The use of natural extracts with photoprotective activity: a 2015-2023 patent prospection.

Synthetic sunscreen offers protection against excessive exposure to ultraviolet (UV) radiation from the sun, and protects the skin from possible damage. However, they have low efficacy against the formation of reactive oxygen species (ROS), which are highly reactive molecules that can be generated in the skin when it is exposed to UV radiation, and are known to play a role in oxidative stress, which can contribute to skin aging and damage. Thus, there is an ongoing search for sunscreens that do not have these negative effects. One promising source for these is natural products. Therefore, the current patent review summarizes topical formulations made from natural compounds that have antioxidant properties and can be used as photoprotective or anti-aging agents, either using a single natural extract or a combination of extracts. The review reports basic patent information (applicant country, type of applicant, and year of filing) and gives details about the invention, including its chemical composition, and the in vitro and in vivo tests performed. These patents describe natural products that can be used to protect the skin and validate their efficacy, and safety, in addition to standardizing their formulations. The compositions described illustrate the consistent innovation in the use of natural products to protect against UV damage and photoaging disorders, a promising field which is receiving growing global recognition.

Plant-based compositions for the treatment of local and topical bacterial infections: a patent review.

Aim: To examine recent patents related to plants with antimicrobial effects. Methods: Our investigation was carried out using the Espacenet database, searching patents related to International Patent Classification (IPC) codes A61P31/04, and A61K36/00 between 2008 and 2023. Results: The study began with 360 patents, of which 15 were found to be duplicates; 144 were not related to the research topic and six were not available. Then, 48 patents were related to other administration routes. The final selection was 47 patents related to local administration compositions. The potential for these herbal compositions to be marketed as over-the-counter medicines was evident. Conclusion: Developing new plant-origin anti-infective agents could provide promising solutions for combating resistant infections and offer accessible treatment options.

[Box: see text].

New molecules of importance in the prevention and treatment of acne: A systematic patent review (2016-2020).

BACKGROUND: Acne is a highly prevalent disease that mainly affects the pilosebaceous units associated with sebaceous glands, causing inflammatory skin lesions and affecting the self-esteem, mental health, and quality of life of those who suffer from this disease. Different treatments exist today to prevent, reduce, and improve symptoms; however, over the years, there have been problems with bacterial resistance and slight effectiveness with prolonged use. OBJECTIVE: The purpose of this article is based on the review of patents of new products of principal topical administration for the treatment of acne in recent years 2016-2020, to evaluate and analyze novel synthetic molecules and semi-synthetics with potential therapeutic and preventive in the acne treatment. METHODS: A systematic review of patents was conducted through the official database of the European Patent Office - Espacenet, where the search focused on the keywords: "acne and bacteria" in the title or abstract. Only patents granted between the years 2016-2020 were included, with products having molecules with a synthetic and semi-synthetic origin, without considering natural, biological products or those used as diagnostic means. RESULTS: A total of 19 patents were selected, most with principally antimicrobial and anti-inflammatory action, where the reduction in the appearance of resistance by C. acnes is verified, and its action is complemented by inhibiting the different pathophysiological mechanisms that lead to the worsening of the disease. CONCLUSION: Novel approaches in the treatment and prevention of acne, mainly topically, are focused on the reduction of bacterial resistance and irritation compared to current treatments. The use of combined formulations provides better results with additional benefits, improving treatment times and patient adherence.

Modeling and Simulation as a Tool to Assess Voriconazole Exposure in the Central Nervous System.

Voriconazole is a triazole antifungal used empirically for the treatment of complicated meningitis associated with Cryptococcus neoformans. Biopsy studies show that the drug exhibits adequate brain penetration although levels of cerebral spinal fluid (CSF) are highly variable. Considering that CSF is one of the main surrogates for CNS exposure, the present work proposed the building of a population pharmacokinetic modeling (popPK) model able to describing the exposure achieved by voriconazole in the plasma, interstitial cerebral fluid and CSF of healthy and infected rats. The developed popPK model was described by four compartments, including total plasma, free brain and total CSF concentrations. The following PK parameters were determined: Km = 4.76 mg/L, Vmax = 1.06 mg/h, Q1 = 2.69 L, Qin = 0.81 h-1 and Qout = 0.63 h-1. Infection was a covariate in the Michaelis-Menten constant (Km) and intercompartmental clearance from the brain tissue compartment to central compartment (Qout). Simulations performed with the popPK model to determine the probability of reaching the therapeutic target of fAUC > MIC showed that VRC has sufficient tissue exposure in the interstitial fluid and in the CSF for the treatment of fungal infections in these tissues at prevalent minimum inhibitory concentrations.

