SN38 lipid composition, and preparation method and application thereof

A technology of lipid composition and phospholipids, which is applied in the direction of drug combination, liposome delivery, drug delivery, etc., can solve the problems of difficult industrialized large-scale production, complex preparation process, and low drug encapsulation efficiency, so as to reduce toxic and side effects, Effects of prolonging circulation time and overcoming multidrug resistance

Active Publication Date: 2018-09-25
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because SN38 has poor affinity with lipids such as phospholipids, it is difficult to stabilize in the membrane, so the liposome preparations disclosed in the above patents all have low

Method used

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  • SN38 lipid composition, and preparation method and application thereof
  • SN38 lipid composition, and preparation method and application thereof
  • SN38 lipid composition, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1 Preparation of SN38 lipid composition freeze-dried powder injection

[0049] Weigh 30mg of SN38, 600mg of soybean lecithin, 60mg of soybean oil, 150mg of cholesterol and 60mg of PEG-DSPE into a 250mL round-bottomed flask, dissolve in 30mL of chloroform:methanol (1:1, v / v), and store at 60-70°C Evaporate under reduced pressure to form a lipid film on the bottle wall, add 30mL of PBS solution (pH=5) containing 10wt% sucrose and 0.1wt% poloxamer 188 to hydrate for 1h to fully hydrate the film, and then homogenize under high pressure (homogeneous Mass pressure 20000psi) 5 times to obtain the lipid composition suspension, which is sub-packed into vials, and freeze-dried to obtain the SN38 lipid composition freeze-dried powder. The freeze-dried SN38 lipid composition freeze-dried powder injection after freeze-drying adds water reconstitution, measures its particle size, electric potential and encapsulation efficiency, its particle size of the result (see figure 1 )...

Embodiment 2

[0050] Example 2 Preparation of SN38 Lipid Composition Freeze-dried Powder

[0051] Weigh 30 mg of SN38, 1200 mg of hydrogenated soybean lecithin, 100 mg of MCT, 200 mg of cholesterol, 50 mg of DSPG, 50 mg of PEG-DSPE, and 50 mg of HS15 in a 100 mL round-bottomed flask, dissolve them in 50 mL of chloroform / methanol (9:1, v / v) mixed solvent, Evaporate under reduced pressure at 60°C to form a lipid film on the bottle wall, add 30mL sodium acetate buffer (pH=3) containing 15wt% sucrose and 0.5wt% PVP-K30 to hydrate for 2 hours, and then homogenize under high pressure to obtain lipid The substance composition suspension is divided into vials and freeze-dried to obtain the product. The freeze-dried phospholipid composition freeze-dried powder was reconstituted with water, and its particle size and encapsulation efficiency were measured. The results showed that the particle size and encapsulation efficiency were 178.2nm and 86.7% respectively.

Embodiment 3

[0052] The preparation of embodiment 3 SN38 lipid composition

[0053] Weigh 30mg of SN38, 335mg of egg yolk lecithin, 10mg of camellia oil, 30mg of TPGS, 50mg of cholesterol and 15mg of PEG-DSPE into a 100mL round bottom flask, and dissolve in 50mL of dichloromethane / methanol (1:1, v / v) mixed solvent Afterwards, spray-dry (inlet temperature: 60°C) to obtain white particles, add 60mL of 10wt% trehalose, 0.5wt% chitosan sodium succinate buffer (pH=4) for hydration for 2 hours, and then homogenize under high pressure A lipid composition suspension is obtained. The particle size and encapsulation efficiency were determined to be 120.8nm and 85.4%, respectively.

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Abstract

The invention relates to a SN38 lipid composition, and a preparation method and application thereof. The SN38 lipid composition comprises SN38, phosphatide, oil for injection, cholesterol, a long-circulating film material, a functional material capable of forming a protection layer on the surface of lipid, and a functional adjuvant capable of reversing drug resistance. The SN38 lipid composition overcomes the problems that drugs are poor in solubility and hard to prepare preparations, that conventional lipid preparations are low in entrapment rate and poor in in-vitro stability, that drugs areprone to rapid leakage and the like in the prior art; and the SN38 lipid composition improves the in-vivo circulation time of drugs, has a certain targeting function, allows drugs to be enriched at tumor sites, reduces toxic and side effect, substantially enhances drug effect, and can overcome the multidrug resistance of tumors to a certain degree.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to an SN38 lipid composition, a preparation method and its use in the preparation of pharmaceutical preparations for treating tumors, especially drug-resistant tumors. Background technique [0002] 7-Ethyl-10-hydroxycamptothecin (SN38) is an active metabolite of irinotecan (CPT-11), a derivative of camptothecin obtained through chemical structure modification. It has the characteristics of strong anti-cancer effect and high anti-cancer activity. In vitro cytotoxicity test shows that for some tumor cell lines, the anti-tumor activity of SN38 is 100-1000 times that of irinotecan. Its mechanism of action is selective inhibition of DNA topoisomerase I (TOPO I). During the action, the camptothecin-like drug lactone ring opens, the acyl group interacts with the nucleophilic part of TOPO I, and forms a camptothecin-like drug-TOPO I- DNA ternary complex, th...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K9/19A61K47/14A61K31/4745A61P35/00
CPCA61K9/0019A61K9/127A61K9/19A61K31/4745A61K47/14A61K47/44
Inventor 李亚平陈伶俐罗肖张丽
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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