Latest ArticlesRoflumilast is a selective phosphodiesterase-4 inhibitor. Roflumilast 0.3% cream was approved by the U.S. FDA on July 29, 2022 (trade name Zoryve) for the treatment of plaque psoriasis in patients of 12 years or older, including intertriginous areas. Unlike other topical medicines, roflumilast has a higher safety profile, it is non-irritating to the skin, can be used continuously in long-term, and does not thin the skin. This article reviews its mechanism of action, pharmacokinetics, safety, clinical efficacy and precautions for use.
The U.S. Food and Drug Administration (FDA) has issued a series of policy documents in recent years to accelerate the approval and marketing of generic drugs. This article briefly introduced the relevant contents of one of these documents, i.e., "Good Abbreviated New Drug Application Assessment Practices", to explain how the US FDA tries to find a way, from the agency's perspective, to standardize the review process of generic drugs, and improve the review efficiency and effectiveness to promote generic drug marketing without quality compromising. Also, some thoughts were put forward respecting the relevant policies for the reform of China's drug review and approval system.
Ergosterol peroxide, a derivative of ergosterol, is widely found in a variety of medicinal fungi and plants and has various biological activities because of its 5α, 8α-peroxide bridge structure, such as anti-tumor, anti-virus, immune regulation, bacteriostasis and anti-inflammation. It is worth noting that the anti-tumor activity of ergosterol peroxide is significantly higher than ergosterol. At present, the preparation processes of ergosterol peroxide mainly include biological extraction and chemical synthesis. Biological extraction fails to acquire a large amount of ergosterol peroxide because of its low content in natural resources. However, chemical synthesis is convenient, and may realizes the industrialization of ergosterol peroxide. Here, the progress in study on biological activities and preparation of ergosterol peroxide was reviewed to provide direction for its application.
To evaluate the clinical safety and effectiveness of Jiuwei Zhike mixture in the treatment of wind-heat cough syndrome of acute bronchitis.
A randomized, double-blind, double-simulation, placebo and positive drug controlled, multi-center clinical trial design was adopted. The selected disease was acute bronchitis (wind-heat cough syndrome). Seven hundred subjects from 10 research centers were planned to be included and divided into treatment group, positive drug control group and placebo group in a ratio of 3∶1∶1. The patients took Jiuwei Zhike mixture+Jizhi syrup simulation agent, Jiuwei Zhike mixture simulation agent+Jizhi syrup, or Jiuwei Zhike mixture simulation agent+Jizhi syrup simulation agent for 7 d.
Jiuwei Zhike mixture took effect on acute bronchitis (wind-heat cough syndrome) from the 3rd day of administration. By the 7th day of administration, 54.7% of the subjects' cough symptoms completely disappeared (49.2% in the positive drug group and 15.1% in the placebo group), with a clinical recovery rate of about 51.6% (43.5% in the positive drug group and 13.7% in the placebo group), and a total effective rate of 93.4% (87.1% in the positive drug group and 41.9% in the placebo group). And it had a significant improvement effect on the symptoms of the disease.
Jiuwei Zhike mixture is safe and effective in treating acute bronchitis (wind-heat cough syndrome) and its curative effect is not inferior to Jizhi syrup and superior to placebo.
Targeted protein degradation (TPD) strategies have been used by academia and industry as one of the promising new drug development technologies to address targeted proteins that are not effectively acted upon by conventional small molecule inhibitors. Protein hydrolysis-targeted chimeras (PROTAC) have become the most well-studied protein-targeted degradation technique in TPD, which comprises of a POI-binding ligand, an E3 ligand, and a linker connecting the two ligands. Once the POI ligand binds to the receptor protein, PROTAC recruits the E3 ligand to ubiquitinate the protein and finally degrades it through the ubiquitin-proteasome system. PROTAC technology offers great potential for therapeutic applications because it can target proteins that lack well-defined active degradation sites, which are often involved in the pathogenesis of cancer and other diseases. To enhance PROTAC's target delivery and tissue selectivity, the industry has begun to investigate new strategies, such as discovering new E3 ligases and developing corresponding ligands, along with continuing to investigate more emerging PROTAC modalities to further promote PROTAC. These strategies and relevant studies are discussed in this review.
To optimize the preparation and solidification process of paeonol nanosuspensions.
Paeonol nanosuspensions was prepared by solvate-non-solvent precipitation method. With the appearance character, particle size and polymer dispersity index (PDI) as the evaluation indexes, the type of stabilizer, stirring time, stirring speed, drug-auxiliary ratio, organic phase-water ratio and water phase temperature as the influencing factors, the preparation process of nanosuspensions was optimized, and the stability of the prepared nanosuspensions was investigated. The freeze-drying method was used for solidification, and the effect of freeze-drying protectant on solidification was investigated. The drug loading, scanning electron microscopy, differential scanning calorimetry, X-ray diffraction and dissolution in vitro of the solidified nanosuspensions were characterized.
