Propolis Standardized Extract (EPP-AF®), an Innovative Chemically and Biologically Reproducible Pharmaceutical Compound for Treating Wounds

The aim of this study was to develop a formulation, containing the propolis standardized extract (EPP-AF®), which can assist in the healing of skin lesions. To achieve this objective the antimicrobial activity and chemical composition of the propolis extract was determined. The final product was subjected to in vitro and in vivo pre-clinical evaluation. The broth macrodilution method was used to determine the antimicrobial activity of the extracts and formulations against the microorganisms most commonly found in burns, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis. Wistar rats with puncture wounded skin were used to evaluate the wound healing properties of propolis. The results of chemical and biological characterization demonstrated the batch-to-batch reproducibility of the standardized extract which is an unprecedented result. The antimicrobial and wound healing activity of the pharmaceutical studied showed the best results when samples contain 3.6% propolis, suggesting that this is the most promising composition

Acupuncture, Yoga, Homeopathy, and Apitherapy under the Vibrational Point of View

Albert Einstein was one of the greatest physicists in recent history and his contributions changed the paradigm of science in the 20th century. From this, it was proposed the understanding that all matter is energy, and we can assume the understanding that the human body is a dynamic energy system. Energy and matter are two different manifestations of the same universal substance from which we are all formed, atoms. It is known that the movement between the constituent parts of the atom (electrons, neutrons, protons and smaller particles) and the forces that connect them, generates energy. Since the atoms are in constant movement, what can be measured is vibration. Therefore, in this chapter, we propose to present some millenary therapies like acupuncture, yoga, apitherapy and, more recently, Homeopathy, under the point of view of vibrational integrative therapies, exploring the hypothesis that through these therapies we can adapt the waves generated in the bodies to transform them into personalized therapeutic agents

The Lyophilization Process Maintains the Chemical and Biological Characteristics of Royal Jelly

The alternative use of natural products, like royal jelly (RJ), may be an important tool for the treatment of infections caused by antibiotic-resistant bacteria. RJ presents a large number of bioactive substances, including antimicrobial compounds. In this study, we carried out the chemical characterization of fresh and lyophilized RJ and investigated their antibacterial effects with the purpose of evaluating if the lyophilization process maintains the chemical and antibacterial properties of RJ. Furthermore, we evaluated the antibacterial efficacy of the main fatty acid found in RJ, the 10-hydroxy-2-decenoic acid (10H2DA). Chromatographic profile of the RJ samples showed similar fingerprints and the presence of 10H2DA in both samples. Furthermore, fresh and lyophilized RJ were effective against all bacteria evaluated; that is, the lyophilization process maintains the antibacterial activity of RJ and the chemical field of 10H2DA. The fatty acid 10H2DA exhibited a good antibacterial activity against Streptococcus pneumoniae. Therefore, it may be used as an alternative and complementary treatment for infections caused by antibiotic-resistant S. pneumoniae

Strong Electronic Identification: Survey & Scenario Planning

The deployment of more high-risk services such as online banking and government services on the Internet has meant that the need and demand for strong electronic identity is bigger today more than ever. Different stakeholders have different reasons for moving their services to the Internet, including cost savings, being closer to the customer or citizen, increasing volume and value of services among others. This means that traditional online identification schemes based on self-asserted identities are no longer sufficient to cope with the required level of assurance demanded by these services. Therefore, strong electronic identification methods that utilize identifiers rooted in real world identities must be provided to be used by customers and citizens alike on the Internet. This thesis focuses on studying state-of-the-art methods for providing reliable and mass market strong electronic identity in the world today. It looks at concrete real-world examples that enable real world identities to be transferred and used in the virtual world of the Internet. The thesis identifies crucial factors that determine what constitutes a strong electronic identity solution and through these factors evaluates and compares the example solutions surveyed in the thesis. As the Internet become more pervasive in our lives; mobile devices are becoming the primary devices for communication and accessing Internet services. This has thus, raised the question of what sort of strong electronic identity solutions could be implemented and how such solutions could adapt to the future. To help to understand the possible alternate futures, a scenario planning and analysis method was used to develop a series of scenarios from underlying key economic, political, technological and social trends and uncertainties. The resulting three future scenarios indicate how the future of strong electronic identity will shape up with the aim of helping stakeholders contemplate the future and develop policies and strategies to better position themselves for the future

