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Vortioxetine semi-hydrochloride, preparation method therefor, and pharmaceutical composition thereof

A technology of vortioxetine and hydrochloride, applied in the field of vortioxetine hemihydrochloride and its preparation, can solve the problems of poor drug stability, easy mutual conversion, unsuitability for preparation development and the like, and achieves stable crystal form, The effect of high crystallinity and simple operation

Inactive Publication Date: 2015-12-02
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Currently commonly used vortioxetine bromide has problems such as easy mutual conversion of crystal forms and moisture absorption, especially the different solubility of vortioxetine hydrobromide in different crystal forms, calculated by vortioxetine base, α type The solubility of the β-form is 2.0mg / mL, and the solubility of the β-form is 1.2mg / mL. Due to the transformation of the crystal form, the preparation may have obvious differences in drug dissolution and bioavailability
Vortioxetine hydrobromide is easy to form solvates, and the existence of solvates often leads to poor stability of the drug, which is not suitable for the development of preparations

Method used

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  • Vortioxetine semi-hydrochloride, preparation method therefor, and pharmaceutical composition thereof
  • Vortioxetine semi-hydrochloride, preparation method therefor, and pharmaceutical composition thereof
  • Vortioxetine semi-hydrochloride, preparation method therefor, and pharmaceutical composition thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Add 4 mL of ethanol solution containing 0.1 g of vortioxetine to one side of the communicating H tube; add 1 mL of concentrated hydrochloric acid with a mass fraction of 38% to the other side of the H tube, and continue to add 3 mL of ethanol. Close the H tube to slowly diffuse the hydrogen chloride gas in the H tube, and obtain white crystals after 72 hours.

[0044] The schematic diagram of the structural unit of the crystal is shown in figure 1 As shown, the powder XRD pattern is as follows figure 2 As shown, the TG diagram is shown as image 3 As shown, the IR diagram is as Figure 4 as shown, 1 H-NMR such as Figure 5 Shown (* represents the characteristic peak of solvent).

Embodiment 2

[0046] Take 10g of vortioxetine and add it to 350mL of acetonitrile, heat and stir to dissolve it completely, and then inject hydrogen chloride gas into the container under stirring until no more weight is added, filter the solid with suction at room temperature, wash with 10mL of acetonitrile and dry to constant weight , Vortioxetine hemihydrochloride white powder 9.8g, the powder diffraction of this solid is consistent with formula (I) Vortioxetine hemihydrochloride.

[0047] 1 H-NMR (d 6-DMSO,δppm):7.33(d,1H),7.24(s,1H),7.07-7.14(m,3H),6.87-7.01(m,1H),6.40(d,1H),3.04(s,8H ), 2.32(s,3H), 2.24(s,3H).

Embodiment 3

[0049] Take 10g of vortioxetine and add it to 250mL of methanol, stir to dissolve it completely, and then inject hydrogen chloride gas into the container until the weight is no longer increased under stirring, filter the solid with suction at room temperature, wash with 10mL of methanol and dry to constant weight. Vortioxetine hemihydrochloride white powder was 9.3 g, and the powder diffraction and thermogravimetric analysis of the solid was consistent with formula (I) vortioxetine hemihydrochloride.

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Abstract

The present invention discloses a vortioxetine semi-hydrochloride, a preparation method therefor, and a pharmaceutical composition thereof. The vortioxetine semi-hydrochloride is as shown in the formula I; a space group of the salt is a monoclinic system; two vortioxetine molecules share one proton; and a hydrogen bond N-H ... Cl- is combined with vortioxetine to form a basic structural unit. The vortioxetine semi-hydrochloride provided by the invention has a stable crystal form and high crystallinity; the preparation method is simple; and the crystal does not contain a solvent.

Description

technical field [0001] The invention belongs to the technical field of medicine and chemical industry, and more specifically relates to vortioxetine hemihydrochloride and a preparation method thereof. Background technique [0002] Vortioxetine hydrobromide, the chemical name is 1-[2-[(2,4-dimethylphenyl) mercapto] phenyl]-piperazine hydrobromide, produced by Lundbeck, Denmark (Lundbeck) Pharmaceutical Company and Japan's Takeda (Takeda) Pharmaceutical Company jointly developed a drug for the treatment of major depressive disorder and generalized anxiety disorder. The drug was approved by the US FDA in September 2013 under the trade name Brintellix. The drug also received final approval in the European Union on December 27, 2013. The active ingredient of vortioxetine hydrobromide is vortioxetine (vortioxetine), which is an inhibitor of 5-hydroxytryptamine transporter, and at the same time regulates the activity of its receptors, and is also a 5-HT3A receptor inhibitor, 5-H...

Claims

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Application Information

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IPC IPC(8): C07D295/096A61K31/495A61P25/22A61P25/24
CPCC07D295/096C07B2200/13
Inventor 张雷何赛飞张硕李晶关溯
Owner SOUTH CHINA UNIV OF TECH
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