Medical ultrasonic coupling gel and preparation method thereof

Abstract

The invention provides a medical ultrasonic coupling gel and a preparation method thereof, and the medical ultrasonic coupling gel comprises the following components in parts by mass: 3.5-4.5 parts of probiotic microbubble powder; 8 to 12 parts of a surfactant; 6-8 parts of glycerol; 2.5 to 3.5 parts of sodium hyaluronate; 0.5 to 0.8 part of xanthan gum; 1.1 to 1.8 parts of a plant extract; 60 to 70 parts of deionized water; the probiotic microbubble powder comprises a gas core taking perfluorocarbon gas as a core, a shell material wrapping the gas core and probiotics loaded on the shell material. Probiotic microbubbles are introduced into ultrasonic coupling gel, dual functions of ultrasonic imaging quality improvement and skin micro-ecology regulation are coordinated, and meanwhile, in the ultrasonic inspection process, the probiotic microbubbles release active probiotics to regulate the skin micro-ecology under the action of body temperature and slight mechanical shearing of a probe.

Description

Technical Field

[0001] This invention relates to the field of medical technology, and more specifically to a medical ultrasound coupling gel and its preparation method. Background Technology

[0002] Medical ultrasound coupling agents are essential acoustic matching media between ultrasound probes and the skin. They are used to eliminate air gaps, achieve acoustic impedance matching, reduce ultrasound reflection loss, and provide lubrication. With the development of polymer materials science, gel-type coupling agents based on polymers such as carboxymethyl cellulose, polyethylene glycol, and carbomer have gradually become the mainstream.

[0003] However, with the widespread use of ultrasound examinations and the increasing frequency of probe reuse, the risk of cross-infection has become a significant challenge in clinical practice. As a high-frequency contact medical device, the surface of an ultrasound probe may harbor bacteria, fungi, and even viruses during continuous examinations of different patients. Ordinary coupling agents do not possess disinfection capabilities and may even cause secondary contamination due to repeated use. To address this issue, disinfectant-type ultrasound coupling agents have emerged, adding chemical disinfectants such as chlorotoluene and iodine to simultaneously disinfect the probe surface while achieving acoustic coupling. While existing disinfectant coupling agents reduce the risk of cross-infection to some extent, several technical bottlenecks remain: chemical disinfectants may irritate sensitive skin, some components may corrode and damage precision probes, and their antibacterial spectrum is often insufficient. For example, patent CN202110919564.5 discloses a disinfectant aerosol coupling agent that incorporates chemical bactericides such as trichlorohydroxydiphenyl ether and chlorhexidine gluconate, as well as plant extracts. While this enhances the disinfection effect, it carries risks of strong skin irritation, probe corrosion, and no enhancement effect on the ultrasound probe.

[0004] Therefore, further improvements and development are still needed. Summary of the Invention

[0005] To address the shortcomings of existing technologies and solve the aforementioned problems, a medical ultrasound coupling gel and its preparation method are proposed, and the following technical solution is provided: A medical ultrasound coupling gel, by weight, comprises the following components: 3.5-4.5 parts probiotic microbubble powder; 8-12 parts surfactant; 6-8 parts glycerin; 2.5-3.5 parts sodium hyaluronate; 0.5-0.8 parts xanthan gum; 1.1-1.8 parts plant extract; and 60-70 parts deionized water; wherein the probiotic microbubble powder comprises a gas core with perfluorocarbon gas as its core, a shell material encapsulating the gas core, and probiotics loaded on the shell material.

[0006] Furthermore, the particle size of the probiotic microbubble powder is 1-5 μm.

[0007] Furthermore, the mass ratio of the gas core, the shell material, and the probiotics is 1:15-20:2-3.

[0008] Furthermore, the shell material comprises a phospholipid monolayer formed by lecithin, a composite polysaccharide layer formed by chitosan and sodium alginate, and a protective outer layer formed by trehalose, with the probiotics loaded on the protective outer layer.

[0009] Furthermore, the mass ratio of lecithin, chitosan, sodium alginate and trehalose is 17-20:4.5-5.5:3.0-3.8:43-48.

[0010] Furthermore, the perfluorocarbon gas is perfluorohexane or perfluoropropane.

[0011] Furthermore, the mass ratio of perfluorocarbon gas, shell material, and probiotics is 1:15-25:2-3.

