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WO2023146123A1 - Composition destinée à la prévention ou au traitement de maladies inflammatoires comprenant un extrait composite d'ocimum basilicum, de cirsium nipponicum (max.) makino et d'aruncus dioicus en tant que principe actif - Google Patents

Composition destinée à la prévention ou au traitement de maladies inflammatoires comprenant un extrait composite d'ocimum basilicum, de cirsium nipponicum (max.) makino et d'aruncus dioicus en tant que principe actif Download PDF

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Publication number
WO2023146123A1
WO2023146123A1 PCT/KR2022/019994 KR2022019994W WO2023146123A1 WO 2023146123 A1 WO2023146123 A1 WO 2023146123A1 KR 2022019994 W KR2022019994 W KR 2022019994W WO 2023146123 A1 WO2023146123 A1 WO 2023146123A1
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Prior art keywords
preventing
inflammatory diseases
water
composition
pharmaceutical composition
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English (en)
Korean (ko)
Inventor
송석진
차미란
손주아
오별님
방상우
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Uscarepharm Co ltd
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Uscarepharm Co ltd
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    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • 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)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures
    • A61K2800/591—Mixtures of compounds not provided for by any of the codes A61K2800/592 - A61K2800/596

Definitions

  • the present invention Thai basil ( Ocimum basilicum ), water thistle ( Cirsium nipponicum (Maxim.) Makino), and snow horse riding ( Aruncus dioicus ) It relates to a composition for preventing or treating inflammatory diseases comprising a composite extract as an active ingredient.
  • Inflammation is a defense response of the body against infection from external infectious agents such as external physical and chemical stimuli, bacteria, fungi, viruses, and various allergens.
  • the inflammatory response is a part of the innate immune response, and during the inflammatory reaction, blood plasma accumulates at the inflammatory site to dilute the toxicity secreted by bacteria, blood flow increases, and symptoms such as erythema, pain, edema, and fever are accompanied.
  • Various biochemical phenomena are involved in this inflammatory response.
  • NOS nitric oxide synthase
  • COX cyclooxygenase
  • NOS there are three isomers of NOS: eNOS (endothelial NOS), nNOS (nerve NOS), and bacterial endotoxins such as LPS (lipopolysaccharide), IL-1 ⁇ , TNF- ⁇ , IL-6, IL-8, and IL-6.
  • eNOS endothelial NOS
  • nNOS nerve NOS
  • LPS lipopolysaccharide
  • IL-1 ⁇ IL-1 ⁇
  • TNF- ⁇ IL-6
  • IL-8 IL-6
  • iNOS inducible NOS
  • NO produced by eNOS or nNOS plays an important role in maintaining homeostasis in the human body by performing various physiological reactions related to blood pressure regulation, neurotransmission, learning, and memory. It is known to be involved in various inflammatory diseases such as transplant rejection, autoimmune diseases, and neuronal death.
  • COX enzyme has hydroperoxidase (HOX) activity along with COX function and synthesizes intermediates PGG 2 and PGH 2 from arachidonic acid. and thromboxane A 2 (thromboxane A2, TxA2).
  • HOX hydroperoxidase
  • thromboxane A 2 thromboxane A2, TxA2
  • COX-1 is constitutively expressed in most tissues
  • COX-2 is rapidly induced by inflammatory cytokines and plays an important role in the inflammatory response.
  • Bacterial endotoxins such as LPS (lipopolysaccharide) activate NF- ⁇ B, a transcription factor, by binding to TLR4 (toll-like receptor 4), and induce the expression of iNOS and COX-2 to induce NO, inflammatory cytokines, and PGE2. It secretes inflammatory mediators. Inflammatory cytokines such as NO, TNF- ⁇ , and IL-6, and PGE2 have been reported as important factors inducing an inflammatory response in arthritis, fibromyalgia, Sjogren's syndrome, and the like.
  • Non-steroidal anti-inflammatory drugs which are currently widely used as anti-inflammatory drugs, are known to cause serious side effects such as gastrointestinal disorders, liver disorders, and renal disorders. Therefore, there is a need to develop new drugs that have anti-inflammatory activity and have low side effects and are effective continuously.
