IP Library Granted Patent US 10,336,679
Granted Patent B2
US 10,336,679 · App. 15/452,137 · Granted Jul 2, 2019

Polymorphic forms of sodium benzoate and uses thereof

Inventors: Guochuan Emil Tsai (Pasadena, CA); Ching-Cheng Wang (New Taipei, TW); Tien-Lan Hsieh (New Taipei, TW)
Assignee: SyneuRx International (Taiwan) Corp.
C07C63/08A23L33/16A61K31/192A61K45/06C07C51/41C07C51/43A23V2002/00C07B2200/13
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Quick Facts
Patent No.
US 10,336,679
App. No.
15/452,137
Granted
Jul 2, 2019
Kind
B2
Abstract

The present disclosure provides polymorphic forms of sodium benzoate with a X-ray diffraction pattern comprising characteristic peaks at a reflection angle 2θ of approximately 5.9, 30.2, and 31.2 degrees; or a X-ray diffraction pattern comprising characteristic peaks at a reflection angle 2θ of approximately 3.7, 5.9, and 26.6 degrees. Also provided herein are methods of preparing the polymorphic forms of sodium benzoate and uses thereof in treating and/or reducing the risk for a neuropsychiatric disorder (e.g., schizophrenia, psychotic disorders, depressive disorders, or Alzheimer's disease).

Claims (12)

1. A polymorphic form of sodium benzoate, which has an X-ray diffraction pattern comprising characteristic peaks at a reflection angle 2θ of approximately 5.9, 30.2, and 31.2 degrees, wherein the X-ray diffraction pattern further comprises characteristic peaks at a reflection angle 2θ of approximately 4.3, 7.1, 8.6, 10.1, 10.7, 12.9, 13.8, 14.4, 17.2, 17.7, 18.5, 21.5, 22.0, 22.6, 23.7, 25.1, 25.9, 26.2, 26.9, 27.9, 28.2, 28.8, 29.1, 29.7, 33.2, 34.9, 35.8, 36.1, and 39.3 degrees, and wherein the polymorphic form of sodium benzoate has a water solubility of 666 mg/ml at ambient temperature.

2. A composition, comprising (i) an effective amount of the polymorphic form of sodium benzoate of claim 1 and (ii) a pharmaceutically acceptable carrier, excipient, diluent, binder, additive, filler, or lubricant, or a mixture thereof.

3. The composition of claim 2 , further comprising a neuropharmaceutical.

4. The composition of claim 3 , wherein the neuropharmaceutical is selected from the group consisting of cariprazine, brexpiprazole, butyrophenone, phenothiazine, fluphenazine, perphenazine, prochlorperazine, thioridazine, trifluoperazine, mesoridazine, promazine, triflupromazine, levomepromazine, promethazine, thioxanthene, chlorprothixene, flupenthixol, thiothixene, zuclopenthixol, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisulpride, asenapine, paliperidone, aripiprazole, lamotrigine, tetrabenazine, cannabidiol, LY2140023, droperidol, pimozide, butaperazine, carphenazine, remoxipride, piperacetazine, sulpiride, acamprosate, tetrabenazine, vilazodone, levomilnacipran, vortioxetine, fluoxetine, paroxetine, escitalopram, citalopram, sertraline, fluvoxamine, venlafaxine, milnacipram, duloxetine, mirtazapine, mianserin, reboxetine, bupropion, amitriptyline, nortriptiline, protriptyline, desipramine, trimipramine, amoxapine, clomipramine, desipramine, doxepin, isocarboxazid, tranylcypromine, selegiline, trazodone, nefazodone, phenelzine, lamatrogine, lithium, topiramate, gabapentin, carbamazepine, oxacarbazepine, valporate, maprotiline, mirtazapine, brofaromine, gepirone, moclobemide, isoniazid, iproniazid, a statin, an amphetamine, modafinil, desoxyn, methamphetamine, cocaine, arecoline, dexmethylphenidate, dextroamphetamine, methylphenidate, lisdexamfetamine dimesylate, mixed salts amphetamine, atomoxetine, clonidine hydrochloride, guanfacine hydrochloride, arecoline, pemoline, donepezil, tacrine, rivastigmine, memantine, physostigmine, lithium salts, nicotine, arecoline, huperzine alpha, selegiline, riluzole, sarcosine, vitamin C, vitamin E, carotenoids, tannic acid, and Ginkgo Biloba extract.

