Method for directed intranasal administration of a composition

• US 7,799,337 B2
• Filed: 08/12/2002
• Issued: 09/21/2010
• Est. Priority Date: 07/21/1997
• Status: Expired due to Fees

• Current Assignee: BHL Patent Holdings LLC
• Original Assignee: Bruce H. Levin
• Inventors: Levin, Bruce H.
• Primary Examiner(s): HUI, SAN MING R
• Application Number:
  US10/218,138
• Publication Number:
  US 20030133877A1
• Time in Patent Office: 2,962 Days
• Field of Search: 424/434, 424/401, 600/120, 600/144
• US Class Current: 424/434
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/245 Amino benzoic acid types, e.g. procaine, novocaine salicylic acid esters A61K31/60
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/618 having the carboxyl group in position 1 esterified, e.g. salsalate
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61M 15/08 Inhaling devices inserted into the nose
• CPC Class Codes: A61M 2205/075 Bulb type
• CPC Class Codes: A61M 2210/0618 Nose
• CPC Class Codes: A61M 2230/005 Parameter used as control input for the apparatus
• CPC Class Codes: A61M 31/00 Devices for introducing or retaining media, e.g. remedies, in cavities of the body A61M25/00 takes precedence ; introducing or retaining ophthalmic products into the ocular cavities A61F9/0008
• CPC Class Codes: A61N 1/0546 Nasal electrodes
• CPC Class Codes: A61N 1/0551 Spinal or peripheral nerve electrodes
• CPC Class Codes: A61N 1/36075 Headache or migraine
• CPC Class Codes: A61N 5/00 Radiation therapy ultrasound therapy A61N7/00; devices or apparatus applicable to both therapy and diagnosis A61B6/00

Abstract

Methods, kits, apparatus, and compositions for inhibiting a cerebral neurovascular disorder, a muscular headache, or cerebral inflammation in a human patient are provided. The methods comprise intranasally administering to the patient a pharmaceutical composition comprising a local anesthetic, and preferably a long-acting local anesthetic ingredient. A composition useful for practicing the methods of the invention is described which comprises at least one local anesthetic in a pharmaceutically acceptable carrier, wherein the composition is formulated for intranasal delivery. Cerebral neurovascular disorders include migraine and cluster headache. Muscular headaches include tension headaches and muscle contraction headaches. A kit comprising the composition and an intranasal applicator and a method of systemically delivering a pharmaceutically active agent to an animal are also included in the invention. Apparatus for directed intranasal administration of the compositions of the invention and for performing the methods of the invention are also described.

Claims

1. A method of intranasally administering a composition directly to a selected intranasal location of a human patient other than for effecting a block of the sphenopalatine ganglion, the method comprising

providing a composition comprising a pharmaceutically active agent which is a pharmaceutically active agent other than a local anesthetic or which is a pharmaceutically active agent in combination with a local anesthetic, wherein the composition does not have only a local anesthetic as the only pharmaceutically active agent,

inserting into a nostril of the patient an intranasal delivery device comprising a preformed body having a proximal end and a distal portion having a distal end, wherein the distal portion of the delivery device is curved or angled with respect to a longitudinal axis of the body, the longitudinal axis of the body at the distal end forming an angle of about 90 degrees to about 170 degrees with respect to the longitudinal axis at the proximal end prior to insertion of the distal end into a nasal cavity,

urging the delivery device through the nostril such that the distal end is directed to the selected intranasal location, and

directing the administration of the composition directly to the selected intranasal location via the delivery device by one of

contacting the selected intranasal location by the composition on at least a portion of the distal end of the delivery device and

by delivering the composition through at least one outlet port at the distal portion of the delivery device to which the composition is delivered through a lumen extending through the body to the selected intranasal location for causing the composition to selectively enter at least one of (i) the inferior boundary of the nasopharynx, (ii) sinuses via pathways specific thereto, and (iii) cerebral tissue selected from the group consisting of cerebral spinal fluid, a cerebral neuronal structure and cerebral vasculature, via pathways specific thereto.

2. The method of claim 1, wherein the delivery device has a shape which conforms to the shape of a human nasal cavity.

3. The method of claim 1, wherein the composition is present on at least a portion of the exterior surface of the body at the distal portion thereof and the method further comprises contacting the selected intranasal location with the composition on at least the portion of the exterior surface.

4. The method of claim 1, wherein the device includes at least one outlet port adapted to face the selected intranasal location and a lumen extending in the body from the proximal end thereof to the outlet port, the method further comprising providing the composition to the selected intranasal location through the outlet port by way of the lumen.