Development and characterization of high-absorption microencapsulated organic propolis EPP-AF® extract (i-CAPs)

The demand for organic and functional food continues to increase yearly. Among the available functional foods, propolis is a bee product that has various beneficial properties, including antimicrobial, antioxidant, and anti-inflammatory activities. However, it generally is only available in ethanol solution, which has poor bioavailability, as it is relatively insoluble in water. The use of such ethanol extracts is often objectionable because of the alcohol content and because they have a strong and striking taste. Development of alternatives that can efficiently and safely increase solubility in water, and that meet organic production specifications, has been a challenge. To address these concerns, microcapsules were developed using spray-dryer technology from an emulsion based on EPP-AF® propolis and gum arabic (i-CAPS). These propolis-loaded microcapsules were characterized using FT-IR, SEM, TGA, HPLC, and spectrophotometric techniques, along with determination of antimicrobial, antioxidant, antitumor, anti-inflammatory, and antihypercholesterolemic activities, as well as permeability in in vitro models. The production system resulted in microcapsules with a spherical shape and an encapsulation efficiency of 93.7 0.7%. They had IC50s of 2.654 0.062 and 7.342 0.058 g/mL by FRAP and DPPH antioxidant methods, respectively. The EPP-AF® i-CAPS also had superior antimicrobial activity against Gram-positive bacteria. Antitumor activity was calculated based on the concentration that inhibited 50% of growth of AGS, Caco-2, and MCF-7 cell strains, giving results of 154.0 1.0, 117 1.0, and 271.0 25 g/mL, respectively. The microcapsule presentation reduced the permeation of cholesterol by 53.7%, demonstrating antihypercholesterolemic activity, and it improved the permeability of p-coumaric acid and artepillin C. The IC50 for NO production in RAW264.7 cells was 59.0 0.1 g/mL. These findings demonstrate the potential of this new propolis product as a food and pharmaceutical ingredient, though additional studies are recommended to validate the safety of proposed dosages.CNPq financially supported this research through the CNPQ/MCTI/SEMPI No. 021/2021 process on RHAE modality, contract number 424727/2021-8. It was also supported by São Paulo Research Foundation (FAPESP) grant #2017/04138-8, CNPq (grant 309614/2021-0; INCT-INFO), CNPq grants 350088/2022-5 and 350089/2022-1, São Paulo Research Foundation (FAPESP) (grant no. 2013/07276-1). The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support by national funds FCT/MCTES to CIMO (UIDB/00690/2020 and UIDP/00690/2020) and SusTEC (LA/P/0007/2021). Thanks to the project GreenHealth, Norte-01- 0145-FEDER-000042.info:eu-repo/semantics/publishedVersio

Brazilian Green Propolis: Anti-Inflammatory Property by an Immunomodulatory Activity

The immunomodulatory and anti-inflammatory activities of green propolis extracts from Apis mellifera were investigated using acute and chronic inflammation models. Swiss mice were anesthetized and a cotton pellet granuloma was implanted in subcutaneous tissue. Then the mice were divided into six groups and received apyrogenic water or different propolis extracts by oral route (5 mg/kg). According to the treatment the groups were designated as E1A, E1B, E10, E11, and E12. The control group received apyrogenic water. The treatment was performed by six days when the mice were killed. The blood and the bronchoalveolar lavage (BAL) were collected to measure the leukocyte recruitment. In acute pulmonary inflammation, Balb/c mice received lipopolysaccharide (LPS) of Escherichia coli by intranasal route for three days. Concomitantly the mice received by oral route apyrogenic water (control) or E10 and E11 propolis extracts. BAL was performed to assess the inflammatory infiltrate and cytokine quantification. The results showed that the E11 extract has anti-inflammatory property in both models by the inhibition of proinflammatory cytokines and increase of anti-inflammatory cytokines suggesting an immunomodulatory activity