Fruits as nutraceuticals: A review of the main fruits included in nutraceutical patents.

Fruits have relevant usefulness in the elaboration of nutraceutical compositions and, as it is considered a "natural medicine", its market has been growing exponentially each year. Fruits, in general, contain a large source of phytochemicals, carbohydrates, vitamins, amino acids, peptides and antioxidants that are of interest to be prepared as nutraceuticals. The biological properties of its nutraceuticals can range from antioxidant, antidiabetic, antihypertensive, anti-Alzheimer, antiproliferative, antimicrobial, antibacterial, anti-inflammatory, among others. Furthermore, the need for innovative extraction methods and products reveals the importance of developing new nutraceutical compositions. This review was developed by searching patents of nutraceuticals from January 2015 until January 2022 in Espacenet, the search database of the European Patent Office (EPO). Of 215 patents related to nutraceuticals, 43% (92 patents) were including fruits, mainly berries. A great number of patents were focused on the treatment of metabolic diseases, representing 45% of the total patents. The principal patent applicant was the United States of America (US), with 52%. The patents were applied by researchers, industries, research centers and institutes. It is important to highlight that from 92 fruit nutraceutical patent applications reviewed, 13 already have their products available on the market.

New Technologies to Diagnose and Treat a Multidrug-Resistant Candida auris: A Patent Review.

Candida auris is responsible for hospital outbreaks worldwide. Some C. auris isolates may show concomitant resistance to azoles, echinocandins, and polyenes, thereby possibly leaving clinicians with few therapeutic options. In addition, this multi-drug-resistant yeast is difficult to identify with conventional methods and has the ability to persist on environmental surfaces causing hospital-acquired infections. The development of new treatment options and tools for identification is critical to control, prevent, and establish an early diagnosis of this emerging pathogen. The aim of this study was to perform a critical patent review to explore and identify the latest advances in therapeutic strategies as well as diagnostic methods for C. auris. A total of 19 patents were identified for a preliminary assessment from the Espacenet database. Three patents were excluded as they were out of focus for this review according to their abstract and/or description. The final selection covered 16 patents, which were surveyed by country, year and classified as treatment or diagnostic methods for C. auris. As noted in the patent reading, in recent years, the interest of academic, government and industry sectors have shown an increasing tendency focused on research and development of new therapeutic molecules and diagnostic methods to combat this emerging pathogen.

Pharmacokinetic/Pharmacodynamic Modeling and Application in Antibacterial and Antifungal Pharmacotherapy: A Narrative Review.

Pharmacokinetics and pharmacodynamics are areas in pharmacology related to different themes in the pharmaceutical sciences, including therapeutic drug monitoring and different stages of drug development. Although the knowledge of these disciplines is essential, they have historically been treated separately. While pharmacokinetics was limited to describing the time course of plasma concentrations after administering a drug-dose, pharmacodynamics describes the intensity of the response to these concentrations. In the last decades, the concept of pharmacokinetic/pharmacodynamic modeling (PK/PD) emerged, which seeks to establish mathematical models to describe the complete time course of the dose-response relationship. The integration of these two fields has had applications in optimizing dose regimens in treating antibacterial and antifungals. The anti-infective PK/PD models predict the relationship between different dosing regimens and their pharmacological activity. The reviewed studies show that PK/PD modeling is an essential and efficient tool for a better understanding of the pharmacological activity of antibacterial and antifungal agents.

Recent Progress in Self-Emulsifying Drug Delivery Systems: A Systematic Patent Review (2011-2020).

