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1.
BMC Complement Altern Med ; 19(1): 348, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796063

RESUMO

BACKGROUND: Ficus palmata (Fig), are distributed in different parts of the world, and are used in traditional medicine to treat various ailments including inflammation, tumor, epilepsy, jaundice, influenza and bacillary dysentery. The present study aimed to evaluate the antidiarrheal, antisecretary, antispasmodic, antiulcer and anti motility properties of Ficus palmata. METHODS: In-vivo, in-vitro and in-silico techniques were used to investigate various gastrointestinal effects of Ficus palmata. Antidiarrheal, antisecretary, antispasmodic, antiulcer, anti motility and molecular docking were performed using castor oil induced diarrhea and fluid accumulation, isolated tissue preparations, ethanol-HCl induced ulcer assay, charcoal meal transit time and Auto Doc Vina. RESULTS: Ficus palmata crude extract (Fp.Cr) exhibited protection against castor oil-induced diarrhea in mice and dose-dependently inhibited intestinal fluid secretions. Fp.Cr caused relaxation of spontaneous and K+ (80 Mm)-induced contractions in isolated rabbit jejunum preparations. It showed protective effect against gastric ulcers induced by ethanol-hydrochloric acid in rats. Fp.Cr reduced distance travelled by charcoal meal in the gastrointestinal transit model in mice. The plant constituents: psoralenoside and bergapten showed high binding affinities (E-value ≥ - 6.5 Kcal/mol) against histaminergic H1, calmodulin and voltage gated L-type calcium channels, while showed moderate affinities (E-value ≥7 Kcal/mol) against dopaminergic D2, adrenergic α1, muscranic M3, mu-opioid, whereas revealed lower affinities (E-value ≥9.5 Kcal/mol) vs. muscranic M1, histaminergic H2 and H+/K+ ATPase pump. Germanicol acetate and psoralene exhibited weak affinities against aforementioned targets. CONCLUSION: This study reveals that Ficus palmata possesses anti-diarrheal, anti-secretory, anti-spasmodic, anti-motility and anti-ulcer activities. The various constituents reveal different binding affinities against target proteins, which mediate the gastrointestinal functions.


Assuntos
Diarreia , Ficus , Fármacos Gastrointestinais , Parassimpatolíticos , Extratos Vegetais , Animais , Óleo de Rícino/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/metabolismo , Feminino , Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/metabolismo , Fármacos Gastrointestinais/farmacologia , Trânsito Gastrointestinal/efeitos dos fármacos , Jejuno/química , Jejuno/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Simulação de Acoplamento Molecular , Parassimpatolíticos/química , Parassimpatolíticos/metabolismo , Parassimpatolíticos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Coelhos , Ratos Sprague-Dawley , Receptores de Superfície Celular/química , Receptores de Superfície Celular/metabolismo
2.
Carbohydr Polym ; 225: 115204, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521305

RESUMO

Enzyme digestion of starch granules encapsulated within cell walls in pulse depends on both the intactness of cellular structure as well as the retention of the ordered structure of starch during processing. However, the role of cell wall permeability in starch digestion, as affected by processing conditions, has not been fully elucidated. In this study, Kubali bean cells were isolated under different processing conditions (i.e., high pressure-heating, hydrothermal processing, and acid-alkali treatments) individually and in combinations to elucidate the structure and in vitro digestion of entrapped starches in the cells. The morphological features and crystalline structure of entrapped starches suggest that intact cell walls hinder the starch gelatinization, which in turn lowers the enzyme susceptivity. Alteration of cell wall permeability induced by different processing conditions is further evaluated through the diffusion of fluorescence-tagged dextran probes. Among all the treatments, cells isolated with the pressure-cooking method exhibited higher cell wall permeability. The study suggests that the in vitro starch digestion of plant foods can be optimized through the selection of processing method that has the least impact on cell wall permeability.


Assuntos
Parede Celular/química , Cicer/metabolismo , Amido/química , Culinária/métodos , Digestão , Fármacos Gastrointestinais/química , Estrutura Molecular , Pancreatina/química , Permeabilidade
3.
Carbohydr Polym ; 218: 343-354, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31221339

RESUMO

Taxifolin possesses gastroprotective property but is characterized by low water solubility, is instabile in alkaline medium, and is degraded by the intestinal bacteria flora. The purpose of the work was therefore to produce a gastroadhesive formulation to prolong taxifolin residence time and release in the stomach. We first demonstrated that taxifolin is stable in simulated gastric fluid with or without pepsin and mucus, and is able to cross pig gastric mucus layer and stomach mucosa. Next, gastromucoadhesive microparticles composed of Syloid® AL-1 mesoporous silica, chitosan and HPMC were produced using spray-drying. Microparticles were characterized by a spherical shape and a mean volume-equivalent diameter around 12 µm. The optimized microparticles were able to release taxifolin and to adhere to pig stomach mucosa for 5 h.


