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Glutaryl cholesterol and liposome thereof and application of liposome as vaccine adjuvant

A technology of glutaryl cholesterol and vaccine adjuvant, which is applied in the directions of liposome delivery, medical preparations containing inactive ingredients, and medical preparations containing active ingredients, etc. Complex production process and other issues

Inactive Publication Date: 2013-12-18
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these methods cannot solve the problems of complex production process, high storage conditions and low vaccine encapsulation efficiency.

Method used

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  • Glutaryl cholesterol and liposome thereof and application of liposome as vaccine adjuvant
  • Glutaryl cholesterol and liposome thereof and application of liposome as vaccine adjuvant
  • Glutaryl cholesterol and liposome thereof and application of liposome as vaccine adjuvant

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Synthetic method of glutaryl cholesterol

[0028] 1. Add 300mg (3mmol) of glutaric anhydride, 290mg (0.75mmol) of cholesterol, 351mg (1.5mmol) of DMAP into a 100ml eggplant-shaped bottle, and add an appropriate amount of CH 2 Cl 2 Dissolve, reflux and stir in a water bath at 75°C for 96 hours, and filter to obtain glutaryl cholesterol.

[0029] 2. Put the above product in a clean separatory funnel, wash the above product three times with HCl, three times with saturated brine, and add dried Na 2 SO 4 Absorb water, stand still, and filter with suction.

[0030] 3. The product was washed again with dichloromethane, and the filtrates were combined, rotary evaporated, and suction filtered to obtain a purified product.

[0031] 4. Using petroleum ether: ethyl acetate: methanol (2:1:0.1) as a developing solvent and 20% ethanol-sulfuric acid as a developing reagent, the product was detected by TLC.

[0032] 5. The purified product is weighed, and the yield and purity are c...

Embodiment 2

[0035] The preparation method of glutaryl liposome:

[0036] Accurately weigh 90 mg of soybean lecithin and 30 mg of glutaryl cholesterol, put them in a 250 ml eggplant-shaped bottle, add 3 ml of absolute ethanol to dissolve lecithin and cholesterol. Rotate at 37°C water bath temperature for 1 hour to evaporate the organic solvent, so that the lipid forms a uniform film on the wall of the vessel. Add 12ml of 5% mannitol as a hydration solution, wash the membrane by rotation at room temperature, and hydrate for 30 minutes. The hydrated suspension was sonicated in a water bath for 20 minutes to obtain liposomes with an average particle size of 180-230 nm.

Embodiment 3

[0038] Referring to the preparation method of Example 2, the difference is that the organic solvent used for dissolving lecithin and cholesterol is replaced by diethyl ether, and the volume of 5% mannitol in the hydration solution is increased to 15ml. The average particle diameter of the prepared liposome is 220-260nm.

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Abstract

The invention relates to the field of pharmaceutic preparation, and particularly discloses glutaryl cholesterol (I) and liposome thereof and application of the liposome as a vaccine adjuvant. The glutaryl cholesterol is used for preparing the liposome which can be used as a vaccine adjuvant, and a vaccine and the glutaryl liposome are mixed and incubated and then can be used clinically. The blank glutaryl-liposome and the vaccine can be respectively stored, and the vaccine solution and the blank glutaryl-liposome can be mixed, incubated and coupled at any time with the binding ratio of the vaccine being more than 85 percent. The C57L / J animal experiment research shows that when the glutaryl-liposome is coupled with protein vaccine or cell vaccine for use, the antibody titer level can be improved, and the immune response is enhanced.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to glutaryl cholesterol and a liposome prepared from glutaryl cholesterol, which can be used as a vaccine adjuvant. Background technique [0002] With the development of bioengineering technology, the safety of human vaccines has been greatly improved, but their immunogenicity is very weak, especially recombinant protein peptide vaccines and DNA vaccines. Therefore, immune adjuvants are needed to improve the effect of immune response, and traditional immune adjuvants have relatively large toxic and side effects. At present, it is urgent to develop safe and effective new immune adjuvants to improve the immune response effect of the new generation of vaccines. [0003] Liposomes are lipid bilayers formed by phospholipids dispersed in an aqueous phase, and the interior is a closed vesicle of the aqueous phase. Because the structure is similar to biofilm, it is also called ar...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J9/00A61K9/127A61K47/28A61K47/24A61K39/39
Inventor 平其能程娟
Owner CHINA PHARM UNIV
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