Dual-medicine total-conveying system and making method and application thereof

A co-delivery and dual-drug technology, applied in the field of biomedicine, can solve the problems of complex preparation process and high risk of side effects, and achieve the effect of simple preparation process, excellent effect and inhibition of tumor growth

Active Publication Date: 2019-05-14
THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the preparation process of the above-mentioned liposome co-delivery system is complicated, not only needs to use a variety of lipid materials, but also needs to be prepared in a copper gluconate / triethylamine buffer system, so that cytarabine and daunorubicin can be combined with The copper ions in the solution form a complex according to a certain molar ratio to ensure the residence time of the drug in the liposome, which involves the use of organic solvents and has the problem of high risk of toxic and side effects

Method used

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  • Dual-medicine total-conveying system and making method and application thereof
  • Dual-medicine total-conveying system and making method and application thereof
  • Dual-medicine total-conveying system and making method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1: Preparation of homoharringtonine-loaded micelles

[0049] (1) Dissolve 15.0-100.0 mg of block copolymer and 5.0 mg of homoharringtonine in 4 mL of phosphate buffer, and stir to obtain polymer suspension A; the block copolymer is selected from polyethylene caprolactam-polyacetic acid Vinyl ester-polyethylene glycol (Soluplus), methoxy polyethylene glycol (mPEG)-polycaprolactone (PCL) (mPEG-PCL, molecular weight: 4000D), distearoylphosphatidylethanolamine (DSPE)- Polyethylene glycol 2000 (PEG 2000 )(DSPE-PEG 2000 , Molecular weight: 2807D), polyoxyethylene polyoxypropylene ether block copolymer (purchased from BASF, Germany, molecular weight 9840D-14600D, the content ratio of polyoxyethylene and polyoxypropylene is 80:20), polylactic acid-glycolic acid One or more of the copolymers (PLGA, 10KD-40KD, the content ratio of polylactic acid and glycolic acid is 50:50), preferably Soluplus (commercially available from BASF, Germany, molecular weight 120KD, polyethylene ...

Embodiment 2

[0057] Example 2: Load doxorubicin

[0058] (1) Dissolve 50.0-200.0 mg of the block polymer in 3 mL of phosphate buffer, stir until completely dissolved, and obtain a clear solution D;

[0059] (2) Dissolve adriamycin hydrochloride in water to prepare an aqueous solution of adriamycin hydrochloride with a concentration of 3-8 mg / mL;

[0060] (3) Mix the clear solution D with the homoharringtonine-loaded micelle C obtained in Example 1, and add 1 mL of the doxorubicin salt obtained in step (2) dropwise under heating at 25-70°C and stirring at 100-1000 r / min Stir the aqueous acid salt solution for 20-120 min to obtain solution E; the polymer of homoharringtonine micelle C is the same as the polymer used in step (1);

[0061] (4) The solution E was allowed to stand at room temperature, and filtered with a 0.22μm polyethersulfone water-based filter membrane to remove the free drug that was not encapsulated into the micelles to obtain micelle F that simultaneously contained homoharringtoni...

Embodiment 1

[0065] The average hydration diameter of micelle F of Example 1 is 80nm (such as figure 1 Shown), the drug loading of doxorubicin is 5%, and the encapsulation efficiency is 75%; the performance parameters of other embodiments are shown in Table 2 and Table 3.

[0066] Table 3 Dual-drug co-delivery system with different ratios of DOX and HHT

[0067]

[0068] Experiment 1: Inhibition of single free drug, combination of two free drugs and dual drug co-delivery system on the proliferation of various hematological tumors and solid tumor cells in vitro

[0069] Taking HL60 / A cells (HL60 cells resistant to adriamycin) as an example, the specific implementation methods are as follows:

[0070] In Corning 96-well U-shaped plate, use 100μL RPMI-1640 medium (containing 10% fetal bovine serum and 1% penicillin) to culture 5×10 per well 4 Cells. The experimental group included: 1) Single HHT group (H): HHT was dissolved in dimethyl sulfoxide (DMSO) to obtain 10 mg / mL mother liquor; 2) Single DOX ...

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Abstract

The invention discloses a dual-medicine total-conveying system and a making method and application thereof. The system is prepared from raw materials including a block copolymer, homoharringtonine anddoxorubicin hydrochloride. The dual-medicine total-conveying system has a higher killing effect on various blood tumors and solid tumor cells and particularly can be applied to medicine for treatingrecurrent and refractory AML1-ETO acute myeloid leukemia, and the effect is excellent; the feasible medicine conveying system can be provided for tumor growth inhibition and leukemia treatment, and the prospect is wide. In the making process of the dual-medicine total-conveying system, any organic solvent is not needed, and the preparation technology is simple; the system has a higher anti-tumor function, the toxic and side effect can be lowered, and the demands of industrial production and clinical medicine application are met.

Description

Technical field [0001] The present invention relates to the technical field of biomedicine, in particular to a dual-drug co-delivery system, its preparation method and its application in preparing anti-tumor drugs. Background technique [0002] Chemotherapy is a treatment that uses chemical drugs to prevent the proliferation, infiltration, and metastasis of cancer cells, and ultimately kills cancer cells. It is the main treatment for most solid tumors and hematological tumors. The chemical drugs used during chemotherapy are called chemotherapy drugs. Due to the emergence of chemotherapeutic drug resistance and dose-dependent side effects, a single drug can no longer meet the clinical needs, so a combination of multiple chemotherapeutic drugs is used to solve this problem. Although the combined use of multiple chemotherapeutic drugs can reduce the toxic side effects and the possibility of drug resistance caused by a single drug, there are problems such as the number of administra...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K31/55A61K31/704A61K47/10A61K47/24A61K47/32A61K47/34A61P35/00A61P35/02
CPCA61K47/10A61K47/32A61K47/24A61K47/34A61P35/00A61K31/704A61K31/55A61P35/02A61K9/1075A61K9/08
Inventor 许海燕闫豆豆孟洁刘健温涛葛洋洋
Owner THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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