Preclinical trials of human erythrocyte superoxide dismutase injection

To assess the quality of human erythrocyte superoxide dismutase (SOD) injection reaching the official standard for its clinical uses Methods Human erythrocyte SOD injection prepared by McCord Fridovich's method without column chromatography but with some modifications was used in preclinical trials, to observe the general pharmacology and pharmacodynamics of the product Results The quality of human erythrocyte SOD injection conformed to the official standard of a biological product, which was found to be non toxic and did not have any effects on the central and autonomic nervous systems as well as cardiovascular and respiratory systems The efficacy of anti inflammation and promotion of immuno regulation especially on carrageenan and adjuvant induced polyarthritis were shown in animals Conclusion Human erythrocyte SOD injection is appropriate for prophylactic and therapeutic uses in clinical trials

Pilot-Scale Production of Lyophilized Inactivated Rabies Vaccine Candidate in Vero Cells under Fully Animal Component-Free Conditions Using Microcarrier Technology and Laboratory Animal Trials

The upstream process was carried out in an animal component-free medium on Cytodex 1 microcarriers. Recombinant trypsin is a non-animal derived protease used as an alternative to animal-derived trypsin. To inactivate recombinant trypsin, a soybean trypsin inhibitor (STI) should be added to the medium. A protocol was first tested in T-flasks and then passaged to 500 mL and 3 L spinner flasks. Cell detachment was completed in 10 - 12 min, and 0.4 g/L STI was added to a 3L spinner, and cells were transferred into a 30 L stirred tank bioreactor. On day 5, the cell density had reached its maximum (around 1.8 × 106 cells/mL). At an MOI of 0.3 with serum-free medium conditions, cell infection yielded a maximal rabies virus titer of 1.82 × 107 FFU/mL at 5 days. All cell culture conditions and virus growth kinetics in serum-free media were investigated. In conclusion, Vero cells were grown on Cytodex 1 with serum-free media and a high amount of rabies virus was obtained. A mouse challenge was used to determine the immune response to an inactivated rabies virus vaccine candidate. Also, we evaluated inactive rabies vaccine candidate safety, and immunogenicity in mice, sheep, horses, and cattle. We found that no horses, sheep, or cattle who were given vaccine IM at 3.2 IU/dose exhibited any clinical sign of disease and all developed high VNA titers (up to 10.03 IU/mL) by 3 - 4 WPI. After the accelerated stability studies, the lyophilized inactivated rabies vaccine candidate showed enough antigenic potency (2.6 IU/mL) in the mouse challenge test. Also, 18-month long-term stability studies showed enough immune response (1.93 IU/mL) on day 14. The activity of the vaccine candidate showed a good immune response and safety criteria that meet WHO requirements. This is the first pilot-scale mammalian cell-based viral rabies vaccine production study in Türkiye that used microcarriers.

Research and Development of the Effective Components of Panaxdiol Saponin as New Chinese Patent Medicine for Treating Hemocytopenia

Pancytopenia （hemocytopenia） such as primary immune thrombocytopenia （ITP）, aplastic anemia and chronic neutropenia （agnogenic leukocytopenia） were often treated by glucocorticoids, androgen and immunosuppressive agents at present, but the response to these treatments has not been always satisfactory, and may cause serious adverse events. Our research has identified a biological active component in ginseng extract and the active component, panaxadiol saponins component （PDS-C）, was isolated from total saponins of ginsenosides, and formulated into capsules named as Painengda （派能达）. We successfully obtained approval from State Food and Drug Administration （SFDA） of China in 2010 to conduct clinical trials of PDS-C as class-five new Chinese patent medicine. Phase Ⅰand phase Ⅱ clinical trials of PDS-C and Painengda Capsule were carried out in the treatment of ITP and agnogenic leukocytopenia. Thecomposition and content of PDS-C have been analyzed and defined by high-performance liquid chromatography mass spectrometry （HPLC-MS） and HPLC using specific monomers of ginsenosides as the reference standards. PDS-C is very efficacious for treating mice and rats with ITP and aplastic anemia, and myelosuppression caused by chemotherapy or radiation. Our animal model studies and cell biology and molecular biology experiments demonstrated that PDS-C possessed dual activities, namely that of promoting proliferation and differentiation of hematopoietic progenitor cells, and that of regulating the immune function. PDS-C and Painengda Capsule as a new Chinese patent medicine have been successfully transferred to industry. We believe that PDS-C is effective and safe in the treatment of refractory hemocytopenia. The advantages are that it is effective in small doses, it is convenient to use because of its oral administration, its lack of adverse events, it could be used alone or in combination with pharmacological agents, which improve the efficacy and decrease adverse events.