Compositions, kits, apparatus, and methods for inhibiting cephalic inflammation

• US 20010004644A1
• Filed: 12/15/2000
• Published: 06/21/2001
• Est. Priority Date: 07/21/1997
• Status: Abandoned Application

• Current Assignee: Bruce H. Levin
• Original Assignee: Bruce H. Levin
• Inventors: Levin, Bruce H.
• Application Number:
  US09/737,302
• Publication Number:
  US 20010004644A1
• Time in Patent Office: Days
• US Class Current: 514/646
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• 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

Abstract

Methods, kits, apparatus, and compositions for inhibiting cephalic inflammation, including meningeal inflammation and cerebral inflammation for example, 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. A kit comprising the composition and an intranasal applicator is also included in the invention. Apparatus for delivering or applying the compositions of the invention or for performing the methods of the invention are also described.

Claims

1. A method of inhibiting cephalic inflammation in a human patient, the method comprising intranasally administering to the patient a long-acting local anesthetic pharmaceutical composition in an amount effective to inhibit the cephalic inflammation.

2. The method of

claim 1

, wherein the cephalic inflammation is associated with a cerebral neurovascular disorder.

3. The method of

claim 2

, wherein the cerebral neurovascular disorder is a neurovascular headache.

4. The method of

claim 3

, wherein the neurovascular headache is selected from the group consisting of a migraine, a cluster headache, and a headache associated with a vascular disease.

5. The method of

claim 4

, wherein the neurovascular headache is a migraine.

6. The method of

claim 2

, wherein the cerebral neurovascular disorder is an acute cerebral neurovascular disorder.

7. The method of

claim 6

, wherein the acute cerebral neurovascular disorder is selected from the group consisting of a tinnitus episode, an individual seizure, an episode of cerebrovascular spasm, an acute migraine episode, an individual headache episode associated with a cluster headache, and an individual headache associated with a vascular disease.

8. The method of

claim 7

, wherein the acute cerebral neurovascular disorder is an acute migraine episode.

9. The method of

claim 1

, wherein the long-acting local anesthetic pharmaceutical composition is dorsonasally administered to the patient.

10. The method of

claim 1

, wherein the long-acting local anesthetic pharmaceutical composition comprises at least one local anesthetic ingredient selected from the group consisting of a long-acting local anesthetic, a persistent local anesthetic, and a sustained release formulation of a local anesthetic.

11. The method of

claim 10

, wherein the local anesthetic is selected from the group consisting of ambucaine, amolanone, amylocaine, benoxinate, betoxycaine, biphenamine, bupivacaine, levo-bupivacaine, butacaine, butamben, butanilicicaine, butethamine, butoxycaine, carticaine, 2-chloroprocaine, cocaethylene, cocaine, cyclomethycaine, dibucaine, dimethisoquin, dimethocaine, diperodon, dyclonine, ecgonidine, ecgonine, ethyl aminobenzoate, ethyl chloride, levo-etidocaine, etidocaine, dextro-etidocaine, -eucaine, euprocin, fenalcomine, fomocaine, hexylcaine, hydroxyprocaine, hydroxytetracaine, isobutyl p-aminobenzoate, leucinocaine mesylate, levoxadrol, lidocaine, lidocaine salicylate monohydrate, meperidine, levo-mepivacaine, mepivacaine, meprylcaine, metabutoxycaine, methyl chloride, myrtecaine, naepaine, octacaine, orthocaine, oxethazaine, parethoxycaine, phenacaine, phenol, a pipecoloxylidide, piperocaine, piridocaine, polidocanol, pramoxine, sameridine, prilocaine, procaine, propanocaine, proparacaine, propipocaine, propoxycaine, pseudococaine, pyrrocaine, quinine urea, risocaine, ropivacaine, levo-ropivacaine, salicyl alcohol, tetracaine, tolycaine, trimecaine, veratridine, zolamine, a 2-alkyl-2-alkylamino-2′

,6′

-acetoxylidide compound, a glycerol 1,2-bis-aminoalkyl ether compound, a benzisoxazole compound, an O-aminoalkylsalicylate compound, a heterocyclic phenoxyamine compound, a 2-substituted imidazo(1,2-A) pyridine compound, a 3-aryl substituted imidazo(1,2-A) pyridine compound, a polyorganophosphazene compound, a tertiary-alkylamino-lower acyl-xylidide compound, an amidinourea compound, a 3-(5′

-adenylate) of a lincomycin compound, a 3-(5′

-adenylate) of a clindamycin compound, an N-substituted derivative of a 1-(4′

-alkylsulfonylphenyl)-2-amino-1,3-propanediol compound, a tertiary aminoalkoxyphenyl ether compound, an adenosine compound, adenosine, adenosine monophosphate, adenosine diphosphate, or adenosine triphosphate, a lauryl polyglycol ether compound, a 2-(-alkylaminoalkyl)-3-(4-substituted-benzylidene) phthalimidine compound, a 2-(-dialkylaminoalkyl)-3-(4-substituted-benzylidene) phthalimidine compound, an N,N,N-triethyl-N-alkyl ammonium salt, an L-N-n-propylpipecolic acid-2,6-xylidide compound, a polymer comprising repeating units of one or more local anesthetic moieties, an N-substituted 4-piperidinecarboxamide compound, an N-substituted 4-phenyl-4-piperidinecarboxamide compound, a compound of formula I, and a compound of formula II; and

a pharmaceutically acceptable derivative thereof.

