WO2023128999A1 - Natural compounds with anti-inflammatory effect - Google Patents

Natural compounds with anti-inflammatory effect Download PDF

Info

Publication number
WO2023128999A1
WO2023128999A1 PCT/TR2022/051217 TR2022051217W WO2023128999A1 WO 2023128999 A1 WO2023128999 A1 WO 2023128999A1 TR 2022051217 W TR2022051217 W TR 2022051217W WO 2023128999 A1 WO2023128999 A1 WO 2023128999A1
Authority
WO
WIPO (PCT)
Prior art keywords
extract
purity
allicin
ramnoside
salvigenin
Prior art date
Application number
PCT/TR2022/051217
Other languages
French (fr)
Inventor
Ayşe Esra KARADAĞ
Fatma TOSUN
Sevde Nur BILTEKIN KALELI
Original Assignee
Istanbul Medipol Universitesi Teknoloji Transfer Ofisi Anonim Sirketi
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Istanbul Medipol Universitesi Teknoloji Transfer Ofisi Anonim Sirketi filed Critical Istanbul Medipol Universitesi Teknoloji Transfer Ofisi Anonim Sirketi
Publication of WO2023128999A1 publication Critical patent/WO2023128999A1/en

Links

Classifications

    • 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]
    • 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
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • A61K31/10—Sulfides; Sulfoxides; Sulfones
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • 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 
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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)
    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/288—Taraxacum (dandelion)
    • 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)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • 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)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8962—Allium, e.g. garden onion, leek, garlic or chives

