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Application of galactooligosaccharides and derivatives of galactooligosaccharides as SGLT inhibitor

A galacto-oligosaccharide and derivative technology, applied in application, food science, drug combination and other directions, can solve problems such as safety hazards, and achieve the effect of improving fatty liver, lowering blood lipid and fatty liver, and improving insulin resistance.

Pending Publication Date: 2020-02-21
OCEAN UNIV OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although carrageenan and its oligosaccharides have antiviral activity as a spray (public number CN102516323A, public number CN104546895A), oral administration has certain safety hazards (Shang Q., Toxicol Let., 2017, 279:87-95), Joan Laver gum and laver gum polysaccharides and oligosaccharides are very safe when taken orally, and are high-quality raw materials for the development of drugs and functional foods

Method used

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  • Application of galactooligosaccharides and derivatives of galactooligosaccharides as SGLT inhibitor
  • Application of galactooligosaccharides and derivatives of galactooligosaccharides as SGLT inhibitor
  • Application of galactooligosaccharides and derivatives of galactooligosaccharides as SGLT inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1: Containing 6-O-sulfate-β-1,3-D-galactose (Gal6S) and α-1,4-L-3,6-inner ether galactose (AnG) thiogaran oligosaccharide ( Preparation of SAOs), oligosaccharide alcohols (SAOs-OH) and oligosaccharide acids (SAOs-OOH).

[0040] Prepare 1000mg of sulfur agar polysaccharide with dilute sulfuric acid with a molar concentration of 0.1M to form a 10mg / mL aqueous solution, heat it to 60°C, stir and degrade it for 1.5 hours, neutralize it with an aqueous NaOH solution with a molar concentration of 2M after cooling, collect the supernatant by centrifugation, and then Add 3 volumes of 95% medical ethanol (concentration 95wt%) overnight at 4°C, centrifuge to collect the supernatant, remove the ethanol by rotary evaporation under reduced pressure, dialyze and desalt with a 200Da dialysis bag, concentrate by rotary evaporation, and freeze-dry to obtain SAOs. Take 100 mg of SAOs and dissolve it in 10 mL of 100 mM NaBH 4 The aqueous solution (containing NaOH with a molar con...

Embodiment 2

[0045] Example 2: Laver gum oligosaccharides (POs), oligosaccharide alcohols (POs) containing β-1,3-D-galactose (Gal) and 6-O-sulfate-α-1,4-galactose (Gal6S) -OH) and the preparation of oligosaccharide acids (POs-OOH).

[0046] Prepare laver gum with dilute sulfuric acid with a molar concentration of 0.1M to prepare a 10mg / mL aqueous solution, heat it to 80°C, stir and degrade it for 2.0 hours, neutralize it with an aqueous NaOH solution with a molar concentration of 2M after cooling, collect the supernatant by centrifugation, and add 4 times the volume 95% medical ethanol was placed overnight at 4°C, the supernatant was collected by centrifugation, and the ethanol was removed by rotary evaporation under reduced pressure, then desalted with a 200Da dialysis bag, concentrated by rotary evaporation, and freeze-dried to obtain laver gum POs. Take 150 mg of POs oligosaccharides and dissolve it in 15 ml of NaBH with a molar concentration of 150 mM 4 The aqueous solution (containin...

Embodiment 3

[0051] Example 3: Agar oligosaccharides containing β-1,3-D-galactose (Gal) and α-1,4-L-3,6-galactose (AnG) and their oligosaccharide alcohols and oligosaccharides acid preparation.

[0052] Dissolve the agarose in hot water, use dilute hydrochloric acid with a molar concentration of 0.1M to prepare a 10mg / mL solution, stir and degrade it at 80°C for 0.5 hours, neutralize it with an aqueous NaOH solution with a molar concentration of 2M after cooling, collect the supernatant by centrifugation, and then Add 2.5 times the volume of 95% medical ethanol at 4°C overnight, centrifuge to collect the supernatant, remove the ethanol by rotary evaporation, dialyze and desalt with a 200Da dialysis bag, concentrate by rotary evaporation and freeze-dry to obtain agar oligosaccharide AOs, and further reduce it with sodium borohydride to obtain agar Glucooligosaccharide alcohol AOs-OH, or agarooligosaccharide acid AOs-OOH obtained by oxidation with Benedict's reagent. The chemical structural...

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Abstract

The invention belongs to the field of marine medicine, and particularly relates to an application of oligosaccharides containing D-galactose and L-galactose and derivatives of the oligosaccharides asa sodium-glucose cotransporter (SGLT) inhibitor. The galactooligosaccharides and derivatives are prepared by the following steps: by using red algae polysaccharide containing the D- / L-galactose as a raw material, performing degradation by using a physical method, a chemical method, a bioenzyme method or any combination of the above methods to prepare the galactooligosaccharides and the derivativesof the galactooligosaccharides with different degrees of polymerization, wherein the molecular skeleton contains the D-galactose and the L-galactose and derivatives thereof. The raw material of the product provided by the invention is from the red algae polysaccharide, and has the advantages of rich resources, a simple preparation process, high safety, clear targets and easy industrialization, the oligosaccharides and the derivatives are used as the SGLT1 and 2 inhibitor, and has broad application prospects in the development of medicines for treating diseases such as diabetes mellitus, obesity, diabetic nephropathy and glucose and lipid metabolism disorder and functional foods for improving non-alcoholic fatty liver diseases.

Description

technical field [0001] The invention belongs to the field of marine medicines, in particular to the application of an oligosaccharide containing D-galactose and L-galactose and derivatives thereof as SGLTs (SGLT1 and SGLT2) inhibitors. Background technique [0002] Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia and absolute or relative insufficiency of insulin secretion by pancreatic β cells. In 2017, the number of diabetic patients in the world has reached 425 million, and it is expected to reach 629 million in 2045, while China has about 114.4 million diabetic patients, which has become the country with the largest number of patients; the prevalence rate of Chinese adults is 9.7%, and the prevalence of prediabetes The rate is as high as 15.5%, among which, more than 90% of patients are type 2 diabetes. Long-term chronic hyperglycemia leads to complications, causing large and small blood vessels and peripheral neuropathy, and causing damage...

Claims

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Application Information

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IPC IPC(8): A61K31/702A61K31/715A61P3/10A61P5/50A61P3/00A61P1/16A61P3/06A61P9/00A23L33/125C12C12/00C12C5/00C12P19/14C12P19/04C12P19/02C12P19/00
CPCA61K31/702A61K31/715A61P3/10A61P5/50A61P3/00A61P1/16A61P3/06A61P9/00A23L33/125C12C12/00C12C5/00C12P19/14C12P19/04C12P19/02C12P19/00A23V2002/00A23V2200/328A23V2200/326
Inventor 于广利王学良郝杰杰蔡超蒋昊李国云
Owner OCEAN UNIV OF CHINA
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