ESTEVE

Monistrol de Montserrat, Spain
Monistrol de Montserrat, Spain

Time filter

Source Type

Patent
Esteve | Date: 2017-03-08

A dry powder inhaler for a capsule containing dry powder, the inhaler comprising a base body having a capsule receptacle, two actuator buttons arranged on opposing sides of the base body and two perforation needles, each needle being fixedly connected to an actuator button and movable relative to the base body towards each other from a normal position to a perforation position along an actuation direction to perforate a capsule arranged in the capsule receptacle, wherein the capsule receptacle is arranged in an inclined angle within the range of about 40 to about 50 with respect to the actuation direction.


Patent
Esteve | Date: 2017-03-08

A dry powder inhaler for a capsule containing dry powder, the inhaler comprising a housing having a capsule receptacle, two actuator buttons arranged on opposing sides of the housing and two perforation needles, each needle being fixedly connected to an actuator button and movable relative to the housing towards each other from a normal position to a perforation position along an actuation direction to perforate a capsule arranged in the capsule receptacle, wherein a first end of each actuator button is connected to the housing at a lower portion of the housing and in that a second free end of each actuator button is movable into the perforation position such that the perforation needle is moved along a circular line.


ESTEVE, a leading chemical-pharmaceutical group, invests heavily in the research & development of new formulations, and commercializes medicine and innovative formulations in order to achieve a high level of excellence in the healthcare market.


