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Brain-targeted drug-delivery system, brain-targeted drug, and preparation methods of brain-targeted drug-delivery system and brain-targeted drug

A drug-carrying system and brain-targeting technology, which can be used in drug combinations, pharmaceutical formulations, neurological diseases, etc. Strong compatibility, excellent anti-epileptic effect, strong biocompatibility and safety effect

Inactive Publication Date: 2019-09-13
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most antiepileptic drugs are not brain-targeted, so the need for drugs will be greater, and drug resistance is prone to develop

Method used

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  • Brain-targeted drug-delivery system, brain-targeted drug, and preparation methods of brain-targeted drug-delivery system and brain-targeted drug
  • Brain-targeted drug-delivery system, brain-targeted drug, and preparation methods of brain-targeted drug-delivery system and brain-targeted drug
  • Brain-targeted drug-delivery system, brain-targeted drug, and preparation methods of brain-targeted drug-delivery system and brain-targeted drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] A preparation method of a brain-targeted drug.

[0040] 1. Preparation of drug-loaded system

[0041]Through genetic engineering technology, insert the modified peptide (sequence as shown in SEQ ID No.3) into the 78th to 81st amino acids of the core protein of hepatitis B virus to obtain a genetically modified expression plasmid, and transfect the modified plasmid into Escherichia coli Afterwards, streaking or flat laying in solid medium, after inverting overnight culture at 37°C, picking a single colony to expand culture in 2.5% LB medium until the OD600 reached 0.6-0.8, adding 0.1mM IPTG (volume ratio IPTG: LB medium = 1:10000) was induced and cultured at 18°C ​​for 20 h.

[0042] After the induction, the bacterial liquid was collected, centrifuged at 4000 rpm for 12 min at 4°C, the supernatant was discarded, and the precipitate was collected.

[0043] The precipitate was resuspended with Tris buffer (10 mM Tris-HCl, 0.5% (v / v) Triton-X-100), and the resuspended sol...

Embodiment 2

[0051] The targeting effect of the TGN-HBc VLPs provided in Example 1 was verified.

[0052] experimental method

[0053] The TGN-HBc VLPs provided in Example 1 were labeled with Cy5.5, and a set of comparisons was set as a control, using unmodified full-length HBc-183 VLPs.

[0054] 100 μL of TGN-HBc VLPs labeled with far-infrared dye Cy5.5 and unmodified full-length HBc-183 VLPs were injected intravenously into the tails of two groups of Balb / C nude mice, and the control dye concentration was 0.5 mg / mL.

[0055] After the mice were anesthetized with isoflurane, the fluorescence distribution in the whole body of the mice was detected by a small animal in vivo imager. After 2 hours and 8 hours, the mice were sacrificed by neck dislocation, and the brain tissue and other organs of the mice were collected to detect the fluorescence intensity. The fluorescence intensity data was processed with origin software and the distribution of fluorescence and its change over time were an...

Embodiment 3

[0060] The drug delivery effect of TGN-HBc / PHT VLPs provided in Example 1 was verified.

[0061] experimental method

[0062] The experimental mice were divided into five groups: normal saline group, TGN-HBc VLPs group, low-dose PHT group, high-dose PHT group, and low-dose TGN-HBc / PHT VLPs group.

[0063] Inject the drug to be tested, the total injection volume is 200 μL, and the drug concentration of the PBS group is 0 mg / kg, the drug concentration of the TGN-HBc VLPs group is 0 mg / kg, and the drug concentration of the PHT group is 0 mg / kg. The concentration of PHT in the PHT group was 20 mg / kg, and the concentration of PHT in the TGN-HBc / PHT VLPs group was 0.2 mg / kg. One hour after injection, N-bromomethylscopolamine was injected intraperitoneally at 1 mg / kg. Half an hour later, 300 mg / kg of pilocarpine was injected intraperitoneally. Seizures were monitored in real time for one hour.

[0064] Experimental results

[0065] EEG brain wave monitoring shows as attached Fi...

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Abstract

The invention discloses a brain-targeted drug-delivery system, a brain-targeted drug, and preparation methods of the brain-targeted drug-delivery system and the brain-targeted drug, and relates to thetechnical field of biological pharmacy. Specifically, the drug-delivery system comprises virus-like particles with a modification peptide modifying the surface, wherein the modification peptide comprises a trans-blood-brain barrier peptide and two connecting peptides for stabilizing the structure of the virus-like particles, the sequence of the connecting peptides is as shown in SEQ ID No.2, andthe connecting peptides are inserted into two ends of the trans-blood-brain barrier peptide. The drug-delivery system is used for loading therapeutic drugs, and can solve the technical problems of insufficient targeting property and overhigh drug dosage of the existing drugs for brain diseases. The drug-delivery system can realize the dual functions of blood-brain barrier crossing and targeting treatment of drugs.

Description

technical field [0001] The invention relates to the technical field of biopharmaceuticals, in particular to a brain-targeted drug-carrying system, a brain-targeted drug and a preparation method thereof. Background technique [0002] Epilepsy is a chronic disease in which the sudden abnormal discharge of brain neurons leads to transient brain dysfunction. According to the latest epidemiological data in China, the overall prevalence rate of epilepsy in China is 7.0‰, the annual incidence rate is 28.8 / 100,000, and the prevalence rate of active epilepsy with seizures within one year is 4.6‰. In China, epilepsy has become the second most common disease in neurology after headache. [0003] Antiepileptic drugs are of particular importance in the treatment of epileptic seizures. Antiepileptic drugs can eliminate or alleviate epileptic seizures in two ways. One is to affect the central neurons to prevent or reduce their pathological excessive discharge; the other is to increase th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/46A61K47/69A61K31/4166A61P25/28A61P25/08A61P25/00A61P35/00
CPCA61K9/5184A61K31/4166A61K47/6951A61P25/00A61P25/08A61P25/28A61P35/00
Inventor 任磊邵志成赵洁
Owner XIAMEN UNIV
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