Docetaxel liposome sterile lyophilized preparation and preparation method thereof

A freeze-dried preparation, the technology of docetaxel, which is applied to the liposome sterile freeze-dried preparation of the fat-soluble drug docetaxel and its preparation field, can solve the problem of drug leakage, inability to reconstitute liposomes, and preparation stability. investigation and other issues to achieve the effect of easy access, low price and favorable stability

Inactive Publication Date: 2011-06-08
QILU PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it did not investigate the stability of the liposome preparation after freeze-drying and reconstitution, especially the encapsulation efficiency and particle size of the drug after reconstitution.
In addition, the present invention has used sucrose, glucose and mannitol as the freeze-drying protection agent according to the disclosed method, but the freeze-dried product with better appearance cannot be obtained, and the liposome cannot be reconstituted after reconstitution, and the drug leakage is serious
[0017] CN101015547A discloses a new dosage form of docetaxel liposome and its preparation method, but its sterilization method adopts high-pressure sterilization at 121 degrees Celsius, which will undoub

Method used

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  • Docetaxel liposome sterile lyophilized preparation and preparation method thereof
  • Docetaxel liposome sterile lyophilized preparation and preparation method thereof
  • Docetaxel liposome sterile lyophilized preparation and preparation method thereof

Examples

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Effect test

Embodiment 1

[0063] The preparation of embodiment 1 docetaxel long circulation liposome

[0064] Weigh 6 grams of soybean lecithin, mPEG 2000 - Dissolve 1 g of DSPE and 0.15 g of cholesterol in 10 ml of tert-butanol, stir and dissolve at 55°C to obtain a phospholipid solution. Weigh 0.2 g of docetaxel and dissolve it in the phospholipid solution. Prepare a phosphate buffer solution with a concentration of 10 mM, adjust the pH to 4.5, add 4 grams of mannitol and 8 grams of maltose, and fully stir to dissolve. Measure 100ml of buffer solution into the phospholipid solution, and incubate with stirring at 50°C for 30 minutes to obtain a coarse suspension of liposomes. The crude suspension was added to the microfluidizer, and the 5000psi was circulated 5 times, and the 15000psi was circulated 8 times. The docetaxel long-circulating liposomes are obtained after being filtered through 0.8um, 0.45um and 0.22um filter membranes respectively.

[0065] After determination, the average particle si...

Embodiment 2

[0067] The preparation of embodiment 2 common docetaxel liposomes

[0068] Weigh 5 g of soybean lecithin and 0.1 g of cholesterol and dissolve in 10 ml of ethanol, stir and dissolve at 55° C. to obtain a phospholipid solution. Weigh 0.3 g of docetaxel and dissolve it in the phospholipid solution. Prepare a phosphate buffer solution with a concentration of 10 mM, adjust the pH to 4.5, add 3 grams of mannitol and 6 grams of maltose, and fully stir to dissolve. Measure 100ml of buffer solution into the phospholipid solution, and incubate with stirring at 50°C for 30 minutes to obtain a coarse suspension of liposomes. This crude suspension was added to the microfluidizer, 5000psi was circulated 3 times, and 15000psi was circulated 5 times. The docetaxel liposomes were obtained after being filtered through 0.8um, 0.45um and 0.22um filter membranes respectively.

[0069] After determination, the average particle size of the liposome obtained according to the above steps is 80nm, ...

Embodiment 3

[0071] The preparation of embodiment 3 docetaxel liposomes without cholesterol

[0072] Weigh 60 grams of soybean lecithin and dissolve it in 100 ml of tert-butanol, stir and dissolve at 55° C. to obtain a phospholipid solution. Weigh 1.5 g of docetaxel and dissolve it in the phospholipid solution. Prepare a phosphate buffer solution with a concentration of 10 mM, adjust the pH to 4.5, add 50 grams of mannitol and 100 grams of maltose, and fully stir to dissolve. Measure 1000ml of buffer solution into the phospholipid solution, and incubate with stirring at 50°C for 30 minutes to obtain a coarse suspension of liposomes. The crude suspension was added to the microfluidizer, and the 5000psi was circulated 5 times, and the 15000psi was circulated 8 times. The docetaxel liposomes were obtained after being filtered through 0.8um, 0.45um and 0.22um filter membranes respectively.

[0073] After determination, the average particle size of the liposome obtained according to the abov...

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Abstract

The invention relates to a docetaxel liposome sterile lyophilized preparation and preparation method thereof, and the docetaxel liposome sterile lyophilized preparation comprises docetaxel, natural lecithin, PEG-DSPE, cholesterol, a protective agent for lyophilization, and buffer salts. The natural lecithin, PEG-DSPE, cholesterol, and docetaxel are dissolved in a organic solvent; a buffer solution containing the protective agent for lyophilization is added into mixed solution; the solution is incubated for 10-60 min for decreasing the average particle size of the liposome to 50-200 nm; and the preparation is obtained after bacilli-eliminated filtration and lyophilization. The docetaxel liposome prepared by the invention has the advantages of less toxic and side effect and higher curative effect when compared with commercially available ordinary injections at present. The preparation method of the invention is simple and practical, and is applicable to industrial production; and the prepared docetaxel liposome has high encapsulation efficiency and good stability.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a liposome sterile freeze-dried preparation of fat-soluble drug docetaxel and a preparation method thereof. Background technique [0002] Docetaxel (also known as docetaxel) injection, which was successfully developed by the French company Rhone-Planck-Anle in 1986, is another new type of anti-microtubule drug after paclitaxel. It was first launched in Mexico in April 1995. It was subsequently listed in Britain, the United States, France, Italy, Germany, Japan and other countries. [0003] Compared with paclitaxel, docetaxel has less efflux in and out of cells and has a significant effect of inducing apoptosis at low dose. Many in vitro and clinical studies have confirmed that docetaxel has a radiosensitizing effect on a variety of tumor cells and does not aggravate the radiation damage of normal tissues. The affinity of docetaxel is twice that of paclitax...

Claims

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Application Information

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IPC IPC(8): A61K9/19A61K31/337A61K47/34A61P35/00A61K47/24
Inventor 李伯涛王晶翼杨清敏王栋海张明会杨光丽王琳琳
Owner QILU PHARMA
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