Assuntos
Quitosana/química , Portadores de Fármacos/química , Fármacos Gastrointestinais/química , Quercetina/análogos & derivados , Adesividade , Animais , Liberação Controlada de Fármacos , Excipientes/química , Mucosa Gástrica/metabolismo , Microtecnologia , Mimusops/química , Tamanho da Partícula , Permeabilidade , Quercetina/química , Sementes/química , Dióxido de Silício/química , Suínos
4.
Food Chem Toxicol ; 131: 110579, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202940

RESUMO

Disintegration of the intestine caused by deoxynivalenol (DON), which is a fungal metabolite found in cereal grain-based human and animal diets, triggers severe intestinal inflammatory disease. Hydrolyzed wheat gluten (HWG) can promote the development of intestine. Therefore, HWG was administered orally to male mice on 1-14 days, and DON was administered to them on 4-11 days. Feed, water intake and body weight were recorded all over the experimental period. Blood samples were collected then the mice were sacrificed to collect the jejunum for crypt isolation and culture. The intestinal morphology was observed by electron microscopy, and Western blotting was used to investigate intestinal stem cell (ISC) proliferation and differentiation, as well as the primary regulatory mechanism of the Wnt/ß-catenin signaling. The results showed that HWG increased the average daily gain and average daily water intake of mice under DON-induced injury conditions, and increased the jejunum weight, villous height in the jejunum, and promoted jejunal crypt cell expansion. The DON-induced decrease in Wnt/ß-catenin activity, the expression of Ki67, PCNA and KRT20 were rescued by HWG in the jejunum, crypt and enteroid, as well as the number of goblet cells and Paneth cells. Furthermore, HWG increased jejunum diamine oxidase (DAO) activity. In conclusion, HWG alleviates DON-induced intestinal injury by enhancing ISC proliferation and differentiation in a Wnt/ß-catenin-dependent manner.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glutens/uso terapêutico , Enteropatias/prevenção & controle , Células-Tronco/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/uso terapêutico , Glutens/química , Hidrólise , Enteropatias/induzido quimicamente , Jejuno/citologia , Jejuno/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Tricotecenos , Triticum/química , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
5.
Swiss Med Wkly ; 149: w20071, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30994926

RESUMO

Arsenic is a toxicant that has no dose threshold below which exposures are not harmful. Here I report a curious association of chronic homeopathic arsenic ingestion with nonspecific symptoms in a Swiss teenager. For about 4 years she had taken globules of a freely purchasable homeopathic remedy containing inorganic arsenic (iAs), infinitesimally diluted to D6 (average arsenic content per single globule: 0.85 ± 0.08 ng). In the previous 7 months she had taken 20 to 50 globules daily (average 30 ng arsenic daily). She complained of nausea, stomach and abdominal cramps, diarrhoea and flatulence, headache, dizziness, anxiety, difficulty concentrating, insomnia, snoring, leg cramps and fatigue, loss of appetite, increased thirst and sweating, reduced diuresis, weight gain, paleness and coolness of both hands with a furry feeling of the hands, eczema of the hands, arms and legs, conjunctivitis and irregular menstruation. The physical and laboratory examinations showed a body mass index of 30 kg/m2, acne vulgaris, bilateral spotted leukonychia, eczema of hands, arms and legs, non-pitting oedema of the legs, elevated plasma alkaline phosphatase activity, folate deficiency and severe vitamin D3 insufficiency. The arsenic concentration in her blood was <0.013 µmol/l, and arsenic was undetectable in her scalp hair. The total iAs concentration was 116 nmol/l in the morning urine and 47 nmol/l in the afternoon urine. The urinary arsenic concentration decreased and the patient’s complaints improved upon interruption of the arsenic globules, vitamin D3, thiamine and folic acid supplementation, and symptomatic therapy. It is concluded that an avoidable toxicant such as inorganic arsenic, for which no scientific safe dose threshold exists, should be avoided and not be found in over-the-counter medications.


