We report the crystal structures of three matrine derivatives, namely, the salts (1R,2R,9S,17S)-6-oxo-7,13-diazatetracyclo[7.7.1.02,7.013,17]heptadecan-13-ium (2E)-3-(3,4-dihydroxyphenyl)prop-2-enoate (matrine caffeinate) sesquihydrate, C15H25N2O+·C9H7O4-·1.5H2O (Matrine-CA), and the 2-hydroxybenzoate (salicylate) monohydrate, C15H25N2O+·C7H5O3-·H2O (Matrine-SA), as well as the 1.75-hydrate form, (1R,2R,9S,17S)-7,13-diazatetracyclo[7.7.1.02,7.013,17]heptadecan-6-one 1.75-hydrate, C15H24N2O·1.75H2O (Matrine-H). Each derivative exhibited a consistent molecular conformation for the matrine core, which is notably distinct from that of the anhydrous form. Notably, both salts crystallized in the orthorhombic space group P212121, with an asymmetric unit featuring one cation and one anion. Within the two salt structures, intermolecular proton transfer between matrine and the acid is observed, culminating in the formation of a matrine cation protonated at the tertiary amine N site. The Matrine-CA crystal packing is manifested as a three-dimensional (3D) network arising from one-dimensional (1D) supramolecular helical chains, stabilized by N-H...O and O-H...O hydrogen bonds. In the case of Matrine-SA, the matrine cation is interconnected via hydrogen bonds with salicylate anions and water molecules, also forming a 1D helical motif. The structure of the hydrate form, Matrine-H, is reported again with the disordered solvent molecules accurately located. To further elucidate the structural attributes, Hirshfeld surface analysis and fingerprint plots are employed, offering a nuanced perspective on the intermolecular contacts and interactions within these crystalline forms.

Objective: To establish collection methods and laboratory testing methods for qualitative and quantitative analysis of 9 typical active pharmaceutical ingredient in the workplace air. Methods: In December 2021, a mixed solution of nine analytes was prepared and then dispersed in aerosol state to simulate sampling. Glass fiber filter membrane was selected as air collector and collected active pharmaceutical ingredient in the air at a rate of 2.0 L/min for 15 minutes. Then, the obtained filter membrane samples were eluted with 25%ACN/75%MeOH. Finally, the eluent was qualitatively and quantitatively analyzed with liquid chromatography-triple quadrupole mass spectrometer. Results: This method could effectively collect active pharmaceutical ingredient in the air, with an average sampling efficiency of more than 98.5%. The linear correlation coefficient r was greater than 0.9990. The lower limit of quantification for each analyte ranged from 0.6~500.0 ng/ml, and the average recovery rate ranged from 97.6%~102.5%. Conclusion: This method could simultaneously collect 9 active pharmaceutical ingredient in the workplace air, and could provide accurate qualitative and quantitative analysis in subsequent laboratory tests.
目的： 通过建立工作场所空气中活性药物成分的现场采集和实验室检测方法，实现对常见9种典型活性药物成分的定性、定量分析。 方法： 于2021年12月，配制9种分析物混合液，后制成气溶胶状态进行模拟采样。选择玻璃纤维滤膜作为采样介质，以2.00 L/min的速率对模拟现场样进行15min采气收集，并将得到的滤膜样品于25%乙腈/75%甲醇洗脱液中洗脱，以液相色谱-三重四级杆质谱联用仪对洗脱液进行定性、定量分析。 结果： 本方法可有效采集空气中的活性药物成分，平均采样效率≥98.5%，且各项检测参数良好，线性相关系数r均>0.999 0；各目标分析物最低定量浓度范围为4.00×10(-5)~3.33×10(-2) mg/m(3)；平均加标回收率范围为97.6%~102.5%。 结论： 本方法可同时对空气中9种活性药物成分进行采集，并能够在后续实验室检测中进行准确定性和定量,符合国家测定方法研制标准。.

