CA2750028C – May 7, 2019 – SORBIC AND BENZOIC ACID AND DERIVATIVES THEREOF ENHANCE THE ACTIVITY OF A NEUROPHARMACEUTICAL

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Inventors :

TSAI, GUOCHUAN EMIL

Owner :

LOS ANGELES BIOMEDICAL RESEARCH INSTITUTE AT HARBOR-UCLA MEDICAL CENTER

Application Number :

CA2750028

Document Number :

CA2750028C

Priority Date :

January 20, 2009

Filing Date :

January 19, 2010

Date of Grant/ Publication :

May 7, 2019

Class :

; A61K31 / 192; A61K31 / 19; A61P25 / 18; A61K31 / 519; A61K31 / 551

Abstract

Methods and compositions are provided for treating neuropsychiatric disorders such as schizophrenia, depression, attention deficit disorder, mild cognitive impairment, dementia, and bipolar disorder. The methods entail administering to a patient diagnosed as having a neuropsychiatric disorder (e.g., schizophrenia, depression, attention deficit disorder, mild cognitive impairment, dementia bipolar disorder, etc.) or as at risk for a neuropsychiatric disorder a benzoic acid, benzoic acid salt, and/or benzoic acid derivative, and/or a sorbic acid, sorbic acid salt, and/or sorbic acid derivative, in combination with a neuropharmacological agent (e.g., an antipsychotic, an antidepressant, medications for attention deficit and hyperactivity disorder, cognitive impairment, or dementia, etc.) where the benzoic acid, benzoic acid salt, or benzoic acid derivative, and/or a sorbic acid, sorbic acid salt, and/or sorbic acid derivative, is in an amount sufficient to increase the efficacy of the neuropharmacological agent.

Claim(s)