Development and evaluation of a sustained release pharmaceutical form containing standardized propolis extract for the treatment of burns

Nos últimos anos houve um crescente interesse no desenvolvimento de formas farmacêuticas de liberação sustentada e liberação controlada para uso oral, tópico e parenteral. Tensoativos não-iônicos são vastamente empregados como solubilizantes, emulsificantes, estabilizantes, umectantes e como sistemas de liberação em cosméticos e medicamentos. O copolímero não-iônico em bloco composto por polioxietilenopolioxipropileno foi empregado neste trabalho por apresentar rearranjo micelar em solução aquosa e produzir mudança na viscosidade em função da alteração da temperatura, sendo que este pode ser aquecido e esfriado sem prejuízo das suas propriedades. Tal forma farmacêutica termorreversível foi desenvolvida e avaliada. Pacientes queimados são particularmente susceptíveis à colonização bacteriana e infecção em função da ruptura física da pele normal e redução da imunidade celular. Assim, a fim de se obter uma proteção do sistema fisiológico exposto, alguns autores recomendam o uso de uma \"pele artificial\" nos pacientes queimados, protegendo desta forma frente aos agressores do meio externo. Atualmente, observamos um crescente interesse em produtos naturais de aplicação tópica. Muitos tipos de inflamações de pele, queimaduras e ferimentos estão sendo tratados com extrato de própolis. A própolis, uma resina coletada pelas abelhas de muitas fontes vegetais, teve as seguintes propriedades biológicas comprovadas: antioxidante, antiinflamatória, antibiótica, antifúngica, anticancer, dentre outras. O desenvolvimento de um sistema de liberação de fármacos para uso tópico se justifica nas queimaduras, uma vez que a aplicação e reaplicação de produtos constituem um processo doloroso. Neste trabalho foi desenvolvido e caracterizado este tipo de forma farmacêutica contendo própolis. Demonstrou-se que a substância marcadora da própolis neste trabalho, DPB (2,2- dimetil-6-carboxietenil-8-prenil-2H-l-benzopirano), se mostrou estável nas preparações estudadas (± 10%), sendo que as propriedades de termorreversibilidade dos géis foram mantidas. A caracterização reológica das amostras mostrou que elas apresentam comportamento viscoelastico com temperatura de geleificação para o Gel 02 e Gel 03 de, respectivamente, 10°C e 6°C. Os controles e o Gel 01 não apresentaram temperatura de geleificação nas condições estudadas. Os estudos de liberação in vitro demonstraram que as amostras apresentam cinética de ordem zero. Os resultados encontrados possibilitam os estudos de fase pré-clínica e dependendo dos resultados, também a fase clínicaIn recent years there has been increasing interest in the development of prolonged-action and controlled release drug delivery systems for oral, topical, and parenteral use. Nonionic surfactants are widely used in cosmetics and pharmaceuticals as solubilizers, emulsifiers, stabilizers, wetting agents and as delivery systems. One non-ionic polyoxyethylene-polyoxypropylene block copolymer was ysed in this work because its micellar rearrangement in aqueous solution will produce a change in viscosity with change in temperature and it can be cooled and warmed many times without changing its properties. This pharmaceutical preparation was developed and studied. Burn patients, are particularly susceptible to bacterial colonization and infection due to the physical disruption of the normal skin barrier and the reduction in cell-mediated immunity. In order to solve the exposition of physiologic system, some authors recommend an \"artificial skin\" to protect the burn patients organism of externai invasors. Actually, we observed an increasing interest in natural products for topical aplication. Many kinds of some skin inflammatory diseases such as: burns and wounds, are being treated with propolis extract. Propolis is a resinous hive product collected by honeybees from various plant sources and also it has been reported to possess various biological activities, such as antioxidant, antiinflammatory, antibiotic, antifungal and anticancer. The development of a drug delivery systems to topical use is justified in several burns, since the aplication and reaplication of product is a dolorous process. In our work we developed and characterized these kind of pharamceutical form. We demonstrated that the substance DPB (2,2- dimetil-6-carboxietenil-8-prenil-2H-l-benzopirano), was stable in the studied preparations (± 10%) and the thermoreversible properties were maintained. The rheologycal characterization of samples showed that they are viscoelastic fluids with temperature of gelation to GEL 02 and GEL 03, respectively, 10°C and 6°C. The Controls and GEL 01 did not show temperature of gelation in the studied conditions. In vitro drug release experiments demonstrated that samples maintain a zero-order delivery. The found results encourage the undertaking of new experiments with the formulations in pre-dinical phase and depending on the obtained results, the clinicai phase could also be undertake

