WO2021194436A1 - Composé antiviral et anti-inflammatoire naturel constitué de bioflavonoïdes qui sont extraits des pétales rouges de papaver rhoeas - Google Patents

Composé antiviral et anti-inflammatoire naturel constitué de bioflavonoïdes qui sont extraits des pétales rouges de papaver rhoeas Download PDF

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Publication number
WO2021194436A1
WO2021194436A1 PCT/TR2020/050242 TR2020050242W WO2021194436A1 WO 2021194436 A1 WO2021194436 A1 WO 2021194436A1 TR 2020050242 W TR2020050242 W TR 2020050242W WO 2021194436 A1 WO2021194436 A1 WO 2021194436A1
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WO
WIPO (PCT)
Prior art keywords
flavonoids
extracted
antiviral
papaver rhoeas
bioflavonoids
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PCT/TR2020/050242
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English (en)
Inventor
Gürer G. BUDAK
Mehmet BUDAK
Original Assignee
Nanobiomed Sağlik Ve Yaşam Bilimleri A. Ş.
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Application filed by Nanobiomed Sağlik Ve Yaşam Bilimleri A. Ş. filed Critical Nanobiomed Sağlik Ve Yaşam Bilimleri A. Ş.
Priority to PCT/TR2020/050242 priority Critical patent/WO2021194436A1/fr
Publication of WO2021194436A1 publication Critical patent/WO2021194436A1/fr

