Venous catheter and preparation method thereof

Abstract

The invention discloses a venous catheter and a preparation method thereof. The antibacterial nano-metal particles are used for improving the antibacterial property of a polyurethane heparinized coating in the prior art, the copper nano-metal particles, the silver nano-metal particles and the zinc nano-metal particles are selected as antibacterial agents, copper and silver can endow the coating with the good antibacterial property, but the coating is not friendly to the biocompatibility of materials, and therefore the antibacterial property of the polyurethane heparinized coating is improved. And a small amount of zinc can improve the antibacterial property of the material and maintain good biocompatibility at the same time, so that the material meets the use requirements of medical materials.

Description

Technical Field

[0001] The invention relates to the field of medical coatings, and in particular to a venous catheter and a preparation method thereof. Background Art

[0002] Intravenous catheterization is a commonly used treatment method in clinical work. Inpatients need to receive infusions every day. In order to reduce the pain caused by daily venous puncture, an indwelling needle can be implanted in the vein to avoid multiple punctures per day, thereby ensuring smooth intravenous infusion.

[0003] Intravenous catheters are important medical devices in intravenous catheterization therapy. As a medical material, they must have high requirements for antibacterial properties and biocompatibility. Chinese patent CN201310704230.1 uses polyurethane heparinized coating liquid to improve the biocompatibility of medical materials. However, quaternary ammonium salts need to be added to improve the antibacterial properties of the material, which will cause the biocompatibility of the material to deteriorate. In view of this, the present invention hopes to design an intravenous catheter with excellent antibacterial properties and good biocompatibility. Summary of the invention

[0004] In view of the problems existing in the prior art, the object of the present invention is to provide a method for preparing a venous catheter, wherein the venous catheter prepared by the method has excellent antibacterial properties and good biocompatibility.

[0005] A method for preparing a venous catheter, the method comprising the following steps:

[0006] Pretreatment of intravenous catheter: Take polyurethane intravenous catheter as the substrate, clean it with ethanol and deionized water for 30-60 minutes respectively under ultrasonic assistance, and dry it under nitrogen for later use;

[0007] Prepare the coating solution: first add 5-8 parts of polycarbonate diol and 1.1-1.208 parts of polyethylene glycol into a reaction container, evacuate and heat to 75-80°C for dehydration for 2-2.5h, then add 1.9-2.18 parts of lysine diisocyanate and 0.03-0.05 parts of stannous octoate, and prepolymerize at 75-80°C for 1-1.2h to obtain a prepolymer; dissolve 0.76-0.85 parts of 2,2-dihydroxymethylpropionic acid in 37-40 parts of water, then add the above prepolymer under high-speed stirring, and then add NaOH solution The pH of the emulsion is adjusted to 7.0-7.2 to obtain an aqueous non-toxic polyurethane emulsion with a solid content of 25-27%. Heparin sodium with a weight average molecular weight of about 9000-12000 is prepared into a solution with a concentration of 9-10.5 g / L, and then mixed with the aqueous non-toxic polyurethane emulsion in the same volume under stirring, and finally nano-metal zinc is added and stirred to obtain a polyurethane heparinized antibacterial coating liquid, wherein the mass ratio of heparin sodium to polyurethane is 4-4.5%, and the mass ratio of nano-metal zinc to polyurethane is 1.2-3.6%.

[0008] Preparation of coating: A layer of polyurethane heparinized antibacterial coating was prepared on the surface of the polyurethane intravenous catheter by the dipping method.

[0009] Preferably, the cleaning time is 30 minutes.

[0010] Preferably, the molecular weight is 12,000.

[0011] Preferably, the mass ratio of the nano metal zinc to the polyurethane is 2.3%.

[0012] Preferably, the pH is 7.2.

[0013] Furthermore, the present invention also provides a venous catheter, which is prepared by the above method.

[0014] The present invention utilizes antibacterial nano-metal particles to improve the antibacterial property of the polyurethane heparinized coating in the prior art. We have selected three nano-metal particles of copper, silver and zinc as antibacterial agents. Among them, although copper and silver can give the coating better antibacterial properties, they are not friendly to the biocompatibility of the material. A small amount of zinc can improve the antibacterial properties of the material while maintaining good biocompatibility, so that it can meet the use requirements of medical materials. DETAILED DESCRIPTION

[0015] The technical effects of the present invention are verified below through specific examples, but the embodiments of the present invention are not limited thereto.

