformity and stability of the performance; and finally adding a rheological additive to improve the thixotropic properties of the mixed paste system.

[0030] 6. After the low migration, highly transparent and anti-adhesive medical PVC paste provided by the present invention is applied to the reinforced endotracheal tube, the hydrophilicity of the endotracheal tube is improved, the friction resistance is reduced, the damage to the trachea is reduced, and it has the anti-adhesion function to bacterial microorganisms, avoids the formation of biofilm, and reduces bacterial infection problems. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the technical solution of the present invention, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0032] Attached Figure 1 This is a product diagram of the low migration, highly transparent, anti-adhesion medical PVC paste provided by the present invention; Attached Figure 2 This is a product diagram of the anti-adhesion PVC resin powder provided by the present invention; Attached Figure 3 The eosin-stained pictures show that the left picture shows conventional PVC resin powder, and the right picture shows anti-adhesion PVC resin powder. Attached Figure 4 The test results of antibacterial performance are shown in the figure below. The test object on the left is the sample, and the test object on the right is the tube body. Attached Figure 5 The figure is a product diagram of the enhanced endotracheal cannula obtained in the embodiments and comparative examples; Attached Figure 6 This is a list of process parameters for preparing the anti-adhesion PVC resin powder in the examples and comparative examples; Attached Figure 7 The following is a list of parameters for the preparation process of the pastes in the embodiments and comparative examples; Attached Figure 8 The following is a table of test results of paste properties in the embodiments and comparative examples. DETAILED DESCRIPTION

[0033] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the accompanying drawings. The embodiments mentioned are all implemented on the premise of the technical solutions of the present invention, and detailed implementation processes are given, but it should be stated that the protection scope of the present invention is not limited to the following embodiments.

[0034] Example 1 1. Preparation of anti-adhesion PVC resin powder (1) Amination of conventional PVC resin powder: 100 parts of conventional PVC resin were immersed in 1000 parts of a 50% triethylenetetramine aqueous solution, stirred for reaction at 60°C in a nitrogen atmosphere for 2 hours, filtered, rinsed with purified water to remove unreacted compounds, and vacuum dried for 24 hours to make the surface of the PVC powder have an extended chain containing multiple amino groups.

[0035] (2) Synthesis of zwitterionic anti-adhesion polymer: Weigh a certain amount of methacryloylethyl sulfobetaine (DMAPS) and dissolve it in purified water, weigh a certain amount of glycidyl methacrylate (GMA) and dissolve it in N,N-dimethylformamide (DMF), and add them to the DMAPS aqueous solution while stirring, wherein the DMAPS:GMA monomer ratio is 10:1. Use ammonium persulfate with a monomer mass ratio of 2% and sodium bisulfite with a monomer mass ratio of 1% as catalysts, react at 45°C for 6h, and after the reaction is completed, cool naturally to room temperature, dialyze with distilled water for 24h to remove unreacted monomers and DMF, and freeze-dry to obtain a pure anti-adhesion polymer.

[0036] (3) Surface grafting of anti-adhesion polymer: 100 parts of aminated PVC powder were immersed in 1000 parts of zwitterionic polymer with a concentration of 10 mg / mL, reacted for 5 hours at 60°C in a nitrogen atmosphere, filtered, rinsed with purified water, and vacuum dried for 24 hours to obtain anti-adhesion PVC resin powder.

[0037] 2. Preparation of low migration, highly transparent and anti-adhesive medical PVC paste (1) 64 parts of plasticizer DOP, 35 parts of ATBC, 2.2 parts of calcium zinc stabilizer LTX-630Q, 0.3 parts of polyoxyalkylene defoamer BYK-3155, and 0.3 parts of silicone defoamer AFE-1520 were stirred at 35 rpm for 10 minutes to obtain mixture A; (2) 100 parts of anti-adhesion PVC resin powder were added to mixture A, and the mixture was further stirred at 40 rpm for 60 minutes to obtain mixture B; (3) 0.23 parts of rheological additive BYK-410 were added to mixture B, and the mixture was further stirred at 20 rpm for 30 minutes to obtain mixture C; (4) Mixture C was filtered through a filter and pumped into a vacuum tank, and vacuumed for 2 hours to degas.

