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Anthracene nucleus medicinal liposome injection and preparation method

A technology of liposomes and anthracyclines, which is applied in drug combinations, pharmaceutical formulations, liquid delivery, etc., can solve problems such as ineffective effects, low concentration of free drugs, and short shelf life, so as to avoid excessively long circulation time and increased Large storage stability, avoid the effect of hand-foot effect

Inactive Publication Date: 2008-06-04
北京天衡药物研究院有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the problem of this technology is that the main phospholipid components used in the current thermosensitive liposome formulations, such as DPPC, have a phase transition temperature of 42°C. In the phase transition temperature range of 39-42°C, the liposome bilayer structure has The colloidal crystalline state is transformed into a liquid crystal state, but the integrity of the liposome is not destroyed. Although the permeability of the phospholipid bilayer structure increases, the actual free drug concentration in the lesion area is not high, and the effect of active drug release is not high. obvious
Because existing technology has deficiency in guaranteeing the stability of anthracycline drug liposome, it is often stored at ultra-low temperature, and the shelf life is short

Method used

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  • Anthracene nucleus medicinal liposome injection and preparation method
  • Anthracene nucleus medicinal liposome injection and preparation method
  • Anthracene nucleus medicinal liposome injection and preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Preparation prescription (50ml capacity)

[0067] Epirubicin Hydrochloride 100mg Citric Acid 365mg

[0068] DPPC 1700mg Sodium Citrate 380mg

[0069] MPPC 100mg Sodium Carbonate 340mg

[0070] DSPG 100mg Lactose 2500mg

[0071] PEG-DSPE 100mg Water for Injection Dilute to 50ml

[0072] Preparation Process:

[0073] Add phospholipids into a round-bottomed flask according to the prescription ratio, add chloroform-methanol (3:1) mixed solvent to dissolve, and remove the solvent by rotary evaporation under reduced pressure at 45°C. The phospholipid forms a film on the inner wall of the round bottom flask, and the prepared film is dried under vacuum for 20 hours to ensure that the organic solvent is completely removed. The citric acid-sodium citrate buffer solution (pH4.0) added to the prepared film, containing 5% lactose, was hydrated at 45-60°C for 1 hour to obtain multilamellar liposomes (MLVs). Under high-pressure conditions at 45°C, pass the prepared MLVs through ...

Embodiment 2

[0075] Preparation prescription (50ml capacity)

[0076] Epirubicin Hydrochloride 100mg Sodium Citrate 380mg

[0077] DPPC 1600mg Sodium Carbonate 340mg

[0078] DSPG 200mg Trehalose 5000mg

[0079] PEG-DSPE 200mg PVP 500mg

[0080] Citric acid 365mg

[0081] Preparation Process:

[0082]Add phospholipids into a round-bottomed flask according to the prescription ratio, add chloroform-methanol (3:1) mixed solvent to dissolve, and remove the solvent by rotary evaporation under reduced pressure at 45°C. The phospholipid forms a film on the inner wall of the round bottom flask, and the prepared film is dried under vacuum for 20 hours to ensure that the organic solvent is completely removed. Add citric acid-sodium citrate buffer (pH4.0) to the prepared film, containing 10% trehalose, and hydrate at 45-60°C for 1 hour to obtain multilamellar liposomes (MLVs). Under high-pressure conditions at 45°C, pass the prepared MLVs through polycarbonate membranes with pore diameters of 2...

Embodiment 3

[0084] Preparation prescription (50ml capacity)

[0085] Epirubicin Hydrochloride 150mg Citric Acid 730mg

[0086] DPPC 1600mg Sodium Citrate 760mg

[0087] MSPC 100mg Sodium Carbonate 680mg

[0088] DSPG 100mg Trehalose 7500mg

[0089] PEG-DSPE 200mg PVP 1000mg

[0090] Preparation Process:

[0091] Add phospholipids into a round-bottomed flask according to the prescription ratio, add a small amount of ethanol to dissolve it, inject it into a preheated buffer solution containing 15% trehalose at 60°C, ultrasonicate for 15 minutes, and dialyze with hydration buffer solution to remove the outer phase Organic solvent, hydration at 60°C for 1 hour to obtain multilamellar liposomes (MLVs), pass the prepared MLVs through polycarbonate membranes with pore diameters of 200nm, 100nm, and 80nm in sequence at a temperature greater than 45°C under high pressure conditions, and obtain particle sizes For large unilamellar liposomes (LUVs) of about 50-250nm, cool the prepared blank lip...

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Abstract

The invention discloses an anthracycline liposome injection, including the injection and a frozen powder injection and a preparation process of the injection. The frozen liposome consists of the anthracycline or an anthracycline hydrochloride, compound neutral phospholipids, surfactant, negative-charge phospholipids, buffers, PH regulators and freezing protection agent. The preparation process includes the following steps: preparation of a hollow liposome, a homogenized liposome, an anthracycline lopsome and an anthracycline lopsome suspension; adding the freezing protection agent; constant volume; sterilization; sub-package; freezing and drying; storage, etc. The liposome injection can be preserved for 12 months under the room temperature with better stability. And the encapsulation rate can be above 95 percent and a granule diameter is between 30 and 300mm. The side effect is low and the technique is simple, thus being convenient for industrial production.

Description

technical field [0001] The invention relates to preparations of anthracyclines and their hydrochlorides, in particular to an injectable thermosensitive liposome of anthracyclines, and also relates to a preparation process of the medicines. [0002] The present invention adopts long-circulation liposome and thermosensitive liposome technology, and in the phospholipid bilayer structure of the liposome that special surfactant (hydrolyzed phospholipid, high molecular polymer etc.) is added, makes liposome The release rate of the drug at the phase transition temperature and above the phase transition temperature increases significantly, because the addition of negatively charged phospholipids in the phospholipid membrane significantly increases the storage stability of the liposome. Background technique [0003] The mechanism of action of anthracycline broad-spectrum antineoplastic drugs and their hydrochloride is mainly: ①By intercalating into DNA double strands, it has high aff...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/19A61K9/10A61K47/24A61K47/26A61K47/34A61K47/36A61K31/704A61P35/00
Inventor 刘全志杨文斌
Owner 北京天衡药物研究院有限公司
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