Compositions and methods for treating or preventing inflammatory bowel disease, familial adenomatous polyposis and colon cancer
Inventors
Assignees
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Publication Number
US-9987250-B2
Publication Date
2018-06-05
Expiration Date
Abstract
The present invention provides methods for preventing colon cancer by administering, to a patient in need thereof, a polymeric proanthocyanidin composition from a Croton species or Calophyllum species in an amount sufficient to prevent colon cancer, which composition inhibits COX-2. The present invention also provides methods for treating inflammation locally in the intestines comprising administering to a patient in need thereof, a polymeric proanthocyanidin composition from a Croton species or Calophyllum species in an amount sufficient to treat inflammation. In one embodiment, the polymeric proanthocyanidin compound is crofelemer. The present invention in alternative embodiments provides methods for treating pain locally in the intestines and treating inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, as well as for treating familial adenomatous polyposis (FAP).
Core Innovation
The invention relates to Croton species and Calophyllum species polymeric proanthocyanidin compositions, including crofelemer, for local intestinal treatment and/or prevention. The compositions are used to address inflammatory bowel disease and associated symptoms, including inflammation and pain locally in the intestines.
The document addresses the need to treat inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, while reducing unwanted systemic exposure. It states that crofelemer selectively inhibits COX-2 over COX-1 and is not substantially systemically absorbed when orally administered, and that this selectivity and limited systemic absorption are presented as ways to avoid cardiovascular side effects.
The invention further addresses dosing and formulation to support local intestinal activity using enteric protection. The compositions include oral and rectal forms and enteric-protected formulations, including enteric-coated tablets and enteric-coated particles in granular or powder forms.
Mechanistic data described in the document report inhibition of COX-1 and COX-2 enzymes at specified concentrations, and broad inhibition across multiple cytokine release assays and PGE2 release assays. Overall, the core approach is administering extracts from Croton or Calophyllum species at a dosing level bioequivalent to crofelemer to treat inflammation and pain associated with Crohn’s disease or ulcerative colitis.
Claims Coverage
The independent claims cover two treatment methods for inflammatory bowel disease, Crohn’s disease or ulcerative colitis: treating pain associated with inflammatory bowel disease and treating inflammation associated with inflammatory bowel disease. Each independent claim includes a shared inventive core of administering a Croton- or Calophyllum-species extract with a dosage bioequivalent to crofelemer 250 mg to 500 mg per day.
Bioequivalent Croton or Calophyllum extract for crofelemer dose range
Administering an extract from a Croton species or a Calophyllum species to a subject, wherein the dosage of the extract is bioequivalent to 250 mg to 500 mg of crofelemer per day.
Pain treatment for Crohn’s disease or ulcerative colitis
Treating pain associated with inflammatory bowel disease, wherein the inflammatory bowel disease is Crohn’s disease or ulcerative colitis.
Inflammation treatment for Crohn’s disease or ulcerative colitis
Treating inflammation associated with inflammatory bowel disease, wherein the inflammatory bowel disease is Crohn’s disease or ulcerative colitis.
Enteric-protected formulation formats
Providing the extract as an enteric-coated tablet or as granular/powder particles having an enteric coating.
Across the independent claims, the document’s claim coverage centers on using Croton- or Calophyllum-species extracts administered to produce treatment of pain and/or inflammation in Crohn’s disease or ulcerative colitis, with dosing bioequivalent to 250 mg to 500 mg per day of crofelemer, and with enteric-protected oral formulation formats.
Stated Advantages
Crofelemer selectively inhibits COX-2 over COX-1.
Crofelemer is not substantially systemically absorbed when orally administered.
The approach is aimed to avoid cardiovascular side effects.
Treatment provides quantitative improvement in pain-free days.
Inflammation is decreased by at least 20%.
Documented Applications
Local intestinal treatment and/or prevention of inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, directed to inflammation and associated pain.
Treatment of pain associated with inflammatory bowel disease (Crohn’s disease or ulcerative colitis).
Treatment of inflammation associated with inflammatory bowel disease (Crohn’s disease or ulcerative colitis).
Treatment and/or prevention statements for colon cancer and familial adenomatous polyposis (FAP) are described in the provided patent content.
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