WO2015027752A1

WO2015027752A1 - Antibacterial medical ultrasonic coupling agent and preparation method thereof

Info

Publication number: WO2015027752A1
Application number: PCT/CN2014/081587
Authority: WO
Inventors: 李文亮; 李玉新; 孙陆果; 鲍永利; 石晶; 王春红; 石卫东
Original assignee: 长春东北师大基因工程有限公司; 东北师范大学
Priority date: 2013-08-26
Filing date: 2014-07-03
Publication date: 2015-03-05
Also published as: KR20160046907A; CN103432600A; CN103432600B; KR101990185B1

Abstract

An antibacterial medical ultrasonic coupling agent and preparation method thereof, the weight percentage of the raw materials thereof being: 1-2% polyethyleneimine quaternary ammonium salt, 1-2% polyethylene glycol, 0.05-0.1% methylene blue, and the balance being distilled water; the preparation method is: proportionally mixing various raw materials with water; then stirring the mixture while heating to dissolve and swell the raw materials; and finally removing bubbles under vacuum decompression to obtain light blue gel product.

Description

Antibacterial medical ultrasonic coupling agent and preparation method thereof

Technical field:

The invention relates to an antibacterial medical ultrasonic coupling agent, and the invention further provides a preparation method of the coupling agent, which belongs to the technical field of reagents for medical examination.

technical background:

B-ultrasound is a widely used test instrument in clinical practice. The medical ultrasonic coupling agent used in medical examination is applied to the skin of the detection site to eliminate the air between the instrument probe and the skin. Therefore, the ultrasonic coupling agent is required to have the characteristics of easy coating, easy removal, no stimuli, moderate consistency, and no damage to the instrument probe. During the use of the ultrasonic couplant, cross-contamination of skin diseases occurs, especially in the case of skin invasiveness and cross-infection of ultrasound examination when in contact with mucous membranes. According to the biological evaluation concept, the product is “cytotoxic, non-sensitizing and non-irritating to the skin under short-term (24h) contact conditions.” China's “Disinfection Management” Article 6 requires that medical devices and equipment that meet skin and mucous membranes must meet disinfection requirements to prevent and reduce the chance of hospital infections.

However, common ultrasonic coupling agents are widely used on the market, and they do not have a sterilization function, and are prone to cross infection. In addition, among the small number of antibacterial ultrasonic coupling agents currently available on the market, the antibacterial agents are mainly chlorhexidine acetate, povidone iodine, chlorhexidine iodine, p-chloro-xylenol, benzalkonium bromide and the like. On the one hand, these antibacterial agents are not biocompatible and have experienced skin irritation or allergic reactions during use; on the other hand, these antibacterial agents are not biodegradable, once infiltrated during use or due to improper handling When entering the body, it will stay in the body for a long time without being metabolized, resulting in certain toxic side effects.

In summary, the development of an antibacterial medical ultrasonic coupling agent with biocompatibility, biodegradability and simple preparation process has great clinical application value and strong market competitiveness.

Summary of the invention:

The invention provides an antibacterial medical ultrasonic coupling agent, which has the characteristics of good biocompatibility, biodegradability, simple process, low cost and stable performance.

The present invention still further provides a method for preparing an antibacterial medical ultrasonic coupling agent, which is suitable for industrial production.

The invention provides an antibacterial medical ultrasonic coupling agent which is prepared by weighting the following raw materials: carbomer 1%, triethanolamine 0.6%, polyethyleneimine quaternary ammonium salt (1~2) % , PEG (1~2) %, methylene blue (0. 05~0. 1 ) %, fragrance 0. 02%, the balance is distilled water. The preparation method of the antibacterial medical ultrasonic coupling agent of the invention comprises the following steps:

(1) adding carbomer to water, heating and stirring to swell carbomer;

(2) adding a polyethyleneimine quaternary ammonium salt, polyethylene glycol, methylene blue and flavor to the above solution, and continuing to stir to dissolve various raw materials;

(3) Further adding a triethanolamine adjusting solution to a pH of 7.5 to 8.0 to form a pale blue gel, and removing bubbles under vacuum under reduced pressure to obtain a final product.

