Amniotic membrane preparations and purified compositions and anti-angiogenesis treatment
Inventors
Tseng, Scheffer • He, Hua • Li, Wei
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9750772-B2
Publication Date
2017-09-05
Expiration Date
Abstract
Compositions having a combination of specific biological components have been found to exert a number of useful effects in mammalian cells, including modulating TGF β signaling, apoptosis, and proliferation of mammalian cells, as well as decreasing inflammation in mice. These components can be obtained commercially, or can be prepared from biological tissues such as placental tissues. Placental amniotic membrane (AM) preparations described herein include AM pieces, AM extracts, AM jelly, AM stroma, and mixtures of these compositions with additional components. The compositions can be used to treat various diseases, such as wound healing, inflammation and angiogenesis-related diseases.
Core Innovation
The disclosed invention relates to purified amniotic membrane and placental-derived preparations formed from frozen or previously frozen human placenta, including amniotic membrane jelly and amniotic stroma. These preparations comprise cross-linked high molecular weight hyaluronan together with tumor necrosis factor-stimulated gene 6, pentraxin-3, and thrombospondin-1, optionally comprising Smad7.
The disclosed compositions are described as water-soluble extracts of amniotic membrane derived from frozen or previously frozen placenta. They modulate TGF-b2 signaling, including dose-dependent suppression of TGF-b21 promoter activity, and are reported to reduce inflammation and apoptosis.
The anti-angiogenic activity is associated with the hyaluronan-linked complexes, including loss of TGF-b2 suppression after hyaluronidase digestion and enhanced suppression after lyophilization. Amniotic membrane stromal extract is described as exhibiting anti-angiogenic activity on vascular endothelial responses, with effects on HUVEC proliferation, apoptosis, VEGF-stimulated migration, and tube formation.
Claims Coverage
The independent claim covers a method of reducing angiogenesis by administering an amniotic membrane-derived water-soluble extract from frozen or previously frozen placenta that comprises four named components: TSG-6, PTX-3, TSP-1, and cross-linked high molecular weight hyaluronan. Dependent claims add refinements directed to angiogenesis-related disease scope, ophthalmic condition lists, an optional additional component, and multiple ocular routes and formats.
Frozen placenta-derived water-soluble amniotic membrane extract with specified components
Administering a water-soluble extract of amniotic membrane from frozen or previously frozen placenta, wherein the water-soluble extract comprises TSG-6, PTX-3, TSP-1, and cross-linked high molecular weight hyaluronan.
Angiogenesis-related disease target
The method is performed for an individual for treating an angiogenesis-related disease.
Tumor, cancer, or ophthalmological disease scope
The method is for treating an angiogenesis-related disease that is a tumor, cancer, or an ophthalmological condition.
Selected ophthalmological condition list
The ophthalmological condition is selected from corneal graft rejection, ocular neovascularization, retinal neovascularization, diabetic retinopathy, macular degeneration, retrolental fibroplasia, neovascular glaucoma, retinal ischemia, or vitreous hemorrhage.
Optional inclusion of Smad7
The extract additionally comprises Smad7.
Ocular administration routes and ocular insertion or implant formats
The composition is formulated for intraocular injection, subretinal injection, intravitreal injection, periocular injection, subconjunctival injection, retrobulbar injection, intracameral injection, sub-Tenon's injection, implantation, ocular implantation, or ocular insertion.
Overall claim coverage centers on reducing angiogenesis via administration of a frozen or previously frozen placenta-derived water-soluble amniotic membrane extract containing TSG-6, PTX-3, TSP-1, and cross-linked high molecular weight hyaluronan, with dependent claim refinements specifying angiogenesis-related disease, enumerated ophthalmic conditions, optional Smad7, and multiple ocular routes and insertion or implant formats.
Stated Advantages
Reducing angiogenesis.
Suppression of TGF-b21 promoter activity.
Reduction of inflammation and apoptosis.
Inhibition of angiogenesis, including anti-angiogenic activity on vascular endothelial responses.
Documented Applications
Cancer and angiogenesis-related conditions.
Ophthalmic neovascular disorders, including corneal graft rejection, diabetic retinopathy, macular degeneration, retinal neovascularization, retrolental fibroplasia, neovascular glaucoma, retinal ischemia, and vitreous hemorrhage.
Interested in licensing this patent?