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Self-assembly medicine vesicles and construction method thereof

A construction method and self-assembly technology, which is applied in the fields of biomedicine and physical chemistry, can solve problems such as difficult formation of precipitates, and achieve the effects of broadening the scope of research, simple methods, and easy storage

Inactive Publication Date: 2013-03-20
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The limitation of the precipitation method is that molecules with too weak polarity cannot be dissolved in water, while molecules with strong polarity and small molecular weight are extremely difficult to form precipitates after interacting in water

Method used

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  • Self-assembly medicine vesicles and construction method thereof
  • Self-assembly medicine vesicles and construction method thereof
  • Self-assembly medicine vesicles and construction method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Preparation of cytarabine-1,4-bis(2-ethylhexyl)succinate sodium sulfonate (AOT) ion-pair amphiphile self-assembled vesicles

[0047] (1) Accurately weigh 0.5594 g of cytarabine hydrochloride with an analytical balance, add 2 mL of water, the molar concentration is 1 mol / L, and dissolve by ultrasonication for 10 s;

[0048] (2) Accurately weigh 0.8891 g of the surfactant 1,4-bis(2-ethylhexyl) succinate sodium sulfonate (AOT) with an analytical balance and measure 18 mL of water to prepare a molar concentration of 0.1 mol / L, placed in a clean beaker, ultrasonicated for 10 minutes, stirred at 72°C under the action of a magnetic stirrer at a stirring speed of 300 rpm, and stirred for 0.5h until AOT was completely dissolved to obtain an AOT solution;

[0049] (3) Add the AOT solution dropwise to the cytarabine solution at 72°C under the action of a magnetic stirrer at a stirring speed of 200 r / min. The molar ratio of AOT to cytarabine hydrochloride is 1:1, stir for 1 hour ...

Embodiment 2

[0056] Drug-Surfactant Ionic Structure Confirmation

[0057] The Cl in the cytarabine-AOT ion pair (Cytarabine-AOT) prepared in Example 1 was analyzed by silver nitrate precipitation method. - Qualitative detection showed that no precipitate was formed, indicating that the Cytarabine-AOT ion pair (Cytarabine-AOT) no longer contained NaCl.

[0058] NMR 1 The chemical composition of cytarabine-AOT ion pair (Cytarabine-AOT) was confirmed by the method of H spectrum, and the results are as follows figure 1 As shown, the molar ratio of drug to surfactant in ion pairing is 1:1.

[0059] The phase transfer behavior of cytarabine hydrochloride, AOT, cytarabine hydrochloride-AOT ion pair (Cytarabine-AOT) is measured respectively by DSC analysis method, the results are as follows figure 2 As shown, the appearance of new endothermic peaks proves the formation of new substances.

Embodiment 3

[0061] Study on Aggregation Behavior of Cytarabine-AOT

[0062] The molar concentration of the preparation is 10 -5 ~10 -2 A series of ion-pair solutions of mol / L, using a surface tensiometer, 25 ℃, the surface tension of the sample is measured by the hanging method, the results are as follows image 3 As shown, ions have high surface activity to amphiphilic molecules, which can make the surface tension of water from 70mN·m -1 reduced to 26mN·m -1 , with a critical aggregation concentration of about 1×10 -3 mol / L.

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Abstract

The invention discloses self-assembly medicine vesicles and a construction method thereof. The vesicles consist of surfactants and medicine molecules, wherein one surfactant molecule and one medicine molecule are combined to form a medicine-surfactant ion pair with amphipathy, and the ion pairs can form the vesicles in solution in a self-assembly manner. The construction method comprises the following steps of: preparing a medicine solution and a surfactant solution respectively, mixing the two solutions according to an equal molar ratio to form a solution mixture, mixing the two solutions adequately under conditions of heating and stirring, performing freeze drying on the solution mixture to remove moisture, adding a proper organic solvent into dried solids to remove inorganic salt so as to obtain a medicine-surfactant ion pair solution, evaporating the solution in a rotation manner, performing vacuum drying on the solution to remove the organic solvent so as to the obtain the product. Amphiphilic molecules of the ion pairs can form the medicine vesicles in a polar solvent in a self-assembly manner. The construction method is simple and rapid, and the obtained vesicles are uniform in state, small in particle size and good in stability and have wide application prospect in sustained drug release.

Description

technical field [0001] The invention belongs to the fields of biomedicine and physical chemistry, and in particular relates to a drug-surfactant ion pair self-assembled drug vesicle and a construction method. Background technique [0002] In the field of drug application, many active drug molecules have encountered many problems before and during clinical application. For example, the unsatisfactory physical and chemical properties of drugs (poor water solubility, poor permeability, etc.) limit their clinical application; It is very toxic to normal tissues; after the drug reaches the body, it is degraded into inactive or toxic metabolites by the biological process in the body, so that the drug cannot reach the effective therapeutic concentration at the target site. Therefore, the development of suitable drug carriers has become the most economical and effective means to solve this problem. Among many new drug carriers, the bilayer membrane structure of vesicles makes it an ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/48A61K31/7068A61K31/704A61K31/13
Inventor 栾玉霞姜悦杨晓霞
Owner SHANDONG UNIV
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