Effective Increase of Serum Vitamin D3 by IV Application of a Cholecalciferol-N-Acetyl-Galactosamine-Stabilized Dimer: a Clinical Murine Trial Study

BACKGROUND: Pre-clinical toxicology studies of human Gc-protein (vitamin D binding protein) are of special interest as to the transport of vitamin D and its biological activities. We have demonstrated that the oral application of a special dimeric vitamin D complex reduces oxidative stress and increases the quality of life in autistic children. Therefore, safety and toxic effects of two dimeric cholecalciferol-N-acetyl-galactosamine-albumin complexes were evaluated in increasing intravenous (iv.) vitamin D levels administered in a pre-clinical trial in mice over a 5-week period. METHODS: Over a period of 5 weeks, two times a week, mice received iv. administration of one of the following: (a) 1.2 IE of vitamin D-N-acetyl-galactosamine-albumin (Vitamin D3 NAGA, ImmunoD(R) group), (b) 1.2 IE of vitamin-D-poly-N-acetyl-galactosamine-albumin (Poly-Nac group), or (c) isotonic saline solution (sham group). Before and after the trial, red and white blood cell panels (RBS, WBC and platelets) were determined. Furthermore, vitamin D levels, electrolytes, and C-reactive protein levels were measured directly before sacrificing. RESULTS: No toxic effects were observed during iv. injection with dimeric vitamin D complexes, neither in the sham group, nor in the two treatment groups. Vitamin D levels increased significantly within 5 weeks in the Poly-Nac group (26.6 +/- 8.8 ng/mL; p = 0.001) compared to the sham group (3.1 +/- 0.9 ng/mL), and the Poly-Nac group to the ImmunoD group (7.0 +/- 3.6 ng/mL; p = 0.003). A significant increase of vitamin D was also obtained in favor of the ImmunoD group compared to the sham (p = 0.03). Electrolytes (K, Na, Cl, Mg, Ca) and C-reactive protein showed no significant differences after administration in all three mice groups. Also, no significant differences were observed between these three groups in the WBC and RBC blood panels. CONCLUSIONS: The two dimeric vitamin D complexes used in this pre-clinical study showed no side or toxic effects after iv. administration in mice, but a sole increase in vitamin D levels without any change in electrolytes or blood cells. Therefore, we assume this newly developed composition to be safe in oral or iv.-administration and further pre-clinical studies can be conducted to evaluate the value in treatment of various diseases related to vitamin D deficiencies

The hypolipidemic natural product Commiphora mukul and its component guggulsterone inhibit oxidative modification of LDL.

There is accumulating evidence that LDL oxidation is essential for atherogenesis, and that antioxidants that prevent this oxidation may either slow down or prevent atherogenesis. In the present study, we found that Commiphora mukul and its cholesterol-lowering component, guggulsterone, effectively inhibited LDL oxidation mediated by either catalytic copper ions, free radicals generated with the azo compound 2,2\u27-azobis-(2-amidinopropane)dihydrochloride (AAPH), soybean lipoxygenase enzymatically, or mouse peritoneal macrophages. This inhibition was assessed by the decrease in the following parameters describing LDL oxidation: conjugated dienes, relative electrophoretic mobility (REM), thiobarbituric acid reactive substances, lipid hydroperoxides, oxidation-specific immune epitopes as detected with a monoclonal antibody against oxidized LDL, and the accumulation of LDL derived cholesterol esters in mouse peritoneal macrophages. We concluded that C. mukul and its lipid-lowering component, guggulsterone, significantly inhibit LDL oxidation. The combination of antioxidant and lipid-lowering properties of C. mukul and guggulsterone makes them especially beneficial against atherogenesis

Method development and validation for the analysis of a new anti-cancer infusion solution via HPLC

A fast and simple HPLC method has been developed and validated for the quantification of a completely new anti-cancer drug during the manufacturing process. The combination of four compounds including alpha-ketoglutaric acid, hydroxymethylfurfural, N-acetyl-L-methionine and N-acetyl-L-selenomethionine, administered intravenously, is still in test phase but has already shown promising results in cancer therapy. HPLC separation was achieved on an RP-18 column with a gradient system. However, the highly different concentrations of the compounds required a variation in the detection wavelength within one run. In order to produce a chromatogram where peaks were comparable on a similar range scale, detection at absorption maxima for the two most concentrated components was avoided. After optimization of the gradient program it was possible to detect all four substances within 14 min in spite of their strongly different chemical structure. The method developed was validated for accuracy, repeatability, reproducibility and robustness in relation to temperature and pH of buffer. Linearity as well as the limit of detection and quantification were determined. This HPLC method was found to be precise, accurate and reproducible and can be easily used for in-line process control during the manufacture of the anti-tumour infusion solution