Parenteral protein formulations: An overview of approved products within the European Union.

The study presented is a comprehensive overview of commercial parenteral protein formulations, approved by the European Medicines Agency (EMA), 1995-2018. The objective of this overview was to analyse current trends in the design of commercial parenteral protein products and thereby support formulation scientists in the design of new formulations. The main data source was the publicly available European Public Assessment Reports (EPARs) published by the EMA for each authorised product. An analysis of the percentage of formulations in a liquid and lyophilised form was conducted. In addition, the number of products containing individual excipients, classified into functional categories is provided. Finally, the overview includes comprehensive details of product compositions obtained from EMA, US Food and Drug Administration (FDA) and product Marketing Authorisation Holder. Data analysis highlighted trends in the number of products approved, and the higher percentage of liquid parenteral protein formulations (66%) compared to lyophilised formulations (34%). This overview identifies the most commonly incorporated excipients employed as buffering agents, stabilisers/bulking agents, surfactants, preservatives and tonicifiers, including their concentration ranges of use in both liquid and lyophilised formulation approaches. Finally, antibody-based formulations were a particular focus of this overview. The relationship between parenteral routes of administration and antibody concentrations in approved products was also investigated.

In vitro effect of Acanthospermum australe (Asteraceae) extracts on Acanthamoeba polyphaga trophozoites / Efeito in vitro de extratos de Acanthospermum australe (Asteraceae) sobre trofozoitos de Acanthamoeba polyphaga

Acanthamoeba is a free-living protozoan widely distributed in the environment, occurring in vegetative trophozoite and resistance cyst stages during its life cycle. It constitutes an etiological agent of Acanthamoeba keratitis, a disease that may cause severe ocular inflammation and blindness. New drugs can be developed from molecules found in plants and thus help in its difficult treatment. Acanthospermum australe (Asteraceae), a plant used in folk medicine, had its effect tested on Acanthamoeba polyphaga. Aqueous and ethanolic extracts of A. austral were obtained from aerial parts for infusion and static maceration, respectively. Concentrations of 10, 5, 2.5, 1.25 and 0.625 mg/ml of the extract were tested against Acanthamoeba polyphaga trophozoites. The cytotoxic effect of the extracts was tested in mammalian cells using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: The 10 mg/ml concentration of ethanolic extract was lethal to 100% of the A. polyphaga trophozoites in 24 h and both extracts presented cytotoxic effect against mammalian cells. These findings suggest that the A. austral ethanolic extract may have compounds with relevance to the development of new amoebicidal drugs.

Acanthamoeba é um protozoário de vida livre amplamente distribuído no ambiente, ocorrendo sob a forma trofozoítica (metabolicamente ativa) e cística (de resistência), durante seu ciclo de vida. O protozoário constitui um agente etiológico da Ceratite Amebiana, uma doença que pode causar inflamação ocular severa e cegueira. Novos fármacos podem ser desenvolvidos a partir de moléculas encontradas em plantas e assim ajudar em seu difícil tratamento. Aqui, Acanthospermum australe (Asteraceae), uma planta utilizada na medicina popular, teve seu efeito sobre trofozoítos de Acanthamoeba polyphaga testado. O extrato aquoso e etanólico de A. australe foram obtidos das partes aéreas por infusão e maceração estática, respectivamente. As concentrações 10, 5, 2,5, 1,25 e 0,625 mg/ml dos extratos foram testadas contra trofozoítos do protozoário. O efeito citotóxico dos extratos foi testado em células de mamífero utilizando o ensaio de brometo de 3-[4,5-dimetiltiazol-2-il]-2,5-difeniltetrazólio (MTT). A concentração de 10 mg/ml do extrato etanólico foi letal a 100% dos trofozoítos de A. polyphaga em 24 h e ambos os extratos apresentaram efeito citotóxico contra as células de mamífero. Estes resultados sugerem que o extrato etanólico de A. australe pode ter componentes com relevância para o desenvolvimento de novos fármacos amebicidas.

Assessment of the antimicrobial effect of three plants used for therapy of community-acquired urinary tract infection in Rio Grande do Sul (Brazil).

