Unipharma S.A. : creating value delivering pharmaceutical drugs

It was early January 2008 when the company finally started operating. The result of several months of planning, after-work hours and sleepless nights all came down to that phone call. On the other side, speaking, was the sales director of one of the most important hospitals in Portugal. Pedro Azevedo could not be more pleased. Unipharma, S.A. is a Portuguese company that operates in the wholesaling business of the pharmaceutical industry. Due to its innovative business plan focused on the unlicensed, off-label and orphan drugs, the company has been consistently growing year after year, being the internationalization process a not so far away reality. The aim of this case study is to describe the creation process of the company from the moment where the opportunity was identified until the present day. It also includes an overview of the industry, as well as all the relevant data regarding the company’s creation and operation, so that the business itself is better understood

Polysaccharides from the infusions of P. tridentatum, F. angustifoliaand M. suaveolens

The use of plant infusions for medicinal purposes is present in secular traditions of all civilizations. In Portugal, in Trás-os-Montes region, the small shrub (Pterospartum tridentatum), the narrow-leafed ash (Fraxinus angustifolia), and the apple mint (Mentha suaveolens) are plants used for such purposes. According to the popular tradition, the infusions of P. Tridentatum, F. Angustifolia, and M. suaveolens protect against diabetes, high blood pressure, high levels of cholesterol, and uric acid [1].These health benefits are associated with the presence of phenolic compounds, essential oils, and polysaccharides, among others. Although phenolic compounds and essential oils have been studied in detail for more than two decades, the structures of the polysaccharides present in plant infusions and their involvement in the health benefits is still incipient. Infusions were prepared in two different ways: a traditional method, consisting in the infusion of the vegetal material with boiling water during five minutes (Method A), and a more intensive method, consisting in the infusion of the vegetal material with boiling water during four hours (Method B). The high molecular weight material was obtained by concentrating and dialyzing the extracts obtained by Methods A and B. The high molecular weight material obtained with the Method B contained more glycosidic material than the obtained with Method A. The high molecular weight material was fractionated using ethanol precipitation yielding fractions especially rich in uronic acids besides considerable amounts of arabinose, galactose, glucose and rhamnose, suggesting the presence of pectic polysaccharides. Detailed monomeric composition and glycosidic linkages of each fraction will be presented

Monomeric composition and linkage analysis of the polysaccharides present in the infusions of Fraxinus angustifolia leaves

In the Trás-os-Montes region, the use of infusions of Fraxinus angustifolia dried leaves as a protection against high levels of cholesterol, blood pressure and uric acid is widespread. Pectic polysaccharides isolated from the infusions of some medicinal plants have been reported as biologically active [1,2]. Pectic poly-saccharides have been described as structurally complex polymers, exhibiting different polymeric building blocks: homogalacturonans (HG), rhamnogalacturonans-I (RG-I), rhamnogalacturonans-II (RG-II) and xylogalacturonans (XG) [3]. The backbone of RG-I can be partly substituted with various side chains, such as arabinans, type-I and type-II arabinogalactans (AG-I and AG-II). The aim of this work is to provide a first insight of the nature of the pectic polysaccharides present in the infusions of F. angustifolia dried leaves

Composição glicosídica e actividade antioxidante de extractos de infusões de folhas de freixo (Fraxinus angustifolia)

Neste trabalho foram preparadas infusões de folhas de freixo secas. Cada infusão foi dividida em duas fracções, tendo uma sido utilizada para a obtenção do material polimérico por diálise (Dial) e a outra submetida a uma extracção em fase sólida C18, sendo a fase aquosa recolhida composta pelo material não retido (C18 H2O) e a fracção de metanol composta pelo material retido e eluído neste solvente (C18 MeOH). A análise da composição glicosídica mostrou que a fracção C18 H2O era rica em glucose e manose; a fracção C18 MeOH era rica em glucose e a fracção Dial era rica em ácidos urónicos, arabinose, galactose e glucose. A fracção C18 H2O era a mais pobre em compostos fenólicos e a que apresentou menor actividade antirradicalar. As fracções C18 MeOH e Dial apresentaram actividades antirradicalares semelhantes entre si, apesar de possuírem quantidades de compostos fenólicos totais distintas. A fracção Dial, constituída por material de peso molecular superior a 12-14 kDa, foi ainda sujeita a uma análise de ligações glicosídicas, através da análise por GC-MS dos respectivos acetatos de alditol parcialmente metilados. O resultado obtido permitiu inferir a presença de resíduos glicosídicos característicos de arabinogalactanas do tipo II, xiloglucanas e xilanas