The viscosity of the product of the invention is between 15.4 and 24.4 Pa.s, the consistency is suitable, the coating performance is good, the biocompatibility is good, the biodegradability is good, and the skin is not stimulated, and the sound attenuation is 0.193 to 0.246 dB.cm-^ ΜΗζ- ¹ , the sound attenuation is small, the sound guiding performance is good, the image is clear, and it can be antibacterial.

The positive effects of the present invention over conventional antibacterial medical ultrasonic coupling agents are:

The polyethyleneimine quaternary ammonium salt with antibacterial agent has good biocompatible phase and biodegradability, no skin irritation, and wide antibacterial spectrum, which greatly reduces the use of ultrasonic couplant during use. Possible cross-infection problems.

Specific lung type:

The following examples are helpful in understanding this patent.

Example 1:

Polycarbomer, polyethyleneimine quaternary ammonium salt, polyethylene glycol (molecular weight 5 000 g / mol), triethanolamine, methylene blue and flavor as raw materials, the specific weight percentage is: carbomer (1.0% Polyethyleneimine quaternary ammonium salt (1.0%), polyethylene glycol (1.0%), triethanolamine (0.6%), methylene blue (0.05%), flavor (0.02%), and the balance is distilled water. Preparation:

(1) Add 1.0 g of carbomer to 96.3 mL of water, heat and stir to swell; (2) 1.0 g of polyethyleneimine quaternary ammonium salt (molecular weight 10 000 g/mol), 1.0 g polyethyl b Glycol, 0.05 g methylene blue and 0.02 g flavor are added to the above solution, and stirring is continued to dissolve various raw materials; (3) 0.6 g of triethanolamine is added, and the pH of the solution is tested after stirring, and a small amount is added as appropriate. Triethanolamine to adjust the pH of the solution between 7.5 and 8.0 to form a pale blue gel; (4) Remove the bubbles under vacuum and reduce the pressure to obtain the final product.

Physical and chemical properties of the coupling agent:

The physical and chemical properties of Example 1 are shown in Table 1, and the results showed that the viscosity was suitable and the sound attenuation was small.

Table 1. Physical and chemical properties of Example 1

Serial number indicator result 1 pH 7.1

2 viscosity 15.4 Pa.s

3 acoustic impedance 1.66 X 10 ⁶ Pa sm- ¹

4 sound attenuation 0.233

5 sound speed 1630 ms - ¹ clinical application effect test:

The couplant of Example 1 was tested for clinical application, and the results showed that the couplant was easy to coat, has good slidability, no damage to the ultrasonic probe, and no stimulation to the skin. The coupling of the couplant of Example 1 to the ultrasonic probe and the skin The effect is good and the image obtained is clear.

Example 2:

Polycarbomer, polyethyleneimine quaternary ammonium salt (molecular weight 10 000 g / mol), polyethylene glycol (molecular weight 5 000 g / mol), triethanolamine, methylene blue and flavor as raw materials, specific weight Percentages are: Carbomer (1.0%) Polyethyleneimine quaternary ammonium salt (1.0%), polyethylene glycol (1.5%), triethanolamine (0.6%), methylene blue (0.05%), flavor (0.02%) ), the balance is steamed water.

Preparation:

(1) Add 1.0 g of carbomer to 95.8 mL of water, heat and stir to swell; (2) 1.0 g of polyethyleneimine quaternary ammonium salt, 1.5 g of polyethylene glycol, 0.05 g of methylene blue and Add 0.02 g of the essence to the above solution, continue to stir, and dissolve the various raw materials; (3) Add 0.6 g of triethanolamine, stir the pH of the solution, and add a small amount of triethanolamine as appropriate to adjust the pH of the solution. A light blue gel is formed between 7.5 and 8.0; (4) bubbles are removed under vacuum to obtain a final product.

Physical and chemical properties of the coupling agent:

The physical and chemical properties of Example 2 are shown in Table 2, and the results showed that the viscosity was suitable and the sound attenuation was small.

