WO2007073643A1

WO2007073643A1 - Ultrasonic coupling agent and its preparation process and packaging container contg.same

Info

Publication number: WO2007073643A1
Application number: PCT/CN2006/001714
Authority: WO
Inventors: Yunbo Tian; Zhibiao Wang; Jin Bai
Original assignee: Chongqing Haifu (Hifu) Technology Co., Ltd.
Priority date: 2005-12-28
Filing date: 2006-07-17
Publication date: 2007-07-05
Also published as: CN1990048B; CN1990048A

Abstract

Ultrasonic coupling agent comprises(by weight)0.5-10% carbopol, 74-983% solvent, 0.1-2% metronidazole,0.5-10% humectant,0.1-2% antibiotic,0.1-2% anesthetic. The coupling agent is prepared by (1)providing said components, (2)mixing homogeneously or dissolving,(3)adjusting the pH to 5.5-8.0,(4)mixing homogeneously through stirring, and (5) sterilizing by deaerating tank. The packaging container consists of container and tube. Said tube has a blunt front end, and said container is in pumping bottle or syringe form. The coupling agent has a controlled viscosity. It is safe and stable, can be used in ultrasonic investigation without causing burn of skin and can kill bacteria and prevent cross infection, and allows easy sliding of the transducer on the skin.

Description

Ultrasonic therapeutic coupling agent, preparation method thereof and packaging device

The invention belongs to the technical field of ultrasonic treatment, and particularly relates to an ultrasonic therapeutic coupling agent, a preparation method thereof and a packaging device. Background technique

In the field of ultrasonic therapy technology, the couplant is a substance that is coupled between the ultrasonic head and the skin to facilitate filling of voids and to prevent interfacial reflection by air layer, so as to facilitate the passage of ultrasonic energy (Feng Ruo, Wang Zhiwei, editor-in-chief) Therapeutics. 1st edition, Beijing, Science and Technology Literature Publishing House. 2002; 11: 206).

In the current ultrasound treatment, common couplants (such as castor oil, liquid paraffin, glycerin and petrolatum) and distilled water are commonly used in the coupling agent.

Ordinary couplants are basically packaged in large capacity, and cannot be single-sterilized. After ultrasound treatment, the permeability of tissue cells tends to increase, and the ability to resist microbial attack is weakened. If the coupling agent itself is contaminated with no bacteriostatic and bactericidal ingredients, it can easily lead to tissue infection after treatment. At the same time, most of the common ultrasonic coupling agents used hydrogels have good viscosity performance at rest, but in ultrasonic therapy, the viscosity of the coupling agent applied between the end surface of the treatment head and the surface of the treatment area is due to the ultrasonic treatment head. The reciprocating movement is significantly reduced, causing the couplant to be lost on the non-horizontal treatment surface, resulting in a decrease in coupling effect and a decrease in lubrication performance. The friction between the ultrasonic treatment head and the contact surface is also increased, not only for the doctor. The inconvenience of the treatment operation also increases the risk of rubbing on the treated surface; since the therapeutic ultrasound energy does not pass well through the surface of the treatment area, there is a risk of burns on the surface of the treatment area. In addition, due to therapeutic ultrasound, especially focused ultrasound inevitably stimulates the subcutaneous nerve to produce pain, but ordinary ultrasound coupling The agent has no analgesic effect. Moreover, the viscosity also changes at different ambient temperatures. When distilled water is used as the ultrasonic coupling agent, it is generally used in two cases. One is to immerse the treatment surface and the treatment head in distilled water. This coupling method works well, but it is not easy to implement in general treatment. The second is to maintain coupling by using distilled water between the ultrasound treatment head and the treatment surface, but because the treatment surface is often not horizontal, such as treatment of some gynecological diseases, such as leukoplakia, chronic cervicitis, etc., due to these diseases The anatomical position can only spray distilled water directly in the target area, and the distilled water has poor viscosity and easy to flow around. It requires a large amount of running water to fill and can not couple the ultrasonic head and the treatment surface well, thus causing pollution to the operating environment. It brings a lot of inconvenience to doctors and patients, and it has no painkilling effect.