[0038] 3. Preparation of enhanced endotracheal tube The upper end of the endotracheal tube body equipped with a spring is hung on an aluminum strip, and the automatic grouting machine is fed at a certain speed to inject PVC paste into the endotracheal tube body; the tube body is hung for 3.5 minutes, and the excess paste is naturally removed; then it is hung on a hook at one end of a 165℃ drying oven, and the drying oven speed is adjusted to transfer it to the other end, ensuring that it stays in the oven for 3.5 minutes, and then it is removed and cooled.

[0039] Example 2 1. Preparation of anti-adhesion PVC resin powder (1) Amination of conventional PVC resin powder: 100 parts of conventional PVC resin were immersed in 1000 parts of a 50% triethylenetetramine aqueous solution, stirred for reaction at 50°C in a nitrogen atmosphere for 2 hours, and then filtered. The mixture was rinsed with purified water to remove unreacted compounds and vacuum dried for 24 hours to make the surface of the PVC powder have an extended chain containing multiple amino groups.

[0040] (2) Synthesis of zwitterionic anti-adhesion polymer: Weigh a certain amount of methacryloylethyl sulfobetaine (DMAPS) and dissolve it in purified water, weigh a certain amount of glycidyl methacrylate (GMA) and dissolve it in N,N-dimethylformamide (DMF), and add them to the DMAPS aqueous solution while stirring, wherein the DMAPS:GMA monomer ratio is 10:1. Use ammonium persulfate with a monomer mass ratio of 2% and sodium bisulfite with a monomer mass ratio of 1% as catalysts, react at 45°C for 6h, and after the reaction is completed, naturally cool to room temperature, dialyze with distilled water for 24h to remove unreacted monomers and DMF, and freeze-dry to obtain pure zwitterionic anti-adhesion polymer.

[0041] (3) Surface grafting of anti-adhesion polymer: 100 parts of aminated PVC powder were immersed in 1000 parts of zwitterionic polymer with a concentration of 50 mg / mL, reacted for 5 hours at 60°C in a nitrogen atmosphere, filtered, rinsed with purified water, and vacuum dried for 24 hours to obtain anti-adhesion PVC resin powder.

[0042] 2. Preparation of low migration, highly transparent and anti-adhesive medical PVC paste (1) 92 parts of plasticizer DOP, 2.2 parts of calcium zinc stabilizer CZ-190, 0.25 parts of polyoxyalkylene defoamer BYK-3155, and 0.3 parts of silicone defoamer AFE-1520 were stirred at 40 rpm for 8 minutes to obtain mixture A; (2) 100 parts of anti-adhesion PVC resin powder were added to mixture A, and the mixture was further stirred at 45 rpm for 55 minutes to obtain mixture B; (3) 0.18 parts of rheological additive BYK-410 were added to mixture B, and the mixture was further stirred at 20 rpm for 30 minutes to obtain mixture C; (4) Mixture C was filtered through a filter and pumped into a vacuum tank, and vacuumed for 2 hours to degas.

[0043] 3. Preparation of enhanced endotracheal tube The upper end of the endotracheal tube body equipped with a spring is hung on an aluminum strip, and the automatic grouting machine is fed at a certain speed to inject PVC paste into the endotracheal tube body; the tube body is hung for 4 minutes to naturally remove excess paste; then it is hung on a hook at one end of a 160℃ drying oven, and the drying oven speed is adjusted to transfer it to the other end, ensuring that it stays in the oven for 4 minutes, and then removed and cooled.

[0044] Example 3 1. Preparation of anti-adhesion PVC resin powder (1) Amination of conventional PVC resin powder: 100 parts of conventional PVC resin were immersed in 1000 parts of a 50% triethylenetetramine aqueous solution, stirred for reaction at 40°C in a nitrogen atmosphere for 2 hours, and then filtered. The mixture was rinsed with purified water to remove unreacted compounds and vacuum dried for 24 hours to make the surface of the PVC powder have an extended chain containing multiple amino groups.

[0045] (2) Synthesis of zwitterionic anti-adhesion polymer: Weigh a certain amount of methacryloylethyl sulfobetaine (DMAPS) and dissolve it in purified water, weigh a certain amount of glycidyl methacrylate (GMA) and dissolve it in N,N-dimethylformamide (DMF), and add them to the DMAPS aqueous solution while stirring, wherein the DMAPS:GMA monomer ratio is 10:1. Use ammonium persulfate with a monomer mass ratio of 2% and sodium bisulfite with a monomer mass ratio of 1% as catalysts, react at 45°C for 6h, and after the reaction is completed, naturally cool to room temperature, dialyze with distilled water for 24h to remove unreacted monomers and DMF, and freeze-dry to obtain pure zwitterionic anti-adhesion polymer.

