Preparation and application of ultrasonically-controlled-release pluronic recombinant human tissue type plasiminogen activator

A technology of pluronic and plasminogen, applied in the field of medicine, can solve the problems of rebleeding, lack of treatment methods for hypertensive cerebral hemorrhage, short half-life, etc.

Inactive Publication Date: 2017-03-01
上海市浦东新区浦南医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Clinically, due to the rapid onset of rt-PA and its short half-life, the application of rt-PA may cause rebleeding during surgery, so rt-PA cannot be used during surgery.
[0005] In summary, there is curre

Method used

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  • Preparation and application of ultrasonically-controlled-release pluronic recombinant human tissue type plasiminogen activator
  • Preparation and application of ultrasonically-controlled-release pluronic recombinant human tissue type plasiminogen activator
  • Preparation and application of ultrasonically-controlled-release pluronic recombinant human tissue type plasiminogen activator

Examples

Experimental program
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Effect test

preparation example Construction

[0091] The present invention provides a kind of preparation method of described sustained-release pharmaceutical preparation, comprises the following steps:

[0092] (i) providing a raw material component comprising:

[0093] (a) recombinant tissue plasminogen activator rt-PA;

[0094] (b) Pluronic F127; and

[0095] (c) water;

[0096] (ii) Mix the raw material components to form a sol / gel mixture, which is the sustained-release pharmaceutical preparation described in the first aspect of the present invention.

[0097] Wherein, the mixing described in step (ii) includes: mixing rt-PA with water to prepare a first solution containing rt-PA, and then mixing the first solution with Pluronic F127 to form a first mixture.

[0098] In addition, the method may also include the steps of:

[0099] (iii) Put the sustained-release pharmaceutical preparation prepared in the previous step into a medical container.

[0100] Application method

[0101] The invention is used to prepar...

Embodiment 1

[0109] Example 1: Preparation of rt-PA-loaded nano-sustained-release pharmaceutical preparations and use of the preparations to complete in vitro hematoma dissolution

[0110] 1.1 Preparation of nano-sustained-release preparations loaded with rt-PA

[0111] At room temperature, commercially available rt-PA was dissolved with physiological saline to prepare a mixed solution with a concentration of 10 mg / ml. The Pluronic F-127 and the mixed solution are mixed according to the ratio of 190-290mg: 1ml (preferably, 230mg F-127 is mixed with 1ml of the mixed solution). Shake it on a vortex mixer for half an hour, and then place it in a refrigerator (5-15 degrees) for more than 8 hours to form a stable sol, store it in different containers according to the required dosage, and store it at room temperature or low temperature.

[0112] Experimental results: After Pluronic F127 is combined with rt-PA, the coating concentration ranges from 2-15mg / ml.

[0113] 1.2 Preparation of hematom...

Embodiment 2

[0126] Example 2. Sustained-release administration of Pluronic F-127 loaded with rt-PA, completing the in vivo animal experiment of ultrasound-induced controlled release

[0127] 2.1 Research objects: Recombinant human tissue-type plasminogen activator (Recombinant human tissue-type plasminogen, rt-PA); Pluronic F-127 and 50 male SD rats.

[0128] 2.2 Research grouping: N=50, 10 male SD rats in each group.

[0129] (1) Sham operation group: intracerebral puncture but no hematoma injection;

[0130] (2) Simple hematoma group: inject 50 μl of autologous arterial blood into intracerebral hematoma;

[0131] (3) Hematoma + rt-PA group: 50 μl of autologous arterial blood + rt-PA were injected into the intracerebral hematoma;

[0132] (4) Hematoma + non-ultrasound group with rt-PA Pluronic F-127 system: Inject 50 μl of autologous arterial blood into the intracerebral hematoma + rt-PA Pluronic F-127 system;

[0133] (5) Hematoma + rt-PA Pluronic F-127 system ultrasound group: 50 μl...

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Abstract

The invention discloses a preparation method for biodegradable recombinant human tissue type plasiminogen activator which realizes targeted release under ultrasonic control and application of the activator to promotion of lysis of hematoma, etc. Specifically, the invention relates to a slow-release medicinal preparation. The slow-release medicinal preparation comprises a human tissue type plasiminogen activator t-PV, pluronic F127 and water. The invention also discloses the function of a hydrogel and a micelle carrier in controlling drug release under ultrasonic action. The pluronic recombinant human tissue type plasiminogen activator is simple to prepare, suitable for large-scale production and especially applicable to removal of hematoma in the brain and preparation of antineoplastic drugs capable of realizing targetable drug delivery.

Description

technical field [0001] The invention belongs to the field of medicine, and specifically relates to a pharmaceutical preparation and its application of a pluronic copolymer and a recombinant tissue plasminogen activator as a drug-loading system. The hematoma dissolves. Background technique [0002] A pharmaceutical preparation is a collection of drugs and excipients, where the drug is the component that treats the symptoms in the drug preparation, and the excipients are used to stabilize, solubilize, aid in solubilization, relieve, control release, or facilitate the administration of the drug The general term for various ingredients other than drugs added for processing and processing. It is precisely because of the combination of drugs and excipients that pharmaceutical preparations can be applied and achieve certain curative effects. [0003] Hypertensive intracerebral hemorrhage (Hypertensive Intracerebral Hemorrhage, HICH) seriously endangers human health with its high ...

Claims

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Application Information

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IPC IPC(8): A61K38/49A61K47/10A61K41/00A61K9/06A61P9/12A61P29/00A61P7/04
Inventor 孙伟刘卫东
Owner 上海市浦东新区浦南医院
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