[0012] In addition, this application provides a method for preparing a medical ultrasound coupling gel, comprising the following steps: S1: Preparation of probiotic microbubble powder: Probiotics are dispersed in shell material raw materials, perfluorocarbon gas is introduced, and ultrasonic emulsification is performed to obtain microbubble suspension. The suspension is then freeze-dried to obtain probiotic microbubble powder. S2: Add glycerin, sodium hyaluronate, and xanthan gum to deionized water, mix and disperse to obtain the first mixture; S3: Add plant extract to the first mixture and stir to obtain a second mixture; S10: Add a surfactant to the second mixture to emulsify it and obtain a gel matrix; S11: The probiotic microbubble powder prepared in step S1 is added to the gel matrix at a temperature below 37°C. After stirring and sonication, the mixture is filtered to obtain the coupling gel.

[0013] Further, in step S1, probiotics are mixed with trehalose solution to prepare a bacterial suspension; lecithin, chitosan and sodium alginate are mixed in proportion, perfluorocarbon gas is introduced, ultrasonic emulsification is performed, and freeze-drying is carried out to obtain blank microbubble powder; the blank microbubble powder is added to the bacterial suspension, mixed and then freeze-dried again to obtain probiotic microbubble powder.

[0014] Furthermore, the probiotic microbubble powder mentioned in step S11 is added in three parts, and the process parameters of the ultrasound are: ultrasound frequency 40 kHz, power 140-160 W, and processing time 10-40 min.

[0015] Due to the adoption of the above technical solutions, the beneficial technical effects of the present invention are as follows: 1. This invention introduces probiotic microbubbles into an ultrasound coupling gel, achieving a dual synergistic effect of improving ultrasound imaging quality and regulating the skin's microecology. When ultrasound waves act on the coupling gel containing probiotic microbubbles, the microbubbles resonate and scatter, generating strong nonlinear echo signals, significantly enhancing the contrast and boundary clarity of the ultrasound image. Simultaneously, during ultrasound examination, the probiotic microbubbles release active probiotics under the influence of body temperature and the slight mechanical shearing action of the probe. These probiotics colonize the skin surface and metabolize to produce active substances such as lactic acid, bacteriocins, and short-chain fatty acids. Through a competitive inhibition mechanism, they repel common skin pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, maintaining the skin's microecological balance without disrupting normal flora and avoiding chemical irritation. This invention is particularly suitable for newborns and patients with sensitive skin.

[0016] 2. This invention also incorporates plant extracts, which work synergistically with probiotics to fight bacteria and inhibit bacterial growth. At the same time, it uses natural thickening systems xanthan gum and sodium hyaluronate to completely replace carbomer, further reducing skin irritation. Detailed Implementation

[0017] To enable those skilled in the art to better understand the technical solutions of the present invention, the technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Based on the embodiments in this application, other similar embodiments obtained by those skilled in the art without creative effort should all fall within the scope of protection of this application.

[0018] A medical ultrasound coupling gel, comprising the following components by weight: Probiotic microbubble powder 3.5-4.5 parts; surfactant 8-12 parts; glycerin 6-8 parts; sodium hyaluronate 2.5-3.5 parts; xanthan gum 0.5-0.8 parts; plant extract 1.1-1.8 parts; deionized water 60-70 parts; The probiotic microbubble powder comprises a gas core with perfluorocarbon gas as its core, a shell encapsulating the gas core, and probiotics loaded on the shell. This invention introduces probiotic microbubbles into an ultrasound coupling gel, achieving a dual synergistic effect of improved ultrasound imaging quality and regulation of the skin's microecology. Simultaneously, during ultrasound examination, the probiotic microbubbles release active probiotics to regulate the skin's microecology under the influence of body temperature and the slight mechanical shearing action of the probe.

[0019] In this invention, the probiotic is at least one of Lactobacillus rhamnosus and Bifidobacterium longum, with a viable count ≥ 1 × 10¹. 0 CFU / g.

[0020] The plant extracts are Coptis chinensis extract and green tea extract. The Coptis chinensis extract contains 50% berberine, and the green tea extract contains 40% EGCG.

[0021] Example 1 The recipe is as follows: Probiotic microbubble powder: 4.0 parts; Acidic sophorolipid: 10 parts; Glycerin: 7 parts; Sodium hyaluronate: 3.0 parts; Xanthan gum: 0.65 parts; Coptis chinensis extract: 0.7 parts; Green tea extract: 0.7 parts; Deionized water: 65 parts.

