WO2014089646A1 - Use of products from paullinia cupana to prevent or treat hot flushes - Google Patents
Use of products from paullinia cupana to prevent or treat hot flushes Download PDFInfo
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- WO2014089646A1 WO2014089646A1 PCT/BR2012/000514 BR2012000514W WO2014089646A1 WO 2014089646 A1 WO2014089646 A1 WO 2014089646A1 BR 2012000514 W BR2012000514 W BR 2012000514W WO 2014089646 A1 WO2014089646 A1 WO 2014089646A1
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- the present invention relates to the use of Paullinia cupana products in the preparation of medicaments for the prevention or treatment of hot flushes, particularly related to cancers and menopause. Also subject to the present invention are medicines containing the same and method for treating hot flushes.
- Hot flashes are defined as transient periods of intense heat in the upper body, arms and face, often accompanied by flushing, vasodilation, sweating, anxiety, irritability, insomnia, depression, change in concentration and increased frequency. heart
- Hot flushes are common in breast cancer patients, affecting about two thirds of them, and may contribute to the aggravation of other unwanted occurrences such as fatigue, depression, anxiety, sleep and quality of life. It also affects a high percentage (over 50%) of women in the transition period to menopause.
- Intensity, duration and persistence vary among patients and seem to be influenced by emotional changes such as anxiety or stress, systemic diseases, neurological disorders, food and drink intake, especially alcohol and drugs, among others.
- thermoregulatory center and hormone levels have already been pointed out.
- Predisposing factors were studied in addition to hormonal levels, race, body mass index, smoking, tubal ligation and surgical menopause.
- Figure 1 shows the measurement of hot flushes per day after a study with 15 patients who took guarana powder.
- Figure 2 shows the severity score per week throughout the study for the same group of patients.
- the present invention relates to the use of Paullinia cupana (guarana) product products in the prevention or treatment, as well as the preparation of medicaments for the prevention or treatment of hot flushes, particularly related to cancer and menopause.
- “Paullinia cupana products” include, without limitation, derivatives obtained directly or indirectly from any part of the plant, including leaves, fruits or roots.
- the present invention contemplates as a product of Paullinia cupana, guarana powder, obtained by methods known to the man of the art, which employ the milling of Paullinia cupana seed, which has been previously roasted and peeled, as mentioned in Publication by Oliveira J ⁇ nior et al: Regional Potentials Project, Economic Feasibility Study, Guarana, ISAE Higher Institute of Administration and Economics / Get ⁇ lio Vargas Foundation (FGV), 2003, incorporated herein by reference.
- the present invention also contemplates as a product of Paullinia cupana active fractions derived from Paullinia cupana or Paullinia cupana seed powder.
- the present invention contemplates an active fraction of Paullinia cupana containing an average theobromine content ranging from about 0.05 to about 1 wt%, particularly about 0.1 wt%, and particularly about 10 to about 20% by weight of caffeine as described in International Patent Application WO2012129629, incorporated herein by reference.
- hot flushes are transient episodes of intense heat.
- treatment efficacy is meant that the number of these episodes should decrease by at least 50% with a given treatment, as well as their intensity.
- Paullinia cupana product may be supplied directly to the patient or may be delivered in appropriate pharmaceutical
- the present invention also relates to pharmaceutical compositions containing the active moiety according to the present invention or medicaments containing the same.
- compositions according to the present invention may be liquid, semi-solid or solid and may be adapted for any enteral or parenteral administration route, with immediate or modified release.
- said pharmaceutical composition is adapted for oral administration, particularly in the form of tablets or capsules.
- Suitable pharmaceutically acceptable excipients according to the present invention are, for example and without limitation, those cited in Remington's Pharmaceutical Sciences, Mack Publishing, American or European Pharmacopoeia or Brazilian Pharmacopoeia.
- the present invention further relates to a method for the prevention or treatment of hot flushes, particularly cancer or menopause, which is to provide a Paullinia cupana product according to the present invention to a patient in need.
- An amount of the active fraction according to the present invention was prepared using 2 kg of guarana powder.
- the guarana powder was extracted on a mechanical stirrer with 4 liters of a mixture of ethanol and 70:30 water for 1 hour at full speed.
