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A kind of Fe3O4 magnetic nimodipine liposome and preparation method thereof

A nimodipine lipid and liposome technology, which is applied in the directions of liposome delivery, pharmaceutical formulations, organic active ingredients, etc., can solve problems such as limiting the wide application of magnetic liposomes, reducing the relative space of drugs, and potential safety hazards. , to achieve the effect of high yield, high repeatability and high biocompatibility

Active Publication Date: 2019-02-22
南京恒舟科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] In clinical application, 30% ethanol solution of nimodipine is often used for injection administration, which often needs to be diluted during application, resulting in the precipitation of nimodipine, interruption of treatment, scrapping of drugs, and hidden dangers in safety, etc.
In addition, the current preparation of magnetic liposomes is mainly to encapsulate magnetic nanoparticles and drugs together in liposomes, resulting in smaller relative space for drugs and low encapsulation efficiency.
Moreover, encapsulating magnetic particles in liposomes has strict requirements on the size and properties of magnetic nanoparticles, which greatly limits the wide application of magnetic liposomes.

Method used

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  • A kind of Fe3O4 magnetic nimodipine liposome and preparation method thereof
  • A kind of Fe3O4 magnetic nimodipine liposome and preparation method thereof
  • A kind of Fe3O4 magnetic nimodipine liposome and preparation method thereof

Examples

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Effect test

Embodiment 1

[0022] Take 2 mg of nimodipine (purchased from Nanjing Zelang Biotechnology Co., Ltd.), 40 mg of soybean lecithin (purchased from Shenyang Tianfeng Biopharmaceutical Co., Ltd.) and 4 mg of cholesterol (purchased from Tianjin Damao Chemical Instrument Supply Station) and dissolve with magnetic stirring In 4mL of absolute ethanol, the lipid ethanol solution was obtained. Add the lipid ethanol solution dropwise into 8 mL of phosphate buffer solution (0.1M, pH 6.5), a hydration medium at 40°C, stir slowly with a magnetic stirrer during the dropping process, and remove absolute ethanol by rotary evaporation for 1 hour to obtain Nemo Dipin nanoliposome solution, stored at 4°C for later use;

[0023] FeSO 4 ·7H 2 O and FeCl 3 ·6H 2 O was dissolved in ultrapure water at a molar ratio of 1:2, 0.069 g of polyethylene glycol-2000 was added, and 1 mol / L NaOH solution was added dropwise in a 50°C water bath under ultrasonic until the pH of the solution was 11. Put the solution in a wa...

Embodiment 2

[0027] 2 mg of nimodipine, 50 mg of soybean lecithin and 10 mg of cholesterol were dissolved in 4 mL of absolute ethanol with magnetic stirring to obtain a lipid ethanol solution. Add the lipid ethanol solution dropwise into 10mL phosphate buffer (0.1M, pH 6.5) of the hydration medium at 45°C, stir slowly with a magnetic stirrer during the addition, and stir for 1.5h to remove absolute ethanol to obtain Ni Modipine nanoliposome solution, stored at 4°C for later use;

[0028] FeSO 4 ·7H 2 O and FeCl 3 ·6H 2 O was dissolved in ultrapure water at a molar ratio of 1:2. Add 0.110 g of polyethylene glycol-2000, and add 1 mol / L NaOH solution dropwise under ultrasound in a water bath at 50°C until the pH of the solution is 11. Put the solution in a water bath at 80°C to mature for 15 minutes, magnetically separate, wash with water and ethanol alternately until there is no Cl in the solution - , vacuum the solution at 50mT, freeze-dry at -103°C for 48h, and obtain 0.8g of solid p...

example 3

[0032] 2 mg of nimodipine, 60 mg of soybean lecithin and 16 mg of cholesterol were dissolved in 4 mL of absolute ethanol with magnetic stirring to obtain a lipid ethanol solution. Add the lipid ethanol solution dropwise into 12mL phosphate buffer solution (0.1M, pH6.5, ) of the hydration medium at 50°C, stir slowly with a magnetic stirrer during the dropwise addition, and stir for 2h to remove absolute ethanol to obtain Nemo Dipin nanoliposome solution, stored at 4°C for later use;

[0033] FeSO 4 ·7H 2 O and FeCl 3 ·6H 2 O was dissolved in ultrapure water at a molar ratio of 1:2. Add 0.15 g of polyethylene glycol-2000, and add 1 mol / L NaOH solution dropwise under ultrasound in a 50°C water bath until the pH of the solution is 12. Put the solution in a water bath at 80°C to mature for 15 minutes, magnetically separate, wash with water and ethanol alternately until there is no Cl in the solution - , the solution was vacuum-dried at 50mT, and freeze-dried at -103°C for 48h...

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Abstract

The invention discloses a Fe3O4 magnetic nimodipine liposome. The Fe3O4 magnetic nimodipine liposome is formed by combining polyethylene glycol-modified Fe3O4 nano particles onto the surface of a drug-carrying liposome, the diameter is about 100-200 nm, the morphology is regular, and black magnetic particles exist on the surface of the liposome to form the nano liposome which has the magnetic targeting property and can easily pass through a blood brain barrier. A preparation method of the magnetic liposome mainly comprises the steps that nimodipine, soybean lecithin and cholesterol are dissolved in ethyl alcohol, then the materials are added into a hydration medium phosphate buffer solution, absolute ethyl alcohol is removed through rotary evaporating or stirring, and then the nimodipine nano liposome is obtained; FeSO4.7H2O and FeCl3.6H2O are dissolved in ultrapure water according to the mole ratio of 1:2, polyethylene glycol-2000 is added, and polyethylene glycol-2000-modified Fe3O4 nano particles are prepared through a coprecipitation method; the liposome solution and a Fe3O4 aqueous solution are mixed according to a certain ratio, and then the Fe3O4 magnetic nimodipine liposome is obtained through incubation. According to the Fe3O4 magnetic nimodipine liposome and the preparation method thereof, operation is easy, the reaction is easy to control, the repeatability is high, and the yield is high.

Description

[0001] Technical Field The present invention relates to a drug magnetic liposome and a preparation method thereof. Background technique [0002] Parkinson's disease has become the third largest health killer of the elderly, and the trend of younger people is getting worse. Nimodipine is a dihydropyridine Ca 2+ Antagonists, which block Ca 2+ Enter cells, inhibit smooth muscle contraction and dilation of blood vessels, inhibit brain peroxidation, reduce the production of free radicals, thereby protecting brain neurons, and provide a new way of thinking for the prevention, treatment, and delay of Parkinson's disease. However, the extremely low solubility of nimodipine in water is not conducive to the absorption of the drug by the human body, and its bioavailability is low. Clinically, ethanol is used as a solvent to easily irritate blood vessels, which limits the full play of its pharmacological effects. Moreover, the tight connection between the blood-brain barrier epithelial ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K31/4422A61K47/10A61K47/02A61P25/16
CPCA61K9/127A61K31/4422A61K47/02A61K47/10
Inventor 高大威籍冰朔王美丽李磊邢珊珊
Owner 南京恒舟科技有限公司
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