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.

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.

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.

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.

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.

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.

Development and Evaluation of Photoprotective O/W Emulsions Containing Hydroalcoholic Extract of Neoglaziovia variegata (Bromeliaceae).

Neoglaziovia variegata is a Bromeliaceae plant species widely found in Brazil with several pharmacological properties, including photoprotective activity. Although herbal-based active ingredients have been applied in cosmetic products, especially for skin treatment, its application in sunscreen formulations remains unexplored. The aim of this work is to evaluate the photoprotective effect of cosmetic formulations containing hydroalcoholic extract of N. variegata (Nv-HA). Initially, the phenolic and flavonoid total content of Nv-HA were determined. The photoprotective activity of Nv-HA was subsequently assessed using a spectrophotometric method. Nv-HA was incorporated in O/W emulsions in the presence or absence of synthetic filters and their photoprotective efficacy was evaluated by spectrophotometric SPF determination. Finally, the stability study of the formulations was performed through the freezing/defrosting method. Nv-HA showed significant phenolic and flavonoids content (61.66 ± 5.14 mg GAE/g and 90.27 ± 5.03 mg CE/g, resp.). Nv-HA showed SPF values of 5.43 ± 0.07 and 11.73 ± 0.04 for the concentrations of 0.5 and 1.0% (v/v), respectively. It was verified that Nv-HA potentiated the photoprotective effect of formulations containing only synthetic filters. Furthermore, the formulations have remained stable at the end of the preliminary stability study. According to the results, it was concluded that Nv-HA can be used as a chemical filter in cosmetic formulations.

Development and Evaluation of Stability of a Gel Formulation Containing the Monoterpene Borneol.

Borneol is a bicyclic monoterpenoid alcohol commonly used in traditional Chinese and Indian medicine. It is extracted from the essential oil of various medicinal plants. It has antibacterial, analgesic, and anti-inflammatory action proven in studies that used oral and intraperitoneal applications of this monoterpene in mice. The current study was designed to develop a topical gel formulation containing the monoterpene borneol using carbopol as gel base and to evaluate its stability. The prepared formulation was subjected to physical characterization and physical-chemistry assessment. The gel was prepared from carbopol and 5% of borneol. The prepared gel was subjected to pharmacotechnical tests such as its pH, viscosity, conductivity, spreadability, centrifugation, and accelerated stability with freezing-thaw cycle. The borneol was successfully incorporated into the carbopol formulation. Borneol gel (BG5) showed good stability after eight months of its development and after 12 days in the freeze-thaw cycle, not showing statistical difference in pH value, conductivity, and viscosity before and after test. Furthermore, the formulation showed a good spreadability. Therefore, it was concluded that the formulation could be very promising alternative for the topical or transdermal treatment of skin diseases.

Estado da arte de Bauhinia forficata Link (Fabaceae) como alternativa terapêutica para o tratamento do diabetes melittus / Bauhinia forficata Link (Fabaceae) as alternativetherapy in the treatment of diabetes mellitus

O Diabetes mellitus, por tratar-se de uma doença crônica e por apresentar um crescimento acentuado na sociedade brasileira, tornou-se alvo da comunidade científica na busca de novas alternativas terapêuticas. Diversos estudos estão sendo desenvolvidos com o objetivo de comprovar as aparentes propriedades farmacológicas de espécies vegetais empregadas no tratamento desta enfermidade. Sendo assim, a Bauhinia forficata Link, comumente conhecida como pata-de-vaca, figura entre as espécies mais utilizadas para esse fim. Dentre os representantes de Bauhinia, a que apresenta maior número de estudos referentes à atividade hipoglicemiante e antidiabética é a espécie referida. Isto, pois, devido as suas atividades farmacológicas, diversos estudos relatam seus aspectos botânicos, composição química e eficácia. Esse constante interesse em seu estudo se mostra imperioso para sua utilização de forma segura e eficaz, possibilitando o desenvolvimento de formas farmacêuticas para o tratamento de diabetes.