- the obtained product was filtered through a Buckner funnel, obtaining the first intermediate fraction.
- the filter residue was then extracted with 2 liters of 70:30 ethanol and water for 1 hour at full speed.
- the obtained product was filtered, also in a Buckner funnel, obtaining the second intermediate fraction.
- the two intermediate fractions were mixed and dried on a rotary evaporator, yielding about 500 grams of the active fraction according to the present invention.
- the 500 grams of the active fraction according to the present invention was subjected to HPLC analysis (High Performance Liquid Chromatography) to determine the theobromine and caffeine contents.
- the analytical curve was prepared by weighing about 10 mg of the theobromine and caffeine analytical standards in 25 mL volumetric flasks and bulging with the mobile phase. From these stock solutions, successive dilutions were made to construct the analytical curve for the standards, filtered through 0.45 ⁇ membrane and injected into a chromatograph.
- the samples were prepared by analytically weighing about 50mg of the sample in a 25mL volumetric flask and completing the volume with the mobile phase, filtering through 0.45 ⁇ membrane and injecting into the chromatograph.
- LC-DAD Waters Alliance LC-DAD system consisting of 2695 pump, column heater, 2996 diode array detector and Empower ® software (Empower Software Solutions, Inc, US).
- the average content of theobromine in the active fraction sample according to the present invention was 0.096% and the average caffeine content was 16.16%.
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Abstract
Description
USO DE PRODUTOS DE PAULLINIA CUPANA NA PREVENÇÃO OU TRATAMENTO USE OF PAULLINIA CUPANA PRODUCTS IN PREVENTION OR TREATMENT
DE FOGACHO FOGACHO
Campo da Invenção Field of the Invention
A presente invenção refere-se ao uso de produtos de Paullinia cupana na preparação de medicamentos para prevenção ou tratamento de fogachos, particularmente relacionados aos cânceres e à menopausa. Também é objeto da presente invenção medicamentos contendo o mesmo e método para tratar fogacho. The present invention relates to the use of Paullinia cupana products in the preparation of medicaments for the prevention or treatment of hot flushes, particularly related to cancers and menopause. Also subject to the present invention are medicines containing the same and method for treating hot flushes.
Fundamentos da Invenção Background of the Invention
Fogachos, ou ondas de calor, são definidos como períodos transitórios de intenso calor, na parte superior do corpo, braços e face, frequentemente acompanhados de enrubescimento, vasodilatação, sudorese, ansiedade, irritabilidade, insónia, depressão, alteração de concentração e aumento da frequência cardíaca. Hot flashes, or hot flashes, are defined as transient periods of intense heat in the upper body, arms and face, often accompanied by flushing, vasodilation, sweating, anxiety, irritability, insomnia, depression, change in concentration and increased frequency. heart
Os fogachos são comuns em pacientes com câncer de mama, afetando cerca de dois terços deles, podendo contribuir para o agravamento de outras ocorrências indesejadas como fadiga, depressão, ansiedade, sono e qualidade de vida. Acomete também um percentual elevado (mais de 50%) das mulheres no período de transição para a menopausa. Hot flushes are common in breast cancer patients, affecting about two thirds of them, and may contribute to the aggravation of other unwanted occurrences such as fatigue, depression, anxiety, sleep and quality of life. It also affects a high percentage (over 50%) of women in the transition period to menopause.
A intensidade, duração e persistência variam entre pacientes e parecem ser influenciadas por alteração emocional, como ansiedade ou estresse, doenças sistémicas, distúrbios neurológicos, ingestão de alimentos e bebida, em especial álcool e drogas, entre outros. Intensity, duration and persistence vary among patients and seem to be influenced by emotional changes such as anxiety or stress, systemic diseases, neurological disorders, food and drink intake, especially alcohol and drugs, among others.
