Cavitation microsphere for ultrasonic diagnosis of digestive tract
By designing cavitation microspheres for ultrasound diagnosis of digestive tract, the vibration of the microsphere core in the ultrasound field generates cavitation effect, and the targeting of lesion tissue is enhanced by targeting ligands, existing ultrasound imaging is solved The problem of poor agent stability and poor targeting has achieved efficient ultrasound imaging and accurate lesion diagnosis.
Patent Information
- Application Number
- CN202411648569.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-19
- Publication Date
- 2025-02-18
AI Technical Summary
Existing ultrasound contrast agents have poor stability and poor targeting in the diagnosis of digestive tract diseases, and it is difficult to effectively enhance the ultrasound imaging effect, especially in the diagnosis of early stages and minor lesions.
Using cavitated microspheres composed of microsphere cores, shells and targeting ligands, the targeting ligands are modified through the shell surface to enhance the targeting of lesion tissues, and the vibration and deformation of the microsphere cores in the ultrasonic field are used. A strong cavitation effect is generated and ultrasonic signal is enhanced.
The strong cavitation effect and good targeting of cavitation microspheres in the ultrasound field are achieved, the ultrasound imaging effect is enhanced, the visibility of the lesion tissue and the accuracy of diagnosis are improved, and the stability and Biocompatibility.
Smart Images
Figure CN119455024A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to a cavitation microsphere used for digestive tract ultrasonic diagnosis, belonging to the technical field of medical ultrasonic contrast agents. Background Art
[0002] With the continuous development of medical imaging technology, ultrasound imaging plays an increasingly important role in the diagnosis of gastrointestinal diseases. However, conventional ultrasound imaging has limited sensitivity and specificity in detecting gastrointestinal lesions, especially in the diagnosis of early lesions and small lesions.
[0003] At present, the ultrasound contrast agents on the market mainly include microbubble contrast agents and nanoparticle contrast agents. Microbubble contrast agents are usually composed of a gas core and a shell, which can produce strong echo signals in the ultrasound field and enhance the ultrasound imaging effect. However, microbubble contrast agents have poor stability, are easy to rupture, and have poor targeting to diseased tissues. Nanoparticle contrast agents have good stability and biocompatibility, but the echo signal in the ultrasound field is weak, and the contrast effect is not ideal. Summary of the invention
[0004] The purpose of the present invention is to provide a cavitation microsphere for digestive tract ultrasonic diagnosis, which has good targeting and stability.
[0005] The technical solution adopted by the present invention is:
[0006] A cavitation microsphere for digestive tract ultrasonic diagnosis consists of a microsphere core, an outer shell and a targeting ligand. The outer shell wraps the microsphere core, and the surface of the outer shell is modified with a targeting ligand.
[0007] Preferably, the material of the microsphere core is gas, liquid or solid.
[0008] Preferably, when the material of the microsphere core is gas, perfluorocarbon is used to prepare the microsphere core by emulsification or spray drying.
[0009] Preferably, when the material of the microsphere core is liquid, silicone oil or vegetable oil is used to prepare the microsphere core by solvent evaporation method or precipitation method.
[0010] Preferably, when the material of the microsphere core is solid, silica gel or calcium carbonate gel is used to prepare the microsphere core by a sol-gel method or a co-precipitation method.
[0011] Preferably, the material of the shell is polysaccharide, protein, polylactic acid, polycaprolactone or liposome.
[0012] Preferably, the thickness of the shell is in the range of 1% to 50% of the diameter of the microsphere, and the physical and chemical properties of the material are consistent with the raw material of the shell.
[0013] Preferably, the targeting ligand is selected from antibodies, polypeptides, and nucleic acid aptamers.
[0014] Preferably, the targeting ligand is modified onto the activated shell by chemical binding or physical adsorption.
[0015] The cavitation microspheres prepared by the present invention have the following performance characteristics:
[0016] ① Cavitation effect: The cavitation microspheres of the present invention can produce a strong cavitation effect in the ultrasonic field, thereby enhancing the ultrasonic signal. The cavitation effect is caused by the vibration and deformation of the microsphere core under the action of the ultrasonic field, which causes the pressure change of the surrounding liquid, and generates microbubbles and microjets. These microbubbles and microjets can scatter and reflect ultrasonic signals, thereby enhancing the ultrasonic imaging effect.
[0017] ② Targeting: Through surface modification of targeting ligands, the cavitation microspheres of the present invention can specifically bind to the diseased tissue and enhance the targeting to the diseased tissue. The targeting ligands can bind to specific receptors on the surface of the diseased tissue, thereby causing the microspheres to gather around the diseased tissue and improve the visibility of the diseased tissue.