Definitions

  • the present invention relates to plant extracts for use as anti-inflammatory agents and to pharmaceutical compositions comprising such plant extracts.
  • the inventors aim to develop anti-inflammatory agents derived from herbal or natural sources, which can be standardized in terms of the amount of pharmaceutically active substances contained therein.
  • the present invention relates to plant-derived agents for use as anti-inflammatory agents, characterized in that the plant-derived agent is selected from a group consisting of allicin, vitexin-o-2-ramnoside, malvin, chlorogenic acid, salvigenin and rosmarinic acid with at least 95% purity.
  • a preferred embodiment of the invention relates to plant-derived agents as active ingredients for use as anti-inflammatory agents, characterized in that the plant-derived agent is selected from a group consisting of allicin, vitexin-o-2-ramnoside, malvin, chlorogenic acid, salvigenin and rosmarinic acid with 95-99% purity.
  • a preferred embodiment of the invention relates to plant-derived agents as active ingredients for use as anti-inflammatory agents, characterized in that the plant-derived agent is selected from a group consisting of allicin, vitexin-o-2-ramnoside, malvin, chlorogenic acid, salvigenin and rosmarinic acid with 97-99% purity.
  • the amount of allicin or vitexin-o-2-ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid with % purity mentioned in the scope of the invention is determined by any method of analysis used in the determination of allicin or vitexin-o-2-ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid in the standardized agent, for example, HPLC and/or HPTLC device analysis, according to the Turkish Pharmacopoeia-II monographs (European pharmacopeia adaptation) - 2016 (Ministry of Health of Republic of Turkey, Turkish Medicines and Medical Devices Agency, I. Edition, 2016).
  • the ratio % mentioned in the context of the present invention is a relative ratio and refers to the amount of allicin or vitexin-o-2-ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid compared to the total amount of substance in the allicin or vitexin-o-2- ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid sample subjected to analysis.
  • the area of the entire peak obtained in the HPLC analysis of an allicin sample is expressed as 100, the area of the peak corresponding to allicin in the allicin sample according to the invention should be at least 95; this also applies to vitexin-o-2- ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid.
  • the invention relates to a plant-derived agent for use as an antiinflammatory agent, characterized in that the plant-derived agent is selected from an extract of Allium sativum onion comprising 0.4%-95% allicin, an extract of Malva sylvestris flower comprising 0.1%-95% malvin, an extract of Taraxacum officinale aboveground parts comprising l%-95% chlorogenic acid, an extract of Salvia triloba leaves comprising 0.1%- 95% salvigenin, an extract of Rosmarinus officinalis leaves comprising 0.5%-95% rosmarinic acid, vitexin-2-o-ramnoside with at least 95% purity.
  • the plant-derived agent is selected from an extract of Allium sativum onion comprising 0.4%-95% allicin, an extract of Malva sylvestris flower comprising 0.1%-95% malvin, an extract of Taraxacum officinale aboveground parts comprising l%-95% chlorogenic acid, an extract of Salvia triloba leaves comprising 0.1%- 95% salvigenin
  • a preferred embodiment of the invention relates to a plant-derived agent for use as an antiinflammatory agent, characterized in that the plant-derived agent is selected from an extract of Allium sativum onion comprising 0.4%-2% allicin, an extract of Malva Sylvestris flower comprising 0.1%-l% malvin, an extract of Taraxacum officinale aboveground parts comprising 0.1%-2% chlorogenic acid, an extract of Salvia triloba leaves comprising l%-5% salvigenin, an extract of Rosmarinus officinalis leaves comprising 0.5%-2% rosmarinic acid, vitexin-2-o-ramnoside with 95-99% purity.
  • the plant-derived agent is selected from an extract of Allium sativum onion comprising 0.4%-2% allicin, an extract of Malva Sylvestris flower comprising 0.1%-l% malvin, an extract of Taraxacum officinale aboveground parts comprising 0.1%-2% chlorogenic acid, an extract of Salvia triloba leaves comprising l%-5% salvigenin,
  • a natural anti-inflammatory agent is provided to patients with the anti-inflammatory agents according to the invention and pharmaceutical compositions obtained with such agents.
  • anti-inflammatory agent used here includes agents that show the effect as COX-1 and/or COX-2 and/or LOX inhibitors.
  • the invention relates to pharmaceutical compositions comprising allicin or vitexin-o-2-ramnoside or malvin or chlorogenic acid, or salvigenin or rosmarinic acid with at least 95% purity as an active ingredient suitable for use as an anti-inflammatory agent.
  • Another aspect of the invention is the use of another anti-inflammatory agent in addition to the said active ingredient in pharmaceutical compositions comprising allicin or vitexin-o-2- ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid with at least 95% purity, preferably 95-99% purity, in particular preferably 97-99% purity as the active ingredient.
  • said additional anti-inflammatory agents may be ibuprofen or diclofenac.
  • the invention in another aspect, relates to pharmaceutical compositions with antiinflammatory properties comprising an extract of Allium sativum onion comprising 0.4%- 95% allicin or an extract of Malva Sylvestris flower comprising 0.1%-95% malvin or an extract of Taraxacum officinale aboveground parts comprising 0.1%-95% chlorogenic acid or an extract of Salvia triloba leaves comprising 0.1%-95% salvigenin or an extract of Rosmarinus officinalis leaves comprising 0.5%-95% rosmarinic acid or vitexin-2-o- ramnoside with at least 95% purity.
  • the formulations mentioned here can be formulated with or without a second anti-inflammatory agent and can be selected from diclofenac and ibuprofen. Combinations according to the invention may be formulated in the same dosage form or different dosage forms.
  • the combination formulations according to the invention are formulated in different dosage forms, the said formulations may be used at different times or simultaneously or sequentially.
  • Formulations according to the invention may be formulated in a dosage form suitable for oral or topical use.
  • Oral formulations may be in any of the forms of tablet, capsule, extended- release capsule, delayed-release capsule, syrup, emulsion, suspension, coated tablet, layered tablet, orally disintegrating tablet, effervescent tablet, sachet, sublingual tablet.
  • Topical formulations may be in any of the forms of ointment, cream, gel, hydrogel, or lotion.
  • Formulations according to the invention may comprise at least one pharmaceutically acceptable excipient in addition to allicin.
  • Said excipient may not have any therapeutic effect but may be used to fulfill a requirement arising during the preparation or preservation or use of the formulation.
  • agents of natural origin suitable for use as anti-inflammatory agents have been developed.
  • the invention is of interest to both end-users in the healthcare sector and drug developers.
  • Example 1 IC50 values for COX-1 and COX-2 inhibition of allicin sample with at least 95% purity according to the invention and comparison thereof with known anti-inflammatory agents
  • the allicin sample used in the study whose results are given below comprises 95% allicin.
  • Example 2 IC50 values for COX-1 and COX-2 inhibition of vitexin-o-2-ramnoside sample with at least 95% purity according to the invention and comparison thereof with known antiinflammatory agents
  • vitexin-2-o-ramnoside sample used in the study whose results are given below comprises 95% vitexin-2-o-ramnoside.
  • Example 3 IC50 values for COX-1 and COX-2 inhibition of malvin sample with at least 95% purity according to the invention and comparison thereof with known anti-inflammatory agents
  • Malvin sample used in the study whose results are given below comprises 95% malvin.
  • Example 4 IC50 values for COX-1 and COX-2 inhibition of chi orogenic acid sample with at least 95% purity according to the invention and comparison thereof with known antiinflammatory agents
  • the chlorogenic acid sample used in the study whose results are given below comprises 95% chi orogenic acid.
  • Example 5 IC50 values for COX-1 and COX-2 inhibition of salvigenin sample with at least 95% purity according to the invention and comparison thereof with known anti-inflammatory agents
  • the Salvigenin sample used in the study whose results are given below comprises 95% salvigenin.
  • Example 6 IC50 values for COX-1 and COX-2 inhibition of rosmarinic acid sample with at least 95% purity according to the invention and comparison thereof with known antiinflammatory agents
  • the rosmarinic acid sample used in the study whose results are given below comprises 95% rosmarinic acid.
  • Example 1-6 When the results in Example 1-6 given above are evaluated, it is seen that the samples comprising at least 95% allicin or vitexin-o-2-ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid according to the invention show better or significantly close anti-inflammatory effect than anti-inflammatory agents used commercially for a long time, although it is a natural extract.
  • the anti-inflammatory effect mentioned here is shown through COX-1 and/or COX-2 inhibition.

