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WO2018039755A1 - Formulation pharmaceutique à base de zinc et de quercétine pour la production d'un médicament antiviral efficace contre la dengue et zika - Google Patents

Formulation pharmaceutique à base de zinc et de quercétine pour la production d'un médicament antiviral efficace contre la dengue et zika Download PDF

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WO2018039755A1
WO2018039755A1 PCT/BR2016/050220 BR2016050220W WO2018039755A1 WO 2018039755 A1 WO2018039755 A1 WO 2018039755A1 BR 2016050220 W BR2016050220 W BR 2016050220W WO 2018039755 A1 WO2018039755 A1 WO 2018039755A1
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quercetin
zinc
dengue
production
agents
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Portuguese (pt)
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William Abrão SAAD
Dong Hui Park
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to compositions for the prevention or treatment of symptoms of Flavivirus infections, such as Dengue.
  • the compositions comprise a combination of zinc compound, which may be chelated and / or non-chelated with the quercetin flavonoid or analogs and derivatives thereof, and other components may be formulated according to indication, age group, presentation form, pathologies. and weight.
  • Antiviral activity is achieved through the synergistic effect of quercetin and zinc that act through different mechanisms of action, preventing the virus from creating resistance mechanisms.
  • the present invention is in the field of pharmacy, notably where they may be produced for use in the following PHARMACEUTICAL FORM: ORAL in Capsules: may be hard, soft or gelatinous, tablets: may be coated or uncoated, dredged, filmed and still dispersive, Syrups, Solutions, Suspensions, Emulsions and Gel Solutions.
  • INJECTABLE Ampoule, Ampoule, saline and glucose.
  • TOPIC Ointment, Cream, Paste, Powder and Gel and even micro and nano structures can be used.
  • INHALATION Spray and nebulizer.
  • the influenza virus is known because of worldwide epidemics and pandemics. Despite many studies on these viruses, the true mechanism involved in the pathogenesis is still unclear. Major symptoms include extensive bleeding, hair cell epithelial necrosis, lymphoid cell infiltration, and alveolar space edema. Several studies have suggested that an excessive reaction of the host immune system may be responsible for these pathological effects. Neutrophil and macrophage accumulation in the lungs may play a role in the development of the disease as they produce reactive oxygen species such as superoxide ions (02) and hydrogen peroxide (H2O2), which in turn causes tissue damage, by right oxidation of cell biomolecules including lipids, proteins and nucleic acids or by activating certain nucleases or proteases.
  • reactive oxygen species such as superoxide ions (02) and hydrogen peroxide (H2O2)
  • Dengue and ZIKA is currently the most prevalent arbovirus in the world and is caused by Flaviruses transmitted by the Aedes aegypti and Aedes albopictus mosquitoes (TALARICO et al., 2007).
  • Flaviruses transmitted by the Aedes aegypti and Aedes albopictus mosquitoes (TALARICO et al., 2007).
  • TALARICO et al., 2007 TALARICO et al.
  • five antigenically related but distinct virus serotypes (DENV-1, 2, 3, 4 and 5) have been identified as belonging to the genus Flavivirus in the Flaviviradae family (KLAWIKKAN et al., 2011).
  • Zinc potentiates "in vitro” by ten times the antiviral action of IFN-alpha against rhinovirus, which highlights its synergistic action with the human organism in the fight against influenza (BERG ET AL, 2001).
  • Zinc inhibits respiratory syncytial virus, the leading cause of respiratory disease in children, once again demonstrating the importance of zinc for viral disease (SUARA AND CROWE, 2004).
  • Quercetin belongs to the class of flavonoids found in various foods including wine, broccoli, green tea, living, collard greens and onions.
  • Physiologist SzentGyorgyi discovered flavonoids in the 1930s, and they were quickly considered important in a range of plant processes, from pigmentation to protection against bacteria and fungi (CASTILLO ET AL, 1989).
  • quercetin is able to counteract the detrimental effects of oxidation. caused by reactive oxygen species in body cells (HARWOOD, 2007).
  • Quercetin is safe for human consumption and does not cause undesirable reactions in humans at high doses of several grams per day. Long-term animal toxicological studies have confirmed the safety of quercetin (HARWOOD, 2007).