[0016] Example 1

[0017] Pretreatment of intravenous catheter: Take polyurethane intravenous catheter as the substrate, clean it with ethanol and deionized water for 30 minutes respectively under ultrasonic assistance, and dry it under nitrogen for later use;

[0018] Preparation of coating solution: first, 5 parts of polycarbonate diol and 1.208 parts of polyethylene glycol are added to a reaction container, vacuumed and heated to 80°C for dehydration for 2 hours, then 2.18 parts of lysine diisocyanate and 0.03 parts of stannous octoate are added, and prepolymerization reaction is carried out at 75°C for 1 hour to obtain a prepolymer; 0.76 parts of 2,2-dihydroxymethyl propionic acid are dissolved in 37 parts of water, and then the prepolymer is added under high-speed stirring, and then NaOH solution is added to adjust the pH of the emulsion to 7.2 to obtain an aqueous non-toxic polyurethane emulsion with a solid content of 25%; sodium heparin with a weight-average molecular weight of about 12,000 is prepared into a solution with a concentration of 9 g / L, and then, under stirring, the same volume is mixed evenly with the aqueous non-toxic polyurethane emulsion, and finally nano-metal zinc is added and stirred evenly to obtain a polyurethane heparinized antibacterial coating suspension, wherein the mass ratio of sodium heparin to polyurethane is 4%, and the mass ratio of nano-metal zinc to polyurethane is 1.2%;

[0019] Preparation of coating: A layer of polyurethane heparinized antibacterial coating was prepared on the surface of the polyurethane intravenous catheter by the dipping method.

[0020] Example 2

[0021] Pretreatment of intravenous catheter: Take polyurethane intravenous catheter as the substrate, clean it with ethanol and deionized water for 30 minutes respectively under ultrasonic assistance, and dry it under nitrogen for later use;

[0022] Preparation of coating solution: first, 5 parts of polycarbonate diol and 1.208 parts of polyethylene glycol are added to a reaction container, vacuumed and heated to 80°C for dehydration for 2 hours, then 2.18 parts of lysine diisocyanate and 0.03 parts of stannous octoate are added, and prepolymerization reaction is carried out at 75°C for 1 hour to obtain a prepolymer; 0.76 parts of 2,2-dihydroxymethyl propionic acid are dissolved in 37 parts of water, and then the prepolymer is added under high-speed stirring, and then a NaOH solution is added to adjust the pH of the emulsion to 7.2 to obtain an aqueous non-toxic polyurethane emulsion with a solid content of 25%; sodium heparin with a weight-average molecular weight of about 12,000 is prepared into a solution with a concentration of 9 g / L, and then the solution is uniformly mixed with the aqueous non-toxic polyurethane emulsion in the same volume under stirring, and finally nano-metal zinc is added and stirred to obtain a polyurethane heparinized antibacterial coating suspension, wherein the mass ratio of sodium heparin to polyurethane is 4%, and the mass ratio of nano-metal zinc to polyurethane is 2.3%;

[0023] Preparation of coating: A layer of polyurethane heparinized antibacterial coating was prepared on the surface of the polyurethane intravenous catheter by the dipping method.

[0024] Example 3

[0025] Pretreatment of intravenous catheter: Take polyurethane intravenous catheter as the substrate, clean it with ethanol and deionized water for 30 minutes respectively under ultrasonic assistance, and dry it under nitrogen for later use;