[0022] Probiotic microbubble composition ratio (mass ratio): Perfluorohexane:shell material:probiotics = 1:18:2.5 Shell material mass ratio: lecithin:chitosan:sodium alginate:trehalose = 18:5:3.4:45 Preparation steps: S1: Preparation of probiotic microbubble powder: Lactobacillus rhamnosus and Bifidobacterium longum were mixed with a 15% trehalose solution and stirred at 200 rpm at 8 degrees Celsius to prepare a solution with a viable count ≥1×10¹. 0 A bacterial suspension with CFU / g and a mass ratio of Lactobacillus rhamnosus to Bifidobacterium longum of 1:1 was prepared. Lecithin, chitosan, and sodium alginate were mixed in a specific ratio, and perfluorocarbon gas was introduced. The mixture was then ultrasonically emulsified using an ultrasonic emulsifier at a power of 300W for 10 minutes. The mixture was pre-frozen at -80℃ for 12 hours and then freeze-dried under vacuum for 48 hours to obtain blank microbubble powder. The blank microbubble powder was added to the bacterial suspension and mixed, then pre-frozen again at -80℃ for 12 hours and freeze-dried under vacuum for 48 hours to obtain probiotic microbubble powder. S2: Add glycerin, sodium hyaluronate and xanthan gum to deionized water, stir at 60°C for 30 min until completely transparent, to obtain the first mixture; S3: Add Coptis chinensis extract and green tea extract to the first mixture, and continue stirring at 50°C for 20 min to obtain the second mixture; S10: Add acidic sophorolipid to the second mixture and perform high-speed shear emulsification at 8000 rpm for 15 min to obtain a gel matrix; S11: The probiotic microbubble powder prepared in step S1 is divided into three equal parts by mass and added to the gel matrix in batches. After the first addition of probiotic microbubble powder at 30°C, it is sonicated for 10 minutes with an ultrasonic power of 150W. Then, the probiotic microbubble powder is added for the second time and sonicated for another 10 minutes with an ultrasonic power of 150W. Finally, the remaining probiotic microbubble powder is added and sonicated for another 10 minutes with an ultrasonic power of 150W. The mixture is then filtered to obtain the coupling gel.

[0023] Example 2 The recipe is as follows: Probiotic microbubble powder: 4.5 parts; Acidic sophorolipid: 10 parts; Glycerin: 7 parts; Sodium hyaluronate: 3.0 parts; Xanthan gum: 0.65 parts; Coptis chinensis extract: 0.7 parts; Green tea extract: 0.7 parts; Deionized water: 65 parts.

[0024] Microbubble component ratio (mass ratio): Perfluorohexane: Shell material: Probiotics = 1:20:3 Shell material mass ratio: lecithin:chitosan:sodium alginate:trehalose = 17:4.5:3:48 Preparation steps: S1: Preparation of probiotic microbubble powder: Lactobacillus rhamnosus and Bifidobacterium longum were mixed with a 15% trehalose solution and stirred at 200 rpm at 8 degrees Celsius to prepare a solution with a viable count ≥1×10¹. 0 A bacterial suspension with CFU / g and a mass ratio of Lactobacillus rhamnosus to Bifidobacterium longum of 1:1 was prepared. Lecithin, chitosan, and sodium alginate were mixed in a specific ratio, and perfluorocarbon gas was introduced. The mixture was then ultrasonically emulsified using an ultrasonic emulsifier at a power of 300W for 10 minutes. The mixture was pre-frozen at -80℃ for 12 hours and then freeze-dried under vacuum for 48 hours to obtain blank microbubble powder. The blank microbubble powder was added to the bacterial suspension and mixed, then pre-frozen again at -80℃ for 12 hours and freeze-dried under vacuum for 48 hours to obtain probiotic microbubble powder. S2: Add glycerin, sodium hyaluronate and xanthan gum to deionized water, stir at 60°C for 30 min until completely transparent, to obtain the first mixture; S3: Add Coptis chinensis extract and green tea extract to the first mixture, and continue stirring at 50°C for 20 min to obtain the second mixture; S10: Add acidic sophorolipid to the second mixture and perform high-speed shear emulsification at 8000 rpm for 15 min to obtain a gel matrix; S11: The probiotic microbubble powder prepared in step S1 is divided into three equal parts by mass and added to the gel matrix in batches. After the first addition of probiotic microbubble powder at 30°C, it is sonicated for 10 minutes with an ultrasonic power of 150W. Then, the probiotic microbubble powder is added for the second time and sonicated for another 10 minutes with an ultrasonic power of 150W. Finally, the remaining probiotic microbubble powder is added and sonicated for another 10 minutes with an ultrasonic power of 150W. The mixture is then filtered to obtain the coupling gel.