[0046] (3) Surface grafting of anti-adhesion polymer: 100 parts of aminated PVC powder were immersed in 1000 parts of zwitterionic polymer with a concentration of 100 mg / mL, reacted for 5 hours at 60°C in a nitrogen atmosphere, filtered, rinsed with purified water, and vacuum dried for 24 hours to obtain anti-adhesion PVC resin powder.

[0047] 2. Preparation of low migration, highly transparent and anti-adhesive medical PVC paste (1) 60 parts of plasticizer DEHCH, 32 parts of plasticizer ATBC, 2.2 parts of calcium zinc stabilizer CZ-190, 0.3 parts of polyoxyalkylene defoamer BYK-3155, and 0.3 parts of silicone defoamer AFE-1520 were stirred at 35 rpm for 10 min to obtain mixture A; (2) 100 parts of antibacterial PVC resin powder were added to mixture A and the mixture was stirred at 40 rpm for 60 min to obtain mixture B; (3) 0.25 parts of rheological additive BYK-410 were added to mixture B and the mixture was stirred at 30 rpm for 20 min to obtain mixture C; (4) Mixture C was filtered through a filter and pumped into a vacuum tank, and evacuated for 2 hours to degas. PVC paste was obtained.

[0048] 3. Preparation of enhanced endotracheal tube The upper end of the endotracheal tube body equipped with a spring is hung on an aluminum strip, and the automatic grouting machine is fed at a certain speed to inject PVC paste into the endotracheal tube body; the tube body is hung for 3.5 minutes to naturally remove excess paste; then it is hung on a hook at one end of a 155℃ drying oven, and the drying oven speed is adjusted to transfer it to the other end, ensuring that it stays in the oven for 5 minutes, and then removed and cooled.

[0049] Example 4 1. Preparation of anti-adhesion PVC resin powder (1) Amination of conventional PVC resin powder: 100 parts of conventional PVC resin were immersed in 1000 parts of 70% triethylenetetramine aqueous solution, stirred for reaction at 50°C under nitrogen atmosphere for 1 hour, filtered, rinsed with purified water to remove unreacted compounds, and vacuum dried for 24 hours to make the surface of the PVC powder have extended chains containing multiple amino groups.

[0050] (2) Synthesis of zwitterionic anti-adhesion polymer: Weigh a certain amount of methacryloylethyl sulfobetaine (DMAPS) and dissolve it in purified water, weigh a certain amount of glycidyl methacrylate (GMA) and dissolve it in N,N-dimethylformamide (DMF), and add them to the DMAPS aqueous solution while stirring, wherein the DMAPS:GMA monomer ratio is 8:2. Use ammonium persulfate with a monomer mass ratio of 2% and sodium bisulfite with a monomer mass ratio of 1% as catalysts, react at 45°C for 5h, and after the reaction is completed, cool naturally to room temperature, dialyze with distilled water for 24h to remove unreacted monomers and DMF, and freeze-dry to obtain pure zwitterionic anti-adhesion polymer.

[0051] (3) Surface grafting of anti-adhesion polymer: 100 parts of aminated PVC powder were immersed in 1000 parts of zwitterionic polymer with a concentration of 10 mg / mL, reacted for 5 hours at 60°C in a nitrogen atmosphere, filtered, rinsed with purified water, and vacuum dried for 24 hours to obtain anti-adhesion PVC resin powder.

[0052] 2. Preparation of low migration, highly transparent and anti-adhesive medical PVC paste (1) 62 parts of plasticizer DINCH, 32 parts of ATBC, 2.2 parts of calcium zinc stabilizer LTX-630Q, 0.3 parts of polyoxyalkylene defoamer BYK-3155, and 0.3 parts of silicone defoamer AFE-1520 were stirred at 35 rpm for 10 min to obtain mixture A; (2) 100 parts of antibacterial PVC resin powder were added to mixture A and the mixture was stirred at 45 rpm for 55 min to obtain mixture B; (3) 0.24 parts of rheological additive BYK-410 were added to mixture B and the mixture was stirred at 20 rpm for 30 min to obtain mixture C; (4) Mixture C was filtered through a filter and pumped into a vacuum tank, and vacuumed for 2 hours to degas.

