Development and evaluation of the in vitro schistosomicidal activity of solid dispersions based on 2-(-5-bromo-1-H-indole-3-yl-methylene)-N-(naphthalene-1-ylhydrazine-carbothiamide.

Among all the neglected diseases, schistosomiasis is considered the second most important parasitic infection after malaria. Praziquantel is the most widely used drug for this disease, but its exclusive use may result in the development of drug-resistant schistosomiasis. To increase the control of the disease, new drugs have been developed as alternative treatments, among them 2-(-5-bromo-1-h-indole-3-yl-methylene)-N-(naphthalene-1-ylhydrazine-carbothiamide (LQIT/LT-50), which showed promising schistosomicidal activity in nonclinical studies. However, LQIT/LT-50 presents low solubility in water, resulting in reduced bioavailability. To overcome this solubility problem, the present study aimed to develop LQIT/LT-50 solid dispersions for the treatment of schistosomiasis. Solid dispersions were prepared through the solvent method using Soluplus©, polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP K-30) as hydrophilic carriers. The formulations with the best results in the compatibility tests, aqueous solubility and preliminary stability studies have undergone solubility tests and physicochemical characterizations by Fourier-transform infrared spectroscopy (FTIR), x-ray diffractometry (XRD), exploratory differential calorimetry (DSC), thermogravimetry (TG) and Raman spectroscopy. Finally, the schistosomicidal activity was evaluated in vitro. The phycochemical analyzes showed that when using PVP K-30, there was an interaction between the PVP K-30 and LQIT/LT-50, proving the successful development of the solid dispersion. Furthermore, an increase in the solubility of the new system was observed (LQIT/LT-50:PVP K-30) in addition to the improvement in the in vitro shistosomidal activity at 1:4 (w/w) molar ratio (i.e., 20% drug loading) when compared to LQIT/LT-50 alone. The development of the LQIT/LT-50:PVP K-30 1:4 solid dispersion is encouraging for the future development of new pharmaceutical solid formulations, aiming the schistosomicidal treatment.

Herbal Technological Prospects of Morus nigra L.: A Systematic Patent Analysis Review.

BACKGROUND: Morus nigra L. is a plant with significant potential for drug development due to the presence of numerous bioactive compounds in its various parts. OBJECTIVES: This article aims to compile the technological perspectives of Morus nigra L. towards drug development and therapeutic indications based on registered patents in databases. METHODS: The study analyzed patents published within the last five years, focusing on products derived from different parts of the Morus nigra L. plant. Patent databases such as the European Patent Office (EPO), the United States Patent and Trademark Office (USPTO), the World Intellectual Property Organization (WIPO), and the National Institute of Industrial Property Databases (INPI) were examined. RESULTS: A total of 45 patents were categorized by country of origin, type of applicant, extraction method, and therapeutic indications. China had the highest number of patent filings (43.48%), and private companies were the primary technology patent holders (38.64%). Noteworthy extraction methods included ultrasound-assisted extraction, decoction, infusion, and maceration. The most utilized plant parts were leaves (44.44%), followed by fruits (35.56%), root bark (15.56%), and stems (4.44%). The main therapeutic indications identified were the treatment of hyperglycemia and dyslipidemia (43.33%), along with digestive problems, cosmetics, nutrition, and cleaning applications. CONCLUSION: The study of patents covers discoveries and advancements often absent in scientific articles, making a review focused on this advanced information crucial for expanding existing scientific knowledge. Even if some therapies have been explored previously, patents can reveal innovative approaches and fresh perspectives that contribute to sustained scientific progress.

pH-responsive phthalate cashew gum nanoparticles for improving drugs delivery and anti-Trypanosoma cruzi efficacy.