The new research project NGN-PET was launched in the framework of the Innovative Medicine Initiative (IMI), the largest public-private partnership (PPP) for health research worldwide co-funded by the EU and the European pharmaceutical industry. The NGN-PET consortium unites the expertise and knowledge of industry partners from the European Federation of Pharmaceutical Industries and Associations (EFPIA), small and medium-sized enterprises (SMEs) and academia. Together they will investigate neuron-glia interactions aiming to develop authentic cellular (co-culture) assays to discover improved treatments of neuropathic pain using neuronal and glial cell types derived from human induced pluripotent stem cells (iPSC), and their co-cultures. The primary objective is to provide a translational platform for the identification, validation and testing of neuropathic pain targets in preclinical and human-relevant test systems suitable for drug discovery. Chronic pain is a serious debilitating disease which greatly reduces the quality of life for the individual patients. In Europe, 20% of the population are affected which causes considerable socioeconomic burden of over 200 bn € per year[1]. Chronic pain of neuropathic origin has a population prevalence of 8.2%[2]. Neuropathic pain arises after insults such as surgery, trauma, diabetes, chemotherapy or viral infections, and its prevalence is expected to rise in the future due to the ageing society. Current treatments for chronic pain have limited efficacy, leaving about 60% of patients without adequate pain relief[1]. Moreover, these therapies address only symptoms not the causes of the pain, and are therefore not curative. In fact, the aetiologies of the disease are poorly understood which hinders the development of new analgesics with improved efficacies. One of the major findings of the last decade in pain research is that non-neuronal cells play a very active role in the development of sensory abnormalities. In particular, glia - like Schwann cells, microglia, or astrocytes - contribute directly to modulation of neuronal functions. The NGN-PET consortium aims to explore neuron-glial interactions in subtypes of neuropathic pain which are induced by chemotherapy or trauma, and to develop human-predictive test systems that can be implemented in the drug discovery process. These cellular systems will use preclinical tissues and human iPSC-derived neuron-glia co-cultures in novel high-throughput screening platforms. We hope this new science helps in identifying novel more efficacious treatments for neuropathic pain patients. To achieve these ambitious goals, a consortium of 6 partners, with the support of IMI, has been formed. NGN-PET brings together experts from industry, SMEs and academia in a synergistic public-private partnership. NGN-PET is supported by over 3million euros from IMI2 and industry partners in direct and in-kind contributions. The project duration is 3 years. The consortium will disseminate the results through publication in high-impact scientific journals, applying open access policy whenever possible, or in scientific meetings by means of poster or oral presentations. Online outreach of the project publications will be performed via the project website. The NGN-PET project is coordinated by Axxam; the project leader is ESTEVE, supported by Grünenthal as project Co-Leader. Axxam is an innovative Partner Research Organization (iPRO) based in Milan, Italy. Axxam is a leading provider of integrated discovery services across Life Sciences industries including: pharmaceuticals, crop protection, animal health, cosmetics, fragrances, food and beverages. The company has consolidated expertise across a broad range of discovery disciplines and innovative technologies including: assay development, high-throughput screening of both the Axxam high quality compound collections (synthetic and natural) or those provided by our clients, compound management, hit identification and hit validation. Axxam  performance-driven approach has been recognized by the clients as key to the success for their discovery programs.  Axxam is also engaged in alliance-based research towards innovative small molecule therapies for diseases with a high unmet medical need. Axxam's business terms are flexible, ranging from fee-for-service to risk-sharing deal structures. LIFE & BRAIN GmbH is a biomedical enterprise founded in 2002 and located at the University Hospital Campus in Bonn, Germany.  As a center of innovation, LIFE & BRAIN acts as a revolving door between academic research and industry. Innovative research results are recognized early and developed further into marketable biomedical products and services. Its mission is to discover and develop novel strategies for the diagnosis and therapy of nervous system disorders. A key focus of LIFE & BRAIN is the development and provision of human pluripotent stem cell-based tools and services for neurological disease modeling and drug discovery. Within the project LIFE & BRAIN will provide induced pluripotent stem cell-derived glial and neuronal populations to model the neuron-glia network in neuropathological pain conditions. King's College London is one of the top 25 universities in the world (2016/17 QS World University Rankings) and among the oldest in England. Research at King's has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and work that led to the development of radio, television, mobile phones and radar. King's has more than 26,500 students from some 150 countries world-wide and nearly 6,900 staff. The university has an outstanding reputation for world-class teaching and cutting-edge research. King's was ranked 6th nationally in the 2014 Research Excellence Framework (REF) and is in the top seven UK universities for research earnings with an overall annual income of more than £600 million. The Natural and Medical Sciences Institute at the University of Tübingen (NMI) is a member of the Innovation Alliance Baden-Württemberg. Its main activities focus on application-oriented research at the interface between life and material sciences. In addition, it also operates as business incubator for start-up companies. NMI unique and interdisciplinary spectrum of skills and competencies, supported by a strong team of more than 150 scientists, provides an ideal research environment where innovative technologies are brought together for the benefit of public stakeholders and industry. A broad range of thematic areas are covered across several departments and laboratories: - Pharma & biotechnology: targets and biomarkers for the identification of active compounds, electrophysiology, diagnostics and bio-analytics Esteve is a leading pharmaceutical chemical group based in Barcelona, Spain. Since it was founded in 1929, Esteve has been firmly committed to excellence in healthcare, dedicating efforts to innovative R&D of new medicines for unmet medical needs and focusing on high science and evidence‐based research. Esteve has a strong partnership approach to drug discovery, development and commercialisation. The company works both independently and in collaboration to bring new, differentiated best‐in‐class treatments to patients. The company currently employs 2,300 professionals and has subsidiaries and production facilities in several European countries, USA, China and Mexico. The Grünenthal Group is an entrepreneurial, science-based pharmaceutical company specialized in pain, gout and inflammation. Our ambition is to deliver four to five new products to patients in diseases with high unmet medical need by 2022 and become a €2 billion company. We are a fully integrated research & development company with a long track record of bringing innovative pain treatments and state-of-the-art technologies to patients. By sustainably investing in our R&D above the industrial average, we are strongly committed to innovation. Grünenthal is an independent, family-owned company headquartered in Aachen, Germany. We are present in 32 countries with affiliates in Europe, Latin America and the US. Our products are sold in more than 155 countries and approx. 5,500 employees are working for the Grünenthal Group worldwide. In 2016, Grünenthal achieved revenues of approx. € 1.4 bn. The Innovative Medicines Initiative (IMI) is working to improve health by speeding up the development of, and patient access to, the next generation of medicines, particularly in areas where there is an unmet medical or social need. It does this by facilitating collaboration between the key players involved in healthcare research, including universities, pharmaceutical companies, and other companies active in healthcare research, small and medium-sized enterprises (SMEs), patient organisations, and medicines regulators. This approach has proven highly successful, and IMI projects are delivering exciting results that are helping to advance the development of urgently-needed new treatments in diverse areas. IMI is a partnership between the European Union and the European pharmaceutical industry, represented by the European Federation of Pharmaceutical Industries and Associations (EFPIA). Through the IMI 2 programme, IMI has a budget of 3.3 bn € for the period 2014-2024. Half of this comes from the EU's research and innovation programme, Horizon 2020. The other half comes from large companies, mostly from the pharmaceutical sector; these do not receive any EU funding, but contribute to the projects 'in kind', for example by donating their researchers' time or providing access to research facilities or resources. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116072. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA Companies. [1]  van Hecke O, Torrance N, Smith BH. Chronic pain epidemiology and its clinical relevance. Br J Anaesth. 2013; 111(1):13-8. [2]  Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain. 2006 Apr;7(4):281-9.


