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.

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.

Nematode predatory ability of the fungus Duddingtonia flagrans affected by in vitro sequential exposure to ovine gastrointestinal tract.

Duddingtonia flagrans is a nematophagous fungus employed as a biocontrol agent of gastrointestinal nematodes in ruminants. After oral ingestion and passage through the digestive tract of animals, this microorganism captures the nematodes in the feces. The drastic conditions of ruminant digestive tract could affect fungi chlamydospores and therefore biocontrol activity. The aim of this study was to evaluate in vitro the effect of four ruminant digestive segments on the concentration and nematode predatory ability of a Colombian native strain of D. flagrans. The sequential four-step methodology proposed evaluated conditions of the oral cavity, rumen, abomasum, and small intestine such as pH (2, 6, 8), enzymes (pepsin, pancreatin), temperature (39 °C), and anaerobiosis comparing short (7 h) and long (51 h) exposure times. The results showed that the nematode predatory ability of the fungi is affected by sequential exposure to gastrointestinal segments and this effect depends on the exposure time to those conditions. After short exposure (7 h) through the four ruminant digestive segments, the fungi had a nematode predatory ability of 62%, in contrast, after long exposure (51 h) the nematode predatory ability was lost (0%). Moreover, the number of broken chlamydospores was higher in the long-exposure assay.

Extract of Calyces from Physalis peruviana Reduces Insulin Resistance and Oxidative Stress in Streptozotocin-Induced Diabetic Mice.

Diabetes mellitus is a metabolic disorder mainly characterized by obesity, hyperglycemia, altered lipid profile, oxidative stress, and vascular compromise. Physalis peruviana is a plant used in traditional Colombian medicine for its known activities of glucose regulation. This study aimed to evaluate the anti-diabetic activity of the butanol fraction from an extract of Physalis peruviana calyces in two doses (50 mg/kg and 100 mg/kg) in induced type 2 diabetic mice. Blood glucose levels were evaluated once a week, demonstrating that a dose of 100 mg/kg resulted in greater regulation of blood glucose levels in mice throughout the experiment. The same overall result was found for the oral glucose tolerance test (OGTT) and the homeostatic model assessment for insulin resistance (HOMA- IR). The lipid profile exhibited improvement compared to the non-treated group, a dose of 100 mg/kg having greater protection against oxidative stress (catalase, superoxide dismutase, and malondialdehyde levels). Histopathological findings in several tissues showed structure preservation in most of the animals treated. The butanol fraction from Physalis peruviana at 100 mg/kg showed beneficial results in improving hyperglycemia, lipidemia, and oxidative stress status, and can therefore be considered a beneficial coadjuvant in the therapy of diabetes mellitus.

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.

Matrix Effects of the Hydroethanolic Extract of Calyces of Physalis peruviana L. on Rutin Pharmacokinetics in Wistar Rats Using Population Modeling.

Rutin is the rutinose conjugate of quercetin. It presents several biological activities and is the major flavonoid in the hydroalcoholic extract of the calyces of Physalis peruviana L. It also shows hypoglycemic activity after oral administration. The aim of this work was to study the matrix effects of the extract from P. peruviana calyces on the pharmacokinetics of rutin and its metabolites in Wistar rats, using non-compartmental and population pharmacokinetic analyses. A pharmacokinetic study was performed after intravenous and oral administration of different doses of pure rutin and the extract. In the non-compartmental analysis, it was found that rutin from the extract exhibited higher distribution and clearance, as well as an 11-fold increase in the bioavailability of its active metabolites. A population pharmacokinetic model was also carried out with two compartments, double absorption and linear elimination, in which the extract and the doses were the covariates involved. This model correctly described the differences observed between rutin as a pure compound and rutin from the extract, including the dose dependency.

Matrix effects of the hydroethanolic extract and the butanol fraction of calyces from Physalis peruviana L. on the biopharmaceutics classification of rutin.

OBJECTIVES: The Biopharmaceutics Classification System (BCS) categorizes active pharmaceutical ingredients according to their solubility and permeability properties, which are susceptible to matrix or formulation effects. The aim of this research was to evaluate the matrix effects of a hydroethanolic extract of calyces from Physalis peruviana L. (HEE) and its butanol fraction (BF), on the biopharmaceutics classification of their major compound, quercetin-3-O-rutinoside (rutin, RU). METHODS: Rutin was quantified by HPLC-UV, and Caco-2 cell monolayer transport studies were performed to obtain the apparent permeability values (Papp ). Aqueous solubility was determined at pH 6.8 and 7.4. KEY FINDINGS: The Papp values followed this order: BF > HEE > RU (1.77 ± 0.02 > 1.53 ± 0.07 > 0.90 ± 0.03 × 10-5  cm/s). The lowest solubility values followed this order: HEE > RU > BF (2.988 ± 0.07 > 0.205 ± 0.002 > 0.189 ± 0.005 mg/ml). CONCLUSIONS: According to these results, rutin could be classified as BCS classes III (high solubility/low permeability) and IV (low solubility/low permeability), depending on the plant matrix. Further work needs to be done in order to establish how apply the BCS for research and development of new botanical drugs or for bioequivalence purposes.