Self-emulsifying drug delivery systems (SEDDS) are lipid-based isotropic mixtures that enhance the bioavailability of poorly water-soluble drugs and reduce the possible side effects, offering a wide variety of treatments for several pathologies. The aim of this review is to discuss the state of the art of patents for this drug delivery system by studying recent patent applications (2011 to 2020). We performed a thorough screening using the European Patent Office's Espacenet database, from which 37 inventions were selected and fully studied. China had more patent applications, and the articles published about SEDDS exceeds both in number and technological advance the submitted inventions. Nevertheless, the patents presented herein are innovative to address known issues to traditional SEDDS, including storage and formulation stability, solid formulations, acute gastrointestinal toxicity from surfactants, and drug delivery through alternative routes of administration. This study also revealed that release behavior for SEDDS and associated pharmacokinetics were not completely disclosed by the inventors of the patents and that further studies are required.

Natural Products as Outstanding Alternatives in Diabetes Mellitus: A Patent Review.

Diabetes mellitus (DM) is a metabolic syndrome that can be considered a growing health problem in the world. High blood glucose levels are one of the most notable clinical signs. Currently, new therapeutic alternatives have been tackled from clinicians' and scientists' points of view. Natural products are considered a promising source, due to the huge diversity of metabolites with pharmaceutical applications. Therefore, this review aimed to uncover the latest advances in this field as a potential alternative to the current therapeutic strategies for the treatment of DM. This purpose is achieved after a patent review, using the Espacenet database of the European Patent Office (EPO) (2016-2022). Final screening allowed us to investigate 19 patents, their components, and several technology strategies in DM. Plants, seaweeds, fungi, and minerals were used as raw materials in the patents. Additionally, metabolites such as tannins, organic acids, polyphenols, terpenes, and flavonoids were found to be related to the potential activity in DM. Moreover, the cellular transportation of active ingredients and solid forms with special drug delivery profiles is also considered a pharmaceutical technology strategy that can improve their safety and efficacy. From this perspective, natural products can be a promissory source to obtain new drugs for DM therapy.

Recent patent applications in beverages enriched with plant proteins.

Recently, many consumers have been adding plant-based beverages to their diets, due to different reasons. The addition of plant proteins to enrich these products in order to make them more nutritionally balanced has become a trend, mainly because of their lower prices and reduced environmental damage. Thus, the aims of the present patent review are to discuss the potential of, and challenges posed by, plant proteins to the beverage industry, as well as to check market trends, focused on raw materials and beverage types. Based on the results, pea, rapeseed, bean, peanut, chickpea, lentil, hempseed, sunflower seed, and cottonseed were among the most often addressed raw materials. Furthermore, this enrichment process is not limited to create products that mimic dairy, therefore expansion in plant proteins used to enrich carbonated beverages, sports drinks, or even juices is expected to happen. Thus, plant-derived proteins have been promising to high-quality beverage production, as well as to ensure food security, animal welfare, and low environmental impacts.

What's New in Allergen Immunotherapy Patents? A Review.

In recent years, allergies are on the rise. The growth of allergies cases has changed the immune system's response to new pathogens. The therapy used to treat these diseases is based on allergen avoidance, pharmacotherapy and allergen-specific immunotherapy. The last one has received a lot of interest in the research field, due to the possibility of leading the patient to a cure. In this sense, new allergen immunotherapy need to be developed or improved to increase safety and efficiency. This review aims to evaluate patents published, from 2015 to July 2020, that have developed allergic immunotherapy treatment and administration routes, as well as new alternatives of vehicles, carriers and delivery systems in this context. The advance of new patents has been mostly seen in China and United States. The oral route is the most used in the development of new allergy treatments. However, due to the challenges that still exist in allergy therapy, association with other pathways is interesting to amplify the possibilities and alternatives of treatment. Thus, other routes of administration for allergen-specific immunotherapy such as topical, sublingual and intranasal have been explored in the research and industrial fields. Nevertheless, it has been observed that few studies are using these alternative administration routes, probably due to the higher cost and lack of investments. The delivery systems are also other tools that can be more explored in the allergen immunotherapy formulations. The effectiveness, safety and acceptance of this therapy depends on the development of new formulations and routes of administration.

Regulatory aspects and evidences of melatonin use for sleep disorders and insomnia: an integrative review.