Nanotechnology is a crucial technology in recent years has resulted in new and creative applications of nanomedicine. Polymeric nanoparticles have increasing demands in pharmaceutical applications and require high reproducibility, homogeneity, and control over their properties. Work explores the use of cashew phthalate gum (PCG) as a particle-forming polymer. PCG exhibited a pH-sensitive behavior due to the of acid groups on its chains, and control drug release. We report the development of nanoparticles carrying benznidazole. Formulations were characterized by DLS, encapsulation efficiency, drug loading, FTIR, pH-responsive behavior, release, and in vitro kinetics. Interaction between polymer and drug was an evaluated by molecular dynamics. Morphology was observed by SEM, and in vitro cytotoxicity by MTT assay. Trypanocidal effect for epimastigote and trypomastigote forms was also evaluated. NPs responded to the slightly basic pH, triggering the release of BNZ. In acidic medium, they presented small size, spherical shape, and good stability. It was indicated NP with enhanced biological activity, reduced cytotoxicity, high anti T. cruzi performance, and pH-sensitive release. This work investigated properties related to the development and enhancement of nanoparticles. PCG has specific physicochemical properties that make it a promising alternative to drug delivery, however, there are still challenges to be overcome.

Drug associations as alternative and complementary therapy for neglected tropical diseases.

The present paper aims to establish different treatments for neglected tropical disease by a survey on drug conjugations and possible fixed-dose combinations (FDC) used to obtain alternative, safer and more effective treatments. The source databases used were Science Direct and PubMed/Medline, in the intervals between 2015 and 2021 with the drugs key-words or diseases, like "schistosomiasis", "praziquantel", "malaria", "artesunate", "Chagas' disease", "benznidazole", "filariasis", diethylcarbamazine", "ivermectin", " albendazole". 118 works were the object of intense analysis, other articles and documents were used to increase the quality of the studies, such as consensuses for harmonizing therapeutics and historical articles. As a result, an effective NTD control can be achieved when different public health approaches are combined with interventions guided by the epidemiology of each location and the availability of appropriate measures to detect, prevent and control disease. It was also possible to verify that the FDCs promote a simplification of the therapeutic regimen, which promotes better patient compliance and enables a reduction in the development of parasitic resistance, requiring further studies aimed at resistant strains, since the combined APIs usually act by different mechanisms or at different target sites. In addition to eliminating the process of developing a new drug based on the identification and validation of active compounds, which is a complex, long process and requires a strong long-term investment, other advantages that FDCs have are related to productive gain and gain from the industrial plant, which can favor and encourage the R&D of new FDCs not only for NTDs but also for other diseases that require the use of more than one drug.

A Review of Analytical Methods for Calcium Salts and Cholecalciferol in Dietary Supplements.

Dietary supplements composed by the combination of a calcium salt with cholecalciferol (vitamin D3) are widely used for improving bone health in conditions caused by the deficiency of these compounds in the body. Historically, these supplements have been linked to quality and safety issues. In the case of calcium salts, the presence of potentially toxic contaminants such as lead (Pb) has already been alerted by health authorities from different countries. Meanwhile, cholecalciferol is very unstable under inadequate manufacturing and storage conditions. The content of both compounds in commercial dietary supplements is often found to be in disagreement with the label claims, which can lead to a deficient or excessive nutrient intake by consumers. In this scenario, analyzing these compounds is still a difficult and time-consuming task, which usually requires specific pretreatment procedures and multiple analytical methods due to the inorganic nature of calcium and the organic nature of cholecalciferol. Therefore, this article reviews the analytical methods, described in official compendia and scientific literature, for the determination of calcium salts and cholecalciferol in dietary supplement formulations. We also approached the sample preparation procedures highly required due to the matrix complexity of these materials.

Cutaneous leishmaniasis: new oral therapeutic approaches under development.

The World Health Organization (WHO) classifies leishmaniasis as a disease for which the development of new treatments is a priority. Available drugs are not fully effective in all cases; they have parenteral administration and exhibit serious and common adverse effects. The only oral drug available (miltefosine) has shown resistance, is expensive, and is not available in many endemic countries. Thus, the development of an oral medicine may solve many of these issues. Based on that, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs for the treatment of cutaneous leishmaniasis. A literature search for keywords "leishmania and oral" was performed in PubMed and ScienceDirect, considering articles published in the last 5 years. The articles were selected based on the objective of the review. The main problem in the current treatment of leishmaniasis is the administration of injectables, since it requires patients to travel to health centers, hospitalization, and professional administration, conditions that are not adapted to the socioeconomic reality of patients. Therefore, many research studies have evaluated oral alternatives for the treatment of cutaneous leishmaniasis. The main tested approaches were obtaining new molecules, repositioning drugs, and new formulations of old drugs. The prospects are encouraging but still require more in vivo bioavailability and clinical trials.