1. A pharmaceutical composition comprising: a benzoic acid , benzoic acid salt, benzoic acid ester, or derivative thereof and/or a sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof; and a neuropharmaceutical, wherein said benzoic acid, benzoic acid salt, benzoic acid ester or derivative thereof and/or said a sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof is present in an amount sufficient to increase the efficacy of said a neuropharmaceutical drug.;
2. The composition of claim 1, wherein said benzoic acid, a benzoic acid salt, benzoic acid ester, or derivative thereof and/or a sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof comprises a benzoic acid, a benzoic acid salt, a benzoic acid ester, and/or a benzoic acid derivative.;
3. The composition according to claim 2, wherein said a benzoic acid, a benzoic acid salt, a benzoic acid ester, and/or benzoic acid derivative is a benzoic acid salt.;
4. The composition according to claim 2, wherein said a benzoic acid, a benzoic acid salt, a benzoic acid ester, and/or benzoic acid derivative is selected from the group consisting of benzoic acid, sodium benzoate, potassium benzoate, calcium benzoate, , 2-aminobenzoate, 3-aminobenzoate, and 4-aminobenzoate.;
5. The composition of claim 1, wherein said benzoic acid, a benzoic acid salt, benzoic acid ester, or derivative thereof and/or a sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof comprises a sorbic acid, a sorbic acid salt, a sorbic acid ester, and/or a sorbic acid derivative.;
6. The composition according to claim 5, wherein said a sorbic acid, a sorbic acid salt, a sorbic acid ester, and/or sorbic acid derivative is a sorbic acid salt.;
7. The composition according to claim 5, wherein said a sorbic acid, a sorbic acid salt, a sorbic acid ester, and/or sorbic acid derivative is selected from the group consisting of sorbic acid, sodium sorbate, potassium sorbate, calcium sorbate, sorbohydroxamic acid, a sorbic aldehyde, a sorbic acid-thiol adduct, 8- quinolinylsorbate, and m-nitrosorbanilide.;
8. The composition according to any one of claims 1-7, wherein the ratio of benzoic acid, benzoic acid salt, or benzoic acid derivative and/or sorbic acid, sorbic acid salt, or sorbic acid derivative to neuropharmaceutical is stoichiometrically greater than 2:1.;
9. The composition according to any one of claims 1-7, wherein the ratio of benzoic acid, benzoic acid salt, or benzoic acid derivative and/or sorbic acid, sorbic acid salt, or sorbic acid derivative to neuropharmaceutical is stoichiometrically greater than greater than 3:1.;
10. The composition according to any one of claims 1-7, wherein the ratio of benzoic acid, benzoic acid salt, or benzoic acid derivative and/or sorbic acid, sorbic acid salt, or sorbic acid derivative to neuropharmaceutical is stoichiometrically greater than greater than 5:1.;
11. The composition according to any one of claims I-10, wherein said neuropharmaceutical is selected from the group consisting of an antidepressant, an antipsychotic, a phsychostimulant, a mood stablizer, an anxiolytic, ADHD therapeutic, and an Alzheimer’s disease therapeutic.;
12. The composition of claim 11, wherein said neuropharmaceutical is an antipsychotic drug.;
13. The composition of claim 12, wherein said antipsychotic drug is risperidone.;
14. The composition of claim 12, wherein said antipsychotic drug is olanzapine.;
15. The composition of claim 12, wherein said antipsychotic drug is selected from the group consisting of 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, a dopamine partial agonist (BIFEPRUNOX(D, NORCLOZAPINE® (ACP-104)), lamotrigine, memantine, tetrabenazine, cannabidiol, LY2140023, Droperidol, Pimozide, Butaperazine, Carphenazine, Remoxipride, Piperacetazine, Sulpiride, acamprosate, and tetrabenazine (XENAZINE®, NITOMAN®).;
16. The composition of claim 11, wherein said neuropharmaceutical is an antidepressant or mood stabilizer drug.;
17. The composition of claim 16, wherein said neuropharmaceutical is an antidepressant drug selected from the group consisting of a monoamine oxidase inhibitor (MAOI), a tricyclic antidepressant (TCA), a tetracyclic antidepressant (TeCA), a selective serotonin reuptake inhibitor (SSRI), a noradrenergic and specific serotonergic antidepressant (NASSA), a norepinephrine (noradrenaline) reuptake inhibitor, a norepinephrine-dopamine reuptake inhibitor, and a serotonin-norepinephrine reuptake inhibitor (SNRI).;