  • Quercetin is a known antioxidant with antiviral and anti-inflammatory properties. Reactive oxygen species produced during viral infection, although necessary for effective virus clearance and inducing beneficial inflammatory process, can cause tissue damage if reactive oxygen species are overly or persistently produced. Antioxidant administration may therefore attenuate oxidative damage and susceptibility to secondary bacterial infections (CASTILLO ET AL., 1989). Studies suggest that quercetin not only eliminates free radicals, preventing tissue damage, but also decreases inflammatory markers such as IL-8, and exerts antiviral effects (KNAB ET AL., 2011).
  • quercetin acts as a potent antiviral agent by inhibiting viral replication of various respiratory, including influenza, parainfluenza, respiratory syncytial virus, adenovirus and rhinovirus (CHIANG et al, 2003 KAU L ET AL, 1985).
  • Quercetin may also exert an antiviral effect through its action on interferon and other proteins involved in the body's packaging and immune response. It may also increase the activity of various immune system components in fighting infections (ALVAREZ, 2006; NAIR, 2002).
  • Quercetin increases mitochondrial biogenesis in skeletal muscle, and thus could exert its antiviral effects by enhancing mitochondrial antiviral signaling. Quercetin showed inhibitory action on ⁇ -3-kinase, an enzyme necessary for viral endocytosis, and 3D RNA polymerase (pol) that is required for negative strand RNA production. Finally, there is also evidence that quercetin cleaves the elF4G protein, inhibiting viral genome translation, and may inhibit the PI-4 kinases required for viral replication in specialized lipid cell organelles (GANESAN ET AL, 2011).
  • quercetin reduces rhinovirus-induced expression of proinflammatory cytokines and lung inflammation in mice (GANESAN ET AL, 2011; GANESAN ET AL, 2012). Another study showed that quercetin reduced viral load and improved lung function in a rat model of chronic obstructive pulmonary disease. Quercetin supplementation reduced susceptibility to Influenza A virus infection and disease severity in rats (GONZALEZ-SEGOVIA et al., 2008), and reduced symptoms of upper respiratory tract infections in post-stress exercise athletes (NIEMAN ET AL, 2007).
  • an antiviral agent such as quercetin, which inhibits viral infection and replication in several stages without being specific to a single virus, and without serious side effects, may be more promising in treating common influenza (KINKER ET AL , 2014).
  • the present invention aims to present novel pharmaceutical formulations with antiviral activity which may be used in the treatment and prophylaxis of infections caused by dengue virus (Type II, II, III, IV and V), Zika virus and rotavirus, which may be produced for the human line: pediatric, adult, geriatric and also for veterinary use.
  • dengue virus Type II, II, III, IV and V
  • Zika virus Zika virus
  • rotavirus which may be produced for the human line: pediatric, adult, geriatric and also for veterinary use.
  • bioflavonoid kercetin including its analogs and derivatives, in combination with zinc, which may be in the form of salt or chelate, and other active ingredients.
  • antiviral or adjuvant action should be added according to indication, age group, presentation form, existing pathologies and weight.
  • the present invention aims to provide pharmaceutical formulations for the preparation of antiviral drug products used for both prophylaxis and treatment of symptoms caused by viral infections.
  • the pharmaceutical formulations presented herein have antiviral action for the following viruses: dengue (serotype I, serotype II, serotype III, serotype IV and serotype V), zika and rotavirus.
  • the present invention is based on the synergistic antiviral effect of two components, quercetin and zinc, enhancing final activity.
  • the synergistic effect occurs due to different mechanisms of action that can generally be characterized by resulting in inhibition and reduction of viral replication and not generating resistance, which is an important advantage of the formulation.
  • Quercetin and zinc antiviral mechanisms of action may occur by blocking endocytosis of the virus via PI-3 kinase, inhibiting and reducing viral replication at various stages, and in the early stages of viral replication.
  • inhibition occurs by reduction of viral RNA and DNA, either by inhibition of transcription, reserve transcription and translation, by direct action or by induction of high interferon-alpha production rates, in addition to increased mitochondrial antiviral response and inhibition of synthesis of heat shock protein and NS3 protease.
