KR20160046907A - Antibacterial medical ultrasonic coupling agent and preparation method thereof - Google Patents

Abstract

The present invention relates to an antibacterial medical ultrasound coupling agent and a process for producing the same, wherein the polyethyleneimine quaternary ammonium salt is 1 to 2%, the polyethylene glycol is 1 to 2%, and the methylene blue is 0.05 to 5% 0.1%, and the rest is distilled water. In the method for producing an antibacterial medical ultrasound coupling agent, various raw materials and water are mixed according to the ratio, and then the mixture is heated while being melted and swollen. Finally, the vacuum is reduced in vacuum to remove air bubbles. .

Description

TECHNICAL FIELD [0001] The present invention relates to an antibacterial medical ultrasound coupling agent, and an antibacterial ultrasound coupling agent.

The present invention relates to an antibacterial medical ultrasound coupling agent. The present invention further provides a method for producing the above coupling agent, and belongs to the technical field of reagent for medical examination.

The B type ultrasound diagnostic device is used extensively in the clinic. The medical ultrasound coupling agent used for the medical examination is applied to the skin of the measurement site to remove the air between the probe and the skin of the device. . Therefore, the ultrasonic coupling agent is required to be easy to apply, easy to remove, free of irritation, suitable in concentration, and not damaging the probe of the device. During the use of ultrasound coupling agents, cross-contamination of skin diseases, particularly skin contact or contact with mucous membranes, can lead to cross infection in the course of ultrasound examination. In the "Standard for Medical Ultrasonic Coupling Agents" written by New Funchi et al., "Biological evaluation concept requiring the product to be acellular toxicity, no sensitization, no stimulation to the skin" under conditions of contact for a short time (24 h) China "How to Manage Disinfection" According to the requirements of Article 6, all machinery and supplies that contact the skin and mucous membranes in a medical sanitary institution must meet the disinfection requirements to reduce the probability of infection in the hospital.

However, currently used ultrasonic coupling agents widely used in the market are general ultrasonic coupling agents, they do not have sterilization function, and cross-infection can easily occur. In addition, among the existing small quantities of antimicrobial ultrasound coupling agents on the market, antimicrobial agents are mainly chlorhexidine acetate, povidone-iodine, chlorhexidine iodine, para-chloromethacylenol parachlorometoxylenol, benzalkonium bromide, and the like. On the other hand, these antimicrobial agents do not have biocompatibility and have been exposed to skin irritation or hypersensitivity during use; On the other hand, since these antimicrobial agents do not have biodegradability, they are not metabolized for a relatively long period of time in the body once they have penetrated into the body due to osmosis or improper manipulation during use. have.

Taken together, the above developments show that the development of a biocompatible, biodegradable, and simple process for producing an antibacterial medical ultrasound coupling agent has a relatively high clinical application value and a relatively strong market competitiveness.

The present invention provides an antibacterial medical ultrasound coupling agent having good biocompatibility, biodegradable, simple process, low cost, and stable performance.

The present invention further provides a method for producing an antibacterial medical ultrasound coupling agent applied to industrial production.

The antibacterial medical ultrasound coupling agent provided by the present invention comprises 1% of carbomer, 0.6% of triethanolamine, 1 to 2% of polyethyleneimine quaternary ammonium salt, 1 to 2% of Polyethylene glycol, 0.05 to 0.1% methylene blue, 0.02% essence, and the balance being distilled water.

In the method for producing an antibacterial medical ultrasound coupling agent of the present invention,

(1) adding a carbomer to water and heating and stirring the carbomer until it swells;

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

(3) triethanolamine is then added to adjust the pH of the solution to between 7.5 and 8.0 to form a light blue gel, vacuum is applied in vacuum to remove air bubbles to obtain final product

.

The viscosity of the product of the present invention is in the range of 15.4 to 24.4 Pa · s, the concentration is appropriate, the application performance is good, the biocompatibility is good, the biodegradability is possible, the skin is not stimulated and the sound attenuation is 0.193 to 0.246 dB .Cm ^-1 .MHz ^-1 , sound attenuation is low, sound conductivity is good, the image is clear, and it is capable of antimicrobial disinfection.

The positive effects of the present invention and the conventional antibacterial medical ultrasound coupling agent are as follows.

The polyethyleneimine quaternary ammonium salt having antimicrobial activity has comparatively good biocompatibility and biodegradability, has no irritation to the skin, has a strong antimicrobial action, and thus has a wide use range. Therefore, the cross- Reduce the problem as much as possible.