[0053] 3. Preparation of enhanced endotracheal tube The upper end of the endotracheal tube body equipped with a spring is hung on an aluminum strip, and the automatic grouting machine is fed at a certain speed to inject PVC paste into the endotracheal tube body; the tube body is hung for 3.5 minutes to naturally remove excess paste; then it is hung on a hook at one end of a 155℃ drying oven, and the drying oven speed is adjusted to transfer it to the other end, ensuring that it stays in the oven for 5 minutes, and then removed and cooled.

[0054] Example 5 1. Preparation of anti-adhesion PVC resin powder (1) Amination of conventional PVC resin powder: 100 parts of conventional PVC resin were immersed in 1000 parts of a 70% triethylenetetramine aqueous solution, stirred for reaction at 40°C in a nitrogen atmosphere for 1.5 hours, then filtered, rinsed with purified water to remove unreacted compounds, and vacuum dried for 24 hours to make the surface of the PVC powder have an extended chain containing multiple amino groups.

[0055] (2) Synthesis of zwitterionic anti-adhesion polymer: Weigh a certain amount of methacryloylethyl sulfobetaine (DMAPS) and dissolve it in purified water, weigh a certain amount of glycidyl methacrylate (GMA) and dissolve it in N,N-dimethylformamide (DMF), and add them to the DMAPS aqueous solution while stirring, wherein the DMAPS:GMA monomer ratio is 8:2. Use ammonium persulfate with a monomer mass ratio of 2% and sodium bisulfite with a monomer mass ratio of 1% as catalysts, react at 45°C for 5h, and after the reaction is completed, cool naturally to room temperature, dialyze with distilled water for 24h to remove unreacted monomers and DMF, and freeze-dry to obtain pure zwitterionic anti-adhesion polymer.

[0056] (3) Surface grafting of anti-adhesion polymer: 100 parts of aminated PVC powder were immersed in 1000 parts of zwitterionic polymer with a concentration of 50 mg / mL, reacted for 5 hours at 60°C in a nitrogen atmosphere, filtered, rinsed with purified water, and vacuum dried for 24 hours to obtain anti-adhesion PVC resin powder.

[0057] 2. Preparation of low migration, highly transparent and anti-adhesive medical PVC paste (1) 64 parts of plasticizer TOTM, 35 parts of ATBC, 2.2 parts of calcium zinc stabilized CZ190, 0.3 parts of F1075, and 0.3 parts of polyoxyalkylene defoamer BYK-3155 were stirred at 35 rpm for 10 min to obtain mixture A; (2) 100 parts of antibacterial PVC resin powder were added to mixture A and the mixture was stirred at 40 rpm for 60 min to obtain mixture B; (3) 0.22 parts of rheological additive ECO6500 were added to mixture B and the mixture was stirred at 20 rpm for 30 min to obtain mixture C; (4) Mixture C was filtered through a filter and pumped into a vacuum tank, and vacuumed for 2 hours to degas.

[0058] 3. Preparation of enhanced endotracheal tube The upper end of the endotracheal tube body equipped with a spring is hung on an aluminum strip, and the automatic grouting machine is fed at a certain speed to inject PVC paste into the endotracheal tube body; the tube body is hung for 3.5 minutes to naturally remove excess paste; then it is hung on a hook at one end of a 155℃ drying oven, and the drying oven speed is adjusted to transfer it to the other end, ensuring that it stays in the oven for 5 minutes, and then removed and cooled.

[0059] Example 6 1. Preparation of anti-adhesion PVC resin powder (1) Amination of conventional PVC resin powder: 100 parts of conventional PVC resin were immersed in 1000 parts of 80% triethylenetetramine aqueous solution, stirred for reaction at 50°C in a nitrogen atmosphere for 1 hour, filtered, rinsed with purified water to remove unreacted compounds, and vacuum dried for 24 hours to make the surface of the PVC powder have extended chains containing multiple amino groups.