Pharmacokinetics of Botanical Drugs and Plant Extracts.

BACKGROUND: Botanical drugs contain plant extracts, which are complex mixtures of compounds. As with conventional drugs, it is necessary to validate their efficacy and safety through preclinical and clinical studies. However, pharmacokinetic studies for active constituents or characteristic markers in botanical drugs are rare. OBJECTIVE: The objective of this review was to investigate the global state of the art in pharmacokinetic studies of active ingredients present in plant extracts and botanical drugs. A review of pharmacokinetics studies of chemical constituents of plant extracts and botanical drugs was performed, with a total of 135 studies published between January 2004 and February 2015 available in recognized scientific databases. Botanical preparations were mainly found in the form of aqueous extracts of roots and rhizomes. The most widely studied species was Salvia miltiorrhiza Bunge, and the compound most frequently used as a pharmacokinetic marker was berberine. CONCLUSION: Most studies were performed using the Sprague Dawley rat model, and the preparations were mainly administered orally in a single dose. Quantification of plasma concentrations of pharmacokinetic markers was performed mainly by liquid-liquid extraction, followed by high performance liquid chromatography coupled to mass spectrometry detector. In conclusion, in recent years there has been an increasing interest among researchers worldwide in the study of pharmacokinetics of bioactive compounds in botanical drugs and plant extracts, especially those from the Traditional Chinese Medicine.

Inhibitory effects of an extract of fruits of Physalis peruviana on some intestinal carbohydrases / Evaluación in vitro del efecto de un extracto de frutos de Physalis peruviana sobre algunas carbohidrasas intestinales

Physalis peruviana is an Andean specie whose fruits are eaten as food and also has been reported in Colombian folk medicine for diabetes mellitus treatment. In addition, previous pharmacological studies on diabetic Wistar rats, an extract of P. peruviana fruits has been showed antidiabetic activity. In order to deepen in P. peruviana action mode as antidiabetic, in this investigation were determinate the Inhibitory Concentrations 50 (IC50) of P. peruviana fruits crude extract on alpha glucosidase from S. cerevisiae and from intestinal rat powder, on maltase and alpha amylase enzymes. The kinetic behavior of the extract on each enzyme was also investigated, and the enzyme constant (Km) and maximum rate (Vmax) were determined. Extract of fruits of P. peruviana showed different IC50 for alpha glucosidase from S. cerevisiae and intestinal rat powder, suggesting greater affinity for the enzyme of mammalian source (4114.7 and 3552.7 µg/mL, respectively). For maltase, the IC50 was close to that obtained for alpha glucosidase (4191.0 µg/mL) while for alpha amylase, the extract exhibited the highest inhibition (IC50: 619.9 g/mL). Regarding kinetic behavior, the extract showed competitive inhibition on alpha-glucosidase and maltase, and on the non-competitive type of alpha amylase. These suggest that inhibition of intestinal carbohydrases is one of the modes of action for the antidiabetic activity of fruits of P. peruviana.

Physalis peruviana es una especie andina, cuyos frutos además de ser usados como alimento, son empleados en la medicina tradicional para el tratamiento de la diabetes mellitus. Además, estudios farmacológicos previos en ratas Wistar han demostrado actividad antidiabética de extractos de frutos de P. peruviana. Con el fin de profundizar en el modo de acción de la actividad antidiabética de los frutos de P. peruviana, en la presente investigación se determinó la concentración inhibitoria 50 (CI50) del extracto crudo de frutos de P. peruviana, sobre las enzimas alfa glucosidasa obtenida de S. cerevisiae y de polvo intestinal de rata, maltasa y alfa amilasa. El comportamiento cinético del extracto sobre cada una de las enzimas también fue investigado y la constante enzimática (Km) y la velocidad máxima (Vmax) fueron determinadas. El extracto de frutos de P. peruviana, mostró diferentes valores de CI50 para alfa glucosidasa obtenida de S. cerevisiae y para la obtenida de polvo intestinal de rata, sugiriendo una mayor afinidad por la enzima de origen mamífero (4114,7 and 3552,7 µg/mL, respectivamente). Para maltasa la CI50 fue cercana a la obtenida para alfa glucosidasa (4191,0 µg/mL), mientras para alfa amilasa, el extracto presentó la mayor inhibición (CI50: 619,9 g/mL). Respecto al comportamiento cinético, el extracto mostró inhibición de tipo competitiva sobre alfa glucosidasa y maltasa y no competitiva sobre alfa amilasa. Los resultados sugieren que la inhibición de carbohidrasas intestinales es uno de los modos de acción de los frutos de P. peruviana como agente antidiabético.

