Irinotecan hydrochloride lipidosome composition and preparation method thereof

A technology of irinotecan hydrochloride and liposome composition is applied in the field of irinotecan hydrochloride liposome composition and preparation thereof, and can solve the problem of irinotecan hydrochloride yield, uncontrollable impurities, high liposome cost, The preparation process is cumbersome and other problems, and the effect of prolonging the residence time in the body, low cost and simple preparation process is achieved.

Active Publication Date: 2016-10-05
HUNAN KELUN PHARM RES CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] CN1980637A patent uses ammonium and polyanion (or substituted ammonium salt) gradient method to prepare irinotecan hydrochloride into liposomes, wherein the polyanion used needs to be purified through a specific process, and the process is cumbersome and expensive
The preparation process is cumbersome, and the yield and impurities of modified irinotecan hydrochloride cannot be controlled
CN102271659B patent has announced a kind of irinotecan hydrochloride liposome, contains irinotecan or irinotecan hydrochloride, neutral phospholipid, cholesterol and distearoyl phosphatidylethanolamine-polyethylene glycol 2000 (mPEG2000-DSPE), cholesterol The weight ratio of irinotecan hydrochloride and mPEG2000-DSPE is 1:3-5, and the weight ratio of irinotecan hydrochloride and mPEG2000-DSPE is 1:0.34~0.38, which is prepared by ion gradient method. Due to the large amount of mPEG2000-DSPE used, resulting High cost of preparing liposomes

Method used

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  • Irinotecan hydrochloride lipidosome composition and preparation method thereof
  • Irinotecan hydrochloride lipidosome composition and preparation method thereof
  • Irinotecan hydrochloride lipidosome composition and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Embodiment 1 The liposome excipient hydrogenated soybean phospholipid (HSPC) of the present invention, the impact of cholesterol weight ratio on irinotecan hydrochloride liposome

[0040] Table 1

[0041]

[0042] Preparation Process:

[0043]Blank liposome preparation: dissolve the hydrogenated soybean lecithin and cholesterol of prescription quantity in table 1 in 65 ℃ of dehydrated alcohols, obtain organic phase, inject it in 50-70 ℃ of ammonium sulfate solution (organic phase and ammonium sulfate solution The volume ratio is 1:5), extruded on the extruder with two 0.1μm extruded films, so that the particle size is 80-120nm. Using pH5.0-7.0 phosphate buffer as the replacement medium, the liposomes are subjected to displacement dialysis using a tangential flow ultrafiltration device (Pellicon tangential flow ultrafiltration system), so that the difference in the ammonium ion gradient of the aqueous phase inside and outside the liposome is greater than 10 3 , to ...

experiment example 2

[0052] Experimental example 2 The influence of liposome drug lipid ratio of the present invention on irinotecan hydrochloride liposome

[0053] The prescription of Table 3 is prepared irinotecan hydrochloride liposome according to the same preparation method of embodiment 1. The indexes of the prepared liposomes are shown in Table 4.

[0054] table 3

[0055]

[0056] Table 4

[0057]

[0058] From the above experimental results, it can be seen that when the drug-lipid ratio was 1:4.5, the encapsulation efficiency of irinotecan hydrochloride liposome reached more than 99%, and the phospholipid ratio in the prescription was reduced. When the drug-lipid ratio was 1:4, the encapsulation efficiency was only 1:4. 91.05%. When the drug-to-lipid ratio is 1:6, although the encapsulation efficiency also reaches 99.20%, the amount of phospholipid used is large and the cost is high. Therefore, the preferred drug-to-lipid ratio is 1:4.5.

Embodiment 3

[0059] Example 3 The influence of the preparation process of the present invention on the hemolytic phosphatidylcholine in irinotecan hydrochloride liposomes

[0060] table 5

[0061]

[0062] preparation

[0063] Sample a: According to the prescription in Table 5, the preparation process was the same as in Example 1 to obtain sample a.

[0064] Sample b: Preparation of blank liposomes: Dissolve hydrogenated soybean lecithin and cholesterol in absolute ethanol to obtain an organic phase, which is injected into the ammonium sulfate solution of the above prescription to obtain blank liposome colostrum, which is homogenized by high pressure The machine performs high-pressure homogenization on the colostrum, 500Bar homogenization for 3 times, 1000Bar homogenization for 3 times, and then use 2 pieces of 0.1μm extrusion film to extrude on the extruder to make the particle size 80-120nm. Using pH 5.0-7.0 phosphate buffer as the replacement medium, the tangential flow ultrafiltra...

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Abstract

The invention provides an irinotecan hydrochloride lipidosome composition, which consists of the following ingredients in parts by weight: 1 part of irinotecan hydrochloride, 2-6 parts of hydrogenated soybean phosphatide, 1.0-2.25 -parts of cholesterol and 0.04-0.20 parts of distearoyl phosphoethanolamine-polyethylene glycol 2000. The invention also provides a preparation method of the lipidosome composition. The lipidosome disclosed by the invention significantly reduces cost, and the lipidosome is good in stability,low in content of impurities, high in safety and easy for industrial mass production.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations. More specifically, the present invention relates to a liposome composition of irinotecan hydrochloride and a preparation method thereof. Background technique [0002] With the aging of the global population and the improvement of material living standards, the prevalence and mortality of colorectal cancer are gradually increasing in my country and even in the world, and it is one of the ten common malignant tumors. There are about one million new cases worldwide each year, and at least half a million patients die at the same time. In general, economically developed countries have a higher incidence. Colorectal cancer has a high incidence rate in developed countries such as the United States and Japan, and is the second leading cause of death among cancer patients. In my country, colorectal cancer, like lung cancer, has been on the rise in recent years, and currently accounts for the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K31/4745A61K47/34A61P35/00
Inventor 苏正兴赵栋张瑞霞陈际园王利春王晶翼
Owner HUNAN KELUN PHARM RES CO LTD
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