[0026] Preparation of coating solution: first, 5 parts of polycarbonate diol and 1.208 parts of polyethylene glycol are added to a reaction container, vacuumed and heated to 80°C for dehydration for 2 hours, then 2.18 parts of lysine diisocyanate and 0.03 parts of stannous octoate are added, and prepolymerization reaction is carried out at 75°C for 1 hour to obtain a prepolymer; 0.76 parts of 2,2-dihydroxymethyl propionic acid are dissolved in 37 parts of water, and then the prepolymer is added under high-speed stirring, and then NaOH solution is added to adjust the pH of the emulsion to 7.2 to obtain an aqueous non-toxic polyurethane emulsion with a solid content of 25%; sodium heparin with a weight-average molecular weight of about 12,000 is prepared into a solution with a concentration of 9 g / L, and then, under stirring, the same volume is mixed evenly with the aqueous non-toxic polyurethane emulsion, and finally nano-metal zinc is added and stirred evenly to obtain a polyurethane heparinized antibacterial coating suspension, wherein the mass ratio of sodium heparin to polyurethane is 4%, and the mass ratio of nano-metal zinc to polyurethane is 3.6%;

[0027] Preparation of coating: A layer of polyurethane heparinized antibacterial coating was prepared on the surface of the polyurethane intravenous catheter by the dipping method.

[0028] Comparative Example 1

[0029] Pretreatment of intravenous catheter: Take polyurethane intravenous catheter as the substrate, clean it with ethanol and deionized water for 30 minutes respectively under ultrasonic assistance, and dry it under nitrogen for later use;

[0030] Preparation of coating solution: first, 5 parts of polycarbonate diol and 1.208 parts of polyethylene glycol are added to a reaction container, vacuumed and heated to 80°C for dehydration for 2 hours, then 2.18 parts of lysine diisocyanate and 0.03 parts of stannous octoate are added, and prepolymerization reaction is carried out at 75°C for 1 hour to obtain a prepolymer; 0.76 parts of 2,2-dihydroxymethylpropionic acid are dissolved in 37 parts of water, and then the prepolymer is added under high-speed stirring, and then a NaOH solution is added to adjust the pH of the emulsion to 7.2 to obtain an aqueous non-toxic polyurethane emulsion with a solid content of 25%; sodium heparin with a weight-average molecular weight of about 12,000 is prepared into a solution with a concentration of 9 g / L, and then the solution is uniformly mixed with the aqueous non-toxic polyurethane emulsion in the same volume under stirring, and finally nano-metal silver is added and stirred to obtain a polyurethane heparinized antibacterial coating suspension, wherein the mass ratio of sodium heparin to polyurethane is 4%, and the mass ratio of nano-metal silver to polyurethane is 2.3%;

[0031] Preparation of coating: A layer of polyurethane heparinized antibacterial coating was prepared on the surface of the polyurethane intravenous catheter by the dipping method.

[0032] Comparative Example 2

[0033] Pretreatment of intravenous catheter: Take polyurethane intravenous catheter as the substrate, clean it with ethanol and deionized water for 30 minutes respectively under ultrasonic assistance, and dry it under nitrogen for later use;

[0034] Preparation of coating solution: first, 5 parts of polycarbonate diol and 1.208 parts of polyethylene glycol are added to a reaction container, vacuumed and heated to 80°C for dehydration for 2 hours, then 2.18 parts of lysine diisocyanate and 0.03 parts of stannous octoate are added, and prepolymerization reaction is carried out at 75°C for 1 hour to obtain a prepolymer; 0.76 parts of 2,2-dihydroxymethylpropionic acid are dissolved in 37 parts of water, and then the prepolymer is added under high-speed stirring, and then a NaOH solution is added to adjust the pH of the emulsion to 7.2 to obtain an aqueous non-toxic polyurethane emulsion with a solid content of 25%; sodium heparin with a weight-average molecular weight of about 12,000 is prepared into a solution with a concentration of 9 g / L, and then the solution is uniformly mixed with the aqueous non-toxic polyurethane emulsion in the same volume under stirring, and finally nano-metal copper is added and stirred to obtain a polyurethane heparinized antibacterial coating suspension, wherein the mass ratio of sodium heparin to polyurethane is 4%, and the mass ratio of nano-metal copper to polyurethane is 2.3%;

[0035] Preparation of coating: A layer of polyurethane heparinized antibacterial coating was prepared on the surface of the polyurethane intravenous catheter by the dipping method.

