Amniotic membrane preparations and purified compositions and therapy for scar reversal and inhibition
Inventors
Tseng, Scheffer • He, Hua • Li, Wei
Assignees
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Publication Number
US-9724370-B2
Publication Date
2017-08-08
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 invention relates to amniotic membrane preparations and purified compositions for scar inhibition or reversal and broader therapeutic uses. Purified compositions comprise at least four defined components: cross-linked high molecular weight hyaluronan, tumor necrosis factor-stimulated gene 6, pentraxin-3, and thrombospondin-1, with optional Smad7. The compositions are described as modulating TGF-β signaling, including suppression of TGF-β1 promoter activity, and as influencing related cell phenotypes involved in fibrosis.
The described approach includes preparation and storage concepts for amniotic membrane-derived materials, including frozen or previously frozen placenta and amniotic membrane extract or related water-soluble extract. The description further addresses extraction and fractionation by centrifugation, with optional lyophilization and reconstitution. The compositions may be used as purified components alone or in combinations supported by example vehicles such as collagen/HA, as part of a therapeutic formulation scope.
The document also characterizes the composition activity in terms of hyaluronidase sensitivity and functional biological outcomes. It reports that hyaluronidase treatment is associated with loss of TGF-β suppression, and that enhanced activity is observed after lyophilization. Anti-scarring activity is supported by inhibition or reversal of myofibroblast differentiation and by effects on fibroblast migration, as described in tissue and cell models, alongside effects tied to inflammation, apoptosis, and fibrosis-related signaling and phenotypes.
Claims Coverage
Independent claim coverage centers on a scar-preventing or scar-reversing method that administers a specific amniotic membrane water-soluble extract from frozen or previously frozen placenta containing four named components: tumor necrosis factor-stimulated gene 6, pentraxin-3, thrombospondin-1, and cross-linked high molecular weight hyaluronan. Dependent claims add Smad7 and further narrow the composition and delivery options, including non-solid dosage forms, ocular delivery routes, penetration enhancer, aqueous adjuvant, and controlled release.
Administering an amniotic membrane water-soluble extract from frozen placenta for scar prevention or reversal
A method of preventing or reversing scar formation in a subject in need thereof by administering a composition comprising a water-soluble extract of amniotic membrane from frozen or previously frozen placenta.
Extract comprising TSG-6, PTX-3, TSP-1, and cross-linked high molecular weight hyaluronan
The water-soluble extract comprises tumor necrosis factor-stimulated gene 6, pentraxin-3, thrombospondin-1, and cross-linked high molecular weight hyaluronan.
Including Smad7 in the water-soluble extract
The method is further defined to include an extract that comprises Smad7.
Non-solid dosage form composition
The composition is formulated as a non-solid dosage form.
Ocular delivery route coverage for the composition
The composition is formulated for ocular delivery routes including intraocular, subretinal, intravitreal, periocular, subconjunctival, retrobulbar, intracameral, sub-Tenon's, implantation, ocular insertion, insertion between an eye and eyelid, and insertion in a conjunctival sac.
Penetration enhancer and aqueous adjuvant in the composition
The composition includes a penetration enhancer and an aqueous adjuvant.
Controlled release formulation
The composition is formulated for controlled release.
The core inventive concept is administration of an amniotic membrane water-soluble extract from frozen or previously frozen placenta containing tumor necrosis factor-stimulated gene 6, pentraxin-3, thrombospondin-1, and cross-linked high molecular weight hyaluronan for preventing or reversing scar formation. Coverage is broadened or refined by adding Smad7 and by specifying non-solid dosage forms, ocular delivery routes, penetration enhancer and aqueous adjuvant, and controlled release.
Stated Advantages
Inhibition or reversal of scar formation in a subject in need thereof.
Documented Applications
Wound healing.
Eye diseases.
Skin conditions.
Ophthalmic delivery, including ophthalmic drops and ointment as example formulations.
Topical skin lotion as an example formulation.
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