18. The composition of claim 16, wherein said neuropharmaceutical is an antidepressant drug or mood stabilizer selected from the group consisting of a fluoxetine , paroxetine, escitalopram, citalopram, seriraline, fluvoxamine, venlafaxine, milnacipram, duloxetine, mirtazapine, mianserin, reboxetine, bupropion, amitriptyline, nortriptiline, protriptyline, desipramine, trimipramine, amoxapine, bupropion, bupropion sr, s-citalopram, clomipramine, desipramine, doxepin, isocarboxazid, velafaxine xr, tranylcypromine, trazodone, nefazodone, pheneizine, lamatrogine, lithium, topiramate, gabapentin, carbamazepine, oxacarbazepine, valporate, maprotiline, mirtazapine, brofaromine, gepirone, moclobemide, isoniazid, and iproniazid.;
19. The composition of claim 11, wherein said neuropharmaceutical is an ADHD medication.;
20. The composition of claim 19, wherein said neuropharmaceutical is an ADHD medication selected from the group consisting of a statin, an amphetamine, Modafinit, Desoxyn, Methamphetamine, cocaine, arecoline, Dexmethylphenidate (Focalin, Focalin XR), dextroamphetamine (Dexedrine, Dexedrine Spansules, Dextroamphetamine ER, Dextrostat), methylphenidate (Concerta, Daytrana, Metadate CD, Metadate ER, Methylin, Methylin ER, Ritalin, Ritalin-LA, Ritalin-SR), lisdexamfetamine dimesylate (Vyvanse), mixed salts amphetamine (Adderall, Adderall XR), Atomoxetine (Strattera), clonidine hydrochloride (Catapres), guanfacine hydrochloride (Tenex), arecoline, and Pemoline.;
claim 21: 21. The composition of claim 11, wherein said neuropharmaceutical is a medication for improving cognition and/or inhibiting neurodegeneration.;
claim 22: 22. The composition of claim 21, wherein said medication for improving cognition and/or inhibiting neurodegeneration is selected from the group consisting of Aricept, Donepezil, Tacrine, Rivastigmine, memantine (AXURA®, AKATINOL®, NAMENDA®, EBIXA®, ABIXA®), Physostigmine, Nicotine, arecoline, Huperzine Alpha, Selegiline, riluzole (RILUTEK®), vitamine C, vitamine E, Carotenoids, Ginkgo Biloba.;
claim 23: 23. The composition of claim 21, wherein said medication for improving cognition and/or inhibiting neurodegeneration is memantine.;
claim 24: 24. A method of mitigating one or more symptoms of a neuropsychiatric disorder, said method comprising administering to a subject in need thereof a benzoic acid, benzoic acid salt, or benzoic acid derivative and/or a sorbic acid, sorbic acid salt, or sorbic acid derivative in an amount sufficient to mitigate said one or more symptoms of a neuropsychiatric disorder.;
claim 25: 25. The method of claim 25, wherein said method comprises: administering to said subject said benzoic acid, benzoic acid salt, or benzoic acid derivative and/or a sorbic acid, sorbic acid salt, or sorbic acid derivative in conjunction with a neuropharmaceutical, where the benzoic acid, benzoic acid salt, or benzoic acid derivative and/or a sorbic acid, sorbic acid salt, or sorbic acid derivative is administered in an amount sufficient to increase the efficacy of said neuropharmaceutical.;
claim 26: 26. The method of claim 25, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, or derivative thereof and/or a sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof and said neuropharmaceutical are administered simultaneously.;
claim 27: 27. The method of claim 26, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, or derivative thereof and/or a sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof and said neuropharmaceutical are administered in a combined formulation.;
claim 28: 28. The method of claim 26, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, or derivative thereof and/or a sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof is administered before said neuropharmaceutical.;
claim 29: 29. The method of claim 26, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, or derivative thereof and/or a sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof is administered after said neuropharmaceutical.;
claim 30: 30. The method according to any one of claims 25-29, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, or derivative thereof and/or a sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof comprises a benzoic acid, a benzoic acid salt, a benzoic acid ester, and/or a benzoic acid derivative.;
claim 31: 31. The method according to claim 30, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, and/or benzoic acid derivative is a benzoic acid salt.;