[0025] Example 3 The recipe is as follows: Probiotic microbubble powder: 3.5 parts; Acidic sophorolipid: 10 parts; Glycerin: 7 parts; Sodium hyaluronate: 3.0 parts; Xanthan gum: 0.65 parts; Coptis chinensis extract: 0.7 parts; Green tea extract: 0.7 parts; Deionized water: 65 parts.

[0026] Microbubble component ratio (mass ratio): Perfluorohexane: Shell material: Probiotics = 1:25:2 Shell material mass ratio: lecithin:chitosan:sodium alginate:trehalose = 20:5.5:3.8:43 Preparation steps: S1: Preparation of probiotic microbubble powder: Lactobacillus rhamnosus and Bifidobacterium longum were mixed with a 15% trehalose solution and stirred at 200 rpm at 8 degrees Celsius to prepare a solution with a viable count ≥1×10¹. 0 A bacterial suspension with CFU / g and a mass ratio of Lactobacillus rhamnosus to Bifidobacterium longum of 1:1 was prepared. Lecithin, chitosan, and sodium alginate were mixed in a specific ratio, and perfluorocarbon gas was introduced. The mixture was then ultrasonically emulsified using an ultrasonic emulsifier at a power of 300W for 10 minutes. The mixture was pre-frozen at -80℃ for 12 hours and then freeze-dried under vacuum for 48 hours to obtain blank microbubble powder. The blank microbubble powder was added to the bacterial suspension and mixed, then pre-frozen again at -80℃ for 12 hours and freeze-dried under vacuum for 48 hours to obtain probiotic microbubble powder. S2: Add glycerin, sodium hyaluronate and xanthan gum to deionized water, stir at 60°C for 30 min until completely transparent, to obtain the first mixture; S3: Add Coptis chinensis extract and green tea extract to the first mixture, and continue stirring at 50°C for 20 min to obtain the second mixture; S10: Add acidic sophorolipid to the second mixture and perform high-speed shear emulsification at 8000 rpm for 15 min to obtain a gel matrix; S11: The probiotic microbubble powder prepared in step S1 is divided into three equal parts by mass and added to the gel matrix in batches. After the first addition of probiotic microbubble powder at 30°C, it is sonicated for 10 minutes with an ultrasonic power of 150W. Then, the probiotic microbubble powder is added for the second time and sonicated for another 10 minutes with an ultrasonic power of 150W. Finally, the remaining probiotic microbubble powder is added and sonicated for another 10 minutes with an ultrasonic power of 150W. The mixture is then filtered to obtain the coupling gel.

[0027] Example 4 The recipe is as follows: Probiotic microbubble powder: 4.0 parts; Acidic sophorolipid: 12 parts; Glycerin: 8 parts; Sodium hyaluronate: 3.5 parts; Xanthan gum: 0.8 parts; Coptis chinensis extract: 0.9 parts; Green tea extract: 0.9 parts; Deionized water: 70 parts.

