Dasatinib liposome preparation and preparation method thereof

A technology of dasatinib and nilipid, which is applied in the field of nano-drug delivery, can solve the problems of high frequency of medication, large effective dose, and limited bioavailability, and achieve improved encapsulation efficiency, good biocompatibility, The effect of improving bioavailability

Active Publication Date: 2021-02-12
SHANGHAI JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

As an oral tablet, its effective dose is large and the frequency of medication is high, and its bioavailability is limited. There are relevant literatures showing that its clinical treatment AUC 0-t The value is 409.2ng*h / mL, A max 122.5ng / mL

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  • Dasatinib liposome preparation and preparation method thereof
  • Dasatinib liposome preparation and preparation method thereof
  • Dasatinib liposome preparation and preparation method thereof

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preparation example Construction

[0072] The preparation method of Dasatinib liposome preparation

[0073] The preparation method of dasatinib liposome preparation of the present invention, comprises the steps:

[0074] (1) prepare the blank liposome that inner water phase and outer water phase all contain ammonium saline solution;

[0075] (2) preparing blank liposomes whose inner water phase contains an ammonium salt solution and whose outer water phase contains a physiological isotonic solution;

[0076] (3) Mix the blank liposome obtained in step (2) with dasatinib soluble saline solution, incubate, remove free dasatinib soluble salt, and obtain dasatinib liposome.

[0077] In step (1) and step (2), the concentration of the ammonium salt in the ammonium salt aqueous solution may be 50-500 mM. The concentration of the ammonium salt in the ammonium salt aqueous solution may also be 50-300 mM. The concentration of the ammonium salt in the ammonium salt aqueous solution may also be 300-500 mM.

[0078] The...

Embodiment 1

[0095] Embodiment 1, establish dasatinib detection method

[0096] In this embodiment, a standard curve of dasatinib was established, as follows.

[0097] Using ultraviolet (ultraviolet, UV) detection and analysis method: the detection instrument is TECAN 200PRO; the detection wavelength is 325nm; the detection temperature is 24°C; the detection orifice plate is 96well plates, UV-transparent; the detection volume is 200μl.

[0098] Accurately weigh 2.5002mg of dasatinib hydrochloride and dissolve it in a 25ml volumetric flask to obtain a dasatinib hydrochloride aqueous solution with a concentration of 0.1000mg / ml; mix the dasatinib hydrochloride aqueous solution with ultrapure water, Gradual dilution to obtain a series of dasatinib hydrochloride standard solutions with concentrations of 25 μg / ml, 20 μg / ml, 15 μg / ml, 10 μg / ml, 7.5 μg / ml, 5 μg / ml, and 2.5 μg / ml. The dasatinib hydrochloride standard solution of the above-mentioned concentration was detected by UV detection a...

Embodiment 2

[0102] Embodiment 2, investigate the precipitation reaction of different salt solutions and dasatinib

[0103] Sodium citrate, sodium acetate, sodium sulfate, sodium chloride, ammonium sulfate, ammonium phosphate, ammonium chloride, and ammonium acetate used in this example were all purchased from Sinopharm Chemical Reagent Co., Ltd.; Ammonium isethionate and ammonium isethionate were purchased from Sigma-Aldrich.

[0104] This embodiment investigates the precipitation reaction of sodium salt solution and dasatinib, and the specific process is as follows:

[0105] (1) Precisely weigh 0.8823g sodium citrate and dissolve in 10ml double distilled water (ddH 2 (2) in, obtain the sodium citrate aqueous solution that concentration is 300mM; Accurately weigh 5.06mg dasatinib hydrochloride and be dissolved in the sodium citrate aqueous solution of 1ml 300mM;

[0106] (2) Precisely weigh 0.4082g sodium acetate and dissolve in 10ml ddH 2 In O, obtain the sodium acetate aqueous soluti...

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Abstract

The invention relates to a dasatinib liposome preparation and a preparation method thereof. The liposome preparation of dasatinib provided by the present invention has good biocompatibility, can carry out targeted modification, and can realize the slow and controlled release of dasatinib, which is beneficial to maintain a higher blood drug level for a longer period of time. concentration, improve drug distribution, and increase drug bioavailability. The present invention utilizes the characteristic that dasatinib has better lipophilicity and can pass through the phospholipid bilayer in molecular form and enter the internal water phase; the pH in the water phase in the liposome is low, and the molecules of dasatinib bind hydrogen ions Form dasatinib ion, and then form an insoluble salt with the anion in the ammonium salt solution, so that dasatinib in the inner water phase will not diffuse into the outer water phase, so as to achieve stable encapsulation of dasatinib in the lipid The purpose of the aqueous phase in the plastid; and improve the encapsulation efficiency, storage stability and obtain a good in vitro sustained release effect.

Description

technical field [0001] The invention relates to the technical field of nano drug delivery, in particular to a dasatinib liposome preparation and a preparation method thereof. Background technique [0002] Dasatinib (dasatinib), the chemical name is N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]- 2-Methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide monohydrate is a tyrosine protein kinase inhibitor. Dasatinib is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with chronic, accelerated, myeloid or lymphoid chronic myelogenous leukemia ( Chronic myelogenous leukemia (CML), mainly inhibits the excessive proliferation of white blood cells in the bone marrow of patients, and is often used to treat leukemia caused by BCR-ABL kinase mutations. [0003] The currently marketed dasatinib products are only oral tablets. For patients with Ph+ chronic phase CML, the recommended starting dose is 100 mg once a day. As an oral tab...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K31/506A61K47/04A61K47/20A61P35/00
CPCA61K9/0019A61K9/1271A61K9/1278A61K31/506A61K47/02A61K47/20
Inventor 魏晓慧缪旭光徐宇虹
Owner SHANGHAI JIAOTONG UNIV
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