claim 32: 32. The method according to claim 30, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, and/or benzoic acid derivative is selected from the group consisting of benzoic acid, sodium benzoate, potassium benzoate, calcium benzoate, 2-aminobenzoate, 3-aminobenzoate, and 4-aminobenzoate.;
claim 33: 33. The method according to any one of claims 25-29, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, or derivative thereof and/or sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof comprises a sorbic acid, a sorbic acid salt, a sorbic acid ester, and/or a sorbic acid derivative.;
claim 34: 34. The method according to claim 33, wherein said sorbic acid, sorbic acid salt, sorbic acid ester, and/or sorbic acid derivative is a sorbic acid salt.;
claim 35: 35. The method according to claim 33, wherein said sorbic acid, sorbic acid salt, sorbic acid ester, and/or sorbic acid derivative is selected from the group consisting of sorbic acid, sodium sorbate, potassium sorbate, calcium sorbate, sorbohydroxamic acid, a sorbic aldehyde, a sorbic acid-thiol adduct, 8- quinolinylsorbate, and m-nitrosorbanilide.;
claim 36: 36. The method according to any one of claims 25-35, wherein the ratio of benzoic acid, benzoic acid salt, or benzoic acid derivative and/or sorbic acid, sorbic acid salt, or sorbic acid derivative to neuropharmaceutical is stoichiometrically greater than 2:1.;
claim 37: 37. The method according to any one of claims 25-35, wherein the ratio of benzoic acid, benzoic acid salt, or benzoic acid derivative and/or sorbic acid, sorbic acid salt, or sorbic acid derivative to neuropharmaceutical is stoichiometrically greater than greater than 3:1.;
claim 38: 38. The method according to any one of claims 25-35, wherein the ratio of benzoic acid, benzoic acid salt, or benzoic acid derivative and/or sorbic acid, sorbic acid salt, or sorbic acid derivative to neuropharmaceutical is stoichiometrically greater than greater than 5:1.;
claim 39: 39. The method according to any one of claims 25-38, wherein said neuropharmaceutical is selected from the group consisting of an antidepressant, an antipsychotic, a phsychostimulant, a mood stablizer, an anxiolytic, ADHD therapeutic, and an Alzheimer’s disease therapeutic.;
claim 40: 40. The method of claim 39, wherein said neuropsychiatric disorder is a neuropsychiatric disorder characterized by psychosis and said neuropharmaceutical is an antipsychotic drug.;
claim 41: 41. The method of claim 40, wherein said antipsychotic drug is risperidone.;
claim 42: 42. The method of claim 40, wherein said antipsychotic drug is olanzapine.;
claim 43: 43. The method of claim 40, wherein said antipsychotic drug is selected from the group consisting of butyrophenone, phenothiazine, fluphenazine, perphenazine, prochlorperazine, thioridazine, trifluoperazine, mesoridazine, promazine, triflupromazine, levomepromazine, promethazine, thioxanthene, chlorprothixene, flupenthixol, thiothixene, zuclopenthixol, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisuipride, asenapine, paliperidone, aripiprazole, a dopamine partial agonist (BIFEPRUNOX®, NORCLOZAPINE® (ACP-104)), lamotrigine, memantine, tetrabenazine, cannabidiol, LY2140023, Droperidol, Pimozide, Butaperazine, Carphenazine, Remoxipride, Piperacetazine, Sulpiride, acamprosate, and tetrabenazine (XENAZINE®, NITOMAN®).;
claim 44: 44. The method of claim 39, wherein said neuropsychiatric disorder is depression and said neuropharmaceutical is an mood stabilizer and/or antidepressant drug.;
claim 45: 45. The method of claim 44, wherein said neuropharmaceutical is a mood stabilizer and/or antidepressant drug selected from the group consisting of a monoamine oxidase inhibitor (MAOI), a tricyclic antidepressant (TCA), a tetracyclic antidepressant (TeCA), a selective serotonin reuptake inhibitor (SSRI), a noradrenergic and specific serotonergic antidepressant (NASSA), a norepinephrine (noradrenaline) reuptake inhibitor, a norepinephrine-dopamine reuptake inhibitor, and a serotonin-norepinephrine reuptake inhibitor (SNRI).;
claim 46: 46. The method of claim 44, wherein said mood stabilizer and/or antidepressant drug is selected from the group consisting of a fluoxetine , paroxetine, escitalopram, citalopram, sertraline, fluvoxamine, venlafaxine, milnacipram, duloxetine, mirtazapine, mianserin, reboxetine, bupropion, amitriptyline, nortriptiline, protriptyline, desipramine, trimipramine, amoxapine, bupropion, bupropion sr, s-citalopram, clomipramine, desipramine, doxepin, isocarboxazid, velafaxine xr, tranylcypromine, trazodone, nefazodone, phenelzine, lamatrogine, lithium, topiramate, gabapentin, carbamazepine, oxacarbazepine, valporate, maprotiline, mirtazapine, brofaromine, gepirone, moclobemide, isoniazid, and iproniazid.;
