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Medical use of fructose-1,6-bisphosphate and its blood drug concentration stabilizer composition

A technology of blood drug concentration and diphosphoric acid, which is used in drug combinations, medical preparations containing active ingredients, pharmaceutical formulations, etc. effect, reducing the effect of phosphoric acid poisoning

Active Publication Date: 2020-06-16
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Existing knowledge of the mechanism of action of FBP falls far short of explaining the wide range of pharmacological activities of FBP

Method used

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  • Medical use of fructose-1,6-bisphosphate and its blood drug concentration stabilizer composition
  • Medical use of fructose-1,6-bisphosphate and its blood drug concentration stabilizer composition
  • Medical use of fructose-1,6-bisphosphate and its blood drug concentration stabilizer composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1. Regulation of fructose-1,6-bisphosphate on the metabolism of normal cells and human astrocytes

[0054]Human normal astrocytes (HA) were cultured in media containing different concentrations of fructose-1,6-diphosphate trisodium salt (0mM, 0.25mM, 0.5mM, 1mM), and were cultured at 12h and 24h respectively. The level of lactic acid in the base and the level of ATP in the cells in 24h. The results showed that: compared with the control group, the lactic acid level of the treatment group at 12h and 24h decreased significantly with the increase of the concentration of fructose-1,6-diphosphate trisodium salt (the comparison between the treatment group and the control group ***P figure 1 a, b)

[0055] Human normal astrocytes (HA) were cultured in the medium containing 0.8mM fructose-1,6-diphosphate trisodium salt, and the intracellular 2,6- Protein levels of diphosphofructokinase 3 (PFKFB3), lactate dehydrogenase (LDH5), and cytochrome C (Cyto C) (β-actin was us...

Embodiment 2

[0060] Example 2. Tumor cells do not consume exogenous fructose-1,6-bisphosphate, but their glycolytic intermediates are significantly increased

[0061] Rat glioma cell lines (C6), human glioma cell lines (U87-MG, U-251, SHG-44) and patient-derived glioma cells (tumor 1, tumor 3) were treated with 1.6mM Cultured in the medium of fructose-1,6-diphosphate trisodium salt, the glycolysis intermediates glucose-6-phosphate G6P, fructose-1,6-diphosphate FBP, The levels of glyceraldehyde-3-phosphate (GAP), dihydroxyacetone phosphate (DHAP), and PGA 3-phosphoglycerate; in addition, the levels of fructose-1,6-bisphosphate in the 12h and 36h medium of each glioma cell line were measured s level. The experimental results showed that compared with the control group, the levels of glycolysis products FBP, GAP and DHAP in the fructose-1,6-bisphosphate treatment group were significantly increased (***P0.1) (Supplementary Table 1b). The experimental results show that tumor cells do not cons...

Embodiment 3

[0067] Example 3. Fructose-1,6-bisphosphate inhibits glycolysis of glioma cells

[0068] Human glioma cell lines (U87-MG, KNS-89, SHG-44) were cultured in medium containing 0.8mM and 1.6mM fructose-1,6-diphosphate trisodium salt and 1.6mM 2-deoxyglucose Medium culture, 12h, 24h, 36h, 48h measured the content of glycolysis end product lactic acid released by the cells in the culture medium respectively, the lactic acid level of the treatment group was significantly lower than that of the control group (CON) without drug addition (the treatment group was compared with the control group). ***P figure 2 ). The experimental results show that: 1,6-fructose diphosphate can inhibit the glycolysis of a variety of glioma cells.

[0069] Table 2a The relative level of lactic acid in glioma cells U87-MG after treatment with fructose-1,6-bisphosphate (compared with the control group)

[0070]

[0071] Table 2b The relative level of lactic acid in glioma cells KNS-89 after treatment wi...

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Abstract

The invention provides a medical application of fructose-1,6-bisphosphate and its blood drug concentration stabilizer composition, which is an application in the preparation of drugs for preventing and treating metabolic diseases and diseases related to metabolic dysfunction. The pharmaceutical form of FBP includes fructose-1,6-diphosphate protomorph and fructose-1,6-diphosphate and pharmaceutically acceptable salts and hydrates of prodrugs or derivatives thereof. The blood drug concentration stabilizer refers to a drug or substance for treating diabetes that can slow down the rapid degradation of FBP in the drug preparation in vivo. The present invention can produce higher FBP blood drug concentration peak value and more stable blood drug concentration and thus produce more significant drug effect, and can also reduce FBP dosage and reduce the toxicity caused by a large amount of inorganic phosphorus entering the systemic circulation after hydrolysis of a large dose of FBP , can improve the metabolic state through different mechanisms of action of FBP, and improve the clinical compliance of drugs through the synergistic drug effect mediated by different mechanisms of action.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to the use of fructose-1,6-diphosphate (also known as fructose-1,6-diphosphate and fructose diphosphate) and its blood drug concentration stabilizer composition in the preparation and prevention of metabolic diseases and diseases related to metabolic disorders The application of the medicine, the diseases include tumor, fatty liver, diabetes, hyperlipidemia, cardiovascular disease, peripheral neurological disease and central nervous system disease. Background technique [0002] Fructose-1,6-bisphosphate (FBP) is an intermediate product of sugar metabolism in the body. Exogenous FBP produces pharmacological effects by regulating the activity of several enzymes in sugar metabolism (fructose-bisphosphate Sodium tablet instructions, the second batch of chemical drug instructions published by the State Drug Administration in 2002). Exogenous FBP can increase the concentration of intracellular aden...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61K31/7024A61P3/00A61P35/00A61P3/06A61P1/16A61P3/10A61P9/00A61P25/02A61P25/00A61P25/08A61P25/28A61P25/16A61P25/18A61K31/155A61K38/28A61K31/4985
CPCA61K31/155A61K31/4985A61K31/7024A61K38/28A61K45/06A61K2300/00A61K9/209A61K9/5026A61P1/16A61P3/04A61P3/10A61P25/02A61P35/00A61P3/00A61P9/00A61P9/10A61P25/28A61P35/02
Inventor 连晓媛张治针胡誉怀毕洪运钱恒池彬彬
Owner ZHEJIANG UNIV
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