Docetaxel freeze-dried microemulsion preparation and preparation method thereof

A technology of docetaxel and emulsion preparations, applied in the directions of freeze-drying delivery, pharmaceutical formulations, emulsion delivery, etc., can solve the problems of small allergic reactions, toxic and side effects, and achieve small allergic reactions, no vascular irritation, and fluidity. Good results

Active Publication Date: 2013-09-18
SHANGHAI MODERN PHARMA ENG INVESTIGATION CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The technical problem to be solved by the present invention is to overcome the allergic reaction and toxic and side effects caused by the use of a large amount of co-solvents in the existing docetaxel injection, and must go through the defects of two-step dilution before use, aiming at the properties of docetaxel To meet the needs of clinical use, a docetaxel freeze-dried microemulsion preparation and a preparation method thereof are provided. The product does not need to go through a cumbersome two-step dilution process before clinical use. Intravenous injection, no vascular irritation, small allergic reaction, hemolysis test shows that it does not produce hemolysis, which provides a new idea for the development of safe and effective docetaxel freeze-dried microemulsion, which is of great significance

Method used

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  • Docetaxel freeze-dried microemulsion preparation and preparation method thereof
  • Docetaxel freeze-dried microemulsion preparation and preparation method thereof
  • Docetaxel freeze-dried microemulsion preparation and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1-16

[0030]The raw material ratio of Examples 1-16 is shown in Table 1 below.

[0031] Table 1

[0032]

[0033]

Embodiment 1

[0035] Preparation of lyophilized microemulsion of docetaxel: 5 mg Solutol HS-15, 20 mg caprylic acid / capric glyceride and 10 mg polyene phosphatidylcholine were heated and dissolved in 11 mg 1,2-propanediol in a water bath at 40 ° C, and the After dissolving, add 0.5 mg of docetaxel; then slowly add 53.5 mg of water for injection (containing 2.5 mg of glucose), stir while adding, filter to obtain a transparent microemulsion with opalescence, lyophilize to remove water, and obtain a lyophilized microemulsion , freeze-dried to remove moisture, and obtained freeze-dried microemulsion.

[0036] Preparation of the docetaxel lyophilized microemulsion dilution: the obtained lyophilized microemulsion was redissolved with 0.9% physiological saline to a docetaxel concentration of 0.7 mg / mL.

[0037] Nicomp380 was used to measure the particle size, and the docetaxel microemulsion prepared in this example was subjected to particle size detection before freeze-drying, and the results were...

Embodiment 2

[0039] Preparation of lyophilized microemulsion of docetaxel: 6 mg of polyoxyethylene castor oil, 25 mg of soybean oil and 6 mg of polyene phosphatidylcholine were heated and dissolved in 14 mg of isopropanol in a 40°C water bath, and after dissolution, docetaxel was added Add 46 mg of 5% glucose injection (containing 2.3 mg of lactose) slowly, stir while adding, and filter to obtain a transparent microemulsion with opalescence, freeze-dry to remove water, obtain a freeze-dried microemulsion, freeze-dry Remove water to obtain freeze-dried microemulsion.

[0040] Preparation of the docetaxel lyophilized microemulsion dilution: the obtained lyophilized microemulsion was redissolved with 0.9% physiological saline to a docetaxel concentration of 0.7 mg / mL. Nicomp380 was used to measure the particle diameter, and the average particle diameter of the diluent was measured to be 41.5nm, and 100% of the particles were below 100nm.

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PUM

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Abstract

The invention discloses a docetaxel freeze-dried microemulsion preparation and a preparation method thereof. The docetaxel freeze-dried microemulsion preparation comprises the following raw materials by weight: 0.05-5 parts of docetaxel, 0.1-40 parts of an oil phase, 5-30 parts of a surfactant, 0-40 parts of a cosurfactant, 5-85 parts of a hydrophilic phase, 0-15 parts of a cosolvent, 0-5 parts of an antioxidant, and 1-40 parts of a freeze-drying protective agent. Specifically, the surfactant is one or several of polyethylene glycol-8-caprylin / caprin, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, poloxamer, polyethylene glycol-12-hydroxystearate, polyethylene glycol stearate 15 and sorbitan monooleate. The preparation method includes: preparing the raw materials into a microemulsion according to the ratio, and then conducting freeze-drying. Before clinical use, the docetaxel freeze-dried microemulsion preparation has no need for a tedious two-step dilution process, after redissolving, the docetaxel freeze-dried microemulsion preparation can be subjected to intravenous injection, and has no vascular irritation and small allergic reaction. Hemolytic experiments show that the docetaxel freeze-dried microemulsion preparation does not generate hemolysis.

Description

technical field [0001] The invention belongs to the field of pharmaceuticals, and in particular relates to a docetaxel freeze-dried microemulsion preparation and a preparation method thereof. Background technique [0002] Docetaxel (also known as docetaxel, docetaxel) is an antineoplastic drug that targets microtubules. Its precursor is extracted from the needles of European yew and obtained by semi-synthesis. It is a cell cycle-specific drug, acting in the M phase, which can promote the abnormal polymerization of microtubules and maintain their stability, thereby inhibiting the formation of spindles and other functions of microtubules during cell mitosis, leading to tumor cell death, and has high antitumor activity . Compared with paclitaxel, it has stronger tubulin affinity and longer intracellular residence time, which is about 2 times that of paclitaxel, so it is more destructive to tumor cells. Docetaxel has good clinical curative effect on breast cancer, prostate can...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K9/19A61K31/337A61K47/24A61K47/26A61K47/32A61K47/34A61K47/36A61K47/44A61P35/00A61K47/10A61K47/14
Inventor 陈志祥杨耀杰陈莉虞丽芳唐姝陆伟根
Owner SHANGHAI MODERN PHARMA ENG INVESTIGATION CENT
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