[0060] (2) Synthesis of zwitterionic anti-adhesion polymer: Weigh a certain amount of methacryloylethyl sulfobetaine (DMAPS) and dissolve it in purified water, weigh a certain amount of glycidyl methacrylate (GMA) and dissolve it in N,N-dimethylformamide (DMF), and add them to the DMAPS aqueous solution while stirring, wherein the DMAPS:GMA monomer ratio is 8:2. Use ammonium persulfate with a monomer mass ratio of 2% and sodium bisulfite with a monomer mass ratio of 1% as catalysts, react at 45°C for 5h, and after the reaction is completed, cool naturally to room temperature, dialyze with distilled water for 24h to remove unreacted monomers and DMF, and freeze-dry to obtain pure zwitterionic anti-adhesion polymer.

[0061] (3) Surface grafting of anti-adhesion polymer: 100 parts of aminated PVC powder were immersed in 1000 parts of zwitterionic polymer with a concentration of 100 mg / mL, reacted for 5 hours at 60°C in a nitrogen atmosphere, filtered, rinsed with purified water, and vacuum dried for 24 hours to obtain anti-adhesion PVC resin powder.

[0062] 2. Preparation of low migration, highly transparent and anti-adhesive medical PVC paste (1) 92 parts of plasticizer DOP, 2.2 parts of calcium zinc stabilizer LTX-630Q, 0.3 parts of F1075, and 0.25 parts of polyoxyalkylene defoamer BYK-3155 were stirred at a speed of 35 rpm for 10 minutes to obtain mixture A; (2) 100 parts of antibacterial PVC resin powder were added to mixture A and the mixture was stirred at a speed of 40 rpm for 60 minutes to obtain mixture B; (3) 0.18 parts of rheological additive ECO6500 were added to mixture B and the mixture was stirred at a speed of 20 rpm for 30 minutes to obtain mixture C; (4) Mixture C was filtered through a filter and pumped into a vacuum tank, and vacuumed for 2 hours to degas.

[0063] 3. Preparation of enhanced endotracheal tube The upper end of the endotracheal tube body equipped with a spring is hung on an aluminum strip, and the automatic grouting machine is fed at a certain speed to inject PVC paste into the endotracheal tube body; the tube body is hung for 3.5 minutes to naturally remove excess paste; then it is hung on a hook at one end of a 155℃ drying oven, and the drying oven speed is adjusted to transfer it to the other end, ensuring that it stays in the oven for 5 minutes, and then removed and cooled.

[0064] Example 7 1. Preparation of anti-adhesion PVC resin powder (1) Amination of conventional PVC resin powder: 100 parts of conventional PVC resin were immersed in 1000 parts of 80% triethylenetetramine aqueous solution, stirred for reaction at 40°C in a nitrogen atmosphere for 1.5 hours, filtered, rinsed with purified water to remove unreacted compounds, and vacuum dried for 24 hours to make the surface of the PVC powder have extended chains containing multiple amino groups.

[0065] (2) Synthesis of zwitterionic anti-adhesion polymer: Weigh a certain amount of methacryloylethyl sulfobetaine (DMAPS) and dissolve it in purified water, weigh a certain amount of glycidyl methacrylate (GMA) and dissolve it in N,N-dimethylformamide (DMF), and add them to the DMAPS aqueous solution while stirring, wherein the DMAPS:GMA monomer ratio is 5:5. Use ammonium persulfate with a monomer mass ratio of 2% and sodium bisulfite with a monomer mass ratio of 1% as catalysts, react at 45°C for 4h, and after the reaction is completed, cool naturally to room temperature, dialyze with distilled water for 24h to remove unreacted monomers and DMF, and freeze-dry to obtain pure zwitterionic anti-adhesion polymer.

[0066] (3) Surface grafting of anti-adhesion polymer: 100 parts of aminated PVC powder were immersed in 1000 parts of zwitterionic polymer with a concentration of 50 mg / mL, reacted for 5 hours at 60°C in a nitrogen atmosphere, filtered, rinsed with purified water, and vacuum dried for 24 hours to obtain anti-adhesion PVC resin powder.

[0067] 2. Preparation of low migration, highly transparent and anti-adhesive medical PVC paste (1) 92 parts of plasticizer DOP, 2.2 parts of calcium zinc stabilizer LTX-630Q, 0.3 parts of F1075, and 0.25 parts of polyoxyalkylene defoamer BYK-3155 were stirred at a speed of 35 rpm for 10 minutes to obtain mixture A; (2) 100 parts of antibacterial PVC resin powder were added to mixture A, and the mixture was further stirred at a speed of 40 rpm for 60 minutes to obtain mixture B; (3) 0.18 parts of rheological additive Hemmingsdeqian 2810 were added to mixture B, and the mixture was further stirred at a speed of 20 rpm for 30 minutes to obtain mixture C; (4) Mixture C was filtered through a filter and pumped into a vacuum tank, and vacuumed for 2 hours to degas.

