The objective of this experiment was to determine the effect of supplementation of hot melt extrusion (HME) processed Zn sulfate on growth performance, nutrients digestibility, small intestinal morphology and excretion of Zn in weanling pigs. A total of 200 piglets of mixed sex randomly allotted to four treatments on the basis of initial BW (7.15±0.81 kg). There were five replicates in each treatment with 10 pigs per replicate. The experimental treatments consisted of: 1) basal diet containing ZnSO4; 2) basal diet containing Zn-Methionine (ZnMet); 3) basal diet containing low level of nano-Zn as HME (ZnHME50); 4) basal diet containing medium level of nano-Zn as HME ZnSO4 (Zn-HME75). The average daily gain was improved by the ZnMet and ZnHME75 compared with the pigs fed ZnSO4 supplemented diets (p=0.009). Moreover, ZnHME75 and ZnMet affected on the ATTD of CP during phase 2 (p=0.014). The villus height (VH) was affected by increasing when pigs fed diets supplemented the ZnHME75 (P=0.044). The pigs fed diets supplemented ZnHME50 had significantly the lowest (p=0.037) Zn content in liver compared with other treatments. The Zn content in the feces was significantly higher (p<0.001) in ZnSO4 and ZnMet compared with ZnHME50 or ZnHME75. In conclusion, it could be concluded that dietary Zn can be reduced by 25% with ZnHME without any detrimental effect on performance of weanling pigs.

Background: The objective of this study was to make colloidal dispersions of the active compounds of radix of Angelica gigas Nakai that could be charaterized as nano-composites using hot melt extrusion (HME). Food grade hydrophilic polymer matrices were used to disperse these compound in aqueous media. Methods and Results: Extrudate solid formulations (ESFs) mediated by various HPMCs (hydroxypropyl methylcelluloses) and Na-Alg polymers made from ultrafine powder of the radix of Angelica gigas Nakai were developed through a physical crosslink method (HME) using an ionization agent (treatment with acetic acid) and different food grade polymers [HPMCs, such as HP55, CN40H, AN6 and sodium alignate (Na-Alg)]. X-ray powder diffraction (XRD) analysis confirmed the amorphization of crystal compounds in the HP55-mediated extrudate solid formulation (HP55-ESF). Differential scanning calorimetry (DSC) analysis indicated a lower enthalpy (ΔH = 10.62 J/g) of glass transition temperature (Tg) in the HP55-ESF than in the other formulations. Infrared fourier transform spectroscopy (FT-IR) revealed that new functional groups were produced in the HP55-ESF. The content of phenolic compounds, flavonoid (including decursin and decursinol angelate) content, and antioxidant activity increased by 5, 10, and 2 times in the HP55-ESF, respectively. The production of water soluble (61.5%) nano-sized (323 ㎚) particles was achieved in the HP55-ESF. Conclusions: Nano-composites were developed herein utilizing melt-extruded solid dispersion technology, including food grade polymer enhanced nano dispersion (< 500 ㎚) of active compounds from the radix of Angelica gigas Nakai with enhanced solubility and bioavailability. These nano-composites of the radix of Angelica gigas Nakai can be developed and marketed as products with high therapeutic performance.

Background : The objective of this study was to make colloidal dispersion of the active compound was characterized nano-composite from radix of Angelica gigas Nakai using hot melt extrusion (HME). Therefore, food grade hydrophilic polymer matrices was used to disperse compound in aqueous media. Methods and Results : Extrudate solid formulations (ESFs) mediated various HPMCs (hydroxypropyl methylcellulose) and Na-Alg polymer from ultrafine powder of radix of Angelica gigas Nakai was developed through physical crosslink method (HME) with ionization agent (treatment of acetic acid) and food grade polymer [HPMCs such as HP55, CN40H, AN6 and sodium alignate (Na-Alg)]. X-ray powder diffraction (XRD) analysis confirmed the amorphization of crystal compounds in extrudate solid formulations mediated HP55 (HP55-ESF). Differential scanning calorimetry (DSC) analysis indicated a lower enthalpy (ΔH = 10.62 J/g) of glass transition temperature (Tg) in HP55-ESF. Infrared fourier transform spectroscopy (FT-IR) reveled new functional groups produced in HP55-ESF. Phenolic compound, flavonoid (including decursin and decursinol angelate) and antioxidant activity increased at 5, 10 and 2 times in HP55-ESF. Water solubility (61.5%) nano size (323 ㎚) particle was achieved in the HP55-ESF. Conclusion : Nano-composites have been developed utilizing melt-extruded solid dispersions technology by food grade polymer enhanced nano dispersion (< 500 ㎚) of active compound from radix of Angelica gigas Nakai with enhanced solubility and bioavailability. This nano-composites of radix of Angelica gigas Nakai developmental and marketed products to enable therapeutic performance.

