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2.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3297-3304, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602886

RESUMO

The contents of terrestroside B and terrestrosin K in Tribuli Fructus with different degree of stir-frying were determined by high performance liquid chromatography with evaporative light-scattering detector( HPLC-ELSD). The results showed that the contents of terrestroside B and terrestrosin K were increased at first and then decreased,and both of them had the highest content at the best time of heating. The results of simulated processing of Tribulus Terrestris saponins showed that when the processing time kept constant,the contents of terrestroside B and terrestrosin K were decreased gradually with the increase of processing temperature from 180 ℃ to240 ℃. At a certain temperature,the content of terrestrosin K was increased first and then decreased with the prolongation of processing time,and reached the highest level at 5 min. However,the content of terrestroside B was increased first and then decreased with the increase of processing time only at 180 ℃,and reached the highest level at 10 min. When the processing temperature was controlled at200,220 and 240 ℃ respectively,the content of terrestroside B was decreased gradually with the increase of processing time. The simulated processing products of tribuluside A,terrestroside B and terrestrosin K were qualitatively characterized by ultra-performance liquid chromatography-time of flight mass spectrometry( UPLC-TOF/MS). It was proved that tribuluside A and terrestrosin Ⅰ containing C-22-OH were dehydroxylated in the processing of Tribuli Fructus and transformed respectively into terrestroside B and terrestrosin K containing C-20-C-22 double bond. As a result,the contents of terrestroside B and terrestrosin K were increased. The sugar chains at C-3 and C-26 positions of terrestroside B and terrestrosin K could be deglycosylated and converted into monosaccharide chain saponins and short sugar chain saponins,so the contents of terrestroside B and terrestrosin K were reduced. The study provides reference for further revealing the processing principle of Tribuli Fructus.


Assuntos
Medicamentos de Ervas Chinesas/análise , Saponinas/análise , Tribulus/química , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Frutas/química , Espectrometria de Massas em Tandem
3.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3305-3311, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602887

RESUMO

To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.


Assuntos
Curcumina/química , Metilcelulose/análogos & derivados , Química Farmacêutica , Estabilidade de Medicamentos , Metilcelulose/química , Polímeros , Solubilidade
7.
Chimia (Aarau) ; 73(7): 637-638, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31431224
8.
An Acad Bras Cienc ; 91(supp 3): e20190306, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365612

RESUMO

This manuscript describes the role of natural products in the process of drug discovery. In fact, several different natural compounds have been used as inspiration to develop new drugs. Some relevant examples are presented in chronological order.


Assuntos
Biodiversidade , Produtos Biológicos/química , Química Farmacêutica/história , Descoberta de Drogas/história , Produtos Biológicos/história , História do Século XX , Humanos
9.
AAPS PharmSciTech ; 20(7): 271, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363868

RESUMO

Dry powder inhalers have attracted more interest over the years in every aspect related to them. Interestingly, when focusing on the effects of particle morphology of the active or carrier (excipient), it is generally regarded particle size and shape to influence drug availability of aerosolized particles. However, to date, few studies have examined the effect of texture, i.e., roughness, on this relationship. The main objective of the present work is to gain a closer understanding of the influence of carrier morphology on the aerosolization performance of dry powder inhaler formulations. Image analysis and microscopy were used to visualize the aerosolization process. It is considered that the scale of morphological features on the surface of the carrier particles is responsible for the dispersion of the powder formulation, separation of the drug/carrier, and entrainment from a dry powder inhaler. Thus, for this study, the carrier particles of different surface roughness were mixed with micronized salbutamol sulphate. Aerosolization in vitro testing was used to evaluate the performance. The results indicate a connection between the qualitative surface roughness of coarse carriers and aerosolization performance during powder dispersibility. This investigation demonstrated that indeed, powder dispersion, a dynamic process, is influenced by the scale of the carrier morphology.