[0028] Microbubble component ratio (mass ratio): Perfluorohexane: Shell material: Probiotics = 1:18:2.5 Shell material mass ratio: lecithin:chitosan:sodium alginate:trehalose = 18:5:3.4:45 Preparation steps: S1: Preparation of probiotic microbubble powder: Lactobacillus rhamnosus and Bifidobacterium longum were mixed with a 15% trehalose solution and stirred at 200 rpm at 8 degrees Celsius to prepare a solution with a viable count ≥1×10¹. 0 A bacterial suspension with CFU / g and a mass ratio of Lactobacillus rhamnosus to Bifidobacterium longum of 1:1 was prepared. Lecithin, chitosan, and sodium alginate were mixed in a specific ratio, and perfluorocarbon gas was introduced. The mixture was then ultrasonically emulsified using an ultrasonic emulsifier at a power of 300W for 10 minutes. The mixture was pre-frozen at -80℃ for 12 hours and then freeze-dried under vacuum for 48 hours to obtain blank microbubble powder. The blank microbubble powder was added to the bacterial suspension and mixed, then pre-frozen again at -80℃ for 12 hours and freeze-dried under vacuum for 48 hours to obtain probiotic microbubble powder. S2: Add glycerin, sodium hyaluronate and xanthan gum to deionized water, stir at 60°C for 30 min until completely transparent, to obtain the first mixture; S3: Add Coptis chinensis extract and green tea extract to the first mixture, and continue stirring at 50°C for 20 min to obtain the second mixture; S10: Add acidic sophorolipid to the second mixture and perform high-speed shear emulsification at 8000 rpm for 15 min to obtain a gel matrix; S11: The probiotic microbubble powder prepared in step S1 is divided into three equal parts by mass and added to the gel matrix in batches. After the first addition of probiotic microbubble powder at 30°C, it is sonicated for 10 minutes with an ultrasonic power of 150W. Then, the probiotic microbubble powder is added for the second time and sonicated for another 10 minutes with an ultrasonic power of 150W. Finally, the remaining probiotic microbubble powder is added and sonicated for another 10 minutes with an ultrasonic power of 150W. The mixture is then filtered to obtain the coupling gel.

[0029] Example 5 The recipe is as follows: Probiotic microbubble powder: 4.0 parts; Acidic sophorolipid: 10 parts; Glycerin: 7 parts; Sodium hyaluronate: 3.0 parts; Xanthan gum: 0.65 parts; Coptis chinensis extract: 0.7 parts; Green tea extract: 0.7 parts; Deionized water: 65 parts.

[0030] Microbubble component ratio (mass ratio): Perfluorohexane: Shell material: Probiotics = 1:18:2.5 Shell material mass ratio: lecithin:chitosan:sodium alginate:trehalose = 18:5:3.4:45 Preparation steps: S1: Preparation of probiotic microbubble powder: Lactobacillus rhamnosus and Bifidobacterium longum were mixed with a 15% trehalose solution and stirred at 200 rpm at 8 degrees Celsius to prepare a solution with a viable count ≥1×10¹. 0A bacterial suspension with CFU / g and a mass ratio of Lactobacillus rhamnosus to Bifidobacterium longum of 1:1 was prepared. Lecithin, chitosan, and sodium alginate were mixed in a specific ratio, and perfluorocarbon gas was introduced. The mixture was then ultrasonically emulsified using an ultrasonic emulsifier at a power of 300W for 10 minutes. The mixture was pre-frozen at -80℃ for 12 hours and then freeze-dried under vacuum for 48 hours to obtain blank microbubble powder. The blank microbubble powder was added to the bacterial suspension and mixed, then pre-frozen again at -80℃ for 12 hours and freeze-dried under vacuum for 48 hours to obtain probiotic microbubble powder. S2: Add glycerin, sodium hyaluronate and xanthan gum to deionized water, stir at 60°C for 30 min until completely transparent, to obtain the first mixture; S3: Add Coptis chinensis extract and green tea extract to the first mixture, and continue stirring at 50°C for 20 min to obtain the second mixture; S10: Add acidic sophorolipid to the second mixture and perform high-speed shear emulsification at 8000 rpm for 15 min to obtain a gel matrix; S11: The probiotic microbubble powder prepared in step S1 is divided into three equal parts by mass and added to the gel matrix in batches. After adding the probiotic microbubble powder at 35°C, the mixture is sonicated for 30 minutes at an ultrasonic power of 150W. The mixture is then filtered to obtain the coupling gel.

[0031] Comparative Example 1 Compared to Example 1, no probiotic microbubble powder was added, but the rest of the process was the same as in Example 1.

[0032] Comparative Example 2 Compared to Example 1, no perfluorohexane or shell material was added, the probiotics were dispersed in the gel matrix, and the rest of the process was the same as in Example 1.

[0033] Comparative Example 3 Compared to Example 1, no probiotics were added, but the rest of the process was the same as in Example 1.

[0034] Comparative Example 4 The recipe is as follows: Microbubble powder: 4.0 parts; Acidic sophorolipid: 10 parts; Glycerin: 7 parts; Sodium hyaluronate: 3.0 parts; Xanthan gum: 0.65 parts; Coptis chinensis extract: 0.7 parts; Green tea extract: 0.7 parts; Deionized water: 65 parts; Lactobacillus rhamnosus: 0.23 parts; Bifidobacterium longum: 0.23 parts.