claim 47: 47. The method of claim 39, wherein said neuropsychiatric disorder is attention deficit hyperactivity disorder and said neuropharmaceutical is an ADHD medication.;
claim 48: 48. The method of claim 47, wherein said ADHD medication is selected from the group consisting of a statin, an amphetamine, Modafinil, Desoxyn, Methamphetamine, cocaine, arecoline, Dexmethylphenidate (Focalin, Focalin XR), dextroamphetamine (Dexedrine, Dexedrine Spansules, Dextroamphetamine ER, Dextrostat), methylphenidate (Concerta, Daytrana, Metadate CD, Metadate ER, Methylin, Methylin ER, Ritalin, Ritalin-LA, Ritalin-SR), lisdexamfetamine dimesylate (Vyvanse), mixed salts amphetamine (Adderall, Adderall XR), Atomoxetine (Strattera), clonidine hydrochloride (Catapres), guanfacine hydrochloride (Tenex), arecoline, and Pemoline.;
claim 49: 49. The method of claim 39, wherein said neuropsychiatric disorder is characterized by a loss in cognition and/or neurodegeneration and said neuropharmaceutical is a medication for improving cognition and/or inhibiting neurodegeneration.;
claim 50: 50. The method of claim 49, wherein said neuropsychiatric disorder is selected from the group consisting of benign forgetfulness, mild cognitive impairment, dementia and Alzheimer’s disorder;
claim 51: 51. The method of claim 49, wherein said medication for improving cognition and/or inhibiting neurodegeneration is selected from the group consisting of Aricept, Donepezil, Tacrine, Rivastigrnine, memantine (AXURA®, AKATINOL®, NAMENDA®, EBIXA®, ABIXA®), Physostigmine, Nicotine, arecoline, Huperzine Alpha, Selegiline, riluzole (RILUTEK®), vitamine C, vitamine E, Carotenoids, Ginkgo Biloba.;
claim 52: 52. The method according to any one of claims 25-51, wherein said subject is a human diagnosed having or as at risk for a neuropsychiatric disorder.;
claim 53: 53. The method according to any one of claims 25-51, wherein said subject is a non-human mammal.;
claim 54: 54. The use of a benzoic acid, benzoic acid salt, or benzoic acid derivative and/or a sorbic acid, sorbic acid salt, or sorbic acid derivative in conjunction with a neuropharmaceutical, in the manufacture of a medicament for the treatment of a neuropsychiatric disorder, wherein the benzoic acid, benzoic acid salt, or benzoic acid derivative and/or a sorbic acid, sorbic acid salt, or sorbic acid derivative is provided in an amount sufficient to increase the efficacy of said neuropharmaceutical.;
claim 55: 55. The use according claim 54, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, or derivative thereof and/or a sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof comprises a benzoic acid, a benzoic acid salt, a benzoic acid ester, and/or a benzoic acid derivative.;
claim 56: 56. The use according to claim 55, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, and/or benzoic acid derivative is a benzoic acid salt.;
claim 57: 57. The use according to claim 55, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, and/or benzoic acid derivative is selected from the group consisting of benzoic acid, sodium benzoate, potassium benzoate, calcium benzoate, 2- aminobenzoate, 3-aminobenzoate, and 4-aminobenzoate.;
claim 58: 58. The use according claim 54, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, or derivative thereof and/or sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof comprises a sorbic acid, a sorbic acid salt, a sorbic acid ester, and/or a sorbic acid derivative.;
claim 59: 59. The use according to claim 58, wherein said sorbic acid, sorbic acid salt, sorbic acid ester, and/or sorbic acid derivative is a sorbic acid salt.;
claim 60: 60. The use according to claim 58, wherein said sorbic acid, sorbic acid salt, sorbic acid ester, and/or sorbic acid derivative is selected from the group consisting of sorbic acid, sodium sorbate, potassium sorbate, calcium sorbate, sorbohydroxamic acid, a sorbic aldehyde, a sorbic acid-thiol adduct, 8-quinolinylsorbate, and m- nitrosorbanilide.;
claim 61: 61. The use according to any one of claims 56-60, wherein the ratio of benzoic acid, benzoic acid salt, or benzoic acid derivative and/or sorbic acid, sorbic acid salt, or sorbic acid derivative to neuropharmaceutical is stoichiometrically greater than 2:1.;