[0036] Comparative Example 3

[0037] Pretreatment of intravenous catheter: Take polyurethane intravenous catheter as the substrate, clean it with ethanol and deionized water for 30 minutes respectively under ultrasonic assistance, and dry it under nitrogen for later use;

[0038] Preparation of coating solution: first, 5 parts of polycarbonate diol and 1.208 parts of polyethylene glycol are added to a reaction container, vacuumed and heated to 80°C for dehydration for 2 hours, then 2.18 parts of lysine diisocyanate and 0.03 parts of stannous octoate are added, and prepolymerization reaction is carried out at 75°C for 1 hour to obtain a prepolymer; 0.76 parts of 2,2-dihydroxymethyl propionic acid are dissolved in 37 parts of water, and then the prepolymer is added under high-speed stirring, and then a NaOH solution is added to adjust the pH of the emulsion to 7.2 to obtain an aqueous non-toxic polyurethane emulsion with a solid content of 25%; sodium heparin with a weight-average molecular weight of about 12,000 is prepared into a solution with a concentration of 9 g / L, and then the solution is uniformly mixed with the aqueous non-toxic polyurethane emulsion in the same volume under stirring, and finally nano-metal zinc is added and stirred to obtain a polyurethane heparinized antibacterial coating suspension, wherein the mass ratio of sodium heparin to polyurethane is 4%, and the mass ratio of nano-metal zinc to polyurethane is 6.0%;

[0039] Preparation of coating: A layer of polyurethane heparinized antibacterial coating was prepared on the surface of the polyurethane intravenous catheter by the dipping method.

[0040] Comparative Example 4

[0041] Pretreatment of intravenous catheter: Take polyurethane intravenous catheter as the substrate, clean it with ethanol and deionized water for 30 minutes respectively under ultrasonic assistance, and dry it under nitrogen for later use;

[0042] Preparation of coating solution: first, 5 parts of polycarbonate diol and 1.208 parts of polyethylene glycol are added to a reaction container, vacuumed and heated to 80°C for dehydration for 2 hours, then 2.18 parts of lysine diisocyanate and 0.03 parts of stannous octoate are added, and prepolymerization reaction is carried out at 75°C for 1 hour to obtain a prepolymer; 0.76 parts of 2,2-dihydroxymethylpropionic acid are dissolved in 37 parts of water, and then the prepolymer is added under high-speed stirring, and then NaOH solution is added to adjust the pH of the emulsion to 7.2 to obtain an aqueous non-toxic polyurethane emulsion with a solid content of 25%; sodium heparin with a weight-average molecular weight of about 12,000 is prepared into a solution with a concentration of 9 g / L, and then the solution is uniformly mixed with the aqueous non-toxic polyurethane emulsion in the same volume under stirring to obtain a polyurethane heparinized antibacterial coating liquid, wherein the mass ratio of sodium heparin to polyurethane is 4%;

[0043] Preparation of coating: A layer of polyurethane heparinized coating was prepared on the surface of polyurethane intravenous catheter by dipping method.

[0044] Below, we evaluate the antibacterial properties and biocompatibility of the samples in Examples 1-3 and Comparative Examples 1-4 through experiments, and the evaluation method is as follows:

[0045] Antibacterial activity: The bacterial concentration was selected to be 4×10 5 cfu / ml of Staphylococcus aureus was used as the test bacterial solution. 0.2 ml of the test bacterial solution was dripped on the sample surface and cultured for 48 hours at 37°C and relative humidity RH>90%. Then the sample was taken out for live bacteria count and the antibacterial rate was obtained by counting. Five parallel tests were performed for each sample, with the blank group as the control group. The antibacterial rate calculation formula is:

[0046] R(%)=(AB) / A×100

[0047] In the formula: R represents the antibacterial rate;

[0048] A represents the average number of recovered bacteria in the control group;

[0049] B represents the average number of recovered bacteria in the examples or comparative examples.

[0050] Biocompatibility: The blood compatibility of each sample is evaluated by a hemolysis test. The principle is to put the sample in direct contact with blood and measure the amount of hemoglobin released after the red blood cell membrane is ruptured to detect the degree of hemolysis of each sample in vitro. The absorption wavelength of hemoglobin is 545nm, and its concentration can be detected by a spectrophotometer. The specific operation steps are as follows:

[0051] (1) Collect 100 mL of blood from the heart of a healthy rabbit and add 5 mL of 2% potassium oxalate to make fresh anticoagulated blood. Take 40 mL of anticoagulated blood and add 50 mL of 0.9% sodium chloride injection to dilute.

