Method and system for effecting changes in pigmented tissue

Abstract

Methods and systems are described for a rapid and sustainable change in the pigment melanin content of melanocytes of the iris stroma, thereby to change the color of the eye. Also described are nanoparticle compositions for lightening or darkening the pigmented tissues or treating a pigmented tissue disease.

What is claimed is: 
     
         1 . A method of lightening the color of the iris of a human subject, the method comprising administering to the iris of the human subject an amount of a composition comprising a tyrosinase inhibitor effective to lighten the color of the iris of the human subject. 
     
     
         2 . The method of  claim 1 , wherein the tyrosinase inhibitor is hydroquinone, 
     
     
         3 . The method of  claim 1 , wherein the tyrosinase inhibitor is oxyresveratrol or tetrahydroxyisoflavone. 
     
     
         4 . The method of any one of  claims 1 - 3 , wherein the composition further comprises at least one melanogenesis inhibitor. 
     
     
         5 . The method of  claim 4 , wherein the melanogenesis inhibitor is selected from the group consisting of glutamate receptor blocker, an alpha-adrenergic blocker, a matrix metalloproteinases inhibitor, a Cox inhibitor. a cholinergic agonist, a downregulator of mitf, tyr &Trp1, an acidifier of melanosomes, an opioid receptor antagonist, a Pmel 17 blocker, and a fibroblast growth factor inhibitor. 
     
     
         6 . The method of  claim 5 , wherein the glutamate receptor blocker is memantine, the alpha-adrenergic blocker is thymoxamine, the matrix metalloproteinases inhibitor is prinomastat, the Cox inhibitor is bromfenac, the cholinergic agonist is pilocarpine, the downregulator of mitf, tyr &Trp1 is Haginin A or 4,4 1 -dihyldroxybiphenyl, the acidifier of melanosomes is H89, the opioid receptor antagonist is naloxone, and the Pmel 17 blocker is calmodulin inhibitors, and with Transforming Growth Factor (TGF) family. 
     
     
         7 . The method of any one of  claims 4 - 6 , wherein the composition comprises hydroquinone, memantine and Haginin A. 
     
     
         8 . The method of any one of  claims 4 - 6 , wherein the composition comprises oxyresveratrol, 4,4′-dihyldroxybiphenyl and H89. 
     
     
         9 . The method of any one of  claims 4 - 6 , wherein the composition comprises tetrahydroxyisoflavone, prinomastat and naloxone. 
     
     
         10 . The method of any one of  claims 1 - 9 , wherein the composition is administered in conjunction with an injection of saline, siRNA, botulinum toxin, or a combination of botulinum toxin and siRNA. 
     
     
         11 . The method of any one of  claims 1 - 10 , wherein the composition is administered through a nanoparticle drug delivery system containing a targeting agent of iridial melanocytes. 
     
     
         12 . The method of  claim 11 , wherein the targeting agent comprises a composition of iron, zinc, gold, or a combination thereof. 
     
     
         13 . The method of  claim 12 , wherein the targeting agent comprises zinc oxide. 
     
     
         14 . The method of any one of  claims 1 - 13 , wherein the composition is in the form of eye drops. 
     
     
         15 . The method of any one of  claims 1 - 13 , wherein the composition is administered through an ophthalmic drug delivery system selecting from the group consisting of salves, creams, emulsions and gels. 
     
     
         16 . The method of  claim 14  or  15 . wherein the composition is administered in the fornices under the eyelid. 
     
     
         17 . The method of any one of  claims 1 - 13 , wherein the composition is administered through an ophthalmic drug delivery system comprising a time-release coated insert. 
     
     
         18 . The method of  claim 17 , wherein the time-release coated insert is coated on at least one side. 
     
     
         19 . The method of any one of  claims 1 - 18 , wherein the subject is a healthy human. 
     
     
         20 . The method of any one of  claims 1 - 18 , wherein the subject is afflicted with glaucoma. 
     
     
         21 . A method of introducing pigments to the iris of a human subject, comprising administering to the iris an amount of at least one melanogenesis promoter, effective to introduce pigments to the iris of the human subject. 
     
     
         22 . The method of  claim 21 , wherein the iris of the human subject darkens after the introduction of pigments to the iris. 
     
