阅读说明：本技术 医用消毒杀菌型超声耦合剂 (Medical disinfection sterilization type ultrasonic coupling agent ) 是由 陈芗茹 冯冲 张欣 孟庆鑫 张庆雨 宋爽 付万兴 于 2019-10-14 设计创作，主要内容包括：本发明涉及一种医用消毒杀菌型超声耦合剂。本发明发现了式(I)化合物在杀菌方面的作用,进而将其应用于消毒杀菌型超声耦合剂中,从而为消毒杀菌型超声耦合剂提供了更多选择。试验结果表明,本发明所述式(I)化合物具有突出的杀菌效果,因而本发明的医用消毒杀菌型超声耦合剂可以仅包含较低浓度的杀菌剂,并实现了很好的杀菌和抑菌效果。此外,本发明的医用消毒杀菌型超声耦合剂符合国家标准,其对皮肤粘膜无刺激、无致敏、细胞毒性0级,因此适用在各种超声环境下使用,特别适合在要求较高无菌条件的场合使用,如手术中、烧烫伤以及人体自然腔道内等。(The invention relates to a medical disinfection sterilization type ultrasonic coupling agent. The invention discovers the function of the compound shown in the formula (I) in the aspect of sterilization, and further applies the compound to the sterilization type ultrasonic couplant, thereby providing more choices for the sterilization type ultrasonic couplant. The test result shows that the compound of the formula (I) has an outstanding sterilization effect, so that the medical disinfection sterilization type ultrasonic coupling agent can only contain a low-concentration bactericide, and realizes good sterilization and bacteriostasis effects. In addition, the medical disinfection sterilization type ultrasonic coupling agent meets the national standard, has no stimulation, sensitization and cytotoxicity of 0 grade on skin mucosa, is suitable for being used in various ultrasonic environments, and is particularly suitable for being used in occasions requiring high sterile conditions, such as operations, burns and scalds, natural body cavities and the like.)

1. A medical disinfection sterilization type ultrasonic couplant, comprising:

wherein the bactericide is a compound of the following formula (I) or a pharmaceutically acceptable salt thereof:

2. the medical disinfecting and sterilizing ultrasonic couplant of claim 1, wherein the aqueous gel matrix is selected from one or more of carbomer, hydroxyethyl cellulose, hydroxypropyl cellulose and sodium carboxymethyl cellulose, and preferably carbomer.

3. The medical disinfecting and sterilizing ultrasonic couplant of claim 2, wherein the carbomer is selected from one or more of carbomer 940, carbomer 941, carbomer 1342 or carbomer 2020.

4. The medical disinfecting and sterilizing ultrasonic couplant of claim 1, wherein the dissolving agent is one or more selected from propylene glycol, glycerol and polyethylene glycol, and is preferably selected from propylene glycol and glycerol.

5. The medical disinfecting and sterilizing ultrasonic couplant of claim 1, wherein the neutralizing agent is selected from one or more of triethanolamine and sodium hydroxide.

6. A method for preparing the medical disinfecting and sterilizing type ultrasonic couplant as claimed in claim 1, wherein the method comprises the following steps:

1) taking 75-90% of the total amount of purified water, injecting the purified water into a container equipped with a stirring device, stirring at the normal temperature at the speed of 500-1000r/min, then adding the aqueous gel matrix, continuously stirring until the aqueous gel matrix is completely dispersed, heating to 65-80 ℃, keeping the temperature and stirring until the liquid is transparent, and cooling to 40 ℃ to obtain a gel;

2) dissolving a bactericide in a dissolving agent to prepare a solution 1;

3) adding the neutralizing agent into the rest purified water, stirring and cooling to normal temperature to obtain a solution 2;

4) slowly adding the solution 1 obtained in the step (2) and the solution 2 obtained in the step (3) into the gel obtained in the step (1), and uniformly stirring at the rotating speed of 20-40r/min while avoiding generating bubbles, thereby obtaining the medical disinfection sterilization type ultrasonic coupling agent.

