BRPI0903057A2 - Clinical indication for herbal medicine extracted from artemisia artemisifolia, hatusima. for human infection with toxoplasma gondii - Google Patents
Clinical indication for herbal medicine extracted from artemisia artemisifolia, hatusima. for human infection with toxoplasma gondii Download PDFInfo
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- BRPI0903057A2 BRPI0903057A2 BRPI0903057A BRPI0903057A2 BR PI0903057 A2 BRPI0903057 A2 BR PI0903057A2 BR PI0903057 A BRPI0903057 A BR PI0903057A BR PI0903057 A2 BRPI0903057 A2 BR PI0903057A2
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- artemisia
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- 241000223997 Toxoplasma gondii Species 0.000 title abstract description 4
- 241000411851 herbal medicine Species 0.000 title abstract description 3
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Abstract
Indicação clínica de medicamento fitoterápico extraído de Artemisia artemisifolia, Hatusima. para a infecção humana por Toxoplasma gondii. Patente de Invenção para o tratamento da toxoplasmose referindo-se a uma segunda utilização (indicação clínica) do medicamento Artesunato originalmente Suíço extraído da Artemisia anua, importado e distribuído no país sob o nome comercial de Plasmotrin<32>, utilizado para tratamento de malária. Sua prescrição no Brasil está restrita as regiões endêmicas do Norte e Nordeste. Os medicamentos usados no tratamento da toxoplasmose não têm ação sobre o cisto e nem indicação para a fase crónica da infecção, ou seja, não há tratamento durante a fase latente do parasita. O tratamento considerado padrão para a toxopJasmose adquinda é a combinação de pirimetamina e as sulfonamidas que agem de maneira sinérgica sobre o metabolismo do acido fálico, atuando sobre as formas proliferativas do Toxo plasma gondu. Porém, devido à sua toxicidade, a eficácia terapêutica desta combinação pode ser seriamente limitada, pois estes fármacos causam efeitos colaterais expressivos (Lescano et aL, 2004). Espera-se com os ensaios experimentais e clínicos do Artesu nato, extraído da Artemisia ai-temisifolia de origem amazónica, a percepção do mecanismo de ação do composto fitoterápico nos bradizoítos e taquizoitos, formas latente e proliferativa do parasito que como a droga de referencia espera-se a redução da toxicidade em indivíduos imunossupnmidos ou sensibilidade à medicação administrada e também em crianças e mulheres grávidas, após comercialização do produto.Clinical indication of herbal medicine extracted from Artemisia artemisifolia, Hatusima. for human infection with Toxoplasma gondii. Patent of Invention for the treatment of toxoplasmosis referring to a second use (clinical indication) of the artisanal originally Swiss medicine extracted from Artemisia anua, imported and distributed in the country under the tradename Plasmotrin <32>, used for malaria treatment. Its prescription in Brazil is restricted to endemic regions of the North and Northeast. The drugs used to treat toxoplasmosis have no action on the cyst and no indication for the chronic phase of infection, ie there is no treatment during the latent phase of the parasite. The treatment considered standard for toxoplasmosis is the combination of pyrimethamine and sulfonamides that act synergistically on the metabolism of phallic acid acting on the proliferative forms of Toxo plasma gondu. However, due to their toxicity, the therapeutic efficacy of this combination may be seriously limited, as these drugs cause significant side effects (Lescano et al, 2004). It is expected with the experimental and clinical trials of Artesu nato, extracted from Artemisia ai-temisifolia of Amazonian origin, the perception of the mechanism of action of the phytotherapic compound on bradyzoites and tachyzoites, latent and proliferative forms of the parasite that as the reference drug expects. Reduction of toxicity in immunosuppressed individuals or sensitivity to the medication administered and also in children and pregnant women after commercialization of the product.