The new research project NGN-PET was launched in the framework of the Innovative Medicine Initiative (IMI), the largest public-private partnership (PPP) for health research worldwide co-funded by the EU and the European pharmaceutical industry. The NGN-PET consortium unites the expertise and knowledge of industry partners from the European Federation of Pharmaceutical Industries and Associations (EFPIA), small and medium-sized enterprises (SMEs) and academia. Together they will investigate neuron-glia interactions aiming to develop authentic cellular (co-culture) assays to discover improved treatments of neuropathic pain using neuronal and glial cell types derived from human induced pluripotent stem cells (iPSC), and their co-cultures. The primary objective is to provide a translational platform for the identification, validation and testing of neuropathic pain targets in preclinical and human-relevant test systems suitable for drug discovery. Chronic pain is a serious debilitating disease which greatly reduces the quality of life for the individual patients. In Europe, 20% of the population are affected which causes considerable socioeconomic burden of over 200 bn € per year[1]. Chronic pain of neuropathic origin has a population prevalence of 8.2%[2]. Neuropathic pain arises after insults such as surgery, trauma, diabetes, chemotherapy or viral infections, and its prevalence is expected to rise in the future due to the ageing society. Current treatments for chronic pain have limited efficacy, leaving about 60% of patients without adequate pain relief[1]. Moreover, these therapies address only symptoms not the causes of the pain, and are therefore not curative. In fact, the aetiologies of the disease are poorly understood which hinders the development of new analgesics with improved efficacies. One of the major findings of the last decade in pain research is that non-neuronal cells play a very active role in the development of sensory abnormalities. In particular, glia - like Schwann cells, microglia, or astrocytes - contribute directly to modulation of neuronal functions. The NGN-PET consortium aims to explore neuron-glial interactions in subtypes of neuropathic pain which are induced by chemotherapy or trauma, and to develop human-predictive test systems that can be implemented in the drug discovery process. These cellular systems will use preclinical tissues and human iPSC-derived neuron-glia co-cultures in novel high-throughput screening platforms. We hope this new science helps in identifying novel more efficacious treatments for neuropathic pain patients. To achieve these ambitious goals, a consortium of 6 partners, with the support of IMI, has been formed. NGN-PET brings together experts from industry, SMEs and academia in a synergistic public-private partnership. NGN-PET is supported by over 3million euros from IMI2 and industry partners in direct and in-kind contributions. The project duration is 3 years. The consortium will disseminate the results through publication in high-impact scientific journals, applying open access policy whenever possible, or in scientific meetings by means of poster or oral presentations. Online outreach of the project publications will be performed via the project website. The NGN-PET project is coordinated by Axxam; the project leader is ESTEVE, supported by Grünenthal as project Co-Leader. Axxam is an innovative Partner Research Organization (iPRO) based in Milan, Italy. Axxam is a leading provider of integrated discovery services across Life Sciences industries including: pharmaceuticals, crop protection, animal health, cosmetics, fragrances, food and beverages. The company has consolidated expertise across a broad range of discovery disciplines and innovative technologies including: assay development, high-throughput screening of both the Axxam high quality compound collections (synthetic and natural) or those provided by our clients, compound management, hit identification and hit validation. Axxam  performance-driven approach has been recognized by the clients as key to the success for their discovery programs.  Axxam is also engaged in alliance-based research towards innovative small molecule therapies for diseases with a high unmet medical need. Axxam's business terms are flexible, ranging from fee-for-service to risk-sharing deal structures. LIFE & BRAIN GmbH is a biomedical enterprise founded in 2002 and located at the University Hospital Campus in Bonn, Germany.  