Preparation and application of novel antithrombotic polymer nano-drug

A nano-drug and anti-thrombotic technology, applied in nano-drug, nano-technology, nano-technology and other directions, can solve the problems of easily causing bleeding complications, interfering with the efficacy of warfarin, obvious side effects, etc., achieving easy operation, improving efficiency, Simple preparation process

Inactive Publication Date: 2017-05-31
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing antithrombotic drugs still have one or another problem in terms of safety, such as the side effects of the following four typical antithrombotic drugs: ① antiplatelet drug aspirin, adverse reactions mainly include bleeding, gastrointestinal irritation And diarrhea, rash, etc., especially when large doses are required, the side effects are more obvious and inevitable
②Urokinase and other traditional thrombolytic drugs are more likely to cause bleeding complications and cause adverse reactions in the skin, spirit, blood, cardiovascular, urinary and other systems
Especially anticoagulant antithrombotic drugs, bleeding side effects are more prominent, ③ warfarin, the most important oral anticoagulant drug, but its ad

Method used

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  • Preparation and application of novel antithrombotic polymer nano-drug
  • Preparation and application of novel antithrombotic polymer nano-drug
  • Preparation and application of novel antithrombotic polymer nano-drug

Examples

Experimental program
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Effect test

Embodiment 1

[0053] Example 1: Synthesis of oleanolic acid-desulfated heparin polymer nanomedicine

[0054] Weigh an appropriate amount of oleanolic acid (OA) and place it in an eggplant-shaped bottle, add a mixture of tetrahydrofuran and N,N-dimethylformamide to dissolve completely, the molar concentration of OA is 0.1mmol / mL, ice bath, in an inert gas Under protected conditions, add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) and 1-hydroxybenzotriazole (HOBT) sequentially, OA, EDCI, HOBT The molar ratios are 1:1.4:1.4 in turn. React in an ice bath for 60 minutes, then slowly add it dropwise to p-phenylenediamine, the molar ratio of OA to p-phenylenediamine is 1:2, control the drop rate at an interval of 10 seconds between each drop, and react at a reaction temperature of 36°C for another 12 hours to saturate Precipitate with salt water, filter, pickle in turn, wash with water, and dry in vacuum to obtain powder OA-NH 2 . Weigh an appropriate amount of desulfated...

Embodiment 2

[0055] Embodiment 2: the synthesis of curcumin-low molecular weight heparin polymer nano drug

[0056] Weigh an appropriate amount of curcumin and low-molecular-weight heparin (the molar ratio of curcumin and low-molecular-weight heparin is 2:1), dissolve them completely with formamide respectively, and add DMAP, EDC and NHS (LMWH, DMAP, EDC, the molar ratio of NHS is 1: 0.2: 3: 3), ice-bath reaction 30min, under the dark condition, slowly add curcumin solution in the LMWH reaction solution again, control dripping speed be every drop interval 5 seconds, Reaction at room temperature for 24h. Add an excess volume of ice acetone to precipitate the product, and filter with suction to obtain the product. The product was reconstituted with ultrapure water, sonicated by the probe for 40 minutes, dialyzed in distilled water for 2 days (MWCO=3500), passed through a 0.8 μm microporous membrane, and freeze-dried to obtain curcumin-low molecular weight heparin polymer nanomedicine.

Embodiment 3

[0057] Embodiment 3: the synthesis of ursolic acid-low molecular weight heparin polymer nano-medicine

[0058] Weigh an appropriate amount of ursolic acid (UA) and place it in an eggplant-shaped bottle, add tetrahydrofuran to dissolve it completely, the molar concentration of UA is 0.05mmol / mL, put it in an ice bath, and under the protection of an inert gas, add dicyclohexylcarbodia Amine (DCC) and hydroxysuccinimide (NHS), the molar ratio of UA, DCC, and NHS is 1:1.2:1.2 in sequence. React in ice bath for 30min, move to room temperature for 24h. The precipitate dicyclohexyl urea (DCU) was removed by vacuum filtration to obtain a filtrate. The filtrate was precipitated with 3 times the amount of n-hexane for 12 h, filtered, and dried in vacuo to obtain succinimide-based UA. Weigh an appropriate amount of succinimide-based UA and dissolve it with N,N-dimethylformamide (DMF), slowly add it dropwise to o-phenylenediamine, the molar ratio of UA to o-phenylenediamine is 1:1, and ...

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Abstract

The invention relates to a novel antithrombotic polymer nano-drug. The novel antithrombotic polymer nano-drug is prepared by connecting a hydrophobic antithrombotic substance with a hydrophilic antithrombotic substance by means of a simple chemical reaction; the novel antithrombotic polymer nano-drug can be separately used as a polymer nano-drug, and can be also prepared into a polymer nano-drug composition by being physically coated with other pharmaceutically active or pharmacologically active molecules so as to improve the antithrombotic activity of the pharmaceutically active or pharmacologically active molecules. The antithrombotic polymer nano-drug not only improves the water solubility and stability of the hydrophobic antithrombotic substance, prolongs the action time of the hydrophobic antithrombotic substance and increases the concentration of the drug reaching the part with thrombus, but also reduces the bleeding risk of heparin of the hydrophilic antithrombotic substance and derivatives thereof and realizes the cooperative utilization of two different action mechanisms, thus giving play to higher antithrombotic activity. By adding corresponding medical auxiliary materials, the antithrombotic polymer nano-drug and a composition thereof can be prepared into corresponding preparations used for injection, oral administration or ophthalmic drug delivery. The preparation method of the novel antithrombotic polymer nano-drug is simple and lower in cost, thus being suitable for large-scale continuous production.

Description

technical field [0001] The invention relates to the preparation and application of a novel antithrombotic polymer nano drug. Background technique [0002] Diseases that seriously endanger human health, especially the eyes, heart and brain, and blood vessels of the elderly, are closely related to thrombosis. After entering the 21st century, thrombosis has become the world's largest cause of death, and thrombosis is a group A multifactorial change process in which genetic and environmental factors interact and influence each other. The main characteristics of common clinical thrombosis patients are familial heredity, recurrence, severity of symptoms, abnormal thrombosis site, and younger onset time. [0003] The formation of thrombus is generally the cause or complication of various diseases, such as blindness, pulmonary thromboembolism, atherosclerosis, coronary heart disease, cerebrovascular disease, deep vein embolism after surgery or trauma, etc. Among them, fundus venou...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/61A61K45/06A61P35/00C08B37/10B82Y5/00A61K31/704A61K31/56A61K31/12
CPCA61K45/06A61K31/12A61K31/56A61K31/704B82Y5/00C08B37/0075
Inventor 姚静吴园园
Owner CHINA PHARM UNIV
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