Background : The root of Angelica gigas Nakai is used as a traditional herbal medicine in Korea for the treatment of many diseases. Poor water solubility of the active compounds from A. gigas Nakai is a major obstacle to bioavailability. Methods and Results : This work aimed to enhance the solubility of active compounds by a chemical (viz. surfactant) and physical (HME, hot melt extrusion) crosslinking method (CPC) in A. gigas Nakai. Infrared fourier transform spectroscopy (FT-IR) revealed multiple peaks in extrudate solids representing new functional groups including carboxylic acid, alkynes and benzene derivatives. Differential scanning calorimetry (DSC) analysis of the extrudate showed lower glass transition temperature (Tg) and lower enthalpy (ΔH) [Tg: 43℃; ΔH: <6 (J/g)] compared to the non-extrudate (Tg 68.5℃; ΔH: 123.2) formulations. X-ray powder diffraction (XRD) analysis revealed amorphization of crystal materials in extrudate solid. In addition, enhanced solubility (53%), nanonization (403 ㎚), and higher amount of extracted phenolic compounds were achieved in the extrudate solid compared to non extrudate (36%, 1499 ㎚, respectively). Among the different extrudates, acetic acid and span 80 mediated formulations showed superior extractions efficiency. Conclusion : We conclude that the HME successfully enhanced the production of amorphous nano dispersions of phenolic compound including decursin from extrudate solid formulations. human dermal fibroblasts, which is, associated with the regulation of procollagen biosynthesis resulting from AMRP-induced TGF-β1 expression and the mitogenic activity in HDF cells, and therefore, is expected to reduce the age-dependent loss of extracellular matrix proteins.

Background: The root of Angelica gigas Nakai is used as a traditional herbal medicine in Korea for the treatment of many diseases. However, the poor water solubility of the active components in A. gigas Nakai is a major obstacle to its bioavailability. Methods and Results: This work aimed at enhancing the solubility of the active compounds of A. gigas Nakai by a chemical (using a surfactant) and physical (hot melt extrusion, HME) crosslinking method. Fourier transform infrared spectroscopy revealed multiple peaks in the case of the extrudate solids, attributable to new functional groups including carboxylic acid, alkynes, and benzene derivatives. Differential scanning calorimetry analysis showed that the extrudate soilid had a lower glass transition temperature (Tg) and enthalpy (ΔH) (Tg : 43℃, ΔH : < 6 J/g) as compared to the non-extrudate (Tg : 68.5℃, ΔH : 123.2) formulations. X-ray powder diffraction analysis revealed the amorphization of crystalline materials in the extrudate solid. In addition, enhanced solubility (53%), nanonization (403 ㎚), and a higher amount of extracted phenolic compounds were achieved in the extrudate solid than in the non-extrudate (solubility : 36%, nanonization : 1,499 ㎚) formulation. Among the different extrudates, acetic acid and span 80 mediated formulations showed superior extractions efficiency. Conclusions: HME successfully enhanced the production of amorphous nano dispersions of phenolic compound including decursin from extrudate solid formulations.