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Engineering & Computer Science (AREA)
  • Botany (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pain & Pain Management (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Emergency Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Rheumatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The present invention relates to plant extracts for use as anti-inflammatory agents and to pharmaceutical compositions comprising such plant extracts.

Description

NATURAL COMPOUNDS WITH ANTI-INFLAMMATORY EFFECT
Field of the Invention
The present invention relates to plant extracts for use as anti-inflammatory agents and to pharmaceutical compositions comprising such plant extracts.
State of the Art
Diseases caused by inflammation are frequently encountered. Inflammations that occur in different parts of the body for different reasons are tried to be treated with various conventional drugs. However, treatment with these agents is sometimes inadequate and the discovery of novel and natural anti-inflammatory agents is of great importance.
One of the most common problems in the commercial use of therapeutic agents of natural origin is that the amount of pharmaceutically active substances in the extracts obtained from natural products is not constant. The variation in this amount, which may vary depending on the region or period of collection of the plant, prevents the development of reproducible and standardizable formulations using plant-based extracts.
Considering the state of the art, it is obvious that there is a need for anti-inflammatory agents that can be both obtained from herbal or natural sources and standardized in terms of the amount of substances that show pharmaceutical activity.
The Object of the Invention
The inventors aim to develop anti-inflammatory agents derived from herbal or natural sources, which can be standardized in terms of the amount of pharmaceutically active substances contained therein.
Brief Description of the Invention
The present invention relates to plant-derived agents for use as anti-inflammatory agents, characterized in that the plant-derived agent is selected from a group consisting of allicin, vitexin-o-2-ramnoside, malvin, chlorogenic acid, salvigenin and rosmarinic acid with at least 95% purity. Detailed Description of the Invention
A preferred embodiment of the invention relates to plant-derived agents as active ingredients for use as anti-inflammatory agents, characterized in that the plant-derived agent is selected from a group consisting of allicin, vitexin-o-2-ramnoside, malvin, chlorogenic acid, salvigenin and rosmarinic acid with 95-99% purity.
A preferred embodiment of the invention relates to plant-derived agents as active ingredients for use as anti-inflammatory agents, characterized in that the plant-derived agent is selected from a group consisting of allicin, vitexin-o-2-ramnoside, malvin, chlorogenic acid, salvigenin and rosmarinic acid with 97-99% purity.
The amount of allicin or vitexin-o-2-ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid with % purity mentioned in the scope of the invention is determined by any method of analysis used in the determination of allicin or vitexin-o-2-ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid in the standardized agent, for example, HPLC and/or HPTLC device analysis, according to the Turkish Pharmacopoeia-II monographs (European pharmacopeia adaptation) - 2016 (Ministry of Health of Republic of Turkey, Turkish Medicines and Medical Devices Agency, I. Edition, 2016).
The ratio % mentioned in the context of the present invention is a relative ratio and refers to the amount of allicin or vitexin-o-2-ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid compared to the total amount of substance in the allicin or vitexin-o-2- ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid sample subjected to analysis. For example, if the area of the entire peak obtained in the HPLC analysis of an allicin sample is expressed as 100, the area of the peak corresponding to allicin in the allicin sample according to the invention should be at least 95; this also applies to vitexin-o-2- ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid.
In another aspect, the invention relates to a plant-derived agent for use as an antiinflammatory agent, characterized in that the plant-derived agent is selected from an extract of Allium sativum onion comprising 0.4%-95% allicin, an extract of Malva sylvestris flower comprising 0.1%-95% malvin, an extract of Taraxacum officinale aboveground parts comprising l%-95% chlorogenic acid, an extract of Salvia triloba leaves comprising 0.1%- 95% salvigenin, an extract of Rosmarinus officinalis leaves comprising 0.5%-95% rosmarinic acid, vitexin-2-o-ramnoside with at least 95% purity. A preferred embodiment of the invention relates to a plant-derived agent for use as an antiinflammatory agent, characterized in that the plant-derived agent is selected from an extract of Allium sativum onion comprising 0.4%-2% allicin, an extract of Malva Sylvestris flower comprising 0.1%-l% malvin, an extract of Taraxacum officinale aboveground parts comprising 0.1%-2% chlorogenic acid, an extract of Salvia triloba leaves comprising l%-5% salvigenin, an extract of Rosmarinus officinalis leaves comprising 0.5%-2% rosmarinic acid, vitexin-2-o-ramnoside with 95-99% purity.
Furthermore, since there are not many agents that selectively inhibit COX and LOX enzymes, a natural anti-inflammatory agent is provided to patients with the anti-inflammatory agents according to the invention and pharmaceutical compositions obtained with such agents.