Apesar de acometer um número grande de mulheres, em diversas etapas da vida, poucos estudos investigaram sua etiologia e fatores predisponentes. Já foram apontadas, como possíveis fatores etiológicos, as alterações no centro termorregulador e nos níveis hormonais. Como fatores predisponentes foram estudados, além dos níveis hormonais, raça, índice de massa corporal, tabagismo, laqueadura tubária e menopausa cirúrgica. Despite affecting a large number of women at various stages of life, few studies have investigated their etiology and predisposing factors. As possible etiological factors, changes in the thermoregulatory center and hormone levels have already been pointed out. As factors Predisposing factors were studied in addition to hormonal levels, race, body mass index, smoking, tubal ligation and surgical menopause.
Seu diagnóstico também limitado, sendo resultado de estudo do histórico de saúde do paciente e de sua descrição sobre os calores. Its diagnosis is also limited, resulting from a study of the patient's health history and his description of the heat.
Por essas razões, atualmente, o tratamento dos fogachos também é bastante restrito, sendo utilizados hormônios (estrogênios , progestagênios ) , clonidina, veralipride, antidepressivos (fluoxetina, paroxetina, venlafaxina) , vitamina E e/ou isoflavona de soja. Vale mencionar que mulheres portadoras de câncer de mama com fogachos não podem receber reposição hormonal para seu tratamento e que várias das medicações supramencionadas podem ainda interferir com medicações prescritas para o tratamento do câncer de mama como, por exemplo, o Tamoxifeno . For these reasons, currently, the treatment of hot flushes is also very restricted, using hormones (estrogens, progestogens), clonidine, veralipride, antidepressants (fluoxetine, paroxetine, venlafaxine), vitamin E and / or soy isoflavone. It is worth mentioning that women with hot flashes of breast cancer cannot receive hormone replacement for their treatment and that several of the above mentioned medications may still interfere with prescribed breast cancer medications such as Tamoxifen.
Assim, embora algumas poucas as formas de controle de fogacho estejam atualmente disponíveis, seu manejo ainda representa um desafio, persistindo a necessidade de uma alternativa efetiva em sua prevenção e tratamento. Thus, although a few forms of control of hot flushes are currently available, their management is still a challenge, and the need for an effective alternative for prevention and treatment persists.
Breve Descrição das Figuras Brief Description of the Figures
A figura 1 apresenta a medida de fogachos por dia ao logo de estudo realizado com 15 pacientes que tomaram pó de guaraná. Figure 1 shows the measurement of hot flushes per day after a study with 15 patients who took guarana powder.
A figura 2 apresenta o escore de severidade por semana ao longo do estudo em relação ao mesmo grupo de pacientes . Figure 2 shows the severity score per week throughout the study for the same group of patients.
Descrição da Invenção Description of the Invention
A presente invenção tem por objeto o uso de produtos de produtos de Paullinia cupana (guaraná) na prevenção ou tratamento, bem como preparação de medicamentos para prevenção ou tratamento, de fogachos, particularmente relacionados aos cânceres e à menopausa. The present invention relates to the use of Paullinia cupana (guarana) product products in the prevention or treatment, as well as the preparation of medicaments for the prevention or treatment of hot flushes, particularly related to cancer and menopause.
De acordo com a presente invenção, "produtos de Paullinia cupana" incluem, sem qualquer limitação, derivados obtidos, direta ou indiretamente, de quaisquer partes da planta, incluindo folhas, frutos ou raízes. According to the present invention, "Paullinia cupana products" include, without limitation, derivatives obtained directly or indirectly from any part of the plant, including leaves, fruits or roots.
Em realização particular, a presente invenção contempla como produto de Paullinia cupana, o pó de guaraná, obtido por processos conhecidos do homem da técnica, que empregam a moagem da semente de Paullinia cupana, a qual foi previamente torrada e descascada, tal como mencionado na publicação de Oliveira Júnior et al: projeto potencialidades regionais , estudo de viabilidade económica , guaraná, Instituto Superior de Administração e Economia ISAE/Fundação Getúlio Vargas (FGV), 2003, aqui incorporado como referência . In particular embodiment, the present invention contemplates as a product of Paullinia cupana, guarana powder, obtained by methods known to the man of the art, which employ the milling of Paullinia cupana seed, which has been previously roasted and peeled, as mentioned in Publication by Oliveira Júnior et al: Regional Potentials Project, Economic Feasibility Study, Guarana, ISAE Higher Institute of Administration and Economics / Getúlio Vargas Foundation (FGV), 2003, incorporated herein by reference.