Table 2. Physical and chemical properties of Example 2

No. Indicator Result

1 pH 7· 3

2 Viscosity 16.0 Pa.s

3 Acoustic impedance 1· 59 X 10 ⁶ Pa.sm—

4 sound attenuation 0.246

Sound speed 1840 ms Clinical application effect detection:

The couplant of Example 2 was tested for clinical application, and the results showed that the couplant was easy to coat, has good slidability, no damage to the ultrasonic probe, and no stimulation to the skin. The coupling of the couplant of Example 2 to the ultrasonic probe and the skin The effect is good and the image obtained is clear.

Example 3:

Polycarbomer, polyethyleneimine quaternary ammonium salt (molecular weight 10 000 g / mol), polyethylene glycol (molecular weight 5 000 g / mol), triethanolamine, methylene blue and flavor as raw materials, specific weight Percentages are: Carbomer (1.0%) Polyethyleneimine quaternary ammonium salt (1.5%), polyethylene glycol (1.0%), triethanolamine (0.6%), methylene blue (0.10%), flavor (0.02%) ), the balance is steamed water.

Preparation:

(1) Add 1.0 g of carbomer to 95.8 mL of water, heat and stir to swell; (2) 1.5 g of polyethyleneimine quaternary ammonium salt, 1.0 g of polyethylene glycol, 0.10 g of methylene blue and Add 0.02 g of the essence to the above solution, continue to stir, and dissolve the various raw materials; (3) Add 0.6 g of triethanolamine, stir the pH of the solution, and add a small amount of triethanolamine as appropriate to adjust the pH of the solution. A light blue gel is formed between 7.5 and 8.0; (4) bubbles are removed under vacuum to obtain a final product.

Physical and chemical properties of the coupling agent:

The physical and chemical properties of Example 3 are shown in Table 3, and the results showed that the viscosity was suitable and the sound attenuation was small.

Table 3. Physical and chemical properties of Example 3

No. Indicator Result

1 pH 7.4

2 viscosity 15.5 Pa.s

3 acoustic impedance 1.64 X 10 ⁶ Pa.sm- ¹

4 sound attenuation 0.238

5 sound speed 1610 ms - ¹ clinical application effect test:

The couplant of Example 3 was tested for clinical application, and the results showed that the couplant was easy to coat and had good slidability. There is no damage to the ultrasonic probe and no stimulation to the skin. The coupling agent of the embodiment 3 has a good coupling effect on the ultrasonic probe and the skin, and the obtained image is clear.

Example 4:

Polycarbomer, polyethyleneimine quaternary ammonium salt (molecular weight 10 000 g / mol), polyethylene glycol (molecular weight 5 000 g / mol), triethanolamine, methylene blue and flavor as raw materials, specific weight Percentage: Carbomer (1.0%) Polyethyleneimine quaternary ammonium salt (2.0%), polyethylene glycol (1.5%), triethanolamine (0.6%), methylene blue (0.05%), flavor (0.02%) ), the balance is steamed water.

Preparation:

(1) Add 1.0 g of carbomer to 94.8 mL of water, heat and stir to swell; (2) 2.0 g of polyethyleneimine quaternary ammonium salt, 1.5 g of polyethylene glycol, 0.05 g of methylene blue and Add 0.02 g of the essence to the above solution, continue to stir, and dissolve the various raw materials; (3) Add 0.6 g of triethanolamine, stir the pH of the solution, and add a small amount of triethanolamine as appropriate to adjust the pH of the solution. A light blue gel is formed between 7.5 and 8.0; (4) bubbles are removed under vacuum to obtain a final product.

Physical and chemical properties of the coupling agent:

The physical and chemical properties of Example 4 are shown in Table 4, and the results showed that the viscosity was suitable and the sound attenuation was small.

Table 4. Physical and chemical properties of Example 4

No. Indicator Result

1 pH 7.1

2 viscosity 17.2 Pa.s

3 acoustic impedance 1.68 X 10 ⁶ Pa.sm- ¹

4 sound attenuation 0.229

5 sound speed 1650 ms - ¹ clinical application effect detection:

The couplant of Example 4 was tested for clinical application, and the results showed that the couplant was easy to coat, has good slidability, no damage to the ultrasonic probe, and no stimulation to the skin. The coupling of the couplant of Example 4 to the ultrasonic probe and the skin The effect is good and the image obtained is clear.