SUMMARY OF THE INVENTION The technical problem to be solved by the present invention is to provide a good acoustic performance, stability, safety, and the ability to maintain the reciprocating motion of the treatment head and at different ambient temperatures in view of the deficiencies of the prior art ultrasonic coupling agent. Ultrasonic therapeutic coupling agent requiring viscosity, antibacterial and analgesic effect, preparation method thereof, packaging method and application. The technical solution adopted to solve the technical problem of the present invention is that the ultrasonic coupling agent contains the following components by weight:

Carbomer 0.5-10%

Solvent 74~98.7%;

Further, the ultrasonic coupling agent of the present invention further comprises:

Metronidazole 0.1-2%

Humectant 0.5~10% _;

Antibiotic drugs 0.1~2% _;

Anesthetic drug 0.1~2% The function of the humectant is to maintain a sufficient water content in the coupling agent; metronidazole is a white or milky white crystalline powder, the product has anti-anaerobic effect, strong killing of trichomoniasis, can reduce or avoid surgical infection; The agent is selected from the group consisting of polyhydric alcohols such as polyethylene glycol (PEG), glycerin, propylene glycol, preferably medicinal polyethylene glycol (PEG); the antibiotic drugs are macrolide-like antibiotics such as spiramycin, clarithromycin The anesthetic is an amide or ester local anesthetic such as procaine, bupivacaine and lidocaine, and the solvent is distilled water. Carbomer's chemical name: cross-linked polyacrylic acid resin, molecular structure: - [-CH2-CH-]n-COOH.

The preparation method of the above ultrasonic coupling agent specifically includes the following steps:

(1) Weigh the components by weight:

Carbomer 0.5-10%

Solvent 74~98.7%

(2) mixing or dissolving the components: taking carbomer to swell in the solvent;

(3) Adjust the PH value to 5.5~8.0;

(4) Degassing cans for disinfection. The carbomer in step (2) can be swollen in the solvent by heating or changing the pH (such as adding NaOH). Step (1) further comprises weighing 0.1~2% of metronidazole, 0.5-10% of humectant, 0.1~2% of antibiotic drug, and step (2) swelling carbomer to dissolved methotrexate In the solvent of the azole, the antibiotic drug and the humectant are added to the solution of the step (2) and stirred uniformly. Further, the antibiotic drug is first dissolved in the humectant, and then added to the solution of the step (2) and stirred uniformly. The step (1) further includes weighing 0.1 to 2% of the anesthetic, adding the anesthetic to the solution of the step (2) or the solution of the step (2) and the mixture of the antibiotic and the moisturizer. As described in the above preparation method, the solvent is distilled water, and metronidazole is a white or milky white crystalline powder. Antibiotic drugs use macrolide antibiotics, humectants use polyols, and anesthetics use amide or ester local anesthetics. The carbomer is swollen in distilled water and heated to 70 辅 in a water bath to accelerate the swelling process. The solid tablets of the macrolide antibiotics are ground into fine powder and dissolved in polyethylene glycol, fully stirred and dissolved, and then filtered. Mix the filtrate with the dissolved carbomer and mix well. Add the anesthetic and mix well. Adjust the enthalpy to 5.5 8.0. Stir well.

In the above preparation method, the carbomer can be swollen in the solvent by heating or changing the enthalpy (for example, using NaOH); when deaerating, the vacuum or centrifugal degassing can be used.

Fully or controlled de-airing.

In the above preparation method, the antibiotic drug can be uniformly dispersed in the couplant and stabilized by a special treatment method (that is, the drug is dispersed and dissolved in a humectant by means of an ultrasonic pulverizer and then subjected to high pressure filtration).

The ultrasonic coupling agent prepared according to the above method may be additionally added with an auxiliary material as needed.

The resulting ultrasonic couplant is used for convenient and safe use. The present invention also provides a package container for an ultrasonic couplant, the device comprising a container for the ultrasonic couplant, the container being provided with a single sterilized, separately packaged catheter. Since the catheter is in direct contact with the skin or mucosal surface, the front end of the catheter is blunt in order to protect the skin or mucosal surface. A preferred container for the ultrasonic coupling agent can be a spring bottle or a syringe.

The ultrasonic coupling agent provided by the invention has the advantages of good carbomer thickening effect, strong shear resistance and permanent stability at high viscosity, and polyethylene glycol (PEG) can be used as a moisturizer, and Dissolves the action of the active ingredients of antibiotics. In the treatment, the invention can make the treatment head move smoothly, has sufficient coupling, reduces the pain and discomfort of the treatment, has a clean treatment surface, and has anti-infection effect after treatment, and can be widely applied to ultrasonic treatment, especially for leukoplakia and chronic diseases. Diseases such as cervicitis can play a good coupling role.