  • An object of the present invention is Vietnamese basil ( Ocimum basilicum ), water thistle ( Cirsium nipponicum (Maxim.) Makino), and snow riding horse ( Aruncus dioicus )
  • a composition for preventing or treating inflammatory diseases comprising two or more extracts selected from the group consisting of as an active ingredient.
  • the present invention Thai basil ( Ocimum basilicum ), water thistle ( Cirsium nipponicum (Maxim.) Makino), and snow riding horse ( Aruncus diioicus ) It provides a pharmaceutical composition for preventing or treating inflammatory diseases comprising two or more extracts selected from the group consisting of as an active ingredient.
  • the present invention Thai basil ( Ocimum basilicum ), water thistle ( Cirsium nipponicum (Maxim.) Makino), and snow riding horse ( Aruncus dioicus ) It provides a health functional food composition for preventing or improving inflammatory diseases containing two or more extracts selected from the group consisting of as an active ingredient.
  • the present invention Thai basil ( Ocimum basilicum ), water thistle ( Cirsium nipponicum (Maxim.) Makino) and snow riding horse ( Aruncus dioicus ) It provides a cosmetic composition for preventing or improving inflammatory diseases comprising two or more extracts selected from the group consisting of as an active ingredient.
  • Figure 1 is a result of measuring the change in gastric mucosal PEG2 (Prostaglandin E2) concentration through treatment with a composite extract of Thai basil, water thistle, and snow-capped horsetail.
  • gastric mucosal PEG2 Prostaglandin E2
  • Figure 2 is the result of measuring the degree of TNF- ⁇ production in the gastric mucosal tissue through the treatment of the composite extract of Thai basil, water thistle and snow-capped horsetail.
  • Figure 3 is the result of measuring the degree of IL-6 production in the gastric mucosal tissue through the treatment of Thai basil, water thistle, and the composite extract of snow sage.
  • Figure 4 is a result of measuring the IL-6 inhibitory ability in skin fibroblasts of the composite extract of Thai basil, water thistle and snow horse riding.
  • Figure 5 is the result of measuring the MMP-1 inhibitory ability in skin fibroblasts of the composite extract of Thai basil, water thistle and snow horse riding.
  • the present invention Thai basil ( Ocimum basilicum ), water thistle ( Cirsium nipponicum (Maxim.) Makino), and snow riding horse ( Aruncus diioicus ) It provides a pharmaceutical composition for preventing or treating inflammatory diseases comprising two or more extracts selected from the group consisting of as an active ingredient.
  • the extract is a
  • the extract is characterized in that it is extracted with water, (C1 ⁇ C4) alcohol or a mixed solvent thereof, preferably extracted with water or 30% ethanol, but is not limited thereto.
  • the inflammatory diseases include acute and chronic gastritis, peptic ulcer, duodenitis, gastric ulcer, enteritis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, hepatitis, bronchitis, allergic rhinitis, asthma, chronic obstructive pulmonary disease, contact dermatitis, allergy Dermatitis atopic, anaphylaxis, seborrheic dermatitis, systemic lupus erythematosus, scleroderma, stomatitis, osteoarthritis, rheumatoid arthritis, neuritis, diabetic retinopathy, retinitis, macular degeneration, uveitis, conjunctivitis, ankylosing spondylitis, osteoarthritis, nephritis , nephritis, Sjogren's syndrome, autoimmune pancreatitis, periodontal disease, chronic pelvic inflammatory disease, endometritis,
  • the extract is characterized in that it has an anti-inflammatory effect through inhibition of IL-6 (Interleukin 6) and TNF- ⁇ (tumor necrosis factor- ⁇ ) activity.
  • IL-6 Interleukin 6
  • TNF- ⁇ tumor necrosis factor- ⁇
  • the extract is characterized in that it has an antioxidant effect through inhibition of catalase and SOD (superoxide dismutase) activity.
  • the extract is characterized in that it has a skin protection effect through inhibition of IL-6 (Interleukin 6) and MMP-1 (matrix metalloproteinase-1) activity.
  • IL-6 Interleukin 6
  • MMP-1 matrix metalloproteinase-1
  • the pharmaceutical composition of the present invention is prepared in a unit dose form or in a multi-dose container by formulating using a pharmaceutically acceptable carrier according to a method that can be easily performed by those skilled in the art. It can be prepared by incorporating into
  • the pharmaceutically acceptable carrier is one commonly used in formulation, and includes lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like.