Example 5

Polycarbomer, polyethyleneimine quaternary ammonium salt (molecular weight 30 000 g/mol), polyethylene glycol (molecular weight 5 000 g / mol), triethanolamine, methylene blue and flavor as raw materials, the specific weight percentage is: carbomer (1.0%) polyethyleneimine quaternary ammonium salt (2.0%), polyethylene glycol (1.0%) , triethanolamine (0.6%), methylene blue (0.1%), essence (0.02%), the balance is distilled water.

Preparation:

(1) Add 1.0 g of carbomer to 95.3 mL of water, heat and stir to swell; (2) 2.0 g of polyethyleneimine quaternary ammonium salt, 1.0 g of polyethylene glycol, 0.1 g of methylene blue and Add 0.02 g of the essence to the above solution, continue to stir, and dissolve the various raw materials; (3) Add 0.6 g of triethanolamine, stir the pH of the solution, and add a small amount of triethanolamine as appropriate to adjust the pH of the solution. A light blue gel is formed between 7.5 and 8.0; (4) bubbles are removed under vacuum to obtain a final product.

Physical and chemical properties of the coupling agent:

The physical and chemical properties of Example 5 are shown in Table 5. The results showed that the viscosity was suitable and the sound attenuation was small.

Table 5. Physical and chemical properties of Example 5

No. Indicator Result

1 pH 7.4

2 Viscosity 24.4 Pa.s

3 acoustic impedance 1.88 X10 ⁶ Pa.sm- ¹

4 sound attenuation 1710 ms- ¹

5 speed of sound 1430 ms - ¹ clinical application effect detection:

The couplant of Example 5 was tested for clinical application, and the results showed that the couplant was easy to coat, no damage to the ultrasonic probe, and no stimulation to the skin. The coupling agent of Example 5 had a good coupling effect on the ultrasonic probe and the skin. The images obtained are clear.

Example 6:

Polycarbomer, polyethyleneimine quaternary ammonium salt (molecular weight 30 000 g / mol), polyethylene glycol (molecular weight 5 000 g / mol), triethanolamine, methylene blue and flavor as raw materials, specific weight Percentages are: Carbomer (1.0%) Polyethyleneimine quaternary ammonium salt (1.5%), polyethylene glycol (1.5%), triethanolamine (0.6%), methylene blue (0.05%), flavor (0.02%) ), the balance is steamed water.

Preparation: (1) 1. 0 g of carbomer is added to 95.3 mL of water, heated and stirred to swell; (2) 1.5 g of polyethyleneimine quaternary ammonium salt, 1. 5 g of polyethylene Alcohol, 0. 05 g methylene blue and 0. 02 g of perfume added to the above solution, continue to stir, so that the various raw materials are dissolved; (3) add 0. 6 g of triethanolamine, the pH of the test solution after stirring, as appropriate A small amount of triethanolamine is added dropwise to adjust the pH of the solution to between 7. 5 and 8. 0 to form a pale blue gel; (4) to remove bubbles under vacuum and reduced pressure to obtain a final product.

Physical and chemical properties of the coupling agent:

The physical and chemical properties of Example 6 are shown in Table 6, and the results showed that the viscosity was suitable and the sound attenuation was small.

Table 6. Physical and chemical properties of Example 6

No. Indicator Result

1 pH 7. 2

2 Viscosity 21. 9 Pa.s

3 Acoustic impedance 1. 75 X 10 ⁶ Pa.sm- ¹

4 sound attenuation 0. 193

5 sound speed 1500 ms - ¹ clinical application effect test:

The couplant of Example 6 was tested for clinical application, and the results showed that the couplant was easy to coat, no damage to the ultrasonic probe, and no stimulation to the skin, and the coupling agent of Example 6 had a good coupling effect on the ultrasonic probe and the skin. The images obtained are clear.

Experimental Example 1: Antibacterial effect of antibacterial medical ultrasonic coupling agent

1. 1 Experimental purpose:

The antibacterial effect of the antibacterial medical ultrasonic coupling agent prepared by the present invention was examined and compared with the products on the market.

1. 2 Experimental instruments and raw materials:

Siemens ACUS0N X150 ultrasonic diagnostic system, antibacterial ultrasonic coupling agent prepared by the invention, Changchun Xingshi antibacterial ultrasonic coupling agent, sound friend brand medical antibacterial disinfection type ultrasonic coupling agent, 5cmX 5cm sterilization specification plate, sterile washing Deliquoring, cotton swabs, saline, nutrient agar medium, distilled water.