Drug polymorphism is an important factor affecting the drugs quality and clinical efficacy. Therefore, great attention should be paid to the crystal analysis of drugs with their researching and evaluating part. With the booming development of Raman spectroscopy in recent years, more and more crystal analysis investigations were based on vibrational spectroscopy. This review mainly discussed the qualitative and quantitative analysis of active pharmaceutical ingredients (API) and pharmaceutical preparation with Raman spectroscopy. On basis of the determination of the vibration mode of drug molecules and the analysis of their chemical structure, this method had the advantages of universal, non-destructive, fast determination, low samples and cost, etc. This review provides theoretical and technical support for crystal structure, which are worth popularizing. It is expected that it will be helpful to relevant government management institutions, pharmaceutical scientific research institutions and pharmaceutical manufacturers.

OBJECTIVE: The aim of this study is to convert tretinoin (Tr), an active pharmaceutical ingredient (API), into ionic liquid for improving aqueous solubility and permeability of Tr in transdermal drug delivery applications.
METHODS: Three ionic liquids of Tr (TrILs) were synthesized through neutralization reactions, which were characterized to confirm the compositions and ionic interactions. The in vitro drug release studies and skin penetration tests were carried out to assess the performance of formulations containing TrILs.
RESULTS: The TrIL formed by choline and Tr at the molar ratio of 2:1 (2[Ch][Tr]), was found to have prominent solubility, stability as well as permeability. In contrast with the insoluble Tr, 2[Ch][Tr] presented as clear and transparent aqueous solution even after diluted to 14%. The aqueous solution of 2[Ch][Tr] demonstrated better permeation effect, of which the solution with 20% of 2[Ch][Tr] showed the optimal delivery efficiency in both epidermis (2.09 ± 0.18‰) and dermis (3.31 ± 0.48‰), realizing the improvement on the permeability of API. Meanwhile, TrILs can be easily fabricated as o/w emulsions as transdermal formulation. The emulsions are also able to improve the skin permeability of Tr, though the enhanced effect is inferior to TrILs solutions.
CONCLUSIONS: Ionic liquid technology can be used to improve solubility and permeability of Tr, providing a high potential strategy for the development of topical formulations and the desired transdermal application of drugs.

Few therapeutic specialty molecules from in vitro cultures beyond paclitaxel have come to market and although other more complex products like ginseng have also appeared, success has been limited. Often it is not the science that is limiting, but rather regulatory issues that limit considerations of potential products mainly because of costs in getting the product to market. Here we discuss broader thinking of such specialty molecules in the form of dietary supplements, nutraceuticals, herbal medicines, botanical drugs, and pure molecules along with potential complex products from a regulatory standpoint and especially within the realm of approved botanical drugs, e.g., Veregen and Fulyzaq, that have new drug applications (NDAs). The United States food and drug administration (US FDA) regulatory categories are used to provide examples of alternative product options that could prove useful for taking specialty molecules to market.

The objective of this review is to describe the evolution of lung tissue-derived diploid progenitor cell applications, ranging from historical biotechnological substrate functions for vaccine production and testing to current investigations around potential therapeutic use in respiratory tract regenerative medicine. Such cell types (e.g., MRC-5 or WI-38 sources) were extensively studied since the 1960s and have been continuously used over five decades as safe and sustainable industrial vaccine substrates. Recent research and development efforts around diploid progenitor lung cells (e.g., FE002-Lu or Walvax-2 sources) consist in qualification for potential use as optimal and renewed vaccine production substrates and, alternatively, for potential therapeutic applications in respiratory tract regenerative medicine. Potentially effective, safe, and sustainable cell therapy approaches for the management of inflammatory lung diseases or affections and related symptoms (e.g., COVID-19 patients and burn patient severe inhalation syndrome) using local homologous allogeneic cell-based or cell-derived product administrations are considered. Overall, lung tissue-derived progenitor cells isolated and produced under good manufacturing practices (GMP) may be used with high versatility. They can either act as key industrial platforms optimally conforming to specific pharmacopoeial requirements or as active pharmaceutical ingredients (API) for potentially effective promotion of lung tissue repair or regeneration.

Ionic liquids (ILs) have been widely used in biomedical and pharmaceutical fields as solvents or permeation enhancers. Recently, more and more researchers focused on optimizing the physicochemical properties of active pharmaceutical ingredient (API) by ILs technology. Converting APIs into ILs (API-ILs) has shown great potential for drug delivery by eliminating polymorphism, tailoring solubility, improving thermal stability, increasing dissolution, controlling drug release, modulating the surfactant properties, enhancing permeability of APIs and modulating cytotoxicity on tumor cells. In addition, API-ILs are also used in various formulations as active ingredients, such as solutions, emulsions, even tablets or nanoparticles. This paper aims to review current status of API-ILs, including the rational and design, preparation and characterization, the improvement on the physicochemical characteristics of APIs, the compatibility of API-ILs with various formulations, and the future prospects of API-ILs in biomedical and pharmaceutical fields.