Pre-clinical and clinical research of a thermoreversible gel formulation containing standardized propolis extract (EPP-AF) to reduce healing time of lesions in burn victims.

O estudo realizado compreendeu a avaliação pré-clínica e clínica de uma forma farmacêutica de liberação sustentada contendo extrato padronizado de própolis EPP-AF para o tratamento de queimaduras. Utilizamos um polímero com características termorreversíveis que possibilitaram a obtenção de um produto que se mantém na forma líquida quando a baixas temperaturas e geleifica in situ. A forma farmacêutica proposta visa maior comodidade e adesão do paciente, obtenção de um tecido epitelial organizado e menor tempo para a cicatrização da área. Neste trabalho, foi avaliada a atividade antimicrobiana in vitro, do extrato de própolis e dos géis obtidos, através da técnica de difusão em agar e também através do método de microdiluição em microplacas contendo caldo de enriquecimento e o revelador trifeniltetrazólio, frente aos microrganismos S. aureus, M. luteus e P. aeruginosa. O potencial mutagênico foi estudado em modelo experimental utilizando micronúcleos de sangue periférico de ratos wistar. A histologia do tecido formado em lesão induzida com a utilização de um punch para biópsia e a eficácia do produto em pacientes queimados também foram objeto deste estudo. As áreas doadoras foram utilizadas como modelos experimentais. Os resultados demonstraram que o extrato de própolis apresentou atividade frente aos microrganismos pesquisados sendo que os géis não se difundiram em disco. Em microdiluição, o modelo utilizado para estudo da atividade antimicrobiana não foi adequado ao microrganismo M. luteus, mas foi possível a obtenção do CIM para S. aureus e P. aeruginosa, que foram respectivamente, 50 ug/mL e 200 ug/mL. O produto não apresentou potencial genotóxico nos tratamentos agudo, sub-agudo e crônico. A pesquisa clínica demonstrou que o gel termorreversível contendo extrato padronizado de própolis 3,6%p/v apresentou tempo de cicatrização semelhante à pomada contendo nitrofurazona (furacin®), tratamento referência utilizado na Unidade de Queimados do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo.The present paper examines the pre-clinical and clinical evaluation of a pharmaceutical form that provides sustained delivery of a formulation containing standardized propolis extract EPP AF to the treatment of burn wounds. There has been used a polymer with thermoreversible characteristics which made possible the obtaintion of a product that maintains its liquid state in low temperatures and provides in situ gelling property. The proposed pharmaceutical form intends to enhance patients comfort and acceptance, to obtain a histological well-organized skin tissue and to reduce wound healing time. This study evaluated in vitro the antimicrobial activity of propolis extract and obtained gels using the agar-diffusion method and also a broth microdilution method with microdillution in microplates containing serially diluted antimicrobial and triphenilthetrazolium agent, against microorganisms S. aureus, M. luteus e P. aeruginosa, the mutagenic potential using micronuclei of peripheral blood Wistar rats experimental models, the histology of neo-formed tissue induced by lesions done with a punch and the effectiveness of the products in burn patients, using skin-grafting donnor sites like experimental models. The results show that propolis extract has activity against the listed microorganisms and that the gels did not spread into agar medium plate. In the microdilution method, the used model for the antimicrobial activity study is not adequate to the microorganism M. luteus, but it was possible for the obtention of CIM to S. aureus e P. aeruginosa, which were, respectively, 50 ug/mL e 200 ug/mL. The product did not show genotoxic potential to acute, subacute and chronic treatments. The clinical research show that the thermoreversible gel formulation containing standardized propolis extract 3,6%p/v presented wound healing time similar to the reference treatment used in the Burn Victims Unity witch is nitrofurazone cream (furacin®)

Pre-clinical and clinical research of a thermoreversible gel formulation containing standardized propolis extract (EPP-AF) to reduce healing time of lesions in burn victims.