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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/66—Papaveraceae (Poppy family), e.g. bloodroot
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • This invention is a natural antiviral and anti-inflammatory compound that effects on SARS CoV-2 (Covid-19) and Influenza virus (H1N1, H5N1) consist of specific bioflavonoids which extracted from Papaver rhoeas red petals.
  • Flavonoids including chalcones, flavones, flavonols, anthocyanins and proanthocyanidins, are widely distributed in the plant kingdom and their metabolic pathways have been extensively studied using both biochemical and molecular techniques .
  • Flavonoid compounds derived from plants remain an important resource for the discovery and development of new antiviral drugs due to their expected low side effects and high availability in nature.
  • Coronaviruses are an etiologic agent of severe infections in both humans and animals, which can cause disorder not only in the respiratory tract but also in the digestive tract and systemically.
  • the new strain of CoV was identified at the end of 2019, initially named 2019- nCoV, and emerged during an outbreak in Wuhan, China. WHO named this CoV infections as COVID-19 (coronavirus disease 2019), on February 11, 2020.
  • COVID-19 coronavirus disease 2019
  • Some preliminary studies have investigated potential combinations that include the protease inhibitor lopinavir/ritonavir, which is commonly used to treat human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients, for the treatment of COVID-19-infected patients.
  • Other reported antiviral treatments form human pathogenic CoVs include nucleoside analogues, neuraminidase inhibitors, remdesivir, umifenovir (arbidol), tenofovir disoproxil (TDF), and lamivudine (3TC).
  • nelfmavir was identified as the best potential inhibitor against COVID-19 M protease.
  • nelfmavir and lopinavir may represent potential treatment options, and kaempferol, quercetin, luteolin-7- glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate were the most recommended flavonoid compounds that may act as potential inhibitors of COVID-19 Mpro.
  • Flavonoids have also been shown in a number of studies to be potent antioxidants, capable of scavenging hydroxyl radicals, superoxide anions, and lipid peroxyl radicals. Since the most important aspect in viral disease treatment is to inhibit virus replication, flavonoids as antiviral and antioxidant activities should be treatment of severe influenza-associated complications. Ueze and Toyoda used flavonoids compounds, such as 5,7,4-trihydroxy-8- methoxyflavone, catechins, quercetin 3-rhamnoside, isoquercetin and oligonol, possess both antiviral and antioxidant activities. In their theory, combination of these antioxidants with current anti-influenza drugs could improve conventional chemotherapy for severe influenza- associated complications.
  • Quercetin is a long lasting anti-inflammatory substance. This strong anti-inflammatory potential can be expressed on different cell types, both in animal and human models. It is known that Quercetin has both mast cell stabilizing and gastrointestinal cytoprotective activity. It can also play a modulating, biphasic and regulatory action on inflammation and immunity.
  • Papaver rhoeas is an annual herb indigenous to numerous regions in the world. The extracts of this plant have been used for the treatment of a wide range of diseases including inflammation, diarrhea, sleep disorders and, moreover, for cough, analgesia.
  • Kostic et all suggested to correlate with the antioxidant and antimicrobial (antibacterial) activity of the extracts of P. rhoeas L. from Southeast Portugal. BRIEF DESCRIPTION OF INVENTION
  • Bioflavonoids are seen as an important natural resource in the development of antiviral drugs. Flavonoids have also been shown in a number of studies to be powerful antioxidant-anti inflammatory agent that can remove hydroxyl radicals, superoxide anions and lipid peroxyl radicals.
  • Flavonoids are a large group of polyphenolic substances concentrated in many plants, seeds, fruits and flowers. Among the structural components of these molecules are two benzene rings on both sides of the 3 -carbon ring. The combination of more than one hydroxyl group, sugar, oxygen and methyl group attached to these structures creates several flavonoid such as anthocyanins, flavanols, flavanones, flavones, flavan-3-ols, and isoflavones.
  • Papaver rhoeas red petals have been used as herbal to treat some diseases in traditional medicine.
  • Various bioflavonoids and anthocyanins have been shown to be obtained by extraction of Papaver rhoeas red petals.
  • bioflavanoids obtained by extraction of Papaver rhoeas red petals on SARS CoV-2 (Covid-19) and Influenza virus (H1N1, H5N1) has not been previously described.
  • Present invention discloses an antiviral and anti inflammatory compound is formulated with specific flavonoids which extracted from Papaver rhoeas red petals.
  • Samples are mixed in an ultrasound bath for 6 h at room temperature and in darkness during the extraction procedure.
  • the mixture is filtered on a Buchner funnel and Whatman No. 1 filter paper.
  • the remaining solids are washed with solvent until a clear solution is obtained.
  • the filtrates are dried using a rotary evaporator at 30°C.
  • the concentrate is dissolved in 0.01% Acetic acid (v/v) in DW and the solution obtained is used for further purification.
  • Flavonoids a- In order to separate flavonoids, the total amount of extract crude is purified with Reverse Phase Chromatography technique in Preparative Process Chromatography (High- Performance Liquid Chromatography-HPLC). Other chromatographic separation techniques (such as normal phase, ion exchange, partition chromatography) are also be applied.
  • b- The C-18 separation column is used for Reverse Phase Chromatography. Mobile phase consist of methanol and distilled water with gradient elution applied. The flow rate is adjusted according to the column size, length and dimensions. At the end of the reverse phase, a specific chromatogram is obtained showing the UV peak intensities of the molecular structures in the crude extract.
  • c- The fractions of compounds are diluted with mobile phase because of elution nature. For that reason the mobile phase component is removed from original compound. Mobile phase elimination is performed with the Lyophilizator. Lyophilization is a stabilizing and drying process in which a substance is first frozen and then the quantity of the solvent is reduced. After sublimization (primary drying stage) and desorption (secondary drying stage), no further biological activation or chemical reactions occur in the purified compounds. At the end of lyophilization, the compounds also obtained as a solid substance with a high purity. d- Each purified fractions analyzed detailed to characterize and quantized the components. The confirmation and quantification of purified flavonoids are obtained by Quadrupole Time of Flight Mass Spectrometer (QTOF LC/MS).
  • QTOF LC/MS Quadrupole Time of Flight Mass Spectrometer
  • the specific bioflavonoids detected as a result of the HPLC and QTOF analysis are: Quercetin, Luteolin, Kaempferol, Apigenin, Quercitrin, Iso-quercetins, Cynaroside, Epicatechin, Epigallocatechin, and Hesperidin.
  • f- These falvanoids are used in the production of antiviral-anti-inflammatory compound.
  • the invention is related with Quercetin, Luteolin, Kaempferol, Apigenin, Quercitrin, Iso quercetins, Cynaroside, Epicatechin, Epigallocatechin, and Hesperidin flavonoids which extracted from Papaver rhoeas' red petals. Extracted flavonoids from Papaver rhoeas' red petals are used as natural antiviral and anti-inflammatory compound.
  • the flavonoids of the invention are in glycone (attached glycosyl group) and aglycone (lacking an attached glycosyl) form. The flavonoids are able to make covalent and coordinate bond with transition metals.
  • composition being in the form of oral and parenteral (intramuscular - intravenous) drug composition are prepared.
  • Pharmaceutical composition are in the form of oral food supplement.
  • Compounds are for use as a prophylactic and therapeutic antiviral and anti-inflammatory agent in infections caused by DNA and RNA viruses. And for use as prophylactic and therapeutic antiviral and anti-inflammatory agent in infections caused by coronaviruses (SARS, MERS, Covid-19) and Influenza Viruses (H5Nl-bird flu, H1N1 -swine flu).
  • Quadrupole Time of Flight Mass Spectrometer (QTOF LC/MS) data for Quercetin, Luteolin, Kaempferol, Apigenin, Quercitrin, Iso-quercetins, Cynaroside, Epicatechin, Epigallocatechin, and Hesperidin flavonoids extracted from Papaver rhoeas red petals are below.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Medical Informatics (AREA)
  • Virology (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Oncology (AREA)
  • Botany (AREA)
  • Communicable Diseases (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Les flavonoïdes, notamment les chalcones, les flavones, les flavonols, les anthocyanines et les proanthocyanidines, sont largement répandus dans le règne végétal et leurs voies métaboliques ont été largement étudiées en utilisant des techniques biochimiques et moléculaires. Les composés flavonoïdes dérivés de plantes restent une ressource importante pour la découverte et le développement de nouveaux médicaments antiviraux en raison de leurs faibles effets secondaires attendus et de leur disponibilité élevée dans la nature. La présente invention porte sur un composé antiviral et anti-inflammatoire naturel qui a des effets sur le SRAS CoV-2 (Covid-19) et le virus de la grippe (H1N1, H5N1) et qui est constitué de bioflavonoïdes spécifiques qui sont extraits des pétales rouges de Papaver rhoeas.
PCT/TR2020/050242 2020-03-26 2020-03-26 Composé antiviral et anti-inflammatoire naturel constitué de bioflavonoïdes qui sont extraits des pétales rouges de papaver rhoeas WO2021194436A1 (fr)