The following examples are advantageous for understanding this patent.

Example 1:

Polyethylene glycol (having a molecular weight of 5000 g / mol), triethanolamine, methylene blue and essence as raw materials, and specific weight percentages are as follows. The carbonomer is 1.0%, the polyethyleneimine quaternary ammonium salt is 1.0%, the polyethylene glycol is 1.0%, the triethanolamine is 0.6%, the methylene blue is 0.05%, the essence is 0.02%, and the rest is distilled water.

Manufacturing method:

(1) Take 1.0 g of carbomer and add to 96.3 mL of water and stir while heating until the solution swells; (2) 1.0 g of a polyethyleneimine quaternary ammonium salt (with a molecular weight of 10000 g / mol), 1.0 g of polyethylene glycol, 0.05 g of methylene blue and 0.02 g of essence were added to the solution and the mixture was continuously stirred to dissolve various raw materials ; (3) 0.6 g of triethanolamine was added and stirred. Then, the pH value of the solution was tested. A small amount of triethanolamine was added dropwise continuously to adjust the pH value of the solution to 7.5 to 8.0, To form a gel; (4) Vacuum is performed under reduced pressure to remove bubbles to obtain final product.

Physicochemical performance of coupling agent:

The physicochemical performance of Example 1 is as shown in Table 1 and the results show that its viscosity is adequate and sound attenuation is low.

The physicochemical performance of Example 1 Sequence number Indicators result One pH value 7.1 2 Viscosity 15.4 Pa.s 3 Sound resistance 1.66 × 10 ⁶ Pa.sm ^-1 4 Sound attenuation 0.233 dB.cm ^-1. M? Hz ^-1 5 Sound speed 1630 ms ^-1

Clinical application effectiveness measurement:

As a result of clinical application measurement of the coupling agent of Example 1, it was found that the coupling agent was easy to apply, had good sliding properties, had no damage to the ultrasonic probe, and had no irritation to the skin. It shows that the coupling effect on ultrasonic probe and skin is good and the obtained image is clear.

Example 2:

The weight percentages are as follows: Polycarbonate, polyethyleneimine quaternary ammonium salt (molecular weight is 10000 g / mol), polyethylene glycol (molecular weight is 5000 g / mol), triethanolamine, methylene blue and essence are as follows. 1.0%, the polyethyleneimine quaternary ammonium salt is 1.0%, the polyethylene glycol is 1.5%, the triethanolamine is 0.6%, the methylene blue is 0.05%, the essence is 0.02%, and the rest is distilled water.

Manufacturing method:

(1) Take 1.0 g of carbomer and add to 95.8 mL of water and stir while heating until the solution swells; (2) 1.0 g of polyethyleneimine quaternary ammonium salt, 1.5 g of polyethylene glycol, 0.05 g of methylene blue and 0.02 g of essence were added to the solution to continue stirring to dissolve various raw materials; (3) 0.6 g of triethanolamine was added and stirred. Then, the pH value of the solution was tested. A small amount of triethanolamine was added dropwise continuously to adjust the pH value of the solution to 7.5 to 8.0, To form a gel; (4) Vacuum is performed under reduced pressure to remove bubbles to obtain final product.

Physicochemical performance of coupling agent:

The physicochemical performance of Example 2 is as shown in Table 2 and the results show that its viscosity is adequate and sound attenuation is low.

The physicochemical performance of Example 2 Sequence number Indicators result One pH value 7.3 2 Viscosity 16.0 Pa.s 3 Sound resistance 1.59 x 10 < ⁶ > Pa.sm ^-1 4 Sound attenuation 0.246 dB.cm ^{- 1} .mu.m ^{-1 -1} 5 Sound speed 1840 ms ^-1

Clinical application effectiveness measurement:

As a result of clinical application measurement of the coupling agent of Example 2, it was found that the coupling agent was easy to apply, had good sliding properties, had no damage to the ultrasonic probe, had no irritation to the skin, It shows that the coupling effect on ultrasonic probe and skin is good and the obtained image is clear.

Example  3:

Polyethylene glycol (molecular weight is 5000 g / mol), triethanolamine, methylene blue and essence are used as raw materials, and the specific weight percentages are as follows. The carbomer is 1.0%, the polyethyleneimine quaternary ammonium salt is 1.5%, the polyethylene glycol is 1.0%, the triethanolamine is 0.6%, the methylene blue is 0.10%, the essence is 0.02%, and the rest is distilled water.