For the present invention, an ultrasonic treatment coupling agent, observed by physical detection and animal efficacy experiments The effect of ultrasound treatment on animals. The results show that the couplant has a sound velocity of 1520 ~ 1620m / s at 35 ° C _; acoustic impedance (1.5 ~ 1.7) X 10 ⁶ Pa · s / m; sound attenuation coefficient 0.05dB / (cm · MHz); Viscosity (25 ° C): 15 ~ 80Pa / s; PH: 5.5 ~ 8. Apply directly to rabbit eyes and no irritating or toxic side effects were observed.

The ultrasonic coupling agent of the invention adopts the synthetic high-molecular substance carbomer as a matrix, adds antibiotic drugs by a special drug dissolution method, controls the viscosity of the proper coupling agent, and applies the unique packaging disinfection method to the ultrasonic treatment, which is safe and stable. , the advantages of good acoustic performance. Ultrasound treatment with this couplant can effectively avoid skin burns caused by the couplant itself. The ultrasonic treatment head moves smoothly, the coupling is sufficient, the treatment surface is clean, the anti-infection effect after treatment, and the raw materials are abundant. The cost is low, the production process is simple, hygienic and safe, and the packaging is easy to use. In the course of ultrasound treatment of gynecological diseases, the ultrasonic therapeutic couplant of the present invention can be a suitable coupling medium.

The matrix of the present invention, carbomer, can be varied in concentration depending on the temperature of the use environment, resulting in a consistent viscosity performance at various ambient temperatures. DRAWINGS

Figure 1 is a schematic view of a package of an ultrasonic coupling agent of the present invention

2 is another packaging diagram of the ultrasonic coupling agent of the present invention

In the figure: 〗 A catheter 2 - bottle body 3 - cylinder 4 a spring body 5 - container tube 6 - push handle

The content of the present invention will be further described in detail below with reference to the embodiments and the accompanying drawings. Example 1

The ultrasonic coupling agent of this embodiment is composed of the following weight percentages: carbomer 0.5%, metronidazole 0.1%, Polyethylene glycol 0.5%, spiramycin 0.1% procaine 0.1%, distilled water 98.7%.

Preparation method: Take carbomer to swell in distilled water which has dissolved metronidazole, and simultaneously heat it to 70 °C in water bath to accelerate the swelling process; take the spiromycin solid tablet into fine powder and dissolve it in the polymer by ultrasonic pulverizer In the ethylene glycol, fully stirred and dissolved, and then filtered under high pressure. The filtrate is mixed with the dissolved carbomer and stirred evenly. Then add procaine. Adjust the pH value to 5.5 8.0 with NaOH during the mixing process, and mix well; The tank can be degassed by centrifugal degassing after being filled in a pneumatic tank. The gas content can be controlled by the time and speed of centrifugation, and generally no fine bubbles can be seen by the naked eye. At this point, the preparation process is completed. The ultrasonic coupling agent prepared in this embodiment is nearly transparent and water-soluble, and contains only or no gel which is invisible to the naked eye and is incapable of detecting microbubbles and insoluble foreign substances. Suitable for winter or below 10 °C. The effects of ultrasonic treatment on animals were observed by physical test and animal efficacy test. The results showed that the technical performance index of the couplant was 35 Ό, the sound performance was: 1520 ~ 1620 m / s; Impedance (1.5~1.7) X 10 ⁶ Pa - s/m; Sound attenuation coefficient 0.05dB/(cm · MHz); Viscosity (25.C): 15~ 80Pa/s; PH: 5.5~8. Apply directly to rabbit eyes without irritating or toxic side effects.

Packing: As shown in Fig. 1, the ultrasonic couplant packaging container comprises a bottle body 2 and a catheter 1. The bottle body has a spring body 4, and the catheter 1 is disposed at the front end of the bottle body. The material of the catheter 1 is non-toxic. A flexible hose that retains its original shape. The length is 8~15cm, the front end is blunt, and it can directly contact the skin or mucous membrane surface. It is a single-use, sterilized and individually packaged catheter.

