Amphotericin B polypeptide hydrogel drug carrier system for treatment of fungal infection

A technology for amphotericin and fungal infection, applied in antifungal agents, dipeptide components, pharmaceutical formulations, etc., can solve the problems of low biocompatibility, bioavailability, clinical toxic and side effects, etc., to improve the transfer efficiency in the body, reduce Clinical toxicity and side effects, and the effect of improving biocompatibility

Active Publication Date: 2017-11-24
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to provide three amphotericin B (abbreviated as AmB) polypeptide hydrogels for the treatment of fungal infections i

Method used

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  • Amphotericin B polypeptide hydrogel drug carrier system for treatment of fungal infection
  • Amphotericin B polypeptide hydrogel drug carrier system for treatment of fungal infection
  • Amphotericin B polypeptide hydrogel drug carrier system for treatment of fungal infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Weigh about 1.2g of 2-chlorotrityl chloride resin (1.0~1.2mmol / g) into the solid-phase synthesis tube, add 15mL of dichloromethane (DCM for short), swell for 20 minutes, filter, wash with DCM for 2min× 5 times. Add the first amino acid, 15mL DCM and N,N-diisopropylethylamine (DIPEA for short) to the above-mentioned solid-phase synthesis tube according to the dosage in Table 1, shake for 2 hours and drain, and wash with DCM for 2min×5 times. Add 10 mL of DCM / methanol / DIPEA (80:15:5) mixture to block the activated sites of the resin, shake for 15 min x 2 times, then drain, and wash with N,N-dimethylformamide (DMF) for 2 min x 5 times. Add 10 mL of 20% piperidine / DMF (V / V) solution and shake for 5 minutes to drain, add 10 mL of this solution and shake for 30 minutes, wash with DMF for 2 minutes x 5 times.

[0035] Add the second amino acid, 2-(7-azobenzotriazole)-tetramethyluronium hexafluorophosphate (referred to as HBTU) and 1-hydroxybenzotriazole (referred to as HOBT),...

Embodiment 2

[0040] According to the Nap-FFDKY compound prepared in Example 1, weigh 132.9 mg of the Nap-FFDKY compound and 92.41 mg of amphotericin B and dissolve them completely in 5 ml of DMF, add 41.25 μL of DIPEA, stir overnight in the dark, add glacial ether to disperse and extract, The solid was obtained by centrifugation, and was purified by HPLC after adding DMF to dissolve, and the purification conditions were as follows: the chromatographic column adopts Phenomenex Luna C 18 (50×300 mm, 10 μm), the mobile phase is methanol:water (55:45, V / V), the detection wavelength is 280 nm, and the flow rate is 15 ml / min. After preparation, the components were combined, concentrated by rotary evaporation, and freeze-dried to obtain the pure Nap-AmB product with a yield of about 69.1%.

Embodiment 3

[0042] According to the Npx-FFDKY compound prepared in Example 1, weigh 139.6 mg Npx-FFDKY and 92.41 mg amphotericin B and dissolve them completely in 5 ml DMF, add 41.25 μL DIPEA, stir overnight in the dark, add glacial ether to disperse and extract, and separate The obtained solid was purified by HPLC after adding DMF for dissolution, and the purification conditions were as follows: the chromatographic column adopts Phenomenex Luna C 18 (50×300 mm, 10 μm), the mobile phase is methanol:water (45:55, V / V), the detection wavelength is 280 nm, and the flow rate is 15 ml / min. After preparation, the components were combined, concentrated by rotary evaporation, and freeze-dried to obtain pure Npx-AmB with a yield of about 53.5%.

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Abstract

Belonging to the field of biotechnology, the invention in particular relates to an amphotericin B polypeptide hydrogel drug carrier system for treatment of fungal infection. According to the invention, polypeptide hydrogel with great clinical application potential is employed for covalent binding of small molecule hydrophobic antibacterial drug amphotericin B to form the amphotericin B polypeptide hydrogel nano-drug carrier system. The prepared nano-drug carrier system has the characteristics of high drug loading capacity, high biocompatibility and high stability, at the same time has the advantages of sustained or controlled release of drugs, easy degradation of polypeptide carrier, reduced clinical toxic and side effects and obvious antifungal effect. The amphotericin B polypeptide hydrogel nano-drug carrier system can be stored and used in the form of amphotericin B polypeptide hydrogel nano-drug carrier system, also can be diluted with water for injection so as to be suitable for intravenous injection, or can be incorporated with other auxiliary materials to be prepared into tablets, pills, granules or capsules. The amphotericin B polypeptide hydrogel nano-drug carrier system provided by the invention is suitable for the antifungal and fungal infection disease treatment field, and has good application prospect.

Description

technical field [0001] The invention belongs to the field of biotechnology, and relates to a novel amphotericin B polypeptide hydrogel nano drug loading system. In particular, it relates to three amphotericin B polypeptide hydrogel nano drug loading systems for treating fungal infections. Background technique [0002] Amphotericin B is a class of polyene macrolide antibiotics produced by Streptomyces nodosum, and it is mainly used clinically for deep fungal infections. Amphotericin B can specifically bind to ergosterol on the fungal cell membrane, and inhibit the growth of fungi by affecting the permeability of the cell membrane. It is clinically used to treat severe deep fungus-induced visceral or systemic infections. Although amphotericin B is effective and no obvious drug resistance has been found so far, it can cause strong nephrotoxicity, and long-term use will cause damage to the kidney and circulatory system. The clinical symptoms are proteinuria, low Potassium, ane...

Claims

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Application Information

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IPC IPC(8): A61K47/64A61K9/06A61K31/7048A61K38/05A61P31/10
CPCA61K9/06A61K31/7048A61K38/05A61K2300/00
Inventor 舒畅丁黎李腾飞
Owner CHINA PHARM UNIV
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