claim 62: 62. The use according to any one of claims 56-60, wherein the ratio of benzoic acid, benzoic acid salt, or benzoic acid derivative and/or sorbic acid, sorbic acid salt, or sorbic acid derivative to neuropharmaceutical is stoichiometrically greater than greater than 3:1.;
claim 63: 63. The use according to any one of claims 56-60, wherein the ratio of benzoic acid, benzoic acid salt, or benzoic acid derivative and/or sorbic acid, sorbic acid salt, or sorbic acid derivative to neuropharmaceutical is stoichiometrically greater than greater than 5:1.;
claim 64: 64. The use according to any one of claims 56-63, wherein said neuropharmaceutical is selected from the group consisting of an antidepressant, an antipsychotic, a phsychostimulant, a mood stablizer, an anxiolytic, ADHD therapeutic, and an Alzheimer’s disease therapeutic.;
claim 65: 65. The use of claim 64, wherein said neuropsychiatric disorder is a neuropsychiatric disorder characterized by psychosis and said neuropharmaceutical is an antipsychotic drug.;
claim 66: 66. The use of claim 65, wherein said antipsychotic drug is risperidone.;
claim 67: 67. The use of claim 65, wherein said antipsychotic drug is olanzapine.;
claim 68: 68. The use of claim 65, wherein said antipsychotic drug is selected from the group consisting of 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, a dopamine partial agonist (BIFEPRUNOX®, NORCLOZAPINE® (ACP-104)), lamotrigine, memantine, tetrabenazine, cannabidiol, LY2140023, Droperidol, Pimozide, Butaperazine, Carphenazine, Rernoxipride, Piperacetazine, Suipiride, acamprosate, and tetrabenazine (XENAZINE®, NITOMAN®).;
claim 69: 69. The use of claim 64, wherein said neuropsychiatric disorder is depression and said neuropharmaceutical is a mood stabilizer and/or antidepressant drug.;
claim 70: 70. The use of claim 69, wherein said neuropharmaceutical is a mood stabilizer and/or antidepressant drug selected from the group consisting a monoamine oxidase inhibitor (MAOI), a tricyclic antidepressant (TCA), a tetracyclic antidepressant (TeCA), a selective serotonin reuptake inhibitor (SSRI), a noradrenergic and specific serotonergic antidepressant (NASSA), a norepinephrine (noradrenaline) reuptake inhibitor, a norepinephrine-dopamine reuptake inhibitor, and a serotonin-norepinephrine reuptake inhibitor (SNRI).;
claim 71: 71. The use of claim 69 wherein said neuropharmaceutical is an antidepressant drug or mood stabilizer selected from the group consisting of a fluoxetine , paroxetine, escitalopram, citalopram, sertraline, fluvoxamine, venlafaxine, milnacipram, duloxetine, mirtazapine, mianserin, reboxetine, bupropion, amitriptyline, nortriptiline, protriptyline, desipramine, trimipramine, amoxapine, bupropion, bupropion sr, s-citalopram, clomipramine, desipramine, doxepin, isocarboxazid, velafaxine xr, tranylcypromine, trazodone, nefazodone, phenelzine, lamatrogine, lithium, topiramate, gabapentin, carbamazepine, oxacarbazepine, valporate, maprotiline, mirtazapine, brofaromine, gepirone, moclobemide, isoniazid, and iproniazid.;
claim 72: 72. The use of claim 64, wherein said neuropsychiatric disorder is attention deficit hyperactivity disorder and said neuropharmaceutical is an ADHD medication.;
claim 73: 73. The use of claim 72, wherein said neuropharmaceutical is an ADHD medication selected from the group consisting of a statin, an amphetamine, Modafmil, Desoxyn, Methamphetamine, cocaine, arecoline, Dexmethylphenidate (Focalin, Focalin XR), dextroamphetamine (Dexedrine, Dexedrine Spansules, Dextroamphetamine ER, Dextrostat), methylphenidate (Concerta, Daytrana, Metadate CD, Metadate ER, Methylin, Methylin ER, Ritalin, Ritalin-LA, Ritalin-SR), lisdexamfetamine dimesylate (Vyvanse), mixed salts amphetamine (Adderall, Adderall XR), Atomoxetine (Strattera), clonidine hydrochloride (Catapres), guanfacine hydrochloride (Tenex), arecoline, and Pemoline.;
claim 74: 74. The use of claim 64, wherein said neuropsychiatric disorder is characterized by a loss in cognition and/or neurodegeneration and said neuropharmaceutical is a medication for improving cognition and/or inhibiting neurodegencration.;
claim 75: 75. The use of claim 74, wherein said neuropsychiatric disorder is selected from the group consisting of benign forgetfulness, mild cognitive impairment, dementia and Alzheimer’s disorder;