The term anti-inflammatory agent used here includes agents that show the effect as COX-1 and/or COX-2 and/or LOX inhibitors.
In another aspect, the invention relates to pharmaceutical compositions comprising allicin or vitexin-o-2-ramnoside or malvin or chlorogenic acid, or salvigenin or rosmarinic acid with at least 95% purity as an active ingredient suitable for use as an anti-inflammatory agent.
Another aspect of the invention is the use of another anti-inflammatory agent in addition to the said active ingredient in pharmaceutical compositions comprising allicin or vitexin-o-2- ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid with at least 95% purity, preferably 95-99% purity, in particular preferably 97-99% purity as the active ingredient. In one embodiment of the invention, said additional anti-inflammatory agents may be ibuprofen or diclofenac.
In another aspect, the invention relates to pharmaceutical compositions with antiinflammatory properties comprising an extract of Allium sativum onion comprising 0.4%- 95% allicin or an extract of Malva Sylvestris flower comprising 0.1%-95% malvin or an extract of Taraxacum officinale aboveground parts comprising 0.1%-95% chlorogenic acid or an extract of Salvia triloba leaves comprising 0.1%-95% salvigenin or an extract of Rosmarinus officinalis leaves comprising 0.5%-95% rosmarinic acid or vitexin-2-o- ramnoside with at least 95% purity. The formulations mentioned here can be formulated with or without a second anti-inflammatory agent and can be selected from diclofenac and ibuprofen. Combinations according to the invention may be formulated in the same dosage form or different dosage forms.
If the combination formulations according to the invention are formulated in different dosage forms, the said formulations may be used at different times or simultaneously or sequentially.
Formulations according to the invention may be formulated in a dosage form suitable for oral or topical use. Oral formulations may be in any of the forms of tablet, capsule, extended- release capsule, delayed-release capsule, syrup, emulsion, suspension, coated tablet, layered tablet, orally disintegrating tablet, effervescent tablet, sachet, sublingual tablet. Topical formulations may be in any of the forms of ointment, cream, gel, hydrogel, or lotion.
Formulations according to the invention may comprise at least one pharmaceutically acceptable excipient in addition to allicin. Said excipient may not have any therapeutic effect but may be used to fulfill a requirement arising during the preparation or preservation or use of the formulation.
Industrial Applicability
Thanks to the invention, agents of natural origin suitable for use as anti-inflammatory agents have been developed.
In this respect, the invention is of interest to both end-users in the healthcare sector and drug developers.
Examples
Example 1: IC50 values for COX-1 and COX-2 inhibition of allicin sample with at least 95% purity according to the invention and comparison thereof with known anti-inflammatory agents
The allicin sample used in the study whose results are given below comprises 95% allicin.
Figure imgf000005_0001
Figure imgf000006_0001
Example 2: IC50 values for COX-1 and COX-2 inhibition of vitexin-o-2-ramnoside sample with at least 95% purity according to the invention and comparison thereof with known antiinflammatory agents The vitexin-2-o-ramnoside sample used in the study whose results are given below comprises 95% vitexin-2-o-ramnoside.
Figure imgf000006_0002
Example 3: IC50 values for COX-1 and COX-2 inhibition of malvin sample with at least 95% purity according to the invention and comparison thereof with known anti-inflammatory agents
Malvin sample used in the study whose results are given below comprises 95% malvin.
Figure imgf000007_0001
Example 4: IC50 values for COX-1 and COX-2 inhibition of chi orogenic acid sample with at least 95% purity according to the invention and comparison thereof with known antiinflammatory agents The chlorogenic acid sample used in the study whose results are given below comprises 95% chi orogenic acid.
Figure imgf000007_0002
Example 5: IC50 values for COX-1 and COX-2 inhibition of salvigenin sample with at least 95% purity according to the invention and comparison thereof with known anti-inflammatory agents The Salvigenin sample used in the study whose results are given below comprises 95% salvigenin.
Figure imgf000007_0003
Figure imgf000008_0001
Example 6: IC50 values for COX-1 and COX-2 inhibition of rosmarinic acid sample with at least 95% purity according to the invention and comparison thereof with known antiinflammatory agents The rosmarinic acid sample used in the study whose results are given below comprises 95% rosmarinic acid.
Figure imgf000008_0002
When the results in Example 1-6 given above are evaluated, it is seen that the samples comprising at least 95% allicin or vitexin-o-2-ramnoside or malvin or chlorogenic acid or salvigenin or rosmarinic acid according to the invention show better or significantly close anti-inflammatory effect than anti-inflammatory agents used commercially for a long time, although it is a natural extract. The anti-inflammatory effect mentioned here is shown through COX-1 and/or COX-2 inhibition. Better COX-1 and COX-2 inhibition compared to ibuprofen and diclofenac, which have been frequently used anti-inflammatory agents in the pharmaceutical market for many years, and even celecoxib, indomethacin, SC-560, Dup-697 molecules, which have a strong anti-inflammatory effect suggests that these standardized pure components of natural origin are important anti-inflammatory agents.