  • the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, and the like, in addition to the above components.
  • the content of the additives included in the pharmaceutical composition is not particularly limited and may be appropriately adjusted within the range of content used in conventional formulations.
  • the pharmaceutical composition is an aqueous solution, suspension, emulsion, and the like for injection, pills, capsules, granules, tablets, creams, gels, patches, sprays, ointments, warning agents, lotions, liniment agents, pasta agents, and cataplasma agents. It may be formulated in the form of one or more external agents selected from the group consisting of
  • the pharmaceutical composition of the present invention may additionally contain pharmaceutically acceptable carriers and diluents for formulation.
  • pharmaceutically acceptable carriers and diluents include excipients such as starch, sugar, and mannitol, fillers and extenders such as calcium phosphate, cellulose derivatives such as carboxymethylcellulose and hydroxypropylcellulose, gelatin, alginates, and polyvinyl fibres.
  • binders such as rolidone, etc., lubricants such as talc, calcium stearate, hydrogenated castor oil and polyethylene glycol, disintegrants such as povidone, crospovidone, surfactants such as polysorbates, cetyl alcohol, and glycerol; don't
  • the pharmaceutically acceptable carrier and diluent may be biologically and physiologically compatible with the subject.
  • diluents include, but are not limited to, saline, aqueous buffers, solvents and/or dispersion media.
  • the pharmaceutical composition of the present invention may be administered orally or parenterally (eg, intravenous, subcutaneous, intraperitoneal or topical application) depending on the desired method.
  • parenterally eg, intravenous, subcutaneous, intraperitoneal or topical application
  • it may be formulated into tablets, troches, lozenges, aqueous suspensions, oily suspensions, powders, granules, emulsions, hard capsules, soft capsules, syrups or elixirs.
  • parenteral administration it may be formulated as an injection solution, suppository, powder for respiratory inhalation, aerosol for spray, ointment, powder for application, oil, cream, etc.
  • the dosage of the pharmaceutical composition of the present invention depends on the condition and weight of the patient, age, sex, health condition, dietary constitution specificity, the nature of the preparation, the severity of the disease, the administration time of the composition, the administration method, the administration period or interval, the excretion rate, And the range may vary depending on the type of drug, and may be appropriately selected by a person skilled in the art. For example, it may range from about 0.1 to 10,000 mg/kg, but is not limited thereto, and may be divided and administered once or several times a day.
  • the pharmaceutical composition may be administered orally or parenterally (eg, intravenous, subcutaneous, intraperitoneal or topical application) depending on the desired method.
  • the pharmaceutically effective amount and effective dose of the pharmaceutical composition of the present invention may vary depending on the formulation method, administration method, administration time and/or administration route of the pharmaceutical composition, and those skilled in the art may be able to use the desired treatment An effective dosage can be readily determined and prescribed.
  • Administration of the pharmaceutical composition of the present invention may be administered once a day, or may be divided and administered several times.
  • the “anti-inflammatory” means an effect of improving inflammation.
  • the “inflammation” is a mechanism for restoring and regenerating the damaged area when an invasion that causes any organic change such as physical action, chemical substance, bacterial infection, etc. is applied to a living body or tissue. Once stimulation is applied, histamine, Inflammation may be induced as vascular active substances such as serotonin, bradykinin, prostaglandin, HETE (hydroxyeicosatetraenoic acid), and leukotrienes are liberated to increase vascular permeability.
  • the “antioxidation” refers to an action of inhibiting oxidation.
  • oxidation promoters and antioxidants are in balance, but due to various factors, this balance is lost and tilted in the direction of promoting oxidation. , oxidative stress is induced in vivo, which can cause cell damage and pathological diseases.
  • the present invention Thai basil ( Ocimum basilicum ), water thistle ( Cirsium nipponicum (Maxim.) Makino), and snow riding horse ( Aruncus dioicus ) It provides a health functional food composition for preventing or improving inflammatory diseases containing two or more extracts selected from the group consisting of as an active ingredient.
  • the health functional food composition is characterized in that it is an inner beauty food.
  • the present invention can be generally used as a commonly used food.