5. The composition of claim 3 , wherein the polymorphic form of sodium benzoate and the neuropharmaceutical in the composition are at a ratio of 1:1 to 100:1 by weight.

6. The composition of claim 4 , wherein the neuropharmaceutical is clozapine, donepezil, sarcosine, or tannic acid.

7. The composition of claim 2 , wherein the composition is a pharmaceutical composition, a nutraceutical composition, a health food, or a medical food.

8. A polymorphic form of sodium benzoate, which is prepared by a process comprising (i) fully dissolving sodium benzoate in water followed by gradual addition of isopropyl alcohol to form a slurry, wherein the isopropyl alcohol and water are in a volume ratio of 5:1, (ii) stirring the slurry for 3 to 4 days to produce the polymorphic form of sodium benzoate, and (iii) filtering and collecting the solid thus formed.

9. A composition comprising (i) an effective amount of the sodium benzoate polymorphic form of claim 8 , and (ii) a pharmaceutically acceptable carrier, excipient, diluent, binder, additive, filler, or lubricant, or a mixture thereof.

10. The composition of claim 9 , further comprising a neuropharmaceutical.

11. The composition of claim 10 , wherein the neuropharmaceutical is selected from the group consisting of cariprazine, brexpiprazole, butyrophenone, phenothiazine, fluphenazine, perphenazine, prochlorperazine, thioridazine, trifluoperazine, mesoridazine, promazine, triflupromazine, levomepromazine, promethazine, thioxanthene, chlorprothixene, flupenthixol, thiothixene, zuclopenthixol, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisulpride, asenapine, paliperidone, aripiprazole, lamotrigine, tetrabenazine, cannabidiol, LY2140023, droperidol, pimozide, butaperazine, carphenazine, remoxipride, piperacetazine, sulpiride, acamprosate, tetrabenazine, vilazodone, levomilnacipran, vortioxetine, fluoxetine, paroxetine, escitalopram, citalopram, sertraline, fluvoxamine, venlafaxine, milnacipram, duloxetine, mirtazapine, mianserin, reboxetine, bupropion, amitriptyline, nortriptiline, protriptyline, desipramine, trimipramine, amoxapine, clomipramine, desipramine, doxepin, isocarboxazid, tranylcypromine, selegiline, trazodone, nefazodone, phenelzine, lamatrogine, lithium, topiramate, gabapentin, carbamazepine, oxacarbazepine, valporate, maprotiline, mirtazapine, brofaromine, gepirone, moclobemide, isoniazid, iproniazid, a statin, an amphetamine, modafinil, desoxyn, methamphetamine, cocaine, arecoline, dexmethylphenidate, dextroamphetamine, methylphenidate, lisdexamfetamine dimesylate, mixed salts amphetamine, atomoxetine, clonidine hydrochloride, guanfacine hydrochloride, arecoline, pemoline, donepezil, tacrine, rivastigmine, memantine, physostigmine, lithium salts, nicotine, arecoline, huperzine alpha, selegiline, riluzole, sarcosine, vitamin C, vitamin E, carotenoids, tannic acid, and Ginkgo Biloba extract.

12. The composition of claim 9 , wherein the composition is a pharmaceutical composition, a nutraceutical composition, a health food, or a medical food.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 23, 2025
From: SYNEURX INTERNATIONAL (TAIWAN) CORP.
To: SYNEURX NEUROSCIENCE
Reel/Frame 072648/0692 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 12, 2018
From: TSAI, GUOCHUAN EMIL
To: SYNEURX INTERNATIONAL (TAIWAN) CORP.
Reel/Frame 047477/0656 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 27, 2017
From: SYNEURX INTERNATIONAL (TAIWAN) CORP.
To: TSAI, GUOCHUAN EMIL
Reel/Frame 043966/0183 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 2, 2017
From: TSAI, GUOCHUAN EMIL; WANG, CHING-CHENG; HSIEH, TIEN-LAN
To: SYNEURX INTERNATIONAL (TAIWAN) CORP.
Reel/Frame 042204/0573 →
Continuity (3)
Provisional Application 62412160 · Oct 24, 2016
Related Publication 20180111891A1 · Apr 26, 2018
Related Publication 20180346400A9 · Dec 6, 2018