BACKGROUND: Insomnia is a sleep disorder characterized by difficulty of falling asleep or maintaining sleep, which affects different age groups. Currently, melatonin is used as a therapeutic treatment in cases of insomnia in children, adults, and elderly people. OBJECTIVE: To evaluate the effectiveness of melatonin in sleep disorders, its dosage, potential adverse effects, as well as labeling laws and regulations in Brazil. METHODS: This integrative review was carried out using the Cochrane Library, Medline (Pubmed), and Science Direct databases. Twenty-five articles and three documents available on the Brazilian Society of Endocrinology and Metabology (SBEM) and National Health Surveillance Agency (ANVISA) websites published between 2015 and 2020 were selected to be evaluated in full. RESULTS: It was found that in most of the selected articles the use of melatonin reduces sleep latency. The effective melatonin doses varied according to each age group, from 0.5 to 3 mg in children, 3 to 5 mg in adolescents, 1 to 5 mg in adults, and 1 to 6 mg in elderly people. Side effects are mild when taking usual doses. In Brazil, no registered drug and current regulation on the use and marketing of melatonin has been identified. CONCLUSION: The use of melatonin is an alternative therapy that can be used for sleeping disorders. According to the evidences found, it did not demonstrate toxicity or severe side effects, nor dependence even when administered at high doses, suggesting that it is a safe medication to treat patients of different ages suffering from sleeping disorders.

Regulatory aspects and evidences of melatonin use for sleep disorders and insomnia: an integrative review / Aspectos regulatórios e evidências do uso de melatonina em distúrbio do sono e insônia: uma revisão integrativa

ABSTRACT Background: Insomnia is a sleep disorder characterized by difficulty of falling asleep or maintaining sleep, which affects different age groups. Currently, melatonin is used as a therapeutic treatment in cases of insomnia in children, adults, and elderly people. Objective: To evaluate the effectiveness of melatonin in sleep disorders, its dosage, potential adverse effects, as well as labeling laws and regulations in Brazil. Methods: This integrative review was carried out using the Cochrane Library, Medline (Pubmed), and Science Direct databases. Twenty-five articles and three documents available on the Brazilian Society of Endocrinology and Metabology (SBEM) and National Health Surveillance Agency (ANVISA) websites published between 2015 and 2020 were selected to be evaluated in full. Results: It was found that in most of the selected articles the use of melatonin reduces sleep latency. The effective melatonin doses varied according to each age group, from 0.5 to 3 mg in children, 3 to 5 mg in adolescents, 1 to 5 mg in adults, and 1 to 6 mg in elderly people. Side effects are mild when taking usual doses. In Brazil, no registered drug and current regulation on the use and marketing of melatonin has been identified. Conclusion: The use of melatonin is an alternative therapy that can be used for sleeping disorders. According to the evidences found, it did not demonstrate toxicity or severe side effects, nor dependence even when administered at high doses, suggesting that it is a safe medication to treat patients of different ages suffering from sleeping disorders.

RESUMO Antecedentes: Insônia é um distúrbio do sono caracterizado por dificuldade de iniciar e manter o sono, afetando diferentes faixas etárias. Atualmente, a melatonina é utilizada no tratamento de insônia em crianças, adultos e idosos. Objetivo: Avaliar a eficácia da melatonina nos distúrbios do sono, posologia e potenciais efeitos adversos, bem como a regulamentação vigente no Brasil. Métodos: Trata-se de uma revisão integrativa, os artigos foram identificados nas bases de dados Cochrane Library, Medline (Pubmed) e Science Direct, totalizando 25 artigos, e foram selecionados três materiais disponíveis no site da Sociedade Brasileira de Endocrinologia e Metabologia e Agência Nacional de Vigilância Sanitária, publicados entre 2015 e 2020. Resultados: Verificou-se na maioria dos artigos selecionados que a melatonina reduz a latência do sono. Quanto as dosagens de melatonina identificou-se variação em cada faixa etária, para crianças de 0,5 a 3mg; adolescentes de 3 a 5mg; adultos de 1 a 5mg e idosos 1 mg a 6 mg demostraram serem eficazes. Em doses habituais os efeitos colaterais são leves. No Brasil, não foi identificado medicamento registrado e regulamentação vigente sobre o uso e comercialização de melatonina. Conclusão: A utilização da melatonina é uma alternativa que pode ser utilizada em distúrbios do sono. De acordo com as evidências encontradas, não demonstrou toxicidade ou efeitos colaterais severos, nem dependência mesmo em doses elevadas, sendo, portanto, segura para tratamento de pacientes desde crianças a idosos que sofrem de distúrbios do sono.