Benznidazole in vitro dissolution release from a pH-sensitive drug delivery system using Zif-8 as a carrier.

Chagas disease is a neglected tropical disease caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi). Endemic in underdeveloped and developed countries, due to the migratory movement, it is considered a serious public health problem. Endemic in underdeveloped countries and due to the migratory movement, in developed countries as well, it is considered a serious public health problem. One of the reasons for this is a weak therapeutic arsenal, represented only by the drug benznidazole (BNZ) which, although it promotes significant cure rates in the acute phase of the disease, presents serious problems of toxicity and bioavailability, mainly due to its low aqueous solubility. Several studies have presented several drug delivery systems (DDS) based on BNZ aiming at enhancing its solubility in aqueous medium and, with this, promoting an increase in the dissolution rate and, consequently, in its bioavailability. However, the present work is a pioneer in using a zeolitic imidazolate framework as a carrier agent for a DDS in order to promote a pH-sensitive modulation of the drug. Thus, this work aimed to develop a novel DDS based on BNZ and the ZIF-8 to use it in development of prolonged-release dosage forms to alternative treatment of Chagas disease. The BNZ@ZIF-8 system was obtained through an ex situ method selected due to its higher incorporation efficiency (38%). Different characterization techniques corroborated the obtainment and drug release data were analyzed by in vitro dissolution assay under sink and non-sink conditions and setting the kinetic results through both model dependent and independent methods. Under sink conditions, at pH 4.5, BNZ and BNZ@ZIF-8 showed similar release profile, but the DDS was effective in promoting a prolonged release. At pH 7.6, after 7 h, BNZ showed a lower release than BNZ@ZIF-8. On the other hand, in non-sink conditions at pH 4.5 the BNZ presented 80% of drug release in 3 h, while the DDS in 6 h. At pH 7.6, BNZ presented a release of 80% in 2 h, while the DDS reaches it in only at 12 h. Therefore, at pH 4.5 the DDS BNZ@ZIF-8 showed a faster release with a burst effect, while at pH 7.6 it showed a prolonged and controlled release. Finally, it is evident that a promising DDS pH-sensitive was obtained as a novel carrier that might be able to prolongs BNZ release in dosage forms intended for the alternative treatment of Chagas disease.

Metal organic frameworks (MOFs) with therapeutic and biomedical applications: a patent review.

Introduction: Metal organic frameworks (MOFs) are a recent group of nano porous materials with exceptional physical properties, such as large surface areas, high pore volumes, low densities and well-defined pores. This type of material has been used frequently for biomedical and therapeutic applications, such as drug delivery systems and theranostic materials.Areas covered: In this review, the authors searched for patents filed in the last 10 years, found in different databases, related to the therapeutic or biomedical application of MOFs for use in different health fields. The possibility of these new materials becoming new therapeutic possibilities available to the population was emphasized.Expert opinion: The advances in research with MOFs have grown in the last 10 years and with that many possibilities for their applications have emerged in several areas, especially biomedical. The possibility of using these materials in drug delivery systems is the most common form of possibility of use in the health area, mainly due to easy obtaining and high reproducibility, which are seen very positively by the drug development technology sector.

Obtainment of the spray-dried extracts of Peperomia pellucida L. (H.B.K.) using different atomization temperatures: physicochemical characterization and technological development for pharmaceutical applications.

Spray-dried extracts are prepared as powders or granules after solvent removal, which can be obtained in the presence or absence of pharmaceutical adjuvants. This work aimed to optimize the process of obtaining dried extracts of Peperomia pellucida L. (HBK) by spray drying. The characterization of the extract was performed by thermal analysis, specific surface area, particle size and high performance liquid chromatography (HPLC); then, capsules were developed for antimicrobial treatment, evaluating four bench lots by the determination of the angle of repose and time of flow, scanning electron microscopy, porosity and physicochemical quality control. There were no significant differences between the extracts obtained by spray drying at atomization temperatures of 140 °C, 160 °C and 180 °C, which was confirmed by thermal analysis. Specific surface area varied inversely with the mean particle size. Regarding the marker content by HPLC, no significant differences were found between the samples, although the flavonoid fraction was more stable at 160 °C. Bench lots (I to IV) were developed using the diluents Flowlac®, Starch® 1500, microcrystalline cellulose 250 and Cellactose® 80. Based on the results, the bench lot I, containing Flowlac®, was selected. The results of physicochemical quality control demonstrated that the selected formulation meets the pre-established parameters, and proving to be economically viable.