Assuntos
Albuterol/química , Albuterol/farmacocinética , Broncodilatadores/química , Broncodilatadores/farmacocinética , Química Farmacêutica/métodos , Inaladores de Pó Seco/métodos , Administração por Inalação , Aerossóis/química , Aerossóis/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Inaladores de Pó Seco/instrumentação , Excipientes/química , Excipientes/farmacocinética , Tamanho da Partícula , Pós , Propriedades de Superfície
10.
AAPS PharmSciTech ; 20(7): 273, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31385126

RESUMO

Orodispersible films (ODFs) are more convenient for paediatric and geriatric patients to take as compared to conventional tablets and capsules. Electrospinning has recently been attempted to produce ODFs. This study investigated the feasibility of formulating poorly water-soluble drug into ODFs using electrospinning technology coupled with the anti-solvent precipitation method. Piroxicam (PX), a poorly water-soluble drug, was chosen as a model drug. Polyvinyl alcohol and polyvinylpyrrolidone were used as film forming polymers. PX microcrystals were prepared using poloxamer as the stabilizer with the anti-solvent precipitation method, and then loaded in ODFs through the electrospinning process. The obtained ODFs were characterized using a scanning electron microscope, X-ray powder diffraction and Fourier transform infrared spectroscopy with respect to the morphology, solid state and potential molecular interaction between the model drug and polymers. The mechanical property, disintegration and dissolution rate of the obtained ODF were evaluated using dynamic mechanical analysis, a customized method and USP2 apparatus. The results showed that PX microcrystals suspended in polymeric solutions could be readily electrospun into fibrous films, where the microcrystals scattered between the fibers. The electrospun fibrous film-based ODFs exhibited satisfactory mechanical behaviour, and fast disintegration upon the polymer selection. In the dissolution tests, almost 90% of PX was dissolved within 6 min from the ODFs, whereas 40% of PX dissolved from physical mixtures in 60 min. This study demonstrated that poorly water-soluble drugs could be formulated into ODFs with satisfactory quality attributes by combining micronization and the electrospinning process.


Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Química Farmacêutica/métodos , Portadores de Fármacos/síntese química , Piroxicam/síntese química , Água/química , Administração Oral , Cristalização , Humanos , Polímeros/química , Álcool de Polivinil/química , Solubilidade , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Comprimidos , Difração de Raios X/métodos
11.
Zhongguo Zhong Yao Za Zhi ; 44(13): 2799-2805, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31359693

RESUMO

To establish and validate the design space of the Digeda-4 flavored decoction( DGD-4D) extraction process by using the quality by design( Qb D) concept. With DGD-4D decoction pieces as a model drug,with the transfer rate of aesculin,picroside I,picroside Ⅱ,geniposide and the yield of extract as critical quality attributes( CQAs),the single factor experiment design was used to determine the level of each factor; the Plackett-Burman experiment design was used to select the critical process parameters( CPPs);and the Box-Behnken experiment design was used to optimize the extraction process. The design space of the DGD-4D extraction process was established,and finally,four experimental points were selected to verify the established model. The single factor experiment determined the levels of each factor,including soaking time 60 min and 30 min,water adding volume 12 times and 8 times,extraction time 90 min and 30 min,number of extraction times 3 times and 1 time,as well as extraction temperature 100 ℃ and 90 ℃.By Plackett-Burman experimental design,the DGD-4D water addition,extraction time and number of extraction times were determined to be CPPs. The Box-Behnken experimental variance analysis showed that P of the regression model was less than 0. 01 and the misstated value was more than 0. 01,indicating that the model had good predictive ability,and the operation space of CPPs in the DGD-4D extraction process was determined as follows: the amount of water addition was 10-12 times; extraction time 50-80 min; and number of extraction times was 3 times. The design space of DGD-4D extraction process based on the concept of Qb D is conducive to improving the stability of product quality and laying a foundation for the future development of DGD-4D.