  • Anti-inflammatory activity is also considered by inhibiting NFkappa-beta by inducing A20 protein production. Inhibition of NFKappa-beta blocks the production of proinflammatory cytokines.
  • Bioflavonoid kercetin may be obtained either by synthesis or by vegetable extraction, including the extraction of glycosylated precursors which may be hydrolyzed to obtain it.
  • the use of bioflavonoid kercetin as one of the components of the pharmaceutical formulation of the present invention encompasses its analogues and derivatives, including salts, solvates, hydrates, prodrugs, isomers, including tautomers or stereoisomers which may be obtained by extractions. from plant sources, organic synthesis or semi-synthesis.
  • quercetin analogs and derivatives by way of example, but not restriction, are those having the sugar-associated aglycone moiety, or are methoxylated, sulfated or penylated derivatives at different positions of the hydroxyls.
  • Another embodiment of the present pharmaceutical composition is the combination of quercetin, or derivatives and analogs thereof, with zinc in the form of a complex, which may be in the quercetin: zinc (Q: Zn) ratio 1: 1; 1: 2; 1: 3; 2: 1; 2: 2; 2: 3 and others obtainable.
  • Zinc employed may be associated with quercetin in the form of complex or alone in the form of salts, semi-complexes or fully complexed with chelating components or agents such as amino acids, gluconate, EDTA, among others.
  • composition of the present invention may be administered alone or in combination with adjuvants and additives.
  • Adjuvant agents may be: water, stabilizing agents, solvents, buffer solutions, excipients, diluents, wetting agents, emulsifying agents, coating agents, preservatives, the mixture of which are all included.
  • Other adjuvants that may be applied are those responsible for the increased bioavailability and stability of quercetin, given its low bioavailability and stability in the body.
  • Some examples of such agents are rich citrus fruit extracts in vitamin C, such as the extracts of Acerola (Malpighia SP.) and Camu-camu (Myrciaria dubia), emulsifying agents that form microemulsions and nanoemualsions, as well as liposome forming agents, mannospheres, nanicapsules, nanoparticles and lipid complexes.
  • additives that may be used in the pharmaceutical formulation are colorants, sweeteners, antioxidant agents, thickening agents, preservatives, bleaching agents, bittering agents, flavoring agents and enzymes.
  • the routes of administration in which the present pharmaceutical formulation may be delivered are the oral routes, in capsule form, which may be hard, soft or gelatinous; in the form of tablets, whether or not coated, dredged, filmed; syrups, solutions, suspensions, emulsions and gel solutions.
  • parenterally in the form of ampoule, weak ampoule, saline and glycosylated.
  • the composition of the present INVENTION may be performed in various ways and for various pathologies.
  • it may be a pharmaceutical formulation for the prevention and treatment of dengue fever (serotype I, II, IV EV) and Zika which provides for the combination of zinc sulfate (300mg), quercetin (100mg) as loratadine antivirals (10mg) as antihistamine, caffeine (200 mg) as stimulant, soy lecithin as emulsifier and acetaminophen (800 mg) as antipyretic and analgesic for elaboration of a dose.
  • dengue fever serotype I, II, IV EV
  • Zika which provides for the combination of zinc sulfate (300mg), quercetin (100mg) as loratadine antivirals (10mg) as antihistamine, caffeine (200 mg) as stimulant, soy lecithin as emulsifier and acetaminophen (800 mg) as anti
  • the abovementioned quantities serve as a parameter for higher production, but are not limited to such formulation, dosage, concentration and this association of active ingredients.
  • the amounts used as well as the presentation may vary depending, for example, on the disorder or condition being treated or the physical states of the subject.
  • ALEXANDER S.P Flavonoids as antagonistsat Al adenosinereceptors. Phytother Res., V.20, p. 1009-1012, 2006.
  • ALVAREZ P. ALVARADO, C; PU ERTO, M, SCH LU MBERGER, A .; JIMENEZ, L .; DE LA FUENTE, M. Improvement of leukocyte functions in maturely aging mice after five weeks of dietary supplementation with polyphenol-rich cereals. Nutrition V. 22, p.913-921, 2006;
  • AVILA M. P .