Beta-lapachone: Natural occurrence, physicochemical properties, biological activities, toxicity and synthesis.

ß-Lapachone is an ortho-naphthoquinone originally isolated from the heartwood of Handroanthus impetiginosus and can be obtained through synthesis from lapachol, naphthoquinones, and other aromatic compounds. ß-Lapachone is well known to inhibit topoisomerase I and to induce NAD(P)H: quinone oxidoreductase 1. Currently, phase II clinical trials are being conducted for the treatment of pancreatic cancer. In view of ever-increasing scientific interest in this naphthoquinone, herein, the authors present a review of the synthesis, physicochemical properties, biological activities, and toxicity of ß-lapachone. This natural compound has shown activity against several types of malignant tumors, such as lung and pancreatic cancers and melanoma. Furthermore, this ortho-naphthoquinone has antifungal and antibacterial activities, underscoring its action against resistant microorganisms and providing anti-inflammatory, antiobesity, antioxidant, neuroprotective, nephroprotective, and wound-healing properties. ß-Lapachone presents low toxicity, with no signs of toxicity against alveolar macrophages, dermal fibroblast cells, hepatocytes, or kidney cells.

Microwave-initiated rapid synthesis of phthalated cashew gum for drug delivery systems.

Chemical modification of polysaccharides is an important approach for their transformation into customized matrices that suit different applications. Microwave irradiation (MW) has been used to catalyze chemical reactions. This study developed a method of MW-initiated synthesis for the production of phthalated cashew gum (Phat-CG). The structural characteristics and physicochemical properties of the modified biopolymers were investigated by FTIR, GPC, 1H NMR, relaxometry, elemental analysis, thermal analysis, XRD, degree of substitution, and solubility. Phat-CG was used as a matrix for drug delivery systems using benznidazole (BNZ) as a model drug. BNZ is used in the pharmacotherapy of Chagas disease. The nanoparticles were characterized by size, PDI, zeta potential, AFM, and in vitro release. The nanoparticles had a size of 288.8 nm, PDI of 0.27, and zeta potential of -31.8 mV. The results showed that Phat-CG has interesting and promising properties as a new alternative for improving the treatment of Chagas disease.

ZIF-8 as a promising drug delivery system for benznidazole: development, characterization, in vitro dialysis release and cytotoxicity.

Chagas disease (CD), caused by the flagellate protozoan Trypanosoma cruzi, is one of the major public health problems in developing countries. Benznidazole (BNZ) is the only drug available for CD treatment in most countries, however, it presents high toxicity and low bioavailability. To address these problems this study used Zeolitic Imidazolate Framework-8 (ZIF-8), which has garnered considerable attention due to its potential applications, enabling the controlled delivery of drugs. The present work developed and characterized a BNZ@ZIF-8 system, and the modulation of BNZ release from the ZIF-8 framework was evaluated through the in vitro dialysis release method under sink conditions at different pH values. Moreover, the in vitro evaluation of cell viability and cytotoxicity by MTT assay were also performed. The dissolution studies corroborated that a pH sensitive Drug Delivery System capable of vectorizing the release of BNZ was developed, may leading to the improvement in the bioavailability of BNZ. The MTT assay showed that no statistically significant toxic effects occurred in the developed system, nor significant effects on cell viability.

Prolonged Release of Anti-Retroviral Efavirenz From System Using ZIF-8 as Carrier.