As a center of innovation, LIFE & BRAIN acts as a revolving door between academic research and industry. Innovative research results are recognized early and developed further into marketable biomedical products and services. Its mission is to discover and develop novel strategies for the diagnosis and therapy of nervous system disorders. A key focus of LIFE & BRAIN is the development and provision of human pluripotent stem cell-based tools and services for neurological disease modeling and drug discovery. Within the project LIFE & BRAIN will provide induced pluripotent stem cell-derived glial and neuronal populations to model the neuron-glia network in neuropathological pain conditions. King's College London is one of the top 25 universities in the world (2016/17 QS World University Rankings) and among the oldest in England. Research at King's has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and work that led to the development of radio, television, mobile phones and radar. King's has more than 26,500 students from some 150 countries world-wide and nearly 6,900 staff. The university has an outstanding reputation for world-class teaching and cutting-edge research. King's was ranked 6th nationally in the 2014 Research Excellence Framework (REF) and is in the top seven UK universities for research earnings with an overall annual income of more than £600 million. The Natural and Medical Sciences Institute at the University of Tübingen (NMI) is a member of the Innovation Alliance Baden-Württemberg. Its main activities focus on application-oriented research at the interface between life and material sciences. In addition, it also operates as business incubator for start-up companies. NMI unique and interdisciplinary spectrum of skills and competencies, supported by a strong team of more than 150 scientists, provides an ideal research environment where innovative technologies are brought together for the benefit of public stakeholders and industry. A broad range of thematic areas are covered across several departments and laboratories: - Pharma & biotechnology: targets and biomarkers for the identification of active compounds, electrophysiology, diagnostics and bio-analytics Esteve is a leading pharmaceutical chemical group based in Barcelona, Spain. Since it was founded in 1929, Esteve has been firmly committed to excellence in healthcare, dedicating efforts to innovative R&D of new medicines for unmet medical needs and focusing on high science and evidence‐based research. Esteve has a strong partnership approach to drug discovery, development and commercialisation. The company works both independently and in collaboration to bring new, differentiated best‐in‐class treatments to patients. The company currently employs 2,300 professionals and has subsidiaries and production facilities in several European countries, USA, China and Mexico. The Grünenthal Group is an entrepreneurial, science-based pharmaceutical company specialized in pain, gout and inflammation. Our ambition is to deliver four to five new products to patients in diseases with high unmet medical need by 2022 and become a €2 billion company. We are a fully integrated research & development company with a long track record of bringing innovative pain treatments and state-of-the-art technologies to patients. By sustainably investing in our R&D above the industrial average, we are strongly committed to innovation. Grünenthal is an independent, family-owned company headquartered in Aachen, Germany. We are present in 32 countries with affiliates in Europe, Latin America and the US. Our products are sold in more than 155 countries and approx. 5,500 employees are working for the Grünenthal Group worldwide. In 2016, Grünenthal achieved revenues of approx. € 1.4 bn. The Innovative Medicines Initiative (IMI) is working to improve health by speeding up the development of, and patient access to, the next generation of medicines, particularly in areas where there is an unmet medical or social need. It does this by facilitating collaboration between the key players involved in healthcare research, including universities, pharmaceutical companies, and other companies active in healthcare research, small and medium-sized enterprises (SMEs), patient organisations, and medicines regulators. This approach has proven highly successful, and IMI projects are delivering exciting results that are helping to advance the development of urgently-needed new treatments in diverse areas. IMI is a partnership between the European Union and the European pharmaceutical industry, represented by the European Federation of Pharmaceutical Industries and Associations (EFPIA). Through the IMI 2 programme, IMI has a budget of 3.3 bn € for the period 2014-2024. Half of this comes from the EU's research and innovation programme, Horizon 2020. The other half comes from large companies, mostly from the pharmaceutical sector; these do not receive any EU funding, but contribute to the projects 'in kind', for example by donating their researchers' time or providing access to research facilities or resources. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116072. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA Companies. [1]  van Hecke O, Torrance N, Smith BH. Chronic pain epidemiology and its clinical relevance. Br J Anaesth. 2013; 111(1):13-8. [2]  Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain. 2006 Apr;7(4):281-9.


