Modelo de negocios en la salud e investigación clínica: la cuestión de las patentes en la ciencia

Propósito/Contexto. En este artículo se exponen las tendencias y las características de un modelo de negocio que la industria farmacéutica ha venido imponiendo con la ayuda del desarrollo de nuevos medicamentos a los que se les cuestiona su "altura inventiva" y que, a pesar de ello, les son otorgadas las patentes de segunda generación, considerándose esta una práctica abusiva y que favorece el incremento de los precios de estas innovaciones en el mercado. Metodología/Enfoque. Mediante la presentación de un caso: "la declaración de interés público del medicamento imatinib en Colombia" se identifican las estrategias y las maniobras anticompetitivas que dejan pocas oportunidades a los Estados para distribuir de manera equitativa los beneficios de las invenciones de medicamentos. En el análisis bioético del caso se caracteriza el dilema como tipo práctico, esto es, aquel en el que persisten requerimientos morales en tensión con un interés privado, en esta ocasión, entre la salud pública, por un lado, y la propiedad intelectual como política internacional, por el otro. Resultados/Hallazgos. La tesis es que este es un problema transfronterizo sintomático de la falta de justicia global en razón a la suplantación del sentido de "bien común" que ha acallado los vínculos sociales, solidarios y colaborativos. Discusión/Conclusiones/Contribuciones. Se insta a un consenso sobre las bases sociales y el respeto de la dignidad de las personas, un mandato de solidaridad superior en beneficio del bien común y el "florecimiento de la humanidad".

Objetivo/Contexto. Este artigo expõe as tendências e características de um modelo de negócio que a indústria farmacêutica tem vindo a impor com a ajuda do desenvolvimento de novos medicamentos cujo nível de inventividade é questionado. Como resultado, é-lhes concedidas patentes de segunda geração, o que é considerado uma prática abusiva e favorece o aumento dos preços destes inovações no mercado. Metodologia/Abordagem. Através da apresentação de um caso "A Declaração de Interesse Público da droga Imatinib na Colômbia", são identificadas estratégias e manobras anticompetitivas, que deixam poucas oportunidades para os Estados distribuírem os benefícios das invenções de drogas de forma equitativa. Na análise bioética do caso, o dilema é especificado como sendo prático, ou seja, um dilema em que os requisitos morais persistem em tensão com um interesse privado, neste caso, entre a saúde pública, por um lado, e a propriedade intelectual como uma política internacional, por outro. Resultados/Descobertas. A tese é que se trata de um problema transfronteiriço sintomático de falta de justiça global devido à suplência de um senso o bem comum que silenciou os laços sociais de solidariedade e colaboração. Discussão/Conclusões/Contribuições. Apela a um consenso sobre os fundamentos sociais e o respeito pela dignidade das pessoas, um mandato de maior solidariedade em benefício do bem comum, o florescimento da humanidade.

Purpose/Background. This article exposes the tendencies and characteristics of a business model that the pharmaceutical industry has been imposing with the help of the development of new drugs whose degree of inventiveness is questioned. As a result, they are granted second generation patents, which is considered an abusive practice that favors the increase of the prices of these innovations in the market. Methodology/Approach. Through the presentation of a case "The Declaration of Public Interest of the Drug Imatinib in Colombia", anti-competitive stra-tegies and maneuvers are identified, which leave few opportunities for the States to distribute the benefits of drug inventions in an equitable manner. In the bioethical analysis of the case, the dilemma is specified as a practical one, that is, one in which moral requirements persist in tension with a private interest, in this case, between public health on the one hand, and intellectual property as an international policy, on the other. Results/Findings. The thesis is that this is a cross-border problem symptomatic of a lack of global justice due to the supplanting of the sense of the common good that has silenced social bonds of solidarity and collaboration. Discussion/Conclusions/Contributions. It calls for a consensus on social foundations and respect for the dignity of persons, a higher mandate of solidarity for the benefit of the common good, and the flourishing of humanity.

A nanoemulsion-based delivery system for imatinib and in vitro anticancer efficacy

A self-nanoemulsifying drug delivery system (SNEDDS) composed of ethyl oleate, Tween 80 and polyethylene glycol 600 was prepared as a new route to improve the efficacy of imatinib. The drug-loaded SNEDDS formed nanodroplets of ethyl oleate stabilized by Tween 80 and polyethylene glycol 600 with a diameter of 81.0±9.5 nm. The nanoemulsion-based delivery system was stable for at least two months, with entrapment efficiency and loading capacity of 16.4±0.1 and 48.3±0.2%, respectively. Imatinib-loaded SNEDDS was evaluated for the drug release profiles, and its effectiveness against MCF-7 cell line was investigated. IC50 values for the imatinib-loaded SNEDDS and an imatinib aqueous solution were 3.1 and 6.5 µg mL-1, respectively.