The ultrasonic coupling agent prepared in this embodiment is filled in the disposable spring bottle body and used after being sterilized by radiation. Example 2:

The ultrasonic coupling agent of the present embodiment is composed of the following weight ratio: carbomer 10%, metronidazole 2%, Polyethylene glycol 10%, clarithromycin 2%, bupivacaine 2%, distilled water 74%.

Preparation method: Take carbomer to swell in distilled water which has dissolved metronidazole, and heat it to 70 °C with water bath to accelerate the swelling process; take clarithromycin solid tablets into fine powder and dissolve in polyethylene glycol , thoroughly stir and dissolve, filter, take the filtrate and mix with the dissolved carbomer and mix well, then add bupivacaine to mix, adjust the PH value to 5.5~8.0, fully stir evenly; use the canned air tank after canning Centrifugal degassing is used to degas, and the gas content in the centrifuge can be controlled by the time and speed of centrifugation. Generally, fine bubbles are not visible to the naked eye. At this point, the preparation process is completed. The ultrasonic coupling agent prepared in this embodiment is nearly transparent and water-soluble, and contains only or no gel which is invisible to the naked eye and is incapable of detecting microbubbles and insoluble foreign substances. Suitable for summer or above 30 °C. The effects of ultrasound treatment on animals were observed by physical testing and animal efficacy experiments. The results show that the couplant at 35 ° C, its technical performance index is within the range: Sound velocity: 1520 ~ 1620m / s; acoustic impedance (1.5 1.7) X 10 ⁶ Pa · s / m _; sound attenuation Coefficient 0.05dB/(cm · fflz); Viscosity (25°C): 15 ~ 80Pa/s _; PH: 5.5~8. Apply directly to rabbit eyes and no irritating or toxic side effects were observed.

Packing: As shown in Fig. 2, the ultrasonic couplant packaging container comprises a cylinder 3, a conduit 1, the cylinder 3 is a syringe container, the front part is a container cylinder 5, the rear part is a push handle 6, and the duct 1 is arranged in a container cylinder The front end of the 5, the material of the catheter 1 is non-toxic, and the flexible hose can maintain the original shape. The catheter material is a non-toxic, flexible hose that retains its original shape. It is 8~15cm long and has a rounded front end. It can directly contact the skin or mucous membrane surface. It is a disposable, individually packaged catheter.

The ultrasonic coupling agent prepared in this embodiment is filled in the above-mentioned disposable syringe type container and used after being sterilized by radiation.

Example 3:

The ultrasonic coupling agent of this embodiment is composed of the following weight percentages: carbomer 5%, metronidazole 1%, poly 5% of ethylene glycol, 1% of macrolide antibiotics, 1% of anesthetics, and 87% of distilled water.

Preparation method: taking carbomer swelled in distilled water which has dissolved metronidazole, and simultaneously heated to 70 in a water bath to accelerate the swelling process; taking the solid tablets of medimycin into fine powder and dissolving in polyethylene glycol, After thoroughly stirring and dissolving, filter, take the filtrate and mix with the dissolved carbomer and mix well, then add lidocaine to mix, adjust the PH value to 5.5 8.0, stir well; use the pneumatic canning method to use the centrifugal degassing after centrifugation In the manner of degassing, the gas content in the centrifuge can be controlled by the time and rotation speed of the centrifugation, and generally no fine bubbles can be seen by the naked eye. At this point, the preparation process is completed. The ultrasonic coupling agent prepared in this embodiment is nearly transparent and water-soluble, and contains only or no microbubbles which are not easily noticeable to the naked eye, and gels which have no insoluble foreign matter. Suitable for spring and autumn or 10~30 °C environment. The effects of ultrasound treatment on animals were observed by physical testing and animal efficacy experiments. The results show that the couplant at 35 ° C, its technical performance index is within the range: sound speed: 1520 ~ 1620m / s; acoustic impedance rate (1.5 ~ 1.7) X 10 ⁶ Pa · s / m _; Attenuation coefficient 0.05dB / (cm · 匪z); viscosity (25 ° C): 15 ~ 80Pa / s _; PH: 5.5 ~ 8. Apply directly to rabbit eyes without irritation or side effects.

Packing: As shown in Fig. 2, the ultrasonic couplant packaging container comprises a cylinder 3, a conduit 1, the cylinder 3 is a syringe container, the front part is a container cylinder ₅ , the rear part is a push handle ₆ , and the duct 1 is arranged in a container cylinder The front end of the 5, the material of the catheter 1 is non-toxic, and the flexible hose can maintain the original shape. The catheter material is non-toxic, flexible hose that can maintain the original shape, the length is 8 ~ 15cm, the front end is blunt, can directly contact the skin or mucous membrane surface, and is a single-time disinfected and individually packaged catheter.