12. The method of

claim 10

, wherein the long-acting local anesthetic pharmaceutical composition comprises at least one long-acting local anesthetic.

13. The method of

claim 12

, wherein the long-acting local anesthetic is selected from the group consisting of bupivacaine, levo-bupivacaine, ropivacaine, levo-ropivacaine, tetracaine, etidocaine, levo-etidocaine, dextro-etidocaine, levo-mepivacaine, and a pharmaceutically acceptable derivative thereof.

14. The method of

claim 12

, wherein the long-acting local anesthetic is ropivacaine.

15. The method of

claim 13

, wherein the long-acting local anesthetic is levo-ropivacaine.

16. The method of

claim 12

, wherein the long-acting local anesthetic is bupivacaine.

17. The method of

claim 15

, wherein the long-acting local anesthetic is levo-bupivacaine.

18. The method of

claim 12

, wherein the long-acting local anesthetic exists in dextro- and levo-enantiomeric forms and the long-acting local anesthetic pharmaceutical composition comprises a mixture of the dextro- and levo-enantiomers, wherein from about 5% to 30% of the long-acting local anesthetic is the dextro-enantiomer.

19. The method of

claim 10

, wherein the long-acting local anesthetic pharmaceutical composition comprises a eutectic mixture of at least one local anesthetic and a eutectic ingredient.

20. The method of

claim 10

, wherein the long-acting local anesthetic is present in the composition at a concentration of about 0.01% to about 53% by weight.

21. The method of

claim 10

, wherein the long-acting local anesthetic is administered to the patient at a dose in an amount of about 10 micrograms to about 2.5 grams.

22. The method of

claim 10

, wherein the long-acting local anesthetic pharmaceutical composition is administered in a unit dosage form comprising an amount of the local anesthetic of about 10 micrograms to about 2.5 grams.

23. The method of

claim 10

, wherein the long-acting pharmaceutical composition further comprises a pharmaceutically acceptable carrier selected from the group consisting of jelly, creme, gel, semi-solid, liquid, droplet, aerosol, powder, microsome, liposome, emulsion, sol-gel, foam, sustained release, degradable polymer, impregnated film, impregnated fiber, impregnated patch, coated film, coated fiber, coated patch, flexible solid, semisolid carrier, polymeric matrix, suspended microspheres, and thermoreversible gel.

24. The method of

claim 10

, wherein the composition is in a form selected from the group consisting of jelly, creme, gel, semi-solid, emulsion, sol-gel, foam, eutectic mixture, thermoreversible gel, and fluid which exhibits an increase in viscosity in a human nasal cavity.

25. The method of

claim 10

, wherein the composition further comprises a pharmaceutically effective amount of a pharmaceutically active agent selected from the group consisting of a vasoconstrictor, epinephrine, norepinephrine, phenylephrine, methysergide, propanolol, a calcium channel blocker, verapamil, ergot, an ergotamine preparation, dihydroergotamine, a serotonin agonist, sumatriptan, zolmitriptan, rizatriptan, naratriptan, a chroman compound, aspirin, acetaminophen, a non-steroidal anti-inflammatory drug, caffeine, a narcotic, butorphanol tartrate, meperidine, a mast cell degranulation inhibitor, cromolyn sodium, eucalyptol, tetrodotoxin, desoxytetrodotoxin, saxitoxin, an organic acid, a sulfite salt, an acid salt, a glucocorticoid compound, a steroid ester, magnesium or lithium ions, a centrally-acting analgesic, a beta blocker, an agent that increases cerebral levels of -aminobutyric acid, butalbital, a drug that increases cerebral levels of -aminobutyric acid, a benzodiazepine, valproat, gabapentin, divalproex sodium, a tri-cyclic antidepressant, a narcotic analgesic, an oral muscle relaxant, a tranquilizer, and a muscle relaxant.

27. The method of

claim 25

, wherein the effective period is at least about one hour.

28. The method of

claim 25

, wherein the effective period is at least about two hours.

29. The method of

claim 25

, wherein anesthetizing the nerve structure comprises a method selected from the group consisting of performing acupuncture upon the nerve structure, applying an electrical potential to the nerve structure, applying electromagnetic radiation to the nerve structure, and administering a long-acting local anesthetic pharmaceutical composition to the nerve structure.

30. The method of

claim 28

, wherein the nerve structure is a dorsonasal nerve structure and wherein the dorsonasal nerve structure is anesthetized by dorsonasally administering to the patient a long-acting local anesthetic pharmaceutical composition.

31. The method of

claim 25

, wherein the cephalic inflammation is associated with migraine.

26. A method of inhibiting cephalic inflammation in a human patient, the method comprising anesthetizing a nerve structure associated with the disorder in the patient for a period effective to inhibit the inflammation.

32. A method of inhibiting cephalic inflammation in a human patient, the method comprising energizing a dorsonasally implanted electronic neural stimulator.