Isolation of C-glycosylflavonoids with α-glucosidase inhibitory activity from Passiflora bogotensis Benth by gradient high-speed counter-current chromatography.

In this study, we applied a gradient High-Speed Counter-Current Chromatography (HSCCC) method that allowed, by direct injection of an aqueous crude extract of the leaves of Passiflora bogotensis, the successful isolation of six flavonoids in a single run, with purity of each compound higher than 81%. This separation enabled the isolation of two new flavonoid glycosides, apigenin-6-C-α-l-rhamnopyranosyl-(1→2)-(6″-O-acetyl)-ß-d-glucopyranoside (2) and luteolin-6-C-α-l-rhamnopyranosyl-(1→2)-(6″-O-acetyl)-ß-d-glucopyranoside (4), and four known ones, isovitexin (1), isoorientin (3), isovitexin-2″-O-rhamnoside (5) and isoorientin-2″-O-rhamnoside (6). The structures of the isolated compounds were identified by HPLC-DAD, LC-MS, (1)H and (13)C NMR and comparison with literature data. The inhibitory activities of all of these compounds were evaluated in vitro on α-glucosidase from S. cerevisiae, and the IC50 was determinate. This is the first study concerning the chemical composition and biological activity of Passiflora bogotensis.

Biodistribution study of free and microencapsulated 6-methylcoumarin in Wistar rats by HPLC.

A sensitive, specific and reproducible HPLC method has been developed and validated for the quantitative determination of 6-methylcoumarin (6MC) in plasma and other tissues in Wistar rats. A C18 column was used with UV detection at 321 nm and a gradient system consisting of methanol-deionized water was used as mobile phase. The retention time for 6MC was 14.921 min and no interfering peaks were observed for any of the matrices. Linear relationships (r(2) > 0.997) were obtained between the peak height ratios and the corresponding biological sample concentrations over the range 0.4-12.8 µg/mL. Precision and accuracy were evaluated; the coefficient of variation and the relative error for all of the organs were <2 and 7%, respectively. The limit of quantitation was 0.20 µg/mL for the heart and 0.30 µg/mL for the other tissues evaluated. This HPLC method was successfully used in the determination of 6MC in the biodistribution study after administration of 200 mg/kg of both 6MC-free and 6MC-loaded polymeric microparticles. In this study, extensive 6MC was found, in both free and microencapsulated forms, in all the organs tested. The 6MC-free showed a range of between 1.7 and 11.5 µg/g, while the microencapsulated 6MC showed concentrations of between 6.35 and 17.7 µg/g, suggesting that 6MC improved absorption rate.

Relationship between the solution thermodynamic properties of naproxen in organic solvents and its release profiles from PLGA microspheres.

Naproxen (NPX)-loaded poly-(D,L-lactic-co-glycolic acid) (PLGA) microparticles were prepared by the emulsion-solvent evaporation method. The different organic solvents used significantly affects the properties of the microparticles obtained. These microparticles exhibited a controlled release profile that extends up to 15 days depending on the organic solvent used. The formulations did not exhibit zero- or first-order release kinetics and no agreement with Higuchi or Korsmeyer-Peppas models was obtained. In all cases, the dissolution profiles were fitted to the model proposed by Gallagher and Corrigan for PLGA systems. It was found that this model fully describes the dissolution processes. An interesting relationship between the NPX solubility in the organic solvents studied and some parameters obtained for the dissolution model of the microparticles prepared with the same solvents is thus obtained. Accordingly, it can be proposed that the drug solubility in organic solvents is relevant to estimate the physical characteristics of microparticles other than its dissolution profiles.

Efecto de algunas especies vegetales antiinflamatorias sobre la actividad enzimática de elastasa y mieloperoxidasa / Effect of some antiinflammatory plant species on elastase and myeloperoxidase enzyme activity

Se evaluó el efecto de extractos metanólicos y acuosos de las especies vegetales Critoniella acuminata, Salvia rubescens, Phenax rugosus (Poir.) Wedd y Tabebuia chrysanta G. Nicholson sobre las enzimas elastasa y mieloperoxidasa, relacionadas con el proceso de desgranulación leucocitaria, y se determinó el potencial efecto inhibitorio directo sobre la enzima o la inhibición de la desgranulación de los neutrófilos polimorfonucleares. Los extractos de Critoniella acuminata y Salvia rubescens presentaron efectos sobre el proceso de desgranulación y la actividad de las enzimas mieloperoxidasa y elastasa; en el caso de los extractos de Phenax rugosus, estos no mostraron un efecto significativo sobre ninguna de las enzimas. De la especie Tabebuia chrysanta solamente el extracto metanólico mostró efecto sobre la inhibición de la actividad elastasa.

