Natural nanoparticle-medicine composition for resisting Alzheimer's disease and preparation method and application thereof

An Alzheimer's disease, nanoparticle technology, applied in drug combination, nanomedicine, nanotechnology for materials and surface science, etc., can solve the problems of limited source of raw materials, limited source of raw materials, complicated preparation process, etc. Wide application prospects and the effect of solving delivery difficulties

Active Publication Date: 2018-10-23
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The preparation method of recombinant lipoprotein has been reported in literature and patents, but there are problems such as limited source of raw materials, complicated preparation process, and inability to simulate endogenous lipoprotein well.
CN 104324007A discloses a preparation technology and application of natural lipid nanoparticles, specifically extracting apolipoprotein and phospholipid from plasma fraction IV and recombining with anti-tumor drugs in vitro to prepare highly efficient tumor-targeting nanoparticles. Large-scale production, but the source of raw materials for this method is relatively limited, and the purity of the extracted lipoproteins is not high. At the same time, it is used for the delivery of anti-tumor drugs. How to extract high-purity lipoproteins, expand the source of raw materials and realize the application of anti-Alzheimer's disease needs to be improved
CN 104138595 A discloses the preparation of a bionic recombinant high-density lipoprotein and its application in the prevention and treatment of Alzheimer's disease. It uses in vitro lipid and apolipoprotein recombination to construct recombinant high-density lipoprotein, and realizes targeted removal of Aβ to treat AD , but the lipoprotein composition involved in this method is only high-density lipoprotein and its composition is not exactly the same as that of natural lipoprotein, which cannot reproduce the physiological function of natural lipoprotein well. At the same time, the recombinant high-density lipoprotein does not serve as a Targeted drug carrier solves the problem of targeted drug delivery in AD brain
Therefore, how to prepare recombinant lipoproteins that highly restore the physiological functions of endogenous lipoproteins and efficiently carry drugs to achieve brain-targeted delivery has not yet been reported.

Method used

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  • Natural nanoparticle-medicine composition for resisting Alzheimer's disease and preparation method and application thereof
  • Natural nanoparticle-medicine composition for resisting Alzheimer's disease and preparation method and application thereof
  • Natural nanoparticle-medicine composition for resisting Alzheimer's disease and preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1

[0048] Embodiment 1: the preparation process of the natural nanoparticle-pharmaceutical composition of anti-Alzheimer's disease:

[0049] 1.1 Preparation of natural nanoparticles-drug composition loaded with donepezil by ultrasonic drug loading method

[0050]

[0051]

[0052] (1) if figure 1 As shown, the natural nanoparticle-drug composition loaded with donepezil was prepared according to the ultrasonic drug loading method. Weigh 10 mg of natural nanoparticle-high-density lipoprotein of prescription quantity and disperse in ultrapure water to form natural high-density lipoprotein nanoparticle suspension;

[0053] (2) Dissolve 5 mg of the prescription amount of donepezil in ethanol and add dropwise to the natural nanoparticle suspension described in (1), place the probe in an ice bath for ultrasonic dispersion for 60 min;

[0054] (3) After the sonication, the drug solvent ethanol was removed by rotary steaming at 37°C for 20 minutes under reduced pressure, then pass...

Embodiment 2

[0150] Embodiment 2: the property investigation of anti-Alzheimer's disease natural nanoparticle-drug composition:

[0151] 2.1 The natural nanoparticle-medicine composition loaded with donepezil prepared according to Example 1.1, and characterize its particle size and carry out morphological investigation: the particle diameter of the natural nanoparticle-medicine composition measured by dynamic light scattering method is (65.8 ± 4.45) nm, showing a spherical appearance under the transmission electron microscope ( figure 2 ), and consistent with the particle size measured by the laser particle size analyzer.

[0152] 2.2 Investigation of the encapsulation efficiency and drug loading capacity of the natural nanoparticle-drug composition loaded with donepezil prepared according to Example 1.1: Measure 200 μL of the natural nanoparticle-drug composition loaded with donepezil into a 10 mL volumetric flask, add methanol to volume To the scale, ultrasonically in a water bath for ...

Embodiment 3

[0154] Embodiment 3: According to the natural nanoparticle-pharmaceutical composition loaded with donepezil prepared in Example 1.1: the in vitro BBB model is constructed by Transwell co-cultivation, and human-derived brain microvascular endothelial cells (hCMEC / D3) are inoculated in the upper chamber of Transwell (6× 10 5 cells / cm 2 ), mouse microglial cells (BV-2) were inoculated in the lower chamber of Transwell (2×10 5 cells / cm 2 ), the cell transmembrane resistance was measured by a transmembrane resistance meter. On the seventh day of co-culture, the transmembrane resistance value was as high as 200Ω / cm 2 , which proves that the Transwell BBB model has been constructed successfully. The fluorescent dye coumarin 6 (C6) was used to replace the drug, and the C6-labeled natural nanoparticle-drug composition and liposome were respectively constructed. Add 200 μL of C6-labeled natural nanoparticle-pharmaceutical composition and liposome to the upper chamber of the Transwe...

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Abstract

The invention belongs to the field of medicine preparations and particularly relates to a natural nanoparticle-medicine composition for resisting Alzheimer's disease (AD) and a preparation method, property evaluation and application thereof. By recombining extracted natural lipoprotein nanoparticles and AD treatment medicine to prepare the natural nanoparticle-medicine composition, combined treatment of AD is achieved. The combined treatment is high in homologous bionic performance and safety, high in medicine loading capacity, efficient in brain targeting, high in amyloid protein affinity, capable of achieving targeting removing, mild in preparation conditions, simple in preparation process and easy in industry expanding. The natural nanoparticle-medicine composition is administrated through intravenous injection, oral taking, nasal delivery and the like, a new thought and technology is provided for the research and development of new AD medicine, and the natural nanoparticle-medicinecomposition has an important research value and promising clinical research prospect.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to the preparation and application of an anti-Alzheimer's disease natural nanoparticle-medicine composition. Background technique [0002] Alzheimer's disease (AD), also known as senile dementia, is a degenerative disease of the central nervous system characterized by progressive cognitive impairment and memory loss. With the development of the global aging process, the incidence of AD continues to increase and seriously affects human health and quality of life. The "World Alzheimer's Disease Report" pointed out that the number of dementia patients is expected to double every 20 years, and, by The number of patients will exceed 100 million in 2050. Therefore, Alzheimer's disease has become a major public health issue and an increasingly prominent social problem of common concern in all countries in the world. [0003] However, there is still a lack of effectiv...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/42A61K47/28A61K45/00A61K31/445A61K31/12A61K31/4748A61K31/7105A61K31/13A61K31/5415A61K38/08A61P25/28
CPCA61K9/5123A61K9/5169A61K31/12A61K31/13A61K31/445A61K31/4748A61K31/5415A61K31/7105A61K38/08A61K45/00A61P25/28A61K9/0019A61P25/00B82Y5/00B82Y30/00B82Y40/00
Inventor 周建平丁杨张华清
Owner CHINA PHARM UNIV
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