Method of treating fibrosis
Inventors
Jung, Hoe Yune • Jeon, Jong Su • LEE, Do Hyun • LEE, Heon Jong
Assignees
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Publication Number
US-12053467-B2
Publication Date
2024-08-06
Expiration Date
Abstract
A new use of a cyclo(His-Pro) is disclosed. In particular, a method for treating fibrosis and/or inflammation which includes administering an effective amount of an isolated cyclo (His-Pro) to a subject in need thereof is disclosed.
Core Innovation
The disclosure provides a method for treating idiopathic pulmonary fibrosis by administering an effective amount of a composition comprising cyclo(His-Pro) hydrate to a subject in need thereof. The compositions include cyclo(His-Pro) hydrate, including embodiments where the composition is a solid composition consisting essentially of cyclo(His-Pro) hydrate alone or cyclo(His-Pro) hydrate together with zinc.
The disclosure describes a rationale for the treatment based on downregulating fibrosis markers, including ECM components such as fibronectin and collagens, α-SMA, and TGF-β, and reducing hydroxyproline deposition. In exemplary embodiments, the effects include reductions in hydroxyproline in lung and reductions in fibrotic remodeling markers associated with TGF-β/ECM remodeling.
Embodiments include administration with or without zinc, including sequential or simultaneous cyclo(His-Pro) hydrate and zinc administration, and characterizing cyclo(His-Pro) hydrate via XRPD peak ranges and other purity/stability attributes. The document additionally reports in vivo evidence in a bleomycin-induced pulmonary fibrosis mouse model showing decreased mRNA and protein levels for fibronectin, α-SMA, collagens, and TGF-β, decreased IL-6, and decreased lung hydroxyproline after cyclo(His-Pro) hydrate treatment, with enhanced or added effects for cyclo(His-Pro) hydrate plus zinc compared with cyclo(His-Pro) alone.
Claims Coverage
The independent claim provides direct coverage for treating idiopathic pulmonary fibrosis by administering an effective amount of a cyclo(His-Pro) hydrate composition, and the dependent claims refine the coverage through multiple inventive features, including formulation as a solid composition with or without zinc, specified zinc dosing and zinc chemical forms, specified cyclo(His-Pro) hydrate effective daily dosage ranges, and XRPD-based characterization of a crystalline cyclo(His-Pro) hydrate.
Treating idiopathic pulmonary fibrosis with cyclo(His-Pro) hydrate
Administering an effective amount of a composition comprising a cyclo(His-Pro) hydrate to a subject in need thereof, wherein the fibrosis is idiopathic pulmonary fibrosis.
Solid composition of cyclo(His-Pro) hydrate with or without zinc
Providing a composition as a solid composition consisting essentially of either cyclo(His-Pro) hydrate alone or cyclo(His-Pro) hydrate together with zinc.
Daily zinc cation dosing
Administering zinc to the subject at a daily dose within one of several specified ranges calculated as zinc cation.
Zinc chemical forms
Using zinc that is either a zinc ion, zinc metal, or a selected zinc salt from a specified list.
Effective daily cyclo(His-Pro) hydrate dose (anhydrous basis)
Administering an effective daily amount of cyclo(His-Pro) hydrate calculated as anhydrous cyclo(His-Pro), within one of the listed dosage ranges.
XRPD characterization of crystalline cyclo(His-Pro) hydrate
Carrying out the method using a crystalline cyclo(His-Pro) hydrate characterized by an XRPD diffractogram with peaks at specified 2θ values.
Overall, the claim set covers treating idiopathic pulmonary fibrosis using cyclo(His-Pro) hydrate, with dependent coverage narrowing to specific solid formulations, zinc co-administration including dosing and zinc forms, specified cyclo(His-Pro) hydrate effective daily amounts, and XRPD-defined crystalline cyclo(His-Pro) hydrate.
Stated Advantages
Downregulates fibrosis markers including ECM components (fibronectin and collagens), α-SMA, and TGF-β.
Reduces hydroxyproline deposition in the lung.
Reduces IL-6 in the bleomycin-induced pulmonary fibrosis model.
Shows enhanced or added effects when cyclo(His-Pro) hydrate is administered together with zinc compared with cyclo(His-Pro) alone.
Documented Applications
Treatment of idiopathic pulmonary fibrosis by administering cyclo(His-Pro) hydrate to a subject in need thereof.
Use in a bleomycin-induced pulmonary fibrosis mouse model, where cyclo(His-Pro) hydrate treatment reduces fibrotic and inflammatory markers and decreases lung hydroxyproline.
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