# US 2019/0169110 A1 · Co-crystals of sodium benzoate and uses thereof

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- Number: US 2019/0169110 A1
- Document ID: US20190169110A1
- Status: Published application
- Kind: A1
- Application number: 16/309,349
- Filed: 2017-06-13
- Published: 2019-06-06
- Earliest claimed: 2016-06-13
- Assignees: SyneuRx International (Taiwan) Corp.
- Applicants: SyneuRx International (Taiwan) Corp.
- Inventors: Guochuan Emil Tsai; Ching-Cheng Wang; Tien-Lan Hsieh; Yuan-Chun Lo
- Web page: https://patentgrep.com/patent/US20190169110A1

## CPC

- C07C 63/08: Salts thereof
- A61P 3/06: Antihyperlipidemics
- A61P 3/08: for glucose homeostasis (pancreatic hormones A61P5/48)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/12: Antihypertensives
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 25/30: for treating abuse or dependence
- C07C 57/10: Sorbic acid
- C07C 57/44: Cinnamic acid
- C07D 213/55: Acids; Esters
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

Provided are co-crystals of a sodium benzoate compound and a co-former compound of Formula (I) Also provided herein are methods of preparing the co-crystals 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) or a glucose or lipid metabolic disorder (e.g., obesity, diabetes, hypercholesterolemia, hypertension, or hyperlipidemia).

## Claims

### Claim 1

A co-crystal of a sodium benzoate compound and a co-former, wherein the co-former is a compound of Formula (I):
in which
L is alkyl, carbocyclyl, C═C, C═C—C═C, C≡C, or absent;
A is alkyl, carbocyclyl, aryl, or heteroaryl; and
X═O or N—B, B being H, alkyl, carbocyclyl, aryl, or heteroaryl.

### Claim 2 (depends on 1)

The co-crystal of claim 1, wherein the sodium benzoate compound and the co-former exist in the co-crystal in a molecular ratio ranging from 1:10 to 10:1.

### Claim 3 (depends on 1)

The co-crystal of claim 1, wherein L is C═C or C═C—C═C, and A is C1-C6 alkyl, aryl, or heteroaryl.

### Claim 4 (depends on 3)

The co-crystal of claim 3, wherein L is C═C—C═C, A is methyl, and X is O.

### Claim 5 (depends on 4)

The co-crystal of claim 4, wherein the sodium benzoate compound and the co-former exist in the co-crystal in a molecular ratio of 1:2.

### Claim 6 (depends on 5)

The co-crystal of claim 5, wherein the co-crystal has a powder X-ray diffraction pattern substantially as depicted in FIG. 2.

### Claim 7 (depends on 4)

The co-crystal of claim 4, wherein the sodium benzoate compound and the co-former exist in the co-crystal in a molecular ratio of 1:1.

### Claim 8 (depends on 7)

The co-crystal of claim 7, wherein the co-crystal has a powder X-ray diffraction pattern substantially as depicted in FIG. 6, and an endothermic peak corresponding to the melting point of about 430° C.

### Claim 9 (depends on 7)

The co-crystal of claim 7, wherein the co-crystal has a powder X-ray diffraction pattern substantially as depicted in FIG. 10.

### Claim 10 (depends on 3)

The co-crystal of claim 3, wherein L is C═C, A is phenyl, and X is O.

### Claim 11 (depends on 10)

The co-crystal of claim 10, wherein the sodium benzoate compound and the co-former exist in the co-crystal in a molecular ratio of 1:2.

### Claim 12 (depends on 11)

The co-crystal of claim 11, wherein the co-crystal has a powder X-ray diffraction pattern substantially as depicted in FIG. 14, and an endothermic peak corresponding to the melting point of about 410° C.

### Claim 13 (depends on 3)

The co-crystal of claim 3, wherein L is absent, A is pyridyl, and X is O.

### Claim 14 (depends on 13)

The co-crystal of claim 13, wherein the sodium benzoate compound and the co-former exist in the co-crystal in the molecular ratio of 1:1.

