Tanba gastrointestinal ultrasound contrast agent as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of ultrasonic contrast agents, and discloses a tsamba gastrointestinal ultrasonic contrast agent as well as a preparation method and application thereof. The contrast agent takes Tibet Plateau pure natural tsamba powder as a core matrix, is subjected to superfine grinding and sterilization, is matched with a natural suspension stabilizer, a food-grade defoaming agent and a flavoring agent, and is blended with warm water according to a specific proportion to form a suspension; the preparation process comprises three steps of raw material pretreatment, dry mixing and suspension preparation, and is simple and convenient to operate. By regulating and controlling parameters such as granularity (more than 90% of particles are 10-50 microns) and concentration (8-12g / 100mL warm water) of zanba powder, acoustic characteristics can be adjusted, in-vitro detection shows that the contrast agent is medium-fine in echo, stable in suspension within 30 minutes and free of rear sound attenuation, and a gastrointestinal wall structure can be clearly drawn. The invention has the advantages of high biocompatibility, low side effect, good patient tolerance, nutrition support effect, convenience in storage and transportation and low preparation cost, and is suitable for gastrointestinal ultrasound examination of various crowds.

Description

Technical Field

[0001] This invention belongs to the field of ultrasound contrast agent technology, specifically relating to a tsampa gastrointestinal ultrasound contrast agent, its preparation method, and its application. Background Technology

[0002] Gastrointestinal ultrasound contrast imaging is a non-invasive diagnostic method for gastrointestinal diseases, and the performance of the contrast agent directly determines the accuracy of the examination results. Currently available gastrointestinal ultrasound contrast agents are mostly chemically synthesized preparations or ordinary cereal pastes. Chemically synthesized preparations have problems such as poor biocompatibility, easy to cause bloating, and obvious odor, resulting in low patient tolerance, and are especially unsuitable for children and people with sensitive constitutions. Ordinary cereal pastes (such as corn paste and black sesame paste) have defects such as uneven echoes, poor suspension stability, and poor sound transmission. They tend to settle and separate after standing, resulting in significant posterior sound attenuation and failing to clearly display the posterior wall structure of the gastrointestinal tract, thus affecting diagnostic accuracy.

[0003] Meanwhile, most existing contrast agents only have imaging function and no nutritional support function, making it difficult to meet the examination needs of malnourished or hospitalized patients who are not eating. In addition, some preparations are inconvenient to store and transport, and have high preparation costs.

[0004] Therefore, developing a gastrointestinal ultrasound contrast agent that is highly biocompatible, has excellent acoustic properties, is well-tolerated by patients, and is both convenient and functional has become an urgent problem to be solved. Summary of the Invention

[0005] To address the shortcomings of existing gastrointestinal ultrasound contrast agents, the present invention aims to provide a tsampa-based gastrointestinal ultrasound contrast agent. This contrast agent uses pure natural tsampa powder from the Qinghai-Tibet Plateau as its core matrix. After ultra-fine grinding and sterilization, it is combined with natural suspending stabilizers, food-grade defoamers, and flavoring agents, and mixed with warm water in a specific ratio to form a suspension. Its preparation process includes three steps: raw material pretreatment, dry mixing, and suspension preparation, and is simple to operate. This invention achieves adjustable acoustic characteristics by controlling parameters such as the particle size (over 90% of particles are 10-50 μm) and concentration of the tsampa powder. In vitro testing shows that this contrast agent has a moderately fine echo, is stable in suspension for 30 minutes, and exhibits no acoustic attenuation.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: The application of tsampa in the preparation of a gastrointestinal ultrasound contrast agent, wherein the contrast agent is prepared by mixing pure tsampa powder that has been ultra-finely pulverized with warm water; The pure tsampa powder that has been ultra-finely pulverized has a particle size of over 90% of its particles in the range of 10 to 50 μm. The mass ratio of pure tsampa powder to warm water is (8~12g):100mL; The temperature of the warm water is 35~45℃; The contrast agent exhibits moderately dense and uniform echoes in non-therapeutic ultrasound imaging, shows no sedimentation or precipitation after standing for 25-30 minutes, and shows no acoustic attenuation in the background.

[0007] Preferably, more than 90% of the tsampa powder particles have a particle size of 50 μm; The mass ratio of the pure tsampa powder to warm water is 10g:100mL; The temperature of the warm water is 40℃.

[0008] Preferably, the contrast agent also includes excipients that do not affect acoustic performance; The excipients include suspension stabilizers, food-grade defoamers, and flavoring agents; The suspension stabilizer accounts for 0.1% to 0.5% of the total mass of the contrast agent; The edible defoamer accounts for 0.01~0.05% of the total mass of the contrast agent; The flavoring agent accounts for 0.5-2% of the total mass of the contrast agent.