Assuntos
Química Farmacêutica/métodos , Medicamentos de Ervas Chinesas/química , Projetos de Pesquisa
12.
Nat Commun ; 10(1): 3061, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296858

RESUMO

The importance of axial chirality in enantioselective synthesis has been widely recognized for decades. The practical access to certain structures such as biaryl amino phenols known as NOBINs in enantiopure form, however, still remains a challenge. In drug delivery, the incorporation of axially chiral molecules in systematic screening has also received a great deal of interest in recent years, which calls for innovation and practical synthesis of structurally different axially chiral entities. Herein we present an operationally simple catalytic N-alkylation of sulfonamides using commercially available chiral amine catalysts to deliver two important classes of axially chiral compounds: structurally diverse NOBIN analogs as well as axially chiral N-aryl sulfonamides in excellent enantiopurity. Structurally related chiral sulfonamide has shown great potential in drug molecules but enantioselective synthesis of them has never been accomplished before. The practical catalytic procedures of our methods also bode well for their wide application in enantioselective synthesis.


Assuntos
Aminofenóis/síntese química , Sistemas de Liberação de Medicamentos , Sulfonamidas/síntese química , Alquilação , Catálise , Química Farmacêutica/métodos , Estrutura Molecular , Estereoisomerismo
13.
Nat Commun ; 10(1): 2992, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278250

RESUMO

Lysocin E, a 37-membered natural depsipeptide, induces rapid bacteriolysis in methicillin-resistant Staphylococcus aureus via a unique menaquinone-dependent mechanism, presenting a promising therapeutic lead. Despite the great medical importance, exploring the potential utility of its derivatives as new platform structures for antibiotic development has remained a significant challenge. Here, we report a high-throughput strategy that enabled the preparation of thousands of analogues of lysocin E and large-scale structure-activity relationship analyses. We integrate 26-step total synthesis of 2401 cyclic peptides, tandem mass spectrometry-sequencing, and two microscale activity assays to identify 23 candidate compounds. Re-synthesis of these candidates shows that 11 of them (A1-A11) exhibit antimicrobial activity superior or comparable to that of lysocin E, and that lysocin E and A1-A11 share L-Leu-6 and L-Ile-11. Therefore, the present strategy allows us to efficiently decipher biologically crucial residues and identify potentially useful agents for the treatment of infectious diseases.


Assuntos
Antibacterianos/farmacologia , Descoberta de Drogas/métodos , Ensaios de Triagem em Larga Escala/métodos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Química Farmacêutica/métodos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Peptídeos Cíclicos/química , Peptídeos Cíclicos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem/métodos
14.
Adv Exp Med Biol ; 1140: 299-316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347055

RESUMO

The pharmaceutical and clinical industries are imperative for the maintenance of global health and welfare and require accurate, reproducible, and high throughput analyses. Technological advancements, such as the development and implementation of liquid chromatography-tandem mass spectrometry (LC-MS), have allowed for improvements in these areas, however there is still room for development. One way in which current analyses may be improved is by the implementation of ion mobility technology. Ion mobility has the capability to produce much more comprehensive data sets, by providing separation of isomers, as well as improving throughput, with separations being performed as fast as 60 ms. Here we will discuss the potential for ion mobility to assist in the two specific areas of glycosylation monitoring of biological drugs, and vitamin D analysis, as representatives of ion mobility's potential in both the pharmaceutical and clinical industries, respectively, as well as the current hurdles of ion mobility adoption in both fields.


Assuntos
Química Farmacêutica/métodos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Glicosilação , Isomerismo , Preparações Farmacêuticas/análise , Vitamina D/análise
15.
Adv Exp Med Biol ; 1140: 685-701, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347079

RESUMO

An important and well-designed solution to overcome some of the problems associated with new drugs is provided by the molecular encapsulation of the drugs in the cyclodextrins (CDs) cavity, yielding corresponding inclusion complexes (ICs). These types of non-covalent complexes are of current interest to the pharmaceutical industry, as they improve the solubility, stability and bioavailability of the guest molecules. This review highlights several methods for cyclodextrin ICs preparation and characterization, focusing mostly on the mass spectrometry (MS) studies that have been used for the detection of noncovalent interactions of CDs inclusion complexes and binding selectivity of guest molecules with CDs. Furthermore, the MS investigations of several ICs of the CD with antifungal, antioxidants or fluorescent dyes are presented in greater details, pointing out the difficulties overcome in the analysis of this type of compounds.