[0068] 3. Preparation of enhanced endotracheal tube The upper end of the endotracheal tube body equipped with a spring is hung on an aluminum strip, and the automatic grouting machine is fed at a certain speed to inject PVC paste into the endotracheal tube body; the tube body is hung for 3.5 minutes to naturally remove excess paste; then it is hung on a hook at one end of a 155℃ drying oven, and the drying oven speed is adjusted to transfer it to the other end, ensuring that it stays in the oven for 5 minutes, and then removed and cooled.

[0069] Comparative Example 1 The difference between Comparative Example 1 and Example 1 is that conventional PVC resin powder which has not been modified for anti-adhesion is used.

[0070] Comparative Example 2 The difference between Comparative Example 2 and Example 1 is that the plasticizer used is an equal amount of ATBC.

[0071] Comparative Example 3 The difference between Comparative Example 3 and Example 1 is that the defoaming agent used is only the organosilicon defoaming agent F1075.

[0072] Comparative Examples 4-6 The difference between Comparative Examples 4-6 and Example 1 lies in the different raw material ratios and reaction processes for preparing the anti-adhesion PVC powder.

[0073] The preparation process parameters of the PVC paste and the endotracheal tube in Examples 1-7 and Comparative Examples 1-6 are summarized in the following table: Figure 6 and Figure 7 As shown, Figure 6 List of process parameters for the preparation of anti-adhesion PVC resin powder. Figure 7 List of parameters for the paste preparation process.

[0074] Implementation effect analysis The following performance tests were performed on the pastes in Examples 1-7 and Comparative Examples 1-6. The test results are as follows: Figure 8 As shown in Table 3.

[0075] 1. Viscosity test: Turn on the rotational rheology tester and perform a self-check according to the operating steps. After the self-check is completed, set the running program. Combined with the actual use environment, set the temperature range to -10℃-40℃, add the prepared PVC paste to the sample loading table, and keep the sample at -10℃ for 90s to ensure the stability of the sample at the beginning of the test, and then start the test program. In order to compare the viscosity between different formulas horizontally, the viscosity at 25℃ is selected for each test result.

[0076] 2. Plasticizer migration test: Prepare a 50% ethanol solution for later use. Plasticize the prepared paste at 165℃ for 10min, cut it into pieces and press it into 2mm sheets at 185℃. Cut the sheet into 2cmx8cm strips, wipe the precipitate on the surface of the strips with alcohol, weigh the strips and record the mass before immersion. Use a measuring cylinder to measure 50 mL of 50% ethanol solution and place it in a centrifuge tube. Mark the centrifuge tube according to the number of the strips and place the corresponding strips in sequence. And set three parallel samples for each group of samples. Place the above centrifuge tube in a 37℃ water bath and oscillate at a constant temperature of 120 rpm for 6 hours, then ultrasonicate it in an ultrasonic cleaner for 30 minutes with an ultrasonic power of 40 khz. After the ultrasonication is completed, take out the strips and wipe the surface of the strips with alcohol, put them in a vacuum drying oven for 24 hours, weigh them, record the weight change, and characterize the plasticizer migration with the mass loss rate. The smaller the mass loss, the less the plasticizer migration.

[0077] 3. Transmittance / haze test: The paste was plasticized at 165°C for 10 minutes, cut into pieces and pressed into sheets at 185°C. The pressed sheets were tested with a transmittance tester according to the standard GB / T 2410-2008 Determination of transmittance and haze of transparent plastics. The higher the transmittance and the smaller the haze, the better the transparency of the material.

[0078] 4. Contact angle test: The prepared paste was plasticized at 165℃ for 10min, and 2*2cm thick pieces were cut from 5 points on the sample. 2 The sample was tested for water contact angle on the contact angle meter, the water drop volume was set to 8μl / time, and the average value of 5 test points was taken as the sample test result. The contact angle reflects the hydrophilicity of the material. The smaller the contact angle, the better the hydrophilicity of the material.