[0009] Preferably, the suspension stabilizer accounts for 0.3% of the total mass of the contrast agent; The edible defoamer accounts for 0.03% of the total mass of the contrast agent; The flavoring agent accounts for 1% of the total mass of the contrast agent.

[0010] Preferably, the suspension stabilizer includes natural edible gum suspension stabilizers; The natural edible gum suspension stabilizers include guar gum and / or xanthan gum.

[0011] Preferably, the edible defoamer is food-grade polydimethylsiloxane.

[0012] Preferably, the flavoring agent is food-grade xylitol.

[0013] A tsampa gastrointestinal ultrasound contrast agent, wherein the contrast agent is a viscous suspension prepared by mixing ultra-finely pulverized pure tsampa powder as the core matrix with warm water at 35~45℃. The pure tsampa flour is roasted barley flour, with over 90% of the particles having a diameter of 10~50μm.

[0014] A method for preparing a tsampa-based gastrointestinal ultrasound contrast agent includes the following steps: S1. Raw material pretreatment: Select pure tsampa powder without additives, ultrafine grind it to a particle size of 10~50μm for more than 90% of the particles, and then sterilize it with an irradiation dose of 5~15kGy. S2, Dry mixing + suspension preparation: After dry mixing the pretreated pure tsampa powder with the suspension stabilizer for 3-8 minutes until uniform, pour it into warm water and stir while adding for 2-6 minutes until a uniform, lump-free viscous suspension is formed.

[0015] Preferably, the stirring rate is 800~1500 r / min.

[0016] Compared with the prior art, the present invention has at least the following technical effects: This invention provides a tsampa gastrointestinal ultrasound contrast agent. The contrast agent uses pure natural tsampa powder from the Qinghai-Tibet Plateau as the core matrix. After being ultra-finely pulverized and sterilized, it is combined with natural suspension stabilizers, food-grade defoamers and flavoring agents, and mixed with warm water in a specific ratio to form a suspension.

[0017] The preparation process of this tsampa gastrointestinal ultrasound contrast agent includes three steps: raw material pretreatment, dry mixing, and suspension preparation, which is simple to operate.

[0018] This invention innovatively uses pure natural tsampa powder as the core matrix of the contrast agent. It contains no chemically synthesized components, pigments, or preservatives, exhibits extremely high biocompatibility, and has a very low risk of side effects. The dietary fiber in tsampa works synergistically with the starch. The dietary fiber forms a viscous colloid that stabilizes the suspension and prolongs the adhesion time to the gastrointestinal wall, while the gelatinized starch increases the viscosity of the liquid and provides a uniform acoustic interface. By adjusting parameters such as the particle size (over 90% of the particles are 10-50 μm) and concentration of the tsampa powder, the acoustic properties can be adjusted. In vitro testing shows that the contrast agent has a moderately fine echo, is stable in suspension within 30 minutes, and exhibits no acoustic attenuation. Combined with clinical use, it can clearly outline the structure of the gastrointestinal wall, and the imaging effect is better than existing contrast agents such as corn paste and black sesame paste; Tsampa is an edible staple food, has no odor, is less likely to cause abdominal distension, and is more easily accepted by patients, especially suitable for children, patients with sensitive constitutions, and patients who need repeated examinations, with good tolerance; The contrast agent is in solid powder form, which is easy to store and transport, can be prepared and used immediately, and has a simple preparation process, reducing the hospital's preparation cost.

[0019] Compared with existing contrast agents, the present invention has high biocompatibility, low side effects, good patient tolerance, and can also provide nutritional support. It is convenient to store and transport, has low preparation cost, and is suitable for gastrointestinal ultrasound examinations in various populations. Attached Figure Description

[0020] Figure 1 This is an ultrasound image of the gastric pouch model tested in Example 1; Figure 2 Ultrasound images of the gastric pouch model in Comparative Example 1; Figure 3 Ultrasound images of the gastric pouch model in Comparative Example 2; Figure 4 This is an ultrasound scan image obtained from a 3.5MHz convex array probe during a clinical trial of Example 1. Figure 5 This is an ultrasound scan image obtained from a 10MHz linear array probe during a clinical trial of Example 1. Figure 6 This is an ultrasound scan image obtained from a 3.5MHz convex array probe during a clinical trial of Example 1. Figure 7 This is an ultrasound scan image obtained from a 3.5MHz convex array probe during a clinical trial of Example 1. Detailed Implementation

[0021] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the present invention will be briefly introduced below in conjunction with the accompanying drawings and descriptions of the embodiments or the prior art. Obviously, the following description of the structure of the accompanying drawings is only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. It should be noted that the description of these embodiments is for the purpose of helping to understand the present invention, but does not constitute a limitation of the present invention.

