Bile Acid and Fatty Acid Composition for Osteoporosis Treatment
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Solution Overview
Problem
Patients who have undergone gastric surgery, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), experience decreased vitamin D-induced calcium uptake and bone-mineral density (BMD) due to altered gastrointestinal anatomy, leading to complications like osteoporosis and secondary hyperparathyroidism, despite current supplementation regimens.
Innovation Solution
A composition comprising glycocholic acid or its salt, butyric acid or oleic acid, calcium, and vitamin D3, which synergistically induces the expression of vitamin D-receptor co-activator Hsp90β, enhancing calcium absorption and addressing the deficiencies in vitamin D-induced calcium transport.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If Roux-en-Y gastric bypass surgery is performed to treat morbid obesity, then weight loss and metabolic improvements are achieved, but intestinal calcium absorption is severely compromised and bone mineral density decreases
Solution Approach 1:
The patent uses a combination of bile acid (glycocholic acid or taurocholic acid) and fatty acid (butyric acid or oleic acid) as intermediary substances that mediate between the altered gastrointestinal environment post-surgery and the calcium absorption process. These compounds act as signaling molecules that restore the expression of vitamin D receptor co-activator Hsp90β and calcium transport proteins in the intestinal mucosa, thereby indirectly facilitating calcium absorption without directly transporting calcium themselves.
Solution Approach 2:
The invention changes the biochemical parameters of the intestinal environment by introducing specific bile acid and fatty acid combinations that modify the expression levels of key proteins (Hsp90β, TRPV6, claudin-2) involved in calcium transport. This parameter change restores the intestinal mucosa's responsiveness to vitamin D and its ability to absorb calcium, effectively counteracting the malabsorption caused by surgical anatomical changes.
2Quantity of substance
If sleeve gastrectomy is performed for weight loss and metabolic improvement, then gastric acid output is reduced and transit time is shortened, but calcium absorption ability is lowered
Solution Approach 1:
Similar to the RYGB approach, the patent employs bile acid and fatty acid compounds as intermediary signaling molecules that compensate for the reduced gastric acid environment and shortened transit time. These intermediaries restore the intestinal mucosa's protein expression profile (Hsp90β, TRPV6, claudin-2), enabling effective calcium absorption despite the altered gastric physiology and rapid transit conditions post-surgery.
3Quantity of substance
If vitamin D and calcium supplementation is provided to post-surgery patients, then calcium intake is increased, but intestinal calcium absorption remains deficient
Solution Approach 1:
The patent introduces bile acid and fatty acid compounds as essential intermediaries that bridge the gap between increased calcium intake and actual calcium absorption. These compounds restore the intestinal mucosa's absorptive capacity by upregulating vitamin D receptor co-activator Hsp90β and calcium transport proteins, thereby enabling the intestine to effectively utilize the supplemented calcium rather than simply increasing intake.
Solution Approach 2:
The invention employs a composite formulation combining multiple components (bile acid, fatty acid, vitamin D, and calcium) that work synergistically. The bile acid and fatty acid components restore the intestinal environment's responsiveness to vitamin D, while the vitamin D and calcium components provide the necessary nutrients, creating a composite system that overcomes the malabsorption barrier more effectively than individual supplements alone.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The composition effectively increases calcium absorption and prevents bone mineral density loss in patients post-gastric surgery and those with osteoporosis, by normalizing vitamin D-induced calcium transport and enhancing passive calcium passage, thereby addressing the challenges of malabsorption and bone health issues.
Implementation Method 1
a composition comprising at least one bile acid chosen from glycocholic acid or salt thereof, and at least one fatty acid chosen from butyric acid and oleic acid, or a salt thereof, synergistically induces expression of vitamin D-receptor co-activator Hsp90β and is followed by an increased calcium absorption
Implementation Method 2
Active vitamin D-induced calcium uptake normally occurs in the proximal small intestine, i.e. duodenum and first half of the jejunum
Implementation Method 3
a co-activator of the vitamin D receptor, heat-shock protein (Hsp) 90β, as well as the most important vitamin D-induced calcium transport protein, TRPV6, are down-regulated in the alimentary limb mucosa after RYGB
Implementation Method 4
Because of the re-routing of the gastrointestinal tract, with foregut exclusion of food passage through the stomach and duodenum, and rapid hindgut delivery of undigested food to the jejunum i.e. alimentary limb, micronutrient uptake is attenuated. The bypassed stomach secretes less hydrochloric acid and intrinsic factor (IF), negatively affecting e.g. iron and vitamin B12 uptake
Implementation Method 5
Functionally this condition partly mimics the effect of gastric bypass and thus lowers the ability for the mucosa to react on vitamin D and, in turn, reduces calcium absorption
Data Source
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AI summary
The present invention is related to a composition comprising at least one bile acid; at least one fatty acid or salt thereof, calcium, and vitamin D, for use as a medicament, and especially in inducing expression of vitamin D-receptor co-activator Hsp90β for increasing vitamin D-induced calcium uptake in a mammal. The invention is also related to a dietary or nutritional supplement comprising a composition as described above and comprising additionally conventional components for dietary or nutritional supplements.