Lurasidone pamoate amorphous substance as well as preparation method and application thereof

A technology of lurasidone pamoic acid and lurasidone hydrochloride, which is applied in the field of amorphous pamoic acid lurasidone and its preparation, can solve the problems of low oral bioavailability, low solubility, poor water solubility, etc. , to improve oral bioavailability, improve solubility and avoid irritation

Active Publication Date: 2020-07-28
HUBEI UNIV OF CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The purpose of the present invention is to overcome the problems of poor water solubility and low solubility of lurasidone hydrochloride in the prior art, resulting in low oral bioavailability, and to provide a pamoic acid lurasidone amorphous and its preparation method and application

Method used

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  • Lurasidone pamoate amorphous substance as well as preparation method and application thereof
  • Lurasidone pamoate amorphous substance as well as preparation method and application thereof
  • Lurasidone pamoate amorphous substance as well as preparation method and application thereof

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preparation example Construction

[0041] The second aspect of the present invention provides a method for preparing pamoic acid lurasidone amorphous, the method comprising the following steps:

[0042] (1) dissolving lurasidone hydrochloride and pamoic acid disodium salt, or lurasidone and pamoic acid in tetrahydrofuran to obtain a first mixed solution;

[0043] (2) stirring the first mixed solution at 55-60° C. for 2-3 hours to react to obtain a second mixed solution;

[0044] (3) The second mixed solution was rotary evaporated at 55-60° C. until the solvent was spin-dried, and then water was used as the precipitation solvent for precipitation to obtain lurasidone pamoic acid amorphous substance.

[0045] In the method of the present invention, in step (1), the molar ratio of lurasidone hydrochloride and pamoic acid disodium salt is 1:2-2.5; Specifically, for example, it can be 1:2, 1: 2.1, 1:2.2, 1:2.3, 1:2.4 or 1:2.5; preferably, in step (1), the molar ratio of lurasidone hydrochloride to pamoic acid disod...

Embodiment 1

[0058] Dissolve lurasidone hydrochloride and pamoic acid disodium salt with a molar ratio of 1:2 in 20ml of tetrahydrofuran, stir and react at 60°C for 2h, then spin evaporate to dry the solvent. Add 10ml of water for precipitation, and filter to obtain the first amorphous product A1 after precipitation of crystals.

Embodiment 2

[0060] Lurasidone and pamoic acid with a molar ratio of 1:1 were dissolved in 20ml of tetrahydrofuran, stirred and reacted at 55°C for 3h, and then evaporated to dry the solvent. Add 10ml of water for precipitation, and filter to obtain the second amorphous product A2 after precipitation of crystals.

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Abstract

The invention relates to the technical field of medicines, and discloses a lurasidone pamoate amorphous substance as well as a preparation method and application thereof. The method comprises the following steps: (1) dissolving lurasidone hydrochloride and pamoic acid disodium salt, or lurasidone and pamoic acid in tetrahydrofuran to obtain a first mixed solution; (2) stirring for 2 to 3 h at 55 to 60 DEG C for reaction to obtain a second mixed solution; and (3) carrying out spin-drying on the second mixed solution at 55-60 DEG C, and carrying out precipitation by taking water as a precipitation solvent. The pamoic acid lurasidone amorphous substance prepared by the preparation method is different from lurasidone hydrochloride in the prior art in form; the equilibrium solubility of the first amorphous substance and the second amorphous substance of the pamoic acid lurasidone prepared by the method is 50.69-635 [mu]g / mL and 29-361 [mu]g / mL respectively between pH 6-7.8, so that the solubility of lurasidone hydrochloride can be remarkably improved, and the oral bioavailability of lurasidone is improved.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to an amorphous pamoic acid lurasidone and its preparation method and application. Background technique [0002] Lurasidone (lurasidone) is an atypical antipsychotic drug, which is a class of antipsychotic drugs with dual effects, and has a high affinity for 5-HT2A receptors and dopamine D2 receptors. Compared with classic antipsychotics, lurasidone is less likely to cause EPS, has wider indications, less toxic and side effects, and can improve patients' cognition. It has been used as a first-line antipsychotic drug. In clinical preparations, lurasidone mainly exists in the form of its hydrochloride. Lurasidone hydrochloride (Lurasidonehydrochloride, LH) is a BSC Ⅱ drug with poor solubility, and its oral bioavailability after meals in adults is only 9 -19%. Moreover, the solubility of LH is also pH-dependent, with a maximum solubility at pH 3.8, and then with the increase of pH, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D417/12C07C65/11C07C51/43C07C51/41A61K31/496A61P25/00
CPCA61P25/00C07B2200/13C07C65/11C07D417/12
Inventor 卢山胡寒阳
Owner HUBEI UNIV OF CHINESE MEDICINE
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