Em outra realização particular, a presente invenção também contempla como produto de Paullinia cupana, frações ativas provenientes de Paullinia cupana ou do pó da semente de Paullinia cupana. Em realização ainda mais particular, a presente invenção contempla uma fração ativa de Paullinia cupana que contém teor médio de teobromina variando entre cerca de 0,05 a cerca de 1% em peso, particularmente cerca de 0,1% em peso e, particularmente, cerca de 10 a cerca de 20% em peso de cafeína, tal como descrita no pedido de patente internacional WO2012129629, aqui incorporado como referência. In another particular embodiment, the present invention also contemplates as a product of Paullinia cupana active fractions derived from Paullinia cupana or Paullinia cupana seed powder. In a still more particular embodiment, the present invention contemplates an active fraction of Paullinia cupana containing an average theobromine content ranging from about 0.05 to about 1 wt%, particularly about 0.1 wt%, and particularly about 10 to about 20% by weight of caffeine as described in International Patent Application WO2012129629, incorporated herein by reference.
De acordo com a presente invenção, entende-se por "fogachos" episódios transitórios de intenso calor. Por "eficácia de tratamento" entende-se que o numero destes episódios deva diminuir pelo menos em 50% com um dado tratamento, assim como sua intensidade. According to the present invention, "hot flushes" are transient episodes of intense heat. By "treatment efficacy" is meant that the number of these episodes should decrease by at least 50% with a given treatment, as well as their intensity.
0 produto de Paullinia cupana pode ser fornecido diretamente ao paciente ou ser veiculado em formas farmacêuticas apropriadas. Assim, a presente invenção também está relacionada a composições farmacêuticas contendo a fração ativa de acordo com a presente invenção ou medicamentos contendo a mesma. Paullinia cupana product may be supplied directly to the patient or may be delivered in appropriate pharmaceutical Thus, the present invention also relates to pharmaceutical compositions containing the active moiety according to the present invention or medicaments containing the same.
As composições farmacêuticas de acordo com a presente invenção podem ser liquidas, semissólidas ou sólidas e podem ser adaptadas para qualquer via de administração enteral ou parenteral, com liberação imediata ou modificada. Em realização particular, a dita composição farmacêutica é adaptada para a administração oral, particularmente na forma de comprimidos ou capsulas. The pharmaceutical compositions according to the present invention may be liquid, semi-solid or solid and may be adapted for any enteral or parenteral administration route, with immediate or modified release. In particular embodiment, said pharmaceutical composition is adapted for oral administration, particularly in the form of tablets or capsules.
Os excipientes farmaceuticamente aceitáveis apropriados de acordo com a presente invenção são, por exemplo e sem limitação, aqueles citados no livro Remington's Pharmaceutical Sciences, editora Mack Publishing, Farmacopéia Americana ou Europeia ou Farmacopéia Brasileira . Suitable pharmaceutically acceptable excipients according to the present invention are, for example and without limitation, those cited in Remington's Pharmaceutical Sciences, Mack Publishing, American or European Pharmacopoeia or Brazilian Pharmacopoeia.
A presente invenção refere-se ainda a um método para prevenção ou tratamento de fogachos, particularmente relacionada aos cânceres ou à menopausa, que consiste em fornecer um produto de Paullinia cupana de acordo com a presente invenção a um paciente necessitado. The present invention further relates to a method for the prevention or treatment of hot flushes, particularly cancer or menopause, which is to provide a Paullinia cupana product according to the present invention to a patient in need.
A presente invenção é adicionalmente ilustrada pelos seguintes exemplos não limitadores. The present invention is further illustrated by the following nonlimiting examples.
