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Medicinal transferring system for intracephalic transference of medicine

A technology for delivery systems and drugs, which can be used in pharmaceutical formulations, medical preparations with non-active ingredients, and non-active ingredients in polymer compounds, etc. The effect of reducing the dosage, overcoming the instability of modification, and convenient preparation method

Inactive Publication Date: 2005-02-23
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In order to increase the drug-loading capacity of the system, it has been reported that linking cationized albumin to drug-loaded liposomes has been confirmed by in vitro experiments to increase the uptake of drugs by brain capillary endothelial cells, but liposomes are used as drug storage. The library still has problems such as low drug loading, unstable membrane and easy leakage of drugs
[0006] It was also reported that nanoparticles modified on the surface of Tween can increase the delivery of drugs in the brain, but since Tween is modified on the surface of nanoparticles by physical adsorption, after the nanoparticles enter the blood, the Tween on the surface is very easy. Dissociate and lose effect

Method used

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  • Medicinal transferring system for intracephalic transference of medicine
  • Medicinal transferring system for intracephalic transference of medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Preparation of a drug delivery system loaded with fluorescent dye 6-coumarin

[0032] 1) Slowly add 250ml of 0.9mol / L ethylenediamine to 4ml of 50% bovine serum albumin (BSA), stir while adding, adjust the pH to 4.75 with hydrochloric acid, add 360mg of EDAC, stir at room temperature for 2 hours, then add 1.3ml 4mol / L acetate buffer solution (pH 4.75), the solution was concentrated to 25ml, dialyzed for 72h, and freeze-dried to obtain CBSA. The molecular weight of the synthesized CBSA was identified by SDS-PAGE, and the isoelectric point was identified by isoelectric focusing electrophoresis (IEF). IEF results showed that the isoelectric point of CBSA was between 8-9, and SDS-PAGE showed that the molecular weight of CBSA was close to that of BSA, and the molecular weight was about 66000D.

[0033] Take 10 μl of 10 mg / ml S-acetyl-thioglycolic acid-N-succinimide (SATA) in dimethyl sulfoxide solution, add CBSA 1 mg (1 mg / ml) in HEPES solution (pH 7.4), stir for...

Embodiment 2

[0054] Example 2: Preparation of drug delivery system loaded with fluorescent dye 6-coumarin

[0055] 1) The method for preparing CBSA and mercaptolated CBSA is the same as in Example 1

[0056] Preparation of PEGylated nanoparticles loaded with 6-coumarin

[0057] Add 50 μl distilled water to 1 ml containing 24 mg monomethoxypolyethylene glycol 3000 - Polylactic acid 28600 (MPEG-PLA), 2.4mg maleimide-polyethylene glycol 3400 - Polylactic acid 23900 (maleimide-PEG-PLA) block copolymer and 15μg 6-coumarin in dichloromethane, 60W continuous ultrasonic 30s to prepare w / o type colostrum. Add colostrum into 2ml of 1% sodium cholate solution, and perform ultrasonication at 60W 30 times (1s / time) intermittently to obtain w / o / w type double emulsion. Add the double emulsion to 38ml of 0.5% sodium cholate solution, stir for 1min, remove methylene chloride by rotary evaporation at 40°C, centrifuge at 15000rpm at 4°C for 45min, remove the supernatant, and resuspend with 0.01mol / L pH7...

Embodiment 3

[0060] Example 3: Preparation of a drug delivery system loaded with the cerebral vasodilator nimodipine

[0061] 1) Slowly add 250ml of 0.9mol / L hexamethylenediamine to 4ml of 50% human serum albumin (HSA), stir while adding, adjust the pH to 4.75 with hydrochloric acid, and add 360mg of EDAC. After stirring at room temperature for 2 h, 1.3 ml of 4 mol / L acetate buffer (pH 4.75) was added. The solution was concentrated to 25ml, dialyzed for 72h, and freeze-dried to obtain CHSA. IEF showed that the isoelectric point of CHSA was between 8-9, and SDS-PAGE showed that the molecular weight of CHSA was close to that of HSA.

[0062] Take 150 μl of 1mg / ml Traut's reagent (2-iminothiolane) in borate buffer (pH 8.0), add CHSA 2mg (2mg / ml) in borate buffer (pH 8.0), stir for 60min, and pass through the reaction solution The buffer salt of Sephadex G-100 gel column was replaced with PBS at pH 7.4 to obtain thiolated CHSA. The degree of sulfhydrylation of CHSA determined by Ellman's re...

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Abstract

A medicine delivering system able to deliver medicine in brain for preventing, diagnosing and treating diseases is prepared from the nanoparticles as the medicine carrier and the cationized albumen which is co-valencely linked to the surface of said nanoparticle. It can carry the medicine through blood brain barrier into brain.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations and relates to a drug delivery system, in particular to a novel delivery system for delivering small molecule chemical drugs, diagnostic drugs, polypeptide protein drugs and gene drugs into the brain. Background technique [0002] The blood-brain barrier (BBB), composed of cerebrovascular endothelial cells, basement membrane and glial cells, limits the transport of substances into the brain. The vast majority of drugs do not or do not cross the BBB effectively. Therefore, in order to obtain the therapeutic concentration of the drug in the brain after the conventional route of administration, the dosage must be increased, which will cause a high concentration of the drug in the peripheral tissue and cause serious side effects on the body. [0003] The current techniques to overcome the BBB to increase drug delivery in the brain can be divided into two types: invasive and non-invasive. I...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K47/34A61K47/42
Inventor 陆伟蒋新国
Owner FUDAN UNIV
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