Therapy procedure for drug delivery for trigeminal pain

Abstract

The present invention relates to methods for the treatment or prevention of trigeminal nerve-associated pain, in particular chronic, acute and procedural-related pain. The methods comprise administration of analgesic agents to the trigeminal nerve system which results in analgesia to the facial or head region.

1 . A method for treating an individual for trigeminal nerve-associated pain, comprising: administering to the individual an effective amount of an analgesic agent wherein the administration is targeted to the trigeminal nerve system and results predominantly in analgesia to the facial or head region as compared to analgesic effects in other parts of the body.  
     
     
         2 . A method according to  claim 1 , wherein the administration results in minimal CNS or systemic side effects.  
     
     
         3 . A method according to  claim 1 , wherein the administration results in reduction of a pain rating on the VAS of 30% or more.  
     
     
         4 . A method according to  claim 1 , wherein the analgesic agent is administered via mucosal administration, wherein mucosal administration comprises intranasal administration, buccal administration, sublingual administration and conjunctival administration.  
     
     
         5 . A method according to  claim 1 , wherein the analgesic agent is administered via transdermal administration, wherein transdermal administration comprises administering the agent to the skin of the face, forehead, eyelids, nose, cheek, chin, scalp, temple region or a combination thereof.  
     
     
         6 . A method according to  claim 1 , wherein the analgesic agent is administered via intranasal administration.  
     
     
         7 . A method according to  claim 1 , wherein the analgesic agent is administered via buccal or sublingual administration.  
     
     
         8 . A method according to  claim 1 , wherein the analgesic agent is administered via conjunctival administration or via other tissues around the eye.  
     
     
         9 . A method according to  claim 1 , wherein the analgesic agent comprises a peptide.  
     
     
         10 . A method according to  claim 9 , wherein the peptide is administered in combination with at least one additional agent.  
     
     
         11 . A method according to  claim 9 , wherein the peptide is selected from the group comprising enkephalins, endorphins, dynorphins, endomorphins, casomorphins, dermorphin, oxytocin, octreotide, and analogues and derivatives thereof.  
     
     
         12 . A method according to  claim 1 , wherein the analgesic agent comprises an agent selected from the group comprising peptidergic channel modulators, peptidergic enzyme inhibitors, analgesic enzymes, trophic factors, peptidergic receptor agonists, peptidergic receptor antagonists, amino acid receptor agonists, N-methyl-D-aspartate receptor blockers, NSAIDs, steroid anti-inflammatory drugs, ion channel blockers, antidepressants, anti-seizure medications, nicotinic agonists, opioids, antibodies directed toward proalgesic antigens and antibodies directed to other neuropeptides.  
     
     
         13 . A method according to  claim 12 , comprising administering at least two analgesic agents.  
     
     
         14 . A method according to  claim 1 , wherein the trigeminal nerve-associated pain is selected from the group consisting of chronic, acute and procedural-related pain and combinations thereof.  
     
     
         15 . A method according to  claim 14 , wherein the chronic pain is selected from the group consisting of trigeminal neuralgia, atypical facial pain, anesthesia dolorosa, post-herpetic neuralgia, cancer of the head and neck, migraine headaches, and temporomandibular joint pain.  
     
     
         16 . A method according to  claim 14 , wherein the procedural-related pain is pain arising from dental, medical, surgical or cosmetic procedures.  
     
     
         17 . A method according to  claim 14 , wherein the acute pain is pain arising from a laceration, a bum, a broken bone, a headache, a dental disease, a bacterial infection, an abscessed tooth, or a sinus infection.  
     
     
         18 . A method according to  claim 1 , wherein the analgesic agent is administered as a pharmaceutical composition.  
     
     
         19 . A method according to  claim 18 , wherein the pharmaceutical composition is administered as a powder, a gel, an ointment, a liquid, a suspension, a cream or a bioadhesive.  
     
     
         20 . A method according to  claim 18 , wherein the pharmaceutical composition further comprises at least one protease inhibitor or at least one absorption enhancer.  
     
     
         21 . A method according to  claim 18 , wherein the pharmaceutical composition further comprises at least one protease inhibitor and at least one absorption enhancer.  
     
