Non-invasive ocular drug delivery

Abstract

The present invention is drawn to a pharmaceutical compound for the treatment of posterior retinal diseases through topical application of the compound. The compound includes an effective amount of a therapeutic compound, and at least one additional agent that helps to prolong the residence time of the therapeutic compound within the extraocular space, or increase the transport of the therapeutic compound across a tissue of an eye toward and into a posterior ocular region, or both. The invention is additionally drawn to a device and method for delivering the compound.

1 - 100 . (canceled) 
     
     
         101 . An ophthalmic device for the topical delivery of a therapeutic compound into an eye, comprising:
 a fluid retaining member;   a therapeutic compound for treating posterior retinal conditions releasably associated with the fluid retaining member;   a structure for enhancing the transport of the therapeutic compound across the sclera of an eye toward and into at least one of an intermediate and a posterior portion of the eye; and   at least one prolonging agent for prolonging the residence time of the therapeutic compound within the portion of the eye.   
     
     
         102 . The device of  claim 101 , further comprising a transport agent for enhancing the transport of the therapeutic compound across the sclera of an eye toward and into at least one of an intermediate and a posterior portion of the eye. 
     
     
         103 . The device of  claim 102 , wherein the transport agent is an α-agonist vasoconstrictor. 
     
     
         104 . The device of  claim 103 , wherein the α-agonist vasoconstrictor is selected from one of the group consisting of naphazoline, tetrahydrozoline, and sympathomimetics. 
     
     
         105 . The device of  claim 103 , wherein the α-agonist vasoconstrictor includes a sympathomimetic amine selected from one of the group consisting of phenylethylamine, epinephrine, norepinephrine, dopamine, dobutamine, colterol, ethylnorepinephrine, isoproterenol, isoetharine, metaproterenol, terbutaline, metaraminol, phenylephrine, tyramine, hydroxyamphetamine, ritrodrine, prenalterol, methoxamine, albuterol, amphetamine, methamphetamine, benzphetamine, ephedrine, phenylpropanolamine, methentermine, phentermine, fenfluramine, propylhexedrine, diethylpropion, phenmetrazine, and phendimetrazine. 
     
     
         106 . The device of  claim 102 , wherein the transport agent is an encapsulating agent that encapsulates the therapeutic compound. 
     
     
         107 . The device of  claim 106 , wherein the encapsulating agent includes a member selected from the group consisting of liposomes, micelles, microemulsions, nanoparticles, and cyclodextrins. 
     
     
         108 . The device of  claim 101 , wherein the structure for enhancing transport is a seal surrounding the fluid retaining member operable to form a fluid-tight seal on the eye to preclude entry of lachrymal fluid into the drug transport space. 
     
     
         109 . The device of  claim 101 , wherein the prolonging agent is an α-agonist vasoconstrictor. 
     
     
         110 . The device of  claim 109 , wherein the α-agonist vasoconstrictor is selected from one of the group consisting of naphazoline, tetrahydrozoline, and sympathomimetics. 
     
     
         111 . The device of  claim 109 , wherein the α-agonist vasoconstrictor includes a sympathomimetic amine selected from one of the group consisting of phenylethylamine, epinephrine, norepinephrine, dopamine, dobutamine, colterol, ethylnorepinephrine, isoproterenol, isoetharine, metaproterenol, terbutaline, metaraminol, phenylephrine, tyramine, hydroxyamphetamine, ritrodrine, prenalterol, methoxamine, albuterol, amphetamine, methamphetamine, benzphetamine, ephedrine, phenylpropanolamine, methentermine, phentermine, fenfluramine, propylhexedrine, diethylpropion, phenmetrazine, and phendimetrazine. 
     
     
         112 . The device of  claim 101 , wherein the prolonging agent is an encapsulating agent that encapsulates the therapeutic compound. 
     
     
         113 . The device of  claim 112 , wherein the encapsulating agent includes a member selected from the group consisting of liposomes, micelles, microemulsions, nanoparticles, and cyclodextrins. 
     
     
         114 . The device of  claim 101 , wherein the therapeutic compound includes a member selected from the group consisting of steroids, antibacterials, antivirals, antifungals, antimetabolites, VEGF inhibitors, ICAM inhibitors, antibodies, protein kinase C inhibitors, chemotherapeutic agents, neuroprotective agents, nucleic acid derivatives, aptamers, proteins, enzymes, peptides, polypeptides, immunosuppressive agents, mast cell stabilizing agents, and mycophenolate mofetil. 
     
     
         115 . The device of  claim 101 , further comprising a rate-limiting membrane associated with the fluid retaining member and operable to control the rate of delivery of the therapeutic agent from the fluid retaining member. 
     
     
         116 . The device of  claim 101 , further comprising an active driving force operable to decrease the lag-time of molecular transport. 
     
     
         117 . The device of  claim 116 , wherein the active driving force includes a member selected from the group consisting of ultra sound and iontophoresis. 
     