[0035] Microbubble component ratio (mass ratio): Perfluorohexane: Shell material = 1:18 Shell material mass ratio: lecithin:chitosan:sodium alginate:trehalose = 18:5:3.4:45 Preparation steps: S1: Preparation of microbubble powder: lecithin, chitosan, sodium alginate and trehalose are mixed in proportion, perfluorocarbon gas is introduced, and ultrasonic emulsification is performed using an ultrasonic emulsifier with a power of 300W for 10 minutes. The mixture is then pre-frozen at -80℃ for 12 hours and vacuum freeze-dried for 48 hours to obtain microbubble powder. S2: Add glycerin, sodium hyaluronate and xanthan gum to deionized water, stir at 60°C for 30 min until completely transparent, to obtain the first mixture; S3: Add Coptis chinensis extract and green tea extract to the first mixture, and continue stirring at 50°C for 20 min to obtain the second mixture; S10: Add acidic sophorolipid to the second mixture and perform high-speed shear emulsification at 8000 rpm for 15 min to obtain a gel matrix. Then add Lactobacillus rhamnosus and Bifidobacterium longum to the gel matrix and mix. S11: The microbubble powder prepared in step S1 is divided into three equal parts by mass and added to the gel matrix in batches. After the first addition of microbubble powder at 30°C, it is sonicated for 10 minutes with an ultrasonic power of 150W. Then, the microbubble powder is added for the second time and sonicated for another 10 minutes with an ultrasonic power of 150W. Finally, the remaining microbubble powder is added and sonicated for another 10 minutes with an ultrasonic power of 150W. The mixture is then filtered to obtain the coupling gel.

[0036] Comparative Example 5 Compared with Example 1, no Coptis chinensis extract and green tea extract were added, but the rest of the process was the same as in Example 1.

[0037] Comparative Example 6 Compared to Example 1, the probiotic microbubble powder was 1 part, and the other parts were the same as in Example 1.

[0038] The samples from Examples 1-5 and Comparative Examples 1-6 were subjected to relevant performance tests.

[0039] (1) Viscosity measurement A Brookfield DV2T rotational viscometer was used, with rotor No. 3 selected and rotation speed 12 rpm. The measurement was performed at 25℃±0.5℃. After the reading stabilized, the viscosity value (mPa·s) was recorded. The measurement was repeated three times and the average value was taken.

[0040] (2) Acoustic performance testing An ultrasonic velocity measuring instrument at a frequency of 5.0 MHz was used in a constant temperature water bath at 35℃. Sound velocity measurement: The time required for ultrasonic waves to travel a fixed distance in different samples is measured, and the sound velocity (m / s) is calculated.

[0041] Sound attenuation measurement: Measure the amplitude attenuation of ultrasonic waves before and after passing through different samples, and calculate the sound attenuation coefficient [dB / (cm·MHz)].

[0042] Imaging enhancement effect (relative amplitude): The relative echo amplitude of the sample was measured with the echo amplitude of pure water as a reference of 1.00. The higher the amplitude, the better the ultrasonic imaging enhancement effect.

[0043] (3) Antibacterial performance test - antibacterial loop method Indicator bacteria: Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 25922), Candida albicans (ATCC10231).

[0044] Operating steps: Preparation of indicator bacteria suspension (concentration approximately 1×10⁻⁶) 8 (CFU / mL).

[0045] Take 0.5 mL of bacterial suspension and spread it evenly on the surface of a nutrient agar plate.

[0046] Immerse a sterile filter paper (5 mm in diameter) into the sample, then remove it and attach it to the surface of the plate.

[0047] Incubate at 37℃ for 24 hours (for Candida albicans, incubate at 28℃ for 48 hours).

[0048] Measure the diameter of the inhibition zone (mm) and take the average of three measurements.

[0049] (4) Skin irritation test Refer to GB / T 16886.10-2017: Animals: Healthy New Zealand White rabbits (2.5-3.0kg), 3 per group.

[0050] operate: Hair was removed from both sides of the back 24 hours before the experiment, with one side being intact skin and the other being broken skin.

[0051] Apply 0.5g of sample to a 2.5cm x 2.5cm area, and cover with gauze and waterproof film.