Gonzalez-Cano R.,University of Granada | Merlos M.,Esteve | Baeyens J.M.,University of Granada | Cendan C.M.,University of Granada
Anesthesiology | Year: 2013

Background: Visceral pain is an important and prevalent clinical condition whose treatment is challenging. Sigma-1 (σ1) receptors modulate somatic pain, but their involvement in pure visceral pain is unexplored. Methods: The authors evaluated the role of σ1 receptors in intracolonic capsaicin-induced visceral pain (pain-related behaviors and referred mechanical hyperalgesia to the abdominal wall) using wild-type (WT) (n = 12 per group) and σ1 receptor knockout (σ1- KO) (n = 10 per group) mice, selective σ1 receptor antagonists (BD-1063, S1RA, and NE-100), and control drugs (morphine and ketoprofen). Results: The intracolonic administration of capsaicin (0.01-1%) induced concentration-dependent visceral pain-related behaviors and referred hyperalgesia in both WT and σ1-KO mice. However, the maximum number of pain-related behaviors induced by 1% capsaicin in σ1- KO mice (mean ± SEM, 22 ± 2.9) was 48% of that observed in WT animals (46 ± 4.2). Subcutaneous administration of the σ1 receptor antagonists BD-1063 (16-64 mg/kg), S1RA (32-128 mg/kg), and NE-100 (8-64 mg/kg) dose-dependently reduced the number of behavioral responses (by 53, 62, and 58%, respectively) and reversed the referred hyperalgesia to mechanical control threshold (0.53 ± 0.05 g) in WT mice. In contrast, these drugs produced no change in σ1-KO mice. Thus, the effects of these drugs are specifically mediated by σ1 receptors. Morphine produced an inhibition of capsaicin-induced visceral pain in WT and σ1-KO mice, whereas ketoprofen had no effect in either mouse type. Conclusion: These results suggest that σ1 receptors play a role in the mechanisms underlying capsaicin-induced visceral pain and raise novel perspectives for their potential therapeutic value. © 2013, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.


Pallicer J.M.,University of Barcelona | Calvet C.,ESTEVE | Port A.,ESTEVE | Roses M.,University of Barcelona | And 2 more authors.
Journal of Chromatography A | Year: 2012

A reorted chromatographic method to determine the 1-octanol/water partition coefficient (logP o/w) has been used to estimate the lipophilicity of 33 drugs with diverse structures and functionalities, including neutral, acid, basic, and amphoteric compounds. The applicability of the chromatographic method has been extended to the UHPLC technique, and the results obtained were compared to those obtained from conventional HPLC. No significant difference between the results obtained by both techniques is noticed. Thus, the suitability of UHPLC, which involves shorter run times, for lipophilicity assessment is demonstrated. In order to show the consistency of this chromatographic method, the logP o/w values of those drugs which have acid-base properties have been also determined by potentiometry, and the final results have been compared with both values derived from the chromatographic method and the ones from the literature. © 2012 Elsevier B.V.