The preparation process of paeonol nanosuspensions was povidone K60 as stabilizer, drug-to-auxiliary ratio 1∶3, organic phase water ratio 1∶10, at 25 ℃, 400 r·min-1 magnetic stirring for 30 min. The prepared nanosuspensions had a particle size of about 40 nm, with narrow distribution and good stability. The lyophilized protectant was determined to be 5% trehalose. The drug loading capacity of solidified nanosuspensions was 21.63%, and the microscopic surface morphology was spherical, and the drug structure changed from crystalline form to amorphous form. The cumulative dissolution rate of the suspension reached 87.12% in 1 h.
The formulation and preparation process of paeonol nanosuspensions are simple, easy to operate, with good formability after solidification and fast dissolution, which lay a foundation for the development of more dosage forms.
Focusing on the specialty of locally applied locally acting drugs, we discuss and explain the special considerations in its design and evaluation of clinical trials.
The technical guidelines on the research and development of locally applied locally acting drugs issued by domestic and foreign regulatory agencies and related literature were extensively investigated. The relevant drug research and development situation and review practice were combed. Combined with case analysis and expert discussion opinions, the technical standards for clinical research and development of local drugs under different registration types were discussed.
The sponsor should formulate the corresponding research and development strategy based on the clinical medication needs and developmental background. For the innovative drugs, in addition to following the general consideration of clinical trials of innovative drugs, specific studies should also be carried out at the same time considering the characteristics of drug dosage forms, the routes of administration, and application sites, etc. Meanwhile, due to the technical and ethical difficulties of sampling in local pharmacokinetics and pharmacodynamics research, pharmaceutical quality research and comprehensive non-clinical research are particularly important. Some necessary exploratory and confirmatory clinical trials should be carried out combining the clinical data of the original active ingredient to prove the clinical advantages in safety and effectiveness etc. of the improved drug. For generic drugs that is locally administered and locally acting, beside pharmacy and non-clinical comparative studies with the original reference preparations, the sponsors may also need to carry out necessary human pharmacokinetics, pharmacodynamics, and even clinical equivalence trials to prove the consistency of quality and efficacy of generic drugs and reference preparations.
The study aims to prepare human immunoglobulin by chromatography combined with low-temperature ethanol, detect the effect of impurities removal in the preparation process and the effect of chromatography on product quality.
Human immunoglobulin (pH 4) was prepared by one-step anion-exchange chromatography from FII precipitated from healthy human plasma. It was further separated and purified by low-temperature ethanol-protein separation. The distribution of molecular size, IgA content, IgG content and IgG subclasses distribution, protein secondary structure of IgG were determined and analyzed. The effect of IgA and IgM removal of intravenous human immunoglobulin (pH 4) prepared by low-temperature ethanol protein separation and anion exchange purification was compared.
The precipitation of component II was dissolved by 5-fold volume of water for injection, and the dissolution rate of IgG was higher after stirring for 2 h. The content of IgA in intravenous human immunoglobulin (pH 4) prepared by anion exchange chromatography combined with low-temperature ethanol was controlled below 100 μg·mL-1, consistent with the distribution of molecular size and IgG isoforms of commercial products. The virus inactivation flux of nanofilms (20 nm) was increased.
Anion exchange chromatography can reduce the residual amount of IgA, IgM and other impurities in IVIG products, improve the permeability of nano-film (20 nm), and has no significant effect on the key quality of IVIG products.
Taking the development of dermatology drugs as an example, proposals are provided after analysis by summarizing the common clinical questions about drugs development encountered in communication, in order to provide reference for the same problems and improve the efficiency and quality in communication system.
The clinical improvement questions were collected and classified regarding dermatology drugs' communication applications in the communication subsystem of the Center for Drug Evaluation of National Medical Products Administration drug technical review system. The common questions were analyzed and regulatory considerations for improvement were elaborated.
Efficient communication system can promote the interaction between research and regulation, solve more individual problems, satisfy the needs in drug developments; however, developers and regulators need to work together to improve the quality and efficiency of communication.
To establish the method of simultaneous determination of 12 major chemical components (such as berberine, magnolflorine and curcumin) in Tibetan medicine Ji-Ni De-Xie.
The separation was achieved on a WondaSil C18-WR column. High performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QqQ-MS) was used with the mobile phase 0.1% formic acid solution (A)-methanol (B) under gradient elution. The temperature of Electron Spray Ionization (ESI) was 300 ℃. The charged ions were scanned in positive and negative ion modes at the same time with multiple reaction monitoring. The contents of 12 components in 5 batches of samples were calculated according to the linear equation of 12 reference substances.
The 12 components of the Ji-Ni De-Xie have a good linear relationship within the detection range. The average contents of magnolflorine, jatrorrhizine, berberine, curcumin, demethoxycurcumin, gallic acid, chebulagic acid, ferulic acid 4-O-β-D-glucopyranoside, hydroxysafflor yellow A, rutin, ferulic acid, and ellagic acid are 3.18, 0.20, 1.71, 0.52, 0.22, 15.93, 7.56, 3.29, 0.07, 0.20, 1.47, 2.89 mg·g-1, respectively.
The established analytical method is highly selective with high sensitivity. providing reference for the quality control of the Tibetan medicine Ji-Ni De-Xie.
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