Description
Indicação clínica de medicamento fitoterápico extraído de Artemisiaartemisifoíia, Hat«s*ma. para a tafe*»» humana po. ToxoplasmaClinical indication for herbal medicine extracted from Artemisiaartemisiphoia, Hat 's * ma. for human tafe * »» po. Toxoplasma
A presente patente refere-se a uma segunda utilização (indicação cl.n.ca)de medicamento para a infecção por Toxopfasma gondii, de origem Suíça,importado e distribuído no país sob o nome comercial de Plasmotnn®, jaconsagrado para tratamento de malária. Sua prescrição no Brasil está restntaas regiões endêmicas do Norte e Nordeste.The present patent relates to a second use (cl.n.ca) of a drug for the infection by Toxopfasma gondii, of Swiss origin, imported and distributed in the country under the tradename Plasmotnn®, hybrids for malaria treatment. Its prescription in Brazil is in the endemic regions of the North and Northeast.
O tratamento clássico considerado padrão para a toxoplasmose adqu.ndaé a combinação de pirimetamina e as sulfonamidas que agem de maneirasinérgica sobre o metabolismo do ácido fólico, atuando sobre as formasproliferativas do Toxoplasma gondii. No entanto, devido à sua toxiadade, aeficácia terapêutica desta combinação pode ser seriamente limrtada,principalmente nos imunodeprimidos, pois estes fármacos causam d.sturb.oscolaterais expressivos (Lescano et al„ 2004).The classic treatment considered standard for toxoplasmosis is the combination of pyrimethamine and sulfonamides that act in anergic manner on folic acid metabolism, acting on the proliferative forms of Toxoplasma gondii. However, due to its toxicity, the therapeutic efficacy of this combination can be seriously limited, especially in immunocompromised patients, as these drugs cause significant side effects (Lescano et al „2004).
Os medicamentos usados no tratamento da toxoplasmose não têm açãosobre o cisto e nem indicação para a fase crônica da infecção, ou seja, não hátratamento durante a fase íafeníe do parasita.The drugs used in the treatment of toxoplasmosis have no action on the cyst and no indication for the chronic phase of infection, ie no treatment during the parasitic phase of the parasite.
A infecção aguda pós-natal nos indivíduos imunocompetentes é quasesempre subctfnica, não sendo tratada, por quase não ser diagnosticada. Noentanto, embora o quadro clínico seja normalmente de forma autolimitante aterapêutica tem importância por diminuir a ocorrência de lesões ocularesfuturas (Coutinho e Vergara, 2005).Acute postnatal infection in immunocompetent individuals is almost always sub-technical and untreated because it is almost undiagnosed. However, although the clinical picture is usually self-limiting atherapeutic, it is important to reduce the occurrence of future ocular lesions (Coutinho and Vergara, 2005).
Existem outros medicamentos utilizados com bastante freqüência notratamento da toxoplasmose. Entre eles: espiramicina, clindamicina,azitromicina, fansidar, mepron, daraprim e maloride, citados:There are other medicines that are used quite often for toxoplasmosis treatment. Among them: spiramycin, clindamycin, azithromycin, fansidar, mepron, daraprim and maloride, cited:
A espiramicina que é capaz de prolongar a vida de ratos inoculados comdoses tão elevadas de T. gondii que seriam mortais, tornando-osconvalescentes. Esta atua na porção 50S do ribossoma, impedindo a ação doRNA mensageiro, inibindo a síntese protéica do parasito.Spiramycin that is capable of extending the life of mice inoculated with such high doses of T. gondii that they would be deadly, making them convalescent. It acts on the 50S portion of the ribosome, preventing the action of the messenger RNA, inhibiting the protein synthesis of the parasite.