EXEMPLO 1 EXAMPLE 1
TESTE DE EFICÁCIA COM PÓ DE GUARANÁ GUARANÁ POWDER EFFICIENCY TEST
O estudo foi realizado em mulheres com câncer de mama pelo menos três meses após terminar cirurgia, radiação e quimioterapia, com pelo menos quatorze fogachos por semana durante pelo menos um mês antes da inclusão. Foram excluídas as pacientes que receberam reposição hormonal. Foi permitida a participação de doentes que receberam estrogênio à base de cremes vaginais ou antidepressivos prescritos para pelo menos um mês anterior à inclusão. As pacientes receberam 50 mg de pó de guaraná, duas vezes por dia, durante seis semanas após o inicio de uma semana, sem tratamento. Foi avaliada a frequência dos fogachos e sua gravidade. As pacientes classificaram suas próprias reações de toxicidade semanalmente. Utilizou-se a fase II de design Simon em que nove em cada quinze pacientes seria necessário ter, pelo menos, uma redução de 50% na sua pontuação de gravidade da insuficiência cardíaca, a fim de continuar o estudo. The study was conducted on women with breast cancer at least three months after surgery, radiation, and chemotherapy, with at least fourteen hot flushes a week for at least one month before inclusion. Patients who received hormone replacement were excluded. Patients who were given estrogen-based vaginal creams or antidepressants prescribed for one month prior to inclusion. The patients received 50 mg of guarana powder twice a day for six weeks after the start of one week without treatment. The frequency of hot flushes and their severity were evaluated. The patients rated their own toxicity reactions weekly. Design phase II Simon was used in which nine out of every fifteen patients would need to have at least a 50% reduction in their heart failure severity score in order to continue the study.
RESULTADOS RESULTS
Foram incluídas no estudo 24 mulheres pós- menopausadas , que tiveram câncer, com queixas de fogachos. Apenas quinze completaram as seis semanas do estudo. Dez das quinze pacientes tiveram uma redução de mais de 50% em seu escore de gravidade. Ao longo das seis semanas de tratamento observou-se uma diminuição estatisticamente significativa no número de fogachos (p = 0.0033) e escores de gravidade (p =0.0039). Em comparação com a semana 0, os pacientes relataram agravamento da anorexia (1), a insónia (1), náusea (1) , fadiga (1), transpiração (1), constipação (1), ansiedade (1), alteração do humor (1) e dor de cabeça (1). Nenhuma destas toxicidades justificou a interrupção do estudo . Twenty-four postmenopausal women who had cancer with complaints of hot flushes were included in the study. Only fifteen completed the six weeks of the study. Ten of the fifteen patients had a more than 50% reduction in their severity score. Over the six weeks of treatment there was a statistically significant decrease in the number of hot flushes (p = 0.0033) and severity scores (p = 0.0039). Compared to week 0, patients reported worsening anorexia (1), insomnia (1), nausea (1), fatigue (1), sweating (1), constipation (1), anxiety (1), mood (1) and headache (1). None of these toxicities warranted discontinuation of the study.
Portanto, observa-se que o uso de produto de Paullinia cupana é eficaz no controle de fogacho, com toxicidade aceitável. Therefore, it is observed that the use of Paullinia cupana product is effective in controlling hot flushes with acceptable toxicity.
EXEMPLO 2 EXAMPLE 2
PREPARAÇÃO DA FRAÇÃO ATIVA DE PAULLINIA CUPANA PREPARATION OF PAULLINIA CUPANA'S ACTIVE FRACTION
Uma quantidade da fração ativa de acordo com a presente invenção foi preparada utilizando-se 2 Kg de pó de guaraná . An amount of the active fraction according to the present invention was prepared using 2 kg of guarana powder.
0 pó de guaraná foi submetido à extração, em um agitador mecânico, com 4 litros de uma mistura de etanol e água, na proporção de 70:30, por 1 hora, na velocidade máxima . The guarana powder was extracted on a mechanical stirrer with 4 liters of a mixture of ethanol and 70:30 water for 1 hour at full speed.
Em seguida, o produto obtido foi filtrado, em um funil de Buckner, obtendo-se a primeira fração intermediária . Then, the obtained product was filtered through a Buckner funnel, obtaining the first intermediate fraction.
0 resíduo da filtração foi, então, submetido à extração com 2 litros de etanol e água, na proporção de 70:30, por 1 hora, na velocidade máxima. O produto obtido foi filtrado, também em um funil de Buckner, obtendo-se a segunda fração intermediária. The filter residue was then extracted with 2 liters of 70:30 ethanol and water for 1 hour at full speed. The obtained product was filtered, also in a Buckner funnel, obtaining the second intermediate fraction.
