A kind of liposome, its preparation method, liposome assembly and carrier liposome complex

A liposome and CH2 technology, applied in liposome delivery, drug combination, chemical instruments and methods, etc., can solve the problems of non-environmental stimuli responsiveness, poor repeatability, and low drug concentration, and achieve reliable Control the film forming temperature, broad application prospects, promote the effect of cell internalization

Active Publication Date: 2022-04-22
吉林省思睿德生物科技有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] (1) Targeted delivery problem: currently clinically used liposomes (represented by DPPC and DSPE liposomes) compound drugs mainly use the EPR effect of the tumor site for passive targeted enrichment
However, this passive targeting is not selective and is easily disturbed by the complex physiological environment
In addition, depending on the pure EPR effect, the drug concentration in the lesion is often low. In order to achieve effective treatment, it is necessary to increase the dosage, resulting in low drug utilization efficiency and side effects. In order to solve this problem, often Active targeting modification of common liposomes is required
[0004] (2) The problem of long circulation in the body: the liposome compound drugs currently used clinically are easily excreted out of the body by the endothelial reticulum system (RES) through the kidneys, liver, etc. during the blood circulation process, resulting in a short drug half-life, The problem of low drug utilization
Some commonly used methods for prolonging the metabolic half-life of liposome complex drugs, such as modifying polyethylene glycol (PEG) on the surface of liposomes, utilizing the anti-protein adsorption of PEG to prepare liposomes as "stealth liposomes" (stealthliposomes), although it will prolong the circulation of liposomes in the organism to a certain extent, but the repeatability is not good, and the problem of batch production needs to be solved urgently
[0005] (3) The chemical modifiability of liposomes: the liposomes currently used clinically are mainly natural soybean lecithin, egg yolk lecithin and artificially synthesized liposomes, and the main structures are long chain alkanes and phosphatidylcholine zwitterionic head group
In clinical treatment, traditional liposomes do not have environmental stimulus responsiveness (pH, oxygen partial pressure, magnetic field, ultrasound, light, enzyme, heat, etc.) due to the lack of effective chemical modification sites. Stimulus response), can only rely on the difference in drug concentration inside and outside the liposome cavity for release, and does not have controllable release

Method used

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  • A kind of liposome, its preparation method, liposome assembly and carrier liposome complex
  • A kind of liposome, its preparation method, liposome assembly and carrier liposome complex
  • A kind of liposome, its preparation method, liposome assembly and carrier liposome complex

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preparation example Construction

[0126] According to the present invention, the first preparation method of the liposome comprises the following steps:

[0127] a) compound A 1 -COOH, Compound A 2 -COOH is reacted with 1,2-propanediol derivative X-1 to obtain compound Y-1;

[0128] b) reacting the phosphinocyclopentane compound X-2 with the dimethylamine compound X-3 to obtain the compound Y-2;

[0129] c) reacting the compound Y-1 with the compound Y-2 to obtain liposomes represented by formula (I);

[0130] The steps a) and b) have no order limitation;

[0131]

[0132]

[0133] in,

[0134] A 1 and A 2 Independently selected from hydrocarbyl C x h 2x+y ; x is an integer from 5 to 35, and y is 1, -1, -3, -5, -7, -9 or -11;

[0135] no 1 , n 2 , L 1 and L 2 The options are as follows:

[0136] no 1 =0,n 2 =0,L 1 and L 2 Linked to form -(CH 2 ) n3 -, n 3 1 to 4. Among them, L 1 and L 2 There are no special restrictions on the type of the two reacting to form -(CH 2 ) n3 - can b...

Embodiment 1～13

[0205] The preparation of embodiment 1~13 compound Y-1

[0206]

Embodiment 1～3

[0208] Add 56g of hexadecanoic acid (0.22mol), 12g of N,N-dimethylamino-1,2-propanediol (0.1mol) into a 500mL reaction flask, add 300mL of dichloromethane, stir well and add 27.8g of N, N'-diisopropylcarbodiimide (DIC) (0.22mol) and 0.2g 4-dimethylaminopyridine (DMAP), after fully stirring and reacting at room temperature for 24h, filtered, and the solid obtained after the filtrate rotary distillation was further recombined Through crystallization and purification, 54 g of the product was obtained with a yield of 96.8%.

[0209] According to the above-mentioned preparation process, the difference is that the 56g hexadecanoic acid in the above-mentioned preparation process is replaced with 62g oleic acid and 61g octadecatrienoic acid (both 0.22mol) respectively. The yield and product structure of the obtained product are shown in Table 1.

[0210] The productive rate and structure of table 1 embodiment 1~3

[0211]

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PUM

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Abstract

The invention provides a liposome, a preparation method thereof, a liposome assembly body and a carrier liposome complex body. The liposome provided by the present invention has the structure of formula (I), the L group is the liposome part on the left and the phosphorylcholine structure on the right, and the two are connected by a specific L group to form a liposome with a specific structure. The liposome of formula (I) provided by the present invention has properties such as long circulation, stimuli responsiveness, and targeting, and has multiple modifiable sites, which can be used to prepare biological agents with various functions, and provide More convenient options.

Description

technical field [0001] The invention relates to the technical field of drug carriers, in particular to a liposome, a preparation method thereof, a liposome assembly and a liposome complex carrying a load. Background technique [0002] At present, liposomes have been widely used as drug carriers. Adriamycin-liposomes, daunorubicin-liposomes, and paclitaxel-liposomes have been on the market for many years. For a long time, liposomes as drug carriers have faced the following four key problems: [0003] (1) Targeted delivery problem: currently clinically used liposomes (represented by DPPC and DSPE liposomes) compound drugs mainly use the EPR effect of the tumor site for passive targeted enrichment. However, this passive targeting is not selective and easily interfered by the complex physiological environment. In addition, depending on the pure EPR effect, the drug concentration in the lesion is often low. In order to achieve effective treatment, it is necessary to increase th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07F9/11C07F9/113C07F9/6518A61K9/127A61K47/34A61P35/00A61K31/704
CPCC07F9/11C07F9/113C07F9/6518A61K9/1271A61K47/34A61P35/00A61K31/704Y02P20/55
Inventor 于喜飞刘三荣王文靓江桑铌李晟冉
Owner 吉林省思睿德生物科技有限责任公司
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