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A microbubble preparation for ultrasonic diagnosis and sonodynamic therapy and its preparation method

An ultrasonic diagnosis and microbubble technology, applied in the field of biomedical materials, can solve problems such as increasing the pain of patients, and achieve the effects of reducing drug intake, less drug leakage, and enhancing efficiency

Active Publication Date: 2020-02-18
PEKING UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Traditionally, diagnostic reagents and therapeutic reagents are independent of each other, and the two are administered successively, often more often, and increase the suffering of patients

Method used

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  • A microbubble preparation for ultrasonic diagnosis and sonodynamic therapy and its preparation method
  • A microbubble preparation for ultrasonic diagnosis and sonodynamic therapy and its preparation method
  • A microbubble preparation for ultrasonic diagnosis and sonodynamic therapy and its preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] A preparation method of the microbubble preparation is as follows figure 1 , As shown in 2, includes the following steps:

[0039] (1) Tiger Red Sodium Salt (0.5g, 4.92x 10 -4 mol), 8-bromooctanoic acid (0.33g, 1.48x 10 -3 mol) 5mL DMF was added and stirred at 80°C for 7 hours. After the DMF in the product was spin-dried under vacuum, 50mL of ether was added, stirred at room temperature 25°C for 18 hours, and filtered to obtain a red powder. Add 50mL of pure water to the red powder of the product, stir for 18 hours at room temperature 25 degrees Celsius, and filter to obtain product 1 0.44g, 3.95x10 -4 mol). Use mass spectrometry and nuclear magnetism to determine the relative molecular mass and structure of the product. 1 H NMR (500MHz, DMSO-d6): 0.80 (m, CH 2 ,2H),1.00(m,CH 2 ,2H),1.10(m,CH 2 ,4H),1.40(m,CH 2 ,2H),2.20(t,CH 2 COOH,2H),3.90(t,OCH 2 ,2H),7.50(s,ArH,2H),11.90(s,COOH,1H). Theoretical mass spectrum value: 1115.8, experimental value 1114.6. The reaction formul...

Embodiment 2

[0046] (1) Observe the microbubble preparations prepared in Example 1 under a fluorescence microscope to obtain imaging under white light and fluorescence images under 540nm green light excitation.

[0047] (2) Then take 1 mL of microbubbles for ultrasonic disintegration, perform dynamic light scattering and zeta potential evaluation, and then observe the nanoparticles under a transmission electron microscope to obtain image results.

[0048] The final result is image 3 As shown, the fluorescence image of the microbubble preparation illustrates the successful combination of rose bengal and the microbubbles, which are transformed into nanoparticles of appropriate size after ultrasonic disintegration.

Embodiment 3

[0050] The in vivo imaging effect evaluation of the microbubble preparation prepared in Example 1 mainly includes the following steps:

[0051] (1) Choose a 2-2.5kg female New Zealand white rabbit, and remove the abdominal hair. Urethane was injected via ear vein for anesthesia. The abdomen was coated with ultrasound coupling agent, and an ultrasound instrument was used for contrast-free renal radiography (frequency 3.5MHz, mechanical index 0.06 and 0.75). Save the image.

[0052] (2) Inject 1 mL of the microbubble preparation through the ear vein, and then inject 4 mL of normal saline to better enter the blood circulation. Then it was performed renal imaging (frequency of 5MHz, mechanical index of 0.06 and 0.75). Save the image.

[0053] The result is Figure 4 As shown, after the injection of rose bengal microbubbles, ultrasound contrast can be performed well under the condition of low mechanical index, which verifies its contrast function as microbubbles and proves that the pr...

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Abstract

The invention discloses a microbubble preparation for ultrasonic diagnosis and SDT (sonodynamic therapy) and a preparation method of the microbubble preparation. The microbubble preparation uses a rose-bengal long-chain compound and a surfactant as shell materials filled with gas, has the capabilities of ultrasonic imaging, ultrasonic located bursting and singlet oxygen production under ultrasonicstimulation, and can be used for tumor imaging and therapy. The drug loading capacity of microbubbles is improved effectively by drug synthesis and the microbubble preparation way, drug uptake of a tumor part is increased greatly by means of fixed-point bursting of the microbubbles by located ultrasound, and the tumor status is observed in real time through combination of ultrasonic imaging and therapy. The preparation can effectively increase diagnosis and treatment efficiency, is a high-efficiency novel drug loading system and has good clinical application prospects.

Description

Technical field [0001] The invention belongs to the field of biomedical materials, and specifically relates to an ultrasound contrast agent for ultrasound imaging diagnosis and sonodynamic therapy and a preparation method thereof. Background technique [0002] Cancer has always been a problem that plagues the world, and its increasing morbidity and mortality rates are a major challenge facing modern medicine. Chemotherapy is one of the important methods of cancer treatment, but after simple small molecule drugs enter the body, they will be rapidly metabolized by the liver and kidneys, resulting in shorter half-life and residence time in the body, and the distribution of some tumor drugs is not high, in order to achieve therapeutic effects , May cause the drug concentration in other organs to reach a level that is prone to toxicity. As an excellent drug delivery system, nanocarriers are gradually gaining attention. However, most nano-drug delivery systems utilize the EPR effect,...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/22A61K41/00A61K47/69A61P35/00
CPCA61K41/0033A61K47/6925A61K49/223A61P35/00
Inventor 王凡梁晓龙侯睿李小达史继云马晓途张旭
Owner PEKING UNIV