5. The method of claim 4, wherein the composition is provided to the lumen from a reservoir remote from the distal portion of the delivery device.

6. The method of claim 4, the method further comprising

urging the device through the nostril such that the distal portion of the body is in a human nasal cavity and the outlet port faces the selected intranasal location, and

urging an elongate instrument through the lumen, wherein the elongate instrument is selected from the group consisting of an extendable instrument comprising the composition, a swab impregnated with the composition, a rosette impregnated with the composition, a needle coated with the composition, an inflatable instrument comprising the composition, a balloon coated with the composition, a balloon impregnated with the composition, a hollow instrument having a lumen for providing the composition, and a hollow needle having a needle lumen for providing the composition, whereby the composition is provided to the selected intranasal location.

7. The method of claim 1, wherein the selected intranasal location is one of a superior portion and a posterior portion of a nasal cavity.

8. The method of claim 1, wherein the method further comprises directing the composition directly to a selected intranasal location that overlies a structure selected from the group consisting of an intranasal nerve structure and an intranasal blood vessel.

9. The method of claim 8, wherein the intranasal nerve structure is selected from the group consisting of a trigeminal nerve, vidian nerve, olfactory nerve, nasal nerve, ethmoidal nerve, palatine nerve, greater petrosal nerve, ciliary nerve and maxillary nerve.

10. The method of claim 1, wherein the composition comprises a local anesthetic with another pharmaceutically active agent.

11. The method of claim 10, wherein the local anesthetic is selected from the group consisting of a long-acting local anesthetic, a persistent local anesthetic, and a sustained release formulation of a local anesthetic.

12. The method of claim 1, wherein the composition comprises an ingredient selected from the group consisting of a stem cell, DNA, RNA, oligonucleotide, polypeptide, amino acid, fatty acid, lipid, carbohydrate, vitamin, mineral, nutrient, antibiotic, antiviral agent, antifungal agent, neurotransmitter, antiepileptic agent, antiseizure agent, analgesic, anti-neuropathic pain agent, anti-central pain agent, antidepressant agent, cox inhibitor, LOX inhibitor, growth factor, hormone, ATP, ADP, NAD(P), NAD(P)H, propylene glycol, carrier molecule, DMSO, cytokine, anti-cytokine, TNF, anti-inflammatory agent, melatonin, chemotherapy agent, radiolabeled compound, carrier virus, therapeutic microorganism, aspirin, acetaminophen, a non-steroidal anti-inflammatory drug, a tricyclic antidepressant, an anxiolytic, a serotonin agonist, a narcotic, vasoconstrictor, epinephrine, norepinephrine, phenylephrine, methysergide, propanolol, a calcium channel blocker, verapamil, ergot, an ergotamine preparation, dihydroergotamine, sumatriptan, zolmitriptan, rizatriptan, naratriptan, caffeine, butorphanol tartrate, meperidine cromolyn sodium, eucalyptol, tetrodotoxin, desoxytetrodotoxin, saxitoxin, magnesium ion, lithium ion, a centrally-acting analgesic, a beta blocker, (S)-alpha-phenyl-2-pyridineethanamine (S)-malate, butalbital, a benzodiazepine, valproat, gabapentin, divalproex sodium, a tranquilizer, a muscle relaxant and an anti-emetic.

13. The method of claim 1, wherein the composition comprises a compound selected from the group consisting of an anti-epileptic, phenytoin sodium, a serotonin receptor agonist, a serotonin subclass 5HT1F receptor agonist, LY334,370, a sesquiterpene lactone, parthanolide, Tanacetum parthenium, and an extract of Tanacetum parthenium.

14. The method of claim 1, wherein the composition is delivered in a form selected from the group consisting of a liquid, a gel, a creme, a foam, a mousse, a powder, a dispersed powder, an atomized liquid, an aerosol, microparticles, an emulsion, a eutectic mixture, a thermoreversible gel and a liposomal preparation.

