Preparation method of triptolide and berberine co-loaded nano-liposome with brain targeting function

A technology of triptolide and nano-liposomes, which is applied in the field of medicine, can solve the problems of limited clinical application, the course of AD cannot be effectively blocked, and adverse reactions, so as to improve brain targeting and prolong circulation time in the body , Improve the effect of anti-AD drug effect

Pending Publication Date: 2022-04-05
THE SECOND PEOPLES HOSPITAL OF SHENZHEN +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, TP is distributed in the digestive, circulatory, blood and other systems and multiple organs, and has obvious toxic and side effects on the immune system, blood system, digestive system, heart, liver, and kidney, and will cause serious adverse reactions, which severely affects the use of TP. In clinical application, its wide distribution in the body reduces the drug concentration and bioavailability in the brain; BR is difficult to absorb when taken orally, and the bioavailability is extremely low. Produce toxic effects such as myocardial toxicity, these problems seriously restrict its application in the clinical treatment of AD
[0005] To sum up, the problems existing in the prior art are: the course of AD cannot be effectively blocked at present, the existing therapeutic drugs can only temporarily alleviate the symptoms of AD, and have large side effects, and there is a large risk in the treatment of a single target. limitation
TP and BR are widely distributed in the body, resulting in multi-organ toxicity, extremely low bioavailability, and few drugs reaching the brain, which limits their clinical application

Method used

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  • Preparation method of triptolide and berberine co-loaded nano-liposome with brain targeting function
  • Preparation method of triptolide and berberine co-loaded nano-liposome with brain targeting function
  • Preparation method of triptolide and berberine co-loaded nano-liposome with brain targeting function

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preparation example Construction

[0087] The embodiment of the present invention provides a method for preparing triptolide and berberine co-loaded stealth nanoliposome TP-BR-PL, including: selecting the improved ethanol injection method using citric acid as the hydration medium; HSPC / CH ratio 3:1; ethanol 10% (v / v); mPEG 2000 -DSPE / DSPE-PEG 2000 -COOH ratio is 1:2; 65°C water bath stirring for 20min; BR drug loading temperature is 55°C, drug loading time is 15min, drug-lipid ratio is 1:20; TP drug loading temperature is 50°C, drug loading time is 1h.

[0088] The preparation method of triptolide and berberine co-loaded stealth nano-liposome TP-BR-PL uses citric acid as the hydration medium to prepare PEGylated blank liposome PL and carboxy-terminal PL -COOH; sodium phosphate to adjust the pH of the external aqueous phase to establish a gradient method to prepare berberine PEGylated liposomes BR-PL and BR-PL-COOH; passive drug loading method, mechanical stirring loading TP, preparation of triptolide and small...

Embodiment 1

[0110] Materials and Instruments: Triptolide (TP, purity > 98%, PI & PI Biotechnology Co., Ltd.); Berberine hydrochloride (content > 98%, Shanghai Tongtian Biotechnology Co., Ltd.); hydrogenated soybean lecithin (HSPC, Germany Lucas Meyer company); Cholesterol (CH, Nanjing Xinbai Pharmaceutical Co., Ltd.); polyethylene glycol monomethyl ether 2000-distearoylphosphatidylethanolamine (mPEG2000-DSPE, American Genzyme Company); distearoylphosphatidylethanolamine-polyethylene glycol Alcohol 2000-carboxyl conjugate (DSPE-PEG2000-COOH, Aiweituo Pharmaceutical Technology Co., Ltd.); Lactoferrin (Lf, Japan Wako Pure Pharmaceutical Co., Ltd.); Methanol (chromatographically pure, Shandong Yuwang Industrial Co., Ltd. chemical fraction company); 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC HCl, Sigma Corporation, USA); N-hydroxysuccinimide (NHS, Sigma Corporation, USA) Triethylamine (TEA, Tianjin Bodi Chemical Co., Ltd.); Phosphoric acid (analytical grade, Tianjin Dam...

Embodiment 2

[0168] Effects of TP-BR-Lf Nanoliposomes on the Behavioral Ability of AD Model Mice

[0169] 2.1.1 Y maze experiment

[0170] method:

[0171] The effect of TP-BR-Lf nanoliposomes on the behavioral ability of AD model mice was detected by Y maze experiment. The mice were divided into 5 groups, namely blank control group, model group, TP-Lf, BR-Lf and TP-BR-Lf groups, with 9 mice in each group (n=9). After the successful establishment of the AD mouse model induced by intracerebroventricular injection of Aβ1-42, each group began to inject into the tail vein, the concentration of BR was 10 mg / Kg, once every other day, a total of 7 times.

[0172] The procedure of Y maze experiment is the same as 2.3.1. During the experiment, the excrement was cleaned up in time to eliminate the remaining smell. The spatial working memory ability of mice was reflected by the spontaneous alternation response rate (alternation behavior %), which was calculated according to the following formul...

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Abstract

The embodiment of the invention discloses a preparation method of a triptolide and berberine co-loaded invisible nano-liposome. The preparation method comprises the following steps: preparing a PEGylated blank liposome PL and a carboxyl-end blank liposome PL-COOH by taking citric acid as a hydration medium and adopting an improved ethanol injection method; adjusting the pH value of the carboxyl-terminal blank liposome PL-COOH to 7 by using hydrochloric acid, taking the gradient PEGylated blank liposome PL, and adding the gradient PEGylated blank liposome PL into a berberine hydrochloride BR solution according to a drug-lipid ratio of 1: (15-25) to obtain BR-PL and BR-PL-COOH liposome; the preparation method comprises the following steps: adding a triptolide TP solution into BR-PL and BR-PL-COOH lipidosome, incubating for at least 60 minutes at a constant temperature of 40-60 DEG C, and terminating drug loading in an ice-water bath, so as to prepare the triptolide and berberine co-loaded invisible nano-lipidosome TP-BR-PL and TP-BR-PL-COOH.

Description

technical field [0001] The embodiment of the present invention relates to the technical field of medicine, especially a preparation method of stealth triptolide and berberine co-loaded nano liposomes with brain targeting function. Background technique [0002] Alzheimer's disease (AD) is the most common senile dementia, characterized by progressive cognitive decline and frequent neurological syndromes, with an increasingly younger age of onset. More than 50 million people worldwide live with dementia, costing as much as $1 trillion annually. AD has become a major public health problem that imposes a heavy burden on patients' families and society. At present, the clinical treatment drugs for AD are mainly palliative and symptomatic cholinesterase inhibitors and glutamate receptor antagonists, which can only temporarily relieve clinical symptoms, but cannot delay or block the pathological process of AD, and have many side effects and adverse reactions. . Therefore, there is...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/585A61K31/4375A61K9/127A61K47/42A61K47/24A61P25/28
Inventor 吴正治王林李映红李芷悦李利民刘展艳刘洁人李子雯
Owner THE SECOND PEOPLES HOSPITAL OF SHENZHEN
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