Manufacturing method:

(1) Take 1.0 g of carbomer and add to 95.8 mL of water and stir while heating until the solution swells; (2) 1.5 g of a polyethyleneimine quaternary ammonium salt, 1.0 g of polyethylene glycol, 0.10 g of methylene blue and 0.02 g of essence are added to the solution to continue stirring to dissolve various raw materials; (3) 0.6 g of triethanolamine was added and stirred. Then, the pH value of the solution was tested. A small amount of triethanolamine was added dropwise continuously to adjust the pH value of the solution to 7.5 to 8.0, To form a gel; (4) Vacuum is performed under reduced pressure to remove bubbles to obtain final product.

Physicochemical performance of coupling agent:

The physicochemical performance of Example 3 is as shown in Table 3 and the results show that its viscosity is adequate and sound attenuation is low.

The physico-chemical performance of Example 3 Sequence number Indicators result One pH value 7.4 2 Viscosity 15.5 Pa.s 3 Sound resistance 1.64 × 10 ⁶ Pa.sm ^-1 4 Sound attenuation 0.238 dB.cm ^-1 . ΜΗz ^-1 5 Sound speed 1610 ms ^-1

Clinical application effectiveness measurement:

As a result of clinical application measurement of the coupling agent of Example 3, it was found that the coupling agent was easy to apply, had good sliding properties, had no damage to the ultrasonic probe, had no irritation to the skin, It shows that the coupling effect on ultrasonic probe and skin is good and the obtained image is clear.

Example  4:

Polyethylene glycol (molecular weight is 5000 g / mol), triethanolamine, methylene blue and essence are used as raw materials, and the specific weight percentages are as follows. The carbomer is 1.0%, the polyethyleneimine quaternary ammonium salt is 2.0%, the polyethylene glycol is 1.5%, the triethanolamine is 0.6%, the methylene blue is 0.05%, the essence is 0.02%, and the rest is distilled water.

Manufacturing method:

(1) Take 1.0 g of carbomer and add to 94.8 mL of water and stir while heating until the solution swells; (2) 2.0 g of polyethyleneimine quaternary ammonium salt, 1.5 g of polyethylene glycol, 0.05 g of methylene blue and 0.02 g of essence were added to the solution to continue to stir the various raw materials to dissolve; (3) 0.6 g of triethanolamine was added and stirred. Then, the pH value of the solution was tested. A small amount of triethanolamine was added dropwise continuously to adjust the pH value of the solution to 7.5 to 8.0, To form a gel; (4) Vacuum is performed under reduced pressure to remove bubbles to obtain final product.

Physicochemical performance of coupling agent:

The physicochemical performance of Example 4 is as shown in Table 4 and the results show that its viscosity is adequate and sound attenuation is low.

The physico-chemical performance of Example 4 Sequence number Indicators result One pH value 7.1 2 Viscosity 17.2 Pa.s 3 Sound resistance 1.68 × 10 ⁶ Pa.sm ^-1 4 Sound attenuation 0.229 dB.cm ^{- 1} .mu.m ^{-1 -1} 5 Sound speed 1650 ms ^-1

Clinical application effectiveness measurement:

As a result of clinical application measurement of the coupling agent of Example 4, it was found that the coupling agent was easy to apply, had good sliding properties, was free of damage to the ultrasonic probe, and had no irritation to the skin. It shows that the coupling effect on ultrasonic probe and skin is good and the obtained image is clear.

Example  5:

(Molecular weight is 30000 g / mol), polyethylene glycol (molecular weight is 5000 g / mol), triethanolamine, methylene blue and essence are used as raw materials, and specific weight percentages are as follows. The carbomer is 1.0%, the polyethyleneimine quaternary ammonium salt is 2.0%, the polyethylene glycol is 1.0%, the triethanolamine is 0.6%, the methylene blue is 0.1%, the essence is 0.02%, and the rest is distilled water.

Manufacturing method:

(1) Take 1.0 g of carbomer and add to 95.3 mL of water and stir while heating until the solution swells; (2) 2.0 g of a polyethyleneimine quaternary ammonium salt, 1.0 g of polyethylene glycol, 0.1 g of methylene blue and 0.02 g of essence were added to the solution to continue stirring to dissolve various raw materials; (3) 0.6 g of triethanolamine was added and stirred. Then, the pH value of the solution was tested. A small amount of triethanolamine was added dropwise continuously to adjust the pH value of the solution to 7.5 to 8.0, To form a gel; (4) Vacuum is performed under reduced pressure to remove bubbles to obtain final product.