O estudo realizado compreendeu a avaliação pré-clínica e clínica de uma forma farmacêutica de liberação sustentada contendo extrato padronizado de própolis EPP-AF para o tratamento de queimaduras. Utilizamos um polímero com características termorreversíveis que possibilitaram a obtenção de um produto que se mantém na forma líquida quando a baixas temperaturas e geleifica in situ. A forma farmacêutica proposta visa maior comodidade e adesão do paciente, obtenção de um tecido epitelial organizado e menor tempo para a cicatrização da área. Neste trabalho, foi avaliada a atividade antimicrobiana in vitro, do extrato de própolis e dos géis obtidos, através da técnica de difusão em agar e também através do método de microdiluição em microplacas contendo caldo de enriquecimento e o revelador trifeniltetrazólio, frente aos microrganismos S. aureus, M. luteus e P. aeruginosa. O potencial mutagênico foi estudado em modelo experimental utilizando micronúcleos de sangue periférico de ratos wistar. A histologia do tecido formado em lesão induzida com a utilização de um punch para biópsia e a eficácia do produto em pacientes queimados também foram objeto deste estudo. As áreas doadoras foram utilizadas como modelos experimentais. Os resultados demonstraram que o extrato de própolis apresentou atividade frente aos microrganismos pesquisados sendo que os géis não se difundiram em disco. Em microdiluição, o modelo utilizado para estudo da atividade antimicrobiana não foi adequado ao microrganismo M. luteus, mas foi possível a obtenção do CIM para S. aureus e P. aeruginosa, que foram respectivamente, 50 ug/mL e 200 ug/mL. O produto não apresentou potencial genotóxico nos tratamentos agudo, sub-agudo e crônico. A pesquisa clínica demonstrou que o gel termorreversível contendo extrato padronizado de própolis 3,6%p/v apresentou tempo de cicatrização semelhante à pomada contendo nitrofurazona (furacin®), tratamento referência utilizado na Unidade de Queimados do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo.The present paper examines the pre-clinical and clinical evaluation of a pharmaceutical form that provides sustained delivery of a formulation containing standardized propolis extract EPP AF to the treatment of burn wounds. There has been used a polymer with thermoreversible characteristics which made possible the obtaintion of a product that maintains its liquid state in low temperatures and provides in situ gelling property. The proposed pharmaceutical form intends to enhance patients comfort and acceptance, to obtain a histological well-organized skin tissue and to reduce wound healing time. This study evaluated in vitro the antimicrobial activity of propolis extract and obtained gels using the agar-diffusion method and also a broth microdilution method with microdillution in microplates containing serially diluted antimicrobial and triphenilthetrazolium agent, against microorganisms S. aureus, M. luteus e P. aeruginosa, the mutagenic potential using micronuclei of peripheral blood Wistar rats experimental models, the histology of neo-formed tissue induced by lesions done with a punch and the effectiveness of the products in burn patients, using skin-grafting donnor sites like experimental models. The results show that propolis extract has activity against the listed microorganisms and that the gels did not spread into agar medium plate. In the microdilution method, the used model for the antimicrobial activity study is not adequate to the microorganism M. luteus, but it was possible for the obtention of CIM to S. aureus e P. aeruginosa, which were, respectively, 50 ug/mL e 200 ug/mL. The product did not show genotoxic potential to acute, subacute and chronic treatments. The clinical research show that the thermoreversible gel formulation containing standardized propolis extract 3,6%p/v presented wound healing time similar to the reference treatment used in the Burn Victims Unity witch is nitrofurazone cream (furacin®)