A patent review of antibiofilm fungal drugs (2002-present).

Fungal biofilms, such as Candida albicans biofilms, are capable of surviving in hostile environments owing to their remarkable ability to adhere to surfaces and their tolerance to chemical interventions. Currently, therapeutic treatment options are few, making these biofilm-based infections problematic particularly due to their great tolerance to conventional antimicrobial drugs, thus causing serious health and economic problems. Therefore, the development of new drugs and antibiofilm specific therapies for the prevention and treatment of antifungal to eradicate biofilms are needed. This study was aimed at carrying out a patent review analysis to identify the innovation trends, and to explore the latest antifungal drugs and the specific therapeutic strategies available for the treatment of fungal biofilms. The present patent review was carried out using the Espacenet database, using the key words "biofilm and antifungal," from 2002 to December 2019. Through this review, it was possible to identify that most of the patent contents refer to new synthetic drugs derived from natural products and associations thereof with existing antifungal drugs. Methods and biomaterials for the treatment and prevention of fungal biofilms, mainly for C. albicans biofilms, which is the most isolated and studied fungal species, were also disclosed. The lack of scientific and technical information on the biofilm eradication subject is remarkable and further confirmed by the small number of patents identified in this survey.

Oficinas profissionalizantes para reinserção de internos de um centro terapêutico de toxicômanos no mercado de trabalho / Professional workshops for reinsertion of internal staff from a drug rehabilitation center in the labor market / Cursos profesionales para la reinserción de internos de un centro terapéutico de toxicómanos en el mercado laboral

Objetivo: desenvolver atividades a fim de facilitar a reinserção social e no mercado de trabalho de dependentes químicos residentes da comunidade terapêutica Fazenda Paraíso, um centro de recuperação de toxicômanose alcoólatras do noroeste do estado do Rio Grande do Sul. Método: trata-se de um estudo de abordagem qualiquantitativa, com caráter descritivo. Quinze internos com idade entre 16 e 49 anos participaram de oficinas com cunho teórico/prático ministradas por docentes e acadêmicos do curso de graduação de Farmácia. Resultados: a maioria dos participantes estava com idade acima dos 30 anos, e 80% tinham somente formação em educação básica. Constatou-se que o emprego é capaz de gerar estabilidade financeira, além de proporcionar dignidade e trazer reconhecimento por parte da sociedade, sendo então importante para o toxicômano. Conclusão: o profissional farmacêutico pode ser um grande aliado na reinserção do dependente químico na sociedade, seja pela ministração de oficinas ou palestras de educação em saúde

Objective: to develop activities that facilitate social and labor market reintegration of drug addicts residing in Fazenda Paraíso, a drug and alcohol rehabilitation center in the northwest of Rio Grande do Sul, Brazil. Methods: this qualitative/quantitative study of descriptive character included 15 interns aged 16 to 49 years who participated in workshops of theoretical/practical nature taught by educators of the Pharmacy graduation course. Results: most participants were over 30 years old, and 80% had only basic education. Employment was shown to allow for financial stability, as well as to provide dignity and recognition by society, and it is considered important for drug addicts. Conclusion: pharmacy professionals can be great allies in the reintegration of drug addicts in society by providing workshops or lectures on health education

Objetivo: desarrollar actividades para facilitar la reinserción social y laboral de los toxicómanos que residen en la comunidad terapêutica Fazenda Paraíso, un centro para la recuperación de toxicómanos y alcohólicos en el noroeste del estado de Rio Grande do Sul. Método: estudio cualitativo y cuantitativo con carácter descriptivo. 15 pasantes de entre 16 y 49 años participaron en talleres teórico-prácticos impartidos por profesores y académicos del curso de graduación de Farmacia. Resultados: la mayoría de los participantes tenían más de 30 años, y el 80% solo tenían la educación básica. Se observó que el empleo es capaz de generar estabilidad financiera, además de proporcionar dignidad y reconocimiento por parte de la sociedad, lo cual es importante para el toxicómano. Conclusión: el profesional farmacéutico puede ayudar en la reintegración del toxicómano en la sociedad, por medio de la impartición de cursos o conferencias sobre la educación para la salud

Time-kill curves of daptomycin and Monte Carlo simulation for the treatment of bacteraemia caused by Enterococcus faecium.

