Somatostatin Analog Combinations for Receptor Selectivity and Hyperglycemia Control
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Solution Overview
Problem
Somatostatin analogs targeting SSTR5 often cause hyperglycemia as a side effect due to strong activation of SSTR5, while those targeting SSTR2 may not effectively reverse this hyperglycemia, limiting their use in treating diseases mediated by somatostatin receptors.
Innovation Solution
A combination of somatostatin analogs predominantly targeting SSTR2 and SSTR5, such as octreotide and pasireotide, is used to maintain hormone secretion inhibition with reduced hyperglycemic effects, allowing for higher doses or lower doses of each analog to achieve synergistic efficacy without increased glucose levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If somatostatin analogs predominantly targeting SSTR5 are used, then hormone secretion inhibition is improved, but hyperglycemic side effects increase
Solution Approach 1:
The patent combines somatostatin analogs with different selectivity profiles (SSTR2-predominant and SSTR5-predominant) into a single therapeutic regimen. This merging allows the SSTR2-targeting analog to counteract the hyperglycemic effects of the SSTR5-targeting analog while maintaining synergistic hormone secretion inhibition, thus resolving the contradiction between efficacy and side effects
Solution Approach 2:
The patent changes the parameter of receptor subtype selectivity by using a combination of analogs with different selectivity profiles rather than a single analog. This parameter change allows optimization of the therapeutic effect while minimizing adverse effects by balancing SSTR2 and SSTR5 activation
2Productivity
If higher doses of SSTR5-targeting analogs are used to enhance hormone secretion inhibition, then therapeutic efficacy is improved, but hyperglycemic side effects worsen
Solution Approach 1:
By merging SSTR2-targeting and SSTR5-targeting analogs in a fixed combination, the patent enables use of higher doses of SSTR5-targeting analogs for enhanced efficacy while the concurrent SSTR2-targeting analog mitigates the dose-dependent hyperglycemic effects, thus improving productivity without worsening harmful factors
3Adaptability or versatility
If somatostatin analogs with broad SSTR1-5 selectivity are used, then multiple physiological effects are achieved, but hyperglycemia occurs due to SSTR5 activation
Solution Approach 1:
The patent segments the broad-spectrum somatostatin activity into two distinct components: one analog primarily targeting SSTR2 and another primarily targeting SSTR5. This segmentation allows selective activation of desired physiological effects while using the SSTR2 component to counterbalance the hyperglycemic effects of SSTR5 activation, thus maintaining versatility while reducing harmful factors
Data Source
AI summary
The present invention relates to a combination of two or more Somatostatin (SRIF) peptidomimetics (also referred to as Somatostatin- or SRIF-analogs) which have different selectivity for the five human somatostatin receptor subtypes, the use of such combination in the treatment of a disease mediated by activation of somatostatin receptors, and to pharmaceutical compositions comprising such a combination.