Preparation method of sanguinarine liposome with acid sensitivity

A technology of sanguinarine liposomes and plastids, applied in the field of preparation of sanguinarine liposomes, can solve the problems of loss of anticancer drugs, lack of targeting and immunogenicity, etc., achieve simple preparation process, improve in vivo and in vitro inhibition The effect of tumor rate and high encapsulation rate

Inactive Publication Date: 2012-06-27
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Although liposomes have a series of advantages such as reducing the systemic toxic and side effects of anticancer drugs and improving the curative effect, they also have many problems such as being easily cleared by the RES system, insufficient targeting, and immunogenicity.
One of them is that most common liposomes enter cells by endocytosis, first exist in the endosome (endosome), and then are transported to the lysosome (lysosome) under the mediation of the microtubule system. In the enzyme body, liposomes and the active ingredients contained in them are degraded, which directly leads to the loss of anticancer drugs

Method used

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  • Preparation method of sanguinarine liposome with acid sensitivity
  • Preparation method of sanguinarine liposome with acid sensitivity
  • Preparation method of sanguinarine liposome with acid sensitivity

Examples

Experimental program
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Effect test

Embodiment 1

[0054] Take by weighing 1.6g soybean lecithin (purity is greater than 99% phosphatidylcholine), 160mg cholesterol is dissolved in 50mL ethanol, ultrasonic, dissolve; / L). The mixed solution was rotary evaporated at 50° C. for 2 h, and the ethanol was completely evaporated to dryness, and homogenized under high pressure to reduce the particle size (5000 psi, 3 times), to obtain blank liposomes before drug loading. Then the blank liposomes were placed in a dialysis bag, the two ends were tied tightly, put into 500 mL of normal saline for 2 hours, and the normal saline was changed every hour. Finally, dissolve 90 mg of sanguinarine in 90 mL of distilled water, mix it with the above-mentioned liposomes after dialysis, incubate in a water bath at 30°C for 5 min, and after sterile filtration (the pore size of the membrane filter is 0.2 μm), divide the subsequent filtrate into vials That's it. The molar ratio of sanguinarine: soybean lecithin: cholesterol is 1:7.5:1.5.

[0055] Th...

Embodiment 2

[0060] It is basically the same as Example 1, but there are the following changes: when preparing blank liposomes in the early stage, the operation process is: take 1g of soybean phospholipid (purity greater than 99% phosphatidylcholine), dissolve 160mg of cholesterol in 50mL of ether, ultrasonically, Dissolving; under the condition of 300rpm magnetic stirring, slowly inject the above solution into 30mL of ammonium citrate solution (300mmol / L), and the mixed solution was rotatated at 50°C for 2h, and the ether was completely evaporated to dryness, and the water bath was sonicated to reduce the particle size to obtain Blank liposomes before drug loading. Then the blank liposomes were placed in a dialysis bag, the two ends were tied tightly, put into 500 mL of normal saline for 2 hours, and the normal saline was changed every hour. Afterwards, the sanguinarine aqueous solution prepared in Example 1 was mixed with the above solution, incubated in a water bath at 30°C for 5 minute...

Embodiment 3

[0063] Take by weighing 1.6g soybean lecithin (purity is greater than 99%), 160mg cholesterol is dissolved in the dichloromethane, this solution is placed in the eggplant shape bottle of grind mouth, removes organic solvent under reduced pressure on 30 ℃ constant temperature water baths, makes phospholipid, Cholesterol forms a uniform film on the bottom of the bottle, and then put it in a vacuum desiccator to vacuum overnight, and set aside. In addition, 30 mL of 300 mmol / L ammonium citrate solution was added to the above-mentioned eggplant-shaped bottle, and the membrane was washed by rotating at 30° C. until milky white liposome suspension was formed, homogenized under high pressure to reduce the particle size (5000 psi, 3 times), to obtain blank liposomes before drug loading. Then the blank liposomes were placed in a dialysis bag, the two ends were tied tightly, put into 500 mL of normal saline for 2 hours, and the normal saline was changed every hour. Mix the sanguinarine...

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Abstract

The invention relates to the field of pharmaceutical preparation, in particular to a preparation method of sanguinarine liposome with acid sensitivity, which is characterized by selecting citric acid ammonium salt for preparing the sanguinarine liposome when an ammonium salt gradient method is adopted for preparation. The sanguinarine liposome prepared by the method of the invention has acid sensitivity and is favorable to the antitumor effect.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a method for preparing sanguinarine liposomes, and the sanguinarine liposomes prepared by the method of the invention have acid sensitivity. Background technique [0002] Sanguinarine was discovered in the early 19th century, and its molecular formula is C 20 h 14 NO 4 , with a relative molecular mass of 332. As a benylisoquinoline alkaloid, it has a wide range of antibacterial, antifungal and antiinfective properties. Recent studies have shown that sanguinarine has good inhibitory activity on a variety of human cancer cells. It can reduce the proliferation of blood vessels around cancer cells by inhibiting endothelial growth factor, and can inhibit the growth of cancer cells without affecting normal cells at micromolar concentrations. It can effectively block the MDR (multidrug resistance effect) of most tumor cells, so it is expected to play a role in clinical tum...

Claims

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Application Information

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Patent Type & AuthorityPatents(China)
IPC IPC(8): A61K9/127A61K31/4741A61K47/12A61P35/00
Inventor柯学贝俊宏董晓卉邱黎娜栗婕
OwnerCHINA PHARM UNIV