     
         23 . The method of  claim 22 , wherein the at least one melanogenesis promoter is prostaglandin, forskolin, 1-oleoyl-2-acetylglycerol and 1,2-diacylglycerol, or lotus flower essential oil, or a combination thereof 
     
     
         24 . A method of introducing pigments to the iris of a human subject, comprising administering to the iris an amount of a composition comprising a biological dye, effective to introduce pigment to the iris of the human subject. 
     
     
         25 . The method of  claim 24 , wherein the biological dye is a Trypan Blue or a Methyl Green biological dye. 
     
     
         26 . The method of  claim 24  or  25 , wherein the composition further comprises fluorescein. 
     
     
         27 . The method of  claim 26 , wherein the iris of the human subject changes color and/or glows. 
     
     
         28 . The method of any one of  claims 21 - 27 , wherein the composition is administered through a nanoparticle drug delivery system containing a targeting agent of iridial melanocytes. 
     
     
         29 . The method of  claim 28 , wherein the targeting agent comprises a composition of iron, zinc, gold, or a combination thereof. 
     
     
         30 . The method of  claims 29 , wherein the targeting agent comprises zinc oxide. 
     
     
         31 . A nanoparticle composition for lightening pigmented tissues, comprising a targeting agent of melanocytes chemically bound to a pharmaceutical composition comprising a tyrosinase inhibitor. 
     
     
         32 . The nanoparticle composition of  claim 31 , wherein the targeting agent comprises a composition of iron, zinc, gold, or a combination thereof. 
     
     
         33 . The nanoparticle composition of  claim 32 , wherein the targeting agent comprises zinc oxide. 
     
     
         34 . The nanoparticle composition of any one of  claims 31 - 33 , wherein the tyrosinase inhibitor is hydroquinone. 
     
     
         35 . The nanoparticle composition of any one of  claims 31 - 34 , wherein the pharmaceutical composition further comprises at least one melanogenesis inhibitor. 
     
     
         36 . The nanoparticle composition of any one of  claims 31 - 35 , wherein the pigmented tissues are skin or hair tissues. 
     
     
         37 . The nanoparticle composition of any one of  claims 31 - 36 , which is in the form of an injectable solution or a topically applied solution. 
     
     
         38 . A method for lightening pigmented tissues of a human subject, comprising administering the nanoparticle composition of any one of  claims 31 - 37  to the human subject so as to lighten the pigmented tissues, wherein the targeting agent binds to cells of the pigmented tissues to permit the release of the pharmaceutical composition directly into the cells of the pigmented tissues without affecting non-pigmented cells. 
     
     
         39 . A nanoparticle composition for treating a pigmented tissue related disease, comprising a targeting agent of melanocytes chemically bound to a pharmaceutical composition comprising an active agent for the disease. 
     
     
         40 . The nanoparticle composition of  claim 39 , wherein the targeting agent comprises a composition of iron, zinc, gold, or a combination thereof. 
     
     
         41 . The nanoparticle composition of  claim 40 , wherein the targeting agent comprises zinc oxide. 
     
     
         42 . The nanoparticle composition of any one of  claims 38 - 40 , wherein the disease is glaucoma or melanoma cancer. 
     
     
         43 . A method for treating a pigmented tissue related disease, comprising administering the nanoparticle composition of any one of  claims 38 - 42  to the subject so as to treat the disease, wherein the targeting agent binds to cells of the diseased pigmented tissue to permit the release of the pharmaceutical composition directly into the cells of the diseased pigmented tissue without affecting non-pigmented cells. 
     
     
         44 . A method of depigmenting the iris melanocytes to lighten the color of the iris, comprising the step of:
 a. Blocking the sympathetic and parasympathetic nerve supply to the melanocytes using botulinum toxin and memantine;   b. Preventing tyrosine conversion to melanin by one of available tyrosinase inhibitors;   c. Preventing Melanocyte-stimulating hormone activation (MSH) by using 2,5-Dimethyl-4-hydroxy-3(2H)-furanone (DMHF);   d. Inhibiting the COX-2 enzyme using NSAIDS;   e. Preventing melanogenesis by using a cholinergic agonist;   f. Blocking Alpha I-adrenergic receptors by using antagonist chemicals;   g. Transcriptional regulation of Melanogenic Enzymes by downregulation of MITF by Transforming Growth Factor (TGF) Family; or   h. Post-Transcriptional Modification of Melanogenic Enzymes by Inhibiting N-glycolysation of melanosomal enzymes, or a combination thereof, and using the subject matter of any one of the preceding claims for delivering depigmenting compositions to melanocytes in the iris.   
     