Claims

1. A pharmaceutical composition comprising allicin, vitexin-o-2-ramnoside, malvin, chlorogenic acid, salvigenin, or rosmarinic acid with at least 95% purity, for use as an anti-inflammatory agent.
2. The composition according to claim 1, characterized in that it has 95-99% purity.
3. The composition according to any one of claims 1 or 2, characterized in that it has 97- 99% purity.
4. The pharmaceutical composition suitable for use as an anti-inflammatory agent, comprising an extract of Allium sativum onion comprising 0.4%-95% allicin or an extract of Malva Sylvestris flower comprising 0.1%-95% malvin or an extract of Taraxacum officinale aboveground parts comprising 0.1%-95% chlorogenic acid or an extract of Salvia triloba leaves comprising 0.1%-95% salvigenin or an extract of Rosmarinus officinalis leaves comprising 0.5%-95% rosmarinic acid or vitexin-2-o-ramnoside with at least 95% purity as active ingredients.
5. The pharmaceutical composition suitable for use as an anti-inflammatory agent according to claim 4, characterized in that it comprises an extract of Allium sativum onion comprising 0.4%-2% allicin, an extract of Malva Sylvestris flower comprising 0.1%-l% malvin, an extract of Taraxacum officinale aboveground parts comprising 0.1%-2% chlorogenic acid, an extract of Salvia triloba leaves comprising l%-5% salvigenin, an extract of Rosmarinus officinalis leaves comprising 0.5%-2% rosmarinic acid, vitexin-2- o-ramnoside with 95-99% purity.
6. The pharmaceutical composition according to any one of claims 1-5, characterized in that it comprises another anti-inflammatory agent selected from diclofenac or ibuprofen.
7. The pharmaceutical composition according to any one of claims 1-6, characterized in that it is formulated in a dosage form suitable for oral or topical use.
8
PCT/TR2022/051217 2021-12-28 2022-11-01 Natural compounds with anti-inflammatory effect WO2023128999A1 (en)

