Amniotic fluid topical formulation

Abstract

A human amniotic fluid formulation has been developed for topical application to the eye, which is useful for the treatment of ocular diseases and injuries including dry eyes, Sjogren's Syndrome, cataracts, burns and injuries to the eye tissues. The formulation is a sterile de-cellularized human amniotic fluid (D-HAF), devoid of amniotic stem cells and elements of micronized membrane or chorion particles. Methods for treating, or preventing various ocular diseases, injuries and disorders using the formulation, optionally in combination with one or more therapeutic, prophylactic or diagnostic agents are described.

I/We claim: 
     
         1 . A method for treating, alleviating, and/or preventing an ocular condition in a subject, the method comprising:
 topically administering to an eye of the subject an effective amount of a pharmaceutical composition and/or formulation comprising sterile serially-filtered de-cellularized human amniotic fluid (D-HAF), thereby treating, alleviating, and/or preventing one or more symptoms associated with the ocular condition,   wherein the sterile serially-filtered D-HAF is devoid of amniotic stem cells, elements of micronized membrane, and chorion particles,   wherein the D-HAF is sterilized only by filtration, and   wherein the ocular condition comprises one or more disorders associated with the eye.   
     
     
         2 . The method of  claim 1 , wherein the D-HAF is not treated by heat, not treated by any chemicals, and not treated by any irradiation. 
     
     
         3 . The method of  claim 1 , wherein the topically administering further comprises:
 administering to the eye one or more additional agents in combination with the pharmaceutical composition and/or formulation.   
     
     
         4 . The method of  claim 2 , wherein the one or more additional agents are selected from the group consisting of: an anti-glaucoma agent, an anti-angiogenesis agent, an anti-infective agent, an anti-inflammatory agent, an analgesic agent, a local anesthetic, a growth factor, an immunosuppressant agent, an anti-allergic agent, an anti-oxidant, a cytokine, and combinations thereof. 
     
     
         5 . The method of  claim 2 , wherein the one or more additional agents are selected from the group consisting of: paramagnetic molecules, fluorescent compounds, magnetic molecules, radionuclides, X-ray imaging agents, contrast media, and combinations thereof. 
     
     
         6 . The method of  claim 1 , wherein the D-HAF comprises one or more compounds selected from the group consisting of: growth factors, pro-inflammatory cytokines, anti-inflammatory cytokines, and combinations thereof. 
     
     
         7 . The method of  claim 1 , wherein the D-HAF comprises more than 50% of total amniotic factors relative to raw amniotic fluid. 
     
     
         8 . The method of  claim 7 , wherein the D-HAF comprises more than 90% of the total amniotic factors relative to the raw amniotic fluid. 
     
     
         9 . The method of  claim 1 , wherein the one or more disorders are selected from the group consisting of: dry eye disease, ocular burns, tears to the eye or associated structures, injury to the eye or the associated structures, corneal neovascular disorders, corneal opacities, corneal haze, ocular blast injuries, eye infections, eye surgeries, drug-induced eye conditions, prolonged redness of the eye, inflammation of the eye, and combinations thereof. 
     
     
         10 . The method of  claim 1 , wherein the one or more disorders are selected from the group consisting of: amoebic keratitis, fungal keratitis, bacterial keratitis, viral keratitis, onchorcercal keratitis, bacterial keratoconjunctivitis, viral keratoconjunctivitis, corneal dystrophic diseases, Fuchs' endothelial dystrophy, Sjogren's syndrome, Stevens-Johnson syndrome, autoimmune dry eye diseases, environmental dry eye diseases, corneal neovascularization diseases, post-corneal transplant rejection prophylaxis and treatment, autoimmune uveitis, infectious uveitis, anterior uveitis, posterior uveitis, toxoplasmosis, pan-uveitis, an inflammatory disease of the vitreous, an inflammatory disease of the retina, endophthalmitis prophylaxis and treatment, macular edema, macular degeneration, age-related macular degeneration, proliferative diabetic retinopathy, non-proliferative diabetic retinopathy, hypertensive retinopathy, an autoimmune disease of the retina, primary intraocular melanoma, metastatic intraocular melanoma, other intraocular metastatic tumors, open angle glaucoma, closed angle glaucoma, pigmentary glaucoma, and combinations thereof. 
     
     
         11 . The method of  claim 1 , wherein the one or more disorders are selected from the group consisting of: corneal injury, corneal burns, corneal abrasions, cataracts, age-related degeneration of the eye or vision associated therewith, and combinations thereof. 
     