The development of an effective pharmacological countermeasure is needed to reduce the morbidity and mortality in high-dose ionizing radiation-induced acute damage. Genistein has shown bioactivity in alleviating radiation damage and is currently synthesized by chemosynthetic methods. Due to concerns about chemical residues and high costs, the clinical application of genistein is still a major challenge. In this study, we aimed to establish an efficient method for the extraction of genistein from Fructus sophorae. The effects of extracted genistein (FSGen) on preventing intestinal injury from radiation were further investigated in this study. C57/BL mice were exposed to 7.5 Gy whole body irradiation with and without FSGen treatments. Histological analysis demonstrated significant structural and functional restitution of the intestine and bone marrow in FSGen-pretreated cohorts after irradiation. Through mRNA expression, protein expression, and small interfering RNA analyses, we demonstrated that FSGen protects IEC-6 cells against radiation damage by upregulating the Rassf1a and Ercc1 genes to effectively attenuate DNA irradiation damage. Together, our data established an effective method to extract genistein from the Fructus sophorae plant with high purity, and validated the beneficial roles of the FSGen in protecting the radiation damage. These results promise the future applications of Fructus sophorae extracted genistein in the protection of radiation related damages.

BACKGROUND: Development of controlled drug delivery systems can improve the pharmacokinetic characteristics of drug molecules in the human body, thereby significantly improving the utilization rate of drugs and reducing toxicity and side effects caused by their high concentrations, which can occur when delivery is not controlled. Metal organic frameworks are a new class of very promising crystalline microporous materials, especially when the size is reduced to the nanometer range. Metal-organic frameworks exhibit large specific surface areas, tunable compositions, and easy functionalization. In recent years, an increasing number of studies have reported the remarkable advances in multifunctional nanoscale metal-organic frameworks in drug delivery.
OBJECTIVE: To review the latest research involving advances in stimuli-responsive nanoscale metal organic frameworks as drug delivery systems in controlled-release drugs.
CONCLUSIONS: We first introduce the two main strategies associated with nanoscale metal organic frameworks used in drug loading: direct assembly and post-encapsulation. We next focus on the latest discoveries of nanoscale metal-organic framework-based stimulus response systems for drug delivery, including pH, magnetics, light, ion, temperature, and other stimuli, as well as multiple stimulus- responsive drug delivery systems. Finally, we discuss the challenges and future developmental directions of nanoscale metal-organic framework-based controlled drug release.

As an inflammatory skin disease of pilosebaceous follicles, Propionibacterium acnes (P. acnes) can aggravate local inflammatory responses and forms acne lesions. However, due to the skin barrier, various transdermal measures other than antibiotic creams are necessary. Microneedle (MN) patches are emerging platforms for the transdermal delivery of various therapeutics since it can effectively create transport pathways in the epidermis. Herein, we develop an active pharmaceutical ingredient poly(ionic liquid) (API PIL)-based MN patches containing salicylic acid (SA). The PIL-based MNs are simply prepared through photo-crosslinking of an imidazolium-type ionic liquid (IL) monomer in MN micro-molds, and following by anion exchange with salicylic acid anions (SA-). The fabricated SA-loaded PIL-MNs exhibited therapeutic efficiency in the topical treatment of P. acnes infection in vitro and in vivo. These active pharmaceutical ingredient PIL-based MNs can improve acne treatment, demonstrating potential applications for skin diseases. STATEMENT OF SIGNIFICANCE: Microneedle (MN) patches can be used as platforms for transdermal delivery of various therapeutics to treat bacterial infection. Here, a facile strategy was developed to synthesize active pharmaceutical ingredient poly(ionic liquid)-based microneedle patches by anion-exchange with salicylic acid anion (SA-). The fabricated SA-loaded PIL-MNs are active on not only anti-bacteria but also anti-inflammation in P. acnes treated mice, and may have potential applications for skin acne infection.