Berberine long-circulating nano-liposome with brain targeting function and preparation method of berberine long-circulating nano-liposome

A nano-liposome and berberine technology, applied in the field of medicine, can solve the problems of large side effects and limited clinical application

Inactive Publication Date: 2021-11-26
SHENZHEN ELDERLY MEDICAL RES INST +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The course of AD cannot be effectively blocked at present, and the existing therapeutic drugs can only temporarily relieve the symptoms of AD, and the side effects are large; in the prior art, there is no combination of natural Chinese medicine active ingredient berberine and modern advanced drug-loading technology to prepare a drug with brain function. Targeted stealth nano-liposomes are used in the prevention and treatment of AD; BR is widely distributed in the body, causing multi-organ toxicity, and few drugs reach the brain, which limits its clinical application

Method used

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  • Berberine long-circulating nano-liposome with brain targeting function and preparation method of berberine long-circulating nano-liposome
  • Berberine long-circulating nano-liposome with brain targeting function and preparation method of berberine long-circulating nano-liposome
  • Berberine long-circulating nano-liposome with brain targeting function and preparation method of berberine long-circulating nano-liposome

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Experimental program
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preparation example Construction

[0056] Such as figure 1 Shown, a kind of preparation method of berberine long circulation nanoliposome BR-Lf with brain targeting function, comprising:

[0057] S110, using ammonium sulfate as a hydration medium, and preparing blank liposome PL-COOH containing antelope base end by a modified ethanol injection method;

[0058] S120. Take 2 parts by mass of PL-COOH liposomes, add 1 part by mass of EDC aqueous solution and 1 mass part of NHS aqueous solution in an ice-water bath, activate with magnetic stirring for 0.5h, return to room temperature, and add 6 parts by mass of PL-COOH liposome After the lactoferrin Lf is fully dissolved, add 1.4 parts by mass of TEA, react for at least 4 hours, and then stop the reaction in an ice-water bath to obtain lactoferrin-modified PEGylated blank liposomes PL-Lf;

[0059]S130. Take the PL-Lf suspension, remove the external water phase through an anion-cation fiber column, add berberine hydrochloride BR solution according to the ratio of dr...

Embodiment 1

[0061] The berberine long-circulation nanoliposome BR-PL uses nanoliposome as drug carrier and is prepared by stealth modification with polyethylene glycol PEG.

[0062] PEGylated blank liposomes PL and carboxy-terminal PL-COOH were prepared by using ammonium sulfate as the hydration medium by the modified ethanol injection method, and berberine PEGylated liposomes BR-PL and BR-PL-COOH were prepared by the ammonium sulfate gradient method. Among them, specifically include:

[0063] Using ammonium sulfate as the hydration medium, blank liposomes were prepared by the modified ethanol injection method. Accurately weigh and take the prescribed amount of film material into the vial, the ratio of HSPC / CH is 3:1, mPEG 2000 -DSPE / DSPE-PEG 2000 -COOH ratio is 1:2, mixed with ethanol 10% (v / v), heated in water bath at 65°C, (NH 4 ) 2 SO 4 The concentration of the solution was 200mM, and the mixture was stirred in a water bath for 20 minutes to obtain the primary blank liposome.

...

Embodiment 2

[0067] Brain-targeted berberine long-circulation nanoliposome BR-Lf is prepared by covalently coupling brain-targeted ligand Lf to the surface of carboxy-terminal PEGylated BR liposomes, including:

[0068] Using ammonium sulfate as the hydration medium, PL-COOH containing carboxy-terminal blank liposomes was prepared by the modified ethanol injection method. Accurately weigh and take the prescribed amount of film materials into the vials, the ratio of HSPC / CH is 3:1, the ratio of mPEG2000-DSPE / DSPE-PEG2000-COOH is 1:2, mixed with ethanol 10% (v / v), 65 ℃ water bath, evaporate most of the ethanol, add 200mM (NH 4 ) 2 SO 4 The solution was 3 mL, stirred in a water bath for 20 min, and the primary blank liposome was obtained.

[0069] After treatment with an ultrasonic cell pulverizer (200W×2min, 400W×6min, working for 1s, intermittent for 1s), pass through 0.8μm, 0.45μm, and 0.22μm microporous membranes in turn for sizing to obtain carboxy-terminal PL-COOH.

[0070] Precisel...

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Abstract

The invention belongs to the technical field of medicine and pharmacology, and discloses a preparation method of berberine long-circulating nano-liposome BR-Lf with a brain targeting function. The preparation method comprises the following steps: preparing a PL-COOH liposome by using ammonium sulfate as a hydration medium and adopting an improved ethanol injection method; taking 2 parts by mass of PL-COOH, adding 1 part by mass of an EDC solution and 1 part by mass of an NHS solution in an ice-water bath, performing magnetic stirring and activating for 0.5 h, restoring to room temperature, adding 6 parts by mass of Lf, performing full dissolving, adding 1.4 parts by mass of TEA, performing reacting for 4 h, and terminating the reaction in the ice-water bath to obtain lactoferrin modified PEGylated blank liposome PL-Lf; and taking PL-Lf suspension, removing an external water phase through an anion-cation fiber column, adding a berberine hydrochloride BR solution according to a drug-lipid ratio of 1: 15, performing incubating at a constant temperature of 40 DEG C for at least 15 minutes, and terminating drug loading in the ice-water bath to obtain BR-Lf. By optimizing the preparation process, the BR-Lf which is uniform in particle size distribution, relatively high in encapsulation efficiency and good in stability is successfully prepared.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a berberine long-circulation nano-liposome with brain-targeting function and a preparation method thereof. Background technique [0002] Alzheimer's disease (AD) is the most common senile dementia, a degenerative disease of the central nervous system, characterized by progressive memory loss, cognitive impairment, and personality changes, and mostly occurs in old age or pre-senile. According to the World Alzheimer Report 2019, more than 50 million people worldwide are living with dementia, and this number will increase to 152 million by 2050. One person develops dementia every 3 seconds, and the annual dementia cost is currently estimated at $1 trillion and will double by 2030. AD has become one of the greatest global public health and social care challenges facing humanity today and in the future. At present, the clinical treatment drugs for Alzheimer's disease a...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/10A61K47/42A61K31/4375A61P25/28G01N30/02G01N21/33
Inventor 吴正治王林姜倩倩乐卫东汪梦霞张淼刘洁人李利民李子雯
Owner SHENZHEN ELDERLY MEDICAL RES INST
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