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VCAM-1 monoclonal antibody tanshinone IIA nanostructure lipid carrier as well as preparation method and application thereof

A technology of VCAM-1 and nano-structured lipids, which is applied in the research field of new drug delivery systems, can solve the problems of increasing the incidence of adverse drug reactions, affecting the effective treatment of diseases, and low distribution, so as to improve the efficiency of drug treatment and relieve kidney pain. Inflammation level, effect of reducing distribution

Active Publication Date: 2021-01-15
TONGDE HOSPITAL OF ZHEJIANG PROVINCE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still many deficiencies in the use of this drug for DN: the drug has no specific selective effect on kidney tissue, resulting in a low distribution of the drug at the target site, which affects the effective treatment of the disease; the accumulation of the drug at the non-target site may increase the adverse reactions of the drug incidence rate

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  • VCAM-1 monoclonal antibody tanshinone IIA nanostructure lipid carrier as well as preparation method and application thereof
  • VCAM-1 monoclonal antibody tanshinone IIA nanostructure lipid carrier as well as preparation method and application thereof
  • VCAM-1 monoclonal antibody tanshinone IIA nanostructure lipid carrier as well as preparation method and application thereof

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preparation example Construction

[0031] On the other hand, the present invention provides a method for preparing VCAM-1 monoclonal antibody Tanshinone IIA lipid nanoparticles, the steps are as follows:

[0032] 1) Accurately weigh 10% Tanshinone IIA, 84%-89% glyceryl monostearate, 0%-5% polyethylene glycol monostearate (molecular weight: 2000) and 0.5% Monoamino-terminated polyethylene glycol stearate, a total of 99.5 mg of the above materials, mixed to obtain material A;

[0033] 2) Add 0.5mL of ethanol to material A, and heat it in a water bath at 60°C to completely dissolve it to obtain material B;

[0034] 3) Using deionized water as the dispersion medium, inject 0.5mL of material B into 9.5mL of deionized water heated in a 60°C water bath at a stirring speed of 400rpm, take it out after the injection is completed and stir for 30s, and naturally cool to room temperature to obtain tanshinone IIA lipid Bulk nano dispersion;

[0035] 4) Add N,N'-disuccinimidyl carbonate to the tanshinone IIA liposome nanop...

Embodiment 1

[0039] Example 1: Preparation of VCAM-1 monoclonal antibody Tanshinone IIA nanostructure lipid carrier: Accurately weigh 10 mg Tanshinone IIA, 84 mg glyceryl monostearate, 5 mg polyethylene glycol monostearate, 0.5 mg monoamino terminal Polyethylene glycol stearate, 99.5mg in total, was dissolved in 0.5mL ethanol as the organic phase, heated in a water bath at 60°C to completely melt the material, and deionized water was used as the dispersion medium, and the organic phase was sequentially mixed at a stirring speed of 400rpm Quickly inject 9.5 mL of deionized water heated in a water bath at 60°C, take out after injection and stir for 30 s, and naturally cool to room temperature to prepare tanshinone IIA lipid nanoparticles. Add 0.1mg of N,N'-disuccinimidyl carbonate as catalyst, vortex for 1min to disperse evenly, incubate at room temperature for 3h, add 100μL VCAM-1 monoclonal antibody (5mg / mL), vortex for 1min to disperse evenly Continue to incubate the reaction at room temp...

Embodiment 2

[0045] Example 2: Preparation of VCAM-1 monoclonal antibody Tanshinone IIA lipid nanoparticles, accurately weighed 10mg Tanshinone IIA, 85mg glyceryl monostearate, 4mg polyethylene glycol monostearate, 0.5mg monoamino-terminated Polyethylene glycol stearate, 99.5mg in total, was dissolved in 0.5mL of ethanol as the organic phase, heated in a water bath at 60°C to completely melt the material, and deionized water was used as the dispersion medium, and the organic phase was rapidly mixed at a stirring speed of 400rpm. Inject into 9.5 mL of deionized water heated in a water bath at 60°C, take out after injection and stir for 30 s, and cool naturally to room temperature to prepare tanshinone IIA lipid nanoparticles. Add 0.1mg of N,N'-disuccinimidyl carbonate as catalyst, vortex for 1min to disperse evenly, incubate at room temperature for 3h, add 100μLVCAM-1 monoclonal antibody (5mg / mL), vortex for 1min to disperse evenly Continue to incubate the reaction at room temperature for 3...

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Abstract

The invention discloses a VCAM-1 monoclonal antibody tanshinone IIA nanostructure lipid carrier as well as a preparation method and application thereof. A VCAM-1 monoclonal antibody tanshinone IIA lipid nanoparticle is prepared from 10 parts by mass of tanshinone IIA, 84-89 parts by mass of glyceryl monostearate, 0-5 parts by mass of polyethylene glycol monostearate, 0.5 part by mass of monoaminoterminal polyethylene glycol stearate and 0.5 part by mass of a VCAM-1 monoclonal antibody. The VCAM-1 monoclonal antibody tanshinone IIA lipid nanoparticle provided by the invention can target inflammatory vascular endothelial cells, improves the distribution of drugs in lesion parts, and starts from targeted intervention of the vascular endothelial cells to realize complete and efficient targeted treatment of diabetic nephropathy.

Description

technical field [0001] The invention belongs to the field of research on new drug delivery systems, and in particular relates to a VCAM-1 monoclonal antibody tanshinone IIA lipid nanoparticle and a preparation method and application thereof. Background technique [0002] Diabetic nephropathy (DN) refers to the abnormality of kidney structure, function or clinical indicators caused by diabetes. It is one of the most common complications of diabetes and the main cause of end-stage renal failure (ESRD). According to the latest research, it is estimated that there will be 550 million diabetic patients in the world by 2030, and 30% to 50% of diabetic patients will further develop DN. The pathological features of DN are mainly glomerular hypertrophy, basement membrane thickening and matrix deposition in the mesangial area. In the late stage, glomerulosclerosis and interstitial fibrosis appear, and even enter the uremia stage. So far, the clinical treatment for DN is mainly the co...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/68A61K31/58A61K47/14A61K47/18A61P13/12A61P3/10
CPCA61K47/6801A61K31/58A61K47/14A61K47/18A61P13/12A61P3/10
Inventor 汪一帆应栩华陈观平李明乾胡静波
Owner TONGDE HOSPITAL OF ZHEJIANG PROVINCE