     
         45 . The method of  claim 44 , comprising the step of:
 a. Transcriptional regulation of Melanogenic Enzymes by downregulation of MITF by Transforming Growth Factor (TGF) Family; or   b. Post-Transcriptional Modification of Melanogenic Enzymes by Inhibiting N-glycolysation of melanosomal enzymes, or   c. a combination thereof   
     
     
         46 . The method of  claim 45 , comprising the step of:
 a. Transcriptional regulation of Melanogenic Enzymes by downregulation of MITF by Transforming Growth Factor (TGF) Family.   
     
     
         47 . The method of  claim 46 , wherein the downregulation of MITF is regulated by Transforming growth factor-beta1. 
     
     
         48 . The method of  claim 46 , wherein the downregulation of MITE is regulated by Transforming growth factor-beta2. 
     
     
         49 . The method of  claim 46 , wherein the downregulation of MITF is regulated by both Transforming growth factor-beta1 and Transforming growth factor-beta2. 
     
     
         50 . The method of  claim 45 , comprising the step of:
 Post-Transcriptional Modification of Melanogenic Enzymes by Inhibiting N-glycolysation of melanosomal enzymes   
     
     
         51 . The method of any one of  claims 1 - 30 ,  38  and  43 - 50 , wherein the medication is transported into the anterior chamber of the eye by microneedles. 
     
     
         52 . The method of any one of  claims 1 - 30 ,  38  and  43 - 50 , wherein the medication is transported into the anterior chamber of the eye by over-saturating the molecule carriers with the medication. 
     
     
         53 . The method of any one of  claims 1 - 30 ,  38  and  43 - 50 , wherein the medication is transported inside the melanocytes via Folate receptors. 
     
     
         54 . A composition for lightening pigmented tissues, comprising a targeting agent of melanocytes chemically bound to a pharmaceutical composition comprising a tyrosinase inhibitor. 
     
     
         55 . The composition of  claim 54 , wherein the targeting agent comprises a composition of iron, zinc, gold, or a combination thereof. 
     
     
         56 . The composition of  claim 55 , wherein the targeting agent comprises zinc oxide. 
     
     
         57 . The composition of any one of  claims 54 - 56 , wherein the tyrosinase inhibitor is hydroquinone. 
     
     
         58 . The composition of any one of  claims 54 - 57 , wherein the pharmaceutical composition further comprises at least one melanogenesis inhibitor. 
     
     
         59 . The composition of any one of  claims 54 - 58 , wherein the pigmented tissues are skin or hair tissues. 
     
     
         60 . The composition of any one of  claims 54 - 59 , which is in the form of an injectable solution or a topically applied solution. 
     
     
         61 . A method for lightening pigmented tissues of a human subject, comprising administering the composition of any one of  claims 54 - 60  to the human subject so as to lighten the pigmented tissues, wherein the targeting agent binds to cells of the pigmented tissues to permit the release of the pharmaceutical composition directly into the cells of the pigmented tissues without affecting non-pigmented cells. 
     
     
         62 . A composition for treating a pigmented tissue related disease, comprising a targeting agent of melanocytes chemically bound to a pharmaceutical composition comprising an active agent for the disease. 
     
     
         63 . The composition of  claim 62 , wherein the targeting agent comprises a composition of iron, zinc, gold, or a combination thereof. 
     
     
         64 . The composition of  claim 63 , wherein the targeting agent comprises zinc oxide. 
     
     
         65 . The composition of any one of  claims 62 - 64 , wherein the disease is glaucoma or melanoma cancer. 
     
     
         66 . A method for treating a pigmented tissue related disease, comprising administering the composition of any one of  claims 62 - 65  to the subject so as to treat the disease, wherein the targeting agent binds to cells of the diseased pigmented tissue to permit the release of the pharmaceutical composition directly into the cells of the diseased pigmented tissue without affecting non-pigmented cells.