ABSTRACT
In recent years, the number of clinical trials of stem cell products has increased, and the research and development technology and evaluation system have developed rapidly. Human pluripotent stem cell (hPSC)-derived cellular products are in the phase I/II stage of clinical trials. Related products include hPSC-derived neurons, retinal pigment epithelial cells, pancreatic beta cells, etc. They are generally used for the repair and replacement of functional cells related to degenerative diseases and genetic diseases via local transplantation. So far, no similar products have been officially approved on market. As hPSC possesses multi-directional differentiation potential and the ability to form teratoma in vivo, compared with other stem cell products, hPSC-derived cellular products have relatively higher risk of tumorigenicity, longer differentiation induction cycle, more complex production process, together with the rapidly updating quality characterization methods, which pose challenges to the scientific evaluation of their human applications. Based on the problems in the recent review and communication of clinical trial applications of stem cell products, and with reference to the relevant technical guidelines, this paper proposes the chemistry, manufacturing, and controls review considerations on the manufacturing process and quality study of hPSC-derived cellular products. We hope to improve the communications between developers and regulators.
ABSTRACT
Objective: The number of pharmacists regularly working at geriatric health service facilities is limited, but many users of such facilities have multiple chronic conditions and receive continuous pharmacotherapy, simultaneously using numerous different types of oral drugs. We examined the outcomes of pharmacotherapeutic intervention provided by hospital pharmacists for geriatric health service facility users.Methods: We examinedthe outcomes of active pharmacotherapeutic intervention providedby hospital pharmacists for 154 facility users.Results: After the intervention, there were significant decreases in the mean number of types and price of drugs used, as they decreased from 7.38 to 6.17 and 368.3 to 309.2 yen/day, respectively. The number of prescription drugs changed was 300, and 206 of these changes were proposedby the pharmacists. The efficacy-basedcategories that these drugs belongedto widely ranged. The most frequent reasons for change were the “disappearance of symptoms”, “based on indications”, and “suspected adverse events”. Adverse events variedfrom mildto those that may leadto severe conditions.Conclusion: Pharmacotherapeutic interventions by pharmacists may optimize pharmacotherapy, reduce polypharmacy, and reduce the financial burden on geriatric health service facilities.
ABSTRACT
Objective To determine the optimal model for the evaluation of pharmacodynamics of Fangji Huangqi Decoction. Methods By changing the doses and times of doxorubicin and the intervention of Fangji Huangqi Decoction and a series of test drugs, the effects of different doses and times of doxorubicin on the model were explored, and body weight, organism index, urine protein quantitation, renal histopathology results, and serum biochemistry can be regarded as evaluation indexes. Results For M1 (5 + 2) mg/kg model, the mortality rate of rats was higher. For M2 (6 mg/kg) model, the mortality rate was up to 20%, and the indicators reflecting renal function did not callback, but instead it showed much higher levels than the model group after receiving the test drug. For M3 (4 + 2) mg/kg model, the callback of part of the indexes, such as lung and kidney organ index, serum total triglyceride, and total protein levels, occurred after receiving the test drug, but the curative effect is not ideal. For M4 or M4’ (4 + 1) mg/kg model, the quantitative level of urinary protein in model rats was significantly different from that in the control at the 14th d, and the sustained and stable growth trend was observed; Moreover, the indicators mentioned above have different degrees of callback with high-, middle-, and low dose of Fangji Huangqi Decoction. Conclusion The final model weight of the rats was determined to be about 300 g, and the cumulative dose of doxorubicin was 5 mg/kg tail intravenous injection of doxorubicin was adopted as follows: on the 1st d of the experiment, 4 mg/kg doxorubicin was injected, and followed another 1 mg/kg at intervals of 1 week, which was the best way to evaluate the pharmacological effect of the related drugs derived from the Fangji Huangqi Decoction and the middle dose was the best.