Diabetes mellitus is a chronic disease with an ever-increasing incidence in Brazil and has become the object of scientific research into the search for novel therapeutic alternatives. A number of studies have been developed to demonstrate the pharmacological properties of plant species employed in folk medicine for the treatment of this disease. One such plant is the Brazilian white orchid tree, Bauhinia forficate Link, known locally as pata-de-vaca [cow foot]. Among representatives of the genus Bauhinia, this species has the greatest number of studies addressing its botanical aspects, chemical composition and effectiveness in terms of hypoglycemic and anti-diabetic activity. Studies on this plant are important to the safe, effective development of pharmaceutical products for the treatment of diabetes.

Caracterização fitoquímica e físico-química das folhas de Bauhinia forficata Link coletada em duas regiões brasileiras / Phytochemical characterization and physical chemistry from the leaves of Bauhinia forficata Link collected in two brazilian regions

Folhas da espécie vegetal Bauhinia forficata Link, popularmente conhecida como pata de vaca, apresentam amplo potencial terapêutico no tratamento do diabetes mellitus. Amostras desta espécie vegetal, obtidas em duas regiões do Brasil (Minas Gerais e Paraná), foram submetidas à caracterização fitoquímica e físico-química (granulometria, perda por dessecação, teor de cinzas e teor de extrativos) para realização de um estudo comparativo entre indivíduos cultivados em regiões distintas, bem como estabelecimento de especificações para seu controle de qualidade. Para a caracterização fitoquímica, extratos metanólicos das amostras foram avaliados através de cromatografia de camada delgada (CCD) para pesquisa das principais classes de metabolitos secundários. Enquanto que, para as análises físico-químicas foram adotadas metodologias farmacopeicas. A análise estatística dos dados realizou-se através dos testes F de Fischer e t de Student. De acordo com a avaliação fitoquímica foi possível observar um perfil similar para ambas as amostras com presença dos seguintes grupos: flavonóides, proantocianidinas, leucoantocianidinas, triterpenos, esteróides, açúcares redutores, além de substâncias antioxidantes com bandas coincidentes às dos compostos flavonoídicos. Por outro lado, as amostras apresentaram algumas propriedades físico-químicas diferentes tais como granulometria e umidade residual em virtude da origem e do processamento adotados pelos fornecedores. Já os valores do teor de cinzas mostraram-se dentro das especificações e não foi observada diferença significativa para o teor de extrativos. Os resultados obtidos neste trabalho contribuíram no processo de identificação e padronização de parâmetros de qualidade para as folhas de B. forficata.

Leaves of the plant species Bauhinia forficata Link, popularly known as pata de vaca, have broad therapeutic potential in treating diabetes mellitus. Aiming to establish specifications for quality control of the specie, samples of plant material obtained from two regions of Brazil (Minas Gerais and Paraná), were subjected to phytochemical and physicochemical characterization (grain size, loss on drying, ash content and extractives). For phytochemical characterization, methanolic extracts of samples were evaluated by thin layer chromatography (TLC) to search the main classes of secondary metabolites. While for the physicochemical analyses were followed Pharmacopoeic procedures. The statistical analysis was performed using the Fisher F test and Student t test. According to phytochemical evaluation was observed one similar profile for both samples with the presence of following groups: flavonoids, proanthocyanidins, leucoanthocyanidins, triterpenes, steroids, sugars, and antioxidants with similar bands of flavonoid compounds. On the other hand, the samples showed some different physicochemical properties such as particle size and content residual moisture because of the origin and processing adopted by suppliers. In turn the values of ash showed to be within specifications and there was no significant difference in the extractive content. The results of this work contributed to the process of identification and standardization of quality parameters for the leaves of B. forficata

A própolis no combate a tripanossomatídeos de importância médica: uma perspectiva terapêutica para doença de chagas e leishmaniose / Propolis activity against trypanosomatids of medical relevance: a therapeutic perspective for chagas disease and leishmaniasis

Protozoonoses tais como leishmaniose e doença de Chagas, consideradas doenças negligenciadas, afetam milhões de pessoas em todo o mundo, por isso são constantes as pesquisas para o desenvolvimento de terapias mais eficazes. O interesse pela fitoterapia como fonte alternativa para o tratamento de inúmeras enfermidades tem crescido e merece destaque o uso da própolis, amplamente utilizada na prática médica popular. São atribuídas à própolis, principalmente às variedades encontradas no Brasil, diversas propriedades farmacológicas por sua complexa composição. Estudos in vivo e in vitro com extratos de própolis contra Trypanosoma cruzi e Leishmania vêm sendo realizados nos últimos anos com resultados promissores, embora sejam necessários estudos complementares. Este trabalho traz uma revisão sobre os aspectos clínicos e epidemiológicos da leishmaniose e doença de Chagas, assim como a aplicabilidade da própolis como um recurso terapêutico eficaz e seguro para o tratamento dessas protozoonoses.

