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Urease-driven neutrophil drug delivery system and synthesis method thereof

A neutrophil and drug delivery system technology, applied in the field of urease-driven neutrophil drug delivery system and its synthesis, can solve problems such as poor thrombus targeting, and achieve the effect of accelerating the targeting rate

Pending Publication Date: 2022-05-31
厦门大学附属心血管病医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In order to solve the problem of poor thrombus targeting of the thrombolytic drug urokinase, the present invention intends to construct a urease-driven neutrophil drug delivery system to accurately target the thrombolytic drug urokinase to the thrombus formation site, and carry out safe and efficient Thrombolysis

Method used

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  • Urease-driven neutrophil drug delivery system and synthesis method thereof
  • Urease-driven neutrophil drug delivery system and synthesis method thereof
  • Urease-driven neutrophil drug delivery system and synthesis method thereof

Examples

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preparation example Construction

[0037] see figure 1 , a synthetic method of a urease-driven neutrophil drug delivery system proposed by the present invention, comprising the following steps:

[0038] S1, mixing a urease solution and a sulfo-NHS-Biotin solution, stirring and reacting at 0-10°C for 10-60 minutes, and dialyzing the reacted liquid to obtain the urease- Biotin (Urease-Biotin). Optionally, the volume of the urease solution is 1 mL and the concentration is 1 mg / mL, and the volume of the sulfo-NHS biotin solution is 1 mL and the concentration is 166 μM. The dialysis process may be as follows: a 1 kDa dialysis bag is used to load the reacted liquid and immersed in phosphate buffered saline solution for 8-16 hours. After dialysis, the obtained urease-biotin can also be dispersed in a phosphate buffered saline solution and stored at 4°C.

[0039]S2, use L-polylysine (PLL) solution to coat the culture vessel (such as a 12-well plate), add the neutrophils (neutrophils) solution to the culture vessel, ...

Embodiment 1

[0045] In this example, a urease-driven neutrophil drug delivery system is synthesized. For the overall synthesis steps, please refer to figure 1 .

[0046] First, if figure 2 As indicated, react urease (Urease) with sulfo-NHS-Biotin (sulfo-NHS-Biotin) to synthesize Urease-Biotin (urease-biotin), specifically: sulfo-NHS-biotin (1 mL; PBS, 166 μM ;) mixed with urease Urease solution (1 mL, 1 mg / mL), and stirred at low temperature for 30 min. After the reaction, the cells were dialyzed in PBS for 12 h with a 1 kDa dialysis bag. The obtained urease-biotin (Urease-Biotin) was dispersed in 2 mL of PBS (phosphate-buffered saline), and stored at a low temperature of 4°C. Wherein, the complete structural formula of sulfo-NHS-Biotin (sulfo-NHS-Biotin) is as follows image 3 shown.

[0047] Then, urease-biotin Urease-Biotin was used to modify neutrophils (Neutrophils), specifically: firstly, L-poly-lysine (PLL, 100ug / mL) was coated on a 12-well plate and left overnight for use. T...

Embodiment 2

[0049] In this example, a urease-driven neutrophil drug delivery system UBSB-NEs (Ag-UK) and / or Urease-NEs (Ag-UK) was synthesized by the following method.

[0050] The urine sensitization is loaded on the surface of nano silver to obtain "nano thrombolytic enzyme (Ag-UK)", and then the Ag-UK is injected into the UBSB-NEs and Urease-NEs synthesized in Example 1 to obtain a urea Enzyme-driven neutrophil drug delivery system UBSB-NEs(Ag-UK) and / or Urease-NEs(Ag-UK).

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Abstract

The invention discloses a urease-driven neutrophil drug delivery system and a synthesis method thereof. The preparation method comprises the following steps: firstly, reacting a urease solution with a sulfo-NHS biotin solution to obtain urease-biotin; the preparation method comprises the following steps: preparing L-polylysine, coating a culture vessel with an L-polylysine solution, adding a neutrophil solution, centrifuging to rotate neutrophil to the surface of the L-polylysine, removing supernate, sequentially adding a sulfo-NHS biotin solution, a streptavidin solution and urease-biotin for cell incubation to obtain urease modified neutrophil, and carrying out freeze-drying to obtain the neutrophil. And separating the levorotatory polylysine from the surface of the levorotatory polylysine to obtain the drug delivery system. The urease is fixed on one side of the neutrophil by utilizing the principle of specific binding of biotin / streptavidin, and the urease can quickly catalyze and decompose a large amount of urea in blood to generate carbon dioxide and ammonia gas, so that the movement of the neutrophil is promoted, the thrombus targeting of the neutrophil is combined, and the thrombus targeting effect of the neutrophil is improved. The action efficiency of thrombolytic drug urokinase can be improved.

Description

technical field [0001] The invention relates to the field of systems for thrombus treatment, and in particular to a urease-driven neutrophil drug delivery system and a synthesis method thereof. Background technique [0002] A thrombus is a small piece of blood that forms on the surface of a vessel in the cardiovascular system where the lining has been peeled off or repaired. In variable flow dependent patterns, thrombi consist of insoluble fibrin, deposited platelets, accumulated leukocytes, and trapped erythrocytes. [0003] As a thrombolytic drug, urosensitivity can directly act on the endogenous fibrinolytic system after intravenous infusion to catalyze the cleavage of plasminogen into plasmin, which can not only degrade fibrin clots, but also Degrade fibrinogen, coagulation factor V and coagulation factor VIII in the blood circulation, thereby exerting thrombolytic effect. However, simple urinary irritation has the disadvantage of poor thrombus targeting. [0004] Neu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/49A61K47/46A61K47/42A61K33/38A61P7/02C12N11/16C12N9/80
CPCA61K38/49A61K47/46A61K47/42A61K33/38A61P7/02C12N11/16C12N9/80C12Y305/01005A61K2300/00Y02A50/30
Inventor 桑芒芒郑锦荣王焱
Owner 厦门大学附属心血管病医院