  • the food composition of the present invention can be used as a health functional food.
  • health functional food refers to food manufactured and processed using raw materials or ingredients having useful functionalities for the human body in accordance with the Health Functional Food Act, and "functional” refers to food that is not related to the structure and function of the human body. It refers to intake for the purpose of obtaining useful effects for health purposes such as regulating nutrients or physiological functions.
  • the health functional food composition may include conventional food additives, and the suitability as the "food additive" is determined in accordance with the General Rules and General Test Methods of Food Additives approved by the Ministry of Food and Drug Safety, unless otherwise specified. It is judged according to the specifications and standards for the item.
  • Items listed in the "Food Additive Code” include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as dark pigment, licorice extract, crystalline cellulose, goyang pigment, guar gum, and mixed preparations such as sodium L-glutamate preparations, noodle-added alkali preparations, preservative preparations, and tar color preparations.
  • chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid
  • natural additives such as dark pigment, licorice extract, crystalline cellulose, goyang pigment, guar gum
  • mixed preparations such as sodium L-glutamate preparations, noodle-added alkali preparations, preservative preparations, and tar color preparations.
  • the food composition of the present invention can be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills and the like.
  • hard capsules can be prepared by mixing and filling a composition according to the present invention with additives such as excipients in a conventional hard capsule, and soft capsules contain the composition according to the present invention. It can be prepared by mixing with additives such as excipients and filling in a capsule base such as gelatin.
  • the soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative, and the like, if necessary.
  • prevention refers to all activities that inhibit or delay a disease by administering the composition according to the present invention.
  • treatment refers to all activities that improve or beneficially change the symptoms of a disease by administering the composition according to the present invention.
  • improvement means any action that improves the bad condition of a disease by administering or ingesting the composition of the present invention to a subject.
  • the present invention Thai basil ( Ocimum basilicum ), water thistle ( Cirsium nipponicum (Maxim.) Makino) and snow riding horse ( Aruncus dioicus ) It provides a cosmetic composition for preventing or improving inflammatory diseases comprising two or more extracts selected from the group consisting of as an active ingredient.
  • the cosmetic composition includes skin lotion, skin softener, skin toner, astringent, milk lotion, moisture lotion, nutrient lotion, massage cream, nutrient cream, moisture cream, hand cream, foundation, essence, nutrient essence, pack, soap, cleansing foam, It is characterized in that it has one or more formulations selected from the group consisting of cleansing lotion, cleansing cream, body lotion and body cleanser, but is not limited thereto.
  • the cosmetic composition may be prepared in general emulsified and solubilized formulations.
  • cosmetic lotion such as softening lotion or nourishing lotion
  • emulsions such as facial lotion and body lotion
  • creams such as nourishing creams, moisture creams, and eye creams; essence; cosmetic ointment; spray; gel; pack; sunscreen; makeup base; foundations such as liquid type, solid type or spray type; powder
  • makeup removers such as cleansing creams, cleansing lotions, and cleansing oils
  • it may be formulated as a cleanser such as a cleansing foam, soap, body wash, etc., but is not limited thereto.
  • the external skin preparation may be formulated as an ointment, patch, gel, cream or spray, but is not limited thereto.
  • the cosmetic composition may be appropriately mixed with other components within a range that does not impair the purpose of the present invention depending on the type of formulation or purpose of use.
  • the cosmetic composition may include a conventionally acceptable carrier, and for example, oil, water, a surfactant, a moisturizer, a lower alcohol, a thickener, a chelating agent, a colorant, a preservative, a flavoring agent, and the like may be appropriately blended, but are not limited thereto. no.
  • the acceptable carrier may vary depending on the formulation.
  • animal oil, vegetable oil, wax, paraffin, starch, tracanthate, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or any of these as a carrier component when formulated into an ointment, paste, cream or gel extracts may be used.
  • lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder or extracts thereof may be used as a carrier component, and in the case of a spray, chlorofluorohydro It may further contain a propellant such as carbon, propane, butane or dimethyl ether.
  • a solvent, solubilizing agent, or emulsifying agent may be used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil may be used, and in particular, cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, fatty acid esters of glycerol, polyethylene glycol or sorbitan may be used.
  • a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tracanth and the like can be used.