As duas frações intermediárias foram misturadas e submetidas a secagem em um rotaevaporador, obtendo-se cerca de 500 gramas da fração ativa de acordo com a presente invenção . The two intermediate fractions were mixed and dried on a rotary evaporator, yielding about 500 grams of the active fraction according to the present invention.
QUANTIFICAÇÃO DOS TEORES DE TEOBROMINA E CAFEÍNA QUANTIFICATION OF THEOBROMINE AND CAFFEINE CONTENT
As 500 gramas da fração ativa de acordo com a presente invenção foram submetidas à análise por HPLC (High- performance liquid chromatography) para determinação dos teores de teobromina e cafeína. The 500 grams of the active fraction according to the present invention was subjected to HPLC analysis (High Performance Liquid Chromatography) to determine the theobromine and caffeine contents.
A curva analítica foi preparada pesando-se cerca de 10 mg dos padrões analíticos de teobromina e cafeína em balões volumétricos de 25 mL e avolumando-se com a fase móvel. A partir destas soluções estoque, foram feitas diluições sucessivas para construção da curva analítica para os padrões, filtradas em membrana de 0,45 μτα e injetar em cromatógrafo . The analytical curve was prepared by weighing about 10 mg of the theobromine and caffeine analytical standards in 25 mL volumetric flasks and bulging with the mobile phase. From these stock solutions, successive dilutions were made to construct the analytical curve for the standards, filtered through 0.45 μτα membrane and injected into a chromatograph.
As amostras foram preparadas pesando-se analiticamente cerca de 50mg da amostra em balão volumétrico de 25mL e completando-se o volume com a fase móvel, filtrando-se em membrana de 0,45μηα e injetandoOse no cromatógrafo . The samples were prepared by analytically weighing about 50mg of the sample in a 25mL volumetric flask and completing the volume with the mobile phase, filtering through 0.45μηα membrane and injecting into the chromatograph.
As condições cromatográficas para análise de teobromina foram: - Sistema LC-DAD Waters Alliance composto por bomba 2695, forno para aquecimento de colunas, detector de arranjo de diodos 2996 e software Empower® (Empower Software Solutions, Inc, US) . The chromatographic conditions for theobromine analysis were: - Waters Alliance LC-DAD system consisting of 2695 pump, column heater, 2996 diode array detector and Empower ® software (Empower Software Solutions, Inc, US).
- Coluna: Atlantis dC-18 100x2, lmm 3]i com pré (35°C) - Column: Atlantis dC-18 100x2.1mm 3] i with pre (35 ° C)
- Eluente: 0,1% de ácido fórmico / metanol (95/5 v/v) - Eluent: 0.1% formic acid / methanol (95/5 v / v)
- Vazão: 0,25 ml/minuto - Flow rate: 0.25 ml / minute
- Detecção a 273 nm - Detection at 273 nm
- Volume injetado: 20 yL - Injected Volume: 20 yL
As condições cromatográficas para análise de cafeína foram: The chromatographic conditions for caffeine analysis were:
- Sistema LC-DAD Waters Alliance composto por bomba 2695, forno para aquecimento de colunas, detector de arranjo de diodos 2996 e software Empower®. - Waters Alliance LC-DAD system consisting of 2695 pump, column heater, 2996 diode array detector and Empower ® software.
- Coluna: NOVA PAK CN HP (150 x 3,9 x 4 μτ ) (30°C) - Column: NEW PAK CN HP (150 x 3.9 x 4 μτ) (30 ° C)
- Eluente: 2mM ácido fosfórico / metanol (95/5 v/v) - Eluent: 2mM phosphoric acid / methanol (95/5 v / v)
- Vazão: 0,8 ml/minuto - Flow rate: 0.8 ml / min
- Detecção a 273 nm - Detection at 273 nm
- Volume injetado: 10 L - Injected volume: 10 L
O teor médio de teobromina na amostra de fração ativa de acordo com a presente invenção foi de 0, 096% e o teor médio de cafeína foi de 16,16%. The average content of theobromine in the active fraction sample according to the present invention was 0.096% and the average caffeine content was 16.16%.
