# US 2016/0199362 A1 · Method for the treatment, alleviation of symptoms of, relieving, improving and preventing a cognitive disease, disorder or condition

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- Number: US 2016/0199362 A1
- Document ID: US20160199362A1
- Status: Published application
- Kind: A1
- Application number: 15/074,580
- Filed: 2016-03-18
- Published: 2016-07-14
- Earliest claimed: 2009-06-25
- Assignees: Alcobra Ltd.
- Applicants: Alcobra Ltd.
- Inventors: Rina Yamin; Dalia Megiddo; Yaron Ilan
- Web page: https://patentgrep.com/patent/US20160199362A1

## CPC

- A61K 31/4427: containing further heterocyclic ring systems
- A61K 9/0095: {Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006)}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/485: {Inorganic compounds}
- A61K 9/4866: {Organic macromolecular compounds}
- A61K 31/4015: having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
- A61K 31/402: 1-aryl substituted, e.g. piretanide
- A61K 31/4025: not condensed and containing further heterocyclic rings, e.g. cromakalim
- A61K 31/4415: Pyridoxine, i.e. Vitamin B6 (pyridoxal phosphate A61K31/675)
- A61K 31/4418: having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
- A61K 31/4425: Pyridinium derivatives, e.g. pralidoxime, pyridostigmine
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/20: Hypnotics; Sedatives
- 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 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention provides uses of a salt adduct comprising at least one positively charged moiety being a pyridoxine or a derivative thereof and at least one carboxylated 5- to 7-membered lactam ring, optionally additionally substituted, for the preparation of a medicament for the treatment, alleviation of symptoms of, relieving, improving and preventing a cognitive disease, disorder or condition in a subject. Additionally, the invention provides use of said salt adducts for the preparation of medicaments for the improvement of cognitive functions in a healthy subject.

## Claims

### Claim 1

Use of a salt adduct comprising at least one positively charged moiety being a pyridoxine or a derivative thereof and at least one carboxylated 5- to 7-membered lactam ring, optionally additionally substituted, for the preparation of a medicament for the treatment, alleviation of symptoms of, relieving, improving and preventing a cognitive disease, disorder or condition in a subject.

### Claim 2

Use of a salt adduct comprising at least one positively charged moiety being a pyridoxine or a derivative thereof and at least one carboxylated 5- to 7-membered lactam ring, optionally additionally substituted, for the preparation of a medicament for the improvement of cognitive functions in a healthy subject.

### Claim 3 (depends on 1, 2)

Use according to claim 1 or 2, wherein said positively charged moiety is a compound of formula (I):
wherein
R1 is straight or branched C1-C6 alkyl;
R2 is selected from —OH, straight or branched C1-C6 alkoxy, and straight or branched C1-C6 alkoxycarbonyl;
R3 and R4 are each independently selected from formyl, straight or branched C1-C6 alkyl optionally substituted by at least one halogen, amine, hydroxy, C1-C6 alkoxy, thiol and C1-C6 alkoxycarbonyl.

### Claim 4

Use according to any one of the preceding claims, wherein said carboxylated lactam ring is selected from the group consisting of:
wherein
R6 is selected from H, straight or branched C1-C6 alkyl optionally substituted by at least one halogen, straight or branched C2-C6 alkenyl, straight or branched C2-C6 alkynyl, cycloalkyl, aryl and heteroaryl optionally substituted by a C1-C6 alkyl;
R7, R8, R9, R10 R11, R12, R13 and R14 are each independently selected from H, straight or branched C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, aryl and heteroaryl optionally substituted by at least one group selected from C1-C6 alkyl, halogen, amino, cyano, nitro, thiol, C1-C6 alkoxy, aminocarbonyl, C1-C6 alkoxycarbonyl, C1-C6 carboxyalkyl, C1-C6 alkoxycarbonylalkyl and amidino.

### Claim 5

Use according to any one of the preceding claims, wherein said salt adduct is selected from the following:

### Claim 6 (depends on 1)

Use according to claim 1, wherein said cognitive disease, disorder or condition is selected from Attention Deficit/Hyperactivity Disorder (ADHD/ADD), impaired memory (Amnesia), impaired wakefulness, mental fatigue conditions, Shift Work Sleep Disorder, Narcolepsy, Obstructive Sleep Apnea/Hypopnea Syndrome, poor concentration, and poor focus or any combination thereof.

### Claim 7 (depends on 1)

Use according to claim 1, wherein said cognitive disease, disorder or condition is selected from learning disabilities, impairment of memory, cognitive dysfunction, alteration of cognitive function, including Alzheimer's disease, or any type of encephalopathy, including uremic and hepatic encephalopathy.

### Claim 8 (depends on 1)

Use according to claim 1, wherein said cognitive disease, disorder or condition is a neurobehavioral disease, disorder or condition.

### Claim 9 (depends on 8)

Use according to claim 8, wherein said neurobehavioral disease, disorder or condition is selected from Attention Deficit Hyperactivity Disorder (ADHD), Attention Deficit Disorder (ADD), impaired memory, poor concentration, and poor focus.

### Claim 10 (depends on 1)

Use according to claim 1, wherein said cognitive disease, disorder or condition is selected from Attention Deficit Disorder (ADD) or Hyperactivity Disorder (ADHD/ADD), impaired memory (Amnesia), impaired wakefulness, mental fatigue conditions, Shift Work Sleep Disorder, Narcolepsy, Obstructive Sleep Apnea/Hypopnea Syndrome, poor concentration, and poor focus or any combination thereof.

### Claim 11 (depends on 2)

Use according to claim 2, wherein said cognitive function selected from temporary or long term learning disabilities, temporary or long term impairment of memory, temporary or long term cognitive dysfunction, temporary or long term alteration of cognitive function, temporary or long term concentration impairment, temporary or long term focus impairment, temporary or long term impaired wakefulness, temporary or long term mental fatigue conditions, temporary or long term Shift Work Sleep Disorder, or any combination thereof.

### Claim 12

Use according to any one of the preceding claims, wherein said subject is a child, an adolescent, an adult, or an elderly person.

### Claim 13

Use according to any one of the preceding claims, wherein said salt adduct is formulated in a sustained-, delayed or controlled-release dosage form.

### Claim 14

Use according to any one of the preceding claims, wherein said salt adduct is formulated in a sustained-, delayed or controlled-release dosage form combined with a salt adduct formulated in an immediate or burst effect dosage form.

### Claim 15

Use according to any one of the preceding claims, wherein said salt adduct is formulated to deliver up to 0.1-1000 mg/kg body weight/day of said salt adduct, preferably 1-400 mg/kg body weight of said salt adduct, in a single dose administration or portion thereof.

### Claim 16

Use according to any one of the preceding claims, wherein said salt adduct is formulated together with at least one additional pharmaceutically active agent.