[0052] After 4 hours of contact, the residue was removed, and erythema and edema reactions were observed at 1 hour, 24 hours, 48 ​​hours, and 72 hours after removal.

[0053] The stimulus index is calculated based on a standard scoring system.

[0054] (5) Stability test Accelerated aging: Place the sample in a constant temperature and humidity chamber at 40℃±2℃ and 75%±5% RH for 90 days.

[0055] Testing indicators: viscosity, pH value, and probiotic survival rate were tested at 0 days, 30 days, 60 days, and 90 days, respectively.

[0056] The viscosity and acoustic performance data are shown in Table 1 below.

[0057] Table 1. Results of viscosity and acoustic performance data As shown in the table above, the relative amplitudes of Examples 1-5 are significantly higher than the pure water baseline of 1.00, reaching 1.20-1.35. This indicates that probiotic microbubbles resonate and scatter in the ultrasonic field, generating strong nonlinear echo signals and enhancing imaging contrast. Among them, Example 2, with a probiotic microbubble content of 4.5 parts, has the highest relative amplitude of 1.35, while Example 3, with a probiotic microbubble content of 33.5 parts, has a relative amplitude of 1.20, showing a positive correlation between probiotic microbubble content and imaging enhancement effect. Comparative Example 1, without probiotic microbubbles, has a relative amplitude of only 0.95, lower than pure water, directly proving that microbubbles are the key to imaging enhancement. Comparative Example 2, without perfluorocarbon gas and shell material, has a relative amplitude of 1.02, slightly higher than water but much lower than Example 1, indicating that even with a small amount of probiotics and plant extracts, without microbubble structure, the resonance effect almost disappears. The relative amplitudes of Comparative Examples 3, 4, and 5 are close to those of Example 1 because they retain the microbubble structure.

[0058] Comparative Example 6 had a probiotic microbubble content of 1 part, with a relative amplitude of 1.15, which was lower than that of Example 1, further verifying the effect of content.

[0059] The antibacterial test results are shown in Table 2.

[0060] Table 2 Antibacterial test data results The survival rates of Examples 1-4 were all >80%, indicating that the effective load of probiotics effectively protected them from mechanical shearing and ultrasonic damage during the preparation process. In Comparative Example 2, where perfluorohexane and shell material were absent, the probiotics were directly dispersed in the gel matrix, resulting in a survival rate of only 38.5%, far lower than that of Example 1. This was because the probiotics were directly exposed to high-shear emulsification and ultrasonic treatment, leading to a large number of deaths.

[0061] In Comparative Example 4, the survival rate of microbubbles and probiotics was 41.2%, which was also very low. Although microbubble powder was present, the probiotics were not loaded and were directly added to the gel matrix. Subsequent ultrasonic treatment led to the death of the probiotics. This proves that the "loading structure" of microbubbles is a necessary condition for protecting the activity of probiotics. Comparative Example 5, without plant extracts, had a survival rate of 80.8%, which was lower than that of Example 1. Plant extracts can synergistically inhibit the bacteria with probiotics, and can also protect the probiotics from inactivation through antioxidation and stabilization. In Example 5, the probiotics were added at 35°C and ultrasonicated once, resulting in a survival rate of 79.5%, lower than that of Example 1. This indicates that process parameters such as temperature and ultrasonication method have a significant impact on the survival rate: batch addition and intermittent ultrasonication are better than continuous ultrasonication, and a low temperature of 30°C is better than 35°C. In addition, Example 1 showed a 12.5 mm inhibition zone against Staphylococcus aureus and a bactericidal rate of 96.5%, and also had good effects on Escherichia coli and Candida albicans. Comparative Example 1 maintained weak antibacterial activity solely through plant extracts, with an inhibition zone smaller than 7 mm, failing to meet the effective antibacterial standard. Comparative Example 2 showed a slightly higher antibacterial effect than Comparative Example 1, but still significantly lower than Example 1 due to low probiotic survival rate and insufficient activity. Comparative Example 3, without probiotics, exhibited an antibacterial effect between Comparative Example 1 and Example 1, indicating that the plant extracts themselves have some antibacterial activity, but the effect is greatly enhanced when combined with probiotics. Comparative Example 4 showed a similar antibacterial effect to Comparative Example 2, also influenced by low probiotic survival rate. Comparative Example 5 showed a significantly lower antibacterial effect than Example 1, but higher than Comparative Example 3, indicating that probiotics alone have some effect, but a synergistic effect occurs when combined with plant extracts, significantly improving antibacterial performance. Comparative Example 6 showed an antibacterial effect between Example 3 and Example 1, positively correlated with microbubble content.