Isolation and characterization of polysaccharides from Fraxinus angustifolia infusions

In folk medicine there is a great variety of plants that are used for as infusions, such as Camellia sinensis and Matricaria recutita. Despite the reported biological activities and health benefits of these infusions, most of the knowledge achieved so far is based on folk tradition passed over several generations, without a sound scientific basis. In Trás-os-Montes region, the dried leaves of the narrow-leafed ash “freixo” (Fraxinus angustifolia) are used for medicinal purposes, particularly against high levels of cholesterol, blood pressure and uric acid. These health benefits are associated with the presence of biologically active compounds such as phenolic compounds, essential oils, and polysaccharides, among others. Although phenolic compounds and essential oils have been studied in detail for more than two decades, the structures of the polysaccharides present in plant infusions and their involvement in the health benefits is still incipient. Therefore, in this work we present a study regarding the structure of the polysaccharides present in the infusions of “freixo” dried leaves. “Freixo” leaves were collected and dried according to the popular tradition and used for the preparation of the infusions. The polysaccharides were recovered by dialysis, fractionated by ethanol precipitation and anion exchange chromatography, yielding fractions with distinct ethanol solubility and uronic acid content. Sugar and linkage analysis evidenced the presence of pectic polysaccharides, frequently reported as immunostimulatory active. The assessment of the biological activity of these fractions is in progress

Polysaccharides from the infusions of P. tridentatum, F. angustifolia, and M. suaveolens

The use of plant infusions for medicinal purposes is present in secular traditions of all civilizations. In Portugal, in Trás-os-Montes region, the small shrub (Pterospartum tridentatum), the narrow-leafed ash (Fraxinus angustifolia), and the apple mint (Mentha suaveolens) are plants used for such purposes. According to the popular tradition, the infusions of P. Tridentatum, F. Angustifolia, and M. suaveolens protect against diabetes, high blood pressure, high levels of cholesterol, and uric acid [1].These health benefits are associated with the presence of phenolic compounds, essential oils, and polysaccharides, among others. Although phenolic compounds and essential oils have been studied in detail for more than two decades, the structures of the polysaccharides present in plant infusions and their involvement in the health benefits is still incipient. Infusions were prepared in two different ways: a traditional method, consisting in the infusion of the vegetal material with boiling water during five minutes (Method A), and a more intensive method, consisting in the infusion of the vegetal material with boiling water during four hours (Method B). The high molecular weight material was obtained by concentrating and dialyzing the extracts obtained by Methods A and B. The high molecular weight material obtained with the Method B contained more glycosidic material than the obtained with Method A. The high molecular weight material was fractionated using ethanol precipitation yielding fractions especially rich in uronic acids besides considerable amounts of arabinose, galactose, glucose and rhamnose, suggesting the presence of pectic polysaccharides. Detailed monomeric composition and glycosidic linkages of each fraction will be presented

Polysaccharide composition of Fraxinus angustifolia Leave infusions

The use of plant infusions with medicinal purposes, such as the ones from members of the Fraxinus genus, is an ancient practice that has been reported by popular medicine [1]. The health benefits are associated with the presence of phenolic compounds and polysaccharides, among others [2]. Although phenolic compounds have been studied in detail for more than two decades, the characterization of the polysaccharides present in plant infusions and their involvement in the health benefits is still incipient. The polysaccharides of F. angustifolia dried leaves were recovered by dialysis (12-14 kDa cut-off). The high molecular weight material comprised approximately 2% of the total soluble material obtained from the infusions. Total sugars in fraction were 27%, with a monomeric composition rich in Ara (15.2 ± 1.9 %), Gal (17.7 ± 0.4 %), Glc (30.1 ± 1.3 %) and uronic acids (18.9 ± 2.9 %). Analysis of the glycosidic linkage composition showed the presence of (1→6)-, (1→3,6)- and (1→3)-Gal with a proportion of 5:3:1, respectively, and also a high percentage of Ara terminally linked, diagnostic of the presence of Type II arabinogalactans [3]. Similar features have been reported in biological active Type II pectic arabinogalactans obtained from aqueous extracts of the roots of C. tinctorium [4]. The EC50 for the antioxidant activity (DPPH radical assay) was 0.34±0.04 mg/mL, showing lower antioxidant activity than that reported for aqueous extracts of hazel leaves (0.16-0.20 mg/mL) [5], but higher than that reported for the table olives ‘‘alcaparras’’ aqueous extracts (0.47± 0.03) [6]. The high molecular weight material was fractionated by ethanol precipitation in four distinct fractions: WI, a cold water insoluble residue (20.3% yield); Et50, material precipitated with 50% ethanol (17.9%); Et75, material precipitated with 75% ethanol (21.1%); and SN, material that remained soluble in 75% ethanol solution (40.7%). Fractions Et50, Et75 and SN were submitted to solid phase extraction (C18 cartridge). The Et50 and Et75 C18 non-retained fractions were rich in Ara (13.5-17.2%), Gal (27.1-35.7%) and uronic acids (25.9-35.2%), suggesting the occurrence of heterogeneous pectic arabinogalactans. NMR experiments are in progress in order to evaluate the detailed structure of the type II pectic arabinogalactans isolated from the infusions of dried leaves of F. angustifolia