Deve-se compreender que as realizações descritas acima são meramente ilustrativas e que qualquer modificação ao longo delas pode ocorrer para um técnico no assunto. Consequentemente, a presente invenção não deve ser considerada limitada às realizações descritas no presente. It should be understood that the embodiments described above are illustrative only and that any modification thereto may occur to one of ordinary skill in the art. Accordingly, the present invention is not to be construed as limited to the embodiments described herein.
0 homem da técnica saberá prontamente avaliar, por meio dos ensinamentos contidos no texto e nos exemplos apresentados, vantagens da invenção e propor variações e alternativas equivalentes de realização, sem no entanto fugir ao escopo da invenção, conforme definido nas reivindicações anexas. The person skilled in the art will readily be able to assess, by the teachings contained in the text and the examples presented, advantages of the invention and to propose variations and equivalent alternatives, but without departing from the scope of the invention as defined in the appended claims.
Claims
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BR112015010750-8A BR112015010750B1 (en) | 2012-12-13 | 2012-12-13 | USE OF PAULLINIA CUPANA PRODUCT |
| PCT/BR2012/000514 WO2014089646A1 (en) | 2012-12-13 | 2012-12-13 | Use of products from paullinia cupana to prevent or treat hot flushes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/BR2012/000514 WO2014089646A1 (en) | 2012-12-13 | 2012-12-13 | Use of products from paullinia cupana to prevent or treat hot flushes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2014089646A1 true WO2014089646A1 (en) | 2014-06-19 |
Family
ID=50933607
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/BR2012/000514 Ceased WO2014089646A1 (en) | 2012-12-13 | 2012-12-13 | Use of products from paullinia cupana to prevent or treat hot flushes |
Country Status (2)
| Country | Link |
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| BR (1) | BR112015010750B1 (en) |
| WO (1) | WO2014089646A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020115475A1 (en) * | 2018-12-04 | 2020-06-11 | Phytoquest Limited | Bioactive phytochemicals in zizyphus and guarana |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012129629A1 (en) * | 2011-03-31 | 2012-10-04 | Luiz Francisco Pianowski | Active fraction of paullinia cupana with improved activity against fatigue, method for producing an active fraction, use, pharmaceutical composition, medicament and method for the treatment of fatigue |
-
2012
- 2012-12-13 BR BR112015010750-8A patent/BR112015010750B1/en not_active IP Right Cessation
- 2012-12-13 WO PCT/BR2012/000514 patent/WO2014089646A1/en not_active Ceased
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012129629A1 (en) * | 2011-03-31 | 2012-10-04 | Luiz Francisco Pianowski | Active fraction of paullinia cupana with improved activity against fatigue, method for producing an active fraction, use, pharmaceutical composition, medicament and method for the treatment of fatigue |
Non-Patent Citations (3)
| Title |
|---|
| BLAES, AH ET AL.: "Nonpharmacologic complementary therapies in symptom management for breast cancer survivors.", SEMINARS IN. ONCOLOGY, vol. 38, no. 3, 2011, pages 394 - 402 * |
| CAMPOS, MPO ET AL.: "Effect of guarana (Paullinia cupana) on fatigue in breast cancer patients undergoing systemic chemotherapy.", JOURNAL OF CLINICAL ONCOLOGY, vol. 28, no. 15, 2010 * |
| SUCHSHINSKAYA, OY.: "The effect of body mass index, physical activity and caffeine consumption on hot flashes in hispanic women.", DISSERTAÇÃO DE MESTRADO EM DIETÉTICA. BALL STATE UNIVERSITY, 2012, Retrieved from the Internet <URL:http://cardinalscholar,bsu.edu/bitstream/123456789/195952/SuchshinskayaO_2012-2_BODY.pdf> * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020115475A1 (en) * | 2018-12-04 | 2020-06-11 | Phytoquest Limited | Bioactive phytochemicals in zizyphus and guarana |
Also Published As
| Publication number | Publication date |
|---|---|
| BR112015010750B1 (en) | 2021-06-01 |
| BR112015010750A2 (en) | 2017-07-11 |
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