Assuntos
Intoxicação por Arsênico/etiologia , Arsenicais/efeitos adversos , Fármacos Gastrointestinais/efeitos adversos , Homeopatia/efeitos adversos , Adolescente , Feminino , Fármacos Gastrointestinais/química , Humanos
6.
Carbohydr Polym ; 215: 151-159, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30981340

RESUMO

We report hybrid gels based on a high-amylose starch and microcrystalline cellulose with demonstrated properties for gastric-floating drug delivery purposes. The starch/cellulose gels were prepared by ionic liquid dissolution and regeneration, resulting in a continuous surface and a porous interior and a type-II crystalline structure of cellulose. These polysaccharide gels displayed satisfactory elasticity (0.88), recovery (0.26-0.36) and equilibrium swelling (1013-1369%). The hybrid gels were loaded with ranitidine hydrochloride as a model drug and subsequently, low-density starch/cellulose tablets were fabricated by vacuum-freeze-drying. In vitro tests in a simulated gastric fluid indicate that the 3:7 (wt./wt.) starch/cellulose system could maintain the buoyancy for up to 24 h with a release of 45.87% for the first 1 h and a sustained release for up to 10 h. Therefore, our results have demonstrated the excellent gastric-floating ability and sustainable drug release behavior of the starch/cellulose hybrid gels.


Assuntos
Celulose/química , Portadores de Fármacos/química , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/química , Amido/química , Preparações de Ação Retardada , Excipientes/química , Géis/química , Comprimidos
7.
J Enzyme Inhib Med Chem ; 34(1): 789-798, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30871382

RESUMO

In this study, we investigated whether jervine (J) could prevent gastrointestinal (GI) side effects of abdominopelvic radiotherapy (RT) in Wistar-Albino female rats. Rats were divided into five groups: control (C), J only (J), J administered at 5 mg/kg/days for 7 days, RT only (RT), J before RT (J + RT), J administered for seven days before RT, J both before and after RT (J + RT + J), and J administered for 7 days before RT and after RT for 3 days. The weights of rats were measured on the 1st, 7th, and 10th days of the study. Rats were sacrificed to obtain tissues from the liver and intestine, which was followed by taking blood samples intracardially. In addition, the tissues were stained with pyruvate dehydrogenase (PDH) immunohistochemically. In our study, J supplementation markedly reduced weight loss, and histopathological, immunohistochemical, biochemical results suggest that J had a protective effect on GI toxicity following RT.


Assuntos
Fármacos Gastrointestinais/uso terapêutico , Lesões por Radiação/patologia , Lesões por Radiação/prevenção & controle , Alcaloides de Veratrum/uso terapêutico , Animais , Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/farmacologia , Ratos , Ratos Wistar , Alcaloides de Veratrum/química , Alcaloides de Veratrum/farmacologia
8.
Scand J Gastroenterol ; 54(1): 18-26, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30678499

RESUMO

There have been major advancements in the treatment of inflammatory bowel disease (IBD) over the past three decades. However despite significant progress, the best available treatments continue to demonstrate variable efficacy in patients and are associated with adverse effects. Therefore there remains an unmet clinical need for ongoing therapeutic advances for IBD. In recent years nanomedicines have emerged as promising diagnostic and therapeutic tools. Nanoparticles in particular show promise to facilitate targeted oral drug delivery in IBD. Here we discuss the pitfalls of current therapies and explore the potential for nanoparticles to improve the treatment of IBD. This review examines the range of conventional and novel therapies which have benefited from nanoparticle-mediated delivery and highlights the proven therapeutic efficacy of this approach in preclinical models. These strategies under development represent a novel and innovative treatment for IBD.


Assuntos
Sistemas de Liberação de Medicamentos , Fármacos Gastrointestinais/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Nanomedicina/tendências , Administração Oral , Animais , Modelos Animais de Doenças , Fármacos Gastrointestinais/química , Humanos , Nanopartículas
9.
Eur J Pharmacol ; 848: 105-111, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30689999