Compostos de Maillard e perfil de aminoácidos da Pêra Passa de Viseu.

A pêra de S. Bartolomeu (Pyrus communis L.) é um produto tradicional secado ao ar livre, de cor castanho-avermelhada e com propriedades elásticas únicas. Para desenvolver uma metodologia capaz de substituir a secagem solar tradicional sem que as suas propriedades organolépticas sejam alteradas, estão em fase de desenvolvimento metodologias alternativas como a utilização de estufas solares ou um túnel de ar quente. É possível que os compostos castanhos formados por reacções entre aminoácidos e açúcares (reacções de Maillard) possam contribuir para a cor deste produto. Para avaliar esta hipótese, foram analisados os perfis de aminoácidos livres e de aminoácidos constituintes das proteínas em peras frescas e em peras provenientes de diferentes metodologias de secagem em duas colheitas, assim como foi quantificada a ocorrência de furosina, carboximetil-lisina (CML) e carboxietil-lisina (CEL), compostos diagnóstico da ocorrência de reacções de Maillard. A secagem tradicional causou uma diminuição para cerca de metade do conteúdo de aminoácidos livres. A Pro foi o aminoácido livre detectado em maior quantidade nas peras secadas, contrastando com a quantidade elevada de Asx detectada nas peras frescas. Em relação aos aminoácidos das proteínas, não foram observadas modificações com a secagem. Todos os tipos de peras secadas apresentaram furosina, CML e CEL. Os níveis mais elevados foram detectados para as peras secadas tradicionalmente, enquanto as peras secadas no túnel de ar quente, que não possuíam cor castanho-avermelhada, apresentaram os valores inferiores. Os valores detectados são semelhantes aos descritos para alimentos processados termicamente de forma moderada, como o leite UHT e carnes e peixes cozinhados. A secagem da pêra de S. Bartolomeu promove a ocorrência de reacções de Maillard características de produtos processados termicamente que podem contribuir para a coloração característica do produto

The antioxidant activity of polysaccharides: a structure-function relationship overview

Over the last years, polysaccharides have been linked to antioxidant effects using both in vitro chemical and biological models. The reported structures, claimed to act as antioxidants, comprise chitosan, pectic polysaccharides, glucans, mannoproteins, alginates, fucoidans, and many others of all type of biological sources. The structural features linked to the antioxidant action include the polysaccharide charge, molecular weight, and the occurrence of non-carbohydrate substituents. The establishment of structure/function relationships can be, however, biased by secondary phenomena that tailor polysaccharides behavior in antioxidant systems. In this sense, this review confronts some basic concepts of polysaccharides chemistry with the current claim of carbohydrates as antioxidants. It critically discusses how the fine structure and properties of polysaccharides can define polysaccharides as antioxidants. Polysaccharides antioxidant action is highly dependent on their solubility, sugar ring structure, molecular weight, occurrence of positive or negatively charged groups, protein moieties and covalently linked phenolic compounds. However, the occurrence of phenolic compounds and protein as contaminants leads to misleading results in methodologies often used for screening and characterization purposes, as well as in vivo models. Despite falling in the concept of antioxidants, the role of polysaccharides must be well defined according with the matrices where they are involved.publishe

Caracterização dos polissacarídeos das paredes celulares da grainha de uva com vista à valorização do óleo por aplicação de enzimas exógenas

ISBN 972-9372-29-