[0018] ③ Stability: The cavitation microspheres of the present invention have good stability and can exist in the body for a long time without breaking or degrading. The material and structural design of the microsphere shell can effectively protect the microsphere core and prevent it from being affected by the external environment. At the same time, the connection method of the targeting ligand can also ensure its stability and biological activity in the body.
[0019] ④ Biocompatibility: The cavitation microspheres of the present invention have good biocompatibility and no toxic side effects on the human body. The materials of the microsphere shell and the selection of the targeting ligand have undergone strict biosafety assessments to ensure their safety and reliability in the body.
[0020] Beneficial effects:
[0021] (1) Enhanced ultrasound imaging effect: The cavitation microspheres of the present invention can produce a strong cavitation effect in the ultrasound field, enhance the ultrasound signal, and thus improve the visibility of the diseased tissue. Compared with traditional ultrasound contrast agents, the cavitation microspheres of the present invention can provide clearer and more accurate ultrasound images, which helps doctors to make early diagnosis and treatment of diseased tissues.
[0022] (2) Improve the targeting of diseased tissues: By modifying the surface with targeting ligands, the cavitation microspheres of the present invention can specifically bind to diseased tissues and enhance the targeting of diseased tissues. This helps to increase the concentration of ultrasound contrast agents in diseased tissues and improve the accuracy and specificity of diagnosis. At the same time, it can also reduce the side effects of ultrasound contrast agents on normal tissues and improve the safety and effectiveness of treatment.
[0023] (3) Good stability and biocompatibility: The cavitated microspheres of the present invention have good stability and biocompatibility and can exist in the body for a long time without breaking or degrading. This helps to improve the efficiency and safety of ultrasound contrast agents and reduce the pain and risks of patients. BRIEF DESCRIPTION OF THE DRAWINGS
[0024] Figure 1 The figure is a schematic diagram of the structure of the cavitation microspheres used for ultrasonic diagnosis of the digestive tract according to the present invention.
[0025] Figure 2 It is a schematic diagram of the use of the cavitation microspheres of the present invention. Specific implementation methods
[0027] The present invention is further described below in conjunction with embodiments, but the description of the embodiments does not impose any limitation on the protection scope of the present invention.
[0028] Unless otherwise defined, all technical terms and scientific terms used herein have the same meaning as those generally understood by those skilled in the art of the technical field of the present invention, and the terms used in the specification of the present invention herein are only for the purpose of describing specific embodiments, and are not intended to limit the present invention. In addition, although a demonstration of parameters containing specific values may be provided herein, it should be understood that the parameters do not need to be exactly equal to the corresponding values, but can be approximated to the corresponding values within an acceptable error tolerance or design constraint. The directional terms mentioned in the embodiments, such as "up", "down", "front", "back", "left", "right", etc., are only referenced to the directions of the accompanying drawings. Therefore, the directional terms used are used to illustrate rather than to limit the scope of protection of the present invention.
[0029] Unless otherwise specified, the materials and instruments used in the following examples can be obtained from conventional commercial channels. Example 1
[0030] 1. Materials and Equipment
[0031] (1) Materials: The core material of the microsphere is perfluorocarbon; the shell material is sodium alginate; the targeting ligand is mannose; the surfactant is polyvinyl alcohol.
[0032] (2) Equipment: agitator, ultrasonic device, heating device, centrifuge, drying oven, etc.
[0033] 2. Preparation Steps
[0034] (1) Preparation of microsphere core
[0035] Select the appropriate preparation method according to the material of the microsphere core. For example, for microspheres with a gasifiable core, an emulsification method can be used for preparation. The specific steps are as follows:
[0036] The perfluorocarbon core material of the microspheres is added to an aqueous solution containing 1 wt % of a surfactant (such as polyvinyl alcohol, Tween or poloxamer, etc.) at 4° C. to form an emulsion.
[0037] The perfluorocarbon is formed into a uniform emulsion, i.e. the core of the microsphere, by stirring and ultrasonication.
[0038] For liquid core microspheres, solvent evaporation method can be used to prepare them. The specific steps are as follows:
[0039] ① Dissolve the liquid core material (such as silicone oil, vegetable oil, etc.) in an organic solvent (such as ethanol, acetone, etc.) to form a solution.
[0040] ② Drop the solution into an aqueous solution containing 1 wt% of a surfactant (such as polyvinyl alcohol, Tween, poloxamer, etc.) to form an emulsion.
[0041] ③ The organic solvent in the emulsion is evaporated through stirring and ultrasound to form the microsphere core.
[0042] For microspheres with solid core, the sol-gel method can be used for preparation. The specific steps are as follows:
[0043] ① Dissolve the solid core material (such as silicon dioxide, calcium carbonate, etc.) in an organic solvent (such as dichloromethane, tetrahydrofuran, paraffin oil, etc.) to form a solution.