[0022] Experimental detection methods: 1. In vitro acoustic testing methods Ultrasound diagnostic instruments were used for in vitro testing (in a gastric pouch model). The ultrasound probe frequency was 7-10MHz, and the dynamic range was 50-65%. The acoustic performance was tested at 0, 15, and 30 minutes after contrast agent modulation. Key test parameters included: echo intensity and uniformity (whether a uniform, moderate echo was formed (e.g., "cloudy" echo, and the echo should be moderately dense and consistent), suspension stability (no sedimentation within 30 minutes), sound transmission (no sound attenuation at the back, and clear visualization of the posterior wall), and viscosity (measured using a viscometer to suit the requirements of gastrointestinal flow and wall adhesion).

[0023] 2. Clinical usage methods Patients should fast for 6-12 hours (preferably 8 hours) before the examination. Adults should take 400-500 mL of contrast agent, while children under 18 years of age should take 5-10 mL / kg (preferably 8 mL / kg). The optimal time window for ultrasound scanning is 5-15 minutes after taking the contrast agent. Gastrointestinal scanning should be performed using conventional B-mode ultrasound or harmonic imaging mode with a probe frequency of 2.0-3.0 MHz.

[0024] Example 1: Preparation and Detection of Basic Tsampa Gastrointestinal Ultrasound Contrast Agent Raw material pretreatment: Select pure tsampa powder without additives, ultrafine grind it to more than 90% of the particles with a particle size of 50μm, and sterilize it by 10kGy irradiation; Preparation of suspension: Take 10g of sterilized tsampa powder, pour it into 100mL of 40℃ warm water, and stir at 1000r / min for 4min while adding the powder to form a viscous suspension without lumps.

[0025] like Figure 1 The image shown is an ultrasound image of the gastric pouch test. From top to bottom, it includes images after 1 minute of modulation; after 15 minutes of modulation; and after 30 minutes of modulation. Labeled parameters: TIS 0.0, MI 0.7, L12-5, 30Hz, dynamic range 62%; annotations include "medium, fine, and consistent echoes," "no subsidence, uniform echoes," and "no sedimentation, clear posterior wall visualization."

[0026] In vitro acoustic testing: An ultrasound diagnostic instrument with a probe frequency of 30Hz and a dynamic range of 62% was used for testing in a gastric pouch model. The results were combined with... Figure 1 Display: (1) Echo intensity and uniformity: The echo is moderate, dense and consistent. (2) Suspension stability: After standing (30 minutes), the stability is still good, there is no sinking phenomenon, and the echo is still uniform. (3) Sound transmission: There is no sound attenuation at the rear, and the "rear wall" is very clearly displayed.

[0027] Clinical testing trials: like Figure 4 The patient was given 500ml of tsampa contrast agent orally. A 3.5MHz convex array probe was used for ultrasound examination in the clinical trial; the dynamic range was 55°. Results showed that the stomach (lesser curvature, antrum, pylorus, etc.) and duodenal bulb structures were clearly visualized on ultrasound; image stability was maintained for over 30 minutes.

[0028] like Figure 5 The patient was given 500ml of tsampa contrast agent orally. An ultrasound scan was performed using a 10MHz linear array probe in the clinical trial; the dynamic range was 58°. Results showed that the gastric wall layer structure (mucosa, muscularis mucosae, submucosa, muscularis propria, and serosa) of the lesser curvature of the stomach was clearly displayed; image stability was over 30 minutes.

[0029] like Figure 6 The patient was given 500ml of tsampa contrast agent orally. Ultrasound scans were performed using a 3.5MHz convex array probe in the clinical trial; the dynamic range was 53°. Results showed that the sonographic image (longitudinal section) of the posterior wall of the duodenum was clearly displayed; image stability was over 30 minutes.

[0030] like Figure 7 The patient was given 500ml of tsampa contrast agent orally, and ultrasound images were scanned using a 3.5MHz convex array probe in a clinical trial. The dynamic range was 53°. Results showed that the sonographic image (transverse section) of the posterior wall of the duodenum was clearly displayed; image stability was over 30 minutes.

[0031] Comparative Example 1: A contrast agent prepared using plain, fragrant cornmeal paste. Results are as follows... Figure 2As shown, the left image is the detection image after 1 minute of modulation, and the right image is the detection image after 15 minutes of modulation. The parameters are labeled as follows: TIS 0.0, MI 0.7, L12-5, 30Hz, dynamic range 62%, and marked as "high and uneven echo, layering" and "coarse particle deposition at the bottom, sound attenuation at the rear".