1. 3 Experimental methods:

The method used in this experiment is strictly implemented in accordance with the "Sanitary Standard for Sanitary Hygiene Products GB15979-1995". The specific experimental method will be described below by taking Example 1 as an example. Different ratios of the ultrasonic coupling agents prepared in the examples were subjected to ultrasonic examination.

1. 3. 1 sampling

Before the ultrasonography, the abdominal skin was first sampled as a control; after the ultrasonic examination was applied for 1 hour, the skin of the same abdominal examination area was sampled again.

The sampling method is carried out in accordance with the "Technical Disinfection Technical Specification - 2012 Edition", specifically: using a 5cmX 5cm sterilized specification plate, placed on the skin to be inspected, and immersed in cotton with a sterile eluate containing the corresponding neutralizing agent. 1 swab, rub it evenly in the specification plate for 5 times, and then rotate the cotton swab. After cutting the hand contact area, put the cotton swab into 200mL sterile saline, mix well and get A saline solution, for testing.

1. 3. 2 detection

Take the physiological saline supernatant in 1.3.1 for the colony count of the sample to be tested. A total of 5 plates were inoculated, and 1 mL of the sample to be tested was added to each plate, and then 15-20 mL of the melted nutrient agar medium cooled to about 45 ° C was poured into each plate and mixed well. After the agar was solidified, the plate was placed at 35 ° C ± 2 ° C for 48 hours, and the number of colonies on the plate was counted.

1. 3. 3 Calculation of colony number

Plates with colonies grown in flakes should not be used; count colonies on plates that meet the requirements, and calculate the results as follows: 3⁄4=A*K/5

Where: - the total number of bacterial colonies, the unit is cfu / mL;

The total number of bacterial colonies on the A-5 agar medium plate;

K - dilution.

1. 3. 4 Results and discussion

Using the same method, the examples 2 to 6, the Changchun Xingshi bacteriostatic ultrasonic coupling agent and the vocal brand antibacterial disinfection type ultrasonic coupling agent were respectively tested. The test results are shown in Table 7, for the skin to be examined. The number of colonies after 1 hour of ultrasound examination was much lower than the number of colonies before ultrasound examination, indicating that the various ratios of ultrasonic coupling agents prepared in Example 1 and the two marketed ultrasonic coupling agents have excellent antibacterial properties. effect. Ultrasound examination was performed using the ultrasonic coupling agent of the present example, and the number of colonies after ultrasonic examination for 1 hour was between 64 and 88 cfu/mL, and two commercially available products were used for ultrasonic examination, one hour after the ultrasonic examination. The number of colonies is greater than 90 cfu/mL, indicating that the antibacterial medical ultrasonic coupling agent of the present invention has a better antibacterial effect.

Table 7. Antibacterial effect detection of ultrasonic coupling agent Number of colonies before ultrasonic examination Ultrasound examination number of colonies after 1 hour cfu/mL cfu/mL Example 1 9310 82 Example 2 9040 64 Example 3 9300 78 Example 4 8200 87 Example 5 8870 74 Example 6 9250 88

声友 9070 91 Changchun Xingshi 9190 92

Claims

1. An antibacterial medical ultrasonic coupling agent made from the following raw materials in percentage by weight:

Carbomer 1%, triethanolamine 0.6%, polyethyleneimine quaternary ammonium salt (1~2)%, polyethylene glycol (1~2)%, methylene blue (0.05~0.1)%, flavor 0.02%, The balance is steamed water.

2. The method of preparing an antibacterial medical ultrasonic coupling agent according to claim 1, comprising the steps of:

(1) adding carbomer to water, heating and stirring to swell carbomer;

(2) adding polyethyleneimine quaternary ammonium salt, polyethylene glycol, methylene blue and flavor to the above solution, and stirring is continued to dissolve various raw materials;

(3) Adding triethanolamine to adjust the pH of the solution to between 7.5 and 8.0, forming a pale blue gel, and removing the bubbles under vacuum and reduced pressure.