Tanyüskel et al. (2005) relatam que a azitromicina e a roxitromicinatambém podem ser eficazes no tratamento da toxoplasmose, sendo que estaúltima tem um efeito mais forte do que a primeira. A azitromicina, cuja me.avida é prolongada e ocasiona menos efeitos adversos do que a eritromicina,em modelos de toxoplasmose aguda, só apresenta efeito moderado sobre ainfecção no cérebro; este droga também to eficaz Én vífro, porém não ín v/voTanyüskel et al. (2005) report that azithromycin and roxithromycin may also be effective in the treatment of toxoplasmosis, the latter having a stronger effect than the former. Azithromycin, whose life span is prolonged and causes less adverse effects than erythromycin, in acute toxoplasmosis models, has only moderate effect on brain infection; this drug is also effective Is vifro, but not in v / vo
contra bradizoítas intracísticos (Derouin, 1995).against intracystic bradyzoites (Derouin, 1995).
Outras drogas empregadas são o tnmetopnm (em combinação com asulfa e o ácido folínico) e a clindamicina (Dubey e Beattie, 1988). Aclindamicina possui mecanismo de ação na síntese protéica, ao unir-se asubunidade 50S dos ribossomas.Other drugs employed are tromethamine (in combination with asulfa and folinic acid) and clindamycin (Dubey and Beattie, 1988). Aclindamycin has a mechanism of action in protein synthesis by joining the 50S subunit of ribosomes.
Pizzi em 1997, descreve que as Sulfamidas são quimioterápicosintroduzidos por Domagk em 1935. As Sulfapirimidinas são sulfamidas de açãoprolongada. São conhecidos entre outros,dois grupos que destacam-se notratamento da toxoplasmose: Sulfadimetoxina (2,6 - dimetoxi- pirimidilsulfanilamida) e Sulfametoxidiazina (5 - metoxi- 2 - perimidil sulfanilamida).Pizzi in 1997 describes Sulfamides as chemotherapeutic drugs introduced by Domagk in 1935. Sulfapyrimidines are long acting sulfamides. There are two known groups known for toxoplasmosis treatment: Sulfadimethoxine (2,6-dimethoxypyrimidylsulfanylamide) and Sulfamethoxydiazine (5-methoxy-2-perimidylsulfanylamide).
Estas suífamidas de ação prolongada por via oral. São bem absorvidas a nívelgastrointestinal. Atuam na via metabólica do ácido fólico, por competição dosubstrato com a enzima que transforma ácido paraaminobenzóico em ácidodihidropteróico.These long acting oral sulphamides. They are well absorbed at the gastrointestinal level. They act on the metabolic pathway of folic acid by competing the substrate with the enzyme that transforms paraaminobenzoic acid into dihydropteric acid.
A pirimetam/na, m vitro, inibe o cfescimento dos taquizoítos emconcentrações >0,05mg/L e é parasiticida. Em modelos murinos detoxoplasmose aguda tem mostrado atividade protetora, porém a suaacumulação nos tecidos é retardada, pelo que deve ser administrada emcombinação com suifonamidas ou outras drogas (Lescano, 2004).Pyrimethamine, in vitro, inhibits tachyzoite growth at concentrations> 0.05mg / L and is parasiticidal. In murine models acute detoxoplasmosis has shown protective activity, but its accumulation in tissues is delayed and should therefore be administered in combination with suifonamides or other drugs (Lescano, 2004).
As pirimetaminas agem como antimetabólitos do ácido fólico, necessáriopara a divisão nuclear do parasita". Distribuem-se em todos os órgãos,fundamentalmente no pulmão, baço, fígado, rins. Atravessa bem a barreirahematonuclear e se concentra na retina.Pyrimethamines act as folic acid antimetabolites, necessary for the nuclear division of the parasite. "They are distributed in all organs, mainly in the lung, spleen, liver, kidneys. It crosses the hematonuclear barrier and concentrates in the retina.
Para mulheres grávidas e indivíduos com deficiência do sistemaimunológico, o tratamento deve ser feito com pirimetamina, sulfadiazina e ácidofolínico durante quatro semanas. Clindamicina em adição a esses agentes éutilizada para tratamento da toxoplasmose ocular. Espiramicina é usada emgestantes para prevenir a infecção piacentána (Pizzi, 1984).For pregnant women and individuals with immune system deficiency, treatment should be done with pyrimethamine, sulfadiazine, and folic acid for four weeks. Clindamycin in addition to these agents is used for treating ocular toxoplasmosis. Spiramycin is used in pregnant women to prevent piacentána infection (Pizzi, 1984).