Background : Zinc (Zn) is one of dietary micronutrients and it is second highest trace element in the body. Over 95% of Zn is located in the cells, but its dominant storage site is absent in the body. Deficiency of Zn may result in anorexia, dysgeusia, dysosmia, skin rash, infection, alopecia, growth failure, and impaired wound healing. Therefore, adequate supplementation of Zn is very important to maintain normal physiological conditions. Methods and Results : Zinc sulfate monohydrate (ZnSO4)-loaded nanocomposites (NCs) were fabricated by using a hot-melt extruder (HME) system. Soluplus (SP) was adopted as an amphiphilic polymer matrix for HME processing. The micro-size of ZnSO4 dispersion was reduced to nano-size by HME processing with the use of SP. ZnSO4 could be homogeneously dispersed in SP through HME processing. ZnSO4/SP NCs with a 75 ㎚ mean diameter, a 0.1 polydispersity index, and a -1 mV zeta potential value were prepared. The physicochemical properties of ZnSO4/SP NCs and the existence of SP in ZnSO4/SP NCs were further investigated by solid-state studies. Nano-size range of ZnSO4/SP NC dispersion was maintained in the simulated gastrointestinal environments (pH 1.2 and 6.8 media). No severe toxicity in intestinal epithelium after oral administration of ZnSO4/SP NCs (at 100 ㎎/㎏ dose of ZnSO4, single dosing) was observed in rats. Conclusion : These results imply that developed ZnSO4/SP NC can be used as a promising nano-sized zinc supplement formulation. In addition, developed HME technology can be widely applied to fabricate nano formulations of inorganic materials.

Background : Cu ion is an essential mineral of animal feed. But rapid degradation of Cu ion in animal intestine causes poor immune activity and potential environment hazard. Therefore, to enhance immune system and control metal ion deliverly in intestine, we developed Cu ion nano suspension. In animal feed, > 127 ㎎/g of Cu ion are found but only 5 - 7 ㎎ are used out of them. Therefore, huge loss of Cu ion causes environment, economy and animal health problem. Methods and Results : Seven formulation were prepared to prepare nano suspension (particle size < 200 ㎚) of CuSO4. The particle diameter, polydispersity index, and zeta potential values of the samples were measured using dynamic light scattering (DLS) and laser Doppler methods (ELS-Z1000; Otsuka Electronics, Tokyo, Japan). Absorbance and Cu ion concentration was measured using UV-VIS Spectrophotometer. Cu ion nano particle (< 200 ㎚) was found in a formulation comprised of Cu ion : surfactant (lipophilic : hydrophilic) and PEG. In consistence with this result, total absorbance and concentration was found higher in the same formulation compared to control. Conclusion : From our experiment we may conclude that mixture of Cu ion : surfactant (lipophilic : hydrophilic) and PEG successfully prepared nano suspension which slow down the degradation of Cu ion in intestine with improving feed quality, animal health and prevent potential environment pollution.

Background : Angelica gigas is a biennial or short lived perennial plant found in China, Japan, and Korea. The root of Angelica gigas has been used in oriental traditional medicine and is marketed as a functional food product in Europe and North America. Cham-Dang-Gui (Korean Angelica, the dried root of Angelica gigas Nakai (AGN)) has been principally cultivated in Korea and used as a Korean medicinal herb. It contains several chemicals, such as pyranocoumarins, essential oils, and polyacetylenes. Methods and Results : Fresh Angelica gigas Nakai was purchased from Pyeongchang (Korea). Standard samples of D, DA were obtained from Korea Promotion Institute for Traditional Medicine Industry (Gyeongsan, Korea). Soluplus was purchased from BASF (Ludwigshafen, Germany). AGN was dried in the oven at 55°C for 24 h and cooled at room temperature. The AGN sample was then stored at 4°C until milling. Oral solid formulations based on Angelica gigas Nakai and Soluplus were prepared by the hot melt extrusion (HME) method. AGN was pulverized into coarse and ultrafine particles, and their particle size and morphology were investigated. Ultrafine AGN particles were used in the HME process with high shear to produce AGN-based formulations. In simulated gastrointestinal fluids (pH 1.2 and pH 6.8) and water, significantly higher amounts of the major active components of AGN, decursin (D) and decursinol angelate (DA), were extracted from the HME-processed AGN/Soluplus group than the AGN EtOH extract group (p < 0.05). Based on an in vivo pharmacokinetic study in rats, the relative oral bioavailability of decursinol (DOH), a hepatic metabolite of D and DA, in administered mice was 8.75-fold higher than in AGN EtOH ext-treated group. Conclusion : Soluplus-included solid formulation prepared by HME can be a promising carrier for oral delivery of phytochemicals. These findings suggest that HME-processed AGN/Soluplus formulation could be a promising therapeutic candidate for oral bioavailability.