RESUMO

Nimesulide is a relatively selective cyclooxygenase (COX)-2 inhibitor, non-steroidal anti-inflammatory drug; it has been discovered in 1971 and firstly commercialized in Italy in 1985. There is much evidence that the pharmacological profile of nimesulide is peculiar and not shared with the other COX-2 selective inhibitors, suggesting that other molecular mechanisms besides inhibition of COX-2 derived prostaglandins are involved. Similarly, experimental data suggest that the gastrointestinal safety of nimesulide cannot be ascribed only to a COX-1 sparing effect. On the inflammatory process, the efficacy of nimesulide is dependent upon a wide spectrum of actions, due to the combination of effects on immune and non-immune cells. Early data demonstrated a central role for cyclic AMP (cAMP) in the anti-inflammatory effect of nimesulide; more recently, we have shown the involvement of the pathway ecto-5'-nucleotidase/adenosine A2A receptor. To date, the molecular mechanism(s) that confers uniqueness to nimesulide have not yet been defined. To go inside the mechanism of action of an existing drug, such as nimesulide, would be helpful to refine its therapeutic use but also to identify new targets for novel therapeutic anti-inflammatory approach. Here, we focus on accumulated evidence for a peculiar pharmacological profile of nimesulide.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Sulfonamidas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/química , Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/farmacologia , Humanos , Neutrófilos/efeitos dos fármacos , Neutrófilos/enzimologia , Sulfonamidas/química
10.
J Pharm Pharmacol ; 71(4): 643-673, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30062750

RESUMO

OBJECTIVES: Drugs used to treat gastrointestinal diseases (GI drugs) are widely used either as prescription or over-the-counter (OTC) medications and belong to both the 10 most prescribed and 10 most sold OTC medications worldwide. The objective of this review article is to discuss the most frequent interactions between GI and other drugs, including identification of the mechanisms behind these interactions, where possible. KEY FINDINGS: Current clinical practice shows that in many cases, these drugs are administered concomitantly with other drug products. Due to their metabolic properties and mechanisms of action, the drugs used to treat gastrointestinal diseases can change the pharmacokinetics of some coadministered drugs. In certain cases, these interactions can lead to failure of treatment or to the occurrence of serious adverse events. The mechanism of interaction depends highly on drug properties and differs among therapeutic categories. Understanding these interactions is essential to providing recommendations for optimal drug therapy. SUMMARY: Interactions with GI drugs are numerous and can be highly significant clinically in some cases. While alterations in bioavailability due to changes in solubility, dissolution rate, GI transit and metabolic interactions can be (for the most part) easily identified, interactions that are mediated through other mechanisms, such as permeability or microbiota, are less well-understood. Future work should focus on characterising these aspects.


Assuntos
Interações Medicamentosas , Fármacos Gastrointestinais/administração & dosagem , Gastroenteropatias/tratamento farmacológico , Animais , Disponibilidade Biológica , Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/farmacocinética , Humanos , Medicamentos sem Prescrição/administração & dosagem , Medicamentos sem Prescrição/química , Medicamentos sem Prescrição/farmacocinética , Medicamentos sob Prescrição/administração & dosagem , Medicamentos sob Prescrição/química , Medicamentos sob Prescrição/farmacocinética , Solubilidade
11.
ScientificWorldJournal ; 2018: 7463584, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30327583

RESUMO

The bark, leaves, and roots of Albizia adianthifolia are highly sought after in tropical Africa as herbal medicines. Therefore, the aim of this study was to review the botany, medicinal uses, phytochemistry, and pharmacological properties of A. adianthifolia so as to provide baseline data required for evaluating the therapeutic potential of the species. Information on the botanical profile, medicinal uses, phytochemistry, and pharmacological properties of A. adianthifolia was undertaken using databases such as ScienceDirect, SciFinder, Pubmed, Google Scholar, Medline, SCOPUS, EThOS, ProQuest, OATD, and Open-thesis. Preelectronic literature search of conference papers, scientific articles, books, book chapters, dissertations, and theses was carried out at the University library. Literature search revealed that A. adianthifolia is used as purgative and herbal medicine for diabetes, eye problems, gastrointestinal problems, haemorrhoids, headache, neurodegenerative disorders, reproductive problems in women, respiratory problems, wounds and pain, skin diseases, sexually transmitted infections, and ethnoveterinary medicine. Phytochemical compounds identified from the species include apocarotenoids, chalcone, dipeptide, elliptosides, essential oils, fatty acids, flavonoids, histamine, imidazolyl carboxylic acid, prosapogenins, steroids, triterpene saponins, and triterpenoids. Pharmacological studies revealed that A. adianthifolia extracts and compounds have acetylcholinesterase enzyme inhibitory, anthelmintic, antiamoebic, antibacterial, antimycobacterial, anti-sexually transmitted infections, antifungal, anti-inflammatory, antioxidant, anxiolytic, and antidepressant, cognitive-enhancing, haemolytic, hypoglycemic and antihyperglycemic, immunomodulatory, and cytotoxicity activities. Detailed studies on the pharmacokinetics, in vivo, and clinical research involving compounds isolated from A. adianthifolia and extracts of the species are required.