Applications Claiming Priority (12)

Application Number Priority Date Filing Date Title
TR2021021394 2021-12-28
TRTR2021/021389 2021-12-28
TRTR2021/021403 2021-12-28
TR2021021396 2021-12-28
TR2021021403 2021-12-28
TRTR2021/021396 2021-12-28
TR2021021389 2021-12-28
TRTR2021/021374 2021-12-28
TR2021021374 2021-12-28
TRTR2021/021394 2021-12-28
TR2021021379 2021-12-28
TRTR2021/021379 2021-12-28

Publications (1)

Publication Number Publication Date
WO2023128999A1 true WO2023128999A1 (en) 2023-07-06

Family

ID=87000153

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2022/051217 WO2023128999A1 (en) 2021-12-28 2022-11-01 Natural compounds with anti-inflammatory effect

Country Status (1)

Country Link
WO (1) WO2023128999A1 (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2729617A1 (en) * 2008-07-03 2010-01-07 Ying Yao A natural allicin tablet and preparation method thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2729617A1 (en) * 2008-07-03 2010-01-07 Ying Yao A natural allicin tablet and preparation method thereof

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
HWANG SU JUNG, KIM YONG-WAN, PARK YOHAN, LEE HYO-JONG, KIM KYU-WON: "Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells", INFLAMMATION RESEARCH, BIRKHAEUSER VERSLAG , BASEL, CH, vol. 63, no. 1, 1 January 2014 (2014-01-01), CH , pages 81 - 90, XP093078188, ISSN: 1023-3830, DOI: 10.1007/s00011-013-0674-4 *
JOAO ROCHA; MARIA EDUARDO‐FIGUEIRA; ANDREIA BARATEIRO; ADELAIDE FERNANDES; DORA BRITES; ROSARIO BRONZE; CATARINA MM DUARTE; ANA TE: "Anti‐inflammatory Effect of Rosmarinic Acid and an Extract of Rosmarinus officinalis in Rat Models of Local and Systemic Inflammation", BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, NORDIC PHARMACOLOGICAL SOCIETY, COPENHAGEN, DK, vol. 116, no. 5, 6 November 2014 (2014-11-06), COPENHAGEN, DK , pages 398 - 413, XP072368686, ISSN: 1742-7835, DOI: 10.1111/bcpt.12335 *
MANSOURABADI AMIR HOSSEIN, SADEGHI HAMID MOHAMMAD, RAZAVI NASTARAN, REZVANI EBRAHIM: "Anti-inflammatory and Analgesic Properties of Salvigenin, Salvia officinalis Flavonoid Extracted", ADVANCED HERBAL MEDICINE, vol. 2, no. 1, 1 January 2016 (2016-01-01), pages 31 - 41, XP093078187 *
NINFALI PAOLINO, ANTONINI ELENA: "Great nutraceutical potential of bioactive compounds from Beta vulgaris cicla and rubra", INTERNATIONAL JOURNAL ON NUTRACEUTICALS, FUNCTIONAL FOODS AND NOVEL FOODS, vol. 17, 1 January 2018 (2018-01-01), pages 75 - 81, XP093078189, DOI: 10.17470/NF-018-1002-2 *
SEDDIGHFAR MASOUD, MIRGHAZANFARI SAYID MAHDI, DADPAY MASOUMEH: "Analgesic and anti-inflammatory properties of hydroalcoholic extracts of Malva sylvestris, Carum carvi or Medicago sativa, and their combination in a rat model", JOURNAL OF INTEGRATIVE MEDICINE, KEXUE CHUBANSHE,SCIENCE PRESS, CN, vol. 18, no. 2, 1 March 2020 (2020-03-01), CN , pages 181 - 188, XP093078181, ISSN: 2095-4964, DOI: 10.1016/j.joim.2020.02.003 *