  • BASTOS A.L.M .
  • FREITAS A. M .
  • ISAAC D.L.C .
  • R.V Retinopathy in a hepatitis C patient treated with pegylated interferon and ribavirin: case report.
  • Brazilian Archives of Ophthalmology S ⁇ o Paulo, v.69, n.2 mar./abr. 2006;
  • Normal plasma concentration is approximately 100 ⁇ g / dL and although only representing about 0.1C of body content, it is the primary source of this mineral for all cells, having a fast and rapid dynamics. under homeostatic control (Sandstron, 1997) as opposed to normal zinc values in the body.
  • Zinc is lost from the body through the kidneys, skin and intestines. Endogenous intestinal losses may range from 0.5 to 3.0mg / day. Under normal conditions, 95% of the zinc of the filterable plasma fraction is reabsorbed in the distal part of the renal tubule. Urinary losses range from 300-600mg / day, influenced by secretion mechanisms in the nephron proximal tubule (WHO, 2004).
  • the phytate content of foods reduces the bioavailability of Zn.
  • the phytate: Zn molar ratio of 20 may already have a negative effect because phytate is negatively charged; soon . It has a strong potential to bind bivalent cations, such as zinc, thus preventing its absorption (Zhouanderdman, 1995). The mere presence of nutrient in the diet does not guarantee its use by the body.
  • Quercetin flavonoid is an antioxidant commonly found in foods in glycosylated form, sometimes as -glycosidase. The nature of glycosylation is known to influence its absorption efficiency 8. Although quercetin-3-rutinoside is an important form of quercetin found in food, its availability is only 20% of quercetin-4'-glycoside. Quercetin-3-rutinoside can be transformed into quercetin-3-glycoside by breaking down the rhamnose molecule. Quercetin-3-glycoside and 4'-glycoside have high bioavailability.
  • quercetin-4'-glycoside Its peak plasma concentration is 5.0 +/- 1 mol / L quercetin-4'-glycoside, 4.5 +/- 0.7 mol / L.
  • the peak plasma concentration peak found for quercetin -3-glycoside was 37 +/- 12 min after ingestion, and 27 +/- 5 min after quercetin-4'-glycoside ingestion.
  • the plasma half-life of quercetin-3-glycoside is 18.5 +/- 0.8 h, while that of quercetin-4'-glycoside is 17.7 +/- 0.9 h. Glycosylated quercetin is more readily absorbed by humans, regardless of the position of glucose.
  • quercetininarutinoside Conversion of quercetininarutinoside to glycoside is an important strategy for increasing its bioavailability in foods 43. Consumption of polyphenol-rich foods, including flavonoids, their bioavailability and interfering factors has been widely studied. Intestinal absorption and metabolism of quercetin and other flavonoids are not fully elucidated at this time.
  • Unglycosylated flavonoids may be more easily absorbed by large intestine epithelial cells due to dualipophilicity that facilitates passage through the phospholipid layer of the cell membrane. Thus, these compounds enter the circulation and undergo methylation, glucuronidation and / or sulfation in the liver. A substantial part of this metabolite can then be excreted in the bile and returned to the intestinal lumen and hydrolyzed and resorbed by the intestinal cells, and excreted in feces41. Many studies report that Flavonoids in their free or glycosylated form are absorbed into the gastrointestinal tract and metabolised to conjugated glucuronidate or sulfate.
  • Quercetin is absorbed in the intestinal microflora and excreted in bile and urine as glucovoluntaries, hopronidate and conjugate sulfate within 48h. Subsequently, it is degraded by intestinal bacteria into phenolic acid, 3-hydroxyphenylacetic acid and 3,4-dihydroxyphenylacetic acid within ring B. Humans absorb considerable amounts of quercetin. In volunteer ileostomized patients. Hollman et al. 23 demonstrated that quercetinaglycosylated in onions was more absorbed than their aglycone strength. The authors suggest that the glucose transporter was responsible for the efficient transport of glycosylated quercetin by intestinal epithelial cells. The absorption of flavonoids by humans is controversial. Crespy et al. *, In an in situ perfusion study in the small intestine of rats, found that rutin was less absorbed than quercetin aglycone.