Assuntos
Albizzia , Etnobotânica/métodos , Compostos Fitoquímicos/uso terapêutico , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Plantas Medicinais , África/etnologia , Analgésicos/química , Analgésicos/isolamento & purificação , Analgésicos/uso terapêutico , Animais , Etnobotânica/tendências , Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/isolamento & purificação , Fármacos Gastrointestinais/uso terapêutico , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/uso terapêutico , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Fitoterapia/tendências , Casca de Planta , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Raízes de Plantas
12.
Eur J Pharm Biopharm ; 133: 214-223, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30342089

RESUMO

One of the major disadvantages associated with macromolecules therapy is that most of them can only be administered parenterally. Exenatide, an efficient anti-diabetic drug, incretin mimetic, is currently administered subcutaneously (SC) causing compliance issues. Nanoparticles (NPs) are considered a promising solution for oral delivery of this drug. In order to overcome exenatide's inability to cross the enterocytes and to increase its stability in the gastrointestinal (GI) tract, we encapsulated exenatide into a nano-in-micro delivery system. This drug delivery system (DDS) improved the relative oral bioavailability of exenatide, in comparison to Byetta® injection SC. In this study, we report about the efficacy of this DDS to improve glycemic parameters in diabetic ob/ob mice. Our results suggested that our DDS successfully lowered blood glucose levels (BGL) raised insulin levels, decreased glycated hemoglobin and maintained the body weight of the mice. These findings validate the efficacy of this DDS in promoting oral delivery of exenatide and will hopefully improve patient compliance and adherence. The potential of this DDS to encapsulate other leading peptides and proteins, such as insulin, was also evaluated in this study. It was found that peptides up to 6 kDa can be efficiently encapsulated, but the in-vivo performance is also dependent on other physicochemical properties.


Assuntos
Exenatida/administração & dosagem , Exenatida/química , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/química , Trato Gastrointestinal/metabolismo , Nanopartículas/química , Administração Oral , Animais , Disponibilidade Biológica , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Injeções Subcutâneas/métodos , Insulina/metabolismo , Masculino , Camundongos , Proteínas/administração & dosagem , Proteínas/química
13.
J Med Chem ; 61(17): 7589-7613, 2018 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-30141927

RESUMO

Bile acid signaling and metabolism in the gastrointestinal tract have wide-ranging influences on systemic disease. G protein-coupled bile acid receptor 1 (GPBAR1, TGR5) is one of the major effectors in bile acid sensing, with demonstrated influence on metabolic, inflammatory, and proliferative processes. The pharmacologic utility of TGR5 agonists has been limited by systemic target-related effects such as excessive gallbladder filling and blockade of gallbladder emptying. Gut-restricted TGR5 agonists, however, have the potential to avoid these side effects and consequently be developed into drugs with acceptable safety profiles. We describe the discovery and optimization of a series of gut-restricted TGR5 agonists that elicit a potent response in mice, with minimal gallbladder-related effects. The series includes 12 (TGR5 EC50: human, 143 nM; mouse, 1.2 nM), a compound with minimal systemic availability that may have therapeutic value to patients with type 2 diabetes mellitus, nonalcoholic steatohepatitis, or inflammatory bowel disease.


Assuntos
Vesícula Biliar/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Receptores Acoplados a Proteínas-G/agonistas , Tiazolidinas/química , Animais , Cães , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/química , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Células HEK293 , Humanos , Células Madin Darby de Rim Canino , Masculino , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas-G/metabolismo , Relação Estrutura-Atividade
14.
Artigo em Inglês | MEDLINE | ID: mdl-29886290