[0044] ② Drop the sol into an aqueous solution containing 1 wt% of a surfactant (such as polyvinyl alcohol, Tween, poloxamer, etc.) to form an emulsion.
[0045] ③ The sol in the emulsion is gelled through stirring and ultrasound to form the core of the microsphere.
[0046] (2) Shell coating
[0047] The prepared microsphere core is placed in a solution containing the shell material, and the shell material is uniformly coated on the surface of the microsphere core by stirring, ultrasound, etc. Then, the shell is cured by heating, cross-linking, etc. to form a stable microsphere structure. The specific steps are as follows:
[0048] ① Place the microsphere core at a ratio of 20% to 50% of the total weight into a solution containing 1 to 10 wt% of shell material (such as polysaccharide, protein, polylactic acid, polycaprolactone or liposome) and stir evenly.
[0049] ②Use ultrasonic instrument to treat the solution, the ultrasonic time is 0.5 to 10 minutes, and the power is 20 to 100W to make the shell material evenly coated on the surface of the microsphere core.
[0050] ③ Heat the solution to 60°C to solidify the shell material.
[0051] ④ Centrifuge the solution to remove uncoated shell materials and impurities.
[0052] ⑤ Clean the microspheres after centrifugation with a cleaning agent (such as ethanol, isopropanol, etc.), and then put them into a drying oven to dry, thereby obtaining microspheres coated with a shell.
[0053] (3) Targeting ligand attachment
[0054] The prepared microsphere shell is subjected to surface activation treatment, and then the targeting ligand is connected to the microsphere shell by chemical bonding, physical adsorption and other methods. Finally, the unbound targeting ligand is removed by washing, drying and other methods to obtain targeted cavitation microspheres. The specific steps are as follows:
[0055] ① Place the microspheres coated with the shell into a solution containing a surfactant (such as polyvinyl alcohol, Tween, poloxamer, etc.) for surface activation treatment.
[0056] ② Place the surface-activated microspheres into a solution containing targeting ligands (such as folic acid, mannitol, etc.), stir evenly, and attach the ligands to the surface of the microspheres through surface adsorption.
[0057] ③ The microspheres connected with the targeting ligands are cleaned with a cleaning agent, and then placed in a drying oven for drying to obtain targeted cavitation microspheres.
[0058] The structure of the prepared cavitation microspheres is as follows Figure 1 As shown, the size is usually 1 to 2000 μm, the innermost layer is the microsphere core 1, the microsphere core 1 is wrapped by the microsphere shell 2, and there is a layer of targeting ligand 3 on the shell.
[0059] The use of cavitation microspheres Figure 2 As shown, targeted cavitation microspheres are suspended in a buffer solution and injected into the digestive tract. The cavitation microspheres are adsorbed on the lesion site of the digestive tract, and the lesion site of the digestive tract can be located by ultrasonic scanning of the abdominal cavity.
[0060] The above embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with this technology to understand the contents of the present invention and implement them accordingly. They cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.
Claims
1. A cavitation microsphere for digestive tract ultrasonic diagnosis, characterized in that: The microsphere is composed of three parts: a microsphere core, a shell and a targeting ligand. The shell wraps the microsphere core, and the surface of the shell is modified with a targeting ligand.
2. The cavitation microsphere according to claim 1, characterized in that: The material of the microsphere core is gas, liquid or solid.
3. The cavitation microsphere according to claim 2, characterized in that: When the material of the microsphere core is gas, perfluorocarbon is used to prepare the microsphere core through an emulsification method or a spray drying method.
4. The cavitation microsphere according to claim 2, characterized in that: When the material of the microsphere core is liquid, silicone oil or vegetable oil is used to prepare the microsphere core through a solvent volatilization method or a precipitation method.
5. The cavitation microsphere according to claim 2, characterized in that: When the material of the microsphere core is solid, the microsphere core is prepared by using silica gel or calcium carbonate gel through a sol-gel method or a coprecipitation method.
6. The cavitation microsphere according to any one of claims 1 to 5, characterized in that: The material of the shell is polysaccharide, protein, polylactic acid, polycaprolactone or liposome.
7. The cavitation microsphere according to claim 6, characterized in that: The thickness of the shell is in the range of 1% to 50% of the diameter of the microsphere, and the physical and chemical properties of the material are consistent with the raw material of the shell.
8. The cavitation microsphere according to any one of claims 1 to 5, characterized in that: The targeting ligand is selected from antibodies, polypeptides, and nucleic acid aptamers.
9. The cavitation microsphere according to claim 8, characterized in that: The targeting ligand is modified onto the activated shell by chemical binding or physical adsorption.