权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of Novel Herbal Therapy for Prevention of Irinotecan-induced Severe Delayed Onset Diarrhea

开发预防伊立替康引起的严重迟发性腹泻的新型草药疗法

基本信息

批准号：
10335593
负责人：
Rashim Singh
金额：
$ 5.2万
依托单位：
SANARENTERO LLC
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-21 至 2022-09-20
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10335593
关键词：
Address American Cancer Society Antibiotics Antineoplastic Agents Attenuated Botanicals C57BL/6 Mouse Caco-2 Cells Cancer Patient Cause of Death Chemicals Chemistry Clinic Clinical Research Complementary therapies Data Development Diagnosis Diarrhea Disease Progression Disseminated Malignant Neoplasm Dose Dose-Limiting Encapsulated Ensure Enteral Event Fingerprint Flavonoids Formulation Freeze Drying Ginger Glucuronosyltransferase Granulocyte Colony-Stimulating Factor Heavy Metals Herb Hospitalization Human Incidence Individual Intestines Investments Legal patent Leukocytes Life Life Expectancy Loperamide Malignant Neoplasms Maximum Tolerated Dose Medical Morbidity - disease rate Mus Nausea and Vomiting Neoplasm Metastasis Neutropenia Oral Organ Palate Patients Pesticides Pharmaceutical Preparations Phase Phytochemical Phytotherapy Polymers Pre-Clinical Model Prevention Prevention therapy Procedures Process Property Quality Control Quality of life Recurrent disease Refractory Refractory Disease Research Resort SN-38 Safety Saiko Scutellaria Site Small Business Innovation Research Grant Source Standardization Survival Rate Suspensions Toxic effect Treatment Cost Tumor Suppression UGT1A1 gene United States Universities Uridine Validation analog anti-cancer base cancer therapy capsule chemotherapy clinical application compliance behavior cost effective therapy efficacy study experience improved in vivo in vivo evaluation innovation irinotecan microbial mortality novel novel therapeutics oriental phase 2 study prevent prophylactic protein expression refractory cancer side effect stability testing standard of care statistics success tumor growth wogonin

项目摘要

PROJECT SUMMARY / ABSTRACT Cancer is the second leading cause of death in the United States. According to American Cancer Society statistics, about 1.76 million new patients are expected to be diagnosed with cancer and about 600,000 people are expected to die due to cancer in the United States in 2019. Approximately 6-10% of the total cancer patients are diagnosed with stage IV/metastatic cancer, while 30-50% develop metastasis during disease progression. Through the advent of new and effective drugs for cancer treatment, 5-year survival rate for cancer has improved to about 67%, however treatment of refractory/recurrent disease in metastatic cancer patients remains a critical challenge. Among the various cancer drugs available for metastatic cancer treatment, irinotecan is often the drug of last resort for the refractory diseases. Recent clinical studies have indicated that high-dose irinotecan therapy can be successfully used in patients with refractory diseases, even in irinotecan-refractory patients, improving life expectancy of cancer patients. However, irinotecan treatment is currently limiting due to severe and sometimes life-threatening dose-limiting site effects (i.e. neutropenia and severe delayed onset diarrhea). Chemotherapy-induced neutropenia (low white blood cells) is effectively managed with prophylactic antibiotics and human G-CSF (granulocyte colony stimulating factor) agents in clinics. However, in about 15% of patients on standard of care irinotecan therapy, diarrhea is unmanageable with current drugs such as loperamide, requiring hospitalization and even cessation of therapy. Moreover, most current treatments only provide symptomatic relief but do not prevent the increasing damage to gut function and integrity, resulting with consecutive cycles of irinotecan therapy. Based on recent preliminary data from our collaborator’s lab, Sanarentero is proposing to develop a new herbal product (SE_H1) which can prevent the irinotecan-induced diarrheal toxicity and gut damage. This will help improve the quality of life, reduce the cost of treatment by reducing incidences of hospitalization, and increase the life expectancy of metastatic cancer patients with refractory/recurrent diseases, by allowing continuation of treatment and high-dose irinotecan therapy. The specific aims of this Phase I SBIR proposal are to 1) develop a standardized novel proprietary herbal formula using Caco-2 cells; 2) establish the in vivo efficacy of the proprietary herbal formula for SDOD prevention; and 3) standardize CMC (Chemistry, Manufacturing, and Controls) of SE_H1 for Phase II studies. Success of this project will generate a well-characterized, standardized, safe and efficacious proprietary herbal product for prevention of irinotecan-induced severe delayed onset diarrhea. It will also provide us with proof-of concept evidence of efficacy and safety in a preclinical model, therefore derisking the product for further development in phase II SBIR proposal.

项目摘要/摘要