[0079] 5. Protein adhesion ELISA method: After washing the sample with phosphate buffer solution (PBS), put it in 100 μg / ml BSA solution and keep it at a constant temperature of 37 ℃ for 3 hours; take out the soaked sample with tweezers, and then rinse it with PBS buffer solution to wash off the BSA protein that is not adsorbed on the surface; prepare SDS detergent with a mass fraction of 0.1% with PBS buffer solution, measure a certain volume of cleaning solution with a pipette, soak the washed sample in the detergent, and ultrasonically clean it for 30 minutes; add the protein solution obtained after washing to a 96-well plate with a pipette, add Bradford reagent, put the 96-well plate into an enzyme reader, and measure the absorbance of the solution at an absorption wavelength of 595nm. Finally, the surface adsorption amount is calculated according to the standard curve, and each sample is measured 3 times to take the average value. The surface adsorption amount reflects the protein adhesion effect. The less the surface adsorption amount, the better the anti-protein adhesion effect.

[0080] 6. Quine method antibacterial performance test: The E. coli suspension was diluted to 10 7 cuf / ml as the test bacterial suspension, test sample sheet 10mm×10mm and tube body 20mm, take 6uL of the test bacterial suspension and drop it on the sample surface, place it in a 37℃ constant temperature box to dry for 4h, and then culture it with agar for 20h, and observe the results. The red color on the sample surface indicates the adhered bacteria. The test results are as follows Figure 4 As shown, 0# is the sample of comparative example 1, 1-3# are the samples of embodiment 1, the left picture is the sample (the sample preparation method is the same as the method in the contact angle test), and the right picture is the tube body. It can be seen from the figure that the sample of the comparative example has red color, indicating that bacteria are attached; the sample of embodiment 1 has no red color, indicating that no bacteria are attached, and has antibacterial properties.

[0081] 7. Friction coefficient test: The friction coefficient tester was used for testing, with a holding force of 3N, a test length of 50mm, a lifting speed of 10mm / s, and 15 cycles.

[0082] The PVC paste product is prepared by the preparation method of the low migration, high transparency and anti-adhesion medical PVC paste provided by the present invention. Figure 1 As shown, the product is milky white and viscous. The anti-adhesion PVC resin powder product (undried state) prepared by the present invention is as follows Figure 2 As shown, the anti-adhesion PVC resin powder and the conventional PVC resin powder were subjected to eosin staining experiments, and the anti-adhesion PVC resin powder was dyed red, indicating that the PVC resin powder was grafted with zwitterionic anti-adhesion polymers and had anti-adhesion properties, while the conventional PVC resin powder was not dyed because it did not have anti-adhesion properties. The dyeing results are shown in Figure 3 shown.

[0083] Combination Figure 8It can be seen from the performance test results in Table 3 that the low migration, highly transparent and anti-adhesive medical PVC paste prepared by the preparation method and component ratio provided by the present invention has the excellent properties of low plasticizer migration, good transparency, strong hydrophilicity, anti-protein adhesion and antibacterial properties. Specifically: (1) It can be seen from Comparative Example 1 and Example 1 that the conventional PVC resin powder has a large contact angle, poor hydrophilicity, high protein adhesion, poor anti-protein adhesion performance, no antibacterial performance, and a large friction coefficient. This shows that the anti-adhesion PVC resin powder in the present invention has the function of improving the hydrophilicity, anti-protein adhesion, and antibacterial performance of the product and reducing the surface friction coefficient.

[0084] (2) It can be seen from Comparative Example 2 and Example 1 that when a small molecular weight ATBC is used alone, the migration amount of the plasticizer reaches 5%, which is much higher than the average migration amount of 1% of the plasticizer in the example. This shows that the present invention uses a plasticizer with a larger molecular weight and migration resistance, or compounding with a small molecular weight plasticizer, which effectively reduces the migration of the plasticizer. Among them, both orthophthalic plasticizers and non-orthophthalic plasticizers are suitable for this formula, which expands the selection range of plasticizers.

[0085] (3) It can be seen from the comparison between Example 3 and Example 1 that the light transmittance is reduced and the haze is increased when the organosilicon defoamer F1075 is used. This indicates that the compound of the polyoxyalkylene and organosilicon defoamers provided by the present invention has a better defoaming effect than the organosilicon defoamer alone and improves the transparency.

[0086] (4) By comparing Examples 4.5.6 with Example 1, it can be seen that there are certain requirements for the preparation parameters of the anti-adhesion PVC resin powder. If it is not within the experimental parameter range, the anti-adhesion function will be affected, there will be no antibacterial effect, and the hydrophilic effect will also be poor.