  • the cosmetic composition is formulated as a soap, alkali metal salts of fatty acids, fatty acid hemiester salts, fatty acid protein hydrolyzates, isethionates, lanolin derivatives, fatty alcohols, vegetable oils, glycerol, sugars, etc. can be used
  • the cosmetic composition includes fatty substances, organic solvents, solubilizers, thickeners, gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, and fragrances commonly used in the industry depending on the quality or function of the final product. , surfactants, water, ionic or nonionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives commonly used in cosmetics It may additionally contain adjuvants commonly used in cosmetology or dermatology, such as any other ingredient.
  • the adjuvant and its mixing ratio may be appropriately selected so as not to affect desirable properties of the cosmetic composition according to the present invention.
  • LPS lipopolysaccharide
  • MTT 3-(4,5-dime thylthiazol-2-yl)-2,5-diphenyltetrazolium
  • DMSO dimethyl sulfoxide
  • Tumor necrosis factor (TNF)- ⁇ , IL-1 ⁇ , and IL-6 ELISA kits were purchased from Pierce Endogen (Rockford, IL., USA).
  • TNF Tumor necrosis factor
  • IL-1 ⁇ IL-1 ⁇
  • IL-6 ELISA kits were purchased from Pierce Endogen (Rockford, IL., USA).
  • special grade reagents were used, and measurements were performed using a UV/vis spectrophotometer (Hitachi, Japan), centrifuge (Hitachi, Japan), ELISA reader (Bio Rad, Japan), and the like.
  • Raw 264.7 cells a murine macrophage cell line, were purchased from ATCC (American Type Culture Collection), and Dulbecco's modified Eagle's medium (DMEM) was mixed with 10% fetal bovine serum (FBS), 100 U/mL penicillin, and 100 ⁇ g/mL streptomycin. 37 °C, 5% CO 2 was cultured in an incubator. During the experiment, the conditions of 80% confluency and less than 20 passages were observed, and the cells were cultured in a medium without FBS for 12 hours before the experiment.
  • DMEM Dulbecco's modified Eagle's medium
  • Nitric Oxide (hereinafter referred to as NO) was measured by measuring the amount of NO in the supernatant of cells as nitrite and nitrate.
  • the safe form after oxidation from nitrite to nitrate was measured using a grease reagent (Sigma, USA).
  • 500 ⁇ M of lipopolysaccharide (LPS) was added to all wells except for the normal group to stimulate them.
  • LPS lipopolysaccharide
  • the single or combined extracts of Examples 1 to 34 of Examples 1 to 34 were treated with 200 ⁇ g/mL concentration of Thai basil, snow sage, and water thistle, and then incubated for 24 hours.
  • the amount of NO production was measured by absorbance at 540 nm after collecting the supernatant over time and reacting by blocking light with a grease reagent for 20 minutes.
  • the NO inhibition rate was calculated according to the following formula.
  • Example NO inhibitory ability ( % )
  • Example NO inhibitory ability ( % )
  • LPS lipopolysaccharide
  • Example 29 to 31 showed high TNF- ⁇ inhibitory ability, and in particular, Example 30 showed the highest TNF- ⁇ inhibitory ability at 75.8% (Table 3).
  • Example TNF - ⁇ inhibitory ability ( % )
  • Example TNF - ⁇ inhibitory ability ( % )
  • Examples 25 to 34 a comparative experiment was conducted for NO and TNF- ⁇ inhibition rate by changing the extraction solvent.
  • the extraction solvent conditions and the weight ratio of the three composite extracts were set as shown in Table 4 to prepare Comparative Examples 1 to 30.
  • the water extract (Examples 25 to 34) showed superior NO and TNF- ⁇ inhibitory ability than the ethanol extract for each condition, and among the ethanol extracts, the 30% ethanol extract (Comparative Example 1 ⁇ 10) showed better inhibitory activity than other ethanol extraction conditions, and Comparative Example 6 showed 83.1% and 70.0% inhibitory activity, respectively, showing the best inhibitory activity among ethanol extracts (Table 4).