Nos casos de infecção fetai confirmada ou quando não puder ser afastadaa infecção fetat, o tratamento éfeito altemando-se dois esquemas terapêuticos.In cases of confirmed fetal infection or when fetal infection cannot be ruled out, treatment is effected by altering two therapeutic regimens.
Esquema I: Sulfadiazina 1g VO 6/6 horas + Pirimetamina 25mg VO1 x/dia + Ácido folínico 15mg em dias alternados VO 1x/dia;Scheme I: Sulfadiazine 1g VO 6/6 hours + Pyrimethamine 25mg VO1 x / day + Folinic acid 15mg every other day VO 1x / day;
e Esquema II: Espiramicina 1g VO de 8/8 horas por 4 semanas.and Scheme II: Spiramycin 1g VO 8/8 hours for 4 weeks.
O esquema I é contra-indicado no primeiro trimestre da gestação (só deveser iniciado após 20 semanas), não devendo também ser utilizado no últimomês, quando se deve optar pelo esquema Il (Chaves Neto, 2004).Scheme I is contraindicated in the first trimester of pregnancy (should only be started after 20 weeks) and should not be used in the last month, when schema Il should be chosen (Chaves Neto, 2004).
A quimioterapia da toxoplasmose tem caráter, sobretudo supressivo,agindo sobre os toxoplasmas em fase proliferativa (taquizoítas), mas deixandofora de alcance os bradizoítas protegidos pelas formações cisticas (Pizzi,1997).The chemotherapy of toxoplasmosis is mainly suppressive, acting on toxoplasmas in the proliferative phase (tachyzoites), but leaving out of reach the bradyzoites protected by cystic formations (Pizzi, 1997).
Considerando-se que é reconhecida a importância dos produtos naturais,incluindo derivados de plantas, no desenvolvimento de modernas drogasterapêuticas (Caferto, 1997), torna-se relevante a pesquisa farmacoiógica e odesenvolvimento de drogas, não somente quando seus constituintes sãousados diretamente como agentes terapêuticos, mas também como matérias-primas para a síntese, ou modelos para compostos farmacologicamente ativosQNHO, 1998).Considering that the importance of natural products, including plant derivatives, in the development of modern drug therapies is recognized (Caferto, 1997), it becomes relevant to research pharmacology and drug development, not only when their constituents are directly used as therapeutic agents. , but also as raw materials for synthesis, or models for pharmacologically active compounds (NHHO, 1998).
Espera-se com estes ensaios a percepção do mecanismo de ação docomposto moterápico associado à droga de referência com expectativas deredução da toxicidade em indivíduos imunossuprimidos ou com certasensibilidade à medicação administrada e também em mulheres grávidas, apóscomercialização do produto.It is expected with these trials the perception of the mechanism of action of the drug therapy associated with the reference drug with expectations of toxicity reduction in immunosuppressed individuals or with certain sensitivity to the medication administered and also in pregnant women, after marketing of the product.
