Preparation of docetaxel long-circulating liposome and freeze-dried powder injection thereof

A long-circulating liposome and docetaxel technology, which is applied to freeze-dried powder injection and its preparation, contains insoluble anticancer drug docetaxel long-circulating liposome field, can solve the problem of hindering liposome, stable It can improve the drug loading and stability, reduce unsafe factors, and have excellent storage stability.

A long-circulating liposome and docetaxel technology, which is applied to freeze-dried powder injection and its preparation, contains insoluble anticancer drug docetaxel long-circulating liposome field, can solve the problem of hindering liposome, stable It can improve the drug loading and stability, reduce unsafe factors, and have excellent storage stability.

CN101322689AActive Publication Date: 2008-12-17HAINAN SIMCERE PHARMA CO LTD
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  • Preparation of docetaxel long-circulating liposome and freeze-dried powder injection thereof
  • Preparation of docetaxel long-circulating liposome and freeze-dried powder injection thereof
  • Preparation of docetaxel long-circulating liposome and freeze-dried powder injection thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0054] Preparation prescription (100mL capacity)

[0055] Docetaxel 100mg

[0056] Soy Phospholipids (SPC) 1.5g

[0057] Distearoylphosphatidylglycerol (DSPG) 150mg

[0058] Cholesterol 600mg

[0059] a-Tocopherol 17mg

[0060] Sucrose about 10g

[0061] Sodium citrate about 294mg

[0062] Citric acid amount

[0063] Water for injection to the required volume

[0064] The preparation process is as follows:

[0065] Select soybean lecithin, distearoylphosphatidylglycerol, cholesterol and a-tocopherol in chloroform solution and mix uniformly according to the formula; use spray drying method to remove chloroform under reduced pressure to form lipid mixture; prepare 0.01M sodium citrate solution , Dissolving sucrose in sodium citrate solution as a hydration solution, the hydration temperature is generally between 55°C±5°C, multi-lamellar liposome suspension; after hydration is complete, use a high-pressure homogenizer to homogenize to an average The particle size is 100±1...

Embodiment 2

[0067] Preparation prescription (100mL capacity)

[0068] Docetaxel 200mg

[0069] Egg Yolk Lecithin (EPC) 4g

[0070] Dimyristoylphosphatidylglycerol (DMPG) 1g

[0071] Cholesterol 1g

[0072] a-tocopheryl succinate 90mg

[0073] Lactose about 10g

[0074] Sodium succinate about 800mg

[0075] Succinic acid amount

[0076] Water for injection to the required volume

[0077] The preparation process is as follows:

[0078] Select egg yolk lecithin, dimyristoyl phosphatidylglycerol, cholesterol and a-tocopheryl succinate to dissolve in chloroform-methanol (2:1) solution and mix well according to the formula; remove the organic solvent under reduced pressure by evaporation under reduced pressure , to form a lipid mixture; prepare 0.03M sodium succinate solution, dissolve lactose in sodium succinate solution as a hydration solution, the hydration temperature is generally 65 ° C ± 5 ° C, multi-lamellar liposome suspension; After the hydration is complete, use a high-pressu...

Embodiment 3

[0080] Preparation prescription (100mL capacity)

[0081] Docetaxel 400mg

[0082] Distearoylphosphatidylcholine (DSPC) 12g

[0083] Distearoylphosphatidylglycerol (DMPG) 2.4g

[0084] Cholesterol 6g

[0085] a-Tocopherol 100mg

[0086] Trehalose about 20mg

[0087] Phosphate about 1.5g

[0088] Water for injection to the required volume

[0089] The preparation process is as follows:

[0090] Select distearoylphosphatidylcholine, distearoylphosphatidylglycerol, cholesterol and a-tocopherol according to the formula and dissolve them in chloroform-methanol (2:1) and mix them uniformly; quality mixture; prepare 0.05M phosphate buffer solution, dissolve trehalose in phosphate solution as a hydration solution, the hydration temperature is generally 45°C±5°C, multi-lamellar liposome suspension; after complete hydration Use a high-pressure homogenizer to homogenize to an average particle size of 80 ± 10nm, dilute to the volume with water for injection and adjust to a concent...

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Abstract

The invention discloses a preparation technique of non-pegylation docetaxel long-circulating liposome which meets clinical and large-scale production requirements and a freeze-dried powder-injection; the liposome consists of docetaxel, neutral phospholipid, charged phospholipid, cholesterin, antioxidant, excipient, buffering agent and water for injection; the preparation technique includes the following steps: preparing multivesicular liposome, homogenizing the liposome, fixing volume, sterilizing, split charging, freeze drying, etc. The liposome increases the solubility of drugs, overcomes poor stability of docetaxel injection and toxicity caused by complex solvent and prolongs the in vivo circulating time of drugs; compared with pegylation long-circulating liposome, the toxicity is decreased and the inhibiting effect on tumor cells is strengthened.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a long-circulating liposome containing an insoluble anticancer drug docetaxel, a freeze-dried powder injection and a preparation method thereof. Background technique [0002] Docetaxel is a taxane anticancer drug that is semi-synthesized from the precursor extracted from the needles of yew berry. Its anti-cancer mechanism is to stimulate the polymerization of cathelicidin, promote the assembly of microtubule dimers into microtubules, and cause cell proliferation to stop at the stage of mitotic quiescence (G2 / M). FDA approved docetaxel for the treatment of breast cancer, ovarian cancer, non-small cell lung cancer and pancreatic cancer, and has certain effects on primary and metastatic cancers such as head and neck squamous cell carcinoma and malignant melanoma. Due to its anti-cancer mechanism and exact curative effect, it has become one of the most valuable anti-cancer d...

Claims

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Application Information

Patent Timeline
17 Dec 2008
Publication
CN101322689A
IPC
A61K9/127; A61K9/10; A61K31/337; A61K47/24; A61P35/00
Inventors
林巧平; 王青松