Nasal Compositions and Uses Thereof
Pharmaceutical compositions for the treatment of nasal congestion, wherein the pharmaceutical compositions comprise low concentrations of a super-selective subclass of selective α-2 adrenergic receptor agonists. Methods of using the compositions for the treatment of nasal congestion, cerebrovascular disease or systemic conditions, and as delivery vehicles to deliver other active agents to treat systemic or cerebrovascular diseases or conditions.
1 . A nasal spray composition comprising a selective α-2 adrenergic receptor agonist having a binding affinity of 900 fold or greater for α-2 over α-1 adrenergic receptors, or a pharmaceutically acceptable salt thereof, wherein said α-2 adrenergic receptor agonist is present at a concentration from between about 0.001% to about 0.075% weight by volume.
2 . The nasal spray composition of claim 1 , wherein said selective α-2 adrenergic receptor agonist is selected from the group consisting of, brimonidine, alpha methyl dopa, guanfacine, fadolmidine, dexmedetomidine, (+)-(S)-4-[1-(2,3-dimethyl-phenyl)-ethyl]-1,3-dihydro-imidazole-2-thione, 1-[(imidazolidin-2-yi)imino]indazole, and mixtures of these compounds.
3 . The nasal spray composition of claim 1 , wherein said selective α-2 adrenergic receptor agonist is brimonidine.
4 . The nasal spray composition of claim 3 , wherein said brimonidine is at a concentration from between about 0.001% and about 0.05%.
5 . The nasal spray composition of claim 1 , further comprising a mucoadhesive additive.
6 . The nasal spray composition of claim 5 , wherein said mucoadhesive additive is selected from the group consisting of carboxymethylcellulose, hydroxypropylcellulose, other cellulose derivatives, guar gum, xanthan gum, carbomers, poloxamers, chondroitin sulfate and mixtures thereof.
7 . The nasal spray composition of claim 6 , wherein said mucoadhesive additive is Poloxamer 407.
8 . A method of treatment of nasal congestion comprising administering to a patient in need thereof a pharmaceutical composition comprising: a selective α-2 adrenergic receptor agonist having a binding affinity of 900 fold or greater for α-2 over α-1 adrenergic receptors, or a pharmaceutically acceptable salt thereof, wherein said α-2 adrenergic receptor agonist is present at a concentration from between about 0.001% to about 0.075% weight by volume.
9 . The method of claim 8 , wherein said composition is a nasal spray.
10 . The method of claim 8 , further comprising topically ophthalmically administering to said patient said selective α-2 adrenergic receptor agonist as an eye drop.
11 . The method of claim 10 , where the concentration of said selective α-2 agonist administered as an eye drop is between about 0.005% and about 0.050% weight by volume.
12 . The method of claim 8 , wherein said composition further comprises one or more mucoadhesive additives.
13 . The method of claim 12 , wherein said mucoadhesive additive is selected from the group consisting of carboxymethylcellulose, hydroxypropylcellulose, other cellulose derivatives, guar gum, xanthan gum, carbomers, poloxamers. chondroitin sulfate and mixtures thereof.
14 . A method of delivering an active agent for the treatment of a systemic or cerebrovascular disease or condition comprising administering to a patient in need thereof a pharmaceutical composition comprising: 1) a selective α-2 adrenergic receptor agonist having a binding affinity of 900 fold or greater for α-2 over α-1 adrenergic receptors, or a pharmaceutically acceptable salt thereof, wherein said α-2 adrenergic receptor agonist is present at a concentration from between about 0.001% to about 0.075% weight by volume; and 2) an active agent for the treatment of said systemic or cerebrovascular disease or condition.
15 . The method of claim 14 , wherein said pharmaceutical composition further comprises a mucoadhesive additive.
16 . The method of claim 15 , wherein said mucoadhesive additive is selected from the group consisting of carboxymethylcellulose, hydroxypropylcellulose, other cellulose derivatives, guar gum, xanthan gum, carbomers, poloxamers, chondroitin sulfate and mixtures thereof.
17 . The method of claim 14 , wherein said systemic or cerebrovascular disease or condition is selected from the group consisting of allergies; allergic rhinitis; disseminated intravascular coagulation; allergic shock; septic shock; gastro esophageal reflux; ear infection; sinusitis; nasal congestion; migraines; headaches; cervical dystonia; blepharospasm; spasticity; Alzheimer's disease, attention deficit disorder (ADD); depression, memory loss; sleep apnea; diabetes; asthma; transient ischemic cerebrovascular ischemic attacks (TIA's); cerebrovascular accident; degenerative cerebral disorder; pneumonia; acute respiratory distress syndrome (ARDS); acute lung injury (ALI); and infantile bronchiolitis.
18 . The method of claim 14 , wherein said active agent is selected from the group consisting of onabotulinumtoxinA, another botulinum polymer, ketorolac tromethamine, sumatriptan, dihydroergotamine, indomethacin, ibuprofen, sulindac sulfide, meclofenamic acid, flurbiprofen, hydroxycholoroquine, insulin, sulfonylureas, other oral hypoglycemics, dexmedetomidine, ketamine, prednisone, and combinations thereof.
19 . A nasal spray composition comprising brimonidine, wherein said brimonidine is at a concentration from between about 0.001% and about 0.075%.
20 . The nasal spray composition of claim 19 , wherein pH of said composition is between about 4.0 and about 7.5.
21 . The nasal spray composition of claim 19 further comprising one or more mucoadhesive additives.
22 . The nasal spray composition of claim 21 , wherein said mucoadhesive additive is selected from the group consisting of a carbomer and a poloxamer.
23 . The nasal spray composition of claim 21 , wherein said poloxamer is Poloxamer 407,
24 . The nasal spray composition of claim 23 , wherein said poloxamer is at a concentration from between about 2% and about 20%.
25 . The nasal spray composition of claim 22 , wherein said carbomer is Carbopol® 954.
26 . The nasal spray composition of claim 25 where said carbomer is at a concentration from between 0.05% and 0.5%.
27 . The nasal spray composition of claim 19 further comprising one or more ingredients selected from the group consisting of poloxamer, carbomer, hydroxypropylmethylcellulose, polyvinyl alcohol, sterile water, camphor, eucalyptol, and potassium sorbate.
28 . A method of treating a headache comprising administering to a patient in need thereof a therapeutically effective amount of the nasal spray composition of claim 19 .
29 . A method of treating atopy comprising administering to a patient in need thereof a therapeutically effective amount of the nasal spray composition of claim 19 and an allergen.
30 . A method of treating rhinitis medicamentosa comprising administering to a patient in need thereof a therapeutically effective amount of the nasal spray composition of claim 19 .
31 . A method of treating a disease or condition characterized by loss of intravascular volume due to vascular leakage comprising administering to a patient in need thereof a therapeutically effective amount of the nasal spray composition of claim 19 .
32 . The method of claim 31 , further comprising administering to said patient dexmedetomidine and/or ketamine.