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RH (Rhein) liposome nanoparticles with kidney targeted distribution characteristics and application

A technology of distribution characteristics and lipid vesicles, which is applied to medical preparations with non-active ingredients, medical preparations containing active ingredients, organic active ingredients, etc., can solve the problems of not being able to effectively improve the efficacy of drugs, and achieve the improvement of multiple pathologies indicators, promote clinical transformation, and improve the effect of therapeutic effects

Active Publication Date: 2019-03-08
浙江省中医院、浙江中医药大学附属第一医院
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AI Technical Summary

Problems solved by technology

However, if the nanoparticles intercepted by the kidneys cannot be quickly absorbed and endocytized by the kidney cells, they will still be filtered and cleared by the kidneys, and the drug efficacy cannot be effectively improved.

Method used

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  • RH (Rhein) liposome nanoparticles with kidney targeted distribution characteristics and application
  • RH (Rhein) liposome nanoparticles with kidney targeted distribution characteristics and application
  • RH (Rhein) liposome nanoparticles with kidney targeted distribution characteristics and application

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Embodiment 1

[0030] 1 Materials and Instruments

[0031] Kidney Targeting Peptide KCSAVPLC (Kidney Targeting Peptide, KTP, entrusted to Shanghai Qiangyao Biotechnology Co., Ltd. to synthesize, purity ≥ 95%); RH API (Nanjing Zelang Pharmaceutical Technology Co., Ltd., purity ≥ 98%, batch number 201307); RH Reference substance (National Institute for Food and Drug Control, batch number 110757200206); Ethanolamine-polyethylene glycol 2000 (DSPE-PEG) (Shanghai Evert Pharmaceutical Technology Co., Ltd.); 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine-polyethylene glycol 2000-N- Hydroxysuccinimide (DSPE-PEG-NHS) (Nanosoft Polymers, USA); 2-methyl-2-oxazoline, methyl p-toluenesulfonate, 1-3′-dimethylaminopropyl-3 -Ethylcarbodiimide hydrochloride (EDC), N-hydroxysuccinimide (NHS) (Anaiji Chemical-Saen Chemical Technology Co., Ltd.); carboxyl-terminated polycaprolactone (PCL, molecular weight 3.7kD , Jinan Daigang Bioengineering Co., Ltd.); Thiazole blue (MTT) (Shanghai Aladdin Reagent Co., Ltd...

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Abstract

The invention relates to RH (rhein) liposome nanoparticles with kidney targeted distribution characteristics and an application of the RH liposome nanoparticles. The lipid capsule nanoparticles have the characteristics of higher encapsulation efficiency and drug loading capacity for RH, uniform particle size distribution, slow release with adoption of in-vitro release, rapid cell uptake, avoidanceof entering lysosome and good biological safety. In a streptozotocin-induced diabetic nephropathy mouse model, KLPPR (Kidney targeting peptide modified Liposomal PCL-PEI nanoparticle loading Rhein) has the good kidney targeted distribution characteristics, can significantly improve a plurality of pathological indexes of the diabetic nephropathy mouse and alleviate and reverse deterioration of thecourse of diabetic nephropathy, and effectively improves the therapeutic effect of RH on diabetic nephropathy. According to the nanoparticles, a brand-new strategy is provided for targeted treatmentof diabetic nephropathy, clinical transformation of RH drugs is further promoted, and an important reference is provided for research of novel nano-preparations of RH and similar drugs.

Description

(1) Technical field [0001] The invention relates to a rhein lipid vesicle nanoparticle with kidney-targeted distribution characteristics and an application thereof. (2) Background technology [0002] Rhein (RH) is an active ingredient isolated and extracted from traditional Chinese medicines such as Polygonaceae plants Rheum palmatum L., Tanguticum Maxim.ex Balf., and belongs to the monoanthracene nucleus1, 8-dihydroxyanthraquinone derivatives, pharmacological studies have confirmed that RH can significantly inhibit the proliferation, hypertrophy and extracellular matrix production of glomerular mesangial cells, and RH can inhibit TSP-1 and TGF-β1 of human renal tubular epithelial cells The mRNA transcription and protein expression of the protein protect the inherent function of the kidney, and play a multi-target and multi-level therapeutic role in the intervention of kidney diseases. However, RH has poor solubility, short half-life, low renal enrichment rate, low bioavail...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/34A61K47/42A61K31/192A61P13/12A61P3/10
CPCA61K9/5146A61K9/5169A61K31/192A61P3/10A61P13/12
Inventor 陈丹飞朱永琴罗静雯魏颖慧施晓伟盛丽先王国伟
Owner 浙江省中医院、浙江中医药大学附属第一医院
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