     
         12 . A composition for treating, alleviating, and/or preventing an ocular condition in a subject, comprising:
 an effective amount of sterile serially-filtered de-cellularized human amniotic fluid (D-HAF); and   one or more pharmaceutically acceptable excipients,   wherein the D-HAF is devoid of amniotic stem cells, elements of micronized membrane, and chorion particles,   wherein the D-HAF is sterilized only by filtration, and   wherein the composition is formulated to be administered topically to an eye of the subject to treat, alleviate, and/or prevent the ocular one or more symptoms associated with the ocular condition.   
     
     
         13 . The composition of  claim 12 , wherein the composition is in a form selected from the group consisting of: a solution, a suspension, an ointment, a gel, a spray, a droplet, and combinations thereof. 
     
     
         14 . The composition of  claim 12 , wherein the composition is administered to the eye in combination with one or more additional agents selected from the group consisting of: an anti-glaucoma agent, an anti-angiogenesis agent, an anti-infective agent, an anti-inflammatory agent, an analgesic agent, a local anesthetic, a growth factor, an immunosuppressant agent, an anti-allergic agent, an anti-oxidant, a cytokine, and combinations thereof. 
     
     
         15 . The composition of  claim 12 , wherein the D-HAF is not treated with heat, and not treated with ethidium bromide. 
     
     
         16 . The composition of  claim 12 , wherein the D-HAF is treated by submicron filtration with a 0.22 micron low protein binding filter. 
     
     
         17 . The composition of  claim 12 , wherein the D-HAF comprises one or more growth factors selected from the group consisting of: epidermal growth factor (EGF), insulin-like growth factor I (IGF-I), vascular endothelial growth factor A (VEGF-α), tumor necrosis factor A (TNF-α), hepatocyte growth factor (HGF), fibroblast growth factor 7 (FGF7), matrix metallopeptidase (MMP-9), granulocyte-colony stimulating factor (GCSF), matrix metalloproteinase-7 (MMP-7), matrix metalloproteinase-7 (MMP-13), transforming growth factor alpha (TGF-α), transforming growth factor beta (TGF-β), fibroblast growth factor 4 (FGF-4), endocrine gland-derived vascular endothelial growth factor (EG-VEGF), interleukin 8 (IL-8), fibroblast growth factor 21 (FGF-21), angiopoietin-2 (ANG2), Glial cell-derived neurotrophic factor (GDNF), fibroblast growth factor 19 (FGF-19), TIMP metallopeptidase inhibitor 2 (TIMP-2), angiopoietin-1 (ANG-1), Transforming growth factor beta 1 (TGFβ1), macrophage colony-stimulating factor (M-CSF), angiotensinogen, platelet derived growth factor-AA (PDGF-AA), stem cell factor (SCF), and combinations thereof. 
     
     
         18 . The composition of  claim 12 , wherein the D-HAF comprises one or more pro-inflammatory cytokines selected from the group consisting of: Eotaxin-2 (CCL24), interleukin 6 (IL-6), pulmonary and activation-regulated chemokine PARC or chemokine (C-C motif) ligand 18 (CCL18), total GRO having three subunits GROα/CXCL1, GROβ/CXCL2, and GROγ/CXCL3, expression of the neutrophil-activating CXC chemokine (ENA-78/CXCL-5), chemokine (C-C motif) ligand 21 (CCL21 or 6Ckine), macrophage inflammatory protein 3 alpha (MIP-3α or CCL20), monokine induced by gamma (MIG or CXCL-9), MIP-1α, chemokine (C-C motif) ligand 5 (CCL-5), Interleukin-1 alpha (IL-1a), macrophage inflammatory protein-1β (MIP-1β or CCL4), tumor necrosis factor (TNFα), monocyte chemotactic protein 2 (MCP-2 or CCL8), and combinations thereof. 
     
     
         19 . The composition of  claim 12 , wherein the D-HAF comprises one or more anti-inflammatory cytokines selected from the group consisting of: interleukin 8 (IL-8), interleukin 13 (IL-13), interleukin 27 (IL-27), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), vascular endothelial growth factor D (VEGF-D), interleukin-1 receptor antagonist (IL-1Ra), transforming growth factor beta 1 (TGFβ1), interleukin 5 (IL-5), interleukin 21 (IL-21), and combinations thereof. 
     
     
         20 . A composition for treating, alleviating, and/or preventing an ocular condition in a subject, comprising:
 an effective amount of sterile serially-filtered de-cellularized human amniotic fluid (D-HAF),   wherein the D-HAF is devoid of amniotic stem cells, elements of micronized membrane, and chorion particles,   wherein the D-HAF is not treated by heat, not treated by chemicals, and not treated by gamma-irradiation,   wherein the D-HAF is sterilized only by filtration,   wherein the D-HAF is administered with or without implementation of an implant, and   wherein the D-HAF is administered in a form selected from the group consisting of: a solution, a suspension, an ointment, a gel, a spray, a droplet, and combinations thereof.