[0062] The data on skin irritation and stability are shown in Table 3.

[0063] Table 2 Results of skin irritation and stability data In this embodiment, all samples had an irritation index of 0.0, reaching the "non-irritating" level. Comparative Example 1 had an irritation index of 0.2, also within the non-irritating range. This demonstrates that the xanthan gum + sodium hyaluronate natural thickening system used in this invention has excellent safety and completely replaces carbomer, which may cause irritation. Compared with traditional chemically disinfected coupling agents (which usually have slight irritation), this product has a significant advantage in terms of skin safety. Except for Example 5, which showed a viscosity change rate of <6% and a survival rate decrease of <11% after 90 days of accelerated aging, all other examples exhibited good shelf stability. Comparative Examples 2 and 4 showed a very severe decrease in survival rate because the probiotics were not effectively protected and died rapidly during the aging process. The 15.8% decrease in survival rate in Example 5 was related to the low initial survival rate.

[0064] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A medical ultrasound coupling gel, characterized in that, By weight, it includes the following components: 3.5-4.5 parts probiotic microbubble powder; 8-12 parts surfactant; 6-8 parts glycerin; 2.5-3.5 parts sodium hyaluronate; 0.5-0.8 parts xanthan gum; 1.1-1.8 parts plant extract; 60-70 parts deionized water; The probiotic microbubble powder includes a gas core with perfluorocarbon gas as its core, a shell material encapsulating the gas core, and probiotics loaded on the shell material.

2. The medical ultrasound coupling gel according to claim 1, characterized in that, The particle size of the probiotic microbubble powder is 1-5 μm.

3. The medical ultrasound coupling gel according to claim 1, characterized in that, The mass ratio of the gas core, the shell material, and the probiotics is 1:15-20:2-3.

4. The medical ultrasound coupling gel according to claim 1, characterized in that, The shell material comprises a phospholipid monolayer formed by lecithin, a complex polysaccharide layer formed by chitosan and sodium alginate, and a protective outer layer formed by trehalose, with the probiotics loaded on the protective outer layer.

5. The medical ultrasound coupling gel according to claim 4, characterized in that, The mass ratio of lecithin, chitosan, sodium alginate and trehalose is 17-20:4.5-5.5:3.0-3.8:43-48.

6. The medical ultrasound coupling gel according to claim 1, characterized in that, The perfluorocarbon gas is perfluorohexane or perfluoropropane.

7. The medical ultrasound coupling gel according to claim 1, characterized in that, The mass ratio of perfluorocarbon gas, shell material and probiotics is 1:15-25:2-3.

8. A method for preparing the medical ultrasound coupling gel as described in any one of claims 1-7, characterized in that, Includes the following steps: S1: Preparation of probiotic microbubble powder: Probiotics are dispersed in shell material raw materials, perfluorocarbon gas is introduced, and ultrasonic emulsification is performed to obtain microbubble suspension. The suspension is then freeze-dried to obtain probiotic microbubble powder. S2: Add glycerin, sodium hyaluronate, and xanthan gum to deionized water, mix and disperse to obtain the first mixture; S3: Add plant extract to the first mixture and stir to obtain a second mixture; S10: Add a surfactant to the second mixture to emulsify it and obtain a gel matrix; S11: The probiotic microbubble powder prepared in step S1 is added to the gel matrix at a temperature below 37°C. After stirring and sonication, the mixture is filtered to obtain the coupling gel.

9. The method for preparing the medical ultrasound coupling gel according to claim 8, characterized in that, In step S1, probiotics are mixed with trehalose solution to prepare a bacterial suspension; lecithin, chitosan and sodium alginate are mixed in proportion, perfluorocarbon gas is introduced, ultrasonic emulsification is performed, and freeze-drying is carried out to obtain blank microbubble powder; the blank microbubble powder is added to the bacterial suspension, mixed and then freeze-dried again to obtain probiotic microbubble powder.

10. The method for preparing the medical ultrasound coupling gel according to claim 9, characterized in that, The probiotic microbubble powder in step S11 is added in three parts, and the ultrasonic process parameters are: ultrasonic frequency 40 kHz, power 140-160 W, and processing time 10-40 min.

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