Methods and compositions for treating congenital diarrhea disorder
Inventors
Conte, Lisa A. • Chaturvedi, Pravin R.
Assignees
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Publication Number
US-11857510-B2
Publication Date
2024-01-02
Expiration Date
Abstract
Presented herein are methods and compositions for treating congenital diarrheal disorders (CDD). Methods comprise administering to a patient in need thereof, an effective amount of a proanthocyanidin polymer composition from C. lechleri, preferably crofelemer. Administration of the proanthocyanidin polymer composition addresses the secretory diarrhea and symptoms associated therewith caused by the CDD and can improve nutritional status, electrolyte balance, hydration, growth and development of the patient.
Core Innovation
The invention relates to treating congenital diarrheal disorders, in particular secretory diarrhea forms characterized by fluid accumulation irrespective of fasting (ion gap <50). The disclosure addresses treating secretory diarrhea associated with Microvillous Inclusion Disease (MVID) in a subject by administering an isolated proanthocyanidin polymer from Croton lechleri, preferably crofelemer, effective to treat the secretory diarrhea associated with MVID.
The disclosure links crofelemer to topical gastrointestinal action via CFTR and calcium-activated chloride channel inhibition. By inhibiting calcium-activated chloride channels and involving CFTR-related mechanisms, the described treatment is intended to improve secretory diarrhea symptoms in the MVID setting. The disclosure further describes treatment contexts and disease subtypes within congenital diarrheal disorders, including forms such as MVID, CTE, THES, IPEX/IPEX-like, CSD, CCD, and PBAM.
The described intended clinical improvements include reduced diarrhea and reduced stool frequency with reduced watery stools, improved abdominal pain/discomfort and improved stool consistency. Additional supportive benefits described include improved hydration, electrolyte balance, nutritional status, growth/development, and reduced dependence on parenteral nutrition, bowel resection, bowel transplant, or hematopoietic stem cell transplantation. The disclosure also includes pharmaceutical compositions and enterically protected delivery concepts.
Claims Coverage
The provided claim content includes one independent claim directed to treating secretory diarrhea associated with Microvillous Inclusion Disease (MVID). The inventive features are centered on administering an isolated Croton lechleri proanthocyanidin polymer composition effective for MVID-associated secretory diarrhea, with dependent claim refinements for crofelemer identity, aqueous vehicle delivery, dosing and frequency, symptom-onset timing, human infant subject population, and treatment-response criteria.
Treating secretory diarrhea associated with MVID using Croton lechleri proanthocyanidin polymer
A method of treating secretory diarrhea associated with Microvillous Inclusion Disease (MVID) in a subject by administering an amount of a composition comprising isolated proanthocyanidin polymer from Croton lechleri effective to treat the secretory diarrhea associated with MVID.
Crofelemer in an aqueous vehicle for MVID-associated secretory diarrhea
The isolated proanthocyanidin polymer from Croton lechleri is crofelemer, and the composition is administered in an aqueous vehicle.
Dose range for crofelemer
Administering an amount of the aqueous vehicle composition providing a daily dose ranging from 2 mg/kg to 10 mg/kg per day.
Administration frequency constraints
Administering the composition effective to treat secretory diarrhea associated with MVID with dosing per day in a schedule selected from two times per day, three times per day, or four times per day.
Treating after onset of MVID symptoms
Administering the composition after a subject starts showing symptoms of MVID.
Human infant subject population
The subject is a human infant.
Defining treatment success by specified clinical improvements
The subject is considered treated when one or more specified treatment-response improvements are observed, including decreased bowel movement frequency, decreased watery bowel movements, improved daily abdominal pain/discomfort score, or improved daily stool consistency score.
The claim coverage centers on administering an isolated proanthocyanidin polymer from Croton lechleri, preferably crofelemer, to treat MVID-associated secretory diarrhea, with refinements specifying aqueous vehicle delivery, dosing, frequency, timing after symptom onset, human infant subjects, and explicit clinical endpoints used to define treatment success.
Stated Advantages
Reduced diarrhea and reduced stool frequency, including reduced watery stools.
Improved abdominal pain/discomfort.
Improved stool consistency.
Improved hydration and electrolyte balance.
Improved nutritional status, growth, and development.
Reduced dependence on parenteral nutrition, bowel resection, bowel transplant, or hematopoietic stem cell transplantation.
Documented Applications
Treating secretory diarrhea associated with Microvillous Inclusion Disease (MVID) in a subject by administering isolated proanthocyanidin polymer from Croton lechleri, preferably crofelemer.
Treatment context within congenital diarrheal disorders (CDD), including secretory diarrhea forms characterized by fluid accumulation irrespective of fasting (ion gap <50), with disease subtypes described such as CTE, THES, IPEX/IPEX-like, CSD, CCD, and PBAM.
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