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Irinotecan liposome and preparation method thereof

A technology of liposome preparation and Kangzhi, which is applied in the field of medicine

Inactive Publication Date: 2012-06-06
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The residual ethanol requirement in existing doxorubicin liposome (DOXIL, Gloria) products is less than 0.01%, which brings problems

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0008] Example 1 Preparation of blank liposomes

[0009] In order to avoid the influence of the organic solvent in the preparation process, dichloromethane was used to dissolve the lipid, and the blank liposome was prepared by the film dispersion method.

[0010] Blank liposome prescription

[0011] Hydrogenated soybean lecithin (HSPC) 3g

[0012] Cholesterol (CH) 1g

[0013] mPEG 2000 -DSPE 0.75g

[0014] Combine HSPC, CH, mPEG 2000 -DSPE is dissolved in dichloromethane, and the dichloromethane is removed according to the film method to obtain a lipid film. Add ammonium ethylenediaminetetraacetate (NH 4 EDTA) solution, and stirred in a water bath at 65°C for 20 min to obtain the primary blank liposome. Sonicate the primary product probe for 8 min (200 w×2 min, 400 w×6 min), and then pass through 0.8 μm, 0.45 μm, 0.22 μm microporous membranes in turn to obtain a blank liposome suspension.

Embodiment 2

[0015] Example 2 Blank liposome gradient establishment and drug loading

[0016] The methods for gradient establishment include "ion exchange resin method", "dialysis method" and "molecular sieve separation method". The ion-exchange resin method is used as an example to illustrate below.

[0017] Take 0.3 mL of the blank liposome suspension of "Example 1", and load it on a 3 mL anion-cation mixed ion exchange resin column pretreated by centrifugation (wet packing, the volume ratio of anion resin to cation resin is 2: 1 ), centrifuged at 2000 rpm for 4 min to obtain 4 Blank liposome suspension with EDTA transmembrane ion gradient.

[0018] Drug loading: Take 0.1 mL of the above gradient liposomes, add 0.3 mL of CPT-11 solution (3.0 mg / mL), and incubate at 60 °C for 10 min to prepare CPT-11 liposomes.

Embodiment 3

[0019] Example 3 The impact of ethanol on the particle size of blank liposomes

[0020] Measure a certain volume of "Example 1" blank liposome, add 0.0%, 0.1%, 1%, 5.0%, 10.0%, 15%, 20.0%, 25.0% (v / v) ethanol respectively, and mix well After that, the particle size was measured at 0, 4, 8, and 24 h, and the results are shown in Table 1. Adding 5.0% and 10.0% ethanol had no significant effect on liposome particle size within 24 h; however, the particle size increased after adding 20.0% and 25.0% ethanol for 24 h.

[0021] Table 1 Effect of ethanol on the particle size of blank liposomes

[0022] Ethanol concentration (v / v) 0% 0.1% 1% 5% 10% 15% 20% 25% Particle size (0 hour) 85.9 87.3 90.5 88.1 83.7 92.6 99.5 104.0 Particle size (24 hours) 86.1 86.2 89.6 89.6 87.6 97.1 105.2 109.3

[0023] It can be seen from the table that when the ethanol is greater than 15%, the particle size increases.

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PUM

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Abstract

The invention belongs to the technical field of medicine and relates to irinotecan liposome and a preparation method thereof. The method can control ethanol content in liposome during a preparation process and ensure no substantial influence of residual ethanol on liposome property in the preparation process. The invention employs improved ethanol injection method to prepare irinotecan liposome, and a membrane material comprises phospholipid or / and other components. The method comprises steps of: preparing a hydrating medium at 45-75 DEG C and insulating for standby; dissolving lipid phase with ethanol, including absolute ethyl alcohol, in a volume less than 10% of a final volume of a preparation at 45-75 DEG C; adding the hydrating medium into the lipid phase at a certain speed; stirring and dispersing to reduce grain size and obtain a blank liposome; and loading according to a gradient method. The invention can effectively control residual ethanol amount during the preparation process, and physical and chemical properties of the liposome have no significant change.

Description

Technical field: [0001] The invention belongs to the technical field of medicine, and relates to irinotecan liposomes and a preparation method thereof. The liposomes prepared by the method can control the ethanol content in the preparation process, and can ensure that the residual ethanol in the preparation process has no significant effect on the properties of the liposomes. sexual influence. Background technique: [0002] Irinotecan hydrochloride (CPT-11) is a semi-synthetic derivative of camptothecin. It is an effective drug for the treatment of metastatic colorectal cancer, and it is still effective for fluorouracil-resistant cases. The curative effect on leukemia is remarkable, but the existing CPT-11 injection has the disadvantages of short half-life, myelosuppression and gastrointestinal dysfunction. In order to enhance the targeting of drugs, prolong the residence time in the body, enhance the curative effect, and reduce the toxicity, the American PharmaEngine compa...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K31/4745A61K47/24A61K47/48A61K47/34A61P35/04
Inventor 邓意辉李哲
Owner SHENYANG PHARMA UNIVERSITY
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