  • Rutin is preferably digested in the large intestine by the intestinal microflora, not in the small intestine. In humans, after periodic ingestion of glycosylated quercetin from onions, conjugated metabolites have accumulated in plasma 38.40. The maximum plasma level of quercetin was observed 8h after administration of aglycone51.
  • Quercetin absorption depends on the solubility of the vehicle used for its administration as it is insoluble in water. Piskula & Terao 46 observed that the absorption was faster when using the propylene glycol as a vehicle. In this case the maximum observed plasma level Alim. Nutr., Araraquara, v. 15, no. 3, p. 285-292,2004 287 was 30 me after its administration. Unlike other extrahepatic organs, such as the intestines and kidneys, the stomach is often overlooked as a metabolizing organ, although it is sometimes recognized as a site of absorption of different compounds.
  • glycosylated quercetin was not hydrolyzed and absorbed in the stomach, unlike its aglycone form which was partially absorbed by this tissue.
  • some processes such as the fermentation of grapes for wine production release the aglycone and glycosylated form which may result in a more efficient absorption of quercetin in the stomach.
  • Loratadine is a potent, long-acting tricyclic antihistamine with selective and antagonistic activity at peripheral H1 receptors. Loratadine is rapidly absorbed into the digestive tract after oral ingestion. Maximum plasma concentrations are reached within 1 hour and their half-life is 17 to 24 hours. Loratadine is metabolised in the liver intensively to decarboethoxyloratadine, which is metabolically active. Its binding to plasma proteins is 97% to 99% and that of the active metabolite is 73% to 76%. Renal insufficiency does not significantly modify the pharmacokinetics of loratadine. In case of hepatic impairment, pharmacokinetic parameters change; The dose of loratadine should be decreased. In elderly patients, there is no need to change the dose, as pharmacokinetic parameters do not change significantly. Paracetamol Brief Technical Information
  • Acetaminophen or acetaminophen is a drug with analgesic properties but no clinically significant anti-inflammatory properties. It acts by inhibiting the arachidonic acid cascade, preventing the synthesis of prostaglandins, pro-inflammatory cellular mediators, responsible for various manifestations of inflammation, such as the onset of pain.
  • This substance also has antipyretic effects. It is used in the following presentation forms: capsules, tablets, drops, syrups and injectables. It is currently one of the most used analgesics.
  • acetaminophen does not affect the gastric mucosa, does not alter blood clotting, and does not cause nephropathy.
  • Caffeine is classified by biochemistry as an alkaloid of the trimethylated xanthine group and is found in approximately 60 types of plants such as the leaves of various teas, cola (Cola acuminata), guarana [Paullinia cupana), coffee [Coffeaarabica) and cocoa [Theobromacacao). Caffeine acts on plants as natural pesticides protecting them from insects that feed on these plants.
  • Caffeine is absorbed in our body and reaches the bloodstream after 40 minutes to 2 hours of consumption, its absorption rate may be prolonged according to the presence of food in the gastrointestinal tract. Its metabolism occurs in the liver mainly by the action of the enzyme CYP1A2. After the first-pass effect, caffeine is rapidly distributed to all body tissues due to its high ability to cross membranes, including the placental and blood brain.
  • An average cup of coffee contains an average of 100 mg of caffeine. Already in a cup of tea or a glass of some sodas are forty milligrams of the substance. [127] Its rapid stimulating action makes it a powerful antidote to respiratory depression as a result of poisoning by drugs such as morphine and barbiturates. Excessive ingestion may cause some people negative effects such as irritability, anxiety, headache and insomnia.
  • Caffeine is found in many plant species, its function in the plant organism is to act as a natural pesticide species, high levels of caffeine are found in young seedlings that are still developing foliage but lack mechanical protection; Caffeine paralyzes and kills certain insects that feed on the plant.
  • the main plants containing the active ingredient caffeine are:
  • Lecithin is the name given to a mixture of glycolipids, triglycerides and phospholipids (eg phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol).
  • lecithin is commonly used as a synonym for pure phosphatidylcholine - a phospholipid which is the main component of the phosphate fraction obtained from egg yolk (from Greek: lekithos - ⁇ , from which it is derived). the name of the compost) or grain spills from where it is extracted by mechanical or chemical means using hexane.
