Fixed-Dose Salt Combination for Cholestatic Liver Disease Therapy
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Solution Overview
Problem
Current treatments for liver diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are inadequate, with existing drugs like ursodeoxycholic acid (UDCA) showing insufficient therapeutic efficacy in 25%-50% of patients and obeticholic acid (OCA) causing safety issues, while there are no approved drugs for PSC, necessitating a novel therapy with better efficacy and safety.
Innovation Solution
A combination product comprising a compound of formula (I) or its pharmaceutically acceptable salt, in combination with a bile acid or derivative, formulated in specific molar ratios, to treat liver diseases and inflammatory bowel disease, including acid-base addition salts and pharmaceutical compositions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ursodeoxycholic acid (UDCA) is used as first-line treatment for PBC, then therapeutic coverage is achieved, but therapeutic efficacy is insufficient in 25%-50% of patients
Solution Approach 1:
The patent combines compound (I) with a bile acid or its derivative/analog (such as UDCA, OCA, or NorUDCA) into a fixed-dose combination product. This merging of two therapeutic agents aims to achieve synergistic effects, where compound (I) provides additional therapeutic benefit for patients who respond insufficiently to bile acid monotherapy, thereby improving overall therapeutic efficacy and expanding the responsive patient population.
2Reliability
If obeticholic acid (OCA) is used as second-line treatment for PBC, then therapeutic effects are significant, but safety issues arise including dyslipidemia and pruritus
Solution Approach 1:
The patent positions compound (I) as an intermediary therapeutic option that can be combined with bile acids to achieve significant therapeutic effects similar to OCA, but without OCA's harmful side effects. The fixed-dose combination allows compound (I) to mediate the therapeutic response while maintaining a safer safety profile regarding dyslipidemia and pruritus.
3Adaptability or versatility
If no approved drugs are available for PSC, then treatment options are limited, but this creates unmet clinical need
Solution Approach 1:
The patent designs compound (I) in combination with bile acids as a multi-functional therapeutic solution that addresses both PBC and PSC indications. The fixed-dose combination product is formulated to provide broad applicability across different cholestatic liver diseases, fulfilling unmet clinical needs in both approved (PBC) and unapproved (PSC) indications.
4Object-affected harmful factors
If higher requirements are placed on drug safety for hepatobiliary diseases, then patient safety is improved, but this limits treatment options
Solution Approach 1:
The patent creates a composite therapeutic formulation by combining compound (I) with bile acids in specific fixed doses. This composite product integrates the safety profile benefits of bile acids with the additional therapeutic benefits of compound (I), achieving a balanced formulation that meets high safety requirements while expanding treatment options through synergistic action.
Data Source
AI summary
A combined product, a pharmaceutical composition, a salt form and the use thereof in the treatment and/or prevention of diseases.