claim 76: 76. The use of claim 74, wherein said medication for improving cognition and/or inhibiting neurodegeneration is selected from the group consisting of Aricept, Donepezil, Tacrine, Rivastigmine, memantine (AXURA®, AKATINOL®, NAMENDA®, EBIXA®, ABIXA®), Physostigmine, Nicotine, arecoline, Huperzine Alpha, Selegiline, riluzole (RILUTEK®), vitamine C, vitamine E, Carotenoids, Ginkgo Biloba.;
claim 77: 77. A pharmaceutical formulation comprising a benzoic acid, benzoic acid salt, benzoic acid ester, or benzoic acid derivative and/or a sorbic acid, sorbic acid salt, sorbic acid ester or sorbic acid derivative in an amount effective to mitigate one or more symptoms of a neuropsychiatric disorder.;
claim 78: 78. The formulation of clairn 77, wherein said neuropsychiatric disorder is selected from the group consisting of schizophrenia, depression, attention deficit disorder, mild cognitive impairment, dementia, attention deficit hyperactivity disorder (ADHD), and bipolar disorder.;
claim 79: 79. The formulation of claim 77, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, or derivative thereof and/or a sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof comprises a benzoic acid, a benzoic acid salt, a benzoic acid ester, and/or a benzoic acid derivative.;
claim 80: 80. The formulation of claim 79, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, and/or benzoic acid derivative is a benzoic acid salt.;
claim 81: 81. The formulation of claim 79, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, and/or benzoic acid derivative is selected from the group consisting of benzoic acid, sodium benzoate, potassium benzoate, calcium benzoate, 2- aminobenzoate, 3-aminobenzoate, and 4-aminobenzoate.;
claim 82: 82. The formulation of claim 77, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, or derivative thereof and/or sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof comprises a sorbic acid, a sorbic acid salt, a sorbic acid ester, and/or a sorbic acid derivative.;
claim 83: 83. The formulation of claim 82, wherein said sorbic acid, sorbic acid salt, sorbic acid ester, and/or sorbic acid derivative is a sorbic acid salt.;
claim 84: 84. The formulation of claim 82, wherein said sorbic acid, sorbic acid salt, sorbic acid ester, and/or sorbic acid derivative is selected from the group consisting of sorbic acid, sodium sorbate, potassium sorbate, calcium sorbate, sorbohydroxamic acid, a sorbic aldehyde, a sorbic acid-thiol adduct, 8-quinolinylsorbate, and m- nitrosorbanilide.;
claim 85: 85. The use of a benzoic acid, benzoic acid salt, benzoic acid ester, or benzoic acid derivative and/or a sorbic acid, sorbic acid salt, sorbic acid ester or sorbic acid derivative in the manufacture of a medicament for the treatment of a neuropsychiatric disorder, where the benzoic acid, benzoic acid salt, benzoic acid ester, or benzoic acid derivative and/or a sorbic acid, sorbic acid salt, sorbic acid ester or sorbic acid derivative si present in an amount effective to mitigate one or more symptoms of said neuropsychiatric disorder.;
claim 86: 86. The use according claim 85, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, or derivative thereof and/or a sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof comprises a benzoic acid, a benzoic acid salt, a benzoic acid ester, and/or a benzoic acid derivative.;
claim 87: 87. The use according to claim 86, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, and/or benzoic acid derivative is a benzoic acid salt.;
claim 88: 88. The use according to claim 86, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, and/or benzoic acid derivative is selected from the group consisting of benzoic acid, sodium benzoate, potassium benzoate, calcium benzoate, 2- aminobenzoate, 3-aminobenzoate, and 4-aminobenzoate.;
claim 89: 89. The use according claim 85, wherein said benzoic acid, benzoic acid salt, benzoic acid ester, or derivative thereof and/or sorbic acid, sorbic acid salt, sorbic acid ester, or derivative thereof comprises a sorbic acid, a sorbic acid salt, a sorbic acid ester, and/or a sorbic acid derivative.;
claim 90: 90. The use according to claim 89, wherein said sorbic acid, sorbic acid salt, sorbic acid ester, and/or sorbic acid derivative is a sorbic acid salt.;
claim 91: 91. The use according to claim 89, wherein said sorbic acid, sorbic acid salt, sorbic acid ester, and/or sorbic acid derivative is selected from the group consisting of sorbic acid, sodium sorbate, potassium sorbate, calcium sorbate, sorbohydroxamic acid, a sorbic aldehyde, a sorbic acid-thiol adduct, 8-quinolinylsorbate, and m- nitrosorbanilide.

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