CN1057299C - Sodium magnesium D-fructose-1,6-diphosphate and its preparation method and application - Google Patents
Sodium magnesium D-fructose-1,6-diphosphate and its preparation method and application Download PDFInfo
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- CN1057299C CN1057299C CN98112218A CN98112218A CN1057299C CN 1057299 C CN1057299 C CN 1057299C CN 98112218 A CN98112218 A CN 98112218A CN 98112218 A CN98112218 A CN 98112218A CN 1057299 C CN1057299 C CN 1057299C
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Abstract
The present invention relates to a compound D-fructose-1, 6-natrium magnesium diphosphate with a novel structural formula I, a preparation method thereof and applications of the novel compound used as an effective ingredient in medicines for treating myocardial ischemia and hypertension.
Description
The present invention relates to new Compound D-fructose-1,6-diphosphate sodium magnesium (Sodium Magna-sium-D-Fructose-1,6-diphosphate), its preparation method and this new compound be as the purposes of effective ingredient in preparation treatment myocardial ischemia medicine and antihypertensive drug.
Structural formula is the D-fructose-1,6-diphosphate (D-Fructose-1,6-Diphos-phoric Acid) of II,, be glycometabolic important intermediate in the body, and have the effect of regulating some enzymes in the carbohydrate metabolism.The D-fructose-1,6-diphosphate can improve the energy metabolism under the tissue ischemia anoxia condition, and promptly FDP can be histocyte the energy is provided, and has the effect of metabolic regulation agent again, activates some enzymes, alleviates the cell glucose metabolism disorder.But formula II itself is very unstable, realizes its pharmaceutical use difficulty.The known structure formula is the D-fructose-1 of III, 6-trisodium phosphate salt (D-Fructose-1,6-diphosphate trisodium Salt), effect with ischemic hypoxia diseases such as treatment myocardial ischemias, and as pharmaceutical applications (Diana Massimo, Ger Offen DE 3446927,1985).
Mg
2+Being important ion necessary in the body, is that many enzymes keep active in the body, indispensable a kind of coenzyme, i.e. Mg
2+The histocyte function there are adjusting and participation effect.Function can produce calmness, anticonvulsant action to central nervous system in its body; Lax vascular smooth muscle and step-down, coronary artery dilating; Reduce catecholamine and discharge the treatment irregular pulse; Prevent digitalism etc.And the present clinical Mg that replenishes
2+Be sal epsom, can not provide the energy, so that histocyte can produce dysfunction because of energy deficiency in pathological process for body.
Remove known sal epsom at present and treating Acute Myocardial Infarction as medicine, outside clinical application, do not see has document not report this compound of D-fructose-1,6-diphosphate sodium magnesium to myocardial ischemia, and the application in treatment myocardial ischemia and antihypertensive drug.
The D-fructose-1 of the compound of existing preparation structural formula II in the prior art, the method of 6-bisphosphate, as the Matti Leisala of Univ Helsinki Finland in " Acta ChemicaScandinavica " B disclosed employing in 28 1974 years with glucose, phosphoric acid salt and cereuisiae fermentum are main raw material, obtain the method for D-fructose-1,6-diphosphate of the compound of structural formula II through the continuous phosphorylation reaction of enzymatic.
Purpose of the present invention: one provides the Compound D-fructose-1,6-diphosphate sodium magnesium of novel therapeutic myocardial ischemia and antihypertensive function; Two provide the industrial short-cut method of this compound of preparation as medicine, and the 3rd, this compound is as the purposes of effective ingredient in preparation treatment myocardial ischemia medicine and antihypertensive drug.
The Compound D of novel therapeutic myocardial ischemia provided by the invention and antihypertensive function-fructose-1,6-diphosphate sodium magnesium is characterized in that:
What the method for preparing compound in structural formula I provided by the invention adopted is such step: promptly at first 5～10% glucose, 6～8% phosphoric acid salt, 40～60% cereuisiae fermentum and excess water are prepared into mixing solutions, regulate pH value to 5～6, the fermented liquid that obtains through four hours continuous phosphorylation reactions of enzymatic, after removing yeast and protein, get supernatant liquor and adjust pH value to 8～9, discard precipitation, add CaCl
2Solution, the fructose diphosphate calcium raw product that must have a large amount of precipitations to produce, dissolution precipitation, discard insolubles, supernatant liquor is adjusted pH value to 8, collecting precipitation, get fructose diphosphate calcium white powder after the drying, after its dissolving, make fructose diphosphate calcium by storng-acid cation exchange resin, change into structure I I formula fructose diphosphate; With itself and magnesium oxide or the reaction of alkali formula magnesium salts, neutralize with it with sodium hydroxide again, add then in the ethanol, stir, centrifugal, treat precipitation produce after again with ethanol to its recrystallization, xln is carried out promptly getting compound in structural formula I after the drying at last.
Aforesaid method of the present invention can further specify by drawings and Examples.
Accompanying drawing is the process flow sheet of the embodiment of the invention.