### Claim 15 (depends on 14)

The co-crystal of claim 14, wherein the co-crystal has a powder X-ray diffraction pattern substantially as depicted in FIG. 19, and an endothermic peak corresponding to the melting point of about 405° C.

### Claim 16 (depends on 1)

A composition, comprising an effective amount of a co-crystal of claim 1 and a carrier.

### Claim 17 (depends on 16)

The composition of claim 16, wherein the composition is a pharmaceutical composition, a nutraceutical composition, a health food, or a medical food.

### Claim 18 (depends on 1)

A method of treating or reducing the risk for a neuropsychiatric disorder in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a co-crystal of claim 1.

### Claim 19 (depends on 18)

The method of claim 18, wherein the neuropsychiatric disorder is selected from the group consisting of schizophrenia, psychotic disorders, Alzheimer's disease, dementia, mild cognitive impairment, benign forgetfulness, closed head injury, autistic spectrum disorder, Asperger's disorder, attention deficit hyperactivity disorders, obsessive compulsive disorder, tic disorders, childhood learning disorders, premenstrual syndrome, depressions, bipolar disorders, anxiety disorders, post-traumatic stress disorder, chronic pain, eating disorders, addiction disorders, personality disorders, Parkinson's disorder, Huntington's disorder and amyotrophic lateral sclerosis.

### Claim 20 (depends on 1)

A method for treating or reducing the risk for a glucose or lipid metabolic disorder, the method comprising administering to a subject in need thereof a therapeutically effective amount of a co-crystal of claim 1.

### Claim 21 (depends on 20)

The method of claim 20, wherein the glucose or lipid metabolic disorder is selected from the group consisting of obesity, diabetes, hypercholesterolemia, hypertension, and hyperlipidemia.

### Claim 22 (depends on 1)

A method for preparing a co-crystal of claim 1, the method comprising:
(i) mixing the sodium benzoate compound and the co-former in a solvent at a temperature of about 40-110° C. to form a saturated solution, wherein the sodium benzoate compound and the co-former are at a molar ratio of 1:10 to 10:1;
(ii) heating and stirring the solution at a temperature of about 70-150° C. to allow formation of the co-crystal;
(iii) collecting the co-crystal formed in (ii).

### Claim 23 (depends on 22)

The method of claim 22, wherein step (i) is performed by adding the solvent in a dropwise manner into the sodium benzoate compound and co-former and stirring the mixture thus formed to allow dissolution of the sodium benzoate compound and co-former in the solvent.

### Claim 24 (depends on 1)

A method for preparing a co-crystal of claim 1, the method comprising:
(i) mixing the sodium benzoate compound and the co-former in a solvent at a temperature of about 40-110° C. to form a saturated solution, wherein the sodium benzoate and the co-former are at a molar ratio of 1:10 to 10:1;
(ii) cooling the solution to room temperature;
(iii) adding a seed co-crystal of the sodium benzoate compound and the co-former into the solution of (ii) to form a mixture;
(iv) placing the mixture at room temperature to allow formation of the co-crystal; and
(v) collecting the co-crystal formed in (iv).

### Claim 25 (depends on 24)

The method of claim 24, wherein step (i) is performed by adding the solvent in a dropwise manner into the sodium benzoate compound and co-former and stirring the mixture thus formed to allow dissolution of the sodium benzoate and co-former in the solvent

### Claim 26 (depends on 1)

A method for preparing a co-crystal of claim 1, the method comprising:
(i) providing a co-crystal of claim 1,
(ii) dissolving the co-crystal in a solvent at a temperature ranging from about 35-100° C. to form a solution;
(iii) stirring the solution at a temperature of about 40-110° C. for a first period to allow formation of the co-crystal; wherein the first period is about 1-10 days; and
(iv) collecting the co-crystal.

### Claim 27 (depends on 26)

The method of claim 26, further comprising, following step (iii), stirring the solution at a temperature of about 40-110° C. for a second period, wherein the second period is about 1-10 days.