Physicochemical performance of coupling agent:

The physicochemical performance of Example 5 is as shown in Table 5 and the results show that its viscosity is adequate and sound attenuation is low.

The physical and chemical performance of Example 5 Sequence number Indicators result One pH value 7.4 2 Viscosity 24.4 Pa.s 3 Sound resistance 1.88 × 10 ⁶ Pa.sm ^-1 4 Sound attenuation 1710 ms ^-1 5 Sound speed 1430 ms ^-1

Clinical application effectiveness measurement:

As a result of clinical application measurement of the coupling agent of Example 5, it was found that the coupling agent was easy to apply, there was no damage to the ultrasonic probe, no irritation to the skin, and the coupling agent of Example 5 was an ultrasonic probe and skin The coupling effect is good and the image obtained is clear.

Example 6:

(Molecular weight is 30000 g / mol), polyethylene glycol (molecular weight is 5000 g / mol), triethanolamine, methylene blue and essence are used as raw materials, and specific weight percentages are as follows. The carbonomer is 1.0%, the polyethyleneimine quaternary ammonium salt is 1.5%, the polyethylene glycol is 1.5%, the triethanolamine is 0.6%, the methylene blue is 0.05%, the essence is 0.02%, and the rest is distilled water.

Manufacturing method:

(1) Take 1.0 g of carbomer and add to 95.3 mL of water and stir while heating until the solution swells; (2) 1.5 g of polyethyleneimine quaternary ammonium salt, 1.5 g of polyethylene glycol, 0.05 g of methylene blue and 0.02 g of essence are added to the solution to continue stirring to dissolve various ingredients; (3) 0.6 g of triethanolamine was added and stirred. Then, the pH value of the solution was tested. A small amount of triethanolamine was added dropwise continuously to adjust the pH value of the solution to 7.5 to 8.0, To form a gel; (4) Vacuum is performed under reduced pressure to remove bubbles to obtain final product.

Physicochemical performance of coupling agent:

The physicochemical performance of Example 6 is as shown in Table 6 and the results show that its viscosity is adequate and sound attenuation is low.

The physical and chemical performance of Example 6 Sequence number Indicators result One pH value 7.2 2 Viscosity 21.9 Pa.s 3 Sound resistance 1.75 × 10 ⁶ Pa.sm ^-1 4 Sound attenuation 0.193 dB.cm ^{- 1} .mu.m ^{-1 -1} 5 Sound speed 1500 ms ^-1

Clinical application effectiveness measurement:

As a result of the clinical application measurement of the coupling agent of Example 6, it was found that the coupling agent was easy to apply, there was no damage to the ultrasonic probe, no irritation to the skin, and the coupling agent of Example 6 had an ultrasonic probe and skin The coupling effect is good and the image obtained is clear.

Experimental Example  1: Antibacterial Ultrasonic Medical Coupling agent  Measurement of bacterial growth inhibition

1.1 Purpose of experiment:

The bacterial propagation inhibitory effect of the antibacterial medical ultrasound coupling agent prepared in the present invention is measured and the products in the current market are compared.

1.2 Experimental apparatus and raw materials:

)의 세균번식 억제 초음파 커플링제, 성유(

) 브랜드의 의료용 세균번식 억제 소독 타입 초음파 커플링제, 5cm × 5cm인 멸균 규격판(sterilizing etalon board), 무균 용출액, 면봉, 생리 식염수, 한천배지(nutrient agar), 증류수.An ACUS0N X150 ultrasonic diagnostic system from Siemens, an antibacterial ultrasonic coupling agent manufactured by the present invention,

), A bacterial propagation-suppressing ultrasonic coupling agent,

Sterilizing etalon board, sterile eluent, cotton swab, saline solution, nutrient agar, distilled water, and the like.

1.3 Experimental Method:

The method used in this experiment is strictly conducted in accordance with the hygiene standard (GB15979-1995) using disposable hygiene products.

A concrete experimental method will be described by taking the example 1 below as an example. Ultrasonic inspection is performed on the ultrasonic coupling agents having different distribution ratios produced in the examples.

1.3.1 Sampling

Before proceeding with the ultrasound examination, first, the abdominal skin is sampled and referenced; The ultrasonic examination is performed for 1 hour by applying the first embodiment, and then the skin of the abdominal region to be inspected of the same part is sampled again.

