Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

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
View PDF2 Cites 16 Cited by
  • 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

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

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.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

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

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K9/127A61K31/4745A61K47/24A61K47/48A61K47/34A61P35/04
Inventor 邓意辉李哲
Owner SHENYANG PHARMA UNIVERSITY
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com