Crystal of dibutyryl adenosine cyclophosphate calcium salt

Abstract

The invention relates to a crystal of a dibutyryl adenosine cyclophosphate calcium salt, the structural formula of the crystal is C72H92Ca2N20O32P4.9H2O, belongs to an orthorhombic crystal system anda P212121 space group, the cell parameters are shown in the description, alpha=beta=gamma=90 degrees, Z=4, the cell volume V is shown in the description , R=0.07, the true density of the crystal is 1.455 kg / m<3>, each cell comprises four minimal asymmetric units, and each minimal asymmetric unit further comprises 4 dibutyacyl adenosine cyclphosphate anions, 2 calcium ions, and 9 crystal water. Thestacking density of the crystal powder is more than 0.35 g / mL, the tap density is more than 0.38 g / mL, and the HPLC purity is more than 99.2%.

Description

technical field [0001] The invention belongs to the refining field of medicine and feed additives, and specifically relates to a crystal structure of dibutyryl cyclic adenosine phosphate calcium salt, a crystalline powder of dibutyryl cyclic adenosine phosphate calcium salt, and a preparation method thereof. Background technique [0002] Calcium Dibutyacyladenosine Cyclophosphate (DbcAMPCa), scientific name N 6 , 2′-O-Dibutyryladenosine-3′, 5′-cyclic monophosphoric acid, calcium, the molecular structure formula of its monovalent anion is attached figure 1 , is a derivative of cyclic adenosine monophosphate (cAMP), because it has better cell membrane permeability than cyclic adenosine monophosphate, and can resist the hydrolysis of phosphodiesterase in vivo, so its action time and speed are longer than cAMP And quickly, because it has significant effects in the treatment of heart disease, immune diseases, etc. (CN101172112A). [0003] The current preparation methods basical...

AI Technical Summary

Problems solved by technology

Although these several methods can improve the HPLC purity to more than 90%, there are several problems, either the cost is high, and it is not suitable for large-scale production; The particle size is too poor, the bulk density is small, and the stability is poor; in most cases, the above three problems exist at the same time

[0005] Due to technical limitations, the current domestic standard for dibutyryl cyclic adenosine monophosphate calcium salt is still "Chemical Drug Landmark Upgrade National Standard Volume 9", the version is relatively old, and the standard for product specifications is relatively low - "calculated as dry product, containing C18H23N5O8P 1 / 2Ca must not be less than 80.0%, light yellow powder, with special odor and hygroscopicity", but for medicine, the problem of impurities and particles is the bottleneck hindering the development of high-end

[0006] On the other hand, although the report on the structure of calcium dibutyryl cyclic adenosine monophosphate suggests that it can contain 0 to 2.5 crystal waters, the patent CN104478979A provides a powder X-ray diffraction pattern of the non-crystalline crystal form, but None of them can give its thorough three-dimensional structure information from the molecular level, and the amorphous products and non-crystalline water products are easy to absorb moisture and have instability compared with dibutyryl cyclic adenosine monophosphate calcium salt crystal products containing crystal water

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