OBJECTIVES: The aim of this study was to investigate the effect of daptomycin against vancomycin-resistant Enterococcus faecium bacteraemia using computer modelling. METHODS: Data obtained in vitro from time-kill curves were evaluated by PK/PD modelling and Monte Carlo simulations to determine the logarithmic reduction in the number of colony-forming units (CFU)/mL over 18 days of daptomycin treatment at 6, 8, and 10 mg/kg doses every 24 or 48 h and with variations in creatinine clearance (CLCR) of 15-29, 30-49, and 50-100 mL/min/1.73 m2. Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) for an area under the unbound drug concentration-time curve/minimum inhibitory concentration (fAUC/MIC) > 36 at the same doses and CLCR. RESULTS: Static time-kill model was employed to investigate the antibacterial efficacy of constant daptomycin concentrations. The time-kill curve analysis was performed using mathematical modelling based on a Hill coefficient factor. There was an expressive reduction (> 2 Log CFU/mL) over 18 days of daptomycin treatment in 75th percentile of individuals with CLCR of 15-100 mL/min/1.73 m2) with daptomycin 6-10 mg/kg/day, except for daptomycin every 48 h. Using fAUC/MIC > 36, PTA was > 90% at MICs ≤ 2 µg/mL. CONCLUSIONS: Higher daptomycin doses were associated with higher mortality in time-kill curves. The simulations indicated that independent of the CLCR the therapeutic responses of VRE occur with doses of daptomycin ≥ 6 mg/kg/day and daptomycin every 48 h is insufficient to treat enterococcal bacteraemia.

Uso de medicamentos potencialmente inapropriados para pessoas idosas em uma associação de aposentados / Use of potentially inappropriate medications by old people in a retiree's association

Resumo Objetivo verificar a prevalência da utilização de medicamentos potencialmente inapropriados e polifarmácia pela pessoa idosa. Método estudo observacional, com recorte transversal, analítico, quantitativo, de base populacional em uma associação de aposentados. Os dados foram coletados a partir de questionário estruturado, criado pelos próprios pesquisadores e aplicado em domicílio a uma amostra de 203 pessoas idosas. Resultados a idade média dos participantes foi de 73,1+8,13 anos (IC90%: 72,2-74,0), variando de 60 a 95 anos. A maioria declarou-se casado 54,2% (n=110/203), com ensino fundamental 71,4% (n=145/203), e renda familiar entre 2 e 4 salários mínimos 49,3% (n=100/203). As comorbidades mais encontradas foram: hipertensão arterial sistêmica 67,5% (n=137/203), artrite/artrose 30,5% (n=62/203), osteoporose 20,2% (n=41/203), entre outras. Quanto ao uso de medicamentos contínuos e eventuais, constatou-se uma mediana de 6 medicamentos utilizados pelos participantes, sendo 1 o número mínimo e 18 o número máximo. Houve polifarmácia em 64,5% (n=131/203) dos idosos e o uso de medicamentos potencialmente inapropriados em 78,8% (n=160/203). Quanto à utilização de polifarmácia, foi verificado associação significativa com: sexo feminino (p=0,004); e ter baixa escolaridade (p=0,017), e estado civil solteiro (0,027). Conclusão no âmbito da farmacoepidemiologia, o conhecimento dos fatores associados à utilização de medicamentos, como os identificados neste estudo, pode ser útil para alertar os prescritores e demais profissionais da saúde quanto à importância de identificar e monitorar os grupos mais vulneráveis, como por exemplo, as pessoas idosas.

