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Phospholipid chitosan drug delivery system, preparation method and uses thereof

A delivery system, chitosan technology, applied in the digestive system, nano-drugs, drug combinations, etc., can solve the problems of drug leakage, inability to obtain encapsulation rate, and encapsulation rate of only 52.4±2.4%

Active Publication Date: 2017-11-03
BEIJING WEHAND BIO PHARMA CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Some medicines with low fat solubility can also be made into phospholipid / chitosan nanoparticles with higher encapsulation efficiency, for example, Renu Chadha et al. [Renu Chadha, et al., Journal of Microencapsulation, 2012,29 (8): 805-812] prepared phospholipid / chitosan nanoparticles of hydrochlorothiazide, with an encapsulation efficiency of 81.8±1.7%; Marthyna P.Souza et al. -1159] prepared phospholipid / chitosan nanoparticles of quercetin with an encapsulation efficiency of 96.13±0.44%; however, some highly fat-soluble drugs cannot obtain phospholipid / chitosan nanoparticles with high encapsulation efficiency. For example, the phospholipid / chitosan nanoparticles of β-lapachone prepared by Esther Moreno et al. [Esther Moreno, et al., Nanomedicine Nanotechnology Biology & Medicine, 2015,11(8):2003-2012], the encapsulation efficiency is only 52.4± 2.4%
Especially some drugs with polar groups such as amino group, hydroxyl group, carbonyl group, carboxyl group, amide group, ester group, etc., may have low encapsulation efficiency, drug leakage, particle size, Zeta potential and other changes and become unstable , for example, R.S.Bhatta et al. [R.S.Bhatta, et al., International Journal of Pharmaceutics, 2012, 432 (1-2): 105-112] prepared natamycin (with hydroxyl, amino, carboxyl, ester group) The encapsulation efficiency of phospholipid / chitosan nanoparticles was 73.57±0.62%. When stored at 4°C for 60 days, the encapsulation efficiency decreased significantly, and natamycin leaked seriously

Method used

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  • Phospholipid chitosan drug delivery system, preparation method and uses thereof
  • Phospholipid chitosan drug delivery system, preparation method and uses thereof
  • Phospholipid chitosan drug delivery system, preparation method and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] 1. Preparation of baicalein-lipid complex

[0055] (1) Preparation of baicalein lipid complex I (baicalein: soybean lecithin (w / w)=1:3.5)

[0056] Take 1g of baicalein, 3.5g of soybean lecithin, add 40mL of tetrahydrofuran, compound at 40°C for 1 hour, remove the solvent by rotary evaporation, and dry in vacuum for more than 12 hours (20-30°C) to obtain baicalein lipid complex I, airtight Pack and store in the refrigerator.

[0057] (2) Preparation of baicalein lipid complex II (baicalein: soybean lecithin (w / w)=1:6)

[0058] Take 0.5g of baicalein and 3.0g of soybean lecithin, add 40mL of ethyl acetate, compound at 40°C for 1 hour, remove the solvent by rotary evaporation, and dry in vacuum for more than 12 hours (20-30°C) to obtain the baicalein lipid complex II, airtightly packaged and stored in the refrigerator.

[0059] 2. Preparation of baicalein lipoplex I-phospholipid / chitosan drug delivery system

[0060] (1) Dissolve low, medium and high viscosity chitosan...

Embodiment 2

[0072] 1. Preparation of paclitaxel lipoplex

[0073] (1) Preparation of paclitaxel lipoplex I (paclitaxel: egg yolk phospholipid (w / w)=1:6)

[0074] Take paclitaxel 0.5g, egg yolk phospholipid 3.0g, add tetrahydrofuran 100mL, compound at 40°C for 1 hour, remove the solvent by rotary evaporation, and dry in vacuum for more than 12 hours (20-30°C) to obtain paclitaxel lipid complex I, sealed package , stored in the refrigerator.