Tumor estromal gastrointestinal de origem gástrica: relato de caso / Gastrointestinal stromal tumor of gastric origin: case report

Os tumores estromais gastrintestinais (GIST) são raros, de comportamento imprevisível, sendo a maioria assintomática ou com sintomas inespecíficos. Podem acometer qualquer local do tubo digestivo, sendo o tratamento padrão a ressecção cirúrgica completa, porém são frequentes as recidivas e metástases. O presente caso é um relato de uma paciente idosa com massa abdominal crescente e dolorosa ao exame físico, com resultado de exames complementares de imagem que sugerem tratar-se de GIST. Submetida à terapia cirúrgica para ressecção da lesão e seguimento com mesilato de imatinibe (Glivec®). (AU)

Gastrointestinal stromal tumors (GIST) are rare, with unpredictable behavior, most of them asymptomatic or nonspecific symptoms. They may arise in any place of digestive tube, and the standard treatment is the complete surgical resection, however recurrences and metastases are frequent. The following case is a report from an elderly patient with growing and painful abdominal mass on physical examination, and the result of complementary imaging tests suggests that this is GIST. Submitted to surgical therapy for resection of the lesion and follow-up with imatinib mesylate (Glivec®). (AU)

Effects of glivec combined with everolimus on mouse pituitary AtT-20 cells / 医学研究生学报

Objective Medication for pituitary adenomas is mainly targeted on the prolactin-secreting and growth-hormone types and shows poor therapeutic effects on other adenomas .Therefore, new drugs urgently need to be developed for this purpose .This study was to investigate the effects of glivec and everolimus on mouse pituitary AtT-20 cells and their molecular mechanisms in vitro. Methods Mouse pituitary AtT-20 cells were incubated with glivec or everolimus or combination of both and their inhibitory effect on the proliferation of the cells was measured by CCK-8 assay.The mRNA levels of AKT and ERK were determined by q-PCR and the ex-pressions of the phosphorylated AKT (p-AKT) and ERK (p-ERK) were detected by Western blot. Results Used alone, both glivec and everolimus inhibited the proliferation of the AtT-20 cells in a time-and dose-dependent manner , but their combination produced a mutually antagonistic effect, with combination index values of 1.13 ±0.06, 1.12 ±0.03, and 1.07 ±0.03 respectively.The two a-gents , either used alone or in combination , induced no significantly inhibitory effects on the mRNA and protein expressions of AKT and ERK ( P >0.05 ).Both glivec and everolimus up-regulated the expressions of p-AKT and p-ERK, and their combination manifested an even stronger effect (P>0.05). Conclusion Both glivec and everolimus inhibit the proliferation of AtT-20 cells when administered alone, but their combination produces an antagonistic effect .Their action mechanism might be that when targeting some signaling path-ways to inhibit cell proliferation , glivec, as well as everolimus , in-duces a feedback activation of AKT and ERK .

Three cases of Philadelphia (Ph) chromosome positive acute myeloid leukemia (AML) treated with imatinib mesylate (Glivec, STI571) and allogeneic hematopoietic stem cell transplantation after induction chemotherapy / 대한내과학회지

The Ph-chromosome is the hallmark of chronic myelogenous leukemia (CML), but it has also been reported infrequently for de novo AML. This cytogenetic variant of AML is characterized by a poor prognosis associated with extraordinary drug resistance. Experience with the use of imatinib mesylate for Ph-chromosome-positive de novo AML is limited because of the rarity of the disorder. Thus, allogeneic hematopoietic stem cell transplantation (HSCT), as a post-remission therapy, should be considered. In three patients with Ph-chromosome-positive AML, we achieved complete remission with induction chemotherapy and the use of an imatinib cycle as an interim therapy. Subsequently, all patients received consolidation chemotherapy followed by imatinib cycles, bridging the time to allogeneic HSCT. All patients were successfully transplanted, and have been in excellent condition, with a median follow-up duration of 15 months (range, 2-25 months). We report on these cases and present the treatment strategy of induction chemotherapy, maintenance with imatinib mesylate, and final allogeneic HSCT as a representative paradigm for the treatment of Ph-chromosome-positive de novo AML.

Effect of Imatinib Mesylate in Recurrent Gastric GIST

PURPOSE: Gastrointestinal stromal tumor (GIST) is the designation for c-kit signal driven mesenchymal tumor. A great majority of these tumors occur in the stomach and small intestine, and rarely in the colon, rectum and esophagus. Metastatic or recurrent GIST must be resected surgically because it is resistant to conventional cytotoxic chemotherapy. Following recent evidence for the dramatic effect of Imatinib mesylate (Glivec), Glivec has become available in our country since June 2001 without insurance coverage. Although some doubt remained, we applied Glivec to recurrent GIST patients with great expectation. METHODS: A retrospective analysis was made for 16 GIST patients who were resected during 2001. Follow up duration was 19 to 29 months. All pathologic slides were reexamined immunohistochemically by an experienced pathologist. Clinicopathologic comparison between the recurred and non-recurred groups was summarized into the tables. The therapeutic and side effects of Glivec were surveyed. CT scan files were reviewed to decided tumor regression or progression. RESULTS: Fifteen GISTs were resected in 2001. Seven cases recurred during 19 to 29 months of follow up. The recurred group was characterized by huge tumor size (mean 14 cm), serosal invasion and more than 10 mitosis in 50 HPF. A daily dose of 400 mg of Glivec was prescribed to every recurred GIST patients and CT scan was followed serially. The therapeutic effect of Glivec effect was drastic but variable; complete tumor remission (n=3), rebounded tumor growth at the same location after remission (n=1), and recurrence at another location after complete remission (n=2). CONCLUSION: Glivec drastically reduced the size of recurrent gastric GIST initially. However, it is not clear how long Glivec should be taken at a great expense in fear of rebounded growth after abstaining. It appears that reoperation is necessary without delay when tumor remission slows down.