BACKGROUND: Acquired Immunodeficiency Syndrome (AIDS) is a major public health problem in the world. One of the highly effective drugs in anti-HIV therapy is efavirenz (EFZ), which is classified as Class II according to the Classification System of Biopharmaceuticals, presenting low solubility and high permeability, this being an obstacle related to the drug. OBJECTIVE: This study aimed to obtain an innovative system based on EFZ and the Zeolitic Imidazolate Framework (ZIF-8) to use in the development of prolonged-release pharmaceutical forms that can circumvent this problem. METHODS: The EFZ: ZIF-8 system was obtained by a selected ex-situ method due to its higher incorporation efficiency. Different characterization techniques corroborated the obtainment of the system, and drug release was analyzed by dissolution testing under sink conditions, the profiles being adjusted to some kinetic models. RESULTS: At pH 1.2, the structure of ZIF-8 breaks down rapidly, releasing a large amount of drug within either 3h or short time. In the pH 4.5 and 6.8 medium, the EFZ release from the EFZ: ZIF-8 system obtained in ethanol was prolonged, releasing 95% of the drug in 24h at pH 4.5 and 75% medium at pH 6.8. CONCLUSION: It is evident that a promising pH-sensitive system was obtained using ZIF-8 as a novel carrier of EFZ intended for the alternative treatment of AIDS.

Recent strategies for the development of oral medicines for the treatment of visceral leishmaniasis.

Considered prevalent in many countries on five continents, especially in low-income regions, leishmaniasis is a neglected tropical disease classified by World Health Organization as one of the diseases for which the development of new treatments is a priority. It is an infectious disease caused by protozoa of the genus Leishmania, whose species may cause different clinical manifestations, such as cutaneous and visceral leishmaniasis (VL). Treatment is exclusively by drug therapy, as it has not been possible to develop vaccines yet. Currently available drugs are not fully effective in all cases; they have parenteral administration and exhibit a number of serious and very common adverse effects. The only oral drug available is expensive and it is not available in many endemic countries. Injectable administration is the main problem of treatments, since it requires patients to go to health centers, hospitalization and professional administration, which are conditions that are not adapted to the reality of the poverty conditions of patients with the disease. In this context, the development of an oral medicine has become a focus as it may solve many of these issues. Based on this scenario, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs directed to the treatment of human VL.

Lipid Nanoparticles as a Skin Wound Healing Drug Delivery System: Discoveries and Advances.

Chronic wounds are a remarkable cause of morbidity, requiring long-time treatments with a significant impact on the quality of life and high costs for public health. Although there are a variety of topical skin preparations commercially available, they have several limitations that frequently impair wound healing, such as drug instability, toxicity, limited time of action and ineffective skin permeation. In recent years, researchers have focused on the development of new effective treatments for wound healing and shown frequent interest in nanometric drug delivery systems to overcome such obstacles. In dermatology, lipid nanoparticles (LNPs) have received great attention from researchers due to their great functionalities, greater adhesion to the skin and film formation, enabling the hydration and maintenance of skin integrity, as well as present a more effective penetration through the skin barrier. This review provides an update on topical formulations based on Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) as wound healing treatments. Both SLNs and NLCs are able to increase solubility and stability of active pharmaceutical ingredients and increase skin penetration compared to the free drugs. Additionally, SLNs and NLCs can increase pharmacological activity, increase the release profile of the drugs, promote synergistic effects and improve the sensory properties of the final formulation. Topical dosage forms containing nanoparticles have been extensively evaluated for wound healing activity, mainly the dressings, films and scaffolds. Therefore, lipid nanoparticles have contributed in improving wound healing therapies when incorporated into other dosage forms with better efficacy and lesser adverse effects than conventional formulations.

Development and Evaluation of Antimicrobial and Modulatory Activity of Inclusion Complex of Euterpe oleracea Mart Oil and ß-Cyclodextrin or HP-ß-Cyclodextrin.

The development of inclusion complexes is used to encapsulate nonpolar compounds and improve their physicochemical characteristics. This study aims to develop complexes made up of Euterpe oleracea Mart oil (EOO) and ß-cyclodextrin (ß-CD) or hydroxypropyl-ß-cyclodextrin (HP-ß-CD) by either kneading (KND) or slurry (SL). Complexes were analyzed by molecular modeling, Fourier-transform infrared spectroscopy, scanning electron microscopy, powder X-ray diffraction, thermogravimetry analysis and differential scanning calorimetry. The antibacterial activity was expressed as Minimum Inhibitory Concentration (MIC), and the antibiotic resistance modulatory activity as subinhibitory concentration (MIC/8) against Escherichia coli, Streptomyces aureus, Pseudomonas aeruginosa and Enterococcus faecalis. Inclusion complexes with ß-CD and HP-ß-CD were confirmed, and efficiency was proven by an interaction energy between oleic acid and ß-CD of -41.28 ± 0.57 kJ/mol. MIC values revealed higher antibacterial activity of complexes compared to the isolated oil. The modulatory response of EOO and EOO-ß-CD prepared by KND as well as of EOO-ß-CD and EOO-HP-ß-CD prepared by SL showed a synergistic effect with ampicillin against E. coli, whereas it was not significant with the other drugs tested, maintaining the biological response of antibiotics. The antimicrobial response exhibited by the complexes is of great significance because it subsidizes studies for the development of new pharmaceutical forms.