7. Use of a compound of formula (I) or a pharmaceutically acceptable salt thereof, for the preparation of a bactericide:

8. use of a compound of formula (I) or a pharmaceutically acceptable salt thereof, for preparing a medical disinfecting and sterilizing ultrasound couplant:

Technical Field

The invention belongs to the technical field of medical ultrasonic imaging agents, and relates to a medical disinfection sterilization type ultrasonic coupling agent.

Background

The medical ultrasonic couplant is a sound-transmitting medium widely applied to medical ultrasonic diagnosis and treatment at present, and has the functions of strengthening the coupling between an ultrasonic probe and the skin of a human body, isolating the air between the ultrasonic probe and the skin of a detected part, and enabling the conduction of sound waves to be not attenuated by the influence of the air so as to achieve accurate and clear detection results.

The ultrasonic diagnosis and treatment used in hospitals are applied to various departments at present, such as common gynecological vaginal ultrasonography; performing two-dimensional and three-dimensional B-ultrasonic examination on a fetus; ultrasonic examination of urinary system and cardiovascular system. When used for ultrasonic diagnosis and treatment, the ultrasonic probe is often applied to different patient individuals and ultrasonic probes; therefore, these probes or repeatedly used medical ultrasound couplants inevitably carry some pathogenic bacteria or fungi. The current medical ultrasonic couplant is generally added with a bactericide for sterilization so as to achieve the purpose of reducing cross infection.

As the bactericide, chlorhexidine hydrochloride, poly-hexamethylene biguanide hydrochloride, triclosan and the like are commonly used at present, but a coupling agent containing such a bactericide has problems of high cytotoxicity, high skin irritation and the like. More importantly, the same bactericide has been used for a long time to make bacterial fungi prone to generate drug resistance, so that the need of providing a novel bactericide in the disinfection sterilization type ultrasonic couplant is urgent.

A compound (5- [1- (3, 4-dihydroxy-phenyl) -ethyl ] -cyclopenta [ c ] pyran-7-carbaldehyde) represented by the following formula (I) is a compound extracted from the fruit of Adansonia digita, which is reported in patent CN201610045677.6 and reported to have an antitumor effect:

the application discovers the function of the compound in the aspect of sterilization, and further applies the compound to the sterilization type ultrasonic couplant, thereby providing more choices for the sterilization type ultrasonic couplant.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a medical disinfection sterilization type ultrasonic coupling agent so as to provide excellent disinfection sterilization performance on the basis of providing a good ultrasonic coupling function.

In order to achieve the above object, the present invention provides the following technical solutions.

According to one aspect of the invention, the invention provides a medical disinfection sterilization type ultrasonic couplant, which comprises:

wherein the bactericide is a compound of the following formula (I) or a pharmaceutically acceptable salt thereof:

according to another aspect of the invention, the invention provides a method for preparing the medical disinfection sterilization type ultrasonic couplant, which comprises the following steps:

1) taking 75-90% of the total amount of purified water, injecting the purified water into a container equipped with a stirring device, stirring at the normal temperature at the speed of 500-1000r/min, then adding the aqueous gel matrix, continuously stirring until the aqueous gel matrix is completely dispersed, heating to 65-80 ℃, keeping the temperature and stirring until the liquid is transparent, and cooling to 40 ℃ to obtain a gel;

2) dissolving a bactericide in a dissolving agent to prepare a solution 1;

3) adding the neutralizing agent into the rest purified water, stirring and cooling to normal temperature to obtain a solution 2;

4) slowly adding the solution 1 obtained in the step (2) and the solution 2 obtained in the step (3) into the gel obtained in the step (1), and uniformly stirring at the rotating speed of 20-40r/min while avoiding generating bubbles, thereby obtaining the medical disinfection sterilization type ultrasonic coupling agent.

According to a further aspect of the invention, there is provided the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a fungicide.

According to another aspect of the invention, the invention also provides the application of the compound of formula (I) or the pharmaceutically acceptable salt thereof in preparing medical disinfection sterilization type ultrasonic couplant.