At first prepare fermented liquid, 1 liter of preparation of fermentation liquid: comprise 5～10% glucose, phosphoric acid salt 6～8%, cereuisiae fermentum 400～600 grams are with pH value to 5～6 of sodium hydroxide adjustment solution, under 40 ℃ temperature, through four hours fermentations promptly.1.5 liters of fermented liquids are centrifugal, discard yeast., centrifugal with 20% Tricholroacetic Acid precipitation to remove deproteinize, get supernatant liquor and add ammoniacal liquor adjusting pH value to 8～9, there is precipitation to generate.The centrifugal precipitation that discards.Under agitation add about 200ml50%CaCl
2Solution promptly has a large amount of precipitations to generate, and gets fructose diphosphate calcium raw product; Place 200ml distilled water to stir raw product, slowly drip the 1M hydrochloric acid soln to resolution of precipitate; Centrifugal, discard insolubles.Add sodium hydroxide solution in the supernatant liquor to pH value 8.0, centrifugal, collecting precipitation.Repetitive operation once.Filtration under diminished pressure, collecting precipitation are dry in vacuum drier, obtain fructose diphosphate calcium white powder after the drying, nearly weigh 40g.Be about 50% by fructose diphosphate calculated yield in the fermented liquid.Get the fructose diphosphate calcium 50g of purifying, place 250ml distilled water to stir, add storng-acid cation exchange resin and make the decalcification of fructose diphosphate calcium, change into fructose diphosphate II, after magnesium oxide or the reaction of alkali formula magnesium salts, with the sodium hydroxide neutralization, add in the ethanol, question response finishes, centrifugal, precipitation is used the ethanolic soln recrystallization, can get 40 gram compound in structural formula I D-fructose-1,6-diphosphate sodium magnesium after the drying.The product content of highly narrow spectrum enzymatic assays fructose diphosphate II.Wherein enzyme reagent adopts glycerolphos phate dehydrogenase one triosephosphate isomerase suspension (GDH/TIM), nicotinamide adenine dinucleotide reduced (NADH), zymohexase (Aldolose).Use the chemical determination metal ion content.The result is: fructose diphosphate II71.0%, magnesium 6.2%, sodium 5.4%, crystal water 17.4%.Press C
6H
10O
12P
2Na
2The Mg molecular formula is calculated, near theoretical value.
Compound in structural formula I provided by the invention both can provide the energy for pathological tissues or organ cell by its negatively charged ion, can pass through Mg again
2+Regulate or participate in its biochemical functions, both synergies can reach the rational infringement of control tissue or organ cell's dysfunction and cytopathy thereof, are of value to its function of organized renewing.
The compounds of this invention, toxicity is little, and the preparation method is simple.The evidence of animal pharmacodynamics to coronary artery vasoconstriction model validation, can improve myocardial damage due to the coronary ischemia anoxic through antagonism hypophysis institute, and obvious function of resisting myocardial ischemia is arranged.Hypoxia-bearing capability under the bright raising mouse normal pressure of The compounds of this invention energy.Prove through rat test that in addition The compounds of this invention has obvious hypotensive effect.
Claims (3)
1. Compound D-fructose-1,6-diphosphate sodium U.S. is characterized in that having following structural formula:
2. method for preparing the described structural formula I of claim 1 compound, it is characterized in that adopting such step: at first 5～10% glucose, 6～8% phosphoric acid salt, 40～60% cereuisiae fermentum and excess water are prepared into mixing solutions, regulate pH value to 5～6, the fermented liquid that obtains through four hours continuous phosphorylation reactions of enzymatic, after removing yeast and protein, get supernatant liquor and adjust pH value to 8～9, discard precipitation, add CaCl
2Solution, the fructose diphosphate calcium raw product that must have a large amount of precipitations to produce, dissolution precipitation, discard insolubles, supernatant liquor is adjusted pH value to 8, and collecting precipitation gets fructose diphosphate calcium white powder after the drying, after its dissolving, make fructose diphosphate calcium change into structure I I formula fructose diphosphate by storng-acid cation exchange resin; With itself and magnesium oxide or the reaction of alkali formula magnesium salts, neutralize with it with sodium hydroxide again, add then in the ethanol, stir, centrifugal, treat precipitation produce after again with ethanol to its recrystallization, xln is carried out promptly getting compound in structural formula I after the drying at last.
3. the application of the described compound in structural formula I D-fructose-1,6-diphosphate of claim 1 sodium magnesium in preparation treatment myocardial ischemia medicine and antihypertensive drug.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98112218A CN1057299C (en) | 1998-08-28 | 1998-08-28 | Sodium magnesium D-fructose-1,6-diphosphate and its preparation method and application |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98112218A CN1057299C (en) | 1998-08-28 | 1998-08-28 | Sodium magnesium D-fructose-1,6-diphosphate and its preparation method and application |
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| Publication Number | Publication Date |
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| CN1211577A CN1211577A (en) | 1999-03-24 |
| CN1057299C true CN1057299C (en) | 2000-10-11 |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100408047C (en) * | 2005-08-31 | 2008-08-06 | 杨喜鸿 | Medicinal composition of fructose diphosphate sodium and magnesium salt |
| CN104497060A (en) * | 2014-12-26 | 2015-04-08 | 精晶药业股份有限公司 | Method for preparing sterile fructose diphosphate arginine salt |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1089655A (en) * | 1993-01-12 | 1994-07-20 | 中国人民解放军海军医学研究所 | The Fructose Diphosphate fermentation method for producing |
| CN1100726A (en) * | 1993-01-13 | 1995-03-29 | 韦斯卡玛生物工业化学药物合股公司 | New process for obtaining octahydro trisodium salt of fructose 1,6-diphosphate (FdPNa3H*8H2O) in crystalline form |
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1998
- 1998-08-28 CN CN98112218A patent/CN1057299C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1089655A (en) * | 1993-01-12 | 1994-07-20 | 中国人民解放军海军医学研究所 | The Fructose Diphosphate fermentation method for producing |
| CN1100726A (en) * | 1993-01-13 | 1995-03-29 | 韦斯卡玛生物工业化学药物合股公司 | New process for obtaining octahydro trisodium salt of fructose 1,6-diphosphate (FdPNa3H*8H2O) in crystalline form |
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| CN1211577A (en) | 1999-03-24 |
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