     
         22 . A method according to  claim 1 , wherein the method further comprises administration of a vasoconstrictor.  
     
     
         23 . A method according to  claim 22 , wherein the vasoconstrictor is administered prior to the analgesic agent.  
     
     
         24 . A method according to  claim 22 , wherein the vasoconstrictor is co-administered with the analgesic agent.  
     
     
         25 . A method according to  claim 22 , wherein administration of the vasoconstrictor reduces systemic distribution of the analgesic agent.  
     
     
         26 . A method according to  claim 25 , wherein reduced systemic distribution allows for a decreased effective dosage of the analgesic agent to achieve analgesia.  
     
     
         27 . A method according to  claim 1 , wherein the method further comprises administration of at least one protease inhibitor and at least one absorption enhancer.  
     
     
         28 . A method according to  claim 1 , wherein the method further comprises administration of at least one protease inhibitor, at least one absorption enhancer and a vasoconstrictor.  
     
     
         29 . A method according to  claim 20 , wherein the protease inhibitor is selected from a group comprising antipain, arphamenine A and B, benzamidine HCl, AEBSF, CA-074, calpain inhibitor I and II, calpeptin, pepstatin A, actinonin, amastatin, bestatin, chloroacetyl-HOLeu-Ala-Gly-NH 2 , DAPT, diprotin A and B, ebelactone A and B, foroxymithine, leupeptin, pepstatin A, phosphoramidon, aprotinin, BBI, soybean trypsin inhibitor, phenylmethylsulfonyl fluoride, E-64, chymostatin, 1,10-phenanthroline, EDTA and EGTA.  
     
     
         30 . A method according to  claim 20 , wherein the absorption enhancer is selected from a group comprising surfactants, bile salts, bioadhesive agents, phospholipid additives, mixed micelles, liposomes, or carriers, alcohols, enamines, cationic polymers, NO donor compounds, long-chain amphipathic molecules, small hydrophobic penetration enhancers; sodium or a salicylic acid derivatives, glycerol esters of acetoacetic acid, cyclodextrin or beta-cyclodextrin derivatives, medium-chain fatty acids, chelating agents, amino acids or salts thereof, N-acetylamino acids or salts thereof, mucolytic agents, enzymes specifically targeted to a selected membrane component, inhibitors of fatty acid synthesis and inhibitors of cholesterol synthesis.  
     
     
         31 . A method according to  claim 22 , wherein the vasoconstrictor is selected from a group comprising phenylephrine hydrochloride, tetrahydrozoline hydrochloride, naphazoline nitrate, oxymetazoline hydrochloride, tramazoline hydrochloride, endothelin-1, endothelin-2, epinephrine, norepinephrine and angiotensin.  
     
     
         32 . A method for treating an individual for trigeminal nerve-associated pain, comprising: administering to an individual an effective amount of an analgesic agent wherein the agent is administered by transmucosal or transdermal administration and results predominantly in analgesia to the facial or head region as compared to analgesic effects in other parts of the body.  
     
     
         33 . A method for treating an individual for trigeminal nerve-associated pain, comprising: administering to an individual an effective amount of an analgesic agent wherein the administration is targeted to the trigeminal nerve system and results predominantly in localized analgesia to the facial or head region with minimal central nervous system effects or systemic side effects.  
     
     
         34 . A method for treating an individual for trigeminal nerve-associated pain, comprising: administering to an individual an effective amount of an analgesic agent to the nasal cavity of the individual wherein the administration is targeted to the trigeminal nerve system and results predominantly in analgesia localized to the facial or head region as compared to analgesic effects in other parts of the body.  
     
     
         35 . A method according to  claim 34 , further comprising the administration of a vasoconstrictor.  
     
     
         36 . A method according to  claim 34 , wherein the administration is directed to the inferior two-thirds of the nasal cavity.  
     
     
         37 . A method according to  claim 34 , wherein the administration is directed to the inferior two-thirds of the nasal cavity and away from the olfactory region.  
     
     
         38 . A kit comprising at least one analgesic agent, suitable packaging and instructions for treatment of trigeminal nerve-associated pain.  
     
     
         39 . A kit according to  claim 36 , further comprising a delivery device.  
     
     
         40 . A kit according to  claim 36 , further comprising a vasoconstrictor.