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Benzamide analog mediated brain-targeting delivery system

A technology of benzamide and drug delivery system, applied in the field of pharmaceutical preparations, to achieve the effect of simple preparation method, small molecular weight, avoiding risks and complicated drug delivery process

Active Publication Date: 2013-02-27
SHANGHAI WHITTLONG PHARMA INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are no reports on the construction of PEI brain-targeting vectors modified by benzamide analogs at home and abroad.

Method used

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  • Benzamide analog mediated brain-targeting delivery system
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  • Benzamide analog mediated brain-targeting delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Preparation of p-hydroxybenzoic acid-polyethyleneimine-IR820 (p-HA-PEI-IR820)

[0050] 1. Preparation of p-hydroxybenzoic acid-polyethyleneimine (p-HA-PEI)

[0051] Weigh 0.130g of PEI and dissolve in 3ml of DMF, dissolve 7.5mg of p-hydroxybenzoic acid and 9.5mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 1ml of DMF, and stir It was added dropwise into the DMF solution of PEI, and stirred overnight at room temperature to obtain a white suspension. Discard the precipitate after centrifugation, add 100ml of cold ether to the supernatant for precipitation treatment, discard the supernatant after centrifugation, and wash the precipitate with cold ether 3 times, 10ml each time. After vacuum drying for 24 hours, the product was dissolved in a small amount of double-distilled water (dH2O), eluted with dH2O on a G-25 gel column, and the corresponding components were collected and freeze-dried to obtain p-HA-PEI. The results of proton nuclear magnetic spe...

Embodiment 2

[0059] Animal Test of p-Hydroxybenzoic Acid-Polyethyleneimine-IR820 (p-HA-PEI-IR820) Intracerebral Drug Delivery System

[0060] 1. Distribution of p-hydroxybenzoic acid-polyethyleneimine-IR820 mouse living tissue

[0061] Weigh the appropriate amount of p-HA-PEI-IR820, PEI-IR820 and IR820 respectively, dissolve them with normal saline to prepare a 1 mg / ml solution, and inject 100 μl / mouse into the tail vein, respectively, at 0.5, 2, 4, The mice were anesthetized with 10% chloral hydrate at 12 and 24 hours, and the fluorescence distribution in the mice was observed in the live animal imaging system. It can be seen from the distribution diagram that p-HA-PEI-IR820 has obvious fluorescence distribution in the mouse brain, while IR820 and PEI-IR820 have no fluorescence distribution in the brain, suggesting that p-HA-PEI-IR820 can pass through p-hydroxybenzene Formic acid mediates penetration of the blood-brain barrier into the brain ( figure 1 ).

[0062] 2. Distribution of p-...

Embodiment 3

[0067] p-Hydroxybenzoic acid-polyethyleneimine 125 In vivo distribution test of marker I in mice

[0068] 1. p-hydroxybenzoic acid-polyethyleneimine 125 I mark ( 125 I-p-HA-PEI)

[0069] p-HA-PEI (65μg / μl) 50μl, add Na 125 I 0.702mCi, 40°C water bath reaction for 5 minutes, G-25 gel column purification, HPLC gradient elution, C-18 chromatographic column detection, labeling rate 100%, product activity 0.636mCi.

[0070] 2, 125 Distribution test of I-labeled p-hydroxybenzoic acid-polyethyleneimine in mice

[0071] mouse tail vein injection 125 I-p-HA-PEI solution 100 μl / only (0.199 μCi / μl, 1.0 μg / μL), anesthetized mice with 10% chloral hydrate at 0.5, 1, 2 and 4 hours after administration respectively, and cardiac perfusion normal saline 100ml / Only organs or tissues such as heart, lung, liver, spleen, kidney and brain were taken, weighed, radioactive counts were determined, and the percentage of tissue per unit weight in the total injected radioactive counts (ID% / g) was ...

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Abstract

The invention belongs to the field of medicinal preparations, and relates to a brain-targeting delivery system. The system comprises a mediating molecule, a vector and a medicament, wherein the mediating molecule is a benzamide analog, the vector is a polycation macromolecule, and the mediating molecule and the vector are combined by a covalence mode; and the medicament is carried through an entrapping or adsorption mode. In the system, in-vivo and in-vitro brain-targeting is characterized through a tracer technique to prompt that the delivery system can span a blood brain barrier, and a gene medicament and a diagnosis medicament are delivered into a brain, so the system can be used for brain disease diagnosis and treatment. The system can avoid potential risks of an enteroinvasive administration mode and a complicated administration process, and has the advantages of large administration quantity, simple administration mode and the like; and the brain-targeting mediated molecule has the advantages of small molecular weight, low price and availability and industrialization convenience.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a brain-targeted drug delivery system, in particular to a brain-targeted drug delivery system mediated by benzamide analogs. The drug delivery system can cross the blood-brain barrier, deliver gene drugs and diagnostic drugs to the brain, and can diagnose and treat brain diseases. Background technique [0002] There are a variety of receptors in the human brain, such as dopamine receptors, serotonin receptors, acetylcholine receptors, opioid receptors, etc. These receptors play an extremely important role in the physiological activities of the human body. Brain diseases such as brain tumors, central nervous system infections, chronic pain, drug-induced recessiveness, epilepsy, periodic migraine, neurodegenerative diseases, schizophrenia, etc. have a huge impact on human health. However, most active drugs cannot pass through the blood-brain barrier (BBB), which makes the ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/16A61K47/12A61K47/34A61K9/00A61K9/14A61K48/00A61K49/00A61K51/04A61P25/00A61P25/04A61P25/06A61P25/08A61P25/18A61K101/02A61K103/10A61K103/20A61K47/32
Inventor 陆伟跃孟庆刚李瑾顾炳余梅
Owner SHANGHAI WHITTLONG PHARMA INST
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