A preformulation study of a new medicine for Chagas disease treatment: physicochemical characterization, thermal stability, and compatibility of benznidazole.

This work aimed the studies of physicochemical characterization, thermal stability, and compatibility of benznidazole (BNZ) drug by spectroscopy (NMR, IR), thermoanalytical (differential thermal analysis, differential scanning calorimetry, and thermogravimetry), and chromatographic (HPLC) techniques, beyond the analytical tools of Van't Hoff equation and Ozawa model. The compatibility study was conducted by binary mixtures (1:1, w/w) of the drug with microcrystalline cellulose 102 and 250, anhydrous lactose, and sodium starch glycolate. The physicochemical characterization confirmed data reported in scientific literature, guaranteeing authenticity of the analyzed raw material. The drug melts at 191.68°C (∆H, 119.71 J g(-1)), characteristic of a non-polymorphic raw material, and a main stage decomposition at 233.76-319.35°C (∆m, 43.32%) occurred, ending the study with almost all mass volatilized. The quantification of drug purity demonstrated a correlation of 99.63% between the data obtained by chromatographic (99.20%) and thermoanalytical technique (99.56%). The Arrhenius equation and Ozawa model showed a zero-order kinetic behavior for the drug decomposition, and a calculated provisional validity time was 2.37 years at 25°C. The compatibility study evidenced two possible chemical incompatibilities between BNZ and the tested excipients, both associated by the authors to the reaction of the BNZ's amine and a polymer carbohydrate's carbonile, being maillard reactions. The BNZ reaction with anhydrous lactose is more pronounced than with the sodium starch glycolate because the lactose has more free hydroxyl groups to undergo reduction by the drug. In this sense, this work guides the development of a new solid pharmaceutical product for Chagas disease treatment, with defined quality control parameters and physicochemical stability.

Obtenção de comprimidos contendo cálcio de conchas de ostras: pré-formulação e liodisponibilidade comparativa / Obtaining tablets with calcium from oyster shells: preformulation and comparative lyoavailability

A osteoporose é uma doença que afeta um número significativo de pessoas no mundo todo, em especial nos países subdesenvolvidos. Nesse contexto, o pó de concha de ostra, que constitui uma fonte de cálcio, aparece como uma oportunidade de utilizar os recursos naturais da região litorânea brasileira, na suplementação alimentar de sua população. O estudo se propôs a aproveitar essa fonte natural de cálcio, incorporando-a na forma farmacêutica comprimido. O estudo foi desenvolvido em duas etapas, a primeira com a otimização da matéria-prima a partir de conchas de ostra, desde o processo de seleção até a transformação da concha de ostra em pó, com caracterização físico-química e pré-formulação desse pó. A segunda etapa foi a obtenção dos comprimidos desde o desenvolvimento até os ensaios de liodisponibilidade comparativa. Os estudos de pré-formulação e o planejamento fatorial dos excipientes (aglutinante, lubrificante e desintegrante) permitiram obter com economia e performance comprimidos com liodisponibilidade semelhante à referência Os-cal®.

Osteoporosis is a disease that affects a significant number of people in the world, particularly in developing countries. In this context, the powder of oyster shells, found to be a calcium source, emerges as one opportunity to use the natural resources from the Brazilian coast region for alimentary supplementation. This study proposes the use of this natural source of calcium, incorporated in tablets. The study was developed in two parts. The first was concerned with optimizing the raw material from oyster shells, from the selection process until the transformation of de oyster shell into dust; and with the physicochemical evaluation and preformulation of this dust. The second part consisted of obtaining tablets, from the development until the comparative evaluation of lyoavailability. The studies on preformulation and factorial planning of the excipients (binging agent, levigating agent and disintegrants) have made possible to obtain tables with a similar lyoavailability, in terms of economy and performance, to the medicine reference Os-cal®.