Huahai Pharmaceutical (China)

To probe the formation mechanism of N-despropyl ropinirole, an oxidative degradant in ropinirole hydrochloride extended-release tablets. Forced degradation studies were employed to investigate the mechanism by treating ropinirole API with H2O2 and AIBN, respectively, and the samples analyzed by high resolution LC-QTOF-MS. Meanwhile, the samples from the forced degradation of the extended-release tablets were analyzed by GC-QTOF-MS. The proposed mechanism was supported by an H218O isotope experiment. Lastly, API-excipient compatibility studies were conducted to evaluate the impact of the excipients on the formation of N-despropyl ropinirole. The growth trend of N-despropyl ropinirole in the accelerated stability study was similar to that observed in the forced degradation of ropinirole hydrochloride treated with AIBN, but vastly different from that observed in the forced degradation with H2O2. The forced degradation using isotope labelled H218O showed that 18O was incorporated into propionaldehyde, the volatile co-degradant in the formation of N-despropyl ropinirole. The API-excipient compatibility studies indicated that N-despropyl ropinirole was formed gradually in the presence of CMC-Na and HPMC, respectively. Degradation of ropinirole in the ropinirole hydrochloride extended-release tablets is most likely to proceed via a free radical-mediated oxidative pathway, rather than a nucleophilic oxidative pathway. The forced degradation experiment using H218O is consistent with the proposed free radical-mediated degradation mechanism. The source of the free radicals seems to originate from the two excipients, CMC-Na and HPMC. The results obtained in the current study would be quite beneficial for further improvement of the drug product in terms of controlling its major degradation pathway.

Herein, we report a concise and efficient one-pot total synthesis of TMC-205 in 77% overall yield (gram-scale) using only two simple and streamlined steps. In the proposed approach, a novel Heck-dehydration reaction and a practical aromatic carboxylic acid introduction strategy are reported, which are characterized by high atom economy, excellent regioselectivity and stereoselectivity (E-isomer). This synthesis protocol is protecting group-free, redox neutral, environmentally benign, and features simple operation steps. Through the implementation of this new, efficient and scalable synthesis method, the formal synthesis of a series of novel meroterpenoid natural products can be successfully realized. Moreover, the synthetic strategy and methodologies demonstrated in this paper are useful and can be easily extended to the preparation of other related biologically active molecules.

Antibiotic resistance is a major public health concern. Although novel antibiotic techniques are now in progress, immunotherapy is an unconventional and efficient approach to against resistant pathogens. Herein, an integrated microneedle patch (ANMN)

Organic fertilization has gained significant attention in horticulture as a sustainable alternative to conventional fertilization methods. Kiwifruit, a globally important crop, presents a unique opportunity to evaluate the impact of organic fertilization on both productivity and quality. This study examines various organic fertilizers used in kiwifruit cultivation, their application methods, and the influence on soil health and nutrient composition. Our analysis focuses on yield performance under organic fertilization, long-term effects on soil fertility, and a comparison with conventional practices. Additionally, the study explores how organic fertilization affects kiwifruit quality, including fruit size, nutritional content, taste, and post-harvest shelf life. Environmental benefits, such as reduced chemical inputs and enhanced sustainability, are highlighted alongside the economic advantages of organic kiwifruit in the market. Challenges, such as lower initial yields and regulatory issues, are discussed, with a case study demonstrating real-world applications. The study concludes by identifying research gaps and emphasizing the need for long-term studies and innovations in organic fertilizer development. Future directions focus on integrating organic practices with precision agriculture for improved productivity and sustainability.

Ulcerative colitis (UC) is an inflammatory bowel disease generally characterized by chronic, persistent, recurrent, and non-specific ulcers of the intestine. Its main clinical manifestations include abdominal pain, diarrhea, and bloody stools. This disease is difficult to cure and even carries the risk of canceration. It has been listed as a modern refractory disease by the World Health Organization. Though a large amount of drugs are available for the inhibition of UC, the conventional treatment such as aminosalicylic acids, glucocorticoids, immunosuppressors, and biological agents possess certain limitations and serious side effects. Therefore, it is urgently needed for safe and effective drugs of UC, and natural-derived flavonols and flavanones showed tremendous potential. The present study concentrated on the progress of natural-derived flavonols and flavanones from edible and pharmaceutical plants for the remedy of UC over the last two decades. The potential pharmaceutical of natural-derived flavonols and flavanones against UC were closely connected with the modulation of gut microflora, gut barrier function, inflammatory reactions, oxidative stress, and apoptosis. The excellent efficacy and safety of natural flavonols and flavanones make them prospective drug candidates for UC suppression.

Pulmonary arterial hypertension (PAH) is a serious disease with reduced systemic circulation and low bioavailability associated with conventional and dosed therapy, which inhaled drugs can avoid. A mean pulmonary artery pressure (mPAP) of ≥25 mmHg (1 mmHg = 0.133 kPa) at rest or ≥30 mmHg during exercise and a pulmonary capillary pressure or left atrial pressure (PLA) of ≤15 mmHg can be diagnosed with PAH. Pulmonary hypertension is classified into primary PAH and secondary PAH according to the presence or absence of principles or risk factors. The main symptoms of pulmonary hypertension include dyspnoea, syncope, weakness, chest pain, and the presence of varying degrees of peripheral oedema. It is a highly pathogenic and life-threatening disease and can lead to delays in treatment if not diagnosed in time. In the past few years, the studies related to this progressed slowly, which brought great harm to patients with PAH. Reports showed that patients diagnosed with PAH should receive routine preventative care, such as pneumococcal and influenza vaccinations. Inhalation therapy is mainly used for the treatment of respiratory diseases and is of great interest due to the concentration of the drug in the airways and lung tissues. Therefore, the present situation of pulmonary hypertension and the characteristics of inhalation preparation were reviewed in this paper to provide some related cue for the treatment of pulmonary hypertension. In the future, it is necessary to develop more treatment methods for pulmonary hypertension.

In October 2021, an India-based pharmaceutical company withdrew a number of batches of irbesartan and irbesartan hydrochlorothiazide finished products from the US market, due to the presence of unacceptable level of the “probably carcinogenic” nitrosamine “N-nitrosoirbesartan”. Nevertheless, there is no revealing of the exact structure of this so called “N-nitrosoirbesartan”. In the current study, we performed a set of 10 reactions of irbesartan with nitrous acid under various conditions and found no trace of this “N-nitrosoirbesartan” by a sensitive and accurate LC-MS method with limit of detection (LOD) of 30 ppb. With the use of LC-PDA/UV-high resolution MSn as well as 1D/2D NMR, the reaction products formed are found to be the two isomeric oxime derivatives of irbesartan, with the Z-isomer as the predominant product. Furthermore, no trace of this “N-nitrosoirbesartan” can be detected in representative commercial batches of irbesartan. Despite of the fact that in silico evaluation suggests that the two irbesartan oximes may be controlled as regular impurities, analysis of representative irbesartan commercial batches by the LC-MS method indicates that the oximes are not detected (LOD: 30 ppb).