Similar Documents

Publication Publication Date Title
AU2003286549B2 (en) Compositions that treat or inhibit pathological conditions associated with inflammatory response
US7270835B2 (en) Compositions that treat or inhibit pathological conditions associated with inflammatory response
US8557306B2 (en) Compositions that treat or inhibit pathological conditions associated with inflammatory response
EP2221052A2 (en) Compositions that treat or inhibit pathological conditions associated with inflammatory response
McGregor et al. Devil’s claw (Harpagophytum procumbens): an anti-inflammatory herb with therapeutic potential
Abdou et al. Nephroprotective activity of Aframomum melegueta seeds extract against diclofenac-induced acute kidney injury: A mechanistic study
Mutia et al. Hepatoprotective effect of Citrus sinensis (L.) osbeck ethanol extract in paracetamol-induced rats
US7811610B2 (en) Anti-inflammatory pharmaceutical compositions for reducing inflammation and the treatment or prevention of gastric toxicity
WO2023128999A1 (en) Natural compounds with anti-inflammatory effect
US7807203B2 (en) Anti-inflammatory pharmaceutical compositions for reducing inflammation and the treatment or prevention of gastric toxicity
WO2023128989A1 (en) Inhibitory effects of standardized extracts of rosmarinus officinalis leaves on cox-1, cox-2 and lox enzymes
WO2023128987A1 (en) Inhibitory effects of standardized extracts of allium sativum l. onions on cox-1, cox-2 and lox enzymes
Alabdallat In-vivo antioxidant effects of the orally administered paracetamol, aqueous extracts of saliva triloba, and origanum syriacum
WO2023128991A1 (en) Inhibitory effects of standardized extracts of taraxacum officinale aerial parts on cox-1, cox-2 and lox enzymes
WO2023128990A1 (en) Inhibitory effects of standardized extracts of salvia triloba leaves on cox-1, cox-2 and lox enzymes
WO2023128988A1 (en) Inhibitory effects of standardized extracts of malva sylvestris flowers on cox-1, cox-2 and lox enzymes
WO2023128984A1 (en) Cox-1, cox-2 and lox enzyme inhibiting effects of standardized extracts of crataegus monoygna fruits and leaves with flowerleaves with flowers
TR2021021396A1 (en) INHIBITORY EFFECTS OF CHLOROGENIC ACID ON COX-1, COX-2 AND LOX ENZYMES
TR2021021403A1 (en) INHIBITORY EFFECTS OF VITEXIN-2-O-RAMNOSITE ON COX-1, COX-2 AND LOX ENZYMES
TR2021021374A1 (en) INHIBITORY EFFECTS OF ALLICIN ON COX-1, COX-2 AND LOX ENZYMES
TR2021021379A1 (en) INHIBITORY EFFECTS OF MALVIN ON COX-1, COX-2 AND LOX ENZYMES
TR2021021389A1 (en) INHIBITORY EFFECTS OF ROSMARINIC ACID ON COX-1, COX-2 AND LOX ENZYMES
TR2021021394A1 (en) INHIBITORY EFFECTS OF SALVIGENIN ON COX-1, COX-2 AND LOX ENZYMES
TR2021021375A2 (en) INHIBITORY EFFECTS OF STANDARDIZED EXTRACTS OF ALLIUM SATIVUM L. ONIONS ON COX-1, COX-2 AND LOX ENZYMES
TR2021021372A1 (en) INHIBITORY EFFECTS OF STANDARDIZED EXTRACTS OF CRATAEGUS MONOYGNA FRUITS AND FLOWERING LEAVES ON COX-1, COX-2 AND LOX ENZYMES

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22917002

Country of ref document: EP

Kind code of ref document: A1