Assuntos
Química Farmacêutica/métodos , Ciclodextrinas/análise , Espectrometria de Massas , Solubilidade
16.
AAPS PharmSciTech ; 20(6): 246, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286304

RESUMO

Scale-down models are indispensable and crucial tools for process understanding and continuous process improvement in product life-cycle management. In this study, a scale-down model representing commercial-scale cell culture process of adalimumab biosimilar HS016 was first developed based on constant power per volume (P/V) principle and then qualified by multivariate data analysis (MVDA) and equivalence test method. The trajectories of the bench-scale process lie in the middle of the control range of large-scale process, built by multivariate evolution model based on nutrients, metabolites, and process performance datasets. This indicates that the small-scale process performance is comparable with that of the full-scale process. The final product titer, integrated viable cell density (iVCD), viability, aggregates, acid peak content, total afucosylation level, and high mannose content recognized as key process attributes (KPAs) or critical quality attributes (CQAs) were equivalent across the scales upon comparison using equivalence test method. The qualified scale-down model was then used for process characterization using a definitive screening design (DSD) where five independent variables including pH, shifted temperature, inoculation seeding density, viable cell density (VCD) at first feeding, VCD at temperature shift were evaluated. Three quadratic polynomial models for final product titer, aggregation, and high mannose were then established using the DSD results. The design space was finally developed using a probability-based Monte Carlo simulation method and was verified with the operation setpoint and worst-case condition. The case study presented in this report shows a feasible roadmap for cell culture process characterization.


Assuntos
Desenvolvimento de Medicamentos , Adalimumab/química , Animais , Células CHO , Química Farmacêutica , Cricetinae , Cricetulus , Modelos Estatísticos , Método de Monte Carlo , Análise Multivariada , Temperatura Ambiente
17.
AAPS PharmSciTech ; 20(7): 269, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350661

RESUMO

Process analytical technologies are implemented within the pharmaceutical manufacturing process to rectify issues associated with current sampling methods. These include inline monitoring methods such as passive vibration measurements which are non-intrusive and less costly to other methods. In the final mixing stage of the tablet manufacturing process, a lubricant is added to ensure the mixture is ejected from the tablet die cleanly. To monitor this process, an accelerometer was attached to the lid of the V-blender loaded with various particles and magnesium stearate. At a fixed fill level, the lubricant concentration and particle mass were varied to investigate the effects of changes in process parameters on the signal vibrations measured by the sensor, the coefficient of restitution, and the flowability. It was found that measured vibrations from stress waves propagated upon collisions of the particles with the V-shell respond to and can distinguish differences in particles. As well, the magnesium stearate layer around particles alters energy dissipation and subsequently the measured vibrations. A mixing endpoint of uniform distribution of magnesium stearate with primary particles can be identified from vibrations measured by an accelerometer attached to the lid of the V-blender. The flowability change was considered negligible in the particles due to their physical morphology. These findings indicate that passive vibration measurements can be a viable, non-intrusive monitoring method while providing insight into V-blender mixing behaviors as well as improving process efficiency.


Assuntos
Química Farmacêutica , Vibração , Excipientes , Lubrificantes , Ácidos Esteáricos/química , Comprimidos
20.
Artigo em Alemão | MEDLINE | ID: mdl-31161229

RESUMO

Preparations of hemp, Cannabis sativa, have been used for thousands of years as recreational and therapeutic drugs. The most important constituents are the psychoactive (-)-trans-∆9-tetrahydrocannabinol (THC), a partial agonist at cannabinoid (CB) receptors CB1 and CB2, and the non-psychoactive pleiotropic cannabidiol (CBD). Both compounds are highly lipophilic, like the endogenous CB receptor agonists, the arachidonic acid derivatives anandamide and arachidonoyl glycerol. The CB receptors belong to the family of G protein-coupled receptors, and the first X­ray crystal structures of both CB receptors subtypes have recently been obtained, which will facilitate the rational design of novel synthetic ligands. Besides the already largely established indications such as chronic pain, chemotherapy-induced vomiting, multiple sclerosis-associated spasms, and cachexia, there is preliminary evidence for several further cannabinoid effects, which will have to be confirmed by clinical studies.


Assuntos
Canabinoides , Cannabis , Química Farmacêutica , Canabidiol , Dronabinol , Alemanha
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