RESUMO

MP3950 is being developed as a gastroprokinetic candidate compound. To illustrate the pharmacokinetic profiles, absolute bioavailability after intravenous administration and oral administration with MP3950 as well as tissue distribution in vivo, an UPLC-MS/MS approach which was rapid and selective was developed to determine MP3950 in plasma and tissue of rat. Sample pre-treatment of plasma sample was one-step protein precipitation. 0.1% formic acid containing 5 mmol/L ammonium acetate-methanol(55/45,v/v) was used for isocratic elution on a Waters ACQUITY UPLC® BEH C18 (50 mm × 2.1 mm, 1.7 µm) to achieve the separation. The analysis was performed in MRM mode via positive ESI mode. LLOQ of the method was 10 ng/mL, and the linearity up to 10,000 ng/mL. The intra-day precision (relative standard deviation, RSD) was 4.0-9.0% and the inter-day precision was 4.2-10.6%. The accuracy (relative error, RE) was -1.2-2.4%. Tissue samples were collected from the brain, heart, liver, spleen, lung, kidney, stomach, duodenum, small intestine, large intestine, appendix and skeletal muscle. The same liquid chromatographic and mass spectrometric conditions were used, and it's proven that this method was feasible to analyze the MP3950 in tissues with good precision and accuracy over the range from 10 to 5000 ng·mL-1. It was found that the concentration of MP3950 is higher in digestive system. The tissue distribution, pharmacokinetic and bioavailability of MP3950 in rats were carried out by the method for the first time, which can provide enough information for the further development and investigation of MP3950.


Assuntos
Benzamidas/análise , Benzamidas/farmacocinética , Animais , Benzamidas/química , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Fármacos Gastrointestinais/análise , Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/farmacocinética , Modelos Lineares , Masculino , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodos , Distribuição Tecidual
15.
Trends Biotechnol ; 36(10): 987-992, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29861288

RESUMO

Structural and functional differences between REMICADE and its two FDA-approved biosimilars appear to have clinical implications. We suggest a personalized biosimilar substitution approach based on prescribed indication, biosimilar afucosylation level, and a patient's FCGR3A polymorphism. We also advocate for establishing glycosylation variation limits for biosimilar approvals.


Assuntos
Antirreumáticos/administração & dosagem , Medicamentos Biossimilares/administração & dosagem , Fármacos Gastrointestinais/administração & dosagem , Infliximab/administração & dosagem , Medicina de Precisão/métodos , Antirreumáticos/química , Medicamentos Biossimilares/química , Fármacos Gastrointestinais/química , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/química , Polimorfismo Genético , Receptores de IgG/genética , Febre Reumática/tratamento farmacológico
16.
Int J Pharm ; 545(1-2): 19-26, 2018 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-29702241

RESUMO

The present study aimed to clarify the applicability of a self-micellizing solid dispersion of tranilast (SMSD/TL) to the treatment of inflammatory bowel diseases (IBD) using an experimental colitis model. SMSD/TL with several loading amounts ranging from 10 to 50% was prepared using a wet-milling system. The physicochemical properties of SMSD/TL were evaluated in terms of the dissolution behavior, morphology, and particle size distribution. Animal studies were conducted to evaluate oral bioavailability in rats and anti-inflammatory effects in a rat model of chemically induced colitis. SMSD/TL with drug loading of 15% (SMSD/TL15) showed enhanced dissolution behavior at pH 1.2, compared with other tested other formulations. After the dispersion of SMSD/TL15 in deionized water, fine micelles formed with an average diameter of 137 nm. SMSD/TL15 (10 mg-TL/kg) exhibited about 147- and 34-fold greater value for Cmax and the area under the curve of plasma concentration vs. time than crystalline TL, respectively. Although the anti-inflammatory effect on the colitis model was very limited in the crystalline TL (2 mg/kg) group, inflammatory events, such as myeloperoxidase activity and thickening of the submucosa in colon tissues, were significantly suppressed in the SMSD/TL15 (2 mg-TL/kg) group. Based on these findings, SMSD/TL might be a more efficacious dosage option for improved IBD treatment.