Claims

Claim

An ultrasonic coupling agent characterized by comprising the following weight percentage components:

Carbomer 0.5-10%

Solvent 74~98.7%

2. The ultrasonic coupling agent according to claim 1, which further comprises 0.1 to 2% of metronidazole.

3. The ultrasonic coupling agent according to claim 1, which further comprises 0.5 to 10% of a humectant.

4. The ultrasonic coupling agent according to claim 3, wherein the humectant is selected from the group consisting of polyols.

The ultrasonic coupling agent according to claim 4, wherein the polyol is medicinal polyethylene glycol (PEG).

The ultrasonic coupling agent according to any one of claims 1 to 5, which further comprises 0.1 to 2% of an antibiotic drug.

The ultrasonic coupling agent according to claim 6, wherein the antibiotic drug is an antibiotic such as a macrolide.

8. The ultrasonic coupling agent according to claim 6, further comprising 0.1 to 2% of an anesthetic.

The ultrasonic coupling agent according to claim 8, wherein the anesthetic is an amide local anesthetic.

The ultrasonic coupling agent according to any one of claims 1 to 5, characterized in that the solvent is distilled water.

11. A method of preparing an ultrasonic coupling agent, comprising the following steps:

(1) Weigh the components by weight - Carbomer 0.5-5%

Solvent 81~98.8%

(3) Adjust the PH value to 5.5~8.0;

(4) Degassing cans for disinfection.

A method of preparing an ultrasonic coupling agent according to claim 11, wherein the carbomer in the step (2) is swellable in a solvent by heating or changing the pH.

The method for preparing an ultrasonic coupling agent according to claim 11, wherein the step (1) further comprises: weighing 0.1 to 2% of metronidazole, 0.5 to 10% of a moisturizing agent, and 0.1 to 2% of the In the antibiotic drug, in step (2), the carbomer is swollen in a solvent in which the metronidazole has been dissolved, and the antibiotic drug and the humectant are added to the solution in the step (2) and stirred uniformly.

The method for preparing an ultrasonic coupling agent according to claim 13, wherein the antibiotic drug is first dissolved in the moisturizer, and then added to the step (2) to be uniformly stirred.

The method for preparing an ultrasonic coupling agent according to claim 11 or 13 or 14, wherein the step (1) further comprises: weighing 0.1 to 2% of the anesthetic drug, and adding the anesthetic drug to the step (2) The solution in solution or step (2) is added to a mixture of metronidazole, antibiotics and humectants.

16. A method of preparing an ultrasonic coupling agent according to claim 13, wherein the solvent is distilled Water, metronidazole is white or milky white crystalline powder, antibiotic drugs use macrolide antibiotics, humectants select polyol polyethylene glycol, carbomer swells in distilled water containing dissolved metronidazole At the same time, it is heated to 70 °C by water bath to accelerate the swelling process. The solid tablets of macrolide antibiotics are ground into fine powder and dissolved in polyethylene glycol. After thorough stirring and dissolution, the filtrate is taken and the dissolved card is taken. Bloom the mixture evenly, then add the anesthetic to mix, adjust the pH to 5.5 8.0, and mix well.

The method for preparing an ultrasonic coupling agent according to claim 11, characterized in that in the step (5), when the bubble is removed, the bubble can be completely or controlled by means of vacuum or centrifugal degassing.

18, an ultrasonic couplant packaging container, comprising a bottle body 2, a catheter 1, characterized in that the bottle body has a section of the spring body 4, the catheter 1 is disposed at the front end of the bottle body, the material of the catheter 1 is non-toxic, A flexible hose that retains its original shape.

19. An ultrasonic couplant packaging container comprising a barrel 3 and a catheter 1, wherein the barrel 3 is a syringe type container, the front part is a container barrel 5, the rear part is a push handle 6, and the tube 1 is disposed in the container barrel 5. The front end of the catheter 1 is a non-toxic, flexible hose that retains its original shape.

The ultrasonic couplant packaging container according to claim 18 or 19, wherein the catheter 1 is 8 cm to 15 cm long and has a rounded front end, and is a single-use sterilized individually packaged catheter.