Product indiscriminate use of vitamin risks: A review.

Most of the population does not seek professional advice before taking vitamin products and their indiscriminate use can lead to serious health risks. This study aims to demonstrate, through bibliographic survey, the risks of indiscriminate use of vitamin products related to hypervitaminosis and major drug interactions which the multivitamins are involved. A bibliographic survey was conducted in the databases LILACS, SciELO, PubMed, Medline, Micromedex, Drugs.com and textbooks on the subject. Vitamins are commonly described as harmless products by the majority of the population, but these trace elements can interact with other substances, causing mild disconforts or treatment failure for the patient, severe consequences to the body and can lead to death. To avoid the indiscriminate use of vitamin products, it is necessary that health professionals know and use specific laboratory tests for the determination of vitamins in the body, preventing these products from being unnecesarily prescribed. Also, the knowledge about what the possible effects of the indiscriminate use of vitamin supplements can lead to the rational use of these products.

Análise de prescrições irregulares em uma rede de farmácias do Recife / Analysis of irregular prescriptions in a pharmacy of Recife

A prescrição é um "documento" essencial que visa à adesão farmacoterapêutica por meio da tradução completa de informações fundamentais sobre a terapia a ser seguida pelo paciente. Ela deve ser escrita de forma legível, à tinta e ao vernáculo, e conter todas as informações sobre o medicamento. Além disso, características referentes ao prescritor e ao paciente são indispensáveis, pois garantem a confiabilidade e a rastreabilidade da receita perante a Vigilância Sanitária e asseguram o uso racional de medicamentos. Atualmente, o número de prescrições ilegíveis é alto e esse fator contribui para o aparecimento de efeitos adversos, tóxicos e até letais, dependendo do caso. O presente estudo teve como objetivos avaliar as prescrições que apresentaram ilegibilidade, bem como sua origem, sua classificação e os principais erros de preenchimento. O projeto foi submetido e aprovado pelo Comitê de Ética. Realizou-se a pesquisa em um dos estabelecimentos da Rede de Farmácias Pague Menos®, durante o mês de junho de 2015, sendo analisadas 200 receitas consideradas ilegíveis. Das receitas analisadas, 43 (22%) não possibilitaram a dispensação do medicamento. Constatou-se, também, que a maioria das receitas veio de estabelecimentos públicos (60%) e que 74% era de controle especial. Além disso, observou-se a ausência de informações importantes no receituário, como duração do tratamento, posologia e data. Desse modo, essas características comprovam que a ilegibilidade é uma prática recorrente, que impossibilita uma dispensação segura de medicamentos nos estabelecimentos de saúde e, consequentemente, comprova a grande importância da padronização no preenchimento de receitas para que haja uma eficácia no tratamento.

The prescription is an essential "document" that aims to pharmacotherapeutic adherence through the complete translation of key information about the therapy to be followed by the patient. As such, it must be written legibly in ink and vernacular, and contain all the medicine information. In addition, features of the prescriber and the patient are indispensable, as they ensure the reliability and traceability of the recipe before the Health Surveillance, and ensure the rational use of medicines. Currently, the number of illegible prescriptions is high and this factor contributes to the appearance of side effects, toxic and even lethal damage, depending on the case. This study aimed to evaluate the prescriptions that presented illegibility, as well as their origin, their classification and their main filling errors. The project was approved by the Ethics Committee. The survey was conducted in one of the establishments of pharmacies PagueMenos® Network, during the month of June 2015, which analyzed 200 recipes considered unreadable. Of the recipes analyzed, 43 (22%) did not allow the dispensing of the drug. It was also found that most recipes were coming from public institutions (60%) and that 74% were prescriptions of Special Control. Furthermore, there is the absence of significant information on prescriptions, as duration of treatment, dosage, date. Thus, these features prove that illegibility is a recurring practice that prevents a safe drugs dispensing in health facilities and proves the importance of standardization of recipes allowing treatment effectiveness.