[0032] The results are as follows Figure 2 The results show that: (1) Echo intensity and uniformity: The echo is high, uneven, and layered. (2) Suspension stability: After standing for 15 minutes, there are coarse particles at the bottom, and the echo intensity is uneven. (3) Sound transmission: There is sound attenuation at the back, and the "back wall" cannot be clearly displayed.

[0033] Comparative Example 2: A contrast agent prepared using southern black sesame paste. Results are as follows... Figure 3 As shown, the left image is the detection image after 1 minute of modulation, and the right image is the detection image after 15 minutes of modulation. The parameters are labeled as follows: TIS 0.0, MI 0.7, L12-5, 30Hz, dynamic range 62%; and are labeled as "high echo, uneven coarseness, initial stratification" and "sinking and precipitation, unclear back wall display".

[0034] The results are as follows Figure 3 The results show that: (1) Echo intensity and uniformity: The echo is too high and the texture is uneven, with layering visible even in the initial configuration. (2) Suspension stability: After standing for 15 minutes, it sinks and coarse particles settle at the bottom, with uneven echo intensity. (3) Sound transmission: There is no obvious sound attenuation at the rear, and the "rear wall" is not clearly visible.

[0035] Finally, it should be noted that the above description is merely a preferred embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. The application of tsampa in the preparation of a gastrointestinal ultrasound contrast agent, characterized in that, The contrast agent is prepared by mixing pure tsampa powder that has been ultra-finely pulverized with warm water; The pure tsampa powder that has been ultra-finely pulverized has a particle size of over 90% of its particles being between 10 and 50 μm. The mass ratio of pure tsampa powder to warm water is (8~12g):100mL; The temperature of the warm water is 35~45℃; The contrast agent exhibits moderately dense and uniform echoes in non-therapeutic ultrasound imaging, shows no sedimentation or precipitation after standing for 25-30 minutes, and shows no acoustic attenuation in the background.

2. The application of tsampa according to claim 1 in the preparation of a gastrointestinal ultrasound contrast agent, characterized in that, More than 90% of the tsampa powder particles have a diameter of 50μm; The mass ratio of the pure tsampa powder to warm water is 10g:100mL; The temperature of the warm water is 40℃.

3. The application of tsampa according to claim 1 or 2 in the preparation of a gastrointestinal ultrasound contrast agent, characterized in that, The contrast agent also includes excipients that do not affect acoustic performance; The excipients include suspension stabilizers, food-grade defoamers, and flavoring agents; The suspension stabilizer accounts for 0.1% to 0.5% of the total mass of the contrast agent; The edible defoamer accounts for 0.01~0.05% of the total mass of the contrast agent; The flavoring agent accounts for 0.5-2% of the total mass of the contrast agent.

4. The application of tsampa according to claim 3 in the preparation of a gastrointestinal ultrasound contrast agent, characterized in that, The suspension stabilizer accounts for 0.3% of the total mass of the contrast agent; The edible defoamer accounts for 0.03% of the total mass of the contrast agent; The flavoring agent accounts for 1% of the total mass of the contrast agent.

5. The application of tsampa according to claim 3 in the preparation of a gastrointestinal ultrasound contrast agent, characterized in that, The suspension stabilizer includes natural edible gum suspension stabilizers; The natural edible gum suspension stabilizers include guar gum and / or xanthan gum.

6. The application of tsampa according to claim 3 in the preparation of a gastrointestinal ultrasound contrast agent, characterized in that, The edible defoamer is food-grade polydimethylsiloxane.

7. The application of tsampa according to claim 3 in the preparation of a gastrointestinal ultrasound contrast agent, characterized in that, The flavoring agent is food-grade xylitol.

8. A tsampa-based gastrointestinal ultrasound contrast agent, characterized in that, The contrast agent is a viscous suspension prepared by mixing pure tsampa powder that has been ultra-finely pulverized as described in claim 1 with warm water at 35~45℃. The pure tsampa flour is roasted barley flour, with over 90% of the particles having a diameter of 10~50μm.

9. A method for preparing a tsampa gastrointestinal ultrasound contrast agent as described in claim 8, characterized in that, Includes the following steps: S1. Raw material pretreatment: Select pure tsampa powder without additives, ultrafine grind it to a particle size of 10~50μm for more than 90% of the particles, and then sterilize it with an irradiation dose of 5~15kGy. S2, Dry mixing + suspension preparation: After dry mixing the pretreated pure tsampa powder with the suspension stabilizer for 3-8 minutes until uniform, pour it into warm water and stir while adding for 2-6 minutes until a uniform, lump-free viscous suspension is formed.

10. A method for preparing a tsampa-based gastrointestinal ultrasound contrast agent according to claim 9, characterized in that, The stirring rate is 800~1500 r / min.

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