Pharmaceutical compositions of Anisomelic acid and the use thereof
Inventors
Eriksson, John E. • Paul, Preethy • Peuhu, Emilia • Akbarsha, M. A.
Assignees
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Publication Number
US-9623002-B2
Publication Date
2017-04-18
Expiration Date
Abstract
A pharmaceutical composition for anti-viral cancer treatment in mammals, comprising a therapeutically effective amount of Anisomelic acid or salts thereof. The pharmaceutical composition may comprise Anisomelic acid or salt thereof in an oil-in-water emulsion, for example in an isotropic mixture of at least one oil and at least one surfactant or, alternatively, in a hydrophilic solvent and a co-solvents or surfactant or a combination thereof. A method of treating or preventing of cancer in a mammal, wherein the p53 pathway is deregulated by viral oncoproteins, is also provided.
Core Innovation
The document discloses pharmaceutical compositions and therapeutic use of anisomelic acid (AA) and pharmaceutically acceptable salts and derivatives for anti-viral and anti-cancer treatment, with emphasis on Human Papilloma Virus (HPV) mediated cancers. It states that AA inhibits HPV16 E6/E7 oncoprotein expression, reactivating p53/p21 signaling and inducing G2/M cell-cycle arrest in HPV-mediated cancer contexts.
The document further states that AA induces p53-independent apoptosis. The disclosed mechanism includes down-regulation of cIAP2 and intrinsic mitochondrial apoptosis characterized by caspase-9 and caspase-3 activation, with PARP cleavage, and it contrasts HPV-positive and HPV-negative settings using mechanistic experimental findings across indicated cell lines.
In addition, the document reports improved efficacy and non-toxicity when AA is formulated in oil-in-water emulsion, oil-in-water microemulsion, and SMEDDS-type systems. It also reports in vivo tumor suppression using a topical AA emulsion in a chorioallantoic membrane (CAM) tumor model, and the disclosed use is extended to HPV-related genital warts and other HPV-mediated diseases.
Claims Coverage
The partial claim set includes two independent claims. Together, they cover administering anisomelic acid or salts to treat HPV-mediated cancers and HPV associated benign or neoplastic diseases, with subsets that specify particular disease types and at least one administration mode.
Treating HPV mediated cancers by administering anisomelic acid
A method of treating Human Papilloma Virus mediated cancers in a human by administering a therapeutically effective amount of anisomelic acid or salts thereof.
Treating HPV associated diseases by administering anisomelic acid
A method of treating benign or neoplastic Human Papilloma Virus associated diseases comprising administering a therapeutically effective amount of anisomelic acid or salts thereof to said human.
Across the independent claims, anisomelic acid or salts thereof is administered as a therapeutically effective amount for HPV mediated cancer treatment and for benign or neoplastic HPV associated diseases.
Stated Advantages
Improved efficacy with AA formulated as oil-in-water emulsion, oil-in-water microemulsion, and SMEDDS-type systems.
Non-toxicity is reported with the AA formulations.
Induction of early apoptosis is reported with the described formulations.
CAM tumor suppression is reported with topical AA emulsion.
Documented Applications
Therapeutic treatment of Human Papilloma Virus mediated cancers, including cervical cancer and oropharyngeal cancer.
Therapeutic treatment of HPV associated benign or neoplastic diseases, including benign HPV-mediated warts and HPV-mediated genital warts.
Topical administration of anisomelic acid or salts in the chorioallantoic membrane (CAM) tumor model is documented.
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