A kind of urokinase preparation based on polymer carrier and its preparation method

A polymer carrier and urokinase technology, applied in the field of biomedicine, can solve the problems of low vascular recanalization rate and high bleeding complications, and achieve the effect of a safe and efficient method

Active Publication Date: 2020-05-08
PEKING UNIV FIRST HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, urokinase intravenous thrombolysis has two main problems: low recanalization rate and high bleeding complications. On the one hand, because the half-life is only 10-15 minutes, it can be used within a controllable dose for recanalization after proximal large vessel occlusion. The rate is only 10-20%. On the other hand, while urokinase activates the local plasminogen of the thrombus, it often acts on the thrombus and defective blood vessels in other parts of the body, causing bleeding complications. Once bleeding, the mortality rate is as high as 70%.

Method used

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  • A kind of urokinase preparation based on polymer carrier and its preparation method
  • A kind of urokinase preparation based on polymer carrier and its preparation method
  • A kind of urokinase preparation based on polymer carrier and its preparation method

Examples

Experimental program
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Effect test

Embodiment 1

[0046](1) Preparation of urokinase nanogel aqueous dispersion

[0047] Disperse the freeze-dried urokinase nanogel in 10mM phosphate buffer (pH 7.0-7.5) with a mass volume concentration of 10mg / mL, and disperse it in a water bath for 30min at 25°C to obtain a water-dispersed urokinase nanogel. liquid.

[0048] (2) Preparation of polyethylene glycol-polyethylene lactide solution

[0049] Polyethylene lactide-polyethylene glycol-polyethylene lactide triblock copolymer was synthesized according to literature method (Lee D.S., Shim M.S., Kim S.W., Lee H., Park I., Chang T.Novel thermoreversible gelation ofbiodegradable PLGA-block-PEO-block-PLGA triblock copolymers in aqueous solution.Macromol.Rapid Commun.2001,22,587-592), the average molecular weight is 7000Da, the molar ratio of polyester to polyethylene glycol is 2.9. At 40°C with a concentration of 10wt% Dissolve in dichloromethane to obtain polyethylene glycol-polyethylene lactide solution.

[0050] (3) Preparation of poly...

Embodiment 2

[0057] (1) Preparation of polyethylene glycol-polycaprolactone solution

[0058] Polyethylene glycol-polycaprolactone-polyethylene glycol triblock copolymers were synthesized according to literature method (Gong C., Shi S., Dong P., Kan B., Gou M., Wang X., Li X ., Luo F., Zhao X., Wei Y., Qian Z.Synthesis and characterization of PEG-PCL-PEG thermosensitivehydrogel.Int.J.Pharm.2009,365,89-99), average molecular weight 3000Da, polyester and poly The glycol ratio was 2.0. Dissolve it in dichloromethane at a concentration of 10 wt% at room temperature to obtain a polyethylene glycol-polycaprolactone solution.

[0059] (2) Preparation of polyethylene glycol-polycaprolactone aqueous dispersion

[0060] According to literature method (Yang S., Zhu F., Wang Q., Liang F., Qu X., Gan Z., Yang Z. Combinatorial targeting polymeric micelles for anti-tumor drug delivery. J. Mater. Chem. B, 2015, 3,4043-4051) to synthesize polyethylene glycol-polycaprolactone diblock copolymer with an av...

Embodiment 3

[0067] Embodiment 3, the in vitro release experiment of urokinase preparation

[0068] (1) Ultrasound responsiveness of urokinase preparation release

[0069] The urokinase preparation prepared in Example 1 was adjusted to 5 mg / mL with 10 nMPBS buffer at 37°C. The above dispersions were placed in six 5mL centrifuge tubes and incubated in a 37°C water bath at constant temperature. A group of three centrifuge tubes are continuously ultrasonicated with a transcranial Doppler ultrasonic device, and the ultrasonic frequency and power are 2MHz and 530mW / cm respectively 2 (experimental device such as figure 2 shown). Another set of three centrifuge tubes was not subjected to ultrasonic intervention. Draw a small amount of sample from the PBS solution containing drug-loaded nanogel at regular intervals with a 1mL syringe, filter it with a needle filter with a pore size of 200nm, and measure the content of urokinase in the filtrate with a BCA protein kit. The above experimental r...

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Abstract

The invention discloses a urokinase preparation based on polymer carriers and a preparing method of the urokinase preparation. The urokinase preparation comprises the carriers and content encapsulated in the carriers, wherein the carriers are polyethylene glycol-polyester block copolymer hollow gel particles; the content is polyethylene glycol crosslinked urokinase nano gel. The urokinase preparation has the advantages that ultrasonic-induced release is combined with environment pH response-induced release, the urokinase preparation is applicable to circulatory disturbance generated by feeding artery block, insufficient far-end tissue energy supply caused by the circulatory disturbance and microcirculation disturbance caused by secondary small embolism generated after great-vessel thrombolysis, partial and layered release of urokinase is promoted by external-field-effect active mediation and internal-environment passive targeting, urokinase action precision can be increased while the curative effect can be enhanced, and a safe and efficient method is provided for the treatment of acute cerebral ischemic stroke.

Description

technical field [0001] The invention relates to a polymer carrier-based urokinase preparation and a preparation method thereof, belonging to the field of biomedicine. Background technique [0002] With the acceleration of the aging trend of my country's population, the situation of prevention and treatment of cerebrovascular diseases will become more severe. Based on the theory of ischemic penumbra, the most effective treatment for acute ischemic stroke is still thrombolytic therapy and endovascular therapy, among which intravenous thrombolysis is still the most convenient, the most feasible and the most evidence-based medicine thrombolytic method. Urokinase is a thrombolytic drug widely used in China. Because of its cheap price and clear curative effect, it currently occupies a relatively wide market in the thrombolysis of cerebral infarction in my country. However, urokinase intravenous thrombolysis has two main problems: low recanalization rate and high bleeding complic...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/49A61K47/34A61P7/02
CPCA61K38/49A61K47/34C12Y304/21073
Inventor 金海强黄一宁刘冉孙伟平
Owner PEKING UNIV FIRST HOSPITAL
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