  • Lecithin is marketed in high purity as a food supplement and for medical use.
  • lecithin In the event of a proper diet, the liver produces lecithin that will be used by the circulatory system and the nervous system. All cells in the body require lecithin, which is an essential unit of cell membrane structure. In fact, without this compound, the cell membrane would be rigid. It also acts to protect cells against oxidation.
  • soybean oil which is extracted from the flakes of its grains. From the oil, it is extracted through the vapor precipitation process.
  • Lecithin is used commercially as both emulsifier and lubricant in various economic activities, such as the pharmaceutical or food industry. For example, it is used as an emulsifier in chocolates and in the production of food coatings.
  • Lecithin is considered a non-toxic surfactant, well tolerated by the body, as it is an integral part of cell membranes and can be fully metabolized. It has been classified in the United States by FoodandDrugAdministration as generally recognized as a safe product for human consumption. Other emulsifiers are only excreted by the kidneys. Lecithin is recognized as a food additive by the European Union under the number E E322. [147] Studies indicate that soy lecithin has positive effects on the regulation of blood cholesterol and triglyceride levels.
  • Lecithin is a phospholipid found naturally in animal and plant foods, with egg yolk, soy and wheat germ as the main sources. Benefits of soy lecithin include cholesterol control, regulation of hormone production, regularization of menstruation, weight loss, minimization of menopausal symptoms, and headache combat. 121
  • soy lecithin When combined with a balanced diet and regular physical activity, soy lecithin can help with weight loss by speeding up metabolism and helping to break down fat.
  • Soy lecithin is also used in the food industry as an emulsifier, preventing water and fat from separating in food. It can be found in margarines, chocolates, cereals and baked foods.
  • Soy lecithin is a type of natural fat obtained during soybean oil production, and its main health benefits are due to the presence of choline, an important fat.
  • Figure 1 represents caffeine
  • Figure 2 represents soy lecithin
  • Figure 3 represents quercetin
  • Figure 5 represents loratadine
  • Figure 6 represents acetaminophen.

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Abstract

La présente invention concerne des compositions pour prévenir ou traiter les symptômes infectieux causés par flavivirus, notamment la dengue. Ces compositions comprennent une combinaison d'un composé de zinc pouvant être chélaté et/ou non chélaté avec le flavonoïde quercétine ou ses analogues et dérivés, d'autres composants pouvant en outre entrer dans la formulation selon l'indication, la tranche d'âge, la forme de présentation, les pathologies existantes et le poids. L'activité antivirale est atteinte au moyen de l'effet synergique de la quercétine et du zinc, qui agissent à travers différents mécanismes d'action, empêchant que le virus développe des mécanismes de résistance. La présente invention relève du domaine de la pharmacie, et permet notamment une production en vue d'une utilisation chez l'homme et l'animal dans les formes pharmaceutiques suivantes : Forme orale en capsule : peut être dure, molle ou gélatineuse, comprimé : peut être enrobé ou non, dragéifié, filmé ou encore dispersible, sirops, solutions, suspensions, émulsions et solutions en gel. Formes injectables : ampoule, flacon-ampoule, sérum physiologique et glycosylé. Forme topique : pommade, crème, pâte, poudre et gel, des micro-structures et des nano-structures pouvant en outre être utilisées. Forme inhalatoire : spray et nébuliseur.
PCT/BR2016/050220 2016-09-02 2016-09-05 Formulation pharmaceutique à base de zinc et de quercétine pour la production d'un médicament antiviral efficace contre la dengue et zika Ceased WO2018039755A1 (fr)

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CN110859833A (zh) * 2019-11-12 2020-03-06 中国医学科学院医药生物技术研究所 Zp10在制备以寨卡病毒蛋白酶为靶点的抗寨卡病毒药物中的应用
WO2021184070A1 (fr) * 2020-03-17 2021-09-23 Advance NanoTek Ltd. Composition antivirale de soins bucco-dentaires
WO2021216562A1 (fr) * 2020-04-21 2021-10-28 Finzi Eric Zinc pour le traitement de la covid-19

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