[0075] (2) Preparation of Paclitaxel Lipid Complex II (Paclitaxel:Cholesterol (w / w)=1:2)

[0076] Take 0.5g of paclitaxel and 1.0g of cholesterol, add 200mL of acetone preheated to 40°C, compound at 40°C for 2 hours, remove the solvent by rotary evaporation, and dry in vacuum for more than 12 hours (20-30°C) to obtain paclitaxel lipid compound Material II, airtightly packaged, stored in the refrigerator.

[0077] 2. Preparation of paclitaxel lipoplex II-phospholipid / chitosan drug delivery system

[0078] (1) low-viscosity chitosan is dissolved in ...

Embodiment 3

[0090] 1. Preparation of Chlorogenic Acid Lipid Complex

[0091] (1) Preparation of chlorogenic acid lipid complex I (chlorogenic acid: soybean lecithin (w / w)=1:2.5)

[0092] Take 0.5g of chlorogenic acid and 1.25g of soybean lecithin, add 50mL of absolute ethanol, compound at 40°C for 30 minutes, remove the solvent by rotary evaporation, and dry in vacuum for more than 12 hours (20-30°C) to obtain chlorogenic acid lipid compound Thing I, airtightly packaged, puts into the refrigerator for refrigerated preservation.

[0093] (2) Preparation of chlorogenic acid lipid complex II (chlorogenic acid:distearoylphosphatidylcholine (w / w)=1:2.2)

[0094] Take 1g of chlorogenic acid and 2.2g of distearoylphosphatidylcholine, add 50mL of absolute ethanol, compound at 40°C for 30 minutes, remove the solvent by rotary evaporation, and dry in vacuum for more than 12 hours (20-30°C), to obtain green Ortho-acid lipid complex II, airtightly packaged, stored in the refrigerator.

[0095] 2. ...

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Abstract

The invention relates to a phospholipid chitosan drug delivery system, a preparation method and uses thereof, wherein the phospholipid chitosan drug delivery system comprises a drug-lipid complex and chitosan, the phospholipid in the phospholipid chitosan drug delivery system is derived from free phospholipid and / or the phospholipid in a lipid complex, and the drug in the drug-lipid complex does not contain insulin. The drug delivery system of the present invention can be used for oral administration systems, transdermal administration systems, mucosal administration systems, pulmonary inhalation administration systems and other administration systems.

Description

technical field [0001] The invention relates to a novel phospholipid / chitosan drug delivery system and its preparation method and application. Background technique [0002] Phospholipid / chitosan nanoparticles (Lecithin / chitosannanoparticles, LCNs) is a kind of nanoparticle discovered by Italian scholar F.Sonvico et al. [Sonvico F.et al., Int J Pharm,2006,324:67-73] in 2006. Carrier, which is formed by self-assembly of negatively charged phospholipids and positively charged chitosan through charge interaction under certain conditions. [0003] Phospholipid / chitosan nanoparticles have attracted extensive attention from scholars at home and abroad in recent years due to their good biocompatibility, biodegradability, and bioadhesion. And so on, and its application in the food field has been in-depth research. [0004] According to Sonvico F. et al. report, phospholipid / chitosan nanoparticles are suitable for encapsulating lipophilic drugs. However, whether the drug is suitabl...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K31/352A61K31/337A61K31/57A61K31/216A61K47/24A61K47/36
CPCA61K9/5123A61K9/5161A61K31/216A61K31/337A61K31/352A61K31/57A61K9/5192A61K9/127A61K47/24A61K47/28A61K45/00A61P31/04A61P31/10A61P31/12A61P29/00A61P43/00A61P37/02A61P39/06A61P17/18A61P17/16A61P35/00A61P5/00A61P9/12A61P3/06A61P9/10A61P31/14A61P19/10A61P1/16B82Y5/00B82Y40/00A61K47/36A61K9/51
Inventor 刘玉玲王玮珏董武军郝华珍夏学军黄岳升金毅群蒋玲敏周君卓
Owner BEIJING WEHAND BIO PHARMA CO LTD
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