The sampling method is carried out according to the <Medical Institution Disinfection Technical Standard -2012>, and the specific method is as follows. Using a sterilized standard plate of 5 cm x 5 cm, place on the area of the skin to be examined and rub uniformly five times each in a reciprocal manner in the longitudinal direction using a single swab with a sterile effluent containing the corresponding neutralizing agent , The swab is turned and the area in contact with the hands is cut off. Then, the swab is put into 200 mL of sterile physiological saline and thoroughly homogeneously mixed to obtain one physiological saline sample solution, which is prepared for examination.

1.3.2 Measurement

Take the physiological saline supernatant from 1.3.1 and count bacterial colonies for the sample solution to be determined. After adding 1 mL of the sample solution to be measured to each petri dish, cool the solution to 45 ° C and pour 15-20 mL of the agar medium, which has been melted, into each Petri dish. . After the agar coagulates, the Petri dish is turned over and incubated at 35 ° C ± 2 ° C for 48 h, then the number of colonies on the Petri dish is calculated.

1.3.3 Number of Colonies

Petri dishes grown colony are not suitable for use; The colonies on the Petri dish corresponding to the requirement are counted, and the result is calculated according to the following formula.

X ₁ = A * K / 5

In the formula, X ₁ is the total number of bacterial colonies, and the unit is cfu / mL;

A is the total number of bacterial colonies on the five agar media;

K is the degree of dilution.

1.3.4 Results and Discussion

)의 세균번식 억제 초음파 커플링제 및 성유(

) 브랜드의 의료용 세균번식 억제 소독 타입 초음파 커플링제에 대해 각각 측정을 진행하면, 측정 결과는 표 7과 같고, 검사 받을 피부에 있어서, 초음파 검사를 1시간 동안 진행한 후의 콜로니수는 초음파 검사를 진행하기 전의 콜로니수보다 많이 적고, 실시예 1에서 제조된 상이한 배분율의 각종 초음파 커플링제 및 시장화된 두가지 초음파 커플링제는 모두 아주 좋은 항균 효과를 구비한다는 것을 보여준다. 본 실시예의 초음파 커플링제를 응용하여 초음파 검사를 진행하면, 초음파 검사를 1시간 동안 진행한 후의 콜로니수는 64 내지 88 cfu/mL 사이에 있으나, 시중에서 구매한 두 가지 제품을 응용하여 초음파 검사를 진행하면, 초음파 검사를 1시간 동안 진행한 후의 콜로니수가 모두 90 cfu/mL보다 큰데, 이는 본 발명의 항균성 의료용 초음파 커플링제가 보다 좋은 항균 효과를 구비한다는 것을 설명한다.By applying the same method, Examples 2 to 6, Changchun Thinks (

) For the inhibition of germ propagation and ultrasound coupling agents

), The results of measurement are as shown in Table 7. The number of colonies after the ultrasonic examination for 1 hour was examined in the skin to be examined, and the number of colonies after the ultrasonic examination was subjected to ultrasonic examination The number of colonies before use, and the various types of the various ultrasound coupling agents prepared in Example 1 and the two commercially available ultrasound coupling agents all have a very good antibacterial effect. When the ultrasonic wave is applied by the ultrasonic coupling agent of the present embodiment, the number of colonies after the ultrasonic examination for 1 hour is in the range of 64 to 88 cfu / mL. However, When proceeded, the number of colonies after the one-hour ultrasound examination is greater than 90 cfu / mL, which explains that the antibacterial medical ultrasound coupling agent of the present invention has a better antimicrobial effect.

Ultrasonic coupling agent Measurement of bacterial propagation inhibition Before ultrasound examination
Number of colonies
cfu / mL Ultrasonography was performed for 1 hour
Number of colonies after progression
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

)chrism(

) 9070 91 Changchun Thinks (

) 9190 92

Claims (2)

1% of carbomer, 0.6% of triethanolamine, 1 to 2% of polyethyleneimine quaternary ammonium salt, 1 to 2% of polyethylene glycol, 0.05 to 0.1% Of methylene blue, 0.02% essence, and the remainder being distilled water, based on the weight percentage. (1) adding a carbomer to water and heating and stirring the carbomer until it swells;
(2) adding polyethyleneimine quaternary ammonium salt, polyethylene glycol, methylene blue and essence to the solution and continuing to stir the various raw materials to dissolve;
(3) triethanolamine is then added to adjust the pH of the solution to between 7.5 and 8.0 to form a light blue gel, followed by reduced pressure in vacuo to remove air bubbles to obtain the final product A method for producing an ultrasonic coupling agent for antibacterial medical use according to claim 1.

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