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Docetaxel long-circulating liposome freeze-dried preparation and preparation method thereof

A freeze-dried preparation and docetaxel technology, applied in the field of pharmaceutical preparations, can solve the problems of large average particle size of preparations, side effects of dispersion medium, and undescribed liposome stability, and achieve long circulation time in vivo, high biological efficiency and so on. Availability, the effect of eliminating adverse reactions

Pending Publication Date: 2020-12-22
南京康海磷脂生物技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] CN101322699A and CN101322689A disclose a kind of preparation method of docetaxel liposome and a kind of docetaxel long circulation liposome and freeze-dried powder injection thereof, all used chloroform methanol as solvent in the preparation method, and toxicity is bigger , not easy to remove completely, less safe
[0009] CN101317816A discloses a long-circulation preparation of docetaxel. The solvent of this preparation is chloroform, dichloromethane, dimethyl sulfoxide, etc., which is difficult for industrial production, and the stability of liposomes before and after freeze-drying is not described
[0010] CN101015547A and CN101057831A disclose a new dosage form of docetaxel liposome and its preparation method. The encapsulation efficiency of this preparation is not high (greater than 80%), and the stability of liposome before and after lyophilization is not described
[0011] CN1823732A discloses a kind of docetaxel self-assembled proliposome and its preparation method. This invention needs to add surfactant, which is easy to cause adverse reactions such as allergies, and its dispersion medium will also produce side effects when intravenous injection, and the preparation Larger average particle size (less than 800nm)
[0012] CN101176719A discloses a paclitaxel and docetaxel liposome combination drug and a preparation method thereof. When the preparation is freeze-dried, the organic solution is difficult to freeze-dry, and the organic solvent gas is difficult to handle after drying out
[0013] A variety of antioxidants are added to the prescription, which may cause hormone metabolism disorders, muscle weakness and other symptoms

Method used

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  • Docetaxel long-circulating liposome freeze-dried preparation and preparation method thereof
  • Docetaxel long-circulating liposome freeze-dried preparation and preparation method thereof
  • Docetaxel long-circulating liposome freeze-dried preparation and preparation method thereof

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Effect test

Embodiment 1

[0049] Docetaxel long-circulation liposomal lyophilized formulation prescription

[0050] Docetaxel 3g

[0051] Soy Lecithin (SPC) 60g

[0052] Dipalmitoylphosphatidylglycerol (DPPG) 5g

[0053] Polyethylene glycol phosphatidylglycerol (PG-PEG) 7g

[0054] Mannitol 180g

[0055] Dilute to 1000ml with water for injection

[0056] The preparation process is as follows:

[0057] After docetaxel, soybean phosphatidylglycerol (SPC), dipalmitoylphosphatidylglycerol (DPPG) and polyethylene glycol phosphatidylglycerol (PG-PEG) in the above prescription were completely dissolved in absolute ethanol, vacuum evaporation method The solvent was removed to obtain a liposome membrane. Dissolve mannitol in water for injection as a hydration solution. The hydration temperature is 40±5°C. After the hydration is complete, use a homogenizer and a microporous filter membrane with a suitable pore size to reduce the average particle size to 110±10nm. Aliquot and freeze-dry under bacterial con...

Embodiment 2

[0060] Docetaxel long-circulation liposomal lyophilized formulation prescription

[0061] Docetaxel 4g

[0062] Egg yolk lecithin (EPC) 80g

[0063] Dimyristoylphosphatidylglycerol (DMPG) 6g

[0064] Distearoyl Phosphatidylethanolamine Polyethylene Glycol (DSPE-PEG) 5g

[0065] Glucose 150g

[0066] Dilute to 1000ml with water for injection

[0067] The preparation process is as follows:

[0068] Completely dissolve docetaxel, egg yolk lecithin (EPC), dimyristoylphosphatidylglycerol (DMPG), polyethylene glycol distearoylphosphatidylethanolamine (DSPE-PEG) in the above prescription with absolute ethanol Finally, the solvent was removed by evaporation under reduced pressure to obtain a liposome membrane. Dissolve glucose in water for injection as a hydration solution. The hydration temperature is 50±5°C. After complete hydration, use a homogenizer and a microporous filter membrane with a suitable pore size to reduce the average particle size to 120±10nm. Sterile Subpackag...

Embodiment 3

[0071] Docetaxel long-circulation liposomal lyophilized formulation prescription

[0072] Docetaxel 2g

[0073] Hydrogenated soybean lecithin (HSPC) 70g

[0074] Dimyristoylphosphatidic acid (DMPA) 8g

[0075] Polyethylene glycol phosphatidylethanolamine (PE-PEG) 3g

[0076] Trehalose 170g

[0077] Dilute to 1000ml with water for injection

[0078] The preparation process is as follows:

[0079] After the docetaxel, hydrogenated soybean lecithin (HSPC), dimyristoyl phosphatidic acid (DMPA) and polyethylene glycol phosphatidylethanolamine (PE-PEG) in the above prescription were completely dissolved in absolute ethanol, evaporated under reduced pressure The solvent was removed to obtain liposome membranes. Dissolve trehalose in water for injection as a hydration solution. The hydration temperature is 60±5°C. After the hydration is complete, use a homogenizer and a microporous filter membrane with a suitable pore size to reduce the average particle size to 150±10nm. Aliquo...

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Abstract

The invention relates to a docetaxel long-circulating liposome freeze-dried preparation and a preparation method thereof. The liposome comprises docetaxel, neutral phospholipid, negatively charged phospholipid, long-circulating phospholipid and an excipient. The preparation method comprises steps of preparation, homogenization, sub-packaging, freeze-drying and the like. The liposome is low in toxic and side effects, can prolong retention time of the drug in a body, improve pharmaceutical effect, increase stability of the drug, and is suitable for large-scale production. The preparation does not need to be redissolved in a special solvent, has high encapsulation rate, small particle size and stable properties after redissolution, and is convenient for clinical use.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a fat-soluble anticancer drug docetaxel liposome freeze-dried preparation and a preparation method of the preparation. Background technique [0002] Docetaxel is a taxane compound obtained by semi-synthesis of the precursor compound 10-deacetylbaccatin III extracted from Taxus chinensis. It was first developed by the French Rhone-Planck-Le'an company. Its mechanism of action is similar to paclitaxel, which can accelerate the rate of tubulin assembly into microtubules and prolong the length of microtubules. The overall effect is to enhance tubulin polymerization and inhibit microtubule depolymerization, resulting in the formation of stable non-functional microtubules Bundles, thereby disrupting mitosis and cell proliferation. Its anti-tumor activity is 1.3-12 times that of paclitaxel, and it has no cross-resistance with paclitaxel. Patients with cancer and...

Claims

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Application Information

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IPC IPC(8): A61K9/19A61K9/127A61K31/337A61P35/00
CPCA61K31/337A61K9/19A61K9/127A61P35/00
Inventor 陈文忠张国喜程光秦利利
Owner 南京康海磷脂生物技术有限公司