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ABT-199 nano-emulsion dispersing agent and preparation method thereof

A technology of ABT-199 and ABT-1994%, applied in the preparation of ABT-199 nano-emulsion dispersant, in the field of ABT-199 nano-emulsion dispersant, it can solve the problem of poor water solubility, low bioavailability, strong toxic and side effects of compounds, etc. problems, to achieve the effects of good stability, simple preparation method, high encapsulation rate and drug loading capacity

Inactive Publication Date: 2018-05-18
XIAN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of this invention is to provide a kind of ABT-199 nanoemulsion dispersant, which solves the problems of poor water solubility, low bioavailability and strong toxic and side effects of the compound

Method used

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  • ABT-199 nano-emulsion dispersing agent and preparation method thereof
  • ABT-199 nano-emulsion dispersing agent and preparation method thereof
  • ABT-199 nano-emulsion dispersing agent and preparation method thereof

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preparation example Construction

[0035] A preparation method of ABT-199 nanoemulsion dispersant, such as figure 1 As shown, the specific steps are as follows:

[0036] Step 1. Weigh raw materials: weigh 4% to 8% of ABT-199, 28% to 40% of wrapping material, 20% to 34% of surfactant, and 29% to 38% of lyoprotectant according to mass percentage;

[0037] Step 2. Dissolve ABT-199 in ethanol, the volume ratio of ABT-199 and ethanol is 1:20, then mix the wrapping material and surfactant together into the ethanol solution, after fully dissolved, filter to remove impurities, filter Use a fat-soluble filter membrane with a pore size of 0.22 μm to obtain a mixed solution;

[0038] Step 3. Slowly add the mixed solution obtained in step 2 into deionized water at a rate of 10-20ml / min. The volume ratio of the mixed solution to deionized water is 1:10. Stir at a rate of 300-500rpm , followed by ultrasonic treatment, the ultrasonic treatment uses a probe-type ultrasonic breaker, the power is 400-800W, the ultrasonic treat...

Embodiment 1

[0043] A preparation method of ABT-199 nanoemulsion dispersant, specifically implemented according to the following steps:

[0044] Step 1. Weigh raw materials: weigh 4% of ABT-199, 32% of wrapping material, 28% of surfactant, and 36% of lyoprotectant by mass percentage;

[0045] Step 2. Dissolve 4g of ABT-199 in 80ml of ethanol. Use soybean lecithin as the wrapping material and Tween-80 as the surfactant. Mix 32g of soybean lecithin and 28g of Tween 80 into the ethanol solution. After fully dissolving, Impurities are removed by filtration, and the filtration is carried out with a fat-soluble filter membrane with a pore size of 0.22 μm to obtain a mixed solution;

[0046] Step 3. Slowly add the mixed solution obtained in step 2 into 800 deionized water, control the adding speed to 10ml / min, stir, and the stirring speed is 300rpm, and then carry out ultrasonic treatment. The ultrasonic treatment utilizes a probe type ultrasonic breaker with a power of 400W, each cycle of ultra...

Embodiment 2

[0052] A preparation method of ABT-199 nanoemulsion dispersant, specifically implemented according to the following steps:

[0053] Step 1. Weigh raw materials: weigh 5% of ABT-199, 30% of wrapping material, 29% of surfactant, and 36% of lyoprotectant by mass percentage;

[0054] Step 2. Dissolve 5g of ABT-199 in 100ml of ethanol, use lecithin as the wrapping material, and use poloxamer 188 as the surfactant, mix 30g of lecithin and 29g of poloxamer 188 into the ethanol solution, wait until fully After dissolving, filter to remove impurities, and filter using a fat-soluble filter membrane with a pore size of 0.22 μm to obtain a mixed solution;

[0055] Step 3. Slowly add the mixed solution obtained in step 2 into 1000 deionized water, control the adding speed to 12ml / min, stir at a stirring speed of 400rpm, and then perform ultrasonic treatment. The ultrasonic treatment utilizes a probe type ultrasonic breaker with a power of 600W, each cycle of ultrasonic treatment time is 7...

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Abstract

The invention discloses an ABT-199 nano-emulsion dispersing agent which comprises, in total weight percent of 100%, 4%-8% of ABT-199, 28%-40% of wrapping materials, 20%-34% of surfactants and 29%-38%of cryoprotectants. The wrapping materials are one or mixture of soybean phospholipid, lecithin and cholesterol, the surfactants are nonionic surfactants and include one or mixture of Tween 80, poloxamer 188, PEG-PLGA (polyethylene glycol-polylactic acid), and the cryoprotectants are one or mixture of mannitol and glucose. The invention further discloses a preparation method of the ABT-199 nano-emulsion dispersing agent. The problems of poor water solubility, low bioavailability and strong in-vivo toxic and side effects of a compound in the prior art are solved.

Description

technical field [0001] The invention belongs to the field of nano-biotechnology, and specifically relates to an ABT-199 nano-emulsion dispersant, and also relates to a preparation method of the ABT-199 nano-emulsion dispersant. Background technique [0002] Bcl-2 (B-cell lymphoma-2) protein has the effect of inhibiting cell apoptosis, which has an important relationship with the occurrence and development of tumors, and many studies have proved its mechanism of action. In terms of treatment, Bcl-2 protein is also a very popular target for tumor suppression, and many targeted lead drug compounds have been developed. Among them, ABT-199 is a Bcl-2 inhibitor developed by AbbVie. It has entered the clinical trial stage. Its phase I trial enrolled 84 patients with relapsed / refractory CLL / SLL and 44 patients with relapsed / refractory CLL. In patients with non-Hodgkin's lymphoma, after ABT-199 treatment, the response rate of CLL / SLL was 79%, of which the complete response rate was ...

Claims

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Application Information

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IPC IPC(8): A61K9/19A61K9/107A61K47/26A61K47/24A61K31/635A61P35/00
Inventor 张瑞三李科成凡邵玲巧徐仓宝汪洋
Owner XIAN MEDICAL UNIV
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