  • Seven-week-old female rats (Sprage-Dawley rats) were purchased from Coretech. The rats were placed in a rat cage at a temperature of 23 ⁇ 3 ° C, relative humidity of 55 ⁇ 15%, ventilation frequency of 10 to 20 times / hr, lighting time of 12 hours (8:00 am to 8:00 pm off), and illumination of 150 to 300 Lux. They were reared in a set room and fed a normal laboratory diet.
  • the area of the damaged area and the total area of the stomach on the mucosal surface of the lesion-prone gastric mucosa photographed with a digital camera were analyzed using ImageJ software (NIH, Bethesda, MD), and the Ulcer index (%) and gastritis inhibition rate were calculated. Ulcer index (%) and gastritis inhibition rate were calculated according to the following formula.
  • Gastritis inhibition rate ( % ) [ 1 - ( oral administration group ulcer index / Gastritis provoking group ulcer index)] X 100
  • a portion of the extracted stomach was cut to a certain weight, dissolved in RIPA buffer (Cell Signaling Technology, Danvers, MA, USA) to separate proteins, and then centrifuged for 10 minutes at 4°C and 13,000 ⁇ g in a centrifuge. Protein lysates were measured using a PGE2 ELISA kit (Cusabio Biotech, Wuhan, China).
  • Example 30 showed the highest value among all experimental groups including the positive control group at 140.9 pg/mg/protein (FIG. 1).
  • SOD activity was measured using the SOD assay kit (Biomax, Korea) according to the manufacturer's protocol, and in the other, the supernatant was centrifuged at 4°C and 10,000 rpm for 15 minutes, and then the CAT assay kit (Biomax, Korea) was used. ) was measured according to the manufacturer's protocol.
  • Example Thai basil Snow Riding water thistle SOD activity (U/g of protein)
  • Catalase activity (U/g of protein)
  • Vehicle 68.3 ⁇ 3.8 11.2 ⁇ 4.0 One One 80.6 ⁇ 5.5 19.5 ⁇ 2.2 2 One 82.1 ⁇ 5.1 20.5 ⁇ 3.4 3 One 83.7 ⁇ 4.0 16.8 ⁇ 2.6 25 One One One 97.5 ⁇ 7.1 21.5 ⁇ 3.5 29 One 2 One 99.1 ⁇ 3.7 22.4 ⁇ 4.0 30 One 4 One 116.9 ⁇ 5.7 30.4 ⁇ 3.5 31
  • One 6 One 104.5 ⁇ 4.6 25.5 ⁇ 1.5 Positive control group: Ayeop ethanol soft-textured extract 100.1 ⁇ 6.2 22.1 ⁇ 0.5
  • Examples 25, 29, 30 and 31 showed SDO and catalase activities similar to those of the positive control group, and in particular, Example 30 was a positive control group in both SOD and catalase activities. It was confirmed that it showed the highest activity among all experimental groups including (Table 6).
  • TNF- ⁇ and IL-6 in gastric mucosal tissue were measured. 100mM Tris-HCl (pH 7.4), 5mM Tris-HCl (pH 7.5), 2mM MgCl 2 , 15mM CaCl 2 , 1.5M sucrose and 0.1M DTT protease inhibitor cocktail were added to obtain cytoplasm from gastric tissue frozen in liquid nitrogen. After adding one buffer A and grinding with a tissue grinder (Bio Spec Product, USA), a 10% NP-40 solution was added. After standing on ice for 20 minutes, the supernatant containing cytoplasm was separated by centrifugation at 12,000 rpm for 2 minutes. TNF- ⁇ and IL-6 enzyme immunoassay (EIA) kit (RayBiotech, Norcross, GA, USA) were used to measure the supernatant. As a positive control group, ethanol soft extract was used.
  • EIA enzyme immunoassay
  • Example 25 showed lower TNF- ⁇ values than the positive control group, and among them, Example 30 showed the lowest value at 20.3 pg/mg/protein (Fig. 2).
  • Example 29 showed lower IL-6 values than the positive control group, and among them, Example 30 showed the lowest value at 107.7 pg/mg/protein (FIG. 3) .
  • CCD986sk a human skin fibroblast cell line
  • ATCC American Type Culture Collection
  • IMDM Iscove Modified Dulbecco Media
  • FBS fetal bovine serum
  • penicillin 100 U/mL penicillin
  • streptomycin 100 ⁇ g/mL streptomycin.