Influence of light intensity, fertilizing and season on the cirsiliol content, a chemical marker of Leonotis nepetifolia (Lamiaceae).

BACKGROUND: Leonotis nepetifolia (Family Lamiaceae) is a medicinal plant from which the flavonoid cirsiliol with sedative, hypnotic, anti-inflammatory and cytotoxic activity has been extracted. METHODS: Seedlings were cultivated under different levels of shade in native or fertilized modes. The content of cirsiliol was measured monthly by high-performance liquid chromatography and the total phenolic content by the Folin-Ciocalteu method. Monitoring of growth was carried out with the weekly measurement of height until the stabilization of growth. RESULTS: The application of fertilizing and/or shading does not alter significantly the cirsiliol content. However, this content varies throughout the year, reaching the peak production in the summer, independently of the treatment applied. This same profile, with production in the summer, was also verified for phenolic compounds, reaching 58.15 ± 9.35 mg of equivalents of gallic acid per g of extract in the summer, content 1.84 times greater than the content verified in winter (31.56 ± 4.09 mg of gallic acid/g of extract). Although shading and fertilizing had no effect on cirsiliol content, the results also showed a positive influence on the height and biomass of the plant, which can causes a higher yield of extractable material. DISCUSSION: Biotic and abiotic stresses are able to increase or decrease the production of secondary metabolites, including phenolic compounds in medicinal plants and, as the stress response is peculiar to each species, cultivation studies become necessary. The present study reports by the first time the influence of shading, fertilizing and seasons in cirsiliol content in L. nepetifolia. Among analyzed variables, the seasons showed a larger influence in expression of cirsiliol and among seasons, our results showed that the summer is the ideal season for collections. In summer, the photoperiod is larger than in other seasons of the year and due to that, the plants need greater protection against the long photoperiod. For this, the plants increase the production of phenolic compounds as observed in this study. Although they do not influence the production of cirsiliol, the shading and nutrients in soil favor growth and leaf area of several plants, explaining, thus, the higher height and biomass obtained.

Phytochemical and pharmacological aspects of Cnidoscolus Pohl species: A systematic review.

BACKGROUND: Cnidoscolus is a genus belonging to the Euphorbiaceae family, distributed in South American countries, such as Mexico and Brazil, which includes several species widely used in folk medicine. However, the genus is not sufficiently exploited from a chemical and pharmacological point of view. HYPOTHESIS/PURPOSE: This paper aims to present a systematic review of known pharmacological and chemical aspects from Cnidoscolus, an important genus for South America research groups on medicinal plants. In this article, we highlight the importance of Cnidoscolus species in the search for new bioactive molecules. STUDY DESIGN: A systematic review was conducted in order to collect chemical and pharmacological information on species of this genus in the last 25 years. METHODS: Literature search was performed through specialized databases (PUBMED, LILACS, SCIELO, Science Direct and Web of Science) using different combinations of the following keywords: Cnidoscolus, phytochemistry, pharmacological activity. For the selection of the manuscripts, two independent investigators (RGOJ and CAAF) first selected the articles according to the title, then to the abstract and finally through an analysis of the full-text publication. All selected manuscripts were analyzed for year of publication, country where the research was performed, reported plant species, isolated chemical compounds and evaluated biological activities. RESULTS: Most of the studies involving Cnidoscolus were conducted by research groups located in Brazil, Nigeria and Mexico. Regarding the annual evolution of the publications, a larger number of articles published in 2014 were observed. Flavonoids, triterpenes and diterpenes represent the main classes of secondary metabolites that have been isolated from Cnidoscolus. In terms of the pharmacological investigations, C. aconitifolius, C. chayamansa and C. quercifolius are considered the most studied species, with different pharmacological activities. CONCLUSION: All findings indicate that Cnidoscolus is an important genus of the Euphorbiaceae family. However, considering its chemical and pharmacological importance, the studies developed with Cnidoscolus species are still limited, representing an opportunity to investigate new bioactive molecules.