Abstract Objective to verify the prevalence of the use of potentially inappropriate medications and polypharmacy by old people. Methods observational, cross-sectional, analytical, quantitative, population-based study in a retirees association. The data were collected from a questionnaire structured and created by the researchers and applied to the household. The association has 2,902 associates and underwent a stratified proportional sampling by gender, delimiting a sample of 203 old people, being 129 women and 76 men. Results the mean age of study participants was 73.1+8.13 years (90%CI:72.2-74.0), ranging from 60 to 95 years. The majority declared being married 110 (54.2%), with elementary education 145 (71.4%) and family income between 2 and 4 minimum wages 100 (49.3%). The most frequent comorbidities were: diabetes mellitus 33 (16.26%), systemic arterial hypertension 137 (67.49%), hypercholesterolemia 24 (11.8%), arthritis/arthrosis 62 (30.54%), osteoporosis 41 (20.2%), depression 27 (13.3%), among others with non-significant values. When analyzing the use of continuous and occasional medications, a median of 6 drugs used by participants was found, with 1 being the minimum number and 18 being the maximum number. The use of polypharmacy was identified in 131 (64.5%) old people and the use of potentially inappropriate medications in 160 (78.8%). Regarding the use of polypharmacy, a significant association was found with: female gender (p=0.004); and having low education (p=0.017), and single marital status (0.027). Conclusions in the context of pharmacoepidemiology, knowledge of the factors associated with the use of medicines may be useful to alert health professionals to the importance of identifying and monitoring the most vulnerable groups of old people in order to avoid the use of potentially inappropriate medications for the age group.

The Patenting and Technological Trends in Candidiasis Treatment: A Systematic Review (2014-2018).

BACKGROUND: In the last few decades, mycoses caused by opportunistic fungi namely Candida species has gained significant attention. Such infections are very common and present high mortality rates, especially in immunocompromised patients. Currently, a limited number of antifungal drugs are available for the treatment of these infections and are also often related to severe adverse side effects. Therefore, new drugs and innovative technologies for the treatment of this infection are necessary. OBJECTIVE: The aim of this study was to evaluate the development of new drugs, formulations, as well as patents for the treatment of infections caused by Candida spp. METHODS: The present patent review was carried out through a specialized search database Espacenet. The patent selection was based on the following inclusion criteria: Recent patents published in English or Spanish containing candidiasis as the keyword in the title, abstract or full text. This survey was conducted in October and November 2018. RESULTS: As a result of that, 22 patents were selected to the final selection, the most common routes of application were oral (n = 6), vaginal (n = 6), topical (n = 5) and others (n = 5). This fact is related to the clinical manifestations of candidiasis. CONCLUSION: Through this review, it was possible to identify significant improvements and advances in the area of antifungal therapeutic innovation research. In addition, we demonstrated the growing interest of academic and industrial groups in pharmaceutical development and novel formulations for the treatment of candidiasis. New therapeutic options can contribute to improve the quality of patient's life, prevent infections and promote the search for an innovative and effective treatment of Candida infections.

Population Pharmacokinetic Modeling to Describe the Total Plasma and Free Brain Levels of Fluconazole in Healthy and Cryptococcus neoformans Infected Rats: How Does the Infection Impact the Drug's Levels on Biophase?

PURPOSE: The present work aimed to evaluate the influence of experimental meningitis caused by C. neoformans on total plasma and free brain concentrations of fluconazole (FLC) in Wistar rats. METHOD: The infection was induced by the administration of 100 µL of inoculum (1.105 CFU) through the tail vein. Free drug in the brain was assessed by microdialisys (µD). Blood and µD samples were collected at pre-determined time points up to 12 h after intravenous administration of FLC (20 mg/kg) to healthy and infected rats. The concentration-time profiles were analyzed by non-compartmental and population pharmacokinetics approaches. RESULTS: A two-compartmental popPK model was able to simultaneously describe plasma and free drug concentrations in the brain for both groups investigated. Analysis of plasma and µD samples showed a better FLC distribution on the brain of infected than healthy animals (1.04 ± 0.31 vs 0.69 ± 0.14, respectively). The probability of target attainment was calculated by Monte Carlo simulations based on the developed popPK model for 125 mg/kg dose for rats and 400-2000 mg for humans. CONCLUSIONS: FLC showed a limited use in monotherapy to the treatment of criptoccocosis in rats and humans to value of MIC >8 µg/mL.