Has the advantages that:

the invention discovers the function of the compound shown in the formula (I) in the aspect of sterilization, and further applies the compound to the sterilization type ultrasonic couplant, thereby providing more choices for the sterilization type ultrasonic couplant. The test result shows that the compound in the formula (I) has an outstanding sterilization effect, so that the sterilization and disinfection type ultrasonic couplant can only contain a low-concentration bactericide, and realizes good sterilization and bacteriostasis effects. In addition, the medical disinfection sterilization type ultrasonic coupling agent meets the national standard, has no stimulation, sensitization and cytotoxicity of 0 grade on skin mucosa, is suitable for being used in various ultrasonic environments, and is particularly suitable for being used in occasions requiring high sterile conditions, such as operations, burns and scalds, natural body cavities and the like.

Detailed Description

Hereinafter, the present invention will be described in detail.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications mentioned in this application are herein incorporated by reference.

The invention provides a medical disinfection sterilization type ultrasonic coupling agent, which comprises:

wherein the bactericide is a compound of the following formula (I) or a pharmaceutically acceptable salt thereof:

the pharmaceutically acceptable salts of the compounds of formula (I) of the present invention are salts derived from various organic and inorganic counterions well known in the art.

In some embodiments of the medical disinfecting and sterilizing ultrasound couplant of the present invention, the aqueous gel matrix is selected from one or more of carbomer, hydroxyethyl cellulose, hydroxypropyl cellulose and sodium carboxymethyl cellulose, preferably carbomer.

In some embodiments of the medical disinfecting and sterilizing ultrasound couplant of the present invention, the carbomer is selected from one or more of carbomer 940, carbomer 941, carbomer 1342 or carbomer 2020.

In some embodiments of the medical disinfecting and sterilizing type ultrasonic couplant of the present invention, the dissolving agent is selected from one or more of propylene glycol, glycerol and polyethylene glycol, preferably propylene glycol and glycerol.

In some embodiments of the medical disinfecting and sterilizing ultrasonic couplant of the present invention, the neutralizing agent is selected from one or more of triethanolamine and sodium hydroxide.

In some embodiments of the medical disinfecting and sterilizing type ultrasonic couplant of the present invention, the couplant comprises 0.01-0.15%, such as 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.11%, 0.12%, 0.13%, 0.14% of a bactericide, based on the total weight.

In some embodiments of the medical disinfecting and sterilizing ultrasonic couplant of the present invention, the couplant comprises 0.5-1.5%, such as 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4% of the aqueous gel matrix by total weight.

In some embodiments of the medical disinfecting and sterilizing type ultrasonic couplant of the present invention, the couplant comprises 3.0-20.0%, for example, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 11.0%, 12.0%, 13.0%, 14.0%, 15.0%, 16.0%, 17.0%, 18.0%, 19.0% of the dissolving agent by total weight.

In some embodiments of the medical disinfecting and sterilizing type ultrasonic couplant of the present invention, the couplant comprises 0.1-3.0% by total weight of neutralizing agent, such as 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%.

According to another aspect of the invention, the invention provides a method for preparing the medical disinfection sterilization type ultrasonic couplant, which comprises the following steps:

1) taking 75-90% of the total amount of purified water, injecting the purified water into a container equipped with a stirring device, stirring at the normal temperature at the speed of 500-1000r/min, then adding the aqueous gel matrix, continuously stirring until the aqueous gel matrix is completely dispersed, heating to 65-80 ℃, keeping the temperature and stirring until the liquid is transparent, and cooling to 40 ℃ to obtain a gel;

2) dissolving a bactericide in a dissolving agent to prepare a solution 1;

3) adding the neutralizing agent into the rest purified water, stirring and cooling to normal temperature to obtain a solution 2;

4) slowly adding the solution 1 obtained in the step (2) and the solution 2 obtained in the step (3) into the gel obtained in the step (1), and uniformly stirring at the rotating speed of 20-40r/min while avoiding generating bubbles, thereby obtaining the medical disinfection sterilization type ultrasonic coupling agent.

According to a further aspect of the invention, there is provided the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a fungicide.

According to another aspect of the invention, the invention also provides the application of the compound of formula (I) or the pharmaceutically acceptable salt thereof in preparing medical disinfection sterilization type ultrasonic couplant.

Practical and presently preferred embodiments of the present invention are illustrated by the following examples.

However, it will be appreciated that those skilled in the art, on consideration of this disclosure, may make modifications and improvements within the spirit and scope of the present invention.