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Process for preparing Paclitaxel liposome preparation

A technology of liposome preparations and paclitaxel, which is applied in the preparation of paclitaxel liposome preparations and the preparation of targeted preparations, can solve the problems of fusion, tolerance improvement, toxicity reduction, etc., and achieve slow clearance and long residence time Prolonged, reduced affinity effects

Inactive Publication Date: 2007-08-08
XIAN LIBANG PHARMA TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Paclitaxel is a broad-spectrum anti-tumor drug derived from the bark of the yew plant or chemically synthesized. It is currently used to treat ovarian cancer, breast cancer and non-small cell lung cancer. Because paclitaxel is insoluble in water and many pharmaceutical solvents, Therefore, the formulations currently on the market use absolute ethanol and polyoxyethylene castor oil as solubilizing carriers. The latter can cause the release of histamine and cause severe allergic reactions. Therefore, the use of this drug is limited.
[0003] Liposome (liposome) is a new type of drug delivery system. Current experiments show that paclitaxel liposome formulations have similar curative effects compared with injections, but have reduced toxicity and improved tolerance.
The particle size of traditional liposomes is relatively large (the average particle size is above 1 μm), and the encapsulation efficiency and stability are relatively poor. Due to the large particle size, it is easy to produce fusion and leakage, which significantly reduces the stability of the drug. Since the large particle size liposomes are easily swallowed by the phagocytes of the reticuloendothelial system (RES), they are cleared out of the blood circulation system, thus reducing the concentration of the drug in the tumor tissue, thereby reducing the clinical efficacy

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] (1) Prescription

[0023] Phosphatidylcholine Cholesterol Myristate Paclitaxel HSPE-PEG 2000 Distearoylphosphatidylcholine

[0024] Mass 355mg 59.1mg 8mg 6mg 74.4mg 16.2mg

[0025] Number of moles (mmol) 46.71052632 15.3109 3.50877 0.70264 2.693700217 0.02023482

[0026] Mole percent 67.78463321 22.2186 5.0918 1.01965 3.909000724 0.02936405

[0027] Lyoprotectant 10% sucrose

[0028] Hydration buffer Phosphate buffer pH=6.8

[0029] Antioxidant vitamin E metal ion complexing agent EDTA-2Na

[0030] (2) Preparation of proliposomes

[0031] Egg yolk lecithin, cholesterol, myristic acid, paclitaxel, HSPE-PEG in the prescribed amount 2000 and distearoylphosphatidylcholine in a test tube, and add chloroform-methanol (9:1~1:1), under the protection of nitrogen, heat in a water bath at 20~60°C, oscillate to make the solution clear and transparent, and remove it with nitrogen After the solvent is removed, vacuumize for 4 hours to obtain a lipid film.

[0...

Embodiment 2

[0037] (1) Prescription

[0038] Phosphatidylcholine Cholesterol Myristate Paclitaxel HSPE-PEG 2000 Distearoylphosphatidylcholine

[0039] Mass 3550mg 591mg 80mg 60mg 744mg 162mg

[0040] Number of moles (mmol) 46.71052632 15.3109 3.50877 0.70264 2.693700217 0.02023482

[0041] Mole percent 67.78463321 22.2186 5.0918 1.01965 3.909000724 0.02936405

[0042] Lyoprotectant 10% sucrose

[0043] Hydration buffer Phosphate buffer pH=6.8

[0044] Antioxidant vitamin E metal ion complexing agent EDTA-2Na

[0045] (2) Preparation of proliposomes

[0046] Egg yolk lecithin, cholesterol, myristic acid, paclitaxel, HSPE-PEG in the prescribed amount 2000 and distearoylphosphatidylcholine in a round-bottomed flask, and add an appropriate amount of chloroform-methanol (9:1~1:1) mixed solvent, under the protection of nitrogen, heat in a water bath at 20~60°C, and oscillate to make the solution clear and transparent , and then put it on a rotary evaporator to remove the sol...

Embodiment 3

[0054] (1) Prescription

[0055] Phosphatidylcholine Cholesterol Myristate Paclitaxel HSPE-G 200 Distearoylphosphatidylcholine

[0056] Mass 35.50g 5.91g 0.8g 0.6g 7.44g 1.62g

[0057] Number of moles (mmol) 46.71052632 15.3109 3.50877 0.70264 2.693700217 0.02023482

[0058] Mole percent 67.78463321 22.2186 5.0918 1.01965 3.909000724 0.02936405

[0059] Lyoprotectant 10% sucrose

[0060] Hydration buffer Phosphate buffer pH=6.8

[0061] Antioxidant vitamin E metal ion complexing agent EDTA-2Na

[0062] (2) Preparation of proliposomes

[0063] Egg yolk lecithin, cholesterol, myristic acid, paclitaxel, HSPE-PEG in the prescribed amount 2000 and distearoylphosphatidylcholine in a beaker, and add an appropriate amount of chloroform-methanol (9:1 ~ 1:1), under the protection of nitrogen, heat in a water bath at 40°C, stir to make the solution clear and transparent, and then use a micro-spray The drier (miniature spray drying equipment) removes the solvent,...

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Abstract

The invention relates to a method for preparing drug rehabilitation liposome agent, which comprises that using film disperse method or atomizing drying method to prepare long-circulation rehabilitation liposome, using cholesterol, distearin acyl phosphatidyl choline and myristate as stabilizers, using sucrose as freezing preservative, using chloroform and chloroform as organic solvents; and using amphipathic carbowax derivative to decorate the liposome membrane; and using compression or high-pressure homogeneity method to make the diameter of liposome smaller than 100nm and the package rate higher than 85%. The invention has less toxicity and high stability, as one novel drug slow-release target agent.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, and relates to a preparation method of a targeted preparation, in particular to a preparation method of a paclitaxel liposome preparation. Background technique [0002] Paclitaxel is a broad-spectrum anti-tumor drug derived from the bark of the yew plant or chemically synthesized. It is currently used to treat ovarian cancer, breast cancer and non-small cell lung cancer. Because paclitaxel is insoluble in water and many pharmaceutical solvents, Therefore, in the currently marketed formulations, absolute ethanol and polyoxyethylene castor oil are used as solubilizing carriers, and the latter can cause the release of histamine, leading to severe allergic reactions. Therefore, the use of the drug is limited. [0003] Liposome (liposome) is a new type of drug delivery system. Current experiments show that paclitaxel liposome preparation has similar curative effect compared with injection...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K31/337A61K47/34A61P35/00A61K47/24A61K47/28
Inventor 佐建锋傅经国王九成杨洁党晓怡
Owner XIAN LIBANG PHARMA TECH
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