Assuntos
Anti-Infecciosos/administração & dosagem , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Portadores de Fármacos , Fármacos Gastrointestinais/administração & dosagem , Mucosa Intestinal/efeitos dos fármacos , ortoaminobenzoatos/administração & dosagem , Administração Oral , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Disponibilidade Biológica , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/patologia , Modelos Animais de Doenças , Composição de Medicamentos , Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/farmacocinética , Concentração de Íons de Hidrogênio , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Micelas , Infiltração de Neutrófilos/efeitos dos fármacos , Tamanho da Partícula , Peroxidase/metabolismo , Ratos Sprague-Dawley , Solubilidade , Tecnologia Farmacêutica/métodos , Ácido Trinitrobenzenossulfônico , ortoaminobenzoatos/química , ortoaminobenzoatos/farmacocinética
17.
Acta Pharm ; 68(2): 159-170, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29702482

RESUMO

The purpose of this study was to prepare a mosapride citrate-resin (Amberlite® IRP 88) complex and orally fast-disintegrating tablets of the resin complex. The resinate complex of mosapride-Amberlite® IRP 88, mass ratio 2:1, was prepared in an ethanol-water solution. The effects of alcohol concentration, temperature, and pH of the solution on complex formation were evaluated. The complex physicochemical properties were characterized by differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. Orally disintegrating tablets were prepared by direct compression and were optimized using the response surface method. Optimized orally fast-disintegrating tablets disintegrated within 18 s. The pH dependence of mosapride release from the tablet decreased drug dissolution in simulated saliva, whereas it promptly released in the pH 1.0 solution. The data reported herein clearly demonstrate that tablets containing the mosapride-Amberlite® IRP 88 complex for oral disintegration could be particularly useful for patients with swallowing difficulties.


Assuntos
Benzamidas/administração & dosagem , Etanol/química , Fármacos Gastrointestinais/administração & dosagem , Morfolinas/administração & dosagem , Resinas Sintéticas/química , Administração Oral , Benzamidas/química , Varredura Diferencial de Calorimetria , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Fármacos Gastrointestinais/química , Humanos , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Morfolinas/química , Saliva/metabolismo , Solubilidade , Comprimidos , Difração de Raios X
18.
Food Funct ; 9(4): 2080-2089, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29594273

RESUMO

The effect of the addition of galactooligosaccharides (GOS) on sterol bioaccessibility in three plant sterol (PS)-enriched milk-based fruit beverages (without GOS addition (MfB) and with 2.5 g (MfB-G2) and 5.0 g (MfB-G5) GOS per 250 mL) was evaluated after micellar gastrointestinal digestion. Cholesterol bioaccessibility was very similar among beverages, though a slight significant increase (from 80% to 85%) was observed by the addition of 5.0 g GOS. The addition of GOS did not affect total PS bioaccessibility (≈37%). Based on the results obtained after micellar digestion, it has been demonstrated that these beverages could be a suitable food matrix for simultaneous enrichment with PS and GOS. The harmonized in vitro digestion model INFOGEST was applied to the MfB beverage, but the cholesterol content could not be quantified due to its contribution of bile salts. Hence, it was proposed: (i) a change in porcine bile salt concentration from 10 mM to 1.4 mM (in order to compare with micellar digestion); or (ii) a change of bile salt origin (bovine instead of porcine), maintaining physiological concentration (10 mM, INFOGEST condition). Both options allowed cholesterol quantification, with bioaccessibilities of 62% (reduction of bile salts) and 38% (replacement of the bile salt source), whereas plant sterol bioaccessibilities were 22% and 14%, respectively. Therefore, the change of bile salt origin maintaining INFOGEST concentration is proposed as a method to evaluate sterol (cholesterol and PS) bioaccessibility in these beverages, demonstrating the need for the selection of appropriate conditions of the INFOGEST harmonized method according to the food matrix and compounds to be determined.


Assuntos
Laticínios , Digestão , Aditivos Alimentares/química , Sucos de Frutas e Vegetais , Modelos Biológicos , Fitosteróis/metabolismo , Trissacarídeos/química , Animais , Ácidos e Sais Biliares/química , Ácidos e Sais Biliares/metabolismo , Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/prevenção & controle , Colesterol na Dieta/análise , Colesterol na Dieta/metabolismo , Laticínios/análise , Aditivos Alimentares/administração & dosagem , Tecnologia de Alimentos/métodos , Tecnologia de Alimentos/normas , Alimentos Especializados/análise , Sucos de Frutas e Vegetais/análise , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/química , Glicolipídeos/metabolismo , Glicoproteínas/metabolismo , Guias como Assunto , Humanos , Técnicas In Vitro/normas , Doenças Inflamatórias Intestinais/dietoterapia , Doenças Inflamatórias Intestinais/prevenção & controle , Micelas , Valor Nutritivo , Projetos de Pesquisa/normas , Trissacarídeos/administração & dosagem
19.
Drug Dev Ind Pharm ; 44(7): 1171-1184, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29429379