15. A method of intranasally administering a composition directly to a selected intranasal location of a human patient other than for effecting a block of the sphenopalatine ganglion, the method comprising

(a) providing a composition comprising a pharmaceutically active agent which is a pharmaceutically active agent other than a local anesthetic or which is a pharmaceutically active agent in combination with a local anesthetic, wherein the composition does not have only a local anesthetic as the only pharmaceutically active agent,

(b) seating within the nasal cavity of the patient an anatomically adapted intranasal delivery nozzle, the nozzle comprising a preformed body having

a delivery lumen extending therethrough from a proximal end of the body to an outlet port at a distal portion of the body, and

an exterior portion having

(i) a flattened portion extending situated peripherally between the proximal end and the distal portion and extending substantially from the proximal end to the distal portion, for seating the nozzle against the nasal septum of the patient,

(ii) an anterior portion situated peripherally between the proximal end and the distal portion for seating the nozzle against a portion of the nasal cartilage of the patient, and

(iii) an indented portion situated peripherally between the proximal end and the distal portion for seating the nozzle against a nasal concha of the patient, wherein when the nozzle is seated, the outlet port is situated within the nasal cavity of the patient such that the axis extending through the discharge port is offset from the apex of the nasal cavity by no more than about 30 degrees, and thereafter

(c) providing the composition to the delivery lumen, whereby the composition is intranasally administered in a directed manner to the selected intranasal location for causing the composition to selectively enter at least one of (i) the inferior boundary of the nasopharynx, (ii) sinuses via pathways specific thereto, and (iii) cerebral tissue selected from the group consisting of cerebral spinal fluid, a cerebral neuronal structure and cerebral vasculature, via pathways specific thereto.

16. The method of claim 15, wherein the composition is provided to the delivery lumen from a reservoir remote from the distal portion of the delivery device.

17. The method of claim 15, wherein the method further comprises directing the composition directly to a selected intranasal location that is a portion of nasal epithelium overlying a structure selected from the group consisting of an intranasal nerve structure and an intranasal blood vessel.

18. The method of claim 17, wherein the intranasal nerve structure is selected from the group consisting of a trigeminal nerve, vidian nerve, olfactory nerve, nasal nerve, ethmoidal nerve, palatine nerve, greater petrosal nerve, ciliary nerve and maxillary nerve.

19. The method of claim 15, wherein the composition comprises a local anesthetic with another pharmaceutically active agent.

20. The method of claim 19, wherein the local anesthetic is selected from the group consisting of a long-acting local anesthetic, a persistent local anesthetic, and a sustained release formulation of a local anesthetic.

21. The method of claim 15, wherein the composition comprises an ingredient selected from the group consisting of a stem cell, DNA, RNA, oligonucleotide, polypeptide, amino acid, fatty acid, lipid, carbohydrate, vitamin, mineral, nutrient, antibiotic, antiviral agent, antifungal agent, neurotransmitter, antiepileptic agent, antiseizure agent, analgesic, anti-neuropathic pain agent, anti-central pain agent, antidepressant agent, cox inhibitor, LOX inhibitor, growth factor, hormone, ATP, ADP, NAD(P), NAD(P)H, propylene glycol, carrier molecule, DMSO, cytokine, anti-cytokine, TNF, anti-inflammatory agent, melatonin, chemotherapy agent, radiolabeled compound, carrier virus, therapeutic microorganism, aspirin, acetaminophen, a non-steroidal anti-inflammatory drug, a tricyclic antidepressant, an anxiolytic, a serotonin agonist, a narcotic, vasoconstrictor, epinephrine, norepinephrine, phenylephrine, methysergide, propanolol, a calcium channel blocker, verapamil, ergot, an ergotamine preparation, dihydroergotamine, sumatriptan, zolmitriptan, rizatriptan, naratriptan, caffeine, butorphanol tartrate, meperidine, cromolyn sodium, eucalyptol, tetrodotoxin, desoxytetrodotoxin, saxitoxin, magnesium ion, lithium ion, a centrally-acting analgesic, a beta blocker, (S)-alpha-phenyl-2-pyridineethanamine (S)-malate, butalbital, a benzodiazepine, valproat, gabapentin, divalproex sodium, a tranquilizer, a muscle relaxant and an anti-emetic.

22. The method of claim 15, wherein the composition comprises a compound selected from the group consisting of an anti-epileptic, phenytoin sodium, a serotonin receptor agonist, a serotonin subclass 5HT1F receptor agonist, LY334,370, a sesquiterpene lactone, parthanolide, Tanacetum parthenium, and an extract of Tanacetum parthenium.

23. The method of claim 15, wherein the composition is delivered in a form selected from the group consisting of a liquid, a gel, a creme, a foam, a mousse, a powder, a dispersed powder, an atomized liquid, an aerosol, microparticles, an emulsion, a eutectic mixture, a thermoreversible gel and a liposomal preparation.