Bura A.S.,University Pompeu Fabra | Guegan T.,University Pompeu Fabra | Zamanillo D.,Esteve | Vela J.M.,Esteve | Maldonado R.,University Pompeu Fabra
European Journal of Pain (United Kingdom) | Year: 2013

Background: The treatment of neuropathic pain is unsatisfactory at the present moment and the sigma 1 receptor has been identified as a new potential target for neuropathic pain. The aim of this study was to use an operant self-administration model to reveal the potential interest of a new sigma 1 receptor antagonist, S1RA, in chronic pain that was developed in mice by a partial ligation of the sciatic nerve. Methods: Once that chronic pain had reached a steady state, mice were trained to maintain an operant behaviour to self-administer S1RA. The possible abuse liability of the analgesic compound was determined by evaluating operant self-administration in sham-operated mice. The influence of S1RA on the anhedonic state related to chronic pain was also evaluated by measuring the preference for palatable drink (2% sucrose solution) using a recently validated and highly sensitive behavioural device. Results: Nerve-injured mice, but not sham-operated animals, acquired the operant responding to obtain S1RA (6 mg/kg/infusion). After 10 days of S1RA self-administration, neuropathic pain was significantly reduced in nerve-injured mice. In addition, an anhedonic state was revealed in nerve-injured mice by a decreased consumption of palatable drink, which was significantly attenuated by S1RA (25 mg/kg). Conclusions: These results reveal the analgesic efficacy of the sigma antagonist, S1RA, in neuropathic pain associated with an improvement of the emotional negative state and that was devoided of reinforcing effects. The operant responses evaluated in this new mouse model can have a high predictive value to estimate the clinical benefit/risk ratio of new analgesic compounds to treat chronic pain, such as S1RA. © 2012 European Federation of International Association for the Study of Pain Chapters.


Vela J.M.,ESTEVE | Merlos M.,ESTEVE | Almansa C.,ESTEVE
Expert Opinion on Investigational Drugs | Year: 2015

Introduction: The sigma-1 receptor (σ1R) is a ligand-regulated molecular chaperone that interacts with other proteins, including NMDA and opioid receptors, to modulate their activity. Convergent evidence indicates that σ1R antagonists exert inhibitory effects (and agonists stimulatory effects) on pain by stepping down the intracellular signaling cascades involved in transduction of noxious stimuli and plastic changes (i.e., sensitization phenomena) associated with chronic pain states. Areas covered: This review addresses three primary domains. The first focuses on mechanisms underlying the antinociceptive effects of σ1R antagonists. The second addresses evidence gained using pharmacological tools and experimental drugs in the discovery phase and clinical development. Finally, the article outlines the potential benefits of σ1R antagonists, alone or in combination, in the context of available pain therapeutics. Expert opinion: There is a critical need for new analgesics based on new mechanisms of action. Target identification requires convincing evidence relating targets to function. In turn, target validation requires confirmation of therapeutic benefits, ideally in humans. Current preclinical evidence provides strong rationale for σ1R antagonists in pain. The outcome of clinical studies with the most advanced investigational σ1R antagonist, S1RA (E-52862), will be of great interest to ascertain the potential of this new therapeutic approach to pain management. © 2015 Informa UK, Ltd.


Schlager T.,University of Munster | Schepmann D.,University of Munster | Lehmkuhl K.,University of Munster | Holenz J.,Esteve | And 3 more authors.
Journal of Medicinal Chemistry | Year: 2011

The novel class of spirocyclic σ 1 ligands 3 (6′,7′-dihydro-1′H-spiro[piperidine-4,4′-pyrano[4,3-c] pyrazoles]) was designed by the combination of the potent σ 1 ligands 1 and 2 in one molecule. Thorough structure affinity relationships were derived by the variation of the substituents in position 1′, 1, and 6′. Whereas the small electron rich methylpyrazole heterocycle was less tolerated by the σ 1 receptor protein, the introduction of a phenyl substituent instead of the methyl group led to ligands with a high σ 1 affinity. It is postulated that the additional phenyl substituent occupies a previously unrecognized hydrophobic region of the σ 1 receptor resulting in additional lipophilic interactions. The spirocyclic pyranopyrazoles are very selective against the σ 2 subtype, the PCP binding site of the NMDA receptor, and further targets. Despite high σ 1 affinity, the cyclohexylmethyl derivative 17i (K i (σ 1) = 0.55 nM) and the isopentenyl derivative 17p (K i (σ 1) = 1.6 nM) showed only low antiallodynic activity in the capsaicin assay. © 2011 American Chemical Society.

Loading ESTEVE collaborators
Loading ESTEVE collaborators