[0087] After the low migration, highly transparent and anti-adhesion medical PVC paste provided by the present invention is applied to the reinforced endotracheal tube, the hydrophilicity of the endotracheal tube is improved, the friction resistance is reduced, the damage to the trachea is reduced, and the anti-adhesion function to bacterial microorganisms is possessed, biofilm formation is avoided, and bacterial infection problems are reduced. Figure 5 The figures are product pictures of reinforced endotracheal tubes prepared in the embodiments and comparative examples of the present invention, wherein ① is the sample in Embodiment 1, ④ is the sample in Comparative Example 3, and it can be seen that compared with the dark and opaque sample in Comparative Example 3, the sample in Embodiment 1 has higher transparency, indicating that the present invention selects appropriate defoaming agent and defoaming process to significantly improve the transparency of the product; ② is the appearance of the sample in Embodiment 1 after aging for 2 years, and ③ is the appearance of the sample in Comparative Example 2 after aging for 2 years, and it can be seen that compared with the transparent sample in Embodiment 1, the sample in Comparative Example 2 has reduced transparency due to the migration of the plasticizer on the inner wall, indicating that the present invention selects appropriate plasticizer to reduce the migration of the plasticizer after aging.

[0088] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A low migration, highly transparent, anti-adhesion medical PVC paste, characterized in that: The main components include 100 parts of anti-adhesion PVC resin powder, 60-100 parts of plasticizer, 1-3 parts of stabilizer, 0.4-0.7 parts of defoamer and 0.1-0.4 parts of rheological additive; the components are calculated by weight.

2. The low migration, highly transparent, anti-adhesion medical PVC paste according to claim 1, characterized in that: The anti-adhesion PVC resin powder is prepared by first subjecting conventional PVC resin powder to an ammoniation treatment and then subjecting it to a zwitterionic anti-adhesion polymer grafting modification.

3. The low migration, highly transparent, anti-adhesion medical PVC paste according to claim 2, characterized in that: The ammoniation treatment process comprises: immersing the conventional PVC resin powder in a triethylenetetramine aqueous solution, and after mixing, filtering, washing and drying, forming an extended chain containing amino groups on the surface of the conventional PVC resin powder.

4. The low migration, highly transparent, anti-adhesion medical PVC paste according to claim 2, characterized in that: The zwitterionic anti-adhesion polymer is mainly made of methacryloylethyl sulfobetaine and glycidyl methacrylate in a mass ratio of 10:1 to 5:

5.

5. The low migration, highly transparent, anti-adhesion medical PVC paste according to claim 1, characterized in that: The plasticizer comprises any one of dioctyl phthalate, diisooctyl cyclohexane-1,2-dicarboxylate, diisononyl cyclohexane-1,2-dicarboxylate and triisooctyl phosphite, or any one of them is compounded with tributyl acetyl citrate; and the rheological additive is a modified polyurea compound.

6. The low migration, highly transparent, anti-adhesion medical PVC paste according to claim 1, characterized in that: The defoaming agent comprises a compound of a polyoxyalkylene defoaming agent and a silicone defoaming agent.

7. A method for preparing the low migration, highly transparent and anti-adhesive medical PVC paste according to any one of claims 1 to 6, characterized in that: Firstly, a plasticizer, a stabilizer and a defoamer are mixed to obtain a mixture A; then, anti-adhesion PVC resin powder is added to the mixture A and mixed to obtain a mixture B; finally, a rheological additive is added to the mixture B and mixed, and then the mixture is filtered to remove impurities and degassed under vacuum to obtain the mixture.

8. Application of the low migration, highly transparent and anti-adhesive medical PVC paste according to any one of claims 1 to 6 in medical device products, characterized in that: The material of the medical device product is PVC.

9. A reinforced endotracheal tube, characterized in that: The reinforced endotracheal tube contains the low migration, highly transparent and anti-adhesive medical PVC paste described in any one of claims 1 to 6.

10. A method for forming a reinforced endotracheal tube according to claim 9, characterized in that: The low migration, high transparency and anti-adhesion medical PVC paste is injected into a tracheal cannula tube body pre-loaded with a spring, and the tube body is hung to remove excess paste, and then heated and cured to obtain a reinforced tracheal cannula with low migration, high transparency and anti-adhesion properties.

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