RESUMO

INTRODUCTION: In this study, different nifedipine-loaded formulations were prepared to treat pylorospasm, a sphincter muscle disorder characterized by delayed gastric emptying process. The efficacy of formulation was evaluated in patients by subjective assessment, gamma scintigraphic approaches, and confocal microscopy. METHODS: Nifedipine-loaded different formulations such as sucrose bead, pellets, and microparticles (slugging method, ionotropic gelation, and chemical denaturation) were designed. The studies were performed on 50 subjects, of which 30 subjects were treated with optimized nifedipine loaded microcapsules while 20 subjects were given capsule becosule-Z as a control. The efficacy of formulation was assessed by comparing symptoms like dyspepsia, abdominal pain, abdominal fullness, poor appetite, nausea, vomiting, and irregular motion. The effectiveness of formulation was also assessed by gamma scintigraphic studies by determining the rate of emptying of a radioactivity labeled standard meal from patients' stomach into the duodenum. Confocal microscopy was used to assess targeting potential of developed formulation. RESULTS: Drug-loaded alginate-chitosan microcapsules were found to be satisfactory, in terms of controlled drug release, surface morphology, and bioadhesive properties and thus selected for in vivo studies. Clinical studies revealed the efficacy of formulation in abolishing various GI symptoms at high altitude. Associated symptoms such as dyspepsia, abdominal pain, poor appetite, nausea, vomiting, and irregular motion were recovered by 75, 62, 76.5, 86.7, 85.7, and 37.5%, respectively in nifedipine-treated patients. In comparison, 73.7, 40, 33.3, 40, 20, and 0% recoveries were observed in patients given control treatment only. Gamma Scintigraphic studies in lab also revealed 2.425 ± 0.245 (p < .05) times improvement in gastric emptying rate in patients with diabetic gastroparesis. Confocal analysis showed better targeting and penetration in pyloric region when formulation was administered in form of high-density microcapsules. CONCLUSIONS: Results strongly suggest that nifedipine loaded mucoadhesive formulation has a targeting potential which accelerates gastric emptying process in gastroparesis patients, and thus the formulation might prove useful as a potent prokinetic agent.


Assuntos
Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/uso terapêutico , Gastroparesia/tratamento farmacológico , Nifedipino/química , Nifedipino/uso terapêutico , Adulto , Idoso , Alginatos/química , Animais , Química Farmacêutica/métodos , Quitosana/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/uso terapêutico , Método Duplo-Cego , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculares/tratamento farmacológico , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos
20.
Arch Physiol Biochem ; 124(5): 390-396, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29303617

RESUMO

Medicinal plants have always had an important place in the therapeutic arsenal of humanity and particularly in the treatment of gastrointestinal tract diseases. Myrtus communis L., known as common myrtle, is native to Southern Europe, North Africa, and Western Asia. The different parts of this plant are used as antiinflammatory, antiulcer, antidiabetic, urinary antiseptic, and to treat the respiratory and digestive systems diseases. For the first time, an exhaustive bibliographic research of the seeds of myrtle berries has been carried out. As a result, it has been found that this plant is very rich in biologically active compounds such as phospholipids, polyunsaturated fatty acids, and phenolic compounds. This has made it effective in the treatment of digestive diseases. In order to emphasize the importance of myrtle berries seeds, this review has been established by discussing its botanical, morphological, phytochemical, ethnomedicinal studies as well as its effect on digestive tract diseases.


Assuntos
Suplementos Nutricionais , Fármacos Gastrointestinais/uso terapêutico , Gastroenteropatias/terapia , Myrtus/química , Extratos Vegetais/uso terapêutico , Sementes/química , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/uso terapêutico , Antiulcerosos/efeitos adversos , Antiulcerosos/química , Antiulcerosos/isolamento & purificação , Antiulcerosos/uso terapêutico , Antidiarreicos/efeitos adversos , Antidiarreicos/química , Antidiarreicos/isolamento & purificação , Antidiarreicos/uso terapêutico , Suplementos Nutricionais/efeitos adversos , Descoberta de Drogas , Etnobotânica/métodos , Etnofarmacologia/métodos , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/isolamento & purificação , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/imunologia , Gastroenteropatias/fisiopatologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/fisiopatologia , Humanos , Myrtus/crescimento & desenvolvimento , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Sementes/crescimento & desenvolvimento
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