O artesunato é um produto obtido da planta Artemisia annua L de origemasiática, solúvel em água com propriedades químicas dos ésteres daartemisinina. Sua resposta no tratamento da malária é mais rápida e maiseficaz do que cloroquina e a mefloquina. Trata-se de composto eficaz notratamento na forma cerebral da doença incluindo nos pacientes com infecçãomulti-resistentes. No presente patente, o tratamento será feito com artesunatoextraído da planta de origem amazônica Artemisia artemisifolia e este deveráser por sete dias e não havendo contra indicação de uso com outrosantiparasitários. Após administração orai ou retal, o artesunato é rapidamenteabsorvido e atinge ao pico máximo de concentração em 30 a 60minutos. Suametabolização se faz no fígado e (cito cromo P450) e por esterasessangüíneas se bio transformando em dühidroartemisinina que também é efetivocontra os parasites. O tempo médio de eliminação (meia-vida) é deaproximadamente 30 minutos enquanto que o seu subproduto metabóiico é de45 minutos. Este se encontra ligado a proteínas plasmáticas e é inativado nofígado.Artesunate is a product obtained from the Artemisia annua L plant of origemasiatic, water soluble with chemical properties of daartemisinin esters. Its response to malaria treatment is faster and more effective than chloroquine and mefloquine. It is an effective compound in the brain form of the disease, including in multidrug-resistant patients. In the present patent, the treatment will be done with artesunate extracted from the Amazonian plant Artemisia artemisifolia and this should be for seven days and there is no contraindication to use with other antiparasitics. Following oral or rectal administration, artesunate is rapidly absorbed and reaches its peak concentration within 30 to 60 minutes. Its metabolism is done in the liver and (cyto chromium P450) and by blood steroids turning into dühydroartemisinin which is also effective against parasites. The average elimination time (half-life) is approximately 30 minutes while its metabolic byproduct is 45 minutes. It is bound to plasma proteins and is inactivated in the liver.
A posologia recomendada e objeto de investigação clínica é 400mg noprimeiro dia e nos dias subseqüentes até o sétimo dia 200mgJóia dose única.Crianças devem receber 10mg/Kg por dia enquanto que nos dias subseqüentes5mg/Kg por dia.The recommended dosage and subject of clinical investigation is 400mg on the first day and on subsequent days until the seventh day 200mg. Single dose jewelry. Children should receive 10mg / kg per day while on subsequent days5mg / kg per day.
Os efeitos indesejáveis para o tratamento da malária foram transitórios erestritos a alterações na quantidade de reticulócitos e neutrófilos e, em algunscasos aumento fugaz da transaminases. Como não se conhece bem os efeitosem gestantes, seu uso no primeiro trimestre da gravidez está restrito ao critériode risco e benefício no caso de manifestação encefálica provocada peloparasito.Undesirable effects for the treatment of malaria were transient restricted to changes in the amount of reticulocytes and neutrophils and in some cases a fleeting increase in transaminases. As the effects on pregnant women are not well known, their use in the first trimester of pregnancy is restricted to the criteria of risk and benefit in the case of parasite-induced brain manifestation.
Postula-se também na presente patente a utilização do artesunatoextraído da planta cultivada no Brasil para o tratamento da Toxoplasmose comrepercussões no sistema nervoso e globo ocular.It is also postulated in this patent the use of artesunate extracted from the plant grown in Brazil for the treatment of Toxoplasmosis with repercussions in the nervous system and eyeball.
Na primeira etapa está proposto o uso do medicamento Plasmotrim® emcomparação com o sai sõdico de artemmnina extraída de Artemisiaartemisifolia de origem amazônica, tanto em estudos pré-clinicos como emestudos clínicos.In the first stage, it is proposed to use the drug Plasmotrim® in comparison with the artemmine sodium extract extracted from Amazonian Artemisiaartemisifolia, both in preclinical studies and clinical studies.
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| BRPI0903057 BRPI0903057A2 (en) | 2009-03-25 | 2009-03-25 | Clinical indication for herbal medicine extracted from artemisia artemisifolia, hatusima. for human infection with toxoplasma gondii |
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| BRPI0903057 BRPI0903057A2 (en) | 2009-03-25 | 2009-03-25 | Clinical indication for herbal medicine extracted from artemisia artemisifolia, hatusima. for human infection with toxoplasma gondii |
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| CN108902968A (en) * | 2018-06-20 | 2018-11-30 | 北京刚地源弓形虫病医学研究院 | A kind of integration of drinking and medicinal herbs food addition formula and preparation method thereof for driving away toxoplasma |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108902968A (en) * | 2018-06-20 | 2018-11-30 | 北京刚地源弓形虫病医学研究院 | A kind of integration of drinking and medicinal herbs food addition formula and preparation method thereof for driving away toxoplasma |
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