Priority Applications (1)

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PCT/TR2020/050242 WO2021194436A1 (fr) 2020-03-26 2020-03-26 Composé antiviral et anti-inflammatoire naturel constitué de bioflavonoïdes qui sont extraits des pétales rouges de papaver rhoeas

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PCT/TR2020/050242 WO2021194436A1 (fr) 2020-03-26 2020-03-26 Composé antiviral et anti-inflammatoire naturel constitué de bioflavonoïdes qui sont extraits des pétales rouges de papaver rhoeas

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021248254A3 (fr) * 2020-10-09 2022-03-10 Ingenew Pharma Inc. Doses pharmacothérapeutiques d'hespéridine ou de bioflavonoïdes apparentés pour faire face à des maladies infectieuses et/ou inflammatoires
CN115192566A (zh) * 2022-07-22 2022-10-18 刘倩 黄酮类单体化合物抗新型冠状病毒的应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2749287A1 (fr) * 2011-08-24 2014-07-02 Lotte Co., Ltd. Inhibiteur de l'infection par le virus de la grippe
WO2016064353A1 (fr) * 2014-10-21 2016-04-28 Budak Mehmet Formule de colorant de tissu et de cellule ayant une nouvelle molécule obtenue à partir de grand coquelicot
WO2019064255A1 (fr) * 2017-09-28 2019-04-04 Neilos S.r.l. Composition destinée à la prévention et/ou au traitement de troubles des voies respiratoires

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2749287A1 (fr) * 2011-08-24 2014-07-02 Lotte Co., Ltd. Inhibiteur de l'infection par le virus de la grippe
WO2016064353A1 (fr) * 2014-10-21 2016-04-28 Budak Mehmet Formule de colorant de tissu et de cellule ayant une nouvelle molécule obtenue à partir de grand coquelicot
WO2019064255A1 (fr) * 2017-09-28 2019-04-04 Neilos S.r.l. Composition destinée à la prévention et/ou au traitement de troubles des voies respiratoires

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HAJJAJ G ET AL.: "Analgesic and anti- inflammatory effects of Papaver rhoeas 1. a traditional medicinal plant of Morocco", JOURNAL OF NATURAL & AYURVEDIC MEDICINE, vol. 2, no. 7, pages 6, XP055861295 *
HILLENBRAND, M. ET AL.: "Depsides from the petals of Papaver rhoeas", PLANTA MEDICA, vol. 70, no. 04, 2004, pages 380 - 382, XP055603449, DOI: 10.1055/s-2004-818956 *
LEE, I. K. ET AL.: "Characterization of neuraminidase inhibitors in Korean Papaver rhoeas bee pollen contributing to anti-influenza activities in vitro", PLANTA MEDICA, vol. 82, no. 06, 2016, pages 524 - 529, XP018523625 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021248254A3 (fr) * 2020-10-09 2022-03-10 Ingenew Pharma Inc. Doses pharmacothérapeutiques d'hespéridine ou de bioflavonoïdes apparentés pour faire face à des maladies infectieuses et/ou inflammatoires
CN115192566A (zh) * 2022-07-22 2022-10-18 刘倩 黄酮类单体化合物抗新型冠状病毒的应用

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