  • 37 °C, 5% CO 2 was cultured in an incubator.
  • the cells were cultured in a medium without FBS for 12 hours before the experiment in compliance with the conditions of 80% confluency and less than 10 passages.
  • IL-6 a pro-inflammatory cytokine
  • 1 ⁇ 10 6 cells were cultured for 24 hours and then stimulated by adding 20 ng/ml of TNF-a to all wells except for the normal group. After 1 hour, each well was treated with single or combined extracts of 200 ⁇ g/mL of Thai basil, snow sage, and water thistle, and then incubated for 24 hours.
  • the amount of IL-6 produced was measured by collecting the cell culture medium and using an IL-6 enzyme immunoassay (EIA) kit (R&D Systems Inc. Minneapolis, MN, USA) according to the manufacturer's protocol.
  • EIA enzyme immunoassay
  • Example 30 showed the lowest amount of IL-6 production among all experimental groups including the untreated group at 81.8% (FIG. 4).
  • MMP-1 matrix metalloproteinase-1
  • TNF-a matrix metalloproteinase-1
  • each well was treated with single or combined extracts of 200 ⁇ g/mL of Thai basil, snow sage, and water thistle, and then incubated for 24 hours.
  • the cell culture medium was collected and measured using the Human MMP1 ELISA Kit (Abcam, Cambridge, MA, USA) according to the manufacturer's protocol.
  • Example 30 showed the smallest amount of MMP-1 production at 101.3% (FIG. 5).

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Abstract

La présente invention concerne une composition destinée à la prévention ou au traitement de maladies inflammatoires comprenant un extrait composite d'Ocimum <i /> basilicum, de Cirsium nipponicum (Maxim.) Makino et d'Aruncus dioicus en tant que principe actif. Il a été confirmé que l'extrait composite obtenu par extraction des plantes médicinales à un rapport pondéral et dans des conditions d'extraction spécifiques présente un excellent effet anti-inflammatoire par rapport à des extraits uniques des plantes médicinales, et par conséquent, la composition peut être efficacement utilisée en tant que composition pharmaceutique, alicament fonctionnel ou composition cosmétique destinée à la prévention ou au traitement de maladies inflammatoires.
PCT/KR2022/019994 2022-01-26 2022-12-09 Composition destinée à la prévention ou au traitement de maladies inflammatoires comprenant un extrait composite d'ocimum basilicum, de cirsium nipponicum (max.) makino et d'aruncus dioicus en tant que principe actif Ceased WO2023146123A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120009554A (ko) * 2010-07-19 2012-02-02 웅진코웨이주식회사 항산화 및 항알레르기 효과를 갖는 허브 추출물 함유하는 화장료 조성물
JP2013514994A (ja) * 2009-12-18 2013-05-02 エクソドス ライフ サイエンシーズ リミテッド パートナーシップ 皮膚の炎症を治療するための方法及び組成物
KR101869353B1 (ko) * 2017-08-23 2018-06-21 재단법인 제주테크노파크 눈개승마 추출물에서 분리된 신규 화합물 및 이를 이용한 항염증 조성물
KR20210087405A (ko) * 2020-01-02 2021-07-12 주식회사 엘지생활건강 식물 추출물을 함유하는 조성물
KR20210087406A (ko) * 2020-01-02 2021-07-12 주식회사 엘지생활건강 식물 추출물을 함유하는 조성물

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013514994A (ja) * 2009-12-18 2013-05-02 エクソドス ライフ サイエンシーズ リミテッド パートナーシップ 皮膚の炎症を治療するための方法及び組成物
KR20120009554A (ko) * 2010-07-19 2012-02-02 웅진코웨이주식회사 항산화 및 항알레르기 효과를 갖는 허브 추출물 함유하는 화장료 조성물
KR101869353B1 (ko) * 2017-08-23 2018-06-21 재단법인 제주테크노파크 눈개승마 추출물에서 분리된 신규 화합물 및 이를 이용한 항염증 조성물
KR20210087405A (ko) * 2020-01-02 2021-07-12 주식회사 엘지생활건강 식물 추출물을 함유하는 조성물
KR20210087406A (ko) * 2020-01-02 2021-07-12 주식회사 엘지생활건강 식물 추출물을 함유하는 조성물

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