[0052] (2) Take three siliconized test tubes, add the test sample and 10 mL of sodium chloride injection into one test tube, add 10 mL of sodium chloride saline into one blank test tube as a negative control group, and add 10 mL of distilled water into the other blank test tube as a positive control group.

[0053] (3) All test tubes were kept in a 37°C water bath for 30 min, 5 mL of anticoagulated rabbit blood was added to each tube, and the tubes were kept warm at 37°C for 60 min.

[0054] (4) Take the supernatant from the test tube and measure the absorbance at a wavelength of 545 nm. Perform three parallel tests on each sample and take the average value.

[0055] The hemolysis rate was calculated as follows:

[0056] Hemolysis rate (%) = (average absorbance of sample - absorbance of negative group) / (absorbance of positive group - absorbance of negative group) × 100

[0057] The test results are shown in Table 1:

[0058] Table 1

[0059] serial number Antibacterial rate / % Hemolysis rate / % Example 1 92.3 0.37 Example 2 ＞99％ 0.21 Example 3 ＞99％ 2.36 Comparative Example 1 ＞99％ 6.21 Comparative Example 2 96.3％ 9.04 Comparative Example 3 ＞99％ 5.72 Comparative Example 4 Untested 0.46

[0060] As can be seen from Table 1, we have selected three kinds of nano-metal particles, copper, silver and zinc, as antibacterial agents. Among them, although copper and silver can give the coating better antibacterial properties, they are not friendly to the biocompatibility of the material. A small amount of zinc can improve the antibacterial properties of the material while maintaining good biocompatibility. The amount of zinc used in Examples 1 and 2 can even improve the biocompatibility of the material, so that it can meet the use requirements of medical materials.

[0061] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a venous catheter, characterized in that: The preparation method comprises the following steps: Pretreatment of intravenous catheter: Take polyurethane intravenous catheter as the substrate, clean it with ethanol and deionized water for 30-60 minutes respectively under ultrasonic assistance, and dry it under nitrogen for later use; Prepare the coating solution: first add 5-8 parts of polycarbonate diol and 1.1-1.208 parts of polyethylene glycol into a reaction container, evacuate and heat to 75-80°C for dehydration for 2-2.5h, then add 1.9-2.18 parts of lysine diisocyanate and 0.03-0.05 parts of stannous octoate, and prepolymerize at 75-80°C for 1-1.2h to obtain a prepolymer; dissolve 0.76-0.85 parts of 2,2-dihydroxymethylpropionic acid in 37-40 parts of water, then add the above prepolymer under high-speed stirring, and then add NaOH solution The pH of the emulsion is adjusted to 7.0-7.2 to obtain an aqueous non-toxic polyurethane emulsion with a solid content of 25-27%. Heparin sodium with a weight average molecular weight of about 9000-12000 is prepared into a solution with a concentration of 9-10.5 g / L, and then mixed with the aqueous non-toxic polyurethane emulsion in the same volume under stirring, and finally nano-metal zinc is added and stirred to obtain a polyurethane heparinized antibacterial coating liquid, wherein the mass ratio of heparin sodium to polyurethane is 4-4.5%, and the mass ratio of nano-metal zinc to polyurethane is 1.2-3.6%. Preparation of coating: A layer of polyurethane heparinized antibacterial coating was prepared on the surface of the polyurethane intravenous catheter by the dipping method.

2. A method for preparing a venous catheter as claimed in claim 1, characterized in that: The cleaning time is 30 minutes.

3. A method for preparing a venous catheter as claimed in claim 1, characterized in that: The weight average molecular weight is 12,000.

4. A method for preparing a venous catheter as claimed in claim 1, characterized in that: The mass ratio of the nano metal zinc to the polyurethane is 2.3%.

5. A method for preparing a venous catheter as claimed in claim 1, characterized in that: The pH was 7.

2.

6. A venous catheter, characterized in that: The intravenous catheter is prepared by the method according to any one of claims 1-5.