ETHNOPHARMACOLOGICAL RELEVANCE: The urinary tract infections (UTI) are among the infectious diseases of bacterial origin most commonly diagnosed, and may result in a significant mortality. The microorganisms most frequently involved in community-acquired infections are Escherichia coli and Klebsiella pneumoniae, both Gram-negative bacillus of the Enterobacteriaceae family. In southern Brazil, it is common the treatment of UTI using herbs and teas, a tradition inherited from the ancient indigenous people. Nevertheless, there is still poor scientific information about the action of these plants. MATERIALS AND METHODS: Tests included the determination of minimum inhibitory concentration (MIC) by microdilution method at concentrations of 5000-156.25 µg/µL, and evaluation of antimicrobial activity by agar disc diffusion method at concentrations 500-12.5 µg/µL, against the microorganisms Escherichia coli and Klebsiella pneumoniae. RESULTS: In the tests for MIC and antimicrobial activity by disc diffusion method in agar, the growth of Escherichia coli and Klebsiella pneumoniae isolates were not inhibited by extracts from Piptochaetium montevidense, Bulbostylis capillaris and Juncus capillaceus employed in the study. CONCLUSIONS: Despite the popular use of the plants used in this study, there is no relation between the use and the expected antimicrobial activity. Prolonged use of these plants may worsen the disease and lead to kidney involvement, and in severe cases, lead to death.

Antifungal activity of some Brazilian Hypericum species.

Crude methanolic extracts and fractions from the aerial parts of seven species of Hypericum (H. caprifoliatum Cham. and Schltdl., H. carinatum Griseb., H. connatum Lam., H. ternum A. St.-Hil., H. myrianthum Cham. and Schltdl., H. piriai Arechav. and H. polyanthemum Klotzsch ex Reichardt) growing in southern Brazil were analyzed for their in vitro antifungal activity against a panel of standardized and clinical opportunistic pathogenic yeasts and filamentous fungi, including dermatophytes, by the agar dilution method. Chloroform and hexane extracts of H. ternum showed the greatest activity among extracts tested.

Antimicrobial activity of some Hypericum species.

The crude methanolic extracts of six species of Hypericum [H. caprifoliatum Cham. & Schlecht., H. carinatum Griseb., H. connatum Lam., H. ternum A. St. Hil., H. myrianthum Cham. & Schlecht. and H. polyanthemum Klotzsch ex Reichardt] growing in southern Brazil were analyzed for antimicrobial activity against several microorganisms (bacteria and fungi). The most active plant was H. caprifoliatum, which showed activity against Staphylococcus aureus. Only H. polyanthemum and H. ternum extracts were active against Bacillus subtilis. None of the crude methanolic extracts showed activity against S. epidermidis, Escherichia coli or Saccharomyces cerevisiae. Extracts from these species were evaluated chemically and tannin, flavonoid and phenolic acids were the prominent compounds. The plants contained quercitrin, hyperoside (except H. connatum) and, less frequently, isoquercitrin and chlorogenic acid. In contrast to H. perforatum, which has high concentrations of rutin, these species do not produce this flavonoid or it appears as traces. The tannin concentration varied between 5.1 and 16.7% in H. myrianthum and H. ternum, respectively.

The use of complex polysaccharides in the management of metabolic diseases: the case of Solanum lycocarpum fruits.

In the Brazilian cerrado, a preparation obtained from the fruits of Solanum lycocarpum St.-Hil. (Solanaceae), popularly known as 'fruta-de-lobo' (wolf-fruit), have been widely employed for diabetes management, obesity and to decrease cholesterol levels. The medicinal preparation consists of the green fruits which are ground in aqueous solution and filtered. The white 'gum' deposited is decanted and slowly dried providing a powder which is commercialized in capsules with the name of 'polvilho-de-lobeira'. Through phytochemical analysis of this phytomedicine and the fruit of S. lycocarpum we found polysaccharides as the main component. Some polysaccharides slow gastric emptying and act on the endocrinous system affecting the liberation of gastrointestinal hormones, lowering blood glucose levels. The hypocholesterolemic activity could be due to the increased fecal bile acid excretion as well as to the action of the short-chain fatty acids, coming from fermentation, on the synthesis of delta-aminolevulinate and by the increase of the cholesterol 7-alpha-hydroxylase and 3-hydroxy-3-methylglutaryl CoA reductase synthesis.