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Urokinase-loaded microbubbles targeting d-dimer monoclonal antibody for the treatment of pulmonary thromboembolism

A monoclonal antibody, dimer technology, applied in the field of medicine, can solve the problems of high mortality, high risk, active bleeding or bleeding, etc., and achieve the effect of low bleeding risk, good thrombolytic effect and small drug dose

Inactive Publication Date: 2020-12-15
THE AFFILIATED SIR RUN RUN SHAW HOSPITAL OF SCHOOL OF MEDICINE ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Anticoagulant and thrombolytic drugs can dissolve thrombus, but at the same time, there is a risk of aggravating bleeding. At present, many patients diagnosed with PTE have active bleeding or high risk of bleeding (surgical site bleeding, cerebral hemorrhage, coagulation dysfunction, etc.), This limits the use of these drugs
In cases where anticoagulant drugs and thrombolytic drugs are contraindicated, catheter-intervened descending pulmonary artery thrombectomy and thrombolysis can be considered, but this method is invasive and risky, and may cause cardiac arrest, bleeding or even death. Many units Difficult to carry out
As for surgical thrombectomy, it is a type of high-risk operation that must be performed under extracorporeal circulation. The risk is greater and the mortality rate is higher. It is difficult for ordinary hospitals to perform it.
The inferior vena cava filter can only be used to prevent pulmonary embolism, but cannot treat pulmonary embolism

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] A urokinase-loaded microbubble for the treatment of pulmonary thromboembolism using D-dimer monoclonal antibody as a targeting device. Biotinylated D-dimer monoclonal antibody. The particle size of the microbubbles is 1.2-2.2 microns.

[0033] The preparation method of the microbubbles loaded with urokinase is as follows:

[0034]1) Preparation of ultrasonic microbubbles: Dissolve distearoylphosphatidylcholine, 1,2-palmitoylphosphatidylglycerol, distearoylphosphatidylethanolamine-PEG2000 at a molar ratio of 85:10:5 in three Chloromethane and mixed on a vortex mixer; remove chloroform with dry nitrogen, dry in a vacuum oven for more than 2 h; add degassed Tris buffer solution (containing 10% glycerol and volume fraction 10% propylene glycol) to obtain a 3mg / mL phospholipid solution; heat the phospholipid solution to a phase transition temperature of 58°C, disperse the solution until transparent with a water-bath ultrasonic oscillator, and put it into a vial; replace th...

Embodiment 2

[0039] A urokinase-loaded microbubble for the treatment of pulmonary thromboembolism using D-dimer monoclonal antibody as a targeting device. Biotinylated D-dimer monoclonal antibody. The particle size of the microbubbles is 1.2-2.2 microns.

[0040] The preparation method of the microbubbles loaded with urokinase is as follows:

[0041] 1) Preparation of ultrasonic microbubbles: Dissolve distearoylphosphatidylcholine, 1,2-palmitoylphosphatidylglycerol, distearoylphosphatidylethanolamine-PEG2000 in a molar ratio of 88:9:3 in three Chloromethane and mixed on a vortex mixer; remove chloroform with dry nitrogen, and dry in a vacuum oven for more than 2 h; add degassed Tris buffer solution (containing 8% glycerol and volume fraction 12% propylene glycol) to obtain a 2.5mg / mL phospholipid solution; heat the phospholipid solution to a phase transition temperature of 55°C, disperse the solution until transparent with a water-bath ultrasonic oscillator, and divide it into a vial; pu...

Embodiment 3

[0046] A urokinase-loaded microbubble for the treatment of pulmonary thromboembolism using D-dimer monoclonal antibody as a targeting device. Biotinylated D-dimer monoclonal antibody. The particle size of the microbubbles is 1.2-2.2 microns.

[0047] The preparation method of the microbubbles loaded with urokinase is as follows:

[0048] 1) Preparation of ultrasonic microbubbles: Dissolve distearoylphosphatidylcholine, 1,2-palmitoylphosphatidylglycerol, distearoylphosphatidylethanolamine-PEG2000 at a molar ratio of 83:12:5 in three Chloromethane and mixed on a vortex mixer; remove chloroform with dry nitrogen, and dry in a vacuum oven for more than 2 h; add degassed Tris buffer solution (containing 12% glycerol and volume fraction 8% propylene glycol) to obtain a 3.5 mg / mL phospholipid solution; heat the phospholipid solution to a phase transition temperature of 60°C, disperse the solution until transparent with a water-bath ultrasonic oscillator, and put it into a vial; put...

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Abstract

The invention relates to the field of medicine and discloses a urokinase supported microbubble used for treating PTE (pulmonary thromboembolism) and adopting a D-dimer monoclonal antibody as a targetdevice. The microbubble is of phospholipid texture, a thrombolytic drug is supported on the microbubble, and the D-dimer monoclonal antibody is attached to the surface of the microbubble. The drug supported microbubble can be specifically bonded with a D-dimer on a thrombus through the D-dimer monoclonal antibody, so that the drug supported microbubble is bonded with the thrombus, then the in-vivodrug supported microbubble breaks under the action of inertial cavitation produced by in-vitro ultrasonic irradiation, and fixed-point release of the thrombolytic drug is realized. The drug is limited at the thrombus part, wounds are avoided, the bleeding risk is low, the microbubble is small in drug dose and good in thrombolytic effect, and the operation is controllable.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a urokinase-loaded microvesicle which uses D-dimer monoclonal antibody as a targeting device for treating pulmonary thromboembolism. Background technique [0002] Pulmonary thromboembolism (PTE) is a disease with pulmonary circulation and respiratory dysfunction as the main clinical manifestations and pathophysiological features caused by thrombus from the venous system or right heart blocking the pulmonary artery and its branches. PTE was considered a rare disease in the past, but in recent years, due to the improvement of people's awareness and level of diagnosis of PTE, the diagnosis rate of PTE has increased significantly. It is currently believed that its incidence rate is second only to hypertension and coronary heart disease in cardiovascular diseases. In China , The incidence of PTE in autopsy is 3%-11%, which is a common disease. And the disease has a high mortality rate. In th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/22A61K41/00A61K9/127A61K38/49A61K47/24A61K47/42A61P7/02A61P11/00
CPCA61K9/1271A61K38/49A61K41/0028A61K47/24A61K47/42C12Y304/21073
Inventor 章锐锋梁黎马国锋许晓玲
Owner THE AFFILIATED SIR RUN RUN SHAW HOSPITAL OF SCHOOL OF MEDICINE ZHEJIANG UNIV
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