     
         118 . A pharmaceutical formulation for the treatment of an ocular condition, comprising:
 an effective amount of a therapeutic compound;   an encapsulating agent encapsulating at least a portion of the therapeutic compound; and   α-agonist vasoconstrictor, the encapsulating agent and the α-agonist vasoconstrictor being operable to enhance transport of the therapeutic compound across the sclera of an eye toward and into at least one of an intermediate and a posterior portion of the eye, and to prolong residence time of the therapeutic compound within the portion of the eye.   
     
     
         119 . The formulation of  claim 118 , wherein the α-agonist vasoconstrictor is selected from one of the group consisting of naphazoline, tetrahydrozoline, and sympathomimetics. 
     
     
         120 . The formulation of  claim 118 , wherein the α-agonist vasoconstrictor includes a sympathomimetic amine selected from one of the group consisting of phenylethylamine, epinephrine, norepinephrine, dopamine, dobutamine, colterol, ethylnorepinephrine, isoproterenol, isoetharine, metaproterenol, terbutaline, metaraminol, phenylephrine, tyramine, hydroxyamphetamine, ritrodrine, prenalterol, methoxamine, albuterol, amphetamine, methamphetamine, benzphetamine, ephedrine, phenylpropanolamine, methentermine, phentermine, fenfluramine, propylhexedrine, diethylpropion, phenmetrazine, and phendimetrazine. 
     
     
         121 . The formulation of  claim 118 , wherein the encapsulating agent includes a member selected from the group consisting of liposomes, micelles, microemulsions, nanoparticles, and cyclodextrins. 
     
     
         122 . The formulation of  claim 118 , wherein the therapeutic compound includes a member selected from the group consisting of steroids, antibacterials, antivirals, antifungals, antimetabolites, VEGF inhibitors, ICAM inhibitors, antibodies, protein kinase C inhibitors, chemotherapeutic agents, neuroprotective agents, nucleic acid derivatives, aptamers, proteins, enzymes, peptides, polypeptides, immunosuppressive agents, mast cell stabilizing agents, and mycophenolate mofetil. 
     
     
         123 . A method for increasing the concentration of a therapeutic compound in an intermediate or a posterior region of a patient's eye, comprising:
 administering an effective amount of a therapeutic compound to the eye;   minimizing pre-retinal clearance of the therapeutic compound from the eye; and   administering an α-agonist vasoconstrictor to the eye to prolong residence time of the therapeutic compound in an intermediate or posterior portion of the eye.   
     
     
         124 . The method of  claim 123 , wherein the α-agonist vasoconstrictor is selected from one of the group consisting of naphazoline, tetrahydrozoline, and sympathomimetics. 
     
     
         125 . The method of  claim 123 , wherein the α-agonist vasoconstrictor includes a sympathomimetic amine selected from one of the group consisting of phenylethylamine, epinephrine, norepinephrine, dopamine, dobutamine, colterol, ethylnorepinephrine, isoproterenol, isoetharine, metaproterenol, terbutaline, metaraminol, phenylephrine, tyramine, hydroxyamphetamine, ritrodrine, prenalterol, methoxamine, albuterol, amphetamine, methamphetamine, benzphetamine, ephedrine, phenylpropanolamine, methentermine, phentermine, fenfluramine, propylhexedrine, diethylpropion, phenmetrazine, and phendimetrazine. 
     
     
         126 . The method of  claim 123 , wherein minimizing pre-retinal clearance of the therapeutic compound from the eye includes inhibiting access of lachrymal fluid to the therapeutic compound. 
     
     
         127 . The method of  claim 126 , wherein inhibiting access of lachrymal fluid to the therapeutic compound includes forming a fluid-tight seal on a surface of the eye surrounding the therapeutic compound. 
     
     
         128 . The method of  claim 123 , further comprising encapsulating the therapeutic compound with an encapsulating agent to increase transport of the therapeutic compound across the sclera and to prolong residence time of the therapeutic compound within the portion of the eye. 
     
     
         129 . The method of  claim 128 , wherein the encapsulating agent includes a member selected from the group consisting of liposomes, micelles, microemulsions, and combinations thereof. 
     
     
         130 . The method of  claim 128 , wherein the encapsulating agent decreases degradation of the therapeutic compound by encapsulating the therapeutic compound thereby inhibiting metabolism by lachrymal enzymes. 
     
     
         131 . The method of  claim 123 , wherein the therapeutic compound includes a member selected from the group consisting of steroids, antibacterials, antivirals, antifungals, antimetabolites, VEGF inhibitors, ICAM inhibitors, antibodies, protein kinase C inhibitors, chemotherapeutic agents, neuroprotective agents, nucleic acid derivatives, aptamers, proteins, enzymes, peptides, polypeptides, immunosuppressive agents, mast cell stabilizing agents, mycophenolate mofetil, and combinations thereof. 
     
     
         132 . The method of  claim 123 , further comprising delivering the therapeutic compound to the eye with an active driving force. 
     
     
         133 . The method of  claim 132 , wherein the active driving force includes a member selected from the group consisting of ultra sound and iontophoresis.