Potassium ion binding polymers for pharmaceutical compositions
An acrylic polymer, application technology, applied in the direction of synthetic polymer material active ingredients, drug combination, drug delivery, etc., can solve the problem of diuretic efficacy limitation and the like
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Embodiment 1
[0220] Example 1: Preparation of polymers with high binding energy
[0221] All chemicals were purchased from commercial sources and all chemical reactions were performed under nitrogen atmosphere. The chemical structural formulas and corresponding abbreviated symbols are listed in Tables 6 and 7.
[0222] Table 6. Abbreviated symbols and structural formulas of monomers
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[0225] Table 7. Abbreviated symbols and structural formulas of crosslinking agents
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[0228] Initiator: VA-044: 2,2'-Azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride; K 2 S 2 o 8 , Potassium persulfate.
[0229] General method for preparing gels from FAA:
[0230] First, add FAA, X-V-1 and water into a 15mL test tube, then put a magnetic stir bar. The mixture was stirred at 45°C for 20 minutes. Then, VA-044 (100 mg / mL in water) was added to colloid the solution and kept at 45° C. for 4 hours, and then cooled to room temperature.
[0231] The gel wa...
Embodiment 2
[0254] Embodiment 2: binding energy screening method
[0255] All experiments were performed in duplicate. Two aliquots of approximately 30 mg each were placed in glass test tubes of 16 x 100 mm for each polymer. Dowex 50W and Amberlite CG-50 were included in each assay as internal controls. The relevant assay binding buffer (buffer 1, buffer 2 or buffer 3 see below) was added to a final resin concentration of 2.5 mg / mL. After the test tube was sealed with a Teflon membrane, it was incubated at room temperature while continuously rotating upside down for at least 1 hour, so that the combination of the cation and the polymer reached equilibrium. The tube was then centrifuged at 500 g for 30 minutes to separate the resin. Take the supernatant sample and use ion chromatography (IC) to determine potassium (K + eq ) and sodium (Na + eq ) at the equilibrium concentration. Will K + eq and Na + eq Concentration (K + 起始 and Na + 起始 ) for comparison, the binding energy...
Embodiment 3
[0276] Example 3: Method for predicting cation binding in the human gastrointestinal tract
[0277] This method is used to simulate the use conditions of potassium-binding drugs, and to determine the binding characteristics of polymers for potassium (target solute) in the presence of other competing cations. Mock food was prepared and simulated digestion was performed in the presence of pepsin and pancreatic juice. Both the order of enzyme addition and the pH profile were controlled to simulate digestion down to the jejunum. Lithium-preloaded polymers were added to the digested simulated food and left for a period of time to allow equilibrium to be achieved. Then the mixture was centrifuged, and the supernatant was taken. Determination of Na by ion chromatography + 、K + , NH 4 + , Ca 2+ and Mg 2+ . Lithium liberated was calculated as total cation exchange, while decreased concentrations of other cations were used to calculate their binding variables in Western foods...
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