In this work, the effect of aqueous and methanolic extracts of the plants species Critoniella acuminata, Salvia rubescens, Phenax rugosus (Poir.) Wedd and Tabebuia chrysanta G. on the enzymes elastase and myeloperoxidase, involved in degranulation leukocyte process, was evaluated, identifying the potential direct inhibitory effect on the enzyme and/or inhibition of the desgranulation of polymorphonuclear neutrophils. Extracts of Critoniella acuminata and Salvia rubescens presented effects on the degranulation process and the inhibition of the enzyme elastase and myeloperoxidase; the extracts of Phenax rugosus do not showed significant effect. Tabebuia chrysanta methanolic extract only showed effect on inhibition of elastase activity.

Thermodynamic study of the solubility of ibuprofen in acetone and dichloromethane

Thermodynamic functions, Gibbs energy, enthalpy and entropy for the solution processes of ibuprofen (IBP) in acetone and dichloromethane (DCM) were calculated from solubility values obtained at temperatures ranging from 293.15 K to 313.15 K. The respective thermodynamic functions for mixing and solvation processes as well as the activity coefficients for the solute were calculated. IBP solubility was high and proved similar in both solvents but was greater in DCM than acetone. In addition, the thermodynamic quantities for the transfer process of this drug from cyclohexane to the organic solvents were also calculated in order to estimate the contributions of hydrogen-bonds or of other dipolar interactions. The results were discussed in terms of solute-solvent interactions.

As funções termodinâmicas, energia de Gibbs, entalpia e entropia dos processos de solução de ibuprofeno (IBP) em acetona e em diclorometano (DCM) foram calculadas a partir dos valores de solubilidade, obtidos em intervalos de temperatura de 293,15 K a 313,15 K. As funções termodinâmicas respectivas para os processos de mistura e solvatação e os coeficientes de atividade para o soluto também foram calculados. A solubilidade do IBP foi grande e semelhante em ambos os solventes, mas, maior em DCM do que em acetona. Em adição, as quantidades termodinâmicas relativas ao processo de transferência desse fármaco do cicloexano para os solventes orgânicos foram, também, calculadas com o objetivo de estimar as contribuições devidas às ligações de hidrogênio ou a outras interações dipolares. Os resultados foram discutidos nos termos das interações soluto-solvente.

Efecto antinociceptivo de Critoniella acuminata, Physalis peruviana y Salvia rubescens / Antinociceptive effect of Critoniella acuminata, Physalis peruviana and Salvia rubescens

Se evaluó el efecto antinociceptivo de extractos, fracciones y compuestos de Critoniella acuminata, Physalis peruviana y Salvia rubescens mediante los métodos de placa caliente, contorsiones abdominales inducidas por ácido acético y ensayo de la formalina. La fracción de Critoniella acuminata en dosis de 100 mg/kg p.o. presentó actividad antinociceptiva al aumentar el tiempo de reacción del animal ante la aplicación de un estímulo térmico (método de la placa caliente), mientras que la fracción de Physalis peruviana, en una dosis de 100 mg/kg p. o., ejerce un efecto antinociceptivo frente al dolor generado por estímulos químicos (dolor visceral agudo) al inhibir en un 40 por ciento las contorsiones abdominales inducidas por ácido acético y el número de lamidos durante la fase ii (dolor inflamatorio agudo) en el ensayo de formalina. Estos resultados sugieren que la ayapina y la fracción de Physalis peruviana estudiadas tienen actividad antinociceptiva, con posibles mecanismos de tipo opioide y aine, respectivamente.

The antinociceptive effect of extracts, fractions and compounds of Critoniella acuminata, Physalis peruviana and Salvia rubescens were evaluated by the follow methods: Hot Plate test, acetic acid induced abdominal writhing and Formalin test. The fraction of Critoniella acuminata at doses of 100mg/kg p.o. exhibited antinociceptive effect in the hot plate test; while Physalis peruviana fraction at doses of 100 mg/kg p.o., showed an antinociceptive effect against the pain chemically induced. This fraction produced 40 percent inhibition of the acetic acid induced writhing (acute visceral nociception) and the licks during phase ii (acute inflammatory nociception)of the formalin test. The findings of this experimental study suggest that fractions of Critoniella acuminata and Physalis peruviana possess antinociceptive activity with opioid and nsaid-like mechanisms respectively.