Formulations for microparticle delivery of zinc protoporphyrins
A technology of microparticles and stabilizers, applied in the field of preparations for the delivery of zinc protoporphyrin by microparticles, which can solve problems such as difficulties in compound delivery
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Embodiment 1
[0075] Effects of light on metalloporphyrin-treated neonatal mice
[0076] Neonatal hyperbilirubinemia arises from an imbalance between bilirubin production and its clearance. A study of aggressive and conservative phototherapy in very low birth weight (ELBM) infants showed only a significant reduction in the rate of neurodevelopmental impairment (NDI) with aggressive phototherapy, but this reduction was augmented by increased mortality in infants ≤501–750 g rate is offset. Furthermore, photooxidation of light, including blue light, has been shown in animals. In addition, it has also been suggested that lower hemoglobin levels in ELBW infants may put them at higher risk of phototoxicity because less light is absorbed by circulating hemoglobin. Metalloporphyrins (Mp) are promising drugs for the treatment of hyperbilirubinemia, but most of them are photosensitizing and thus potentially phototoxic. Zinc protoporphyrin (ZnPP) is a promising Mp with sufficient potency but poor s...
Embodiment 2
[0093] preparation
[0094] One disadvantage of ZnPP is that it is not orally bioavailable and it requires parenteral administration. The low oral bioavailability of ZnPP is due to its low solubility and chemical instability in low pH environments, such as seen in the stomach, and low aqueous solubility at neutral pH, which limits the dissolution of ZnPP and subsequent intestinal Absorption in the tract. ZnPP reacts in low pH aqueous solution to form protoporphyrin IX free acid, which cannot inhibit HO.
[0095] There is a need for a formulation that increases the oral bioavailability and effectiveness of ZnPP by protecting the molecule from interaction with the acidic environment found in the stomach and increasing its water solubility at neutral pH to facilitate absorption in the upper small intestine. Ideally, the formulation is a solid state in powder form to improve the shelf life of the final pharmaceutical dosage form and its manufacturability.
[0096] The micropart...
Embodiment 3
[0111] Preparation of spray-dried powders with higher ZnPP content
[0112] has a lower The ZnPP preparation of content; Preparation composition:
[0113] ZnPP; 20% w / w
[0114] DPPC; 42%w / w
[0115] L100-55; 38% w / w
[0116] Preparation of 1% solids (w / v) stock solution for spray drying: ZnPP was sonicated in 1M ammonium hydroxide (constituting 12.5% of total solvent volume). DPPC dissolved in ethanol (50% of total solvent volume) was added. added in ethanol L100-55 (37.5% solvent volume remaining). Spray drying conditions: same as above.
[0117] Observe the preparation, as Figure 7B Shown: 20% ZnPP content confirmed by LCMS. Although there was some release of ZnPP in 0.1 N HCl medium, washing and resuspension of the acid-exposed particles in PBS pH 7.4 buffer resulted in a substantial release of ZnPP as measured by HPLC / MS. SEM images show that these 38% w / w Granules compared to previously determined formulations (75% w / w ) have a similar shape. The wr...
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